Thesis (M. Arch.)--Massachusetts Institute of Technology, Dept. of Architecture, 1982. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND ROTCH / Includes bibliographical references. / Recent technological changes in railroads, mergers, major shifts in urban land use patterns, and declining rail passenger travel has resulted in a surplus of urban rail lands. These lands represent a significant resource for land poor cities. An unparalleled opportunity exists for major new intervention without the usual adverse effects of land assemblage and so called "urban renewal". This work is an urban design study for a 22 acre rail site and 15 acres of adjacent waterfront land in Tacoma, Washington. The site, including Union Station and its yards, is on the edge of Tacoma's central business district. Union Station represents the largest assembled parcel of developable land in the downtown area. An attempt is made to illustrate a possible site use scenario which reflects the divergent and often conflicting goals of various differing interests. / by Jeffrey David Rhoads. / M.Arch.

ALK1 est un récepteur de la famille du TGF-β, principalement exprimé dans les cellules endothéliales. Le ligand physiologique et circulant d'ALK1, BMP9, a été découvert par notre laboratoire en 2007, ce qui a ouvert des possibilités d'étude de la fonction d'ALK1. La première partie de ma thèse a été consacrée à l'analyse fonctionnelle de mutants d'ALK1, retrouvés sur des patients atteints de la maladie de Rendu-Osler de type 2, en réponse à BMP9. Cette étude a permis de : 1) proposer l'haploinsuffisance fonctionnelle comme modèle de la maladie ; 2) développer un test diagnostique pour discriminer les mutations pathogènes des polymorphismes rares, basé sur leur réponse à BMP9 ; 3) d'avoir une meilleure connaissance des acides aminés d'ALK1 importants dans la réponse à BMP9. Un second travail a consisté en la production de la forme mature de BMP9 et du domaine extracellulaire d'ALK1 en vue de l'étude de la structure cristallographique du complexe. L'expression des protéines et leur purification sont en phase d'optimisation. Enfin, un troisième projet consistait en l'analyse du rôle de BMP9 dans l'angiogenèse in vivo. La neutralisation de BMP9 par deux stratégies distinctes induit une augmentation de la densité vasculaire dans la rétine de la souris. Le mécanisme est en cours d'investigation. / ALK1 is a TGF-β family receptor, mainly expressed on endothelial cells. The physiologic and circulating ligand of ALK1, BMP9, was discovered by our laboratory in 2007, which opened opportunities for studying the function of ALK1. The first part of my thesis was on the functional analysis of ALK1 mutants from HHT-2 patients in response to BMP9. This study allowed us to: 1) propose functional haploinsufficiency as a model for HHT-2; 2) develop a diagnostic tool to discriminate pathogenic mutations from rare polymorphisms, based on their BMP9 response; 3) increase our knowledge of important amino acids in ALK1 for the BMP9 response. A second work was on the production of the mature form of BMP9 and of the extracellular domain of ALK1 in order to study the crystallographic structure of the complex. The expression of these proteins and their purification are in optimization phase. Lastly, a third project was on the analysis of the role of BMP9 in angiogenesis in vivo. Neutralization of BMP9 using two strategies induces an increase of the vascular density of the retina in mouse. Mechanism of action is under investigation.

Thesis. 1978. M.Arch--Massachusetts Institute of Technology. Dept. of Architecture. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND ROTCH. / Bibliography: leaves 120-121. / M.Arch

Thesis (M. Arch.)--Massachusetts Institute of Technology, Dept. of Architecture, 1980. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND ROTCH. / Includes bibliographical references (p. 111-112). / Through massing , scale, craftsmanship, and their traditional role, church buildings are valuable to the city. They play an important role in the cognitive and formal ordering of the city. They are important to the temporal contect of the city. As the site of milestone events in many people's lives, or as symbols of these events in others' lives, church buildings are important for the collective memory. The grand scale of the church space combined with careful small scale detailing, make it a place with qualities that are rare in the daily life of most people. Because of their importance to the city opportunities and methods to reuse church buildings should be found if the buildings are abandoned by their congregations. Uses should be found that are sympathetic to the spirit and the form of the building. The forms in church architecture are powerful enough that they can survive extensive, yet sensitive, new construction to accommodate a new use and allow the place to read as a new building that was once a church. In order to allow the building to provide a temporal context to the present, when the building is given a new use it must also be given a new image. The elements of the image of a church must be analyzed to discover those which are the most powerful and how they may be changed to allow revealing juxtapositions that say, "this building was a church but is one no longer." In changing the image of the church building, care must be taken not to destroy those qualities which made attempting its reuse worthwhile. These issues are investigated in a series of case studies of reused churches. Several new issues in the redesign of church buildings were discovered through the case studies. The result is a set of observations and conclusions that are a synthesis of the real and the ideal. / by Laurie Putscher. / M.Arch.

The timely remodeling of the cervix from a mechanical barrier into a soft, compliant structure, which dilates in response to uterine contractions is crucial for the safe delivery for a term baby. A cervix which softens too early in the pregnancy is implicated in spontaneous preterm births (sPTB). Currently, 15 million babies are affected by PTB annually, early diagnosis is difficult, and 95% of all PTBs are unmanageable by available therapies. These statistics highlight the need to better understand the biological processes involved in cervical remodeling and its downstream effects on material properties. To address this need, we propose the development of a hormone-mediated material constitutive model for the cervix where steroid hormone actions on key tissue constituents are incorporated into a microstructure-inspired material model. As the first steps towards the development of this model, the main objective of this dissertation work is to understand the key structure-mechanical function relationships involved in pregnancy. To understand cervical material property changes, the equilibrium swelling and tensile response of the nonpregnant and pregnant mouse cervix is measured, a porous fiber composite material model is proposed, and the model is fit to the mechanical data then validated. To better understand key tissue constituents involved, the evolution of intermolecular collagen crosslinks is determined in normal pregnancy and the role of the small proteoglycan, decorin, and elastic fiber structure on cervical mechanical function is investigated. The results presented here demonstrate that a porous, continuously distributed fiber composite model captures the three-dimensional mechanical properties of the nonpregnant and pregnant cervix. The material property changes of the cervix in a 19-day mouse gestation is described as a four order of magnitude decrease in the parameter associated with the fiber stiffness. We provide quantitative evidence to demonstrate the role of collagen crosslinks on tissue softening in the first 15 days, but not in the latter stages of a mouse pregnancy. A role of elastic fiber structure on cervical mechanical function is demonstrated, as well as distinct roles of estrogen on elastic fiber structure and progesterone on collagen fibril structure. Lastly, an analysis of the time-dependent response of cervices from nonpregnant, normal pregnant, and induced PTB mice are presented. This dissertation concludes by reviewing the presented data within the context of the proposed framework to suggest future directions towards its development.

Thesis. 1977. M.Arch.--Massachusetts Institute of Technology. Dept. of Architecture. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND ROTCH. / Bibliography : leaves 88-89. / by Philip G. Freelon. / M.Arch.

Estudos epidemiológicos têm demonstrado que a exposição à fumaça de cigarro - ativa ou passiva - está altamente correlacionada ao agravamento e severidade do quadro asmático, que inclui inflamação, hiperresponsividade e remodelamento pulmonar. Os modelos experimentais que conjugam asma e tabagismo, em geral, abordam apenas alguns aspectos isolados desta complexa relação, e carecem de elucidação sobre as possíveis interrelações existentes. Neste modelo experimental, a proposta foi analisar os efeitos da coexposição de curta duração à fumaça de cigarro - do tipo \"mainstream\" - e alérgeno em camundongos previamente sensibilizados, focando as características fisiopatológicas e funcionais da asma ao final de três semanas. Os resultados demonstraram que o grupo coexposto à OVA e fumaça de cigarro (OF) apresentou diminuição do número total e diferencial de todas as células no lavado broncoalveolar, bem como da expressão celular de INF-gama e IL-4 quando comparados ao grupo OVA. Por outro lado, os parâmetros relativos ao remodelamento pulmonar parecem ser afetados de maneira oposta, demonstrado pelo aumento substancial do conteúdo de colágeno e pela expressão celular de MMP9 e TGF-? no grupo OF. A responsividade pulmonar, por sua vez, apresentou elastância aumentada nos animais com inflamação pulmonar alérgica crônica em comparação aos demais grupos, sugerindo uma correlação entre o número de eosinófilos e a resposta mecânica observada. A atividade de certos componentes específicos da fumaça de cigarro parece influenciar o comportamento das alças regulatórias no processo de inflamação, como sugerido pela expressão celular aumentada de IL-10 nos grupos expostos ao fumo. Conclui-se, portanto, que neste modelo experimental, a variedade de elementos químicos presentes na fumaça do cigarro pode afetar de maneira diferenciada os aspectos da inflamação pulmonar alérgica crônica em camundongos. / Several epidemiologic studies have shown that active as well passive smoking is positively associated with asthma severity, including inflammation, hiperresponsiveness and lung remodeling. Experimental models that conjugate asthma and smoking usually approach isolated aspects of this complex relation and more elucidation is needed about possible mechanisms involved. In this experimental model, the proposal was analyze the effects of short-term cigarette smoke - mainstream - on animals previously sensitized, pointing on physiological and functional characteristics of asthma during three weeks. Results demonstrated coexposed group to allergen and cigarette smoke (OVA+CS group) showed a decrease of total and differential number of all cells of bronchoalveolar lavage, as well cellular expression of INF-gamma and IL-4 when compared to OVA group. On the other hand, parameters related to lung remodeling seemed to be affected in opposite way, demonstrated by an increase of collagen content and cellular expression of MMP9 and TGF-beta of OVA+CS group. Pulmonary responsiveness was increased in tissue elastance in animals with chronic allergic pulmonary inflammation when compared to all groups, suggesting a correlation between eosinophils number and mechanical response observed. The activity of specific cigarette smoke components may influence the behavior of regulatory loops in inflammatory process, as showed by increased cellular expression of IL-10 in cigarette smoke exposed groups. In conclusion, in this experimental model the variety of chemical elements of cigarette smoke may affect in distinct ways aspects related to chronic allergic pulmonary inflammation in mice.

Nesta investigação realizamos um estudo de caso no âmbito da formação do Engenheiro Agrônomo no curso de Agronomia da Universidade Federal do Rio Grande do Sul (UFRGS). A primazia foi pelo diagnóstico da reformulação curricular iniciada em 2006 e implantada em 2009 frente às adequações do curso às Diretrizes Curriculares Nacionais. Sendo assim, realizamos um estudo, buscando detectar quais foram as contribuições na dinâmica curricular, metodológica, institucional e organizacional e, se estas criaram subsídios eficazes e inovadores para o desenvolvimento do curso. Para atingirmos nossos objetivos realizamos análise documental e de conteúdo nas Diretrizes Curriculares Nacionais para o Curso de Agronomia, nas Atas da Comissão de Reestruturação do Currículo, nas Atas de reuniões da Comissão de Graduação e no Projeto Pedagógico do Curso. Também, sistematicamente triangulamos dados oriundos das avaliações institucionais dos docentes e disciplinas, reuniões de planejamento, questionários, entrevistas, fóruns de debate para docentes e discentes via plataforma Moodle, disponibilizados no Portal da UFRGS. Os resultados apontam que o processo de reformulação curricular propiciou algumas mudanças significativas nos princípios educativos e nos elementos estruturais, componentes essenciais para a construção de um novo modelo pedagógico de formação para o Engenheiro Agrônomo e, também inovou quanto à estrutura da matriz curricular que compõe o conhecimento profissional. Diante dos dados levantados, entendemos que as configurações curriculares analisadas contemplam e condizem plenamente para uma formação de profissionais integrando formação técnica à social. Os argumentos para a defesa da tese foram construídos com as contribuições de vários autores tais como Apple (1989); Bardin (2006); Flick (2009); Lopes (1999, 2004); Lüdke (1986); Minayo (2007, 2011); Moreira (1994,1997; ); Nora (1993); Richardson (1989); Sacristán (2000); Santomé (1998); Silva (1993, 2005); Stenhouse (1987); Triviños (2009); Yin (2005), entre outros. / This research is a case study on the Graduating Course in Agronomy Engineering of the Brazilian Federal University in the state of Rio Grande do Sul (Universidade Federal do Rio Grande do Sul - UFRGS). The emphasis was on diagnosing the curricular remodeling, which began in 2006 and was implemented in 2009, such remodeling came to suit the adjustments of the national curricular guidelines. Thus, we conducted a study aiming to detect which were the contributions on organizational, institutional, methodological and curricular dynamics and if those contributions made up to effective and innovating subsidies to the course development. In order to achieve our aims, we went through documental analysis on the national curricular guidelines to the Agronomy Course. That was done also on the curricular remodeling protocols, the graduation commission meeting protocols and the course’s pedagogical project. Further, we systematically crossed the date originated from professors and courses’ evaluations, planning meetings, questionnaires, interviews, professors and students debate forums on Moodle, all of which available on UFRGS’s web portal. The results point to that the curricular remodeling process provided some meaningful changes in the educational principles and the structural elements, such components are essential to the building of a new graduating pedagogical model of the Agronomist Engineer. It also innovated the curriculum structure which draws up the professional knowledge. Giving the data collected, we understand that the analyzed curricular settings fully contemplate and favor the formation of professionals, integrating technical and social education. The theoretical bases for this thesis were upon the contribution of various authors, e.g. Apple (1989); Bardin (2006); Flick (2009); Lopes (1999, 2004); Lüdke (1986); Minayo (2007, 2011); Moreira (1994, 1997); Nora (1993); Richardson (1989); Sacristán (2000); Santomé (1998); Silva (1993, 2005); Stenhouse (1987); Triviños (2009); Yin (2005).

Chan Ka Wai, Jennifer. / "Architecture Department, Chinese University of Hong Kong, Master of Architecture Programme 2009-2010, design report." / "May 2010."

O infarto agudo do miocárdio (IAM) é a principal causa de mortalidade mundial. O IAM é acompanhado de remodelamento cardíaco, caracterizado por alterações gênicas, moleculares e celulares, com consequentes alterações no tamanho, forma e função do coração, e resultante disfunção ventricular e insuficiência cardíaca. Evidências experimentais e clínicas indicam que a prevenção ou o tratamento do remodelamento cardíaco beneficiam a função ventricular. A LDE é uma nanopartícula lipídica, com estrutura semelhante à lipoproteína de baixa densidade (LDL). A LDE tem a capacidade de se concentrar em células com superexpressão de receptores de LDL, como em processos proliferativos e inflamatórios, sendo utilizada com um direcionador de fármacos a sítios específicos. Nosso laboratório demonstrou que o tratamento com metotrexato (MTX), um fármaco antiproliferativo e imunossupressor, associado à LDE reduziu acentuadamente as lesões ateroscleróticas na aorta de coelhos submetidos à dieta hipercolesterolêmica. Esses resultados nos levaram à hipótese de que a LDE-MTX possa ser utilizada para minimizar o processo inflamatório pós-IAM, determinante para o remodelamento cardíaco, e seus efeitos deletérios. O objetivo do trabalho foi investigar o efeito do tratamento da LDE-MTX sobre o remodelamento cardíaco em ratos submetidos ao IAM. Ratos machos Wistar (300-400g) foram submetidos ao modelo cirúrgico de IAM ou à cirurgia fictícia (SHAM). Os grupos foram divididos entre: SHAM (solução fisiológica), IAM-LDE, IAMMTXc (metotrexato comercial), IAM-LDE-MTX. Os animais foram tratados uma vez por semana na dose de 1 mg/kg intraperitonealmente, por 6 semanas. Após 24 horas do IAM e ao final do seguimento, foi realizado o ecocardiograma. O coração, o pulmão, o fígado e os rins foram coletados para obtenção do peso relativo dos órgãos. O tamanho do IAM foi estimado pela média dos tamanhos dos IAM externo e interno. A avaliação da necrose dos miócitos, processo inflamatório, diâmetro dos miócitos e fibrose miocárdica nas regiões subendocárdica (SE) e intersticial (INT) foi realizada na região remota ao IAM. Marcadores de estresse oxidativo, inflamação, fibrose, angiogênese e os receptores de lipoproteínas foram quantificados por PCR em tempo real. O tratamento com LDE-MTX diminuiu a dilatação do VE, hipertrofia cardíaca, volumes sistólicos e diastólicos, espessura do septo interventricular e da parede posterior e massa do VE, comparado aos grupos IAM-LDE e IAM-MTXc. Além disso, houve uma melhora de aproximadamente 40% da função sistólica do VE em relação aos demais grupos IAM. O tratamento com LDE-MTX não alterou a função diastólica. O peso relativo do coração e do pulmão foi menor no grupo IAM-LDE-MTX quando comparado ao IAM-LDE. Na histomorfometria, houve diminuição no tamanho do infarto no grupo IAM-LDE-MTX quando comparado com IAMLDE. A necrose, infiltrado inflamatório e fração de volume do colágeno nas regiões INT e SE foram menores no IAM-LDE-MTX em relação aos grupos IAM-LDE e IAM-MTXc, assim como o diâmetro dos miócitos. A expressão gênica dos marcadores de estresse oxidativo e fibrose foi menor no grupo IAM-LDE-MTX quando comparado ao grupo IAM-MTXc. Com relação à inflamação, o grupo IAM-LDE-MTX apresentou menor expressão do gene para TNF-alfa quando comparado aos grupos IAM-MTXc e SHAM. No que se refere ao receptor de lipoproteína, nos grupos IAM-LDE-MTX houve menor expressão do gene para receptor de lipoproteína de baixa densidade (LDLR) quando comparado ao grupo tratado com MTXc. Não foi observada toxicidade em nenhum grupo. Os resultados deste estudo indicam que o tratamento com LDE-MTX melhora significantemente a função cardíaca e atenua o remodelamento cardíaco em modelo experimental cirúrgico para IAM / Acute myocardial infarction (AMI) is the main cause of worldwide mortality. AMI is accompanied by cardiac remodeling, characterized by genetic, molecular and cellular alterations, with consequent changes in the size, shape and function of the heart, resulting in ventricular dysfunction and heart failure. Experimental and clinical evidence indicate that prevention or treatment of cardiac remodeling benefits the ventricular function. LDE is a lipid nanoparticle with a structure similar to low density lipoprotein (LDL). LDE has the ability to concentrate in cells with overexpression of LDL receptors, such as in proliferative and inflammatory processes, and is used with a drugtargeting agent at specific sites. Our laboratory demonstrated that the treatment with methotrexate (MTX), an antiproliferative and immunosuppressive drug, associated to LDE markedly reduced atherosclerotic lesions in aorta of rabbits submitted to the hypercholesterolemic diet. These results led us to the hypothesis that LDEMTX could be used to minimize the post-AMI inflammatory process, determinant for cardiac remodeling, and their deleterious effects. The aim of this study was to investigate the effect of LDE-MTX treatment on cardiac remodeling in rats submitted to AMI. Male Wistar rats (300-400g) were submitted to the surgical model of AMI or Sham surgery. The groups were divided into: SHAM (saline solution), AMI-LDE, AMI-MTXc (commercial methotrexate), AMI-LDE-MTX. The animals were treated once a week at a dose of 1 mg/kg intraperitoneally, for 6 weeks. After 24 hours of AMI and at the end of the follow-up, the echocardiogram was performed. The heart, lung, liver and kidneys were collected to obtain the relative weight of the organs. Infaction size was estimated by mean extern and intern size of IAM. Evaluation of myocyte necrosis, inflammatory process, myocyte diameter and myocardial fibrosis in the subendocardial (SE) and interstitial (INT) areas was performed in remote area from AMI. Markers of oxidative stress, inflammation, fibrosis, angiogenesis and lipoprotein receptors were quantified by quantitative real-time PCR. Treatment with LDE-MTX decreased LV dilation, cardiac hypertrophy, systolic and diastolic volumes, interventricular septum and posterior wall thickness and LV mass, compared to AMI-LDE and AMI-MTXc groups. In addition, there was an improvement of approximately 40% of LV systolic function compared to other AMI groups. Treatment with LDE-MTX did not alter diastolic function. The relative weight of the heart and lung were lower in the AMI-LDE-MTX group when compared to the AMI-LDE. In morphometry, infarct size decreased in the AMI-LDE-MTX group when compared to AMI-LDE. Necrosis, inflammatory infiltrate and collagen volume fraction in the INT and SE regions were lower in AMI-LDEMTX than in AMI-LDE and AMI-MTXc groups, as well as the myocyte diameter. The gene expression of oxidative stress and fibrosis markers were lower in the AMI-LDE-MTX group when compared to the AMI-MTXc. Regarding inflammation, the AMI-LDE-MTX group had lower expression of the TNF-alfa gene when compared to the AMI-MTXc group and the SHAM group. As regards the lipoprotein receptor, in the AMI-LDE-MTX there was lower expression of the gene for low-density lipoprotein (LDLR) receptor compared to MTXc treated animals. No toxicity was observed in any groups. The results of this study indicate that treatment with LDE-MTX significantly improves cardiac function and attenuates cardiac remodeling in an experimental surgical model for AMI