4 resultados para Elizalde, Silvia

em CORA - Cork Open Research Archive - University College Cork - Ireland


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This dissertation assesses from an under-explored angle the enduring contention over Travellers’ ethnic recognition in the Republic of Ireland, particularly over the last decade. The novelty of this study concerns not only its specific focus on and engagement with the debate on ‘Traveller ethnicity’ among Traveller activists. It also pertains to the examination of Travellers’ arguments for and against ethnicity in light of critical theorisations as well as insights from identity politics. Furthermore, the adoption of a Critical Discourse Analytical framework offers new perspectives to this controversy and its potential implications. Finally, this thesis’ relevance extends beyond the contention on ‘Traveller ethnicity’ in itself. It also draws attention to the complex dynamics of colonisation and appropriation between the global and the local. Particularly, it points to the interplay between international human rights discourses and the local ones, formulated by NGOs struggling for equality. In this way it sheds light on more general issues such as the dialectical potential of human rights discourses: the benefits and pitfalls of framing recognition claims in the legalistic terms of human rights. In this study it is argued that the contention on ‘Traveller ethnicity’ defies a simplistic polarisation between Irish Travellers and the Irish State since it has been simultaneously played out within the Travelling community. Specifically, this study explores how ‘Traveller ethnicity’ has been introduced, embraced, promoted and contested within Traveller politics to the point of becoming a hotly debated and divisive issue among Traveller activists and at the heart of the community itself. Putting Traveller activists centre-stage, their discourses for and against ‘Traveller ethnicity’ are examined and assessed against one another and their potential implications for Traveller politics, policies and identities are pointed out. Contending discourses are historically contextualised as the product of specific structural, material and discursive configurations of power and socio-economic relations within Irish society. Discourses for and against ‘Traveller ethnicity’ are assessed as being significant beyond the representational level. They are regarded as contributing to dialectically constitute Travellers’ ways of being, representing and acting. Furthermore these discourses are considered as sites and means of power struggles, whose stakes are not only words, but relate to issues of power and leadership within the Travelling community; adjudications over material resources; the adoption of certain policy approaches over others; and, finally, the consolidation of certain subject positions over others for Travellers to draw upon and relate to mainstream society. This study highlights an ongoing ideological struggle for the naturalisation of ‘Traveller ethnicity’ as a self-evident ‘fact’, which involves no active choice by Travellers themselves. Overall, ‘Traveller ethnicity’ appears to constitute an enduring source of dilemmas for the Travelling community. These revolve around the contradictory potential of ethnicity claims-making —both its perils and advantages— and its status as a potent political strategic resource that can both challenge and reinforce existing power relations, policies and identities.

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Inflammatory bowel diseases (IBD), encompasses a range of chronic, immune-mediated inflammatory disorders that are usually classified under two major relapsing conditions, Crohn’s Disease (CD) and ulcerative colitis (UC). Extensive studies in the last decades have suggested that the etiology of IBD involves environmental and genetic factors that lead to dysfunction of epithelial barrier with consequent deregulation of the mucosal immune system and inadequate responses to gut microbiota.Over the last decade, the microbial species that has attracted the most attention, with respect to CD etiology, is Eschericia coli. In CD tissue, E. coli antigens have also been identified in macrophages within the lamina propria, granulomas, and in the germinal centres of mesenteric lymph nodes of patients. They have been shown to adhere to and invade intestinal epithelial cells whilst also being able to extensively replicate within macrophages. Through the work of genome-wide association studies (GWAS), there is growing evidence to suggest that the microbial imbalance between commensal and pathogenic bacteria in the gut is aided by a defect in the innate immune system. Autophagy represents a recently investigated pathway that is believed to contribute to the pathogenesis of CD, with studies identified a variant of the autophagy gene, ATG16L1, as a susceptibility gene. The aim of my thesis was to study the cellular and molecular mechanism promoted by E.coli strains in epithelial cells and to assess their contribution to IBD pathology. To achieve this we focused on developing both an in vitro and in vivo model of AIEC infection. This allowed us to further our knowledge on possible mechanisms utilised by AIEC that promoted their survival, as well as developing a better understanding of host reactions. We demonstrate a new survival mechanism promoted by E.coli HM605, whereby it induces the expression of the anti-apoptotic proteins Bcl-XL and BCL2, all of which is exacerbated in an autophagy deficient system. We have also demonstrated the presence of AIEC-induced inflammasome responses in epithelial cells which are exacerbated in an autophagy deficient system and expression of NOD-like receptors (NLRs) which might mediate inflammasome responses in vivo. Finally, we used the Citrobacter rodentium model of infectious colitis to identify Pellino3 as an important mediator in the NOD2 pathway and regulator of intestinal inflammation. In summary, we have developed robust and versatile models of AIEC infection as well as provide new insights into AIEC mediated survival pathways. The collected data provides a new perception into why AIEC bacteria are able to prosper in conditions associated with Crohn’s disease patients with a defect in autophagy.

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Cytokine-driven signalling shapes immune homeostasis and guides inflammatory responses mainly through induction of specific gene expression programmes both within and outside the immune cell compartment. These transcriptional outputs are often amplified via cytokine synergy, which sets a stimulatory threshold that safeguards from exacerbated inflammation and immunopathology. In this study, we investigated the molecular mechanisms underpinning synergy between two pivotal Th1 cytokines, IFN-γ and TNF-α, in human intestinal epithelial cells. These two proinflammatory mediators induce a unique state of signalling and transcriptional synergy implicated in processes such as antiviral and antitumour immunity, intestinal barrier and pancreatic β-cell dysfunction. Since its discovery more than 30 years ago, this biological phenomenon remains, however, only partially defined. Here, using a functional genomics approach including RNAi perturbation screens and small-molecule inhibitors, we identified two new regulators of IFN-γ/TNF-α-induced chemokine and antiviral gene and protein expression, a Bcl-2 protein BCL-G and a histone demethylase UTX. We also discovered that IFN-γ/TNF-α synergise to trigger a coordinated shutdown of major receptor tyrosine kinases expression in colon cancer cells. Together, these findings extend our current understanding of how IFN-γ/TNF-α synergy elicits qualitatively and quantitatively distinct outputs in the intestinal epithelium. Given the well-documented role of this synergistic state in immunopathology of various disorders, our results may help to inform the identification of high quality and biologically relevant druggable targets for diseases characterised by an IFN-γ/TNF-α high immune signature

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Process guidance supports users to increase their process model understanding, process execution effectiveness as well as efficiency, and process compliance performance. This paper presents a research in progress encompassing our ongoing DSR project on Process Guidance Systems and a field evaluation of the resulting artifact in cooperation with a company. Building on three theory-grounded design principles, a Process Guidance System artifact for the company’s IT service ticketing process is developed, deployed and used. Fol-lowing a multi-method approach, we plan to evaluate the artifact in a longitudinal field study. Thereby, we will not only gather self-reported but also real usage data. This article describes the development of the artifact and discusses an innovative evaluation approach.