1,224 research outputs found

    Wind Tunnel Results of the B-52B with the X-43A Stack

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    A low-speed wind-tunnel test was performed with a three-percent-scale model of a booster rocket mated to an X-43A research vehicle, a combination referred to as the Hyper-X launch vehicle. The test was conducted both in free-stream air and in the presence of a partial model of the B-52B airplane. The objectives of the test were to obtain force and moment data to generate structural loads affecting the pylon of the B-52B airplane and to determine the aerodynamic influence of the B-52B airplane on the Hyper-X launch vehicle to evaluate launch separation characteristics. The wind-tunnel test was conducted at a low-speed wind tunnel in Hampton, Virginia. All moments and forces reported are based either on the aerodynamic influence of the B-52B airplane or are for the Hyper-X launch vehicle in free-stream air. Overall, the test showed that the B-52B airplane imparts a strong downwash onto the Hyper-X launch vehicle, reducing the net lift of the Hyper-X launch vehicle. Also, pitching and rolling moments are imparted onto the booster and are a strong function of the launch-drop angle of attack

    Wind-Tunnel Results of the B-52B with the X-43A Stack

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    A low-speed wind-tunnel test was performed with a 3%-scale model of a booster rocket mated to an X-43A research vehicle, a combination referred to as the Hyper-X launch vehicle. The test was conducted both in freestream air and in the presence of a partial model of the B-52B airplane. The objectives of the test were to obtain force and moment data to generate structural loads affecting the pylon of the B-52B airplane and to determine the aerodynamic influence of the B-52B on the Hyper-X launch vehicle for evaluating launch separation characteristics. The windtunnel test was conducted at a low-speed wind tunnel in Hampton, Virginia. All moments and forces reported are based either on the aerodynamic influence of the B-52B airplane or are for the Hyper-X launch vehicle in freestream air. Overall, the test showed that the B-52B airplane imparts a strong downwash onto the Hyper-X launch vehicle, reducing the net lift of the Hyper-X launch vehicle. Pitching and rolling moments are also imparted onto the booster and are a strong function of the launch-drop angle of attack

    Sestrins are evolutionarily conserved mediators of exercise benefits.

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    Exercise is among the most effective interventions for age-associated mobility decline and metabolic dysregulation. Although long-term endurance exercise promotes insulin sensitivity and expands respiratory capacity, genetic components and pathways mediating the metabolic benefits of exercise have remained elusive. Here, we show that Sestrins, a family of evolutionarily conserved exercise-inducible proteins, are critical mediators of exercise benefits. In both fly and mouse models, genetic ablation of Sestrins prevents organisms from acquiring metabolic benefits of exercise and improving their endurance through training. Conversely, Sestrin upregulation mimics both molecular and physiological effects of exercise, suggesting that it could be a major effector of exercise metabolism. Among the various targets modulated by Sestrin in response to exercise, AKT and PGC1α are critical for the Sestrin effects in extending endurance. These results indicate that Sestrin is a key integrating factor that drives the benefits of chronic exercise to metabolism and physical endurance

    Evidence for ultra-fast outflows in radio-quiet AGNs: III - location and energetics

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    Using the results of a previous X-ray photo-ionization modelling of blue-shifted Fe K absorption lines on a sample of 42 local radio-quiet AGNs observed with XMM-Newton, in this letter we estimate the location and energetics of the associated ultra-fast outflows (UFOs). Due to significant uncertainties, we are essentially able to place only lower/upper limits. On average, their location is in the interval ~0.0003-0.03pc (~10^2-10^4 r_s) from the central black hole, consistent with what is expected for accretion disk winds/outflows. The mass outflow rates are constrained between ~0.01-1 M_{\odot} yr^{-1}, corresponding to >5-10% of the accretion rates. The average lower-upper limits on the mechanical power are log\dot{E}_K~42.6-44.6 erg s^{-1}. However, the minimum possible value of the ratio between the mechanical power and bolometric luminosity is constrained to be comparable or higher than the minimum required by simulations of feedback induced by winds/outflows. Therefore, this work demonstrates that UFOs are indeed capable to provide a significant contribution to the AGN cosmological feedback, in agreement with theoretical expectations and the recent observation of interactions between AGN outflows and the interstellar medium in several Seyferts galaxies.Comment: 5 pages, 3 figures, accepted for publication in MNRA

    Piperidinols that show anti-tubercular activity as inhibitors of arylamine N-acetyltransferase: an essential enzyme for mycobacterial survival inside macrophages

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    Latent M. tuberculosis infection presents one of the major obstacles in the global eradication of tuberculosis (TB). Cholesterol plays a critical role in the persistence of M. tuberculosis within the macrophage during latent infection. Catabolism of cholesterol contributes to the pool of propionyl-CoA, a precursor that is incorporated into cell-wall lipids. Arylamine N-acetyltransferase (NAT) is encoded within a gene cluster that is involved in the cholesterol sterol-ring degradation and is essential for intracellular survival. The ability of the NAT from M. tuberculosis (TBNAT) to utilise propionyl-CoA links it to the cholesterol-catabolism pathway. Deleting the nat gene or inhibiting the NAT enzyme prevents intracellular survival and results in depletion of cell-wall lipids. TBNAT has been investigated as a potential target for TB therapies. From a previous high-throughput screen, 3-benzoyl-4-phenyl-1-methylpiperidinol was identified as a selective inhibitor of prokaryotic NAT that exhibited antimycobacterial activity. The compound resulted in time-dependent irreversible inhibition of the NAT activity when tested against NAT from M. marinum (MMNAT). To further evaluate the antimycobacterial activity and the NAT inhibition of this compound, four piperidinol analogues were tested. All five compounds exert potent antimycobacterial activity against M. tuberculosis with MIC values of 2.3-16.9 µM. Treatment of the MMNAT enzyme with this set of inhibitors resulted in an irreversible time-dependent inhibition of NAT activity. Here we investigate the mechanism of NAT inhibition by studying protein-ligand interactions using mass spectrometry in combination with enzyme analysis and structure determination. We propose a covalent mechanism of NAT inhibition that involves the formation of a reactive intermediate and selective cysteine residue modification. These piperidinols present a unique class of antimycobacterial compounds that have a novel mode of action different from known anti-tubercular drugs

    Curriculum design for inquiry: Preservice elementary teachers' mobilization and adaptation of science curriculum materials

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    Curriculum materials are crucial tools with which teachers engage students in science as inquiry. In order to use curriculum materials effectively, however, teachers must develop a robust capacity for pedagogical design, or the ability to mobilize a variety of personal and curricular resources to promote student learning. The purpose of this study was to develop a better understanding of the ways in which preservice elementary teachers mobilize and adapt existing science curriculum materials to plan inquiry-oriented science lessons. Using quantitative methods, we investigated preservice teachers' curriculum design decision-making and how their decisions influenced the inquiry orientations of their planned science lessons. Findings indicate that preservice elementary teachers were able to accurately assess how inquiry-based existing curriculum materials are and to adapt them to make them more inquiry-based. However, the inquiry orientations of their planned lessons were in large part determined by how inquiry-oriented curriculum materials they used to plan their lessons were to begin with. These findings have important implications for the design of teacher education experiences that foster preservice elementary teachers' pedagogical design capacities for inquiry, as well as the development of inquiry-based science curriculum materials that support preservice and beginning elementary teachers to engage in effective science teaching practice. © 2009 Wiley Periodicals, Inc. J Res Sci Teach 47:820–839, 2010Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/84401/1/20379_ftp.pd

    The Effects of Disc Winds on the Spectrum and Black Hole Growth Rate of Active Galactic Nuclei

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    Several properties of the standard alpha-disc model for active galactic nuclei (AGN) are not entirely consistent with AGN observations. As well as such discrepencies, observations show evidence for the existence of high mass outflow winds originating from the vicinity of the active black hole (BH). Such winds may originate from various parts of the disc and could change the local accretion rate which should alter the emitted spectral energy distribution (SED) and affect the global disc luminosity and the BH growth rate. The new calculations presented here show the effects of several types of winds on the observed and inferred disc properties. Some wind profiles can have a profound effect on the observed SED and can perhaps explain the poorly understood deviations of AGN spectra from standard disc spectra. We show a factor ~2 possible error in estimating the disc luminosity and larger deviations in estimating L/Ledd. The BH growth rate computed without taking the effects of wind into account may be significantly over-estimated. We also suggest a practical way to use the observed SED in order to make first order corrections to BH growth rate and account for the effects of disc winds.Comment: 12 pages, 7 figures, Accepted for publication to MNRA

    The Phyre2 web portal for protein modeling, prediction and analysis

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    Phyre2 is a suite of tools available on the web to predict and analyze protein structure, function and mutations. The focus of Phyre2 is to provide biologists with a simple and intuitive interface to state-of-the-art protein bioinformatics tools. Phyre2 replaces Phyre, the original version of the server for which we previously published a paper in Nature Protocols. In this updated protocol, we describe Phyre2, which uses advanced remote homology detection methods to build 3D models, predict ligand binding sites and analyze the effect of amino acid variants (e.g., nonsynonymous SNPs (nsSNPs)) for a user's protein sequence. Users are guided through results by a simple interface at a level of detail they determine. This protocol will guide users from submitting a protein sequence to interpreting the secondary and tertiary structure of their models, their domain composition and model quality. A range of additional available tools is described to find a protein structure in a genome, to submit large number of sequences at once and to automatically run weekly searches for proteins that are difficult to model. The server is available at http://www.sbg.bio.ic.ac.uk/phyre2. A typical structure prediction will be returned between 30 min and 2 h after submission

    Sestrins are evolutionarily conserved mediators of exercise benefits

    Get PDF
    Exercise is among the most effective interventions for age-associated mobility decline and metabolic dysregulation. Although long-term endurance exercise promotes insulin sensitivity and expands respiratory capacity, genetic components and pathways mediating the meta- bolic benefits of exercise have remained elusive. Here, we show that Sestrins, a family of evolutionarily conserved exercise-inducible proteins, are critical mediators of exercise ben- efits. In both fly and mouse models, genetic ablation of Sestrins prevents organisms from acquiring metabolic benefits of exercise and improving their endurance through training. Conversely, Sestrin upregulation mimics both molecular and physiological effects of exercise, suggesting that it could be a major effector of exercise metabolism. Among the various targets modulated by Sestrin in response to exercise, AKT and PGC1α are critical for the Sestrin effects in extending endurance. These results indicate that Sestrin is a key integrating factor that drives the benefits of chronic exercise to metabolism and physical endurance
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