Input: These results are important clues for the better molecular design of RNA binding small molecules.


Input: Naphthyridinone (NTD) integrase inhibitors: N1 protio and methyl combination substituent effects with C3 amide groups.

Naphthyridinone

NTD

methyl

amide


Input: Substituent effects of a series of N1 protio and methyl naphthyridinone HIV-1 integrase strand-transfer inhibitors has been explored.

methyl naphthyridinone


Input: The effects of combinations of the N1 substituent and C3 amide groups was extensively studied to compare enzyme inhibition, antiviral activity and protein binding effects on potency.

amide


Input: The impact of substitution on ligand efficiency was considered and several compounds were advanced into in vivo pharmacokinetic studies ultimately leading to the clinical candidate GSK364735.


Input: Overexpression of Escherichia coli nucleotide excision repair genes after cisplatin-induced damage.

nucleotide

cisplatin


Input: Cisplatin is currently used in tumor chemotherapy to induce the death of malignant cells through blockage of DNA replication.

Cisplatin


Input: It is a commonly used chemotherapeutic agent binding mono-or bifunctionally to guanines in DNA.

guanines


Input: Escherichia coli K12 mutant strains deficient in nucleotide excision repair (NER) were submitted to increasing concentrations of cisplatin, and the results revealed that uvrA and uvrB mutants are sensitive to this agent, while uvrC and cho mutants remain as the wild type strain.

nucleotide

cisplatin


Input: The time required for both gene expression turn-off and return to normal weight DNA in wild-type E. coli was not accomplished even after 4 h post-treatment with cisplatin, while the same process takes place within 1. 5 h after ultraviolet radiation (UV).

cisplatin


Input: Besides, a heavily damaging action of cisplatin can be seen not only by persistent nicks on genomic DNA, but also by NER gene expression exceeding manifold that seen after equivalent lethal doses of UV.

cisplatin


Input: Moreover, cisplatin caused an increase in uvrB gene expression from its putative upstream promoter P3 in an SOS-independent manner.

cisplatin


Input: Cockayne syndrome b maintains neural precursor function.


Input: Neurodevelopmental defects are observed in the hereditary disorder Cockayne syndrome (CS).


Input: The gene most frequently mutated in CS, Cockayne Syndrome B (CSB), is required for the repair of bulky DNA adducts in transcribed genes during transcription-coupled nucleotide excision repair.


Input: CSB also plays a role in chromatin remodeling and mitochondrial function.


Input: The role of CSB in neural development is poorly understood.


Input: Here we report that the abundance of neural progenitors is normal in Csb (-/-) mice and the frequency of apoptotic cells in the neurogenic niche of the adult subependymal zone is similar in Csb (-/-) and wild type mice.


Input: Both embryonic and adult Csb (-/-) neural precursors exhibited defective self-renewal in the neurosphere assay.


Input: In Csb (-/-) neural precursors, self-renewal progressively decreased in serially passaged neurospheres.


Input: The data also indicate that Csb and the nucleotide excision repair protein Xpa preserve embryonic neural stem cell self-renewal after UV DNA damage.


Input: Although Csb (-/-) neural precursors do not exhibit altered neuronal lineage commitment after low-dose UV (1J/m (2)) in vitro, neurons differentiated in vitro from Csb (-/-) neural precursors that had been irradiated with 1J/m (2) UV exhibited defective neurite outgrowth.


Input: These findings identify a function for Csb in neural precursors.


Input: Spp1, a member of the Set1 Complex, promotes meiotic DSB formation in promoters by tethering histone H3K4 methylation sites to chromosome axes.


Input: Meiotic chromosomes are organized into arrays of loops that are anchored to the chromosome axis structure.


Input: Programmed DNA double-strand breaks (DSBs) that initiate meiotic recombination, catalyzed by Spo11 and accessory DSB proteins, form in loop sequences in promoters, whereas the DSB proteins are located on chromosome axes.


Input: Mechanisms bridging these two chromosomal regions for DSB formation have remained elusive.


Input: Here we show that Spp1, a conserved member of the histone H3K4 methyltransferase Set1 complex, is required for normal levels of DSB formation and is associated with chromosome axes during meiosis, where it physically interacts with the Mer2 DSB protein.


Input: The PHD finger module of Spp1, which reads H3K4 methylation close to promoters, promotes DSB formation by tethering these regions to chromosome axes and activating cleavage by the DSB proteins.


Input: This paper provides the molecular mechanism linking DSB sequences to chromosome axes and explains why H3K4 methylation is important for meiotic recombination.


Input: Spontaneous renal tumors in two rats from a thirteen week rodent feeding study with grain from molecular stacked trait lepidopteran and coleopteran resistant (DP-O O 4114-3) maize.


Input: A thirteen week feeding study was conducted by feeding young adult male and female Sprague Dawley [Crl: CD (R) (SD)] rats diets containing grain from genetically modified (GM) DP-O O 4114-3 maize that was either untreated (4114) or treated in the field with glufosinate ammonium (4114GLU).

glufosinate ammonium


Input: Control rats were fed diets containing the same concentration of near isogenic, non-GM maize grain (091) or one of three types of commercially available non-GM maize grain.


Input: At the end of the in-life phase, renal tubule tumors were reported in two male rats consuming diets containing 4114 maize grain.


Input: An expert panel of pathologists was convened as a Pathology Working Group (PWG) to review coded kidney histology sections from control (091) and treated (4114 and 4114GLU) male rats.


Input: The objectives were for the panel to characterize the histopathologic findings and to interpret their relationship to consumption of the indicated diet.


Input: The PWG concluded unanimously that the kidney tumors were characteristic of amphophilic-vacuolar (AV) tumors and AV atypical tubular hyperplasia which represent a distinctive phenotype that has been reported to occur sporadically in young Sprague Dawley Rats.


Input: The PWG determined that the neoplasms and atypical tubular hyperplasias were multicentric and bilateral which typifies tumors of familial origin.


Input: Degenerative/regenerative or cytotoxic changes consistent with nephrotoxicity leading to tumor induction were not observed in these rats and thus supports the conclusion that tumors were unrelated to consumption of the test diet.


Input: It was the unanimous opinion of the PWG that the proliferative renal tubule cell lesions were spontaneous and not related to consumption of diets containing 4114 maize grain.


Input: Non-ionic Gd-based MRI contrast agents are optimal for encapsulation into phosphatidyldiglycerol-based thermosensitive liposomes.

Gd

phosphatidyldiglycerol


Input: Thermosensitive liposomes (TSL) with encapsulated magnetic resonance imaging (MRI) longitudinal relaxation time (T (1)) contrast agents (CAs) have been proposed for MRI assisted interventional thermotherapy in solid tumors.


Input: Here the feasibility of 6 clinically approved CAs (Gd-DTPA, Gd-BOPTA, Gd-DOTA, Gd-BT-DO3A, Gd-DTPA-BMA, and Gd-HP-DO3A) for formulation into TSL was investigated.

Gd-DTPA

Gd-BOPTA

Gd-DOTA

Gd-DTPA-BMA


Input: CAs were passively encapsulated with 323 mOs kg (-1) into 1, 2-dipalmitoyl-sn-glycero-3-phosphocholine/1, 2-distearoyl-sn-glycero-3-phosphocholine/1, 2-dipalmitoyl-sn-glycero-3-phosphodiglycerol 50/20/30 (mol/mol) TSL (DPPG (2)-TSL) to obtain stable formulations.

1, 2-dipalmitoyl-sn-glycero-3-phosphocholine

1, 2-distearoyl-sn-glycero-3-phosphocholine

1, 2-dipalmitoyl-sn-glycero-3-phosphodiglycerol

DPPG (2)


Input: T (1) relaxivity (r (1)) and diffusive permeability to water (P (d)) across the membrane were determined.


Input: Shelf life at 4 degrees C was investigated by determining lysolipid content up to 10 weeks after preparation.


Input: All preparations were monodispersed with comparable small vesicle sizes (~ 135 nm).


Input: Neither zeta potential nor phase transition temperature (T (m)) was affected by the CA.


Input: The formulations showed an increase in r (1) in the temperature range between 38 and 44 degrees C.


Input: This correlated with the phase transition.


Input: Change in r (1) (Delta r (1) = r (1) (45. 3 degrees C)-r (1) (37. 6 degrees C)) and r (1) (T < T (m)) depended on the encapsulated CA concentration.


Input: P (d) at T <= 37. 6 degrees C was lower for DPPG (2)-TSL encapsulating non-ionic Gd-BT-DO3A, Gd-DTPA-BMA, and Gd-HP-DO3A.


Input: All CAs except Gd-DTPA-BMA induced phospholipid hydrolysis, which resulted in unwanted CA leakage.


Input: The serum proteins HSA and IgG both contributed to the increase of MRI signal at 30 degrees C by increasing P (d).


Input: A high concentration of encapsulated CA is a prerequisite to achieve a sufficiently high Delta r (1) during heat triggered CA release combined with a low r (1) at 37 degrees C.


Input: Hence, the optimal CA is characterized by a non-ionic structure and a low contribution to osmolality.


Input: Wogonin inhibits H2O2-induced vascular permeability through suppressing the phosphorylation of caveolin-1.

Wogonin


Input: Wogonin, a naturally occurring monoflavonoid extracted from the root of Scutellaria baicalensis Georgi, has been reported for its anti-oxidant activity.

Wogonin

monoflavonoid


Input: However, it is still unclear whether wogonin can inhibit oxidant-induced vascular permeability.

wogonin


Input: In this study, we evaluated the effects of wogonin on H2O2-induced vascular permeability in human umbilical vein endothelial cells (HUVECs).

wogonin


Input: We found that wogonin can suppress the H2O2-stimulated actin remodeling and albumin uptake of HUVECs, as well as transendothelial cell migration of the human breast carcinoma cell MDA-MB-231.

wogonin


Input: The mechanism revealed that wogonin inhibited H2O2-induced phosphorylation of caveolin-1 (cav-1) associating with the suppression of stabilization of VE-cadherin and beta-catenin.

wogonin


Input: Moreover, wogonin repressed anisomycin-induced phosphorylation of p38, cav-1 and vascular permeability.

wogonin

anisomycin


Input: These results suggested that wogonin could inhibit H2O2-induced vascular permeability by downregulating the phosphorylation of cav-1, and that it might have a therapeutic potential for the diseases associated with the development of both oxidant and vascular permeability.

wogonin


Input: Inhibitory effect of Crotalus durissus terrificus venom on chronic edema induced by injection of bacillus Calmette-Gu e rin into the footpad of mice.


Input: In this study, we evaluated the effect of the Crotalus durissus terrificus (Cdt) venom on the chronic paw edema induced by the injection of bacillus Calmette-Gu e rin (BCG) into the footpad of mice.


Input: The BCG injection evoked chronic edema, which was significantly diminished in animals treated subcutaneously (s. c.) with Cdt venom 1 h before or after the BCG injection.


Input: This inhibition persisted throughout the evaluation period (15 days).


Input: In mice injected with Cdt venom 6 or 11 days after injection of BCG, we observed a significant reduction in edema only in the period after the venom injection.


Input: While studying possible mechanisms involved in this inhibition, we observed that pre-treatment with dexamethasone, zileuton or Boc2 (a selective antagonist of formyl peptide receptors), but not with indomethacin, canceled out the inhibitory effect of Cdt venom on the edema induced by BCG.

dexamethasone

zileuton

formyl

indomethacin


Input: These results strongly suggest that this rattlesnake venom can stimulate the generation of mediators from the lipoxygenase pathway, which can down-regulate this chronic inflammatory edema.


Input: Using fractionated venom, the results indicated that crotoxin was the only component of Cdt venom responsible for this inhibitory effect.


Input: These results indicated that crotoxin, the main toxin of the C. durissus terrificus venom, has a significant inhibitory effect on BCG-induced chronic edema, possibly by generating anti-inflammatory mediators from the lipoxygenase pathway.


Input: Evaluation of genotoxicity in leukocytes and testis following intra-vasal contraception with RISUG and its reversal by DMSO and NaHCO3 in Wistar albino rats.

DMSO


Input: Evaluation of genotoxicity of RISUG ((R))-a vas based contraceptive, was carried out in the present study.


Input: Animals were allotted into groups of sham operated control, vas occlusion with RISUG (5-7 mu l) for 360 days and reversal by DMSO (250-500 mu l) and 5% NaHCO3 (500 mu l).

DMSO


Input: Blood samples and testis were collected at 360 days of vas occlusion and 90 days of vas occlusion reversal for comet analysis.


Input: Hydrogen peroxide induced samples were used as positive control.

Hydrogen peroxide


Input: Olive moment, tail length and percentage DNA in tail were recorded with minimum variation in all groups for both leukocytes and testis.


Input: When compared with positive control the variation was highly significant for both 20 mu M and 50 mu M H2O2 (p < 0. 001).


Input: It is concluded that vas occlusion with RISUG at the contraceptive dose regimen is not associated with genotoxicity in leukocytes or the testis of pre-and post-reversal rats.


Input: Influence of developmental lead exposure on expression of DNA methyltransferases and methyl cytosine-binding proteins in hippocampus.

methyl cytosine


Input: Developmental exposure to lead (Pb) has adverse effects on cognitive functioning and behavior that can persist into adulthood.

Pb


Input: Exposures that occur during fetal or early life periods may produce changes in brain related to physiological re-programming from an epigenetic influence such as altered DNA methylation status.


Input: Since DNA methylation is regulated by DNA methyltransferases and methyl cytosine-binding proteins, this study assessed the extent to which developmental Pb exposure might affect expression of these proteins in the hippocampus.

methyl cytosine

Pb


Input: Long Evans dams were fed chow with or without added Pb acetate (0, 150, 375, 750 ppm) prior to breeding and remained on the same diet through weaning (perinatal exposure group).

Pb acetate


Input: Other animals were exposed to the same doses of Pb but exposure started on postnatal day 1 and continued through weaning (early postnatal exposure group).

Pb


Input: All animals were euthanized on day 55 and hippocampi were removed.


Input: Western blot analyses showed significant effects of Pb exposure on DNMT1, DNMT3a, and MeCP2 expression, with effects often seen at the lowest level of exposure and modified by sex and developmental window of Pb exposure.

Pb

Pb


Input: These data suggest potential epigenetic effects of developmental Pb exposure on DNA methylation mediated at least in part through dysregulation of methyltransferases.

Pb


Input: New formulation approaches to improve solubility and drug release from fixed dose combinations: Case examples pioglitazone/glimepiride and ezetimibe/simvastatin.

pioglitazone

glimepiride

ezetimibe

simvastatin


Input: Low aqueous solubility is often a limiting aspect to the bioavailability of poorly soluble, but highly permeable drugs (class II compounds according to the Biopharmaceutics Classification System-BCS) administered in single drug products or as fixed dose combinations.


Input: The aim of the present series of experiments was to improve the solubility and dissolution of two fixed dose combination formulations (FDC), each consisting of two BCS class II drugs.


Input: The first FDC contained a weak acid (glimepiride) and a weak base (pioglitazone), while the second FDC contained two compounds (simvastatin and ezetimibe) that are essentially non-ionised over the physiological pH range.

glimepiride

pioglitazone

simvastatin

ezetimibe


Input: The formulation approaches used were as follows: (a) an inclusion complex with hydroxypropyl-beta-cyclodextrin (HP-beta-CD), (b) a solid dispersion with Soluplus (R), a new highly water soluble polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer and (c) a ternary inclusion complex with both HP-beta-CD and Soluplus (R).

hydroxypropyl-beta-cyclodextrin

HP-beta-CD

Soluplus

polyvinyl caprolactam

polyvinyl acetate

polyethylene glycol

HP-beta-CD

Soluplus


Input: Solid state analysis was performed for the pure drugs, and all formulations using powder X-ray diffraction (PXRD).


Input: The in vitro performance of the different formulation approaches, as gauged by solubility and dissolution experiments, was compared with that of the marketed products containing the respective fixed dose combinations, Tandemact (R) 30mg/4mg tablets and Inegy (R) 10mg/40mg tablets.

Tandemact

Inegy


Input: The FDCs of the pure drugs and the marketed products showed very poor (and especially for pioglitazone, strongly pH-dependent) dissolution.

pioglitazone


Input: By contrast, all binary and ternary inclusion complexes showed enhanced release for both drugs in the FDC.


Input: The ternary inclusion complex generated synergistic improvement in solubility and dissolution results for both FDCs.


Input: For example, in pH conditions of the fasted small intestine after a test duration of 240min, we observed 100% dissolution of both drugs from the ternary pioglitazone/glimepiride (30mg/4mg) complex formulation, whereas from the marketed formulation less than 5% pioglitazone, and only 25% glimepiride dissolved.

pioglitazone

glimepiride

pioglitazone

glimepiride


Input: Using the same conditions, 60% ezetimibe and 85% simvastatin dissolved from the ternary ezetimibe/simvastatin (10mg/40mg) complex formulation, whereas with less than 5% ezetimibe and 10% simvastatin dissolved after 240min, the marketed FDC formulation showed poor dissolution.

ezetimibe

simvastatin

ezetimibe

simvastatin

ezetimibe

simvastatin


Input: Based on the results of the present study, the bioavailability of both drugs in the fixed dose combination is likely to be increased after oral administration of the new formulations, especially when the fixed dose combination is formulated as a ternary complex consisting of HP-beta-CD and Soluplus (R).

HP-beta-CD

Soluplus


Input: Preparation of highly porous gastroretentive metformin tablets using a sublimation method.

metformin


Input: The present investigation is aimed to formulate floating gastroretentive tablets containing metformin using a sublimation material.

metformin


Input: In this study, the release of the drug from a matrix tablet was highly dependent on the polymer concentrations.


Input: In all formulations, initial rapid drug release was observed, possibly due to the properties of the drug and polymer.


Input: The effect of the amount of PEO on swelling and eroding of the tablets was determined.

PEO


Input: The water-uptake and erosion behavior of the gastroretentive (GR) tablets were highly dependent on the amount of PEO.

PEO


Input: The water-uptake increased with increasing PEO concentration in the tablet matrix.

PEO


Input: The weight loss from tablets decreased with increasing amounts of PEO.

PEO


Input: Camphor was used as the sublimation material to prepare GR tablets that are low-density and easily floatable.

Camphor


Input: Camphor was changed to pores in the tablet during the sublimation process.

Camphor


Input: SEM revealed that the GR tablets have a highly porous morphology.


Input: Floating properties of tablets and tablet density were affected by the sublimation of camphor.

camphor


Input: Prepared floating gastroretentive tablets floated for over 24 h and had no floating lag time.


Input: However, as the amount of camphor in the tablet matrix increased, the crushing strength of the tablet decreased after sublimation.

camphor


Input: Release profiles of the drug from the GR tablets were not affected by tablet density or porosity.


Input: In pharmacokinetic studies, the mean plasma concentration of the GR tablets after oral administration was greater than the concentration of glucophase XR.


Input: Also, the mean AUC (0-infinity) values for the GR tablets were significantly greater than the plasma concentrations of glucophase XR.


Input: Comparative genomics, molecular evolution and computational modeling of ALDH1B1 and ALDH2.


Input: Vertebrate ALDH2 genes encode mitochondrial enzymes capable of metabolizing acetaldehyde and other biological aldehydes in the body.

acetaldehyde

aldehydes


Input: Mammalian ALDH1B1, another mitochondrial enzyme sharing 72% identity with ALDH2, is also capable of metabolizing acetaldehyde but has a tissue distribution and pattern of activity distinct from that of ALDH2.

acetaldehyde


Input: Bioinformatic analyses of several vertebrate genomes were undertaken using known ALDH2 and ALDH1B1 amino acid sequences.

amino acid


Input: Phylogenetic analysis of many representative vertebrate species (including fish, amphibians, birds and mammals) indicated the presence of ALDH1B1 in many mammalian species and in frogs (Xenopus tropicalis); no evidence was found for ALDH1B1 in the genomes of birds, reptiles or fish.


Input: Predicted vertebrate ALDH2 and ALDH1B1 subunit sequences and structures were highly conserved, including residues previously shown to be involved in catalysis and coenzyme binding for human ALDH2.


Input: Studies of ALDH1B1 sequences supported the hypothesis that the ALDH1B1 gene originated in early vertebrates from a retrotransposition of the vertebrate ALDH2 gene.


Input: Given the high degree of similarity between ALDH2 and ALDH1B1, it is surprising that individuals with an inactivating mutation in ALDH2 (ALDH2 * 2) do not exhibit a compensatory increase in ALDH1B1 activity.


Input: We hypothesized that the similarity between the two ALDHs would allow for dominant negative heterotetramerization between the inactive ALDH2 mutants and ALDH1B1.


Input: Computational-based molecular modeling studies examining predicted protein-protein interactions indicated that heterotetramerization between ALDH2 and ALDH1B1 subunits was highly probable and may partially explain a lack of compensation by ALDH1B1 in ALDH2 (*) 2 individuals.


Input: MolShaCS: a free and open source tool for ligand similarity identification based on Gaussian descriptors.


Input: Molecular similarity evaluation is an important step in most drug development strategies, since molecular similarity is usually related to functional similarity.


Input: Here, we developed a method based on the Gaussian description of molecular shape and charge distribution for molecular similarity identification.


Input: The method was evaluated using the Directory of Useful Decoys (DUD) and a retrospective test.


Input: Enrichment factors computed for DUD targets showed that the proposed method performs very well in recognizing molecules with similar physicochemical properties and dissimilar topologies, reaching an average AUC of 0. 63 and enrichment factor of 10 at 0. 5% of decoys.


Input: A retrospective test also showed that nine mineralocorticoid ligands were ranked among the top ten molecules in a search of a database of approved drugs for molecules similar to aldosterone.

aldosterone


Input: Altogether, these data show that the Gaussian-based description of molecular shape and charge distribution implemented in the program MolShaCS is an efficient method for molecular similarity identification.


Input: The program is publicly available at the address http://www. ifsc. usp. br/biotechmol.


Input: Colloids in Flatland: a perspective on 2D phase-separated systems, characterisation methods, and lineactant design.


Input: In 1861 Thomas Graham gave birth to a new field of science, today known as colloid science.


Input: Nowadays, the notion " colloid " is often used referring to systems consisting of two immiscible phases, one of which is finely dispersed into the other.


Input: Research on colloids deals mostly with sols (solids dispersed in a liquid), emulsions (liquids dispersed in liquid), and foams (gas dispersed in a liquid).


Input: Because the dispersed particles are small, there is a lot of interface per unit mass.


Input: Not surprisingly, therefore, the properties of the interface have often a decisive effect on the behaviour of colloids.


Input: Water-air interfaces have a special relevance in this field: many water-insoluble molecules can be spread on water and, given the right spreading conditions and enough available surface area, their spreading proceeds until a monolayer (a one-molecule thick layer) eventually remains.


Input: Several 2D phases have been identified for such monolayers, like " gas ", " liquid expanded ", " liquid condensed ", and " solid ".


Input: The central question of this review is whether these 2D phases can also exist as colloidal systems, and what stabilizes the dispersed state in such systems.


Input: We shall present several systems capable of yielding 2D phase separation, from those based on either natural or fluorinated amphiphiles, to polymer-based ones.


Input: We shall seek for analogies in 3D and we shall try to clarify if the lines between these 2D objects play a similar role as the interfaces between 3D colloidal systems.


Input: In particular, we shall consider the special role of molecules that tend to accumulate at the phase boundaries, that is, at the contact lines, which will therefore be denoted " line-actants " (molecules that adsorb at a 1D interface, separating two 2D colloidal entities), by analogy to the term " surfactant " (which indicates a molecule that adsorbs at a 2D interface separating two 3D colloidal entities).


Input: Observation of direct vibrational excitation in gas-surface collisions of CO with Au (111): a new model system for surface dynamics.

CO

Au


Input: We report vibrational excitation of CO from its ground (v = 0) to first excited (v = 1) vibrational state in collision with Au (111) at an incidence energy of translation of E (I) = 0. 45 eV.

CO

Au


Input: Unlike past work, we can exclude an excitation mechanism involving temporary adsorption on the surface followed by thermalization and desorption.


Input: The angular distributions of the scattered CO molecules are narrow, consistent with direct scattering occurring on a sub-ps time scale.

CO


Input: The absolute excitation probabilities are about 3% of those expected from thermal accommodation.


Input: The surface temperature dependence of excitation, which was measured between 373 and 973 K, is Arrhenius-like with an activation energy equal to the energy required for vibrational excitation.


Input: Our measurements are consistent with a vibrational excitation mechanism involving coupling of thermally excited electron-hole pairs of the solid to CO vibration.

CO


Input: Selective focused-ion-beam sculpting of TiO2 nanotubes and mechanism understanding.


Input: Anodic TiO (2) nanotubes with different structures, doping agents, and decorations have been studied in order to improve energy conversion and storage efficiencies such as in dye sensitized solar cells, solar fuels, and electrochemical supercapacitors.

TiO (2)


Input: However, the top surface modification of TiO (2) nanotubes has never been addressed.

TiO (2)


Input: In this study, anodic TiO (2) nanotubes have been selectively closed by high energy focused ion beams and re-opened by low energy focused ion beams.

TiO (2)


Input: Under a 30 kV Ga (+) beam, TiO (2) nanotubes are closed with a 65 nm shield layer covering the top entrance when the ion dose is larger than 1. 2 x 10 (17) ions per cm (2); under a 5 kV Ga (+) beam, the shield layer is removed and the closed tubes are re-opened.

Ga (+)

TiO (2)

Ga (+)


Input: An ion-induced viscous flow model has been proposed to explain the influence of Ga (+) ion beam flux, substrate temperature, initial tube diameter, ion beam dwell time, and the incidence angle of the ion beam.

Ga (+)


Input: Gene transcription reflects poor health status of resident European eel chronically exposed to environmental pollutants.


Input: Understanding the effects of chronic exposure to pollutants on the genome and transcriptome of diadromous fish populations is crucial for their resilience under combined anthropogenic and environmental selective pressures.


Input: The catadromous European eel (Anguilla anguilla L.) has suffered a dramatic decline in recruitment for three decades, necessitating a thorough assessment of the transcriptional effects of environmental pollutants on resident and migrating eels in natural systems.


Input: We investigated the relationship between muscular bioaccumulation levels of metals (Hg, Cd, Pb, Cu, Zn, Ni, Cr, As and Se), PCBs and organochlorine pesticides (DDTs), the health status (condition factor and lipid reserves) and the associated transcriptional response in liver and gill tissues for genes involved in metal detoxification (metallothionein, MT) and oxidative metabolism (cytochrome P4501A, CYP1A) of xenobiotic compounds.

Hg

Cd

Pb

Cu

Zn

Ni

Cr

As

Se

PCBs

DDTs


Input: In total 84 resident eels originating from three Belgian river basins (Scheldt, Meuse and Yzer) were analyzed along with five unpolluted aquaculture samples as control group.


Input: There was a large spatial variation in individual contaminant intensity and profile, while tissue pollution levels were strongly and negatively associated with condition indices, suggesting an important impact of pollution on the health of sub-adult resident eels.


Input: Gene transcription patterns revealed a complex response mechanism to a cocktail of pollutants, with a high variation at low pollution levels, but strongly down-regulated hepatic and gill gene transcription in highly polluted eels.


Input: Resident eels clearly experience a high pollution burden and seem to show a dysfunctional gene transcription regulation of detoxification genes at higher pollutant levels, correlated with low energy reserves and condition.


Input: To fully understand the evolutionary implications of pollutants on eel reproductive fitness, analyses of mature migrating eels and the characterization of their transcriptome-wide gene transcription response would be appropriate to unveil the complex responses associated with multiple interacting stressors and the long-term consequences at the entire species level.


Input: In the meanwhile, jointly monitoring environmental and tissue pollution levels at a European scale should be initiated, while preserving high quality habitats to increase the recovery chance of European eel in the future.


Input: A comparative VCD study of methyl mandelate in methanol, dimethyl sulfoxide, and chloroform: explicit and implicit solvation models.

methyl mandelate

methanol

dimethyl sulfoxide

chloroform


Input: Vibrational absorption (VA) and vibrational circular dichroism (VCD) spectra of methyl mandelate, a prototype chiral molecule, in a series of organic solvents, namely methanol (MeOH-d (4)), dimethyl sulfoxide (DMSO-d (6)), and chloroform (CDCl (3)), have been measured in the finger print region from 1800 to 1150 cm (-1).

methyl mandelate

methanol

MeOH-d (4)

dimethyl sulfoxide

DMSO-d (6)

chloroform

CDCl (3)


Input: Implicit solvation models in the form of polarizable continuum model and explicit solvation models have been employed independently and simultaneously.


Input: The goal is to evaluate their efficiencies in dealing with solvent effects in each solution and to establish a general strategy to adequately account for effects of solvents.


Input: Molecular dynamics (MD) simulation and radial distribution function analysis have been performed to aid the construction of the explicit solvation models.


Input: Initial geometry searches have been carried out at the B3LYP/6-31G (d) level for the methyl mandelate monomer and its explicit 1: 1 and 1: 2 solute-solvent hydrogen-bonded complexes.

methyl mandelate

hydrogen


Input: B3LYP/cc-pVTZ has been used for all the final geometry optimizations, the vibrational frequency, VA and VCD intensity, and optical rotation dispersion (ORD) calculations.


Input: The results show that inclusion of solvent explicitly and implicitly at the same time has significant impacts on the appearance of the VA and VCD spectra, and is crucial for reliable spectral assignments when solvents are capable of hydrogen-bonding interactions with solutes.

hydrogen


Input: When no strong solvent-solute hydrogen-bonding interactions in the case of chloroform are expected, the gas phase monomer model is adequate for spectral interpretation, while inclusion of implicit solvation improves the frequency agreement with experiment.

hydrogen

chloroform


Input: ORD spectra of methyl mandelate in the aforementioned solvents at different concentrations under 5 excitation wavelengths have also been measured.

methyl mandelate


Input: The comparison between the calculated and the experimental ORD spectra supports the conclusions drawn from the VA and VCD investigations.


Input: Association of Shiga toxin glycosphingolipid receptors with membrane microdomains of toxin-sensitive lymphoid and myeloid cells.

glycosphingolipid


Input: Glycosphingolipids (GSLs) of the globo-series constitute specific receptors for Shiga toxins (Stxs) released by certain types of pathogenic Escherichia coli strains.

Glycosphingolipids


Input: Stx-loaded leukocytes may act as transporter cells in the blood and transfer the toxin to endothelial target cells.


Input: Therefore, we performed a thorough investigation on the expression of globo-series GSLs in serum-free cultivated Raji and Jurkat cells, representing B-and T-lymphocyte descendants, respectively, as well as THP-1 and HL-60 cells of the monocyte and granulocyte lineage, respectively.


Input: The presence of Stx-receptors in GSL preparations of Raji and THP-1 cells and the absence in Jurkat and HL-60 cells revealed high compliance of solid-phase immunodetection assays with the expression profiles of receptor-related glycosyltransferases, performed by qRT-PCR analysis, and Stx2-caused cellular damage.


Input: Canonical microdomain association of Stx GSL receptors, sphingomyelin, and cholesterol in membranes of Raji and THP-1 cells was assessed by comparative analysis of detergent-resistant membrane (DRM) and nonDRM fractions obtained by density gradient centrifugation and showed high correlation based on nonparametric statistical analysis.

sphingomyelin

cholesterol


Input: Our comprehensive study on the expression of Stx-receptors and their subcellular distribution provides the basis for exploring the functional role of lipid raft-associated Stx-receptors in cells of leukocyte origin.


Input: Extremely flexible nanoscale ultrathin body silicon integrated circuits on plastic.

silicon


Input: In recent years, flexible devices based on nanoscale materials and structures have begun to emerge, exploiting semiconductor nanowires, graphene, and carbon nanotubes.

graphene

carbon


Input: This is primarily to circumvent the existing shortcomings of the conventional flexible electronics based on organic and amorphous semiconductors.


Input: The aim of this new class of flexible nanoelectronics is to attain high-performance devices with increased packing density.


Input: However, highly integrated flexible circuits with nanoscale transistors have not yet been demonstrated.


Input: Here, we show nanoscale flexible circuits on 60 A thick silicon, including functional ring oscillators and memory cells.

silicon


Input: The 100-stage ring oscillators exhibit the stage delay of ~ 16 ps at a power supply voltage of 0. 9 V, the best reported for any flexible circuits to date.


Input: The mechanical flexibility is achieved by employing the controlled spalling technology, enabling the large-area transfer of the ultrathin body silicon devices to a plastic substrate at room temperature.

silicon


Input: These results provide a simple and cost-effective pathway to enable ultralight flexible nanoelectronics with unprecedented level of system complexity based on mainstream silicon technology.

silicon


Input: Enhancement of the water solubility of flavone glycosides by disruption of molecular planarity of the aglycone moiety.

flavone glycosides


Input: Enhancement of the water solubility by disruption of molecular planarity has recently been reviewed as a feasible approach in small-molecule drug discovery programs.


Input: We applied this strategy to some natural flavone glycosides, especially diosmin, a highly insoluble citroflavonoid prescribed as an oral phlebotropic drug.

flavone glycosides

diosmin

citroflavonoid


Input: Disruption of planarity at the aglycone moiety by 3-bromination or chlorination afforded 3-bromo-and 3-chlorodiosmin, displaying a dramatic solubility increase compared with the parent compound.

3-bromo-and 3-chlorodiosmin


Input: Interplay between structure and relaxations in perfluorosulfonic acid proton conducting membranes.

perfluorosulfonic acid


Input: This study focuses on changes in the structure of ionomer membranes, provided by the 3M Fuel Cells Component Group, as a function of the equivalent weight (EW) and the relationship between the structure and the properties of the membrane.


Input: Wide-angle X-ray diffraction results showed evidence of both non-crystalline and crystalline ordered hydrophobic regions in all the EW membranes except the 700 EW membrane.


Input: The spectral changes evident in the vibrational spectra of the 3M membranes can be associated with two major phenomena: (1) dissociation of the proton from the sulfonic acid groups even in the presence of small amounts of water; and (2) changes in the conformation or the degree of crystallinity of the poly (tetrafluoroethylene) hydrophobic domains both as a function of EW and membrane water content.

sulfonic acid

poly (tetrafluoroethylene)


Input: All the membranes, regardless of EW, are thermally stable up to 360 degrees C.


Input: The wet membranes have conductivities between 7 and 20 mS/cm at 125 degrees C.


Input: In this condition, the conductivity values follow VTF behavior, which suggests that the proton migration occurs via proton exchange processes between delocalization bodies (DBs) that are facilitated by the dynamics of the host polymer.


Input: The conductivity along the interface between the hydrophobic and hydrophilic domains makes a larger contribution in the smaller EW membranes likely due to the existence of a greater number of interfaces in the membrane.


Input: The larger crystalline domains present in the higher EW membranes provide percolation pathways for charge migration between DBs, which reduces the probability of charge transfer along the interface.


Input: Therefore, at higher EWs although there is charge migration along the interface within the hydrophobic-hydrophilic domains, the exchange of protons between different DBs is likely the rate-limiting step of the overall conduction process.


Input: Phase behavior and molecular dynamics simulation studies of new aqueous two-phase separation systems induced by HEPES buffer.


Input: Here, for the first time, we show that with addition of a biological buffer, 4-(2-hydroxyethyl) piperazine-1-ethanesulfonic acid (HEPES), into aqueous solutions of tetrahydrofuran (THF), 1, 3-dioxolane, 1, 4-dioxane, 1-propanol, 2-propanol, tert-butanol, acetonitrile, or acetone, the organic solvent can be excluded from water to form a new liquid phase.

4-(2-hydroxyethyl) piperazine-1-ethanesulfonic acid

HEPES

tetrahydrofuran

THF

1, 3-dioxolane, 1, 4-dioxane, 1-propanol

tert-butanol

acetonitrile

acetone


Input: The phase diagrams have been determined at ambient temperature.


Input: In order to understand why and how a zwitterion solute (HEPES) induced phase separation of the investigated systems, molecular dynamics (MD) simulation studies are performed for HEPES + water + THF system.

HEPES

HEPES

THF


Input: The MD simulations were conducted for the aqueous mixtures with 12 different compositions.


Input: The reliability of the simulation results of HEPES in pure water and beyond the phase separation mixtures was justified by comparing the densities obtained from MD with the experimental values.

HEPES


Input: The simulation results of HEPES in pure THF and in a composition inside the phase separation region were justified qualitatively.

HEPES

THF


Input: Interestingly, all HEPES molecules entirely aggregated in pure THF.

HEPES

THF


Input: This reveals that HEPES is insoluble in pure THF, which is consistent with the experimental results.

HEPES

THF


Input: Even more interestingly, the MD simulation for the mixture with composition inside the phase separation region showed the formation of two phases.


Input: The THF molecules are squeezed out from the water network into a new liquid phase.

THF


Input: The hydrogen bonds (HBs), HB lifetime, HB Gibbs energy (Delta G), radial distribution functions (RDFs), coordination numbers (CNs), electrostatic interactions, and the van der Waals interactions between the different species have been analyzed.


Input: Further, MD simulations for the other phase separation systems by choosing a composition inside the two liquids region for each system were also simulated.


Input: Our findings will therefore pave the way for designing new benign separation auxiliary agents.


Input: Recent developments in the study of opioid receptors.


Input: It is now about 40 years since Avram Goldstein proposed the use of the stereoselectivity of opioid receptors to identify these receptors in neural membranes.


Input: In 2012, the crystal structures of the four members of the opioid receptor family were reported, providing a structural basis for understanding of critical features affecting the actions of opiate drugs.


Input: This minireview summarizes these recent developments in our understanding of opiate receptors.


Input: Receptor function is also influenced by amino acid substitutions in the protein sequence.

amino acid


Input: Among opioid receptor genes, one polymorphism is much more frequent in human populations than the many others that have been found, but the functional significance of this single nucleotide polymorphism (SNP) has been unclear.


Input: Recent studies have shed new light on how this SNP might influence opioid receptor function.


Input: In this minireview, the functional significance of the most prevalent genetic polymorphism among the opioid receptor genes is also considered.


Input: Mechanisms limiting distribution of the threonine-protein kinase B-RaF (V600E) inhibitor dabrafenib to the brain: implications for the treatment of melanoma brain metastases.

threonine

dabrafenib


Input: Brain metastases are a common cause of death in stage IV metastatic melanoma.


Input: Dabrafenib is a BRAF (gene encoding serine/threonine-protein kinase B-Raf) inhibitor that has been developed to selectively target the valine 600 to glutamic acid substitution (BRAF (V600E)), which is commonly found in metastatic melanoma.

serine

threonine

valine

glutamic acid


Input: Clinical trials with dabrafenib have shown encouraging results; however, the central nervous system distribution of dabrafenib remains unknown.

dabrafenib

dabrafenib


Input: Thus, the objective of the current study was to evaluate the brain distribution of dabrafenib in mice, and to see whether active efflux by P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) restricts its delivery across the blood-brain barrier (BBB).

dabrafenib


Input: In vitro accumulation studies conducted in Madin-Darby canine kidney II cells indicate that dabrafenib is an avid substrate for both P-gp and BCRP.

dabrafenib


Input: Directional flux studies revealed greater transport in the basolateral to apical direction with corrected efflux ratios greater than 2 for both P-gp and Bcrp1 transfected cell lines.


Input: In vivo, the ratio of area under the concentration-time curve (AUC) (brain) to AUC (plasma) (K (p)) of dabrafenib after an i. v. dose (2. 5 mg/kg) was 0. 023, which increased by 18-fold in Mdr1 a/b (-/-) Bcrp1 (-/-) mice to 0. 42.

dabrafenib


Input: Dabrafenib plasma exposure was ~ 2-fold greater in Mdr1 a/b (-/-) Bcrp1 (-/-) mice as compared with wild-type with an oral dose (25 mg/kg); however, the brain distribution was increased by ~ 10-fold with a resulting K (p) of 0. 25.

Dabrafenib


Input: Further, compared with vemurafenib, another BRAF (V600E) inhibitor, dabrafenib showed greater brain penetration with a similar dose.

vemurafenib

dabrafenib


Input: In conclusion, the dabrafenib brain distribution is limited in an intact BBB model, and the data presented herein may have clinical implications in the prevention and treatment of melanoma brain metastases.

dabrafenib


Input: Pharmacological inhibition of mitochondrial carbonic anhydrases protects mouse cerebral pericytes from high glucose-induced oxidative stress and apoptosis.

glucose


Input: Diabetes-associated complications in the microvasculature of the brain are caused by oxidative stress, generated by overproduction of reactive oxygen species from hyperglycemia-induced accelerated oxidative metabolism of glucose.

oxygen

glucose


Input: Pericytes, essential for the viability of the microvasculature, are especially susceptible to oxidative stress.


Input: Mitochondrial carbonic anhydrases, regulators of the oxidative metabolism of glucose, determine the rate of reactive oxygen species production and inhibition of mitochondrial carbonic anhydrases rescues glucose-induced pericyte loss in the diabetic mouse brain.

glucose

oxygen

glucose


Input: We hypothesized that high glucose induces intracellular oxidative stress and pericyte apoptosis and that inhibition of mitochondrial carbonic anhydrases protects pericytes from oxidative stress-induced apoptosis.

glucose


Input: To validate our hypothesis, conditionally immortalized cerebral pericyte (IPC) cultures were established from Immortomice to investigate the effect of high glucose on oxidative stress and pericyte apoptosis.

glucose


Input: The IPCs expressed pericyte markers and induced high transendothelial electrical resistance and low permeability in brain endothelial cell monolayers comparable with pericytes in primary cultures.


Input: The IPCs also secreted cytokines constitutively and in response to lipopolysaccharide similar to pericytes.


Input: High glucose caused oxidative stress and apoptosis of these cells, with both oxidative stress and apoptosis significantly reduced after mitochondrial carbonic anhydrase inhibition.

glucose


Input: These results provide the first evidence that pharmacological inhibition of mitochondrial carbonic anhydrases attenuates pericyte apoptosis caused by high glucose-induced oxidative stress.

glucose


Input: Carbonic anhydrase inhibitors have a long history of safe clinical use and can be immediately evaluated for this new indication in translational research.


Input: Thus, mitochondrial carbonic anhydrases may provide a new therapeutic target for oxidative stress-related illnesses of the brain.


Input: An engineered human follistatin variant: insights into the pharmacokinetic and pharmocodynamic relationships of a novel molecule with broad therapeutic potential.


Input: Human follistatin is a regulatory glycoprotein with widespread biologic functions, including antiinflammatory activities, wound-healing properties, and muscle-stimulating effects.


Input: The role of follistatin in a wide range of biologic activities shows promise for potential clinical application, which has prompted considerable interest in the investigation of the protein as a potential disease-modifying agent.


Input: In spite of this potential, the development of follistatin as a broad use biotherapeutic has been severely hindered by a poor understanding and characterization of its pharmacokinetic/pharmacodynamic (PK/PD) relationships.


Input: Therefore, to better define these relationships, we performed in-depth analyses of the PK/PD relationships of native follistatin-315 (FST315).


Input: Our data indicate that the intrinsic PK/PD properties of native FST315 are poorly suited for acting as a parentally administered biotherapeutic with broad systemic effects.


Input: Here, we leveraged protein engineering to modify the PK characteristics of the native molecule by fusing FST315 to a murine IgG (1) Fc and removing the intrinsic heparan sulfate-binding activity of follistatin.

sulfate


Input: The engineered variant molecule had ~ 100-and ~ 1600-fold improvements in terminal half-life and exposure, respectively.


Input: In contrast to the native FST315, the variant showed a robust, dose-dependent pharmacological effect when administered subcutaneously on a weekly basis in mouse models of muscle atrophy and degeneration.


Input: These studies highlight the underappreciated and critical relationship between optimizing multiple physical and chemical properties of follistatin on its overall PK/PD profile.


Input: Moreover, our findings provide the first documented strategy toward the development of a follistatin therapeutic with potential use in patients affected with skeletal muscle diseases.


Input: Rapid and specific purification of Argonaute-small RNA complexes from crude cell lysates.


Input: Small interfering RNAs (siRNAs) direct Argonaute proteins, the core components of the RNA-induced silencing complex (RISC), to cleave complementary target RNAs.


Input: Here, we describe a method to purify active RISC containing a single, unique small RNA guide sequence.


Input: We begin by capturing RISC using a complementary 2'-O-methyl oligonucleotide tethered to beads.


Input: Unlike other methods that capture RISC but do not allow its recovery, our strategy purifies active, soluble RISC in good yield.


Input: The method takes advantage of the finding that RISC partially paired to a target through its siRNA guide dissociates more than 300 times faster than a fully paired siRNA in RISC.


Input: We use this strategy to purify fly Ago1-and Ago2-RISC, as well as mouse AGO2-RISC.


Input: The method can discriminate among RISCs programmed with different guide strands, making it possible to deplete and recover specific RISC populations.


Input: Endogenous microRNA: Argonaute complexes can also be purified from cell lysates.


Input: Our method scales readily and takes less than a day to complete.


Input: Associations between diabetes, leanness, and the risk of death in the Japanese general population: the jichi medical school cohort study.


Input: OBJECTIVE To examine the BMI-stratified associations between diabetes and the risks of all-cause death, cardiovascular disease (CVD) death, and cancer death.


Input: RESEARCH DESIGN AND METHODS Using a prospective study with 12 rural Japanese general populations (n = 3, 641, mean age, 53. 7 years; 33. 5% men), we examined the associations between diabetes and the risk of all-cause death, CVD death, and cancer death.


Input: We also examined the effects of BMI and age on such associations.


Input: RESULTS During an average duration of 10. 2 years (37, 278 person-years), 240 deaths occurred (54 deaths from CVD, 101 from cancer, and 85 from other causes).


Input: Cox regression analysis showed leanness (defined as the lowest quartile of entire BMI; mean, 19. 5 kg/m (2)), but not obesity (BMI >= 25 kg/m (2)), and diabetes were independently associated with an increased risk of all-cause death (hazard ratio [HR] 1. 70 and 1. 65, respectively; both P < 0. 01.).


Input: Stratification with cause-specific deaths showed that leanness and obesity were associated with CVD death (HR 3. 77 and 2. 94, respectively), whereas diabetes was associated with cancer death (HR 1. 87; all P < 0. 05).


Input: The increased risk of all-cause death in diabetes was substantially higher in lean subjects aged < 65 years (HR 3. 4) or those aged >= 65 years (HR 4. 2), whereas the risk in obese diabetes patients was significant only in subjects aged < 65 years (HR 2. 32; all P < 0. 05).


Input: CONCLUSIONS Among the Japanese general population, diabetes confers an increased risk of all-cause death.


Input: Particular attention must be paid to the pronounced high mortality in diabetes accompanied with leanness, regardless of age.


Input: Evaluation of percutaneous absorption of esculetin: effect of chemical enhancers.

esculetin


Input: Percutaneous transdermal absorption of esculetin (6, 7-dihydroxycoumarin), an oxidative damage inhibitor, was evaluated by means of in vitro permeation studies in which vertical Franz-type diffusion cells and pig ear skin were employed.

esculetin

6, 7-dihydroxycoumarin


Input: To determine the absorption of esculetin, we validated a simple, accurate, precise, and rapid HPLC-UV method.

esculetin


Input: Additionally, the effects of several percutaneous enhancers were studied.


Input: Pretreatment of porcine skin was performed with ethanol (control vehicle), decenoic acid, oleic acid, R-(+)-limonene, and laurocapram (Azone (R)) (5% in ethanol, w/w, respectively).

ethanol

decenoic acid

oleic acid

R-(+)-limonene

laurocapram

Azone

ethanol


Input: Pretreatment of skin with oleic acid or laurocapram led to statistically significant differences in the transdermal flux of esculetin with respect to controls.

oleic acid

laurocapram

esculetin


Input: Of the two enhancers, laurocapram showed the greatest capacity to enhance the flux of esculetin across pig skin.

laurocapram

esculetin


Input: Design and exploration of novel boronic acid inhibitors reveals important interactions with a clavulanic acid-resistant sulfhydryl-variable (SHV) beta-lactamase.

boronic acid

clavulanic acid

sulfhydryl


Input: Inhibitor resistant (IR) class A beta-lactamases pose a significant threat to many current antibiotic combinations.


Input: The K234R substitution in the SHV beta-lactamase, from Klebsiella pneumoniae, results in resistance to ampicillin/clavulanate.

ampicillin

clavulanate


Input: After site-saturation mutagenesis of Lys-234 in SHV, microbiological and biochemical characterization of the resulting beta-lactamases revealed that only-Arg conferred resistance to ampicillin/clavulanate.

Lys

Arg

ampicillin

clavulanate


Input: X-ray crystallography revealed two conformations of Arg-234 and Ser-130 in SHV K234R.

Arg

Ser


Input: The movement of Ser-130 is the principal cause of the observed clavulanate resistance.

Ser

clavulanate


Input: A panel of boronic acid inhibitors was designed and tested against SHV-1 and SHV K234R.

boronic acid


Input: A chiral ampicillin analogue was discovered to have a 2. 4 +/- 0. 2 nM K (i) for SHV K234R; the chiral ampicillin analogue formed a more complex hydrogen-bonding network in SHV K234R vs SHV-1.

ampicillin

ampicillin

hydrogen


Input: Consideration of the spatial position of Ser-130 and Lys-234 and this hydrogen-bonding network will be important in the design of novel antibiotics targeting IR beta-lactamases.

Ser

Lys

hydrogen


Input: Architecturing hierarchical function layers on self-assembled viral templates as 3D nano-array electrodes for integrated Li-ion microbatteries.

Li


Input: This work enables an elegant bottom-up solution to engineer 3D microbattery arrays as integral power sources for microelectronics.


Input: Thus, multilayers of functional materials were hierarchically architectured over tobacco mosaic virus (TMV) templates that were genetically modified to self-assemble in a vertical manner on current-collectors, so that optimum power and energy densities accompanied with excellent cycle-life could be achieved on a minimum footprint.


Input: The resultant microbattery based on self-aligned LiFePO (4) nanoforests of shell-core-shell structure, with precise arrangement of various auxiliary material layers including a central nanometric metal core as direct electronic pathway to current collector, delivers excellent energy density and stable cycling stability only rivaled by the best Li-ion batteries of conventional configurations, while providing rate performance per foot-print and on-site manufacturability unavailable from the latter.

LiFePO (4)

Li


Input: This approach could open a new avenue for microelectromechanical systems (MEMS) applications, which would significantly benefit from the concept that electrochemically active components be directly engineered and fabricated as an integral part of the integrated circuit (IC).


Input: Selective separation of similarly sized proteins with tunable nanoporous block copolymer membranes.


Input: An integral asymmetric membrane was fabricated in a fast and one-step process by combining the self-assembly of an amphiphilic block copolymer (PS-b-P4VP) with nonsolvent-induced phase separation.


Input: The structure was found to be composed of a thin layer of densely packed highly ordered cylindrical channels with uniform pore sizes perpendicular to the surface on top of a nonordered sponge-like layer.


Input: The as-assembled membrane obtained a water flux of more than 3200 L m (-2) h (-1) bar (-1), which was at least an order of magnitude higher than the water fluxes of commercially available membranes with comparable pore sizes, making this membrane particularly well suited to size-selective and charge-based separation of biomolecules.


Input: To test the performance of the membrane, we conducted diffusion experiments at the physiological pH of 7. 4 using bovine serum albumin (BSA) and globulin-gamma, two proteins with different diameters but too close in size (2-fold difference in molecular mass) to be efficiently separated via conventional dialysis membrane processes.


Input: The diffusion rate differed by a factor of 87, the highest value reported to date.


Input: We also analyzed charge-based diffusive transport and separation of two proteins of similar molecular weight (BSA and bovine hemoglobin (BHb)) through the membrane as a function of external pH.


Input: The membrane achieved a selectivity of about 10 at pH 4. 7, the isoelectric point (pI) of BSA.


Input: We then positively charged the membrane to improve the separation selectivity.


Input: With the modified membrane BSA was completely blocked when the pH was 7. 0, the pI of BHb, while BHb was completely blocked at pH 4. 7.


Input: Our results demonstrate the potential of our asymmetric membrane to efficiently separate biological substances/pharmaceuticals in bioscience, biotechnology, and biomedicine applications.


Input: Low-noise nano superconducting quantum interference device operating in Tesla magnetic fields.


Input: Superconductivity in the cuprate YBa (2) Cu (3) O (7) (YBCO) persists up to huge magnetic fields (B) up to several tens of Teslas, and sensitive direct current (dc) superconducting quantum interference devices (SQUIDs) can be realized in epitaxially grown YBCO films by using grain boundary Josephson junctions (GBJs).

YBa (2) Cu (3) O (7)

YBCO

YBCO


Input: Here we present the realization of high-quality YBCO nanoSQUIDs, patterned by focused ion beam milling.

YBCO


Input: We demonstrate low-noise performance of such a SQUID up to B = 1 T applied parallel to the plane of the SQUID loop at the temperature T = 4. 2 K.


Input: The GBJs are shunted by a thin Au layer to provide nonhysteretic current voltage characteristics, and the SQUID incorporates a 90 nm wide constriction which is used for on-chip modulation of the magnetic flux through the SQUID loop.

Au


Input: The white flux noise of the device increases only slightly from 1. 3 mu Phi (0)/(Hz) (1/2) at B = 0 to 2. 3 mu Phi (0)/(Hz)) (1/2) at 1 T.


Input: Assuming that a point-like magnetic particle with magnetization in the plane of the SQUID loop is placed directly on top of the constriction and taking into account the geometry of the SQUID, we calculate a spin sensitivity S (mu) (1/2) = 62 mu (B)/(Hz)) (1/2) at B = 0 and 110 mu (B)/(Hz)) (1/2) at 1 T.


Input: The demonstration of low noise of such a SQUID in Tesla fields is a decisive step toward utilizing the full potential of ultrasensitive nanoSQUIDs for direct measurements of magnetic hysteresis curves of magnetic nanoparticles and molecular magnets.


Input: Role of pharmacogenetics in busulfan/cyclophosphamide conditioning therapy prior to hematopoietic stem cell transplantation.

busulfan

cyclophosphamide


Input: Hematopoietic stem cell transplantation (HSCT) is a curative treatment for several malignant and nonmalignant disorders.


Input: Busulfan (Bu) and cyclophosphamide (Cy) are the most commonly used alkylators in high-dose pretransplant conditioning for HSCT; a treatment that is correlated with drug-related toxicity and relapse.

Busulfan

cyclophosphamide


Input: Pharmacogenetic investigations have shown that CYP450, as well as aldehyde dehydrogenase, are clearly involved with Cy metabolism and are associated with altered treatment response, Cy metabolism and the unique stem-cell sparing capacity.

aldehyde


Input: Moreover, glutathione-S-transferase isoenzymes have been associated with cellular outward transport of various alkylating agents, including Cy metabolites, melphalan, Bu and chlorambucil.

glutathione

S

melphalan

chlorambucil


Input: A shift from genetic-based studies to whole-genome-based investigations of Cy-and Bu-associated markers may contribute to personalizing the conditioning therapy and enhancing the clinical outcome of HSCT.


Input: Mass accommodation of water: bridging the gap between molecular dynamics simulations and kinetic condensation models.


Input: The condensational growth of submicrometer aerosol particles to climate relevant sizes is sensitive to their ability to accommodate vapor molecules, which is described by the mass accommodation coefficient.


Input: However, the underlying processes are not yet fully understood.


Input: We have simulated the mass accommodation and evaporation processes of water using molecular dynamics, and the results are compared to the condensation equations derived from the kinetic gas theory to shed light on the compatibility of the two.


Input: Molecular dynamics simulations were performed for a planar TIP4P-Ew water surface at four temperatures in the range 268-300 K as well as two droplets, with radii of 1. 92 and 4. 14 nm at T = 273. 15 K.


Input: The evaporation flux from molecular dynamics was found to be in good qualitative agreement with that predicted by the simple kinetic condensation equations.


Input: Water droplet growth was also modeled with the kinetic multilayer model KM-GAP of Shiraiwa et al.


Input: [Atmos. Chem. Phys. 2012, 12, 2777].


Input: It was found that, due to the fast transport across the interface, the growth of a pure water droplet is controlled by gas phase diffusion.


Input: These facts indicate that the simple kinetic treatment is sufficient in describing pure water condensation and evaporation.


Input: The droplet size was found to have minimal effect on the value of the mass accommodation coefficient.


Input: The mass accommodation coefficient was found to be unity (within 0. 004) for all studied surfaces, which is in agreement with previous simulation work.


Input: Additionally, the simulated evaporation fluxes imply that the evaporation coefficient is also unity.


Input: Comparing the evaporation rates of the mass accommodation and evaporation simulations indicated that the high collision flux, corresponding to high supersaturation, present in typical molecular dynamics mass accommodation simulations can under certain conditions lead to an increase in the evaporation rate.


Input: Consequently, in such situations the mass accommodation coefficient can be overestimated, but in the present cases the corrected values were still close to unity with the lowest value at =~ 0. 99.


Input: Accounting for receptor flexibility and enhanced sampling methods in computer-aided drug design.


Input: Protein flexibility plays a major role in biomolecular recognition.


Input: In many cases, it is not obvious how molecular structure will change upon association with other molecules.


Input: In proteins, these changes can be major, with large deviations in overall backbone structure, or they can be more subtle as in a side-chain rotation.


Input: Either way the algorithms that predict the favorability of biomolecular association require relatively accurate predictions of the bound structure to give an accurate assessment of the energy involved in association.


Input: Here, we review a number of techniques that have been proposed to accommodate receptor flexibility in the simulation of small molecules binding to protein receptors.


Input: We investigate modifications to standard rigid receptor docking algorithms and also explore enhanced sampling techniques, and the combination of free energy calculations and enhanced sampling techniques.


Input: The understanding and allowance for receptor flexibility are helping to make computer simulations of ligand protein binding more accurate.


Input: These developments may help improve the efficiency of drug discovery and development.


Input: Efficiency will be essential as we begin to see personalized medicine tailored to individual patients, which means specific drugs are needed for each patient' s genetic makeup.


Input: Vasorelaxing effects and inhibition of nitric oxide in macrophages by new iron-containing carbon monoxide-releasing molecules (CO-RMs).

nitric oxide

iron

carbon monoxide


Input: Carbon monoxide-releasing molecules (CO-RMs) are a class of organometallo carbonyl complexes capable of delivering controlled quantities of CO gas to cells and tissues thus exerting a broad spectrum of pharmacological effects.

Carbon monoxide

CO

organometallo carbonyl

CO


Input: Here we report on the chemical synthesis, CO releasing properties, cytotoxicity profile and pharmacological activities of four novel structurally related iron-allyl carbonyls.

CO

iron-allyl carbonyls


Input: The major difference among the new CO-RMs tested was that three compounds (CORM-307, CORM-308 and CORM-314) were soluble in dimethylsulfoxide (DMSO), whereas a fourth one (CORM-319) was rendered water-soluble by reacting the iron-carbonyl with hydrogen tetrafluoroborate.

CO

dimethylsulfoxide

DMSO

iron-carbonyl

hydrogen tetrafluoroborate


Input: We found that despite the fact all compounds liberated CO, CO-RMs soluble in DMSO caused a more pronounced toxic effect both in vascular and inflammatory cells as well as in isolated vessels.

CO

CO

DMSO


Input: More specifically, iron carbonyls soluble in DMSO released CO with a fast kinetic and displayed a marked cytotoxic effect in smooth muscle cells and RAW 247. 6 macrophages despite exerting a rapid and pronounced vasorelaxation ex vivo.

iron carbonyls

DMSO

CO


Input: In contrast, CORM-319 that is soluble in water and liberated CO with a slower rate, preserved smooth muscle cell viability, relaxed aortic tissue and exerted a significant anti-inflammatory effect in macrophages challenged with endotoxin.

CO


Input: These data suggest that iron carbonyls can be used as scaffolds for the design and synthesis of pharmacologically active CO-RMs and indicate that increasing water solubility and controlling the rate of CO release are important parameters for limiting their potential toxic effects.

iron carbonyls

CO

CO


Input: Estradiol negative and positive feedback in a prenatal androgen-induced mouse model of polycystic ovarian syndrome.

Estradiol

androgen


Input: Gonadal steroid hormone feedback is impaired in polycystic ovarian syndrome (PCOS), a common endocrine disorder characterized by hyperandrogenism and an associated increase in LH pulse frequency.

steroid


Input: Using a prenatal androgen (PNA)-treated mouse model of PCOS, we aimed to investigate negative and positive feedback effects of estrogens on the hypothalamic-pituitary axis regulation of LH.

androgen

estrogens


Input: PNA-treated mice exhibited severely disrupted estrous cycles, hyperandrogenism, significantly reduced fertility, and altered ovarian morphology.


Input: To assess the negative feedback effects of estrogens, LH was measured before and after ovariectomy and after estradiol (E2) administration.

estrogens

estradiol


Input: Compared with controls, PNA-treated mice exhibited a blunted postcastration rise in LH (P <. 001) and an absence of LH suppression after E2 administration.


Input: To assess E2-positive feedback, control and PNA-treated GnRH-green fluorescent protein transgenic mice were subjected to a standard ovariectomy with E2-replacement regimen, and both plasma and perfusion-fixed brains were collected at the time of the expected GnRH/LH surge.


Input: Immunocytochemistry and confocal imaging of cFos and green fluorescent protein were used to assess GnRH neuron activation and spine density.


Input: In the surged group, both control and PNA-treated mice had significantly increased LH and cFos activation in GnRH neurons (P <. 05) compared with nonsurged animals.


Input: Spine density was quantified in cFos-positive and-negative GnRH neurons to examine whether there was an increase in spine density in cFos-expressing GnRH neurons of surged mice as expected.


Input: A significant increase in spine density in cFos-expressing GnRH neurons was evident in control animals; however, no significant increase was observed in the PNA-treated mice because spine density was elevated across all GnRH neurons.


Input: These data support that PNA treatment results in a PCOS-like phenotype that includes impaired E2-negative feedback.


Input: Additionally, although E2-positive feedback capability is retained in PNA mice, elevated GnRH neuron spine density may reflect altered synaptic regulation.


Input: Inhibitory effects of a bazedoxifene/conjugated equine estrogen combination on human breast cancer cells in vitro.

bazedoxifene

estrogen


Input: Breast cancer incidence is increased in women receiving menopausal hormone therapy with estrogen plus progestin but not with estrogen alone.

estrogen

estrogen


Input: The use of a tissue-selective estrogen complex (TSEC) has been proposed as a novel menopausal hormone therapy strategy to eliminate the requirement for a progestogen.

estrogen

progestogen


Input: Combination of bazedoxifene (BZA) with conjugated estrogens (CEs), the first TSEC, has shown beneficial effects.

bazedoxifene

BZA

estrogens


Input: Whether it would exert antiestrogenic effects on breast cancer is not clear.


Input: To address this issue, we compared estradiol (E (2)) and CE alone on proliferation and apoptosis in MCF-7 breast cancer cells.

estradiol


Input: CE stimulated growth of MCF-7 cells at a peak concentration 10-fold higher than required for E (2).


Input: Both CE and E (2) alone increased DNA synthesis and reduced apoptosis with activation of MAPK, Akt, and p70S6K and up-regulation of antiapoptotic factors survivin, Bcl-2, and X-linked inhibitor of apoptosis protein, These effects could be completely blocked by BZA.

BZA


Input: Gene expression studies demonstrated that CE and E (2) were equally potent on expression of cMyc, pS2, and WNT1 inducible signaling pathway protein 2, whereas the stimulatory effects of CE on progesterone receptor and amphiregulin expression were weaker than E (2).

progesterone


Input: BZA effectively blocked each of these effects and showed no estrogen agonistic effects when used alone.

BZA

estrogen


Input: Our results indicate that the stimulatory effects of E (2) or CE on breast cancer cells could be completely abrogated by BZA.

BZA


Input: These studies imply that the CE/BZA, TSEC, exerts antiestrogenic effects on breast cancer cells and might block the growth of occult breast neoplasms in postmenopausal women, resulting in an overall reduction in tumor incidence.

BZA


Input: Synthesis and characterization of self-bridged silver vanadium oxide/CNTs composite and its enhanced lithium storage performance.

silver vanadium oxide

lithium


Input: The improvement of the electrochemical properties of electrode materials with large capacity and good capacity retention is becoming an important task in the field of lithium ion batteries (LIBs).

lithium


Input: We designed a function-oriented hybrid material consisting of silver vanadium oxide (beta-AgVO (3)) nanowires modified with uniform Ag nanoparticles and multi-walled carbon nanotubes (CNTs) as a high-performance cathode material for LIBs.

silver vanadium oxide

AgVO (3)

Ag

carbon


Input: The Ag nanoparticles which precipitated automatically in the synthetic process act as a bridge between the beta-AgVO (3) nanowires and CNTs, creating a self-bridged network structure.

Ag

AgVO (3)


Input: The Ag particles at the junction of the nanowires and CNTs facilitate electron transport from the CNTs to the nanowires, and thereby improve the electrical conductivity of the beta-AgVO (3) nanowires and the composite.

Ag

AgVO (3)


Input: Moreover, the self-bridged network is hierarchically porous with a high surface area.


Input: When used as a cathode material, this composite electrode reveals high discharge capacities, excellent rate capability, and good cycling stability.


Input: The improved performance of the composite arises from its unique nanosized beta-AgVO (3) nanowires with short diffusion pathway for lithium ions, efficient electron collection and transfer in the presence of Ag nanoparticles, together with excellent electrical conductivity of CNTs.

AgVO (3)

lithium

Ag


Input: Noncanonical WNT-5A signaling regulates TGF-beta-induced extracellular matrix production by airway smooth muscle cells.


Input: Transforming growth factor beta (TGF-beta), a key mediator of fibrotic responses, is increased in asthma and drives airway remodeling by inducing expression of extracellular matrix (ECM) proteins.


Input: We investigated the molecular mechanisms underlying TGF-beta-induced ECM expression by airway smooth muscle cells and demonstrate a novel link between TGF-beta and Wingless/integrase 1 (WNT) signaling in ECM deposition.


Input: Airway smooth muscle expresses abundant WNT ligands, with the noncanonical WNT-5A being the most profoundly expressed.


Input: Interestingly, WNT-5A shows ~ 2-fold higher abundance in airway smooth muscle cells isolated from individuals with asthma than individuals without asthma.


Input: WNT-5A is markedly induced in response to TGF-beta (4-16-fold; EC50 0. 3 ng/ml) and is required for collagen and fibronectin expression by airway smooth muscle.


Input: WNT-5A engages noncanonical WNT signaling pathways, as inhibition of Ca (2 +) and c-Jun N-terminal kinase (JNK) signaling attenuated this TGF-beta response, whereas the canonical WNT antagonist Dickkopf 1 (DKK-1) did not.

Ca (2 +)

N


Input: Accordingly, WNT-5A induced JNK phosphorylation and nuclear translocation of nuclear factor of activated T cells c1 (NFATc1).


Input: Furthermore, silencing of the WNT-5A receptors Frizzled 8 (FZD8) and RYK attenuated TGF-beta-induced ECM expression.


Input: Collectively, these findings demonstrate that noncanonical WNT-5A signaling is activated by and necessary for TGF-beta-induced ECM production by airway smooth muscle cells, which could have significance in asthma pathogenesis.-Kumawat, K., Menzen, M.


Input: H.., Bos, I.


Input: S.


Input: T., Baarsma, H.


Input: A., Borger, P., Roth, M., Tamm, M., Halayko, A.


Input: J., Simoons, M., Prins, A., Postma, D.


Input: S., Schmidt, M., and Gosens, R.


Input: Noncanonical WNT-5A signaling regulates TGF-beta-induced extracellular matrix production by airway smooth muscle cells.


Input: The photophysics of 7-(N, N'-diethylamino) coumarin-3-carboxylic acid in water/AOT/isooctane reverse micelles: an excitation wavelength dependent study.

7-(N, N'-diethylamino) coumarin-3-carboxylic acid

AOT

isooctane


Input: In this manuscript we have studied the photophysics of 7-(N, N'-diethylamino) coumarin-3-carboxylic acid (7-DCCA) in water/AOT/isooctane reverse micelles.

7-(N, N'-diethylamino) coumarin-3-carboxylic acid

AOT

isooctane


Input: For this purpose we have used steady state absorption and fluorescence emission spectroscopy and time resolved fluorescence spectroscopy.


Input: We have studied the spectral behaviour of 7-DCCA inside the water/AOT/isooctane reverse micelles with variation of excitation wavelength.

AOT

isooctane


Input: We have studied the dynamics of solvent and rotational relaxation by using two different excitation wavelengths (lambda (exi) = 375 nm and lambda (exi) = 405 nm).


Input: We have observed the excitation wavelength dependent dynamics of 7-DCCA in the reverse micelles.


Input: The fluorescence quantum yield, decay time, solvent relaxation time and rotational relaxation time of 7-DCCA in reverse micelles vary with the excitation wavelength.


Input: A two step and wobbling-in-cone model was used to interpret the rotational relaxation dynamics of 7-DCCA in reverse micelles.


Input: Capture and stimulated release of circulating tumor cells on polymer-grafted silicon nanostructures.

silicon


Input: A platform for capture and release of circulating tumor cells is demonstrated by utilizing polymer grafted silicon nanowires.

silicon


Input: In this platform, integration of ligand-receptor recognition, nanostructure amplification, and thermal responsive polymers enables a highly efficient and selective capture of cancer cells.


Input: Subsequently, these captured cells are released upon a physical stimulation with outstanding cell viability.


Input: Characterization of disease-associated N-linked glycoproteins.

N


Input: N-linked glycoproteins play important roles in biological processes, including cell-to-cell recognition, growth, differentiation, and programmed cell death.

N


Input: Specific N-linked glycoprotein changes are associated with disease progression and identification of these N-linked glycoproteins has potential for use in disease diagnosis, prognosis, and prediction of treatments.

N

N


Input: In this review, we summarize common strategies for N-linked glycoprotein characterization and applications of these strategies to identification of glycoprotein changes associated with disease states.

N


Input: We also review the N-linked glycoproteins altered in diseases such as breast cancer, lung cancer, and prostate cancer.

N


Input: Although assays for these glycoproteins have potential clinical utility, research is needed to translate these glycoproteins to clinical biomarkers.


Input: Effect of guanidinylation on the properties of poly (2-aminoethylmethacrylate)-based antibacterial materials.

poly (2-aminoethylmethacrylate)


Input: The effect of converting ammonium into guanidine moieties, compared to other factors such as molecular weight or hydrophobicity, on the antibacterial activity is investigated for homo-and copolymers of 2-aminoethylmethacrylate in solution or coatings.

ammonium

guanidine


Input: Polymers are obtained by free radical polymerization, polymer-analogous guanidinylation is conducted with cyanamide; non-leaching immobilization is achieved by LBL assembly of homopolymers or crosslinking of functional sidegroups in copolymers.

cyanamide


Input: Antibacterial activity to Escherichia coli or Bacillus subtilis is determined by different standard methods.


Input: Guanidinylation improves antibacterial activity and speed as well as cytotoxicity of hydrophilic homo-and copolymers in solution or coatings.


Input: A metabonomics investigation of multiple sclerosis by nuclear magnetic resonance.


Input: Multiple sclerosis (MS) is a nervous system disease that affects the fatty myelin sheaths around the axons of the brain and spinal cord, leading to demyelination and a broad range of signs and symptoms.


Input: MS can be difficult to diagnose because its signs and symptoms may be similar to other medical problems.


Input: To find out which metabolites in serum are effective for the diagnosis of MS, we utilized metabolic profiling using proton nuclear magnetic resonance spectroscopy ((1) H-NMR).

(1) H


Input: Random forest (RF) was used to classify the MS patients and healthy subjects.


Input: Atomic absorption spectroscopy was used to measure the serum levels of selenium.

selenium


Input: The results showed that the levels of selenium were lower in the MS group, when compared with the control group.

selenium


Input: RF was used to identify the metabolites that caused selenium changes in people with MS by building a correlation model between these metabolites and serum levels of selenium.

selenium

selenium


Input: For the external test set, the obtained classification model showed a 93% correct classification of MS and healthy subjects.


Input: The regression model of levels of selenium and metabolites showed the correlation (R (2)) value of 0. 88 for the external test set.

selenium


Input: The results indicate the suitability of NMR as a screen for identifying MS patients and healthy subjects.


Input: A novel model with good prediction outcomes was constructed between serum levels of selenium and NMR data.

selenium


Input: Nanoscale thermomechanics of wear-resilient polymeric bilayer systems.


Input: We explore the effect of an ultrathin elastic coating to optimize the mechanical stability of an underlying polymer film for nanoscale applications.


Input: The coating consists of a several nanometer thin plasma-polymerized norbornene layer.

norbornene


Input: Scanning probes are used to characterize the system in terms of shear-force-induced wear and thermally assisted indentation.


Input: The layer transforms a weakly performing polystyrene film into a highly wear-resistive system, ideal for high-density and low-power data storage applications.

polystyrene


Input: The result can be understood from the indentation characteristics with a hot and sharp indenter tip.


Input: The latter gives rise to a deformation mode in the fully plastic regime, enabling a simple interpretation of the results.


Input: The softening transition and the yield stress of the system on a microsecond time scale and a nanometer size scale were obtained.


Input: We show that the plastic deformation is governed by yielding in the polystyrene sublayer, which renders the overall system soft for plastic deformation.

polystyrene


Input: The ultrathin protection layer contributes as an elastic skin, which shields part of the temperature and pressure and enables the high wear resistance against lateral forces.


Input: Moreover, the method of probing polymers at microsecond and nanometer size scales opens up new opportunities for studying polymer physics in a largely unexplored regime.


Input: Thus, we find softening temperatures of more than 100 degrees C above the polystyrene glass transition, which implies that for the short interaction time scales the glassy state of the polymer is preserved up to this temperature.

polystyrene


Input: Aspartic protease inhibitors: effective drugs against the human fungal pathogen Candida albicans.


Input: Candida albicans can invade humans and may lead to mucosal and skin infections or to deep-seated mycoses of almost all inner organs, especially in immunocompromised patients.


Input: In this context, both the host immune status and the ability of C. albicans to modulate the expression of its virulence factors are relevant aspects that drive the candidal susceptibility or resistance; in this last case, culminating in the establishment of successful infection known as candidiasis.


Input: C. albicans possesses a potent armamentarium consisting of several virulence molecules that help the fungal cells to escape from the host immune responses.


Input: There is no doubt that the secretion of aspartic proteases, designated as Saps, is one of the major virulence attributes produced by C. albicans cells, since these hydrolytic enzymes participate in a wide range of fungal physiological processes as well as in different facets of the fungal-host interactions.


Input: For these reasons, Saps clearly hold promise as new potential drug targets.


Input: Corroborating this hypothesis, the introduction of anti-human immunodeficiency virus drugs of the aspartic protease inhibitor-type (HIV PIs) have emerged as new agents for the inhibition of Saps.


Input: The introduction of HIV PIs has revolutionized the treatment of HIV disease, reducing the opportunistic infections, especially candidiasis.


Input: The attenuation of candidal infections in HIV-infected individuals might not solely has not only resulted from improved immunological status, but also as a result of direct inhibition of C. albicans Saps as well as the blockage of several biological processes controlled by these proteolytic enzymes.


Input: The present article will discuss the updates on the functional implications of HIV PIs on the development of candidiasis.


Input: Optical activity of achiral ligand SCH3 adsorbed on achiral Ag55 clusters: relationship between adsorption site and circular dichroism.


Input: The electronic circular dichroism (CD) spectra of a methyl-thiol adsorbed at different sites on an icosahedral silver nanoparticle is studied by using time-perturbed density functional theory.

methyl-thiol

silver


Input: Despite that separately molecule and nanoparticle are achiral and consequently optically inactive, the Ag (55)-SCH (3) compound emerges with a new symmetry, which may be chiral or not depending on the adsorption site and orientation of the molecule.

Ag (55)-SCH (3)


Input: It is found that chirality is favored when the thiol is adsorbed between two atoms of different coordination number.

thiol


Input: Chiral compounds have characteristic CD spectra in the UV-visible region, where Ag (55) shows optical absorption but SCH (3) does not; revealing that highly degenerated molecular-like electronic states of Ag (55) are modified by the presence of the molecule inducing optical activity.

Ag (55)

SCH (3)

Ag (55)


Input: It is concluded that CD line-shapes and magnitude strongly depend on the site where the adsorption takes place, while its intensity is modulated by the molecule orientation.


Input: Surfactant-Assisted Assembly of Fullerene (C (60)) Nanorods and Nanotubes Formed at a Liquid-Liquid Interface.

Fullerene

C (60)


Input: Herein we report the surfactant-triggered assembly of fullerene (C (60)) into 3D flowerlike microcrystals at the liquid-liquid interface.

fullerene

C (60)


Input: C (60) crystals were grown using a liquid-liquid interfacial precipitation (LLIP) method by layering surfactant solution in butanol with a saturated solution of C (60) in benzene.

C (60)

butanol

C (60)

benzene


Input: In the LLIP method, it is suggested that the crystal formation mechanism is driven by supersaturation related to the low C (60) solubility in alcohol.

C (60)


Input: We found that the dimensions of the synthesized C (60) flowers depend on the concentration and surfactant type.

C (60)


Input: In the absence of surfactant (i. e., in the butanol/benzene system), 1D C (60) nanowhiskers (nanorods) and C (60) nanotubes (diameter 400 nm-2 mu m and length 5-20 mu m) are obtained.

butanol

benzene

C (60)

C (60)


Input: However, when surfactants are incorporated into the system flowerlike microcrystals consisting of C (60) nanotubes are observed.

C (60)


Input: For instance, crystals grown at the interface of a 0. 01% diglycerol monolaurate (C (12) G (2)) nonionic surfactant in butanol with benzene lead to the formation of flower-shaped microcrystals of average sizes in the range of 10-35 mu m.

diglycerol monolaurate

C (12) G (2)

butanol

benzene


Input: To the best of our knowledge, this is the first example of the surfactant-assisted assembly of C (60) crystals.

C (60)


Input: X-ray diffraction (XRD) and transmission electron microscopy (TEM) measurements have shown that fullerene flowers have a hexagonal structure with cell dimensions of a = 2. 539 nm and c = 1. 021 nm, which differ from that of pristine C (60).

fullerene

C (60)


Input: Mixtures of flower-shaped C (60) crystals and free-standing C (60) nanotubes are found in the 0. 1% C (12) G (2)/butanol system.

C (60)

C (60)

C (12) G (2)

butanol


Input: However, clusters or giant aggregates of nanowhiskers lacking any specific shape are observed in the 1% C (12) G (2)/butanol system although these crystals exhibit hexagonal close-packed structures.

C (12) G (2)


Input: Flower-shaped C (60) microcrystals are also observed with anionic surfactants cetyltrimethylammonium bromide (CTAB) and cetyltrimethylammonium chloride (CTAC).

C (60)

cetyltrimethylammonium bromide

CTAB

cetyltrimethylammonium chloride

CTAC


Input: C (60) flowers obtained from 0. 01% CTAB and 0. 01% CTAC also exhibit hexagonal structures with cell dimensions of a = 2. 329 nm and c = 1. 273 nm, a = 2. 459 nm and c = 0. 938 nm, respectively.

C (60)

CTAB

CTAC


Input: Our C (60) flowers exhibit intense photoluminescence (PL) and a blue-shifted PL intensity maximum compared to the same parameters for pristine C (60), demonstrating the potential to control the optoelectronic properties of fullerene-based nanostructures.

C (60)

C (60)

fullerene


Input: Evaluation of drug interactions of GSK1292263 (a GPR119 agonist) with statins: from in vitro data to clinical study design.


Input: 1. This work investigated the drug interaction potential of GSK1292263, a novel GPR119 agonist, with the HMG-coA reductase inhibitors simvastatin and rosuvastatin.

simvastatin

rosuvastatin


Input: 2. In vitro experiments assessed the inhibition of transporters and CYP enzymes by GSK1292263, and a clinical drug interaction study investigated the effect of GSK1292263 (300 mg BID) on the pharmacokinetic profile of simvastatin (40 mg single dose) and rosuvastatin (10 mg single dose).

simvastatin

rosuvastatin


Input: 3. In vitro, GSK1292263 demonstrated little/weak inhibition (IC50 values > 30 mu M) towards CYPs (CYP1A2, 2C9, 2C19, 2D6, 3A4), Pgp, OATP1B3, or OCT2.


Input: However, GSK1292263 inhibited BCRP and OATP1B1, which are transporters involved in statin disposition.


Input: 4. In the clinical study, small increases in the AUC (0-inf) of simvastatin [mean ratio (90% CI) of 1. 34 (1. 22, 1. 48)] and rosuvastatin [mean ratio (90% CI) of 1. 39 (1. 30, 1. 49)] were observed when co-administered with GSK1292263, which is consistent with an inhibitory effect on intestinal BCRP and CYP3A4.

simvastatin

rosuvastatin


Input: In contrast, GSK1292263 did not inhibit OATP1B1 based on the lack of changes in simvastatin acid exposure [mean AUC (0-inf) ratio (90% CI) of 1. 05 (0. 91, 1. 21)].

simvastatin


Input: 5. GSK1292263 has a weak drug interaction with simvastatin and rosuvastain.

simvastatin

rosuvastain


Input: This study provides a mechanistic understanding of the in vivo inhibition of transporters and enzymes by GSK1292263.


Input: Iridium-catalyzed enantioselective allylic vinylation.

Iridium


Input: The first example of Ir-catalyzed asymmetric substitution reaction with vinyl trifluoroborates is described.

Ir

vinyl trifluoroborates


Input: The direct reaction between branched, racemic allylic alcohols and potassium alkenyltrifluoroborates proceeded with high site selectivity and excellent enantioselectivity (up to 99%) mediated by an Ir-(P, olefin) complex.

allylic alcohols

potassium alkenyltrifluoroborates

Ir-(P, olefin)


Input: This method allows rapid access to various 1, 4-dienes or trienes including the biologically active natural products (-)-nyasol and (-)-hinokiresinol.

1, 4-dienes

trienes

(-)-nyasol

(-)-hinokiresinol


Input: Can we delay the accelerated lung aging in COPD?


Input: Anti-aging molecules and interventions.


Input: Chronic obstructive pulmonary disease (COPD) has been recently characterized as a disease of accelerated lung aging.


Input: The prevalence of COPD is age-dependent suggesting an intimate relationship between the pathogenesis of COPD and aging.


Input: Lung function decline, the hallmark feature of COPD evolution, is more prominent with increasing age and this decline is greater in smoking individuals.


Input: One of the major goals of COPD pharmacotherapy is the development of drugs that would be able to result in a decrease of the decline in lung function over years.


Input: However, till nowadays smoking cessation is the only known intervention which is able to decelerate lung function decline.


Input: Several mechanisms of aging, including oxidative stress, inflammation and telomere shortening have been shown to be implicated in COPD.


Input: Furthermore, numerous anti-aging molecules, including sirtuins and Nrf-2 are reduced, and pathways such as mTOR and genes such as Klotho have also been shown to be abnormal in the lungs of COPD patients.


Input: The above mechanisms have been associated with the accelerated lung aging in COPD patients.


Input: Numerous therapeutic interventions have been studied in an attempt to reverse accelerated lung aging, and some of them have already been tested in clinical trials.


Input: The aim of the present review is to summarize the mechanisms associated with the accelerated lung aging in COPD and to provide information about the possible therapeutic implications targeting those mechanisms.


Input: Managing comorbidity in COPD: a difficult task.


Input: Chronic obstructive pulmonary disease is a public health problem that results in high morbidity, disability and mortality.


Input: Comorbidities are highly prevalent in COPD patients because of aging, common risk factors and pathways, rising mortality, and disability.


Input: In this review article we present the most prevalent co-morbidities in COPD patients, we face the issue of multimorbidity and discuss the practical management approach relevant to chest physicians and general practitioners.


Input: Issues on comorbidities management according to general guidelines as well as their implications for COPD are raised.


Input: The aim is to give clinicians an easy update with specific recommendations for each comorbidity.


Input: The implications of several medications used for comorbidities in COPD in terms of benefits, concerns, medication preference, medication avoidance and contraindications are also discussed.


Input: Stem cell therapy in chronic obstructive pulmonary disease.


Input: Seeking the prometheus effect.


Input: Chronic obstructive pulmonary disease is characterized by dramatic alterations in lung architecture associated to an exaggerated inflammatory process, alveolar epithelial cell apoptosis, endothelial dysfunction and extracellular matrix destruction due to a protease and anti-protease imbalance.


Input: In addition a significant inflammatory spillover into systemic circulation has been suggested to be responsible for a wide range of fatal comorbidities.


Input: In view of the current disappointing status of available pharmaceutical agents, there is an urgent need for alternative more effective therapeutic approaches that will fulfill the unmet need of modulating both local and systemic inflammation and at the same time accelerate alveolar epithelial and endothelial turnover intervening into disease natural course and not only relieving patient' s symptoms.


Input: Regenerative medicine based on stem cells properties represents one promising option with several fruitful therapeutic applications in patients with COPD.


Input: Nevertheless, despite relative enthusiasm arising from experimental data, application of stem cell therapy in the clinical setting has been severely hampered by several safety concerns arising from the major lack of knowledge on the fate of exogenously administrated stem cells within the COPD lung as well as the mechanisms regulating activation of resident progenitor cells.


Input: The above evidence coupled with the rather disappointing results emerging from the first stem cell clinical trials in COPD patients underline the need for careful study design by setting realistic goals to assess efficacy such as biomarkers that reflect clinically inconspicuous alterations of the disease molecular phenotype before rigid conclusions can be safely drawn.


Input: Novel modalities and agents in bronchoscopic lung volume reduction.


Input: The NETT study has shown the effectiveness of lung volume reduction surgery (LVRS) in improving functional parameters and exercise tolerance in selected patients with severe pulmonary emphysema of upper lobe predominance.


Input: A number of bronchoscopic techniques have since been developed under the term " bronchoscopic lung volume reduction " (BLVR), aiming to lower the complications and the cost while facilitating the procedure of lung volume approach in patients with emphysema.


Input: These include airway bypass by creation of airway/parenchyma communications, one-way endobronchial valves occluding the airways of the targeted lobes, endobronchial coils which mechanically contract the parenchyma, hot vapour ablation thermally destroying the targeted sites and sealant which fill the alveoli with polymer material.


Input: These methods are generally simple and safe, with a favourable complications profile, requiring less infrastructure and interventional experience than the open surgical approach.


Input: Bronchial valves have produced promising results in a very narrow phenotype of emphysema patients and have the major advantage of being reversible in their action.


Input: Parenchymal interventions at the cost of producing permanent effects and a transient inflammatory syndrome, may be effective in larger group of patients regardless of the fissure integrity and the presence of collateral ventilation.


Input: New, more extensive multicentre studies are underway which aim at better selection and stratification of patients in order to further evaluate the safety and effectiveness of these techniques, before wider use of this revolutionary approach for severe lung emphysema can be advocated.


Input: Steroid toxicity and detoxification in ascomycetous fungi.

Steroid


Input: In the last couple of decades fungal infections have become a significant clinical problem.


Input: A major interest into fungal steroid action has been provoked since research has proven that steroid hormones are toxic to fungi and affect the host/fungus relationship.

steroid

steroid


Input: Steroid hormones were found to differ in their antifungal activity in ascomycetous fungi Hortaea werneckii, Saccharomyces cerevisiae and Aspergillus oryzae.

Steroid


Input: Dehydroepiandrosterone was shown to be the strongest inhibitor of growth in all three varieties of fungi followed by androstenedione and testosterone.

androstenedione

testosterone


Input: For their protection, fungi use several mechanisms to lower the toxic effects of steroids.

steroids