L’ataxie de Friedreich (AF) est une maladie neurodégénérative à transmission autosomique récessive. Cette pathologie se caractérise par une dégénérescence spinocérébelleuse, une cardiomyopathie hypertrophique qui est la cause majeure du décès des patients, et un risque accru de diabète. La mutation majoritaire causant l’AF est une hyper-expansion de triplet GAA dans le premier intron du gène FXN codant la frataxine, une protéine mitochondriale ubiquitaire codée par le génome nucléaire. Ces hyper-expansions instables conduisent à une inhibition de la transcription du gène FXN et donc à une baisse d’expression de la frataxine. Aucun traitement curatif n’est disponible à l’heure actuelle pour cette maladie. Seule une meilleure compréhension de la physiopathologie de l’AF permettra d’envisager le développement de stratégies thérapeutiques efficaces. Plusieurs travaux montrent que la frataxine intervient dans la biosynthèse des centres Fe-S, mais son rôle exact dans cette voie, et sa possible contribution dans d’autres processus biochimiques, doivent encore être élucidés. Par une approche de protéomique quantitative utilisée pour la première fois sur des lignées lymphocytaires issues d’un patient AF et d’un individu non atteint, nous avons pu établir le profil d’expression des protéines associées à un déficit en frataxine. Ces nouvelles données confirment les processus altérés décrits pour l’AF, et ont permis la mise en exergue de nouveaux mécanismes mitochondriaux impactés, comme l’altération de la voie d’importation via CHCHD4. La mitochondrie interagissant avec le réticulum endoplasmique (RE), nous avons analysé et comparé l’impact d’un stress induit par la thapsigargine ciblant le RE sur le profil d’expression des protéines des lymphocytes B AF et contrôles. Ces analyses montrent que le déficit en frataxine rend les mitochondries des cellules de patients AF plus sensibles à un stress du RE, nécessitant la mise en place de réponses adaptatives spécifiques. L’approfondissement des mécanismes altérés associés au déficit en frataxine, avec et sans stress exogène, permettront d’une part, de mieux comprendre la pathogenèse de l’AF et d’autre part, de proposer des stratégies thérapeutiques adaptées. / Friedreich’s ataxia (FRDA) represents the most frequent type of autosomal-recessively inherited ataxia associated with a cardiomyopathy, which is the main cause of the death, and a risk of diabetes. FRDA is caused by mutations in the FXN gene, encoding mitochondrial frataxin, arising from an unstable hyperexpansion of GAA triplet repeats in the first intron of the gene. This hyperexpansion leads to FXN gene silencing and a quantitative decreased expression of frataxin. However despite many efforts to overcome any of these abnormalities, there is currently no efficient treatment to cure or even stop the progression of this disease, mostly because many aspects of the pathological consequences of frataxin depletion are still not fully understood. The precise role of frataxin is still under debate. A key function of frataxin in Fe-S cluster biogenesis has now been clearly pointed out, but how its role in this essential cellular pathway correlates with the pathophysiology of FRDA needs to be further investigated. To better understand the biochemical sequelae of frataxin reduction, global protein expression analysis was performed using quantitative proteomic experiments in Friedreich’s ataxia patient-derived B-lymphocytes as compared to controls. We were able to confirm a subset of changes in these cells and importantly, we observed previously unreported signatures of protein expression. Mitochondria are closed to endoplasmic reticulum (ER) and we used quantitative proteomic experiments to screen and analyze the impact of ER stress induced with thapsigargin in Friedreich’s ataxia patient-derived B-lymphocytes as compared to controls. We observed that the frataxin deficiency makes cells more sensitive to ER stress and leads to an up-regulation of specific adaptive mechanisms. The identification of a core set of proteins changing in the FRDA pathogenesis, with or without exogenous stress, is a useful tool in trying to decipher the function(s) of frataxin in order to clarify the metabolic disease process and find future targets for novel therapeutic strategies.

The purpose of the study was to determine how South African mathematics teachers were integrating computers into their classrooms. The study was a response to the low achievement scores in mathematics as attained by grade nine learners in the 2011 Trends in International Mathematics and Science Study (TIMSS). TIMSS 2011 assessed Grade four and eight learners. However, South Africa as well as Botswana and Honduras opted to administer the Grade eight assessment to their Grade nine learners instead. South Africa’s Grade nine learners achieved an average score of 352 (35.2%) out of a possible 1 000 points. This quantitative secondary data analysis study utilised data collected from mathematics teachers from 298 schools in South Africa. The dataset was analysed using descriptive analysis that included percentages as well as the Pearson two-way Chi-square tabulations. The major finding of the study is that 73. 9% of South African mathematics teachers are still not integrating computers into mathematics education. Results showed that teachers are mostly using computers for preparation (35.5%) and administration (65.3%) purposes. Even though 45.5% of the teachers reported that they feel comfortable using computers, others feel that they are still in need of technical support. Moreover, the findings showed that 64.8% of the teachers do not attend professional development programmes that focus on the integration of Information Technology (IT) into mathematics. / Dissertation (MEd)--University of Pretoria, 2017. / Science, Mathematics and Technology Education / MEd / Unrestricted

La presente investigación está enfocada en la industria de explosivos, la cual trabaja directamente con distintos sectores en el país, tales como el sector de construcción, el sector de defensa y la industria minera, siendo esta última la que durante los últimos 60 años ve a los explosivos como recurso necesario y primordial, para ejercer su determinado fin. Por esto, el foco de la presente tesis es analizar cuáles son los principales factores que influyeron a las exportaciones de explosivos fabricados a partir del nitrato de amonio (emulsiones), las cuales poseen la partida arancelaria (3602002000), durante los años 2006 al 2017 hacia nuestro país vecino del sur Chile. Para esto la investigación tomo como base diversos estudios tales como Dynamite Market Global Forecast, Global Ammonium Nitrate Explosive Market Size and Industry Trends los cuales detallan sobre un conjunto de factores que impulsan el crecimiento del mercado de explosivos en el mundo. Asimismo, este estudio se basa en un enfoque cualitativo para la determinación de los principales factores y un enfoque cuantitativo para el análisis de la información recabada. En una primera etapa cualitativa, se logró contrastar e identificar una serie de factores claves que influenciaron directamente a las exportaciones de emulsiones peruanas, las cuales se obtuvieron a partir de entrevistas a profundidad realizadas a especialistas dedicados a este rubro. Posterior a la identificación de los factores se compararon los datos obtenidos en una segunda parte de la investigación, la cual se basa en un análisis cuantitativo sobre la información obtenida. . / The present investigation is focused on the explosives industry, which works directly with different sectors in the country, such as the construction sector, the defense sector and the mining industry, the latter being the one that during the last 60 years sees explosives as a necessary and primary resource, to exercise their specific purpose. Therefore, the focus of this thesis is to analyze what are the main factors that influenced the exports of explosives manufactured from ammonium nitrate (emulsions), which have the tariff heading (3602002000), during the years 2006 to 2017 To our neighboring country in southern Chile. For this, the research was based on various studies such as Dynamite Market Global Forecast, Global Ammonium Nitrate Explosive Market Size and Industry Trends which detail a set of factors that drive the growth of the explosives market in the world. Likewise, this study is based on a qualitative approach for the determination of the main factors and a quantitative approach for the analysis of the information collected. In a qualitative first stage, it was possible to contrast and identify a series of key factors that directly influenced the exports of Peruvian emulsions, which were obtained from in-depth interviews with specialists dedicated to this area. After the identification of the factors, the data obtained in a second part of the investigation were compared, which is based on a quantitative analysis of the information obtained. / Tesis

IT service management is becoming more and more important in the current business environment. Especially the IT Infrastructure Library (ITIL) is a widely adopted and accepted IT service management framework (Wagner 2006). Organizations that adopt one of the IT service management frameworks expect to achieve a large range of benefits through the use of the frameworks. The major benefits that are expected to be realised include reduced costs, IT services that are tailored to the business needs, a higher quality of IT services, and improved customer satisfaction (OGC 2007a). Despite the growing importance and acceptance of IT service management and ITIL, there is not much literature that is concerned with the benefits that can be realised when one of the relevant IT service management frameworks is in place. Only a few studies were published in conference proceedings (e.g. Hochstein et al. 2005, Potgieter et al. 2005, Cater-Steel et al. 2006). Even though these studies were able to confirm some of the claims made by the Office of Government Commerce (OGC), the publisher of the ITIL series, there are still a lot of claims that are not evaluated to date. This thesis is taking a Monte-Carlo method based simulation approach to identify some of the benefits of the ITIL for customer service. To achieve this, an initial research model was developed that represents the four most likely benefits for customer service of the use of ITIL and their relationship with customer service and the generation of business value. Subsequently the different path ways for the relationships were explored and models for each of the possible paths were designed. These models include a mediated model, an unmediated model and a partially mediated model. After defining the estimates and constraints for the simulation, the simulation was executed using a MS Excel spreadsheet. The simulation results presented a large amount of data for each of the models and their relationships. The models produced normal distributions and showed stability for changed input and throughput parameters. The analysis of the findings showed that the changes in estimates for each of the models and the associated results of the simulation followed a linear pattern. The linearity of the models combined with the normal distribution of the results offers a lot of opportunities for the use of the developed models. A further enhancement through a test with real-life data could provide the basis for a tool to quantitatively predict the impact of an ITIL implementation on customer service and the creation of value for the business. In addition the four most likely contributors to improved customer service based on the use of ITIL have been identified from a literature review. The identified contribution towards improved customer service of these four beneficiary factors is supported by the results of the simulation. Therefore the results of this thesis provide the research community with a model that could provide the basis for further exploration of the beneficiary effects of ITIL on customer service.

IT service management is becoming more and more important in the current business environment. Especially the IT Infrastructure Library (ITIL) is a widely adopted and accepted IT service management framework (Wagner 2006). Organizations that adopt one of the IT service management frameworks expect to achieve a large range of benefits through the use of the frameworks. The major benefits that are expected to be realised include reduced costs, IT services that are tailored to the business needs, a higher quality of IT services, and improved customer satisfaction (OGC 2007a). Despite the growing importance and acceptance of IT service management and ITIL, there is not much literature that is concerned with the benefits that can be realised when one of the relevant IT service management frameworks is in place. Only a few studies were published in conference proceedings (e.g. Hochstein et al. 2005, Potgieter et al. 2005, Cater-Steel et al. 2006). Even though these studies were able to confirm some of the claims made by the Office of Government Commerce (OGC), the publisher of the ITIL series, there are still a lot of claims that are not evaluated to date. This thesis is taking a Monte-Carlo method based simulation approach to identify some of the benefits of the ITIL for customer service. To achieve this, an initial research model was developed that represents the four most likely benefits for customer service of the use of ITIL and their relationship with customer service and the generation of business value. Subsequently the different path ways for the relationships were explored and models for each of the possible paths were designed. These models include a mediated model, an unmediated model and a partially mediated model. After defining the estimates and constraints for the simulation, the simulation was executed using a MS Excel spreadsheet. The simulation results presented a large amount of data for each of the models and their relationships. The models produced normal distributions and showed stability for changed input and throughput parameters. The analysis of the findings showed that the changes in estimates for each of the models and the associated results of the simulation followed a linear pattern. The linearity of the models combined with the normal distribution of the results offers a lot of opportunities for the use of the developed models. A further enhancement through a test with real-life data could provide the basis for a tool to quantitatively predict the impact of an ITIL implementation on customer service and the creation of value for the business. In addition the four most likely contributors to improved customer service based on the use of ITIL have been identified from a literature review. The identified contribution towards improved customer service of these four beneficiary factors is supported by the results of the simulation. Therefore the results of this thesis provide the research community with a model that could provide the basis for further exploration of the beneficiary effects of ITIL on customer service.

Over the last few decades, microfinance industry has played an essential role in alleviating poverty level and helping the underprivileged, by enabling access to myriads of financial services. Statistics from the World Bank reveals that, currently, only 4% of the underprivileged were served out of the 3 billion potential clients. Such results were due to several claims, particularly the operational and financial challenges faced by the MFIs in the constant flux, inviting more attentions towards its performance. While explicit focuses were given by many researchers towards mobile banking and Information Communication Technology (ICT) and online services in improving the MFIs performance, the study on how Social Media, as a rapidly growing online phenomenon, could affect the MFIs performance remain scarce. Hence, this study was aimed at investigating and clarifying the impact of social media on MFIs, based on four dimensional performance indicators: efficiency, financial sustainability, portfolio quality, and outreach. A model was developed utilising Resource Based-View (RBV) Theory, to test the relationship between social media application and organisational performance. A quantitative approach has been adopted employing from web-based questionnaires, to collect data from MFIs employees in developing countries such as Kenya, India and Jordan. Structured Equation Modelling (SEM) technique (i.e. SPSS and AMOS 20 software) was used as a tool to analyse the responses. Results revealed a significant influence of the social media over the MFIs performance, offering valuable insights to both researchers and practitioners in the domain of micro-finance, as well as social media – conforming that the adoption of social media as marketing, advertising and communication tools could significantly improve the MFIs performance. Keywords: Microfinance, Microfinance Institution Performance, Social Media, Resource Based View Theory.

Teachers need to develop 21st Century skills and be competent users of ICT to integrate it successfully in their everyday instruction and learning activities. The goal of this Secondary Data Analysis (SDA) study is to determine the proportion of South African Science and Mathematics teachers who experience a lack of ICT-related skills and pedagogical skills related to the integration of ICT in instruction and learning as an obstacle. Furthermore it has been investigated whether these teachers are willing to be trained. This study is a response to the distressing outcome of the The Second International Technology in Education Study (SITES 2006), an international survey that was conducted by the International Association for the Evaluation of Educational Achievement (IEA), indicating that South Africa has the lowest ICT integration among the SITES 2006 participating countries (16% for Science and 18% for Mathematics). The current study followed a basic SDA of the SITES 2006 dataset relating to South African Science and Mathematics teachers and adopted an integrated qualitative-quantitative approach. The results indicate that there is a great need for South African Science and Mathematics teachers to attend professional development activities since there are many teachers who lack ICT-related skills (55%) and pedagogical skills related to the integration of ICT in instruction and learning (62%). The teachers who experience a lack of ICT-related skills and pedagogical skills are willing to be trained (88% and 93% respectively). These results imply that the challenge now rests with the government of South Africa to make sure that professional development activities that are both relevant and subject-specific are offered on a regular basis. The Government needs to devise strategies to promote professional development for the improvement of ICT integration into South African classrooms. / Dissertation (MEd)--University of Pretoria, 2014. / lk2014 / Science, Mathematics and Technology Education / MEd / Unrestricted

En la actualidad, la páprika peruana se encuentra entre los principales proveedores mundiales desde la última década debido a su calidad y su experiencia en agroexportación. Las exportaciones de páprika peruana tienen como principales destinos a España, México y Estados Unidos, siendo este último el de mayor demanda. A pesar de estar entre los principales exportadores mundiales, la páprika peruana no logra consolidarse o mejorar sus niveles de ventas. Entre los años 2012 - 2017, las exportaciones han presentado irregularidades por parte de las exportadoras que en ciertos casos dejaron de enviar al exterior por espacios de un año. En este periodo de seis años, se observa la consolidación de China como proveedor mundial, las consecuencias de la crisis española en la demanda y la importancia del Norte de Lima como productor nacional de páprika. El presente documento analiza los factores determinantes internos y externos que influyen en las exportaciones de páprika del Norte de Lima. Entre los internos se obtienen el desarrollo tecnológico, la edad y tamaño de la empresa. Por parte de los externos, se presenta el acceso al financiamiento. Para este fin, se analizaron las correlaciones existentes entre las variables y el análisis factorial. La investigación es cuantitativa, no experimental, transeccional y correlacional. Los resultados muestran que los factores analizados son significativos para la actividad exportadora de la páprika debido a que se encuentran muy correlacionadas. / At present, Peruvian paprika is among the world's leading suppliers in the last decade due to its quality and experience in the agro-export sector. The exports of Peruvian paprika have as main destinations to Spain, Mexico and the United States, the latter is the one with the highest demand. Despite being among the world's leading exporters, Peruvian paprika does not manage to consolidate or improve its sales levels. In the years 2012 to 2017, the exports have presented irregularities on the part of the exporters that in certain cases stopped sending abroad for spaces of one year. In this period of six years, we see the consolidation of China as a global supplier, the consequences of the Spanish crisis on demand and the importance of Northern Lima as a national producer. This document analyzes the internal and external determinants that influence the exports of paprika from the North Region of Lima. Among the interns, the technological development, the age and size of the company are obtained. On the part of outsiders, access to financing is presented. The existing correlations between the variables and the factorial analysis were analyzed. The research is quantitative, not experimental, transectional and correlational. The results show that the factors analyzed are significant for the export activity of paprika because they are correlated. / Tesis

Abstract A profile on alcohol consumption among South African dentists – A dentist’s perspective: JH Olivier Background This study investigated alcohol use linked to the stress of a selected sample of South African dentists. The only other related topic in South Africa, that the researcher could find, was done in 1996 at the University of Stellenbosch. The literature suggests that prevalence studies of substance use and abuse rarely include dentists. Methods A dominant quantitative approach with a less dominant qualitative approach was utilized. The quantitative-descriptive design (survey with a questionnaire) was used to obtain data with regard to biographical/background information, stress and coping, quantity and frequency of alcohol use, and dysfunction as a result of alcohol use among a randomly selected sample of 110 South African dentists with a response rate of 70%. The respondents’ perspective on alcohol use linked to the stress of the dental profession with recommendations were also obtained. For the qualitative data collection, the researcher utilized the collective case study. He planned semi-structured interviews with an interview schedule with five dentists that have already had treatment for alcohol abuse or were self-characterized as problem drinkers. Unfortunately, two of the respondents who characterized themselves as heavy alcohol users died before they could be interviewed. Because of ethical reasons and the sensitivity of the topic they could not be replaced. Findings The quantitative study indicated that: (1) the respondents experienced significant amounts of occupational stress (2) the majority of the respondents do physical exercise to reduce their stress (3) a great number of respondents socialize with friends to reduce their stress (4) some respondents actually use alcohol to reduce their stress (5) stress levels of the respondents in private practice and stress levels of the respondents in other sectors are the same (6) alcohol consumption of male and female dentists is the same (7) respondents who reported less areas of stress consumed more alcohol than those who reported more areas of stress (8) a great number of the respondents experience high stress levels but do not use alcohol, or they only use alcohol to socialize (9) less than 3% of the respondents reported that alcohol use has affected their work as a dentist (10) the majority of the respondents believe that some dentists consume alcohol as a coping mechanism concerning social anxiety, occupational stress and personal factors. The qualitative study indicated that: (1) the habit of alcohol use that may lead to alcohol dependency starts at university (2) the respondents, who had treatment for alcohol dependency, experienced high levels of occupational stress (3) the respondents link their dependency directly to the stress and strain of their profession. Conclusions There are more intense and less intense stressors among South African dentists and there are some dentists that consume alcohol to relieve the stress and strain of their profession. However, the majority only use alcohol as a way of socializing. Less than 3% of the respondents reported that alcohol use has affected their work as a dentist. Recommendations Modules on coping mechanisms linked to the stress and strain of the dental profession should be included in the curricula at dental schools. The compulsory CPD programme of the HPCSA should include stress management and healthy coping mechanism courses. / Thesis (PhD)--University of Pretoria, 2009. / Social Work and Criminology / unrestricted

Ce travail entreprend d'évaluer l'évolution de l'acquisition phonologique par des étudiants français des contrastes anglais /ɪ/-/i:/ et /ʊ/-/u:/. Le corpus étudié provient d'enregistrements de conversations spontanées menées avec des étudiants natifs. 12 étudiants, 9 femmes et 3 hommes,ont été suivis lors de 4 sessions espacées chacune d'un intervalle de six mois. L'approche adoptée est résolument quantitative, et agnostique quant aux théories d'acquisition d'une deuxième langue (par exemple Flege 2005, Best 1995,Kuhl 2008). Afin d'estimer les éventuels changements de prononciation, une procédure automatique d'alignement et d'extraction des données acoustiques a été conçue à partir du logiciel PRAAT (Boersma 2001). Dans un premier temps, deux autres logiciels (SPPAS et P2FA, Bigi 2012 et Yuan &Liberman 2008) avaient aligné les transcriptions des enregistrements au phonème près. Plus de 90 000 voyelles ont ainsi été analysées. Les données extraites sont constituées d'informations telles que le nombre de syllabes du mot, de sa transcription acoustique dans le dictionnaire, de la structure syllabique, des phonèmes suivant et précédant la voyelle, de leur lieu et manière d'articulation, de leur appartenance ou non au même mot, mais surtout des relevés formantiques de F0, F1, F2, F3 et F4. Ces relevés formantiques ont été effectués à chaque pourcentage de la durée de la voyelle afin de pouvoir tenir compte des influences des environnements consonantiques sur ces formants. Par ailleurs, des théories telles que le changement spectral inhérent aux voyelles (Nearey & Assmann(1986), Morrison & Nearey (2006), Hillenbrand (2012),Morrison (2012)), ou des méthodes de modélisation du signal telles que la transformation cosinoïdale discrète(Harrington 2010) requièrent que soient relevées les valeurs formantiques des voyelles tout au long de leur durée. Sont successivement étudiées la fiabilité de l'extraction automatique, les distributions statistiques des valeurs formantiques de chaque voyelle et les méthodes de normalisation appropriées aux conversations spontanées. Les différences entre les locuteurs sont ensuite évaluées en analysant tour à tour et après normalisation les changements spectraux, les valeurs formantiques à la moitié de la durée de la voyelle et les transformations cosinoïdales. Les méthodes déployées sont les k plus proches voisins, les analyses discriminantes quadratiques et linéaires, ainsi que les régressions linéaires à effets mixtes. Une conclusion temporaire de ce travail est que l'acquisition du contraste/ɪ/-/i:/ semble plus robuste que celle de /ʊ/-/u:/. / This study undertakes to assess the evolution of the phonological acquisition of the English /ɪ/-/i:/ and /ʊ/-/u:/ contrasts by French students. The corpus is made up of recordings of spontaneous conversations with native speakers. 12 students, 9 females and 3 males, were recorded over 4 sessions in six-month intervals. The approach adopted here is resolutely quantitative, and agnostic with respect to theories of second language acquisition such as Flege's, Best's or Kuhl's. In order to assess the potential changes in pronunciations, an automatic procedure of alignment and extraction has been devised, based on PRAAT (Boersma 2001). Phonemic and word alignments had been carried out with SPPAS (Bigi 2012) and P2FA (Yuan & Liberman 2008) beforehand. More than 90,000 vowels were thus collected and analysed. The extracted data consist of information such as the number of syllables in the word, the transcription of its dictionary pronunciation, the structure of the syllable the vowel appears in, of the preceding and succeeding phonemes, their places and manners of articulation, whether they belong to the same word or not, but also especially of the F0, F1, F2, F3 and F4 formant values. These values were collected at each centile of the duration of the vowel, in order to be able to take into account of the influences of consonantal environments. Besides, theories such as vowel-inherent spectral changes (Nearey & Assmann (1986), Morrison & Nearey (2006), Hillenbrand (2012), Morrison (2012)), and methods of signal modelling such as discrete cosine transforms (Harrington 2010) need formant values all throughout the duration of the vowel. Then the reliability of the automatic procedure, the per-vowel statistical distributions of the formant values, and the normalization methods appropriate to spontaneous speech are studied in turn. Speaker differences are assessed by analysing spectral changes, mid-temporal formant values and discrete cosine transforms with normalized values. The methods resorted to are the k nearest neighbours, linear and quadratic discriminant analyses and linear mixed effects regressions. A temporary conclusion is that the acquisition of the /ɪ/-/i:/ contrast seems more robust than that of the /ʊ/-/u:/ contrast.