abstract: Mitochondria produce the majority portion of ATP required in eukaryotic cells. ATP is generated through a process known as oxidative phosphorylation, through an pathway consisting five multi subunit proteins (complex I-IV and ATP synthase), embedded inside the mitochondrial membrane. Mitochondrial electron transport chain dysfunction increases reactive oxygen species in the cell and causes several serious disorders. Described herein are the synthesis of antioxidant molecules to reduce the effects in an already dysfunctional system. Also described is the study of the mitochondrial electron transport chain to understand the mechanism of action of a library of antioxidants. Illustrated in chapter 1 is the general history of research on mitochondrial dysfunction and reported ways to ameliorate them. Chapter 2 describes the design and synthesis of a series of compounds closely resembling the redox-active quinone core of the natural product geldanamycin. Geldanamycin has been reported to confer cytoprotection to FRDA lymphocytes in a dose dependent manner under conditions of induced oxidative stress. A library of rationally designed derivatives has been synthesized as a part of our pursuit of a better neuroprotective drug. Chapter 3 describes the design and synthesis of a library of pyrimidinol analogues. Compounds of this type have demonstrated the ability to quench reactive oxygen species and sustain mitochondrial membrane potential. Described herein are our efforts to increase their metabolic stability and total ATP production. It is crucial to understand the nature of interaction between a potential drug molecule and the mitochondrial electron transport chain to enable the design and synthesis a better therapeutic candidates. Chapter 4 describes a part of the enzymatic binding studies between a molecular library synthesized in our laboratory and the mitochondrial electron transport chain using sub mitochondrial particles (SMP). / Dissertation/Thesis / Doctoral Dissertation Chemistry 2015

Paired box (PAX) gener kodar för en familj av nio stycken PAX transkriptionsfaktorer. PAX transkriptionsfaktorer är uppbyggda av en N-terminal DNA-bindande domän som utgörs av 128 aminosyror, en oktapeptid, och en C-terminal DNA-bindande domän. Studier har visat att PAX8 har en betydande roll vid utvecklingen av olika typer av tumörer. MRQ-50 är en antikropp som används inom Region Skåne för att påvisa PAX8 uttryck vid histopatologisk diagnostik. MRQ-50 riktas mot N-terminalen av PAX8 som är homolog med N-terminalen av PAX5. Detta kan leda till en korsreaktion i B-lymfocyter samt neoplasier, vilket inte är optimalt för diagnostik. Av den anledningen fortsätter forskning för att hitta en ny klon som kan ersätta MRQ-50. EP331 är en antikropp som är anpassad för detektion av det nukleära antigenet PAX8 och korresponderar till C-terminalen av human PAX8 protein. Syftet med arbetet är att optimera ett immunhistokemiskt färgningsprotokoll för detektion av PAX8 med hjälp av anti-PAX8 antikroppen EP331 och undersöka om godkända resultat kan erhållas. Detta gjordes för att ta reda på om det går att optimera ett protokoll med EP331, och om det erhålls lämpligare resultat än MRQ-50. Optimeringen gjordes på kontrollvävnader njure, tuba/äggledare och appendix och testades slutligen på patientprov med tumörvävnad. För protokolloptimering testades heat induced epitope retrieval, inkuberings tid av EP331, amplifiering, Ultra Wash i olika testomgångar. Resultatet visade att kärnor i epitelceller i proximala-, distala-njurtubuli och parietala epitelceller som klär Bowmans kapsel infärgades måttligt till starkt. De sekretoriska epitelen i tuba infärgades med stark intensitet och cilierade epitel måttligt. Infärgningen på patientprover visar godkänd specificitet, med en generell måttlig till stark intensitet. Med fler forskningsstudier av EP331 är det möjligt att primärantikroppen kan ersätta MRQ-50.

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Reading plays a significant role in society and currently there is worldwide pressure for higher literacy results. The focus of this thesis is reading motivation and how it relates to a learner's amount of reading, reading comprehension and academic achievement since these problematic constructs are attracting the interest of researchers internationally. Researchers have investigated the relationships among these constructs with a variety of results. These relationships, however, have not yet been investigated in a South African context with Afrikaans-speaking adolescent readers, and the only information available on the reading motivation of Afrikaans-speaking adolescent readers is information on their reading preferences in regard to literary texts. Hence the following three research aims were determined for this study: the compilation of a reading motivation profile of Afrikaans-speaking adolescent readers, the analysis of the relationships among Afrikaans-speaking adolescent readers' reading motivation and their amount of reading, reading comprehension and academic achievement in an Afrikaans Home Language environment, as well as the development of a reading motivation framework, particularly for use in the school and classroom environment, for these adolescent readers. The study was carried out in the post-positivistic research paradigm by means of a non-experimental quantitative research approach. Three methods of data collection were used, namely a structured questionnaire (based on the eleven reading motivation dimensions of Wigfield and Guthrie's (1997) Motivation for Reading Questionnaire, which for this purpose had been adapted for the South African context), two reading comprehension tests and obtaining the data regarding the academic achievement of the respondents. The 823 respondents that had participated in this study were the grade 9 learners (Afrikaans Home Language) of seven schools from the Dr Kenneth Kaunda district (North West Province, South Africa), selected by means of purposive sampling so that different quintiles and geographic areas were represented. Information obtained from a comprehensive literature study on relevant motivation theories, on reading motivation in practice and on the relationship among their reading motivation, amount of reading, reading comprehension and academic achievement, as well as from the results of an empirical investigation of the reading motivation of specific grade 9 learners, was used to compile a reading motivation profile of Afrikaans-speaking adolescent readers. The motivation theories on which motivation in this study was based, were the social-cognitive theory, the self-efficacy theory, the ecological system theory of human development and the expectancy-value theory, because these theories emphasise the individual's behaviour within particular social contexts and because constructs such as self-efficacy, task value and mastery, which emanate from these theories, play a cardinal role in determining suitable reading motivation strategies for specific readers. It was essential to compile a reading motivation profile of Afrikaans-speaking adolescent readers before a reading motivation framework for these adolescent readers could be compiled. The reading motivation framework recommends specific reading motivation strategies various social role-players in the school and classroom environments can implement so as to improve Afrikaans-speaking adolescent readers' reading motivation levels. The various social role-players that would influence the Afrikaans-speaking adolescent reader's reading motivation and the reading motivation strategies each of them could use, was systematised (namely the Department of Education, the school principal and management team, teachers and parents). The essence of the contribution made by this study is that a reading motivation profile of a group of Afrikaans-speaking adolescent readers (grade 9 learners) could be compiled, that clear mutual relationships among the respondents' reading motivation and their amount of reading, reading comprehension and academic achievement came to the fore from this study and that a reading motivation framework could be developed by means of which to improve the reading motivation levels of these adolescent readers. / PhD (Curriculum Development, Innovation and Evaluation), North-West University, Potchefstroom Campus, 2014

Reading plays a significant role in society and currently there is worldwide pressure for higher literacy results. The focus of this thesis is reading motivation and how it relates to a learner's amount of reading, reading comprehension and academic achievement since these problematic constructs are attracting the interest of researchers internationally. Researchers have investigated the relationships among these constructs with a variety of results. These relationships, however, have not yet been investigated in a South African context with Afrikaans-speaking adolescent readers, and the only information available on the reading motivation of Afrikaans-speaking adolescent readers is information on their reading preferences in regard to literary texts. Hence the following three research aims were determined for this study: the compilation of a reading motivation profile of Afrikaans-speaking adolescent readers, the analysis of the relationships among Afrikaans-speaking adolescent readers' reading motivation and their amount of reading, reading comprehension and academic achievement in an Afrikaans Home Language environment, as well as the development of a reading motivation framework, particularly for use in the school and classroom environment, for these adolescent readers. The study was carried out in the post-positivistic research paradigm by means of a non-experimental quantitative research approach. Three methods of data collection were used, namely a structured questionnaire (based on the eleven reading motivation dimensions of Wigfield and Guthrie's (1997) Motivation for Reading Questionnaire, which for this purpose had been adapted for the South African context), two reading comprehension tests and obtaining the data regarding the academic achievement of the respondents. The 823 respondents that had participated in this study were the grade 9 learners (Afrikaans Home Language) of seven schools from the Dr Kenneth Kaunda district (North West Province, South Africa), selected by means of purposive sampling so that different quintiles and geographic areas were represented. Information obtained from a comprehensive literature study on relevant motivation theories, on reading motivation in practice and on the relationship among their reading motivation, amount of reading, reading comprehension and academic achievement, as well as from the results of an empirical investigation of the reading motivation of specific grade 9 learners, was used to compile a reading motivation profile of Afrikaans-speaking adolescent readers. The motivation theories on which motivation in this study was based, were the social-cognitive theory, the self-efficacy theory, the ecological system theory of human development and the expectancy-value theory, because these theories emphasise the individual's behaviour within particular social contexts and because constructs such as self-efficacy, task value and mastery, which emanate from these theories, play a cardinal role in determining suitable reading motivation strategies for specific readers. It was essential to compile a reading motivation profile of Afrikaans-speaking adolescent readers before a reading motivation framework for these adolescent readers could be compiled. The reading motivation framework recommends specific reading motivation strategies various social role-players in the school and classroom environments can implement so as to improve Afrikaans-speaking adolescent readers' reading motivation levels. The various social role-players that would influence the Afrikaans-speaking adolescent reader's reading motivation and the reading motivation strategies each of them could use, was systematised (namely the Department of Education, the school principal and management team, teachers and parents). The essence of the contribution made by this study is that a reading motivation profile of a group of Afrikaans-speaking adolescent readers (grade 9 learners) could be compiled, that clear mutual relationships among the respondents' reading motivation and their amount of reading, reading comprehension and academic achievement came to the fore from this study and that a reading motivation framework could be developed by means of which to improve the reading motivation levels of these adolescent readers. / PhD (Curriculum Development, Innovation and Evaluation), North-West University, Potchefstroom Campus, 2014

Measures of workload have been developed on the basis of the various definitions, some are designed to capture the multi-dimensional aspects of a unitary resource pool (Kahneman, 1973) while others are developed on the basis of multiple resource theory (Wickens, 2002). Although many theory based workload measures exist, others have often been constructed to serve the purpose of specific experimental tasks. As a result, it is likely that not every workload measure is reliable and valid for all tasks, much less each domain. To date, no single measure, systematically tested across experimental tasks, domains, and other measures is considered a universal measure of workload. Most researchers would argue that multiple measures from various categories should be applied to a given task to comprehensively assess workload. The goal for Study 1 to establish task load manipulations for two theoretically different tasks that induce distinct levels of workload assessed by both subjective and performance measures was successful. The results of the subjective responses support standardization and validation of the tasks and demands of that task for investigating workload. After investigating the use of subjective and objective measures of workload to identify a universal and comprehensive measure or set of measures, based on Study 2, it can only be concluded that not one or a set of measures exists. Arguably, it is not to say that one will never be conceived and developed, but at this time, one does not reside in the psychometric catalog. Instead, it appears that a more suitable approach is to customize a set of workload measures based on the task. The novel approach of assessing the sensitivity and comprehensive ability of conjointly utilizing subjective, performance, and physiological workload measures for theoretically different tasks within the same domain contributes to the theory by laying the foundation for improving methodology for researching workload. The applicable contribution of this project is a stepping-stone towards developing complex profiles of workload for use in closed-loop systems, such as human-robot team iv interaction. Identifying the best combination of workload measures enables human factors practitioners, trainers, and task designers to improve methodology and evaluation of system designs, training requirements, and personnel selection