The thesis combines creative and critical work integrated into a single text. The text is presented as the work of a PhD student whose project has been supervised by the disillusioned Professor Thrib. The student plans to write the fictionalised biography of Elsie Stewart, a working class Belfast woman whose life intersected with the defining dramas of twentieth century history. His research diary describes how he and his translator, Lempi, began to reconstruct Elsie's life from archive sources scattered across Europe, and his early output is literary prose of the sort one would expect to find in a historical novel. However, Professor Thrib has built his career on an eccentric form of post-structuralism, and pushed to breaking point by the bureaucracy and double-speak of the university, Thrib demands his student desists from using personal pronouns or any other grammatical structures that imply originative action. As the conclusion of Elsie's story is told in increasingly bizarre fragments, the student looks for answers through close readings of recent historical fictions (In Country, Libra, Midnight's Children, The Passion, Philadelphia Fire, Possession, Star Turn, and Waterland), in the theories of selected modern philosophers (Descartes, Kant, Hegel, Marx, Nietzsche, Heidegger, Lacan, Foucault, Derrida, and Baudrillard), and in the eccentric publications of Professor Thrib and other imaginary academics. Unable to account for human agency theoretically, he seeks a new writing that effaces the subject as originator of action; at the same time, however, he obsesses over the human drives of emotion, desire, and corporeal experience. As the student struggles with the bureaucracy of the university and his unrequited infatuation with his translator, what emerges is a novel approach to the question of free will and determinism that goes beyond 'death of the subject' literature. Additionally, the thesis uses skills from a range of disciplines including Creative Writing, English Literature, History, Philosophy, and Social Science, and in its interdisciplinary ambition it argues for the value of art and theory in an increasingly mercantile Higher Education sector.

The theologians of the early church sought to interpret the Christian gospel in the categories of `Mediterranean antiquity. ' The classical two-nature model of Christology has a Greek philosophical underpinning that shapes the ontological construction of the deity and humanity of Jesus Christ. Logos Christology is primarily a reflection on the hypostatic union of the Logos with the human reality of Jesus that leaves little place for a consideration of Jesus' relation to the Holy Spirit. In the light of such a limitation in classical Christology, a study of the relationship between Christology and pneumatology becomes very significant. In this regard, the recent resurgence of Spirit Christology in the West adds a new dimension to contemporary Christological reflection. The theologians who are engaged in this pursuit are of the view that Christological reflection is incomplete without reflecting upon pneumatology and vice versa. This study identifies in particular at least three approaches in the contemporary European Spirit Christologies, namely, reconstruction, replacement and complementary approaches. Norman Hook attempts to reconstruct Christ, Spirit and the Trinity from the perspective of the Hebrew understanding of the Spirit. G. W. H. Lampe, by using the symbol God as Spirit replaces Logos Christology with a Spirit Christology. Jürgen Moltmann, John D. Zizioulas and David Coffey seek ways to complement Logos Christology with Spirit Christology. While not denying the contributions of reconstruction and replacement approaches, this study adopts the complementary approach and shows that Spirit Christology not only enriches systematic theology but also is relevant to an Indian context. This is done by bringing the insights of two Indian theologians Pandipeddi Chenchiah and Swami Abhishiktänanda, who emphasise the centrality of the Spirit, in interaction with the strengths of Spirit Christology. The study ends in offering a chapter on `understanding Jesus Christ in India' using the Hindu concepts of Spirit that are expressed in the terms such as atman, antaryämin, Sakti and änanda. Drawing on some of the resources of Spirit Christology, it is argued that these concepts can explicate, illuminate and evoke some latent aspects of Christology.

CD23 has long been appreciated to be a natural, negative regulator of IgE synthesis. This understanding is due in part to animal models in which CD23 deficient or CD23 transgenic animals display exacerbated or reduced IgE levels respectively. Interestingly, CD23 is susceptible to proteolytic cleavage from the cell surface. When this occurs, CD23 loses its regulatory capability and the solubilized form can lead to pro-inflammatory events through its cytokinergic activity on macrophages. Thus, targeting this specific cleavage would be beneficial to the control of allergic disease by stabilizing CD23 at the cell surface. Inhibitor studies performed by our group as well as others indicate that the enzyme responsible for CD23 ectodomain shedding is a hydroxamate-sensitive metalloproteinase. Through collaboration with the Blobel group, we analyzed various ADAM KO mouse embryonic fibroblasts (MEFs) and found no involvement of ADAMs 8,9,12,15,17,19, and 33 in CD23 shedding, however we did find a role for ADAM10. Using ADAM10 KO MEFs and ADAM10 specific inhibitors, we discovered that ADAM10 is indeed the CD23 cleaving enzyme or “sheddase”. Thus, developing strategies that would target ADAM10 could have an effect on sCD23 release and IgE production. In the CNS, signaling through the kainate receptor (KAR) by glutamate causes an increase in ADAM10 expression. Human B cells were found to express a GluK2 containing kainate receptor and its activation increased ADAM10 expression which is in agreement with KAR activation in the CNS. Although glutamate is considered a neurotransmitter, it signals in the periphery and elevated levels are associated with certain immune disorders. A significant corresponding increase in sCD23 release is observed as well. Remarkably, this activation induced a strong increase in B cell proliferation, IgG, and IgE production and these events can be reversed through the use of NS102, a specific KAR antagonist. Thus, we report for the first time the unique presence on B cells of a neurotransmitter receptor and that activation of this receptor could serve as a novel mechanism for enhancing B cell activation and Ig production. This enhancement and control thereof has implications for allergic and autoimmune diseases. Lastly, the CD23-ADAM10 axis was examined in a non-allergic disease state, B cell chronic lymphocytic leukemia (BCLL). BCLL is characterized by a large accumulation of CD23+ cells and high levels of soluble CD23 in the sera. After further analysis, we show that ADAM10 is indeed over-expressed in BCLL and could account for the high levels seen in this patient population. Furthermore, specifically targeting ADAM10 resulted in reduced soluble CD23 release, reduced proliferation, and enhanced apoptosis induction. Taken together the novel finding that ADAM10 is involved in CD23 shedding allows for targeted therapeutic intervention of both atopic and non-atopic disease states.

This dissertation examines the work of the British philosopher and novelist Iris Murdoch. A centre concern of this work is a question Murdoch poses more than once: ‘How can we make ourselves morally better?” This question is understood to initiate a form of philosophy which is critical of much of its tradition and its understanding of reasoning and argument. It also recognises its dependence on other disciplines. Murdoch develops this form of philosophy in reply to the cultural phenomenon of secularisation. In the absence of God, she attributes tasks to philosophy formerly performed by religion. Most importantly, she advocates a concept of transcendent reality in philosophical discourse. This reality is the Good. She finds that in order to do so, she has to reconsider philosophy’s central faculty of reason. Drawing on literary, philosophical and theological sources, Murdoch develops an understanding of reason and argument in which images, imagery and imagination are central. This study has three objectives. It first aims to present Murdoch as an imaginative philosopher by exploring the role of literature in her philosophical writing. In doing so, it challenges various presuppositions about philosophy, held by both philosophers and non-philosophers. Its second aims is to reconsider these assumptions in general terms. This part draws significantly on the work of Le Doeuff. In particular, it considers the presence of imagery in philosophy as well as philosophy’s assumed neutrality, which has arisen from its long affiliation with science. Thirdly, the thesis presents a reconsideration of the notion of imagination. This notion is often involved in the interdisciplinary debate between theology, philosophy and the arts. Murdoch’s notion of imagination challenges two important assumptions. By releasing imagination from the limited corner of art, it first challenges a strict distinction between literary and systematic writing. By introducing fantasy as the bad opposite of good imagination, it secondly critically assesses unconditional ‘praises of imagination’.

This thesis explores the relationship between social and individual forms of ordering social life on one hand, and the emergence of a number of ‘spheres’ of disorder in the experience of life on the other. In modern society such evidence of disorder can only be characterised in terms that reinforce the negative or formless experience of the human confrontations with disorder. Manifestations of radical contingency (taken as the cognitive residue of such disorder) in experience are thus contrasted with the progress and limits of reason and desire (which create the ‘valuable’ part of life), and these are further examined within a language of being that establishes the discordant nature of the relationship. It is argued that reason and desire, in creating value, always construct an edifice of social and personal expectation that is justified on the basis of the reliability of causal relations between phenomena in lived experience, and in so doing ‘make’ an objective and orderly social world. Several notions central to an understanding of the accumulation of categories of being in modern society are examined as the positive expression of the conditions of autonomous action, and thus as crucial determinants of value and identity. The central relationship is further investigated through the elaboration of three negative categories of experience, which are seen to contain individual and social forms of action that forcefully remove, or contradict order and autonomous freedom as it is here defined. The thesis is therefore divided into three parts. Part 1 examines the loss of autonomy through gambling, and specifically through the singular experience of the wager, which is seen to be an intensification of the motion that constitutes life, but that boldly refuses to be contained, as rational autonomy would dictate. Part 2 deals with the atomisation of knowledge and experience in modern society, looking specifically at instances of ‘non-representational’ art of the twentieth century as the residue of developments that had as a positive aim the refinement of experience. Part 3 deals with the material exclusion of various kinds of garbage resulting from both social and technological progress, and from the emergence of a multiplicity of opportunities for the establishment of self-identity that are seen as both a product of dividing the world of experience into ever smaller categories (i.e., the refinement of the ‘objective’ world) and of the subjective relationship between the individual in modern society and the world of objects.

Though Dante never read Plato's dialogues on love, when examining the texts of Dante one notes the presence of Platonic thought and influence particularly concerning the notion of love. This thesis will focus upon the Platonic notion of eros and how it changes over time, ultimately being integrated into the Christian notion of love as understood by Dante, and how this Platonic influence is instantiated within Dante's poetry. The inherent ambiguity of the concept of love, evident historically through frequent debates concerning its value whether positive, negative or in-between, makes any investigation into the nature of love problematic, often aporetic. One aim of this thesis is to help overcome some of the aporiai of knowledge concerning love through focusing upon one form of love, eros or passionate desire, which we shall use in order to understand love more generally through exploring its points of intersection and overlapping with certain other types of love, each of which emphasizes different aspects of love's character differentiated through culture and period. Significantly eros, as perhaps the most ambiguous type of love, is often characterized negatively. Taking into account Nygren's negative view of eros which he sees as being wholly acquisitive and self-seeking as opposed to the thoroughly selfless Christian agape, we shall consider whether this view tells the full truth about eros. In this endeavour we shall explore the interrelationship of eros and understanding understood as a dialectic directed towards the pursuit of truth, which in both the Platonic and Christian traditions involves the permanent possession of the good, beautiful and true; these converge in Neo-Platonic tradition, forming a unity which in Christianity is identified with God. We shall also explore how various strands of eros relate to and articulate the notion of love of the individual. These explorations cast light on the transformation of Platonic eros by Christian agape into the Latin concept of caritas. In terms of procedure, we shall examine the notion of Platonic eros as presented in the Symposium and the Phaedrus and how this conception is reinterpreted in Dante's Commedia, these texts together acting as a lens which -will enable us better to comprehend the significance of Bros, and of love more generally, through the transformation of eros over time.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Le Modèle Standard de la physique des particules décrit les particules elementaires et leurs interactions avec une grande précision. Il décrit trois des quatre interactions fondamentales connues entre les particules elementaires : les interactions faibles, fortes et électromagnétiques. Le Modèle standard fournit aussi une description précise des interactions électrofaibles jusqu’à des échelles d’énergie qui ont été étudies dans les expériences de physique de haute énergie. Les interactions ainsi que les désintégrations d'un grand nombre de particules découvert et observe tout au long des expériences différentes dans les 50 dernières années sont également décrites. En dépit de son succès, le Modèle Standard est loin d’être une théorie complète des interactions fondamentales car il n’intègre pas la théorie complète de la gravitation telle que décrite par la relativité générale, ni la prédiction de l’accélération de l'expansion de l'univers (qui pourrait être décrite par l’énergie noire). La théorie ne contient aucune particule de matière noire viable qui possède toutes les propriétés déduites de la cosmologie observationnelle. Également, elle ne prend pas en compte les oscillations de neutrinos (et leurs masses non nulles). On pense que la nouvelle physique doit exister conduisant a de nouvelles particules et phénomènes. L’échelle a laquelle cette nouvelle physique devrait apparaıtre n'est pas bien connue, cependant plusieurs arguments soulignent l’échelle du TeV et nécessitent une très haute énergie et des puissants collisionneurs de hadrons. Le Large Hadron Collider (LHC) est le plus grand accélérateur et collisionneur de particules existant. / The Standard Model of particle physics is very successful in describing elementary particles and their interactions with a great precision. It describes three of the four known fundamental interactions between elementary particles : the weak, the strong and the electromagnetic interactions. The Standard Model also provides an accurate description of the electroweak interactions up to energy scales that have been explored in high energy physics experiments. The interaction and decay of a large number of particles discovered and observed throughout different experiments in the last 50 years are also described. Despite its great success, the Standard Model falls short of being a complete theory of fundamental interactions because it does not incorporate the full theory of gravitation as described by general relativity, or predict the accelerating expansion of the universe (as possibly described by dark energy). The theory does not contain any viable dark matter particle that possesses all of the required properties deduced from observational cosmology. It also does not account for neutrino oscillations (and their non-zero masses). It is thought that new physics should exist leading to new particles and phenomena. The scale at which this new physics should appear is not well known, though several arguments point to the TeV scale and require a very high energy and powerful hadron collider. The Large Hadron Collider (LHC) is the biggest existing particle accelerator and collider. It is designed to provide proton-proton collisions with an unprecedented center-of-mass energy of 14 TeV, with instantaneous luminosities up to 10^{34} cm−2s−1.

p53 is a critical tumour suppressor which acts to repair or remove abnormal cells and thus prevent cancer. Aberrant function of p53 is therefore a critical step in tumourigenesis and p53 is mutated in half of all cancers. Mutation of p53 leads to both a loss of normal wildtype function as well as the gain of oncogenic function. p53 is considered to be a promising therapeutic target and therapeutic strategies for targeting of the p53 pathway include: 1. Activation of wild-type p53 (wtp53) protein function, 2. Refolding of mutant p53 (mtp53) into the wtp53 conformation, 3. Reduction of mtp53 protein levels. In this work a number of small molecule screening assays were used to identify potentially novel regulators of both wtp53 and mtp53. Screening of a protein kinase inhibitor library for small molecules which can stimulate wtp53 activity identified the GSK3 pathway and a CDK pathway as dominant suppressors of wtp53 function. Screening of the library for inhibitors which reduce mtp53 protein levels led to the identification of two IKKβ inhibitors. The work then focused on investigating the effects of one of these compounds, IMD0354, on the mutant p53 pathway; with a specific focus on MDM2 as the most rapidly responding biomarker. IMD0354 is a well characterised inhibitor which has been shown to specifically inhibit IKKβ leading to the repression of the Nf-κB pathway. This study shows that IKKβ inhibition leads to the loss of a number of oncogenic proteins including mtp53, MDM2 and cyclin D. Mass-spectrometry based (ITRAQ) proteomic analysis was then employed to identify potential mediators and/or co-regulated factors in response to IKKβ-inhibition via IMD0354 treatment. This led to the identification of RPS3 as a potential negative regulator of MDM2 protein expression; the reduction in MDM2 protein in response to IMD0354 treatment is shown to be partially dependent on RPS3. Together this data has identified, using small molecule kinase inhibitor libraries: (i) dominant kinase signalling pathways that suppress wt-p53 and (ii) a dominant kinase signalling pathway that sustains expression of mutant p53 and MDM2 in cancer cell lines. This latter data supports further investigation to aid understanding of how the IKK signalling pathway cross-talks to the p53-MDM2 axis.

M.A. (African Languages) / Please refer to full text to view abstract