78 research outputs found

    Shift in the velocity of a front due to a cut-off

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    We consider the effect of a small cut-off epsilon on the velocity of a traveling wave in one dimension. Simulations done over more than ten orders of magnitude as well as a simple theoretical argument indicate that the effect of the cut-off epsilon is to select a single velocity which converges when epsilon tends to 0 to the one predicted by the marginal stability argument. For small epsilon, the shift in velocity has the form K(log epsilon)^(-2) and our prediction for the constant K agrees very well with the results of our simulations. A very similar logarithmic shift appears in more complicated situations, in particular in finite size effects of some microscopic stochastic systems. Our theoretical approach can also be extended to give a simple way of deriving the shift in position due to initial conditions in the Fisher-Kolmogorov or similar equations.Comment: 12 pages, 3 figure

    Isotopic Effect and Temperature Dependent Intramolecular Excitation Energy Transfer in a Model Donor-Acceptor Dyad

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    We consider here the non-adiabatic energy transfer dynamics for a model bi-chromophore system consisting of a perylenediimide unit linked to a ladder-type poly-(para-phenylene) oligomer. Starting from a semi-empirical parameterization of a model electron/phonon Hamiltonian, we compute the golden-rule rate for energy transfer from the LPPP5 donor to the PDI acceptor. Our results indicate that the non-adiabatic transfer is promoted by the out-of-plane wagging modes of the C-H bonds even though theses modes give little or no contribution to the Franck Condon factors in this system. We also predict a kinetic isotope effect of k(H)/k(D)=1.72.5k^{(H)}/k^{(D)} = 1.7 - 2.5 depending upon the temperature

    ALADIN is Required for the Production of Fertile Mouse Oocytes

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    Asymmetric cell divisions depend on the precise placement of the spindle apparatus. In mammalian oocytes, spindles assemble close to the cell's center, but chromosome segregation takes place at the cell periphery where half of the chromosomes are expelled into small, nondeveloping polar bodies at anaphase. By dividing so asymmetrically, most of the cytoplasmic content within the oocyte is preserved, which is critical for successful fertilization and early development. Recently we determined that the nucleoporin ALADIN participates in spindle assembly in somatic cells, and we have also shown that female mice homozygously null for ALADIN are sterile. In this study we show that this protein is involved in specific meiotic stages, including meiotic resumption, spindle assembly, and spindle positioning. In the absence of ALADIN, polar body extrusion is compromised due to problems in spindle orientation and anchoring at the first meiotic anaphase. ALADIN null oocytes that mature far enough to be fertilized in vitro are unable to support embryonic development beyond the two-cell stage. Overall, we find that ALADIN is critical for oocyte maturation and appears to be far more essential for this process than for somatic cell divisions

    Why Do Dolphins Carry Sponges?

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    Tool use is rare in wild animals, but of widespread interest because of its relationship to animal cognition, social learning and culture. Despite such attention, quantifying the costs and benefits of tool use has been difficult, largely because if tool use occurs, all population members typically exhibit the behavior. In Shark Bay, Australia, only a subset of the bottlenose dolphin population uses marine sponges as tools, providing an opportunity to assess both proximate and ultimate costs and benefits and document patterns of transmission. We compared sponge-carrying (sponger) females to non-sponge-carrying (non-sponger) females and show that spongers were more solitary, spent more time in deep water channel habitats, dived for longer durations, and devoted more time to foraging than non-spongers; and, even with these potential proximate costs, calving success of sponger females was not significantly different from non-spongers. We also show a clear female-bias in the ontogeny of sponging. With a solitary lifestyle, specialization, and high foraging demands, spongers used tools more than any non-human animal. We suggest that the ecological, social, and developmental mechanisms involved likely (1) help explain the high intrapopulation variation in female behaviour, (2) indicate tradeoffs (e.g., time allocation) between ecological and social factors and, (3) constrain the spread of this innovation to primarily vertical transmission

    Recommendations for the introduction of metagenomic high-throughput sequencing in clinical virology, part I:Wet lab procedure

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    Metagenomic high-throughput sequencing (mHTS) is a hypothesis-free, universal pathogen detection technique for determination of the DNA/RNA sequences in a variety of sample types and infectious syndromes. mHTS is still in its early stages of translating into clinical application. To support the development, implementation and standardization of mHTS procedures for virus diagnostics, the European Society for Clinical Virology (ESCV) Network on Next-Generation Sequencing (ENNGS) has been established. The aim of ENNGS is to bring together professionals involved in mHTS for viral diagnostics to share methodologies and experiences, and to develop application recommendations. This manuscript aims to provide practical recommendations for the wet lab procedures necessary for implementation of mHTS for virus diagnostics and to give recommendations for development and validation of laboratory methods, including mHTS quality assurance, control and quality assessment protocols

    Herpes simplex virus and rates of cognitive decline or whole brain atrophy in the Dominantly Inherited Alzheimer Network.

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    OBJECTIVE: To investigate whether herpes simplex virus type 1 (HSV-1) infection was associated with rates of cognitive decline or whole brain atrophy among individuals from the Dominantly Inherited Alzheimer Network (DIAN). METHODS: Among two subsets of the DIAN cohort (age range 19.6-66.6 years; median follow-up 3.0 years) we examined (i) rate of cognitive decline (N = 164) using change in mini-mental state examination (MMSE) score, (ii) rate of whole brain atrophy (N = 149), derived from serial MR imaging, calculated using the boundary shift integral (BSI) method. HSV-1 antibodies were assayed in baseline sera collected from 2009-2015. Linear mixed-effects models were used to compare outcomes by HSV-1 seropositivity and high HSV-1 IgG titres/IgM status. RESULTS: There was no association between baseline HSV-1 seropositivity and rates of cognitive decline or whole brain atrophy. Having high HSV-1 IgG titres/IgM was associated with a slightly greater decline in MMSE points per year (difference in slope - 0.365, 95% CI: -0.958 to -0.072), but not with rate of whole brain atrophy. Symptomatic mutation carriers declined fastest on both MMSE and BSI measures, however, this was not influenced by HSV-1. Among asymptomatic mutation carriers, rates of decline on MMSE and BSI were slightly greater among those who were HSV-1 seronegative. Among mutation-negative individuals, no differences were seen by HSV-1. Stratifying by APOE4 status yielded inconsistent results. INTERPRETATION: We found no evidence for a major role of HSV-1, measured by serum antibodies, in cognitive decline or whole brain atrophy among individuals at high risk of early-onset AD

    Crowdsourcing hypothesis tests: Making transparent how design choices shape research results

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    To what extent are research results influenced by subjective decisions that scientists make as they design studies? Fifteen research teams independently designed studies to answer fiveoriginal research questions related to moral judgments, negotiations, and implicit cognition. Participants from two separate large samples (total N > 15,000) were then randomly assigned to complete one version of each study. Effect sizes varied dramatically across different sets of materials designed to test the same hypothesis: materials from different teams renderedstatistically significant effects in opposite directions for four out of five hypotheses, with the narrowest range in estimates being d = -0.37 to +0.26. Meta-analysis and a Bayesian perspective on the results revealed overall support for two hypotheses, and a lack of support for three hypotheses. Overall, practically none of the variability in effect sizes was attributable to the skill of the research team in designing materials, while considerable variability was attributable to the hypothesis being tested. In a forecasting survey, predictions of other scientists were significantly correlated with study results, both across and within hypotheses. Crowdsourced testing of research hypotheses helps reveal the true consistency of empirical support for a scientific claim.</div

    Recommendations for the introduction of metagenomic high-throughput sequencing in clinical virology, part I: Wet lab procedure

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    Metagenomic high-throughput sequencing (mHTS) is a hypothesis-free, universal pathogen detection technique for determination of the DNA/RNA sequences in a variety of sample types and infectious syndromes. mHTS is still in its early stages of translating into clinical application. To support the development, implementation and standardization of mHTS procedures for virus diagnostics, the European Society for Clinical Virology (ESCV) Network on Next-Generation Sequencing (ENNGS) has been established. The aim of ENNGS is to bring together professionals involved in mHTS for viral diagnostics to share methodologies and experiences, and to develop application recommendations. This manuscript aims to provide practical recommendations for the wet lab procedures necessary for implementation of mHTS for virus diagnostics and to give recommendations for development and validation of laboratory methods, including mHTS quality assurance, control and quality assessment protocols

    Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

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    Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes
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