Dissertationen zum Thema „Fgas“

Pesticides and their excessive use lead to environmental pollution. Violation of the guidelines for their use disposal of empty containers could lead to contamination of water, soil and poisoning of animals and beneficial insects. Honey bee is useful creature on our planet. Good farming depends entirely on the pollination, but whole vegetal kingdom couldn’t exist it form known and used by mankind. Therefore, rules that protect these useful creatures against inadequate use of pesticides have been developed. This study focuses on the evaluation of the possibility to use bee products as bioindicators of the state of environment. Five active substances which are components of pesticides used in the treatment of agricultural field around Tasovice village were analysed in the pollen and honey. For sample preparation QuEChERS and SPE methods were used, gas chromatography with to mass spectrometric detection was employed as final analytical technique.

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This thesis concerns about proposals were made in order to make flexible the use or application of the FGTS. It includes impact analysis over the government, firms and employees. The FGTS is an important device of public saving and it is able to led resources toward habitation, sewer and infrastructure areas. It is also a sort of contingency reserve available to the workers to use when them got fired or in others specific moments, according to the law. The enterprises face them like an extra cost related to the hiring process. So, it was studied features related to this fund - including management issues - to check the application possibilities and financials outcomes. In the conclusion we realized that FGTS is an important tool, it is not so simple to make its use flexible because the proposals are not complete enough to cover the impacts. And finally, its relevance increases in periods that private credits are reduced
A dissertação analisa as propostas de liberalização do FGTS e seus possíveis impactos sobre o governo, as empresas e os trabalhadores. O FGTS é um importante instrumento de poupança compulsória capaz de direcionar recursos para as áreas de habitação, saneamento básico e infra-estrutura. Ao mesmo tempo, é um pecúlio do trabalhador com o intuito de indenizá-lo quando de sua demissão ou em outras circunstâncias que a lei permite. Acrescente-se que, as empresas o consideram um custo adicional à contratação de trabalhadores pelo mercado formal. Assim, são estudadas as características e aplicações do Fundo, o gerenciamento dos recursos de modo a verificar as aplicações e os retornos financeiros. A conclusão é que, apesar da baixa remuneração ao trabalhador e dos custos para as empresas, o FGTS é um importante instrumento de funding que se torna ainda mais relevante em situações em que há redução do crédito privado

A functionally-graded Al(subscript)2TiO(subscript)5/ZrO(subscript)2-Al(subscript)2O(subscript)3 (AT/zirconia-alumina) composite has been successfully synthesized by an infiltration process involving an alpha-Al(subscript)2O(subscript)3-ZrO(subscript)2 (90:10 by weight) green body and a solution containing titanium chloride. The mass gain after infiltration has been used to estimate the amount of new phase introduced into the system. The phase composition character of the functionally-graded material (FGM) has been determined by x-ray diffraction. The Rietveld "whole pattern" refinement method was applied to diffraction patterns of the sample which were collected from the surface and at several depths which were made by polishing away the material. Absolute weight fraction determination using the Rietveld external standard method showed that the concentration of AT reduces linearly from the surface to the core. In contrast, the alpha-alumina content increases with depth in a complementary manner. Low level amorphous phase was also observed. Other functionally-graded microstructural profiles examined were x-ray characteristic line intensity of Ti, Ti dot-mapping, and alpha-alumina grain size. The FGM also exhibits graded character in both thermal and mechanical properties, i.e. thermal expansion, microhardness, and Young's modulus. The thermal expansion coefficient (TEC) of the FGM increased with polishing-depth and approached that of the zirconia-alumina reference sample at a depth of 0.5 mm.Relatively lower thermal expansion and softer surface layer in comparison to those of the core (TEC value of 5.9 x 10(subscript)-6 degrees celsius(subscript)-1 and microhardness of 6 GPa compared to 7.4 x 10(subscript)-6 degrees celsius(subscript)-1 and 12 GPa, respectively) render possibilities to implement the material to which thermal shock resistance surface but hard core, such as a metal melting crucible, are required. Load-dependent microhardness was obviously observed on the surface of the material but only slight dependence was observed in the core. This observation indicated that the material exhibit "quasi-ductile" surface but brittle core. In comparison to the reference specimen, the FGM displayed damage-tolerance and remarkable machinability.

Mesenchymal-epithelial interactions are pivotal for proper pancreatic growth and development. The pancreatic progenitor cells present in the early pancreatic anlagen proliferate and eventually give rise to all pancreatic cell types. The Fibroblast Growth Factor 2b (FGFR2b) high-affinity ligand Fibroblast Growth Factor 10 (FGF10) has been linked to pancreatic epithelial cell proliferation and we have previously shown that Notch signalling controls pancreatic cell differentiation via lateral inhibition. By overexpressing FGF10 under the control of the Ipf1/Pdx1 promoter in mice, we have shown that persistent FGF10 activation in the embryonic pancreas of transgenic mice perturbs pancreatic epithelial cell proliferation and also inhibits pancreatic cell differentiation by maintaining Notch activation. In the Ipf1/Fgf10 transgenic mice, the pancreatic epithelial cells are ‘locked’ in an undifferentiated progenitor-like state with sustained proliferative capacity. Collectively, our data suggest a key role for FGFR2b/FGF10 signalling in the regulation of pancreatic growth and differentiation and that FGFR2b/FGF10 signalling interact with the Notch signalling pathway. Glucose homeostasis in mammals is critically dependent on co-ordinated glucose uptake, oxidative metabolism and insulin secretion in β-cells. Although, several key genes controlling various aspects of glucose sensing, glucose metabolism, insulin expression and secretion have been identified, we know relatively little about the molecular mechanisms that induce and maintain the expression of genes required for glucose-stimulated insulin secretion (GSIS) in β-cells. Attenuation of FGFR1c signalling leads to diabetes in mice. Overexpression of FGF2, a high-affinity FGFR1c ligand, under the control of the Ipf1/Pdx1 promoter also leads to diabetes in mice. The Ipf1/Fgf2 mice present with normal endocrine and exocrine differentiation but display impaired glucose-stimulated insulin secretion (GSIS), perturbed expression of genes required for glucose sensing uptake together with oxidative metabolism and increased expression of the FGF-signalling inhibitors Spry-2 and Pyst1/MKP3 in β-cells. Thus, stringent control of FGF signalling activation appears crucial for the maintenance of the regulatory circuit that ensures proper GSIS in pancreatic β-cells and hence normoglycaemia. The Wnt family of ligands via their receptors Frizzled (Frz) have been shown to mediate mesenchymal-epithelial interactions and cell proliferation in a variety of different systems. Expression of a plethora of Wnt ligands and Frz receptors has been previously reported in the pancreas and mice missexpressing Wnt1 and Wnt5a under the Ipf1/Pdx1 promoter display severely perturbed development. Here, we show the temporal and spatial expression of Wnt4, Wnt7b and Frz3 at different stages of pancreas development. To elucidate the role of Wnt signalling in the pancreas, we overexpressed a dominant negative form of mouse Frz8 under the Ipf1/Pdx1 promoter in mice. The Ipf1/Frz8CRD mice display severe pancreatic hypoplasia demonstrating that attenuation of Wnt signalling in the pancreas leads to perturbed pancreatic growth. Nevertheless, the transgenic mice present with normal endocrine and exocrine differentiation and remain normoglycaemic. The maintenance of normoglycaemia in these mice appears to be the consequence of a relative increase in endocrine cell number per pancreatic area combined with enhanced insulin biosynthesis and insulin secretion. Collectively our data provide evidence that Wnt signalling is required pancreatic growth but not adult β-cell function.

COORDENAÇÃO DE APERFEIÇOAMENTO DO PESSOAL DE ENSINO SUPERIOR
A legislação brasileira obriga trabalhadores a pouparem parte de seus rendimentos em contas do Fundo de Garantia por Tempo de Serviço (FGTS). Essas contas rendem juros abaixo dos de mercado e têm liquidez limitada. Essa dissertação propõe um modelo para a análise dos efeitos que o FGTS causa nos rendimentos do trabalhador. Para isso, dividimos os rendimentos do trabalhador em duas porções, o salário líquido e as verbas rescisórias, sobre as quais a introdução do FGTS pode exercer efeitos distintos. Do modelo, extraímos que o FGTS diminui o salário dos trabalhadores formais e que, proporcionalmente, maior será essa diminuição quanto maior for a probabilidade de demissão do empregado. Tal resultado advém do fato de que o empregador, ao provisionar para o pagamento das verbas rescisórias no futuro, se beneficia do diferencial entre a remuneração das contas-vinculadas e os juros vigentes. Já o efeito do FGTS sobre o rendimento do trabalhador, quando se leva em conta também a expectativa das verbas rescisórias, é ambíguo. Se, por um lado, há um prejuízo para o trabalhador proveniente da baixa remuneração do saldo de sua conta, por outro, sobre todas as verbas do FGTS - depósitos mensais, resgate e multa - não incidem quaisquer tributos, para débito do empregado ou empregador. Dessa maneira, o FGTS poderia aumentar o rendimento do trabalhador. Finalmente, utilizando as modificaçõees introduzidas pela Lei Complementar 110 de 2001, que celebrou o Acordo do FGTS, encontramos alguma evidência empírica que, de fato, o FGTS diminui salários dos trabalhadores formais.
According to the Brazilian labor legislation, it is mandatory for workers to save part of their rent into Fundo de Garantia por Tempo de Serviço (FGTS) accounts. These accounts yield below-market interest rates and have a limited liquidity. This paper proposes a model to analyze the effects the FGTS legislation causes on the worker´s income. We divide the worker´s income in two portions, the liquid wages and severance payments, on which FGTS might produce different effects. From the model, we extract that the FGTS decreases formal worker´s wages and that, proportionally, the larger the probability of being fired, the larger the decrease. That result comes from the fact that, when provisioning for the severance payments in the future, the employer benefits from the difference between FGTS account returns and market interest rates. The effect of the FGTS on the worker´s total income, on the other hand, is ambiguous. The fact that all the FGTS savings and fines are exempt from taxes - for both the employer and the employee - might compensate the worker from the low returns of this mandatory savings, increasing the total worker´s income. Finally, using the 2001 FGTS Agreement changes in the legislation, we found some empirical evidence that the FGTS decreases wages of formal workers.

La traduction de certains ARNm peut s'effectuer directement par leur région 5' non traduite (5'NTR) via un IRES, alors même que la machinerie d'initiation de traduction ne peut utiliser la coiffe. Nous avons recherché des IRES dans les 5'NTR des ARNm du FGF-1, puis dans ceux de tous les autres FGFs. Les quatre transcrits du FGF-1 codent pour une seule isoforme protéique et ne différent que par leur 5'NTR A, B, C et D. Deux IRES très actifs, de 118 et 103 nucléotides respectivement, ont été caractérisés dans les 5'NTR A et C. L'analyse de l'IRES A a révélé la conservation du motif essentiel D2. Pour visualiser la tissu spécificité et les régulations in vivo, nous avons développé 2 lignées de souris transgéniques exprimant les 5'NTR A et B du FGF-1 murin. Nous avons entrepris de déterminer l'influence du type cellulaire et du taux de transcription sur des IRES viraux et cellulaires. Les résultats suggèrent un lien entre la transcription et la traduction

Abstract The mammalian metanephric kidney develops through ureteric bud branching morphogenesis and tubule formation and involves secreted inductive signals and possibly their antagonists to regulate the process. Sprouty (spry) genes encode antagonists of FGFs and the EGF signalling pathways. To get an insight to potential developmental roles of the spry genes, the expression of spry1, 2 and 4 was analyzed in developing kidney. Spry1 is expressed in the ureteric bud, and spry2 and 4 in the ureteric bud, the kidney mesenchyme and the nephrons deriving from it suggesting developmental roles for the sprys in kidney development. Spry function was addressed in vivo in the kidney by targeting hspry2 expression to the ureteric bud with a Pax2 promoter. Hspry2 expression led to development of small, ectopic and cystic kidneys. Ureter branching was reduced and there was less glomeruli in a smaller kidney compared to the wild type controls. Spry2 may antagonize signalling of FGF2 and lead to changes in FGFR1 and FGFR3 expression. In organ culture ectopic FGFs restored ureteric branching of the hSpry2 transgenic kidneys suggesting that hSpry2 may antagonize FGF signalling in embryonic kidney. In addition to changes in FGFs, hspry2 expression also lead to downregulation of GDNF and BMP4. We conclude that the Sprouty-FGFs-FGFR signaling is important for kidney development. Wnt2b is a recently identified member of the Wnt family of secreted growth factors, but its function in organogenesis is unknown. In the kidney Wnt2b is localized to the perinephric mesenchymal cells at the initiation of organogenesis. Wnt2b signalling supported ureteric bud growth and branching in vitro. Ureteric bud that was co-cultured with Wnt2b expressive cells or incubated with a known Wnt pathway regulator lithium, and then recombined with isolated kidney mesenchyme led to recovery of the expression of some ureteric epithelial marker genes and reconstitution of early kidney development. Hence, Wnt2b signalling is critical for induction of ureteric branching in vitro. Type XVIII collagen is a matrix molecule and may be involved in Wnt signalling. Roles of type XVIII collagen in kidney and lung organogenesis was analysed. Type XVIII collagen expression correlated with the differences in epithelial branching in both of these organs and its expression in the epithelial tissue was mutually exclusive. In recombinants of ureteric bud and lung mesenchyme, type XVIII collagen expression pattern shifted from kidney to lung type and was accompanied by a shift in epithelial Sonic Hedgehog (Shh) expression and by ectopic lung Surfactant Protein C in the ureteric bud. Blocking of type XVIII collagen function prevented ureteric development with lung mesenchyme and associated with reduction in the expression of Wnt2. Taken together, the findings suggest critical roles for Sprouty2, Wnt2b and type XVIII collagen in controlling pattern formation and the mode of ureteric bud branching in the embryonic kidney.

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The evolution of deep submicron technologies allows the development of increasingly complex Systems on a Chip. However, this evolution is rendering less viable some well-established design practices. Examples of these are the use of multipoint communication architectures (e. g. busses) and designing fully synchronous systems. In addition, power dissipation is becoming one of the main design concerns due e. g. to the increasing use of mobile products such as PDAs, mobile phones and laptop computers. An alternative to overcome the design practices becoming unviable is adopting Networks on Chip (NoCs) communication architectures supporting globally asynchronous locally synchronous (GALS) system design. This work has as main goal the development of features to support the design of GALS systems in FPGAs devices. The selection of FPGAs as target architecture occurred because several of these commercial devices already contain features supporting the design of GALS systems, such as the availability of multiple independent clock domains. Also, FPGAs are used in many scenarios as an important verification step in the design of complex integrated circuits. This works explores three development axes for enabling GALS design in FPGAs. Each one led to its own set of usable, practical results. First, there is the proposition and design of a macro block library of asynchronous devices for FPGAs. The cells of this library can be used to create compact and efficient non-synchronous modules in FPGAs. Second, after comparing a set of approaches for developing asynchronous interfaces in FPGAs and ASICS, the SCAFFI family of asynchronous interfaces was proposed. SCAFFI allows that modules operating in distinct clock domains interconnect to each other seamlessly. Third, two NoC routers supporting the GALS systems were proposed and validated: Hermes GALS (Hermes-G) and Hermes GALS Low Power (Hermes-GLP). The Hermes-GLP router, besides supporting the development of GALS systems, takes advantage of the GALS design style to reduce power dissipation in the routers. The way to achieve this is to add frequency switching mechanisms to the latter. Some circuits have been employed as case studies to validate the two first development axes, including an RSA cryptography core and combinational and pipeline multipliers. The most relevant strategic contribution of this work is the generation of a basic infrastructure for the design of GALS systems in FPGAs.
Devido à evolução das tecnologias submicrônicas, hoje é possível o desenvolvimento de sistemas cada vez mais complexos dentro de um chip. Entretanto, esta evolução está inviabilizando algumas práticas de projeto tradicionais. O uso de comunicação intrachip multiponto, exemplificada por arquiteturas de barramento, e o desenvolvimento de sistemas completamente síncronos são exemplos destas práticas. Adicionalmente, a dissipação de potência está se tornando uma das principais restrições de projeto devido, por exemplo, ao aumento do uso e relevância de produtos baseados em baterias como PDAs, telefones celulares e computadores portáteis. Uma alternativa para superar estas práticas de projeto que estão perdendo viabilidade é a utilização de redes de comunicação intrachip que dêem suporte ao desenvolvimento de sistemas globalmente assíncronos e localmente síncronos (GALS). Este trabalho tem como principal alvo o desenvolvimento de suporte para o projeto utilizando o paradigma GALS em FPGAs. FPGAs foram selecionados como arquitetura alvo porque dispositivos comerciais atuais já possuem parte da infra-estrutura para dar suporte a sistemas GALS, incluindo múltiplos domínios de relógio em um único dispositivo. Também, FPGAs são dispositivos essenciais na etapa de verificação de projetos complexos que serão mais tarde sintetizados como circuitos integrados dedicados. Ao longo do trabalho, três eixos de viabilização de projeto GALS em FPGAs foram abordados, cada um gerando resultados práticos. Primeiro, foi proposta e desenvolvida uma biblioteca de macro blocos para dar suporte ao projeto de dispositivos assíncronos em FPGAs de forma compacta e eficiente. Segundo, após uma fase de comparação de interfaces assíncronas sugeridas na literatura para FPGAs e ASICs, foi proposta e validada SCAFFI, uma família de interfaces assíncronas para comunicação de módulos síncronos com relógios distintos. Terceiro, dois tipos de roteadores de redes intrachip com suporte para o projeto de sistemas GALS foram propostos e validados: Hermes GALS (Hermes-G) e Hermes GALS Low Power (Hermes-GLP). O roteador Hermes-GLP, além de dar suporte ao desenvolvimento de sistemas GALS, aproveita as características desse estilo de projeto para reduzir a dissipação de potência nos roteadores. Isto se dá através do emprego de mecanismos de chaveamento de freqüência internamente ao roteador. Alguns circuitos foram usados como estudos de caso para validar as duas primeiras estruturas propostas, exemplos sendo um núcleo de criptografia RSA e multiplicadores combinacionais e pipeline. A contribuição mais importante deste trabalho foi a geração de uma infra-estrutura básica para projeto de sistemas GALS em FPGAs.

Airframes operating in the hypersonic regime are subjected to complex structural and thermal loads. Structural loads are a result of aggressive high G maneuvers, rapid vehicle acceleration and deceleration, and dynamic pressure, while thermal loads are a result of aerodynamic heating. For such airframes, structural members are typically constructed from steel, titanium and nickel alloys. However, with most materials, rapid elevations in temperature lead to undesirable changes in material properties. In particular, reductions in strength and stiffness are observed, along with an increase in thermal conductivity, specific heat and thermal expansion. Thus, hypersonic airframes are typically designed with external insulation, active cooling or a thermal protection system (TPS) added to the structure to protect the underling material from the effects of temperature. Such thermal protection may consist of adhesively bonded, pinned, and bolted thermal protection layers over exterior panels. These types of attachments create abrupt changes in thermal expansion and stiffness that make the structure susceptible to cracking and debonding as well as adding mass to the airframe. One of the promising materials concepts for extreme environments that was introduced in the past is the so-called Spatially Tailored Advanced Thermal Structures (STATS). The concept of STATS is rooted in functionally graded materials (FGMs), in which a directional variation of material properties exists. These materials are essentially composites and consist of two or more phases of distinct materials in which the volume fractions of each phase continuously change in space. Here, the graded material will serve a dual-purpose role as both the structural/skin member and thermal management with the goal of reducing the weight of the structure while maintaining structural soundness. This is achieved through the ability to tailor material properties to create a desired or enhanced thermomechanical response through spatial variation (e.g. grading). The objective of this study is to present a computational framework for modeling and evaluating the thermomechanical response of STATS and FGMs for highly maneuverable hypersonic (Mach > 5) airframes. To meet the objective of this study, four key steps have been defined to study the thermomechanical response of such materials in extreme environments. They involve: (1) modeling of graded microstructures; (2) validation of analytical and numerical modeling techniques for graded microstructures; (3) determination of effective properties of variable composition composites; (4) parametric studies to evaluate the performance of FGMs for use in the hypersonic operating environment; (5) optimization of the material spatial grading in hypersonic panels aiming to improve the thermomechanical performance. Modeling of graded microstructures, representing particulate reinforced FGMs, has been accomplished using power law distribution functions to specify the spatial variation of the constituents. Artificial microstructures consisting of disks and spheres have been generated using developed algorithms. These algorithms allow for the creation of dense packing fractions up to 0.61 and 0.91 for 2D and 3D geometry, respectively. Effective properties of FGMs are obtained using micromechanics models and finite element analysis of representative volume elements (RVEs). Two approaches have been adopted and compared to determine the proper RVE for materials with graded microstructures. In the first approach, RVEs are generated by considering regions that have a uniform to slow variation in material composition (i.e., constant volume fraction), resulting in statistically homogenous piecewise RVEs of the graded microstructure neglecting interactions from neighboring cells. In the second approach, continuous RVEs are generated by considering the entire FGM. Here it is presumed that modeling of the complete variation in a microstructure may influence the surrounding layers due to the interactions of varying material composition, particularly when there is a steep variation in material composition along the grading direction. To determine these effects of interlayer interactions, FGM microstructures were generated using three different types of material grading functions, linear, quadratic and square root, providing uniform, gradual and steep variations, respectively. Two- and three-dimensional finite element analysis was performed to determine the effective temperature-dependent material properties of the composite over a wide temperature range. The outcome of the computational analysis show that the similar effective properties are obtained by each of the modeling approaches. Furthermore, the obtained computational results for effective elastic, thermal, and thermal expansion properties are consistent with the known analytical bounds. Resulting effective temperature-dependent material properties were used to evaluate the time-dependent thermostructural response and effectiveness of FGM structural panels. Structural panels are subjected to time- and spatial-dependent thermal and mechanical loads resulting from hypersonic flight over a representative trajectory. Mechanical loads are the by-product of aggressive maneuvering at high air speeds and angles of attack. Thermal loads as a result of aerodynamic heating are applied to the material systems as laminar, turbulent and transitional heat flux on the outer surface. Laminar and turbulent uniform heat fluxes are used to evaluate the effectiveness of FGM panels graded in the through-thickness direction only. Transitional heat fluxes are used to evaluate the effectiveness of FGMs graded in two principal directions, e.g., through-thickness and the surface parallel to flow. The computational results indicate that when subjected to uniform surface heat flux, the graded material system can eliminate through-thickness temperature gradients that are otherwise present in traditional thermal protection systems. Furthermore, two-dimensional graded material systems can also eliminate through-thickness temperature gradients and significantly reduce in-plane surface temperature gradients when subjected to non-uniform surface aerodynamic heating.

A functionally-graded Al(subscript)2TiO(subscript)5/ZrO(subscript)2-Al(subscript)2O(subscript)3 (AT/zirconia-alumina) composite has been successfully synthesized by an infiltration process involving an alpha-Al(subscript)2O(subscript)3-ZrO(subscript)2 (90:10 by weight) green body and a solution containing titanium chloride. The mass gain after infiltration has been used to estimate the amount of new phase introduced into the system. The phase composition character of the functionally-graded material (FGM) has been determined by x-ray diffraction. The Rietveld "whole pattern" refinement method was applied to diffraction patterns of the sample which were collected from the surface and at several depths which were made by polishing away the material. Absolute weight fraction determination using the Rietveld external standard method showed that the concentration of AT reduces linearly from the surface to the core. In contrast, the alpha-alumina content increases with depth in a complementary manner. Low level amorphous phase was also observed. Other functionally-graded microstructural profiles examined were x-ray characteristic line intensity of Ti, Ti dot-mapping, and alpha-alumina grain size. The FGM also exhibits graded character in both thermal and mechanical properties, i.e. thermal expansion, microhardness, and Young's modulus. The thermal expansion coefficient (TEC) of the FGM increased with polishing-depth and approached that of the zirconia-alumina reference sample at a depth of 0.5 mm.
Relatively lower thermal expansion and softer surface layer in comparison to those of the core (TEC value of 5.9 x 10(subscript)-6 degrees celsius(subscript)-1 and microhardness of 6 GPa compared to 7.4 x 10(subscript)-6 degrees celsius(subscript)-1 and 12 GPa, respectively) render possibilities to implement the material to which thermal shock resistance surface but hard core, such as a metal melting crucible, are required. Load-dependent microhardness was obviously observed on the surface of the material but only slight dependence was observed in the core. This observation indicated that the material exhibit "quasi-ductile" surface but brittle core. In comparison to the reference specimen, the FGM displayed damage-tolerance and remarkable machinability.

La purification des facteurs de croissance du fibroblaste (fgf) acide et basique chez le poulet au cours du developpement embryonnaire a permis de confirmer la grande conservation des fgf au cours de l'evolution. Le photorecepteur est la cellule qui contient la plus grande activite mitogenique specifique en fgf

Les FGFs ou Fibroblast Growth Factors constituent une large famille de facteurs de croissance regroupant 23 membres chez la souris. Ils contribuent, par liaison spécifique sur des récepteurs transmembranaires à activité tyrosine kinase (notés FGFR), à de nombreux processus physiologiques et pathologiques tels que l'embryogenèse, l'organogenèse, la spermatogenèse, l'hématopoi͏̈èse, l'angiogenèse et la lymphangiogenèse physiologique ou tumorale. Leurs fonctions biologiques ont pu être appréhendées ces dernières années par utilisation de différents outils de biologie moléculaire. Cependant, les invalidations des gènes codant pour ces facteurs ou pour leurs récepteurs n'ont apporté que très peu d'informations à cause soit de létalités précoces soit d'une absence de phénotype due à une compensation fonctionnelle. Il a donc été entrepris d'élucider leurs différentes fonctions en surexprimant un récepteur tronqué pour ses domaines tyrosine kinase. Cette approche définie sous le terme de ± récepteur dominant négatif ou FGFR-DN α permet de fixer les facteurs FGFs spécifiques à un récepteur, mais ne permet plus d'activer les cascades de signalisation intracellulaires. L'expression d'une forme tronquée du FGFR-1 associée à la technique de transgenèse classique ciblée à un tissu, l'épithélium rétinien pigmenté, a permis d'appréhender l'influence des FGFs lors de la vascularisation développementale oculaire d'une part, et lors de l'angiogenèse tumorale d'autre part. L'utilisation de cellules de gliome de rat surexprimant une forme dominante négative du FGFR-2 a également permis de définir le rôle exercé par les FGFs lors de la lymphangiogenèse tumorale. Il en ressort que ces FGFs sont nécessaires : Þ A l'angiogenèse choroi͏̈dienne et rétinienne lors la vascularisation oculaire, Þ Au développement de cancers par induction de leur angiogenèse à partir d'une taille tumorale critique, Þ A la croissance de vaisseaux lymphatiques tumoraux.

L'objet de notre travail a porte sur deux cytokines: le fibroblast growth factor et l'interleukine 6. Nous avons choisi d'etudier les themes suivants. Plusieurs travaux recents evoquant le role du fgf dans le processus de cicatrisation tissulaire, nous avons estime qu'il etait important de rechercher une eventuelle participation du fgf dans la proliferation vitreoretinienne. Nous avons montre la presence de quantites importantes de fgf dans les membranes epiretiniennes. En raison de ses proprietes angiogenes, le fgf etait un candidat de choix dans l'initiation de la neovascularisation retinienne. In vitro, nous avons montre que le fgf, synthetise par les cellules endotheliales des capillaires retiniens, regule leur proliferation, etape importante de l'angiogenese retinienne. Nous basant sur le role du fgf dans le fonctionnement de l'epithelium pigmentaire et du photorecepteur, nous avons recherche des anomalies du complexe fgf-recepteur dans un modele animal de retinopathie pigmentaire. Nous avons ainsi montre une diminution du nombre de recepteurs au fgf chez le rat pathologique. Nous avons enfin demontre que l'il6, cytokine inflammatoire, etait un mediateur important de la reaction inflammatoire post-operatoire et de la cicatrisation corneenne. A la suite de nos observations, l'implication directe du fgf et de l'il6 n'a pas ete formellement demontree mais reste tres probable. Nos resultats renforcent l'idee actuelle du role majeur joue par les cytokines dans diverses maladies, laissant entrevoir par la de nouvelles alternatives therapeutiques

Un estudiante universitario de primera generación (EUPG, First Generation College Student, FGCS) se define como una persona cuyos padres tienen escaso conocimiento acerca de la educación superior y el objetivo de esta etnografía es mostrar como se utiliza esta categoría social en una universidad del suroeste de los Estados Unidos de América. El primer capítulo sirve de introducción. El segundo capítulo ubica el estudio dentro de la etnografía, viéndola como una perspectiva en las ciencias sociales. Se traza un mapa conceptual de numerosas referencias relacionadas a la etnografía como método y presenta los elementos necesarios para hacer una "etnografía informada por la etnometodología". El tercer capítulo realiza una revisión de la literatura acerca de la categoría social de EUPG y el trabajo académico con ésta desde dentro y fuera del los confines de la investigación científica. De ahí, siguen dos capítulos donde el Membership Categorization Analysis (MCA, análisis de pertenencia categórica) se aplica a varios tipos de datos etnográficos. En el primero se analiza la transcripción de un DVD de marketing educativo, un artefacto institucional que presenta las experiencias de un grupo de EUPGs. Para el segundo capítulo de análisis se toman los apuntes del libro de campo en combinación con unos documentos que fueron recogidos durante la estancia etnográfica. Durante el análisis del DVD, los documentos, y de los apuntes del diario de campo aparecieron varias categoríasrelacionadas a la categoría social de EUPG. Éstas surgen en acontecimientos y el MCA sirve para pensar la extensión y la penetración del "identity work" (trabajo de identidad) que se da en el ámbito cotidiano de la educación superior. El concepto de membership knowledge (conocimiento de pertenencia) sirve para poner en primer plano las categorías de interacciones vividas, las que se constituyen por los propios integrantes de las interacciones. En los conjuntos de datos presentados en esta tesis empezamos a ver que el EUPG también pertenece a varias minorías, sea por etnia, raza, o sexo. Esto sucede en el DVD donde se les pide a unos estudiantes que hablen de su experiencia como los primeros de su familia en el mundo de la educación superior. También queda patente en el protagonismo que se le da a un listón que ciertas personas se añaden a la vestimenta académica para la ceremonia oficial de graduación. Las diferentes categorías también surgen en una solicitud a una beca estatal, escrita por los directores de un programa para la formación de EUPGs como trabajadores sociales. En ella aparece la categoría de estudiante tradicional pero aparece de manera ubicua, al igual que en los demás conjuntos, así como en la revisión de la literatura del tercer capítulo. A raíz del análisis de unas reflexiones que toman como referencia una interacción que ocurrió entre un niño y unos adultos en la universidad surge el cuarto conjunto de datos. Es una muestra "en acción" de las políticas universitarias en torno a varios tipos de diferencias identificadas a lo largo de esta investigación. En las conclusiones se abarcan tres aspectos básicos que aparecieron a través de toda la investigación: a) apuntes biográficos que describen por qué llegó a interesarme el sujeto de esta etnografía en relación al conocimiento producido por nuestras disciplinas y su expresión a través de una variedad de tecnologías del ser; b) la modalidad metodológica de una etnografía informada por la etnometodología que es capaz de revelar las categorías que emergen en interacciones cotidianas; y c) el uso instrumental del conocimiento que producimos en las ciencias sociales. Como tal, los resultados de este estudio se ofrecen como una oportunidad más para pensar nuestras formas de vida.
Generation College Student (FGCS) is defined as a person whose parents have little knowledge about higher education and the objective of this ethnography is to show how this social category is used at a university in the southwest of the United States of America. The first chapter serves as an introduction. The second chapter situates the study within ethnography, approached as a perspective in the social sciences. It offers a conceptual mapping of a number of ethnography as a method references and presents the necessary elements for doing an "ethnomethodologically informed ethnography". The third chapter is a literature review of the FGCS social category and the academic work done on it from within and outside of the confines of scientific research. What follows are two chapters devoted to the Membership Categorization Analysis (MCA) of a variety of ethnographic data. The first one analyses the transcript of a educational marketing DVD, an institutional artefact that presents the experiences of a group of FGCSs. The second chapter is an analysis of field notes in combination with documents that were gathered throughout the ethnography. Many categories appeared in relation to the social category of FGCS during the analysis of the DVD, the documents and the field notes. These are categories that emerge in events and MCA helps us think about the extent and pervasiveness of the "identity work" the occurs in the day-to-day activities of higher education. The concept of membership knowledge helps foreground the categories of lived interactions, the ones that get constituted by interaction members themselves. In the data sets presented in this dissertation we begin to see that FGCS also pertains to a variety of minorities in terms of ethnicity, race and sex. This happens in the DVD where a group of students are asked to talk about their experience as the first in their family to enter the world of higher education. This is also evident in the prominence given to a sash that certain students add to their academic regalia for the official graduation ceremony. The different categories also arise in a state grant application, written by the directors of a program to prepare FGCSs as social workers. It is in this document that the traditional student category appears, but in a ubiquitous manner and similar to how it arises in the rest of the data sets, as well as in the literature review of the third chapter. The subject of a fourth data set is an analysis of some reflections written in reference to an interaction that occurred between a child and some adults at the university. It shows university policies "in action" using various types of the differences identified throughout this study. The conclusions cover three basic aspects that appeared throughout the whole study: a) biographical notes the describe why I became interested in this subject of study in relation to the production of knowledge by our disciplines and their expression through a variety of technologies of the self; b) the methodological modality of an ethnomethodologically informed ethnography that is able to reveal the categories that emerge in quotidian interactions; and c) the instrumentality of the knowledge we produce in the social sciences. As such, the results of this study offer one more opportunity to think about our forms of life.

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Devido ? evolu??o das tecnologias submicr?nicas, hoje ? poss?vel o desenvolvimento de sistemas cada vez mais complexos dentro de um chip. Entretanto, esta evolu??o est? inviabilizando algumas pr?ticas de projeto tradicionais. O uso de comunica??o intrachip multiponto, exemplificada por arquiteturas de barramento, e o desenvolvimento de sistemas completamente s?ncronos s?o exemplos destas pr?ticas. Adicionalmente, a dissipa??o de pot?ncia est? se tornando uma das principais restri??es de projeto devido, por exemplo, ao aumento do uso e relev?ncia de produtos baseados em baterias como PDAs, telefones celulares e computadores port?teis. Uma alternativa para superar estas pr?ticas de projeto que est?o perdendo viabilidade ? a utiliza??o de redes de comunica??o intrachip que d?em suporte ao desenvolvimento de sistemas globalmente ass?ncronos e localmente s?ncronos (GALS). Este trabalho tem como principal alvo o desenvolvimento de suporte para o projeto utilizando o paradigma GALS em FPGAs. FPGAs foram selecionados como arquitetura alvo porque dispositivos comerciais atuais j? possuem parte da infra-estrutura para dar suporte a sistemas GALS, incluindo m?ltiplos dom?nios de rel?gio em um ?nico dispositivo. Tamb?m, FPGAs s?o dispositivos essenciais na etapa de verifica??o de projetos complexos que ser?o mais tarde sintetizados como circuitos integrados dedicados. Ao longo do trabalho, tr?s eixos de viabiliza??o de projeto GALS em FPGAs foram abordados, cada um gerando resultados pr?ticos. Primeiro, foi proposta e desenvolvida uma biblioteca de macro blocos para dar suporte ao projeto de dispositivos ass?ncronos em FPGAs de forma compacta e eficiente. Segundo, ap?s uma fase de compara??o de interfaces ass?ncronas sugeridas na literatura para FPGAs e ASICs, foi proposta e validada SCAFFI, uma fam?lia de interfaces ass?ncronas para comunica??o de m?dulos s?ncronos com rel?gios distintos. Terceiro, dois tipos de roteadores de redes intrachip com suporte para o projeto de sistemas GALS foram propostos e validados: Hermes GALS (Hermes-G) e Hermes GALS Low Power (Hermes-GLP). O roteador Hermes-GLP, al?m de dar suporte ao desenvolvimento de sistemas GALS, aproveita as caracter?sticas desse estilo de projeto para reduzir a dissipa??o de pot?ncia nos roteadores. Isto se d? atrav?s do emprego de mecanismos de chaveamento de freq??ncia internamente ao roteador. Alguns circuitos foram usados como estudos de caso para validar as duas primeiras estruturas propostas, exemplos sendo um n?cleo de criptografia RSA e multiplicadores combinacionais e pipeline. A contribui??o mais importante deste trabalho foi a gera??o de uma infra-estrutura b?sica para projeto de sistemas GALS em FPGAs.

Les fibroblast growth factors (fgfs) acide (fgfa) et basique (fgfb) sont des facteurs de croissance qui induisent la proliferation cellulaire in vivo et in vitro et possedent de nombreuses autres proprietes biologiques. Ces proprietes sont modulees par l'heparine pour laquelle ils ont beaucoup d'affinite. Elle les stabilise, les protege contre des denaturations thermiques et proteolytiques. Leur mode d'action passe par des interactions avec des sites de haute affinite membranaires et des sites de basse affinite constitues par les heparanes sulfates qui servent de lieu de stockage des fgfs. Ils peuvent etre liberes sous forme bioactive pour assurer des fonctions biologiques. Nous montrons dans ce travail que les biomateriaux, polymeres solubles et insolubles peuvent mimer le role que joue l'heparine vis-a-vis des fgfs. Les polymeres solubles etudies sont de trois types, dextranes solubles portant des substitutions variables, polymeres polyelectrolytiques, et un dextrane sulfate. Les dextranes substitues et le dextrane sulfate stabilisent, potentialisent et protegent les proprietes biologiques des fgfs. Les protections assurees par les polymeres polyelectrolytiques sont fonction d'unites qu'ils comportent. Les polymeres insolubles, polystyrenes greffes avec des fonctions sulfonate et sulfamide d'acide amine serine fixent le fgfb radiomarque, et lorsqu'ils sont recouverts de fibronectine, permettent la croissance des cellules endotheliales de cornee bovine. Le fgfb fixe sur les resines est biodisponible pour les cellules. Les resultats obtenus peuvent trouver de nombreuses applications dans le domaine pharmacologique, chirurgical et cosmetologique

PINHEIRO, Aurélio Ferreira. Modelos univariados de séries temporais para previsões de curto prazo da arrecadação nacional do FGTS. 87f. Dissertação (mestrado profissional) - Programa de Pós Graduação em Economia, CAEN, Universidade Federal do Ceará, Fortaleza, 2004.
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To formulate statistical models directed to the accomplishment of forecasts in short term (up to 12 steps to the front) on the collection of the FGTS, with sights to contribute with the precision of the estimates contained in its annual budget is the objective of the present research. The resources of the FGTS constitute one significant funding it federal government to finance workmanships of habitation, sanitation and infrastructure, generating of great economic and social impact. Caixa Econômica Federal is the operator agent of the FGTS, for that it has the responsibility to manage the collection of its contributions, under the supervision of the Advice Custodian of the FGTS - CCFGTS and the Ministry of the Cities, managing agency of the applications and responsible for the elaboration of the Annual Budget. To each end of year forecasts on the collection of the FGTS with sights are made to subsidize the budgetary and financial planning of its resources. Such forecasts have a crucial importance, in the measure where small margins of error can generate expressives distortions, considering the volume of the involved values in absolute terms, situation that demands one high degree of precision. For analysis and modeling of the series of collection of the FGTS the models of exponential smoothing and ARIMA had been used, beyond the technique of combination of forecasts. The results of the done forecasts to leave of these models had been better that the constant in the budget of the FGTS, what it suggests the necessity of revision of the techniques applied in the current model.
Formular modelos estatísticos voltados à realização de previsões no curto prazo (até 12 passos à frente) sobre a arrecadação do FGTS, com vistas a contribuir com a precisão das estimativas contidas em seu orçamento anual é o objetivo da presente pesquisa. Os recursos do FGTS constituem um funding significativo para o governo federal financiar obras de habitação, saneamento e infra-estrutura, geradoras de grande impacto econômico e social. A Caixa Econômica Federal é o agente operador do FGTS, pelo que tem a responsabilidade de administrar a arrecadação de suas contribuições, sob a supervisão do Conselho Curador do FGTS – CCFGTS e do Ministério das Cidades, órgão gestor das aplicações e responsável pela elaboração do Orçamento Anual. A cada final de ano são feitas previsões sobre a arrecadação do FGTS com vistas a subsidiar o planejamento orçamentário e financeiros de seus recursos. Tais previsões tem uma importância crucial, na medida em que pequenas margens de erro podem gerar distorções expressivas, considerando o volume dos valores envolvidos em termos absolutos, situação que exige um alto grau de precisão. Para análise e modelagem das séries de arrecadação do FGTS foram utilizados os modelos de alisamento exponencial e ARIMA, além da técnica de combinação de previsões. Os resultados das previsões feitas a partir destes modelos foram melhores que as constante no orçamento do FGTS, o que sugere a necessidade de revisão das técnicas aplicadas no modelo atual.

Esta dissertação trata do nascimento e evolução do Fundo de Garantia do Tempo de Serviço (FGTS), seu momento histórico, sua evolução, o tratamento constitucional dado ao instituto na Constituição de 1988 e a sua efetividade através da lei 8.036/90. Analisa o tema da proteção do trabalho, demissão sem justa causa, no mundo contemporâneo, com passagens por vários países dentro de um contexto de plena globalização. A proteção do emprego no Brasil como conhecemos, através de um Fundo com natureza jurídica híbrida, com função de direito social do trabalhador no momento de sua despedida e a aplicação dos recursos das contas vinculadas em programas habitacionais, de saneamento ambiental e infraestrutura tornam o FGTS um Fundo de natureza única no mundo todo. Os investimentos realizados com recursos do FGTS são imprescindíveis para o desenvolvimento da economia brasileira, com reflexos diretos na geração de empregos e na melhoria do bem estar social, não só dos trabalhadores filiados ao sistema FGTS, mas a toda população brasileira. A Ação Direta de Inconstitucionalidade 5090/DF trata da inconstitucionalidade do índice de correção do FGTS, a Taxa Referencial (TR), informando que o índice não é apto a representar o fenômeno inflacionário e por isso deve ser considerada sua inconstitucionalidade, por ferir o direito de propriedade (art.5º, XXII, CF), a moralidade administrativa (art. 37, X) e o próprio Fundo de Garantia do Tempo de Serviço (art. 7º, III). A proposta legislativa que encerra o trabalho deve levar em consideração a natureza jurídica polivalente do FGTS, atendendo tanto quanto possível aos interesses dos cotistas do Fundo e ao mesmo tempo os tomadores de empréstimos com recursos do FGTS, não quebrando o equilíbrio econômico financeiro do Fundo.
This dissertation deals with Guarantee Fund for Time of Service (FGTS) origin and evolution, its historical moment, the treatment conferred by Brazilian Constitution of 1988 and the effectiveness provided by the law 8.036/90. It analyses employment protection, unjustified resignation on the contemporary world, according the law of many countries inserted in the context of globalization. Brazilian employment protection policy by means of a hybrid juridical nature fund, the function as laid off worker\'s social right, and investment in housing programs, environmental sanitation and infrastructure projects make FGTS a fund with unique characteristics. FGTS resources investments are indispensable to Brazilian economy development, resulting in job creation and welfare improvement for whole Brazilian population. The Direct Action of Unconstitutionality 5090/DF deals with unconstitutionality of FGTS correction index, called \"referential tax\" (TR), alleging the unfitness of this index in representing the inflationary phenomenon as cause to declare its unconstitutionality, in reason of disagreement with property right (art. 5º, XXIII, CF), administrative morality (art. 37, X), and the Guarantee Fund for Time of Service itself (art. 7º, III). The legislative proposal at the end of this dissertation considers the polyvalent juridical nature of FGTS, attending the interests of fund quotaholders and FGTS resources borrowers, and preserving its economic-financial balance.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
A compreensão dos mecanismos moleculares controladores do desenvolvimento, função e regressão do CL bovino é necessária para o aprimoramento da manipulação hormonal ovariana. Fortes evidências sugerem o envolvimento de fatores de crescimento fibroblástico (FGFs) na regulação do crescimento e regressão do CL. “Splicing” alternativo de 4 genes formam sete subtipos de FGFRs com afinidade variável por diferentes FGFs. Os membros da subfamília do FGF8 (FGF8, 17 e 18) ativam eficientemente o FGFR3C e 4 e podem atuar em cooperação nos tecidos que expressão estes receptores. O objetivo deste trabalho foi determinar o padrão de expressão dos FGFRs e dos membros da subfamília do FGF8 no CL bovino (CL). Os CLs foram obtidos de ovários de abatedouro e classificados em 4 estádios de desenvolvimento (estádio/1= corpo hemorrágico, estádio/2= CL em desenvolvimento, estádio/3= CL maduro/início da luteólise funcional e estádio/4= luteólise estrutural). O RNAm foi mensurado por PCR semiquantitativo e a proteína localizada por imunohistoquímica. A expressão do RNAm codificante das isoformas ‘B’ e ‘C’ de FGFR1 e FGFR2 foi detectada no CL bovino por PCR associado à eletroforese e foi acompanhada pela localização da proteína nas pequenas e grandes células luteínicas. A expressão do RNAm do FGFR1C e 2C não variou durante o desenvolvimento luteínico, distintamente a expressão do FGFR1B aumentou no estádio 3. Embora os FGFRs 3B, 3C e 4 tenham sido detectados de forma inconsistente por PCR associado à eletroforese, o RNAm do FGFR3C e FGFR4 foram detectados por PCR em tempo real em todos os estádios do desenvolvimento luteínico. O RNAm do FGF18 foi detectado por PCR em tempo real em todos os estádios do desenvolvimento luteínico e sua abundancia do RNAm do FGF18 foi maior no estádio 3 comparado com os estádios 1, 2 e 4. Em contraste, os RNAm do FGF8 e 17...
The molecular mechanisms controlling the development, function and regression of the bovine corpus luteum are necessary for the improvement of reproductive biotechnologies. Strong evidence suggests the involvement of fibroblast growth factors (FGFs) in the regulation of growth, and regression of the corpus luteum (CL). Alternative splicing of 4 genes give rise to seven subtypes of FGFRs with varying affinity for different FGFs. FGF8 subfamily members (FGF8, 17 and 18) efficiently activate FGFR3C and FGFR4 and may act in cooperation in tissues expressing these receptors. The objective of the present study was to determine the pattern of expression of FGF8 subfamily members and FGFRs in the bovine CL. Bovine CLs were obtained from abattoir ovaries and classed into four stages of development (stage 1= corpus hemorragicum, stage 2= developing CL, stage 3= mature/early functional luteolysis CL, and stage 4= structural luteolysis). Expression of mRNA was measured by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) followed by gel analysis (FGFR1-4) and real time RT-PCR (FGF8 subfamily members, FGFR3C and FGFR4) and proteins were localized by immunohistochemistry. Expression of mRNA encoding ‘B’ and ‘C’ spliced forms of FGFR1 and FGFR2 was readily detected in the bovine CL and was accompanied by isoform non-specific protein localization. FGFR1C and FGFR2C mRNA expression did not vary throughout CL lifespan, whereas FGFR1B was upregulated in the mature CL (stage III). FGFR3B, FGFR3C and FGFR4 expression was inconsistent in the bovine CL as assessed by PCR associated with gel analysis. FGF18, FGFR3C and FGFR4 mRNA was detected by real time PCR in all four developmental stages, and FGF18 mRNA abundance was higher in stage 3 (2.89  0.05; mean ± SEM) compared with stages 1 (0.3  0.27), 2 (0.56  1.27) and 4 (0.99  0.32). The m RNA expression ... (Complete abstract click electronic access below)

Pseudallescheria es un género de ascomicetos caracterizado por ser polimórfico, ya que pueden presentar hasta tres formas morfológicamente diferentes, una forma sexual o teleomorfo y dos formas asexuales o anamorfos (sinanamorfos). Estas dos formas asexuales se clasifican en los géneros anamórficos Scedosporium y Graphium. Pseudallescheria boydi es la especie más importante del género debido a que es considerado un hongo patógeno emergente capaz de producir infecciones graves especialmente en pacientes inmnusuprimidos. Hasta la presente tesis, el anamorfo de P. boydii era Scedosporium apiospermum.
En los últimos años, P. boydii ha sido objeto de diversos estudios moleculares que han mostrado su elevada variabilidad intraespecífica. Otros trabajos han puesto de relieve su variabilidad en cuanto a la respuesta a los antifúngicos así como la diferente virulencia que existe entre sus cepas. Todo ello hacía suponer que en lugar de una sola especie nos hallábamos frente a un complejo de especies. Por esta razón decidimos realizar un estudio molecular y morfológico utilizando numerosas cepas tanto clínicas como ambientales y de diferentes países. Gran parte de las cepas ambientales fueron aisladas por nosotros con la utilización del medio selectivo DRBC con benomilo. El análisis de secuencias parciales del gen de la β-tubulina (dos loci) y la calmodulina y las regiones ITS del ADNr demostraron que P. boydii es un complejo de especies. El análisis combinado de las secuencias de los 4 loci nos permitió la distinción de 8 especies filogenéticas agrupadas en 4 clados diferentes. Los clados 1 y 2 fueron descritos como las nuevas especies Scedosporium aurantiacum y Pseudallescheria minutispora, respectivamente. El clado 5 consistió en 4 subgrupos incorporando las cepas tipos de P. boydii Pseudallescheria angusta, Pseudallescheria ellipsoidea y Pseudallescheria fusoidea. En el caso de los clados 3 y 4 fueron considerados únicamente como especies filogenéticas en este primer estudio. Posteriormente, para facilitar la identificación de estas 8 especies filogenéticas en laboratorios de microbiología clínica, se estudiaron las características morfológicas macro- y microscópicas mas representativas de todas ellas así como su respuesta a 59 pruebas fisiológicas. Para incrementar la robustez de los diferentes clados, aumentamos el número de nuevos aislados y de éstos se secuenció la región TUB del gen de la β-tubulina, el cual previamente demostró ser el marcador molecular más informativo de los 4 evaluados. La combinación de estos estudios permitió distinguir fenotípicamente las mencionadas especies filogenéticas. La nueva especie Scedosporium dehoogii (previamente clado 3) fue descrita y Scedoporium apiospermum (previamente clado 4) y P. boydii fueron consideradas como dos especies diferentes. El nuevo nombre Scedosporium boydii fue propuesto para denominar al anamorfo de la última especie. Scedosporium dehoogii pudo ser separada del resto porque no crece a 40ºC y presenta conidioforos no ramificados. Aunque S. apiospermum fue morfológicamente indistinguible del anamorfo de P. boydii ambas especies pudieron ser separadas por su respuesta a las pruebas de la D-ribosa y por la presencia o ausencia de teleomorfo.
Durante la búsqueda de nuevos aislados utilizando el medio DRBC suplementado con benomilo, aislamos un hongo interesante de suelo de Argentina que presentaba una morfología similar a la de Scedosporium. Un estudio más detallado a nivel genético y morfológico nos permitió ver que este hongo era diferente a las especies conocidas de éste y otros géneros relacionados, por lo que propusimos el nuevo género Parascedosporium. Su carácter distintivo es el desarrollo simpodial de los conidios a partir de células conidiógenas denticuladas. Este aislado resultó ser morfológicamente idéntico a Graphium tectonae, por lo que propusimos la nueva combinación Parascedosporium tectonae. El análisis filogenético de las secuencias de 4 regiones de los 3 genes ya trabajados en el primer estudio confirmó nuestra propuesta.
En esta tesis también evaluamos la actividad in vitro de 11 antifúngicos (anfotericina B, albaconazol, fluconazol, itraconazol, ketoconazol, posaconazol, ravuconazol, voriconazol, terbinafina, micafungina y flucitosina) utilizando el método de microdilución del CLSI contra 84 aislados pertenecientes a las 8 especies que constituyen el complejo P. boydii. Encontramos diferencias significativas entre las especies, siendo Scedosporium aurantiacum la más resistente. En general, el voriconazol fue el antifúngico más activo, seguido del posaconazol.
Otro objetivo de la presente tesis fue comparar la virulencia de alguna de las diferentes especies del complejo utilizando un modelo murino con animales inmunocompetentes e inmunosuprimidos. Se seleccionaron 2 inóculos diferentes, 5x104 conidia/mL (para los animales inmunosuprimidos) y 1x106 conidia/mL (para los animales inmunocompetentes). S. aurantiacum y S. dehoogii fueron significativamente las especies más virulentas, causando la muerte del 80% y 70% de los ratones inmunocompetentes, respectivamente, mientras que el resto de las especies sólo consiguió entre un 0% y un 20% de mortalidad.
Finalmente, debido a que ninguna de las cepas estudiadas de la especie más común del complejo, S. apiospermum, había desarrollado la forma sexual, consideramos interesante determinar si se trataba de una especie heterotálica. Para ello, realizamos cruzamientos con 15 cepas de S. apiospermum en todas las combinaciones posibles, incluyendo cruzamientos consigo misma. Algunos cruzamientos entre distintas cepas produjeron ascomas fértiles, mientras que los cruzamientos con subcultivos de una misma cepa resultaron autoestériles. Las cepas pudieron separarse en dos diferentes "mating types". Corroboramos el bi-alelismo del sistema de cruzamiento heterotálico mediante cruzamientos entre las ascosporas de la progenie F1 de un cruzamiento positivo. Todos estos datos confirmaron que S. apiospermum es una especie heterotálica.
Pseudallescheria boydii is a ubiquitous ascomycetous fungus that causes a wide array of human infections that can affect practically all the organs of the body. These infections have been known for a long time, but in recent years, a marked increase in severe invasive infections has been noticed, mainly in immunocompromised hosts. They present a high mortality rate and are difficult to treat. One of the most typical features of this species, which is very rare in other pathogenic fungi, is its ability to develop sexual structures on routine culture media. Until the present thesis Scedosporium apiospermum was considered the anamorph of P. boydii.
Recently, it had been demonstrated that high genetic variation exists within P. boydii and other authors had reported considerable differences with respect to growth and sporulation. All these data seemed to suggest that P. boydii was probably a species complex. For this reason we performed a morphological and molecular study involving numerous strains of clinical and environmental origins and from different countries. The analysis of partial sequences of the β-tubulin (two loci) and calmodulin genes and the internal transcribed spacer region of the rDNA gene demonstrated that P. boydii is a species complex. A combined analysis of the sequences of the four loci of 60 strains from different origins showed 8 phylogenetic species within this species, grouped in 5 different clades. The clades 1 and 2 were described as the new species Scedosporium aurantiacum and Pseudallescheria minutispora, respectively. Clade 5 consisted of four subgroups incorporating the ex-type strains of P. boydii, Pseudallescheria angusta, Pseudallescheria ellipsoidea and Pseudallescheria fusoidea, respectively, and clades 3 and 4 remained unnamed. Later, in order to facilitate their identification in the clinical microbiology laboratories we tried to characterize phenotypically those 8 phylogenetic species. In order to increase the robustness of the different clades, we included in this study numerous fresh isolates identified by sequencing the TUB region of the β-tubulin gene, which previously was revealed as the most informative molecular marker of the four evaluated. The most representative macro- and microscopic morphological features of all them were studied and their responses to 59 physiological tests were evaluated. The combination of these studies allowed us to distinguish phenetically the mentioned phylogenetic species. The new species Scedosporium dehoogii (previously clade 3) was described and Scedoporium apiospermum (previously clade 3) and P. boydii were considered two different species The new name Scedosporium boydii was proposed for the anamorph of the latter species. Scedosporium dehoogii can be separated from the rest because it does not growth at 40ºC and present unbranched conidiophores. Although S. apiospermum were morphologically indistinguishable from the anamorph of Pseudallescheria boydii both species can be separated by the response to D-ribose test and by the presence or absence of a teleomorph.
During the study of fresh isolates recovered from different geographical areas we recovered an interesting Scedosporium-like fungus from Argentinean soil samples which was proven to be genetically and morphologically different from the known species of Scedosporium and relatives. Diverse morphological and molecular studies confirmed the uniqueness of such fungus and was proposed as the new genus Parascedosporium.. This genus is mainly characterized by producing sympodial conidia from denticulate conidiogenous cells. Further studies demonstrated that such isolate was identical to Graphium tectonae and thus the new combination Parascedosporium tectonae was proposed.
In this thesis we also evaluated the in vitro activities of 11 drugs (amphotericin B, albaconazole, fluconazole, itraconazole, ketoconazole, posaconazole, ravuconazole, voriconazole, terbinafine, micafungin and flucytosine) by using the microdilution method following the CLSI guidelines against 84 isolates belonging to the eight species that constitute the Pseudallescheria boydii complex. We found significant differences among the species, with Scedosporium aurantiacum being the most resistant. In general, voriconazole was the most active drug, showing a total geometric mean MIC of 0.61 g/ml, followed by posaconazole.
Another objective of the present thesis was to compare the virulence of the different species of the complex using a murine model of disseminated infection by these species. We used two different inocula, i.e., 5x104 conidia/ml and 1x106 conidia/ml, for each fungal strain tested. When mice were infected with the first inoculum animals were immunosuppressed while that those infected with the second inoculum were inmunocompetent. No significant differences in mortality rates were observed (p>0.05) among the species in the immunosupressed animals. In the case of inmunocompetent animals, S. aurantiacum and S. dehoogii were clearly the most virulent species of the complex both showed the highest mean mortality rate (80% and 70%, respectively, versus 0%-20% for the other species).
Finally, since none of the strains studied of the most common species of the complex, S. apiospermum, never developed the sexual state we considered of interest to determine if it was a heterothallic species. For this purpose, 15 strains of this species were paired in all possible combinations, including self-pairings to corroborate this hypothesis. All strains were self-sterile and several combinations of strains produced fertile ascomata. The strains could separate in two groups of different mating types. We corroborated the bi-allelic heterothallic mating system suggested by these results with crosses among F1 progeny ascospores from one positive mating test. All these data confirmed that S. apiospermum is a heterothallic species.

La SFIO des années 1960 est un parti politique sur le déclin. Son incapacité à répondre aux défis politiques du temps, son inadaptation à la Vème République et la volonté inaltérable de Guy Mollet de garder le contrôle sur l’organisation empêchent toute évolution profonde de la « vieille maison ». La conduite par la SFIO des négociations préparatoires à la création du NPS ne permet pas de sauver le parti aux yeux de l’opinion. La « vieille maison » disparaît le 4 mai 1969 lors du congrès d’Alfortville
The 1960s SFIO is a political party on the decline. Its inability to respond to the political challenges of the time, its unsuitability to the Fifth Republic and Guy Mollet's unalterable desire to maintain control over the organization prevent any profound evolution of the "vieille maison". The management by the SFIO of the preparatory negotiations for the creation of the NPS does not save the party in the opinion. The "vieille maison" disappears on May 4, 1969 at the Alfortville convention

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Formular modelos estatÃsticos voltados à realizaÃÃo de previsÃes no curto prazo (atà 12 passos à frente) sobre a arrecadaÃÃo do FGTS, com vistas a contribuir com a precisÃo das estimativas contidas em seu orÃamento anual à o objetivo da presente pesquisa. Os recursos do FGTS constituem um funding significativo para o governo federal financiar obras de habitaÃÃo, saneamento e infra-estrutura, geradoras de grande impacto econÃmico e social. A Caixa EconÃmica Federal à o agente operador do FGTS, pelo que tem a responsabilidade de administrar a arrecadaÃÃo de suas contribuiÃÃes, sob a supervisÃo do Conselho Curador do FGTS â CCFGTS e do MinistÃrio das Cidades, ÃrgÃo gestor das aplicaÃÃes e responsÃvel pela elaboraÃÃo do OrÃamento Anual. A cada final de ano sÃo feitas previsÃes sobre a arrecadaÃÃo do FGTS com vistas a subsidiar o planejamento orÃamentÃrio e financeiros de seus recursos. Tais previsÃes tem uma importÃncia crucial, na medida em que pequenas margens de erro podem gerar distorÃÃes expressivas, considerando o volume dos valores envolvidos em termos absolutos, situaÃÃo que exige um alto grau de precisÃo. Para anÃlise e modelagem das sÃries de arrecadaÃÃo do FGTS foram utilizados os modelos de alisamento exponencial e ARIMA, alÃm da tÃcnica de combinaÃÃo de previsÃes. Os resultados das previsÃes feitas a partir destes modelos foram melhores que as constante no orÃamento do FGTS, o que sugere a necessidade de revisÃo das tÃcnicas aplicadas no modelo atual.
To formulate statistical models directed to the accomplishment of forecasts in short term (up to 12 steps to the front) on the collection of the FGTS, with sights to contribute with the precision of the estimates contained in its annual budget is the objective of the present research. The resources of the FGTS constitute one significant funding it federal government to finance workmanships of habitation, sanitation and infrastructure, generating of great economic and social impact. Caixa EconÃmica Federal is the operator agent of the FGTS, for that it has the responsibility to manage the collection of its contributions, under the supervision of the Advice Custodian of the FGTS - CCFGTS and the Ministry of the Cities, managing agency of the applications and responsible for the elaboration of the Annual Budget. To each end of year forecasts on the collection of the FGTS with sights are made to subsidize the budgetary and financial planning of its resources. Such forecasts have a crucial importance, in the measure where small margins of error can generate expressives distortions, considering the volume of the involved values in absolute terms, situation that demands one high degree of precision. For analysis and modeling of the series of collection of the FGTS the models of exponential smoothing and ARIMA had been used, beyond the technique of combination of forecasts. The results of the done forecasts to leave of these models had been better that the constant in the budget of the FGTS, what it suggests the necessity of revision of the techniques applied in the current model.

Orientador: José Buratini Júnior
Banca: Paula de Carvalho Papa
Banca: João Carlos Pinheiro Ferreira
Resumo: A compreensão dos mecanismos moleculares controladores do desenvolvimento, função e regressão do CL bovino é necessária para o aprimoramento da manipulação hormonal ovariana. Fortes evidências sugerem o envolvimento de fatores de crescimento fibroblástico (FGFs) na regulação do crescimento e regressão do CL. "Splicing" alternativo de 4 genes formam sete subtipos de FGFRs com afinidade variável por diferentes FGFs. Os membros da subfamília do FGF8 (FGF8, 17 e 18) ativam eficientemente o FGFR3C e 4 e podem atuar em cooperação nos tecidos que expressão estes receptores. O objetivo deste trabalho foi determinar o padrão de expressão dos FGFRs e dos membros da subfamília do FGF8 no CL bovino (CL). Os CLs foram obtidos de ovários de abatedouro e classificados em 4 estádios de desenvolvimento (estádio/1= corpo hemorrágico, estádio/2= CL em desenvolvimento, estádio/3= CL maduro/início da luteólise funcional e estádio/4= luteólise estrutural). O RNAm foi mensurado por PCR semiquantitativo e a proteína localizada por imunohistoquímica. A expressão do RNAm codificante das isoformas 'B' e 'C' de FGFR1 e FGFR2 foi detectada no CL bovino por PCR associado à eletroforese e foi acompanhada pela localização da proteína nas pequenas e grandes células luteínicas. A expressão do RNAm do FGFR1C e 2C não variou durante o desenvolvimento luteínico, distintamente a expressão do FGFR1B aumentou no estádio 3. Embora os FGFRs 3B, 3C e 4 tenham sido detectados de forma inconsistente por PCR associado à eletroforese, o RNAm do FGFR3C e FGFR4 foram detectados por PCR em tempo real em todos os estádios do desenvolvimento luteínico. O RNAm do FGF18 foi detectado por PCR em tempo real em todos os estádios do desenvolvimento luteínico e sua abundancia do RNAm do FGF18 foi maior no estádio 3 comparado com os estádios 1, 2 e 4. Em contraste, os RNAm do FGF8 e 17 ... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: The molecular mechanisms controlling the development, function and regression of the bovine corpus luteum are necessary for the improvement of reproductive biotechnologies. Strong evidence suggests the involvement of fibroblast growth factors (FGFs) in the regulation of growth, and regression of the corpus luteum (CL). Alternative splicing of 4 genes give rise to seven subtypes of FGFRs with varying affinity for different FGFs. FGF8 subfamily members (FGF8, 17 and 18) efficiently activate FGFR3C and FGFR4 and may act in cooperation in tissues expressing these receptors. The objective of the present study was to determine the pattern of expression of FGF8 subfamily members and FGFRs in the bovine CL. Bovine CLs were obtained from abattoir ovaries and classed into four stages of development (stage 1= corpus hemorragicum, stage 2= developing CL, stage 3= mature/early functional luteolysis CL, and stage 4= structural luteolysis). Expression of mRNA was measured by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) followed by gel analysis (FGFR1-4) and real time RT-PCR (FGF8 subfamily members, FGFR3C and FGFR4) and proteins were localized by immunohistochemistry. Expression of mRNA encoding 'B' and 'C' spliced forms of FGFR1 and FGFR2 was readily detected in the bovine CL and was accompanied by isoform non-specific protein localization. FGFR1C and FGFR2C mRNA expression did not vary throughout CL lifespan, whereas FGFR1B was upregulated in the mature CL (stage III). FGFR3B, FGFR3C and FGFR4 expression was inconsistent in the bovine CL as assessed by PCR associated with gel analysis. FGF18, FGFR3C and FGFR4 mRNA was detected by real time PCR in all four developmental stages, and FGF18 mRNA abundance was higher in stage 3 (2.89  0.05; mean ± SEM) compared with stages 1 (0.3  0.27), 2 (0.56  1.27) and 4 (0.99  0.32). The m RNA expression ... (Complete abstract click electronic access below)
Mestre

Le cancer de la prostate est le cancer le plus fréquemment diagnostiqué et la deuxième cause de mortalité par cancer chez l'homme dans les pays occidentaux. Son développement est souvent très lent et les premiers signes cliniques n'apparaissent généralement pas avant 60 ans. Néanmoins, l'adénocarcinome prostatique représente un important problème de santé publique et de ce fait, d'importants efforts ont été entrepris au niveau de la recherche depuis une dizaine d'années. La prostate est constituée de deux compartiments distincts : le stroma et le compartiment glandulaire. Les relations autocrines/paracrines existant entre ces deux compartiments sont à la base de la physiologie de la prostate normale mais également de l'établissement et de la progression du cancer de la prostate. Ces relations sont réalisées par l'intermédiaire de peptides ou facteurs de croissance produits en majorité par les fibroblastes et dont certains sont sous le contrôle des androgènes. La famille des facteurs de croissance fibroblastiques (fibroblast growth factors, FGFs) semble jouer un rôle fondamental à la fois dans l'homéostasie prostatique et dans l'initiation et la progression du cancer de la prostate. Au cours de ce travail, nous avons plus particulièrement étudié deux d'entre eux : le FGF2 (bFGF) et le FGF7 (KGF). Nous avons caractérisé trois lignées de cellules épithéliales prostatiques humaines immortalisées par SV40 et transfectées par ces facteurs de croissance fibroblastiques : PNT1A/FGF2, PNT1A/FGF7 et PNT2/FGF7. Nos résultats font apparaître qu'une boucle de stimulation autocrine à la fois de FGF2 et de FGF7 donne aux cellules un phénotype " transformé " c'est-à-dire que les cellules sont capables de pousser dans un milieu semi-solide, dans un milieu sans sérum et que leur vitesse de prolifération est sensiblement augmentée. En plus des propriétés caractéristiques du phénotype " transformé ", les cellules transfectées par FGF7 peuvent traverser une membrane basale reconstituée (Matrigel) démontrant leur potentiel invasif, à la différence des cellules transfectées par FGF2. En conclusion, nous pouvons dire qu'une expression constitutive du FGF2 ou du FGF7 amenant à l'établissement d'une boucle de stimulation autocrine sur les cellules épithéliales prostatiques humaines induit une transformation cellulaire ainsi qu'une indépendance des cellules épithéliales par rapport aux facteurs de croissance (croissance dans un milieu sans sérum). In vivo, la constitution d'une telle boucle autocrine rendrait les cellules épithéliales indépendantes du stroma et pourrait être l'une des hypothèses de l'initiation de l'androgéno-indépendance du cancer de la prostate, synonyme de mauvais pronostic.

Propagation of cracks in functionally graded materials (FGMs) under cyclic loading was investigated via experiments and finite element (FE) analysis. Alumina-epoxy composites with an interpenetrating-network structure and tailored spatial variation in composition were produced via a multi-step infiltration technique. Compressed polyurethane foam was infiltrated with alumina slip. After foam burn-out and sintering, epoxy was infiltrated into the porous alumina body. Non-graded specimens with a range of compositions were produced, and elastic properties and fatigue behaviour were characterised. An increase in crack propagation resistance under cyclic loading was quantified via a novel analytical approach. A simulation platform was developed with the commercial FE package ANSYS. Material gradient was applied via nodal temperature definitions. Stress intensity factors were calculated from nodal displacements near the crack-tip. Deflection criteria were compared and the local symmetry criterion provided the most accurate and efficient predictions. An automated mesh-redefinition algorithm enabled incremental simulation of crack propagation. Effects of gradient and crack-geometry parameters on crack-tip stresses were investigated, along with influences of crack-shape, crack-bridging, residual stresses and plasticity. The model provided predictions and data analysis for experimental specimens. Fatigue cracks in graded specimens deflected due to elastic property mismatch, concordant with FE predictions. In other FGMs, thermal or plastic properties may dominate deflection behaviour. Weaker step-interfaces influenced crack paths in some specimens; otherwise effects of toughness variation and gradient steps on crack path were negligible. Crack shape has an influence, but this is secondary to that of elastic gradient. Cracks in FGM specimens initially experienced increase in fatigue resistance with crack-extension followed by sudden decreases at step-interfaces. Bridging had a notable effect on crack propagation resistance but not on crack path. Similarly, crack paths did not differ between monotonic and cyclic loading, although crack-extension effects did. Recommendations for analysis and optimisation strategies for other FGM systems are given. Experimental characterization of FGMs is important, rather than relying on theoretical models. Opportunities for optimization of graded structures are limited by the properties of the constituent materials and resultant general crack deflection behaviour.

Tese (doutorado)—Universidade de Brasília, Faculdade de Direito, Programa de Pós-Graduação em Direito, 2015.
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Esta tese discute se e como um modelo de constituição de reservas pessoais poderia, do ponto de vista constitucional, ser instituído no Brasil para financiamento de benefícios previdenciários. O texto propõe um modelo teórico, chamado de Fundo de Garantia da Previdência Social – FGPS, que seria uma opção livre para pessoas inseridas no Regime Geral da Previdência social. O trabalho investigou a literatura jurídica e a jurisprudência para identificar que condicionamentos devem ser observados para que tal modelo teórico seja compatível com a ordem constitucional brasileira. Esta investigação resultou na identificação de três diretrizes gerais: preservação de direitos, garantia de mínimo de proteção securitária e manutenção da solidariedade do sistema. O trabalho propôs então a utilização da Teoria de Justiça de Rawls para consolidar estas diretrizes gerais em exigências normativas específicas. Do ponto de vista dos direitos do segurado individual, essas exigências impõem (1) regras prudenciais que promovam a formação de poupança e (2) garantias estatais de cobertura de benefícios mínimos em caso de poupança insuficiente. Do ponto de vista dos direitos da coletividade de segurados, as diretrizes são atendidas ao se condicionar a opção pelo FGPS a (1) ganho financeiro para o sistema previdenciário como um todo e (2) disponibilidade de fluxo de caixa pelo sistema para pagamento de benefícios no curto prazo. A contribuição que esta tese pretende fazer ao conhecimento sobre a matéria envolve (1) a definição das diretrizes para reforma e (2) a identificação de como contas pessoais podem atender a estas diretrizes e ser implementadas dentro da ordem constitucional brasileira.
This thesis addresses, from a Constitutional Law point of view, whether and how a model based on personal savings could be adopted in Brazil to finance social security benefits. A hypothetical Social Security Fund – SSF is described as an option available for those currently in Brazil’s General Social Security Regime. The author investigated both academic legal publications and judicial discussions in order to describe which conditions should be met so the SSF may pass a constitutionality test in Brazil. This investigation resulted in the finding of three general guidelines: preserving rights, assuring minimum benefits and preserving solidarity within the system. Rawls’ Theory of Justice was then used to consolidate these guidelines into specific normative demands. From the point of view of the rights of each individual, these demands are met by (1) prudential regulation that fosters savings and (2) government guarantees in case savings are insufficient to fund benefits. From the point of view of the rights of the collectivity of people subject to the General Regime, the demands are met if the SSF option is conditioned to (1) financial gain for the social security system as a whole and (2) availability of sufficient cash to pay for benefits for other beneficiaries in the short term. The contribution to current knowledge this thesis intends to offer is (1) defining guidelines for social security reform and (2) verifying how personal accounts can meet these guidelines and be implemented according to Brazilian constitutional law.

O estudo trata da análise da gestão, pelo Estado, das políticas sociais nas áreas do trabalho e da assistência social, tendo como referência a FGTAS e as transformações ocorridas em seu processo histórico, com o propósito de conhecer as repercussões da redefinição do papel do Estado na área social para essa estrutura, enfatizando-se as mudanças ocorridas em função da Reforma de Estado que vem sendo implementada desde o início dos anos 90. O trabalho realizou-se através de uma pesquisa qualitativa, optando-se por uma abordagem dialético- -crítica, configurando-se como um estudo de caso histórico-organizacional da FGTAS. Foram adotadas como técnicas, a pesquisa documental e a análise de conteúdo, criando-se, para tanto, categorias, a partir das quais foram trabalhados os resultados obtidos através das entrevistas com os agentes executores das políticas sociais, que objetivaram traduzir a visão deles sobre os eixos temáticos abordados neste trabalho. Tais resultados demonstraram que, em muitos momentos das entrevistas, as falas dos agentes e dos gestores não foram contraditórias, tendo em vista terem apresentado similitude em seus argumentos e em suas idéias sobre os assuntos tratados. Evidenciou-se, através deste estudo, a fragilidade quanto à concepção das políticas sociais, em particular na área da assistência social. Demonstrou-se, ainda, o processo histórico de desmontagem das estruturas de atendimento à área social pelo setor público estadual gaúcho em razão das sucessivas “reformas administrativas” nessa área, o que tem levado esse setor a não responder às demandas sociais. A fragilidade da identidade institucional da FGTAS ficou evidente. Em função desse conjunto de questões, sugere-se a ampliação dos custos sociais, com a redefinição do papel do Estado nesse setor, o que se caracterizou como a crise na área social. Constatou-se, também, a existência de uma crise de gestão do Estado nessa área, confirmada, em particular, pela própria fala dos gestores, tendo a descontinuidade político-administrativa como um marco característico, em razão da rotatividade de gestores e da ausência de visibilidade de ações concretas no sentido de se contrapor às dificuldades identificadas. A profissionalização da gestão pública foi sugerida dentre outras mudanças, bem como a adoção de algumas das idéias âncoras oferecidas pelas modernas tendências das teorias administrativas, com a intenção de imprimir um novo perfil de gestão pública, capaz de apresentar as condições necessárias para acompanhar as grandes transformações que se fazem presentes na virada do século.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2006.
Vita.
Includes bibliographical references.
Purine biosynthesis has been used as a paradigm for the study of metabolism of unstable molecules. Both phosphoribosylamine (PRA) and N5-carboxyaminoimidazole ribonucleotide (N5-CAIR) have estimated half-lives in vivo of seconds. In order to avoid metabolite decomposition, one strategy cells could employ is channeling-the direct transfer of a metabolite between enzyme active sites without diffusion into the bulk media. While kinetic evidence for channeling of PRA has been reported between phosphoribosylpyrophosphate amidotransferase (PurF) and glycinamide ribonucleotide synthetase (PurD), no evidence for a PurF:PurD complex has been found. In an effort to detect this complex, stopped-flow fluorescence spectroscopy was used to detect changes in PurF fluorescence that may result from interaction with PurD. Critical to the success of these experiments was incorporation of tryptophan analogs (4-fluorotryptophan and 7-azatryptophan) into the proteins in order to increase signal specificity for PurF. No evidence for a PurF:PurD interaction was found under any of the conditions tested. The implication of this finding is discussed with regard to the PurF:PurD channeling model. Like all amidotransferase enzymes (ATs), channeling of NH3 between glutaminase and AT active sites has been implicated in the formylglycinamide ribonucleotide amidotransferase (FGAR-AT).
(cont.) In B. subtilis, the FGAR-AT is composed of three proteins: PurS, PurQ, and small PurL. The first characterization of the B. subtilis FGAR-AT complex was carried out, and it was determined that a complex between the three proteins can only be isolated in the presence of Mg2+-ADP and glutamine. By analogy to the Salmonella FGAR-AT, ADP is believed to be acting as a structural cofactor, while formation of a PurQ-glutamine complex is essential for assembly of the FGAR-AT. Subsequent biophysical studies have indicated that the physiologically relevant form of the FGAR-AT complex contains 2 PurS, 1 PurQ, and 1 small PurL. Further studies on PurQ have identified residues important for catalysis and complex formation, while insight into the small PurL active site has been obtained by studies on the T. maritima enzyme. The FGAR-AT complex provides a new system in purine biosynthesis to study metabolite transfer among weakly interacting proteins.
by Aaron A. Hoskins.
Ph.D.

O presente trabalho de pesquisa tem como proposta identificar os pontos críticos e apresentar reflexões sobre o modelo jurídico de recuperação dos créditos do Fundo de Garantia do Tempo de Serviço - FGTS em face dos empregadores, tanto no âmbito da cobrança judicial envidada pelos trabalhadores, quanto no plano das cobranças administrativa e judicial promovidas pela União, considerando os interesses sociais envolvidos e as finalidades perseguidas pelos agentes da recuperação, e tendo como paradigma a compreensão do FGTS como direito fundamental do trabalhador, a exigir efetividade do modelo de recuperação dos seus créditos.
This research aims to reflect upon and identify the difficulties connected with the recovery of debts owed to the Brazilians Employment Compensation Fund, in Portuguese Fundo de Garantia do Tempo de Serviço (FGTS). The focus is both in the workers lawsuits against employers, as well as the administrative and judicial measures taken by the Federal Government through their attorneys. The recovery of the debts owed to the Fund is analyzed within the frame of workers fundamental rights guaranteed by the Constitution, demanding effectiveness.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Durante o desenvolvimento ovariano fetal, a formação folicular inicial é decisiva para a fertilidade da fêmea, pois define sua reserva gametogênica. Tem sido proposto que a progesterona e o estradiol desempenham papel regulatório na foliculogênese pré-antral, de forma que sua produção reduzida em ovários fetais bovinos antecede o surgimento de folículos primordiais e primários. Recentemente, os FGFs 10 e 18 foram reportados em folículos ovarianos bovinos como redutores dos níveis de esteróides, o que parece envolver a inibição da expressão de enzimas necessárias à esteroidogênese. Em adição, a expressão do FGF10 foi observada durante o desenvolvimento ovariano fetal bovino, e esteve positivamente associada ao aumento no número de folículos primários. O presente estudo investigou primeiramente o padrão de expressão do RNAm das enzimas esteroidogênicas (StAR, CYP11A1, 3β-HSD, CYP17A1, CYP19A1 e 17β-HSD) em ovários de fetos bovinos em idades gestacionais específicas (60, 75, 90, 120, 150 e 210 dias). Todos os genes investigados se mostraram expressos e regulados ao longo da gestação. Os níveis de RNAm da CYP19A1 diminuíram dos 60 para os 90 dias, sugerindo envolvimento desta enzima com a produção decrescente de estradiol observada previamente durante este período gestacional. A expressão das demais enzimas foi elevada ao longo da gestação, coincidente com o aumento da competência esteroidogênica descrito preliminarmente durante o desenvolvimento folicular inicial. Em adição, foi investigada a participação dos FGFs 10 e 18 na esteroidogênese ovariana fetal bovina. A expressão do FGF18 e de seus receptores (FGFR2C, FGFR3C e FGFR4) foi detectada em ovários fetais bovinos ao longo da gestação (60, 75, 90, 120, 150 e 210 dias). A abundância de RNAm do FGF18 aumentou...
During fetal ovarian development, early follicular formation is essential to female fertility, when the gametogenic reserve is defined. It has been proposed that progesterone and estradiol play regulatory role on preantral folliculogenesis, once its reduced production in bovine fetal ovaries precedes primordial and primary follicle assembly. Recentlly, FGFs 10 and 18 were reported in bovine ovarian follicles as reducers of steroids levels, and this seems to involve the inhibition of enzymes necessary to steroidogenesis. In addition, FGF10 expression was observed during bovine fetal ovary development, and it was positively associated with the elevation on primary follicles number. The present study first investigated the mRNA expression patterns for steroidogenic enzymes (StAR, CYP11A1, HSD3B1, CYP17A1, CYP19A1 and HSD17B1) in bovine fetal ovaries at specific gestational ages (60, 75, 90, 120, 150 e 210 days). Expression of all investigated genes was detected and regulated through gestation. Messenger RNA levels of CYP19A1 decreased from days 60 to 90 of gestation, suggesting involvement of this enzyme on decrescent estradiol production previously observed during this gestational period. The expression of other enzymes was elevated during gestational period, which was coincident with the enhance of steroidogenic competence previously described during early follicular development. In addition, the participation of FGFs 10 and 18 on steroidogenesis in bovine fetal ovaries was investigated. The expression of FGF18 and its receptors (FGFR2C, FGFR3C and FGFR4) was detected in bovine fetal ovaries through gestation (60, 75, 90, 120, 150 e 210 days). The mRNA abundance of FGF18 enhanced between 90 and 120 days and decreased at 210 days. The expression of FGFR2C and FGFR4 did not vary during... (Complete abstract click electronic access below)

Orientador: José Buratini Junior
Banca: José Antonio Visitin
Banca: Guilherme de Paula Nogueira
Banca: Fernanda da Cruz Landim e Alvarenga
Banca: Sony Dimas Bicudo
Resumo: Durante o desenvolvimento ovariano fetal, a formação folicular inicial é decisiva para a fertilidade da fêmea, pois define sua reserva gametogênica. Tem sido proposto que a progesterona e o estradiol desempenham papel regulatório na foliculogênese pré-antral, de forma que sua produção reduzida em ovários fetais bovinos antecede o surgimento de folículos primordiais e primários. Recentemente, os FGFs 10 e 18 foram reportados em folículos ovarianos bovinos como redutores dos níveis de esteróides, o que parece envolver a inibição da expressão de enzimas necessárias à esteroidogênese. Em adição, a expressão do FGF10 foi observada durante o desenvolvimento ovariano fetal bovino, e esteve positivamente associada ao aumento no número de folículos primários. O presente estudo investigou primeiramente o padrão de expressão do RNAm das enzimas esteroidogênicas (StAR, CYP11A1, 3β-HSD, CYP17A1, CYP19A1 e 17β-HSD) em ovários de fetos bovinos em idades gestacionais específicas (60, 75, 90, 120, 150 e 210 dias). Todos os genes investigados se mostraram expressos e regulados ao longo da gestação. Os níveis de RNAm da CYP19A1 diminuíram dos 60 para os 90 dias, sugerindo envolvimento desta enzima com a produção decrescente de estradiol observada previamente durante este período gestacional. A expressão das demais enzimas foi elevada ao longo da gestação, coincidente com o aumento da competência esteroidogênica descrito preliminarmente durante o desenvolvimento folicular inicial. Em adição, foi investigada a participação dos FGFs 10 e 18 na esteroidogênese ovariana fetal bovina. A expressão do FGF18 e de seus receptores (FGFR2C, FGFR3C e FGFR4) foi detectada em ovários fetais bovinos ao longo da gestação (60, 75, 90, 120, 150 e 210 dias). A abundância de RNAm do FGF18 aumentou... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: During fetal ovarian development, early follicular formation is essential to female fertility, when the gametogenic reserve is defined. It has been proposed that progesterone and estradiol play regulatory role on preantral folliculogenesis, once its reduced production in bovine fetal ovaries precedes primordial and primary follicle assembly. Recentlly, FGFs 10 and 18 were reported in bovine ovarian follicles as reducers of steroids levels, and this seems to involve the inhibition of enzymes necessary to steroidogenesis. In addition, FGF10 expression was observed during bovine fetal ovary development, and it was positively associated with the elevation on primary follicles number. The present study first investigated the mRNA expression patterns for steroidogenic enzymes (StAR, CYP11A1, HSD3B1, CYP17A1, CYP19A1 and HSD17B1) in bovine fetal ovaries at specific gestational ages (60, 75, 90, 120, 150 e 210 days). Expression of all investigated genes was detected and regulated through gestation. Messenger RNA levels of CYP19A1 decreased from days 60 to 90 of gestation, suggesting involvement of this enzyme on decrescent estradiol production previously observed during this gestational period. The expression of other enzymes was elevated during gestational period, which was coincident with the enhance of steroidogenic competence previously described during early follicular development. In addition, the participation of FGFs 10 and 18 on steroidogenesis in bovine fetal ovaries was investigated. The expression of FGF18 and its receptors (FGFR2C, FGFR3C and FGFR4) was detected in bovine fetal ovaries through gestation (60, 75, 90, 120, 150 e 210 days). The mRNA abundance of FGF18 enhanced between 90 and 120 days and decreased at 210 days. The expression of FGFR2C and FGFR4 did not vary during... (Complete abstract click electronic access below)
Doutor

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The main goal of the current academic work is to show and discuss the limits of the Housing Finance System (SFH) and Real Estate Financing System (SFI), with special focus on the analysis of housing funding limits. In this study the literature review was used as a source of empirical data. the statistics released by the Brazilian Association of Real Estate Credit and Savings Entities (ABECIP). The brazilian imobiliary funding issue goes through the long-term problem due to scarce credit lines. The capital market still falls far from the growing financing needs of the economy, especially with regard to corporate bonds. The funding sources that support the current housing credit volume are based on the Brazilian System of Savings and Loans (SBPE) and the Guarantee Fund for Employees (FGTS). It follows that the obstacle to increase the share of housing loans in GDP is not easy to solve. However, this work points clearly that the FGTS has the potential to offer lower financing rates than it has been offering. And it is also shown that SBPE is able to better allocate the funds raised by the savings
O objetivo principal deste trabalho é apontar e discutir os limites do Sistema Financeiro da Habitação (SFH) e do Sistema Financeiro Imobiliário (SFI), com especial destaque para a análise dos limites do funding habitacional. Neste trabalho foi adotada a pesquisa bibliográfica e usada como fonte de dados empíricos as estatísticas disponibilizadas pela Associação Brasileira das Entidades de Crédito Imobiliário e Poupança (ABECIP). A questão do funding imobiliário no Brasil é uma questão que passa pelo problema de funding de longo prazo, pois são escassas as linhas de crédito de longo prazo. O mercado de capitais, principalmente, no tocante a títulos corporativos, ainda está muito aquém das necessidades crescentes de financiamento da economia. As fontes de funding que sustentam o atual volume de crédito habitacional são pautadas no Sistema Brasileiro de Poupança e Empréstimo (SBPE) e no Fundo de Garantia por Tempo de Serviço (FGTS). Conclui-se que o entrave para aumentar da participação do crédito habitacional no PIB não é de fácil solução. Porém, fica claro que o FGTS tem potencial para oferecer taxas de financiamento mais baixas do que vem oferecendo e o SBPE tem condições de alocar melhor os recursos captados pela caderneta de poupança

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This end of course paper has the objective to analise the decision of Supreme Federal Court of Brasil whom judged unconstitutional the norm which provides trinary for the judicial collection of deposits not done from FGTS (Employment Time Guarantee Fund). It treats from a decision that generated a lot of criticism as, many workers felt impaired with the new point of Supreme Court. In the begining, will be analysing the concept of presciption in labor law, the influence in interpretation of norms and the definition of protector principle. Then, it will be study the concept of legal nature of FGTS. It will be observed the prescription of the FGTS in the law 8.036/90, the prescription of labor credits in the CF/88(Federal Constitution of Brazil) and the possibility of conflits among constitutional norm about prompt prescription and the principle most favourable norm. The study will be carried out through empirical, bibliographic, qualitative, exploratory, descriptive and documentary research. The methodology to be adopted will be critical analysis of legal discourse through which the decision pronounced by the STF is investigated in an attempt to understand the change of a jurisprudential understanding consolidated for years. Finaly, we hope to identify the consequences of the aplicability from the new prescriptional promt could bring to the legal effectiveness about the worker´s rights.
O trabalho tem como objetivo analisar a decisão do Supremo Tribunal Federal que julgou inconstitucional a norma que prevê a prescrição trintenária para a cobrança judicial dos depósitos não efetuados do FGTS. Trata-se de uma decisão que gerou críticas já que muitos trabalhadores se sentiram prejudicados com o novo posicionamento da Suprema Corte. De início, serão analisados os conceitos de prescrição no direito do trabalho, a influência na interpretação das normas e a definição do princípio protetor. Em seguida, serão estudados o conceito e a natureza jurídica do FGTS. Será observada a prescrição do FGTS na lei 8.036/90, a prescrição dos créditos trabalhistas na CF/88 e o possível conflito existente entre a norma constitucional sobre o prazo prescricional e o princípio da norma mais favorável. O estudo será realizado por meio de pesquisas empírica, bibliográfica, qualitativa, exploratória, descritiva e documental. A metodologia a ser adotada será a Análise Crítica do Discurso Jurídico por meio da qual se investiga a decisão proferida pelo STF na tentativa de entender a mudança de um entendimento jurisprudencial consolidado há anos. Como resultado, espera-se identificar as consequências que a aplicabilidade do novo prazo prescricional possa vir a trazer tanto à eficácia da justiça, quanto aos direitos dos trabalhadores.

En un mundo donde el mercado de trabajo es cada vez más competitivo, el desarrollo de competencias y de las prácticas pre profesionales se vuelve factores críticos para la inserción laboral. En este contexto, aparecen ciertos actores que facilitan el desarrollo de las competencias: la universidad, el centro laboral y el equipo de trabajo. Estos actores, a su vez, habilitan o no las condiciones para que se desarrollen estas competencias a través de condiciones sistemáticas, organizativas y participativas, respectivamente. La presente investigación tiene por objetivo la identificación de las condiciones que tienen mayor influencia, o facilitan de mejor manera, en el desarrollo de las competencias profesionales esperadas de un estudiante de Gestión Empresarial, a fin de identificar oportunidades de mejora y gestionar las mismas para facilitar su desarrollo. Para el presente estudio se hizo uso de un enfoque cualitativo sobre una muestra de treinta (30) entrevistas semi-estructuradas, las cuales se sistematizaron mediante el uso del análisis de frecuencias (patrones dominantes) y el análisis de contenido (importancia-principales razones). El estudio ha permitido identificar que la gestión de las condiciones sistemática, organizativa y participativa son claves para el desarrollo competencias de los estudiantes que cursan los últimos semestres. Sobre la condición sistemática, la cual se refiere a los aspectos curriculares (cursos) y metodológicos que la Facultad brinda al estudiante, se identificaron un grupo de cursos en los que los entrevistados desarrollan más las competencias que en otros. En relación, a lo organizativo, lo cual se refiere a los mecanismos que la empresa ofrece al practicante para su desarrollo, se observó que un mejor convenio de prácticas y mayor seguimiento ayudarían a desarrollar mejor las competencias en esta condición en el centro laboral. Por último, en relación a la condición participativa, la cual alude específicamente a los actores involucrados en el desempeño de las prácticas como el jefe directo y el equipo de trabajo, se pudo observar que la Facultad puede identificar e incentivar los centros laborales que desarrollen mejor las competencias. Así, se asegura una adecuada gestión de competencias donde se beneficien los actores involucrados: la empresa, el centro formativo educacional y, sobre todo, el practicante. De esta manera, un enfoque de formación por competencias debería incorporar la gestión de un grupo de condiciones tanto en la etapa formativa como en proceso de realización de las prácticas pre profesionales, las cuales son un requisito para el egreso y la obtención de grado y título de la Facultad de Gestión y Alta Dirección [FGAD].
Tesis

Les « fibroblast growth factors » acide et basique (FGFa et FGFb) sont des facteurs de croissance présents en quantités importantes dans le cerveau, mais dont la fonction dans cet organe reste inconnue. La prolifération cellulaire, évaluée par mesure de l'incorporation de 3H-thymidine, diminue au cours du développement du cerveau et particulièrement entre E7 et E10 puis à la naissance. La différenciation neuronale, évaluée par mesure des taux de neurotransmetteurs aminergiques, augmente au cours du développement et notamment entre E10 et E15. Les quantités de FGFa et b, déterminées par mesures de l'activité biologique et dosages immunologiques augmentent de façon importante entre E10 et E15. L'utilisation de techniques de dosage radiorécepteur et de pontage moléculaire révèle que le FGFa et FGFb interagissent au niveau de sites de fixation communs sur les membranes de cerveau. Deux catégories de sites de fixation spécifiques des FGFs ont été détectées : les sites de fixation à haute affinité et les sites de fixation à basse affinité. Les sites de fixation à haute affinité correspondent à des récepteurs de poids moléculaires apparents proches de 130 et 95 kDa. La capacité membranaire de ces récepteurs diminue au cours du développement du cerveau et particulièrement entre E7 et E10 puis entre P1 et l'état adulte
Cette diminution du nombre de récepteurs est similaire à la diminution de la quantité d'ARNm correspondant au gène BEK. Les sites de fixation à basse affinité sont généralement considérés comme étant des glycosaminoglycannes. L'extraction des glycosaminoglycannes du cerveau (E15) a permis de montrer que seuls les héparane sulfates fixent les FGFs, leur poids moléculaire est proche de 15 et 65 kDa et leur interaction avec le FGFb est définie par un Kd de 5 nM. Ces héparanes sulfates empêchent la fixation du FGFb sur les membranes de cerveau et inhibent l'activité mitogène de ce facteur de croissance. Une étude radioautographique montre que les héparanes sulfates fixant le FGFb sont localisés au niveau de l’ensemble du cerveau et particulièrement dans les éléments vasculaires. L’ensemble de ces résultats permet d’aborder l’activité biologique des FGFs au cours du développement du cerveau, qui semble régulée par l’expression de sites de fixation à haute et à basse affinité pour ces facteurs de croissance

Piptadenia stipulacea belongs to the Fabaceae family,and is widely distributed in the caatinga. This species is commonly known in the Brazilian Northeast as jurema-branca , carcará and rasga-beiço , and is used in folk medicine in inflammation.In this study, we attempted to identify the possible antinociceptive and anti-inflammatory activities of the aqueous phase, the ethyl acetate phase and one flavonoid obtained from aerial parts of Piptadenia stipulacea. Aerial parts of Piptadenia stipulaceawere used and after fractionation, the flavonoid Galetin 3,6-dimethyl ether(FGAL) was obtained of the chloroformic phase of this plant. Experiments were conducted on Swiss mice using the acetic acid-induced writhing test, the hot plate test, the formalin test and zymosan A-induced peritonitis test. To characterize the mechanism(s) responsible for these antinociceptive and anti-inflammatory actions of FGAL, COX inhibitor screening assay kit and test of DPPH was used. The aqueous and ethyl acetate phases (100 mg/kg, p.o.); and the flavonoid FGAL (100 μmol/kg, p.o. or i.p.), reduced the nociception produced by acetic acid, by 49,9 ± 11,2, 54,6 ± 5,3, 39,0 ± 6,8 and64,8% ± 8,1, respectively. As FGAL have greater antinociceptive activity when administered intraperitoneally compared to oral route, we chose this route you follow up the study with FGAL. The ethyl acetate phase (100 mg/kg, p.o.) reduced nociception in the hot plate, indicating that this fraction exhibited central activity. The ethyl acetate phase (100 mg/kg, p.o.) reduced the formalin effects in both phases by 40,2± 10,3 and59,9% ± 6,5, respectively. Treatment with the aqueous phase (100 mg/kg, p.o.) and FGAL (100_mol/kg, i.p.) only protected the second phase by 78,5± 5,5 and 64,0% ± 8,0, respectively. In addition, it was observed in the zymosan A-induced peritonitis test that the aqueous phase, the ethyl acetate phase and FGAL exhibited anti-inflammatory activity, reducing significantly the number of recruit cells by 35,8 ± 4,9, 37,7 ± 6,2 and 31,3% ± 13,3, respectively. Moreover, FGAL at 0,2μM was able to inhibit COX-1 (79,5% ± 0,6) and COX-2 (56,0% ± 3,8), with an inhibition profile similar to indomethacin in the same concentration (93.0 ±2.6and79.0±1.5%, respectively), showinginhibitionofCOX-1 in greaterproportionthanCOX-2. Furthermore, indomethacin was more effective, both COX-1 andCOX-2 when compared to FGAL. In the test of DPPH, FGAL showed high radical scavenging activity. These results infer that the aqueous phase, the ethyl acetate phase and FGAL obtained from aerial parts of Piptadeniastipulacea are able to modulate the peripheral nociception and acute inflammatory response. TheflavonoidFGALinhibitCOX-1 andCOX-2, probably for its ability to scavenge free radicals, this being one of its mechanism of action in nociception and inflammation. Moreover, the results corroborate the popular use of Piptadenia stipulacea by their anti-inflammatory property.
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
Piptadenia stipulacea,pertence à família Fabaceae, é amplamente distribuída na caatinga. Esta espécie é conhecida no Nordeste brasileiro como jurema-branca, carcará e rasga-beiço, sendo utilizada na medicina popular para tratar inflamação. Neste trabalho, buscou-se investigar a atividade antinociceptiva e anti-inflamatória da fase aquosa, fase acetato de etila e de um flavonoide isolado das partes aéreas de Piptadenia stipulacea. As partes aéreas de Piptadenia stipulacea foram usadas para o fracionamento e, posteriormente o flavonóide galetina 3,6-dimetil éter(FGAL)foi obtido da fase clorofórmica da planta. Experimentos foram realizados em camundongos Swiss usando o modelo de contorções abdominais induzidas por ácido acético, ensaio da placa quente, teste de formalina e peritonite induzida por zymosan A. Para caracterizar o mecanismo de ação de FGAL responsável por sua ação antinociceptiva, o ensaio de inibição de cicloxigenase (COX) in vitro e a análise da atividade sequestrante radicalar através do método fotocolorimétrico de consumo de 2,2-difenil-1-picrihidrazila(DPPH) foram utilizados. As fases aquosa e acetato de etila(100 mg/kg, v.o.); e o flavonoide FGAL (100 μmol/kg, v.o. ou i.p.) reduziram a nocicepção produzida por ácido acético, na proporção de 49,9 ± 11,2, 54,6 ± 5,3, 39,0 ± 6,8 e 64,8% ± 8,1, respectivamente.Por FGAL apresentar maior atividade antinociceptiva ao ser administrado pela via intraperitoneal quando comparado com a via oral, escolheu-se essa via para dar sequência ao estudo com FGAL. Posteriormente, verificou-se também a inibição da nocicepção no ensaio de placa quente através do tratamento com a fase acetato de etila (v.o., 100 mg/kg), indicando que esta fase apresenta atividade central. A fase acetato de etila (v.o., 100 mg/kg) reduziu a nocicepção gerada pela aplicação de formalina em ambas as fases do teste, apresentando porcentagem de inibição de 40,2 ± 10,3e 59,9% ± 6,5, respectivamente. O tratamento com a fase aquosa (100 mg/kg, v.o.) e FGAL (100 μmol/kg, i.p.) apenas se mostraram ativos na segunda fase do teste de formalina na proporção de 72,6± 5,5 e 66,0% ± 8,0, respectivamente. Além disso, as fases aquosa (100 mg/kg, v.o.), acetato deetila (100 mg/kg, v.o.) e FGAL (100 μmol/kg, i.p.) tambémapresentaram efeito anti-inflamatório significante quando comparadas ao grupo controle, apresentando porcentagem de inibição de recrutamento celular na peritonite induzida por zymosan A de 35,8 ± 4,9, 37,7 ± 6,2 e 31,3% ± 13,3, respectivamente.FGAL, na concentração de 0,2 μM inibiu COX-1 (79,5% ± 0,6) e COX-2 (56,0% ± 3,8), com um perfil de inibição similar ao observado para indometacina na mesma concentração (93,0 ± 2,6 e 79,0% ± 1,5, respectivamente), apresentando inibição de COX-1 em maior proporção do que COX-2. Além disso, indometacina inibiu de forma mais eficaz, tanto COX-1 como COX-2 quando comparado a FGAL. No teste de2,2-difenil-1-picriidrazila(DPPH), FGAL, na concentração de 0,3 mM, mostrou alta atividade sequestrante radicalar. Estes resultados inferem que a fase aquosa, a fase acetato e FGAL obtidos das partes aéreas de Piptadenia stipulacea são capazes de modular a antinocicepção e a resposta inflamatória aguda.O flavonoide FGAL inibe COX-1 e COX-2, provavelmente por sua capacidade de sequestrar radicais livres, sendo este um dos seus mecanismos de ação na nocicepção e inflamação. Além disso, os resultados encontrados corroboram com o uso popular de Piptadenia stipulacea por suas propriedade anti-inflamatória.

Les FGFs (fibroblast growth factor) sont de petits peptides de faible poids moléculaire généralement secrétés et présents chez tous les métazoaires. Les FGFs réalisent leur fonction en se liant à leurs récepteurs FGFRs. La liaison au récepteur peut activer trois voies de signalisation intracellulaires majeures : PLCgamma/PKC, PI3K/Akt et Ras/MAPK. Les travaux de ma thèse ont consisté en une étude comparative à la fois évolutive et fonctionnelle de la spécificité/affinité des couples FGFs/FGFRs chez les chordés. En utilisant différentes approches bioinformatiques nous avons pu éclaircir plusieurs points, notamment sur l’évolution de la famille des FGFs chez les chordés. Ainsi, nous avons pu mettre en évidence la présence de huit FGFs chez l’amphioxus, dont un orthologue d’amphioxus pour chaque groupe de paralogie de vertébrés, plus un FGF sans orthologue apparent chez les vertébrés. Nous avons aussi mis en évidence la très bonne conservation des différentes structures et positions impliquées dans l’interaction des complexes FGF/FGFR/HS (HS pour Heparan Sulfate) entre l’amphioxus et les différents vertébrés, ainsi que quelques particularités structurales spécifiques des céphalochordés. L’étude du profile d’expression par hybridation in situ des huit FGFs et des trois isoformes FGFRs que nous avons isolés nous a permis d’assigner un rôle potentiel pour chaque partenaire et de mettre en évidence les similitudes et différences d’expression avec les autres chordés. En complétant ces profiles par des profiles quantitatifs d’expression nous avons pu mettre en évidence des couples d’interaction FGF/FGFR potentiels durant les différentes étapes du développement embryonnaire.

Dissertação de Mestrado Integrado em Medicina Veterinária
Com o objectivo de conhecer alguns dos agentes infecciosos que afectam a população felina da Associação dos Amigos dos Animais Abandonados da Moita, e relacionar a sua eventual presença com as alterações clínicas apresentadas pelos animais em questão, nomeadamente a Gengivo-Estomatite Crónica Felina (GECF) e a Doença Respiratória Felina (DRF), foram avaliados neste estudo 50 felinos, incluídos aleatoriamente. A cada animal, e após exame clínico, foram colhidas as amostras de material biológico apropriado para realização de hemograma, detecção de anticorpos contra o Vírus da Imunodeficiência Felina (FIV) e de antigénio do Vírus da Leucemia Felina (FeLV), detecção de ácido nucleico de Herpesvírus Felino tipo 1 (FHV-1) e Calicivírus Felino (FCV), e pesquisa de Candida spp. O FIV e FeLV foram detectados por imunocromatografia de membrana, o FHV-1 por PCR em tempo real, o FCV por RT-PCR convencional e as leveduras isoladas em Sabouraud dextrose agar foram posteriormente identificadas quanto ao género e espécie. Constatou-se que, dos 50 animais, 22% eram positivos para FIV, 10% para FeLV, 62% para FHV-1 e 26% para FCV. Em relação às leveduras, foi detectada a presença de C. silvicola (n=3), C. valida (n=1) e C. parapsilosis (n=1). As associações estabelecidas entre a presença do vírus e determinada manifestação clínica que apresentaram significado estatístico foram: a presença de úlceras linguais em animais com FCV e co-infecção FCV / FIV; o desenvolvimento de estomatite nos animais infectados unicamente com FCV, FIV ou FeLV, e nas co-infecções FCV / FIV, FCV / FeLV, e FHV-1 / FeLV; a manifestação de gengivite de grau 2 ou 3 nos animais com FCV; e a ausência de úlceras linguais nos animais com infecção por FHV-1. O animal em que foi detectada a presença de C. parapsilosis apresentava gengivite ligeira, corrimento ocular e, a nível hematológico, leucocitose com linfocitose e monocitose. O animal infectado com C. valida exibia apenas estomatite ligeira e corrimento nasal, e os animais com C. silvicola revelaram gengivite ligeira, estomatite, úlceras linguais, corrimento ocular e nasal, e leucocitose com neutrofilia, linfocitose e monocitose. Nenhuma destas alterações revelou associação estatisticamente significativa com a presença da levedura. Para uma correcta avaliação da prevalência destes agentes infecciosos em populações errantes felinas e sua associação a GECF e DRF, deverão ser realizados estudos mais extensos quanto ao número de animais envolvidos. Por outro lado, considerando a escassa informação sobre a microbiota micológica da cavidade oral dos felinos, a detecção de Candida spp. contribuiu para um melhor conhecimento nesta área, sendo que a sua influência na etiologia da GECF e da DRF, deverá também ser estudada com maior profundidade.
ABSTRACT - Detection of Feline Immunodeficiency Virus, Feline Leukemia Virus, Feline Calicivirus, Feline Herpesvirus-1 and Candida spp. in stray cats and possible association with Feline Gingivostomatitis and Feline Respiratory Disease - The aim of this study was to analyze the viral and mycological microbiota of cats’ mouth and its relationship with the clinical symptoms, especially with Feline Gingivo-Stomatitis (FGS) and Feline Respiratory Disease (FRD), and infection with Feline Immunodeficiency Virus (FIV) and Feline Leukaemia Virus (FeLV), both able to induce immunodeficiency. The test group included 50 cats from the Associação dos Amigos dos Animais Abandonados da Moita, that were subjected to clinical examination with collection of biological samples for serological detection of Feline Leukemia Virus (FeLV) antigen and Feline Immunodeficiency Virus (FIV) antibodies, detection of Candida spp. and viral nucleic acid of Feline Herpesvirus (FHV-1) and Feline Calicivirus (FCV). FIV and FeLV were detected by immunochromatography membrane, FHV-1 by real time PCR, FCV by RT-PCR, and the yeasts by mycological culture and then identified to genus and species. Within the 50 cats sampled, 22% (11/50) were FIV seropositive, 10% (5/50) FeLV, 62% (31/50) FHV-1 and 26% (13/50) FCV. Regarding the yeasts, C. silvicola (n=3), C. valida (n=1) and C. parapsilosis (n=1), were detected. The associations between the agent detected and the clinical sign shown, that were statistically relevant were: the presence of tongue ulceration within FCV and FCV / FIV infected animals; the development of stomatitis in cats with FCV, FIV, FeLV, and FCV / FIV, FCV / FeLV, and FHV-1 / FeLV; moderate to severe gingivitis in FCV infected cats; and the absence of tongue ulceration in FHV-1 infected cats. The cat with C. parapsilosis showed mild gingivitis, ocular discharge, and hematological findings were leucocytosis with lymphocytosis and monocytosis. Mild gingivitis and nasal discharge were presented by the C. valida infected animal, while the C. silvicola infected animals showed mild gingivitis, stomatitis, tongue ulceration, ocular discharge, nasal, discharge, and leucocytosis with neutrophilia, lymphocytosis and monocytosis. Because of the small size of the sample, none of the clinical findings were statistically associated with yeasts presence. Once again, due to sampling issues, a more thorough analysis should be performed to correctly evaluate the true prevalence of these infectious agents in stray feline population. On the other hand, considering the lack of information regarding the mycological microbiota of feline oral cavity, the identification in our samples of yeasts included in the Candida genus, will certainly prove helpful. Furthermore, the role of C. valida, C. parapsilosis and C. silvicola in FGS and FRD should be deeply evaluated.

Comme en météorologie et en océanographie, l'assimilation de données permet de combiner de façon optimale les modèles décrivant l'évolution de la composition chimique et la variété des observations disponibles. Elle est utilisée dans ce travail pour caractériser les distributions de l'ozone (O3) et du protoxyde d'azote (N2O) dans le but d'en tirer une information sur les phénomènes couplés de chimie et de dynamique dans la région de la haute troposphère et basse stratosphère (UTLS). Ce travail s'appuie sur deux outils complémentaires à Météo-France : l'un est basé sur le modèle global de chimie-transport MOCAGE et le logiciel d'assimilation multi-méthodes PALM du CERFACS exploité pour mettre en oeuvre une méthode d'assimilation variationnelle 3D-FGAT; l'autre est une extension du système opérationnel d'assimilation météorologique ARPEGE utilisant la méthode variationnelle incrémentale 4D-Var. D'une part, les champs assimilés (analyses de MOCAGE-PALM) sont utilisés pour l'étude de la chimie et la dynamique stratosphérique polaire ainsi que pour le suivi du transport méridien et des échanges entre la troposphère et la stratosphère. D'autre part, l'assimilation couplée chimie-dynamique dans ARPEGE est utilisée pour évaluer l'impact dynamique des observations d'ozone dans la région de l'UTLS
As in meteorology and oceanography, data assimilation combines in an optimal way chemistry-transport models and observations. In this work, the assimilation of remote-sensing chemical measurements of ozone (O3) and nitrous oxide (N2O) aims at better characterizing their three-dimensional distributions. The objective is to get insight into the coupled chemical and dynamical phenomena in the upper troposphere - lower stratosphere (UTLS). This work uses two complementary tools in Météo-France: one is based on the three dimensional chemistry and transport model MOCAGE and the PALM software of CERFACS using the 3D-FGAT variational technique; the other is an extension of the operational suite of the numerical weather prediction ARPEGE using the 4D-Var variational technique. On one hand, the assimilated fields (MOCAGE-PALM analyses) are used for the study of the polar stratospheric chemistry and dynamics and also for the meridional transport and stratosphere-troposphere exchanges. On the other hand, the chemistry-dynamics coupled assimilation in ARPEGE is used to assess the dynamical impact of ozone observation in the UTLS region

Alzheimer's disease (AD) is an incurable neurodegenerative disorder, and the most common form of dementia, characterised neuropathologically by Aβ plaques and tau tangles. Although the late-onset form of AD (LOAD) is highly heritable (-80%), genetic studies to date have only accounted for approximately half of this. Identification of the remaining risk may require new approaches. In this thesis three candidate genes/loci (CNTN2, FGA and SPARCL 1), encoding putative LOAD cerebro-spinal fluid biomarkers (Contactin-2, Fibrinogen alpha-chain and Sparc-like-1), have been subjected to complementary genetic approaches to unearth novel LOAD risk alleles. An 'LD-aware' meta-analysis of three LOAD genome-wide datasets was conducted to investigate disease association with common (MAF>5%) variation in each candidate gene. Secondly, SOliD next-generation resequencing of 150 samples (75 LOAD, 75 controls), PCR enriched for candidate loci, was conducted to identify novel rare variation. Selected variants were subsequently validated and replicated in larger series (n=1453) using TaqMan genotyping. Meta-analysis revealed linked SNPs (rs7523477, rs4951168) downstream of CNTN2 associated with LOAD (p=3x10-5, OR=1.23(1.01-1.49) n=4898). However, this has not been replicated by subsequent GWAS. Resequencing identified 28 novel rare variations over all candidate loci. A SPARCL 1 variant (located at 88451921 (hg19)) showed association with LOAD in a UK population (p=0.023, OR=1.95(1.1 0-3.46)). Replication of this association will be required in independent series. In the post-GWAS era, new approaches to identify the remaining heritability of LOAD must be embraced. Not only will the identification of new mutations conferring risk for Alzheimer's disease benefit diagnosis, it will also foster a greater understanding of disease pathways - to which treatments can be targeted.

Les "heparin-binding growth factors" (HBGFs) encore appelés "fibroblast growth factors" (FGFs) constituent une famille de facteurs de croissance (FC) qui, chez les vertébrés, peuvent induire in vitro la prolifération mais aussi la différenciation de nombreux types cellulaires. Leur rôle in vivo est encore peu connu. D'autre part, la présence d'HBGFs chez les invertébrés n'a jamais été rapportée. Les néreidiens ont été choisis pour leur capacité de croître continuellement, de régénérer intégralement des parties amputées et certaines espèces présentent une néoangiogenèse importante à l'approche de la reproduction. Cependant, la nature des molécules intervenant dans les zones de prolifération cellulaire intense est encore ignorée. Nous avons pu montrer chez n. Diversicolor l'existence de FC apparentés aux FGFs de vertébrés. Les HBGFS de néreidiens (nHBGFs) sont affines pour l'héparine et capables de stimuler la prolifération de fibroblastes en culture. Ces FC possèdent des poids moléculaires (PM) proches de 20 kDa et un point isoélectrique de 6,4. Une classe de sites de fixation à haute affinite au FGF basique (Kd=40 pM ; capacité=140 fmoles/mg de protéines) correspondant à des formes récepteurs de pm apparent de 165, 105 et 55 kDa et une classe de sites de fixation à basse affinité (Kd=4 nM ; capacité=25 pmoles/mg de protéines) ont été mises en évidence sur des préparations membranaires de N. Diversicolor. Nous avons montré, par ailleurs, que les nHBGFs entrent en compétition avec le FGF basique au niveau de ses sites de fixation spécifiques. Le dosage des nHBGFs et de leurs sites de fixation dans différentes conditions biologiques semble indiquer que l'activité des nHBGFs pourrait être régulée au cours des processus de croissance par l'expression des sites de fixation.

I detta projekt analyseras utmattningsbrott orsakade av ytdefekter i höghållfast stål som utsätts för fler än tio miljoner cykliska belastningar. Vanligen orsakas utmattningsbrott i denna region av interna materialdefekter där brottytan ofta innehåller ett område med grövre morfologi - fine granular area (FGA). FGA är en ackumulerad skada som bildas under sprickinitieringsstadiet och utgör cirka 99 % av den totala utmattningslivslängden. Resterande 1 % utgörs av spricktillväxt. På grund av detta är mekanismen som initierar sprickor i detta skede essentiell. Om FGA kan observeras vid ytinitierade utmattningsbrott för material som utsätts för fler än tio miljoner cykliska belastningar, är ännu inte fastställt. . Det här projektet syftar till att undersöka om FGA kan observeras i ytinitierat utmattningsbrott gällande material med väldigt långa livslängder, samt till att utreda hur ytinitieringar påverkar utmattningslivslängden. För att söka svar på dessa frågor utförs utmattningsprovning med ultraljudsutrustning, följt av karaktärisering av brottytorna i svepelektronmikroskop för att studera de morfologiska förändringarna. Vidare utförs finita element analyser med mjukvaran ABAQUS för att jämföra den maximala huvudspänningen mellan prov med, respektive utan ytdefekter. Resultatet från ABAQUS visar att proven med hårdhetsintryck utsätts för en större maximal huvudspänning än proven utan hårdhetsintryck, därigenom kan skillnaden i livslängder förklaras. . Testresultaten från utmattningsprovningen presenteras i ett S-N diagram som visar spänningsamplituden i förhållande till materialets livslängd. De analyserade bilderna från svepelektronmikroskopet av ytinitierat utmattningsbrott visar en antydan till FGA i två av 20 prov. Däremot tycks sprickorna, i samtliga fall, initiera på grund av ackumulering av plastisk deformation i ytan. Interna materialdefekter orsakade inte utmattningsbrott i något av de 20 testade proverna med ytdefekter. Två prover utan ytdefekter genomgick samma process och för båda dessa introducerades en spricka på grund av interna materialdefekter, båda innehöll ett tydligt FGA. Sammanfattningsvis indikerar resultaten från denna studie att FGA inte är lika uppenbara och eventuellt lika vanligt förekommande vid ytinitierat utmattningsbrott av höghållfasta stål med mycket långa livslängder. Även att ytdefekter introducerar en högre maximal huvudspänning i provets centrum, vilket resulterar i en kortare utmattningslivslängd.