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Models for delivery and price equilibrium and statistical quality control in supply chains /Cao, Min, January 2007 (has links)
Thesis (Ph. D.)--University of Hong Kong, 2007. / Also available online.
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Models for delivery and price equilibrium and statistical quality control in supply chainsCao, Min, January 2007 (has links)
Thesis (Ph. D.)--University of Hong Kong, 2007. / Title proper from title frame. Also available in printed format.
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Impacts of flexibility in delivery quantity and due date on supply chain dynamicsChan, Hing-kai. January 2006 (has links)
Thesis (Ph. D.)--University of Hong Kong, 2007. / Title proper from title frame. Also available in printed format.
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A 'Biorelevant' approach for accelerated in vitro release and in vitro-in vivo relationship of a biodegradable, naltrexone implant /Iyer, Sunil S., January 2006 (has links)
Thesis (Ph. D.)--Virginia Commonwealth University, 2006. / Prepared for: Dept. of Pharmaceutics. Bibliography: leaves 163-178. Also available online.
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Demand and supply matching with applications in air cargo and retail industries /Moussawi, Lama, January 2006 (has links)
Thesis (Ph.D.) -- University of Texas at Dallas, 2006 / Includes vita. Includes bibliographical references (leaves 117-120)
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Design, synthesis, and evaluation of dendrimers based on melamine as drug delivery vehiclesLim, Jong Doo 15 May 2009 (has links)
A variety of dendrimers based on melamine are designed, synthesized, and evaluated for drug delivery systems. The synthesis of a dendrimer, including multiple copies of four orthogonally reactive groups, is described. The three groups on the surface are nucleophilic and include four free hydroxyl groups, four tert-butyldiphenylsilyl (TBDPS) ether groups, and sixteen amines masked as tert-butoxycarbonyl (BOC) groups. The core of the dendrimer displays two electrophilic monochlorotriazines. The dendrimer above is further manipulated for in vivo biodistribution: incorporation of the reporting groups Bolton-Hunter and DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid); PEGylation for biocompatibility and size tuning. In preliminary biodistribution studies, dendrimers circulate in the blood for a longer time as the molecular weight increases, which is important to passively target tumor tissues via the EPR effect. Also, high uptake by the tumor tissues was observed in mice bearing prostate cancer xenografts. A drug delivery vehicle for the anticancer agent paclitaxel is described. This drug delivery vehicle contains sixteen molecules of paclitaxel via acid-labile ester linkage, two Bolton-Hunter groups, and sixteen monochlorotriazine groups for PEGylation. The in vitro drug release studies shows faster release of paclitaxel at lower pH in PBS.
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Synthesis and characterization of melamine-based dendrimers with potential biological applicationsCrampton, Hannah Louise 15 May 2009 (has links)
The convergent strategy towards dendrimer synthesis is well-suited to generate macromolecules with a diverse periphery, at the expense of time and effort, while the divergent strategy has historically been effective at yielding higher generation dendrimers, although they are often plagued by impurities. Both the convergent and divergent routes were applied to the synthesis of melamine-based dendrimers, offering a comparison of the routes within a system. Generation-1 dendrons heterogeneously functionalized with Boc-protected amines and hydrazones were synthesized convergently and coupled to a generation-1 tris(piperazine) core to yield a generation-2 dendrimer bearing 18 Boc-amines and three hydrazones. Although the yield for the final coupling step was rather low (56%), the yields for all intermediate steps were quite high. Attempts toward obtaining a generation-3 dendrimer through this route were unsuccessful due presumably to steric hindrance. The materials obtained showed no impurities in their 1H and 13C NMR and mass spectra, although several chromatographic purifications were necessary throughout the synthesis. A divergent strategy based on addition of a dichlorotriazine monomer to polyamine cores was used to synthesize dendrimers of generations 1-5. All intermediates and dendrimers were either purified by precipitation, or did not need purification. 1H NMR spectroscopy indicated that reactions were complete up to G4-NH2 by integration, and mass spectroscopy confirmed that assignment. HPLC and GPC of Gn-Cl dendrimers showed sharp peaks for G1-G3, but G4-Cl appeared to have a small amount of impurities that are similar in size and polarity to the fully-substituted dendrimer. The G1-G3 dendrimers were confidently assigned as pure by conventional organic chemistry standards, but the assignment of purity to higher generations remained tentative. A G1-Cl dendrimer was functionalized with imidazole, and then deprotected and PEGylated with PEG5000 to yield a water soluble dendrimer. The imidazole-capped, Boc-protected dendrimer and the deprotected dendrimer were characterized by 1H and 13C NMR spectroscopy and mass spectrometry. The degree of PEGylation on the PEGylated material could not be definitively ascertained; however, the material is capable of solubilizing very hydrophobic Zn-phthalocyanines in water.
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Design, Synthesis, and Characterization of a Novel Class of Mitochondrial Delivery Vectors: Mitochondria-penetrating PeptidesStewart, Kelly M. 23 February 2011 (has links)
Mitochondria have evolved to play a vital role in both the life and death of a eukaryotic cell, through involvement in numerous cellular functions, such as the proficient production of energy from ATP biosynthesis and the regulation of programmed cell death. As a result, dysfunction in the biochemical processes housed within this organelle is implicated in diverse diseases, including cancer, diabetes, and neurodegenerative disorders. Advancing mitochondrial medicine by probing the subcellular biochemistry or targeting therapeutics into this organelle has motivated the development of effective mitochondrial delivery vectors. Thus, the rational design of novel mitochondrial-specific molecules, inspired by the success of cell-penetrating peptides, is described, whereby short synthetic peptides that retain the ability to traverse the plasma membrane, yet with mitochondrial-specificity were engineered. By modulating the overall physicochemical properties, through substitutions with both natural and synthetic amino acids, and monitoring the intracellular localization by confocal fluorescence microscopy, the requisite thresholds for achieving mitochondrial accumulation with a cationic peptide were elucidated. These systematic studies led to the development of a novel class of cationic yet lipophilic peptides, referred to as mitochondria-penetrating peptides (MPPs), which are readily cell permeable and preferentially localize into the mitochondria of living mammalian cells. The mechanisms of cellular uptake and mitochondrial matrix accumulation were investigated and the results from these studies suggest that MPPs utilize the negative membrane potential across these biological membranes to drive translocation. In addition, the effects of various chemical perturbations on the cellular and mitochondrial uptake, such as sequence, structure of the cation moiety, and chirality, were examined. The information obtained from these studies provided insight into the important features of these peptides and led to the design of an optimized molecule displaying pyridinium salt side chains. Moreover, MPPs were shown to be effective mitochondrial delivery vectors for diverse and bioactive small molecule cargo. In conclusion, the extensive biological and chemical characterization of MPPs revealed the importance of balancing the opposing characteristics of positive charge and lipophilicity to attain preferential sequestration into mitochondria, as well as provided evidence that these peptides will be suitable as mitochondrial delivery vectors.
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Design, Synthesis, and Characterization of a Novel Class of Mitochondrial Delivery Vectors: Mitochondria-penetrating PeptidesStewart, Kelly M. 23 February 2011 (has links)
Mitochondria have evolved to play a vital role in both the life and death of a eukaryotic cell, through involvement in numerous cellular functions, such as the proficient production of energy from ATP biosynthesis and the regulation of programmed cell death. As a result, dysfunction in the biochemical processes housed within this organelle is implicated in diverse diseases, including cancer, diabetes, and neurodegenerative disorders. Advancing mitochondrial medicine by probing the subcellular biochemistry or targeting therapeutics into this organelle has motivated the development of effective mitochondrial delivery vectors. Thus, the rational design of novel mitochondrial-specific molecules, inspired by the success of cell-penetrating peptides, is described, whereby short synthetic peptides that retain the ability to traverse the plasma membrane, yet with mitochondrial-specificity were engineered. By modulating the overall physicochemical properties, through substitutions with both natural and synthetic amino acids, and monitoring the intracellular localization by confocal fluorescence microscopy, the requisite thresholds for achieving mitochondrial accumulation with a cationic peptide were elucidated. These systematic studies led to the development of a novel class of cationic yet lipophilic peptides, referred to as mitochondria-penetrating peptides (MPPs), which are readily cell permeable and preferentially localize into the mitochondria of living mammalian cells. The mechanisms of cellular uptake and mitochondrial matrix accumulation were investigated and the results from these studies suggest that MPPs utilize the negative membrane potential across these biological membranes to drive translocation. In addition, the effects of various chemical perturbations on the cellular and mitochondrial uptake, such as sequence, structure of the cation moiety, and chirality, were examined. The information obtained from these studies provided insight into the important features of these peptides and led to the design of an optimized molecule displaying pyridinium salt side chains. Moreover, MPPs were shown to be effective mitochondrial delivery vectors for diverse and bioactive small molecule cargo. In conclusion, the extensive biological and chemical characterization of MPPs revealed the importance of balancing the opposing characteristics of positive charge and lipophilicity to attain preferential sequestration into mitochondria, as well as provided evidence that these peptides will be suitable as mitochondrial delivery vectors.
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Synthesis and characterization of melamine-based dendrimers with potential biological applicationsCrampton, Hannah Louise 15 May 2009 (has links)
The convergent strategy towards dendrimer synthesis is well-suited to generate macromolecules with a diverse periphery, at the expense of time and effort, while the divergent strategy has historically been effective at yielding higher generation dendrimers, although they are often plagued by impurities. Both the convergent and divergent routes were applied to the synthesis of melamine-based dendrimers, offering a comparison of the routes within a system. Generation-1 dendrons heterogeneously functionalized with Boc-protected amines and hydrazones were synthesized convergently and coupled to a generation-1 tris(piperazine) core to yield a generation-2 dendrimer bearing 18 Boc-amines and three hydrazones. Although the yield for the final coupling step was rather low (56%), the yields for all intermediate steps were quite high. Attempts toward obtaining a generation-3 dendrimer through this route were unsuccessful due presumably to steric hindrance. The materials obtained showed no impurities in their 1H and 13C NMR and mass spectra, although several chromatographic purifications were necessary throughout the synthesis. A divergent strategy based on addition of a dichlorotriazine monomer to polyamine cores was used to synthesize dendrimers of generations 1-5. All intermediates and dendrimers were either purified by precipitation, or did not need purification. 1H NMR spectroscopy indicated that reactions were complete up to G4-NH2 by integration, and mass spectroscopy confirmed that assignment. HPLC and GPC of Gn-Cl dendrimers showed sharp peaks for G1-G3, but G4-Cl appeared to have a small amount of impurities that are similar in size and polarity to the fully-substituted dendrimer. The G1-G3 dendrimers were confidently assigned as pure by conventional organic chemistry standards, but the assignment of purity to higher generations remained tentative. A G1-Cl dendrimer was functionalized with imidazole, and then deprotected and PEGylated with PEG5000 to yield a water soluble dendrimer. The imidazole-capped, Boc-protected dendrimer and the deprotected dendrimer were characterized by 1H and 13C NMR spectroscopy and mass spectrometry. The degree of PEGylation on the PEGylated material could not be definitively ascertained; however, the material is capable of solubilizing very hydrophobic Zn-phthalocyanines in water.
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