Thesis (M.A.)--University of Wisconsin--Madison. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 193-201).

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Thesis (Ph.D.)--Boston University / PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / The mechanisms by which diets high in saturated fat (HFD) contribute to intestinal adaptation and obesity are unknown. The hypothesis that functional changes in distal portions of small intestine are induced by HFD was tested in C57B1/6 mice. Specifically, it was examined whether the putative fatty acid translocase CD36 was phosphorylated in mouse intestinal epithelial cells and whether dephosphorylation of CD36 increased long chain fatty acid (LCFA) absorption. Co-immunoprecipitation was used to investigate specific intestinal alkaline phosphatases that might interact with CD36. It was also examined whether chronic ingestion of an HFD would lead to upregulation of the CD36 and/or one or more intestinal alkaline phosphatases that may activate CD36. CD36 was found to be phosphorylated on the surface of mouse enterocytes, indicating that there may be a phosphatase-sensitive pool of phospho-CD36 (pCD36) in mouse small intestinal tissue. CD36 was dephosphorylated by alkaline phosphatase and this treatment increased long chain but not short chain fatty acid uptake. Long chain fatty acid uptake was blocked with a specific CD36 inhibitor. CD36 from mouse small intestines physically interacted specifically with global intestinal alkaline phosphatase (gIAP) but not duodenal alkaline phosphatase (dIAP). As expected, HFD increased body weight, adiposity, and plasma triglycerides compared to control mice. CD36 and gIAP but not dIAP protein levels were significantly increased in distal but not proximal regions of intestines of HFD mice. Finally, HFD increased the absorptive capacity of the distal small intestine for LCFA in a CD36-dependent manner. It is concluded that HFD specifically upregulates gIAP protein in epithelial cells of the distal regions of the small intestine of mice, and that one of its substrates is pCD36, which has been implicated in transcellular fat transport. This diet also increases the absorptive capacity of the distal small intestine for LCFAs. Taken together, these results suggest that HFD causes intestinal adaptation that results in an increased capacity to absorb dietary fat. This effect is mediated in part by increasing the expression and activity of the fatty acid transporter CD36 and its regulatory enzyme gIAP. / 2031-01-02

Recent years have seen an expansion beyond the more druggable biological targets into novel areas of biological space. However, drug discovery campaigns against these challenging targets have been afflicted with low hit rates during screening campaigns and high levels of candidate attrition during clinical trials. Subsequent studies have looked to explore the underlying factors to these challenges and have identified the lack of scaffold diversity and poor physicochemical properties in screening libraries as the leading causes. In an attempt to address this issue drug discovery strategies such as fragment-based drug discovery and lead-oriented synthesis have been developed which control and direct the compound properties within screening libraries towards relevant areas of chemical space. In addition, strategies such as diversity oriented synthesis aim to synthesise structurally complex and diverse compounds, expanding screening collections into previously under-explored areas of chemical space. This thesis reports the development of a step-efficient, modular and highly adaptable synthetic route for the synthesis of partially saturated bicyclic heteroaromatic scffolds (Figure i). The designed route takes advantage of the large chiral pool provided by amino acids, with each scaffold synthesised in just 4-6 steps from these readily available enantiopure starting materials. The mild conditions allow for excellent functional group tolerance, thus enabling the incorporation of growth vectors for chemical elaboration from the outset, a strong advantage in the drug discovery process. Overall, 29 partially saturated bicyclic heteroaromatic compounds were synthesised based around 7 different scaffolds. These demonstrated a number of possible areas for diversifation both on and around the scaffold, including variation of functional groups (Figure i, red), double (cis-diastereoisomers) and single (R2- and R3-positions) substitution patterns, variation of the 5-membered heterocycle (Figure i, green) and increased size of the saturated ring (Figure i, blue). Furthermore, careful selection of the substituents, heterocycle and size of the saturated ring would enable the synthesis of screening libraries within the constraints of fragment-like, lead-like or drug-like structures. The final library has been incorporated into the Diamond XChem high-throughput crystallography program and initial screening has identified a weakly binding hit for Activin A.

Contamination of soils by munitions constituents is pervasive on Department of Defense operational ranges. Low-order detonations result in the heterogeneous distribution of explosives residues (ER) at shallow depths. At a limited number of ranges ER contamination of groundwater has been observed. Previous studies have shown that the downward migration of colloid-sized contaminants can significantly impact groundwater quality. The goal of this study was to investigate if colloid transport plays a role in the migration of ER contaminants. Our primary objective was to determine the transport potential of fine (<5>um) ER particles under ideal conditions for colloid transport. A secondary objective was to develop a direct detection method for the identification and quantitative analysis of particulate ER. A series of saturated transport experiments were conducted in columns (2x20 cm) packed with clean sand. 2,6- Dinitrotoluene was used as a surrogate for explosives chemicals. Experiments were conducted with both particulate and dissolved-phase DNT. Bromide and microspheres tracers were also used to characterize nonreactive transport. Particulate tracers were applied to the columns, either suspended in the influent solution, or directly to the top layer of sand, in order to more realistically replicate field conditions. Experimental results indicate that DNT movement through the columns occurred as a combination of solid and dissolved phase transport. Concentration differences between unfiltered and filtered samples indicate that particulate DNT accounted up to 30% of the total mass recovered in the effluent.

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Thesis (M.Sc.)--Memorial University of Newfoundland, 2003. / Bibliography: leaves 93-108. Also available online.

Orientador: Daniel Barrera Arellano / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos / Made available in DSpace on 2018-08-25T11:28:26Z (GMT). No. of bitstreams: 1 Chaves_KamilaFerreira_M.pdf: 1834021 bytes, checksum: 17ab04d365f81e6b3faf3237da71b9f0 (MD5) Previous issue date: 2014 / Resumo: A redução do consumo de ácidos graxos saturados (AGS) na dieta, a fim de reduzir o risco de doenças cardiovasculares, tornou indispensável a busca por substitutos desse tipo de gordura, mediante novas alternativas tecnológicas, como a dos organogéis. O uso de estruturantes em sistemas lipídicos é visto como uma alternativa promissora, pois altera as propriedades físicas de óleos vegetais, sem que ocorram modificações químicas e aumento do teor de AGS, abrindo novas possibilidades para a produção de margarinas e spreads low sat e livres de ácidos graxos trans. O objetivo desse trabalho foi produzir margarinas utilizando a tecnologia de estruturação de óleos para reduzir a quantidade de AGS em comparação às margarinas comerciais convencionais. As matérias-primas, óleo de girassol alto oleico (OGAO), óleo de soja (OS), gordura interesterificada (GI), cera de candelilla (CC) e monoacilgliceróis (M), foram caracterizadas quanto a composição, qualidade e propriedades térmicas. O processo de elaboração das margarinas teste foi realizado em escala de bancada (1 kg), a fase lipídica foi fundida a 80ºC e misturada com a fase aquosa a uma temperatura de 60ºC, sob agitação de 300 rpm. O resfriamento até 30ºC ocorreu sob agitação a 37 rpm em uma sorveteira elétrica com parede de isolamento duplo, previamente resfriada em estufa B.O.D. a 5ºC. As margarinas comerciais avaliadas apresentaram composição de AGS entre 20,52 e 23,93% e teores de lipídios de 70 a 82%. A redução do teor de AGS foi calculada considerando a diferença da quantidade de AGS das margarinas teste em comparação com a média das margarinas comerciais. Foi possível notar através do planejamento experimental que quanto menores os teores de GI, CC e M nas formulações, maior a redução de AGS. As margarinas teste apresentaram melhor estabilidade da emulsão para as temperaturas avaliadas em comparação com as margarinas comerciais. Ocorreu maior exsudação de óleo nas margarinas comerciais em comparação às margarinas desenvolvidas conforme o planejamento experimental na temperatura de 35ºC por 48 horas. As margarinas testadas com OGAO e OS apresentaram menor valor na luminosidade (*L) em comparação às margarinas comerciais. A consistência e a espalhabilidade das margarinas testadas foram significativamente iguais a pelo menos 2/3 das margarinas comerciais avaliadas e a dureza foi estatisticamente igual para todas as margarinas testadas quando comparadas com as margarinas comerciais. Conclui-se que é possível produzir margarinas, mediante a tecnologia de estruturação de óleos, utilizando CC, M e GI como estruturantes, com redução do teor de AGS de 17,3 a 36,6% para as margarinas produzidas com OS e OGAO, respectivamente, em comparação com margarinas comerciais / Abstract: Reduce the consumption of saturated fatty acids (SFA) in the diet in order to reduce the risk of cardiovascular diseases, has made indispensable the search for substitutes for this kind of fat, through new technological alternatives, such as organogels. The use of structuring agents in lipid systems has been presented as a promising alternative, once that they change physical properties without any chemical modification or increase on the amount of SFA, which open new possibilities to the production of low sat and trans free margarines and spreads. The aim of this study was to produce margarines using oil structuring technology in order to reduce the amount of SFA compared to commercial margarines. Raw materials such as high oleic sunflower oil (HOSO), soybean oil (SO), interesterified fat (IF), candelilla wax (CW) and monoacylglycerols (M), were characterized due to their quality parameters, chemical composition and thermal properties. The processing of margarines were conducted in workbench scale (1kg per batch), the oil phase was melted, heating up to 80°C, and then mixed with an aqueous phase at 60°C, under controlled speed at 300 RPM. Cooling up to 30°C occurred under shear at 37 rpm using an electrical ice cream machine with a double wall isolated cube, previously cooled to 5°C. Commercial margarines with a SFA content between 20.52 and 23.93% and 70 to 82% amount of lipids were used as comparative standars. The reduction of SFA was calculated considering the amount of SFA on trial margarines and commercial comparative standards. It was possible to notice, through an experimental design, that smaller amounts of IF, CW and M on the formulations, resulted on reduction of SFA. Trial margarines presented better emulsion stability that commercial products. A higher oil exudation occurred for commercial margarines compared to the trial samples at 35°C for 48 hours. Tested margarines using HOSO and SO presents lower luminosity values (*L) when compared to commercial ones. Consistency and spreadability of trial margarines were statistically equal to, at least, 2/3 of the commercial margarines evaluated and hardness presented no statistical difference among all trial margarines when compared to commercial margarines. In conclusion, margarines produced by oil structuring technology using CW, M and IF as structuring agents, reduced the amount of SFA from 17.3 up to 36.6% in trial margarines with SO and HOSO, respectively when compared to commercial margarines / Mestrado / Tecnologia de Alimentos / Mestra em Tecnologia de Alimentos

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