Le potassium (K+) est impliqué dans la régulation de l’excitabilité cellulaire, la régulation du cycle cellulaire, la viabilité cellulaire, la neuroprotection et le maintien des fonctions microgliales et oligodendrocytaires. Le dysfonctionnement des canaux potassiques, décrit dans plusieurs maladies neurodégénératives comme la Maladie d’Alzheimer (MA), la sclérose en plaques (SEP), la maladie de Parkinson et la maladie de Huntington, pourrait être une potentiel cible thérapeutique. Les mécanismes toxiques sous-jacents de ces pathologies neurodégénératives impliquent des oxystérols, dérivés oxydés du cholestérol, et des acides gras en relation avec le métabolisme peroxysomal. Le 7-cétocholestérol (7KC), le 24S-hydroxycholestérol (24S-OHC) et l'acide tétracosanoïque (C24: 0), souvent trouvés à des taux élevés au niveau du cerveau et dans le plasma de patients atteints de maladies neurodégénératives (MA, maladie de Nieman-Pick, SEP, maladie de Parkinson, maladie de Huntington et X-ALD conduisent une rupture de l’équilibre Redox qui aboutirait à la neurodégénérescence. Dans ce contexte, il est intéressant de déterminer l’éventuelle connexion entre environnement lipidique et homéostasie potassique. L’étude in vitro a été réalisée sur des olygodendrocytes murins 158N et les cellules microgliale BV-2. Nous avons montré que la lipotoxicité du 7KC, 24S-OHC et C24:0 implique une rétention du K+ faisant intervenir les canaux potassium voltage dépendant (Kv). Ces résultats ont montré que l'inhibition des canaux Kv conduisant à une augmentation la [K+]i contribue à la cytotoxicité du 7KC, 24S-OHC et C24:0. Nous nous sommes focalisés sur le canal Kv3.1b. La retention du K+ induite par les oxystérols (7KC et 24S-OHC) serait sous le contrôle de Kv3.1b. L’étude clinique réalisée sur du plasma de MA a révélé une corrélation négative entre le taux d’acide docosahexaénoïque (DHA) et la concentration de K+. Chez les souris transgéniques J20, modèle de la MA, l’étude de la topographie d’expression de Kv3.1b et d’Abcd3, au niveau de l’hippocampe et du cortex, a montré une baisse de l’expression de ces deux marqueurs. Dans leur ensemble, les résultats obtenus ont établi des relations entre lipotoxicité, métabolisme peroxysomal et altération de l’homéostasie potassique dans la neurodégénérescence et suggèrent une possible modulation de l’expression et de l’activité de kv3.1b dans la physiopathologie des maladies neurodégénératives. / Potassium (K+) is involved in the regulation of cellular excitability, cell cycle regulation, cell viability, neuroprotection and maintenance of microglial and oligodendrocytic functions. Potassium dysfunction, described in several neurodegenerative diseases such as Alzheimer's Disease (AD), multiple sclerosis (MS), Parkinson's disease and Huntington's disease, may be a potential therapeutic target. The underlying toxic mechanisms of these neurodegenerative pathologies involve oxysterols, which are oxidized cholesterol derivatives, and fatty acids including those associated with peroxisomal metabolism. 7-ketocholesterol (7KC), 24S-hydroxycholesterol (24S-OHC) and tetracosanoic acid (C24:0), often found at increased levels in the brain and plasma of patients with neurodegenerative diseases (Nieman-Pick disease, MS, Parkinson's disease, Huntington's disease and X-ALD) lead to a breakdown of the redox equilibrium leading to neurodegeneration. In this context, it is interesting to determine the possible connection between the lipid environment and potassium homeostasis The in vitro study was carried out on 158N murine oligodendrocytes and microglial BV-2 cells. We have shown that the lipotoxicity of 7KC, 24S-OHC and C24:0 implies retention of K+ involving the voltage dependent potassium channels (Kv). These results have shown that inhibition of Kv channels lead to an increase in [K +] i contributing to the cytotoxicity of 7KC, 24S-OHC and C24:0. The retention of K+ induced by oxysterols (7KC and 24S-OHC) would be under the control of Kv3.1b. A clinical study, on plasma of patients with Alzheimer’s disease, revealed a negative correlation between docosahexaenoic acid (DHA) and K+ concentration. In the J20 mice, a transgenic model of Alzheimer’s disease, the expression of Kv3.1b and Abcd3 was decreased in the hippocampus and cortex. Overall, the results obtained established relationships between lipotoxicity, peroxisomal metabolism and potassium homeostasis in neurodegeneration and suggest a possible modulation of the expression and activity of kv3.1b in the pathophysiology of neurodegenerative diseases. So, modulation of Kv3.1 could constitute a new therapeuthic approach against some neurodegenerative diseases.

Die genaue physiologische Funktion des zellulären Prion-Proteins (PrPC) ist noch immer nicht vollständig verstanden. Eine mögliche Funktion des PrPC auf das neuronale Überleben nach einem hypoxischen oder ischämischen Insult wird diskutiert. In einem Vorversuch zeigten sich nach zerebraler Ischämie deutlich größere Infarktvolumina in den Gehirnen von Prion-Knock-Out-Mäusen im Vergleich zu denen der Wild-Typ-Mäuse. Das Identifizieren der molekularen Mechanismen der PrPC-vermittelten Neuroprotektion ist daher von großem Interesse und machte die Etablierung eines Zell-Modells erforderlich. Neuere Studien konnten einen Einfluss des zellulären Prion-Proteins auf die Glykolyse nachweisen. Unter Sauerstoffmangelbedingungen kommt es zu einer vermehrten Bildung von Laktat durch das Enzym Laktat-Dehydrogenase (LDH). Neurone benötigen unter hypoxischen oder ischämischen Bedingungen dieses Laktat als Energiesubstrat. Je mehr Laktat den Neuronen zur Verfügung steht, umso höher ist das neuronale Überleben. In dieser Arbeit konnte die Beteiligung der Laktat-Dehydrogenase an der durch das zelluläre Prion-Protein vermittelten Neuroprotektion nach Hypoxie nachgewiesen werden. Das Ziel dieser Arbeit bestand darin, mögliche Unterschiede der LDH-Expression in WT-Zellen, Prnp0/0-Zellen und HEK-293-Zellen unter normalen und hypoxischen Bedingungen in vitro zu untersuchen. Die Expression der LDH war unter hypoxischen Bedingungen in den WT-Zellen im Vergleich zu den Prnp0/0-Zellen deutlich höher. Dies konnte auch in PrPC-überexprimierenden HEK-293-Zellen nach Hypoxie gezeigt werden. Ebenso konnte nachgewiesen werden, dass Hypoxie zu einem größeren Schaden des Tubulinzytoskelettes in Prnp0/0-Zellen führt als in WT-Zellen, was eine neuroprotektive Wirkung von PrPC vermuten lässt. Eine direkte oder indirekte Interaktion von LDH-A und PrPC konnte durch eine Co-Immunpräzipitation in HEK-293-Zellen nachgewiesen werden. Die genauen Mechanismen über die PrPC möglicherweise zu einer vermehrten Laktat-Produktion führt, sind noch nicht eindeutig identifiziert und müssen noch näher untersucht werden. Zusammengefasst kann gesagt werden, dass die erhobenen Daten die Vermutung verstärken, dass das Enzym LDH und sein Produkt Laktat in die durch das zelluläre Prion-Protein vermittelte Neuroprotektion nach Hypoxie involviert sind. Es ist das erste Mal, dass gezeigt wurde, durch welchen Mechanismus PrPC zur Neuroprotektion beiträgt.

vi Title: Biochemical and mechanical processes in synovial fluid - modeling, mathematical analysis and computational simulations Author: Petra Pustějovská (petra.pustejovska@karlin.mff.cuni.cz) Department: Matematický ústav UK, Univerzita Karlova v Praze Institut für Angewandte Mathematik, Universität Heidelberg Supervisors: prof. RNDr. Josef Málek CSc., DSc. (malek@karlin.mff.cuni.cz) Matematický ústav UK, Univerzita Karlova v Praze, Prof. Dr. Dr. h.c. mult. Willi Jäger (jaeger@iwr.uni-heidelberg.de) Institut für Angewandte Mathematik, Universität Heidelberg Abstract: Synovial fluid is a polymeric liquid which generally behaves as a viscoelastic fluid due to the presence of polysaccharide molecules called hyaluronan. In this thesis, we study the biological and biochemical properties of synovial fluid, its complex rheology and interaction with synovial membrane during filtration process. From the mathematical point of view, we model the synovial fluid as a viscous incompressible fluid for which we develop a novel generalized power-law fluid model wherein the power-law exponent depends on the concentration of the hyaluronan. Such a model is adequate to describe the flows of synovial fluid as long as it is not subjected to instantaneous stimuli. Moreover, we try to find a suitable linear viscoelastic model...

This diploma thesis deals with the validation of spectral average cross-sections (SACS) of 55 Mn(n,2n)54 Mn, 90 Zr(n,2n)89 Zr, 127 I(n,2n)126 I reactions in well-defined LR-0 reactor spectrum. The measurement of SACS for selected reactions is of high interest because they are used for the practical reactor dosimetry. Various experiments for description of neutron field in reactor and detector characterization, which are necessary for validation, are described. The spectral average cross-sections are derived from Net Peak Areas of irradiated samples measured using a semiconductor high purity germanium detector. Obtained result were compared with MCNP6 calculations using ENDF/B-VII.0, ENDF/B-VII.1, JEFF-3.1, JEFF-3.2, JENDL-3.3, JENDL-4, ROSFOND-2010, CENDL-3.1 and IRDFF nuclear data libraries. Notable discrepancies were found in 90 Zr(n,2n)89 Zr and 127 I(n,2n)126 I reactions. This thesis also contains a theoretical basis for the interaction of neutrons with matter.

LIMA, Tereza Cristina Batista de. Ação educativa e tecnologias digitais: análise sobre os saberes colaborativos. 2006. 224 f. Tese (Doutorado em Educação) – Universidade Federal do Ceará, Programa de Pós-Graduação em Educação Brasileira, Fortaleza-CE, 2006. / Submitted by moises gomes (celtinha_malvado@hotmail.com) on 2012-07-17T13:49:14Z No. of bitstreams: 1 2008_tese_TCBLima.pdf: 2568880 bytes, checksum: 1cb52cf4eca59d915679f37a630bab16 (MD5) / Approved for entry into archive by Maria Josineide Góis(josineide@ufc.br) on 2012-07-17T14:29:45Z (GMT) No. of bitstreams: 1 2008_tese_TCBLima.pdf: 2568880 bytes, checksum: 1cb52cf4eca59d915679f37a630bab16 (MD5) / Made available in DSpace on 2012-07-17T14:29:45Z (GMT). No. of bitstreams: 1 2008_tese_TCBLima.pdf: 2568880 bytes, checksum: 1cb52cf4eca59d915679f37a630bab16 (MD5) Previous issue date: 2006 / The programs of distance learning that use digital technologies constitute pedagogical possibilities more and more frequent on the educational context. It is verified great expansion of experiences in distance learning that complement conventional systems, as well as the upcoming of hybrid forms of education that combine presence activities and distance activities, which promote the interchange e the integration of both systems. The digital media and the Web 2.0 tools, by collaborative platforms such as Moodle, possibilitate the communication, interactivity, collaboration and collective formulation of knowledge, transforming the traditional roles of teachers and students. Having this scenario as basis, the research tried to identify how the digital technologies and the pedagogical mediations based on co-authorship increases the collaborative knowledges - knowledge, abilities and attitudes related to collaboration - fundamental to life long learning. The theoretical approach tried to explore theories and researches about collaboration and collaborative learning; tried to define the concept of collaborative knowledge and to elect, among these, the five concepts most applicable to the collaborative dynamic in distance learning programs (EAD): autonomy, communication and sharing, exploration and resolution of conflicts, collaborative engagement and verification and synthesis. This study searched yet to retrieve central aspects of the use of digital technologies in EAD, such as digital media characteristics, hypertext, interactivity, interfaces and Web 2.0. The theoretical research highlighted the theoretic aspects that guide the concept of pedagogic mediation such as dialogue, symbolic and cultural elaboration and possibility of communication and critic. The investigation approached the relative communication models to the use of technologies in education, highlighting the EMEREC model and the concepts of authorship and co-authorship in the processes of distance teaching and learning. The field research was done in the discipline of Distance Education, of FACED-UFC, from august to December 2007, using the methodology of virtual ethnography. The data analysis is organized in three categories: collaborative knowledges, digital technologies and pedagogical mediations supported by authorship and co-authorship. The results indicate that the collaborative knowledges are lived and improved in context of use of digital technologies and pedagogical mediations based in authorship and co-authorship, which need to be improved. Indicate also that the Web 2.0 tools, although insufficiently explored, favors and induces collaborative practices and that pedagogical mediations based in authorship and co-authorship require great investment in docent formation. The research proposes the definition of public politics in management and financing, access to internet to different social segments and teacher formation towards critic and autonomy actions. / Os programas de educação a distância que utilizam tecnologias digitais constituem possibilidades pedagógicas cada vez mais recorrentes no contexto educacional. Evidencia-se grande expansão de experiências de ensino a distância que complementam os sistemas convencionais, bem como o surgimento de formas híbridas de educação que combinam atividades presenciais e a distância que promovem o intercâmbio e a integração dos dois tipos de sistemas. As mídias digitais e as ferramentas da Web 2.0, por meio de plataformas colaborativas como o Moodle, possibilitam a comunicação, interação, colaboração e formulação coletiva dos conhecimentos, transformando os tradicionais papéis de professores e alunos. Com base nesse cenário, a pesquisa procurou identificar como as tecnologias digitais e as mediações pedagógicas baseadas na co-autoria potencializam os saberes colaborativos - conhecimentos, habilidades e atitudes relacionadas à colaboração - fundamentais para a aprendizagem ao longo da vida. A abordagem teórica procurou explorar teorias e pesquisas sobre colaboração e aprendizagem colaborativa; definir o conceito de saberes colaborativos e eleger, entre estes, cinco mais fortemente aplicáveis à dinâmica colaborativa em programas de EAD: autonomia, comunicação e compartilhamento, exploração e resolução de conflitos, engajamento colaborativo e verificação e síntese. Buscou ainda reaver aspectos centrais da utilização das tecnologias digitais na EAD, como as características das mídias digitais, integração multimídia, hipertexto, interatividade, interfaces e Web 2.0. A pesquisa teórica destacou os aspectos teóricos que norteiam o conceito de mediação pedagógica como diálogo, elaboração simbólica e cultural e possibilidade de comunicação e crítica. A investigação abordou os modelos de comunicação relativos ao uso das tecnologias na educação, com destaque para o modelo EMEREC e os conceitos de autoria e co-autoria nos processos de ensino e aprendizagem. A pesquisa de campo foi realizada na disciplina Educação a Distância, da FACED- UFC, de agosto a dezembro de 2007, utilizando a metodologia da etnografia virtual. A análise de dados está organizada em três categorias: saberes colaborativos, tecnologias digitais e mediações pedagógicas esteadas na autoria e co-autoria. Os resultados indicam que os saberes colaborativos são vivenciados e aprimorados em contexto de utilização de tecnologias digitais e de mediações pedagógica baseadas na autoria e na co-autoria, que precisam ser aprimoradas. Indicam, também, que as ferramentas da web 2.0, ainda que insuficientemente exploradas, favorecem e induzem às práticas colaborativas e que as mediações pedagógicas baseadas na autoria e co-autoria requerem grande investimento na formação docente. A pesquisa sugere a definição de políticas públicas em gestão e financiamento, acesso à internet das diversas camadas sociais e formação docente voltada para ações críticas e autônomas.

La prise de décision est une partie intégrante de notre vie quotidienne où le décideur est confronté à des problèmes composés de plusieurs objectifs habituellement contradictoires. Dans ce travail, nous traitons des problèmes d'optimisation multiobjectif dans des espaces de recherche continus ou discrets. Nous avons développé plusieurs nouveaux algorithmes basés sur les métaheuristiques hybrides évolutionnaires, en particulier sur l'algorithme MOEA/D. Nous avons proposé l'algorithme HEMH qui utilise l'algorithme DM-GRASP pour construire une population initiale de solutions de bonne qualité dispersées le long de l'ensemble des solutions Pareto optimales. Les résultats expérimentaux montrent la supériorité de toutes les variantes hybrides proposées sur les algorithmes originaux MOEA/D et SPEA2. Malgré ces bons résultats, notre approche possède quelques limitations, levées dans une version améliorée de HEMH : HEMH2 et deux autres variantes HEMHde et HEMHpr. Le Adaptive Binary DE inclus dans les HEMH2 et HEMHde a de meilleures capacités d'exploration qui pallient aux capacités de recherche locale contenues dans la HEMH, HEMH2 et HEMHde. Motivés par ces résultats, nous avons proposé un nouvel algorithme baptisé HESSA pour explorer un espace continu de recherche où le processus de recherche est réalisé par différentes stratégies de recherche. Les résultats expérimentaux montrent la supériorité de HESSA à la fois sur MOEA/D et dMOPSO. Tous les algorithmes proposés ont été vérifiés, testé et comparés à certaines méthodes MOEAs. Les résultats expérimentaux montrent que toutes les propositions sont très compétitives et peuvent être considérés comme une alternative fiable / Many real-world decision making problems consist of several conflicting objectives, the solutions of which is called the Pareto-optimal set. Hybrid metaheuristics proved their efficiency in solving these problems. They tend to enhance search capabilities by incorporating different metaheuristics. Thus, we are concerned with developing new hybrid schemes by incorporating different strategies with exploiting the pros and avoiding the drawback of the original ones. First, HEMH is proposed in which the search process includes two phases DMGRASP obtains an initial set of efficient solutions in the 1st phase. Then, greedy randomized path-relinking with local search or reproduction operators explore the non-visited regions. The efficient solutions explored over the search are collected. Second, a comparative study is developed to study the hybridization of different metaheuristics with MOEA/D. The 1st proposal combines adaptive discrete differential Evolution with MOEA/D. The 2nd combines greedy path-relinking with MOEA/D. The 3rd and the 4th proposals combine both of them in MOEA/D. Third, an improved version of HEMH is presented. HEMH2 uses inverse greedy to build its initial population. Then, differential evolution and path-relink improves these solutions by investigating the non-visited regions in the search space. Also, Pareto adaptive epsilon concept controls the archiving process. Motivated by the obtained results, HESSA is proposed to solve continuous problems. It adopts a pool of search strategies, each of which has a specified success ratio. A new offspring is generated using a randomly selected one. Then, the success ratios are adapted according to the success of the generated offspring. The efficient solutions are collected to act as global guides. The proposed algorithms are verified against the state of the art MOEAs using a set of instances from literature. Results indicate that all proposals are competitive and represent viable alternatives

[pt] Algoritmos para a resolução de problemas de programação mista 0-1 gerais baseados em cortes derivados dos métodos lift-and-project, tem se mostrado bastante eficientes na prática. Estes cortes são gerados resolvendo um problema que depende de uma certa normalização. Desde um ponto de vista teórico, o bom comportamento destes algoritmos não foi completamente compreendido, especialmente no que diz respeito à normalização. Neste trabalho consideramos normalizações gerais definidas por um conjunto convexo fechado arbitrário, estendendo assim a análise teórica desenvolvida nos anos noventa. Apresentamos um marco teórico que abarca todas as normalizações previamente estudadas e introduzimos novas normalizações, analisando as propriedades dos cortes associados.Introduzimos também uma nova fórmula de atualização do parâmetro proximal para uma variante dos métodos de feixes. Estes métodos são bem conhecidos pela sua eficiência na resolução de problemas de otimização não diferenciável. Por último, propomos uma metodologia para eliminr soluções redundantes de programas inteiros combinatórios. Nossa proposta baseia-se na utilização da informação de simetria do problema, eliminam a simetria sem prejudicar a solução do problema inteiro. / [en] Algorithms for general 0-1 mixed integer programs can be successfully developed by using lift-and-project methods to generate cuts. Cuts are generated by solving a cut- generation-program that depends on a certain normalization. From a theoretical point of view, the good numerical behavior of these cuts is not completely understood yet, specially, concerning to the normalization chosen. We consider a general normalization given by an arbitrary closed convex set, extending the theory developed in the 90's. We present a theoretical framework covering a wide group of already known normalizations. We also introduce new normalizations and analyze the properties of the associated cuts. In this work, we also propose a new updating rule for the prox parameter of a variant of the proximal bundle methods, making use of all the information available at each iteration. Proximal bundle methods are well known for their efficiency in nondifferentiable optimization. Finally, we introduce a way to eliminate redundant solutions ( due to geometrical symmetries ) of combinatorial integer program. This can be done by using the information about the problem symmetry in order to generate inequalities, which added to the formulation of the problem, eliminate this symmetry without affecting solution of the integer problem. / [es] Los algoritmos para la resolución de problemas de programación mixta 0-1 generales que utilizan cortes derivados de los métodos lift-and-project, se han mostrado bastante eficientes en la práctica. Estos cortes se generan resolviendo un problema que depende de una cierta normalización. Desde el punto de vista teórico, el buen comportamiento de estos algoritmos no fue completamente comprendido, especialmente respecto a la normalización. En este trabajo consideramos normalizaciones generales definidas por un conjunto convexo cerrado arbitrario, extendiendo así el análisis teórico desarrollado en los años noventa. Presentamos un marco teórico que abarca todas las normalizaciones previamente estudiadas e introducimos nuevas normalizaciones, analizando las propiedades de los cortes asociados. Introducimos una nueva fórmula de actualización del parámetro de. Estoss métodos son bien conocidos por su eficiencia en la resolución de problemas de optimización no diferenciable. Por último, proponemos una metodología para eliminar soluciones redundantes de programas enteros combinatorios. Nuestra propuesta se basa en la utilización de la información de simetría del problema, eliminan la simetría sin perjudicar la solución del problema entero.

Presents results of research in the field of low-level electromagnetic fields interacting with the higher organisms, in the frequency band from 0,01 to 30 Hz effect on the individual or social group. Provides a description of the methodology of measuring and evaluating the impact of workplace assembled measuring low-level electromagnetic fields, extremely low frequency (ELF) on a sample of respondents. It was proposed measuring device for monitoring and evaluating how respondents' reactions to changes in the geomagnetic or external - external magnetic / electromagnetic field and to work for the measurement and evaluation of changes in external magnetic fields very low levels (ELF). This work is designed to process and evaluate implemented within experimental research into the influence of low-level magnetic fields in the Earth's resonator psychophysiological parameters of human organism and its behavior and decision-making. The work confirmed the influence of low-level magnetic fields on the psychophysiological parameters of the organism to be simultaneously confirmed the hypothesis established in accordance with the objectives of work.

Cette thèse comporte des résultats théoriques et pratiques sur deux métaheuristiques, la Recherche Dispersée et la Recherche Voisinage variable (RVV), ainsi que sur des Matheuristiques. Au niveau théorique, la contribution principale de cette thèse est la proposition d’un algorithme de recherche dispersée avec l’arrondi directionnel convergent pour les programmes en nombres entiers mixtes (0-1 MIP), avec une preuve de cette convergence en un nombre fini d’itérations. En se basant sur cet algorithme convergeant, deux implémentations et plusieurs heuristiques sont proposées et testées sur des instances de 0-1 MIP. Les versions testées reposent sur des implémentations non optimisées pour mettre en évidence la puissance des approches dans une forme simplifiée. Nos résultats démontrent l’efficacité de ces approches initiales, ce qui les rend attractives lorsque des solutions de très haute qualité sont recherchées avec un investissement approprié en termes d’effort de calcul. Cette thèse inclut également quelques nouvelles variantes de la métaheuristique Recherche Voisinage Variable telles qu’une recherche voisinage variable deux niveaux, une recherche voisinage variable imbriquée, une descente voisinage variable cyclique et une heuristique de plongée voisinage variable. En outre, plusieurs implémentations efficaces de ces algorithmes basés sur la recherche voisinage variable ont été appliquées avec succès à des problèmes NP-Difficiles apparaissant en transport, logistique, production d’énergie, ordonnancement, et segmentation. Les heuristiques proposées se sont avérées être les nouvelles heuristiques de référence sur tous les problèmes considérés. La dernière contribution de cette thèse repose sur la proposition de plusieurs matheuristiques pour résoudre le problème de Conception de Réseau Multi-flots avec Coût fixe (CRMC). Les performances de ces matheuristiques ont été évaluées sur un ensemble d’instances de référence du CRMC. Les résultats obtenus démontrent la compétitivité des approches proposées par rapport aux approches existantes de la littérature. / This thesis consists of results obtained studying Scatter Search, Variable Neighbourhood Search (VNS), and Matheuristics in both theoretical and practical context. Regarding theoretical results, one of the main contribution of this thesis is a convergent scatter search with directional rounding algorithm for 0-1 Mixed Integer Programs (MIP) with the proof of its finite convergence. Besides this, a convergent scatter search algorithm is accompanied by two variants of its implementation. Additionally, several scatter search based heuristics, stemming from a convergent scatter search algorithm have been proposed and tested on some instances of 0-1 MIP. The versions of the methods tested are first stage implementations to establish the power of the methods in a simplified form. Our findings demonstrate the efficacy of these first stage methods, which makes them attractive for use in situations where very high quality solutions are sought with an efficient investment of computational effort.This thesis also includes new variants of Variable Neighborhood Search metaheuristic such as a two-level variable neighborhood search, a nested variable neighborhood search, a cyclic variable neighborhood descent and a variable neighborhood diving. Additionally, several efficient implementation of those variable neighborhood search algorithms have been successfully applied for solving NP-Hard problems appearing in transportation, logistics, power generation, scheduling and clustering. On all tested problems, the proposed VNS heuristics turned out to be a new state-of-the art heuristics. The last contribution of this thesis consists of proposing several matheuristics for solving Fixed-Charge Multicommodity Network Design (MCND) problem. The performances of these matheuristics have been disclosed on benchmark instances for MCND. The obtained results demonstrate the competitiveness of the proposed matheuristics with other existing approaches in the literature.

La classe des graphes quasi-médians est une généralisation des graphes médians, ou de manière équivalente, des complexes cubiques CAT(0). L'objectif de cette thèse est d'introduire ces graphes dans le monde de la théorie géométrique des groupes. Dans un premier temps, nous étendons la notion d'hyperplan définie dans les complexes cubiques CAT(0), et nous montrons que la géométrie d'un graphe quasi-médian se réduit essentiellement à la combinatoire de ses hyperplans. Dans la deuxième partie de notre texte, qui est le cœur de la thèse, nous exploitons la structure particulière des hyperplans pour démontrer des résultats de combinaison. L'idée principale est que si un groupe agit d'une bonne manière sur un graphe quasi-médian de sorte que les stabilisateurs de cliques satisfont une certaine propriété P de courbure négative ou nulle, alors le groupe tout entier doit satisfaire P également. Les propriétés que nous considérons incluent : l'hyperbolicité (éventuellement relative), les compressions lp (équivariantes), la géométrie CAT(0) et la géométrie cubique. Finalement, la troisième et dernière partie de la thèse est consacrée à l'application des critères généraux démontrés précédemment à certaines classes de groupes particulières, incluant les produits graphés, les groupes de diagrammes introduits par Guba et Sapir, certains produits en couronne, et certains graphes de groupes. Les produits graphés constituent notre application la plus naturelle, où le lien entre le groupe et son graphe quasi-médian associé est particulièrement fort et explicite; en particulier, nous sommes capables de déterminer précisément quand un produit graphé est relativement hyperbolique. / The class of quasi-median graphs is a generalisation of median graphs, or equivalently of CAT(0) cube complexes. The purpose of this thesis is to introduce these graphs in geometric group theory. In the first part of our work, we extend the definition of hyperplanes from CAT(0) cube complexes, and we show that the geometry of a quasi-median graph essentially reduces to the combinatorics of its hyperplanes. In the second part, we exploit the specific structure of the hyperplanes to state combination results. The main idea is that if a group acts in a suitable way on a quasi-median graph so that clique-stabilisers satisfy some non-positively curved property P, then the whole group must satisfy P as well. The properties we are interested in are mainly (relative) hyperbolicity, (equivariant) lp-compressions, CAT(0)-ness and cubicality. In the third part, we apply our general criteria to several classes of groups, including graph products, Guba and Sapir's diagram products, some wreath products, and some graphs of groups. Graph products are our most natural examples, where the link between the group and its quasi-median graph is particularly strong and explicit; in particular, we are able to determine precisely when a graph product is relatively hyperbolic.