bluuebunny/crossref_metadata_2025_split huggingface dataset:
What's New in Antiplatelet and Anticoagulant Therapy Recommendations for Unstable Angina/Non–ST‐Elevation Myocardial Infarction
Authors: Wenger Nanette K. 
Published: October 2012

AbstractThis focused update addresses the use of the newly approved oral antiplatelet agents, prasugrel and ticagrelor, for the management of patients with UA/NSTEMI.The author has no funding, financial relationships, or conflicts of interest to disclose.
SIMinG‐1k: A thousand‐core simulator running on general‐purpose graphical processing units
Authors: Raghav Shivani , Marongiu Andrea , Pinto Christian , Ruggiero Martino , Atienza David , Benini Luca 
Published: October 2012

SUMMARYThis paper introduces SIMinG‐1k—a manycore simulator infrastructure. SIMinG‐1k is a graphics processing unit accelerated, parallel simulator for design‐space exploration of large‐scale manycore systems. It features an optimal trade‐off between modeling accuracy and simulation speed. Its main objectives are high performance, flexibility, and ability to simulate thousands of cores. SIMinG‐1k can model different architectures (currently, we support ARM (Available from: http://infocenter.arm.com/help/index.jsp?topic=/com.arm.doc.ddi0100i/index.html) and Intel x86) using two‐step approac where architecture specific front end is decoupled from a fast and parallel manycore virtual machine running on graphical processing unit platform. We evaluate the simulator for target architecture with up to 4096 cores. Our results demonstrate very high scalability and almost linear speedup with simulation of increasing number of cores.Copyright © 2012 John Wiley & Sons, Ltd.
Analyzing noise robustness of wide fan‐in dynamic logic gates under process variations
Authors: Frustaci Fabio , Lanuzza Marco , Perri Stefania , Corsonello Pasquale 
Published: October 2012

ABSTRACTWide fan‐in dynamic logic gates are difficult to design due to the large number of leaky evaluation paths connected to the dynamic node. Designers have to cope with their low noise tolerance further worsened by the effects of process parameter variation.In this paper, a novel analytical model is derived and validated to evaluate the noise robustness of wide fan‐in dynamic logic gates taking process variation effects into account. Experiments were performed using a commercial 45‐nm 1‐V CMOS technology, and the noise robustness in terms of unity noise gain (UNG) was evaluated for 16 and 32‐bit OR gates. Obtained results demonstrate that the proposed model is able to predict the mean value of the UNG with a maximum error of only 6.8%, whereas the difference between the predicted and simulated UNG yield is always lower than five percentage points. Copyright © 2012 John Wiley & Sons, Ltd.
The Role of Chemogenomics in the Pharmaceutical Industry
Authors: Bieler Michael , Koeppen Herbert 
Published: October 2012

Abstract

Preclinical Research

The goal of chemogenomics is the exploration of all possible interactions between compounds from the chemical space and targets from the biological space. This huge interaction matrix is only sparsely filled with experimental data but can be complemented by predicted values for selected ligand–target pairs. The prediction by computational chemogenomics uses the similarity principle that states that similar compounds have similar properties and that targets with similar binding sites bind similar ligands. Chemogenomics has a number of interesting applications, e.g. the prediction of the bioprofile of drugs including an assessment of possible adverse drug effects or the support of phenotypic screening by target fishing. This review focuses on applications of computational chemogenomics in pharmaceutical research and on the role that it plays in an industrial environment.
Infectomics Screening for Novel Antiviral Drug Targets
Authors: Liu Yuan , Yin Qi , Yuan Yao , Yang Wenyong , Jiang Chuangui , Huang Canhua 
Published: October 2012

Abstract

Preclinical Research

Infectomics, a novel way to globally and comprehensively understand the interactions between microbial pathogens and their hosts, has significantly expanded understanding of the microbial infections. The infectomics view of viral–host interactions on the viral perspective principally focuses on gene acquisition, deletion, and point mutation, while traditional antiviral drug discovery concentrates on viral encoding proteins. Recently, high‐throughput technologies, such as mass spectrometry‐based proteomics, activity‐based protein profiling, microarray analysis, yeast two‐hybrid assay, small interfering RNA screening, and micro RNA profiling, have been gradually employed in the research of virus–host interactions. Besides, signaling pathways and cellular processes involved in viral–host interactions provide new insights of infectomics in antiviral drug discovery. In this review, we summarize related infectomics approaches in the studies of virus–host interactions, which shed light on the development of novel antiviral drug targets screening.
Cell type–specific translational profiling in the Xenopus laevis retina
Authors: Watson F. L. , Mills E. A. , Wang X. , Guo C. , Chen D. F. , Marsh‐Armstrong N. 
Published: October 2012

AbstractBackground: Translating Ribosome Affinity Purification (TRAP), a method recently developed to generate cell type–specific translational profiles, relies on creating transgenic lines of animals in which a tagged ribosomal protein is placed under regulatory control of a cell type–specific promoter. An antibody is then used to affinity purify the tagged ribosomes so that cell type–specific mRNAs can be isolated from whole tissue lysates. Results: Here, cell type–specific transgenic lines were generated to enable TRAP studies for retinal ganglion cells and rod photoreceptors in the Xenopus laevis retina. Using real time quantitative PCR for assessing expression levels of cell type–specific mRNAs, the TRAP method was shown to selectively isolate mRNAs expressed in the targeted cell and was efficient at purifying mRNAs expressed at both high and low levels. Statistical measures used to distinguish cell type–specific RNAs from low level background and non‐specific RNAs showed TRAP to be highly effective in Xenopus. Conclusions: TRAP can be used to purify mRNAs expressed in rod photoreceptors and retinal ganglion cells in X. laevis. The generated transgenic lines will enable numerous studies into the development, disease, and injury of the X. laevis retina. Developmental Dynamics, 2012. © 2012 Wiley Periodicals, Inc.
In vivo evidence for unbiased ikaros retinal lineages using an ikaros‐cre mouse line driving clonal recombination
Authors: Tarchini Basile , Jolicoeur Christine , Cayouette Michel 
Published: October 2012

AbstractBackground: We showed previously that the transcription factor Ikaros is expressed in early but not late retinal progenitors cells (RPCs), and is necessary and sufficient for the production of early‐born neurons. Preliminary evidence using retinal explant cultures qualitatively suggested that Ikaros‐positive RPCs might share a common lineage with Ikaros‐negative RPCs. Results: To explore further this question in vivo in a quantitative manner, we generated BAC transgenic mouse lines expressing Cre recombinase under the regulatory elements of the Ikaros gene, and crossed them with Cre reporter lines. Different transgenic lines labeled a variable number of RPCs, resulting in either dense or sparse radial arrays of reporter‐positive progenies. Analysis of over 800 isolated cell arrays, which are most likely clones, confirmed that Ikaros‐expressing RPCs generate both early‐ and late‐born cell types in the same lineage, and that the overall cell composition of the arrays closely resembles that of the population of the mature retina. Interestingly, another sparse line did not label arrays, but appeared to specifically reflect Ikaros postmitotic expression in amacrine and ganglion cells. Conclusions: These mouse lines confirm the unbiased potential of the Ikaros lineage in vivo and provide novel tools for clonal lineage tracing and single neuron tracking in the retina. Developmental Dynamics, 2012. © 2012 Wiley Periodicals, Inc.
Analysis of postembryonic heart development and maturation in the zebrafish, Danio rerio
Authors: Singleman Corinna , Holtzman Nathalia G. 
Published: October 2012

AbstractBackground: Cardiac maturation is vital for animal survival and must occur throughout the animal's life. Zebrafish are increasingly used to model cardiac disease; however, little is known about how the cardiovascular system matures. We conducted a systematic analysis of cardiac maturation from larvae through to adulthood and assessed cardiac features influenced by genetic and environmental factors. Results: We identified a novel step in cardiac maturation, termed cardiac rotation, where the larval heart rotates into its final orientation within the thoracic cavity with the atrium placed behind the ventricle. This rotation is followed by linear ventricle growth and an increase in the angle between bulbous arteriosus and the ventricle. The ventricle transitions from a rectangle, to a triangle and ultimately a sphere that is significantly enveloped by the atrium. In addition, trabeculae are similarly patterned in the zebrafish and humans, both with muscular fingerlike projections and muscle bands that span the cardiac chamber. Of interest, partial loss of atrial contraction in myosin heavy chain 6 (myh6/weahu423/+) mutants result in the adult maintaining a larval cardiac form. Conclusions: These findings serve as a foundation for the study of defects in cardiovascular development from both genetic and environmental factors. Developmental Dynamics, 2012. © 2012 Wiley Periodicals, Inc.
Germline transgenesis of the chordate Ciona intestinalis with hyperactive variants of sleeping beauty transposable element
Authors: Hozumi Akiko , Mita Kaoru , Miskey Csaba , Mates Lajos , Izsvak Zsuzsanna , Ivics Zoltan , Satake Honoo , Sasakura Yasunori 
Published: October 2012

AbstractBackground: Transposon‐mediated transgenesis is an excellent method for creating stable transgenic lines and insertional mutants. In the chordate Ciona intestinalis, Minos is the only transposon that has been used as the tool for germline transformation. Adding another transposon system in this organism enables us to conduct genetic techniques which can only be realized with the use of two transposons. Results: In the present study, we found that another Tc1/mariner superfamily transposon, sleeping beauty (SB), retains sufficient activity for germline transformation of C. intestinalis. SB shows efficiencies of germline transformation, insertion into gene coding regions, and enhancer detection comparable to those of Minos. We have developed a system for the remobilization of SB copies in the C. intestinalis genome by using transgenic lines expressing SB transposase in the germ cells. With this system, we examined the manner of SB mobilization in the C. intestinalis genome. SB shows intrachromosomal transposition more frequently than Minos. Conclusions: SB‐based germline transformation and the establishment of a new method that uses its frequent intrachromosomal transposition will result in breakthroughs in genetic approaches that use C. intestinalis together with Minos. Developmental Dynamics 242:30–43, 2013. © 2012 Wiley Periodicals, Inc.
Transposable elements and viruses as factors in adaptation and evolution: an expansion and strengthening of theTE‐Thrust hypothesis
Authors: Oliver Keith R. , Greene Wayne K. 
Published: October 2012

AbstractIn addition to the strong divergent evolution and significant and episodic evolutionary transitions and speciation we previously attributed toTE‐Thrust, we have expanded the hypothesis to more fully account for the contribution of viruses toTE‐Thrust and evolution. The concept of symbiosis and holobiontic genomes is acknowledged, with particular emphasis placed on the creativity potential of the union of retroviral genomes with vertebrate genomes. Further expansions of theTE‐Thrust hypothesis are proposed regarding a fuller account of horizontal transfer ofTEs, the life cycle ofTEs, and also, in the case of a mammalian innovation, the contributions of retroviruses to the functions of the placenta. The possibility of drift byTEfamilies within isolated demes or disjunct populations, is acknowledged, and in addition, we suggest the possibility of horizontal transposon transfer into such subpopulations. “Adaptive potential” and “evolutionary potential” are proposed as the extremes of a continuum of “intra‐genomic potential” due toTE‐Thrust. Specific data is given, indicating “adaptive potential” being realized with regard to insecticide resistance, and other insect adaptations. In this regard, there is agreement betweenTE‐Thrust and the concept of adaptation by a change in allele frequencies. Evidence on the realization of “evolutionary potential” is also presented, which is compatible with the known differential survivals, and radiations of lineages. Collectively, these data further suggest the possibility, or likelihood, of punctuated episodes of speciation events and evolutionary transitions, coinciding with, and heavily underpinned by, intermittent bursts ofTEactivity.
Post‐Synthesis Grafting of Fluoropropyl Groups on SBA‐15 Type Ordered Mesoporous Silica
Authors: Benamor Taissire , Miesh Julien , Montégut Gaëtan , Nouali Habiba , Marichal Claire , Lebeau Bénédicte 
Published: October 2012

AbstractThe post‐synthesis grafting of fluoroalkyl groups has been performed to modulate the hydrophilic–hydrophobic balance of SBA‐15 type ordered mesoporous silica (OMS). The influence of the nature of the grafting agent and its structural and textural characteristics and the silanol content of the starting material on the hydrophobicity/hydrophilicity of the grafted material was investigated. If the parent material possessed high silanol content after calcination, high grafting yields and low CBET parameters were obtained.
Micro Solid‐Contact Ion‐Selective Electrode Using a Carbon Nanotube Tower as Ion‐to‐Electron Transducer and Conductive Substrate
Authors: Guo Xuefei , Meyung Timothy , Yun Yeoheung , Shanov Vesselin N. , Halsall H. Brian , Heineman William R. 
Published: October 2012

AbstractSolid contact (SC) ion‐selective electrodes (ISEs) have been recognized as the next generation of ISEs. In this work, the electrical conductivity and mechanical strength of a carbon nanotube (CNT) tower enable it to play the dual roles of transducer and substrate for micro SC‐ISEs. The electrode had a close to Nernstian slope of 35 mV/decade aCa2+, a linear range of four orders of magnitude of calcium ion activity (10−5.6 to 10−1.8 M), and a detection limit of 1.6×10−6 M. The simplified fabrication by a one‐step drop casting makes miniaturizing SC‐ISEs and fabricating sensor arrays easier to achieve.
A New Electrochemical Flow Cell for the Remote Sensing of Heavy Metals
Authors: Noyhouzer Tomer , Mandler Daniel 
Published: October 2012

AbstractRemote sensing is a fast developing field. The ability to detect various elements in secluded or inaccessible areas holds great opportunities. Here we present a new electrochemical flow cell which was developed as part of an autonomous flow system for measuring heavy metals in aquatic environments. The system was designed for remote sensing. Our system can utilize different commercially available electrodes and apply a range of electrochemical methods. The system was studied through both electrochemical experiments and simulation. The potential of the platform was demonstrated by analyzing seawater spiked with cadmium. Good agreement was found between our results and those obtained by ICP‐MS analysis.
Electrochemical Activation of the Natural Catalytic Cycle of Cytochrome P450s in Human Liver Microsomes
Authors: Wasalathanthri Dhanuka P. , Malla Spundana , Faria Ronaldo C. , Rusling James F. 
Published: October 2012

AbstractThe natural catalytic cycle of cytochrome (cyt) P450 enzymes in human liver microsome (HLM) films was activated electrochemically via the electron transfer sequence electrode→cyt P450 reductase (CPR)→cyt P450. Cyclic voltammograms for HLM films had midpoint potentials of −0.50 V vs. SCE at pH 7.4 characteristic of CPR, not cyt P450s. HLM and CPR microsomes without cyt P450s did not electrocatalytically reduce H2O2, and did not shift midpoint potential when CO was added, also indicating that the peaks do not correspond to iron heme cyt P450 enzymes. Electrochemical activation of the natural cyt P450 cycle for substrate conversion via CPR in HLM films was confirmed by catalytic electrolysis in an electrochemical microfluidic array designed to generate and detect reactive metabolites by measuring their reactivity with DNA.
Direct Voltammetric Determination of Total Iron with a Gold Microelectrode Ensemble
Authors: Zakharova E. A. , Elesova E. E. , Noskova G. N. , Lu M. , Compton R. G. 
Published: October 2012

AbstractThe behavior of the Fe(II)/(III) redox system at a Au microelectrode ensemble (Au‐MEE) based on a solid composite by means of direct and cyclic voltammetric analysis (VA) is reported. With a simple electrode activation and sample preparation, the influence of dissolved organic substances was eliminated, providing highly sensitive results. The analytical signal was based on the maximum cathodic current (I) of the first derivative (dI/dE), and iron determination within the 0.002–0.04 mg L−1 range was studied. A sensitive LOD (3σ) value of 0.7 µg L−1 for total iron concentration was calculated; total iron determination in different waters was shown.
Validation of nonlinear time history analysis models for single‐storey concentrically braced frames using full‐scale shake table tests
Authors: Goggins J. , Salawdeh S. 
Published: October 2012

SUMMARYThe concentrically braced frame (CBF) structure is one of the most efficient steel structural systems to resist earthquakes. This system can dissipate energy during earthquakes through braces, which are expected to yield in tension and buckle in compression, while all other elements such as columns, beams and connections are expected to behave elastically. In this paper, the performance of single‐storey CBFs is assessed with nonlinear time‐history analysis, where a robust numerical model that simulates the behaviour of shake table tests is developed. The numerical model of the brace element used in the analysis was calibrated using data measured in physical tests on brace members subjected to cyclic loading. The model is then validated by comparing predictions from nonlinear time‐history analysis to measured performance of brace members in full scale shake table tests. Furthermore, the sensitivity of the performance of the CBF to different earthquake ground motions is investigated by subjecting the CBF to eight ground motions that have been scaled to have similar displacement response spectra. The comparative assessments presented in this work indicate that these developed numerical models can accurately capture the salient features related to the seismic behaviour of CBFs. A good agreement is found between the performance of the numerical and physical models in terms of maximum displacement, base shear force, energy dissipated and the equivalent viscous damping. The energy dissipated and, more particular, the equivalent viscous damping, are important parameters required when developing an accurate displacement‐based design methodology for CBFs subjected to earthquake loading. In this study, a relatively good prediction of the equivalent viscous damping is obtained from the numerical model when compared with data measured during the shake table tests. However, it was found that already established equations to determine the equivalent viscous damping of CBFs may give closer values to those obtained from the physical tests. Copyright © 2012 John Wiley & Sons, Ltd.
Perfluorooctane sulfonate (PFOS) affects hormone receptor activity, steroidogenesis, and expression of endocrine-related genes in vitro and in vivo
Authors: Du Guizhen , Hu Jialei , Huang Hongyu , Qin Yufeng , Han Xiumei , Wu Di , Song Ling , Xia Yankai , Wang Xinru 
Published: October 2012

Abstract
Perfluorooctane sulfonate (PFOS) is a widespread and persistent chemical in the environment. We investigated the endocrine-disrupting effects of PFOS using a combination of in vitro and in vivo assays. Reporter gene assays were used to detect receptor-mediated (anti-)estrogenic, (anti-)androgenic, and (anti-)thyroid hormone activities. The effect of PFOS on steroidogenesis was assessed both at hormone levels in the supernatant and at expression levels of hormone-induced genes in the H295R cell. A zebrafish-based short-term screening method was developed to detect the effect of PFOS on endocrine function in vivo. The results indicate that PFOS can act as an estrogen receptor agonist and thyroid hormone receptor antagonist. Exposure to PFOS decreased supernatant testosterone (T), increased estradiol (E2) concentrations in H295R cell medium and altered the expression of several genes involved in steroidogenesis. In addition, PFOS increased early thyroid development gene (hhex and pax8) expression in a concentration-dependent manner, decreased steroidogenic enzyme gene (CYP17, CYP19a, CYP19b) expression, and changed the expression pattern of estrogen receptor production genes (esr1, esr2b) after 500 µg/L PFOS treatment in zebrafish embryos. These results indicate that PFOS has the ability to act as an endocrine disruptor both in vitro and in vivo by disrupting the function of nuclear hormone receptors, interfering with steroidogenesis, and altering the expression of endocrine-related genes in zebrafish embryo. Environ. Toxicol. Chem. 2013;32:353–360. © 2012 SETAC
Double‐blind, randomized study of extended release quetiapine fumarate (quetiapine XR) monotherapy in older patients with generalized anxiety disorder
Authors: Mezhebovsky Irina , Mägi Kairi , She Fahua , Datto Catherine , Eriksson Hans 
Published: October 2012

ObjectiveThe objective of the study was to evaluate once‐daily extended release quetiapine fumarate (quetiapine XR) monotherapy in older patients with generalized anxiety disorder (GAD).MethodsAn 11‐week (9‐week treatment; 2‐week posttreatment), randomized, double‐blind, placebo‐controlled study (D1448C00015) of flexibly‐dosed quetiapine XR (50–300 mg/day) or placebo conducted at 47 sites (Estonia, Poland, Russia, Ukraine, and USA) between September 2006 and April 2008. Patients (≥66 years) with DSM‐IV diagnosis of GAD, Hamilton Anxiety Rating Scale (HAM‐A) total score of ≥20 with item 1 (anxious mood) and 2 (tension) scores of ≥2, Clinical Global Impressions–Severity of Illness (CGI‐S) score of ≥4, and Montgomery Åsberg Depression Rating Scale (MADRS) total score of ≤16 were eligible for inclusion. Primary endpoint: week 9 change from randomization in HAM‐A total score.ResultsPatients were randomized to quetiapine XR (n = 223) or placebo (n = 227). At week 9, quetiapine XR significantly reduced HAM‐A total score versus placebo (least squares mean −14.97 versus −7.21; p < 0.001); symptom improvement with quetiapine XR versus placebo was significant at week 1 (p < 0.001). At week 9, quetiapine XR demonstrated significant benefits over placebo for HAM‐A response and remission rates, HAM‐A psychic and somatic cluster, MADRS total, CGI‐S, Pittsburgh Sleep Quality Index global, pain visual analog scale, and Quality of Life, Enjoyment and Satisfaction Questionnaire short form % maximum total scores and Clinical Global Impressions–Improvement (% patients with a score of 1/2) (all p < 0.001). Adverse events (>5% in either treatment group) included somnolence, dry mouth, dizziness, headache, and nausea.ConclusionsQuetiapine XR (50–300 mg/day) monotherapy is effective in the short term in improving symptoms of anxiety in older patients with GAD, with symptom improvement seen as early as week 1. Tolerability findings were generally consistent with the known profile of quetiapine. Copyright © 2012 John Wiley & Sons, Ltd.