Assessing tall building oscillation is a multidisciplinary area involving knowledge from different fields of study: structural engineering, wind engineering, reliability, and even human physiology, to name a few. With the modern high strength structural materials and the latest tendencies in tall buildings construction, new structural systems have become slender and new buildings have reached greater heights as time passes. This context leads to a situation where these slender structures are sensitive to dynamic effects from wind loads and where human comfort is often the prevailing criterion for the structural design. This multidisciplinary area with slender structural systems allied to economic and environmental aspects from building construction demands a better integration between the abovementioned fields in order to achieve both human comfort and sustainable buildings (from environmental and economic points of view). This thesis aims at connecting the \"weak links\" of the Davenport\'s chain of wind loading, discussing criteria from each field involved in the oscillation assessment of a tall building: dynamic analysis, finite element modelling, wind climate modelling and comfort assessment. The axis of investigation intends to bring precision to the procedure, whilst creating a reliable set of criteria to perform a dynamic response assessment from the wind tunnel testing of tall buildings. This thesis also aims at connecting these fields of study by bringing understanding from each one of them to all the others, and at validating multidisciplinary interactions in the Davenport\'s chain. Finally, a wide dispersion of results is obtained for two different tall buildings in São Paulo. This dispersion serves to corroborate the deficient integration between these fields of study and to present a set of criteria that brings precision to the procedure, whilst allowing more economic and sustainable designs. / O estudo das oscilações de edifícios altos sob ação do vento é uma área multidisciplinar que envolve conhecimentos de diferentes campos de estudo: engenharia estrutural, engenharia de vento, confiabilidade e até fisiologia humana, para citar apenas alguns. Em paralelo, a criação de novos materiais de construção de alta resistência, aliados às últimas tendências na construção de edifícios altos, permite sistemas estruturais cada vez mais esbeltos aplicados a edifícios cada vez mais altos. Este contexto leva a uma situação em que estes sistemas estruturais são sensíveis aos efeitos dinâmicos das cargas de vento e onde o conforto humano é frequentemente o critério preponderante para o projeto estrutural. Esta área multidisciplinar, com seus sistemas estruturais esbeltos, aliada aos aspectos econômicos e ambientais da construção de edifícios altos, exige uma melhor integração entre os campos acima referidos para se alcançar conforto humano em edifícios sustentáveis (tanto do ponto de vista ambiental quanto do econômico). Esta tese tem como eixo de investigação os \"elos fracos\" da corrente de cargas de vento de Davenport e discute os critérios de cada campo envolvido na avaliação das oscilações de um edifício alto: análise dinâmica, modelagem de elementos finitos, modelagem probabilística de vento e avaliação de conforto. O eixo de investigação proposto visa a trazer precisão ao procedimento, criando um conjunto de critérios confiáveis para a avaliação da resposta dinâmica a partir de ensaios em túnel de vento de edifícios altos. Esta tese também visa a conectar estes campos de estudo, trazendo a compreensão de cada um deles para todos os outros e para validar as interações multidisciplinares na corrente de Davenport. Finalmente, uma grande dispersão de resultados é obtida para dois edifícios altos em São Paulo. Esta dispersão serve para corroborar a deficiência da integração entre estes campos de estudo e para apresentar um conjunto de critérios que traga precisão ao procedimento, permitindo, concomitantemente, projetos mais econômicos e sustentáveis.

Essa tese tem o objetivo modelar um subconjunto de peças de um compressor hermético de refrigeração idealizado utilizando um programa de elementos finitos para estudar a pressão de contato na junta da placa de válvulas com e sem pressão de gás refrigerante. Nessa pesquisa também se faz a modelagem dinâmica da bomba de um compressor acadêmico com vistas a estudar a vibração gerada durante seu funcionamento. No estudo da junta de vedação se faz um modelo geométrico do conjunto cabeçote e juntas com um programa CAD. A partir da geometria do subconjunto um modelo físico é construído no ANSYS®, que leva em consideração as diferentes propriedades dos materiais do conjunto cabeçote e juntas, inclusive a não linearidade do material da junta. São feitas simulações aplicando diferentes valores de força normal nos parafusos do cabeçote. No estudo de vibração do compressor faz-se o modelo de CAD da bomba de onde se obtém seu peso e propriedades de inércia. A matriz de rigidez do sistema de suspensão da bomba é calculada e se faz a análise modal da bomba. Os resultados das análises de pressão de contato foram mostrados através de gráficos da normal closure e da normal pressure da junta. Eles indicam de forma clara as regiões de baixa pressão de contato aplicada pelas peças que estão ou deveriam estar comprimindo a junta de vedação, que seriam regiões de falhas. Na análise dinâmica da bomba do compressor, é calculada a matriz de rigidez total do sistema com as molas de suspensão, levando em consideração a rigidez compressiva, de flexão e cisalhante das molas. Com a solução do modelo dinâmico criado, calcula-se a matriz dinâmica, a matriz modal normalizada, a matriz de frequências características, o deslocamento <span style=\"font-style:italic\">X <span style=\"position: relative; bottom: 1.3ex; letter-spacing: -1.2ex; right: 1.2ex\">&#8594; da bomba e também as energias cinética e potencial da bomba devido às forças de agitação. O modelo de elementos finitos da junta da placa de válvulas tem resultados coerentes e o modelo dinâmico da bomba fornece vários resultados para a análise de vibração de compressores. / This thesis has as objective to model a subset of parts of an idealized hermetic compressor for refrigeration using a program of finite elements intended to study the contact pressure on the valve plate gasket with and without pressure from the refrigerant gas. In this research a dynamic modelling of an academic compressor pump is also made with the aim of studying the vibration generated during its functioning. In the study of the sealing gasket, a geometric model of the cylinder head and gasket assembly is made by using a CAD program. From the geometric of the subset a physical model is built on the ANSYS®, which takes into account the different properties of the cylinder head and gasket assembly materials, including the non-linearity of the gasket material. Simulations are made by applying different normal force values on the cylinder head screws. In the compressor vibration study, a CAD pump model is made, thus obtaining its weight and inertia properties. The stiffness matrix of the pump suspension system is calculated and a modal analysis of the pump is made. The results from the contact pressure analyses were shown through \"normal closure\" and \"normal pressure\" charts of the gasket. They show in clear form the low contact pressure regions applied by the parts that are or should be compressing the sealing gasket, which would the regions of failures. In the dynamic analysis of the compressor pump, the total stiffness matrix of the system is calculated with the suspension springs, taking into account the compressive, flexural and shearing rigidities of the springs. With the solution of the dynamic model created, the following are calculated: the dynamic matrix, the normalized modal matrix, the characteristics frequency matrix, the <span style=\"font-style:italic\">X <span style=\"position: relative; bottom: 1.3ex; letter-spacing: -1.2ex; right: 1.2ex\">&#8594; displacement from the pump, as well as the kinetic and potential energy of the pump due to shaking forces. The finite elements model of the valve plate gasket has coherent results and the dynamic model of the pump provides various results for the analysis of the compressor vibration.

O Concreto Leve Estrutural com Pérolas de EPS (CLEPE), ou simplesmente Concreto com EPS, é uma alternativa na execução de lajes maciças. Como possui uma redução da ordem de 50% no peso próprio em relação ao Concreto Convencional (CC), suas características dinâmicas são diferentes. Neste trabalho descreve-se o comportamento dinâmico de lajes de CLEPE que são comparadas com as de CC por meio de ensaios dinâmicos e uma análise paramétrica. Nos ensaios dinâmicos focou-se a obtenção de três fatores imprescindíveis em uma análise dinâmica, que são as frequências naturais, os modos de vibração (deformadas modais) e o amortecimento estrutural, valor determinado experimentalmente que constitui dado de entrada em simulações numéricas. Os resultados experimentais indicam que o fator de amortecimento do CLEPE é ligeiramente maior que o do CC. Já os resultados da análise paramétrica revelam que a diminuição da rigidez é preponderante em relação à diminuição da massa do CLEPE, o que acarreta na diminuição das frequências naturais das lajes com este material. Mesmo com um amortecimento maior, as lajes de CLEPE apresentam maior sensibilidade às vibrações. Esta constatação, entretanto, não exclui o CLEPE como um material estrutural, apenas indica que, como no uso de qualquer material, as estruturas com CLEPE também devem ser verificadas com relação ao comportamento dinâmico. / The Structural Lightweight Concrete with EPS Beads (SLCEB), or simply EPS concrete, is an alternative in the execution of massive slabs. As it has a reduction in the order of 50% in self-weight in relation to the Ordinary Concrete (OC), its dynamic characteristics are different. In this work it is described the dynamic behavior of SLCEB slabs whose are compared with those of OC by means of dynamic tests and a parametric analysis. The obtainment of three essential factors in a dynamic analysis, which are natural frequencies, the ways of vibration (deformed modal), and the structural damping, experimentally determinate value which constitutes an input data in numerical simulations are focused in the dynamical tests. The experimental results indicate that the damping factor of SLCEB is a little bigger than the OC ones. Although, the results of the parametric analysis indicate that the decrease of stiffness is preponderant in relation to the decrease of the SLCEB mass, which result in some decrease of natural frequencies of slabs with this material. In despite of having a bigger damping, the SLCEB slabs expose a bigger sensibility to vibrations. However, this observation does not exclude the SLCEB as a structural material. It only means that as in use of any material, the SLCEB structures must be also verified in relation to the dynamic behavior.

Manipuladores robóticos com cinemática paralela apresentam alta rigidez, alta relação carga/peso próprio e boa precisão quando comparados a manipuladores de cinemática serial. No entanto, a região de trabalho dos manipuladores paralelos é limitada devido à presença de singularidade. Com o objetivo de aumentar a região de trabalho, redundâncias cinemáticas podem ser introduzidas nas cadeias cinemáticas. Devido à sua arquitetura paralela, a incerteza nos parâmetros geométricos pode ter grande influência no comportamento cinemático e no desempenho dinâmico. O estudo do impacto dessas incertezas quando redundâncias são introduzidas em uma manipulador robótico planar de cinemática paralela é o objetivo desse trabalho. Distribuições normais foram adotadas para a avaliação do comprimento dos elos. O impacto dessas variações foi avaliado numericamente através da comparação de resultados da simulação de trajetórias para os diferentes manipuladores robóticos. Além disso, verificou-se o impacto dessas variações nas regiões de singularidades dos sistemas robóticos. Essas avaliações numéricas foram realizadas para o manipulador robótico 3(P)RRR. Este manipulador consiste de 3 cadeias cinemáticas em paralelo. Cada cadeia apresenta uma junta prismática ativa (P), uma junta de revolução ativa (R) e duas juntas de revolução passivas (RR). Através desse trabalho, uma metodologia de avaliação do impacto de incerteza geométricas em manipuladores robóticos paralelos com redundância de atuação foi proposta e investigada. / Parallel kinematic manipulators present higher rigidity, better load capacity and improved accuracy when compared to serial kinematic manipulators. However, the workspace of parallel kinematic manipulator is usually limited due to the presence of singularity regions. In order to enlarge the workspace, kinematic redundancy can be introduced in the kinematic chains. Due to its parallel architecture, the uncertainty and variability of some geometric parameters may have great influence on its kinematic behavior and dynamic performance. The impact of these variabilities when redundancies are considered should also be verified. The aim of this study is to evaluate some geometric uncertainties in the links\' dimensions of a planar parallel robot manipulator with kinematic redundancy. Normal distributions are adopted for evaluating the variability of length of the links. The impact of these changes was evaluated numerically by comparing the results obtained by simulating trajectories for different robotic manipulators. In addition, the impact of these variabilities in the singularity regions is also assessed. These numerical evaluations have been performed for the redundant manipulator 3(P)RRR. This manipulator consists of three kinematic chains in parallel. Each chain has an active prismatic joint (P), an active revolute joint (R) and two passive revolute joints (RR). Through this work, a methodology for assessing the impact of geometric uncertainty in parallel robotic manipulators with kinematic redundancy has been proposed and investigated.

L'importance croissante de l'évaluation de la performance des structures soumis au chargement sismique souligne la nécessité d'estimer le risque de liquéfaction. Dans ce scénario extrême de la liquéfaction du sol, des conséquences dévastatrices sont observées, par exemple des tassements excessifs et des instabilités de pentes. Dans le cadre de cette thèse, la réponse dynamique et l'interaction d'un système ouvrage en terre-fondation sont étudiées, afin de déterminer quantitativement le mécanisme de ruine dû à la liquéfaction du sol de la fondation. Par ailleurs, les chargements sismiques peuvent induire dans les ouvrages en terre un mode de rupture générant des bandes de cisaillement. Une étude de sensibilité aux maillages a donc été engagée pour quantifier la dépendance des résultats de l'analyse dynamique. Par conséquent, l'utilisation d'une méthode de régularisation est évaluée au cours des analyses dynamiques. Le logiciel open-source Code_Aster, basé sur la méthode des Eléments Finis et développé par EDF R&D, est utilisé pour les simulations numériques, tandis que le comportement du sol est représenté par le modèle de comportement de l'ECP, développé à CentraleSupélec. En premier lieu, un modèle simplifié de propagation 1D des ondes SH dans une colonne de sol avec comportement hydromécanique couplé non linéaire a été simulé. L'effet des caractéristiques du signal sismique et de la perméabilité du sol sur la liquéfaction est évalué. Le signal sismique d'entrée est un élément important pour l'apparition de la liquéfaction, puisque la durée du choc principal peut conduire à de fortes non linéarités et à un état de liquéfaction étendu. En outre, quand une variation de perméabilité en fonction de l'état de liquéfaction est considérée, des changements significatifs sont observés pendant la phase de dissipation de la surpression interstitielle de l'eau et au comportement du matériau. En revanche, ces changements ne suivent pas une tendance unique. Puis, l'effet d'une méthode de régularisation avec cinématique enrichie, appelée premier gradient de dilatation, sur la propagation des ondes SH est étudié au travers d'une solution analytique. Des problèmes à la réponse dynamique du sol sont observés et discutés quand cette méthode de régularisation est appliquée. Ensuite, un modèle 2D d'un déblai est simulé et sa réponse dynamique est évaluée en conditions sèches, complètement drainées et hydromécanique couplées. Deux critères sont utilisés pour définir le début de la rupture de la structure. Le travail du second ordre est utilisé pour décrire l'instabilité locale à des instants spécifiques du mouvement sismique, tandis que l'estimation d'un facteur de sécurité locale est proposée prenant en compte la résistance résiduelle du sol. En ce qui concerne le mode de ruine, l'effet de la surpression interstitielle de l'eau est de grande importance, puisqu'un déblai stable en conditions sèches et complètement drainées, devient instable lors de l'analyse couplée à cause de la liquéfaction de la fondation. Enfin, un système digue-fondation est simulé et l'influence de la perméabilité du sol, la profondeur de la couche liquéfiable, ainsi que, les caractéristiques du séisme sur la ruine induite par la liquéfaction du sol est évaluée. Pour ce modèle de digue, le niveau de dommages est fortement lié à la fois à l'apparition de la liquéfaction dans la fondation et la dissipation de la surpression d'eau. Une surface d'effondrement circulaire est générée à l'intérieur de la couche du sol liquéfié et se propage vers la crête dans les deux côtés de la digue. Pourtant, lorsque la couche liquéfiée est située en profondeur, la digue n'est pas affectée par la liquéfaction de la fondation pour ce cas particulier de chargement. Ce travail de recherche se concentre sur une étude de cas de référence pour l'évaluation sismique des ouvrages en terre soumis à un séisme et fournit des méthodes et outils de calculs numériques performants accessibles aux ingénieurs. / The increasing importance of performance-based earthquake engineering analysis points out the necessity to assess quantitatively the risk of liquefaction. In this extreme scenario of soil liquefaction, devastating consequences are observed, e.g. excessive settlements, lateral spreading and slope instability. The present PhD thesis discusses the global dynamic response and interaction of an earth structure-foundation system, so as to determine quantitatively the collapse mechanism due to foundation’s soil liquefaction. As shear band generation is a potential earthquake-induced failure mode in such structures, the FE mesh dependency of results of dynamic analyses is thoroughly investigated and an existing regularization method is evaluated. The open-source FE software developed by EDF R&D, called Code_Aster is used for the numerical simulations, while soil behavior is represented by the ECP constitutive model, developed at CentraleSupélec. Starting from a simplified model of 1D SH wave propagation in a soil column with coupled hydromechanical nonlinear behavior, the effect of seismic hazard and soil’s permeability on liquefaction is assessed. Input ground motion is a key component for soil liquefaction apparition, as long duration of mainshock can lead to important nonlinearity and extended soil liquefaction. Moreover, when a variation of permeability as function of liquefaction state is considered, changes in the dissipation phase of excess pore water pressure and material behavior are observed, which do not follow a single trend. The effect of a regularization method with enhanced kinematics approach, called first gradient of dilation model, on 1D SH wave propagation is studied through an analytical solution. Deficiencies of the use of this regularization method are observed and discussed, e.g. spurious waves apparition in the soil’s seismic response. Next, a 2D embankment-type model is simulated and its dynamic response is evaluated in dry, fully drained and coupled hydromechanical conditions. Two criteria are used to define the onset of the structure’s collapse. The second order work is used to describe the local instability at specific instants of the ground motion, while the estimation of a local safety factor is proposed by calculating soil’s residual strength. Concerning the failure mode, the effect of excess pore water pressure is of great importance, as an otherwise stable structure-foundation system in dry and fully drained conditions becomes unstable during coupled analysis. Finally, a levee- foundation system is simulated and the influence of soil’s permeability, depth of the liquefiable layer, as well as, characteristics of input ground motion on the liquefaction-induced failure is evaluated. For the current levee model, its induced damage level (i.e. settlements and deformations) is strongly related to both liquefaction apparition and dissipation of excess pore water pressure on the foundation. A circular collapse surface is generated inside the liquefied region and extends towards the crest in both sides of the levee. Even so, when the liquefied layer is situated in depth, no effect on the levee response is found. This research work can be considered as a reference case study for seismic assessment of embankment-type structures subjected to earthquake and provides a high-performance computational framework accessible to engineers.

Actuellement, la restauration des oeuvres d’art, notamment des statues fracturées, repose sur des techniqueséprouvées, mais empiriques. Les statues endommagées comportent souvent des parties brisées. Leur restaurationconsiste la plupart du temps à les rassembler. Ainsi apparait la nécessité de prendre en compte lespropriétés mécaniques des interfaces entre les différentes parties brisées, ce qui permet de limiter l’ampleur desréparations et ainsi, de mieux conserver l’intégrité de l’oeuvre. Par ailleurs, les techniques numériques d’acquisition3D font leur entrée au service de la conservation du patrimoine. Cette thèse propose une méthodologiecapable d’utiliser des données issues d’une acquisition 3D pour simuler les opérations de restauration et leurseffets sur la structure de l’oeuvre. Les processus de restauration peuvent ainsi être testés et optimisés.Un scanner laser est utilisé pour l’acquisition de la géométrie des oeuvres, ce qui nous permet de reconstruireun modèle 3D pour la simulation numérique. Les calculs sont menés dans le cadre de la mécanique des milieuxcontinus déformables avec FLAC3D. Pour vérifier tous les points clés garantissant la stabilité mécanique, lecomportement des éléments de renforts et celui des interfaces entre les blocs ont été considérés. À partirdes résultats de ces études, une critique des stratégies de restauration mises en oeuvre ou envisageables estproposée.De plus, plusieurs méthodes de caractérisation visant à retrouver la provenance du matériau et/ou estimerles propriétés mécaniques de l’oeuvre sont proposées : caractérisations physico-chimiques et minéralogiques,essais non destructifs et destructifs. Une campagne expérimentale visant à caractériser le comportement desfractures en contact frottant avec acquisition de l’état de surface a été réalisée. Une analyse des corrélationsentre les propriétés mécaniques et morphologique des interfaces est ensuite élaborée. Enfin nous proposonsdes modèles prédictifs construits par régressions linéaires multiples et multivariées. Cette étude permet desimuler le comportement d’une oeuvre fracturée. / Currently, the artworks restoration, including broken statues, are based on proven but empirical techniques. Damaged statues often have broken parts. Restoration mainly consists in joining these parts. Thus appears the necessity of taking into account the interfaces mechanical properties between the different broken parts, reducing thereby the extent of repairs and thus better maintain the integrity of the work. Beside this, digital 3D acquisition techniques become more and more popular among the cultural heritage community. This thesis proposes a methodology able to use 3D acquisition datas to simulate the restoration operations and their effects on the structure. The restoration strategy can thus be tested and optimized. A laser scanner is used to acquire the statue geometry, allowing to reconstruct a 3D model for numerical simulation. Computations are carried out within the framework of deformable continuum mechanics using the FLAC3D software. In order to check all the key points ensuring mechanical stability, the behavior of reinforcing elements and those of the interfaces between blocks were considered. From the results of the present studies, a critical analysis of implemented or possible restoration strategy is proposed. In addition, several characterization methods to find the material origin and/or estimate the mechanical properties of the work are proposed : physico-chemical and mineralogical characterizations, non-destructive and destructive tests. An experimental campaign to characterize the behavior of fractures in contact with surface acquisition was performed. An analysis of correlations between mechanical and morphological interfaces properties is then developed. Finally, we propose a predictive modelling based on multiple linear and multivariate regressions. This study allow the simulation of fractured artworks behaviour.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Atualmente, os projetos de edifícios altos necessitam cada vez mais de sistemas estruturais simples, que agilizem sua montagem, reduzindo os custos e promovendo maior flexibilidade de utilização para os espaços construídos. Com essa finalidade, estruturas com poucas vigas vêm sendo muito utilizadas. Entretanto, o sistema estrutural com poucas vigas pode ocasionar dois tipos de problemas, relacionados entre si, a saber: diminuição do sistema de contraventamento da edificação e vibrações excessivas. Portanto, é fundamental, nesses casos, a verificação da estabilidade global da estrutura, utilizando índices de sensibilidade além de outros parâmetros de projeto, como também, o desenvolvimento de um estudo minucioso acerca do conforto humano da edificação. Assim sendo, neste trabalho de pesquisa foram investigados quatro modelos estruturais de edifícios altos de concreto armado, com base no estudo da variação entre o número de pavimentos e a quantidade de vigas existentes em cada modelo, objetivando-se verificar quais os efeitos que tais variações podem vir a gerar sobre a estabilidade global e, bem como, sobre o conforto humano dos sistemas estruturais investigados. A modelagem numérica dos edifícios em estudo foi realizada através do emprego do programa ANSYS e, para tal, foram utilizadas técnicas básicas de discretização, por meio do método dos elementos finitos. As conclusões alcançadas ao longo da investigação versam acerca do estudo da resposta estrutural estática e dinâmica dos edifícios, no que diz respeito as variações dos valores dos parâmetros de instabilidade, dos valores dos deslocamentos e esforços, e, bem como, dos níveis de conforto humano de cada modelo estrutural analisado. / Currently, the tall buildings projects increasingly need a simple structural systems that streamline their assembly, reducing costs and promoting greater flexibility of use for the built environment. For this purpose, structures with few beams are being widely used. However, the structural system with few beams may cause two kinds of problems, related to each other, namely: reduction of the bracing system of the building and excessive vibration. It is therefore vital in such cases, the verification of global stability of the structure, using sensitivity indexes and other design parameters, as well as the development of a thorough study of the human comfort of the building. Therefore, this research work have been investigated four structural models of tall buildings of reinforced concrete, based on the study of the variation of the number of floors and the quantity of beams in each model, aiming to verify what effects these variations. They are likely to generate on the overall stability and, as well as on human comfort and structural systems investigated. The numerical modeling of buildings under study was performed by employing the ANSYS program, and to such basic techniques of discretization were used through the finite element method. The conclusions reached during the investigation turn concerning the study of the static and dynamic structural response of buildings in respect of the variations of the values of the instability criteria, of the values of displacements and efforts, and as well, the human comfort level each structural model analyzed.

Les maladies cardiovasculaires représentent un important problème de santé publique à travers le monde. Parmi ces pathologies, l’infarctus du myocarde (IM) a fait l’objet de nombreux essais visant à diminuer sa sévérité. Néanmoins peu ont remporté leur pari. Cet échec peut avoir plusieurs composantes parmi lesquelles la méconnaissance de la complexité des mécanismes moléculaires impliqués. Notre compréhension de l’IM a cependant été nettement améliorée grâce à des méthodes utilisées pendant les dernières décennies et qui consistaient à étudier séparément un nombre limité d’acteurs moléculaires impliqués dans un mécanisme simple et linéaire. Cependant, l’échec des essais cliniques basés sur ces approches réductionnistes ont montré leurs limites. L’émergence de la biologie des systèmes, ces dernières années, a stimulé les recherches visant à mieux intégrer et comprendre la nature complexe et stochastique des réseaux moléculaires et leur dynamique dans la progression des pathologies. L’objectif général de cette thèse a consisté en le développement et l’amélioration de méthode d’analyses et de combinaison des données spatio-temporelles issus d’expériences réalisées sur un modèle d’infarctus du myocarde chez la souris. L’objectif scientifique visait à caractériser les principaux signaux dynamiques au cours de la séquence d’ischémie-reperfusion. A cet effet, nous avons tout d’abord développé une chaîne de méthode utilisant la clarification d’organe et la microscopie de fluorescence permettant de quantifier, en 3 dimensions, la zone du myocarde soumise au choc oxydant lors de la reperfusion. Dans une seconde partie, nous avons développé une nouvelle chaîne analytique pour caractériser la dynamique d’expression des transcrits. Appliquée aux animaux contrôles (soumis à la chirurgie et l’anesthésie), nous mettrons, grâce à cette chaîne de méthode, le rôle majeur de la voie de l’interleukine 6 dans le développement de la réponse immunitaire et nous concluons ainsi sur la nécessité de réaliser une analyse dynamique du modèle expérimental pour caractériser sa réponse à l’échelle moléculaire et éviter toute surinterprétation de la réponse à l’IM / Cardiovascular diseases represent a major health burden worldwide. According to the World Health Organization, 17 million people are dying each year by heart diseases which account to 31% of total deaths globally. Among these diseases is myocardial infarction (MI). Several efforts have been made to decrease the associated mortality rates but unfortunately, only few has succeeded to date. This failure is contributed to several factors, among them is the misunderstanding of the mechanism responsible for the progression of the disease.Our understanding of the MI pathology has been greatly improved by the approaches that have been widely used in the previous decades, relying mainly on studying molecules/pathways separately. However, this knowledge was not enough to make a difference clinically. Therefore, deciphering the interconnections between molecules has become an urge for better understanding of the diseases’ progression. In this regard, the work in this doctoral thesis involves different aspects of the MI pathology. The general aim of this work is to improve the dynamic analytical approach using systems biology tools, where new mechanistic information is decoded. Firstly, in a 3D heart model, we propose a chain of methods using clarified mouse heart and fluorescence microscopy to molecularly characterize the area at risk in the myocardium of IR and cardioprotected mice based on its redox state. In addition, we aim to develop a new analytical approach using dynamical large-scale transcriptomic data for characterizing the dynamic transcripts expression. Applying this approach on a control mouse model (mice subjected to anesthesia and surgical interventions), we show that Il-6 is a major mediator of the activated inflammatory reaction. In conclusion, this analytical approach highlights the necessity of the sapatio-temporal analysis to characterize the molecular events occurring in response to MI

<p>The performance of different types of nebulisers: Vulkan direct injection nebuliser (Vulkan DIN), direct injection high efficiency nebuliser (DIHEN), microconcentric nebuliser coupled to cyclonic or double pass spray chamber (MCN-C or MCN-DP, respectively) was investigated and compared when used for sample introduction to ICP-MS or ICP-OES. With ICP-OES, in axial viewing mode, intensity distributions across the radius of the plasma (radial intensity profiles) were determined for different spectral lines with Esum 1.85-15.41 eV to determine fundamental plasma properties for various matrices using Vulkan DIN and MCN-C. The results showed that with the MCN-C the ionisation temperature (Tion) was about the same across the measured region of the plasma (±3.0 mm) whereas with the Vulkan DIN the Tion was significantly lower in the centre of the plasma. A large deviation from local thermodynamic equilibrium, as well as deteriorated stability, was observed for the plasma when using the Vulkan DIN.</p><p>With ICP-MS noise power spectra (NPS) were generated to identify sources of noise. NPS showed that the magnitude of white noise for the tested sample introduction systems decreased in the following order: Vulkan DIN > DIHEN > MCN-C > MCN-DP. This order follows the decrease of mean droplet size and span of the size distribution, indicating that the white noise is caused by spatial and temporal non-uniform desolvation and ionisation. Another source of noise arose from the peristaltic pump and the magnitude of pump interference noise decreased in the following order: DIHEN > MCN-C/DP > Vulkan DIN. Mains power interference noise and 1/f noise were lower for the direct injection nebulisers compared to the spray chamber systems. The contribution or effects of these noise components on relative standard deviations of steady-state ion-count rate and isotope ratio measurements is discussed in this thesis.</p><p>Aerosols generated by the Vulkan DIN and the DIHEN were also directly characterised using Particle Dynamic Analysis. The Vulkan DIN produced particles with a mean diameter of ~30 µm and a size distribution between 2-80 µm. With the DIHEN the corresponding values were ~11 µm and 1-40 µm, respectively, with a few particles at 55-78 µm. The mean velocity of particles from the Vulkan DIN was ~10 m s-1 and from the DIHEN ~18 m s-1. The lower velocity allows longer residence time counteracting the effects of the larger droplet size.</p>

The performance of different types of nebulisers: Vulkan direct injection nebuliser (Vulkan DIN), direct injection high efficiency nebuliser (DIHEN), microconcentric nebuliser coupled to cyclonic or double pass spray chamber (MCN-C or MCN-DP, respectively) was investigated and compared when used for sample introduction to ICP-MS or ICP-OES. With ICP-OES, in axial viewing mode, intensity distributions across the radius of the plasma (radial intensity profiles) were determined for different spectral lines with Esum 1.85-15.41 eV to determine fundamental plasma properties for various matrices using Vulkan DIN and MCN-C. The results showed that with the MCN-C the ionisation temperature (Tion) was about the same across the measured region of the plasma (±3.0 mm) whereas with the Vulkan DIN the Tion was significantly lower in the centre of the plasma. A large deviation from local thermodynamic equilibrium, as well as deteriorated stability, was observed for the plasma when using the Vulkan DIN. With ICP-MS noise power spectra (NPS) were generated to identify sources of noise. NPS showed that the magnitude of white noise for the tested sample introduction systems decreased in the following order: Vulkan DIN &gt; DIHEN &gt; MCN-C &gt; MCN-DP. This order follows the decrease of mean droplet size and span of the size distribution, indicating that the white noise is caused by spatial and temporal non-uniform desolvation and ionisation. Another source of noise arose from the peristaltic pump and the magnitude of pump interference noise decreased in the following order: DIHEN &gt; MCN-C/DP &gt; Vulkan DIN. Mains power interference noise and 1/f noise were lower for the direct injection nebulisers compared to the spray chamber systems. The contribution or effects of these noise components on relative standard deviations of steady-state ion-count rate and isotope ratio measurements is discussed in this thesis. Aerosols generated by the Vulkan DIN and the DIHEN were also directly characterised using Particle Dynamic Analysis. The Vulkan DIN produced particles with a mean diameter of ~30 µm and a size distribution between 2-80 µm. With the DIHEN the corresponding values were ~11 µm and 1-40 µm, respectively, with a few particles at 55-78 µm. The mean velocity of particles from the Vulkan DIN was ~10 m s-1 and from the DIHEN ~18 m s-1. The lower velocity allows longer residence time counteracting the effects of the larger droplet size.