Made available in DSpace on 2016-08-29T15:08:57Z (GMT). No. of bitstreams: 1 tese_7549_Dissertação - Ana Regina Seno.pdf: 1543901 bytes, checksum: d93c6bde53203cf847845393454409d4 (MD5) Previous issue date: 2014-03-10 / Este estudo propõe-se a analisar o discurso político de voz feminina, pela pers-pectiva da Análise do Discurso (AD) de linha francesa, a partir da escolha de quatro discursos proferidos pela presidente brasileira Dilma Rousseff, utilizan-do-se das contribuições trazidas por Domi¬nique Maingueneau e Patrick Charaudeau. O eixo dessa pesquisa está no exame do ethos discursivo segundo as noções apresentadas pelos dois estudiosos, para a identificação das características de discurso político proferido por enunciador de voz feminina. Dos estudos de Maingueneau, além da categoria de ethos discur-sivo, são utilizadas as categorias de interdiscurso e de cenas de enuncia¬ção, especialmente as cenografias constituídas nos discursos políticos escolhidos. Das pesquisas semiolinguísticas de Charaudeau, privilegiamos as noções de ethos, de carisma e de pathos aplicadas ao discurso polí¬tico, buscando caracterizar a maneira de ser e de dizer do sujeito enunciador, revelada pela patemização discursiva. Embora os dois pesqui¬sadores tenham propostas teórico-metodológicas basilares diferentes, busca-se encontrar os pontos de com¬plementação de abordagens para a caracterização do ethos discur¬sivo de voz feminina. Os procedimentos de análises são precedidos por breve histórico do percurso, da participação e da presença da mulher na política nacional e internacional, principalmente nos séculos XX e XXI, a fim de compor o cenário histórico-social atual, uma vez que há o fato inédito e relevante de uma mulher tornar-se a primeira presidente do Brasil. As principais discussões realizadas neste estudo giram em torno aos macrotemas e microtemas dos discursos selecionados, suas cenografias ali constituídas, destacando as marcas, que influem na caracterização de ethos, incluindo aquelas propostas por Charaudeau, tais como, de autoridade, de credibilidade, de seriedade e de co-ragem. Associado a esses aspectos que ajudam a carac¬terizar o ethos, são analisados também os elementos constituintes da memória discursiva, articulando-os com as formações discursivas inerentes aos campos discursivos aos quais pertencem. Por fim, realiza-se uma síntese das análises empreendidas e conclui-se com o detalhamento da repercus¬são observada na imagem da mulher na política, discorrendo-se sobre ethos de enunciador de voz feminina em discurso político.

This thesis is made up of three parts: i) the development of a comprehensive computational model of the pulmonary (patho)physiology of healthy and diseased lungs, ii) the application of a novel optimisation-based approach to validate this computational model, and iii) the use of this model to optimise mechanical ventilator settings for patients with diseased lungs. The model described in this thesis is an extended implementation of the Nottingham Physiological Simulator (NPS) in MATLAB. An iterative multi-compartmental modelling approach is adopted, and modifications (based on physiological mechanisms) are proposed to characterise healthy as well as diseased states. In the second part of the thesis, an optimisation-based approach is employed to validate the robustness of this model. The model is subjected to simultaneous variations in the values of multiple physiologically relevant uncertain parameters with respect to a set of specified performance criteria, based on expected levels of variation in arterial blood gas values found in the patient population. Performance criteria are evaluated using computer simulations. Local and global optimisation algorithms are employed to search for the worst-case parameter combination that could cause the model outputs to deviate from their expected range of operation, i.e. violate the specified model performance criteria. The optimisation-based analysis is proposed as a useful complement to current statistical model validation techniques, which are reliant on matching data from in vitro and in vivo studies. The last section of the thesis considers the problem of optimising settings of mechanical ventilation in an Intensive Therapy Unit (ITU) for patients with diseased lungs. This is a challenging task for physicians who have to select appropriate mechanical ventilator settings to satisfy multiple, sometimes conflicting, objectives including i) maintaining adequate oxygenation, ii) maintaining adequate carbon dioxide clearance and iii) minimising the risks of ventilator associated lung injury (VALI). Currently, physicians are reliant on guidelines based on previous experience and recommendations from a very limited number of in vivo studies which, by their very nature, cannot form the basis of personalised, disease-specific treatment protocols. This thesis formulates the choice of ventilator settings as a constrained multi-objective optimisation problem, which is solved using a hybrid optimisation algorithm and a validated physiological simulation model, to optimise the settings of mechanical ventilation for a healthy lung and for several pulmonary disease cases. The optimal settings are shown to satisfy the conflicting clinical objectives, to improve the ventilation perfusion matching within the lung, and, crucially, to be disease-specific.

Listeria monocytogenes est un pathogène intracellulaire facultatif responsable d’une infection sévère d’origine alimentaire, la listériose. L’étude du processus d’infection cellulaire de cette bactérie a permis d’élucider divers mécanismes impliqués dans les interactions hôte-pathogène et dans le fonctionnement de la cellule eucaryote. En particulier, L. monocytogenes a été l’un des modèles pionniers dans la découverte du ciblage de la chromatine et de régulateurs nucléaires par des microbes. L’étude d’un facteur de virulence de L. monocytogenes, LntA, a permis l’identification d’un de ces régulateurs : BAHD1. En recrutant des protéines impliquées dans la formation de l’hétérochromatine, telles HDAC1/2 et HP1, BAHD1 stimule la formation d’une chromatine compacte à effet répressif. Lors d’une infection de cellules épithéliales par L. monocytogenes, BAHD1 réprime la réponse immunitaire stimulée par les interférons, une fonction inhibée par LntA. BAHD1 demeurant peu étudiée, mon doctorat a eu pour premier objectif de poursuivre la caractérisation de ce régulateur épigénétique. Par ailleurs, des données préliminaires suggéraient qu’un facteur de virulence de Listeria récemment découvert, InlP, avait la potentialité d’être, comme LntA, une nucléomoduline. Mon deuxième objectif a été d’explorer cette hypothèse.Les résultats de mon premier axe montrent que BAHD1 interagit avec MIER1 et que cette interaction est cruciale pour l’association de BAHD1 aux HDAC1/2. Nous reportons également que BAHD1 modifie la chromatine en changement la méthylation et l’acétylation des histones, ainsi que la méthylation de l’ADN, au niveau d’un gène cible, ESR1. Ces résultats nous permettent de proposer que BAHD1 forme, avec MIER1, un échafaudage assemblant un nouveau complexe de remodelage de la chromatine associé aux HDAC1/2 : le complexe BAHD1. Nous avons ensuite étudié un rôle de BAHD1 dans un organe ciblé par la Listeria, le cerveau. Nos résultats indiquent qu’une déficience totale en BAHD1 altère le transcriptome global de cet organe chez la souris. Les gènes majoritairement surexprimés sont impliqués dans des fonctions du système nerveux, le métabolisme et des troubles neurologiques. Les gènes majoritairement sous-exprimés sont impliqués dans des voies de l’immunité innée, dont des gènes de réponses aux interférons. Par ailleurs, une haplo-déficience en Bahd1 provoque des troubles comportementaux. En comparaison des souris Bahd1+/+, les souris Bahd1+/- souffrent d’une anxiété accrue et d’altérations du réflex de sursaut acoustique. Ces résultats suggèrent qu’une dérégulation de BAHD1, par des stimuli de l’environnement ou par des stimuli infectieux, pourrait avoir des effets neuro-pathologiques.Le second axe de ma thèse concernait l’étude des interactions d’InlP avec des protéines nucléaires de l’hôte, identifiées par un crible double-hybride. Nous montrons d’abord qu’InlP est une internaline atypique, avec des répétitions riches en leucine caractérisées par un motif LPX2. Nous identifions, ensuite, deux protéines nucléaires ciblées par InlP : le facteur d’épissage et suppresseur de tumeur RBM5 et le corépresseur RERE. Quand InlP est produite de façon ectopique dans les cellules humaines, elle se localise dans le noyau, où elle altère la formation de corps nucléaires enrichis en RERE. Dans des cellules sur-exprimant RBM5, InlP inhibe l’effet pro-apoptotique de RBM5 et stimule la formation de corps nucléaires denses associés à RBM5. Ces résultats suggèrent qu’InlP est une nucléomoduline agissant sur la l’assemblage et le désassemblage de compartiments de stockage de protéines cibles impliquées dans la synthèse et l’épissage d’ARNs de l’hôte.Ce travail ouvrent des perspectives dans la compréhension des interactions hôte-pathogène et dans une meilleure connaissance des mécanismes patho-épigénétiques, ainsi qu’en biologie cellulaire, dans la compréhension de la dynamique des organites nucléaires sans membrane. / Listeria monocytogenes is an optional intracellular pathogen responsible for a severe foodborne infection called listeriosis. The study of the cellular infection process of this bacterium has shed light on various mechanisms involved in host-pathogen interactions and in the functioning of the eukaryotic cell. In particular, L. monocytogenes has emerged as one of the pioneering models in the discovery of microbial targeting of chromatin and nuclear regulators. The study of a virulence factor of L. monocytogenes, LntA, allowed the identification of one of these regulators : BAHD1. By recruiting proteins involved in the formation of heterochromatin, such as HDAC1/2 and HP1, BAHD1 stimulates the formation of a compact chromatin with a repressive effect. When epithelial cells are infected with L. monocytogenes, BAHD1 suppresses the immune response stimulated by interferons, a function inhibited by LntA. Since BAHD1 is still under-researched, the first objective for my thesis was to further characterize this epigenetic regulator. In addition, preliminary data suggested that a recently discovered virulence factor of Listeria, InlP, had the potential to be, like LntA, a nucleomodulin. My second objective was to explore this hypothesis.The results of my first axis show that BAHD1 interacts with MIER1 and that this interaction is crucial for the association of BAHD1 with HDAC1/2. We also report that BAHD1 modifies chromatin by changing histone methylation and acetylation, as well as DNA methylation, at a target gene, ESR1. These results allow us to propose that BAHD1 form, with MIER1, a scaffold assembling a new chromatin remodeling complex associated with HDAC1/2 : the BAHD1 complex. We then studied the role of BAHD1 in an organ targeted by Listeria, the brain. Our results indicate that a total deficiency in BAHD1 alters the overall transcriptome of this organ in mice. Most of the overexpressed genes are involved in nervous system functions, metabolism and neurological disorders. The predominantly downregulated genes are involved in innate immunity pathways, including interferon response genes. In addition, a haplodeficiency in Bahd1 causes behavioral problems. Compared to Bahd1+/+ mice, Bahd1+/- mice suffer from increased anxiety and changes in acoustic startle reflex. These results suggest that deregulation of BAHD1, through environmental or infectious stimuli, may have neuro-pathological effects.The second axis of my thesis focused on the study of InlP interactions with host nuclear proteins, identified by a double-hybrid screen. First, we show that InlP is an atypical internalin, with leucine-rich repeats characterized by an LPX2 motif. We then identify two nuclear proteins targeted by InlP: the splicing factor and tumor suppressor RBM5 and the corepressor RERE. When InlP is produced ectopically in human cells, it is localized in the nucleus, where it alters the formation of nuclear bodies enriched in RERE. In RBM5-overexpressing cells, InlP inhibits the pro-apoptotic effect of RBM5 and stimulates the formation of dense nuclear bodies associated with RBM5. These results suggest that InlP is a nucleomodulin acting on the assembly and disassembly of target protein storage compartments involved in the synthesis and splicing of host RNAs.This work opens perspectives in the understanding of host-pathogen interactions and in a better knowledge of patho-epigenetic mechanisms, as well as in cell biology and the understanding of membraneless nuclear organelles dynamics.

La dystrophie facioscapulohumérale (FSHD) est une dystrophie musculaire autosomique dominante, dégénérative et progressive. Les traitements élaborés jusqu'à présent n'ont pas réussi à améliorer le quotidien des patients FSHD. Plusieurs études se sont focalisées sur les mécanismes moléculaires de cette pathologie, néanmoins plusieurs d'entre elles sont contradictoires. La vision actuelle de la FSHD est celle d'une pathologie due à un mécanisme épigénétique complexe et les mécanismes moléculaires responsables de cette pathologie sont encore mal connus. Plusieurs analyses comparatives des profils d'expression des ARNm et des protéines de muscles de patients atteints de FSHD et de contrôles ont permis de montrer que plusieurs gènes impliqués dans le stress oxydant sont dérégulés de façon spécifique dans les muscles FSHD. Nos travaux ont permis de montrer dans la FSHD, aussi bien au niveau systémique, musculaire et cellulaire (cultures primaires musculaires) une augmentation des dommages oxydatifs qui se traduisent par une augmentation des peroxydes lipidiques et protéines oxydées, associés à une altération des défenses antioxydantes. Ce stress oxydant dans les biopsies musculaires et cultures primaires musculaires est associé à un dysfonctionnement mitochondrial. Des analyses plus fines sur l'action des espèces réactives de l'oxygène et leurs sources pourraient contribuer à une meilleure compréhension des bases physiopathologiques de la FSHD et permettre la sélection de thérapeutiques adaptées aux anomalies des patients FSHD. / Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal inherited muscular dystrophy. Actually no treatment led to improve the quality of life. Many studies have been focused on the molecular mechanisms of this disease, several of them were contradictory. The present view of the FSHD seems to be due to a complex epigenetic mechanism. Actually, no gene has been identified. Several comparative studies permit the identification of many genes involved in oxidative stress, deregulated in FSHD myoblasts and biopsies in comparison to healthy ones. Analysis of oxidative stress markers show that patients with FSHD present increased oxidative damage in blood as well as in biopsy muscle and muscular primary cell culture associated with altered antioxidant enzyme defenses. Oxidative stress is also associated with mitochondrial dysfunction. Complementary studies focusing in pathway of reactive oxygen species would contribute to a better understanding of pathophysiological bases of FSHD in order to establish a very helpful therapeutics for FSHD patients.

Systematic characterization of microbes in several tumors including colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC) has revealed the presence of multiple species of intracellular bacteria within tumors. However, there is limited knowledge on how these bacteria colonize tumors, how they survive inside host cells, how they modulate host cell phenotypes, and if their elimination should complement cancer therapy. This is, in part, due to the lack of representative animal models, challenges in co-culture of host epithelial cells and bacteria, and limited resolution of available analytical techniques to study host-microbial interactions. I have addressed these challenges by harnessing multiple technologies from microbiology, genetic engineering, tissue engineering, and microfluidics, in order to investigate the role of an emerging oncomicrobe, Fusobacterium nucleatum, in the tumor microenvironment (TME). F. nucleatum is a Gram-negative, anaerobic bacterium that is normally found within the oral cavity. However, its selective enrichment in CRC and PDAC tumors is correlated with poor clinical outcomes. My work along with collaborators in the Verbridge, Slade, and Lu labs at Virginia Tech has revealed a multifactorial impact of F. nucleatum in influencing cancer progression. First, in CRC, we discovered that F. nucleatum infection of host cancer cells induced robust secretion of select cytokines that increased cancer cell migration, impacted cell seeding, and enhanced immune cell recruitment. In PDAC, we uncovered additional cytokines that were secreted from both normal and cancerous pancreatic cell lines upon infection with F. nucleatum that increased cancer cell proliferation and migration via paracrine and autocrine signaling, notably in the absence of immune cell participation. In order to examine the contribution of a hypoxic TME on infection dynamics, we used a multi-omics approach that combined RNA-seq and ChIP-seq of H3K27ac to determine epigenomic and transcriptomic alterations sustained within hypoxic CRC cells upon infection with F. nucleatum. Our findings revealed that F. nucleatum can subvert host cell recognition in hypoxia and can modulate the expression of multiple cancer-related genes to drive malignant transformation. Insights gained from this research will pave the way for future studies on the impact of the tumor microbiome in cancer and will identify novel targets for therapy and clinical intervention to control bacteria-induced exacerbation of cancer. / Doctor of Philosophy / Colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC) are the second and third leading causes of cancer death in the United States, respectively. Recent systematic characterization of various tumor types revealed the presence of distinct bacteria within tumors. However, there is limited knowledge on how these bacteria colonize tumors, how they survive inside host cells, how they modulate host cell phenotypes, and if their elimination should complement cancer therapy. This is, in part, due to the lack of representative animal models, challenges in developing host cell-microbe co-culture models, and limited resolution of available analytical techniques to study host-microbial interactions. I have addressed these challenges by harnessing multiple technologies from microbiology, genetic engineering, tissue engineering, and microfluidics, in order to investigate the role of an emerging cancer-associated microbe, Fusobacterium nucleatum, in the tumor microenvironment (TME). F. nucleatum is a microbe commonly found within the oral cavity. However, clinical studies revealed that selective enrichment of F. nucleatum in CRC and PDAC tumors significantly correlated with poor prognosis. My work along with collaborators in the Verbridge, Slade, and Lu labs at Virginia Tech has revealed a multifactorial impact of F. nucleatum in influencing cancer progression. First, in CRC, we discovered that F. nucleatum invasion of host cancer cells induced the secretion of select proteins called cytokines that cells use to signal and communicate with each other. These cytokines directly stimulated the cell migration of host cancer cells which is usually associated with increased cancer aggressiveness. In PDAC, F. nucleatum infection induced the secretion of additional cytokines from both cancer cells and normal cells that, in addition to cell migration, impacted the proliferation of cancer cells, another feature of aggressive cancers. F. nucleatum usually thrives in a low oxygen environment that is prevalent in cancer tissue and hence, we examined how a low oxygen environment can influence infection dynamics using sequencing technologies that probe the genomic constitution within cells. Our findings revealed that F. nucleatum can escape recognition in low oxygen environments and can modulate the expression of multiple cancer-related programs within the cell to drive cancer progression. Insights gained from this research will pave the way for future studies on the impact of the tumor-associated microbes in cancer and will identify novel targets for therapy and clinical intervention to control bacteria-induced exacerbation of cancer.

Thesis (MScMedSc)--Stellenbosch University, 2013. / ENGLISH ABSTRACT: Left ventricular hypertrophy (LVH) occurs when the cardiomyocytes in the left ventricle become enlarged by increasing in mass in response to haemodynamic pressure overload. This can either be attributed to a normal physiological response to exercise or can be the result of a maladaptive process or disease state, such as chronic hypertension. Hypertrophic cardiomyopathy (HCM) is the most common form of Mendelian-inherited cardiac disease. A defining characteristic thereof is primary LVH that occurs when there are no other hypertrophy-predisposing conditions present. Therefore, HCM provides a unique opportunity to study the molecular determinants of LVH in the context of a Mendelian disorder, instead of in more complex disorders such as hypertension. Over 1000 HCM-causing mutations in 19 genes have been identified thus far, most of them encoding sarcomeric proteins residing in the sarcomeric C-zone. However, for many HCM patients no disease-causing genes have been identified. Moreover, studies have shown phenotypic variation in presentation of disease in, as well as between, families in which the same HCM-causing mutation segregates. This has led many investigators to conclude that genetic modifiers of hypertrophy exist. The aim of the study was to identify novel plausible HCM-causing or modifier genes by searching for interactors of a known HCM-causing protein, namely titin. The hypothesis was that genes encoding proteins, which interact with proteins that are encoded by known HCM-causative genes, may also be considered HCM-causing or may modify the HCM phenotype. To this end, the aim was to identify novel interactors of the 11-domain super-repeat region of titin, which resides within the sarcomeric C-zone, using yeast two-hybrid analysis. Five putative interactors of the 11-domain super-repeat region of titin were identified in this study. These interactions were subsequently verified by colocalisation in H9C2 rat cardiomyocytes, providing further evidence for possible interactions between titin and these proteins. The putative interactor proteins of titin determined from the Y2H library screen were: filamin C (FLNC), phosphatidylethanolamine-binding protein 4 (PEBP4), heart-type fatty acid binding protein 3 (H-FABP3), myomesin 2 (MYOM2) and myomesin 1 (MYOM1). The FLNC gene could be a candidate for cardiac diseases, especially cardiomyopathies that are associated with hypertrophy or developmental defects. The putative interaction of titin and PEBP4 is speculated to be indicative of the formation of the interstitial fibrosis and myocyte disarray seen in HCM. Heart-type fatty acid-binding protein 3 has prognostic value to predict recurrent cardiac events. Its suggested interaction with titin is speculated to play a role in inhibiting its functional abilities. Myomesin 2 is jointly responsible, with MYOM1, for the formation of a head structure on one end of the titin string that connects the Z and M bands of the sarcomere. This is speculated to be linked to a developmental error with the result being a defect in sarcomeric structure formation, which could result in pathologies such as HCM. Therefore, these identified proteins could likely play a functional role in HCM due to their interactions with titin. This research could thus help with new insights into the further understanding of HCM patho-aetiology. / AFRIKAANSE OPSOMMING: Linker ventrikulêre hipertrofie (LVH) ontstaan wanneer die kardiomyosiete in die linkerventrikel vergroot as gevolg van 'n verhoging in massa in reaksie op hemodinamiese drukoorlading. Dit kan toegeskryf word aan 'n normale fisiologiese respons op oefening of kan die gevolg wees van 'n wanaangepaste of siektetoestand, soos chroniese hipertensie. Hipertrofiese kardiomiopatie (HKM) is die mees algemene vorm van Mendeliese oorerflike hartsiekte. 'n Bepalende eienskap daarvan is primêre LVH, wat plaasvind wanneer daar geen ander hipertrofie-predisponerende voorwaardes teenwoordig is nie. Gevolglik bied HKM 'n unieke geleentheid om die molekulêre derterminante van LVH te bestudeer, in die konteks van 'n Mendeliese oorerflike siekte, in plaas van om dit in die meer komplekse siektes soos hoë bloeddruk te bestudeer. Meer as 1000 HKM-veroorsakende mutasies is tot dusver in 19 gene geïdentifiseer. Die meeste van hulle kodeer vir sarkomeriese proteïene wat in die C-sone voorkom. Egter, vir baie HKM-pasiënte is geen siekte-veroorsakende gene al geïdentifiseer nie. Daarbenewens het studies getoon dat variasie in fenotipiese aanbieding van die siekte in, sowel as tussen, families voorkom wat dieselfde HKM-veroorsakende mutasie het. Dit het daartoe gelei dat baie navorsers tot die gevolgtrekking gekom het dat genetiese wysigers van hipertrofie wel bestaan. Die doel van die studie was om nuwe moontlike HKM-veroorsakende of wysiger-gene te identifiseer deur te soek vir interaktors van 'n bekende HKM-veroorsakende proteïen, naamlik titin. Die hipotese was dat gene wat vir proteïene kodeer, wat in wisselwerking is met proteïene wat geïnkripteer word deur bekende HKM-veroorsakende gene, ook oorweeg kan word om HKM te veroorsaak. Dit kan ook die HKM fenotipe verander. Dus was die doel om nuwe interaktors van die 11-domein super-herhaalstreek van titin, soos gevind binne die sarkomeriese C-sone, te identifiseer deur middel van gis-twee-hibried-analise. Vyf vermeende interaktors van die 11-domein super-herhaalstreek van titin is in hierdie studie geïdentifiseer. Hierdie interaksies is later geverifieer met behulp van ko-lokalisering in H9C2-rotkardiomyosiete, wat verdere bewyse vir moontlike interaksies tussen titin en hierdie proteïene verskaf. Die vermeende interaktor-proteïene van titin wat bepaal is vanaf die gis-twee-hibried-biblioteeksifting was as volg: filamin C (FLNC), phosphatidylethanolamine-bindingsproteïen 4 (PEBP4), hart-tipe-vetsuur bindingsproteïen 3 (H-FABP3), myomesin 2 (MYOM2) en myomesin 1 (MYOM1). Die FLNC-geen kan 'n kandidaat vir kardiale siektes, veral kardiomiopatieë, wees wat geassosieer word met hipertrofie of ontwikkelingsafwykings. Die vermeende interaksie van titin en PEBP4 dui daarop om 'n aanduiding te wees vir die vorming van die interstisiële fibrose en miokardiale wanorde, soos gesien in HKM. Hart-tipe-vetsuur bindingsproteïen 3 het prognostiese waarde om herhalende kardiale gebeure te voorspel. Verder dui sy voorgestelde interaksie met titin moontlik daarop dat dit 'n rol kan speel in die inhibering van sy funksionele vermoëns. Myomesin 2 tesame met MYOM1 is verantwoordelik vir die vorming van 'n kopstruktuur aan die een kant van die titinstring wat dan die Z- en M-bande van die sarkomeer verbind. Daar word vermoed dat dit gekoppel is aan 'n ontwikkelingsfout, met die gevolg dat daar 'n defek is in sarkomeriese struktuurvorming, wat weer kan lei tot patologieë soos HKM. / Mrs Wendy Ackerman / Prof Paul van Helden / National Research Foundation (NRF) / Stellenbosch University

The goal of the thesis "The economic and social aspects of casinos and slot machines in the border areas" was to design an economically and socially beneficial policy towards gaming rooms and casinos in the area of the town Cheb. The work is divided into several parts. The first part deals with the experience of economic and social aspects of casinos and slot machines. In the practical part is described the situation of casinos, slot machines and gaming rooms in Cheb. Under the terms of economic factors of gambling was made the comparison of their incomes and expenditures, observations focused on tourism, the local multiplier calculation and proving the depending between unemployment and number of slot machines. In the section of social factors are characterized socio-pathological phenomena. In the last part there was suggested the policy for gambling in the town Cheb.