Input: Depending on their shapes, these nanocrystals exhibit various surface facets, and the assignments of their surface facets have routinely been used to rationalize or predict their catalytic activity in a variety of chemical transformations.


Input: Recently we discovered that for 1-dimensional (1D) nanocrystals (Au nanorods), the catalytic activity is not constant along the same side facets of single nanorods but rather differs significantly and further shows a gradient along its length, which we attributed to an underlying gradient of surface defect density resulting from their linear decay in growth rate during synthesis (Nat. Nanotechnol. 2012, 7, 237-241).

Au


Input: Here we report that this behavior also extends to 2D nanocrystals, even for a different catalytic reaction.


Input: By using super-resolution fluorescence microscopy to map out the locations of catalytic events within individual triangular and hexagonal Au nanoplates in correlation with scanning electron microscopy, we find that the catalytic activity within the flat {111} surface facet of a Au nanoplate exhibits a 2D radial gradient from the center toward the edges.

Au

Au


Input: We propose that this activity gradient results from a growth-dependent surface defect distribution.


Input: We also quantify the site-specific activity at different regions within a nanoplate: The corner regions have the highest activity, followed by the edge regions and then the flat surface facets.


Input: These discoveries highlight the spatial complexity of catalytic activity at the nanoscale as well as the interplay amid nanocrystal growth, morphology, and surface defects in determining nanocatalyst properties.


Input: Evidence for self-association of the alternative sigma factor sigma 54.


Input: Sigma factor sigma (54) has a distinct modus operandi for mediating the activation of bacterial RNA polymerase (RNAP) at promoter recognition motifs 12 and 24 bp upstream from transcription start sites.


Input: sigma (54) was thought to act as monomer in all transcription steps.


Input: However, we provide evidence that sigma (54) of Pseudomonas putida interacts stably with itself.


Input: The interface between monomers involves contacts in sigma (54) regions I and III, sequences that play key roles in the transcription activation of sigma (54)-RNAP holoenzyme.


Input: These roles include interactions with activator proteins and the-12 and-24 motifs.


Input: In particular, we detected inter-monomer contacts between region I, and between region I and the C-terminal portion of region III.

C


Input: Our results suggest a new auto-antagonistic regulatory state of sigma (54).


Input: Determinants of regioselectivity and chemoselectivity in fosfomycin resistance protein FosA from QM/MM calculations.

fosfomycin


Input: FosA is a manganese-dependent enzyme that utilizes a Mn (2 +) ion to catalyze the inactivation of the fosfomycin antibiotic by glutathione (GSH) addition.

manganese

Mn (2 +)

fosfomycin

glutathione

GSH


Input: We report a theoretical study on the catalytic mechanism and the factors governing the regioselectivity and chemoselectivity of FosA.


Input: Density functional theory (DFT) calculations on the uncatalyzed reaction give high barriers and almost no regioselectivity even when adding two water molecules to assist the proton transfer.


Input: According to quantum mechanics/molecular mechanics (QM/MM) calculations on the full solvated protein, the enzyme-catalyzed glutathione addition reaction involves two major chemical steps that both proceed in the sextet state: proton transfer from the GSH thiol group to the Tyr39 anion and nucleophilic attack by the GSH thiolate leading to epoxide ring-opening.

glutathione

GSH thiol

GSH thiolate

epoxide


Input: The second step is rate-limiting and is facilitated by the presence of the high-spin Mn (2 +) ion that functions as a Lewis acid and stabilizes the leaving oxyanion through direct coordination.

Mn (2 +)

Lewis acid


Input: The barrier for C1 attack is computed to be 8. 9 kcal/mol lower than that for C2 attack, in agreement with the experimentally observed regioselectivity of the enzyme.


Input: Further QM/MM calculations on the alternative water attack predict a concerted mechanism for this reaction, where the deprotonation of water, nucleophilic attack, and epoxide ring-opening take place via the same transition state.

epoxide


Input: The calculated barrier is 8. 3 kcal/mol higher than that for GSH attack, in line with the observed chemoselectivity of the enzyme, which manages to catalyze the addition of GSH in the presence of water molecules around its active site.

GSH

GSH


Input: The catalytic efficiency, regioselectivity, and chemoselectivity of FosA are rationalized in terms of the influence of the active-site protein environment and the different stabilization of the distorted substrates in the relevant transition states.


Input: What is the contact angle of water on graphene?

graphene


Input: Although experimental and theoretical studies have addressed the question of the wetting properties of graphene, the actual value of the contact angle of water on an isolated graphene monolayer remains unknown.

graphene

graphene


Input: While recent experimental literature indicates that the contact angle of water on graphite is in the range 90-95 degrees, it has been suggested that the contact angle on graphene may either be as high as 127 degrees or moderately enhanced in comparison with graphite.

graphite

graphene

graphite


Input: With the support of classical molecular dynamics simulations using empirical force-fields, we develop an argumentation to show that the value of 127 degrees is an unrealistic estimate and that a value of the order of 95-100 degrees should be expected.


Input: Our study establishes a connection between the variation of the work of adhesion of water on graphene-based surfaces and the interaction potential between individual water molecules and these surfaces.

graphene


Input: We show that a variation of the contact angle from 90 degrees on graphite to 127 degrees on graphene would imply that both of the first two carbon layers of graphite contribute approximately the same interaction energy with water.

graphite

graphene

carbon

graphite


Input: Such a situation is incompatible with the short-range nature of the interaction between water and this substrate.


Input: We also show that the interaction potential energy between water and the graphene-based substrates is the main contribution to the work of adhesion of water with a relative magnitude that is independent of the number of graphene layers.

graphene

graphene


Input: We introduce the idea that the remaining contribution is entropic in nature and is connected to the fluctuations in the water-substrate interaction energy.


Input: Lessons on conditional gene targeting in mouse adipose tissue.


Input: Conditional gene targeting has been extensively used for in vivo analysis of gene function in adipocyte cell biology but often with debate over the tissue specificity and the efficacy of inactivation.


Input: To directly compare the specificity and efficacy of different Cre lines in mediating adipocyte specific recombination, transgenic Cre lines driven by the adipocyte protein 2 (aP2) and adiponectin (Adipoq) gene promoters, as well as a tamoxifen-inducible Cre driven by the aP2 gene promoter (iaP2), were bred to the Rosa26R (R26R) reporter.

tamoxifen


Input: All three Cre lines demonstrated recombination in the brown and white fat pads.


Input: Using different floxed loci, the individual Cre lines displayed a range of efficacy to Cre-mediated recombination that ranged from no observable recombination to complete recombination within the fat.


Input: The Adipoq-Cre exhibited no observable recombination in any other tissues examined, whereas both aP2-Cre lines resulted in recombination in endothelial cells of the heart and nonendothelial, nonmyocyte cells in the skeletal muscle.


Input: In addition, the aP2-Cre line can lead to germline recombination of floxed alleles in ~ 2% of spermatozoa.


Input: Thus, different " adipocyte-specific " Cre lines display different degrees of efficiency and specificity, illustrating important differences that must be taken into account in their use for studying adipose biology.


Input: Regulation of mu-opioid receptors: desensitization, phosphorylation, internalization, and tolerance.


Input: Morphine and related micro-opioid receptor (MOR) agonists remain among the most effective drugs known for acute relief of severe pain.

Morphine


Input: A major problem in treating painful conditions is that tolerance limits the long-term utility of opioid agonists.


Input: Considerable effort has been expended on developing an understanding of the molecular and cellular processes that underlie acute MOR signaling, short-term receptor regulation, and the progression of events that lead to tolerance for different MOR agonists.


Input: Although great progress has been made in the past decade, many points of contention and controversy cloud the realization of this progress.


Input: This review attempts to clarify some confusion by clearly defining terms, such as desensitization and tolerance, and addressing optimal pharmacological analyses for discerning relative importance of these cellular mechanisms.


Input: Cellular and molecular mechanisms regulating MOR function by phosphorylation relative to receptor desensitization and endocytosis are comprehensively reviewed, with an emphasis on agonist-biased regulation and areas where knowledge is lacking or controversial.


Input: The implications of these mechanisms for understanding the substantial contribution of MOR signaling to opioid tolerance are then considered in detail.


Input: While some functional MOR regulatory mechanisms contributing to tolerance are clearly understood, there are large gaps in understanding the molecular processes responsible for loss of MOR function after chronic exposure to opioids.


Input: Further elucidation of the cellular mechanisms that are regulated by opioids will be necessary for the successful development of MOR-based approaches to new pain therapeutics that limit the development of tolerance.


Input: Evaluation of a Self-Administered Oral Glucose Tolerance Test.

Glucose


Input: OBJECTIVETo assess the feasibility of using a disposable, self-administered, capillary blood sampling oral glucose tolerance test (OGTT) device in a community setting. RESEARCH DESIGN AND METHODSEighteen healthy and 12 type 2 diabetic volunteers underwent six 75-g OGTTs using a prototype device in the following three settings: unaided at home (twice); unaided but observed in clinic (twice); and performed by a nurse with simultaneous laboratory glucose assays of 0-and 120-min venous plasma samples (twice).

glucose

glucose


Input: The device displayed no results.


Input: A detachable data recorder returned to the clinic provided plasma-equivalent 0-and 120-min glucose values and key parameters, including test date, start and end times, and time taken to consume the glucose drink. RESULTSThe device was universally popular with participants, was perceived as easy to use, and the ability to test at home was well-liked.

glucose

glucose


Input: Device failures meant that 0-and 120-min glucose values were obtained for only 141 (78%) of the 180 OGTTs performed, independent of setting.

glucose


Input: Device glucose measurements showed a mean bias compared with laboratory-measured values of + 0. 9 at 5. 0 mmol/L increasing to + 4. 4 at 15. 0 mmol/L.

glucose


Input: Paired device glucose values were equally reproducible across settings, with repeat testing showing no training effect regardless of setting order. CONCLUSIONSSelf-administered OGTTs can be performed successfully by untrained individuals in a community setting.

glucose


Input: With improved device reliability and appropriate calibration, this novel technology could be used in routine practice to screen people who might need a formal OGTT to confirm the presence of impaired glucose tolerance or diabetes.

glucose


Input: Synthesis and evaluation of antibacterial activity of 7-alkyloxy-4, 5-dihydro-imidazo [1, 2-a] quinoline derivatives.

7-alkyloxy-4, 5-dihydro-imidazo [1, 2-a] quinoline


Input: In this study, a series of 7-alkyloxy-4, 5-dihydro-imidazo [1, 2-a] quinoline derivatives was synthesized and tested for their antibacterial activity against various bacterial strains.

7-alkyloxy-4, 5-dihydro-imidazo [1, 2-a] quinoline


Input: Most of the compounds exhibited potential antibacterial activity against gram-negative and gram-positive bacteria.


Input: Compound 7p (7-heptyloxy-4, 5-dihydro-imidazo [1, 2-a] quinoline) was found to be the most potent inhibitor.

7-heptyloxy-4, 5-dihydro-imidazo [1, 2-a] quinoline


Input: The minimum inhibitory concentration (MIC) of compound 7p against Escherichia coli was 0. 5 mu g/mL, better than that of reference agent ciprofloxacin and amoxicillin.

ciprofloxacin

amoxicillin


Input: Furthermore, compound 7p exhibited a modest activity against several gram-negative bacterial strains at a dose range of 2-64 mu g/mL.


Input: A common LRP4 haplotype is associated with bone mineral density and hip geometry in men-data from the Odense Androgen Study (OAS).


Input: Osteoporosis is a common disease characterized by an increased susceptibility to fracture.


Input: It is a complex disorder resulting from the interaction of several polymorphisms in different genes and environmental factors.


Input: Since we recently reported a role for low density lipoprotein-related protein (LRP)-4 in monogenic disorders with bone overgrowth, we now wanted to evaluate whether genetic variation in the LRP4 gene has an effect on the susceptibility to osteoporosis in a population based cohort from the Odense Androgen Study.

Androgen


Input: We chose to genotype four common (minor allele frequency (MAF) >= 0. 05) and non-synonymous coding polymorphisms located in the extracellular region of the LRP4 protein: rs3816614 (A/g), rs2306029 (G/a), rs2306033 (C/t) and rs6485702 (G/a) (large and small characters indicate major and minor alleles, respectively).


Input: Bone mineral density (BMD) measurements of the hip, the spine and whole body as well as different hip geometry parameters were available for a total of 1404 Danish men from two age groups ([20-29 years]: n = 804; [60-74 years]: n = 600).


Input: Using linear regression analysis adjusted for age, height and weight, we found significant associations between both rs2306029 and rs6485702 and BMD at all sites except the lumbar spine.


Input: The most significant association was found with whole body BMD (p = 4. 7 x 10 (-5)).


Input: In addition, we found these two polymorphisms to be associated with different geometry parameters especially of the femoral shaft.


Input: Analysis of the two associated SNPs in the separate age groups demonstrated that most associations are only present in the youngest group of Danish men.


Input: In the group of elderly men, one Bonferroni corrected association between whole body BMD and rs6485702 was found to be significant.


Input: Subsequently, all polymorphisms were included in haplotype analyses using the PLINK software (v1. 07).


Input: After adjusting for age, height and weight, two out of five common haplotypes (MAF >= 0. 01) were found to be of particular interest in the regulation of hip and whole body BMD (AGCG, AACA).


Input: Additional analysis suggested that these latter associations are driven by the association of rs6485702.


Input: We suggest, based on these results and the localisation of the variant in the third beta-propeller domain of LRP4, that the variant has possibly a functional effect.


Input: Hereby, we conclude that common variation in the LRP4 gene determines hip and whole body BMD and thus confirm previous results from different GWAs.


Input: In addition, our data proves an additional role for LRP4 in regulating hip structure.


Input: Finally, interaction analysis for LRP4 with SOST and LRP5 showed interaction with LRP5 for femoral shaft geometry.


Input: Cardioprotective potential of N, alpha-L-rhamnopyranosyl vincosamide, an indole alkaloid, isolated from the leaves of Moringa oleifera in isoproterenol induced cardiotoxic rats: in vivo and in vitro studies.

N, alpha-L-rhamnopyranosyl vincosamide

indole alkaloid

isoproterenol


Input: Hitherto unknown protective effect of N, alpha-L-rhamnopyranosyl vincosamide (VR), isolated from Moringa oleifera leaves in isoproterenol (ISO)-induced cardiac toxicity was evaluated in rats.

N, alpha-L-rhamnopyranosyl vincosamide

isoproterenol

ISO


Input: Oral administration of VR at 40 mg/kg for 7 days markedly reduced the ISO-induced increase in the levels of serum cardiac markers such as troponin-T, creatine kinase-MB, lactate dehydrogenase and glutamate pyruvate transaminase as well as cardiac lipid peroxidation with a parallel increase in the cellular antioxidants suggesting its cardio-protective and free radical scavenging potential, which was latter confirmed by in vitro study.

ISO

creatine

lactate

glutamate pyruvate


Input: Rats treated with test compound also improved the ISO-induced abnormal changes in ECG as well as in cardiac histology.

ISO


Input: A reduction in myocardial necrosis was further evidenced by the tri-phenyl tetrazolium chloride (TTC) stain in isolated test drug pretreated rats.

tri-phenyl tetrazolium chloride

TTC


Input: These findings suggest the cardio-protective potential of the isolated alkaloid and possibly the beneficial action is mediated through its free radical scavenging property.


Input: Indenoindolone derivatives as topoisomerase II-inhibiting anticancer agents.

Indenoindolone


Input: Based on known heterocyclic topoisomerase II inhibitors and anticancer agents, various indenoindolone derivatives were predicted as potential topoisomerase II-inhibiting anticancer agents.

indenoindolone


Input: They are hydrazones, (thio) semicarbazones, and oximes of indenoindolones, and indenoindolols.

hydrazones

(thio) semicarbazones

oximes of indenoindolones

indenoindolols


Input: These derivatives with suitable substitutions exhibited potent specific inhibition of human DNA TopoII alpha while not showing inhibition of topoisomerase I and DNA intercalation, despite the fact that parent indenoindolones are known poor/moderate inhibitors of topoisomerase II.

indenoindolones


Input: The potent topoisomerase II inhibitor indenoindolone derivatives exhibited good anticancer activities compared to etoposide and 5-fluorouracil, and relatively low toxicity to normal cells.

indenoindolone

etoposide


Input: These derivatizations of indenoindolones were found to result in enhancement of anticancer activities.

indenoindolones


Input: Empirical power of very rare variants for common traits and disease: results from sanger sequencing 1998 individuals.


Input: The optimal study design for identifying rare variants associated with common disease is not yet clear and researchers have to decide whether to prioritize lower sequencing coverage on larger sample sizes, or higher coverage on smaller sample sizes.


Input: High-coverage sequencing affords several advantages, such as genotype accuracy and improved identification of very rare variants, but this comes at increased cost.


Input: However, the magnitude of the contribution of very rare variants to the statistical power of gene-based association tests is unknown.


Input: By using Sanger sequence data on seven genes from 1998 subjects with simulated phenotypes, we provide evidence that excluding very rare variants, in general, reduces the statistical power of rare variant association tests only modestly.


Input: However, if the probability of being causal and the effect size of the causal variants are inversely related to the minor allele frequency, then very rare variants do contribute to some power, however the absolute power remains low.


Input: As very rare variants constitute the majority of variants identified in sequencing studies, these findings suggest that careful attention need to be placed on the plausible relationship that exist between very rare variants and common disease. European Journal of Human Genetics advance online publication, 16 January 2013; doi: 10. 1038/ejhg. 2012. 284.


Input: The first self-sustainable microbial fuel cell stack.


Input: This study reports for the first time on the development of a self-sustainable microbial fuel cell stack capable of self-maintenance (feeding, hydration, sensing & reporting).


Input: Furthermore, the stack system is producing excess energy, which can be used for improved functionality.


Input: The self-maintenance is performed by the stack powering single and multi-channel peristaltic pumps.


Input: Activation of the alpha 7 nicotinic ACh receptor induces anxiogenic effects in rats which is blocked by a 5-HT1a receptor antagonist.


Input: The alpha 7 nicotinic acetylcholine receptor (nAChR) is highly expressed in different regions of the brain and is associated with cognitive function as well as anxiety.

acetylcholine


Input: Agonists and positive allosteric modulators (PAMs) of the alpha 7 subtype of nAChRs have been shown to improve cognition.


Input: Previously nicotine, which activates both alpha 7 and non-alpha 7 subtypes of nAChRs, has been shown to have an anxiogenic effect in behavioral tests.

nicotine


Input: In this study, we compared the effects of the alpha 7-selective agonist (PNU-282987) and PAM (PNU-120596) in a variety of behavioral tests in Sprague Dawley rats to look at their effects on learning and memory as well as anxiety.


Input: We found that neither PNU-282987 nor PNU-120596 improved spatial-learning or episodic memory by themselves.


Input: However when cognitive impairment was induced in the rats with scopolamine (1 mg/kg), both PNU-120596 and PNU-282987 were able to reverse this memory impairment and restore it back to normal levels.

scopolamine


Input: While PNU-120596 reversed the scopolamine-induced cognitive impairment, it did not have any adverse effect on anxiety.


Input: PNU-282987 on the other hand displayed an increase in anxiety-like behavior at a higher dose (10 mg/kg) that was significantly reduced by the serotonin 5-HT1a receptor antagonist WAY-100135.


Input: However the alpha 7 receptor antagonist methyllycaconitine was unable to reverse these anxiety-like effects seen with PNU-282987.

methyllycaconitine


Input: These results suggest that alpha 7 nAChR PAMs are pharmacologically advantageous over agonists, and should be considered for further development as therapeutic drugs targeting the alpha 7 receptors.


Input: Microwave absorption in powders of small conducting particles for heating applications.


Input: In microwave chemistry there is a common misconception that small, highly conducting particles heat profusely when placed in a large microwave electric field.


Input: However, this is not the case; with the simple physical explanation that the electric field (which drives the heating) within a highly conducting particle is highly screened.


Input: Instead, it is the magnetic absorption associated with induction that accounts for the large experimental heating rates observed for small metal particles.


Input: We present simple principles for the effective heating of particles in microwave fields from calculations of electric and magnetic dipole absorptions for a range of practical values of particle size and conductivity.


Input: For highly conducting particles, magnetic absorption dominates electric absorption over a wide range of particle radii, with an optimum absorption set by the ratio of mean particle radius a to the skin depth delta (specifically, by the condition a = 2. 41 delta).


Input: This means that for particles of any conductivity, optimized magnetic absorption (and hence microwave heating by magnetic induction) can be achieved by simple selection of the mean particle size.


Input: For weakly conducting samples, electric dipole absorption dominates, and is maximized when the conductivity is approximately sigma =~ 3 omega epsilon (0) =~ 0. 4 S m (-1), independent of particle radius.


Input: Therefore, although electric dipole heating can be as effective as magnetic dipole heating for a powder sample of the same volume, it is harder to obtain optimized conditions at a fixed frequency of microwave field.


Input: The absorption of sub-micron particles is ineffective in both magnetic and electric fields.


Input: However, if the particles are magnetic, with a lossy part to their complex permeability, then magnetic dipole losses are dramatically enhanced compared to their values for non-magnetic particles.


Input: An interesting application of this is the use of very small magnetic particles for the selective microwave heating of biological samples.


Input: LPA1-induced cytoskeleton reorganization drives fibrosis through CTGF-dependent fibroblast proliferation.


Input: There has been much recent interest in lysophosphatidic acid (LPA) signaling through one of its receptors, LPA1, in fibrotic diseases, but the mechanisms by which LPA-LPA1 signaling promotes pathological fibrosis remain to be fully elucidated.

lysophosphatidic acid

LPA


Input: Using a mouse peritoneal fibrosis model, we demonstrate central roles for LPA and LPA1 in fibroblast proliferation.

LPA


Input: Genetic deletion or pharmacological antagonism of LPA1 protected mice from peritoneal fibrosis, blunting the increases in peritoneal collagen by 65. 4 and 52. 9%, respectively, compared to control animals and demonstrated that peritoneal fibroblast proliferation was highly LPA1 dependent.


Input: Activation of LPA1 on mesothelial cells induced these cells to express connective tissue growth factor (CTGF), driving fibroblast proliferation in a paracrine fashion.


Input: Activation of mesothelial cell LPA1 induced CTGF expression by inducing cytoskeleton reorganization in these cells, causing nuclear translocation of myocardin-related transcription factor (MRTF)-A and MRTF-B.


Input: Pharmacological inhibition of MRTF-induced transcription also diminished CTGF expression and fibrosis in the peritoneal fibrosis model, mitigating the increase in peritoneal collagen content by 57. 9% compared to controls.


Input: LPA1-induced cytoskeleton reorganization therefore makes a previously unrecognized but critically important contribution to the profibrotic activities of LPA by driving MRTF-dependent CTGF expression, which, in turn, drives fibroblast proliferation.-Sakai, N., Chun, J., Duffield, J.


Input: S., Wada, T., Luster, A.


Input: D., Tager, A.


Input: M.


Input: LPA1-induced cytoskeleton reorganization drives fibrosis through CTGF-dependent fibroblast proliferation.


Input: Altered trace mineral milieu might play an aetiological role in the pathogenesis of polycystic ovary syndrome.


Input: Insulin resistance is a very common associate of polycystic ovary syndrome (PCOS).


Input: Pathophysiology in relation with the essential elements including copper, magnesium, zinc, manganese, chromium, and calcium has been reported in women with insulin resistance.

copper

magnesium

zinc

manganese

chromium

calcium


Input: This prospective study was designed to explore whether the women with PCOS do exhibit altered serum element levels in association with/without insulin resistance.


Input: One hundred and thirty-two women with PCOS and forty-six control women were studied.


Input: Women with PCOS were further divided based on the presence of insulin resistance (insulin resistant: n = 50; non-insulin resistant: n = 82).


Input: In all women, basal levels of gonadotropins, prolactin, testosterone, insulin, glucose, and the six different elements were measured.

testosterone

glucose


Input: Serum levels of testosterone (p < 0. 001), luteinizing hormone (p < 0. 05), and fasting insulin (p < 0. 004) were significantly higher in the PCOS population compared to controls as well as PCOS women without insulin resistance.

testosterone


Input: Women with PCOS exhibited a significantly high calcium (p < 0. 04) and lower manganese levels (p < 0. 002) when compared to controls.

calcium

manganese


Input: However, the PCOS women with insulin resistance exhibited significantly lower serum levels of magnesium and chromium (p < 0. 04), in addition to higher levels of zinc and copper (p < 0. 04).

magnesium

chromium

zinc

copper


Input: The differences in calcium (p < 0. 03) and manganese levels (p < 0. 0001) became aggravated with the presence of insulin resistance when compared to control as well as PCOS women without insulin resistance.

calcium

manganese


Input: In PCOS-associated insulin resistance, circulating serum magnesium (r =-0. 31; p < 0. 03) and chromium (r =-0. 38; p < 0. 006) status significantly correlated with fasting insulin levels.

magnesium

chromium


Input: We conclude that imbalanced element status may be a key foundation for insulin resistance in PCOS.


Input: The findings in this study should be investigated with further trials in order to obtain new insights into PCOS.


Input: Insights into TIM-barrel prenyl transferase mechanisms: crystal structures of PcrB from Bacillus subtilis and Staphylococcus aureus.


Input: Well structured: As a new triose phosphate isomerase (TIM) barrel-fold prenyl transferase, PcrB catalyzes the production of heptaprenylglyceryl phosphate from heptaprenyl diphosphate and glycerol-1-phosphate.

triose phosphate

heptaprenylglyceryl phosphate

heptaprenyl diphosphate


Input: Crystal structures of PcrB from Bacillus subtilis and Staphylococcus aureus in complex with ligands were solved, and together with site-directed mutagenesis and bioinformatics analyses, clearly reveal the catalytic mechanism of the enzyme.


Input: Cross-tolerance in amphibians: wood frog mortality when exposed to three insecticides with a common mode of action.


Input: Insecticide tolerance and cross-tolerance in nontarget organisms is often overlooked despite its potential to buffer natural systems from anthropogenic influence.


Input: We exposed wood frog tadpoles from 15 populations to three acetylcholine esterase-inhibiting insecticides and found widespread variation in insecticide tolerance and evidence for cross-tolerance to these insecticides.

acetylcholine


Input: Our results demonstrate that amphibian populations with tolerance to one pesticide may be tolerant to many other pesticides.


Input: Associations between perfluoroalkyl compounds and immune and clinical chemistry parameters in highly exposed bottlenose dolphins (Tursiops truncatus).

perfluoroalkyl


Input: Perfluoroalkyl compounds (PFCs) are ubiquitous, persistent chemical contaminants found in the environment, wildlife, and humans.

Perfluoroalkyl


Input: Despite the widespread occurrence of PFCs, little is known about the impact these contaminants have on the health of wildlife populations.


Input: The authors investigated the relationship between PFCs (including sum perfluorocarboxylates, sum perfluoroalkyl sulfonates, perfluorooctane sulfonate, perfluorooctanoic acid, and perfluorodecanoic acid) and the clinocopathologic and immune parameters in a highly exposed population (n = 79) of Atlantic bottlenose dolphins (mean sum PFCs = 1970 ng/ml; range 574-8670 ng/ml) sampled from 2003 to 2005 near Charleston, South Carolina, USA.

perfluorocarboxylates

perfluoroalkyl sulfonates

perfluorooctane sulfonate

perfluorooctanoic acid

perfluorodecanoic acid


Input: Age-adjusted linear regression models showed statistically significant positive associations between exposure to one or more of the PFC totals and/or individual analytes and the following immunological parameters: absolute numbers of CD2 + T cells, CD4 + helper T cells, CD19 + immature B cells, CD21 + mature B cells, CD2/CD21 ratio, MHCII + cells, B cell proliferation, serum IgG1, granulocytic, and monocytic phagocytosis.


Input: Several PFC analyte groups were also positively associated with serum alanine aminotransferase, gamma-glutamyltransferase, creatinine, phosphorus, amylase, and anion gap and negatively associated with cholesterol levels, creatinine phosphokinase, eosinophils, and monocytes.

alanine

creatinine

phosphorus

cholesterol

creatinine


Input: Based on these relationships, the authors suggest that the PFC concentrations found in Charleston dolphins may have effects on immune, hematopoietic, kidney, and liver function.


Input: The results contribute to the emerging data on PFC health effects in this first study to describe associations between PFCs and health parameters in dolphins.


Input: Potential for metal contamination by direct sonication of nanoparticle suspensions.


Input: While conducting toxicity tests with nano titanium dioxide, the authors found that test suspensions were being contaminated with aluminum and titanium from tip erosion during direct sonication.

titanium dioxide

aluminum

titanium


Input: The contaminating alloy particles had a measurable size distribution and zeta potential using dynamic light scattering, which changed the measured characteristics of the suspensions.


Input: Caution should be used when employing direct sonication for preparing test suspensions due to potential interferences of these particles in toxicological assessments.


Input: Korean guidelines for pharmacoeconomic evaluation (second and updated version): consensus and compromise.


Input: The first version of the Korean guidelines for pharmacoeconomic evaluation was published by Health Insurance Review and Assessment Service (HIRA) in 2006.


Input: Since the introduction of the first version, domestic experience with the application of the recommendations has accumulated, and methodologies in certain areas have progressed considerably.


Input: Based on these experiences, HIRA initiated a guidelines revision project to address the need for revisions.


Input: The purpose of this study is to share the process used to complete these guideline revisions and to provide the contents of the revised guidelines.


Input: In developing the current revision, meetings with the advisory committee and working-level meetings with pharmaceutical companies were held several times to reach as much of a consensus as possible, and the results of a survey of pharmaceutical companies and decision makers regarding the existing guidelines were considered.


Input: The second version of the guidelines clarified the level of data requirement (' must',' recommended',' preferred') based on the data availability, the information needs of the decision makers and the strength of the evidence.


Input: The recommended perspective economic studies should take has been modified and additional guidance has been provided on QALY measurement.


Input: Manuals for systematic reviews and indirect comparisons have been published, and a standardized reporting format for expert opinions has been added.


Input: Sections on preferred methods for evaluations, sensitivity analysis, modelling and time horizon have been elucidated.


Input: The revised guidelines clarify the expression of the recommendations, making them more user-friendly, and provide more specific guidance to improve the quality and comparability across submissions.


Input: Heterocycles as nonclassical bioisosteres of alpha-amino acids.

alpha-amino acids


Input: Bioisosterism of alpha-amino acids is often accomplished by replacing the alpha-carboxylate with one of the many known carboxylic acid bioisosteres.

alpha-amino acids

alpha-carboxylate

carboxylic acid


Input: However, bioisosterism of the whole alpha-amino acid moiety is accomplished with heterocyclic bioisosteres that often display an acidic function.

alpha-amino acid


Input: In this Minireview, we summarized the reported heterocycles as nonclassical bioisosteres of alpha-amino acids, which include quinoxaline-2, 4 (1H)-dione, quinoxaline-2, 3 (1H)-dione and quinolin-2 (1H)-one, azagrevellin and azepine-derived structures.

alpha-amino acids

quinoxaline-2, 4 (1H)-dione

quinoxaline-2, 3 (1H)-dione

quinolin-2 (1H)-one

azagrevellin

azepine


Input: The binding mode of the crystalized bioisosteres were compared with those of the crystalized alpha-amino acids that bind in the same domain, and where no data on the crystal structure were available, the displacement studies of known orthosteric ligands were used.

alpha-amino acids


Input: The reported bioisosteres share the following essential structural features for mimicking alpha-amino acids: an aromatic ring system joined to a lactam ring system with an acidic feature next to the lactam carbonyl, where this acidic feature together with the lactam carbonyl can mimic the alpha-carboxylate, and the lactam nitrogen together with the aromatic ring system can mimic the alpha-ammonium.

alpha-amino acids

lactam carbonyl

lactam carbonyl

alpha-ammonium


Input: The majority of these heterocycles can be prepared from three common corresponding starting materials: the corresponding anilines, isatins or anthranilic esters.

anilines

isatins

anthranilic esters


Input: The data collected here show the potential of this class of bioisosteres in the design of glutamate receptor ligands and beyond.

glutamate


Input: Effects of antiresorptive therapies on glucose metabolism: Results from the FIT, HORIZON-PFT and FREEDOM trials.

glucose


Input: In rodent models undercarboxylated osteocalcin (ucOC) acts as a hormone promoting insulin sensitivity and secretion.


Input: If ucOC plays a similar role in humans, then antiresorptive therapies, which reduce ucOC levels, may increase the risk of insulin resistance and diabetes.


Input: We tested whether antiresorptive therapies result in higher fasting glucose, increased weight, or greater diabetes incidence in post-hoc analyses of three randomized, placebo-controlled trials in postmenopausal women: Fracture Intervention Trial (FIT) (N = 6151) of alendronate (4 years), Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly Pivotal Fracture Trial (HORIZON-PFT) (N = 7113) of zoledronic acid (3 years), and Fracture REduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) trial (N = 7076) of denosumab (3 years).

glucose

alendronate

Zoledronic Acid

zoledronic acid


Input: Fasting glucose was measured annually in FIT and HORIZON in a subset of women, and every 6 months in FREEDOM on all participants.

glucose


Input: Weight was measured annually in all trials.


Input: Incident diabetes was identified from adverse event reports, initiation of diabetes medication, or elevated fasting glucose.

glucose


Input: Differences in fasting glucose changes from randomization to trial conclusion between treatment and placebo groups were not statistically significant:-0. 47 mg/dL in FIT, 0. 20 mg/dL in HORIZON-PFT and 0. 09 mg/dL in FREEDOM, all p > 0. 6.

glucose


Input: Weight change differed between treatment and placebo groups in FIT (0. 32 kg, p = 0. 003) and FREEDOM (0. 31 kg, p = 0. 023), but not in HORIZON-PFT (0. 15 kg, p = 0. 132).


Input: In the three trials combined, diabetes occurred in 203 and 225 women assigned to treatment or placebo, respectively.


Input: Diabetes incidence was not increased in any of the treatment groups or in the pooled estimate (Pooled RR = 0. 90; 95% CI 0. 74, 1. 10).


Input: Antiresorptive therapy does not have a clinically important effect on fasting glucose, weight or diabetes risk in postmenopausal women.

glucose


Input: Contrary to predictions from mouse models, reduced bone turnover does not appear to play a significant role in glucose metabolism in humans.

glucose


Input: (c) 2013 American Society for Bone and Mineral Research.


Input: Single-walled carbon nanotube/polyaniline/n-silicon solar cells: fabrication, characterization, and performance measurements.

carbon

polyaniline

silicon


Input: Carbon nanotube-silicon solar cells are a recently investigated photovoltaic architecture with demonstrated high efficiencies.

Carbon

silicon


Input: Silicon solar-cell devices fabricated with a thin film of conductive polymer (polyaniline) have been reported, but these devices can suffer from poor performance due to the limited lateral current-carrying capacity of thin polymer films.

Silicon

polyaniline


Input: Herein, hybrid solar-cell devices of a thin film of polyaniline deposited on silicon and covered by a single-walled carbon nanotube film are fabricated and characterized.

polyaniline

silicon

carbon


Input: These hybrid devices combine the conformal coverage given by the polymer and the excellent electrical properties of single-walled carbon nanotube films and significantly outperform either of their component counterparts.

carbon


Input: Treatment of the silicon base and carbon nanotubes with hydrofluoric acid and a strong oxidizer (thionyl chloride) leads to a significant improvement in performance.

silicon

carbon

hydrofluoric acid

thionyl chloride


Input: The regulation of Runx2 by FGF2 and connexin43 requires the inositol polyphosphate/protein kinase C delta cascade.

inositol polyphosphate


Input: Connexin43 (Cx43) plays a critical role in osteoblast function and bone mass accrual, yet the identity of the second messengers communicated by Cx43 gap junctions, the targets of these second messengers and how they regulate osteoblast function remain largely unknown.


Input: We have shown that alterations of Cx43 expression in osteoblasts can impact the responsiveness to fibroblast growth factor-2 (FGF2), by modulating the transcriptional activity of Runx2.


Input: In this study, we examined the contribution of the phospholipase C gamma 1/inositol polyphosphate/PKC delta cascade to the Cx43-dependent transcriptional response of MC3T3 osteoblasts to FGF2.

inositol polyphosphate


Input: Knockdown of expression and/or inhibition of function of phospholipase C gamma 1, inositol polyphosphate multikinase, which generates InsP (4) and InsP (5), and inositol hexakisphosphate kinase 1/2, which generates inositol pyrophosphates, prevented the ability of Cx43 to potentiate FGF2-induced signaling through Runx2.

inositol polyphosphate

inositol hexakisphosphate

inositol pyrophosphates


Input: Conversely, overexpression of phospholipase C gamma 1 and inositol hexakisphosphate kinase 1/2 enhanced FGF2 activation of Runx2 and the effect of Cx43 overexpression on this response.

inositol hexakisphosphate


Input: Disruption of these pathways blocked the nuclear accumulation of PKC delta and the FGF2-dependent interaction of PKC delta and Runx2, reducing Runx2 transcriptional activity.


Input: These data reveal that FGF2-signaling involves the inositol polyphosphate cascade, including IP6K, and demonstrate that IP6K regulates Runx2 and osteoblast gene expression.

inositol polyphosphate


Input: Additionally, these data implicate the water-soluble inositol polyphosphates as mediators of the Cx43-dependent amplification of the osteoblast response to FGF2, and suggest that these low molecular weight second messengers may be biologically relevant mediators of osteoblast function that are communicated by Cx43-gap junctions.

inositol polyphosphates


Input: (c) 2013 American Society for Bone and Mineral Research.


Input: Betaglycan alters NF kappa B-TGF beta 2 cross talk to reduce survival of human granulosa tumor cells.


Input: The molecular pathways controlling granulosa cell tumor (GCT) survival are poorly understood.


Input: In many cell types, nuclear factor-kappa B (NF kappa B) and TGF beta coordinately regulate cell survival to maintain tissue homeostasis.


Input: Because GCT cell lines exhibit constitutively activated NF kappa B, we hypothesized that NF kappa B blocks TGF beta-mediated cell death in GCT cells.


Input: To test this hypothesis, we used the human GCT cell line KGN, which exhibits loss of betaglycan, a TGF beta co-receptor.


Input: After inhibition of NF kappa B in KGN cells, re-expression of betaglycan resulted in a decrease in cell viability, which was further decreased by TGF beta 2.


Input: Intriguingly, TGF beta 2 increased NF kappa B reporter activity in control cells, but betaglycan expression suppressed both basal and TGF beta 2-stimulated NF kappa B activity.


Input: Chemical inhibition of Mothers against decapentaplegic homolog 2/3 (SMAD2/3) signaling or SMAD2/3 gene silencing revealed that both SMADs contributed to cell survival.


Input: Furthermore, inhibiting NF kappa B activity resulted in a specific reduction in SMAD3 expression.


Input: Conversely, overexpression of SMAD3 increased basal NF kappa B activity and countered betaglycan-mediated suppression of NF kappa B activity.


Input: Finally, ERK1/2 activation emerged as the point of convergence of NF kappa B, SMAD3, and TGF beta 2/betaglycan governance of GCT cell viability.


Input: Key findings in KGN cells were reproduced in a second GCT cell line, COV434.


Input: Collectively, our data establish that both SMAD2/3 and NF kappa B signaling pathways support GCT cell viability and suggest the existence of a positive feedback loop between NF kappa B and SMAD3 signaling in late-stage GCT.


Input: Furthermore, our data suggest that loss of betaglycan during tumor progression in GCT alters the functional outcomes generated by NF kappa B and TGF beta pathway cross talk.


Input: Genome-wide screen for modulation of hepatic apolipoprotein A-I (ApoA-I) secretion.


Input: Control of plasma cholesterol levels is a major therapeutic strategy for management of coronary artery disease (CAD).

cholesterol


Input: Although reducing LDL cholesterol (LDL-c) levels decreases morbidity and mortality, this therapeutic intervention only translates into a 25-40% reduction in cardiovascular events.

cholesterol


Input: Epidemiological studies have shown that a high LDL-c level is not the only risk factor for CAD; low HDL cholesterol (HDL-c) is an independent risk factor for CAD.

cholesterol


Input: Apolipoprotein A-I (ApoA-I) is the major protein component of HDL-c that mediates reverse cholesterol transport from tissues to the liver for excretion.

cholesterol


Input: Therefore, increasing ApoA-I levels is an attractive strategy for HDL-c elevation.


Input: Using genome-wide siRNA screening, targets that regulate hepatocyte ApoA-I secretion were identified through transfection of 21, 789 siRNAs into hepatocytes whereby cell supernatants were assayed for ApoA-I.


Input: Approximately 800 genes were identified and triaged using a convergence of information, including genetic associations with HDL-c levels, tissue-specific gene expression, druggability assessments, and pathway analysis.


Input: Fifty-nine genes were selected for reconfirmation; 40 genes were confirmed.


Input: Here we describe the siRNA screening strategy, assay implementation and validation, data triaging, and example genes of interest.


Input: The genes of interest include known and novel genes encoding secreted enzymes, proteases, G-protein-coupled receptors, metabolic enzymes, ion transporters, and proteins of unknown function.


Input: Repression of farnesyltransferase (FNTA) by siRNA and the enzyme inhibitor manumycin A caused elevation of ApoA-I secretion from hepatocytes and from transgenic mice expressing hApoA-I and cholesterol ester transfer protein transgenes.

manumycin A

cholesterol ester


Input: In total, this work underscores the power of functional genetic assessment to identify new therapeutic targets.


Input: Self-assembly of ordered epitaxial nanostructures on polygonal nanowires.


Input: We study the self-assembly of ordered nanostructures, that is, nanorings (NRs) and quantum dots (QDs), epitaxially grown on a polygonal cross-section nanowire (PCS-NW) using both theoretical and phase-field modeling.


Input: Our studies show that, by increasing the PCS-NW size, transitions from ordered NRs to ordered QDs on facets and further to ordered QDs on ridges occur.


Input: The predicted morphologies and their transitions are in excellent agreement with existing experiments.


Input: Our study suggests a novel approach to fabricate ordered nanostructures on nanowires.


Input: Optimization of Non-ATP Competitive CDK/Cyclin Groove Inhibitors through REPLACE-Mediated Fragment Assembly.

ATP


Input: A major challenge in drug discovery is to develop and improve methods for targeting protein-protein interactions.


Input: Further exemplification of the REPLACE (REplacement with Partial Ligand Alternatives through Computational Enrichment) strategy for generating inhibitors of protein-protein interactions demonstrated that it can be used to optimize fragment alternatives of key determinants, to combine these in an effective way, and this was achieved for compounds targeting the cyclin-dependent kinase 2 (CDK2) substrate recruitment site on the cyclin regulatory subunit.


Input: Phenylheterocyclic isosteres replacing a critical charge-charge interaction provided new structural insights for binding to the cyclin groove.


Input: In particular, these results shed light onto the key contributions of a H-bond observed in crystal structures of N-terminally capped peptides.

H

N


Input: Furthermore, the structure-activity relationship of a bis (aryl) ether C-terminal capping group mimicking dipeptide interactions was probed through ring substitutions, allowing increased complementarity with the primary hydrophobic pocket.

bis (aryl) ether C

dipeptide


Input: This study further validates REPLACE as an effective strategy for converting peptidic compounds to more pharmaceutically relevant compounds.


Input: The volume of distribution is an indicator of poor in vitro-in vivo extrapolation of clearance for acidic drugs in the rat.


Input: Abstract 1.


Input: We applied the regression offset approach to predict rat in vivo intrinsic clearance (CLint) for 54 new chemical acid entities with high plasma protein binding values and low renal clearance (CL).


Input: The prediction success was correlated to volume of distribution (Vd), molecular weight (Mw) and CL.


Input: A correlation between poor in vitro-in vivo extrapolation (IVIVE) and Vd values distinct from the Vd of albumin (0. 1-0. 2 L/kg) was revealed.


Input: For compounds with a Vd value above 0. 5 L/kg, 0% of the predictions of in vivo CLint was within twofold of the observed value, compared to 69% for compounds with a Vd value below 0. 5 L/kg.


Input: 3. Compounds with a Mw below 450 g/mol demonstrated more accurate in vivo CLint predictions than compounds with a Mw above 450 g/mol, i. e. 63% compared to 21% within twofold.


Input: For compounds with in vivo CL below 30% of the liver blood flow (LBF), 53% of the predictions was within twofold of the observed value, compared to 0% for compounds with CL above 30% of the LBF.


Input: We show that accurate IVIVE for acidic compounds with high plasma protein binding and low renal CL can be associated with a low Vd (i. e. around the Vd of albumin) and with a low in vivo CL, and that Mw is an important optimization parameter for pharmacokinetic.


Input: This study also further demonstrates the advantages of the application of the regression method for identifying cases when metabolic CL is not the single major elimination pathway.


Input: Four new koumine metabolites in rat liver microsomes.

koumine


Input: Four new metabolites M-1 [1, 2, 18, 19-tetradehydro-4-demethyl-3, 17-epoxy-7, 20 (2H, 19H)-cyclovobasan], M-2 [1, 2, 4, 21, 18, 19-hexadehydro-4-demethyl-3, 17-epoxy-7, 20 (2H, 19H)-cyclovobasan], M-3 [1, 2, 18, 19-tetradehydro-4-demethyl-4-formaldehyde-3, 17-epoxy-7, 20 (2H, 19H)-cyclovobasan], and M-4 [1, 2, 4, 21, 18, 19-hexadehydro-4-demethyl-4-oxy-3, 17-epoxy-7, 20 (2H, 19H)-cyclovobasan] were isolated from the chloroform extract of koumine incubated with phenobarbital-treated rat liver microsomes.

1, 2, 18, 19-tetradehydro-4-demethyl-3, 17-epoxy-7, 20 (2H, 19H)-cyclovobasan

1, 2, 4, 21, 18, 19-hexadehydro-4-demethyl-3, 17-epoxy-7, 20 (2H, 19H)-cyclovobasan

1, 2, 18, 19-tetradehydro-4-demethyl-4-formaldehyde-3, 17-epoxy-7, 20 (2H, 19H)-cyclovobasan

1, 2, 4, 21, 18, 19-hexadehydro-4-demethyl-4-oxy-3, 17-epoxy-7, 20 (2H, 19H)-cyclovobasan

chloroform

koumine

phenobarbital


Input: The structures of M-1, M-2, M-3, and M-4 were elucidated by spectroscopic methods including ESI-TOF-MS, 1D, and 2D NMR experiments.


Input: The metabolic pathway of koumine was proposed.

koumine


Input: The cytotoxic activities between koumine and its metabolites were also compared in the A549 cell line.

koumine


Input: Polymorphism of GeSbTe superlattice nanowires.

GeSbTe


Input: Scaling-down of phase change materials to a nanowire (NW) geometry is critical to a fast switching speed of nonvolatile memory devices.


Input: Herein, we report novel composition-phase-tuned GeSbTe NWs, synthesized by a chemical vapor transport method, which guarantees promising applications in the field of nanoscale electric devices.

GeSbTe


Input: As the Sb content increased, they showed a distinctive rhombohedral-cubic-rhombohedral phase evolution.

Sb


Input: Remarkable superlattice structures were identified for the Ge (8) Sb (2) Te (11), Ge (3) Sb (2) Te (6), Ge (3) Sb (8) Te (6), and Ge (2) Sb (7) Te (4) NWs.

Ge (8) Sb (2) Te (11)

Ge (3) Sb (2) Te (6)

Ge (3) Sb (8) Te (6)

Ge (2) Sb (7) Te (4)


Input: The coexisting cubic-rhombohedral phase Ge (3) Sb (2) Te (6) NWs exhibited an exclusively uniform superlattice structure consisting of 2. 2 nm period slabs.

Ge (3) Sb (2) Te (6)


Input: The rhombohedral phase Ge (3) Sb (8) Te (6) and Ge (2) Sb (7) Te (4) NWs adopted an innovative structure; 3Sb (2) layers intercalated the Ge (3) Sb (2) Te (6) and Ge (2) Sb (1) Te (4) domains, respectively, producing 3. 4 and 2. 7 nm period slabs.

Ge (3) Sb (8) Te (6)

Ge (2) Sb (7) Te (4)

3Sb (2)

Ge (3) Sb (2) Te (6)

Ge (2) Sb (1) Te (4)


Input: The current-voltage measurement of the individual NW revealed that the vacancy layers of Ge (8) Sb (2) Te (11) and Ge (3) Sb (2) Te (6) decreased the electrical conductivity.

Ge (8) Sb (2) Te (11)

Ge (3) Sb (2) Te (6)


Input: A new flavonoid with 6-phenyl substituent from Selaginella uncinata.

flavonoid


Input: A new flavonoid, 6-(5-acetyl-2-methoxyphenyl)-apigenin (1), together with nine known compounds (2-10), was isolated from Selaginella uncinata (Desv.) Spring.

flavonoid


Input: This is the first report of the spectroscopic data of compound 3.


Input: Compound 2 was first reported from this species.


Input: The structure of the new compound was elucidated on the basis of spectroscopic evidence, including 1D and 2D NMR as well as HR-EI-MS analysis.


Input: Controlled assembly and release of retinoic acid based on the layer-by-layer method.

retinoic acid


Input: All-trans retinoic acid (RA) has been proved to play important roles in regulating cell growth in various types of cells.

All-trans retinoic acid


Input: Yet most experiments were performed by adding RA in solution previously.


Input: In this Article, we focus on the incorporation of RA, as a negatively charged moiety, into layered polyelectrolyte films on surfaces by means of layer-by-layer (LbL) deposition, followed by adding of capping layers to regulate the release of RA from the films.


Input: The incorporated RA was designed to release over 5 days in buffer solution.


Input: The assembly and release of RA were verified by UV and QCM results.


Input: The controlled release of RA from multilayer films can serve as a model system to study the influence of small molecules on cell growth.


Input: Phase separation induced by Au catalysts in ternary InGaAs nanowires.

Au

InGaAs


Input: We report a novel phase separation phenomenon observed in the growth of ternary In (x) Ga (1-x) As nanowires by metalorganic chemical vapor deposition.

In (x) Ga (1-x) As


Input: A spontaneous formation of core-shell nanowires is investigated by cross-sectional transmission electron microscopy, revealing the compositional complexity within the ternary nanowires.


Input: It has been found that for In (x) Ga (1-x) As nanowires high precursor flow rates generate ternary In (x) Ga (1-x) As cores with In-rich shells, while low precursor flow rates produce binary GaAs cores with ternary In (x) Ga (1-x) As shells.

In (x) Ga (1-x) As

In (x) Ga (1-x) As

GaAs

In (x) Ga (1-x) As


Input: First-principle calculations combined with thermodynamic considerations suggest that this phenomenon is due to competitive alloying of different group-III elements with Au catalysts, and variations in elemental concentrations of group-III materials in the catalyst under different precursor flow rates.

Au


Input: This study shows that precursor flow rates are critical factors for manipulating Au catalysts to produce nanowires of desired composition.

Au


Input: Synthesis and antibacterial evaluation of typharin analog: 6, 8-dihydroxy-7-methyl-3-styryl-3, 4-dihydroisocoumarin.

typharin

6, 8-dihydroxy-7-methyl-3-styryl-3, 4-dihydroisocoumarin


Input: Synthesis of the 6-hydroxy-7-methyl analog of typharin (8-dihydroxy-3-styryl-3, 4-dihydroisocoumarin) isolated from the rhizomes of Typha capensis has been described.

typharin

8-dihydroxy-3-styryl-3, 4-dihydroisocoumarin


Input: Direct condensation of 3, 5-dimethoxy-4-methylhomophthalic acid (1) with cinnamoyl chloride at elevated temperature under inert conditions afforded 6, 8-dihydroxy-7-methyl-3-styrylisocoumarin (2).

3, 5-dimethoxy-4-methylhomophthalic acid

cinnamoyl chloride

6, 8-dihydroxy-7-methyl-3-styrylisocoumarin


Input: Hydrolysis of isocoumarin to keto acid (3) followed by reduction and cyclodehydration of hydroxy acid analog (4) afforded (+/-)-6, 8-dimethoxy-3-(4-methoxyphenyl)-3, 4-dihydroisocoumarin (5).

isocoumarin

keto acid

hydroxy acid

(+/-)-6, 8-dimethoxy-3-(4-methoxyphenyl)-3, 4-dihydroisocoumarin


Input: Demethylation of the latter using anhydrous aluminum chloride/ethane thiol furnished the title isocoumarin (6).

aluminum chloride

ethane thiol

isocoumarin


Input: Compounds (1-6) were screened for in vitro antibacterial activity against a representative panel of Gram-positive and Gram-negative bacteria using levofloxacin as the reference drug.

levofloxacin


Input: Successful factorial design for the optimization of methylprednisolone encapsulation in biodegradable nanoparticles.

methylprednisolone


Input: Due to their crystalline nature, the encapsulation of hydrophobic corticosteroids within polymeric nanoparticles by o/w solvent evaporation method is often difficult to achieve.

corticosteroids


Input: The aim of this study was to evaluate the effect of both process and formulation parameters on the encapsulation of a model corticosteroid: methylprednisolone (MP).

corticosteroid

methylprednisolone


Input: For this purpose, a 3 (2) factorial design was performed evaluating the effects of the concentration of emulsifiers and sonication time on the manufactured nanoparticles, followed by a multiresponse optimization.


Input: The study also included the evaluation of other parameters such as the type of organic solvent used, polymer characteristics and the initial mass of drug.


Input: The optimal nanoparticle formulation using 0. 25% (w/v) of emulsifying agent (Polyvinyl-alcohol, PVA) and 5 min of sonication was then characterized.

Polyvinyl-alcohol

PVA


Input: The highest encapsulation was obtained with an organic phase consisting of acetone: dichloromethane (1: 1), polyD, L-lactide-co-glycolide (PLGA) 50: 50 as polymer and an initial mass of 6. 6 mg of methylprednisolone.

acetone

dichloromethane

polyD, L-lactide-co-glycolide

PLGA

methylprednisolone


Input: Nanoparticles size and zeta potential of optimized formulation were respectively around 230 nm and-14 mV.


Input: Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) demonstrated that the drug was molecularly dispersed within the nanoparticles.


Input: Release study showed that MP-loaded nanoparticles sustained drug release for up to 120 h.


Input: This study reflects the importance of factorial design to optimize the manufacture of nanoparticles encapsulating hydrophobic drugs.


Input: Fasciospyrinadine, a novel sesquiterpene pyridine alkaloid from a Guangxi sponge Fasciospongia sp.

Fasciospyrinadine

sesquiterpene pyridine alkaloid


Input: Fasciospyrinadine (1), a novel sesquiterpene pyridine alkaloid with a previously unreported skeleton featuring a monocyclicfarnesane moiety attached to a 3-methylenepyridine residue, was isolated from the sponge Fasciospongia sp. from Weizhou Island, Guangxi Autonomous Region.

Fasciospyrinadine

sesquiterpene pyridine alkaloid

monocyclicfarnesane


Input: The structure and the relative stereochemistry of 1 were elucidated on the basis of extensive analysis of its 1D and 2D NMR spectroscopic techniques.


Input: Fundamental and Torsional Combination Bands of Two Isomers of the OCS-CO (2) Complex in the CO (2) nu (3) Region.

OCS

CO (2)

CO (2)


Input: Spectra of two isomers of the weakly bound complex OCS-CO (2) are observed in the region of the CO (2) nu (3) fundamental vibration (~ 2349 cm (-1)), using an infrared tunable diode laser to probe a pulsed supersonic slit-jet expansion.

OCS

CO (2)

CO (2)


Input: Two bands are measured and analyzed for each isomer, the fundamental asymmetric stretch of the CO (2) component and a combination band involving this fundamental plus the intermolecular out-of-plane torsional mode.

CO (2)


Input: For one isomer, the corresponding torsional combination band is also detected in the OCS nu (1) stretching region (~ 2060 cm (-1)).

OCS


Input: The resulting torsional frequencies are found to be 18. 8 and 15. 9 cm (-1) for isomers a and b of OCS-CO (2), respectively.

OCS

CO (2)


Input: This may be the first time that such a combination band is observed for a higher-energy isomer of a weakly bound complex.


Input: The resolution of aglinin A epimers and their NMR assignments.

aglinin A


Input: Aglinin A (1) is a mixture of C (24)-epimeric 20S, 24-epoxy-24, 25-dihydroxy-3, 4-secodammar-4 (28)-en-3-oic acid and present in plants of the family Meliaceae.

Aglinin A

20S, 24-epoxy-24, 25-dihydroxy-3, 4-secodammar-4 (28)-en-3-oic acid


Input: The two epimers of 1 were resolved through an acetonide reaction, and the absolute configurations of two derivatives were deduced by the analysis of their (13) C NMR differences induced by gamma-gauche or steric effect.

acetonide

(13) C


Input: Based on it, the (13) C NMR assignment of 24R-1 and 24S-1 was also established.

(13) C


Input: Phthalazinone inhibitors of inosine-5'-monophosphate dehydrogenase from Cryptosporidium parvum.

Phthalazinone


Input: Cryptosporidium parvum (Cp) is a potential biowarfare agent and major cause of diarrhea and malnutrition.


Input: This protozoan parasite relies on inosine 5'-monophosphate dehydrogenase (IMPDH) for the production of guanine nucleotides.

inosine 5'-monophosphate

guanine nucleotides


Input: A CpIMPDH-selective N-aryl-3, 4-dihydro-3-methyl-4-oxo-1-phthalazineacetamide inhibitor was previously identified in a high throughput screening campaign.

N-aryl-3, 4-dihydro-3-methyl-4-oxo-1-phthalazineacetamide


Input: Herein we report a structure-activity relationship study for the phthalazinone-based series that resulted in the discovery of benzofuranamide analogs that exhibit low nanomolar inhibition of CpIMPDH.

phthalazinone

benzofuranamide


Input: In addition, the antiparasitic activity of select analogs in a Toxoplasma gondii model of C. parvum infection is also presented.


Input: Dietary composition of carbohydrates contributes to the development of experimental type 2 diabetes.

carbohydrates


Input: Evidence has emerged supporting a link between high glycaemic index (GI) diets and type 2 diabetes (T2D).


Input: The aim of this study was to determine if dietary GI influences the development of hyperglycaemia in C57BL/6 mice to more closely reflect T2D.


Input: Male C57BL/6 mice (n = 30) were randomly divided into 3 dietary groups consisting of either standard rodent chow (4. 8% fat, 20% protein), or a high fat (HF) diet (21-23% fat, 19% protein) with low GI (15. 4% starch; HF-LG) or high GI (50. 5% dextrose; HF-HG) ad libitum for 10 weeks.

dextrose


Input: Body weight, blood glucose, glucose tolerance, and circulating cholesterol and triglyceride levels were measured for the duration of the study.

glucose

glucose

cholesterol

triglyceride


Input: We found that increasing the GI of a moderately HF diet induces severe hyperglycaemia and insulin resistance in C57BL/6 mice, reflective of criteria for diagnosis of T2D, whilst littermates consuming an equivalent low GI diet maintain glucose homeostasis.

glucose


Input: This study demonstrates the significant contribution of both dietary carbohydrate and fat composition in the aetiopathogenesis of T2D.

carbohydrate


Input: The high harm score of alcohol.

alcohol


Input: Time for drug policy to be revisited?


Input: The aim of this paper is to create awareness of the negative health impact and economic burden and benefits associated to alcohol consumption.

alcohol


Input: Worldwide about two billion people consume alcohol.

alcohol


Input: Low intake of alcohol has a minor protective cardiovascular effect.

alcohol


Input: On the other hand, even moderate alcohol consumption appears to be weakly, but significantly, associated to a limited number of chronic diseases.

alcohol


Input: Alcohol causes a considerable economic burden to society due to the high absolute number of alcohol consumers.

Alcohol

alcohol


Input: As such, alcohol abuse is more harmful for public health and society than illicit drug use.

alcohol


Input: Some 3. 7% of alcohol consumers (worldwide 76 million people) have an alcohol use disorder leading to 60-70% of the societal costs related to alcohol.

alcohol

alcohol

alcohol


Input: Therefore, policy measures should, in addition to regulatory measures to reduce alcohol use, aim at closing the treatment gap and improving treatment effectiveness of people with an alcohol use disorder.

alcohol

alcohol


Input: The key message is that policy-makers unjustifiably focus on the harm of illicit drugs, whereas they underestimate the harm of alcohol use.

alcohol


Input: Policy makers should therefore consider alcohol to be at least as harmful as illicit drugs and invest more in prevention and harm reduction strategies for alcohol abuse and dependence.

alcohol

alcohol


Input: Adjunctive aripiprazole therapy with escitalopram in patients with co-morbid major depressive disorder and alcohol dependence: clinical and neuroimaging evidence.

aripiprazole

escitalopram

alcohol


Input: The effective treatment of depression has been reported to reduce the severity of alcohol use, potentially reflecting improvements in common brain reward circuits.

alcohol


Input: We hypothesized that augmentation therapy of escitalopram with aripiprazole would improve depressive symptoms as well as reduce craving for alcohol and cue-induced brain activity in patients with co-morbid alcohol dependence and major depressive disorder, compared with treatment with escitalopram alone.

escitalopram

aripiprazole

alcohol

alcohol

escitalopram


Input: Thirty-five subjects with major depressive disorder and alcohol dependence were recruited and randomly assigned into 17 aripiprazole + escitalopram and 18 escitalopram only groups.

alcohol

aripiprazole

escitalopram

escitalopram


Input: At baseline and following six weeks of treatment, symptoms of depression, craving for alcohol and brain activity were evaluated.

alcohol


Input: During the six week treatment period, Beck Depression Inventory and clinical global index-severity (CGI-S) scores decreased in both the aripiprazole + escitalopram and escitalopram only groups.

aripiprazole

escitalopram

escitalopram


Input: In addition, following the treatment period, the Korean alcohol urge questionnaire scores in the aripiprazole + escitalopram group were reduced from 23. 3 +/- 8. 4 to 14. 3 +/- 4. 9, compared with those of the escitalopram group of from 21. 6 +/- 8. 4 to 19. 3 +/- 7. 1 (F = 13. 1, p < 0. 01).

alcohol

aripiprazole

escitalopram

escitalopram


Input: The activity within the anterior cingulate was increased in response to the presentation of alcohol drinking scenes following treatment in the aripiprazole + escitalopram group.

alcohol

aripiprazole

escitalopram


Input: The change of brain activity within the left anterior cingulate gyrus in all patients with co-morbid alcohol dependence and major depressive disorder was negatively correlated with the change in craving for alcohol.

alcohol

alcohol


Input: These findings suggest that the effects of aripiprazole on anterior cingulate cortex might mediate the successful treatment of alcohol dependence in patients with major depressive disorder.

aripiprazole

alcohol


Input: A functional NPSR1 gene variant and environment shape personality and impulsive action: A longitudinal study.


Input: Neuropeptide S and its receptor NPSR1 are involved in the regulation of arousal, attention and anxiety.


Input: We examined whether the NPSR1 gene functional polymorphism Asn (107) Ile (rs324981, A > T) influences personality, impulsivity, and attention-deficit/hyperactivity disorder (ADHD)-related symptoms in a population-representative sample, and whether any eventual associations depend on age, sex, family relations and stressful life events (SLE).


Input: We used self-reports or teachers' ratings for both the younger (n = 593) and older (n = 583) cohort of the longitudinal Estonian Children Personality, Behaviour and Health Study.


Input: Males with the TT genotype displayed more ADHD-related symptoms.


Input: Adaptive impulsivity and Extraversion increased the most from age 18 to 25.


Input: While highest increases were observed in AA men, TT women exhibited the largest decreases.


Input: For participants with the AA genotype, Warmth in family was inversely associated with Neuroticism, and positively associated with Extraversion and Adaptive impulsivity.


Input: High exposure to SLE increased impulsivity and ADHD scores in TT genotype subjects.


Input: We conclude that the NPSR1 A/T polymorphism is associated with impulsivity, ADHD symptoms and personality, mirroring the activity-and anxiety-mediating role of NPSR1.


Input: Heterozygous individuals were the least sensitive to environmental factors, whereas subjects with the AA genotype and TT genotype reacted to different types of environmental adversities.


Input: Losmapimod concentration-QT relationship in healthy volunteers: meta-analysis of data from six clinical trials.

Losmapimod


Input: PURPOSE: The objective of this work was to describe the losmapimod concentration-QT relationship using meta-analysis of data from clinical trials with healthy volunteers and to evaluate the covariates that have significant impact on the QT prolongation.

losmapimod


Input: METHODS: Losmapimod plasma concentration and QT interval data were collected from six early clinical studies with healthy volunteers.

Losmapimod


Input: The electrocardiograms (ECGs) were collected at baseline and at a number of post-dose time points (losmapimod or placebo).

losmapimod


Input: The population pharmacokinetic/pharmacodynamic (PK/PD) modelling approach was applied to investigate the relationship between losmapimod concentration and QT prolongation.

losmapimod


Input: RESULTS: The dataset for analysis comprised 190 healthy adults who took at least one dose of losmapimod or placebo.

losmapimod


Input: Of the 2, 494 QT observations collected, 1, 532 observations had matched QT and losmapimod plasma concentration data.

losmapimod


Input: Population PK/PD analyses indicated that the model with the individual heart rate correction factor (alpha) fitted the data better than those using fixed alpha (0. 33 for Fridericia' s correction or 0. 5 for Bazett' s correction) and that there was no relationship between losmapimod concentration and QT interval.

losmapimod


Input: Female volunteers had about a 3% higher QT interval at baseline than the male volunteers.


Input: No other covariates had a significant effect on the QT interval.


Input: CONCLUSIONS: It is appropriate to apply population PK/PD analysis to investigate the effect of drug concentration on QT prolongation.


Input: Our meta-analysis of healthy volunteer data indicated no relationship between systemic losmapimod concentration and QT interval in healthy volunteers.

losmapimod


Input: Activation of AMP-activated Protein Kinase and Phosphorylation of Glycogen Synthase Kinase3 beta Mediate Ursolic Acid Induced Apoptosis in HepG2 Liver Cancer Cells.

AMP

Ursolic Acid


Input: Despite the antitumour effect of ursolic acid observed in several cancers, the underlying mechanism remains unclear.

ursolic acid


Input: Thus, in the present study, the roles of AMP-activated protein kinase (AMPK) and glycogen synthase kinase 3 beta (GSK3 beta) were examined in ursolic acid induced apoptosis in HepG2 hepatocellular carcinoma cells.

AMP


Input: Ursolic acid significantly exerted cytotoxicity, increased the sub-G1 population and the number of ethidium homodimer and terminal deoxynucleotidyl transferase (TdT) mediated dUTP nick end labeling positive cells in HepG2 cells.

Ursolic acid

ethidium

dUTP


Input: Also, ursolic acid enhanced the cleavages of poly-ADP-ribose polymerase (PARP) and caspase3, attenuated the expression of astrocyte elevated gene (AEG1) and survivin in HepG2 cells.

poly-ADP-ribose


Input: Interestingly, ursolic acid increased the phosphorylation of AMPK and coenzyme A carboxylase and also enhanced phosphorylation of GSK3 beta at inactive form serine 9, whereas ursolic acid attenuated the phosphorylation of AKT and mTOR in HepG2 cells.

ursolic acid

serine

ursolic acid


Input: Conversely, AMPK inhibitor compound C or GSK3 beta inhibitor SB216763 blocked the cleavages of PARP and caspase 3 induced by ursolic acid in HepG2 cells.

compound C

ursolic acid


Input: Furthermore, proteosomal inhibitor MG132 suppressed AMPK activation, GSK3 beta phosphorylation, cleaved PARP and deceased AEG-1 induced by ursolic acid in HepG2 cells.

ursolic acid


Input: Overall, our findings suggest that ursolic acid induced apoptosis in HepG2 cells via AMPK activation and GSK3 beta phosphorylation as a potent chemopreventive agent.

ursolic acid


Input: Copyright (c) 2013 John Wiley & Sons, Ltd.


Input: Design, synthesis, in vitro MAO-B inhibitory evaluation, and computational studies of some 6-nitrobenzothiazole-derived semicarbazones.

semicarbazones


Input: Monoamine oxidase B (MAO-B) is an important drug target for the treatment of neurological disorders.


Input: A series of 6-nitrobenzothiazole-derived semicarbazones were designed, synthesized, and evaluated as inhibitors of the rat brain MAO-B isoenzyme.

semicarbazones


Input: Most of the compounds were found to be potent inhibitors of MAO-B, with IC (50) values in the nanomolar to micromolar range.


Input: Molecular docking studies were performed with AutoDock 4. 2 to deduce the affinity and binding mode of these inhibitors toward the MAO-B active site.


Input: The free energies of binding (Delta G) and inhibition constants (K (i)) of the docked compounds were calculated by the Lamarckian genetic algorithm (LGA) of AutoDock 4. 2.


Input: Good correlations between the calculated and experimental results were obtained.


Input: 1-[(4-Chlorophenyl) (phenyl) methylene]-4-(6-nitrobenzothiazol-2-yl) semicarbazide emerged as the lead MAO-B inhibitor, with top ranking in both the experimental MAO-B assay (IC (50): 0. 004 +/- 0. 001 mu M) and in computational docking studies (K (i): 1. 08 mu M).

1-[(4-Chlorophenyl) (phenyl) methylene]-4-(6-nitrobenzothiazol-2-yl) semicarbazide


Input: Binding mode analysis of potent inhibitors suggests that these compounds are well accommodated by the MAO-B active site through stable hydrophobic and hydrogen bonding interactions.

hydrogen


Input: Interestingly, the 6-nitrobenzothiazole moiety is stabilized in the substrate cavity with the aryl or diaryl residues extending up into the entrance cavity of the active site.


Input: According to our results, docking experiments could be an interesting approach for predicting the activity and binding interactions of this class of semicarbazones against MAO-B.

semicarbazones


Input: Thus, a binding site model consisting of three essential pharmacophoric features is proposed, and this can be used for the design of future MAO-B inhibitors.


Input: Mutational analysis of the ribosome assembly GTPase RbgA provides insight into ribosome interaction and ribosome-stimulated GTPase activation.


Input: Ribosome biogenesis GTPase A protein (RbgA) is an essential GTPase required for the biogenesis of the 50S subunit in Bacillus subtilis.


Input: Homologs of RbgA are widely distributed in bacteria and eukaryotes and are implicated in ribosome assembly in the mitochondria, chloroplast and cytoplasm.


Input: Cells depleted of RbgA accumulate an immature large subunit that is missing key ribosomal proteins.


Input: RbgA, unlike many members of the Ras superfamily of GTPases, lacks a defined catalytic residue for carrying out guanosine triphosphate (GTP) hydrolysis.

guanosine triphosphate

GTP


Input: To probe RbgA function in ribosome assembly, we used a combined bioinformatics, genetic and biochemical approach.


Input: We identified a RNA-binding domain within the C-terminus of RbgA that is structurally similar to AmiR-NasR Transcription Anti-termination Regulator (ANTAR) domains, which are known to bind structured RNA.

C


Input: Mutation of key residues in the ANTAR domain altered RbgA association with the ribosome.


Input: We identified a putative catalytic residue within a highly conserved region of RbgA, His9, which is contained within a similar PGH motif found in elongation factor Tu (EF-Tu) that is required for GTP hydrolysis on interaction with the ribosome.

GTP


Input: Finally, our results support a model in which the GTPase activity of RbgA directly participates in the maturation of the large subunit rather than solely promoting dissociation of RbgA from the 50S subunit.


Input: Covalently functionalized double-walled carbon nanotubes combine high sensitivity and selectivity in the electrical detection of small molecules.

carbon


Input: Atom-thick materials such as single-walled carbon nanotubes (SWCNTs) and graphene exhibit ultrahigh sensitivity to chemical perturbation partly because all of the constituent atoms are surface atoms.

carbon

graphene


Input: However, low selectivity due to nonspecific binding on the graphitic surface is a challenging issue to many applications including chemical sensing.


Input: Here, we demonstrated simultaneous attainment of high sensitivity and selectivity in thin-film field effect transistors (TFTs) based on outer-wall selectively functionalized double-walled carbon nanotubes (DWCNTs).

carbon


Input: With carboxylic acid functionalized DWCNT TFTs, we obtained excellent gate modulation (on/off ratio as high as 4000) with relatively high ON currents at a CNT areal density as low as 35 ng/cm (2).

carboxylic acid


Input: The devices displayed an NH (3) sensitivity of 60 nM (or ~ 1 ppb), which is comparable to small molecule aqueous solution detection using state-of-the-art SWCNT TFT sensors while concomitantly achieving 6000 times higher chemical selectivity toward a variety of amine-containing analyte molecules over that of other small molecules.

NH (3)

amine


Input: These results highlight the potential of using covalently functionalized double-walled carbon nanotubes for simultaneous ultrahigh selective and sensitive detection of chemicals and illustrate some of the structural advantages of this double-wall materials strategy to nanoelectronics.

carbon


Input: A thermoplastic elastomer patch matrix for traditional Chinese medicine: design and evaluation.


Input: Abstract Objective: To design and evaluate a novel pressure sensitive adhesive (PSA) patch containing traditional Chinese medicine (TCM) using styrene-isoprene-styrene (SIS) copolymer.

styrene-isoprene-styrene

SIS


Input: Method: A mixture D-optimal design with ternary response surface diagram was employed in the optimization process.


Input: The proportions of SIS copolymer, tackifying resin and plasticizer were selected as the independent variables while tack force, peel strength of the patch and skin penetrability of methyl salicylate were selected as the dependent variables.

SIS

methyl salicylate


Input: The optimized patch was then evaluated including in vivo absorption, pharmacological activities and skin irritation, by comparing with a commercial patch based on natural rubber.


Input: Results: The optimized patch, which comprised 30. 0% SIS copolymer, 26. 6% tackifying resin and 43. 4% plasticizer, was superior to commercial patch in skin permeation, pharmacological activities and skin biocompatibility.

SIS


Input: Conclusion: SIS copolymer was a suitable substitute to natural rubber in producing patches containing TCM formula.

SIS


Input: High-contrast electrooptic modulation of a photonic crystal nanocavity by electrical gating of graphene.

graphene


Input: We demonstrate high-contrast electro-optic modulation of a photonic crystal nanocavity integrated with an electrically gated monolayer graphene.

graphene


Input: A silicon air-slot nanocavity provides strong overlap between the resonant optical field and graphene.

graphene


Input: Tuning the Fermi energy of the graphene layer to 0. 85 eV enables strong control of its optical conductivity at telecom wavelengths, which allows modulation of cavity reflection in excess of 10 dB for a swing voltage of only 1. 5 V.

graphene


Input: The cavity resonance at 1570 nm is found to undergo a shift in wavelength of nearly 2 nm, together with a 3-fold increase in quality factor.


Input: These observations enable a cavity-enhanced determination of graphene' s complex optical sheet conductivity at different doping levels.

graphene


Input: Our simple device demonstrates the feasibility of high-contrast, low-power, and frequency-selective electro-optic modulators in graphene-integrated silicon photonic integrated circuits.

graphene

silicon


Input: Species-dependent metabolism of a novel selective alpha 7 neuronal acetylcholine receptor agonist ABT-107.

acetylcholine


Input: Abstract 1.


Input: Metabolism of ABT-107 was investigated in in vitro hepatic systems, in rat and monkey receiving [(14) C] ABT-107, and in vivo plasma in rat, dog, monkey and human.

[(14) C] ABT-107


Input: In in vitro hepatic systems, ABT-107 was primarily cleared via oxidative metabolism, and proceeded via two parallel pathways.


Input: Pathway 1, ABT-107 was oxidized at the nitrogen of quinuclidine moiety to form M1.

nitrogen

quinuclidine


Input: Pathway 2, oxidation occurred at indole-containing moiety to form M2.

indole


Input: Metabolism via N-oxidation was predominant in dog and rat, while in monkey and human, metabolism proceeded primarily via oxidation of indole-containing moiety.

N

indole


Input: ABT-107 was extensively metabolized in vivo in rat and monkey.


Input: M1 was primarily found in rat urine and bile; whereas, M2 was the major metabolite in monkey urine and feces.


Input: M1 was the predominant circulating metabolite in dog and rat.


Input: M2 was the primary circulating metabolite in monkey and human.


Input: Enzymatic studies suggested M1 formation was primarily mediated by renal FMO1.


Input: CYP3A4, 1A2, 2J2 and 2D6 were primary enzymes catalyzing M2 formation.


Input: Biotransformation of ABT-107 in human and monkey is markedly different from that in dog and rat, suggesting that monkey is an appropriate model for predicting human biotransformation and toxicology of ABT-107.


Input: Unprecedented transformation of tetrathienoanthracene into pentacene on Ni (111).

tetrathienoanthracene

pentacene

Ni (111)


Input: The imaging and characterization of single-molecule reaction events is essential to both extending our basic understanding of chemistry and applying this understanding to challenges at the frontiers of technology, for example, in nanoelectronics.


Input: Specifically, understanding the behavior of individual molecules can elucidate processes critical to the controlled synthesis of materials for applications in multiple nanoscale technologies.


Input: Here, we report the synthesis of an important semiconducting organic molecule through an unprecedented reaction observed with submolecular resolution by scanning tunneling microscopy (STM) under ultrahigh vacuum (UHV) conditions.


Input: Our images reveal a sulfur abstraction and cyclization reaction that converts tetrathienoanthracene precursors into pentacene on the Ni (111) surface.

sulfur

tetrathienoanthracene

pentacene

Ni (111)


Input: The identity of the final reaction product was confirmed by time-of-flight secondary ion mass spectrometry (TOF-SIMS).


Input: This reaction has no known literature analogue, and highlights the power of local-probe techniques for exploring new chemical pathways.


Input: Endometrial thickness in women with ovulatory dysfunction.


Input: This study is designed to evaluate the relationship between endometrial thickness and clinical/biochemical parameters in women with chronic anovulation.


Input: One hundred and twenty women with ovulatory dysfunction were prospective included, endometrial thickness and endocrine and metabolic parameters were measured.


Input: The interval between the examination day and the day of the most recent menstrual bleeding (the anovulatory interval) for the studied subject was an average of 145 +/- 186 days.


Input: The endometrial thickness averaged 7. 1 +/- 3. 2 mm.


Input: Correlation analyses revealed that the endometrial thickness was positively correlated with body mass index but was not correlated with age, serum androgens, or estradiol (E2) levels.

androgens

estradiol


Input: We further classified the subjects into two groups based on endometrial thickness: Group A, endometrial thickness < 7 mm and Group B, endometrial thickness >= 7 mm.


Input: The anovulatory interval, follicle-stimulating hormone, luteinizing hormone, E2 and androgen levels were not significantly different between Groups A and B.

androgen


Input: Group B had higher body weight and more risk for metabolic syndrome.


Input: We concluded that endometrial thickness in women with ovulatory dysfunction is positively correlated with body weight status but is not correlated with serum androgens or E2 levels.

androgens


Input: The macrocyclic peptide natural product CJ-15, 208 is orally active and prevents reinstatement of extinguished cocaine-seeking behavior.

CJ-15, 208

cocaine


Input: The macrocyclic tetrapeptide natural product CJ-15, 208 (cyclo [Phe-d-Pro-Phe-Trp]) exhibited both dose-dependent antinociception and kappa opioid receptor (KOR) antagonist activity after oral administration.

macrocyclic tetrapeptide

CJ-15, 208

cyclo [Phe-d-Pro-Phe-Trp]


Input: CJ-15, 208 antagonized a centrally administered KOR selective agonist, providing strong evidence it crosses the blood-brain barrier to reach KOR in the CNS.

CJ-15, 208


Input: Orally administered CJ-15, 208 also prevented both cocaine-and stress-induced reinstatement of extinguished cocaine-seeking behavior in the conditioned place preference assay in a time-and dose-dependent manner.

CJ-15, 208

cocaine

cocaine


Input: Thus, CJ-15, 208 is a promising lead compound with a unique activity profile for potential development, particularly as a therapeutic to prevent relapse to drug-seeking behavior in abstinent subjects.

CJ-15, 208


Input: Levels of thrombin activatable fibrinolysis inhibitor in gestational diabetes mellitus.


Input: Thrombin-activatable fibrinolysis inhibitor (TAFI) is a procarboxypeptidase, which is synthesised in liver and activated by thrombin and the thrombin-thrombomodulin complex.


Input: TAFI suppresses fibrinolysis by removing carboxy-terminal lysine residues from partially degraded fibrin.

carboxy

lysine


Input: In this study we aimed to assess the circulating levels of TAFI antigen,' a fibrinolytic parameter' in women with gestational diabetes (GDM).


Input: Thirty-four pregnant women with GDM and 50 pregnant women with normal glucose tolerance were included in the study.


Input: Plasma TAFI antigen levels were significantly higher in pregnant women with GDM when compared with controls.


Input: Increased TAFI levels may contribute to the decreased fibrinolytic potency, causing a thrombophilic state.


Input: GDM is regarded as a specific form of diabetes, and it could in addition be a predictor of type 2 diabetes mellitus in the future and the risk of complications due to hypercoagulability increases in this disease.


Input: Increased TAFI levels may also have a role in increased risk of hypercoagulability.


Input: Embelin accelerates cutaneous wound healing in diabetic rats.

Embelin


Input: This study reports the effect of embelin (1) on cutaneous wound in streptozotocin (STZ)-induced diabetic rats.

embelin

streptozotocin

STZ


Input: The effect was studied using excision, incision, and dead space models.


Input: In diabetic rats, topical application of embelin 5% (w/w) ointment showed a significant increase in wound contraction and better epithelialization, thereby facilitating the healing.

embelin


Input: Embelin was also active by the oral route (25 and 50 mg/kg) in the incision and dead space wound models.

Embelin


Input: In incision wound model, wound granulation tissues were removed on 8th post-wounding day, and the hydroxyproline, hexosamine, total protein, and DNA contents were determined.

hydroxyproline

hexosamine


Input: In STZ diabetic rats, topical and oral applications of embelin showed an increase in hydroxyproline, hexosamine, total protein, and DNA contents.

STZ

embelin

hydroxyproline

hexosamine


Input: It also showed a significant increase in wound breaking strength.


Input: Embelin significantly increased granuloma tissue weight and breaking strength in dead space model.

Embelin


Input: These results indicated that embelin accelerated wound healing in diabetic rat.

embelin


Input: Jatropholane-type diterpenes from Euphorbia sikkimensis.

Jatropholane

diterpenes


Input: Four new jatropholane-type diterpenes (1-4), named sikkimenoids A-D, were isolated from the aerial parts of Euphorbia sikkimensis.

jatropholane

diterpenes

sikkimenoids A-D


Input: The structural elucidations of 1-4 were accomplished by extensive NMR analyses, and their absolute configurations were established by ECD calculations.


Input: Compound 2 exhibited weak antiangiogenic activity with an IC (50) value of 43. 0 mu M when evaluated using a zebrafish model.


Input: Significant interaction between RETN-420 G/G genotype and lower BMI on decreased risk of type 2 diabetes mellitus (T2DM) in Japanese--the J-MICC Study.


Input: We examined the association of the RETN (resistin)-420 C > G polymorphism (rs1862513) with risk of diabetes mellitus (DM), considering lifestyle factors, in Japanese.


Input: Subjects were participants of J-MICC Study, where 2, 651 participants aged 35-69 years provided their blood for genotyping and lifestyle data after informed consent.


Input: Odds ratio (OR) of DM for RETN-420 G/G genotype was estimated using unconditional logistic regression model.


Input: Statistically significant interaction on risk of DM was observed between RETN-420 G/G genotype and BMI < 25 (OR for interaction = 0. 12; P = 0. 046), and when subjects with RETN-420 C/C + C/G and BMI >= 25 (n = 69 for DM and 544 for non-DM) were defined as the reference, the adjusted ORs for subjects with RETN-420 G/G genotype and BMI > 25 (n = 10 for DM and 111 for non-DM), RETN-420 C/C + C/G and BMI < 25 (n = 81 for DM and 1, 605 for non-DM), and RETN-420 G/G and BMI < 25 (n = 1 for DM and 230 for non-DM) were demonstrated to be 0. 72 (95% confidence interval: 0. 36-1. 46), 0. 40 (0. 28-0. 56) and 0. 03 (0. 005-0. 25), respectively.


Input: The present study revealed the significant interaction of RETN-420 G/G genotype with lower BMI on the decreased risk of DM, but the direction was opposite to the reported ones in Japanese.


Input: We should be careful in interpretation of the present study results because of the limited sample sizes.


Input: Further investigation of this association as well as of the actual biological roles of RETN in the genesis of human metabolic disorders including DM will be required.


Input: Nucleophosmin mutations alter its nucleolar localization by impairing G-quadruplex binding at ribosomal DNA.


Input: Nucleophosmin (NPM1) is an abundant nucleolar protein implicated in ribosome maturation and export, centrosome duplication and response to stress stimuli.


Input: NPM1 is the most frequently mutated gene in acute myeloid leukemia.


Input: Mutations at the C-terminal domain led to variant proteins that aberrantly and stably translocate to the cytoplasm.

C


Input: We have previously shown that NPM1 C-terminal domain binds with high affinity G-quadruplex DNA.

C


Input: Here, we investigate the structural determinants of NPM1 nucleolar localization.


Input: We show that NPM1 interacts with several G-quadruplex regions found in ribosomal DNA, both in vitro and in vivo.


Input: Furthermore, the most common leukemic NPM1 variant completely loses this activity.


Input: This is the consequence of G-quadruplex-binding domain destabilization, as mutations aimed at refolding the leukemic variant also result in rescuing the G-quadruplex-binding activity and nucleolar localization.


Input: Finally, we show that treatment of cells with a G-quadruplex selective ligand results in wild-type NPM1 dislocation from nucleoli into nucleoplasm.


Input: In conclusion, this work establishes a direct correlation between NPM1 G-quadruplex binding at rDNA and its nucleolar localization, which is impaired in the acute myeloid leukemia-associated protein variants.


Input: Drug metabolism and transport during pregnancy: how does drug disposition change during pregnancy and what are the mechanisms that cause such changes?


Input: There is increasing evidence that pregnancy alters the function of drug-metabolizing enzymes and drug transporters in a gestational-stage and tissue-specific manner.


Input: In vivo probe studies have shown that the activity of several hepatic cytochrome P450 enzymes, such as CYP2D6 and CYP3A4, is increased during pregnancy, whereas the activity of others, such as CYP1A2, is decreased.


Input: The activity of some renal transporters, including organic cation transporter and P-glycoprotein, also appears to be increased during pregnancy.


Input: Although much has been learned, significant gaps still exist in our understanding of the spectrum of drug metabolism and transport genes affected, gestational age-dependent changes in the activity of encoded drug metabolizing and transporting processes, and the mechanisms of pregnancy-induced alterations.


Input: In this issue of Drug Metabolism and Disposition, a series of articles is presented that address the predictability, mechanisms, and magnitude of changes in drug metabolism and transport processes during pregnancy.


Input: The articles highlight state-of-the-art approaches to studying mechanisms of changes in drug disposition during pregnancy, and illustrate the use and integration of data from in vitro models, animal studies, and human clinical studies.


Input: The findings presented show the complex inter-relationships between multiple regulators of drug metabolism and transport genes, such as estrogens, progesterone, and growth hormone, and their effects on enzyme and transporter expression in different tissues.

estrogens

progesterone


Input: The studies provide the impetus for a mechanism-and evidence-based approach to optimally managing drug therapies during pregnancy and improving treatment outcomes.


Input: Environmental Survey Meta-analysis Reveals Hidden Diversity among Unicellular Opisthokonts.


Input: The Opisthokonta clade includes Metazoa, Fungi, and several unicellular lineages, such as choanoflagellates, filastereans, ichthyosporeans, and nucleariids.


Input: To date, studies of the evolutionary diversity of opisthokonts have focused exclusively on metazoans, fungi, and, very recently, choanoflagellates.


Input: Thus, very little is known about diversity among the filastereans, ichthyosporeans, and nucleariids.


Input: To better understand the evolutionary diversity and ecology of the opisthokonts, here we analyze published environmental data from nonfungal unicellular opisthokonts and report 18S ribosomal DNA phylogenetic analyses.


Input: Our data reveal extensive diversity among all unicellular opisthokonts, except for the filastereans.


Input: We identify several clades that consist exclusively of environmental sequences, especially among ichthyosporeans and choanoflagellates.


Input: Moreover, we show that the ichthyosporeans represent a significant percentage of overall unicellular opisthokont diversity, with a greater ecological role in marine environments than previously believed.


Input: Our results provide a useful phylogenetic framework for future ecological and evolutionary studies of these poorly known lineages.


Input: Lack of dosage compensation accompanies the arrested stage of sex chromosome evolution in ostriches.


Input: Sex chromosome evolution is usually seen as a process that, once initiated, will inevitably progress toward an advanced stage of degeneration of the nonrecombining chromosome.


Input: However, despite evidence that avian sex chromosome evolution was initiated > 100 Ma, ratite birds have been trapped in an arrested stage of sex chromosome divergence.


Input: We performed RNA sequencing of several tissues from male and female ostriches and assembled the transcriptome de novo.


Input: A total of 315 Z-linked genes fell into two categories: those that have equal expression level in the two sexes (for which Z-W recombination still occurs) and those that have a 2-fold excess of male expression (for which Z-W recombination has ceased).


Input: We suggest that failure to evolve dosage compensation has constrained sex chromosome divergence in this basal avian lineage.


Input: Our results indicate that dosage compensation is a prerequisite for, not only a consequence of, sex chromosome evolution.


Input: Managing scientific, technical and regulatory innovation in regulated bioanalysis: a discussion paper from the European Bioanalysis Forum.


Input: On 12-13 June 2012, the European Bioanalysis Forum hosted its third Focus Meeting in Brussels (Belgium).


Input: At the meeting, a panel discussion was held on the hurdles that the bioanalytical community encounters when adopting new technologies or managing regulated bioanalysis expectations around emerging technologies.


Input: Over the last few years, the industry has seen many new technologies maturing.