Indiana University-Purdue University Indianapolis (IUPUI) / Friedreich’s Ataxia (FRDA) is a rare and poorly understood autosomal recessive disease caused by a pathological deficiency of the mitochondrial protein frataxin. Patients suffer neurodegeneration, ataxia, diabetes, and heart failure. In an effort to understand the mechanisms of heart failure in FRDA, we investigated the role of the protein modification acetylation, which is highly abundant on mitochondrial proteins and has been implicated in regulating intermediary metabolism. Using mouse models of FRDA, we found that cardiac frataxin deficiency causes progressive hyperacetylation of mitochondrial proteins which is correlated with loss of respiratory chain subunits and an altered mitochondrial redox state. Mitochondrial protein hyperacetylation could be reversed by the mitochondria-localized deacetylase SIRT3 in vitro, suggesting a defect in endogenous SIRT3 activity. Consistently, frataxin-deficient cardiac mitochondria showed significantly decreased rates of fatty acid oxidation and complete oxidation to carbon dioxide. However, the degree of protein hyperacetylation in FRDA could not be fully explained by SIRT3 loss. Our data suggested that intermediary metabolites and perhaps acetyl-CoA, which is required for protein acetylation, are accumulating in frataxin-deficient mitochondria. Upon testing the hypothesis that mitochondrial protein acetylation is non-enzymatic, we found that the minimal chemical conditions of the mitochondrial matrix are sufficient to cause widespread non-enzymatic protein acetylation in vitro. These data suggest that mitochondrial protein hyperacetylation in FRDA cardiomyopathy mediates progressive post-translational suppression of mitochondrial oxidative pathways which is caused by a combination of SIRT3 deficiency and, likely, an accumulation of unoxidized acetyl-CoA capable of initiating non-enzymatic protein acetylation. These findings provide novel insight into the mechanisms underlying a poorly understood and fatal cardiomyopathy and highlight a fundamental biochemical mechanism that had been previously overlooked in biological systems.

Due to the global energy crisis there is a vast increase in demand for heat exchangers that reduces the energy consumption during energy transfer between mediums. The current manufacturing process for brazed heat exchangers at the world leading man-ufacturer, Alfa Laval, involves a partial assembly process called Plastic Flange Defor-mation (PFD). The current PFD process is conducted manually and is completely dependent on human presence. The great increasing demand for heat exchangers world wide creates the need for a more efficient and sustainable solution for the PFD process. To meet the capacity increase a higher level of automated process is required. The key areas to investigate in this thesis are quality control and component handling within the PFD process. Concepts for the key areas will be developed and two new concepts for the automated PFD cell will be presented. The used method for this thesis is a combination of the outline of Design Research Methodology (DRM) and the Analytical Hierarchy Approach (AHP) for the decision making process for the final PFD cell concepts. The Developed key area concepts are validated with either physical prototypes or virtually with solid mechanics analysis. The result showed that there exist different solutions and possibilities for handling the large variety of components within the PFD process. The quality controls are solved with a combination of vision systems and actuator motors. The first concept for an automated PFD cell consists of two collaborative robots with specially designed grippers, that allow the robots to handle all the components and perform the quality controls. The cell contains specially designed racks for loading and unloading the pressure plates and frame plates. The second concept is a larger more complex solution with four industrial robots, and with a cycle time half as low as the first concept. Both cells contain the same developed key area concepts. The AHP suggests the second concept with respect to the weighting of the criteria from the stakeholders. The conclusion of this work is that there are opportunities to automate and improve the PFD process using robotics and automated quality controls. The presented concepts can help Alfa Laval meet the increasing demand for heat exchangers in an efficient and sustainable way. / På grund av den globala energikrisen ökar efterfrågan på värmeväxlare som minskar energiförbrukningen genom energiöverföring mellan medium. Alfa Laval är ett världsledande företag som bland annat tillverkar lödda värmeväxlare, där tillverkn-ingsprocessen för närvarande innefattar en delmonteringsprocess som kallas "Plastic Flange Deformation" (PFD). Den nuvarande PFD-processen utförs manuellt och är helt beroende av mänsklig närvaro. Den ökande efterfrågan på värmeväxlare skapar behovet av en mer effektiv och hållbar lösning för PFD-processen. För att möta kapacitetsökningen krävs en högre automatiseringsnivå. De viktigaste områdena att undersöka i denna avhandling är kvalitetskontroll och hantering av komponenter inom PFD-processen. Koncept för dessa områden kommer att utvecklas och två nya koncept för den automatiserade PFD-cellen kommer att presenteras. Metoden som används i denna avhandling är en kombination av Design Research Methodology (DRM) och Analytical Hierarchy Approach (AHP) för beslutsfattandet av de slutliga PFD-cell koncepten. De utvecklade koncepten för nyckelområdena valideras med fysiska prototyper eller virituellt genom hållfasthetsanalys. Resultaten visade att det finns olika lösningar och möjligheter för hantering av den stora variationen av komponenter inom PFD-processen. Kvalitetskontrollerna utförs med en kombination av visionsystem och aktuatorer. Det första konceptet för en automatiserad PFD-cell består av två kollaborativa robotar med speciellt utformade gripare som tillåter robotarna att hantera alla komponenter och utföra kvalitetskontroller. Cellen innehåller speciellt utformade stativ för lastning och avlastning av tryckplattor och stativplattor. Det andra konceptet är en större och mer komplex lösning med fyra industrirobotar och med en cykeltid som är häften så låg som det första konceptet. Båda cellerna innehåller samma utvecklade koncept för nyckelområdena. AHP föreslår det andra konceptet med hänsyn till viktningen av kriterierna från intressenterna. Slutsatsen av detta arbete är att det finns möjligheter att automatisera och förbättra PFD-processen med hjälp av robotteknik och automatiserade kvalitetskontroller. De presenterade koncepten kan hjälpa Alfa Laval att möta den ökande efterfrågan på värmeväxlare på ett effektivt och hållbart sätt.

This study focuses on the development of a validated and confirmed employee engagement measuring model for use by managers and academia. Data was collected from an array of South African managers by employing a structured 5-point Likert scale questionnaire. A total of 260 usable questionnaires could be analysed, signifying a high response rate of 80%. The Statistical Package for Social Sciences software (Version 18, Version 22.0 and AMOS for Windows) was used as the quantitative analytical software. The following statistical techniques were employed to analyse the data, namely the Kaiser-Meyer-Olkin measure of sampling adequacy, Bartlett‟s test of sphericity, Cronbach Alpha reliability coefficients, Exploratory factor analysis, Confirmatory factor analysis and the Pearson correlation coefficient. The development of the Measure Employee Engagement model wielded theoretical and empirical research. The format was structured into four logical stages, hence the presentation of the study in the approved article format. The study covers the following four steps (as per articles): Article one departed by performing a literature study of employee engagement constructs and its measuring criteria. It examined the application of a myriad of models in various application settings to identify the relevant constructs and measuring criteria. From these constructs and criteria, a draft questionnaire was constructed to collect the data on 11 employee engagement constructs. Validation of measuring criteria was performed to ensure that the criteria accurately measure the specific employee engagement construct. The data was also tested for acceptable reliability levels. The second article departs on the validation of the constructs and its measuring criteria, this time as a unified model and not, as performed in Article 1, the construct validation individually. The objective of this article was to simplify the complex model without deterioration of the measuring contribution thereof. This was achieved by employing factor analysis, and after four rounds of eliminating low-loading and dual-loading criteria, the questionnaire was reduced by 25 measuring criteria and seven factors were extracted explaining a favourable 69.75% of the variance. The simplified model was scrutinised to ascertain statistical validity thereof, an objective achieved with flying colours. The inter-correlations between the seven factors were satisfactory, underpinning the validity of the model. The third article focuses on confirming the employee engagement constructs statistically by means of Confirmatory Factor Analysis as well as to determine the goodness of the model fit. The results confirmed that all seven constructs were significant (p<0.05) and important according to the standardised regression weights. Surprisingly, the most important respondent construct Behavioural engagement had the lowest regression weight, while the lower rated Career growth opportunities showed a much higher regression weight – signifying a higher importance and influence on employee engagement. Regarding goodness of model fit, the CFI, RMSEA and Hoelter‟s indices‟ were used. These indices showed that the model as stated above to measure employee engagement is a good fit and that it can be operationalised to be employed in managerial application settings. Article four operationalised the model validated in Articles 2 and 3. The article thus reports on the actual measurement of the different employee engagement constructs as perceived by the respondents. The results showed that the respondents regarded all seven the constructs as important, with Behavioural employment being regarded as the most important one. Career growth opportunities, surprisingly, was rated the least important construct of employee engagement. Correlational analysis indicated that no significant correlation coefficients exist between the demographic variables and the constructs of employee engagement. The study consisted of both a literature study as well as an empirical study. The university libraries of the North-West University and Management College of South Africa‟s Business School were used to source reference materials with the aid of a specialised research librarian at the North-West University to assist in the location of the most appropriate sources. Apart from the conclusions based on the results obtained in model development, generalised conclusions include the development of a successful model development methodology and guidance in the use of a number of the statistical techniques. This could greatly assist future researchers in the design of their studies, even outside the discipline of employee engagement. / PhD (Business Administration), North-West University, Potchefstroom Campus, 2015

This study focuses on the development of a validated and confirmed employee engagement measuring model for use by managers and academia. Data was collected from an array of South African managers by employing a structured 5-point Likert scale questionnaire. A total of 260 usable questionnaires could be analysed, signifying a high response rate of 80%. The Statistical Package for Social Sciences software (Version 18, Version 22.0 and AMOS for Windows) was used as the quantitative analytical software. The following statistical techniques were employed to analyse the data, namely the Kaiser-Meyer-Olkin measure of sampling adequacy, Bartlett‟s test of sphericity, Cronbach Alpha reliability coefficients, Exploratory factor analysis, Confirmatory factor analysis and the Pearson correlation coefficient. The development of the Measure Employee Engagement model wielded theoretical and empirical research. The format was structured into four logical stages, hence the presentation of the study in the approved article format. The study covers the following four steps (as per articles): Article one departed by performing a literature study of employee engagement constructs and its measuring criteria. It examined the application of a myriad of models in various application settings to identify the relevant constructs and measuring criteria. From these constructs and criteria, a draft questionnaire was constructed to collect the data on 11 employee engagement constructs. Validation of measuring criteria was performed to ensure that the criteria accurately measure the specific employee engagement construct. The data was also tested for acceptable reliability levels. The second article departs on the validation of the constructs and its measuring criteria, this time as a unified model and not, as performed in Article 1, the construct validation individually. The objective of this article was to simplify the complex model without deterioration of the measuring contribution thereof. This was achieved by employing factor analysis, and after four rounds of eliminating low-loading and dual-loading criteria, the questionnaire was reduced by 25 measuring criteria and seven factors were extracted explaining a favourable 69.75% of the variance. The simplified model was scrutinised to ascertain statistical validity thereof, an objective achieved with flying colours. The inter-correlations between the seven factors were satisfactory, underpinning the validity of the model. The third article focuses on confirming the employee engagement constructs statistically by means of Confirmatory Factor Analysis as well as to determine the goodness of the model fit. The results confirmed that all seven constructs were significant (p<0.05) and important according to the standardised regression weights. Surprisingly, the most important respondent construct Behavioural engagement had the lowest regression weight, while the lower rated Career growth opportunities showed a much higher regression weight – signifying a higher importance and influence on employee engagement. Regarding goodness of model fit, the CFI, RMSEA and Hoelter‟s indices‟ were used. These indices showed that the model as stated above to measure employee engagement is a good fit and that it can be operationalised to be employed in managerial application settings. Article four operationalised the model validated in Articles 2 and 3. The article thus reports on the actual measurement of the different employee engagement constructs as perceived by the respondents. The results showed that the respondents regarded all seven the constructs as important, with Behavioural employment being regarded as the most important one. Career growth opportunities, surprisingly, was rated the least important construct of employee engagement. Correlational analysis indicated that no significant correlation coefficients exist between the demographic variables and the constructs of employee engagement. The study consisted of both a literature study as well as an empirical study. The university libraries of the North-West University and Management College of South Africa‟s Business School were used to source reference materials with the aid of a specialised research librarian at the North-West University to assist in the location of the most appropriate sources. Apart from the conclusions based on the results obtained in model development, generalised conclusions include the development of a successful model development methodology and guidance in the use of a number of the statistical techniques. This could greatly assist future researchers in the design of their studies, even outside the discipline of employee engagement. / PhD (Business Administration), North-West University, Potchefstroom Campus, 2015

The dissertation provides a consideration of the significance of choosing an appropriate post-graduate research methodology and application in higher education institutions. Research education has become a matter of concern as there are low completion rates of masters' students in South African universities. This study addresses the issue with the application of appropriate IS research methodologies of IT/IS masters' and MBA dissertations/theses at the NWU to determine whether the research approaches used in both disciplines were relevant to their studies. The choice of an appropriate research methodology is an arduous task with which many researchers are confronted during the research process. The problem is that IT/IS masters' and MBA students use particular research methodologies inappropriately but consider these to be the most appropriate methodologies for IS research for purposes of writing their dissertations. The primary research objective was to explore IT/IS and MBA students' ideological approach towards comprehending information and understanding dissertation requirements by preparing them to undertake sound research projects that culminate in masters' dissertations and improve research completion rates. Secondarily, it attempts to investigate the associated roles between students and supervisors, and to identify challenges encountered, specifically with IT MBA students that will force them to use particular research methods in their research dissertations. A quantitative research approach was adopted and a structured framework was used as an instrument for data-gathering. This structured framework was used randomly on all IT/IS masters' and MBA dissertations in the NWU library. The majority of IT/IS masters' dissertations were sourced through the Nexus Database to ensure a better return rate. The finding gathered from the use of a structured framework for purposes of investigating IT/IS masters' and MBA dissertations indicated that both disciplines, most especially the MBA dissertations, lack a conceptual matrix for research alignment, supervision guidance, and badly-structured research dissertations. There is a need for a graduate school and IT/IS department to introduce and encourage the use of an appropriate conceptual matrix underlying various research activities. / Thesis (M.Computer Sc & Information Systems) North-West University, Mafikeng Campus, 2014

After nine years of working in the field of social work, this including counselling, training and supervision, the researcher became aware of the need to develop a tool by which social workers could identify how they work. This study is for the social workers. It will review theory and techniques and then will go one step further. It will offer a new product to the social worker, a product whereby he or she can internally reflect on, investigate, argue about, integrate and finally, within the relationship the social worker has with his or her own working self, developed a personal practice model. Developmental research was selected as the research design. The tool to achieve the goal of developing a personal practice model was a workshop. A pilot study was undertaken at Family Life Centre. / Social Work / M.A. (Social Science (Mental Health))

Dissertation submitted in partial compliance with the requirements for a Masters Degree in Technology: Chiropractic, Durban University of Technology, 2010. / Background: The aim of this study was to determine the attitudes of Chiropractic students towards research at Durban University of Technology (DUT). The Chiropractic profession has made significant progress with regard to the production of high quality and clinically relevant research (Newell and Cunliffe, 2003; Hawk et al, 2008) and the continuation of this research effort will be the responsibility of the graduates that constitute the future profession (Newell and Cunliffe, 2003). Furthermore Cull, Yudkowsky, Schonfeld, Berkowitz and Pan (2003) state that the greatest predictor of this is a positive attitude, therefore it is essential to establish the present attitudes amongst the students. Method: The study was a quantitative questionnaire based, self administered, attitudinal survey. The sample group included all the Chiropractic students registered at DUT (n=185). Results: There was a response rate of 74,59%. The results indicated that on average students thought that the research subjects and courses taught at DUT were not interesting and that they did not adequately prepare them to perform research. The majority of the students felt that the research process was completely vague to them and that they felt insecure about their knowledge of research methodology. It was evident that students thought that DUT staff members placed a great emphasis on research and that they were easy to approach with regards to research. The area of greatest concern was that although students thought that the student researcher relationship was of great importance, they indicated that it was difficult to find a supervisor and they also indicated that inadequate supervision had delayed their research progression. For the most part students thought that research was important and they enjoyed listening to and reading research. However, only slightly positive scores were recorded when students were asked if they wanted to do research in the future, as they felt it was difficult and time consuming. Conclusion: Many factors were significantly associated with positive attitudes towards research at DUT and the strongest correlation between scales was between the importance of research and positive feelings towards research (r=0.713). Most students felt research was important and that it made them more knowledgeable however, if given the choice they would study at an institute where research was not mandatory. / Durban University of Technology

Thesis (MA)--Stellenbosch University, 2004. / ENGLISH ABSTRACT: Treatment outcome research strives towards objective estimates of disorder-specific treatment efficacy and has been applied to most psychiatric disorders. However, due to shortcomings in outcome research designs, problems still remain regarding the interpretation and generalisability of treatment outcomes. This is despite the development of research methodology criteria such as the Gold Standards, currently viewed as essential criteria for well-controlled cognitive-behavioural outcome research. The objectives of this assignment are (a) to assess the Gold Standards as criteria for treatment outcome research by means of a qualitative overview and evaluation of exposure treatment studies for PTSD, and (b) to make recommendations for the expansion and/or modification of these criteria. An assessment of five selected treatment outcome trials, based on the Gold Standards, showed significant limitations in the scope of the Gold Standards regarding (a) the inclusion of target symptoms in the research hypotheses, (b) estimates of treatment adherence, (c) guidelines for statistical analyses of attrition points, (d) the ethical implementation of exposure treatment, and (e) estimates of significant clinical change. It is concluded that the Gold Standards are not sufficient to ensure valid and reliable treatment outcomes. Recommendations are made for the expansion of four of the existing Gold Standards parameters and three additional criteria are proposed. Key words: treatment outcome research, Gold Standards, post-traumatic stress disorder, exposure therapy. / AFRIKAANSE OPSOMMING: Navorsing oor behandelingsuitkoms streef na objektiewe resultate oor die uitkoms van behandeling vir spesifieke psigiatriese versteurings. Nogtans, weens tekortkominge in die ontwerp van uitkomsstudies, word talle probleme steeds ervaar met die interpretasie en veralgemeenbaarheid van die resultate van die studies. Dit is die geval ten spyte van die ontwikkeling van navorsingskriteria soos die "Gold Standards" wat huidig as die belangrikste kriteria vir uitkomsstudies op die gebied van die kognitiewe gedragsterapie aanvaar word. Hierdie projek het ten doelom (a) die Gold Standards as kriteria vir uitkomsnavorsing te assesseer deur middel van 'n kwalitatiewe oorsig en evaluering van vyf geselekteerde uitkomsstudies van blootstellingsterapie vir post-traumatiese stresversteuring, en (b) om aanbevelings te maak ter aanvulling enJofwysiging van die Gold Standards. Evaluasie van die studies het betekenisvolle beperkings in die Gold Standards se omvattenheid uitgelig in terme van (a) die insluiting van teikensimptome in die navorsingshipoteses, (b) die skatting van behandelingvoitrekking ("treatment adherence"), (c) riglyne vir die statistiese analise van data oor attrisie, (d) die etiese implementering van blootstellingsterapie, en (e) skattings van betekenisvolle kliniese verandering. Dit blyk dat die Gold Standards nie voldoende is om geldige en betroubare resultate oor behandelingsuitkomste te verseker nie. Aanbevelings word gemaak vir die hersiening van vier van die Gold Standards kriteria en drie addisionele kriteria word voorgestel. Sleutelwoorde: behandelingsuitkomsnavorsing. Gold Standards, post-traumatiese stresversteuring, blootstellingsterapie.

The software engineering community is concerned with improvements in existing methods and development of new and better methods. The research approaches applied to take on this challenge have hitherto focused heavily on the formal and specifying aspect of the method. This has been done for good reasons, because formalizations are the means in software projects to predict, plan, and regulate the development efforts. As formalizations have been successfully developed new challenges have been recognized. The human and social role in software development has been identified as the next area that needs to be addressed. Organizational problems need to be solved if continued progress is to be made in the field. The social element is today a little explored area in software engineering. Following with the increased interest in the social element it has been identified a need of new research approaches suitable for the study of human behaviour. The one sided focus on formalizations has had the consequence that concepts and explanation models available in the community are one sided related in method discourses. Definition of method is little explored in the software engineering community. In relation to identified definitions of method the social appears to blurring. Today the software engineering community lacks powerful concepts and explanation models explaining the social element. This thesis approaches the understanding of the social element in software engineering by applying ethnomethodologically informed ethnography and ethnography. It is demonstrated how the ethnographic inquiry contributes to software engineering. Ethnography is also combined with an industrial cooperative method development approach. The results presented demonstrate how industrial external and internal socio political contingencies both hindered a method implementation, as well as solved what the method was targeted to do. It is also presented how project members’ method deployment - as a social achievement is played out in practice. In relation to this latter contribution it is provided a conceptual apparatus and explanation model borrowed from social science, The Documentary method of interpretation. This model addresses core features in the social element from a natural language point of view that is of importance in method engineering. This model provides a coherent complement to an existing method definition emphasizing formalizations. This explanation model has also constituted the underpinning in research methodology that made possible the concrete study results.

published_or_final_version / abstract / Social Sciences / Doctoral / Doctor of Philosophy