155 research outputs found
Reliability-based design optimization using kriging surrogates and subset simulation
The aim of the present paper is to develop a strategy for solving
reliability-based design optimization (RBDO) problems that remains applicable
when the performance models are expensive to evaluate. Starting with the
premise that simulation-based approaches are not affordable for such problems,
and that the most-probable-failure-point-based approaches do not permit to
quantify the error on the estimation of the failure probability, an approach
based on both metamodels and advanced simulation techniques is explored. The
kriging metamodeling technique is chosen in order to surrogate the performance
functions because it allows one to genuinely quantify the surrogate error. The
surrogate error onto the limit-state surfaces is propagated to the failure
probabilities estimates in order to provide an empirical error measure. This
error is then sequentially reduced by means of a population-based adaptive
refinement technique until the kriging surrogates are accurate enough for
reliability analysis. This original refinement strategy makes it possible to
add several observations in the design of experiments at the same time.
Reliability and reliability sensitivity analyses are performed by means of the
subset simulation technique for the sake of numerical efficiency. The adaptive
surrogate-based strategy for reliability estimation is finally involved into a
classical gradient-based optimization algorithm in order to solve the RBDO
problem. The kriging surrogates are built in a so-called augmented reliability
space thus making them reusable from one nested RBDO iteration to the other.
The strategy is compared to other approaches available in the literature on
three academic examples in the field of structural mechanics.Comment: 20 pages, 6 figures, 5 tables. Preprint submitted to Springer-Verla
Reliability-based design optimization of shells with uncertain geometry using adaptive Kriging metamodels
Optimal design under uncertainty has gained much attention in the past ten
years due to the ever increasing need for manufacturers to build robust systems
at the lowest cost. Reliability-based design optimization (RBDO) allows the
analyst to minimize some cost function while ensuring some minimal performances
cast as admissible failure probabilities for a set of performance functions. In
order to address real-world engineering problems in which the performance is
assessed through computational models (e.g., finite element models in
structural mechanics) metamodeling techniques have been developed in the past
decade. This paper introduces adaptive Kriging surrogate models to solve the
RBDO problem. The latter is cast in an augmented space that "sums up" the range
of the design space and the aleatory uncertainty in the design parameters and
the environmental conditions. The surrogate model is used (i) for evaluating
robust estimates of the failure probabilities (and for enhancing the
computational experimental design by adaptive sampling) in order to achieve the
requested accuracy and (ii) for applying a gradient-based optimization
algorithm to get optimal values of the design parameters. The approach is
applied to the optimal design of ring-stiffened cylindrical shells used in
submarine engineering under uncertain geometric imperfections. For this
application the performance of the structure is related to buckling which is
addressed here by means of a finite element solution based on the asymptotic
numerical method
Quantile-based optimization under uncertainties using adaptive Kriging surrogate models
Uncertainties are inherent to real-world systems. Taking them into account is
crucial in industrial design problems and this might be achieved through
reliability-based design optimization (RBDO) techniques. In this paper, we
propose a quantile-based approach to solve RBDO problems. We first transform
the safety constraints usually formulated as admissible probabilities of
failure into constraints on quantiles of the performance criteria. In this
formulation, the quantile level controls the degree of conservatism of the
design. Starting with the premise that industrial applications often involve
high-fidelity and time-consuming computational models, the proposed approach
makes use of Kriging surrogate models (a.k.a. Gaussian process modeling).
Thanks to the Kriging variance (a measure of the local accuracy of the
surrogate), we derive a procedure with two stages of enrichment of the design
of computer experiments (DoE) used to construct the surrogate model. The first
stage globally reduces the Kriging epistemic uncertainty and adds points in the
vicinity of the limit-state surfaces describing the system performance to be
attained. The second stage locally checks, and if necessary, improves the
accuracy of the quantiles estimated along the optimization iterations.
Applications to three analytical examples and to the optimal design of a car
body subsystem (minimal mass under mechanical safety constraints) show the
accuracy and the remarkable efficiency brought by the proposed procedure
Optimisation sous contrainte de fiabilité d une coque imparfaite
National audienceSee http://hal.archives-ouvertes.fr/docs/00/59/27/95/ANNEX/r_S5P52J4K.pd
Dynamic effective mass of granular media
We develop the concept of frequency dependent effective mass, M(omega), of
jammed granular materials which occupy a rigid cavity to a filling fraction of
48%, the remaining volume being air of normal room condition or controlled
humidity. The dominant features of M(omega) provide signatures of the
dissipation of acoustic modes, elasticity and aging effects in the granular
medium. We perform humidity controlled experiments and interpret the data in
terms of a continuum model and a "trap" model of thermally activated capillary
bridges at the contact points. The results suggest that attenuation in the
granular materials is influenced significantly by the kinetics of capillary
condensation between the asperities at the contacts.Comment: 4 pages, 3 figure
B-Cell Activating Factor Secreted by Neutrophils Is a Critical Player in Lung Inflammation to Cigarette Smoke Exposure.
Cigarette smoke (CS) is the major cause of chronic lung injuries, such as chronic obstructive pulmonary disease (COPD). In patients with severe COPD, tertiary lymphoid follicles containing B lymphocytes and B cell-activating factor (BAFF) overexpression are associated with disease severity. In addition, BAFF promotes adaptive immunity in smokers and mice chronically exposed to CS. However, the role of BAFF in the early phase of innate immunity has never been investigated. We acutely exposed C57BL/6J mice to CS and show early BAFF expression in the bronchoalveolar space and lung tissue that correlates to airway neutrophil and macrophage influx. Immunostaining analysis revealed that neutrophils are the major source of BAFF. We confirmed in vitro that neutrophils secrete BAFF in response to cigarette smoke extract (CSE) stimulation. Antibody-mediated neutrophil depletion significantly dampens lung inflammation to CS exposure but only partially decreases BAFF expression in lung tissue and bronchoalveolar space suggesting additional sources of BAFF. Importantly, BAFF deficient mice displayed decreased airway neutrophil recruiting chemokines and neutrophil influx while the addition of exogenous BAFF significantly enhanced this CS-induced neutrophilic inflammation. This demonstrates that BAFF is a key proinflammatory cytokine and that innate immune cells in particular neutrophils, are an unconsidered source of BAFF in early stages of CS-induced innate immunity
TACAN is an essential component of the mechanosensitive ion channel responsible for pain sensing
Mechanotransduction, the conversion of mechanical stimuli into electrical signals, is a fundamental process underlying several physiological functions such as touch and pain sensing, hearing and proprioception. This process is carried out by specialized mechanosensitive ion channels whose identities have been discovered for most functions except pain sensing. Here we report the identification of TACAN (Tmem120A), an essential subunit of the mechanosensitive ion channel responsible for sensing mechanical pain. TACAN is expressed in a subset of nociceptors, and its heterologous expression increases mechanically-evoked currents in cell lines. Purification and reconstitution of TACAN in synthetic lipids generates a functional ion channel. Finally, knocking down TACAN decreases the mechanosensitivity of nociceptors and reduces behavioral responses to mechanical but not to thermal pain stimuli, without affecting the sensitivity to touch stimuli. We propose that TACAN is a pore-forming subunit of the mechanosensitive ion channel responsible for sensing mechanical pain
Akt regulates L-type Ca2+ channel activity by modulating Cavα1 protein stability
The insulin IGF-1–PI3K–Akt signaling pathway has been suggested to improve cardiac inotropism and increase Ca2+ handling through the effects of the protein kinase Akt. However, the underlying molecular mechanisms remain largely unknown. In this study, we provide evidence for an unanticipated regulatory function of Akt controlling L-type Ca2+ channel (LTCC) protein density. The pore-forming channel subunit Cavα1 contains highly conserved PEST sequences (signals for rapid protein degradation), and in-frame deletion of these PEST sequences results in increased Cavα1 protein levels. Our findings show that Akt-dependent phosphorylation of Cavβ2, the LTCC chaperone for Cavα1, antagonizes Cavα1 protein degradation by preventing Cavα1 PEST sequence recognition, leading to increased LTCC density and the consequent modulation of Ca2+ channel function. This novel mechanism by which Akt modulates LTCC stability could profoundly influence cardiac myocyte Ca2+ entry, Ca2+ handling, and contractility
FMRFamide-Like Peptides (FLPs) Enhance Voltage-Gated Calcium Currents to Elicit Muscle Contraction in the Human Parasite Schistosoma mansoni
Schistosomes are amongst the most important and neglected pathogens in the world, and schistosomiasis control relies almost exclusively on a single drug. The neuromuscular system of schistosomes is fertile ground for therapeutic intervention, yet the details of physiological events involved in neuromuscular function remain largely unknown. Short amidated neuropeptides, FMRFamide-like peptides (FLPs), are distributed abundantly throughout the nervous system of every flatworm examined and they produce potent myoexcitation. Our goal here was to determine the mechanism by which FLPs elicit contractions of schistosome muscle fibers. Contraction studies showed that the FLP Tyr-Ile-Arg-Phe-amide (YIRFamide) contracts the muscle fibers through a mechanism that requires Ca2+ influx through sarcolemmal voltage operated Ca2+ channels (VOCCs), as the contractions are inhibited by classical VOCC blockers nicardipine, verapamil and methoxyverapamil. Whole-cell patch-clamp experiments revealed that inward currents through VOCCs are significantly and reversibly enhanced by the application of 1 µM YIRFamide; the sustained inward currents were increased to 190% of controls and the peak currents were increased to 180%. In order to examine the biochemical link between the FLP receptor and the VOCCs, PKC inhibitors calphostin C, RO 31–8220 and chelerythrine were tested and all produced concentration dependent block of the contractions elicited by 1 µM YIRFamide. Taken together, the data show that FLPs elicit contractions by enhancing Ca2+ influx through VOCC currents using a PKC-dependent pathway
Retrieval of Context-Associated Memory is Dependent on the Cav3.2 T-Type Calcium Channel
Among all voltage-gated calcium channels, the T-type Ca2+ channels encoded by the Cav3.2 genes are highly expressed in the hippocampus, which is associated with contextual, temporal and spatial learning and memory. However, the specific involvement of the Cav3.2 T-type Ca2+ channel in these hippocampus-dependent types of learning and memory remains unclear. To investigate the functional role of this channel in learning and memory, we subjected Cav3.2 homozygous and heterozygous knockout mice and their wild-type littermates to hippocampus-dependent behavioral tasks, including trace fear conditioning, the Morris water-maze and passive avoidance. The Cav3.2 −/− mice performed normally in the Morris water-maze and auditory trace fear conditioning tasks but were impaired in the context-cued trace fear conditioning, step-down and step-through passive avoidance tasks. Furthermore, long-term potentiation (LTP) could be induced for 180 minutes in hippocampal slices of WTs and Cav3.2 +/− mice, whereas LTP persisted for only 120 minutes in Cav3.2 −/− mice. To determine whether the hippocampal formation is responsible for the impaired behavioral phenotypes, we next performed experiments to knock down local function of the Cav3.2 T-type Ca2+ channel in the hippocampus. Wild-type mice infused with mibefradil, a T-type channel blocker, exhibited similar behaviors as homozygous knockouts. Taken together, our results demonstrate that retrieval of context-associated memory is dependent on the Cav3.2 T-type Ca2+ channel
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