Input: Electrochemical analysis of bacterial cells exposed to Cu (2 +) ions provides new insights into the mechanistic aspect of Cu (2 +) ion reduction within the bacterial cell and indicates a strong link between the silver and copper resistance machinery of bacteria in the context of metal ion reduction.

Cu (2 +)

Cu (2 +)

silver

copper


Input: The outcomes of this study take us a step closer towards designing rational strategies for biosynthesis of different metal nanoparticles using microorganisms.


Input: Membrane protein native state discrimination by implicit membrane models.


Input: Four implicit membrane models [IMM1, generalized Born (GB)-surface area-implicit membrane (GBSAIM), GB with a simple switching (GBSW), and heterogeneous dielectric GB (HDGB)] were tested for their ability to discriminate the native conformation of five membrane proteins from 450 decoys generated by the Rosetta-Membrane program.


Input: The energy ranking of the native state and Z-scores were used to assess the performance of the models.


Input: The effect of membrane thickness was examined and was found to be substantial.


Input: Quite satisfactory discrimination was achieved with the all-atom IMM1 and GBSW models at 25. 4 A thickness and with the HDGB model at 28. 5 A thickness.


Input: The energy components by themselves were not discriminative.


Input: Both van der Waals and electrostatic interactions contributed to native state discrimination, to a different extent in each model.


Input: Computational efficiency of the models decreased in the order: extended-atom IMM1 > all-atom IMM1 > GBSAIM > GBSW > HDGB.


Input: These results encourage the further development and use of implicit membrane models for membrane protein structure prediction.


Input: 2-Phenoxy-nicotinamides are potent agonists at the bile acid receptor GPBAR1 (TGR5).

bile acid


Input: Potency with potential: 2-Phenoxy-nicotinamides were identified as potent agonists at the GPBAR1 receptor, a target in the treatment of obesity, type 2 diabetes and metabolic syndrome.


Input: Extensive structure-activity relationship studies supported by homology modeling and docking resulted in the identification of optimized GPBAR1 agonists, potent against both human and mouse receptors, endowed with favorable physicochemical properties and good metabolic stability.


Input: Effect of ganglioside GM3 synthase gene knockout on the glycoprotein N-glycan profile of mouse embryonic fibroblast.

ganglioside


Input: The structural and clinical significance of cellular glycoproteins and glycosphingolipids (GSLs) are often separately discussed.


Input: Considering the biosynthetic pathway of glycoconjugates, glycans of cell-surface glycoproteins and GSLs might partially share functions in maintaining cellular homeostatis.


Input: The purpose of this study is to establish a general and comprehensive glycomics protocol for cellular GSLs and N-glycans of glycoproteins.


Input: To test the feasibility of a glycoblotting-based protocol, whole glycans released both from GSLs and glycoproteins were profiled concurrently by using GM3 synthase-deficient mouse embryonic fibroblast GM3 (-/-).


Input: GM3 (-/-) cells did not synthesize GM3 or any downstream product of GM3 synthase.


Input: Instead, expression levels of o-series gangliosides involving GM1-b and GD1-alpha increased dramatically, whereas a-/b-series gangliosides were predominantly detected in wild-type (WT) cells.

gangliosides


Input: We also discovered that glycoprotein N-glycan profiles of GM3 (-/-) cells are significantly altered as compared to WT cells, although GM3 synthase is responsible only for GSLs synthesis and is not associated with glycoprotein N-glycan biosynthesis.


Input: The present approach allows for high-throughput profiling of cellular glycomes enriched by different classes of glycoconjugates, and our results demonstrated that gene knockout of the enzymes responsible for GSL biosynthesis significantly influences the N-glycans of glycoproteins.


Input: Organotins: A review of their reproductive toxicity, biochemistry, and environmental fate.

Organotins


Input: The review purposes are to (1) evaluate the experimental evidence for adverse effects on reproduction and metabolism and (2) identify the current knowledge of analytical procedures, biochemistry and environmental aspects relating to organotins.

organotins


Input: Organotins are pollutants that are used as biocides in antifouling paints.

Organotins


Input: They produce endocrine-disrupting effects in mollusks, such as imposex.


Input: In rodents, organotin exposure induces developmental and reproductive toxicity as well as alteration of metabolic homeostasis through its action as an obesogen.

organotin


Input: The adverse effects that appear in rodents have raised concerns about organotins' potential health risk to humans in relation to organotin exposure.

organotins

organotin


Input: At present, triorganotin, such as tributyltin, have been demonstrated to produce imposex, and mammalian reproductive and metabolic toxicity.

triorganotin

tributyltin


Input: For most mammals, triorganotin exposure predominantly occurs through the ingestion, and this compound can cross the placenta.

triorganotin


Input: With these risks in mind, it is important to improve our knowledge of organotins' effects on environmental health.

organotins


Input: Multiple microRNAs may regulate the DNA repair enzyme uracil-DNA glycosylase.

uracil


Input: Human nuclear uracil-DNA glycosylase UNG2 is essential for post-replicative repair of uracil in DNA, and UNG2 protein and mRNA levels rapidly decline in G2/M phase.

uracil

uracil


Input: Previous work has demonstrated regulation of UNG2 at the transcriptional level, as well as by protein phosphorylation and ubiquitylation.


Input: UNG2 mRNA, encoded by the UNG gene, contains a long 3' untranslated region (3' UTR) of previously unknown function.


Input: Here, we demonstrate that several conserved regions in the 3' UTR are potential seed sites for microRNAs (miRNAs), such as miR-16, miR-34c, and miR-199a.


Input: Our results show that these miRNAs down-regulate UNG activity, UNG mRNA, and UNG protein levels.


Input: Down-regulation was dependent on the 3' UTR, indicating that the miRNAs directly target the conserved seed sites in the 3' UTR.


Input: These results add miRNAs as a new modality to UNG' s increasing list of complex regulatory mechanisms.


Input: Quantitative characterization of non-contact microdispensing technologies for the sub-microliter range.


Input: This work describes how to effectively compare non-contact dispensing technologies for automated liquid handling under high-throughput screening (HTS) conditions in the range of 0. 05-10 mu l.


Input: Exemplarily, we characterize five established technologies and categorize them into valve-based and positive displacement-based technologies.


Input: Furthermore we introduce dispensing accuracy and precision in an' intra-run',' inter-run' and' tip-to-tip' context as universally applicable performance parameters.


Input: A NIST traceable spectrophotometric measurement method is utilized for experimental characterization.


Input: It yields an Intra-Run CV (Inter-Run CV) between 0. 4% to 7. 7% (0. 5 to 10. 9%) and a Tip-to-Tip CV between 1. 4% and 9. 9% for target volumes < 1 mu l.


Input: An absolute accuracy of better than 5. 0% is generally difficult to achieve in the sub-microliter range.


Input: Targeting VEGF signalling via the neuropilin co-receptor.


Input: The blockade of tumour vascularisation and angiogenesis continues to be a focus for drug development in oncology and other pathologies.


Input: Historically, targeting vascular endothelial growth factor (VEGF) activity and its association with VEGF receptors (VEGFRs) has represented the most promising line of attack.


Input: More recently, the recognition that VEGFR co-receptors, neuropilin-1 and-2 (NRP1 and NRP2), are also engaged by specific VEGF isoforms in tandem with the VEGFRs has expanded the landscape for the development of modulators of VEGF-dependent signalling.


Input: Here, we review the recent structural characterisation of VEGF interactions with NRP subdomains and the impact this has had on drug development activity in this area.


Input: Oxidative modification of neurofilament-L and neuronal cell death induced by the catechol neurotoxin, tetrahydropapaveroline.

catechol

tetrahydropapaveroline


Input: Tetrahydropapaveroline (THP), which is an endogenous neurotoxin, has been suspected to be associated with dopaminergic neurotoxicity of l-DOPA.

Tetrahydropapaveroline

THP

l-DOPA


Input: In this study, we examined oxidative modification of neurofilament-L (NF-L) and neuronal cell death induced by THP.

THP


Input: When disassembled NF-L was incubated with THP, protein aggregation was increased in a time-and THP dose-dependent manner.

THP

THP


Input: The formation of carbonyl compounds and dityrosine were observed in the THP-mediated NF-L aggregates.

carbonyl

dityrosine

THP


Input: Radical scavengers reduced THP-mediated NF-L modification.

THP


Input: These results suggest that the modification of NF-L by THP may be due to oxidative damage resulting from the generation of reactive oxygen species (ROS).

THP

oxygen


Input: When THP exposed NF-L was subjected to amino acid analysis, glutamate, proline and lysine residues were found to be particularly sensitive.

THP

amino acid

glutamate

proline

lysine


Input: We also investigated the effects of copper ions on THP-mediated NF-L modification.

copper

THP


Input: At a low concentration of THP, copper ions enhanced the modification of NF-L.

THP

copper


Input: Treatment of C6 astrocyte cells with THP led to a concentration-dependent reduction in cell viability.

THP


Input: When these cells were treated with 100 mu M THP, the levels of ROS increased 3. 5-fold compared with control cells.

THP


Input: Furthermore, treatment of cells with THP increased NF-L aggregate formation, suggesting the involvement of NF-L modification in THP-induced cell damage.

THP

THP


Input: Synthesis and antibacterial evaluation of novel 11, 4''-disubstituted azithromycin analogs with greatly improved activity against erythromycin-resistant bacteria.

11, 4''-disubstituted azithromycin

erythromycin


Input: A series of novel 11, 4''-disubstituted azithromycin analogs were synthesized and evaluated for their antibacterial activity.

11, 4''-disubstituted azithromycin


Input: All the 11, 4''-disubstituted analogs exhibited excellent activity (0. 03-0. 12 mu g/ml) against erythromycin-susceptible Streptococcus pneumoniae, and significantly improved activity against three phenotypes of erythromycin-resistant S. pneumoniae compared with erythromycin A, clarithromycin or azithromycin.

erythromycin

erythromycin

erythromycin A

clarithromycin

azithromycin


Input: Among them, compounds 26-28 showed the most potent activity (0. 25, 0. 03 and 2 mu g/ml) against S. pneumoniae expressing the erm gene, the mef gene and the erm and mef genes, respectively.


Input: In addition, compound 28 was the most effective (0. 03 and 0. 12 mu g/ml) against erythromycin-susceptible S. pneumoniae and Staphylococcus aureus as well.

erythromycin


Input: It is noteworthy that the most active compounds described above possess the same terminal 3, 5-dinitrophenyl groups on their C-4'' bisamide side chains.

3, 5-dinitrophenyl

bisamide


Input: Neutral and charged phosphine/scorpionate copper (I) complexes: effects of ligand assembly on their antiproliferative activity.

phosphine/scorpionate copper (I) complexes


Input: Ligand-exchange reactions of copper (I) precursors ([Cu (CH (3) CN) (4)] BF (4), CuCl) with a panel of bis (azolyl) borates or poly (pyrazolyl) methanes and a tertiary monodentate phosphine (PTA = 1, 3, 5-triaza-7-phosphaadamantane, PCN = tris (cyanoethyl) phosphine) produced two series of heteroleptic, either' 2 + 1 + 1'-or' 3 + 1'-type complexes, which have been characterized by elemental analysis, FT-IR, ESI-MS and multinuclear (31) P and (1) H NMR.

copper (I)

[Cu (CH (3) CN) (4)] BF (4)

CuCl

bis (azolyl) borates

poly (pyrazolyl) methanes

tertiary monodentate phosphine

PTA

1, 3, 5-triaza-7-phosphaadamantane

PCN

tris (cyanoethyl) phosphine

(31) P

(1) H


Input: ' 2 + 1 + 1'-type complexes include a N, N-bidentate chelate and two monodentate phosphines (1-8) and' 3 + 1'-type complexes comprise a N, N, O-or N, N, N-tridentate chelate and one monodentate phosphine (9-12).

N

N

phosphines

N

N

O

N

N

N

phosphine


Input: All these complexes adopt a four-coordinate, tetrahedral geometry.


Input: ' 3 + 1' complexes show better red-ox stability and a greater tendency to retain the native' 3 + 1' mixed-ligand structure.


Input: Conversely,' 2 + 1 + 1' complexes exhibit increased propensity to dissociation as shown by ESI-MS measurements and X-ray structure determination at low temperature (150 K) of the polymeric complex {[H (2) B (tz (NO2)) (2)] Cu [PCN]} (n) 6b.

{[H (2) B (tz (NO2)) (2)] Cu [PCN]} (n)


Input: In this complex, either the bis (triazolyl) borate and the PCN ligands act as bidentate, with PCN being also the mu (2)-bridiging linker between adjacent monomers.

bis (triazolyl) borate

PCN

PCN


Input: Compound 6b is the first reported example of a polymeric PCN compound with a tetra-coordinate metal centre.

PCN


Input: Cytotoxic activity of all compounds has been evaluated by MTT test against a panel of several human tumor cell lines including examples of breast (MCF-7), colon (HCT-15 and LoVo), lung (A549), cervix (A431) and ovarian (2008 and its cisplatin resistant variant, C13 *) carcinoma, melanoma (A375) and promyelocytic leukemia (HL60).

MTT

cisplatin


Input: Copper complexes generally show in vitro antitumour activity comparable to that of cisplatin.

Copper

cisplatin


Input: In particular, neutral' 3 + 1'-type complexes 9 and 10, show IC (50) values appreciably lower than those exhibited by the reference metallodrug.


Input: Utilizing Eisenia andrei to assess the ecotoxicity of platinum mine tailings disposal facilities.

platinum


Input: South Africa is an important platinum mining country which results in environmental impacts due to the construction of tailing disposal facilities (TDFs).

platinum


Input: It is unclear what the effects of ageing are on the ecotoxicity of TDFs and whether it increases or decreases over time.


Input: The aim of this study was to determine the ecotoxicity of differently aged TDFs by investigating earthworm (Eisenia andrei) responses viz. growth, reproduction, neutral red retention times (NRRT) and tissue metal concentrations.


Input: Further, to evaluate the status of these in terms of a geoaccumulation index (I (geo)), pollution index and integrated pollution index.


Input: Results indicated that earthworms showed reduced reproductive success (hatchlings per cocoon) and decreased NRRT in all the sites.


Input: Juveniles per cocoon between all of the different treatment groups were; control (2. 83 +/- 0. 54) > site 2 (20 years old; 1. 83 +/- 0. 27) > sites 1 and 3 (40 years old; 1. 06 +/- 0. 15 and 6 years old; 0. 88 +/- 0. 39).


Input: This might be ascribed to the elevated levels of Cr (+/- 200 to 1, 166 mu g g (-1)) and Ni (+/- 100 to 316 mu g g (-1)) in all of the sites.

Cr

Ni


Input: Earthworms did not bioaccumulate metals with bioconcentration factors for all the different treatments < 0. 01.


Input: Studies like these could be useful when establishing a ranking of TDFs in the future to provide legislative institutions with an indication of the environmental liabilities of platinum mines.

platinum


Input: Oxidative folding of peptides with cystine-knot architectures: kinetic studies and optimization of folding conditions.

cystine


Input: Bioactive peptides often contain several disulfide bonds that provide the main contribution to conformational rigidity and structural, thermal, or biological stability.

disulfide


Input: Among them, cystine-knot peptides-commonly named " knottins "-make up a subclass with several thousand natural members.

cystine


Input: Hence, they are considered promising frameworks for peptide-based pharmaceuticals.


Input: Although cystine-knot peptides are available through chemical and recombinant synthetic routes, oxidative folding to afford the bioactive isomers still remains a crucial step.

cystine


Input: We therefore investigated the oxidative folding of ten protease-inhibiting peptides from two knottin families, as well as that of an HIV entry inhibitor and of aprotinin, under two conventional sets of folding conditions and by a newly developed procedure.


Input: Kinetic studies identified folding conditions that resulted in correctly folded miniproteins with high rates of conversion even for highly hydrophobic and aggregation-prone peptides in concentrated solutions.


Input: Identification and characterization of a potent activator of p53-independent cellular senescence via a small-molecule screen for modifiers of the integrated stress response.


Input: The Integrated Stress Response (ISR) is a signaling program that enables cellular adaptation to stressful conditions like hypoxia and nutrient deprivation in the tumor microenvironment.


Input: An important effector of the ISR is activating transcription factor 4 (ATF4), a transcription factor that regulates genes involved in redox homeostasis and amino acid metabolism and transport.

amino acid


Input: Because both inhibition and overactivation of the ISR can induce tumor cell death, modulators of ATF4 expression could prove to be clinically useful.


Input: In this study, chemical libraries were screened for modulators of ATF4 expression.


Input: We identified one compound, E235 (N-(1-benzyl-piperidin-4-yl)-2-(4-fluoro-phenyl)-benzo [d] imidazo [2, 1-b] thiazole-7-carboxamide), that activated the ISR and dose-dependently increased levels of ATF4 in transformed cells.

E235 (N-(1-benzyl-piperidin-4-yl)-2-(4-fluoro-phenyl)-benzo [d] imidazo [2, 1-b] thiazole-7-carboxamide)


Input: A dose-dependent decrease in viability was observed in several mouse and human tumor cell lines, and knockdown of ATF4 significantly increased the antiproliferative effects of E235.


Input: Interestingly, low mu M doses of E235 induced senescence in many cell types, including HT1080 human fibrosarcoma and B16F10 mouse melanoma cells.


Input: E235-mediated induction of senescence was not dependent on p21 or p53; however, p21 conferred protection against the growth inhibitory effects of E235.


Input: Treatment with E235 resulted in an increase in cells arrested at the G2/M phase with a concurrent decrease in S-phase cells.


Input: E235 also activated DNA damage response signaling, resulting in increased levels of Ser15-phosphorylated p53, gamma-H2AX, and phosphorylated checkpoint kinase 2 (Chk2), although E235 does not appear to cause physical DNA damage.


Input: Induction of gamma-H2AX was abrogated in ATF4 knockdown cells.


Input: Together, these results suggest that modulation of the ISR pathway with the small molecule E235 could be a promising antitumor strategy.


Input: PHF6 regulates cell cycle progression by suppressing ribosomal RNA synthesis.


Input: Mutation of PHF6, which results in the X-linked mental retardation disorder B o rjeson-Forssman-Lehmann syndrome, is also present in about 38% of adult T-cell acute lymphoblastic leukemias and 3% of adult acute myeloid leukemias.


Input: However, it remains to be determined exactly how PHF6 acts in vivo and what functions of PHF6 may be associated with its putative tumor suppressor function.


Input: Here, we demonstrate that PHF6 is a nucleolus, ribosomal RNA promoter-associated protein.


Input: PHF6 directly interacts with upstream binding factor (UBF) through its PHD1 domain and suppresses ribosomal RNA (rRNA) transcription by affecting the protein level of UBF.


Input: Knockdown of PHF6 impairs cell proliferation and arrests cells at G (2)/M phase, which is accompanied by an increased level of phosphorylated H2AX, indicating that PHF6 deficiency leads to the accumulation of DNA damage in the cell.


Input: We found that increased DNA damage occurs at the ribosomal DNA (rDNA) locus in PHF6-deficient cells.


Input: This effect could be reversed by knocking down UBF or overexpressing RNASE1, which removes RNA-DNA hybrids, suggesting that there is a functional link between rRNA synthesis and genomic stability at the rDNA locus.


Input: Together, these results reveal that the key function of PHF6 is involved in regulating rRNA synthesis, which may contribute to its roles in cell cycle control, genomic maintenance, and tumor suppression.


Input: Understanding how noncatalytic carbohydrate binding modules can display specificity for xyloglucan.

carbohydrate


Input: Plant biomass is central to the carbon cycle and to environmentally sustainable industries exemplified by the biofuel sector.

carbon


Input: Plant cell wall degrading enzymes generally contain noncatalytic carbohydrate binding modules (CBMs) that fulfil a targeting function, which enhances catalysis.

carbohydrate


Input: CBMs that bind beta-glucan chains often display broad specificity recognizing beta 1, 4-glucans (cellulose), beta 1, 3-beta 1, 4-mixed linked glucans and xyloglucan, a beta 1, 4-glucan decorated with alpha 1, 6-xylose residues, by targeting structures common to the three polysaccharides.

alpha 1, 6-xylose


Input: Thus, CBMs that recognize xyloglucan target the beta 1, 4-glucan backbone and only accommodate the xylose decorations.


Input: Here we show that two closely related CBMs, CBM65A and CBM65B, derived from EcCel5A, a Eubacterium cellulosolvens endoglucanase, bind to a range of beta-glucans but, uniquely, display significant preference for xyloglucan.


Input: The structures of the two CBMs reveal a beta-sandwich fold.


Input: The ligand binding site comprises the beta-sheet that forms the concave surface of the proteins.


Input: Binding to the backbone chains of beta-glucans is mediated primarily by five aromatic residues that also make hydrophobic interactions with the xylose side chains of xyloglucan, conferring the distinctive specificity of the CBMs for the decorated polysaccharide.

xylose


Input: Significantly, and in contrast to other CBMs that recognize beta-glucans, CBM65A utilizes different polar residues to bind cellulose and mixed linked glucans.


Input: Thus, Gln (106) is central to cellulose recognition, but is not required for binding to mixed linked glucans.

Gln


Input: This report reveals the mechanism by which beta-glucan-specific CBMs can distinguish between linear and mixed linked glucans, and show how these CBMs can exploit an extensive hydrophobic platform to target the side chains of decorated beta-glucans.


Input: EBEC 2012--an energetic time in Freiburg.


Input: The seventeenth European Bioenergetics Conference (EBEC) took place in September 2012 at the Albert-Ludwigs-University in Freiburg, Germany, and was hosted by Thorsten Friedrich.


Input: The conference is a biannual event that brings together researchers from across the globe to discuss progress in this diverse and challenging field.


Input: The bovine ATP-binding cassette transporter ABCG2 Tyr581Ser single-nucleotide polymorphism increases milk secretion of the fluoroquinolone danofloxacin.

ATP

danofloxacin


Input: The bovine adenosine triphosphate-binding cassette transporter G2 (ABCG2/breast cancer resistance protein) polymorphism Tyr581Ser (Y581S) has recently been shown to increase in vitro transepithelial transport of antibiotics.

adenosine triphosphate


Input: Since this transporter has been extensively related to the active secretion of drugs into milk, the potential in vivo effect of this polymorphism on secretion of xenobiotics in livestock could have striking consequences for milk production, the dairy industry, and public health.


Input: Our purpose was to study the in vivo effect of this polymorphism on the secretion of danofloxacin, a widely used veterinary antibiotic, into milk.

danofloxacin


Input: Danofloxacin (1. 25 mg/kg) was administered to six Y/Y 581 homozygous and six Y/S 581 heterozygous lactating cows, and plasma and milk samples were collected and analyzed by high-performance liquid chromatography.

Danofloxacin


Input: No differences were found in the pharmacokinetic parameters of danofloxacin in plasma between the two groups of animals.

danofloxacin


Input: In contrast, Y/S heterozygous cows showed a 2-fold increase in danofloxacin levels in milk.

danofloxacin


Input: In addition, the pharmacokinetic elimination parameters, mean residence time and elimination half-life, were significantly lower in the milk of the animals carrying the Y/S polymorphism.


Input: These in vivo results are in agreement with our previously published in vitro data, which showed a greater capacity of the S581 variant in accumulation assays, and demonstrate, for the first time, an important effect of the Y581S single-nucleotide polymorphism on antibiotic secretion into cow milk.


Input: These findings could be extended to other ABCG2 substrates, and may be relevant for the treatment of mastitis and for the design of accurate and novel strategies to handle milk residues.


Input: Sequences associated with centromere competency in the human genome.


Input: Centromeres, the sites of spindle attachment during mitosis and meiosis, are located in specific positions in the human genome, normally coincident with diverse subsets of alpha satellite DNA.


Input: While there is strong evidence supporting the association of some subfamilies of alpha satellite with centromere function, the basis for establishing whether a given alpha satellite sequence is or is not designated a functional centromere is unknown, and attempts to understand the role of particular sequence features in establishing centromere identity have been limited by the near identity and repetitive nature of satellite sequences.


Input: Utilizing a broadly applicable experimental approach to test sequence competency for centromere specification, we have carried out a genomic and epigenetic functional analysis of endogenous human centromere sequences available in the current human genome assembly.


Input: The data support a model in which functionally competent sequences confer an opportunity for centromere specification, integrating genomic and epigenetic signals and promoting the concept of context-dependent centromere inheritance.


Input: Equilibrium gold nanoclusters quenched with biodegradable polymers.


Input: Although sub-100 nm nanoclusters of metal nanoparticles are of interest in many fields including biomedical imaging, sensors, and catalysis, it has been challenging to control their morphologies and chemical properties.


Input: Herein, a new concept is presented to assemble equilibrium Au nanoclusters of controlled size by tuning the colloidal interactions with a polymeric stabilizer, PLA (1k)-b-PEG (10k)-b-PLA (1k).

Au

PLA

PEG

PLA


Input: The nanoclusters form upon mixing a dispersion of ~ 5 nm Au nanospheres with a polymer solution followed by partial solvent evaporation.

Au


Input: A weakly adsorbed polymer quenches the equilibrium nanocluster size and provides steric stabilization.


Input: Nanocluster size is tuned from ~ 20 to ~ 40 nm by experimentally varying the final Au nanoparticle concentration and the polymer/Au ratio, along with the charge on the initial Au nanoparticle surface.

Au

Au

Au


Input: Upon biodegradation of the quencher, the nanoclusters reversibly and fully dissociate to individual ~ 5 nm primary particles.


Input: Equilibrium cluster size is predicted semiquantitatively with a free energy model that balances short-ranged depletion and van der Waals attractions with longer-ranged electrostatic repulsion, as a function of the Au and polymer concentrations.

Au


Input: The close spacings of the Au nanoparticles in the clusters produce strong NIR extinction over a broad range of wavelengths from 650 to 900 nm, which is of practical interest in biomedical imaging.

Au


Input: Porphyrin metabolisms in human skin commensal Propionibacterium acnes bacteria: potential application to monitor human radiation risk.

Porphyrin


Input: Propionibacterium acnes (P. acnes), a Gram-positive anaerobic bacterium, is a commensal organism in human skin.


Input: Like human cells, the bacteria produce porphyrins, which exhibit fluorescence properties and make bacteria visible with a Wood' s lamp.

porphyrins


Input: In this review, we compare the porphyrin biosynthesis in humans and P. acnes.

porphyrin


Input: Also, since P. acnes living on the surface of skin receive the same radiation exposure as humans, we envision that the changes in porphyrin profiles (the absorption spectra and/or metabolism) of P. acnes by radiation may mirror the response of human cells to radiation.

porphyrin


Input: The porphyrin profiles of P. acnes may be a more accurate reflection of radiation risk to the patient than other biodosimeters/biomarkers such as gene up-/down-regulation, which may be non-specific due to patient related factors such as autoimmune diseases.

porphyrin


Input: Lastly, we discuss the challenges and possible solutions for using the P. acnes response to predict the radiation risk.


Input: Collective proton dynamics at highly charged interfaces studied by ab initio metadynamics.


Input: Surface proton conduction is of utmost importance in biology, materials science, and electrochemistry; yet experimental findings of ultrafast proton transport at densely packed arrays of anionic surface groups have remained controversial and unexplained.


Input: We present an ab initio molecular dynamics study of proton dynamics at sulfonic-acid terminated surface groups.

sulfonic-acid


Input: Results furnish a highly efficient collective mechanism of hydronium ion translocations at a critical surface group separation of ~ 6. 5 A.

hydronium


Input: Orientational fluctuations of SG trigger hydrogen bond breaking that sets off the hydronium ion motion.

hydrogen

hydronium


Input: The activation free energy of this process is 0. 3 eV (+/- 0. 1 eV).


Input: The soliton-like nature of this mechanism is owed to the trigonal symmetry of sulfonate anions and exceptionally strong interfacial hydrogen bonding.

sulfonate

hydrogen


Input: These insights should stimulate surface conductance studies at SG monolayers with sulfonic acid groups, and they bolster efforts in designing proton conducting polymers conducive to fuel cell operation above ~ 100 degrees C.

sulfonic acid


Input: Synthesis of polystyrene/polysilsesquioxane core/shell composite particles via emulsion polymerization in the existence of poly (gamma-methacryloxypropyl trimethoxysilane) sol.

polystyrene

polysilsesquioxane

poly (gamma-methacryloxypropyl trimethoxysilane)


Input: Here, we synthesized the polystyrene/polysilsesquioxane (PS/PSQ) core/shell latex particles via emulsion polymerization, which behave as an amusing morphology.

polystyrene

polysilsesquioxane

PSQ


Input: First, the nanosized PSQ particles were prepared by the hydrolysis-condensation reaction of gamma-methacryloxypropyl trimethoxysilane (MPTS) in ethanol medium.

PSQ

gamma-methacryloxypropyl trimethoxysilane

MPTS

ethanol


Input: Subsequently, the as-obtained methacryloxypropylene functionalized PSQ (PMPTS) sol was directly added into the emulsion system of styrene (St) monomer, and PS/PSQ composite particles with core/shell structure were obtained through emulsion polymerization.

methacryloxypropylene

PSQ

PMPTS

styrene

PSQ


Input: We found that the structure of the composite particles can be affected by the synthesis parameters such as reaction time, content of PMPTS added in the reaction, amount of coemulsifier, and the pH value of emulsion system, which were systemically explored by transmission electron microscopy (TEM), scanning electron microscope (SEM), Fourier transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS), and thermogravimetric analysis (TGA) in this work.

PMPTS


Input: These results indicate that the PMPTS particles in the size of about 5 nm could first absorb onto the surface of PS latex particles so as to assemble in a strawberry-like morphology.

PMPTS


Input: The further coalescence among the PMPTS particles would result in a continuous PMPTS shell around the PS core.

PMPTS

PMPTS


Input: Moreover, the hollow PSQ capsules were prepared after extraction of the PS core by organic solvent, further confirming the core/shell structure of the as-synthesized PS/PMPTS particles.

PSQ

PMPTS


Input: Meanwhile, we also explored the application of the PS/PSQ core/shell particles as a new kind of Pickering emulsifier in the emulsion polymerization of St, and composite particles with complex patchy morphologies have been obtained finally under different ratios of styrene monomer to PS/PMPTS colloidal emulsifier.

PSQ

PMPTS


Input: Discovery of 4-phenyl-2-phenylaminopyridine based TNIK inhibitors.


Input: A series of compounds based on a 4-phenyl-2-phenylaminopyridine scaffold that are potent and selective inhibitors of Traf2-and Nck-interacting kinase (TNIK) activity are described.


Input: These compounds were used as tools to test the importance of TNIK kinase activity in signaling and proliferation in Wnt-activated colorectal cancer cells.


Input: The results indicate that pharmacological inhibition of TNIK kinase activity has minimal effects on either Wnt/TCF4/beta-catenin-driven transcription or viability.


Input: The findings suggest that the kinase activity of TNIK may be less important to Wnt signaling than other aspects of TNIK function, such as its putative role in stabilizing the TCF4/beta-catenin transcriptional complex.


Input: Korean red ginseng (Panax ginseng) prevents obesity by inhibiting angiogenesis in high fat diet-induced obese C57BL/6J mice.


Input: Adipose tissue growth and development are thought to be associated with angiogenesis and extracellular matrix remodeling.


Input: Because ginseng has been shown to inhibit angiogenesis and matrix metalloproteinase (MMP) activity, we hypothesized that adipose tissue growth and obesity can be regulated by Korean ginseng (Panax ginseng C. A. Meyer).


Input: Wild-type C57BL/6J mice were fed for 8 weeks with a low fat diet, a high fat diet (HFD), or HFD supplemented with 0. 5% or 5% Korean red ginseng extract.


Input: We measured body weight, adipose tissue mass, food intake, MMP activity, and the expression of genes involved in angiogenesis and MMPs.


Input: Administering ginseng to HFD-induced obese mice produced reductions in body weight and adipose tissue mass compared with untreated counterparts.


Input: Ginseng treatment decreased blood vessel density and MMP activity in adipose tissues.


Input: Ginseng also reduced mRNA levels of angiogenic factors (e. g., VEGF-A and FGF-2) and MMPs (e. g., MMP-2 and MMP-9), whereas it increased mRNA levels of angiogenic inhibitors (e. g., TSP-1, TIMP-1, and TIMP-2) in adipose tissues.


Input: These results demonstrate that ginseng effectively reduces adipose tissue mass and prevents obesity in diet-induced obese mice and that this process may be mediated in part through the anti-angiogenic actions of ginseng.


Input: Citalopram at the recommended human doses after long-term treatment is genotoxic for male germ cell.

Citalopram


Input: The present study was aimed to examine if multiple oral administration of citalopram, an antidepressant drug, has any genotoxic potential on germ cells of male mice.

citalopram


Input: Mice were treated with citalopram for 4 or 8 weeks at the doses of 6, 12 and 24 mg/kg/day and were sacrificed 24 h after the last dose.

citalopram


Input: Multiple exposures to 12 and 24 mg/kg/day citalopram significantly increased sperm DNA strand breaks (14. 0 and 16. 0, respectively, compared to the concurrent control of 6. 8 at week 4 and 15. 2 and 20. 7, respectively, compared to the concurrent control of 7. 2 at week 8) and aberrant primary spermatocytes (6. 6% and 7. 6%, respectively, compared to the control of 2. 8% at week 4 and 7. 4% and 8. 4%, respectively, compared to the control of 3. 2% at week 8) as well as oxidative DNA damage (2. 7 and 3. 1, respectively, compared to the control of 1. 6 at week 4 and 3. 3 and 3. 9, respectively, compared to the control of 1. 7 at week 8).

citalopram


Input: Overall, this study provides that citalopram at the recommended human doses after long-term treatment is genotoxic for mouse germ cells.

citalopram


Input: Thus, male patients receiving citalopram may stand at higher risk for abnormal reproductive outcomes, particularly in the reproductive ages.

citalopram


Input: Aberrant transcription of the LHCGR gene caused by a mutation in exon 6A leads to Leydig cell hypoplasia type II.


Input: The luteinizing hormone/chorionic gonadotropin receptor (LHCGR) is essential for normal male sex differentiation.


Input: Recently, the additional primate-specific exon 6A of the LHCGR was discovered and it was shown to act as regulatory element at the transcriptional level.


Input: Compound heterozygous mutations in exon 6A (c. 580 A > G) and exon 11 (c. 1244T > C) were identified in the LHCGR of a male 46, XY patient with genital malformation.


Input: Analysis revealed that mutation c. 580A > G in exon 6A affects the splicing pattern resulting in an increase of transcripts containing the internal variants of exon 6A prone to nonsense-mediated decay.


Input: In contrast, mutation c. 1244T > C results in an amino acid substitution (Ile415Thr), which abolishes signal transduction due to structural changes.

amino acid


Input: When inherited in a compound heterozygous fashion these mutations result in Leydig cell hypoplasia (LCH) type II.


Input: Thus this study provides proof that mutations causing aberrant transcription can impair receptor function and thereby be causative of LCH.


Input: New amide alkaloids from Piper longum.

amide alkaloids


Input: Bioassay-guided phytochemical investigation on Piper longum resulted in the isolation of two new compounds.


Input: By analyses of the MS, IR, UV, 1D and 2D NMR data, the two new compounds were identified as 3 beta, 4 alpha-dihydroxy-1-(3-phenylpropanoyl)-piperidine-2-one (1) and (2E, 4E, 14Z)-6-hydroxyl-N-isobutyleicosa-2, 4, 14-trienamide (2).

3 beta, 4 alpha-dihydroxy-1-(3-phenylpropanoyl)-piperidine-2-one

(2E, 4E, 14Z)-6-hydroxyl-N-isobutyleicosa-2, 4, 14-trienamide


Input: In vitro anti-HBV bioassay demonstrated compound 1 possessed remarkable activity suppressing the secretion of HBeAg in Hep G2. 2. 15 cell line, with an IC (50) value of 0. 21mM and SI value of 16. 4.


Input: pi-Extended isomeric and expanded porphyrins.

porphyrins


Input: The phenomenon of pi-extension has been widely applied to, and exploited within, the field porphyrin chemistry.

porphyrin


Input: The development of reliable synthetic routes to various useful starting materials has facilitated the underlying preparative work.


Input: The chemical resemblance between porphyrins and expanded and isomeric porphyrins, as well as the increasing accessibility of the requisite starting materials is giving birth to the hybrid field of pi-extended expanded and isomeric porphyrins.

porphyrins

porphyrins

porphyrins


Input: This tutorial review is intended to provide an overview of up-to-date published synthetic efforts and to summarize the effect of annulation on the properties of expanded and isomeric porphyrins.

porphyrins


Input: Human mesenchymal stem-cell behaviour on direct laser micropatterned electrospun scaffolds with hierarchical structures.


Input: Direct laser machining and electrospinning are utilized to obtain a bi-layered hybrid scaffold with hierarchical topographical features to mimic extracellular matrix-like microenvironment of cells.


Input: Adult bone marrow derived human mesenchymal stem cells (hMSCs) are cultured in vitro in these hybrid scaffolds, and cell orientation, proliferation, viability, and differentiation are evaluated.


Input: The results show that this novel hybrid scaffold not only supports cell growth like traditional scaffolds, but also elicits positive responses from the cells, like lineage commitment and alignment, which are essential features of future scaffolds.


Input: Polariton dynamics under strong light-molecule coupling.


Input: We present a comprehensive experimental study of the photophysical properties of a molecule-cavity system under strong coupling conditions, using steady-state and femtosecond time-resolved emission and absorption techniques to selectively excite the lower and upper polaritons as well as the reservoir of uncoupled molecules.


Input: Our results demonstrate the complex decay routes in such hybrid systems and that, contrary to expectations, the lower polariton is intrinsically long-lived.


Input: Event based analysis of chlorothalonil concentrations following application to managed turf.

chlorothalonil


Input: Chlorothalonil concentrations exceeding acute toxicity levels for certain organisms have been measured in surface water discharge events from managed turf watersheds.

Chlorothalonil


Input: The duration of exceedence and the timing of these events related to precipitation/runoff and time since application, however, have not been explored.


Input: Chlorothalonil concentrations were measured from discharge waters draining a managed turf watershed in Duluth, Minnesota, USA, between 2003 and 2009.

Chlorothalonil


Input: The median chlorothalonil concentration was 0. 58 micro g/L.

chlorothalonil


Input: Approximately 2% of all measured concentrations exceeded the 7. 6 micro g/L median lethal concentration (LC50) acute toxicity level for rainbow trout.


Input: One-twentieth the LC50 concentration, equivalent to the level of concern (0. 38 micro g/L) for endangered species, was exceeded 31% of the time during the present study.


Input: The concentrations that exceeded the LC50 threshold were associated with eight rainfall/runoff events.


Input: Low dose exposures are a more important biological concern than acute occurrences.


Input: Exceedence concentrations associated with acute effects were significantly (p < 0. 05) correlated to time since application and were measured only in the fall following extensive application.


Input: A conflict exists between the transportability of chlorothalonil as suggested by its chemical properties and the data collected in the present study.

chlorothalonil


Input: With respect to course-wide golf course application, avoiding application until after the major autumn rainfall period but before the first snow coverage is recommended to reduce occurrence of chlorothalonil concentrations that exceed toxic levels associated with acute and chronic levels of concern.

chlorothalonil


Input: Genotype imputation via matrix completion.


Input: Most current genotype imputation methods are model-based and computationally intensive, taking days to impute one chromosome pair on 1000 people.


Input: We describe an efficient genotype imputation method based on matrix completion.


Input: Our matrix completion method is implemented in MATLAB and tested on real data from HapMap 3, simulated pedigree data, and simulated low-coverage sequencing data derived from the 1000 Genomes Project.


Input: Compared with leading imputation programs, the matrix completion algorithm embodied in our program MENDEL-IMPUTE achieves comparable imputation accuracy while reducing run times significantly.


Input: Implementation in a lower-level language such as Fortran or C is apt to further improve computational efficiency.


Input: Design and synthesis of diazatricyclodecane agonists of the G-protein-coupled receptor 119.

diazatricyclodecane


Input: A series of GPR119 agonists based on a 2, 6-diazatricyclo [3. 3. 1. 1 ~ 3, 7 ~] decane ring system is described.

2, 6-diazatricyclo [3. 3. 1. 1 ~ 3, 7 ~] decane


Input: Also provided is a detailed account of the development of a multigram scale synthesis of the diazatricyclic ring system, which was achieved using a Hofmann-L o ffler-Freytag reaction as the key step.

diazatricyclic


Input: The basis for the use of this complex framework lies in an attempt to constrain one end of the molecule in the " agonist conformation " as was previously described for 3-oxa-7-aza-bicyclo [3. 3. 1] nonanes.

3-oxa-7-aza-bicyclo [3. 3. 1] nonanes


Input: Optimization of carbamate analogues of the diazatricylic compounds led to the identification of 32i as a potent agonist of the GPR119 receptor with low unbound human liver microsomal clearance.

carbamate

diazatricylic


Input: The use of an agonist response weighted ligand lipophilic efficiency (LLE) termed AgLLE is discussed along with the issues of applying efficiency measures to agonist programs.


Input: Ultimately, solubility limited absorption and poor exposure reduced further interest in these molecules.


Input: Functionalization of monodisperse iron oxide NPs and their properties as magnetically recoverable catalysts.

iron oxide


Input: Here we report the functionalization of monodisperse iron oxide nanoparticles (NPs) with commercially available functional acids containing multiple double bonds such as linolenic (LLA) and linoleic (LEA) acids or pyridine moieties such as 6-methylpyridine-2-carboxylic acid, isonicotinic acid, 3-hydroxypicolinic acid, and 6-(1-piperidinyl) pyridine-3-carboxlic acid (PPCA).

iron oxide

linolenic (LLA) and linoleic (LEA) acids

pyridine

6-methylpyridine-2-carboxylic acid

isonicotinic acid

3-hydroxypicolinic acid

6-(1-piperidinyl) pyridine-3-carboxlic acid

PPCA


Input: Both double bonds and pyridine groups can be reacted with noble metal compounds to form catalytically active species in the exterior of magnetic NPs, thus making them promising magnetically recoverable catalysts.


Input: We determined that both LLA and LEA stabilize magnetic iron oxide NPs, allowing the formation of pi-complexes with bis (acetonitrile) dichloropalladium (II) in the NP shells.

LLA

LEA

iron oxide

bis (acetonitrile) dichloropalladium (II)


Input: In both cases, this leads to the formation of NP aggregates because of interparticle complexation.


Input: In the case of pyridine-containing ligands, only PPCA with two N-containing rings is able to provide NP stabilization and functionalization whereas other pyridine-containing acids did now allow sufficient steric stabilization.

pyridine

PPCA

N

pyridine


Input: The interaction of PPCA-based particles with Pd acetate also leads to aggregation because of interparticle interactions, but the aggregates that are formed are much smaller.

PPCA

Pd acetate


Input: Nevertheless, the catalytic properties in the selective hydrogenation of dimethylethynylcarbinol (DMEC) to dimethylvinylcarbinol were the best for the catalyst based on LLA, demonstrating that the NP aggregates in all cases are penetrable for DMEC.

dimethylethynylcarbinol

DMEC

dimethylvinylcarbinol

LLA

DMEC


Input: Easy magnetic separation of this catalyst from the reaction solution makes it promising as a magnetically recoverable catalyst.


Input: 70-kDa heat shock cognate protein hsc70 mediates calmodulin-dependent nuclear import of the sex-determining factor SRY.


Input: We recently showed that the developmentally important family of SOX (SRY (sex determining region on the Y chromosome)-related high mobility group (HMG) box) proteins require the calcium-binding protein calmodulin (CaM) for optimal nuclear accumulation, with clinical mutations in SRY that specifically impair nuclear accumulation via this pathway resulting in XY sex reversal.

calcium


Input: However, the mechanism by which CaM facilitates nuclear accumulation is unknown.


Input: Here, we show, for the first time, that the 70-kDa heat shock cognate protein hsc70 plays a key role in CaM-dependent nuclear import of SRY.


Input: Using a reconstituted nuclear import assay, we show that antibodies to hsc70 significantly reduce nuclear accumulation of wild type SRY and mutant derivatives thereof that retain CaM-dependent nuclear import, with an increased rate of nuclear accumulation upon addition of both CaM and hsc70, in contrast to an SRY mutant derivative with impaired CaM binding.


Input: siRNA knockdown of hsc70 in intact cells showed similar results, indicating clear dependence upon hsc70 for CaM-dependent nuclear import.


Input: Analysis using the technique of fluorescence recovery after photobleaching indicated that hsc70 is required for the maximal rate of SRY nuclear import in living cells but has no impact upon SRY nuclear retention/nuclear dynamics.


Input: Finally, we demonstrate direct binding of hsc70 to the SRY. CaM complex, with immunoprecipitation experiments from cell extracts showing association of hsc70 with wild type SRY, but not with a mutant derivative with impaired CaM binding, dependent on Ca (2 +).

Ca (2 +)


Input: Our novel findings strongly implicate hsc70 in CaM-dependent nuclear import of SRY.


Input: Effect of multilayer structure on cyclic performance of Si/Fe anode electrode in lithium-ion secondary batteries.

Si

Fe

lithium


Input: A buffer-strengthened Si/Fe multilayer film, consisting of amorphous silicon layers and polycrystalline Fe layers, is investigated as the anode for Li-ion batteries.

Si

Fe

silicon

Fe

Li


Input: This film can achieve a stable cycle-life performance with a high capacity.


Input: Decreasing the thickness of the Fe layer can lead to a higher capacity, which is related to the fast transport of the Li ion, but the cyclic performance deteriorates with repeated cycling.

Fe

Li


Input: In contrast, increasing the thickness of the Fe buffer layers and the number of deposit stacks improves the cycle life with high reversibility.

Fe


Input: Because of the strain in the Si layers suppressed by the primary multilayer structure, the long-term strength is preserved and the substantial fracture toughness is enhanced by the increasing numbers of effective grain boundaries and interfacial layers.

Si


Input: In addition, we demonstrate that the Ti underlayer promotes the electrochemical properties in the Si/Fe multilayer for various Fe layer thicknesses because of the enhanced adhesion of the interfacial electrode and current collector.

Ti

Si

Fe

Fe


Input: The mechanically optimized Si/Fe multilayer films can have superior cycle-life performances and higher capacities.

Si

Fe


Input: Notably, the 16-bilayer deposited electrode exhibits an excellent capacity retention of ~ 95% with ~ 204 mAh g (-1) over 300 cycles at a 1 C rate.


Input: Control of CYP11B2/CYP11B1 expression ratio and consequences for the zonation of the adrenal cortex.


Input: Access of corticotropin to glucocorticoid synthesis in adrenocortical cells is provided by the expression of the ACTH receptor (MC2R).


Input: Activation of the MC2R increases stimulatory G-protein, adenylyl cyclase, and protein kinase A (PKA) activities.


Input: Furthermore, PKA phosphorylates transcription factors that have a stimulating effect on glucocorticoid synthesis.


Input: Sensitivity of adrenocortical cells to renin/angiotensin-2 is conferred by the expression of the inhibitory G-protein-linked angiotensin-2 type 1 receptor (AT1R) that additionally associates to the phospholipase C-activating G-protein q.


Input: The AT1R is connected to the adrenal potassium sensory system and regulates calcium influx as well as phospholipase C-beta (PLC-beta) and thus calmodulin kinase-dependent transcription of steroidogenic enzymes.

potassium

calcium


Input: While AT1R signaling suppresses the influence of corticotropin on the generation of cyclic adenosine monophosphate, the expression of the AT1R and its associated enzyme activities are under the control of glucocorticoids.

cyclic adenosine monophosphate


Input: Thus, dominance of one of the two signaling pathways is dependent on two factors: the extracellular concentration of their ligands and the products of their signaling pathways.


Input: These findings are in favor of the hypothesis that the centripetal blood flow through the adrenal gland builds up a glucocorticoid gradient creating a morphogenetic field along which adrenal cortical cells adopt different functional states, leading to the typical zonation of the adrenal cortex.


Input: Sulfonylureas have antifungal activity and are potent inhibitors of Candida albicans acetohydroxyacid synthase.

Sulfonylureas


Input: The sulfonylurea herbicides exert their activity by inhibiting plant acetohydroxyacid synthase (AHAS), the first enzyme in the branched-chain amino acid biosynthesis pathway.

sulfonylurea

amino acid


Input: It has previously been shown that if the gene for AHAS is deleted in Candida albicans, attenuation of virulence is achieved, suggesting AHAS as an antifungal drug target.


Input: Herein, we have cloned, expressed, and purified C. albicans AHAS and shown that several sulfonylureas are inhibitors of this enzyme and possess antifungal activity.

sulfonylureas


Input: The most potent of these compounds is ethyl 2-(N-((4-iodo-6-methoxypyrimidin-2-yl) carbamoyl) sulfamoyl) benzoate (10c), which has a K (i) value of 3. 8 nM for C. albicans AHAS and an MIC 9 0 of 0. 7 mu g/mL for this fungus in cell-based assays.

ethyl 2-(N-((4-iodo-6-methoxypyrimidin-2-yl) carbamoyl) sulfamoyl) benzoate


Input: For the sulfonylureas tested there was a strong correlation between inhibitory activity toward C. albicans AHAS and fungicidal activity, supporting the hypothesis that AHAS is the target for their inhibitory activity within the cell.

sulfonylureas


Input: Calcium-dependent ligand binding and G-protein signaling of family B GPCR parathyroid hormone 1 receptor purified in nanodiscs.

Calcium


Input: GPCRs mediate intracellular signaling upon external stimuli, making them ideal drug targets.


Input: However, little is known about their activation mechanisms due to the difficulty in purification.


Input: Here, we introduce a method to purify GPCRs in nanodiscs, which incorporates GPCRs into lipid bilayers immediately after membrane solubilization, followed by single-step purification.


Input: Using this approach, we purified a family B GPCR, parathyroid hormone 1 receptor (PTH1R), which regulates calcium and phosphate homeostasis and is a drug target for osteoporosis.

calcium

phosphate


Input: We demonstrated that the purified PTH1R in nanodiscs can bind to PTH (1-34) and activate G protein.


Input: We also observed that Ca (2 +) is a weak agonist of PTH1R, and Ca (2 +) in millimolar concentration can switch PTH (1-34) from an inverse agonist to an agonist.

Ca (2 +)

Ca (2 +)


Input: Hence, our results show that nanodiscs are a viable vehicle for GPCR purification, enabling studies of GPCRs under precise experimental conditions without interference from other cellular or membrane components.


Input: Isoliquiritigenin showed strong inhibitory effects towards multiple UDP-glucuronosyltransferase (UGT) isoform-catalyzed 4-methylumbelliferone (4-MU) glucuronidation.

Isoliquiritigenin

UDP


Input: Isoliquiritigenin, a herbal ingredient with chalcone structure, has been speculated to be able to inhibit one of the most drug-metabolizing enzymes (DMEs) UDP-glucuronosyltransferase (UGT).

Isoliquiritigenin

chalcone

UDP


Input: Therefore, the aim of the present study was to investigate the inhibition of isoliquiritigenin towards important UGT isoforms in the liver and intestine, including UGT1A1, 1A3, 1A6, 1A7, 1A8, 1A9 and 1A10.

isoliquiritigenin


Input: The recombinant UGT-catalyzed 4-methylumbelliferone (4-MU) glucuronidation was used as probe reactions.


Input: The results showed that 100 mu M of isoliquiritigenin inhibited the activity of UGT1A1, UGT1A3, UGT1A6, UGT1A7, UGT1A8, UGT1A9, and UGT1A10 by 95. 2%, 76. 1%, 78. 9%, 87. 2%, 67. 2%, 94. 8%, and 91. 7%, respectively.

isoliquiritigenin


Input: The data fitting using Dixon plot and Lineweaver-Burk plot showed that the inhibition of UGT1A1, UGT1A9 and UGT1A10 by isoliquiritigenin was all best fit to the competitive inhibition, and the second plot using the slopes from the Lineweaver-Burk plot versus isoliquiritigenin concentrations was used to calculate the inhibition kinetic parameter (K (i)) to be 0. 7 mu M, 0. 3 mu M, and 18. 3 mu M for UGT1A1, UGT1A9, and UGT1A10, respectively.

isoliquiritigenin

isoliquiritigenin


Input: All these results indicated the risk of clinical application of isoliquiritigenin on the drug-drug interaction and other possible diseases induced by the inhibition of isoliquiritigenin towards these UGT isoforms.

isoliquiritigenin

isoliquiritigenin


Input: Synthesis and structure-activity relationship of piperidine-derived non-urea soluble epoxide hydrolase inhibitors.

piperidine

urea

epoxide


Input: A series of potent amide non-urea inhibitors of soluble epoxide hydrolase (sEH) is disclosed.

amide

urea

epoxide


Input: The inhibition of soluble epoxide hydrolase leads to elevated levels of epoxyeicosatrienoic acids (EETs), and thus inhibitors of sEH represent one of a novel approach to the development of vasodilatory and anti-inflammatory drugs.

epoxide

epoxyeicosatrienoic acids

EETs


Input: Structure-activities studies guided optimization of a lead compound, identified through high-throughput screening, gave rise to sub-nanomolar inhibitors of human sEH with stability in human liver microsomal assay suitable for preclinical development.


Input: Catalytic properties of a bacterial acylating acetaldehyde dehydrogenase: evidence for several active oligomeric states and coenzyme A activation upon binding.

acetaldehyde


Input: Until the last decade, two unrelated aldehyde dehydrogenase (ALDH) superfamilies, i. e. the phosphorylating and non-phosphorylating superfamilies, were known to catalyze the oxidation of aldehydes to activated or non-activated acids.

aldehyde

aldehydes


Input: However, a third one was discovered by the crystal structure of a bifunctional enzyme 4-hydroxy-2-ketovalerate aldolase/acylating acetaldehyde dehydrogenase (DmpFG) from Pseudomonas sp. strain CF600 (Manjasetty et al., Proc. Natl. Acad. Sci. USA 100 (2003) 6992-6997).

acetaldehyde


Input: Indeed, DmpF exhibits a non-phosphorylating CoA-dependent ALDH activity, but is structurally related to the phosphorylating superfamily.

CoA


Input: In this study, we undertook the characterization of the catalytic and structural properties of MhpEF from Escherichia coli, an ortholog of DmpFG in which MhpF converts acetaldehyde, produced by the cleavage of 4-hydroxy-2-ketovalerate by MhpE, into acetyl-CoA.

acetaldehyde

acetyl-CoA


Input: The kinetic data obtained under steady-state and pre-steady-state conditions show that the aldehyde dehydrogenase, MhpF, is active as a monomer, a unique feature relative to the phosphorylating and non-phosphorylating ALDH superfamilies.

aldehyde


Input: Our results also reveal that the catalytic properties of MhpF are not dependent on its oligomeric state, supporting the hypothesis of a structurally and catalytically independent entity.


Input: Moreover, the transthioesterification is shown to be rate-limiting and, when compared with a chemical model, its catalytic efficiency is increased 10 (4)-fold.


Input: Therefore, CoA binding to MhpF increases its reactivity and optimizes its positioning relative to the thioacylenzyme intermediate, thus enabling the formation of an efficient deacylation complex.

CoA


Input: Age dependent differences in the regulation of hippocampal steroid hormones and receptor genes: relations to motivation and cognition in male rats.

steroid


Input: Estrogen and estrogenic functions are age-dependently involved in the modulation of learning, memory and mood in female humans and animals.

Estrogen


Input: However, the investigation of estrogenic effects in males has been largely neglected.


Input: Therefore, we investigated the hippocampal gene expression of estrogen receptors alpha and beta (ER alpha, beta) in 8-week-old, 12-week-old and 24-week-old male rats.

estrogen


Input: To control for possible interactions between the expression of the estrogen receptor genes and other learning-related steroid receptors, androgen receptors (AR), corticosterone-binding glucocorticoid receptors (GR) and mineralocorticoid receptors (MR) were also measured.

estrogen

steroid

androgen

corticosterone


Input: Furthermore, the concentrations of the ligands 17 beta-estradiol, testosterone and corticosterone were measured.

17 beta-estradiol

testosterone

corticosterone


Input: The spatial training was conducted in a hole-board.


Input: The 8-week-old rats exhibited higher levels of general activity and exploration during the training and performed best with respect to spatial learning and memory, whereas no difference was found between the 12-week-old and 24-week-old rats.


Input: The trained 8-week-old rats exhibited increased gene expression of ER alpha compared with the untrained rats in this age group as well as the trained 12-week-old and 24-week-old rats.


Input: The concentrations of estradiol and testosterone, however, were generally higher in the 24-week-old rats than in the 8-week-old and 12-week-old rats.

estradiol

testosterone


Input: The ER alpha mRNA concentrations correlated positively with behavior that indicate general learning motivation.


Input: These results suggest a specific role of ER alpha in the age-related differences in motivation and subsequent success in the task.


Input: Thus, estrogen and estrogenic functions may play a more prominent role in young male behavior and development than has been previously assumed.

estrogen


Input: Single cell gene expression profiling of cortical osteoblast lineage cells.


Input: In tissues with complex architectures such as bone, it is often difficult to purify and characterize specific cell types via molecular profiling.


Input: Single cell gene expression profiling is an emerging technology useful for characterizing transcriptional profiles of individual cells isolated from heterogeneous populations.


Input: In this study we describe a novel procedure for the isolation and characterization of gene expression profiles of single osteoblast lineage cells derived from cortical bone.


Input: Mixed populations of different cell types were isolated from adult long bones of C57BL/6J mice by enzymatic digestion, and subsequently subjected to FACS to purify and characterize osteoblast lineage cells via a selection strategy using antibodies against CD31, CD45, and alkaline phosphatase (AP), specific for mature osteoblasts.


Input: The purified individual osteoblast lineage cells were then profiled at the single cell level via nanofluidic PCR.


Input: This method permits robust gene expression profiling on single osteoblast lineage cells derived from mature bone, potentially from anatomically distinct sites.


Input: In conjunction with this technique, we have also shown that it is possible to carry out single cell profiling on cells purified from fixed and frozen bone samples without compromising the gene expression signal.


Input: The latter finding means the technique can be extended to biopsies of bone from diseased individuals.


Input: Our approach for single cell expression profiling provides a new dimension to the transcriptional profile of the primary osteoblast lineage population in vivo, and has the capacity to greatly expand our understanding of how these cells may function in vivo under normal and diseased states.


Input: Directional scrolling of SiGe/Si/Cr nanoribbon on Si (111) surfaces controlled by two-fold rotational symmetry underetching.

SiGe

Si

Cr

Si


Input: The controllable fabrication of self-scrolling SiGe/Si/Cr helical nanoribbons on Si (111) substrates is investigated.

SiGe

Si

Cr

Si


Input: The initial lateral etching profile of the Si (111) substrates shows a 2-fold rotational symmetry using 4% ammonia solution, which provides guidance for initial scrolling of one-end-fixed nanoribbons to form helical structures.

Si

ammonia


Input: The chirality of the SiGe/Si/Cr helices with isotropic Young' s moduli is governed by the anisotropic underetching in the initial stage, which can be precisely judged, as the orientation of the ribbon is predesigned.

SiGe

Si

Cr


Input: Furthermore, the helicity angle and radius of the formed helices are investigated by the lateral etching behavior and Cosserat curve theory of the Si (111) substrates, respectively, which are consistent with the experimental data.

Si


Input: The present work provides the scrolling rule of nanoribbons with an isotropic Young' s modulus and anisotropic underetching in the formation of micro-/nanohelices.


Input: Modulation of multidrug resistance in cancer cells by chelidonine and Chelidonium majus alkaloids.

chelidonine


Input: Cancer cells often develop multidrug resistance (MDR) which is a multidimensional problem involving several mechanisms and targets.


Input: This study demonstrates that chelidonine and an alkaloid extract from Chelidonium majus, which contains protoberberine and benzo [c] phenanthridine alkaloids, has the ability to overcome MDR of different cancer cell lines through interaction with ABC-transporters, CYP3A4 and GST, by induction of apoptosis, and cytotoxic effects.

chelidonine

protoberberine and benzo [c] phenanthridine alkaloids


Input: Chelidonine and the alkaloid extract inhibited P-gp/MDR1 activity in a concentration-dependent manner in Caco-2 and CEM/ADR5000 and reversed their doxorubicin resistance.

Chelidonine

doxorubicin


Input: In addition, chelidonine and the alkaloid extract inhibited the activity of the drug modifying enzymes CYP3A4 and GST in a dose-dependent manner.

chelidonine


Input: The alkaloids induced apoptosis in MDR cells which was accompanied by an activation of caspase-3,-8,-6/9, and phosphatidyl serine (PS) exposure.

phosphatidyl serine


Input: cDNA arrays were applied to identify differentially expressed genes after treatment with chelidonine and the alkaloid extract.

chelidonine


Input: The expression analysis identified a common set of regulated genes related to apoptosis, cell cycle, and drug metabolism.


Input: Treatment of Caco-2 cells with 50 mu g/ml alkaloid extract and 50 mu M chelidonine for up to 48 h resulted in a significant decrease in mRNA levels of P-gp/MDR1, MRP1, BCRP, CYP3A4, GST, and hPXR and in a significant increase in caspase-3 and caspase-8 mRNA.

chelidonine


Input: Thus, chelidonine is a promising model compound for overcoming MDR and for enhancing cytotoxicity of chemotherapeutics, especially against leukaemia cells.

chelidonine


Input: Its efficacy needs to be confirmed in animal models.


Input: Design, functionalization strategies and biomedical applications of targeted biodegradable/biocompatible polymer-based nanocarriers for drug delivery.


Input: Design and functionalization strategies for multifunctional nanocarriers (e. g., nanoparticles, micelles, polymersomes) based on biodegradable/biocompatible polymers intended to be employed for active targeting and drug delivery are reviewed.


Input: This review will focus on the nature of the polymers involved in the preparation of targeted nanocarriers, the synthesis methods to achieve the desired macromolecular architecture, the selected coupling strategy, the choice of the homing molecules (vitamins, hormones, peptides, proteins, etc.), as well as the various strategies to display them at the surface of nanocarriers.


Input: The resulting morphologies and the main colloidal features will be given as well as an overview of the biological activities, with a special focus on the main in vivo achievements.


Input: Characterization of arsenic resistant bacteria from arsenic rich groundwater of West Bengal, India.

arsenic

arsenic


Input: Sixty-four arsenic (As) resistant bacteria isolated from an arsenic rich groundwater sample of West Bengal were characterized to investigate their potential role in subsurface arsenic mobilization.

arsenic

As

arsenic

arsenic


Input: Among the isolated strains predominance of genera Agrobacterium/Rhizobium, Ochrobactrum and Achromobacter which could grow chemolitrophically and utilize arsenic as electron donor were detected.

arsenic


Input: Higher tolerance to As (3 +) [maximum tolerable concentration (MTC): >= 10 mM], As (5 +) (MTC: >= 100 mM) and other heavy metals like Cu (2 +), Cr (2 +), Ni (2 +) etc.

As (3 +)

As

Cu (2 +)

Cr (2 +)

Ni (2 +)


Input: (MTC: >= 10 mM), presence of arsenate reductase and siderophore was frequently observed among the isolates.

arsenate


Input: Ability to produce arsenite oxidase and phosphatase enzyme was detected in 50 and 34% of the isolates, respectively.

arsenite


Input: Although no direct correlation among taxonomic identity of bacterial strains and their metabolic abilities as mentioned above was apparent, several isolates affiliated to genera Ochrobactrum, Achromobacter and unclassified Rhizobiaceae members were found to be highly resistant to As (3 +) and As (5 +) and positive for all the test properties.

As (3 +)

As (5 +)


Input: Arsenate reductase activity was found to be conferred by arsC gene, which in many strains was coupled with arsenite efflux gene arsB as well.

Arsenate

arsenite


Input: Phylogenetic incongruence between the 16S rRNA and ars genes lineages indicated possible incidence of horizontal gene transfer for ars genes.


Input: Based on the results we propose that under the prevailing low nutrient condition inhabitant bacteria capable of using inorganic electron donors play a synergistic role wherein siderophores and phosphatase activities facilitate the release of sediment bound As (5 +), which is subsequently reduced by arsenate reductase resulting into the mobilization of As (3 +) in groundwater.

As (5 +)

arsenate

As (3 +)


Input: Phase 1 and phase 2 drug metabolism and bile acid production of HepaRG cells in a bioartificial liver in absence of dimethyl sulfoxide.

bile acid

dimethyl sulfoxide


Input: The human liver cell line HepaRG has been recognized as a promising source for in vitro testing of metabolism and toxicity of compounds.


Input: However, currently the hepatic differentiation of these cells relies on exposure to dimethylsulfoxide (DMSO), which, as a side effect, has a cytotoxic effect and represses an all-round hepatic functionality.

dimethylsulfoxide

DMSO


Input: The AMC-bioartificial liver (AMC-BAL) is a three-dimensional bioreactor that has previously been shown to upregulate various liver functions of cultured cells.


Input: We therefore cultured HepaRG cells in the AMC-BAL without DMSO and characterized the drug metabolism.

DMSO


Input: Within 14 days of culture, the HepaRG-AMC-BALs contained highly polarized viable liver-like tissue with heterogeneous expression of CYP3A4.


Input: We found a substantial metabolism of the tested substrates, ranging from 26% (UDP-glucuronosyltransferase 1A1), 47% (CYP3A4), to 240% (CYP2C9) of primary human hepatocytes.

UDP


Input: The CYP3A4 activity could be induced 2-fold by rifampicin, whereas CYP2C9 activity remained equally high.

rifampicin


Input: The HepaRG-AMC-BAL secreted bile acids at 43% the rate of primary human hepatocytes and demonstrated hydroxylation, conjugation, and transport of bile salts.

bile acids

bile salts


Input: Concluding, culturing HepaRG cells in the AMC-BAL yields substantial phase 1 and phase 2 drug metabolism, while maintaining high viability, rendering DMSO addition superfluous for the promotion of drug metabolism.

DMSO


Input: Therefore, AMC-BAL culturing makes the HepaRG cells more suitable for testing metabolism and toxicity of drugs.


Input: FRET-capture: a sensitive method for the detection of dynamic protein interactions.


Input: Caught in the act: The FRET-Capture approach exploits a bound solvatochromic fluorophore, 4-N, N-dimethylamino-1, 8-naphthalimide, as a FRET donor in both inter-and intramolecular energy transfer.

4-N, N-dimethylamino-1, 8-naphthalimide


Input: A unique feature of this method is the additional level of signal selectivity as the FRET signal is only turned on when the donor is specifically bound to the protein of interest, eliminating high background and false positive signals.


Input: 3, 14-Bis (p-nitrophenyl)-17, 17-dipentyltetrabenzo [a, c, g, i]-fluorene: a new fluorophore displaying both remarkable solvatochromism and crystalline-induced emission.

3, 14-Bis (p-nitrophenyl)-17, 17-dipentyltetrabenzo [a, c, g, i]-fluorene


Input: A series of 17, 17-dialkyl-3, 14-diaryltetrabenzofluorenes were efficiently prepared by using Suzuki-Miyaura cross-coupling reactions of the corresponding 3, 14-dibromo derivatives.

17, 17-dialkyl-3, 14-diaryltetrabenzofluorenes

3, 14-dibromo


Input: Studies of the unique fluorescence properties of these compounds showed that they display intense blue to yellow fluorescence with high quantum yields in the solution state and blue to orange fluorescence with moderate quantum yields in the solid state.


Input: In addition, the fluorescence wavelength of the bis (p-nitrophenyl) derivative is remarkably solvent-dependent in a manner that correlates with the solvent polarity parameter E (T) (30).

bis (p-nitrophenyl)


Input: The results of density function theory calculations suggest that the intramolecular charge-transfer character of the HOMO-LUMO transition is responsible for the large solvent effect.


Input: Moreover, addition of water to a tetrahydrofuran (THF) solution of this compound leads to quenching of the yellow fluorescence owing to an increase in the solvent polarity.

tetrahydrofuran

THF


Input: However, when the amount of water fraction exceeds 70%, a new fluorescence band appears at the same orange-red emission wavelength as that of the solid-state fluorescence.


Input: This observation suggests the occurrence of a crystallization-induced emission (CIE) phenomenon in highly aqueous THF.

THF


Input: Loading metal nanostructures on cotton fabrics as recyclable catalysts.


Input: Noble metal nanostructures of varying compositions and shapes are loaded on cotton fabrics.


Input: The fabric-supported metal nanostructures can function as effective catalysts for different liquid-phase catalytic reactions.


Input: They exhibit superior recyclability, with the catalytic activities remaining nearly unchanged even after ten cycles of catalytic reactions for all of the three tested reactions.


Input: Controlled Synthesis of Double-Wall a-FePO4 Nanotubes and their LIB Cathode Properties.


Input: Double-wall amorphous FePO4 nanotubes are prepared by an oil-phase chemical route.


Input: The inward diffusion of vacancies and outward diffusion of ions through passivation layers result in double-wall nanotubes with thin walls.


Input: Such a process can be extended to prepare hollow polydedral nanocrystals and hollow ellipsoids.


Input: The double-wall FePO4 nanotubes show interesting cathode performance in Li ion batteries.

Li


Input: High-throughput screening of substrate chemistry for embryonic stem cell attachment, expansion, and maintaining pluripotency.


Input: Appropriate surface attachment is essential for growing embryonic stem (ES) cells in an undifferentiated state.


Input: It is challenging to identify the optimal surface chemistry of the substrata for ES cell attachment and maintenance.


Input: Using a rapid, high-throughput polymerization and screening platform with a comprehensive library of 66 monomer-grafted membrane surfaces, the optimal substrate, N-[3-(dimethylamino) propyl] methacrylamide (DMAPMA) has been identified to support strong attachment, high expansion capacity, and long-term self-renewal of ES cells (up to 7 passages).

N-[3-(dimethylamino) propyl] methacrylamide

DMAPMA


Input: This monomer-based, chemically defined, scalable, sustainable, relatively inexpensive, covalently grafted, and controllable polymeric substrate provides a new opportunity to manipulate surface chemistry for pluripotent stem culture.


Input: Understanding the dark and light-enhanced bactericidal action of cationic conjugated polyelectrolytes and oligomers.


Input: A multiscale investigation was carried out to study the dark and light-enhanced bactericidal mechanisms of poly (phenylene ethynylene) (PPE)-based cationic conjugated polyelectrolytes (CPEs) and oligo-phenylene ethynylenes (OPEs).

poly (phenylene ethynylene)

PPE

oligo-phenylene ethynylenes

OPEs


Input: On the morphological scale, Gram-negative E. coli cells exposed to CPE and OPE compounds in the dark show damage to the cell envelope, plasma membrane, and in some cases the cytoplasm, while with UV-irradiation, E. coli sustained catastrophic damages to both the cell envelope and cytoplasm.

OPE


Input: In contrast, the Gram-positive S. epi bacteria appeared intact when exposed to CPE and OPE compounds in the dark but showed damages to the cell envelope with UV-irradiation.

OPE


Input: To better understand the molecular basis of CPE-and OPE-induced morphological changes and damages to bacteria, we investigated the effect of these compounds on model bacterial plasma membrane and bacterial proteins and plasmid DNA.

OPE


Input: Measurements of dark membrane perturbation activity of the CPEs and OPEs using model lipid membranes support a carpet or detergent-like mechanism by which the antimicrobial compounds induce membrane collapse and phase transitions.

OPEs


Input: Under UV-irradiation, E. coli bacteria exposed to CPEs and OPEs showed covalent modifications and damages to both cellular protein and plasmid DNA, likely through oxidative pathways mediated by singlet oxygen and subsequent reactive oxygen species sensitized by the CPE and OPE compounds.

OPEs

oxygen

oxygen

OPE


Input: Our finding thus show that the antimicrobial polymers and oligomers exert toxicity toward Gram-negative bacteria by disrupting the morphology and structures of cell envelope and cytoplasm, including cellular components such as proteins and DNA, while exert toxicity toward Gram-positive bacteria by binding to and disrupting just the cell wall.


Input: Unconventional growth mechanism for monolithic integration of III-V on silicon.

silicon


Input: The heterogeneous integration of III-V optoelectronic devices with Si electronic circuits is highly desirable because it will enable many otherwise unattainable capabilities.

Si


Input: However, direct growth of III-V thin film on silicon substrates has been very challenging because of large mismatches in lattice constants and thermal coefficients.

silicon


Input: Furthermore, the high epitaxial growth temperature is detrimental to transistor performance.


Input: Here, we present a detailed studies on a novel growth mode which yields a catalyst-free (Al, In) GaAs nanopillar laser on a silicon substrate by metal-organic chemical vapor deposition at the low temperature of 400 degrees C.

Al

In

GaAs

silicon


Input: We study the growth and misfit stress relaxation mechanism by cutting through the center of the InGaAs/GaAs nanopillars using focused ion beam and inspecting with high-resolution transmission electron microscopy.

InGaAs

GaAs


Input: The bulk material of the nanopillar is in pure wurtzite crystal phase, despite the 6% lattice mismatch with the substrate, with all stacking disorders well confined in the bottom-most transition region and terminated horizontally.

wurtzite


Input: Furthermore, InGaAs was found to be in direct contact with silicon, in agreement with the observed crystal orientation alignment and good electrical conduction across the interface.

InGaAs

silicon


Input: This is in sharp contrast to many III-V nanowires on silicon which are observed to stem from thin SiN (x), SiO (2), or SiO (2)/Si openings.

silicon

SiN (x)

SiO (2)

SiO (2)

Si


Input: In addition, GaAs was found to grow perfectly as a shell layer on In (0. 2) Ga (0. 8) As with an extraordinary thickness, which is 15 times greater than the theoretical thin-film critical thickness for a 1. 5% lattice mismatch.

GaAs

In (0. 2) Ga (0. 8) As


Input: This is attributed to the core-shell radial geometry allowing the outer layers to expand and release the strain due to lattice mismatch.


Input: The findings in this study redefine the rules for lattice-mismatched growth on heterogeneous substrates and device structure design.


Input: A comparative study of the rotational dynamics of PF6 (-) anions in the crystals and liquid states of 1-butyl-3-methylimidazolium hexafluorophosphate: results from 31P NMR spectroscopy.

PF6 (-)

1-butyl-3-methylimidazolium hexafluorophosphate


Input: The rotational dynamics of the hexafluorophosphate anion (PF (6) (-)) in the crystalline and liquid states of the archetypal room temperature ionic liquid (RTIL) 1-butyl-3-methylimidazolium hexafluorophosphate ([C (4) mim] PF (6)) are investigated using (31) P NMR spectroscopy line shape analyses and spin-lattice relaxation time measurements.

hexafluorophosphate

PF (6) (-)

1-butyl-3-methylimidazolium hexafluorophosphate

[C (4) mim] PF (6)

(31) P


Input: The PF (6) (-) anion performs isotropic rotation in all three polymorphic crystals phases alpha, beta, and gamma as well as in the liquid state with a characteristic time scale that ranges from a few ps to a few hundred ps over a temperature range of 180-280 K.

PF (6) (-)


Input: The rotational correlation time tau (c) for PF (6) (-) rotation follows the sequence gamma-phase < alpha-phase =~ liquid < beta-phase.

PF (6) (-)


Input: On the other hand, in the liquid state, all local motions in the cation as well as its global rotational reorientation are characterized by time scales that are slower compared to that for the PF (6) (-) anion rotation.

PF (6) (-)


Input: The time scale tau (c) and the activation energy of PF (6) (-) rotation in this RTIL are found to be comparable with those observed in ordinary alkali and ammonium salts despite the large counterion size and low melting point of the former.

PF (6) (-)

ammonium salts


Input: The high sphericity of the PF (6) (-) ion is hypothesized to play an important role in the decoupling of its rotational dynamics that appear to be practically independent of the averaged cation-anion interaction.

PF (6) (-)


Input: Multiphoton imaging reveals a new leukocyte recruitment paradigm in the glomerulus.


Input: In contrast with many capillary beds, the glomerulus readily supports leukocyte recruitment.


Input: However, little is known regarding the actions of leukocytes following their recruitment to glomeruli.


Input: We used multiphoton confocal microscopy to examine leukocyte behavior in the glomerular microvasculature.


Input: In normal glomeruli, neutrophils and monocytes were retained in capillaries for several minutes, remaining static or migrating intravascularly.


Input: Induction of glomerular inflammation resulted in an increase in the duration of retention of static and migratory leukocytes.


Input: In response to immune complex deposition, both static and migratory neutrophils generated oxidants in inflamed glomeruli via a Mac-1-dependent mechanism.


Input: Our results describe a new paradigm for glomerular inflammation, suggesting that the major effect of acute inflammation is to increase the duration of leukocyte retention in the glomerulus.


Input: Moreover, these findings describe a previously unknown form of multicellular intravascular patrolling that involves both monocytes and neutrophils, which may underlie the susceptibility of the glomerulus to inflammation.


Input: Complementary detection of embryotoxic properties of substances in the neural and cardiac embryonic stem cell tests.


Input: In developmental toxicity testing, in vitro screening assays are highly needed to increase efficiency and to reduce animal use.


Input: A promising in vitro assay is the cardiac embryonic stem cell test (ESTc), in which the effect of developmental toxicants on cardiomyocyte differentiation is assessed.


Input: Recently, we developed a neural differentiation variant of the stem cell test (neural embryonic stem cell test [ESTn]).


Input: In both of these models, we have previously performed a series of transcriptomic studies to characterize gene expression changes (1) across time during normal differentiation and (2) in response to a series of developmental toxicants in the ESTn and ESTc.


Input: Here, using the cumulative of these studies, we compared gene expression profiles of ESTn and ESTc over time as well as model-specific changes induced by seven compounds, comprising six known in vivo developmental toxicants and one negative control.


Input: Time-related gene expression profiles showed similarities between the two EST systems.


Input: However, specific genes could be identified changing over time differently in each model related to the two different lineages of differentiation.


Input: Interestingly, compound-induced gene expression changes were generally model specific, especially for methylmercury and flusilazole, which were predicted better in ESTn and ESTc, respectively.

methylmercury

flusilazole


Input: Valproic acid-induced gene expression changes were most comparable out of the six developmental toxicants between the ESTn and ESTc.

Valproic acid


Input: Direct transcriptomic comparisons between the ESTn and ESTc indicate that combined transcriptomic analyses support and complement each other.


Input: Therefore, a combined approach incorporating ESTc and ESTn may improve developmental toxicant detection over individual assays.


Input: General methodology of using oil-in-water and water-in-oil emulsions for coiling nanofilaments.


Input: Hydrophobic carbon nanotubes (CNTs) and hydrophilic nanofilaments such as oxidized CNTs, Pd nanowires (NWs), and MnO (2) NWs are transformed from wires to rings by a general methodology.

carbon

Pd

MnO (2)


Input: We show that both oil-in-water and water-in-oil emulsions, so long as their droplet size is sufficiently small, can exert significant force to the entrapped nanostructures, causing their deformation.


Input: This effect can be easily achieved by simply mixing a few solutions in correct ratios.


Input: Even preformed oil droplets can take in CNTs from the aqueous solution converting them into rings, indicating the important role of thermodynamics: The question here is not if the droplets can exert sufficient force to bend the nanofilaments, because their random vibration may be already doing it.


Input: As long as the difference in solvation energy is large enough for a nanofilament, it would " want " to move away from the bulk solution and fit inside tiny droplets, even at the cost of induced strain energy.


Input: That said, the specific interactions between a droplet and a filament are also of importance.


Input: For example, when an oil droplet rapidly shrinks in size, it can compress the entrapped CNTs in multiple stages into structures with higher curvatures (thus higher strain) than that of a circular ring, which has minimal induced strain inside a spherical droplet.


Input: Preparation of raspberry-like polymer particles by a heterocoagulation technique utilizing hydrogen bonding interactions between steric stabilizers.

hydrogen


Input: Large polystyrene particles stabilized by poly (acrylic acid) (PAA) (L-PS (PAA)) (as the core) and small polystyrene particles stabilized by poly (vinyl pyrrolidone) (PVP) (S-PS (PVP)) (as the corona) were successfully used to prepare raspberry-like particles by a heterocoagulation technique utilizing the hydrogen bonding interaction between PAA and PVP.

polystyrene

poly (acrylic acid)

PAA

PS (PAA)

polystyrene

poly (vinyl pyrrolidone)

PVP

PS (PVP)

hydrogen

PAA

PVP


Input: The coverage of L-PS (PAA) by S-PS (PVP) could be controlled by adding PVP homopolymer to the L-PS (PAA) dispersion and by changing the molecular weight of the stabilizers.

PS (PAA)

PS (PVP)

PVP

PS (PAA)


Input: Moreover, the heterocoagulation of large poly (methyl methacrylate) particles stabilized by PAA (L-PMMA (PAA)) and S-PS (PVP) particles was also accomplished, resulting in the formation of L-PMMA (PAA)-core/S-PS (PVP)-corona raspberry-like composite particles.

poly (methyl methacrylate)

PAA

PMMA (PAA)

PS (PVP)

PMMA (PAA)

PS (PVP)


Input: These results suggested that the raspberry-like particles composed of various polymer particles could be formed by the heterocoagulation technique utilizing the hydrogen bonding interaction.

hydrogen


Input: Generation of B-doped graphene nanoplatelets using a solution process and their supercapacitor applications.

B-doped graphene


Input: Chemically modified graphene (CMG) nanoplatelets have shown great promise in various applications due to their electrical properties and high surface area.

graphene


Input: Chemical doping is one of the most effective methods to tune the electronic properties of graphene materials.

graphene


Input: In this work, novel B-doped nanoplatelets (borane-reduced graphene oxide, B-rG-O) were produced on a large scale via the reduction of graphene oxide by a borane-tetrahydrofuran adduct under reflux, and their use for supercapacitor electrodes was studied.

B

borane

graphene oxide

B

O

graphene oxide

borane

tetrahydrofuran


Input: This is the first report on the production of B-doped graphene nanoplatelets from a solution process and on the use of B-doped graphene materials in supercapacitors.

B-doped graphene

B-doped graphene


Input: The B-rG-O had a high specific surface area of 466 m (2)/g and showed excellent supercapacitor performance including a high specific capacitance of 200 F/g in aqueous electrolyte as well as superior surface area-normalized capacitance to typical carbon-based supercapacitor materials and good stability after 4500 cycles.

B

O

carbon


Input: Two-and three-electrode cell measurements showed that energy storage in the B-rG-O supercapacitors was contributed by ion adsorption on the surface of the nanoplatelets in addition to electrochemical redox reactions.

B

O


Input: Unique aggregation behavior of a carboxylate gemini surfactant with a long rigid spacer in aqueous solution.

carboxylate


Input: A new gemini surfactant with a long and rigid spacer, O, O'-bis (sodium 2-dodecylcarboxylate)-p-dibenzenediol (referred to as C (12) phi (2) C (12)), has been synthesized.

O, O'-bis (sodium 2-dodecylcarboxylate)-p-dibenzenediol

C (12) phi (2) C (12)


Input: Its aggregation in aqueous solution has been studied using static and dynamic light scattering measurements.


Input: The homologue O, O'-bis (sodium 2-dodecylcarboxylate)-p-benzenediol (C (12) phi C (12)) whose spacer only contains a single phenyl group was also examined for comparison.

O, O'-bis (sodium 2-dodecylcarboxylate)-p-benzenediol

C (12) phi C (12)

phenyl


Input: Dynamic light scattering (DLS) revealed the unexpected existence of large aggregates in the solution of C (12) phi (2) C (12).

C (12) phi (2) C (12)


Input: However, C (12) phi C (12) showed rather normal aggregation behavior.

C (12) phi C (12)


Input: Both the results of intrinsic viscosity and light scattering demonstrated a loose structure for the large aggregates of C (12) phi (2) C (12).

C (12) phi (2) C (12)


Input: This behavior was attributed to an extending configuration of C (12) phi (2) C (12) with the two alkyl tails stretching toward the solution due to the rigidity of the long spacer.

C (12) phi (2) C (12)

alkyl


Input: The large network-like aggregate formation was an inevitable outcome of spontaneously reducing the energy of the system.


Input: Freeze-fracture transmission electron microscopy (FF-TEM) images and (1) H NMR measurements supported this speculation.

(1) H


Input: Due to the columnar-like molecular geometry, the large network-like aggregates were directly transformed into rodlike micelles with increasing surfactant concentration.


Input: Depending on further micellar growth, the wormlike micelles were finally formed as confirmed by rheological measurements.


Input: Contrasting toxicokinetic evaluations and interspecies pharmacokinetic scaling approaches for small molecules and biologics: applicability to biosimilar development.


Input: 1. A 2-fold threshold typically used for prediction accuracy of interspecies scaling of clearance (CL) may be too liberal when using pharmacokinetic similarity in animals to advance biosimilar candidate selection for clinical testing.


Input: The purpose of this review is to identify interspecies scaling methods for use in de-risking biosimilar development prior to clinical testing.


Input: 2. Scaling approaches for predicting macromolecule CL were identified through literature review.


Input: Reports that evaluated predicted and observed human CLs for >= 5 individual compounds were considered.


Input: Absolute average fold-error (AAFE) was calculated for each method along with the proportion of compounds with individual fold-error values within a tighter threshold of 0. 7-1. 3.


Input: 3. Traditional simple allometry with a minimum of three species and the rule of exponents performed inconsistently with some groups of compounds resulting in a greater than 2-fold error (i. e. AAFE > 2).


Input: For monoclonal antibodies (mAbs), simplified allometric approaches employing a single species (monkey) with a fixed exponent of 0. 85 consistently resulted in lower AAFEs and a higher proportion of compounds within the tighter range of 0. 7-1. 3.


Input: 4. For macromolecules, and particularly mAbs, employing single-species monkey " simplified " allometric approaches with a fixed exponent of 0. 85 may be more appropriate than traditional allometric approaches.


Input: Peptide/protein separation with cationic polymer brush nanosponges for MALDI-MS analysis.


Input: A cationic polymer nanobrush was synthesized, attached to a MALDI target, and used for the fractionation of peptides and proteins based on their pI, prior to analysis by MALDI-MS.


Input: The cationic polymer nanobrush was synthesized on a gold substrate by AIBN photoinitiated polymerization, using a 70: 30 ratio of 2-aminoethyl methacrylate hydrochloride (AEMA): N-isopropylacrylamide (NIPAAM).

AIBN

2-aminoethyl methacrylate hydrochloride

AEMA

N-isopropylacrylamide

NIPAAM


Input: This brush showed selectivity for adsorption of acidic peptides and proteins and allowed fractionation of simple two-component mixtures to be completed in less than 10 min.


Input: The brush-adsorbed biomolecules were recovered by treating the nanobrush with ammonium hydroxide, which effectively collapsed the brush, thereby releasing the trapped compounds for MALDI MS analysis.

ammonium hydroxide


Input: These results demonstrate that nanobrush can serve as a convenient platform for rapid fractionation of biomolecules prior to analysis by MALDI-MS.


Input: Direct measurement of Dirac point energy at the graphene/oxide interface.

graphene

oxide


Input: We report the direct measurement of the Dirac point, the Fermi level, and the work function of graphene by performing internal photoemission measurements on a graphene/SiO (2)/Si structure with a unique optical-cavity enhanced test structure.

graphene

graphene

SiO (2)

Si


Input: A complete electronic band alignment at the graphene/SiO (2)/Si interfaces is accurately established.

graphene

SiO (2)

Si


Input: The observation of enhanced photoemission from a one-atom thick graphene layer was possible by taking advantage of the constructive optical interference in the SiO (2) cavity.

graphene

SiO (2)


Input: The photoemission yield was found to follow the well-known linear density-of-states dispersion in the vicinity of the Dirac point.


Input: At the flat band condition, the Fermi level was extracted and found to reside 3. 3 eV +/- 0. 05 eV below the bottom of the SiO (2) conduction band.

SiO (2)


Input: When combined with the shift of the Fermi level from the Dirac point, we are able to ascertain the position of the Dirac point at 3. 6 eV +/- 0. 05 eV with respect to the bottom of the SiO (2) conduction band edge, yielding a work function of 4. 5 eV +/- 0. 05 eV which is in an excellent agreement with theory.

SiO (2)


Input: The accurate determination of the work function of graphene is of significant importance to the engineering of graphene-based devices, and the measurement technique we have advanced in this Letter will have significant impact on numerous applications for emerging graphene-like 2-dimensional material systems.

graphene

graphene

graphene


Input: Sheehan' s syndrome.


Input: Sheehan' s syndrome (SS) is characterized by various degrees of hypopituitarism, and develops as a result of ischemic pituitary necrosis due to severe postpartum hemorrhage.


Input: Increased pituitary volume, small sella size, disseminated intravascular coagulation and autoimmunity are the proposed factors in the pathogenesis of SS.


Input: Hormonal insufficiencies, ranging from single pituitary hormone insufficiency to total hypopituitarism, are observed in patients.


Input: The fi rst most important issue in the diagnosis is being aware of the syndrome.


Input: Lack of lactation and failure of menstrual resumption after delivery that complicated with severe hemorrhage are the most important clues in diagnosing SS.


Input: The most frequent endocrine disorders are the deficiencies of growth hormone and prolactin.


Input: In patients with typical obstetric history, prolactin response to TRH seems to be the most sensitive screening test in diagnosing SS.


Input: Other than typical pituitary deficiency, symptoms such as anemia, pancytopenia, osteoporosis, impairment in cognitive functions and impairment in the quality of life are also present in these patients.


Input: Treatment of SS is based on the appropriate replacement of deficient hormones.


Input: Growth hormone replacement has been found to have positive effects; however, risk to benefit ratio, side effects and cost of the treatment should be taken into account.


Input: A dimeric form of N-methoxycarbonyl-2-amino-1, 8-naphthyridine bound to the A-A mismatch in the CAG/CAG base triad in dsRNA.

N-methoxycarbonyl-2-amino-1, 8-naphthyridine


Input: A dimeric form of N-methoxycarbonyl-2-amino-1, 8-naphthyridine (MCND) connected at the C2 position with a three-atom linker was examined for the binding to mismatches in double stranded RNA.

N-methoxycarbonyl-2-amino-1, 8-naphthyridine

MCND


Input: Despite the fully complementary hydrogen bonding groups to guanine, MCND did not bind to guanine-guanine mismatch but did to adenine-adenine mismatch.

hydrogen

guanine

MCND

guanine

guanine

adenine

adenine


Input: The base pairs flanking the mismatch had weak effect on the binding, with showing the strongest binding to the A-A mismatch in the CAG/CAG sequence.


Input: The A-A mismatch in the GAC/GAC sequence was a poor substrate for the MCND binding.

MCND


Input: A monomeric derivative of MCND and another derivative lacking a methylcarbamate group showed negligilble binding to the A-A mismatch and the sequence selectivity.

MCND

methylcarbamate