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

Introdução: O aumento da tolerância do miocárdio isquêmico observado durante o segundo de dois testes de esforços seqüenciais, o fenômeno do pré-aquecimento, foi proposto como um modelo clínico do pré-condicionamento isquêmico. Bloqueadores dos canais de K-ATP dependentes, tais como as sulfoniluréias, podem induzir a perda do pré-condicionamento isquêmico, o qual poderia estar envolvido no aumento dos eventos cardiovasculares. A repaglinida é um agente hipoglicemiante oral, pertencente à família da meglitinida e supostamente dotada de menor efeito no pré-condicionamento isquêmico, ainda que o fármaco tenha seu principal mecanismo de ação nos canais de K-ATP dependentes. Objetivos e Métodos: O objetivo foi investigar os efeitos da repaglinida no fenômeno do pré-condicionamento isquêmico em pacientes diabéticos com doença coronariana estável. Foram estudados 42 pacientes diabéticos tipo 2, com angina estável e doença arterial documentada. Todos os pacientes tinham testes ergométricos positivos para isquemia. Na primeira fase do teste, a sulfoniluréia e os betabloqueadores foram suspensos por trinta dias e sete dias, respectivamente. Os pacientes foram submetidos a dois testes ergométricos seqüenciais, com intervalo de trinta minutos (testes 1 e 2). Na segunda fase, os pacientes receberam repaglinida por sete dias e mais dois testes ergométricos foram repetidos (testes 3 e 4). Resultados: Todos os pacientes alcançaram ST >1 mm na primeira fase (Teste 1 e 2). O tempo alcançado no teste 2 foi maior que aquele alcançado no teste 1 (4:44s. x 5:37s. p=0,001), como também foi maior a duração do exercício (6:15s x 6:29s. p=0,008), denotando pré-condicionamento isquêmico. Após o uso da repaglinida, nos testes 3 e 4, observou-se menor tempo alcançado para atingir isquemia no teste 4 (5:37s. x 4:58s. p=0,001). Observou-se, ainda, menor tempo de tolerância ao exercício na fase 2 (6:57s x 6:34s. p=0,007). Em relação ao surgimento de angina, não se constataram diferenças estatísticas entre as duas fases. Conclusão: Nos pacientes diabéticos com doença coronariana estável, a repaglinida bloqueou o pré-condicionamento isquêmico. / Background: The increase of tolerance to myocardial ischemia observed during the second of two sequential exercise tests, the warm-up phenomenon, has been proposed as a clinical model of ischemic preconditioning. Blockers of K-ATP channels, such as the Sulfonylurea drugs, can induce loss of ischemic preconditioning, what could be involved in an increase of cardiac events. Repaglinide is a hypoglycemic agent with supposedly lower influence on ischemic preconditioning, despite acting in K-ATP channels. Objectives and Methods: This study investigated the effects of repaglinide on the ischemic preconditioning in diabetic patients with CAD. There were 42 patients and inclusion criteria were positive treadmill test for myocardial ischemia. Sulphonylureas and beta-blocking agents were withdrawn 30 and 7 days respectively before phase 1 of the study. In this phase, the patients underwent two consecutive treadmill exercise tests at 30 minute intervals (test 1 and test 2). In phase 2 of the study, all patients received repaglinide 2 mg three times daily during 7 days before treadmill exercise test (test 3 and test 4). Results: All patients achieved 1.0 mm ST-segment depression during phase 1. The time achieved to ST depression during test 2 was greater than that during test 1 (4:44s vs. 5:37s. p=0.001) as well as the duration of the exercise (6:15s vs.6: 29s. p=0.008), suggesting a higher ischemic threshold. In phase 2 after repaglinide, all patients achieved 1 mm ST-segment depression. However, the time achieved to ST depression, as well as the duration of the exercise, was lower in test 4 comparing with test 3. There were no statistical differences regarding angina episodes in phase 1 or phase 2. Conclusions: In diabetic patients with stable coronary disease, the oral hypoglycemic agent repaglinide abolished the myocardial ischemic preconditioning.

L'équation intégrale du champ électrique (EFIE) et l'équation intégrale du champ combiné (CFIE) souffrent d'un mauvais conditionnement à haute discrétisation et à bassefréquence : si la taille moyenne des arrêtes du maillage est réduite ou si la fréquence est diminuée le conditionnement du système se dégrade rapidement. Cela provoque le ralentissement ou la non convergence des solveurs itératifs. Cette dissertation présente de nouveaux paradigmes permettant l'obtention de solveurs à convergence rapide pour équations intégrales; pour prévenir la dégradation du conditionnement nous avançons l'état de l'art des techniques de préconditionnement dites de Calderon et de celles reposant sur l'utilisation des bases hiérarchiques. Pour traiter l'EFIE, nous introduisons une base hiérarchique pour maillages structurés et non-structurés dérivant des pré-ondelettes primaires et duales de Haar. De plus, nous introduisons un nouveau cadre permettant de préconditionner efficacement l'EFIE dans le cas d'objets à connexion multiples. L'applicabilité à la CFIE des préconditionneurs à bases hiérarchiques fait l'objet d'une étude aboutissant à la formalisation d'une technique de préconditionnement. Nous présentons aussi un préconditionneur multiplicatif de type Calderon (RF-CMP) qui permet l'obtention d'une matrice système Hermitienne, définie positive (HDP) et bien conditionnée, sans avoir recours, contrairement aux préconditionneurs existants, au raffinement du maillage ni à l'utilisation de fonction duales. Puisque la matrice est HPD, la méthode du gradient conjugué peut servir de solveur itératif avec une convergence garantie. / The electric field integral equation (EFIE) and the combined field integral equation(CFIE) suffer from the dense-discretization and the low-frequency breakdown: if the average edgelength of the mesh is reduced, or if the frequency is decreased, then the condition number of the system matrix grows. This leads to slowly or non-converging iterative solvers. This dissertation presents new paradigms for rapidly converging integral equation solvers: to overcome the illconditioning, we advance and extend the state of the art both in hierarchical basis and in Calderón preconditioning techniques. For the EFIE, we introduce a hierarchical basis for structured and unstructured meshes based on generalized primal and dual Haar prewavelets. Furthermore, a framework is introduced which renders the hierarchical basis able to efficiently precondition the EFIE in the case that the scatterer is multiply connected. The applicability of hierarchical basis preconditioners to the CFIE is analyzed and an efficient preconditioning scheme is derived. In addition, we present a refinement-free Calderón multiplicative preconditioner (RF-CMP) that yields a system matrix which is Hermitian, positive definite (HPD), and well-conditioned. Different from existing Calderón preconditioners, no dual basis functions and thus no refinement of the mesh is required. Since the matrix is HPD—in contrast to standard discretizations of the EFIE—we can apply the conjugate gradient (CG) method as iterative solver, which guarantees convergence. Eventually, the RF-CMP is extended to the CFIE.

Very fine discretizations of differential operators often lead to large, sparse matrices A, where the condition number of A is large. Such ill-conditioning has well known effects on both solving linear systems and eigenvalue computations, and, in general, computing solutions with relative accuracy independent of the condition number is highly desirable. This dissertation is divided into two parts. In the first part, we discuss a method of preconditioning, developed by Ye, which allows solutions of Ax=b to be computed accurately. This, in turn, allows for accurate eigenvalue computations. We then use this method to develop discretizations that yield accurate computations of the smallest eigenvalue of the biharmonic operator across several domains. Numerical results from the various schemes are provided to demonstrate the performance of the methods. In the second part we address the role of the condition number of A in the context of multigrid algorithms. Under various assumptions, we use rigorous Fourier analysis on 2- and 3-grid iteration operators to analyze round off errors in floating point arithmetic. For better understanding of general results, we provide detailed bounds for a particular algorithm applied to the 1-dimensional Poisson equation. Numerical results are provided and compared with those obtained by the schemes discussed in part 1.

We study the preconditioning of symmetric indefinite linear systems of equations that arise in interior point solution of linear optimization problems. The preconditioning method that we study exploits the block structure of the augmented matrix to design a similar block structure preconditioner to improve the spectral properties of the resulting preconditioned matrix so as to improve the convergence rate of the iterative solution of the system. We also propose a two-phase algorithm that takes advantage of the spectral properties of the transformed matrix to solve for the Newton directions in the interior-point method. Numerical experiments have been performed on some LP test problems in the NETLIB suite to demonstrate the potential of the preconditioning method discussed. / Singapore-MIT Alliance (SMA)

The solution of large and sparse eigenvalue problems arising from the discretization of the diffusion equation is considered. The multigroup diffusion equation is discretized by means of the Nodal expansion Method (NEM) [9, 10]. A new formulation of the higher order NEM variants revealing the true nature of the problem, that is, a generalized eigenvalue problem, is proposed. These generalized eigenvalue problems are solved using the Jacobi-Davidson (JD) method [26]. The most expensive part of the method consists of solving a linear system referred to as correction equation. It is solved using Krylov subspace methods in combination with aggregation-based Algebraic Multigrid (AMG) techniques. In that context, a particular aggregation technique used in combination with classical smoothers, referred to as oblique geometric coarsening, has been derived. Its particularity is that it aggregates unknowns that are not coupled, which has never been done to our knowledge. A modular code, combining JD with an AMG preconditioner, has been developed. The code comes with many options, that have been tested. In particular, the instability of the Rayleigh-Ritz [33] acceleration procedure in the non-symmetric case has been underlined. Our code has also been compared to an industrial code extracted from ARTEMIS.

The present study aims to develop a mechanistic understanding of the thermal-hydraulic processes in a vapor explosion, which may occur in nuclear power plants during a hypothetical severe accident involving interactions of high-temperature corium melt and volatile coolant. Over the past several decades, a large body of literature has been accumulated on vapor explosion phenomenology and methods for assessment of the related risk. Vapor explosion is driven by a rapid fragmentation of high temperaturemelt droplets, leading to a substantial increase of heattransfer areas and subsequent explosive evaporation of the volatile coolant. Constrained by the liquid-phase coolant, the rapid vapor production in the interaction zone causes pressurization and dynamic loading on surrounding structures. While such a general understanding has been established, the triggering mechanism and subsequent dynamic fine fragmentation have yet not been clearly understood. A few mechanistic fragmentation models have been proposed, however, computational efforts to simulate the phenomena generated a large scatter of results. Dynamics of the hot liquid (melt) droplet and the volatile liquid (coolant) are investigated in the MISTEE (Micro-Interactions in Steam Explosion Experiments) facility by performing well-controlled, externally triggered, single-droplet experiments, using a high-speed visualization system with synchronized digital cinematography and continuous X-ray radiography, called SHARP (Simultaneous High-speed Acquisition of X-ray Radiography and Photography). After an elaborate image processing, the SHARP images depict the evolution of both melt material (dispersal) and coolant (bubble dynamics), and their microscale interactions, i.e. the triggering phenomenology. The images point to coolant entrainment into the droplet surface as the mechanism for direct contact/mixing ultimately responsible for energetic interactions. Most importantly, the MISTEE data reveals an inverse correlation between the coolant temperature and the molten droplet deformation/prefragmentation during the first bubble dynamics cycle. The SHARP observations followed by further analysis leads to a hypothesis about a novel phenomenon called pre-conditioning, according to which dynamics of the first bubble-dynamics cycle and the ability of the melt drop to deform/pre-fragment dictate the subsequent explosivity of the so-triggered droplet. The effect of non-condensable gases on the perceived mechanisms was investigated on the MISTEE-NCG test campaign, in which a considerable amount of non-condensable gases (NCG) are present in the film that enfolds the molten droplet. The SHARP images for the MISTEE-NCG tests were analyzed and special attention was given to the morphology (aspect ratio) and dynamics of the air/ vapor bubble, as well as the melt drop preconditioning and interaction energetics. Analysis showed twomain aspects when compared to the MISTEE test series (withoutentrapped air). First, the investigation showed that the meltpreconditioning still strongly depends on the coolant subcooling. Second,in respect to the energetics, the tests consistently showed a reducedconversion ratio compared to that of the MISTEE test series. The effect of the melt material in the steam explosion triggerability was also summoned, since it would in principle directly implicate the melt preconditioning. Since a number of the thermo-physical properties of the material would influence the triggering process, we focused on the material properties by using the same dioxide material with difference concentrations, i.e. eutectic and non-eutectic. Unfortunately, due to the high melt superheat the possible differences were not perceived. Thus, inaddition to other materials, lower melt superheat tests were schedule inthe future. / QC 20101110

As a result of predicted climate change, environmental conditions may make woody plant species such as poplars (Populus spp.) vulnerable unless they are sufficiently adaptable to the new environment. This greenhouse study examined the responses of Hill, Northwest, Okanese and Walker hybrid poplar clones to drought, a potential outcome of a changing climate. Plants were grown from cuttings and subjected to two soil moisture treatments; a well-watered treatment and a drought conditioning treatment in which plants were subjected to cycles of soil moisture deficit. The first study examined growth and gas exchange following treatments, while the second study examined concurrent changes in leaf water potential and gas exchange during a period of increasing soil moisture deficit, following treatments.<p> Hill and Okanese plants had reduced shoot:root ratios, possibly leading to more positive plant moisture balances compared to Northwest and Walker plants. Stomatal characteristics related to steady state gas exchange with Okanese plants having stomata predominantly on lower leaf surfaces, and lower stomatal conductance and Northwest plants having relatively large stomata and increased stomatal conductance. Hill and Okanese plants had the most responsive stomata, which began to close at much higher levels of leaf water potential (-0.45 and -0.54 MPa) than Northwest or Walker plants (-1.03 and -0.88 MPa); however, closure was more gradual in Okanese plants. Drought preconditioning resulted in stomatal closure occurring at higher leaf water potentials in droughted Northwest and Walker plants compared to well-watered plants. Regardless of soil moisture treatment, WUE was highest in Okanese and Walker plants. The drought treatment did however lead to increased WUE in Hill and Northwest plants.<p> Overall, Okanese plants appear to be the best adapted to conditions of reduced soil moisture based on growth and physiological traits, while Northwest and Hill seem better suited to areas where moisture deficits are likely to be less frequent or less severe. Results indicate that variability exists in adaptability of hybrid poplar clones to drought, suggesting that there may also be other hybrid clones that are adaptable to reduced soil moisture conditions, which may merit further investigation.

As a result of predicted climate change, environmental conditions may make woody plant species such as poplars (Populus spp.) vulnerable unless they are sufficiently adaptable to the new environment. This greenhouse study examined the responses of Hill, Northwest, Okanese and Walker hybrid poplar clones to drought, a potential outcome of a changing climate. Plants were grown from cuttings and subjected to two soil moisture treatments; a well-watered treatment and a drought conditioning treatment in which plants were subjected to cycles of soil moisture deficit. The first study examined growth and gas exchange following treatments, while the second study examined concurrent changes in leaf water potential and gas exchange during a period of increasing soil moisture deficit, following treatments.<p> Hill and Okanese plants had reduced shoot:root ratios, possibly leading to more positive plant moisture balances compared to Northwest and Walker plants. Stomatal characteristics related to steady state gas exchange with Okanese plants having stomata predominantly on lower leaf surfaces, and lower stomatal conductance and Northwest plants having relatively large stomata and increased stomatal conductance. Hill and Okanese plants had the most responsive stomata, which began to close at much higher levels of leaf water potential (-0.45 and -0.54 MPa) than Northwest or Walker plants (-1.03 and -0.88 MPa); however, closure was more gradual in Okanese plants. Drought preconditioning resulted in stomatal closure occurring at higher leaf water potentials in droughted Northwest and Walker plants compared to well-watered plants. Regardless of soil moisture treatment, WUE was highest in Okanese and Walker plants. The drought treatment did however lead to increased WUE in Hill and Northwest plants.<p> Overall, Okanese plants appear to be the best adapted to conditions of reduced soil moisture based on growth and physiological traits, while Northwest and Hill seem better suited to areas where moisture deficits are likely to be less frequent or less severe. Results indicate that variability exists in adaptability of hybrid poplar clones to drought, suggesting that there may also be other hybrid clones that are adaptable to reduced soil moisture conditions, which may merit further investigation.

In this paper matrix compression techniques in the context of wavelet Galerkin schemes for boundary integral equations are developed and analyzed that exhibit optimal complexity in the following sense. The fully discrete scheme produces approximate solutions within discretization error accuracy offered by the underlying Galerkin method at a computational expense that is proven to stay proportional to the number of unknowns. Key issues are the second compression, that reduces the near field complexity significantly, and an additional a-posteriori compression. The latter one is based on a general result concerning an optimal work balance, that applies, in particular, to the quadrature used to compute the compressed stiffness matrix with sufficient accuracy in linear time. The theoretical results are illustrated by a 3D example on a nontrivial domain.