The work consists of two parts. In the first part which is concerned with random walks, we construct the conditional versions of a multidimensional random walk given that it does not leave the Weyl chambers of type C and of type D, respectively, in terms of a Doob h-transform. Furthermore, we prove functional limit theorems for the rescaled random walks. This is an extension of recent work by Eichelsbacher and Koenig who studied the analogous conditioning for the Weyl chamber of type A. Our proof follows recent work by Denisov and Wachtel who used martingale properties and a strong approximation of random walks by Brownian motion. Therefore, we are able to keep minimal moment assumptions. Finally, we present an alternate function that is amenable to an h-transform in the Weyl chamber of type C. In the second part which is concerned with Brownian motion, we examine the non-exit probability of a multidimensional Brownian motion from a growing truncated Weyl chamber. Different regimes are identified according to the growth speed, ranging from polynomial decay over stretched-exponential to exponential decay. Furthermore we derive associated large deviation principles for the empirical measure of the properly rescaled and transformed Brownian motion as the dimension grows to infinity. Our main tool is an explicit eigenvalue expansion for the transition probabilities before exiting the truncated Weyl chamber.

[pt] As doenças trasmitidas pelo sangue, assim como a necessidade de bancos de sangue para um pronto auxílio em casos de acidentes tem estimulado esforços para desenvolver substitutos do sangue. A albumina serica humana (HSA do ingles Human Serum Albumin) é a proteína mais abundante no plasma sanguíneo. A molécula heme é a transportadora de oxigênio no sangue. Portanto, um estudo detalhado da interação HSA/heme seria útil em pesquisas que visam tornar o complexo HSA-heme em um substituto do sangue. Nesta tese, foram usadas técnicas de dinâmica molecular e ferramentas estatísticas para estudar o sistema HSA-heme em solvente explícito. Tanto o ligante quanto a proteína foram também estudados separadamente em meio aquoso. Dentre outros resultados, nosso estudo revelou a organização da água circundante, os efeitos da ligação do heme na HSA, os mecanismos moleculares da ligação do heme, os movimentos coletivos da proteína livre e ligada, assim como também os aminoácidos que atuam como dobradiças moleculares na mudança conformacional que sofre a proteína ao ligar o heme. / [en] Diseases transmitted through the blood, as well as the need for blood banks to help in case of accidents, stimulated efforts to develop blood substitutes. The human serum albumin (HSA) is the most abundant protein in blood plasma. The heme molecule is the carrier of oxygen in the blood. Therefore, a detailed study of the interaction HSA/heme could give useful insights in the research aimed to convert the HSA-heme complex into a blood substitute. In this thesis, molecular dynamics techniques and statistical tools were applied to study the HSA-heme system in explicit solvent. Both ligand and protein were also studied separately in aqueous medium. Among other results, our study reveals the organization of the surrounding water, the effects of the heme upon its binding to HSA, the molecular mechanisms for heme binding, the collective motions of the protein with and without the heme, as well as the amino acids that act as molecular hinges in the conformational change between the free and bound forms of the protein.

L'athérosclérose est une maladie vasculaire complexe qui affecte la paroi des artères (par l'épaississement) et les lumières (par la formation de plaques). La rupture d'une plaque de l'artère carotide peut également provoquer un accident vasculaire cérébral ischémique et des complications. Bien que plusieurs modalités d'imagerie médicale soient actuellement utilisées pour évaluer la stabilité d'une plaque, elles présentent des limitations telles que l'irradiation, les propriétés invasives, une faible disponibilité clinique et un coût élevé. L'échographie est une méthode d'imagerie sûre qui permet une analyse en temps réel pour l'évaluation des tissus biologiques. Il est intéressant et prometteur d’appliquer une échographie vasculaire pour le dépistage et le diagnostic précoces des plaques d’artère carotide. Cependant, les ultrasons vasculaires actuels identifient uniquement la morphologie d'une plaque en termes de luminosité d'écho ou l’impact de cette plaque sur les caractéristiques de l’écoulement sanguin, ce qui peut ne pas être suffisant pour diagnostiquer l’importance de la plaque. La technique d’élastographie vasculaire non-intrusive (« noninvasive vascular elastography (NIVE) ») a montré le potentiel de détermination de la stabilité d'une plaque. NIVE peut déterminer le champ de déformation de la paroi vasculaire en mouvement d’une artère carotide provoqué par la pulsation cardiaque naturelle. En raison des différences de module de Young entre les différents tissus des vaisseaux, différents composants d’une plaque devraient présenter différentes déformations, caractérisant ainsi la stabilité de la plaque. Actuellement, les performances et l’efficacité numérique sous-optimales limitent l’acceptation clinique de NIVE en tant que méthode rapide et efficace pour le diagnostic précoce des plaques vulnérables. Par conséquent, il est nécessaire de développer NIVE en tant qu’outil d’imagerie non invasif, rapide et économique afin de mieux caractériser la vulnérabilité liée à la plaque. La procédure à suivre pour effectuer l’analyse NIVE consiste en des étapes de formation et de post-traitement d’images. Cette thèse vise à améliorer systématiquement la précision de ces deux aspects de NIVE afin de faciliter la prédiction de la vulnérabilité de la plaque carotidienne. Le premier effort de cette thèse a été dédié à la formation d'images (Chapitre 5). L'imagerie par oscillations transversales a été introduite dans NIVE. Les performances de l’imagerie par oscillations transversales couplées à deux estimateurs de contrainte fondés sur un modèle de déformation fine, soit l’ « affine phase-based estimator (APBE) » et le « Lagrangian speckle model estimator (LSME) », ont été évaluées. Pour toutes les études de simulation et in vitro de ce travail, le LSME sans imagerie par oscillation transversale a surperformé par rapport à l'APBE avec imagerie par oscillations transversales. Néanmoins, des estimations de contrainte principales comparables ou meilleures pourraient être obtenues avec le LSME en utilisant une imagerie par oscillations transversales dans le cas de structures tissulaires complexes et hétérogènes. Lors de l'acquisition de signaux ultrasonores pour la formation d'images, des mouvements hors du plan perpendiculaire au plan de balayage bidimensionnel (2-D) existent. Le deuxième objectif de cette thèse était d'évaluer l'influence des mouvements hors plan sur les performances du NIVE 2-D (Chapitre 6). À cette fin, nous avons conçu un dispositif expérimental in vitro permettant de simuler des mouvements hors plan de 1 mm, 2 mm et 3 mm. Les résultats in vitro ont montré plus d'artefacts d'estimation de contrainte pour le LSME avec des amplitudes croissantes de mouvements hors du plan principal de l’image. Malgré tout, nous avons néanmoins obtenu des estimations de déformations robustes avec un mouvement hors plan de 2.0 mm (coefficients de corrélation supérieurs à 0.85). Pour un jeu de données cliniques de 18 participants présentant une sténose de l'artère carotide, nous avons proposé d'utiliser deux jeux de données d'analyses sur la même plaque carotidienne, soit des images transversales et longitudinales, afin de déduire les mouvements hors plan (qui se sont avérés de 0.25 mm à 1.04 mm). Les résultats cliniques ont montré que les estimations de déformations restaient reproductibles pour toutes les amplitudes de mouvement, puisque les coefficients de corrélation inter-images étaient supérieurs à 0.70 et que les corrélations croisées normalisées entre les images radiofréquences étaient supérieures à 0.93, ce qui a permis de démontrer une plus grande confiance lors de l'analyse de jeu de données cliniques de plaques carotides à l'aide du LSME. Enfin, en ce qui concerne le post-traitement des images, les algorithmes NIVE doivent estimer les déformations des parois des vaisseaux à partir d’images reconstituées dans le but d’identifier les tissus mous et durs. Ainsi, le dernier objectif de cette thèse était de développer un algorithme d'estimation de contrainte avec une résolution de la taille d’un pixel ainsi qu'une efficacité de calcul élevée pour l'amélioration de la précision de NIVE (Chapitre 7). Nous avons proposé un estimateur de déformation de modèle fragmenté (SMSE) avec lequel le champ de déformation dense est paramétré avec des descriptions de transformées en cosinus discret, générant ainsi des composantes de déformations affines (déformations axiales et latérales et en cisaillement) sans opération mathématique de dérivées. En comparant avec le LSME, le SMSE a réduit les erreurs d'estimation lors des tests de simulations, ainsi que pour les mesures in vitro et in vivo. De plus, la faible mise en oeuvre de la méthode SMSE réduit de 4 à 25 fois le temps de traitement par rapport à la méthode LSME pour les simulations, les études in vitro et in vivo, ce qui pourrait permettre une implémentation possible de NIVE en temps réel. / Atherosclerosis is a complex vascular disease that affects artery walls (by thickening) and lumens (by plaque formation). The rupture of a carotid artery plaque may also induce ischemic stroke and complications. Despite the use of several medical imaging modalities to evaluate the stability of a plaque, they present limitations such as irradiation, invasive property, low clinical availability and high cost. Ultrasound is a safe imaging method with a real time capability for assessment of biological tissues. It is clinically used for early screening and diagnosis of carotid artery plaques. However, current vascular ultrasound technologies only identify the morphology of a plaque in terms of echo brightness or the impact of the vessel narrowing on flow properties, which may not be sufficient for optimum diagnosis. Noninvasive vascular elastography (NIVE) has been shown of interest for determining the stability of a plaque. Specifically, NIVE can determine the strain field of the moving vessel wall of a carotid artery caused by the natural cardiac pulsation. Due to Young’s modulus differences among different vessel tissues, different components of a plaque can be detected as they present different strains thereby potentially helping in characterizing the plaque stability. Currently, sub-optimum performance and computational efficiency limit the clinical acceptance of NIVE as a fast and efficient method for the early diagnosis of vulnerable plaques. Therefore, there is a need to further develop NIVE as a non-invasive, fast and low computational cost imaging tool to better characterize the plaque vulnerability. The procedure to perform NIVE analysis consists in image formation and image post-processing steps. This thesis aimed to systematically improve the accuracy of these two aspects of NIVE to facilitate predicting carotid plaque vulnerability. The first effort of this thesis has been targeted on improving the image formation (Chapter 5). Transverse oscillation beamforming was introduced into NIVE. The performance of transverse oscillation imaging coupled with two model-based strain estimators, the affine phase-based estimator (APBE) and the Lagrangian speckle model estimator (LSME), were evaluated. For all simulations and in vitro studies, the LSME without transverse oscillation imaging outperformed the APBE with transverse oscillation imaging. Nonetheless, comparable or better principal strain estimates could be obtained with the LSME using transverse oscillation imaging in the case of complex and heterogeneous tissue structures. During the acquisition of ultrasound signals for image formation, out-of-plane motions which are perpendicular to the two-dimensional (2-D) scan plane are existing. The second objective of this thesis was to evaluate the influence of out-of-plane motions on the performance of 2-D NIVE (Chapter 6). For this purpose, we designed an in vitro experimental setup to simulate out-of-plane motions of 1 mm, 2 mm and 3 mm. The in vitro results showed more strain estimation artifacts for the LSME with increasing magnitudes of out-of-plane motions. Even so, robust strain estimations were nevertheless obtained with 2.0 mm out-of-plane motion (correlation coefficients higher than 0.85). For a clinical dataset of 18 participants with carotid artery stenosis, we proposed to use two datasets of scans on the same carotid plaque, one cross-sectional and the other in a longitudinal view, to deduce the out-of-plane motions (estimated to be ranging from 0.25 mm to 1.04 mm). Clinical results showed that strain estimations remained reproducible for all motion magnitudes since inter-frame correlation coefficients were higher than 0.70, and normalized cross-correlations between radiofrequency images were above 0.93, which indicated that confident motion estimations can be obtained when analyzing clinical dataset of carotid plaques using the LSME. Finally, regarding the image post-processing component of NIVE algorithms to estimate strains of vessel walls from reconstructed images with the objective of identifying soft and hard tissues, we developed a strain estimation method with a pixel-wise resolution as well as a high computation efficiency for improving NIVE (Chapter 7). We proposed a sparse model strain estimator (SMSE) for which the dense strain field is parameterized with Discrete Cosine Transform descriptions, thereby deriving affine strain components (axial and lateral strains and shears) without mathematical derivative operations. Compared with the LSME, the SMSE reduced estimation errors in simulations, in vitro and in vivo tests. Moreover, the sparse implementation of the SMSE reduced the processing time by a factor of 4 to 25 compared with the LSME based on simulations, in vitro and in vivo results, which is suggesting a possible implementation of NIVE in real time.

The work consists of two parts. In the first part which is concerned with random walks, we construct the conditional versions of a multidimensional random walk given that it does not leave the Weyl chambers of type C and of type D, respectively, in terms of a Doob h-transform. Furthermore, we prove functional limit theorems for the rescaled random walks. This is an extension of recent work by Eichelsbacher and Koenig who studied the analogous conditioning for the Weyl chamber of type A. Our proof follows recent work by Denisov and Wachtel who used martingale properties and a strong approximation of random walks by Brownian motion. Therefore, we are able to keep minimal moment assumptions. Finally, we present an alternate function that is amenable to an h-transform in the Weyl chamber of type C. In the second part which is concerned with Brownian motion, we examine the non-exit probability of a multidimensional Brownian motion from a growing truncated Weyl chamber. Different regimes are identified according to the growth speed, ranging from polynomial decay over stretched-exponential to exponential decay. Furthermore we derive associated large deviation principles for the empirical measure of the properly rescaled and transformed Brownian motion as the dimension grows to infinity. Our main tool is an explicit eigenvalue expansion for the transition probabilities before exiting the truncated Weyl chamber.

A major concern for geotechnical engineers is the ability to predict how a soil will react to large ground motions produced by earthquakes. Of all the different types of soil, liquefiable soils present some of the greatest challenges. The ability to quantify the degradation of a soil's shear modulus as it undergoes liquefaction would help engineers design more reliably and economically. This thesis uses ground motions recorded by an array of downhole accelerometers on Port Island, Japan, during the 1995 Kobe Earthquake, to quantify the shear modulus of sand as it liquefies. It has been shown that the shear modulus of sand decreases significantly as it liquefies, apparently decreasing in proportion to the increasing excess pore water pressure ratio (Ru). When completely liquefied, the shear modulus of sand (Ru = 1.0) for a relative density of 40 to 50% is approximately 15% of the high-strain modulus of the sand in its non-liquefied state, or 1% of its initial low-strain value. Presented in this thesis is an approach to modeling the shear modulus degradation of sand as it liquefies. This approach, called the "degrading shear modulus backbone curve method" reasonably predicts the hysteretic shear stress behavior of the liquefied sand. The shear stresses and ground accelerations computed using this method reasonably matches those recorded at the Port Island Downhole Array (PIDA) site. The degrading shear modulus backbone method is recommended as a possible method for conducting ground response analyses at sites with potentially liquefiable soils.

Les systèmes et matériaux mécaniques non linéaires sont largement utilisés dans divers domaines. Cependant, leur modélisation et leur conception ne sont pas triviales car elles nécessitent une compréhension complète de leurs non-linéarités internes et d'autres phénomènes. Pour permettre une conception efficace, nous devons d'abord introduire des modèles de calcul afin de caractériser avec précision leur comportement complexe. En outre, de nouvelles techniques de conception inverse sont également nécessaires pour comprendre comment le comportement change lorsque nous modifions les paramètres de conception des systèmes mécaniques non linéaires et des matériaux. Par conséquent, dans cette thèse, nous présentons trois nouvelles méthodes pour la modélisation informatique et la conception de systèmes mécaniques non linéaires et de matériaux. Dans le premier article, nous abordons le problème de la conception de systèmes mécaniques non linéaires présentant des mouvements périodiques stables en réponse à une force périodique. Nous présentons une méthode de calcul qui utilise une approche du domaine fréquentiel pour la simulation dynamique et la puissante analyse de sensibilité pour l'optimisation de la conception afin de concevoir des systèmes mécaniques conformes avec des oscillations de grande amplitude. Notre méthode est polyvalente et peut être appliquée à divers types de systèmes mécaniques souples. Nous validons son efficacité en fabriquant et en évaluant plusieurs prototypes physiques. Ensuite, nous nous concentrons sur la modélisation informatique et la caractérisation mécanique des matériaux non linéaires dominés par le contact, en particulier les matériaux à emboîtement discret (DIM), qui sont des tissus de cotte de mailles généralisés constitués d'éléments d'emboîtement quasi-rigides. Contrairement aux matériaux élastiques conventionnels pour lesquels la déformation et la force de rappel sont directement couplées, la mécanique des DIM est régie par des contacts entre des éléments individuels qui donnent lieu à des contraintes de déformation cinématique anisotrope. Pour reproduire le comportement biphasique du DIM sans simuler des structures à micro-échelle coûteuses, nous introduisons une méthode efficace de limitation de la déformation anisotrope basée sur la programmation conique du second ordre (SOCP). En outre, pour caractériser de manière exhaustive la forte anisotropie, le couplage complexe et d'autres phénomènes non linéaires du DIM, nous introduisons une nouvelle approche d'homogénéisation pour distiller des limites de déformation à grande échelle à partir de simulations à micro-échelle et nous développons un modèle macromécanique basé sur des données pour simuler le DIM avec des contraintes de déformation homogénéisées. / Nonlinear mechanical systems and materials are broadly used in diverse fields. However, their modeling and design are nontrivial as they require a complete understanding of their internal nonlinearities and other phenomena. To enable their efficient design, we must first introduce computational models to accurately characterize their complex behavior. Furthermore, new inverse design techniques are also required to capture how the behavior changes when we change the design parameters of nonlinear mechanical systems and materials. Therefore, in this thesis, we introduce three novel methods for computational modeling and design of nonlinear mechanical systems and materials. In the first article, we address the design problem of nonlinear mechanical systems exhibiting stable periodic motions in response to a periodic force. We present a computational method that utilizes a frequency-domain approach for dynamical simulation and the powerful sensitivity analysis for design optimization to design compliant mechanical systems with large-amplitude oscillations. Our method is versatile and can be applied to various types of compliant mechanical systems. We validate its effectiveness by fabricating and evaluating several physical prototypes. Next, we focus on the computation modeling and mechanical characterization of contact-dominated nonlinear materials, particularly Discrete Interlocking Materials (DIM), which are generalized chainmail fabrics made of quasi-rigid interlocking elements. Unlike conventional elastic materials for which deformation and restoring forces are directly coupled, the mechanics of DIM are governed by contacts between individual elements that give rise to anisotropic kinematic deformation constraints. To replicate the biphasic behavior of DIM without simulating expensive microscale structures, we introduce an efficient anisotropic strain-limiting method based on second-order cone programming (SOCP). Additionally, to comprehensively characterize strong anisotropy, complex coupling, and other nonlinear phenomena of DIM, we introduce a novel homogenization approach for distilling macroscale deformation limits from microscale simulations and develop a data-driven macromechanical model for simulating DIM with homogenized deformation constraints.

Depuis l’article fondateur de Jordan, Kinderlehrer et Otto en 1998, il est bien connu qu’une large classe d’équations paraboliques peuvent être vues comme des flots de gradient dans l’espace de Wasserstein. Le but de cette thèse est d’étendre cette théorie à certaines équations et systèmes qui n’ont pas exactement une structure de flot de gradient. Les interactions étudiées sont de différentes natures. Le premier chapitre traite des systèmes avec des interactions non locales dans la dérive. Nous étudions ensuite des systèmes de diffusions croisées s’appliquant aux modèles de congestion pour plusieurs populations. Un autre modèle étudié est celui où le couplage se trouve dans le terme de réaction comme les systèmes proie-prédateur avec diffusion ou encore les modèles de croissance tumorale. Nous étudierons enfin des systèmes de type nouveau où l’interaction est donnée par un problème de transport multi-marges. Une grande partie de ces problèmes est illustrée de simulations numériques. / Since 1998 and the seminal work of Jordan, Kinderlehrer and Otto, it is well known that a large class of parabolic equations can be seen as gradient flows in the Wasserstein space. This thesis is devoted to extensions of this theory to equations and systems which do not have exactly a gradient flow structure. We study different kind of couplings. First, we treat the case of nonlocal interactions in the drift. Then, we study cross diffusion systems which model congestion for several species. We are also interested in reaction-diffusion systems as diffusive prey-predator systems or tumor growth models. Finally, we introduce a new class of systems where the interaction is given by a multi-marginal transport problem. In many cases, we give numerical simulations to illustrate our theorical results.

Peripheral vascular grafts are used for the treatment of peripheral arterial disease and arteriovenous grafts for vascular access in end stage renal disease. The development of neo-intimal hyperplasia and thrombosis in the distal anastomosis remains the main reason for occlusion in that region. The local haemodynamics produced by a graft in the host vessel is believed to significantly affect endothelial function. Single spiral flow is a normal feature in medium and large sized vessels and it is induced by the anatomical structure and physiological function of the cardiovascular system. Grafts designed to generate a single spiral flow in the distal anastomosis have been introduced in clinical practice and are known as spiral grafts. In this work, spiral peripheral vascular and arteriovenous grafts were compared with conventional grafts using ultrasound and computational methods to identify their haemodynamic differences. Vascular-graft flow phantoms were developed to house the grafts in different surgical configurations. Mimicking components, with appropriate acoustic properties, were chosen to minimise ultrasound beam refraction and distortion. A dual-beam two-dimensional vector Doppler technique was developed to visualise and quantify vortical structures downstream of each graft outflow in the cross-flow direction. Vorticity mapping and measurements of circulation were acquired based on the vector Doppler data. The flow within the vascular-graft models was simulated with computed tomography based image-guided modelling for further understanding of secondary flow motions and comparison with the experimental results. The computational assessments provided a three-dimensional velocity field in the lumen of the models allowing a range of fluid dynamic parameters to be predicted. Single- or double-spiral flow patterns consisting of a dominant and a smaller vortex were detected in the outflow of the spiral grafts. A double- triple- or tetra-spiral flow pattern was found in the outflow of the conventional graft, depending on model configuration and Reynolds number. These multiple-spiral patterns were associated with increased flow stagnation, separation and instability, which are known to be detrimental for endothelial behaviour. Increased in-plane mixing and wall shear stress, which are considered atheroprotective in normal vessels, were found in the outflow of the spiral devices. The results from the experimental approach were in agreement with those from the computational approach. This study applied ultrasound and computational methods to vascular-graft phantoms in order to characterise the flow field induced by spiral and conventional peripheral vascular and arteriovenous grafts. The results suggest that spiral grafts are associated with advanced local haemodynamics that may protect endothelial function and thereby may prevent their outflow anastomosis from neo-intimal hyperplasia and thrombosis. Consequently this work supports the hypothesis that spiral grafts may decrease outflow stenosis and hence improve patency rates in patients.