167 research outputs found

    Transposable elements donate lineage-specific regulatory sequences to host genomes

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    The evolutionary implications of transposable element (TE) influences on gene regulation are explored here. An historical perspective is presented to underscore the importance of TE influences on gene regulation with respect to both the discovery of TEs and the early conceptualization of their potential impact on host genome evolution. Evidence that points to a role for TEs in host gene regulation is reviewed, and comparisons between genome sequences are used to demonstrate the fact that TEs are particularly lineage-specific components of their host genomes. Consistent with these two properties of TEs, regulatory effects and evolutionary specificity, human-mouse genome wide sequence comparisons reveal that the regulatory sequences that are contributed by TEs are exceptionally lineage specific. This suggests a particular mechanism by which TEs may drive the diversification of gene regulation between evolutionary lineages

    Ancient pre-glacial erosion surfaces preserved beneath the West Antarctic Ice Sheet

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    Open access journalpresent ice-penetrating radar evidence for ancient (pre-glacial) and extensive erosion surfaces preserved beneath the upstream Institute and Möller ice streams, West Antarctica. Radar data reveal a smooth, laterally continuous, gently sloping topographic block, comprising two surfaces separated by a distinct break in slope. The erosion surfaces are preserved in this location due to the collective action of the Pirrit and Martin–Nash hills on ice sheet flow, resulting in a region of slow flowing, cold-based ice downstream of these major topographic barriers. Our analysis reveals that smooth, flat subglacial topography does not always correspond to regions of either present or former fast ice flow, as has previously been assumed. We discuss the potential origins of the erosion surfaces. Erosion rates across the surfaces are currently low, precluding formation via present-day glacial erosion. We suggest that fluvial or marine processes are most likely to have resulted in the formation of these surfaces, but we acknowledge that distinguishing between these processes with certainty requires further data.Natural Environment Research Council (NERC

    3D reconstruction of the fundus of a phantom eye through stereo imaging of slit lamp images

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    In the detection of glaucoma, the second leading cause of blindness worldwide, the alteration of the optic disc's morphology is a key clinical indicator. The current gold standard test, stereo funduscopy using stereo fundus cameras, is subjective. Quantitative devices exist but are prohibitively expensive. Work carried out elsewhere has demonstrated quantitative results from stereo matching fundus camera images. Building on this idea, the slit lamp microscope (a mainstay of eye diagnostics, present in practically all ophthalmology and optometry practices) has the potential to be used as a quantitative device. This study explored the feasibility of uncalibrated 3D reconstructions of retinal structures of a phantom eye's fundus using a slit lamp

    Lithium and potassium aminoalkoxides

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    Ice-flow structure and ice dynamic changes in the Weddell Sea sector of West Antarctica from radar-imaged internal layering

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    Recent studies have aroused concerns over the potential for ice draining the Weddell Sea sector of West Antarctica to figure more prominently in sea level contributions should buttressing from the Filchner-Ronne Ice Shelf diminish. To improve understanding of how ice stream dynamics there evolved through the Holocene, we interrogate radio echo sounding (RES) data from across the catchments of Institute and Möller Ice Streams (IIS and MIS), focusing especially on the use of internal layering to investigate ice-flow change. As an important component of this work, we investigate the influence that the orientation of the RES acquisition track with respect to ice flow exerts on internal layering and find that this influence is minimal unless a RES flight track parallels ice flow. We also investigate potential changes to internal layering characteristics with depth to search for important temporal transitions in ice-flow regime. Our findings suggest that ice in northern IIS, draining the Ellsworth Subglacial Highlands, has retained its present ice-flow configuration throughout the Holocene. This contrasts with less topographically constrained ice in southern IIS and much of MIS, whose internal layering evinces spatial changes to the configuration of ice flow over the past ∼10,000 years. Our findings confirm Siegert et al.'s (2013) inference that fast flow was diverted from Bungenstock Ice Rise during the Late Holocene and suggest that this may have represented just one component of wider regional changes to ice flow occurring across the IIS and MIS catchments as the West Antarctic Ice Sheet has thinned since the Last Glacial Maximum.NERC Antarctic Funding Initiativ

    UK Public Sector Information and Re-use Policy – A 2008 Analysis

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    INTRODUCTION: Earlier antiretroviral therapy (ART) initiation reduces HIV-1 incidence. This benefit may be offset by increased transmitted drug resistance (TDR), which could limit future HIV treatment options. We analyze the epidemiological impact and cost-effectiveness of strategies to reduce TDR. METHODS: We develop a deterministic mathematical model representing Kampala, Uganda, to predict the prevalence of TDR over a 10-year period. We then compare the impact on TDR and cost-effectiveness of: (1) introduction of pre-therapy genotyping; (2) doubling use of second-line treatment to 80% (50-90%) of patients with confirmed virological failure on first-line ART; and (3) increasing viral load monitoring from yearly to twice yearly. An intervention can be considered cost-effective if it costs less than three times the gross domestic product per capita per quality adjusted life year (QALY) gained, or less than 3420inUganda.RESULTS:TheprevalenceofTDRispredictedtorisefrom6.73420 in Uganda. RESULTS: The prevalence of TDR is predicted to rise from 6.7% (interquartile range [IQR] 6.2-7.2%) in 2014, to 6.8% (IQR 6.1-7.6%), 10.0% (IQR 8.9-11.5%) and 11.1% (IQR 9.7-13.0%) in 2024 if treatment is initiated at a CD4 <350, <500, or immediately, respectively. The absolute number of TDR cases is predicted to decrease 4.4-8.1% when treating earlier compared to treating at CD4 <350 due to the preventative effects of earlier treatment. Most cases of TDR can be averted by increasing second-line treatment (additional 7.1-10.2% reduction), followed by increased viral load monitoring (<2.7%) and pre-therapy genotyping (<1.0%). Only increasing second-line treatment is cost-effective, ranging from 1612 to 2234(IQR2234 (IQR 450-dominated) per QALY gained. CONCLUSIONS: While earlier treatment initiation will result in a predicted increase in the proportion of patients infected with drug-resistant HIV, the absolute numbers of patients infected with drug-resistant HIV is predicted to decrease. Increasing use of second-line treatment to all patients with confirmed failure on first-line therapy is a cost-effective approach to reduce TDR. Improving access to second-line ART is therefore a major priority

    Einstein's quantum theory of the monatomic ideal gas: non-statistical arguments for a new statistics

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    In this article, we analyze the third of three papers, in which Einstein presented his quantum theory of the ideal gas of 1924-1925. Although it failed to attract the attention of Einstein's contemporaries and although also today very few commentators refer to it, we argue for its significance in the context of Einstein's quantum researches. It contains an attempt to extend and exhaust the characterization of the monatomic ideal gas without appealing to combinatorics. Its ambiguities illustrate Einstein's confusion with his initial success in extending Bose's results and in realizing the consequences of what later became to be called Bose-Einstein statistics. We discuss Einstein's motivation for writing a non-combinatorial paper, partly in response to criticism by his friend Ehrenfest, and we paraphrase its content. Its arguments are based on Einstein's belief in the complete analogy between the thermodynamics of light quanta and of material particles and invoke considerations of adiabatic transformations as well as of dimensional analysis. These techniques were well-known to Einstein from earlier work on Wien's displacement law, Planck's radiation theory, and the specific heat of solids. We also investigate the possible role of Ehrenfest in the gestation of the theory.Comment: 57 pp

    The Drosophila melanogaster Genetic Reference Panel

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    A major challenge of biology is understanding the relationship between molecular genetic variation and variation in quantitative traits, including fitness. This relationship determines our ability to predict phenotypes from genotypes and to understand how evolutionary forces shape variation within and between species. Previous efforts to dissect the genotype-phenotype map were based on incomplete genotypic information. Here, we describe the Drosophila melanogaster Genetic Reference Panel (DGRP), a community resource for analysis of population genomics and quantitative traits. The DGRP consists of fully sequenced inbred lines derived from a natural population. Population genomic analyses reveal reduced polymorphism in centromeric autosomal regions and the X chromosome, evidence for positive and negative selection, and rapid evolution of the X chromosome. Many variants in novel genes, most at low frequency, are associated with quantitative traits and explain a large fraction of the phenotypic variance. The DGRP facilitates genotype-phenotype mapping using the power of Drosophila genetics
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