Esteatosis de origen dietético: ¿La inflamación y la Oxidación actúan de forma coordinada? La respuesta metabólica hepática frente a dietas ricas en grasa y colesterol difiere en los ratones con diferentes trastornos metabólicos y carga genética (ApoE-/- y LDLr-/-). Unos responden desarrollando esteatohepatitis y aumentando la expresión de genes relacionados con la inflamación y la oxidación mientras que en otros disminuye la expresión de genes que protegen el desarrollo de esteatosis y obesidad. En humanos, también se aprecian diferencias respecto al desarrollo de esteatosis o esteatohepatitis lo que sugiere que los datos encontrados pueden resultar útiles. Hemos probado la hipótesis de que las moléculas encargadas de la protección frente a la oxidación (principalmente paraoxonasas) actúan de forma coordinada con las quimiocinas responsables del reclutamiento de los macrófagos (proteínas que atraen los monocitos). Presentamos datos que indican que ambas moléculas se expresan constitutivamente en casi todos los tejidos de ratón C57BL/6J. La sorprendente ubicuidad de ambas moléculas y la expresión aparentemente conjunta en las mismas células sugieren que, al menos en el hígado, las respuestas frente a la oxidación y la inflamación pueden estar coordinadas para determinar el curso futuro de las lesiones producidas por el exceso de nutrientes. / Diet-induced hepatic steatosis: Do inflammation and oxidation act coordinately?The metabolic response to high-fat, high-cholesterol diet may differ in mice with different genetic and metabolic background (ApoE-/- and LDLr-/-). Some develop steatohepatitis and increased expression of genes related to both inflammation and oxidation; in others, the expression of genes protective for the development of obesity and steatosis is decreased. Similar differences have been found in humans and consequently obtained data should be considered in translational research. We tested the hypothesis that molecules preventing oxidation (mainly paraoxonases) may coordinately act with responsible effectors for macrophage recruitment (especially monocyte chemoattractant proteins). We present here data indicating that both molecules are constitutively expressed in most tissues from C57BL/6J mice. Surprisingly this ubiquity and the apparent co-expression suggest, at least in liver, that antioxidand and pro-inflammatory responses may jointly determine the course of lesions induced by nutrient excess.

The mechanism of allosteric coupling between the external ligand-binding domain and the internal signaling domain of bacterial chemoreceptors is poorly understood. Genetic, biochemical, and biophysical evidence suggests that transmembrane helix 2 (TM2) undergoes a piston-like displacement of approximately 1-3 Angstroms toward the cytoplasm upon the binding of aspartate to the Tar receptor. The signal is then transmitted to the cytoplasmic signaling domain via the HAMP domain, a conserved motif found in all methyl-accepting chemotaxis proteins (MCPs) and most histidine protein kinases (HPKs). HAMP forms a parallel four-helix bundle consisting of a dimer of two amphipathic helices (AS1 and AS2) connected by a flexible linker. The MLLT sequence between residues Arg-214, at the end of TM2, and the conserved residue Pro-219, at the beginning of AS1 of the HAMP domain (the TM2-HAMP junction), is predicted to be able to form a helical extension of TM2. We hypothesized that perturbing the native secondary structure and/or the length of the TM2-HAMP junction would disrupt the ability of HAMP to communicate the input signal from TM2 to the kinase-control domain. To test this hypothesis, we designed two experiments. First, constructs were made in which 1 to 3 Gly residues were inserted between T218 and P219. Second, Tar variants were constructed in which 1 to 9 Gly residues were inserted between R214 and P219. The results suggest that increasing the length and flexibility of the TM2-HAMP connection tends to uncouple signal propagation between the TM2 and the HAMP elements and suggests that HAMP alone causes an inhibitory effect on the cytoplasmic signaling domain. To determine whether the predicted helical register of the MLLT sequence is an important component of the propagation of the transmembrane signal from TM2 to the HAMP domain, we added and subtracted helical residues to the MLLT sequence. The results suggest that helical register and length of the TM2-HAMP junction are essential for optimal receptor function.

La vérification à l'exécution est une technique prometteuse pour améliorer la sûreté des systèmes complexes. Ces systèmes peuvent être instrumentés afin qu'ils produisent des traces d'exécution permettant d'observer leur utilisation dans des conditions réelles. Un défi important est de fournir aux ingénieurs logiciel un langage formel simple adapté à l'expression des exigences les plus importantes. Dans cette thèse, nous nous intéressons à la vérification de dispositifs médicaux. Nous avons effectué l'analyse approfondie d'un dispositif médical utilisé mondialement afin d'identifier les exigences les plus importantes, ainsi que la nature précise des traces d'exécution qu'il produit. À partir de cette analyse, nous proposons ParTraP, un langage défini formellement et dédié à la spécification de propriétés sur des traces finies. Il a été conçu pour être accessible à des ingénieurs logiciels non qualifiés en méthodes formelles grâce à sa simplicité et son style déclaratif. Le langage étend les patrons de spécification initialement proposé par Dwyer et. al. avec des opérateurs paramétriques et temps-réel, des portées emboîtable, et des quantificateurs de premier ordre. Nous proposons également une technique de mesure de couverture pour ParTraP, et que le niveau de couverture d'une propriété temporelle permet de mieux la comprendre, ainsi que le jeu de traces sur lequel elle est évaluée. Finalement, nous décrivons l'implémentation d'un environnement de développement intégré pour ParTraP, qui est disponible sous une licence libre. / Runtime verification is a promising technique to improve the safety of complex systems. These systems can be instrumented to produce execution traces enabling us to observe their usage in the field. A significant challenge is to provide software engineers with a simple formal language adapted to the expression of their most important requirements. In this thesis, we focus on the verification of medical devices. We performed a thorough analysis of a worldwide-used medical device in order to identify those requirements, as well as the precise nature of its execution traces. In the light of this study, we propose ParTraP, a formally defined language dedicated to property specification for finite traces. It is designed to be accessible to software engineers with no training in formal methods thanks to its simplicity and declarative style. The language extends the specification patterns originally proposed by Dwyer et al. with parametrized constructs, nested scopes, real-time and first-order quantification. We also propose a coverage measurement technique for ParTraP, and we show that coverage information provides insights on a corpus of traces as well as a deeper understanding of temporal properties. Finally, we describe the implementation of an Integrated Development Environment for ParTraP, which is available under a free and open-source license.

The Magellanic Clouds (MCs) consist of a pair of galaxies, the Large Magellanic Cloud (LMC) and the Small Magellanic Cloud (SMC), which are located at a distance of 50 kpc and 60 kpc, with stellar masses of 1010 M and 109 M , respectively. Morphologically they are categorized as irregular type galaxies. The MCs are gas rich and metal poor (Z=0.008 for LMC, and 0.004 for SMC) as compared to the Milky Way (MW), and have active star-forming regions. Their proximity and location at high galactic latitude enable us to resolve their individual populations as well as detect faint stellar populations. It is well known that the MCs are interacting with each other, as well as with the MW. The interaction is supported by the presence of the Magellanic Bridge and the Magellanic Stream. The evolved stellar populations in the MCs help us to understand their evolution and interaction process. The MCs host both Population I as well as Population II stars. This extended range of star formation is a valuable source of information to understand the formation and evolution of galaxies in general, and the MCs in particular. Evolved stellar popu-lation means the stars that have evolved o the main sequence and the giants, such as red giants (RGs), red clump stars, and asymptotic giant branch stars. There is a dominant population of evolved stars present in the MCs, in star clusters as well as in the eld. The aim of the thesis is to study the evolved stellar populations for one of the component of the MCs, the LMC. The study is primarily divided into two parts. (1) Study of sparse star clusters in the LMC: To increase our understanding of sparse star clusters in the LMC, with well estimated parameters, using deep Washington photometric data for 45 LMC clusters. (2) To estimate a metallicity map of LMC: In order to understand the metallicity variation across the galaxy. This is done by creating a high spatial resolution metallicity map of the LMC, using red giant branch (RGB) stars, with the help of photometric data and calibrated using spectroscopic studies of RGs in eld and star clusters. The introduction to the thesis study along with the aim are described in Chapter 1 of the thesis. The three sets of photometric data used for this study are described in Chapter 2. The data sets are: CT1 Washington photometric data for 45 star clusters within the LMC, the VI photometric data from the Optical Gravitational Lensing Experiment Phase-III survey (OGLE III), and the Magellanic Cloud Photometric Survey (MCPS). Study of sparse star clusters in the LMC: A systematic study is per-formed to analyse the 45 cluster candidates, to estimate their parameters (radius, reddening, and age) using the main-sequence turn-o (MSTO), as well as the evolved portion of the colour{magnitude diagram (CMD). The basic parameters were estimated for 33 genuine clusters, whereas the other 12 cluster candidates have been classi ed as possible clusters/asterisms. The study of 33 star clusters are presented in Chapter 3. These clus-ters are categorized as genuine star clusters based on their strong density enhancement and cluster features with respect to their surrounding eld regions. Out of the 33 clusters, 23 are identi ed as single clusters and 10 are found to be members of double clusters. Detailed discussions of all the individual clusters are presented. The estimated parameters for the single and double clusters are listed in two di erent tables. About 50% of the clusters are in the age range 100{300 Myr, the rest of them being older or younger. Comparison with previous age estimates shows some agreement as well as some deviation. The remaining 12 clusters which could not be categorized as genuine star clusters are studied in Chapter 4. These clusters have poor (/suspi-cious) density enhancement and cluster features when compared to their surrounding elds. It is important to study such cluster candidates, as these objects probe the lower limit of the cluster mass function. Detailed discussion on these individual objects are presented and their estimated parameters are tabulated in this chapter. A detailed discussion based on the study of all the 45 inconspicuous clusters is presented in this chapter, including the estimated sizes (radii 2{10 pc), reddening with respect to eld, and location in the LMC. The mass limit estimated for genuine clusters is found to be 1000 M , whereas for possible clusters/asterisms it is few 100 M , using synthetic CMDs. The study of sparse clusters enlarged the number of objects con rmed as genuine star clusters (33) and estimated their fundamental parameters. The study emphasizes that the sizes and masses of the studied sample are found to be similar to that of open clusters in the MW. Thus, this study adds to the lower end of cluster mass distribution in the LMC, suggesting that the LMC, apart from hosting rich clusters, also has formed small, less massive open clusters in the 100{300 Myr age range. The 12 cases of possible clusters/asterisms are worthy of attention, in the sense that they can throw light on the survival time of such objects in the LMC. Photometric metallicity map of the LMC using RGB stars: A metallic-ity map of the LMC is estimated using OGLE III and MCPS photometric data. This is a rst of its kind map of metallicity up to a radius of 4{5 de-grees, derived using photometric data and calibrated using spectroscopic data of RGB stars. The RGB is identi ed in the V, (V I) CMDs of small areal subregions of varying sizes in both data sets. The slope of the RGB is used as an indicator of the average metallicity of a subregion, and this RGB slope is calibrated to metallicity using spectroscopic data for eld and cluster RGs in selected subregions. The metallicity map estimated using OGLE III photometric data is presented in Chapter 5. A method to identify the RGB of small subre-gions within the LMC and estimate its slope by using a consistent and automated method was developed. The technique is robust and indepen-dent of reddening and extinction. The details of calibrating the RGB slopes to metallicities, using previous spectroscopic results of RGs in eld and star clusters are presented. The OGLE III metallicity maps are pre sented, based on four cut-o criteria to separate regions with good ts. The OGLE III map has substantial coverage of the bar, the eastern and western LMC, but does not cover the northern and southern regions. The OGLE III metallicity map shows the bar region to be metal rich whereas the eastern and western regions to be relatively metal poor. The mean metallicity is estimated for three di erent regions within the LMC. For the complete LMC the mean [Fe/H] is = 0.39 dex ( [Fe/H] = 0.10); for the bar region it is = 0.35 dex ( [Fe/H] = 0.9); and for the outer LMC it is = 0.46 dex ( [Fe/H] = 0.11). The metallicity histogram for these di erent regions are also estimated. A radial metallicity gradient is estimated in the de-projected plane of the LMC. The metallicity gradient is seen to remain almost constant in the bar region (till a radius of 2.5 kpc) and has a shallow gradient of 0.066 0.006 dex kpc 1 beyond that till 4 kpc. In Chapter 6 the metallicity map based on MCPS photometric data is estimated. The MCPS data covers more of the northern and south-ern LMC (less of eastern and western regions) and is important to be analysed in order to reveal the metallicity trend of the overall disk. The systematic di erences between the lter systems of MCPS and OGLE III are corrected, and the MCPS slopes are then calibrated using the OGLE III slope{metallicity relation. The MCPS metallicity maps are presented, based on four cut-o criteria to separate regions with good ts. The bar region is found to be metal rich as was found using OGLE III data, whereas the northern and southern regions are marginally metal poor. The mean metallicity estimated for the complete LMC is = 0.37 dex ( [Fe/H] = 0.12); and for the outer LMC it is = 0.41 dex ( [Fe/H] = 0.11). The metallicity histogram for these di erent regions are estimated and compared with the OGLE III distribution. The metallicity range of the complete LMC is found to be almost similar for both data sets. The metallicity distribution within the bar has a narrow range as found using both data sets. The slight di erence between mean metallicity of outer LMC for the two data sets is attributed to their coverage. We suggest that the northern and southern regions of the LMC could be marginally more metal rich than the eastern and western regions. The metallicity gradient of the LMC disk, estimated from MCPS data is found to be shallow 0.049 0.002 dex kpc 1 till about 4 kpc. We also constructed a metallicity map of outliers using both OGLE III and MCPS data, and identi ed subregions where the mean metallic-ity di ers from the surrounding areas. We suggest further spectroscopic studies in order to assess their physical significance. The detailed conclusion of the thesis and future work are presented in Chapter 7. From the study of sparse star clusters in the LMC, it is concluded that LMC has open cluster like star cluster systems. It is important to include them to understand the cluster formation history (CFH) and their survival time scale. Presently, our understanding of the CFH is dominated by rich clusters. The bar of the LMC is found to be the most metal rich region, and the LMC metallicity gradient though shallow, resembles the gradient seen in spiral galaxies. The gradient is also similar to that found in our Galaxy. The higher metallicity in the bar region might indicate an active bar in the past.

Le secteur du bâtiment recèle un fort potentiel d’amélioration de l'efficacité énergétique et de réduction de l’empreinte écologique. Dans cette optique, l’enveloppe du bâtiment joue un rôle important pour relever le défi de la transition énergétique. En effet, une bonne conception de l’enveloppe contribue efficacement à réduire la consommation d’énergie tout en réduisant les émissions de CO2 associés. Cela s’accompagne notamment d’une démarche de développement de nouveaux matériaux et principes constructifs. Ce projet de thèse s’inscrit dans ce cadre en proposant un nouveau matériau composite, qui porte sur l’association de deux matériaux innovant : composite textile mortier (TRC) et matériaux à changement de phase (MCPs). L’objectif de cette combinaison est de contribuer au développement d’éléments de façades multifonctionnelles permettant d’allier performances énergétiques, mécaniques et environnementales. Le but de notre étude est de caractériser en premier lieu, les propriétés mécaniques et thermiques de ces composites puis, d’évaluer l’impact des MCPs sur le confort thermique intérieur pour différentes configurations. Pour atteindre ces objectifs, nous avons adopté une démarche expérimentale et numérique multi échelle. Une campagne expérimentale à l’échelle du laboratoire et in-situ a été menée. En parallèle, nous avons développé un modèle numérique de paroi multicouche, couplé à un modèle de bâtiment. Enfin, nous avons exploité ce couplage pour réaliser une optimisation multicritère à base d’algorithmes génétiques. / The building sector has a great potential to improve energy efficiency and reduce the greenhouse gas emissions. Improvements to the building envelope and Innovations in building materials have the potential to achieve sustainability within the built environment. This PhD thesis focuses on the development of multifunctional façade elements in order to optimize the building energy consumption while maintaining an optimal indoor human thermal comfort. The proposed solution consist of using passive storage by means of phase change materials associated with alternative construction materials such as textile reinforced concrete (TRC). The aim of the study is to characterize mechanical and thermal properties of TRC composites and to evaluate the effect of PCMs on indoor thermal comfort. To meet these objectives, experimental devices have been set up for the characterization (at the component scale and in situ) of the mechanical and thermal behaviour of different TRC panels. In parallel, we have developed a numerical model for the prediction of wall temperature profiles. Finally, a multi-objective optimization of the façade elements is carried out using genetic algorithms to determine the better combinations able to combine the energy performance with the mechanical performance.