Thesis (MBA)--Stellenbosch University, 2000. / ENGLISH ABSTRACT: With each passing year and the intensification of competition, strategic management becomes more important. In an ever-changing business environment, management, and especially strategic management, becomes increasingly crucial. This empirical study attempts to conduct a literature study of strategic management in order to develop a strategic planning model. A simplified model is proposed as a framework on which a practical application can be made. Boland PKS, a division of the Board of Executors, has been elected as the organisation to whose strategic management the model will be applied. Boland PKS will be applied to the model in an effort to accept or reject the following statement of the problem: The author is of the opinion that strategic planning is not being applied in Boland PKS. / AFRIKAANSE OPSOMMING: Jaarliks toenemende kompetisie maak strategiese bestuur toenemend belangrik in hedendaagse besigheid. In 'n snel-veranderende wêreld word bestuur, en veral strategiese bestuur, kardinaal. Hierdie empiriese studie poog om 'n literatuur studie in strategiese bestuur te doen ten einde 'n strategiese beplanningsmodel te ontwikkel. 'n Eenvoudige model word dan voorgestel as 'n verwysingsraamwerk vir die praktiese toepassing van die model. Boland PKS, 'n afdeling van die "Board of Executors", is gekies as die organisasie waarop die model toegepas sal word. Die model sal op Boland PKS toegepas word in a poging om die volgende probleemstelling te aanvaar of te verwerp: " Die skrywer is van mening dat Boland PKS nie strategiese beplanning toepas nie."

This thesis describes the analysis of Very High Energy (VHE) emission from the Active Galactic Nucleus PKS 0537-441. It also aims to put the results in a wider context by implementing previous work done on this source. The data chosen for the analysis is provided by the Fermi-LAT satellite and covers the energy range between 300 MeV and 300 GeV. Initially a lightcurve of the received flux from the source was generated, containing data from August 2008 to April 2017, with a mean flux of 4∗10−8 photons per second per squared centimeter. The lightcurve contained sections of different flux intensities giving periods of special interest, such as a flaring period at August 2008 to August 2011, an enormous flare at April 2010 and a less active period between April 2013 - January 2016 that could be identified for further investigations. The differences in observed flux over time was tested and PKS 0537-441 was found to be a significantly variable source. Spectral Energy Distribution (SED) analysis was performed over both the entire period as well as over the selected subperiods and fitted against models using the tools provided by the Fermi Science Support Center (FSSC). The models used in the fitting was PowerLaw2, LogParabola and PLSuperExpCutoff and the best fit for the data was obtained from the PLSuperExpCutoff, except for the less intense period where the LogParabola gave the best fit. The result from the SED analysis was integrated with results from previous work done on the source, ranging over multiple wavelengths in order to get a SED which spanned over the entire electromagnetic spectrum. Finally, modeling of this multi wavelength SED was performed in order to obtain parameters for the physical processes involved in the creation of the radiation received from PKS 0537-441.

<p>  </p> <p>Biosynthesis of fatty acids and specialized metabolites, such as polyketides, is dependent on the C-C bond forming enzymatic activity of carboxylases and <u>k</u>eto<u>s</u>ynthases (KS). Carboxylases and KS perform complex carbon-carbon bond forming reactions via a ping-pong mechanism; the catalytic interactions of which are still unclear. The KS reaction involves the Claisen condensation of an acylated enzyme with a malonyl-thioester, driven forward by the energy of the malonyl-thioester decarboxylation. Similarly, the carboxylase proceeds via a carboxyl-biotin-enzyme intermediate, and a subsequent C-C bond forming reaction. Engineering the substrate specificity of these enzyme involved in producing polyketides is sought after for the purpose of producing novel, derivative polyketides. These derivative polyketides may have serve as effective new antibiotics, of which discovery has waned. Unfortunately, incomplete understanding of protein-protein interactions, conformational changes, and substrate orientation in catalysis leads to not well informed engineering attempts. A challenge in deducing the catalytic details of enzymes acting on malonyl-thioesters in general is the hyper-reactivity of their β-ketoacid and thioester substrates, which are prone to hydrolysis and decarboxylation. Many structures of malonyl-CoA bound enzymes feature hydrolysis of the thioester, preventing determination of enzyme:substrate interactions in structure-function studies. To work around this problem of innate reactivity, groups have synthesized a variety of acyl-thioester analogs for probing the details of enzyme catalysis with mixed success. The success of these enzyme:analog mechanistic studies appears to hinge upon the similarity of the analog to the natural substrate. Here, we demonstrate the synthesis of near-natural, acyl-thioester analogs, featuring single atom substitutions. Using a novel UV-vis assay, we have determined <em>K</em>i values of our analogs with paradigmatic KSs <em>E. coli</em> FabH. These <em>K</em>i values are marginally higher than the substrate <em>K</em>m values, suggesting the KSs bind the analogs as they would natural substrates. Using this information, we have conducted preliminary X-ray crystallography experiments to determine the carboxylase:analog and KS:analog catalytic interactions, which will allow for new insight into debated C-C bond forming catalytic details. The information presented in this thesis and additional studies on protein-protein interactions can be leveraged into informed engineering studies of PKS enzymes.</p>

<p>Nonribosomal peptides, polyketides, and fatty acids comprise a distinct subset of microbial secondary metabolites produced by similar biosynthetic methods and exhibit broad structural diversity with a high propensity for biological activity. Dedicated studies of these specific microbial small molecules have identified numerous potent actions towards human cells with many clinical translations. Interestingly, most therapeutically used nonribosomal peptides and polyketides were discovered from soil bacteria, meanwhile, bacteria that have co-evolved within a human context, the human microbiota, have barely been explored for secondary metabolites. The central goal of this thesis is to explore the secondary metabolome of human microbiota for nonribosomal peptides and polyketides, which are hypothesized to possess biological activities significant within the human host context. Candidate organisms were chosen for their established connections to human health and evidence suggestive of secondary metabolite production. Specifically, questions about gene to molecule prediction capability, metabolite production, structural diversity, and biological activity were explored from studies of the dental caries linked Streptococcus mutans UA159, from the probiotic Lactobacillus plantarum WCFS1, and the Crohn’s disease associated Faecalibacterium prausnitzii.</p> / Master of Science (MSc)

<p>In the last three decades we have witnessed a remarkable development in the area of integrated circuits. From small logic devices containing some hundred transistors to modern processors containing several tens of million transistors. However, power consumption has become a real problem and may very well be the limiting factor of future development. Designing for low power is therefore increasingly important. To accomplice an efficient low power design, accurate power estimation at early design stage is essential. The aim of this thesis was to set up a power estimation flow to estimate the power consumption at early design stage. The developed flow spans over both RTL- and gate-level incorporating Mentor Graphics Modelsim (RTL-level simulator), Cadence PKS (gate- level synthesizer) and own developed power estimation tools. The power consumption is calculated based on gate-level physical information and RTL- level toggle information. To achieve high estimation accuracy, real node annotations is used together with an own developed on-chip wire model to estimate node voltage swing. </p><p>Since the power estimation may be very time consuming, the flow also includes support for low power design iteration. This gives efficient power estimation speedup when concentrating on smaller sub- parts of the design.</p>

In the last three decades we have witnessed a remarkable development in the area of integrated circuits. From small logic devices containing some hundred transistors to modern processors containing several tens of million transistors. However, power consumption has become a real problem and may very well be the limiting factor of future development. Designing for low power is therefore increasingly important. To accomplice an efficient low power design, accurate power estimation at early design stage is essential. The aim of this thesis was to set up a power estimation flow to estimate the power consumption at early design stage. The developed flow spans over both RTL- and gate-level incorporating Mentor Graphics Modelsim (RTL-level simulator), Cadence PKS (gate- level synthesizer) and own developed power estimation tools. The power consumption is calculated based on gate-level physical information and RTL- level toggle information. To achieve high estimation accuracy, real node annotations is used together with an own developed on-chip wire model to estimate node voltage swing. Since the power estimation may be very time consuming, the flow also includes support for low power design iteration. This gives efficient power estimation speedup when concentrating on smaller sub- parts of the design.

The subject of this thesis is the analysis and modeling of the active galactic nucleus PKS 1510-089. The aim is to present a thorough background of active galactic nuclei combined with the analysis and modeling of a specific active galactic nucleus. The results will then be  linked to previous research and theories about active galactic nuclei. The data used in the analysis were retrieved from the Fermi Gamma-ray Space Telescope. A light curve analysis that extended over 12 years provided knowledge about variability and presented four interesting flaring periods. The four periods underwent a spectral analysis, and the results showed that a log parabolic curvature could best describe all four periods. The last step before the modeling was to create spectral energy distributions for all four periods to retrieve spectral points from wavelengths other than those available from Fermi. Unfortunately, there were only sufficient data for one period. That period was later used in the modeling and resulted in a well-fitted external Compton model, which was compared, with relatively good results, with previous research.

Schwerpunkt dieser Arbeit ist die Emission von hochenergetischer Gammastrahlung aus Aktiven Galaxienkernen, anhand von Beobachtungen mit den MAGIC Teleskopen. Aktive Galaxien entstehen durch die Freisetzung von Gravitationsenergie der Stellarmaterie, die in das zentrale Schwarze Loch fällt. Zwei diametral entgegengesetzte Jets strömen aus dem Kern. Falls einer von diesen Jets zum Beobachter zeigt, wird der aktive Galaxienkern als Blazar bezeichnet. In dieser Doktorarbeit wird die Analyse der MAGIC Beobachtungen von drei Blazaren präsentiert: der bisher unbekannte hochenergetische Blazar 1ES 1727+502 und die bekannten Objekte 3C 279 und PKS 1510-089. Die Quelle 1ES 1727+502 gehört zu der Unterklasse der BL Lac Objekte, die die zahlenmässig größte Klasse an extragalaktischen hochenergetische Objekten ist. Diese Entdeckung beweist, wie wichtig es ist, mehrere und verschiedene Kriterien für die Auswahl von Objekten zu benutzen. Der Blazar 1ES 1727+502 wurde aus einem X-ray Katalog ausgesucht, die Datennahme war unabhängig von dem Aktivitätsstatus der anderen Energiebänder. Die Blazare 3C 279 und PKS 1510-089 gehören zu der Unterklasse des Flat Spectrum Radio Quasars. Es gibt nur drei bekannte Flat Spectrum Radio Quasare. Die Entdeckung von Flat Spectrum Radio Quasaren ist schwierig, weil im leisen Zustand der hochenergetische Fluss niedrig ist. Während eines Flares steigt der Fluss in sehr kurzer Zeit um mehrere Größenordnungen an, deswegen ist die Beobachtung eines Flares schwer zu realisieren aber physikalisch äußerst interessant. Die MAGIC Beobachtungen sind mit Messungen aus anderen Energiebändern kombiniert. Mögliche Interpretationen des beobachteten Verhaltens werden diskutiert. Die Ergebnisse werden erläutert und mit historischen Beobachtungen verglichen. Die offenen Fragen und Probleme, die Ziel zukünftiger Studien sein sollen, werden am Schluss hervorgehoben. / This PhD thesis addresses the problem of understanding the very high energy emission from active galactic nuclei as detected with the MAGIC telescopes. Active galactic nuclei are galaxies powered by the release of gravitational energy of stellar material falling into a black hole, located in their core. Two opposed jets extend from the central region outwards, if one of the them points towards the observer, the source is called a blazar. In this thesis the analysis of MAGIC observations of three different blazars is presented: the newly discovered very high energy blazar 1ES 1727+502, and the two known objects 3C 279 and PKS 1510-089. The source 1ES 1727+502 belongs to the subclass of BL Lac objects, the most numerous class of extragalactic very high energy emitters. This source was selected for observations from an X-ray catalogue and was observed even if no high activity states were reported at lower energies. For this reason, this discovery proves the importance of using several criteria for the selection of very high energy observation targets. The other two objects, 3C 279 and PKS 1510-089, belong to the subclass of flat spectrum radio quasars. We count only three representatives of this class in the very high energy domain. Their detection is critical because during quiescent states they have low flux levels at very high energies. During flaring states, flat spectrum radio quasars exhibit flux enhancements of orders of magnitudes and short time scales. Observations during such states, difficult to catch, are interesting because extreme processes are taking place. Very high energy observations of these three objects are complemented with measurements at lower energies and interpretations of the observed behaviours are discussed. The results are compared with historical observations, highlighting open questions and problems which should be addressed by future studies.

A partir de 280 isolados fúngicos de cana-de-açúcar, 18 cepas foram avaliadas quanto á presença de genes da policetídeo sintase por meio da técnica do PCR. Estes fungos foram identificados taxonomicamente por uma abordagem polifásica, classificando-os dentro de quatro ordens e nove gêneros. A avaliação da atividade biológica demonstrou a presença de metabolitos com propriedades antibióticas quando enfrentados a micro-organismos patogênicos. Segundo a análise de correspondência múltipla, esta atividade poderia estar associada com a local de isolamento dos fungos. Foram detectadas 36 seqüências similares a genes PKS a partir de 17 destes fungos. A análise filogenética do domínio KS, conduzida pelo método de neighbor-joining, indicou que 16 seqüências se acomodaram dentro do grupo monofilético dos PKS envolvidos na produção de policetídeos não reduzidos e as outras 10 seqüências se acomodaram dentro do grupo monofilético dos PKS envolvidos na produção de policetídeos reduzidos. A análise do domínio CMT também apontou que as seqüências podiam se acomodaram em grupos de PKS dependendo do grau de redução do policetídeo, todas as seqüências CMT se relacionaram com PKS envolvidos na produção de policetídeos reduzidos. As análises dos modelos estruturais também demonstraram que as seqüências estavam altamente relacionadas com estruturas protéicas da família das enzimas de condensação, destacando a presença de uma hélice característica que carrega o resíduo de cisteína, responsável pela atividade de condensação. Extratos orgânicos obtidos de cultivos dos fungos foram avaliados parar detectar a presença de compostos tipo lovastatina. Por meio de cromatografia CCDS, detectaram-se bandas de 10 extratos com o mesmo deslocamento que a lovastatina padrão, mas apenas 6 destas foram confirmados por CLAE. O isolado A. flavus CBMAI 1023, foi selecionado para a realização de experimentos de produção a maior escala onde foi possível isolar e caracterizar um novo policetídeo. / From a group of 280 sugarcane-derived fungi 18 strains were assessed for the presence of polyketide synthase genes by PCR approaches. These fungi were identified taxonomically by a polyphasic approach classifying into four orders and nine genres. Biological activity tests showed the presence of antibiotic metabolites against pathogenic microorganisms and the relationship of this activity might be linked with the fungal isolate location by multiple correspondence analyses. 36 sequences similar to PKS genes fragments were detected from 17 of these fungi. A neighbor-joining phylogenetic analysis of the KS domain showed that 16 sequences fit on the monophyletic group of PKS evolved with production of non reduced polyketides, and the other 10 sequences fit on the monophyletic group of PKS evolved with the production of reduced polyketides. CMT domain analysis also pointed that the sequences fit with groups of PKS depending on polyketide reduction grade, all ten related to PKS evolved with the synthesis of reduced polyketides. Protein structural analysis also pointed out that these sequences are closely related with proteins from condensing enzyme family, highlighting the presence of a characteristic helix elbow that bears the cysteine residue responsible for the condensation activity. The fungi were also tested for their capacity of producing lovastatin compounds where chromatographic TLC detected bands from 10 extracts with the same dislocation compared to a lovastatin, but only 6 were confirmed by HPLC. The A. flavus CBMAI (1023) were selected for upscale production experiments, from where it was possible isolate and characterize a new polyketide compound.

A partir de 280 isolados fúngicos de cana-de-açúcar, 18 cepas foram avaliadas quanto á presença de genes da policetídeo sintase por meio da técnica do PCR. Estes fungos foram identificados taxonomicamente por uma abordagem polifásica, classificando-os dentro de quatro ordens e nove gêneros. A avaliação da atividade biológica demonstrou a presença de metabolitos com propriedades antibióticas quando enfrentados a micro-organismos patogênicos. Segundo a análise de correspondência múltipla, esta atividade poderia estar associada com a local de isolamento dos fungos. Foram detectadas 36 seqüências similares a genes PKS a partir de 17 destes fungos. A análise filogenética do domínio KS, conduzida pelo método de neighbor-joining, indicou que 16 seqüências se acomodaram dentro do grupo monofilético dos PKS envolvidos na produção de policetídeos não reduzidos e as outras 10 seqüências se acomodaram dentro do grupo monofilético dos PKS envolvidos na produção de policetídeos reduzidos. A análise do domínio CMT também apontou que as seqüências podiam se acomodaram em grupos de PKS dependendo do grau de redução do policetídeo, todas as seqüências CMT se relacionaram com PKS envolvidos na produção de policetídeos reduzidos. As análises dos modelos estruturais também demonstraram que as seqüências estavam altamente relacionadas com estruturas protéicas da família das enzimas de condensação, destacando a presença de uma hélice característica que carrega o resíduo de cisteína, responsável pela atividade de condensação. Extratos orgânicos obtidos de cultivos dos fungos foram avaliados parar detectar a presença de compostos tipo lovastatina. Por meio de cromatografia CCDS, detectaram-se bandas de 10 extratos com o mesmo deslocamento que a lovastatina padrão, mas apenas 6 destas foram confirmados por CLAE. O isolado A. flavus CBMAI 1023, foi selecionado para a realização de experimentos de produção a maior escala onde foi possível isolar e caracterizar um novo policetídeo. / From a group of 280 sugarcane-derived fungi 18 strains were assessed for the presence of polyketide synthase genes by PCR approaches. These fungi were identified taxonomically by a polyphasic approach classifying into four orders and nine genres. Biological activity tests showed the presence of antibiotic metabolites against pathogenic microorganisms and the relationship of this activity might be linked with the fungal isolate location by multiple correspondence analyses. 36 sequences similar to PKS genes fragments were detected from 17 of these fungi. A neighbor-joining phylogenetic analysis of the KS domain showed that 16 sequences fit on the monophyletic group of PKS evolved with production of non reduced polyketides, and the other 10 sequences fit on the monophyletic group of PKS evolved with the production of reduced polyketides. CMT domain analysis also pointed that the sequences fit with groups of PKS depending on polyketide reduction grade, all ten related to PKS evolved with the synthesis of reduced polyketides. Protein structural analysis also pointed out that these sequences are closely related with proteins from condensing enzyme family, highlighting the presence of a characteristic helix elbow that bears the cysteine residue responsible for the condensation activity. The fungi were also tested for their capacity of producing lovastatin compounds where chromatographic TLC detected bands from 10 extracts with the same dislocation compared to a lovastatin, but only 6 were confirmed by HPLC. The A. flavus CBMAI (1023) were selected for upscale production experiments, from where it was possible isolate and characterize a new polyketide compound.