The construction industry has an increased focus on using sustainable methods to reach a more sustainable society but is still lacking the social aspect of sustainability. The belief is that this aspect has to be a natural part in construction projects to successfully plan and develop sustainable societies. A method to achieve this could be the use of Social Impact Assessment (SIA), a method frequently used in other countries such as U.S, Australia and Canada. The aim with the thesis is to investigate how this method can be used in a Swedish context, but also how the public in the best manner can be involved in decisions that affect them. To complement the theory with empirical findings a case study is done within Järvalyftet, one of the biggest redevelopment projects in the Stockholm region at the moment. A SIA deals with several areas and issues and is therefore complex to perform in an efficient way. It is consequently important to create a team with mixed disciplines to be able to manage the work and face the different problems in the best possible way. The thesis indicates that public involvement is of major importance to create an acceptance for the planned project among the affected parties in order to reduce both the timeframe and the costs of the project. Further, the thesis indicates that public involvement early on in a project facilitates for the affected people to deal with changes and trade-offs resulting by the project. / Byggbranschen har idag ett större fokus på att använda hållbara metoder i byggandet för att på så sätt nå ett mer hållbart samhälle, men saknar fortfarande fokus på den sociala aspekten inom hållbarhet. För att lyckas med att planera och bygga hälsosamma och hållbara samhällen måste de här aspekterna bli en naturlig del i byggprojekten. En metod för att lyckas med detta kan vara användandet av Social Konsekvensbeskrivning, en metod som ofta används i länder som USA, Australien och Canada. Syftet med detta examensarbete är att undersöka hur denna metod kan användas, men också hur allmänheten på bästa sätt kan bli involverade i beslut som berör dem själva. För att komplettera teorin som använts i arbetet har en case study gjorts inom Järvalyftet, ett av dagens största ombyggnadsprojekt i Stockholmsområdet. En SKB berör många olika områden och frågor och är därför en komplex process att genomföra. Det är följaktligen viktigt att skapa en grupp med varierande yrkesdiscipliner för att hantera arbetet och möta de olika problemen på bästa möjliga sätt. Arbetet visar på att allmänhetens deltagande är av stor betydelse för att skapa förankring bland berörda parter då ett projekt planeras, för att på så sätt minska både projektets tidsram och kostnad. Vidare visar även arbetet att involvering av allmänheten i ett tidigt skede av projektet underlättar för de berörda att hantera de förändringar och avvägningar som projektet medför.

This thesis describes and compares the practices of social impact assessments in Finland, Norway and Sweden. How are social impacts, as caused by any planned intervention, assessed in the countries? How do the countries' practices relate to the international theory and practice? What are the differences, and/or similarities, between the countries? SIA is a procedure of assessing and estimating potential social impacts as caused by some kind ofplanned intervention. The origin of SIA is commonly traced back to the introduction of environmental impact assessment (EIA). However, it has not won the same recognition as its cousin EIA. Since social aspects often are complex and thus difficult to measure and estimate, SIA can be used as a procedure to not only cope with quantitative aspects but also qualitative. Since EIA was introduced into legislation in Europe through the European Council, the Nordic countries have gradually introduced EIA, and impact assessment (IA), in their national legislation. There has not been any introduction of SIA per se in the legislation, however, assessment of social impacts are more or less included in the legislation covering EIA and IA. This thesis shows that SIA, in practice, is used to a differing extent in the countries and that there are some differences in what social impacts comprises and how they are assessed. In Norway the more overall and general IA is used including both biophysical impacts and social impacts, where the social impacts are de$ned and assessed in a rather quantitative way compared to the other two countries. In Finland and Sweden, SIA, as defined in the international theory and practice, is used to some extent. However, the practice in Sweden is not as widespread as in Finland and Norway, where social aspects and impacts seems to be more integrated in impact assessments. / Den här uppsatsen beskriver och jämför användningen i praxis av social impact assessments, sociala konsekvensbeskrivningar (SKB), i Finland, Norge och Sverige. Hur utreds sociala konsekvenser, som uppkommit till följd av en planerad aktivitet, i de olika länderna? Hur relaterar ländernas praxis med den internationella teorin och praxisen? Vilka är skillnaderna och/eller likheterna mellan länderna? SKB är ett tillvägagångssätt för att utreda och uppskatta potentiella sociala konsekvenser som uppkommit till följd av en planerad aktivitet. SKB brukar vanligtvis sägas ha sitt ursprung i och med introduktionen av environmental impact assessment, miljökonsekvensbeskrivningen (MKB), men har inte fått samma genomslag som sin kusin MKB:n. Eftersom sociala aspekter ofta är komplexa och invecklade, och därför svåra att mäta och uppskatta, kan SKB användas som en metod att hantera, inte bara kvantifierbara aspekter, utan även kvalitativa. Sedan MKB introducerades i europeisk lagstiftning genom Europeiska rådet har de nordiska länderna gradvis infört MKB, och konsekvensbeskrivningar, i deras nationella lagstiftning. SKB per se har inte introducerats i den nationella lagstiftningen, men utredningar av sociala konsekvenser är mer eller mindre en del av lagstiftningen för MKB och konsekvensbeskrivningar. Denna uppsats visar att SKB används i skiftande utsträckning i praxis i länderna och att det finns skillnader i vad sociala konsekvenser tycks omfatta och hur de utreds. I Norge används den mer övergripande och generella termen konsekvensbeskrivning vilken inkluderar både miljömässiga och sociala konsekvenser där de sociala konsekvenserna utreds och definieras i relativt kvantitativa termer jämfört med de andra länderna. I Finland och Sverige används SKB, som det definieras i den internationella teorin och praxisen, till viss del. Men den svenska praxisen är inte lika omfattande som i Finland och Norge där sociala aspekter och konsekvenser verkar vara mer integrerade i konsekvensbeskrivningar.

La scoliose idiopathique de l’adolescent (SIA) est définie comme une courbure de la colonne vertébrale supérieure à 10 degrés, qui est de cause inconnue et qui affecte de façon prépondérante les adolescents. Des études précédentes sur des modèles murins ont démontré une inactivation partielle du gène Pitx1. Cette inactivation partielle provoque une déformation spinale sévère lors du développement des souris Pitx1+/-, ce qui est grandement similaire au phénotype de la SIA. En se basant sur ces observations, nous postulons que la perte de fonction de Pitx1 pourrait avoir un rôle dans la SIA et pourrait être régulée par des mécanismes moléculaires spécifiques. En effet, des études faites sur l’expression de Pitx1 révèlent une perte de son expression dans les ostéoblastes dérivés de patients SIA au niveau de l’ARNm. Nous émettons l’hypothèse que la perte de Pitx1 dans la SIA pourrait être déclenchée par des facteurs hypoxiques puisqu’il est connu que Pitx1 est réprimé par l’hypoxie et que HIF-2 alpha est surexprimés dans les ostéoblastes des patients SIA même dans des conditions normoxiques. De plus, nous avons découvert une mutation dans le domaine ODD des HIF-1 alpha chez certains patients SIA (3,1%). Une fonction connue de ce domaine est de stabiliser et d’augmenter l’activité transcriptionnelle de HIF-1 alpha dans des conditions normoxiques. Nous avons confirmé, par la technique EMSA, l’existence d’un élément de réponse fonctionnel à l’hypoxie au niveau du promoteur de Pitx1. Cependant, des co-transfections avec des vecteurs d’expression pour HIF-1 alpha et HIF-2 alpha, en présence de leur sous-unité beta ARNT, ont conduit à une activation du promoteur de Pitx1 dans la lignée cellulaire MG-63 ainsi que dans les ostéoblastes des sujets contrôles. Il est intéressant de constater qu’aucune activité du promoteur de Pitx1 dans les ostéoblastes SIA n’a été observée, même après la co-expression de HIF-2 alpha et ARNT, confirmant le fait que l’expression de Pitx1 est abrogée dans la SIA. Dans l’ensemble, nos résultats démontrent un rôle important de Pitx1 dans la SIA et une possible régulation par des facteurs hypoxiques. / Adolescent Idiopathic Scoliosis is a lateral curvature of the spine greater than 10 degrees, with an unknown cause, affecting primarily adolescents. Previous mouse model studies showed that partial inactivation of Pitx1 gene resulted in the development of severe spinal deformities in Pitx1 +/- mice, which is strikingly similar to the AIS phenotype. Based on this observation, we postulated that loss of Pitx1 function might have a role in AIS and could be regulated through specific molecular mechanisms. Indeed, expression studies revealed a loss of Pitx1 expression in osteoblasts derived from AIS patients, at the mRNA level. We hypothesized that the loss of Pitx1 in AIS could be triggered by hypoxic factors, since Pitx1 is known to be repressed by hypoxia and that HIF-2 alpha was up regulated in AIS osteoblasts even under normoxic conditions. Also, we found a mutation in the ODD domain of HIF-1 alpha in some AIS patients (3.1%), which is known to stabilize and enhance HIF-1 alpha transcriptional activity in normoxic conditions. We confirmed through EMSA the existence of a functional hypoxia response element on Pitx1 promoter. However, co-transfection assays with HIF-1 alpha and HIF-2 alpha expression vectors in the presence of their beta subunit ARNT led to the activation of Pitx1 promoter in human osteoblast cell line MG-63 cells and osteoblasts from control subjects. Interestingly, no Pitx1 promoter activity was observed in AIS osteoblasts, even after the co expression of HIF2 alpha and ARNT, consolidating the fact that Pitx1 expression is abrogated in AIS. Taken together, our findings show an important role for Pitx1 in AIS and hypoxic factors could be one of its regulators.

Made available in DSpace on 2015-04-14T14:26:50Z (GMT). No. of bitstreams: 1 381130.pdf: 466181 bytes, checksum: 1a958c723cd9f7520bfd72e87a3aaa3a (MD5) Previous issue date: 2006-04-24 / Neste trabalho ? estudada a rela??o emp?rica entre o desenvolvimento financeiro e o crescimento econ?mico. Foram estudados dois conjuntos de pa?ses, no per?odo 1987-2000; o primeiro formado por 20 pa?ses da Am?rica Latina e o segundo formado pelos primeiros acrescidos de 13 pa?ses da ?sia. Como proxies do desenvolvimento financeiro utilizou-se o grau de aprofundamento financeiro, medido pela rela??o M2/PIB, e o grau de intermedia??o financeira, medido pelo cr?dito ao setor privado/PIB, em seus valores m?dios e iniciais. Os valores iniciais foram utilizados para verificar se estas proxies em seus valores iniciais seriam um bom preditor do crescimento econ?mico. O m?todo econom?trico utilizado foi uma an?lise de cross-section. Os resultados mostraram uma rela??o positiva e significativa para as duas vari?veis em valores m?dios para a Am?rica Latina. Em valores inicias, no caso da Am?rica Latina as vari?veis de desenvolvimento financeiro n?o mostraram-se como bons preditores do crescimento econ?mico. Para a amostra ampliada, o grau de aprofundamento do sistema financeiro n?o apresentou uma rela??o significativa com o crescimento econ?mico, tanto em valores m?dios como em valores iniciais. O grau de intermedia??o financeira apresentou uma rela??o positiva e significativa com o crescimento econ?mico em valores m?dios e valores iniciais, sugerindo uma rela??o de causalidade, indo do desenvolvimento financeiro para o crescimento econ?mico.

Made available in DSpace on 2015-04-14T14:47:47Z (GMT). No. of bitstreams: 1 383739.pdf: 885756 bytes, checksum: ab703c5919c69f12e4f776b9a7dc6fc5 (MD5) Previous issue date: 2006-08-09 / O presente estudo tem por escopo analisar a problem?tica do desrespeito ? pessoa humana e o direito de morrer com dignidade, atrav?s de uma discuss?o interdisciplinar, que culminar? com a abordagem do enquadramento na esfera criminal da a??o ou omiss?o perpetrada pelo agente que pratica a eutan?sia. Consoante ? cedi?o os recursos tecnol?gicos da medicina atual permitem o prolongamento da vida em muitas situa??es que, at? um passado n?o muito distante, determinavam a morte do paciente. Houve uma mudan?a no processo de morrer. As leituras, as reflex?es e os confrontos com a morte nos hospitais de hoje, altamente equipados com tecnologia sofisticada e f?rmacos poderosos, s?o parte de um todo que procura resgatar a vida a qualquer custo. Atualmente, pode-se manter indeterminadamente um paciente biologicamente vivo, mas ser? que a vida se resume aos sinais biol?gicos? O que se vislumbra discutir ? se o prolongamento artificial da vida humana deve se sobrepor ? dignidade humana compulsoriamente, mesmo quando envolve sofrimento para o doente, para os que lhe s?o pr?ximos e comprometimento do respeito devido ao ser humano. O trabalho apresenta a eutan?sia - compreendida como a boa morte - e modalidades an?logas, buscando aferir em quais situa??es comporta o prosseguimento ou implanta??o de tratamentos m?dicos e em quais eles se tornam desnecess?rios e ineficazes, consubstanciando-se em obstina??es terap?uticas. Nesse diapas?o, ap?s expor os conceitos pertinentes ?s diversas acep??es de eutan?sia, objetivando contextualizar o leitor nas quest?es que ser?o apresentadas, abordar-se-? os princ?pios de bio?tica que, dever?o ser analisados na rela??o m?dico-paciente, tais como: benefic?ncia, n?o malefic?ncia, Justi?a e respeito ? autonomia do paciente; todos discutidos a luz da dignidade da pessoa humana. Posteriormente, ser?o perquiridos os efeitos jur?dicos decorrentes da postura a ser adotada em face da tens?o existente entre o direito ? vida e o respeito devido ? dignidade da pessoa humana. Por derradeiro, com fulcro na postura adotada em face da dignidade da pessoa humana analisar-se-? o reflexo jur?dico penal da conduta realizada pelo autor da eutan?sia nas modalidades que configuram a "boa morte", "morte doce", " morte suave", isto ?, sem dores e sofrimentos.

Made available in DSpace on 2015-04-14T13:32:36Z (GMT). No. of bitstreams: 1 401600.pdf: 531587 bytes, checksum: b25d1bacf7575790cf35d1987e65faf1 (MD5) Previous issue date: 2008-03-26 / Objetivos: analisar as atitudes m?dicas nas ?ltimas 48 horas de vidas de pacientes adultos que morrem em Unidade de Tratamento Intensivo (UTI), as decis?es de Reanima??o Cardio-Pulmonar (RCP) e de Limita??o do Suporte de Vida (LSV), os fatores determinantes, seus respons?veis e registros, o diagn?stico de ME e a conduta para os n?o doadores. M?todos: estudo observacional retrospectivo com an?lise dos prontu?rios m?dicos de tr?s UTI de Porto Alegre (Brasil), de 2004 e 2005. Intensivistas foram treinados para preencher o protocolo e registrar os dados demogr?ficos e todo o tratamento m?dico oferecido nas ultimas 48 horas de vida. Foram analisados dados gerais de cada paciente (idade, sexo, tempo de interna??o hospitalar e de UTI), do diagn?stico principal (motivo da interna??o hospitalar e em UTI, disfun??es org?nicas das ?ltimas 48 horas de vida, causas dos ?bitos, diagn?stico de morte encef?lica e doa??es) e das condutas (RCP ou LSV). A participa??o dos familiares e dos m?dicos e seus registros foram criteriosamente estudados. Resultados: 710 mortes identificadas, com perda de 10,5%. 636 ?bitos analisados, 87 foram submetidos a RCP (14,0%): mais jovens, menor tempo de interna??o hospitalar e em UTI (p< 0,001), quando comparados aos 538 pacientes submetidos a LSV (86%). Desses, 75% tiveram ONR, com tratamento pleno at? a morte. 67% dos prontu?rios sem registros dessas decis?es. A ME ? rara (11/636), os n?o doadores s?o mantidos com ventila??o e vasopressores at? a PCR. Apenas 25% das fam?lias partilhou dessas decis?es com a equipe m?dica. Conclus?es: A LSV ? pratica dominante em UTI, com escassos registros, sendo a ONR sua forma mais comum, com tratamento pleno mantido at? a morte. A ME e as doa??es s?o raras, os n?o doadores s?o mantidos com vasopressores e ventila??o at? a PCR. Tr?s de cada quatro fam?lias n?o participam dessas decis?es.

A alta competitividade e os avanços tecnológicos propiciaram o surgimento de um novo modelo de terceirização de Tecnologia de Informação (TI), os Provedores de Serviços de Aplicativos (ASP - Application Service Providers). A proposta do modelo ASP é a comercialização de aplicativos de software como serviço. A satisfação dos clientes está diretamente relacionada à qualidade do serviço prestado. Para garantir que sejam fornecidos serviços com qualidade, é fundamental a adoção dos Acordos dos Níveis de Serviços (SLA - Service Levei Agreements) como mecanismo de controle. No entanto, são escassas as informações formalizadas que venham a contribuir com a especificação desses acordos. Propondo-se a contribuir com a compreensão de SLA para ASP, apresenta-se uma pesquisa exploratória do conceito de SLA para ASP, de modelos de qualidade e dos fatores de qualidade a serem considerados nos SLA para garantir a qualidade dos serviços prestados. / lhe current competitiveness of the global market and the continuous technological evolution pushed the risen of a new model of Information Technogy Outsourcing, the Application Service Providers (ASP). The ASP modelproposes the remote delivery of software as a service. Therefore, customers\' satisfaction is strictelly related to the quality of ser\\>ice delivered. It is highly recommended the adoption of Service Levei Agreement (SLA) as a control mechanism to assure such quality of service. However, there is a lack of formalized statements regarding the specification of these agreements. As a matter of contribution for the compreension of the SLA for ASP, this work introduces an exploratory research of the concep of SLA for ASP, and of the quality models and quality metrics to be considered by the SLA to assure the quality of the services provided.

Made available in DSpace on 2014-12-17T15:39:00Z (GMT). No. of bitstreams: 1 AldaKLS_DISSERT.pdf: 1481522 bytes, checksum: 8814caf0ffdd4e62dedf289add6a9c67 (MD5) Previous issue date: 2012-06-18 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / This research aimed to analyze the dynamics established between the activity of the teacher in Distance Education (DE) and professional gender of teaching, in terms of impact of DE in teacher s usual professional activity. Previous studies showed that one of the central discussions concerning DE refers to the role that the teacher is called to perform. The present research, based on theoretical and methodological assumptions issued from Clinic of Activity, analyzed the impact referred above. This central aim was operationally executed along three main stages: 1) survey study for description of socio-professional profile of teachers working in DE in two universities from Natal (RN-Brazil), 2) clinical analysis of professional activity of teachers working in DE, taking into account four simultaneous levels of psychological constitution and development of human activity: personal, interpersonal, transpersonal and impersonal; 3) analytical focus on transpersonal context in order to understand the influence of pedagogical practice in DE on professional gender of teaching. Documental research, audio recorded voice data and a multiple choice Likert scale questionnaire concerning socio-professional information were used as procedural tools. The qualitative-clinical procedural tool of instruction to the double , firstly proposed by Clinic of Activity research group, was used in order to obtain oral productions concerning professional activity. Data issued from stage 1 (n=70, 28 men and 41 women) was submitted to descriptive and inferential statistical analyzes. 65.7% of the sample worked in a public institution, 30% in a private institution, and 4.3% in public and private institutions. 31.4% of the sample of participants was formed by teachers having a master degree, 28.6% were doctors and 26.3% had degrees of specialists. 54.3% of participants acted as remote tutor, and 44.3% were regents teachers. After descriptive multidimensional cluster analysis, two groups emerged (remote tutors and regents teachers), the most important variables in terms of contributions to this distinction being: professional function, level of graduate formation, level of income, activities and forms of entry in DE. Clinical analysis of data produced by two participant-teachers of each group, issued from instruction to the double technique, was performed. This analysis indicated the existence of different models of distance education. A general concern referring to the need of both taking into account information technology and pedagogical attitudes was detected. On the other hand, participant-teachers considered that participation in DE activities could bring relevant contributions to general professional gender of teaching. . Finally, teachers warned against certain formats of organization of teachers professional activity, as found in the domain of DE, since these activities could promote the intensification and individualization of teachers` work activity, and even the worsening of relations, rather than exchanges and shares through collective bargaining. This process could compromise the renew of the professional gender, by losing its historical roots and diminishing activity possibilities of teachers in their labor context / Estudos apontaram que uma das discuss?es centrais na Educa??o a dist?ncia (EAD) refere-se ao papel que o professor ? convocado a desempenhar. A pesquisa, pautada pelos pressupostos te?rico-metodol?gicos da Cl?nica da Atividade, objetivou analisar a din?mica que se estabelece entre a atividade do professor na EAD e o g?nero profissional docente ao qual ele reporta-se em sua atividade profissional. As etapas do estudo dividiram-se em: 1) mapear o perfil socioprofissional dos professores que atuam na EAD em duas universidades da cidade do Natal (RN); 2) analisar a atividade de trabalho dos professores na EAD, em abordagem cl?nica norteada pelos contextos de desenvolvimento da atividade: pessoal, interpessoal, transpessoal e impessoal; e 3) compreender a influ?ncia da pr?tica pedag?gica na EAD sobre o g?nero profissional docente, enfatizando o contexto transpessoal. Para consecu??o dos objetivos, os instrumentos e procedimentos propostos foram: pesquisa documental, registros audiogr?ficos (representados pela t?cnica da instru??o ao s?sia), e um question?rio socioprofissional. As an?lises estat?sticas descritivas e inferenciais do mapeamento contemplou uma amostra de 70 participantes, sendo 28 homens e 41 mulheres. 65,7% vinculavam-se ? institui??o p?blica, 30% ? institui??o privada e 4,3% ?s institui??es p?blica e privada. 31,4% era mestre, seguido de 28,6% de doutores e 26,3% especialistas. 54,3% exerciam a fun??o de tutor ? dist?ncia e 44,3% eram professores regentes. Ap?s clusteriza??o, apontou-se a exist?ncia de dois grupos (tutor a dist?ncia e professor regente), e as vari?veis mais importantes de distin??o foram: fun??o, titula??o, renda, atividades desenvolvidas e forma de ingresso na EAD. Da etapa cl?nica participaram dois professores representantes de cada grupo. A an?lise da atividade de trabalho apontou a exist?ncia de modelos de EAD distintos, que produziam formatos de trabalhos cuja conformidade com o g?nero profissional docente era reflexo das diferentes formas de vivenciar os espa?os de doc?ncia. Quanto ao alargamento das atividades, destaca-se a necessidade do desenvolvimento tanto de compet?ncias t?cnicas para utilizar as tecnologias de informa??o, quanto das pedag?gicas para pensar as concep??es e os modos de concretiza??o do processo de ensino-aprendizagem na EAD. Aponta-se que as mudan?as que a EAD produziu na atividade dos professores os convocaram a um acesso mais profundo das orienta??es gen?ricas da profiss?o, de modo a contribuir para (re)vitaliza??es do g?nero profissional docente, n?o necessariamente atrelado ao uso do modelo presencial como um guia, pois replicar o modelo presencial para a dist?ncia n?o seria garantia do sucesso da atividade do professor na EAD. Destaca-se, ainda, que o insucesso da atividade tamb?m permite o aceso e a transmiss?o do g?nero profissional. Por fim, alerta-se que certos formatos de trabalho, como nos casos da EAD, preveem intensifica??o e individualiza??o da atividade de trabalho, e, at? mesmo, precariza??o das rela??es, em detrimento de trocas e compartilhamentos entre os coletivos de trabalho. Assim, a revitaliza??o do g?nero fica comprometida, e a amputa??o da hist?ria do coletivo pode materializar-se, de modo a contribuir para atrofiar o raio de a??o do sujeito-trabalhador em seu cen?rio laboral

La scoliose idiopathique de l’adolescent (SIA) est définie comme une courbure de la colonne vertébrale supérieure à 10 degrés, qui est de cause inconnue et qui affecte de façon prépondérante les adolescents. Des études précédentes sur des modèles murins ont démontré une inactivation partielle du gène Pitx1. Cette inactivation partielle provoque une déformation spinale sévère lors du développement des souris Pitx1+/-, ce qui est grandement similaire au phénotype de la SIA. En se basant sur ces observations, nous postulons que la perte de fonction de Pitx1 pourrait avoir un rôle dans la SIA et pourrait être régulée par des mécanismes moléculaires spécifiques. En effet, des études faites sur l’expression de Pitx1 révèlent une perte de son expression dans les ostéoblastes dérivés de patients SIA au niveau de l’ARNm. Nous émettons l’hypothèse que la perte de Pitx1 dans la SIA pourrait être déclenchée par des facteurs hypoxiques puisqu’il est connu que Pitx1 est réprimé par l’hypoxie et que HIF-2 alpha est surexprimés dans les ostéoblastes des patients SIA même dans des conditions normoxiques. De plus, nous avons découvert une mutation dans le domaine ODD des HIF-1 alpha chez certains patients SIA (3,1%). Une fonction connue de ce domaine est de stabiliser et d’augmenter l’activité transcriptionnelle de HIF-1 alpha dans des conditions normoxiques. Nous avons confirmé, par la technique EMSA, l’existence d’un élément de réponse fonctionnel à l’hypoxie au niveau du promoteur de Pitx1. Cependant, des co-transfections avec des vecteurs d’expression pour HIF-1 alpha et HIF-2 alpha, en présence de leur sous-unité beta ARNT, ont conduit à une activation du promoteur de Pitx1 dans la lignée cellulaire MG-63 ainsi que dans les ostéoblastes des sujets contrôles. Il est intéressant de constater qu’aucune activité du promoteur de Pitx1 dans les ostéoblastes SIA n’a été observée, même après la co-expression de HIF-2 alpha et ARNT, confirmant le fait que l’expression de Pitx1 est abrogée dans la SIA. Dans l’ensemble, nos résultats démontrent un rôle important de Pitx1 dans la SIA et une possible régulation par des facteurs hypoxiques. / Adolescent Idiopathic Scoliosis is a lateral curvature of the spine greater than 10 degrees, with an unknown cause, affecting primarily adolescents. Previous mouse model studies showed that partial inactivation of Pitx1 gene resulted in the development of severe spinal deformities in Pitx1 +/- mice, which is strikingly similar to the AIS phenotype. Based on this observation, we postulated that loss of Pitx1 function might have a role in AIS and could be regulated through specific molecular mechanisms. Indeed, expression studies revealed a loss of Pitx1 expression in osteoblasts derived from AIS patients, at the mRNA level. We hypothesized that the loss of Pitx1 in AIS could be triggered by hypoxic factors, since Pitx1 is known to be repressed by hypoxia and that HIF-2 alpha was up regulated in AIS osteoblasts even under normoxic conditions. Also, we found a mutation in the ODD domain of HIF-1 alpha in some AIS patients (3.1%), which is known to stabilize and enhance HIF-1 alpha transcriptional activity in normoxic conditions. We confirmed through EMSA the existence of a functional hypoxia response element on Pitx1 promoter. However, co-transfection assays with HIF-1 alpha and HIF-2 alpha expression vectors in the presence of their beta subunit ARNT led to the activation of Pitx1 promoter in human osteoblast cell line MG-63 cells and osteoblasts from control subjects. Interestingly, no Pitx1 promoter activity was observed in AIS osteoblasts, even after the co expression of HIF2 alpha and ARNT, consolidating the fact that Pitx1 expression is abrogated in AIS. Taken together, our findings show an important role for Pitx1 in AIS and hypoxic factors could be one of its regulators.

Made available in DSpace on 2015-03-13T17:08:14Z (GMT). No. of bitstreams: 1 LeandsonRFL_Ate_ cap6.pdf: 2182746 bytes, checksum: 25783c90c53780b39921fc195504a37c (MD5) Previous issue date: 1998-10-27 / This MSc dissertation presents the results of a research carried out in a 500 km2 area in the N?sia Floresta county. The main goal of the research was to evaluate fault influence on hidrology features of aquifers and lakes, mainly in the Barreiras Group and in the Bonfim lake cluster respectively. The Precambrian crystalline basement is made of Caic? Complex rocks. They are capped by cretaceous sedimentary rocks and by cenozoic sedimentary rocks. Only the latter outcrop in the study area, wheareas the former are described in boreholes. Faults cut across all stratigraphic units and their main trends are NW, NE and E-W, which have been generated by E-W compression. Subordinate N-S trending faults also take place and have been generated by N-S oriented compression. Fault controlled hydrologic features are observed throughout the study area. There are sudden changes in saturated thicknesses of the Barreiras Aquifer due to vertical displacement of the Barreiras Group. The most important underground water source of the Bonfim Lake is related to abrupt thickness changes of the aquifer. In addition, the main faults control the underground drainage network and, probably, change in direction of equipotential surfaces seen on the potenciometric map. Regarding the surface hydrologic features, faults also control river and stream channels, as well as lake origin and shapes. The Bonfim Lake, in particular, has its peculiar shape, which follows NW and NE lineaments, and origin related to faulting and probably underground carstics processes / Esta disserta??o apresenta os resultados de uma pesquisa desenvolvida numa ?rea com cerca de 500 km2, a maior parte situada no munic?pio de N?sia Floresta-RN. O objetivo central ? avaliar as influ?ncias da estrutura??o regional na hidrologia dos terrenos sedimentares cenoz?icos, com destaque especial para o Aq??fero Barreiras e o sistema lacustre do Bonfim. Foi adotado uma metodologia fundamentada no emprego de t?cnicas geof?sicas (gravimetria e eletro-resistividade) e estruturais. A estratigrafia da ?rea ? constitu?da pelo embasamento cristalino Pr?-Cambriano, correlato ao Complexo Caic?, sotoposto a sedimentos cret?cicos e capeados por unidades estratigr?ficas cenoz?icas, na qual apenas estas ?ltimas s?o aflorantes. O arcabou?o tectono-estrutural ? formado por uma complexa estrutura??o regional, caracterizada em tr?s dire??es principais: NW, NE e E-W, aproximadamente, al?m de uma quarta dire??o, menos expressiva, com orienta??o geral N-S. Esta estrutura??o representa o resultado da atua??o de um campo de tens?es com compress?o e distens?o m?ximas em E-W e N-S, respectivamente, ? exce??o do trend N-S que est? associado a uma compress?o N-S. As conseq??ncias dos falhamentos na hidrologia subterr?nea s?o evidenciadas, principalmente, pela exist?ncia de varia??es bruscas da espessura saturada do Aq??fero Barreiras, decorrente do deslocamento vertical de blocos estruturais nestes falhamentos. Em particular, a oeste da Lagoa do Bonfim, mostrou-se que a principal frente de alimenta??o subterr?nea da lagoa est? associada a um aumento brusco da espessura do aq??fero decorrente dos rejeitos verticais de duas falhas. As estruturas s?o respons?veis ainda pelos limites da drenagem subterr?nea e, provavelmente, por inflex?es das superf?cies equipotenciais no mapa potenciom?trico da ?rea. No ?mbito da hidrologia superficial, os falhamentos condicionam os cursos de rios e riachos (anomalias hidrogr?ficas), limites superficiais e padr?es da rede de drenagem, assim como as formas e g?neses das principais lagoas da ?rea. A Lagoa do Bonfim, particularmente, possui sua g?nese e evolu??o relacionada ? a??o de duas estruturas, ressaltada pela forma ex?tica de seu espelho d ?gua (alongado segundo as dire??es NW e NE das referidas falhas), somada ? prov?vel intera??o com processos c?rsticos na seq??ncia carbon?tica mesoz?ica