Input: The present study examines the apoptosis-inducing activity and the underlying mechanism of action of cinobufagin in osteosarcoma (OS) cells.

cinobufagin


Input: Our results showed that cinobufagin potently inhibited the proliferation of U2OS, MG63 and SaOS-2 cells.

cinobufagin


Input: Significant increases in G2/M cell-cycle arrest and apoptosis in OS cells were also observed.


Input: The expression levels of several apoptotic proteins were assessed after cinobufagin treatment in U2OS cells.

cinobufagin


Input: Among them, xIAP, cIAP-1, survivin and Bcl-2 levels decreased remarkably, while the levels of Bax and cleaved-PARP increased.


Input: Furthermore, we validated the inhibition of GSK-3 beta/NF-kappa B signaling following cinobufagin treatment.

cinobufagin


Input: Western blots showed a decrease in nuclear p65 protein expression after exposure to different concentrations of cinobufagin, while the phosphorylation of GSK-3 beta was simultaneously increased.

cinobufagin


Input: Transduction with constitutively active forms of GSK-3 beta could protect against the downregulation of p65 and upregulation of cleaved-PARP that are induced by cinobufagin treatment.

cinobufagin


Input: However, combined treatment with cinobufagin and SB216367 resulted in a significant reduction in p65 and an increase in cleaved-PARP in U2OS cells.

cinobufagin


Input: Altogether, these results show that cinobufagin is a promising agent for the treatment of OS.

cinobufagin


Input: These studies are the first to reveal the involvement of the GSK-3 beta/NF-kappa B pathway in cinobufagin-induced apoptosis.

cinobufagin


Input: Pathophysiological roles of aldo-keto reductases (AKR1C1 and AKR1C3) in development of cisplatin resistance in human colon cancers.

cisplatin


Input: Cisplatin (cis-diamminedichloroplatinum, CDDP) is widely used for treatment of patients with solid tumors formed in various organs including the lung, prostate and cervix, but is much less sensitive in colon and breast cancers.

Cisplatin

cis-diamminedichloroplatinum

CDDP


Input: One major factor implicated in the ineffectiveness has been suggested to be acquisition of the CDDP resistance.

CDDP


Input: Here, we established the CDDP-resistant phenotypes of human colon HCT15 cells by continuously exposing them to incremental concentrations of the drug, and monitored expressions of aldo-keto reductases (AKRs) 1A1, 1B1, 1B10, 1C1, 1C2 and 1C3.

CDDP


Input: Among the six AKRs, AKR1C1 and AKR1C3 are highly induced with the CDDP resistance.

CDDP


Input: The resistance lowered the sensitivity toward cellular damages evoked by oxidative stress-derived aldehydes, 4-hydroxy-2-nonenal and 4-oxo-2-nonenal that are detoxified by AKR1C1 and AKR1C3.

aldehydes


Input: Overexpression of AKR1C1 or AKR1C3 in the parental HCT15 cells mitigated the cytotoxicity of the aldehydes and CDDP.

aldehydes

CDDP


Input: Knockdown of both AKR1C1 and AKR1C3 in the resistant cells or treatment of the cells with specific inhibitors of the AKRs increased the sensitivity to CDDP toxicity.

CDDP


Input: Thus, the two AKRs participate in the mechanism underlying the CDDP resistance probably via detoxification of the aldehydes resulting from enhanced oxidative stress.

CDDP

aldehydes


Input: The resistant cells also showed an enhancement in proteolytic activity of proteasome accompanied by overexpression of its catalytic subunits (PSM beta 9 and PSM beta 10).


Input: Pretreatment of the resistant cells with a potent proteasome inhibitor Z-Leu-Leu-Leu-al augmented the CDDP sensitization elicited by the AKR inhibitors.

Z-Leu-Leu-Leu-al

CDDP


Input: Additionally, the treatment of the cells with Z-Leu-Leu-Leu-al and the AKR inhibitors induced the expressions of the two AKRs and proteasome subunits.

Z-Leu-Leu-Leu-al


Input: Collectively, these results suggest the involvement of up-regulated AKR1C1, AKR1C3 and proteasome in CDDP resistance of colon cancers and support a chemotherapeutic role for their inhibitors.

CDDP


Input: Local structure and dynamics of benzene confined in the IRMOF-1 nanocavity as studied by molecular dynamics simulation.

benzene


Input: The local structure and dynamic behaviour of a benzene molecular assembly confined within the nano-cavities of a zinc-based metal-organic framework, [Zn (4) O (CO (2) C (6) H (4) CO (2)) (3)] (n) (IRMOF-1), were investigated by means of molecular dynamics (MD) simulations.

benzene

zinc

[Zn (4) O (CO (2) C (6) H (4) CO (2)) (3)] (n)


Input: The local structure of the confined benzene molecules was evaluated using radial distribution functions.

benzene


Input: The sites for adsorption of benzene in IRMOF-1 were well defined by the simulation.

benzene


Input: The diffusion coefficients at ambient temperature suggested that the mobility of the confined benzene was high, comparable to the bulk fluid.

benzene


Input: Decreasing the temperature gave rise to the aggregation of benzene in the IRMOF-1 frameworks.

benzene


Input: Molecular aggregation was attributed to the localization of benzene in the large and the small cavities of IRMOF-1, respectively.

benzene


Input: Both the translational diffusion coefficient and the trajectory of benzene provided evidence that the localization of benzene in the large and the small cavities takes place at ca.

benzene

benzene


Input: 200 K.


Input: Furthermore, at high benzene loading, the migration of benzene in the small cavities was prevented (frozen) below 135 K.

benzene

benzene


Input: Thus, the translational degree of freedom of the benzene molecules changed drastically, depending on the temperature.

benzene


Input: Computer simulation study of nanoparticle interaction with a lipid membrane under mechanical stress.


Input: Pore formation of lipid bilayers under mechanical stress is critical to biological processes.


Input: A series of coarse grained molecular dynamics simulations of lipid bilayers with carbon nanoparticles different in size have been performed.

carbon


Input: Surface tension was applied to study the disruption of lipid bilayers by nanoparticles and the formation of pores inside the bilayers.


Input: The presence of small nanoparticles enhances the probability of water penetration thus decreasing the membrane rupture tension, while big nanoparticles have the opposite effect.


Input: Nanoparticle volume affects bilayer strength indirectly, and particle surface density can complicate the interaction.


Input: The structural, dynamic, elastic properties and lateral densities of lipid bilayers with nanoparticles under mechanical stress were analyzed.


Input: The results demonstrate the ability of nanoparticles to adjust the structural and dynamic properties of a lipid membrane, and to efficiently regulate the pore formation behavior and hydrophobicity of membranes.


Input: Development of automated paper-based devices for sequential multistep sandwich enzyme-linked immunosorbent assays using inkjet printing.


Input: To the best of our knowledge, this is the first report on paper-based devices for automating the sequential multistep procedures of a sandwich-type enzyme-linked immunosorbent assay (ELISA) that require only a single-step application of the sample solution.


Input: The device was based on a piece of nitrocellulose (NC) membrane with specially designed channels, where all the reagents are applied at different locations in order to control the fluid travel to the detection region.


Input: The inkjet printing method, a simple and low-cost process, was used to create the flow channel and device barrier patterns.


Input: The fabricated barrier was found to be an efficient boundary for the liquid along the printed design in the NC membrane, enabling direct control of the reagent flow time.


Input: ELISA results were obtained with a single-step sample application.


Input: The developed devices (so-called automated paper-based devices) provided a simple procedure for the sandwich ELISA, while reducing assay time and reagent consumption.


Input: Colorimetric results were measured using digital camera imaging with software processing.


Input: The capability of the method developed herein was successfully used to determine the levels of human chorionic gonadotropin (hCG) by ELISA.


Input: A VUV photoionization study of the multichannel reaction of phenyl radicals with 1, 3-butadiene under combustion relevant conditions.

phenyl

1, 3-butadiene


Input: We studied the reaction of phenyl radicals (C (6) H (5)) with 1, 3-butadiene (H (2) CCHCHCH (2)) exploiting a high temperature chemical reactor under combustion-like conditions (300 Torr, 873 K).

phenyl

C (6) H (5)

1, 3-butadiene

H (2) CCHCHCH (2)


Input: The reaction products were probed in a supersonic beam by utilizing VUV radiation from the Advanced Light Source and by recording the experimental PIE curves at mass-to-charge ratios of m/z = 130 (C (10) H (10) (+)), 116 (C (9) H (8) (+)), and 104 (C (8) H (8) (+)).

C (10) H (10) (+)

C (9) H (8) (+)

C (8) H (8) (+)


Input: Our data suggest that the atomic hydrogen (H), methyl (CH (3)), and vinyl (C (2) H (3)) losses are open with estimated branching ratios of about 86 +/- 4%, 8 +/- 2%, and 6 +/- 2%, respectively.

hydrogen

H

methyl

CH (3)

vinyl

C (2) H (3)


Input: The isomer distributions were probed further by fitting the experimentally recorded PIE curves with a linear combination of the PIE curves of individual C (10) H (10), C (9) H (8), and C (8) H (8) isomers.

C (10) H (10)

C (9) H (8)

C (8) H (8)


Input: These fits indicate the formation of three C (10) H (10) isomers (trans-1, 3-butadienylbenzene, 1, 4-dihydronaphthalene, 1-methylindene), three C (9) H (8) isomers (indene, phenylallene, 1-phenyl-1-methylacetylene), and a C (8) H (8) isomer (styrene).

C (10) H (10)

trans-1, 3-butadienylbenzene

1, 4-dihydronaphthalene

C (9) H (8)

indene

phenylallene

C (8) H (8)

styrene


Input: A comparison with results from recent crossed molecular beam studies of the 1, 3-butadiene-phenyl radical reaction and electronic structure calculations suggests that trans-1, 3-butadienylbenzene (130 amu), 1, 4-dihydronaphthalene (130 amu), and styrene (104 amu) are reaction products formed as a consequence of a bimolecular reaction between the phenyl radical and 1, 3-butadiene.

1, 3-butadiene-phenyl

trans-1, 3-butadienylbenzene

1, 4-dihydronaphthalene

styrene

phenyl

1, 3-butadiene


Input: 1-Methylindene (130 amu), indene (116 amu), phenylallene (116 amu), and 1-phenyl-1-methylacetylene (116 amu) are synthesized upon reaction of the phenyl radical with three C (4) H (6) isomers: 1, 2-butadiene (H (2) CCCH (CH (3))), 1-butyne (HCCC (2) H (5)), and 2-butyne (CH (3) CCCH (3)); these C (4) H (6) isomers can be formed from 1, 3-butadiene via hydrogen atom assisted isomerization reactions or via thermal rearrangements of 1, 3-butadiene involving hydrogen shifts in the high temperature chemical reactor.

indene

phenylallene

phenyl

C (4) H (6)

1, 2-butadiene

H (2) CCCH (CH (3))

HCCC (2) H (5)

CH (3) CCCH (3)

C (4) H (6)

1, 3-butadiene

hydrogen

1, 3-butadiene

hydrogen


Input: EphB4 enhances the process of endochondral ossification and inhibits remodeling during bone fracture repair.


Input: Previous reports have identified a role for the tyrosine kinase receptor EphB4 and its ligand, ephrinB2, as potential mediators of both bone formation by osteoblasts and bone resorption by osteoclasts.

tyrosine


Input: In the present study, we examined the role of EphB4 during bone repair after traumatic injury.


Input: We performed femoral fractures with internal fixation in transgenic mice that overexpress EphB4 under the collagen type 1 promoter (Col1-EphB4) and investigated the bone repair process up to 12 weeks postfracture.


Input: The data indicated that Col1-EphB4 mice exhibited stiffer and stronger bones after fracture compared with wild-type mice.


Input: The fractured bones of Col1-EphB4 transgenic mice displayed significantly greater tissue and bone volume 2 weeks postfracture compared with that of wild-type mice.


Input: These findings correlated with increased chondrogenesis and mineral formation within the callus site at 2 weeks postfracture, as demonstrated by increased safranin O and von Kossa staining, respectively.

safranin O


Input: Interestingly, Col1-EphB4 mice were found to possess significantly greater numbers of clonogenic mesenchymal stromal progenitor cells (CFU-F), with an increased capacity to form mineralized nodules in vitro under osteogenic conditions, when compared with those of the wild-type control mice.


Input: Furthermore, Col1-EphB4 mice had significantly lower numbers of TRAP-positive multinucleated osteoclasts within the callus site.


Input: Taken together, these observations suggest that EphB4 promotes endochondral ossification while inhibiting osteoclast development during callus formation and may represent a novel drug target for the repair of fractured bones.


Input: Compartmentalization and antiviral effect of efavirenz metabolites in blood plasma, seminal plasma, and cerebrospinal fluid.

efavirenz


Input: Efavirenz (EFV) is one of the most commonly prescribed antiretrovirals for use in the treatment of human immunodeficiency virus (HIV) infection.

Efavirenz

EFV


Input: EFV is extensively metabolized by cytochrome P450 to a number of oxygenated products; however, the pharmacologic activity and distribution of these metabolites in anatomic compartments have yet to be explored.

EFV


Input: The systemic distribution of EFV oxidative metabolites was examined in blood plasma, seminal plasma, and cerebrospinal fluid from subjects on an EFV-based regimen.

EFV

EFV


Input: The 8-hydroxy EFV metabolite was detected in blood plasma, seminal plasma, and cerebrospinal fluid, with median concentrations of 314. 5 ng/ml, 358. 5 ng/ml, and 3. 37 ng/ml, respectively.

8-hydroxy EFV


Input: In contrast, 7-hydroxy and 8, 14-hydroxy EFV were only detected in blood plasma and seminal plasma with median concentrations of 8. 84 ng/ml and 10. 23 ng/ml, and 5. 63 ng/ml and 5. 43 ng/ml, respectively.

7-hydroxy and 8, 14-hydroxy EFV


Input: Interestingly, protein-free concentrations of metabolites were only detectable in seminal plasma, where a novel dihdyroxylated metabolite of EFV was also detected.

EFV


Input: This accumulation of protein-free EFV metabolites was demonstrated to be the result of differential protein binding in seminal plasma compared with that of blood plasma.

EFV


Input: In addition, the oxidative metabolites of EFV did not present with any significant pharmacologic activity toward HIV-1 as measured using an HIV green fluorescent protein single-round infectivity assay.

EFV


Input: This study is the first to report the physiologic distribution of metabolites of an antiretroviral into biologic compartments that the virus is known to distribute and to examine their anti-HIV activity.


Input: These data suggest that the male genital tract may be a novel compartment that should be considered in the evaluation of drug metabolite exposure.


Input: Molecular interaction studies of HIV-1 matrix protein p17 and heparin: identification of the heparin-binding motif of p17 as a target for the development of multitarget antagonists.


Input: Once released by HIV (+) cells, p17 binds heparan sulfate proteoglycans (HSPGs) and CXCR1 on leukocytes causing their dysfunction.

sulfate


Input: By exploiting an approach integrating computational modeling, site-directed mutagenesis of p17, chemical desulfation of heparin, and surface plasmon resonance, we characterized the interaction of p17 with heparin, a HSPG structural analog, and CXCR1.


Input: p17 binds to heparin with an affinity (K (d) = 190 nm) that is similar to those of other heparin-binding viral proteins.


Input: Two stretches of basic amino acids (basic motifs) are present in p17 N and C termini.

amino acids

N

C


Input: Neutralization (Arg --> Ala substitution) of the N-terminal, but not of the C-terminal basic motif, causes the loss of p17 heparin-binding capacity.

Arg

Ala

N

C


Input: The N-terminal heparin-binding motif of p17 partially overlaps the CXCR1-binding domain.

N


Input: Accordingly, its neutralization prevents also p17 binding to the chemochine receptor.


Input: Competition experiments demonstrated that free heparin and heparan sulfate (HS), but not selectively 2-O-, 6-O-, and N-O desulfated heparins, prevent p17 binding to substrate-immobilized heparin, indicating that the sulfate groups of the glycosaminoglycan mediate p17 interaction.

sulfate

O

O

N-O


Input: Evaluation of the p17 antagonist activity of a panel of biotechnological heparins derived by chemical sulfation of the Escherichia coli K5 polysaccharide revealed that the highly N, O-sulfated derivative prevents the binding of p17 to both heparin and CXCR1, thus inhibiting p17-driven chemotactic migration of human monocytes with an efficiency that is higher than those of heparin and HS.

N

O


Input: Here, we characterized at a molecular level the interaction of p17 with its cellular receptors, laying the basis for the development of heparin-mimicking p17 antagonists.


Input: Insight into tissue unbound concentration: utility in drug discovery and development.


Input: In a preclinical setting, plasma or whole tissue drug concentrations are often correlated with pharmacodynamics, although according to the free drug hypothesis, unbound drug concentration should be more pharmacologically relevant.


Input: Alternatively, blood concentrations may be a good surrogate for tissue concentration for passively permeable compounds.


Input: However, for a large number of compounds that are substrates for uptake and/or efflux transporters expressed at the tissue level, significant discrepancies are expected between unbound concentrations in blood and those in tissues.


Input: Consequently, attempts have been made to measure tissue unbound drug concentrations using tissue homogenates, slices and microdialysis.


Input: Mathematical expressions for calculating the rate and extent of drug distribution into tissues have also been established.


Input: For example, a ratio of unbound concentration in the tissue to that in plasma (K (p, uu)) is the best indicator of the extent of tissue distribution.


Input: Despite these technical advances, however, very few examples demonstrate a focus on tissue unbound drug concentrations in a preclinical setting.


Input: This review will illustrate various techniques to estimate tissue unbound drug concentrations, relevant parameters to calculate the rate and extent of tissue distribution and different factors affecting tissue unbound concentration.


Input: The review will also highlight various examples from the literature where tissue unbound drug concentrations have demonstrated a superior correlation with efficacy.


Input: The impact of tissue unbound drug concentrations on the projection of human efficacious dose is also discussed.


Input: Positive allosteric modulator of alpha 7 nicotinic-acetylcholine receptors, PNU-120596 augments the effects of donepezil on learning and memory in aged rodents and non-human primates.

acetylcholine

donepezil


Input: The development of novel therapeutic agents for disorders of cognition such as Alzheimer' s disease (AD) is of paramount importance given the ever-increasing elderly population, however; there is also considerable interest in any strategy that might enhance the clinical efficacy of currently available treatments.


Input: The purpose of this study was to evaluate an adjunctive treatment strategy to memory enhancement, namely combining the commonly prescribed acetylcholinesterase inhibitor (AChEI) donepezil, with a positive allosteric modulator (PAM) of alpha 7 nicotinic-acetylcholine receptors (alpha 7-nAChRs), PNU-120596.

donepezil

acetylcholine


Input: The treatment strategy was evaluated in a (non-spatial) spontaneous novel object recognition (NOR) task in young rats; a water maze spatial learning and recall procedure in aged, cognitively-impaired rats, and a delayed match to sample (working/short term memory) task in aged rhesus monkeys.


Input: In all three experiments a similar drug response was observed, namely that donepezil administered alone improved task performance in a dose-dependent manner; that PNU-120596 administered alone was without significant effect, but that the combination of PNU-120596 with a subthreshold dose of donepezil was effective.

donepezil

donepezil


Input: The positive effect of the drug combination appeared to be alpha 7-nAChR mediated given that it was blocked in the NOR task by the selective alpha 7-nAChR antagonist methyllycaconitine (MLA).

methyllycaconitine

MLA


Input: Collectively, these data indicate that PNU-120596 increases the effective dose range of donepezil in learning/memory-related tasks in young and age-impaired animal models.

donepezil


Input: The results suggest that alpha 7-nAChR-selective PAMs like PNU-120596 have potential as adjunctive treatments with acetylcholinesterase inhibitors (e. g., donepezil) for age-related illnesses such as AD as well memory disorders not necessarily associated with advanced age.

donepezil


Input: 1H NMR spectra of ethane-1, 2-diol and other vicinal diols in benzene: GIAO/DFT shift calculations.

ethane-1, 2-diol

vicinal diols

benzene


Input: The proton NMR spectra of several 1, 2-diols in benzene have been analysed so as to associate each magnetically nonequivalent proton with its chemical shift.

1, 2-diols

benzene


Input: The shifts and coupling constants of the OH and methylene protons of ethane-1, 2-diol have been determined in a wide range of solvents.

OH

methylene

ethane-1, 2-diol


Input: The conformer distribution and the proton NMR shifts of these 1, 2-diols in benzene have been computed on the basis of density functional theory.

1, 2-diols

benzene


Input: The solvent is included using the integral-equation-formalism polarizable continuum model implemented in Gaussian 09.


Input: Relative Gibbs energies for all stable conformers are calculated at the Perdew, Burke and Enzerhof (PBE) 0/6-311 + G (d, p) level, and shifts are calculated using the gauge-including atomic orbital method with the PBE0/6-311 + G (d, p) geometry but using the cc-pVTZ basis set.


Input: Previous calculations on ethane-1, 2-diol and propane-1, 2-diol have been corrected and extended.

ethane-1, 2-diol

propane-1, 2-diol


Input: New calculations on tert-butylethane-1, 2-diol, phenylethane-1, 2-diol, butane-2, 3-diols (dl and meso) and cyclohexane-1, 2-diols (cis and trans) are presented.

tert-butylethane-1, 2-diol

phenylethane-1, 2-diol

butane-2, 3-diols

cyclohexane-1, 2-diols


Input: Overall, the computed NMR shifts are in good agreement with experimental values for the OH protons but remain systematically high for CH protons.

OH

CH


Input: Some results based on the Gaussian 03 solvation model are included for comparison.


Input: Discovery of Schaeffer' s acid analogues as lead structures of mycobacterium tuberculosis type II dehydroquinase using a rational drug design approach.

Schaeffer' s acid


Input: Rational ligand design: Schaeffer' s acid analogues were identified as novel inhibitors of M. tuberculosis type II dehydroquinase, a key enzyme of the shikimate pathway.

Schaeffer' s acid


Input: Their likely binding mode was predicted using a combination of ensemble docking and flexible active site residues.


Input: Potentially, this scaffold could provide a good starting point for the design of antitubercular agents.


Input: Stem cell-mediated gene delivering for the treatment of cerebral ischemia: progress and prospectives.


Input: Ischemic stroke is one of the leading causes of death and disability worldwide.


Input: There is no effective treatment for ischemic stroke apart from thrombolytic therapy, which has a narrow therapeutic time window.


Input: Gene therapy has proven to be effective in experimental stroke, but it suffers from disadvantages that limit its clinical application, such as difficulty in intracranial delivering of therapeutic genes, low efficacy in transfecting host cells and long-term expression of exogenous genes.


Input: Delivering therapeutic genes to the ischemic brain via stem cells is an alternative strategy of combined gene and stem cell therapy.


Input: There are advantages for stem cell-mediated gene delivery as opposed to direct gene transfer.


Input: In recent years, studies used stem cells that over-express different neurotrophic factors, such as BDNF, GDNT, or NT3, and found that the delivery of these genetically-modified stem cells to animal models of ischemic stroke is safe and effective, thus suggesting that stem cell-based gene therapy may be a promising treatment for stroke.


Input: This review summarizes the advantages and recent progress of stem cell-based gene therapy for ischemic stroke.


Input: We also discuss the relevant strategy for optimizing stem cell-based gene therapy and discuss the potential strategies for its future application.


Input: Structure Based Lead Optimization Approach in Discovery of Selective DPP4 Inhibitors.


Input: Diabetes mellitus is a chronic progressive metabolic disorder that has profound consequences for individuals, families, and society.


Input: To date, main available oral antidiabetic medications target either insulin resistance (metformin, glitazones), or insulin deficiency (sulfonylureas, glinides), but leading to shortfalls in medication.

metformin

glitazones

sulfonylureas

glinides


Input: Advancement in modern oral hypoglycemic agents may be encouraged with or in place of traditional therapies.


Input: The lower risk for hypoglycemic events as compared with other insulinotropic or insulin-sensitizing agents make DPP-4 inhibitors very promising candidates for a more physiological treatment of type-2 diabetes.


Input: Only some DPP-4 inhibitors are currently used for the treatment of type 2 diabetes (T2DM) and various inhibitors currently undergoing animal and human testing.


Input: A number of catalytically active DPPs distinct from DPP-4 (DPP II, FAP, DPP-8, and DPP-9) have been described that is associated with side-effect and toxicity.


Input: To discover potent and selective and safer drugs in a shorter time frame and with reduced cost it requires using an innovative approach for designing novel inhibitors.


Input: This review article focuses on the status of advanced lead candidates of DPP group and their binding affinity with the active site residue of target structure which help in discovery of potent and selective DPP-4 inhibitors by lead optimization approach.


Input: Metabolomics and mass isotopomer analysis as a strategy for pathway discovery: pyrrolyl and cyclopentenyl derivatives of the pro-drug of abuse, levulinate.

pyrrolyl

cyclopentenyl

levulinate


Input: We recently reported that levulinate (4-ketopentanoate) is converted in the liver to 4-hydroxypentanoate, a drug of abuse, and that the formation of 4-hydroxypentanoate is stimulated by ethanol oxidation.

levulinate

ethanol


Input: We also identified 3 parallel beta-oxidation pathways by which levulinate and 4-hydroxypentanoate are catabolized to propionyl-CoA and acetyl-CoA.

levulinate

propionyl-CoA

acetyl-CoA


Input: We now report that levulinate forms three seven-carbon cyclical CoA esters by processes starting with the elongation of levulinyl-CoA by acetyl-CoA to 3, 6-diketoheptanoyl-CoA.

levulinate

carbon

levulinyl-CoA

acetyl-CoA

3, 6-diketoheptanoyl-CoA


Input: The latter gamma-diketo CoA ester undergoes two parallel cyclization processes.

gamma-diketo CoA ester


Input: One process yields a mixture of tautomers, i. e., cyclopentenyl-and cyclopentadienyl-acyl-CoAs.

cyclopentenyl-and cyclopentadienyl-acyl-CoAs


Input: The second cyclization process yields a methyl-pyrrolyl-acetyl-CoA containing a nitrogen atom derived from the epsilon-nitrogen of lysine but without carbons from lysine.

methyl-pyrrolyl-acetyl-CoA

nitrogen

epsilon-nitrogen

lysine

carbons

lysine


Input: The cyclic CoA esters were identified in rat livers perfused with levulinate and in livers and brains from rats gavaged with calcium levulinate +/- ethanol.

cyclic CoA esters

levulinate

calcium levulinate

ethanol


Input: Lastly, 3, 6-diketoheptanoyl-CoA, like 2, 5-diketohexane, pyrrolates free lysine and, presumably, lysine residues from proteins.

3, 6-diketoheptanoyl-CoA

2, 5-diketohexane

pyrrolates

lysine

lysine


Input: This may represent a new pathway for protein pyrrolation.


Input: The cyclic CoA esters and related pyrrolation processes may play a role in the toxic effects of 4-hydroxypentanoate.

cyclic CoA esters


Input: The evolution of north-east Atlantic gadfly petrels using statistical phylogeography.


Input: Macaronesia (north-east Atlantic archipelagos) has been host to complex patterns of colonization and differentiation in many groups of organisms including seabirds such as gadfly petrels (genus Pterodroma).


Input: Considering the subspecies of widely distributed soft-plumaged petrel for many years, the taxonomic status of the three gadfly petrel taxa breeding in Macaronesia is not yet settled, some authors advocating the presence of three, two or one species.


Input: These birds have already been the subject of genetic studies with only one mtDNA gene and relatively modest sample sizes.


Input: In this study, using a total of five genes (two mitochondrial genes and three nuclear introns), we investigated the population and phylogeographical histories of petrel populations breeding on Madeira and Cape Verde archipelagos.


Input: Despite confirming complete lineage sorting with mtDNA, analyses with nucDNA failed to reveal any population structuring and Isolation with Migration analysis revealed the absence of gene flow during the differentiation process of these populations.


Input: It appears that the three populations diverged in the late Pleistocene in the last 150 000 years, that is 10 times more recently than previous estimates based solely on one mtDNA gene.


Input: Finally, our results suggest that the Madeira petrel population is ancestral rather than that from Cape Verde.


Input: This study strongly advocates the use of nuclear loci in addition to mtDNA in demographical and phylogeographical history studies.


Input: WDDD: Worm Developmental Dynamics Database.


Input: During animal development, cells undergo dynamic changes in position and gene expression.


Input: A collection of quantitative information about morphological dynamics under a wide variety of gene perturbations would provide a rich resource for understanding the molecular mechanisms of development.


Input: Here, we created a database, the Worm Developmental Dynamics Database (http://so. qbic. riken. jp/wddd/), which stores a collection of quantitative information about cell division dynamics in early Caenorhabditis elegans embryos with single genes silenced by RNA-mediated interference.


Input: The information contains the three-dimensional coordinate values of the outlines of nuclear regions and the dynamics of the outlines over time.


Input: The database provides free access to 50 sets of quantitative data for wild-type embryos and 136 sets of quantitative data for RNA-mediated interference embryos corresponding to 72 of the 97 essential embryonic genes on chromosome III.


Input: The database also provides sets of four-dimensional differential interference contrast microscopy images on which the quantitative data were based.


Input: The database will provide a novel opportunity for the development of computational methods to obtain fresh insights into the mechanisms of development.


Input: The quantitative information and microscopy images can be synchronously viewed through a web browser, which is designed for easy access by experimental biologists.


Input: Atomically flat, large-sized, two-dimensional organic nanocrystals.


Input: Large-sized, 2D single crystals of perylene are grown by both solution-cast and physical vapor transport methods.

perylene


Input: The crystals have a atomically flat parallelogram morphology and the aspect ratios of the lateral extension compared to the thickness are up to 10 (3).


Input: The atomically flat feature leads to good interface contact, making a single-crystal field-effect transistor with higher mobility.


Input: The mobility of atomically flat crystals can be 10 (3)-10 (4) times higher than rough crystals.


Input: 3D-QSAR-assisted drug design: identification of a potent quinazoline-based Aurora kinase inhibitor.

quinazoline


Input: We describe the 3D-QSAR-assisted design of an Aurora kinase A inhibitor with improved physicochemical properties, in vitro activity, and in vivo pharmacokinetic profiles over those of the initial lead.


Input: Three different 3D-QSAR models were built and validated by using a set of 66 pyrazole (Model I) and furanopyrimidine (Model II) compounds with IC (50) values toward Aurora kinase A ranging from 33 nM to 10. 5 mu M.

pyrazole

furanopyrimidine


Input: The best 3D-QSAR model, Model III, constructed with 24 training set compounds from both series, showed robustness (r (2) (CV) = 0. 54 and 0. 52 for CoMFA and CoMSIA, respectively) and superior predictive capacity for 42 test set compounds (R (2) (pred) = 0. 52 and 0. 67, CoMFA and CoMSIA).


Input: Superimposition of CoMFA and CoMSIA Model III over the crystal structure of Aurora kinase A suggests the potential to improve the activity of the ligands by decreasing the steric clash with Val147 and Leu139 and by increasing hydrophobic contact with Leu139 and Gly216 residues in the solvent-exposed region of the enzyme.


Input: Based on these suggestions, the rational redesign of furanopyrimidine 24 (clog P = 7. 41; Aurora A IC (50) = 43 nM; HCT-116 IC (50) = 400 nM) led to the identification of quinazoline 67 (clog P = 5. 28; Aurora A IC (50) = 25 nM; HCT-116 IC (50) = 23 nM).

furanopyrimidine

quinazoline


Input: Rat in vivo pharmacokinetic studies showed that 67 has better systemic exposure after i. v. administration than 24, and holds potential for further development.


Input: Assessing the potential effectiveness of food and beverage taxes and subsidies for improving public health: a systematic review of prices, demand and body weight outcomes.


Input: Taxes and subsidies are increasingly being considered as potential policy instruments to incentivize consumers to improve their food and beverage consumption patterns and related health outcomes.


Input: This study provided a systematic review of recent U. S. studies on the price elasticity of demand for sugar-sweetened beverages (SSBs), fast food, and fruits and vegetables, as well as the direct associations of prices/taxes with body weight outcomes.

sugar


Input: Based on the recent literature, the price elasticity of demand for SSBs, fast food, fruits and vegetables was estimated to be-1. 21,-0. 52,-0. 49 and-0. 48, respectively.


Input: The studies that linked soda taxes to weight outcomes showed minimal impacts on weight; however, they were based on existing state-level sales taxes that were relatively low.


Input: Higher fast-food prices were associated with lower weight outcomes particularly among adolescents, suggesting that raising prices would potentially impact weight outcomes.


Input: Lower fruit and vegetable prices were generally found to be associated with lower body weight outcomes among both low-income children and adults, suggesting that subsidies that would reduce the cost of fruits and vegetables for lower-socioeconomic populations may be effective in reducing obesity.


Input: Pricing instruments should continue to be considered and evaluated as potential policy instruments to address public health risks.


Input: Cannabinoid agonists increase the interaction between beta-Arrestin 2 and ERK1/2 and upregulate beta-Arrestin 2 and 5-HT (2A) receptors.


Input: We have recently reported that selective cannabinoid 2 (CB (2)) receptor agonists upregulate 5-HT (2A) receptors by enhancing ERK1/2 signaling in prefrontal cortex (PFCx).


Input: Increased activity of cortical 5-HT (2A) receptors has been associated with several neuropsychiatric disorders such as anxiety and schizophrenia.


Input: Here we examine the mechanisms involved in this enhanced ERK1/2 activation in rat PFCx and in a neuronal cell model.


Input: Sprague-Dawley rats treated with a non-selective cannabinoid agonist (CP55940, 50 mu g/kg, 7 days, i. p.) showed enhanced co-immunoprecipitation of beta-Arrestin 2 and ERK1/2, enhanced pERK protein levels, and enhanced expression of beta-Arrestin 2 mRNA and protein levels in PFCx.


Input: In a neuronal cell line, we found that selective CB (2) receptor agonists upregulate beta-Arrestin 2, an effect that was prevented by selective CB (2) receptor antagonist JTE-907 and CB (2) shRNA lentiviral particles.


Input: Additionally, inhibition of clathrin-mediated endocytosis, ERK1/2, and the AP-1 transcription factor also prevented the cannabinoid receptor-induced upregulation of beta-Arrestin 2.


Input: Our results suggest that sustained activation of CB (2) receptors would enhance beta-Arrestin 2 expression possibly contributing to its increased interaction with ERK1/2, thereby driving the upregulation of 5-HT (2A) receptors.


Input: The CB (2) receptor-mediated upregulation of beta-Arrestin 2 would be mediated, at least in part, by an ERK1/2-dependent activation of AP-1.


Input: These data could provide the rationale for some of the adverse effects associated with repeated cannabinoid exposure and shed light on some CB (2) receptor agonists that could represent an alternative therapeutic because of their minimal effect on serotonergic neurotransmission.


Input: Beneficial effects of polyphenols on cardiovascular disease.

polyphenols


Input: In recent years, numerous studies have demonstrated the health benefits of polyphenols, and special attention has been paid to their beneficial effects against cardiovascular disease, the leading cause of death in the world today.

polyphenols


Input: Polyphenols present vasodilator effects and are able to improve lipid profiles and attenuate the oxidation of low density lipoproteins.

Polyphenols


Input: In addition, they present clear anti-inflammatory effects and can modulate apoptotic processes in the vascular endothelium.


Input: It has been suggested that most of these effects are a consequence of the antioxidant properties of polyphenols, but this idea is not completely accepted, and many other mechanisms have been proposed recently to explain the health effects of these compounds.

polyphenols


Input: In fact, different signaling pathways have been linked to polyphenols.

polyphenols


Input: This review brings together some recent studies which establish the beneficial properties of polyphenols for cardiovascular disease and analyzes the mechanisms involved in these properties.

polyphenols


Input: Deficits in male sexual behavior in adulthood after social instability stress in adolescence in rats.


Input: There is increasing evidence that exposure to stressors in adolescence has long-lasting effects on emotional and cognitive behavior, but little is known as to whether reproductive functions are affected.


Input: We investigated appetitive and consummatory aspects of sexual behavior in male rats that were exposed to chronic social instability stress (SS, n = 24) for 16 days in mid-adolescence compared to control rats (CTL, n = 24).


Input: Over five sexual behavior test sessions with a receptive female, SS rats made fewer ejaculations (p = 0. 02) and had longer latencies to ejaculation (p = 0. 03).


Input: When only data from rats that ejaculated in the fifth session were analyzed, SS rats (n = 18) had reduced copulatory efficiency (more mounts and intromissions before ejaculation) compared to CTL rats (n = 19) (p = 0. 004), and CTL rats were twice as likely as SS rats to make more than one ejaculation in the fifth session (p = 0. 05).


Input: Further, more CTL (14/24) than SS (5/25) rats ejaculated in four or more sessions (p = 0. 05).


Input: SS rats had lower plasma testosterone concentrations than CTL rats (p = 0. 05), but did not differ in androgen receptor, estrogen receptor alpha, or Fos immunoreactive cell counts in the medial preoptic area.

testosterone

androgen

estrogen


Input: The groups did not differ in a partner preference test administered between the fourth and fifth sexual behavior session.


Input: The results suggest that developmental history contributes to individual differences in reproductive behavior, and that stress exposures in adolescence may be a factor in sexual sluggishness.


Input: Angiotensin AT2 receptor activates the cyclic-AMP signaling pathway in eel.

cyclic-AMP


Input: A unique angiotensin type 2 receptor (AT2) that induces a cAMP signaling pathway was cloned and characterized for the first time in fish, Anguilla japonica.

cAMP


Input: Phylogeny and synteny results showed that the AT2s among fishes and tetrapods share the same origin despite a sub-cluster formation among eel, salmon, and zebrafish.


Input: The eel AT2 was expressed abundantly in the spleen and localized at straight arterioles and ellipsoid regions prior to the sinusoid, suggesting a role in the regulation of microcirculation and/or immune response.


Input: Various angiotensin (Ang) peptides, including Ang II, Ang III, and Ang IV, were detected in the spleen by a radioimmunoassay coupled with HPLC separation, and these endogenous peptides stimulated a cAMP signaling, which has no crosstalk with cGMP pathway.

cAMP

cGMP


Input: The common and contrasting features of AT2 between fishes and mammals imply some ancestral characters of AT2, which are important information for receptor binding and evolutionary studies.


Input: Intraindividual and interindividual variabilities in endogenous cortisol 6 beta-hydroxylation clearance as an index for in vivo CYP3A phenotyping in humans.

cortisol


Input: This study was designed to evaluate the in vivo activity of cytochrome P450 3A (CYP3A) in 49 healthy Japanese subjects aged 22-58 years using endogenous cortisol 6 beta-hydroxylation clearance [CLm (6 beta)], a novel biomarker for CYP3A phenotyping.

cortisol


Input: CLm (6 beta) in the 49 healthy subjects was 2. 40 +/- 0. 79 ml/min with an approximately 4-fold interindividual variability of CYP3A activity.


Input: The mean clearance in the 24 women was 2. 50 +/- 0. 89 ml/min; the value in the women was higher than in the 25 men (2. 30 +/- 0. 69 ml/min) by approximately 9%.


Input: We also measured the change of CLm (6 beta) in 14 healthy subjects in the morning at 10: 00-12: 00 every 2 or 3 days over a period of 36-53 days and observed a 1. 5-fold to 3. 4-fold day-to-day intraindividual variability in the CYP3A activity.


Input: The mean value for CLm (6 beta) in each subject for 36-53 days was 2. 54 +/- 0. 76 ml/min (n = 14).


Input: We also evaluated the CLm (6 beta) every 2 hours from 8: 00-20: 00 in 26 healthy subjects.


Input: The within-day intraindividual clearance variability was 1. 1-fold to 2. 5-fold (2. 45 +/- 0. 91 ml/min, n = 26).


Input: No characteristic diurnal rhythms were observed in the in vivo activity of CYP3A.


Input: Chemotherapy of leishmaniasis part X: synthesis and bioevaluation of novel terpenyl heterocycles.

terpenyl heterocycles


Input: Some novel alpha and beta ionone based chalcones and their dihydropyrazolidines/pyrazolidines have been synthesized and evaluated for their in vitro and in vivo antileishmanial activities against Leishmania donovani.

alpha and beta ionone

chalcones

dihydropyrazolidines

pyrazolidines


Input: Amongest all, one compound (4d) exhibited significant in vitro activity against intracellular amastigotes of Leishmania donovani with IC (50) values of 7. 49 mu M and was found promising as compared to reference drug, miltefosine.

miltefosine


Input: On the basis of good Selectivity Index (S. I.), the compound was further tested for its in vivo response against Leishmania donovani/hamster model and has shown significant inhibition of parasite multiplication (81%).


Input: The present study has helped us in identifying a new lead that could be exploited as a potential antileishmanial agent.


Input: Design, synthesis and inhibitory activities of naringenin derivatives on human colon cancer cells.

naringenin


Input: Based on the previous result, several naringenin derivatives modified at position 7 with bulky substituents were designed and synthesized, and their inhibitory effects on HCT116 human colon cancer cells were tested using a clonogenic assay.

naringenin


Input: The half maximal inhibitory concentrations (IC (50)) of five naringenin derivatives ranged between 1. 20 mu M and 20. 01 mu M which are much better than naringenin used as a control.

naringenin

naringenin


Input: In addition, new structural modification at C-4 of flavanone results in improving both the anti-cancer effect and anti-oxidative effect.

flavanone


Input: In vitro cyclin dependent kinase 2 (CDK2) binding assay was carried out based on the previous results.


Input: To elucidate the possible interaction between naringenin derivatives and CDK2, in silico docking study was performed.

naringenin


Input: This result demonstrates the rationale for the different inhibitory activities of the naringenin derivatives.

naringenin


Input: These findings could be used for designing cancer therapeutic or preventive flavanone-derived agents.

flavanone


Input: Triazoyl-phenyl linker system enhancing the aqueous solubility of a molecular probe and its efficiency in affinity labeling of a target protein for jasmonate glucoside.

Triazoyl-phenyl

jasmonate glucoside


Input: In methods employing molecular probes to explore the targets of bioactive small molecules, long or rigid linker moieties are thought to be critical factors for efficient tagging of target protein.


Input: We previously reported the synthesis of a jasmonate glucoside probe with a highly rigid linker consisting of a triazoyl-phenyl (TAzP) moiety, and this probe demonstrated effective target tagging.

jasmonate glucoside

triazoyl-phenyl

TAzP


Input: Here we compare the TAzP probe with other rigid or flexible probes with respect to target tagging efficiency, hydrophobic parameters, aqueous solubility, and dihedral angles around the biaryl linkage by a combination of empirical and calculation methods.

TAzP

biaryl


Input: The rigid biaryl linkage of the TAzP probe has a skewed conformation that influences its aqueous solubility.

biaryl

TAzP


Input: Such features that include rigidness and good aqueous solubility resulted in highly efficient target tagging.


Input: These findings provide a promising guideline toward designing of better linkers for improving molecular probe performance.


Input: Discovery of a selective M 4 positive allosteric modulator based on the 3-amino-thieno [2, 3-b] pyridine-2-carboxamide scaffold: development of ML253, a potent and brain penetrant compound that is active in a preclinical model of schizophrenia.

3-amino-thieno [2, 3-b] pyridine-2-carboxamide


Input: Herein we report a next generation muscarinic receptor 4 (M (4)) positive allosteric modulator (PAM), ML253 which exhibits nanomolar activity at both the human (EC (50) = 56 nM) and rat (EC (50) = 176 nM) receptors and excellent efficacy by the left-ward shift of the ACh concentration response curve (fold shift, human = 106; rat = 50).

ACh


Input: In addition, ML253 is selective against the four other muscarinic subtypes, displays excellent CNS exposure and is active in an amphetamine-induced hyperlocomotion assay.

amphetamine


Input: Protein tyrosine phosphatase 1B inhibitory effect by dammarane-type triterpenes from hydrolyzate of total Gynostemma pentaphyllum saponins.

tyrosine

dammarane

triterpenes

saponins


Input: Protein tyrosine phosphatase 1B (PTP1B) is an important factor in non-insulin-dependent diabetes mellitus (type-2 diabetes), and a promising target for treatment of diabetes and obesity.

tyrosine


Input: Therefore, the aim of this study is to investigate the inhibitory activities of constituents (three new together with twelve known triterpenes compounds) isolated from the hydrolyzate of total saponins from Gynostemma pentaphyllum.

triterpenes

saponins


Input: Their structures were accomplished mainly base on the spectroscopic methods, and then were further confirmed by X-ray crystal diffraction.


Input: All the compounds were evaluated for inhibitory activity against PTP1B.


Input: Current data suggested that the compounds 1, 3, 12, 13 and 14 were considered to be potential as antidiabetic agents, in which they could significantly inhibit the PTP1B enzyme activity in a dose-dependent manner.


Input: Constant light disrupts the circadian rhythm of steroidogenic proteins in the rat adrenal gland.


Input: The circadian rhythm of corticosterone (CORT) secretion from the adrenal cortex is regulated by the suprachiasmatic nucleus (SCN), which is entrained to the light-dark cycle.

corticosterone

CORT


Input: Since the circadian CORT rhythm is associated with circadian expression of the steroidogenic acute regulatory (StAR) protein, we investigated the 24h pattern of hormonal secretion (ACTH and CORT), steroidogenic gene expression (StAR, SF-1, DAX1 and Nurr77) and the expression of genes involved in ACTH signalling (MC2R and MRAP) in rats entrained to a normal light-dark cycle.

CORT

CORT


Input: We found that circadian changes in ACTH and CORT were associated with the circadian expression of all gene targets; with SF-1, Nurr77 and MRAP peaking in the evening, and DAX1 and MC2R peaking in the morning.

CORT


Input: Since disruption of normal SCN activity by exposure to constant light abolishes the circadian rhythm of CORT in the rat, we also investigated whether the AM-PM variation of our target genes was also disrupted in rats exposed to constant light conditions for 5weeks.

CORT


Input: We found that the disruption of the AM-PM variation of ACTH and CORT secretion in rats exposed to constant light was accompanied by a loss of AM-PM variation in StAR, SF-1 and DAX1, and a reversed AM-PM variation in Nurr77, MC2R and MRAP.

CORT


Input: Our data suggest that circadian expression of StAR is regulated by the circadian expression of nuclear receptors and proteins involved in both ACTH signalling and StAR transcription.


Input: We propose that ACTH regulates the secretion of CORT via the circadian control of steroidogenic gene pathways that become dysregulated under the influence of constant light.

CORT


Input: Synthesis and anti-tumor evaluation of novel 25-hydroxyprotopanaxadiol analogs incorporating natural amino acids.

amino acids


Input: In the current study, derivatives of 25-hydroxyprotopanaxadiol (25-OH-PPD) were prepared and their in vitro anti-tumor activities were tested on six different human tumor cell lines by standard MTT assay.

MTT


Input: The results showed that combining an ester group combined with the presence of an amino acid moiety led to a 10-fold improved anti-tumor activity.

ester

amino acid


Input: Compound 1c exhibited the best anti-tumor activity in the in vitro assays.


Input: Compounds 2c, 3c, 4c, 5c, 6c and 8b showed better anti-tumor activities compared to the parent compound 25-OH-PPD.


Input: The current results may provide useful data for researching and developing new anti-cancer agents.


Input: Pulmonary delivery of an aerosolized recombinant human butyrylcholinesterase pretreatment protects against aerosolized paraoxon in macaques.

paraoxon


Input: Butyrylcholinesterase (BChE) is the leading pretreatment candidate against exposure to organophosphates (OPs), which pose an ever increasing public and military health.

organophosphates


Input: Since respiratory failure is the primary cause of death following acute OP poisoning, an inhaled BChE therapeutic could prove highly efficacious in preventing acute toxicity as well as the associated delayed neuropathy.


Input: To address this, studies have been performed in mice and macaques using Chinese Hamster Ovary cells (CHO)-derived recombinant (r) BChE delivered by the pulmonary route, to examine whether the deposition of both macaque (Ma) and human (Hu) rBChE administered as aerosols (aer) favored the creation and retention of an efficient protective " pulmonary bioshield " that could scavenge incoming (inhaled) OPs in situ thereby preventing entry into the circulation and inhibition of plasma BChE and AChE on red blood cells (RBC-AChE) and in cholinergic synapses.


Input: In contrast to parenteral delivery of rBChE, which currently requires posttranslational modification for good plasma stability, an unmodified aer-rBChE pretreatment given 1-40h prior to > 1 LD50 of aer-paraoxon (Px) was able to prevent inhibition of circulating cholinesterase in a dose-dependent manner.

paraoxon


Input: These studies are the first to show protection by rBChE against a pesticide such as paraoxon when delivered directly into the lung and bode well for the use of a non-invasive and consumer friendly method of rHuBChE delivery as a human treatment to counteract OP toxicity.

paraoxon


Input: Aspidin PB, a phloroglucinol derivative, induces apoptosis in human hepatocarcinoma HepG2 cells by modulating PI3K/Akt/GSK3 beta pathway.

Aspidin PB

phloroglucinol


Input: Aspidin PB, a phloroglucinol derivative isolated from Dryopteris fragrans (L.) Schott, has been previously reported to exert high biological activities.

Aspidin PB

phloroglucinol


Input: In the present study, we analyzed the apoptotic mechanisms of aspidin PB on human hepatoma cell line, HepG2.

aspidin PB


Input: Initially, aspidin PB was shown to inhibit the growth of HepG2 cells in a time and dose-dependent manner.

aspidin PB


Input: After treatment with aspidin PB for 72 h, 48 h and 24 h using MTT assay, the IC (50) values were 10. 59 mu M, 20. 86 mu M and 46. 59 mu M, respectively.

aspidin PB

MTT


Input: Aspidin PB was capable to induce apoptosis, as measured by mitochondrial membrane potential (Delta Psi m), acridine orange (AO) staining and propidium iodide (PI)/annexin V-FITC double staining.

Aspidin PB

acridine orange

propidium iodide

FITC


Input: To further explore the signaling pathway of aspidin PB-mediated apoptosis, we examined PI3K/Akt related proteins.

aspidin PB


Input: Western blot analysis revealed that aspidin PB inhibited PI3K expression, phosphorylation of Ser473 Akt and Ser9 GSK3 beta followed by up-regulation of nonsteroidal anti-inflammatory drugs activated gene-1 (NAG-1) expression.

aspidin PB


Input: Similarly, the effects of aspidin PB on PI3K, Akt, GSK3 beta, NAG-1 expression were abolished by treatment with the PI3K inhibitor, wortmannin.

aspidin PB

wortmannin


Input: Taken together, our data suggested that the PI3K/Akt/GSK3 beta signal pathway may represent one of the major mechanisms of the effects of aspidin PB on human hepatocarcinoma cells.

aspidin PB


Input: Adaptation of bifidobacteria to the gastrointestinal tract and functional consequences.


Input: Members of the genus Bifidobacterium are considered to be important constituents of the microbiota of animals, from insects to mammals.


Input: They are gut commensals extensively used by the food industry as probiotic microorganisms, since some strains have been shown to have specific beneficial effects.


Input: However, the molecular processes underlying their functional capacities to promote a healthy status in the host, as well as those involved in survival, colonization and persistence of bifidobacteria in the gut, are far from being completely understood.


Input: This review summarizes the current knowledge on the mechanisms used by bifidobacteria to cope with gastrointestinal factors and to adapt to them, and discusses the advantages of the adaptive traits acquired by these microorganisms as a consequence of their interactions with the gastrointestinal tract environment, as well as the impact of such adaptations in the functional characteristics of bifidobacteria.


Input: Inhibition of CIP2A determines erlotinib-induced apoptosis in hepatocellular carcinoma.

erlotinib


Input: Erlotinib is a small-molecular inhibitor of epidermal growth factor receptor (EGFR).

Erlotinib


Input: Here, we identify that cancerous inhibitor of protein phosphatase 2A (CIP2A) is a major determinant mediating erlotinib-induced apoptosis in hepatocellular carcinoma (HCC).

erlotinib


Input: Erlotinib showed differential effects on apoptosis in 4 human HCC cell lines.

Erlotinib


Input: Erlotinib induced significant apoptosis in Hep3B and PLC5 cell lines; however, Huh-7 and HA59T cell lines showed resistance to erlotinib-induced apoptosis at all tested doses.

Erlotinib

erlotinib


Input: Down-regulation of CIP2A, a cellular inhibitor of protein phosphatase 2A (PP2A), mediated the apoptotic effect of erlotinib in HCC.

erlotinib


Input: Erlotinib inhibited CIP2A in a dose-and time-dependent manner in all sensitive HCC cells whereas no alterations in CIP2A were found in resistant cells.

Erlotinib


Input: Overexpression of CIP2A upregulated phospho-Akt and protected Hep3B cells from erlotinib-induced apoptosis.

phospho

erlotinib


Input: In addition, silencing CIP2A by siRNA restored the effects of erlotinib in Huh-7 cells.

erlotinib


Input: Moreover, adding okadaic acid, a PP2A inhibitor, abolished the effects of erlotinib on apoptosis in Hep3B cells; and forskolin, a PP2A agonist enhanced the effect of erlotinib in resistant HA59T cells.

okadaic acid

erlotinib

forskolin

erlotinib


Input: Combining Akt inhibitor MK-2206 with erlotinib restored the sensitivity of HA59T cells to erlotinib.

erlotinib

erlotinib


Input: Furthermore, in vivo xenograft data showed that erlotinib inhibited the growth of PLC5 tumor but had no effect on Huh-7 tumor.

erlotinib


Input: Erlotinib downregulated CIP2A and upregulated PP2A activity in PLC5 tumors, but not in Huh-7 tumors.

Erlotinib


Input: In conclusion, inhibition of CIP2A determines the effects of erlotinib on apoptosis in HCC.

erlotinib


Input: CIP2A may be useful as a therapeutic biomarker for predicting clinical response to erlotinib in HCC treatment.

erlotinib


Input: Boldine protects endothelial function in hyperglycemia-induced oxidative stress through an antioxidant mechanism.

Boldine


Input: Increased oxidative stress is involved in the pathogenesis and progression of diabetes.


Input: Antioxidants are therapeutically beneficial for oxidative stress-associated diseases.


Input: Boldine ([s]-2, 9-dihydroxy-1, 10-dimethoxyaporphine) is a major alkaloid present in the leaves and bark of the boldo tree (Peumus boldus Molina), with known an antioxidant activity.

Boldine

[s]-2, 9-dihydroxy-1, 10-dimethoxyaporphine


Input: This study examined the protective effects of boldine against high glucose-induced oxidative stress in rat aortic endothelial cells (RAEC) and its mechanisms of vasoprotection related to diabetic endothelial dysfunction.

boldine

glucose


Input: In RAEC exposed to high glucose (30 mM) for 48 h, pre-treatment with boldine reduced the elevated ROS and nitrotyrosine formation, and preserved nitric oxide (NO) production.

glucose

boldine

nitrotyrosine

nitric oxide

NO


Input: Pre-incubation with beta-NAPDH reduced the acetylcholine-induced endothelium-dependent relaxation; this attenuation was reversed by boldine.

beta-NAPDH

acetylcholine

boldine


Input: Compared with control, endothelium-dependent relaxation in the aortas of streptozotocin (STZ)-treated diabetic rats was significantly improved by both acute (1 mu M, 30 min) and chronic (20mg/kg/daily, i. p., 7 days) treatment with boldine.

streptozotocin

STZ

boldine


Input: Intracellular superoxide and peroxynitrite formation measured by DHE fluorescence or chemiluminescence assay were higher in sections of aortic rings from diabetic rats compared with control.

superoxide

peroxynitrite

DHE


Input: Chronic boldine treatment normalized ROS over-production in the diabetic group and this correlated with reduction of NAD (P) H oxidase subunits, NOX2 and p47 (phox).

boldine

NAD (P) H


Input: The present study shows that boldine reversed the increased ROS formation in high glucose-treated endothelial cells and restored endothelial function in STZ-induced diabetes by inhibiting oxidative stress and thus increasing NO bioavailability.

boldine

glucose

STZ

NO


Input: Relationship between DNA damage in sperm after ex vivo exposure and abnormal embryo development in the progeny of the three-spined stickleback.


Input: Many xenobiotics released in the aquatic environment exhibit a genotoxic potential toward organisms.


Input: Long term exposure to such compounds is expected to lead to multigenerational reproductive defects, further influencing the recruitment rate and hence, the population dynamics.


Input: Paternal exposure to genotoxicants was previously shown to increase abnormal development in the progeny of mammalian or aquatic species.


Input: The aim of this study was to evaluate the relationship between DNA damage in sperm of the fish three-spined stickleback and progeny developmental defects.


Input: Spermatozoa were exposed ex vivo to an alkylating agent (methyl methanesulfonate) before in vitro fertilization and DNA damage was assessed by the alkaline comet assay.

methyl methanesulfonate


Input: A significant relationship between abnormal development and sperm DNA damage was underlined.


Input: This study illustrates the interest to use germ cell DNA damage after ex vivo exposure to evaluate the impact of genotoxic compounds on progeny fitness in aquatic organisms.


Input: Integrated pharmacokinetic-driven approach to screen candidate anticancer drugs for brain tumor chemotherapy.


Input: The goal of the study was to develop an effective screening strategy to select new agents for brain tumor chemotherapy from a series of low molecular weight anticancer agents [ON123x] by the combined use of in silico, in vitro cytotoxicity, and in vitro ADME profiling studies.


Input: The results of these studies were cast into a pipeline of tier 1 and tier 2 procedures that resulted in the identification of ON123300 as the lead compound.


Input: Of the 154 ON123xx compounds, 13 met tier 1 screening criteria based on physicochemical properties [i. e., MW < 450 Da, predicted log P between 2 and 3. 5] and in vitro glioma cell cytotoxicity [i. e., IC50 < 10 mu M] and were further tested in tier 2 assays.


Input: The tier 2 profiling studies consisted of metabolic stability, MDCK-MDR1 cell permeability and plasma and brain protein binding that were combined to globally assess whether favorable pharmacokinetic properties and brain penetration could be achieved in vivo.


Input: In vivo cassette dosing studies were conducted in mice for 12 compounds that permitted examination of in vitro/in vivo relationships that confirmed the suitability of the in vitro assays.


Input: A parameter derived from the in vitro assays accurately predicted the extent of drug accumulation in the brain based on the area under the drug concentration-time curve in brain measured in the cassette dosing study (r (2) = 0. 920).


Input: Overall, the current studies demonstrated the value of an integrated pharmacokinetic-driven approach to identify potentially efficacious agents for brain tumor chemotherapy.


Input: Two new C-benzylated dihydrochalcone derivatives from the leaves of Melodorum siamensis.

C-benzylated dihydrochalcone


Input: Two new C-benzylated dihydrochalcone derivatives, 4, 2', 4'-trihydroxy-6'-methoxy-3' (2''-hydroxybenzyl) dihydrochalcone (1) and 2', 4'-dihydroxy-4, 6'-dimethoxy-3' (2''-hydroxybenzyl) dihydrochalcone (2), along with six known flavonoid derivatives (3-8), a known dihydrochalcone dimer (9), three known aromatic esters (10-12), and one known aromatic amide (13), were isolated from the leaves of Melodorum siamensis.

C-benzylated dihydrochalcone

4, 2', 4'-trihydroxy-6'-methoxy-3' (2''-hydroxybenzyl) dihydrochalcone

2', 4'-dihydroxy-4, 6'-dimethoxy-3' (2''-hydroxybenzyl) dihydrochalcone

flavonoid

dihydrochalcone

aromatic esters

aromatic amide


Input: The structures of the compounds were elucidated by spectroscopic analysis, mainly 1D and 2D NMR techniques (1H, 13C, COSY, HMQC, and HMBC), as well as by comparison with literature data.


Input: The isolated compounds with a sufficient amount for biological assays were evaluated for their antimalarial, antimycobactirial, and cytotoxic activities.


Input: Compounds 1, 2, and 13 exhibited strong cytotoxicity against human tumor cell lines KB and NCI-H187, with IC50 values in the range of 0. 66-7. 16 micro g/mL.


Input: Avoidance of contaminated sediments by an amphipod (Melita plumulosa), A harpacticoid copepod (Nitocra spinipes), and a snail (Phallomedusa solida).


Input: The distribution of contaminants is seldom homogeneous in aquatic systems.


Input: In the present study, the avoidance response of Melita plumulosa, Nitocra spinipes, and Phallomedusa solida when exposed to contaminated sediments was investigated.


Input: Test vessels were designed to allow the congruent placement of two sediments and assessment of the movement of organisms between the sediments.


Input: When exposed to reference sediment, each species dispersed evenly between test chambers regardless of differences in sediment particle size.


Input: In the presence of contaminated sediment, the magnitude and rate of avoidance varied.


Input: Avoidance assays showed that test species avoided contaminated sediment as early as 6, 6, and 24 h following exposure for N. spinipes, P. solida, and M. plumulosa, respectively.


Input: The 48-h avoidance response of M. plumulosa for nine contaminated sediments of varying toxicity showed that avoidance was generally greater for sediments which elicited greater 10-d lethality to this species.


Input: The study demonstrated that each of these species has the ability to respond to chemical cues in the environment to inhabit sediment that provides the best opportunity for survival.


Input: The avoidance response for each species indicates the potential for developing rapid screening methods to assess sediment quality.


Input: Evidence suggests that avoidance was related to sediment toxicity and that static 10-d toxicity methods are likely to overestimate toxicity for species, which would avoid contamination in heterogeneous field settings.


Input: Facile and clean release of vertical Si nanowires by wet chemical etching based on alkali hydroxides.

Si

alkali hydroxides


Input: A simple method to release Si nanowires (SiNWs) from a substrate, with their original length almost intact, is demonstrated.

Si


Input: By exploiting the unique chemistry involved for the fabrication of vertical arrays of SiNWs in metal-assisted chemical etching (MaCE) based either on HF/AgNO3 or HF/H2O2 chemistries, wet etching with alkali hydroxides such as NaOH or KOH preferentially attacks the bottom part of the vertical SiNWs.

HF

HF

alkali hydroxides

NaOH

KOH


Input: A protective layer of Si oxide is found to exist on the outer wall of the SiNWs and to play the key role of etch mask during the release-etching by alkali hydroxides.

Si oxide

alkali hydroxides


Input: The clean release of SiNWs also enables the repeated use of the Si substrate for the fabrication of vertical SiNW arrays by MaCE.

SiNWs


Input: The released SiNWs are further used for the fabrication of field-effect transistors on a flexible plastic substrate.


Input: The method developed here, when combined with a suitable assembling technique, can be very useful in implementing flexible electronics, or in the fabrication of SiNW composites with other functional materials.


Input: Enantioseparation of four organophosphonate derivatives on N-(3, 5-dinitrobenzoyl)-L-leucine-n-propylamide stationary phase by molecular modeling.

organophosphonate

N-(3, 5-dinitrobenzoyl)-L-leucine-n-propylamide


Input: Four groups of organophosphonate derivatives enantiomers were separated on N-(3, 5-dinitrobenzoyl)-S-leucine chiral stationary phase.

organophosphonate

N-(3, 5-dinitrobenzoyl)-S-leucine


Input: The three-dimensional structures of the complexes between the single enantiotopic chiral compounds and chiral stationary phase have been studied using molecular model and molecular dynamics simulation.


Input: Detailed results regarding the conformation, auto-docking, and thermodynamic estimation are presented.


Input: The elution order of the enantiomer could be determined from the energy.


Input: The predicted chiral discrimination was obtained by computational results.


Input: Lattice deformation and domain distortion in the self-assembly of block copolymer thin films on chemical patterns.


Input: The self-assembly of cylinder-forming block copolymer (BCP) microdomains confined within chemical stripe patterns of widths incommensurate with the natural period of the copolymers, L0, is studied.


Input: It is shown that this incommensurability causes changes in both the shapes of the microdomains and their spatial period.


Input: Specifically, a transition from n to n + 1 rows of microdomains is observed when the stripe width is about n +/- 1/2 L0.


Input: When the stripe' s width is comparable to L0, ellipticity of microdomains can be induced with an aspect ratio up to 2. 2.


Input: Free energy models are applied to describe the energetic origin of such behavior.


Input: Although our observations qualitatively resemble results in sphere-forming BCPs confined in topographical trenches, the quantitative difference is noteworthy and technologically important for the design of nanostructures with programmable shapes.


Input: Enantioanalysis of pipecolic acid with stochastic and potentiometric microsensors.

pipecolic acid


Input: Stochastic and potentiometric microsensors based on porphyrins and polymeric surfactants such as polysodium N-undecanoyl-L-leucylvanilate and polysodium N-undecanoyl-L-vanilate were developed for enantioselective assay of pipecolic acid.

porphyrins

polysodium N-undecanoyl-L-leucylvanilate

polysodium N-undecanoyl-L-vanilate

pipecolic acid


Input: The matrices used for the design of the stochastic sensors were diamond paste and graphite paste, while the matrix used for the design of potentiometric sensors was carbon paste.

diamond

graphite

carbon


Input: The response characteristics of the microsensors were determined for the enantiomers of pipecolic acid.

pipecolic acid


Input: The response characteristics, selectivity, and enantioselectivity studies proved that the proposed microsensors can be used for clinical enantioanalysis of pipecolic acid in biological fluids, e. g., urine and whole blood.

pipecolic acid


Input: Brewster angle microscopy of Langmuir films of athabasca bitumens, n-C5 asphaltenes, and SAGD bitumen during pressure-area hysteresis.


Input: Bitumen films formed on water surfaces have negative consequences, both environmental and economic.


Input: CanmetENERGY has placed considerable research emphasis on understanding the structures of the bitumen films on water as a necessary step before optimization of bitumen extraction.


Input: The detailed structures of the adsorbed molecules and, especially, the role of asphaltene molecules at the interfaces are still under scrutiny and debate.


Input: In the present study, we compared bitumen and asphaltene films as they were compressed and expanded under various surface pressures in order to achieve a clearer understanding of bitumen film structures.


Input: We used a customized NIMA Langmuir trough interfaced to a Brewster angle microscope (BAM) and CCD camera (Nanofilm _ ep3BAM, Accurion, previously Nanofilm Gmbh) to study images of bitumen films at the air/water interface.


Input: The bitumen film appeared uniform with high reflectivity at a surface pressure of 18 mN. m (-1) and exhibited a coarse pebblelike interface with reduced reflectivity in the liquid condensed (LC) phase at higher pressures (18-35 mN. m (-1)).


Input: During the first cycle of compression asphaltene films showed well-defined phase transitions and a uniformly smooth interface in the LC phase between 9 and 35 mN. m (-1).


Input: However, folding or buckling occurred at surface pressures from 35 to 44 mN. m (-1).


Input: On expansion, asphaltene films appeared to break into islands.


Input: The hysteresis of the pressure-area isotherm was much larger for asphaltenes than for bitumen.


Input: In both compression and expansion cycles, BAM images for bitumen films appeared to be more reproducible than those of the asphaltene films at the same surface pressures.


Input: Films for low-degrees API SAGD bitumen were almost identical to those for surface-mined bitumen.


Input: Films formed from partially deasphalted surface-mined bitumens showed higher compressibility and lower rigidity than the original bitumen.


Input: The BAM images illustrated significant differences between the partially deasphalted and original bitumen films.


Input: Other components in bitumen also played important roles in determining the interfacial properties of bitumen films.


Input: Novel 2-aminooctahydrocyclopentalene-3a-carboxamides as potent CCR2 antagonists.

2-aminooctahydrocyclopentalene-3a-carboxamides


Input: Novel CCR2 antagonists with a novel 2-aminooctahydrocyclopentalene-3a-carboxamide scaffold were designed.

2-aminooctahydrocyclopentalene-3a-carboxamide


Input: SAR studies led to a series of potent compounds.


Input: For example, compound 51 had a good PK profile in both dog and monkey, and exhibited excellent efficacy when dosed orally in an inflammation model in hCCR2 KI mice.


Input: In addition, an asymmetric synthesis to the core structures was developed.


Input: Assessing the chemical accuracy of protein structures via peptide acidity.


Input: Although the protein native state is a Boltzmann conformational ensemble, practical applications often require a representative model from the most populated region of that distribution.


Input: The acidity of the backbone amides, as reflected in hydrogen exchange rates, is exquisitely sensitive to the surrounding charge and dielectric volume distribution.

amides

hydrogen


Input: For each of four proteins, three independently determined X-ray structures of differing crystallographic resolution were used to predict exchange for the static solvent-exposed amide hydrogens.

amide hydrogens


Input: The average correlation coefficients range from 0. 74 for ubiquitin to 0. 93 for Pyrococcus furiosus rubredoxin, reflecting the larger range of experimental exchange rates exhibited by the latter protein.


Input: The exchange prediction errors modestly correlate with the crystallographic resolution.


Input: MODELLER 9v6-derived homology models at ~ 60% sequence identity (36% identity for chymotrypsin inhibitor CI2) yielded correlation coefficients that are ~ 0. 1 smaller than for the cognate X-ray structures.


Input: The most recently deposited NOE-based ubiquitin structure and the original NMR structure of CI2 fail to provide statistically significant predictions of hydrogen exchange.

hydrogen


Input: However, the more recent RECOORD refinement study of CI2 yielded predictions comparable to the X-ray and homology model-based analyses.


Input: Incidence and predictors of right paraesophageal lymph node metastasis of N0 papillary thyroid carcinoma located in the right lobe.


Input: Papillary thyroid carcinoma (PTC) frequently metastasizes to the regional lymph nodes and, thus, guidelines edited by Japan Association of Endocrine Surgeons/Japanese Society of Thyroid Surgery routinely recommend central node dissection even for patients with no clinically detectable node metastasis (N0).


Input: However, in the central compartment, metastasis to the right paraesophageal node has not been intensively investigated.


Input: We investigated the incidence and predictors of right paraesophageal node metastasis based on pre-and intraoperative findings in 922 patients with N0 PTC in the right lobe.


Input: Fourteen percent of patients were microscopically positive for right paraesophageal node metastasis, and the incidence was smaller than that for pre-and right paratracheal node metastasis (46%).


Input: On multivariate analysis, a tumor size >= 2 cm and significant extrathyroid extension were independent predictors of metastasis.


Input: Microscopically pre-and right paratracheal node-positive PTC more often (p < 0. 0001) metastasized to the right paraesophageal node.


Input: Taken together, in N0 PTC in the right lobe, right paraesophageal node dissection should be considered in tumors 2 cm or larger and/or with significant extrathyroid extension, or when pre-and right paratracheal node metastasis is suspected based on the intraoperative findings.


Input: Effects of ozone and fine particulate matter (PM (2. 5)) on rat system inflammation and cardiac function.

ozone


Input: In order to understand the toxic mechanisms of cardiovascular system injuries induced by ambient PM (2. 5) and/or ozone, a subacute toxicological animal experiment was designed with exposure twice a week for 3 continuous weeks.

ozone


Input: Wistar rats were randomly categorized into 8 groups (n = 6): 1 control group, 3 groups exposed to fine particulate matters (PM (2. 5)) alone at 3 doses (0. 2, 0. 8, or 3. 2 mg/rat), 1 group to ozone (0. 81 ppm) alone and 3 groups to ozone plus PM (2. 5) at 3 doses (0. 2, 0. 8, or 3. 2 mg/rat).

ozone

ozone


Input: Heart rate (HR) and electrocardiogram (ECG) was monitored at approximately 24-h both after the 3rd exposure and the last (6th) exposure, and systolic blood pressure (SBP) was monitored at approximately 24-h after the 6th exposure.


Input: Biomarkers of systemic inflammation and injuries (CRP, IL-6, LDH, CK), heart oxidative stress (MDA, SOD) and endothelial function (ET-1, VEGF) were analyzed after the 6th exposure.

MDA


Input: Additionally, myocardial ultrastructural alterations were observed under transmission electron microscopy (TEM) for histopathological analyses.


Input: Results showed that PM (2. 5) alone exposure could trigger the significant increase of CRP, MDA, CK, ET-1 and SBP and decrease of heart rate variability (HRV), a marker of cardiac autonomic nervous system (ANS) function.

MDA


Input: Ozone alone exposure in rats did not show significant alterations in any indicators.

Ozone


Input: Ozone plus PM (2. 5) exposure, however, induced CRP, IL-6, CK, LDH and MDA increase, SOD and HRV decrease significantly in a dose-response way.

Ozone

MDA


Input: Meanwhile, abnormal ECG types were monitored in rats exposed to PM (2. 5) with and without ozone and obvious myocardial ultrastructural changes were observed by TEM.

ozone


Input: In conclusion, PM (2. 5) alone exposure could cause inflammation, endothelial function and ANS injuries, and ozone potentiated these effects induced by PM (2. 5).

ozone


Input: Dynamics of silver nanoparticle formation and agglomeration inside the cavitation bubble after pulsed laser ablation in liquid.

silver


Input: The formation of nanoparticles within the laser-induced cavitation bubble is studied in situ using small angle X-ray scattering with high spatiotemporal resolution.


Input: Directly after laser ablation, two different particle fractions consisting of compact primary particles of 8-10 nm size and agglomerates of 40-60 nm size are formed.


Input: The abundance of these species is strongly influenced by the dynamics of the oscillating cavitation bubble.


Input: Primary particle mass is most abundant during maximal expansion of the first bubble and reappears a little weaker in the rebound.


Input: In contrast to this, the mass abundance of agglomerates is relatively low in the first bubble but strongly increases during first bubble collapse and following rebound.


Input: Although most of the ablated material is trapped inside the bubble and follows its oscillation, a minor fraction of both species could be detected outside the cavitation bubble even before its final collapse.


Input: Limits of metastability in amorphous ices: 2H-NMR relaxation.


Input: The high-frequency reorientation dynamics of O-(2) H bonds is investigated in various amorphous ices including eHDA (expanded high density amorphous ice), LDA-II (low density amorphous ice II) and HGW (hyperquenched glassy water) using (2) H-NMR spin-lattice relaxation as a local probe.

O-(2) H

(2) H


Input: Both low density forms, HGW and LDA-II, show similar spin-lattice relaxation but differ in the thermal stability with respect to the transition into crystalline cubic ice I (c).


Input: HGW already transforms slightly above 135 K whereas LDA-II crystallizes at 150 K.


Input: eHDA is distinguishable from other high density amorphous ices in its thermal stability and spin-lattice relaxation.


Input: Its relaxation times are much larger compared to those of VHDA (very high density amorphous ice) and uHDA (unrelaxed high density amorphous ice).


Input: eHDA does not show annealing effects, transforms sharply into LDA-II above 123 K and provides higher thermal stability as compared to other high density forms.


Input: Nanoporous silicon networks as anodes for lithium ion batteries.

silicon

lithium


Input: Nanoporous silicon (Si) networks with controllable porosity and thickness are fabricated by a simple and scalable electrochemical process, and then released from Si wafers and transferred to flexible and conductive substrates.

silicon

Si

Si


Input: These nanoporous Si networks serve as high performance Li-ion battery electrodes, with an initial discharge capacity of 2570 mA h g (-1), above 1000 mA h g (-1) after 200 cycles without any electrolyte additives.

Si

Li


Input: Recent progress in the development and use of organic ionic plastic crystal electrolytes.


Input: Significant progress has been made recently in the development of Organic Ionic Plastic Crystals (OIPCs), a unique family of solid state electrolytes with applications in electrochemical devices such as lithium batteries and dye-sensitised solar cells.

lithium


Input: The negligible volatility of OIPCs renders them more suitable than molecular species for long-term device use, while the high thermal and electrochemical stability of many OIPCs fulfils an essential requirement for solid state electrolytes for many device applications.


Input: However, the complex mechanisms of conduction through these materials, both in their pure state and in the presence of a small amount of a second component (such as lithium salts to enable their use in lithium batteries) are still not fully understood.

lithium

lithium


Input: At the same time, the range of anions and cations utilised in the synthesis of plastic crystal phases continues to increase.


Input: This perspective concentrates on recent research into both fundamental and device-oriented aspects of these materials.


Input: Important fundamental understanding of the physical properties and transport mechanisms of different OIPCs has been achieved through use of techniques including variable temperature solid-state NMR and crystallographic analysis, as well as detailed molecular dynamics simulations.


Input: In parallel, the applicability of these materials as electrolytes for dye-sensitised solar cells and lithium batteries is being more widely demonstrated.

lithium


Input: The possibility of using OIPCs as solid state electrolytes for fuel cells is also discussed.


Input: Deep brain stimulation of the subthalamic nucleus, but not dopaminergic medication, improves proactive inhibitory control of movement initiation in Parkinson' s disease.


Input: Slowness in movement initiation is a cardinal feature of Parkinson' s disease (PD) that is still poorly understood and unsuccessfully alleviated by standard therapies.


Input: Here, we raise this major clinical issue within the framework of a novel theoretical model that allows a better understanding of the basic mechanisms involved in movement initiation.


Input: This model assumes that movement triggering is inhibited by default to prevent automatic responses to unpredictable events.


Input: We investigated to which extent the top-down control necessary to release this locking state before initiating actions is impaired in PD and restored by standard therapies.


Input: We used a cue-target reaction time task to test both the ability to initiate fast responses to targets and the ability to refrain from reacting to cues.


Input: Fourteen patients with dopaminergic (DA) medication and 11 with subthalamic nucleus (STN) stimulation were tested on and off treatment, and compared with 14 healthy controls.


Input: We found evidence that patients withdrawn from treatment have trouble voluntarily releasing proactive inhibitory control; while DA medication broadly reduces movement initiation latency, it does not reinstate a normal pattern of movement initiation; and stimulation of the STN specifically re-establishes the efficiency of the top-down control of proactive inhibition.


Input: These results suggest that movement initiation disorders that resist DA medication are due to executive, not motor, dysfunctions.


Input: This conclusion is discussed with regard to the role the STN may play as an interface between non-DA executive and DA motor systems in cortico-basal ganglia loops.


Input: High physical fitness in young adulthood reduces the risk of fractures later in life in men: A nationwide cohort study.


Input: A few studies have indicated that self-reported physical activity is associated with the risk of fractures in middle-aged and elderly men.


Input: We investigated whether objectively measured physical fitness in young adulthood was associated with the risk of low-energy fractures later in life in men.


Input: Aerobic capacity and isometric muscle strength were measured in 435, 445 Swedish men who were conscripted for military service from 1969 to 1978.


Input: Incident fractures were searched in national registers.


Input: During a median follow-up period of 35 years (range, 11-41 years), 8030 subjects sustained at least one fracture, increasing the risk of death 1. 8 times (95% CI, 1. 6-2. 0) during follow up.


Input: When comparing men in the lowest and highest decile of physical fitness, the risk of a fracture was 1. 8 times higher (95% CI, 1. 6-2. 1) and that of hip fracture was 2. 7 times higher (95% CI, 1. 6-4. 7).


Input: The risk of fracture was also 1. 4 to 1. 5 times higher when comparing the extreme deciles of muscle strength (p < 0. 001 for all).


Input: In a subcohort of 1009 twin pairs, up to 22% of the variation in physical fitness and 27% to 39% of the variation in muscle strength was attributable to environmental factors unique to one twin; eg, physical activity.


Input: In conclusion, low aerobic capacity and muscle strength in young adulthood are associated with an increased risk of low-energy fractures later in life.


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


Input: Ion pair dynamics: solvolyses of chiral 1, 3-diarylallyl carboxylates as a case study.

chiral 1, 3-diarylallyl carboxylates


Input: Chiral ion pairs play a key role in modern enantioselective synthesis, though little is known about their properties.


Input: We have now used the special features of unsymmetrically substituted allyl derivatives to obtain unprecedented insight into ion pair dynamics.

allyl


Input: By employing chiral high-performance liquid chromatography, it was possible to follow the time-dependent concentrations of all four isomeric esters (two regioisomeric pairs of enantiomers) and all four isomeric alcohols generated during the hydrolysis of enantiopure 1-(4-chlorophenyl)-3-phenylallyl and 3-(4-chlorophenyl)-1-phenylallyl 4-nitrobenzoates.

esters

alcohols

1-(4-chlorophenyl)-3-phenylallyl and 3-(4-chlorophenyl)-1-phenylallyl 4-nitrobenzoates


Input: Combination of these results with the directly measured rate constant for the reaction of the laser-flash photolytically generated 1-(4-chlorophenyl)-3-phenylallyl cation with water provided a complete mechanistic scheme for allyl carboxylate solvolysis.

allyl carboxylate


Input: It is demonstrated that solvolysis and internal return can be explained by the same intermediates.


Input: The correlation equation log k = s (N) (N + E) was used to elucidate the variable importance of external and internal return in the solvolysis reactions.


Input: This information will be crucial for the interpretation of the ultrafast dynamics of ion pairs generated by femtosecond laser pulses.


Input: Effects of ultrasound frequency and acoustic amplitude on the size of sonochemically active bubbles-Theoretical study.


Input: Numerical simulation of chemical reactions inside an isolated spherical bubble of oxygen has been performed for various ambient bubble radii at different frequencies and acoustic amplitudes to study the effects of these two parameters on the range of ambient radius for an active bubble in sonochemical reactions.

oxygen


Input: The employed model combines the dynamic of bubble collapse with the chemical kinetics of single cavitation bubble.


Input: Results from this model were compared with some experimental results presented in the literature and good apparent trends between them were observed.


Input: The numerical calculations of this study showed that there always exists an optimal ambient bubble radius at which the production of oxidizing species at the end of the bubble collapse attained their upper limit.


Input: It was shown that the range of ambient radius for an active bubble increased with increasing acoustic amplitude and decreased with increasing ultrasound frequency.


Input: The optimal ambient radius decreased with increasing frequency.


Input: Analysis of curves showing optimal ambient radius versus acoustic amplitude for different ultrasonic frequencies indicated that for 200 and 300kHz, the optimal ambient radius increased linearly with increasing acoustic amplitude up to 3atm.


Input: However, slight minima of optimal radius were observed for the curves obtained at 500 and 1000kHz.


Input: Decolourization of direct blue 15 by Fenton/ultrasonic process using a zero-valent iron aggregate catalyst.

direct blue 15

zero-valent iron


Input: Decolourization of direct azo dye, direct blue 15 (DB15), by an advanced Fenton process coupled with ultrasonic irradiation (Fenton/US) was investigated.

azo

direct blue 15


Input: Zero-valent iron (ZVI) aggregates were used as the catalyst.

Zero-valent iron

ZVI


Input: A positive synergistic effect occurred when Fenton' s reagent was combined with ultrasonic irradiation.

Fenton' s reagent


Input: Experimental results showed that the optimum conditions for decolourization were pH 3. 0, Fe (0) 1g/L, H (2) O (2) 5. 15 x 10 (-3) mol/L with ultrasound density of 120W/L at 60kHz.

Fe (0)

H (2) O (2)


Input: These conditions yielded 99% decolouration of 4. 7 x 10 (-5) M DB15 (4130 ADMI) solution within 10min.


Input: DB15 decolouration follows the first-order decolouration kinetics.


Input: Although the solutions containing H (2) CO (3), Cl (-), ClO (4) (-), NO (3) (-) and SO (4) (2-) ions did not have a significant effect on the decolouration, the H (2) PO (4) (-) ion did decrease the decolouration rate.

H (2) CO (3)

Cl (-)

ClO (4) (-)

NO (3) (-)

SO (4) (2-)

H (2) PO (4) (-)


Input: High ultrasonic input power accelerated the reaction and increased decolourization efficiency.


Input: The cost effectiveness of this process at high ultrasound density could be controlled despite the high electricity costs incurred by the process.


Input: ZVI aggregates were reusable; however, an increase in the number of times ZVI was recycled decreased the decolourization rate.

ZVI

ZVI


Input: This study demonstrates that a Fenton/US process can effectively decolour the direct azo dye DB15 in wastewater.

azo


Input: Effects of bidentate coordination on the molecular properties rapta-C based complex using theoretical approach.

rapta-C


Input: In this work several quantum properties including the NEDA and QTAIM are computed on three models of rapta-C complexes using DFT with hybrid functional and basis set with ECP and without ECP.

rapta-C


Input: Several interesting correlations within the observed properties and also with the reported experimental behaviors of these complexes including their biological activities are presented.


Input: The study shows that the stability of the two complexes with bidentate ligands is associated with their high hydrogen bonding stability and existence of stronger non-covalent metal-ligand bonds.

hydrogen


Input: The energy decomposition analysis indicated that inter-atomic interactions in the three forms of rapta-C complexes and their stability are governed by the charge transfer term with significant contributions from polarization and electrostatic terms.

rapta-C


Input: The higher stability of complex 1 and 2 over 3 comes from the lower exchange repulsion and higher polarization contributions to their stability which agrees perfectly with the experimental observation.


Input: Our results provide insight into the nature of intramolecular forces that influence the structural stability of the three complexes.


Input: Genome-wide mapping of human DNA-replication origins: levels of transcription at ORC1 sites regulate origin selection and replication timing.


Input: We report the genome-wide mapping of ORC1 binding sites in mammals, by chromatin immunoprecipitation and parallel sequencing (ChIP-seq).


Input: ORC1 binding sites in HeLa cells were validated as active DNA replication origins (ORIs) using Repli-seq, a method that allows identification of ORI-containing regions by parallel sequencing of temporally ordered replicating DNA.


Input: ORC1 sites were universally associated with transcription start sites (TSSs) of coding or noncoding RNAs (ncRNAs).


Input: Transcription levels at the ORC1 sites directly correlated with replication timing, suggesting the existence of two classes of ORIs: those associated with moderate/high transcription levels (>= 1 RNA copy/cell), firing in early S and mapping to the TSSs of coding RNAs; and those associated with low transcription levels (< 1 RNA copy/cell), firing throughout the entire S and mapping to TSSs of ncRNAs.


Input: These findings are compatible with a scenario whereby TSS expression levels influence the efficiency of ORC1 recruitment at G (1) and the probability of firing during S.


Input: Highlights on contemporary recognition and sensing of fluoride anion in solution and in the solid state.

fluoride


Input: The fluoride anion has recently gained well deserved attention among the scientific community for its importance in many fields of human activities, but also for concerns on its effect on health and the environment.

fluoride


Input: Although surprisingly overlooked in systematic studies in the past, fluoride has nowadays become a topical target in the field of anion recognition.

fluoride


Input: A multitude of scientific reports are published every year where the establishment of efficient and specific interaction with fluoride is sought in polar and aqueous media.

fluoride


Input: Here, the emphasis is directed to a detailed description of the most interesting contemporary studies in the field, with a particular focus given to those published in the last few years.


Input: Phosphorylation of ribosomal protein S3 and antiapoptotic TRAF2 protein mediates radioresistance in non-small cell lung cancer cells.


Input: Radioresistance is considered as a main factor restricting efficacy of radiotherapy.


Input: However, the exact molecular mechanism of radioresistance has not been explained yet.


Input: In this study, to elucidate radioresistance mechanism in lung cancer, we compared radiation responses in two types of non-small cell lung cancer (NSCLC) cells with different radiosensitivity and identified key molecules conferring radioresistance.


Input: In radioresistant NSCLC cells, ionizing radiation (IR) led to casein kinase 2 alpha (CK2 alpha)-and PKC-mediated phosphorylation of rpS3 and TRAF2, respectively, which induced dissociation of rpS3-TRAF2 complex and NF-kappa B activation, resulting in significant up-regulation of prosurvival genes (cIAP1, cIAP2, and survivin).


Input: Also, dissociated phospho-rpS3 translocated into nucleus and bound with NF-kappa B complex (p65 and p50), contributing to p65 DNA binding property and specificity.

phospho


Input: However, in radiosensitive NSCLC cells, IR-mediated rpS3 phosphorylation was not detected due to the absence of CK2 alpha overexpression.


Input: Consequently, IR-induced rpS3-TRAF2 complex dissociation, NF-kappa B activation, and prosurvival gene expression were not presented.


Input: Taken together, our findings revealed a novel radioresistance mechanism through functional orchestration of rpS3, TRAF2, and NF-kappa B in NSCLC cells.


Input: Moreover, we provided the first evidence for the function of rpS3 as a new TRAF2-binding protein and demonstrated that phosphorylation of both rpS3 and TRAF2 is a key control point of radioresistance in NSCLC cells.


Input: These results suggest that regulation of rpS3 and TRAF2 in combination with radiotherapy could have high pharmacological therapeutic potency for radioresistance of NSCLC.


Input: Theoretical studies on muti-hydroxyimides as highly efficient catalysts for aerobic oxidation.

hydroxyimides


Input: N, N-dihydroxypyromellitimide (NDHPI) and N, N', N''-trihydroxyisocyanuric acid (THICA) have been recently demonstrated to act as better carbon-radical-producing catalysts than the popular N-hydroxyphthalimide (NHPI).

N, N-dihydroxypyromellitimide

NDHPI

N, N', N''-trihydroxyisocyanuric acid

THICA

carbon

N-hydroxyphthalimide

NHPI


Input: To gain a mature understanding of these particular catalysts, herein their geometrical, electronic, and thermochemical properties, as well as their catalytic activities, have been systemically investigated by a theoretical analysis.


Input: It appears that THICA, unlike NDHPI and NHPI, is unsuitable for solvent-free catalysis or catalysis in aprotic solvents due to its favorable coexistent planar conformer.

THICA

NDHPI

NHPI


Input: Besides, the more remarkable catalytic efficiencies of NDHPI and THICA compared to NHPI can be ascribed to the lower barriers and the endothermicity in the H-abstraction processes by their radicals, especially by their multi-radicals which show stronger electron-withdrawing effects.

NDHPI

THICA

NHPI

H


Input: Furthermore, the generation of THICA radicals would be much feasible at high temperature without co-catalysts.

THICA


Input: This study provides a new perspective towards the rational design of reactive hydroxyimide organocatalysts for industrial applications.

hydroxyimide


Input: A novel adipose-specific gene deletion model demonstrates potential pitfalls of existing methods.