Ce travail de thèse porte sur l’analyse robuste et l’optimisation fiabiliste des problèmes vibro-acoustiques (ou en interaction fluide-structure) en tenant en compte des incertitudes des paramètres d’entrée. En phase de conception et de dimensionnement, il parait intéressant de modéliser les systèmes vibro-acoustiques ainsi que leurs variabilités qui peuvent être essentiellement liées à l’imperfection de la géométrie ainsi qu’aux caractéristiques des matériaux. Il est ainsi important, voire indispensable, de tenir compte de la dispersion des lois de ces paramètres incertains afin d’en assurer une conception robuste. Par conséquent, l’objectif est de déterminer les capacités et les limites, en termes de précision et de coûts de calcul, des méthodes basées sur les développements en chaos polynomiaux en comparaison avec la technique référentielle de Monte Carlo pour étudier le comportement mécanique des problèmes vibro-acoustique comportant des paramètres incertains. L’étude de la propagation de ces incertitudes permet leur intégration dans la phase de conception. Le but de l’optimisation fiabiliste Reliability-Based Design Optimization (RBDO) consiste à trouver un compromis entre un coût minimum et une fiabilité accrue. Par conséquent, plusieurs méthodes, telles que la méthode hybride (HM) et la méthode Optimum Safety Factor (OSF), ont été développées pour atteindre cet objectif. Pour remédier à la complexité des systèmes vibro-acoustiques comportant des paramètres incertains, nous avons développé des méthodologies spécifiques à cette problématique, via des méthodes de méta-modèlisation, qui nous ont permis de bâtir un modèle de substitution vibro-acoustique, qui satisfait en même temps l’efficacité et la précision du modèle. L’objectif de cette thèse, est de déterminer la meilleure méthodologie à suivre pour l’optimisation fiabiliste des systèmes vibro-acoustiques comportant des paramètres incertains. / This PhD thesis deals with the robust analysis and reliability optimization of vibro-acoustic problems (or fluid-structure interaction) taking into account the uncertainties of the input parameters. In the design and dimensioning phase, it seems interesting to model the vibro-acoustic systems and their variability, which can be mainly related to the imperfection of the geometry as well as the characteristics of the materials. It is therefore important, if not essential, to take into account the dispersion of the laws of these uncertain parameters in order to ensure a robust design. Therefore, the purpose is to determine the capabilities and limitations, in terms of precision and computational costs, of methods based on polynomial chaos developments in comparison with the Monte Carlo referential technique for studying the mechanical behavior of vibro-acoustic problems with uncertain parameters. The study of the propagation of these uncertainties allows their integration into the design phase. The goal of the reliability-Based Design Optimization (RBDO) is to find a compromise between minimum cost and a target reliability. As a result, several methods, such as the hybrid method (HM) and the Optimum Safety Factor (OSF) method, have been developed to achieve this goal. To overcome the complexity of vibro-acoustic systems with uncertain parameters, we have developed methodologies specific to this problem, via meta-modeling methods, which allowed us to build a vibro-acoustic surrogate model, which at the same time satisfies the efficiency and accuracy of the model. The objective of this thesis is to determine the best methodology to follow for the reliability optimization of vibro-acoustic systems with uncertain parameters.

Cette thèse développe une méthodologie originale et non intrusive de construction de modèles de substitution applicable à des modèles physiques multiparamétriques.La méthodologie proposée permet d’approcher en temps réel, sur l’ensemble du domaine paramétrique, de multiples quantités d’intérêt hétérogènes issues de modèles physiques.Les modèles de substitution sont basés sur des représentations en train de tenseurs obtenues lors d'une phase hors ligne de calculs intensifs.L'idée essentielle de la phase d'apprentissage est de construire simultanément les approximations en se basant sur un nombre limité de résolutions du modèle physique lancées à la volée.L'exploration parcimonieuse du domaine paramétrique couplée au format compact de train de tenseurs permet de surmonter le fléau de la dimension.L'approche est particulièrement adaptée pour traiter des modèles présentant un nombre élevé de paramètres définis sur des domaines étendus.Les résultats numériques sur des lois élasto-viscoplastiques non linéaires montrent que des modèles de substitution compacts en mémoire qui approchent précisément les différentes variables mécaniques dépendantes du temps peuvent être obtenus à des coûts modérés.L'utilisation de tels modèles exploitables en temps réel permet la conception d'outils d'aide à la décision destinés aux experts métiers dans le cadre d'études paramétriques et visent à améliorer la procédure de calibration des lois matériaux. / This thesis presents a novel non-intrusive methodology to construct surrogate models of parametric physical models.The proposed methodology enables to approximate in real-time, over the entire parameter space, multiple heterogeneous quantities of interest derived from physical models.The surrogate models are based on tensor train representations built during an intensive offline computational stage.The fundamental idea of the learning stage is to construct simultaneously all tensor approximations based on a reduced number of solutions of the physical model obtained on the fly.The parsimonious exploration of the parameter space coupled with the compact tensor train representation allows to alleviate the curse of dimensionality.The approach accommodates particularly well to models involving many parameters defined over large domains.The numerical results on nonlinear elasto-viscoplastic laws show that compact surrogate models in terms of memory storage that accurately predict multiple time dependent mechanical variables can be obtained at a low computational cost.The real-time response provided by the surrogate model for any parameter value allows the implementation of decision-making tools that are particularly interesting for experts in the context of parametric studies and aim at improving the procedure of calibration of material laws.

L’optimisation de la performance des voiliers est un problème difficile en raison de la complexité du systèmemécanique (couplage aéro-élastique et hydrodynamique) et du nombre important de paramètres à optimiser (voiles, gréement,etc.). Malgré le fait que l’optimisation des voiliers est empirique dans la plupart des cas aujourd’hui, les approchesnumériques peuvent maintenant devenir envisageables grâce aux dernières améliorations des modèles physiques et despuissances de calcul. Les calculs aéro-hydrodynamiques restent cependant très coûteux car chaque évaluation demandegénéralement la résolution d’un problème non linéaire d’interaction fluide-structure. Ainsi, l’objectif central de cette thèseest de proposer et développer des méthodes originales dans le but de minimiser le coût numérique de l’optimisation dela performance des voiliers. L’optimisation globale par méta-modèles Gaussiens est utilisée pour résoudre différents problèmesd’optimisation. La méthode d’optimisation par méta-modèles est étendue aux cas d’optimisations sous contraintes,incluant de possibles points non évaluables, par une approche de type classification. L’utilisation de méta-modèles à fidélitésmultiples est également adaptée à la méthode d’optimisation globale. Les applications concernent des problèmesd’optimisation originaux où la performance est modélisée expérimentalement et/ou numériquement. Ces différentes applicationspermettent de valider les développements des méthodes d’optimisation sur des cas concrets et complexes, incluantdes phénomènes d’interaction fluide-structure. / Sailing yacht performance optimization is a difficult problem due to the high complexity of the mechanicalsystem (aero-elastic and hydrodynamic coupling) and the large number of parameters to optimize (sails, rigs, etc.).Despite the fact that sailboats optimization is empirical in most cases today, the numerical optimization approach is nowconsidered as possible because of the latest advances in physical models and computing power. However, these numericaloptimizations remain very expensive as each simulation usually requires solving a non-linear fluid-structure interactionproblem. Thus, the central objective of this thesis is to propose and to develop original methods aiming at minimizing thenumerical cost of sailing yacht performance optimization. The Efficient Global Optimization (EGO) is therefore appliedto solve various optimization problems. The original EGO method is extended to cases of optimization under constraints,including possible non computable points, using a classification-based approach. The use of multi-fidelity surrogates isalso adapted to the EGO method. The applications treated in this thesis concern the original optimization problems inwhich the performance is modeled experimentally and/or numerically. These various applications allow for the validationof the developments in optimization methods on real and complex problems, including fluid-structure interactionphenomena.

Made available in DSpace on 2016-04-29T13:18:17Z (GMT). No. of bitstreams: 1 Bruno Cesar de Pinho Costa.pdf: 2100325 bytes, checksum: a0a403a0fe937f1bb60b8c8668abe43d (MD5) Previous issue date: 2010-04-29 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / This study sought to: (1) propose a device to the experimental analysis of behavior, (2) present the results of two studies conducted during the testing of equipment, (3) present the first experimental results obtained from monitoring the daily activities of the experimental subject in such equipment and (4) report two experiments in which they attempted to demonstrate empirically the establishment of different surrogate conditioned motivating operations. First, the equipment (Caixa Geradora e Monitora de Cotidiano, CGMC) was presented. During testing of the equipment, two studies were conducted. The first on the effects of light on the daily activities of the experimental subject, the results produced indicated the need for adjustments to equipment, in particular concerning the type and intensity of light used for establishing the cycles of light / dark. The second study occurred during the tests CGMC allowed us to analyze the effects of water restriction (imposed accidentally) of approximately five days on the daily activities of the experimental subject. The results indicate changes in the distribution of the daily activities of the experimental subjects, even those not necessarily related to obtaining water. Once the testing phase of the equipment was finished, a study was conducted in order to monitor the daily activities of the experimental subjects, over the days. The results point to the existence of patterns in the flow behavior that can be modified by various types of variables, such as the cycle of light and dark used, water restrictions and changes in schedules of reinforcement. Finally, two experiments were performed in order to demonstrate empirically the formation of two surrogate conditioned motivating operations. The results point to the failure to establish surrogate conditioned motivating operations / O presente trabalho pretendeu: (1) apresentar uma proposta de equipamento para a análise do comportamento, (2) apresentar os resultados de dois estudos realizados durante os testes do equipamento, (3) apresentar os primeiros resultados experimentais obtidos a partir do monitoramento das atividades diárias do sujeito experimental neste tipo equipamento e (4) relatar dois experimentos nos quais se tentou demonstrar empiricamente o estabelecimento de diferentes operações motivadoras condicionadas substituas. Primeiramente, o equipamento (Caixa Geradora e Monitora de Cotidiano, CGMC) foi apresentado. Durante os testes do equipamento, dois estudos foram realizados. O primeiro sobre os efeitos das luzes sobre as atividades diárias do sujeito experimental; os resultados produzidos indicaram a necessidade de ajustes no equipamento, em especial com relação ao tipo e intensidade da luz utilizada para estabelecer os ciclos de claro/escuro. O segundo estudo ocorrido durante os testes da CGMC permitiu analisar os efeitos de uma restrição hídrica (acidentalmente imposta) de aproximadamente cinco dias de duração sobre as atividades diárias do sujeito experimental. Os resultados apontam para mudanças na distribuição das atividades diárias do sujeito experimental, mesmo daquelas não necessariamente relacionadas com a obtenção de água. Concluída a fase de testes do equipamento, foi realizado um estudo com o objetivo monitorar as atividades diárias do sujeito experimental, ao longo dos dias. Os resultados obtidos apontam para a existência de padrões no fluxo comportamental que podem ser modificados por diversos tipos de variáveis, como o ciclo de claro-escuro utilizado, restrições hídricas e mudanças nos esquemas de reforçamento. Por fim, dois experimentos foram realizados com o objetivo de se demonstrar empiricamente a formação de duas operações motivadoras condicionas substitutas. Os resultados apontam para o não estabelecimento das operações motivadoras condicionadas substitutas

Le contrôle non destructif électromagnétique (CNDE) est appliqué dans des domaines variés pour l'exploration de défauts cachés affectant des structures. De façon générale, le principe peut se poser en ces termes : un objet inconnu perturbe un milieu hôte donné et illuminé par un signal électromagnétique connu, et la réponse est mesurée sur un ou plusieurs récepteurs de positions connues. Cette réponse contient des informations sur les paramètres électromagnétiques et géométriques des objets recherchés et toute la difficulté du problème traité ici consiste à extraire ces informations du signal obtenu. Plus connu sous le nom de « problèmes inverses », ces travaux s'appuient sur une résolution appropriée des équations de Maxwell. Au « problème inverse » est souvent associé le « problème direct » complémentaire, qui consiste à déterminer le champ électromagnétique perturbé connaissant l'ensemble des paramètres géométriques et électromagnétiques de la configuration, défaut inclus. En pratique, cela est effectué via une modélisation mathématique et des méthodes numériques permettant la résolution numérique de tels problèmes. Les simulateurs correspondants sont capables de fournir une grande précision sur les résultats mais à un coût numérique important. Sachant que la résolution d'un problème inverse exige souvent un grand nombre de résolution de problèmes directs successifs, cela rend l'inversion très exigeante en termes de temps de calcul et de ressources informatiques. Pour surmonter ces challenges, les « modèles de substitution » qui imitent le modèle exact peuvent être une solution alternative intéressante. Une manière de construire de tels modèles de substitution est d'effectuer un certain nombre de simulations exactes et puis d'approximer le modèle en se basant sur les données obtenues. Le choix des simulations (« prototypes ») est normalement contrôlé par une stratégie tirée des outils de méthodes de « plans d'expérience numérique ». Dans cette thèse, l'utilisation des techniques de modélisation de substitution et de plans d'expérience numérique dans le cadre d'applications en CNDE est examinée. Trois approches indépendantes sont présentées en détail : une méthode d'inversion basée sur l'optimisation d'une fonction objectif et deux approches plus générales pour construire des modèles de substitution en utilisant des échantillonnages adaptatifs. Les approches proposées dans le cadre de cette thèse sont appliquées sur des exemples en CNDE par courants de Foucault / Electromagnetic Nondestructive Evaluation (ENDE) is applied in various industrial domains for the exploration of hidden in-material defects of structural components. The principal task of ENDE can generally be formalized as follows: an unknown defect affects a given host structure, interacting with a known electromagnetic field, and the response (derived from the electromagnetic field distorted by the defect) is measured using one or more receivers at known positions. This response contains some information on the electromagnetic constitutive parameters and the geometry of the defect to be retrieved. ENDE aims at extracting this information for the characterization of the defect, i.e., at the solution of the arising “inverse problem”. To this end, one has to be able to determine the electromagnetic field distorted by a defect with known parameters affecting a given host structure, i.e., to solve the “forward problem”. Practically, this is performed via the mathematical modeling (based on the Maxwell's equations) and the numerical simulation of the studied ENDE configuration. Such simulators can provide fine precision, but at a price of computational cost. However, the solution of an inverse problem often requires several runs of these “expensive-to-evaluate” simulators, making the inversion procedure firmly demanding in terms of runtime and computational resources. To overcome this challenge, “surrogate modeling” offers an interesting alternative solution. A surrogate model imitates the true model, but as a rule, it is much less complex than the latter. A way to construct such surrogates is to perform a couple of simulations and then to approximate the model based on the obtained data. The choice of the “prototype” simulations is usually controlled by a sophisticated strategy, drawn from the tools of “design-of-experiments”. The goal of the research work presented in this Dissertation is the improvement of ENDE methods by using surrogate modeling and design-of-experiments techniques. Three self-sufficient approaches are discussed in detail: an inversion algorithm based on the optimization of an objective function and two methods for the generation of generic surrogate models, both involving a sequential sampling strategy. All approaches presented in this Dissertation are illustrated by examples drawn from eddy-current nondestructive testing.

Excision Repair Cross-Complementation group 1 (ERCC1) est une enzyme de réparation de l’ADN fréquemment déficiente dans le cancer bronchique non-à-petites cellules. Bien qu’une expression faible d’ERCC1 soit prédictive de réponse aux sels de platine, l’efficacité des chimiothérapies à base de platine est limitée par leur toxicité et l’apparition de résistance, justifiant la nécessité de stratégies thérapeutiques alternatives. Par ailleurs, l’absence de test compagnon diagnostic permettant d’évaluer la fonctionnalité d’ERCC1 dans la pratique clinique empêche actuellement toute thérapie personnalisée basée sur le statut ERCC1.Afin d’identifier de nouvelles stratégies thérapeutiques pour les tumeurs ERCC1-déficientes en exploitant le concept de létalité synthétique, des screens à haut-débit , utilisant des composés pharmaceutiques ou par ARN interférence, ont été réalisés dans un modèle isogénique de CBNPC déficient en ERCC1. Cette approche a permis d’identifier plusieurs inhibiteurs de poly(ADP-ribose) polymerase 1 et 2 (PARP1/2), tels l’opalarib (AZD2281), le niraparib (MK-24827) et BMN 673 comme sélectifs pour les cellules ERCC1-déficientes. Les mécanismes sous-tendant cette sensibilité sélective ont été étudiés, et les résultats suivants ont été mis en évidence : (i) les cellules ERCC1-déficientes présentent un blocage prolongé en phase G2/M après exposition à l’olaparib ; (ii) l’isoforme 202 d’ERCC1, dont le rôle a été récemment mis en évidence dans la résistance aux sels de platine, module également la sensibilité aux inhibiteurs de PARP ; (iii) la déficience en ERCC1 est épistatique avec les défauts de recombinaison homologue (RH), malgré une capacité normale des cellules ERCC1-déficientes à former des foyers RAD51 ; ceci suggère qu’ERCC1 pourrait intervenir dans la réparation d’une lésion de l’ADN induite par l’inhibiteur de PARP1/2 en amont de l’invasion du brin d’ADN lors de la RH ; (iv) l’inhibition de l’expression de PARP1 par ARN interférence permet de restaurer la résistance aux inhibiteurs de PARP1/2, dans les cellules ERCC1-déficientes uniquement. Ces résultats suggèrent que les inhibiteurs de PARP1/2 pourraient représenter une nouvelle stratégie thérapeutique chez les patients dont la tumeur est déficiente en ERCC1 et un essai clinique va être mis en place pour évaluer cette hypothèse.Afin d’explorer la présence de biomarqueurs de la fonctionnalité d’ERCC1, quatre approches ont été entreprises en parallèle dans le modèle isogénique de CBNPC déficient en ERCC1: (i) irradiation aux UV, afin d’évaluer la voie NER (Nucleotide Excision Repair); (ii) séquençage d’exome, dans le but de rechercher une signature génomique (ADN) ; (iii) analyse du transcriptome cellulaire, pour identifier des modifications d’expression d’ARN ; et (iv) SILAC (Stable Isotope Labeling by Amino acids in Cell culture) afin de comparer le protéome des cellules ERCC1-déficientes et ERCC1-proficientes. Ces approches ont permis d’identifier une potentielle signature génomique, ainsi que de biomarqueurs d’activité – guanine deaminase (GDA) et nicotinamide phosphoribosyltransferase (NAMPT). De plus amples validations et investigations mécanistiques de ces observations préliminaires sont actuellement requises. / Excision Repair Cross-Complementation group 1 (ERCC1) is a DNA repair enzyme that is frequently deficient in non-small cell lung cancer (NSCLC). Although low ERCC1 expression correlates with platinum sensitivity, the clinical effectiveness of platinum therapy is limited - mainly by toxicities and occurrence of resistance - highlighting the need for alternative treatment strategies. In addition, the lack of a reliable assay evaluating ERCC1 functionality in the clinical setting currently precludes personalising therapy based on ERCC1 status. To discover new synthetic lethality-based therapeutic strategies for ERCC1-defective tumours, high-throughput drug and siRNA screens in an isogenic NSCLC model of ERCC1 deficiency were performed. This approach identified multiple clinical poly(ADP-ribose) polymerase 1 and 2 (PARP1/2) inhibitors such as olaparib (AZD-2281), niraparib (MK-4827) and BMN 673 as being selective for ERCC1 deficiency. The mechanism underlying ERCC1-selective effects was dissected by studying molecular biomarkers of tumour cell response, and revealed that: (i) ERCC1-deficient cells displayed a significant delay in double-strand break repair associated with a profound and prolonged G2/M arrest following PARP1/2 inhibitor treatment; (ii) ERCC1 isoform 202, which has recently been shown to mediate platinum sensitivity, also modulated PARP1/2 sensitivity; (iii) ERCC1-deficiency was epistatic with homologous recombination deficiency, although ERCC1-deficient cells did not display a defect in RAD51 foci formation. This suggests that ERCC1 might be required to process PARP1/2 inhibitor induced DNA lesions prior to DNA strand invasion; and (iv) PARP1 silencing restored PARP1/2 inhibitor resistance in ERCC1-deficient cells but had no effect in ERCC1-proficient cells, supporting the hypothesis that PARP1 might be required for the ERCC1 selectivity of PARP1/2 inhibitors. This study indicated that PARP1/2 inhibitors as a monotherapy could represent a novel therapeutic strategy for NSCLC patients with ERCC1-deficient tumours, and a clinical protocol is being written to evaluate this hypothesis.To investigate whether a surrogate biomarker of ERCC1 functionality could be developed, four parallel approaches were undertaken in the ERCC1-isogenic NSCLC model: (i) UV irradiation, to evaluate the Nucleotide Excision Repair (NER) pathway; (ii) whole exome sequencing, to look for an ERCC1-associated genomic scar at the DNA level; (iii) transcriptomic analysis, to investigate changes at the RNA expression level; and (iv) SILAC (Stable Isotope Labeling by Amino acids in Cell culture) analysis, to compare proteomic profiles between ERCC1-proficient and ERCC1-deficient cells. These approaches allowed the identification of putative genomic signature and potential metabolic surrogate biomarkers - guanine deaminase (GDA) and nicotinamide phosphoribosyltransferase (NAMPT). Further validation and mechanistic investigations of these latter preliminary observations are warranted.

“Daigou” (代購), a term originally from mainland China, has become a robust industry and novel business model in China for a few years with the market expanding 19 times between 2008 and 2012. Due to government intervention and trust-related problems, Daigou market size has been in decline since 2014 with sales volume of only about 40 billion CNY in 2015 (as compared to 57 billion CNY in 2014). In order to fully understand what Daigou is and how it works, this paper focuses on the Chinese market. The Thesis not only investigates many aspects of the Daigou industry including its key elements, target products, customer groups, market potentials, development trends, and influences, but also sums up all information about the current Daigou market in China and to analyze how its future may be. As Daigou business grows from startup to maturity, different problems and opportunities arise, demanding different business solutions. The change of business models is necessary to suit today’s market needs because what worked a year ago might no longer be the best approach nowadays. The evolution of Daigou is presented by making use of five major business models to show how each business model changed to keep up with the market. The impacts of diverse factors on different business models and to the individuals, community and other businesses, are also covered with the use of literature review, personal interviews and qualitative research.

Submitted by Silvana Teresinha Dornelles Studzinski (sstudzinski) on 2017-03-03T15:48:43Z No. of bitstreams: 1 Ida Beatriz de Luca_.pdf: 5910574 bytes, checksum: 2b2ca8a5fa1f0adb7cd1dd025ef08b76 (MD5) / Made available in DSpace on 2017-03-03T15:48:44Z (GMT). No. of bitstreams: 1 Ida Beatriz de Luca_.pdf: 5910574 bytes, checksum: 2b2ca8a5fa1f0adb7cd1dd025ef08b76 (MD5) Previous issue date: 2017-01-05 / Nenhuma / O Direito Contratual passou por diversas fases, estando inserido em um contexto onde cada vez mais a técnica traz desafios aos operadores do Direito. Através das cláusulas gerais há a possibilidade de incorporação de situações novas, possibilitando o ajustamento das consequências jurídicas a esses novos fatos sociais. O objetivo geral da tese foi estudar o contrato na realidade atual, especialmente quanto à questão da autonomia privada nos contratos de gestação de substituição, vinculado aos princípios constitucionais, no âmbito das possibilidades jurídicas trazidas pelo horizonte hermenêutico da comparação entre o Direito Brasileiro e o Direito dos Estados Unidos da América. O papel do intérprete passou a ser mais significativo, delimitando o alcance da norma através da interpretação, buscando o significado de algumas expressões tal como função social, na Constituição Federal e no diálogo com outras fontes do Direito. Na perspectiva da metodologia fenomenológico-hermenêutica que sustenta esta Tese, se pode afirmar que o intérprete tem cada vez mais responsabilidade pela atribuição criativa de sentido às cláusulas gerais que estão nos textos regulatórios pertinentes. A evolução da técnica trouxe novos desafios aos operadores do Direito. Neste contexto, a ausência de legislação no Brasil para os casos de gestação de substituição gera situações problemáticas para todos os envolvidos: a gestante de susbtituição, os pais intencionais e mesmo a comunidade médica. Diante da referida ausência legislativa para regular as relações dessa natureza, o Conselho Federal de Medicina editou uma resolução restringindo o Direito das partes envolvidas nestes acordos. A hipótese apresentada está na ressignificação da autonomia privada das partes envolvidas nos acordos de gestação de substituição, resguardando a dignidade da pessoa humana nessas relações contratuais, bem como os Princípios Fundamentais do Direito, alinhando ainda o Sistema Constitucional e o Sistema Internacional dos Direitos Humanos, relacionados ao tema, no panorama da fusão de horizontes entre o Direito Nacional e Direito Estrangeiro. Concluiu-se que tal resolução não pode restringir Direitos Fundamentais Individuais constitucionalmente protegidos, tal como o direito de liberdade, que neste caso pode ser entendido como a livre escolha de querer gestar um embrião para outra pessoa. Com relação ao Direito Contratual brasileiro, o modelo de contrato que mais se aproxima aos acordos de gestação de substituição é o contrato de prestação de serviços, porém destaca-se que neste caso existem peculiaridades a serem observadas em decorrência do tipo de atividade que será prestada. Em razão disso, há necessidade de avaliar a real autonomia da vontade da futura gestante de substituição, uma vez que existe Direito de Personalidade envolvido neste negócio jurídico. Neste sentido, a legislação pátria tem permitido uma relativização do caráter de indisponibilidade dos Direitos de Personalidade o que demonstra serem plenamente lícitos os contratos de gestação de substituição, mesmo de caráter oneroso, desde que as partes estejam exercendo sua real autonomia privada. Objetivando a criação de um modelo normativo de contrato de gestação de substituição para a ser utilizado no Brasil, foi efetuado um estudo de direito comparado utilizando-se a legislação e a análise de casos em três Estados dos Estados Unidos da América, buscando na experiência do Direito alienígena a possibilidade de, através do diálogo entre as fontes de direito estrangeiras estudadas e as fontes de direito brasileiras, construir um modelo jurídico para regular as gestações de substituição no Brasil. O modelo normativo sugerido engloba a necessidade de verificação da real autonomia privada da mulher que irá gestar o embrião através de avaliação médica e psicológica, acompanhamento por advogado na elaboração do contrato em razão da natureza dos direitos envolvidos nesse tipo de negócio jurídico, e ainda homologação judicial do acordo, a serem realizados antes do início da execução do contrato. Essas regras foram extraídas da fusão dos modelos normativos dos EUA no sentido de encontrar uma melhor solução para a realidade brasileira. / The Contract Law has adjusted throughout history, being today inserted in an environment where faster technological evolution brings remarkable challenges for its interpreters. General clauses usually allow the definition of legal consequences to new situations and social facts. The general goal of this this thesis was to study the contract under actual and current reality, especially regarding the private autonomy in surrogate motherhood contracts, linked to constitutional principles, in the scope of the legal possibilities brought by the hermeneutic horizons of comparing the Law in Brazil and in the United States of America. The role of the interpreter has been more important establishing the scope and extension of the legal norm via interpretation, looking for the meaning of expressions such as “social function” in the Federal Constitution and through dialogue with other sources of Law interpretations. Under the phenomenological hermeneutic methodology applied to this thesis, it is possible to affirm that the interpreter has increased responsibilities attributing creative meaning to the general clauses existent in the regulatory texts. Recent technology developments have brought new challenges to the Law operators. In this new context, the lack of legal regulations in Brazil for cases of surrogate motherhood poses problematic situation for all parts: the surrogate pregnant, the intended parents and even the medical professionals. Due to the absence of legal framework to regulate the relations involved in such technique, the Federal Council of Medicine published a resolution restricting the rights of potential parts involved in such agreements. Nevertheless, such resolution cannot restrict constitutionally protected Fundamental Individual Rights, such as the right to liberty, which in this case can be interpreted as the right to elect to generate an embryo for another person. The hypothesis is a re-evaluation of the private autonomy of involded parts in agreements of surrogate motherhood, protecting the human dignity in these contractual relations, as well as the fundamental principles of the Law, aligning the Constitutional System and the International Huma Rights System, related to the subject, in the landscape of combined horizons of National Law and Foreign Law. Concerning the Brazilian Contract Law, the closest “contractual model” for a surrogate motherhood is the “rendering services contracts”, however it is important to mention that some peculiarities must be considered due to the specific type of services being rendered. Because of this, the actual private autonomy of the future pregnant must be evaluated, since there are Personality Rights also involved in such legal agreement. As a rule, in Brazil, Personality Rights cannot be relinquished. However, in some existing cases, this rule can be relativized, which demonstrates that such agreements can be licit, even those involving payments to the pregnant, as long as the parts private autonomy have been clearly established. To develop a normative model for surrogate motherhood to be used in Brazil, a research was conducted in three states of the United States of America. The objective is to help to build a legal framework for surrogate motherhood in Brazil based on both foreign and Brazilian sources of law. The suggested legal framework prescribes that the actual private autonomy of the woman to become pregnant must be verified through the following: medical and psychological evaluation; legal advice on the contract wording due to the nature of involved right; and court homologation of the agreement, prior to its execution. Such framework is derived from a combination of norms in the United States of America, properly adjusted to better fit the local realities in Brazil.

Because blades in jet engine compressors are subject to dynamic loads based on the engine's speed, it is essential that the blades are properly "tuned" to avoid resonance at those frequencies to ensure safe operation of the engine. The tuning process can be time consuming for designers because there are many parameters controlling the geometry of the blade and, therefore, its resonance frequencies. Humans cannot easily optimize design spaces consisting of multiple variables, but optimization algorithms can effectively optimize a design space with any number of design variables. Automated blade tuning can reduce design time while increasing the fidelity and robustness of the design. Using surrogate modeling techniques and gradient-free optimization algorithms, this thesis presents a method for automating the tuning process of an airfoil. Surrogate models are generated to relate airfoil geometry to the modal frequencies of the airfoil. These surrogates enable rapid exploration of the entire design space. The optimization algorithm uses a novel objective function that accounts for the contribution of every mode's value at a specific operating speed on a Campbell diagram. When the optimization converges on a solution, the new blade parameters are output to the designer for review. This optimization guarantees a feasible solution for tuning of a blade. With 21 geometric parameters controlling the shape of the blade, the geometry for an optimally tuned blade can be determined within 20 minutes.

Cette thèse présente un framework d’optimisation pour la conception hydrodynamique de forme d’hydrofoils. L’optimisation d’hydrofoil par simulation implique des objectifs d’optimisation divergents et impose des compromis contraignants en raison du coût des simulations numériques et des budgets limités généralement alloués à la conception des navires. Le framework fait appel à l’échantillonnage séquentiel et aux modèles de substitution. Un modèle prédictif est construit en utilisant la Régression par Processus Gaussien (RPG) à partir des données issues de simulations fluides effectuées sur différentes géométries d’hydrofoils. Le modèle est ensuite combiné à d’autres critères dans une fonction d’acquisition qui est évaluée sur l’espace de conception afin de définir une nouvelle géométrie qui est testée et dont les paramètres et la réponse sont ajoutés au jeu de données, améliorant ainsi le modèle. Une nouvelle fonction d’acquisition a été développée, basée sur la variance RPG et la validation croisée des données. Un modeleur géométrique a également été développé afin de créer automatiquement les géométries d’hydrofoil a partir des paramètres déterminés par l’optimiseur. Pour compléter la boucle d’optimisation,FINE/Marine, un solveur fluide RANS, a été intégré dans le framework pour exécuter les simulations fluides. Les capacités d’optimisation ont été testées sur des cas tests analytiques montrant que la nouvelle fonction d’acquisition offre plus de robustesse que d’autres fonctions d’acquisition existantes. L’ensemble du framework a ensuite été testé sur des optimisations de sections 2Dd’hydrofoil ainsi que d’hydrofoil 3D avec surface libre. Dans les deux cas, le processus d’optimisation fonctionne, permettant d’optimiser les géométries d’hydrofoils et confirmant les performances obtenues sur les cas test analytiques. Les optima semblent cependant être assez sensibles aux conditions opérationnelles. / This thesis presents a practical hydrodynamic optimization framework for hydrofoil shape design. Automated simulation based optimization of hydrofoil is a challenging process. It may involve conflicting optimization objectives, but also impose a trade-off between the cost of numerical simulations and the limited budgets available for ship design. The optimization frameworkis based on sequential sampling and surrogate modeling. Gaussian Process Regression (GPR) is used to build a predictive model based on data issued from fluid simulations of selected hydrofoil geometries. The GPR model is then combined with other criteria into an acquisition function that isevaluated over the design space, to define new querypoints that are added to the data set in order to improve the model. A custom acquisition function is developed, based on GPR variance and cross validation of the data.A hydrofoil geometric modeler is also developed to automatically create the hydrofoil shapes based on the parameters determined by the optimizer. To complete the optimization loop, FINE/Marine, a RANS flow solver, is embedded into the framework to perform the fluid simulations. Optimization capabilities are tested on analytical test cases. The results show that the custom function is more robust than other existing acquisition functions when tested on difficult functions. The entire optimization framework is then tested on 2D hydrofoil sections and 3D hydrofoil optimization cases with free surface. In both cases, the optimization process performs well, resulting in optimized hydrofoil shapes and confirming the results obtained from the analytical test cases. However, the optimum is shown to be sensitive to operating conditions.