Дисертації з теми "5-D"
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1
Lalot, Jérôme. "Synthèse de 5-S-alkyl-5-thio-D-pentono-1,4-lactones, de 1-S-alkyl-1-thio-pentitols, et de 5-thio-D-pentopyranoses à partir de D-pentono-1,4-lactones." Amiens, 2003. http://www.theses.fr/2003AMIE0302.
Повний текст джерела
2
Nunes, Luciana AngÃlica da Silva. "VisÃo supersimÃtrica de modelos topolÃgicos e Branas em D=4 e D=5." Universidade Federal do CearÃ, 2008. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=2587.
Повний текст джерелаАнотація:
FundaÃÃo de Amparo à Pesquisa do Estado do CearÃCoordenaÃÃo de AperfeiÃoamento de NÃvel Superior
Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico
A linha principal dessa tese relaciona-se com teorias supersimÃtricas. Junta-se à essa linha principal uma discussÃo sobre propagadores de campos de Kalb-Ramond em branas. Na realidade os campos anti-simÃtricos sÃo outro fio condutor deste trabalho, aparecendo em quase todos os tÃpicos. Inicialmente, em branas do tipo delta de Dirac, tÃpicas dos modelos de Dvali de Randall-Sundrum, mostramos que a relaÃÃo que ocorre entre os propagadores de campos vetoriais em D=4 e D=5 dimensÃes espaÃo-temporais, continua vÃlida quando tratamos campos tensoriais anti-simÃtricos. Tal resultado subsidia especulaÃÃes de que campos tensoriais podem ser localizados na brana. No que tange a teorias com supersimetria, nossas investigaÃÃes se dividem em trÃs direÃÃes, a saber: 1) modelos topolÃgicos em D=5, no contexto da chamada pseudo-supersimetria, 2) construÃÃo de uma descriÃÃo plena do superespaÃo em D=5, inÃdita na literatura, a qual denominamos de superespaÃo intrÃnseco, para diferenciar da proposta de pseudo-supersimetria em D=5, 3) descriÃÃo do efeito Aharanov-Casher em uma teoria supersimÃtrica em D=4 com termo de quebra de Lorentz. Quanto a modelos topolÃgicos, realizamos a extensÃo pseudosupersimÃtrica em D=5, de um termo com estrutura anÃloga ao termo de Chern-Simons, mas envolvendo apenas o campo tensorial de gauge de Kalb-Ramond . Obtivemos a expansÃo completa dos supercampos e demonstramos em detalhes o nÃmero de graus de liberdade do tensor anti-simÃtrico de rank-2 em D=5. Uma vez que construÃmos a expansÃo completa do supercampo de Kalb-Ramond, determinamos o parceiro fermiÃnico do termo topolÃgico 5-dimensional. Por outro lado, insatisfeitos com o formalismo existente na literatura para tratar sistemas com supersimetria em (4+1) dimensÃes, especialmente tendo em vista aplicaÃÃes em teorias de branas, construÃmos o formalismo de superespaÃo N=1 - D=5. Encontramos os geradores, e, conseqÃentemente, as derivadas covariantes de supersimetria e mostramos que existe uma dependÃncia explÃcita da quinta coordenada. Este à um resultado que permite propagaÃÃo na dimensÃo extra, a qual nÃo à descrita no formalismo de pseudosupersimetria uma vez que sÃo usadas as mesmas derivadas covariantes de supersimetria de quatro dimensÃes. Escrevemos o Modelo de Wess-Zumino em cinco dimensÃes usando o formalismo de supersimetria intrÃnseca, assim como um supercampo vetorial, o que permitiu a construÃÃo de uma teoria manifestamente supersimÃtrica em D=5 com invariÃncia de gauge. Por fim, no contexto de uma teoria supersimÃtrica em D=4, utilizamos um ansatz para quebrar a simetria de Lorentz, simplesmente impondo que determinado campo do modelo à constante, ao mesmo tempo em que a supersimetria à preservada. Adicionamos o termo de Fayet-Illiopoulos, que nos fornece um potencial e a partir da presenÃa desse potencial escrevemos uma nova lagrangiana que permite obter o efeito Aharonov-Casher em uma teoria supersimÃtrica com termo de quebra de Lorentz. Vale a pena mencionar ainda, quatro apÃndices, a saber: convenÃÃo e revisÃo de espinores; formas diferenciais para supercampos; a prova detalhada da existÃncia de trÃs graus de liberdade on-shell em D=5 para o campo de Kalb-Ramond; e Ãlgebra de deSitter nas representaÃÃes vetorial e espinorial SO(1,4).
3
Nunes, Luciana Angélica da Silva. "Visão supersimétrica de modelos topológicos e Branas em D=4 e D=5." reponame:Repositório Institucional da UFC, 2008. http://www.repositorio.ufc.br/handle/riufc/12776.
Повний текст джерелаАнотація:
NUNES, Luciana Angélica da Silva. Visão supersimétrica de modelos topológicos e Branas em D=4 e D=5. 2008. 149 f. Tese (Doutorado em Física) - Programa de Pós-Graduação em Física, Departamento de Física, Centro de Ciências, Universidade Federal do Ceará, Fortaleza, 2008.Submitted by Edvander Pires (edvanderpires@gmail.com) on 2015-06-09T18:32:55Z No. of bitstreams: 1 2008_tese_lasnunes.pdf: 763396 bytes, checksum: 53059041868576ba43dd7ecbe7f29e5c (MD5)
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A linha principal dessa tese relaciona-se com teorias supersimétricas. Junta-se à essa linha principal uma discussão sobre propagadores de campos de Kalb-Ramond em branas. Na realidade os campos anti-simétricos são outro fio condutor deste trabalho, aparecendo em quase todos os tópicos. Inicialmente, em branas do tipo delta de Dirac, típicas dos modelos de Dvali de Randall-Sundrum, mostramos que a relação que ocorre entre os propagadores de campos vetoriais em D=4 e D=5 dimensões espaço-temporais, continua válida quando tratamos campos tensoriais anti-simétricos. Tal resultado subsidia especulações de que campos tensoriais podem ser localizados na brana. No que tange a teorias com supersimetria, nossas investigações se dividem em três direções, a saber: 1) modelos topológicos em D=5, no contexto da chamada pseudo-supersimetria, 2) construção de uma descrição plena do superespaço em D=5, inédita na literatura, a qual denominamos de superespaço intrínseco, para diferenciar da proposta de pseudo-supersimetria em D=5, 3) descrição do efeito Aharanov-Casher em uma teoria supersimétrica em D=4 com termo de quebra de Lorentz. Quanto a modelos topológicos, realizamos a extensão pseudosupersimétrica em D=5, de um termo com estrutura análoga ao termo de Chern-Simons, mas envolvendo apenas o campo tensorial de gauge de Kalb-Ramond . Obtivemos a expansão completa dos supercampos e demonstramos em detalhes o número de graus de liberdade do tensor anti-simétrico de rank-2 em D=5. Uma vez que construímos a expansão completa do supercampo de Kalb-Ramond, determinamos o parceiro fermiônico do termo topológico 5-dimensional. Por outro lado, insatisfeitos com o formalismo existente na literatura para tratar sistemas com supersimetria em (4+1) dimensões, especialmente tendo em vista aplicações em teorias de branas, construímos o formalismo de superespaço N=1 - D=5. Encontramos os geradores, e, conseqüentemente, as derivadas covariantes de supersimetria e mostramos que existe uma dependência explícita da quinta coordenada. Este é um resultado que permite propagação na dimensão extra, a qual não é descrita no formalismo de pseudosupersimetria uma vez que são usadas as mesmas derivadas covariantes de supersimetria de quatro dimensões. Escrevemos o Modelo de Wess-Zumino em cinco dimensões usando o formalismo de supersimetria intrínseca, assim como um supercampo vetorial, o que permitiu a construção de uma teoria manifestamente supersimétrica em D=5 com invariância de gauge. Por fim, no contexto de uma teoria supersimétrica em D=4, utilizamos um ansatz para quebrar a simetria de Lorentz, simplesmente impondo que determinado campo do modelo é constante, ao mesmo tempo em que a supersimetria é preservada. Adicionamos o termo de Fayet-Illiopoulos, que nos fornece um potencial e a partir da presença desse potencial escrevemos uma nova lagrangiana que permite obter o efeito Aharonov-Casher em uma teoria supersimétrica com termo de quebra de Lorentz. Vale a pena mencionar ainda, quatro apêndices, a saber: convenção e revisão de espinores; formas diferenciais para supercampos; a prova detalhada da existência de três graus de liberdade on-shell em D=5 para o campo de Kalb-Ramond; e álgebra de deSitter nas representações vetorial e espinorial SO(1,4).
4
Ostache, Nicu-Carmin. "Synthèse et fonctionnalisation de bicycles 5-5 polyazotés : pyrazolo[3,4-d]thiazoles et pyrazolo[3,4-c]pyrazoles." Thesis, Orléans, 2019. http://intranet.univ-orleans.fr/bibliotheques/theses/nicu-cosmin-ostache_3378_vm.pdf/.
Повний текст джерелаАнотація:
Les structures bicycliques azotées sont parmi les entités les plus utilisées dans le domaine thérapeutique.Les bicycles 5:5 polyazotés sont des structures moins décrites que leurs analogues 6:6 ou6:5. Malgré le potentiel pharmacologique des pyrazolo [3,4-d] thiazoles et des pyrazolo [3,4-c] pyrazoles,deux exemples de ces familles rares, seuls quelques procédés de préparation et de fonctionnalisationdirecte de ces charpentes hétérocycliques sont décrits.De ce fait, l’objectif principal de nos recherches vise à développer de nouvelles voies de synthèse vers cesdeux charpentes bicycliques et ce, à partir de substrats facilement accessibles. Des stratégies efficaces ontété mises au point et s’appuient sur réactions de condensations avec des hydrazines, des N-cyclisationsintramoléculaires, des halogénations chimiosélectives et diverses réactions de couplage-croisé. De surcroît,le motif pyrazolo[3,4-d]thiazole a été fusionné à une structure triazapentalène, afin d’évaluer les propriétésspectroscopiquesNitrogen-rich fused bicyclic structures are undisputedly one of the most used scaffolds for therapeutic use.The 5:5 polynitrogenated bicycles are moieties considerably less documented then their 6:6 or 6:5analogues. Despite the pharmacological potential of the pyrazolo[3,4-d]thiazoles and of thepyrazolo[3,4-c]pyrazoles, two examples of such rare families, only few methods of preparation and directfunctionalization of these heterocyclic moieties have been described.In this context, the main goal of our research aims at exploring new routes towards these bicyclic systemsfrom readily available and affordable starting materials. Efficient strategies were developed relying onhydrazine condensations, on intramolecular N-cyclizations, on chemo-selective halogenation and variouscross-coupling reactions. Moreover, the pyrazolo[3,4-d]thiazole entity was fused to a triazapentalenestructure in order to assess the spectroscopic properties
5
Schregenberger, Christian. "Untersuchungen an d-5-Reagenzien und Totalsynthese des Makrodiolids (+)-Conglobatin /." Zürich, 1986. http://e-collection.ethbib.ethz.ch/show?type=diss&nr=7999.
Повний текст джерела
6
Rasmussen, Betina Feldfoss. "Vitamin D intake and vitamin D status in 5 - 6 year old children in Vancouver." Thesis, University of British Columbia, 2013. http://hdl.handle.net/2429/45324.
Повний текст джерелаАнотація:
Vitamin D is important in maintaining bone health and has recently been proposed to have additional roles in the immune system and brain development. The estimated average requirement (EAR) and recommended dietary allowance (RDA) for vitamin D established by the Institute of Medicine (IOM) in 2011 is 10µg/day and 15µg/day, respectively. When this study was initiated, little information was available on whether vitamin D intakes below the recommendations in young children result in biochemical evidence of vitamin insufficiency or deficiency. Therefore the aims in this thesis were; to estimate vitamin D intakes in children, and the contribution of natural and fortified foods, and supplements; to determine the proportion of children consuming vitamin D below and above the intake recommendations; to use biochemical measures of plasma 25(OH)D to determine the proportion of vitamin D sufficient, insufficient and deficient children; and to estimate the importance of vitamin D intake and season to the children’s plasma 25(OH)D. This was a cross-sectional design with 200 children from Vancouver BC, aged 5.75 years. Vitamin D intakes were estimated using a food frequency questionnaire and 24 hr dietary recalls. Plasma 25 (OH)D was determined by HPLC-tandem mass spectrometry. The median vitamin D intake from foods was below the EAR and RDA. The children obtained 85.9% of their dietary vitamin D from supplements and fortified foods and 14.1% from natural food sources. Total median vitamin D intakes in children given or not given supplements was 13.0 (9.0) µg/day and 4.8 (3.7) µg/day, respectively, P< 0.001. Using the FFQ, 51% and 76% of the children did not meet the EAR and RDA for vitamin D, respectively. However, only 4.7% and 19.0% had a plasma 25 (OH)D below 40 nmol/L or 50 nmol/L, respectively. Unexpectedly, only 12.5% of the children who did not meet the EAR during winter months had a plasma 25 (OH)D below 40 nmol/L. The results in this thesis suggest that children depend on supplements and fortified foods to achieve the current vitamin D intake recommendations. However, despite apparent low vitamin D intakes, few children show biochemical evidence of vitamin D insufficiency, even during winter months.
7
Carretero, Paulet Lorenzo. "Caracterización a nivel molecular de los genes 1-desoxi-D-xilulosa 5-fosfato sintasa y 1-desoxi-D-xilulosa 5-fosfato reductoisomerasa de Arabidopsis thaliana." Doctoral thesis, Universitat de Barcelona, 2003. http://hdl.handle.net/10803/565500.
Повний текст джерелаАнотація:
Los isoprenoides (o terpenoides) constituyen una vasta familia de compuestos de muy diversa naturaleza estructural y funcional presentes en todos los seres vivos. Los isoprenoides sintetizados por las plantas representan la inmensa mayoría de los 29000 identificados hasta el momento, constituyéndose en la mayor familia de productos naturales conocidos. Esta gran variedad de estructuras y funciones resulta tanto más asombrosa cuando descubrimos que todos ellos, independiente de su origen, derivan del mismo intermediario común, el isopentenil pirofosfato (IPP, C5).
Estructura química y función biológica son los criterios por los que han venido clasificándose convencionalmente todos los compuestos isoprenoides. Así, entre los que podríamos clasificar como primarios se incluyen algunos metabolitos esenciales para el crecimiento y desarrollo de la planta. Por su parte, conformando los denominados metabolitos secundarios aparecen compuestos isoprenoides con funciones no esenciales, y con frecuencia específicos de determinados grupos de plantas.
La unidad más sencilla a partir de la cual se forman los restantes terpenoides es referida como isopreno, de ahí el origen etimológico del término isoprenoide para referirse colectivamente a estos compuestos, caracterizados muchos de ellos por la capacidad de descomponerse térmicamente.
Muchos de estos compuestos eran conocidos y apreciados desde muy antiguo como aromatizantes, substancias medicinales, perfumes, pigmentos o narcóticos. Consecuentemente, numerosos productos isoprenoides representan un indudable interés económico. Entre ellos destacan el caucho, aromas como el de la uva variedad moscatel, el mentol o el limoneno, nutraceúticos como las vitaminas A, D3, K y E o los fitoesteroles y compuestos farmacológicamente activos como el taxol o la digitonina. Recientemente han sido registrados los carotenos licopeno y luteína como agentes oncoprotectores.
Animales, hongos y arqueobacterias sintetizan el IPP en exclusiva a partir del acetil-CoA a través de la ruta del mevalonato (MVA). De hecho, esta ruta, descubierta en los años 50, se consideraba proveedor único para la síntesis del intermediario común a todos los isoprenoides también en organismos fotosintéticos y eubacterias. Sin embargo, la última década ha sido testigo del descubrimiento de una nueva vía de síntesis de IPP. Esta nueva vía biosintética, recientemente bautizada como del MEP, fue puesta de manifiesto originalmente en eubacterias y ha sido confirmada en diversos organismos autótrofos fotosintéticos, como las plantas superiores, las algas (excepción hecha de las euglenofitas) o las briofitas. Nuestro grupo ha sido pionero, en colaboración con el del Dr. Rohmer de la “Université Louis Pasteur” de Estrasburgo, en verificar la existencia de la ruta MEP en plantas, probablemente una de las últimas grandes ruta anabólicas por dilucidar. Adicionalmente, esta ruta ha sido confirmada también en los apicoplastos del organismo responsable de la malaria (Plasmodium falciparum) , así como en otros muchos organismos patógenos. Por todo ello, esta nueva ruta se erige en una diana ideal para el desarrollo de nuevos herbicidas y antibióticos.
A pesar de la importancia de las funciones señaladas desempeñadas por los isoprenoides, y del evidente interés que despierta su estudio, muchos aspectos de la bioquímica de estos productos y en particular de la regulación de su propia biosíntesis son relativamente poco conocidos, particularmente en lo que se refiere a aquellos sintetizados por la vía plastídica del MEP. La extrema complejidad de su metabolismo, por un lado, y la ocasionalidad de su biosíntesis tanto a nivel espacial como temporal, por otro, justifican la dificultad de su estudio.
Este trabajo pretende ser una introducción al estudio de los genes que codifican para las enzimas (DXS y DXR) que catalizan las dos primeras etapas de la ruta MEP de síntesis de IPP, utilizando para ello Arabidopsis thaliana, modelo universal de la genética molecular vegetal. De acuerdo con estos antecedentes se han planteado los siguientes objetivos que enunciamos a continuación:
1.-Identificar, aislar y caracterizar los genes DXS y DXR de A. thaliana.
2.-Resolver la función de las proteínas DXS y DXR en relación con las dos primeras etapas enzimáticas de la recientemente descubierta ruta MEP de síntesis de IPP.
3.-Analizar el patrón de expresión de los genes DXS y DXR.
4.-Determinar la localización subcelular de las proteínas DXS y DXR.
5.-Generar y examinar plantas transgénicas de sobreexpresión DXS y DXR, con el propósito de obtener información acerca de posible papel regulador en la biosíntesis de los isoprenoides plastídicos.
6.-Introducir el estudio de la interacción entre las vías MEP y del MVA de síntesis de IPP coexistentes en la célula vegetal.
8
Sanda, Komla. "Chimie fine du D-fructose : synthèse du chloromethyl-5 furannecarboxaldéhyde-2." Toulouse, INPT, 1989. http://www.theses.fr/1989INPT034G.
Повний текст джерела
9
Huang, Chang-ming. "Calculation of highly excited vibrational states of 5-D planar acetylene /." Digital version accessible at:, 1998. http://wwwlib.umi.com/cr/utexas/main.
Повний текст джерела
10
Scartozzi, Margherita. "Synthesis of oligonucleotides containing Ã-L- and ß-D-2'-deoxynucleosides and alternating 3',3'- and 5',5'-linkages." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape11/PQDD_0004/MQ44275.pdf.
Повний текст джерела
11
Scartozzi, Margherita. "Synthesis of oligonucleotides containing a-L- and b-D-2'- deoxynucleosides and alternating 3',3'- and 5'-5'-linkages." Thesis, McGill University, 1997. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=20286.
Повний текст джерелаАнотація:
Novel chimeric oligonucleotides containing L-alpha-dC monomeric units linked in the 3'3' → 5 '5' orientation have been synthesized and binding studies were performed. Thermal denaturation studies done on 7-mer sequences containing either an internal 3'3' L-alpha-dC-5'5' insert or a 3'3'-D-alpha-dC-5 '5' insert in the same position, with their complementary sequence, showed a comparable destabilization of DeltaT m = 6°C and 7°C, respectively in physiological buffer.A 19-mer sequence, complementary to a sequence near the beginning of the 5'LTR region of HIV-1 genomic mRNA, containing six alternating 3'3'-L-alpha-dC-5 '5' inserts was synthesized. Binding studies showed that this novel oligonucleotide formed stable duplexes with both its DNA and RNA targets, DeltaTm = 4°C and 8°C respectively.
Similarly, an 18-mer, also complementary to a sequence near the beginning of the 5'LTR region of HIV-1 genomic mRNA containing a terminal 3'3'-L-alpha-dC-5 '5' unit was synthesized. Binding studies demonstrated that the duplex formed showed minimal destabilization. Inhibition studies done in the presence of this modified oligonucleotide showed that the amount of (-) strong stop DNA synthesized was decreased in comparison to when the inhibition studies where done in the presence of an unmodified AON. However, due to the presence of two 5'-hydroxyl groups, this modified oligonucleotide did not serve as a substrate for the priming reaction.
The novel synthesis, as well as the characterization, of N 3-functionalized 2-beta-deoxycytidine phosphoramidite are also described.
12
Maruani, Victor. "Compréhension des mécanismes mis en jeu dans la chimie des green-binders." Thesis, Lyon, 2017. http://www.theses.fr/2017LYSE1041.
Повний текст джерелаАнотація:
La laine de verre est un matériau utilisé pour l'isolation acoustique et thermique des habitations. Ce matériau est constitué à 95% de fibres de verre et à 5% d'un liant. Bien que ce dernier soit utilisé en quantité très faible dans la formulation du matériau, il est responsable de l'obtention de bonnes propriétés mécaniques en assurant, notamment, l'intégrité structurelle du panneau de laine de verre. Pour préparer ces liants, une résine et des additifs (huile, silicone et silane) sont utilisés. Depuis une cinquantaine d'années, les résines majoritairement utilisées pour la préparation de liant pour la fabrication de la laine de verre sont de type formo-phénolique. Bien que les propriétés mécaniques des panneaux de laine de verre obtenus avec cette résine soient bonnes, il a été nécessaire d'éliminer le formaldéhyde, composé Cancérigène-Mutagène-Reprotoxique, de la formulation. C'est pourquoi de nouvelles résines ont dû être développées. Ces développements ont permis de retenir une résine pH-compatible à base de saccharose et avec des propriétés mécaniques analogues à celles obtenues avec la résine formo-phénolique. Le but de cette thèse est donc d'accéder à une connaissance approfondie des mécanismes réactionnels mis en jeu dans la formation de cette résine pour pouvoir, in fine, en optimiser ses performancesGlass wool is a material used for the acoustic and thermal insulation of dwellings. This material contains 95% of glass fibers and 5% of binder. Although this binder is used in a very small quantity in the formulation, it provides the expected mechanical properties by ensuring the structural integrity of the glass wool panel. To prepare these binders, resin and additives (oil, silicone and silane) are used. For fifty years the resins mostly used for the preparation of glass wool’s binders were the formo-phenolic’s types. Although theses resins provide good mechanical properties of the glass wool panels, it was necessary to remove the formaldehyde, a Carcinogen-Mutagen-Reprotoxic compound, from the formulation. As a consequence, new resins were developed. These developments helped us to retain a pH-compatible resin based on sucrose with mechanical properties as good as formo-phenolic’s resin. So, the aim of this thesis is to investigate the whole chemistry’s mechanism involved in the formation of this resin in order to be able to increase its performance
13
Чорноус, В. О. "Синтез 4-аміно-5-хлоро-2,6-дигідропіроло[3,4-d]піридазин-2-oнів". Thesis, БДМУ, 2021. http://dspace.bsmu.edu.ua:8080/xmlui/handle/123456789/18540.
Повний текст джерела
14
Barclay, Zoë Jade. "Signal transduction by the 5-HT2A receptor and its H452Y polymorphic variant." Thesis, University of Edinburgh, 2010. http://hdl.handle.net/1842/4483.
Повний текст джерелаАнотація:
The 5-HT2A receptor (5-HT2AR) is implicated in neuropsychiatric disorders such as schizophrenia and is thought to mediate the actions of a number of hallucinogenic and antipsychotic drugs. Additionally, certain polymorphic variants of the receptor, such as an allele resulting in substitution of amino acid 452 histidine (H) with tyrosine (Y), have been linked to schizophrenia or altered therapeutic response to antipsychotics. The 5-HT2AR utilises various intracellular signalling pathways, including the activation of phospholipase C (PLC) and phospholipase D (PLD) via recruitment of the small G-protein ADP-Ribosylation Factor (ARF). This thesis focusses on protein:protein interactions and signalling mechanisms of the 5-HT2AR and H452Y-5-HT2AR receptor variant. Both ARF1 and PLD1 have previously been shown to bind to the carboxy-terminal tail (ct) of the 5-HT2AR. In chapter three it is demonstrated that the 5-HT2AR can activate PLD in an ARF-dependent manner, primarily through the PLD1 isoform. GST-fusion proteins of truncated and mutated variants of the receptor ct are used to show that ARF1 and PLD1 independently bind to distinct sites. Coimmunoprecipitation, GST-fusion protein studies and PLD activity assays demonstrate that the introduction of the H452Y mutation decreases the physical interactions between the receptor and PLD1, as well as decreasing 5-HT2ARmediated PLD activation. In chapter four, potential mechanisms of wild-type and H452Y-5-HT2AR desensitisation are explored. It is shown that β-arrestin 2 (β-arr 2) confers a decrease in H452Y-5-HT2AR-mediated PLC activity, despite having no significant effect upon wild-type 5-HT2AR responses. The H452Y-5-HT2AR variant is also shown, by GST-fusion protein studies, to bind β-arr 2 more strongly. The H452Y-5-HT2AR additionally mediates increased levels of 5-HT-induced ERK phosphorylation compared to the wild type 5-HT2AR, potentially through increased scaffolding of ERK activation complexes by receptor-bound β-arr 2. Chapter five focusses on possible interactions of the 5-HT2AR with the Ca2+-binding proteins annexin A2, S100B and the annexin A2 partner p11, together with the functional consequences of these interactions. Co-immunoprecipiation and GST-fusion protein studies show that annexin A2 binds specifically to the 5-HT2AR ct. Furthermore, annexin A2 (but not S100B or p11) is shown to result in an amplification of 5-HT2AR-mediated PLC responses. These findings provide a greater insight into some of the signal transduction mechanisms of the 5-HT2AR and their perturbation in the H452Y polymorphic form of the receptor, and understanding of the molecular mechanisms underlying neuropsychiatric diseases in patient subgroups, potentially leading to improved therapeutic treatments.
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Bertolini, Wagner Luiz Heleno Marcus. "A influência do D-limoneno como promotor de absorção de ácido 5-aminolevulínico para Terapia Fotodinâmica do câncer de pele: avaliação in vitro e in vivo da permeação e retenção cutâneas." Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/60/60137/tde-12052009-191324/.
Повний текст джерелаАнотація:
BERTOLINI, WAGNER L. H. M. A influência do D-limoneno como promotor de absorção do ácido 5-aminolevulínico para Terapia Fotodinâmica do câncer de pele: avaliação in vitro e in vivo da permeação e retenção cutâneas. 2009 118f. Tese (Doutorado). Faculdade de Ciências Farmacêuticas de Ribeirão Preto Preto Universidade de São Paulo, Ribeirão Preto, 2009. O câncer é a segunda doença principal do planeta, muito próximo de se tornar a mais incidente. Os tratamentos tradicionais do câncer, tais como cirurgia, radioterapia e quimioterapia apresentam severos efeitos colaterais ao paciente devido à citotoxicidade que podem causar às células normais, além das cancerosas. Objetivando minimizar estes efeitos indesejáveis pesquisadores de diversas áreas afins vislumbram novas técnicas, novos tipos e formas de tratamentos que apresentem um melhor perfil terapêutico; que possam agir de forma mais seletiva contra as células cancerosas, minorando os efeitos indesejáveis em relação às células saudáveis. Dentre as técnicas pesquisadas destaca-se a Terapia Fotodinâmica (TFD). Esta é uma técnica de tratamento nova e promissora. A técnica do tratamento consiste em aplicar, no tecido alvo, substâncias fotossensibilizantes, posteriormente ativadas com luz de comprimentos de onda específicos, com a finalidade de produzir destruição celular, por meio da ação de produtos citotóxicos fotoativados. Destaca-se a seletividade apresentada pela técnica, que deve ser reconhecida como uma das vantagens entre as técnicas empregadas no tratamento do câncer. O presente trabalho objetiva verificar a influência do D-limoneno como promotor de permeação do ácido 5-aminolevulínico (5-ALA) em aplicação tópica. Isto visa aumentar a permeação do 5-ALA quando aplicado topicamente. O 5-ALA é convertido a protoporfirina-IX (PpIX) pela via do ciclo Heme. Esta é um potente agente fotossensibilizador endógeno. O interesse no uso deste promotor foi aumentar a taxa de penetração do 5-ALA, possibilitando a permeação de maiores quantidades do fármaco em questão. Para isto foram realizados estudos de permeação in vitro do 5-ALA, em concentração de 1% (p/p) utilizando-se formulações (emulsões O/A) com diferentes concentrações do promotor D-limoneno (0, 5, 10, 20 e 30%), (p/p). Observou-se que o fluxo in vitro do 5-ALA através da pele de orelha de porco aumentou para todas as formulações empregadas quando comparado ao controle, sem D-limoneno, para um período de estudo de 12h. A retenção no estrato córneo e na [epiderme + derme] apresentou aumento significativo, evidenciando, assim, um efeito eficiente do D-limoneno como promotor. Experimentos in vivo foram conduzidos em camundongos objetivando a análise do efeito da formulação na produção e acúmulo de PpIX na pele. Observou-se que o D-limoneno aumentou significantemente a quantidade de PpIX extraída da pele. Os resultados in vitro e in vivo mostraram o potencial do D-limoneno como promotor de absorção cutânea para o 5-ALA para a TFD tópica do cancer de pele.BERTOLINI, WAGNER L. H. M. D-limonene influence in the cutaneous penetration enhancer for 5-aminolevulinic acid in photodynamic therapy of skin cancer: in vitro and in vivo skin permeation and retention studies. 2009 118f. Thesis (Doctoral). Faculdade de Ciências Farmacêuticas de Ribeirão Preto Preto Universidade de São Paulo, Ribeirão Preto, 2009. The topical administration of 5-ALA has been distinguished on skin cancer photodynamic therapy (PDT) because of its efficiency in the treatment of tumors and the reduced phototoxic collateral effects. However, this effectiveness is limited by its low penetration in the skin. A proposal to optimize the 5-ALA penetration in the skin is the use of cutaneous penetration enhancers, which seek to alter the cutaneous barrier for many bioactive molecules. The aim of this work was the pharmaceutical development of formulations containing D-limonene as a cutaneous penetration enhancer, seeking the increase of the cutaneous penetration of 5-ALA for skin cancer PDT. The in vitro flux of 5-ALA present in 1% (w/w) from different formulations containing D-limonene (20 e 30% w/w) was significantly increased after 12 hours of experiment, in comparison with formulations without D-limonene, mainly for the formulations containing 20% and 30% of D-limonene with 1% of 5-ALA (1,45 and 2,01 times, respectively). The stratum corneum (SC) and [epidermis + dermis] without SC retention were also significantly increased, showing an enhancer effect of the promoter. In addition, in vivo experiments were accomplished in mice, with the purpose of analyzing the formulation effect on the PpIX production and accumulation in the skin. It was observed that the penetration enhancer\'s presence significantly increased the amount of PpIX extracted from the skin. Both in vitro and in vivo results showed the potentiality of the formulations containing D-limonene as a cutaneous penetration enhancer for 5-ALA delivery on the skin cancer PDT.
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Englert, Nadine Esther [Verfasser]. "NMR Strukturanalyse der 1-Deoxy-D-xylulose-5-phosphat Reduktoisomerase / Nadine Esther Englert." Gießen : Universitätsbibliothek, 2012. http://d-nb.info/1064837557/34.
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Brewer, Angela. "The regulation of PHEX expression by 5/6 nephrectomy and 1,25-dihydroxyvitamin D₃ /." Thesis, McGill University, 2002. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=78328.
Повний текст джерелаАнотація:
Mutations in the PHEX gene are responsible for X-linked hypophosphatemia, the most prevalent form of inherited rickets in humans. PHEX is an endopeptidase that is expressed in bone and parathyroid gland and shown to cleave parathyroid hormone [PTH]. To determine whether PHEX is regulated by PTH we used two models: (1) 5/6 nephrectomized [5/6 Nx] rats which exhibit significant hyperparathyroidism and (2) 1,25-dihydroxyvitamin D3 [1,25(OH)2D]-treated rats, which are characterized by marked hypoparathyroidism. We demonstrate that 5/6 Nx elicits an increase in PHEX mRNA and protein abundance in rat tibia whereas 1,25(OH)2D causes a decrease in both tibial parameters. In addition, administration of 1,25(OH)2D to 5/6 Nx rats blunts the increase in PHEX gene expression in bone. We also observe a significant correlation between serum PTH concentration and tibial PHEX expression. Our data thus provides evidence for a role of PTH in the regulation of PHEX expression.
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Le, Bouc Géraldine. "Pipéridines et pyrrolizidinones polyhydroxylées : synthèses de la 1, 5, 6-tridésoxy-1, 5-imino-D-allo-heptitol et de la 1, 5, 6-tridésoxy-1, 5-imino-L-talo-heptitol et approche synthétique de la (+)-amphorogynine B." Versailles-St Quentin en Yvelines, 2008. http://www.theses.fr/2008VERS0042.
Повний текст джерелаАнотація:
Les alcaloïdes polyhydroxylés sont largement répandus dans la nature en particulier dans les plantes ou les microorganismes. Leur intérêt grandissant est dû à leurs propriétés biologiques qui font d’eux d’éventuels agents thérapeutiques. En effet, ces alcaloïdes peuvent être des inhibiteurs puissants et sélectifs de glycosidases. C’est pourquoi notre travail s’est focalisé, en particulier, sur les pipéridines et pyrrolizidinones polyhydroxylées. L’étape clé des synthèses est une hydrogénation catalytique diastéréosélective de b-cétoesters fonctionnalisés. Dans un premier temps, nous avons synthétisé deux nouvelles pipéridines polyhydroxylées, épimères l’une de l’autre en C-5: la 1,5,6-tridésoxy-1,5- imino-D-allo-heptitol et de la 1 , 5 , 6- tridésoxy-1,5-imino-L-talo-heptitol. Puis nous nous sommes intéressés à l’approche des structures des amphorogynines. Nous avons développé deux voies différentes pour accéder à quatre pyrrolizidinones, précurseurs de pyrrolizidines dihydroxyléesPolyhydroxylated alkaloïds are widespread in plants and microorganisms. These alkaloids are arousing great interest as potential therapeutic agents. In fact, it can be potent and highly selective glycosidases inhibitors. For this reason, this work has focused in particular on polyhydroxylated piperidines and pyrrolizidinones. The key step of these syntheses is a diastereoselective and catalytic hydrogenation of functionalized b-kétoesters. In a first part, we synthesized two new polyhydroxylated piperidines, epimers one of the other at C-5: 1,5,6-trideoxy-1,5-imino-D-allo-heptitol and 1,5,6-trideoxy- 1,5-imino-L-talo-heptitol. Then, we are interested in approach of amphorogynines’s structures. We developed two different tracks for obtain four pyrrolizidinones, precursors of ihydroxylated pyrrolizidines
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Moore, Casey Benjamin. "Cell cycle affects accumulation of β-D-5-o-Carboranyl-2'-Deoxyuridine(D-CDU) in human glioma cell line". Thesis, Georgia Institute of Technology, 2002. http://hdl.handle.net/1853/16348.
Повний текст джерела
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Chpoun, Amer. "Contribution a l'etude d'ecoulements hypersoniques (m=5) sur une rampe de compression en configuration 2-d et 3-d." Paris 6, 1988. http://www.theses.fr/1988PA06A005.
Повний текст джерелаАнотація:
Etude experimentale de l'influence de l'ecoulement transversal sur les distributions du flux thermique et de la pression parietale. Determination des grandeurs caracteristiques de la zone de decollement. Etude de l'apparition de la transition dans la zone du decollement en fonction du nombre de reynolds. Solution numerique pour la distribution de pression dans le cas de l'interaction laminaire
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Chpoun, Amer. "Contribution à l'étude d'écoulements hypersoniques (M=5) sur une rampe de compression en configuration 2-D et 3-D." Paris 6, 1988. http://www.theses.fr/1988PA066149.
Повний текст джерелаАнотація:
Etude expérimentale de l'influence de l'écoulement transversal sur les distributions du flux thermique et de la pression pariétale. Détermination des grandeurs caractéristiques de la zone de décollement. Etude de l'apparition de la transition dans la zone du décollement en fonction du nombre de Reynolds. Solution numérique pour la distribution de pression dans le cas de l'interaction laminaire
22
Chpoun, Amer. "Contribution à l'étude d'écoulements hypersoniques, Mach 5, sur une rampe de compression en configuration 2-D et 3-D." Grenoble 2 : ANRT, 1988. http://catalogue.bnf.fr/ark:/12148/cb37612629f.
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23
Hebinger, Grégory. "Biosynthèse des isoprénoïdes : la 1-désoxy-D-xylulose 5-phosphate synthase, une enzyme non spécifique du D-glycéraldéhyde 3-phosphate." Strasbourg, 2010. http://www.theses.fr/2010STRA6294.
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White, Justin K. "Investigations into the Non-Mevalonate Isoprenoid Biosynthesis Pathway's First Two Enzymes utilizing Hybrid QM/MM Techniques." Scholar Commons, 2017. http://scholarcommons.usf.edu/etd/7107.
Повний текст джерелаАнотація:
Molecular drug design begins with the identication of a problem to solve. This work identies the growing resistance among human pathogens to current treatments. Once the problem is identied and understood, solutions must be proposed. This one is straight forward, we need new antimicrobial drugs. More specically, we need to identify novel targets to inhibit. A large portion of antibiotics focus on disruption of macromolecular production while only a few target metabolic systems. Finally, you need to propose solutions based on the information gathered. In order to avoid existing resistance, it is important to avoid the macromolecular route and focus on metabolic enzymes. Preferably, the pathway would have little overlap or similarity with pathways found in the treatment organism. With this in mind, the non-mevalonate (NMA) pathway poses as a very good target for drug design. Many pathogens have been found to be strictly dependent on this pathway while it is absent in humans. Additionally, fosmidomycin has already been shown to inhibit this pathway. Initially thought to just inhibit the 1-deoxy-D-xylulose 5- phosphate (DXP) reductoisomerase (DXR), it has been shown to inhibit several enzymes along the path to a lesser extent. Ideally, this could be repeated or improve upon for future drug design.
With this in mind, the initial stages of the rst two enzymes of the NMA pathway were examined utilizing quantum mechanical/molecular mechanical (QM/MM) techniques. The rst enzyme was DXP synthase (DXS), which catalyzes a transketolase-like condensation of pyruvate and glyceraldehyde-3-phosphate to produce DXP. DXS and other transketolases are dependent on the thiamine diphosphate (TDP) cofactor, which must be deprotonated of the imidazolium C2 atom producing a highly reactive ylide. A tautomerization occurs prior to this deprotonation to prime the pyrimidinium ring N4 atom to perform the C2 abstraction. The question at hand was the identity of a general base to perform the N4 abstraction. The results favored a water-mediate mechanism with a higher than usual Ez of 22.7 kcal/mol. An observation pertaining the tautomerization pertained to the aromaticity of the pyrimidine ring. Upon further investigation, aromaticity was found to play a signicant role in the ΔE observed. Aromaticity might contribute 14.2 kcal/mol to the barrier height. This high energy would drive the reaction forward producing the ylide.
Investigation of the DXR enzyme followed this work. Initially, the work was going to focus on the 2 mechanisms proposed for activity, alpha-ketol rearrangement and retroaldol/ aldol mechanism. Subsequent publications involving secondary kinetic isotope effects (KIEs) add to the pile of evidence supporting the retro-aldol/aldol mechanism. So the project was retooled to investigate the energetic dierences between two metal binding modes. The results of this work support a metal coordination across the C3-C4 bond, which eventually extends coordination to include the C2 oxygen. This conformation was help explain the tight binding eecting observation of the putative intermediates (transition states) and aldehyde intermediate. Additionally, as the C2-C3 mode consistently transfers a proton to the phosphate group of DXP or produces an elongated C-O bond, the C2-C3 mode would not be favorable.
Further investigations of these enzymes (e.g. completing the step begin, continuing through the reaction) could provide further illumination into the mechanism of action and possibly reveal new avenues of drug design. Examining the enzymes downstream in the NMA pathway might provide details of interest. Of particular interest is the radical reaction proposed for HDR/IspH. The nal step of the pathway produces IDP and DMADP in a 4:1 proportion, which corresponds to the general system requirements for production of the long chain, branched isoprenoids. It would be interesting to compute the mechanism to see if energetics could provide further insights. Additionally, normal mode analysis coupled with vibrational subsystem analysis could identify allosteric sites for feedback sensitivity.
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Mbazoa, Djama Céline. "Valorisation chimique du D-fructose : synthèse et stabilité du 5-hydroxyméthyl furane 2-carboxaldéhyde." Toulouse, INPT, 1990. http://www.theses.fr/1990INPT030G.
Повний текст джерелаАнотація:
La synthese du 5-hydroxymethyl 2-carboxaldehyde furane ou hydroxymethylfurfural est obtenu par deshydratation intramoleculaire des hexoses et en particulier le d-fructose. La creation est menee dans le dimethylsulfoxyde, sous l'action de la chaleur, en l'absence de catalyseur ajoute. L'etude cinetique, l'origine du deficit bilan matiere ainsi que le role specifique du dimethylsulfoxyde ont fait l'objet d'une etude detaillee. L'etude de l'influence des differents facteurs a travers la realisation de plans d'experience a permis d'optimiser les conditions d'obtention de l'hydroxymethylfurfural. Apres l'addition d'eau en fin de reaction, le milieu de synthese est filtre pour eliminer les residus organiques ou humaines. L'addition d'un tiers solvant, non miscible a l'eau, permet d'extraire l'hydroxymethylfurfural. Cet extrait est ensuite soumis a un processus de decolaration et de cristallisation. Les cristaux d'hydroxymethylfurfural obtenus, en presence de trace d'antioxydant presentent une stabilite remarquable
26
Bing, Zhou. "Crosshole resistivity and acoustic velocity imaging : S.5-D helmholtz equation modeling and inversion /." Title page, contents and abstract only, 1998. http://web4.library.adelaide.edu.au/theses/09PH/09phb613.pdf.
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Montel, Sonia. "La 1-Deoxy-D-Xylulose-5-Phosphate Reductoisomerase, une métalloenzyme cible pour l'élaboration d'inhibiteurs chélatants." Thesis, Montpellier, Ecole nationale supérieure de chimie, 2012. http://www.theses.fr/2012ENCM0013.
Повний текст джерелаАнотація:
La voie non-mévalonate est fortement présente chez les plantes et les bactéries mais est absente chez les mammifères. C'est pourquoi inhiber la synthèse des isoprénoïdes et identifier un inhibiteur de cette voie enzymatique contribuera grandement à la recherche de nouveaux antibiotiques, antifongiques et herbicides. Les propriétés uniques de la 1-deoxy-D-xylulose 5-phosphate reductoisomérase (DXR), l'enzyme centrale de cette voie enzymatique, en font une cible très intéressante pour la synthèse de nouveaux composés. La Fosmidomycine agit comme un inhibiteur de la DXR et reste aujourd'hui, avec son homologue acétylé FR90098, la référence en termes d'inhibiteur même si de nombreux efforts ont été faits pour la synthèse d'analogues depuis plusieurs années comme expliqué dans le premier chapitre avec la mise en relation de la structure des composés et leur activité. L'analyse de la diffraction des rayons X de la DXR avec la Fosmidomycine où le substrat naturel montre que la fonction phosphonate ou phosphate interagit avec une poche polaire hautement spécifique dans le site actif de l'enzyme permettant peu de modifications. Par comparaison, la fonction acide hydroxamique qui chélate le cation de l'enzyme offre la possibilité de modifications par l'introduction d'autres fonctions complexantes. Dans ce contexte, de nombreuses modifications comme l'introduction de fonctions carbamoylphosphinate, amidoxime, N-hydroxyurée et dérivées d'uraciles comme unités complexantes ont été synthétisées pour trouver des nouvelles familles d'inhibiteurs de la DXR. Toutes ces fonctions possèdent des propriétés de chélation intéressantes. En effet, elles ont déjà conduit à de puissants inhibiteurs de différentes métalloenzymesThe non-mevalonate pathway is highly present in higher plants, protozoa and bacteria but as no equivalent in mammals. That is why shut down isoprenoid biosynthesis and identify a non-mevalonate pathway inhibitor would greatly contribute to the search for safer antibiotics, antimalarials and for our concern herbicides. The unique properties of the 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR), the central enzyme of this pathway, make it a remarkable and attractive target for drug design. Fosmidomycin acts as an inhibitor of DXR and still remains, along with its N-acetyl homologue FR90098, one of the most potent inhibitor ever known even if extensive work on the development of Fosmidomycin analogue derivatives have been developed since the last decade as demonstrated in the first chapter with the development of a structure activity relationship of all the potential inhibitors of this enzyme already reported in the literature. The X-ray diffraction analysis of the co-crystals of DXR and Fosmidomycin or substrate shows that the phosphonic/phosphate group interacts with a highly specific polar pocket in the enzyme site, allowing only few structural modifications. By contrast, the cation chelating subunit represented by the hydroxamic acid function offers fine tuning possibilities for the complexation abilities as well as potential secondary interactions with the NADPH cofactor or directly with the enzyme. In this context, several modifications such as the introduction of carbamoylphosphinate, amidoxime, N-hydroxyurea and uracil complexing subunits have been made in order to find new families of DXR inhibitors. All of these functions show promising chelation capabilities as they already led to potent inhibitors of different metalloenzymes
28
Severn, John Richard. "Studies of d'5-d'9 first row transition metal and tin complexes containing 1-aza-allyl; or #beta#-diketiminato ligands." Thesis, University of Sussex, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.285127.
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29
PURPURA, LUCA. "La risoluzione dei contrasti nella gestione di società (art. 37 d. lgs. N. 5/2003)." Doctoral thesis, Università Cattolica del Sacro Cuore, 2007. http://hdl.handle.net/10280/91.
Повний текст джерелаАнотація:
La tesi prende in esame lo strumento giuridico, denominato arbitrato economico , introdotto dal d. lgs. 17 febbraio 2003, n. 5. Questa disposizione consente di fissare, nell'atto costitutivo delle società di persone e di capitali, clausole che stabiliscono il deferimento a soggetti terzi dei contrasti tra coloro che hanno il potere di amministrazione in ordine alle decisioni da prendere nella gestione sociale. Questo sistema di risoluzione dei contrasti in materia di gestione rappresenta, nella realtà italiana, una sostanziale novità: esso pone numerosi interrogativi in punto tanto di fattispecie, quanto di disciplina. La tesi tenta di affrontare le principali questioni sollevate dall' arbitrato economico anche alla luce dell'esperienza comparatistica (in particolare: tedesca e statunitense).
30
Chudziak, Christopher Mark. "Production, characterisation and modification of 1-deoxy-d-xylulose-5-phosphate synthase as a biocatalyst." Thesis, University College London (University of London), 2007. http://discovery.ucl.ac.uk/1445214/.
Повний текст джерелаАнотація:
The use of biotransformations in organic synthesis is a small but growing field. Biotransformations can be used for many steps which prove difficult with traditional chemistry, particularly stereospecific syntheses and chiral resolutions. However, to enable the increasing use of biotransformations in chemical synthesis, a broader range of biocatalysts will be required than those of which we are currently aware. Bioprospecting and genome sequencing are increasing the awareness of Nature's library of biocatalysts. These enzymes need to be characterised for their use as biocatalysts, and where necessary modified to meet needs that may not be catered for in nature. One currently used biocatalyst is transketolase. Transketolase is an enzyme which is produced by most organisms. As a biocatalyst it is most often extracted from spinach, or produced by recombinant Escherichia coli. Transketolase carries out a stereospecific carbon-carbon bond formation, removing a 2-carbon ketol group from a ketose sugar, and adding it to the aldehyde group of the aldose sugar. It is a useful biocatalyst as it has a broad substrate specificity. Significantly it will use hydroxypyruvate as the ketol donor, thus liberating carbon dioxide and driving the reaction in a forward direction. In this thesis the transketolase-like enzyme, 1-Deoxy-D-xylulose 5-Phosphate Synthase (DOX-P Synthase), is identified as another possible biocatalyst. Significantly DOX-P Synthase catalyses the addition of a carbonyl unit, not from hydroxypyruvate, but from pyruvate, a reaction which cannot be catalysed by transketolase. This thesis therefore describes studies that aimed to produce recombinant DOX-P Synthase as a biocatalyst, and to optimise its production. Further studies aimed to characterise the properties of DOX-P Synthase, with the aim of optimising its use as a biocatalyst. Analysis of the substrate range of DOX-P Synthase could then be used to describe the set of reactions for which it would be a useful biocatalyst. Finally, this thesis describes modifications made to the enzyme, carried out by site-directed mutagenesis, and the effects on enzyme properties.
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Larousse, Christian. "Valorisation chimique du D-fructose : synthèse de l'oxyde de bis (5-méthylène furane-2-carboxaldéhyde)." Toulouse, INPT, 1992. http://www.theses.fr/1992INPT041G.
Повний текст джерелаАнотація:
La synthese de l'oxyde de bis(5-methylene furane-2-carboxaldehyde) est etudiee. Un bilan bibliographique comparatif sur les differentes methodes de deshydratation intermoleculaire du 5-hydroxymethylfurane-2-carboxaldehyde est etabli. Plusieurs methodes sont comparees. L'etherification est menee par voie thermique (155c) en l'absence de tiers solvant et en presence d'une faible quantite de dimethylsulfoxyde (rapport molaire hydroxymethylfurfural/dimethylsulfoxyde=11). L'optimisation des conditions d'obtention grace a la realisation d'un plan d'experiences a permis d'atteindre une selectivite de 84% pour un rendement de 59% en 1 heure. Une technique originale de synthese par mise en uvre des micro-ondes est proposee; les temps de reaction sont reduits de 30 fois. L'etude de la formation des produits secondaires a permis d'ameliorer la selectivite (94%) apres elimination des impuretes de l'hydroxymethylfurfural par recristallisation. La purification de l'oxyde de bis(5-methylene furane-2-carboxaldehyde) est obtenu par cristallisation dans l'eau avec des rendements de 96%. Un procede d'obtention de l'oxyde de bis(5-methylene furane-2-carboxaldehyde) pur a partir de d-fructose est propose. Il permet de recycler le hmf non converti et le dimethylsulfoxyde, et d'atteindre des rendements de 63% par rapport au d-fructose
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BONNETTE, CORINNE. "Synthese et proprietes inhibitrices d'un nouvel inhibiteur des phosphoglucose isomerases : l'acide 5-phosphate-d-arabinohydroxamique." Paris 11, 1996. http://www.theses.fr/1996PA112475.
Повний текст джерелаАнотація:
Les phosphoglucose isomerases (pgi) sont des enzymes de la glycolyse qui catalysent l'interconversion reversible du 6-phosphate-d-glucose en 6-phosphate-d-fructose. Chez plusieurs parasites, tels que le plasmodium falciparum et le trypanosoma brucei, seule la glycolyse anaerobie du glucose exogene fournit l'energie necessaire a leur developpement. Dans un but pharmacologique antiparasitaire, nous avons developpe la synthese d'un inhibiteur potentiel analogue de l'etat de transition des pgi: l'acide 5-phosphate-d-arabinohydroxamique. La synthese de ce derive tout a fait nouveau a ete realisee a partir du d-arabinose et requiert une succession de reactions de protection et de deprotection permettant l'introduction selective, d'une part, de la fonction hydroxamate sur le c1, et d'autre part, du groupement phosphate en c5. Cette voie de synthese nous a egalement permis d'obtenir le meilleur inhibiteur connu de la pgi, l'acide 5-phosphate-d-arabinonate. L'etude des proprietes inhibitrices du 5-phosphate-d-arabinohydroxamate nous a permis de mettre en evidence les points suivants: (i) a ce jour, ce compose est le meilleur inhibiteur des phosphoglucose isomerases de muscle de lapin, de levure, de bacillus stearothermophilus et de trypanosoma brucei. Pour la pgi de muscle de lapin, les valeurs de km et ki obtenues a ph 8,0 sont respectivement de 0,0800 nm et 0,0014 mm, (ii) ce pouvoir d'inhibition est fortement dependant du ph, (iii) aucune specificite significative vis-a-vis d'une des pgi etudiees n'a ete observee
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Araujo, Itauá Leston. "Resposta imune humoral em bovinos induzida pela glicoproteína D recombinante de herpesvírus bovino tipo 5." Universidade Federal de Pelotas, 2014. http://guaiaca.ufpel.edu.br/handle/123456789/1235.
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Previous issue date: 2014-02-27Glycoprotein D (gD) is essential for attachment and penetration of bovine herpesvirus type 5 (BoHV-5) into susceptible cells, and is a major target of host immune systems, inducing strong humoral and cellular immune responses. The immunogenicity of recombinant BoHV-5 (rgD5) expressed in Pichia pastoris was evaluated in bovines. Vaccines formulated with 100 μg rgD5 dose and adjuvants (Montanide ISA50V2 or Aluminum Hydroxide) with or without inactivated BoHV-5 or rgD5 without adjuvants were administered intramuscularly. A commercial vaccine was also used as control. The vaccine formulation rgD5 + ISA50V2 stimulated humoral immune responses after two doses, and higher titer of neutralizing antibodies were obtained in all three oil-based adjuvants formulations when compared to Hydroxide Aluminium adjuvant or the commercial vaccine. The vaccine BoHV-5 + rgD5 + ISA50V2 stimulated titers of neutralizing antibodies approximately 8 log2, which demonstrated higher correlations on the Indirect ELISA. Together, the results suggest that the recombinant gD5 conserved neutralizing epitopes and was able to stimulate a efficient humoral immune response in bovines.
A glicoproteína D (gD) é essencial para ligação e penetração de herpesvírus bovino 5 (BoHV-5) em células suscetíveis, e é um alvo importante do sistema imune do hospedeiro, induzindo respostas imunes humoral e celular. A imunogenicidade da glicoproteína D recombinante de BoHV-5 (rgD5) expressa em Pichia pastoris foi avaliada em bovinos. Vacinas formuladas com 100 μg de rgD5 por dose e adjuvante a base de óleo (Montanide ISA50V2) ou hidróxido de alumínio, com ou sem adição de BoHV-5 inativado foram administradas via intramuscular, e uma vacina comercial utilizada como controle. A vacina rgD5 + ISA50V2 estimulou resposta imune humoral após duas doses, e os mais elevados títulos de anticorpos neutralizantes foram obtidos em todas as três formulações de adjuvantes à base de óleo quando comparado com a formulação de vacinas de adjuvante de hidróxido de alumínio e vacina comercial. A vacina BoHV-5 + rgD5 + ISA50V2 estimulou títulos de anticorpos neutralizantes aproximadamente a 8 log2, demonstrando correlação significativa com o ELISA indireto. Em conjunto, os resultados sugerem que a rgD5 conservou epítopos neutralizantes e foi capaz de estimular uma resposta imune humoral eficiente em bovinos.
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Pham, Thu. "Vitamin D status of immigrant and ethnic minority children ages 2 to 5 y in Montreal." Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=107657.
Повний текст джерелаАнотація:
Vitamin D (VTD) status is lower in ethnic minorities compared to White Canadians, but this has not been studied in children under 6 y of age. Therefore, the objective of this study was to estimate the prevalence of VTD insufficiency and to identify explanatory variables for 502 children (2 to 5 y) attending Montréal daycares in a cross-sectional study between June 2010 and 2011. Capillary blood sampling demonstrated that 25-hydroxy vitamin D (25(OH)D) concentration was ≤ 50 nmol/L in 10% of White children (n = 262), 14% of Black (n = 36), 0% of Hispanic (n = 15), 16% of Arab (n = 45), 9% of Asian (n = 43) and 14% of Mixed ethnicities (n = 101). The main predictor was sun index for White (∆r2 = 0.09, P = 0.263), VTD intake from supplement for Arab (∆r2 = 0.18, P < 0.001) and Mixed (∆r2 = 0.16, P < 0.001) income for Black (∆r2 = 0.28, P = 0.009) and skin type for Asian (∆r2 = 0.18, P < 0.001). More than 80% of children attending daycares in Montréal have adequate vitamin D status, regardless of ethnicity, immigration status, years of residence or SES. Since the explanatory variables for VTD status differed among ethnicities, strategies to improve VTD status in those with low status will need to consider the unique needs of each ethnic group.Les niveaux sériques de vitamine D des minorités visibles sont inférieures à celui des Blancs, mais n'a pas été étudié auprès des enfants moins de 6 ans. Donc, l'objective de cette étude était d'estimer la prévalence d'insuffisance en vitamine D et d'identifier les paramètres explicatifs pour 502 enfants (2 à 5 ans) fréquentant les garderies de Montréal entre Juin 2010 et 2011. La concentration sérique capillaire de 25-hydroxy vitamine D (25(OH)D) était ≤ 50 nmol/L dans 10% des enfants Blancs (n = 262), 14% des Noirs (n = 36), 0% des Latino-Américains (n = 15) , 16% des Arabes (n = 45), 9% des Asiatiques (n = 43) and 14% des Mélangés (n = 101). Le paramètre explicatif principale était l'exposition au soleil pour les enfants Blancs (r2 = 0.0.09, P = 0.263), l'apport de supplément en vitamine D pour les Arabes (r2 = 0.18, P < 0.001) et Mélangés (r2 = 0.16, P < 0.001), le revenu familiale pour les Noirs (r2 = 0.28, P = 0.009) et le type de peau pour les Asiatiques (r2 = 0.18, P < 0.001). Plus de 80% des enfants des garderies avaient des taux adéquats de vitamine D peu importe l'ethnicité, le statut d'immigration, le nombre d'année de résidence au Canada ou le statut socioéconomique. Puisque les paramètres explicatifs du statut de vitamine D étaient différents pour chaque ethnicité, les stratégies pour améliorer le statut de vitamine D pour ceux qui présentent de faibles taux devront considérer les besoins unique de chaque groupe ethnique.
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SANTOS, Arthur Bernardo de Souza. "Cromóforos rígidos derivados de tiazol o [5, 4-d] tiazol: cristais líquidos e sais orgânicos fotocromáticos." Universidade Federal de Pernambuco, 2016. https://repositorio.ufpe.br/handle/123456789/17508.
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ATUALIZADA DISSERTAÇÃO_ARTHUR_UFPE_.pdf: 6640779 bytes, checksum: 54162674f1fcaee2b4fef8836f21cd72 (MD5)Made available in DSpace on 2016-07-21T16:17:26Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) ATUALIZADA DISSERTAÇÃO_ARTHUR_UFPE_.pdf: 6640779 bytes, checksum: 54162674f1fcaee2b4fef8836f21cd72 (MD5) Previous issue date: 2016-03-30
CNPQ
O estudo das propriedades de materiais orgânicos tem chamado atenção devido sua versatilidade estrutural e de composição que podem moldar suas propriedades físicas e químicas. Neste trabalho preparamos seis cromóforos rígidos contendo o heterociclo tiazolo[5,4-d]tiazol (Thz) como espaçador aromático, e grupos terminais piridínicos ou carboxílicos. Desta forma trabalhamos com duas linhas de pesquisa: foto-eletroquímica para os derivados piridínicos e síntese e caracterização de cristais líquidos (CLs). Investigamos as propriedades fotoquímicas e processos redox das bipiridinas X,X'-(tiazolo[5,4-d]tiazol-2,5- dil)bis(piridil) (X,X’ = 2,2’; 3,3’ ou 4,4’). Em solução, apresentaram propriedades acidocrômica via foto- e eletrodissociação de solventes clorados. A seguir, preparamos sais de trifluoracetato dos bipiridínio (viologens), que apresentaram propriedades fotocromáticas via transferência de elétron quando expostos à radiação UVB. Utilizamos os derivados carboxílicos como centros rígidos para a preparação de cristais líquidos. Escolhemos o grupo carboxilato como precursor sintético dos conectores orgânicos: éster, amida e 1,3,4-oxadiazol. Planejamos os cristais líquidos contendo tais conectores e cadeias alquílicas dodeciloxi (-OC12H25), obtendo materiais com estrutura geral: centro rígido + conectores + cadeias alcóxi. De acordo com a estrutura dos centros rígidos, preparamos treze mesógenos calamíticos (ácido tiazolo[5,4- d]tiazol-2,5-dicarboxílico), das quais seis apresentaram mesofases calamítica (comportamento esperados) e três apresentaram mesofases discóticas. O fotocromismo apresentado pelos sais de bipiridinas frente à radiação UVB nos permite sugerir aplicações como dosimetria desta radiação, presente na luz solar. As propriedades mesomórficas ainda estão em estudo. No entanto, conseguimos obter CL’s discóticos a temperatura ambiente e uma mesofase discótica nemática, bastante rara.
The study properties of organic materials has drawn attention due to its structural versatility and composition versatility, which can shape their physical and chemical properties. In this work, we prepared six rigid chromophores containing the heterocycle thiazolo[5,4-d] thiazole (Thz) as aromatic spacers, and pyridyl or carboxylic terminal groups. Hence, we have worked with two research lines: photo-electrochemistry for the pyridine derivatives and synthesis and characterization of liquid crystals (LCs). We investigated the photochemical properties and redox processes of the bipyridines X,X'-(thiazolo[5,4-d] thiazole-2,5-diyl)bis(pyridyl) (X,X' = 2,2 '; 3,3' or 4,4 '). In solution, these compounds showed acidochromic properties via photonand electrodissociantion of chlorinated solvents. Next, we prepare bipyridinium trifluoroacetate salts (viologens), which exhibited photochromic properties through electron transfer when exposed to UVB radiation. We used the carboxylic derivatives as rigid centers for the preparation of liquid crystals. We chose the carboxylate group as a synthetic precursor of organic connectors: esther, amide, and 1,3,5-oxadiazole. We plannned the liquid crystal containing these connectors and the alkoxy chains dodecyloxy (-OC12H25), obtaining materials with general structure: rigid center + connectors + alkoxy chains. According to the rigid center structure, we obtained thirteen calamitic (acid thiazolo [5,4-d] thiazole-2,5-dicarboxylic acid), six of which had mesophases calamítica (expected behavior) and three had discóticas mesophases. The photochromic presented by bipyridinium salts when exposed of UVB radiation allows suggest applications such as dosimetry of sunlight radiation. The mesomorphic properties are still under study. However, we obtained room temperatures discóticos LCs, as well as a nematic discótica mesophase which are quite rare.
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Aho, Joel. "Användning av 5D-BIM för planering av både industriellt och traditionellt byggande." Thesis, Luleå tekniska universitet, Institutionen för samhällsbyggnad och naturresurser, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:ltu:diva-77573.
Повний текст джерелаАнотація:
BIM – Building information modelling används idag av bl.a. arkitekter, konstruktörer,entreprenörer och fastighetsägare. BIM är ett verktyg där en 3D-modell av projektet kan användassom informationskälla.Genom att 3D-modellen innehåller mått/dimensioner, materialtyper, mm blir användandet avmodellen ett kraftfullt verktyg vid både kalkylering och produktionsplanering. Användandet avBIM-modeller vid dessa arbeten är ett relativt nytt arbetssätt där det finns väldigt få standarderoch beprövade metoder. För att använda sig av en BIM-modell vid kalkylering ochproduktionsplanering krävs dessutom en implementering av kalkyl- och planeringsprogram somstödjer användandet av BIM. Standarder och riktlinjer saknas också för själva utformandet avmodellen.Forskning visar att användandet av en BIM-modell vid mängdavtagning ochproduktionsplanering är både tidsbesparande och mer kostnadseffektivt än de traditionellametoderna där 2D-CAD-ritningar med tillhörande beskrivningar utgör de endainformationskällorna. Tidigare rapporter och examensarbeten har dessutom visat hur 5D-BIManvänds idag och hur det kan implementeras hos både industriella- och traditionelltplatsbyggande företag. 5D-BIM är ett arbetssätt där det utöver den tredimensionella modellenäven tillkommer tid och kostnad som dimension 4, och 5.Denna rapport syftar till att utvärdera de förutsättningar som krävs för implementering avarbetssättet 5D-BIM hos en entreprenör med både industriellt- och platsbyggande, samt utvärderavilka möjligheter och problem som en implementering av arbetssättet bidrar med. Användandetav BIM skiljer sig åt för industriella och platsbyggande entreprenörer. Författaren vill därförutvärdera vad som krävs för att arbetssättet ska kunna implementeras hos en entreprenör somproducerar hus med ett öppet byggsystem samt avgöra vad som krävs av själva BIM-modellen.En explorativ fallstudie har genomförts hos en delvis industriellt byggande småhustillverkare därarbetssättet 5D-BIM implementerats samt nuvarande arbetsgång genom projektering-,kalkylering till produktionsplanering kartlagts. Kartläggningen står som grund förimplementeringen av arbetssättet 5D-BIM där även utformandet av BIM-modellen utvärderats.Studien visar hur implementering av arbetssättet 5D-BIM kan gå till hos en entreprenör med bådeindustriellt- och traditionellt byggande utifrån den utförda kartläggningen, samt huranvändningen ökar förutsägbarheten i projekten.BIM – Building information modelling is used today by architects, structural engineers,contractors and property owners among others. BIM is a tool where a 3D-model of the projectcan be used as a source of information.When the 3D-model contains measurements/quantities and types of material it becomes apowerful tool when doing cost estimations/quantity takeoffs and production planning. The usageof BIM-models for these activities is a relatively new way of working and there are very fewstandards and proven methods. To have use of the BIM-model it also takes an implementation ofcost estimate- and planning programs that supports the use of BIM. Also, there are no standardsor guidelines for the configuration of the BIM-model.Research show that the use of BIM-models in quantity takeoff and production planning is bothtime-saving and more cost efficient then the use of the traditional ways where 2D-CAD drawingswith included descriptions is the only source of information. Earlier reports and master thesis’salso show how 5D-BIM is used today and how it can be implemented for companies with eitherindustrial- or more traditional concepts. 5D-BIM is a method where beyond the 3D-model, timeand cost are also included as dimensions 4, and 5.This report aims to evaluate under what conditions an implementation of 5D-BIM is possible fora contractor with a concept that includes both industrial- and traditional building, and alsoevaluate the possibilities and problems that occur during implementation. The use of BIM differsbetween industrial “off-site construction” and traditional “on site construction”. The author ofthis thesis therefor wants to study a company with a concept that includes both industrial andtraditional practices and also evaluate what information is requested in the BIM-model.An explorative case study has been conducted at a partially industrial contractor that produceshouses. The method 5D-BIM has been implemented and current workflow has been studied thrumodel configuration-, cost estimation to production planning. The study of the current workflowis the foundation for the implementation of 5D-BIM and the evaluation of § model configuration.The study shows how 5D-BIM as a method can be implemented for a company that has both onandoff site construction as a concept, and used to increase predictability in the projects.
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Langlois, Xavier. "Etude de l' expression et de l' adressage des récepteurs 5-HT 1A et 5 HT-1B/1D Bêta de la sérotonine à l' aide d' anticorps spécifiques." Paris 5, 1996. http://www.theses.fr/1996PA05P604.
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Becker, Guillaume. "Nouveaux concepts pour une imagerie fonctionnelle des récepteurs sérotoninergiques 5-HT1A et 5-HT6 lors de processus neurodégénératifs." Thesis, Lyon 1, 2013. http://www.theses.fr/2013LYO10270/document.
Повний текст джерелаАнотація:
L'imagerie TEP des récepteurs 5-HT1A a montré des modifications de la fixation hippocampique du radioligand antagoniste [18F]MPPF chez des patients souffrant de maladie d'Alzheimer (MA). Si les antagonistes se fixent indistinctement sur les récepteurs fonctionnels et non fonctionnels, les agonistes 5-HT1A, comme le ligand TEP [18F]F15599, ciblent les récepteurs fonctionnels (couplés aux protéines G). Notre objectif est de montrer que le ratio entre les récepteurs 5-HT1A couplés et non couplés varie avec l'évolution de la MA. Ainsi, l'analyse post-mortem d'hippocampes de patients à différents stades de la MA a montré une diminution significative du marquage au [18F]F15599 dès les stades précoces de la MA. Puis nous avons précisé le profil pharmacologique de trois agonistes 5-HT1A : le 8-OH-DPAT, le F13714 et le F15599. L'imagerie IRM fonctionnelle lors de stimuli pharmacologiques (IRMph) permet l'exploration de réseaux neuronaux activés par une molécule. Nous avons comparé chez le rat les cartes d'activation des trois agonistes 5-HT1A et d'un antagoniste, le MPPF. Chaque molécule présente un schéma d'activation spécifique, ouvrant le champ à un ciblage distinct, tant pour la thérapeutique que pour l'imagerie. Enfin, nous avons travaillé à la mise au point d'un radioligand TEP des récepteurs 5-HT6, également impliqués dans la MA. En collaboration avec une équipe de chimistes, nous avons évalué in vitro et in vivo trois radioligands 5-HT6 potentiels. Nous montrons que le radioligand [18F]2FNQ1P est le premier à montrer un ciblage spécifique des récepteurs 5-HT6 in vivoPET imaging using 5-HT1A radiotracers shows a modified expression of this serotonin receptor in the hippocampus of Alzheimer’s disease (AD) patients. However, these antagonists PET radioligands bind indiscriminately to the functional and the non-functional states of 5-HT1A receptors. The comparison of a PET agonist, binding selectively to the functional receptors, with a PET antagonist would therefore provide original information on 5-HT1A receptor impairment during AD. We found that [18F]F15599 in vitro binding decreased in dentate gyrus of AD patients. In contrast, binding of [18F]MPPF was unchanged. These results support the concept of functional PET imaging using agonist radiotracers in clinical studies. Then, we compared with functional MRI (PhMRI) the pharmacological profile of three 5-HT1A agonists (8-OH-DPAT, F13714 and F15599) and one antagonist (MPPF). PhMRI revealed that each molecule has its specific activation pattern, opening new ways in pharmacology or imaging. Finally, we developed in collaboration with chemists several 5-HT6 radioligand-candidates and evaluated their characteristics for PET imaging. Three radiotracers were evaluated in vitro and in vivo in rodent and feline models. We concluded that [18F]2FNQ1P is the first radioligand with suitable characteristics for PET imaging of 5-HT6 receptors, justifying further evaluations
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Hans, Joachim. "Isoprenoidbiosynthese in mykorrhizierten Maiswurzeln Klonierung, Charakterisierung und Lokalisierung einer 1-Desoxy-d-xylulose-5-phosphat-Reduktoisomerase (DXR) /." [S.l. : s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=97095106X.
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Gomez, Ana de Andres. "Investigation of 1-deoxy-D-xylulose 5-phosphate reductoisomerase as a potential novel target for antimicrobial development." Thesis, University of Bristol, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.424705.
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Conibear, Anne Claire. "Synthesis and evaluation of novel inhibitors of 1-Deoxy-D-xylolose-5-phosphate reductoisomerase as potential antimalarials." Thesis, Rhodes University, 2013. http://hdl.handle.net/10962/d1008282.
Повний текст джерелаАнотація:
Malaria continues to be an enormous health-threat in the developing world and the emergence of drug resistance has further compounded the problem. The parasite-specific enzyme, 1-deoxY-D-xylulose-S-phosphate reductoisomerase (DXR), has recently been validated as a promising antimalarial drug target. The present study comprises a combination of synthetic, physical organic, computer modelling and bioassay techniques directed towards the development of novel DXR inhibitors. A range of 2-heteroarylamino-2-oxoethyl- and 2- heteroarylamino-2-oxopropyl phosphonate esters and their corresponding phosphonic acid salts have been synthesised as analogues of the highly active DXR inhibitor, fosmidomycin. Treatment of the heteroarylamino precursors with chloroacetyl chloride or chloropropionyl chloride afforded chloroamide intermediates, Arbuzov reactions of which led to the corresponding diethyl phosphonate esters. Hydrolysis of the esters has been effected using bromotrimethylsilane. Twenty-four new compounds have been prepared and fully characterised using elemental (HRMS or combustion) and spectroscopic (1- and 2-D NMR and IR) analysis. A 31p NMR kinetic study has been carried out on the two-step silylation reaction involved in the hydrolysis of the phosphonate esters and has provided activation parameters for the reaction. The kinetic analysis was refined using a computational method to give an improved fit with the experimental data. Saturation transfer difference (STD) NMR analysis, computer-simulated docking and enzyme inhibition assays have been used to evaluate the enzyme-binding and -inhibition potential of the synthesised ligands. Minimal to moderate inhibitory activity has been observed and several structure-activity relationships have been identified. In silica exploration of the DXR active site has revealed an additional binding pocket and information on the topology of the active site has led to the de novo design of a new series of potential ligands.KMBT_363
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Liles, Amanda Gail. "The effects of resynchronization of estrus using the 5 d CO-Synch + CIDR system in beef heifers." Thesis, Virginia Tech, 2008. http://hdl.handle.net/10919/34684.
Повний текст джерелаАнотація:
Recent efforts have improved synchronization systems that facilitate timed insemination in beef cattle. However, synchronization systems utilizing a single fixed-time artificial insemination (FTAI) frequently result in 25-40% non-pregnant heifers. The purpose of this study was to determine the effectiveness and define economic parameters of a FTAI resynchronization protocol in beef heifers after synchronization using a 5d CO-Synch + CIDR system. Estrus was synchronized in crossbred heifers (n=176) using 5 d CO-Synch + CIDR with FTAI at 72 h. After the initial AI, open heifers received either resynchronization (RS) or natural service (NS) return service treatments. The RS treatment was diagnosed for pregnancy 29 d after the initial AI, and all open heifers were resynchronized using the 5 d CO-Synch + CIDR with FTAI at 72 h. Heifers diagnosed pregnant following initial AI received no further treatment. Heifers in the NS treatment were exposed to fertile bulls from d 14 to d 66 following initial AI. Return to estrus data were collected using the Heat Watch Estrus Alert System. Total AI pregnancies tended to be higher (P=0.07) for RS (69.7%) than NS (56.5%) heifers. Overall pregnancy rate was greater for NS (89.4%) than for RS (69.7%) at the end of the breeding season (P < 0.01). The cost of RS was $128.63 and for NS was $82.50 per pregnancy. The expected average calf value per heifer exposed was $195.84 for RS treatment and $357.62 for NS treatment. This difference was attributed to the increased number of open heifers in the RS treatment. The resynchronization of estrus after the initial FTAI yielded a limited number of pregnancies in the breeding season in this study. However, the resynchronization program also cost more per pregnancy. Further investigation into resynchronization should focus on both biological and economic impacts.Master of Science
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Goble, Jessica Leigh. "The druggable antimalarial target 1-deoxy-D-xylulose-5-phosphate reductoisomerase: purfication, kinetic characterization and inhibition studies." Thesis, Rhodes University, 2011. http://hdl.handle.net/10962/d1004008.
Повний текст джерелаАнотація:
Plasmodium falciparum 1–deoxy–D–xylulose–5 phosphatereductoisomerase (PfDXR) plays a role in isoprenoid biosynthesis in the malaria parasite and is absent in the human host, making this parasite enzyme an attractive target for antimalarial drug design. To characterize PfDXR, it is necessary to produce large quantities of the enzyme in a soluble and functional form. However, the over–production of malarial proteins in prokaryotic host systems often results in the formation of truncated proteins or insoluble protein aggregates. A heterologous expression system was developed for the production of active PfDXR using codon harmonization and tight control of expression in the presence of lac repressor. Yields of up to 2 mg/l of enzyme were reported using the optimised expression system, which is 8 to 10– fold greater than previously reported yields. The kinetic parameters Km, Vmax and kcat were determined for PfDXR; values reported in this study were consistent with those reported in the literature for other DXR enzymes. A three–dimensional model of the malarial drug target protein PfDXR was generated, and validated using structure–checking programs and protein docking studies. Structural and functional features unique to PfDXR were identified using the model and comparative sequence analyses with apicomplexan and non–apicomplexan DXR proteins. Residues Val44 and Asn45, essential for NADPH binding; and catalytic hatch residues Lys224 and Lys226, which are unique to the species of Plasmodium, were mutated to resemble those of E. coli DXR. Interestingly,these mutations resulted in significant reductions in substrate affinity, when compared to the unmutated PfDXR. Mutant enzymes PfDXR(VN43,44AG) and PfDXR(KK224,226NS) also demonstrated a decreased ability to turnover substrate by 4–fold and 2–fold respectively. This study indicates a difference in the role of the catalytic hatch of PfDXR with regards to the way in which it captures substrates. The study also highlights subtle differences in cofactor binding to PfDXR, compared with the well characterized EcDXR enzyme. The validated PfDXR model was also used to develop a novel efficient in silico screening method for potential tool compounds for use in the rational design of novel DXR inhibitors. Following in silico screening of 46 potential DXR inhibitors, a two–tiered in vitro screening approach was undertaken. DXR inhibition was assessed for the 46 novel compounds using an NADPH– ependant DXP enzyme inhibition assay and antimalarial potential was assessed using P.falciparum–infected erythrocyte growth assays. Select compounds were tested in human cells in order to determine whether they were toxic to the host. From the parallel in silico and in vitro drug screening, it was evident that only a single compound demonstrated reasonable potential binding to DXR (determined using in silico docking), inhibited DXR in vitro and inhibited P. falciparum growth, without being toxic to human cells. Its potential as a lead compound in antimalarial drug development is therefore feasible. Two outcomes were evident from this work. Firstly, analogues of known antimalarial natural products can be screened against malaria, which may then lead towards the rational design of novel compounds that are effective against a specific antimalarial drug target enzyme, such as PfDXR. Secondly, the rational design of novel compounds against a specific antimalarial drug target enzyme can be untaken by adopting a coupled in silico and in vitro approach to drug discovery.
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Naumann, Johann Gottlieb. "Vesper Nr. 5 D-Dur: Für Sopran, Alt, Chor, 2 Oboen, 2 Hörner in D, 2 Trompeten in D, Pauken Violinen, Violen, Basso continuo (Orgel, Violoncello, 2 Fagotte), 1788: Partitur." Ries & Erler, 2019. https://slub.qucosa.de/id/qucosa%3A35888.
Повний текст джерелаАнотація:
Johann Gottlieb Naumann ist die bedeutendste Persönlichkeit der Dresdner Hofmusik in der zweiten Hälfte des 18. Jahrhunderts. Er wurde am 17. April 1741 in Blasewitz bei Dresden geboren. Nach einer entbehrungsreichen Jugend erhielt er bereits als Sechzehnjähriger in Italien eine gründliche musikalische Ausbildung u. a. bei Giuseppe Tartini und Padre Martini. Nach seiner Rückkehr nach Dresden übertrug die hochgebildete Kurfürstin-Witwe Maria Antonia Walpurgis 1764 dem 23-jährigen das verantwortungsvolle Amt eines Kirchen-Compositeurs. [... aus der Einleitung]
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Siemen, Anna [Verfasser]. "Identifizierung und Charakterisierung neuartiger Oxidoreduktasen in Gluconobacter oxydans und Produktion des potentiellen Süßstoffes 5-Keto-D-Fruktose / Anna Siemen." Bonn : Universitäts- und Landesbibliothek Bonn, 2018. http://d-nb.info/1160594457/34.
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Munier, Mathilde. "Synthèse de prodrogues d'inhibiteurs de la 1-désoxy-D-xylulose 5-phosphate réductoisomérase (DXR) : des agents antituberculeux potentiels." Thesis, Strasbourg, 2016. http://www.theses.fr/2016STRAF016.
Повний текст джерелаАнотація:
De nos jours la tuberculose est une des maladies les plus meurtrières au monde. Un problème majeur est que l’agent pathogène responsable de cette maladie (Mycobacterium tuberculosis) a développé des mécanismes de résistances envers les médicaments actuels. Il devient donc urgent de trouver d’autres cibles pour développer de nouveaux antituberculeux. La biosynthèse des isoprénoïdes pourrait en être une. Les précurseurs biologiques de tous les isoprénoïdes sont l’IPP et le DMAPP qui sont synthétisés selon deux voies. La voie du mévalonate, présente chez l’Homme et la voie du méthylérythritol phosphate (MEP) laquelle est présente chez M. tuberculosis et absente chez l’homme. La fosmidomycine et la fosfoxacine, deux inhibiteurs de la désoxyxylulose phosphate réductoisomérase (DXR), deuxième enzyme de la voie du MEP ne permet pas d’inhiber la croissance de la mycobactérie. Cela est dû à l’absence de pénétration de ces composés polaires au sein de la bactérie. Pour pallier à ces problèmes de biodisponibilité, nous avons synthétisé des prodrogues lipophiles de type cycloSaligényle et arylphosphoramidate d’inhibiteurs de la DXR. Certains composés sont inhibent la croissance d’une mycobactérie non-pathogène, Mycobacterium smegmatisToday, tuberculosis is one of most murderous infectious diseases in the world. This disease is caused by the mycobacterium : Mycobacterium tuberculosis which is becoming more and more resistant towards antitubercular drugs. Therefore, it is urgent to find inovative targets for the development of new antitubercular drugs. The biosynthesis of isoprenoids represents such a target. The biological precursors of all isoprenoids are IPP and DMAPP which are synthesized via two pathways the mevalonate pathway, which is present in human and the methylerythritol phosphate (MEP) pathway which is present in M. tuberculosis. but absent in human. Fosmidomycin and fosfoxacine, two natural inhibitors of the deoxyxylulose phosphate reductoisomerase (DXR), the second enzyme of MEP pathway, but they do not affect the growth of Mycobacterium tuberculosis cells, due to a lack of uptake of the polar drugs by the bacteria. To overcome this absence of the mycobacterial cell watll crossing of these compounds, we synthesized lipophilic cycloSaligenyl and arylphosphoramidate prodrugs of DXR inhibitors. Some compounds inhibit the growth of Mycobacterium smegmatis, a non-pathogenic model of mycobacterium
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Gallais-Barré, Catherine. "Conception d' outils moléculaires pour la caractérisation du récepteur 5-HT3 : synthèses de sondes fluorescentes et/ou irréversibles." Paris 5, 1995. http://www.theses.fr/1995PA05P629.
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Mutorwa, Marius Kudumo. "Synthesis of novel inhibitors of 1-Deoxy-D-xylulose-5-phosphate reductoisomerase as potential anti-malarial lead compounds." Thesis, Rhodes University, 2011. http://hdl.handle.net/10962/d1005037.
Повний текст джерелаАнотація:
This research has focused on the development of novel substrate mimics as potential DXR inhibitors of 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR), an essential enzyme in the mevalonate-independent pathway for the biosynthesis of isoprenoids in Plasmodium falciparum. DXR mediates the isomerisation and reduction of 1-deoxy-D-xylulose-5-phosphate (DOXP) into 2C-methyl-D-erithrytol 4-phosphate (MEP) and has been validated as an attractive target for the development of novel anti-malarial chemotherapeutic agents. Reaction of various amines with specially prepared 4-phosphonated crotonic acid in the presence of the peptide coupling reagent, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), has afforded a series of amido-phosphonate esters in moderate to good yields (48% - 73%) which, using a RuCl₃/CeCl₃/NaIO₄ catalyst system, have been dihydroxylated to furnish the dihydroxy-amido phosphonate ester pro-drugs; subsequent hydrolysis under microwave irradiation has afforded the corresponding phosphonic acids. A second series of potential inhibitors viz., 3-substituted aniline-derived phosphonate esters, their corresponding phosphonic acids and mono-sodium salts, have also been successfully synthesised. In these compounds, the essential functional groups are separated by one, two, three or four methylene groups, Deprotonation of the 3-substituted aniline substrates, followed by reaction with the appropriate ω-chloroalkanoyl chloride produced the ω-chloroamide intermediates, which were subjected to the Michaelis-Arbuzov reaction to afford the diethyl phosphonate esters in moderate to good yields (48% - 74%). Microwave-assisted TMSBrmediated cleavage of the phosphonate esters furnished the phosphonic acids, neutralisation of which afforded the mono-sodium salts. Furan-derived phosphate esters and phosphonic acids have been prepared as conformationally-restricted DOXP analogues. Functionalization at C-5 of the trityl-protected furan was achieved using the Vilsmeier-Haack formylation and Friedel-Crafts acylation reactions and, following de-tritylation, phosphorylation and oximation, using hydroxylamine hydrochloride, the novel oxime derivatives have been isolated as a third series of potential DXR inhibitors in very good yields (87% - 96%). Finally, in order to exploit an additional binding pocket in the PƒDXR active site, a series of N-benzylated phosphoramidic derivatives were obtained in seven steps from the starting material, diethyl phosphoramidate. The known inhibitors, fosmidomycin and its acetyl derivative FR900098, were also successfully synthesised as standards for STD-NMR binding and inhibition assays. In all, over 200 compounds (136 novel) have been prepared and appropriately characterised using 1-and 2-D NMR and IR spectroscopic analysis and, where necessary, HRMS or combustion analysis. Saturation Transfer Difference (STD) protein-NMR experiments, undertaken using selected compounds, have revealed binding of most of the ligands examined to EcDXR. Computersimulated docking studies have also been used to explore the preferred ligand-binding conformations and interactions between the ligands and essential DXR active-site residues, while DXR-enzyme inhibition assays of selected synthesised ligands have revealed certain patterns of inhibitory activity.
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Dummer, Luana Alves. "Clonagem e expressão em Pichia pastoris da forma truncada da glicoproteína D (gD) de Herpesvírus Bovino tipo 5." Universidade Federal de Pelotas, 2008. http://guaiaca.ufpel.edu.br/handle/123456789/1258.
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Previous issue date: 2008-06-12Outbreaks of fatal meningoencephalitis caused by Bovine Herpesvirus type 5 (BoHV-5) cause important economic losses in national trade of bovine beef. Commercial vaccines developed against Bovine Herpesvirus type 1 can protect cattle of neurological disease caused by BoHV-5. These cross-reactions are due to its genetic and antigenic similarities of both BoHV-1 and 5. However, these vaccines can not prevent latent infection of BoHV-5, even viral spread to healthy animals. This way, new vaccines strategies are based on envelope glycoproteins and are focusing safety, economic viability and on prevention of BoHV-5 latency and spread. This glycoprotein acts in initial steps of viral infection and glycoprotein D has drawn the attention in studies carried out with BoHV-1 and other homologous herpesvirus. The gD acts on viral membrane fusion with permissive cells through glycoproteins and host receptors interactions, so it is essential for viral entry. A vaccine that is capable to stimulate specific humoral and cellular immunity against BoHV-5 must be developed. The aim of this work was the production of a recombinant truncated form of gD of BoHV-5 in yeast Pichia pastoris and its antigenicity and immunogenicity evaluation. Data show that yeast P. pastoris can express the truncated form of BoHV-5 gD to the supernatant due to its secretion of ~190mg/L of recombinant protein, simplifying protein purification. The recombinant protein was successfully recognized by antibodies of animals immunized with BoHV-5, suggesting its antigenicity and immunogenicity and that native protein characteristic are conserved. The data presented herein allow the design of future studies aiming at expression optimization and further immunogenicity evaluation, as well as its capacity to neutralize the virus in biological models and on cattle.
Surtos de meningoencefalites fatais causadas pelo Herpesvírus Bovino tipo 5 (BoHV-5) ocasionam importantes perdas econômicas no comércio nacional de carne bovina. Vacinas comerciais destinadas ao Herpesvírus Bovino tipo 1 são capazes de impedir o aparecimento de sintomatologia clínica do BoHV-5. Estas reações cruzadas se devem a existência de semelhanças genéticas e antigênicas existentes entre ambos os vírus. No entanto, estas vacinas não impedem o estabelecimento da infecção latente e a disseminação do BoHV-5 para animais não imunizados. Desta forma, estratégias que visem à produção de vacinas seguras, economicamente viáveis e que possam ser capazes de impedir a latência do BoHV-5 e sua disseminação estão focadas para glicoproteínas localizadas no envelope viral e que atuam nas etapas iniciais da infecção. Dentre estas, a glicoproteína D tem se destacado em estudos realizados com BoHV-1 e outros herpesvírus homólogos. A gD atua na fusão do envelope viral com a membrana da célula permissiva no hospedeiro através de interações com receptores celulares e com outras glicoproteínas virais, sendo essencial para a entrada do capsídeo na célula. Assim, uma vacina que seja capaz de estimular respostas humorais e celulares contra esta glicoproteína deve ser desenvolvida. Os objetivos deste trabalho foram à produção da forma truncada da gD do BoHV-5 em levedura Pichia pastoris e a avaliação desta quanto a sua antigenicidade e imunogenicidade. Os resultados demonstram que a Pichia pastoris expressou a forma truncada da gD de BoHV-5 secretando para o meio de cultivo ~190mg/L da proteína recombinante, facilitando a purificação da mesma. Testada quanto a sua a sua antigenicidade e imunogenicidade, a proteína recombinante foi reconhecida por anticorpos de animais imunizados com o BoHV-5, sugerindo que características da proteína nativa foram conservadas na proteína recombinante. Os dados apresentados irão permitir o desenvolvimento de estudos 6 futuros com o objetivo de aperfeiçoar a expressão da proteína recombinante e avaliar a sua capacidade de neutralizar o vírus na espécie-alvo.
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Shamim, Anwar. "Funcionalização de 3,4,6-tri-O-acetil-D-glucal via click chemistry e reações de acoplamento cruzado catalizado por paládio." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/46/46136/tde-22112017-143637/.
Повний текст джерелаАнотація:
A funcionalização de 3,4,6-tri-O-acetil-D-glucal foi realizada utilizando reações de acoplamento cruzado (Sonogashira e Stille), ciclo-adições de azida-alcino (Click chemistry) e ciclização nucleófila promovida por eletrófilo. Utilizando estas reações juntamente com as já referidas transformações de grupos funcionais e reações de rearranjo de Ferrier, as bibliotecas de compostos à base de glucal foram sintetizadas e observadas em algumas moléculas fluorescência e outras foram disponibilizadas para avaliação de atividade biológica. Na primeira parte, foram sintetizadas bibliotecas de derivados de bis- e tris-triazolil-glicosila a partir de 3,4,6-tri-O-acetil-D-glucal utilizando as reações acima mencionadas. A segunda parte deste trabalho consiste em sintetizar uma biblioteca de derivados glucal de 2-alquinilo usando um acoplamento de Sonogashira livre de cobre e ligante, seguido por aplicações sintéticas destes alquinos glucais. A hidrostanação regioselectiva catalisada por paládio destes glucanos 2-alquinilo foi realizada utilizando hidreto de tributilestanho para gerar uma biblioteca de derivados estanil regioisoméricos de glucal. Além disso, estes derivados de 2-alquinil-glucal sintetizados na primeira parte também foram utilizados na ciclização nucleofílica 5-endo-dig promovida por eletrófilos para proporcionar derivados de glucal bicíclicos. Na parte final, os derivados de estanho de glucal foram utilizados para sintetizar bibliotecas de derivados de 2-alcenil glucal substituído. Esta parte inclui também transformações de grupos funcionais e acoplamentos cruzados (Stille e Sonogashira), bem como click chemistry para gerar bibliotecas de derivados de 2-alquenil-D-glucal alquinilo e triazolilo substituídos. Na maioria dos casos os produtos foram obtidos em rendimentos muito bons a excelentes que foram analisados utilizando RMN, Infra vermehlo, espectrometria de massas de alta resolução e outras técnicas analíticas quando aplicável.Functionalization of 3,4,6-tri-O-acetyl-D-glucal has been performed using cross-coupling (Sonogashira and Stille) reactions, azide-alkyne cycloadditions (Click chemistry) and electrophile-promoted nucleophilic alkyne cyclizations. Using these reactions along with the already reported functional group transformations (FGT) and Ferrier rearrangement reactions, libraries of glucal-based compounds were synthesized with members of characteristic photophysical and potential biological properties. In the first part, the synthesis of libraries of bis- and tris-triazolyl glycosyl derivatives is described starting from 3,4,6-tri-O-acetyl-D-glucal using the above-mentioned reactions. In the second part of this work, the synthesis of a library of 2-alkynyl glucal derivatives using a copper and ligand-free Sonogashira coupling, followed by synthetic applications of these glucal alkynes is reported. Palladium-catalyzed regioselective hydrostannation of these 2-alkynyl glucals was performed using tributyltin hydride to generate a library of regioisomeric stannyl derivatives of glucal. Moreover, these 2-alkynyl glucal derivatives synthesized in the first part were also used in electrophile-promoted nucleophilic 5-endo-dig cyclization to afford bicyclic glucal derivatives. In the final part, the use of stannyl derivatives of glucal to synthesize libraries of substituted 2-alkenyl glucal derivatives is described. This part also includes certain functional group transformations and cross-couplings (Stille and Sonogashira) as well as click chemistry to generate libraries of alkynyl and triazolyl substituted 2-alkenyl-D-glucal derivatives. In most of the cases, the products were obtained in very good to excellent yields and were analyzed using 1H NMR, 13C NMR, FTIR, HRMS, and other analytic techniques where applicable