Reducing Uncertainties in a Wind-Tunnel Experiment using Bayesian Updating

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

Multiobjective Design Optimization using Nash Games

International audienceIn the area of pure numerical simulation of multidisciplinary coupled systems, the computational cost to evaluate a configuration may be very high. A fortiori, in multi- disciplinary optimization, one is led to evaluate a number of different configurations to iterate on the design parameters. This observation motivates the search for the most in- novative and computationally efficient approaches in all the sectors of the computational chain : at the level of the solvers (using a hierarchy of physical models), the meshes and geometrical parameterizations for shape, or shape deformation, the implementation (on a sequential or parallel architecture; grid computing), and the optimizers (deterministic or semi-stochastic, or hybrid; synchronous, or asynchronous). In the present approach, we concentrate on situations typically involving a small number of disciplines assumed to be strongly antagonistic, and a relatively moderate number of related objective functions. However, our objective functions are functionals, that is, PDE-constrained, and thus costly to evaluate. The aerodynamic and structural optimization of an aircraft configuration is a prototype of such a context, when these disciplines have been reduced to a few major objectives. This is the case when, implicitly, many subsystems are taken into account by local optimizations. Our developments are focused on the question of approximating the Pareto set in cases of strongly-conflicting disciplines. For this purpose, a general computational technique is proposed, guided by a form of sensitivity analysis, with the additional objective to be more economical than standard evolutionary approaches

A “Crossomics” Study Analysing Variability of Different Components in Peripheral Blood of Healthy Caucasoid Individuals

Background: Different immunotherapy approaches for the treatment of cancer and autoimmune diseases are being developed and tested in clinical studies worldwide. Their resulting complex experimental data should be properly evaluated, therefore reliable normal healthy control baseline values are indispensable. Methodology/Principal Findings: To assess intra- and inter-individual variability of various biomarkers, peripheral blood of 16 age and gender equilibrated healthy volunteers was sampled on 3 different days within a period of one month. Complex "crossomics'' analyses of plasma metabolite profiles, antibody concentrations and lymphocyte subset counts as well as whole genome expression profiling in CD4(+)T and NK cells were performed. Some of the observed age, gender and BMI dependences are in agreement with the existing knowledge, like negative correlation between sex hormone levels and age or BMI related increase in lipids and soluble sugars. Thus we can assume that the distribution of all 39.743 analysed markers is well representing the normal Caucasoid population. All lymphocyte subsets, 20% of metabolites and less than 10% of genes, were identified as highly variable in our dataset. Conclusions/Significance: Our study shows that the intra- individual variability was at least two-fold lower compared to the inter-individual one at all investigated levels, showing the importance of personalised medicine approach from yet another perspective

Mitochondrial dysfunction and biogenesis: do ICU patients die from mitochondrial failure?

Mitochondrial functions include production of energy, activation of programmed cell death, and a number of cell specific tasks, e.g., cell signaling, control of Ca2+ metabolism, and synthesis of a number of important biomolecules. As proper mitochondrial function is critical for normal performance and survival of cells, mitochondrial dysfunction often leads to pathological conditions resulting in various human diseases. Recently mitochondrial dysfunction has been linked to multiple organ failure (MOF) often leading to the death of critical care patients. However, there are two main reasons why this insight did not generate an adequate resonance in clinical settings. First, most data regarding mitochondrial dysfunction in organs susceptible to failure in critical care diseases (liver, kidney, heart, lung, intestine, brain) were collected using animal models. Second, there is no clear therapeutic strategy how acquired mitochondrial dysfunction can be improved. Only the benefit of such therapies will confirm the critical role of mitochondrial dysfunction in clinical settings. Here we summarized data on mitochondrial dysfunction obtained in diverse experimental systems, which are related to conditions seen in intensive care unit (ICU) patients. Particular attention is given to mechanisms that cause cell death and organ dysfunction and to prospective therapeutic strategies, directed to recover mitochondrial function. Collectively the data discussed in this review suggest that appropriate diagnosis and specific treatment of mitochondrial dysfunction in ICU patients may significantly improve the clinical outcome

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference