Spinal cord injuries result in permanent loss of motor function, leaving those affected with long term physical and financial burdens. Strategies for spinal cord injury repair must overcome unique challenges due to scar tissue that seals off the injury site, preventing regeneration. Tissue engineering can address these challenges with scaffolds that serve as cell- and drug-delivery tools, replacing damaged tissue while simultaneously addressing the inhibitory environment on a biochemical level. To advance this approach, the choice of cells, biomaterial matrix, and drug delivery system must be investigated and evaluated. This research seeks to evaluate (1) the behaviour of murine induced pluripotent stem cells in previously characterized 3D fibrin matrices; (2) the 3D fibrin matrix as a platform to support the differentiation of human induced pluripotent stem cells; and (3) the ability of an affinity-based drug delivery system to control the release of emerging spinal cord injury therapeutic, heat shock protein 70 from fibrin scaffolds. / Graduate / 0541 / amy.lynn.montgomery@gmail.com

In this Master’s Thesis Research the results can be summarized from two major tasks: (1) In our first task, we utilized our two protein system (BAG-1 and HSP 70) as part of beta testing of a computational software 1 that can take three dimensional x-ray crystallography information about protein complexes and predict the strength of atom –atom interactions between amino-acid residues Open Contact predicts binding hotspots that can be used to identify short amino acid chains or peptides that mimic that particular binding segment of the larger protein. These peptides are called pepidyl-biomimetics. The peptide can potentially act as an antagonist drug by binding to the hotspot on protein A before protein B of the A-B complex can form. Two potential peptide candidates were identified. In particular, a helical peptide was discovered that demonstrated a variety of different types of atom-atom interactions. (2) Our second task is to experimentally test the helical peptide for its ability to block the binding that occurs between the 70-kilodalton Heat Shock Protein (HSP-70) and the Bcl-2 Associated Athanogene (BAG-1) Protein. As reviewed here, the binding between HSP-70 and BAG-1 elicits a cascade of cellular events that maintain high cancer growth rates and a greatly increased resistance to chemotherapy. In addition, BAG-1 has been implicated in a number of onco-signal pathways, as reviewed here, and its inhibition alone is believed to act as an agent against cancer cell growth

[pt] Entre 1971 e 1978 o artista plástico carioca Hélio Oiticica (1937-1980) morou em Manhattan, Nova York. Batizada por Oiticica de Babylon, é durante sua estadia na cidade que ele investe grande parte de seu trabalho em um novo projeto: publicar uma série de textos escritos nesse período, em um livro cujo formato e conteúdo permaneceram em constante transformação ao longo dos anos, sem atingir um resultado final. Batizado com alguns nomes como Newyorkaises e Conglomerado, o projeto de publicação torna- se o epicentro da produção de Oiticica e, ao mesmo tempo, uma promessa não realizada. A Tese visa analisar a relação produtiva entre a obra de Oiticica e a escritura, além da forte presença da literatura em seus trabalhos e reflexões. A análise dessa relação percorrerá alguns espaços criativos desse escritor- leitor, como seu arquivo, seus escritos pessoais, cartas, cadernos e fontes de leitura por ele utilizadas. Ao apresentar e analisar documentos de pouca ou nenhuma divulgação escritos por Hélio Oiticica, a Tese pretende não só ampliar os debates sobre arte e literatura em geral como divulgar novas temáticas e possibilidades de pesquisa em relação à sua obra. / [en] From 1971 to 1978, Hélio Oiticica (1937-1980), a native of Rio de Janeiro, lived in Manhattan. During his sojourn in New York, a city he referred to as Babylon, he put much of his effort into a new project: that of publishing a number of texts written in this period as a book whose format and content would constantly change throughout the years, never reaching a final result. Variously known as Newyorkaises and Conglomerado, the publication project became both the epicenter of Oiticica`s production and a promise that never came to fruition. This dissertation analyzes the relationship between Oiticica`s art and his writings and addresses the marked presence of literature in both his works and his reflections. The analysis of the relation between the two takes into account different manifestations of this writer/reader`s creativity, such as his archive, intimate writings, letters and notebooks, as well as his reading. By presenting and analyzing little-known or previously unpublished texts by Oiticica, this dissertation aims not only to broaden the scope of debates on art and literature in general but also to disseminate new themes and possibilities of research into Oiticica`s work.

Este estudo busca examinar o teatro de Chico Buarque enquanto dramaturgia, tratar de sua concretização em espetáculo, expor a recepção crítica de cada texto e das montagens mais significativas, relacionar o conjunto da obra ao contexto histórico dos anos de 1968 a 1978 no Brasil. Acompanhando a trajetória do teatro de Chico Buarque, este trabalho traça um painel das difíceis relações entre os artistas, protagonistas de uma atividade que requer a liberdade como princípio e fim, e os homens da última ditadura militar da história brasileira, impositores da censura e praticantes da repressão oficial ou à margem da lei. A presente dissertação compõe-se por uma introdução ao tema, cinco ensaios relativos a cada uma das obras dramatúrgicas do autor e algumas considerações finais. / This study intends to examine the theater by Chico Buarque as playwriting, broach its realization as dramatic spectacle, expose the critic’s judgements on the author’s texts and their most important putting on a show, relate his plays with the historical context of the 1968 to 1978 decade in Brazil. Observing the trajectory of the theater by Chico Buarque, this work delineates a panel of the conflitive relationships between the artists − who are engaged in an activity that requires liberty as principle and purpose − and the men committed to inflict censure and execute the official or lawless repression during the last military dictatorship in Brazil. This dissertation is composed by an introduction to the theme, five essays concerning to each dramatic work by the author and some final considerations.

Este trabalho apresenta uma investigação sobre a fotografia produzida por artistas nos anos 1960 e 1970, a partir de uma análise discursiva dos textos que os próprios artistas escreveram na época. Proponho que a especificidade da concepção de fotografia dos anos 1960 e 1970 é resultado de um processo complexo: habitando uma exterioridade selvagem da disciplina das artes visuais naquele momento, a fotografia é escolhida por artistas como uma estratégia importante em uma disputa discursiva pelas definições de arte que resulta na sua formação como objeto para a disciplina das artes visuais. Esta investigação se desdobra em três capítulos: As Fontes de Pesquisa; A Fotografia-Qualquer; Fotografia e Práticas Artísticas – os Discursos dos Artistas nos Anos 1960 e 1970. No primeiro capítulo desenvolvo uma discussão sobre o texto de artista e sua relevância para a compreensão da arte produzida nas décadas de 1960 e 1970, pela análise comparativa de quatro livros que reúnem textos de artistas da época, com o intuito de explicitar o modo como estes escritos são incluídos no campo teórico das artes visuais, pela sua republicação, que se coloca como uma reapresentação (com um consequente deslocamento de seus contextos originais, edição e, muitas vezes, recortes), o que interfere em sua existência e significado para o conhecimento artístico. Nos capítulos 2 e 3, apresento o resultado de uma investigação que teve como objetivo extrair dos discursos dos artistas, datados dos anos 1960 e 1970, qual o papel que a fotografia desempenhava em suas práticas artísticas no contexto maior da arte daquele período. Persigo a ideia da fotografia como um dispositivo de despersonalização do artista como gênio criador, como figura especial que produz objetos especiais e, portanto, distingue-se das outras pessoas. Esta qualidade da fotografia-qualquer é enfatizada em textos de artistas dos referidos anos em uma celebração da possibilidade da anti-arte que resultava da utilização da fotografia como medium, na apropriação do que havia de menos especial em termos de técnica e material para a produção de imagens e se contrapunha à arte que eles chamavam de tradicional ou convencional. Ainda centralizo minha atenção, nos textos dos artistas, no modo como eles abordam seus trabalhos, a fim de destilar daí três papéis que a fotografia pode desempenhar em suas práticas artísticas: a fotografia como documento; a fotografia integrada à prática artística; a fotografia como trabalho de arte. Enquanto tendências extraídas dos modos de apropriação da fotografia como medium para a produção, esses agrupamentos têm a função de organizar, por semelhança e diferença, as abordagens discursivas dos artistas sobre suas práticas, a partir de como eles elaboraram seu fazer e determinaram o lócus de seu trabalho – em outras palavras, o que, para cada um deles, constitui o trabalho de arte propriamente dito em meio aos vários elementos que compõem sua prática artística. A fotografia na arte existe em virtude do discurso – tanto visual quanto textual – que a toma como objeto, e, neste sentido, estava sendo inventada para aquele momento, nos escritos e trabalhos dos artistas. A presença da fotografia na prática artística das décadas de 1960 e 1970, abordada a partir dos discursos dos artistas, revelou-se como um processo complexo de estabelecimento da fotografia como um objeto para o saber artístico, do qual se pode falar e para o qual se forma um vocabulário específico, possibilitando que ela se coloque como mais um medium para a produção artística, entre outros e em relação a eles. / This thesis presents an investigation into the photography produced by artists in the 1960s and 1970s, based on a discursive analysis of texts that the artists themselves wrote at the time. I propose that the specificity of the conception of photography from the 1960s and 1970s is the outcome of a complex process: inhabiting a wild exteriority of the visual arts discipline at that moment, photography is chosen by artists as an important strategy in a discursive dispute for definitions of art which results in its constitution as an object to the visual arts discipline. This investigation unfolds in three chapters: Sources of Research; The Photography-Whatever; Photography and Artistic Practices – Discourses of Artists in the Years 1960 and 1970. In the first chapter I carry out a discussion on the artist’s text and its relevance for understanding the art produced in the 1960s and 1970s, by means of a comparative analysis of four books that gather texts of artists of the time, in order to clarify how these writings are included in the theoretical field of visual arts, through their republication, which arises as a re-presentation (with a consequent displacement from their original contexts, editing, and often cuts), and so interferes with their existence and meaning for the artistic knowledge. In chapters 2 and 3, I present the result of a research that seeks to extract, from speeches of artists dating from the 1960s and 1970s, the role played by photography in their artistic practices in the larger context of art of that period. I pursue the idea of photography as a device of depersonalization of the artist as creative genius, as a special character who produces special objects and therefore distinguishes himself from other people. Such quality of the photography-whatever is stressed in texts of artists from those years in a celebration of the possibility of anti-art that resulted from the usage of photography as a medium, through an appropriation of the least special techniques and materials available at that time for the production of pictures and was opposed to the art that they called traditional or conventional. I also focus my attention, in the artists’ texts, in how they approach their own work, in order to withdraw three roles that photography can play in their artistic practices: the photograph as a document; the photograph integrated into the artistic practice; the photograph as an art work. While trends drawn from the ways of appropriation of photography as a medium for production, these groups have the task of organizing, by similarity and difference, the discursive approaches of the artists about their practices, based on how they developed their doing and determined the locus of their work – in other words, that which, for each of them, constitutes the work of art itself among the various elements that comprise his artistic practice. Photography in the arts exists by virtue of the discourse – both visual and textual – that takes it as an object, and in this sense it was being invented for that time, in the writings and works of the artists. The presence of photography in the artistic practice in the 1960s and 1970s, approached by means of a research into the discourses of artists, has shown itself as a complex establishment process of photography as an object to the artistic knowledge, an object of which one can speak and for which a specific vocabulary is formed, enabling it to place itself as a new medium among others (and in relation to them) for artistic production.

<p>Det finns idag en stark trend bland företag att outsourca hela eller delar av sin ekonomi-funktion, det vill säga att anlita en extern redovisningsbyrå.<strong> </strong>Sveriges Redovisningskonsulters Förbund, SRF, har idag 4 500 auktoriserade redovisningskonsulter som medlemmar. Dessa anlitas av mer än 200 000 företag. Denna ökande trend har givit upphov till en helt ny och unik problematik kring hur granskningen av dessa företag ska gå till. Det finns i dagsläget en revisionsstandard, <em>RS 402: Revisorns övervägande vid revision av företag som anlitar servicebyråer</em>, som föreskriver att revisorn ska ta hänsyn till hur redovisningsbyrån påverkar företagens redovisningssystem och interna kontroll.</p><p> </p><p>Uppsatsen är en kvalitativ flerfallsstudie vars syfte är att undersöka vilka ställningstaganden revisorn ställs inför vid revision av företag som outsourcar ekonomifunktionen. Enligt uppsatsens utredningsmodell är revisorns viktigaste ställningstagande huruvida utlagda funktioner är väsentliga för företagets interna kontroll över finansiell rapportering. Om de bedöms väsentliga ska revisionsbevis i form av en RS 402 inhämtas eller då detta saknas test av uppdragstagarens kontroller genomföras. Den empiriska undersökningen visar dock att de revisorer som arbetar med små företag bedömer redovisningskonsultens kunskaper vara det viktigaste ställningstagandet. Få av dessa revisorer har kommit i kontakt med RS 402 i det praktiska arbetet.</p><p> </p><p>En ny revisionsstandard på området, ISAE 3402, håller dock på att utarbetas av International Auditing and Assurance Standards Board (IAASB) och förväntas införas tidigast under hösten 2009. Uppsatsen utreder även hur revisionsprocessen kommer att påverkas av införandet av den nya standarden. Den största förändringen i jämförelse med RS 402 förväntas bli att ledningen av servicebyrån på uppmaning av kundföretaget ska lämna ett intyg som försäkrar att de uppgifter man lämnat om företagets rutiner och kontroller är riktiga. Uppsatsförfattarna tror dock att det kommer att dröja flera år innan vi ser en ökning av dessa intyg och utlåtanden som beskriver redovisningsbyråns interna kontroll, då det finns en stor motvilja bland små företag, revisorer som reviderar dessa företag och redovisningsbyråer att omge sig med mer byråkrati.    </p>

Det finns idag en stark trend bland företag att outsourca hela eller delar av sin ekonomi-funktion, det vill säga att anlita en extern redovisningsbyrå. Sveriges Redovisningskonsulters Förbund, SRF, har idag 4 500 auktoriserade redovisningskonsulter som medlemmar. Dessa anlitas av mer än 200 000 företag. Denna ökande trend har givit upphov till en helt ny och unik problematik kring hur granskningen av dessa företag ska gå till. Det finns i dagsläget en revisionsstandard, RS 402: Revisorns övervägande vid revision av företag som anlitar servicebyråer, som föreskriver att revisorn ska ta hänsyn till hur redovisningsbyrån påverkar företagens redovisningssystem och interna kontroll.   Uppsatsen är en kvalitativ flerfallsstudie vars syfte är att undersöka vilka ställningstaganden revisorn ställs inför vid revision av företag som outsourcar ekonomifunktionen. Enligt uppsatsens utredningsmodell är revisorns viktigaste ställningstagande huruvida utlagda funktioner är väsentliga för företagets interna kontroll över finansiell rapportering. Om de bedöms väsentliga ska revisionsbevis i form av en RS 402 inhämtas eller då detta saknas test av uppdragstagarens kontroller genomföras. Den empiriska undersökningen visar dock att de revisorer som arbetar med små företag bedömer redovisningskonsultens kunskaper vara det viktigaste ställningstagandet. Få av dessa revisorer har kommit i kontakt med RS 402 i det praktiska arbetet.   En ny revisionsstandard på området, ISAE 3402, håller dock på att utarbetas av International Auditing and Assurance Standards Board (IAASB) och förväntas införas tidigast under hösten 2009. Uppsatsen utreder även hur revisionsprocessen kommer att påverkas av införandet av den nya standarden. Den största förändringen i jämförelse med RS 402 förväntas bli att ledningen av servicebyrån på uppmaning av kundföretaget ska lämna ett intyg som försäkrar att de uppgifter man lämnat om företagets rutiner och kontroller är riktiga. Uppsatsförfattarna tror dock att det kommer att dröja flera år innan vi ser en ökning av dessa intyg och utlåtanden som beskriver redovisningsbyråns interna kontroll, då det finns en stor motvilja bland små företag, revisorer som reviderar dessa företag och redovisningsbyråer att omge sig med mer byråkrati.

Human Epidermal Growth Factor Receptor 2 (HER-2/neu) is a breast tumor antigen (Ag) commonly overexpressed in 30% of breast cancer cases. Both HER-2/neu-targeted DNA-based and transgene modified dendritic cell (DC)-based vaccines are potent elements in eliciting HER-2/neu specific antitumor immune responses; however, there has been no side-by-side comparison of these two different immunization methods. We utilized an in vivo murine tumor model expressing the rat neu Ag to compare the immunization efficacy between DC transduced with replication-deficient adenovirus containing neu (AdVneu), to form DCneu, and plasmid DNA (pcDNA) vaccine. DCneu displayed an upregulation of immunologically important molecules and inflammatory cytokines expression such as IL-6 that partially mediated conversion of the regulatory T (Tr) cell suppression. Wildtype FVB/N mice immunized with DCneu induced stronger HER-2/neu-specific humoral and cellular immune responses compared to plasmid DNA immunized mice. Furthermore, mice immunized with DCneu remained completely protected from tumor challenge compared to partial or no protection observed in DNA immunized mice in two tumor animal models. In FVBneuN transgenic mice, which develop spontaneous breast tumors at 4-8 months of age, DCneu significantly delayed tumor onset when immunization conducted in mice at a younger age. Taken together, we demonstrated that a HER-2/neu-gene modified DC vaccine is more potent than a plasmid DNA vaccine in inducing neu specific immune responses resulting in greater protective and preventative effects in the tumor models examined. <p>In another study, we examined the use of a DC-based cancer vaccine involving the phagocytosis of apoptotic tumor cells expressing heat shock protein 70 (HSP70). The dual role of HSP70, as an antigenic peptide chaperone and danger signal, makes it especially important in DC-based vaccination. In this study, we investigated the impacts of apoptotic transgenic MCA/HSP tumor cells expressing HSP70 on DC maturation, T cell stimulation and overall vaccine efficacy. We found that DC with phagocytosis of MCA/HSP in the early phase of apoptosis expressed more peptide-major histocompatibility class (pMHC) I complexes, stimulated stronger cytotoxic T lymphocytes (CTL) responses and induced greater immune protection against MCA tumor cell challenge, compared to mice immunized with DC that phagocytosed MCA/HSP cells in the late phase of apoptosis. Taken together, our data demonstrated that HSP70 expression on apoptotic tumor cells stimulated DC maturation and DC with phagocytosis of apoptotic tumor cells expressing HSP70 in early phase of apoptosis more efficiently induced tumor-specific CTL responses and immunity than DC with phagocytosis of apoptotic tumor cells in late phase of apoptosis. <p>Overall, we have examined variations in designing DC-based cancer vaccines in two completely different model systems. Taken together, our results may have an important impact in designing DC-based antitumor vaccines.

Human Epidermal Growth Factor Receptor 2 (HER-2/neu) is a breast tumor antigen (Ag) commonly overexpressed in 30% of breast cancer cases. Both HER-2/neu-targeted DNA-based and transgene modified dendritic cell (DC)-based vaccines are potent elements in eliciting HER-2/neu specific antitumor immune responses; however, there has been no side-by-side comparison of these two different immunization methods. We utilized an in vivo murine tumor model expressing the rat neu Ag to compare the immunization efficacy between DC transduced with replication-deficient adenovirus containing neu (AdVneu), to form DCneu, and plasmid DNA (pcDNA) vaccine. DCneu displayed an upregulation of immunologically important molecules and inflammatory cytokines expression such as IL-6 that partially mediated conversion of the regulatory T (Tr) cell suppression. Wildtype FVB/N mice immunized with DCneu induced stronger HER-2/neu-specific humoral and cellular immune responses compared to plasmid DNA immunized mice. Furthermore, mice immunized with DCneu remained completely protected from tumor challenge compared to partial or no protection observed in DNA immunized mice in two tumor animal models. In FVBneuN transgenic mice, which develop spontaneous breast tumors at 4-8 months of age, DCneu significantly delayed tumor onset when immunization conducted in mice at a younger age. Taken together, we demonstrated that a HER-2/neu-gene modified DC vaccine is more potent than a plasmid DNA vaccine in inducing neu specific immune responses resulting in greater protective and preventative effects in the tumor models examined. <p>In another study, we examined the use of a DC-based cancer vaccine involving the phagocytosis of apoptotic tumor cells expressing heat shock protein 70 (HSP70). The dual role of HSP70, as an antigenic peptide chaperone and danger signal, makes it especially important in DC-based vaccination. In this study, we investigated the impacts of apoptotic transgenic MCA/HSP tumor cells expressing HSP70 on DC maturation, T cell stimulation and overall vaccine efficacy. We found that DC with phagocytosis of MCA/HSP in the early phase of apoptosis expressed more peptide-major histocompatibility class (pMHC) I complexes, stimulated stronger cytotoxic T lymphocytes (CTL) responses and induced greater immune protection against MCA tumor cell challenge, compared to mice immunized with DC that phagocytosed MCA/HSP cells in the late phase of apoptosis. Taken together, our data demonstrated that HSP70 expression on apoptotic tumor cells stimulated DC maturation and DC with phagocytosis of apoptotic tumor cells expressing HSP70 in early phase of apoptosis more efficiently induced tumor-specific CTL responses and immunity than DC with phagocytosis of apoptotic tumor cells in late phase of apoptosis. <p>Overall, we have examined variations in designing DC-based cancer vaccines in two completely different model systems. Taken together, our results may have an important impact in designing DC-based antitumor vaccines.

The term &#039 / Costitutional Democracy&#039 / is characterized by an underlying conceptual tension between the rule of law and populSar sovereignty. This is reflected in the controversy surrounding the judicial review of legislation in contemporary political systems. In this thesis, the development of the idea of &#039 / governmernt under law&#039 / in political thought, contemporary debates on the doctrine of judicial review and normative relation between law and politics is analyzed. It is concluded that both &#039 / constitutionality&#039 / and &#039 / popular sovereignty&#039 / are essentil to modern democracy. Yet, it might be problematic to disassociate constitutional law from ordinary politics, since the latter is the principal means through which a polity shapes its future.