298 research outputs found

    Dynamic Inlet Distortion Prediction with a Combined Computational Fluid Dynamics and Distortion Synthesis Approach

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    A procedure has been developed for predicting peak dynamic inlet distortion. This procedure combines Computational Fluid Dynamics (CFD) and distortion synthesis analysis to obtain a prediction of peak dynamic distortion intensity and the associated instantaneous total pressure pattern. A prediction of the steady state total pressure pattern at the Aerodynamic Interface Plane is first obtained using an appropriate CFD flow solver. A corresponding inlet turbulence pattern is obtained from the CFD solution via a correlation linking root mean square (RMS) inlet turbulence to a formulation of several CFD parameters representative of flow turbulence intensity. This correlation was derived using flight data obtained from the NASA High Alpha Research Vehicle flight test program and several CFD solutions at conditions matching the flight test data. A distortion synthesis analysis is then performed on the predicted steady state total pressure and RMS turbulence patterns to yield a predicted value of dynamic distortion intensity and the associated instantaneous total pressure pattern

    Estimating Engine Airflow in Gas-Turbine Powered Aircraft with Clean and Distorted Inlet Flows

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    The P404-GF-400 Powered F/A-18A High Alpha Research Vehicle (HARV) was used to examine the impact of inlet-generated total-pressure distortion on estimating levels of engine airflow. Five airflow estimation methods were studied. The Reference Method was a fan corrected airflow to fan corrected speed calibration from an uninstalled engine test. In-flight airflow estimation methods utilized the average, or individual, inlet duct static- to total-pressure ratios, and the average fan-discharge static-pressure to average inlet total-pressure ratio. Correlations were established at low distortion conditions for each method relative to the Reference Method. A range of distorted inlet flow conditions were obtained from -10 deg. to +60 deg. angle of attack and -7 deg. to +11 deg. angle of sideslip. The individual inlet duct pressure ratio correlation resulted in a 2.3 percent airflow spread for all distorted flow levels with a bias error of -0.7 percent. The fan discharge pressure ratio correlation gave results with a 0.6 percent airflow spread with essentially no systematic error. Inlet-generated total-pressure distortion and turbulence had no significant impact on the P404-GE400 engine airflow pumping. Therefore, a speed-flow relationship may provide the best airflow estimate for a specific engine under all flight conditions

    Presence of an anti-viral factor in peritoneal dialysis effluent

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    Presence of an anti-viral factor in peritoneal dialysis effluent. Viral peritonitis is an exceptionally rare occurrence in peritoneal dialysis. In fact, up to now, only one case report has been documented in the literature. In a prospective study, peritoneal dialysis effluent (PDE) was specifically cultured for the following viruses: the herpes group of viruses, including herpes simplex types I (HSV) and II, cytomegalovirus (CMV) and varicella-zoster (V-Z), and the enteroviruses group including coxsackie B-5 (Cox B), echo, enterovirus and polio. Cultures were performed under both basal conditions and in the presence of peritonitis. No viral growth was demonstrated. The possible existence of an anti-viral factor in the PDE was therefore raised. In order to investigate this hypothesis, the PDE of 16 patients undergoing intermittent peritoneal dialysis and of 24 patients on continuous ambulatory peritoneal dialysis were examined for anti-viral activity. The method used was analogous to that employed for testing the anti-viral effect of interferon (IFN). The inhibition of the cytopathic effect (CPE) of various viruses was examined in the following tissue cultures: Vero cells (a line of monkey kidney cells) incubated with HSV, vesicular stomatitis virus (VSV) and Cox B; human kidney cells incubated with parainfluenza 3 (Para-3); human foreskin fibroblasts incubated with CMV, HSV and VSV and L-929 (a line of mouse cells) incubated with VSV. As control, unused Dianeal (Travenol, Ashdod, Israel) 1.5 and 4.25 g/dl, normal saline and 5 g/dl dextrose solutions were tested under the same conditions using VSV on Vero. The PDE was also examined for the presence of specific anti-viral antibodies by microneutralization and ELISA tests. The presence of human IFN (β and γ) was evaluated by radioimmunoassay using anti IFN monoclonal antibodies. Human IFN a was tested by a bioassay using MBDK cells with VSV. PDE from both patients on intermittent peritoneal dialysis and continuous ambulatory peritoneal dialysis inhibited the cytopathic activity of all the viruses tested in the various tissue cultures, except for the mouse line of cells. No such inhibition was seen with the control solutions. Only antibodies to HSV were detected in the PDE and their titer did not correlate with the inhibition of cytopathic effect. Human IFN aα, β and γ were not detected. These studies suggest that PDE contains an anti-viral factor which is not a known IFN or an anti-viral antibody. This factor is active against both RNA and DNA viruses in both human and monkey cell cultures

    PHOTOMETRIC PROPERTIES OF THE INTERACTING BINARY BO MONOCEROTIS: EVIDENCE FOR MAGNETIC ACTIVITY

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    ABSTRACT BO Monocerotis (BO Mon) is a severely neglected short-period (2.23 days) Algol-type eclipsing binary star system undergoing angular momentum variations that are likely due to the evolved secondary star experiencing cycles of magnetic activity. We present the first CCD light curves of BO Mon, which were observed at the Kutztown University Observatory (Kutztown, PA) in 2012 using B, V , and I filters. The analysis presented here is the first of its kind for BO Mon and provides the first physical model of the system's parameters. We also incorporate over 40 yr of published times of minimum light to provide a new ephemeris curve and perform a period study that greatly improves, while differing significantly from, an earlier ephemeris analysis that was done more than 13 yr ago. The observed variations in BO Mon's orbital period supply evidence for mass transfer and magnetic activity and our photometric model affords the basic properties of the system for use in future photometric and spectroscopic studies

    A pilot open label, single dose trial of fenobam in adults with fragile X syndrome

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    ObjectiveA pilot open label, single dose trial of fenobam, an mGluR5 antagonist, was conducted to provide an initial evaluation of safety and pharmacokinetics in adult males and females with fragile X syndrome (FXS).MethodsTwelve subjects, recruited from two fragile X clinics, received a single oral dose of 50-150 mg of fenobam. Blood for pharmacokinetic testing, vital signs and side effect screening was obtained at baseline and numerous time points for 6 h after dosing. Outcome measures included prepulse inhibition (PPI) and a continuous performance test (CPT) obtained before and after dosing to explore the effects of fenobam on core phenotypic measures of sensory gating, attention and inhibition.ResultsThere were no significant adverse reactions to fenobam administration. Pharmacokinetic analysis showed that fenobam concentrations were dose dependent but variable, with mean (SEM) peak values of 39.7 (18.4) ng/ml at 180 min after the 150 mg dose. PPI met a response criterion of an improvement of at least 20% over baseline in 6 of 12 individuals (4/6 males and 2/6 females). The CPT did not display improvement with treatment due to ceiling effects.ConclusionsClinically significant adverse effects were not identified in this study of single dose fenobam across the range of dosages utilised. The positive effects seen in animal models of FXS treated with fenobam or other mGluR5 antagonists, the apparent lack of clinically significant adverse effects, and the potential beneficial clinical effects seen in this pilot trial support further study of the compound in adults with FXS

    Nicotine Promotes Tumor Growth and Metastasis in Mouse Models of Lung Cancer

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    Nicotine is the major addictive component of tobacco smoke. Although nicotine is generally thought to have limited ability to initiate cancer, it can induce cell proliferation and angiogenesis in a variety of systems. These properties might enable nicotine to facilitate the growth of tumors already initiated. Here we show that nicotine significantly promotes the progression and metastasis of tumors in mouse models of lung cancer. This effect was observed when nicotine was administered through intraperitoneal injections, or through over-the-counter transdermal patches.In the present study, Line1 mouse adenocarcinoma cells were implanted subcutaneously into syngenic BALB/c mice. Nicotine administration either by intraperitoneal (i.p.) injection or transdermal patches caused a remarkable increase in the size of implanted Line1 tumors. Once the tumors were surgically removed, nicotine treated mice had a markedly higher tumor recurrence (59.7%) as compared to the vehicle treated mice (19.5%). Nicotine also increased metastasis of dorsally implanted Line1 tumors to the lungs by 9 folds. These studies on transplanted tumors were extended to a mouse model where the tumors were induced by the tobacco carcinogen, NNK. Lung tumors were initiated in A/J mice by i.p. injection of NNK; administration of 1 mg/kg nicotine three times a week led to an increase in the size and the number of tumors formed in the lungs. In addition, nicotine significantly reduced the expression of epithelial markers, E-Cadherin and beta-Catenin as well as the tight junction protein ZO-1; these tumors also showed an increased expression of the alpha(7) nAChR subunit. We believe that exposure to nicotine either by tobacco smoke or nicotine supplements might facilitate increased tumor growth and metastasis.Our earlier results indicated that nicotine could induce invasion and epithelial-mesenchymal transition (EMT) in cultured lung, breast and pancreatic cancer cells. This study demonstrates for the first time that administration of nicotine either by i.p. injection or through over-the-counter dermal patches can promote tumor growth and metastasis in immunocompetent mice. These results suggest that while nicotine has only limited capacity to initiate tumor formation, it can facilitate the progression and metastasis of tumors pre-initiated by tobacco carcinogens

    Emergent Properties of Tumor Microenvironment in a Real-life Model of Multicell Tumor Spheroids

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    Multicellular tumor spheroids are an important {\it in vitro} model of the pre-vascular phase of solid tumors, for sizes well below the diagnostic limit: therefore a biophysical model of spheroids has the ability to shed light on the internal workings and organization of tumors at a critical phase of their development. To this end, we have developed a computer program that integrates the behavior of individual cells and their interactions with other cells and the surrounding environment. It is based on a quantitative description of metabolism, growth, proliferation and death of single tumor cells, and on equations that model biochemical and mechanical cell-cell and cell-environment interactions. The program reproduces existing experimental data on spheroids, and yields unique views of their microenvironment. Simulations show complex internal flows and motions of nutrients, metabolites and cells, that are otherwise unobservable with current experimental techniques, and give novel clues on tumor development and strong hints for future therapies.Comment: 20 pages, 10 figures. Accepted for publication in PLOS One. The published version contains links to a supplementary text and three video file

    Cholesterol Influences Voltage-Gated Calcium Channels and BK-Type Potassium Channels in Auditory Hair Cells

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    The influence of membrane cholesterol content on a variety of ion channel conductances in numerous cell models has been shown, but studies exploring its role in auditory hair cell physiology are scarce. Recent evidence shows that cholesterol depletion affects outer hair cell electromotility and the voltage-gated potassium currents underlying tall hair cell development, but the effects of cholesterol on the major ionic currents governing auditory hair cell excitabilityare unknown. We investigated the effects of a cholesterol-depleting agent (methyl beta cyclodextrin, MβCD) on ion channels necessary for the early stages of sound processing. Large-conductance BK-type potassium channels underlie temporal processing and open in a voltage- and calcium-dependent manner. Voltage-gated calcium channels (VGCCs) are responsible for calcium-dependent exocytosis and synaptic transmission to the auditory nerve. Our results demonstrate that cholesterol depletion reduced peak steady-state calcium-sensitive (BK-type) potassiumcurrent by 50% in chick cochlear hair cells. In contrast, MβCD treatment increased peak inward calcium current (∼30%), ruling out loss of calcium channel expression or function as a cause of reduced calcium-sensitive outward current. Changes in maximal conductance indicated a direct impact of cholesterol on channel number or unitary conductance. Immunoblotting following sucrose-gradient ultracentrifugation revealed BK expression in cholesterol-enriched microdomains. Both direct impacts of cholesterol on channel biophysics, as well as channel localization in the membrane, may contribute to the influence of cholesterol on hair cell physiology. Our results reveal a new role for cholesterol in the regulation of auditory calcium and calcium-activated potassium channels and add to the growing evidence that cholesterol is a key determinant in auditory physiology
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