Em todo o mundo é crescente o uso drogas de abuso sintéticas conhecidas com designer drugs. Os principais representantes desta classe são o Ecstasy ou 3,4-metilenodioximetanfetamina (MDMA) e o Eve ou 3,4-metilenodioxietilanfetamina (MDEA), substâncias com efeitos estimulantes e alucinógenos. No Brasil é crescente sua divulgação pela mídia e o uso recreacional tem sido constatado em vários pacientes que buscam tratamento nas clínicas para dependentes. O presente trabalho constitui validação de metodologia analítica para o diagnóstico laboratorial do uso de MDMA, MDEA e seu produto de biotransformação, o 3,4-metilenodioxianfetamina (MDA), em sangue total e urina, por cromatografia líquida de alta eficiência com detecção por fluorescência. Os métodos desenvolvidos mostraram boa linearidade, precisão, exatidão, rendimento e capacidade de detectar os analitos mesmos quando presentes em baixas concentrações, o que permite sua aplicação na verificação da intoxicação aguda quanto no uso recreacional destas drogas de abuso. / There is a worldwide increase in the use of the synthetic drugs of abuse known as designer drugs. The main representatives of this class are Ecstasy or 3,4-methylenodioxymethamphetamine (MDMA) and Eve or 3,4- methylenodioxyethylamphetamine (MDEA), substances with stimulant and hallucinogenic effects. In Brazil media coverage of them is on the increase and their recreational is in evidence by the growing numbers of patients who seek treatment at drug treatment centers. This paper validates the analytical methodology for the laboratory diagnosis of the use of MDMA, MDEA and their product of biotransformation, 3,4-methylenodioxyamphetamine (MDA), in whole blood and urine by high performance liquid chromatography with fluorescence. The developed methods showed good linearity, precision, accuracy, yield and capacity to detect analytes even when present in low concentrations, which enables its application in cases high intoxication as well as in cases of the recreational use of these drugs of abuse.

Orientador: Ary Fernandes Junior / Resumo: Espécies vegetais são fontes de moléculas biologicamente ativas que têm um importante papel no desenvolvimento de novos fármacos e, portanto, suas propriedades merecem ser investigadas. Apesar de serem espécies aromáticas e apresentarem um potencial farmacológico, algumas atividades biológicas dos óleos essenciais das folhas de Protium heptaphyllum, Hedyosmum brasiliense, Blepharocalyx salicifolius, Baccharis dracunculifolia e Nectandra megapotamica ainda não foram avaliadas. O objetivo deste trabalho foi verificar a ação citotóxica, antileishmania e antimicrobiana destes óleos essenciais com o intuito de estabelecer espécies vegetais com potencial uso na elaboração de fármacos ou como terapias complementares aos tratamentos convencionais de doenças de impacto em saúde pública. Os óleos essenciais foram obtidos por destilação de folhas frescas por arraste de vapor, a composição química determinada por análises de cromatografia gasosa/espectrometria de massas, as atividades biológicas testadas utilizando o método de microdiluição e a verificação dos mecanismos de morte celular feita por citometria de fluxo. B. salicifolius e B. dracunculifolia apresentaram elevado rendimento (0,86% e 0,89% respectivamente) quando comparado aos demais óleos essenciais avaliados. H. brasiliense e B. salicifolius apresentaram resultados promissores sobre linhagens tumorais Ehrlich (51,59 e 42,04 μg mL-1) e MDA-MB-231 (62,40 e 46,60 μg mL-1), com maior ação seletiva para estes tipos celulares se c... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: lant species are sources of biologically active molecules that play an important role in the development of new drugs, and therefore, their properties deserve to be investigated. In this regard, Protium heptaphyllum, Hedyosmum brasiliense, Blepharocalyx salicifolius, Baccharis dracunculifolia and Nectandra megapotamica are aromatic species with pharmacological potential, producing essential oils whose biological activities had not yet been investigated. The aim of this work was to assess any cytotoxic, antileishmania, or antimicrobial action of these essential oils to determine those plant species with potential in the elaboration of drugs or in complementary treatments of diseases with an impact on public health. Essential oils were obtained from fresh leaves by steam distillation. Chemical composition was determined by gas chromatography/mass spectrometry. Biological activities were assessed using the microdilution method while cell death was checked by flow cytometry. B. salicifolius and B. dracunculifolia presented high yields (0.86% and 0.89%, respectively) relative to the other species assessed. H. brasiliense and B. salicifolius showed promising action on Ehrlich (at 51.59 and 42.04 μg mL-1 concentration respectively) and MDA-MB-231 tumor lines (at 62.40 and 46.60 μg mL-1 concentration respectively), with less selective action against normal MCF-10A breast cells (at > 512 and 314.44 μg mL-1 concentration respectively). Flow cytometry results showed that B. salicifolius... (Complete abstract click electronic access below) / Doutor

Em todo o mundo é crescente o uso drogas de abuso sintéticas conhecidas com designer drugs. Os principais representantes desta classe são o Ecstasy ou 3,4-metilenodioximetanfetamina (MDMA) e o Eve ou 3,4-metilenodioxietilanfetamina (MDEA), substâncias com efeitos estimulantes e alucinógenos. No Brasil é crescente sua divulgação pela mídia e o uso recreacional tem sido constatado em vários pacientes que buscam tratamento nas clínicas para dependentes. O presente trabalho constitui validação de metodologia analítica para o diagnóstico laboratorial do uso de MDMA, MDEA e seu produto de biotransformação, o 3,4-metilenodioxianfetamina (MDA), em sangue total e urina, por cromatografia líquida de alta eficiência com detecção por fluorescência. Os métodos desenvolvidos mostraram boa linearidade, precisão, exatidão, rendimento e capacidade de detectar os analitos mesmos quando presentes em baixas concentrações, o que permite sua aplicação na verificação da intoxicação aguda quanto no uso recreacional destas drogas de abuso. / There is a worldwide increase in the use of the synthetic drugs of abuse known as designer drugs. The main representatives of this class are Ecstasy or 3,4-methylenodioxymethamphetamine (MDMA) and Eve or 3,4- methylenodioxyethylamphetamine (MDEA), substances with stimulant and hallucinogenic effects. In Brazil media coverage of them is on the increase and their recreational is in evidence by the growing numbers of patients who seek treatment at drug treatment centers. This paper validates the analytical methodology for the laboratory diagnosis of the use of MDMA, MDEA and their product of biotransformation, 3,4-methylenodioxyamphetamine (MDA), in whole blood and urine by high performance liquid chromatography with fluorescence. The developed methods showed good linearity, precision, accuracy, yield and capacity to detect analytes even when present in low concentrations, which enables its application in cases high intoxication as well as in cases of the recreational use of these drugs of abuse.

Thesis (M.A. (English Studies)) -- University of Limpopo, 2014 / This study discusses African identity as portrayed in Zakes Mda’s The Madonna of Excelsior (2002) and Bessie Head’s Maru (1971). It explores identity and its subcomponents within the South African context as asserted in these novels. Mda employs a retrospective communal voice that blends historical accounts with fiction in order to subvert and satirise apartheid nationalism. Head, on the other hand, constructs a positive image of feminine identity in the world characterised by tribalism, patriarchal system and stereotypical subjugation of women. She dismantles established racial and ethnic prejudice against minority groups and the underprivileged. The study applies a trilogy of theoretical framework to analyse and interpret selected data: Discourse Analysis, Text Analysis and Afrocentricity. It further examines a fluidity of identities in both social and political spheres and demonstrates how suppression of these identities affects individuals and nation states. It reveals that, as a microcosm of Africa, South Africa reflects atrocious injustices of the past, carried out in the form of colonisation and apartheid, bringing about a different kind of identity of the African people. These two novels take us back to the past so that we can understand the present and subsequently build Africa’s identity of the future. KEY CONCEPTS Afrocentricity; Identity; Discrimination; Miscegenation; Otherness; Hybridity; Animalistic Dehumanisation.

導引精靈(wizard)是一種用來收集用戶端資料的互動式使用者介面應用程式，常被廣泛的使用在軟體系統裡，也是大多數應用程式常見的功能之一。導引精靈的使用不僅簡化了複雜的資料收集過程，也可以避免資料的遺漏以確保收集資料的完整性；此外在資料收集的過程中導引精靈所提供的適當提示與即時資料驗證，還可以提高資料收集的正確性，所以導引精靈對於應用程式的資料收集是相當有用的。 本研究的目標是開發一個模型驅動的導引精靈開發系統，希望能在相同或不相同的時間裡快速建構多平台導引精靈程式。我們提出的系統稱為MoDWiz，它實現了應用「模型驅動架構(MDA)」於多平台導引精靈開發的所有工具支援。為了讓使用者建構自己的(平台無關)導引精靈模型，MoDWiz不僅提供了用以規範導引精靈的超模型，還制定一個特定領域語言WDL以作為此超模型的具體語法。此外，由於WDL的制定，我們得以提供專屬的編輯器以輔助使用者進行導引精靈模型的編輯。目前MoDWiz支援三種執行平台的導引精靈開發，分別為網頁應用程式、Eclipse與Java。而根據MDA理論，我們必須制定的三種平台超模型均已內含於MoDWiz。除此之外，MoDWiz的工具鏈還包括用來將平台無關導引精靈模型轉換成符合每一個特定平台導引精靈模型的M2M工具，以及將每一個特定平台導引精靈模型轉換成相對應實作的M2T工具。所有MoDWiz的工具與WDL編輯器程式均實作為Eclipse 外掛程式，因此能夠與Eclipse平台高度整合。當利用WDL編輯器完成導引精靈模型的製作之後，使用者只需透過簡單的滑鼠點擊就可以完成導引精靈程式的實作。 / A wizard is an interactive user interface program used to collect data from the user. It is widely used in software systems and is a common part of most applications. Not only does the use of wizards modularize and simplify complex data collection process, but it can also avoid data missing and ensure data integrity. Furthermore, during the process of data collection, since a wizard can provide tips and instant data validation it can also improve the correctness of collected data. As a conclusion, it is very beneficial to use wizards in an application. The goal of this research is the development of a model-driven wizard generation system (MoDWiz) that can be used to help rapid construction of multi-platform wizards to be developed at different or the same time. MoDWiz is our solution to the problem of applying OMG's model-driven architecture (MDA) to the development of multi-platform wizards. In order for the user to construct his (platform independent) wizard model, MoDWiz provides not only a wizard metamodel but also a domain specific language (DSL) called WDL as a concrete syntax of the metamodel. Owing to the availability of WDL, we are able to provide also a friendly editor to help the user to edit his wizard models. MoDWiz supports at present three platforms: eclipse platform, web application platform and plain Java platform. Accordingly metamodels of wizards for these platforms have to be defined and indeed have been provided in MoDWiz. Apart from these, MoDWiz's tool chain includes also M2M tools, which could transform every platform independent wizard model into a corresponding PSM model for each platform, as well as M2T tools, which could transform every platform specific wizard model into a corresponding implementation. All of MoDWiz's tools and wizard editor are implemented as eclipse plug-ins and thus are highly integrated with eclipse. As a result it is very easy to get a wizard implementation by simple mouse clicks once its model has been constructed using MoDWiz.

Ce travail de thèse, réalisé au sein de l'entreprise MONDECA et du laboratoire de recherche INSERM, est né du besoin de disposer d'un serveur capable de supporter le processus éditorial de Systèmes d'Organisation de Connaissances (SOC) et soulève la problématique suivante: comment harmoniser la représentation des SOC et de leurs correspondances afin de proposer des services unifiés qui supportent l'édition, la publication et l'utilisation efficaces des connaissances de ces référentiels? Pour répondre à cette problématique, nous soutenons la thèse que l'élaboration d'un modèle de représentation commune de SOC est une solution adaptée pour (i) pallier l'hétérogénéité de ces référentiels, (ii) favoriser l'interopérabilité sémantique au sein d'un Système d'Information et (iii) proposer des services unifiés quel que soit le SOC. Nous utilisons pour cela des méthodes propres à l'Ingénierie des Connaissances couplées à celles de l'Ingénierie des modèles. Les contributions présentées se concentrent sur trois axes. Dans un premier axe, nous souhaitons obtenir une solution de modélisation de SOC la plus générique possible et qui puisse être étendue pour prendre en compte les spécificités de chacun des référentiels. Nous proposons donc un modèle extensible commun de représentation, nommé UniMoKR, construit à partir des standards, recommandations et projets existants. Notre modèle a été proposé et intégré en partie dans la future norme ISO 25964 qui porte sur la représentation des terminologies. Nous avons également soumis deux patrons de modélisation d'ontologie au portail Ontology Design Pattern. Le second axe est consacré à la proposition de services unifiés qui reposent sur cette modélisation. Parmi ces services nous distinguons l'export de tout ou partie de SOC dans un format standard d'échange ou encore des services Web de gestion de terminologies. Pour mettre ces services à disposition, nous préconisons la méthode de transformation de modèles qui utilise le langage SPARQL pour l'expression des règles de transformation. Dans un troisième axe, nous présentons l'application de notre solution testée et commercialisée pour divers projets dans différents domaines d'applications. Nous montrons ici la faisabilité de notre approche, ainsi que l'amélioration que la représentation formelle de notre modèle apporte à la qualité des informations. Ces implémentations ont permis d'effectuer une validation en condition d'utilisation.

Avec l'émergence d'Internet et la prolifération de nouvelles technologies, la conception et le développement d'applications complexes doivent impérativement prendre en compte les standards et les aspects de répartition, déploiement et réutilisation de code. C'est la source d'une nouvelle problématique liée à la programmation. Un changement radical des méthodologies est nécessaire pour aisément prendre en compte ces différentes facettes. Cette thèse jette les bases d'une nouvelle manière de programmer où ces facettes ou intentions sont automatiquement intégrées aux spécifications ou modèles abstraits de l'application lors de phases de génération de code source. Cette nouvelle programmation est dit générative. Cette idée a été appliquée, à différents niveaux, lors de la réalisation d'une application, aussi bien pour la représentation de données ou d'environnements interactifs que pour les traitements sémantiques ou l'architecture. Ainsi le code final obtenu après génération s'appuie sur les technologies XML pour la représentation des données, les technologies objets et beans pour les vues et l'interface utilisateur, la programmation par aspect et le patron de conception visiteur pour les traitements sémantiques et la programmation par composants pour une architecture ouverte et une application répartie et déployable. Les principaux gains d'une telle programmation sont une meilleure qualité du logiciel due à la séparation de la logique métier et des spécificités technologiques, une simplification du code métier à écrire, l'ajout rapide de nouvelles facettes et un portage vers d'autres plates-formes ou technologies facilité.

<p>Lipid peroxidation is thought to be an important factor in the pathophysiology of a number of diseases and in the process of ageing, but its measurement <i>in vivo</i> has been difficult. The aim of this thesis was to evaluate methods for measurement of lipid peroxidation <i>in vivo</i> that are suitable for clinical investigations, and to apply these methods in animal and human studies investigating basal conditions and situations associated with increased lipid peroxidation.</p><p>The ferrous oxidation in xylenol orange assay for quantification of total plasma lipid hydroperoxides was re-evaluated regarding sample handling and storage. It was shown to be a useful tool for analyses of fresh but not stored plasma samples.</p><p>A methodology for measurement of the total amount (sum of free and esterified) of an F₂-isoprostane, 8-iso-prostaglandin F_2α, in tissues using alkaline hydrolysis in combination with an existing radioimmunoassay was developed. High levels of 8-iso-prostaglandin F_2α in rat liver tissue were quantified by this technique both at basal conditions and in an experimental model of increased lipid peroxidation induced by carbon tetrachloride.</p><p>Supplementation with vitamin E to rats decreased both non-enzymatic and enzymatic lipid peroxidation as measured by 8-iso-prostaglandin F_2α and a major prostaglandin F_2α metabolite. This was verified both in the urine at basal conditions, and in the urine and liver tissue after carbon tetrachloride induced lipid peroxidation.</p><p>In a randomised cross-over study in humans, a rapeseed oil-based diet with an increased proportion of easily oxidised polyunsaturated fatty acids was compared to a control diet rich in saturated fats. The rapeseed oil-based diet did not seem to increase the degree of lipid peroxidation in plasma and urine as measured by 8-iso-prostaglandin F_2α, hydroperoxides and malondialdehyde, presumably due to a sufficient content of antioxidants in the rapeseed oil diet.</p><p>In conclusion, the simultaneous measurement of several biomarkers of lipid peroxidation is a promising approach for future studies investigating the possible role of lipid peroxidation <i>in vivo</i> under basal conditions and in the pathology of diseases.</p>

Lipid peroxidation is thought to be an important factor in the pathophysiology of a number of diseases and in the process of ageing, but its measurement in vivo has been difficult. The aim of this thesis was to evaluate methods for measurement of lipid peroxidation in vivo that are suitable for clinical investigations, and to apply these methods in animal and human studies investigating basal conditions and situations associated with increased lipid peroxidation. The ferrous oxidation in xylenol orange assay for quantification of total plasma lipid hydroperoxides was re-evaluated regarding sample handling and storage. It was shown to be a useful tool for analyses of fresh but not stored plasma samples. A methodology for measurement of the total amount (sum of free and esterified) of an F2-isoprostane, 8-iso-prostaglandin F2α, in tissues using alkaline hydrolysis in combination with an existing radioimmunoassay was developed. High levels of 8-iso-prostaglandin F2α in rat liver tissue were quantified by this technique both at basal conditions and in an experimental model of increased lipid peroxidation induced by carbon tetrachloride. Supplementation with vitamin E to rats decreased both non-enzymatic and enzymatic lipid peroxidation as measured by 8-iso-prostaglandin F2α and a major prostaglandin F2α metabolite. This was verified both in the urine at basal conditions, and in the urine and liver tissue after carbon tetrachloride induced lipid peroxidation. In a randomised cross-over study in humans, a rapeseed oil-based diet with an increased proportion of easily oxidised polyunsaturated fatty acids was compared to a control diet rich in saturated fats. The rapeseed oil-based diet did not seem to increase the degree of lipid peroxidation in plasma and urine as measured by 8-iso-prostaglandin F2α, hydroperoxides and malondialdehyde, presumably due to a sufficient content of antioxidants in the rapeseed oil diet. In conclusion, the simultaneous measurement of several biomarkers of lipid peroxidation is a promising approach for future studies investigating the possible role of lipid peroxidation in vivo under basal conditions and in the pathology of diseases.

Ischemic brain injury causes neurodegeneration. In this study, the mechanism of neurodegeneration was investigated by examining the role of sterol regulatory element binding protein-1 (SREBP-1), CCAAT enhancer binding protein&amp / #946 / (C/EBP&amp / #946 / ), glutathione (GSH), malondialdehyde (MDA), glutathione-S-transferase (GST), and superoxide dismutase (SOD). Carotid artery occlusion (CAO) plus hypotension was produced for 10 minutes. Control groups were sham operated. Animals were sacrificed after 24 hours, 1 week, 2 and 4 weeks of reperfusion periods. The expression of C/EBP&amp / #946 / and SREBP-1 in rat brain cortex and cerebellum were examined by western blotting. C/EBP&amp / #946 / expressions significantly increased in both cytosolic (1.19, 1.58 fold) and nuclear (1.73, 1.81 fold) extracts of brain cortex at 24 hours and 1 week CAO groups, respectively. In cerebellum, C/EBP&amp / #946 / expression significantly increased in 1 week, cytosolic (1.63 fold), and nuclear (1.35 fold) extracts. SREBP-1 expression increased significantly in both cytosolic (2.07 fold) and nuclear (1.41 fold) extracts of brain cortex in 1 week. SREBP-1 expression significantly increased in cytosolic (2.15 fold) and nuclear (1.79 fold) extracts of cerebellum in 1 week. There were no significant alterations in SREBP-1 C/EBP&amp / #946 / expressions for 2 and 4 weeks in both cytosolic and nuclear extracts of brain cortex and cerebellum. There were insignificant changes in GSH and GST levels in cortex. However, MDA and SOD levels significantly increased by 43.0 % and 47.3 %, respectively, in 24 hours. Our findings indicate that increase in SREBP-1 and C/EBP&amp / #946 / expressions may be related to oxidative stress during ischemic neurodegenerative processes.