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Although highly regarded by critics, Mrs. Wilson's fiction has been subject to little detailed scrutiny. This thesis attempts to trace and consolidate the threads of her thought, to demonstrate that a substantial philosophical framework supports and enhances the more obvious presentation of "the vagaries of human conduct" which make her books so pertinent. An existential humanism allows her characters to attain individual dignity and authenticity regardless of status, sex, or endowments. In Chapter II, the concept that in our society only the fittest survive is supported by Mrs. Wilson's attitude to nature, in which, however, there is always defeat with victory. The human attribute of compassion is what enables man to transcend the sorrow of humanity (as illustrated in Swamp Angel); nevertheless indiscriminate pity debilitates man and prevents him from asserting his individuality and enjoying life. In an absurd world, man's anguish is that he has the power of choice, and his freedom depends on his ability to live with his decisions. Tuesday and Wednesday is analyzed as negatively illustrating the struggle toward meaning in a purposeless world. The element of chance is discussed in Chapter III as an introduction to Mrs. Wilson's theory that man would like to, but cannot be, an island. Focussing on the "odd man out," Mrs. Wilson finds complete detachment impossible, no matter how powerful are the factors militating against real communication between individuals: chance, misunderstanding, incompatibility (many of which are directly traceable to "character"). The resultant loneliness, and the means devised by humanity to ward off the realization of its predicament is noted. Hetty Dorval represents the predicament, and Mr. Willy's gnawing emptiness the result, of an a-moral world devoid of responsibility, love, or human intercourse. Because women are "all one flow" they form a demonstrable focus for Mrs. Wilson's philosophy of continuity. Emphasizing the individuality of women, rather than their roles as wives and mothers, Mrs. Wilson is harsher, yet kinder, in her judgement than are most male novelists. Chapter IV analyzes Mrs. Wilson's fictional women and the feminine world of Hettv Dorval is discovered to contain the many aspects of women that are elaborated, in the subsequent books. The questions of sin and justice as rationalized by women seem compatible with Mrs. Wilson's over-all view of life, and it is through their ability to rationalize that they are able (although limited by their economic role), to find fulfillment. Like women, truth is illogical, difficult to define, and, in essence, paradoxical. Chapter V attempts to explicate Mrs. Wilson's belief that by admitting a "multiple" truth, one can better understand man's place in the universe, and consequently acquire tolerance. The relationship between appearance and reality is fundamental to Mrs. Wilson's philosophy, as is the paradoxical nature of morality, both of which are explored in the context of modern society. Since truth is an accretion - not something hidden behind a mask - man is always more than he appears to be, so life is a constant journey of discovery. The Conclusion assesses the value of her work which seems to reside in her ability to transcend the current nihilism prevalent in sophisticated fiction, by orienting the reader's outlook towards a positive course of action. Most people's lives are worth living, even when they are lives of quiet desperation. Like Ellen, in Love and Salt Water, what one needs is courage, dignity and compassion. / Arts, Faculty of / English, Department of / Graduate

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Das Schwermetall Kupfer ist von essentieller Bedeutung für zahlreiche zelluläre Funktionen. Aufgrund seines Redoxpotentials muss die Kupferhomöostase im Organismus eng reguliert werden. Die Schlüsselrolle spielt dabei das Kupfertransportprotein ATP7B (Wilson ATPase) in der Leber. Ein Funktionsverlust dieses Proteins wird in der autosomal-rezessiv vererbten Erkrankung Morbus Wilson deutlich. Der Kupfertransportdefekt der Hepatozyten führt zu einer Kupferüberladung in der Leber mit nachfolgender Schädigung. Ferner kommt es zu einer Kupferakkumulation im Zentralnervensystem mit neurologischen Störungen. Das bei der Erkrankung betroffene Gen ATP7B wurde 1993 kloniert. Bis heute sind über 500 krankheitsverursachende Genmutationen entdeckt worden. Eine Schlüsselfunktion dieser Enzymgruppe ist die katalytische Phosphorylierung. Die Auswirkungen von Mutationen auf die Funktion des Proteins sind jedoch nur unzureichend verstanden. ATP7B kann mit Hilfe des Baculovirusexpressionssystems hergestellt und anschließend proteinbiochemischen Untersuchungen unterzogen werden. In dieser experimentellen Arbeit wurde untersucht, ob Punktmutationen diesen Phosphorylierungsmechanismus von ATP7B beeinflussen. Dafür wurden, neben dem Wildtyp-Protein, 25 patientenspezifische und eine noch nicht beim Menschen beobachtete Mutation der Phosphorylierungsstelle D1027A als Negativkontrolle generiert und die katalytische Aktivität in einem Phosphorylierungsassay untersucht. In der vorliegenden Arbeit wurde gezeigt, dass bestimmte Punktmutationen zum Funktionsverlust von ATP7B führen. Als weiterer Mechanismus der Mutationswirkung wurde, neben der Inaktivierung von ATP7B, die Hyperphosphorylierung entdeckt. Die biochemische Charakterisierung dieser Mutationen führt zu einem tieferen Verständnis in der Pathophysiologie des Morbus Wilson und ebnet den Weg für detaillierte Untersuchungen der Genotyp-Phänotyp-Korrelation sowie für innovative Diagnostik- und Therapiestrategien.

Zugl.: Kassel, Univ., Diss., 2006

Thesis--Cornell University.

Thesis--Cornell University.

Thesis--University of Wisconsin--Madison. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 435-448).

Thesis (M.S.)--University of Wisconsin--Madison, 1961. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves [127]-132).