261 research outputs found

    High-order Discretization of a Gyrokinetic Vlasov Model in Edge Plasma Geometry

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    We present a high-order spatial discretization of a continuum gyrokinetic Vlasov model in axisymmetric tokamak edge plasma geometries. Such models describe the phase space advection of plasma species distribution functions in the absence of collisions. The gyrokinetic model is posed in a four-dimensional phase space, upon which a grid is imposed when discretized. To mitigate the computational cost associated with high-dimensional grids, we employ a high-order discretization to reduce the grid size needed to achieve a given level of accuracy relative to lower-order methods. Strong anisotropy induced by the magnetic field motivates the use of mapped coordinate grids aligned with magnetic flux surfaces. The natural partitioning of the edge geometry by the separatrix between the closed and open field line regions leads to the consideration of multiple mapped blocks, in what is known as a mapped multiblock (MMB) approach. We describe the specialization of a more general formalism that we have developed for the construction of high-order, finite-volume discretizations on MMB grids, yielding the accurate evaluation of the gyrokinetic Vlasov operator, the metric factors resulting from the MMB coordinate mappings, and the interaction of blocks at adjacent boundaries. Our conservative formulation of the gyrokinetic Vlasov model incorporates the fact that the phase space velocity has zero divergence, which must be preserved discretely to avoid truncation error accumulation. We describe an approach for the discrete evaluation of the gyrokinetic phase space velocity that preserves the divergence-free property to machine precision

    The Awesome Power of Yeast Evolutionary Genetics: New Genome Sequences and Strain Resources for the Saccharomyces sensu stricto Genus

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    High-quality, well-annotated genome sequences and standardized laboratory strains fuel experimental and evolutionary research. We present improved genome sequences of three species of Saccharomyces sensu stricto yeasts: S. bayanus var. uvarum (CBS 7001), S. kudriavzevii (IFO 1802T and ZP 591), and S. mikatae (IFO 1815T), and describe their comparison to the genomes of S. cerevisiae and S. paradoxus. The new sequences, derived by assembling millions of short DNA sequence reads together with previously published Sanger shotgun reads, have vastly greater long-range continuity and far fewer gaps than the previously available genome sequences. New gene predictions defined a set of 5261 protein-coding orthologs across the five most commonly studied Saccharomyces yeasts, enabling a re-examination of the tempo and mode of yeast gene evolution and improved inferences of species-specific gains and losses. To facilitate experimental investigations, we generated genetically marked, stable haploid strains for all three of these Saccharomyces species. These nearly complete genome sequences and the collection of genetically marked strains provide a valuable toolset for comparative studies of gene function, metabolism, and evolution, and render Saccharomyces sensu stricto the most experimentally tractable model genus. These resources are freely available and accessible through www.SaccharomycesSensuStricto.org

    A three-dimensional model for the probabilistic intergranular failure of polycrystalline arrays

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    A three-dimensional grain model, in which the grains are represented by regular truncated octahedra, has been developed to study probabilistic time-dependent intergranular failure in polycrystalline arrays. In this model, grain boundary facets are assumed to fail randomly in time, as a function of the facet normal stress. A simple approximate method for calculating the load shed by failed facets and a reasonable choice of failure criterion complete the model. This leads to a conceptually simple, but computationally complex, model capable of handling assemblages consisting of relatively large numbers (> 5000) of grains. The predicted scatter in the times-to-failure and the variation in number of failed facets with time are in quite reasonable agreement with available experimental data.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/49082/2/ms6302.pd

    Evolution of a Membrane Protein Regulon in Saccharomyces

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    Expression variation is widespread between species. The ability to distinguish regulatory change driven by natural selection from the consequences of neutral drift remains a major challenge in comparative genomics. In this work, we used observations of mRNA expression and promoter sequence to analyze signatures of selection on groups of functionally related genes in Saccharomycete yeasts. In a survey of gene regulons with expression divergence between Saccharomyces cerevisiae and S. paradoxus, we found that most were subject to variation in trans-regulatory factors that provided no evidence against a neutral model. However, we identified one regulon of membrane protein genes controlled by unlinked cis- and trans-acting determinants with coherent effects on gene expression, consistent with a history of directional, nonneutral evolution. For this membrane protein group, S. paradoxus alleles at regulatory loci were associated with elevated expression and altered stress responsiveness relative to other yeasts. In a phylogenetic comparison of promoter sequences of the membrane protein genes between species, the S. paradoxus lineage was distinguished by a short branch length, indicative of strong selective constraint. Likewise, sequence variants within the S. paradoxus population, but not across strains of other yeasts, were skewed toward low frequencies in promoters of genes in the membrane protein regulon, again reflecting strong purifying selection. Our results support a model in which a distinct expression program for the membrane protein genes in S. paradoxus has been preferentially maintained by negative selection as the result of an increased importance to organismal fitness. These findings illustrate the power of integrating expression- and sequence-based tests of natural selection in the study of evolutionary forces that underlie regulatory change

    Natural law, non-voluntary euthanasia, and public policy

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    © 2019 by Emerald Publishing Limited. Natural Law philosophy asserts that there are universally binding and universally evident principles that can be determined to guide the actions of persons. Moreover, many of these principles have been enshrined in both statute and common law, thus ensuring their saliency for staff and institutions charged with palliative care. The authors examine the often emotive and politicized matter of (non-voluntary) euthanasia – acts or omissions made with the intent of causing or hastening death – with reference to Natural Law philosophy. This leads us to propose a number of important public policy remedies to ensure dignity in dying for the patient, and their associates

    The future of fungi: threats and opportunities

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    The fungal kingdom represents an extraordinary diversity of organisms with profound impacts across animal, plant, and ecosystem health. Fungi simultaneously support life, by forming beneficial symbioses with plants and producing life-saving medicines, and bring death, by causing devastating diseases in humans, plants, and animals. With climate change, increased antimicrobial resistance, global trade, environmental degradation, and novel viruses altering the impact of fungi on health and disease, developing new approaches is now more crucial than ever to combat the threats posed by fungi and to harness their extraordinary potential for applications in human health, food supply, and environmental remediation. To address this aim, the Canadian Institute for Advanced Research (CIFAR) and the Burroughs Wellcome Fund convened a workshop to unite leading experts on fungal biology from academia and industry to strategize innovative solutions to global challenges and fungal threats. This report provides recommendations to accelerate fungal research and highlights the major research advances and ideas discussed at the meeting pertaining to 5 major topics: (1) Connections between fungi and climate change and ways to avert climate catastrophe; (2) Fungal threats to humans and ways to mitigate them; (3) Fungal threats to agriculture and food security and approaches to ensure a robust global food supply; (4) Fungal threats to animals and approaches to avoid species collapse and extinction; and (5) Opportunities presented by the fungal kingdom, including novel medicines and enzymes

    cGAL, a temperature-robust GAL4–UAS system for Caenorhabditis elegans

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    The GAL4–UAS system is a powerful tool for manipulating gene expression, but its application in Caenorhabditis elegans has not been described. Here we systematically optimize the system's three main components to develop a temperature-optimized GAL4–UAS system (cGAL) that robustly controls gene expression in C. elegans from 15 to 25 °C. We demonstrate this system's utility in transcriptional reporter analysis, site-of-action experiments and exogenous transgene expression; and we provide a basic driver and effector toolkit
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