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Recherche et évaluation d'antalgiques originaux : les activateurs des canaux potassiques TREK-1Rodrigues, Nuno 02 December 2011 (has links)
Les antalgiques utilisés aujourd’hui sont des produits anciens et plusieurs d’entre eux datent du 19ème siècle. La morphine demeure l’antalgique de référence pour les douleurs dites par excès de nociception, mais elle est à l’origine d’effets indésirables gênants et graves. Il a été démontré que l’effet antalgique de la morphine passait par l’activation des canaux potassiques TREK-1. Les travaux de recherche ont donc comme objectif la recherche d’antalgiques originaux activateurs de TREK-1. Nous avons synthétisé des activateurs de TREK-1 décrits dans la littérature puis nous avons évalué leur activité antalgique in vivo (writhing test) ce qui nous a permis d’identifier le CDC comme molécule « lead ». Nous avons ensuite synthétisé 43 analogues du CDC que nous avons évalué pour leur effet antalgique ainsi que leur capacité à activer les canaux TREK-1 (électrophysiologie). Ces molécules ont été préparées en 3 à 12 étapes avec des rendements de 3 à 72 % en utilisant des réactions telles que : aldolisation, oléfination de Watsworth et Horner, Peterson, estérification …Des résultats très prometteurs ont émergé de cette étude de relation structure-activité avec 8 molécules qui se démarquent avec un très bon effet antalgique (>50% inhibition de la douleur) ainsi qu’une bonne activation des canaux TREK-1 (R>2). Enfin nous avons analysé les résultats de cette étude par modélisation moléculaire (QSAR) ce qui nous a permis d’identifier les caractéristiques structurales essentielles de ces molécules. / Analgesics used today are old products and several of them date from the 19th century. Morphine remains the analgesics of reference for pains called by excess of nociception, but it is at the origin of awkward and serious side effects. It was shown that the analgesic effect of morphine passed by the activation of potassium channels TREK-1. The objective of this work is thus to develop original analgesics, activators of TREK-1. We synthesized activators of TREK-1 described in the literature and we evaluated their analgesic activity in vivo (writhing test) which enabled us to identify CDC as a lead molecule. We then synthesized 43 analogues of CDC which we evaluated for their analgesic effect and their ability to activate TREK-1 channels (electrophysiology). These molecules were prepared in 3 to 12 steps with yields ranging from 3 to 72 % by using reactions such as : aldol reaction, Watsworth and Horner’s olefination, Peterson’s olefination, esterification … Very promising results emerged from this structure-activity relationship study with 8 molecules which display a very good analgesic effect (>50% inhibition of pain) as well as a good activation of TREK-1 channels (R> 2). Finally we analyzed the results of this study by molecular modeling (QSAR) which enabled us to identify the essential structural characteristics of these molecules.
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Avaliação em campo de três armadilhas automáticas para capturar mosquitos (Diptera:Culicidae) em área agrícola de Pariquera-Açu, São Paulo, Brasil / Field evaluation on three automatic traps to capture mosquitoes (Diptera:Culicidae) in agricultural area of Pariquera-Açu, São Paulo, Brazil.Ivy Luizi Rodrigues de Sá 14 August 2012 (has links)
Introdução: As diversas armadilhas apresentam rendimento diferenciado na captura, havendo a necessidade de buscar instrumentos que amostrem porções representativas das populações de mosquitos. Levanta-se a hipótese de que as armadilhas Mosquito Magnet Independence e CDC com CO2+Lurex3 sejam mais eficazes na captura de culicídeos do que a armadilha CDC luminosa. Objetivos: Avaliar a eficácia das armadilhas Mosquito Magnet Independence e CDC+CO2+Lurex3, em relação à CDC-luminosa, para a captura de culicídeos adultos em área agrícola na Fazenda Experimental em Pariquera-Açu, Vale do Ribeira, São Paulo, Brasil. Material e Métodos: Capturas mensais, das 15h00 às 21h00, por meio do delineamento em quadrado latino 3X3, no período de dezembro/2010 a novembro/2011. Perfis de diversidade de Rényi e índices de riqueza, dominância, diversidade, equabilidade e similaridade foram estimados para cada armadilha para compará-las. Resultados: Capturou-se 6.055 de 70 espécies e 12 gêneros. A CDC-luminosa amostrou 990 indivíduos de 42 espécies e 10 gêneros,a CDC+CO2+lurex31.419 indivíduos em 41 espécies e 10 gêneros e a Mosquito Magnet 3151 indivíduos de 46 espécies e 11 gêneros. A riqueza, pelo índice de Margalef e Perfil de Rényi, não apresentou diferença estatística para nenhuma armadilha no período dez/mai. A Mosquito Magnet obteve maior rendimento na mensuração da diversidade, segundos os índices de Shannon e Simpson, observados no perfil de Rényi. A dominância, pelo índice de Berger-Parker isolado,foi maior na Mosquito Magnet do que nas demais, nos dois períodos de capturas. O perfil de Rényi não apontou diferença significante para dominância. Índice de Pielou não mostrou significância em relação à CDC-luminosa para nenhuma das armadilhas nos dois períodos avaliados. Índices de Jaccard e Sorensen apontaram maior similaridade na composição de espécies entre a Mosquito Magnet e CDC+CO2+lurex3. Conclusões: A Mosquito Magnet Independence e CDC+CO2+Lurex3 apresentaram rendimento semelhante, nos meses mais frios e secos do ano. A utilização dessas armadilhas para a captura de determinados táxons pode ser importante ponto na estratégia de vigilância de espécies vetoras. Estudos com maior esforço amostral devem ser realizados para avaliar o rendimento das armadilhas Mosquito Magnet Independence e CDC+CO2 +lurex3 em áreas de ambiente alterado de Floresta Atlântica. / Introduction: The several traps have different performance in sampling mosquitoes,with the need to seek that capture representative portions of mosquito population. Formulate the hypothesis that the Mosquito Magnet trap and CDC+CO2+lurex3 are more effective in catching mosquitoes than the CDC light trap. Objectives: To evaluate the effectiveness the Mosquito Magnet Independence and CDC+CO2+lurex3 in relation to CDC light trap, to catching adult mosquitoes in the agricultural area at the Experimental Station in Pariquera-Açu, Vale do Ribeira, São Paulo, Brazil. Methods: Monthly captures, from 03:00pm-09:00pm, through the 3X3 Latin square from the December 2010 to November 2011. Rényi diversity profiles and indexes of the richness, dominance, diversity, evenness and similarity were estimated for each trap to compare them. Results: Were captured 6055 mosquitoes of the 70 species and 12 genera. CDC light traps sampled 990 specimens of 42 species and 10 genera, the CDC+CO2+lurex3 sampled 1419 specimens in 41 species and 10 genera and 3151 specimens were captured in the Mosquito Magnet belonging to 46 species and 11 genera. The richness, by the Margalef index on profile Rényi, showed no statistical difference for any trap in the period Dez/Mai. The Mosquito Magnet trap obtained higher yield in the measurement of diversity, according indexes of Shannon and Simpson, seen in profile Rényi. The dominance, by Berger-Parker index isolated, was higher in the Mosquito Magnet than in the other traps in both periods of captures. The profile Rényi showed no significant difference for dominance. Pielou index was not significant in relation to CDC light trap for any of the periods. Jaccard and Sorensen indexes showed greater similarity in composition of species between the CDC+CO2+lurex3 and Mosquito Magnet. Conclusions: The Mosquito Magnet Independence and CDC+CO2+ Lurex3 showed similar performance in colder and drier months of the year. The use of these traps to capture certain taxa can be important point in the surveillance approach vector species. Studies with greater sampling effort should be made to evaluate the performance of the Mosquito Magnet Independence and CDC+CO +lurex3 traps changed environment in areas of Atlantic Forest.
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O direito de arrependimento no comércio eletrônicoBruno, Fábio de Barros 21 September 2006 (has links)
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Previous issue date: 2006-09-21 / Article #49 of the Brazilian Consumer Bill of Rights (CDC Law 8.078/1990) establishes consumers right to return unwanted merchandise to suppliers within a period of 7 days for a full refund in the case of distance contracts. This law is intended to ensure consumers convenience and opportunity at the moment of purchase, compensate for consumers lack of familiarity with the product or service purchased, and protect consumers against particularly aggressive marketing practices. However, although the literal interpretation of this law specifies a 7-day refund period and contracts celebrated at distance for the exercise of this right, jurisprudence and judicial doctrine have not yet determined the exact boundaries under which consumers may return unwanted products. In other words, any product or service purchased from a supplier at distance may be returned within a 7-day period no-questions-asked. In any case, in e-commerce dealings the unrestricted exercise of this right can lead to significant losses on part of the suppliers. But, far from ignoring consumers rights suppliers often underscore them, though the actual scope and applicability of these rights remain to be clearly established. If consumers rights to return unwanted merchandise are exercised within the principles informing the legal system, they will eventually become a means of harmonizing e-commerce relations and, consequently, of encouraging participation in worldwide computer networks. / O direito de arrependimento é a prerrogativa instituída pelo art. 49 do Código de Defesa do Consumidor mediante a qual é facultado ao consumidor desistir, no prazo de sete dias e sem qualquer ônus, do contrato que tenha efetuado fora do estabelecimento comercial do fornecedor. Esta prerrogativa do consumidor tem por objetivo básico garantir a conveniência e oportunidade no ato de consumo, tanto suprindo a falta de contato prévio do consumidor com o produto ou serviço que adquire fora do estabelecimento do fornecedor, como coibindo as práticas comerciais eivadas de marketing agressivo. De acordo com uma interpretação gramatical desse artigo, em um primeiro momento, salvo o lugar onde se firmou o contrato e o prazo de reflexão, aparentemente pouco tem sido dito pela doutrina em relação a qualquer outro limite para que o consumidor exerça o direito em foco. Em suma, basta que o produto ou serviço tenha sido contratado fora do estabelecimento comercial e que a manifestação da desistência ocorra dentro no prazo de reflexão, para que ele seja exercido. Tal fato leva alguns doutrinadores a buscar interpretações que negam quase que totalmente a aplicação do direito de arrependimento ao comércio eletrônico, uma vez que sua aplicação irrestrita pode ser bastante prejudicial, sobretudo, ao empresário. O caminho no comércio eletrônico, no entanto, não é negar esse direito ao consumidor, mas sim, despertá-lo para a sua existência. Os limites de sua aplicabilidade, todavia, devem ser traçados a fim de se estabelecerem regras claras para os participantes da relação de consumo. Logo, uma interpretação mais adequada desse instituto se faz necessária à luz do comércio eletrônico; interpretação que possibilite não só um ponto de equilíbrio na aplicabilidade do direito de arrependimento fundamentado no próprio sistema jurídico, mas que também desperte a atenção dos consumidores para o seu exercício. É necessário o equilíbrio. Isto é, não negá-lo, mas acordar a sociedade para o seu uso; não para seu emprego desregrado e ilimitado, mas para o seu uso dentro dos princípios que regem o sistema, como meio de harmonização das relações de consumo no comércio eletrônico e, por conseqüência, como instrumento para a ampliação do número de pessoas incluídas na rede mundial de computadores.
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Nitrogen doped carbide derived carbon aerogels by chlorine etching of a SiCN aerogelZera, E., Nickel, W., Hao, G. P., Vanzetti, L., Kaskel, Stefan, Sorarù, G. D. 24 July 2017 (has links) (PDF)
Silicon was selectively removed from a silicon carbonitride (SiCN) aerogel by hot chlorine gas treatment, leading to a N-doped carbon aerogel (N-CDC aerogel). The combined effects of pyrolysis and etching temperature were studied with regard to the change in the composition of the material after etching as well as the microstructure of the produced hierarchically porous material. Upon removal of Si from amorphous SiCN, carbon and nitrogen, which are not bonded together in the starting material, react, creating new C–N bonds. The removal of silicon also gives rise to a high amount of micropores and hence a high specific surface area, which can be beneficial for the functionality of the carbonaceous material produced. The mesoporous structure of the aerogel allows us to complete the etching at low temperature, which was found to be a crucial parameter to maintain a high amount of nitrogen in the material. The combination of a high amount of micropores and the mesopore transport system is beneficial for adsorption processes due to the combination of a high amount of adsorption sites and effective transport properties of the material. The N-CDC aerogels were characterized by nitrogen physisorption, X-ray photoelectron spectroscopy (XPS), thermogravimetry (TG/DTA), and infrared spectroscopy (DRIFT) and they were evaluated as CO2 absorbers and as electrodes for electric double-layer capacitors (EDLCs).
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Nitrogen doped carbide derived carbon aerogels by chlorine etching of a SiCN aerogelZera, E., Nickel, W., Hao, G. P., Vanzetti, L., Kaskel, Stefan, Sorarù, G. D. 24 July 2017 (has links)
Silicon was selectively removed from a silicon carbonitride (SiCN) aerogel by hot chlorine gas treatment, leading to a N-doped carbon aerogel (N-CDC aerogel). The combined effects of pyrolysis and etching temperature were studied with regard to the change in the composition of the material after etching as well as the microstructure of the produced hierarchically porous material. Upon removal of Si from amorphous SiCN, carbon and nitrogen, which are not bonded together in the starting material, react, creating new C–N bonds. The removal of silicon also gives rise to a high amount of micropores and hence a high specific surface area, which can be beneficial for the functionality of the carbonaceous material produced. The mesoporous structure of the aerogel allows us to complete the etching at low temperature, which was found to be a crucial parameter to maintain a high amount of nitrogen in the material. The combination of a high amount of micropores and the mesopore transport system is beneficial for adsorption processes due to the combination of a high amount of adsorption sites and effective transport properties of the material. The N-CDC aerogels were characterized by nitrogen physisorption, X-ray photoelectron spectroscopy (XPS), thermogravimetry (TG/DTA), and infrared spectroscopy (DRIFT) and they were evaluated as CO2 absorbers and as electrodes for electric double-layer capacitors (EDLCs).
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Vibrační generátor pro zkoušky elektroniky / Recoil forces measurement after shotaVibration Test StandRozum, Stanislav January 2017 (has links)
The thesis describes design and construction of vibration generator driver. The device is controlled via standard Ethernet interface and allows user to change parameters of generated function in PC application which reads and evaluates frequency and amplitude from real-time measured data while the test is running. In the introduction, vibration tests and choice of generators and power amplifiers are described. Next part is focused on every aspect of the hardware design. Last two chapters implement firmware for all three microcontrollers and software for PC application.
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Evolution of porosity in carbide-derived carbon aerogelsOschatz, M., Nickel, W., Thommes, M., Cychosz, K. A., Leistner, M., Adam, M., Mondin, G., Strubel, P., Borchardt, L., Kaskel, S. 19 December 2019 (has links)
Carbide-derived carbon (CDC) aerogel monoliths with very high porosity are synthesized starting from polymeric precursors. Cross-linking by platinum-catalyzed hydrosilylation of polycarbosilanes followed by supercritical drying yields preceramic aerogels. After ceramic conversion and silicon extraction in hot chlorine gas, hierarchically porous carbon materials with specific surface areas as high as 2122 m² g⁻¹ and outstanding total pore volumes close to 9 cm³ g⁻¹ are obtained. Their pore structure is controllable by the applied synthesis temperature as shown by combined nitrogen (-196 °C) and carbon dioxide (0 °C) measurements coupled with electron microscopic methods. The combination of large micropore volumes and the aerogel-type pore system leads to advanced adsorption properties due to a combination of large storage capacities and effective materials transport in comparison with purely microporous reference materials as shown by thermal response measurements.
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The Evolution of Urban Community Development Corporations in Response to Contemporary Challenges and OpportunitiesBancroft, Sharon L. 01 January 2006 (has links)
Community development corporations (CDCs) have become important vehicles for revitalizing urban neighborhoods. These small, multi-disciplinary groups must adapt quickly to changing conditions in the industry. The author interviewed CDC directors and other industry experts from Richmond, Virginia and Atlanta, Georgia to identify and compare contemporary challenges, opportunities and adaptations among community developers. The cost and availability of land, inadequate funding and organizational capacity were significant barriers in both cities. In Richmond, increasing competition, NIMBY and staff retention were other barriers. In Atlanta, securing community buy-in, the permitting process, and the growing need for affordable housing were other barriers. Increasing public interest in affordable housing, the need for new housing types and increased housing demand present new opportunities. Atlanta also has new public policies supporting housing. In response, CDCs in both cities are expanding their geographic areas, developing partnerships, and adding new development products. Atlanta CDCs also reported expanding non-development activities.
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Functions of the Cdc14-Family Phosphatase Clp1p in the Cell Cycle Regulation of <em>Schizosaccharomyces pombe</em>: A DissertationTrautmann, Susanne 20 May 2005 (has links)
In order to generate healthy daughter cells, nuclear division and cytokinesis need to be coordinated. Premature division of the cytoplasm in the absence of chromosome segregation or nuclear proliferation without cytokinesis might lead to aneuploidy and cancer.
The cyclin dependent kinases, CDKs, are a main regulator of the cell cycle. Timely increase and decrease in their activity is required for cell cycle progression. To enter mitosis, mitotic CDK activity needs to rise. CDK activity stays elevated until chromosome segregation is completed and exit from mitosis requires decrease in CDK activity.
Observations in several experimental systems suggest that coordination of cytokinesis with the nuclear cycle is regulated through CDK activity. Prolonged high CDK activity, as it occurs when chromosome segregation is delayed, was found to oppose cytokinesis. Prevention of cytokinesis through high CDK activity may therefore provide a mechanism to prevent precocious cell division in the absence of chromosome segregation. To prevent polyploidy when cell division is delayed, progression through the next nuclear cycle should be inhibited until cytokinesis is completed, presumably by the inhibition of CDK activity.
In the fission yeast Schizosaccharomyces pombe, a signaling cascade called Septation Initiation Network (SIN) is required for the coordination of cytokinesis with the nuclear cycle. The SIN is essential for cytokinesis, triggering the execution of cell division through constriction of the actomyosin ring. The activation of the SIN signaling cascade, and thus cytokinesis, is opposed by high CDK activity, preventing precocious cytokinesis.
S. pombe delay entry into the next nuclear division in response to delayed cytokinesis due to defects in the contractile ring until cytokinesis is completed thereby preventing the accumulation of multinucleate, non viable cells. This safeguard against multinucleate cells is termed the cytokinesis checkpoint. The cytokinesis checkpoint keeps CDK activity low, preventing nuclear cycle progression. The SIN is required for the cytokinesis checkpoint and therefore is a key coordinator between nuclear cycle and cytokinesis. How the SIN functions in the cytokinesis checkpoint was not known.
Cdc14-family phosphatases are highly conserved from yeast to humans, but were only characterized in Saccharomyces cerevisiae at the time this thesis was initiated. Cdc14 had been identified as the effector of a signaling cascade homologous to the SIN, called the mitotic exit network (MEN), which is required for exit from mitosis. This thesis describes the identification of the S. pombe Cdc14-like phosphatase Clp1p as a component of the cytokinesis checkpoint. Clp1p opposes CDK activity, and Clp1p and the SIN activate each other in a positive feedback loop. This maintains an active cytokinesis checkpoint and delays mitotic entry. We further found that Clp1p regulates chromosome segregation.
Concluding, this thesis describes discoveries adding to the characterization of the cytokinesis checkpoint and the function of Clp1p. While others found that Cdc14-family phosphatases, including Clp1p, have similar catalytic functions, we show that their biological function may be quite different between organisms, possibly due to different biological challenges.
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Aplicação das normas do CDC aos contratos interempresariais: a disciplina das cláusulas abusivas / Application of the CDC rules to inter-business contracts: the discipline of abusive clausesFava, Marina Dubois 07 June 2010 (has links)
O presente estudo tem por objetivo demonstrar a necessidade de se tutelar a desigualdade substancial existente nas relações contratuais celebradas entre empresários, quando uma das partes, ainda que profissional, encontrar-se em situação de dependência econômica, favorecendo o abuso da parte contrária na situação concreta. O cerne do trabalho gira em torno do problema das cláusulas abusivas no âmbito dos contratos interempresariais. Busca-se demonstrar que, nas hipóteses em que não for possível repreendê-las por meio da aplicação do Código Civil ou da Lei Antitruste, seria possível equiparar o contratante vulnerável, sujeito a um abuso por parte de seu parceiro contratual, aos consumidores, para fins de aplicação dos dispositivos do Código de Defesa do Consumidor CDC ao contrato em questão. Para tanto, são analisados os conceitos de empresário, de consumidor tendo em vista as três principais correntes doutrinárias existentes no ordenamento pátrio e de dependência econômica. Especificamente em relação à definição de consumidor, tenta-se demonstrar que, nos dias de hoje, a Teoria Finalista Aprofundada parece ser a que melhor atende à necessidade de se buscar a solução mais justa no caso concreto, sem, contudo, banalizar a aplicação do CDC. Por fim, faz-se uma análise da jurisprudência brasileira sobre o tema, com o objetivo de delimitar os critérios para a incidência do CDC em contratos interempresariais, bem como os principais casos em que o conceito de consumidor-equiparado tem prevalecido nos litígios decorrentes de tais contratos. / The objective of the present study is to demonstrate the need of instructing the substantial inequality existing in contractual relations signed between businessmen, when one of the parties, although still professional, finds itself in a situation of economic dependence, favoring the abuse of the counterpart in the real situation. The core of this work involves the problem regarding abusive clauses in the scope of inter-business contracts. It seeks to demonstrate that, in hypothesis where it is not possible to reprehend them by means of application of the Civil Code or Antitrust Act, it would be possible to match the vulnerable contracting party, subject to an abuse by its contractual partner, to the consumers, for purposes of application of the provisions in the Consumer Defense Code CDC to the contract in question. To do so, it analyzes the concepts of businessman and consumers considering the three main doctrinaire schools of thought existing in the country system and economic dependence. Specially in relation to the definition of consumers, it attempts to demonstrate that, nowadays, the In-depth Finalist Theory seems to be the best theory that meets the need of searching for the more righteous solution in the real case, without, however, trivializing the application of the CDC. At last, an analysis of Brazilian jurisprudence is made on the subject, aiming to delimitate the criteria for the incidence of CDC in inter-business contracts as well as the main cases in which the concept of consumer has prevailed in such contracts for one of the parties.
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