The aim of this thesis is the analysis, design and implementation of an information system for a wholesale. It focuses on warehouse management and optimization of selected business processes. Hence, processes, which need to be optimized, are identified based on the analysis of the company and its internal functioning. After the data collection and the analysis of the requirements is the information system designed and then implemented in the form of a website application and then it is continuously tested by the automated and the user tests. Later this thesis describes the process of passing down of this system to the client and its impact on the selected company's processes.

In vitro testing includes both cell-based and cell-free systems that can be used to detect toxicity induced by xenobiotics. In vitro methods are especially useful in rapidly gathering intelligence regarding the toxicity of compounds for which none is available such as new chemical entities developed in the pharmaceutical industry. In addition to this, in vitro investigations are invaluable in providing information concerning mechanisms of toxicity of xenobiotics. This type of toxicity testing has gained popularity among the research and development community because of a number of advantages such as scalability to high throughput screening, cost-effectiveness and predictive power. Hepatotoxicity is one of the major causes of drug attrition and the high cost associated with drug development poses a heavy burden on the development of new chemical entities. Early detection of hepatotoxic agents by in vitro methods will improve lead optimisation and decrease the cost of drug development and reduce drug-induced liver injury. Literature highlights the need for a cellbased in vitro model that is capable of assessing multiple toxicity parameters, which assesses a wider scope of toxicity and would be able to detect subtle types of hepatotoxicity. The present study was aimed at developing an in vitro procedure capable of mechanistically profiling the effects of known hepatotoxin dichlorodiphenyl trichloroethane (DDT) and its metabolites, dichlorodiphenyl dichloroethylene (DDE) and dichlorodiphenyl dichloroethane (DDD) on an established liver-derived cell line, HepG2, by evaluating several different aspects of cellular function using a number of simultaneous in vitro assays on a single 96 well microplate. Examined parameters have been suggested by the European Medicines Agency and include: cell viability, phase I metabolism, oxidative stress, mitochondrial toxicity and mode of cell death (apoptosis vs. necrosis). To further assess whether the developed method was capable of detecting hepatoprotection, the effect of the known hepatoprotectant, N-acetylcysteine, was determined. Viability decreased in a dose-dependent manner yielding IC50 values of 54 μM, 64 μM and 44 μM for DDT, DDE and DDD, respectively. Evaluation of phase I metabolism showed that cytochrome P4501A1 activity was dose-dependently induced. Test compounds decreasedlevels of reactive oxygen species, and significantly hyperpolarised the mitochondrialmembrane potential. Assessment of the mode of cell death revealed a significant elevation of caspase-3 activity, with DDD proving to be most potent. DDT alone induced dosedependent loss of membrane integrity. These results suggest that the tested compounds produce apoptotic death likely due to mitochondrial toxicity with subsequent caspase-3 activation and apoptotic cell death. The developed in vitro assay method reduces the time it would take to assess the tested parameters separately, produces results from multiple endpoints that broadens the scope of toxicity compared to single-endpoint methods. In addition to this the method provides results that are truly comparable as all of the assays utilise the same batch of cells and are conducted on the same plate under the exact same conditions, which eliminates a considerable amount of variability that would be unavoidable otherwise. The present study laid a solid foundation for further development of this method by highlighting the unforeseen shortcomings that can be adjusted to improve scalability and predictive power. / Thesis (PhD)--University of Pretoria, 2011. / Pharmacology / unrestricted

<p> Point Pelee National Park in Leamington, Ontario, Canada contained a large component of private farming and recreation until the 1960's. DDT was applied at the park as pest control in the orchards and recreational areas between 1948 and 1960. Recent studies have shown that the compounds DDT, DDE and DDD are highly persistent in the shallow soils of Point Pelee National Park. A laboratory treatability experiment has been effective in the removal of DDT, DDE and DDD from columns packed with soil collected from Point Pelee National Park, using hydroxypropyl-ß-cyclodextrin. Cyclodextrins are microbially produced cyclic oligosaccharides which have a unique hydrophilic shell and a hydrophobic cavity. They are able to form inclusion complexes and aid in the transport of relatively insoluble compounds. A pilotscale field remediation experiment involving the application of hydroxypropyl-ß-cyclodextrin to a Random Latin-Squares design was completed at Point Pelee National Park over the course of five months. Systematic soil sampling and analyses provided DDT, DDE and DDD concentrations throughout the remediation experiment in order to assess the removal efficiency of hydroxypropyl-ß-cyclodextrin. In-Situ volumetric moisture content was monitored throughout the study with a TDR based system. Systematic soil sampling and analyses at the conclusion of the study provided water content, organic matter content, bulk density, porosity, hydraulic conductivity as well as sampling with depth. The application of a hydroxypropyl-ß-cyclodextrin solution did result in a substantial decrease of the concentrations of DDT, DDE and DDD from the surface soil at Point Pelee National Park. By the end of the experiment, the concentration of DDD was consistently below the regulatory limits set by the Ontario Ministry of Environment and Energy for Parkland/Recreational Land-Use. In addition to the observed decrease in concentration, there was a decrease in the degree of variation between the measured concentrations, transport of the mass of DDT, DDE and DDD to depth and an observed tailing effect at late-times. There were also fundamental changes to the system due to the application of the cyclodextrin (HPCD) solution including an increase in moisture content and organic matter, a decrease in infiltration and a corresponding decrease in field saturated hydraulic conductivity. There was no appreciable benefit of the application of a high concentration solution over a low concentration solution due to an observed "clogging" -effect. The results of this study indicates that further research is necessary to determine the extent of vertical mobilization of DDT, DDE and DDD to groundwater and the role of biological matter in the observed fundamental changes responsible for the "clogging" -effect.</p> / Thesis / Master of Science (MSc)

Made available in DSpace on 2017-07-21T14:19:31Z (GMT). No. of bitstreams: 1 MIKAMI, M M.pdf: 3402794 bytes, checksum: cb934aeb85ce1c45338450c4767a924d (MD5) Previous issue date: 2017-03-06 / The use of remotely piloted aircrafts (RPA) in precision agriculture (PA) is constantly evolving being a process comprised of the following steps: objective determination, capture and processing of images and the analisys of the obtained data. Although there is software and hardware made for those steps, the challange remains being the integration of the collected data, its reliability, and the intepretation of the resulting data for decision making. This work proposes a software architeture to make use of RPA on PA, allowing to perform all steps of the process using the Domain-Driven Design and Command and Query Responsability Segregation architectural patterns. The architecture, when used by researchers, allows the integration of new image processing modules, making use of case-based reasoning (CBR) for its evaluation. The architecture was evaluated in a case study under the following aspects: the reliability of the image processing methods and the adequacy of the CBR method when determining the best image processing algorithm for the specified objective. The results of the image processing algorithm for estimate the Normalized Difference Vegetation Index (NDVI) were compared to the results obtained by the field equipment (Greenseeker) and by processing made with the Pix4D software. Both the software and the equipment produced similar results, with a difference of about 7%. When doing the simulation for the best algorithm to be automaticaly used by the end user, the software correctly selected the algorithm with the highest probability of generating a correct outcome. In addition to the technical benefits, the developed architecture allows the results of field experiments analysis, associated with the algorithms used, to feed the knowledge base of the software so that it generates better parametrizations in the executions made by the end user. In addition to the technical benefits, the developed architecture allows the results of field experiments, associated with the used algorithms, to feed the knowledge base of the softwares that it generates better parametrizations when executed by the end user. The developed architecture in this work made possible integrating the several steps when using RPAs in PA, making easier its use by resaerchers and end users. The joint use by researchers and end users in the same environment could be an interesting alterative to publish new and better methods for image processing, giving to the end users more reliable results and more information about the crops. / O uso de aeronaves remotamente pilotadas (RPA) na agricultura de precisão (AP) está em constante evolução, sendo um processo que compreende as etapas de: determinação do objetivo, captura e processamento das imagens, e análise dos dados obtidos. Apesar de existirem alguns softwares e hardwares para essas etapas, a dificuldade ainda reside na integração dos dados coletados, sua confiabilidade, e na interpretação das informações resultantes para tomada de decisão. Este trabalho propõe uma arquitetura de software para o uso de RPA na AP que permite a execução de todas as etapas do processo utilizando os padrões arquiteturais Domain-Driven Design e Command e Query Responsability Segregation. Esta arquitetura, quando utilizada por pesquisadores, permite a integração de novos módulos de processamento de imagem, utilizando raciocínio baseado em casos (RBC) para sua avaliação. A arquitetura foi avaliada em um estudo de caso sob os seguintes aspectos: a confiabilidade dos métodos de processamento de imagem implementados e a adequação do método de RBC ao determinar o melhor algoritmo de processamento de imagem para objetivos específicos. O resultado do algoritmo de processamento de imagem para estimativa do índice de vegetação por diferença normalizada (NDVI) foi comparado aos resultados obtidos em equipamento de campo (Greenseeker) e pelo processamento via software Pix4D. Foi verificado que tanto os softwares quanto o equipamento geraram valores similares, com diferença média de 7%. Nas simulações de escolha do melhor algoritmo a ser utilizado automaticamente pelo usuário final, o software selecionou o algoritmo correto indicando para o mesmo a maior probabilidade de acerto. Além dos benefícios técnicos, a arquitetura desenvolvida permite que resultados de análises de experimentos em campo, associados aos algoritmos utilizados, alimentem a base de conhecimento do software para que o mesmo gere melhores parametrizações nas execuções feitas pelo usuário final. A arquitetura desenvolvida neste trabalho permitiu a integração das diversas etapas que envolvem o uso de RPA na AP, facilitando o uso por pesquisadores e usuários finais. A utilização conjunta de pesquisadores e usuários finais em um mesmo ambiente, pode ser uma alternativa interessante para publicação de novos e melhores métodos de processamento de imagem, fornecendo aos usuários finais mais informações sobre sua cultura e resultados mais confiáveis.

This thesis describes a methodology for expressing the consumption of drugs, a system of ATC/DDD, ATC classification and DDD recommended daily dose assigment. It also describes the data source which are relevant for this expression. In this thesis I will focuse on combined oral contraception and its consumption which I will express in DDD/1000inhab/day, number of packages and in financial expression in czech krones. At the end of this thesis I will evaluate the results of the consumption according State institute for drug control and my own survey.

Depersonalization-Derealization Disorder (DDD) is a dissociative syndrome characterized by a sense of disconnectedness from one’s own self and the world around. People suffering from the condition report feeling like external observers, cut off from their own bodies, emotions and thoughts; their surroundings are perceived as unreal. The present thesis analyses DDD by sustaining the view that its phenomenology can be understood through Metzinger’s notion of phenomenal transparency. This idea is not entirely new: recent contributions (Ciaunica et al., 2020; Ciaunica et al., 2021; Seth et al., 2012) have framed the dramatic experiences of depersonalization and derealization as instances of highly opaque mental states. However, more detailed discussions of phenomenal transparency are sparse. My contribution wishes to partially fill in this gap. To elucidate the concept of transparency, I will first highlight the distinction between the classical representationalist notion of transparency and the metzingerian, phenomenal account of it. I will then argue that phenomenal transparency adequately describes the associated depersonalized phenomenology. Finally, I will attempt to present and dissipate ambiguities contained in the concept and address potential criticism regarding the redundancy of transparency as an explanatory tool for dissociative phenomena. / Depersonalisations- och Derealisationssyndrom (DDD) är ett dissociativt syndrom som kännetecknas av en känsla av att vara frånkopplad från ens eget jag och omvärlden. Människor som lider av tillståndet rapporterar att de känner sig som externa observatörer, avskurna från sina egna kroppar, känslor och tankar; deras omgivning upplevs som overklig. Denna avhandling analyserar DDD genom att stödja uppfattningen att dess fenomenologi kan förstås genom Metzingers föreställning om fenomenal transparens. Denna idé är inte helt ny: senaste bidrag (Ciaunica et al., 2020; Ciaunica et al., 2021; Seth et al., 2012) har ramat in de dramatiska upplevelserna av depersonalisering och derealisering som förekomster av mycket ogenomskinliga mentala tillstånd. Mer detaljerade diskussioner om fenomenal transparens är dock sparsamma. Mitt bidrag vill delvis fylla denna lucka. För att belysa begreppet transparens kommer jag först att lyfta fram distinktionen mellan den klassiska representationalistiska föreställningen om transparens och den metzingerska, fenomenala redogörelsen för den. Jag kommer då att hävda att fenomenal transparens på ett adekvat sätt beskriver den associerade depersonaliserade fenomenologin. Slutligen kommer jag att försöka presentera och skingra oklarheter som finns i konceptet och ta upp potentiell kritik angående transparensens redundans som ett förklarande verktyg för dissociativa fenomen.

This thesis focuses on the effects of slip-slip, slip-twin, and slip-precipitates interactions on strain hardening, with the intent of developing comprehensive modelling capabilities enabling to investigate unit processes and their collective effects up to the macroscopic response. To this end, the modelling strategy adopted in this work relies on a two-way exchange of information between predictions obtained by discrete dislocation dynamics (DDD) simulations and crystal plasticity laws informed by DDD. At the scale of lattice defects, a DDD tool enabling simulations on any crystalline structure is developed to model dislocation-dislocation, dislocation-twin and dislocation-particles interactions. The tool is first used to quantify the collective effect and strength of dislocation-dislocation interactions on latent-hardening, especially in the case of pure Mg. With regards to slip-twin interactions, a transmission mechanism is implemented in the DDD framework so as to investigate the collective effects of dislocation transmission across a twin-boundary. With respect to slip-particles interactions, an efficient novel DDD approach based on a Fast Fourier Transform (FFT) technique is developed to include the field fluctuations related to elastic heterogeneities giving rise to image forces on dislocation lines. In addition, the DDD-FFT approach allows for the efficient treatment of anisotropic elasticity, thereby paving the way towards performing DDD simulations in low-symmetry polycrystals. The information extracted from the collective dislocation interactions are then passed to a series of constitutive models, and later used to quantify their effects at the scale of the polycrystal. For such purpose, a constitutive framework capable of receiving information from lower scales and establishing a direct connection with DDD simulations is notably developed.

Magister Public Health - MPH / Background Antibiotic resistance is a phenomenon that occurs naturally and is accelerated by use. There have been no studies looking at trends in antibiotic consumption in the public health sector in Namibia, which provides services to 85% of the population. Aim This study described the pattern of antibiotic consumption in the Namibian public health sector based on distribution of antibiotics from Central Medical Stores (CMS) to the 13 regions in the country. Methodology Antibiotic consumption data from distribution records at the Central Medical Store (CMS), public health sector wholesaler, between 1 January 2010 and 31 December 2016 was collated and analysed to describe trends and usage patterns in the public health sector of Namibia. For the purpose of this study DDD per 1000 inhabitants per day (DID) was used as an indicator so as to be comparable with previously conducted studies. DIDs provide information about the proportion of the selected population using a particular medicine per day. The World Health Organization (WHO) recommended anatomical therapeutic classification (ATC)/daily defined dose (DDD) methodology be used to analyse the data and evaluate the consumption. Data was presented using stacked bar charts to demonstrate the variation in consumption by ATC classes in each region and over time.

DDT was extensively and globally used as a pesticide in agriculture and for malaria vector control from the 1940’s until the 1970’s. Due to its heavy use, DDT became ubiquitously distributed throughout the environment. DDT and several DDT metabolites are persistent organic pollutants. Two DDT metabolites, 3-MeSO2-DDE and o,p’-DDD have been proved to be tissue specific toxicants in the adrenal cortex. They are bioactivated to reactive intermediates which bind covalently to the adrenal cortex causing cell death. Due to its tissue specific toxicity o,p’-DDD has been used as a chemotherapy drug for adrenal cancer in humans. The efficacy and potency is however low and o,p’-DDD treatment is associated with serious side effects. 3-MeSO2-DDE has been suggested as a potential alternative therapeutic agent. A key aim of this thesis has been to improve the understanding of the kinetics of the two adrenocorticolytic compounds o,p’-DDD, its two enantiomers and 3-MeSO2-DDE. To meet this objective chemical synthesis and enantioselective analysis were required. Furthermore, in vitro toxicity of o,p’-DDD enantiomers and diastereomers were performed. An 11 step synthesis of 3-SH-DDE has been developed to promote both labelled and unlabelled synthesis of 3-alkylsulfonyl-DDE. Toxicokinetic studies showed that 3-MeSO2-DDE and o,p’-DDD were accumulated in tissues and retained in adipose tissue in minipigs. 3-MeSO2-DDE however had a twice as long biological t1/2 and a considerably lower Vd compared to o,p’-DDD. Suckling offspring were more exposed to 3-MeSO2-DDE than their mothers who were given 3-MeSO2-DDE orally. Interindividual differences in enantiomer kinetics in minipigs were observed suggesting polymorphism among the minipigs. Preparative isolation of the o,p’-DDD enantiomers is presented allowing determination of the absolute structures of the o,p’-DDD enantiomers by X-ray. The pure enantiomer of o,p’-DDD showed significant differences in toxicity in human adrenocortical cells.

The aim with this thesis has been to make a survey of radiation hardened electronics, explaining why and how radiation affects electronics and what can be done to harden it. The effects radiation have on electronics in general and in specific commonly used devices are explained qualitatively. The effects are divided into Displacement Damage (DD), Total Ionizing Dose (TID) and Single Event Effects (SEEs). The devices explained are MOSFETs, Silicon On Insulator (SOI) transistors, 3D-transistors, Power transistors, Optocouplers, Field Programmable Gate Arrays (FPGAs), three dimensional circuits (3D-ICs) and Flash memories. Different radiation hardening by design (RHBD) techniques used to reduce or to remove the negative effects radiation induces in electronics are also explained. The techniques are Annular transistors, Enclosed source/drain transistors, Guard rings, Triple Modular Redundancy (TMR), Dual Interlocked Storage Cells (DICE), Guard gates, Temporal filtering,Multiple drive, Charge dissipation, Differential Charge Cancellation (DCC), Scrubbing, Lockstep, EDAC codes and Watchdog timers.