Dissertations / Theses on the topic 'NAHS'

'L'obésité est actuellement un des enjeux majeurs de santé publique au niveau mondial et national. La NAFLD (non-alcoholic fatty liver disease) représente une des complications majeures associées à l'obesité et est considérée comme la manifestation hépatique du syndrome métabolique. Le terme NAFLD regroupe l'ensemble des lésions hépatiques évoluant de la stéatose isolée (réversible) vers l'hépatite stéatosique (NASH) ayant un potentiel de progression vers la fibrose, la cirrhose et éventuellement le carcinome hépatocellulaire. A l'heure actuelle, les mécanismes responsables de l'instauration chez le patient obèse d'une NAFLD, et surtout d'une NASH, ne sont pas élucidés. L'objectif de ma thèse était de déterminer chez des patients obèses si des altérations hépatiques du métabolisme lipidique et/ou de la fonction mitochondriale, dans un contexte de surcharge lipidique du foie, peuvent participer à l'évolution de la NAFLD. Des biopsies hépatiques chirurgicales peropératoires ont été obtenues de patients obèses morbides opérés d'une chirurgie bariatrique, ainsi que de témoins non obèses. Les flux métaboliques d'acide gras à chaîne longue (AGCL) réalisés à l'aide de l'oléate [1-¹⁴C] et l'exploration de la respiration mitochondriale ont été réalisés sur du tissu frais. Les résultats montrent une altération de la β-oxydation mitochondriale complète des AGCL chez les patients obèses ayant une NASH (réduction de ¹⁴c—CO₂, augmentation des ¹⁴ccorps acido-solubles, et baisse de la cétogenèse hépatique). La production de CO₂ (oxydation complète des AGCL) est corrélée négativement avec les contenus hépatiques en triglycérides et diacylglycérols, qui sont augmentés chez les patients obèses NASH par rapport aux autres groupes. La respiration mitochondriale a été mesurée par oxygraphie en présence de différents substrats et inhibiteurs mitochondriaux sur l'homogénat de foie ainsi que sur des mitochondries isolées. Une réduction générale de la respiration a été observée entre les sujets témoins et tous les groupes de patients obèses. Cependant, la NASH est associée à une diminution significative de la respiration mitochondriale par rapport aux autres patients obèses. Ces altérations ne sont pas associées à une modification de la masse mitochondriale, ni à une altération de l'expression protéique des complexes OXPHOS de la chaîne respiratoire
Obesity is currently one of the major public health issues worldwide and nationally. NAFLD (non-alcoholic fatty liver disease) represents one of the major complications associated with obesity, and is considered as the hepatic manifestation of metabolic syndrome. The term NAFLD extends from simple steatosis (reversible) to steatohepatitis (NASH) having potential progression to fibrosis, cirrhosis and possibly hepatocellular carcinoma. At present, the mechanisms responsible for the establishment of NAFLD in obese patients, and its evolution towards NASH, are not well understood. The aim of my thesis was to determine if alterations in liver lipid metabolism and/or mitochondrial function, in a context of fat overload of the liver, could participate in the development of NASH. Intraoperative surgical liver biopsies were obtained from morbidly obese patients undergoing bariatric surgery, as well as non-obese controls. The long-chain fatty acid (LCFA) metabolic fluxes using [1-¹⁴C]oleate and exploration of mitochondrial respiration were performed on fresh liver tissue. The results show impaired complete LCFA oxidation in obese NASH patients (decreased ¹⁴cCO₂increased ¹⁴c acido-soluble products, decreased ketogenesis). Hepatic ¹⁴cCO₂ production negatively correlates with liver triglyceride and diacylglycerol contents, which are increased in obese NASH patients compared to other groups. Mitochondrial respiration was measured by oxygraphy using different substrates and inhibitors in liver homogenate as well as isolated mitochondria. A general reduction in mitochondrial respiration was observed between control group and all obese patients groups. However, NASH is associated with a significant decreased mitochondrial respiratiorewhen compared to other obese patients. These alterations are not associated with a change in mitochondrial mass, nor in protein expression of respiratory OXPHOS complexes

Fundação Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro
A avaliação da qualidade de vida tem sido cada vez mais utilizada pelos profissionais da área de saúde para mensurar o impacto de doenças na vida dos pacientes, bem como para avaliar os resultados dos tratamentos realizados. O crescente interesse por protocolos de pesquisa clínica em doenças não degenerativas do quadril tem encontrado muitos obstáculos na avaliação objetiva de seus resultados, principalmente nos estudos de observação de novas intervenções terapêuticas, como a artroscopia. O Nonarthritic Hip Score (NAHS) é um instrumento de avaliação clínica, desenvolvido originalmente em inglês, cujo objetivo é avaliar a função da articulação do quadril em pacientes jovens e fisicamente ativos. O objetivo desse estudo foi traduzir esse instrumento para a língua portuguesa, adaptá-lo para a cultura brasileira e validá-lo para que possa ser utilizado na avaliação de qualidade de vida de pacientes brasileiros com dor no quadril, sem doença degenerativa. A metodologia utilizada é a sugerida por Guillemin et al. (1993) e revisado por Beaton et al. (2000), que propuseram um conjunto de instruções padronizadas para adaptação cultural de instrumentos de qualidade de vida, incluindo cinco etapas: tradução, tradução de volta, revisão pelo comitê, pré-teste e teste, com reavaliação dos pesos dos escores, se relevante. A versão de consenso foi aplicada em 30 indivíduos. As questões sobre atividades esportivas e tarefas domésticas foram modificadas, para melhor adaptação à cultura brasileira. A versão brasileira do Nonarthritic Hip Score (NAHS-Brasil) foi respondida por 64 pacientes com dor no quadril, a fim de avaliar as propriedades de medida do instrumento: reprodutibilidade, consistência interna e validade. A reprodutibilidade foi 0,9, mostrando uma forte correlação; a consistência interna mostrou correlação entre 0,8 e 0,9, considerada boa e excelente; a validade foi considerada respectivamente boa e excelente; a correlação entre NAHS-Brasil e WOMAC foi 0,9; e a correlação entre o NAHS-Brasil e Questionário Algofuncional de Lequesne foi 0,79. O Nonarthritic Hip Score foi traduzido para a língua portuguesa e adaptado à cultura brasileira, de acordo com o conjunto de instruções padronizadas para adaptação cultural de instrumentos de qualidade de vida. Sua reprodutibilidade, consistência interna e validade foram também demonstradas.
The assessment of quality of life has been increasingly used by health professionals to measure the consequences of disease on patients' lives and evaluate the results of treatments. The growing interest in clinical research protocols of non-arthritic hip diseases has found many difficulties in dealing with the objective assessment of its results, especially in observational studies of new therapeutic interventions such as arthroscopy. The Nonarthritic Hip Score (NAHS) is a clinical assessment tool, originally developed in English to evaluate the function of the hip joint in young and physically active patients. The aim of this study was to translate this instrument into Portuguese, adapt it to the Brazilian culture and validate it, in order to evaluate quality of life of Brazilian patients with hip pain without osteoarthritis. The methodology used is suggested by Guillemin et al., (1993) and reviewed by Beaton et al., (2000), who proposed a set of standardized instructions for cultural adaptation of instruments for quality of life, including five steps: translation, back translation, review by committee, pre-test and test with a reassessment of the weights of scores, if relevant. The consensus version was administered to 30 individuals. Questions about sports and household chores were modified to better adapt to the Brazilian culture. The Brazilian version of Nonarthritic Hip Score (NAHS-Brasil) was answered by 64 patients with hip pain to evaluate the measurement properties of the instrument: reproducibility, internal consistency and validity. Reproducibility was 0.9, showing a strong correlation; the internal consistency showed a correlation between 0,8 and 0,9, considered good and excellent; the validity was considered good and excellent respectively; the correlation between NAHS-Brasil and WOMAC was 0,9, and the correlation between NAHS-Brasil and Lequesne Algofunctional Index was 0.79. The Nonarthritic Hip Score was translated into Portuguese and adapted to Brazilian culture, according to the instruction set of standardized instruments for cultural adaptation of quality of life. Its reliability, internal consistency and validity have also been demonstrated.

Scant research exists investigating the relationship between antecedent life experiences and the development of transformational leadership behaviors. The purpose of this research was to investigate the relationship between education leaders' life experiences and their effectiveness as transformational leaders. To guide this study, two research questions were formulated: (1) Does a relationship exist between perceived transformational leadership skills and the lifespan factors of K-12 principals? (2) Which lifespan factors investigated for this study have the most influence on perceived transformational leadership skills?

The intent of my thesis is to find a way to integrate a large big-box retailer into a community in such a way that it benefits the community as a whole. This must be accomplished within the parameters that mark the store as a viable option for the parent company as well. This ideal must be approached from the philosophy that box stores are a large part of the current American way of life and to let them grow unchecked will signal the inevitable death of downtown retail districts as more and more business gets sucked to the super-stores and the areas immediately surrounding them. To do this we will need to find what benefits a box-store can add to a community and further research and rethink the typically negative aspects of these retail giants to find a way to incorporate them into our downtown shopping districts, without destroying their original feel. With this thesis, it is my intent to create a viable model that allows box stores to act as anchors and catalysts for a downtown area (either existing or built) rather than its death knell. To do this I will be rethinking a number of design strategies with the seamless integration of community and big-box retail in mind. To this end, I will not be acting to simply find a way to add a box-store and its typical trappings to the end of historic downtown street, but rather to find away to integrate a set of large box stores into a downtown community in such a way that benefits the citizens of that community on every designable level. I will be challenging not only the typical design strategies of a box store, but those of a typical downtown community as well. Seven major design strategies will be looked at during this project, they are: 1. Design for a diversity of use and users 2. Design a safe and secure streetscape that will encourage use. 3. Design a streetscape that accommodates pedestrians as equals with vehicle traffic. 4. Design a destination, not just a path. 5. Design it well. 6. Balance supply with demand. 7. Use aesthetics as an integration tool. With these design strategies, a box store can become an integral part of a downtown community ... or at least a much better alternative to the rampant sprawl that occurs with their current implementation strategy.

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
O presente trabalho tem por objetivo abordar aspectos fundamentais da teoria de imersão proposta por John Nash em 1954, na qual foi mostrado que uma variedade continua com derivada continuação nua C1, pode ser imersa em espaços euclidianos de 2n dimensões. Faz-se importante citar que ao longo do trabalho serão destacados aspectos inovadores do Teorema de Nash, tais como a não necessidade da hipótese de analitici-dade conforme havia sido usada anteriormente por Janet-Cartan, além do aspecto da perturbação que permite construir qualquer outra variedade imersa por uma sequência de deformações infinitesimais. São discutidos também extensões do Teorema de Nash, sobretudo os trabalhos de Greene e de Gunther, e aplicações do método perturbativo de Nash nas Teorias unificadoras da física.
The present work has for objective to approach basic aspects of the immersion theory proposal for John Nash in 1954, in which it was shown that a continuous variety with continuous derivative C1, can be immersed in Euclidean spaces of 2n dimensions. One becomes important to cite that throughout the work innovative aspects of the The- orem of Nash will be detached, such as the necessity of the hypothesis of in agreement analiticidade had not been used previously for Janet-Cartan, beyond the aspect of the disturbance that allows to construct any another immersed variety for a sequência of infinitesimal deformations. Extensions of the Theorem of Nash are also argued, over all the works of Greene and Gunther, and applications of the perturbativo method of Nash in the unifying Theories of the physics.

Many pollutants are released to the environment due the use of petroleum and its derivatives. Some of them are classified as Polycyclic Aromatic Hydrocarbons (PAHs). Most of PAHs, or their metabolites, can interact with nitrogenous bases or cause lesions in DNA, potentiating mutations and consequently inducing the development of cancer. As a result of this, in the last decades, the concerns about contamination of soil and groundwater by PAHs have substantially increased. Various microorganisms have the capacity to use these hazardous molecules as carbon and energy source. The use of these microorganisms and/or their enzymes for the elimination of PAHs to the environment is a potential strategy for bioremediation. One of the most common and hazardous PAH is naphthalene, and because of the bacteria Pseudomonas putida ability to completely degrade it, it has been the focus of numerous studies. This work was focused in the study of two enzymes from P. putida involved in naphthalene degradation: NahE (a hydratase-aldolase) and NahK (a decarboxylase). The main objectives of this work were the amplification and cloning of nahE and nahK genes, expression and purification of NahE and NahK enzymes for biochemical and structural assays. The genes were initially cloned into the expression vector pET28a-TEV and expressed in Escherichia coli. The recombinant protein NahE was mainly detected in insoluble fraction and different trials were performed to obtain the protein in the soluble fraction, without success. Soluble NahE was obtained only when using denaturizing conditions of purification followed by a refolding protocol. On the other hand, NahK was detected in the soluble fraction and was purified by affinity and size-exclusion chromatographies. The purified proteins were submitted to Dynamic Light Scattering and Circular Dichroism experiments. Crystallization assays were also performed with NahK aiming crystal growth for elucidation of its three-dimensional structure by X-Ray Crystallography.
Devido ao uso do petróleo e seus derivados, diversos tipos de poluentes são liberados no meio ambiente. Alguns deles são classificados como Hidrocarbonetos Aromáticos Policíclicos (HAPs). A maioria dos HAPs, ou seus metabólitos, são capazes de interagir com bases nitrogenadas causando lesões no DNA, potencializando mutações e, consequentemente, o desenvolvimento de câncer. Como resultado disso, houve nas últimas décadas um aumento substancial na atenção dada às contaminações de solos e lençóis freáticos por HAPs. Inúmeros microrganismos possuem a capacidade de utilizar essas moléculas tóxicas como fontes de carbono e energia. O uso de determinadas bactérias (ou de suas enzimas) através de técnicas de biorremediação é uma estratégia em potencial para eliminação dos HAPs do ambiente. O HAP mais comum e tóxico é o naftaleno, e graças à capacidade da bactéria Pseudomonas putida em degradá-lo completamente, ela tem sido o foco de inúmeras pesquisas. Neste trabalho foram estudadas duas enzimas de P. putida envolvidas na degradação de naftaleno: NahE (uma hidratase-aldolase) e NahK (uma decarboxilase). O objetivo principal do trabalho foi a amplificação e clonagem dos genes nahE e nahK, expressão e purificação das respectivas enzimas para ensaios bioquímicos e estruturais. Os genes foram clonados inicialmente no vetor de expressão pET28a-TEV e expressos em Escherichia coli. A proteína recombinante NahE foi detectada em fração insolúvel e diversas estratégias foram utilizadas, sem sucesso, para obtenção da proteína expressa em fração solúvel. NahE solúvel foi obtida utilizando purificação em condições desnaturantes seguida por reenovelamento. Por outro lado, a proteína recombinante NahK foi detectada em fração solúvel e purificada por cromatografias de afinidade e de exclusão molecular. As proteínas purificadas foram submetidas a ensaios de Espalhamento Dinâmico de Luz e Dicroísmo Circular. Também foram realizados ensaios de cristalização com NahK visando o crescimento de cristais para a elucidação de sua estrutura tridimensional por cristalografia de Raios-X.

Message-oriented middleware (MOM) is a middleware used for communication between applications. There are many different MOM technologies available today, each offering different performance (throughput and latency). The performance of MOMs depends on both message size and message guarantee settings used. The problem is that it can be difficult for users to know which MOM they should choose given their requirements. The goal was to create a performance (latency and throughput) comparison of three popular MOMs; Apache Kafka, RabbitMQ and Nats Streaming. The result shows that Kafka is the best performing MOM for smaller message sizes (under 512 bytes). RabbitMQ has the best performance for larger message sizes (over 32768 bytes). Nats Streaming only outperformed the other message system for a few combinations of message guarantee settings with the message size 4096 bytes.
Meddelandeorienterad mellanprogramvara (MOM) är mellanprogramvara som används för kommunikation mellan applikationer. Det finns många MOM system som erbjuder olika prestanda (genomströmning och latens). Prestandan är beroende av vilka meddelandegarantier som används samt meddelande storlek. Detta gör det svårt för användare att välja MOM utifrån sina krav. Målet är därför att jämföra tre populära MOMs; Apache Kafka, RabbitMQ och Nats Streaming. Resultaten visar att Kafka presterar bäst med små meddelandestorlekar (Under 512 bytes). RabbitMQ presterar bäst för större meddelanden (Över 32768 bytes) medans Nats Streaming enbart presterar bäst med ett begränsat antal meddelandegarantier och med en meddelandestorlek på 4096 bytes.

Uncoordinated frequency hopping (UFH) has recently emerged as an effective mechanism to defend against jamming attacks. Existing research focuses on the optimal design of the hopping pattern, which implicitly assumes that the strategy of the attacker is fixed. In practice, the attacker might adjust its strategy to maximize its damage on the communication system. In this thesis, we study the design of optimal hopping pattern (the defense strategy) as long as the optimal jamming pattern (the attack strategy). In particular, we model the dynamic between the legitimate users and the attacker as a zero sum game, and study the property of this game. We show that when the legitimate users and the jammer can access only one channel at any time, the game has a unique Nash equilibrium. In the Nash equilibrium, the legitimate users and Eve will access or jam only a subset of channels that have good channel quality. Furthermore, the better the channel, the larger the probability that Eve will jam the channel and the smaller the probability the legitimate users will access this channel. We further extend the study to multiple access multiple jamming case and characterize the Nash equilibrium. We also give numerical results to illustrate the analytical results derived in this thesis.

Dans la première partie de la thèse on étudie un algorithme combinatoire qui correspond à l'itération de la modification de Nash d'une variété torique. On montre que, dans le cas de la dimension deux, cet algorithme s'arrête pour certains choix de cartes affines de la modification de Nash. De plus, on donne une borne pour le nombre d'itérations nécessaire pour que l'algorithme s'arrête dans les cas que l'on considère. Soit C(x_1,x_2) le corps des fonctions d'une surface torique. Alors notre résultat implique que pour toute valuation v centrée sur la surface torique tel que v(x_1) n'est pas un multiple irrationnel de v(x_2), une itération finie de la modification de Nash donne une uniformisation locale le long de cette valuation. Dans la deuxième partie on étudie la notion d'éclatement de Nash supérieur d'une variété algébrique. Cette notion consiste à remplacer des points singuliers par des limites de certains espaces vectoriels associés aux points non singuliers de la variété. On donne une description combinatoire de l'éclatement de Nash supérieur dans le cas de variétés toriques normales. En utilisant cette description, on montre que l'analogue du théorème de Nobile sur l'éclatement de Nash usuel est aussi valide dans ce contexte. Plus précisément, on montre que pour une variété torique normale, l'éclatement de Nash supérieur est un isomorphisme si et seulement si la variété est non singulière
In the first part of the thesis we explore a combinatorial algorithm that corresponds to the iteration of Nash modification on not necessarily normal toric varieties. We show that for toric surfaces this algorithm stops for certain choices of affine charts of the Nash modification. In addition, we give a bound on the number of steps required for the algorithm to stop in the cases we consider. Let C(x_1,x_2) be the field of rational functions of a toric surface. Then our result implies that for any valuation v centered on the toric surface such that v(x_1) is not an irrational multiple of v(x_2), a finite iteration of Nash modification gives local uniformization along this valuation. In the second part of the thesis we explore the notion of higher Nash blowup of an algebraic variety which is a modification that replaces singular points with limits of certain spaces carrying higher order data associated to the variety at non-singular points. In the case of normal toric varieties we give a combinatorial description of the higher Nash blowup in terms of a Groebner fan. This description allow us to prove the analogous of Nobile's theorem on the usual Nash blowup in this context. More precisely, we prove that for a normal toric variety, the higher Nash blowup is an isomorphism if and only if the variety is non-singular

Un cadre d'optimisation multi-Objectif pour les pales d'hélicoptère est développé en utilisant des modèles de simulation de haute fidélité. Des fonctions objectives caractérisant la performance de l'hélicoptère en vol stationnaire et d'avancement sont retenues. Deux solveurs sont utilisés afin de prédire la performance du rotor: le code général HOST et le solveur CFD elsA. Le premier axe de recherche porte sur la caractérisation de la précision des méthodes de prédiction. L'influence de la prise en compte de la souplesse de la pale, du trim rotor et/ou de l'utilisation de modélisations aérodynamiques simplifiées est caractérisée pour chaque cas de vol en utilisant des mesures en soufflerie. Un cadre numérique adapté à l'optimisation est développé. Le deuxième axe de recherche porte sur des techniques d'optimisation multi-Objectif de pales en vol stationnaire et d'avancement. Deux algorithmes novateurs basés sur la compétition (Jeux de Nash) et la coopération (Descente à Gradients Multiples) sont présentés comme des alternatives aux approches traditionnelles pour traiter le problème multi-Objectif. Afin de réduire le coût des simulations, un cadre de simulation basé sur des métamodèles est développé y compris une stratégie multi-Fidélité pour prédire la performance du rotor en vol d'avancement. Ces techniques sont appliquées à un cas réaliste de rotor, en utilisant des simulations CFD trimmées avec pale souple pour le cas du vol d'avancement et des simulations CFD avec pale rigide en vol stationnaire. Les résultats sont ensuite analysés, démontrant le potentiel de ces techniques pour l'obtention de conceptions réalistes représentant des bons compromis entre les objectifs
This work addresses the development of a multi-Objective optimization framework for helicopter rotor blades using high-Fidelity simulation models. In particular, objective functions corresponding to hover and forward flight are considered. Two solvers are used to predict the rotor performance: the comprehensive rotor code HOST and the Computational Fluid Dynamics (CFD) solver elsA. The first research axis of this work is the characterization of the accuracy of each available prediction method. The influence of considering the blade elasticity, the rotor trim and/or simplified aerodynamics is characterized for each flight case using wind-Tunnel data. As a result, a numerical framework adapted to the optimization is developed. The second part of this work concerns the formulation and development of techniques adapted to the multi-Objective optimization of rotor blades in hover and in forward flight. Innovative algorithms based on competition (Nash Games) and cooperation (Multi-Gradient Descent) are presented as alternatives to traditional multi-Objective approaches. In order to reduce the simulation costs, a surrogate-Based framework is developed, including a multi-Fidelity strategy to predict the rotor performance in forward flight. These techniques are finally applied to a realistic rotor, considering trimmed elastic CFD computations in the forward flight case and rigid blade CFD computations in the hover case. The results are subsequently analyzed, demonstrating the potential of these techniques to obtain realistic designs realizing interesting trade-Offs

Ce travail étudie certains problèmes liés à la caractérisation du comportement rationnel dans les interactions stratégiques d'oligopole. La première partie traite de l'impact de la renégociation sur la robustesse des équilibres de Nash parfaits. Nous passons en revue les principaux résultats de la littérature sur ce sujet et nous examinons les conséquences de la renégociation sur les possibilités de collusion dans la répétition d'un oligopole de Cournot. Dans une deuxième partie, nous présentons le concept d'un ensemble stable suggéré par Kohlberg et Mertens, nous utilisons ce concept pour résoudre complètement un jeu de duopole à deux étapes et nous le confrontons a d'autres raffinements récents de l'équilibre de Nash
This work studies some problems related to the caracterization of the rational behaviour in oligopoly strategic interactions. The first part deals with the impact of renegotiation on the consistency of subgame perfect equilibria. We review the main results in the literture about this subject and we examine the possibilities of collusion in finite horizon repeated oligopoly games when players are able to renegociate their actions. In the second part we present the stable set concept suggested by Kohlberg and Mertens. We make use of it in the solution of a two step duopoly game and we compare this concept to other recent refinements of Nash equilibrium

Ce travail se concentre sur l'étude de jeux joués sur des graphes finis, parun nombre arbitraire de joueurs, dont les objectifs ne sont pas antagonistes.Chaque joueur représente un agent, c'est-à-dire un programme, un processus,ou un périphérique, qui interagit avec les autres joueurs et leurenvironnement commun dans le but de satisfaire au mieux son objectifindividuel.Des concepts telsque les équilibres de Nash, permettant d'exprimer l'optimalité des stratégiesdes joueurs, ont été étudiés dans un cadre déterministe, et l'existencede tels équilibres n'est pas assurée, même lorsque les objectifs des joueurssont de simples conditions d'accessibilité ou de sûreté. En effet, lorsqueles joueurs jouent de manière déterministe, le système évolue en conservantune certaine symmétrie, ce qui nous motive à considérer un modèle stochastiqueoù les joueurs et l'environnement sont sources d'aléa. Dans le premier cas,nous montrons que les concepts classiques d'équilibres de Nash ne peuventêtre calculés, et introduisons des notions approchées d'équilibrescalculables. Dans le deuxième cas, nous nous intéressons à l'analyse desystèmes composés d'un nombre arbitraires de processus, dont l'éxécutionest déterminée par un ordonnanceur, c'est-à-dire l'environnement,probabiliste
We study games played on graphs by an arbitrary number of players withnon-zero sum objectives. The players representagents (programs, processes or devices) that can interact to achieve their ownobjectives as much as possible. Solution concepts, as Nash Equilibrium, forsuch optimal plays,need not exist when restricting topure deterministic strategies, even with simple reachability or safetyobjectives. The symmetry induced by deterministic behavioursmotivates the studies where eitherthe players or the environment can use randomization. In the first case, weshow that classical concepts are undecidable with a fixednumber of agents and propose computable approximations.In the second case, we studyrandomization as a reasonable policy for scheduling an arbitrary number ofprocesses

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Copy Number Variation (CNV) has been associated with intelectual disability (ID) and this condition occur in approximately 2% of world population. Chromosomal Microarray Analysis (CMA) is being indicated as first-tier test for individuals with ID and has also helped to understand the mechanisms of CNV formation, classification of these rearrangements, type of recurrence, and its origin. The aim of this study was to infer the parental chromosome origin of de novo pathogenic CNV in patients with ID and their mechanisms of formation. Patients with clinical indications of ID were referred to Replicon Research Group/LaGene for G-band karyotyping. CMA approach was done for patients without numerical and/or structural rearrangements results in karyotype. After performing CMA and classification of CNVs, the parental origin of pathogenic CNVs was done using Mendelian error check based on SNPs markers available by ChAs software. In addition, the UCSC Genome Browser website was used to detect Low Copy Repeats (LCR) surrounding the CNVs to infer the mechanisms of their formation. In the period from 2013 to 2015 was performed G-band karyotyping in 290 patients with clinical indication of ID and a total of 193/290 (66.5%) were diagnosed by Karyotype. The group of patients who were not diagnosed using the karyotype, only 76/97 (78.3%) agreed to continue the investigation by CMA’s approach. After performing CMA, a total of 15 de novo pathogenic CNVs were observed, 10 CNV of loss and 5 CNV of gain, in 13/76 (17.1%) patients. The analysis of the parental origin showed 60% of CNVs are of maternal origin and 40% of paternal origin. It was not possible to detect the influence of parental age in the formation of CNVs. After analyzing the presence of surrounding LCRs, it was observed that 46.7% are recurrent CNVs and the mechanism of formation was Non- Allelic Homologous Recombination (NAHR), and 71.4% of these recurrent CNVs are of maternal origin. These data are in agreement with studies that affirm that the majority of CNVs of paternal origin are nonrecurrent due to germ cells replicate many times their genetic material in the pre-meiotic phase, being possible to infer the mechanism of formation of CNV that may have been by Microhomology-mediated break-induced replication (MMBIR) or Non-homologous end joining (NHEJ).
A variação no número de cópias (CNV) no genoma é um dos fatores etiológicos que pode desencadear a condição da deficiência intelectual (DI), sendo que esta condição atinge cerca de 2% da população mundial. A metodologia de análise cromossômica por microarranjo (CMA) além de ser indicada como teste de primeira escolha para pacientes com DI, tem ajudado também na compreensão da formação de CNVs e classificação destes rearranjos, quanto à patogenicidade, o tipo de recorrência e sua origem. E este estudo objetivou inferir a origem cromossômica parental das CNVs de novo patogênicas em pacientes com DI e seu mecanismo de formação. Os pacientes com indicação clínica de DI foram encaminhados ao Núcleo de Pesquisas Replicon/LaGene para realização do cariótipo com bandeamento GTG, e subsequentemente, os que não tiveram alteração numérica e/ou estrutural no cariótipo foram convidados a continuar a investigação em nível genômico, pela metodologia de CMA. Após realização do CMA e classificação das CNVs, foram realizadas a análise da origem parental das CNVs de novo patogênicas pela análise do erro mendeliano usando os marcadores de SNPs disponibilizado pelo software ChAS. Adicionalmente, foi usado o UCSC Genome Browser para detectar Repetições De Poucas Cópias (LCR) circundantes as CNVs para inferir o mecanismo de formação das mesmas. Foi realizado o cariótipo em 290 pacientes com indicação clínica de DI entre os anos de 2013 a 2015 e em 193/290 (66,5%) foram diagnosticados pelo cariótipo. Do conjunto de pacientes que não foram diagnosticados usando o cariótipo, apenas 76/97 (78,3%) aceitaram continuar a investigação pelo CMA. Após realizar o CMA, foi observado 15 CNVs de novo patogênicas, 10 CNVs de perda e 5 CNVs de ganho, em 13/76 (17,1%) pacientes. Na análise da origem parental, observou-se que 60% das CNVs são de origem materna e 40% de origem paterna. Não foi possível detectar a influência da idade parental na formação das CNVs. Ao analisar a presença de LCRs circundantes, observou-se que 46,7% das CNVs de novo patogênicas são recorrentes e o mecanismo de formação foi a Recombinação Homologa Não Alélica (NAHR), e 71,4% dessas CNVs recorrentes são de origem materna. Esses dados corroboram com os estudos que afirmam que a maioria das CNVs de origem paterna são não recorrentes devido às células germinativas replicarem inúmeras vezes o seu material genético na fase pré-meiótica, sendo possível inferir sobre o mecanismo de formação que pode ter sido por Replicação Induzida por Quebra e Mediada por Microhomologia (MMBIR) ou Junção de Extremidade Não Alélica (NHEJ).

Metallic nano-particles or nano-antennas (NAs) provide a strong spatial confinement down to the sub wavelength regime. However, a key challenge is to address and collect light from those nano-scale systems. The tiny active area of the NA is both an advantage for its miniaturization, and a real limit for the level of the collected signal. Therefore, one needs to reconsider how to drive efficiently such NA. Here, we propose to tackle this important issue by designing and realizing a novel nano-optical device based on the use of a photonic crystal cavity (PC cavity) to generate an efficient coupling between the external source and a NA. In this thesis, we design and realize a novel nano-optical device based on the coupling engineering of a photonic crystal (PC) cavity and a nanoantenna (NA). The research work includes nanodevice design, fabrication and characterization. The PC structures are formed in an InP-based membrane with four InAsP quantum wells are in the centre of the membrane to act as an optical gain material of laser mode. The PC structures include defect mode PC structures and Bloch mode PC structures. The bowtie NAs are placed on the backbone of the PC structures. The fabrication of the PC is done by electron beam lithography. Reactive ion beam etching (RIBE) is used to transmit the patterns of PC structures into the InP layer. The NAs are then deterministically positioned on the PC structures by a second e-beam exposure followed by a lift-off process. Overlay measurements showed that the deviation in the alignment error could be as small as 20nm.Optical properties of the hybrid structure are investigated in both far-field and near-field. The far-field measurement shows that the NA increases the lasing threshold of the PC cavity. The wavelength of the laser is also impacted. Near-field scanning optical microscopy (SNOM) has employed to investigate the near-field optical field distribution. The measurement results show that the NA modifies the mode of the structure and localizes the optical field under it. The modification depends on the position and orientation of the NA.

Nous nous intéressons à l'étude des singularités réelles à l'aide d'arguments provenant de l'intégration motivique. Une telle démarche a été initiée par S. Koike et A. Parusiński puis poursuivie par G. Fichou. Afin de donner une classification des singularités réelles, T.-C. Kuo a défini la notion d'équivalence blow-analytique. Il s'agit d'une relation d'équivalence pour les germes analytiques réels n'admettant pas de module continu pour les singularités isolées. Cette notion est étroitement liée à la notion d'applications analytiques par arcs définie par K. Kurdyka. Il est donc naturel d'adapter des arguments provenant de l'intégration motivique pour l'étude de l'équivalence blow-analytique. La difficulté réside désormais dans le fait de trouver des méthodes permettant de montrer que deux germes sont équivalents et de construire des invariants permettant de distinguer deux germes qui ne sont pas dans la même classe. Nous travaillons avec une variante plus algébrique de cette notion, l'équivalence blow-Nash introduite par G. Fichou. La première partie de la thèse consiste en un théorème d'inversion donnant des conditions pour que l'inverse d'un homéomorphisme blow-Nash soit encore blow-Nash. L'intérêt d'un tel énoncé est que de telles applications apparaissent dans la définition de l'équivalence blow-Nash. La seconde partie est consacrée à l'étude d'une nouvelle fonction zêta motivique. Il s'agit d'associer à un germe analytique une série formelle. Cette fonction zêta motivique généralise les fonctions zêta de Koike-Parusiński et de Fichou et admet une formule de convolution. Il s'agit d'un invariant pour l'équivalence blow-Nash
The main purpose of this thesis is to study real singularities using arguments from motivic integration as initiated by S. Koike and A. Parusiński and then continued by G. Fichou. In order to classify real singularities, T.-C. Kuo introduced the blow-analytic equivalence which is an equivalence relation on real analytic germs without moduli for isolated singularities. This notion is closely related to the notion of arc-analytic maps introduced by K. Kurdyka, thus it is natural to adapt arguments from motivic integration to the study of the relation. The difficulty lies in finding efficient ways to prove that two germs are equivalent and in constructing invariants that distinguish germs which are not in the same class. We focus on the blow-Nash equivalence, a more algebraic notion which was introduced by G. Fichou. The first part of this thesis consists in an inverse theorem for blow-Nash maps. Under certain assumptions, this ensures that the inverse of a homeomorphism which is blow-Nash is also blow-Nash. Such maps are involved in the definition of the blow-Nash equivalence. In the second part, we associate a power series to an analytic germ, called the zeta function of the germ. This construction generalizes the zeta functions of Koike-Parusiński and Fichou. Furthermore, it admits a convolution formula while being an invariant for the blow-Nash equivalence

O presente trabalho busca apresentar uma aplicação da teoria dos jogos, de modo a complementar a literatura que utiliza esse referencial teórico e alcançar conclusões pertinentes que desafiam o senso comum. O assunto trabalhado são os debates políticos televisivos e o excesso de acusações realizadas pelos participantes. Através de premissas e expectativas dos jogos não cooperativos, que foram aplicadas sobre os debates de 2º turno das eleições presidenciais de 1989, 2006, 2010 e 2014, a hipótese de que a razão de tal comportamento é a própria organização do jogo, e não uma eventual falta de propostas a serem apresentadas pelos políticos, não é refutada empiricamente. Além disso, sugestões de mudanças de regras desses programas são realizadas, de modo que seu objetivo principal, a exposição de planos de governo, passe a ser atingido.
The present work seeks to present an application of the Game Theory, in order to complement the literature that uses this theoretical reference and to reach pertinent conclusions that defy common sense. The topic that is going to be studied are the televised political debates and the excess of accusations made by the participants. Through assumptions and expectations of non-cooperative games, that were applied to the 2nd round debates of the 1989, 2006, 2010 and 2014 presidential elections, the hypothesis that the reason for such behavior is the organization of the game, not an eventual lack of proposals by the political parties, is not empirically refuted. In addition, suggestions for changes in the rules of these programs are made, in order to ensure that the primary debates\' goal of exposing government plans is reached.

O modelo a ser apresentado consiste em um jogo de preço e localização entre duas firmas. Utiliza-se o pressuposto de que os consumidores têm sua utilidade positivamente afetada por um efeito de rede, ou seja, são diretamente influenciados pela tamanho da demanda do bem. Dispondo os consumidores uniformemente distribuídos dentro de um intervalo linear [0, 1], buscamos encontrar os equilíbrios de preço e localização do jogo proposto. Verificamos que, dados os pressupostos do modelo, existem equilíbrios de Nash para cada subjogo e dependerão da força dos efeitos de rede. Quando os efeitos de rede são fortes o suficiente, os preços praticados serão inicialmente reduzidos até que o monopólio seja alcançado por uma das firmas, quando o preço será elevado e a outra firma passará a cobrar um preço nulo. No subjogo de localizações foi possível identificar que, no caso em que o poder do efeito de rede está acima de um determinado nível, as firmas não irão diferenciar seus produtos e se localizarão em algum ponto dentro do intervalo fechado [1/4 , 3/4]
The model to be presented is a price-location game between two firms. The assumption is that consumers\' utility is positively affected by a network effect, i.e. it is directly influenced by the size of demand. Distributing consumers uniformly in a linear interval [0, 1] we seek the price and location equilibrium of the proposed game. We found that, given the model assumptions, there are Nash equilibria for each subset that depend on the strength of network effects. When network effects are strong enough, prices are initially reduced until the monopoly is reached by one of the firms, then the price rises and the other firm shall charge a null price. In the subgame of locations, when the power of the network effect is above a certain level, the firms will not differentiate their products and will be located at any point within the closed interval [1/4 , 3/4]

O câncer é um dos principais problemas de saúde pública no mundo. Dentre as neoplasias primárias que acometem o fígado, o carcinoma hepatocelular (HCC) é a mais frequente. Diversos fatores de risco predispõem ao HCC, entre eles a doença hepática gordurosa não alcóolica (NAFLD). Segundo estudos prévios do grupo, a β-ionona (BI), apresenta potencial quimiopreventivo na hepatocarcinogênese, promovendo redução de lesões preneoplásicas (LPN). Assim pretendeu-se investigar se a NAFLD potencializaria o desenvolvimento de LPN em ratos Wistar submetidos ao modelo do hepatócito resistente (RH) na etapa de iniciação/promoção inicial da hepatocarcinogênese e se a BI apresenta efeito quimiopreventivo nesse contexto. Para tanto, os animais foram distribuídos em 4 grupos experimentais: grupo não-tratado (NT), grupo submetido ao RH (RH), grupo submetido ao RH e ao modelo de NAFLD, que consiste na administração de emulsão hiperlipídica, (AS) e grupo AS tratado com BI (AS + BI). Em uma primeira instância, 5 animais pertencentes aos grupos NT, AS,AS + BI foram eutanasiados após 6 semanas de administração de emulsão hiperlipídica, antes da aplicação do modelo RH, para se confirmar o desenvolvimento da NAFLD. Foi possível observar que a administração de emulsão hiperlipídica durante 6 semanas foi suficiente para o desenvolvimento de esteatose hepática. Após as 6 semanas foi introduzido o modelo do RH concomitante à administração da emulsão hipercalipídica até o fim do experimento na 13a semana . Após 13 semanas o grupo AS apresentou maiores (p<0,05) valores de focos de inflamação, hepatócitos balonizados e grau de esteatose hepática em relação ao grupo AS+BI, assim como maiores (p<0,05) níveis séricos de triacilgliceróis, colesterol, HDL, LDL, VLDL, e maior (p<0,05) valor de MDA em relação ao grupo RH embora sem diferença estatística. O grupo AS também apresentou maior (p<0,05) incidência, número total e multiplicidade de nódulos, além de maior (p<0,05) número e tamanho de LPN persistentes (pLPN) e índice de proliferação quando comparado aos grupos RH e AS+BI. O grupo AS + BI, por sua vez, demonstrou menores (p<0,05) valores de escore de células ovais e menores valores de comprimentos de cometa e danos no DNA quando comparado ao grupo AS, embora sem diferença estatista para este último parâmetro. Em relação à expressão gênica, o grupo AS apresentou menores (p<0,05) valores de expressão do gene Hmgcr em relação ao grupo RH e maiores (p<0,05) valores dos genes Insig 1 e Thy 1 quando comparados ao grupo AS+BI. Portanto, no contexto de esteatose hepática associada ao modelo do RH, a administração de BI durante a etapa de iniciação/promoção em ratos Wistar resultou em atividade quimiopreventiva que se deu pela diminuição de pLNP, redução da proliferação celular e do número de células ovais, consideradas potenciais alvos para o desenvolvimento da hepatocarcinogênese, entretanto os genes analisados parecem não serem modulados pela BI.
Cancer is a major public health problem in the world. Among the primary neoplasms affecting the liver, hepatocellular carcinoma (HCC) is the most frequent. Several risk factors predispose to HCC, including the nonalcoholic fatty liver disease (NAFLD). According to previous studies of the group, the β-ionone (BI), has potential chemopreventive in hepatocarcinogenesis, promoting reduction of preneoplastic lesions (LPN). Thus we investigated whether NAFLD would increase the development of LPN in Wistar rats resistant hepatocyte model (RH) at the stage of initiation / promotion of hepatocarcinogenesis and if BI has chemopreventive effect in this context. Therefore, the animals were divided into 4 groups: non-treated group (NT), the group submitted to HR (HR), the group submitted to HR and NAFLD model, consisting of the fatty emulsion administration (AS) and AS group treated with BI (AS + BI). In a first point, 5 animals belonging to the groups NT, AS, AS + BI were euthanized after 6 weeks of administration of fat emulsion prior to application of the HR model, to confirm the development of NAFLD. It was observed that the administration of fatty emulsion for 6 weeks was sufficient to the development of hepatic steatosis. After 6 weeks it was introduced into the model HR the concomitant administration of fatty emulsion until the end of the experiment at 13 weeks. In the endpoint, the AS group had higher (p <0.05) of serum triacylglycerols, cholesterol, HDL, LDL, VLDL although no statistical difference inrelation to RH group, and increased (p <0.05) amount of MDA in relation to the group RH. The AS group also had higher (p <0.05) incidence, multiplicity and total number of nodes and greater (p <0.05) number and size of persistent LPN (pLPN) and proliferation index when compared to HR groups and AS + BI. AS + BI group. It was observed in AS+BI group lower (p <0.05) cell oval score values compared to AS group. In addition the AS+BI group showed lower values of the comet length and DNA damage compared to the AS group, although no statistical differences. In relation to gene expression, the AS group showed lower(p <0.05) HMGCR gene expression values in relation to HR group and higher (p <0.05) expression of Insig genes 1 and Thy 1 compared to group AS + BI.Therefore, in the context of hepatic steatosis associated with HR model BI for administration to the stage of initiation / promotion in rats resulted in chemopreventive activity was due to decrease in area of pLNP, reducing cell proliferation, and the number of oval cells, as potential targets for the development of hepatocarcinogenesis, however the genes do not seem to be modulated analyzed by BI.

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A descoberta de significados autênticos é uma preocupação que está ligada à própria razão da vida. O fato de vivermos numa época regida pela lógica da 'otimização', da 'eficiência' e da um questionamento bandeiras. 'produtividade' organizacional merece dos símbolos que sustentam estas bandeiras.

Adefovir, an acyclic nucleotide reverse transcriptase inhibitor used to treat hepatitis B viral infection, is primarily eliminated renally through cooperation of glomerular filtration with active tubular transport. Nonalcoholic steatohepatitis is a variable in drug disposition, yet the impact on renal transport processes has yet to be fully understood. The goal of this study was to determine the effect of nonalcoholic steatohepatitis on the pharmacokinetics of adefovir in rats given a control or methionine and choline deficient diet to induce nonalcoholic steatohepatitis.

Orientador: Manoel Ferreira Borges Neto
Banca: Sandra Regina Monteiro Masalskiene
Banca: Antonio Luís Venezuela
Resumo: O presente trabalho tem por objetivo abordar aspectos fundamentais da teoria de imersão proposta por John Nash em 1954, na qual foi mostrado que uma variedade continua com derivada continuação nua C1, pode ser imersa em espaços euclidianos de 2n dimensões. Faz-se importante citar que ao longo do trabalho serão destacados aspectos inovadores do Teorema de Nash, tais como a não necessidade da hipótese de analitici-dade conforme havia sido usada anteriormente por Janet-Cartan, além do aspecto da perturbação que permite construir qualquer outra variedade imersa por uma sequência de deformações infinitesimais. São discutidos também extensões do Teorema de Nash, sobretudo os trabalhos de Greene e de Gunther, e aplicações do método perturbativo de Nash nas Teorias unificadoras da física.
Abstract: The present work has for objective to approach basic aspects of the immersion theory proposal for John Nash in 1954, in which it was shown that a continuous variety with continuous derivative C1, can be immersed in Euclidean spaces of 2n dimensions. One becomes important to cite that throughout the work innovative aspects of the The- orem of Nash will be detached, such as the necessity of the hypothesis of in agreement analiticidade had not been used previously for Janet-Cartan, beyond the aspect of the disturbance that allows to construct any another immersed variety for a sequência of infinitesimal deformations. Extensions of the Theorem of Nash are also argued, over all the works of Greene and Gunther, and applications of the perturbativo method of Nash in the unifying Theories of the physics.
Mestre

L’obésité est à l’origine de la première cause de maladies hépatiques dans les pays occidentaux. Les lésions hépatiques s’étendent de la stéatose isolée et réversible à la stéatohépatite (NASH), la fibrose, la cirrhose jusqu’au carcinome hépatocellulaire. Aucun traitement pharmacologique n’a montré son efficacité pour éviter cette évolution. La compréhension des mécanismes à l’origine du processus inflammatoire est donc un élément clef pour le développement de nouvelles voies thérapeutiques. Nous avons précédemment montré dans un modèle murin d’obésité que la stéatose induit un recrutement accru de lymphocytes par le foie. Les cellules de Kupffer représentent jusqu’à 20% des cellules immunitaires du foie. Elles peuvent présenter différents phénotypes : pro-inflammatoire ou anti-inflammatoire. Un phénotype pro-inflammatoire engendre la sécrétion de cytokines/chimiokines pro-inflammatoires favorisant une réponse immune de type Th1 et un recrutement de cellules immunitaires. Les cellules de Kupffer pourraient ainsi être des acteurs majeurs dans les étapes précoces du développement de la maladie.Le but de ce travail a été d’étudier le phénotype des cellules de Kupffer au stade de la stéatose et le rôle des lipides dans ce phénotype.Nous avons montré que l'accumulation de lipides dans les cellules de Kupffer est due à un dérèglement du métabolisme des lipides et de leur trafic. Les cellules de Kupffer chargées de lipides ont un phénotype pro-inflammatoire qui induit le recrutement des lymphocytes durant les premiers stades du développement de la NASH et qui est réversible par l'inhibition de la lipogenèse
We have shown lipid accumulation in fat-laden Kupffer cells is due to a dysregulation of lipid metabolism and trafficking. Fat-laden Kupffer cells are "primed" to recruit lymphocytes and exhibit a pro-inflammatory phenotype at the stage of steatosis, which is reversible with inhibition of lipogenesis

La sleeve gastrectomie (SG) est une opération qui consiste à réduire le volume de l’estomac. L’hypothèse que d’autres mécanismes indépendants de la perte de poids sont impliqués dans l’amélioration des complications métaboliques de l’obésité après SG a été émise. L’effet de la SG chez des souris soumis à un régime High Fat Diet a été étudié chez trois groupes d’animaux : SG, sham pair fed (SPF) et sham. Le test de tolérance au glucose montrait une amélioration de l’insulinorésistance des animaux SG à J23. Au niveau hépatique les animaux SG montraient une diminution significative de la stéatose. Il existe donc des mécanismes améliorant les complications hépatiques et métaboliques de l’obésité qui sont en partie indépendants de la réduction de l’apport calorique. Dans le second volet nous avons étudié l’évolution à long terme des lésions hépatiques liées à la NASH chez des patients obèses morbides avec une NASH lors de la chirurgie bariatrique. Dix patients d’une cohorte prospective ont été inclus. La deuxième biopsie a été réalisée à une médiane de 57 mois après le RYGB. La perte de poids moyenne était de –13,3 points de l’IMC lors du suivi. La rémission du syndrome métabolique et du diabète a été observée chez 71,6 % et 100 % des patients respectivement. Le NAS score a été amélioré chez tous les patients. Le taux sérique moyen du fragment clivé de la cytokératine 18 (M30), marqueur de l’apoptose hépatocytaire, était significativement abaissé. Le RYGB a permis une amélioration à long terme des lésions hépatocytaires liées à la NASH chez les patients obèses morbides. L’amélioration post-opératoire de la souffrance hépatocytaire corrèle avec la baisse du taux sérique du M30
The mechanisms responsible for weight loss and improvement of metabolic disturbances have not been completely elucidated. We investigated the effect of sleeve gastrectomy (SG) on body weight, adipose tissue depots, glucose tolerance, and liver steatosis independent of reduced caloric intake in high-fat-diet-induced obese mice. Mice fed a high fat diet were divided into 3 groups: SG, sham-operated ad libitum fed and sham-operated pair fed. SG mice showed improved glucose tolerance and lower levels of liver steatosis. This was associated with a decrease in the ratios of the weight of pancreas, epididymal and inguinal adipose tissues to body weight. Reduced white adipose tissue inflammation, modification of adipose tissue development, and ectopic fat are potential mechanisms that may account for the reduced caloric intake independent effects of SG. We also investigated long-term impact of RYGB surgery on liver complications in morbidly obese patients with NASH. Ten morbidly obese patients with biopsy-proven NASH were followed after RYGB and underwent a second liver biopsy. The median interval between the RYGB and second liver biopsy was 57 months. Clinical and biological data were obtained at baseline and ≥40 months after RYGB. RYGB was associated with significant weight loss, improved hepatic steatosis, resolution of hepatic inflammation and hepatocyte ballooning. Hepatocyte apoptosis, as evaluated by serum K18 fragment improved within the first year and at 57 months. Hepatic fibrosis resolved in 90% of cases. RYGB in morbidly obese patients with NASH is associated with a long-term beneficial impact on hepatic steatosis, inflammation, injury and, possibly, fibrosis

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro Sócio-Econômico.
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O orçamento empresarial é uma técnica de gestão que requer uma reorganização da realização das atividades na empresa, através do estabelecimento de objetivos que contemplem o resultado global da empresa, bem como um constante acompanhamento para aferir o programado com o realizado. Assim, este trabalho objetivou analisar a influência do planejamento, execução e controle do orçamento de despesas operacionais no desempenho dos gestores e no resultado de uma empresa comercial. A pesquisa é do tipo exploratória, tendo como método o estudo de caso, com cortes longitudinais, em caráter não experimental, e uma abordagem qualitativa. O nível de análise é organizacional e a empresa pesquisada está inserida no segmento do processo comercial. A população consistiu dos gerentes das unidades de negócios da Agrofel Comércio de Produtos Agrícolas Ferrarin Ltda., e o tipo de amostragem é intencional. Os dados foram coletados através de questionário com perguntas abertas e levantamento documental. O tratamento dos dados fez-se de forma descritiva. Observou-se pela análise dos dados que, após a implantação do orçamento de despesas operacionais, houve uma modificação significativa nos resultados operacionais da empresa. Quanto ao desempenho dos gestores, nos períodos analisados, verificou-se mudanças de comportamento no que concerne ao planejamento, execução e controle das atividades que estão sob sua responsabilidade. Destaca-se que agregou maior responsabilidade e comprometimento dos gestores para com sua equipe e a empresa como um todo.

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The thesis is that the conflict is the main cause of the postponement (by the government) of actions that could solve or mitigate the problems related to the occupation of water source regions in the Metropolitan Region of São Paulo. The overall objective of the research is to propose strategies to confront the conflict to the government and thus, open possibilities to contain the invasion and remove invaders from areas of springs. The specific objectives are (1) to present and analyze the strategies of the players (government and invader) based on the theory of Nash equilibrium and (2) to highlight the importance of game theory and in particular, Nash equilibrium as method to elaborate proposal conflict resolution according to selected strategies. The research methodology is qualitative and quantitative. The quantitative research is based on the data required for the use of game theory (urban spot growth, real estate prices, among others) and numerical simulations arranged in matrices. The qualitative, in the study of the literature on the problem of the occupation of springs that in turn, led to the design of possible strategies (for the solution of problems)
A tese sustentada neste trabalho é que o conflito é a principal causa do adiamento (por parte do governo) de ações que poderiam solucionar ou mitigar os problemas relativos à ocupação de regiões de mananciais na Região Metropolitana de São Paulo. O objetivo geral da pesquisa é propor estratégias de enfrentar o conflito para o governo e assim, abrir possibilidades de conter a invasão e remover invasores de áreas de mananciais. Os objetivos específicos são (1) apresentar e analisar as estratégias dos jogadores (governo e invasor) com base na teoria do Equilíbrio de Nash e (2) destacar a importância da teoria dos jogos e em particular do Equilíbrio de Nash como método para elaborar proposta de solução do conflito de acordo com estratégias selecionadas. A metodologia da pesquisa é qualitativa e quantitativa. A pesquisa quantitativa está no levantamento dos dados necessários à utilização da teoria dos jogos (crescimento da mancha urbana, preços dos imóveis, entre outros) e nas simulações numéricas dispostas em matrizes. A qualitativa, no estudo da literatura sobre o problema da ocupação de mananciais que por sua vez, levou ao desenho das estratégias possíveis (para a solução dos problemas). As simulações elaboradas a partir da teoria dos jogos mostraram que a melhor estratégia para a solução do conflito é que o governo remunere o invasor para preservar a região ocupada

A doença hepática gordurosa não alcoólica (DHGNA) é definida pelo acúmulo excessivo de gordura nos hepatócitos sem ingestão significativa de álcool. Essa condição é associada à obesidade e a síndrome metabólica (SM) e é considerada um grave problema de saúde pública global. A DHGNA engloba a esteatose pura e a esteatohepatite, esta última caracterizada pela presença de inflamação e balonização dos hepatócitos, com ou sem formação de fibrose com potencial para evolução para formas mais graves como cirrose e carcinoma hepatocelular. Estudos atuais divergem sobre a relação entre a deficiência da vitamina D e a gravidade da DHGNA. O objetivo foi verificar se há associação entre níveis séricos de vitamina D, citocinas relacionadas ao processo inflamatório (IL-6, IL-10 e TNF-?), presença de componentes da SM e a prevalência e a gravidade da DHGNA. Metodologia Estudo transversal que incluiu 40 pacientes do sexo feminino, obesas (IMC>30kg/m²) e com idade superior a 18 anos submetidas e biópsia hepática e obtiveram diagnostico de DHGNA. Foram coletados dados referentes a características clínicas, parâmetros antropométricos e de gordura corporal. Adicionalmente, foram avaliados parâmetros clínicos de SM e dados bioquímicos relacionados à lesão hepática além de dosagem de 25(OH)D e níveis séricos de citocinas. Um grupo controle com 37 indivíduos saudáveis do sexo feminino, não obesas (IMC<30kg/m²), com idade média de 41 anos, foi usado como controle de vitamina D sérica. Resultados Dos 40 pacientes incluídos, 25 tinham esteatose pura e 15 esteatohepatite. A prevalência de insuficiência de vitamina D foi de 70%. Os valores séricos de vitamina D não foram diferentes quando comparados ao grupo controle saudável e comparando-se esteatose e esteatohepatite. Níveis de vitamina D e de citocinas não apresentaram relação com os parâmetros histopatológicos de lesão hepática, exceto a presença de balonização que foi associada a maiores valores de vitamina D. Níveis séricos de vitamina D correlacionaram-se negativamente com o IMC. Níveis séricos de citocinas não foram associados com a gravidade da DHGNA. O escore NAS e o grau de balonização dos hepatócitos foram maiores em pacientes que apresentaram SM. Conclusões Apesar da alta prevalência de insuficiência de vitamina D, níveis séricos de vitamina D e citocinas não foram associados com presença ou gravidade da DHGNA em pacientes obesas do sexo feminino submetidas à cirurgia bariátrica. Balonização dos hepatócitos foi o único parâmetro histopatológico de gravidade de lesão hepática associado com níveis séricos mais altos de vitamina D. SM foi associada a parâmetros de maior gravidade de lesão hepática.
Nonalcoholic fatty liver disease (NAFLD) is defined by excessive fat accumulation in hepatocytes without significant alcohol intake and is associated with obesity and metabolic syndrome. NAFLD is one of the most common causes of chronic liver disease and it is considered a global public health problem. NAFLD includes pure steatosis and steatohepatitis; the last been characterized by the presence of inflammation and hepatocytes ballooning with or without fibrosis and with potential to evolve to more severe forms as cirrhosis and hepatocelular carcinoma. Current studies diverge on the relationship between vitamin D deficiency and the severity of NAFLD. The objective was to assess if there is an association between vitamin D serum levels, cytokines related to inflammation (IL-6, IL-10 and TNF-?) and presence of metabolic syndrome components and the prevalence and severity of NAFLD. Methods Cross-sectional study of 40 obese (BMI > 30kg/m²) female patients above 18 years who underwent hepatic biopsy during bariatric surgery to diagnose NAFLD and assess the degree of liver damage. Clinical data, anthropometric parameters and body fat were collected. In addition, clinical parameters of metabolic syndrome were evaluated and biochemical data relating to liver injury beyond 25(OH)D and serum cytokines. A control group with 37 healthy non obese females, mean age 41 was used as a controls for serum vitamin D. Results Among 40 NAFLD patients 25 had pure steatosis and 15 steatohepatitis. Prevalence of vitamin D insufficiency was 70%. No difference was observed in vitamin D levels comparing healthy control group and NAFLD or comparing steatosis and steatohepatitis. No relationship was observed between vitamin D or cytokine levels with histopathology parameters of liver injury. Higher levels of vitamin D were associated with cellular ballooning .Vitamin D levels negatively correlated with BMI. Serum cytokine levels were not associated with the severity of NAFLD. The NAS score and the ballooning degree were higher in patients with metabolic syndrome. Conclusions Despite high prevalence of vitamin D insufficiency, serum vitamin D and cytokines were not associated with the presence or severity of NAFLD in obese female patients undergoing bariatric surgery. Ballooning was the only histological parameter of liver damage associated with higher serum levels of vitamin D. Metabolic syndrome was associated with parameters of higher severity of NAFLD.

Napping has been explored extensively as a means of counteracting the negative effects associated with shift work. A significant amount of this research has focused on the implementation of scheduled naps, with few studies considering flexible nap schemes. The current study therefore aimed to assess the effects of a flexible nap opportunity on the physiological, cognitive, performance, neurophysiological and subjective responses of a group of non shift workers over the course of a three-day simulated night shift regime. Additional foci were the effects of the nap condition on the extent of the circadian adaptation of the subjects to the irregular work schedule and the circadian-related influences associated with being awake during the night. 36 subjects – 18 males and 18 females – were recruited to participate in the current study. The data collection spanned twelve days, during which four, three-day long shift cycles were set up: three night shift cycles and one day shift cycle. During each night shift cycle, three separate experimental conditions were staggered, namely the nap condition, the no nap condition and a booster break condition (a collaborative study that completed the setup). The day shift served as a further comparison. Each cycle comprised of 12 subjects, which meant there were four subjects per condition during each cycle. The shifts were 8 hours in duration, with the no nap group following a standard break schedule evinced in industry. The three breaks taken during the shifts amounted to a total time of 1 hour. The nap group was afforded a 1 hour flexible nap opportunity between 00h00 and 03h00 with no other breaks. Therefore, both conditions had the same amount of work time. During the shifts, subjects performed two simple, low arousal tasks (beading and packing) and completed a test battery roughly every two hours which was comprised of physiological, performance, neurophysiological and subjective measures. It was found that the inclusion of the nap opportunity significantly improved output performance and response time during a low precision, modified Fitts tapping task over the course of three night shifts, relative to no napping. Physiologically, napping resulted in higher heart rate frequency measures by the end of the shifts, which were also accompanied by significant reductions in subjective sleepiness ratings during all iii the night shifts. The nap group’s responses in this case, did not differ significantly from those of the day shift. Both simple reaction time and memory performances improved as a result of the nap inclusion, but only during the third night shift. The majority of the measures included in the research also depicted the effects of the circadian rhythm, which was indicative of the pronounced effect that this natural biological down regulation has on performance during the night. Napping reduced the severity of these effects during beading performance and measures of subjective sleepiness. With regard to habituation, the nap opportunity also resulted in positive changes in the responses of beading performance, high precision response time, simple reaction time and both subjective sleepiness measures, relative to no napping. Sleep diary responses indicated that although sleep length and quality during the day were significantly reduced for both night-time conditions, recovery sleep (length and quality) for the nap group did not differ significantly from the no nap group. The findings of this research indicate that the inclusion of a flexible napping opportunity during the night shift had positive effects on some physiological, performance and subjective responses, and that this intervention is as beneficial as scheduled napping. Specifically, napping resulted in a significantly higher output during the beading task, relative to the no nap group despite the duration of work time being the same. As such the introduction of a flexible, self-selected nap opportunity is a practical, effective and individual-specific means of alleviating the negative effects of shift work, while improving certain performance parameters. Therefore, industries should consider its inclusion in their fatigue management programs. However, contextspecific considerations must be made, with regard work scheduling, individual differences and task demands when implementing such an intervention. This will ensure that its introduction will be well received and in time, lessen the health and work-related decrements associated with shift work.

Master of Science
Electrical and Computer Engineering
Sanjoy Das
Groundwater is one of the most vital of all common pool resources throughout the world. More than half of groundwater is used to grow crops. This research models groundwater depletion patterns within a multi-agent system framework. Irrigators are modeled as agents in the multi-agent system. The irrigation strategies adopted by the agents are investigated using game theory, under several futuristic scenarios. The consequence of unregulated groundwater extraction in each case is analyzed. A set of five irrigators, growing three crops: corn, sorghum and wheat, have been considered in this study. To allow groundwater flow, these agents are assumed to be located in adjoining farm lands. Irrigators are modeled selfish agents that strategize their irrigation patterns in order to maximize their own utilities, i.e. the difference between the total revenue obtained from crop sales and the costs incurred, including groundwater extraction costs. Due to groundwater flow, irrigators have no incentive to conserve groundwater for later use. This leads to unsustainable depletion of the resource. Using the Nikaido-Isoda relaxation algorithm, their irrigation strategies under Nash equilibrium, when no irrigator can increase its utility by unilaterally changing its strategy, are obtained. All parameters in this research are representative of Kansas. Recorded environmental and economic data of the region, along with the DSSAT software, have been used to obtain these futuristic projections. These scenarios include temperature increase, lowering of the water table, different precipitation levels, and different price increases for the crops. One of the emergent phenomena of the simulations is the adoption of crop rotation patterns by the irrigators to conserve groundwater. The irrigators grow corn, which is a more profitable yet water intensive crop in one year, and in the next, conserve water by growing sorghum instead. Another emergent outcome of this research is the viability of LEMAs. When the irrigators are subject to LEMA-level limits on groundwater use, there is a slight increase in the aggregate utility of the LEMA

Dans cette thèse on présente un concept de rationalisabilité prudente pour un modèle de jeu, on ne se limite pas a priori. L’ensemble des solutions admissibles aux équilibres de Nash. S’il existe un équilibre de Nash, le support de cet équilibre (et donc aussi le support de tous les raffinements des équilibres de Nash) est inclus dans l'ensemble des stratégies rationalisables. Cependant, pour un joueur, un élément du support d'une stratégie d'un équilibre parfait (et donc également d'un équilibre propre ou d'un équilibre séquentiel) n'est pas forcement une stratégie rationalisable prudente. Les éléments du support d'une stratégie d'un équilibre stable ou d'un équilibre persistant sont toujours inclus dans l'ensemble des stratégies rationalisables prudentes. S’il n'existe pas d'équilibre de Nash, alors le seul critère de comportement rationnel qui correspond aux axiomes imposes, est la rationalisabilite prudente
This work presents the concept of cautious rationalizability integrated into a game model which does not limit the admissible solution to the set of nash equilibria. If a nash equilibrium exist, its support - as well as the support of all of refinements of nash equilibria - is included in the set of rationalizable strategies. However, for a player an element of strategy support of a perfect equilibrium - and thus also of a proper equilibrium or of a sequential equilibrium - is not necessary to be cautious rationalizable. The elements of the strategy support of a stable equilibrium or of a persistent equilibrium are always included in the set of cautious rationalizable strategies. If nash equilibrium does not exist, the only criterion of rational behavior which corresponds to imposed axioms is the cautions rationalizabilty

Cette thèse s'intéresse aux mécanismes d'enchères au second prix pour le partage et la tarification de ressources rares. Les enchères au second prix possèdent de nombreuses propriétés remarquables: admissibilité, compatibilité d'incitation, efficacité et rationalité individuelle. Après avoir exposé et analysé la référence actuelle dans ce domaine, les enchères PSP, nous avons mis en exergue les nombreux écueils de cette règle. Nous avons introduit une nouvelle règle, les enchères NISP, qui rapportent plus au vendeur, sont plus rapides, plus simples à implémenter et allègent le trafic de signalisation. Elles vérifient bien les propriétés souhaitées. Puis nous avons montré qu'elles pouvaient s'appliquer à la vente de ressources corrélées comme les réseaux arborescents en conservant leurs propriétés remarquables. Enfin nous avons apporté notre contribution dans le domaine des jeux étendu par communication et montré que nos enchères pouvaient bénéficier des résultats obtenus
This thesis deals with second price auctions mecanisms for rare ressources sharing and pricing. The second price auctions are particulary interesting because they hold numerous interesting properties: admissibility, incentive compatibilty, efficiency and rational boundness. We presente and analyse the today's reference in this field, the PSP auctions and highlight its weaknesses. We then introduce a new mecanism so-called NISP auctions which ameliorate the seller revenu, is faster, simpler to implement and reduce the traffic signaling since each buyer can join and leave the sale easily. We prove all the properties for this new rule. We show too that it can be applied to correlated ressources sharing and pricing, tree networks are an exemple deeply studied. The mechanism keeps all its properties. Finally we contribute to pre-play communication games and show that our auction rule can benificiate of the obtained results

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This paper is about a longitudinal study of a baby, followed In his cognitive and emotional development, from the eighth to the eighteenth month of life. Based specifically In systematic observations made In the natural environment of a baby, this study has as its aim analyse the possible parallel between the construction of the notion of 'permanent object' in Piaget and the subphases of the process of 'separation-individuation'. As a whole, the view of the aspects of development leads to results that prove not the determinations of an aspect above the other, but to the conclusion that both function as structures which integrate the same interdependent system. In this sense, in the relation mother-baby, it is not the cause and the effect that are necessary to be determined, but the comprehension of the interaction between the subject and the object involved in this process. The constitution of the affective object is, therefore, closely connected to the construction of the notion of 'permanent object' during the sensorimotor period.
Este trabalho refere-se a um estudo longitudinal de um bebê, acompanhado em seu desenvolvimento cognitivo e emocional, a partir do oitavo ao décimo oitavo mês de vida. Baseando-se especificamente em observações sistemáticas realizadas no ambiente natural do bebê, este estudo tem por objetivo analisar o possível paralelo entre a construção da noção de objeto permanente em Piaget e as subfases do processo de separação-individuação. A visão integrada dos aspectos de desenvolvimento levam a resultados que evidenciam não a determinação de um aspecto sobre o outro, mas a conclusão de que ambos funcionam como estruturas que integram um mesmo sistema interdependente. Neste sentido, na relação mãe-bebê, não é a causa e o efeito que é necessário determinar, mas a compreensão da interação entre o sujeito e o objeto envolvidos neste processo. A constituição do objeto afetivo, está, portanto, estreitamente relacionado com a construção da noção de objeto permanente durante o período sensório-motor.

Les problèmes d’investissements d’énergie sont difficiles à cause des incertitudes. Certaines incertitudes peuvent être modélisées par les probabilités. Mais il y a des problèmes difficiles tels que l'évolution de technologie et la pénalisation de CO2, délicats à modéliser par des probabilités. Aussi, les travaux sur l’optimisation des systèmes d’énergie est souvent déterministe. Cette thèse s’intéresse à appliquer l’optimisation bruitée aux systèmes d’énergie. Cette thèse se concentre sur trois parties principales: les études des méthodes pour gérer le bruit, y compris utiliser des méthodes de ré-échantillonnage pour améliorer la vitesse de convergence; les applications des méthodes de portefeuilles à l’optimisation bruitée dans le continu; les applications des méthodes de portefeuilles aux cas avec incertitudes pour la planification des investissements d’énergie et aux jeux, y compris l’utilisation de l’algorithme de bandit adversarial pour calculer l’équilibre de Nash d'un jeu matriciel à somme nulle et l’utilisation de “sparsity” pour accélérer le calcul de l’équilibre de Nash
This manuscript concentrates in studying methods to handle the noise, including using resampling methods to improve the convergence rates and applying portfolio methods to cases with uncertainties (games, and noisy optimization in continuous domains).Part I will introduce the manuscript, then review the state of the art in noisy optimization, portfolio algorithm, multi-armed bandit algorithms and games.Part II concentrates on the work on noisy optimization:∙ Chapter 4 provides a generic algorithm for noisy optimization recovering most of the existing bounds in one single noisy optimization algorithm.∙ Chapter5 applies different resampling rules in evolution strategies for noisy optimization, without the assumption of variance vanishing in the neighborhood of the optimum, and shows mathematically log-log convergence results and studies experimentally the slope of this convergence.∙ Chapter 6 compares resampling rules used in the differential evolution algorithm for strongly noisy optimization. By mathematical analysis, a new rule is designed for choosing the number of resamplings, as a function of the dimension, and validate its efficiency compared to existing heuristics - though there is no clear improvement over other empirically derived rules.∙ Chapter 7 applies “common random numbers”, also known as pairing, to an intermediate case between black-box and white-box cases for improving the convergence.Part III is devoted to portfolio in adversarial problems:∙ Nash equilibria are cases in which combining pure strategies is necessary for designing optimal strategies. Two chapters are dedicated to the computation of Nash equilibria:– Chapter 9 investigates combinations of pure strategies, when a small set of pure strategies is concerned; basically, we get improved rates when the support of the Nash equilibrium is small.– Chapter 10 applies these results to a power system problem. This compares several bandit algorithms for Nash equilibria, defines parameter-free bandit algorithms, and shows the relevance of the sparsity approach dis- cussed in Chapter 9.∙ Then, two chapters are dedicated to portfolios of game methods:– Chapter 11 shows how to generate multiple policies, from a single one, when only one such policy is available. This kind of bootstrap (based on random seeds) generates many deterministic policies, and then combines them into one better policy. This has been tested on several games.– Chapter 12 extends chapter 11 by combining policies in a position-specific manner. In particular, we get a better asymptotic behavior than MCTS.Part IV is devoted to portfolios in noisy optimization:∙ Chapter 14 is devoted to portfolio of noisy optimization methods in continuous domains;∙ Chapter 15 proposed differential evolution as a tool for non- stationary bandit problems

El genoma humà està format en un 5% per low-copy repeats (LCR); segments de DNA d’entre 1 i 500 Kb que es repeteixen dues o més vegades al llarg del genoma i que comparteixen una homologia superior al 90%. L’aparellament no al·lèlic d’aquestes seqüències durant la meiosi promou la generació d’esdeveniments de recombinació homòloga no al·lèlica (NAHR) que donen lloc a reorganitzacions cromosòmiques heretables que originen un conjunt de malalties anomenades trastorns genòmics. La deleció de la regió 22q11.2, originada per la NAHR entre els LCR22, causa la síndrome de DiGeorge/velocardiofacial (SDG/VCF), un dels trastorns genòmics més freqüents en els humans. L’objectiu principal d’aquesta tesi doctoral va ser l’avaluació de les característiques genètiques que modulen la susceptibilitat a la NAHR en individus transmissors de la SDG/VCF. Es va caracteritzar la susceptibilitat a la NAHR en 8 homes amb descendència afectada per la SDG/VCF. Aquest estudi es va dur a terme a través de l’anàlisi de la freqüència d’espermatozoides portadors de delecions i duplicacions de la regió 22q11.2, i d’altres regions crítiques amb una arquitectura genòmica similar, mitjançant la hibridació in situ fluorescent (FISH) en nuclis descondensats d’espermatozoides. Els resultats obtinguts van demostrar que 2 pares transmissors de la SDG/VCF presentaven increments significatius d’espermatozoides portadors de la deleció 22q11.2 que es van atribuir a un increment de la NAHR intra-cromàtide focalitzada a la regió 22q11.2. En aquests individus, també es van analitzar els blocs de seqüències en tàndem dels LCR22-2 i LCR22-4 mitjançant la tècnica de la FISH en fibres de cromatina (fiber-FISH) obtingudes de leucòcits. Els resultats de l’anàlisi van mostrar variacions respecte la població control dels blocs de seqüències en tàndem corresponents als fòsmids L9 i K3. Aquestes variacions podrien constituir un factor de predisposició a la NAHR. Per tal de validar els resultats obtinguts mitjançant fiber-FISH, es van analitzar les variacions de seqüències paràlogues en els LCR22 cobertes pels fòsmids L9 i K3 mitjançant la reacció en cadena de la polimerasa de tipus droplet digital (ddPCR). No es van observar diferències significatives entre les poblacions d’individus transmissors de la SDG/VCF i de controls analitzades. Tot i així, els resultats van suggerir una disminució de còpies del pseudogen de AK129567 en els individus transmissors. D’altra banda, també es va analitzar la freqüència de la inversió 22q11.2 mitjançant la FISH interfàsica en limfòcits. No es va detectar cap haplotip d’inversió 22q11.2 en individus transmissors ni en controls. Així doncs, es va confirmar la inexistència d’aquest polimorfisme i es va excloure la seva implicació com a factor de predisposició per la SDG/VCF. Per últim, es va determinar el genotip de PRDM9 mitjançant PCR i seqüenciació Sanger. La comparació de les freqüències al·lèliques entre els individus transmissors i la població control no va mostrar diferències significatives. Tot i així, es va descriure un al·lel nou de PRDM9, que es va denominar L50, en un pare transmissor de la SDG/VCF que havia mostrat increments de delecions 22q11.2 en espermatozoides. Aquest resultat va suggerir que certs al·lels rars de PRDM9 podrien actuar com a factor de predisposició per la NAHR a la regió 22q11.2. En conjunt, l’avaluació dels factors de predisposició a la inestabilitat genòmica de la regió 22q11.2 va reflectir que el risc a la NAHR en aquesta regió és complex i atribuïble a la confluència de diferents característiques genètiques.
The 5% of the human genome is constituted by low copy repeats (LCRs). LCRs are DNA fragments from 1 to 500 kb in size, with at least two copies across the genome that share a high level of sequence identity (> 90%). The non-allelic alignment of these sequences during meiosis promotes non-allelic homologous recombination events (NAHR) that could lead to chromosome reorganizations which can be transmitted to the offspring. These reorganizations originate a group of diseases called genomic disorders. Deletions of the 22q11.2 region, caused by NAHR between LCR22, result in the DiGeorge/velocardiofacial syndrome (DGS/VCFS) which is one of the most frequent genomic disorder in humans. The main objective of this thesis was to evaluate the genetic features that could modulate the NAHR susceptibility in DGS/VCFS transmitting individuals. NAHR susceptibility was analysed in a total of eight men with DGS/VCFS affected progeny. This study was achieved by analysing the frequency of deletions and duplications of the 22q11.2 region, and other critical regions with a similar genomic architecture, using fluorescence in situ hybridization (FISH) in decondensed sperm nuclei. Results demonstrated that two transmitting fathers showed statistical significant increases of 22q11.2 deletions in sperm. This abnormality was attributed to an abnormal intra-chromatid NAHR activity focused on the 22q11.2 region. By applying FISH on chromatin fibers obtained from leucocytes (fiber-FISH), the blocks of tandem repeats within LCR22-2 and LCR22-4 were also evaluated for these individuals. With respect to the control population, SDG/VCF transmitting fathers showed copy number variations on tandem sequence blocks corresponding to the L9 and K3 fosmid sequences that could constitute a predisposing factor for NAHR. In order to validate fiber-FISH data, variations of paralogous sequences covered by L9 and K3 fosmids were analysed by using droplet digital polymerase chain reaction (ddPCR). Although differences between the population of DGS/VCFS transmitting parents and control individuals were not observed, the results suggested a decrease of the AK129567 pseudogene copy number in transmitting parents. The frequency of 22q11.2 inversions was also studied by applying interphase FISH in lymphocytes. The inversion haplotype was not detected in any transmitting or control individuals. Therefore, the absence of the 22q11.2 inversion polymorphism was confirmed and this genetic feature was excluded as a possible predisposing factor for DGS/VCFS. Finally, PRDM9 genotype was assessed by using PCR and Sanger sequencing. Allelic frequencies of control and DGS/VCFS transmitting individuals did not show differences. Nevertheless, we described a novel PRDM9 allele, L50, in a DGS/VCFS transmitting father with increased rates of 22q11.2 deletions in sperm. This observation suggested that certain rare alleles of PRDM9 might be a predisposing factor for NAHR at 22q11.2 region. In summary, the evaluation of predisposing factors for the genomic instability at 22q11.2 showed that the NAHR risk in this region is complex and could be attributed to a confluence of different genetic features.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior
O objetivo desse trabalho à estudarmos a controlabilidade aproximada, via estratÃgia de Stackeberg-Nash, para equaÃÃo do calor em domÃnios ilimitados, bem como para equaÃÃo da onda e para fluidos micropolares em domÃnios com fronteira variÃvel .
The purpose of this work is study the approximate controllability, via Stackelberg-Nash strategies to heat equation in unlimited domains, as well to wave equation and for micropolars fluids in domains with moving boundary.

Nous considérons dans ce travail, des problèmes d’optimisation dans des graphes de flot multi-agent. Trois types d’agents sont considérés : les agents producteurs, transporteurs et usagers et différentes variétés de topologies de réseaux sont abordées. Chaque agent transporteur contrôle la capacité d’un ensemble de routes élémentaires (arcs), ayant chacun une capacité qui peut être augmenté jusqu’à une valeur maximale moyennant un coût fixe. Les autres agents (i.e., usagers/producteurs) sont intéressés par la maximisation du flot qu’ils reçoivent. Dans ce but, ces derniers offrent une récompense aux agents transporteurs, cette récompense est proportionnelle à la valeur du flot reçu. Ce contexte multi-agent particulier est appelé jeu expansion de réseau multi-agent. La stratégie d’un agent transporteur consiste à décider de la capacité de ses arcs sachant qu’un coût supplémentaire est encouru pour toute expansion unitaire de capacité. Il reçoit en contrepartie une part de la récompense. Il est intéressé par la maximisation de son profit et se comporte en conséquence. En outre, la stratégie d’un agent producteur/usager consiste à décider de la politique de partage de sa récompense afin de maximiser le flot qu’il reçoit. Le flot total réalisé dépend finalement des stratégies de tous les agents. Dans ces jeux d’expansion de réseau multi-agent, nous nous intéressons à caractériser des stratégies stables (i.e., Equilibre de Nash) selon diverses hypothèses. En se basant sur cette caractérisation, différents cas sont définis et étudiés. L’analyse de la complexité de quelques problèmes de décision est présentée dans ce manuscrit. Nous nous intéressons particulièrement au problème de recherche d’un équilibre de Nash qui maximise la valeur du flot total circulant dans le réseau. Nous montrons que ce problème est NP-difficile au sens fort et nous montrons comment une telle stratégie peut être caractérisée par des chemins spécifiques dans des graphes résiduels. Nous proposons également un programme linéaire à variables mixtes (PLM) qui résout le problème dans le cas d’un seul agent producteur/usager et un ensemble d’agents transporteurs. Des résultats expérimentaux sont fournis pour prouver l’efficacité de notre approche
In this work, multi-agent network flow problems are addressed. Three types of agentsare considered, namely the producer, transportation and customer agents and various network topologies are tackled. Every transportation agent controls the capacities of a set of elementary routes (arcs), each one having a capacity that can be increased up to a certain point at a given cost. The other agents (i.e., customers/producers) are interesting in maximizing their flow of products. For that aim, we assume that they offer to the transportation agents a reward that is proportional to the realized flow value. This particular multi-agent framework is referred to as a multi-agent network expansion game. The transportation agent’s strategy consists in deciding upon the capacity of its arcs, an extra-cost being incurred for any capacity expansion. It receives in return a part of the total reward. It is interested in the maximization of its profit and behaves accordingly. Beside that, the producers/customers’ strategies consist in deciding the sharing policy for their reward for maximizing their own flow of products. The total network flow value eventually depends on all agents’ strategies. We take interest in characterizing and finding particular stable strategies (i.e., Nash Equilibria) that are of interest for this game under various assumptions. Based on this characterization, several cases are defined and studied. The analysis of the complexity of some decision problems is made. We particularly focus on the problem of finding a Nash Equilibrium that maximizes the value of the total flow. We prove that this problem is NP-hard in the strong sense and show how such a strategy can be characterized considering paths in specific reduced agent-networks. We also provide a mixed integer linear programming (MILP) formulation that solves the problem in the case of a single producer/customer agent and a set of transportation agents. Computational experiments are provided to prove the effectiveness of our approach

This work presents a bilevel programming framework for the design of sustainable resource networks in eco-industrial parks (EIP). First, multiobjective optimization methods are explored in order to manage the multi-criteria nature of EIP network design problems. Then, different case studies are modeled in order to minimize and maintain in equilibrium participating plants operating costs while minimizing resource consumption. Thus, the structure of the model is constituted by a bilevel programming framework where the enterprises’ plants play a Nash game between them while being in a Stackelberg game structure with the authority. This structure defines a model which, in order to be solved, has to be transformed into a MOPEC (Multiple Optimization Problems with Equilibrium Constraints) structure. Regarding the case studies, monocontaminant water networks in EIP are studied first, where the influence of plants operating parameters are studied in order to determine the most important ones to favor the symbiosis between plants. The water network is composed of a fixed number of process and water regeneration units where the maximal inlet and outlet contaminant concentrations are defined a priori. The aim is to determine which processes are interconnected and the water regeneration allocation. Obtained results highlight the benefits of the proposed model structure in comparison with traditional multiobjective approaches, by obtaining equilibrate different plants operating costs (i.e. gains between 12-25%) while maintaining an overall low resource consumption. Then, other case studies are approached by using the bilevel structure to include simultaneously energy networks in a multi-leader-multi-follower formulation where both environmental authorities are assumed to play a noncooperative Nash game. In the first case study, economic gain is proven to be more significant by including energy networks in the EIP structure. The second industrial case study explores a supply-demand utility network model where the environmental authority aims to minimize the total equivalent CO2 emissions in the EIP. In all cases, the enterprises’ plants are encouraged to participate in the EIP by the extremely favorable obtained results.

Orientador : Prof. Dr. Sergio Gregorio da Silva
Tese (doutorado) - Universidade Federal do Paraná, Setor de Ciências Biológicas, Programa de Pós-Graduação em Educação Física. Defesa: Curitiba, 21/06/2017
Inclui referências : f. 77-85
Resumo: Estudo 1: Objetivo: comparar as respostas fisiológicas, perceptuais e afetivas do exercício imposto, autosselecionado e exercício intervalado de alta intensidade (EIAI) em mulheres com excesso de gordura corporal. Métodos: 20 mulheres com sobrepeso ou obesas (35,6 ± 7,4 anos, IMC: 31,5 ± 4,3) participaram do estudo. Todos os participantes completaram seis visitas ao laboratório: (a) familiarização, (b) teste incremental até a exaustão (c) quatro sessões de exercício realizadas em dias diferentes. Os exercícios foram realizados no cicloergômetro. Cada sessão teve 20 minutos de duração e envolveu um protocolo diferente: (1) EIAI 10x60s; (2) exercício imposto (contínuo); (3) EIAI 20x30s; (4) exercício autosselecionado (contínuo). A Felt Arousal Scale (FAS), Feeling Scale (FS), Percepção Subjetiva de Esforço (PSE), Consumo de Oxigênio (VO2) e Frequência Cardíaca (FC) foram registrados durante cada sessão experimental. Para a análise da distribuição dos dados, utilizou-se o teste de Shapiro-Wilk. A ANOVA para medidas repetidas foi utilizada para comparações entre grupos com dados normais. O post hoc de Bonferroni foi usado quando diferenças foram encontradas. O teste de Friedman foi usado para dados não normais. O post hoc de Wilcoxon (com correção de Bonferroni) foi usado quando diferenças foram encontradas. O modelo circumplexo foi utilizado para apresentar as respostas afetivas. Resultados: não ocorreram diferenças nas respostas fisiológicas (% VO2pico: 72,3 ± 9,5; 71,0 ± 12,3; 73,2 ± 11,0; 72,6 ± 9,5; % FC: 81,1 ± 6,3; 80,2 ± 7,4; 80,9 ± 7,0; 79,8 ± 7,7), perceptuais (PSE: 5,0 (4,0 - 6,0); 4,5 (4,0 - 6,0); 6,0 (4,0 - 7,0); 4,0 (4,0 - 6,0)) e afetivas (FS: 2,0 (0,5 - 3,0); 2,0 (0,5 - 4,0); 0,5 (-1,0 - 3,5); 2,0 (0,5 - 4,0)) entre os exercícios imposto, autosselecionado, EIAI 10x60s e EIAI 20x30s (p < 0,05). O modelo circumplexo demonstrou que o EIAI 10x60s pode proporcionar respostas afetivas menores do que o EIAI 20x30s, exercício autosselecionado e imposto. Conclusão: o exercício autosselecionado, imposto e EIAI podem produzir respostas fisiológicas, perceptuais e afetivas similares em mulheres sobrepesa ou obesas, uma vez que a duração, o ritmo e a intensidade média sejam equivalentes; no entanto, o EIAI 10x60s deve ser considerado com cautela na prescrição exercício, pois pode promover períodos de menor resposta afetiva durante o exercício. Estudo 2: Objetivo: verificar o efeito do exercício autosselecionado e intervalado de alta intensidade (EIAI) nas respostas fisiológicas, perceptuais e afetivas de mulheres com excesso de gordura corporal: Métodos: 28 mulheres com sobrepeso ou obesas participaram do estudo. Todas foram divididas em dois grupos: EIAI (14 mulheres) e exercício autosselecionado (14 mulheres). Cada grupo foi submetido a 4 semanas de intervenção, 3 vezes por semana, em dias não consecutivos. Os exercícios foram realizados no cicloergômetro. Cada sessão teve 20 minutos de duração. A Percepção Subjetiva de Esforço (PSE), Feeling Scale (FS), Felt Arousal Scale (FAS) e Frequência Cardíaca (FC) foram mensuradas em cada sessão de exercício. O pico de consumo de oxigênio (VO2pico), a massa corporal e a potência máxima foram mensuradas pré e pós-intervenção. Para a análise da distribuição dos dados, utilizou-se o teste de Shapiro-Wilk. Para as variáveis que apresentaram distribuição normal (antropométricas, perceptuais e fisiológicas) a ANOVA two way foi utilizado para comparar os resultados pré e pós-intervenção entre o EIAI e o exercício autosselecionado. A ANOVA para medidas repetidas foi usada para observar as respostas durante as 4 semanas. O post hoc de Bonferroni foi usado quando diferenças foram encontradas. Para as variáveis de distribuição não-normal (variáveis afetivas - FS e FAS) os dados foram analisadas pelo teste de Friedman (p <0,05). O post hoc de Wilcoxon (com correção de Bonferroni) foi usado quando diferenças foram encontradas. Resultados: não houveram diferenças na massa corporal (autosselecionado - pré: 87,0 ± 14,9; pós: 87,1 ± 14,6; EIAI: pré: 83,7 ± 17,2; pós: 83,6 ± 17,4), Índice de Massa Corporal (autosselecionado - pré: 32,5 ± 3,7; pós: 32,5 ± 3,5; EIAI: pré: 31,2 ± 6,0; pós: 31,2 ± 6,0) e potência máxima (autosselecionado - pré: 144,6 ± 34,6; pós: 152,3 ± 33,5; EIAI: pré: 136,1 ± 19,0; pós: 145,7 ± 19,0) entre o pré e pós intervenção. O VO2pico melhorou em ambos os grupos após 4 semanas (autosselecionado - pré: 22,9 ± 2,9; pós: 25,4 ± 4,5; EIAI: pré: 24,8 ± 3,9; pós: 26,9 ± 4,2). O exercício autosselecionado apresentou menor % FC e PSE do que o EIAI (FC: 1 semana: 83,3 ± 5,6; 77,7 ± 7,1; 2 semana: 82,1 ± 5,5; 75,9 ± 7,6; 3 semana: 82,4 ± 6,2; 75,4 ± 8,2; 4 semana: 81,7 ± 6,1; 76,6 ± 6,3; PSE: 1 semana: 5,4 ± 1,6; 4,7 ± 1,2; 2 semana: 5,7 ± 1,5; 4,8 ± 1,2; 3 semana: 5,4 ± 1,6; 4,5 ± 1,6; 4 semana: 5,1 ± 1,6; 4,5 ± 1,7), e promoveu respostas afetivas mais prazerosas durante o exercício. Conclusão: o exercício autosselecionado e o EIAI promoveram efeito similar sobre a aptidão cardiorrespiratória após 4 semanas de treinamento. Apesar do efeito similar na aptidão aeróbia, o exercício autosselecionado foi menos intenso e mais prazeroso que no EIAI. Palavras-chave: High Intensity Interval Training; obesidade; Feeling Scale; PSE
Abstract: Study 1: Purpose: To compare the physiological, perceptual, and affective responses on imposed and self-selected exercises and high-intensity interval training (HIIT) in women with excess body fat. Methods: This study included 20 overweight or obese women (age: 35.6 ± 7.4 years, BMI: 31.5 ± 4.3). All women completed six visits to the laboratory and were subjected to the following tests and exercises: (a) familiarization, (b) incremental test until exhaustion, and (c) four sessions of exercises conducted on different days. Exercises were performed using the cycle ergometer. Each session lasted for 20 min and involved different protocols as follows: (1) HIIT 10 × 60 s, (2) imposed exercise (continuous), (3) HIIT 20 × 30 s, and (4) self-selected exercise (continuous). Felt Arousal Scale (FAS), Feeling Scale (FS), Rating Perceived Exertion (RPE), Oxygen Consumption, and Heart Rate (HR) were recorded during each experimental session. Data distribution was analyzed by the Shapiro-Wilk test. ANOVA for repeated measures was used to compare the normal data between groups. Bonferroni's post hoc test was used when differences were found. Friedman's test was used for abnormal data. Wilcoxon's post hoc test (with Bonferroni's correction) was used when differences were found. The circumplex model was used to present the affective responses. Results: No differences were observed in the physiological (% VO2peak: 72.3 ± 9.5, 71.0 ± 12.3, 73.2 ± 11.0, 72.6 ± 9.5 and % HR: 81.1 ± 6.3, 80.2 ± 7.4, 80.9 ± 7.0, 79.8 ± 7.7), perceptual (RPE: 5.0 (4.0-6.0), 4.5 (4.0-6.0), 6.0 (4.0-7.0), 4.0 (4.0-6.0)), and affective (FS: 2.0 (0.5-3.0), 2.0 (0.5-4.0), 0.5 (?1.0-3.5), 2.0 (0.5-4.0)) responses between imposed and self-selected exercise, HIIT 10 × 60 s, HIIT 20 × 30 s. (p < 0.05). The circumplex model demonstrated that HIIT 10 × 60 s can promote instances of lower affective responses than HIIT 20 × 30 s and imposed and self-selected exercises. Conclusion: HIIT, imposed, and self-selected exercises can induce similar physiological, perceptual, and affective responses in overweight or obese women because their duration, pace, and mean intensities are equivalent; however, HIIT 10 × 60 s should be considered with caution while prescribing exercises as it can promote instances of lower affective responses during exercise. Study 2: Purpose: To verify the effect of self-selected exercise and high-intensity interval training (HIIT) on the physiological, perceptual, and affective responses of women with excess body fat. Methods: This study included 20 overweight or obese women, divided into 2 groups: HIIT (14 women) and self-selected exercise (14 women). Each group underwent 4 weeks of training (HIIT 10 × 60 s or self-selected), thrice a week on nonconsecutive days. Exercises were performed using the cycle ergometer. Each session lasted for 20 min. Rating Perceived Exertion (RPE), Feeling Scale (FS), Felt Arousal Scale (FAS), and Heart Rate (HR) were measured in each exercise session. Peak oxygen consumption (VO2peak), body mass, and maximal power were measured pre- and post-intervention. The data distribution was analyzed using the Shapiro-Wilk test. Anthropometric, perceptual, and physiological variables reported normal distribution. The two-way ANOVA was used to compare the pre- and post-intervention results between HIIT and self-selected exercise. ANOVA for repeated measures was used to observe the responses during the study period. Bonferroni's post hoc test was used when differences were found. Abnormal distribution variables (affective variables, FS and FAS) were analyzed using the Friedman's test (p < 0.05). Wilcoxon's post hoc analysis (with Bonferroni's correction) was used when differences were found. Results: No differences were observed in body mass (self-selected-pre: 87.0 ± 14.9, post: 87.1 ± 14.6; HIIT-pre: 83.7 ± 17.2, post: 83.6 ± 17.4), body mass index (self-selected-pre: 32.5 ± 3.7, post: 32.5 ± 3.5; HIIT: pre: 31.2 ± 6.0, post: 31.2 ± 6.0), and maximum power (self-selected-pre: 144.6 ± 34.6, post: 152.3 ± 33.5; HIIT: pre: 136.1 ± 19.0, post: 145.7 ± 19.0) between the pre- and post-intervention groups. VO2peak improved in both groups after 4 weeks (self-selected-pre: 22.9 ± 2.9, post: 25.4 ± 4.5; HIIT-pre: 24.8 ± 3.9, post: 26.9 ± 4.2). The self-selected exercise presented lower percent HR and RPE than HIIT (HR: 1 week: 83.3 ± 5.6, 77.7 ± 7.1; 2 weeks: 82.1 ± 5.5, 75.9 ± 7.6; 3 weeks: 82.4 ± 6.2, 75.4 ± 8.2; 4 weeks: 81.7 ± 6.1, 76.6 ± 6.3 and RPE: 1 week: 5.4 ± 1.6, 4.7 ± 1.2; 2 weeks: 5.7 ± 1.5, 4.8 ± 1.2; 3 weeks: 5.4 ± 1.6, 4.5 ± 1.6; 4 weeks: 5.1 ± 1.6, 4.5 ± 1.7), and promoted more pleasant affective responses during the exercise. Conclusion: Self-selected exercise and HIIT revealed similar effects on the cardiorespiratory fitness after 4 weeks of training. Despite the similar effect on aerobic fitness, self-selected exercise was less intense and more enjoyable than HIIT. Keywords: HIIT; Feeling Scale; obese; RPE

Tese (doutorado) - Universidade Federal de Santa Catarina, Centro de Filosofia e Ciências Humanas. Programa de Pós-graduação em Psicologia
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O objetivo desse estudo foi verificar a influência da introdução de períodos de brincadeiras livres na escola sobre o desempenho motor, cognitivo e social de crianças brasileiras e portuguesas. Para responder aos objetivos propostos, a coleta dos dados foi organizada em três estudos distintos: 1) caracterização dos brinquedos; 2) influência das brincadeiras no desempenho das crianças e; 3) características do brincar. Para coletar os dados foram utilizados os recursos do survey e do quase-experimento. Participaram deste estudo 259 crianças de uma amostra brasileira e 172 crianças de uma amostra portuguesa. Todas as crianças freqüentavam os quatro primeiros anos do ensino fundamental. Um estudo mais detalhado foi realizado com 44 crianças (23 brasileiras e 21 portuguesas) do segundo ano escolar das duas amostras. Através da análise dos dados constatou-se que, quanto à caracterização dos brinquedos muitas semelhanças entre as duas amostras foram encontradas. Os meninos de ambas as amostras apresentaram predileção e maior utilização por brinquedos que exigem atividades físicas intensas. As crianças mais jovens da amostra brasileira indicaram estar mais predispostas a utilizarem os brinquedos que promovem e estimulam o desenvolvimento motor e social. Na amostra portuguesa não foram encontradas diferenças significativas na utilização dos brinquedos entre os diferentes níveis escolares das crianças. A intervenção oferecida às crianças brasileiras e portuguesas produziu resultados semelhantes. Nos dois países estudados, a introdução de períodos de brincadeira livre em ambiente escolar demonstrou provocar mudanças nos grupos experimentais. As observações das brincadeiras das crianças revelaram que, em ambas as amostras, as crianças preferem brincar de forma grupal e com brinquedos motores. Nas duas amostras os meninos apresentaram maior tendência para a segregação pelos sexos nas atividades do que as meninas. Os meninos também apresentaram preferência significativa por brincadeiras turbulentas quando comparados com as meninas. As semelhanças encontradas nas duas amostras apontam para a universalidade do comportamento de brincar enquanto que as diferenças se remetem às peculiaridades de cada contexto sócio-cultural. Conclui-se que os resultados deste estudo demonstram as vantagens da disponibilização de tempos de brincadeira livre no horário escolar, indicando que este tipo de atividade constitui-se em um ativador dos processos de desenvolvimento infantil capaz de potencializar os resultados da ação educativa.