Magister Artium - MA / In this thesis I focus on the ways I believe Jane Austen re-imagines the idea of the hero. In popular fiction of her time, such as Samuel Richardson’s Sir Charles Grandison (1753), what we had as a hero figure served as a male monitor, to guide and instruct the female heroine. The hero begins the novel fully formed, and therefore does not go through significant development through the course of the novel. In addition to Sir Charles Grandison, I read two popular novels of Austen’s time, Fanny Burney’s Cecilia and Maria Edgeworth’s Belinda. An examination of Burney’s construction of Delvile and Edgeworth’s construction of Clarence Hervey allows me to engage with popular conceptions of the ideal hero of the late eighteenth and early nineteenth centuries. Burney and Edgeworth deviate from these ideals in order to accommodate conventions of the new Realist novel. I argue that Austen reimagines her male protagonist so that hero and heroine are well-matched and discuss, similarly, how Burney and Edgeworth create heroes as a complement to their heroines. Austen’s re-imagining of her male protagonist forms part of her contribution to the genre of the Realist novel. Austen suggests the complexity of her hero through metaphors of setting. I discuss the ways in which the descriptions of Pemberley act as a metaphor for Darcy’s character, and explore Austen’s adaptations of the picturesque as metaphors to further plot and character development. I offer a comparative reading of Darcy and Pemberley with Mr Bennet and Longbourn as suggestive in understanding the significance of setting for the heroine’s changing perceptions of the character of the hero. I explore Austen’s use of free indirect discourse and the epistolary mode in conveying “psychological or moral conflict” in relation to Captain Wentworth in Persuasion and Mr Knightley in Emma, offering some comparison to Darcy. This lends itself to a discussion on the ways in which Austen’s heroes may be read as a critique of the teachings of Lord Chesterfield’s Letters to His Son (1774). I conclude the thesis with a discussion of the ways in which Darcy has influenced the stereotype of the modern romance hero. Using two South African romance novels I suggest the ways in which the writers adapt conventions of writing heroes to cater for the new black South African middle class at which the novels are aimed. My reading of Jane Austen’s novels will highlight the significance of Austen’s work in contemporary writing, and will question present-day views that the writing of the eighteenth- and nineteenth-centuries is not relevant to African literature.

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This dissertation examines representations of prostitution in male-authored French novels from the later nineteenth century. It proposes that prostitution has a map, and that realist and naturalist authors appropriate this cartography in the Second Empire and early Third Republic to make sense of a shifting and overhauled Paris perceived to resist mimetic literary inscription. Though always significant in realist and naturalist narrative, space is uniquely complicit in the novel of prostitution due to the contemporary policy of reglementarism, whose primary instrument was the mise en carte: an official registration that subjected prostitutes to moral and hygienic surveillance, but also “put them on the map,” classifying them according to their space of practice (such as the brothel or the boulevard). It is this spatial and conceptual taxonomy, I contend, that makes the prostitute a fulcrum for authorial mapping – for the assertion of mastery over both the prostitute and the city. The first chapter reads the inscription of the tolerated brothel in novels by Huysmans and Goncourt as the mark of a nostalgic longing for old Paris and a desire for stability in a resistant urban present. Analyzing the representation of the brasserie à femmes in lesser-known works by Tabarant and Barrès, Chapter Two posits that the brasserie prostitute fuels the desires of a generation of aspirational Rastignacs by selling stories alongside beer and sex, adopting a writerly role and troubling authorial mastery of the prostitute and the city. The mobilization of prostitutional metaphors in the Rougon-Macquart is the subject of the third chapter, which argues that Zola deploys the prostitute’s entropic force to dismantle the Paris of his predecessors, Balzac and Haussmann, and clear the ground for the construction of a proper city. The final chapter demonstrates that fin-de-siècle novelist Charles-Louis Philippe makes use of the clandestinity of street prostitution in order to locate a breed of urban mapping that is not contingent on mastery. By remapping the prostitute, the dissertation proposes a new model for understanding both the nineteenth-century novel of prostitution and the lived and represented experience of a Paris that Zola termed “le mauvais lieu de l’Europe.” / Romance Languages and Literatures

Gold(I)phosphines, nucleoside analogues, and azole derivatives have been identified as promising anticancer compounds. The clinical use of these individual compounds is, however, limited due to non-selectivity associated with adverse effects and developed resistance. This study investigated seven novel gold compounds that contain either a nucleoside analogue or an azole, bound via a gold nitrogen bond, which have been designed and synthesized by Dr. Horvath under the supervision of Prof. Raubenheimer from the University of Stellenbosch. The novel compounds are divided into purinecontaining/ nucleoside analogue compounds (UH 86.2, UH 75.1, UH 58.1, UH 145.1) and azole-containing compounds (UH 107.1, UH 126.1, UH 127.1). The anticancer effects of these novel compounds were compared with that of previously described anticancer compounds [Au(dppe)2]Cl and cisplatin. The octanol/water partition coefficients (PC) of the compounds were measured in order to determine whether a correlation between the lipophilicity of the structures and the cytotoxic potency and selectivity exists. This might provide further insight for structural alterations of the compounds in order to improve their anticancer activity. The results from octanol/water PC determinations, revealed that the purine-containing compounds (UH 86.2, UH 75.1, UH 58.1, and UH 145.1), as well as the azole-containing compound, UH 127.1, exhibited hydrophilic properties, while the azole-containing compounds, UH 107.1 and UH 126.1 are lipophilic. In contrast to results by Berners-Price et al. (1999), that reported a direct proportionality between lipophilicity and cytotoxicity, for the current study, involving HeLa cells, CoLo cells, normal resting and PHA stimulated lymphocytes, no correlation was observed. For the Jurkat cell line, however, an increase in lipophilicity for the series of compounds studied was accompanied by an increase in cytotoxicity. The reason for the exception is not yet fully understood. The in vitro tumour specificity of each compound was established with cytotoxicity assays on various cancer cell lines and normal cell cultures. The cancer cell lines included human cervical cancer (HeLa) cells, human colon cancer (CoLo) cells, and human lymphocytic leukaemia (Jurkat) cells. The normal cell cultures included human resting lymphocytes and human phytohemaglutin (PHA) stimulated lymphocytes. From this data, the four most promising novel compounds were identified. Additional tests were performed by adding these four compounds to cancer cells including human breast cancer (MCF-7) cells, and cisplatin sensitive and resistant human ovarian cancer (A2780 and A2780cis) cells as well as normal chicken embryo fibroblasts. The tumour specificity of each compound was determined from the results obtained via the cytotoxicity assays. The compound is more selective the higher the tumour specificity. Cisplatin exhibited the highest tumour specificity, and [Au(dppe)2]Cl, the lowest. The two most promising novelcompounds were identified as UH 126.1 and UH 127.1, which was evidenced by their high tumour specificities. Further experiments were conducted with these two azolecontaining compounds by using Jurkat cells. The possible mechanism by which the novel compounds induce cytotoxicity was investigated with flow cytometric analysis. The effects of the compounds on the cell death pathway, the mitochondrial membrane potential and the cell cycle were determined. These results indicated that the novel compounds, UH 126.1 and UH 127.1 initiate the apoptotic cell death pathway rather than the necrotic cell death pathway. According to results, UH 126.1 and UH 127.1 influenced the status of the mitochondrial membrane potential (MMP) non-selectively and only at high concentrations. Although involvement of mitochondria in the mechanism of action cannot be excluded, results indicated that it is most likely not the primary target. After investigating the effects of the two novel azole-containing compounds on the cell cycle in Jurkat cells, it was detected that these compounds induce cell accumulation in the G1 phase of the cell cycle. It was concluded that UH 126.1 and UH 127.1 might interfere with the cell cycle indirectly, possibly by inhibition of cyclin-dependent kinases and/or other enzymes necessary for DNA replication. In an acute in vivo toxicity test during this study, results revealed drug induced adverse effects (such as significant weight loss, piloerection and diarrhoea), in the mice that received 3 and 6ìmol/kg of both UH 126.1 and UH 127.1. Evidence also revealed signs of nephrotoxicity and epatotoxicity. Due to minimal adverse effects observed in the groups that received UH 126.1 and UH 127.1 at the concentration of 1,5ìmol/kg, this is the suggested maximum tolerated dose (MTD) for these compounds. Further dose-range studies with UH 126.1 and UH 127.1 are, however, needed in order to evaluate clinicalefficacy. Copyright / Dissertation (MSc)--University of Pretoria, 2009. / Pharmacology / unrestricted

FACILITY 47 is a psychological horror novel set in Germany just after the end of World War II. The novel is written in a naturalistic style that seeks to ground paranormal genre elements in a believable world. The story follows a group of Americans, led by Michael Powell, as they seek out and become trapped within an abandoned Nazi research facility in the Harz Mountains that contains a very dangerous secret; an unknown force capable of controlling people’s actions and forcing them to destroy themselves. FACILITY 47 focuses on a character driven by greed, moral outrage at dubious American postwar policy, and a desire to create a world for himself where he is in control. In the end of the novel, Michael learns that the obsessive quest for control can have catastrophic consequences, but this discovery is made too late to save himself or his friends from the mysterious power inside the facility.

FRAGILE SAINTS is a magical realist novel set in contemporary Peru. Elsa is struggling with her recent divorce and childhood memories of her family’s silk-producing farm haunt her, so when Elsa’s dying grandmother requests to see her, she visits Peru. There, Elsa learns she has inherited a country house, near the old family hacienda, which is haunted by a dark secret. Elsa is intrigued with the house, its caretakers, and her new lover Gustavo, yet she encounters disturbing ghostly visitors. The novel is written primarily from Elsa’s point of view, as she discovers her purpose, but an omniscient narrator is employed as well, taking the reader into the family’s past. Like Gabriel Garcia Marquez’s “One Hundred Years of Solitude” and Isabel Allende’s “The House of the Spirits,” FRAGILE SAINTS uses magical realism to create a family saga where ancestral mishaps and the natural world influence the present day characters, making them vulnerable and yet also indomitable.

VISITATIONS, a novel, explores themes of haunting and desire in New York City, in two time periods. The modern-day action focuses on Alan Philips whose wife, Beth, has recently died. His efforts to resume a normal life are sabotaged by what he comes to believe is her ghost. In the parallel story, in 1924, Oliver Nathan Blackburn, a pulp writer, in the midst of a breakdown writes a story that may play a role in Beth’s death. VISITATIONS presents Alan and Oliver’s perspectives in third person narration, so that the reader is both close to and may question the subjectivity of their perceptions. The book employs a black-comic tone for the contemporary period and a more formal one for Oliver’s sections.

Spinal muscle atrophy (SMA) is an autosomal recessive neurodegenerative disease which is characterized by the loss of α motor neurons from the anterior horn of the spinal cord, resulting in progressive muscle atrophy. The loss of functional Survival motor neuron (SMN) protein due to mutations or deletion in the SMN1 gene is the cause of SMA. A potential treatment strategy for SMA is to upregulate levels of the SMN protein originating from the copy gene SMN2 which can compensate in part for the absence of the functional SMN1 gene. I have shown a novel therapeutic strategy for SMA treatment through the activation of the p38 pathway by the bacterial antibiotic anisomycin which stabilizes and increases SMN mRNA levels in vitro. Activation of the p38 pathway by anisomycin leads to cytoplasmic accumulation of HuR protein which binds to the 3’UTR of SMN transcript resulting in increased SMN levels. This opens up a novel potential therapeutic strategy for SMA. I have also identified and demonstrated a significant induction of SMN protein levels in vitro and in vivo upon treatment with FDA approved drug celecoxib, which also activates the p38 pathway. Celecoxib mitigates disease severity along with increasing the lifespan of SMA mice. Sodium valproate, trichostatin A and aclarubicin, all agents which effectively enhance SMN2 expression, have been recently shown to activate STAT5 in SMA-like mouse embryonic fibroblasts and human SMN2-transfected NSC34 cells. Given that prolactin is also known to activate the STAT5 signalling pathway, can cross blood brain barrier and is FDA approved, we elected to assess its impact on SMN levels. In this manner, I have demonstrated a significant induction in SMN mRNA and protein levels in neuronal NT2 and MN-1 cells upon treatment with prolactin. I have also demonstrated that activation of the STAT5 pathway by prolactin is necessary for this transcriptional upregulation of the SMN gene. I have found that prolactin treatment induces SMN expression in brain and spinal cord samples and that it ameliorates the disease phenotype, improving motor neuron function and increasing survival in the SMA mouse model. Presently there is no cure for SMA. This study will help in the identification and characterization of potential therapeutic compounds for the treatment of SMA.

Creative: Jongsarat is a full-length fictional novel set in Brunei. It follows the lives of two cousins as they struggle with the same decision over the course of one summer. Rijal, the black sheep of the family, must try to come to terms with his fears and his troubled past when he finds out his girlfriend is pregnant. Hana, the family's golden girl and hope for the future, fights to keep her own sins a secret as she faces losing her boyfriend to his growing love for God. Set against the backdrop of a country in which reputation and religion are inextricably intertwined, and in which traditional values are struggling to stay alive, Rijal and Hana must find a way to understand the future that they are fighting for. Jongsarat is fundamentally an exploration of the challenges traditional social and religious structures are facing as they struggle to shape modern-day Brunei. It is a study of how, when traditional culture is uninformed by the heart of religion, it leads to disenfranchisement and the hollowness of ritual. It is a story about the ways in which everyday families have to cope with the hopes and expectations each generation places on the next in an ever-changing world. Critical: By exploring the reasons why study of the religious trope has been so neglected in Chinese American literary study, this thesis seeks to understand the critical paradigms which have dominated and shaped Chinese American literary discourses. This thesis will do this by looking seriously at the history of the formation of Chinese American literature and critical study, and the ways in which it has been influenced by American social and political movements such as the feminist and civil rights movements. Having established the state of Chinese American literature and literary discourse, the thesis will then go on to examine the ways in which these external influences have caused grave misreadings which have severely limited the scope and understanding of critical discourse. This thesis will then correct these misreadings by using Amy Tan's works as a case study for performing a critical reading of the religious trope in order to open critical discourse up to new and alternative readings that will ensure the continuation of fresh, relevant and vibrant dialogue within Chinese American critical study.

A la lecture des récits de Bernanos, Gide, Kane, Achebe inscrits dans notre corpus, il ressort que l’imagerie religieuse offre un tableau composite. En effet, s’appuyant sur un ensemble de représentations, la religion varie selon les époques et les sociétés. Bien que considérant le divin comme entité influente, elle intègre des croyances et théogonies locales. Par ailleurs, la divinité ne conditionne pas toujours l’appartenance religieuse car « pas plus qu’il n’y a de religion sans société, il n’y a pas de société sans religion: une société athée serait sans doute une société sans dieu(x), mais il ne s’ensuit pas qu’elle serait sans religion ni croyance ». Il est notable que dans ces textes, l’évocation de la religion, par-delà les marques de ferveur qu’elle est susceptible de traduire, pose un problème existentiel. Plus qu’un rapport entre le divin et l’humain, c’est l’avènement d’une conscience évolutive chez l’homme dans un univers où les liens qui ont toujours forgé l’unité collective tendent à se délier. Autrement dit, la religion se veut le reflet d’un faisceau de valeurs sur la base desquelles s’inspirent les conduites humaines. Et c’est œuvrant à l’encontre d’une telle prescription que le malaise s’est instauré chez la plupart des personnages des romans. Au demeurant, de l’approche de la religion résulte le constat à la fois séduisant et décevant qu’offre l’image d’un univers pris dans le tumulte des exigences sociétales. Au regard des fictions, il s’avère que la nature du sacré émeut et se meut à travers les peuples mais, aussi, s’estompe plus qu’elle ne s’affirme, se dévoie plus qu’elle ne s’enracine. Bien qu’adossé au point de repère de la foi, l’homme est de plus en plus gagné par le vertige. Et ce malaise s’universalise car « une religion est un phénomène qui se vit collectivement ». Autrement dit, les textes dévoilent la dérive de l’être aux prises avec le mal. Mais plus qu’une lutte contre autrui, c’est plutôt l’expression d’un combat acharné contre soi afin de renaître à la première splendeur. Il est clair que l’univers des récits est peuplé d’individus dont la voix porte l’écho du divin. Une perpétuelle cohabitation entre le bien et le vice, ainsi s’établit la condition humaine telle qu’elle est présentée dans les romans. Car, que peut bien révéler le journal d’un curé, arborant la flèche de Dieu et faisant face aux démons, si ce n’est la symphonie d’une aventure ambiguë voire périlleuse. / In reading the stories of Bernanos, Gide, Achebe incorporated in our corpus, it emerges that religious imagery offers a composite picture. Based upon a set of representations, religion indeed varies according to the times and society. Though viewing the divine as an influential entity, religion implies beliefs and local theogonies. In fact, divinity doesn’t influence religious belonging for no much more than there is not religion without society, there isn’t society without religion: an atheist society undoubtedly would be a godless society but it wouldn’t mean a society devoid of religion or belief. It is worth noting that in these texts the mere mention of religion poses an existential problem beyond any fervor it is likely to stand for. More than a relationship between the divine and the human, it’s about the advent of man’s evolving conscience in a universe where bonds which have always created the collective unity tend to untie. In other words, religion is meant to be a set of values by which human behaviors are inspired. It is in fighting against such a prescription that some discomfort came to be among most characters in some novels. As a result, the observation both stunning and unsatisfactory provided by the image of a universe caught up in the turmoil of societal demands stems from the approach of religion. In view of fictions, it turns out that the nature of the sacred stirs and moves throughout all peoples but also fades away more than it shows off, leads astray more than it takes root. Though leaned to the landmark of faith, the human being is more and more subjugated by vertigo. This uneasiness becomes universal because religion is a collectively-lived phenomenon. In other words, the texts unveil human being’s drift in his struggling against evil. But more than a fight against the others, it’s rather a bitter struggle against oneself in order to be reborn to the first splendor. It is obvious that the universe of stories is peopled by individuals whose voices bear the echo of the divine. A perpetual cohabitation between good and evil, this is how the human condition is established and so depicted in the novels. For what may reveal the diary of a priest bearing the arrow of god and striving against demons except that it is the symphony of an ambiguous adventure, if not a perilous one.