2,726 research outputs found

    Anomalous material-dependent transport of focused, laser-driven proton beams.

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    Intense lasers can accelerate protons in sufficient numbers and energy that the resulting beam can heat materials to exotic warm (10 s of eV temperature) states. Here we show with experimental data that a laser-driven proton beam focused onto a target heated it in a localized spot with size strongly dependent upon material and as small as 35 μm radius. Simulations indicate that cold stopping power values cannot model the intense proton beam transport in solid targets well enough to match the large differences observed. In the experiment a 74 J, 670 fs laser drove a focusing proton beam that transported through different thicknesses of solid Mylar, Al, Cu or Au, eventually heating a rear, thin, Au witness layer. The XUV emission seen from the rear of the Au indicated a clear dependence of proton beam transport upon atomic number, Z, of the transport layer: a larger and brighter emission spot was measured after proton transport through the lower Z foils even with equal mass density for supposed equivalent proton stopping range. Beam transport dynamics pertaining to the observed heated spot were investigated numerically with a particle-in-cell (PIC) code. In simulations protons moving through an Al transport layer result in higher Au temperature responsible for higher Au radiant emittance compared to a Cu transport case. The inferred finding that proton stopping varies with temperature in different materials, considerably changing the beam heating profile, can guide applications seeking to controllably heat targets with intense proton beams

    Evaluating predictive pharmacogenetic signatures of adverse events in colorectal cancer patients treated with fluoropyrimidines

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    The potential clinical utility of genetic markers associated with response to fluoropyrimidine treatment in colorectal cancer patients remains controversial despite extensive study. Our aim was to test the clinical validity of both novel and previously identified markers of adverse events in a broad clinical setting. We have conducted an observational pharmacogenetic study of early adverse events in a cohort study of 254 colorectal cancer patients treated with 5-fluorouracil or capecitabine. Sixteen variants of nine key folate (pharmacodynamic) and drug metabolising (pharmacokinetic) enzymes have been analysed as individual markers and/or signatures of markers. We found a significant association between TYMP S471L (rs11479) and early dose modifications and/or severe adverse events (adjusted OR = 2.02 [1.03; 4.00], p = 0.042, adjusted OR = 2.70 [1.23; 5.92], p = 0.01 respectively). There was also a significant association between these phenotypes and a signature of DPYD mutations (Adjusted OR = 3.96 [1.17; 13.33], p = 0.03, adjusted OR = 6.76 [1.99; 22.96], p = 0.002 respectively). We did not identify any significant associations between the individual candidate pharmacodynamic markers and toxicity. If a predictive test for early adverse events analysed the TYMP and DPYD variants as a signature, the sensitivity would be 45.5 %, with a positive predictive value of just 33.9 % and thus poor clinical validity. Most studies to date have been under-powered to consider multiple pharmacokinetic and pharmacodynamic variants simultaneously but this and similar individualised data sets could be pooled in meta-analyses to resolve uncertainties about the potential clinical utility of these markers

    New ophthalmosaurid ichthyosaurs from the European lower cretaceous demonstrate extensive ichthyosaur survival across the Jurassic–Cretaceous boundary

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    Background Ichthyosauria is a diverse clade of marine amniotes that spanned most of the Mesozoic. Until recently, most authors interpreted the fossil record as showing that three major extinction events affected this group during its history: one during the latest Triassic, one at the Jurassic–Cretaceous boundary (JCB), and one (resulting in total extinction) at the Cenomanian-Turonian boundary. The JCB was believed to eradicate most of the peculiar morphotypes found in the Late Jurassic, in favor of apparently less specialized forms in the Cretaceous. However, the record of ichthyosaurs from the Berriasian–Barremian interval is extremely limited, and the effects of the end-Jurassic extinction event on ichthyosaurs remains poorly understood. Methodology/Principal Findings Based on new material from the Hauterivian of England and Germany and on abundant material from the Cambridge Greensand Formation, we name a new ophthalmosaurid, Acamptonectes densus gen. et sp. nov. This taxon shares numerous features with Ophthalmosaurus, a genus now restricted to the Callovian–Berriasian interval. Our phylogenetic analysis indicates that Ophthalmosauridae diverged early in its history into two markedly distinct clades, Ophthalmosaurinae and Platypterygiinae, both of which cross the JCB and persist to the late Albian at least. To evaluate the effect of the JCB extinction event on ichthyosaurs, we calculated cladogenesis, extinction, and survival rates for each stage of the Oxfordian–Barremian interval, under different scenarios. The extinction rate during the JCB never surpasses the background extinction rate for the Oxfordian–Barremian interval and the JCB records one of the highest survival rates of the interval. Conclusions/Significance There is currently no evidence that ichthyosaurs were affected by the JCB extinction event, in contrast to many other marine groups. Ophthalmosaurid ichthyosaurs remained diverse from their rapid radiation in the Middle Jurassic to their total extinction at the beginning of the Late Cretaceous

    Klebsiella pneumoniae is able to trigger epithelial-mesenchymal transition process in cultured airway epithelial cells

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    The ability of some bacterial pathogens to activate Epithelial-Mesenchymal Transition normally is a consequence of the persistence of a local chronic inflammatory response or depends on a direct interaction of the pathogens with the host epithelial cells. In this study we monitored the abilities of the K. pneumoniae to activate the expression of genes related to EMT-like processes and the occurrence of phenotypic changes in airway epithelial cells during the early steps of cell infection. We describe changes in the production of intracellular reactive oxygen species and increased HIF-1α mRNA expression in cells exposed to K. pneumoniae infection. We also describe the upregulation of a set of transcription factors implicated in the EMT processes, such as Twist, Snail and ZEB, indicating that the morphological changes of epithelial cells already appreciable after few hours from the K. pneumoniae infection are tightly regulated by the activation of transcriptional pathways, driving epithelial cells to EMT. These effects appear to be effectively counteracted by resveratrol, an antioxidant that is able to exert a sustained scavenging of the intracellular ROS. This is the first report indicating that strains of K. pneumoniae may promote EMT-like programs through direct interaction with epithelial cells without the involvement of inflammatory cells

    A Small Conductance Calcium-Activated K<sup>+</sup> Channel in C. elegans, KCNL-2, Plays a Role in the Regulation of the Rate of Egg-Laying

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    In the nervous system of mice, small conductance calcium-activated potassium (SK) channels function to regulate neuronal excitability through the generation of a component of the medium afterhyperpolarization that follows action potentials. In humans, irregular action potential firing frequency underlies diseases such as ataxia, epilepsy, schizophrenia and Parkinson's disease. Due to the complexity of studying protein function in the mammalian nervous system, we sought to characterize an SK channel homologue, KCNL-2, in C. elegans, a genetically tractable system in which the lineage of individual neurons was mapped from their early developmental stages. Sequence analysis of the KCNL-2 protein reveals that the six transmembrane domains, the potassium-selective pore and the calmodulin binding domain are highly conserved with the mammalian homologues. We used widefield and confocal fluorescent imaging to show that a fusion construct of KCNL-2 with GFP in transgenic lines is expressed in the nervous system of C. elegans. We also show that a KCNL-2 null strain, kcnl-2(tm1885), demonstrates a mild egg-laying defective phenotype, a phenotype that is rescued in a KCNL-2-dependent manner. Conversely, we show that transgenic lines that overexpress KCNL-2 demonstrate a hyperactive egg-laying phenotype. In this study, we show that the vulva of transgenic hermaphrodites is highly innervated by neuronal processes and by the VC4 and VC5 neurons that express GFP-tagged KCNL-2. We propose that KCNL-2 functions in the nervous system of C. elegans to regulate the rate of egg-laying. © 2013 Chotoo et al

    Phylogenomics illuminates the backbone of the Myriapoda Tree of Life and reconciles morphological and molecular phylogenies

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    © The Author(s) 2017 This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. The attached file is the published version of the article

    The Impact of Cross Cultural Communication on Collective Efficacy in NCAA Basketball Teams

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    This research contributes to the knowledge and theory on cross cultural communication by investigating the impact of cross cultural communication competence on the collective efficacy of multicultural National Collegiate Athletic Association basketball teams. Data was collected from 140 U.S. National Collegiate Athletic Association basketball coaches via the Cross Cultural Communication Competence Questionnaire and the Collective Efficacy Questionnaire for Sports. Principle component analysis was conducted on the data, revealing that the cross cultural communication competence and collective efficacy of basketball teams are multidimensional. The hypothesized relationship between cross cultural communication competence and collective efficacy was confirmed and statistically measured through regression analysis. It was found that four of the cross cultural communication competence dimensions produced by the principle component analysis exhibited a significant positive relationship with one of the two dimensions within collective efficacy. Given the well-supported relationship between collective efficacy and team performance in business, this study produces important implications for scholars and practitioners working with multicultural sporting teams

    Occupational Exposure to Endocrine-Disrupting Chemicals and Birth Weight and Length of Gestation: A European Meta-Analysis

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    BACKGROUND: Women of reproductive age can be exposed to endocrine-disrupting chemicals (EDCs) at work and exposure to EDCs in pregnancy may affect fetal growth. OBJECTIVES: We assessed whether maternal occupational exposure to EDCs during pregnancy as classified by application of a job exposure matrix was associated with birth weight, term low birth weight (LBW), length of gestation, and preterm delivery. METHODS: Using individual participant data from 133,957 mother-child pairs in 13 European cohorts spanning births from 1994 to 2011, we linked maternal job titles with exposure to 10 EDC groups as assessed through a job exposure matrix. For each group, we combined the two levels of exposure categories (possible and probable) and compared birth outcomes with the unexposed group (exposure unlikely). We performed meta-analyses of cohort-specific estimates. RESULTS: Eleven percent of pregnant women were classified as exposed to EDCs at work during pregnancy based on job title. Classification of exposure to one or more EDC group was associated with an increased risk of term LBW (OR 1.25, 95%CI 1.04, 1.49), as were most specific EDC groups; this association was consistent across cohorts. Further, the risk increased with increasing number of EDC groups (OR 2.11 95%CI 1.10, 4.06 for exposure to 4 or more EDC groups). There were few associations (p < 0.05) with the other outcomes; women holding job titles classified as exposed to bisphenol A or brominated flame retardants were at higher risk for longer length of gestation. CONCLUSION: Results from our large population-based birth cohort design indicate that employment during pregnancy in occupations classified as possibly or probably exposed to EDCs was associated with an increased risk of term LBW

    Quinine doped hybrid sol-gel coatings for wave guiding and optical applications

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    Pure and quinine doped silica coatings have been prepared over sodalime glasses. The coatings were consolidated at low temperature (range 60-180 A degrees C) preserving optical activity of quinine molecule. We designed a device to test the guiding properties of the coatings. We confirmed with this device that light injected in pure silica coatings is guided over distances of meters while quinine presence induces isotropic photoluminescence. With the combined use of both type of coatings, it is possible to design light guiding devices and illuminate regions in glass elements without electronic circuits
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