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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
31

Immunomodulation in the context of developing a nontypeable Haemophilus influenzae vaccine

McGrath, John Francis, n/a January 2007 (has links)
One of the major challenges of vaccine development is the conservation of immunogenicity and protective efficacy through the stages of design, production, formulation and delivery. The critical issue is that how and in what form an antigen is taken up by antigen presenting cells for proteolytic processing and presentation to the immune system bound to MHC can have dramatic effects on the activation of Th cells to drive clonal responses and induction of immunological memory. Nontypeable Haemophilus influenzae (NTHi) is a pathogenic commensal of the human respiratory tract that causes diseases with enormous socioeoconomic burdens. There is no licensed vaccine, although the potential for vaccination with outer membrane components to reduce the incidence of disease caused by NTHi has recently been demonstrated in clinical trials. The issue of immunomodulation was explored in this thesis in the context of the further evaluation of a leading NTHi vaccine candidate, the outer membrane protein OMP26. The efficacy of recombinant OMP26 (rOMP26) against NTHi challenge has been previously demonstrated in mice, rats and chinchillas. In rats, efficacy was shown to be restricted to the precursor form (containing the signal peptide) and not the mature form of rOMP26. The immunodulatory effects of changes to the rOMP26 structure were further investigated in this thesis. A range of structural variants of rOMP26 were constructed in view of reducing extraneous plasmid-derived sequence from the antigen and to introduce a unique cysteine residue as a potential conjugate site for multivalent vaccine development (Chapter 2). It was demonstrated that minor structural changes to rOMP26 such as the addition, deletion, modification or relative positioning of a single amino acid or bulky group, designed to increase the efficiency of production or introduce (cysteine) conjugation sites, altered the expression of the protein in E. coli and the immunogenicity in Balb/C mice. Furthermore, in contradiction to the published report (El-Adhami et al. 1999) and a new study in rats (Chapter 3), there was no positive effect of the signal peptide in mice, with precursor and mature forms of rOMP26 equally immunogenic (Chapter 2). Following confirmation of the need to retain the signal peptide for the immunogenicity of rOMP26 in rats, a precursor form (rOMP26VTAL) in which the conserved n-region of the signal peptide was deleted, and shown to reduce the efficiency of the cleavage of the signal peptide by signal peptidase during protein overexpression in E. coli (Chapter 3). Not only did this deletion result in an increase the yield and stability of the purified precursor protein, but rOMP26VTAL was highly immunogenic and enhanced the clearance of NTHi from the lungs of challenged rats. The potential for signal peptides to be exploited as an immune-enhancing moiety in a proteinaceous vaccine is discussed. Following the development of rOMP26VTAL as a production optimised variant of rOMP26, the next step was to test the feasibility of rOMP26VTAL as a component of a multivalent vaccine (Chapter 4). Two chimeras were constructed with LB1(f)2,1,3, a trivalent synthetic B-cell epitope from the extracellular loop 3 region of the P5 fimbrin protein of NTHi, positioned at the N- or C-terminus of rOMP26VTAL. The solubility of rOMP26VTAL was affected by the fusion, with both chimera constructs expressed only in the insoluble fraction, thus requiring a denaturing protocol for purification. Although rLB1(f)2,1,3-OMP26VTAL was expressed and purified as a more stable protein and in greater yield than rOMP26VTAL-LB1(f)2,1,3, the relative positioning of the fusion was important and rOMP26VTAL-LB1(f)2,1,3 was significantly more immunogenic in rats than rLB1(f)2,1,3-OMP26VTAL. In addition, rOMP26VTALLB1( f)2,1,3, but not rLB1(f)2,1,3-OMP26VTAL induced a significant degree of bacterial clearance following pulmonary challenge with NTHi, in levels comparable to the highly efficacious rOMP26VTAL construct. In the third part of the thesis, bacterial ghosts were evaluated as a novel mucosal delivery technology for rOMP26VTAL and rOMP26VTAL-LB1(f)2,1,3, (Chapter 5). To mimic the natural presentation of OMP26 and P5 fimbrin antigens on the cell surface of NTHi, an OmpA� sandwich fusion surface display system was developed for the outer membrane expression of the OMP26 constructs in E. coli ghosts. Following gut immunisation, but not intranasal immunisation even when co-administered with the cholera toxin�derived adjuvant CTA1-DD, bacterial ghosts were successful at presenting OMP26VTAL and rOMP26VTAL-LB1(f)2,1,3 to the immune system for the induction of enhanced clearance of NTHi in the rat pulmonary challenge model. Although this study was the first to demonstrate enhanced bacterial clearance induced by heterologous antigens expressed in the outer membrane of bacterial ghosts, future studies with ghosts will require optimisation of the expression levels of the OmpA� fusion proteins possibly to avoid cross-reactive responses related to high doses of ghosts in the inoculum. This thesis presents data that both supports the further evaluation of rOMP26 constructs for clinical trials, and has demonstrated the significant effects of structural changes, method of production and delivery system can have on the immunogenicity of a candidate vaccine. Such knowledge will contribute to and provide some new approaches for enhancing the efficiency of vaccine development against a range of diseases including those caused by NTHi. Major Outcomes: 1. Demonstration that the immunogenicity of rOMP26 antigen constructs is affected by structural modifications and their positioning within the construct, and by the delivery system. 2. Development of rOMP26VTAL, an rOMP26 construct with the KNIAK sequence deletion of the signal peptide n-region. This protein retains the immunogenicity and protective efficacy of rOMP26, but is produced with reduced cleavage of the signal peptide, resulting in higher yields and a stable protein. Lacks extraneous plasmidderived multiple cloning site sequence, and is produced in high yield as a stable protein. 3. Construction of a NTHi rOMP26VTAL-LB1(f)2,1,3 chimera antigen that induced enhanced clearance of NTHi in an acute pulmonary challenge model in rats. 4. Development of an OmpA� surface display system for the expression of rOMP26 antigen constructs in the outer membrane of E. coli/bacterial ghosts 5. Bacterial ghosts were successful as delivery vehicles for rOMP26 candidate vaccine constructs when delivered in the gut.
32

Lectures on Differentials, Generalized Differentials and on some

Michel Dubois-Violette, patricia@osiris.th.u-psud.fr 02 October 2000 (has links)
No description available.
33

Haunts of the Hill: Western Kentucky University Ghostlore

Van Ness, Arthur Gordon, IV 01 May 2012 (has links)
Western Kentucky University in Bowling Green, Kentucky, like all colleges and universities, has some interesting history. In this case, for my thesis project, I looked at specific tales regarding several buildings on campus that one hears upon arrival to campus. The buildings I included are Potter Hall, Barnes Campbell, Rodes- Harlin, Van Meter, Florence Schneider, McLean Hall, and Pearce-Ford Tower. I explored the details of the traditional oral narratives and compared those details from personal or close to personal experience. Next, I analyzed the details that have stayed the same over time or changed. To accomplish my project I went to a few of the Welcome Week campus tours, conducted audio and video interviews, archival research, as well as video recording the annual ghost walk in October given by the Communications department. The project comprises mainly of a documentary film with a complimentary written component. What I found was that the stories show some correlation between the traditional oral narratives and the first hand experiences such as names, times, experiences, and location of the events. In conclusion, I have found that in oral tales, certain details stay the same, change, and also become transformed over time. Western, like all colleges, has events that touch people’s lives and because of that impact, as well as the uniqueness of these stories, it means that certain stories will continue to be told. For further research, I would include the rest of the stories that one hears at Western including Phi Delta Theta, Delta Tau Delta, Lambda Chi Alphas, Kappa Sigma Sigma Alpha Epsilon, and Ivan Wilson as well as to continue doing further research on these oral narratives. I also would like to look at other colleges, larger and smaller, in order to get a larger sample of oral narratives at different locations over time.
34

Spirituality: A Womanist Reading of Amy Tan's "The Bonesetter's Daughter"

Pu, Xiumei 31 July 2006 (has links)
This thesis investigates the womanist theme of spirituality in Amy Tan’s novel, The Bonesetter’s Daughter. Spirituality unfolds in five linked themes: ghosts, ghostwriting, nature, bones, and memory. In structure, the thesis is composed of four parts. The Introduction proposes spirituality as a womanist way of reading The Bonesetter’s Daughter. Chapter one investigates how the spirit of Gu Liu Xin, the Chinese grandmother, plays a critical role in developing the psychological integrity of Ruth Luyi Young, the American-born Chinese granddaughter. The second chapter examines how Gu Liu Xin’s ghost helps to guide LuLing Liu Young, Liu Xin’s daughter and Ruth’s mother, out of the hazardous situation in China, and how Gu’s spirit sustains LuLing in times of alienation and hardship in America. The thesis concludes that spirituality is essential for a subjugated woman character to achieve her personal and political freedom as well as her physical and spiritual wholeness.
35

Haunted cartographies : ghostly figures and contemporary epic in the Americas /

Lorenz, Johnny Anderson, January 2000 (has links)
Thesis (Ph. D.)--University of Texas at Austin, 2000. / Vita. Includes bibliographical references (leaves 234-247). Available also in a digital version from Dissertation Abstracts.
36

The Turn of the Screw's debated phantasms: The role of the fantastic in the creation of Peter Quint and Miss Jessel

Lee, Susan Savage 01 June 2007 (has links)
When Henry James sat down to write his "amusette" as he called The Turn of the Screw (1898), he created various ambiguities in the text as a means of confusing and surprising his readers or, in other words, catching them off guard. Over a century later, the mysterious ambiance surrounding the novella has not become any clearer. While critics from Edmund Wilson to Edna Kenton have analyzed the work from a somewhat psychoanalytical perspective, stating that the ghosts of Miss Jessel and Peter Quint are merely figments of the governess's imagination, Tzvetan Todorov and Rosemary Jackson examine James's work through a fantastic approach, putting faith in the governess's narrative. From Todorov's perspective, the fantastic requires: "... the fulfillment of three conditions. First, the text must oblige the reader to consider the world of the characters as a world of living persons and to hesitate between a natural a supernatural explanation of the events described. Second, this hesitation may also be experienced by a character; thus the reader's role is so to speak entrusted to a character, and at the same time the hesitation is represented, it becomes one of the themes of the work- in the case of naïve reading, the actual reader identifies himself with the character. Third, the reader must adopt a certain attitude with regard to the text: he will reject allegorical as well as 'poetic' interpretations. (33)" In other words, Todorov's concept of hesitation involves a focus on an external point, the perspective of the reader. Yet, the reader's perspective cannot be separated from the character or thematic value of the work, thus linking the two elements through hesitation itself. Todorov explains that The Turn of the Screw fits the characteristics of the fantastic genre in regard to the reader's hesitation. Indeed, it is that very quality which has created so much critical contention in the past. Because of this hesitation, the reader must determine whether or not to believe the governess and thus, believe in the reality of the ghosts. While I will begin by defining the fantastic from Todorov's and Jackson's perspective, it is my belief that both authors fail to connect all of the elements that appear in James's text without venturing outside of the work. In my thesis, I will strictly adhere to James's novella, focusing only on the content as I connect the governess's experience to an alternative reality rather than a deviation into psychological madness. In this way, The Turn of the Screw will be revealed as a fantastic text, producing its effects on the reader through the evolution of these tendencies within the work.
37

In Derrida’s dream: a poetics of a well-made crypt

Castricano, Carla Jodey 11 1900 (has links)
This question usually arises out of Derridean deconstruction: what is the relationship between writing and death? This dissertation, however, explores Jacques Derrida's evocation of the living-dead for purposes of theorizing what might be thought of as Derrida's "poetics of the crypt." The first section, "The First Partition: Without the Door," proposes the term "cryptomimesis" to describe how, in Derrida's writing, (the) "crypt" functions as the model, method and theory of a formal poetics based upon the fantasy of incorporation. Cryptomimesis is a writing practice that leads one to understand language and writing in spatial terms of the crypt-a contradictory topography of inside/outside. Such writing also produces a radical psychological model of the individual and collective "self" configured in terms of phantoms, haunting and (refused) mourning. This dissertation also argues that Derrida's poetics of the crypt exist in a certain relationship of correspondence with the Gothic and examines how Derrida's writing intersects or "folds" into that genre, taking as a premise that each is already inhabited, even haunted, by the other. Sections such as "'Darling,' It Said": Making a Contract With the Dead," and "The Question of theTomb," develop this notion of "correspondence" by examining a set of texts written by two American Gothic writers. The discussion posits that the works of Edgar Allan Poe and Stephen King give insight into Derrida's preoccupation with inheritance and legacy while illuminating his concern, in terms of writing, with the uncanny institution of architecture. This dissertation attempts to theorize Derrida's writing practice in spatial terms by drawing upon Nicolas Abraham and Maria Torok's theory of the phantom and the crypt. It demonstrates how cryptomimesis involves the production of an uncanny imaginary space by playing with thetic referentiality. Final sections, "An Art of Chicanery" and "Inscribing the Wholly Other: No Fixed Address," develop the notion that to suspend the thetic relation is to confound (classical) distinctions between subject and object or "self" and "other." Above all, this dissertation attempts to demonstrate how, in Derrida's work, cryptomimesis is about writing the other and how such writing, predicated upon revenance and haunting, problematizes notions of the "subject," "autobiography," and "transference" and, therefore, problematizes textuality itself.
38

Sounds of terror hearing ghosts in Victorian fiction /

McLeod, Melissa January 2007 (has links)
Thesis (Ph. D.)--Georgia State University, 2007. / Title from file title page. Michael Galchinsky, committee chair; Calvin Thomas, Lee Anne Richardson, committee members. Electronic text (181 p.) : digital, PDF file. Description based on contents viewed Feb. 7, 2008. Includes bibliographical references (p. 174-181).
39

Hauntings: representations of Vancouver's disappeared women

Dean, Ambert Richelle. January 1900 (has links)
Thesis (Ph.D.)--University of Alberta, 2009. / "A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Doctor of Philosophy in English, Department of English and Film Studies." Title from pdf file main screen (viewed on August 24, 2009).
40

Ghosts and witches in Elizabethan tragedy, 1560-1625

Fryxell, Burton Lyman, January 1937 (has links)
Thesis (Ph. D.)--University of Wisconsin--Madison, 1937. / Typescript. Includes abstract and vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 385-392).

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