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Cu(In,Ga)Se2, in short CIGS, solar cells have received considerable attention among photovoltaic solar cells because of their high conversion efficiency, flexibility and lightweight. The challenge in CIGS technology nowadays is not only to enhance performances but also to find low cost processing options. The use of CIGS modules built from monolithic interconnected cells on steel sheets is a promising solution; however it requires an additional dielectric layer interposed between the substrate and the entire active stack. Thus, the focus of this thesis was to elaborate a novel dielectric systems prepared on steel substrates and to optimize molybdenum layers as contacts for the fabrication of “high temperature” flexible CIGS solar cells. Polysilazane hybrid polymers were identified and explored to act as a dielectric layer for CIGS solar cells. Coatings were performed on stainless steel substrates using a straightforward “bar coating” deposition method which is suitable for industrial rolling processes. The problem with polysilazane coatings is that they often suffer from thermal instability and cracking due to the high annealing temperature required for growing the CIGS absorbing layer. Indeed, our thermal analysis reveals an important mass loss of around 25 wt. % for type of polysilazane we use. The mass reduction was assigned to chemical transformations of the polymer evidenced by volatilization of different gases and evolution of solvent. Such degradations show a severe weakening of the dielectric strength of polysilazane coatings. It was shown that polysilazanes can be stabilized after annealing at 550°C. Polysilazane single layers with a thickness below 2 µm are crack-free even after annealing but, unfortunately do not fulfill the dielectric requirements. Single layers with a thickness higher than 2 µm systematically cracked after annealing. With a subtle combination of three layers of polysilazane and a sputtered SiOxAly layer we succeeded in growing a crack-f, (DOCSC01) -- FUNDP, 2014

Brucellae are the agent responsible for a worldwide zoonosis called « brucellosis ». This intracellular bacterium is able to infect professional and non-professional phagocytes. Therein, the infection occurs in two successive stages, composed of an early phase characterized by a stable number of viable bacteria, followed by a proliferative phase. Inside the cell, the bacterium resides in a vacuole, which interacts transiently with the endocytic pathway (carrying the LAMP-1 marker) before reaching its replicative niche, an endoplasmic reticulum-like compartment. All cells, either prokaryotic or eukaryotic, are characterized by a cell cycle. There are two major aspects of the bacterial cell cycle, the replication of the genome and the growth of the bacteria. The bacterial cell cycle occurs in three main stages, first the "newborn" (Nb) stage between cell division and the initiation of genome replication, then the "intermediate" (Int) stage corresponding to growing bacteria without detectable constriction site, and finally the predivisional (Pd) stage. Given the biphasic infectious mode of Brucella abortus, we hypothesized that the progression of its cell cycle could be modulated during infection. However, the Brucella cell cycle in bacterial culture and a fortiori during infection is poorly investigated, as well as its regulation. Such as other Rhizobiales of the -proteobacteria group, Brucella abortus displays a unipolar growth and we took advantage of the TRSE labeling to characterize the "growth" aspect of the cell cycle during infection. Indeeed, this TRSE labelling allows the monitoring of growth for individual bacteria. During this thesis, we showed that during the first 6 h PI, constricting bacteria were almost inexistent and bacterial growth was undetectable. This suggests a non-proliferation and an arrest of the unipolar growth of B. abortus during the first stage of the infection. In addition, the newborn bacteria (originating from a division event) were pr, La bactérie du genre Brucellae est l’agent responsable de la zoonose mondiale appelée “brucellose”. Cette bactérie intracellulaire est capable d’infecter des phagocytes professionnels ou non. L’infection d’une cellule hôte se déroule en deux étapes, la première étant caractérisée par un nombre stable de bactéries vivantes, suivie par une phase de prolifération. Une fois à l’intérieur de la cellule hôte, la bactérie réside dans une vacuole, qui interagit de façon transitoire avec la voie d’endocytose avant d’établir sa niche de prolifération, constituée de compartiments dérivés du réticulum endoplasmique. Toutes cellules, procaryotes ou eucaryotes, sont caractérisées par un cycle cellulaire. Il y a deux aspects majeurs du cycle cellulaire bactérien, la réplication du génome and la croissance bactérienne. Le cycle bactérien se déroule en trois étapes, premièrement la phase « newborn » (Nb) entre la division cellulaire et l’initiation de la réplication du génome, ensuite la phase « intermediate » (Int) correspondant aux bactéries en croissance ne présentant aucun site de constriction détectable et finalement la phase de prédivision (Pd). Etant donné le mode biphasique d’infection de Brucella abortus, nous avons émis l’hypothèse selon laquelle la progression de son cycle cellulaire pourrait être modulée durant l’infection. Cependant, le cycle cellulaire de Brucella et sa régulation in vitro et in vivo ne sont presque pas étudiés. Comme d’autres Rhizobiales du groupe des -protéobactéries, Brucella abortus croît de manière unipolaire. Grâce au marquage TRSE, nous avons caractérisé l’aspect de la croissance bactérienne du cycle cellulaire durant l’infection de cellules hôtes. En effet, ce marquage permet d’observer la croissance pour chaque bactérie individuellement. Au cours de cette thèse, nous avons montré que durant les 6 premières heures après infection, les bactéries présentant un site de constriction sont presque inexistantes et la croissance bactérienne est indéte, (DOCSESG00) -- FUNDP, 2014

Multiple systems, composed of several asteroids rotating around their common center of mass, are common in the solar system but misunderstood. These systems can be very different from each other due to their location, the shape of the bodies or their rotations. In this thesis, we carry out several studies on the subject by considering two types of multiple systems: satellites of asteroids and double asteroids. In the first part, we detect gravitational resonances between an ellipsoid in constant rotation and a point mass. Next, we determine the main resonances surrounding the triple system (87) Sylvia and other triple systems known. The evolution of these systems by tidal effects and BYORP is then analyzed. In the second part, we seek to understand the lack of binary asteroids among Plutinos. Finally, we express the interaction potential in the symmetric trace free tensor formalism and we test it on the double system (66391) 1999 KW4., Les systèmes multiples, composés de plusieurs astéroïdes en rotation autour de leur centre de masse commun, sont nombreux dans le système solaire mais encore méconnus. Ils peuvent être très différents les uns des autres, dû à leur situation, à la forme des corps ou encore à leurs rotations. Dans cette thèse, nous réalisons plusieurs études sur le sujet en considérant deux catégories de systèmes multiples : les satellites d'astéroïdes et les astéroïdes doubles. Dans la première partie, nous détectons les résonances gravitationnelles entre un ellipsoïde en rotation constante et une masse ponctuelle. Nous déterminons ensuite les résonances principales entourant le système triple (87) Sylvia et les autres systèmes triples connus. L'évolution de ces systèmes par les effets de marée et de BYORP est analysée par la suite. Dans la seconde partie, nous cherchons à comprendre la raison du petit nombre d'astéroïdes binaires parmi les Plutinos. Enfin, nous montrons l'adéquation du formalisme des tenseurs symétriques sans trace pour l'expression du potentiel d'interaction et nous testons nos résultats sur le système double (66391) 1999 KW4., (DOCSC00) -- FUNDP, 2014

Beta vulgaris is a biennial plant, which under both vernalization and long photoperiods, shows early flowering during the first growing year. Early flowering of sugar beet results in a reduction of sugar yields. Despite systematic phenotypic counter-selection, early flowering plants are still observed in the fields. The aim of this work was to identify sequence polymorphisms statistically associated with early flowering in sugar beet so they can be used to develop new molecular markers. These markers would contribute to improve breeding and selection for sugar beet varieties more resistant to early flowering. To reach this goal, we followed a candidate gene approach relying on the extensive knowledge of flowering time control available on the model species Arabidopsis thaliana. In our strategy, we first isolated homologous genes related to flowering time control in sugar beet, we then studied their polymorphisms by performing EcoTILLING in contrasted samples originating from the same cultivar (Angeliqua). We finally looked for putative association between the identified genetic polymorphisms and the early flowering phenotype. At the end of this research, we were able to identify SNP and indel polymorphisms in BvGI, BvSUF4, BvPHYB, BvPHYA, BvFT1, BvCRY1, BvFY and BvTINYL2 genes. Following the genotyping of two sets of contrasted sugar beet plants with PAMSA probes, statistically significant associations were confirmed between detected polymorphisms within BvGI, BvSUF4, BvPHYB, BvTINYL2 genes and the early flowering phenotype. In conclusion, the candidate gene approach proved to be a promising method to investigate phenotype / genotype association in sugar beet. Four promising targets were identified in this study. These results might favor the development of improved varieties of sugar beet., (DOCSC03) -- FUNDP, 2014

Since the mid-90s, the principle of functional equivalence has been used as a guideline for the regulation of the information society. Its aim is to give legal value to the use of electronic means during the contractual process. According to this principle, electronic documents or data should be considered as equivalent to paper documents if they fulfil the same functions. For instance, considering the legal requirement of a signature, the idea is to take some distance from paperbased environment and handwritten graphics in order to identify the fundamental functions the signature is supposed to fulfill. In this respect, scholars usually consider that a signature is used as a means to authenticate a person, i.e. to identify her and to give consent. Therefore, any electronic means that ensures the authentication function should be equivalent to a handwritten signature. This reasoning also involves principles such as technology neutrality and non-discrimination. The principle of functional equivalence was adopted in 1996 by the United Nations Commission on International Trade Law (UNCITRAL) in its model law on electronic commerce. Since then, it has been recognized by many lawmakers around the world. Nevertheless, a certain lack of methodology has resulted in diverging initiatives and implementations. In this context, the aim of this study is to build a theory of functional equivalence based on a comparative and interdisciplinary approach. First it identifies the roots, evolution, forces and weaknesses of the principle. Then it develops its conceptual structure and methodology. For a better understanding of the principle, the first part of the study proposes a cartography of the genesis and propagation of the principle, both at the international and national level. It goes back to the Scandinavian origins of the principle and underlines the influence exerted by methods of Value Analysis. The second part of the study proposes a critical and theoretical model based on t, Dans le processus de régulation de la société de l’information, le principe d’équivalence fonctionnelle a été utilisé dès les années 90 pour la reconnaissance juridique des procédés électroniques utilisés dans les relations contractuelles. Selon ce principe, les documents et données électroniques peuvent bénéficier de la même reconnaissance juridique que les documents papier, à condition de remplir les mêmes fonctions. Par exemple, considérant l’exigence légale d’une signature, il s’agit de s’abstraire de l’environnement papier traditionnel et de l’apposition manuscrite d’un graphisme personnel, pour identifier les fonctions que la signature est censée remplir. Dans cette optique, la doctrine admet généralement que la signature doit au moins permettre d’identifier le signataire et d’attester son consentement au contenu de l’acte signé. Dès lors, tout dispositif électronique permettant de remplir ces fonctions d’identification et d’adhésion devrait être équivalent à une signature manuscrite. Cette analyse va de pair avec les principes de neutralité technologique et de non discrimination. Le principe d’équivalence fonctionnelle a été consacré en 1996 par la Commission des Nations Unies pour le Droit Commercial International (CNUDCI), dans sa loi type sur le commerce électronique. Il a connu un immense succès auprès de nombreux législateurs à travers le monde. Toutefois, à défaut de contours précis et d’une méthodologie claire, il a fait l’objet de mises en œuvre sensiblement différentes d’une législation à l’autre. Dans ce contexte, l’étude vise à élaborer une théorie des équivalents fonctionnels, en identifiant ses origines, son évolution, ses forces et ses faiblesses, puis en dégageant sa structure conceptuelle et méthodologique, dans une approche combinant droit comparé et interdisciplinarité. Afin de mieux cerner le principe d’équivalence fonctionnelle, la première partie de l’étude retrace sa genèse et sa propagation sur la scène internationale et au niveau natio, (DOCJURI00) -- FUNDP, 2014

Highly Pathogenic Avian Influenza (HPAI), especially the Asian H5N1 (AsH5N1), and velogenic Newcastle disease (NDV) virus infections are responsible for the two most contagious and economically devastating poultry diseases. Continuous outbreaks and spread of both diseases support the need for efficacious vaccine strategies. However, traditional inactivated vaccines present some well-known shortcomings and Avian Influenza virus (AIV) live vaccination is prohibited. To fight off both viruses at once, live bivalent NDV-vectored vaccines expressing the haemagglutinin of AIV (rNDV-HA) have been developed by reverse genetics. This thesis aimed investigating the vaccine potency of a recombinant NDV-H5 candidate vaccine administrated early in life in the absence or presence of passive immunity. An optimal vaccination schedule was developed by evaluating different vaccination strategies using the rNDV-H5 vaccine through animal challenge experiments during which clinical protection, viral shedding and immune responses were evaluated in specific pathogen free (SPF) chickens. First, different routes of vaccination and doses of vaccine were tested in order to determine the minimal protective dose against challenge with an antigenically close clade 1 AsH5N1 virus, the A/crested_eagle/Belgium/01/2004 strain. A clear dose dependency was observed after 1-day-old vaccination of SPF chickens with 105, 106 and 107 50 % embryo infectious dose (EID50) of vaccine followed by a challenge at 3 weeks of age. The 106 EID50-dose was shown as the minimal protective dose, allowing 90% clinical protection, significant reduced viral shedding and induction of significant NDV and H5 AIV serological responses. However, the H5 humoral response was weak and slow even after boost vaccinations despite good clinical protection and reduced viral excretion, suggesting a role of cellular and mucosal immunity in the induced protection. An ideal vaccine should be protective against a large panel of strains. In, Les virus de la grippe aviaire hautement pathogène (HPAI), et en particulier le H5N1 Asiatique, et de la maladie de Newcastle (NDV) vélogène sont responsables des deux maladies les plus contagieuses et économiquement dévastatrices chez la volaille. Les foyers continus et la propagation des deux maladies supportent la nécessité de stratégies de vaccination efficaces. Cependant, les vaccins inactivés traditionnels (IA) présente des lacunes et l’usage de vaccins vivants IA est interdit. Pour lutter contre les deux virus à la fois, des vaccins vivants NDV-vectorisés bivalents exprimant l'hémagglutinine de l’IA (rNDV-HA) ont été mis au point par génétique inverse. Cette thèse vise à étudier l'efficacité vaccinale d'un vaccin candidat NDV-H5 recombinant administré chez de jeunes poussins, en absence ou présence d'une immunité passive. Tout d'abord, différents schémas de vaccination avec le vaccin rNDV -H5 ont été étudiés à travers des expériences au cours de laquelle la protection clinique, l'excrétion virale et les réponses immunitaires ont été évaluées chez des poulets EOPS (exempt d'organismes pathogènes spécifiés). Différentes voies de vaccination et doses vaccinales ont été testées afin de déterminer la dose minimale protectrice contre un virus Asiatique H5N1 clade 1 antigéniquement proche, la souche A/crested_eagle/Belgium/01/2004. Une claire relation dose-effet a été observée après vaccination chez des poulets EOPS âgés de 1 jour avec 105, 106 ou 107 EID50 de vaccin suivie d'un challenge à 3 semaines d'âge. La dose de 106EID50 a été démontrée comme étant la dose minimale protectrice permettant 90 % de protection clinique, une excrétion virale significativement réduite et l'induction de réponses sérologiques anti-NDV et H5 IA. La comparaison entre les voies d’inoculation oculo-nasale ou d’eau de boisson avec une même dose de vaccin de 106EID50 par animal n'a pas montré de différence significative indiquant que le vaccin utilisé dans le contexte d’une stratégie de va, (DOCSC03) -- FUNDP, 2014

Nowadays the economy relies on companies evolving in an increasingly highly regulated environment, having their operations strongly formalised and controlled, and being often organised following a bureaucratic approach. In such a context, aligning the business operations with the appropriate IT infrastructure is a challenging and critical activity. Without efficient business/IT alignment, these companies face the risk not to be able to deliver their business services satisfactorily and that their image is seriously altered and jeopardised. Among the many challenges of business/IT alignment is the access rights management which should be conducted considering the rising governance needs, such as taking into account the business actors' responsibility. Unfortunately, in this domain, we have observed that no solution, model and method, fully considers and integrates the new needs yet. Therefore, the thesis proposes firstly to define an expressive Responsibility metamodel, named ReMMo, which allows representing the existing responsibilities at the business layer and, thereby, allows engineering the access rights required to perform these responsibilities, at the application layer. Secondly, the Responsibility metamodel has been integrated with ArchiMate to enhance its usability and benefits from the enterprise architecture formalism. Finally, a method has been proposed to define the access rights more accurately, considering the alignment of ReMMo and RBAC. The research was realised following a design science and action design based research method and the results have been evaluated through an extended case study at the Centre Hospitalier de Luxembourg., (DOCSC06) -- FUNDP, 2014

In today's society, cancer is a group of diseases that represents one of the major health problems. Physicians often face cancers that are resistant to conventional treatments. In addition, these treatments are often toxic for patients and at the origin of significant side effects. This is why researchers constantly search for new therapies and new drugs that can enhance the efficiency of current chemotherapy. A large number of interesting molecules for the development of new treatments come from the plant world. Pectin is one of these molecules of interest. It is a polysaccharide found in all higher plant cell wall. Once modified by pH treatment (MCP) or by heat treatment, pectin can induce tumor cell death. However, the type of cell death, the mechanisms involved and the nature of the active fragments are not well known. In this thesis, we aimed at characterizing the type of cell death induced by pectin having undergone a heat treatment. To do so, we used two tumor cell lines, HepG2 and A549 cells. We also tried to identify fragments that yield the cytotoxicity. We have shown that citrus pectin modified by heat treatment (HFCP) induces death of HepG2 and A549 cells. This cell death is different from classical apoptosis since we did not observe caspase-3 activity in HepG2 cells and we did not observe DNA cleavage in both cell types. Inhibition of caspases by Z-VAD-fmk did not affect HFCP-induced cell death in HepG2 cells, indicating that heat modified citrus pectin could induce caspase-independent cell death. We also showed that heat fragmented citrus pectin induced ubiquitination of intracellular proteins in HepG2 cells and an early induction of autophagy. The study of putative pectic fragment receptors did not allow us to identify the receptor capable of binding the active fragments. However, it allowed us to demonstrate that MCP fragments and HFCP have a different nature since the invalidation of galectin-3, which is able to recognize the MCP fragments, does not, (DOCSC03) -- FUNDP, 2014

Le sujet de cette thèse évalue la possibilité de délimiter des terroirs géochimiques sur le territoire de l’actuelle Belgique, à partir de l’étude géochimique des formations argileuses. Ce questionnement trouve son origine dans la problématique de la détermination de provenance des céramiques communes gallo-romaines. La comparaison des compositions géochimiques d’argiles sensu lato et de céramiques communes provenant de sites de consommation mettrait en évidence les plus fortes ressemblances, ce qui désignerait la région d’origine : un des terroirs géochimiques. Pour démêler la possibilité de délimiter des terroirs géochimiques, les trois autres problématiques suivantes ont dû être résolues. D’une part, distinguer les différentes formations argileuses à potentiel céramique (utilisation au tour) entre elles sur base de leur composition géochimique. Ceci a pu être démontré par l’analyse des compositions géochimiques pour sept formations argileuses dont le potentiel céramiques avait été évalué auparavant sur un ensemble de quinze formations échantillonnées ; Ensuite, identifier la matière première de groupes de référence céramique de sites de production, ce qui n’avait, jusqu’à ce jour, pu être fait. Trois ateliers de potiers de la Cité des Tongres (Amay, Liberchies et Tirlemont), fabriquant de la céramique commune et situés dans des contextes géologiques différents, ont été choisis pour faire l’objet d’une caractérisation archéométrique poussée de leur production. Les résultats montrent que dans chaque officine il y a eu mélange de deux types d’argile pour la fabrication des pâtes : une des argiles utilisées est à chaque fois une argile de type smectitique, plutôt riche en fer (Fe2O3≥ 3 %) et l’autre argile est une argile de type kaolinitique, assez pauvre en fer (Fe2O3≤ 3 %). Enfin, distinguer les productions d'ateliers exploitant des formations argileuses différentes. Ceci a pu être démontré sur la base de l’étude des productions des trois officines étudiées. Les ré, (DOCSC04) -- FUNDP, 2014

This thesis aims at developing an agent-based micro-simulation framework for (large) population evolution and mobility behaviour. More specifically we focus on the agents generation and the traffic simulation parts of the platform, and its application to Belgium. Hence we firstly develop a synthetic population generator whose main characteristics are its sample-free nature, its ability to cope with moderate data inconsistencies and different levels of aggregation. We then generate the traffic demand forecasting with a stochastic and flexible activity-based model relying on weak data requirements. Finally, a traffic simulation is completed by considering the assignment of the generated demand on the road network. We give the initial developments of a strategic agent-based alternative to the conventional simulation-based dynamic traffic assignment models., (DOCSC00) -- FUNDP, 2014

In many markets, being competitive echoes with the ability to propose customized products at the same cost and delivery rates as standard ones. As a result, companies provide their customers with online Web configurators to facilitate the product customization task. Web configurators offer a highly interactive configuration environment for customers to specify products that match their individual requirements and preferences. They provide capabilities to guide the customer through the multi-step and non linear configuration process, check consistency, and automatically complete partial configuration. To get a better grasp of what is the current practice in engineering Web configurators, we conducted a systematic empirical study of 111 configurators. We quantified their numerous properties, categorized patterns used in their engineering, and highlighted good and bad practices. We provided empirical evidence that Web configurators are complex information systems. Despite of this fact, this study revealed the absence of specific, adapted, and rigorous methods in their engineering. The lack of dedicated methods for efficiently engineering Web configurators leads to reliability, runtime efficiency, and maintainability issues. To migrate legacy Web configurators to more reliable, efficient, and maintainable solutions, we offer to systematically re-engineer these applications. This encompasses two main activities: (1) reverse engineering Web configurators to extract their configuration-specific data and encoding it into dedicated formalisms, and then (2) forward engineering new improved configurators. In this study, we are concerned with the reverse-engineering process. We developed a consistent set of methods, languages and tools to semi-automatically extract configuration-specific data from the Web pages of a configurator. Such data is stored in variability models (e.g., feature models). These models can later be used for verification purposes (e.g., checking the complet, (DOCSC06) -- FUNDP, 2014

In many markets, being competitive echoes with the ability to propose customized products at the same cost and delivery rates as standard ones. As a result, companies provide their customers with online Web configurators to facilitate the product customization task. Web configurators offer a highly interactive configuration environment for customers to specify products that match their individual requirements and preferences. They provide capabilities to guide the customer through the multi-step and non linear configuration process, check consistency, and automatically complete partial configuration. To get a better grasp of what is the current practice in engineering Web configurators, we conducted a systematic empirical study of 111 configurators. We quantified their numerous properties, categorized patterns used in their engineering, and highlighted good and bad practices. We provided empirical evidence that Web configurators are complex information systems. Despite of this fact, this study revealed the absence of specific, adapted, and rigorous methods in their engineering. The lack of dedicated methods for efficiently engineering Web configurators leads to reliability, runtime efficiency, and maintainability issues. To migrate legacy Web configurators to more reliable, efficient, and maintainable solutions, we offer to systematically re-engineer these applications. This encompasses two main activities: (1) reverse engineering Web configurators to extract their configuration-specific data and encoding it into dedicated formalisms, and then (2) forward engineering new improved configurators. In this study, we are concerned with the reverse-engineering process. We developed a consistent set of methods, languages and tools to semi-automatically extract configuration-specific data from the Web pages of a configurator. Such data is stored in variability models (e.g., feature models). These models can later be used for verification purposes (e.g., checking the complet, (DOCSC06) -- FUNDP, 2014

Currently, the investigation of protein refolding processes involves several time-consuming steps that require large amout of protein. In that context, it has been reported that 2-methyl-2,4-pentanediol (MPD) is able to modulate the denaturing properties of sodium dodecyl sulfate (SDS) and to induce the refolding of proteins. Nonethless and even though this cosolvent effect was previously observed on the refolding of several proteins (including the lysozyme, the carbonic anhydrase, and PagP), little is known about the mechanism by which the MPD can turn the unfolding properties of SDS. The general objective of this thesis was therefore to go deeper in the understanding of the related mechanisms. In that context, a 4-steps strategy was developed: (i) the protcol was extended to the trimeric membrane protein Omp2a in order to demonstrate the transferability of the method to a multimeric protein and determine the optimal detergent/cosolvant ratio. (ii) The combination of experimental (biophysic spectroscopies) and theoretical (molecular dynamics) outputs gives us the opportunity to describe the SDS-induced unfolding states of model peptides. (iii) Then, the key role of MPD to induce the SDS micelle dissociation was unveiled by dynamic light scattering and molecular dynamics simulations. (iv) Finally, the refolding of model peptides was investigated in the presence of the detergent and the cosolvent., La compréhension du phénomène de repliement constitue un défi majeur en biochimie structurale et en biophysique des protéines: la connaissance des mécanismes par lesquels les protéines adoptent une structure 3D particulière peut aider à comprendre et/ou prédire les fonctions des protéines. Il n'existe actuellement aucune méthode générale permettant de replier et caractériser une protéine. En effet, bien que de nombreux protocoles soient référencées dans la littérature, l'étude d'une nouvelle protéine fait, presque toujours, intervenir de nombreuses étapes préliminaires afin d'identifier les conditions permettant son repliement. Dans ce contexte, une méthode originale a récemment été mise en évidence, associant un détergent, le sodium dodécyle sulfate (SDS; connu pour ses propriétés dénaturantes), à un cosolvant, le 2-méthyle-2,4-pentanediol (MPD). Bien que cette combinaison ait préalablement été appliquée avec succès afin d'induire la renaturation de différentes protéines (lysozyme, anhydrase carbonique et PagP), les mécanismes associés sont encore peu connus. L'objectif général de cette thèse est donc d'améliorer les connaissances générales afin de pouvoir optimiser la méthode. Pour cela, une stratégie en quatre temps a été suivie: (i) L'utilisation de l'Omp2a comme modèle de protéine membranaire multimérique a permis d'identifier le rapport de concentrations entre le détergent et le cosolvant menant à un repliement optimal de la protéine. (ii) En combinant des études expérimentales (mesures biophysiques) et théoriques (dynamique moléculaire), il a été possible de caractériser le processus de dénaturation de peptides modèles dans le SDS. (iii) La dissociation de micelles de SDS par le MPD a ensuite été mise en évidence par des mesures en diffusion lumineuse dynamique et des simulations en dynamiques moléculaires. (iv) Finalement, le repliement des peptides solubles en présence du couple SDS/MPD a permis de mettre en évidence le rôle clé du MPD pour protéger les pep, (DOCSC02) -- FUNDP, 2014

Wistar-Furth (WF) rats are a strain of rats usually employed in models of full major histocompatibility complex-mismatched kidney transplantation. These were demonstrated to be resistant to several models of chronic kidney disease. In our study, we investigated their potential resistance to a renal ischemia-reperfusion (I/R) injury in comparison to another strain, Wistar-Hanover (WH) rats. Anesthetized male WH and WF rats were submitted to I/R by occlusion of the left renal artery, followed by contralateral nephrectomy. Urine, blood and tissue samples were collected at different time-points post-I/R to evaluate renal function, inflammation and tubular injury along with the determination of the NO synthase expression. In post-ischemic WF rats, the renal function was better preserved than in the post-ischemic WH rats. In addition, the post-ischemic WF rats presented less inflammation than the WH rats. These observations were associated with the maintenance of the nNOS expression along with a lower induction level of iNOS expression in WF rats than in WH rats. Moreover, WF rats excreted also a significant smaller amount of TxB2. In conclusion, our results showed that WF rats were more resistant to an I/R injury than WH rats. This could be explain to the differential regulation of intrarenal NOSs expression as well as the TxA2 production., En guise d’introduction de ce projet de recherches, rappelons que de nos jours, l’insuffisance rénale aiguë (IRA) reste un problème de santé publique majeur corrélé avec des taux de morbidité et de mortalité élevés. En particulier, la nécrose tubulaire aiguë (NTA) consécutive à l’ischémie/reperfusion (I/R) du rein constitue l’une des causes majeures du développement de l’IRA. L’insuffisance rénale aiguë post-ischémique détermine une entité clinique complexe, associant de nombreux médiateurs et processus différents. Ce type de pathologie est à l’origine d’altérations du tissu rénal qui compromettent les mécanismes de régulation homéostasiques. Parmi les multiples intervenants potentiels impliqués dans les diverses étapes qui conditionnent le devenir du rein post-ischémique, on peut citer notamment le monoxyde d’azote (NO) et les métabolites de l’acide arachidonique. Dans ce contexte, l’objectif de ce projet était d’explorer les rôles de certains médiateurs, comme le NO ou le thromboxane, dans le développement de l’IRA post-ischémique. 1°) Dans un premier volet expérimental mis en œuvre afin de rencontrer les objectifs de cette étude, la méthodologie a consisté à induire une insuffisance rénale ischémique chez deux souches de rat, à savoir le rat Wistar Hanovre (WH), communément utilisé en expérimentation animale et le rat Wistar Furth (WF). Notre choix s’est porté sur cette dernière souche car elle se caractérise par la particularité de présenter une résistance naturelle à différents modèles d’insuffisance rénale chronique (IRC) (Sciotti et Galant, 1987 ; Fitzgibbon et al. 1999 ; Erdely et al., 2003, 2004, 2006), notamment associée à un maintien de la production du NO. Les résultats obtenus au cours de cette approche expérimentale indiquent que la concentration plasmatique de la créatinine et l’excrétion urinaire de NGAL, deux biomarqueurs de l’insuffisance rénale, sont moins perturbés en conditions post-ischémiques chez le rat WF que chez le rat WH, ce qui suggère q, (DOCMED02) -- FUNDP, 2014

Nowadays, deposition of thin films is one way to completely refashion our well-known glasses, metals and semiconductors. Among deposition techniques, the ones using plasma – the fourth state of matter or the ionized gas – have many advantages. The deposited coating is tightly adherent to its substrate, covers it completely and can have a large diversity of tunable properties. Plasma polymerization is one of them, allowing the thin film production of plastic, or polymeric, material. The present work investigated the low-pressure plasma polymerization in a radio-frequency reactor with planar inductive power coupling. The monomers studied were styrene (C8H8), benzene (C6H6), ethylene (C2H4) and acetylene (C2H2), which are pure hydrocarbons, but also methyl methacrylate (C5H8O2 - MMA) which contains oxygen. The neutral by-products of their plasmas were investigated by mass spectrometry (MS) downstream of the discharge. In the case of styrene and MMA, the elemental composition of the plasma-deposited polymers was measured by X-Ray Photoeletron Spectroscopy (XPS) and the deposition rate by contact profilometry. The main results of the thesis are the following. • A systematic approach based on low electron impact energy and Threshold Ionization Mass Spectrometry (TIMS) allowed an extensive species identification of the by-products. To explain the many new species detected, light-weighted carbon containing radicals with low hydrogen content are proposed as intermediates of reaction. In the case of MMA, the dominating species suggested that oxygen containing radicals are not likely to participate to recombination reactions. • In addition, the partial pressures of the dominant species were quantified by MS in the discharges of styrene, benzene, ethylene and acetylene. Varying the plasma power revealed a systematic and large content of hydrogen and acetylene in the discharge. Effects due to hydrogen were proposed to explain the lower depletion of ethylene compared to the three, (DOCSC01) -- UNamur, 2014

Issues of secrecy and anonymity back repeatedly in a series of topics related to parentage and procreation : adoption, birth secret, assisted reproduction with donor, surrogacy, incest, DNA test. Has the legislator the right to deny a human being to know where it comes from? Should the law recognize and ensure to all individuals the right to know his maternal and paternal origins? On an international scale, should we recognize a human right to know the origins of his lineage? And besides, what is meant by “origins”? These are the various questions that the thesis tries to meet, in an approach combining comparative and multidisciplinary, before developing a model for resolving conflicts that may arise between the right of an individual to know its origins and the right of others persons, more specifically the one of the biological parents but also of legal parent (adoptive parents, authors of parental project, …), to privacy. This model is based on the technique of balancing of interests and is founded on the case law of the European Court of Human Rights. Built around a gradation in the lifting of the secrecy of origins, based on both the context in which the secret is laying, on the different levels of the search for identity and the need to respect the interests of the child, this model is established by reference to Belgian law which he revealed some gaps that the thesis tries to overcome de lege lata and de lege ferenda. It is intended to apply equally beyond Belgian borders as it seems crucial that each State makes the maximum progress towards the recognition and enforcement of the right of every person to know its origins., Les questions du secret et de l’anonymat reviennent de manière récurrente dans une série de sujets liés à la filiation et à la procréation : adoption, accouchement secret, procréation médicalement assistée avec donneur, gestation pour autrui, inceste, empreintes génétiques. Le législateur a-t-il le droit de refuser à un être humain de savoir d’où il vient ? La loi devrait-elle reconnaître et garantir à tout individu le droit de connaître ses origines maternelle et paternelle ? Sur le plan international, devrait-on reconnaître un droit de l’homme à connaître les origines de sa filiation? Et d’ailleurs, qu’entend-on par « origines » en droit de la filiation ? Ce sont ces diverses interrogations que la thèse tente de rencontrer, dans une approche combinant droit comparé et multidisciplinarité, avant d’élaborer un modèle normatif de résolution des conflits pouvant survenir entre le droit d’un individu à la connaissance de ses origines et le droit des tiers, plus spécifiquement celui de ses parents d’origine mais aussi de ses parents juridiques (adoptants, auteurs du projet parental, parents d’intention), au respect de leur vie privée. Ce modèle s’appuie, dans une perspective de conciliation des droits fondamentaux, sur la technique de la pondération des intérêts et s’inspire de la jurisprudence de la Cour européenne des droits de l’homme. Construit autour d’une gradation dans la levée du secret des origines, qui se fonde à la fois sur le contexte dans lequel le secret se pose, sur les différents niveaux de la quête identitaire et sur le nécessaire respect de l’intérêt de l’enfant, ce modèle est établi par référence au droit belge dont il fait apparaître certaines lacunes que la thèse tente de pallier de lege lata et de lege ferenda. Il a vocation à s’appliquer également au-delà de nos frontières tant il paraît crucial que chaque Etat fasse le maximum pour progresser vers la reconnaissance et l’application du droit de chacun à connaître ses origines., (DOCMED01) -- UNamur, 2014

The 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway for isoprenoid biosynthesis has come under increased scrutiny as a target for novel antimalarial, antibacterial and antituberculosis agents. 1-Deoxy-D-xylulose 5-phosphate reductoisomerase (DXR) is a key enzyme of the pathway that catalyzes the rearrangement and nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reduction of 1-deoxy-D-xylulose 5-phosphate (DXP) to MEP. The unique properties of DXR make it a remarkable and rational target for drug design. First, it is a vital enzyme for synthesis of isoprenoids in algae, plants, several eubacteria including the pathogenic bacteria like Bacillus anthracis, Helicobacter pylori, Yersinia pestis, Mycobacterium tuberculosis and the malarial parasite, Plasmodium falciparum. Second, there are no functional equivalents to DXR in humans, making it an attractive target for therapeutic intervention. Third, DXR appears to be a valid target and the results from fosmidomycin, the only available DXR inhibitor under clinical trials, suggests synergistic effects with the lincosamide antibiotics, lincomycin and clindamycin. Despite drug design efforts in this area, no successful drug specifically designed to inhibit DXR has emerged yet. Recently, it has been shown that Fosmidomycin inhibited growth of B. abortus cells expressing the Escherichia coli GlpT transporter (required for fosmidomycin uptake), confirming that a DXR-like (DRL) activity exists in these bacteria. The B. abortus DRL protein was found to belong to a family of uncharacterized proteins similar to homoserine dehydrogenase. Our work was focus on the production, purification and characterization of the E. coli DXR enzyme and the B. abortus DRL enzyme. This allowed us to study three series of analogs of fosmidomycin, a specific competitive inhibitor of DXR, available through collaboration with the University of Gent (Prof S.VanCalenberg). Two approaches were used to characterize interaction between inhibito, (DOCSC02) -- FUNDP, 2014

Because of the appearance of more and more bacteria resistant to antibiotics, it is an urgent need to find new antibacterials. Several approaches have developed in the last few years such as antivirulence. This strategy is based on the weakening of the bacteria rather than killing it. Therefore, we interested in this principle and we developed new antibacterials to combat the bacterial virulence. We based our approach on multivalent scaffolds, as the multivalency is well know to improve the inhibition and/or activation of biological processes. We synthesized new multimeric compounds such as glycofullerenes, glycopillararenes and glycorotaxanes. We showed that these molecules are good inhibitors of glycosyltransferases and lectins, multivalent effects were observed in several cases., (DOCSC02) -- FUNDP, 2014

In many sources of positive law, freedom of the press has been the subject of a special consecration beyond the general recognition of freedom of expression. This is true in the Belgian Constitution (article 25), in the American Bill of Rights (First Amendment), as well as in the case law of the European Court of Human Rights (based on Article 10 of the European Convention on Human Rights). What is the meaning of freedom of the press? If it is universally recognized that this freedom is essential to the functioning of a democratic society, there is no agreement on its practical meaning. To consider that this freedom is more than a mere redundancy, what could be its scope and legal surplus? This is the subject of the present study. The current media environment is conducive to such an analysis. On the one hand, the emergence of the Internet and, more recently, the advent of the participatory Web have democratized the large-scale expression, enabling a large range of new players to contribute, alongside journalists, to the information of the public (« citizen journalists », NGOs, political parties, environmental advocacy groups, human rights organizations, etc.); on the other hand, an increasing technological convergence seems devote all traditional media of expression (texts, sounds, images, audiovisual contents) to be found on the Internet in a digital form. The first part of the study seeks to define the respective scope of freedom of expression and of freedom of the press, both in Belgian law and in the case law of the European Court of Human Rights. The analysis reveals that a distinction between the two freedoms cannot be based on the use of a particular medium of expression or on the status of the person who claims freedom of the press to his advantage. The second part of the study is aimed at proposing a definition of freedom of the press and at analyzing the different rules that apply to the press in the light of such a definition. By taking support on reflec, Dans de nombreuses sources de droit positif, la liberté de la presse a fait l’objet d’une consécration particulière au-delà de la reconnaissance générale de la liberté d’expression. Ainsi en va-t-il de la Constitution belge (article 25), du Bill of Rights américain (Premier Amendement), comme de la jurisprudence de la Cour européenne des droits de l’homme (qui s’est construite sur le terrain de l’article 10 de la Convention européenne des droits de l’homme). Que signifie la liberté de la presse ? S’il est universellement reconnu que cette liberté est essentielle au fonctionnement d’une société démocratique, il n’y a pas d’accord sur sa signification concrète. A considérer que cette liberté constitue plus qu’une simple redondance, quel pourraient être ses contours et son surplus juridique ? Le contexte médiatique actuel est propice à une telle analyse. D’une part, l’émergence récente de l’internet et celle, plus récente encore, du Web participatif, ont démocratisé l’expression à grande échelle, permettant ainsi à une foule de nouveaux acteurs de contribuer, aux côtés des journalistes, à la mission d’information du public (« journalistes citoyens », ONG, partis politiques, associations de défense de l’environnement, organisations veillant au respect des droits de l’homme, etc.) ; d’autre part, une convergence technologique croissante semble vouer l’ensemble des supports traditionnels d’expression (textes, sons, images, contenus audiovisuels) à se retrouver sur la Toile sous une forme numérique. La première partie de l’étude vise à définir les contours respectifs de la liberté d’expression et de la liberté de la presse en droit belge et dans la jurisprudence de la Cour européenne des droits de l’homme. L’analyse révèle qu’une éventuelle distinction entre les deux libertés ne peut être fondée sur l’utilisation d’un support d’expression particulier ou sur le statut de la personne qui revendique la liberté de la presse à son profit. La seconde partie de l’étude vise à pro, (DOCJURI00) -- UNamur, 2014

This thesis concentrates on infringing (non-slavish) similarity in three main domains of intellectual property law, namely trademarks, designs and models, and copyright. Traditionally, the infringing similarity between two objects – as far as the form is concerned - is treated differently depending on the specific right involved. The respective regimes differ on a number of essential points: theoretical criteria for assessing the infringement (likelihood of confusion, similar overall impression, taking over of original elements); relevant public; functions of the right; consideration for the particular products or services at stake. Moreover, the apparent divergences at the level of the scope of protection seem to be closely related to essential differences at the level of the access to the protection. The substantive conditions to benefit from the protection are generally considered to be unlike: distinctive character, novelty and individual character, and originality. At the basis of this study, there is the idea that the distance between the respective IP-regimes might not as important as it is usually said. The thesis examines the feasibility of a convergence in two steps, mainly in the light of the jurisprudence of the Court of justice of the European Union. The first part of the thesis is dedicated to the conditions of the protection. It is suggested that the notion of originality in a broad sense plays a relevant role under the three regimes. The second part of the study is dedicated to the scope of protection. It is argued that the criterion of similar overall impression constitutes a relevant test in the three domains. Moreover, the thesis takes the view that the assessment of the similarity between the conflicting objects should focus in the first place on the objects as such rather than on the specific rules that are allegedly applicable to the case. Various examples are developed to illustrate that the final outcome of the assessment should not be that d, (DOCJURI00) -- UNamur, 2014

Cancer is a leading cause of death worldwide and the number of deaths due to this disease is increasing from year to year. Unfortunately, lung cancer has the highest mortality rate among all types of cancers, in Belgium or worldwide. Thus, it is essential to improve treatments already in use and to develop new modalities to fight cancer. Radiotherapy plays an important role in cancer treatment since about 50% of all cancer patients will undergo at least one radiotherapeutic session during their illness. Any improvement in radiotherapy may therefore be of benefit for a large number of patients. One way to improve radiotherapy is to maximize the dose delivered to the tumour while minimizing damages to healthy tissues. Hadrontherapy has the advantage to spare normal tissues surrounding the tumour because of the particular ballistic of charged particles, which is characterized by the Bragg peak. Indeed, charged particles release most of their energy at the end of their track in the matter whereas the energy deposition of photons (X-rays) is intense at the entrance in the tissues and decreases exponentially with depth. Another way to improve radiotherapy is to limit tumour radioresistance by increasing our knowledge of the radioresistance mechanisms in order to disrupt them. It has been demonstrated that tumour cells are able to protect tumour associated endothelial cells by secreting growth factors which inhibit endothelial cell apoptosis and promote angiogenesis. A reciprocal dialogue seems also to occur. Consequently, the therapeutic effect of ionizing radiations is limited. In the first part of this work, we compared the effects of X-ray and alpha particle irradiations on tumour cells, derived from a lung cancer, and endothelial cells. We demonstrated that alpha particles were more effective that X-rays and that mitotic catastrophe was the main type of cell death induced by both types of irradiation. We also demonstrated that X-ray and alpha particle irradiations ind, La radiothérapie occupe une place importante dans le traitement contre le cancer. Un grand nombre de patients pourrait donc profiter de l’amélioration des traitements radiothérapeutiques. L’hadronthérapie possède l’avantage de mieux épargner les tissus sains environnants par rapport à la radiothérapie conventionnelle qui utilise des rayons X, grâce à la balistique particulière des particules chargées. Ainsi, l’essentiel de l’énergie de la particule est déposé à la fin du parcours de celle-ci contrairement aux photons (rayons X) qui perdent leur énergie tout au long de leur trajet. Une autre piste pour améliorer la radiothérapie serait de limiter la résistance des tumeurs aux radiations ionisantes en étudiant plus avant les mécanismes responsables de cette radiorésistance. En effet, un dialogue réciproque entre cellules tumorales et cellules endothéliales, via la sécrétion de facteurs de croissance et de cytokines, peut limiter les effets thérapeutiques des radiations ionisantes. Le premier objectif de cette thèse était donc de comparer les effets des rayons X et des particules alpha sur des cellules tumorales et des cellules endothéliales. Nous avons montré que les particules alpha sont plus efficaces que les rayons X et que la mitose catastrophique est le principal type de mort induit par ces deux types de radiation. Nous avons également montré que les irradiations par particules alpha et par rayons X induisent la surexpression de gènes impliqués dans la mort cellulaire, l’angiogenèse et l’inflammation. La seconde partie de ce travail consistait à mettre au point un système de co-culture permettant d’étudier le dialogue entre les cellules tumorales et les cellules endothéliales après irradiation au moyen de particules alpha. Nous avons à nouveau mis en évidence des changements d’expression de gènes codant pour des protéines pouvant être impliquées dans un dialogue entre les deux types cellulaires et pouvant conduire à des phénomènes de radiorésistance ou inversemen, (DOCSC03) -- FUNDP, 2013

The synthesis of nanostructured ZnO has attracted considerable attention worldwide because of its practical and potential applications. Numerous low-dimensional ZnO nanostructures, such as nanotubes, nanowires, nanobelts, nanorods, etc. have been synthesized. Whilst improvements in performance can be observed in such nanomaterials over bulk ZnO, it is expected that hierarchically structured ZnO can increase performances further still as the advantages of nanoscale structuration can be combined with the advantages of micro and macrostructuration on different length scales. However, investigations on synthesis, characterization, and applications of hierarchically nanostructured ZnO are scarce. The objectives of this thesis are to design and synthesize a series of hierarchically structured ZnO, and to evaluate their potential in photocatalytic applications. The scientific strategy for the synthesis of hierarchically structured ZnO is to design suitable synthesis routes based around various zinc sources available. In this thesis, two different types of zinc sources, organic (i.e. dimethylzinc and zinc acetate) and inorganic (i.e. zinc nitrate and zinc chloride), have been employed to synthesize hierarchically structured ZnO. A series of hierarchical ZnO have been successfully achieved by adopting various synthesis methods. The obtained hierarchically structured zinc oxides were characterized in detail by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), N2 adsorption-desorption measurements, room-temperature photoluminescence spectroscopy (RT-PL), and thermogravimetry and differential scanning calorimetry (TG-DSC). Based on these characterizations, formation mechanisms were reasonably proposed. Finally, the photocatalytic performances of the as-synthesized hierarchically structured ZnO materials were investigated by examining the photodegradation of Rhodamine B (RhB) under UV light in the presence of these materials. Th, La synthèse de nanostructures en ZnO attire considérablement l’attention mondiale de part ces applications actuelles et potentielles. De nombreuses nanostructures mono- ou bi-dimensionnelles, tels que les nanotubes, nano-files, ou encore les nano-cloches, ont été synthétisées avec succès. Comparativement à ces structures, les structures hiérarchisées pourraient présenter des propriétés supérieures grâce à leur structure fines et stable. Néanmoins, les recherches sur la synthèse et la caractérisation de nanostructures hiérarchisées en ZnO sont moins rapportées dans la littérature scientifique. L’objectif de cette thèse consiste à synthétiser, d’une part, une série de nanostructures hiérarchisées en ZnO et d’autre part, à étudier leurs propriétés photocatalytiques. La stratégie scientifique pour la synthèse de ces structures repose sur différentes voies d’assemblage utilisant une variété de source de Zn, en particulier le diméthyl de zinc, le di-acétate de zinc et d’autres sources inorganiques. Les structures obtenues ont été caractérisées par la diffraction de rayon X (DRX), la microscopie électronique à balayage (MEB), la microscopie électronique à transmission (MET), la technique d’adsorption-désorption d’azote, la photoluminescence (PL) et la thermogravimétrie (TG-DSC). Sur base de ces caractérisations, une proposition mécanistique a pu être dégagée. De plus ; les performances photocatalytiques des matériaux ont été investigués via la photodégradation de la Rhodamine B (RhB) sous l’action d’une lumière UV. Le présent travaille démontre que les structures hiérarchisées en ZnO pourraient être générés et contrôlés en fonction du choix de la source de Zn. De plus, cette thèse démontre que ces mêmes structures présentent des propriétés optiques et photocatalytiques. Cette stratégie scientifique pourrait être étendue à la synthèse de nanostructures à base d’autres oxydes métalliques., (DOCSC02) -- FUNDP, 2013

This thesis contains two principal axes, namely the development of statistical and bioinformatics analyses of data from DNA chip analyses, and their application on biological data relative to the development of metastases induced by hypoxia. The different statistical and bioinformatics analyses are based on work previously performed in our lab for which we brought our contribution, as well as new innovative work performed in the course of this thesis. First, we used a dataset retrieval tool (PathEx) to gather the datasets better suited to our goals. Then, using the results obtained in a benchmarking analysis of single gene statistical analysis methods, we analyzed these datasets using the best suited method. An innovative meta-analysis step performed on the results of the first analyses allowed us to detect differentially expressed genes recurrent in the datasets tested. Then, an over-representation analysis step was performed on the pathways contained in KEGG that allowed to sort the genes obtained at the previous step according to their biological function. In parallel, we developed a new geneset analysis method (FAERI), allowing to statistically test groups of genes biologically related, instead of individual genes. The comparison of the results of the two axes highlights groups of genes supposedly involved in the biological situations tested. The application of these different steps on data related to metastasis and hypoxia allowed us to identify several hundred candidate genes, distributed in tens of pathways. A significant part of these genes are in accordance with recent literature. Moreover, we highlighted the implication of the spliceosome pathway in the metastasis process, which was previously unknown. 20 new candidate genes were identified in this particular pathway. These results suggest the implication of alternative splicing in the development of metastasis. We have developed a statistical and bioinformatics analysis sequence allowing the highlighting, Cette thèse comporte deux axes principaux, à savoir la mise en place d’outils bioinformatiques et statistiques d’analyse de données obtenues à l’aide de puces à ADN, ainsi que leur application à des données relatives au phénomène métastatique induit par l’hypoxie. Les différentes analyses bioinformatiques et statistiques développées s’appuient sur un savoir-faire qui a été construit au cours des dernières années et propre à notre laboratoire, auquel nous avons apporté notre participation ; ainsi que sur plusieurs contributions innovantes réalisées au cours de cette thèse. Dans la première partie, nous avons utilisé une base de données (PathEx) afin de sélectionner les jeux de données les plus adaptés aux recherches que l’on souhaite effectuer. Ensuite, grâce à un outil de mesure des performances des analyses statistiques « single gene » que nous avons développé, nous avons sélectionné la méthode la plus adaptée aux différents jeux de données. L’utilisation d’une étape innovante de méta-analyse sur ces résultats et une analyse de sur-représentation effectuée sur les voies de signalisation contenues dans KEGG, nous ont alors permis respectivement d’identifier des gènes différentiellement exprimés de façon récurrente au sein des jeux de données et de trier ces gènes par fonction biologique. Parallèlement à cet axe d’analyse « single gene », nous avons développé une méthode d’analyse « geneset », appelée FAERI, permettant l’analyse statistique de groupes de gènes biologiquement reliés au lieu de gènes pris individuellement. La mise en commun des résultats de ces deux axes d’analyse (single gene et geneset) affine l’identification de groupes de gènes supposés être impliqués dans la problématique étudiée. L’application de ces différentes étapes d’analyses sur des données relatives au phénomène métastatique et à l’hypoxie nous a permis d’identifier plusieurs centaines de gènes candidats, répartis dans plusieurs dizaines de voies de signalisation. Il est à noter qu’une gran, (DOCSC03) -- FUNDP, 2013

During the democratisation process in the second and fourth waves of democratisation, most African countries decided to implement the supervision of their armed forces through the pattern of democratic control, a kind of liberal civil-military relations which is increasingly being adopted worldwide. The first paradox which occurred in these countries is that they are not yet democratic States but they claim to have democratic control of their armed forces. Second, despite the existence of a civilian Rule, the armies are still a threat to the process of democratisation because the overthrow of the government by the army could be done at any moment; for this reason, some civil and military authorities tend to use, in practice, “subjective control” to secure the political power. Taking into consideration the context and the use of non democratic tools in the management of security forces, one cannot really scrutinise the civil-military relations in these countries on the basis of the model of democratic control. Therefore, to study the cases of Burkina Faso and Senegal (1960-2012), I propose to use a model of semi-democratic control of the armed forces. This model takes due account not only of the formal mechanisms of control, but also of the informal tools including the “subjective control”, as well as of the sociopolitical context of building up of that control., Le contrôle des forces armées dans les pays en démocratisation fait face à des paradoxes. Ces États ont certes adopté le modèle de contrôle démocratique à l’occasion de leur processus de démocratisation, mais ils n’ont pas totalement renoncé à certaines pratiques de « contrôle subjectif » et font, de surcroît, face à un déficit démocratique. Dans ces conditions, il n’est guère possible de cerner, dans ces pays, la gestion réelle de l’armée sur la base du contrôle démocratique. Nous avons donc proposé, dans le cadre des théories des relations civilo-militaires, un modèle de contrôle semi-démocratique afin de mieux saisir la complexité du contrôle des forces armées dans les pays en démocratisation en général et spécifiquement au Burkina Faso et au Sénégal (1960-2012). A travers le contrôle semi-démocratique, nous montrons que le contrôle des forces armées est le produit des réalités sociales, politiques et institutionnelles propres à une société donnée. Dans le contexte de démocratisation, en particulier, il se produit un type de contrôle sui generis articulé autour d’un contrôle institutionnel formel fondé sur le modèle de contrôle démocratique d’une part et d’un contrôle informel parmi lequel figure le « contrôle subjectif » censé être un moyen de sécurisation face aux menaces de déstabilisation des forces armées d’autre part. Le contexte sociopolitique est également un autre élément pertinent dans l’expression du contrôle semi-démocratique., (DOCSESG02) -- FUNDP, 2013

The aim of this work was the study of collisional parameters of hydrocarbon lines such as ethane, allene and methane, from low to high temperatures. The determination and the study require the precise knowledge of the spectral parameters of absorption lines, in particular the collisional broadening coefficients, on a wide range of temperature. In this context, we studied different gas mixture presenting an interest for the study of our atmosphere as well as that of Titan. First, to measure these parameters for temperature up to room temperature, we have conceived, developed and realized the set up of an "high temperature" absorption cell allowing spectroscopic studies of line profiles and collisional parameters of gaseous molecules between 300 and 750 K. With the help of this device and of low-temperature absorption cells developed previously in the Laboratory Lasers and Spectroscopies of the University of Namur, we measured the collisional broadening coefficients of infrared absorption lines of hydrocarbons as well as their temperature dependences. Nine gas mixtures have been studied : ethane (C2H6−O2, C2H6−air), allene (C3H4−C3H4, C3H4−N2, C3H4−O2, C3H4−air) and methane (CH4−N2, CH4−O2 et CH4−air). The spectra have been recorded in the Laboratory Lasers and Spectroscopies of the University of Namur, with the help of a diode-laser spectrometer and, in the Center of Microsystems and Photonics of the University of Strathclyde of Glasgow, with the help of a difference frequency generation (DFG) spectrometer. The spectral parameters have been deduced from individual fits of theoretical lineshape models on the experimental profiles of each line at each pressure and at each temperatures. Various theoretical models were used taking into account Doppler and collisional broadenings, but also fine effects as the Dicke narrowing and the speed dependence effect. A lot of these results are totally originals. However, as soon as it was possible we compared our results with the p, L’objectif de cette thèse était d'étudier les paramètres collisionnels de raies d’absorption infrarouge de différents hydrocarbures, tels que l'éthane, l'allène et le méthane, depuis les basses jusqu'aux hautes températures. La détermination des profils verticaux de concentrations d’espèces en trace dans l'atmosphère et l'étude des gaz résiduels de combustion nécessitent la connaissance précise des paramètres spectraux de raies d'absorption, en particulier les coefficients d'élargissement collisionnel, sur une large gamme de température. Dans ce contexte, nous avons étudié différents mélanges gazeux présentant un grand intérêt pour l'étude de notre atmosphère ainsi que celle de Titan. Afin de mesurer ces paramètres à des températures supérieures à la température ambiante, nous avons, dans un premier temps, conçu, développé et mis au point une cellule d'absorption "haute température" permettant l'étude spectroscopique de profils de raies et de paramètres collisionnels de molécules en phase gazeuse entre 300 et 750 K. A l'aide de ce nouveau dispositif et de cellules d'absorption basse température développées précédemment au Laboratoire Lasers et Spectroscopies de l'Université de Namur, nous avons mesuré les coefficients d'élargissement collisionnel de raies d'absorption infrarouge d'hydrocarbures ainsi que leurs dépendances vis-à-vis de la température. Neuf mélanges gazeux ont été étudiés : éthane (C2H6−O2, C2H6−air), allène (C3H4−C3H4, C3H4−N2, C3H4−O2, C3H4−air) et méthane (CH4−N2, CH4−O2 et CH4−air). Les spectres ont été enregistrés au Laboratoire Lasers et Spectroscopies, à l'aide d'un spectromètre diode-laser accordable en fréquence et, au Centre of Microsystems and Photonics de l’Université de Strathclyde de Glasgow, à l'aide d'un spectromètre à génération par différence de fréquence. Les paramètres spectraux ont été déterminés en ajustant de manière individuelle un profil théorique sur le profil expérimental et ce, pour chaque raie à chaque pression et à chaq, (DOCSC01) -- FUNDP, 2013

LSDs (Lysosomal storage diseases) represent diverse sets of conditions resulting from an impaired uptake, sorting or digestion of the material captured by cells during endocytosis or autophagy. These autosomal recessive diseases can be caused by defects in soluble enzymes, in non-enzymatic lysosomal proteins or even in non-lysosomal proteins, resulting, in fine, to the storage of specific macromolecules inside the organelles of the endo-lysosomal system. Numerous and complex biochemical and signaling cascades have been shown to be activated/altered in response to the original lysosomal disorder and are now known or suspected to play an essential role in the cell dysfunction and death. Such “pathogenic mechanisms” include, for example: alterations of cellular calcium homeostasis and impairment of autophagy, the onset of oxidative stress and inflammation (and autoimmune response), an endoplasmic reticulum stress response as well as changes in the lipid homeostasis and mitochondrial dysfunction. However, even if changes in mitochondrial morphology have been already described in more than ten LSDs, the molecular mechanisms underlying these defects in response to the lysosomal storage and more generally the impact of lysosomal dysfunction on mitochondria remain poorly characterized. The first part of this work has been dedicated to the study of the effect of the TPP-1 (TriPeptidyl-Peptidase-I) deficiency (a lysosomal hydrolase deficient in the LINCL (Late Infantile Neuronal Ceroid Lipofuscinosis)) on the mitochondrial population of human skin fibroblasts. We found that a TPP-1 deficiency induces a fragmentation of the mitochondrial network in these cells, probably caused by a reduction in the abundance of both Mitofusin 1 and Mitofusin 2, two proteins that are essential for the mitochondrial fusion process. Surprisingly, this aberrant mitochondrial morphology is not accompanied by changes either in the matrix calcium concentration or in the abundance of ROS (Reactive Oxy, (DOCSC03) -- FUNDP, 2013

Since the beginning of the 1980s, stocks of European eel have been declining in most of their geographical distribution area. Many factors can be attributed to this decline such as pollution by xenobiotics released into the environment through agricultural, industrial and domestic activities. Because the New European Chemicals Legislation (REACh) is asking for alternatives to animal testing and reduction of animals sacrified in ecotoxicology and in accordance with conservation biology considerations, we have developed an appropriate and reproducible methodology to obtain a post-nuclear fraction of isolated European eel peripheral blood mononuclear cells (PBMC) in order to evaluate the toxicity of xenobiotics using a subproteomic approach. In a first study, we have studied the in vitro toxicity of perfluorooctane sulfonate (PFOS) in eel PBMC exposed during 48 h to sublethal concentrations (10 µg and 1 mg PFOS/L). A proteomic analysis using 2D-DIGE was performed to compare PBMC from the control group with cells exposed to the pollutant. A total of 48 proteins displaying significant changes in abundance were identified and categorized according to their functional classes. Besides providing clues on the cellular pathways mainly affected by PFOS, results allowed the identification of proteins rarely found in other ecotoxicological proteomic studies. These proteins could constitute potential biomarkers of exposure to PFOS in fish. In order to determine the specificity of the proteomic pattern observed after in vitro PFOS contaminations, we have completed the set of data with in vitro exposures to two other xenobiotics, dichlorodiphenyl-trichloroethane (DDT) and cadmium, using exactly the same methodologies as for the PFOS experiments. The aim of this new study was the discovery of protein expression signatures specific of different classes of pollutants. The identification of the proteins of interest by mass spectrometry allowed selecting four candidates for a minimal co, (DOCSC03) -- FUNDP, 2013

Since their first use, solid-state lighting devices have received a growing interest and popularity from engineers, physicists, industry and consumers. Their promising internal efficiencies, i.e. the high conversion rates of injected current to produced light, make them very appealing for the replacement of incandescent or fluorescent light sources. The major challenge for the development of these light sources is to enhance the external light extraction: the active material of light emitting diodes is in general a semiconductor with a high refractive index, which considerably limits the extraction of light into free space due to total reflection. This lack of high external efficiency has generated an important amount of research and publications. Very different approaches have been considered to enhance the external light extraction efficiency: photonic crystals, photonic structures inside and above the active material, graded refractive index layer to reduce the high index contrast between the active material and air, plasmonic resonances and more. In the present research, the bioluminescent organ's morphology of a Panamanian firefly is used as a source of inspiration to improve the light extraction efficiency of light-emitting devices. The internal efficiencies of light-emitting devices are nowadays very high, yet, the overall efficiency is limited by the total internal reflection due to the high refractive index of the incident medium. Fireflies emit light in their dense bioluminescent organ and light extraction is equally limited by total internal reflection. During their million years of evolution, the bioluminescent organ had the time to improve both, its internal functioning and its light extraction efficiency. The thorough analysis of the lantern's morphology shows several structures added on the light path, that could influence the light extraction efficiency. The jagged scales form a micrometric, two-dimensional and asymmetric structure which is shown, th, Les diodes électroluminescentes ont reçu un intérêt croissant de la part des ingénieurs, physiciens, industriels et consommateurs, depuis leur première utilisation. Leur efficacité interne élevée, c'est-à-dire le taux de conversion élevé de courant injecté en lumière émise, les place en bonne position pour remplacer les sources lumineuses incandescentes et fluorescentes. Une limitation persiste néanmoins sur l'efficacité globale de la diode: les matériaux actifs ont des indices de réfraction élevés par rapport au milieu émergent (l'air), ce qui limite considérablement l'extraction de lumière, et ainsi l'efficacité externe, à cause du phénomène de réflexion totale. Ce manque d'efficacité externe a généré une activité de recherche considérable avec une grande variété d'approches différentes pour résoudre le problème: cristaux photoniques, structures photoniques dans et au dessus du milieu actif, couches d'indice de réfraction adaptative pour réduire le contraste élevé entre le milieu incident et émergent. L'organe bioluminescent d'une luciole du Panama est utilisé comme source d'inspiration pour l'amélioration de l'efficacité d'extraction de lumière des diodes dans la recherche présentée dans ce manuscrit. La lumière émise par les lucioles est générée chimiquement dans son organe bioluminescent, qui présente un matériau dense par rapport à milieu émergent (l'air). Pendant les millions d'années d'évolution, l'organe bioluminescent a pu avoir le temps d'améliorer son fonctionnement interne ainsi que l'extraction de lumière, c'est-à-dire son efficacité externe. L'étude morphologique de la lanterne a montré différentes structures qui peuvent influencer la propagation de la lumière entre l'organe émetteur et l'air libre. Les écailles inclinées forment un réseau micrométrique, bidimensionnel et asymétrique. Les simulations associées montrent que cette structure augmente considérablement l'extraction de lumière. Une analyse similaire est conduite pour deux modèles inspirées, (DOCSC01) -- FUNDP, 2013

In western countries, human concern for stress, welfare and health of livestock is growing up. In aquaculture, stress reduction is important from an ethical point of view but also results in an increased fish welfare and productivity. Stress response is quite complex phenomenon including release of several hormones. The most studied hormone during stress response in teleosts is cortisol, also called stress hormone. It is the most important corticosteroid in fish, modulating a vast range of physiological processes including general metabolism, growth, reproduction and immunity. Pathogen outbreaks are frequently reported in fish husbandry. Stress resulting from husbandry is suspected to favour these pathogen outbreaks. Furthermore, cortisol is reported to modulate all levels of the immune system; both cellular and humoral immune defences involved in both innate and adaptive immune systems. Most of the functions of corticosteroids are mediated through nuclear receptors called corticosteroid receptors. There are two types of corticosteroid receptors in teleosts as well as in mammals; the gluco- (GR) and mineralocorticoid receptor (MR). In mammals, as well as in teleosts, a bi-directional communication is reported between corticotropic axis and immune system. This bi-directional communication is essential to maintain efficient responses of both immune system and corticotropic axis, preventing adverse effects of too high or too long responses of those systems. This communication is well described in mammals, but several differences are reported between teleosts and mammals regarding corticotropic axis. Indeed, the mammalian mineralocorticoid aldosterone is not present at relevant physiological levels in teleosts. In 2005, 11-deoxycorticosterone (DOC) was identified to bind to and activate the mineralocorticoid receptor in several teleost species. This opens the door for a new putative active corticosteroid in teleosts. Furthermore, corticosteroid receptor diversity is hig, (DOCSC03) -- FUNDP, 2013

Le concept de défense au Cameroun, depuis 1960, est impulsé par une culture stratégique métissée. La thèse saisit la trajectoire de formation de cette culture stratégique et sa constellation pratique pour répondre aux exigences de l'environnement des menaces., (DOCSESG02) -- FUNDP, 2013

A huge amount of space debris are currently orbiting the Earth. Understanding the motion of such uncontrolled objects is of great importance in order to reduce the risks of hypervelocity impacts with manned and unmanned spacecraft. In this work, we present an accurate symplectic integration scheme to numerically propagate space debris orbits over long periods of time. Among the perturbations that influence debris motion, this thesis mainly brings new results about the effects of solar radiation pressure on debris characterized by high area-to-mass ratios. In this case, Earth’s shadow crossings cannot be neglected. Hence we propose an innovative method that successfully models shadow crossings and does not break the symplectic properties of our propagator. Both cylindrical and conical shadows are considered. We show that the cylindrical model is only a poor approximation of the more realistic conical model, especially for high area-to-mass ratios. Thanks to both numerical and semi-analytical techniques, we then explain how shadow crossings are responsible for large periodic deviations from the initial condition. Finally an analysis is presented to highlight the strong influence of shadow crossings on the stability of high area-to-mass space debris located around the geostationary altitude., De très nombreux débris spatiaux sont actuellement en orbite autour de la Terre. Le risque permanent de collisions entre ces objets incontrôlables et les sondes spatiales actives (habitées ou non) requiert la connaissance précise de leur trajectoire. Cette thèse propose un intégrateur symplectique permettant de propager numériquement et rapidement les orbites des débris sur de longs intervalles de temps. Les perturbations agissant sur leurs trajectoires sont nombreuses. En particulier, la pression de radiation solaire devient prédominante pour les objets dont le rapport surface sur masse est important. Les passages dans l’ombre de la Terre ne peuvent alors plus être négligés. Ce travail présente une méthode innovante de modélisation de ces passages dans l’ombre (cylindrique ou conique) dont la formulation permet de conserver le caractère symplectique du propagateur. Les résultats prouvent qu’une ombre cylindrique représente une mauvaise approximation de la réalité, et préconisent une formulation conique, particulièrement pour les grands rapports surface sur masse. Des méthodes numérique et semi-analytique sont ensuite développées pour expliquer les importantes déviations périodiques (observées sur les orbites) provoquées par ces passages dans l’ombre, avec des périodes allant de 1 à 10000 ans. Enfin, une étude systématique de la stabilité autour de l’altitude géostationnaire prouve la présence de chaos, dont l’intensité et l’étendue sont renforcées par les passages dans l’ombre., (DOCSC00) -- FUNDP, 2013

Financial deepening, especially through the microfinance revolution, has been one of the boldest and most promising global evolutions over the last decades. My thesis aims at building up the knowledge about the direct and indirect impacts of finance at the micro level, and especially about the mechanisms and welfare implications thereof. My thesis consists of three chapters. The first one focuses on the potential spillover effects that the entry of microfinance institutions can generate at the level of local informal credit markets. Using a standard model of lending in presence of adverse selection, I show that MFIs can trigger an increase in the equilibrium interest rate of the informal market. Using data from Indian villages, I provide supporting evidence fro the main predictions of the model. The second chapter investigates the impact of microfinance participation in India on educational outcomes. It is based on a unique long-term panel database on members of informal credit and saving associations, known as SHGs, in villages of Jharkhand, India, in which households were interviewed every two years between 2002 and 2009. Combining panel and propensity-score matching techniques, we find that members of SHGs are significantly more likely to enroll their children in school. However, the treatment effects take time to materialize (about five years on average) and are essentially concentrated on girls. The final chapter looks at the insurance aspect of SHGs. Using the same database as in chapter 2 combined with meteorological data, I study the extent and the nature of the reaction to rainfall shocks of rural households with and without access to microcredit. I find that member households enjoy a stable access to credit, opening the possibility of short-term consumption smoothing following an adverse rain shock., (DOCSESG00) -- FUNDP, 2013

Cocrystallization is a well-known method, which appears in specialized literacy since more than a hundred years but is highlighted since the last ten years to improve physico-chemical properties of target pharmaceutical compounds during development process. Despite the semantic lack of consensus about the real definition of what a cocrystal truly is, several categories of assemblies – ionic or zwitterionic, as studied in this work - could emerge from the nature itself of the cocrystallizing agent, or partners engaged in the cocrystal (also called coformers). The main goal of this work is to in-depth analyze several cocrystals implying amino acids, and more specifically Proline. This particular amino acid has been chosen for different reasons. First, its rigid structure, due to the presence of a 5-membered cycle, is an important advantage. This latter could also be considered as an elementary pattern in pharmaceutical compounds. On another hand, Proline possesses the highest water solubility among classical amino acids. With this aim in mind, several formation techniques are employed, the principal being mechanochemistry or (Liquid-Assisted) grinding. X-ray diffraction allows to analyze in details cocrystal structure, and to observe common organization patterns, or supramolecular synthons. Calorimetry techniques, and more particularly differential scanning calorimetry or thermogravimetric analysis, permit to characterize the thermal or the solubilizing behavior of the compounds formed via establishment of binary melting or ternary phase diagrams. A panel of other spectroscopic methods (also NMR, elementary analysis, HPLC) allows collecting information on the compounds, to eventually obtain the quantitative solubility of the cocrystals of API formed. Proline cocrystals, classified as ionic with MnCl2, zwitterionic with fumaric acid - a classical coformer in cocrystallization - or with naproxen, a marketed API from profen family, are characterized along this work. A so, La cocristallisation, ou formation de cocristaux, est une méthode connue depuis plus d’un siècle mais de plus en plus utilisée ces dix dernières années afin d’améliorer les propriétés physico-chimiques à l’état solide de molécules-cibles en cours de développement pharmaceutique. Malgré le débat sémantique qui agite encore la communauté scientifique, une définition claire du terme « cocristal » se dégage. Dans cette définition, plusieurs catégories d’assemblages se distinguent. Les cocristaux de type zwittérioniques ou ioniques, différenciés par la nature du partenaire (agent) de cocristallisation (ou coformère), sont principalement étudiés dans ce travail. L’objectif majeur de cette thèse est de réaliser une étude de cas fouillée de cocristaux faisant intervenir des acides aminés et plus particulièrement la Proline. Celle-ci a été sélectionnée pour plusieurs raisons : sa structure impliquant un cycle à cinq pièces (dont un azote), unique parmi les acides aminés classiques, lui confère une plus grande rigidité. Son noyau cyclique est donc représentatif d’un modèle de base de molécules pharmaceutiques. Sa solubilité dans l’eau est la plus élevée des acides aminés classiques. Différentes techniques de formation de cocristaux de proline sont utilisées, dont la principale est la mécanochimie ou broyage (à sec ou humide) des précurseurs. La diffraction de rayons X nous permet d’analyser en profondeur la structure moléculaire des cocristaux formés et de dégager des motifs communs d’organisation, ou synthons supramoléculaires. Différentes techniques calorimétriques, telles que la calorimétrie différentielle à balayage ou l’analyse thermogravimétrique, permettent d’étudier le comportement thermique global des composés formés, par le biais de l’édification de diagrammes binaires. Deux autres techniques d’investigation innovantes utilisées lors de séjours au sein du laboratoire SMS de l’Université de Rouen (Prof. Gérard Coquerel) renseignent sur la solubilisation dans un solva, (DOCSC02) -- FUNDP, 2013

x, (DOCSESG00) -- FUNDP, 2013

Particle accelerators are technological devices which allow studies at both infinitely small scale, e.g. particles responsible for elementary forces, and extremely large scale, e.g. the origin of cosmos. This work is concerned with area-preserving maps modelling ring accelerators. We prove a theorem on control allowing us to build two new maps. These systems exhibit excellent dynamical properties : wider dynamical aperture, reduction of chaos and a reduced frequency space. The results have a strong analitical basis and are validated numerically with the normal form theory (NF), the chaos indicator SALI and the frequency map analysis (FMA). Finally we present a very new direction in the control of dynamical systems : controlling dissipative systems that are perturbations of integrable ones. We give a detailed presentation of the first theoretical and numerical results through the van der Pol model., (DOCSC00) -- FUNDP, 2013

Over the last decade, tremendous research has been focused on the synthesis and applications of hierarchically porous materials. Hierarchical porous materials have enhanced materials’ properties compared to those with unimodal pore structure. Owing to their structure, a large series of domains have a fervent interest in hierarchically porous materials. This thesis is aimed at designing a new reaction system to develop hierarchically porous metal alkoxides with novel porosities via a spontaneous self-formation procedure. Furthermore, this thesis is also aimed at investigating the possible formation mechanism based on the self-formation procedure, and also the photocatalytic performance and adsorption capacity of the hierarchically porous metal alkoxides. The objective of this thesis is to fabricate a series of hierarchically porous materials with different porosities by adjusting the spontaneous self-formation procedure from metal alkoxides via novel strategies. In this thesis, we developed a novel water-adjusting method in order to adjust the amount of water in the reaction system thus controlling the self-formation procedure. Acetonitrile and methanol were used as the examples to be the reaction mediums here. On the basis of this novel strategies, a series of metal oxides with diverse porous structures had been synthesized, which would be suitable for a variety of applications from catalysis, to separation or environmental remediation. The evolution of the porosity of textural properties of metal oxides, formed from the addition of metal alkoxide to a water-acetonitrile system, with increasing water content was carefully investigated and summarized. The formation mechanism of hierarchically porous metal oxides in a water-acetonitrile system had been discussed in detail. Furthermore, the spontaneous self-formation process to form hierarchically porous titania in methanol was also studied in this thesis. More importantly, the hierarchically 3D dendrimeric nanostructu, (DOCSC02) -- FUNDP, 2013

L’administration est aujourd’hui profondément transformée par la technologie. C’est séduisant, mais également dangereux. Outre la crainte de Big brother, naît celle d’une administration kafkaïenne c’est–à-dire une administration à ce point technique et complexe qu’elle en devient incompréhensible et donc incontrôlable. Comment faire pour que le citoyen ne soit pas exclu de cette évolution numérique ? Cet ouvrage démontre qu’il est possible d’organiser un e-gouvernement efficace tout en garantissant au citoyen les moyens nécessaires pour garder une prise sur l’administration, afin de la comprendre et de la contrôler. Cela passe par une modification en profondeur du droit administratif, afin de l’enrichir et de le moderniser grâce au régime juridique de la protection de la vie privée et des données à caractère personnel. La recherche est structurée à partir de trois piliers de l’État de droit ébranlés par l’e-gouvernement : la légalité, la transparence et le contrôle. Pour chacune de ces exigences, l’auteur montre qu’il est possible de greffer les règles de protection des données sur les règles de droit administratif, afin de dégager une cohérence dans les règles applicables à l’e-gouvernement. Elle montre également qu’il faut aller plus loin et dégager de nouvelles solutions, juridiques et technologiques, pour répondre aux dangers de l’e-gouvernement. Cet ouvrage donne au droit administratif une dimension nouvelle à l’heure de l’e-gouvernement, qui doit désormais être connue, enseignée et pratiquée., (DOCJURI00) -- FUNDP, 2013

Identifying transcriptional regulators of a gene of interest often represents a time- and work-consuming task, as currently used in silico analyses of DNA regulatory sequences are often disappointing, generating a lot of false positive and false negative candidates for further experimental validations. For these reasons, mass spectrometry-based identification of proteins captured by DNA-affinity methods have emerged these last years. However, these methods are challenging as they have to cope with the relatively low abundance of transcriptional regulators embedded in complex mixtures of highly expressed unspecific trapped proteins. Consequently, these methods are generally conducted with short DNA sequences by comparing proteins captured by a wild-type probe to the interactions detected with a mutated binding site. Although powerful, these approaches cannot be qualified as without “a priori” as they require pre-existing knowledge of the binding site of interest. In this work, we developped a straightforward procedure to detect, without “a priori”, a large panel of proteins interacting with a relatively long DNA sequence. As a proof of concept, a 226 bp-long sequence of the HIV-1 5’LTR promoter sequence was used as a bait, as this sequence is particularly well known and rich in transcription factor binding sites. The identification of NFB members among the interacting proteins was first used as a read out to set up the different parameters of the technique. This approach was then used to identify more than sixty proteins related to transcription, including 24 transcription factors and 38 transcriptional coregulators that interact indirectly with the DNA sequence. The presence of several transcription factors known to regulate the transcription of HIV-1 validated the technique, while the identification of 12 other transcription factors not previously described to be involved in the context of HIV-1 regulation underlines the advantage to conduct without “a priori” ana, (DOCSC03) -- FUNDP, 2013

Tuberculosis, caused by Mycobacterium tuberculosis (TB), one of the most contagious diseases, threatens the world population because of the emergence of pathogenic strains highly resistant to known antibiotics. UDP-Galactopyranose mutase (UGM) is a validated target for the discovery of new therapeutic agents to fight TB. This enzyme can catalyze the interconversion of UDP-Galactopyranose (UDP-Galp) into UDPGalactofuranose (UDP-Galf). The contribution of UGM in the biosynthesis of Galf containing glycoconjugates and its absence in mammals push the community to synthesize novel inhibitors in order to elucidate the modes of action and binding of this enzyme. The design of new mechanistic probes that mimick UDP-Galf or the transition states of this reaction will help to better understand its mechanism and then may allow the development of new drugs to cure TB. The aim of this thesis is to synthesize a series of UDP-carbasugars analogues of UDP-Galf in order to study the mechanism and the binding properties of UGM. These compounds feature a UDP moiety, a galactitol chain for mimicking high-energy intermediates of the enzymatic reaction. All these characteristics are essential for the binding within the active site of UGM. Cyclohexene derivatives could be obtained by ring-closing metathesis from the corresponding diene which would be generated by a multi-step synthesis starting from D-galactose. Two different categories of UDP-Galf analogues have been synthesized using the carbocycle (cyclohexene) as precursor: compounds with a phosphonate moiety or with a phosphate group. From these two scaffolds, a divergent synthesis has been carried out by functionalizing the double bond of the carbocycle. These products have then been coupled with uridine monophosphate to provide the different UDPcarbasugars. The inhibition profile of UDP-carbasugars showed that these compounds are competitive inhibitors of UGM. UDP-cyclohexene and UDP-cyclohexane provides the best inhibition profile, (DOCSC02) -- FUNDP, 2013

The striped catfish (Pangasianodon hypophthalmus) farming system in the Mekong Delta of Viet Nam has been vigorously developed in recent years. It has resulted from expansion of farming areas, application of new farming techniques and an increase of intensification level. As in other developing striped catfish culture venture, health problems including disease outbreaks have been encountered. The use of chemicals and antibiotics in striped catfish farming has increased for prevention and treatment of diseases. These compounds have attracted criticism because of a potential hazard for fish health, environment risk and human consumers. The present study aimed to evaluate the efficiency of different immunostimulating compounds in striped catfish farming in order to reduce the use and impact of antibiotics and chemicals by alternative method of immunostimulation. A combination of in vitro and in vivo approaches was used to investigate the effects of Lipopolysaccharide (LPS) on immune responses of striped catfish. Some potential results of this research were highlighted. The innate immune system of striped catfish was significantly stimulated by LPS injection or feeding through the increase of respiratory burst, lysozyme and complement activities. Total of immunoglobulins was also enhanced in LPS treatment. A challenge test with a common bacterial pathogen (Edwardsiella ictaluri) for striped catfish was performed and documented that LPS could significantly reduce the cumulative mortality of fish, especially in low dose such as 3 mg LPS/kg fish for injection and 0.01% of LPS for oral. Proteomic analysis performed in both approaches suggested that LPS could stimulate the over-expression of several immune proteins such as complement component, lysozyme precursor, transferrin, immunoglobulin,… In addition, the results from in vitro also showed that the response of striped catfish to LPS involved an increase of many protein expression related in cytoskeleton, stress response, (DOCSC03) -- FUNDP, 2013

The bacterial cell cycle is a developmental process starting with newborn bacteria that progress to the predivisional status in which they eventually generate two daughter cells. Along their development, the newborns grow and replicate their genome that is in turn faithfully transmitted to the two siblings. The bacterial cell cycle has been extensively investigated in the alphaproteobacterium Caulobacter crescentus, which produces a small non-replicating (G1 phase) swarmer cell for the colonization of new niches in aquatic environments at each cell division. The pathogen Brucella abortus is also part of the alphaproteobacteria group but displays a singular cell cycle compared to C. crescentus. Opposite to C. crescentus, B. abortus growth mode is unipolar resulting in the asymmetric distribution of the cell wall material in the predivisionnal cell. This asymmetry is further exacerbated by an asymmetric division that generates a large cell composed of “old” cell wall material and a small cell made of a new envelope material. In addition, B. abortus also contains a genome divided into several replicons each encoding its own segregating apparatus. Among those replicons is included a chromid (a combination of chromosomal and plasmidic features) carrying a RepAB-based segregation system for which the localization has not been not assessed so far. During this PhD thesis, we characterized the mechanisms of unipolar growth and chromosomes segregation of B. abortus. Concerning the unipolar growth study, we localized the only monofunctional transpeptidase penicillin-binding protein (FtsI) identified in B. abortus that creates links between the different peptidoglycan strands at every growth zone. The localization of FtsI revealed that this protein is present at the growing pole during the unipolar elongation and at the constriction site during the division. These data suggest the presence of a unique growth machinery performing both the elongation (at the new pole) and the div, (DOCSC03) -- FUNDP, 2013

Tuberculosis remains a major threat in the world; in 2012, 8.6 million new TB cases were found. After the human immunodeficiency virus (HIV), TB has been considered as one of the most infectious diseases in history and the second leading cause of death. Effective drugs treatments are known and have been used since 1960. New TB drugs have been tested in clinical trials. However, the appearance of multidrug resistant strains has urged the research for finding new therapeutic agents to cure tuberculosis. Among the different enzymes involved in the formation of the mycobacterial cell wall, UDP-Galactopyranose mutase (UGM) was identified as a new target. Indeed, this enzyme allows a peculiar reaction: the contraction of the cycle of UDP-Galp into UDP-Galf. This thesis was based on the identification of novel potential inhibitors of UGM in order to understand the mechanism of this enzyme. The enzymatic studies were performed on two different categories of molecules: UDP-F4-Galactose and natural products. In the first part of this project, we synthesized polyfluorinated sugars, UDP-F4-Galactose, as analogues of the natural substrate UDP-Galactofuranose. Thus, four fluorine atoms were introduced at 2 and 3 positions of the galactose. Then, biochemical assays of these molecules were carried out on UGM. The inhibition study allowed us to determine the binding affinity present between the UDP-F4-Galactose and the enzyme. The second part reported the screening of a small library of natural compounds which lead to identify new potential inhibitors of UGM. Biochemical assays and molecular modeling studies have been performed on these molecules to better understand the interactions between these compounds and UGM within the active site., (DOCSC02) -- FUNDP, 2013

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Cancer cell resistance against chemotherapy is still a heavy burden to improve anticancer treatments. Understanding the mechanisms responsible for the resistance against chemotherapy-induced cell death is of interest since the number of patients with cancer increases and relapse is commonly observed. Development of hypoxic regions is known to promote cancer cell adaptation to the stressful tumoral microenvironment and resistance against anti-cancer therapies. The HIF-1 signaling pathway, activated under hypoxia, promotes cancer cell adaptation and resistance against chemotherapy. Other biological processes are also activated under hypoxia and/or after chemotherapy treatment and are known to promote cancer cell survival. Autophagy and UPR (unfolded protein response) are part of these processes. Therefore, during the first part of this work, we sought to evaluate the role of autophagy and hypoxia on the taxol-induced apoptosis in MDA-MB-231 breast cancer cells. Results showed that taxol induced apoptosis after 16 h of incubation, and that hypoxia protected MDA-MB- 231 cells from taxol-induced apoptosis. In parallel, taxol induced autophagy activation already after 2 h of incubation both under normoxia and hypoxia. Autophagy activation during taxol exposure was shown to be a protective mechanism against taxol-induced cell death both under normoxia and hypoxia. However, at longer incubation times, the autophagic process reached a saturation point under normoxia leading to cell death, whereas under hypoxia, autophagy flow still correctly took place allowing the cells to survive. Autophagy induction was initiated via mechanistic target of rapamycin (mTOR) inhibition, which is more important in cells exposed to hypoxia. Taxol also induced c-Jun N-terminal kinase (JNK) activation and phosphorylation of its substrates B-cell CLL/lymphoma 2 (Bcl2) and Bcl2-like 1 (BclXL) under normoxia and hypoxia very early after taxol exposure. Bcl2 and BclXL phosphorylation was decreased m, La résistance des cellules cancéreuses à la chimiothérapie est un problème crucial pour améliorer les traitements anticancéreux. La compréhension des mécanismes responsables de la résistance à la mort cellulaire induite par la chimiothérapie est toujours d’actualité car le nombre de patients atteints d’un cancer ne cesse d’augmenter et des rechutes sont souvent observées. Le développement de régions hypoxiques au sein des tumeurs est connu pour favoriser l’adaptation des cellules cancéreuses à leur environnement stressant et la résistance aux thérapies anticancéreuses. Les voies de signalisation dépendantes de HIF-1 (hypoxiainducible factor-1), qui sont activées en hypoxie, favorisent l’adaptation des cellules cancéreuses et la résistance à la chimiothérapie. D’autres processus biologiques, activés en hypoxie et/ou suite à un traitement chimiothérapeutique, sont également connus pour favoriser la survie des cellules cancéreuses. L’autophagie et l’UPR font partie de ces processus biologiques. Pour cette raison, durant la première partie de ce travail, nous avons étudié le rôle de l’autophagie et de l’hypoxie dans l’apoptose induite par le taxol dans les cellules MDA-MB- 231 issues d’un cancer du sein triple négatif. Les résultats montrent que le taxol induit l’apoptose après 16 heures d’incubation et que l’hypoxie protège les cellules MDA-MB-231 de l’apoptose induite par le taxol. En parallèle, le taxol induit l’activation de l’autophagie après 2 heures d’incubation en normoxie et en hypoxie. L’activation de l’autophagie dans les cellules incubées avec du taxol est un mécanisme protecteur contre l’apoptose induite par le taxol en normoxie et en hypoxie. Cependant, après des temps d’incubation plus longs, le processus autophagique atteint un seuil de saturation en normoxie, conduisant à la mort cellulaire. En hypoxie, le flux autophagique se déroule correctement même après des temps d’incubation plus longs, ce qui permet aux cellules de survivre. L’autophagie est acti, (DOCSC03) -- FUNDP, 2013

Over the past few decades, one principle research area has focused on the quantification of toxic heavy metals within the organism, the environment and in industrial waste. Amongst these metals, mercury is considered as one of the most harmful due to its devastating effects on the environment and human health. To minimize the dramatic consequences of this highly toxic metal, it seems essential and urgent to design a novel fluorescent detection method to monitor Hg2+ ions based on highly sensitive and selective, fast, miniturisable, reusable and also portable optical devices which can be used to perform field measurements in-situ. Therefore, this thesis project aims at designing optical nanosensors based on fluoroionophores immobilised within mesoporous silica matrices for the detection of Hg2+ ions. To achieve the aim of this project, different fluorescent probe molecules (fluoroionophores), each responding by an enhancement in fluorescence intensity after complexation with Hg2+ ions (due to the modification of their photophysical properties), have been successfully synthesised and tested for their ability to quantify Hg2+ ions with sensitivity and selectivity. The optimisation phase of the molecular structure of the fluoroionophore revealed to be fundamental not only in order to reinforce the interaction (sensitivity and selectivity) between the ion and the recognition site of the fluorescent molecule but also to fill the immobilisation conditions of the probe molecule onto the porous support. To do this, structural changes have been made to both the chelating part (ionophore) and the fluorescent part (fluorophore) of the molecule. Sulfur and selenium have been selected as chelating atoms to the Hg2+ ion and thus incorporated into the ionophore structure and withdrawing groups (bromine and methyl ester) have been grafted onto the fluorophore, the anthracene. Through this study, it was shown that sulfur based ionophores complexed with sensitivity and selectivity bot, Durant ces dernières décennies, une des principales thématiques de recherche s’est focalisée sur la détection et le dosage des métaux lourds présents dans l’organisme, l’environnement ou encore dans les déchets industriels. Parmi ces métaux lourds nuisibles, le mercure occupe une place importante de par ses effets dévastateurs tant sur l’environnement que sur la santé de l’Homme. Dans l’optique de limiter au maximum les conséquences dramatiques de ce métal hautement toxique, il apparaît capital et urgent de développer une nouvelle méthode de détection de ces ions métalliques basée sur un système optique hautement sensible et sélectif, rapide, miniaturisable, réutilisable mais encore portable permettant, ainsi, la prise de mesures directement sur le terrain. De ce fait, ce projet de thèse proposait la conception de nanosenseurs optiques du type fluoroionophores immobilisés au sein de matrices silicées mésoporeuses pour le dosage des ions Hg2+. Afin de mener à bien ce projet, différentes nouvelles molécules sondes fluorescentes (fluoroionophores) répondant toutes par un renforcement de l’intensité de fluorescence linéaire après complexation avec l’ion Hg2+ (dû à la modification de leurs propriétés photophysiques) ont été synthétisées avec succès et testées au niveau de leurs aptitudes à doser sensiblement et sélectivement les ions Hg2+. En outre, un travail d’optimisation de la structure moléculaire du fluoroionophore s’est confirmé être fondamental en vue de renforcer l’interaction (sensibilité et sélectivité) entre l’ion et le site de reconnaissance de la molécule fluorescente mais également pour satisfaire aux conditions d’immobilisation de la molécule sonde sur le support poreux. Pour ce faire, des modifications structurales ont été apportées tant à la partie chélatante (ionophore) qu’à la partie fluorescente (fluorophore). Ainsi, le soufre et le sélénium ont été sélectionnés en tant qu’atomes complexants à l’ion Hg2+ au sein de la structure de l’ionophore et des, (DOCSC02) -- FUNDP, 2013

The present thesis provides a critique of the categories underpinning the European Commission’s immigration policy, foregrounding the limitations and exclusionary effects of those categories. It advances that the study of categories, which are always socially constructed, is central for understanding that policy and its detrimental effects, and for eventually transforming or modifying it. The analysis draws on Wittgenstein’s theory of language games as a social practice which shapes both thought and activity, the cognitive psychologists who have used that theory to think through the mental process of categorisation, the social psychologists who situated categorisation at the heart of intergroup processes and exclusion, and also Foucault’s theory of discourse as embedded in power relations and regimes of truth. The thesis appraises each of these approaches: it opens by exploring the different schools of thought on categorization from the realist conception of categories as a reflection of existing social objectivity, which the thesis rejects, to the Foucauldian approach which stresses the radical contingency of any meaningful organisation of the world. A new, integrated multidisciplinary method of policy analysis is then designed that draws on these various schools of thought. The thesis then proceeds to apply this framework to the case study of the European Commission’s immigration policy (1999-2012), arguing that the categories which inform that policy are driven by the broader life form or truth regime of neoliberal governmentality, defined by its market morality. This morality defines the categories of immigrants in terms of economic utility and profitability rather than social or moral need. The thesis aims to problematize this system of categorization by highlighting both at once its susceptibility to modification, its flexibility, and its resistance to change., (DOCSESG02) -- FUNDP, 2013

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The household is the basic economic unit and the nucleus of social relations in both developed and developing countries. Individual motivations to optimize one’s own behavior, as well as interactions between individuals within the household and especially within the couple are essential to achieve economic optimality. Another very important institution in developing countries is the extended family, seen as all the people linked by blood ties. Both the household and the enlarged family can be important sources of insurance and credit when formal financial markets are not working properly. Since family ties allow an easy flow of information and give the opportunity to implement strong social sanctions, the family is a privileged vector of financial transactions. To date, the majority of decision models within the household have either considered the household as a single decision-maker or made the hypothesis of the existence of an efficient bargaining process deriving from the possibility of a stable commitment between actors and of a perfect exchange of information. At the same time, there have been several empirical works showing that the hypothesis of Pareto optimality and complete insurance within households can typically be rejected: spouses do not always pool their income and individual consumption responds to individual income shocks, violating the hypothesis of full risk sharing. During my PhD, I personally conducted, in collaboration with Jean-Marie Baland, Isabelle Bonjean and Catherine Guirkinger, an extended household survey in the city of Bafoussam (West Cameroon), to study transfer within the household and the extended family. We recorded the choices of each adult in the households about consumption, savings, transfers and sharing of information. We observed that, in many households, the perception of other household members’ income is highly imperfect. I therefore decided to study theoretically the issues of cooperation and communication within the hou, (DOCSESG00) -- FUNDP, 2013

The aim of this manuscript is to present the results of the doctoral research project titled “Development of service innovation capabilities in knowledge-intensive organizations”. The rationale for carrying out the project was the disproportionately limited insight academics currently have into how knowledge intensive organisations develop and dynamise their service innovation capabilities, compared to the already very high and constantly growing importance of knowledge-intensive services in the developed economies. In order to explore this relatively under-investigated field, we have carried out six case studies in two groups of knowledge-intensive organisations – business consultancies and Research and Technology Organisations. Our work lays foundations for better understanding of the key service innovation capabilities building blocks, as well as related practices used by successful organisations. We also propose a set of concrete organisational capabilities identified as important for service innovation, namely (1) committing to service innovation, (2) spotting trends in the market, (3) partnering for service innovation, (4) dialoguing with (potential) clients, (5) inventing new service solutions (6) focusing organisational service innovation efforts, (7) locating required expertise, (8) integrating different skills and perspectives, (9) cultivating new service growth, (10) demonstrating new service value (11) leveraging organisational service experience and (12) de-contextualising developed services for future re-use. Finally, in an attempt to illustrate how organisations ensure the dynamisation of these capabilities in a continuous fashion in practice, we propose the following as drivers: (a) constant ‘flow’ or movement in the organisation, (b) continuous improvement philosophy, (c) regular ‘change of scenery’, (d) ‘pause and reflect’ time, (e) no-blame culture, (f) trust and openness, (g) open invitation of criticism and ideas, (h) outside-in perspective, (I), (DOCSESG00) -- FUNDP, 2013