RNA interference (RNAi) is a post transcriptional gene silencing mechanism that allows potent and specific silencing of cognate mRNA transcripts. Selective silencing can be used to dissect complex polygenic diseases, elucidate the function of known genes and provide a tool for genetic therapy. Its use in the case of dominant inherited disorders including disorders of the central nervous system, depends on its ability to confer single nucleotide discrimination between normal and mutant gene alleles. In this thesis the ability of RNAi effector molecules to provide single nucleotide specificity was examined by targeting two dominant inherited mutations of the acetylcholine receptor that cause slow-channel syndrome. Allele-specific silencing was achieved for one mutation. The other mutation was also silenced but not in an allele specific way despite employing known techniques for increasing single-nucleotide specificity. The model used in this thesis is the congenital myasthenia slow-channel syndrome. This is a dominant inherited disorder of the neuromuscular junction which is both well-characterised and more readily accessible compared to the central nervous system, thus provides a prototype for development of allele-specific RNAi therapeutics. Here we describe a new transgenic animal model of the slow-channel syndrome and show good representation of the human disorder. The need for defining the characteristics that determine the effectiveness and the specificity of RNAi effectors at single-nucleotide level, along with the future uses of the newly described animal model are discussed.

This thesis examines the role and relationship of standardization and advocacy in humanitarian aid planning processes within the emergent field of education and instability. Standardization refers to the aid industry’s increasing emphasis on establishing ‘universal’ principles and normative frameworks. Advocacy refers to transnational-policy-network activities that move forward the global standardization agenda. The study focuses on the purposes and practices of knowledge creation by an education-and-instability ‘epistemic community’: the Inter-Agency Network for Education in Emergencies (INEE). Drawing on global-level interviews with key figures, participant observations, and documentary analysis, the research explores how this epistemic community promotes its core tenets: that education is an inherent human right and that educational provision should be a frontline humanitarian response on par with food distribution and shelter construction. The thesis analyzes the consensus-making process that resulted in the publication of the 2004 INEE Minimum Standards handbook, the then-epitome of the epistemic community’s knowledge. Next, the thesis examines the local application and adaptation of such global standardization processes in post-conflict Uganda. The case study presents the relationships among international and local ‘development partner’ institutions concerned with educational planning as a complex and contradictory story of power dynamics and knowledge circulation. These ‘partnerships’ are characterized by a shared quest for adherence to the knowledge encapsulated within standardized global frameworks and their normative principles. For Ugandan institutions, fluency in this discourse is a powerful tool to appropriate for their own ends. For international institutions, the knowledge is at once a technical resource and a means to bring ever more stakeholders into the wider epistemic community concerned with humanitarian aid. I argue that, through judicious use of standardization and advocacy mechanisms, INEE seeks to legitimize the education sector’s existence within the humanitarian aid industry and expand support for (or ‘conversion’ to) the education-and-instability epistemic community’s core beliefs.

This dissertation focuses on international actors' response to the ethnic cleansing perpetrated during the 1992 – 1995 Bosnian War. The work illuminates the multilateral attempt to reverse one of the outcomes of ethnic cleansing following the war, through the return of displaced people. The policy emphasis on "re-mixing" people, interpreted through a strategy of minority returns, and supported and coordinated on an international scale, was unprecedented. This dissertation asks: why did powerful states and international organizations pursue a re-mixing policy as a response to ethnic cleansing in Bosnia? At first glance, the choice seems counterintuitive. The policy was expensive. Post-1989, the West no longer needed "to keep Yugoslavia afloat." Furthermore, reversal required a degree and duration of international involvement that, at the time, was thought to be politically, militarily, and financially impossible. There are two existing explanations for this surprising phenomenon: international moralism and norm evolutionism. International moralists posit that international actors were moved to re-mix Bosnians out of a sense of guilt. Norm evolutionists argue that international norms governing appropriate responses to ethnic cleansing have shifted during the twentieth century towards support for re-mixing. In contrast to these two dominant views, this dissertation argues that the re-mixing policy initially emerged as a practical fix to a series of pressing, context-specific political challenges. State policymakers justified the re-mixing policy, however, on normative grounds. Though not the original incentive for action, international organizations on the ground then adopted the policy, empowered by states' normative justifications and thereby transformed the political rhetoric into concrete action. This dissertation corrects a common assumption that the origins and motivations behind the re-mixing policy were normative in nature, it contributes to a better understanding of how normative discourses emerge, mature, and transform into policy and it offers policy recommendations based on lessons learnt from this important and seemingly contradictory case.

T-lymphocytes are an essential cell type of the adaptive immune system. Due to their importance in immune responses and disorders, the molecular mechanisms leading to T-lymphocyte activation have been the subject of extensive research which has translated into important therapeutic developments. Early signalling events involving tyrosine phosphorylation are well characterised. However, later events involving other post-translational modifications are less well understood. Several studies have provided evidence suggesting a role for protein arginine methylation in T-lymphocyte activation. Arginine methylation is an essential post-translational modification in mammals and yet has not been extensively studied. No large scale analysis of arginine methylation sites has been performed. To gain insight into the role of protein arginine methylation in T-lymphocyte activation, the aims of this work were to: 1. Establish whether levels of arginine methylation are altered during Tlymphocyte activation 2. Use mass spectrometry based proteomics to identify arginine methylated proteins in the T-lymphocyte proteome 3. Further characterise an arginine methylated protein important to Tlymphocyte activation Arginine methylation was found to be induced after long term (>20 hours) stimulation of primary T-lymphocytes. Large increases in the main protein arginine methyltransferase, PRMT1, were also observed. Enrichment and labelling methods were developed to detect arginine methylated peptides from T-lymphocytes by mass spectrometry. This resulted in the identification of 265 unique arginine methylation sites in 141 proteins. 204 of the methylation sites were novel and 103 of the proteins had not previously been described as arginine methylated. Individual arginine methylation sites were characterised before and after activation of T-lymphocytes, with some sites showing significant changes in abundance. Among the novel arginine methylated proteins discovered were Dynamin II, WASp and WIPF1. These proteins are involved in re-organisation of the actin cytoskeleton at the immunological synapse formed between a Tlymphocyte and an antigen presenting cell. The functional consequences of the arginine methylation sites inWASp were characterised. WASp is essential for T-lymphocyte activation and some initial evidence showed that one of the arginine methylation sites is important for WASp activation.

Internally Displaced Persons ('IDPs') outnumber refugees by two to one and often have the same fears, needs and wants as refugees recognised as such under international law. However, refugee status entails international protection, while IDPs are left to the protection of their own state, which may, but by no means necessarily, be the very entity that has forced them to flee in the first place. In recent years, there have been significant developments in the realm of IDP protection. This includes the conclusion of two regional treaties on the protection of IDPs, the development of relevant soft law instruments, and the reformed 'Cluster Approach' of humanitarian response. Although the increased focus on IDP protection is a welcome development, the UNHCR has expressed the fear that 'activities for the internally displaced may be (mis)interpreted as obviating the need for international protection and asylum.' This thesis represents the first legal analysis of the relationship between the protection of IDPs and International Refugee Law. It will discuss five key challenges in this respect. First, the challenge of drawing the attention of the international community to the plight of IDPs; second, the challenge of developing an appropriate framework for the protection of IDPs; third, the challenge of ensuring that internal protection is not interpreted as a substitute for asylum; fourth; the challenge of determining the relationship between complementary protection and internal displacement; and fifth, the challenge of ensuring that IDP protection in an inter-agency context does not trigger the application of Article 1D of the Refugee Convention, rendering the Convention inapplicable to the recipients of that protection. This thesis will conclude by setting out the future challenges in the relationship between IDP protection and International Refugee Law, by identifying questions left open for further research, and by illustrating the overall impact and importance of this thesis' findings.

This thesis is about the depiction of the damaged male in contemporary American war films in the period 1990 to 2010. All the films in this thesis deploy complex strategies but induce simple and readily accessible pleasures in order to mask, disavow or displace the operations of US imperialism. It is my argument that the premier emotive trope for emblematising and offering up the damaged male as spectacle and political tool is the American war film. I also argue that masochistic subjectivity (and spectatorship) is exploited in these films, sometimes through using it as a radical transformative tool in order to uncover the contradictions and abuses in US imperial power, but mostly through utilizing its distinct narrative and aesthetic qualities in order to make available to spectators the pleasures of consuming these images, and also to portray the damaged male as a seductive and desirable subjectivity to adopt. The contemporary war film offers up fantasies of imperilled male psychologies and then projects these traumatic (or “weak”/“victimised”) states into the white domestic and suburban space of the US. Accordingly this enables identification with the damaged male, and all his attendant narratives of dispossession, innocence, and victimhood, and then doubles and reinforces this identification by threatening the sanctity and security of the US homeland. My argument builds towards addressing ethical questions of spectatorial passivity and culpability that surround our engagement with global media, and mass visual culture in the context of war. I ultimately identify ethical spectatorship of contemporary war films as bolstering a neo-liberal project advancing the “turn to the self”, and hence audiences could unwittingly be engaged in shoring up white male ethno-centricity and the attendant forces of US cultural and geopolitical imperialism.

Made available in DSpace on 2016-04-27T16:33:34Z (GMT). No. of bitstreams: 1 Valeria de Souza.pdf: 801488 bytes, checksum: d4a5310a9ca18f351e9f4858663c1e1c (MD5) Previous issue date: 2008-02-29 / Secretaria da Educação do Estado de São Paulo / This paper is focused on the role of the Technical-Pedagogic Assistant and the circumstances in which he works, it means, the Pedagogic Offices in the Regional Education Offices of São Paulo State and has as goals: a) to outline a profile of the Technical-Pedagogic Assistant and his work conditions; b) to identify his role in the educational system of São Paulo State; c) to provide a recapitulation of his field of activity on the basis of the files and official documents of the Pedagogic Offices in São Paulo State.The theoretical reference is concerned to in-service teacher training, as the focus of this work is the Technical-Pedagogic Assistant, who is responsible for the training of the teachers of the State Educational System. Hence, the reference support is provided by António Nóvoa, Gimeno Sacristán, Marcelo Garcia and Henry Giroux (for the conception of teacher training); Lawn & Ozga and Fernández Enguita (for the analysis of the process of teaching proletarianization) and finally Dubar (for the discussion of the formation of the professional identity). This is a quantitative and qualitative survey, encompassing an exploratory, analytical and descriptive study of the work conditions of the Technical-Pedagogic Assistant in the Secretariat of Education of São Paulo State which comprised: a) analysis of documents aimed to reconstitute the history of the Pedagogic Offices and a collection of information through an electronic form answered fully by 966 Technical-Pedagogic Assistants, between the years of 2006 and 2007; b) questionnaires answered by 20 of these professionals working in four Regional Offices, in the year of 2007, to outline the current profile of the Technical-Pedagogic Assistant in São Paulo State and his work conditions. The data gathered lead to the following findings: there are gaps in the identity process of the Technical-Pedagogic-Assistant, who see themselves as executors of the training programs, limited to follow and implement projects of educational policies in a central level; there is not an autonomous process of professional performance concerned to teacher s in service training at local level that allow them to carry on the real needs of the teachers; these professionals see themselves more as facilitators/mediators in the formation process than teachers formers; the real continuous formation looks like more as an occasional help than a planned enterprise to this end; there are ambiguities and conflicts stated by the Technical- Pedagogic Assistants related to their performance as agent of central offices or as spokesmen of the teachers who they interact professionally; they are professionals who are in a stabilization stage of their professional careers, in which the rotation, the overload of work and the relationship with the central offices that is inherent to their job, raise as difficulties in the process of reflection crucial to their occupation. Despite these circumstances and features, unlike it was supposed at the beginning of the survey, the role of the Technical-Pedagogic Assistant is more related to pedagogical procedures than bureaucratic tasks / Esta pesquisa focaliza o trabalho do Assistente Técnico-Pedagógico e as condições de sua realização nos locais de atuação deste profissional, ou seja, as Oficinas Pedagógicas das Diretorias de Ensino do Estado de São Paulo e possui como objetivos a) traçar um perfil do Assistente Técnico-Pedagógico e de suas condições de trabalho; b) identificar seu papel no sistema educacional paulista; c) resgatar a história, por meio dos registros e documentos oficiais das Oficinas Pedagógicas no Estado de São Paulo, seu locus de atuação profissional. O referencial teórico relaciona-se à formação continuada de professores, já que o sujeito da pesquisa, o Assistente Técnico-Pedagógico, na estrutura da rede pública estadual, é considerado agente de formação de professores. Assim, fornecem apoio teórico para a pesquisa: António Nóvoa, Gimeno Sacristán, Marcelo García e Henry Giroux (concepção de formação docente); Lawn & Ozga e Fernández Enguita (para análise do processo de proletarização da profissão docente) e, finalmente, Dubar (para a discussão do processo de construção da identidade profissional). Trata-se de pesquisa de natureza quantitativa e qualitativa, envolvendo estudo exploratório, analítico-descritivo das condições de trabalho do ATP na SEE-SP, que incluiu: a) análise de documentos para reconstituição da história das Oficinas Pedagógicas e levantamento de informações, por meio de formulário eletrônico preenchido integralmente por 966 ATP, entre os anos de 2006 e 2007 e b) questionário respondido por 20 destes profissionais em exercício em 04 Diretorias de Ensino, no ano de 2007, para delineamento do perfil atual dos ATP no Estado de São Paulo e de suas condições de trabalho. Os dados obtidos, organizados em quadros e tabelas, traçam o perfil do ATP e de sua atuação profissional na rede pública do Estado de São Paulo, bem como revelam o cotidiano desses profissionais, as possíveis contribuições do seu trabalho para a prática pedagógica dos professores em exercício e, por último, mas não menos importante, explicitam como tais profissionais se vêem na estrutura da SEESP. Os resultados permitem as seguintes constatações: há fissuras no processo identitário dos ATP, que se vêem mais como executores dos programas de formação, limitados a atender e executar as políticas educacionais propostas em nível central; não há um processo autônomo de atuação profissional no que se refere à política de formação continuada de professores em âmbito local, que lhes permita atuar como interlocutores das necessidades formativas dos professores; estes profissionais se percebem mais como facilitadores/mediadores do processo de formação, do que como formadores de professores; a formação continuada de fato exercida aproxima-se mais de um socorro eventual do que uma ação planejada para este fim; há ambigüidades e conflitos expressos pelos ATP entre atuar como um representante dos órgãos centralizados e ser um porta-voz dos docentes com os quais interagem profissionalmente; são profissionais que estão em fase de consolidação de suas carreiras profissionais, nas quais a rotatividade, o excesso de trabalho e a relação com os órgãos centrais próprios da função confirmam-se como aspectos dificultadores do processo de reflexão no exercício da função. Apesar de tais condições e características, diferentemente do que se presumia no início da pesquisa, a função dos ATP está mais voltada às ações pedagógicas do que às atividades burocráticas

Esta pesquisa nasce do encontro do olhar-expedicionário, sempre curioso e disposto a relacionar arte e ciência, com a Paragem das Conchas - nome atribuído à primeira sesmaria do Rio Grande do Sul, que corresponde hoje a um conjunto de municípios, dentre os quais, está Osório – lugar onde se desenvolvem as incursões aqui analisadas, entre os anos de 2012 e 2016. As experiências começam no ateliê, que funciona como um jardim onde se cultiva a linguagem do desenho, até que este lugar de produção de imagens abre-se e passa a ser compreendido como um observatório da natureza, fundindo-se, ao final, com a própria floresta. A principal pergunta que surge daí é: como se dá essa relação entre o ver e o conhecer a partir das experiências fenomenológicas com a paisagem que o meu trabalho artístico (obras em desenho, poesia, fotografia, objetos e instalação) proporciona? As rotas e o instrumental utilizados para as observações foram sendo redefinidos no próprio andar, como se fosse um Caminho de Peabiru, esse conjunto de trilhas indígenas cultivadas pelos Incas, que ligavam o Oceano Pacífico ao Atlântico. No andamento, foi preciso desaprender a ver o que eu pensava saber e aprender a ver o que não sabia que existia. O conjunto de trabalhos aqui apresentados forma um atlas onde procuro transmutar essas vivências por meio da linguagem poética. A narrativa divide a expedição em três momentos: Estudos sobre a terra | Estudos sobre a água | Estudos sobre o vento. A ação de expedir é interpretada em seu sentido literal de “liberar os pés das cadeias”. A pesquisa está dividida em dois volumes. No TOMO I apresento um percurso teórico em que o sol metaforiza, inicialmente, a relação entre o ver e o conhecer e, passo a passo, vai sendo eclipsado pela imagem da fogueira, que provoca uma queima de arquivo em que é necessário transmutar as memórias. O TOMO II é um livro de artista concebido a partir das travessias por TERRA (“Inventário de Fauna e Flora” e “Herbarium”), ÁGUA (“Travessia de Beija-Flor por águas doces”) e AR (“Tipologia do Mar – Escala Beaufort” e “Tipologia das nuvens – L. Howard”). / This research was created from the meeting of the expeditionary perspective, always curious and open to connect art and science, and Paragem das Conchas - the name given to the first sesmaria in Rio Grande do Sul - which today corresponds to a few different cities, amongst them Osório - the chosen spot for this expedition, which took place between 2012 and 2016. The experiences begin in the studio, which acts as a garden to cultivate the drawing language, till this image-production site opens up to be acknowledged as a nature observatory, ultimately merging with the forest itself. The main question that arises from that is: how does the relationship between seeing and knowing from phenomenological experiences in the landscape that my artistic work (drawing, poetry, photography, objects and art installation) provides me presents itself? The routes and instruments used in the observational trips were redefined while they were happening, such as in Caminho de Peabiru, the indigenous trails created by the Incas connecting the Pacific Ocean to the Atlantic. As the project went on, I had to unlearn how to see what I thought I knew and learn how to see what I did not know existed. The body of work presented here forms an atlas where I seek to transmute those experiences into a poetic narrative. The expedition was divided between three installments: Studies of the earth | Studies of the water | Studies of the wind. “Expedition” is interpreted here in a literal sense, that of “freeing the feet from the chains.” The research is divided in two volumes. In TOME I the theoretical path is presented, initially, in a way in which the sun acts as a metaphor of the relationship between seeing and knowing and, gradually, is eclipsed by the image of the bonfire, which leads to an indispensable documentation burning in order to transmute memories. TOME II is an artistic book created from crossings through land (“Inventário de Fauna e Flora” and “Herbarium”), water (“Travessia de Beija-Flor por águas doces”) and air (“Tipologia do Mar – Escala Beaufort” and “Tipologia das nuvens – L. Howard”).

Bagpipes and pipers, as cultural identifiers, are embedded within their national culture, charged with symbolisms. British authors have often viewed bagpipes as cultural icons, endowing them with connotations from devilish to virtuous, from rural to military. By analysing literary and artistic references one can perceive how the attitude towards the bagpipe changes with the evolution of Britain’s internal dynamics. Jacobitism contributed in casting a particular light on the bagpipe: it was the ‘voice of the rebellion’. In Scotland this constituted a reason for national pride, while in England the ‘common denominator’ of the Scot-enemy charged the bagpipe with the worst connotations. After Jacobitism stopped being seen as a threat, authors and artists came to view the bagpipe in a different light: the once negative icon was now imbued with ancestral values. The Scot – and the bagpipe by synecdoche – was romanticised: as James Boswell wrote, “The very Highland names, or the sound of a bagpipe, will stir my blood, and fill me with [...] a crowd of sensations with which sober rationality has nothing to do” (1785). The words of many Romantic authors contributed in characterising the instrument, endowing it with implications the influence of which is still relevant today.

Gegenstand der Arbeit war die Untersuchung der Rolle der Schwebegarnele Mysis relicta im pelagischen Nahrungsnetz des Breiten Luzins unter besonderer Berücksichtigung der trophischen Interaktionen zur Kleinen Maräne Coregonus albula. Schwerpunkte waren die Abundanz und räumlich-zeitliche Verteilung von M. relicta, C. albula und dem Zooplankton sowie die trophischen Beziehungen im Pelagial. Im Vergleich zu früheren Studien war M. relicta weiträumiger und mit höherer Dichte im Untersuchungsgebiet verbreitet. Dies war auf die Verbesserung der Wasserqualität zurückzuführen. Ähnliche Verteilungsmuster führten zu starken räumlichen Überlappungen von M. relicta und C. albula. M. relicta konsumierte vorwiegend abundantes Plankton. Es zeigte sich aber auch eine Präferenz für Cladocera. Aus den in vitro ermittelten Ingestionsraten wurde für die Situation im Freiland ein starker Fraßdruck von M. relicta auf das Zooplankton abgeleitet. In Kombination mit einer Überschneidung der Beutespektren führte das zur Nahrungskonkurrenz zwischen M. relicta und C. albula. Andererseits war M. relicta eine wichtige Beute für C. albula und wurde stark positiv selektiert. Die Fettsäuremuster der untersuchten Organismen waren überwiegend durch ihre Nahrung beeinflusst. Die Aufnahme von M. relicta wurde nicht durch das Auftreten spezifischer Fettsäuren bei C. albula nachgewiesen. Grundsätzlich entsprach der Energietransfer im Nahrungsnetz des Breiten Luzins allgemeinen Modellen mit 10 % Transfereffizienz zwischen benachbarten trophischen Ebenen. Im Einzelnen zeigten sich aber auch Abweichungen, die größtenteils auf M. relicta zurückzuführen waren. Durch ihre omnivore Ernährung und als Beute für C. albula schafft M. relicta zusätzliche Verbindungen zwischen den trophischen Ebenen. Insgesamt hat M. relicta einen weitreichenden Einfluss auf die Struktur und den Energietransfer des Nahrungsnetzes im Breiten Luzin, wodurch ihr Vorkommen für das Gewässer von besonderer Bedeutung ist. / The aim of the study was to investigate the role of the opossum shrimp Mysis relicta in the pelagic food web of Lake Breiter Luzin (Germany) with special focus on trophic interactions with European cisco Coregonus albula. Main aspects were the abundance and temporal and spatial distribution of M. relicta, C. albula and zooplankton as well as trophic relationships in the food web. As a result of improved water quality M. relicta showed a wider distribution and enhanced abundances in the study area than earlier investigations suggested. Due to similar diurnal vertical distributions a great spatial overlap was evident for M. relicta and C. albula. M. relicta fed mainly on highly abundant plankton. Besides, an overall preference for cladocerans was detected. By applying estimated in vitro feeding rates to field situations it could be shown that zooplankton was strongly exploited by M. relicta. This high demand combined with similar prey preferences of C. albula led to a strong food competition between M. relicta and C. albula. On the other hand M. relicta formed high amounts in the diet of C. albula and was always positively selected. Fatty acid composition of examined organisms resembled the composition found in their dietary resources. The intake of M. relicta could not be detected by a specific fatty acid composition in C. albula. Considering highest and lowest trophic levels, transfer efficiency in Lake Breiter Luzin fit into general models assuming a transfer of 10 % between neighbouring trophic levels. Transfer between intermediate trophic levels partly differed from this general pattern. This was connected to the existence of M. relicta. Being omnivorous and by providing an important food source for C. albula the mysid established additional links between trophic levels in the food web. In summary, M. relicta is a significant factor in structuring the food web of Lake Breiter Luzin and has profound impact on the entire lake ecosystem.