Growth suppression mediated by connexin 37 (Cx37; also known as GJA4) requires interaction between its C-terminus and functional pore-forming domain. Using rat insulinoma cells, we show that Cx37 induces cell death and cell cycle arrest, and slowed cell cycling. Whether differential phosphorylation might regulate intramolecular interactions, and consequently the growth-suppressive phenotype, is unknown. Protein kinase C inhibition increased the open state probability of low-conductance gap junction channels (GJChs) and reduced GJCh closed state probability. Substituting alanine at serine residues 275, 302 and 328 eliminated Cx37-induced cell death, supported proliferation and reduced the GJCh closed state probability. With additional alanine for serine substitutions at residues 285, 319, 321 and 325, Cx37-induced cell death was eliminated and the growth arrest period prolonged, and GJCh closed state probability was restored. With aspartate substitution at these seven sites, apoptosis was induced and the open state probability of large conductance GJChs (and hemichannels) was increased. These data suggest that differential phosphorylation of the C-terminus regulates channel conformation and, thereby, cell cycle progression and cell survival.

Magister Curationis - MCur / Background: Nursing as a profession is based on firm knowledge, values, clinical skills and attitudes. In the current dynamic healthcare systems, all nurses are challenged to be insightful and have robust clinical reasoning and psychomotor skills in order to integrate theory into practice. Therefore, they need to be accountable in ensuring that they perform optimally to meet the extensive demands of clinical settings. Theory-practice integration is a major element that sustains quality and drives best nursing practice. One of the barriers to theory-practice integration is the gap between theory and practice in nursing education. Therefore, if sound theory is the basis for understanding the reality of the clinical setting, then every effort should be made to reduce the gap between theory and practice. Aim: The aim of the study was to explore and describe the challenges experienced by second and third-year nursing students when integrating theory into practice in a selected clinical setting in the Western Cape. Method: A qualitative approach, using an explorative, descriptive and contextual design, was employed. The target population of the study was the second and third-year nursing students who were registered for the Bachelor of Nursing Degree in the academic year of 2016. The selected non probability sample comprised of 14 participants. Data were collected using semi-structured focus group interviews, with an interview guide and probing to gain detailed information during the process of data collection. Interviews were audio recorded to ensure that no information would be lost and the researcher could review it when necessary. The content analysis method was used to analyse the data. Permission to conduct the study using the nursing students was obtained from the registrar of the University of the Western Cape and the HOD of Son. The research ethics committee granted ethics approval related to the study. All participants were involved in the study on a voluntary basis. Informed consent and focus group confidentiality binding forms were completed by participants to ensure confidentiality. Results: Four themes emerged from the findings namely: Theory verses practice, lack of role models, inadequate support structures and communication. The study highlighted that nursing students still experience a challenge with integrating theory into practice in the clinical settings. In addition the study highlighted that clinical guidance from the preceptors a crucial role in the professional development of students. The results of the study also showed that a new structure of facilitating nursing students in clinical settings must be in place. This structure should include proper orientation and supervision of the nursing students. The preceptors who facilitate clinical guidance must be equipped with the necessary knowledge and skills to ensure that they are able to facilitate and monitor the competence of the nursing students. Conclusion: Clinical nursing education is vital and indispensable in nursing education. It is very complex consisting of many aspects and situations, which can be challenging and demanding for a nursing student. Due to its complexity, it is essential for nursing students to be exposed to a variety of real life situations within their training in order to better prepare them for quality practice. Nursing students therefore require sufficient support from the clinical preceptor and the nursing educators, to acquire the necessary skills, knowledge and attitude to perform nursing duties with competence, when placed in the clinical settings. This calls a lot of attention from the higher learning institutions and the clinical settings to have standardised goals and expectation for the students, providing quality clinical accompaniment that will socialise the nursing student optimally in the profession and attempt to bridge the gap between theory and practice.

Training is often delivered before training needs analyses were completed for affected employees. The overall purpose of the study was to identify gaps in the perceived training needs between managers and employees. The first gap found that managers differ in how they perceived employees’ training needs. The second gap was found amongst employees about their own training needs. The managers responded through an electronic questionnaire and a conference, while employees completed their questionnaires at their business premises. The unique approach to this study lies in the fact that the employees were involved in the research while it is more common only to allow managers to complete questionnaires. Globally there is a shortage of supply chain management skills. Following the 2008 global recession, well-trained staff could allow businesses to recover economically. However the literature revealed that a lack of existing qualifications rendered employees vulnerable to lay-offs. For decades, governments, businesses and tertiary institutions have been mismatched in meeting their existing/future skills requirements. The research outcomes could help to prevent wasting resources required to train employees. The goal was accomplished by testing nine hypotheses against empirical evidence gathered in supply chain industries. The findings confirmed that managers and employees do not always share the same perceptions. Hypotheses testing on the following variables: the types of training, the format of training, motivating/demotivating variables for attending training, revealed differences. Other variables include respondents’ existing educational qualifications, their gender, age and career tenure. The respondents were questioned about signing contracts before being sent on training programs. This thesis reported and analysed the findings of three questionnaires. The study was in-field for four months in 2011. By using supply chain professional associations to target respondents the study yielded a more credible reflection of industry phenomena. The research contribution lies in the fact that it is a multi-disciplinary study trying to identify whether gaps exist in perceived training needs amongst respondents and why. It integrates theory from the disciplines of human resources, training and businesses management in structured supply chain networks. Future training programs can thus be tailored towards meeting actual employee training needs to align organisational with personal objectives. This study can help alleviate the skills shortage by emphasizing training needs analyses before the commencement of training programs. / Thesis (DCom)--University of Pretoria, 2014. / gm2014 / Business Management / unrestricted

Water resources managers are required to develop comprehensive water resource plans based on severely uncertain information of the effects of climate change on local hydrology and future socio-economic changes to localised demand. In England and Wales, current water resource planning methodologies include a headroom estimation process separate from water resources simulation modelling. This process quantifies uncertainty based on only one point of an assumed range of deviations from the expected climate and projected demand 25 years into the future. The research presented herein addresses this problem by developing an integrated the Water Resources Planning Robustness Assessment (WRP-RA) method based on Information-Gap Decision Theory (IGDT) to quantitatively assess the robustness of various supply side and demand side management options over a broad range of plausible futures. Findings show that beyond the uncertainty range explored with the headroom method, a preference reversal can occur, i.e. some management strategies that underperform at lower uncertainties, outperform at higher levels of uncertainty. Also, some management strategies that perform relatively well within the headroom range of uncertainty, fail just beyond this range. Additionally, this thesis demonstrates that when 50% or more of the population adopts demand side management in the form of efficiency related measures and/or innovative options such as rainwater collection and/or greywater reuse, the robustness of a management strategy can be greatly improved as can its ability to recover after a drought episode. The use of Multi-Criteria Decision Analysis shifts the focus away from reservoir expansion options and large-scale river abstractions that perform best in regards to water availability, to strategies that include innovative demand side management actions of rainwater collection and greywater reuse as well efficiency measures along with more traditional supply-side schemes. Therefore, this thesis illustrates how the WRP-RA can offer a comprehensive picture of the relative robustness of management strategies to more extreme supply/demand futures. The knowledge of which options and collections of options perform better in response to higher demands and lower supplies offers insight into more secure long term investment strategies.

The objective of this essay is to investigate how attitudes towards equality between men and women affect the gender wage gap. The essay studies how positive and negative attitudes on gender equality affects the gender income gap. This study investigates this by using data of the mean yearly incomes from 290 municipalities in Sweden during the years 2000-2008. Additionally, using a survey conducted by the SOM-institute at the Gothenburg university to measure attitudes towards gender equality. The results indicate that positive attitudes towards gender equality had a decreasing effect on the gender wage gap. A conclusion from this essay is that a more egalitarian attitude contributes to a decrease in the existing gender wage gap.

Master of Science / Department of Biochemistry / Dolores J. Takemoto / The vertebrate lens relies on gap junction-mediated intercellular communication to maintain cellular homeostasis and lenticular transparency. Differentiation of cuboidal lens epithelial cells into cortical fiber cells involves the degradation of endogenous gap junction protein, connexin 43 (Cx43) and the up-regulation of connexin 46 (Cx46). Cx46 may also be involved in the hypoxia response in other tissues; a function that can possibly be attributed to unique phosphorylation sites at the cytoplasmic C-terminus. In this study, we have developed a mammalian (rabbit) lens epithelial cell (RLEC) culture model that overexpresses Cx46 to ascertain the role of Cx46 in differentiation and oxidative stress response. The cell line N/N1003A was stably transfected with a GFPCx46 plasmid construct, and analyzed for differentiation markers including endogenous gap junction protein isoforms (Cx43 and Cx50). Western blot analysis and visual observation determined that the stable overexpression of Cx46 (sCx46OE) induced the degradation of Cx43 and elicited morphological changes indicative of fiber cell elongation. Total RNA from RLEC culture was isolated and analyzed for mRNA levels using RT-PCR. Comparable levels of Cx43 transcript were present in wild type, transient Cx46OE (tCx46OE), and sCx46OE which suggests a post-transcriptional regulation of Cx43 degradation. Treatment of sCx46OE with proteasome inhibitors restored Cx43 protein levels, and scanning confocal microscopy supported our hypothesis that Cx43 is degraded in differentiating lens cells by way of a ubiquitinmediated proteasomal pathway. It is our conclusion that Cx46 has application in hypoxic conditioning and differentiation in addition to its conventional role as a gap junction protein.

Prof. S.H. von Solms

This study is concerned with understanding the impact of message framing in influencing choice within the sustainable consumption domain. Over-consumption has been proven to be a main cause of environmental degradation, and a shift to sustainable consumption practices is needed. Yet research has found that despite knowledge of environmental issues, and a supportive attitude, pro-environmental behaviour amongst consumers is lacking, with a key influence being the lack of personal utility found in the pro-environmental choice. This study attempts to contribute to narrowing the knowledge attitude practice gap in this domain, by using message framing to isolate the personal utility available in a sustainable choice, thereby influencing a pro-environmental outcome.A study was conducted to determine the main and interaction effects of various salient message frames (reference dependence, loss aversion and time sensitivity) on behavioural intention within sustainable consumption context. Environmental attitude was also tested to ascertain the interaction effect of this variable with the other independent variables and the resultant impact on the choice made. Variables were manipulated in a 2x2x2 factorial design. Results yielded the hypothesised significance of main effects for time sensitivity, but not for reference dependence or loss aversion. In addition no three way interaction for reference dependence by loss aversion by time sensitivity was found. No interaction was found between message frame and environmental attitude. Implications for social marketers engaged in the promotion of pro-environmental behaviours are discussed. Copyright / Dissertation (MBA)--University of Pretoria, 2011. / Gordon Institute of Business Science (GIBS) / unrestricted

Master of Science / Department of Electrical and Computer Engineering / Behrooz Mirafzal / The rise of Wide Band Gap (WBG) devices has brought excitement in the field of Power converters. The WBG based converter can operate at the very high frequency and temperature making them ideal to use in harsh environments. The commercialization of WBG devices such as SiC and GaN MOSFETs has made it interesting for power engineering professionals all over the world. The use of WBG devices capable of operating at high switching frequencies reduces the overall system size dramatically with added benefit of improved power quality at high temperature. The main goal of this thesis is to design and test an AC-DC converter based on a SiC power module. The designed rectifier can be considered an active rectifier equipped with a controller to constantly provide feedback for modification of switching signals to get the desired output voltage. The designed active rectifier converts the varying frequency input power supply into rectified DC voltage while keeping the power factor of the system to unity. This thesis covers elementary information on power supply design, switching schemes and design of the controller. System arrangement will provide more light on the use of Six Channel MOSFET Gate Driver from CREE with the overall experimental setup. The experimental analysis will summarize the behavior of the system where information on achieved rectification, effect on the line currents at the generator and concluding power factor representation is described.

L’autophagie est un processus de dégradation et de recyclage des composés cellulaires. Ce mécanisme est nécessaire que ce soit à l’état basal pour éliminer des agrégats protéiques ou des organites endommagés ou en condition de stress, tels que la carence nutritionnelle, l’hypoxie ou encore des traitements anticancéreux. De ce fait, l’autophagie est un processus essentiel à la survie ainsi qu’au maintien de l’homéostasie cellulaire. Connaître les joueurs et comprendre les mécanismes de régulation de l’autophagie sont donc importants. Les GTPases RABs sont des régulateurs importants de ce processus. Celles-ci agissent comme des interrupteurs moléculaires permettant d’exécuter rapidement des fonctions dans la cellule. Les RABs sont activées par des Guanine Nucleotide Exchange Factors (GEF) alors que les GTPase Activating Proteins (GAP) accélèrent la désactivation de la RAB. RAB21 est essentielle dans les étapes tardives de l’autophagie. En effet, RAB21 est activée par la carence nutritionnelle, via sa GEF MTMTR13, et permet le trafic d’une SNARE requise pour le flux autophagique. Lors d’une carence prolongée, l’activité de RAB21 diminue rapidement, suggérant ainsi le rôle d’une GAP dans cette régulation négative. Toutefois, aucune GAP pour RAB21 n’a été identifiée jusqu’à maintenant. Un criblage génétique chez la drosophile a permis d’identifier quelques candidats. Suite à des essais d’interactions protéiques, il s’est avéré que seule la GAP TBC1D25 interagissait avec RAB21. De plus, cette interaction est augmentée en fonction de la carence nutritionnelle. Des immunofluorescences par microscopie confocale ont révélé que l’interaction RAB21-TBC1D25 était située en partie au niveau des endosomes précoces. Par ailleurs, une activation prolongée de RAB5, située sur les endosomes précoces, inhibe l’interaction RAB21-TBC1D25. De plus amples expériences devront être réalisées afin d’expliquer ces résultats. Dans un autre ordre d’idée, RAB21 est surexprimée dans les cellules ayant un flux autophagique élevé ainsi que dans certaines tumeurs de cancer du côlon (données non publiées du laboratoire). L’expression de Tbc1d25 dans ces mêmes tumeurs ne semble pas augmentée, indiquant que TBC1D25 pourrait être un inhibiteur autophagique spécifique aux cellules ayant un flux autophagique élevé. À la lumière des résultats obtenus, TBC1D25 semble être une GAP pour RAB21 qui permet sa régulation négative suivant l’activation de l’autophagie induite par la carence nutritionnelle. / Abstract : Autophagy is defined as the lysosomal degradation and recycling of cellular constituents. At basal levels, autophagy eliminates protein aggregates or damaged organelles. In condition of stress, such as in condition of nutritional deficiency, hypoxia or cancer treatments, autophagy allow cells to adapt and survive. Therefore, autophagy is an essential system required for survival and maintenance of cellular homeostasis. It is thus essential to identify the cellular entities and mechanisms regulating this process. RAB GTPases were identified as master regulators of autophagy. These particular proteins act as molecular switches for the rapid execution of cellular responses. RABs are activated by Guanine Nucleotide Exchange Factors (GEF) whereas GTPase Activating Proteins (GAP) accelerates RAB deactivation. RAB21 is essential in the late stages of autophagy. Indeed, RAB21 is activated by nutritional deficiency, via its GEF MTMTR13, to allow trafficking of a SNARE required for autophagic flux. During starvation, RAB21 is deactivated which suggest that a GAP could negatively regulate RAB21 activity. However, to date no GAP for RAB21 has been identified. An eye modifier genetic screen in Drosophila was performed to identify potential RAB21 GAPs and some candidates were identified. As a result of this screen, the GAP TBC1D25 was identified as interacting with RAB21. Moreover, this interaction was increased by starvation. Proximity ligation assays revealed that the RAB21-TBC1D25 interaction partially localized at early endosomes. Moreover, prolonged activation of RAB5, located at early endosomes, inhibited RAB21-TBC1D25 interaction. Further experiments will be carried out to explain these results. With respect to the roles of autophagy in cancer, RAB21 was shown to be overexpressed in cells with high autophagic flux as well as in some colon cancer tumors. Importantly, the expression of Tbc1d25 in these same tumors does not appear to be increased, indicating that TBC1D25 could be an autophagic inhibitor specific to cells with a high autophagic flow. My work suggests that TBC1D25 could function as a GAP to negatively regulate RAB21 activity in condition of prolonged starvation.