Les protéines amyloïdes sont retrouvées sous forme de fibres dans de nombreuses maladies neurodégénératives. En tentant d’élucider le mécanisme de fibrillation, les chercheurs ont découvert que cette réaction se fait par un phénomène de nucléation passant par des oligomères. Il semblerait que ces espèces soient la principale cause de la toxicité observée dans les cellules des patients atteints d’amyloïdose. C’est pourquoi un intérêt particulier est donc porté aux premières étapes d’oligomérisation. Dans ce mémoire, nous nous intéressons à une séquence d’acide aminé fortement hydrophobe de l’α-synucléine appelée composante non β -amyloïde (Non-Amyloid β Component ou NAC). Cette dernière est retrouvée sous forme de fibres dans les corps et les neurites de Lewy des patients atteints de la maladie de Parkinson. De plus, elle constitue une composante minoritaire des fibres impliquées dans la maladie d’Alzheimer. Nous avons observé les changements structuraux qui ont lieu pour le monomère, le dimère et le trimère de la séquence NAC de l’α-synucléine. Nous nous sommes aussi intéressés aux conséquences structurelles observées dans des oligomères hétérogènes qui impliqueraient, Aβ1−40. Pour cela nous utilisons des dynamiques moléculaires, d’échange de répliques couplées au potentiel gros-grain, OPEP. Nous constatons une disparition des hélices α au profit des feuillets β , ainsi que le polymorphisme caractéristique des fibres amyloïdes. Certaines régions se sont démarquées par leurs capacités à former des feuillets β . La disparition de ces régions lorsque NAC est combinée à Aβ laisse entrevoir l’importance de l’emplacement des résidus hydrophobes dans des structures susceptibles de former des fibres amyloïdes. / Amyloid proteins are found in fiber form in many neurodegenerative diseases. In attempting to elucidate the mechanism of fibrillation, researchers have found that fibril formation occurs by a nucleation mechanisms involving oligomers. It seems, in particular, that the latter species are responsible for the toxicity observed in the cells of patients suffering from amyloidosis. That is why special interest is focused in the early stages of oligomerization. In this this work, we focus on a highly hydrophobic amino acid sequence of the α-synuclein called Non-Amyloid β Component (NAC). The NAC is recovered in the form of fibers in the body and Lewy neurites in patients with Parkin- son’s disease. Moreover, it is a minority component of the fibers involved in Alzheimer’s disease. In particular, we observe the structural changes taking place for the monomer, dimer and trimer of the NAC region of α-synuclein. We are also interested in the structural consequences observed in heterogeneous oligomers which involve Aβ1−40. We use Hamiltonian and temperature replica exchange molecular dynamics (HT-REMD) simulations combined with the coarse-grained OPEP potential. We observe a loss of α-helices in favor of β -strands and the characteristic polymorphism of amyloid fibers. We also find that some regions are distinguished by their ability to form β -strands. The disappearance of these regions when combined Aβ with NAC suggests the importance of the location of hydrophobic residues in amyloid fibers structures.

Les propriétés mécaniques des polymères et des copolymères à blocs ont été étudiées par simulation de type dynamique moléculaire (modèle billes-ressorts). Les échantillons polymères ont été générés par la méthode de « radical like polymerisation ». Ces échantillons ont été soumis à des essais de traction uniaxiaux et triaxiaux dans le but d’étudier leurs réponses mécaniques. Dans la première partie de ce travail on a comparé deux méthodes de traction : « méthode de traction homogène» et la traction « pilotée par les bords » de l’échantillon. Les résultats montrent que les deux méthodes sont équivalentes à faible vitesse de traction. Le changement de distance entre enchevêtrement dans un polymère modèle sous traction est analysé, les résultats montrent que le désenchevêtrèrent des chaines est plus prononcé lorsque la déformation de l’échantillon est uniaxiale du fait de la relaxation latérale de l’échantillon. La nucléation des cavités dans les polymères amorphes soumis à une déformation triaxial a été également étudiée. On a trouvé que les cavités se forment dans des zones qui sont caractérisées par un faible module d’incompressibilité élastique. Ces zones sont identifiables dès le début de la déformation à une température très basse (T~0K). La seconde partie de ce travail se concentre sur la simulation de la réponse mécanique des copolymères à blocs. L’influence de l’architecture moléculaire sur le comportement mécanique de l’échantillon a été analysée. Les résultats montrent que le comportement mécanique des échantillons est piloté par le taux des chaines liantes qui assurent la transmission des contraintes entre les phases. Le flambement des lamelles dans les copolymères à blocs a été également étudié, l’influence de la taille de l’échantillon et de la vitesse de déformation sur la réponse mécanique de l’échantillon a été explorée. Les résultats montrent un changement de mode du flambement selon la vitesse de déformation imposée. Un nouveau modèle qui prend en compte le facteur cinétique du flambement est proposé pour décrire la compétition entre les modes. / We use molecular dynamics simulation of a coarse grained model to investigate the mechanical properties of homogenous polymers and lamellar block copolymers. Polymer samples have been generated using “radical like polymerisation” method. These samples were submitted to uniaxial and triaxial tensile tests in order to study their mechanical responses. First we compare two tensile test methods: the “homogenous deformation method” and the “boundary driven deformation method”. We find that the two methods lead to similar results at low strain rate. The change of the entanglement network in polymer sample undergoing a tensile deformation was investigated. We have found that the sample exhibits an increase of its entanglement length in uniaxial deformation test compared to triaxial deformation one. Our finding was interpreted by the pronounced chain disentanglement observed in the uniaxial deformation test due to the lateral relaxation of the sample. The cavity nucleation in amorphous polymers has been also studied. We have found that the cavities nucleate preferentially in zones that exhibit a low elastic bulk modulus. These zones can be identified from the initial undeformed state of the sample at low temperature (T~0K). The second part of the work focused in the simulation of the mechanical response of block copolymers. The influence of chain architecture on the mechanical properties was investigated: our finding reveals an important role of the bridging molecules (cilia chains and knotted loop chains) on the stress transmission between phases at high strain. The initiation of plasticity in copolymer samples was also studied. The role of the buckling has been found to be determinant in the mechanical response of the sample The dependence of the buckling instability with the sample size and the deformation rate was investigated. We have found that the fundamental (first) mode of buckling develops at relatively low strain rate whereas at high strain rate the buckling of the sample occurs with the second or higher mode of buckling. A new model that takes into account the buckling kinetic was developed to describe this competition between the buckling modes.

Nous proposons un algorithme basé sur une approche orientée d'ensemble de système dynamique pour extraire une organisation grossière de l'espace d'état de cerveau sur la base des signaux de l'EEG. Nous l'utilisons pour comparer l'organisation de l'espace d'état des données simulées à grande échelle avec la dynamique cérébrale réelle au repos chez des sujets sains et pathologiques (SEP). / We propose an algorithme based on set oriented approach of dynamical system to extract a coarse grained organization of brain state space on the basis of EEG signals. We use it for comparing the organization of the state space of large scale simulation of brain dynamics with actual brain dynamics of resting activity in healthy and SEP subjects.

A micromanufatura via usinagem apresenta algumas dificuldades, principalmente aquelas relacionadas à formação do cavaco, pois a espessura de corte passa a ter a dimensão do tamanho de grão do material da peça e da microgeometria da aresta de corte. Em operações de microcorte, a microestrutura do material é um fator importante no controle da geração da superfície da peça, mecanismo de formação de cavaco, etc. Este trabalho de pesquisa avaliou o efeito do tamanho ultrafino dos grãos do material da peça sobre os fenômenos inerentes ao corte no microfresamento. As variáveis de usinagem investigadas foram avanço por dente (fz), velocidade de corte (vc), diâmetro da microfresa (d&#934) e raio de aresta de corte (re), visando avaliar o mecanismo de formação do cavaco, acabamento da peça e integridade superficial. Os materiais utilizados nos experimentos foram um aço bifásico (ferrita-perlita) com tamanho de grão ferrítico de 11 µm e outro de microestrutura homogênea de grãos ultrafinos com 0,7 µm, ambos com mesma composição química e baixo-carbono. Dois grupos de ensaios foram propostos: (1) macro e microfresamento e (2) microfresamento de canais. O tipo de usinagem foi o de fresamento de topo, sem emprego de fluido de corte. Os ensaios de usinagem foram executados em centros de usinagem CNC. As ferramentas de corte foram de metal duro com recobrimentos, diâmetro 16 mm na escala macro de usinagem, 200 e 800 µm na escala micro. A adequação da microestrutura do material da peça à redução da escala de usinagem, através do mecanismo de refino de grão, gerou alguns aspectos favoráveis à microusinagem, como melhor acabamento (Ssk≈0 e Sku≈3), formação de cavaco contínuo e menor formação de rebarbas com a redução da espessura de corte (fz&#8804re), possibilitando aplicações em microfabricação por corte com ferramenta de geometria definida utilizando aços baixo carbono, antes limitadas à estruturas na construção civil e peças obtidas por conformação mecânica. / Micro manufacturing by means of machining presents difficulties, mainly those related to chip formation, since chip thickness become as small as normal material grain size, as well as the cutting edge radius. At such micro cutting operations material microstructure ascends as a very important issue in terms of machining output, i.e. surface roughness, subsurface damages, cutting forces, etc. This research evaluated the effect of the intervention on the metallurgical microstructure of the material on the cutting phenomena inherent in micromachining. The variables investigated were the feed per tooth (ft), cutting speed (vc), micro end-mill diameter (d&#934) and cutting edge radius (re). The materials used in the experiments were a steel two-phase (ferrite-pearlite) with ferritic grain size of 11 µm and similar one with homogeneous microstructure and ultrafine grains (0.7 µm), both low carbon. The mechanism of chip formation, surface finish and surface integrity were investigated and correlated with the studied variables. Two groups of machining experiments were proposed: (1) macro and micro end-milling and (2) microchannels. Overall, the type of machining was the end milling, without using cutting fluid. The machining tests were carried on a CNC machining center. The cutting tools are coated, diameter 16 mm in macro scale of machining, 200 and 800 &#956m in micro scale. the adequacy of the microstructure of the workpiece material to the reduce the scale of machining generated some favorable aspects to micromachining, such as better finishing (Ssk≈0 e Sku≈3), continuous chip formation and lesser burr formation by reducing the cutting thickness (fz&#8804re), enabling micromanufacturing applications for low carbon steels, once limited to structures in the civil construction and pieces obtained by mechanical forming.

Um grande número de rochas de granulação grosseira tem valor agregado muito alto quando usadas como materiais de construção, as chamadas rochas exóticas. No entanto, existem problemas com a utilização desses materiais dado a sua fragilidade, que está relacionada com a sua textura muito heterogênea. No Brasil é empregado empiricamente um reforço (compósito) que utiliza resina epóxi e fibra de vidro para melhorar o desempenho mecânico de tais rochas quando empregadas como materiais de construção. Os objetivos da presente pesquisa foram estudar o reforço tradicional brasileiro (telagem) para determinar sua eficiência e, ao mesmo tempo, propor outras soluções de reforço alternativas e mais eficientes, e avaliá-las através da caracterização mecânica experimental. Foi proposto um critério denominado Declive Global para avaliar as tensões de serviço dos materiais pegmatíticos estudados, quando os reforços propostos foram aplicados. Para validar esse critério foi utilizado um sistema de correlação digital de imagem (CDI) para observar e medir o comportamento de deformação e fratura durante a realização de testes de flexão em 4 pontos. Tanto o critério proposto como a CDI mostraram que a propagação de fissuras ocorre muito antes do material atingir a carga máxima. O reforço alternativo proposto, que emprega resina epóxi e uma fibra de vidro 600 g/m² apresentou o melhor desempenho mecânico, elevando a carga de ruptura até 6x em comparação com as amostras onde nenhum reforço foi aplicado. Os resultados demonstrados pelos reforços propostos são promissores e aumentam a possibilidade de aplicar rochas exóticas frágeis como materiais de construção, além do critério proposto fornecer uma ferramenta importante para a compreensão mecânica prévia de produtos de rocha que utilizam reforços compósitos. / A great number of coarse-grained natural stones have very high added-value when used as building materials, the so called exotic stones. However, problems using these materials arise from its brittleness behavior, which are related to its very heterogeneous texture. Glass fiber-reinforced epoxy composite (GFRC) is being used to improve mechanical performance of such stones when employed as building materials. The objectives of this present investigation it were studying the Brazilian traditional reinforcement to determinate its efficiency and, at the same time, a number of alternative solutions were proposed and evaluated through experimental mechanical characterization. It was proposed a slope-based criterion to evaluate the useful service loads of pegmatitic materials when glass fiber-reinforcement is applied. To validate the proposed criterion, a digital image correlation (DIC) system was employed to observe and measure strain and fracture behavior during the realization of 4-point bending tests. Both proposed criterion and DIC show that crack propagation occurs long before the material reaches maximum load. GFRC acts as a crack inhibitor, raising the breaking load up to 6x in comparison with the specimens where no reinforcement was applied. The results from this study enhance the capability to apply such materials as building materials and provide an important tool to perform prior mechanical understanding of stone products using GFRC.

"Because many software systems used for business today are considered legacy systems, the need for software evolution techniques has never been greater. We propose a novel evolution methodology for legacy systems that integrates the concepts of features, regression testing, and Component-Based Software Engineering (CBSE). Regression test suites are untapped resources that contain important information about the features of a software system. By exercising each feature with its associated test cases using code profilers and similar tools, code can be located and refactored to create components. The unique combination of Feature Engineering and CBSE makes it possible for a legacy system to be modernized quickly and affordably. We develop a new framework to evolve legacy software that maps the features to software components refactored from their feature implementation. In this dissertation, we make the following contributions: First, a new methodology to evolve legacy code is developed that improves the maintainability of evolved legacy systems. Second, the technique describes a clear understanding between features and functionality, and relationships among features using our feature model. Third, the methodology provides guidelines to construct feature-based reusable components using our fine-grained component model. Fourth, we bridge the complexity gap by identifying feature-based test cases and developing feature-based reusable components. We show how to reuse existing tools to aid the evolution of legacy systems rather than re-writing special purpose tools for program slicing and requirement management. We have validated our approach on the evolution of a real-world legacy system. By applying this methodology, American Financial Systems, Inc. (AFS), has successfully restructured its enterprise legacy system and reduced the costs of future maintenance. "

The principal objective of this work was to elucidate the effect of microstructural features on the intrinsic dislocation mechanisms in two FCC alloys. First alloy Al0.1CoCrFeNi was from a new class of material known as complex concentrated alloys, particularly high entropy alloys (HEA). The second was a conventional Al-Mg-Sc alloy in ultrafine-grained (UFG) condition. In the case of HEA, the lattice possess significant lattice strain due to the atomic size variation and cohesive energy differences. Moreover, both the lattice friction stress and the Peierls barrier height are significantly larger than the conventional FCC metals and alloys. The experimental evidences, so far, provide a distinctive identity to the nature and motion of dislocations in FCC HEA as compared to the conventional FCC metals and alloys. Hence, the thermally activated dislocation mechanisms and kinetics in HEA has been studied in detail. To achieve the aim of examining the dislocation kinetics, transient tests, both strain rate jump tests and stress relaxation tests, were conducted. Anomalous behavior in dislocation kinetics was observed. Surprisingly, a large rate sensitivity of the flow stress and low activation volume of dislocations were observed, which are unparalleled as compared to conventional CG FCC metals and alloys. The observed trend has been explained in terms of the lattice distortion and dislocation energy framework. As opposed to the constant dislocation line energy and Peierls potential energy (amplitude, ΔE) in conventional metals and alloys, both line energy and Peierls potential undergo continuous variation in the case of HEA. These energy fluctuations have greatly affected the dislocation mobility and can be distinctly noted from the activation volume of dislocations. The proposed hypothesis was tested by varying the grain size and also the test temperature. Activation volume of dislocations was a strong function of temperature and increased with temperature. And the reduction in grain size did not affect the dislocation mechanisms and kinetics. This further bolstered the hypothesis. The second part deals with deformation characteristics of Al-Mg-Sc alloy. The microstructure obtained from the severe plastic deformation (SPD) techniques differ in dislocation density, grain/cell size, and in the grain boundary character distribution. Therefore, it is vital to understand the deformation behavior of the UFG materials produced by various SPD techniques, as the microstructural features basically control the deformation mechanisms. In this study, a detailed analysis was made to understand the deformation mechanisms operative in various regimes of a stress-strain in UFG Al-Mg-Sc alloy produced via friction stir processing. The stress-strain curves exhibited serrations from the onset of yielding to the point of sample failure. The serration amplitude and frequency was higher in UFG material as compared to CG material. Furthermore, the microstructural features that result in the serrated flow were investigated along with the avalanche characteristics. The presence of both ultrafine grains and Al3Sc precipitates were the necessary conditions to reach the critical stress required to push the grain boundary into a critical state to set off an avalanche. The microstructural conditions that did not satisfy both the requirements did not exhibit deep serrations.

A micromanufatura via usinagem apresenta algumas dificuldades, principalmente aquelas relacionadas à formação do cavaco, pois a espessura de corte passa a ter a dimensão do tamanho de grão do material da peça e da microgeometria da aresta de corte. Em operações de microcorte, a microestrutura do material é um fator importante no controle da geração da superfície da peça, mecanismo de formação de cavaco, etc. Este trabalho de pesquisa avaliou o efeito do tamanho ultrafino dos grãos do material da peça sobre os fenômenos inerentes ao corte no microfresamento. As variáveis de usinagem investigadas foram avanço por dente (fz), velocidade de corte (vc), diâmetro da microfresa (d&#934) e raio de aresta de corte (re), visando avaliar o mecanismo de formação do cavaco, acabamento da peça e integridade superficial. Os materiais utilizados nos experimentos foram um aço bifásico (ferrita-perlita) com tamanho de grão ferrítico de 11 µm e outro de microestrutura homogênea de grãos ultrafinos com 0,7 µm, ambos com mesma composição química e baixo-carbono. Dois grupos de ensaios foram propostos: (1) macro e microfresamento e (2) microfresamento de canais. O tipo de usinagem foi o de fresamento de topo, sem emprego de fluido de corte. Os ensaios de usinagem foram executados em centros de usinagem CNC. As ferramentas de corte foram de metal duro com recobrimentos, diâmetro 16 mm na escala macro de usinagem, 200 e 800 µm na escala micro. A adequação da microestrutura do material da peça à redução da escala de usinagem, através do mecanismo de refino de grão, gerou alguns aspectos favoráveis à microusinagem, como melhor acabamento (Ssk≈0 e Sku≈3), formação de cavaco contínuo e menor formação de rebarbas com a redução da espessura de corte (fz&#8804re), possibilitando aplicações em microfabricação por corte com ferramenta de geometria definida utilizando aços baixo carbono, antes limitadas à estruturas na construção civil e peças obtidas por conformação mecânica. / Micro manufacturing by means of machining presents difficulties, mainly those related to chip formation, since chip thickness become as small as normal material grain size, as well as the cutting edge radius. At such micro cutting operations material microstructure ascends as a very important issue in terms of machining output, i.e. surface roughness, subsurface damages, cutting forces, etc. This research evaluated the effect of the intervention on the metallurgical microstructure of the material on the cutting phenomena inherent in micromachining. The variables investigated were the feed per tooth (ft), cutting speed (vc), micro end-mill diameter (d&#934) and cutting edge radius (re). The materials used in the experiments were a steel two-phase (ferrite-pearlite) with ferritic grain size of 11 µm and similar one with homogeneous microstructure and ultrafine grains (0.7 µm), both low carbon. The mechanism of chip formation, surface finish and surface integrity were investigated and correlated with the studied variables. Two groups of machining experiments were proposed: (1) macro and micro end-milling and (2) microchannels. Overall, the type of machining was the end milling, without using cutting fluid. The machining tests were carried on a CNC machining center. The cutting tools are coated, diameter 16 mm in macro scale of machining, 200 and 800 &#956m in micro scale. the adequacy of the microstructure of the workpiece material to the reduce the scale of machining generated some favorable aspects to micromachining, such as better finishing (Ssk≈0 e Sku≈3), continuous chip formation and lesser burr formation by reducing the cutting thickness (fz&#8804re), enabling micromanufacturing applications for low carbon steels, once limited to structures in the civil construction and pieces obtained by mechanical forming.

The strain rate dependent behaviour of fine grained soils is an important aspect of geotechnical engineering. During dynamic or rapid events such as earthquakes and rapid pile testing, a fine grained soil will display significantly different behaviour than may be observed over the long life span of a structure. There is currently little understanding of the factors which influence the behaviour of fine grained soils during dynamic events (extremely high strain rates), making their response difficult to predict. This research investigates the behaviour of fine grained soils subjected to a wide range of constant strain rates in monotonic triaxial compression testing. Each test is conducted under drained conditions to observe the behaviour of soils as they transition from a drained response at lower strain rates, through to an undrained or viscous response at higher strain rate tests. Where the response of soils is drained or partially drained, higher strain rate tests measure a decrease in strength. The point of transition from partially drained to undrained behaviour corresponds to the lowest strain rate dependent strength. Further tests at higher strain rates measure consistently greater strength. The strain rate dependence of three fine grained soils is investigated, enabling a comparison of strain rate effects with soil index properties. The influence of initial state on the strain rate dependence of these Kaolin based model soils is also evaluated. The drained to partially drained response of the soils to strain rate increase is controlled by the coefficient of consolidation. Tests at high strain rates show the undrained or viscous strain rate effect on strength is related to liquidity index. Local strain instrumentation allowed comparison of strain rate effects on small strain stiffness. At higher strain rate the soils display increasingly linear behaviour. At non-linear elastic strains, liquidity index appears to control the magnitude of the strain rate effects on stiffness.

<p>Computation-intensive algorithms require a high level of parallelism and programmability, which </p><p>make them good candidate for hardware acceleration using fine-grained processor arrays. Using </p><p>Hardware Description Language (HDL), it is very difficult to design and manage fine-grained </p><p>processing units and therefore High-Level Language (HLL) is a preferred alternative. </p><p> </p><p>This thesis analyzes HLL programming of fine-grained architecture in terms of achieved </p><p>performance and resource consumption. In a case study, highly computation-intensive algorithms </p><p>(interpolation kernels) are implemented on fine-grained architecture (FPGA) using a high-level </p><p>language (Mitrion-C). Mitrion Virtual Processor (MVP) is extracted as an application-specific </p><p>fine-grain processor array, and the Mitrion development environment translates high-level design </p><p>to hardware description (HDL). </p><p> </p><p>Performance requirements, parallelism possibilities/limitations and resource requirement for </p><p>parallelism vary from algorithm to algorithm as well as by hardware platform. By considering </p><p>parallelism at different levels, we can adjust the parallelism according to available hardware </p><p>resources and can achieve better adjustment of different tradeoffs like gates-performance and </p><p>memory-performance tradeoffs. This thesis proposes different design approaches to adjust </p><p>parallelism at different design levels. For interpolation kernels, different parallelism levels and </p><p>design variants are proposed, which can be mixed to get a well-tuned application and resource </p><p>specific design.</p>