<p> Abstract: How can artists uphold their creative autonomy from the dictates of capitalism without compromising their vision for social change? Max Weber made it clear that the capitalism of to-day, which has to dominate economic life, educates and selects the economic subjects which needs through a process of economic survival of the fittest. (Weber, 1958) Eleven visual artists from the Golden Horseshoe Area and the Greater Toronto Area participated in this qualitative study and provided in-depth interviews their creative work, personal struggles and insights about the current state arts community. The data suggests connections between 'starving artists' and creative autonomy. On one hand, artists who pursued their art outside the formal art market deemed they had greater autonomy but experienced greater economic insecurity and social isolation. On the other hand, artists who practiced their art within the formal art market believed they had better freedom but needed to compromise creative autonomy and their vision for social change. On the whole, both art practices seemed to have lead artists to assume the concept of Art for 'my sake,' an assertion of their self-directed will for their own purpose, reducing artists' creative motivation to produce art society and for social change. While it may be solitary, it may also be a revolutionary strategy that enhances more control and focus on the artists' rather than pursuing society for validation and economic rewards.</p> / Thesis / Master of Arts (MA)

The family trilogy, Curse of the Starving Class, Buried Child and True West, presents Sam Shepard's strong bond with his culture and his people, illustrates an intense connection with the land, and reveals a deep longing for the traditions of the past, through the dramatisation of the betrayal of the American Dream. Although obviously part of the American tradition of family drama, Shepard never completely conforms, subverting the genre by debunking the traditional family in order to make a statement about the present disintegration of the bonds of family life and modern American society. In the trilogy Shepard decries the loss of the old codes connecting with his despair at the debasement of the ideals of the past and the demise of the American Dream. Finally, the plays insist on the importance a new set of tenets to supplant the sterile ethics of modern America / M.A. (English)

The family trilogy, Curse of the Starving Class, Buried Child and True West, presents Sam Shepard's strong bond with his culture and his people, illustrates an intense connection with the land, and reveals a deep longing for the traditions of the past, through the dramatisation of the betrayal of the American Dream. Although obviously part of the American tradition of family drama, Shepard never completely conforms, subverting the genre by debunking the traditional family in order to make a statement about the present disintegration of the bonds of family life and modern American society. In the trilogy Shepard decries the loss of the old codes connecting with his despair at the debasement of the ideals of the past and the demise of the American Dream. Finally, the plays insist on the importance a new set of tenets to supplant the sterile ethics of modern America / M.A. (English)

La maladie d’Alzheimer est majoritairement sporadique et peu est connu sur les mécanismes déclenchant le développement de cette forme de la maladie. Les études sur la forme familiale ont attribué une importance particulière à la bêta-amyloïde (Aβ), un produit de clivage du précurseur de la protéine amyloïde (APP). Plusieurs facteurs de risques ont été identifiés comme déclencheurs potentiels du développement de la maladie d’Alzheimer dont le diabète de type II (T2D). En effet, la déficience de la signalisation de l’insuline par la désensibilisation des récepteurs de l’insuline (IR) dans le cerveau semble être une caractéristique commune aux deux maladies. Les effets à long terme de la résistance à l’insuline sur l’accumulation d’Aβ et sur la phosphorylation de Tau ont été étudiés, mais les effets de la perturbation aiguë des IR sont moins bien caractérisés. Aussi, les désordres métaboliques sont également des caractéristiques communes aux deux maladies. Le but de notre étude est de déterminer si la perturbation aiguë des IR peut affecter le clivage de l’APP et si la privation énergétique par le jeûne peut sensibiliser ce clivage à la perturbation aiguë des IR. Pour évaluer ceci, nous avons utilisé la Tyrphostin AG1024 à faible dose pour simuler une perturbation des IR plutôt qu’un blocage complet des récepteurs. Pour quantifié le clivage de l’APP, nous avons mesuré les changements de la quantité d’APP taille pleine totale par immunobuvardage de type Western. Pour s’assurer que les changements de la quantité d’APP taille pleine traduisait bien un clivage, nous avons développé un système de lecture par luciférase. Ce système nous permet de suivre le clivage de l’APP via l’expression de la luciférase Firefly puisque le facteur de transcription GAL4 est lié à la portion C-terminale de l’APP . Tout d’abord, nous avons observé que la perturbation aiguë des IR par la Tyrphostin mène au clivage de l’APP et que le jeûne augmente la vulnérabilité au clivage de l’APP suite à une plus petite dose de Tyrphostin. Ce clivage serait imputable à la voie amyloïdogénique puisque l’inhibition de la β-secrétase et de la γ-secrétase empêche le clivage de l’APP. Nous avons aussi montré que la perturbation des IR est nécessaire alors que la perturbation spécifique des IGF-1R n’est pas suffisante. De plus, ni l’autophagie, ni les caspases et ni le protéasomes ne semblent impliqués dans le clivage de l’APP suivant la combinaison du jeûne et de la petite perturbation des IR. L’activité de mTOR n’est également pas requise. Cependant, l’activité de la GSK3 est nécessaire au clivage et semble affecter le clivage par la γ-secrétase. Nous avons ensuite confirmé dans des cultures primaires neuronales que la combinaison du jeûne et de la perturbation aiguë des IR cause le clivage de l’APP et que la GSK3 est encore une fois fortement active. Ainsi, nos résultats suggèrent que la perturbation de la signalisation de l’insuline tel qu’observé dans le T2D augmente le clivage de l’APP via la voie amyloïdogénique et, donc, contribue à la pathologie de la maladie d’Alzheimer. / Little is known about the mechanisms that trigger the onset of Alzheimer’s disease (AD), a primarily sporadic disease. Studies on the familial form of AD attributed a particular importance to Amyloid beta (Aβ), a cleavage product of the Amyloid precursor protein (APP). Many risk factors have been identified as potential triggers of the development of AD including Type 2 diabetes (T2D). Indeed, the impairment of insulin signaling by the desensitization of insulin receptors (IR) in the brain seems to be a common hallmark of both diseases. The long term effects of IR resistance on the accumulation of Aβ and Tau hyperphosphorylation have been studied, but the acute effects of IR perturbation is less characterized. Also, both diseases show metabolic defects. Our research aimed to determine whether acute perturbation of IR signaling affects APP processing and if starving (energy deprivation) could sensitize this processing to acute perturbation of IR. To assess this, we used small doses of Tyrphostin AG1024 to simulate IR perturbations rather than a complete blocakade of the receptors. To quantify APP processing, we measured the change of total full- lenght APP by Western blot. To ensure that this change reflected APP processing we developed a luciferase based readout system. This system allowed us to monitor the occurrence of APP cleavage via GAL4-UAS Firefly luciferase driven expression because we linked GAL4 transcription factor to the C-terminal region of APP. First, we showed that IR perturbation with Tyrphostin leads to APP processing and that starving increased IR susceptibility to a smaller doses of Tyrphostin. This APP processing occurs via the amyloidogenic pathway because inhibition of β- and γ-secretase inhibited APP processing. We showed that this processing absolutely requires IR perturbation, while IGF-1R perturbation alone is insufficient. Furthermore, neither autophagy, caspases nor proteasome seemed to be implicated in APP processing following starvation and small IR perturbation. The activity of mTOR is also not required. On the contrary, GSK3 activation is necessary for the processing and seems to affect γ-secretase cleavage. We then confirmed in primary cultured neurons that the combination of acute starvation and small IR perturbation causes APP cleavage and GSK3 is again strongly activated. Taken together, our results suggest that the impairment of IR signalling seen in T2D increases the processing of APP via the amyloidogenic pathway and thereby contributes to the pathology of AD.

本文以紀德根據盾徽所提出之內在重複結構，探討美國劇作家山姆謝普的「家庭劇三部曲」。〈烈火家園〉結尾的預言故事說明了家庭成員互相毀滅的行為模式，〈埋葬的孩子〉劇中所揭發的弒子秘密與舞台上的演出相對應，〈西部實錄〉劇中的西部電影大綱正是男主角兄弟鬩牆之爭的寫照。 / Chapter I relates the American playwright Sam Shepard’s life and career. Chapter II introduces the evolution of the idea of "mise en abyme." Chapter III interprets the concluding fable in "Curse of the Starving Class" as the mise en abyme of the play. Chapter IV interprets the secret of the child murder as the duplication of the action of "Buried Child" on stage. Chapter V interprets the Western scenario in "True West" as a reflection of the two brothers’ sibling rivalry in the play.