Objetivo: Avaliar o uso de antitrombóticos em pacientes com fibrilação atrial (FA) em hospital cardiológico no Brasil (InCor).Métodos e resultados: Um estudo observacional transversal analisou os prontuários de todos os pacientes atendidos no InCor em cada um de 5 dias separados no ano de 2002 (Fase 1), sendo prospectivamente reanalisados após 1 ano (Fase 2). A prevalência da FA nos 3764 prontuários analisados foi de 8%. Antiplaquetários foram prescritos para 21,26% e 19,93%, anticoagulantes para 46,51% e 57,81%, e 32,23% e 22,26% não usavam nenhum antitrombótico nas Fases 1 e 2, respectivamente. Somente 15,60% e 23,25% apresentavam níveis de RNI terapêuticos.Conclusão: A anticoagulação é subutilizada nos pacientes com FA apesar do fato de serem tratados por cardiologistas em um hospital universitário / Objective: To assess antithrombotic therapy among atrial fibrillation (AF) patients in a Brazilian University Heart Hospital (InCor).Methods and results: A cross sectional study analyzed the charts of all patients treated at InCor in 5 separate days of 2002 (Phase 1), and prospectively reviewed them after one year (Phase 2). The prevalence of AF in the 3,764 assessed charts was of 8.0%. Antiplatelets were prescribed to 21.26% and 19.93%, anticoagulants to 46.51% and 57.81%, and 32.23% and 22.26% were not receiving any antithrombotic in Phases 1 and 2, respectively. Only 15.60% and 23.25% were within INR therapeutic range.Conclusion: Anticoagulation is underused in AF patients besides the fact of being treated by cardiologists in a University Hospital

Medium chain fatty acids (MCFAs) are essential molecules for a wide range of pharmaceutical, biotechnological, and industrial applications. These are naturally occurring saturated or unsaturated fatty acids containing 6-12 carbons with complex and pH sensitive aggregation. Medium chain fatty acids such as capric acid (C10) or lauric acid (C12) have additionally been shown to exhibit antibacterial activity. A number of studies have observed the aggregation behavior of long chain fatty acid using the titration curves by molecular dynamic (MD) simulations.  In this study, we performed constant-pH coarse-grained MD simulations to determine pKa values and titration behavior using a two-states model for C10 and C12. In the simulations, pH was varied between 2 to 8 and pKa values were determined using the Hill equation. The pKa for C10 (capric acid) was found to be 4.8 and for C12 (lauric acid) 5.4, in good agreement with the literature values (4.9 and 5.3, respectively).

The world's energy supply today mainly consists of fossil fuels and nuclear power. Moving away from the use of these energy resources to renewable energy sources is considered a prerequisite for a sustainable future. In order to implement this change, it is necessary for renewable energy sources to be environmentally, technically and economically sustainable. A major challenge encountered in terms of technological sustainability is the intermittent nature of renewable energy sources. As the share of renewable electricity increases in the system, the electricity grid is facing new challenges such as increased instability of the frequency and capacity shortages. In order to meet these new challenges an increased flexibility from electricity users is proposed as a solution. Flexibility can be achieved either by controlling the use of electricity or utilizing energy storages. If different electric loads are to be controlled in a property, data regarding the power use of the loads must first be collected with a high time resolution in order to be able to properly analyze the data. Measures to shift or reduce the power peaks in a property can then be suggested and implemented. A battery storage can help reduce power peaks or shift loads in time and if done on a large scale that would reduce the strain on the entire Swedish grid. One of the ancillary services that the battery could offer is frequency regulation. Using energy storages for such an application could also provide a secondary revenue stream, aside from the revenue stream from peak shaving, and increase the profitability of the storage. Sweden has seen a dramatic increase in electric vehicles over the last decade and charging of the vehicles has become an issue for many property owners as it often creates power peaks. The data collection regarding power use in properties performed in during this thesis showed that valuable data can be collected with the method and material used. With a battery price of 3000 SEK/kWh the payback time for a battery system can be reduced from 17,9 to 7,8 years if it is used for frequency regulation during the night. If power-intensive loads such as electric vehicle charging are added to the model the payback period decreases to 6,1 years. With these results in mind, it can be concluded that the profitability of a battery storage can increase to the extent that the investment is of economic viability. In addition, the investment helps to improve the stability of the Swedish grid. The results are found to be relatively consistent with those of other similar studies. / <p>Digital presentation</p>

Understanding the size dependent dissolution of engineered nanoparticles is one important aspect in addressing the potential environmental and health impacts of these materials as well as their long-term stability. In this study, experimental measurements of size dependent dissolution of well-characterized zinc oxide (ZnO) nanoparticles with particle diameters in the range of 4 to 130 nm have been measured and compared at circumneutral pH (pH 7.5). Enhanced dissolution was found for the smaller particles with the largest enhancement observed in Zn2+(aq) concentrations for 4 nm diameter ZnO nanoparticles compared to larger-sized particles. Interestingly, size dependent dissolution was observed even though the nanoparticles aggregated with hydrodynamic diameters on the order of 1-3 m in diameter. Although these results are found to be in qualitative agreement with theoretical predictions used to predict the dissolution of solids, a linearized form of the Kelvin equation to calculate a bulk dissolution value for ZnO and a surface free energy yielded quantities inconsistent with known literature values. It is therefore concluded that deviations from solubility behavior from classical thermodynamics are due to a lack of the detailed knowledge of the surface free energy as well as its dependence on the details of the surface structure, surface properties, including the presence of different surface crystal facets and adsorbed ligands, as well of aggregation state. The presence of citric acid significantly enhances the extent of ZnO dissolution for all sizes such that no significant differences were observed for total Zn2+(aq) concentrations for nanoparticles between 4 to 130 nm. This can be attributed to ligand enhanced dissolution of ZnO nanoparticles where there is no dependence on size. Adsorption of citrates onto ZnO nanoparticles was observed using ATR-FTIR spectroscopy. A reversal of surface charge of ZnO nanoparticles was observed upon adsorption of citrates. Adsorption of negatively charged Cit3- onto ZnO nanoparticles make the surfaces negatively charged and this result in a repulsion between nanoparticles eventually leading to a lesser extent of aggregation. Formation of a stable suspension was also observed in the presence of citric acid. These trends observed in aggregation pattern are of great environmental and biological importance as citric acid is abandon in the environment as well as in human body.

Les maladies neurodégénératives amyloïdes sont caractérisées par la dégénération et l'agrégation de protéines spécifiques. Ces processus d'agrégations restent mal compris par les spécialistes, et pour la plupart, hypothétiques seulement. Dans cette thèse, faîte en collaboration avec des biophysiciens, nous analysons ces méchanismes d'agrégations en nous basant sur des données expérimentales. Pour cela, la modélisation est une étape incontournable. Nous présentons deux modèles que nous confrontons aux expériences. Le premier modèle, connu de la littérature, est celui de Becker-Döring. Un système infini d'équations différentielles ordinaires. Ce premier modèle nous permet de reproduire se manière satisfaisante les premières étapes des expériences. Le second modèle que nous introduisons, se base sur une hypothèse réactionnelle additionnelle, formulée à partir des simulations du premier modèle, et qui consiste en la formation de fibres différentes. Ce deuxième modèle nous permet de mieux reproduire les expériences. / The amyloid neurodegenerative diseases are characterized by the degeneration and the aggregation of specific proteins. These aggregation processes remain misunderstood by specialists and, mostly, only hypothetical. In this thesis, and in collaboration with biophysicists, we analyze the mechanisms of aggregation, relying on experimental data. Modeling is then a must. We present two models which we compare with the experiments. The first model, well-known from the literature is the Becker-Döring system. An infinite system of ordinary differential equations. This first model allows us to reproduce satisfactorily the early stages of the experiments. The second model we introduce is based on an additional hypothesis which is about the formation of different fibers. This second model allows us to reproduce the experiments.

Protein pharmaceuticals is one of the fastest growing class of therapeutics today. However, they pose a lot of challenges in production lines due to their poor stability. Protein aggregation is one of the most common results of protein instability and is a risk factor regarding the quality of therapeutics. This master thesis at RISE focused on validating the techniques Dynamic Light Scattering (DLS) and multi angle DLS (MADLS) with respect to detection of aggregation. The model protein B-lactoglobulin was used to assess the robustness and accuracy of DLS. A comparison between two instruments from Malvern, Zetasizer Nano (2006) and Zetasizer Ultra (2018) was done with respect to DLS. It was determined that they were in many ways equivalent, but the newer model Ultra was favourable due to reduced noise and its ability to detect a lower concentration of aggregates. MADLS produced more precise results which is reflected in narrower distributions and has a higher sensitivity than DLS with regards to separating particles near in size. Both techniques proved sensitive enough to differentiate between aggregates and native protein. Experimental trials were performed with an active pharmaceutical ingredient, API. The experimental trials with the API aimed to investigate what conditions and surface-interfaces that might pose a risk for aggregation. Despite efforts put in creating an environment where aggregation could be monitored, aggregation could not be established. Measurements with the API generated less reliable results due to noisy data and a lack of reproducibility between individual measurements.

Les réseaux sans fils et mobiles se sont énormément développés au cours de ces dernières années. Loin d'être réservés aux pays industrialisés, ces réseaux nécessitant une infrastructure fixe limitée se sont aussi imposés dans les pays émergents et les pays en voie de développement. En effet, avec un investissement structurel relativement très faible en comparaison de celui nécessaire à l'implantation d'un réseau filaire, ces réseaux permettent aux opérateurs d'offrir une couverture du territoire très large, avec un coût d'accès au réseau (prix du téléphone et des communications) tout à fait acceptable pour les utilisateurs. Aussi, il n'est pas surprenant qu'aujourd'hui, dans la majorité des pays, le nombre de téléphones sans fil soit largement supérieur à celui des téléphones fixes. Ce grand nombre de terminaux disséminé sur l'ensemble de la planète est un réservoir inestimable d'information dont une infime partie seulement est aujourd'hui exploitée. En effet, en combinant la position d'un mobile et sa vitesse de déplacement, il devient possible d'en déduire la qualité des routes ou du trafic routier. Dans un autre registre, en intégrant un thermomètre et/ou un hygromètre dans chaque terminal, ce qui à grande échelle impliquerait un coût unitaire dérisoire, ces terminaux pourraient servir de relai pour une météo locale plus fiable. Dans ce contexte, l'objectif de cette thèse consiste à étudier et analyser les opportunités offertes par l'utilisation des données issues des terminaux mobiles, de proposer des solutions originales pour le traitement de ces grands masses de données, en insistant sur les optimisations (fusion, agrégation, etc.) pouvant être réalisées de manière intermédiaire dans le cadre de leur transport vers les(s) centre(s) de stockage et de traitement, et éventuellement d'identifier les données non disponibles aujourd'hui sur ces terminaux mais qui pourraient avoir un impact fort dans les années à venir. Un prototype présentant un exemple typique d'utilisation permettra de valider les différentes approches. / Mobile and wireless networks have developed enormously over the recent years. Far from being restricted to industrialized countries, these networks which require a limited fixed infrastructure, have also imposed in emerging countries and developing countries. Indeed, with a relatively low structural investment as compared to that required for the implementation of a wired network, these networks enable operators to offer a wide coverage of the territory with a network access cost (price of devices and communications) quite acceptable to users. Also, it is not surprising that today, in most countries, the number of wireless phones is much higher than landlines. This large number of terminals scattered across the planet is an invaluable reservoir of information that only a tiny fraction is exploited today. Indeed, by combining the mobile position and movement speed, it becomes possible to infer the quality of roads or road traffic. On another level, incorporating a thermometer and / or hygrometer in each terminal, which would involve a ridiculous large-scale unit cost, these terminals could serve as a relay for more reliable local weather. In this context, the objective of this thesis is to study and analyze the opportunities offered by the use of data from mobile devices to offer original solutions for the treatment of these big data, emphasizing on optimizations (fusion, aggregation, etc.) that can be performed as an intermediate when transferred to center(s) for storage and processing, and possibly identify data which are not available now on these terminals but could have a strong impact in the coming years. A prototype including a typical sample application will validate the different approaches.

Les tauopathies sont des maladies neurodégénératives caractérisées par l’agrégation de protéine Tau. Mis à part ce marqueur pathologique commun, les tauo-pathies présentent une grande diversité, tant sur le plan clinique qu’anatomo-pathologique, qui pourrait résulter de mécanismes pathologiques différents. Un mécanisme commun pourrait impliquer de petits agrégats de type oligomériques comme étant l’espèce toxique dans les tauopathies.L’objectif de ce projet est de déveloper plusieurs modèles de tauopathies, génétiques ou sporadiques, par transfer de gène de la protéine Tau humaine à l’aide de vecteurs adéno-associés. Trois vecteurs sont utilisés, chacun induisant un phénotype spécifique. Tout d’abord, la surexpression de hTAUWT induit une hyperphosphorylation de la protéine associée à une forte mort neuronale, mais en absence d’agrégation.Sa co-expression avec le peptide pro-agrégant TauRD-ΔK280 dans le groupe hTAUProAggr promeut son agrégation, ce qui est associé à des effets neuroprotecteurs. La construction hTAUP301L induit à la fois la formation d’agrégats solubles et matures, associée à un niveau intermédiaire de toxicité. Ces résultats supportent l’idée que les formes solubles oligomériques jouent un rôle crucial dans la pathologie associée à Tau.Ces modèles rapides, obtenus après expression de Tau à des niveaux similaires, récapitulent donc la variabilité phénotypique observée dans les tauopathies humaines. Ils devraient servir dans le futur pour étudier les mécanismes sous-tendant la toxicité des différentes espèces de Tau. Ils pourraient aussi être utiles pour étudier la spécificité et la sélectivité de composés développés pour l’imagerie de Tau par tomographie par émission de positon. / Tauopathies are neurodegenerative diseases characterized by the aggregation of Tau protein. Despite this common hallmark, tauopathies exhibit a wide variety of clinical and anatomo-pathological presentations, which may possibly result from different pathological mechanisms. One hypothesized common mechanism, however, implicates small oligomeric aggregates as drivers of Tau-induced toxicity.The aim of this project was to develop models of sporadic and genetic tauopathies, using adeno-associated viruses to mediate gene transfer of human Tau to the rat brain. Three different constructs were used, each giving rise to a specific phenotype. First, hTAUWT overexpression led to a strong hyperphosphorylation of the protein which was associated with neurotoxicity in absence of any significant aggregation. Its co-expression with the pro-aggregation peptide TauRD-ΔK280 in the hTAUProAggr group strongly promoted its aggregation, with neuroprotective effects. hTAUP301L construct led to aggregation into soluble species as well as mature aggregates accompanied with an intermediate toxicity. Those results support the hypothesis that soluble oligomeric species are key players of Tau-induced neurodegeneration.Those fast developing models, obtained through similar overexpression of human Tau, thus recapitulated the phenotypic variability observed in human tauopathies. Those should prove useful in the future to study mechanisms underlying the toxicity of various Tau species. Those could also serve to study the specificity and selectivity of Tau-directed tracers for positon emission tomography (PET) imaging.

<div>Reduction in the cost of Network Cameras along with a rise in connectivity enables entities all around the world to deploy vast arrays of camera networks. Network cameras offer real-time visual data that can be used for studying traffic patterns, emergency response, security, and other applications. Although many sources of Network Camera data are available, collecting the data remains difficult due to variations in programming interface and website structures. Previous solutions rely on manually parsing the target website, taking many hours to complete. We create a general and automated solution for indexing Network Camera data spread across thousands of uniquely structured webpages. We analyze heterogeneous webpage structures and identify common characteristics among 73 sample Network Camera websites (each website has multiple web pages). These characteristics are then used to build an automated camera discovery module that crawls and indexes Network Camera data. Our system successfully extracts 57,364 Network Cameras from 237,257 unique web pages. </div>

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第22155号 / 工博第4659号 / 新制||工||1727(附属図書館) / 京都大学大学院工学研究科高分子化学専攻 / (主査)教授 田中 一生, 教授 秋吉 一成, 教授 古賀 毅 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DGAM