La formulation de matériaux à conduction mixte protonique-électronique (MIEC-H+) performants constituerait une avancée majeure pour le développent d’applications liées au vecteur hydrogène. En particulier cette classe de matériaux constitue une alternative prometteuse aux membranes métalliques ou poreuses pour les dispositifs dédiés de la séparation de l’hydrogène. L’objectif de ce travail de thèse a ainsi été de développer, de caractériser des matériaux présentant des conductivités suffisantes pour l’application visée, de mettre en forme des membranes et d’évaluer leurs performances.La première approche a consisté développer des matériaux monophasiques par substitution d’oxydes conducteurs protoniques par un élément multivalent, Ba(Ce0.5Zr0.5)0.9-xPrxY0.1O3-δ). Parallèlement, nos travaux ont porté sur des composites céramique-céramique constitués d’une phase à conduction protonique et d’une phase à conduction électronique dans des conditions réductrices, xBaCe0.9Y0.1O3-δ-(1-x)Ce0.9Y0.1O2-δ et xBaZr0.9Y0.1O3-δ-(1-x)CeY0.1O2-δ.Les résultats les plus prometteurs en terme de conductivité (> 100 mS.cm-1 @ 600°C) ont été obtenus avec le composite de composition 20BaZr0.9Y0.1O3-δ-80Ce0.9Y0.1O2-δ qui présente une perméabilité à l’hydrogène (VALEUR) du même ordre de grandeur que les meilleures reportées dans la littérature. / The formulation of high-performance mixed protonic-electronic conductors (MPEC) presents a major advancement for the development of hydrogen-linked application. In particular, this class of materials constitute a promising alternative to the metallic or porous membranes for devices devoted for separation of hydrogen. Thus, objective of this thesis work is to develop, characterize materials presenting sufficient conductivities for the targeted applications, to fabricate the membrane and to evaluate their performances.The first approach consisted of developing single-phase materials by substitution of proton-conducting oxides by a multivalent element, Ba(Ce0.5Zr0.5)0.9-xPrxY0.1O3-δ. In parallel, our works focused on the ceramic-ceramic composites which were consisted of a proton-conducting phase and an electron-conducting phase in reducing conditions, xBaCe0.9Y0.1O3-δ-(1-x)Ce0.9Y0.1O2-δ et xBaZr0.9Y0.1O3-δ-(1-x)CeY0.1O2-δ.The most promising results in terms of conductivity (> 100 mS.cm-1 @ 600°C) was obtained with the composite of composition 20BaZr0.9Y0.1O3-δ-80CeY0.1O2-δ which presented hydrogen permeability in the same order of magnitude as the best values reported in the literature.

Les lymphocytes T CD8+ spécifiques de l'antigène sont impliqués dans la réponse immunitaire adaptative et jouent un rôle essentiel dans la protection de l'hôte contre l'infection par des pathogènes intracellulaires. Cette protection de longue durée dépend de la génération de réponses lymphocytaires T CD8+ mémoires, hautement fonctionnelles en termes de fréquence et de fonctionnalité, après réinfection.Après présentation de l'antigène, une cellule T CD8 naïve subit une forte expansion clonale, générant une population hétérogène de cellules activées qui est dominée, au sommet de l'expansion, par des effecteurs CD8 de courte durée (SLEC). Cette expansion est suivie d'une phase de contraction massive par apoptose. Quelques cellules survivent à cette phase de contraction et finissent par se différencier en cellules mémoire hautement compétentes. Les processus par lesquels et le moment où se différencient les précurseurs de mémoire (MPECs) restent largement inconnus, tout comme les étapes ultérieures de leur maturation en cellules mémoire pleinement fonctionnelles. Les signaux d'aide provenant des cellules T CD4+ sont clairement requis tout au long du processus de maturation des MPEC.Notre équipe a montré que les lymphocytes T CD4+ régulateurs FoxP3+ (Tregs) favorisent la maturation des MPEC en limitant l'exposition à l'IL-2 et en fournissant des signaux inhibiteurs, mais ce n'est probablement qu'une facette de l'aide complexe et multiforme apportée par les cellules T CD4+ au MPEC. Les Tregs agissent sur des MPEC préexistants. Les réponses mémoire B et CD8+ partagent des caractéristiques communes, telles que l'expression du facteur de transcription Bcl-6. Les lymphocytes T CD4+ folliculaires (Tfh) sont les principaux producteurs de la cytokine IL-21. Bien que les mécanismes par lesquels les Tfh induisent l’expression de Bcl-6 dans les cellules B doivent être clarifiés, ils pourraient inclure l’IL-21 et l’interaction CD40-CD40L.Dans ce projet de thèse, nous avons étudié le rôle potentiel des Tfh dans l'initiation de la différenciation mémoire T CD8+, dans des modèles de souris transgéniques permettant une déplétion transitoire et sélective des Tfh, infectées par la bactérie recombinante Listeria monocytogenes-OVA.Nous avons montré que dès 2 jours après l'infection, les MPECs très précoces peuvent être identifiés par l’expression du récepteur de chimiokine CXCR5. Ces précurseurs précoces, qui ont un phénotype effecteur, se développent et migrent temporairement à la jonction des zones T et B, où ils interagissent avec les Tfh puis perdent leur expression CXCR5.Cette interaction avec les Tfh, considérés jusqu'à présent comme des auxiliaires exclusifs des cellules B, est nécessaire pour que les MPECs CD8+ deviennent des cellules mémoire compétentes sensibles à l'IL-21, capables de générer des réponses effectrices secondaires efficaces.Cette étude dévoile les premières étapes cruciales dans la génération de la mémoire CD8+, identifie CXCR5 comme le premier marqueur connu des MPECs CD8+, révèle l’implication fondamentale des Tfh dans le CD4 help et indique une coordination possible, via les Tfh, entre les voies de différentiation mémoire CD8+ et B. Ces résultats peuvent avoir des implications pour la conception du vaccin et de l'immunothérapie. / Antigen-specific CD8 T cells are involved in the adaptive immune response and play a critical role in protecting the host from infection by intracellular pathogens. This long-lasting protection depends on the generation of memory CD8+ T cell responses, which are highly functional in terms of frequency and functionality, after secondary infection.Following antigen activation, a naive CD8 T cell undergoes strong clonal expansion, generating a heterogeneous population of activated cells that is dominated, at the peak of expansion, by short-lived CD8 effectors (SLECs). This expansion is followed by a phase of drastic contraction through massive apoptosis. A few cells survive this contraction phase and eventually become highly competent memory cells. Precisely when and how these memory precursors (MPECs) are generated is largely unknown, and so are the subsequent steps of their maturation into fully functional memory cells. Help signals from CD4+ T cells are clearly required throughout the MPEC maturation process.Our team has previously shown that FoxP3+ regulatory CD4+ T cells (Tregs) favor MPECs maturation by limiting exposure to IL-2 and by providing inhibitory signals, but this is probably only one facet of the complex and multifaceted help provided by CD4+ T cells to MPEC, and Tregs act on pre-existing MPECs.B-cell memory and CD8+ T cell memory share some common features, such as the expression of the transcription factor Bcl-6. Tfh are major producers of the cytokine IL-21. The mechanisms by which Tfh induces Bcl-6 in B-cells need to be clarified, they might include IL-21 and CD40-CD40L.In this PhD project, we have investigated the potential role of Tfh on the initiation of CD8 memory differentiation, in transgenic mice models, allowing transient and selective depletion of Tfh cells, infected by recombinant Listeria monocytogenes-OVA.We have shown that as early as 2 days after infection, very early memory precursors can be identified by their expression of the chemokine receptor CXCR5. These early precursors, which have an effector phenotype, expand and temporarily migrate to the junction of T-cell and B-cell zones, where they interact with follicular CD4 T cells (Tfh) then lose their CXCR5 expression.Remarkably, this interaction with Tfh, hitherto considered as exclusive B-cell helpers, is required for memory precursors to become competent memory cells responsive to IL-21 and capable of mounting efficient cytotoxic secondary effector responses.This study thus unveils critical early steps in the generation of CD8 memory, identifies CXCR5 as the earliest known marker of CD8 memory precursors, reveals a major helper role for Tfh, and points to possible coordination, through Tfh, between the pathways of CD8 and B-cell memory generation. These findings may have implications for vaccine and immunotherapy design.

Orientador: Vera Lúcia Mores Rall / Resumo: A mastite bovina é uma das doenças que mais causam prejuízos às propriedades leiteiras e, apesar dos programas de controle, Escherichia coli destaca-se como importante patógeno ambiental causador desta enfermidade na sua forma clínica. Isolados obtidos de infecções nas mamas são classificadas como E. coli patogênica mamária (MPEC). O objetivo deste estudo foi caracterizar geneticamente isolados de E. coli a partir de leite de vacas com mastite clínica utilizando técnicas moleculares, bem como investigar os padrões de aderência e resistência aos antimicrobianos dos isolados, para isso a investigação dos grupos filogenéticos, genes de virulência, presença de clones (por Pulsed field gel electrophoresis, PFGE), tipos de adesão em células HeLa, resistência aos antimicrobianos e genes relacionados com essa resistência foram realizados em 110 E. coli isoladas de leite de vacas com mastite clínica de diferentes fazendas dos estados de São Paulo, Minas Gerais e Paraná. De acordo com a presença dos genes específicos arpA, chuA, yjaA e TspE4.C2, os isolados foram classificados principalmente nos grupos comensais A (50,9 %) e B1 (38,2 %), seguidos dos grupos D (2,7 %), C (1,8 %) e B2/E/F/Escherichia clade I (0,9 %). Três isolados (2,7 %) não foram categorizados em nenhum desses grupos, classificados como de grupo filogenético desconhecido. Nenhum dos 110 isolados apresentou genes que caracterizam E. coli diarreiogênicas (DEC), entretanto os genes astA e shf, geralmente encontrados em E.... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Bovine mastitis is one of the diseases that most causes damage to dairy properties and, despite control programs, Escherichia coli stands out as an important environmental pathogen that causes this disease in its clinical form. Isolates obtained from breast infections are classified as mammary pathogenic E. coli (MPEC). The objective of this study was to genetically characterize E. coli isolates from milk of cows with clinical mastitis using molecular techniques, as well as to investigate the adhesion patterns and antimicrobial resistance of isolates, for this purpose the investigation of phylogenetic groups, virulence genes, presence of clones (by Pulsed field gel electrophoresis, PFGE), HeLa cell adhesion types, antimicrobial resistance, and genes related to this resistance were performed on 110 E. coli isolated from milk of cows with clinical mastitis from different state farms from São Paulo, Minas Gerais and Paraná. According to the presence of the specific genes arpA, chuA, yjaA and TspE4.C2, isolates were classified mainly in commensal groups A (50.9 %) and B1 (38.2 %), followed by groups D (2.7 %), C (1.8 %) and B2/E/F/Escherichia clade I (0.9 %). Three isolates (2.7 %) were not categorized in any of these groups, classified as unknown phylogenetic group. None of the 110 isolates presented genes that characterize diarrheagenic E. coli (DEC), however, the astA and shf genes, commonly found in enteroaggregative E. coli, were identified in 7.3 % (8/110) and 10.3 % (3/29)... (Complete abstract click electronic access below) / Doutor

Die vorliegende Arbeit beschaeftigt sich mit Gleichgewichtsproblemen unter Gleichgewichtsrestriktionen, sogenannten EPECs (Englisch: Equilibrium Problems with Equilibrium Constraints). Konkret handelt es sich um gekoppelte Zwei-Ebenen-Optimierungsprobleme, bei denen Nash- Gleichgewichte fuer die Entscheidungen der oberen Ebene gesucht sind. Ein Ziel der Arbeit besteht in der Formulierung dualer Stationaritaetsbedingungen zu solchen Problemen. Als Anwendung wird ein oligopolistisches Wettbewerbsmodell fuer Strommaerkte betrachtet. Zur Gewinnung qualitativer Hypothesen ueber die Struktur der betrachteten Modelle (z.B. Inaktivitaet bestimmter Marktteilnehmer) aber auch fuer moegliche numerische Zugaenge ist es wesentlich, EPEC-Loesungen explizit bezueglich der Eingangsdaten des Problems zu formulieren. Der Weg dorthin erfordert eine Strukturanalyse der involvierten Optimierungsprobleme (constraint qualifications, Regularitaet), die Herleitung von Stabilitaetsresultaten bestimmter mengenwertiger Abbildungen und die Nutzung von Transformationsformeln fuer die sogenannte Ko-Ableitung. Weitere Schwerpunkte befassen sich mit der Beziehung zwischen verschiedenen dualen Stationaritaetstypen (S- und M-Stationaritaet) sowie mit stochastischen Erweiterungen der betrachteten Problemklasse, sogenannten SEPECs. / This thesis is concerned with equilibrium problems with equilibrium constraints or EPECs. Concretely, we consider models composed by coupling together two-level optimization problems, the upper-level solutions to which are non-cooperative (Nash-Cournot) equilibria. One of the main goals of the thesis involves the formulation of dual stationarity conditions to EPECs. A model of oligopolistic competition for electricity markets is considered as an application. In order to profit from qualitative hypotheses concerning the structure of the considered models, e.g., inactivity of certain market participants at equilibrium, as well as to provide conditions useful for numerical procedures, the ablilty to formulate EPEC solutions in relation to the input data of the problem is of considerable importance. The way to do this requires a structural analysis of the involved optimization problems, e.g., constraints qualifications, regularity; the derivation of stability results for certain multivalued mappings, and the usage of transformation formulae for so-called coderivatives. Further important topics address the relationship between various dual stationarity types, e.g., S- and M-stationarity, as well as the extension of the considered problem classes to a stochastic setting, i.e., stochastic EPECs or SEPECs.

<p>This thesis investigates the second-best toll pricing and capacity expansion problems when stated as mathematical programs with equilibrium constraints (MPEC). Three main questions are rised: First, whether conventional descent methods give sufficiently good solutions, or whether global solution methods are to prefer. Second, how the performance of the considered solution methods scale with network size. Third, how a discretized stochastic mathematical program with equilibrium constraints (SMPEC) formulation of a stochastic network design problem can be practically solved. An attempt to answer these questions is done through a series ofnumerical experiments.</p><p>The traffic system is modeled using the Wardrop’s principle for user behavior, separable cost functions of BPR- and TU71-type. Also elastic demand is considered for some problem instances.</p><p>Two already developed method approaches are considered: implicit programming and a cutting constraint algorithm. For the implicit programming approach, several methods—both local and global—are applied and for the traffic assignment problem an implementation of the disaggregate simplicial decomposition (DSD) method is used. Regarding the first question concerning local and global methods, our results don’t give a clear answer.</p><p>The results from numerical experiments of both approaches on networks of different sizes shows that the implicit programming approach has potential to solve large-scale problems, while the cutting constraint algorithm scales worse with network size.</p><p>Also for the stochastic extension of the network design problem, the numerical experiments indicate that implicit programming is a good approach to the problem.</p><p>Further, a number of theorems providing sufficient conditions for strong regularity of the traffic assignment solution mapping for OD connectors and BPR cost functions are given.</p>

This thesis investigates the second-best toll pricing and capacity expansion problems when stated as mathematical programs with equilibrium constraints (MPEC). Three main questions are rised: First, whether conventional descent methods give sufficiently good solutions, or whether global solution methods are to prefer. Second, how the performance of the considered solution methods scale with network size. Third, how a discretized stochastic mathematical program with equilibrium constraints (SMPEC) formulation of a stochastic network design problem can be practically solved. An attempt to answer these questions is done through a series ofnumerical experiments. The traffic system is modeled using the Wardrop’s principle for user behavior, separable cost functions of BPR- and TU71-type. Also elastic demand is considered for some problem instances. Two already developed method approaches are considered: implicit programming and a cutting constraint algorithm. For the implicit programming approach, several methods—both local and global—are applied and for the traffic assignment problem an implementation of the disaggregate simplicial decomposition (DSD) method is used. Regarding the first question concerning local and global methods, our results don’t give a clear answer. The results from numerical experiments of both approaches on networks of different sizes shows that the implicit programming approach has potential to solve large-scale problems, while the cutting constraint algorithm scales worse with network size. Also for the stochastic extension of the network design problem, the numerical experiments indicate that implicit programming is a good approach to the problem. Further, a number of theorems providing sufficient conditions for strong regularity of the traffic assignment solution mapping for OD connectors and BPR cost functions are given.

The thesis focuses on a mixed integer linear programming (MILP) formulation for a bi-level mathematical program with equilibrium constraints (MPEC) considering chance constraints. The particular MPEC problem relates to a power producer’s bidding strategy: maximize its total benefit through determining bidding price and bidding power output while considering an electricity pool’s operation and guessing the rival producer’s bidding price. The entire decision-making process can be described by a bi-level optimization problem. The contribution of our thesis is the MILP formulation of this problem considering the use of chance constrained mathematical program for handling the uncertainties. First, the lower-level poor operation problem is replaced by Karush-Kuhn-Tucker (KKT) optimality condition, which is further converted to an MILP formulation except a bilinear item in the objective function. Secondly, duality theory is implemented to replace the bilinear item by linear items. Finally, two types of chance constraints are examined and modeled in MILP formulation. With the MILP formulation, the entire MPEC problem considering randomness in price guessing can be solved using off-shelf MIP solvers, e.g., Gurobi. A few examples and a case study are given to illustrate the formulation and show the case study results.

This dissertation focuses on selected issues in regard to the mathematical modeling of electricity markets. In a first step the interrelations of electric power market modeling are highlighted a crossroad between operations research, applied economics, and engineering. In a second step the development of a large-scale continental European economic engineering model named ELMOD is described and the model is applied to the issue of wind integration. It is concluded that enabling the integration of low-carbon technologies appears feasible for wind energy. In a third step algorithmic work is carried out regarding a game theoretic model. Two approaches in order to solve a discretely-constrained mathematical program with equilibrium constraints using disjunctive constraints are presented. The first one reformulates the problem as a mixed-integer linear program and the second one applies the Benders decomposition technique. Selected numerical results are reported.

This dissertation focuses on selected issues in regard to the mathematical modeling of electricity markets. In a first step the interrelations of electric power market modeling are highlighted a crossroad between operations research, applied economics, and engineering. In a second step the development of a large-scale continental European economic engineering model named ELMOD is described and the model is applied to the issue of wind integration. It is concluded that enabling the integration of low-carbon technologies appears feasible for wind energy. In a third step algorithmic work is carried out regarding a game theoretic model. Two approaches in order to solve a discretely-constrained mathematical program with equilibrium constraints using disjunctive constraints are presented. The first one reformulates the problem as a mixed-integer linear program and the second one applies the Benders decomposition technique. Selected numerical results are reported.