Genomic instability, in the form of gene mutations, insertions/deletions, and gene amplifications, is one of the hallmarks in many types of cancers and other inheritable genetic disorders. Trinucleotide repeat (TNR) disorders, such as Huntington’s disease (HD) and Myotonic dystrophy (DM) can be inherited and repeats may be extended through subsequent generations. However, it is not clear how the CAG repeats expand through generations in HD. Two possible repeat expansion mechanisms include: 1) polymerase mediated repeat extension; 2) persistent TNR hairpin structure formation persisting in the genome resulting in expansion after subsequent cell division. Recent in vitro studies suggested that a family A translesion polymerase, polymerase θ (Polθ), was able to synthesize DNA larger than the template DNA. Clinical and in vivo studies showed either overexpression or knock down of Polθ caused poor survival in breast cancer patients and genomic instability. However, the role of Polθ in TNR expansion remains unelucidated. Therefore, we hypothesize that Polθ can directly cause TNR expansion during DNA synthesis. The investigation of the functional properties of Polθ during DNA replication and TNR synthesis will provide insight for the mechanism of TNR expansion through generations.

In South Africa, many young children from poor social and economic backgrounds are cared for at home by parents or guardians who are themselves illiterate. This leads to poor educational outcomes later in life. Yet there are many privileged teenagers with access to mobile technologies who spend a greater portion of their spare time interacting on ubiquitous social media platforms. This presents an opportunity whereby the poor educational outcomes referred to previously could be addressed by applying a technology solution providing social media-based homework support by privileged teenagers to underprivileged younger children. However, most applications designed for use by children are designed by adults, with little understanding of the user requirements of the target end users. This research explores the following question: How can a cross-age tutoring system be designed for implementation on a social networking platform to support numeracy and literacy skill acquisition? The main contribution of this research was the definition of the Cooperative design by Children for Children (CD2C) Design Framework, a blueprint of how a cross-age tutoring system could be co-designed by children of different age groups and life circumstances. The CD2C Design Framework was derived as an abstraction of the second contribution of this research, the TitanTutor, an artifact designed using co-operative inquiry method and the Design Science Research approach. The third novelty of this research was contribution to Design Science Research theory, with the addition of new theory that states that cooperative design by children from different age groups and life circumstances is tempered by socio-environmental context and power relations between the co-design partners. This work provided important contributions to researchers in the areas of Cooperative Inquiry (CI), Human Computer Interaction (HCI), and Design Science Research (DSR). Future researchers could extend the CD2C Design Framework to make it even more abstract, thereby making it universally applicable to any co-design scenario. / Computing / Ph. D. (Information Systems)

The support and promotion of public Technical and Vocational Education and Training (TVET) Colleges is fundamental in addressing South Africa’s intermediate-level and artisanal skills as shortages in these areas contribute to considerable unemployment in South Africa. These institutions have been earmarked by the South African government for extensive growth. Therefore, efficient and effective management and accurate decision-making within these institutions are essential. The evaluation of the management information systems (MISs) within these institutions, which provide data and information to inform institutional short-term and long-term management decision-making and day-to-day operations, should take place on a regular basis to so enhance the reliability and accuracy of the data and information. The problem is that no evidence of a methodology (artefact) for the evaluation of MISs at public TVET Colleges in South Africa could be found in the literature. Therefore, the rationale for this study is to develop a methodology for the evaluation of MISs at public TVET Colleges in South Africa. Hence the main research question for the study was formulated as: What are the components that constitute a methodology for the evaluation of a MIS at a public TVET College in South Africa? The study was conducted according to a design science paradigm. Design science is underpinned by a pragmatic philosophical paradigm which considers thought as a tool for prediction, problem solving and action. The Design Science Research Process (DSRP) model informed the research process utilised to develop the artefact for this problem centred initiated study. The iterated activities of the DSRP model which include: design, demonstrate, evaluate and and communicate, contributed to the refinement of the methodology (artefact). The artefact mainly underwent experimental evaluation to demonstrate its applicability. The methodology (artefact) was empirically evaluated at three cluster-random selected public TVET Colleges after all colleges, with similar MIS maturity levels, were clustered into groups.The study contributed to the extant knowledge base of: theory building, on different levels. The main theoretical contribution is the final evaluated methodology (DSR artefact) which enables IT practitioners and MIS managers at public TVET Colleges in South Africa to evaluate their MISs on a regular basis. The methodology (artefact) presents a theory for design and action which satisfies the conditions of importance, parsimony and novelty on a micro-level. The study furthermore contributed to the extant literature on the theory of MIS success evaluation by contributing to theory on the measurement of MIS success constructs and measuring of the relationships between the constructs. Another theoretical contribution is the innovative evidence-based method by which the public TVET Colleges were clustered. The clustering method was used to ensure a more rigorous sample selection technique than purposive or convenient sample selection of cases and is generalisable to other knowledge domain contexts. The research study furthermore produced results of interest to both technology-focused and management-focused audiences. For technology-focused audiences the processes by which the artefact was constructed and evaluated are described, thus establishing repeatability of the study and building the knowledge base for further research extensions by future design science researchers. The rigour of the artefact design process was complemented by a thorough presentation of the experimental design of the artefact’s field test in three public TVET College environments which provides sufficient detail for management audiences to determine if sufficient organisational resources exist for utilisation of the artefact. / Information Science / Ph. D. (Information Systems)

The support and promotion of public Technical and Vocational Education and Training (TVET) Colleges is fundamental in addressing South Africa’s intermediate-level and artisanal skills as shortages in these areas contribute to considerable unemployment in South Africa. These institutions have been earmarked by the South African government for extensive growth. Therefore, efficient and effective management and accurate decision-making within these institutions are essential. The evaluation of the management information systems (MISs) within these institutions, which provide data and information to inform institutional short-term and long-term management decision-making and day-to-day operations, should take place on a regular basis to so enhance the reliability and accuracy of the data and information. The problem is that no evidence of a methodology (artefact) for the evaluation of MISs at public TVET Colleges in South Africa could be found in the literature. Therefore, the rationale for this study is to develop a methodology for the evaluation of MISs at public TVET Colleges in South Africa. Hence the main research question for the study was formulated as: What are the components that constitute a methodology for the evaluation of a MIS at a public TVET College in South Africa? The study was conducted according to a design science paradigm. Design science is underpinned by a pragmatic philosophical paradigm which considers thought as a tool for prediction, problem solving and action. The Design Science Research Process (DSRP) model informed the research process utilised to develop the artefact for this problem centred initiated study. The iterated activities of the DSRP model which include: design, demonstrate, evaluate and communicate, contributed to the refinement of the methodology (artefact). The artefact mainly underwent experimental evaluation to demonstrate its applicability. The methodology (artefact) was empirically evaluated at three cluster-random selected public TVET Colleges after all colleges, with similar MIS maturity levels, were clustered into groups. The study contributed to the extant knowledge base of: theory building, on different levels. The main theoretical contribution is the final evaluated methodology (DSR artefact) which enables IT practitioners and MIS managers at public TVET Colleges in South Africa to evaluate their MISs on a regular basis. The methodology (artefact) presents a theory for design and action which satisfies the conditions of importance, parsimony and novelty on a micro-level. The study furthermore contributed to the extant literature on the theory of MIS success evaluation by contributing to theory on the measurement of MIS success constructs and measuring of the relationships between the constructs. Another theoretical contribution is the innovative evidence-based method by which the public TVET Colleges were clustered. The clustering method was used to ensure a more rigorous sample selection technique than purposive or convenient sample selection of cases and is generalisable to other knowledge domain contexts. The research study furthermore produced results of interest to both technology-focused and management-focused audiences. For technology-focused audiences the processes by which the artefact was constructed and evaluated are described, thus establishing repeatability of the study and building the knowledge base for further research extensions by future design science researchers. The rigour of the artefact design process was complemented by a thorough presentation of the experimental design of the artefact’s field test in three public TVET College environments which provides sufficient detail for management audiences to determine if sufficient organisational resources exist for utilisation of the artefact. / Information Science / Ph. D. (Information Systems)

To create, update, or deploy a mobile application, a collection of hand-operated works must be satisfied. In this project, regardless of the mobile application's code and its core functionalities, which can be an e-book, an application, or even a mobile game, we will study how to automate, visualize and simplify the following manual procedures: 1.Create a remote Git repository for the mobile application. 2.Constructing or altering the mobile application's configuration or graphical contents. 3.Push all changes to the remote Git repository. 4.Deploy or distribute the mobile application from its Git repository after each push. / För att skapa, uppdatera eller distribuera en mobilapplikation måste en samling handstyrda verk uppfyllas. I detta projekt, oavsett mobilapplikationens kod och dess kärnfunktioner, som kan vara en e-bok, en applikation eller till och med ett mobilspel, kommer vi att studera hur man automatiserar, visualiserar och förenklar följande manuella procedurer: 1. Skapa ett avlägset Git -arkiv för mobilapplikationen. 2.Konstruera eller ändra mobilapplikationens konfiguration eller grafiska innehåll. 3.Push alla ändringar i det externa Git -arkivet. 4. Distribuera mobilappen från sitt Git -arkiv efter varje ändring.

PhD (Business Management) / Department of Business Management / This thesis demonstrates the researcher’s efforts to put into practice the theoretical foundations of information systems research, in order to come up with a context-aware business intelligence framework (CABIF), for the South African higher education institutions. Using critical realism as the philosophical underpinning and mixed methods research design, a business intelligence (BI) survey was deployed within the South African public higher education institutions to measure the respondents’ satisfaction and importance of business intelligence characteristics. The 258 respondents’ satisfaction and importance of the 34 observed business intelligence variables, were subjected to principal components analysis and design science research to come up with the CABIF. The observable BI variables were drawn from four latent variables namely technology and business alignment; organizational and behavioural strategies; business intelligence domain; and technology strategies. The study yielded good values for all the observed satisfaction and importance business intelligence variables as indicated by the Kaiser- Meyer-Olkin (KMO) Measure of Sampling Adequacy and the Bartlett Test of Sphericity. The data set collected from the survey deployed at the South African public higher education institutions, was reliable and valid based on the Cronbach α values which were all above 0.9. The researcher then used the descriptive and prescriptive knowledge of design science research, and the meta-inferences of the results from the principal components analysis to produce five contexts of CABIF. The BI contexts developed were, the Basic Context; the Business Processes Context which was divided into Macro and Micro business process contexts; the Business Intelligence Context; and the Governance Context. These contexts were extrapolated within the University of Venda’s business processes and this researcher concluded that the CABIF developed, could be inferred within the South African higher education institutions. At the University of Venda, this researcher managed to draw up CABIF based business intelligence tools that spanned from leveraging the existing ICT infrastructure, student cohort analysis, viability of academic entities, strategic enrolment planning and forecasting government block grants. The correlations and regression measures of the technology acceptance variables of the business intelligence tools modelled using CABIF at University of Venda, revealed high acceptance ratio. Overall, this research provides a myriad of conceptual and practical insights into how contextualised aspects of BI directly or indirectly impact on the quality of managerial decision making within various core business contexts of South African higher education institutions.

Im Fokus der Dissertation steht die Erforschung nachhaltiger Effekte durch Informationssysteme, insbesondere Ansatzpunkte zur Nachhaltigkeitstransformation der Gesellschaft durch Methoden und Artefakte der Green Information Systems (Green IS). Als Green IS werden sozio-technische Informationssysteme bezeichnet, die neben wirtschaftlichen Kriterien der ressourceneffizienten Bereitstellung von Informationen, der Koordination und Kommunikation auch die ökologische und soziale Dimension gemäß der „Triple Bottom Line“ (Drei-Säulen-Modell der nachhaltigen Entwicklung) adressieren. Der Anwendungsbereich von Green IS liegt auf der Reduktion von Umweltbelastungen und der Bewältigung komplexer Umweltherausforderungen durch sozio-technische Informationssysteme. Neben Forschungsthemen der (Wirtschafts-)Informatik und der Wirtschaftswissenschaften werden Bereiche der Psychologie und Sozialwissenschaften zu Fragen der digitalen Nachhaltigkeitstransformation, der Nachhaltigkeitsbewertung sowie Akzeptanzforschung behandelt. Aufgrund der Komplexität und Vielschichtigkeit des Themas wird ein multimethodischer Forschungsansatz verfolgt, indem sowohl qualitative als auch quantitative Methoden zum Einsatz kommen. Die zentralen Forschungsfragen lauten dabei wie folgt: FF1. Welchen Beitrag können Green IS auf Makro- und Meso-Ebene zur Nachhaltigkeitsbewertung leisten und welchen Reifegrad weisen sie auf? FF2. Inwiefern können digitale Geschäftsmodelle zur unternehmerischen und gesellschaftlichen Nachhaltigkeitstransformation beitragen? FF3. Kann durch gezieltes Nachhaltigkeitsmarketing die Akzeptanz von Green IS in der Gesellschaft gefördert werden? Gemäß der Design Science Research werden Verfahren zur Nachhaltigkeitsbewertung für Smart City Mobilitätsstrategien und betriebliche Umweltinformationssysteme (BUIS) des produzierenden Gewerbes konstruiert. Es wird ein Prototyp zum webbasierten Benchmark solcher Smart City Initiativen realisiert. Das entwickelte Geschäftsprozessmodell zeigt auf, inwiefern eine Transformation zur Plattformorganisation im Rahmen von Open Innovation für Industriebetriebe erfolgreich gelingen kann. Die quantitativen Erhebungen zeigen auf, das vor allem hochpreisige Informations- und Kommunikationstechnologie (IKT) für Geschäftsmodelle der Sharing Economy geeignet ist sowie, dass die Akzeptanz nachhaltiger IKT in der Gesellschaft bereits insbesondere bei Zugehörigen des "Lifestyle of Health and Sustainability" (LOHAS) vorhanden ist und der weiteren Förderung durch geeignete Verbraucher-Symbole bedarf.

Following the discovery of the one-dimensional sequence of human DNA, much focus has been directed on microscopy and molecular techniques to learn about the spatial organization of chromatin in a 3D cell. The development of these powerful tools has enabled high-resolution, genome-wide analysis of chromosome structure under many different conditions. In this thesis, I focus on how the organization of interphase chromatin is established and maintained following mitosis. Mitotic chromosomes are folded into helical loop arrays creating short and condensed chromosomes, while interphase chromosomes are decondensed and folded into a number of structures at different length scales ranging from loops between CTCF sites, enhancers and promoters to topologically associating domains (TADs), and larger compartments. While the chromatin organization at these two very different states is well defined, the transition from a mitotic to interphase chromatin state is not well understood. The aim of this thesis is to determine how interphase chromatin is organized following mitotic chromosome decondensation and to interrogate factors potentially responsible for driving the transition. First, I determine the temporal order with which CTCF-loops, TADs, and compartments reform as cells exit mitosis, revealing a unique structure at the anaphase-telophase transition never observed before. Second, I test the role of transcription in reformation of 3D chromosome structure and show that active transcription is not required for the formation of most interphase chromatin features; instead, I propose that transcription relies on the proper formation of these structures. Finally, I show that RNA in the interphase nucleus can be degraded with only slight consequences on the overall chromatin organization, suggesting that once interphase chromatin structures are achieved, the structures are stable and RNA is only required to reduce the mixing of active and inactive compartments. Together, these studies further our understanding of how interphase structures form, how these structures relate to functional activities of the interphase cell, and the stability of chromatin structures over time.

In dieser Arbeit werden Unternehmensnetzwerke aus einer abhängigkeitsbasierten Perspektive betrachtet und es wird ein Beitrag zum Management solcher Netzwerke geleistet. Unter dem Begriff Management wird im Kontext dieser Arbeit die ganzheitliche Planung, Kontrolle und Steuerung verstanden. Dabei wurden in sechs wissenschaftlichen Erst- und Koautorenschaften diverse gestaltungsorientierte Forschungsergebnisse in Form von Design-Science-Artefakten entwickelt. Mit deren Hilfe können Managementaktivitäten in den Bereichen Business-IT-Alignment, Partnerauswahl in Netzwerken, sowie IT-Governance auf der Basis von Abhängigkeiten mit interorganisationaler Ausprägung betrachtet und gemeistert werden. In dieser kumulativen Dissertationsschrift werden die Resultate entlang des Lebenszyklus von Unternehmensnetzwerken eingeordnet, wodurch die Relevanz der eingereichten Artikel auf die einzelnen Netzwerklebensphasen gespiegelt wird. Zudem werden sowohl theoretische als auch praktische Implikationen der Resultate diskutiert. Insgesamt tragen sowohl die ganzheitliche Sichtweise als auch der interdisziplinäre Charakter der Ausarbeitungen zu einem gesteigerten Verständnis von Abhängigkeitsbeziehungen in Unternehmensnetzwerken bei.

Indiana University-Purdue University Indianapolis (IUPUI) / Evolutionary testing (ET) techniques (e.g., mutation, crossover, and natural selection) have been applied successfully to many areas of software engineering, such as error/fault identification, data mining, and software cost estimation. Previous research has also applied ET techniques to performance testing. Its application to performance testing, however, only goes as far as finding the best and worst case, execution times. Although such performance testing is beneficial, it provides little insight into performance characteristics of complex functions with multiple branches. This thesis therefore provides two contributions towards performance testing of software systems. First, this thesis demonstrates how ET and genetic algorithms (GAs), which are search heuristic mechanisms for solving optimization problems using mutation, crossover, and natural selection, can be combined with a constraint solver to target specific paths in the software. Secondly, this thesis demonstrates how such an approach can identify local minima and maxima execution times, which can provide a more detailed characterization of software performance. The results from applying our approach to example software applications show that it is able to characterize different execution paths in relatively short amounts of time. This thesis also examines a modified exhaustive approach which can be plugged in when the constraint solver cannot properly provide the information needed to target specific paths.