The transforming growth factor beta (TGFβ) is a cytokine that regulates a plethora of cellular processes such as cell proliferation, differentiation, migration and apoptosis. TGFβ signals via serine/threonine kinase receptors and activates the Smads to regulate gene expression. Enigmatically, TGFβ has a dichotomous role as a tumor suppressor and a tumor promoter in cancer. At early stages of tumorigenesis, TGFβ acts as a tumor suppressor by exerting growth inhibitory effects and inducing apoptosis. However, at advanced stages, TGFβ contributes to tumor malignancy by promoting invasion and metastasis. The pro-tumorigenic TGFβ potently triggers an embryonic program known as epithelial-mesenchymal transition (EMT). EMT is a dynamic process whereby polarized epithelial cells adapt a mesenchymal morphology, thereby facilitating migration and invasion. Downregulation of cell-cell adhesion molecules, such as E-cadherin and ZO-1, is an eminent feature of EMT. TGFβ induces EMT by upregulating a non-histone chromatin factor, high mobility group A2 (HMGA2). This thesis focuses on elucidating the molecular mechanisms by which HMGA2 elicits EMT. We found that HMGA2 regulates a network of EMT transcription factors (EMT-TFs), such as members of the Snail, ZEB and Twist families, during TGFβ-induced EMT. HMGA2 can interact with Smad complexes to synergistically induce Snail expression. HMGA2 also directly binds and activates the Twist promoter. We used mouse mammary epithelial cells overexpressing HMGA2, which are mesenchymal in morphology and highly invasive, as a constitutive EMT model. Snail and Twist have complementary roles in HMGA2-mesenchymal cells during EMT, and tight junctions were restored upon silencing of both Snail and Twist in these cells. Finally, we also demonstrate that HMGA2 can epigenetically silence the E-cadherin gene. In summary, HMGA2 modulates multiple reprogramming events to promote EMT and invasion.

An investigation into an adaptable morphing concept for enhancing aircraft control and performance is described in this thesis. The impetus for the work was multi-legend. Initially, the work involved identifying and optimizing winglets on a swept wing baseline configuration to enhance the controllability and aerodynamic efficiency of unmanned aerial vehicles. Moreover, the other objective was to develop a realistic skin for a morphing aircraft concept that would allow subtle, more efficient shape changes to improve aircraft efficiency. In this regard, preliminary computations were performed with Athena Vortex Lattice modelling in which varying degrees of twist, swept and dihedral angle were considered. The results from this work indicated that if adaptable winglets were employed on small scale UAVs improvements in both aircraft control and performance could be achieved. Subsequent to this computational study, novel morphing wing and/or winglet mechanisms were developed to provide efficient shape changing as well as to develop a novel alternative method for a morphing skin. This new technique was numerically optimized in ANSYS Mechanical, experimentally investigated in a wind tunnel, and also compared with a baseline aileron configuration. Afterwards, flight testing was performed with an Extra 300 78 inch remote controller aircraft with the results being compared against existing fixed wing configurations. After evaluating numerical results, from various winglet configurations investigated in AVL, selected cases were found to provide good evidence that adaptable winglets, through morphing, could provide benefits for small scale aircraft control and performance as well as offering an acceptable alternative aircraft control methodology to the current discrete, 3-axis control philosophies. Using ANSYS Mechanical for structural analysis, rib configurations were also optimised in terms of weight, stress, and displacement, as well as required twist deformation magnitudes (±6° of twist achieved). Furthermore, the skin was found to be rigid with a low rate of surface wrinkling promoting a low drag surface. Ultimately, the viability of this novel concept mechanism was validated through flight testing with similar roll authority achieved compared to traditional aileron configuration. Finally, a morphing concept also provided potential shape changing performance with smooth aerodynamic surface finish. Leading to the possibility of the concept is being a viable skin for morphing application.

The formulation of rigid supersymmetric field theories on curved space leads to a number of results on their strongly-interacting regime, crucial from both the mathematical and physical point of view, starting from Witten's topological twist of four-dimensional Yang-Mills theory. At the same time, strongly-coupled field theories may also be studied holographically via the AdS/CFT correspondence. The aim of this thesis is to study aspects of the holographic dictionary for supersymmetric theories on curved manifolds. A key aspect of the correspondence is the renormalization of gravity observables, which is realized via holographic renormalization. If the dual boundary field theory is supersymmetric, it is natural to ask whether this scheme is compatible with the rigid supersymmetry at the curved boundary. The latter requires specific geometric structures, and general arguments imply that BPS observables, such as the partition function, are invariant under certain deformations of these structures. We may then formulate a precise check of the holographic dictionary by asking whether the dual holographic observables are similarly invariant, as the free energy of the gauge theory is identified with the holographically renormalized supergravity action. In the first part of the thesis, we consider this question in N = 4 gauged supergravity in four and five dimensions for the holographic dual to the topological twists of N = 4 gauge theories on Riemannian three-manifolds and N = 2 gauge theories on Riemannian four-manifolds. We show that the renormalized on-shell action is independent of the metric on the boundary four-manifold, as required for a topological theory. We then go further, analyzing the geometry of supersymmetric bulk solutions. This allows us to show that the gravitational free energy of any smooth filling vanishes in both AdS₄/CFT₃ and AdS₅/CFT₄. In the second part of the thesis, we study the same question in minimal N = 2 gauged supergravity in four and five dimensions. In four dimensions we show that holographic renormalization precisely reproduces the expected field theory results for the dependence of the partition function on the background. Surprisingly, in five dimensions we find that no choice of standard holographic counterterms is compatible with supersymmetry, which leads us to introduce novel finite boundary terms. For a class of solutions satisfying certain topological assumptions we provide some independent tests of these new boundary terms, in particular showing that they reproduce the expected VEVs of conserved charges. We also briefly comment on the relation between these terms and boundary supercurrent anomalies.

Orientador: Alysson Fábio Ferrari / Dissertação (mestrado) - Universidade Federal do ABC. Programa de Pós-Graduação em Física, 2013

Il est actuellement bien connu que les molécules non sphériques peuvent former des mésophases (ou cristaux liquides), c'est-à-dire des phases dont les propriétés sont intermédiaires entre celles des liquides et celles des cristaux. La mésophase la plus connue est la phase nématique. Il s'agit d'une phase caractérisée par une distribution aléatoire des centres de masse des molécules, mais dans laquelle l'orientation des molécules présente une direction préférentielle, désignée par un vecteur unité appelé le directeur du nématique. Une telle phase possède donc la fluidité d'un liquide tout en présentant, tel un cristal, une biréfringence. C'est cette dernière propriété qui est exploitée dans les applications technologiques, principalement dans les dispositifs d'affichage. Dans un tel dispositif, le liquide nématique est contenu dans une cellule (il y a une cellule par pixel), et son directeur est manipulé à l'aide d'un champ extérieur, électrique ou magnétique. Pour une bonne compréhension du fonctionnement de ce dispositif, il est essentiel de connaître le profil du directeur à travers la cellule en l'absence de champ extérieur. Dans le cadre de ce travail, nous avons étudié un nématique torsadé, c'est-à-dire dont le directeur décrit une hélice à travers la cellule. Ce profil est déterminé principalement par les propriétés d'ancrage du liquide nématique sur les parois solides de la cellule. En effet, celles-ci peuvent posséder une direction d'ancrage privilégiée, qui favorise l'alignement du directeur dans une direction particulière. Nous avons considéré ici le cas de directions d'ancrage planaires, c'est-à-dire que le directeur est dans le plan des parois. Alors que l'ajout de parois identiques dans le système induit toujours une non-uniformité spatiale dans la densité du nématique (en comparaison avec un nématique en coeur de phase), l'utilisation de directions d'ancrage différentes induit une non-uniformité orientationnelle dans le directeur du nématique; dans notre cas une torsion. C'est principalement ce profil de directeur torsadé qui nous intéresse ici. L'objectif général de ce travail consiste donc à étudier les propriétés d'ancrage d'une phase nématique confinée et torsadée, d'une part par une théorie microscopique (théorie de la fonctionnelle de la densité), et d'autre part sur le plan de simulations de Monte Carlo, en particulier dans le cas où les molécules ont la forme de disques (discotiques).

This thesis looks at the criminals of Charles Dickens' Oliver Twist as a criminal type: impoverished, unattractive people who lack family roots. It establishes connections between the criminal characters themselves as well as the real-world conditions which inspired their stereotypes. The conditions of poverty and a lack of family being tied to criminality is founded in reality, while the tendency for criminals to be unattractive is based on social bias and prejudice. It also identifies conflicting ideologies in the prevailing Victorian mindset that begins to emerge as a result of research into the criminal type.

This thesis traces the transformation of graffiti as it travels from the street to the art institution by closely examining the graffiti and installations of Barry McGee ("Twist"). As a graffitist-turned-artist, McGee looked to his environment and experiences for his art, incorporating the language of graffiti into his installations. They exhibit what I describe as his ethnography of graffiti because he creates them from his unique position as a graffiti writer, representing graffiti as both an aesthetic expression and established youth culture. In order to explain this re-mediation of graffiti, the thesis aligns McGee's works with the sculptural tableaus of Edward Kienholz to emphasize his use of the narrative to bring the audience into both the aesthetic and the social world of graffiti.

Made available in DSpace on 2014-06-12T18:29:21Z (GMT). No. of bitstreams: 2 arquivo630_1.pdf: 413376 bytes, checksum: d76dc76d2a3453152d99ea1ec6e4224a (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2008 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Estuda-se aspectos relacionados às aplicações do tipo twist. Discute-se a existência e propriedades de uma função geratriz de uma aplicação do tipo twist. Depois, apresenta-se uma versão simplificada do último teorema geométrico de Poincaré. Por fim, encontra-se o resultado conhecido como teorema das curvas invariantes de Birkhoff

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The anterior cruciate ligament (ACL) contributes to normal knee function, but it is commonly injured and has poor healing capabilities. Of the current treatments available for ACL reconstruction, none replicate the long-term mechanical properties of the ACL. It was hypothesized that tissue-engineered scaffolds comprised of reconstituted type I collagen fibers would have the potential to yield a more suitable treatment for ACL reconstruction. Ultra-violet (UV) radiation and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) were investigated as possible crosslinking methods for the scaffolds, and EDC crosslinking was deemed more appropriate given the gains in strength and stiffness afforded to individual collagen fibers. Scaffolds were composed of 54 collagen fibers, which were made using an extrusion process, organized in accordance with a braid-twist design; the addition of a hydrogel (gelatin) to this scaffold was also investigated. The scaffolds were tested mechanically to determine ultimate tensile strength (UTS), Young's modulus, and viscoelastic properties. Scaffolds were also evaluated for the cellular activity of primary rat lateral collateral ligament (LCL) and medial collateral ligament (MCL) fibroblast cells after 7, 14, and 21 days. The crosslinked scaffolds without gelatin exhibited mechanical and viscoelastic properties that were more similar to the human ACL. Cellular activity on the crosslinked scaffolds without gelatin was observed after 7 and 21 days, but no significant increase was observed with time. Although more studies are needed, these results indicate that a braid- twist scaffold (composed of collagen fibers) has the potential to serve as a scaffold for ACL replacement. / Master of Science