The significantly increased copper and oxidative stress levels are characteristic hallmarks of cancer cells. These differences provide a unique opportunity for selective targeting of cancer cells. D-penicillamine (D-pen) has been proposed to generate reactive oxygen species (ROS) in presence of copper. Therefore, these studies were aimed at investigating the potential application of a currently marketed copper chelator, D-pen, as a novel cytotoxic anti-cancer agent. D-pen was shown to produce ROS, specifically hydrogen peroxide (H2O2), in the presence of cupric sulfate through a copper catalyzed oxidation reaction. During this process D-pen was converted to D-pen disulfide. The experimental proof of the H2O2 generation was conclusively shown with the aid of a novel High Performance Liquid Chromatography (HPLC) assay. The in-vitro cytotoxicity of D-pen co-incubated with cupric sulfate was examined in human beast cancer (MCF-7 and BT474) and leukemia cells (HL-60, HL-60/VCR, and HL-60/ADR). D-pen was shown to cause concentration dependent cytotoxicity in both leukemia and breast cancer cells. A direct correlation between the detection of intracellular ROS and cytotoxicity was established. The treatment of D-pen plus cupric sulfate resulted in a significant reduction in the intracellular thiol content. D-pen is highly hydrophilic and is rapidly eliminated from the body; therefore to improve the intracellular uptake and to protect the thiol group of D-pen, we carried out the synthesis and the in-vitro characterization of a novel gelatin-D-pen conjugate. It was shown that D-pen alone does not enter cells. Confocal microscopy was employed to exhibit the uptake of the novel gelatin-D-pen conjugate by cancer cells. As the cancer cells in-vitro do not accumulate the same levels of copper as reported for cancer cells in-vivo, cancer cells were pre-treated with cupric sulfate to simulate the elevated copper levels. The cupric sulfate pretreatment resulted in reduced thiol level and significantly increased cellular copper content compared to untreated cells. Whereas both free D-pen and gelatin-D-pen conjugate lacked cytotoxicity in un-treated cells, both agents caused concentration dependent cytotoxicity in cupric sulfate pre-treated leukemia cells. Therefore, it was shown that the administration of D-pen as polymer conjugate would potentially provide cytotoxicity and specificity in the treatment of cancer.

Radicals are interesting to study because of importance in so many processes such as semiconductor growth or stellar evolution. Laser induced fluorescence (LIF) and wavelength resolved emission spectra of jet cooled HPS, HAsO, AsD2, H2PS, and F2BO have been measured using the pulsed discharge jet technique. Several bands in the à 1A′′ − X̃ 1A′ transition of HPS were observed and assigned with the help of ab initio calculations. The ab initio geometries showed that HPS does not follow Walsh’s predictions for the angle change upon electronic excitation; Walsh predicts an increase in HPS upon excitation while a decrease is calculated. Ab initio Walsh-style orbital angular correlation diagrams for both electronic states show a change in correlation for some orbitals upon electronic excitation, an effect that Walsh did not predict. The à 1A′′ − X̃ 1A′ transitions were measured in HAsO and DAsO for the first time. A molecular geometry was derived for each electronic state from experimental rotational constants. The experimental geometries prove that HAsO also violates Walsh’s rules for the same reason shown in HPS. The à 2A1 – X̃ 2B1 electronic transition of AsD2 and AsHD were measured. Vibrational levels observed in emission were fit to a local mode vibrational Hamiltonian. Using the previously reported rotational constants for AsH2 and those determined for AsD2 in this work, an improved estimate of the excited state geometry was obtained. The discovery of the B̃ 2A′ − X̃ 2A′ band system of H2PS is the first report of this molecule. Both D2PS and HDPS were also observed. Ab initio calculations helped assign the transition. H2PS is one of the few tetra-atomic or larger molecules that violates Kasha’s empirical rule due to the large separation between the B̃ and à states. Finally, laser induced fluorescence spectra of the F2BO radical was observed for the first time. Previous work showed two band systems with only a tentative assignment. The measured LIF spectra confirm the identity of the two band systems as the B̃ 2A1 – X̃ 2B2 and the B̃ 2A1 – à 2B1 transitions showing F2BO also violates Kasha’s rule.

Distribution system voltage and VAR control (VVC) is a technique that combines conservation voltage reduction and reactive power compensation to operate a distribution system at its optimal conditions. Coordinated VVC can provide major economic benefits for distribution utilities. Incorporating distributed generation (DG) to VVC can improve the system efficiency and reliability. The first part of this dissertation introduces a direct optimization formulation for VVC with DG. The control is formulated as a mixed integer non-linear programming (MINLP) problem. The formulation is based on a three-phase power flow with accurate component models. The VVC problem is solved with a state of the art open-source academic solver utilizing an outer approximation algorithm. Applying the approach to several test feeders, including IEEE 13-node and 37-node radial test feeders, with variable load demand and DG generation, validates the proposed control. Incorporating renewable energy can provide major benefits for efficient operation of the distribution systems. However, when the number of renewables increases the system control becomes more complex. Renewable resources, particularly wind and solar, are often highly intermittent. The varying power output can cause significant fluctuations in feeder voltages. Traditional feeder controls are often too slow to react to these fast fluctuations. DG units providing reactive power compensation they can be utilized in supplying voltage support when fluctuations in generation occur. The second part of this dissertation focuses on two new approaches for dual-layer VVC. In these approaches the VVC is divided into two control layers, slow and fast. The slow control obtains optimal voltage profile and set points for the distribution control. The fast control layer is utilized to maintain the optimal voltage profile when the generation or loading suddenly changes. The MINLP based VVC formulation is utilized as the slow control. Both local reactive power control of DG and coordinated quadratic programming (QP) based reactive power control is considered as the fast control approaches. The effectiveness of these approaches is studied with test feeders, utility load data, and fast-varying solar irradiance data. The simulation results indicate that both methods achieve good results for VVC with DG.

Titanium and titanium based alloys are widely used in dentistry and orthopedics to replace hard tissue and to mend broken bones. It has become a material of choice due to its low density, high strength, good biocompatibility and its capacity to integrate closely with the bone. Today, modern materials and surgical techniques can enable patients to live longer, and aid in maintaining or regaining mobility for a more fulfilling life. There are, however, instances where implants fail, and one of the primary causes for implant failure is infection. This thesis deals with two possible ways of reducing or eliminating implant associated infections; TiO2 photocatalysis, where a surface can become antibacterial upon irradiation with UV light; and incorporation of silver, where a subsequent release of silver metal ions result in an antibacterial effect. For the TiO2 photocatalysis strategy, a simple and cost effective chemical oxidation technique, using hydrogen peroxide (H2O2) and water, was used to create an active TiO2 surface on titanium substrates. This surface was shown to effectively degrade an organic model substance (rhodamine B) by generating reactive oxygen species (ROS) under UV illumination. However, it was shown that Ti-peroxy radical species remaining in the surface after the H2O2-oxidation process, rather than generation of ROS from a heterogeneous photocatalytic process, was responsible for the effect. This discovery was further exploited in a TiO2/H2O2/UV system, which demonstrated synergy effects in both rhodamine B degradation tests and in antibacterial assays. For the silver ion release strategy, a combinatorial materials science approach was employed. Binary Ag-Ti oxide gradients were co-deposited in a reactive (O2) environment using a custom built physical vapor deposition system, and evaluated for antibacterial properties. The approach enabled synthesis and composition-structure-property evaluation unlikely to have been achieved by traditional means, and the gradient coatings demonstrated antibacterial properties against both S. aureus and S. epidermidis according to silver ion release. The release was shown to depend more on structural features, such as surface area, crystallinity and oxidation state, than on composition. Ag-Ti oxide gradients were also evaluated under UV illumination, as Ag deposits on crystalline TiO2 can enhance photocatalytic properties. In this work, however, the TiO2 was amorphous and UV illumination caused a slight reduction in the antibacterial effect of silver ions. This was attributed to a UV-induced SOS response in the S. epidermidis bacteria. The results of this thesis demonstrate that both TiO2 photocatalysis, or UV induced activation of Ti-peroxy radical species, as well as incorporation of silver are viable antibacterial strategies for titanium biomaterials. However, their clinical applications are still pending risk-benefit analyses of potential adverse host tissue responses.

There is a need for simulation methodologies for multiphase three-dimensional microstructures that can be used in numerical simulations of material behavior or in exact computation of effective properties using microstructural correlation functions. Specifically, the methodology must be able to generate verifiably realistic microstructures, with complex morphology accurately represented. Striving to address that need, the research presented here develops a general microstructure simulation toolbox for multiphase two- and three-dimensional microstructures consisting of one connected phase and one or more particulate phases. Previous work by other researchers has found successful solutions to a variety of special cases of the general problem, but most of them are intended for binary microstructures, and nearly all simulate only two-dimensional microstructures. The toolbox presented here attempts to exceed those limitations. Its framework is a Metropolis stochastic-optimization routine running a simulated-anneal schedule, with particle position coordinates defining the configuration space and a range of forms available for the ﾓenergyﾔ? function. The toolbox allows several parameterizations of the microstructure, supplying all elementary properties (phase volume fractions, mean sizes, etc.) and some non-elementary properties (distributions of elementary properties, properties relating to inter-phase distances and morphology) of microstructures as possible parameters. The toolbox is able, as one special case, to simulate realistic microstructures of uniaxially compacted mixtures of elemental Al-Ti-B powders and achieve basic microstructure-processing correlation. Statistical tests involving microstructural correlation functions bear out the realism. The toolbox is also able to generate virtual microstructures for the same system, for use in the design of experiments (which are in fact high-strain-rate impact simulations), and for evaluating hypotheses involving achievable material properties. The Al-Ti-B powder compacts are potential advanced energetic materials that, when subjected to high-strain-rate impact (which may or may not constitute shock compression), explosively release heat by anaerobic reaction according as certain incompletely understood conditions are met or not. The study of those conditions and the mechanism of reaction initiation (carried out by a collaborator) is the specific application that the simulations in this work cater to. To ensure realistic morphology in simulated Al-Ti-B microstructures, this work included reconstruction (carried out by montage serial sectioning) of large three-dimensional volumes of Al-Ti and Al-B binary compacts for two sets of powders that yielded actual 3 D Ti and B particle images. Accordingly, advancement of the experimental technique of montage serial sectioning and a quantitative characterization of the real powder microstructures also formed part of this research. While only examples from Al-Ti-B powders are used throughout this work, it is clear that the methods will apply to other similar systems.

The research presented in this dissertation explores the possibility of using colloidal indium tin oxide (ITO) nanoparticle solutions to direct write transparent conducting coatings (TCCs), as an alternative route for TCC fabrication. ITO nanoparticles with narrow size distribution of 5-7 nm were synthesized using a non-aqueous synthesis technique, and fabricated into films using spin coating on substrates made from glass and fused quartz. The as-coated films were very transparent (>95% transmittance), but highly resistive, with sheet resistances around 10¹³ Ω/sq . Pre-annealing plasma treatments were investigated in order to improve the electrical properties while avoiding high temperature treatments. Composite RIE treatment recipes consisting of alternating RIE treatments in O₂ plasma and in Ar plasma were able to reduce the sheet resistance of as spin coated ITO films by 4-5 orders of magnitude, from about 10¹³ Ω/sq in as-coated films to about 3 x 10⁸ Ω/sq without any annealing. Plasma treatment, in combination with annealing treatments were able to decrease the sheet resistance by 8-9 orders of magnitude down to almost 10 kΩ/sq , equivalent to bulk resistivity of ~0.67 Ω.cm. Investigation into effectiveness of various RIE parameters in removing residual organics and in reducing the sheet resistance of colloidal ITO films suggested that while reactive ion annealing (RIE) pressure is an important parameter; parameters like plasma power, number of alternating O₂-Ar RIE cycles were also effective in reducing the residual organic content. Impedance spectroscopy analysis of the colloidal ITO films indicated the dominance of the various interfaces, such as grain boundaries, insulating secondary phases, charge traps, and others in determining the observed electrical properties.

These are the proceedings of the International Workshop on Reactive Concepts in Knowledge Representation (ReactKnow 2014), which took place on August 19th, 2014 in Prague, co-located with the 21st European Conference on Artificial Intelligence (ECAI 2014).

Permeable reactive barriers are considered among the most promising technologies for contaminated soil and groundwater remediation. Zero-valent iron (ZVI), hydroxyapatite (HA), and organic compost, with (OM) and without (OMx) dextrose/sulfate were assessed in column studies for their ability to attenuate chromium (Cr) or cadmium (Cd). PVC columns were packed with the reactive media and Cr or Cd solutions were pumped through the columns at concentrations of 5, 50 and 200 mg/l. These media were also assessed for their abilities to attenuate Cr and Cd from a contaminated soil. The order of Cr removal was: ZVI > OMx > OM > HA. The ZVI treatment maintained a removal rate of > 95% throughout the study. All treatments used for Cd removal had a removal rate of 98% across all treatments. The ZVI was the only treatment capable of retaining any of the mobile soil Cr and Cd from the contaminated soil. / Department of Natural Resources and Environmental Management

Clients of reactive systems often change their priorities. For example, a human user of an email viewer may attempt to display a message while a large attachment is downloading. To the user, an email viewer that delayed display of the message would exhibit a failure similar to priority inversion in real-time systems. We propose a new quality attribute, attentiveness, that provides a unified way to model the forms of redirection offered by application-level reactive systems to accommodate the changing priorities of their clients, which may be either humans or systems components. Modeling attentiveness as a quality attribute provides system designers with a single conceptual framework for policy and architectural decisions to address trade-offs among criteria such as responsiveness, overall performance, behavioral predictability, and state consistency.

Increased reactive oxygen species (ROS) have been reported to be at the centre of various diseases. Although several reports have implicated elevated levels of ROS in the pathogenesis of diabetes mellitus, the early detection of ROS is still not attainable. This limitation causes difficulty in the early diagnosis of ROS related disorders. The presence of high levels of ROS was reported to result in differential expression of antioxidant genes involved in protecting cells from their deleterious effects. Among the antioxidant genes that are expressed, it was postulated that expression of metallothioneins (MTs) are also induced. MTs are low molecular weight, cysteine-rich proteins involved in metal homeostasis and reported to harbour antioxidant function. The aim of this investigation was to explore MTs as biomarkers for elevated levels of ROS in whole blood of type 2 diabetic (T2D) individuals. The level of ROS in diabetic, non-diabetic as well as individuals at risk of developing T2D was determined via the use of biochemical assays. Real-Time PCR was utilised to analyse the expression of MTs and the presence of MT proteins was analysed via the ELISA. In this study it was observed that diabetic individuals had elevated levels of ROS. However, no significant difference in the expression of MTs and the presence of MT proteins between the diabetic and non-diabetic individuals was observed. In vitro experimental conditions indicated that MT expression is induced by elevated levels of ROS. In pathological conditions the ROS-dependent induction of MT expression needs to be elucidated further. It therefore can be suggested that MTs can not yet be utilised as biomarkers for the detection of elevated levels of ROS in pathological conditions with ROS aetiology. This investigation also highlights the fact that blood is not an optimal medium in which this objective can be attained. / Thesis (Ph.D. (Biochemistry))--North-West University, Potchefstroom Campus, 2005.