Afin de s'adapter à son environnement chimique, l'organisme a développé au cours de l'évolution des systèmes enzymatiques capables de transformer de nombreuses molécules étrangères ou xénobiotiques (médicaments, composés toxiques, carcinogènes...), le plus souvent de nature hydrophobe, en métabolites suffisamment hydrophiles pour être plus facilement excrétés par voie urinaire et/ou biliaire. Certaines de ces enzymes sont également impliquées dans des processus cataboliques ou de biosynthèses de composés endogènes (acides gras, rétinoïdes, stéroïdes, prostaglandines…). Ces enzymes jouent ainsi un rôle fondamental à la fois dans la défense de l'organisme face à son environnement chimique et dans des processus physiologiques essentiels. On comprend dès lors que s'il existe, chez certains individus, des anomalies de séquence ou de structure des gènes codant pour ces enzymes, une partie de la population présentera une susceptibilité particulière à certaines molécules de l'environnement, voire des dysfonctionnements de certaines réactions biologiques indispensables. Les travaux de cette thèse s'inscrivent dans cette démarche. Dans un premier temps, ils ont consisté à évaluer la nature et l'étendue de la variabilité de la séquence nucléotidique de trois gènes codants pour les enzymes CYP4A11, CYP4A22 et la Glycine N-acyltransférase (GLYAT). Dans un deuxième temps, les analyses fonctionnelles des variations de séquence identifiées ont été abordées par des approches in silico et in vitro. Les cytochromes P450 CYP4A11 et CYP4A22, participent à la biotransformation de composés endogènes et sont impliqués plus particulièrement dans la voie d’activation de l’acide arachidonique. Des travaux récents suggèrent que des anomalies génétiques de ces enzymes constituent des facteurs de susceptibilité à l’hypertension artérielle chez l’homme. Nous avons ainsi analysé les variations de séquence du gène CYP4A11 et CYP4A22 dans des échantillons d'ADN provenant de volontaires sains. Au total, 26 polymorphismes ont été identifiés et 5 nouveaux CYP4A* allèles ont été caractérisés pour chaque isoforme CYP4A. Les structures 3D des protéines CYP4A ont été construites et validées pour l’analyse de l’impact des mutations identifiées. Bien que des travaux supplémentaires soient nécessaires pour confirmer le lien entre le polymorphisme génétique du CYP4A11 et du CYP4A22 et l’hypertension artérielle, ce travail représente la première description et caractérisation du polymorphisme génétique des isoformes CYP4A dans une population Française. De plus, nous avons mise en évidence une variabilité interethnique de ce polymorphisme génétique dans différentes populations testées. La glycine N-acyltransférase ou GLYAT est une enzyme impliquée dans la détoxication de xénobiotiques contenant un groupement carboxylique par conjugaison d’un résidu de glycine. Sept variations de séquence de la GLYAT ont été identifiées et quatre nouveaux GLYAT* allèles ont été caractérisés. La localisation des certaines mutations dans des structures secondaires très conservées de la protéine suggère un impact sur l’activité catalytique de cette enzyme. Bien que les conséquences cliniques potentielles de ces variations restent encore à étudier, ces résultats seront utiles pour de futures études d’association de ce polymorphisme génétique de la GLYAT avec les altérations de détoxications de xénobiotiques contenant un groupement carboxylique comme l’aspirine, certains pesticides ou le toluène. / Through evolution, in order to adapt to its chemical environment, the human organism has developed enzymatic systems that can transform exogenous molecules or xenobiotic (drugs, toxins, carcinogens…), generally of hydrophobic nature, in metabolites more easily excretable via urinary or biliary tract. Some of these enzymes are also involved in catabolic processes or in the biosynthesis of endogenous compounds (fatty acids, retinoids, steroids, prostaglandins…). These enzymes thus play a major role in the protective response of the body toward chemicals and in essential physiological processes. The existence of anomalies in the sequence or structure of the genes encoding these enzymes can expose carriers of these anomalies to particular susceptibility toward xenobiotics or to impairment of essential biological reactions. In a first step, we investigated the nature and extent of the sequence variability of three genes coding for the enzymes CYP4A11, CYP4A22 and Glycine N-acyltransferase (GLYAT). In a second step, functional analyses of sequence variations were carried out, by in silico and in vitro experiments. The CYP4A11 and CYP4A22 genes are the only members of the human CYP4A subfamily. The activity of the recently identified CYP4A22 isoform is still unknown, but the CYP4A11 isoform is know as a ω-hydroxylase of the arachidonic acid, which converted into 20-hydroxyeicosatetraenoic acid (20-HETE). Several studies have shown that genetic anomalies of CYP4A are likely to contribute for susceptibility to hypertension in humans. We analyzed the sequence variations of the CYP4A11 and CYP4A22 genes in genomic DNA samples of healthy volunteers. A total of 26 polymorphisms were identified and 5 novel CYP4A* alleles were characterized for each CYP4A gene. The CYP4A 3D models were built and validated to analyse the potential impact of sequence variations identified. This work represents the first description and characterisation of genetic polymorphism of the human CYP4A genes in a French population. The glycine N-acyltranferase or GLYAT plays an important role in the detoxification of xenobiotics containing a carboxylic group via conjugation with a glycine residue. Seven sequence variations of the GLYAT gene were identified and four novel GLYAT* alleles were characterized. Localisation of missense mutations in predicted secondary structures suggest that these variants might have a potential role on the GLYAT protein activity. These results could be helpful in investigating the potential association of GLYAT variants with an incidence of reduced efficiency in xenobiotic carboxylic acids detoxification in humans, such as acetylsalicylic acid, pesticides, and solvents (Toluene).

Submitted by Alexandra Feitosa (alexandra.feitosa@ufpe.br) on 2017-08-03T13:30:10Z No. of bitstreams: 1 2012-dissertação-AntonioCabralCarvalhoJunior.pdf: 1339364 bytes, checksum: 27ce703fb5c5c994f4eb45c94a9454cd (MD5) / Made available in DSpace on 2017-08-03T13:30:10Z (GMT). No. of bitstreams: 1 2012-dissertação-AntonioCabralCarvalhoJunior.pdf: 1339364 bytes, checksum: 27ce703fb5c5c994f4eb45c94a9454cd (MD5) Previous issue date: 2012-12-11 / O objetivo deste estudo exploratório é abordar o tema Consórcio Público, considerando o período posterior àentrada em vigor da Lei n.11.107/2005, que veio trazer para o federalismo, em sua face cooperativa, um instrumento normativo que disciplina a atuação consorciada. Apresenta-se um estudo bibliográfico, concentrando-se informações atinentes ao tema objeto do estudo, ainda incipientes e esparsas, pelo fato de a referida lei ser relativamente recente. Busca-se trazer: um aprofundamento de conceitos; uma apreciação do histórico do federalismo cooperativo no Brasil e da atuação associada, enfocando-se também as experiências de outros três países; uma abordagem regional, considerando o consórcio público como instrumento propulsor do seu desenvolvimento; uma apreciação acerca das inovações trazidas com a mencionada lei. Foram consultados livros, publicações, legislação e textos disponíveis na internet, recorrendo-se a autores que discorrem de forma densa sobre consórcios públicos, Federalismo Cooperativo, Descentralização e Análise da Região Nordeste. As inovações trazidas com a referida lei e com o Decreto Federal n.6.017/2007, que veio regulamentá-la, os ditames da Constituição Federal, da Lei de Responsabilidade Fiscal, dentre outros importantes diplomas normativos, são analisados no que diz respeito aos consórcios públicos, considerando-se os aspectos de interesse da Gestão Pública, na busca do entendimento da matéria sob o ponto de vista da Gestão e da atividade de Controle. Apesquisa de campo teve como fito diagnosticar o processo de estruturação dos consórcios intermunicipais no Estado de Pernambuco à luz da referida lei. Para tanto, aplicaram-se questionários, considerando-se as percepções de representantes municipais acerca da atuação consorciada. Em que peseo arcabouço legal mencionadoe o número significativo de Municípios que constam como vinculados a algum consórcio público, observa-se, no âmbito do Estado de Pernambuco, a ocorrência de diversos problemas relacionados, notadamente, a: dificuldades de coordenação, considerando o excessivo número de entes federados vinculados a alguns dos consórcios; inobservância às normas e aos aspectos formais; imprecisão na definição e no dimensionamento do alcance dos objetivos específicos; insuficiência de recursos financeiros. Ao final, apresentam-se propostas visando contribuir com o fomento à disseminação de consórcios públicos intermunicipais efetivos e sugestões de aspectos instigantes para pesquisas futuras em relação ao tema. / The objective of this exploratory study is to address the theme Public Consortium, considering the period after the entry into force of Law No. 11.107/2005, which brought to federalism on his corporative face, a legislative instrument that disciplines the actuation in consortium. A bibliographic study is presented, focusing the pertaining informations to the theme of study, still incipients and sparses, because that law is relatively recent. Seeks to bring: a deepening of concepts, an appreciation of the history of cooperative federalism in Brazil and the associated actuation, also focusing on the experiences of three other countries, a regional approach, considering the Public Consortium as an instrument that provides its development; an appreciation of the innovations brought by that law. Books, publications, legislation and texts available on the Internet were consulted using up the authors who talks in a dense way on Public Consortium, Cooperative Federalism, Decentralisation and Analysis of the Northeast. The innovations brought by that law, and by the Federal Decree N. 6.017/2007, which came regulate it, the dictates of the Federal Constitution, of the Fiscal Responsibility Law, among other important normative acts are analyzed in relation to Public Consortia, considering the aspects of interest of Public Management, in seeking to understand the subject from the point of view of the Management and Activity of Control. While the field research aimed to diagnose the structuring process of Intermunicipal Consortium in the State of Pernambuco based on that law. To this end, questionnaires were applied, considering the perceptions of municipal representatives on the consortium activities. Despite the set of rules mentioned, andthe significant number of municipalities listed as linked to some Public Consortium, is observed within the State of Pernambuco, the occurrence of several problems related notably to the: coordination difficulties, considering the excessive number of federal entities linked to some consortiums; disregard the rules and formal aspects; vagueness in defining and sizing of range of specific objectives; insufficient financial resources. At the end, proposals are presented aiming to contribute to fostering the dissemination of effective Intermunicipal Public Consortium and suggestions of exciting aspects for future research on the topic.

O gênero Croton possui aproximadamente 1300 espécies amplamente distribuídas em zonas tropicais e subtropicais do novo e velho mundo e é o segundo maior gênero de Euphorbiaceae. No presente trabalho, foram analisadas a composição e a morfologia das ceras foliares cuticulares de 13 espécies de Croton. Para a maioria das espécies, foram amostrados três indivíduos. A morfologia das ceras foi analisada por microscopia eletrônica de varredura. Diversos tipos de depósitos cerosos foram observados (amorfos, plaquetas, grânulos), principalmente na face adaxial e caracterizando grupos de espécies. A observação dos padrões de depósitos cerosos de várias espécies foi prejudicada na face abaxial, devido à alta densidade de tricomas. As ceras foram extraídas por três imersões consecutivas das folhas em diclorometano e a separação das classes dos constituintes foi feita por cromatografia em camada delgada preparativa. A análise da distribuição dos constituintes foi realizada por cromatografia a gás acoplada a espectrometria de massas. n-Alcanos e álcoois primários foram detectados em todos os indivíduos analisados. Triterpenos também são muito comuns, não tendo sido detectados em apenas uma espécie. Os esteroides são constituintes raros nas espécies analisadas. Os resultados da distribuição de n-alcanos, álcoois primários e triterpenos foram utilizados para o estabelecimento de afinidades químicas por meio de análises de agrupamento pelo método UPGMA, empregando-se distâncias euclidianas (n-alcanos e álcoois) e coeficiente de DICE (triterpenos), baseando-se na distribuição de cada classe de constituinte isoladamente e combinando-se as distribuições de n-alcanos e álcoois primários. Não se notou congruência entre as topologias dos dendrogramas de afinidades químicas e a filogenia molecular do gênero. Observou-se coerência entre algumas afinidades químicas e características morfológicas, como tipos de tricomas foliares e presença de glândulas peciolares. A distribuição de n-alcanos, álcoois primários e triterpenos mostraram-se úteis como caracteres da maioria das espécies analisadas. Entre os constituintes analisados, distribuição de álcoois primários revelou-se o melhor marcador para a caracterização de espécies. A variação intraespecífica, no entanto, impede que esses caracteres sejam úteis como marcadores taxonômicos de algumas espécies de Croton / Croton comprises nearly 1300 species distributed in tropical and subtropical areas of either the New or Old Worlds, making up the largest genus of Euphorbiaceae. In the present work, the chemical composition and the morphology of the foliar cuticular waxes of 13 species of Croton were analized. Three individuals were sampled for analyses of most species. The morphology of the waxes was analyzed by scanning electron microscopy. Several types of wax deposits were observed (amorph, platlets, granules), chiefly on the adaxial side, characterizing groups of species. The observation of wax deposits on the abaxial side was hampered in several species due to the high density of trichomes. The cuticular wax was extracted by three successive immersions of the leaves in dichloromethane, and the separation of the constituent classes was achieved by preparative thin layer chromatography. The analyses of the distribution of the constituents were performed by gas chromatography coupled to mass spectrometry. n-Alkanes and primary alcohols were detected in all analyzed individuals. Triterpenes were also very common, having not been detected in only one species. Steroids are rare constituents in the analyzed species. The results of the distribution of n-alkanes, primary alcohols and triterpenes were used for the establishment of chemical affinities using cluster analysis by the UPGMA method and Euclidean distances (n-alkanes and alcohols) and DICE coefficient, based on the distribution of each constituent class alone and combining the distribution of n-alkanes and primary alcohols. No congruence was noted between the topologies of the dendrograms of chemical affinity and the molecular phylogeny of the genus. Coherence was observed between chemical affinities and morphologic characteristics, such as types of foliar trichomes and petiolar glands. The distribution of n-alkanes, primary alcohols and triterpenes were shown to be useful as characters for most analyzed species. Among the constituents analyzed, the distribution of primary alcohols was the best marker for species characterization. Intraspecific variation, however, precludes the use of these characters as taxonomic markers of some Croton species

Thesis (MSc. (Chemistry)) -- University of Limpopo, 2016 / 2-Benzenesulfonyloxyquinoxaline was prepared following literature procedure followed by palladium-catalysed Negishi coupling reactions to yield the corresponding, 2-mono-substituted quinoxaline derivatives, 2-phenylquinoxaline and 2-butylquinoxaline. These Negishi cross-coupled derivatives were treated with various nucleophiles, in tetrahydrofuran at room temperature, to yield a series of di-substituted quinoxaline derivatives containing; aryl-, heteroaryl-, arylalkynyl- and alkyl-substituents. Tri-substitution was successful with reaction of 6-chloro-2-benzenesulfonyloxyquinoxaline with excess phenyl-magnesium bromide to yield 2,3,6-triphenylquinoxaline. Sonogashira cross-coupled compounds were successfully synthesised by reacting 2-benzenesulfonyloxyquinoxaline, 6-nitro-2-benzenesulfonyloxyquinoxaline and 6-chloro-2-benzenesulfonyloxyquinoxaline using phenylacetylene, respectively. Nucleophilic substitution was only successful on 2-(2-phenylethynyl)quinoxaline to yield 3-butyl-2-(2-phenylethynyl)quinoxaline. The formation of carbon-nitrogen bonds was accomplished via palladium-catalysed Buchwald-Hartwig amination of 2-benzenesulfonyloxyquinoxaline with arylamines to afford N-phenylquinoxalin-2-amine and N-benzylquinoxalin-2-amine in good to high yields. N-phenylquinoxalin-2-amine was subsequently treated with iodomethane to synthesise N-methyl-N-phenylquinoxalin-2-amine. Nucleophilic substitution on Buchwald-Hartwig coupled compounds was only successful when using alkyl nucleophiles. The reaction of all these quinoxaline derivatives with various nucleophiles does not stop at the stage of α-adduct formation, but continues with the oxidation of these compounds to aromatic substitution products. All synthesised compounds were characterised by NMR, and mass spectral data as well as melting points where applicable. N-Methyl-N-phenylquinoxalin-2-amine and 2,3,6-triphenylquinoxaline showed percentage parasite viability of 42.64% and 58.12%, respectively, against the Plasmodium falciparum strain 3D7. N-Methyl-N-phenylquinoxalin-2-amine showed MIC90 of 16.4 and MIC99 of 19 μM, while 6-chloro-2-(2-phenylethynyl)quinoxalin showed MIC90 of 8.15 and MIC99 of 9.26 μM values against Mycobacterium tuberculosis (Mtb)-H37Rv strains.

As information and communication technology develops swiftly, amount of information produced by various sources grows as well. Sorting and obtaining knowledge from this data requires significant effort which is not ensured easily by a human, meaning machine processing is taking place. Acquiring emotion from text data is an interesting area of research and it’s going through considerable expansion while being used widely. Purpose of this thesis is to create a system for positive and negative emotion detection from text along with evaluation of its performance. System was created with Java programming language and it allows training with use of large amount of data (known as Big Data), exploiting Spark library. Thesis describes structure and handling text from database used as source of input data. Classificator model was created with use of Support Vector Machines and optimized by the n-grams method.

This diploma thesis describes organic pigments of diketopyrrolopyrroles (DDPs) possessing properties applicable in attractive and perspective areas of organic electronics and photonics. The modification of the DPP skeleton was performed by nucleophilic substitution by various alkyl chains and 5 series of DPP derivatives were prepared. The regioselectivity of N-alkylation and also the photophysical properties of the prepared derivatives were studied. A key product of this work is the N,N'-ethyladamantyl derivative of DPP, which exhibited ambipolar characteristic with excellent electron mobility of 0.2 cm2 V–1 s–1. Further, the -conjugation of the above-mentioned DPP derivative was extended by 1 and 2 thiophene units at positions 3,6 and the effect of this modification on optical properties of the resulting derivatives was investigated. A new modified N,N'-unsubstituted DPP derivative was also prepared. The last point of this thesis was the study of the incorporation of formyl functional groups into the skeleton of key N,N'-ethyladamantyl DPP derivative.

Presented thesis deals with the preparation and characterization of hydrogels based on positively-charged biopolymer and negatively-charged tenside. As an appropriate representative of positively-charged polymer was chosen chitosan, because of his biocompatibility and biodegrability, and N,N,N-trimethylchitosan, which was synthetised from chitosan in this diploma thesis. The final product of synthesis was characterised by SEC-MALS, elemental analysis, infrared spectroscopy and nuclear magnetic rezonation. Interactions between these polymers and representatives of negatively-charged tensides, which are sodium dodecylsuphate and sodium tetradecylsulphate, were investigated. The main method used in this thesis was rheology, through it were investigated prepared hydrogels based on chitosan and tensides and also prepared microgels based on N,N,N-trimethylchitosan and tensides. The interactions between polymers and tensides have been proved.

Résumé confidentiel / Confidential abstract

Cette thèse porte sur l’étude des solutions périodiques du problème des N-tourbillons à vorticité positive. Ce problème, formulé par Helmholtz il y a plus de 160 ans, possède une histoire très riche et reste un domaine de recherche très actif. Pour un nombre quelconque de tourbillons et sans contrainte sur les vorticités, ce système n’est pas intégrable au sens de Liouville : on ne peut trouver de solution périodique non triviale par des méthodes explicites. Dans cette thèse, à l’aide de méthodes variationnelles, nous prouvons l’existence d’une infinité de solutions périodiques non triviales pour un système de N tourbillons à vorticités positives. De plus, lorsque les vorticités sont des nombres rationnels positifs, nous montrons qu’il n’existe qu’un nombre fini de niveaux d’énergie sur lesquels un équilibre relatif pourrait exister. Enfin, pour un système de N-tourbillons identiques, nous montrons qu’il existe une infinité de chorégraphies simples. / This thesis focuses on the study of the periodic solutions of the N-vortex problem of positive vorticity. This problem was formulated by Helmholtz more than 160 years ago and remains an active research field. For an undetermined number of vortices and general vorticities the system is not Liouville integrable and periodic solutions cannot be determined explicitly, except for relative equilibria. By using variational methods, we prove the existence of infinitely many non-trivial periodic solutions for arbitrary N and arbitrary positive vorticities. Moreover, when the vorticities are positive rational numbers, we show that there exists only finitely many energy levels on which there might exist a relative equilibrium. Finally, for the identical N-vortex problem, we show that there exists infinitely many simple choreographies.

A microscopic fungus Pseudogymnoascus destructans (Ascomycota: Pseudeurotiaceae) causes illness known as white-nose syndrome (WNS) causing death of bats during hibernation. The illness occurs in the North America and in Europe. The fungus is characteristic by asymmetrically curved conidia, by slow growth and growth at low temperatures (below 20 řC). The aim of this study is to clarify properties responsible for unique ecelogy of Pseudogymnoascus destructans by comparison with ecological related or unrelated pathogenic or nonpathogenic fungi. This part includes study of tolerance to physiological stresses and recognition of spectrum of utilizating nutrients (compounds of carbon, nitrogen, phosphorus, sulphur and nutrient supplements). Testing to physiological stresses should help to estimate a potentiality of fungus to spread out of caves. The last aim is to develop a selective isolation medium for P. destructans. Influence of several types of physiological stress (e.g. UVA, UVA with UVB, 25 řC, 30 řC, 37 řC and dryness) was investigated with fluorescent stain propidium iodide (PI) by flow cytometry. The spores of Pseudogymnoascus destructans and three fungi from underground spaces were not viable after 3 weeks at 37 řC. Other stresses did not cause a decreasing of viability or some stresses caused...