Bibliography: leaves 170-196. / xix, 199 leaves, [84] leaves of plates : ill. (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / The results presented in this thesis establish the growth-suppressive activity of the human GAS1 gene and provide the first direct evidence that GAS1 can inhibit the growth of tumours. In addition, this study demonstrates that the antiproliferative effect of GAS1 are mediated by a p53 dependent pathway and that functional inactivation of p53 by either mutation and/or overexpression of the MDM2 oncogene product inhibits the GAS1 mediated growth-suppression. / Thesis (Ph.D.)--University of Adelaide, Dept. of Physiology, 1997?

Errata inserted. Bibliography: leaves 98-120. This study is concerned with the identification of genes related to the very early stages of meiosis when homologous pairing occurs. A cDNA library is prepared at the premeiotic interphase and prophase stages of meioses. Differential screening is used to identify and select clones showing preferential expression in anthers at early meiosis. Two selected clones are chosen for further analysis and to investigate a possible role in chromosome pairing.

Trichloroethene (TCE) is the most frequently detected organic contaminant in groundwater, is classified as a probable human carcinogen, and exhibits toxicological effects on the human endocrine, immune, developmental, and reproductive systems. While significant research efforts have been devoted to the development of strategies for remediating TCE-contaminated groundwater, their advancement is currently hindered by limitations in current methodologies for measuring in situ reductive dechlorination rates, especially for sorbing solutes. This dissertation describes the development, evaluation, and demonstration of a method for measuring in situ reductive dechlorination rates that utilizes single-well, "push-pull" test technology. Initial field tests indicated that trichlorofluoroethene (TCFE) could be used as a surrogate for TCE in push-pull tests since (a) TCE and TCFE were transported similarly and (b) TCFE underwent reductive dechlorination by a pathway analogous to that of TCE while retaining the fluorine label. Because TCFE and TCE experienced sorption at the selected field site, a novel data analysis technique called "forced mass balance" (FMB) was developed to obtain in situ transformation rates of sorbing solutes from push-pull test data. The FMB technique was evaluated by quantifying errors in rates derived by applying FMB to push-pull test data generated by a numerical model. Results from simulated tests indicated that an example in situ rate for the reductive dechlorination of TCFE, which was obtained by applying FMB to field data, was underestimated relative to the true in situ rate by 10%. The utility of the rate-determination method presented in this dissertation was demonstrated by using it to evaluate the effectiveness of a chemical amendment, namely fumarate, at enhancing in situ reductive dechlorination rates in TCE-contaminated groundwater. Reductive dechlorination rates increased following three consecutive additions of fumarate in all five of the tested wells. The development of the rate-determination method described in this dissertation advances the state of bioremediation technology because methods for measuring in situ transformation rates are needed to both assess the potential for natural attenuation and to quantify the effects of bioremediation techniques in the field. / Graduation date: 2003

A pilot scale demonstration of a biological permeable barrier was conducted in a pentachlorophenol-contaminated aquifer at a wood preserving facility. A permeable reactor was constructed to fit within a large diameter well. Arranged in series, a cylindrical reactor 24" x 36" (0.61 x 0.91m) (diameter x height) was partitioned to provide three biological treatment zones. Pentachlorophenol (PCP) biodegradation was evaluated under several environmental conditions using a mixed microbial consortium supported on ceramic saddles. Imitation vanilla flavoring (IVF), a mixture of propylene glycol, guaiacol, ethyl vanillin and sodium benzoate, served as the electron donor. In the absence of exogenous substrate, PCP was not degraded in the inoculated permeable barrier. Substrate addition under oxidizing conditions also failed to initiate PCP removal. Anaerobic conditions however, promoted in-situ PCP degradation. PCP reductive dechlorination resulted in the transient production of 3,4,5-trichlorophenol through sequential ortho dechlorinations. Continued carbon reduction at the meta and para positions resulted in 3,4-dichlorophenol and 3,5-dichlorophenol production. Complete removal of all intermediate degradation products was observed. Reactor operation was characterized through two independent laboratory and field companion studies. Experiments were conducted to evaluate (1) the effect of supplemental electron donor concentration (IVF) and (2) the effect of sulfate, a competitive electron acceptor on PCP reductive dechlorination. Results from laboratory and field conditions were consistent. (1) In the presence of an exogenous electron donor, PCP degradation was independent of supplemental donor concentration (10, 25, 50, 100 mg COD/L). However, a comparatively slower rate of PCP degradation was observed in the absence of electron donor. (2) The presence of sulfate was not inhibitory to PCP degradation. However, compared to systems evaluated in the absence of sulfate, slower rates of PCP transformation were observed. Passive operation and low energy requirements, coupled with potential contaminant mineralization suggest that the biological permeable barrier is a highly effective tool for subsurface restoration. / Graduation date: 2000

Graduation date: 1995

No description available.

In the past decades our knowledge concerning breast cancer progression from ductal carcinoma in situ (DCIS) to invasive cancer has grown rapidly. However, molecular factors driving the progression are still largely unknown. In the first study, we investigated tumor evolution in breast cancer by analyzing TP53 mutation status in tumors from various stages of the disease. Presence of the same TP53 mutations in both DCIS and invasive components from the same tumor indicates same cellular origin. The role of mutant TP53 in the progression of breast cancer is less clear and may vary between subtypes. In the second study, we studied the prognosis of basal-like DCIS in a large population-based cohort. Basal-like DCIS was associated with about doubled but not statistically significant risk for local recurrence compared with the other molecular subtypes. Molecular subtype was a better prognostic parameter than histopathological grade. In the third study, we studied markers in primary DCIS in relation to type of recurrence. Interestingly, recurrences after an ER-/HER2+, ER negative or EGFR positive primary DCIS were more often of the in situ type. The molecular subtype ER+/HER2+, FOXA1 positivity and FOXC1 positivity were risk factors for any recurrence. In the fourth study, we proposed a histological classification system for a new entity: neoductgenesis. We also evaluated histologic criteria for neoductgenesis. According to our criteria, good agreements among pathologists were achieved. Neoductgenesis was related to more aggressive tumor biology and to mammographic features. The result indicates potential benefits for women earlier considered having pure DCIS but later diagnosed as breast carcinoma with neoductgenesis, suggesting a need to develop appropriate treatment regiments. Our findings have to be repeated and the relation to prognosis warrants further studies.

Natural killer (NK) cells, lymphocytes of the innate immune system, can recognize a wide array of cells via several receptors families such as Ly49 and NKR-P1. The Nkrp1 gene family encode for C-type lectin-like receptors which can recognize their ligands, Clr, on target cells. Nkrp1 and Clr genes are intertwined in the NK gene complex and are thus inherited together. The Nkrp1-Clr genes in 129S6 and BALB/c mouse strains show significant sequence polymorphism compared to those of C57BL/6 mice while the overall gene organization and gene number are conserved. RT-PCR was utilized to study the expression of individual Nkrp1-Clr genes. In situ hybridization was performed to validate expression results from RT-PCR, as well as to verify the cell types in which Nkrp1-Clr genes are expressed. Surprisingly, our expression studies reveal an interesting pattern of expression of Nkrp1 and Clr genes not only in lymphoid tissues but also in the epithelial cells of the intestine, kidney, eye and lung, the myocytes of the heart and skeletal muscle, and possibly some endothelial cells, indicating novel functions of NK cells in these tissues.

Abstract Chapter 1 provides an overview of this study and a literature review. Emphasis is put on the materials used, the different processes available to synthesize polymer-clay nanocomposites, analytical methods to characterize nanophase materials and on the impact of the nanophase on the final physical properties of polymer-clay nanocomposites. Chapter 2 discusses PE-clay nanocomposites which were synthesized using metallocene and Ni-diimine catalysts through in-situ polymerization. Morphological studies were carried out by XRD, SEM, EDX, and TEM to investigate the intercalation and exfoliation mechanism. Prior to its injection into the polymerization reactor, montmorillonite (MMT) was treated with triisobutyl aluminum and undecylenyl alcohol (UOH). Triisobutyl aluminum (TIBA) can react with hydroxyl groups on the surface of MMT and UOH is able to react with TIBA on the MMT surface. An alkoxy bond is generated by the reaction of the hydroxyl groups of UOH with the TIBA on the surface of MMT. A single site catalyst was then supported on the MMT/TIBA/UOH support, generating a MMT/TIBA/UOH/CAT system. The free vinyl groups of the surface UOH molecules can be copolymerized with ethylene, leading to the formation of chemical bonds between the MMT surface and polyethylene (PE). Ethylene polymerizations with the MMT/TIBA/UOH/CAT system were compared with ethylene polymerization with unsupported catalysts. The resulting PE-clay nanocomposites were analyzed with electronic and optical microscopes to confirm the nanophase distribution of MMT platelets in the polymer matrix. TEM images showed that the exfoliated MMT layers appeared as single layers or aggregated layers in the polyethylene matrix. After Soxhlet extraction with boiling 1,2,4-trichlorobenzene, the morphology of the residue particles remaining the thimble showed polymer fibrils stemming from the MMT surface, providing direct evidence of the chemical bonds between MMT surfaces and polymer matrix. Some residue particles also show PE-clay hybrid fibers between the particles. Through SEM/EDX analysis, it was confirmed that the fiber’s composition possessed silicone atoms together with carbon atoms. Chapter 3 discusses the results of in-situ polymerizations in gas-phase. The same catalyst systems and polymerization conditions discussed in Chapter 2 for slurry polymerization were applied to the gas-phase polymerization in order to investigate the particle fragmentation mechanism. After gas-phase polymerization at atmospheric pressure, the surface morphologies were investigated by SEM and TEM. In the case of the MMT/TIBA/UOH/Cp2ZrCl2 system, small particles (< 10m) were shattered from the larger particles (> 100 m) in the early stages of polymerization. After 24-hours of continuous polymerization, polymer fibrils growing from the inside of the MMT particles were observed by SEM. After further investigation with TEM, the cross-section profile of the particles showed curved bundles of MMT platelets, which illustrates exfoliation starting from the edges of the MMT particles. The MMT/TIBA/UOH/Ni-diimine system shows a different surface morphology after polymerization. In the early stages of the polymerization, polymer films were generated from the inside of the particles. After further polymerization, the MMT particles shattered and formed aggregates of PE-clay nanocomposites, similar to the ones proposed in the multigrain model. Chapter 4 discusses the copolymerization of ethylene and acrylonitrile. Ethylene/acrylonitrile copolymers were produced in the presence of a Ni-diimine/EASC catalyst system without the use of supports. Polymerizations of ethylene and acrylonitrile showed comparable activities in low concentrations of acrylonitrile. However, in higher concentrations, acrylonitrile induced a reductive elimination of the alkyl groups in the activated nickel-diimine catalyst. Conclusively, GPC analyses showed that acrylonitrile behaves as a chain transfer agent, showing reductive elimination of alkyl groups in the catalytic active center. The polymerization product morphology was analyzed by SEM and TEM. Polyacrylonitrile domains were observed in the polyethylene matrix and confirmed its nanosize distribution in the polyethylene matrix. DSC analysis of ethylene/acrylonitrile copolymers shows that an exothermic reaction takes place from 300 C to 370 C. This exotherm band detected by DSC can be related to the cyclization and aromatization of the nitrile groups of polyacrylonitrile. Through IR analysis of the ethylene and acrylonitrile polymer under high temperatures, this cyclization and aromatization was confirmed to be the cause of the decrease of the nitrile band (at 2244 cm-1) and increase of the vinyl bands (at 1640 cm-1). In addition, thermal treatment in DSC and successive XRD analysis showed the formation of the lamellar structures in the polyethylene matrix, reported as lamellar formation of polyacrylonitrile due to cyclization and aromatization of nitrile groups. The decomposition temperatures measured by TGA increased up to 50 C due to the presence of the nitrile groups in the polymer matrix. Tensile testing showed that the modulus increased, together with the yield strength and elongation. This phenomenon supports that strong interfacial interactions exist between the polyethylene matrix and polyacrylonitrile domains, as confirmed by TEM and IR analysis. Chapter 5 introduces the idea of acrylonitrile as a clay surface modifier. MMT was treated with acrylonitrile, using the same modification method of MMT that was applied in the MMT/TIBA/UOH/CAT system in Chapter 2. The nitrile groups in PE-MMT/TIBA/AN/CAT composites were confirmed at 2244 cm-1 by IR analysis. DSC analysis of PE-MMT/TIBA/AN/CAT showed that an exothermic reaction takes place from 300 C to 375 C. Successive DSC analysis with the same sample showed a new glass transition temperature band, induced by the reduction of polymer chain mobility. The basal diffraction band disappeared due to the exfoliation of MMT. Tensile tests showed an increase in modulus, without sacrificing the yield strength and elongation of PE-clay hybrid composites. Through these analyses, it was confirmed that strong interfacial forces exist between the polyethylene matrix and MMT layers in these PE-clay nanocomposites.

In order to preserve groundwater as a viable source of drinking water, remedial measures must be applied where appropriate. The application of the various remedial technologies is site and contaminant dependent. Differing geology, subsurface soil, groundwater geochemistry, type of contaminant present, cost and even accessibility to the site are all considerations when selecting an appropriate remedial system. At many sites oxygen is a limiting factor for aerobic degradation of many organic compounds like methyl tert butyl ether (MTBE) and hydrocarbons found in diesel and fuel oil, etc. (Nyer et al, 2002). Mechanisms limiting the success of getting the oxygen out of the passive release well include: · Slow chemical diffusion of oxygen in water; · Limited cross section of the groundwater flowing into the well and advecting oxygenated water back into the aquifer; and · Generally weak transverse dispersion, both horizontal and vertical, during subsequent advection of the oxygenated water in the porous media. These issues must be recognized even in the design of a passive release well remediation system. For example, a typical remedial objective is to deliver dissolved oxygen across the width and vertical extent of a contaminant zone in an aquifer. The width of the oxygen plume around the injection well defines how many oxygen-release wells are required to create a curtain of oxygen. Cost-effective design dictates fewer wells, while effective coverage may dictate more wells placed closer together. Thus, understanding the transverse width over which significant oxygen is passively released to the aquifer (the “radius of influence”) is a critical design parameter and the focus of this thesis. Due to the difficulty in getting a passively released dissolved oxygen plume to transversely encompass the total width of a contaminant plume, other more efficient means of introducing oxygen into the subsurface are required. Injecting amended water directly into a release well would increase the transverse distance in which dissolved oxygen would spread. A series of experiments were conducted at CFB Borden to assess the efficacy of an oxygen releasing technology called the iSOC™. The experiments were all conducted in the same manner, by connecting a tank of oxygen to the iSOC™ unit, which then was placed in a release well and allowed to run in experiment 1 for 103 days, experiment 2 for 132 days and experiment 3 for 29 days. iv Dissolved oxygen concentrations were measured at varying time intervals throughout each experiment using an Orion dissolved oxygen probe. Results of each of the three experiments were very similar in that dissolved oxygen was only detected in a very narrow plume (10 cm to 25 cm in width) within 1 m of the release well. The presence of BTEX, BOD and COD within the groundwater and soil at the site were investigated to assess if presented a significant enough sink for the oxygen and thereby limiting the transverse growth of the dissolved oxygen plume. Groundwater results indicated that while dissolved oxygen was utilized for BTEX degradation and to overcome the natural oxygen demand (both BOD and COD) at the site, the amount of oxygen released into the aquifer would have satisfied both of these processes. The COD of the soil at the site presented a higher oxygen demand than the groundwater and presented a greater limiting factor to the transverse growth of the oxygen plume. By releasing oxygen passively with the iSOC™ only a small transverse portion of the Borden aquifer was likely influenced. This limitation has been noted in general for passive release technologies (Wilson & Mackay, 1995). While the iSOCÔ technology develops very high oxygen levels in the groundwater in the release well, it does not overcome the hydrogeological constraint of limited transverse dispersion. Thus, a high oxygen concentration is delivered to a very narrow segment of the aquifer. Overall, transverse dispersion has a minimal impact on a passively release oxygen plume, particularly in close proximity to the release well, but once the plume has migrated a distance away from the release well the effect of transverse dispersion increases. The oxygen demand of an aquifer can also limit the effect of transverse and longitudinal dispersion. If a site has a high chemical or biological oxygen demand the released gas will be consumed before dispersion can have an effect on the plume. By injecting nutrient rich water into a release well the water will forcibly overcome any influence transverse dispersion will have in and around a release well, thereby relying on longitudinal dispersion to create a larger area for contaminant degradation to occur.