905 research outputs found

    Static aeroelastic analysis of a three-dimensional generic wing

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    A continuation of research on the static aeroelastic analysis of a generic wing configuration is presented. Results of the study of the asymmetric oblique wing model developed by Rockwell International, in conjunction with the NASA Oblique Wing Research Aircraft Program, are reported. The capability to perform static aeroelastic analyses of an oblique wing at arbitrary skew positions is demonstrated by applying the MSC/NASTRAN static analysis scheme modified by the aerodynamic influence coefficient matrix created by the NASA Ames aerodynamic panel codes. The oblique wing is studied at two skew angles, and in particular, the capability to calculate 3-D thickness effects on the aerodynamic properties of the wing is investigated. The ability to model asymmetric wings in both subsonic and supersonic Mach numbers is shown. The aerodynamic influence coefficient matrix computed by the external programs is inserted in MSC/NASTRAN static aeroelasticity analysis run stream to compute the aeroelastic deformation and internal forces. Various aerodynamic coefficients of the oblique wing were computed for two Mach numbers, 0.7 and 1.4, and the angle of attach -5 through 15 deg

    BMP receptor IA is required in the mammalian embryo for endodermal morphogenesis and ectodermal patterning

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    AbstractBMPRIA is a receptor for bone morphogenetic proteins with high affinity for BMP2 and BMP4. Mouse embryos lacking Bmpr1a fail to gastrulate, complicating studies on the requirements for BMP signaling in germ layer development. Recent work shows that BMP4 produced in extraembryonic tissues initiates gastrulation. Here we use a conditional allele of Bmpr1a to remove BMPRIA only in the epiblast, which gives rise to all embryonic tissues. Resulting embryos are mosaics composed primarily of cells homozygous null for Bmpr1a, interspersed with heterozygous cells. Although mesoderm and endoderm do not form in Bmpr1a null embryos, these tissues are present in the mosaics and are populated with mutant cells. Thus, BMPRIA signaling in the epiblast does not restrict cells to or from any of the germ layers. Cells lacking Bmpr1a also contribute to surface ectoderm; however, from the hindbrain forward, little surface ectoderm forms and the forebrain is enlarged and convoluted. Prechordal plate, early definitive endoderm, and anterior visceral endoderm appear to be expanded, likely due to defective morphogenesis. These data suggest that the enlarged forebrain is caused in part by increased exposure of the ectoderm to signaling sources that promote anterior neural fate. Our results reveal critical roles for BMP signaling in endodermal morphogenesis and ectodermal patterning

    14C terrestrial ages of nine Antarctic meteorites using CO and CO2 temperature extractions

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    As a continuation of the work reported in R. P. BEUKENS et al. (Proc. NIPR Symp. Antarct. Meteorites, 1,224,1988), a suite of Yamato and Trans-Antarctic Mountains meteorites have been analyzed for their ^C content, to give an estimate of their terrestrial age. Further information on the samples\u27 terrestrial history may be obtained from analysis of separate carbon species evolved at different temperatures. We report on data obtained from CO and CO_2 separations from a low temperature (500℃ to 900℃) and high temperature (≈1600℃) fraction from each sample. Three Allan Hills meteorites, ALH-77232 (H4), ALH-78112 (L6) and ALH-78130 (L6), give terrestrial ages >29000 years, and probably represent limit ages due to in situ production. Three other Trans-Antarctic meteorites, BTN-78002 (L6), MET-78028 (L6) and RKP-78002 (H4), give finite ^C ages between 15000 and 27000 years. Three Yamato meteorites, Y-8011 (L6), Y-81132 (H5) and Y-82095 (L3), give ages between 16000 and 22000 years. The low temperature components indicate that recent weathering and atmospheric exchange has taken place for at least four (and possibly six) of the meteorites; ALH-78112,ALH-78130 and Y-81132 have low temperature activities that suggest an earlier exposure and weathering

    Effects of l-Arginine and l-nitro-arginine methyl ester on recovery of neonatal lamb hearts after cold ischemia Evidence for an important role of endothelial production of nitric oxide

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    AbstractMyocardial ischemia and reperfusion results in both ventricular and endothelial dysfunction. We have found that the endothelial defect is a reduced vasodilator response to an intraarterial infusion of acetylcholine that is likely due to reduced nitric oxide release, and we have hypothesized that reduced endothelial nitric oxide production contributes to postischemic cardiac dysfunction. However, others report that nitric oxide is deleterious after ischemia. We therefore examined the effects of infusions of l -arginine (3 mmol/L), a precursor of nitric oxide, d-arginine (3 mmol/L), an inactive stereoisomer of l-Arginine, l -nitro-arginine methyl ester (1 mmol/L); a competitive inhibitor of nitric oxide synthase, and l-nitro-arginine methyl ester (1 mmol/L) plus l-Arginine (3 mmol/L) versus controls in isolated blood-perfused neonatal lamb hearts having 2 hours of cold cardioplegic ischemia. l -nitro-arginine methyl ester was given before reperfusion, and l -arginine and d-arginine were infused for the first 20 minutes of postischemic reperfusion. At 30 minutes of reperfusion, by comparison with the control group, the l -arginine group showed significantly better recovery ( p < 0.05) of left ventricular systolic function (maximum developed pressure, developed pressure at V10 [balloon volume to produce an end-diastolic pressure of 10 mm Hg during baseline measurement], positive maximum dP/dt, and dP/dt at V10), diastolic function (negative maximum dP/dt), coronary blood flow, and endothelial function assessed by the coronary vascular resistance response to acetylcholine. The l -nitro-arginine methyl ester hearts showed a significantly poorer recovery ( p < 0.05) in left ventricular function, coronary blood flow, and endothelial function than the control group. These effects of l -nitro-arginine methyl ester were reversed to equal control values by adding a 3 mmol/L concentration of l -arginine to l -nitro-arginine methyl ester. There were no significant differences in the recovery of any variables between the d-arginine and control groups. These results point to an important salutary role for the endothelial production of nitric oxide in cardiac recovery after hypothermic ischemia in neonatal lamb hearts. The mechanism of these beneficial effects of l -arginine after ischemia and reperfusion is likely due to enhancement of the endothelial production of nitric oxide. (J T horac C ardiovasc S urg 1995;109:81-7

    HLA-Associated viral mutations are common in human immunodeficiency virus type 1 elite controllers

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    Elite controllers (EC) of human immunodeficiency virus type 1 (HTV-1) maintain viremia below the limit of detection without antiretroviral treatment. Virus-specific cytotoxic CD8+ T lymphocytes are believed to play a crucial role in viral containment, but the degree of immune imprinting and compensatory mutations in EC is unclear. We obtained plasma gag, pol, and nef sequences from HLA-diverse subjects and found that 30 to 40% of the predefined HLA-associated polymorphic sites show evidence of immune selection pressure in EC., compared to approximately 50% of the sites in chronic progressors. These data indicate ongoing viral replication and escape from cytotoxic T lymphocytes are present even in strictly controlled HTV-1 infection

    DNA methylation and gene expression in Mimulus guttatus

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    Background The presence of methyl groups on cytosine nucleotides across an organism’s genome (methylation) is a major regulator of genome stability, crossing over, and gene regulation. The capacity for DNA methylation to be altered by environmental conditions, and potentially passed between generations, makes it a prime candidate for transgenerational epigenetic inheritance. Here we conduct the first analysis of the Mimulus guttatus methylome, with a focus on the relationship between DNA methylation and gene expression. Results We present a whole genome methylome for the inbred line Iron Mountain 62 (IM62). DNA methylation varies across chromosomes, genomic regions, and genes. We develop a model that predicts gene expression based on DNA methylation (R2 = 0.2). Post hoc analysis of this model confirms prior relationships, and identifies novel relationships between methylation and gene expression. Additionally, we find that DNA methylation is significantly depleted near gene transcriptional start sites, which may explain the recently discovered elevated rate of recombination in these same regions. Conclusions The establishment here of a reference methylome will be a useful resource for the continued advancement of M. guttatus as a model system. Using a model-based approach, we demonstrate that methylation patterns are an important predictor of variation in gene expression. This model provides a novel approach for differential methylation analysis that generates distinct and testable hypotheses regarding gene expression

    The Fading of the Mpox Outbreak Among Men Who Have Sex With Men: A Mathematical Modelling Study

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    BACKGROUND: In the Netherlands, the number of mpox cases started declining before mpox vaccination was initiated. Most cases were men who have sex with men (MSM). We investigated whether the decline in mpox could be attributed to infection-induced immunity or behavioural adaptations. METHODS: We developed a transmission model and accounted for possible behavioural adaptations: less casual partners and shorter time until MSM with mpox refrain from sexual contacts. RESULTS: Without behavioural adaptations, the peak in modelled cases matched observations, but the decline was less steep than observed. With behavioural adaptations in the model, we found a decline of 16-18% in numbers of casual partners in June and 13-22% in July 2022. Model results showed a halving of the time before refraining from sex. When mpox vaccination started, 57% of MSM with very high sexual activity in the model had been infected. Model scenarios revealed that the outbreak could have waned by November 2022 even without vaccination. CONCLUSIONS: The limited duration of the mpox outbreak in the Netherlands can be ascribed primarily to infection-induced immunity among MSM with high sexual activity levels. The decline was accelerated by behavioural adaptations. Immunity among those most sexually active is essential to impede mpox resurgence

    A C-terminal Pfs48/45 malaria transmission-blocking vaccine candidate produced in the baculovirus expression system

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    This work is licensed under a Creative Commons Attribution 4.0 International License.The Plasmodium falciparum gametocyte surface protein, Pfs48/45, is a potential target for malaria transmission-blocking vaccines. However, due to its size and complexity, expression of the full-length protein has been difficult, leading to focus on the C-terminal six cysteine domain (6C) with the use of fusion proteins to facilitate expression and folding. In this study, we utilized the baculovirus system to evaluate the expression of three Pfs48/45 proteins including the full-length protein, the 6C domain fragment and the 6C domain mutant to prevent glycosylation. Expression of the recombinant Pfs48/45 proteins was conducted in super Sf9 cells combined with the use of tunicamycin to prevent N-glycosylation. The proteins were then evaluated as immunogens in mice to demonstrate the induction of functionally active polyclonal antibody responses as measured in the standard membrane feeding assay (SMFA). Only the 6C protein was found to exhibit significant transmission-reducing activity. Further characterization of the biologically active 6C protein demonstrated it was homogeneous in terms of size, charge, conformation, absence of glycosylation, and containing proper disulfide bond pairings. This study presents an alternative expression system, without the need of a fusion protein partner, for the Pfs48/45 6C protein fragment including further evaluation as a potential transmission-blocking vaccine candidate
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