Investigation of the apoptotic pathway in glioblastoma in the context of suicide gene therapy

Glioblastoma is a highly malignant, aggressive and most common primary brain tumor in adults. Tremendous research efforts have been conducted in the field of GBM treatment discovery and succcess has only been achieved at pre-clinical level. Despite numerous approaches used in the treatment of GBM, patients still experience tumor progression, show extremely poor prognosis, high mortality and barely 12-15 months of median survival. To a certain extent, the failure of current treatment modalities to provide durable responses is due to tumor heterogeneity, a hostile tumor microenvironment and the tumor’s unique ability to evade the host’s immune system. Suicide gene therapy strategies are among the ongoing clinical studies for the treatment of GBM. Previous work from our lab shows that treatment of CT2A and GL261 mouse glioma cell lines with HSV-TK GCV SGT induced the apoptotic mechanism of cell death. Apoptosis is known to be non-immunogenic, hence it does not stimulate antitumor immune responses. Therefore, in this study we aimed to block the apoptotic pathway and study potential activation of alternative cell death pathways following HSV-TK/GCV induced SGT, which could be more immunogenic. To achieve our aims, we blocked the apoptotic pathway by knocking out two crucial genes in the apoptotic pathway (gene x and y; due to patenting conflicts, the names are not revealed) by CRISPR/Cas9 technology. Thereafter, investigations were conducted to study potential activation of lytic mode(s) of cell death, which are known to be more immunogenic. Our results demonstrate that CRISPR/Cas9 effectively knocks out our genes of interest. Due to limited time, further studies could not be conducted using gene y KO cells. Further experiments conducted using gene x KO cells reveal effective inhibition of the apoptotic pathway with delay in cell death in both cell models. We found that apoptosis was not the dominant mode of cell death in both KO cell lines and, no enhanced lytic cell death was observed in both KO cell lines. However, in GL261 KO cells, our findings suggested possible activation of another mode of cell death which needs to be categorized in the future. We recommend further investigations to be conducted to understand mechanisms involved in this mode of cell deathMaster's Thesis in Biomedical SciencesBMED395MAMD-MEDB

Complexities of accessing finance from government institutions and its agencies

Purpose: with the recent establishment of Small Business Development department, the ministry is tasked and will be responsible for ensuring that the business environment is enabling for new Small to Medium businesses. The real issue and the point of interest in researching this particular dissertation is the available literature around the issue of the SME sector which indicates that new SMEs in South Africa do not move from the first stage (existence) to other stages such as survival, success, take off and resource maturity. The study seeks to inaugurate two specific challenges (difficulties in accessing finance and to examine if there is sufficient non-financial SME incubators and mentorship programs post funding allocation). The area of study focused on SMEs that are concentrated in highly populated areas of Gauteng. Methodology: The study was conducted using qualitative research and a questionnaire was used as a data collection tool. The researcher was able to get valuable information on stakeholders in the SMME sector. This was done through the use of questionnaires to businesses, government funders and incubators. Results: when posed with a question of the start-up capital, a mere 17% responded to having obtained financial assistance from government institutions, 20% from friends and family while a massive 60% indicated they have used own capital to start businesses. When the researcher posed the question of the reasons that often leads to failure, approximately 23% of businesses mentioned lack of working equipment as the core reasons for the business failure while 17% indicated that lack of business opportunities or rather contracts of supply from government departments as the main impeding factor which resulted to failure. In terms of the availability of incubators, approximately 67% of respondents indicated that there were no business incubators available in their areas of business. Approximately 57% of businesses mentioned the inability to obtain loans from government funding institutions was the major business constraint that often leads to failure. The researcher posed a question to business incubators personnel that participated in the study to gain perspective as to why do they think SMEs fail within the first year of operation. Approximately 40% of respondents alluded that, barriers to entry by big corporates in South Africa force Small and Medium Enterprises out of businesses. Other participants added that the South African government procurement system does not provide opportunities to small businesses due to lack of experience. All government funding institutions participants mentioned that in most cases SMEs finance applications are rejected due to the fact that businesses fail to present viable business proposals that show the ability for business to remain operating for a long time Implications: The above analysed study findings indicate that there is a huge gap between small businesses and government funding institutions in terms of the awareness of the available financial support to SMEs. From the government perspective, it was indicated that businesses submit business plans that are not viable. There needs to be the middle ground where business plans compilation support currently provided by SEDA awareness should be spread across SMEs operating in the highly populated areas of Gauteng. Recommendations: Access to finance is a major constraint hindering the growth and success of small enterprises. The South African government has established a number of financial support programmes aimed to assist SMEs. With these financial support programmes, most of the SMEs are unsuccessful due to the fact that they cannot easily access those funds and as a result they remain stagnant for a very long time or end up shutting down. Conclusion: The effect of credit rationing is the potential loss of opportunity and or reduction in the scale of a business, neither of which is a desirable outcome. At the most fundamental level, there are lost opportunities for the borrower and the lender. There are implications for the wider economy also. SMEs are a key source of innovation, competition and choice

Crime scene investigators: exploring the reasons and impact of career longevity and gender diversity in forensic science

Career longevity among crime scene investigators (CSIs) is a topic for which there has been little research. This is surprising given the increased popularity of this profession as well as forensic science in general. Understanding the profession and the career dynamics of those who serve as CSIs can provide valuable insight which can be used to improve efficiency and effectiveness on the job and promote lengthy and successful careers. This study examines the career longevity of female versus male crime scene investigators and identifies the key reasons behind early departures from the field. The study looks at career inspirations, expectations, and professional pathways for both male and female forensic science students and those already working as career CSIs. Two similar surveys were sent out, one to currently working, and retired crime scene investigators and/or death scene investigators, and one to forensic science students at the University of Central Oklahoma. The sample pool included 45 survey responses from current and former professionals in the field, and 57 responses from forensic science students. From the surveys that were received, we discovered that female crime scene investigators are more likely to leave the profession early than their male counterparts. We identified the various reasons why this was so and formulated suggestions for addressing these issues. We also discovered that the main incentive for students to choose forensic science was because they thought it was an interesting career and they wanted to serve the community in a unique manner, however some apparently did not think beyond this to the demands of the job and the effect it would have on lifestyle and family. From this result, we concluded female CSIs tend to quit the profession early more than their male counterparts and that there are articulable reasons which could be better addressed

Taxonomic revision of the Memecylon natalense species-complex in southern Africa.

Masters Degree. University of KwaZulu-Natal, Durban.iv ABSTRACT Two Memecylon species (M. natalense and M. bachmannii) were previously recognized in southern Africa, and three species of M. section Buxifolia as occurring in Mozambique (M. natalense, M. torrei and M. insulare). However, a recent nrDNA phylogeny revealed that M. natalense as previously circumscribed is not a monophyletic group and includes some geographically outlying populations warranting recognition as distinct evolutionary lineages. In this dissertation, I present the results of a comprehensive morphological study and revision of the ‘M. natalense species-complex’ including the following taxa: M. natalense sensu stricto (endemic to South Africa in KwaZulu-Natal, Eastern Cape, Mpumalanga and Limpopo), M. incisilobum (southern Mozambique), M. nubigenum (southern Malawi), M. rovumense (southeastern Tanzania), M. aenigmaticum (northern Mozambique), M. sp. nov. 1 (northeastern Kwazulu-Natal, South Africa), M. sp. nov. 2 (Eastern Cape province, South Africa), and M. sp. nov. 3 (Limpopo province, South Africa). Although M. bachmannii (Eastern Cape and KwaZulu-Natal) is morphologically distinct, it was also included in the present study because of recent nrDNA work indicating a close relationship with M. natalense. Species boundaries were investigated using phenetic and cladistic methods based on morphology. Phenetic analysis using the Unweighted Pair Group Method with Arithmetic Mean (UPGMA) revealed that M. bachmannii clustered independently, M. sp. nov. 1 clustered close to M. incisilobum, M. aenigmaticum clustered close to M. rovumense, and M. nubigenum clustered close to a subcluster consisting of M. natalense, M. sp. nov. 2 and M. sp. nov. 3. The morphological cladistic results were congruent with a previous molecular analysis in that M. sect. Buxifolia was monophyletic. Memecylon rovumense + M. aenigmaticum and M. incisilobum + M. sp. nov. 1 appeared in separate clades. Memecylon bachmannii and M. nubigenum were each monophyletic, while M. natalense, M. sp. nov. 2 and M. sp. nov. 3 appeared in an unresolved polytomy. Overall, the cladistic results were in agreement with the UPGMA analysis but were less resolved. Vegetative and fruit morphology have proven to be of great diagnostic value in delimiting the members of the M. natalense species-complex. Four new species have been named and described, while a further three new species are proposed. Dichotomous keys are provided, and the conservation status of each species is assessed according to the criteria of the IUCN. A lectotype should be designated for M. natalense. With these additions, the flora of Mozambique now has seven species of Memecylon (including six species in M. sect. Buxifolia). In South Africa, the number of recognized Memecylon species has increased from two to five

Teachers’ and Administrator’s Perceptions and Concerns of Reciprocal Peer Review Program

This study examined a pilot Reciprocal Peer Review Program (RPRP) that was implemented for 1 year by a mid-size suburban school district in Minnesota. In the RPRP two teachers were paired up for the purpose of observing each other and “exchanging feedback in an alternating fashion” (Kohler, Ezell, & Paluselli, 1999, p. 154). The study reviewed the pilot program to determine teachers’ and administrator’s perceptions and concerns of the program. The study also sought to determine features of the pilot program that participants considered to be effective and worth keeping and features of the program that were considered not effective thus needed to be refined or discarded. The study was designed to provide insights into the implementation of the Reciprocal Peer Review Program (RPRP) in a medium size suburban school district in Minnesota. The information provided by the study was used by the school district and teachers to determine whether or not there is merit in pursuing full implementation of the RPRP throughout the district with all teachers. The study provided specific commendation on features of the RPRP that were considered effective. Additionally, the study provided recommendations of features of the RPRP that were viewed negatively and required change. Although the study is limited to a single Minnesota school district, it is conceivable that other state school districts, also required to implement the new the new teacher evaluation statute that mandates peer review, will find value in the analysis of the design and implementation of a quality peer review program. The researcher collected both qualitative and quantitative data from a select sample of 60 teachers who volunteered to participate in the RPRP and from three school district administrators who participated in designing and implementing the RPRP. Four instruments were used in the study data collection for the study: (1) Stages of Concern Questionnaires (SoCQ); (2) Perception Survey; (3) focus group interview with seven teachers; and (4) focus interview with three school administrators. The quantitative data were electronically collected and analyzed. Focus group interviews were digitally audio-recorded, transcribed, and thematically. The study found that teachers and administrators had general positive perceptions of the RPR program with the following features particularly reported as positive: opportunity to observe; opportunity to learn and collaborate with colleagues; the non-evaluative nature of the program, and the opportunity to study curriculum across content and grade levels. Also, teachers thought that the program helped improve instruction and reduce teacher isolation. The results indicated that participants viewed the following as areas of concern: lack of clarity on goals and procedures; limited time; too much or confusing paperwork demands; poor substitute teacher system; and level of district and state commitment to funding the program. Participants pointed out the following as recommendations for improving the program: improve the school culture around the importance of RPRP; provide more administrative support to teachers; provide more clarifications of goals and procedures; provide more training on RPRP; improve the teacher substitute system; and allow teachers to use the Professional Learning Community (PLC) time for peer review or consider paying teachers stipends for time spent working on the program outside contract hours. Since the RPRP was viewed positively by both participating teachers and administrators as a tool for increasing teacher quality through observing, learning, and collaborating with their peers, educational leaders are encouraged to strengthen the program design by removing the frustrations related to teacher substitutes and, thereby, lessening the stresses teachers experience and reluctance they have in leaving their classrooms to conduct peer observation. Districts need to provide assurances to teachers that there is administrative support and a funding commitment for the program to achieve maximum success

Impact of Adoption of Improved Groundnut Varieties on Factor Demand and Productivity in Uganda

The study analyzed the impact of adoption of improved groundnut varieties on farm inputs demand and productivity using instrumental variables approach. The data was collected from a simple random sample of 161 groundnut farmers in Eastern Uganda. Econometric results show significant increase in expenditure on improved seed and labor among adopters relative to the non-adopters. Adoption of improved varieties significantly increased groundnuts yield, by about 1688kg per hectare. Thus, more effort is needed to increase farmers’ access to improved varieties. The Government and partners should facilitate the development of local seed multiplication systems to reduce the cost of improved seed..Production Economics, Productivity Analysis, Research and Development/Tech Change/Emerging Technologies,

Deconstructing Feminist Positions in Unigwe’s “Possessing The Secret Of Joy” and Aidoo’s “The Girl Who Can”

For many years, African women have been blaming men for the inferior position of the female gender in African societies. In this blame game, the patriarchal and cultural stipulations of societies are not left out since they present the male gender as superior. This observation is emphasised by the myriads of texts on feminism which largely present discourses that highlight the roles of the male gender and patriarchy in perpetuating female otherness. In doing so, the females are portrayed as mere victims who do not play any active roles in this ordeal and are therefore exonerated from blame. This notwithstanding, a close study of events in patriarchal societies and the evolving contemporary current of thought in feminist domains questions the portrayal of women as helpless victims of patriarchy. By using the theories of feminism and deconstruction and by focusing on the themes and language of the stories, this paper seeks to unearth some patterns in Unigwe’s “Possessing the Secret of Joy” and Aidoo’s “The Girl Who Can” which speak to the involvement of women as agents of patriarchy. It also argues that some of the time too, men can be victims or subjugates of patriarchy in the African context. The paper concludes that the fight against patriarchy remains the lot of both genders and not in the blame game

Market Orientation in MSME: A Qualitative Case Study of MSME in Zimbabwe

In different sectors and countries, the importance of market orientation has been widely recognised in improving organisational performance in large organisations. However the concept of market orientation is being misunderstood by the Micro Small and Medium Enterprises particularly from developing countries context. These misunderstandings led to this study which mainly focused on examining the understanding of market orientation, antecedents and consequences of market orientation by Micro Small and Medium Enterprises operating in the wood and metal furniture manufacturing industry of Zimbabwe. The research was more qualitative in nature and used face to face interviews to gather insights into the market orientation practices, antecedents and consequences in Micro Small and Medium Enterprises. The study’s results revealed that Micro Small and Medium Enterprises lack greater understanding of the market orientation concept, its antecedences and consequences. This has been revealed by the majority of MSME’s top management not having full support of market orientation and not being risk takers. MSMEs confessed not having marketing budgets, research and development teams, marketing plans and they do not see its importance to the success of their businesses. These enterprises are operating more informally and concentrate on methods of increasing products purchase, increasing market share and customer retention. Basing on these findings, the paper provides some managerial implications, limitations of the study and recommendations for future researches. Keywords: Market orientation, Qualitative, Micro Small Medium Enterprises, Zimbabw