INTRODUÇÃO: Baseados em estudo que evidenciou menor área de infarto do miocárdio (IM) em ratos submetidos a treinamento físico (TF),na ausência de reperfusão; e na liberação de endorfinas que ocorre durante o TF, nossos objetivos são: demonstrar se não só TF, mas também opióides e isquemia/reperfusão (IR) intermitente são capazes de reduzir área de IM, na ausência de reperfusão; se TF e opióides exibem efeito sinérgico e se o mecanismo de redução da área de IM pelo TF envolve receptores opióides. MATERIAIS E MÉTODOS: Ratos Wistar machos (n=76) foram divididos em 7 grupos:1- controle;2- TF (esteira elétrica,1 hora/dia,5 vezes/semana,por 12 semanas), antes do IM; 3- morfina antes do IM; 4- morfina+TF; 5- grupo com 3 ciclos de IR antes do IM; 6- naloxone antes da morfina; 7- naloxone antes de cada dia de TF. Todos os ratos foram submetidos à mensuração da pressão diastólica final (PDF) e a IM através da oclusão da artéria descendente anterior. A eficácia do TF foi avaliada através do consumo de oxigênio (VO2) e da distância máxima percorrida. Os ratos foram sacrificados no 8o pós-IM e a área de IM mensurada por planimetria. RESULTADOS: Não houve diferença no peso inicial (p=0,94), mortalidade (p=0,99), e relação peso cardíaco/peso corporal (p=0,29) entre os grupos. Entretanto, houve aumento do deltaVO2 (VO2 pico - VO2repouso) (p=0,0001)e da distância máxima percorrida (p=0,0001), nos grupos treinados. A PDF aumentou no pós-IM, em todos os grupos (p=0,0001). Os grupos tratados tiveram menor área de IM (p=0,0001), com exceção dos grupos morfina + naloxone e TF+ naloxone sendo que não houve maior redução no grupo TF+morfina. Os grupos TF e TF+morfina apresentaram maior espessura do septo inter-ventricular, em relação ao grupo controle (p=0,0008). Já o grupo TF + naloxone não apresentou maior espessura do septo IV, em relação aos outros grupos. Também não houve diferença na densidade capilar (p=0,88). CONCLUSÃO: Não só TF, mas também morfina e IR reduzem a área de IM, na ausência de reperfusão, sendo que não há efeito sinérgico entre TF e morfina. Esta redução não ocorre através do aumento da densidade capilar. Além disto, a ação do TF sobre a área de IM provavelmente ocorre através do estímulo de receptores opióides, visto que seu bloqueio anulou o efeito cardioprotetor do TF / BACKGROUND AND OBJECTIVES: Studies have shown a decrease in infarcted area in rats submitted to exercise training (ET), in the absence of reperfusion. Based on that, we tested four hypotheses: 1- not only ET but also another stimulus that causes myocardial protection, like opioid infusion and brief periods of ischemia-reperfusion (IR) before irreversible left anterior descending (LAD) coronary occlusion could reduce infarct area, 2- ET plus opioid infusion could have additive effects in reducing infarct size, 3- blocking the opioid system we could lose the myocardial protection caused by ET, 4-myocardial protection given by different strategies could occur due to the increase in capillary density. METHODS: Male Wistar rats (n=76) were randomly assigned to 7 groups: control (n=11); ET (n=12); morphine infusion before myocardial infarction (MI) (n=14); ET plus morphine (n=11); naloxone (a non selective opioid receptor blocker) plus morphin (n=9); intermittent IR (n=12) before MI; naloxone before each ET session (n=7). All groups were submitted to MI by LAD ligation technique and to measurement of left ventricular end-diastolic pressure (LVEDP) before and 5 min after MI. ET was performed on a treadmill for 60 min, 5 times/week for 12 weeks at 60% peak oxygen (peak VO2). To evaluate the efficacy of ET, we tested the exercise capacity and the peak VO2 before and after experimental period. Seven days after MI induction, rats were killed and hearts were harvested. Infarct size was expressed by evaluation of necrotic area, expressed as a % of the risk region (total left ventricle area). RESULTS: There were no differences in initial weight, cardiac/animal weight or mortality among groups. Exercise training increased exercise capacity (p=0.0001) and delta VO2 (VO2 peak-VO2 rest) (p=0.0001). Inter-ventricular septum thickness was higher in the ET and ET plus morphine groups, compared to the control group (p=0.0008). The LVEDP increased in the post-MI period, for all groups (p=0.0001). All treatment groups but not morphine plus naloxone and ET plus naloxone showed a decrease in infarcted area (p=0.0001). There was no additional decrease in infarct size in the ET+ morphine group, comparing with each group alone . There was no difference in capillary density for all groups. CONCLUSION: Not only ET, but also morphine and IR decrease infarcted area, in the absence of reperfusion. There is no additional effect between ET and morphine. Moreover, this reduction is not due to an increase in capillary density. The effect of ET in decreasing infarct size might occur by opioid receptor stimulus

Les ressources techniques, tactiques, physiques et mentales sont autant d’éléments à prendre en compte pour accéder à la performance en compétition. Pour autant, la spécificité du rugby à 7 attribue à la dimension physique une place particulière. La planification de l’entraînement, et en particulier la façon de gérer la charge à l’approche d’une compétition, devient ainsi une préoccupation permanente. Le but de cette thèse était d’étudier la réponse de joueurs internationaux de rugby à 7 à une gestion stratégique de la charge d’entraînement à l’approche d’une compétition. Notre première étude a consisté à décrire la distribution de la charge de travail sur une saison et caractériser différents modèles de périodisation. Ce travail a permis d’identifier l’affûtage comme une stratégie largement utilisée avant chaque tournée pour optimiser la performance physique des joueurs. Notre deuxième étude a consisté à montrer les effets d’une période d’affûtage sur les qualités physiques. L’observation des cinétiques de surcompensation des qualités de force, de vitesse et de répétition de sprints a démontré qu’une fenêtre comprise entre 9 et 16 jours constituait une durée optimale pour maximiser les gains. Enfin, notre dernière étude a porté sur une stratégie de pré-conditionnement mise en œuvre le jour de la compétition. Il s’agissait d’expérimenter les effets d’une séance d’entraînement, réalisée 2 heures avant le premier match du tournoi, sur les réponses physiques et psycho-physiologiques des joueurs. La capacité à répéter des sprints et l’activité physique en match n’ont pas été améliorées mais l’état psychophysiologique a été positivement influencé par cette séance. A travers cette thèse, nous avons donc essayé de dessiner une image générale d’une saison internationale de rugby à 7 et de questionner la pertinence de stratégies de périodisation mises en œuvre par les entraîneurs de l’équipe de France à l’approche des compétitions. Les conclusions scientifiques issues de ces études doivent être appréhendées comme des orientations qui guident les entraîneurs dans la construction de leurs scénarios d’entraînement. / The technical, tactical, physical and mental resources of a team are key factors to access to the performance in competition, and the Rugby-7’s specificity attributes a particular place to the physical dimension. Training periodization and in particular the way to manage training load prior to competition, is a permanent concern. The aim of this thesis was to study the response of international Rugby-7s players to strategic training load management in the pre-competition phases. Our first study examined the workload distribution over a season and identified different periodization models. This work helped identify the tapering phase as a strategy widely used before each competition to optimize players’ physical performance. The second study investigated the effects of a tapering period on physical qualities. The supercompensation kinetics of strength, speed and repetition of sprints qualities showed that a window between 9 and 16 days was an optimal duration to maximize physical performance. The final study focused on a preconditioning strategy implemented on the day of the competition. The aim was to examine the effects of a morning training session, completed 2 hours before the first match of the tournament, on the physical and psycho-physiological responses of the players. The repeated sprinting ability and physical activity in match was not improved, but the psychophysiological state was positively influenced by this session. Through this thesis, a general picture of a Rugby-7s international season was drawn and the relevance of periodization strategies implemented by the French team coaches in the approach of competitions was questioned. The scientific findings from these studies could be used as guidelines for coaches in building their training programs.

Cette thèse porte sur le problème de la diffration acoustique par un obstacle et sa résolution numérique par la méthode des éléments finis de frontière. Dans les trois premiers chapitres, on s'intéresse au cas où l'obstacle possède des singularités géométriques. Nous traitons le cas particulier des singularités de bord, courbes ouvertes en dimension 2, et surfaces ouvertes en dimension 3. Nous introduisons un formalisme qui permet de retrouver les bonnes propriétés de la méthode pour des objets réguliers. Une fonction de poids est définie sur les objets diffractant, et les opérateurs intégraux usuels (simple-couche et hypersingulier) sont renormalisés de manière adéquate par ce poids. Des préconditioneurs sont proposés sous la forme de racines carrées d'opérateurs locaux. En dimension 2, nous proposons une analyse théorique et numérique complète du problème. Nous montrons en particulier que les opérateurs intégraux renormalisés font partie d'une classe d'opérateurs pseudo-différentiels sur des courbes ouvertes, que nous introduisons et étudions ici. Le calcul pseudo-différentiel ainsi développé nous permet de calculer des paramétrices des les opérateurs intégraux qui correspondent aux versions continues de nos préconditionneurs. En dimension 3, nous montrons comment ces idées se généralisent théoriquement et numériquement dans le cas pour des surfaces ouvertes. Dans le dernier chapitre, nous introduisons une nouvelle méthode de calcul rapide des convolutions par des fonctions radiales en dimension 2, l'une des tâches les plus coûteuses en temps dans la méthode des éléments finis de frontière. Notre algorithme repose sur l'algorithme de transformée de Fourier rapide non uniforme, et est la généralisation un algorithme analogue disponible en dimension 3, la décomposition creuse en sinus cardinal. / In this thesis, we are concerned with the numerical resolution of the problem of acoustic waves scattering by an obstacle in dimensions 2 and 3, with the boundary element method. In the first three chapters, we consider objects with singular geometries. We focus on the case of objects with edge singularities, first open curves in the plane, and then open surfaces in dimension 3. We present a formalism that allows to restore the good properties that held for smooth objects. A weight function is defined on the scattering object, and the usual layer potentials (single-layer and hypersingular) are adequately rescaled by this weight function. Suitable preconditioners are proposed, that take the form of square roots of local operators. In dimension 2, we give a complete theoretical and numerical analysis of the problem. We show in particular that the weighted layer potentials belong to a class of pseudo-differential operators on open curves that we define and analyze here. The pseudo-differential calculus thus developed allows us to compute parametrices for the weighted layer potentials, which correspond to the continuous versions of our preconditioners. In dimension 3, we show how those ideas can be extended theoretically and numerically, for the particular case of the scattering by an infinitely thin disk. In the last chapter, we present a new method for the rapid evaluation of discrete convolutions by radial functions in dimension 2. Such convolutions represent a computational bottleneck in the boundary element methods. Our algorithm relies on the non-uniform fast Fourier transform and generalizes to dimension 2 an analogous algorithm available in dimension 3, namely the sparse cardinal sine decomposition.

Dans le domaine de l’électromagnétisme computationnel, les équations intégrales de frontière sont très largement utilisées pour résoudre certains des plus grands problèmes directs, grâce à leur grande efficacité. Cependant les équations intégrales du champ électrique et du champ combiné (EFIE et CFIE), deux des formulations les plus employées, souffrent d’instabilités à basse fréquence et à haute discrétisation, ce qui limite leur versatilité. Dans cette thèse différentes approches sont présentées pour obtenir des algorithmes applicables aussi bien à des problèmes de compatibilité électromagnétique qu’à des applications radar. Les solutions présentées incluent (i) l’extension des projecteurs dit quasi-Helmholtz (qH) aux modélisations d’ordre supérieur ; (ii) l’utilisation de ces projecteurs pour stabiliser l’équation intégrale du champ magnétique et former une CFIE extrêmement précise, augmentée par des techniques de type Calderón, qui ne souffre de problèmes ni à basse fréquence ni à haute discrétisation et qui n’est pas sujette aux résonances artificielles ; (iii) le développement d’une EFIE filaire, basée sur des B-splines linéaires et les projecteurs qH, stable aux deux extrémités du spectre. Ces travaux ont été suivis de l’ouverture d’un nouvel axe de recherche visant l’amélioration des techniques de résolution des problèmes inverses en électromagnétique, avec pour objectif principal l’augmentation des performances des interfaces cerveau machine (BCIs). Les premiers résultats obtenus incluent le développement de l’un des premiers systèmes libres de simulation de bout en bout de session de BCI ayant été publié après revue par les pairs. / In computational electromagnetics, boundary integral equations are the scheme of choice for solving extremely large forward electromagnetic problems due to their high efficiency. However, two of the most used of these formulations, the electric and combined field integral equations (EFIE and CFIE), suffer from stability issues at low frequency and dense discretization, limiting their applicability at both ends of the spectrum. This thesis focusses on remedying these issues to obtain full-wave solvers stable from low to high frequencies, capable of handling scenarios ranging from electromagnetic compatibility to radar applications. The solutions presented include (i) extending the quasi-Helmholtz (qH) projectors to higher order modeling thus combining stability with high order convergence rates; (ii) leveraging on the qH projectors to numerically stabilize the magnetic field integral equation and obtain a highly accurate and provably resonance-free Calderón-augmented CFIE immune to both of the aforementioned problems; and(iii) introducing a new low frequency and dense discretization stable wire EFIE based on projectors and linear B-splines. In addition, a research axis focused on enhancing Brain Computer Interface (BCIs) with high resolution electromagnetic modeling of the brain has been opened ; a particular attention is dedicated to the inverse problem of electromagnetics and the associated integral equation-based forward problem. The first results of this new line of investigations include the development of one of the first peer-reviewed, freely available framework for end-to-end simulation of BCI experiments.

Introduction In recent years, domain decomposition methods have been used extensively to efficiently solve boundary value problems for partial differential equations in complex{form domains. On the other hand, multilevel techniques on hierarchical data structures also have developed into an effective tool for the construction and analysis of fast solvers. But direct realization of multilevel techniques on a parallel computer system for the global problem in the original domain involves difficult communication problems. I this paper, we present and analyze a combination of these two approaches: domain decomposition and multilevel decomposition on hierarchical structures to design optimal preconditioning operators.

In this paper, we consider domain decomposition preconditioners for a system of linear algebraic equations arising from the <i>p</i>-version of the fem. We propose several multi-level preconditioners for the Dirichlet problems in the sub-domains in two and three dimensions. It is proved that the condition number of the preconditioned system is bounded by a constant independent of the polynomial degree. The proof uses interpretations of the <i>p</i>-version element stiffness matrix and mass matrix on [-1,1] as <i>h</i>-version stiffness matrix and weighted mass matrix. The analysis requires wavelet methods.

Anhydrobiotic organisms have the remarkable ability to lose extensive amounts of body water and survive in an ametabolic, suspended animation state. Distributed to various taxa of life, these organisms have evolved strategies to efficiently protect their cell membranes and proteins against extreme water loss. At the molecular level, a variety of mutually non-exclusive mechanisms have been proposed to account particularly for preserving the integrity of the cell membranes in the desiccated state. Recently, it has been shown that the dauer larva of the nematode Caenorhabditis elegans is anhydrobiotic and accumulates high amounts of trehalose during preparation for harsh desiccation (preconditioning), thereby allowing for a reversible desiccation / rehydration cycle. Here, we have used this genetic model to study the biophysical manifestations of anhydrobiosis and show that, in addition to trehalose accumulation, the dauer larvae exhibit a systemic chemical response upon preconditioning by dramatically reducing their phosphatidylcholine (PC) content. The C. elegans strain daf-2 was chosen for these studies, because it forms a constitutive dauer state under appropriate growth conditions. Using complementary approaches such as chemical analysis, time-resolved FTIR-spectroscopy, Langmuir-Blodgett monolayers, and fluorescence spectroscopy, it is shown that this chemical adaptation of the phospholipid (PL) composition has key consequences for their interaction with trehalose. Infrared-spectroscopic experiments were designed and automated to particularly address structural changes during fast hydration transients. Importantly, the coupling of headgroup hydration to acyl chain order at low humidity was found to be altered on the environmentally relevant time scale of seconds. PLs from preconditioned larvae with reduced PC content exhibit a higher trehalose affinity, a stronger hydration-induced gain in acyl chain free volume, and a wider spread of structural relaxation rates during lyotropic transitions and sub- headgroup H-bond interactions as compared to PLs from non-preconditioned larvae. The effects are related to the intrinsically different hydration properties of PC and phosphatidylethanolamine (PE) headgroups, and lead to a larger hydration-dependent rearrangement of trehalose-mediated H-bond network in PLs from preconditioned larvae. This results in a lipid compressibility modulus of ∼0.5 mN/m and 1.2 mN/m for PLs derived from preconditioned and non-preconditioned larvae, respectively. The ensemble of these changes evidences a genetically controlled chemical tuning of the native lipid composition of a true anhydrobiote to functionally interact with a ubiquitous protective disaccharide. The biological relevance of this adaptation is the preservation of plasma membrane integrity by relieving mechanical strain from desiccated trehalose- containing cells during fast rehydration. Finally, the thermo-tropic lipid phase behavior was studied by temperature-dependent ATR-FTIR and fluorescence spectroscopy of LAURDAN-labeled PLs. The results show that the adaptation to drought, which is accomplished to a significant part by the reduction of the PC content, relies on reducing thermo-tropic and enhancing lyotropic phase transitions. The data are interpreted on a molecular level emphasizing the influence of trehalose on the lipid phase transition under biologically relevant conditions by a detailed analysis of the lipid C=O H-bond environment. The salient feature of the deduced model is a dynamic interaction of trehalose at the PL headgroup region. It is proposed here that the location of trehalose is changed from a more peripheral to a more sub-headgroup-associated position. This appears to be particularly pronounced in PLs from preconditioned worms. The sugar slides deeper into the inter-headgroup space during hydration and thereby supports a quick lateral expansion such that membranes can more readily adapt to the volume changes in the swelling biological material at reduced humidity. The data show that the nature of the headgroup is crucial for its interaction with trehalose and there is no general mechanism by which the sugar affects lipidic phase transitions. The intercalation into a phosphatidylethanolamine-rich membrane appears to be unique. In this case, neither the phase transition temperature nor its width is affected by the protective sugar, whereas strong effects on these parameters were observed with other model lipids. With respect to membrane preservation, desiccation tolerance may be largely dependent on reducing phosphatidylcholine and increasing the phsophatidylethanolamine content in order to optimize trehalose headgroup interactions. As a consequence, fast mechanical adaptation of cell membranes to hydration-induced strain can be realized.

The Multiplicative Schwarz Preconditioned Inexact Newton (MSPIN) algorithm is presented as a complement to Additive Schwarz Preconditioned Inexact Newton (ASPIN). At an algebraic level, ASPIN and MSPIN are variants of the same strategy to improve the convergence of systems with unbalanced nonlinearities; however, they have natural complementarity in practice. MSPIN is naturally based on partitioning of degrees of freedom in a nonlinear PDE system by field type rather than by subdomain, where a modest factor of concurrency can be sacrificed for physically motivated convergence robustness. ASPIN, originally introduced for decompositions into subdomains, is natural for high concurrency and reduction of global synchronization. The ASPIN framework, as an option for the outermost solver, successfully handles strong nonlinearities in computational fluid dynamics, but is barely explored for the highly nonlinear models of complex multiphase flow with capillarity, heterogeneity, and complex geometry. In this dissertation, the fully implicit ASPIN method is demonstrated for a finite volume discretization based on incompressible two-phase reservoir simulators in the presence of capillary forces and gravity. Numerical experiments show that the number of global nonlinear iterations is not only scalable with respect to the number of processors, but also significantly reduced compared with the standard inexact Newton method with a backtracking technique. Moreover, the ASPIN method, in contrast with the IMPES method, saves overall execution time because of the savings in timestep size. We consider the additive and multiplicative types of inexact Newton algorithms in the field-split context, and we augment the classical convergence theory of ASPIN for the multiplicative case. Moreover, we provide the convergence analysis of the MSPIN algorithm. Under suitable assumptions, it is shown that MSPIN is locally convergent, and desired superlinear or even quadratic convergence can be obtained when the forcing terms are picked suitably. Numerical experiments show that MSPIN can be significantly more robust than Newton methods based on global linearizations, and that MSPIN can be more robust than ASPIN, and maintain fast convergence even for challenging problems, such as high-Reynolds number Navier-Stokes equations.

Numerical techniques for linear systems arising from discretization of partial differential equations are nowadays essential for understanding the physical world. Among these techniques, iterative methods and the accompanying preconditioning techniques have become increasingly popular due to their great potential on large scale computation. In this work, we present preconditioning techniques for linear systems built with tensor product basis functions. Efficient algorithms are designed for various problems by exploiting the Kronecker product structure in the matrices, inherited from tensor product basis functions. Specifically, we design preconditioners for mass matrices to remove the complexity from the basis functions used in isogeometric analysis, obtaining numerical performance independent of mesh size, polynomial order and continuity order; we also present a compound iteration preconditioner for stiffness matrices in two dimensions, obtaining fast convergence speed; lastly, for the Helmholtz problem, we present a strategy to `hide' its indefiniteness from Krylov subspace methods by eliminating the part of initial error that corresponds to those negative generalized eigenvalues. For all three cases, the Kronecker product structure in the matrices is exploited to achieve high computational efficiency.

Cell swelling may contribute to acute cell injury subsequent to ischemia/reperfusion. The potential role of mitochondrial uncoupling and the resultant mitochondrial swelling, due to opening of the mitochondrial permeability transition pore (MPTP), were examined in an in vitro ischemically pelleted isolated rabbit cardiomyocyte model using the protonophore, carbonyl cyanide m-chlorophenylhydrazone (CCCP) to uncouple mitochondria. Cyclosporin A (CsA) was employed to inhibit MPTP opening. Cell volume was determined by a cell-flotation, density-gradient assay, using bromododecane. Cell viability, subsequent to an osmotic stress, was determined by trypan blue permeability. Ischemic preconditioning (IPC) facilitated volume regulation following an osmotic stress. Ischemic-cell swelling was reduced by IPC. IPC protected ischemically pelleted cells, but CsA had no significant effects on injury or IPC protection. CCCP ischemia accelerated rates of ischemic contracture and injury, and abolished IPC protection. IPC protection was restored by CsA. In CCCP-ischemic-uncoupled cells, subjected to a reduced (170 mOsm) osmotic stress, CsA and IPC afforded independent and additive protection. Chelerythrine and 5-hydroxydecanoate (5-HD) blocked IPC, but did not reduce CsA protection. Electron microscopy confirmed that CCCP ischemia induced mitochondrial matrix swelling that was reduced by CsA. Cardioprotection by IPC and CsA was accompanied by proportional reductions in cell swelling. Morphometric analysis of the electron photomicrographs demonstrated that the mitochondrial volume fractions were significantly reduced in the CsA/CCCP (29.8 ± 2.3%, P < 0.004) and IPC/CsA/CCCP (31.5 ± 1.7%, P < 0.0008) groups as compared to the CCCP-ischemic group (40.5 ± 1.7%) The IPC/CCCP group (39.5 ± 4.2%) was not significantly different from the CCCP-ischemic group. NIM 811, a CsA analogue MPTP blocker with no calcineurin inhibitory activity, afforded protection similar to CsA. The results suggest that CsA protection may, in part, be mediated by reduction of mitochondrial swelling.