Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2016-09-16T15:30:46Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) NOVAS EVIDÊNCIAS DA DISTRIBUIÇÃO ESPACIAL DAS INDÚSTRIAS NO .pdf: 1468981 bytes, checksum: def3edbec1ba14e726b735dbe57ee3b3 (MD5) / Made available in DSpace on 2016-09-16T15:30:46Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) NOVAS EVIDÊNCIAS DA DISTRIBUIÇÃO ESPACIAL DAS INDÚSTRIAS NO .pdf: 1468981 bytes, checksum: def3edbec1ba14e726b735dbe57ee3b3 (MD5) Previous issue date: 2016-02-29 / CAPES / A recente dinâmica de crescimento econômico, observado na década de 2000, ocasionou profundas mudanças na estrutura econômica, e consequentemente na composição do emprego e na distribuição das empresas na região Nordeste, pertencentes à indústria de transformação. Desta forma, este estudo se propôs a realizar uma análise do padrão de distribuição locacional da indústria de transformação no Nordeste mediante a utilização da metodologia desenvolvida por Ellison e Glaeser (1994), para o período correspondente aos anos de 2005 e 2010, observando-se a evolução e as peculiaridades deste processo nesta região. A base de dados utilizada foram os microdados do Relatório Anual de Informações Sociais (RAIS) do Ministério do Trabalho e Emprego (MTE), ao nível da firma. Os resultados observados no estudo consistem em uma significativa desconcentração média da indústria de transformação durante o período, verificando-se também que este resultado foi condicionado à migração ou instalação de novas plantas industriais de maior porte para localidades que apresentaram um desenvolvimento recente na região. Apesar disso, foi observado que quatro dos nove estados da federação pertencentes à região exibiram resultados para o índice que indicam a continuidade da concentração industrial nos mesmos. Por fim, verificou-se duas tendências distintas quando a análise do referido índice é realizada por nível de intensidade tecnológica dos setores da indústria de transformação, ou seja, os setores classificados como de baixa e média intensidade tecnológica tenderam a se desconcentrar no período, enquanto aqueles classificados como de média-alta e alta intensidade tecnológica permaneceram mais concentrados. / The recent momentum of economic growth, noted in late 2000, brought about profound changes in the economic structure, and consequently in the composition of employment and distribution companies in the northeastern region, belonging to the processing industry. Thus, this study proposed to conduct an examination of the locational distribution pattern of the manufacturing industry in the Northeast using the methodology developed by Ellison and Glaeser (1994), for the period corresponding to the years 2005 and 2010, observing the evolution and the peculiarities of this process in this region. The database used was the micro-data of the Annual Report of Social Information (RAIS) of the Ministry of Labor and Employment (MTE), at the level of the firm. The results observed in the study consist of a significant devolution of average manufacturing industry during the period, noting that this result was conditioned to migration or installation of new larger industrial plants for locales that presented a recent development in the region. Nevertheless, it was observed that four of the nine States of the Federation belonging to the region exhibited results to the index that indicates the continuity of industrial concentration. Finally, there has been two distinct trends when the analysis of that index is held by technological intensity level of the sectors of the processing industry, i.e. the sectors classed as medium and low technological intensity tended to Psych in the period, while those classified as of medium-high and high technological intensity remained focused.

Made available in DSpace on 2014-10-09T12:51:33Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T13:56:30Z (GMT). No. of bitstreams: 0 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Dissertacao (Mestrado) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP / FAPESP:04/04148-3

Made available in DSpace on 2014-10-09T12:35:47Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:03:51Z (GMT). No. of bitstreams: 0 / Os íons terras raras apresentam propriedades espectroscópicas diferenciadas e números de coordenação entre 6 e 12 e seu estado de oxidação mais comum é o íon trivalente. Apesar de esses íons apresentarem uma baixa intensidade de luminescência, em função de sua baixa absortividade molar, esses são capazes de formar complexo onde o ligante absorva luz e transfira para o centro metálico essa energia, fenômeno conhecido como efeito antena. Essas propriedades tornam os seus complexos alvos de estudos como marcadores em ensaios imunoluminescentes, aliado ao uso de nanopartículas poliméricas. Todos esses fatores podem ser utilizados para a montagem de uma metodologia para o diagnóstico da doença de Chagas, doença tropical negligenciada, que apesar de seus mais de 100 anos após descoberta, ainda possui diversas questões em aberto e sem estudo aprofundado. Dessa maneira, propomo-nos a sintetizar e caracterizar nanopartículas de PHB misturadas aos complexos de terras raras, especificamente, complexos -dicetona - Tb3+ , Sm3+ , Gd3+, ou Eu3+. Pretende-se ligar essas nanopartículas a um espaçador como o glutaraldeído ou então diretamente a um anti-IgG humano e assim, num acoplamento antigeno-anticopo verificar sua emissão de luminescência para detecção de soro positivo para a doença. Dessa forma, obtém-se um biomarcador luminescente para diagnóstico da doença de Chagas. / Dissertação (Mestrado) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

Orientador: Lucia Elvira Alvares / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-13T02:44:23Z (GMT). No. of bitstreams: 1 Grade_CarlaVermeulenCarvalho_M.pdf: 54304678 bytes, checksum: 869f67d6a836e256bbd7ee9e15980659 (MD5) Previous issue date: 2009 / Resumo: A proteina Miostatina (tambem conhecida como GDF8) e um membro da superfamilia de crescimento e diferenciacao ß (TGF- ß) e e expressa quase que exclusivamente em musculatura esqueletica, tanto no embriao em desenvolvimento quanto no individuo adulto, onde circula livre pela corrente sanguinea. A Miostatina foi inicialmente identificada em 1997 por MCPHERRON et al. e, desde entao, muitos estudos tem demonstrado seu papel essencial na regulacao do desenvolvimento de musculatura esqueletica de aves e mamiferos. O nocaute genico da Miostatina causa hiperplasia e hipertrofia das fibras musculares, resultando em musculos individuais ate duas vezes maiores do que em animais selvagens. Isso demonstra que a Miostatina e um regulador negativo da deposicao de musculatura esqueletica. A estrutura e a funcao desta proteina sao conservadas em diversas especies, incluindo humanos, onde os niveis de Miostatina circulante no sangue se encontram aumentados durante condicoes de distrofia e na caquexia que acompanha alguns tipos de cancer e a AIDS. Um melhor entendimento dos mecanismos que regem a expressao da Miostatina e essencial para o desenvolvimento de estrategias que possam regular sua atividade durante tais condicoes. No presente trabalho, nos identificamos, com o uso de ferramentas de Bioinformatica, elementos cisregulatorios putativos (promotor e enhancers) que possivelmente regulam a transcricao do gene da Miostatina. Inicialmente foi realizada uma comparacao dos loci do GDF8, incluindo as regioes intergenicas adjacentes, provenientes dos genomas de Humano, Camundongo e Galinha. Essa analise revelou a presenca de diferentes regioes evolutivamente conservadas (RECs) adjacentes a sequencia codificadora desta proteina, sete downstream e uma upstream ao gene. Por terem sido mantidas relativamente conservadas ao longo da evolucao, essas regioes supostamente possuem um papel funcional, possivelmente como elementos cis-regulatorios do gene da Miostatina. Em seguida, com o intuito de entender as funcoes que cada uma dessas regioes possa estar exercendo sobre a regulacao da atividade transcricional do gene da Miostatina, foi realizada uma busca por sitios de ligacao para fatores transcricionais que tenham sido conservados evolutivamente nessas RECs. Muitos sitios conservados foram observados nas sete RECs downstream ao gene da Miostatina, entre eles estao sitios para fatores relacionados ao desenvolvimento de musculatura esqueletica (MyoD, Myogenin, E47, EN1), membros (Pax3, Tbx5) e coracao (Nkx2.5, Pitx2). Juntos, esses dados sugerem uma regulacao modular do gene da Miostatina durante a embriogenese dos vertebrados. A unica REC localizada upstream ao GDF8 representa o promotor minimo putativo deste gene. Essa hipotese e reforcada pela presenca de um sitio de ligacao conservado para a Proteina de Ligacao ao sitio TATA. Com o intuito de validar as hipoteses formuladas com base nas analises de Bioinformatica, no presente trabalho buscamos caracterizar funcionalmente o promotor minimo do gene da Miostatina. Para tanto, a regiao do promotor minimo foi inicialmente clonada em um vetor que nao contem promotor e possui como gene reporter o GFP. Essa construcao de expressao foi entao testada atraves de experimentos de eletroporacao em embrioes de galinha in ovo. A analise dos embrioes eletroporados revelou que a regiao de DNA elegida para as analises funcionais e capaz de dirigir a transcricao do gene reporter, indicando que ela corresponde ao promotor minimo do gene da Miostatina. Alem do sitio TATA, ha, na regiao do promotor, diversos sitios conservados para a ligacao de proteinas envolvidas na via de sinalizacao mediada por cAMP (CREB, ATF, NFY). Esse achado esta de acordo com estudos recentes que demonstram o envolvimento do cAMP na regulacao dos fatores miogenicos Myf5 e MyoD, bem como de Pax3, sugerindo que a atividade do gene da Miostatina tambem possa estar sendo regulada por essa via de sinalizacao. Outras regioes do genoma humano que possuem arquitetura semelhante a observada no promotor da Miostatina foram identificadas, demonstrando que outros genes podem estar sob influencia da mesma via de sinalizacao que regula a atividade do promotor da Miostatina, dentre eles genes envolvidos na miogenese e neurogenese. / Abstract: The Myostatin protein (also known as GDF8) is a member of the transforming growth factor-ß (TGF-ß) superfamily and is expressed almost exclusively in skeletal muscle, both in the embryo and in the adult, where the protein circulates in the blood flow. It was initially identified in 1997 by MCPHERRON et al., and since then many studies have been demonstrating its essential role in the regulation of the development of skeletal muscle from birds and mammals. The knockout of the Myostatin gene causes both hyperplasia and hypertrophy of the skeletal muscle fibers, resulting in muscles twice as big as the wildtype ones, thus showing that Myostatin is a negative regulator of skeletal muscle deposition. The GDF8 structure and function is conserved in many species, including humans where the Myostatin levels are increased during dystrophy conditions and in the cachexia that accompanies some types of cancer and AIDS. A better understanding of the mechanisms that rule the Myostatin expression is essential for the development of strategies that might regulate its activity during such conditions. In this research, we have identified, with the use of bioinformatic tools, the cis-regulatory elements (promoter and enhancers) that regulate the Myostatin gene transcription. We compared the GDF8 loci from human, chicken and mouse and found different evolutionary conserved regions (ECRs), adjacent to the GDF8 coding sequence. Because these intergenic sequences remained relatively conserved throughout evolution, they supposedly have a functional role, possibly as cis-regulatory elements for the Myostatin gene. Our analyses revealed the presence of seven possible enhancers downstream of the GDF8 gene and one conserved region upstream of it. In order to understand the role these regions might have in the regulation of Myostatin's transcription activity, we searched for binding sites that were also evolutionary conserved. Many conserved binding sites were observed in the RECs downstream to the Myostatin gene, and among them are sites for factors related to the development of the skeletal muscle (MyoD, Myogenin, E47, EN1), limbs (Pax3, Tbx5) and heart (Nkx2.5, AREB6, Pitx2). Together, these data suggest a modular regulation of the Myostatin gene during vertebrates' embryogenesis. The only REC observed upstream of the Myostatin locus represents the putative basal gene promoter. This hypothesis is strengthened by the presence of a binding site for the Tata Binding Protein conserved for the studied species. In this research, we aimed at functionally characterizing the Myostatin gene basal promoter. For that purpose, we cloned the studied region in a promoterless vector, which contains GFP as a reporter gene. This expression construct was then tested through in ovo electroporation assays. The analysis of the electroporated embryos revealed that the cloned DNA region is capable of driving the transcription of the reporter gene, which indicates that it truly corresponds to the basal promoter of the Myostatin gene. Moreover, there are conserved binding sites for the CREB and ATF1 transcription factors in the basal promoter, which are activated by the cAMP signaling path. This finding is in agreement with recent studies that demonstrate the involvement of cAMP in the regulation of the myogenic factors Myf5 and MyoD, as well as Pax3, thus suggesting that the activity of the Myostatin gene might be under the influence of this signaling path. Other regions of the human genome that have a similar architecture to the one observed in the Myostatin promoter were identified. This demonstrates that other genes are possibly under the influence of the same signaling path regulating the activity of the Myostatin promoter, among them genes involved in myogenesis and neurogenesis. / Mestrado / Histologia / Mestre em Biologia Celular e Estrutural

Orientador: Lucia Elvira Alvares / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-22T18:28:57Z (GMT). No. of bitstreams: 1 Grade_CarlaVermeulenCarvalho_D.pdf: 3007033 bytes, checksum: 522d9d385305f8744861d38f7dabf5aa (MD5) Previous issue date: 2013 / Resumo: A Miostatina é um regulador negativo da deposição de musculatura esquelética e mutações no gene que codifica esta proteína têm sido associadas a um aumento marcante na massa muscular de organismos vertebrados, resultado de hiperplasia e hipertrofia das fibras musculares. Nosso grupo identificou previamente o promotor basal do gene da Miostatina e análises de bioinformática revelaram a presença de sítios evolutivamente conservados para a ligação de CREB, Meis, FXR e NFY, além de um sítio TATA. No presente trabalho nós utilizamos mutagênese sítio-dirigida para gerar diversas construções delecionais que possuem um ou mais sítios mutados, e testamos sua atividade in vitro usando mioblastos C2C12 de camundongo sob condições de proliferação e diferenciação, para analisar o papel destes sítios de ligação sobre a atividade do promotor. Os resultados mostraram que FXR aparentemente não confere efeito na atividade transcricional do promotor da Miostatina em ambos os momentos analisados, indicando que o papel regulador desta proteína pode estar relacionado ao controle da expressão da Miostatina em outro tipo celular, que não o mioblasto. O NFY apresentou um papel de ativador transcricional, enquanto CREB e Meis atuaram inicialmente como repressores durante a proliferação, passando a relaxar esta repressão durante a diferenciação dos mioblastos, permitindo que a atividade do promotor aumentasse significativamente. Trabalhando juntos, estes fatores de transcrição são capazes de manter a atividade do promotor em níveis mais baixos durante a proliferação dos mioblastos e, com o início da diferenciação, a repressão é liberada, e os níveis de atividade podem aumentar. Este padrão está de acordo com o padrão de expressão dinâmico observado para a proteína da Miostatina durante o desenvolvimento da musculatura esquelética em vertebrados / Abstract: Myostatin is a negative regulator of skeletal muscle deposition and mutations in the gene that encodes this protein have been associated to a remarkable increase in skeletal muscle mass, attributable to both hyperplasia and hypertrophy. We have previously identified Myostatin's basal promoter and bioinformatic analyses revealed the presence of evolutionarily conserved binding sites for CREB, Meis, FXR and NFY, besides a TATA box. In the present study we used site-directed mutagenesis to generate several expression constructs possessing one or more mutated sites, and tested their activity in vitro using mouse C2C12 myoblasts in proliferation and differentiation conditions, to analyze the role of these sites on the activity of the promoter. The results show that FXR appears not to confer any effect on the transcriptional activity of the promoter in both conditions, indicating that the regulatory role of this protein might be involved in the control of Myostatin expression in another cell type. NFY presents a role as transcriptional activator, while CREB and Meis act initially as repressors during proliferation, releasing this repression upon differentiation, which allows the activity of the promoter to significantly increase. Working together, these transcription factors are capable of maintaining the promoter activity at lower levels during the proliferation of myoblasts and, upon differentiation, the repression is released, and activity levels can be increased. This pattern is in agreement with the dynamic expression pattern observed for Myostatin during the skeletal muscle development in vertebrates / Doutorado / Histologia / Doutor em Biologia Celular e Estrutural

A novel approach is proposed for modeling of structurally variable regions in proteins. In this approach, a prerequisite sequence-structure alignment is examined for regions where the target sequence is not covered by the structural template. These regions, extended with a number of residues from adjacent stem regions, are submitted to fold recognition. The alignments produced by fold recognition are integrated into the initial alignment to create a multiple alignment where gaps in the main structural template are covered by local structural templates. This multiple alignment is used to create a protein model by existing protein modeling techniques. Several alternative parameters are evaluated using a set of ten proteins. One set of parameters is selected and evaluated using another set of 31 proteins. The most promising result is for loop regions not located at the C- or N-terminal of a protein, where the method produces an average RMSD 12% lower than the loop modeling provided with the program MODELLER. This improvement is shown to be statistically significant.

In this paper we put forward a Bayesian Model Averaging method aimed at performing inference under model uncertainty in the presence of potential spatial autocorrelation. The method uses spatial filtering in order to account for uncertainty in spatial linkages. Our procedure is applied to a dataset of income per capita growth and 50 potential determinants for 255 NUTS-2 European regions. We show that ignoring uncertainty in the type of spatial weight matrix can have an important effect on the estimates of the parameters attached to the model covariates. After integrating out the uncertainty implied by the choice of regressors and spatial links, human capital investments and transitional dynamics related to income convergence appear as the most robust determinants of growth at the regional level in Europe. Our results imply that a quantitatively important part of the income convergence process in Europe is influenced by spatially correlated growth spillovers.

Spatio-temporal reasoning is the area of automated reasoning about space and time and is important in the field of robotics. It is desirable for an autonomous robot to have the ability to reason about both time and space. ST0 is a logic that allows for such reasoning by, among other things, defining a formalism used to describe the relationship between spatial regions and a calculus that allows for deducing further information regarding such spatial relations. An extension of ST0 is ST1 that can be used to describe the relationship between spatial entities across time-points (inter-temporal relations) while ST0 is constrained to doing so within a single time-point. This allows for a better ability of expressing how spatial entities change over time. A major obstacle in using ST1 in practise however, is the fact that any observations made regarding spatial relations between regions is constrained to the time-point in which the observation was made, so we are unable to observe inter-temporal relations. Further complicating things is the fact that deducing such inter-temporal relations is not possible without a frame of reference. This thesis examines one method of overcoming these problems by considering the concept of rigid regions which are assumed to always be unchanging and using them as the frame of reference, or as landmarks. The effectiveness of this method is studied by conducting experiments where a comparison is made between various landmark ratios with respect to the total number of regions under consideration. Results show that when a high degree of intra-temporal relations are fully or partially known, increasing the number of landmark regions will reduce the percentage of inter-temporal relations to be completely unknown. Despite this, very few inter-temporal relations can be fully determined even with a high ratio of landmark regions.

La présente thèse s’inscrit dans le cadre théorique de l’Européanisation qui peut être saisi à travers la notion d’usages instrumentaux, stratégiques, cognitifs et légitimant. L’objet de l’étude est un examen comparatif de l’adaptation des deux régions au nouveau contexte politique, légal et financier qui résulte du développement et de l’extension de l’intégration de l’UE dans le domaine de l’énergie et du changement climatique. Les ‘usages’ réfèrent à la capacité et à la volonté des acteurs de saisir des opportunités et des contraintes européennes pour formuler des politiques nationales (et dans ce cas régionales) traduisant l’impératif de la décarbonisation. Nous avons cherché à mesurer jusqu’à quel point des exécutifs régionaux étaient capables de mobiliser des ressources de l’UE dans le but de poursuivre leurs stratégies dans le domaine de la décarbonisation, ainsi que de déterminer si leur capacité d’utiliser des ressources européennes dépend de leur appartenance à un ‘ancien’ ou à un ‘nouvel’ Etat membre de l’UE. Au final, il s’agit d’évaluer jusqu’à quel point leur capacité d’innover et d’organiser la résilience territoriale à l’aide d’outils européens est liée à la division Est/Ouest. L’analyse est conduite sur deux cas d’études : deux régions européennes qui sont aujourd’hui des émettrices majeures en CO2, parce qu’elles sont encore industrialisées, densément peuplées, qu’elles abritent des sites de production en énergie, et que les bâtiments et les logements (publics et privés) sur leurs territoires sont des passoires énergétiques. La haute Silésie en Pologne et le Nord-Pas de Calais en France peuvent toujours être considérés comme des territoires industrialisés et peuvent être comparés dans une perspective « nouveau/ancien » Etat membre de l’UE. La présente recherche examine les différences dans les usages dans les deux cas d’études. Nous recherchons des variables explicatives pour ces divergences qui peuvent être trouvées dans le passé de chacune des régions. En procédant de cette manière, nous plaçons notre modèle dans une perspective de dépendance au sentier et nous regardons ce qui est pertinent dans le dispositif régional. / The object of the study is a comparative examination of two regions' adaptation to the new political, legal and financial context that results from the development and extension of the EU integration in the field of energy and climate change – or decarbonisation agenda. The ‘usages’ refer to stakeholders’ ability and willingness to take advantage of the European opportunities and constraints provided to them to shape national (and in this case regional) policies. In addition to the intentional dimensions ‘usages’ also cover the actual practices observed in each region. We search to determine to what extent the ability of the regional executives to mobilise EU resources for the purpose of pursuing their strategies in the field of decarbonisation depends on whether they are situated in an ‘old’ or a ‘new’ member state of the EU. We attempt to assess to what extent their ability to innovate and to organise a territorial resilience is related to the East/West divide.The analysis is conduced on two case studies: two European regions that are today major CO2 emitters, because they are still industrialized, densely populated, they host energy production sites, and their housing requires deep and extensive thermal renovation. Two regions in Europe appeared particularly fitting that description, and cumulate all disadvantages (as regards the importance of CO2 emissions). Upper Silesia in Poland and Nord-Pas-de-Calais in France can still be considered as industrialized territories that can be compared in a “new/old” member state of the EU perspective. The present research looks at differences in usages in the two case studies. We search for pertinent explanatory variables for those divergences to be found in each region’s past, deconstructed in institutional, interest-related and ideational components. We place our model in a path-dependence perspective and we look at how it is relevant in a regional setting.

This paper investigates the impact of knowledge capital stocks on total factor productivity through the lens of the knowledge capital model proposed by Griliches (1979), augmented with a spatially discounted cross-region knowledge spillover pool variable. The objective is to shift attention from firms and industries to regions and to estimate the impact of cross-region knowledge spillovers on total factor productivity (TFP) in Europe. The dependent variable is the region-level TFP, measured in terms of the superlative TFP index suggested by Caves, Christensen and Diewert (1982). This index describes how efficiently each region transforms physical capital and labour into output. The explanatory variables are internal and out-of-region stocks of knowledge, the latter capturing the contribution of cross-region knowledge spillovers. We construct patent stocks to proxy regional knowledge capital stocks for N=203 regions over the 1997- 2002 time period. In estimating the effects we implement a spatial panel data model that controls for the spatial autocorrelation due to neighbouring regions and the individual heterogeneity across regions. The findings provide a fairly remarkable confirmation of the role of knowledge capital contributing to productivity differences among regions, and add an important spatial dimension to the discussion, by showing that productivity effects of knowledge spillovers increase with geographic proximity. (authors' abstract)