Benzene is a ubiquitous environmental pollutant and a known human leukemogen. Early-life exposure to environmental carcinogens, including benzene, may lead to genomic instability in the fetus, ultimately leading to an increased risk for the development of childhood cancers including leukemia. It is possible that exposure to benzene results in DNA damage that may either be left unrepaired or be repaired erroneously causing genotoxicity. The first objective of this study was to determine if exposure of fetal hematopoietic cells to p-benzoquinone, a known toxic metabolite of benzene, increased DNA recombination in the pKZ1 model of mutagenesis. A significant increase in recombination was observed following exposure to 25 μM and 50 μM p-benzoquinone for 2, 4, 8, and 24 hours. A significant increase in recombination was also observed following exposure to 25 μM p-benzoquinone for 30 min, 45 min, and 1 hour, but not 15 min as compared to vehicle alone. Secondly, this study determined if exposure of fetal hematopoietic cells to p-benzoquinone resulted in DNA damage using γ-H2A.X as a marker for DNA double strand breaks and 8-hydroxy-2’-deoxyguanosine as a marker of oxidative DNA damage. A significant increase in γ-H2A.X foci formation was observed following exposure to 25 μM p-benzoquinone for 30 min, 45 min and one hour. Exposure of fetal hematopoietic cells to 25 μM p-benzoquinone did not significantly increase oxidative DNA damage at any of the examined time points. The third objective of this study was to determine whether or not reactive oxygen species were involved in the observed increase in DNA damage and recombination. Exposure to 25 μM p-benzoquinone for 15 min and 30 min, but not 45 min or one hour, led to an increase in reactive oxygen species production as measured by 5-(and-6)-chloromethyl-2-7-dichlorodihydrofluorescein diacetate fluorescence. Additionally, pretreatment with 400 U/mL PEG-catalase, an antioxidative enzyme, attenuated the increases in both DNA recombination and DNA double strand breaks as compared to treatment with p-benzoquinone alone. These studies indicate that p-benzoquinone is able to induce DNA damage and recombination in fetal hematopoieitic cells and that reactive oxygen species and oxidative stress may be important in the mechanism of toxicity. / Thesis (Master, Pharmacology & Toxicology) -- Queen's University, 2010-07-23 15:44:05.381

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The increase in the contamination of ground-water (GW) with nitrates in both developing and developed countries mainly results from agricultural activities and improper sanitation systems, and is a recent phenomenon that has become a source of great health concern, particularly in regions where people rely on the ground-water as their primary water source. Due to the advantages of using Permeable Reactive Barriers (PRB) including its cost-effectiveness as well as its capability to remove or mitigate the spread of large spectrum of contaminants (including nitrates), a significant increase has been observed in the use of this subsurface treatment technology compared to other methods. However, identifying more economic and reliable reactive media to be used instead of the costly conventional PRB materials is now of key importance. Two local soils namely Berea Red Sand (BRS) and Umgeni Sand (US) were the main focus of this research. In addition to these soils, Zero Valent Iron (ZVI) was also used in this study. Through the use of batch experiments the feasibility of the nitrate reduction was investigated by five substrates including 100% ZVI, 100% BRS, 100% US, mix of 75% ZVI + 25% BRS, and mix of 50% ZVI + 50% BRS. Five concentrations of nitrate synthetic solution including 10 mg/l, 25 mg/l, 50 mg/l, 100 mg/l, and 500 mg/l were used to simulate nitrate-contaminated ground-water. All the batch experiments were performed under semi-aerobic and uncontrolled pH conditions, and only one solid/liquid ratio of 1:10 was used. The two mixes (mix of 75% ZVI + 25% BRS, and mix of 50% ZVI + 50% BRS) exhibited a nitrate removal efficiency of 100%, with all the different initial concentrations that were used with it; besides these two mixes, none of the other substrates showed this performance. 100% ZVI; however, managed complete nitrate reduction when the 10 mg/l and 25 mg/l concentrations were used. Finally, it was concluded that the benefits of using BRS in combination with other materials such as ZVI in the PRB field are promising. / Thesis (M.Sc.Eng.)-University of KwaZulu-Natal, Durban, 2013.

Infection with challenge virus standard-11 (CVS) strain, a laboratory fixed rabies virus strain, induces neuronal process degeneration in both in vivo and in vitro models. CVS-induced axonal swellings of primary rodent dorsal root ganglion neurons are associated with 4-hydroxy-2-nonenal staining indicating a critical role of oxidative stress. Mitochondrial dysfunction is one of the most important causes of oxidative stress. We hypothesized that CVS infection induces mitochondrial dysfunction leading to oxidative stress. We investigated the effects of CVS infection on several mitochondrial parameters in different cell types. CVS infection increased electron transport chain capacity, Complex I and IV activities, but did not affect Complex II-III, citrate synthase, and malate dehydrogenase activities. CVS maintained normal oxidative phosphorylation capacity and proton leak, indicating a tight mitochondrial coupling. Possibly as a result of enhanced Complex activity and efficient coupling, a high mitochondrial membrane potential was generated. CVS infection reduced the intracellular ATP level and altered the cellular redox state as indicated by high NADH/NAD+ ratio. CVS infection was associated with a higher rate of hydrogen peroxide production. We conclude that CVS infection induces mitochondrial dysfunction leading to ROS overgeneration, oxidative stress and neuronal process degeneration.

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The catalytic N-oxidation of alkylpyridines, a reaction which uses hydrogen peroxide as the oxidizing agent and the water soluble phosphotungstic acid as the catalyst, is a reaction employed in the pharmaceutical industry. The safety concerns of this process revolve around the decomposition of hydrogen peroxide and the liquid-liquid phase separation of the reacting mixture. The decomposition of hydrogen peroxide is an undesired reaction parallel to the desired N-oxidation and is responsible for: 1) a high potential for runaway due to the condition sensitivity of the peroxide group, 2) a potential over-pressurization of the reaction vessel during a runaway due to the production of oxygen, and 3) the enrichment with oxygen of the flammable alkylpyridine environment. The presence of an organic phase and an aqueous phase occurs in a wide range of conditions and results in: 1) a dramatic reduction in the reaction selectivity, and consequently in the efficiency, due to the additional mass transfer constrains imposed by the phase separation, and 2) the safety of the process being seriously compromised because most of the catalyst remains in the aqueous phase, excessively promoting the decomposition of hydrogen peroxide over the N-oxidation. With these concerns in mind, this research aimed to determine conditions for an inherently safer and more efficient N-oxidation reaction and focused on three key targets: i) the possibility of reducing the extend of the decomposition of hydrogen peroxide, thus leading to an inherently safer process, ii) the study of phase equilibrium so as to enable the identification of conditions that increase the efficiency of the N-oxidation and reduces the hazards, and iii) the evaluation of safety parameters that will allow for the control of a potential runaway reaction. Two alkylpyridines were considered: 2-methylpyridine which represents the case of a homogeneous reacting mixture and 2,6-dimethylpyridine to study the two-liquid phase separation effects. The methodology employed calorimetric studies to assess the runaway behavior and to determine the conditions that favor the N-oxidation, and for the N-oxidation of 2,6-dimethylpyridine, thermodynamic studies were incorporated to evaluate the conditions for phase separation.

Reactive hazard associated with chemicals is a major safety issue in process industries. This kind of hazard has caused the occurrence of many accidents, leading to fatalities, injuries, property damage and environment pollution. Reactive hazards can be eliminated or minimized by applying Inherently Safer Design (ISD) principles such as "substitute" or "moderate" strategies. However, ISD would not be a feasible option for industry without an efficient methodology for chemical hazard assessment, which provides the technical basis for applying ISD during process design. In this research, a systematic chemical hazard assessment methodology was developed for assisting the implementation of ISD in the design of inherently safer process. This methodology incorporates the selection of safer chemicals and determination of safer process conditions, which correspond to "substitute" and "moderate" strategies in ISD. The application of this methodology in conjunction with ISD technique can effectively save the time and investment spent on the process design. As part of selecting safer chemicals, prediction models were developed for predicting hazardous properties of reactive chemicals. Also, a hazard index was adopted to rate chemicals according to reactive hazards. By combining the prediction models with the hazard index, this research can provide important information on how to select safer chemicals for the processes, which makes the process chemistry inherently safer. As part of determining safer process conditions, the incompatibility of Methyl Ethyl Ketone Peroxide (MEKPO) with iron oxide was investigated. It was found that iron oxide at low levels has no impact on the reactive hazards of MEKPO as well as the operational safety. However, when iron oxide is beyond 0.3 wt%, it starts to change the kinetics of MEKPO runaway reaction and even the reaction mechanism. As a result, with the presence of a certain level of iron oxide (> 0.3 wt%), iron oxide can intensify the reactive hazards of MEKPO and impose higher risk to process operations. The investigation results can help to determine appropriate materials for fabricating process equipment and safer process conditions.

One of the fundamental aspects of a virtual environment is the virtual agents that inhabit them. In many applications, virtual agents are required to perceive input information from their environment and make decisions appropriate to their task based on their programmed reaction to those inputs. The research presented in this thesis focuses on the reactive behaviour of the agents. We propose a new control architecture to allow agents to behave autonomously in navigation tasks in unknown environments. Our behaviour-based architecture uses fuzzy logic to solve problems of agent control and action selection and which can coordinate conflicts among different operations of reactive behaviours. A Fuzzy Associative Memory (FAM) is used as the process of encoding and mapping the input fuzzy sets to the output fuzzy set and to optimise the fuzzy rules. Our action selection algorithm is based on the fuzzy α-level method with the Hurwicz criterion. The main objective of the thesis was to implement agent navigation from point to point by a coordination of planning, sensing and control. However, we believe that the reactive architecture emerging from this research is sufficiently general that it could be applied to many applications in widely differing domains where real-time decision making under uncertainty is required. To illustrate this generality, we show how the architecture is applied to a different domain. We chose the example of a computer game since it clearly demonstrates the attributes of our architecture: real-time action selection and handling uncertainty. Experimental results are presented for both implementations which show how the fuzzy method is applied, its generality and that it is robust enough to handle different uncertainties in different environments. In summary, the proposed reactive architecture is shown to solve aspects of behaviour control for autonomous virtual agents in virtual environments and can be applied to various application domains.