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1
Chen, Ron An-Jung. "Characterisation of the B14 protein in vaccinia virus strain Western Reserve." Thesis, Imperial College London, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.428719.
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McCoy, Laura Ellen. "Vaccinia virus protein B14, an inhibitor of NF-κB activation, and its counterpart in MVA." Thesis, Imperial College London, 2010. http://hdl.handle.net/10044/1/5590.
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Vaccinia virus (VACV) encodes multiple proteins which modulate NF-[kappa]B activation to evade the host immune response. One example is B14, a virulence factor that reduces NF-[kappa]B activation via interaction with IKK [Beta]. B14 has orthologues in many VACV strains, including modified virus Ankara (MVA), which lacks many of the immunomodulators present in other VACV strains. Here, the MVA counterpart of B14, protein 183, was characterised. 183R was both removed from MVA and inserted into the B14R locus of a VACV strain Western Reserve (WR) lacking B14R, but in each case there was no change of phenotype. Protein 183 shares 95 % amino acid identity with B14 but, unlike B14, was unstable in eukaryotic cells, unless protein degradation was inhibited. Protein 183 did not inhibit NF-[kappa] B activation in response to cytokine stimulation, as does B14, nor did it restore the virulence phenotype of WR lacking B14R back to wild type. Therefore, the mutations incurred by 183 during the derivation of MVA have rendered the protein non-functional. However, other MVA immunomodulators remain to be characterised and this thesis describes a bacterial artificial chromosome (BAC) system that may facilitate the improvement of MVA in its role as a vaccine vector. To further characterise VACV modulation of NF-[kappa] B, a VACV WR strain was constructed lacking B14 and another VACV modulator of NF-[kappa]B, WR A49. Initial characterisation showed no change with this mutant virus in replication or spread. The effect of the B14 on NF-[kappa]B was further characterised by studying the B14-IKK [Beta] interaction using IKK[Beta] and B14 mutants. Residues 300 to 480 of IKK [Beta] were shown to be required for the interaction and a mutant encompassing this region co-purified to a degree with B14 when expressed in E. coli. In addition, mutagenesis showed that B14 residue F130 is required for the interaction of the two proteins.
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Ribeiro, Maria Carolina de Oliveira. "Caracterização do Pediococcus acidilactic b14 quanto às propriedades probióticas e sua associação com lactobacillus acidophilus ATCC 4356 com aplicação em sobremesa com soja aerada potencialmente simbiótica." reponame:Repositório Institucional da UFPR, 2013. http://hdl.handle.net/1884/30592.
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Resumo: As matérias-primas de origem vegetal podem representar fontes seguras de bactérias ácido láticas com propriedades particulares. Portanto, o objetivo deste estudo foi caracterizar quanto ao potencial probiótico à bactéria ácido lática Pediococcus acidilactici B14, isolada de matéria-prima de origem vegetal, para empregar em cultura associada no desenvolvimento de sobremesa com soja aerada, potencialmente simbiótica. Inicialmente, foram empregadas 10 fontes de matériasprimas vegetais para o isolamento, dos 63 isolados obtidos apenas 13 foram selecionados como bactérias ácido láticas. Somente 4 das culturas selecionadas não foram classificadas presuntivamente como enterococos e não apresentaram atividade hemolítica. Estas cepas foram avaliadas quanto a vários aspectos, de forma a verificar a capacidade de utilização como cultura starter no processamento de alimentos. Estes cultivos foram submetidos à identificação molecular obtendo índice de confirmação de 96,35, 82,4, 93,0% como Pediococcus acidilactici, apenas para uma estirpe a identificação não foi conclusiva quanto à espécie. A espécie de Pediococcus acidilactici que apresentou maior índice de confirmação foi obtida do fruto do baru (Dipteryx alata), esta cepa foi avaliada quanto ao seu potencial probiótico apresentando resultados como tolerância aos antimicrobianos cefalexina, cefotaxima, neomicina, penicilina G e vancomicina e inibição de alguns patógenos. A capacidade de adesão in vitro foi de 64 bactérias/ 100 células HRT-18 de adenocarcinoma humano e ao ser submetida ao trânsito gastrointestinal simulado in vitro, apresentou 65,82 e 97,45% de sobrevivência quando o suco gástrico foi mantido em pH 2,0 e 4,0, respectivamente. Quando associada com o Lactobacillus acidophilus ATCC 4356, com o qual não apresentou antagonismo, obteve taxa máxima de crescimento de 0,513 h-1 em 10 h e 0,416 g.L-1.h-1 de produtividade em ácido lático em 48 h de fermentação, o índice de sobrevivência nas mesmas condições simuladas do trato gastrointestinal foi de 57,28% (pH 2,0) e 92,39% (pH 4,0). Esta cultura associada foi considerada potencialmente probiótica e quando adicionada em sobremesa com soja aerada prebiótica, como matriz alimentar, originou um produto potencialmente simbiótico. A sobremesa foi submetida ao armazenamento refrigerado (4 1°C) por 28 dias, sendo avaliada a cada 7 dias. Durante este período de estocagem apresentou população celular de 9,82 a 9,26 log UFC.120g-1, estando o produto adequado a legislação vigente. A presença da matriz alimentar promoveu um aumento de 10,00 e 5,68% na viabilidade celular da cultura associada, em comparação a sua forma livre, quando submetida ao trânsito gastrointestinal nas condições de pH 2,0 e 4,0, respectivamente. As sobremesas de 1 e 28 dias de armazenamento se apresentaram adequadas, segundo a legislação vigente, quanto ao aspecto sanitário e sem diferença significativa para o atributo acidez, a aceitabilidade e preferência. O custo final de fabricação estimado foi de R$ 2,12 para a porção de 120 g de sobremesa. Embora o setor de alimentos funcionais apresente forte tendência de crescimento, no Brasil e no mundo, o desenvolvimento e a inovação destes produtos estão atrelados a escolha ideal do par linhagem probiótica e matriz alimentar, seleção esta, que demanda tempo e exaustiva investigação.
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Svangren, Henrik. "Konceptstudie av kassadisk B10/B11." Thesis, Jönköping University, JTH, Mechanical Engineering, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:hj:diva-942.
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This master’s thesis report is a summary of the analysis performed together with ITAB Shop Concept located in Jönköping, Sweden. As a last element of the Master’s program at the School of Engineering, this 20 point level D thesis project has been the final work to bring my education to an end.
ITAB Shop Concept expressed an aspiration that the Shop Counter Program B10/B11 should undergo an analysis to point out and possibly lead to improvement.
Through interviews and data collection proposals for possible improvements has been drawn up and the analysis points out current deficiencies. By following the idea generation, proposals to solutions for every individual problem is presented. These proposals are weighted and compared to specified requirements.
The result is built up through a number of changes in the Shop Counter Program, partly by suggestions on reduction of part, but also how the Shop Counter can be re-designed.
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Sánchez, Huamaní Juan Pablo. "Eficacia analgésica de diclofenaco más vitaminas b1, b6 y b12 en comparación a sólo diclofenaco en cirugía de tercera molar inferior." Bachelor's thesis, Universidad Nacional Mayor de San Marcos, 2015. https://hdl.handle.net/20.500.12672/4541.
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Esta tesis está basada en un ensayo clínico, simple-ciego y no aleatorizado, realizado en el servicio de Cirugía Oral y Maxilofacial del Hospital Nacional Hipólito Unanue, cuyo objetivo fue determinar si la terapia con diclofenaco más vitaminas B es superior a la terapia con sólo diclofenaco en pacientes sometidos a cirugía electiva de tercera molar inferior. Se formaron 2 grupos, un grupo recibió diclofenaco más vitaminas B y el otro diclofenaco solo. La variable principal fue la intensidad de dolor medida luego de 1, 3, 6, 9, 12 y 24 horas de finalizada la cirugía mediante una escala gráfica verbal del 0-100; las variables secundarias fueron el tiempo para analgesia de rescate y la cantidad de analgésicos consumidos en el postoperatorio. Treinta pacientes completaron el estudio, quince de ellos recibieron diclofenaco (75 mg) más una mezcla de vitaminas B (B1: 100 mg, B6: 100 mg y B12: 10 mg) y los otros quince solamente diclofenaco (75 mg). Ambas terapias fueron administradas por vía intramuscular al finalizar la cirugía. Los resultados mostraron que la adición de vitaminas B al diclofenaco mejoró la eficacia analgésica del diclofenaco en la variable principal pero no de manera estadísticamente significativa (p > 0.05). Palabras clave: diclofenaco - vitaminas b - cirugía dental - tercera molar impactada--- This thesis is based on a single-blind, non-randomized clinical trial which took place in the oral and maxillofacial surgery service of the Hipólito Unanue National Hospital, of which objective was to determine if the therapy using diclofenac plus B vitamins is better than the therapy using only diclofenac in patients subjected to elective surgery of inferior third molar. Two groups were formed, a group received diclofenac plus B vitamins and the other group received diclofenac only. The main variable was the intensity of pain measured after 1, 3, 6, 9, 12 and 24 hours the surgery had finished using a verbal graphic scale (0-100); the secondary variables were the time for rescue analgesics consumption and the amount of rescue analgesics taken in the postoperative period. Thirty patients completed the study, fifteen of them received diclofenac (75 mg) plus B vitamins (B1: 100 mg, B6: 100 mg and B12: 10 mg) and other fifteen patients received only diclofenac (75 mg). Both therapies were administered by intramuscular route once the surgery was finished. The results showed that by adding B vitamins to diclofenac improved the analgesic effectiveness of diclofenac in the main variable but there were no statistically significant differences. Keywords: diclofenac – b vitamins – dental surgery – impacted third molar
Tesis
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Alfaro, Carbajal Cesar Alberto. "Consulting report – Agencia B12." Master's thesis, Pontificia Universidad Católica del Perú, 2019. http://hdl.handle.net/20.500.12404/15246.
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Agencia B12 is a Spanish company with operations in Mexico, Peru and Spain.
Agencia B12 develops its operations mainly in digital marketing and call service center. This
type of services offered by the firm are operated in the telecommunications companies (such
as Movistar, Claro, Bitel and Entel Peru), Agencia B12 works with the main companies in the
telecommunication sector, however, Agencia B12 are currently working with some
companies which are from other induastrias such as Direct tv and Banco Pichincha. The
current purpose of Agencia B12 is to diversify its portfolio of services in order to acquire new
sources of revenues. The new projects that Agencia B12 wishes to develop are due to its
client portfolio being strongly linked to the telecommunications industry, in response to this
situation Agencia B12 wishes to launch Digital collection in order to expand its customer
portfolio, venturing into the collection market, working with new clients, in this case the
financial entities. Although, the project will initially be launched as a prototype in Peru, the
desire of Agencia B12 is to expand this service to other branches.Agencia B12 es una subsidiaria de un grupo español con operaciones en México, Perú y España. Agencia B12 desarrolla sus operaciones principalmente en marketing digital y servicio de llamadas. Este tipo de servicios ofrecidos por la firma son operados en las compañías de telecomunicaciones (como Movistar, Claro, Bitel and Entel Perú), Agencia B12 trabaja en colaboración con las principales compañías en sector de telecomunicaciones, sin embargo, actualmente se encuentra trabajando con algunas compañías que son de otras industrias como Direct tv y el Banco Pichincha. El actual propósito de Agencia B12 es diversificar su portafolio de servicios con la finalidad de poder adquirir nuevas fuentes de ingreso. Los nuevos proyectos que Agencia B12 desea desarrollar son debido a que su portafolio de clientes está fuertemente ligado a la industria de telecomunicaciones, en respuesta a esta situación Agencia B12 desea lanzar Digital collection con el objetivo de expandir su portafolio de clientes, aventurándose en el mercado cobranza, trabajando con nuevos clientes, en este caso las entidades financieras. Si bien, el proyecto inicialmente será lanzado como prototipo en Perú, el deseo de Agencia B12 es expandir este servicio hacia otras sucursales.
Tesis
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Oliveira, Gersilene Valente de. "Vitaminas B1, B6, B12 e Complexo B na prevenÃÃo da discinesia orofacial induzida por haloperidol em ratos: avaliaÃÃo comportamental e mecanismos associados." Universidade Federal do CearÃ, 2015. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=16133.
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CoordenaÃÃo de AperfeÃoamento de Pessoal de NÃvel SuperiorA Discinesia tardia (DT) à caracterizada por movimentos involuntÃrios, principalmente na parte inferior da face, prÃximos da boca, com espasmos que podem ser leves ou severos. à uma alteraÃÃo motora grave relacionada, mas nÃo restrita à terapia antipsicÃtica. Tratamentos com antipsicÃticos principalmente os da classe dos tÃpicos, como o haloperidol (HAL) aumentam os riscos de DT. A fisiopatologia da DT à associada a um desequilÃbrio em sistemas de neurotransmissÃo, dentre eles dopaminÃrgico e colinÃrgico, bem como com desequilÃbrio oxidativo, principalmente em Ãreas cerebrais relacionadas ao controle do movimento, como o corpo estriado. As vitaminas (vit.) B, por sua vez, apresentam efeitos antioxidantes sendo cofatores para enzimas relacionadas à sÃntese de neurotransmissores. Neste contexto, o presente trabalho teve como objetivo determinar os efeitos preventivos das vit. B1, B6, B12 ou Complexo B na discinesia orofacial (DO) induzida por HAL em ratos. Foram utilizados ratos Wistar machos tratados por via intraperitoneal com HAL (1 mg/kg, i.p.) por 21 dias ou concomitantemente com HAL e as vit. B1 (60 mg/kg), B6 (60 mg/kg) ou B12 (0,6 mg/kg) por via subcutÃnea, sozinhas ou em associaÃÃo (complexo B). O complexo B consistiu na mistura das 3 vitaminas em iguais proporÃÃes. Um grupo de animais foi administrado clozapina (25 mg/kg), um antipsicÃtico atÃpico nÃo relacionado ao desenvolvimento de DO. Os testes comportamentais foram realizados apÃs 30 minutos no 1Â, 7 e 21 dias de administraÃÃo das fÃrmacos e consistiram na determinaÃÃo da atividade locomotora, catalepsia e movimentos de mastigaÃÃo no vazio. No 21 dia os animais foram sacrificados e retiradas Ãreas cerebrais para as anÃlises neuroquÃmicas e de expressÃo para tirosina hidroxilase (TH), receptores dopaminÃrgicos D1 e D2 e receptor muscarÃnico M1. Os resultados mostraram que o HAL aumentou o tempo de catalepsia no dia 7 e causou DO no dia 21. A administraÃÃo das vit. B (B1: B6: B12) sozinhas ou em associaÃÃo, juntamente com HAL, preveniu o desenvolvimento de DO e em menor extensÃo da catalepsia. O efeito preventivo das vit. B foi acompanhado por restauraÃÃo dos nÃveis de glutationa reduzida (GSH) e peroxidaÃÃo lipÃdica. AlÃm dos efeitos antioxidantes, as vit. B aumentaram a atividade da enzima acetilcolinesterase (AChE) em todas as Ãreas cerebrais estudadas, com o incremento mÃximo de atividade observada no hipocampo de animais co-tratados com vit. B12 e coquetel de vit. B. A clozapina nÃo induziu DO e aumentou a atividade AChE semelhante para os grupos co-administrados com vit. B e HAL. A anÃlise da expressÃo de receptores e enzimas relacionadas à sÃntese de neurotransmissores no corpo estriado por PCR-RT revelou que o HAL foi capaz de aumentar a expressÃo de receptores dopaminÃrgicos D1 e D2 e reduzir a expressÃo dos receptores muscarÃnicos M1. A expressÃo da tirosina hidroxilase (TH), passo limitante para a sÃntese de dopamina, se apresentou reduzida pelo HAL. Os dados sugerem que as vitamina do complexo B sÃo capazes de prevenir as alteraÃÃes induzidas pelo HAL apresentando, portanto, um papel promissor na prevenÃÃo de DO associada ao uso desta fÃrmaco.
Tardive dyskinesia (TD) is characterized by involuntary movements, mostly at lower face, near the mouth, with convulsion that can be light or hard. Is one severe disorder related, but restricted the antipsychotic therapy. Antipsychotic treatments above all the class of typical, like haloperidol (HAL) increase the risk of TD. The pathophysiology of TD is associated to a instability in neurotransmission system, such as dopaminergic and cholinergic, among others, as well as with oxidative instability mainly in brain areas related to the control of movement, as the striatum. B vitamins, in turn, show antioxidants effect and are cofactors to enzymes related to the synthesis of neurotransmitters. In this context, the present study aimed to determine the preventive effects of B1, B6, B12 vitamins or B complex against orofacial dyskinesia (OD) induced by HAL in rats. To do this male Wistar rats were intraperitoneally administered HAL (1 mg/kg, i.p.) for 21 days or concomitantly received HAL, B1 (60 mg/kg), B6 (60 mg/kg) or B12 (0,6 mg/kg) vitamin subcutaneously alone or in association. B complex consisted in the mix of 3 vitamins in equal proportions. One group of animals was administered with clozapine (25 mg/kg), an atypical antipsychotic not related to the development of OD. Behavioral tests were performed at the 1st, 7th and 21st days of drugs administration. The behavioral tests performed were locomotor activity, catalepsy and chewing vacuous movements. At 21st day the animals were sacrificed and had their brain areas dissected for neurochemical analysis. The results showed that HAL increased catalepsy time at 7th day and OD at 21st day. Administration of B vitamins (B1:B6:B12) alone or in association, together with HAL, prevented the development of OD and in a lower extension, catalepsy. Preventive effect of B vitamins was accompanied by restoration of the levels of reduced glutathione (GSH) and lipid peroxidation. Beyond the antioxidant effects, B vitamins increased the activity of the enzyme acetylcholinesterase (AChE) in all brain areas studied, with the maximum increase of activity observed in the hippocampus of animals co-administered with B12 vitamins and B vitamins cocktail. Clozapine did not induce OD and increase in the activity of AChE. Analysis of the expression of receptors and enzymes related to the synthesis of neurotransmitters in striatum by PCR-RT revealed that HAL increased the expression of the dopaminergic receptors D1 and D2 and reduce an expression of the muscarinic receptors M1. Haloperidol decreased the expression of tyrosine hydroxylase (TH), a limiting step for the synthesis of dopamine. Taken together the results suggest that B vitamins prevented changes induced by HAL, presenting thus a promising role as a preventive approach against HAL-induced OD.
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Oliveira, Gersilene Valente de. "Vitaminas B1, B6, B12 e Complexo B na prevenção da discinesia orofacial induzida por haloperidol em ratos : avaliação comportamental e mecanismos associados." reponame:Repositório Institucional da UFC, 2015. http://www.repositorio.ufc.br/handle/riufc/15726.
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OLIVEIRA, Gersilene Valente de. Vitaminas B1, B6, B12 e Complexo B na prevenção da discinesia orofacial induzida por haloperidol em ratos: avaliação comportamental e mecanismos associados. 2015. 120 f. Tese (Doutorado em Farmacologia) – Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2015.Submitted by denise santos (denise.santos@ufc.br) on 2016-03-23T11:46:26Z No. of bitstreams: 1 2015_tese_gvoliveira.pdf: 1674290 bytes, checksum: 228729dd06081b0ef7e89c28e47625d3 (MD5)
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Tardive dyskinesia (TD) is characterized by involuntary movements, mostly at lower face, near the mouth, with convulsion that can be light or hard. Is one severe disorder related, but restricted the antipsychotic therapy. Antipsychotic treatments above all the class of typical, like haloperidol (HAL) increase the risk of TD. The pathophysiology of TD is associated to a instability in neurotransmission system, such as dopaminergic and cholinergic, among others, as well as with oxidative instability mainly in brain areas related to the control of movement, as the striatum. B vitamins, in turn, show antioxidants effect and are cofactors to enzymes related to the synthesis of neurotransmitters. In this context, the present study aimed to determine the preventive effects of B1, B6, B12 vitamins or B complex against orofacial dyskinesia (OD) induced by HAL in rats. To do this male Wistar rats were intraperitoneally administered HAL (1 mg/kg, i.p.) for 21 days or concomitantly received HAL, B1 (60 mg/kg), B6 (60 mg/kg) or B12 (0,6 mg/kg) vitamin subcutaneously alone or in association. B complex consisted in the mix of 3 vitamins in equal proportions. One group of animals was administered with clozapine (25 mg/kg), an atypical antipsychotic not related to the development of OD. Behavioral tests were performed at the 1st, 7th and 21st days of drugs administration. The behavioral tests performed were locomotor activity, catalepsy and chewing vacuous movements. At 21st day the animals were sacrificed and had their brain areas dissected for neurochemical analysis. The results showed that HAL increased catalepsy time at 7th day and OD at 21st day. Administration of B vitamins (B1:B6:B12) alone or in association, together with HAL, prevented the development of OD and in a lower extension, catalepsy. Preventive effect of B vitamins was accompanied by restoration of the levels of reduced glutathione (GSH) and lipid peroxidation. Beyond the antioxidant effects, B vitamins increased the activity of the enzyme acetylcholinesterase (AChE) in all brain areas studied, with the maximum increase of activity observed in the hippocampus of animals co-administered with B12 vitamins and B vitamins cocktail. Clozapine did not induce OD and increase in the activity of AChE. Analysis of the expression of receptors and enzymes related to the synthesis of neurotransmitters in striatum by PCR-RT revealed that HAL increased the expression of the dopaminergic receptors D1 and D2 and reduce an expression of the muscarinic receptors M1. Haloperidol decreased the expression of tyrosine hydroxylase (TH), a limiting step for the synthesis of dopamine. Taken together the results suggest that B vitamins prevented changes induced by HAL, presenting thus a promising role as a preventive approach against HAL-induced OD.
A Discinesia tardia (DT) é caracterizada por movimentos involuntários, principalmente na parte inferior da face, próximos da boca, com espasmos que podem ser leves ou severos. É uma alteração motora grave relacionada, mas não restrita à terapia antipsicótica. Tratamentos com antipsicóticos principalmente os da classe dos típicos, como o haloperidol (HAL) aumentam os riscos de DT. A fisiopatologia da DT é associada a um desequilíbrio em sistemas de neurotransmissão, dentre eles dopaminérgico e colinérgico, bem como com desequilíbrio oxidativo, principalmente em áreas cerebrais relacionadas ao controle do movimento, como o corpo estriado. As vitaminas (vit.) B, por sua vez, apresentam efeitos antioxidantes sendo cofatores para enzimas relacionadas à síntese de neurotransmissores. Neste contexto, o presente trabalho teve como objetivo determinar os efeitos preventivos das vit. B1, B6, B12 ou Complexo B na discinesia orofacial (DO) induzida por HAL em ratos. Foram utilizados ratos Wistar machos tratados por via intraperitoneal com HAL (1 mg/kg, i.p.) por 21 dias ou concomitantemente com HAL e as vit. B1 (60 mg/kg), B6 (60 mg/kg) ou B12 (0,6 mg/kg) por via subcutânea, sozinhas ou em associação (complexo B). O complexo B consistiu na mistura das 3 vitaminas em iguais proporções. Um grupo de animais foi administrado clozapina (25 mg/kg), um antipsicótico atípico não relacionado ao desenvolvimento de DO. Os testes comportamentais foram realizados após 30 minutos no 1º, 7º e 21º dias de administração das fármacos e consistiram na determinação da atividade locomotora, catalepsia e movimentos de mastigação no vazio. No 21° dia os animais foram sacrificados e retiradas áreas cerebrais para as análises neuroquímicas e de expressão para tirosina hidroxilase (TH), receptores dopaminérgicos D1 e D2 e receptor muscarínico M1. Os resultados mostraram que o HAL aumentou o tempo de catalepsia no dia 7 e causou DO no dia 21. A administração das vit. B (B1: B6: B12) sozinhas ou em associação, juntamente com HAL, preveniu o desenvolvimento de DO e em menor extensão da catalepsia. O efeito preventivo das vit. B foi acompanhado por restauração dos níveis de glutationa reduzida (GSH) e peroxidação lipídica. Além dos efeitos antioxidantes, as vit. B aumentaram a atividade da enzima acetilcolinesterase (AChE) em todas as áreas cerebrais estudadas, com o incremento máximo de atividade observada no hipocampo de animais co-tratados com vit. B12 e coquetel de vit. B. A clozapina não induziu DO e aumentou a atividade AChE semelhante para os grupos co-administrados com vit. B e HAL. A análise da expressão de receptores e enzimas relacionadas à síntese de neurotransmissores no corpo estriado por PCR-RT revelou que o HAL foi capaz de aumentar a expressão de receptores dopaminérgicos D1 e D2 e reduzir a expressão dos receptores muscarínicos M1. A expressão da tirosina hidroxilase (TH), passo limitante para a síntese de dopamina, se apresentou reduzida pelo HAL. Os dados sugerem que as vitamina do complexo B são capazes de prevenir as alterações induzidas pelo HAL apresentando, portanto, um papel promissor na prevenção de DO associada ao uso desta fármaco.
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Tang, Jing Jing. "Intérêt du profil chromatographique des acides organiques urinaires pour le diagnostic de carences en vitamines du groupe B (B1, B2, B8, B12)." Nutrition humaine, 1993. http://www.theses.fr/1993NAN10258.
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Murray, Louise M. "Comparative study of vitamin B12 and holotranscobalamin or active B12 as a marker for vitamin B12 deficiency at Dr George Mukhari Hospital." Thesis, University of Limpopo (Medunsa Campus), 2012. http://hdl.handle.net/10386/774.
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Thesis (M Med (Chemical Pathology)) -- University of Limpopo, 2012.Abstract Aim: This study was undertaken to compare the diagnostic sensitivity and specificity of total vitamin B 12 analyses to active B 12 (holoTC) analyses in a population of patients attending the Dr George Mukhari Hospital in Pretoria. Methods: Routine serum folate, full blood count (FBC), thyroid function test, homocysteine, serum total vitamin B 12 and active B 12 analyses were performed on 30 samples. Results: Serum folate was determined in all patients and 96% of the patients had a normal folate value. When looking at the FBC results it is important to note that three times as many males as females presented with anemia (36% versus 16%). Thyroid function tests were normal in 90% of patients. When the total vitamin B 12 test was preformed only 10% of patients tested positive for vitamin B 12 deficiency, in contrast to the active B12 analyses where 16% of patients tested positive for vitamin B12 deficiency. Both tests had a diagnostic sensitivity of 50%. The diagnostic specificity for total vitamin B12 was 93% in comparison with the 86% obtained by the active B12 analyses; when homocysteine was used as the true marker for vitamin B12 deficiency. Conclusion: Diagnostic sensitivity was the same and the total vitamin B12 test's specificity was better in comparison to the active B 12 analyses. Thus the active B 12 assay cannot be recommended for routine use, since it has no benefit.
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Divya, Jagasia, and Ferrando Vanesa Zanzi. "Tempeh: a tempting potential vitamin B12 treat : An exploration of legumes and vitamin B12." Thesis, Uppsala universitet, Institutionen för kostvetenskap, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-255419.
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Background: Legumes are beneficial for the environment, nutritious and coupled with various health benefits. However, they lack the essential vitamin B12 and a vitamin B12 deficiency can lead to hazardous health problems. Tempeh is a fermented legume product that has the potential of carrying vitamin B12. Aim: The aim of this thesis is to investigate consumers' awareness of vitamin B12 and explore the indications for the possibility to introduce tempeh - a fermented legume product. Method: A quantitative survey was carried out within four different areas of Stockholm using a clustering sample technique with 195 participants who were recruited outside supermarkets through convenience sampling. Results: The majority of the subjects had moderate consumption of legumes and was open to trying tempeh even though they had never heard about it. While their knowledge of vitamin B12 was limited, the biggest risk groups, vegans and the elderly, were aware that they were a risk group but only a minority of them knew the correct vitamin B12 food sources. Conclusion: The participants in this study had little knowledge about vitamin B12 food sources, deficiencies or risk groups. Since their legume consumption was regular and they were positive towards trying tempeh even though they had never heard about tempeh before, there is potential for it in the market. However, more studies are needed to research the bioavailability of vitamin B12 in tempeh even though new research gives hope that it can be a possibility.
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Ferreira, Marianna Boia. "Avaliação do papel da proteína TCTP em melanoma murino (B16-F1 e B16-F10)." reponame:Repositório Institucional da UFPR, 2014. http://hdl.handle.net/1884/49141.
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Orientadora : Profª. Drª. Andrea Senff RibeiroCoorientador : Prof. Dr. Silvio Sanches Veiga
Dissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências Biológicas, Programa de Pós-Graduação em Biologia Celular e Molecular. Defesa: Curitiba, 27/02/2017
Inclui referências : f. 73-83
Resumo: O tumor do tipo melanoma da pele apresenta baixa incidência contudo, sua letalidade é extremamente elevada. As linhagens B16 constituem um modelo de melanoma murino muito útil na oncologia experimental. A linhagem B16F10 apresenta alta capacidade de invasão e metastização enquanto que a linhagem B16-F1 apresenta menor motilidade in vitro e, portanto, baixo potencial metastático. A TCTP (Translationally Controlled Tumor Protein) é expressa em diversos organismos e tecidos, o que aponta um papel biológico fundamental. Diferentes estudos já estabeleceram seu envolvimento na regulação do ciclo e proliferação celular, bem como na malignidade e como fator protetor contra estresse e apoptose. Dessa forma, o objetivo desse trabalho foi avaliar o papel da TCTP em melanoma murino (B16F1 e B16F10). O perfil proteico bidimensional apresentado pelas linhagens foi diferente: a linhagem B16-F10 apresentou 201 spots e a linhagem B16-F1 126 spots. Essa diferença pode estar relacionada à complexidade celular da B16-F10, mais maligna e metastática. Em ambos os extratos foi identificada uma proteína com mobilidade eletroforética de 20 kDa e pI de 4,8 (valores esperados para TCTP). Além disso, a TCTP foi imunodetectada por western blotting. A linhagem B16- F1 apresentou um menor sinal de detecção quando comparada à B16-F10., Essa diferença poderia estar associada a uma maior expressão de TCTP em células tumorais mais metastáticas e invasivas e, consequentemente, a B16F10 apresentaria níveis superiores de TCTP. Esta hipótese foi confirmada por PCR em tempo real: B16-F10 apresentou níveis de RNAm para TCTP superiores aos encontrados para B16-F1. Esses dados corroboram com os resultados do western blotting e com dados da literatura que relacionam a TCTP à linhagens malignas, devido ao seu papel anti-apoptótico e seu antagonismo com a p53. A fim de avaliar o papel biológico da TCTP no melanoma, esta foi silenciada na linhagem B16-F10, utilizando a técnica de RNAi. O silenciamento diminuiu os níveis de TCTP em 50 a 70% quando utilizado 50 nM e 60 a 80% quando utilizado 100 nM do duplex após 24, 48 e 72 horas de transfecção. As linhagens transfectadas com RNAi para TCTP apresentaram menor proliferação, menor migração e maior adesão celular às moléculas da matriz extracelular quando comparadas às linhagens transfectadas com o controle negativo. Porém, não houve qualquer alteração significativa da viabilidade celular. O aumento da proliferação celular e do potencial migratório são dois eventos muito importantes para a tumorigênese, e estão intimamente relacionados à malignidade. Portanto, o silenciamento foi capaz de regredir o fenótipo de malignidade da linhagem B16-F10, deixando esse mais próximo da B16-F1. Dessa forma, nosso estudo caracterizou os perfis celulares das duas linhagens e demonstrou uma diferença no número de proteínas e parceiros moleculares entre ambas linhagens. Além disso, nossos dados sugerem que o silenciamento da TCTP tornou a linhagem B16-F10 menos metastática e maligna, com um fenótipo mais próximo ao de uma célula normal. Mais estudos são necessários com o intuito de identificar possíveis parceiros e melhor entender o papel dessa proteína multifuncional no melanoma murino. Palavras-chave: TCTP, melanoma, B16-10, B16-F1, câncer
Abstract: Skin melanoma tumor displays low incidence, however, its lethality is extremely high. B16 cell lines typify a murine melanoma model very useful on the experimental oncology field. B16-F10 cell line exhibits high invasion and metastization capacities while B16-F1 cell line depicts lower in vitro motility and, therefore, low metastasis potential. TCTP (translationally controlled tumor protein) is expressed in several organisms and tissues, which suggests a fundamental biological role. Different studies have already settled its participation in cell cycle regulation and cell proliferation, as well as in malignancy and as a protective factor against stress and apoptosis. Thus, this study aimed to assess the TCTP role in in murine melanoma (B16-F1 and B16- F10). Two-dimensional electrophoresis profiles of proteins from the two cell lines were different: B16-F10 cells presented 201 electrophoresis spots while B16-F1 originated 126 spots. This difference may be related to the B16-F10 cell complexity, since this cell line is more malignant and metastatic. In both cell extracts was identified a protein with electrophoretic mobility about 20 kDa and deduced pI of 4.8 (expected parameters for TCTP). Furthermore, TCTP was immunodetected by western blotting analysis. B16-F1 cells produced low detection signals when compared to the B16-F10 cells. This difference may be associated to the higher TCTP expression in more metastatic and invasive tumoral cells and, consequently, B16-F10 would present higher TCTP levels. This hypothesis was confirmed by Real-Time PCR, since B16-F10 revealed RNAm levels for TCTP higher than the B16-F1. These data corroborate with western blotting results and the specific literature, which connect TCTP and malignant cell lines due to the anti-apoptotic function and its p53 antagonism. In order to evaluate the biological role of TCTP in melanoma, it was performed the TCTP silencing in B16-F10 cell line by using RNA interference (RNAi) method. The gene silencing reduced TCTP levels in 50% to 70% when used 50 nM and 60% to 80% when used 100 nm of the duplex after 24, 48 and 72 hours of transfection. The transfected cell lines with RNAi for TCTP presented lower proliferation, lower migration and higher cell adhesion to extracellular matrix molecules when compared to the cell lines transfected with negative control. However, there was no significant change in cell viability. Increasing cell proliferation and migration potential are two events very important for the tumorigenesis process and they are closely related to the malignancy. Therefore, gene silencing was able to recede the malignant phenotype of B16- F10 cell line, resulting in a similar aspect to the B16-F1 cells. Thus, this study characterized the profile of two cell lines and it demonstrated differences in protein number and molecular partners between these two cell lines. Moreover, the generated data suggest that TCTP gene silencing became B16-F10 cells less metastatic and malignant, resembling the normal cell phenotype. Further studies are necessary in order to identify possible partners and to better understand the TCTP role in the murine melanoma. Key-words: TCTP, melanoma, B16-10, B16-F1, cancer.
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Pozzuto, Tanja [Verfasser]. "Untersuchung des Rezeptor-vermittelten Aufnahmemechanismus von Parvovirus B19 bei der endothelialen Parvovirus B19-Infektion und Adenovirus-induzierte Reaktivierung von Parvovirus B19 in Endothelzellen / Tanja Pozzuto." Berlin : Freie Universität Berlin, 2012. http://d-nb.info/1030291640/34.
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Pozzuto, Tanja Donatina [Verfasser]. "Untersuchung des Rezeptor-vermittelten Aufnahmemechanismus von Parvovirus B19 bei der endothelialen Parvovirus B19-Infektion und Adenovirus-induzierte Reaktivierung von Parvovirus B19 in Endothelzellen / Tanja Pozzuto." Berlin : Freie Universität Berlin, 2012. http://nbn-resolving.de/urn:nbn:de:kobv:188-fudissthesis000000039993-6.
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Zant, Ayman [Verfasser], and Rima [Akademischer Betreuer] Obeid. "Auswirkung einer mit Vitamin B12 angereicherten Zahncreme auf Plasma-Vitamin-B12 / Ayman Zant ; Betreuer: Rima Obeid." Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2019. http://d-nb.info/1213294606/34.
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Munter, Emily J. "Seasonal prescribed fire effects on cheatgrass and native mixed grass prairie vegetation /." Chadron, Neb. : Chadron State College, 2008. http://www.nlc.state.ne.us/epubs/G1000/B134-2008.pdf.
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Thesis submitted to the graduate faculty of Chadron State College in partial fulfillment of the requirements for the degree of Master of Arts in Education."October, 2008". Includes bibliographical references (p. 59-64). Also available in PDF via the World Wide Web.
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Kerr, Jonathan Richard. "The pathogenesis of parvovirus B19 infection." Thesis, Queen's University Belfast, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.282038.
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Anderson, R. J. "B1̲2̲ models : Synthesis and reactions." Thesis, University of Newcastle Upon Tyne, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.383946.
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Page, Cyril. "Erythrovirus B19 et maladie de Basedow." Amiens, 2012. http://www.theses.fr/2012AMIED003.
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Objectifs du travail : il s’agissait de mettre en évidence la présence d’EVB19 dans le sérum et le tissu thyroïdien de patients opérés de thyroïdectomie totale pour maladie de Basedow (cas) ou de goitre multi-hétéro-nodulaire bénin sans auto-immunité thyroïdienne associée (témoins). Matériel et méthode : Il s’agissait d’une étude rétrospective avec recrutement prospectif de patients opérés de thyroïdectomie totale effectuée sur une période de 5 ans au CHU d’Amiens, France. Tous les patients ont bénéficié en préopératoire d’une sérologie anti EVB19 (recherche d’IgG et d’IgM anti-VP1 et anti-VP2 ), d’une qPCR sérique avec quantification de la charge virale d’EVB19 (Kit commercial Qiagen®) et une étude immuno-histochimique (anticorps polyclonal de lapin anti VP2 , Dako®) sur lames de paraffine des pièces de thyroïdectomie à la recherche de l’expression de la protéine virale VP2 Résultats : 64 patients (20 Basedow, 44 témoins) ont été inclus dans l’étude. Aucune infection aiguë ou chronique à EVB19 n’ont été mises en évidence (négativité des IgM et charge virale nulle pour tous les patients). La séropositivité pour l’EVB19 était plus fréquente dans le groupe témoins que dans le groupe Basedow (88% vs 45%, p<0. 0001). L’immuno-histochimie était positive (mise en évidence d’une fixation cytoplasmique au niveau des thyréocytes) dans 10% des cas de maladie de Basedow et dans 27,27 % des GMHN, sans différence significative entre ces deux groupes. Conclusion : L’EVB19 peut être mis en évidence dans les thyréocytes de patients atteints de maladie de Basedow ou de GMHN. Aucune association ou de relation de cause à effet n’ont pu être mise en évidence. D’autres études sont nécessaires pour déterminer si l’EVB19 joue un rôle en pathologie thyroïdienne.
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CERCLE, DOMINIQUE. "Infection a parvovirus b19 et grossesse." Nantes, 1994. http://www.theses.fr/1994NANT016M.
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Martens, Jan-Henning. "Gezielte Entwicklung von Bacillus megaterium für biotechnologische Anwendungen." [S.l. : s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=96717869X.
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Müller, Britta. "Untersuchung der anaeroben Spaltung von Ethern am Beispiel des 2-Phenoxyethanol-Abbaus durch Acetobacterium Stamm LuPhet 1." [S.l. : s.n.], 2006. http://nbn-resolving.de/urn:nbn:de:bsz:352-opus-67421.
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Breen, Alexis Julie. "Effects of the social and physical environment on avian nest construction." Thesis, University of St Andrews, 2019. http://hdl.handle.net/10023/17102.
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Singh, Deeba. "Phosphorylation sites on specific neuronal proteins can control the mode of synaptic vesicle exocytosis and thereby regulate synaptic transmission." Thesis, University of Central Lancashire, 2017. http://clok.uclan.ac.uk/23988/.
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Synaptic vesicles (SVs) can exocytose via Full fusion (FF) or by Kiss-and-Run (KR) mechanisms. In this thesis, synaptosomes prepared from adult rat cerebrocortex demonstrated that these modes can be switched by regulating the intracellular calcium levels and/or protein phosphorylation reactions. The stimuli employed were: 30 mM K+ (HK), 1 mM 4-aminopyridine (4AP) and 5 mM ionomycin (ION) together with 5 mM Ca2+. In this model employed, myosin-II and dynamins can regulate the closure of the fusion pore of the readily releasable pool (RRP) of SVs during KR but are independent of each other’s actions. In biochemical assays, synaptosomes were maximally labelled with FM2-10 dye such that both the RRP and the RP were loaded and such terminals were subsequently evoked to release the dye and this was compared to the endogenous release of glutamate (GLU). Results show that the rise in [Ca2+]i at the active zone produced by HK5C activates PKC isoforms, which in turn cause phosphorylation of myosin-II and dynamins. It is hypothesised that dynamins are active at relatively lower increases in [Ca2+]i that do not activate PKCs whereas myosin-II is active at relatively higher increases in [Ca2+]i that activate certain PKCs. Such activation of PKC stimulates myosin-II -but inhibits the action of dynamins – and it is this active protein that can close the fusion pore. ION5C, however, activates dynamin(s) but not myosin-II, and under such conditions dynamin can close the fusion pore. This dynamin-dependent KR mode is independent of clathrin because this is not perturbed by the blockade of clathrin action using the drug, pitstop2TM and the HK5C evoked myosin-II-dependent KR is independent of both clathrin and dynamin. Therefore, the KR mechanism described, herein, is distinct from ultra-fast endocytosis that has both a dynamin and clathrin dependence. Pre-treatment of synaptosomes with DYN and/or pitstop2TM prior to the initial pre-stimulation with HK5C inhibits all dynamin and clathrin dependent processes so that SVs that recycle after the HK5C pre-stimulation would be perturbed if they had such a requirement. Indeed, following this treatment some SVs were not released by ION5C, although, the 4AP5C evoked GLU release is not affected and it would appear that the 4AP5C sensitive pool (the RRP) can still release following blockade of dynamin and clathrin. This demonstrates that the RRP underwent KR during the first pre-stimulus (actually via a myosin-II- dependent process) and was available to release again during the second round, and again this cannot be via ultra-fast endocytosis. The role of cAMP and PKA pathways in regulating the modes was investigated. Adenylate cyclase activation by forksolin inhibits the release of the RP but switches all the RRP vesicles to KR when evoked by 4AP5C. Adenylate cyclase inhibition by 9-Cyclopentyl-Adenine (9-Cp-Ade) has no effect on GLU release or exocytotic mode. Forskolin’s action on the RP is due to a specific increase in cAMP, because pre-treatment of synaptosomes with 9-Cp-Ade before forskolin prevents the forkskolin action. The PKA activator, Sp-5,7-dichloro-cBIMPs (cBIMPS) does not affect evoked GLU release although it does switch some of the RP to a KR mode whereas inhibiting PKA with KT 5720 has not effect on GLU release but induces the RRP to undergo FF. Clearly, forskolin’s action on both the RP and the RRP SVs is distinct from PKA activation and it may work through activating the exchange protein directly activated by cAMP (EPAC). Previous experiments have showed that inhibition of protein phosphatase 2A (PP2A) by okadaic acid (OA) switches the RRP to FF for all stimuli, but OA pre-treatment before forskolin failed to prevent 4AP5C switching some SVs in the RRP from FF to KR. This suggests that an adenylate cyclase pathway can override the OA-sensitive pathway. The Seahorse extracellular flux analyser was used to measure various mitochondrial respiration parameters (basal, ATP production, spare capacity, maximum respiration, proton leakage and non-mitochondrial respiration). Employing 0.3 and 3 mM phenyl arsine oxide appears to perturb the spare respiratory capacity, whilst 0.1 mM did not. This indicated that we were previously using too high a concentration of this drug to study modes of exocytosis. Such a result led to the testing of the drugs employed in this study on exocytosis to check that they did no produce a non-specific effect on the bioenergetics of the synaptosomes: 9-Cp-Ade, Blebb, Go 6983, cBIMPs, forskolin or OA did not change the mitochondrial respiratory parameters indicating that any exocytotic effects shown were specific. The specific phosphorylation of Ser-778, Ser-774 and Ser-795 on dynamin 1 was investigated using well characterized commercial antibodies and western blotting. It was concluded that the phosphorylation of Ser-774 and Ser-778 showed no correlation with dynamin’s activity towards regulating closure of the fusion pore although these sites may well correlate with clathrin dependent endocytosis and bulk endocytosis. However, the phosphorylation of Ser-795 on dynamin may play an important role in the inhibition of dynamin’s activity towards closing the fusion pore during KR. Phosphorylation on Ser-795 may be under the regulation of PKC as demonstrated using a PKC activator, phorbol myristate acetate, and an inhibitor, Go 6983. Therefore, endogenous PKC activation may phosphorylate this site when a very high Δ[Ca2+]i is achieved at the active zone. It was difficult to obtain a conclusion as to which PKC isoform could regulate the mode of SV exocytosis by phosphorylation of Ser-795 on dynamin due to the low phosphorylation levels obtained whilst employing Go 6983 and Go 6976.
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Enyindah-Asonye, Gospel. "PATHOPHYSIOLOGICAL ROLE OF CD6 AND ITS NEW LIGAND IN DISEASES." Case Western Reserve University School of Graduate Studies / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=case1491389112552353.
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Heilmann, Romy Monika, Niels Grützner, Christina M. Iazbik, Rosana Lopes, Seth C. Bridges, Jan S. Suchodolski, Guilermo C. Couto, and Jörg M. Steiner. "Hyperhomocysteinemia in greyhounds and its association with hypofolatemia and other clinicopathologic variables." Universitätsbibliothek Leipzig, 2016. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-213902.
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Background: Folate and cobalamin are essential cofactors for homocysteine (HCY) metabolism. Hyperhomocysteinemia, a multifactorial condition, may reflect B vitamin deficiency and is associated with increased risk of cardiovascular disease, thrombosis, and neurodegenerative and chronic gastrointestinal diseases in humans. Hyperhomocysteinemia has been reported in Greyhounds with suspected chronic enteropathy. Objectives: To evaluate the frequencies of and the association between hypofolatemia and hyperhomocysteinemia in Greyhounds. Animals: Data and serum samples from 559 Greyhounds. Methods: Nested case-control study. The frequency of hypofolatemia in Greyhounds was determined by a laboratory database search. The relationship between hyperhomocysteinemia (measured by gas chromatography-mass spectrometry) and hypocobalaminemia and hypofolatemia was evaluated, and its frequency compared between healthy Greyhounds and Greyhounds with thrombosis or chronic diarrhea. Results: Hypofolatemia was identified in 172 of 423 (41%) Greyhounds and was more common in hypo- than in normocobalaminemic dogs (49% vs. 35%; P = .0064). Hyperhomocysteinemia was detected in 53 of 78 (68%) of Greyhounds, being more common in hypo- than in normofolatemic dogs (88% vs. 59%; P = .0175). All healthy Greyhounds, 21 of 30 (70%) of dogs with chronic diarrhea and 6 of 8 (75%) of those with thrombosis, were hyperhomocysteinemic. Serum HCY concentrations were inversely correlated with serum folate concentration (q = -0.28; P = .0386) and were positively associated with
serum albumin concentration (q = 0.66; P = .0022). Conclusions and Clinical Relevance: Hyperhomocysteinemia occurs frequently in the Greyhound population. Its association with hypofolatemia suggests decreased intracellular availability of B vitamins, but the functional implications warrant further investigation. Hyperhomocysteinemia in Greyhounds potentially may serve as a spontaneous canine model to further investigate hyperhomocysteinemia in humans.
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McGoldrick, Helen Margaret. "Cobalamin (vitamin B12) biosynthesis in rhodobacter capsulatus." Thesis, Queen Mary, University of London, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.415432.
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Jiang, Dong. "Model studies of coenzyme B12 dependent reactions." Thesis, University of Newcastle Upon Tyne, 2010. http://hdl.handle.net/10443/989.
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Coenzyme-B12 dependent glutamate mutase is a radical enzyme, which catalyses the isomerisation of (S)-glutamate to (2S,3S)-3-methylaspartate via enzyme-bound radical intermediates. This is the key step in the fermentation of glutamate to ammonia, carbon dioxide, acetate, butyrate and hydrogen by Clostridium tetanomorphum. It has been proposed that the mechanism of glutamate mutase involves removal of Hsi from glutamate to give a 4-glutamyl radical that undergoes fragmentation to acrylate and a glycine radical. Recombination of these species leads to the 3-methylene-aspartate radical and hence (2S,3S)-3-methylaspartate. Glutamate mutase has an active site containing three arginine residues that bind to the carboxylate groups of substrate, intermediates and product, the so-called ‘arginine claw’. The model compound containing two guanidinium groups, 2,3-bisguanidinomethyl- biphenyl dihydrochloride, has been synthesised in order to probe the function of this peculiar enzyme active site. NMR titration results showed that the receptor binds weakly to tetrabutylammonium glutarate in CD3OD. To identify possible intermediates for the glutamate mutase catalysed reaction, a precursor for the product-related radical 3-methyleneaspartate has been designed and its synthesis has been explored. Diol dehydratase from e.g. Klebsiella oxytoca is a radical enzyme that converts simple 1,2-diols into corresponding aldehydes and water. The enzyme requires adenosylcobalamin (coenzyme B12) as cofactor and a metal cation (e.g. K+). The mechanism of action of the dehydratase has previously been investigated by protein crystallography and ab initio molecular orbital calculations, aided by stereochemical and model studies. The 5'-deoxyadenosyl radical from homolysis of the coenzyme’s Co-C bond abstracts a specific H atom from C-1 of diol substrate giving a substrate radical that rearranges to a product radical by 1,2-shift of hydroxyl from C-2 to C-1. It has been proposed that the rearrangement mechanism involves the action of acidic and basic residues in the protein, with the involvement of a bridged intermediate. iv Dong Jiang, Newcastle University, PhD Thesis, 2010 Ethanolamine ammonia-lyase (EAL) from e.g. Clostridia sp. converts ethanolamine into acetaldehyde and ammonia by a similar pathway. Fluorine-substituted probes for coenzyme B12-dependent enzymatic reactions: 3,3,3- trifluoropropane-1,2-diol for diol dehydratase and 2-amino-3,3,3-trifluoropropanol for EAL, have been synthesised. 3,3,3-Trifluoropropane-1,2-diol is a substrate for glycerol dehydratase (ca. 4 % of the activity of propane-1,2-diol). This result is surprisingly in the context of the proposed mechanism for diol dehydratase, although ab initio molecular orbital calculations (collaboration with Dr D. M. Smith, Zagreb) have indicated that CF3 has a minimal effect on the stabilities of the proposed intermediates. A model study (performed in collaboration with Dr C. Chatgilialoglu, Bologna) showed that 1,1-difluoro-3-hydroxylpropanone was formed by continuous -irradiation of 3,3,3-trifluoropropane-1,2-diol. The expected 3,3,3-trifluoropropanal and 1,1,1-trifluoroacetone could not be determined from the 1H NMR analysis of the irradiation mixuture. Propanal and acetone were formed by the continuous - irradiation of propane-1,2-diol (analysis by GC and GC-MS, and by formation of the corresponding 2,4-dinitrophenylhydrazones). 2-Amino-3,3,3-trifluoropropanol was found to be devoid of any activity against EAL according to a coupled assay with alcohol dehydrogenase (collaboration with Dr G. H. Reed, University of Wisconsin-Madison). EPR study (collaboration with Dr K. Warncke, Emory University) has concluded that the CF3-substrate did not lead to the significant formation of a paramagnetic intermediate. This may be due to the CF3 group reducing the basicity of the amino group and the acidity of the alcohol group and so that there is a significant diminished interaction with the active site in EAL. Or this may be caused by the significant steric effect introduced by the trifluoromethyl group (CF3 group is between two and three times larger than CH3).
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Labbé, Michelle. "Les infections a parvovirus b19 chez l'enfant." Nantes, 1990. http://www.theses.fr/1990NANT161M.
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Shinohara, Elvira Maria Guerra. "Prevalência de anemia em gestantes de primeira consulta em centros de saúde do estado no Subdistrito de Paz do Butantã, Município de São Paulo." Universidade de São Paulo, 1989. http://www.teses.usp.br/teses/disponiveis/9/9136/tde-27032008-142216/.
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Foram estudadas 363 gestantes de primeira consulta, que não faziam uso de medicamentos que continham ferro, ácido fólico, vitamina B12 ou associação destes, na ocasião da coleta do material, em Centros de Saúde do Estado, no Subdistrito de Paz do Butantã, município de São Paulo. A prevalência de anemia (concentração de hemoglobina inferior a 11,6 g/dl) foi de 12,4%. As médias das concentrações de hemoglobina e as prevalências de anemia, segundo o trimestre de gestação, foram respectivamente: 13,47 g/dl e 3,57% no primeiro, 12,47 g/dl e 20,86% no segundo e 12,25 g/dl e 32,14% no terceiro trimestre. Não encontramos diferença. estatisticamente significativa entre as médias das concentrações de hemoglobina e entre as prevalências de anemia nas gestantes primigestas e multigestas. O mesmo aconteceu com as médias e as prevalências das gestantes multigestas com intervalo do último parto até dois anos e maior que dois anos. Na amostra estudada, encontramos maior prevalência de anemia naquelas gestantes que pertenciam às famílias que tinham renda per capita até 0,5 SMPC (salário mínimo per capita). As prevalências de verminose e de ancilostomídeos nas 300 gestantes foram respectivamente: 64,7% e 14,0%. Nas gestantes anêmicas foram respectivamente: 73,7% e 7,9%. Nas gestantes anêmicas, a prevalência de deficiência de ferro foi de 42,2% (concentração de ferro sérico <50 µg/dl) ou 46,7% (saturação da transferrina <15% ou 40,0% (concentração de ferro sérico <50 µg/dl e saturação de transferrina <15%). A prevalência de deficiência de ácido fólico foi 44,4%. A prevalência de deficiência de ferro e ácido fólico foi de 17,8%. Não encontramos deficiência de vitamina B
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Sillaots, Susan L. (Susan Linda). "Heterogeneity in cblG : differential binding of vitamin B12 to methionine synthase." Thesis, McGill University, 1991. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=60091.
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Fibroblasts from patients with functional methionine synthase deficiency can be divided into 2 complementation classes, cblE and cblG. Both have low levels of intracellular methylcobalamin. Both groups also demonstrate low levels of incorporation of label from 5-methyltetrahydrofolate into macromolecules. Under standard reducing conditions, methionine synthase specific activity is normal in cblE fibroblast extracts, but is low in cblG fibroblast extracts. Seven cblE and seven out of ten cblG cell lines demonstrate levels of accumulation of ($ sp{57}$Co) CN-Cbl in fibroblasts comparable to that of control cells. They exhibit similar proportions of label associated with the two intracellular cobalamin binders, methylmalonyl-CoA mutase and methionine synthase. The remaining three cblG cell lines exhibit a lower level of cobalamin accumulation, and demonstrate a lack of cobalamin association with the enzyme methionine synthase. The specific activity of methionine synthase is almost undetectable in the three cblG cell lines that showed no such association. These results demonstrate heterogeneity within the cblG group and suggest that the defect in cblG affects the methionine synthase apoenzyme.
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Vassiliadis, Anthony. "Electron microscopic radioautographic localization of [57Co]Cobalamin in cb1F and control cells." Thesis, McGill University, 1989. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=55659.
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Law, John N. E. "Rethinking federalism." Thesis, University of Oxford, 2010. http://ora.ox.ac.uk/objects/uuid:a3357b7c-7f08-4074-b914-6f06ce6ce01d.
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This thesis is motivated by uncertainty in the academic literature surrounding the meaning of federalism and the appropriate usage of the concept to describe political systems. In particular, its use in characterising systems of regional integration which have moved beyond a strictly inter-governmental character, but not yet reached Statehood, is today highly contested, as in the case of the European Union. The established consensus that this entity constitutes a wholly novel ‘sui generis’ form, neither federal nor confederal in character, has been tempered in recent years by a growing willingness among scholars to deploy the lens of comparative federalism to analyse the polity. However, the precise relevance of the concept in this new context remains unsettled. Can political science achieve any more definite understanding that removes such doubt? I consider this question through the perspective of the history of ideas, by examining the evolution of federalism from inception to the present day. I argue that the history of the federal idea in the United States reveals that the heart of the problem lies in confusion over the nature of sovereignty. Ever since Philadelphia federalism has been thought to mean ‘a division of sovereignty’. However, the subsequent Civil War did appear to demonstrate that the notion of sovereignty shared between two levels of government was a false construction: either the whole or the parts could be sovereign, but not both simultaneously. This point, it seems - the indivisibility of sovereignty - was not fully taken on board afterwards in the United States and elsewhere. The thesis seeks to put this right and to systematically relate the evolving concept of federalism with the evolving and contested nature of sovereignty. On this ground, I suggest that we clarify the definition of federalism as ‘a division of the powers flowing from sovereignty’. This in turn yields two specific varieties of ‘compound polity’ where before only one was known: the single State and multi-State federal forms. The latter has to date been an unobserved species, which, it would seem, the fact of the EU’s existence now forces us to recognize.
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Levine, Shari. "On cleavability." Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:feb28947-c21a-4149-b1d4-e21548da8af5.
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This thesis concerns cleavability. A space X is said to be cleavable over a space Y along a set A subset of X if there exists a continuous function f from X to Y such that f(A) cap f(X setminus A) = emptyset. A space X is cleavable over a space Y if it is cleavable over Y along all subsets A of X. In this thesis we prove three results regarding cleavability. First we discover the conditions under which cleavability of an infinite compactum X over a first-countable scattered linearly ordered topological space (LOTS) Y implies embeddability of X into Y. In particular, we provide a class of counter-examples in which cleavability does not imply embeddability, and show that if X is an infinite compactum cleavable over ω1, the first uncountable ordinal, then X is embeddable into ω1. We secondly show that if X is an infinite compactum cleavable over any ordinal, then X must be homeomorphic to an ordinal. X must also therefore be a LOTS. This answers two fundamental questions in the area of cleavability. We also leave it as an open question whether cleavability of an infinite compactum X over an uncountable ordinal λ implies X is embeddable into λ. Lastly, we show that if X is an infinite compactum cleavable over a separable LOTS Y such that for some continuous function f from X to Y, the set of points on which f is not injective is scattered, then X is a LOTS. In addition to providing these three results, we introduce a new area of research developed from questions within cleavability. This area of research is called almost-injectivity. Given a compact T2 space X and a LOTS Y, we say a continuous function f from X to Y is almost-injective if the set of points on which f is not injective has countable cardinality. In this thesis, we state some questions concerning almost-injectivity, and show that if lambda is an ordinal, X is a T2 compactum, and f is an almost-injective function from X to lambda, then X must be a LOTS.
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Hancock, Laura M. "Anion-templated synthesis of functional interlocked architectures." Thesis, University of Oxford, 2011. http://ora.ox.ac.uk/objects/uuid:d4f141f6-fd44-49cc-b14b-0dec22679c75.
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This thesis explores the use of anions in the design and construction of interlocked architectures for applications in anion recognition and sensing, and to function as molecular machines upon a given stimulus. Chapter One introduces the field of anionic supramolecular chemistry focusing on host-guest chemistry and directed self-assembly. A review of the recognition and sensing of anionic guest species is given before strategies for the construction of interlocked architectures are discussed, and the potential functions of these structures considered. Chapter Two details the development of a novel anion-templation route for the synthesis of macrocycles and rotaxanes. The versatility of this route in constructing new [2]rotaxanes is explored by varying several features of the macrocyclic component, with emphasis on creating the most powerful anion complexant. Proton NMR spectroscopy is used to probe the anion binding properties of the rotaxanes, and X-ray crystallography and MD simulations are used to rationalize anion binding trends. The possibility of synthesizing catenanes for anion recognition via this new synthetic route is also investigated. Chapter Three investigates the appendage of transition metal complexes to rotaxanes to create interlocked host architectures capable of sensing anions via luminescence spectroscopy. The incorporation of rhenium(I) and ruthenium(II) polypyridyl complexes into the macrocyclic and axle component of [2]rotaxanes are described, before the anion binding studies of these structures using ¹H NMR and luminescence spectroscopy are reported. Chapter Four describes the strategic synthesis of [2]rotaxanes designed to undergo molecular motion upon a given stimulus. Initially, the possibility of exploiting anions to stimulate the macrocyclic component of the [2]rotaxanes to translocate to a second station on the axle is investigated. The use of pyridine N-oxide as an integrated template for rotaxane formation is reported before the ability of these rotaxanes to undergo anion and pH driven molecular motion is explored. This chapter concludes with the construction of a calix[4]diquinone N-oxide containing [2]rotaxane capable of undergoing sodium- and barium-induced molecular pirouetting. Chapter Five provides synthetic procedures and characterisation details for compounds listed in this thesis. Chapter Six reports supplementary experimental information including titration protocols, X-ray crystal structures and MD simulations.
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Kelly, Simon. "Théodore Rousseau (1812-67), his patrons and his public." Thesis, University of Oxford, 1996. http://ora.ox.ac.uk/objects/uuid:fa6339c0-2c5d-4d84-b514-ab5ad003f4a1.
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This thesis is a case study of the relationship between a nineteenth-century French landscape painter, Théodore Rousseau, and his patrons and public. My aim is to reconstruct the context in which Rousseau's work was created, thereby inferring what the artist intended for his painting and how his collectors and public approached the style of his work. The thesis examines the nature of the dynamic between Rousseau and his consumers and the extent to which the artist's style may, or may not, be affected by the taste of his audience. In Part I, I examine Rousseau's involvement with the members of his circle including those who supported him during his years of absence from the Salon, the critic, Théophile Thoré, the industrialist, Frédéric Hartmannn and the civil servant, Alfred Sensier. This provides a framework for discussion of a number of ideas which preoccupied both the artist and his patrons including the level of finish in his work, the importance of pantheism, responses to commercial deforestation and the continuing resonances of ancient Greek culture. In Part II, I look at the problem of Rousseau's response to the expansion of the public sphere for art in the nineteenth-century. I approach this by locating Rousseau within the institutional structures of the art world which acted as intermediary between the painter and a wider public. These include the public exhibition, the rôle of the reproduction in the dissemination of his imagery, the importance of one-man public auctions and the position of the dealer as an outlet for the sale of his work. In reconstructing the dynamic between Rousseau and his patrons and public, I have relied above all on primary sources. These have included the often unpublished correspondence of the artist and his collectors, contemporary Salon criticism and sale catalogues, auctioneers' records and the stock-books of the Durand-Ruel firm of dealers, as well as a close formal analysis of Rousseau's paintings themselves.
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Bechev, Dimitar. "Constructing South East Europe : the politics of Balkan regional cooperation, 1995-2003." Thesis, University of Oxford, 2005. http://ora.ox.ac.uk/objects/uuid:b2c66c28-2d24-4e09-b184-5dd1155910ee.
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In the post-Cold War era, the Balkans came to exemplify the power of resurgent nationalisms freed from the straitjacket of bipolar stability. The break-up of the Yugoslav federation suggested that exclusivist ethno-national identities trumped the logic of political and economic integration. Yet, by the early 2000s, regional cooperation made significant inroads into South East Europe. This study addresses the puzzle of why the Balkan states have engaged in a number of multilateral schemes in fields such as military security, trade, infrastructure development, energy, despite the region's divisive historical legacies and political instability. The thesis explores the impact of three factors: regional interdependence denoting the socio-economic and political linkages which contribute to the convergence of Balkan states' material interests, external push referring to the policies for fostering regional cooperation adopted by key actors such as the EU, US, and NATO, and identity politics: the discourses on the borders, cultural make-up and history of a Balkan regional entity as well as the latter's relationship with constructs like Europe and the West. The thesis argues that external projection of power, rather than regional interdependence, accounted for the development and growth of Balkan regionalism. However, the push from outside was legitimised by Balkan collective identity built upon myths of belonging to and exclusion from 'civilised Europe'. Regionalism was not solely a reflection of the supply and demand for integrative frameworks, but amounted to a symbolic strategy for transforming the volatile Balkans into South East Europe by the adoption of the institutional norms and practices of international clubs such as the EU and NATO. The case of regional cooperation in South East Europe contributes to the debates about the politics of interest and the politics of identity in the field of International Relations, and raises questions about the nature of power in contemporary Europe and the international society.
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Nicholls, Matthew. "Roman public libraries." Thesis, University of Oxford, 2005. http://ora.ox.ac.uk/objects/uuid:b13e1d31-e076-4923-b147-5074d7f85770.
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This thesis aims to investigate the development and functions of public libraries in Rome and the Roman world. After a preface with maps of libraries in Rome, Section I discusses the precursors for public library provision in the private book collections of Republican Rome, and their transfer into the public domain with the first public libraries of Asinius Pollio and Augustus. Section II contains three 'case studies' of public libraries' different roles. The Augustan library programme is used in Ch.II.l to examine the role of imperial public libraries in literary life and the connections between Rome's libraries and those of Alexandria. Chapter II.2 concentrates on the libraries of Trajan's Forum to explore the intersection of imperial public libraries and monumental public architecture. This chapter responds to an important recent article by arguing for the continued identification of the Forum's libraries with twin brick buildings at its northern end, and suggests a series of correspondences between these libraries and its other monumental components. The conclusions of this chapter are important when considering the public libraries of the wider empire, several of which seem to have been inspired by the Trajanic libraries. Chapter II.3 considers imperial public libraries and leisure by looking at the evidence for libraries within bath-house complexes, concluding that their presence there is consistent with the archaeological and epigraphic evidence and fits in well with what we know of the intellectual and cultural life of these structures. Section III examines various aspects of the practical function of Roman public libraries: their contents (books and archives), division into Latin and Greek sections, provisions for shelving and cataloguing, staff, usership, architectural form, decoration, and housing of works of art. The picture that emerges is of carefully designed and functional buildings intended to sustain public, monumental, and practical functions. Section IV uses a variety of texts to examine the way in which libraries were viewed and used. Ch. IV. 1 discusses the evidence for use of libraries by scholars and authors such as Gellius, Galen, Josephus, and Apuleius. Ch. IV.2 examines parallels between library collections and compendious encyclopaedic elements within Roman literature and considers how library collections came to be canon-forming institutions and vehicles for the expression of imperial approval or disapproval towards authors. The channels through which this imperial influence flowed are investigated in Ch. IV.3, which looks at the directors and staff of the public libraries of Rome. The final section (V) of the thesis concerns public libraries outside the city of Rome. Provincial libraries provide a useful case study in 'Romanisation': they reveal a range of influences and are shown to embody local, personal, and metropolitan imperial identities. There follows a brief conclusion, and a bibliography. There are also five appendices of numismatic and epigraphic material discussed in the text. This material has not been adequately or completely gathered elsewhere and is intended to assist the reader; where appropriate it includes illustrations, transcriptions, and translations.
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Tighe, Stephen Patrick. "Macroscopic dislocation modelling." Thesis, University of Oxford, 1992. http://ora.ox.ac.uk/objects/uuid:e4f00d59-71b0-43c0-b141-0bb7e6108fff.
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Work-hardened metals typically possess large numbers of dislocations in complex three-dimensional configurations about which little is known theoretically. Here these large numbers of dislocations are accounted for by means of a dislocation density tensor, which is obtained by applying an averaging process to families of discrete dislocations. Some simple continuous distributions are examined and an analogy is drawn with solenoids in electromagnetism before the question of the equilibrium of dislocation configurations is studied. It is then proved that the only finite, simply-connected distribution of dislocations in equilibrium in the absence of applied stresses are ones in which all components of stress vanish everywhere. Some examples of these zero stress everywhere (ZSE) distributions are then given, and the concept of 'plastic distortion' is used to facilitate their interpretation as rotations of the crystal lattice. Plastic distortion can also be understood as a distribution of infinitesimal dislocation loops ('Kroupa loops'), and this idea is used in Chapter 4 to investigate the dislocation distributions which correspond to elastic inclusions. The evolution, under an applied stress, of some simple ZSEs is analysed, and the idea of 'polarisation' is introduced, again in analogy with electromagnetism. Finally, a mechanism is conjectured for the onset of plastic flow.
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Denney, Lisa. "Thin security? : the challenge of engaging informal security actors in DFID's security sector reform programme in Sierra Leone." Thesis, Aberystwyth University, 2013. http://hdl.handle.net/2160/2a246333-453e-4ee3-b714-7a53c3e9eeb7.
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The United Kingdom's Department for International Development (DFID) has undertaken a highly innovative development strategy in Sierra Leone, reforming the security sector of the post-conflict state in order to ensure a stable environment in which investment and development can occur. Yet in doing so, DFID has not engaged with the actual locus of security provision in Sierra Leone and the effectiveness of reforms thus remains limited. This thesis seeks to understand why DFID has been unable to engage with informal security actors in its security sector reform (SSR) programme in Sierra Leone. Informal security actors are the dominant providers of policing and justice in Sierra Leone, with approximately 80 per cent of the population relying upon their services. Despite this, however, this thesis illustrates that DFID's bureaucratic and political nature produce particular understandings of security and the causes of war that focus overwhelmingly on state capacity and security provision. As a result, DFID engages with only state security providers and state failure aspects of the causes of war. Ultimately, this approach limits the ability of DFID's SSR programme to comprehensively address the causes of conflict and sustainably transform security provision in Sierra Leone. These limitations must be overcome if DFID is to remain at the forefront of SSR policy and practice.
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Arenz, Christian. "Control of open quantum systems." Thesis, Aberystwyth University, 2016. http://hdl.handle.net/2160/263c2edb-bbab-46ac-b14e-961fea714d01.
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Known as decoherence, the unavoidable interaction of a quantum system with its surrounding environment is usually considered to be detrimental for quantum information processing. In this thesis the coherent, open loop control of such open systems is studied. Concepts from quantum control theory and the theory of open quantum system are adopted in order to fight decoherence and implement quantum gates in a noiseless manner. In particular, Lie algebraic methods and numerical optimization tools are used to investigate the control properties of a single spin interacting with a spin environment. We show that, independent of the size of the environment, every unitary transformation can be implemented on the system spin through a single control field. We proceed by investigating dynamical decoupling, a method to suppress the interactions with the environment, for finite- and for infinite dimensional systems. We prove that every finite dimensional system can be protected from decoherence, even if the environment is infinite dimensional, whereas for noise described by a Lindblad master equation dynamical decoupling will never succeed. This will lead to a new method to distinguish decoherence from intrinsic noise terms. We further prove that not every infinite dimensional system can be protected from decoherence through dynamical decoupling. Afterwards we investigate dynamical decoupling of systems that are described by quadratic Hamiltonians, showing that such interactions can always be suppressed with two simple operations. In the last part we investigate the coherent control of a Lindblad master equation. We show that a strong noise process exhibiting a decoherence free subspace can substantially increase the number of unitary operations that can be implemented, allowing us to fully control parts of the system. Afterwards we develop a scheme to make Hamiltonians and Lindbladians commutative by adding an auxiliary system. The old, possibly non-commutative dynamics, is recovered through a non-selective measurement.
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Pfannenschmidt, Sarah. "Blodeuedd and Bláthnait : a reassessment." Thesis, Aberystwyth University, 2009. http://hdl.handle.net/2160/7335e733-bc14-460e-b0e6-dbaa1259607b.
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In 1928, W.J. Gruffydd published his edition and findings on the Fourth Branch of the Mabinogi, Math vab Mathonwy. He proposed that the story of Blodeuedd, Lleu’s unfaithful wife and the woman created from flowers, was taken in part from the Irish story of the Munster hero Cú Roí mac Dáiri and his treacherous wife, Bláthnait. He further suggested that both Blodeuedd and Bláthnait’s stories derive from a lost common Irish source that is more closely represented by Bláthnait’s tale. He also reconstructed the Welsh story to appear more similar to his summarized form of the Irish tale, but neglected to discuss the complexity of the Irish tradition surrounding Cú Roí’s death tale. There are several points of resemblance between the texts. Both stories feature similar names for the women and the shared theme of an unfaithful wife who betrays her husband to his enemies. For her crime, the woman is punished and becomes an example of the consequences faced by unfaithful women. The Irish and Welsh stories also share a number of general motifs, but these motifs are not manifested using the same story details and are, therefore, better thought of as sub-motifs. Depending upon which versions of the Irish and Welsh stories are being analyzed, the same sub-motifs may or may not be shared between the texts. Gruffydd considers some of these factors, but he does not consistently acknowledge the existence of international examples of these motifs. Ultimately, his theories do not account for another possibility: that the stories may be analogues rather than borrowings. Therefore, it is the aim of this paper to reopen the question of the relationship between the tales of Blodeuedd and Bláthnait and to re-examine Gruffydd’s arguments regarding their possible connections. The first necessity is to distinguish between the versions of the Welsh and Irish stories and to examine the texts as they have survived. To that end, the Irish and Welsh stories are considered first within their own traditions before being subjected to an extended comparison. Clarifying the nature of the varying details and how they manifest within each tradition is crucial to determining the most likely nature of the stories’ relationship. The focus is primarily upon the sequence of events in each story, the wife’s role in these events, and any potential connections with common literary themes and folk motifs. Based upon the numerous differences between the texts, it is difficult to accept that the Welsh story is merely a copy of the Irish death tale of Cú Roí as Gruffydd supposed.
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Yi, X. "Electron microscopy study of radiation damage in tungsten and alloys." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:cb416551-164d-4290-b134-83278708ceff.
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The displacement damage induced by primary recoils of fusion neutrons in tungsten and alloys has been studied with self-ion irradiations, followed by damage characterization with electron microscopy. Tungsten and alloys (≤ 5 wt.% Re, Ta, V) were implanted with 2 MeV W+ ions over a dose range of 3.3×1017 - 2.5×1019 W+m-2 at temperatures ranging from 300 to 750°C. Dislocation loops of b = ½<111> (> 60%) and b = <100> were identified, and that ½<111> loops were found more thermally stable. Among loops that were large enough for nature determination, at least 50% were found to be of interstitial type, with larger fractions in high-temperature and high-dose conditions. The diameter of loops did not exceed 20 nm, with the majority being ≤ 5 nm. The loop number density varied between 1022 and 1023 m-3. The effects of ion dose, irradiation temperature, composition and grain orientation on damage microstructure were investigated. In-situ irradiations (150 keV W+ ions) were carried out as a complement to the bulk implantations. Qualitative trends in loop size, geometry and nature with irradiation dose and temperature were similar to bulk irradiated specimens. Also, the dynamics of defects and their effects on the damage evolution were explored. In-situ annealing of irradiated thin foils was performed to investigate the thermal stability of radiation damage in tungsten. The majority of microstructure transformations were completed within 15 min of annealing. However, extended durations did favour the increase of loop size and the fraction of ½<111> loops.
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Gregory, Charles T. "The end of Richelieu : noble conspiracy and Spanish treason in Louis XIII's France, 1636-1642." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:e730d78f-e11c-4f8d-b14f-f073924f3780.
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Cardinal Richelieu is traditionally accredited with defeating the power of the grands, the upper echelon of the French nobility, as part of his supposedly successful project for monarchical absolutism. Modern historians have recast Richelieu as a nobleman of his time, who advanced himself within the social and political hierarchies through marriage alliances and patronage. He therefore worked hard to forge alliances with the grands rather than trying to destroy them. Yet his ministry was riven by persistent noble conspiracies and rebellions, which have gone largely without systematic investigation. This study examines the nature and causes of that unrest during Richelieu’s final six years, offering a radical re-assessment of the opposition and the politics of the period. Noble conspiracy was not just a by-product of government by a first minister, but reflected the factional nature of Richelieu’s approach. Factional rivalry was exacerbated by the emergence, after 1638, of a struggle for the anticipated regency. After this, Richelieu took a more hostile approach to his adversaries, forcing them to adopt strong countermeasures in order to preserve their positions. Richelieu’s opponents were surprisingly successful in asserting their independence. As well as enjoying widespread domestic support, they allied with the Habsburg powers to engineer military rebellion, posing a major threat to the Cardinal and undermining the war effort against Spain. The Spanish set their stall out for a long-term war, expecting that Richelieu’s opponents would eventually gain power and negotiate peace on more flexible terms. The ability of the grands to re-assert themselves was still a dominant characteristic of French politics. Richelieu’s legacy, on his death in 1642, was a highly volatile political situation in which success was still a long way off for France. These findings suggest the catalytic impact of Habsburg power on France’s internal divisions, which should consequently be seen as integral to the forging of the ancien régime.
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Dragovic, Rebecca. "Measurement and characterisation of microvesicles and nanovesicles in pregnancy and pre-eclampsia." Thesis, University of Oxford, 2011. http://ora.ox.ac.uk/objects/uuid:cee47c16-f6f5-4264-b104-9e44987ade6f.
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Excessive release of syncytiotrophoblast vesicles (STBM) from the placenta into the maternal circulation may cause the inflammatory response, endothelial dysfunction and activation of the coagulation system characteristic of pre-eclampsia (PE). Consequently, other cell types including platelets, leukocytes, red blood cells (RBC) and endothelium may be activated to release cellular vesicles which exacerbate the disease. This thesis aimed to develop methodology for enumerating and phenotyping STBM and the other vesicle types to determine whether they could be used as biomarkers for PE. In vitro derived STBM and vesicles from the other cells of the vascular compartment were examined to select a suitable panel of antibodies to analyse these same vesicle types in plasma samples from non-pregnant (NonP), normal pregnant (NormP) and PE women. Our flow cytometer was shown to detect microvesicles ≥290nm, hence smaller nanovesicles and exosomes could not be detected by this method. Therefore, a novel technique for analysing both microvesicles and nanovesicles, Nanoparticle Tracking Analysis (NTA), was explored and was found to be able to detect vesicles as small as 70nm. The origins of the vesicles that change in pregnancy are not yet known. Flow cytometry and NTA were used in parallel to determine the size, number and phenotype of STBM and other cellular vesicles in NonP, NormP and PE women. Flow cytometry showed that majority of vesicles were derived from platelets, followed by RBC vesicles, leukocyte vesicles and STBM. NTA showed that the total number of vesicles in plasma was significantly elevated in NormP and late-onset PE women compared to NonP controls, and the vesicles were smaller in size. Similarly, flow cytometry showed differences in the composition of vesicles between pregnant and non-pregnant women, demonstrating that pregnancy affects vesicle release. However, no differences were found between NormP and PE women. This was probably due to the majority of samples studied being from late rather than early-onset PE. Thus, although this is the most comprehensive analysis of circulating vesicles in pregnancy to date, their use as biomarkers for PE remains an open question.
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Douglas, Sophie Georgina. "Regulation of CRAC channels and agonist-induced Ca2+ signals." Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:ae94ca14-ac95-4ea6-b14a-14f9f7bafd63.
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Calcium ions (Ca2+) are extremely important intracellular messengers, activating a plethora of cellular processes. Growing evidence now points to a major role for the local Ca2+ signal in driving specific cellular responses. The simplest and most fundamental local Ca2+ signal is the Ca2+ microdomain, which rapidly forms when Ca2+ permeable ion channels open. In non-excitable cells the dominant Ca2+ entry channels are store-operated Ca2+ channels (SOCCs). The best characterised is the Ca2+ release activated Ca2+ (CRAC) channel. How local Ca2+ entry through CRAC channels impacts on channel function however is unclear. I have investigated the interaction between the Ca2+ binding protein calmodulin and CRAC channel activity and subsequent agonist-induced Ca2+ signals. Furthermore, I have investigated a role for mitofusin 2 (a protein that is known to tether the ER and mitochondria) on these Ca2+ signals. Using three different calmodulin mutant constructs with alterations to their Ca2+ binding sensitivities, I have shown that calmodulin facilitates CRAC channel dependent Ca2+ entry and maintains agonist-induced cytosolic Ca2+ oscillations in a lobe-specific manner. Calmodulin has four Ca2+ binding sites, two on the N-lobe and two on the C-lobe. I found a dominant negative calmodulin mutant (CAM4M, where all four binding sites had been mutated), or one where the C-lobe could not bind Ca2+ (CAM2C), impaired both Ca2+ influx through CRAC channels and maintenance of cytosolic Ca2+ oscillations. In contrast, a Ca2+-insensitive N-lobe mutant had little effect, (CAM2N). Knockdown of the mitochondrial Ca2+ uniporter regulator (MICU1) or mitochondrial membrane depolarization had similar effects to those seen with CAM4M or CAM2C, suggesting that at least in part, the action of calmodulin was through regulation of mitochondrial Ca2+ dynamics. This was confirmed by directly measuring the mitochondrial matrix Ca2+ concentration in intact RBL-1 cells using the mitochondrial targeted, fluorescent protein, pericam. Both CAM4M and disruption of mitochondrial Ca2+ buffering impaired agonist-induced mitochondrial Ca2+ uptake, suggesting that the modulation of CRAC channels occurred through Ca2+-calmodulin facilitation of mitochondrial Ca2+ uptake. Using a mutant Orai1 (A73E) that cannot bind calmodulin, I have shown that calmodulin tethered to the CRAC channel provides a major source of calmodulin for effective mitochondrial Ca2+ uptake. Physiological relevance of my proposed pathway was provided from experiments where I showed knockdown of MICU1 impaired agonist-induced CRAC channel dependent NFAT-1-driven gene expression. In addition, I establish a crucial role for mitochondrial MFN2 and presumably its ability to properly link the mitochondria and ER in the control of CRAC channels and agonist-induced Ca2+ signals.
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Dahl, Andrew. "Methods to jointly analyze multiple phenotypes." Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:ed466a17-e96f-482b-b164-aa7ceefd94d4.
Full textAbstract:
Linear mixed models (LMMs) have re-emerged as a central tool in statistical genetics. Fixed effects capture genetic variants tested for association. Random effects leverage aggregate relatedness while remaining agnostic to specific genetic mechanisms, naturally modeling heritability and controlling for polygenic background and confounding from population or family structure in genome-wide association studies (GWAS). Multiple random effects can partition heritability amongst many biologically meaningful variance components (VCs). Concurrently, genetic studies have begun to analyze multiple traits. This can improve power by adding data and can inform the path from genotype to phenotype, e.g. with graphical models, pleiotropy detection or endophenotyping. Multi-trait analyses are natural for biobanks and high-throughput phenotypic measurements like gene expression, medical images or metabolites. Following these advances, this thesis develops three multi-trait mixed models. phenix imputes missing phenotype data by modifying probabilistic matrix factorization to incorporate genetic relatedness. General linear mixed models (GLMMs) generalize and unify multi-VC, multi-trait and likelihood-penalized mixed models. Finally, compressive mixed models (CMMs) combine the two, obtaining the imputation and computational benefits of phenix and the heritability estimation and multi-VC capabilities of GLMMs. phenix essentially always outperforms all competitors in imputation and can improve GWAS power. GLMMs accurately estimate heritability despite (measured) confounders, can improve phenotype prediction, and increase gene-based, multi-trait association signal. CMMs regularly improve prediction, scale to thousands of phenotypes, and can uncover plausible GWAS hits entirely missed by LMMs. Altogether, multi-trait mixed models are invaluable for intrinsically multitrait tasks, like phenotype imputation and low-rank decomposition, and, surprisingly, can be much faster than LMMs; however, I find only small, and inconsistent, benefits for single-trait-oriented objectives like heritability estimation and out-of-sample prediction. The challenges in this thesis are primarily computational. Naively, multi-trait approaches model an N × P matrix of P phenotypes measured on N samples as a long Gaussian vector, inducing prohibitive O(N3P3) computations. Fortunately, the parsimonious matrix normals underlying mixed models enable simpler O(N3+P3) expressions. This is summarized by a new decomposition for positive semidefinite tensor products that, under a crucial assumption, facilitates cheap evaluation of ubiquitous low-level operations like multiplication.
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Gudmundsson, Haraldur. "Cyclic alkenylsiloxanes : synthesis and application towards incednam." Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:b0c70071-ffda-44a9-bb14-69b2ded14f63.
Full textAbstract:
This thesis explores the use of cyclic alkenylsiloxanes in Hiyama cross-coupling reactions for the stereospecific construction of the Z-pentaenyl system of incednam, the aglycon of incednine. The early chapters continue the investigation of the previously developed C6-C13 lynchpin cyclic diethyl alkenylsiloxane, accessed by controlled semi-hydrogenation of alkynylsiloxane. Later chapters discuss the development of a novel strategy to access the more reactive cyclic dimethyl alkenylsiloxanes and their application towards the synthesis of incednam.
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O'Shea, Robert. "Not foreign to each other : Commonwealth Prime Ministers' Conferences, 1944-1969." Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:bace3d7e-fc31-4d1e-b145-1167b05ff45a.
Full textAbstract:
The Commonwealth Prime Ministers' Conferences were a unique experiment. They were an attempt at an intermediate mode of multilateral relations: members were no longer bound in an imperial hierarchy, nor were they fully foreign. A conscious effort was made to position the Commonwealth as a family, and the Conferences as their periodic reunion. Avoiding a 'diplomatic' culture at the Conferences in favour of a familial veneer allowed participants to claim that binding resolutions were not necessary and that meaningful cooperation could occur by consensus. This appeared to offer potential for forging a 'third way' between superpower blocs in a Cold War environment. This thesis makes an important contribution to the existing Commonwealth literature as the Conferences were the core structure of the Commonwealth until the formation of the Commonwealth Secretariat in 1965, yet have never been the subject of a full-length study. The thesis also engages with the concept of the 'British world', arguing that the Conferences had a major role in projecting British 'soft power' once martial or economic hegemony proved impracticable. By drawing on archival sources in eight Commonwealth countries, this thesis shows that the Conferences were effective in facilitating discussions on flashpoint topics such as white minority rule in South Africa and Rhodesia, even if the Commonwealth failed to fulfil hopes that it would remain an important international grouping. The study also has contemporary relevance, given that the Conferences continue as Commonwealth Heads of Government Meetings, and that questions of transnational identity and 'foreignness' continue to shape debates over Britain's relationship with Europe and its 'world role'.
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Roque, Paula Cristina. "The rebel governance of the SPLM/A and UNITA : a comparative study on parallel states in Angola and South Sudan." Thesis, University of Oxford, 2017. https://ora.ox.ac.uk/objects/uuid:fd5a65aa-2dcf-4699-b714-15f4d0e11dbb.
Full textAbstract:
This is a study of rebel political orders and the degree of governance rebels can install in their liberated areas. It studies the ways in which force came to be transformed into authority under the rule of two military organisations fighting asymmetrical wars in highly divided societies. Wartime rebel states are by nature an exercise in control and power, in projecting authority and symbolism, in managing contradictions and shortcomings, but are also deeply revealing of the characteristics of rebel movements, their motivations, survival strategies and organisational capacity. This thesis on the rebel governance of União Nacional para a Independência Total de Angola (UNITA) and the Sudan People's Liberation Movement/Army (SPLM/A) is a study on how two very different reform rebel movements, fighting two of Africa's deadliest and recurrent civil wars, devised and designed institutions to govern civilian populations in the stable liberated areas of Jamba in Angola and Yambio in South Sudan. Existing governing strategies were reformed after both faced critical junctures that exposed the fragilities of their organisations, the insufficient coordination of structures and leadership, and the need to reformulate an ideology to rally widespread support across constituencies. Their parallel states emerged as a key pillar to survive and win their second liberations. The Free Lands of Angola embodied UNITA's centralised and totalitarian state project. The New Sudan embodied the SPLM/A's decentralized approach to governance and its pragmatism of local alliances. This comparison is structured around four internal agentic elements of these two movements: their leadership, ideology/political program, organisation and approach to civilians. This allows for mutually reinforcing explanations of what informed their parallel states and contextualizes strategies and motivations by exposing a 'rebel-system' as a theory of operation accounting for change and highlighting elements that powered the movements and their liberation struggles.