962 resultados para Self-Formation
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Dissertação apresentada como requisito parcial para a obtenção do grau de mestre em Estatística e Gestão de Informação.
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The S100 proteins are 10-12 kDa EF-hand proteins that act as central regulators in a multitude of cellular processes including cell survival, proliferation, differentiation and motility. Consequently, many S100 proteins are implicated and display marked changes in their expression levels in many types of cancer, neurodegenerative disorders, inflammatory and autoimmune diseases. The structure and function of S100 proteins are modulated by metal ions via Ca2+ binding through EF-hand motifs and binding of Zn2+ and Cu2+ at additional sites, usually at the homodimer interfaces. Ca2+ binding modulates S100 conformational opening and thus promotes and affects the interaction with p53, the receptor for advanced glycation endproducts and Toll-like receptor 4, among many others. Structural plasticity also occurs at the quaternary level, where several S100 proteins self-assemble into multiple oligomeric states, many being functionally relevant. Recently, we have found that the S100A8/A9 proteins are involved in amyloidogenic processes in corpora amylacea of prostate cancer patients, and undergo metal-mediated amyloid oligomerization and fibrillation in vitro. Here we review the unique chemical and structural properties of S100 proteins that underlie the conformational changes resulting in their oligomerization upon metal ion binding and ultimately in functional control. The possibility that S100 proteins have intrinsic amyloid-forming capacity is also addressed, as well as the hypothesis that amyloid self-assemblies may, under particular physiological conditions, affect the S100 functions within the cellular milieu.
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Dissertação apresentada como requisito parcial para obtenção do grau de Mestre em Estatística e Gestão de Informação.
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A thesis submitted in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Information Systems.
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S100A6 is a small EF-hand calcium- and zinc-binding protein involved in the regulation of cell proliferation and cytoskeletal dynamics. It is overexpressed in neurodegenerative disorders and a proposed marker for Amyotrophic Lateral Sclerosis (ALS). Following recent reports of amyloid formation by S100 proteins, we investigated the aggregation properties of S100A6. Computational analysis using aggregation predictors Waltz and Zyggregator revealed increased propensity within S100A6 helices HI and HIV. Subsequent analysis of Thioflavin-T binding kinetics under acidic conditions elicited a very fast process with no lag phase and extensive formation of aggregates and stacked fibrils as observed by electron microscopy. Ca2+ exerted an inhibitory effect on the aggregation kinetics, which could be reverted upon chelation. An FT-IR investigation of the early conformational changes occurring under these conditions showed that Ca2+ promotes anti-parallel β-sheet conformations that repress fibrillation. At pH 7, Ca2+ rendered the fibril formation kinetics slower: time-resolved imaging showed that fibril formation is highly suppressed, with aggregates forming instead. In the absence of metals an extensive network of fibrils is formed. S100A6 oligomers, but not fibrils, were found to be cytotoxic, decreasing cell viability by up to 40%. This effect was not observed when the aggregates were formed in the presence of Ca2+. Interestingly, native S1006 seeds SOD1 aggregation, shortening its nucleation process. This suggests a cross-talk between these two proteins involved in ALS. Overall, these results put forward novel roles for S100 proteins, whose metal-modulated aggregation propensity may be a key aspect in their physiology and function.
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Dissertação apresentada na Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa para a obtenção do grau de Mestre em Engenharia Química e Bioquímica
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Infection of Swiss/NIH mice with Leishmania major was compared with infection in isogenic resistant C57BL/6 and susceptible BALB/c mice. Swiss/NIH mice showed self-controlled lesions in the injected foot pad. The production of high levels of interferon-g (IFN-g) and low levels of interleukin-4 (IL-4) by cells from these animals suggests that they mount a Th1-type immune response. The importance of the indigenous microbiota on the development of murine leishmaniasis was investigated by infecting germfree Swiss/NIH in the hind footpad with L. major and conventionalizing after 3 weeks of infection. Lesions from conventionalized Swiss/NIH mice were significantly larger than conventional mice. Histopathological analysis of lesions from conventionalized animals showed abscesses of variable shapes and sizes and high numbers of parasitized macrophages. In the lesions from conventional mice, besides the absence of abscess formation, parasites were rarely observed. On the other hand, cells from conventional and conventionalized mice produced similar Th1-type response characterized by high levels of IFN-g and low levels of IL-4. In this study, we demonstrated that Swiss/NIH mice are resistant to L. major infection and that the absence of the normal microbiota at the beginning of infection significantly influenced the lesion size and the inflammatory response at the site of infection.
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É de extrema importância implementar nos edifícios uma cultura de segurança. Nesse sentido, no presente trabalho intitulado “Organização e Gestão da Segurança Contra Incêndios”, realizado na forma de dissertação, são abordados os diversos aspetos que permitem aos edifícios estar devidamente organizados e geridos para fazer face a situações de emergência. Neste trabalho, inicialmente é formado um enquadramento ao tema da Segurança Contra Incêndios em Edifícios, com uma abordagem ao estado da arte e às medidas de autoproteção exigidas na legislação vigente. Devido à importância e ao dever legal imputado aos edifícios, de possuir uma estrutura interna, capaz de atenuar os prejuízos humanos e materiais decorrentes de uma situação de emergência, esta dissertação detalha as diversas exigências de estruturação e formação dos elementos que detêm responsabilidades na segurança contra incêndios. Para testar as medidas implementadas, criar rotinas de comportamento, assim como para aperfeiçoar os procedimentos de atuação, é essencial a realização periódica de simulacros. Esta temática é abordada neste trabalho de forma consistente, salientando a sua aplicação prática, que deve ser cuidadosamente planeada, executada e avaliada. Para complementar esta dissertação, é apresentado um caso prático, sendo dispostas medidas para a organização e gestão da segurança contra incêndios no Hotel Dom Henrique.
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Advanced glycation end-products are Maillard reaction products that are found in thermal processed food. This compounds are often referred as unhealthy for human diet, namely because of their capacity to form amino-acid dimers. There is a broad range of answers to get about how these products are formed, how they interact with the organism and how these reactions can be inhibited to prevent the referred effects. Some compounds from garlic are thought to be able to inhibit these reactions. This study using spectrophotometric, High Performance Liquid Chromatography-Tandem Mass Spectrometry (HPLC-MS/MS) and Fourier transformed infrared spectroscopy (FTIR) analysis, helps to understand better not only not only the effect of some compounds obtained from garlic, diallyl sulfide (DAS), diallyl disulfide (DADS) and diallyl trisulfide (DATS), on these AGEs production reaction, but also helped to understand better the reaction itself.
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Myoglobin (Mb) is among the cardiac biomarkers playing a major role in urgent diagnosis of cardiovascular diseases. Its monitoring in point-of-care is therefore fundamental. Pursuing this goal, a novel biomimetic ionophore for the potentiometric transduction of Mb is presented. It was synthesized by surface molecular imprinting (SMI) with the purpose of developing highly efficient sensor layers for near-stereochemical recognition of Mb. The template (Mb) was imprinted on a silane surface that was covalently attached to silica beads by means of self-assembled monolayers. First the silica was modified with an external layer of aldehyde groups. Then, Mb was attached by reaction with its amine groups (on the external surface) and subsequent formation of imine bonds. The vacant places surrounding Mb were filled by polymerization of the silane monomers 3-aminopropyltrimethoxysilane (APTMS) and propyltrimethoxysilane (PTMS). Finally, the template was removed by imine cleavage after treatment with oxalic acid. The results materials were finely dispersed in plasticized PVC selective membranes and used as ionophores in potentiometric transduction. The best analytical features were found in HEPES buffer of pH 4. Under this condition, the limits of detection were of 1.3 × 10−6 mol/L for a linear response after 8.0 × 10−7 mol/L with an anionic slope of −65.9 mV/decade. The imprinting effect was tested by preparing non-imprinted (NI) particles and employing these materials as ionophores. The resulting membranes showed no ability to detect Mb. Good selectivity was observed towards creatinine, sacarose, fructose, galactose, sodium glutamate, and alanine. The analytical application was conducted successfully and showed accurate and precise results.
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6th Real-Time Scheduling Open Problems Seminar (RTSOPS 2015), Lund, Sweden.
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Power law (PL) distributions have been largely reported in the modeling of distinct real phenomena and have been associated with fractal structures and self-similar systems. In this paper, we analyze real data that follows a PL and a double PL behavior and verify the relation between the PL coefficient and the capacity dimension of known fractals. It is to be proved a method that translates PLs coefficients into capacity dimension of fractals of any real data.
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Advances in technology have produced more and more intricate industrial systems, such as nuclear power plants, chemical centers and petroleum platforms. Such complex plants exhibit multiple interactions among smaller units and human operators, rising potentially disastrous failure, which can propagate across subsystem boundaries. This paper analyzes industrial accident data-series in the perspective of statistical physics and dynamical systems. Global data is collected from the Emergency Events Database (EM-DAT) during the time period from year 1903 up to 2012. The statistical distributions of the number of fatalities caused by industrial accidents reveal Power Law (PL) behavior. We analyze the evolution of the PL parameters over time and observe a remarkable increment in the PL exponent during the last years. PL behavior allows prediction by extrapolation over a wide range of scales. In a complementary line of thought, we compare the data using appropriate indices and use different visualization techniques to correlate and to extract relationships among industrial accident events. This study contributes to better understand the complexity of modern industrial accidents and their ruling principles.
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Self-inflicted burns (SIB) are responsible for 2-6% of admissions to Burn Units in Europe and North America, and for as many as 25% of admissions in developing nations. Recently, a promising new tool was proposed to stratify SIB patients in the following subgroups: "typical", "delirious", and "reactive". However, as far as the authors know, the clinical usefulness of this instrument has not yet been validated by others. We retrospectively reviewed the clinical records of 56 patients admitted to our Burn Unit with the diagnosis of SIB injury in the past 14 years. The following parameters were evaluated: demographic features; psychiatric illness; substance abuse; mechanism of injury; burn depth, total body surface area (TBSA) involved, Abbreviated Burn Severity Index (ABSI); length of hospital stay, and mortality. All patients were followed up by a psychologist and a psychiatrist, and were classified according to the SIB-Typology Tool, into three classes: "typical", "delirious" and "reactive". There was a slight predominance of the "typical" type (44.6%), followed by the "delirious" type (30.4%), and, finally the "reactive" type (25.0%). Mortality was significantly higher in the "typical" subgroup. In conclusion, the SIB-Typology Tool appears to be a valuable instrument in the clinical management of SIB patients.