Chan Siu Hong. / "December 1999." / Thesis (Ph.D.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references (p. 172-192). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Licentiatafhandling.

Recent concern over the potential environmental impact of highway construction and repair materials on surface and ground waters has lead to extensive laboratory screening and subsequent testing of a set of new materials and waste amended mixes. As part of Phase II of a three-phase project for the National Cooperative Highway Research Program, a fate and transport model for the assessment of this impact has been written. The model predicts concentrations and loads of contaminants as well as toxicities for the leachates in both surface and subsurface environments. The model addresses four specific "reference environments": an impermeable highway surface, a permeable highway surface, a vertical piling, and a filled borehole. Six materials are examined in detail: crumb rubber asphalt concrete. SEMASS asphalt concrete, foundry sand asphalt concrete, ammonical copper zinc arsenate treated wood, and methyl methacrylate deck sealer. A statistical approach to relating toxicity to the concentration of a chemical "surrogate" forms the basis for prediction of toxicity in the leachates. All fate and transport prediction methods are based on physical and mathematical descriptions of the near-highway environment. Surface runoff is calculated using kinematic wave theory coupled with leaching, photolysis and volatilization, flow through pavement cracks is based on continuity, and subsurface transport is based on a plug flow model with linear or Freundlich sorption and biodegradation. Explicit finite difference numerical methods are used for both surface leaching and subsurface transport. A search engine is provided for examination of all laboratory results. / Graduation date: 1999

2,5-diketopiperazines peculiar heterocyclic system found in several natural products constitutes a rich source of new biologically active compounds. The wide spectrum of their biological properties points to various therapeutic possibilities. Introduction of structural rigidity, resulting in diketopiperazine derivatives containing a pyridine ring that can form an intramolecular hydrogen bond,and shows an interesting activity. In our research, we hope to probe further the importance of structural rigidity with regards to biological activity. We hope to replace the hydrogen bonding between the pyridine ring and amide nitrogen with a covalent link. This will further restrict the rotation and isomerization of the Z-double bond.

Ph.D.

Ph.D.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2002. / Härtill 6 uppsatser.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniv. / Härtill 5 uppsatser.

Diss. (sammanfattning) Göteborg : Göteborgs universitet, 2010.

Neuropathic pain is a prevalent disease with no effective, safe treatments and limited knowledge on the mechanisms involved. One target for neuropathic pain treatment may be the blockade of Dynorphin A (Dyn A). Dyn A is a unique endogenous ligand that possesses well-known neuroinhibitory effects via opioid receptors and neuroexcitatory effects that are mediated through the bradykinin 2 receptors (B2Rs). Extensive SAR was carried out to develop a ligand for the blockade of the excitatory actions of Dyn A at the B2R. A lead ligand was able to block Dyn A-induced hyperalgesia in naïve animals and was effective in a neuropathic pain model. However, the ligand was susceptible to enzymatic degradation. In an effort to increase the stability, modifications of the ligand using non-natural amino acids were performed. Analogues substituted at or near the N-terminus with a D-isomer retained binding at the receptor as well as provided a large increase in stability. These ligands were also found to be non-toxic in a cell toxicity assay. Dyn A has been found to not activate the classical signaling of the B2R, PI hydrolysis or Ca²⁺ mobilization. In an effort to determine Dyn A's signaling, a study was done examining up-regulation of phosphorylated proteins. It was found that Dyn A did not activate; pERK, 7 PKC isoforms or PKA. A well known B2R antagonist, HOE140, was found to have low affinity at rat and guinea pig brain B2Rs but high affinity in the guinea pig ileum. Further examination revealed that this discrepancy in binding may arise from a different isoform of the B2R that has not been previously examined. To date, we have discovered Dyn A analogues that have high affinity for the B2R, are very stable, and have low toxicity. The signaling pathway is still not fully understood, but further studies are underway. Also, there is evidence that the B2R in which the analogues are interacting at may be a different form than what has previously been described. Targeting this different isoform of the B2R with our current stable ligands may provide beneficial therapeutics for the treatment of neuropathic pain without the cardiovascular liabilities.