Motivation: Cardiovascular dysfunction and hypertension are some of the leading causes of morbidity and mortality in the African population. According to the World Health Organisation the increases in these diseases are escalating in developing countries. Apart from the contributory role of genetics towards the incidence of hypertension, evidence regarding lifestyle as a determinant or marker of cardiovascular diseases in this group is not well known. The interaction of psychological and physiological mechanisms can contribute towards a broader scope of behavioural physiology in the higher prevalence of hypertension in Africans. Objectives: The main objective of the research in this thesis was to compare specific coping mechanisms of Africans with regard to cardiovascular dysfunction. Methodology: Manuscripts presented in Chapters 3, 4, and 5 made use of the cross-sectional comparative epidemiological "Transition and Health during Urbanisation in South Africa" (THUSA) project. The subjects included apparently healthy African men and women, which were recruited as a convenience sample from the North West Province, South Africa. Anthropometric measurements were taken and demographic questionnaires completed. An adapted Setswana COPE questionnaire was used to classify men and women as predominantly active (AC) or passive (PC) in coping style. Subjects were further subdivided into rural and urban groups (Manuscript Two), as well as younger (≤ 40) and older (≥ 45) age groups (Manuscript Three). The General Health Questionnaire (GHQ) was used to measure subjective perception of health in all three manuscripts. Blood pressure was recorded continuously before and during application of the handgrip test using the Finapres apparatus. Subjects were classified as normotensive and hypertensive after blood pressure measurement by the Finapres and the Riva-Rocci/Korotkoff method. The emphasis in this study was on the cardiovascular reactivity values. Fasting, resting serum renin activity, cortisol, prolactin, testosterone, high density lipoprotein, triglycerides, glucose and plasma fibrinogen values were correlated with cardiovascular and psychological variables. Significant differences between variables were determined by means of variance analyses (Manuscript One and Two adjusted for age; Manuscripts One, Two and Three adjusted for resting cardiovascular data). A logistic regression analysis was performed to determine the most significant determinants of urbanisation. All THUSA subjects and parents of under-aged adolescents gave informed consent and the study - was approved by the Ethics Committee of the Potchefstroom University for Christian Higher Education. The reader is referred to the abstracts at the beginning of each separate manuscript in Chapters 3 - 5 for a description of the subjects, study design and analytical methods used in each paper. Results and conclusions of the individual manuscripts: Results from the THUSA study showed that PC men and women reported more symptoms typical of an abnormal psychological and physiological profile than AC men and women. The PC men, compared to AC men, exhibited a larger vascular reactivity response as well as larger plasma renin activity. In contrast, the AC women showed a larger non-significant vascular reactivity response than PC women. All subjects though reacted with increased vascular reactivity on the stressor. Men with a PC strategy showed enhanced vascular reactivity, a perception of poorer health and larger stressor plasma renin activity. PC women reported more depressive symptoms and younger PC women indicated a higher prevalence of hypertension than younger AC women. As a follow-up on the first manuscript, the aim was focused mainly on including the environmental effect, namely urbanisation, as possible explanatory factor for the atypical physiological AC women’s' coping style. The rural AC subjects indicated more typical active coping central cardiac responses than rural PC subjects whereas urbanised AC and PC subjects indicated greater peripheral responses and hypertension prevalence rates. In addition, the urbanised AC men and women and PC women as opposed to their rural counterparts indicated symptoms more of a distress situation with increased values of prolactin and decreased values of testosterone. This was also accompanied by a perception of poorer health in women. Results of the AC style suggests that the typical physiological AC stimulation pattern of urbanised subjects and especially the women is dissociated from the "normal" physiological AC reaction and is now exhibited as a typical PC physiological stimulation pattern. The greater vascular reactivity, hypertension prevalence, perception of poorer health and endocrine distressed profile are associated with a PC and dissociated physiological AC style in an urban context in African men and women. No differences with regard to resting blood pressure or endocrine values were obtained when the AC and PC urbanised groups were compared. Africans develop cardiovascular dysfunction/hypertension during chronic stress or urbanisation. This implies a dissociation/habituation of physiological systems of African men and women despite having an active coping strategy. Active coping is, therefore, not necessarily "successful". Results of the first two manuscripts direct further investigation concerning the effects of ageing and urbanisation on the development of cardiovascular dysfunction and metabolic syndrome indicators in gender groups. The second manuscript showed that all rural AC subjects exhibit a more typical active coping central cardiac response and that rural PC and all urbanised subjects (AC and PC) exhibit enhanced peripheral vascular responses on the - handgrip test. Where peripheral vascular responses were more expected from older individuals in Manuscript Three, the occurrence of this pattern is strengthened in the younger subjects. The greater fibrinogen values in all younger urbanised women (AC and PC) compared to rural women further strengthen the risk for the development of cardiovascular disease. Increased vascular reactivity, abdominal obesity and increased levels of triglycerides as well as perception of poorer health were apparent in the urbanised AC women, PC men and women in comparison to their rural counterparts. The typical physiological AC stimulation pattern of urbanised women is dissociated from the "normal" physiological AC responses and is now exhibited as a typical PC physiological stimulation pattern. A typical PC style in older urbanised subjects is implicated in the greater hypertension prevalence. To conclude, it seems as if young urbanised Africans, and especially women, exhibit an AC style behaviourally with a dissociated physiological AC reaction pattern. Physiologically these women resemble a typical PC physiological cardiovascular and endocrine profile. This typical PC cardiovascular stimulation pattern is strengthened by a distressed endocrine profile, significant metabolic syndrome indicators and a 'perception of poorer health. Older PC style subjects also presented a greater hypertension prevalence. In this study it seems that cardiovascular changes that appear at a younger age might be influenced by other factors including urbanisation as a lifestyle factor as well as specific coping styles. Finally, a careful suggestion is made that specific coping mechanisms could be seen as a possible risk marker in the development of the metabolic syndrome. / Thesis (Ph.D. (Physiology))--North-West University, Potchefstroom Campus, 2005.

En este trabajo abarcamos el estudio de la estructura electrónica de una serie de fulerenos denominados fulerenos endoédricos, así como también su reactividad. En este trabajo de tesis previo, se define lo que se conoce como la regla del gap (LUMO-3)-(LUMO-4), la cual indica que aquellas cajas fulerénicas vacías cuyo gap entre el tercer y cuarto orbitales desocupados sea mayor grande tendrán la capacidad de aceptar la transferencia de seis electrones desde un clúster metálico. En el capítulo 3, la regla del gap (LUMO-3)-(LUMO-4) ha sido extendida para aquellas cajas fulerénicas de hasta 100 átomos de carbono. También se ha analizado la reactividad exoédrica del M3N@D5h-C80 en una reacción de cicloadición de Diels-Alder con 1, 3-butadieno sobre los diferentes tipos de enlaces de la caja D5h-C80. En el capítulo 4 estudiamos la estructura electrónica de los fulerenos endoédricos con carburos metálicos (M2C2@C82). Se han estudiado seis isómeros de Sc2C2@C82, confirmando que su estructura electrónica se puede explicar de manera sencilla con el modelo iónico (clúster)4+@(caja)4–, adoptando el carburo metalico diferentes orientaciones dentro de la caja de C82 . En el capítulo 5 hemos estudiado la estructura y propiedades electrónicas de una otras dos famílias de fulerenos endoédricos: la de los óxideos de escandio y la de los sulfuros de escandio. Por último hemos estudiado las propiedades electroquímicas de una serie de fulerenos endoédricos con diferentes clústeres (capítulo 6). Los orbitales frontera y las propiedades redox de Sc3N@C80 son diferentes cuando son comparados con fulerenos endoédricos de metales más electro positivos (Gd e Y). / We have extended the application of the general rule for the stabilization of nitride EMFs proposed by Campanera et al. to IPR carbon cages of dimensions up to C100. This simple rule, based on the formal transfer of six electrons from the cluster to the carbon cage, can be seen as an empirical rule that is able to predict the most abundant cage isomer for all the nitride EMFs known to date. Some EMF with M2 clusters, however, seem to escape this simple rule. We have proposed six large carbon cages (from C92 to C100) with sizeable (LUMO-4)–(LUMO-3) gaps and achievable energies as candidates for encapsulating metal nitride units or M2 clusters on condition that the formal six-electron transfer and other factors are accomplished. We have confirmed that the ionic model based on the formal transfer of four electrons from the encapsulated M2C2 carbide to the carbon cage is valid for the M2C2@C82 family. We have observed that the internal metal- carbide cluster is able to rotate inside the carbon cage. Using the aforesaid ionic model we have understood the higher stability of M2C2@C82 (C3v:8) when compared to carbide endohedrals with other IPR C82 isomers. The electrochemical properties for a series of EMFs have been studied theoretically. Analogously to the neutral M3N@Ih-C80 (M = Sc and Y) systems, rotation of the M3N unit inside the fullerene cage is predicted for the neutral, oxidized and reduced states of all the nitride EMFs with IPR cages studied through this work (from Sc3N@D5h-C80 to La3N@C96).

Acrylic free radical polymerization at high temperature proceeds via a complex set of mechanisms, with many rate coefficients poorly known and difficult to determine experimentally. This problem is compounded by the large number of monomers used in industry to produce coatings and other materials. Thus, there is a strong incentive to develop a methodology to estimate rate coefficients for these systems. This study explores the application of computational chemistry to estimate radical addition rate coefficients for the copolymerization of acrylates, methacrylates and styrene. The software package Gaussian is used to calculate heats of reaction (ΔHr) values for monomer additions to monomeric and dimeric radicals, using minimum energy structures identified and characterized for the reactants and products. The Evans-Polanyi relationship is applied to estimate reactivity ratios from the relative differences in ΔHr. The validity of this methodology is tested through a comparison of calculated monomer and radical reactivity ratios for acrylate, methacrylate, vinyl acetate, ethene and styrene systems to available experimental data for copolymerization systems. The methodology is found to work for some systems while there is computational breakdown in others due to steric crowding and/or breakdown of the Evans-Polanyi relationship. / Thesis (Ph.D, Chemical Engineering) -- Queen's University, 2008-04-25 16:13:12.091 / NSERC

Altered cerebral hemodynamics contributes to mechanisms of unexplained syncope. Wecompared dynamic interaction between respiration and cerebral autoregulation in two groups ofsubjects from 28 healthy adults. Based on development of tilt-induced presyncope, subjects wereclassified as Non-Presyncopals (n=23) and Presyncopals (n=5). Airflow, CO2, Doppler cerebralblood flow velocity (CBF), ECG and blood pressure (BP) were recorded. To determine whetherinfluences of mean BP (MBP) and systolic BP (SBP) on CBF were altered in Presyncopals, thecoherencies and transfer functions between these variables and mean and peak CBF (CBFm andCBFp) were estimated. To determine influence of end-tidal CO2 (ETCO2) on CBF, relative CO2reactivity was calculated. The two primary findings were, during tilt in Presyncopals: (1) Inrespiratory frequency region, coherence between SBP and CBFp (p=0.02) and transfer functiongain between BP and CBFm was higher (MBP, p=0.01, and SBP, p=0.01) than in Non-Presyncopals. (2) In the last 3 minutes prior to presyncope, Presyncopals had a reduced relativeCO2 reactivity (p=0.005). Thus the relationship of CBF with systemic BP was more pronouncedor cerebral autoregulation was less effective preceding presyncope. This decreasedautoregulation, secondary to decreased ETCO2, may contribute in the cascade of events leadingto unexplained syncope.

Bethoxazin is a broad spectrum industrial biocide with commercial applications as a material preservative; however its mechanism of action has not been investigated. In this study, the chemical reactivity of bethoxazin towards biologically important nucleophiles was assessed with UV-Vis spectroscopy. Bethoxazin reacted with molecules containing free sulfhydryl groups such as glutathione and human serum albumin but not with amino, acetate or phenol containing compounds. Bethoxazin was shown to potently inhibit the growth of the K562 human cancer cell line with an IC50 value in the micromolar range. The sulfydryl fluorescent label ThioGlo-1 was used to investigate the biological effects of bethoxazin in K562 cells and explore its mechanism of action. Bethoxazin inhibited the formation of covalent adducts in K562 cells between the free sulfhydryl group of biomolecules and ThioGlo-1, implying that bethoxazin reacts with molecules containing free sulfhydryl groups. Likewise, when glutathione was depleted in K562 cells, by buthionine sulfoximine, high concentrations of bethoxazin were able to inhibit the formation of covalent adducts between sulfhydryl biomolecules and ThioGlo-1. The growth inhibition assay (MTS) was used to investigate the effect of continuous bethoxazin treatment versus wash out in K562 cells. The MTS assay revealed a reduction in the potency of bethoxazin due to the wash out effect, suggesting that the growth inhibition effects of bethoxazin are likely not due to glutathione depletion. A two-colour flow cytometry analysis of bethoxazin treated K562 cells for eight hours demonstrated that bethoxazin provokes necrosis induced cell death in K562 cells. Taken together, these experimental results demonstrate that the reaction of bethoxazin with proteins containing an accessible sulfhydryl group is more likely to be the mechanism of action of the cell growth inhibition effects rather than glutathione depletion.

Access to abstract restricted until 12/14/2015. / Access to thesis restricted until 12/14/2015. / Department of Chemistry

There is no abstract available for this thesis. / Department of Chemistry

A mechanism for alkene metathesis has been proposed by Chauvin, wherein metal carbenes act as catalysts for the reaction. The use and discovery of Fischer-, Tebbe-, Grubbs- and Schrock-type metal carbenes have to a certain extent proven the general mechanism. These metal carbenes showed different activity for alkene metathesis. Only Grubbs- and Schrock-type carbenes proved to be highly active for metathesis. A lot of studies have been done on the reasons for the activity, but still the main factors are unknown. In this study a molecular modelling investigation into the mechanism of the alkene metathesis reaction is done in an attempt to identify a factor(s) that can predict activity. By defining and knowing factors that contribute to activity, new catalysts can be designed that are truly active and selective. Fischer-, Tebbe-, Grubbs- and Schrocktype metal carbenes are investigated in this regard. The results of the investigation indicate that the frontier molecular orbital theory shows a possibility for prediction of alkene metathesis activity. By observing the size and location of the atomic orbital coefficients of the molecular orbital, the site of primary overlap for formation of metathesis products could be identified. The largest atomic orbital coefficient of the LUMO should be located on the metal atom. An atomic orbital coefficient should also be present on the carbene carbon for secondary overlap for formation of the metallacyclobutane intermediate. By exchanging the ruthenium in the second generation Grubbs catalyst framework the effect of the metal could be elucidated. The results clearly showed the important influence the metal atom has on the electronic properties of the catalyst complex. The results of frontier molecular orbital calculations supported the general activity trend of the four main types of metal carbenes for the metathesis of linear alkenes. By changing the metal in known catalyst frameworks a deeper understanding can be gained for the design of new alkene metathesis catalysts. / Thesis (PhD (Chemistry))--North-West University, Potchefstroom Campus, 2013

A mechanism for alkene metathesis has been proposed by Chauvin, wherein metal carbenes act as catalysts for the reaction. The use and discovery of Fischer-, Tebbe-, Grubbs- and Schrock-type metal carbenes have to a certain extent proven the general mechanism. These metal carbenes showed different activity for alkene metathesis. Only Grubbs- and Schrock-type carbenes proved to be highly active for metathesis. A lot of studies have been done on the reasons for the activity, but still the main factors are unknown. In this study a molecular modelling investigation into the mechanism of the alkene metathesis reaction is done in an attempt to identify a factor(s) that can predict activity. By defining and knowing factors that contribute to activity, new catalysts can be designed that are truly active and selective. Fischer-, Tebbe-, Grubbs- and Schrocktype metal carbenes are investigated in this regard. The results of the investigation indicate that the frontier molecular orbital theory shows a possibility for prediction of alkene metathesis activity. By observing the size and location of the atomic orbital coefficients of the molecular orbital, the site of primary overlap for formation of metathesis products could be identified. The largest atomic orbital coefficient of the LUMO should be located on the metal atom. An atomic orbital coefficient should also be present on the carbene carbon for secondary overlap for formation of the metallacyclobutane intermediate. By exchanging the ruthenium in the second generation Grubbs catalyst framework the effect of the metal could be elucidated. The results clearly showed the important influence the metal atom has on the electronic properties of the catalyst complex. The results of frontier molecular orbital calculations supported the general activity trend of the four main types of metal carbenes for the metathesis of linear alkenes. By changing the metal in known catalyst frameworks a deeper understanding can be gained for the design of new alkene metathesis catalysts. / Thesis (PhD (Chemistry))--North-West University, Potchefstroom Campus, 2013

Motivation: Cardiovascular dysfunction and hypertension are some of the leading causes of morbidity and mortality in the African population. According to the World Health Organisation the increases in these diseases are escalating in developing countries. Apart from the contributory role of genetics towards the incidence of hypertension, evidence regarding lifestyle as a determinant or marker of cardiovascular diseases in this group is not well known. The interaction of psychological and physiological mechanisms can contribute towards a broader scope of behavioural physiology in the higher prevalence of hypertension in Africans. Objectives: The main objective of the research in this thesis was to compare specific coping mechanisms of Africans with regard to cardiovascular dysfunction. Methodology: Manuscripts presented in Chapters 3, 4, and 5 made use of the cross-sectional comparative epidemiological "Transition and Health during Urbanisation in South Africa" (THUSA) project. The subjects included apparently healthy African men and women, which were recruited as a convenience sample from the North West Province, South Africa. Anthropometric measurements were taken and demographic questionnaires completed. An adapted Setswana COPE questionnaire was used to classify men and women as predominantly active (AC) or passive (PC) in coping style. Subjects were further subdivided into rural and urban groups (Manuscript Two), as well as younger (≤ 40) and older (≥ 45) age groups (Manuscript Three). The General Health Questionnaire (GHQ) was used to measure subjective perception of health in all three manuscripts. Blood pressure was recorded continuously before and during application of the handgrip test using the Finapres apparatus. Subjects were classified as normotensive and hypertensive after blood pressure measurement by the Finapres and the Riva-Rocci/Korotkoff method. The emphasis in this study was on the cardiovascular reactivity values. Fasting, resting serum renin activity, cortisol, prolactin, testosterone, high density lipoprotein, triglycerides, glucose and plasma fibrinogen values were correlated with cardiovascular and psychological variables. Significant differences between variables were determined by means of variance analyses (Manuscript One and Two adjusted for age; Manuscripts One, Two and Three adjusted for resting cardiovascular data). A logistic regression analysis was performed to determine the most significant determinants of urbanisation. All THUSA subjects and parents of under-aged adolescents gave informed consent and the study - was approved by the Ethics Committee of the Potchefstroom University for Christian Higher Education. The reader is referred to the abstracts at the beginning of each separate manuscript in Chapters 3 - 5 for a description of the subjects, study design and analytical methods used in each paper. Results and conclusions of the individual manuscripts: Results from the THUSA study showed that PC men and women reported more symptoms typical of an abnormal psychological and physiological profile than AC men and women. The PC men, compared to AC men, exhibited a larger vascular reactivity response as well as larger plasma renin activity. In contrast, the AC women showed a larger non-significant vascular reactivity response than PC women. All subjects though reacted with increased vascular reactivity on the stressor. Men with a PC strategy showed enhanced vascular reactivity, a perception of poorer health and larger stressor plasma renin activity. PC women reported more depressive symptoms and younger PC women indicated a higher prevalence of hypertension than younger AC women. As a follow-up on the first manuscript, the aim was focused mainly on including the environmental effect, namely urbanisation, as possible explanatory factor for the atypical physiological AC women’s' coping style. The rural AC subjects indicated more typical active coping central cardiac responses than rural PC subjects whereas urbanised AC and PC subjects indicated greater peripheral responses and hypertension prevalence rates. In addition, the urbanised AC men and women and PC women as opposed to their rural counterparts indicated symptoms more of a distress situation with increased values of prolactin and decreased values of testosterone. This was also accompanied by a perception of poorer health in women. Results of the AC style suggests that the typical physiological AC stimulation pattern of urbanised subjects and especially the women is dissociated from the "normal" physiological AC reaction and is now exhibited as a typical PC physiological stimulation pattern. The greater vascular reactivity, hypertension prevalence, perception of poorer health and endocrine distressed profile are associated with a PC and dissociated physiological AC style in an urban context in African men and women. No differences with regard to resting blood pressure or endocrine values were obtained when the AC and PC urbanised groups were compared. Africans develop cardiovascular dysfunction/hypertension during chronic stress or urbanisation. This implies a dissociation/habituation of physiological systems of African men and women despite having an active coping strategy. Active coping is, therefore, not necessarily "successful". Results of the first two manuscripts direct further investigation concerning the effects of ageing and urbanisation on the development of cardiovascular dysfunction and metabolic syndrome indicators in gender groups. The second manuscript showed that all rural AC subjects exhibit a more typical active coping central cardiac response and that rural PC and all urbanised subjects (AC and PC) exhibit enhanced peripheral vascular responses on the - handgrip test. Where peripheral vascular responses were more expected from older individuals in Manuscript Three, the occurrence of this pattern is strengthened in the younger subjects. The greater fibrinogen values in all younger urbanised women (AC and PC) compared to rural women further strengthen the risk for the development of cardiovascular disease. Increased vascular reactivity, abdominal obesity and increased levels of triglycerides as well as perception of poorer health were apparent in the urbanised AC women, PC men and women in comparison to their rural counterparts. The typical physiological AC stimulation pattern of urbanised women is dissociated from the "normal" physiological AC responses and is now exhibited as a typical PC physiological stimulation pattern. A typical PC style in older urbanised subjects is implicated in the greater hypertension prevalence. To conclude, it seems as if young urbanised Africans, and especially women, exhibit an AC style behaviourally with a dissociated physiological AC reaction pattern. Physiologically these women resemble a typical PC physiological cardiovascular and endocrine profile. This typical PC cardiovascular stimulation pattern is strengthened by a distressed endocrine profile, significant metabolic syndrome indicators and a 'perception of poorer health. Older PC style subjects also presented a greater hypertension prevalence. In this study it seems that cardiovascular changes that appear at a younger age might be influenced by other factors including urbanisation as a lifestyle factor as well as specific coping styles. Finally, a careful suggestion is made that specific coping mechanisms could be seen as a possible risk marker in the development of the metabolic syndrome. / Thesis (Ph.D. (Physiology))--North-West University, Potchefstroom Campus, 2005.