Doctor of Philosophy / Department of Chemistry / Stefan Bossmann / Estrogen-derived DNA adducts in human could be the initiating step of breast and prostate cancer, as the scientific literature suggests. Previous studies demonstrated that 4-hydroxy-estrone (estradiol)-1-N3Adenine and 4-hydroxy-estrone (estradiol)-1-N7Guanine were the most abundant adducts found in urine of human subjects. Sensitive detection of these adducts in urine samples could lead to better breast and prostate cancer risk assessment. The standard adducts were synthesized and characterized by NMR and mass spectrometry. Since these adducts are not fluorescent at room temperature an aminomethyl (-CH2NH2) linker was introduced at the C-17 position for derivatization with fluorescence label. This linker allowed to attach highly fluorescent water soluble quantum dots (QDs) for indirect adduct detection. A direct gram-scale synthesis of highly fluorescent, photostable water soluble QDs was executed by developing a new class of 4,4’-bipyridinium salt based twin ligands with 85% and 15% of carboxylic acid and maleimide termini, respectively. These ligands not only stabilized the QDs in water but also provided versatile linkers for two labeling strategies. The twin ligands were afforded by a facile synthesis through SN2 nucleophilic substitution reaction. Labeling of adducts was achieved via a covalent coupling between the (-CH2NH2) linker and the carboxyl (-COOH) terminal ligand on the QDs. However, ELISA experiments utilizing an IgM antibody didn’t reveal any measurable signal from adduct-QD complexes suggesting that one QD is bound to a large number of adducts through –COOH terminal ligands present on QD surface. To explore the binding capabilities of QDs in more detail, a maleimide terminal ligand (a twin partner on the QDs) was synthesized to explore the thiol (-SH) functionality of thiopyrene. Preliminary ELISA showed that these QDs gave detectable fluorescent signal originating from the [pyrene-S-QD] ̶ 8E11 monoclonal antibody (mAb) complex when QD was selectively excited at 470 nm. This clearly indicates that it is necessary to develop a strategy for a distinct 1:1 labeling procedure between QD and the adduct of interest. In addition, IgG (instead of IgM) antibodies should be developed for biosensor application. The latter could afford binding of mAb in upright position, leading to an increase in surface density of mAb and better detection limit.

Doctor of Philosophy / Department of Statistics / Gary L. Gadbury / The potential for high variability in treatment effects across individuals has been recognized as an important consideration in clinical studies. Surprisingly, little attention has been given to evaluating this variability in design of clinical trials or analyses of resulting data. High variation in a treatment’s efficacy or safety across individuals (referred to herein as treatment heterogeneity) may have important consequences because the optimal treatment choice for an individual may be different from that suggested by a study of average effects. We call this an individual qualitative interaction (IQI), borrowing terminology from earlier work - referring to a qualitative interaction (QI) being present when the optimal treatment varies across ‘groups’ of individuals. At least three techniques have been proposed to investigate treatment heterogeneity: techniques to detect a QI, use of measures such as the density overlap of two outcome variables under different treatments, and use of cross-over designs to observe ‘individual effects.’ Connections, limitations, and the required assumptions are compared among these techniques through a quantity frequently referred to as subject-treatment (S-T) interaction, but shown here to be the probability of an IQI (PIQI). Their association is studied utilizing a potential outcomes framework that can add insights to results from usual data analyses and to study design features to more directly assess treatment heterogeneity. Particular attention is given to the density overlap of two outcome variables, each representing an individual’s ‘potential’ response under a different treatment. Connections are made between the overlap quantified as the proportion of similar responses (PSR) and the PIQI. Given a bivariate normal model, the maximum PIQI is shown to be an upper bound for ½ the PSR. Additionally, the characterization of a conditional PSR allows for the PIQI boundaries to be developed within subgroups defined over observable covariates so that the subset contribution to treatment heterogeneity may be identified. The possibility of similar boundaries is explored outside the normal model using the skew normal distribution. Furthermore, a bivariate PIQI is developed along with its PSR counterpart to help characterize treatment heterogeneity resulting from a bivariate response such as the efficacy and safety of a treatment.

Doctor of Philosophy / Department of Entomology / David C. Margolies and Yoonseong Park / Organisms are capable of sensing environmental conditions through diverse mechanisms. Transient receptor potential channels (TRPs) are a cation channel family that has been found to function in diverse sensing mechanisms. In this dissertation, I identified the function of several TRPs in thermosensing and mechanosensing in the red flour beetle, Tribolium castaneum. Candidate TRPs were chosen based on homology to TRPs found and studied in Drosophila melanogaster. To identify the function of candidate TRPs in T. castaneum, I suppressed the expression of target genes by RNA interference technique and investigated the phenotype of each treated beetle. Temperature is a major limiting environmental factor for organisms. I tested the function of candidate TRPs in thermotaxis (behavior) and thermal acclimation (physiology). Using bioinformatics approaches, I identified three candidate TRPs – painless, pyrexia, and trpA1 – involved in high temperature sensing. To test thermotactic behavior, I investigated beetle movement on a temperature arena with two separate temperature zones. Thermal acclimation was tested by pre-exposing beetles to either 42 °C for 10 min. When treated with double stranded RNA of TRPA1 (dstrpA1), the thermotactic response of beetles at 39 and 42 °C was reduced when compared to control groups. With pre-exposure at 42 °C, survivorship of dstrpA1-treated beetles significantly increased after one minute exposure at 52 °C compared to beetles that were not pre-exposed. With dspainless treatment, beetles showed lower response to thermal acclimation and lower long-term survivorship. Beetles treated with dspyrexia showed lower recovery after heat treatment without pre-exposure at 42 °C. To identify the function of candidate TRPs in mechanosensing, I evaluated dsRNA treated beetles for survival, walking behavior, and tonic immobility. Treatment with dsnompC and dstrpA5 resulted in failure in eclosion, causing 93 % mortality in both treatments. Survivors in dsnompC showed defects in elytra sclerotization. In dsnanchung and dsinactive treatments, adults showed abnormal walking behavior and reduced walking speed that were likely caused by defects of mechanosensing in folding of the joint between the femur and tibia. For tonic immobility, beetles with dsnanchung, dsinactive, dswaterwitch and dsick2 (insect cytokine 2) treatments showed increased sensitivity to mechanical stimulation leading to tonic immobility.

South Africa’s sluggish economic growth and limited structural transformation are at the core of the country’s high levels of unemployment and poverty. Why some countries are able to grow and others not has been the subject of much academic debate, with recent literature throwing fresh light on the phenomenon by exploring the relationship between growth and a country’s productive structure. It is argued that countries’ heterogeneous productive structures stem from differences in entrenched capabilities and know-how in producing and marketing a very specific set of products. Investigating and comparing what countries actually produce and how this supports economic development yield valuable insights into why countries differ and what their transformation priorities should be. In this study a new analytical approach is adopted to determine the potential growth paths of South Africa’s broader agricultural sector, the so-called agro-complex. Comprising 1 456 primary and processed products as well as production inputs within the food, feed and fibre segments, this broad sector makes an important contribution to economic development through its direct and indirect linkages with other economic sectors as well as its relatively high labour absorption rate. The wide-ranging economic challenges that South Africa faces have clearly gripped the country’s agro-complex. A growing dependency on imports of higher value, processed food has led to deteriorating terms of trade, while limited innovation and diversification in agricultural exports (coupled with a high proportion of re-exports) is seriously constraining the positive impact that the agro-complex could have on the country’s growth rate. In this study, the productive structure of the agro-complex is analysed through the application of the ‘product space’ framework. This methodology investigates the relatedness between products as reflected in the conditional probability of a product being exported in tandem with another product, considering all global trade flows. The proximity value, the measurement of relatedness, between all 1 456 products is used to arrive at the structure and visible evidence of an agricultural product space network. This structure allows potential diversification pathways to be analysed. Research has shown that a country’s diversification process involves moves along pathways to nearby - and thus related – ‘new’ products, which simplifies the redeployment of existing productive capabilities and knowledge. These pathways are identified according to three strategic values, namely structural transformation, market potential and employment creation. The potential for structural transformation is determined by using a product-level measure of complexity, with higher level complexity (i.e. upgrading) going to the core of structural transformation. The potential market demand is determined by examining the prospects for import substitution; producing re-exported products locally; producing new, high-potential export products; and diversifying into new markets with existing export products (with the latter two categories evident in the results of a Decision Support Model (DSM)). Finally, the potential for employment creation is analysed in the light of labour and human capital intensities at product level. The study found that South Africa’s position in the agricultural product space is relatively dispersed. This position is characterised by a proportionally high level of core competencies within the primary agricultural cluster and a limited amount of vertical linkages. Furthermore the analyses showed that, especially the products for which South Africa has developed a significant high level of specialisation such as plums and wines are located in the sparser, less promising, parts of the agricultural product space. Notwithstanding, a total of 60 realistic diversification opportunities are within “reach” from the countries core competencies in the agro-complex. The analysis on structural transformation established that the level of product complexity within the agro-complex is more important for economic development than product diversity per se. It was revealed that South Africa only ranked 69th globally with regards to the complexity of its agro-complex. It was determined that upgrading within the forestry and agro-processing of food clusters hold the most potential for improving this position. The investigation into the potential for diversification driven by market potential revealed fore mostly that the potential for substituting imports as well as re-exports with local production is limited. The market prospects for exporting “new” products and expanding the export destinations of existing products within the agro-complex is much more favourable. It was estimated that most employment creation could be derived from diversification within the primary agricultural cluster although its number of opportunities are limited. Diversification within both the primary agricultural and agro-processing of food clusters was found the have to most favourable prospects for developing the level of human capital within the agro-complex. Based on all three strategic values, the most promising diversification opportunities are located within the forestry cluster. The range of realistic opportunities within the five clusters of the agro-complex form the core for developing product-level diversification strategies. This will ultimately strengthen the position of the agro-complex and boost South Africa’s growth path for the next decade. Hence, the main contribution of this study includes the determination of the structure of South Africa’s agro-complex from a product perspective and its implications for potential growth and development. / PhD (International Trade), North-West University, Potchefstroom Campus, 2014

South Africa’s sluggish economic growth and limited structural transformation are at the core of the country’s high levels of unemployment and poverty. Why some countries are able to grow and others not has been the subject of much academic debate, with recent literature throwing fresh light on the phenomenon by exploring the relationship between growth and a country’s productive structure. It is argued that countries’ heterogeneous productive structures stem from differences in entrenched capabilities and know-how in producing and marketing a very specific set of products. Investigating and comparing what countries actually produce and how this supports economic development yield valuable insights into why countries differ and what their transformation priorities should be. In this study a new analytical approach is adopted to determine the potential growth paths of South Africa’s broader agricultural sector, the so-called agro-complex. Comprising 1 456 primary and processed products as well as production inputs within the food, feed and fibre segments, this broad sector makes an important contribution to economic development through its direct and indirect linkages with other economic sectors as well as its relatively high labour absorption rate. The wide-ranging economic challenges that South Africa faces have clearly gripped the country’s agro-complex. A growing dependency on imports of higher value, processed food has led to deteriorating terms of trade, while limited innovation and diversification in agricultural exports (coupled with a high proportion of re-exports) is seriously constraining the positive impact that the agro-complex could have on the country’s growth rate. In this study, the productive structure of the agro-complex is analysed through the application of the ‘product space’ framework. This methodology investigates the relatedness between products as reflected in the conditional probability of a product being exported in tandem with another product, considering all global trade flows. The proximity value, the measurement of relatedness, between all 1 456 products is used to arrive at the structure and visible evidence of an agricultural product space network. This structure allows potential diversification pathways to be analysed. Research has shown that a country’s diversification process involves moves along pathways to nearby - and thus related – ‘new’ products, which simplifies the redeployment of existing productive capabilities and knowledge. These pathways are identified according to three strategic values, namely structural transformation, market potential and employment creation. The potential for structural transformation is determined by using a product-level measure of complexity, with higher level complexity (i.e. upgrading) going to the core of structural transformation. The potential market demand is determined by examining the prospects for import substitution; producing re-exported products locally; producing new, high-potential export products; and diversifying into new markets with existing export products (with the latter two categories evident in the results of a Decision Support Model (DSM)). Finally, the potential for employment creation is analysed in the light of labour and human capital intensities at product level. The study found that South Africa’s position in the agricultural product space is relatively dispersed. This position is characterised by a proportionally high level of core competencies within the primary agricultural cluster and a limited amount of vertical linkages. Furthermore the analyses showed that, especially the products for which South Africa has developed a significant high level of specialisation such as plums and wines are located in the sparser, less promising, parts of the agricultural product space. Notwithstanding, a total of 60 realistic diversification opportunities are within “reach” from the countries core competencies in the agro-complex. The analysis on structural transformation established that the level of product complexity within the agro-complex is more important for economic development than product diversity per se. It was revealed that South Africa only ranked 69th globally with regards to the complexity of its agro-complex. It was determined that upgrading within the forestry and agro-processing of food clusters hold the most potential for improving this position. The investigation into the potential for diversification driven by market potential revealed fore mostly that the potential for substituting imports as well as re-exports with local production is limited. The market prospects for exporting “new” products and expanding the export destinations of existing products within the agro-complex is much more favourable. It was estimated that most employment creation could be derived from diversification within the primary agricultural cluster although its number of opportunities are limited. Diversification within both the primary agricultural and agro-processing of food clusters was found the have to most favourable prospects for developing the level of human capital within the agro-complex. Based on all three strategic values, the most promising diversification opportunities are located within the forestry cluster. The range of realistic opportunities within the five clusters of the agro-complex form the core for developing product-level diversification strategies. This will ultimately strengthen the position of the agro-complex and boost South Africa’s growth path for the next decade. Hence, the main contribution of this study includes the determination of the structure of South Africa’s agro-complex from a product perspective and its implications for potential growth and development. / PhD (International Trade), North-West University, Potchefstroom Campus, 2014

Master of Science / Food Science Institute -- Animal Science & Industry / Karen A. Schmidt / Yogurt starter and probiotic bacteria have been reported to confer health benefits to the consumer; however, to confer these health benefits yogurt and probiotic bacteria should be live and present at the recommended concentration of 6 to 8 log cfu g-1. Cegemett® Fresh (Cognis Nutrition & Health, Monheim, Germany) is a plant extract that possesses antioxidant properties. This research was divided into two experiments. The objective of experiment-I was to investigate the effect of plant extract supplementation on the redox potential (Eh) and the viability of starter cultures (Streptococcus thermophilus and Lactobacillus delbrueckii ssp. bulgaricus) in nonfat yogurt. Five yogurt samples [non-supplemented, supplemented with 0.5 or 1.0% (w/v) plant extract, or supplemented with 0.014 or 0.028% (w/w) L-cysteine.HCl] were prepared, stored at 5ºC for 50 days and analyzed weekly. L. bulgaricus counts in supplemented yogurts were > 6 log cfu mL-1 for additional 7 to 21 days compared with non-supplemented yogurt; however, S. thermophilus counts in all yogurts were > 6 log cfu mL-1 throughout the storage. Overall, Eh of plant extract supplemented yogurts were similar to non-supplemented yogurt during storage; therefore the improvement in L. bulgaricus viability cannot be attributed to the Eh alone. The objective of experiment-II was to investigate the effect of plant extract supplementation on the buffering ability of the yogurt mix, and on the viability of starter and probiotic (Bifidobacterium animalis ssp. animalis and Lactobacillus acidophilus) cultures in nonfat yogurt stored at 5ºC for 50 days. Nine yogurt samples were prepared with 0.5% (w/v) plant extract, 0.25% (w/v) sodium acetate or no supplement, fermented with starter cultures and B. animalis, L. acidophilus or both probiotics, and analyzed weekly. The plant extract and sodium acetate supplemented yogurt mixes had greater buffering capacities compared with non-supplemented yogurt mix. L. bulgaricus and L. acidophilus counts in supplemented yogurts were > 6 log cfu mL-1 for additional 7 to 35 days compared with non-supplemented yogurts. S. thermophilus and B. animalis counts were not affected by supplementation. These results suggested that greater buffering capacity could improve the viability of L. bulgaricus and L. acidophilus in yogurt during storage.

Radioactive decay of nuclei via emission of ??-particles is studied using three different theoretical approaches, viz: the quasi-bound state wavefunction approach (QSWA), the superasymmetric ??ssion model (SAFM) and the semiclassical approximation (QCA). The half-lives of the radioactive nuclei, calculated using these methods, are compared with each other and with available experimental data. The resonance wavefunction is obtained by numerically integrating the Schrödinger equation with outgoing boundary conditions. The sensitivity of the calculated decay widths to two particular parameter sets of the Woods-Saxon (WS) optical potentials are studied. Double folding (DF) model calculations to obtain the bare ??-nucleus potential have been carried out with the Reid M3Y effective nucleon-nucleon (NN) interactions. The exchange part of the interaction was taken to be of zero-range pseudo-potential and the density dependence of the NN interaction is accounted for. The effectiveness of the method is demonstrated using both even-even and odd-mass spherical nuclei. / Physics / MSC (PHYSICS)

The plasma environment of an active comet provides a unique setting for plasma physics research. The complex interaction of newly created cometary ions with the flowing plasma of the solar wind gives rise to a plethora of plasma physics phenomena, that can be studied over a large range of activity levels as the distance to the sun, and hence the influx of solar energy, varies. In this thesis, we have used measurements of the spacecraft potential by the Rosetta Langmuir probe instrument (LAP) to study the evolution of activity of comet 67P/Churyumov-Gerasimenko as it approached the sun from 3.6 AU in August 2014 to 2.1 AU in March 2015. The measurements are validated by cross-calibration to a fully independent measurement by an electrostatic analyzer, the Ion Composition Analyzer (ICA), also on board Rosetta. The spacecraft was found to be predominantly negatively charged during the time covered by our investigation, driven so by a rather high electron temperature of ~5 eV resulting from the low collision rate between electrons and the tenuous neutral gas. The spacecraft potential exhibited a clear covariation with the neutral density as measured by the ROSINA Comet Pressure Sensor (COPS) on board Rosetta. As the spacecraft potential depends on plasma density and electron temperature, this shows that the neutral gas and the plasma are closely coupled. The neutral density and negative spacecraft potential were higher in the northern hemisphere, which experienced summer conditions during the investigated period due to the nucleus spin axis being tilted toward the sun. In this hemisphere, we found a clear variation of spacecraft potential with comet longitude, exactly as seen for the neutral gas, with coincident peaks in neutral density and spacecraft potential magnitude roughly every 6 h, when sunlit parts of the neck region of the bi- lobed nucleus were in view of the spacecraft. The plasma density was estimated to have increased during the investigated time period by a factor of 8-12 in the northern hemisphere and possibly as much as a factor of 20-44 in the southern hemisphere, due to the combined effects of seasonal changes and decreasing heliocentric distance. The spacecraft potential measurements obtained by LAP generally exhibited good correlation with the estimates from ICA, confirming the accuracy of both of these instruments for measurements of the spacecraft potential.

With the advancements in acquisition and processing of seismic reflection data recorded over crystalline rocks, building three-dimensional geologic models becomes increasingly favorable. Because of little available petrophysical data, interpretations of seismic reflection data in hardrock terrains are often speculative. Potential field data modeling are sometimes performed in order to reduce the ambiguity of seismic reflection interpretations. The Kristineberg mining area in the western part of the Paleoproterozoic Skellefte Ore District was chosen to construct a pilot three-dimensional geologic model in an attempt to understand the crustal architecture in the region and how the major mineral systems operated in this architecture. To contribute to this aim, two parallel seismic reflection profiles were acquired in 2003 and processed to 20 sec with special attention to the top 4 sec of data. Several reflections were imaged and interpreted by the aid of reflector modeling, borehole data, 2.5D and 3D potential field modeling, and geological observations. Interpretations are informative at the crustal scale and help to construct a three-dimensional geologic model of the Kristineberg mining area. The three-dimensional geologic model covers an area of 30×30 km2 down to a depth of 12 km. The integrations help to interpret a structural basement to the Skellefte volcanic rocks, possibly with Bothnian Basin metasedimentary affinity. The contact is a shear-zone that separates the two units, generating large fold structures, which can be observed in the region. The interpretations help to divide the Revsund granitic rocks into two major groups based on their present shape and thickness. A large gravity low in the south is best represented by the intrusion of thick dome of Revsund granite. In the north, the low-gravity corresponds to the intrusion of sheet-like Revsund granites. In general, the structure associated with the Skellefte volcanics and the overlying metasedimentary rocks are two thrusts exposing the Skellefte volcanic rocks in the cores of hanging wall anticlinal structures. Lack of coherent reflectivity in the seismic reflection data may be due to complex faulting and folding systems observed in the Skellefte volcanics. Ultramafic sills within the metasedimentary rocks are interpreted to extend down to depths of about 5-6 km. The interpretations are helpful for targeting new VHMS deposits and areas with gold potential. For VHMS deposits, these are situated in the southern limb of a local synformal structure south of the Kristineberg mine, on the contact between the Revsund granite and the Skellefte volcanic rocks. A combination of metasedimentary and mafic-ultramafic rocks are highly gold prospective in the west, similar to observations elsewhere in the region. There are still questions that remain unanswered and need more work. New data in the study area will help to answer questions related to e.g., an enigmatic diffraction seismic signal in Profile 5 and the structural relationship between the Skellefte volcanic rocks and the Malå volcanics. Although the derived 3D geologic model is preliminary and constructed at the crustal scale, it provides useful information to better understand the tectonic evolution of the Kristineberg mining area.

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