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La courbe du chômage ne s'est pas inversée
No full textInternational audienceLes chiffres publiés par la Dares le 27 janvier 2014 confirment que 2013 ne s'est pas terminée avec l'inversion espérée de la courbe de chômage. Au contraire, les indicateurs étudiés ne s'améliorent pas. Le chômage est toujours en hausse et il affecte tous les groupes d'âge et les sexes, à l'exception du taux de chômage des hommes de 1524 ans pour lesquels on observe une réduction au cours des deux premiers trimestres de 2013. La croissance constante du chômage de longue durée est particulièrement inquiétante. Le taux mensuel de sortie du chômage est demeuré très bas et stable autour de 10% en 2013. Ainsi, on peut espérer une stabilisation du chômage pour le début de 2014, mais une inversion significative de la courbe semble improbable à court terme. Les offres d'emploi collectées et satisfaites de Pôle emploi ont constamment diminué depuis janvier 2012, sauf au cours des six derniers mois où la situation s'est légèrement améliorée en termes d'offres collectées ce qui laisse entrevoir une reprise possible si la tendance se confirme. Enfin en 2013, le taux de croissance de l'emploi était en baisse ou stable dans presque tous les secteurs d'activité
Intracellular regulation of cell signaling cascades: how location makes a difference
No full textInternational audienceOrganelles such as endosomes and the Golgi apparatus play a critical role in regulating signal transmission to the nucleus. Recent experiments have shown that appropriate positioning of these organelles within the intracellular space is critical for effective signal regulation. To understand the mechanism behind this observation, we consider a reaction-diffusion model of an intracellular signaling cascade and investigate the effect on the signaling of intracellular regulation in the form of a small release of phosphorylated signaling protein, kinase, and/or phosphatase. Variational analysis is applied to characterize the most effective regions for the localization of this intracellular regulation. The results demonstrate that signals reaching the nucleus are most effectively regulated by localizing the release of phosphorylated substrate protein and kinase near the nucleus. Phosphatase release, on the other hand, is nearly equally effective throughout the intracellular space. The effectiveness of the intracellular regulation is affected strongly by the characteristics of signal propagation through the cascade. For signals that are amplified as they propagate through the cascade, reactions in the upstream levels of the cascade exhibit much larger sensitivities to regulation by release of phosphorylated substrate protein and kinase than downstream reactions. On the other hand, for signals that decay through the cascade, downstream reactions exhibit larger sensitivity than upstream reactions. For regulation by phosphatase release, all reactions within the cascade show large sensitivity for amplified signals but lose this sensitivity for decaying signals. We use the analysis to develop a simple model of endosome-mediated regulation of cell signaling. The results demonstrate that signal regulation by the modeled endosome is most effective when the endosome is positioned in the vicinity of the nucleus. The present findings may explain at least in part why endosomes in many cell types localize near the nucleus
Pairwise Decomposition of an MMGBSA Energy Function for Computational Protein Design
No full textInternational audienceComputational protein design (CPD) aims at predicting new proteins or modifying existing ones. The computational challenge is huge as it requires exploring an enormous sequence and conformation space. The difficulty can be reduced by considering a fixed backbone and a discrete set of sidechain conformations. Another common strategy consists in precalculating a pairwise energy matrix, from which the energy of any sequence/conformation can be quickly obtained. In this work, we examine the pairwise decomposition of protein MMGBSA energy functions from a general theoretical perspective, and an implementation proposed earlier for CPD. It includes a Generalized Born term, whose many-body character is overcome using an effective dielectric environment, and a Surface Area term, for which we present an improved pairwise decomposition. A detailed evaluation of the error introduced by the decomposition on the different energy components is performed. We show that the error remains reasonable, compared to other uncertainties. © 2014 Wiley Periodicals, Inc
Photolysis of estrone generates estrogenic photoproducts with higher activity than the parent compound
No full textInternational audienceIn the present study, we aimed to evaluate the effect of UV-visible irradiation on the estrogenicity of an estrone aqueous solution by using chemical analysis associated with an in vitro bioassay and in silico analysis. An estrone aqueous solution was irradiated with an UV-visible high-pressure mercury lamp. By using the MELN in vitro cellular bioassay, based on the induction of a luciferase reporter gene upon the activation of the estrogen receptor by chemicals, we showed that the estrogenic potency of the solution increased after irradiation. High-performance liquid chromatography fractionation of the photolyzed solution followed by in vitro testing of fractions allowed the quantitation of the estrogenic potency of each fraction. Nine photoproducts were detected and characterized by liquid chromatography-mass spectrometry coupling. The observed estrogenic activity is mediated by mono- and multi-hydroxylated photoproducts; it is influenced by the position of hydroxyl groups on the steroidal skeleton. In addition, a structure-activity analysis of the hydroxylated photoproducts confirmed their ability to act as estrogen receptor ligand
Large Deviations for Non-Markovian Diffusions and a Path-Dependent Eikonal Equation
No full textThis paper provides a large deviation principle for Non-Markovian, Brownian motion driven stochastic differential equations with random coefficients. Similar to Gao \& Liu \cite{GL}, this extends the corresponding results collected in Freidlin \& Wentzell \cite{FreidlinWentzell}. However, we use a different line of argument, adapting the PDE method of Fleming \cite{Fleming} and Evans \& Ishii \cite{EvansIshii} to the path-dependent case, by using backward stochastic differential techniques. Similar to the Markovian case, we obtain a characterization of the action function as the unique bounded solution of a path-dependent version of the Eikonal equation. Finally, we provide an application to the short maturity asymptotics of the implied volatility surface in financial mathematics
Dynamique algébrique des applications rationnelles de surfaces
No full textThis thesis contains three parts. The first one is devoted to the study of the set of periodic points for birational surface maps. We prove that any birational transformation of a smooth projective surface whose degree growth is exponential admits a Zariski-dense set of periodic orbits. In the second part, we prove the dynamical Mordell-Lang conjecture for all polynomial birational transformations of the affine plane defined over a field of characteristic zero. Our approach gives a new proof of this conjecture for polynomial automorphisms of the affine plane. The last part is concerned with a problem in affine geometry that was inspired by the generalization to any polynomial map of the dynamical Mordell-Lang conjecture. Given any finite set S of valuations that are defined on the polynomial ring k[x,y] over an algebraically closed field k, trivial on k, we give a necessary and sufficient condition so that the field of fractions of the intersection of the valuation rings of S with k[x,y] has transcendence degree 2 over k.Cette thèse se se compose de trois parties. La première partie est consacrée à l'étude des points périodiques des applications birationnelles des surfaces projectives. Nous montrons que toute application birationnelle de surface dont la croissance des degrés est exponentielle admet un ensemble de points périodiques Zariski dense. Dans la seconde partie, nous démontrons la conjecture de Mordell-Lang dynamique pour toute application polynomiale birationnelle du plan affine définie sur un corps de caractéristique nulle. Notre approche donne une nouvelle démonstration de cette conjecture pour les automorphismes polynomiaux du plan. Enfin la troisième partie porte sur un problème de géométrie affine inspiré par la généralisation au cas de toutes les applications polynomiales du plan affine de la conjecture de Mordell-Lang dynamique. Etant donné un ensemble fini S de valuations sur l'anneau de polynomes k[x,y] sur un corps algébriquement clos k triviales sur k, nous donnons une condition nécessaire et suffisante pour que le corps des fractions de l'intersection des anneaux de valuations de S avec k[x,y] soit de degré de transcendance 2 sur k
Complexity in control-affine systems
No full textParallel sessionInternational audienceWe will consider affine-control systems, i.e., systems in the form _ q(t) = f0(q(t)) + Xm i=1 ui (t)fi (q(t)) Here, the point q belongs to a smooth manifold M the fi 's are smooth vector fields on M u 2 L1([0;T];Rm) This type of system appears in many applications Mechanical systems Quantum control Microswimmers (Tucsnak, Alouges) Neuro-geometry of vision (Mumfor, Petitot
Model-free control and fault accommodation for an experimental greenhouse
No full textInternational audienceThe greenhouse climate control is important in modern agriculture. It is also rather difficult to design: as a matter of fact writing down a "good" mathematical model, which takes into account strong meteorological disturbances, might be an impossible task. The control is here synthesized via a new "model-free" setting, which yields an "intelligent" proportional feedback controller, the tuning of which is straightforward, and even simpler than the intelligent proportional-integral controller, which was already utilized in a previous publication. Our control strategy is successfully tested via an experimental greenhouse. The comparison with the classic Boolean approach, which is popular among manufacturers, demonstrates the superiority of our viewpoint, which permits moreover an efficient actuator fault accommodation. It might be the first model-free fault-tolerant control, which works satisfactorily in practice
