The conceptually simple process of linking carbohydrate units by glycosylation has proven to be one of the most difficult synthetic processes to control from a stereochemical perspective. In particular it is the stereocontrolled synthesis of 1,2-cis glycosyl linkages (e.g. α-glucosides, β-mannosides) which poses the most difficult challenge. The research presented in this thesis describes new ways in which stereocontrol in glycosylation reactions can be achieved. New methods of neighbouring group participation have been explored, utilising novel protecting groups at the 2-postion of a series of glycosyl donors. In particular the use of glucosyl donors bearing a 2-O-(2-(2,4,6- trimethoxyphenyl)thio)ethyl protecting group at the 2-hydroxyl, have shown exceptional α-selectivity especially when a completely armed donor was used. Work within this thesis also describes the use of chiral Brønsted acid catalysts in stereoselective glycosylation reactions. However the yields and stereoselectivity obtained were not very encouraging.

The rapid accumulation of numerous sequenced genomes has provided a golden opportunity for ancestral state reconstruction studies, especially in the whole genome reconstruction area. However, most ancestral genome reconstruction methods developed so far only focus on gene or replicon sequences instead of whole genomes. They rely largely on either detailed modeling of evolutionary events or edit distance computation, both of which can be computationally prohibitive for large data sets. Hence, most of these methods can only be applied to a small number of features and species. In this dissertation, we describe the design, implementation, and evaluation of an ancestral genome reconstruction system (REGEN) for bacteria. It is the first bacterial genome reconstruction tool that focuses on ancestral state reconstruction at the genome scale instead of the gene scale. It not only reconstructs ancestral gene content and contiguous gene runs using either a maximum parsimony or a maximum likelihood criterion but also replicon structures of each ancestor. Based on the reconstructed genomes, it can infer all major events at both the gene scale, such as insertion, deletion, and translocation, and the replicon scale, such as replicon gain, loss, and merge. REGEN finishes by producing a visual representation of the entire evolutionary history of all genomes in the study. With a model-free reconstruction method at its core, the computational requirement for ancestral genome reconstruction is reduced sufficiently for the tool to be applied to large data sets with dozens of genomes and thousands of features. To achieve as accurate a reconstruction as possible, we also develop a homologous gene family prediction tool for preprocessing. Furthermore, we build our in-house Prokaryote Genome Evolution simulator (PEGsim) for evaluation purposes. The homologous gene family prediction refinement module can refine homologous gene family predictions generated by third party de novo prediction programs by combining phylogeny and local gene synteny. We show that such refinement can be accomplished for up to 80% of homologous gene family predictions with ambiguity (mixed families). The genome evolution simulator, PEGsim, is the first random events based high level bacteria genome evolution simulator with models for all common evolutionary events at the gene, replicon, and genome scales. The concepts of conserved gene runs and horizontal gene transfer (HGT) are also built in. We show the validation of PEGsim itself and the evaluation of the last reconstruction component with simulated data produced by it. REGEN, REconstruction of GENomes, is an ancestral genome reconstruction tool based on the concept of neighboring gene pairs (NGPs). Although it does not cover the reconstruction of actual nucleotide sequences, it is capable of reconstructing gene content, contiguous genes runs, and replicon structure of each ancestor using either a maximum parsimony or a maximum likelihood criterion. Based on the reconstructed genomes, it can infer all major events at both the gene scale, such as insertion, deletion, and translocation, and the replicon scale, such as replicon gain, loss, and merge. REGEN finishes by producing a visual representation of the entire evolutionary history of all genomes in the study. / Ph. D.

Combating the effects of the global recession that hampered the economies of various nations has been endeavoured by many governments since 2008. The South African government’s stand to do this shows that it is possible to return the economy back to its glory days, however, the duration of this process of overturning the same is unknown. The government has raised policies and programs, one of which being the New Growth Path (NGP) to combat these effect. This programme, inter alia, calls for increased government expenditure to facilitate job creation through infrastructure development. It is trite economic principles that government expenditure has to be balanced with its revenue collection, otherwise it might lead to budget deficit. Prolonged budget deficit, naturally, is not ideal for a nation’s economy as the same increases government borrowing, results in higher taxes, and affects inflation. While government revenue is mostly financed through taxes, studies show that increasing taxes is also to the detriment for the economy. Therefore, there is a need for disenable policy stand to be taken in respect of the government’s programme, as well as the generation of revenue to support the same. In this regard, one of the ways being advanced by this research in respect of a better combating the recession is to utilise economic legislations enacted in the country. Amongst other economic legislations in South Africa this paper discusses Income Tax Act (SA ITA) (which regulate the persons to pay income taxes) and Competition Act (which regulate fair competition). The focus of this dissertation revolves around the impact competition law remedies have on the income taxation process. The aim of the research is to analyse the possible loopholes in the current legislation that might hamper a government revenue generation to support its new growth path. This was met through an extensive study of relevant literature in competition and income tax laws in South Africa and also comparative analysis with relevant laws of the United States of America (USA). The main conclusion drawn from this research is that there is an impact of the current competition law remedies on the income taxation process. This research promotes and argues for a change in approach, through government enactment of clear and certain laws both in the field of competition law and tax law. This change would assist government in raising revenue more effectively and achieve it economic growth path and, in turn, combat the global economic crisis that affected the economy. / Dissertation (LLM)--University of Pretoria, 2012. / Mercantile Law / unrestricted

Submitted by LUIZ PEREIRA (lp0709@gmail.com) on 2018-07-13T17:12:38Z No. of bitstreams: 1 Tese Final - LUIZ PEREIRA NUNES JUNIOR.pdf: 6221499 bytes, checksum: c48e4ec68c518b7d7e45ae47732e5abc (MD5) / Approved for entry into archive by ÁUREA CORRÊA DA FONSECA CORRÊA DA FONSECA (aurea.fonseca@fgv.br) on 2018-07-16T12:32:30Z (GMT) No. of bitstreams: 1 Tese Final - LUIZ PEREIRA NUNES JUNIOR.pdf: 6221499 bytes, checksum: c48e4ec68c518b7d7e45ae47732e5abc (MD5) / Made available in DSpace on 2018-07-24T18:03:07Z (GMT). No. of bitstreams: 1 Tese Final - LUIZ PEREIRA NUNES JUNIOR.pdf: 6221499 bytes, checksum: c48e4ec68c518b7d7e45ae47732e5abc (MD5) Previous issue date: 2018-06-18 / Objetivo - Este estudo pretende avaliar os impactos da implantação de um modelo orientado por resultado numa cultura burocrática. Metodologia - A pesquisa utilizou o estudo de natureza qualitativa, pelo fato de este proporcionar a investigação que melhor permite explorar, descobrir e entender a realidade de um fenômeno, observando o “valor” das evidências que podem ser obtidas, o que proporciona ao pesquisador detalhes relevantes dificilmente alcançados com o enfoque quantitativo. Para obter a maior percepção do fenômeno em estudo, utilizou-se como método de investigação o estudo de caso quanto aos meios, exploratório quanto aos fins, do tipo 1. O plano de pesquisa adotou uma extensa pesquisa bibliográfica, com o intuito de melhor se familiarizar com a investigação em questão. Durante essa fase foi também definida a questão de investigação e formuladas as questões norteadoras a serem investigadas com entrevistas semiestruturadas. Resultados – O estudo de caso mostrou que, apesar de existirem limitantes para a transição entre o modelo de administração burocrática e o modelo de administração gerencial, esta é possível, como demonstrado na Prefeitura do Rio de Janeiro (SMUIH). Ficou caracterizada também a universalidade do modelo de administração gerencial, que pode ser aplicado a qualquer organização pública, municipal, estadual ou federal. Limitações – A principal limitação da pesquisa está na mudança na Prefeitura entre os anos 2016 e 2017, com troca de prefeito, secretários e diretrizes. Algumas informações da gestão anterior podem não estar disponíveis, não serem de conhecimento do novo time ou, ainda, a coleta e o registro de dados podem ter sofrido descontinuidade. Contribuições práticas – A partir desses resultados, as entidades públicas podem, além de enriquecer as discussões sobre a burocracia, aperfeiçoar sua gestão, buscando atingir melhores resultados e qualidade na entrega de seus produtos e serviços ao cidadão. Contribuições sociais – Devido ao elevado impacto do tema na sociedade, os dois modelos devem ser questionados para melhores resultados. O interesse crescente no modelo de administração gerencial deve-se à importância e à urgência em resolver os problemas públicos que enfrenta o mundo. Além disso, o pragmático reconhecimento de que os governos sozinhos não podem resolver efetivamente muitos desses problemas é algo diferente para os novos tempos. Originalidade – Este estudo contribui com informações relevantes para a melhoria do modelo burocrático, que podem ser aplicadas em muitos contextos diferentes e a qualquer entidade. O modelo burocrático tradicional vem se distanciando do cidadão, entretanto, atender às transformações é uma necessidade das organizações públicas, mesmo que não haja uma chamada “receita de bolo”, o que leva à convergência a um novo modelo gerencial. / Purpose - This study aims to evaluate the impacts of the implantation of a result- oriented model in a bureaucratic culture. Design/Methodology - The research used a qualitative study, since it provides a better investigation to explore, discover and understand the reality of a phenomenon, observing the "value" of the evidences that can be obtained. It provides relevant details to the researcher, which are difficult to capture with a quantitative approach. In order to obtain a better perception of the phenomenon under study, the research method employed was a case study, exploratory, type 1. An extensive literature review endorses the research plan and is the base for defining the research question and the guiding questions for the semi-structured interviews. Findings – The results showed that, although there are limitations to the transition between the bureaucratic management model and the managerial administration model, the transition is possible as demonstrated by the City of Rio de Janeiro (SMUIH). It also highlighted the universality of the managerial administration model, as it is possible to apply it to any public, Municipal, State or Federal organization. Research limitations – The main research limitation is the change in the City Hall government between 2016 and 2017 with the changing of Mayor, Secretaries and guidelines. Due to this government change, some information from the previous management may not be available, not be known by the new team, or the collection and recording of data may have suffered discontinuity. Practical implications– From these results, public entities can not only enrich discussions about bureaucracy, they can also improve their management in order to achieve better results and quality in the delivery of their products and services to citizens. Social implications– Due to the high impact on society, one should question both models for achieving best results. The growing interest for the managerial administration model is due to the importance and urgency of solving the public problems facing the world. Besides, the pragmatic recognition that governments alone cannot effectively solve many of these problems is something different for these new times. Originality– This study contributes with relevant information to the improvement of the bureaucratic model, which applies in many different contexts and to any entity. The traditional bureaucratic model has been distancing itself from the citizen, although responding to transformations is a necessity of public organizations, even if there is no "cake recipe" which leads to the convergence to a new managerial model.

Monocytes exhibiting a pro-inflammatory phenotype play a key role in adhesion and development of atherosclerotic plaques. As an alternative to smoking, next-generation tobacco and nicotine products (NGP) are now widely used. However, little is known about their pro-inflammatory effects on monocytes. We investigated cell viability, anti-oxidant and pro-inflammatory gene and protein expression in THP-1 monocytes after exposure to aqueous smoke extracts (AqE) of a heated tobacco product (HTP), an electronic cigarette (e-cig), a conventional cigarette (3R4F) and pure nicotine (nic). Treatment with 3R4F reduced cell viability in a dose-dependent manner, whereas exposure to alternative smoking products showed no difference to control. At the highest non-lethal dose of 3R4F (20%), the following notable mRNA expression changes were observed for 3R4F, HTP, and e-cig respectively, relative to control; HMOX1 (6-fold, < 2-fold, < 2-fold), NQO1 (3.5-fold, < 2-fold, < 2-fold), CCL2 (4-fold, 3.5-fold, 2.5-fold), IL1B (4-fold, 3-fold, < 2-fold), IL8 (5-fold, 2-fold, 2-fold), TNF (2-fold, 2-fold, < 2-fold) and ICAM1 was below the 2-fold threshold for all products. With respect to protein expression, IL1B (3-fold, < 2-fold, < 2-fold) and IL8 (3.5-fold, 2-fold, 2-fold) were elevated over the 2-fold threshold, whereas CCL2, TNF, and ICAM1 were below 2-fold expression for all products. At higher doses, greater inductions were observed with all extracts; however, NGP responses were typically lower than 3R4F. In conclusion, anti-oxidative and pro-inflammatory processes were activated by all products. NGPs overall showed lower responses relative to controls than THP-1 cells exposed to 3R4F AqE.