925 research outputs found

    An infinite stochastic model of social network formation

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    AbstractWe consider an infinite interacting particle system in which individuals choose neighbors according to evolving sets of probabilities. If x chooses y at some time, the effect is to increase the probability that y chooses x at later times. We characterize the extremal invariant measures for this process. In an extremal equilibrium, the set of individuals is partitioned into finite sets called stars, each of which includes a “center” that is always chosen by the other individuals in that set

    Systematic review of economic evaluations and cost analyses of guideline implementation strategies

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    Objectives To appraise the quality of economic studies undertaken as part of evaluations of guideline implementation strategies; determine their resources use; and recommend methods to improve future studies. Methods Systematic review of economic studies undertaken alongside robust study designs of clinical guideline implementation strategies published (1966-1998). Studies assessed against the BMJ economic evaluations guidelines for each stage of the guideline process (guideline development, implementation and treatment). Results 235 studies were identified, 63 reported some information on cost. Only 3 studies provided evidence that their guideline was effective and efficient. 38 reported the treatment costs only, 12 implementation and treatment costs, 11 implementation costs alone, and two guideline development, implementation and treatment costs. No study gave reasonably complete information on costs. Conclusions Very few satisfactory economic evaluations of guideline implementation strategies have been performed. Current evaluations have numerous methodological defects and rarely consider all relevant costs and benefits. Future evaluations should focus on evaluating the implementation of evidence based guidelines. Keywords: Cost-effectiveness analysis, physician (or health care professional) behaviour, practice guidelines, quality improvement, systematic review.Peer reviewedAuthor versio

    3D chromatin reprogramming primes human memory T<sub>H</sub>2 cells for rapid recall and pathogenic dysfunction

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    Memory T cells provide long-lasting defense responses through their ability to rapidly reactivate, but how they efficiently "recall" an inflammatory transcriptional program remains unclear. Here, we show that human CD4+ memory T helper 2 (TH2) cells carry a chromatin landscape synergistically reprogrammed at both one-dimensional (1D) and 3D levels to accommodate recall responses, which is absent in naive T cells. In memory TH2 cells, recall genes were epigenetically primed through the maintenance of transcription-permissive chromatin at distal (super)enhancers organized in long-range 3D chromatin hubs. Precise transcriptional control of key recall genes occurred inside dedicated topologically associating domains ("memory TADs"), in which activation-associated promoter-enhancer interactions were preformed and exploited by AP-1 transcription factors to promote rapid transcriptional induction. Resting memory TH2 cells from patients with asthma showed premature activation of primed recall circuits, linking aberrant transcriptional control of recall responses to chronic inflammation. Together, our results implicate stable multiscale reprogramming of chromatin organization as a key mechanism underlying immunological memory and dysfunction in T cells.</p

    Space Vehicle Terrestrial Environment Design Requirements Guidelines

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    The terrestrial environment is an important driver of space vehicle structural, control, and thermal system design. NASA is currently in the process of producing an update to an earlier Terrestrial Environment Guidelines for Aerospace Vehicle Design and Development Handbook. This paper addresses the contents of this updated handbook, with special emphasis on new material being included in the areas of atmospheric thermodynamic models, wind dynamics, atmospheric composition, atmospheric electricity, cloud phenomena, atmospheric extremes, and sea state. In addition, the respective engineering design elements are discussed relative to terrestrial environment inputs that require consideration. Specific lessons learned that have contributed to the advancements made in the application and awareness of terrestrial environment inputs for aerospace engineering applications are presented

    MAU2 and NIPBL variants impair the heterodimerization of the cohesin loader subunits and cause Cornelia de Lange syndrome

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    The NIPBL/MAU2 heterodimer loads cohesin onto chromatin. Mutations inNIPBLaccount for most cases ofthe rare developmental disorder Cornelia de Lange syndrome (CdLS). Here we report aMAU2 variant causing CdLS, a deletion of seven amino acids that impairs the interaction between MAU2 and the NIPBL N terminus.Investigating this interaction, we discovered that MAU2 and the NIPBL N terminus are largely dispensable fornormal cohesin and NIPBL function in cells with a NIPBL early truncating mutation. Despite a predicted fataloutcome of an out-of-frame single nucleotide duplication inNIPBL, engineered in two different cell lines,alternative translation initiation yields a form of NIPBL missing N-terminal residues. This form cannot interactwith MAU2, but binds DNA and mediates cohesin loading. Altogether, our work reveals that cohesin loading can occur independently of functional NIPBL/MAU2 complexes and highlights a novel mechanism protectiveagainst out-of-frame mutations that is potentially relevant for other genetic conditions

    Pattern formation in directional solidification under shear flow. I: Linear stability analysis and basic patterns

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    An asymptotic interface equation for directional solidification near the absolute stabiliy limit is extended by a nonlocal term describing a shear flow parallel to the interface. In the long-wave limit considered, the flow acts destabilizing on a planar interface. Moreover, linear stability analysis suggests that the morphology diagram is modified by the flow near the onset of the Mullins-Sekerka instability. Via numerical analysis, the bifurcation structure of the system is shown to change. Besides the known hexagonal cells, structures consisting of stripes arise. Due to its symmetry-breaking properties, the flow term induces a lateral drift of the whole pattern, once the instability has become active. The drift velocity is measured numerically and described analytically in the framework of a linear analysis. At large flow strength, the linear description breaks down, which is accompanied by a transition to flow-dominated morphologies, described in a companion paper. Small and intermediate flows lead to increased order in the lattice structure of the pattern, facilitating the elimination of defects. Locally oscillating structures appear closer to the instability threshold with flow than without.Comment: 20 pages, Latex, accepted for Physical Review
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