bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Hybrid Structure/Pharmacophore‐Based Virtual Screening Approach to Design Potential Leads: A Computer‐Aided Design of South African HIV‐1 Subtype C Protease Inhibitors
Authors: Soliman Mahmoud E. S. 
Published: March 2013

Abstract

Preclinical Research

Virtual screening is the computational mirror image of high‐throughput screening and refers to the in silico evaluation of the biological activity of different molecular entities. Various virtual screening strategies and workflows have been adopted to enhance the process of identification of potential hits. Structure‐based scoring relies solely on the interactions between the ligand and the target protein. Conversely, pharmacophore‐based scoring relies on the shape complementation of each ligand candidate to a three‐dimensional reference ligand. Herewith, we report a systematic integrated hybrid approach, along with the use of well‐defined physicochemical and biological filters, to enhance high‐ranking hit structures complementing the binding site architecture while also mimicking the three‐dimensional features of known active ligands.With a lack of experimental data on the South African HIV protease enzyme (C‐SA HIV PR), very limited research has been conducted to design inhibitors against this enzyme variant. In this paper, a focused integrated structure‐ and pharmacophore‐based virtual screening protocol is introduced to identify potential leads to assist toward designing potent inhibitors against the C‐SA PR variant. This rapid and systematic approach can potentially be implemented for the design and discovery of inhibitors against a wide range of biological targets.
Jagged1 is the major regulator of notch‐dependent cell fate in proximal airways
Authors: Zhang Shubing , Loch Amanda J. , Radtke Freddy , Egan Sean E. , Xu Keli 
Published: March 2013

ABSTRACTBackground: The Notch signaling pathway plays complex roles in developing lungs, including regulation of proximodistal fates, airway cell specification and differentiation. However, the specific Notch‐mediated signals involved in lung development remain unclear. Results: Here we report that Jagged1 is expressed in a subset of bronchial and bronchiolar epithelial cells, where it controls proximal airway cell fate and differentiation. In agreement with previous studies involving disruption of all Notch signaling, we found that deletion of Jagged1 in airway epithelium increased the number of ciliated cells at the expense of Clara cells, a phenotype associated with downregulation of Hes1. Deletion of Jagged1 also led to an increased number of pulmonary neuroendocrine cells (PNEC), suggesting that Jagged1/Notch signaling inhibits PNEC cell fate. As expected, Jagged1 deletion did not affect alveolar cell differentiation, although alveolar septation was impaired, likely an indirect effect of proximal airway defects. Finally, in the postnatal lung, Jagged1 deletion induced mucous metaplasia, accompanied by downregulation of Hes1 and Hes5. Conclusions: Our results demonstrate that Jagged1‐mediated Notch signaling regulates multiple cell fate decisions as well as differentiation in the respiratory system to coordinate lung development and to maintain a balance of airway cell types in adult life. Developmental Dynamics 242:678–686, 2013. © 2013 Wiley Periodicals, Inc.
On the relation between soil moisture dynamics and the geographical distribution of Culicoides imicola
Authors: Peters Jan , Conte Annamaria , Van doninck Jasper , Verhoest Niko E. C. , De Clercq Eva , Goffredo Maria , De Baets Bernard , Hendrickx Guy , Ducheyne Els 
Published: March 2013

ABSTRACTCulicoides imicola is the main biological vector in the transmission of the Bluetongue virus in the Mediterranean basin. Its geographical range is constrained by environmental characteristics, and soil moisture has been proposed as an important constraint because of its effect on C. imicola breeding habitat. The few field studies on breeding habitat of C. imicola indicate the favourability of (semi‐)moist habitat that is not flooded. Data on C. imicola in Calabria revealed the presence of C. imicola at the eastern Ionian coastal area and the absence at the greater part of the western Tyrrhenian coastal area. A spatially distributed soil moisture model was applied to obtain daily soil moisture estimates for Calabria and to assess the relationship between soil moisture and the particular C. imicola distribution at the study region. The temporal soil moisture pattern was not significantly different between locations of contrasting C. imicola occurrence. The monthly average volumetric soil moisture content, however, was found to differ substantially. Soil moisture conditions of the topsoil at locations of C. imicola presence were consistently wetter. Particularly in August, at the onset of the season of high C. imicola abundance, soil moisture was significantly higher at the presence sites and sustained the larval stages of the C. imicola life cycle. This study provides evidence that soil moisture imposes an important constraint on the geographical distribution of C. imicola. Soil moisture may therefore be considered as a key environmental variable for the delineation of suitable C. imicola habitat. Copyright © 2013 John Wiley & Sons, Ltd.
Aryl Bromides and Aryl Chlorides for the Direct Arylation of Benzylic Amines Mediated by Ruthenium(II)
Authors: Dastbaravardeh Navid , Schnürch Michael , Mihovilovic Marko D. 
Published: March 2013

AbstractThe ruthenium(II)‐catalyzed sp3 C–H bond arylation of benzylic amines with aryl halides is reported. In the present method, aryl iodides and, more importantly, also the cheaper aryl bromides and aryl chlorides can be applied as aryl sources. Additionally, the method does not require elaborate manipulations in a glove box and can be carried out in simple screw cap vials. Potassium pivalate proved to be beneficial for the transformation with aryl bromides or iodides as aryl source, but was not required for aryl chlorides. In the latter case, the addition of PPh3 led to high conversion. 3‐Methyl and 3‐phenyl pyridine were established as directing groups, and the substituent in the 3‐position represents a key structural feature for high conversion. The directing group can be cleaved after the transformation, which allows access to diarylmethylamines. Mechanistic studies were carried out and critically compared to mechanistic reports of related transformations.
Two‐dimensional nonlinear diffusive numerical simulation of geomorphic modifications to cinder cones
Authors: de' Michieli Vitturi Mattia , Arrowsmith J Ramón 
Published: March 2013

ABSTRACTThe temporal evolution of simple landforms such as cinder cones by nonlinear diffusive processes is studied through the use of a new 2D numerical model using well‐established and accurate numerical mathematics and high‐resolution digital elevation models (DEMs). Extending 1D (profile) nonlinear diffusion analyses used in cinder cone, hillslope and fault scarp evolution studies, we have implemented a 2D numerical model with a spatially and temporally varying sediment transport rate coefficient scaled nonlinearly by the ratio of local slope to critical slope. The high accuracy and efficient numerical implementation are documented in the paper and the MATLAB toolkit developed is used to solve for the developmentof an initial 2D cone form. First, we examine the nonlinear transport rule and suggest a refinement that accounts explicitly for flux at threshold slopes. We find that the maximum diffusion (necessarily introduced in the numerical model to avoid infinite rates) at the critical slope controls the final morphology, especially approaching steady state. Secondly, solving the landscape evolution problem in 2D enables a natural accounting for sediment flux convergence or divergence in the profile. Thirdly, the boundary behavior of a given landscape element controls much of what happens in that domain and so we allow for arbitrary flux magnitude or elevation boundary conditions. Fourthly, landscapes are heterogeneous in their surface cover and so we allow for spatially and temporally varying transport rate k and we permit an arbitrary vertical displacement field within the model domain. To test the new formulation for the nonlinear term, the effect of variable diffusivity k and the numerical schemes implemented, we apply the model to cinder cones built on the flanks of Mount Etna in 2001 and 2002–2003. We explore the effects of DEM resolution with data from the 2001 cone and the utility of spatially variable diffusivity to explain the variation in erosion measured by differencing repeat light detection and ranging (LIDAR) surveys gathered in 2004 and 2007 over the 2002–2003 cone complex. Copyright © 2013 John Wiley & Sons, Ltd.
Exploring geochemical controls on weathering and erosion of convex hillslopes: beyond the empirical regolith production function
Authors: Lebedeva Marina I. , Brantley Susan L. 
Published: March 2013

ABSTRACTLandscape curvature evolves in response to physical, chemical, and biological influences that cannot yet be quantified in models. Nonetheless, the simplest models predict the existence of equilibrium hillslope profiles. Here, we develop a model describing steady‐state regolith production caused by mineral dissolution on hillslopes which have attained an equilibrium parabolic profile. When the hillslope lowers at a constant rate, the rate of chemical weathering is highest at the ridgetop where curvature is highest and the ridge develops the thickest regolith. This result derives from inclusion of all the terms in the mathematical definition of curvature. Including these terms shows that the curvature of a parabolic hillslope profile varies with distance from the ridge. The hillslope model (meter‐scale) is similar to models of weathering rind formation (centimeter‐scale) where curvature‐driven solute transport causes development of the thickest rinds at highly curved clast corners. At the clast scale, models fit observations.Here, we similarly explore model predictions of the effect of curvature at the hillslope scale. The hillslope model shows that when erosion rates are small and vertical porefluid infiltration is moderate, the hill weathers at both ridge and valley in the erosive transport‐limited regime. For this regime, the reacting mineral is weathered away before it reaches the land surface: in other words, the model predicts completely developed element‐depth profiles at both ridge and valley. In contrast, when the erosion rate increases or porefluid velocity decreases, denudation occurs in the weathering‐limited regime. In this regime, the reacting mineral does not weather away before it reaches the land surface and simulations predict incompletely developed profiles at both ridge and valley. These predictions are broadly consistent with observations of completely developed element‐depth profiles along hillslopes denuding under erosive transport‐limitation but incompletely developed profiles along hillslopes denuding under weathering limitation in some field settings. Copyright © 2013 John Wiley & Sons, Ltd.
Assessment of the genotoxic potential of essential oil constituents by the Drosophila wing spot test
Authors: Mademtzoglou Despoina , Pavlidou Theodora , Bazioti Maria‐Georgia , Koutsonikou Chrysoula , Lioulia Elisavet , Akmoutsou Paraskevi , Drosopoulou Elena , Vokou Despoina , Mavragani‐Tsipidou Penelope 
Published: March 2013

ABSTRACTThe genotoxic activity of 15 essential oil constituents used as flavouring agents or cosmetic ingredients was assessed at four concentrations (2.5, 5.0, 7.5 and 10 µl/ml) using the Drosophila melanogaster (Meigen) somatic mutation and recombination test, also known as the wing spot test. Ten of the compounds tested here, namely d‐neomenthol, nerol, 1‐octen‐3‐ol, α‐terpineol, neryl acetate, terpinyl acetate, p‐cymene, α‐pinene, β‐pinene, α‐terpinene were found free of mutagenic or recombinogenic activity, at the applied concentrations. On the other hand, for (1R)‐(−)‐myrtenol and linalyl acetate, weak positive effects were exhibited even at the lowest concentration. For myrtenyl acetate, weakly positive effects were recorded at the high but not at the low concentrations. The two hydrocarbons, γ‐terpinene and terpinolene, showed no genotoxic activity at the low concentrations, but at the high ones they significantly increased the frequency of mutant clones. Results clearly demonstrate differences in activity of positional isomers such as α‐ and γ‐terpinene and terpinolene. Our data suggest the need for re‐evaluating the safety of suspect compounds with cross‐checked genotoxicity studies and at a range of different concentrations. Copyright © 2013 John Wiley & Sons, Ltd.
About the formulation, verification and validation of the hypersonic flow solver Eilmer
Authors: Gollan R.J. , Jacobs P.A. 
Published: March 2013

SUMMARYWe describe the formulation of the gas dynamics and high‐temperature thermochemical modules of the Eilmer code, an open‐source Navier–Stokes solver for transient compressible flow in two and three dimensions. The core gas dynamics formulation is based on finite‐volume cells, and the thermochemical effects are handled with specialised updating schemes that are coupled into the overall time‐stepping scheme. Verification of the code is explored via a number of case studies that use analytic and semi‐analytic solutions as comparison. These include both smooth and shocked flows and are used to demonstrate the order of spatial accuracy of the code. Cases include manufactured solutions for rather abstract inviscid and viscous flow, an idealised detonation wave supported by a curved body, and the transient flow of an idealised but high‐performance shock tube. Validation of the inviscid gas dynamics and thermochemical models is then explored using data from a selection of experimental studies. These studies include ballistic range experiments with chemically‐inert noble gases and high‐temperature chemically‐reacting air. These comparisons show that the code performs well and they provide a lesson in considering a range of experimental data rather than relying upon isolated data points for validation. These verification and validation cases are described in full detail and will be useful for other code developers of high‐temperature compressible flow solvers. Copyright © 2013 John Wiley & Sons, Ltd.
A Geometric Framework for Evaluating Rare Variant Tests of Association
Authors: Liu Keli , Fast Shannon , Zawistowski Matthew , Tintle Nathan L. 
Published: March 2013

ABSTRACTThe wave of next‐generation sequencing data has arrived. However, many questions still remain about how to best analyze sequence data, particularly the contribution of rare genetic variants to human disease. Numerous statistical methods have been proposed to aggregate association signals across multiple rare variant sites in an effort to increase statistical power; however, the precise relation between the tests is often not well understood. We present a geometric representation for rare variant data in which rare allele counts in case and control samples are treated as vectors in Euclidean space. The geometric framework facilitates a rigorous classification of existing rare variant tests into two broad categories: tests for a difference in the lengths of the case and control vectors, and joint tests for a difference in either the lengths or angles of the two vectors. We demonstrate that genetic architecture of a trait, including the number and frequency of risk alleles, directly relates to the behavior of the length and joint tests. Hence, the geometric framework allows prediction of which tests will perform best under different disease models. Furthermore, the structure of the geometric framework immediately suggests additional classes and types of rare variant tests. We consider two general classes of tests which show robustness to noncausal and protective variants. The geometric framework introduces a novel and unique method to assess current rare variant methodology and provides guidelines for both applied and theoretical researchers.
Association between depressive symptoms and metabolic syndrome in Japanese community‐dwelling older people: a cross‐sectional analysis from the baseline results of the Fujiwara‐kyo prospective cohort study
Authors: Morikawa Masayuki , Okamoto Nozomi , Kiuchi Kuniaki , Tomioka Kimiko , Iwamoto Junko , Harano Akihiro , Saeki Keigo , Fukusumi Masami , Hashimoto Kazumichi , Amano Nobuko , Hazaki Kan , Yanagi Motokazu , Iki Masayuki , Yamada Fumio , Kishimoto Toshifumi , Kurumatani Norio 
Published: March 2013

ObjectiveMetabolic syndrome contains many risks for medical diseases such as cardiovascular disease and diabetes, which might precipitate depressive symptoms in the older people. However, the association between depressive symptoms and metabolic syndrome in Japanese community‐dwelling older people is unclear. This study was performed to answer this important question.MethodsCross‐sectional analyses were performed on 3796 community‐dwelling independent older people (≥65 years, 1911 men and 1885 women) from the 2007–2008 baseline examination of the Fujiwara‐kyo study, a prospective cohort study on successful aging. Depressive symptoms were assessed using the 15‐item short form of the Geriatric Depression Scale and metabolic syndrome was defined according to the 2005 International Diabetes Federation. Covariates were social supports, negative life events, health behavior, education, cognitive function, anthropometric status, and others. Multiple logistic regression analyses were performed to determine the relationships between depressive symptoms and these variables.ResultsThe prevalence of depressive symptoms (Geriatric Depression Scale‐15 ≥6) and metabolic syndrome were 14.8% and 16.6%, respectively. Significant protective factors against depressive symptoms were higher education, more opportunity for drinking of alcohol, better social supports, and more walking daily. Metabolic syndrome was statistically associated with depressive symptoms (adjusted odds ratio = 1.32, 95% confidence interval = 1.03–1.68). Other risk factors significantly associated with depressive symptoms were sleep disturbance, visual or hearing impairment, and negative life events.ConclusionsThe present study showed an association between metabolic syndrome and depressive symptoms in ambulatory Japanese older people, as in western countries.
Sensitivity of summer precipitation to tropical sea surface temperatures over East Asia in the GRIMs GMP
Authors: Chang Eun‐Chul , Yeh Sang‐Wook , Hong Song‐You , Wu Renguang 
Published: March 2013

AbstractIn this study, uncoupled atmospheric general circulation model experiments are conducted to examine the sensitivity of tropical Ocean basins from the Indian Ocean to the tropical Pacific Ocean on the summer precipitation variability over East Asia. It is remarkable that the Indian Ocean basin sea surface temperature (SST) and the tropical Pacific basin SST act on summer precipitation variability over Northeast Asia and southern China quite differently. That is, SST warming in the Indian Ocean largely contributes to the increase in the amount of summer precipitation over East Asia, which is in contrast to the warming of the western tropical Pacific Ocean. Our further analysis indicates that an altered large‐scale atmospheric circulation over the western tropical Pacific contributes to contrasting atmospheric motion over East Asia due to the tropics‐East Asia teleconnections, which results in changes in the amount of summer precipitation due to the warming of the Indian and western tropical Pacific Oceans.
On the impact angle of Hurricane Sandy's New Jersey landfall
Authors: Hall Timothy M. , Sobel Adam H. 
Published: March 2013

AbstractHurricane Sandy's track crossed the New Jersey coastline at an angle closer to perpendicular than any previous hurricane in the historic record, one of the factors contributing to record‐setting peak‐water levels in parts of New Jersey and New York. To estimate the occurrence rate of Sandy‐like tracks, we use a stochastic model built on historical hurricane data from the entire North Atlantic to generate a large sample of synthetic hurricanes. From this synthetic set we calculate that under long‐term average climate conditions, a hurricane of Sandy's intensity or greater (category 1+) makes NJ landfall at an angle at least as close to perpendicular as Sandy's at an average annual rate of 0.0014 yr–1 (95% confidence range 0.0007 to 0.0023); i.e., a return period of 714 years (95% confidence range 435 to 1429).
Talent or Not? Employee Reactions to Talent Identification
Authors: Björkman Ingmar , Ehrnrooth Mats , Mäkelä Kristiina , Smale Adam , Sumelius Jennie 
Published: March 2013

AbstractIn this article, we examine the effect of talent identification on employee attitudes. Building on social exchange theory, we analyze the association between employees' perceptions about whether or not they have been formally identified as “talent” and the following attitudinal outcomes: commitment to increasing performance demands, building skills, and supporting strategic priorities; identification with the unit and the multinational enterprise; and turnover intentions. Our analyses of 769 managers and professionals in nine Nordic multinational corporations reveal a number of differences between employees who perceive that they have been identified as “talent” and those who either perceive that they have not been identified or do not know whether they have been identified. We found only limited differences between the two latter categories.
Internal Commitment or External Collaboration? The Impact of Human Resource Management Systems on Firm Innovation and Performance
Authors: Zhou Yu , Hong Ying , Liu Jun 
Published: March 2013

AbstractComplementing previous research that showed a positive effect of general human resource management (HRM) systems on general firm performance, this article undertakes an integrative approach to compare the main effects and examine the interaction effects of two particular HRM systems on influencing firm innovation and performance. Using data from 179 organizations in China, we found that both the commitment‐oriented system, which emphasized internal cohesiveness, and the collaboration‐oriented system, which was intended to build external connections, contributed to firm innovation and, subsequently, bottom‐line performance. We also found an attenuated interaction between the two HRM systems in predicting firm innovation. We employed a mediated‐moderation path model to extricate the relationships. Results suggested that organizations that implemented both HRM systems to promote innovation might face ambidexterity challenges. Ideas for future research and practical implications are discussed.