Es stellt sich die Frage, wie diese Zellen im entzündeten Gewebe überleben können und wie sie ihren Stoffwechsel an die dortigen Bedingungen anpassen. Diese Arbeit beschreibt am Beispiel der Juvenilen Idiopathischen Arthritis (JIA) die Analyse des Stoffwechsels von CD4+ T Lymphozyten, die chronische Entzündungen antreiben undim entzündeten Gewebe lange Zeit persistieren. Pathogene CD4+ CD45RO+ PD1+ CXCR5-T Zellen wurden hierfür aus Synovialflüssigkeit von Patienten mit JIA isoliert und gezeigt, dass auch bei diesen Zellen der Stoffwechsel auf Fettsäureoxidation beruht. Wurde die Fettsäureoxidation durch Etomoxir blockiert, starben die Zellen. Die Störung des Stoffwechsels dieser Zellen könnte somit eine Option für einen neuen Therapieansatzdarstellen. Zusätzlich war die Expression des Transkriptionsfaktors Twist 1 in diesen CD4+CD45RO+ PD1+ CXCR5- T Zellen hochreguliert. Twist 1 ist ein Marker für T Lymphozyten, die in entzündetem Gewebe von Patienten mit chronisch-entzündlichen Erkrankungen der Gelenke oder des Darmes persistieren. Untersuchung in vitro ergaben außerdem, dass Twist 1 spezifisch von Th1 Lymphozyten exprimiert wird, die mehrfach restimuliert wurden. Dieser Transkriptionsfaktor wirkt einerseits der Gewebszerstörung, die von T Zellen verursacht wird, entgegen, und unterstützt anderseits die Persistenz der Zellen im Gewebe durch die Induktion der microRNA148a, die die Expression des pro-apoptotischen Proteins Bim reguliert. In dieser Arbeit zeigen wir dessen Einfluss auf die Regulation des Metabolismus von CD4+ T Lymphozyten bei chronischen Entzündungen. Dabei wird die Glycolyse verringert und vermehrt Fettsäuren synthetisiert, um die Zellen vor reaktiven oxidierenden Spezies (ROS) zu schützen. Zusätzlich konnten wir nachweisen, dass mehrfach re-stimulierte, Twist-defizienteTh1 Zellen unfähig sind, durch Fettsäureoxydation zu überleben, sondern den Stoffwechsel auf Lipid- Peroxidierung umstellen / How do CD4+ T cells adapt their metabolism for survival in the inflamed tissue? This thesis describes analysis of the metabolism of CD4 T lymphocytes driving chronic inflammation and persisting at the site of inflammation, exemplified by cells that reside in the inflamed tissue of patients with the rheumatic disease juvenile idiopathic arthritis. To specifically take aim at the CD4+ T lymphocytes persisting at the site of inflammation, it is important to determine how these cells adapt their metabolism. We show that pathogenic CD4+ CD45RO+ PD1+ CXCR5- T cells that were isolated from the synovial fluid of patients with juvenile idiopathic arthritis are dependent on a fatty acid oxidation for survival ex vivo. Their survival can be blocked by blocking FAO with Etomoxir, pointing to the option of targeting such cells by metabolic interference. Furthermore, CD4+ CD45RO+ PD1+ CXCR5- T cells had upregulated expression of Twist1, a hallmark transcription factor of T lymphocytes persisting in the inflamed tissues of patients with chronic-inflammatory diseases of joints or the gut. Expression of Twist1 is specific for Th1 lymphocytes which have repeatedly been re-stimulated in vitro, or isolated from inflamed. This transcription factor dampens immunopathology caused by the T cells and supports their persistence, by inducing microRNA148a, which regulates expression of the proapoptotic protein Bim. This thesis shows, through conditional genetic inactivation of Twist1 in CD4+ T lymphocytes, that Twist1 regulates the metabolism ofCD4 T lymphocytes of chronic inflammation, by downregulating glycolysis, promoting fatty acid synthesis and protecting the cells from ROS. Additionally, we show that Twist1 deficient repeatedly reactivated murine Th1 cells are unable to survive on fatty acid oxidation and have increased levels of lipid peroxidation.

In this article, I investigate the video game BioShock for its political and cultural work and argue that it offers a popular platform to discuss the politically charged question of choice, both inside and outside the realm of video games. In a first section, I introduce the game’s basic plot and setting, propose a way to study how video games operate narratively, and briefly discuss the ‘political’ dimension of games in general. Afterwards, I look at how BioShock is influenced by Ayn Rand’s philosophy of objectivism, a philosophy that emphasizes the importance of individual choice and self-interest, and I trace this influence specifically in the game’s main antagonist, Andrew Ryan, and its setting, the underwater city of Rapture. With these elements as a basis, I analyze how BioShock engages with the politics of choice, focusing on a major twist scene in the game to demonstrate how BioShock deals with the question of choice on a metatextual level. Reading this scene in the context of the game’s overall narrative, specifically of moral choices in the game that lead to different endings, I argue that the game metatextually connects the political question of choice inherent in objectivism to the narrative and the playing of the game, pointing to the ambivalences inherent in questions of choice, agency, and free will.

No presente trabalho apresentamos um estudo sobre a dinâmica de homeomorfismos do toro homotópicos à Dehn twists. No caso conservativo, provamos que se $f$ preserva área e tem um levantamento $\\hat$ para o cilindro com fluxo zero, então, precisamente, ou $f$ é um homeomorfismo do anel, ou possui pontos no cilindro com velocidades verticais positiva e negativa, por iteradas de $\\hat$. Isso resolve a conjectura de Boyland para essa classe de homotopia. Já no caso geral, mostramos um resultado análogo. Além disso, fornecemos uma condição extremamente simples que, quando satisfeita, implica que o conjunto de rotação vertical contém um intervalo e, portanto, que $f$ tem entropia topológica positiva. / The present thesis is concerned with the dynamics of homeomorphisms of the torus homotopic to Dehn twists. We prove that if $f$ is area preserving and it has a lift $\\hat$ to the cylinder with zero flux, then either $f$ is an annulus homeomorphism, or there are points in the cylinder with positive vertical velocity and others with negative vertical velocity, for iterates of $\\hat$. This solves a version of Boyland\'s conjecture to this setting. We extend some theorems we already obtained for Dehn twists with the area preservation hypothesis to a more general class. Finally, we also give a simple explicit condition which, when satisfied, implies that the vertical rotation set contains an interval and thus also implies positive topological entropy.

Este trabalho discutiu o estudo da inferência de carregamento e a reconstrução fratográfica da taxa de propagação da trinca por fadiga em histórias de vôos simulados do tipo Twist, mini-Twist, Falstaff e mini-Falstaff. O material estudado foi uma liga de alumínio de grau aeronáutico SAE-AMS 7475 T7351 na qual foram obtidas as propriedades mecânicas a partir dos ensaios de tração e dureza, análise química, metalográfica. Foram realizados ensaios de amplitude constante de carregamento em corpos de prova com geometria tipo C(T) extraídos de um bloco e ensaios de amplitude variável em corpos de prova com geometria tipo M(T) extraídos de uma placa. Corpos de prova do tipo C(T) foram extraídos da orientação L-T e T-L, à temperatura ambiente com diferentes espessuras para a realização de ensaios de propagação de trinca por fadiga (da/dN vs. &#916K) com distintos valores de razão de carregamento,R (0,1;0,3; 0,5; 0,7 e 0,8) de acordo com a norma ASTM-E647 (1993). Foram realizados dois tipos de ensaios de fadiga com amplitude constante de carregamento. Primeiro, o ensaio com &#916P constante para obtenção dos dados dos estágios II e III das curvas da/dN vs. &#916K para distintos valores de R e, posteriormente, o ensaio com &#916K constante e R crescente para ser utilizado no estudo da inferência de carregamento de amplitude constante a partir da relação entre a morfologia da estria, H/s e a razão de carregamento R. Adicionalmente foram realizados ensaios de tenacidade à fratura, nas direções L-T e T-L, conforme a norma ASTME1820 (1999). As taxas de propagação macroscópica e microscópica foram comparadas e boas correlações foram obtidas para um intervalo entre 0,1 a 1,0 &#956m/ciclo, mesmo com distintos R. Através da técnica proposta por Berkovitz (1995), o espectro de carregamento foi estimado para distintos valores de R, através da técnica de parametrização do fator K e os resultados foram comparados ao espectro de carregamento real imposto pela máquina de ensaio. Após os ensaios de amplitude constante de carregamento foram realizados ensaios de amplitude variável com a aplicação em corpos de prova M(T) de espectros de vôos simulados padronizados pela NLR do tipo Twist e Falstaff e seus vôos reduzidos, mini-Twist e mini- Falstaff, em uma máquina servohidráulica de ensaios dinâmicos. A partir destes ensaios notou-se que suprimir os vôos com os carregamentos menos severos influencia muito a vida da propagação da trinca de fadiga, quando vôos simulados do tipo Twist e mini-Twist, fato este não observado para o Falstaff e mini-Falstaff. Foi possível observar também o efeito da aceleração e desaceleração da trinca por fadiga observando os gráficos de d2a/dvôo vs. a obtidos dos ensaios de amplitude variável. Foi realizado um estudo da superfície de fratura do CP05 por meio da técnica fractográfica do reconhecimento de blocos marcadores sendo possível mostrar uma satisfatória reconstituição da taxa de propagação da trinca por fadiga de vôo simulado do tipo Falstaff por meio de medidas das marcações na superfície de fratura dos vôos mais severos, realizadas em imagens obtidas por MEV. / The loading inference and the fractographic reconstruction of fatigue crack propagation rate in simulated flight stories, as Twist, mini-Twist, Falstaff and mini-Falstaff were investigated in this work. The studied material was an aluminum alloy SAE-AMS 7475 T7351. Tensile and hardness tests were carried out in order to determine mechanical properties, as well as chemical and microstructure analysis of the material. C(T) specimens were extracted from a block of material for constant amplitude load testing and M(T) specimens were extracted from a plate and were tested in variable amplitude loading. The curves (da/dN vs. &#916K) for constant-amplitude loading were obtained from fatigue crack propagation tests performed in L-T and T-L directions in C(T) specimens for R (0.1; 0.3; 0.5; 0.7 and 0.8), at room temperature, according to ASTM-E647 (1993). Two different constant loading fatigue tests were performed. At constant &#916P and distinct values of R for obtaining data of stages II and III of da/dN - &#916K curves; and at constant &#916K and increasing the R ratio to be used in the inference of constant amplitude loading in the relation of H/s striation morphology (obtained from fractographic images) and the loading ratio, R. Additionally, fracture toughness tests were executed in T-L and L-T directions, according to ASTM-E1820 (1999). The macroscopic and microscopic fatigue crack propagations were compared and good correlation was obtained for the range 0.1-1.0 &#956m/cycle, for all R values. By using the K factor parametrization method, Berkovitz (1995), the loading spectrum was estimated for the distinct R-values and the results were compared to the actual spectrum imposed by the test machine. Variable amplitude tests were performed in M(T) specimens by applying simulating flight spectra normalized by NLR, as Twist, mini-Twist, Falstaff and mini-Falstaff, in a servohydraulic test machine MTS, in which a Flextest GT controller was coupled. The suppression of less severe loading flights showed a great influence in fatigue crack propagation life, in simulated flight tests Twist and mini-Twist, but not in Falstaff and mini-Falstaff. The acceleration and slowing down of fatigue crack were observed in the d2a/dflight - a curve obtained from variable loading tests. The fractured surfaces of some samples were examined by the fractographic technique of blocking marks recognition. A good reconstitution of fatigue crack propagation rate of a simulated flight like Falstaff was obtained by the measurements of marks in the fracture surfaces of the more severe flights, in MEV images.

No presente trabalho apresentamos um estudo sobre a dinâmica de homeomorfismos do toro homotópicos à Dehn twists. No caso conservativo, provamos que se $f$ preserva área e tem um levantamento $\\hat$ para o cilindro com fluxo zero, então, precisamente, ou $f$ é um homeomorfismo do anel, ou possui pontos no cilindro com velocidades verticais positiva e negativa, por iteradas de $\\hat$. Isso resolve a conjectura de Boyland para essa classe de homotopia. Já no caso geral, mostramos um resultado análogo. Além disso, fornecemos uma condição extremamente simples que, quando satisfeita, implica que o conjunto de rotação vertical contém um intervalo e, portanto, que $f$ tem entropia topológica positiva. / The present thesis is concerned with the dynamics of homeomorphisms of the torus homotopic to Dehn twists. We prove that if $f$ is area preserving and it has a lift $\\hat$ to the cylinder with zero flux, then either $f$ is an annulus homeomorphism, or there are points in the cylinder with positive vertical velocity and others with negative vertical velocity, for iterates of $\\hat$. This solves a version of Boyland\'s conjecture to this setting. We extend some theorems we already obtained for Dehn twists with the area preservation hypothesis to a more general class. Finally, we also give a simple explicit condition which, when satisfied, implies that the vertical rotation set contains an interval and thus also implies positive topological entropy.

Atualmente a maioria dos veículos de passeio, pequenos e médios, são equipados com eixo traseiro do tipo interdependente. Seu baixo custo de fabricação e instalação fácil faz dele o preferido pela indústria automotiva. Normalmente, o eixo traseiro interdependente é um conjunto soldado e sua fabricação requer um controle do processo e qualidade das juntas soldadas de alto nível, devido a uma característica típica de projeto: eixos traseiros interdependentes possuem tensões críticas nos seus cordões de solda. Neste estudo, foi avaliado o quanto alterações nos parâmetros de soldagem afetam a geometria da solda e esta, por sua vez, compromete a vida à fadiga de um eixo interdependente. Através da variação dos parâmetros primários de soldagem (corrente, tensão e velocidade de soldagem), foi criado duas classes de eixos: classe A - 22V; 235A; 9mm/seg e classe B - 29V, 302A; 15mm/seg. Estes eixos foram submetidos a um ensaio de torção com carga em amplitude constante e seus desempenhos foram medidos através da curva de vida à fadiga. A variação dos parâmetros de soldagem afetou a geometria do cordão de solda, provocando nos eixos da classe B o surgimento de defeitos como baixa penetração da solda e mordedura. O resultado da análise metalográfica indica que estes defeitos influenciaram na resistência à fadiga dos eixos. A fractografia das fraturas confirmou que as falhas ocorreram por fadiga. / Nowadays most of the light, small and medium vehicles are equipped with a twist beam rear axle. Its low-cost production and easy assembly makes it the favorite axle type for the automotive industries and suspension developers. Usually the twist beam rear axle is a welded assembly and its production request a process control and high-level quality of the welded joint, due to a typical project characteristic: twist beam rear axle have critical tensions in their welds beads. It was evaluated in this study, how much the alterations in the welding parameters affects the weld bead geometry and this, for its time, affects the fatigue life of the twist beam rear axle. Through the variation of the welding primary parameters (welding current, arc voltage and welding speed), it was manufactured two classes of the axles: class \"A\" - 22V; 235A; 9mm/seg and class \"B\" - 29V, 302A; 15mm/seg. These axles were submitted the constant amplitude fatigue torsion testing and your performance were measured through the fatigue life curve. The variation of the welding parameters affected the weld bead geometry, inducing on the class \"B\" axle, the appearance of defects as low weld penetration and undercut. The metalography investigation indicates that these defects influenced in the fatigue life resistance. The fractures fractography confirmed that the flaws happened for fatigue.

La déformation de torsion que subit un profil aérodynamique a une importance capitale car elle a une influence directe sur la valeur des incidences locales et donc sur la valeur locale des densités de portance et de traînée. L'amélioration des performances aérodynamiques passe donc par la connaissance et la maîtrise de ce vrillage. Cette thèse se propose d'y contribuer. Une des méthodes développées actuellement par de nombreux auteurs consiste à munir le profil d'actionneurs permettant de le déformer en torsion de manière à compenser tout ou partie, voire même contrer, la déformation « naturelle » de la structure. Cette méthode, dite de contrôle actif, est certes très efficace, mais elle présente des limitations car elle nécessite l'introduction d'une quantité d'énergie qui peut être importante. La méthode que nous proposons ici pour maîtriser le vrillage du profil consiste à modifier ses conditions d'équilibre interne. En solidarisant ou en désolidarisant des cloisons à l'intérieur du profil, il est possible de déplacer le centre de torsion des sections du profil sans modifier sa forme extérieure. Ces modifications internes induisent donc une modulation du moment de torsion et donc une modulation du vrillage. Ce processus ne demande que très peu d'énergie. A partir d'un profil simple, des simulations ont permis de montrer le potentiel théorique du système proposé. Trois démonstrateurs, de complexité croissante, ont également été réalisés pour évaluer les capacités du contrôle « réactif » de la torsion. La technique a été validée par la deuxième démonstration. Malheureusement, le troisième démonstrateur, beaucoup plus complexe, n'a pas permis, à l’heure actuelle, d'obtenir la validation finale. / The torsional deformation of aerodynamic profiles has to be considered with care because it induces a change in the angle of attack and therefore changes in the local densities of lift and drag forces. The improvement of the aerodynamic performances does require a good knowledge and control of the twist of the airfoil. A method currently developed by a lot of authors consists in inserting in the airfoil some actuators whose action tends to increase or reduce the ‘natural’ deformation of the structure. This method, named active control, is very effective but it has some limitations because it needs a level of energy which can be high. The method we propose to control the twist of the airfoil consists in modifying the internal elastic equilibrium of the structure. By joining or disjoining some walls inside the profile, it is possible to shift the shear center of the profile without any change of its external shape. So, these internal modifications induce variations of the torsional moment and therefore a variation of the twist angle. The process is no energy consuming. By means of a simple profile, simulations have been performed to show the theoretical potential of the proposed system. Three demonstrators have also been designed with increasing complexity to evaluate the feasibility of the ‘reactive’ control of the twist. The technique has been validated by the second demonstrator. Unfortunately, the third demonstrator, much more complex, has not shown the final demonstration.

This project is a creative production that combines image, sound, and narrative. It uses these elements to employ a twist as a device for a paradigm and genre shift in a short film text. My short film introduces a plot that is seemingly linear. Yet, the twist presents a piece of information that reveals the actual non-linear nature of the story, which in turn necessitates the re-interpretation of the plot. The aim of this project is to explore how a twist in a narrative-based short film can alter the cues and perceptions the audience receive from the plot. The project is predominantly practice-based (80%).

For optimal rotor performance in a tiltrotor aircraft the difference in the inflow and the rotor speeds between the hover and cruise flight modes suggests different blade twist and chord distributions. The blade twist rates in current tiltrotor applications are defined based upon a compromise between the figure of merit in hover and propeller efficiency in airplane mode. However, when each operation mode is considered separately the optimum blade distributions are found to be considerably different. Passive blade twist control, which uses the inherent variation in centrifugal forces on a rotor blade to achieve optimum blade twist distributions in each flight mode through the use of extension-twist coupled composite rotor blades, has been considered for performance improvement of tiltrotor aircraft over the last two decades. The challenge for this concept is to achieve the desired twisting deformations in the rotor blade without altering the aeroelastic characteristics of the vehicle. A concept referred to as the sliding mass concept is proposed in this work in order to increase the twist change with rotor speed for a closed-cell composite rotor blade cross-section to practical levels for performance improvement in a tiltrotor aircraft. The concept is based on load path changes for the centrifugal forces by utilizing non-structural masses readily available on a conventional blade, such as the leading edge balancing mass. A multilevel optimization technique based on the simulated annealing method is applied to improve the performance of the XV15 tiltrotor aircraft. A cross-sectional analysis tool, VABS together with a multibody dynamics code, DYMORE are integrated into the optimization process. The optimization results revealed significant improvements in the power requirement in hover while preserving cruise efficiency. It is also shown that about 21% of the improvement is provided through the sliding mass concept pointing to the additional flexibility the concept provides for tailoring of the structure without any additional weight penalty on the system.

A nanofilm rotation method is developed to study the rotation of nanograins and the formation of various low energy interfaces. Epitaxial NiO and Ag nanofilms are prepared by ion beam sputtering onto the (100), (110), (111) and (112) surfaces of NaCl single crystal. By overlapping of the above films with an angle difference, and annealing at relatively low temperatures the nanograins are induced to rotate till a stable interface is reached. The rotation process and the stable interfaces are determined by transmission electron microscopy. Many new interfaces between mixed planes are found, and their orientation relationships and structures are analyzed. The rotation speed increase with temperature and is fast above 200oC.