31 research outputs found

    Reducing Uncertainties in a Wind-Tunnel Experiment using Bayesian Updating

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    We perform a fully stochastic analysis of an experiment in aerodynamics. Given estimated uncertainties on the principle input parameters of the experiment, including uncertainties on the shape of the model, we apply uncertainty propagation methods to a suitable CFD model of the experimental setup. Thereby we predict the stochastic response of the measurements due to the experimental uncertainties. To reduce the variance of these uncertainties a Bayesian updating technique is employed in which the uncertain parameters are treated as calibration parameters, with priors taken as the original uncertainty estimates. Imprecise measurements of aerodynamic forces are used as observational data. Motivation and a concrete application come from a wind-tunnel experiment whose parameters and model geometry have substantial uncertainty. In this case the uncertainty was a consequence of a poorly constructed model in the pre-measurement phase. These methodological uncertainties lead to substantial uncertainties in the measurement of forces. Imprecise geometry measurements from multiple sources are used to create an improved stochastic model of the geometry. Calibration against lift and moment data then gives us estimates of the remaining parameters. The effectiveness of the procedure is demonstrated by prediction of drag with uncertainty

    The Application of the Probabilistic Collocation Method to a Transonic Axial Flow Compressor

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    In this paper the Probabilistic Collocation method is used for uncertainty quantification of operational uncertainties in a transonic axial flow compressor (i.e. NASA Rotor 37). Compressor rotors are components of a gas turbine that are highly sensitive to operational and geometrical uncertainties. Validation of the Probabilistic Collocation method with a Monte Carlo simulation using 10,000 Latin Hypercube samples demonstrated that the Probabilistic Collocation method can successfully be applied to a turbomachinery case. The flow through the rotor is characterized by a bow shock in front of the leading edge, which interacts with the boundary layer of the next blade. The total pressure profile at the inlet of the rotor is assumed to be uncertain. A symmetric beta distribution was used for the pressure profile, with the standard deviation such that the uncertainty is in the same order of the measurement accuracy reported in literature. The mass flow was shown to be the most sensitive to the uncertainty, while the efficiency is least affected. It was shown by the compressor maps that is important to take the uncertainty in the total pressure profile at the inlet into account. The standard deviation of the static pressure field showed that the largest variation is present near the shock wave and mainly in the region of the strongest shock, which is near the tip of the blade.Aerospace Engineerin

    Selective Binding of Heparin/Heparan Sulfate Oligosaccharides to Factor H and Factor H-Related Proteins: Therapeutic Potential for C3 Glomerulopathies

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    Complement dysregulation is characteristic of the renal diseases atypical hemolytic uremic syndrome (aHUS) and complement component 3 glomerulopathy (C3G). Complement regulatory protein Factor H (FH) inhibits complement activity, whereas FH-related proteins (FHRs) lack a complement regulatory domain. FH and FHRs compete for binding to host cell glycans, in particular heparan sulfates (HS). HS is a glycosaminoglycan with an immense structural variability, where distinct sulfation patterns mediate specific binding of proteins. Mutations in FH, FHRs, or an altered glomerular HS structure may disturb the FH : FHRs balance on glomerular endothelial cells, thereby leading to complement activation and the subsequent development of aHUS/C3G. In this study, we aimed to identify specific HS structures that could specifically compete off FHRs from HS glycocalyx (HSGlx), without interfering with FH binding. FH/FHR binding to human conditionally immortalized glomerular endothelial cells (ciGEnCs) and HSGlx purified from ciGEnC glycocalyx was assessed. HS modifications important for FH/FHR binding to HSGlx were analyzed using selectively desulfated heparins in competition with purified HSGlx. We further assessed effects of heparinoids on FHR1- and FHR5-mediated C3b deposition on ciGEnCs. In the presence of C3b, binding of FH, FHR1 and FHR5 to ciGEnCs was significantly increased, whereas binding of FHR2 was minimal. FHR1 and 5 competitively inhibited FH binding to HSGlx, leading to alternative pathway dysregulation. FHR1 and FHR5 binding was primarily mediated by N-sulfation while FH binding depended on N-, 2-O- and 6-O-sulfation. Addition of 2-O-desulfated heparin significantly reduced FHR1- and FHR5-mediated C3b deposition on ciGEnCs. We identify 2-O-desulfated heparin derivatives as potential therapeutics for C3G and other diseases with dysregulated complement.Nephrolog
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