Regulatorische T-Zellen (Treg) eröffnen neue immuntherapeutische Wege zur Kontrolle unerwünschter Immunreaktionen, jedoch wirft die Heterogenität dieser Zellen die Frage auf, welche Treg-Population für die klinische Anwendung. Darauf basierend werden in dieser Arbeit drei Fragestellungen bearbeitet: i) Bestimmung der Häufigkeit von Tregs und deren Subpopulationen in verschiedenen Altersgruppen bei Empfängern einer Organtransplantation (Tx) und einer gesunden Kontrollgruppe; ii) Vergleich der Suppressorkapazität verschiedener Treg-Populationen und in vitro-Expansion der Zellen unter Erhaltung ihrer Funktionalität; iii) Klärung der Differenzierungsmerkmale von Tregs und deren Verknüpfung mit konventionellen T-Zellen (Tconv) mittels Analyse des T-Zell-Rezeptor- (TCR) Repertoires. Sowohl bei gesunden Probanden als auch bei Tx-Empfänger konnte eine altersabhängige Verschiebung von naiven (TregN) hin zu dominant zentralen Gedächtnis-Zellen (TregCM) beobachtet werden, Treg von Tx-Empfängern hatten mehr Effektor-Memory-Zellen (EM) und sie waren mehr aktiviert. In Bezug auf die Kontrolle der frühen Tconv zeigen TregCM eine erhöhte Suppressorkapazität im Vergleich zu TregN. Außerdem sind im Gegensatz zu TregN nur TregCM dazu in der Lage, Apoptose bei Responderzellen zu induzieren. Der Grund hierfür könnte in der stärkeren Expression von CTLA-4 auf TregM liegen. Die Expansionskultur führte zur phänotypischen Veränderung der TregN, deren Umwandlung in TregCM mit einer verbesserten Suppressoraktivität verbunden ist. Die Daten legen nahe, dass das Expandieren mit gesamt Treg für die Adoptive-Treg-Therapie optimal sind, da sie der größte Anteil von ihnen die hochpotenten TregCM sind. TCR-Studien mittels Next Generation Sequencing zeigen weiter, dass TregM aus TregN entstehen, anstatt aus Tconv, in einem Antigen-gesteuerten Prozess. Diese Daten belegen erstmalig neue Erkenntnisse hinsichtlich der Unterschiede der TCR-Repertoires von TregM und Tconv beim Menschen. / Regulatory T cells (Treg) offer new immunotherapeutic options to control undesired immune reactions, but the heterogeinetiy of Treg raises the question which Treg population should be used for clinical translation Thus, this project involves three main parts: i) investigating Treg frequency and subsets distribution with age in healthy donors and transplant (Tx) patients; ii) comparing the suppressive capacity of Treg subsets and expanding them in vitro without losing functionality; iii) clarifyjing the differiation relationship of Treg subsets and their relation to conventional T cells (Tconv) by T cell receptor (TCR) repertoire analysis. From both healthy donors and Tx patients, an age-dependent shift from naïve Treg (TregN) to the dominant central-memory Treg (TregCM) was observed,; However,Treg in Tx patients contained more effector-memory EM cells, , and they were pre-activated due to the exposure to allo antigens,. Regarding control of early Tconv activation, TregCM showed enhanced suppressive capacity compared to TregN; furthermore, only TregCM could induce apoptosis of responder cells while TregN could not, which may result from thehigherexpression of cytotoxic T-lymphocyte antigen 4 (CTLA-4) on TregM. Following in vitro expansion of the Treg subsets, however, TregN converted mainly into TregCM phenotype with enhanced suppression activity. The poor proliferation capacity of TregEM might indicate EM as the terminal differential stage. These data suggest that expansion with total Treg is optimal for adoptive Treg therapy as the majority of them are the highly potent TregCM. Lastly, TCR repertoire study by next generation sequencing (NGS) indicate that TregM derived from TregN rather than Tconv in an antigen-driven process. The highest similarity of the TCR repertoires was observed between TregCM and TregEM. These data reveal new insights for the first time into the distinct TCR repertoires of Treg subsets and Tconv in human by NGS technology.

Les anticorps catalytiques (ou abzyme) ont fait l’objet de nombreuses recherches et ont été produits pour réaliser de nombreuses réactions. Ces protéines ont été ensuite découvertes dans le sérum d’individus sains ou atteints de pathologies, dont les pathologies autoimmunes. Les études suggèrent que ces abzymes peuvent avoir des effets bénéfiques ou délétères sur la santé des individus. L’origine des anticorps catalytiques et leur rôle restent ambigus et doivent être approfondis. Nous avons développé une nouvelle stratégie visant à étudier les abzymes, basée sur la technologie du phage display. Nous avons construit 4 banques de fragments d’anticorps, chacune présentant un répertoire immun différent (fond génétique et état d’immunitaire) : saine et naïve, saine et immunisée, autoimmune et naïve, et autoimmune et immunisée. Les stratégies d’amplification et de clonage des régions variables des immunoglobulines ont été conçues afin d’optimiser la taille et la diversité des banques. Nous avons rassemblé les 4 banques en une banque unique élargie contenant 2.7×109 séquences. L’analyse des séquences a mis en évidence des différences dans les profils d’expression des sous-groupes de gènes selon la banque. Nous avons ensuite procédé à la sélection d’abzymes à activité β-lactamase en utilisant deux cibles : un peptide cyclique, et un dérivé de sulfone pénam, inhibiteurs de l’enzyme. Nous avons sélectionné 5 abzymes. Chacun de ces immunoglobulines ont des séquences protéiques propres, incluant un potentiel site actif. Ces résultats montrent que différents motifs peuvent assurer la fonction catalytique de la β-lactamase, confirmant la flexibilité moléculaire de cette enzyme. / Catalytic antibodies (or abzymes) have been the focus numerous studies for some decades and have been produced with the ability to catalyze a wide range of reactions. They have also been discovered naturally in normal physiological and pathological conditions, notably on the background of autoimmune disease. Some have beneficial effects and others are detrimental to individual’s health. Hence, the origin of abzymes and their role in the immune response are ambiguous and must be enhanced. We have developed a novel strategy for the study of abzymes based on the phage display technology. We have constructed 4 libraries representing 4 murine immune repertoires with different genetic backgrounds and immunological states : healthy and naïve, healthy and immunized, autoimmune and naïve , and autoimmune and immunized. The strategies for the amplification and cloning of the immunoglobulin (lg) variable regions have been designed to optimize the size and diversity of the libraries. We have been able to pool the four libraries to create a large repertoire of size 2.7x109. After sequence analysis, we have found a number of statistically significant differences between the libraries. We have then used two strategically chosen targets to select for antibodies endowed with β lactamase activity : a cycle peptide and a penam sulfone, both inhibitors of the enzyme. We have selected for a total of 5 lgs endowed with β lactamase activity. The selected abzymes have different amino acid sequences. 3D modeling has provides insights on potential active sites demonstrating the ability of different structures to maintain the β lactamase activity and confirming the flexibility of the active site.

Submitted by Maria Aparecida (cidazen@gmail.com) on 2017-04-12T13:19:27Z No. of bitstreams: 1 Jadeylson ferreira.pdf: 7872774 bytes, checksum: d317110bb9cada61e97d1ce7a7475d42 (MD5) / Made available in DSpace on 2017-04-12T13:19:27Z (GMT). No. of bitstreams: 1 Jadeylson ferreira.pdf: 7872774 bytes, checksum: d317110bb9cada61e97d1ce7a7475d42 (MD5) Previous issue date: 2015-08-26 / This dissertation is embedded in socio-environmental conflicts and object the experience of political mobilization of the cashew tree located in the village Rural II of São Luís do Maranhão, in the neighborhood of the complex Port of Saint Louis. Analyzes the resistance movement of the village threatened by the installation of the port Terminal of Saint Louis, the WRP Management company of ports and terminals LTDA. in this context, the study attempts to reconstruct the process of resistance that generated a series of class-action suits from alliances made with neighbouring settlements, institutions linked to the Federal University of Maranhão, Church Catholic actors local politicians, social movements and entities. The analysis turns to the issue of arena, mediated by power relations about space in dispute, having as focus, the proposed installation of the extractive reserve of Tauá-Mirim. Still, the analysis considers the repertories of collective action, accumulated by the actors throughout the process of social resistance in areas threatened by the process of expansion of logistics infrastructure describing the forms of action employed between the months of July 2014 and February 2015. 15 meetings were analysed, 03 public hearings, 04 08 interviews and demonstrations. In addition to magazines, reports, production reports, newspapers, TV programs, and master plan documents on the legal question of the cashew tree. We tried to give visibility to forms of mobilisation of actors and their performances that revealed the importance of movement formed around the community. / Esta tesis doctoral está incrustada en los conflictos socio-ambientales y objeto de la experiencia de movilización política del árbol de nuez de la India situado en el pueblo II rural de São Luís do Maranhão, en el barrio del complejo Puerto de Saint Louis. Analiza el movimiento de resistencia del pueblo amenazado por la instalación del puerto Terminal de San Luis, la empresa WRP de puertos y terminales LTDA en este contexto, el estudio intenta reconstruir el proceso de resistencia que genera una serie de acción de clase se adapte de alianzas con asentamientos vecinos, instituciones vinculadas a la Universidad Federal de Maranhão, iglesia Actores Católicos locales políticos, movimientos sociales y entidades. El análisis se convierte en el tema de la arena, mediado por relaciones de poder sobre el espacio en disputa, después de haber como enfoque, la instalación de la reserva extractivista de Tauá-Mirim. Aún así, el análisis considera los repertorios de acción colectiva, acumulada por los actores durante el proceso de resistencia social en las zonas amenazadas por el proceso de expansión de la infraestructura logística que describe las formas de acción empleada entre los meses de julio de 2014 y de 2015 de febrero. se analizaron 15 reuniones, 03 audiencias públicas, 04 08 entrevistas y demostraciones. Además de revistas, informes, reportes de producción, periódicos, programas de TV y documentos del plan maestro sobre la cuestión jurídica del árbol de la nuez de la India. Hemos tratado de dar visibilidad a las formas de movilización de actores y sus performances que revelaron la importancia del movimiento formado alrededor de la comunidad. / Esta dissertação está inserida na temática dos conflitos socioambientais e tem como objeto a experiência de mobilização política do povoado Cajueiro localizado na Zona Rural II do município de São Luís do Maranhão, nas circunvizinhanças do Complexo Portuário de São Luís. Analisa o movimento de resistência do referido povoado ameaçado pela instalação do Terminal Portuário de São Luís, da empresa WPR Gestão de Portos e Terminais LTDA. Nesse contexto, o estudo tenta reconstruir o processo de resistência que gerou uma série de ações coletivas a partir de alianças realizadas com povoados vizinhos, instituições ligadas à Universidade Federal do Maranhão, Igreja Católica, atores políticos locais, movimentos sociais e entidades. A análise se volta para a questão da arena, mediado por relações de poder sobre o espaço em disputa, tendo como enfoque, a proposta de instalação da Reserva Extrativista de Tauá-Mirim. Considera, ainda, na análise os repertórios de ação coletivas, acumulados pelos atores sociais ao longo do processo de resistência nos territórios ameaçados pelo processo de expansão da infraestrutura de logística descrevendo as formas de ação empregadas entre os meses de julho de 2014 e fevereiro de 2015. Foram analisadas 15 reuniões, 03 audiências públicas, 04 manifestações e realizada 08 entrevistas. Além de revistas, informes, relatórios de produção, jornais, programas de TV, plano mestre e documentos jurídicos sobre a questão do Cajueiro. Procurou-se dar visibilidade às formas de mobilização dos atores e suas atuações que revelaram a importância do movimento que se formou em torno da comunidade.

Esta pesquisa tem como principal objeto de estudo os repertórios de ação e mobilização utilizados durante e ao redor da Ocupação da Câmara de Vereadores de Porto Alegre (10-18 de julho de 2013). A partir da experiência etnográfica e do engajamento militante no Bloco de Lutas pelo Transporte Público, busca-se compreender de que formas o Bloco se organizou e quais são os valores que nortearam esta organização. Ao mesmo tempo, atenta-se para os sujeitos responsáveis por essas práticas e por esses meios, procurando identificar as redes sociais que os aproximam e suas trajetórias de vida. Assembleias, atos, comissões, ocupações, redes sociais e cine-debates servem para analisar as disputas dentro do Bloco de Lutas e ao redor da Ocupação da Câmara de Vereadores de Porto Alegre. É priorizado o recorte etnográfico e o diálogo com outros autores que pensam as práticas de governo e os sentidos das políticas nesses tempos e nesses espaços. Finalmente, identificam-se as divergências estratégicas como o principal problema do Bloco, as ocupações como uma forma de ação coletiva integral e a potencialidade da antropologia pública e das camadas de autoria. / This research has as its main object of study the repertoires of action and mobilization used in and around the Occupation of the City Council of Porto Alegre (10-18 July 2013). From the ethnographic experience and militant engagement in the Fight Block for Public Transportation, we seek to understand what this Block was organized like, and what values are the ones that guided this organization. Meanwhile, we focused on the subjects responsible for these practices and means, trying to identify social networks that link them and their life trajectories. Meetings, acts, commissions, occupations, social networks and cine-debates served to analyze disputes within the Fight Block and about the Occupation of the City Council of Porto Alegre. It is prioritized the ethnographic research and dialogue with other authors who think government practices and senses of policies in these times and spaces. Finally, it identifies the strategic divergences as the main problem of the Block, the occupations as a form of full collective action and the potential of public anthropology and authory layers.

Esta pesquisa tem como principal objeto de estudo os repertórios de ação e mobilização utilizados durante e ao redor da Ocupação da Câmara de Vereadores de Porto Alegre (10-18 de julho de 2013). A partir da experiência etnográfica e do engajamento militante no Bloco de Lutas pelo Transporte Público, busca-se compreender de que formas o Bloco se organizou e quais são os valores que nortearam esta organização. Ao mesmo tempo, atenta-se para os sujeitos responsáveis por essas práticas e por esses meios, procurando identificar as redes sociais que os aproximam e suas trajetórias de vida. Assembleias, atos, comissões, ocupações, redes sociais e cine-debates servem para analisar as disputas dentro do Bloco de Lutas e ao redor da Ocupação da Câmara de Vereadores de Porto Alegre. É priorizado o recorte etnográfico e o diálogo com outros autores que pensam as práticas de governo e os sentidos das políticas nesses tempos e nesses espaços. Finalmente, identificam-se as divergências estratégicas como o principal problema do Bloco, as ocupações como uma forma de ação coletiva integral e a potencialidade da antropologia pública e das camadas de autoria. / This research has as its main object of study the repertoires of action and mobilization used in and around the Occupation of the City Council of Porto Alegre (10-18 July 2013). From the ethnographic experience and militant engagement in the Fight Block for Public Transportation, we seek to understand what this Block was organized like, and what values are the ones that guided this organization. Meanwhile, we focused on the subjects responsible for these practices and means, trying to identify social networks that link them and their life trajectories. Meetings, acts, commissions, occupations, social networks and cine-debates served to analyze disputes within the Fight Block and about the Occupation of the City Council of Porto Alegre. It is prioritized the ethnographic research and dialogue with other authors who think government practices and senses of policies in these times and spaces. Finally, it identifies the strategic divergences as the main problem of the Block, the occupations as a form of full collective action and the potential of public anthropology and authory layers.

Esta pesquisa tem como principal objeto de estudo os repertórios de ação e mobilização utilizados durante e ao redor da Ocupação da Câmara de Vereadores de Porto Alegre (10-18 de julho de 2013). A partir da experiência etnográfica e do engajamento militante no Bloco de Lutas pelo Transporte Público, busca-se compreender de que formas o Bloco se organizou e quais são os valores que nortearam esta organização. Ao mesmo tempo, atenta-se para os sujeitos responsáveis por essas práticas e por esses meios, procurando identificar as redes sociais que os aproximam e suas trajetórias de vida. Assembleias, atos, comissões, ocupações, redes sociais e cine-debates servem para analisar as disputas dentro do Bloco de Lutas e ao redor da Ocupação da Câmara de Vereadores de Porto Alegre. É priorizado o recorte etnográfico e o diálogo com outros autores que pensam as práticas de governo e os sentidos das políticas nesses tempos e nesses espaços. Finalmente, identificam-se as divergências estratégicas como o principal problema do Bloco, as ocupações como uma forma de ação coletiva integral e a potencialidade da antropologia pública e das camadas de autoria. / This research has as its main object of study the repertoires of action and mobilization used in and around the Occupation of the City Council of Porto Alegre (10-18 July 2013). From the ethnographic experience and militant engagement in the Fight Block for Public Transportation, we seek to understand what this Block was organized like, and what values are the ones that guided this organization. Meanwhile, we focused on the subjects responsible for these practices and means, trying to identify social networks that link them and their life trajectories. Meetings, acts, commissions, occupations, social networks and cine-debates served to analyze disputes within the Fight Block and about the Occupation of the City Council of Porto Alegre. It is prioritized the ethnographic research and dialogue with other authors who think government practices and senses of policies in these times and spaces. Finally, it identifies the strategic divergences as the main problem of the Block, the occupations as a form of full collective action and the potential of public anthropology and authory layers.

1900-talets början var en tid med olika arbetsmarknadskonflikter. Det förekom strejker, demonstrationer, kravaller och agitationsmöten. Dessa konflikter utspelade sig i ett samhälle där arbetarrörelsen började organisera sig alltmer i fackföreningar och i arbetarkommuner för att få politiskt inflytande och inflytande över sin arbetssituation. Det gjorde att arbetarrörelsen hamnade i sociala konfrontationer med omgivning, myndigheter och arbetsgivare. Syftet med uppsatsen är att undersöka kopplingen mellan klassformering i ett identitetsperspektiv och framväxten av konfliktrepertoarer i det tidiga 1900-talets fackliga organisationssträvanden. Frågeställningarna utgår från att identifiera konfliktrepertoarer i sociala konfrontationer och vilka av dessa som används för att skapa klassamhörighet i olika sociala, fackliga och politiska sammanhang. För att studera sociala konfrontationer, konfliktrepertoarer och identitetsskapande inom arbetarrörelsen har källmaterial efter fackföreningar vid Bergslagernas järnvägar i Åmål använts. Uppsatsen är ett bidrag till arbetarhistoria och källmaterialet undersöks utifrån teorin i forskningsfältet Contentious Politics Studies. Uppsatsen har även en ikonografisk ansats eftersom källmaterialet innehåller visuella uttryck. I undersökningen har fyra olika sociala konfrontationer identifierats. Dessa är: Agitation och politisk mobilisering 1908 - 1911, Oskar Lundströms avskedande 1909, Lokmannastrejken 1919 och Den stora järnvägsstrejken 1922. Ett antal konfliktrepertoarer identifieras och uppsatsens resultat är att konfliktrepertoarerna utvecklas och förfinas över tid. Kraven blir mer tydligt formulerade och handlingar tillsammans med visuell kultur stärker den politiska identiteten. Konfliktrepertoarer, handlingar och identiteter blir därigenom meningsskapande i klassformeringen. / The beginning of the 20th century was a time of various labor market conflicts. There were strikes, demonstrations, riots and agitation meetings. These conflicts took place in a society where the labor movement began to organize itself in trade unions in order to gain political influence and influence over their work situation. As a result, the labor movement ended up in confrontations with the environment, authorities and employers. The main purpose of the essay is to investigate the connection between class affiliation in an identity perspective and the emergence of contentious repertoires in the early 20th century trade union organizational efforts. The essay is based on theories of Contentious Politics Studies. The investigated material is archives of trade unions at Bergslagernas railways in Åmål. Four different contentious politics have been identified. These are: 1. Agitation and political mobilization 1908 - 1911, 2. Oskar Lundström's dismissal 1909, 2. The engine driver strike in 1919 and 4. The great railway strike in 1922. The result of the essay is that the contentious repertoires are developed and refined over time. The claim making are more clearly formulated and contentious performances together with visual culture strengthen the political identity. Contentious repertoires, contentious performances and political identities thereby create meaning in class affiliation.

The diploma thesis Public sphere in networked society concerns about the relation of public sphere and cyberspace. Cyberspace is defined as new social institution, which is not embodied Habermasian normative ideal of critical public sphere, but in contrary it constitute new forms of inequalities and new forms of fragmentarization and commercialization. Explored are therefore also theories which critically deal with concept of public sphere and better describe the reality of cyberspace. The expansion of Cyberspace and horizontal communication network also relate with transformation of contentious politics. The thesis provides an overview of historical development of new action repertoire of contention - virtual sit-in. As an embodiment of all these societal shifts, which are seen as an elements of change in power balance, is presented Operation Payback orchestrated by hacktivist group Anonymous. Keywords Cyberspace, public sphere, hacktivism, action repertoires, repertoires of contention, virtual sit-in, electronic civil disobedience, Anonymous, Operation Payback

På grund av mångfalden i dagens svenska skolor kan inte alltid traditionellt arbetssätt i matematikundervisning främja elever att utveckla sina förmågor såsom analys- och resonemangsförmåga. Läroboksstyrda lektioner ger inte elever möjligheter att komma till tals, lyssna på andras resonemang, tänka kritiskt och analysera andras tankesätt. Därför som matematiklärare blir det intressant att undersöka hur lärarna på alla stadier (låg-, mellan- respektive högstadiet) använder sig av dialogisk undervisning och vilken form av dialogisk undervisning som dominerar i respektive stadie. Därför genomfördes en fallstudie av dialogisk undervisning inom ramen för detta självständiga arbete. Datainsamlinggenomfördes genom observation samt ljudinspelning, i en lågstadie-, i en mellanstadie- och i en högstadieklass, sammanlagt nio lektioner. För att kunna analysera data har Robin Alexanders välkända ramverk för dialogisk undervisning använts (presenterat bl.a. i artikeln Developing dialogic teaching, 2018). I ramverket kategoriseras undervisningen utifrån repertoarer och principer som belyser olika aspekter av dialoger i klassrummet. Fallstudien visade att lektioner präglade av dialog förekom mest på låg- och mellanstadiet och i mindre utsträckning på högstadiet. Lärarnas främsta teaching talk bestod av recitation (initiera-respons-feedback) men kompletterat med hur och varför i hög grad i låg- och mellanstadielektioner med syfte att föra samtalet vidare vilket i sin tur möjliggjorde för att eleverna att komma till tals för att förklara och motivera sitt tänkande till skillnad från på högstadielektionerna där elevernas främsta learning talk bestod av korta svar. / Due to the diversity in today's Swedish schools, traditional methods in mathematics teaching can’t always promote students to develop their abilities such as analytical and reasoning skills. Textbook-guided lessons don’t give students opportunities to speak, listen to others thoughts, think critically and analyze the thinking of others. Therefore, as a mathematics teacher, it will be interesting to investigate how teachers at all stages (primary, intermediate, and upper-secondary) use dialogic teaching and which form of dialogic teaching dominates in each stage. Therefore, a case study of dialogic teaching was conducted within the framework of this independent work. Data collection was carried out through observation and sound recording, in an elementary school, in an intermediate school and in a high school class, a total of nine lessons. In order to be able to analyze data, Robin Alexander's well-known framework for dialogic teaching has been used (presented in the article Developing dialogic teaching, 2018). The framework categorizes teaching on the basis of repertoires and principles that illuminate various aspects of dialogues in the classroom. The case study showed that lessons characterized by dialogue occurred mostly in primary and middle school and to a lesser extent in high school. The teachers' main teaching talk consisted of recitation (initiate-response-feedback) but supplemented with how and why to a large extent in the primary and intermediate stage with the aim of passing on the conversation, which in turn made it possible for the students to speak to explain and motivate their thinking unlike in high school where the students' main learning talk consisted of short answers.

This study set out to investigate how students construct their identities. Throughout their socialisation into academia, students are confronted with the paradox of learning as they negotiate the opposing discourses of enslavement and mastery that construct higher education. Utilising a critical discursive psychology approach this research aimed to examine the implications this paradox holds for the development of students’ identities. In-depth interviews with five master’s degree students allowed for an examination of the linguistic resources available for students to draw on in constructing their accounts of student-hood. Analysis of the interpretive repertoires and ideological dilemmas in the text revealed the uptake of contradictory subject positions in participants’ navigation of academic discourse. In order to address the inconsistencies associated with these conflicting ways of being a student, participants ‘worked’ a face in their interactions with academic discourse. Their face-work served to address the paradox by integrating the contradictory positions evident in their accounts. It is in the agency displayed in the integration of these disparate positions that the emancipating student is revealed. / Psychology / M.A. (Research Consultation)