2,489 research outputs found

    Heat Transfer Due to Unsteady Effects as Investigated in a High-Speed, Full-Scale, Fully-Cooled Turbine Vane and Rotor Stage

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    Experiments were conducted to examine the effects of film cooling on a gas turbine engine’s high‐pressure turbine section. The focus for this effort was in the tip/shroud region of a rotor stage and a high pressure turbine vane. A primary goal was to understand the unsteady flow effects. Attempts were also made to characterize the effects as caused by the fully‐cooled rotor stage. Data for this investigation was taken at the U.S. Air Force’s Turbine Research Facility (TRF), a transient blowdown facility with instrumentation fitted to a full‐scale, high‐speed, fully‐cooled vane and rotor stage of proprietary design. Measurements of pressure, temperature, and heat flux were taken at flow conditions non‐dimensionally matched to actual engine operation. From this high speed data the relevant film‐cooling parameters (heat transfer coefficients, film cooling effectiveness, and overall effectiveness) were determined over a range of operating conditions. Of specific interest were the high frequency events associated with the blade passage frequency on both the vane and shroud surfaces. It was found that tip flow and vane wake‐rotor interaction result in noticeable heat flux variations in time

    Bäcklund transformations for noncommutative anti-self-dual Yang-Mills equations

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    We present Bäcklund transformations for the non-commutative anti-self-dual Yang–Mills equations where the gauge group is G = GL(2) and use it to generate a series of exact solutions from a simple seed solution. The solutions generated by this approach are represented in terms of quasi-determinants and belong to a non-commutative version of the Atiyah–Ward ansatz. In the commutative limit, our results coincide with those by Corrigan, Fairlie, Yates and Goddard

    Patterns of Psychotropic Medication at Admission for Youth in Residential Care

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    High levels of psychotropic medication use and polypharmacy are common for emotionally and behaviorally troubled youth entering residential care. Polypharmacy has often been characterized as an especially serious problem in this vulnerable population. Latent Class Analysis was used to identify medication subgroups for 636 youth in an intensive residential program. Additionally, auxiliary analyses (e.g., diagnoses, demographics, expressed problem behaviors) were used to identify the personal and behavioral attributes associated with individuals in each of the latent classes. Three distinct medication patterns emerged: low/no psychotropic medication, the combination of antidepressant and antipsychotic medications, and multiple psychotropic medications. The latent classes were significantly different from one another on 12 of the 14 variables, helping explicate how patient and clinical characteristics underlie patterns of psychotropic medication use. Findings of this study, combined with additional research, hold promise for leading to improved, youth-centered prescribing practices. Our findings also highlight the need for careful monitoring of the types and range of medications that some youth are prescribed, and research on how youth with certain background characteristics are more likely to get prescribed multiple psychotropic medications. For youth experiencing higher levels of psychotropic polypharmacy, medication regimens need thoughtful reassessment using the principle of sufficiency as the foundation for medication management

    A pilot study evaluating concordance between blood-based and patient-matched tumor molecular testing within pancreatic cancer patients participating in the Know Your Tumor (KYT) initiative

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    Recent improvements in next-generation sequencing (NGS) technology have enabled detection of biomarkers in cell-free DNA in blood and may ultimately replace invasive tissue biopsies. However, a better understanding of the performance of blood-based NGS assays is needed prior to routine clinical use. As part of an IRBapproved molecular profiling registry trial of pancreatic ductal adenocarcinoma (PDA) patients, we facilitated blood-based NGS testing of 34 patients from multiple community-based and high-volume academic oncology practices. 23 of these patients also underwent traditional tumor tissue-based NGS testing. cfDNA was not detected in 9/34 (26%) patients. Overall concordance between blood and tumor tissue NGS assays was low, with only 25% sensitivity of blood-based NGS for tumor tissue NGS. Mutations in KRAS, the major PDA oncogene, were only detected in 10/34 (29%) blood samples, compared to 20/23 (87%) tumor tissue biopsies. The presence of mutations in circulating DNA was associated with reduced overall survival (54% in mutation-positive versus 90% in mutation-negative). Our results suggest that in the setting of previously treated, advanced PDA, liquid biopsies are not yet an adequate substitute for tissue biopsies. Further refinement in defining the optimal patient population and timing of blood sampling may improve the value of a blood-based test. © Pishvaian et al

    Aprotinin inhibits proinflammatory activation of endothelial cells by thrombin through the protease-activated receptor 1

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    ObjectiveThrombin is generated in significant quantities during cardiopulmonary bypass and mediates adverse events, such as platelet aggregation and proinflammatory responses, through activation of the high-affinity thrombin receptor protease-activated receptor 1, which is expressed on platelets and endothelium. Thus antagonism of protease-activated receptor 1 might have broad therapeutic significance. Aprotinin, used clinically to reduce transfusion requirements and the inflammatory response to bypass, has been shown to inhibit protease-activated receptor 1 on platelets in vitro and in vivo. Here we have examined whether aprotinin inhibits endothelial protease-activated receptor 1 activation and resulting proinflammatory responses induced by thrombin.MethodsProtease-activated receptor 1 expression and function were examined in cultured human umbilical vein endothelial cells after treatment with α-thrombin at 0.02 to 0.15 U/mL in the presence or absence of aprotinin (200-1600 kallikrein inhibitory units/mL). Protease-activated receptor 1 activation was assessed by using an antibody, SPAN-12, which detects only the unactivated receptor, and thrombin-mediated calcium fluxes. Other thrombin-dependent inflammatory pathways investigated were phosphorylation of the p42/44 mitogen-activated protein kinase, upregulation of the early growth response 1 transcription factor, and production of the proinflammatory cytokine interleukin 6.ResultsPretreatment of cultured endothelial cells with aprotinin significantly spared protease-activated receptor 1 receptor cleavage (P < .0001) and abrogated calcium fluxes caused by thrombin. Aprotinin inhibited intracellular signaling through p42/44 mitogen-activated protein kinase (P < .05) and early growth response 1 transcription factor (P < .05), as well as interleukin 6 secretion caused by thrombin (P < .005).ConclusionsThis study demonstrates that endothelial cell activation by thrombin and downstream inflammatory responses can be inhibited by aprotinin in vitro through blockade of protease-activated receptor 1. Our results provide a new molecular basis to help explain the anti-inflammatory properties of aprotinin reported clinically

    Clinopyroxene diversity and magma plumbing system processes in an accreted Pacific ocean island, Panama

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    Characterising equilibrium and disequilibrium crystal-melt processes is critical in determining the extent of magma mixing and crystallization conditions in the roots of volcanoes. However, these processes remain poorly investigated in most Pacific intraplate ocean settings that are difficult to access and study. To help address this issue, we investigated crystallization conditions of clinopyroxene phenocrysts in an accreted Palaeogene oceanic island in Panama. Petrographic and geochemical observations, petrological modelling of major and trace elements, and liquid-mineral multicomponent equilibrium tests were carried out using basalts, picrites, and hawaiites of the transitional tholeiitic shield to alkaline post-shield volcanic stages of the island. Five types of clinopyroxene crystals were identified, including (1) microphenocrysts with micron-scale oscillatory zoning, (2) primitive, yet resorbed picrite-hosted phenocrysts, (3) chemically homogeneous, anhedral crystals found in the remaining basalts, (4) Ti–rich euhedral hawaiite-hosted phenocrysts, and (5) evolved sector-zoned phenocrysts. Liquid-clinopyroxene multicomponent equilibrium tests in combination with textural analysis show that ~ 74% of the studied clinopyroxenes are in possible major element equilibrium with one of the available whole rock magma compositions, of which only 21% are equilibrated with their carrier liquid. To deconvolute clinopyroxene-melt pairings and determine plumbing system conditions, we combine rhyolite-MELTS modelling, geothermobarometry, and major- and trace-element equilibrium evaluations, limiting crystallization conditions to crustal levels (< 23 km depth). No migration of magmatic reservoirs to deeper levels is observed during the shield- to post-shield transition. These results suggest the occurrence of an extensive crystal mush system during the late shield to post-shield volcanic stages of this intraplate volcanic system, with both primitive and evolved crystallization domains sampled during eruptions

    Recombinant human L-ficolin directly neutralizes hepatitis C virus entry

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    L-ficolin is a soluble pattern recognition molecule expressed by the liver that contributes to innate immune defense against microorganisms. It is well described that binding of L-ficolin to specific pathogen-associated molecular patterns activates the lectin complement pathway, resulting in opsonization and lysis of pathogens. In this study, we demonstrated that in addition to this indirect effect, L-ficolin has a direct neutralizing effect against hepatitis C virus (HCV) entry. Specific, dose-dependent binding of recombinant L-ficolin to HCV glycoproteins E1 and E2 was observed. This interaction was inhibited by soluble L-ficolin ligands. Interaction of L-ficolin with E1 and E2 potently inhibited entry of retroviral pseudoparticles bearing these glycoproteins. L-ficolin also inhibited entry of cell-cultured HCV in a calcium-dependent manner. Neutralizing concentrations of L-ficolin were found to be circulating in the serum of HCV-infected individuals. This is the first description of direct neutralization of HCV entry by a ficolin and highlights a novel role for L-ficolin as a virus entry inhibitor

    CMB observations from the CBI and VSA: A comparison of coincident maps and parameter estimation methods

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    We present coincident observations of the Cosmic Microwave Background (CMB) from the Very Small Array (VSA) and Cosmic Background Imager (CBI) telescopes. The consistency of the full datasets is tested in the map plane and the Fourier plane, prior to the usual compression of CMB data into flat bandpowers. Of the three mosaics observed by each group, two are found to be in excellent agreement. In the third mosaic, there is a 2 sigma discrepancy between the correlation of the data and the level expected from Monte Carlo simulations. This is shown to be consistent with increased phase calibration errors on VSA data during summer observations. We also consider the parameter estimation method of each group. The key difference is the use of the variance window function in place of the bandpower window function, an approximation used by the VSA group. A re-evaluation of the VSA parameter estimates, using bandpower windows, shows that the two methods yield consistent results.Comment: 10 pages, 6 figures. Final version. Accepted for publication in MNRA

    Stochastic combinations of actin regulatory proteins are sufficient to drive filopodia formation.

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    Assemblies of actin and its regulators underlie the dynamic morphology of all eukaryotic cells. To understand how actin regulatory proteins work together to generate actin-rich structures such as filopodia, we analyzed the localization of diverse actin regulators within filopodia in Drosophila embryos and in a complementary in vitro system of filopodia-like structures (FLSs). We found that the composition of the regulatory protein complex where actin is incorporated (the filopodial tip complex) is remarkably heterogeneous both in vivo and in vitro. Our data reveal that different pairs of proteins correlate with each other and with actin bundle length, suggesting the presence of functional subcomplexes. This is consistent with a theoretical framework where three or more redundant subcomplexes join the tip complex stochastically, with any two being sufficient to drive filopodia formation. We provide an explanation for the observed heterogeneity and suggest that a mechanism based on multiple components allows stereotypical filopodial dynamics to arise from diverse upstream signaling pathways.Herchel Smith Fellowship, Funai Foundation scholarship, Austrian Science Fun
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