Thesis--Princeton.

Thesis (Ph. D.)--Princeton University, 1921.

Thesis (Ph. D.)--Princeton University, 1925.

iii, 246 leaves : ill. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Organic Chemistry, 1970

Thesis (Ph.D.) -- University of Adelaide, Dept. of Organic Chemistry, 1970.

No description available.

No description available.

Compound I of myeloperoxidase is capable of both one-electron oxidation and two-electron oxidation reactions. Halides and pseudohalides are the substrates for the two-electron oxidation and other compounds including a large variety of aromatic alcohols and amines can be oxidized via the single electron oxidation pathway. To investigate the catalytic mechanism of myeloperoxidase four structures of complexes of myeloperoxidase were solved. Two of them are complexes with hydroxamic acids and the other two are complexes with nitrite. Hydroxamic acids (salicylhydroxamic acid and benzylhydroxamic acid) can function as structural analogues for the aromatic alcohol and amine substrates of myeloperoxidase. The crystal structures of complexes of MPO with both hydroxamic acids have been solved at 1.85 Å resolution and their binding to myeloperoxidase is compared. The models show similar binding of their hydroxamic acid moieties but different orientations of their aromatic rings. The absence of the hydroxyl group covalently bound to the benzyl group in benzylhydroxamic acid creates an environment that does not permit the same favorable interactions with MPO when compared to salicylhydroxamic acid. These findings could explain the three orders of magnitude difference in the value of the dissociation constants of the two complexes. Nitrite has been shown to bind myeloperoxidase and also to reduce Compound I and Compound II. Crystal structures of the complex between myeloperoxidase and nitrite confirmed the binding of nitrite to the native enzyme both in the distal cavity and the chloride-binding site. The binding in the distal cavity occurred to the heme iron in the nitro mode. In the MPO-cyanide-nitrite ternary complex, nitrite had been shown to bind only at the chloride-binding site. No secondary site for nitrite binding had been seen in the distal cavity when cyanide was liganded to the iron. Overall, this study is the first to show from a crystallographic point of view a comparison in the mode of binding of the two hydroxamic acids to a mammalian peroxidase and also the binding of nitrite to a heme peroxidase.

Array-CGH analysis of the gastric cancer cell lines suggested that TXNIP loci were intact, suggesting that allelic loss might not be the major mechanism responsible for the downregulation of TXNIP in these cells. Furthermore, our data suggested that promoter hypermethylation of TXNIP may not be an important epigenetic mechanism that regulate the silencing of this gene. Chromatin immunoprecipitation (ChIP) assay revealed that SAHA induced hyperacetylation of histone H3 and H4 at the 5' flanking region of TXNIP gene, suggesting SAHA could promote TXNIP gene transcription via modification of histones located at the promoter region. Our data revealed that the loss or reduced expression of TXNIP in gastric cancer cells is associated with epigenetic histone acetylation mechanism. / Gastric cancer is a common cancer especially in Asian countries and is associated with high morbidity and mortality. Epigenetic inactivation of tumor suppressor is a common mechanism involved in carcinogenesis of a variety of human cancers and recent evidence suggested that targeting epigenetic modifications may be an approach to combat cancer. Our group and others have demonstrated frequent promoter methylation of cancer related genes in gastric cancer. In this study, we aim to identify cancer associated genes regulated by another important epigenetic mechanism, namely histone acetylation. / In addition, we demonstrated that over-expression of TXNIP significantly reduced cell migration ability and inhibited cell invasiveness in gastric cancer cells. Furthermore, absence or reduced expression of TXNIP in gastric cancer was associated with diffuse-type gastric cancer, advanced stage disease and predicted a poor disease specific survival. The findings supported that TXNIP is a functional tumor suppressor gene and may be a potential biomarker in gastric cancer. / We analyzed 25 paired gastric cancer and non-cancer gastric mucosa and found that expression of TXNIP mRNA level was reduced in 84% of gastric cancer and was significantly downregulated as compared to the paired non-cancer gastric tissues (p=0.002). Expression of TXNIP protein by western blot was down-regulated in 3 out of 5 cases. Furthermore, by immunohistochemical staining of TXNIP in tissue array containing 150 cases of gastric cancer also showed frequent down-regulation of TXNIP expression and ∼26% with complete lack of TXNIP expression. / We first showed that suberoylanilide hydroxamic acid (SAHA), a well known histone deacetylase inhibitor, has anti-proliferative effect in a panel of gastric cancer cell lines (MKN1, MKN7, MKN28, MKN45, SNU1, SNU16, AGS, N87 and KatoIII cells). We compared gene expression profiles of SAHA treated vs control AGS cells to identify a set of genes that were differentially upregulated by SAHA treatment. Based on our microarray analysis in nine gastric cancer cell lines (MKN1, MKN7, MKN28, MKN45, SNU1, SNU16, AGS, N87 and KatoIII) and normal gastric tissues, a set of commonly downregulated genes in gastric cancer cells was elucidated. Analysis of these data sets with subsequent confirmation using real-time PCR analysis, genes that were downregulated in gastric cancer cells but upregulated upon SAHA treatment were identified. Among these selected genes, Thioredoxin Interacting Protein (also known as VDUP-1/TBP2/TXNIP ) was down-regulated in all cancer cell lines tested, and its protein expression was significantly induced by SAHA treatment in a numbers of gastric cancer cell lines including AGS, MKN1, MKN45, N87 and KatoIII. Thus, we focused on the TXNIP in the subsequent studies. / Tang, Angie. / Adviser: To Ka Fai. / Source: Dissertation Abstracts International, Volume: 72-04, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 180-202). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

The present study is targeted on the optimization of the flotation conditions for the improvement of the industrial flotation practice. Part I is focused on the improvement of the flotation of Mountain Pass mine ore for the beneficiation of rare earth elements. The objective is to improve the rare earth recovery of Mountain Pass ore by developing a novel flotation reagents' scheme, meanwhile reducing the flotation temperature to a cost-efficient level and simplifying the flowsheet. Surface chemistry study by contact angle, zeta potential and microflotation tests indicate that a mixed collector consisting of oleic acid (OA) and sodium octanohydroxamate hydrate (OHA) is beneficial for rare earth flotation. More importantly, salicylhydroxamic acid (SHA) is also a promising collector due to the high selectivity. Lab-scale flotation tests using SHA as collector show that 80-90% REE recovery and <20% gangue recovery are achieved at 40°C~60°C, which yield a rougher concentrate of 30%~40% REO. A novel flotation scheme has been developed towards Mountain Pass rare earth mine. The new scheme is of both high selectivity and high recovery, meanwhile the dosage of reagent required is much less, and the flotation temperature is also significantly reduced. Interactive adsorption models are built up through FT-IR and AFM study. The interaction of collector with bastnaesite surface is illustrated. Hydroxamic acid collectors (OHA and SHA) adsorb on bastnaesite surface by forming stable chelating complex. The selectivity of collectors towards bastnaesite flotation is summarized as SHA>OHA>OA. Part II is focused on the improvement of the flotation of Resolution Copper's Superior mine ore at an elevated temperature for the beneficiation of chalcopyrite. Because the Resolution Copper ore is mined from a deep, hot, underground mine, the temperature of ROM (run of mine ore) is much higher than that of the ore usually processed in a typical open-pit copper mine. The ore temperature will still be high during flotation. It is therefore critical to carry out a systemic study on the flotation of Resolution Copper ore at elevated temperatures and clarify the impact on flotation. An overall beneficial effect is observed in high temperature flotation through a lab-scale flotation study. Further action of temperature control is not necessary. The contact angle results indicate that surface hydrophobicity is enhanced at elevated temperature, of which the surface morphology change (shown by AFM images) of xanthate adsorption species (dixanthogen) is the key factor.