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1

Begum, Ghazala. "Epigenetic changes in the hypothalamus of offspring following maternal undernutrition." Thesis, University of Manchester, 2014. https://www.research.manchester.ac.uk/portal/en/theses/epigenetic-changes-in-the-hypothalamus-of-offspring-following-maternal-undernutrition(d2254013-0981-4038-b901-55f94601afc2).html.

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Epidemiological studies show that offspring subjected to maternal undernutrition during early pregnancy are prone to developing obesity and other diseases in adulthood. The hypothalamic energy regulating pathway may be altered in these offspring, with epigenetic changes as a core mechanism. Therefore, this thesis aimed to determine if epigenetic changes are present in this pathway in the hypothalami from offspring subjected to maternal undernutrition. The investigations are focused on the glucocorticoid receptor (GR) as an inhibitor of the anorexigenic neuropeptide pro-opiomelanocortin (POMC), with potential modifications leading to increased food intake and the development of obesity. To achieve this, an established sheep model developed by our collaborators was used, during which maternal ewes were undernourished periconceptionally to produce a 10-15% decrease in body weight. We found that hypothalami from fetal offspring had greater epigenetic modifications when this reduction in maternal body weight was maintained from 60 days before conception until 30 days into pregnancy, with lower levels of POMC and GR promoter methylation. This was associated with increased GR mRNA expression. Other regions of the brain that also express POMC and GR, did not exhibit these epigenetic modifications. This study revealed that maternal undernutrition induces tissue specific epigenetic changes in fetal hypothalami which may contribute to disease in later life. Twins have been shown to have similar phenotypic characteristics as maternally undernourished offspring and therefore it has been suggested that they may also be programmed, but by intrauterine growth restriction. Consequently, extensive methylation and histone analysis of GR and POMC promoter regions was carried out in twin fetal hypothalami and compared to maternally undernourished groups. Interestingly, the decreased POMC and GR methylation of our amplicons in the maternally undernourished fetal hypothalami was also observed in twin fetal hypothalamic. This was concomitant with histone modifications and alterations in overall DNA methyltransferase activity. However, it was found that there were no changes in the POMC and GR mRNA expression levels in twin fetuses, but we postulate that this may occur later in life. To determine if changes in the fetal epigenetic status of hypothalamic GR and POMC impacted the adult progeny, tissues were obtained from adult offspring of maternally undernourished ewes. Epigenetic changes in the hypothalamic GR promoter observed in the fetal group persisted into adulthood, with concurrent increases in GR mRNA and GR protein expression. Of these groups the undernourished adult male offspring had decreased hypothalamic POMC expression and increased fat mass, changes that are consistent with an obese phenotype. The epigenetic and expression status of GR in the hippocampus and pituitary were modified, but in a tissue and sex specific manner. POMC epigenetic changes in the brain were complex, with various levels of epigenetic and expression changes. Overall periconceptional undernutrition induces hypothalamic specific changes in the epigenetic status of the GR gene which is known to regulate energy balance. Hypothalamic changes were persistent from the fetal stage into adulthood, with modifications in other tissues occurring after birth. These adaptations have the potential to increase the offspring’s propensity to develop obesity and altered stress regulation in later life.
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SOUZA, Adriana Ferreira de. "Produção simultânea de bioemulsificante e lipídeos por Candida lipolytica UCP 0988 utilizando substratos agroindustriais." Universidade Federal de Pernambuco, 2016. https://repositorio.ufpe.br/handle/123456789/26034.

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CNPq
Os biossurfactantes são compostos produzidos por bactérias, leveduras e fungos filamentosos, que apresentam na molécula uma porção hidrofóbica e outra hidrofílica, com potencial de redução da tensão superficial da água e ou emulsificação, sendo estes denominados de bioemulsificantes. Os micro-organismos que apresentam habilidade de acumular a partir de 20% em relação ao seu peso seco, são denominados oleaginosos, considerados como fontes promissoras para a produção de biodiesel. Neste sentido, estudos foram realizados com a Candida lipolytica UCP0988, no estado anamorfo, investigando a produção simultânea de bioemulsificante e lipídeos, empregando como substratos alternativos óleo de soja pós-fritura e milhocina, utilizando um planejamento fatorial de 2². O cultivo foi realizado em Erlenmeyers contendo 100 mL do meio de produção de acordo com o planejamento, com 1% de inoculo de 10⁷ cel/mL, incubados a 28ºC, 150 rpm por 96h. O bioemulsificante foi produzido no líquido metabólico livre de células, avaliado pela atividade e índice de emulsificação, caracterizado pelo tamanho das partículas, estabilidade com relação à diferentes pH, NaCl e altas temperaturas, teste de deslocamento de óleo (ODA) e aplicação na remoção de poluente hidrofóbico. Da biomassa obtida foi avaliada a acumulação de lipídeos, seguido a extração, transesterificação e caracterização dos ácidos graxos por cromatografia gasosa. Os resultados demonstraram que o bioemulsificante foi produzido no final da fase exponencial com 6,704 Unidades de atividade de emulsificação (UAE) em hexadecano e índice de emulsificação de 96,66% com o óleo queimado de motor na condição 4 do planejamento (milhocina 5% e óleo de soja pós-fritura 8%), com a formação de emulsão estável em todas as temperaturas, em pH 2 e 4 com 2% de salinidade e capacidade de remover 93,74% do óleo diesel. Além disso, o bioemulsificante demonstrou propriedade dispersante após o deslocamento de 45,34 cm² do óleo na condição do ponto central do planejamento. A biomassa de C. lipolytica mostrou acúmulo de lipídios observado por citoquimica, obteve 42,00% de lipídios totais e sendo 96,7% deles correspondentes a ésteres metílicos de ácidos graxos. A Candida lipolytica apresentou boa produção de bioemulsificante e biodiesel usando conversão metabólica dos resíduos agroindustriais, tornando o bioprocesso econômico e com grande potencial na aplicação biotecnológica.
Biosurfactants are compounds produced by bacteria, yeasts and filamentous fungi, which have in the molecule a hydrophobic portion and one hydrophilic, with a potential for reducing the surface tension of water and/or emulsification, these being called bioemulsifiers. However, some microorganisms having ability to accumulate 20% or more of lipids in relation to its dry weight are called oleaginous, considered as main sources for production of biodiesel. In this respect, studies have been carried out with the yeast Candida lipolytica UCP0988, at anamorph state, investigating the simultaneous production of bioemulsifier and lipids, using as alternative substrates post-frying soybean oil and corn steep liquor, employing a 2² factorial design. Cultivation was carried out in Erlenmeyer flasks containing 100 mL of the production medium according the experimental design, with 1% inoculum (10⁷ cells/mL), incubated at 28°C, 150 rpm for 96h. The bioemulsifier was produced in the cell-free metabolic liquid, assessed the emulsifying activity and index, characterized by particle size, stability against pH, NaCl and temperature, oil displacement test (ODA) and application to removal hydrophobic pollutant. Accumulation of lipids was evaluated from the biomass, followed by extraction and characterization of fatty acids by gas chromatography. The results showed that the bioemulsifier was produced in the late exponential phase with 6.704 units of emulsification activity (UEA) and index de 96,66% at condition 4 of factorial design (corn steep liquor 5% and post-frying soybean oil 8%), stable emulsion in all temperatures, at pH 2 and 4 and 2% salinity were formed, and ability to removing 93,74% of diesel oil in sand. The results with displacement oil showed 45.34 cm² of dispersion (central point of the design). The biomass of C. lipolytica showed lipid accumulation observed by Sudan Black staining technique, which 42% of total lipids, and 96.70% of them corresponding to fatty acids methyl esters. C. lipolytica demonstrated the ability to produce both bioemulsifier and lipids using metabolic conversion of corn steep liquor and post-frying soybean oil agroindustrials residues, making economic bioprocess and with great application potential to environmental biotechnology.
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3

Santana, Willma José de. "Produção de biossurfactante por Candida lipolytica (UPC 0988) utilizando óleo de pequi como fonte alternativa de Carbono." Universidade Federal de Pernambuco, 2012. https://repositorio.ufpe.br/handle/123456789/12754.

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CNPq
A produção de biossurfactantes tem sido amplamente investigada nos últimos anos, considerando seu potencial biotecnológico e suas aplicações nos mais diversos setores industriais. O objetivo desta pesquisa foi à produção de biossurfactante por Candida lipolytica (UCP 0998), utilizando óleo da amêndoa e do endocarpo do pequi como fonte alternativa de carbono durante 72 horas a 150 rpm e 28º C através de planejamentos fatoriais. No primeiro planejamento fatorial completo 22 foram utilizadas as variáveis óleo da amêndoa e do endocarpo do pequi e glicose. Os resultados com o óleo da amêndoa do pequi, demonstraram uma tensão superficial de 30,51 mN/m, no ensaio 4 (20% de óleo e 1% de glicose), o melhor índice de emulsificação foi obtido com óleo de canola 50%, a produção de biomassa foi de 0,4396g/L. As atividades enzimáticas produzidas pela Candida lipolytica para esterase foi de 30mm e para lípase 15mm. Para óleo do endocarpo do pequi verificou-se a menor tensão superficial 31,96 mN/m, no ensaio 3 (10% de óleo e 1% de glicose), com o melhor índice de emulsificação com óleo de milho de 50%, a produção de biomassa foi 0,5107g/L. As atividades enzimáticas esterase foi de 23mm e de lípase 15mm. Foi realizado um segundo planejamento fatorial meia fração 2 5-1 selecionando o óleo da amêndoa do pequi para aumentar a produção do biossurfactante, onde as variáveis avaliadas foram 5% da amêndoa do pequi, 1% de glicose, pH= 4,5, inoculo 107 e meio mineral (2:1 v/v) água do mar e água destilada tendo como variáveis resposta tensão superficial, índice de emulsificação e atividade de emulsificação. Os resultados obtidos demonstraram que o biossurfactante apresentou uma tensão superficial 27,66 mN/m, no ensaio 11 (5% de óleo da amêndoa do pequi e 1% de glicose), índice de emulsificação 27%, atividade de emulsificação 3,790 U.A.E. A partir do melhor resultado do planejamento fatorial 25-1, um novo planejamento fatorial 22 foi realizado, com a finalidade de otimizar o meio de produção do biossurfactante. Os resultados demonstraram que o ensaio 6 (4% de óleo e 2% de glicose), apresentou a menor tensão superficial 30,32 mN/m e um índice de emulsificação de 31%. A estabilidade do biossurfactante foi verificada sob condições especifícas de pH, temperatura e concentrações de NaCl utilizando como parâmetro o índice de emulsificação. Os resultados demonstraram que o pH = 12 emulsificou 89%, 8g de NaCl 34% e a temperatura a 0º C 70%. A aplicação do biossurfactante foi avaliada na remoção de areia contaminada com petróleo utilizando um tratamento com condições pré-estabelecidas 5% da amêndoa do pequi, 1% de glicose, pH= 4,5, inoculo 107 e meio mineral (2:1 v/v) água do mar e água destilada, após 32 horas ocorreu uma remoção de 58,17%, o melhor índice de emulsificação ocorreu com 8 horas 29,41% utilizando óleo de milho e com 24 horas 25,80% utilizando óleo de canola. Não houve formação de emulsão quando foi utilizado n-hexadecano. O biossurfactante produzido por Candida lipolytica cultivada em óleo de pequi, representa uma alternativa de produção de um biopolímero com perspectivas para aplicações nas indústrias farmacêuticas, cosméticas e em biorremedição de solos contaminados por óleos.
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4

Andreas, Martin, Lorenz Kuessel, Stefan Wirth, Kathrin Gruber, Franziska Rhomberg, Fatemeh Gomari-Grisar, Maximilian Franz, Harald Zeisler, and Michael Gottsauner-Wolf. "Bioimpedance cardiography in pregnancy: A longitudinal cohort study on hemodynamic pattern and outcome." Springer Nature, 2016. http://dx.doi.org/10.1186/s12884-016-0918-8.

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Background: Pregnancy associated cardiovascular pathologies have a significant impact on outcome for mother and child. Bioimpedance cardiography may provide additional outcome-relevant information early in pregnancy and may also be used as a predictive instrument for pregnancy-associated diseases. Methods: We performed a prospective longitudinal cohort trial in an outpatient setting and included 242 pregnant women. Cardiac output and concomitant hemodynamic data were recorded from 11th-13th week of gestation every 5th week as well as at two occasions post partum employing bioimpedance cardiography. Results: Cardiac output increased during pregnancy and peaked early in the third trimester. A higher heart rate and a decreased systemic vascular resistance were accountable for the observed changes. Women who had a pregnancy-associated disease during a previous pregnancy or developed hypertension or preeclampsia had a significantly increased cardiac output early in pregnancy. Furthermore, an effect of cardiac output on birthweight was found in healthy pregnancies and could be confirmed with multiple linear regression analysis. Conclusions: Cardiovascular adaptation during pregnancy is characterized by distinct pattern described herein. These may be altered in women at risk for preeclampsia or reduced birthweigth. The assessment of cardiac parameters by bioimpedance cardiography could be performed at low costs without additional risks.
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Rice, Linda J. "The biblical view of reactive attachment disorder." Santa Clarita, CA : The Master's College, 2006. http://dx.doi.org/10.2986/tren.091-0077.

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Coyle, Rachel Lynn. "Women and pornography, an examination of the problem and how to help them find freedom." Theological Research Exchange Network (TREN) Access this title online, 2006. http://dx.doi.org/10.2986/tren.091-0041.

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Rogers, Andrew D. "Calling sons to a life worth living a father and son study through Ecclesiastes." Theological Research Exchange Network (TREN), access this title online, 2006. http://dx.doi.org/10.2986/tren.091-0050.

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Bertelsen, Michelle. "A biblical perspective on euthanasia." Theological Research Exchange Network (TREN), access this title online, 2006. http://dx.doi.org/10.2986/tren.091-0053.

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Curran, Peggy E. "A biblical perspective on anorexia nervosa, workbook for teens and young adults." Theological Research Exchange Network (TREN), access this title online, 2006. http://dx.doi.org/10.2986/tren.091-0054.

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Isaacs, Victoria MacKenzie. "Preaching during the interim a transitional ministry lectionary centered on the table /." Denver, CO : Iliff School of Theology, 2008. http://dx.doi.org/10.2986/tren.098-0026.

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Davis, John Paul. "Performers of the faith an image for the church and a direction for homiletics /." Denver, CO : Iliff School of Theology, 2008. http://dx.doi.org/10.2986/tren.098-0025.

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Hahn, Zintack Albert. "Preaching on difficult passages in Mark's gospel based on performance criticism." Denver, CO : Iliff School of Theology, 2008. http://dx.doi.org/10.2986/tren.098-0022.

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Geslin, Daniel. "In search of a queer homiletic." Denver, CO : Iliff School of Theology, 2008. http://dx.doi.org/10.2986/tren.098-0027.

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Overley, Amy. "Overcoming abuse." Santa Clarita, CA : The Master's College, 2004. http://dx.doi.org/10.2986/tren.091-0031.

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Pollinger, Millicent M. "A woman's call to loving others through social graces." Santa Clarita, CA : The Master's College, 2006. http://dx.doi.org/10.2986/tren.091-0059.

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Mario, Erica Guilhen. "Ação do agonista não-peptídico da angiotensina-(1-7), AVE 0991, nas alterações metabólicas induzidas por suplementação com frutose." Universidade Federal de Minas Gerais, 2012. http://hdl.handle.net/1843/BUOS-96EHGK.

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Recent studies have shown that activation of angiotensin-(1-7) / receptor Mas axis plays important role in intermediary metabolism, evidenced by increase in insulin sensitivity. The compound AVE 0991 is a non-peptide angiotensin-1-7 agonist, which effects in intermediary metabolism has not yet been studied. Thus, the objective of this study was to evaluate the action of this agonist on the metabolic changes induced by fructose supplementation. Male Sprague-Dawley rats at 5 weeks of age were utilized. The animals were divided randomically into four groups: Group C: animals fed a commercial diet (control) plus vehicle; Group CA: animals fed a commercial diet treated plus AVE 0991 (gavage at 1mg/kg concentration), Group F: animals fed a commercial diet supplemented with 10% fructose in the drinking water treated plus vehicle; Group FA: animals fed a commer cial diet supplemented with 10% fructose in the drinking water treated plus AVE 0991 (gavage at 1mg/kg concentration). Fructose supplementation promoted glucose intolerance and treatment with AVE 0991 reversed this parameter, besides increasing the hepatic glycogen content and reduces serum levels of insulin, triacylglycerols and non-esterified fatty acids. In addition, in the fructose group, total lipids and triacylglycerols secretion by liver were increased and AVE0991 treatment decreased these parameters . In muscle and adipose tissue, the treatment increased the activity of lipoprotein lipase (LPL), and the expression of genes involved in lipid oxidation such as PPAR and CPT-1 were increased. In adipose tissue, the PPAR gene expression, involved in fat deposition and improvement of insulin sensitivity showed no increase in adipose tissue mass. These results suggest that activation of Mas receptor by AVE 0991 agonist seems to be involved in the improvement of deleterious changes promoted by fructose supplementation.
Estudos recentes demonstram que a ativação do eixo angiotensina-(1-7)/receptor Mas, exerce papel importante no metabolismo intermediário, evidenciado pelo aumento da sensibilidade à insulina. O composto AVE 0991 é um agonista não -peptídico da angiotensina-1-7, cujos efeitos sobre o metabolismo intermediário ainda não foram estudados. Desta forma, o objetivo do presente trabalho foi avaliar a ação deste agonista sobre as alterações metabólicas induzidas pela suplementação com frutose. Para isso foram utilizados ratos machos Sprague-Dawley com 5 semanas de idade. Os animais foram divididos em grupo controle (C) que recebeu dieta comercial e grupo frutose (F) que foi alimentado com dieta comercial e suplementados com 10% de frutose na água de beber. Após 3 semanas de suplementação com frutose os animais foram subdivididos e tratados durante 2 semanas por gavagem com veículo (grupos C e F) ou tratados com AVE 0991 na concentração de 1mg/Kg de PC (grupos CA e FA). A suplementação com frutose promoveu uma intolerância à glicose e o tratamento com AVE 0991 reverteu esse parâmetro, além de aumentar o conteúdo hepático de glicogênio e reduzir os níveis séricos de insulina, triacilgliceróis e de ácidos graxos não -esterificados. Além disso, o grupo que recebeu apenas frutose apresentou um teor aumentado de lipídios totais no fígado, o qual foi acompanhado por aumento da secreção hepática de triacilgliceróis enquanto o tratamento com AVE 0991nos animais suplementados com frutose reduziu tanto o conteúdo de lipídi os totais quanto a secreção hepática de triacilgliceróis. No músculo e no tecido adiposo o tratamento com o agonista do receptor Mas aumentou a atividade da lipase lipoproteíca (LPL), sendo que no músculo houve um aumento da expressão de genes envolvidos na oxidação lipídica, como PPAR e CPT-1, enquanto que no tecido adiposo houve um aumento da expressão gênica PPAR, envolvido na deposição de lipídica e na melhora da sensibilidade a insulina, entretanto não houve aumento da massa do tecido adiposo. Esses resultados sugerem que a ativa ção do receptor Mas pelo agonista AVE 0991 parece estar envolvida na melhora das alterações deletérias promovida pela suplementação com frutose.
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Leite, Karla Carneiro de Siqueira. "Caracterização eletroquímica do composto LQFM-091, obtido por hibridação molecular a partir dos protótipos nimesulida e BF-389." Universidade Federal de Goiás, 2015. http://repositorio.bc.ufg.br/tede/handle/tede/5380.

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Nimesulide is an anti-inflammatory drug (NSAID) whose preferential selectivity for cyclooxygenase-2 (COX-2) leads to fewer adverse effects and wide use. Nimesulide, like other NSAIDs and selective COX-2 by inhibiting a single metabolic pathway of the arachidonic acid cascade are still responsible for gastrointestinal and cardiovascular side effects. However, recent studies show that the development of multi-targeted anti-inflammatory is an important strategy for obtaining the most effective drugs with fewer side effects. Therefore, the molecular changes from nimesulide has been proposed as a molecular hybridization with a derivative of butylhydroxytoluene BF-389. Such molecular modification products aim to inhibit metabolic pathways of two cascade of arachidonic acid, COX-2 and via the 5-lipoxygenase (LOX). Within the search string and development of new candidate drugs presenting prototypes of electroactive subunits, the characterization of the redox profiles can be made through the electrochemical techniques, which are characterized by speed, low cost and simplicity. In the electrochemical characterization of a new candidate prototype was observed two peaks with anode potential of 1.0V 0,42V and due to oxidation of aromatic amine and phenolic hydroxyl respectively. After analysis by varying the pH and scanning speed, it follows that mass transfer occurs via diffusion processes and proton transfer. The electrochemical analyzes, and are a supplementary means of characterization, were conclusive to prove that the electroactive groups are important in drug mechanism of action, remain free and yet, via a calibration curve constructed by measuring the current (i) due to the potential different concentrations of analyte, one can demonstrate the ability to dispense the new drug candidate developed.
A nimesulida é um fármaco anti-inflamatório não esteroidal (AINE) cuja seletividade preferencial à cicloxigenase-2 (COX- 2) leva à redução de efeitos adversos e amplo uso. A nimesulida, assim como outros AINES e os inibidores seletivos de COX-2 ao inibirem uma única via da cascata metabólica do ácido araquidônico ainda são responsáveis por efeitos colaterais gastrintestinais e cardiovasculares. Entretanto, estudos recentes mostram que o desenvolvimento de anti-inflamatórios multi-alvos representa uma importante estratégia para a obtenção de fármacos mais eficazes e com menos efeitos colaterais. Por isso, modificações moleculares a partir da nimesulida tem sido propostas como a hibridação molecular com um derivado do butilhidroxitolueno o BF-389. Tais produtos de modificação molecular têm a finalidade de inibir duas vias da cascata metabólica do ácido araquidônico, a COX-2 e a via da 5-lipo-oxigenase (LOX). Dentro da cadeia de pesquisa e desenvolvimento de novos candidatos a protótipos de fármacos que apresentem subunidades eletroativas, a caracterização dos seus perfis redox pode ser feita através das técnicas eletroquímicas, que se destacam pela rapidez, baixo custo e simplicidade. Na caracterização eletroquímica de um novo candidato a protótipo foi observado dois picos com potenciais anódicos de 0,42V e 1,0V devido à oxidação da amina aromática e da hidroxila fenólica, respectivamente. Após as análises variando o pH e a velocidade de varredura, conclui-se que a transferência de massa ocorre através de processos difusionais e com transferência de prótons. As análises eletroquímicas, além de serem um meio complementar de caracterização, foram conclusivas para se comprovar que os grupos eletroativos, importantes no mecanismo de ação de fármacos, permanecem livres e ainda, através da curva de calibração construída com a medida da corrente (i) em função do potencial em diferentes concentrações do analito, pode-se demostrar a possibilidade de se dosificar o novo candidato a fármaco desenvolvido.
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Blecha, Andreas. "Gentechnisches Design bakterieller Hüllproteine für die technische Nutzung." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2005. http://nbn-resolving.de/urn:nbn:de:swb:14-1136195910253-09581.

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Als "surface-layer" (S-Layer, SL) bezeichnet man die regelmäßig strukturierten Hüllproteinlagen auf der Oberfläche von etwa 80 % aller bisher bekannten Bakterienspezies. Sie entstehen durch Selbstassemblierung von identischen Proteinuntereinheiten, die wiederum zumeist durch nichtkovalente Wechselwirkungen mit der darunterliegenden Zellwandkomponente verknüpft sind. Trotz ihrer Diversität auf der Ebene der Primärstruktur weisen S-Layer verschiedener Bakterienarten einheitliche physikochemische Merkmale auf. Dazu zählt u.a. die Wiedereinnahme einer hochgradig strukturierten, porösen Proteinschicht nach reversibler Denaturierung. Infolge der Reassemblierung entstehen sowohl in Lösung als auch an Phasengrenzen Proteinassemblate, deren Porenanordnungen die gleiche regelmäßige Symmetrie aufweisen, wie die nativen Hüllproteine auf der Bakterienzelle. Das in seiner Domänenstruktur aufgeklärte Hüllprotein SbsC des mesophilen Bakterienstammes Geobacillus (G.) stearothermophilus ATCC 12980 zeichnet sich durch eine ausgezeichnete Synthetisierbarkeit in E. coli aus. C-terminale Fusionen, die im Falle des verstärkt grün fluoreszierenden Proteins (EGFP) bis zu 240 Aminosäuren umfassen, führten nicht zu einem Verlust der Selbstassemblierung. Darüber hinaus zeigen in vitro gebildete SbsC-Assemblate eine außergewöhnliche Stabilität gegenüber hohen Ethanolkonzentrationen. Die durch gerichtete Mutagenese erzeugten SbsC-Fusionsproteine SbsC(aa 31-1099)-HspA und SbsC(aa 31-1099)-12His besitzen in assemblierter Form im Vergleich mit dem unmodifizierten Protein eine bis zu zweimal höhere Bindungsaffinität gegenüber Platinionen. In denaturierter Form waren beide Fusionsproteine in der Lage, Nickelionen zu komplexieren. In der vorliegenden Arbeit wurde erstmals ein SL-Protein in einem eukaryontischen Mikroorganismus produziert. Das in der Hefe S. cerevisiae gebildete Fusionsprotein SbsC(aa 31-1099)-EGFP assembliert dabei im Cytosol der Wirtszellen zu röhrenförmigen Assemblaten mit regelmäßiger Symmetrie. Das bisher unbekannte SL-Protein des Stammes G. stearothermophilus DSM 13240 wurde erfolgreich heterolog in E. coli exprimiert. Die Vorläuferform besitzt im Vergleich zum maturen Protein ein 31 aa umfassendes Sekretionssignal am extremen N-Terminus. Sowohl das authentische Protein als auch das heterolog in E. coli exprimierte Vorläuferprotein zeigen eine dem SbsC-Protein vergleichbare Reassemblierungscharakteristik. Im Gegensatz dazu führte die Verkürzung der N-terminalen 30 Aminosäuren des als S13240 bezeichneten Hüllproteins im heterologen System zu einem irreversiblen Verlust der Fähigkeit zur Selbstassemblierung.
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Ballester, Riesco Benjamín. "Tecnología y vida social de los instrumentos líticos de los primeros cazadores, recolectores y pescadores costeros del semiárido. El caso de Punta Ñagué (LV-098A)." Tesis, Universidad de Chile, 2015. http://repositorio.uchile.cl/handle/2250/136510.

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20

Howald, Claudia. "Kinder mit Autismus im stationären Bereich." Bern Ed. Soziothek, 2005. http://www.soziothek.ch/?3-03796-098-1.

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21

Geremia, Alessandra. "The role of the IL23/IL17 pathway in inflammatory bowel disease." Thesis, University of Oxford, 2011. http://ora.ox.ac.uk/objects/uuid:f39c2ab5-098e-45d8-a800-e4c4bc7ae85f.

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The aetiology of IBD is unknown, but available evidence suggests that an aberrant immune response towards the commensal microbial flora is responsible for intestinal inflammation in genetically susceptible individuals. Studies from animal models of intestinal inflammation have greatly advanced our understanding of the immunological basis of IBD. However, translation of results from animal research into human studies is essential in order to improve treatment options and patient quality of life. In this thesis we present the successful introduction of translational studies on human tissue in our laboratory. In particular, we evaluated the role of the IL23/IL17 pathway in the human immune response and its role in IBD. IL23-driven inflammation has been primarily linked to its activity on Th-17 cells; however, work from our laboratory has identified a novel population of IL23-responsive ILC, which are responsible for innate colitis in mice. Here we have analyzed the role of IL23-responsive innate cells in IBD. Our results show increased expression of Th-17 signature genes amongst intestinal CD3- cells in patients with IBD. Furthermore, we observed a marked and selective increase in IL17 producing CD56- ILC in the inflamed intestine of patients with CD. ILC may contribute to intestinal inflammation through secretion of cytokines, such as IL17A and IL17F, and recruitment of other inflammatory cells, representing a novel tissue-specific target for the treatment of IBD. In addition, we present here our preliminary data on the characterization of human intestinal and systemic DC populations. In particular, we aimed to evaluate if in the context of the intestinal microenvironment DC develop specific regulatory features, as observed in murine CD103+ DC. We show that human intestinal DC populations exhibit specific regulatory properties, such as expression of genes associated with TGF-β and RA activity. Furthermore, CD103+ DC are present in the human gut and are characterized by tolerogenic markers. Remarkably, patients with IBD have reduced frequencies of intestinal CD103+ DC, which display a more pro-inflammatory phenotype. Alteration in DC subset composition and functional activity may result in a distort balance between immune effector and regulatory responses, promoting the development of intestinal inflammation.
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Muehlemann, Anton. "Variational models in martensitic phase transformations with applications to steels." Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:bb7f4ff4-0911-4dad-bb23-ada904839d73.

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This thesis concerns the mathematical modelling of phase transformations with a special emphasis on martensitic phase transformations and their application to the modelling of steels. In Chapter 1, we develop a framework that determines the optimal transformation strain between any two Bravais lattices and use it to give a rigorous proof of a conjecture by E.C. Bain in 1924 on the optimality of the so-called Bain strain. In Chapter 2, we review the Ball-James model and related concepts. We present some simplification of existing results. In Chapter 3, we pose a conjecture for the explicit form of the quasiconvex hull of the three tetragonal wells, known as the three-well problem. We present a new approach to finding inner and outer bounds. In Chapter 4, we focus on highly compatible, so called self-accommodating, martensitic structures and present new results on their fine properties such as estimates on their minimum complexity and bounds on the relative proportion of each martensitic variant in them. In Chapter 5, we investigate the contrary situation when self-accommodating microstructures do not exist. We determine, whether in this situation, it is still energetically favourable to nucleate martensite within austenite. By constructing different types of inclusions, we find that the optimal shape of an inclusion is flat and thin which is in agreement with experimental observation. In Chapter 6, we introduce a mechanism that identifies transformation strains with orientation relationships. This mechanism allows us to develop a simpler, strain-based approach to phase transformation models in steels. One novelty of this approach is the derivation of an explicit dependence of the orientation relationships on the ratio of tetragonality of the product phase. In Chapter 7, we establish a correspondence between common phenomenological models for steels and the Ball-James model. This correspondence is then used to develop a new theory for the (5 5 7) lath transformation in low-carbon steels. Compared to existing theories, this new approach requires a significantly smaller number of input parameters. Furthermore, it predicts a microstructure morphology which differs from what is conventionally believed.
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England, Katherine Sara. "A potent and selective inhibitor of a histone demethylase." Thesis, University of Oxford, 2015. https://ora.ox.ac.uk/objects/uuid:e078e629-0987-449b-96dc-748601f2cff3.

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Post-translational modifications (PTMs) to histone proteins play important roles in the regulation of gene expression. Histone lysine demethylases (KDMs) remove methyl groups from N?-amino methylated lysine residues. There are two classes of human KDMs; the flavin adenosine dinucleotide-dependent demethylases (the KDM1 subfamily) and the 2-oxoglutarate- (2OG) dependent Jumonji C (JmjC) demethylases (KDM2-7). Misregulation and mutation of histone demethylases are associated with multiple human diseases including cancer. Hence potent and selective inhibitors are of interest for investigations into the biological roles of KDMs and their relevance as targets for drug discovery. JmjC KDM inhibitors have been reported in the literature but there are few subfamily selective examples. The aim of the work described in this thesis was to design and synthesise potent and subfamily selective inhibitors of human JmjC KDMs for use as chemical probes. An aminomethyl pyridine-4-carboxylate series that was derived from a high throughput screening hit delivered a selective, submicromolar KDM2A inhibitor. X-ray crystallographic analyses demonstrated that the aminomethyl pyridine moiety bound the active site iron revealing a novel JmjC KDM inhibitor scaffold. A known 2,2'-bipyridine-4-carboxylate scaffold was used as a starting point for the identification of a second, novel JmjC KDM inhibitor series that contains a triazolopyridine moiety as a replacement for the bipyridine system. The triazolopyridine core was shown to bind in the 2OG binding site of KDM4A by X-ray crystallography. Optimisation of the triazole substituent gave a selective inhibitor of KDM2A/7B that is significantly more potent (KDM2A IC50: 58 nM, KDM7B IC50: 150 nM) than reported KDM2/7 subfamily selective inhibitors. As for many other JmjC KDM inhibitors, this compound was not found to be efficacious in a cellular assay. A variety of strategies were pursued with the aim of improving the cellular efficacy. However, only a modest effect was observed in the cellular assay (less than 25% inhibition at 100 μM). A biotinylated analogue was immobilised onto streptavidin-coated beads for chemoproteomics experiments and was found to interact with KDM2A in cell lysate. Overall, this work resulted in the identification of two new scaffolds for JmjC KDM inhibition and in a potent and selective inhibitor of KDM2A/7B.
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Liu, Yang. "Privacy-preserving targeted advertising for mobile devices." Thesis, University of Oxford, 2017. http://ora.ox.ac.uk/objects/uuid:c2c929cc-0931-457a-afff-d973624a356c.

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With the continued proliferation of mobile devices, the collection of information associated with such devices and their users - such as location, installed applications and cookies associated with built-in browsers - has become increasingly straightforward. By analysing such information, organisations are often able to deliver more relevant and better focused advertisements. Although such Targeted Mobile Advertising (TMA) offers great benefits to advertisers, it gives rise to a number of concerns, with privacy-related concerns being prominent amongst them. It follows that there is a need for an advertisement-selection mechanism that can support the existing TMA business model in a manner that takes into account consumers' privacy concerns. The research described in this dissertation explores the delicate balance between the goals of the advertisers and the consumers: advertisers pursue profits by applying TMA, which violates consumers' privacy; consumers hope to benefit from useful mobile advertisements without compromising their personal information. The conflicts of interests between consumers and advertisers in the context of targeted mobile advertising brings us to our research question: Is it possible to develop a privacy-preserving TMA framework that enables mobile users to take advantage of useful advertising services without their privacy being compromised, and without impacting significantly advertising effectiveness? In order to answer this question, this dissertation presents four main contributions. First, we report upon the result of a qualitative study to discuss the balance that needs to be struck between privacy and utility in this emerging area. Second, a number of formal models are developed to reason about privacy, as well as to reason about the relationship between privacy and utility in the context of TMA. Third, a novel ad-selection architecture, PPTMA (Privacy-Preserving Targeted Mobile Advertising), is presented and evaluated. Finally, a privacy-preserving advertisement-selection mechanism, AdSelector, is introduced. The mechanism is novel in its combination of a user subscription mechanism, a two-stage ad-selection process, and the application of a trustworthy billing system.
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Pullen, Anne Jennifer. "Behavioural indicators of candidate enrichments for kennel housed dogs." Thesis, University of Bristol, 2011. http://hdl.handle.net/1983/add992d2-09f1-4658-aedf-93198b620b3d.

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The welfare of kennelled dogs is often considered to be suboptimal and therefore to require "enrichment". This thesis examines the short-term reactions of dogs to a variety of potential enrichments. Where possible, comparisons were also made between two contrasting kennel environments, to indicate to what degree interest in enrichments is influenced by environment, as well as fulfilling species requirements. Interaction with toys was investigated as an example of inanimate enrichment. Toys that made a noise and/or could be chewed easily were found to be preferred to more robust toys, suggesting that the latter may provide little enrichment. Interactions with humans and conspecifics were investigated as examples of animate enrichment. Dogs in long-stay enriched (LSE) kennels preferred unfamiliar humans to familiar, while those in rehoming (RH) kennels showed no overall preference: therefore, the welfare benefit of different forms of human contact is likely to differ between facilities. LSE dogs also behaved differently depending upon the familiarity of conspecifics, with the greeting period at the beginning of the interaction more important for unfamiliar dogs, suggesting that familiarity is also an important factor when considering the effectiveness of conspecific contact as enrichment. Comparing animate and inanimate enrichments, LSE dogs chose social contact (human or dog) over toys. However, their greatest interest was in the goings-on outside the pen. The rapid habituation that occurs towards individual objects during play was shown, by measuring dishabituation, to be due to the overall stimulus properties of the toy rather than those within any single sensory modality. The time interval between presentations did not appear to be critical to habituation or dishabituation. Behaviour indicating a switch from anticipation to frustration as enrichment is delayed was investigated but not determined. However, positive reinforcement training may have inhibited expression of frustration behaviour.
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Shu, Chi-Kou. "Computing exact approximations of a Chaitin omega number." Thesis, University of Auckland, 2004. http://hdl.handle.net/2292/38.

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A Chaitin Omega number, Ω, is the halting probability of a universal Chaitin (self-delimiting Turing) machine. Every Ω number is both computably enumerable and random. In particular, every Ω number is non-computable. In this thesis, we describe a method to compute the exact values of the first 64 successive bits of a natural Chaitin Omega number. We first describe a model of computation which has been defined and proved to be a universal Chaitin machine U. We then propose a method (procedure) which combines iterative executions of an algorithm with mathematical analysis to get the exact values of the first successive 64 bits of the corresponding Chaitin ΩU number of U. This particular defined Chaitin machine U is essentially a register machine and has been implemented in Java. We call it the canonical compressed model (or compressed model) as it allows only ‘canonical’ program strings to be processed in U. Thus, many input strings which are illegal, hence useless, are ignored and never involved in the computational process. In addition, the compressed design shortens the length of all instructions so that relatively short strings now contain somewhat complex programs. A simulator for U, written in Java, is a primary part of the project. The algorithm is executed iteratively, computing step by step an increasing sequence of rational numbers (in binary) to approximate Ω U. In the n-th step, the algorithm produces four main output files: all halting strings, looping strings, run-time errors, and prefix strings (incomplete programs). In each step, all prefix strings (of the previous step) are read and processed one by one. Each string is extended by 7 bits (ASCII code representations for symbols) to generate new strings that are examined one by one to detect any lexical, syntactic, semantic, or run-time error in each of them. Any of those strings with an error detected is discarded to save storage space and execution time. We solve the Halting Problem for all programs for U of length less than or equal to 84 bits so we can calculate an increasing sequence of exact approximations converging to ΩU. By means of a mathematical analysis the first successive 64 bits, 0000001000000100000110001000011010001111110010111011101000010000 of the 84 bits are proved to be the exact first bits of ΩU. Actually, more bits can be obtained by this procedure if the disk space is sufficient for it to go on, but this procedure cannot be extended indefinitely. In order to assure that our computing result is correct, we have proved that all input strings of length less than or equal to 84 executed in U over 100 steps are not halting programs.* *This dissertation is a compound document (contains both a paper copy and a CD as part of the dissertation). The CD requires the following system requirements: Adobe Acrobat; Microsoft Office.
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Siliņš, Ilvars. "Molecular epidemiology of human papillomavirus and cervical cancer /." Stockholm : [Karolinska institutets bibl.], 2001. http://diss.kib.ki.se/2001/91-7349-091-1/.

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Duan, Jianxin. "Protein folding, stability and recognition /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7140-098-2/.

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Hermansson, Liselotte. "Upper limb reduction deficiencies in Swedish children : classification, prevalence and function with myoelectric prostheses /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7140-091-5/.

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Stubbs, Estelle Vivien. "A study of the codicology of four early manuscripts of the Canterbury Tales." Thesis, University of Sheffield, 2006. http://etheses.whiterose.ac.uk/15177/.

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This thesis is a study of the physical features of the four earliest manuscripts of the Canterbury Tales all dated to the first years after the death of Geoffrey Chaucer. I assess the ways in which codicological examination can contribute to the understanding of a complex textual tradition and inform the study of the text. The thesis is divided into two volumes. The first volume contains the seven chapters which make up the thesis. The first chapter contains a review of the printed editions of the poem since Caxton's first edition of 1476 and a summary of the most important contributions of scholarship in the twentieth century. It reveals that many influential editions and much scholarship on the textual tradition of the poem have been achieved with scant consultation of the extant manuscripts. The second chapter addresses the problems which have arisen as a result of this neglect and offers suggestions for a different approach to manuscript analysis which will be provided as a result of the examination of the manuscripts in the remainder of the thesis. Chapters three to six contain detailed analyses of the four manuscripts in the survey: Aberystwyth, National Library of Wales MS. Peniarth 392D (Hengwrt), Oxford, Corpus Christi College, MS. 198 (Corpus), London, British Library MS. Harley 7334 (Harley 4), and California, San Marino, Huntington Library MS. El. 26 C 9 (Ellesmere). In chapter seven, I summarise the findings and offer suggestions for future research. The second volume contains all the appendices numbered 1-20 followed by 22 Plates. For each manuscript there are four or five separate appendices which provide details of the following: a visual overview, a detailed analysis of individual quires, a list of all rubrics, lines added, omitted or variant in each manuscript, and a list of catchwords.
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Himsworth, Katherine. "The Peniarth MS 22 Brut y Brenhinedd and continuation chronicle, and its 15th century Aberystwyth scribe, Dafydd ap Maredudd Glais." Thesis, Aberystwyth University, 2015. http://hdl.handle.net/2160/5dcc8e8b-3f1d-4a4d-9713-d9ed9c7288f1.

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The Peniarth 22 manuscript is, except for the last four pages, a fifteenth-century copy of Brut y Brenhinedd, the Welsh translation of Geoffrey of Monmouth's Historia Regum Britanniae; it was penned in 1444 by one Dafydd ap Maredudd Glais. It belongs to the Dingestow family of manuscripts, which in turn is related, in part, to the Llanstephan Version and Liber Coronacionis Britanorum manuscripts, although the detail of this relationship - and that of the Dingestow manuscripts to one another - still begs a number of questions. Peniarth 22 itself is very similar to, though not a copy of, the early fourteenth-century NLW 3036B manuscript. But there are differences in the orthography, and to a lesser extent in the grammatical constructions used by Dafydd which shed light on the changes that were being gradually adopted in the fifteenth century. This is particularly true of the last four pages, which contain Dafydd's own translation of a Latin chronicle, which comprises a continuation of the Brut. While incomplete, largely formulaic and in parts illegible, it includes detail of historical as well as linguistic interest. Dafydd himself, far from being an institutional scribe, led a colourful life including both murder and public service in fifteenth-century Aberystwyth. But he was not, as previously thought, a cleric.
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Wang, Jianlan. "Silk facing of ancient Chinese manuscripts." Thesis, Queen's University Belfast, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.675481.

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The thesis has profiled silk facing treatments to manuscripts in the Stein Collection in the British Library, via its unique historical background, compared with the lamination technique that was prevalent in conservation in the last century in libraries and archives. The correction of the previous inappropriate preservation methods might have not aroused enough attentiveness, or critical attention, in the conservation arena. IR and Raman spectroscopy were widely applied in this project, for the characterisation of the different silks removed from the manuscripts, in comparison with new silk from commercial suppliers, revealing the ageing of silk, its fragility and stiffness, which causes mechanical abrasion toward the scrolls of ancient manuscripts. Silk's absorption of moisture, and exposure to light, exacerbate this problem. The characterisation of a series of vegetable and animal derived glues emphasises the poor record-keeping of the conservation studios. The non-native and pipeline-processed starches show almost the same pattern in both IR and Raman spectroscopy. Animal glues also show different patterns from the starch-based glues in both IR and Raman spectroscopy. The problems of applying gelatine-base glue in the conservation process are also discussed. The dye-transfer phenomenon has been confirmed: the yellow dye from the manuscripts (which were dyed by water-soluble huangbo extracts) transfer to the glue paste and then to the silk materials, thus causing the discolouration of the manuscripts. Finally, solid-state NMR characterisation with magic angle spinning was used to characterise the silks and glue pastes. The SEM and EDAX study provided the evidence for the existence of fungi and/or bacteria on the glues al1ached to the manuscripts, data being provided from a strong collaboration with Dr. Cristina Silva Pereira from the Universidade Nova de Lisboa, Portugal. Preliminary studies have confirmed that the silk and glue carry Aspergillus niger, Neurospora crass a and Penicillium chrysogenum. This observation provides unimpeachable evidence that long-term damage will occur to the faced manuscripts if the facing is not removed. Currently, the desire for digitisation of manuscripts in the Stein collection in the British Library also enhances the case for the removal of the silk facing materials. The sill<, glue, water and dye, compose a complicated matrix which influence the lifetime and stability of the manuscripts by interaction with the external environment, thus it is believed that the removal the silk facing materials is reasonable, and should be performed if economically viable
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Beattie, Luke Timothy. "How were the anonymous Castle Ashby play manuscripts created, and why?" Thesis, University of Exeter, 2011. http://hdl.handle.net/10036/3478.

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In 1977, a long-lost collection of manuscripts of plays, poems, and non-fiction texts from the 17th century was re-discovered in the library of Castle Ashby, Northamptonshire. Most of the items are not signed by an author, and have no known record of publication or performance. These technically anonymous items have received minimal scholarly attention in the three-plus decades since their recovery, and what comment there has been has not entirely agreed upon the collection's authorship, purpose, or even era of composition. This thesis takes a confident position on those debates by investigating the unsigned manuscripts and their contents through a variety of techniques. This study reviews the collection's known history, past commentators' findings and conclusions, and the physical and textual properties, and comes to an authorial conclusion based on a fresh palaeographic investigation; it then offers a biography of the proposed writer. It statistically analyses the collection's material, palaeographic, and metrical traits, in search of trends that might show a development over time. It applies modern electronic resources to investigate the collection's textual interrelationships and plausible literary sources, and uses contemporary history and the proposed author's biography to suggest conjectural allusions in the writing. Together, those avenues of analysis allow for a best-guess ordering and dating to be proposed for the collection's contents. Turning specifically to the dramatic texts, the thesis then considers the proposed author's potential theatrical resources, searches the manuscripts for evidence of possible professional theatrical use, and gathers dramaturgical information from the texts themselves to form an opinion about how plausible contemporary performances would have been; this is supplemented with the findings from the first modern stagings of all of the dramatic texts, which establish what minimum physical needs the plays would demand in performance, and identify where there are dramaturgical issues that could limit the plays' theatrical practicality. The study's findings up to that point then allow for the collection to be positioned within their period's larger context of authorial and theatrical activity, conclude whether the writer achieved anything unique, and, identifying the collection's major recurring thematic elements, propose a rationale for the writer's authorial activity. In summary, this thesis sets out to determine the conditions that brought the unsigned Castle Ashby texts into existence, and to suggest why they were written at all.
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White, Thomas. "Potential lives : the matter of late medieval manuscripts." Thesis, Birkbeck (University of London), 2016. http://bbktheses.da.ulcc.ac.uk/222/.

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Late medieval vernacular literary texts frequently reflect on their physical existence; they establish a poetics of material composition that is productively ambivalent about the contingencies of literary making in a manuscript culture. This thesis traces the ‘potential life’ of a late medieval manuscript. Four keywords (blankness, palimpsests, textiles, and fragments) provide the impetus for a discussion that connects a wide range of literary, codicological, and theoretical materials, in a mode that is iterative and additive. Manuscripts are not simply containers or substrates for literary texts; varied and ambivalent ideas about manuscripts are deeply embedded in the medieval period’s cultural and philosophical moment: they are the ‘matter’ of medieval writing in the dual sense of that word. In exploring the theoretical, figurative, and interpretative possibilities of manuscript study this thesis turns to a wide range of late medieval texts: these include the works of Geoffrey Chaucer, vernacular romance, The Book of Margery Kempe, The Book of Sir John Mandeville, and Thomas Hoccleve’s Series. The numerous and varied manuscripts of The Book of Sir John Mandeville form a central focus. As well as engaging with the late medieval period’s own rich vocabulary for describing the transformations of matter, I use contemporary ecological theory and new materialism in order to think further about the materials of medieval books. The work of Michel Serres, Bruno Latour, Tim Ingold, and Jonathan Gil Harris provides the occasion not simply to ‘apply’ contemporary theory to medieval materials, but to trace a more dialectical history in which theoretical, literary, and manuscript materials are brought into productive contact. This thesis demonstrates that late medieval manuscripts are sites where multiple temporalities are interwoven, in a manner that should encourage a critical self-­‐‑reflexiveness about how scholars narrate the lives of manuscripts, as well as about the modern archiving procedures that have come to condition our access to the medieval past. It reflects critically on the ways in which the medieval textual record has come to be fragmented, archived, and disciplined in the postmedieval period.
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Buggins, Rosemary Elisabeth. "The Coventry pontifical and liturgical transmission patters in the twelth and thirteenth centuries." Thesis, University of Bristol, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.682347.

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The focal point of this thesis is my complete transcription of the thirteenth-century Coventry Pontifical manuscript (Cambridge, University Library, Ff. VI. 9). In order to contextualise the Coventry Pontifical manuscript, this thesis comprises two investigative strands. The first is an exploration of the significance of the manuscript in the lives of its medieval users; the interactions between the manuscript and its culture; and the interplay between the manuscript and its users. To further our understanding of the significance of the Coventry Pontifical to its users, this thesis surveys the liturgical practices included in the manuscript, and how these practices and the production of the manuscript required the skills and money of the general population as well as the monastic community. An examination of routines of the time and an overview of the politics and people connected to the Diocese of Coventry and Lichfield follows. Contemplating the people who used the manuscript and how they used it leads to appreciation of the manuscript, and my transcription of it, beyond the significance to the user. It increases awareness of how and why the manuscript was compiled. The second strand uses the Coventry manuscript as a focus for a broader exploration of textual and musical liturgical transmission patterns of insular pontifical manuscripts in the twelfth and thirteenth centuries. Tracing these patterns of transmission, using a combination of variant categorisation and statistical analysis, reveals any relationships which exist between manuscripts produced across medieval Britain. The analysis, combined with consideration of the nature of pontifical exemplars, allows me to explore how pontifical transmission differs from that of other types of liturgical manuscript. This investigation of transmission patterns pinpoints the relative position of the Coventry manuscript in its insular liturgical setting, and thus emphasises the significance of my complete transcription of the manuscript to current scholarship.
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Hirschfeld, Marin. "Intimacy in contemporary digital cinema." Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:8e212865-09d1-4bf7-bf05-76806a2e1e21.

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Critical discourses on contemporary digital cinema tend to be either overtly negative, framed within a rhetoric of loss or disenfranchisement, or unilaterally positive, celebrating the user agency and freedom digital technologies enable. Both these conceptual positions are unhelpful because they either focus on what contemporary digital cinema fails to do or what it should do, without examining more closely how it actually functions. What is needed is a third, neutral approach which takes both sides into consideration but is also aware of their limitations and weaknesses. This thesis takes as its impetus Giles Deleuze’s suggestion that, just like the cinemas of the movement-image and the time-image before it, contemporary digital cinema needs a basic will to art – a new aesthetic principle, a new function of the image, a new politics, a new representational potential distinct from those that have come before it. The aim of this thesis is therefore to establish this will to art and explore its ramifications for and manifestations in contemporary digital cinema. Taking into consideration a variety of filmic texts from the 1980s to the present day which prominently feature diegetically recorded footage, as well as amateur film-making practices from the home movies of the 1960s to the video clips now uploaded to online media sharing platforms, the increasing relevance of home media in the reception of contemporary digital cinema, and most crucially the process of convergence inherent in digital media, this thesis argues that the will to art of contemporary digital cinema is intimacy.
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37

Swenson, Sarah A. "A gene's eye vew : W.D. Hamilton, the science of society, and the new biology of enlightened self-interest, 1950-1990." Thesis, University of Oxford, 2015. http://ora.ox.ac.uk/objects/uuid:4c979713-0911-4cc0-9a7f-05fb0455f128.

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W.D. Hamilton has been celebrated as the twentieth-century Darwin. His extension of evolutionary theory to explain social behaviours has been extensively documented. Current accounts, however, have often overlooked the extent to which his early research goals were tied to his desire to see that a better world was created through a scientific understanding of society. In fact, when his interests in humans, and especially his eugenic concerns, have been acknowledged, they have been distanced from his scientific achievements and treated separately. Using new sources to reexamine the development of Hamilton’s most famous idea, the theory of inclusive fitness, we may better understand how his perception of cultural upheaval shaped his reading of social behaviours as evolved characters following universal laws. Understanding this, we may see that however successful Hamilton was, he never realized his original dream, which was to devise a theory that would inform the human world, replacing religious and ideological beliefs. As he sought to solidify his career in the 1970s, he moved away from publicly disclosing his more controversial ideas. This meant that by the time the science of social behaviour inspired heated debates, he was almost always absolved from political critiques. Many assumed that his theory was derived from observations of insects, and his eugenic ideas were forgotten, ignored, or not understood. He was therefore well positioned to become the objective figurehead of a new discipline, sociobiology. This does not mean that his desire to understand society as the result of genetic laws subsided, and by placing inclusive fitness against its social and political background, we might reimagine its trajectory and its impact in new ways. We might also begin to see Hamilton not as an isolated scholar unengaged with society but as an individualist whose extra-scientific beliefs paralleled his scientific theories in meaningful ways.
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38

Florence, Margaret Mary. "Migration Stimulating Factor : the search for inhibitors." Thesis, University of Dundee, 2013. https://discovery.dundee.ac.uk/en/studentTheses/20738022-0982-4ec5-ade3-3cdf8e5beed3.

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The oncofetal protein Migration Stimulating Factor (MSF) is a truncated isoform of human fibronectin which exhibits numerous bioactivities that are pertinent to cancer progression. The MSF protein (70kDa) has potent motogenic activity, with only femtomolar concentrations required to produce half-maximal. The proteolytic degradation of MSF generates the functionally equivalent 43kDa Gel-BD domain and 21kDa IGD peptide. The screening of conditioned medium (CM) for bioactivity revealed two sources of MSF-inhibitory (MSF-I) activity; the spontaneously immortalised human keratinocyte cell line (HaCaT) and endothelial cells (ENDO 742) specifically when exhibiting a cobblestone phenotype. The CM from the HaCaT keratinocyte line was fractionated by both molecular weight and ionic charge, followed by sequence analysis which identified the inhibitor as Neutrophil Gelatinase Associated Lipocalin (NGAL). Both recombinant and cell-produced NGAL neutralise the motogenic activity of MSF. This novel bioactivity for NGAL is not dependent on its iron transportation capability or direct binding to MSF. HaCaT cells also secrete MSF; the bioactivity of which is masked by the co-expression of NGAL. The relative expression levels of the pro- and anti-motogenic factors, MSF and NGAL, were assessed using an in vitro model for human skin carcinogenesis, the HaCaT –ras clones. The shift in tumorigenic potential from benign to metastatic was characterised by a decrease in NGAL and an increase in MSF expression, indicating their potential role in tumour progression. The protein responsible for the MSF inhibitory activity is cell- type specific; NGAL is not expressed by endothelial cells in vitro. MSF stimulates the generation of sprouting endothelial cells from a cobblestone monolayer and acts a survival factor for spontaneously sprouting cells within a 3D matrix. NGAL does not selectively the target sprouting phenotype of endothelial cells, but induces apoptosis in all endothelial cells. Fractionation of endothelial CM revealed that both sprouting and cobblestone cells express bioactive MSF and a MSF-I. Endothelial MSF-I was located in fractions of MW 70kDa, 40kDa and =25kDa; further investigation is required to identify the protein responsible.
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39

Lee, Elaine Carole. "Disclosure in maternity care contexts : the paradigm case of sexual orientation." Thesis, University of Dundee, 2010. https://discovery.dundee.ac.uk/en/studentTheses/f6167a54-09d1-4e3e-a31d-e2108dca9fce.

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This thesis is a hermeneutic phenomenological study of the concept of disclosure in maternity care contexts using the example of sexual orientation. There is a significant body of literature within psychology and sociology relating to the health and social purposes and consequences of disclosure. There is a further body of outcomes-focused evidence relating to disclosure of sexual orientation in health care. There is, however, little research undertaken into the disclosure of sexual orientation in pregnancy as an action with motive and purpose. This study aimed to address this issue. The study employed unstructured interviews with eight lesbian mothers, seven of whom were birth mothers and one was a social mother. The hermeneutic method used an iterative process of analysis integrating researcher pre-understandings, thematic analysis of individual interview transcripts and broader analysis of the individual interview data within the total interview data, exploring the parts within the whole. The aim was to identify the shared meaning of disclosure for the participants Data analysis resulted in five main themes: being invisible/visible; being upfront; being me; being entitled; being safe. An additional finding was the process of managing negativity through strategies such as rationalisation. Three encompassing concepts were identified: protection; power; and identity. Two motivations for disclosure were also identified: pro-action and altruism The thesis concludes that disclosure is a motivated and purposeful act which has real meaning and consequences. It makes extensive recommendations for midwifery practice including acknowledging the disclosure, understanding the legal complexity, and recognising the lesbian family. Recommendations for policy suggest having explicit and detailed policies that include information about how to be inclusive rather than only abstract concepts of inclusion. Recommendations for research include qualitative and quantitative research with midwives about attitudes and knowledge as well as research exploring the role of the social mother in promoting family health outcomes.
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40

Ankit, Bajpai. "SQL versus MongoDB from an application development point of view." Kansas State University, 2014. http://hdl.handle.net/2097/18816.

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Master of Science
Department of Computing and Information Sciences
Doina Caragea
There are many formats in which digital information is stored in order to share and re-use it by different applications. The web can hardly be called old and already there is huge research going on to come up with better formats and strategies to share information. Ten years ago formats such as XML, CSV were the primary data interchange formats. And these formats were huge improvements over SGML (Standard Generalized Markup Language). It’s no secret that in last few years there has been a huge transformation in the world of data interchange. More lightweight, bandwidth-non-intensive JSON has taken over traditional formats such as XML and CSV. BigData is the next big thing in computer sciences and JSON has emerged as a key player in BigData database technologies. JSON is the preferred format for web-centric, “NoSQL” databases. These databases are intended to accommodate massive scalability and designed to store data which does not follow any columnar or relational model. Almost all modern programming languages support object oriented concepts, and most of the entity modeling is done in the form of objects. JSON stands for Java Script object notation and as the name suggests this object oriented nature helps modeling entities very naturally. And hence the exchange of data between the application logic and database is seamless. The aim of this report is to develop two similar applications, one with traditional SQL as the backend, and the other with a JSON supporting MongoDB. I am going to build real life functionalities and test the performance of various queries. I will also discuss other aspects of databases such as building a Full Text Index (FTI) and search optimization. Finally I will plot graphs to study the trend in execution time of insertion, deletion, joins and co- relational queries with and without indexes for SQL database, and compare them with the execution trend of MongoDB queries.
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41

Vidiyala, Akhila. "Android application of Throck mobile." Kansas State University, 2013. http://hdl.handle.net/2097/15318.

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Master of Science
Department of Computing and Information Sciences
Daniel Andresen
The aim of this project is to develop an android application for managing and organizing activities of various departments in ThrockMorton building at K-State. Mobile application development is a growing trend in computer industry. With the advancements in mobile technologies and efficient 3G and 4G wireless communications, a number of desktop applications are now becoming available as mobile applications. Android has the leading market share in the entire smart phone OS available. It gives lot of space for creative development as it is open source. There are various discussion forums and official android development support websites that encourage mobile and tablet application development. The ThrockMobile application provides many features for managing inventory at ThrockMorton in Kansas State University. The features include scanning a barcode of an asset and displaying its details and can even edit any of the fields if needed. The access to this application is restricted to only those devices whose device id is existing in the database. One can request access to the application through an email client integrated with the application. Look up feature lets you look up for a user, room, ip-address and asset. Preferences module lets you enter the details of the server from which data is to be requested. This application has been tested on android devices of varying screen sizes and android OS versions. The application serves requests at an average rate of 1.5sec/request, which is above the industry average time. I mentioned in detail the reason for the above performance average times and as future enhancements I have discussed the possible solutions.
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42

Sanderson, Robert. "Linking past and future : an application of dynamic HTML for medieval manuscript editions." Thesis, University of Liverpool, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.288863.

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43

McCrae, James. "Sketch-based Path Design." Thesis, 2008. http://hdl.handle.net/1807/11154.

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We first present a novel approach to sketching 2D curves with minimally varying curvature as piecewise clothoids. A stable and efficient algorithm fits a sketched piecewise linear curve using a number of clothoid segments with G2 continuity based on a specified error tolerance. We then present a system for conceptually sketching 3D layouts for road and other path networks. Our system makes four key contributions. First, we generate paths with piecewise linear curvature by fitting 2D clothoid curves to strokes sketched on a terrain. Second, the height of paths above the terrain is automatically determined using a new constraint optimization formulation of the occlusion relationships between sketched strokes. Third, we present the break-out lens, a novel widget inspired by break-out views used in engineering visualization, to facilitate the in-context and interactive manipulation of paths from alternate view points. Finally, our path construction is terrain sensitive.
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44

Benabbas, Siavosh. "On Hierarchies of Strong SDP Relaxations for Combinatorial Optimization Problems." Thesis, 2012. http://hdl.handle.net/1807/33933.

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Studying the approximation threshold of NP-hard optimization problems, i.e. the ratio of the objective value achievable by a polynomial time algorithm to that of the optimal solution is an important field in theoretical computer science. In the past two decades there has been significant development both in terms of finding good approximation algorithms, e.g. through the use of semidefinite programming and hardness of approximation, e.g. the development of Probabilistically Checkable Proofs and Unique Games Conjecture. Trying to prove lower bounds for the approximation threshold of an optimization problem, one could take one of two approaches. In the first approach, one proves such lower bounds under a complexity assumption like P =/= NP or Unique Games Conjecture. In the second approach, one studies the behaviour of prominent algorithmic schemes, such as Linear Programming (LP) and Semidefinite Programming (SDP) relaxations for the problem of interest. There, the measure of efficiency is the integrality gap which sets the approximation limitation of the algorithms based on these relaxations. In this work we study the integrality gap of families of strong LP and SDP relaxations for a number of combinatorial optimization problems. The relaxations come from the context of Lift-and-Project systems. There one starts from a standard (weak) relaxation from a problem and iteratively adds more constraints to make the relaxation stronger, i.e. closer to an exact formulation of the problem. We mostly study the performance of the Sherali-Adams SDP relaxations. Specifically, the main contributions of this thesis are as follows. • We show optimal integrality gaps for the level-\Theta(n) Sherali-Adams SDP relaxation of MAX k-CSP_q(P) for any predicate P:[q]^k -> {0,1} satisfying a technical condition, which we call being promising. Our result show that for such predicates MAX k-CSP_q (P) cannot be approximated (beyond a trivial approximation) by the Sherali-Adams SDP relaxations of even very high level. Austrin and Håstad (SIAM J. Comput., 2011) show that a random predicate is almost surely promising. • We complement the above result by showing that for some class of predicates which are not promising MAX k-CSP_q(P) can be approximated (beyond the trivial approximation) by its canonical SDP relaxation. • We show optimal integrality gap lower bounds for level-poly(n) Sherali-Adams SDP relaxations of Quadratic Programming. We also present superconstant integrality gap lower bounds for superconstant levels of the same hierarchy for MaxCutGain. • We show optimal integrality gap lower bounds for the level-5 Sherali-Adams SDP relaxation of Vertex Cover. We also conjecture a positivity condition on the Taylor expansion of a certain function which, if proved, shows optimal integrality gaps for any constant level of the Sherali-Adams SDP hierarchy for Vertex Cover. • We revisit the connection between integrality gap lower bounds and the Frankl-Rödl theorem (Trans. of the AMS, 1987). We prove a new density version of that theorem which can be interpreted as a new isoperimetric inequality of the Hamming cube. Using this inequality we prove integrality gap lower bounds for the Lovász-Schrijver SDP (resp. Sherali-Adams LP) relaxation of Vertex Cover (resp. Independent Set) in degree bounded graphs.
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45

Trommelen, Michelle Suzanne. "Quaternary stratigraphy and glacial history of the Fort Nelson (southeast) and Fontas River (southwest) map areas (NTS 094J/SE and 0941/SW), northeastern British Columbia." Thesis, 2006. http://hdl.handle.net/1828/2009.

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The study area in northeast British Columbia extends from the Rocky Mountains in the west to the Fort Nelson Lowland in the east, and includes the westernmost extend of the Laurentide Ice Sheet (LIS) and the easternmost extend of the Cordilleran Ice Sheet (CIS) in the Late Pleistocene. Surficial mapping conducted over portions of the Fontas and Fort Nelson map areas (NTS 094I/SW and 094J/SE, respectively) provides information on sediment distribution and characteristics as well as glacial history. This information has direct implications for geotechnical investigations, aggregate resources and diamond exploration in the region. Non-glacial pre-Late Wisconsinan sediments occur at multiple sites along the Prophet River, providing a pre-glacial or interglacial history for the area. Geochemical analysis and clast lithologies were used to differentiate between sediments derived from the LIS to the east, and Montane/CIS glaciers to the west. The Quaternary stratigraphy of the Prophet River valley indicates the presence of a paleo-Prophet River valley system. Nonglacial deposits in the paleovalley include overbank fines and floodplain sediments interbedded with fluvial gravels. Macrofossils within horizontally laminated organic-rich black clay and silt are interpreted to indicate deposition in the floodplain of the paleo-Prophet River within oxbow-lakes and possibly also sag ponds. The climate is interpreted to be similar to present within a dominantly spruce forest. Wood found at one site provided a radiocarbon date of 49 300±2000 BP, while wood obtained from five other sites provided non-finite radiocarbon ages. In the Late Wisconsinan, the LIS advanced west-southwest into the study area, blocking existing east-flowing regional drainage, and forming an ice-dammed proglacial lake in the Prophet River valley. Ice overrode these sediments and deposited clast-poor clayey-silt till over the entire region. Thicknesses range from less than one metre to greater than twenty metres in the Prophet River valley. In river-cut sections near the Rocky Mountains in the Fort Nelson and Tuchodi Lakes map areas, potassium-feldspar rich granitoid and gneissic clasts, derived from the Canadian Shield, are generally found only east of the foothills, except along the Tetsa River valley. Near the mountain front, in Tuchodi River valley, outwash from Montane/Cordilleran glacial meltwaters was deposited before the LIS advanced and ponded the valley in the Late Wisconsinan. The geochemistry of 303 till samples collected throughout the study area is used to evaluate the regional glacial history inferred from stratigraphic and geomorphic data. Three different geochemical populations are recognized and corroborated by clast lithology (relative percent) from 56 till and glaciofluvial samples. One population, covering the northeast portion of the study area, was likely deposited by the LIS where it extended west into the Rocky Mountain front during the Late Wisconsinan. The second population suggests that the eastern extent of Montane/Cordilleran ice during the Late Wisconsinan was at least to the Rocky Mountain Foothills; however its easternmost position remains unknown. The third population can be attributed to Late Wisconsinan LIS reworking sediment deposited on the Interior Plains by the CIS, either in the Late Wisconsinan or earlier. During early deglaciation, the ice retreated to the east-northeast, impounding local drainage at the ice margin, forming Glacial Lake Prophet in the Fort Nelson map area and Glacial Lake Hay in the Fontas map area. Glacial lakes followed the retreating ice margin and drained through a variety of meltwater channels. The exposed glacial lacustrine plain became a source for sand dunes oriented southeast indicating katabatic paleowinds from the northwest (NTS 094I/SE).
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46

Meeds, Edward. "Nonparametric Bayesian Methods for Extracting Structure from Data." Thesis, 2008. http://hdl.handle.net/1807/11235.

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One desirable property of machine learning algorithms is the ability to balance the number of parameters in a model in accordance with the amount of available data. Incorporating nonparametric Bayesian priors into models is one approach of automatically adjusting model capacity to the amount of available data: with small datasets, models are less complex (require storing fewer parameters in memory), whereas with larger datasets, models are implicitly more complex (require storing more parameters in memory). Thus, nonparametric Bayesian priors satisfy frequentist intuitions about model complexity within a fully Bayesian framework. This thesis presents several novel machine learning models and applications that use nonparametric Bayesian priors. We introduce two novel models that use flat, Dirichlet process priors. The first is an infinite mixture of experts model, which builds a fully generative, joint density model of the input and output space. The second is a Bayesian biclustering model, which simultaneously organizes a data matrix into block-constant biclusters. The model capable of efficiently processing very large, sparse matrices, enabling cluster analysis on incomplete data matrices. We introduce binary matrix factorization, a novel matrix factorization model that, in contrast to classic factorization methods, such as singular value decomposition, decomposes a matrix using latent binary matrices. We describe two nonparametric Bayesian priors over tree structures. The first is an infinitely exchangeable generalization of the nested Chinese restaurant process that generates data-vectors at a single node in the tree. The second is a novel, finitely exchangeable prior generates trees by first partitioning data indices into groups and then by randomly assigning groups to a tree. We present two applications of the tree priors: the first automatically learns probabilistic stick-figure models of motion-capture data that recover plausible structure and are robust to missing marker data. The second learns hierarchical allocation models based on the latent Dirichlet allocation topic model for document corpora, where nodes in a topic-tree are latent ``super-topics", and nodes in a document-tree are latent categories. The thesis concludes with a summary of contributions, a discussion of the models and their limitations, and a brief outline of potential future research directions.
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47

Medvedev, Paul. "Genome Graphs." Thesis, 2010. http://hdl.handle.net/1807/26297.

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Whole-genome shotgun sequencing is an experimental technique used for obtaining information about a genome’s sequence, whereby it is broken up into many short (possibly overlapping) segments whose sequence is then determined. A long-standing use of sequencing is in genome assembly – the problem of determining the sequence of an unknown genome, which plays a central role for the sequencing of novel species. However, even within the same species, the genomes of two individuals differ, and though these variations are relatively small, they account for the observed variation in phenotypes. A large portion of these are copy number variants (CNVs), or genomic segments which appear a different number of times in different individuals. The unifying theme of this thesis is the use of genome graphs for both CNV detection and genome assembly problems. Genome graphs, which have already been successfully used for alignment and assembly, capture the structure of a genome even when its sequence is not fully known, as with the case of sequencing data. In this thesis, we extend their uses in several ways, culminating in a method for CNV detection that is based on a novel genome graph model. First, we demonstrate how the double-stranded nature of DNA can be efficiently incorporated into genome graphs by using the technique of bidirected network flow. Furthermore, we show how genome graphs can be efficiently used for finding solutions that maximize the likelihood of the data, as opposed to the usual maximum parsimony approach. Finally, we show how genome graphs can be useful for CNV detection through a novel construction called the donor graph. These extensions are combined into a method for detecting CNVs, which we use on a Yoruban human individual, showing a high degree of accuracy and improvement over previous methods.
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48

Kvasov, Stanislav. "DREM: Architectural Support for Deterministic Redundant Execution of Multithreaded Programs." Thesis, 2009. http://hdl.handle.net/1807/18795.

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Recently there have been several proposals to use redundant execution of diverse replicas to defend against attempts to exploit memory corruption vulnerabilities. However, redundant execution relies on the premise that the replicas behave deterministically, so that if inputs are replicated to both replicas, any divergences in their outputs can only be the result of an attack. Unfortunately, this assumption does not hold for multithreaded programs, which are becoming increasingly prevalent -- the non-deterministic interleaving of threads can also cause divergences in the replicas. This thesis presents a method to eliminate concurrency related non-determinism between replicas. We introduce changes to the existing cache coherence hardware used in multicores to support deterministic redundant execution. We demonstrate that our solution requires moderate hardware changes and shows modest overhead in scientific applications.
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49

Daniella, Perri. "The Role of Intravenous Immunoglobulin Anti-A and Anti-B in Complement Activation and Red Blood Cell Phagocytosis." Thesis, 2009. http://hdl.handle.net/1807/18976.

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Intravenous immunoglobulin is a human blood derived product that is used to treat immunodeficiencies and autoimmune disorders. An adverse side effect of IVIg therapy is hemolysis. Patients who experience hemolysis are mainly blood group A or AB. Clinical laboratory studies have demonstrated that IVIg contains ABO blood group antibodies, which can bind complement proteins. This study hypothesizes that anti-A/B in IVIg will bind to A/B antigens and activate complement in a dose dependant manner, which may lead to enhanced RBC phagocytosis. This study observed that the quantity of ABO antigens does not affect the in vitro binding of IVIg to RBCs. IVIg induced C3b deposition at high doses; however, the amount of complement deposition was insufficient to enhance phagocytosis of IVIg-sensitized RBCs by monocytic THP-1 cells in vitro. These studies emphasize that hemolytic reactions involve many factors in conjunction with antibodies and complement proteins.
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50

Filmus, Yuval. "Spectral Methods in Extremal Combinatorics." Thesis, 2013. http://hdl.handle.net/1807/43555.

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Extremal combinatorics studies how large a collection of objects can be if it satisfies a given set of restrictions. Inspired by a classical theorem due to Erdos, Ko and Rado, Simonovits and Sos posed the following problem: determine how large a collection of graphs on the vertex set {1,...,n} can be, if the intersection of any two of them contains a triangle. They conjectured that the largest possible collection, containing 1/8 of all graphs, consists of all graphs containing a fixed triangle (a triangle-star). The first major contribution of this thesis is a confirmation of this conjecture. We prove the Simonovits–Sos conjecture in the following strong form: the only triangle-intersecting families of measure at least 1/8 are triangle-stars (uniqueness), and every triangle-intersecting family of measure 1/8−e is O(e)-close to a triangle-star (stability). In order to prove the stability part of our theorem, we utilize a structure theorem for Boolean functions on {0,1}^m whose Fourier expansion is concentrated on the first t+1 levels, due to Kindler and Safra. The second major contribution of this thesis consists of two analogs of this theorem for Boolean functions on S_m whose Fourier expansion is concentrated on the first two levels. In the same way that the Kindler–Safra theorem is useful for studying triangle-intersecting families, our structure theorems are useful for studying intersecting families of permutations, which are families in which any two permutations agree on the image of at least one point. Using one of our theorems, we give a simple proof of the following result of Ellis, Friedgut and Pilpel: an intersecting family of permutations on S_m of size (1−e)(m−1)! is O(e)-close to a double coset, a family which consists of all permutations sending some point i to some point j.
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