Identification of novel innate immune mechanisms regulating inflammation in the gastrointestinal tract

The Gastro-Intestinal (GI) tract is a unique region in the body. Our innate immune system retains a fine homeostatic balance between avoiding inappropriate inflammatory responses against the myriad commensal microbes residing in the gut while also remaining active enough to prevent invasive pathogenic attack. The intestinal epithelium represents the frontline of this interface. It has long been known to act as a physical barrier preventing the lumenal bacteria of the gastro-intestinal tract from activating an inflammatory immune response in the immune cells of the underlying mucosa. However, in recent years, an appreciation has grown surrounding the role played by the intestinal epithelium in regulating innate immune responses, both in the prevention of infection and in maintaining a homeostatic environment through modulation of innate immune signalling systems. The aim of this thesis was to identify novel innate immune mechanisms regulating inflammation in the GI tract. To achieve this aim, we chose several aspects of regulatory mechanisms utilised in this region by the innate immune system. We identified several commensal strains of bacteria expressing proteins containing signalling domains used by Pattern Recognition Receptors (PRRs) of the innate immune system. Three such bacterial proteins were studied for their potentially subversive roles in host innate immune signalling as a means of regulating homeostasis in the GI tract. We also examined differential responses to PRR activation depending on their sub-cellular localisation. This was investigated based on reports that apical Toll-Like Receptor (TLR) 9 activation resulted in abrogation of inflammatory responses mediated by other TLRs in Intestinal Epithelial Cells (IECs) such as basolateral TLR4 activation. Using the well-studied invasive intra-cellular pathogen Listeria monocytogenes as a model for infection, we also used a PRR siRNA library screening technique to identify novel PRRs used by IECs in both inhibition and activation of inflammatory responses. Many of the PRRs identified in this screen were previously believed not to be expressed in IECs. Furthermore, the same study has led to the identification of the previously uncharacterised TLR10 as a functional inflammatory receptor of IECs. Further analysis revealed a similar role in macrophages where it was shown to respond to intracellular and motile pathogens such as Gram-positive L.monocytogenes and Gram negative Salmonella typhimurium. TLR10 expression in IECs was predominantly intracellular. This is likely in order to avoid inappropriate inflammatory activation through the recognition of commensal microbial antigens on the apical cell surface of IECs. Moreover, these results have revealed a more complex network of innate immune signalling mechanisms involved in both activating and inhibiting inflammatory responses in IECs than was previously believed. This contribution to our understanding of innate immune regulation in this region has several direct and indirect benefits. The identification of several novel PRRs involved in activating and inhibiting inflammation in the GI tract may be used as novel therapeutic targets in the treatment of disease; both for inducing tolerance and reducing inflammation, or indeed, as targets for adjuvant activation in the development of oral vaccines against pathogenic attack.

Breaking ranks: the emergence of representative associations in the Irish armed forces 1989-1992

This study contexualises the relationship between the armed forces and the civil authority in Ireland using and revising the theoretical framework advanced by Huntington. It tracks the evolution of the idea of a representive body for soldiers in the late 1980s, to the setting up of statutory associations under the Defence Amendment Act 1990. The study considers Irish soldiers political agitation and their use of peaceful democratic activities to achieve their aims. It highlights the fundamental policy arguments that were made against the idea of representation for the army and positions those arguments in the study of civil-military relations. Utilising unique access to secret Department of Defence files, it reveals in-depth ideological arguments advanced by the military authories in Ireland against independent representation. This thesis provides an academic study of the establishment of PDFORRA. It answers key questions regarding the change in the position of Irish government who were categorically opposed to the idea of representation in the army. It illustrates the involvement of other agencies such as the European Organisation of Military Associations (Euromil) reveals reciprocal support by the Irish associations to other emerging groups in Spain. Accessing as yet unpublished Department of Defence files, study analyses tension between the military authorities and the government. It highlights for the first time the role of enlisted personnel in the shaping of new state structures and successfully dismmisses Huntingtons theoretical contention that enlisted personnel are of no consequence in the study of civil-military relations. It fills a gap in our understanding, identified by Finer, as to how politicisation of soldiers takes place. This thesis brings a new dimension to the discipline of civil-military relations and creates new knowledge that will enhance our understanding of an area not covered previously.

History, revolution and the British popular novel: historical fiction in the romantic age

“History, Revolution and the British Popular Novel” takes as its focus the significant role which historical fiction played within the French Revolution debate and its aftermath. Examining the complex intersection of the genre with the political and historical dialogue generated by the French Revolution crisis, the thesis contends that contemporary fascination with the historical episode of the Revolution, and the fundamental importance of history to the disputes which raged about questions of tradition and change, and the meaning of the British national past, led to the emergence of increasingly complex forms of fictional historical narrative during the “war of ideas.” Considering the varying ways in which novelists such as Charlotte Smith, William Godwin, Mary Robinson, Helen Craik, Clara Reeve, John Moore, Edward Sayer, Mary Charlton, Ann Thomas, George Walker and Jane West engaged with the historical contexts of the Revolution debate, my discussion juxtaposes the manner in which English Jacobin novelists inserted the radical critique of the Jacobin novel into the wider arena of history with anti-Jacobin deployments of the historical to combat the revolutionary threat and internal moves for socio-political restructuring. I argue that the use of imaginative historical narrative to contribute to the ongoing dialogue surrounding the Revolution, and offer political and historical guidance to readers, represented a significant element within the literature of the Revolution crisis. The thesis also identifies the diverse body of historical fiction which materialised amidst the Revolution controversy as a key context within which to understand the emergence of Scott’s national historical novel in 1814, and the broader field of historical fiction in the era of Waterloo. Tracing the continued engagement with revolutionary and political concerns evident in the early Waverley novels, Frances Burney’s The Wanderer (1814), William Godwin’s Mandeville (1816), and Mary Shelley’s Valperga (1823), my discussion concludes by arguing that Godwin’s and Shelley’s extension of the mode of historical fiction initially envisioned by Godwin in the revolutionary decade, and their shared endeavour to retrieve the possibility enshrined within the republican past, appeared as a significant counter to the model of history and fiction developed by Walter Scott in the post-revolutionary epoch.

An Irish apostle: articulating and actualising apostolicity in the early Irish church

This thesis examines the earliest extant Latin Lives of Brigit and Patrick; Cogitosus’s Vita Brigidae and Muirchú’s Vita Patricii as evidence for a seventh-century debate on Irish apostolicity. While often dismissed as mere propaganda, this thesis shows they are highly sophisticated demonstrations of the continuing connection that Kildare and Armagh had to their patron saints and their authority. It examines the importance of this connection for concepts of ecclesiastical organisation, teaching authority and episcopal succession against the backdrop of the seventh-century Easter question in the Insular Church. This will show that apostolicity was considered to be intrinsically linked with orthodoxy and universality. A textual focus brings forth general patristic themes and ideas that Irish hagiographers evoked through specific words and phrases. The thesis contextualises hagiographical material using evidence from Hiberno-Latin and early Insular exegetical commentaries, referring to major patristic exegetes such as Origen, Jerome, Augustine, and Gregory the Great as support. The introduction discusses the importance of apostolic ideology for the seventh-century Irish Church, and outlines a methodology for examining such abstract themes. The first chapter looks at how developments in apostolic ideology led to ideas of apostolic primacy seen in the Insular material. Chapters two, three, and four examine metaphors of food and feeding, the fountain and the stream, and the head and the body, as significant articulations of apostolicity. Chapter five examines how corporeal relics were understood as the visible proof of this continuity and preserved a saint’s authority for their episcopal heirs. Chapter six looks at how Muirchú engaged with Patrick’s connection to the universal Church and his self-professed lack of disciplina to reconcile his apostolicity with seventh-century norms. Chapter seven places the issues considered thus far in a thoroughly Insular context by examining how the earliest English sources present the Irish legacy in Northumbria after the synod of Whitby. Chapter eight looks at how the text of Patrick’s Confessio in the Book of Armagh relates to a wider seventh-century campaign by Armagh to rehabilitate Patrick’s apostolicity. The conclusion briefly summarizes the thesis, and suggests further avenues for researching this topic in the Insular material

“Fiction makes a better job of the truth”: dialogism, oppositional consciousness and re-membering in the novels of Helena María Viramontes

This thesis comprises close textual analyses of Chicana author Helena María Viramontes' two published novels, Under the Feet of Jesus (1995) and Their Dogs Came With Them (2007). These analyses fall under three broad frameworks: space, time and body. Chapter One engages with the first of these frameworks, space, and explores concepts of cognitive mapping and heteroptopias. Chapter Two, which looks at time, employs theories of intertextuality and the palimpsest, while Chapter Three looks at the interrrelationship between mythology and images of the body in the texts. This study emerges five years after the publication of Viramontes' last novel, Their Dogs Came With Them, but offers fresh insight into the contribution of the author to both the Chicano literary tradition and also the U.S. canon through her critique of hegemonic power structures that suppress not only the voices of lower class ethnic citizens but also of ethnic writers. In particular, her work chastises the paucity of attention given to ethnic women writers in the U.S. This thesis reaffirms Viramontes' position as one of the most important writers living and writing in the U.S. today. It corroborates her work as a contestation against ethnic and gender suppression, and applauds the craftsmanship of her narrative style that delicately but decisively exposes the socio-political wrongs that occur in ocntemporary U.S. society.

The role of structure in the electrochemical performance of nanostructured metal oxides for lithium ion battery anodes

The Li-ion battery has for a number of years been a key factor that has enabled an ever increasing number of modern consumer devices, while in recent years has also been sought to power a range of emerging electric and hybrid electric vehicles. Due to their importance and popularity, a number of characteristics of Li-ion batteries have been subjected to intense work aimed at radical improvement. Although electrode material selection intrinsically defines characteristics like maximum capacity or voltage, engineering of the electrode structure may yield significant improvements to the lifetime performance of the battery, which would not be available if the material was used in its bulk form. The body of work presented in this thesis describes the relationship between the structure of electrochemically active materials and the course of the electrochemical processes occurring within the electrode. Chapter one describes the motivation behind the research presented herein. Chapter two serves to highlight a number of key advancements which have been made and detailed in the literature over recent years, pertaining to the use of nanostructured materials in Li-ion technology. Chapter three details methods and techniques applied in developing the body of work presented in this thesis. Chapter four details structural, molecular and electrochemical characteristics of tin oxide nanoparticle based electrodes, with particular emphasis on the relationship between the size distribution and the electrode performance. Chapter five presents findings of structural, electrochemical and optical study of indium oxide nanoparticles grown on silicon by molecular beam epitaxy. In chapter 6, tin oxide inverted opal electrodes are investigated for the conduct of the electrochemical performance of the electrodes under varying rate of change of potential. Chapter 7 presents the overall conclusions drawn from the results presented in this thesis, coupled with an indication of potential future work which may be explored further.

Depression and 'crises of meaninglessness' in the political-economic theology of the money-God

The thesis starts with a historical analysis of the development of depression as a concept. Through this inquiry, the controversies behind the apparent consensus about depression’s etiology and treatment are illuminated, suggesting that the understanding of the climbing rates of depression in contemporary Western civilization is still up for grabs. That’s what the thesis sets out to investigate. In order to accomplish this aim, the study builds upon the classical accounts of Georg Simmel, Émile Durkheim and the more contemporary ideas of Dany-Robert Dufour, in dialogue with an array of supplementary theoretical sources. Navigating through this ‘sea’ of extraordinary and different theories, a new avenue of reflections arises, contributing for the sophistication of the questions made about the phenomenon of depression’s rates. The fundamental argument emerging from this theoretical undertaking is that ‘crises of meaninglessness’ that pervade the collective body of Western contemporary societies have, as one of its consequences, the expansion of depression rates. Meaninglessness in contemporary times is the primary object of investigation of the thesis. The concept, in the context of this study, is not understood as merely an effect of the historical decline of shared social norms due to processes of individualization. Rather, it is claimed, it originates from and is reinforced by the ‘political-economic theology of neo-liberalism’ which becomes virtually generalized in the West, erecting money as a God. The study concludes that by undermining culturally established values, ideals, institutions and principles that may block the dissemination of commodities this new transcendence has been challenging the task of signifying life, potentializing – among other subjective difficulties – the diffusion of depression.