A melatonina produzida pela glândula pineal apresenta diversas ações reguladoras da homeostase dinâmica interna de mamíferos. Suas ações abrangem tanto a regulação de funções endógenas circadianas e sazonais em situações de higidez quanto durante processos fisiopatológicos. O presente trabalho avalia o efeito dos moduladores de processos inflamatórios corticosterona, TNF e IFNy; sobre o metabolismo da glândula pineal. Os resultados aqui apresentados mostram que: 1- Corticosterona potencia a síntese de noradrenalina in vivo e in vitro na vigência de estimulação β-adrenérgica, mas inibe a produção induzida por estimulação concomitante α e β-adrenérgica. 2- Este efeito é dependente de ativação de GR e não altera a captação extraneuronal de catecolaminas. 3- Corticosterona aumenta a expressão do transcrito aa-nat e a atividade das enzimas AA-NAT e HIOMT. 4 Corticosterona inibe o acúmulo nuclear de NF-κB. 5- A inibição farmacológica da via NF-κB mimetiza o efeito potenciador da corticosterona sobre a produção hormonal da pineal. 6 IFN-y inibe a via NF-κB. 7 - IFN-y potencia a produção de melatonina pela glândula pineal. 8- TNF ativa a via NF-κB. 9 TNF inibe a produção de melatonina pela pineal. 10- TNF inibe transitoriamente a expressão do transcrito aa-nat e NAS. 11 A transitoriedade deste efeito é dependente de neosíntese protéica. O presente trabalho mostra que a glândula pineal está aparelhada para responder a diferentes agentes moduladores de processos inflamatórios além de fortalecer e darem base para a hipótese da existência de um eixo imune-pineal central no controle de processos patológicos em mamíferos. / The melatonin, synthetized by the pineal gland, exihibits a number of regulatory activities on the internal dynamic homeostasis of mammals. These functions are related to the regulation of endogenous circadian and seasonal rhythms during healthy and physiopathological processes. This study evaluates the effects of the inflammatory modulators, corticosterone, TNF and IFN- y, over the pineal gland metabolism. The results presented here show that: 1 - Corticosterone enhances the synthesis of norepinephrine in vivo and in vitro in the presence of β-adrenergic stimulation, but inhibits the hormonal production when both, αand βadrenoceptors, are activated. 2 - This effect depends on the GR activation and does not interfere in the extraneuronal uptake of catecholamines. 3 - Corticosterone increases the expression of the aanat transcript and also the enzymatic activity of AA-NAT and HIOMT. 4 - Corticosterone inhibits the nuclear accumulation of NF-κB. 5 - The pharmacological inhibition of NF-κB pathway mimics the effect of corticosterone on the hormonal production in pineal. 6 - IFN-y inhibits the NF- κB pathway. 7 - IFN-y enhances the synthesis of melatonin in the pineal gland. 8- TNF activates the NF-κB pathway. 9 - TNF inhibits the production of melatonin in the pineal gland. 10 - TNF transiently inhibits the production of the aa-nat transcript and also of NAS. 11 - This transient effect depends on the synthesis of proteins. This study shows that the pineal gland can respond to different inflammatory modulators, supporting the hypothesis of a central immune-pineal axis controlling pathological processes in mammals. .

A partir do entendimento de que as transformações do espaço compõem um movimento único e totalizante, buscamos problematizar a questão na composição das transformações que se sucedem em Sorocaba. O recorte do Eixo Sudeste nos serve como base empírica da sustentação de nossa problemática. As transformações do espaço urbano deste Município estão diretamente ligadas aos interesses de diversas escalas e níveis da realidade. Para isto, a compreensão histórica da materialização deste setor do espaço urbano, assim como sua identidade no território sorocabano nos aproxima do movimento social em suas diversas instâncias, desta forma, exploramos a possibilidade da realização de um exercício teórico de aproximar as transformações no espaço urbano de Sorocaba à reprodução da sociedade como todo. / From the understanding that the transformations of space make up a unique and totalizing movement, we try to problematize this question in the composition of the transformations that succeed in Sorocaba. The cutting of the Southeast Hub serves as an empirical basis for sustaining our problematic. The transformations of the urban space of this Municipality are directly linked to interests of different scales and levels of reality. For this, the historical understanding of the materialization of this urban space industry, as well as its identity in Sorocaba territory approaches in the social movement in its various instances, therefore we explored the possibility of carrying out a theoretical exercise to bring the changes in the urban space Sorocaba to the reproduction of society as a whole.

Around 3-8% of all women in reproductive age suffer from premenstrual dysphoric disorder (PMDD) which disenables them to live an ordinary life during the luteal phase (premenstrual phase) of the menstrual cycle. Throughout the premenstrual phase these women experience emotional, cognitive and physiological changes. Hitherto, the etiology of this disorder is unknown. Some consider the source of this state as non-biological, claiming that PMDD is a social construction imbedded in gender roles, that suggests that women should not show aggressive behavior or depressive mood unless it is during the premenstrual stage. Contradictory, research made in cognitive neuroscience claim that the origin is biological. It is assumed that the increased symptoms in women with PMDD is a result from dysfunctional sensitivity for the progesterone metabolite allopregnanolone that has a receptor in the GABAA system, hence, producing an anxious effect from high levels of allopregnanolone instead of the expected sedative, soothing effects. Research suggest that structural and functional changes occur in brain areas such as the hippocampus, parahippocampus, amygdala, cerebellum as well as in brainderived neurotrophic factor which is important for brain plasticity, growth and survival of neurons. Cognitive behaviors such as anticipation for negative stimuli, working memory and lack of cognitive control also seem to be affected by PMDD. Nonetheless, the evidence is inconsistent, the area of research face multiple issues in regards to study designs, hence making generalization at this point difficult. In sum, this essay reviews recent studies conducted in neuroscience of cognitive changes in women with PMDD, with focus on functional, structural and behavioral changes between the phases of the cycle.

Our gut microbiota is involved in human development, nutrition, and the pathogenesis of gut disorders, but has more recently been implicated as a possible mechanism in the pathophysiology of several brain disorders, including disorders of mood and affect, such as depression. Researchers have referred to this dynamic, bidirectional signaling pathway between the gut and the brain as the “gut-brain axis.” However, most research on this axis has been limited to rodent studies, and there has been little insight into the mechanism behind it. I propose that the kynurenine pathway, where tryptophan is converted to kynurenine, is a compelling mechanism mediating the gut microbiota’s influence on depression. Kynurenine is a metabolite associated with depression, and this pathway has been shown to be manipulated through probiotic (Lactobacillus reuteri) consumption. I propose to study a probiotic intervention in humans, which would assess tryptophan metabolism along the kynurenine pathway by measuring metabolites downstream of this pathway. Urine, feces and blood samples would be collected from two groups, control and probiotic treatment, on day zero and day thirty. Colonic biopsies would be obtained on day thirty, and various analyses would be run to measure metabolite concentrations from the collected samples. The results from this study will help clarify a mechanistic connection between gut microbes and depression via the kynurenine pathway. Additionally, findings could indicate that a probiotic intervention has the ability to influence depressive behavior via a two-pronged approach originating from the kynurenine pathway.

The purpose of this study is to investigate to what extent skeptical attitudes towards the European Union is driven by materialistic-, postmaterialist values and populism in different parts of Europe. To achieve this aim, the study is based on multivariate regression analysis with data utilized from the European Social survey 2014. The findings show that cultural questions associated with TAN values, such as a nationalistic resistance towards immigration, have the best ability to predict EU-skepticism over economic questions related with a subjective placement on the political left-right scale, or populism associated with a lack of trust in the state of political governance. These findings suggest that the subjective left-right scale do not structure attitudes toward the European Union to a great extent. Instead, the results of this study are in line with scholars that argue that the TAN-GAL scale as well as populism have grown in importance, as these axes of competition are both more linked with opinions on EU. These results hold for all regions in Europe that are examined in this study, although particular strong effects are found in Germany, where populism and TAN values shape attitudes towards EU to the greatest extent.

Laser beam welding applications are widely used in the industry. However, laser beam welding applications have a very small position tolerance to an offset. In this project, the offset is defined as the distance between the point, which the laser tool welds, and the point which laser tool should weld the weld joint. In other words, the offset is the position error in a welding application. To perform successful welding, the laser beam must hit the exact coordinate of the weld joints to weld the parts together. For dealing with these inaccuracy issues, tool manipulation systems can be used. In this project, an external axis is used for the precise manipulation of the laser beam welding tool as a complement to robotic nominal movement. Input data to the external axis system is obtained from an image from a vision system of the work pieces which need to be welded. Tool manipulation systems are used to manipulate tools to ensure certain position accuracy during any application. The tool manipulation system in this project has two main parts; a seam tracking system (outside this project) and an external axis system. The seam tracking system gives an on-line measurement of the offset, and that there is a feedback loop with a controller, which gives the system information about how much to manipulate the external axis module to the external axis system. The seam tracking system consists of two main parts; a camera and the seam tracking image processing program. In the seam tracking system, a camera takes images of the work pieces which shall be welded. Then the seam tracking program calculates the offset by image processing. This estimated offset is the input for the external axis system. The external axis system has three main parts; the external axis program, input-output module and the external axis module. The external axis program is the system which controls the input-output module for manipulating the external axis module in this project. The external axis module manipulates the laser beam welding tool by changing the orientation of the tool in order to reduce the offset. This project is about the external axis system. There is a relationship between the offset input and the required manipulation angle of the external axis. In this project, the required manipulation angle is the external axis angle. By using this relationship, the laser beam welding tool can be manipulated to weld in the desired position. The same system can be used in applications which require high position accuracy. The evaluation of the external axis system emphasizes that the accuracy demand of the laser beam welding applications can be satisfied by an external axis system. However, the investigated external axis system behaves in a way that when the offset is larger than it supposed to be, the speed of the TCP movement slows down.

Master of Science / Department of Chemical Engineering / James H. Edgar / 4H-silicon carbide (4H-SiC) is a wide band gap semiconductor with outstanding capabilities for high temperature, high power, and high frequency electronic device applications. Advances in its processing technology have resulted in large micropipe-free single crystals and high speed epitaxial growth on off-axis silicon face substrates. Extraordinarily high growth rates of high quality epitaxial films (>100 [Mu]m per hour) have been achieved, but only on off-axis substrates (misoriented 4° to 8° from the (0001) crystallographic plane). There is a strong incentive to procure an on-axis growth procedure, due to the excessive waste of high quality single crystal associated with wafering off-axis substrates. The purpose of this research was to develop a reliable process for homoepitaxial growth of 4H-SiC on on-axis 4H-SiC. Typically the use of on-axis SiC for epitaxial growth is undesired due to the increased probability of 3C-SiC inclusions and polycrystalline growth. However, it is believed that the presence of chlorine during reaction may reduce the presence of 3C-SiC and improve the quality of the epitaxial film. Therefore homoepitaxial SiC was deposited using methyltrichlorosilane (MTS) and ethane sources with carrier gases consisting of argon-hydrogen mixtures. Ethane was used to increase the C/Si ratio, to aid in the prevention of 3C-SiC, and to help eliminate silicon droplets deposited during epitaxial growth. Deposition occurred in a homemade, quartz, cold wall chemical vapor deposition reactor. Epitaxial films on on-axis 4H-SiC were deposited without the presence of 3C-SiC inclusions or polycrystalline SiC, as observed by defect selective etching, scanning electron microscopy and optical microscopy. Large defect free areas, [similar to]5 mm[superscript]2, with epitaxial film thicknesses of [similar to]6 [Mu]m were grown on on-axis 4H-SiC. Epitaxial films had approximately an 80%, [similar to]20 cm[superscript]-2, decrease in defect density as compared to the substrates. The growth rate was independent of face polarity and orientation of the substrate. The optimal temperature for hydrogen etching, to promote the smoothest epitaxial films for on-axis substrates (both C- and Si-polarities), is [similar to]1550 °C for 10 minutes in the presence of 2 slm hydrogen. The optimum C/Si ratio for epitaxial growth on on-axis 4H-SiC is 1; excess carbon resulted in the codeposition of graphite and cone-shaped silicon carbide defects.

Die Skelettextraktion ist besonders in der Formanalyse ein wichtiges Werkzeug. Im Rahmen des Forschungsprojektes ’Extraktion fertigungsrelevanter Merkmale aus 3D-Daten umformtechnischer Bauteile zur featurebasierten Fertigungsprozessgestaltung’ als Kooperationsprojekt zwischen der Professur Graphische Datenverarbeitung und Visualisierung an der Technischen Universität Chemnitz und des Fraunhofer-Institut für Werkzeugmaschinen und Umformtechnik Chemnitz wurde diese zur Featureerkennung umgesetzt. Dieses Dokument gibt zunächst Einblick in grundlegende Verfahren und Problemstellungen einer solchen Extraktion. Die Ergebnisse mehrerer Forschungsschwerpunkte, die sich aus den zu untersuchenden Massivumformteilen ergaben, werden vorgestellt. Hierbei besonders interessant ist die robuste Extraktion von Kurvenskeletten bei Bauteilen mit nicht-zylindrischer Hauptform, sowie bei Bauteilen mit Nebenformelementen. Desweiteren werden Nachverarbeitung und Auswertung des Kurvenskeletts, sowie verwandte Forschungsarbeiten und -ergebnisse diskutiert.

La nutrition au cours de la période postnatale précoce programme l’activité de l’axe somatotrope à l’âge adulte (GH/IGF-1). Une altération de la nutrition chez les souriceaux au cours de la lactation altère la croissance staturo-pondérale de façon permanente et augmente leurs susceptibilités à développer des pathologies cardio-métaboliques à l’âge adulte. La restriction au cours de la lactation induit une diminution des taux plasmatiques en IGF-1 et en leptine. Ceci est associé à une diminution transitoire de l’innervation de l’éminence médiane par les neurones GHRH, ce qui induit une hypoplasie hypophysaire permanente en cellules somatotropes. Durant ma thèse, j’ai étudié l’impact de la nutrition périnatale sur la mise en place de l’axe somatotrope, notamment les mécanismes impliqués dans la régulation du développement des neurones GHRH. Les cultures d’explants de noyaux arqués issus de souriceaux normalement nourris indiquent que l’IGF-1 stimule de façon préférentielle la croissance axonale des neurones GHRH par l'intermédiaire des voies PI3K/AKT et MAPK. La leptine présenterait quant à elle un effet plus global sur les neurones du noyau arqué, stimulant la croissance axonale des neurones GHRH et des neurones orexigène à NPY/AgRP. Les neurones GHRH issus de souris restreintes sont quant à eux résistants à la stimulation de la croissance axonale par l’IGF-1 ou la leptine. Concernant l’IGF-I, cette résistance est associée à une altération des capacités de phosphorylation de la voie PI3K/AKT, tandis que celles de l’IGF-1R et de la voie MAPK ne sont pas altérées. / Nutrition during lactation programs the activity of the somatotropic axis (GH/IGF-1). Alteration of nutrition during the early postnatal period in mice induces increased susceptibility to develop cardiovascular and metabolic pathologies later in life. Nutritional restriction during lactation permanently alters growth of mice. Ten days old restricted pups present decreased plasmatic level of IGF-1 and Leptin. They also present a transient alteration of median eminence innervation by GHRH neurons, which induce a permanent somatotroph cells (GH) hypoplasia in pituitary. The aim of my thesis was to study the impact of nutrition during the perinatal period on the programming of the somatotropic axis, notably the cellular and molecular mechanisms involved in the regulation of GHRH neuronal development. In vitro cultures of arcuate nucleus explants of hypothalamus from normally fed pups indicate that IGF-1 preferentially stimulates axonal growth of GHRH neurons by its signaling pathways PI3K/AKT and MAPK. Leptin present a more global effect and is able to stimulate axonal growth of arcuate nucleus neurons, including GHRH and AgRP neurons. GHRH neurons from restricted pups are resistant to the stimulation of axonal growth by IGF-1 or leptin. Regarding IGF-1, this resistance is associated with an alteration of phosphorylation capacities of the PI3K/AKT pathway, whereas those from IGF-1R and MAPK are not altered.

The typical methodology for analytically designing a wind turbine blade is by means of blade element momentum (BEM) theory, whereby the aerofoil angle of attack is optimized to achieve a maximum lift-to-drag ratio. This research aims to show that an alternative optimisation methodology could yield better results, especially in gusty and turbulent wind conditions. This alternative method looks at increasing the aerofoil Reynolds number by increasing the aerofoil chord length. The increased Reynolds number generally increases the e_ectiveness of the aerofoil which would result in a higher or similar lift-to-drag ratio (even at the decreased angle of attacked require to maintain the turbine thrust coe_cient). The bene_t of this design is a atter power curve which causes the turbine to be less sensitive to uctuating winds. Also, the turbine has more torque at startup, allowing for operatation in lower wind speeds. This research is assumed to only be applicable to small wind turbines which operated in a low Reynolds number regime (<500 000), where Reynolds number manipulation is most advantageous.