Transit preferential treatment : a public policy-making perspective

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Civil and Environmental Engineering, 2003.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Includes bibliographical references.Buses and in general at-grade public transportation remain the most important component of transit services in all the urban areas, whether they are feeder to a heavy rail system or an independent network. However, the steady increase in travel demand, essentially private automobile, has results in a growing level of congestion, affecting both cars and public transportation. In response, cities like Curitiba and Zurich moved in the late 70's towards the implementation of preferential treatment. To do that, they introduced innovative policies in order to give the full priority to transit. Preferential treatment is a broad definition that combines all the means to insure that priority is given to transit (queue jump, traffic signal priority, exclusive lane, tramways ...). The main concerns about Zurich and Curitiba are that they both achieved their implementation through particular policymaking processes; moreover the generalization of these types of policies has been very limited. The objectives of this thesis are to apply the three models from the agenda-building theory (Mobilization, Inside Access and Outside Initiative) to the context of public transportation to understand how innovative policy-making can be introduced and if the presence of a policy entrepreneur is necessary and sufficient. Using 11 cities in Europe and America that have implemented preferential treatment as case studies, the thesis identified elements necessary to address the public reaction, the institutional fragmentation and the decision-makers' positions. The research shows the necessity of public consultations and comprehensive planning exercises to convince the different stakeholders. Moreover, it points out the benefits of initiatives such as benchmarking or national legislation. Eventually, the thesis concludes that the policy-making theory can be expanded in acknowledging a combination of models to describe the preferential treatment's implementation process. On the other hand, the context of public transportation has evolved enough (concentration of decision powers and increasing public support) so that transit agencies can move towards implementation in focusing on stakeholder management strategies instead of relying on a policy entrepreneur.by Michael Pulichino.S.M

Genetic regulation of pituitary gland development in human and mouse

Normal hypothalamopituitary development is closely related to that of the forebrain and is dependent upon a complex genetic cascade of transcription factors and signaling molecules that may be either intrinsic or extrinsic to the developing Rathke’s pouch. These factors dictate organ commitment, cell differentiation, and cell proliferation within the anterior pituitary. Abnormalities in these processes are associated with congenital hypopituitarism, a spectrum of disorders that includes syndromic disorders such as septo-optic dysplasia, combined pituitary hormone deficiencies, and isolated hormone deficiencies, of which the commonest is GH deficiency. The highly variable clinical phenotypes can now in part be explained due to research performed over the last 20 yr, based mainly on naturally occurring and transgenic animal models. Mutations in genes encoding both signaling molecules and transcription factors have been implicated in the etiology of hypopituitarism, with or without other syndromic features, in mice and humans. To date, mutations in known genes account for a small proportion of cases of hypopituitarism in humans. However, these mutations have led to a greater understanding of the genetic interactions that lead to normal pituitary development. This review attempts to describe the complexity of pituitary development in the rodent, with particular emphasis on those factors that, when mutated, are associated with hypopituitarism in humans

Applying refinement to the use of mice and rats in rheumatoid arthritis research

Rheumatoid arthritis (RA) is a painful, chronic disorder and there is currently an unmet need for effective therapies that will benefit a wide range of patients. The research and development process for therapies and treatments currently involves in vivo studies, which have the potential to cause discomfort, pain or distress. This Working Group report focuses on identifying causes of suffering within commonly used mouse and rat ‘models’ of RA, describing practical refinements to help reduce suffering and improve welfare without compromising the scientific objectives. The report also discusses other, relevant topics including identifying and minimising sources of variation within in vivo RA studies, the potential to provide pain relief including analgesia, welfare assessment, humane endpoints, reporting standards and the potential to replace animals in RA research

Silencing CD36 gene expression results in the inhibition of latent-TGF-β1 activation and suppression of silica-induced lung fibrosis in the rat

<p>Abstract</p> <p>Background</p> <p>The biologically active form of transforming growth factor-β1 (TGF-β1) plays a key role in the development of lung fibrosis. CD36 is involved in the transformation of latent TGF-β1 (L-TGF-β1) to active TGF-β1. To clarify the role of CD36 in the development of silica-induced lung fibrosis, a rat silicosis model was used to observe both the inhibition of L-TGF-β1 activation and the antifibrotic effect obtained by lentiviral vector silencing of CD36 expression.</p> <p>Methods</p> <p>The rat silicosis model was induced by intratracheal injection of 10 mg silica per rat and CD36 expression was silenced by administration of a lentiviral vector (Lv-shCD36). The inhibition of L-TGF-β1 activation was examined using a CCL-64 mink lung epithelial growth inhibition assay, while determination of hydroxyproline content along with pathological and immunohistochemical examinations were used for observation of the inhibition of silica-induced lung fibrosis.</p> <p>Results</p> <p>The lentiviral vector (Lv-shCD36) silenced expression of CD36 in alveolar macrophages (AMs) obtained from bronchoalveolar lavage fluid (BALF) and the activation of L-TGF-β1 in the BALF was inhibited by Lv-shCD36. The hydroxyproline content of silica+Lv-shCD36 treated groups was significantly lower than in other experimental groups. The degree of fibrosis in the silica+Lv-shCD36-treated groups was less than observed in other experimental groups. The expression of collagen I and III in the silica+Lv-shCD36-treated group was significantly lower than in the other experimental groups.</p> <p>Conclusion</p> <p>These results indicate that silencing expression of CD36 can result in the inhibition of L-TGF-β1 activation in a rat silicosis model, thus further preventing the development of silica-induced lung fibrosis.</p

Early onset obesity and adrenal insufficiency associated with a homozygous POMC mutation

Isolated hypocortisolism due to ACTH deficiency is a rare condition that can be caused by homozygous or compound heterozygous mutations in the gene encoding proopiomelanocortin (POMC). Loss of function mutations of POMC gene typically results in adrenal insufficiency, obesity and red hair. We describe an 18 month old Hispanic female with congenital adrenal insufficiency, a novel POMC mutation and atypical clinical features. The patient presented at the age of 9 months with hypoglycemia and the endocrine evaluation resulted in a diagnosis of ACTH deficiency. She developed extreme weight gain prompting sequence analysis of POMC, which revealed a homozygous c.231C > A change which is predicted to result in a premature termination codon. The case we report had obesity, hypocortisolism but lacked red hair which is typical for subjects with POMC mutations. Mutations of POMC should be considered in individuals with severe early onset obesity and adrenal insufficiency even when they lack the typical pigmentary phenotype

Asistencia técnica y capacitación en hábitat precario : Asentamientos informales. Villa Elvira. La Plata

El proyecto de extensión prevé en uno de sus 4 ejes el diseño, programación y realización de talleres participativos de capacitación en construcción, teóricos-prácticos. De los mismos se espera dejar instalada la capacidad de la identificación, de la búsqueda de la mejor resolución al problema y de resolverlo con acciones coordinadas integrales, hacia mejores condiciones habitacionales y de calidad de vida. Este tipo de asistencia técnica y organizacional sumada al saber popular de la población de escasos recursos de la periferia de La Plata, genera un potencial que revaloriza los saberes -técnicos y populares-, construyendo colectivamente capacidades que apuntan a resolver problemas constructivos reales en un hábitat precario, donde emergen la transformación, el mejoramiento, el aprendizaje, la integración, el respeto, la comunicación, el servicio, entre otros. Tanto San Carlos como la zona periférica de Villa Elvira, son barrios con escasos recursos y una innumerable cantidad de necesidades básicas insatisfechas. Familias asentadas en terrenos informales, inundables, no aptos para el desarrollo saludable de la vida. Es por esto y más, que el equipo identifica como prioritario desarrollar talleres que apunten a mejorar y/o aportar a las mejoras del hábitat popular.Área temática 2: Tecnología - Eje ExtensiónFacultad de Arquitectura y Urbanism

Asistencia técnica y capacitación en hábitat precario : Asentamientos informales. Villa Elvira. La Plata

El proyecto de extensión prevé en uno de sus 4 ejes el diseño, programación y realización de talleres participativos de capacitación en construcción, teóricos-prácticos. De los mismos se espera dejar instalada la capacidad de la identificación, de la búsqueda de la mejor resolución al problema y de resolverlo con acciones coordinadas integrales, hacia mejores condiciones habitacionales y de calidad de vida. Este tipo de asistencia técnica y organizacional sumada al saber popular de la población de escasos recursos de la periferia de La Plata, genera un potencial que revaloriza los saberes -técnicos y populares-, construyendo colectivamente capacidades que apuntan a resolver problemas constructivos reales en un hábitat precario, donde emergen la transformación, el mejoramiento, el aprendizaje, la integración, el respeto, la comunicación, el servicio, entre otros. Tanto San Carlos como la zona periférica de Villa Elvira, son barrios con escasos recursos y una innumerable cantidad de necesidades básicas insatisfechas. Familias asentadas en terrenos informales, inundables, no aptos para el desarrollo saludable de la vida. Es por esto y más, que el equipo identifica como prioritario desarrollar talleres que apunten a mejorar y/o aportar a las mejoras del hábitat popular.Área temática 2: Tecnología - Eje ExtensiónFacultad de Arquitectura y Urbanism

Inhibition of TGF-β Signaling and Decreased Apoptosis in IUGR-Associated Lung Disease in Rats

Intrauterine growth restriction is associated with impaired lung function in adulthood. It is unknown whether such impairment of lung function is linked to the transforming growth factor (TGF)-β system in the lung. Therefore, we investigated the effects of IUGR on lung function, expression of extracellular matrix (ECM) components and TGF-β signaling in rats. IUGR was induced in rats by isocaloric protein restriction during gestation. Lung function was assessed with direct plethysmography at postnatal day (P) 70. Pulmonary activity of the TGF-β system was determined at P1 and P70. TGF-β signaling was blocked in vitro using adenovirus-delivered Smad7. At P70, respiratory airway compliance was significantly impaired after IUGR. These changes were accompanied by decreased expression of TGF-β1 at P1 and P70 and a consistently dampened phosphorylation of Smad2 and Smad3. Furthermore, the mRNA expression levels of inhibitors of TGF-β signaling (Smad7 and Smurf2) were reduced, and the expression of TGF-β-regulated ECM components (e.g. collagen I) was decreased in the lungs of IUGR animals at P1; whereas elastin and tenascin N expression was significantly upregulated. In vitro inhibition of TGF-β signaling in NIH/3T3, MLE 12 and endothelial cells by adenovirus-delivered Smad7 demonstrated a direct effect on the expression of ECM components. Taken together, these data demonstrate a significant impact of IUGR on lung development and function and suggest that attenuated TGF-β signaling may contribute to the pathological processes of IUGR-associated lung disease

Stem Cells, Self-Renewal, and Lineage Commitment in the Endocrine System

The endocrine system coordinates a wide array of body functions mainly through secretion of hormones and their actions on target tissues. Over the last decades, a collective effort between developmental biologists, geneticists, and stem cell biologists has generated a wealth of knowledge related to the contribution of stem/progenitor cells to both organogenesis and self-renewal of endocrine organs. This review provides an up-to-date and comprehensive overview of the role of tissue stem cells in the development and self-renewal of endocrine organs. Pathways governing crucial steps in both development and stemness maintenance, and that are known to be frequently altered in a wide array of endocrine disorders, including cancer, are also described. Crucially, this plethora of information is being channeled into the development of potential new cell-based treatment modalities for endocrine-related illnesses, some of which have made it through clinical trials