848 research outputs found

    Effect of Variation of Chord and Span of Ailerons on Rolling and Yawing Moments in Level Flight

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    This report presents the results of an investigation of the rolling and yawing moments due to ailerons of various chords and spans on two airfoils having the Clark Y and U. S. A. 27 wing sections. Some attention is devoted to a study of the effect of scale on rolling and yawing moments and to the effect of slightly rounding the wing tips. The results apply to level flight with the wing chord set at an angle of attack of +4 degrees and to conditions of zero pitch, zero yaw, and zero roll of the airplane. It is planned later to extend the investigation to other attitudes for monoplane and biplane combinations. The work was conducted in the 10 foot wind tunnel of the Bureau of Standards on models of 60-inch span and 10-inch chord. (author

    On Chiral Symmetry Restoration at Finite Density in Large N_c QCD

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    At large N_c, cold nuclear matter is expected to form a crystal and thus spontaneously break translational symmetry. The description of chiral symmetry breaking and translational symmetry breaking can become intertwined. Here, the focus is on aspects of chiral symmetry breaking and its possible restoration that are by construction independent of the nature of translational symmetry breaking---namely spatial averages of chiral order parameters. A system will be considered to be chirally restored provided all spatially-averaged chiral order parameters are zero. A critical question is whether chiral restoration in this sense is possible for phases in which chiral order parameters are locally non-zero but whose spatial averages all vanish. We show that this is not possible unless all chirally-invariant observables are spatially uniform. This result is first derived for Skyrme-type models, which are based on a nonlinear sigma model and by construction break chiral symmetry on a point-by-point basis. A no-go theorem for chiral restoration (in the average sense) for all models of this type is obtained by showing that in these models there exist chirally symmetric order parameters which cannot be spatially uniform. Next we show that the no-go theorem applies to large N_c QCD in any phase which has a non-zero but spatially varying chiral condensate. The theorem is demonstrated by showing that in a putative chirally-restored phase, the field configuration can be reduced to that of a nonlinear sigma model.Comment: 12 pages, 1 tabl

    Effect of Variation of Chord and Span of Ailerons on Rolling and Yawing Moments at Several Angles of Pitch

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    This report presents the results of an extension to higher angles of attack of the investigation of the rolling and yawing moments due to ailerons of various chords and spans on two airfoils having the Clark Y and U. S. A. 27 wings. The measurements were made at various angles of pitch but at zero angle of roll and yaw, the wing chord being set at an angle of +4 degrees to the fuselage axis. In the case of the Clark Y airfoil the measurements have been extended to a pitch angle of 40 degrees, using ailerons of span equal to 67 per cent of the wing semispan and chord equal to 20 and 30 per cent of the wing chord. The work was conducted on wing models of 60-inch span and 10-inch chord

    Modeling Sitagliptin Effect on Dipeptidyl Peptidase 4 (DPP4) Activity in Adults with Hematological Malignancies After Umbilical Cord Blood (UCB) Hematopoietic Cell Transplant (HCT)

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    Background and Objectives— Dipeptidyl peptidase-4 (DPP4) inhibition is a potential strategy to increase the engraftment rate of hematopoietic stem/progenitor cells. A recent clinical trial using sitagliptin, a DPP4 inhibitor approved for type 2 diabetes mellitus, has shown to be a promising approach in adults with hematological malignancies after umbilical cord blood (UCB) hematopoietic cell transplant (HCT). Based on data from this clinical trial, a semi-mechanistic model was developed to simultaneously describe DPP4 activity after multiple doses of sitagliptin in subjects with hematological malignancies after a single-unit UCB HCT. Methods— The clinical study included 24 patients that received myeloablative conditioning followed by 4 oral sitagliptin 600mg with single-unit UCB HCT. Using a nonlinear mixed effects approach, a semi-mechanistic pharmacokinetic/pharmacodynamic model was developed to describe DPP4 activity from this trial data using NONMEM 7.2. The model was used to drive Monte-Carlo simulations to probe various dosage schedules and the attendant DPP4 response. Results— The disposition of sitagliptin in plasma was best described by a 2-compartment model. The relationship between sitagliptin concentration and DPP4 activity was best described by an indirect response model with a negative feedback loop. Simulations showed that twice a day or three times a day dosage schedules were superior to once daily schedule for maximal DPP4 inhibition at the lowest sitagliptin exposure. Conclusion— This study provides the first pharmacokinetic/pharmacodynamic model of sitagliptin in the context of HCT, and provides a valuable tool for exploration of optimal dosing regimens, critical for improving time to engraftment in patients after UCB HCT

    T cells from patients with Candida sepsis display a suppressive immunophenotype

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    BACKGROUND: Despite appropriate therapy, Candida bloodstream infections are associated with a mortality rate of approximately 40 %. In animal models, impaired immunity due to T cell exhaustion has been implicated in fungal sepsis mortality. The purpose of this study was to determine potential mechanisms of fungal-induced immunosuppression via immunophenotyping of circulating T lymphocytes from patients with microbiologically documented Candida bloodstream infections. METHODS: Patients with blood cultures positive for any Candida species were studied. Non-septic critically ill patients with no evidence of bacterial or fungal infection were controls. T cells were analyzed via flow cytometry for cellular activation and for expression of positive and negative co-stimulatory molecules. Both the percentages of cells expressing particular immunophenotypic markers as well as the geometric mean fluorescence intensity (GMFI), a measure of expression of the number of receptors or ligands per cell, were quantitated. RESULTS: Twenty-seven patients with Candida bloodstream infections and 16 control patients were studied. Compared to control patients, CD8 T cells from patients with Candidemia had evidence of cellular activation as indicated by increased CD69 expression while CD4 T cells had decreased expression of the major positive co-stimulatory molecule CD28. CD4 and CD8 T cells from patients with Candidemia expressed markers typical of T cell exhaustion as indicated by either increased percentages of or increased MFI for programmed cell death 1 (PD-1) or its ligand (PD-L1). CONCLUSIONS: Circulating immune effector cells from patients with Candidemia display an immunophenotype consistent with immunosuppression as evidenced by T cell exhaustion and concomitant downregulation of positive co-stimulatory molecules. These findings may help explain why patients with fungal sepsis have a high mortality despite appropriate antifungal therapy. Development of immunoadjuvants that reverse T cell exhaustion and boost host immunity may offer one way to improve outcome in this highly lethal disorder. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-016-1182-z) contains supplementary material, which is available to authorized users

    High potential for weathering and climate effects of non-vascular vegetation in the Late Ordovician

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    It has been hypothesized that predecessors of today’s bryophytes significantly increased global chemical weathering in the Late Ordovician, thus reducing atmospheric CO2 concentration and contributing to climate cooling and an interval of glaciations. Studies that try to quantify the enhancement of weathering by non-vascular vegetation, however, are usually limited to small areas and low numbers of species, which hampers extrapolating to the global scale and to past climatic conditions. Here we present a spatially explicit modelling approach to simulate global weathering by non-vascular vegetation in the Late Ordovician. We estimate a potential global weathering flux of 2.8 (km3 rock) yr−1, defined here as volume of primary minerals affected by chemical transformation. This is around three times larger than today’s global chemical weathering flux. Moreover, we find that simulated weathering is highly sensitive to atmospheric CO2 concentration. This implies a strong negative feedback between weathering by non-vascular vegetation and Ordovician climate

    Validation of Coevolving Residue Algorithms via Pipeline Sensitivity Analysis: ELSC and OMES and ZNMI, Oh My!

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    Correlated amino acid substitution algorithms attempt to discover groups of residues that co-fluctuate due to either structural or functional constraints. Although these algorithms could inform both ab initio protein folding calculations and evolutionary studies, their utility for these purposes has been hindered by a lack of confidence in their predictions due to hard to control sources of error. To complicate matters further, naive users are confronted with a multitude of methods to choose from, in addition to the mechanics of assembling and pruning a dataset. We first introduce a new pair scoring method, called ZNMI (Z-scored-product Normalized Mutual Information), which drastically improves the performance of mutual information for co-fluctuating residue prediction. Second and more important, we recast the process of finding coevolving residues in proteins as a data-processing pipeline inspired by the medical imaging literature. We construct an ensemble of alignment partitions that can be used in a cross-validation scheme to assess the effects of choices made during the procedure on the resulting predictions. This pipeline sensitivity study gives a measure of reproducibility (how similar are the predictions given perturbations to the pipeline?) and accuracy (are residue pairs with large couplings on average close in tertiary structure?). We choose a handful of published methods, along with ZNMI, and compare their reproducibility and accuracy on three diverse protein families. We find that (i) of the algorithms tested, while none appear to be both highly reproducible and accurate, ZNMI is one of the most accurate by far and (ii) while users should be wary of predictions drawn from a single alignment, considering an ensemble of sub-alignments can help to determine both highly accurate and reproducible couplings. Our cross-validation approach should be of interest both to developers and end users of algorithms that try to detect correlated amino acid substitutions

    A Study of Time-Dependent CP-Violating Asymmetries and Flavor Oscillations in Neutral B Decays at the Upsilon(4S)

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    We present a measurement of time-dependent CP-violating asymmetries in neutral B meson decays collected with the BABAR detector at the PEP-II asymmetric-energy B Factory at the Stanford Linear Accelerator Center. The data sample consists of 29.7 fb1{\rm fb}^{-1} recorded at the Υ(4S)\Upsilon(4S) resonance and 3.9 fb1{\rm fb}^{-1} off-resonance. One of the neutral B mesons, which are produced in pairs at the Υ(4S)\Upsilon(4S), is fully reconstructed in the CP decay modes J/ψKS0J/\psi K^0_S, ψ(2S)KS0\psi(2S) K^0_S, χc1KS0\chi_{c1} K^0_S, J/ψK0J/\psi K^{*0} (K0KS0π0K^{*0}\to K^0_S\pi^0) and J/ψKL0J/\psi K^0_L, or in flavor-eigenstate modes involving D()π/ρ/a1D^{(*)}\pi/\rho/a_1 and J/ψK0J/\psi K^{*0} (K0K+πK^{*0}\to K^+\pi^-). The flavor of the other neutral B meson is tagged at the time of its decay, mainly with the charge of identified leptons and kaons. The proper time elapsed between the decays is determined by measuring the distance between the decay vertices. A maximum-likelihood fit to this flavor eigenstate sample finds Δmd=0.516±0.016(stat)±0.010(syst)ps1\Delta m_d = 0.516\pm 0.016 {\rm (stat)} \pm 0.010 {\rm (syst)} {\rm ps}^{-1}. The value of the asymmetry amplitude sin2β\sin2\beta is determined from a simultaneous maximum-likelihood fit to the time-difference distribution of the flavor-eigenstate sample and about 642 tagged B0B^0 decays in the CP-eigenstate modes. We find sin2β=0.59±0.14(stat)±0.05(syst)\sin2\beta=0.59\pm 0.14 {\rm (stat)} \pm 0.05 {\rm (syst)}, demonstrating that CP violation exists in the neutral B meson system. (abridged)Comment: 58 pages, 35 figures, submitted to Physical Review

    Comparison of quality control methods for automated diffusion tensor imaging analysis pipelines

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    © 2019 Haddad et al. The processing of brain diffusion tensor imaging (DTI) data for large cohort studies requires fully automatic pipelines to perform quality control (QC) and artifact/outlier removal procedures on the raw DTI data prior to calculation of diffusion parameters. In this study, three automatic DTI processing pipelines, each complying with the general ENIGMA framework, were designed by uniquely combining multiple image processing software tools. Different QC procedures based on the RESTORE algorithm, the DTIPrep protocol, and a combination of both methods were compared using simulated ground truth and artifact containing DTI datasets modeling eddy current induced distortions, various levels of motion artifacts, and thermal noise. Variability was also examined in 20 DTI datasets acquired in subjects with vascular cognitive impairment (VCI) from the multi-site Ontario Neurodegenerative Disease Research Initiative (ONDRI). The mean fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were calculated in global brain grey matter (GM) and white matter (WM) regions. For the simulated DTI datasets, the measure used to evaluate the performance of the pipelines was the normalized difference between the mean DTI metrics measured in GM and WM regions and the corresponding ground truth DTI value. The performance of the proposed pipelines was very similar, particularly in FA measurements. However, the pipeline based on the RESTORE algorithm was the most accurate when analyzing the artifact containing DTI datasets. The pipeline that combined the DTIPrep protocol and the RESTORE algorithm produced the lowest standard deviation in FA measurements in normal appearing WM across subjects. We concluded that this pipeline was the most robust and is preferred for automated analysis of multisite brain DTI data
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