Les interactions entre les flammes et les phénomènes thermiques sont le fil conducteur de ce travail. En effet, les flammes produisent de la chaleur, mais peuvent aussi être affectées par des transferts ou des sources de chaleur. La Simulation aux Grandes Echelles (SGE) est utilisée ici pour étudier ces interactions, en mettant l’accent sur deux sujets principaux: le transfert de chaleur aux parois et le contrôle de la combustion. Dans un premier temps, on étudie le transfert de chaleur aux parois dans un modèle de brûleur CH4/O2 de moteur-fusée. Dans un contexte deréutilisabilité et de réduction des coûts des lanceurs, qui constituent des enjeux majeurs, de nouveaux couples de propergols sont envisagés et les flux thermiques à la paroi doivent êtreprécisément prédits. Le but de ce travail est d’évaluer les besoins et les performances des SGEpour simuler ce type de configuration et de proposer une méthodologie de calcul permettant desimuler différentes configurations. Les résultats numériques sont comparés aux donnéesexpérimentales fournies par la Technische Universität München (Allemagne). Dans un deuxième temps, le contrôle de la combustion au moyen de décharges de plasma de type NRP (en anglaisNanosecond Repetitively Pulsed) est étudié. Les systèmes de turbines à gaz modernes utilisent en effet une combustion pauvre dans le but de réduire la consommation de carburant et les émissions de polluants. Les flammes pauvres sont connues pour être sujettes à des instabilités et le contrôle de la combustion peut jouer un rôle majeur dans ce domaine. Un modèle phénoménologique qui considère les décharges de plasma comme une source de chaleur est développé et appliqué à un brûleur pauvre avec prémélange CH4/Air stabilisé par un swirler. LesSGE sont réalisées afin d’évaluer les effets des décharges NRP sur la flamme. Les résultats numériques sont comparés aux observations expérimentales faites à la King Abdulla University ofScience and Technology (Arabie Saoudite) / Interactions between flames and thermal phenomena are the guiding thread of this work. Flamesproduce heat indeed, but can also be affected by it. Large Eddy Simulations (LES) are used hereto investigate these interactions, with a focus on two main topics: wall heat transfer andcombustion control. In a first part, wall heat transfer in a rocket engine sub-scale CH4/O2 burner isstudied. In the context of launchers re-usability and cost reduction, which are major challenges,new propellant combinations are considered and wall heat fluxes have to be precisely predicted.The aim of this work is to evaluate LES needs and performances to simulate this kind ofconfiguration and provide a computational methodology permitting to simulate variousconfigurations. Numerical results are compared to experimental data provided by the TechnischeUniversität München (Germany). In a second part, combustion control by means of NanosecondRepetitively Pulsed (NRP) plasma discharges is studied. Modern gas turbine systems use indeedlean combustion with the aim of reducing fuel consumption and pollutant emissions. Lean flamesare however known to be prone to instabilities and combustion control can play a major role in thisdomain. A phenomenological model which considers the plasma discharges as a heat source isdeveloped and applied to a swirl-stabilized CH4/Air premixed lean burner. LES are performed inorder to evaluate the effects of the NRP discharges on the flame. Numerical results are comparedwith experimental observations made at the King Abdulla University of Science and Technology(Saudi Arabia).

Cette thèse a pour objet la simulation d'une zone de mélange turbulente issue de l'instabilité de Richtmyer-Meshkov à l'aide d'un modèle à fonction de densité de probabilité (PDF). Nous analysons plus particulièrement la prise en charge par le modèle PDF du transport de l'énergie cinétique turbulente dans la zone de mélange.Dans cette optique, nous commençons par mettre en avant le lien existant entre les statistiques en un point de l'écoulement et ses conditions initiales aux grandes échelles. Ce lien s'exprime à travers le principe de permanence des grandes échelles, et permet d'établir des prédictions pour certaines grandeurs de la zone de mélange, telles que son taux de croissance ou son anisotropie.Nous dérivons ensuite un modèle PDF de Langevin capable de restituer cette dépendance aux conditions initiales. Ce modèle est ensuite validé en le comparant à des résultats issus de simulations aux grandes échelles (LES).Enfin, une analyse asymptotique du modèle proposé permet d'éclairer notre compréhension du transport turbulent. Un régime de diffusion est mis en évidence, et l'expression du coefficient de diffusion associé à ce régime atteste l'influence de la permanence des grandes échelles sur le transport turbulent.Tout au long de cette thèse, nous nous sommes appuyés sur des résultats issus de simulations de Monte Carlo du modèle de Langevin. A cet effet, nous avons développé une méthode spécifique eulérienne et à l'avons comparé à des alternatives lagrangiennes. / The aim of the thesis is to simulate a turbulent mixing zone resulting from the Richtmyer-Meshkov instability using a probability density function (PDF) model. An emphasis is put on the analysis of the turbulent kinetic energy transport.To this end, we first highlight the link existing between the one-point statistics of the flow and its initial conditions at large scales. This link is expressed through the principle of permanence of large eddies, and allows to establish predictions for quantities of the mixing zone, such as its growth rate or its anisotropy.We then derive a Langevin PDF model which is able to reproduce this dependency of the statistics on the initial conditions. This model is then validated by comparing it against large eddy simulations (LES).Finally, an asymptotic analysis of the derived model helps to improve our understanding of the turbulent transport. A diffusion regime is identified, and the expression of the diffusion coefficient associated with this regime confirms the influence of the permanence of large eddies on the turbulent transport.Throughout this thesis, our numerical results were based on Monte Carlo simulations for the Langevin model. In this regard, we proceeded to the development of a specific Eulerian method and its comparison with Lagrangian counterparts.

L'objectif de la présente étude est d'analyser la modélisation de la turbulence de simulations en moyenne de Reynolds (RANS) dans le cadre d'écoulements de type turbomachines, en utilisant des simulations aux grandes échelles (SGE) comme référence. L'étude porte sur deux cas test: un décollement de coin dans une grille d'aubes rectiligne, et un écoulement de jeu pour un aubage isolé dans un jet. Deux lois de comportement, la loi de comportement de Boussinesq et la loi de comportement quadratique (quadratic constitutive relation ou QCR), sont analysées, avec deux versions du modèle de turbulence k-omega de Wilcox. Les lois de comportement étudiées reposent sur deux hypothèses: une hypothèse d'alignement entre le tenseur de Reynolds et un tenseur construit à partir de l'écoulement moyen, et une hypothèse sur la viscosité turbulente. L'hypothèse d'alignement est étudiée à partir de la SGE, pour laquelle les deux tenseurs sont indépendamment connus, en utilisant un indicateur construit sur le produit scalaire des tenseurs. Les résultats sont présentés sous forme d'une fonction de répartition de la valeur de l'indicateur pour le domaine complet, puis pour trois sous-domaines d'intérêt: l'entrée, une région où l'écoulement interagit fortement avec les parois, et une région où l'écoulement est fortement tourbillonnaire. L'hypothèse d'alignement n'est que rarement valide pour la loi de comportement de Boussinesq. Pour la QCR, les résultats sont meilleurs en entrée, comparé à la loi de Boussinesq. Il ne sont cependant pas meilleurs pour les régions où l'écoulement est plus tourbillonnaire. Une amélioration de la loi de comportement est nécessaire pour pouvoir faire progresser la modélisation turbulente en RANS. En revanche, l'utilisation de l'énergie cinétique turbulente et du taux de dissipation spécifique semble correcte pour estimer la valeur de la viscosité turbulente. L'analyse de la modélisation de l'équation d'énergie cinétique turbulente (ECT) est réalisée au travers d'une comparaison terme à terme avec l'équation d'ECT résolue par la SGE. Les résultats SGE présentent une turbulence qui n'est pas à l'équilibre : la production et la dissipation ne sont pas superposées, et le terme de transport est important. Pour le RANS, la turbulence est à l'équilibre : la production et la dissipation sont superposées, et le terme de transport est de faible intensité. Un modèle de turbulence qui prend en compte le déséquilibre est nécessaire pour améliorer ce point. En dernier lieu, une nouvelle formulation hybride RANS/SGE est proposée, fondée sur la distance à la paroi en unités de paroi. La formulation est validée dans un canal bi-périodique et un premier essai est réalisé sur le cas de décollement de coin, mais d'autres analyses sont nécessaires avant que cette formulation ne soit fonctionnelle. / The present study aims at analysing turbulence modelling in Reynolds-averaged Navier-Stokes (RANS) simulations, in the context of turbomachinery flows, using large-eddy simulations (LES) as references. Two test cases are considered: a corner separation (CS) flow in a linear compressor cascade, and a tip-leakage (TL) flow of a single blade in a jet. Two constitutive relations, the Boussinesq constitutive relation and the quadratic constitutive relation (QCR), are investigated, with two versions of Wilcox's $k-\omega$ turbulence model. The studied constitutive relations rely on two hypotheses: an alignment hypothesis between the Reynolds stress tensor and a mean flow tensor, and an hypothesis on the turbulent viscosity. The alignment hypothesis is investigated using LES, where both the tensors are known independently, with an indicator built on the inner product of the tensors. The results are presented as probability density functions of the indicator value for the entire domain first, and then for three specific areas of interest: the inlet area, similar to a boundary-layer flow, an area of strong interaction between the flow and the walls (CS: passage area, TL: tip clearance) and an area of highly vortical flow (CS: separation wake, TL: tip-leakage vortex). The alignment hypothesis is rarely verified in any area for the Boussinesq constitutive relation. For the QCR, the results are improved for the inlet areas compared to the Boussinesq constitutive relation, but no significant improvement is found in the highly vortical regions. An improvement of the constitutive relation is needed in order to improve the RANS turbulence modelling. In contrast, the use of the turbulent kinetic energy and the specific dissipation rate appears quite correct to estimate the turbulent viscosity. The modelling of the RANS turbulent kinetic energy (TKE) budget equation is investigated through a term to term comparison with the resolved LES TKE budget equation. The LES presents a turbulence that is not at equilibrium, with the production and the dissipation not superimposed, and an important amount of transport. This differs from the RANS models, at equilibrium: the production and the dissipation are superimposed, with a small amount of transport. The development of a non-equilibrium turbulence model for RANS simulations could improve this aspect of turbulence modelling. Finally, a new hybrid RANS-LES formulation, based on the wall distance in wall units, is also proposed. It is validated on a bi-periodical channel flow, and a first attempt is made on the corner separation case, but further investigations are still needed for the model to be fully operational.

[pt] Pontes com vãos superiores a 2.000 m tornam-se muito sensíveis à ação do vento, particularmente ao drapejamento. Nesta tese é estudado um método para a supressão do drapejamento em pontes de grandes vãos através de um controle aerodinâmico ativo. Apresentam-se técnicas analíticas de projeto para o controle ativo do sistema aero elástico constituído pelo tabuleiro e por duas superfícies de controle. Estas técnicas são baseadas em aproximações racionais das cargas aerodinâmicas não permanentes (ou auto-excitadas) no domínio Laplaciano, no qual as equações de movimento são representadas por equações matriciais de coeficientes constantes. A primeira parte da tese é dedicada à formulação matricial das funções racionais conhecida como Minimum State, assim como a aplicações a dados aerodinâmicos obtidos experimentalmente para vários tipos de seções transversais de pontes. A precisão das aproximações é calculada. Desenhos dos derivativos aerodinâmicos, dados sob forma de tabelas, e das respectivas aproximações, são elaborados para fins de comparação. Em seguida, são apresentadas as equações em espaço de estado descrevendo o comportamento aeroelástico de uma seção transversal de ponte. A partir dos dados geométricos e características dinâmicas de uma determinada ponte, (massa, momento de inertia polar, frequências naturais e fatores de amortecimento), e assumindo a semelhança geométrica entre as seções transversais da ponte em verdadeira grandeza e do modelo em escala do qual os derivativos aerodinâmicos foram extraídos, é possível calcular a velocidade crítica desta ponte, utilizando os programas em linguagem MATLAB apresentados no corpo deste trabalho. Esta parte da tese mostra ser possível construir um catálogo com vários perfis de pontes, caracterizados por derivativos aerodinâmicos variáveis em função de frequências reduzidas adimensionais, e das funções racionais correspondentes. A segunda parte é dedicada à fomulação das equações de movimento em espaço de estado, descrevendo o comportamento aeroelástico do sistema tabuleiro - superfícies de controle. As equações resultantes são ampliadas com novos estados aerodinâmicos responsáveis pela modelagem da influência do fluxo de ar sobre o tabuleiro e sobre as superfícies de controle em movimento. As equações de movimento são função da velocidade média do vento incidente. A dependência da equação de movimento à velocidade do vento motivou a aplicação dos conceitos de realimentação de ganhos, constante e variável, ao problema da supressão do drapejamento, os quais são apresentados separadamente em dois capítulos.O enfoque de ganho variável de saída é formulado em termos de minimização de um índice de desempenho dimensionalmente proporcional à soma do trabalho realizado pelas superfícies de controle e da energia cinética proporcional à velocidade vertical do tabuleiro. Apresenta-se também em detalhe um método sistemático para determinar a matriz de controle de ganhos variável, aplicada ao caso hipotético da ponte de Gibraltar. Neste caso, o conceito de realimentação de ganhos variável mostrou-se muito efetivo em suprimir o drapejamento do tabuleiro da ponte. Diferentes características geométricas e dinâmicas de outras pontes podem ser introduzidas nos programas MATLAB apresentados no Apêndice, para obtenção da velocidade crítica nos casos de tabuleiros isolados, tabuleiros com asas estacionárias e tabuleiros com asas giratórias ativamente controladas, para supressão do drapejamento do tabuleiro. / [en] Long span bridges, with main spans beyond 2.000 m become highly sensitive to wind action, particularly to flutter. An active aerodynamic control method of suppressing flutter of very long span bridges is studied in this thesis. Analytical design techniques for active control of the aeroelastic system consisting of the bridge deck and two control surfaces are presented. These techniques are based on a rational approximation of the unsteady aerodynamic loads in the entire Laplace domain, which yieds matrix equations of motion with constant coefficientes. The first part of this thesis is dedicated to the matrix formulation of the rational functions known as Minimum State and to applications to aerodynamic data obtained experimentally for various types of bridge profiles. The precision of the approximations iscalculated, and plots of the approximation functions compared to the available tabular data are drawn. Next, the state-space equations of motion describing the aeroelastic behaviour of a section of a bridge deck is presented. Given the dynamic data of a bridge structure (mass, rotational mass moment of inertia, natural frequencies, stiffness and damping ratios), and assuming that a geometric similitude exists between the profiles of the full-scale bridge deck and the sectional model from which the frequency dependent aerodynamic data was extracted, it is possible to calculate the critical velocity of that particular bridge. This part of the thesis shows that it is possible to build up a catalog of several profiles, characterized by frequency dependent aerodynamic data and the corresponding rational functions. The second part is dedicated to the formulation of the state-space equations of motion describing the aeroelastic behaviour of the entire system consisting of the bridge deck and control surfaces. The resulting equation includes new aerodynamic states which model the air flow influence on the moving deck. The equation of motion is a function of the mean velocity of the incoming wind. The dependence of the equation of motion on the wind velocity motivated the application of a constant and a variable-gain feedback concept to the problem of flutter suppressing, which are presented separatelly. The output variable-gain approach is formulated in terms of minimizing a performance index dimensionally proportional to the sum of the work done by the rotating control surfaces and the kinetic energy of the heaving velocity. A sistematic method to determine the matrix of variable control gains is shown in detail, as applied to the hypothethical case of Gibraltar bridge. Application of the variablegain feedback concept was found to be very effective in suppressing flutter of the bridge deck. Different geometric and dynamic characteristics can be introduced in the MATLAB programs included in this work, in order to obtain the critical velocities of a bridge deck alone, a bridge deck with stationary wings and a bridge with moving wings activelly controled.

Introdução: A correção anatômica da transposição das grandes artérias após o período neonatal demanda a preparação prévia do ventrículo subpulmonar, com bandagem do tronco pulmonar, para induzir a hipertrofia ventricular. Estudos experimentais prévios demonstraram que a sobrecarga sistólica intermitente determina uma hipertrofia ventricular mais eficiente, em relação à bandagem convencional (fixa) do tronco pulmonar. Os mecanismos adaptativos envolvidos no retreinamento do ventrículo subpulmonar ainda não estão completamente estabelecidos, pois se sabe que, além da hipertrofia e hiperplasia das células contráteis, também células do interstício e vasos sofrem alterações fenotípicas. Permanece indefinida a taxa ideal de incremento, tanto da matriz extracelular quanto da vascularização do miocárdio na situação do retreinamento ventricular, para suportar a resistência sistêmica. Objetivo: Avaliar a adaptação do ventrículo subpulmonar no que se refere a apoptose e estímulo à neovascularização miocárdica em resposta à sobrecarga pressórica contínua versus intermitente, obtida pela bandagem ajustável do tronco pulmonar de cabritos jovens. Método: Foram utilizados 21 cabritos hígidos, com idade de 30 a 60 dias e pesos comparáveis, divididos em três grupos: Controle (n = 7, sem sobrecarga sistólica), Contínuo (n = 7, sobrecarga sistólica contínua do VD), Intermitente (n = 7, 12 horas/dia de sobrecarga sistólica intermitente do VD). A sobrecarga sistólica do VD foi mantida por 96 horas no grupo Contínuo e por quatro períodos de 12 horas, alternados com 12 horas de descanso, no grupo intermitente. Os animais do grupo Controle foram submetidos ao implante do dispositivo de bandagem, o qual foi mantido desinsuflado. As medidas hemodinâmicas foram tomadas diariamente, antes e após o ajuste da sobrecarga sistólica. Avaliações ecocardiográficas foram realizadas no pré-operatório e no final do protocolo de estudo. Após 96 horas de estudo, os animais foram mortos para avaliação dos parâmetros morfológicos (peso e conteúdo de água das massas cardíacas e análise imuno-histoquímica da apoptose e da expressão do VEGF). Resultados: Ao final do protocolo, o ecocardiograma revelou uma diferença significativa da espessura do VD no grupo Intermitente (+129,2%), quando comparado ao grupo Contínuo (+58,2%; p < 0,001) e de ambos os grupos de estudo quando comparados ao grupo Controle (p < 0,001). Sob a análise morfológica, ambos os grupos de estudo apresentaram ganho de magnitude semelhante nas massas do VD (Intermitente: + 115,8%; Contínuo: + 90,8%; p < 0,0001) e do septo (Intermitente: +55,8%; Contínuo: + 45,4%; p < 0,047), em relação ao grupo Controle, apesar do menor tempo de sobrecarga pressórica no grupo Intermitente. O protocolo de sobrecarga sistólica do VD não influenciou a massa muscular do VE. Houve um discreto aumento do conteúdo de água do VD (Contínuo: +3,5%, Intermitente: +4,6%) e do septo (ambos os grupos de estudo: +3,5%) em relação ao grupo Controle (p < 0,002). A expressão do VEGF foi maior no VD do grupo Intermitente (2,89% ± 0,41%; p=0,005) em relação ao VD dos demais grupos (Controle: 1,43% ± 0,18%; Contínuo: 1,80% ± 0,19%). A expressão desta molécula no miocárdio do VD do grupo Intermitente foi também maior que o do VE e septo dentro do mesmo grupo (p < 0,050). Não houve diferença na expressão do VEGF das demais massas cardíacas (VE: p > 0,252; Septo: p > 0,740). Em relação à apoptose, não foram observadas diferenças significativas no miocárdio do VD dos três grupos (Caspase: p=0,784; TUNEL: p=0,374). Conclusões: Ambos os grupos de estudo desenvolveram hipertrofia miocárdica do VD, não acompanhada de edema miocárdico importante ou apoptose. No entanto, a sobrecarga sistólica intermitente promoveu maior expressão do VEGF no miocárdio do VD. Esta associação entre sinalização de proliferação vascular e hipertrofia tem implicações importantes quando se objetiva preparar um ventrículo para suportar pressões sistêmicas, uma vez que o desejável é que a proliferação vascular ocorra de forma sustentada, permitindo uma hipertrofia do VD mais eficiente / Introduction: Surgical correction of transposition of the great arteries beyond the neonatal period needs a previous pulmonary artery band to promote left ventricular hypertrophy thereby preparing the ventricle. Experimental studies have demonstrated that intermittent systolic overload causes a more efficient ventricular hypertrophy, as compared to traditional pulmonary artery banding. The adaptive mechanisms involved in the subpulmonary ventricle retraining are not completely established. Nevertheless, besides the hypertrophy and/or hyperplasia of the contractile cardiomyocytes, noncontractile cells (vascular and interstitial) from the stimulated ventricle also present structural phenotype changes. It remains unclear the ideal increasing rate of the myocardial interstitium as well as capillary vessel proliferation in the process of ventricular retraining before undertaking the arterial switch. Objective: This study sought to assess adaptive changes of the subpulmonary ventricle in regards to vascular endothelial growth factor (VEGF) expression and apoptosis in young goats submitted to continuous versus intermittent systolic overload by means of an adjustable pulmonary artery band. Methods: 21 young goats were separated into 3 groups: Control (no systolic overload), Continuous (96-hour continuous systolic overload), and Intermittent (four 12-hour periods of systolic overload paired with a 12-hour resting period). Systolic overload was adjusted to achieve a 0.7 RV / aortic pressure ratio. Hemodynamic evaluations were performed before and after systolic overload every day postoperatively. Echocardiograms were obtained preoperatively and at the end of protocol. After the study period, the animals were humanely killed for morphologic assessment, apoptosis and vascular endothelial growth factor (VEGF) expression. Results: Echocardiography revealed a marked increase in RV wall thickness in the Intermittent group (+129.2%), compared with the Continuous group (+58.2%; p<0.001), as well as both trained groups compared to Control group (p < 0.001). Regardless of the shorter systolic overload exposure of Intermittent group, both study groups had a similar increase in RV mass (Intermittent: + 115.8%; Continuous: +90.8%; p < 0.001), and septal mass (Intermittent: + 55.8%; Continuous: + 45.4%; p < 0.047), compared with the Control group. No significant changes in the left ventricle mass were seen. There was a negligible but significant increase in water content of RV (Continuous: +3.5%, Intermittent: +4.6%) and septal masses (both study groups: +3.5%) compared with that in the Control group (p < 0.002). RV VEGF expression was greater in the Intermittent group (2.89% ± 0.41%) than in the Continuous (1.80% ± 0.19%) and Control (1.43% ± 0.18%) groups (p < 0.023). VEGF expression in the myocardium of the right ventricle in the Intermittent group was also greater than that in the left ventricle and septum within the same group (p < 0.050). There was no significant difference in VEGF expression between the other cardiac sections or within the Control and Continuous groups. Regarding apoptosis, there were no significant changes in the RV myocardium of the three groups (Caspase: p=0,784; TUNEL: p=0,374). Conclusions: Both study groups have developed RV hypertrophy with no apoptosis or relevant myocardial edema. Nevertheless, intermittent systolic overload causes upregulation of VEGF expression in the subpulmonary ventricle, an adaptation that provides a mechanism for increased myocardial perfusion during the rapid myocardial hypertrophy of young goats. The association of the marked increase in RV mass and increased angiogenesis signaling has an important implication on the subpulmonary ventricle retraining protocol by promoting a compensatory growth of the coronary vasculature, allowing for a more efficient hypertrophy

O linfoma difuso de grandes células B (LDGCB) é o subtipo de linfoma mais comum em países em desenvolvimento. Entretanto, apesar de sua prevalência e importância, ainda existem poucas publicações com dados epidemiológicos para a população brasileira. Conhecer os fatores de prognóstico é imperativo para identificar os pacientes que responderão melhor ao tratamento, além de permitir sua individualização terapêutica. Alguns estudos demonstraram que pacientes com o mesmo Índice Internacional de Prognóstico (IPI) podem apresentar diferentes sobrevidas, justificando a necessidade de identificar novos marcadores biológicos de prognóstico. O objetivo deste estudo foi avaliar o impacto prognóstico da expressão dos genes BCL2, MDR1 e OCT1, de suas respectivas proteínas e da translocação t(14;18), nos desfechos de resposta completa (RC), sobrevida global (SG), sobrevida livre de doença (SLD) e sobrevida livre de progressão (SLP) em pacientes com LDGCB. Foram avaliados de forma retrospectiva 98 pacientes com LDGCB de novo tratados com R-CHOP. A expressão gênica foi avaliada por PCR em Tempo Real com RNA extraído de amostras parafinadas. A expressão proteica foi avaliada pelo método de imuno-histoquímica. A mediana de idade foi de 54,5 anos e 49 pacientes (50%) eram do sexo masculino. Sessenta e quatro pacientes (85,3%) obtiveram RC, com uma mediana de acompanhamento de 2,66 anos. A expressão mediana de BCL2, MDR1 e OCT1 foi 6,27; 0 e 24,49, respectivamente. Não encontramos impacto prognóstico da expressão do gene BCL2 na RC (p=0,277), SG (p=0,068) e SLD (p=0,860). Porém, a expressão de BCL2 >= à mediana associou-se à menor SLP (p=0,040). Encontramos associação entre expressão do gene OCT1 >= à mediana e pior prognóstico para SG (p=0,010) e SLP (p=0,016). Porém, não observamos impacto prognóstico da expressão de OCT1 para RC (p=0,464) e SLD (p=0,717). Não houve associação entre expressão do gene MDR1 e das proteínas BCL-2, Pg-p e OCT-1 com o prognóstico dos pacientes em relação à RC, SG, SLD e SLP. O número de sítios extralinfonodais (p=0,004 e p=0,005), estádio clínico (p < 0,001 para ambas), IPI (p < 0,001 para ambas) e nível de DHL (p=0,010 e p=0,008) apresentaram impacto prognóstico na SG e SLP, respectivamente. Quando os pacientes foram estratificados pelo estádio, IPI e idade, o grupo com expressão de OCT1 >= à mediana e IPI intermediário-alto ou alto risco apresentou pior SG (p=0,048) e o grupo com idade >= 60 anos e expressão de OCT1 >= à mediana apresentou pior prognóstico para SG e SLP (p=0,025 para ambas). Em conclusão, a expressão de MDR1 não apresentou impacto no prognóstico de portadores de LDGCB, porém, a expressão do gene BCL2 >= à mediana foi associada a menor SLP. Além disso, a hiperexpressão de OCT1 apresentou valor preditivo de prognóstico para a SG e SLP em pacientes com LDGCB tratados com R-CHOP / The diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma subtype in developing countries. However, despite its prevalence and importance, there are still few publications showing the epidemiological data of the Brazilian population. Knowing the prognostic factors is imperative to identify patients supposed to better respond to treatment, as well as to allow their therapeutic individualization. Some studies have shown that patients with the same International Prognostic Index (IPI) may present different survival rates, thus justifying the need to identify new prognosis biomarkers. The aim of this study was to assess the prognostic impact of the genes BCL2, MDR1 and OCT1 and their respective proteins and t (14; 18) translocation on the complete response (CR), overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS) of patients with DLBCL. We retrospectively assessed 98 patients with de novo DLBCL treated with R-CHOP. The gene expression was assessed through real-time PCR using RNA extracted from paraffin samples. The protein expression was assessed through the immunohistochemistry method. The median age was 54.5 years; 49 patients (50%) were men. Sixty-four patients (85.3%) had CR and median follow-up 2.66 years. The median expression of BCL2, MDR1 and OCT1 was 6.27; 0 and 24.49, respectively. We did not find the prognostic impact of the BCL2 gene expression on CR (p = 0.277), OS (p = 0.068) and on DFS (p = 0.860). However, the expression of BCL2 >= the median was associated with the lower PFS (p = 0.040). We found association between OCT1 gene expression >= the median and worse prognosis for OS (p = 0.010) and PFS (p = 0.016). However, we did not find the prognostic impact of OCT1 expression on CR (p = 0.464) and DFS (p = 0.717). There was no association between the MDR1 gene expression and the BCL-2, Pg-p and OCT-1 proteins, and the patients\' prognosis regarding CR, OS, DFS and PFS. The number of extranodal sites (p = 0.004 and p = 0.005), the clinical status (p <0.001 for both), the IPI (p < 0.001 for both) and DHL levels (p = 0.010 and p = 0.008) presented PFS, respectively. When the patients were stratified by stage, IPI and age, the group with OCT1 expression at the median and intermediate-to-high or high-risk IPI had worse OS results (p = 0.048) and the patients in the age group >= 60 years and expression of OCT1 >= the median presented worse prognosis for OS and PFS (p = 0.025 for both). Therefore, the MDR1 expression had no impact on the prognosis of DLBCL carriers. However, the expression of the BCL2 gene >= the median was associated with lower PFS. In addition, the OCT1 hyperexpression presented a predictive prognosis value for OS and PFS in patients with DLBCL treated with R-CHOP

O melhor comportamento de uma estrutura de solo reforçado com geossintéticos não depende só da elevada resistência à tração da inclusão, mas também da sua rigidez e do nível de carregamento sob o qual a estrutura está submetida. Dessa maneira, a interação entre o reforço e as respectivas camadas de solo ao seu redor torna-se de grande importância, pois a mobilização cisalhante combina a deformação da interface solo-reforço e o alongamento do geossintético. Sendo que a melhor forma de avaliar a interação entre o solo e a geogrelha é por meio de ensaios de arrancamento, pensa-se na realização de ensaios de arrancamento cíclico para analisar a interação dinâmica entre o solo e a inclusão quando certas estruturas são submetidas a esse tipo de solicitação. Por causa disso, o objetivo principal deste trabalho é analisar o efeito produzido por carregamentos monotônicos e cíclicos de interface numa geogrelha biaxial de polipropileno, quando inserida na interface de um solo argiloso e um solo arenoso sob diferentes tensões de confinamento. Para isso, são utilizados os equipamentos de pequenas e grandes dimensões do Laboratório de Geossintéticos da EESC-USP, visando avaliar a sua relação e a viabilidade de uso do equipamento de pequenas dimensões. Inicialmente foram realizados ensaios de arrancamento monotônico em ambos os equipamentos sob tensões de confinamento de 25, 50 e 100 kPa, sendo que as resistências obtidas com as tensões de 25 e 100 kPa permitiram definir as amplitudes do carregamento cíclico correspondentes ao 20% de tais valores. Adicionalmente, após a aplicação dos 10.000 ciclos de carga correspondentes à capacidade do equipamento, foi aplicado novamente um carregamento monotônico com o intuito de determinar o efeito do carregamento dinâmico na resistência ao arrancamento e assim poder realizar as respectivas comparações com os valores iniciais. Com base nos resultados obtidos, foi possível observar a diferença no grau de confinamento entre ambos os equipamentos, sendo maior no de grandes dimensões por causa da melhor distribuição das tensões sobre a área ocupada pela geogrelha. Adicionalmente, o grau de confinamento em ambos os equipamentos também influenciou a diferença no efeito do carregamento dinâmico, sendo de desconfinamento no de grandes dimensões e de densificação no de pequenas dimensões. / The best behavior of a reinforced soil structure with geosynthetics not only depends on the high tensile strength of the inclusion, but also on its rigidity and the loading level in which the structure is subjected. Thus, the interaction between the reinforcement and the respective layers of soil around, becomes very important because the shear mobilization combines the deformation of the soil-reinforcement interface and the lengthening of the geosynthetic. Since the best way to assess the soil-geogrid interaction is through pullout tests, it is thought in performing cyclic pullout tests to examine the dynamic soil-inclusion interaction when some structures are submitted to that kind of loads. Because of that, the main objective of this work is to analize the effect that is produced by monotonic and cyclic interface loading on a biaxial polypropylene geogrid, when it is inserted into the interface of a clayey soil and a sandy soil under different confinement stresses. For that, the small and large dimensions equipments of the Geosynthetics Laboratory at EESC-USP are used, looking to evaluate their relationship and the feasibility of using a small dimensions equipment. Initially, they were performed monotonic pullout tests in both equipments under confinement stresses of 25, 50 and 100 kPa, wherein the pullout strengths obtained with 25 and 100 kPa allowed the definition of the load cyclic amplitudes, which corresponded to 20% of such values. Additionally, after applying 10.000 load cycles, corresponding to the capacity of the equipment, it was applied a monotonic loading in order to determine the dynamic loading effect on pullout strength, being useful to compare such values with the initial response. Based on the obtained results, it was possible to observe the difference in the confinement degree between both equipments, being higher in the large one because of the better stress distribution on the geogrid area. Aditionally, the confinement degree in both equipments also influenced the difference in the dynamic loading effect, being deconfinement in the soil-geogrid interface of the large one and densification in the other one.

INTRODUÇÃO: O linfoma difuso de grandes células B, sem outras especificaçoes (LDGCB, SOE) é uma neoplasia agressiva caracterizada pela heterogeneidade morfológica, imunofenotípica e molecular, porém o atual tratamento padrão utilizando imunoquimioterapia (R-CHOP) não considera tal diversidade. Há percentual significativo de pacientes que são refratários à terapia de primeira linha e alguns que apresentam recidiva precoce ou tardia, os quais representam as vítimas desta doença. O estudo imuno-histoquímico (IHQ), que é um método simples e universalmente disponível, vem sendo utilizado para reconhecer a diversidade biológica do LDGCB, SOE, identificando biomarcadores e subgrupos distintos da doença, que poderiam predizer a resposta terapêutica ao tratamento padrão e apontar possíveis candidatos a novas estratégias terapêuticas. OBJETIVOS: Este estudo avalia o valor prognóstico de cinco algoritmos para classificação do LDGCB segundo a célula de origem (COO) e da expressão de três biomarcadores (BCL2, CD30 e MYC) tendo como endpoint a sobrevida global. MÉTODOS: Foi realizado estudo retrospectivo com setenta e nove pacientes com LDGCB,SOE de novo tratados com imunoquimioterapia padrão, estadiados e acompanhados protocolarmente. Os casos foram classificados como subgrupo célula B centrogerminativa símile (GCB) ou como subgrupo célula B não-centrogerminativa símile (NGCB), de acordo com três algoritmos IHQ (Hans, Choi, e Visco-Young) pareados com estudo do perfil de expressão gênica (PEG) e dois algoritmos IHQ não-PEG pareados (Muris e Nyman). Foi estimado o valor prognóstico destes algoritmos e também avaliado a concordância entre eles. O valor prognóstico da expressão do BCL2, CD30 e MYC utilizando IHQ também foi analisado. RESULTADOS: Os algoritmos IHQ PEG pareados revelaram maior concordância entre si, porém nenhum deles revelou força prognóstica. A expressão do CD30 mostrou tendência a melhor prognóstico, porém a expressão de BCL2 e MYC avaliados isoladamente não revelaram impacto prognóstico. Contudo, a coexpressão do BCL2 e MYC, denominado como fenótipo linfoma duplo-expressor (LDE), revelou-se importante marcador prognóstico desfavorável. Foram identificados três subgrupos de risco baseado no fenótipo LDE e o Índice Prognóstico Internacional (IPI). CONCLUSÃO: Em pacientes com LDGCB, SOE de novo tratados com esquema terapêutico padrão, a pesquisa da expressão do fenótipo LDE é mais relevante do ponto vista prognóstico que a classificação em subgrupo GCB ou NGCB. Além disso, a expressão do CD30 pode ser relevante tanto para identificar subgrupo com tendência a melhor prognóstico como para identificar possíveis candidatos a nova terapia alvo / BACKGROUND: Diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS) is an aggressive neoplasm characterized by morphological, phenotypic and molecular heterogeneity, but the current standard therapy using immunochemotherapy (R-CHOP) does not consider such diversity. There is a significant percentage of patients who are refractory to first-line therapy and those with early or late recurrence, whose represent the victims of this disease. Immunohistochemistry (IHC), a simple and universally available method, has been used to recognize the biological diversity of DLBCL, NOS, to identify biomarkers and distinct subgroups of the disease, which would predict the therapeutic response to standard treatment and point possible candidates for novel therapeutic strategies. OBJECTIVES: The current study was conducted to evaluate the prognostic value from five algorithms for classification of DLBCL based on cell of origin (COO) and the expression of three biomarkers (BCL2, CD30 and MYC) with overall survival (OS) as an endpoint. METHODS: We retrospectively evaluated seventy nine patients with de novo DLBCL, NOS treated with R-CHOP-like immunochemotherapy. The cases were assigned as germinal center B-cell like (GCB) or non-GCB subgroup (NGCB) according to five different IHC algorithms, including three algorithms based on gene expressing profile study (GEP), proposed by Hans, Choi, and Visco-Young, and two non-GEP based algoritms proposed by Muris, and Nyman. We evaluated their prognostic relevance and the concordance between these algorithms. The prognostic power of BCL2, CD30 and MYC expression were also assessed by IHC. RESULTS: None of the profiles assessed by IHC algorithms was able to predict overall survival (OS). The positive expression of CD30 showed a trend toward a better outcome. Neither the positive expression of BCL2 nor the positive expression of MYC were associated with outcome. However, the double-expressor lymphoma phenotype (DEL), represented by the concurrent expression of MYC and BCL2, exhibited a negative prognostic impact. Three different risk subgroups were identified based on the DEL phenotype and the International Prognostic Index (IPI) score. CONCLUSIONS: These data suggest that the DEL, rather than the cell of origin classification based on IHC, is a better predictor of OS in patients with DLBCL treated with R-CHOP-like immunochemotherapy. Besides, the CD30 expression may be a useful prognostic marker and a possible therapeutic target

L’étude présentée dans cette thèse relève de la mécanique des fluides expérimentale et numérique appliquée aux écoulements pariétaux de refroidissement de chambres de combustion aéronautiques. En présence de phénomènes thermo-acoustiques, comme les instabilités de combustion, il est important d’évaluer si les capacités de l’écoulement pariétal à protéger les parois de chambre restent suffisantes. C’est ainsi que nous nous sommes intéressés aux écoulements de paroi multiperforée soumis à une excitation acoustique. Dans ce but, le banc d’essais MAVERIC a été amélioré grâce à l’installation d’un système qui permet de forcer acoustiquement l’écoulement transverse dans lequel les jets pariétaux débouchent. Nous avons pu alors mettre en évidence la forte sensibilité de ce type d’écoulements à l’excitation acoustique. Le bon accord entre les résultats expérimentaux et les simulations numériques aux grandes échelles (LES) effectuées est très encourageant dans le cas d’un forçage par onde stationnaire. Le forçage par onde progressive, étudié uniquement par simulations numériques, s’est révélé être capable de modifier significativement la topologie de l’écoulement. Enfin, à partir de l’outil numérique AVBP-AVTP qui permet le couplage de calculs fluide-solide, nous avons réalisé une étude de l’influence de la présence d’une excitation acoustique sur le comportement thermique de l’écoulement autour d’une paroi multiperforée de chambre de combustion. / This experimental and numerical study in the field of fluid mechanics deals with jets-in cross flow configurations that are relevant for the cooling of aero engine combustion chambers. Indeed, in presence of instabilities it is important to determine to which extent the film cooling is able to do its job of preserving the combustion chamber walls from the thermal load. The test facility MAVERIC has been upgraded in order to acoustically force the crossflow in which the jets are discharging. The strong sensitivity of the overall flow unsteady properties to the presence of the acoustic forcing has been clearly evidenced. The agreement between the experimental results and large-eddy simulations proved to be quite encouraging for a stationary acoustic wave whereas the case of a propagating acoustic wave investigated only numerically reveals also quite a significant change of the flow topology. In this context, the effect of the acoustic forcing on the wall thermal behavior has been analyzed thanks to the use of the fluid-solid coupled AVBP-AVTP solver.

L’objectif de ce travail porte sur le développement d’un modèle d’interaction fluide-structure adapté à la dynamique des éoliennes de grandes tailles avec des pales flexibles qui se déforment de manière significative sous l’effet de la pression exercée par le vent. Le modèle développé est basé sur une approche efficace d’IFS partitionnée pour un fluide incompressible et non visqueux en interaction avec une structure flexible soumise a des grandes transformations. Il permet de fournir une meilleure estimation de la charge aérodynamique et de la réponse dynamique associée du système (pales, mat, attachements, câbles) avec un temps de calcul raisonnable et pour des simulations sur des longues périodes. Pour la modélisation structurale, un élément fini de type solide 3D est développé pour l’étude dynamique des pales d’éolienne soumises à des grands déplacements et des grandes rotations. Une amélioration du comportement en flexion est proposée par l’introduction des degrés de liberté en rotation et l’enrichissement du champ de déplacements afin de décrire plus précisément la flexibilité des pales. Cet élément solide est apte de capter des modes de hautes fréquences qui peuvent s’avérer néfastes pour la stabilité du calcul. Deux techniques sont donc proposées pour les contrôler : la régularisation de la matrice masse et le développement des schémas d’intégration robustes de conservation et de dissipation d’énergie. Les chargements aérodynamiques sont modélisés en utilisant la Panel Method. Il s’agit d’une méthode aux frontières, relativement rapide par rapport à la CFD mais suffisamment précise pour calculer la distribution de la pression exercée sur la pale. Les modèles fluide et structure interagissent via un algorithme de couplage partitionné itératif dans lequel des considérations particulières sont prises en compte dans le contexte des grandes transformations. Dans un effort visant à instaurer un indicateur de fatigue dans la méthodologie proposée, des câbles précontraints sont introduits reliant le mat de l’éolienne au support. Une nouvelle formulation complémentaire en termes de contraintes est ainsi développée pour l’analyse dynamique des câbles 3D en comportement élasto-visco-plastique. Chaque méthode proposée a été d’abord validée sur des cas tests pertinents. Par la suite, des simulations numériques d’éoliennes avec des pales flexibles sont effectuées en vue d’affiner la compréhension de leur comportement dynamique et l’intérêt que la flexibilité des pales peut apporter à leur fonctionnement. / In this work, a numerical model of fluid-structure interaction is developed for dynamic analysis of giant wind turbines with flexible blades that can deflect significantly under wind loading. The model is based on an efficient partitioned FSI approach for incompressible and inviscid flow interacting with a flexible structure undergoing large transformations. It seeks to provide the best estimate of true design aerodynamic load and the associated dynamic response of such system (blades, tower, attachments, cables). To model the structure, we developed a 3D solid element to analyze geometrically nonlinear statics and dynamics of wind turbine blades undergoing large displacements and rotations. The 3D solid bending behavior is improved by introducing rotational degrees of freedom and enriching the approximation of displacement field in order to describe the flexibility of the blades more accurately. This solid iscapable of representing high frequencies modes which should be taken under control. Thus, we proposed a regularized form of the mass matrix and robust time-stepping schemes based on energy conservation and dissipation. Aerodynamic loads are modeled by using the 3D Vortex Panel Method. Such boundary method is relatively fast to calculate pressure distribution compared to CFD and provides enough precision. The aerodynamic and structural parts interact with each other via a partitioned coupling scheme with iterative procedure where special considerations are taken into account for large overall motion. In an effort to introduce a fatigue indicator within the proposed framework, pre-stressed cables are added to the wind turbine, connecting the tower to the support and providing more stability. Therefore, a novel complementary force-based finite element formulation is constructed for dynamic analysis of elasto-viscoplastic cables. Each of theproposed methods is first validated with differents estexamples.Then,several numerical simulations of full-scale wind turbines are performed in order to better understand its dynamic behavior and to eventually optimize its operation.