Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Les espèces de Plasmodium induisent une réponse immunitaire spécifique, qui stimulent la libération de cytokines et entraînent des réponses protectrices ou pathologique. Dans les modèles murins, ses réponses dépendent des combinaisons de la souche de souris et de l’espèce Plasmodium utilisés. Les souris C57BL/6 infectées, avec un nombre relativement faible de Plasmodium chabaudi AS, expérimentent une infection qui n’est pas fatale et une résistance à l'infection associée avec une réponse inflammatoire forte qui implique l'interleukine-12 et l'activation précoce des cellules T CD4+ avec une production élevée de IFN-γ et TNF-α. Cette réponse pro inflammatoire est par la suite contrôlée par l'IL-10 qui mène au contrôle et à la résolution de l'infection. Cependant, les souris qui succombent à l’infection développent la parasitémie fulminante et une infection mortelle. La cause des différences de résolution n'est pas bien comprise, bien que les principaux composants de protection et les réponses immunitaires pathologiques sont bien connus. Cette étude utilise le modèle de Plasmodium chabaudi dans le souris C57BL/6, pour: 1) comparer la résolution de l'infection et de la pathologie entre le P. chabaudi AS qui est relativement non virulentes et la plus virulentes de P. chabaudi CB; 2) déterminer si les différences dans la réplication des parasites, charge parasitaire ou les réponses immunitaire de l'hôte contribuent a des différences pathologiques; 3) ) chercher à déterminer ce qui mène les différences dans la réponse immunitaire de l'hôte. P. chabaudi CB provoque une infection plus sévère chez les souris C57BL/6 par rapport à P. chabaudi AS, avec une mortalité de ±40% endéans 12 jours et une moyenne des pics de 50% par rapport à 30% observé dans des souris infectées avec P. chabaudi AS. Aucune différence n’a été observé entre la charge corporelle des parasites durant les infections de P. chabaudi AS comparée a celle de P. chabaudi CB. Un taux élevé de cellules NK a été constaté dans les rate des souris infectées par P. chabaudi AS au niveau maximum de parasitémie, tandis que le taux des cellules NK dans les rates des souris infectées par P. chabaudi CB est resté constant tout au long de l'infection. Par conséquent, la poussée du taux des cellules NK contribue a l’infection non virulente des clones P. chabaudi AS. Ceci est du à la capacité cytolytique des cellules NK ainsi qu’à la production des IFN- γ. Le nombre de lymphocytes T CD4+ présents dans les rates des souris C57BL/6 infectées par P. chabaudi CB était inférieur a celui des lymphocytes T CD4+ présent dans les rates des souris infectées par P. chabaudi AS ; 1 fois moins de cellules T CD4+l'IFN-γ+ et 2 fois moins de cellules l'IL-10 +T CD4+ ont été observés. Une analyse plus approfondie a illustré que les cellules l'IL-10+ IFN-γ+ T CD4+ sont plus fréquentes chez les souris infectées par P. chabaudi AS. L'absence des cellules d'IL-10+ IFN-γ+ T CD4+ chez les souris infectées par P. chabaudi CB contribue à la pathologie, parce que ces cellules limitent les réactions inflammatoires mortelles et améliorent la perte de poids, l'hypothermie et l'anémie, en régulant l'immunopathologie. Les différences observées dans les réponses immunitaires ne sont pas contrôlées par l'interaction des parasites spécifiques tel que glycophosphatidylinositol avec TLR2, mais plutôt par l'IFN-α/β. Bien qu’ IFN-α/β n’ont pas été détecté dans le plasma, des niveaux plus élevés d'IFN-α/β d'ARNm transcrits ont été trouvés dans la rate de C57BL/6 infectées par P. chabaudi CB au cinquième jour d’infection. Le manque d’IFN-α/βR limite la pathologie et l’infection P. chabaudi CB virulentes sans affecter les infections P. chabaudi AS non virulentes. / Plasmodium species induces a specific immune response, stimulating the release of cytokines, resulting in either protective or pathological responses. In mouse models, this is depended on mouse strain or parasite combination used. C57BL/6 infected with relatively low numbers of Plasmodium chabaudi AS pRBC experience a non-lethal infection and resistance is associated with robust inflammatory responses that involves IL-12, early activation of CD4+Th1 cells with production of high levels of IFN-γ and TNF-α, this pro-inflammatory response is subsequently controlled by IL-10 leading to control and resolution of infection. However, mice that succumb to infection develop fulminant parasitaemia and increase mortality. The cause of the differences in infection outcome is not well understood, although the principal components of protective and pathological immune responses are well known. Using the model of Plasmodium chabaudi in C57BL/6, this study addresses the following; 1) compares the course of infection and pathology between the relatively avirulent P. chabaudi AS and the more virulent P. chabaudi CB; 2) investigates whether differences in parasite replication, parasite load or host immune responses contribute to differences in pathology; 3) what mediates the differences in host immune response? P. chabaudi CB causes a more severe infection in C57BL/6 compared to P. chabaudi AS, with ±40% mortality within 12 days and mean peak parasitaemia of 50% compared to 30% in P. chabaudi AS infected mice. There was no difference in total body parasite load between the P. chabaudi AS and CB infections. A High number of NK cells was found in the spleen of P. chabaudi AS infected mice at peak parasitaemia, whereas NK cells numbers in spleen of P. chabaudi CB infected mice remained constant throughout infection. Hence, the elevated NK cells contribute to parasite clearance in the avirulent P. chabaudi AS clone, because of its IFN-γ production and cytolytic activity. P. chabaudi CB infected C57BL/6 were found to have reduced number of CD4+T cells in the spleen, with 1-fold decrease in IFN-γ+CD4+T cells and 2-fold decrease in IL-10+ CD4+T cells when compared to CD4+T cells from P. chabaudi AS infected mice. Further analysis showed that IL-10+IFN-γ+CD4+T cells were more prevalent in P. chabaudi AS infected mice. The absence of IL-10+IFN-γ+CD4+T cells in P. chabaudi CB infected C57BL/6 contributes to pathology, because these cells limit lethal inflammatory responses and ameliorate weight loss, hypothermia and anemia, by regulating immunopathology. The differences observed in immune responses are not mediated by interaction of parasite specific GPIs with TLR2, but rather by IFN-α/β. Although IFN-α/β were not detected in plasma, higher levels of IFN-α/β mRNA transcripts were found in the spleen of P. chabaudi CB infected C57BL/6 on day 5. IFN-α/βR deficiency limits virulent P. chabaudi CB infections with no effect on avirulent P. chabaudi AS infections.

A 3,4-metilenodioximetanfetamina (MDMA) é a principal substância psicoativa comercializada ilegalmente em comprimidos de ecstasy. O MDMA é uma droga de ação psicotrópica e uso proscrito, conforme lista F (grupo F2) da ANVISA, pois apresenta propriedades alucinógenas e estimulantes e seu uso/abuso pode gerar uma série de danos à saúde dos usuários. O desenvolvimento de eletrodos quimicamente modificados (EQMs) na eletroanalítica tem por finalidade a obtenção de sistemas de detecção mais sensíveis e seletivos para o analito de interesse. Também, considera-se necessário desenvolver novas técnicas e métodos para a detecção de compostos em amostras de interesse forense, a fim de obter ferramentas para auxiliar os cientistas forenses no combate ao comércio ilícito de substâncias. Conforme problemática exposta, este trabalho teve por finalidade o desenvolvimento de eletrodos quimicamente modificados utilizando como modificadores da superfície eletródica de carbono vítreo o Nafion e Nafion/CB[7], utilizando deposição por drop coating e spin coating para a detecção de MDMA através das técnicas de voltametria cíclica e onda quadrada. Conforme o sistema empregado, os melhores EQMs desenvolvidos foram de Nafion (1,5% v/v) e Nafion (1,5% v/v)/CB[7] (10,0 µg.mL-1). Os EQMs desenvolvidos apresentaram limite de detecção e quantificação na faixa de traços e menores que aqueles reportados em outros trabalhos da literatura. Considerando a aplicação dos EQMs para a detecção de MDMA em amostras de ecstasy, verificaram-se as respostas voltamétricas de outras substâncias: cafeína, metanfetamina, teobromina, lidocaína, cloridrato de procaína, (±)-metanfetamina e cloridrato de cocaína. Nas condições experimentais empregadas, observou-se que as substâncias estudadas não atuam como falsos positivos para o MDMA. Paralelamente, obtiveram-se onze lotes de comprimidos de ecstasy (apreendidos e cedidos pela Polícia técnico-científica de Ribeirão Preto-SP) e realizaram-se análises qualitativas e quantitativas nos mesmos, utilizando técnicas colorimétricas (Marquis, Ácido sulfúrico, Simon e Simon com acetona) e cromatográficas (CG-EM E CLAE-EM). Considerando o melhor EQM desenvolvido, quantificaram-se 11 lotes de ecstasy pela técnica voltamétrica e cromatográfica, dentre os lotes estudados, dois não continham MDMA, um apresentou uma mistura de MDMA e cafeína e os demais continham MDMA. A concentração de MDMA presente nos lotes variou de 0 até 61 % em massa. A detecção de MDMA em ecstasy pelo método voltamétrico desenvolvido se mostrou viável e sensível para o analito de interesse. / The 3,4-methylenedioxymethamphetamine (MDMA) is the main psychoactive component of ecstasy tablets, that have an illicit trade. MDMA has been an illicit psychotropic drug, and it has a prohibited use (group F2, in ANVISAs F list), because of its hallucinogenic and stimulating effects, and the use/abuse can poses serials health risks. The development of chemically modified electrodes (CME) in electroanalytical methods aims to get more sensitive and selective systems to detect the analytes. In this context, it is necessary to develop new techniques and methodologies to the detection of illicit samples; it provides more tools to help the forensic scientists to combat the illicit drug trade. So, this work focused in the development of chemically modified electrodes (CMEs) with modifications on the glassy carbon surface by drop coating and spin coating using Nafion and Nafion/CB[7] solutions. The CMEs were tested using cyclic, and square wave voltammetry to detect MDMA. Considering the employed system, the best CMEs were made by Nafion (1.5% v/v), and Nafion (1.5% v/v)/CB[7] (10.0 µg.mL-1) thin films. It was possible to observe better sensitivities for these sensors, in comparison to other MDMA studies reported in the literature. The specificity of the proposed sensors was checked in relation to other drugs: caffeine, methamphetamine, theobromine, lidocaine, procaine hydrochloride, and cocaine hydrochloride. These drugs do not interfere in this voltammetric method. Additionally, we studied eleven lots of ecstasy samples, allowed by the Scientific Police - Ribeirão Preto-SP, and we provide qualitative and quantitative studies using colorimetric techniques (Marquis, Sulfuric acid, Simon, and Simon with acetone), and chromatografic techniques (GC-MS and HPLC-MS). The MDMA quantification in real samples was obtained by high performance liquid chromatography with a mass spectrophotometer, and we compared with the voltammetric technique, using the developed CME. Between the analyzed lots, two of them didnt present in their composition, one lot had a mix of caffeine and MDMA, and another presented MDMA. The MDMAs concentration in lots had a large variation, with 0 to 61 % w/w. The MDMAs voltammetric detection in ecstasy lots was viable. And, it is also possible to apply this methodology to analyze MDMA traces.

A 3,4-metilenodioximetanfetamina (MDMA) é a principal substância psicoativa comercializada ilegalmente em comprimidos de ecstasy. O MDMA é uma droga de ação psicotrópica e uso proscrito, conforme lista F (grupo F2) da ANVISA, pois apresenta propriedades alucinógenas e estimulantes e seu uso/abuso pode gerar uma série de danos à saúde dos usuários. O desenvolvimento de eletrodos quimicamente modificados (EQMs) na eletroanalítica tem por finalidade a obtenção de sistemas de detecção mais sensíveis e seletivos para o analito de interesse. Também, considera-se necessário desenvolver novas técnicas e métodos para a detecção de compostos em amostras de interesse forense, a fim de obter ferramentas para auxiliar os cientistas forenses no combate ao comércio ilícito de substâncias. Conforme problemática exposta, este trabalho teve por finalidade o desenvolvimento de eletrodos quimicamente modificados utilizando como modificadores da superfície eletródica de carbono vítreo o Nafion e Nafion/CB[7], utilizando deposição por drop coating e spin coating para a detecção de MDMA através das técnicas de voltametria cíclica e onda quadrada. Conforme o sistema empregado, os melhores EQMs desenvolvidos foram de Nafion (1,5% v/v) e Nafion (1,5% v/v)/CB[7] (10,0 µg.mL-1). Os EQMs desenvolvidos apresentaram limite de detecção e quantificação na faixa de traços e menores que aqueles reportados em outros trabalhos da literatura. Considerando a aplicação dos EQMs para a detecção de MDMA em amostras de ecstasy, verificaram-se as respostas voltamétricas de outras substâncias: cafeína, metanfetamina, teobromina, lidocaína, cloridrato de procaína, (±)-metanfetamina e cloridrato de cocaína. Nas condições experimentais empregadas, observou-se que as substâncias estudadas não atuam como falsos positivos para o MDMA. Paralelamente, obtiveram-se onze lotes de comprimidos de ecstasy (apreendidos e cedidos pela Polícia técnico-científica de Ribeirão Preto-SP) e realizaram-se análises qualitativas e quantitativas nos mesmos, utilizando técnicas colorimétricas (Marquis, Ácido sulfúrico, Simon e Simon com acetona) e cromatográficas (CG-EM E CLAE-EM). Considerando o melhor EQM desenvolvido, quantificaram-se 11 lotes de ecstasy pela técnica voltamétrica e cromatográfica, dentre os lotes estudados, dois não continham MDMA, um apresentou uma mistura de MDMA e cafeína e os demais continham MDMA. A concentração de MDMA presente nos lotes variou de 0 até 61 % em massa. A detecção de MDMA em ecstasy pelo método voltamétrico desenvolvido se mostrou viável e sensível para o analito de interesse. / The 3,4-methylenedioxymethamphetamine (MDMA) is the main psychoactive component of ecstasy tablets, that have an illicit trade. MDMA has been an illicit psychotropic drug, and it has a prohibited use (group F2, in ANVISAs F list), because of its hallucinogenic and stimulating effects, and the use/abuse can poses serials health risks. The development of chemically modified electrodes (CME) in electroanalytical methods aims to get more sensitive and selective systems to detect the analytes. In this context, it is necessary to develop new techniques and methodologies to the detection of illicit samples; it provides more tools to help the forensic scientists to combat the illicit drug trade. So, this work focused in the development of chemically modified electrodes (CMEs) with modifications on the glassy carbon surface by drop coating and spin coating using Nafion and Nafion/CB[7] solutions. The CMEs were tested using cyclic, and square wave voltammetry to detect MDMA. Considering the employed system, the best CMEs were made by Nafion (1.5% v/v), and Nafion (1.5% v/v)/CB[7] (10.0 µg.mL-1) thin films. It was possible to observe better sensitivities for these sensors, in comparison to other MDMA studies reported in the literature. The specificity of the proposed sensors was checked in relation to other drugs: caffeine, methamphetamine, theobromine, lidocaine, procaine hydrochloride, and cocaine hydrochloride. These drugs do not interfere in this voltammetric method. Additionally, we studied eleven lots of ecstasy samples, allowed by the Scientific Police - Ribeirão Preto-SP, and we provide qualitative and quantitative studies using colorimetric techniques (Marquis, Sulfuric acid, Simon, and Simon with acetone), and chromatografic techniques (GC-MS and HPLC-MS). The MDMA quantification in real samples was obtained by high performance liquid chromatography with a mass spectrophotometer, and we compared with the voltammetric technique, using the developed CME. Between the analyzed lots, two of them didnt present in their composition, one lot had a mix of caffeine and MDMA, and another presented MDMA. The MDMAs concentration in lots had a large variation, with 0 to 61 % w/w. The MDMAs voltammetric detection in ecstasy lots was viable. And, it is also possible to apply this methodology to analyze MDMA traces.

No description available.

This thesis explores issues surrounding Barbadian cultural identity in the post-colonial period. Emphasis is placed on the role of history in constructing cultural identity. Beginning with the debate involving the Lord Nelson statue which stands in the capital of Barbados, the question of negotiating post-colonial space is closely examined in the three case studies that form the body of the research. These are based on evidence gathered from both archival and secondary sources, as well as personal interviews. The case studies review the following: the history of the usage of the 'Little England' motto and its renewed use in the post-colonial period; the historical development of the community group known as the Landship, whose trademark is to wear naval livery and dance their naval manoeuvres during their parades; the history of the Harvest Home/Crop Over festival of the slavery and post-slavery periods, as well as the history of the modern street festival that it has become. The thesis argues that elements of the colonial discourse gain new life in the post-colonial period because of the struggle between the colonial narrative of History and the emerging new histories. It proposes that in this Barbados example, the performance culture has provided new grounds for advancing the process of decolonisation.

The purpose of this thesis is to provide a thematic analysis of the historical, political, and economic context of Seleucid portraiture, namely that on coins, but with reference to gemstones, seals, and sculpture where evidence exists. No attention has been given to the aesthetic value of such items, as has been the habit of art historians, as a great deal of the evidence analysed here consists of bronze coins. Nor is this work intended to be a catalogue, as technical information on coins has been well documented in the many catalogues in this field. The first chapter provides a general survey of the issue of autonomy and its relationship to the Seleucids, whether among the Greek poleis of Asia Minor or other autonomous areas of the Seleucid empire. This is followed by an obligatory discussion of the influence of Alexander on the Seleucids, which has been kept deliberately short due to the amount of scholarship already completed in this field. The issue of warfare and its effect on Seleucid iconography follows this. The first three chapters cover issues affecting Seleucid iconography, whether for legitimate kings or otherwise, which leads on to a chapter covering the Seleucid usurpers. The function of this chapter within the thesis is twofold; firstly, it introduces the concept of usurpation and its effect on the iconography of legitimate kings; secondly, it contains extensive discussion of the coinages of the individual usurpers. The next four chapters serve to analyse the variation of the royal image for legitimate kings, assessing the effect of autonomy, warfare, Alexander, and usurpation on the changing royal image. The kings discussed in the respective chapters were chosen on similarities of iconography and factors affecting this. The final chapter is a discussion on Seleucid female iconography, affected by many of the same factors as male portraiture.

This thesis investigates the role of arts practitioners in cultural policy activity, both as a general concern for cultural policy studies and in the specific arena of post-war cultural policy in Britain. In so doing it challenges a common perception that arts practitioners have no such involvement, and seeks to discover the extent and form of their activity. it explores the history of practitioners’ participation in cultural policy formation and implementation; what obstacles they have faced and how their involvement could be better facilitated; and, importantly, why it matters whether they are involved. These issues have remained largely unrecognised among cultural policy researchers. Part II of the thesis examines the subject through a case study of new playwriting policy in England. Drawing on unpublished primary documents, interviews, and observation, it pays particular attention to playwrights’ organisations and their history of self-directed activity. These organisations and other agencies concerned with theatre writing are embedded in networks which cross the boundaries of policy and creative practice. The thesis argues that arts practitioners can enhance their place in the policy process through their own actions, and that participation in these networks increases their opportunity for policy input and influence. Of key importance is the question as to why the involvement of practitioners in cultural policy activity is of any significance. The thesis puts forward the view that arts practitioners and their organisations can be seen as part of the fabric of civil society, and their participation in policy activity as contributing to the maintenance and enlargement of democratic life. It is, then, not a marginal issue, nor of concern to the arts alone, but integral to a wider debate about sustaining democratic engagement and the civic arena in the twenty-first century.

Scholarly interest in travel literature has increased substantially in recent years. However, there has been a lack of sustained, cohesive commentary on the journey motif in German Romantic culture, particularly its origins and manifestations in literature and philosophy. My doctoral research fills this gap through a philosophically- and historically-informed reading of German Romanticism. The thesis examines 1) the paradigmatic template of the literary journey established by Goethe in Wilhelm Meisters Lehrjahre, 2) metaphors of movement and mobility within the Idealist philosophy of Kant and Fichte and their role, 3) the manner in which these metaphors migrate into the theoretical and prose writings of Novalis, 4) Tieck’s notion of the sublime and its relevance for the Romantic journey, and 5) the late Romantic satirization of the journey motif within Eichendorff’s prose. Additionally, the thesis serves to show how philosophical discourse of the Enlightenment had reached something of an impasse in its use of the journey motif, with the subject unable to evolve and renew itself beyond the strictures of particular models of subjective cognition. The Romantics thought literary practice was to supersede philosophy and it was mobility in the form of the journey as both metaphor and process, which helped bring about this transition and created a flexible self-authoring and self- renewing model of the subject. The study also recounts a particular history of Romanticism which charts, via the history of the journey, the movement’s youthful idealism, the fear of the pitfalls of human subjectivity, and its eventual self-distanciation through parody.

This thesis will argue that the contemporary educational system of Cyprus denies young people opportunities to participate in the creation of their culture, which can provide the nest for the exploration and understanding of their individual and collective lives. Culture, in schools, is treated not as a dynamic process in which the young people can play the main role but instead as a static field of knowledge that should be studied and learnt. This approach, however, contradicts the same principles that were the foundations of the ancient culture that the young Greeks have inherited from the past whose performative and participatory nature ascribed to it a proactive and democratic public life that guaranteed everyone the right to speak and act. This thesis argues that the Greek young people of contemporary Cyprus should be entitled to participation in recreating and reconstructing the meanings and values of those stories that have inherited from the past and that bind them together as one people in ways that help them make sense of their contemporary private and public roles. The thesis argues that the myths of the past should be reinterpreted and repositioned again in the present to respond to the immediate social context of the young people in a participatory and democratic way so as to enable a progress of this culture and a connection between the past, the present and the future. The thesis shows that culture is under continuous reconstruction taking on the example of fifth century BC Athens where theatre and public life fed one another and developed to respond to the current socio-historical context of the time. Throughout, the thesis shows in what ways theatre can provide the means for the investigation of the inherent meanings in the myths of the past and also its significance in playing the role of the social agent that can enable transformation and progress. The thesis consists of an introduction, eight chapters and a conclusion. In the Introduction I identify the problem that exists in the contemporary educational system of Cyprus concerning the way that the field of culture is approached and present the conceptual framework that provides the foundation for proposing a new Theatre of Myth. Chapter one provides a critical reflection on and analysis of the oral culture of Homer to the democratic fifth century BC Athens and the birth of tragedy. Chapter two studies, both from the ideal and the material aspect, the social role of the Athenian tragic theatre and its polis during the fifth century. Chapter three seeks to base the arguments made in the thesis of the educational and political role of the fifth century theatre through a critical analysis of its form and content. Chapter four identifies and supports the principles of the proposed Theatre of Myth, drawing from the twentieth century developments in Modem Drama whilst chapter five shows how the Drama-in-Education tradition attempts to bridge the practices in the Modem Drama paradigm to come closer to the proposed theatre model. Chapter six provides the methodology followed for a pilot case study that attempts to transfer the Theatre of Myth into practice, which is the preoccupation of chapter seven. Chapter eight discusses and analyses the findings of the case study to inform the theoretical lines of the model of the Theatre of Myth. Some conclusions are discussed concerning the potential and the limitations of the Theatre of Myth in the end of the thesis.