Input: Transcriptional cooperation between p53 and NF-kappa B p65 regulates microRNA-224 transcription in mouse ovarian granulosa cells.


Input: MicroRNAs (miRNAs) have been indicated to play key roles in ovarian follicular development.


Input: However, little is known about how the miRNA gene expression itself is regulated in the mammalian ovary.


Input: We previously reported that miR-224 is involved in TGF-beta 1-mediated follicular granulosa cell (GC) growth and estradiol (E2) production by targeting Smad4.

estradiol


Input: Here, the transcriptional regulation of miR-224 expression in GCs was further investigated.


Input: Our results showed that both the tumor suppressor gene p53 and NF-kappa B p65 subunit suppressed the TGF-beta 1-induced increase in pri-miR-224 expression in GCs.


Input: ChIP assays demonstrated that TGF-beta 1 enhanced the binding of p53 and p65 to the proximal promoter region of GABAA receptor epsilon subunit (miR-224 host gene).


Input: p53 and p65 transcriptionally cooperated to inactivate the GABAA receptor epsilon subunit promoter.


Input: In addition, p53/p65 could up-regulate Smad4 expression by inhibiting its target miR-224 in GCs which contributed, at least partially, to the effects of miR-224 and Smad4 on GC proliferation and E2 release.


Input: Our results provide new data about the interplay between transcription factors involved in GC proliferation and function by cooperatively regulating miRNA expression.


Input: Inverted CdSe/CdS/ZnS quantum dot light emitting devices with titanium dioxide as an electron-injection contact.

CdSe

CdS

ZnS

titanium dioxide


Input: We demonstrated the fabrication of inverted CdSe/CdS/ZnS quantum dot light emitting devices (QD-LEDs) using titanium dioxide (TiO2) as an electron-injection layer and investigated the operating mechanism by utilizing different hole-transport materials, 4, 4-N, N-dicarbazole-biphenyl (CBP) and 4, 4', 4''-tris (carbazol-9-yl)-triphenylamine (TCTA).

CdSe

CdS

ZnS

titanium dioxide

4, 4-N, N-dicarbazole-biphenyl

CBP

4, 4', 4''-tris (carbazol-9-yl)-triphenylamine

TCTA


Input: A more efficient device with CBP as the hole-transport layer (HTL) was obtained compared with the TCTA based device.

TCTA


Input: The peak efficiency of 6. 70 cd A (-1) for the CBP based device was found to be about 74. 5% higher than the TCTA based device (3. 84 cd A (-1)).

TCTA


Input: The studies on the time-resolved photoluminescence spectra of the QD-HTL composite structures showed that the energy transfer (ET) efficiencies from the two HTLs to the QD layer were similar and the charge separation between QDs and HTLs could be neglected.


Input: The enhancement in the performance of the CBP based device was attributed to the more efficient hole-injection from CBP to QDs.


Input: Nitrogen doped holey graphene as an efficient metal-free multifunctional electrochemical catalyst for hydrazine oxidation and oxygen reduction.

Nitrogen

graphene

hydrazine

oxygen


Input: Electrocatalysts for anode or cathode reactions are at the heart of electrochemical energy conversion and storage devices.


Input: Molecular design of carbon based nanomaterials may create the next generation electrochemical catalysts for broad applications.

carbon


Input: Herein, we present the synthesis of a three-dimensional (3D) nanostructure with a large surface area (784 m (2) g (-1)) composed of nitrogen doped (up to 8. 6 at.%) holey graphene.

nitrogen

graphene


Input: The holey structure of graphene sheets (~ 25% of surface area is attributed to pores) engenders more exposed catalytic active edge sites.

graphene


Input: Nitrogen doping further improves catalytic activity, while the formation of the 3D porous nanostructure significantly reduces graphene nanosheet stacking and facilitates the diffusion of reactants/electrolytes.

Nitrogen

graphene


Input: The three factors work together, leading to superb electrochemical catalytic activities for both hydrazine oxidation (its current generation ability is comparable to that of 10 wt% Pt-C catalyst) and oxygen reduction (its limiting current is comparable to that of 20 wt% Pt-C catalyst) with four-electron transfer processes and excellent durability.

hydrazine

Pt

C

oxygen

Pt

C


Input: Synthesis, in vitro antitumor evaluation and DNA-binding study of novel tetrahydroquinolines and some derived tricyclic and tetracyclic ring systems.

tetrahydroquinolines


Input: The synthesis of some new tetrahydroquinolines, tetrahydropyrimido [4, 5-b] quinolines, and tetrahydropentaazacyclopenta [a] anthracenes structurally related to some DNA intercalators is described.

tetrahydroquinolines

tetrahydropyrimido [4, 5-b] quinolines

tetrahydropentaazacyclopenta [a] anthracenes


Input: Fifteen compounds were evaluated for their antitumor activity by the National Cancer Institute (NCI), in vitro disease oriented antitumor screening.


Input: The most active tricyclic pyrimido [4, 5-b] quinolines 3b, 6b, 7b and 8b were further subjected to DNA-binding investigation in an attempt to rationalize their activity.

tricyclic pyrimido [4, 5-b] quinolines


Input: Compound 8b proved to be the most active member in this study as evidenced from its remarkable growth inhibitory potential against some individual cell lines, and its broad spectrum of antitumor activity (GI50, TGI and LC50 values 46. 9, 85. 3 and 97. 4, respectively), together with a good DNA-binding affinity.


Input: Energetic contribution to hydration shells in one-dimensional aqueous electrolyte solution by anomalous hydrogen bonds.

hydrogen


Input: The hydration structure of NaCl aqueous solution was elucidated in carbon nanotubes (CNTs) on the basis of canonical ensemble Monte Carlo simulations.

NaCl

carbon


Input: Hydration shells were preferentially formed even in narrow CNTs to gain stabilization energy, whereas hydrogen bonding between water molecules in such CNTs was sacrificed.

hydrogen


Input: Nanoscale-confined aqueous electrolyte solutions therefore prioritize hydration shell formation between ions and water rather than hydrogen-bond formation between water molecules.

hydrogen


Input: Electrophysiological study for comparing the effect of biological activity between type A botulinum toxins in rat gastrocnemius muscle.


Input: Background: New cosmetic applications and products based on the effects of botulinum toxin (BTX) treatment have stimulated demand for this class of natural compounds.


Input: This demand generates the need for appropriate standardized protocols to test and compare the effectiveness of new BTX preparations. Objectives: Based on the previously described electrophysiological methods, we measured and compared the inhibitory effects of two BTX type A (BTX-A) preparations on neuromuscular transmission through split-body test. Methods: The effectiveness was evaluated in terms of the compound muscle action potential (CMAP) and conduction velocity after BTX-A injection.


Input: We used a split-body method to compare two different BTX-As in the rat. Results: Based on the changes in the CMAP, the two different BTX-As induced paralytic effect on the rat tibialis anterior muscle.


Input: However, the two different BTX-A preparations did not differ significantly in effectiveness and did not induce a delay in conduction velocity. Conclusions: The new BTX-A preparation used in this electrophysiological study had similar effect compared with the previously marketed BTX-A. [AQ: Please approve the edits made to the sentence " The new BTX-A preparation ... ") We propose that a split-body electrophysiological protocol will be useful in establishing the comparative effectiveness of new BTX products.


Input: Generation and characterization of fully human monoclonal antibodies against human orai1 for autoimmune disease.


Input: Calcium entry into T cells following antigen stimulation is crucial for nuclear factor of activated T cells (NFAT)-mediated T cell activation.

Calcium


Input: The movement of calcium is mediated by calcium release-activated calcium (CRAC) channels.

calcium

calcium

calcium


Input: There are two key components of this channel: Orai1 is the pore-forming subunit located in the plasma membrane, and stromal interaction molecule 1 (STIM1) functions as a Ca (2 +) sensor in the endoplasmic reticulum.

Ca (2 +)


Input: A subset of human patients carry mutations in either STIM1 or Orai1 that affect protein function or expression, resulting in defective store-operated Ca (2 +) influx and CRAC channel function, and impaired T cell activation.

Ca (2 +)


Input: These patients suffer from a hereditary form of severe combined immune deficiency syndrome, highlighting the importance of the CRAC channel for T lymphocyte function in humans.


Input: Since autoreactive T cells play an important role in the development of autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, and organ transplantation, Orai1 becomes an attractive therapeutic target for ameliorating autoimmune disease.


Input: We developed a novel approach to inhibiting CRAC function by generating high-affinity fully human monoclonal antibodies to human Orai1.


Input: These antibodies inhibited ICRAC current, store-operated Ca (2 +) influx, NFAT transcription, and cytokine release.

Ca (2 +)


Input: These fully human antibodies to human Orai1 may represent a novel therapeutic approach for the treatment of autoimmunity.


Input: Binding Preference of Carbon Nanotube Over Proline-Rich Motif Ligand on SH3-Domain: A Comparison with Different Force Fields.

Carbon

Proline


Input: With the widespread applications of nanomaterials such as carbon nanotubes, there is a growing concern on the biosafety of these engineered nanoparticles, in particular their interactions with proteins.

carbon


Input: In molecular simulations of nanoparticle-protein interactions, the choice of empirical parameters (force fields) plays a decisive role, and thus is of great importance and should be examined carefully before wider applications.


Input: Here we compare three commonly used force fields, CHARMM, OPLSAA, and AMBER in study of the competitive binding of a single wall carbon nanotube (SWCNT) with a native proline-rich motif (PRM) ligand on its target protein SH3 domain, a ubiquitous protein-protein interaction mediator involved in signaling and regulatory pathways.

proline


Input: We find that the SWCNT displays a general preference over the PRM in binding with SH3 domain in all the three force fields examined, although the degree of preference can be somewhat different, with the AMBER force field showing the highest preference.


Input: The SWCNT prevents the ligand from reaching its native binding pocket by (i) occupying the binding pocket directly, and (ii) binding with the ligand itself and then being trapped together onto some off-sites.


Input: The pi-pi stacking interactions between the SWCNT and aromatic residues are found to play a significant role in its binding to the SH3 domain in all the three force fields.


Input: Further analyses show that even the SWCNT-ligand binding can also be relatively more stable than the native ligand-protein binding, indicating a serious potential disruption to the protein SH3 function.


Input: Follicular Variant of Papillary Thyroid Carcinoma is a Unique Clinical Entity: A Population-Based Study of 10, 740 Cases.


Input: Background: Follicular variant of papillary thyroid carcinoma (FV-PTC) has been increasingly diagnosed in recent years.


Input: However, little is known about its clinical behavior.


Input: The purpose of this study was to determine the disease characteristics of FV-PTC, and to compare it with classical papillary thyroid carcinoma (C-PTC) and follicular thyroid carcinoma (FTC).


Input: Methods: All cases of C-PTC, FV-PTC and FTC larger than 1 cm in the Surveillance, Epidemiology and End Results (SEER) Cancer Database from 1988 to 2007 were identified.


Input: Tumor behavior and patient survival were compared among these three groups.


Input: Different risk factors for disease-specific mortality in each group were evaluated by multivariate analysis.


Input: Results: A total over 36, 000 surgical cases were identified including 21, 796 C-PTCs, 10, 740 FV-PTCs and 3, 958 FTCs.


Input: Extrathyroidal extension and lymph node metastases were more common in FV-PTC than in FTC, but significantly less common than in C-PTC (p < 0. 0001).


Input: Distant metastasis rate were present in 2% of patients with FV-PTC, 1% in C-PTC and 4% in FTC (p < 0. 0001).


Input: The 10-year disease-specific survival for patients with FV-PTC was 98%, similar to C-PTC (97%), but better than FTC (94%, p < 0. 0001).


Input: Age greater than 45 years remained a strong risk factor for disease-specific mortality in both FV-PTC and C-PTC, while the presence of extrathyroidal extension and distant metastases were stronger predictors of disease-specific mortality in FV-PTC than in C-PTC.


Input: Conclusions: FV-PTC is a common variant of PTC.


Input: Its clinical behavior is unique and represents an intermediate entity with clinical features that are between C-PTC and FTC.


Input: Interestingly, despite the variations in clinical behavior, the long-term outcome of these patients remains excellent and similar to C-PTC.


Input: Design, Synthesis, and Pharmacological Characterization of Novel Endomorphin-1 Analogues as Extremely Potent mu-Opioid Agonists.


Input: Recently we reported the synthesis and structure-activity study of endomorphin-1 (EM-1) analogues containing novel, unnatural alpha-methylene-beta-aminopropanoic acids (Map).

alpha-methylene-beta-aminopropanoic acids

Map


Input: In the present study, we describe new EM-1 analogues containing Dmt (1), (R/S)-beta Pro (2), and (ph) Map (4)/(2-furyl) Map (4).

Dmt

(R/S)-beta Pro

(ph) Map

(2-furyl) Map


Input: All of the analogues showed a high affinity for the mu-opioid receptor (MOR) and increased stability in mouse brain homogenates.


Input: Of the new compounds, Dmt (1)-(R)-beta Pro (2)-Trp (3)-(2-furyl) Map (4) (analogue 12) displayed the highest affinity toward MOR, in the picomolar range (Ki (mu) = 3. 72 pM).

Dmt

(R)-beta Pro

Trp

(2-furyl) Map


Input: Forskolin-induced cAMP accumulation assays indicated that this analogue displayed an extremely high agonistic potency, in the subpicomolar range (EC50 = 0. 0421 pM, Emax = 99. 5%).

Forskolin

cAMP


Input: This compound also displayed stronger in vivo antinociceptive activity after iv administration when compared to morphine in the tail-flick test, which indicates that this analogue was able to cross the blood-brain barrier.

morphine


Input: Isocoumarin Derivatives and Benzofurans from a Sponge-Derived Penicillium sp.

Isocoumarin

Benzofurans


Input: Fungus.


Input: Ten new fungal metabolites, including three hydroisocoumarins, penicimarins A-C (1-3), three isocoumarins, penicimarins D-F (6-8), and four benzofurans, penicifurans A-D (11-14), together with four known isocoumarin derivatives (4, 5, 9, 10), were obtained from the sponge-derived fungus Penicillium sp.

hydroisocoumarins

penicimarins A-C

isocoumarins

penicimarins D-F

benzofurans

penicifurans A-D

isocoumarin


Input: MWZ14-4, collected from the South China Sea.


Input: Their planar structures and relative configurations were elucidated by detailed analysis of spectroscopic data and by comparison with related known compounds.


Input: The absolute configurations of 1-4 were assigned by the modified Mosher' s method and TDDFT ECD calculations together with comparison of their CD spectra.


Input: Compound 1 represents a rare naturally occurring isocoumarin derivative with 4-substitution, but no substituent at the 3-position.

isocoumarin


Input: These compounds were evaluated for antibacterial activities and cytotoxic activities in vitro.


Input: Among them, penicifuran A (11) exhibited inhibitory activity against Staphylococcus albus with an MIC value of 3. 13 mu M.

penicifuran A


Input: Comparison of the inhibitory effect against copper ion-induced oxidation in rat plasma after oral administration of salvianolic acid B and its decocted solutions.

copper

salvianolic acid B


Input: The effects of salvianolic acid B (Sal B) decoction on antioxidative activities were evaluated.

salvianolic acid B

Sal B


Input: The 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity, Fe (2 +)-chelating activity, reducing power, and total phenolic content of the Sal B-decocted solutions did not change significantly after decoction in an aqueous solution.

2, 2-diphenyl-1-picrylhydrazyl

DPPH

Fe (2 +)

phenolic

Sal B


Input: However, the formation of cholesteryl ester hydroperoxide (CE-OOH) in rat blood plasma containing the Sal B-decocted solutions was more effectively inhibited than that of plasma containing the Sal B solution, regardless of the decoction time.

cholesteryl ester hydroperoxide

CE-OOH

Sal B

Sal B


Input: In addition, the accumulation of CE-OOH in rat plasma after oral administration of the Sal B-decocted solutions was more effectively suppressed than when the Sal B solution was administered, considering the lag time.

CE-OOH

Sal B

Sal B


Input: It is likely that the decoction was partly responsible for the increased antioxidant activity in blood plasma.


Input: Therefore, the Sal B-decocted solution may contribute more to antioxidant defense in blood than a Sal B solution that is not decocted.

Sal B

Sal B


Input: Cucurbitacin I inhibits rac1 activation in breast cancer cells by a reactive oxygen species-mediated mechanism and independently of janus tyrosine kinase 2 and p-rex1.

Cucurbitacin I

oxygen

tyrosine


Input: The small GTPase Rac1 has been widely implicated in mammary tumorigenesis and metastasis.


Input: Previous studies established that stimulation of ErbB receptors in breast cancer cells activates Rac1 and enhances motility via the Rac-guanine nucleotide exchange factor P-Rex1.

guanine nucleotide


Input: As the Janus tyrosine kinase 2 (Jak2)/signal transducer and activator of transcription 3 (Stat3) pathway has been shown to be functionally associated with ErbB receptors, we asked if this pathway could mediate P-Rex1/Rac1 activation in response to ErbB ligands.

tyrosine


Input: Here we found that the anticancer agent cucurbitacin I, a Jak2 inhibitor, reduced the activation of Rac1 and motility in response to the ErbB3 ligand heregulin in breast cancer cells.

cucurbitacin I


Input: However, Rac1 activation was not affected by Jak2 or Stat3 RNA interference, suggesting that the effect of cucurbitacin I occurs through a Jak2-independent mechanism.

cucurbitacin I


Input: Cucurbitacin I also failed to affect the activation of P-Rex1 by heregulin.

Cucurbitacin I


Input: Subsequent analysis revealed that cucurbitacin I strongly activates RhoA and the Rho effector Rho kinase (ROCK) in breast cancer cells and induces the formation of stress fibers.

cucurbitacin I


Input: Interestingly, disruption of the RhoA-ROCK pathway prevented the inhibitory effect of cucurbitacin I on Rac1 activation by heregulin.

cucurbitacin I


Input: Lastly, we found that RhoA activation by cucurbitacin I is mediated by reactive oxygen species (ROS).

cucurbitacin I

oxygen


Input: The ROS scavenger N-acetyl l-cysteine and the mitochondrial antioxidant Mito-TEMPO rescued the inhibitory effect of cucurbitacin I on Rac1 activation.

N-acetyl l-cysteine

cucurbitacin I


Input: In conclusion, these results indicate that ErbB-driven Rac1 activation in breast cancer cells proceeds independently of the Jak2 pathway.


Input: Moreover, they established that the inhibitory effect of cucurbitacin I on Rac1 activity involves the alteration of the balance between Rho and Rac.

cucurbitacin I


Input: Synthesis and in-silico studies of some diaryltriazole derivatives as potential cyclooxygenase inhibitors.

diaryltriazole


Input: The synthesis of several 4-phenyl-5-pyridin-4-yl-2, 3-dihydro-3H-1, 2, 4-triazole-3-thiones possessing N-2 Mannich bases or S-alkyl substituents, is reported.

4-phenyl-5-pyridin-4-yl-2, 3-dihydro-3H-1, 2, 4-triazole-3-thiones

Mannich bases

S-alkyl


Input: Several of them exhibited a low nanomolar COX enzyme inhibition activity.


Input: Most of the compounds showed inhibition of edema was similar to that evoked by celocoxib in animal model.

celocoxib


Input: Molecular docking studies of the compounds into the binding sites of COX-1 and COX-2 allowed us to shed light on the binding mode of these novel COX inhibitors.


Input: Antibacterial substances from Albizia myriophylla wood against cariogenic Streptococcus mutans.


Input: Albizia myriophylla has been used for long by Thai traditional healers as an important ingredient herb in Thai herbal formulas for caries.


Input: In this study, three flavonoids lupinifolin (6), 8-methoxy-7, 3', 4'-trihydroxyflavone (7), and 7, 8, 3', 4'-tetrahydroxyflavone (8), a triterpenoid lupeol (3) as well as four sterols beta-sitosterone (1), stigmasta-5, 22-dien-3-one (2), beta-sitosterol (4), and stigmasterol (5) were isolated from A. myriophylla wood.

lupinifolin

8-methoxy-7, 3', 4'-trihydroxyflavone

7, 8, 3', 4'-tetrahydroxyflavone

triterpenoid lupeol

sterols beta-sitosterone

stigmasta-5, 22-dien-3-one

beta-sitosterol

stigmasterol


Input: The antibacterial activity of these compounds against Streptococcus mutans ATCC 25175 was performed using broth microdilution method.


Input: All compounds exhibited antibacterial activity against S. mutans with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) ranging from 1-256 and 2-256 mu g/ml, respectively.


Input: Among the isolated compounds, lupinifolin (6) was found to be the most potent with MIC and MBC of 1 and 2 mu g/ml, respectively.

lupinifolin


Input: Lupinifolin (6) also showed a strong activity against ten clinical isolates of S. mutans with MIC and MBC ranging from 0. 25-2 and 0. 5-8 mu g/ml, respectively.

Lupinifolin


Input: These results reported the bioactive ingredients of A. myriophylla which support its ethnomedical claims as well.


Input: Lupinifolin (6) may have a potential to be a natural anticariogenic agent.

Lupinifolin


Input: Association of cadmium and lead with antioxidant status and incidence of benign prostatic hyperplasia in patients of Western India.

cadmium


Input: The association of cadmium (Cd) and lead (Pb) in the pathophysiology and progression of benign prostate hyperplasia (BPH) has been evaluated in an epidemiological study with 116 BPH patients of the western part of India.

cadmium

Cd

Pb


Input: The prostatic acid phosphatase activity, prostate-specific antigen, maximum urinary flow rate (Q max), and redox status of BPH patients were correlated with Cd and Pb contents.

Cd

Pb


Input: Additionally, patients were also separated on the basis of their age, genetic lineage, and additive habits and correlated with the Cd, Pb, and Q max levels.

Cd

Pb


Input: Our results suggest that the accumulation of toxic metals in prostate tissue has a significant positive correlation with the pathogenesis of BPH.


Input: Cd and Pb exert their effects through altered antioxidant defense mechanisms, ultimately leading to increased BPH severity.

Cd

Pb


Input: Progression of the pathogenesis also depends on other factors such as additive habits, genetic lineage, and age of the patients.


Input: [6]-gingerol: a novel AT 1 antagonist for the treatment of cardiovascular disease.


Input: Considering the prevalence of cardiovascular disease in public health and the limited validated therapeutic options, this study aimed to find novel compounds targeting the angiotensin II type 1 receptor, accepted as a therapeutic target in cardiovascular disease.


Input: A small library consisting of 89 compounds from 39 Chinese herbs was profiled using a cell-based calcium mobilization assay which was developed and characterized for high-throughput screening.


Input: [6]-Gingerol derived from Zingiber officinale Roscoe (ginger) was identified as a novel angiotensin II type 1 receptor antagonist, with an IC50 value of 8. 173 micro M.


Input: The hit was further tested by a specificity assay indicating that it had no antagonistic effects on other evaluated GPCRs, such as endothelin receptors.


Input: The major ingredient of ginger, [6]-gingerol, could inhibit angiotensin II type 1 receptor activation, which partially clarified the mechanism of ginger regulating blood pressure and strengthening heart in the cardiovascular system.


Input: Peltogynoids and 2-Phenoxychromones from Peltophorum pterocarpum and Evaluation of Their Estrogenic Activity.

Peltogynoids


Input: Phytochemical investigation of the dichloromethane extract of the leaves of Peltophorum pterocarpum, a tropical ornamental tree, led to the isolation of twelve compounds (1-12).

dichloromethane


Input: One new derivative of peltogynoid ophioglonin (1) and a new 2-phenoxychromone (2) with its 3'-O-beta-D-glucoside derivative (3) are described here for the first time.

ophioglonin


Input: In addition, nine flavonoid derivatives, including peltogynoid ophioglonin (4), were isolated for the first time from this plant.

ophioglonin


Input: The structures were determined by spectroscopic and chemical methods.


Input: Evaluation of the estrogenic activities of 1, 2, and 4 using different model cell systems revealed that 4 was estrogenic and that 2 was largely inactive.


Input: Interestingly, 1 was unable to stimulate the proliferation of breast and endometrial cancer cells but exhibited substantial estrogen receptor alpha-mediated activation of gene expression.

estrogen


Input: This observation indicates that 1 can be further evaluated for its cancer chemopreventive potential.


Input: First-Line Management of EGFR-Mutated Advanced Lung Adenocarcinoma: Recent Developments.


Input: Gefitinib and erlotinib are small-molecule reversible tyrosine kinase inhibitors (TKIs) of epidermal growth factor receptor (EGFR).

Gefitinib

erlotinib

tyrosine


Input: Objective responses have been observed frequently in patients with non-small cell lung cancer (NSCLC) harbouring activating EGFR mutations, the most common being deletions in exon 19 and the exon 21 L858R mutation.


Input: EGFR mutations are prevalent in female patients, those who have never smoked, those of Asian ethnicity and those who have adenocarcinoma histology.


Input: Given the efficacy of EGFR TKIs in advanced NSCLC in the salvage setting, and their favourable toxicity profile compared with conventional chemotherapy, there is considerable interest in evaluating their efficacy in the first-line treatment of advanced NSCLC.


Input: To date, there have been several phase II and phase III studies that have examined the efficacy of first-line single-agent EGFR TKIs in unselected, clinically selected or molecularly selected populations.


Input: Here we review and compare the differences in these phase III trials.


Input: Most phase III trials chose progression-free survival (PFS) rather than overall survival (OS) as their primary endpoint.


Input: PFS was prolonged but OS was not.


Input: The recent development of novel irreversible EGFR TKIs, such as afatinib and dacomitinib, is also reviewed.

afatinib

dacomitinib


Input: The 5-hydroxytryptamine (serotonin) receptor 6 agonist EMD 386088 ameliorates ketamine-induced deficits in attentional set shifting and novel object recognition, but not in the prepulse inhibition in rats.

serotonin

EMD 386088

ketamine


Input: Preclinical data suggest that the 5-hydroxytryptamine (serotonin) 6 (5-HT6) receptor may be a potential target for the development of new therapies for treating cognitive dysfunctions in schizophrenia and other central nervous system disorders.

serotonin


Input: Recent evidence indicates that not only blockade but also activation of 5-HT6 receptors exerts procognitive effects.


Input: Nevertheless, little is known about the potential efficacy of 5-HT6 receptor agonists in models of schizophrenia-like cognitive deficits.


Input: The aim of the present study was to evaluate the effects of the 5-HT6 receptor agonist, EMD 386088, on the ketamine-induced deficits in the attentional set-shifting task (ASST), novel object recognition (NOR) task and prepulse inhibition (PPI) task in rats.

EMD 386088

ketamine


Input: Acute administration of EMD 386088 (2. 5 and 5 mg/kg, intraperitoneally) to Sprague-Dawley rats reversed the deficit in the ASST induced by repeated ketamine administration.

EMD 386088

ketamine


Input: Moreover, the ketamine-induced deficit in the NOR task was ameliorated by EMD 386088 at a dose of 5 mg/kg.

ketamine

EMD 386088


Input: However, in contrast to the antipsychotic drug clozapine, the 5-HT6 agonist did not affect PPI disrupted by ketamine.

clozapine

ketamine


Input: The present study demonstrated the beneficial effects of the 5-HT6 agonist in ameliorating some of the ketamine-induced deficits relevant to schizophrenia.

ketamine


Input: It thus seems likely that the 5-HT6 receptor activation may represent a useful pharmacological approach to the treatment of cognitive disturbances observed in this disorder.


Input: Multilevel regulation of 2-cys peroxiredoxin reaction cycle by s-nitrosylation.

cys


Input: S-Nitrosothiols (SNOs), formed by nitric oxide (NO)-mediated S-nitrosylation, and hydrogen peroxide (H2O2), a prominent reactive oxygen species, are implicated in diverse physiological and pathological processes.

S-Nitrosothiols

SNOs

nitric oxide

NO

S

hydrogen peroxide

oxygen


Input: Recent research has shown that the cellular action and metabolism of SNOs and H2O2 involve overlapping, thiol-based mechanisms, but how these reactive species may affect each other' s fate and function is not well understood.

SNOs

thiol


Input: In this study we investigated how NO/SNO may affect the redox cycle of mammalian peroxiredoxin-1 (Prx1), a representative of the 2-Cys Prxs, a group of thioredoxin (Trx)-dependent peroxidases.

NO

SNO

Cys


Input: We found that, both in a cell-free system and in cells, NO/SNO donors such as S-nitrosocysteine and S-nitrosoglutathione readily induced the S-nitrosylation of Prx1, causing structural and functional alterations.

NO

SNO

S-nitrosocysteine

S-nitrosoglutathione

S


Input: In particular, nitrosylation promoted disulfide formation involving the pair of catalytic cysteines (Cys-52 and Cys-173) and disrupted the oligomeric structure of Prx1, leading to loss of peroxidase activity.

disulfide

cysteines

Cys

Cys


Input: A highly potent inhibition of the peroxidase catalytic reaction by NO/SNO was seen in assays employing the coupled Prx-Trx system.

NO

SNO


Input: In this setting, S-nitrosocysteine (10 mu m) effectively blocked the Trx-mediated regeneration of oxidized Prx1.

S-nitrosocysteine


Input: This effect appeared to be due to both competition between S-nitrosocysteine and Prx1 for the Trx system and direct modulation by S-nitrosocysteine of Trx reductase activity.

S-nitrosocysteine

S-nitrosocysteine


Input: Our findings that NO/SNO target both Prx and Trx reductase may have implications for understanding the impact of nitrosylation on cellular redox homeostasis.

NO

SNO


Input: Purification and sidewall functionalization of multiwalled carbon nanotubes and resulting bioactivity in two macrophage models.

carbon


Input: This study examined the consequences of surface carboxylation of multiwalled carbon nanotubes (MWCNT) on bioactivity.

carbon


Input: Since commercial raw MWCNT contain impurities that may affect their bioactivity, HCl refluxing was exploited to purify raw " as-received " MWCNT by removing the amorphous carbon layer on the MWCNT surface and reducing the metal impurities (e. g. Ni).

HCl

carbon

Ni


Input: The removal of amorphous carbon layer was confirmed by Raman spectroscopy and thermogravimetric analysis.

carbon


Input: Furthermore, the HCl-purified MWCNT provided more available reaction sites, leading to enhanced sidewall functionalization.

HCl


Input: The sidewall of HCl-purified MWCNT was further functionalized with the-COOH moiety by HNO (3) oxidation.

HCl

COOH

HNO (3)


Input: This process resulted in four distinct MWCNT: raw, purified,-COOH-terminated raw MWCNT, and-COOH-terminated purified MWCNT.

COOH

COOH


Input: Freshly isolated alveolar macrophages from C57Bl/6 mice were exposed to these nanomaterials to determine the effects of the surface chemistry on the bioactivity in terms of cell viability and inflammasome activation.


Input: Inflammasome activation was confirmed using inhibitors of cathepsin B and Caspase-1.


Input: Purification reduced the cell toxicity and inflammasome activation slightly compared to raw MWCNT.


Input: In contrast, functionalization of MWCNT with the-COOH group dramatically reduced the cytotoxicity and inflammasome activation.

COOH


Input: Similar results were seen using THP-1 cells supporting their potential use for high-throughput screening.


Input: This study demonstrated that the toxicity and bioactivity of MWCNT were diminished by removal of the Ni contamination and/or addition of-COOH groups to the sidewalls.

Ni

COOH


Input: Experimental and computational study of the interaction of novel colchicinoids with a recombinant human alpha I/beta I-tubulin heterodimer.

colchicinoids


Input: The binding free energies on human tubulin of selected colchicine and thiocolchicine compounds were determined.

colchicine

thiocolchicine


Input: Two methods were used for the determination of binding free energies.


Input: One is based on theoretical prediction simulating the dissociation of the compound from tubulin using a series of molecular dynamics simulations.


Input: The other method involved a series of experiments that measured the affinity of the compound on a synthetically expressed and purified tubulin protein using a spectrofluorometric technique.


Input: (c) 2013 John Wiley & Sons A/S.


Input: Polyallylamine functionalized palladium icosahedra: one-pot water-based synthesis and their superior electrocatalytic activity and ethanol tolerant ability in alkaline media.

Polyallylamine

palladium icosahedra

ethanol


Input: Polyallylamine (PAH) functionalized Pd icosahedra are synthesized through a simple, one-pot, seedless and hydrothermal growth method.

Polyallylamine

PAH

Pd icosahedra


Input: Herein, PAH is used efficiently as a complex-forming agent, capping agent, and facet-selective agent.

PAH


Input: The strong interaction between PAH and Pd atom sharply changes the electronic structure of Pd atom in the Pd icosahedra.

PAH

Pd

Pd

Pd icosahedra


Input: The protective function of PAH layers and enhanced antietching capability of Pd atom are responsible for the formation of the Pd icosahedra.

PAH

Pd

Pd icosahedra


Input: Very importantly, the as-prepared PAH functionalized Pd icosahedra exhibit superior electrocatalytic activity and ethanol tolerant ability toward the oxygen reduction reaction (ORR) compared to the commercially available Pt black in alkaline media.

PAH

Pd icosahedra

ethanol

oxygen

Pt black


Input: At 0. 95 V (vs RHE), the ORR specific kinetic current density at the Pd icosahedra is 4. 48 times higher than that at commercial Pt black.

Pd icosahedra

Pt black


Input: The fact demonstrates the appropriate surface modification of the Pd nanoparticles by nonmetallic molecules can be regarded as an effective way to enhance the electrocatalytic activity toward the ORR.

Pd


Input: Self-Assembling Multidomain Peptide Fibers with Aromatic Cores.


Input: Self-assembling multidomain peptides have been shown to have desirable properties, such as the ability to form hydrogels that rapidly recover following shear-thinning and the potential to be tailored by amino acid selection to vary their elasticity and encapsulate and deliver proteins and cells.

amino acid


Input: Here we describe the effects of substitution of aliphatic hydrophobic amino acids in the central domain of the peptide for the aromatic amino acids phenylalanine, tyrosine, and tryptophan.

amino acids

aromatic amino acids phenylalanine

tyrosine

tryptophan


Input: While the basic nanofibrous morphology is retained in all cases, selection of the particular core residues results in switching from antiparallel hydrogen bonding to parallel hydrogen bonding in addition to changes in nanofiber morphology and in hydrogel rheological properties.

hydrogen

hydrogen


Input: Peptide nanofiber assemblies are investigated by circular dichroism polarimetry, infrared spectroscopy, atomic force microscopy, transmission and scanning electron microscopy, oscillatory rheology, and molecular dynamics simulations.


Input: Results from this study will aid in designing next generation cell scaffolding materials.


Input: Production and characterization of pellets using Avicel CL611 as spheronization aid.


Input: Abstract Purpose: The study looked into the feasibility of producing pellet using Avicel CL611 as spheronization aid by the extrusion/spheronization technique.


Input: Methods: Pellets were formulated to contain either 20% or 40% Avicel CL611 and lactose monohydrate as the other sole ingredient.

lactose monohydrate


Input: Water is used as liquid binder.


Input: Quality of pellets and extrudates were analyzed for size distribution, shape, surface tensile strength and disintegration profile.


Input: Results: More water was needed when higher Avicel CL611 fraction was used during the production of pellets.


Input: The pellets of larger size were obtained by increasing the water content.


Input: Pellets with aspect ratios of ~ 1. 1 were produced with high spheronization speed at short residence time.


Input: Higher tensile strength was achieved when increasing the water content and the fraction of Avicel CL611 during pellet production.


Input: These pellets also took longer time to disintegrate, nonetheless all the pellets disintegrated within 15 min.


Input: A positive linear relationship was obtained between the tensile strength and time for pellets to disintegrate.


Input: Conclusion: Strong but round pellets that disintegrate rapidly could be produced with Avicel CL611 as spheronization aid using moderately soluble compounds such as lactose.

lactose


Input: A Novel CUG (exp). MBNL1 Inhibitor with Therapeutic Potential for Myotonic Dystrophy Type 1.


Input: Myotonic dystrophy type 1 (DM1) is caused by an expanded CUG repeat (CUG (exp)) that sequesters muscleblind-like 1 protein (MBNL1), a protein that regulates alternative splicing.


Input: CUG (exp) RNA is a validated drug target for this currently untreatable disease.


Input: Herein, we develop a bioactive small molecule (1) that targets CUG (exp) RNA and is able to inhibit the CUG (exp). MBNL1 interaction in cells that model DM1.


Input: The core of this small molecule is based on ligand 2, which was previously reported to be active in an in vitro assay.


Input: A polyamine-derivative side chain was conjugated to this core to make it aqueous-soluble and cell-penetrable.

polyamine


Input: In a DM1 cell model this conjugate was found to disperse CUG (exp) ribonuclear foci, release MBNL1, and partially reverse the mis-splicing of the insulin receptor pre-mRNA.


Input: Direct evidence for ribonuclear foci dispersion by this ligand was obtained in a live DM1 cell model using time-lapse confocal microscopy.


Input: Predicting ligand binding modes from neural networks trained on protein-ligand interaction fingerprints.


Input: We herewith present a novel approach to predict protein-ligand binding modes from the single two-dimensional structure of the ligand.


Input: Known protein-ligand X-ray structures were converted into binary bit strings encoding protein-ligand interactions.


Input: An artificial neural network was then set up to first learn and then predict protein-ligand interaction fingerprints from simple ligand descriptors.


Input: Specific models were constructed for three targets (CDK2, p38-alpha, HSP90-alpha) and 146 ligands for which protein-ligand X-ray structures are available.


Input: These models were able to predict protein-ligand interaction fingerprints and to discriminate important features from minor interactions.


Input: Predicted interaction fingerprints were successfully used as descriptors to discriminate true ligands from decoys by virtual screening.


Input: In some but not all cases, the predicted interaction fingerprints furthermore enable to efficiently rerank cross-docking poses and prioritize the best possible docking solutions.


Input: Are the intramolecular o-h... f and o-h... cl hydrogen bonds maintained in solution?

o-h

f

o-h

cl hydrogen


Input: A theoretical study.


Input: The present case study aims at calculating the equilibrium conformer compositions for 2X-ethanol and 2X-phenol (X = F, Cl) in solution, and exploring the effect of the applied theoretical method and basis set on the obtained results, as well as considering the usefulness of the continuum solvent approach in comparison with the explicit solvent Monte Carlo model utilizing the free energy perturbation method.

ethanol

phenol

F

Cl


Input: Gas-phase optimizations at the DFT/B97D/aug-cc-pvtz and ab initio MP2/aug-cc-pvtz levels predicted structures in good agreement with the available experimental data for three test molecules.


Input: Because in-solution geometries change only slightly according to the IEF-PCM continuum solvent calculations in carbon tetrachloride and water, the two theoretical levels were applied further on, and complete basis set (CBS) relative internal free energies were estimated for the conformers under study.

carbon tetrachloride


Input: The predicted OCCF gauche/trans ratio for 2F-ethanol was well reproduced in comparison with available experimental compositions.

OCCF


Input: The predominant gauche structure maintains an intramolecular hydrogen bond in carbon tetrachloride (HB structure), whereas HB and NoHB gauche conformers appear in nearly the same fraction in aqueous solution.

hydrogen

carbon tetrachloride


Input: The internally hydrogen-bonded conformer is predominant also for 2X-phenol species, as calculated on the basis of relative CBS internal free energies and IEF-PCM and FEP/MC solvation free energies.

hydrogen

phenol


Input: Use of a trihydrate supermolecule model for 2F-ethanol conformers leads to the prediction of the aqueous-solution composition in contrast to the experiment.

trihydrate


Input: Solution structure modeling predicts weak hydrogen-bond formation capacity for both the covalently bound F and Cl atoms, even in conformations where they are fully exposed to hydration.

hydrogen

F

Cl


Input: Effect of Solvent Polarity on the Vibrational Dephasing Dynamics of the Nitrosyl Stretch in an Fe (II) Complex Revealed by 2D IR Spectroscopy.

Nitrosyl

Fe (II)


Input: The vibrational dephasing dynamics of the nitrosyl stretching vibration (nu NO) in sodium nitroprusside (SNP, Na2 [Fe (CN) 5NO]. 2H2O) are investigated using two-dimensional infrared (2D IR) spectroscopy.

nitrosyl

NO

sodium nitroprusside

SNP

Na2 [Fe (CN) 5NO]. 2H2O


Input: The nu NO in SNP acts as a model system for the nitrosyl ligand found in metalloproteins which play an important role in the transportation and detection of nitric oxide (NO) in biological systems.

NO

SNP

nitrosyl

nitric oxide

NO


Input: We perform a 2D IR line shape study of the nu NO in the following solvents: water, deuterium oxide, methanol, ethanol, ethylene glycol, formamide, and dimethyl sulfoxide.

NO

deuterium oxide

methanol

ethanol

ethylene glycol

formamide

dimethyl sulfoxide


Input: The frequency of the nu NO exhibits a large vibrational solvatochromic shift of 52 cm (-1), ranging from 1884 cm (-1) in dimethyl sulfoxide to 1936 cm (-1) in water.

NO

dimethyl sulfoxide


Input: The vibrational anharmonicity of the nu NO varies from 21 to 28 cm (-1) in the solvents used in this study.

NO


Input: The frequency-frequency correlation functions (FFCFs) of the nu NO in SNP in each of the seven solvents are obtained by fitting the experimentally obtained 2D IR spectra using nonlinear response theory.

NO

SNP


Input: The fits to the 2D IR line shape reveal that the spectral diffusion time scale of the nu NO in SNP varies from 0. 8 to 4 ps and is negatively correlated with the empirical solvent polarity scales.

NO

SNP


Input: We compare our results with the experimentally determined FFCFs of other charged vibrational probes in polar solvents and in the active sites of heme proteins.

heme


Input: Our results suggest that the vibrational dephasing dynamics of the nu NO in SNP reflect the fluctuations of the nonhomogeneous electric field created by the polar solvents around the nitrosyl and cyanide ligands.

NO

SNP

nitrosyl

cyanide


Input: The solute solvent interactions occurring at the trans-CN ligand are sensed through the pi-back-bonding network along the Fe-NO bond in SNP.

trans-CN

Fe-NO

SNP


Input: Nicotinic acid conjugates of nonsteroidal anti-inflammatory drugs (NSAID' s) and their anti-inflammatory properties.

Nicotinic acid


Input: A series of nicotinic acid conjugates with non-steroidal anti-inflammatory drugs (NSAID' s) have been effectively synthesized using TBTU in high yield and purity.

nicotinic acid

TBTU


Input: All the synthesized conjugates were evaluated for their in vitro anti-inflammatory activity.


Input: Modulation of cellular insulin signaling and PTP1B effects by lipid metabolites in skeletal muscle cells.


Input: Normal glucose regulation is achieved by having adequate insulin secretion and effective glucose uptake/disposal.

glucose

glucose


Input: Excess lipids in peripheral tissues-skeletal muscle, liver and adipose tissue-may attenuate insulin signaling through the protein kinase B (AKt) pathway and up-regulate protein tyrosine phosphatase 1B (PTP1B), a negative regulator of insulin signaling.

tyrosine


Input: We studied accumulation of lipid metabolites [triglycerides (TAGs), diglycerides (DAGs)] and ceramides in relation to insulin signaling and expression and phosphorylation of PTP1B by preincubating rat skeletal muscle cells (L6 myotubes) with three saturated and three unsaturated free fatty acids (FFAs) (200 mu M).

triglycerides

TAGs

diglycerides

DAGs

ceramides

fatty acids


Input: Cells were also evaluated in the presence of wortmannin, an inhibitor of phosphatidylinositol 3-kinases and thus AKt (0-100 nM).

wortmannin

phosphatidylinositol


Input: Unsaturated FFAs increased DAGs, TAGs and PTP1B expression significantly, but cells remained insulin sensitive as assessed by robust AKt and PTP1B phosphorylation at serine (Ser) 50, Ser 398 and tyrosine 152.

DAGs

TAGs

serine

Ser

Ser

tyrosine


Input: Saturated palmitic and stearic acids increased ceramides, up-regulated PTP1B, and had AKt and PTP1B phosphorylation at Ser 50 impaired.

palmitic and stearic acids

ceramides

Ser


Input: We show a significant correlation between phosphorylation levels of AKt and of PTP1B at Ser 50 (R (2) = 0. 84, P <. 05).


Input: The same was observed with increasing wortmannin dose (R (2) = 0. 73, P <. 05).

wortmannin


Input: Only FFAs that increased ceramides caused impairment of AKt and PTP1B phosphorylation at Ser 50.

ceramides

Ser


Input: PTP1B overexpression in the presence of excess lipids may not directly cause insulin resistance unless it is accompanied by decreased PTP1B phosphorylation.


Input: A clear relationship between PTP1B phosphorylation levels at Ser 50 and its negative effect on insulin signaling is shown.

Ser


Input: Aphanamgrandiol A, a new triterpenoid with a unique carbon skeleton from Aphanamixis grandifolia.

Aphanamgrandiol A

triterpenoid

carbon


Input: Aphanamgrandiol A (1), a novel triterpenoid with a bicyclo [3, 2, 1] octane ring skeleton produced by 2, 3-ring opening and 2, 6-ring closure, was isolated from the stems of Aphanamixis grandifolia.

Aphanamgrandiol A

triterpenoid

bicyclo [3, 2, 1] octane


Input: The structures were established on the basis of extensive spectroscopic methods, including 1D and 2D NMR techniques, and determined unambiguously by X-ray crystal diffraction.


Input: Aphanamgrandiol A showed moderate cytotoxicities against MCG-803, SKOV-3, HCT116 and HepG2 cell lines.

Aphanamgrandiol A


Input: N-substituted azaindoles as potent inhibitors of Cdc7 kinase.

N-substituted azaindoles


Input: Cdc7 kinase is responsible for the initiation and regulation of DNA replication and has been proposed as a target for cancer therapy.


Input: We have identified a class of Cdc7 inhibitors based on a substituted indole core.

indole


Input: Synthesis of focused indole and azaindole analogs yielded potent and selective 5-azaindole Cdc7 inhibitors with improved intrinsic metabolic stability (ie 36).

indole

azaindole


Input: In parallel, quantum mechanical conformational analysis helped to rationalize SAR observations, led to a proposal of the preferred binding conformation in the absence of co-crystallography data, and allowed the design of 7-azaindole 37 as a second lead in this series.


Input: Helicusin E, Isochromophilone X and Isochromophilone XI: New Chloroazaphilones Produced by the Fungus Bartalinia robillardoides Strain LF550.

Helicusin E

Isochromophilone X

Isochromophilone XI

Chloroazaphilones


Input: Microbial studies of the Mediterranean sponge Tethya aurantium led to the isolation of the fungus Bartalinia robillardoides strain LF550.


Input: The strain produced a number of secondary metabolites belonging to the chloroazaphilones.

chloroazaphilones


Input: This is the first report on the isolation of chloroazaphilones of a fungal strain belonging to the genus Bartalinia.

chloroazaphilones


Input: Besides some known compounds (helicusin A (1) and deacetylsclerotiorin (2)), three new chloroazaphilones (helicusin E (3); isochromophilone X (4) and isochromophilone XI (5)) and one new pentaketide (bartanolide (6)) were isolated.

helicusin A

deacetylsclerotiorin

chloroazaphilones

helicusin E

isochromophilone X

isochromophilone XI

pentaketide

bartanolide


Input: The structure elucidations were based on spectroscopic analyses.


Input: All isolated compounds revealed different biological activity spectra against a test panel of four bacteria: three fungi; two tumor cell lines and two enzymes.


Input: Transcriptional responses indicate attenuated oxidative stress in the springtail Folsomia candida exposed to mixtures of cadmium and phenanthrene.

cadmium

phenanthrene


Input: Since the' omics revolution', the assessment of toxic chemical mixtures has incorporated approaches where phenotypic endpoints are connected to a mechanistic understanding of toxicity.


Input: In this study we determined the effect of binary mixtures of cadmium and phenanthrene on the reproduction of Folsomia candida and investigated the cellular mechanisms underlying this response.

cadmium

phenanthrene


Input: Mixture toxicity modeling showed an antagonistic deviation from concentration addition for reproduction effects of the mixtures.


Input: Subsequent transcriptional response analysis was done using five mixtures at the modeled 50% effect level for reproduction.


Input: The transcription profiles of 86 high throughput RT-qPCR assays were studied by means of partial least squares regression analysis.


Input: The first and second principal components (PCs) were correlated with global responses to cadmium and phenanthrene, while correlations with the mixture treatments were found in the higher PCs.

cadmium

phenanthrene


Input: Specifically associated with the mixture treatments were a biotransformation phase II gene, four mitochondrial related genes and a gene involved in the biosynthesis of antioxidant selenoproteins.


Input: Membrane integrity related gene inductions were correlated with the single phenanthrene treatment but not with the mixtures.

phenanthrene


Input: Immune and inflammatory response assays did not correlate with any of the mixtures.


Input: These results suggest moderated oxidative stress, a higher mitochondrial maintenance and less compromised membrane function in the mixture exposed samples compared to the separate cadmium or phenanthrene exposures.

cadmium

phenanthrene


Input: The antagonism found for inhibition of reproduction may partially originate from these differences.


Input: Mechanistic studies on mixture toxicity can ultimately aid risk assessment by defining relevant toxicity pathways in organisms exposed to real-world mixture exposures present in the field.


Input: High Purity Isolation and Quantification of Semiconducting Carbon Nanotubes via Column Chromatography.

Carbon


Input: The isolation of semiconducting carbon nanotubes (CNTs) to ultrahigh (ppb) purity is a prerequisite for their integration into high-performance electronic devices.

carbon


Input: Here, a method employing column chromatography is used to isolate semiconducting nanotubes to 99. 9% purity.


Input: The study finds that by modifying the solution preparation step, both the metallic and semiconducting fraction are resolved and elute using a single surfactant system, allowing for multiple iterations.


Input: Iterative processing enables a far more rapid path to achieving the level of purities needed for high performance computing.


Input: After a single iteration, the metallic peak in the absorption spectra is completely attenuated.


Input: Although absorption spectroscopy is typically used to characterize CNT purity, it is found to be insufficient in quantifying solutions of high purity (> 98 to 99%) due to low signal-to-noise in the metallic region of ultrahigh purity solutions.


Input: Therefore, a high throughput electrical testing method was developed to quantify the degree of separation by characterizing ~ 4000 field-effect transistors fabricated from the separated nanotubes after multiple iterations of the process.


Input: The separation and characterization methods described here provide a path to produce the ultrahigh purity semiconducting CNT solutions needed for high performance electronics.


Input: Influence of gas phase equilibria on the chemical vapor deposition of graphene.

graphene


Input: We have investigated the influence of gas phase chemistry on the chemical vapor deposition of graphene in a hot wall reactor.

graphene


Input: A new extended parameter space for graphene growth was defined through literature review and experimentation at low pressures (>= 0. 001 mbar).

graphene


Input: The deposited films were characterized by scanning electron microscopy, Raman spectroscopy, and dark field optical microscopy, with the latter showing promise as a rapid and nondestructive characterization technique for graphene films.

graphene


Input: The equilibrium gas compositions have been calculated across this parameter space.


Input: Correlations between the graphene films grown and prevalent species in the equilibrium gas phase revealed that deposition conditions associated with a high acetylene equilibrium concentration lead to good quality graphene deposition, and conditions that stabilize large hydrocarbon molecules in the gas phase result in films with multiple defects.

graphene

acetylene

graphene

hydrocarbon


Input: The transition between lobed and hexagonal graphene islands was found to be linked to the concentration of the monatomic hydrogen radical, with low concentrations associated with hexagonal islands.

graphene

hydrogen


Input: UVA Radiation Induced Ultrafast Electron Transfer from a Food Carcinogen Benzo [a] pyrene to Organic Molecules, Biological Macromolecules, and Inorganic Nano Structures.

Benzo [a] pyrene


Input: Reactions involving electron transfer (ET) and reactive oxygen species (ROS) play a pivotal role in carcinogenesis and cancer biochemistry.

oxygen


Input: Our present study emphasizes UVA radiation induced ET reaction as one of the key aspects of a potential carcinogen, benzo [a] pyrene (BP), in the presence of a wide variety of molecules covering organic p-benzoquinone (BQ), biological macromolecules like calf-thymus DNA (CT-DNA), human serum albumin (HSA) protein, and inorganic zinc oxide (ZnO) nanorods (NRs).

benzo [a] pyrene

p-benzoquinone

zinc oxide

ZnO


Input: Steady-state and picosecond-resolved fluorescence spectroscopy have been used to monitor such ET reactions.


Input: Physical consequences of BP association with CT-DNA have been investigated through temperature-dependent circular dichroism (CD) spectroscopy.


Input: The temperature-dependent steady-state, picosecond-resolved fluorescence lifetime and anisotropy studies reveal the effect of temperature on the perturbation of such ET reactions from BP to biological macromolecules, highlighting their temperature-dependent association.


Input: Furthermore, the electron-donating property of BP has been corroborated by measuring wavelength-dependent photocurrent in a BP-anchored ZnO NR-based photodevice, offering new physical insights for the carcinogenic study of BP.

ZnO


Input: Effect of sequence on the ionization behavior of a series of amphiphilic polypeptides.


Input: The behavior of five polypeptides made of hydrophilic and pH-responsive aspartic acid (Asp) and hydrophobic phenylalanine (Phe), which had been prepared by stitching together short well-defined sequences of Asp and Phe, was studied as a function of pH.

aspartic acid

Asp

phenylalanine

Phe

Asp

Phe


Input: The effect of pH on these polypeptides referred to as (Asp3Phe1) n, (Asp2Phe1) n, (Asp1Phe1) n, (Asp1Phe2) n, and (Asp1Phe3) n varied dramatically depending on their constituting sequence.


Input: The more hydrophobic polypeptides (Asp1Phe2) n and (Asp1Phe3) n behaved as if the Asp' s were isolated from each other and showed an apparent pKa (pKa (app)) that remained constant with level of ionization (alpha = [Asp (-)]/[Asp] total) and equaled 5. 4 and 6. 4, respectively.

Asp


Input: The more hydrophilic polypeptides (Asp3Phe1) n and (Asp2Phe1) n behaved like weak polyacids showing a linear increase in pKa (app) with increasing alpha.


Input: The pKa (app) of (Asp1Phe1) n showed a trend as a function of alpha intermediate between the Asp-rich and Phe-rich polypeptides, behaving as if the Asp' s were isolated at low alpha values (< 0. 35) but acting as a weak polyacid for large alpha values (> 0. 35).

Asp


Input: The effect that alpha, and thus the charge density of the polypeptides, had on the collapse and aggregation of the polypeptides was characterized by conducting static light scattering and fluorescence measurements.


Input: Static light scattering measurements demonstrated that all polypeptides precipitated and aggregated in solution at a critical charge density of 0. 2.


Input: Fluorescence measurements with pyrene indicated that this behavior was due to the formation of Phe aggregates in water.

pyrene

Phe


Input: Together, these experiments provide a complete description of how pH affects the behavior of a series of unique amphiphilic polypeptides designed with a well-defined sequence.


Input: Preferential adsorption and activity of monocomponent cellulases on lignocellulose thin films with varying lignin content.


Input: Understanding the enzymatic hydrolysis of cellulose and the influence of lignin in the process are critical for viable production of fuels and chemicals from lignocellulosic biomass.


Input: The interactions of monocomponent cellulases with cellulose and lignin substrates were investigated by using thin films supported on quartz crystal microgravimetry (QCM) resonators.

quartz


Input: Trichoderma reesei exoglucanase (CBH-I) and endoglucanase (EG-I) bound strongly to both cellulose and lignin but EG-I exhibited a distinctive higher affinity with lignin, causing a more extensive inhibition of the cellulolytic reactions.


Input: CBH-I was found to penetrate into the bulk of the cellulose substrate increasing the extent of hydrolysis and film deconstruction.


Input: In the absence of a cellulose binding domain (CBD) and a linker, the CBH-I core adsorbed slowly and was not able to penetrate into the film.


Input: Conversely to CBH-I, EG-I exhibited activity only on the surface of the lignocellulose substrate even when containing a CBD and a linker.


Input: Interestingly, EG-I displayed a clearly different interaction profile as a function of contact time registered by QCM.


Input: Conformation Guides Molecular Efficacy in Docking Screens of Activated beta-2 Adrenergic G Protein Coupled Receptor.


Input: A prospective, large library virtual screen against an activated beta 2-adrenergic receptor (beta 2AR) structure returned potent agonists to the exclusion of inverse-agonists, providing the first complement to the previous virtual screening campaigns against inverse-agonist-bound G protein coupled receptor (GPCR) structures, which predicted only inverse-agonists.


Input: In addition, two hits recapitulated the signaling profile of the co-crystal ligand with respect to the G protein and arrestin mediated signaling.


Input: This functional fidelity has important implications in drug design, as the ability to predict ligands with predefined signaling properties is highly desirable.


Input: However, the agonist-bound state provides an uncertain template for modeling the activated conformation of other GPCRs, as a dopamine D2 receptor (DRD2) activated model templated on the activated beta 2AR structure returned few hits of only marginal potency.

dopamine


Input: Postsynthesis modification of a porous coordination polymer by LiCl To enhance H + transport.

LiCl

H +


Input: A Ca (2 +) porous coordination polymer with 1D channels was functionalized by the postsynthesis addition of LiCl to enhance the H (+) conductivity.

Ca (2 +)

LiCl

H (+)


Input: The compound showed over 10 (-2) S cm (-1) at 25 degrees C and 20% relative humidity.


Input: Pulse-field gradient NMR elucidated that the fast H (+) conductivity was achieved by the support of Li (+) ion movements in the channel.

H (+)

Li (+)


Input: Hieranoid: Hierarchical Orthology Inference.


Input: An accurate inference of orthologs is essential in many research fields such as comparative genomics, molecular evolution, and genome annotation.


Input: Existing methods for genome-scale orthology inference are mostly based on all-versus-all similarity searches that scale quadratically with the number of species.


Input: This limits their application to the increasing number of available large-scale datasets.


Input: Here, we present Hieranoid, a new orthology inference method using a hierarchical approach.


Input: Hieranoid performs pairwise orthology analysis using InParanoid at each node in a guide tree as it progresses from its leaves to the root.


Input: This concept reduces the total runtime complexity from a quadratic to a linear function of the number of species.


Input: The tree hierarchy provides a natural structure in multi-species ortholog groups, and the aggregation of multiple sequences allows for multiple alignment similarity searching techniques, which can yield more accurate ortholog groups.


Input: Using the recently published orthobench benchmark, Hieranoid showed the overall best performance.


Input: Our progressive approach presents a new way to infer orthologs that combines efficient graph-based methodology with aspects of compute-intensive tree-based methods.


Input: The linear scaling with the number of species is a major advantage for large-scale applications and makes Hieranoid well suited to cope with vast amounts of sequenced genomes in the future.


Input: Hieranoid is an open source and can be downloaded at Hieranoid. sbc. su. se.


Input: Effect of iontophoresis on the in vitro trans-scleral transport of three single stranded oligonucleotides.


Input: Oligonucleotides represent a subject of clinical interest due to their potential ability to treat several diseases, including those affecting the posterior segment of the eye.


Input: Unfortunately, therapeutic oligonucleotides are currently administered by means of highly invasive approaches, such as intravitreal injections.


Input: The aim of the present work was to study in vitro, across isolated bovine sclera, the effect of iontophoresis on the transport of three single stranded oligonucleotides (ssDNA), 12-, 24-and 36-mer, selected as reference compounds in view of a non-invasive drug delivery to the back of the eye.


Input: All the three sequences were able to cross bovine sclera in vitro without iontophoresis.


Input: When anodal iontophoresis was applied, no change in flux was observed, while in the presence of cathodal iontophoresis the permeability coefficients increased four-fold compared to passive conditions.


Input: This behavior can be ascribed to the electrorepulsive mechanism, due to the negative charge of the nucleic acid backbone.


Input: It was also observed that the molecular weights of the three sequences did not affect trans-scleral transport, neither in passive, nor in current assisted permeation.


Input: Furthermore, increasing the current intensity from 1. 75mA to 3mA, no effect on the trans-scleral transport of the 24-mer was noticed.


Input: Although preliminary, the results demonstrate that cathodal iontophoresis enhances trans-scleral transport of single stranded oligonucleotides and suggest its use as a novel non-invasive approach for the treatment of diseases affecting the posterior segment of the eye.


Input: Activity-based assay for human mono-ADP-ribosyltransferases ARTD7/PARP15 and ARTD10/PARP10 aimed at screening and profiling inhibitors.

ADP


Input: Poly (ADP-ribose) polymerases (PARPs) or diphtheria toxin like ADP-ribosyl transferases (ARTDs) are enzymes that catalyze the covalent modification of proteins by attachment of ADP-ribose units to the target amino acid residues or to the growing chain of ADP-ribose.

Poly (ADP-ribose)

ADP

ribosyl

ADP

ribose

amino acid

ADP

ribose


Input: A subclass of the ARTD superfamily consists of mono-ADP-ribosyl transferases that are thought to modify themselves and other substrate proteins by covalently adding only a single ADP-ribose moiety to the target.

ADP

ribosyl

ADP

ribose


Input: Many of the ARTD enzymes are either established or potential drug targets and a functional activity assay for them will be a valuable tool to identify selective inhibitors for each enzyme.


Input: Existing assays are not directly applicable for screening of inhibitors due to the different nature of the reaction and different target molecules.


Input: We modified and applied a fluorescence-based assay previously described for PARP1/ARTD1 and tankyrase/ARTD5 for screening of PARP10/ARTD10 and PARP15/ARTD7 inhibitors.


Input: The assay measures the amount of NAD (+) present after chemically converting it to a fluorescent analog.

NAD (+)


Input: We demonstrate that by using an excess of a recombinant acceptor protein the performance of the activity-based assay is excellent for screening of compound libraries.


Input: The assay is homogenous and cost effective, making it possible to test relatively large compound libraries.


Input: This method can be used to screen inhibitors of mono-ARTDs and profile inhibitors of the enzyme class.


Input: The assay was optimized for ARTD10 and ARTD7, but it can be directly applied to other mono-ARTDs of the ARTD superfamily.


Input: Profiling of known ARTD inhibitors against ARTD10 and ARTD7 in a validatory screening identified the best inhibitors with submicromolar potencies.


Input: Only few of the tested ARTD inhibitors were potent, implicating that there is a need to screen new compound scaffolds.


Input: This is needed to create small molecules that could serve as biological probes and potential starting points for drug discovery projects against mono-ARTDs.


Input: Multifunctional pH-sensitive superparamagnetic iron-oxide nanocomposites for targeted drug delivery and MR imaging.

iron-oxide


Input: A multifunctional pH-sensitive superparamagnetic iron-oxide (SPIO) nanocomposite system was developed for simultaneous tumor magnetic resonance imaging (MRI) and therapy.

iron-oxide


Input: Small-size SPIO nanoparticles were chemically bonded with antitumor drug doxorubicin (DOX) and biocompatible poly (ethylene glycol) (PEG) through pH-sensitive acylhydrazone linkages, resulting in the formation of SPIO nanocomposites with magnetic targeting and pH-sensitive properties.

doxorubicin

DOX

poly (ethylene glycol)

PEG

acylhydrazone


Input: These DOX-conjugated SPIO nanocomposites exhibited not only good stability in aqueous solution but also high saturation magnetizations.

DOX


Input: Under an acidic environment, the DOX was quickly released from the SPIO nanocomposites due to the cleavage of pH-sensitive acylhydrazone linkages.

DOX


Input: With the help of magnetic field, the DOX-conjugated SPIO nanocomposites showed high cellular uptake, indicating their magnetic targeting property.

DOX


Input: Comparing to free DOX, the DOX-conjugated SPIO nanocomposites showed better antitumor effect under magnetic field.

DOX

DOX


Input: At the same time, the relaxivity value of these SPIO nanocomposites was higher than 146s (-1) mM (-1) Fe, leading to ~ 4 times enhancement compared to that of free SPIO nanoparticles.

Fe


Input: As a negative contrast agent, these SPIO nanocomposites illustrated high resolution in MRI diagnosis of tumor-bearing mice.


Input: All of these results confirm that these pH-sensitive SPIO nanocomposites are promising hybrid materials for synergistic MRI diagnosis and tumor therapy.


Input: Effectiveness of albumin-conjugated gossypol as an immunogen to prevent gossypol-associated acute hepatotoxicity in rats.

gossypol

gossypol


Input: Gossypol is a highly reactive compound present in cotton (Gossypium spp.).

Gossypol


Input: The aim of this work was to determine whether the administration of gossypol conjugated to albumin can immunize rats and thereby prevent the acute hepatotoxicity associated with gossypol.

gossypol

gossypol


Input: The first experiment consisted of administering the immunogen gossypol-BSA, with or without the Freund' s incomplete adjuvant, to rats.

gossypol


Input: The production of antibodies against gossypol was subsequently verified.

gossypol


Input: The second experiment comprised three groups of Wistar rats: VG, CG and CO.


Input: The rats from the VG cohort were injected with gossypol-BSA associated with Freund' s incomplete adjuvant, and the animals from the CG and CO groups were injected with saline solution.

gossypol


Input: After 21days, the rats from the VG and CG cohorts were treated with 30mg/kg of gossypol by intraperitoneal injection, whereas the rats from the CO group received corn oil.

gossypol


Input: After 24h, the rats were evaluated for clinical signs of pathology, and their serum was biochemically analyzed.


Input: It was found that gossypol promoted hepatotoxic effects that were not prevented by the administration of gossypol-BSA.

gossypol

gossypol


Input: In conclusion, the administration of gossypol-BSA associated with Freund' s incomplete adjuvant may be lightly to prevent the acute hepatotoxicity associated with gossypol.

gossypol

gossypol


Input: A Rice Immunophilin Gene, OsFKBP16-3, Confers Tolerance to Environmental Stress in Arabidopsis and Rice.


Input: The putative thylakoid lumen immunophilin, FKBP16-3, has not yet been characterized, although this protein is known to be regulated by thioredoxin and possesses a well-conserved CxxxC motif in photosynthetic organisms.


Input: Here, we characterized rice OsFKBP16-3 and examined the role of this gene in the regulation of abiotic stress in plants.


Input: FKBP16-3s are well conserved in eukaryotic photosynthetic organisms, including the presence of a unique disulfide-forming CxxxC motif in their N-terminal regions.

disulfide

N


Input: OsFKBP16-3 was mainly expressed in rice leaf tissues and was upregulated by various abiotic stresses, including salt, drought, high light, hydrogen peroxide, heat and methyl viologen.

hydrogen peroxide

methyl viologen


Input: The chloroplast localization of OsFKBP16-3-GFP was confirmed through the transient expression of OsFKBP16-3 in Nicotiana benthamiana leaves.


Input: Transgenic Arabidopsis and transgenic rice plants that constitutively expressed OsFKBP16-3 exhibited increased tolerance to salinity, drought and oxidative stresses, but showed no change in growth or phenotype, compared with vector control plants, when grown under non-stressed conditions.


Input: This is the first report to demonstrate the potential role of FKBP16-3 in the environmental stress response, which may be regulated by a redox relay process in the thylakoid lumen, suggesting that artificial regulation of FKBP16-3 expression is a candidate for stress-tolerant crop breeding.


Input: Modeling distinct osteosarcoma subtypes in vivo using Cre: lox and lineage-restricted transgenic shRNA.


Input: Osteosarcoma is the most common primary cancer of bone and one that predominantly affects children and adolescents.


Input: Osteoblastic osteosarcoma represents the major subtype of this tumor, with approximately equal representation of fibroblastic and chondroblastic subtypes.


Input: We and others have previously described murine models of osteosarcoma based on osteoblast-restricted Cre: lox deletion of Trp53 (p53) and Rb1 (Rb), resulting in a phenotype most similar to fibroblastic osteosarcoma in humans.


Input: We now report a model of the most prevalent form of human osteosarcoma, the osteoblastic subtype.


Input: In contrast to other osteosarcoma models that have used Cre: lox mediated gene deletion, this model was generated through shRNA-based knockdown of p53.


Input: As is the case with the human disease the shRNA tumors most frequently present in the long bones and preferentially disseminate to the lungs; feature less consistently modeled using Cre: lox approaches.


Input: Our approach allowed direct comparison of the in vivo consequences of targeting the same genetic drivers using two different technologies, Cre: lox and shRNA.


Input: This demonstrated that the effects of Cre: lox and shRNA mediated knock-down are qualitatively different, at least in the context of osteosarcoma, and yielded distinct subtypes of osteosarcoma.


Input: Through the use of complementary genetic modification strategies we have established a model of the most common clinical subtype of osteosarcoma that was not previously represented and more fully recapitulated the clinical spectrum of this cancer.


Input: Eliciting preferences for priority setting in genetic testing: a pilot study comparing best-worst scaling and discrete-choice experiments.


Input: Given the increasing number of genetic tests available, decisions have to be made on how to allocate limited health-care resources to them.


Input: Different criteria have been proposed to guide priority setting.


Input: However, their relative importance is unclear.


Input: Discrete-choice experiments (DCEs) and best-worst scaling experiments (BWSs) are methods used to identify and weight various criteria that influence orders of priority.


Input: This study tests whether these preference eliciting techniques can be used for prioritising genetic tests and compares the empirical findings resulting from these two approaches.


Input: Pilot DCE and BWS questionnaires were developed for the same criteria: prevalence, severity, clinical utility, alternatives to genetic testing available, infrastructure for testing and care established, and urgency of care.


Input: Interview-style experiments were carried out among different genetics professionals (mainly clinical geneticists, researchers and biologists).


Input: A total of 31 respondents completed the DCE and 26 completed the BWS experiment.


Input: Weights for the levels of the six attributes were estimated by conditional logit models.


Input: Although the results derived from the DCE and BWS experiments differed in detail, we found similar valuation patterns in the DCE and BWS experiments.


Input: The respondents attached greatest value to tests with high clinical utility (defined by the availability of treatments that reduce mortality and morbidity) and to testing for highly prevalent conditions.


Input: The findings from this study exemplify how decision makers can use quantitative preference eliciting methods to measure aggregated preferences in order to prioritise alternative clinical interventions.


Input: Further research is necessary to confirm the survey results. European Journal of Human Genetics advance online publication, 13 March 2013; doi: 10. 1038/ejhg. 2013. 36.


Input: Two Dimensional Window Exchange Umbrella Sampling for Transmembrane Helix Assembly.


Input: The method of window exchange umbrella sampling molecular dynamics (WEUSMD) with a pre-optimized parameter set was recently used to obtain the most probable conformations and the energetics of transmembrane (TM) helix assembly of a generic TM sequence.


Input: When applied to glycophorin A TM domain (GpA-TM) using the restraint potentials along the helix-helix distance, however, tight interfacial packing of GpA-TM resulted in insufficient conformational sampling at short helix-helix separation.


Input: This sampling issue is addressed by extending the WEUSMD into two dimensions with the restraint potentials along the helix-helix distance and crossing angle.


Input: The two-dimensional WEUSMD results demonstrate that the incomplete sampling in the one-dimensional WEUSMD arises from high barriers along the crossing angle between the GpA-TM helices.


Input: Together with the faster convergence in both the assembled conformations and the potential of mean force, the 2D-WEUSMD can be a general and efficient approach in computational studies of TM helix assembly.


Input: Rotational spectroscopy meets theory.


Input: Rotational spectroscopy is known to be a technique that is widely used to infer information on molecular structure and dynamics.


Input: In the last few decades, its role in the field of atmospheric and astrophysical investigations has rapidly grown.


Input: However, several are the challenging aspects in rotational spectroscopy, since the detection and analysis of spectra as well as interpretation of obtained results are not at all straightforward.


Input: Quantum chemistry has reached such an accuracy that can be used to disentangle these challenging situations by guiding the experimental investigation, assisting in the determination of the spectroscopic parameters, and extracting information of chemical interest.


Input: This perspective provides an overview of the theoretical background and computational requirements needed for the accurate evaluation of the spectroscopic parameters of relevance to rotational spectroscopy.


Input: The role of theory in guiding and supporting experiment is detailed through a few examples, and the interplay of experiment and theory is discussed in terms of the information of physical and chemical interest that can be derived.


Input: Effects of progesterone and medroxyprogesterone on actin remodeling and neuronal spine formation.

progesterone

medroxyprogesterone


Input: Sex steroids are important regulators of neuronal cell morphology, and this is critical for gender differences in brain function and dysfunction.

steroids


Input: Neuronal morphology is controlled by multiprotein complexes including moesin (a member of the ezrin/radixin/moesin family), focal adhesion kinase (FAK), or the Wiskott-Aldrich syndrome protein-family verprolin homologous (WAVE1) protein, controlling dynamic remodeling of the cytoskeleton and cell membrane.


Input: We investigated the actions of natural progesterone (P) and of the synthetic progestin medroxyprogesterone acetate (MPA) on actin remodeling, focal adhesion complex formation, and actin branching in rat cortical neurons.

progesterone

progestin medroxyprogesterone acetate

MPA


Input: Treatment with P and, to a lesser extent, MPA, increases the number and density of dendritic spines.

MPA


Input: P increases the phosphorylation of moesin, FAK, and WAVE1, and their redistribution toward cell membrane sites where spines are formed.


Input: Signaling to moesin is achieved by PR via a G alpha/G beta-dependent signaling to the small GTPase Ras homolog gene family, member A and its related kinase, Rho-associated kinase-2.


Input: In parallel, WAVE1 recruitment is triggered by a G alpha i/G beta-dependent signaling of PR to c-Src, FAK, and Rac1 GTPase.


Input: Rac1 recruits cyclin-dependent kinase-5, which phosphorylates WAVE1.


Input: Silencing of moesin, FAK, or WAVE1 abrogates the increase in dendritic spines induced by progesterone.

progesterone


Input: In all applications, MPA is found to act similar to P, albeit with a lower efficacy.

MPA


Input: In conclusion, our findings indicate that the control of actin polymerization and branching and focal adhesion complex formation via moesin, FAK, and WAVE1 is a key function of progesterone receptor in neurons, which may be relevant for the regulation of dendritic spine turnover and neuronal plasticity.

progesterone


Input: Gold nanoparticles on oxide-free silicon-molecule interface for single electron transport.

oxide

silicon


Input: Two different organic monolayers were prepared on silicon Si (111) and modified for attaching gold nanoparticles.

silicon Si (111)


Input: The molecules are covalently bound to silicon and form very ordered monolayers sometimes improperly called self-assembled monolayers (SAM).

silicon


Input: They are designed to be electrically insulating and to have very few electrical interface states.


Input: By positioning the tip of an STM above a nanoparticle, a double barrier tunnel junction (DBTJ) is created, and Coulomb blockade is demonstrated at 40 K.


Input: This is the first time Coulomb blockade is observed with an organic monolayer on oxide-free silicon.

silicon


Input: This work focuses on the fabrication and initial electrical characterization of this double barrier tunnel junction.


Input: The organic layers were prepared by thermal hydrosilylation of two different alkene molecules with either a long carbon chain (C11) or a shorter one (C7), and both were modified to be amine-terminated.

carbon

amine


Input: FTIR and XPS measurements confirm that the Si (111) substrate remains unoxidized during the whole chemical process.

Si (111)


Input: Colloidal gold nanoparticles were prepared using two methods: either with citrate molecules (Turkevich method) or with ascorbic acid as the surfactant.

citrate

ascorbic acid


Input: In both cases AFM and STM images show a well-controlled deposition on the grafted organic monolayer.


Input: I-V curves obtained by scanning tunneling spectroscopy (STS) are presented on 8 nm diameter nanoparticles and exhibit the well-known Coulomb staircases at low temperature.


Input: The curves are discussed as a function of the organic layer thickness and silicon substrate doping.


Input: Nanodiamond nanofluids for enhanced thermal conductivity.


Input: Deaggregation of oxidized ultradispersed diamond (UDD) in dimethylsulfoxide followed by reaction with glycidol monomer, purification via aqueous dialysis, and dispersion in ethylene glycol (EG) base fluid affords nanodiamond (ND)-poly (glycidol) polymer brush: EG nanofluids exhibiting 12% thermal conductivity enhancement at a ND loading of 0. 9 vol%.

diamond

dimethylsulfoxide

glycidol

ethylene glycol

poly (glycidol)


Input: Deaggregation of UDD in the presence of oleic acid/octane followed by dispersion in light mineral oil and evaporative removal of octane gives ND. oleic acid: mineral oil dispersions exhibiting 11% thermal conductivity enhancement at a ND loading of 1. 9 vol%.

oleic acid

octane

octane

oleic acid


Input: Average particle sizes of ND additives, determined by dynamic light scattering, are, respectively, ca.


Input: 11 nm (in H2O) and 18 nm (in toluene).

toluene


Input: Observed thermal conductivity enhancements outperform enhancement effects calculated using Maxwell' s effective medium approximation by 2-to 4-fold.


Input: Covalent ND surface modification gives 2-fold greater thermal conductivity enhancement than ND surface modification via hydrogen-bonding interactions at similar concentrations.

hydrogen


Input: Stable, static ND: mineral oil dispersions are reported for the first time.


Input: Molecular dynamics simulation of nanosized water droplet spreading in an electric field.


Input: Molecular dynamics (MD) simulations are performed for the spreading of a nanosized water droplet on a solid substrate subject to a parallel electric field.


Input: A combined electrostatic and Lennard-Jones potential is employed to represent the intermolecular interactions.


Input: Results show that in response to the applied field, polar water molecules realign themselves and this microscopic reorientation of molecular dipoles combines with the intermolecular forces to produce a macroscopic deformation of a free spherical water droplet into an ellipsoid.


Input: The applied field has a strong effect on the spreading of the water droplet on a solid substrate.


Input: For a weaker parallel field, the droplet spreading is asymmetric with the leading contact angle being greater than the trailing contact angle.


Input: With an increase in field strength, this asymmetry continues to increase, culminates, and then decreases until it disappears.


Input: The symmetric spreading remains with a further increase in the field strength until the saturation point is reached.


Input: This transition from the asymmetric to symmetric spreading is a manifestation of the interaction of the electric field with polar water molecules and the intermolecular forces within the droplet and between the water and solid; the interaction also leads to a change in hydrogen bonds along the droplet surface.

hydrogen


Input: The dynamics of the droplet spreading is entailed by the electrically induced motion of molecules along the liquid surface toward the solid substrate and is controlled by a competing mechanism among the electric, water-water, and water-solid intermolecular forces.


Input: Enzymatic Conversion of 6-Nitroquinoline to the Fluorophore 6-Aminoquinoline Selectively under Hypoxic Conditions.


Input: There is substantial interest in small molecules that can be used to detect or kill the hypoxic (low oxygen) cells found in solid tumors.

oxygen


Input: Nitroaryl moieties are useful components in the design of hypoxia-selective imaging agents and prodrugs because one-electron reductases can convert the nitroaryl group to nitroso, hydroxylamino, and amino metabolites selectively under low oxygen conditions.

Nitroaryl

nitroaryl

nitroso

hydroxylamino

amino

oxygen


Input: Here, we describe the in vitro, cell free metabolism of a pro-fluorescent substrate, 6-nitroquinoline (1) under both aerobic and hypoxic conditions.


Input: Both LC-MS and fluorescence spectroscopic analyses provided evidence that the one-electron reducing enzyme system, xanthine/xanthine oxidase, converted the nonfluorescent parent compound 1 to the known fluorophore 6-aminoquinoline (2) selectively under hypoxic conditions.

xanthine

xanthine


Input: The presumed intermediate in this reduction process, 6-hydroxylaminoquinoline (6), is fluorescent and can be efficiently converted by xanthine/xanthine oxidase to 2 only under hypoxic conditions.

xanthine

xanthine


Input: This finding provides evidence for multiple oxygen-sensitive steps in the enzymatic conversion of nitroaryl compounds to the corresponding amino derivatives.

oxygen

nitroaryl

amino


Input: In a side reaction that is separate from the bioreductive metabolism of 1, xanthine oxidase converted 1 to 6-nitroquinolin-2 (1H)-one (5).

xanthine

6-nitroquinolin-2 (1H)-one


Input: These studies may enable the use of 1 as a fluorescent substrate for the detection and profiling of one-electron reductases in cell culture or biopsy samples.


Input: In addition, the compound may find use as a fluorogenic probe for the detection of hypoxia in tumor models.


Input: The occurrence of side products such as 5 in the enzymatic bioreduction of 1 underscores the importance of metabolite identification in the characterization of hypoxia-selective probes and drugs that employ nitroaryl units as oxygen sensors.

nitroaryl

oxygen


Input: Comparative antimalarial activities and ADME profiles of ozonides (1, 2, 4-trioxolanes) OZ277, OZ439, and their 1, 2-dioxolane, 1, 2, 4-trioxane, and 1, 2, 4, 5-tetraoxane isosteres.

ozonides

1, 2, 4-trioxolanes

1, 2-dioxolane

1, 2, 4-trioxane

1, 2, 4, 5-tetraoxane


Input: To ascertain the structure-activity relationship of the core 1, 2, 4-trioxolane substructure of dispiro ozonides OZ277 and OZ439, we compared the antimalarial activities and ADME profiles of the 1, 2-dioxolane, 1, 2, 4-trioxane, and 1, 2, 4, 5-tetraoxane isosteres.

1, 2, 4-trioxolane

dispiro ozonides OZ277

1, 2-dioxolane

1, 2, 4-trioxane

1, 2, 4, 5-tetraoxane


Input: Consistent with previous data, both dioxolanes had very weak antimalarial properties.

dioxolanes


Input: For the OZ277 series, the trioxane isostere had the best ADME profile, but its overall antimalarial efficacy was not superior to that of the trioxolane or tetraoxane isosteres.

trioxane

trioxolane

tetraoxane


Input: For the OZ439 series, there was a good correlation between the antimalarial efficacy and ADME profiles in the rank order trioxolane > trioxane > tetraoxane.

trioxolane

trioxane

tetraoxane


Input: As we have previously observed for OZ439 versus OZ277, the OZ439 series peroxides had superior exposure and efficacy in mice compared to the corresponding OZ277 series peroxides.

peroxides

peroxides


Input: Cardiovascular safety of the dipetidyl peptidase-4 inhibitor alogliptin in type 2 diabetes mellitus (+)

alogliptin


Input: AIM: As there have been concerns that some classes or agents for the treatment of type 2 diabetes may increase CV risk, we evaluated the cardiovascular profile of the dipeptidyl peptidase-4 inhibitor alogliptin.

alogliptin


Input: METHODS: We evaluated the incidence of CV events in patients treated with alogliptin, placebo or comparator antihyperglycaemic drugs in the clinical trial database for alogliptin using the composite major adverse cardiovascular event (MACE) endpoints of CV death, non-fatal myocardial infarction and non-fatal stroke.

alogliptin

alogliptin


Input: RESULTS: The pooled analysis included 4168 patients exposed to alogliptin 12. 5 and 25 mg daily for 2023 patient-years compared to 691 patients treated with placebo for 263 patient-years and 1169 patients treated with other antidiabetic agents (metformin, sulfonylureas and thiazolidinediones) for 703 patient-years.

alogliptin

metformin

sulfonylureas

thiazolidinediones


Input: CV events were adjudicated by an expert endpoint committee blinded to treatment allocation.


Input: The incidence rates of the combined MACE were not significantly different between patients treated with alogliptin and comparator therapies (hazard ratio = 0. 635, 95% confidence interval, 0. 0, 1. 41).

alogliptin


Input: Additionally, other types of serious CV events were not significantly different between patients treated with alogliptin and comparator therapies.

alogliptin


Input: CONCLUSION: These analyses have not shown a signal of increased CV risk with alogliptin in patients with type 2 diabetes.

alogliptin


Input: Future results from the adequately powered EXAMINE trial will definitively assess the CV safety profile of aloglipin in patients with type 2 diabetes mellitus.

aloglipin


Input: Synthesis of (R)-norbgugaine and its potential as quorum sensing inhibitor against Pseudomonas aeruginosa.

(R)-norbgugaine


Input: (R)-Bgugaine is a natural pyrrolidine alkaloid from Arisarum vulgare, which shows antifungal and antibacterial activity.

(R)-Bgugaine

pyrrolidine alkaloid


Input: In this Letter, we have accomplished the simple synthesis of norbgugaine (demethylated form of natural bgugaine) employing Wittig olefination and cat. hydrogenation as the key steps and its biological studies are reported for the first time.

norbgugaine

bgugaine


Input: The synthesized norbgugaine was evaluated for inhibition of quorum sensing mediated virulence factors (motility, biofilm formation, pyocyanin pigmentation, rhamnolipid production and LasA protease) in Pseudomonas aeruginosa wherein swarming motility is reduced by 95%, and biofilm formation by 83%.

norbgugaine

pyocyanin


Input: Novel small molecules as apoptosis inducers: synthesis, preliminary structure-activity relationships, and in vitro biological evaluation.


Input: Inducing apoptosis is a promising therapeutic approach to overcome cancer.


Input: In this study, 30 compounds were synthesized and evaluated for their antiproliferative activity against three tumor cell lines in vitro: A875, H460 and Hela cancer cells by the MTT assay.

MTT


Input: The most potent analogue 7a, a novel compound was first reported by our group, inhibited the proliferation of A875 cells with an IC50 value of 98 nM.


Input: Flow cytometry analysis and morphological analysis suggested that compound 7a had potential anticancer efficacy via G2/M cell cycle arrest, which could be attributed to its proliferation and apoptosis, and also in a concentration-dependent manner.


Input: The SAR analysis indicated that the substituents R (2) played a crucial role in the antiproliferation activity.


Input: N-(Pyridin-2-yl) arylsulfonamide inhibitors of 11 beta-hydroxysteroid dehydrogenase type 1: strategies to eliminate reactive metabolites.

N-(Pyridin-2-yl) arylsulfonamide

11 beta-hydroxysteroid


Input: N-(Pyridin-2-yl) arylsulfonamides 1 and 2 (PF-915275) were identified as potent inhibitors of 11 beta-hydroxysteroid dehydrogenase type 1.

N-(Pyridin-2-yl) arylsulfonamides

11 beta-hydroxysteroid


Input: A screen for bioactivation revealed that these compounds formed glutathione conjugates.

glutathione


Input: This communication presents the results of a risk benefit analysis carried out to progress 2 (PF-915275) to a clinical study and the strategies used to eliminate reactive metabolites in this series of inhibitors.


Input: Based on the proposed mechanism of bioactivation and structure-activity relationships, design efforts led to N-(pyridin-2-yl) arylsulfonamides such as 18 and 20 that maintained potent 11 beta-hydroxysteroid dehydrogenase type 1 activity, showed exquisite pharmacokinetic profiles, and were negative in the reactive metabolite assay.

N-(pyridin-2-yl) arylsulfonamides

11 beta-hydroxysteroid


Input: Light at Night Alters Daily Patterns of Cortisol and Clock Proteins in Female Siberian Hamsters.

Cortisol


Input: Humans and other organisms have adapted to a 24-h solar cycle in response to life on Earth.


Input: The rotation of the planet on its axis and its revolution around the sun cause predictable daily and seasonal patterns in day length.


Input: In order to successfully anticipate and adapt to these patterns in the environment, a variety of biological processes oscillate with a daily rhythm approximately 24 h in length.


Input: These rhythms arise from hierarchally-coupled cellular clocks generated by positive and negative transcription factors of core circadian clock gene expression.


Input: From these endogenous cellular clocks, overt rhythms in activity and patterns in hormone secretion and other homeostatic processes emerge.


Input: These circadian rhythms in physiology and behavior can be organized by a variety of cues, but they are most potently entrained by light.


Input: In recent history, there has been a major change from naturally occurring light cycles set by the sun, to artificial and sometimes erratic light cycles determined by the use of electric lighting.


Input: Virtually every individual living in an industrialized country experiences light at night (LAN), but despite its prevalence, the biological effects of such unnatural lighting have not been fully considered.


Input: Using female Siberian hamsters (Phodopus sungorus), we investigated the effects of chronic nightly exposure to dim light on daily rhythms in locomotor activity, serum cortisol concentrations, and brain expression of circadian clock proteins (i. e., PER1, PER2, BMAL1).

cortisol


Input: Although locomotor activity remained entrained to the light cycle, the diurnal fluctuation of cortisol concentrations was blunted and the expression patterns of clock proteins in the SCN and hippocampus were altered.

cortisol


Input: These results demonstrate that chronic exposure to dim LAN can dramatically affect fundamental cellular function and emergent physiology.


Input: (c) 2013 British Society for Neuroendocrinology.


Input: The effect of a unique halide-stabilizing residue on the catalytic properties of haloalkane dehalogenase DatA from Agrobacterium tumefaciens C58.

halide

haloalkane


Input: Haloalkane dehalogenases catalyze the hydrolysis of carbon-halogen bonds in various chlorinated, brominated and iodinated compounds.

Haloalkane

carbon

halogen


Input: These enzymes have a conserved pair of halide-stabilizing residues that are important in substrate binding and stabilization of the transition state and the halide ion product via hydrogen bonding.

halide

halide

hydrogen


Input: In all previously known haloalkane dehalogenases, these residues are either a pair of tryptophans or a tryptophan-asparagine pair.

haloalkane

tryptophans

tryptophan

asparagine


Input: The newly-isolated haloalkane dehalogenase DatA from Agrobacterium tumefaciens C58 (EC 3. 8. 1. 5) possesses a unique halide-stabilizing tyrosine residue, Y109, in place of the conventional tryptophan.

haloalkane

halide

tyrosine

tryptophan


Input: A variant of DatA with the Y109W mutation was created and the effects of this mutation on the structure and catalytic properties of the enzyme were studied using spectroscopy and pre-steady-state kinetic experiments.


Input: Quantum mechanical and molecular dynamics calculations were used to obtain a detailed analysis of the hydrogen-bonding patterns within the active sites of the wild-type and the mutant, as well as of the stabilization of the ligands as the reaction proceeds.

hydrogen


Input: Fluorescence quenching experiments suggested that replacing the tyrosine with tryptophan improves halide binding by 3. 7-fold, presumably as a result of the introduction of an additional hydrogen bond.

tyrosine

tryptophan

halide

hydrogen


Input: Kinetic analysis revealed that the mutation affected the substrate specificity of the enzyme and reduced its K0. 5 for selected halogenated substrates by a factor of 2-4, without impacting the rate-determining hydrolytic step.


Input: We conclude that DatA is the first natural haloalkane dehalogenase that stabilizes its substrate in the active site using only a single hydrogen bond, which is a new paradigm in catalysis by this enzyme family.

haloalkane

hydrogen