1,132 research outputs found

    Status and prospects of computational fluid dynamics for unsteady transonic viscous flows

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    Applications of computational aerodynamics to aeronautical research, design, and analysis have increased rapidly over the past decade, and these applications offer significant benefits to aeroelasticians. The past developments are traced by means of a number of specific examples, and the trends are projected over the next several years. The crucial factors that limit the present capabilities for unsteady analyses are identified; they include computer speed and memory, algorithm and solution methods, grid generation, turbulence modeling, vortex modeling, data processing, and coupling of the aerodynamic and structural dynamic analyses. The prospects for overcoming these limitations are presented, and many improvements appear to be readily attainable. If so, a complete and reliable numerical simulation of the unsteady, transonic viscous flow around a realistic fighter aircraft configuration could become possible within the next decade. The possibilities of using artificial intelligence concepts to hasten the achievement of this goal are also discussed

    Statins do not directly inhibit the activity of major epigenetic modifying enzymes

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    The potential anticancer effects of statins—a widely used class of cholesterol loweringdrugs—has generated significant interest, as has the use of epigenetic modifying drugs such asHDAC and DNMT inhibitors. We set out to investigate the effect of statin drugs on epigeneticmodifications in multiple cell lines, including hepatocellular carcinoma, breast carcinoma, leukemicmacrophages, cervical adenocarcinoma, and insulin-secreting cells, as well as liver extracts fromstatin-treated C57B1/6J mice. Cells or cell extracts were treated with statins and with establishedepigenetic modulators, and HDAC, HAT, and DNMT activities were quantified. We also examinedhistone acetylation by immunoblotting. Statins altered neither HDAC nor HAT activity. Accordingly,acetylation of histones H3 and H4 was unchanged with statin treatment. However, statins tended toincrease DNMT activity. These results indicate that direct inhibition of the major classes of epigeneticmodifying enzymes, as previously reported elsewhere, is unlikely to contribute to any anticancereffects of statins. This study concerned global effects on epigenetic enzyme activities and histoneacetylation; whether statins influence epigenetic modifications in certain genomic regions, cannot beruled out and remains to be investigated

    Mutational and Structural Analysis of KIR3DL1 Reveals a Lineage-Defining Allotypic Dimorphism That Impacts Both HLA and Peptide Sensitivity

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    Killer Ig-like receptors (KIRs) control the activation of human NK cells via interactions with peptide-laden HLAs. KIR3DL1 is a highly polymorphic inhibitory receptor that recognizes a diverse array of HLA molecules expressing the Bw4 epitope, a group with multiple polymorphisms incorporating variants within the Bw4 motif. Genetic studies suggest that KIR3DL1 variation has functional significance in several disease states, including HIV infection. However, owing to differences across KIR3DL1 allotypes, HLA-Bw4, and associated peptides, the mechanistic link with biological outcome remains unclear. In this study, we elucidated the impact of KIR3DL1 polymorphism on peptide-laden HLA recognition. Mutational analysis revealed that KIR residues involved in water-mediated contacts with the HLA-presented peptide influence peptide binding specificity. In particular, residue 282 (glutamate) in the D2 domain underpins the lack of tolerance of negatively charged C-terminal peptide residues. Allotypic KIR3DL1 variants, defined by neighboring residue 283, displayed differential sensitivities to HLA-bound peptide, including the variable HLA-B*57:01-restricted HIV-1 Gag-derived epitope TW10. Residue 283, which has undergone positive selection during the evolution of human KIRs, also played a central role in Bw4 subtype recognition by KIR3DL1. Collectively, our findings uncover a common molecular regulator that controls HLA and peptide discrimination without participating directly in peptide-laden HLA interactions. Furthermore, they provide insight into the mechanics of interaction and generate simple, easily assessed criteria for the definition of KIR3DL1 functional groupings that will be relevant in many clinical applications, including bone marrow transplantation

    Physical drivers facilitating a toxigenic cyanobacterial bloom in a major Great Lakes tributary

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    The Maumee River is the primary source for nutrients fueling seasonal Microcystis-dominated blooms in western Lake Erie\u27s open waters though such blooms in the river are infrequent. The river also serves as source water for multiple public water systems and a large food services facility in northwest Ohio. On 20 September 2017, an unprecedented bloom was reported in the Maumee River estuary within the Toledo metropolitan area, which triggered a recreational water advisory. Here we (1) explore physical drivers likely contributing to the bloom\u27s occurrence, and (2) describe the toxin concentration and bacterioplankton taxonomic composition. A historical analysis using 10-years of seasonal river discharge, water level, and local wind data identified two instances when high-retention conditions occurred over ≥ 10 d in the Maumee River estuary: in 2016 and during the 2017 bloom. Observation by remote sensing imagery supported the advection of cyanobacterial cells into the estuary from the lake during 2017 and the lack of an estuary bloom in 2016 due to a weak cyanobacterial bloom in the lake. A rapid-response survey during the 2017 bloom determined levels of the cyanotoxins, specifically microcystins, in excess of recreational contact limits at sites within the lower 20 km of the river while amplicon sequencing found these sites were dominated by Microcystis. These results highlight the need to broaden our understanding of physical drivers of cyanobacterial blooms within the interface between riverine and lacustrine systems, particularly as such blooms are expected to become more prominent in response to a changing climate

    Sensorimotor supremacy: Investigating conscious and unconscious vision by masked priming

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    According to the sensorimotor supremacy hypothesis, conscious perception draws on motor action. In the present report, we will sketch two lines of potential development in the field of masking research based on the sensorimotor supremacy hypothesis. In the first part of the report, evidence is reviewed that masked, invisible stimuli can affect motor responses, attention shifts, and semantic processes. After the review of the corresponding evidence – so-called masked priming effects – an approach based on the sensorimotor supremacy hypothesis is detailed as to how the question of a unitary mechanism of unconscious vision can be pursued by masked priming studies. In the second part of the report, different models and theories of backward masking and masked priming are reviewed. Types of models based on the sensorimotor hypothesis are discussed that can take into account ways in which sensorimotor processes (reflected in masked priming effects) can affect conscious vision under backward masking conditions

    Study of interplanar binding in graphite by extended Thomas-Fermi theory

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    A model of a graphite crystal is used which consists of a set of parallel slabs of positive charge immersed in an electron sea. Each slab, about 1 Å wide, contains the charge of the nucleus and five electrons per carbon atom, homogeneously distributed in the volume of the slabs. The electron density in the region between slabs is calculated from Thomas-Fermi-Dirac theory including corrections for inhomogeneity to the kinetic energy and correlation energy. Also, a calculation is reported with the electron density obtained by a minimization of the Thomas-Fermi-Dirac-Kirzhnits functional. The results are in semiquantitative agreement with empirical data

    Studies of di-jet survival and surface emission bias in Au+Au collisions via angular correlations with respect to back-to-back leading hadrons

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    We report first results from an analysis based on a new multi-hadron correlation technique, exploring jet-medium interactions and di-jet surface emission bias at RHIC. Pairs of back-to-back high transverse momentum hadrons are used for triggers to study associated hadron distributions. In contrast with two- and three-particle correlations with a single trigger with similar kinematic selections, the associated hadron distribution of both trigger sides reveals no modification in either relative pseudo-rapidity or relative azimuthal angle from d+Au to central Au+Au collisions. We determine associated hadron yields and spectra as well as production rates for such correlated back-to-back triggers to gain additional insights on medium properties.Comment: By the STAR Collaboration. 6 pages, 2 figure
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