This thesis examines nostalgia as a central literary trope of burgeoning modernisation in the mid-Victorian historical novel. Nostalgia began as a pathological form of homesickness and rapidly engaged with the perceived distancing from the past brought about by accelerated modernisation. This thesis suggests that literary representations of social, cultural and technological change echo nostalgic reactions of loss and longing. Charles Dickens, William Makepeace Thackeray, Elizabeth Gaskell and George Eliot are the primary focus of this study. Selected works by these authors are situated within the wider context of Victorian historical fiction which – following Walter Scott’s phenomenal success at the beginning of the century – became, as Franco Moretti put it, a ‘key genre’ in the Victorian era. Nostalgia’s first victims were soldiers and students displaced from home by new opportunities for mobility and new reasons to travel long distances and live away from home; it was a disease that responded to modernisation or, as Kevis Goodman has put it, ‘historical growing pains’. Nostalgia’s combination of historical and psychological dimensions, I argue, made it an aesthetic peculiarly suited to the historical novel. This thesis suggests that nostalgia was an important novelistic trope during the nineteenth century and argues that it quickly became enmeshed with the historical novel in a way that has seldom been acknowledged. Because of its medical origins, alongside its continued development as a poetic trope, nostalgia provided a language with which to intertwine emotional and psychological reactions to change with the fictional representation of real historical events. The thesis begins with a detailed account of nostalgia’s etymological history, scientific entanglements and early literary manifestations; the introduction establishes the theoretical and historical framework for the thematically organised chapters that follow. Chapter 1 explores the interlacing of personal and historical subject matter in Thackeray’s historical fiction. This chapter suggests that these interactions took place in Thackeray’s historical fiction through the mingling of nostalgic tropes in the person of his central protagonists. These figures frequently follow Scott’s Edward Waverley in being insipid spectator-participants who have been displaced from their homes and (directly or indirectly) mediate events from a perspective of nostalgic exile. Chapter 2 considers the transformation of landscape as a node of nostalgic representation. It explores the confusion of time and place in the original case studies collected by doctors studying nostalgia as a disease in relation to nineteenth-century representations of past landscapes. It suggests that part of the historicising potential of geographical places comes from this instinctive association of time with place. This overlap is exploited in the historical novel to represent changing times via changing places. Chapter 3 takes George Eliot’s Romola, frequently criticised both by contemporary commentators and subsequent critics for being too full of minutely researched objects, as a illustrative example of how things can become ‘memorative signs’ around which to build a narrative. This ‘clutter’ is reinterpreted as a system of souvenirs, artefacts and mementoes through which public history is reconstructed from excavated fragments of private life. Chapter 4 explores how mid-Victorian historical fiction tested the limits of its own nostalgic tropes. It uses Sylvia’s Lovers to probe the point at which forgetfulness overtakes the most carefully memorialised people and events. It discusses the ways in which these novels use nostalgia to represent a perilous closeness between memorialisation and erasure. It considers whether a trope premised on loss might require the threat of encroaching historical oblivion to complete its own metaphors. The thesis concludes with a coda looking forward to later nineteenth-century uses of nostalgia in historical fiction through a reading of Thomas Hardy’s The Trumpet Major (1880) and The Mayor of Casterbridge (1886).

<p>This dissertation argues that the Victorian novel created a sensory self much like that articulated by Victorian physiological psychology: a multi-centered and process-oriented body that reacts to situations and stimuli as they arise by mobilizing appropriate cognitive and nervous functions. By reading Victorian fiction alongside psychology as it was developing into a distinct scientific discipline (during the 1840s-70s), this project addresses broader interdisciplinary questions about how the interaction between literature and science in the nineteenth century provided new ways of understanding human consciousness. I show that narrative engagements with psychology in the novel form made it possible for readers to understand the modern person as productively rather than pathologically heterogeneous. To accomplish this, fiction offered author and reader an experimental form for engaging ideas posed and debated concurrently in science. </p><p>The novels I read - by authors including Charlotte Brontë, Charles Dickens, Wilkie Collins, Mary Elizabeth Braddon, and George Eliot - emerge as narrative testing grounds for constructions of subjectivity and personhood unavailable to scientific discourse. I attribute the novel's ability to create a sensory self to its formal tactics, from composites of multiple first-person accounts to strange juxtapositions of omniscience and subjectivity, from gaps and shifts in narrative to the extended form-in-process of the serial novel. My side-by-side readings of scientific and literary experiments make it clear that fiction is where we find the most innovative methods of investigation into embodied forms of human experience.</p> / Dissertation

This dissertation constitutes an interdisciplinary approach to electronic narratives, which explores the impact of recent technological developments in the literary field. The work of theorists and scholars such as Henry Jenkins, Jean Baudrillard, Lev Manovich, Albert-Laszlo Barabasi, Erving Goffman, Sherry Turkle, George Landow, Marie-Laure Ryan and Espen Aarseth, among many others, are applied to the study of how key sociological and narratological concepts acquire new meanings when implemented in an electronic environment. More specifically, this research provides evidence of how emerging media culture challenges the traditional concepts of authorship, textuality, fictionality, sequential structure, and readership, with tendencies toward anonimity, pseudonymity, collaborative authorship, hypertextual narrative structures, and the reader's involvement in the creative process. Chapter One lays out the methodology used for the study of blog-fictions. This chapter proposes an interdisciplinary approach to blogging which combines the contributions made in several fields of study within digital humanities: computer-mediated communication theory, hypertext theory, Internet ethnography, social network theory, narratology of hypertext, research on blogging and Web 2.0, ludology and performance studies. The purpose of this chapter is to conceptualize the study of blog-fictions both as an expression of information society in its current state, and as a new fictional genre that challenges traditional narrative concepts. In Chapter Two ("Blogosphere: a network of social convergences"), the center of analysis concerns the study of the blogger as a social type who reproduces its social life on the Internet. This chapter studies the peculiar and new ways in which bloggers communicate with each other and create social networks through the production and distribution of texts, hyperlinks, and multimedia artifacts. Chapter Three presents a theory of the blog-text focussing on its structure and defining features. Finally, Chapter Four analyzes how the socio-aesthetic and narrative concepts studied in previous chapters are reflected in blog-novels written in Spanish by Argentinean author Hernan Casciari. This research contributes to literary studies in general by acknowledging that electronic fictions and blog-fictions constitute an emerging literary genre with its own identifiable features, and are molded by the culture of the information society.

The origin of new coding sequence is a major puzzle in biology. The evolutionary pressures on new sequences are largely unknown, but structural constraints are thought to play a role. Previously, 3' untranslated region (UTR) conversion to open reading frame (ORF) was observed in Saccharomyces. We sought to identify genes that were polymorphic for stop codon position in S. cerevisiae and S. paradoxus. Using strain sequence data from the Saccharomyces Genome Resequencing Project, we found 1336 genes that had evidence of stop codon polymorphism. Of those, we found 62 genes that had evidence of addition to ancestral sequence that represented the conversion of ancestral 3' UTR to derived ORF. Two of these genes, YGL058W and YNL034W-A, are prime candidates for structural studies as they are short proteins with long additions and known structures. In future studies, they will be used to infer any structural constraints on newly evolving proteins.

The thesis shows how the novel The Apothecary's Tales manipulates narrative frames to create a 'simulachron', an unreliable virtual world, which problematises the reader's conceptions of the past. The novel transgresses the generic rules of 'historical fiction' to create a quality of 'historicity' located in the affect of alterity. This is argued to be a somatic response to peril deferred. The novel seeks to evoke alterity by defamiliarising linguistic norms. It does this principally through the use of 'diachronic polysemia' (lexical 'false friends') and intertexts to syncopate the reader continually between the disparate sensibilities of the 1ih and 21 st centuries. These sensibilities are simulated in the novel by the imbedment of sociolects and 'hypomemes', the tacit thoughtways supposed peculiar to a given milieu. To self-authenticate its fictions, the novel employs the 'parafictive' devices of a testamentary found artifact, an unreliable narrator and editor, plausible sociologuemes (social conventions) and ideologuemes (ideologies that inform behaviour), along with a density of period minutiae putatively grounded in the record. Any truth effects achieved are then ludically subverted by a process of critique in which structural units of the novel systematically parody the other. The novel is patterned in the structure of a nested diptych, of expositions contra posed in a mutual commentary, which extends from the defining templates of plot and episode to the micro levels of morphemes in polysemic wordplay. The tropes of nested framing and repetition of form and syntagm are defined in the thesis, respectively, as encubi/atio and 'emblematic resonance'. It is argued that these tropes, encoded in a fictive discourse that defies closure, provide a simulation of hermetic form that -when mapped upon the aleatory life world -can be productive of aesthetic affect. The agonistic elements of plot and incident in the novel are figured within the tapas of theatre, foregrounded by the duplicitous self-fashioning of the characters, and by the continual metaleptic shifts or 'frame syncopation' of narrative viewpoint, both intra and extra-diegetic. Frame syncopation is used advisedly to dilemmatise significations at both the structural and syntagmatic levels. The thesis contends that such contrived collisions of narrative interpretation may be the dynamic of affectivity in all aesthetic discourse.

My novel, Away, is mainly the story of a woman travelling alone, leaving all friends and relatives behind. She seeks out remote, beautiful and difficult places where, firstly, she has travelled to before and, then, different locations that she hasn’t known in the past. We discover that, through trauma, she has lost her sense of identity – she is in the midst of a psychological crisis that becomes clear only after the journey has been underway for some time, when circumstances force her to accept help from others. With the protagonist my aim was to portray a permanent and continuous possibility of ending, stretching endlessly. This idea is irretrievable from the notion of space, as conceived here. In Part I, I explore how not only this main character, but also, Fred embody space. Here, I examine the conception of space, taking in various perspectives raging from philosophy, geography, culture and literature studies, where we find an interdisciplinary approach to space. My contention, drawing on mainly Lefebvre’s and Massey’s investigations, is that space is produced and is simultaneously a product embodied by the characters. In addition, I analyse how a particular territory – the desert – enacts the nature of space, as defined before, in selected works by T. E. Lawrence, Wilfred Thesiger and Paul Bowles. Also, I argue that this conception of space is explored in some narratives of Paul Auster - CG, MC and CLT - in part II. Further, I examine other features of space. I contend that Auster’s writing explores space as a realm upon which Auster’s characters engage in a process of construction and disintegration both of space and their identity. Therefore, here, space is considered as a sphere constituted by a process of an ever-opened, changing and ongoing interrelation with the characters and the text. Finally, although space is presented in this essay as the major tool for investigation through composition and critical analysis, other tools, intrinsically, and I argue inseparable in fact, I proceed to an investigation, in part III, of notions of time, identity, writing and narrator in my creative work. Beside these, I investigate particularly the relationships between characters. The thesis concludes by demonstrating that writing as space evolves in more subtle, more transient and labyrinthian ways through the reference to other writers whose writing has significantly influenced my creative work.

This dissertation examines Shakespeare’s role as the most significant precursor to the Gothic author in Britain, suggesting that Shakespeare used the same literary conventions that Gothic writers embraced as they struggled to create a new subgenre of the novel. By borrowing from Shakespeare’s canon, these novelists aimed to persuade readers and critics that rather than undermining the novel’s emergent, still unassured status as an acceptable literary genre, the nontraditional aspects of their works paid homage to Shakespeare’s imaginative vision. Gothic novelists thereby legitimized their attempts at literary expression. Despite these efforts, Gothic writers did not instantly achieve the type of acceptance or admiration that they sought. The Gothic novel has consistently been viewed as a monstrous, immature literary form—either a poor experiment in the history of the novel or a guilty pleasure for those who might choose to read or to write works that fit within this mode. Writers of Gothic fictions often claim that their works emulate Shakespeare’s dramatic pathos, but they do not acknowledge that the playwright also had to navigate similar opposition to his own creative expression. While early Gothic novelists had to contend with skeptical readers and reviewers, Shakespeare had to negotiate the religious, political, and ideological limitations that members of the court, the church, and the patronage system imposed upon his craft. Interestingly, Shakespeare often succeeded in circumventing these limitations by employing the literary techniques and topoi that we recognize today as trademarks of Gothic fiction—spectacle, sublime, sepulcher, and the supernatural. Each of these concepts expresses subversive intentions toward authoritative power. For Shakespeare and the Gothic novelists, the dramatic potential of these elements corresponds directly to their ability to target the sociocultural fears and anxieties of their audience; the results are works that frighten as well as amuse. As my dissertation will show, these authors use similar imagery to surreptitiously challenge the authority figures and institutions that sought to prescribe what makes a work of fiction socially acceptable or worthy of critical acclaim.

Chemotherapy resistance in human epithelial ovarian cancer (EOC) is a significant reason for the high rate of death among patients. We hypothesized that chemotherapy- resistant EOC cells will be killed by novel drug treatments in non-adherent culture conditions. The objective of this study was to test the efficacy of novel drugs to affect platinum resistant EOC cell viability. To achieve this, the cell killing efficacy of several drugs were tested on drug-resistant EOCs growing in non-adherent cultures. Both EOC cell lines and primary EOC cells isolated from patient ascites were used for these studies. Two different classes of drugs were tested including multikinase inhibitors (dorsomorphin and LDN-193189), and an understudied class of novel chemotherapeutic agents called glycosylated antitumor ether lipids (GAELs). EOC cells were treated with the drugs at different doses alone or in combination with cisplatin. Because GAELs exhibited promising results in resistant EOC cells, the mechanism of GAEL-induced cell-death was evaluated. / October 2016

Oxidative stress is caused when there are more reactive oxygen species (ROS), than antioxidants to scavenge them, resulting in damage to cellular components. It has been implicated as a major player at multiple points in the disease process of Parkinson’s disease (PD) and many other conditions. For example, evidence suggests oxidative damage to the α-synuclein protein may affect its aggregation propensity. In addition, α-synuclein may increase ROS production. However, how this oxidative stress relates to neurodegeneration is not known. Therefore, there is a need for models of α-synucleinopathies and tools to assess the involvement of oxidative stress in the disease process. In order to model α-synucleinopathies, overexpression of the α-synuclein protein was used. A BacMam viral expression system containing human α-synuclein was generated and used to assess toxicity. α-Synuclein overexpression in undifferentiated or differentiated SH-SY5Y cells failed to show toxicity. However, the stability of α-synuclein protein expression and the cell line used may have influenced in the lack of toxicity. The current work provides important guidance for future experimental design. Flavonoids are found in plants and have antioxidant capability. AO-1-530 is a synthetic compound with a flavonoid head group and a long hydrocarbon tail. It is highly cell permeable and localises to the mitochondria. In order to investigate its protective properties, toxin-induced oxidative stress cell assays were established. AO-1-530, in the low micromolar range, was protective against high doses of tert-butyl hydroperoxide (tBHP), whereas natural antioxidants, such as myricetin and quercetin, showed limited protection or required at least 10-fold higher concentrations to achieve similar protection. The ability of AO-1-530 to directly scavenge radicals was assessed cell-free in solution and in a cell-based assay. In solution the mechanism of action was investigated by electron paramagnetic resonance (EPR) spectroscopy. AO-1-530 had similar scavenging ability to myricetin, but was a slightly stronger scavenger than quercetin. The intracellular scavenging ability was quantified by CellROX® Deep Red live imaging. Although the compounds had similar cell-free scavenging abilities, AO-1-530 significantly out-performed both myricetin and quercetin in the intracellular assay, suggesting the mitochondrial localisation is critical to its highly protective properties. AO-1-530 is a powerful, novel tool to study the involvement of oxidative stress in diverse disease models.

This thesis examines the works of Peacock and the early periodical contributions of Thackeray in the light of recent twentieth-century critical interpretations of satire. In particular, attention to Peacock's use of elements of the Menippean sub-genre in his satirical fiction offers a reassessment of his place in the literary tradition. While Thackeray's early writings demonstrate some characteristics of Menippean satire, a review of his work from the broader perspective of Bakhtin's exposition of carnival influences in serio-comic literature provides a new understanding of the origins and uses of his narratorial devices. A comparison of the work of the two authors, within the time constraint of the first half of the nineteenth century, illustrates how nineteenth-century publishing innovations shaped literary perception of satire. Although the high status of the genre in the predominant culture of the previous century was challenged by the growth of the reading public, satire found new energy and modes of expression in the popular magazines of the period. In addition, writers facing the increasing heterogeneity of new reading audiences, were forced to reconsider their personal ideals of authorship and literature, while renegotiating their position in the literary marketplace. Organized in six chapters, the discussion opens with an account of traditional interpretations of satire, and goes on to examine recent analyses of the genre. The second chapter focuses on the relevance of these new interpretations to the work of Peacock and Thackeray and the extent to which the use of Menippean forms of satire enabled each to challenge the established opinions of their period. Changes in concepts of reading and writing and innovations in modes of publication form the substance of the third chapter and this is followed by an analysis of the work of both writers, using Bakhtin's interpretation of the Menippean sub-genre in the broader context of serio-comic discourse and the carnival tradition, Chapter five is a comparative study of the attitudes of both writers towards contemporary literature and the final section places their work in the political context of the period. Both Peacock and Thackeray made extensive use of elements of Menippean satire in their fiction. The content of their work, however, and their modes of writing were highly individual, to some extent shaped by the different markets they supplied. Collectively, their writings illustrate two aspects of the cultural watershed of the early nineteenth century, Peacock reflecting traditional notions of authorship and Thackeray representing a new industry, regulated by the commercial considerations of supply and demand. As satirists,each succeeded in adapting the genre to satisfy both his own authorial integrity and the expectations of his readers.