Converging evidence indicates that SOD1 aggregation is a common feature of mutant SOD1 (mSOD1)-linked FALS, and seems to be directly related to the gain-of-function toxic property. However, the mechanisms of protein aggregation are not fully understood. To study the contribution of modification on cysteine residues in SOD1 aggregation, we systematically examined the redox state of SOD1 cysteine residues in the G37R transgenic mouse at different stages of ALS and under oxidative stress induced by H2O2. Our data showed that under normal circumstances, cysteine 111 in SOD1 is free. Under oxidative stress, it is prone to oxidative modification by providing the thiolate anion (S-). With the progression of ALS, increased levels of oxidative insults facilitated the oxidation of thiol groups of cysteine residues. Human mutant SOD1 could generate an upper shifted band in SDS-PAGE, which turned out to be a Cys111-peroxidized SOD1 species. We also found that at different stages of ALS, accumulated oxidative stress facilitated the aggregates formation, which were not mediated by disulfide bond. The oxidative modification of cysteine 111 may promote the formation of disulfide bond-independent SOD1 aggregates. In addition, we investigated the correlation between nitrosative stress and S-nitrosylation of protein disulfide isomerase (PDI) in the mechanism of aggregates formation. Our data showed that up-regulated inducible nitric oxide synthase (iNOS) generated high levels of nitric oxide (NO), which induced S-nitrosylation of PDI with the progression of ALS in the spinal cords of mSOD1 transgenic mice. This correlation was confirmed by treating SH-SY5Y cells with NO donor SNOC to trigger the formation of S-nitrosylated PDI (SNO-PDI). When mSOD1 was overexpressed in SH-SY5Y cells, iNOS expression was up-regulated, NO generation was increased consequently. Furthermore, both SNO-PDI and mSOD1 aggregates were detected in these cells. Blocking NO generation with NOS inhibitor N-nitro-L-arginine (NNA) attenuated the S-nitrosylation of PDI; the formation of mSOD1 aggregates was inhibited as well. We conclude that NO-mediated S-nitrosylation of PDI is highly linked to the accumulation of mSOD1 aggregates in ALS.

Polymer surfaces were modified by exposure to a silent discharge plasma, by exposure to UV radiation and by chemical functionalisation. Additionally, the silent discharge treatment of alkali halide disks was investigated. Employing XPS and IR, the silent discharge treatment of poly (phenylmethylsilane) and poly (cyclohexylmethylsilane) thin films was found to result in the formation of a carbonaceous SiO(_x) layer. Oxidation occurred faster and to a larger degree in the case of the aromatic polysilane. A XPS study of the UV irradiation of poly (phenyhnethylsilane) thin films in the presence of CCI(_4) vapour revealed the formation of a chlorinated silicon species. The analysis of aged samples showed that this initially formed product was unstable in moist air. The silent discharge treatment of alkali halide disks (KCI, KBr, KI) was studied in ambient air, as well as in dried and humidified gases (artificial air. He, N(_2), O(_2)). IR and XPS were used as analytical methods, hi most cases nitrate and halogenate were formed upon treatment in air. Depending on the reaction conditions treated KI disks sometimes showed the presence of nitrite as an additional or as the main product. In oxygen atmospheres halogenate was formed as the exclusive product. Treatments in the remaining atmospheres did not lead to product formation. The presence of water vapour in the feed gas increased the amount of product. Changes in the IR spectra of the nitrate species upon storage in a desiccator and after exposure to heat were found and monitored. Pentafluoropropionic anhydride was tested for its suitability as a vapour phase labelling reagent for hydroxyl groups on polymer surfaces. Derivatised films were analysed by XPS and IR. Using Polyvinyl alcohol as a model polymer the reaction proceeded fast and quantitative. Moreover, the cross-reaction with a number of polymers containing functionalities other than hydroxyl was studied. The reaction with nylon 6,6 was investigated m detail. The vacuum photodegradation of polyethersulfone upon irradiation with the full and a selected part of a Hg (Xe) lamp spectrum was studied. The volatile products were identified with in-situ quadrupole mass spectrometry. Monitoring the intensities of some products in subsequent irradiation phases provided evidence for a crosslinking process. In samples irradiated with the complete lamp spectrum crosslinkmg occurred faster. Additionally, the XP spectra of the corresponding samples revealed a stronger modification which became most obvious in the presence of a reduced sulfur species.

The abundant nuclear enzyme poly (ADP-ribose)polymerase (P ARP) catalyses the formation of long homopolymeric chains of ADP-ribose, utilising NAD+ as a substrate, as the immediate cellular response to DNA damage. PARP recognises a damaged section of DNA and initiates polymer synthesis, which is believed to act as a signal to effect the repair of the lesion. A selective, potent PARP inhibitor could block the recognition, and hence repair, of DNA damage induced by cancer chemotherapy. Since increased DNA repair is regarded as a mechanism whereby tumour cells can become resistant to treatment, PARP inhibitors have therapeutic potential as resistance modifying agents. From a study of PARP inhibitors such as 3-hydroxybenzarnide (A), benzimidazole derivatives (B) were proposed as inhibitors of the enzyme, and the synthesis and biological evaluation of a series of such molecules has been achieved. Substituted 2-aryl benzirnidazoles have proved to be highly potent PARP inhibitors (B;R= 4'NO2Ph, IC5o= 59 nM), under a permeabilised cell assay the nitro phenyl derivative (B; R= 4'N02Ph) is the most potent compound reported to date (IC50= 19 nM). 2-Methyl benzirnidazole-4-carboxamide (B; R= Me) has been shown to potentiate the in vitro cytotoxicity of the antitumour agent temozolomide in L1210 cells, and the synthesis of benzimidazole inhibitors suitable for pre-clinical in vivo eluation has also been investigated, This thesis demonstrates that benzimidazole PARP inhibitors have promising potential for clinical development as resistance modifying agents.

This thesis details electrical and physical measurements of pulsed laser deposition-applied thin film coatings of Alumina, Ceria, and Yttria-stabilized Zirconia (YSZ) on a LiNi0.5Mn0.3Co0.2O2 (NMC) cathode in a Lithium ion battery. Typical NMC cathodes exhibit problems such as decreased rate performance and an opportunity for increased capacity exists by raising operation voltage beyond the electrolyte stability window. Very thin (~10 nm) coatings of stable oxides provide a pathway to solve both problems. As well, the electrochemical impedance spectra of the uncoated and coated cells were measured after different numbers of cycles to reveal the property variation in the cathode. Further understanding of the mechanism of rate performance enhancement and chemical protection by thin oxide coatings will continue to improve battery capability and open up new applications. Ceria-coated Li-NMC cells show the best capacity and rate performance in battery testing. Through electrochemical impedance spectroscopy (EIS), the surface film resistance was found to remain stable or even drop slightly after repeated cycling at high voltage. CeO2 is proposed as a coating for Lithium ion battery cathodes owing to its high chemical stability and the demonstrated but not yet well understood electrical conductivity. Alumina-coated cathode shows comparable performance as that of the uncoated cell in the early stage of the test, but through the course of testing the rate capability and recoverable capacity is improved. This is possibly due to Al2O3?s well-known abilities as HF scavenger and chemically inert nature. YSZ-coated cathode performs worse than the uncoated ones in terms of capacity, rate capability, and EIS-related figures of merit. The reason for the poor performance is not yet known, and repeatability tests are under way to verify performance. High voltage cycling reveals no obvious difference in irreversible loss between the coated or uncoated cells. The reason for the lack of distinction could be the relatively small percentage of surface coating compared to the thick doctor-blade processed cathode layer.

Thesis (MPsych(Clin))--University of South Australia, 2000

The recently discovered mesoporous molecular sieve MCM-41 was synthesized, modified, and characterized and proposed as an alternative adsorbent for VOC control. The synthesis conditions for pure-silica and aluminosilicate MCM-41 were optimized as follows: 4.5Na2O:30SiO2:5.2C16H33(CH3)3N + :2500H2O and 7.5Na2O:30SiO2:xAl2O3:7.2C16H33(CH3)3N + :3500H2O (x < 1), respectively, and at 373 K for 4 days. Our studies showed that MCM-41 is not stable in the presence of water vapor. For example, a hydrothermal treatment of MCM-41 at 723 K for 2 hour resulted in 50 % of structure collapses. Again, when a template-free MCM-41 sample was exposed to air with a relative humidity of 60 % for three months, almost total pore structure collapses were observed. Adsorption equilibrium results showed that MCM-41 has a narrow pore size distribution and exhibits extraordinary pore volume compared to the classical microporous adsorbents, such as molecular sieves and activated carbons. Despite the impressive adsorption capacities of this material, the Type IV isotherm behavior requires the VOCs, in the gas phase, to be at high partial pressure. This is not the case with most industrial VOC streams. A real VOC stream requires an adsorbent with not only a high adsorption capacity but also a high adsorption affinity at a low VOC concentration. To overcome the above mentioned two problems, both the surface chemistry and the pore-opening sizes of MCM-41 were modified. To modify the surface chemistry, one has to better understand the surface chemistry. Our pioneering study of the surface chemistry of MCM-41 using FTIR, 29 Si CP/MAS NMR, pyridine-TPD, and TGA demonstrated that three types of silanol groups, i.e. single, (SiO)3Si-OH, hydrogen-bonded, (SiO)3Si-OH---OH-Si(SiO)3 and geminal, (SiO)2Si(OH)2 are distributed over the surface of MCM-41. The number of silanol groups per unit nm 2 , aOH, varies between 2.5 and 3.0 depending on the template-removal method. To improve the hydrothermal stability and enhance the hydrophobicity, the surface chemistry of MCM-41 was modified by silylation. Though both the free and hydrogen-bonded SiOH groups were found to be the active sites for adsorption of pyridine with desorption energies of 91.4 and 52.2 kJ mol -1 , respectively, only the free SiOH groups are highly accessible to the silylating agent, chlorotrimethylsilane. The surface coverage of the modifying agent was found to has a linear relationship with the surface free silanol groups which can be controlled by different heating temperatures. Modification by silyaltion can significantly improve hydrophobicity and stability. Rehydration/dehydration experiments demonstrate that the surface-silylated MCM-41 is highly tolerable to water vapor due to the complete replacement of surface-hydrophilic silanols. A novel modification method, namely selective tailoring (ST), was developed to tailor the pore-opening sizes of MCM-41 (rather than the entire pores). The novelty is that only the pore mouths at both ends of a cylindrical pore of MCM-41 was modified by deposition of some alkoxides. By doing so, the types of adsorption isotherms of VOCs can be changed from Type IV to Type I while the pore volume can be significantly preserved. This is of course significance in VOC removal since the adsorption affinity has been drastically enhanced. Adsorption equilibria and kinetics for VOCs in the pore-opening-modified MCM-41 materials were measured, modeled and compared to that of activated carbons and hydrophobic molecular sieves. The pore-modified MCM-41 has a much higher adsorption capacity than that of the traditional microporous adsorbents such as activated carbons and molecular sieves. The adsorption equilibrium data fit the Langmuir-Uniform distribution (Unilan) models very well. Upon the equilibrium parameters being obtained and considering the pore structure of our pore-modified MCM-41 adsorbents, the kinetic data were further modeled using the literature-existed models recently developed by Do and coworkers, i.e. the constant surface diffusivity macropore, surface and micropore diffusion (CMSMD) model and the macropore and surface diffusion (MSD) model. Results demonstrated that the CMSMD model can predict our kinetic uptake curves reasonably fine. Some key kinetic parameters including pore and surface diffusivities, apparent diffusivity, activation energy for adsorption, and pore tortuosity factor can be readily obtained. The porosity of the MCM-41 materials were primarily evaluated using the traditional methods based on nitrogen adsorption/desorption data. Results indicated that the BJH method always underestimates the true pore diameter of MCM-41. An comparison plot (t-plot or as-plot) method was suggested and improved. Plotting of nitrogen adsorption data at 77 K versus the statistical film thickness reveals three distinct stages, with a characteristic of two points of inflection. The steep intermediate stage is caused by capillary condensation occurred in the highly uniform mesopores. From the slope of the section after condensation, the external surface area can be obtained. Therefore, the true surface area of the mesopores is readily calculated. The linear portion of the last section is extrapolated to the adsorption axis of the comparison plot, and this intercept is used to obtain the volume of the mesopores. From the surface area and pore volume, average mesopore diameter is calculated, and the value thus obtained is in good agreement with the pore dimension obtained from powder X-ray diffraction measurements. The principle of pore size calculation, the thickness of adsorbed nitrogen film, and the problems associated with the BJH method were discussed in detail. It has been found that at a given relative pressure, the smaller the pore radius, the thicker the adsorbed film. Thermodynamics analysis established that the stability of the adsorbed film is determined by interface curvature and the potential of interaction between adsorbate and adsorbent. A semi-empirical equation is proposed to describe the state of stable adsorbed films in cylindrical mesopores. It is also shown to be useful in calculations of pore size distributions of mesoporous solids. The desorption of four representative volatile organic compounds (VOCs), i.e. n-hexane, cyclohexane, benzene, and methanol from MCM-41 were also investigated and compared with the hydrophobic zeolite, silicalite-1, using the technique of temperature programmed desorption (TPD). The desorption energies of these organics to MCM-41 were evaluated and compared with the adsorption isosteric heats. The affinity of organics to MCM-41 and silicalite-1, which represents surface hydrophobicity/hydrophilicity were studied and discussed. Results showed that only one desorption peak can be found for all organics from MCM-41, different from that from the microporous adsorbents (activated carbons and hydrophobic molecular sieves). The activation energies for desorption of non-polar molecules are slightly higher than their latent heats of evaporation, whereas the activation energy for desorption of methanol is well above its latent heat of evaporation. These results are consistent with those derived from the adsorption isotherm measurements. The very high activation energy for the desorption of methanol is due to the hydrogen bonds between methanol molecules and silanol groups over MCM-41 surfaces. The affinity of volatile organics to MCM-41 are in the order of methanol > n-hexane > benzene > cyclohexane.

Thesis (M.A.)--University of Nevada, Reno, 2007. / "August, 2007." Includes bibliographical references (leaves 27-31). Online version available on the World Wide Web.

Thesis (Ph.D.)--University of Melbourne, Dept. of Accounting and Business Information Systems, 2006. / Typescript. Includes bibliographical references (leaves 213-229).

Thesis (Ph. D.)--Ohio State University, 2007.

Dissertation (Ed.D.)--University of Toledo, 2008. / Typescript. "Submitted as partial fulfillment of the requirements for The Education Doctorate Degree in Educational Administration and Supervision." Bibliography: leaves 156-169.