Francisella tularensis is a facultative intracellular pathogen and is the etiological agent of tularemia. One key aspect to the success of Francisella as a pathogen is ability of the organism to establish infection with a low inoculum, as few as 10 colony forming units (cfu). Essential to this process is the Francisella pathogenicity island (FPI). Several studies have been performed to understand how the FPI is regulated; however, the working model is not complete, as the signals important for regulation are unknown. Additionally, the mechanisms of the proteins MigR, TrmE, and CphA, which are important for activation of the FPI, are unknown. I initiated the study of this regulatory system by measuring the ability of various cellular stresses to activate an iglA-lacZ reporter. I identified that amino acid starvation and growth in basic pH activated expression of the reporter in both LVS and Schu S4. By combining these two stresses I was able to induce iglA-lacZ reporter expression in an additive manner. As it was previously demonstrated that ppGpp is important for stabilization of the regulatory complex that transcribes FPI genes, I demonstrated by TLC that both amino acid starvation and basic pH effected iglA-lacZ expression by increasing ppGpp. Due to the importance of ppGpp in FPI expression and because MigR, TrmE, and CphA each appear to be involved in a metabolic process: fatty acid metabolism (migR) t-RNA modification (trmE) and amino acid storage (cphA), I had hypothesized that the effect on these mutations were due to decreased levels of the small alarmone ppGpp. I compared ppGpp accumulation of LVS mutants in migR, trmE, and cphA to the parent strain and observed that loss of these genes resulted in reduced ppGpp. To better understand the importance of ppGpp synthesis in F. tularensis pathogenesis, I compared the phenotypes of these strains in primary human macrophages and two immortalized epithelial cell lines. These experiments demonstrated that although each of these strains had reduced ppGpp, there were cell line specific growth phenotypes. Mice infected with these strains survived suggesting tight regulation of the FPI is required for virulence. When similar mutations were characterized in the Schu S4 background these mutations retained their regulatory role; however, mutation of migR did not significantly decrease virulence in mice. As my data demonstrated that there are different challenges that Francisella must overcome to successfully replicate within cells, I developed an in vitro model to study the interactions of F. tularensis with human alveolar type II cells (AT-II). Interestingly, Schu S4 internalizes and replicates in these recently immortalized human AT-II cells whereas, LVS internalizes, but replicates poorly within these cells. Finally, to better understand the role of AT-II cells in vivo, I performed Transmission Electron Microscopy (TEM) of infected mice. These data confirmed that Schu S4 infected both alveolar macrophages and AT-II cells. Together, this work contributes to the understanding of how Francisella adapts to various environments by modulating virulence gene expression and highlights differences between virulent Schu S4 and LVS, which may partially contribute to virulence differences observed between strains.

South Africa has faced many changes in the last 20 years. There are some glaringly obvious ones such as democracy while others, such as the considerable increase of the legislative and regulatory requirements in the financial-services industry, are more subtle. Both however, have far-reaching consequences for both individuals and businesses. In Schaeffer's keynote address at the 2011 Financial Planning Convention, the global trends currently influencing the financial-planning profession were pointed out. These included the move towards a more relationship-based approach between financial planners and their clients, with holistic service offerings and regulatory change. Currently close to 100 000 Financial Services Board (FSB)-registered brokers/ advisors/ planners/ consultants claim to offer financial advice. Of these representatives only 4 600 (approximately) are Certified Financial Planner® professionals. The Financial Planning Institute of Southern Africa (FPI) maintains that the regulatory environment governing the financial industry is dynamic. Coupled with a tumultuous economic environment, this enforces the importance of an expert to assist individuals and businesses in planning for the future. The primary purpose of the Financial Advisory and Intermediaries Services Act (FAIS Act) is to: 1. protect the client against indecorous conduct by the financial service provider (FSP) and its representatives when providing financial advice and/or rendering intermediary services to clients; 2. ensure economic efficiency of the industry; 3. ensure that clients of FSPs are provided with sufficient information regarding their financial products, the representatives selling the products, the represented FSP and the product provider offering the products. The effect of the FAIS Act is that key individuals and representatives are now being held responsible for their actions, which may include providing incorrect information or not having sufficient qualifications or experience. According to the FSB the FAIS Fit and Proper requirements determine a set of requirements that all FSPs, key individuals and representatives need to comply with. The Determination of Fit and Proper Requirements of 2008 outlines the categories of fit and proper requirements for FSPs, their key individuals and representatives. The categories of the FAIS Fit and Proper requirements are: - honesty and integrity requirements for FSPs, key individuals and representatives; - competency requirements of FSPs, key individuals and representatives; - experience requirements of FSPs, key individuals and representatives; - qualifications requirements of key individuals and representatives; - regulatory examinations requirements of key individuals and representatives; - continuous professional development requirements of FSPs, key individuals and representatives; - operational ability of FSPs, key individuals and representatives; and - solvency of FSPs. The empirical study of the research was conducted nationally, within South Africa. The focus of the study was to investigate the perception of financial planners with regard to the regulatory and legislative prescriptions of the financial-services industry. The general objective of the study is to provide a quantitative measure of the perception of financial planners of the effect that the legislative and regulatory requirements in South Africa have on the ethicality of the financial-planning industry. To achieve this objective, the empirical study focussed on the responsibilities of financial-services providers and the FAIS fit and proper requirements as set out by the FAIS Act. The population identified for the empirical study consisted of financial planners that provide advisory and/or intermediary services in South Africa. The population of the study consisted of the full advisory complement, 826, which form part of the advisory division of a major South African financial-services provider. These financial planners are located across South Africa, in all nine provinces and in rural and metropolitan areas. Based on the result of the adjusted sample size equation, the required sample size for the study is reduced from 266 to 201. A total of 260 responses were received for the study which ensures a high level of accuracy is achieved from the findings of the research. The results of the empirical study provide ample proof that financial planners support the necessity and specificity of the FAIS fit and proper requirements as defined by the FAIS Act. Additionally, the financial planners agree that the determinants of the FAIS Act are not only beneficial to the sustainability and ethicality of the industry, but also support the success of the planner and ultimately ensure that clients receive the best possible financial advisory and/or intermediary services. / MBA, North-West University, Potchefstroom Campus, 2015

South Africa has faced many changes in the last 20 years. There are some glaringly obvious ones such as democracy while others, such as the considerable increase of the legislative and regulatory requirements in the financial-services industry, are more subtle. Both however, have far-reaching consequences for both individuals and businesses. In Schaeffer's keynote address at the 2011 Financial Planning Convention, the global trends currently influencing the financial-planning profession were pointed out. These included the move towards a more relationship-based approach between financial planners and their clients, with holistic service offerings and regulatory change. Currently close to 100 000 Financial Services Board (FSB)-registered brokers/ advisors/ planners/ consultants claim to offer financial advice. Of these representatives only 4 600 (approximately) are Certified Financial Planner® professionals. The Financial Planning Institute of Southern Africa (FPI) maintains that the regulatory environment governing the financial industry is dynamic. Coupled with a tumultuous economic environment, this enforces the importance of an expert to assist individuals and businesses in planning for the future. The primary purpose of the Financial Advisory and Intermediaries Services Act (FAIS Act) is to: 1. protect the client against indecorous conduct by the financial service provider (FSP) and its representatives when providing financial advice and/or rendering intermediary services to clients; 2. ensure economic efficiency of the industry; 3. ensure that clients of FSPs are provided with sufficient information regarding their financial products, the representatives selling the products, the represented FSP and the product provider offering the products. The effect of the FAIS Act is that key individuals and representatives are now being held responsible for their actions, which may include providing incorrect information or not having sufficient qualifications or experience. According to the FSB the FAIS Fit and Proper requirements determine a set of requirements that all FSPs, key individuals and representatives need to comply with. The Determination of Fit and Proper Requirements of 2008 outlines the categories of fit and proper requirements for FSPs, their key individuals and representatives. The categories of the FAIS Fit and Proper requirements are: - honesty and integrity requirements for FSPs, key individuals and representatives; - competency requirements of FSPs, key individuals and representatives; - experience requirements of FSPs, key individuals and representatives; - qualifications requirements of key individuals and representatives; - regulatory examinations requirements of key individuals and representatives; - continuous professional development requirements of FSPs, key individuals and representatives; - operational ability of FSPs, key individuals and representatives; and - solvency of FSPs. The empirical study of the research was conducted nationally, within South Africa. The focus of the study was to investigate the perception of financial planners with regard to the regulatory and legislative prescriptions of the financial-services industry. The general objective of the study is to provide a quantitative measure of the perception of financial planners of the effect that the legislative and regulatory requirements in South Africa have on the ethicality of the financial-planning industry. To achieve this objective, the empirical study focussed on the responsibilities of financial-services providers and the FAIS fit and proper requirements as set out by the FAIS Act. The population identified for the empirical study consisted of financial planners that provide advisory and/or intermediary services in South Africa. The population of the study consisted of the full advisory complement, 826, which form part of the advisory division of a major South African financial-services provider. These financial planners are located across South Africa, in all nine provinces and in rural and metropolitan areas. Based on the result of the adjusted sample size equation, the required sample size for the study is reduced from 266 to 201. A total of 260 responses were received for the study which ensures a high level of accuracy is achieved from the findings of the research. The results of the empirical study provide ample proof that financial planners support the necessity and specificity of the FAIS fit and proper requirements as defined by the FAIS Act. Additionally, the financial planners agree that the determinants of the FAIS Act are not only beneficial to the sustainability and ethicality of the industry, but also support the success of the planner and ultimately ensure that clients receive the best possible financial advisory and/or intermediary services. / MBA, North-West University, Potchefstroom Campus, 2015

In dieser Arbeit wurde die alte Designvariante des Fabry-Pérot-Filters (FPI4) hinsichtlich Performance und Ausbeute untersucht. Zielstellung war eine Optimierung, welche die Probleme wie Sticking, Kurzschluss zwischen Schirm und Elektrode sowie Defekte bei den Vereinzelungsverfahren beseitigen sollten. Ferner wurden eine Chipbezeichnung und eine neue geteilte Elektrode anvisiert. Ergebnis dieser Optimierung war das neue Design FPI5. Weiterhin wurde neben der Auslegung des FPI5 für das adhäsive Bonden mit SU8 eine Designvariante für das direkte Bonden realisiert. Das direkte Bonden konnte bereits bei den FPI mit zwei beweglichen Reflektorträgern erfolgreich getestet werden und soll nun auf die Designvariante mit nur einem beweglichen Reflektorträger übertragen werden. Außerdem wurde eine Überprüfung der SU8-Bondfestigkeit durchgeführt. Dabei konnte nachgewiesen werden, dass die bis dato benutzten Bondparameter nicht das Optimum bezüglich der Bondfestigkeit darstellen, da in Testverbunden mit veränderten Bondparametern bis zu 50 % höhere Bondfestigkeiten erreicht wurden. / This work presents a new design type of the older well known tunable micromachined Fabry-Pérot filter (FPI4). Compared to the previous system the new design (FPI5) aimed to avoid the problems as sticking, short circuit between the shield and the electrode as well as the malfunction in dicing and separation. Furthermore an identification mark and a new separated electrode were to be improved. The conclusion of this optimization was the new Design FPI5. The whole geometry was in addition to the adhesive bonding with SU8 moreover designed for the direct bonding, which was successfully verified in the FPI design with two moveable reflector carriers. Additionally a verification of the bonding strength at different bonding parameters was done. This verification showed that a 50 % higher bonding strength could be achieved by using the new bonding parameters in comparison to the normally used bonding parameters.

Summaries in English, Afrikaans and Zulu / This study explored the determinants of foreign portfolio investment (FPI) in emerging markets, using panel data analysis. In all three models, main data analysis using the dynamic generalized methods of moments (GMM) approach showed that FPI was positively and significantly by its own lag. This result confirms the view in the literature (Barrell and Pain. 1999; Wheeler and Mody. 1992; Saini. 2000), which argues that existing foreign investors attract other foreign investors as a result of the positive spillovers that they generate. Financial development also had a positive and a significant effect on FPI in all the three models under the fixed effects, random effects and the fully modified ordinary least squares (FMOLS). Moreover, a significant positive relationship running from financial development towards FPI was also detected in model 1 under the pooled OLS method. The findings resonate with those of Bartels et al. (2009), whose study observed that financial markets improve international mobility of capital through their ability to make use of timely, cheaper and efficient to prospective foreign investors. Model 2 produced results that showed that the impact of financial development on FPI was significantly negative under the pooled OLS approach, in line with Gordon and Gupta’s (2004) findings. Trade openness positively affected FPI in a significant manner under the FMOLS, random and fixed effects in all the three models. Similar results were observed in model 1 and 3 under the pooled OLS approach. These results agree with Dobbs et al (2013) that openness to trade addresses any obstacles that might hinder the movement of international capital from one country to another. The complementarity between openness to trade and financial development had a significant negative impact on FPI in all the three models under the random effects, fixed effects and FMOLS. This result is similar to Al-Smadi’s (2018) finding that foreign investors can easily sell off their investments if financial markets are developed and liquid, especially in the presence of high levels of trade openness that facilitates the movement of capital across country borders (Dobbs et al. 2013). In contrast, model 2 under the pooled OLS showed that the combination between financial development and trade openness had a positive significant effect on FPI. This finding agrees with literature which notes that both trade openness and financial development separately and individually enhance FPI. The expectation therefore is that the combination of trade openness and financial development in a particular single country leads to greater FPI inflows. In model 1, the FMOLS, random and fixed effects showed that exchange rates had a significant positive impact on FPI, something that was found in all three models under the pooled OLS approach. This finding supports Haider et al.’s (2016) argument. Models 1, 2 and 3 showed a significant positive relationship running from economic growth to FPI under the fixed effects, FMOLS and pooled OLS econometric estimation techniques. Similar results were observed in models 1 and 2 under the random effects approach. The finding echoes Al-Smadi’s (2018) argument on the relationship between economic growth and FPI. In contrast, the dynamic GMM method showed that economic growth had a negative significant impact on FPI, supporting Leong and Wickramanayake’s (2004) argument that in the presence of high levels of economic growth, local investors prefer to buy back domestic securities from foreign investors, triggering a deleterious effect of FPI inflows. In model 1, the impact of savings on FPI was found to be significantly negative under the fixed effects, random effects, pooled OLS and FMOLS approaches. Similar results were found in model 2 under the random effects and the pooled OLS. These findings contradict the available literature (Masood and Mohsin. 2002; Abdelhafidh. 2013; Ferreira and Laux. 2009) but are similar to those of Al-Smadi (2018), who argues that higher levels of inflation wipe out the value of not only return on capital but also of the original capital invested. Inflation had a significant negative effect on FPI in models 1 and 2 under the pooled OLS approach. Human capital development had a significant positive influence on FPI in models 1 and 2 under the pooled OLS and the dynamic GMM approaches. This result supports Dunning’s (1988) argument that locational advantages exert a significant influence on foreign direct investment or any form of foreign investment. Human capital development was found to be a locational advantage for foreign investment in this case, as Tsaurai (2017a) found. / In hierdie studie is die bepalers van buitelandse portefeuljebelegging (BPB) in ontluikende markte aan die hand van ʼn paneeldataontleding verken. In al drie die modelle het ʼn hoofdataontleding volgens die benadering van dinamiese, veralgemeende metodes van momente (VMM) aangetoon dat sy eie vertraging BPB positief en opmerklik beïnvloed. Hierdie uitslag onderskryf die bevindings in die literatuuroorsig (Barrell & Pain 1999; Wheeler & Mody 1992; Saini 2000). Hiervolgens word aangevoer dat bestaande buitelandse beleggers ander buitelandse beleggers deur hulle positiewe surplusse aanlok. Ook finansiële ontwikkeling het in al drie die modelle onder die benadering van vaste en ewekansige effekte en volgewysigde gewone kleinste kwadrate (VGGKK) ʼn positiewe en opmerklike effek op BPB gehad. Daarby is ʼn opmerklik positiewe verband, wat van finansiële ontwikkeling tot BPB strek, onder die saamgevoegde gewone kleinstekwadrate- oftewel GKK-metode in model 1 bespeur. Hierdie bevinding staaf dié van Bartels et al (2009) dat finansiële markte die internasionale mobiliteit van kapitaal verbeter deurdat hulle tydig goedkoper en doeltreffende inligting aan voornemende buitelandse beleggers verstrek. Die uitslag van model 2, dat die uitwerking van finansiële ontwikkeling op BPB onder die saamgevoegde GKK-benadering opmerklik negatief is, strook met die bevindings van Gordon en Gupta (2004). Oop handel het BPB onder die VGGKK, ewekansige en vaste effekte in al drie die modelle op ʼn opmerklike wyse positief geaffekteer. Soortgelyke uitslae is in model 1 en 3 onder die saamgevoegde GKK-benadering waargeneem. Hierdie uitslae stem ooreen met dié van Dobbs et al (2013), naamlik dat oop handel baie hindernisse uit weg ruim wat die beweging van internasionale kapitaal van een land na ʼn ander belemmer. Die komplementariteit tussen oop handel en finansiële ontwikkeling het ʼn opmerklik negatiewe uitwerking op BPB in al die modelle onder die benadering van ewekansige effekte, vaste effekte en VGGKK gehad. Hierdie uitslag klop met Al-Smadi (2018) se bevinding dat buitelandse beleggers hulle beleggings maklik van die hand kan sit as finansiële markte ontwikkeld en likied is, en in die besonder as handel in hoë mate oop is en kapitaal met gemak oor landsgrense heen kan beweeg (Dobbs et al 2013). In teenstelling hiermee het model 2 onder die saamgevoegde GKK getoon dat die kombinasie van finansiële ontwikkeling en oop handel ʼn opmerklik positiewe effek op BPB het. Hierdie bevinding stem ooreen met dié in die literatuur dat oop handel en finansiële ontwikkeling gesamentlik en afsonderlik BPB aanwakker. Dienooreenkomstig word verwag dat oop handel en finansiële ontwikkeling groter BPB na in ʼn land sal laat vloei. Die VGGKK en ewekansige en vaste effekte het in model 1 getoon dat wisselkoerse ʼn opmerklik positiewe uitwerking op BPB gehad het. Dit het trouens in al drie die modelle onder die saamgevoegde GKK-benadering voorgekom. Hierdie bevinding beaam Haider et al (2016) se argument. Model 1, 2 en 3 het ʼn opmerklik positiewe verband, wat van ekonomiese groei tot BPB strek, onder die vaste effekte, VGGKK en saamgevoegde GKK ekonometriese ramingstegnieke aangedui. Soortgelyke uitslae is in model 1 en 2 onder die benadering van ewekansige effekte waargeneem. Hierdie bevinding sluit aan by Al Smadi (2018) se argument oor die verband tussen ekonomiese groei en BPB. Hierteenoor het die dinamiese GMM-metode getoon dat ekonomiese groei ʼn negatiewe, opmerklike uitwerking op BPB gehad het. Dit staaf Leong en Wickramanayake (2004) se argument dat plaaslike beleggers verkies om binnelandse sekuriteite by buitelandse beleggers terug te koop as ʼn hoë mate van ekonomiese groei aanwesig is, en dat dit ʼn nadelige effek op die invloei van BPB het. In model 1 was die uitwerking van spaargeld op BPB opmerklik negatief onder die benadering van vaste effekte, ewekansige effekte, saamgevoegde GKK en VGGKK. Soortgelyke resultate het in model 2 voorgekom onder die ewekansige effekte en die saamgevoegde GKK. Ofskoon hierdie bevindings strydig met dié in die beskikbare literatuur is (Masood & Mohsin 2002; Abdelhafidh 2013; Ferreira & Laux 2009), strook dit met dié van Al-Smadi (2018) wat beweer dat hoë inflasie nie alleen die opbrengs op kapitaal nie, maar ook die oorspronklike kapitaal uitwis. Inflasie het ʼn opmerklik negatiewe effek op BPB in model 1 en 2 onder die saamgevoegde GKK- en dinamiese VMMbenadering gehad. Die ontwikkeling van menslike kapitaal het ʼn beduidend positiewe invloed op BPB gehad in model 1 en 2 onder die saamgevoegde VKK- en die dinamiese VMM-benadering. Hierdie uitslag beaam Dunning (1988) se argument dat landsgebonde voordele ʼn beduidende invloed op direkte buitelandse belegging of enige ander vorm van buitelandse belegging uitoefen. Tsaurai (2017a) het bevind dat die ontwikkeling van menslike kapitaal in hierdie geval ʼn landsgebonde voordeel vir buitelandse belegging inhou. / Lolu cwaningo luye lwaphenya izizathu zokutshalwa kwezimali emazweni angaphandle, phecelezi (foreign portfolio investment (FPI) ezimakethe ezisafufusayo, ngokusebenzisa uhlelo lokuhlaziywa kwedatha, phecelezii-panel data analysis. Kuwo onke amamodeli omathathu, kuhlelo lokuhlaziywa kwedatha esemqoka, ngokusebenzisa izindlela eziguquguqukayo zezikhathi ezahlukene (GMM) , lokhu kuye kwakhombisa ukuthi i-FPI yathola umthelela omuhle futhi okungumthelela wayo wokushiywa yisikhathi. Lo mphumela uqinisekisa ulwazi olutholakele olumayelana nokubuyekezwa kombhalo wobuciko (Barrell & Pain 1999; Wheeler & Mody 1992; Saini 2000), okuwumbhalo okhuluma ngokuthi abatshalizimali bangaphandle abakhona baheha abanye abatshalizimali bangaphandle okuyinto edalwa yizinzuzo ezinhle ezingumphumela wokutshalwa kwezimali. Ukuthuthukiswa kwezinhlelo zezimali nakho kube nomthelela omuhle nobalulekile kwi-FPI, kuwo wonke amamodeli amathathu, angaphansi kwesimo semiphumela enqunyelwe isikhathi, angaphansi kwemiphumela yazo zonke izinhlelo eziguqulwe ngokugcwele phecelezi fully modified ordinary least squares (FMOLS) . Ngaphezu kwalokho, ubudlelwano obuhle obusemqoka, obuqala ekuthuthukisweni kwezinhlelo zezimali ukuya kuhlelo lwe-FPI, nabo lobudlelwano buye babonakala kumodeli 1, ngaphansi kohlelo lwe pooled OLS method. Ulwazi olutholakele lufana nalolo lukaBartels et al. (2009), lapho ucwaningo lwakhe lwathola ukuthi izimakethe zezimali zithuthukisa ukuthunyelwa kwezimali emhlabeni ngekhono lokusebenzisa ulwazi lwalo ngesikhathi, ngentengo ephansi futhi ulwazi olufanele, lolu lwazi luthunyelwa kubatshalizimali bangaphandle abathembisayo. Imodeli 2 ikhiqize iveze imiphumela ethi umthelela wokuthuthukiswa kwezinhlelo zezimali ohlelweni lweFPI luye lwabonakala lulubi kakhulu ngaphansi kohlelo lwepooled OLS approach, lokhu kuhambisana nolwazi olutholwe nguGordon kanye noGupta (2004). Uhlelo lwezokuhwebelana oluvulekile luye lwaba nomthelela omuhle ohlelweni lweFPI, ngendlela esemqoka kakhulu, ngaphansi kohlelo lweFMOLS, ngaphansi kohlelo lwemiphumela enqunyelwe isikhathi nohlelo olunganqunyelwanga isikhathi, kuwo wonke amamodeli amathathu. Imiphumela efana naleyo yatholakala kumodeli 1 neye 3, ngaphansi kohlelo lwepooled OLS approach. Le miphumela ihambisana naleyo kaDobbs et al. (2013), yona ngile elandelayo; uhlelo oluvulekile lokuhwebelana luyisisombululo sanoma yiziphi izihibe ezingaphazamisa ukuthunyelwa kwezimali emhlabeni ukusuka kwelinye izwe ukuya kwelinye. Ukusebenzisana phakathi kohlelo lokuhweba oluvulekile kanye nohlelo lwezokuthuthukiswa kwezinhlelo zezimali kuye kwaba nomthelela ongemuhle kwiFPI, kuwo wonke amamodeli omathathu, ngaphansi kwemiphumela enganqunyelwanga isikhathi, imiphumela enqunyelwe isikhathi kanye nakwihlelo lweFMOLS. Lo mphumela ufana nalowo ka-Al-Smadi’s (2018) othi abatshalizimali bangaphandle bangatshala kalula izimali zabo uma izimakethe zezimali zithuthukile futhi zinemali elingene, ikakhulukazi uma kukhona amazing aphezulu wohlelo oluvulekile lokuhwebelana, okungamazinga ahola uhlelo lwezokuthunyelwa kwezimali ngaphesheya kwemingcele yamazwe (Dobbs et al. 2013). Okuphikisana nalokhu, imodeli 2, ngaphansi kohlelo lwepooled OLS, luye lwakhombisa ukuthi ukuhlanganiswa kohlelo lwezokuthuthukiswa kwezinhlelo zezimali kanye nohlelo oluvulekile lwezokuhwebelana kuye kwaba nomthelela omuhle kakhulu kwiFPI. Lolu lwazi olutholakele luvumelana nombhalo wobuciko, wona oshoyo ukuthi zombili lezi zinhlelo uhlelo oluvulekile kwezohwebo kanye nokuthuthukiswa kwezinhlelo zezimali, ezehlukene kanye nalezo ezizimele ngayinye, ziqinisa uhlelo lweFPI. Ngalokho, okulindelwe, ukuthi umbimbi oluxuba uhlelo oluvulekile lwezokuhwebelana kanye nezinhlelo zokuthuthukiswa kwezimali, ngandlelathize,, ezweni elilodwa, ziholela izinga eliphezulu lokungena kweFPI. Kumodeli 1, uhlelo lweFMOLS, imiphumela enganqunyelwe naleyo enqunyelwe isikhathi iye yabonisa ukuthi amazinga okushintshelana ngezimali abe nmothelela omuhle kakhulu kwiFPI; okuyinto etholakele kuwo wonke amamodeli omathathu angaphansi kohlelo lwe pooled OLS. Lolu lwazi olutholakele luxhasa umbono kaHaider et al’s (2016. Amamodeli Models 1, 2 kanye neye 3 ziye zakhombisa ubudlelwano obuhle kakhulu obuqala ekuthuthukisweni kwezomnotho ngokohlelo lwe FPI, ngaphansi kwesimo semiphumela enqunyelwe isikhathi, ngaphansi kohlelo lwe FMOLS kanye nasohlelweni lwe pooled OLS okuyindlela esetshenziswa ukulinganisa izinga lokuhluma komnotho. Imiphumela efana nayo le iye yatholakala kumodeli 1 kanye nakumodeli 2, ngaphansi kwemiphumela enganqunyelwe sikhathi. Ulwazi olutholakele luveza imibono ka-Al-Smadi (2018) mayelana nobudlelwano obuphakathi kokuhluma komnotho kanye nohlelo lwe FPI. Okuphikisana nalokho, indlela eguquguqukayo iGMM iye yakhombisa ukuthi ukuhluma komnotho kuye kwaba nomthelela omubi kakhulu kwi FPI, uxhasa umbono ka Leong kanye no Wickramanayake (2004) othi, uma kunamazinga aphakeme okukhula komnotho, abatshalizimali basekhaya bathanda ukuthenga amasheya amabhizinisi asekhaya kubatshalizimali bangaphandle, lokho kuba nomthelela omubi kakhulu ekungeneni kwe FPI. Kumodelil 1, umthintela wokongiwa kwezimali ohlelweni lwe FPI watholakala ukuthi ube nomthelela omubi kakhulu, ngaphansi kwesimo semiphumela enqunyelwe isikhathi, kwemiphumela enganqunyelwanga isikhathi, ohlelweni lwe pooled OLS kanye nasezinhlelweni ze FMOLS. Imiphumela efana nayo le iye yatholakala kumodeli 2, ngaphansi kwemiphumela enganqunyelwe kanye naleyo enqunyelwe isikhathi kanye nasohlelweni lwe pooled OLS. Lolu lwazi olutholakele luphikisana nolwazi lombhalo wobuciko okhona (Masood & Mohsin 2002; Abdelhafidh 2013; Ferreira & Laux 2009), kanti futhi le miphumela ifana naleyo ka-Al-Smadi (2018), yena oshoyo ukuthi amazinga aphezulu amandla emali akaqedi kuphela inzuzo yokutshalwa kwezimali, kodwa aqeda nemali yokuqala etshaliwe. Amandla email aye aba nomthelela omubi kakhulu kwi FPI, kumodeli 1 kanye nnakumodeli 2, ngaphansi kohlelo lwe pooled OLS. Ukuthuthukiswa kwamagugu ayikhono nezingqondo zabasebenzi aye aba nomthelela omuhle ohlelweni lwe FPI, kumamodeli 1 kanye nakumodeli 2, ngaphansi mkohlelo lwe pooled OLS kanye nezindlela eziguquguqukayo ze GMM. Lo mphumela uxhasa umbono kaDunning (1988) othi izinzuzo zendawo ziba nomthelela omuhle kakhulu ohlelweni oluqondile lwezokutshalwa kwezimali emazweni angaphandle noma ngiluphi uhlelo lwezokutshalwa kwezimali emazweni angaphandle. Ukuthuthukiswa kwamagugu angamakhono kanye nemibono yabasebenzi kuye kwatholakala kuyinzuzo yendawo ekutshalweni kwezimali emazweni angaphandle kulesi simo, njengoba lokhu kuye kwatholakala kuTsaurai (2017a). / Business Management / M. Com. (Management Studies)

Cette thèse propose une modélisation aussi générique que possible de la combustion dans les moteurs automobiles dans un cadre de simulation aux grandes échelles. Une première étude aborde la fermeture du terme de transport non résolu pour la flamme de prémélange. Par la suite, un couplage entre les modèles ecfm-les et pcm-fpi est proposé et validé pour intégrer les effets de chimie complexe à la simulation de la flamme de prémélange. Ce travail est étendu par l'adjonction de modélisations spécifiques à l'allumage par bougie et de l'auto-inflammation, toujours en intégrant les effets de chimie détaillée. Des calculs d'application aux combustions anormales dans les moteurs à allumage commandé concluent ce travail. / This work proposes a modeling as generic as possible of the combustion in automotive engines in the framework of large-eddy simulation. A first study addresses the closure of the non resolved transport term for the premixed flame. Then, a coupling between the models pcm-fpi and ecfm-les is proposed and validated to account for the detailed chemistry effects in the premixed flame modeling. This work is extended adding specific models for spark-ignition and auto-ignition, still integrating detailed chemistry effects. This work is ended by computations of abnormal combustions occurring in spark-ignition engines.

Thailand has been one of significant recipients of foreign direct investment (FDI) among developing countries over the last 30 years, and has recorded rapid and sustained growth rates in a number of different industrial categories. Thailand has shown a clear policy transition for foreign investment over time from an import-substitution regime to an export-oriented regime. Before the 1997 Asian Financial Crisis (1985-1996), Thailand had the fastest growing level of exports in manufactured goods among Asian economies. FDI plays a significant role in the Thai economy. Thailand has been pursuing different foreign investment policies at different times depending on the development objectives and economic situation in the country. The main objective of this research is to evaluate the determinants of FDI and foreign portfolio investment (FPI) in Thailand using the extended Gravity Model. Panel data is used to estimate and evaluate the empirical results based on the data for the years 1980 to 2004. It also examines the FDI flows between different locations and their geographical distances in Thailand. The primary research question addresses what factors motivate, attract, and sustain the FDI and FPI in Thailand. In addition, this study also examines the effects of the 1997 Asian Financial Crisis on the inflows of FDI and FPI into Thailand. The results show that the inflows of FDI in Thailand, which are supply-driven, are significantly influenced by its 21 largest investing partners. The 1997 Asian Financial Crisis has no impact on the determinants of the inflows of FDI into Thailand, but positively influences the inflows of FPI into Thailand. Our results also show that increases in GDP and trade between investing partners and Thailand potentially attract more FDI and FPI into Thailand. Investing partners closer to Thailand draw more portfolio investment into Thailand than distant partners – emphasising that distance has a negative impact on the portfolio investment but a negligible impact on the FDI.

Intracellular bacteria have developed various mechanisms to enter and persist in host cells and, at the same time, to evade the host immune response. One such pathogen is Francisella tularensis, the etiological agent of tularemia. After phagocytosis, this Gram-negative bacterium quickly escapes from the phagocytic compartment and replicates in the host cell cytosol. For this mode of infection, several components of the Francisella pathogenicity island (FPI) are critical. Interestingly, some FPI proteins share homology to components of Type VI Secretion Systems (T6SSs), but their assembly and functionality remains to be shown in Francisella.The thesis focused on the characterization of several of these FPI components; more specifically, how they contribute to the infection cycle as well as their possible role in the putative T6SS. We identified three unique mutants, ΔiglG, ΔiglI and ΔpdpE, which to various degrees were able to escape the phagosomal compartment, replicate in the host cytosol and cause host cell cytotoxicity. In contrast, ΔiglE as well as mutants within the conserved core components of T6SSs, VgrG and DotU, were defective for all of these processes. In the case of IglE, which is a lipoprotein and localized to the outer membrane of the bacterial cell wall, residues within its N-terminus were identified to be important for IglE function. Consistent with a suggested role as a trimeric membrane puncturing device, VgrG was found to form multimers. DotU stabilized the inner membrane protein IcmF, in agreement with its function as a core T6SS component. The functionality of the secretion system was shown by the translocation of several FPI proteins into the cytosol of infected macrophages, among them IglE, IglC and VgrG, of which IglE was the most prominently secreted protein. At the same time, the secretion was dependent on the core components VgrG, DotU but also on IglG. Although we and others have shown the importance of FPI proteins for the escape of F. tularensis, it has been difficult to assess their role in the subsequent replication, since mutants that fail to escape never reach the growth-permissive cytosol. For this reason, selected FPI mutants were microinjected into the cytosol of different cell types and their growth compared to their replication upon normal uptake. Our data suggest that not only the metabolic adaptation to the cytosolic compartment is important for the replication of intracytosolic bacteria, but also the mechanism of their uptake as well as the permissiveness of the cytosolic compartment per se.

Pharmacometrics is widely used in drug development. Models are developed to describe pharmacological measurements with data gathered from a clinical trial. The information can then be applied to, for instance, safely establish dose-response relationships of a substance. Glycated hemoglobin (HbA1c) is a common biomarker used by models within antihyperglycemic drug development, as it reflects the average plasma glucose level over the previous 8-12 weeks. There are five different nonlinear mixed-effects models that describes HbA1c-formation. They use different biomarkers such as mean plasma glucose (MPG), fasting plasma glucose (FPG), fasting plasma insulin (FPI) or a combination of those. The aim of this study was to compare their performances on a population and an individual level using model averaging (MA) and to explore if reduced trial durations and different treatment could affect the outcome. Multiple weighting methods were applied to the MA workflow, such as the Akaike information criterion (AIC), cross-validation (CV) and a bootstrap model averaging method. Results show that in general, models that use MPG to describe HbA1c-formation on a population level could potentially outperform models using other biomarkers, however, models have shown similar performance on individual level. Further studies on the relationship between biomarkers and model performances must be conducted, since it could potentially lay the ground for better individual HbA1c-predictions. It can then be applied in antihyperglycemic drug development and to possibly reduce sample sizes in a clinical trial. With this project, we have illustrated how to perform MA on the aforementioned models, using different biomarkers as well as the difference between model weights on a population and individual level.

In dieser Arbeit wurde die alte Designvariante des Fabry-Pérot-Filters (FPI4) hinsichtlich Performance und Ausbeute untersucht. Zielstellung war eine Optimierung, welche die Probleme wie Sticking, Kurzschluss zwischen Schirm und Elektrode sowie Defekte bei den Vereinzelungsverfahren beseitigen sollten. Ferner wurden eine Chipbezeichnung und eine neue geteilte Elektrode anvisiert. Ergebnis dieser Optimierung war das neue Design FPI5. Weiterhin wurde neben der Auslegung des FPI5 für das adhäsive Bonden mit SU8 eine Designvariante für das direkte Bonden realisiert. Das direkte Bonden konnte bereits bei den FPI mit zwei beweglichen Reflektorträgern erfolgreich getestet werden und soll nun auf die Designvariante mit nur einem beweglichen Reflektorträger übertragen werden. Außerdem wurde eine Überprüfung der SU8-Bondfestigkeit durchgeführt. Dabei konnte nachgewiesen werden, dass die bis dato benutzten Bondparameter nicht das Optimum bezüglich der Bondfestigkeit darstellen, da in Testverbunden mit veränderten Bondparametern bis zu 50 % höhere Bondfestigkeiten erreicht wurden.:ABKÜRZUNGS- UND FORMELVERZEICHNIS VI 1 EINLEITUNG 8 1.1 Motivation 8 1.2 Kapitelübersicht 11 2 DAS FABRY-PEROT-INTERFEROMETER 12 3 DAS ALTE DESIGN FPI4 15 3.1 FPI4 15 3.2 Optimierungspunkte und Schwachstellen 17 4 DAS NEUE DESIGN FPI5 19 4.1 Verhindern von Sticking 20 4.2 Isolator zwischen Schirm und Elektrode 22 4.3 Abdichtfolie für den Sägeprozess 22 4.4 Chipbezeichnung 23 4.5 Elektrodenform 23 4.6 Zusammenfassung des Redesigns 25 5 PROZESSTECHNISCHE REALISIERUNG 27 5.1 FPI5 – Direktbond 27 5.1.1 Oberteil 28 5.1.2 Unterteil 30 5.2 FPI5 – SU8 31 5.2.1 Oberteil 32 5.2.2 Unterteil 34 5.3 Selektive Schichtabscheidung der optischen Schichten 36 6 CHARAKTERISIERUNG DER MUSTER 37 6.1 FPI5 – Direktbond 37 6.1.1 Oberteil 38 6.1.2 Unterteil 40 6.1.3 Beschichtung der optischen Schichten in Jena 42 6.1.4 Zusammenfassung 44 6.2 FPI5 – SU8 47 6.2.1 Oberteil 48 6.2.2 Unterteil 49 6.2.3 Beschichtung der optischen Schichten in Jena 52 6.2.4 Zusammenfassung 54 7 BONDEN DER FPI 57 7.1 Vorversuche zur SU8-Bondfestigkeit 57 7.1.1 Realisierung der Bondmuster 59 7.1.2 Charakterisierung der Bondmuster 60 7.1.3 Vereinzelungstests der Bondmuster 63 7.1.4 Bondfestigkeitsüberprüfung der Bondmuster mit abgerundeten Bondrahmen 64 7.1.5 Bondfestigkeitsüberprüfung der Bondmuster ohne abgerundeten Bondrahmen 67 7.2 Direktbonden der FPI 73 7.2.1 Ablauf des Direktbondens 73 7.2.2 Charaktersierung der Bondmuster 76 7.3 SU8-Bonden der FPI 78 7.3.1 Präparation der SU8-Rahmenstruktur 78 7.3.2 Ablauf des SU8-Bondens 80 7.3.2 Charakterisierung der Bondmuster 81 8 ZUSAMMENFASSUNG UND AUSBLICK 83 LITERATURVERZEICHNIS 85 ABBILDUNGSVERZEICHNIS 87 TABELLENVERZEICHNIS 88 ANLAGENVERZEICHNIS 90 / This work presents a new design type of the older well known tunable micromachined Fabry-Pérot filter (FPI4). Compared to the previous system the new design (FPI5) aimed to avoid the problems as sticking, short circuit between the shield and the electrode as well as the malfunction in dicing and separation. Furthermore an identification mark and a new separated electrode were to be improved. The conclusion of this optimization was the new Design FPI5. The whole geometry was in addition to the adhesive bonding with SU8 moreover designed for the direct bonding, which was successfully verified in the FPI design with two moveable reflector carriers. Additionally a verification of the bonding strength at different bonding parameters was done. This verification showed that a 50 % higher bonding strength could be achieved by using the new bonding parameters in comparison to the normally used bonding parameters.:ABKÜRZUNGS- UND FORMELVERZEICHNIS VI 1 EINLEITUNG 8 1.1 Motivation 8 1.2 Kapitelübersicht 11 2 DAS FABRY-PEROT-INTERFEROMETER 12 3 DAS ALTE DESIGN FPI4 15 3.1 FPI4 15 3.2 Optimierungspunkte und Schwachstellen 17 4 DAS NEUE DESIGN FPI5 19 4.1 Verhindern von Sticking 20 4.2 Isolator zwischen Schirm und Elektrode 22 4.3 Abdichtfolie für den Sägeprozess 22 4.4 Chipbezeichnung 23 4.5 Elektrodenform 23 4.6 Zusammenfassung des Redesigns 25 5 PROZESSTECHNISCHE REALISIERUNG 27 5.1 FPI5 – Direktbond 27 5.1.1 Oberteil 28 5.1.2 Unterteil 30 5.2 FPI5 – SU8 31 5.2.1 Oberteil 32 5.2.2 Unterteil 34 5.3 Selektive Schichtabscheidung der optischen Schichten 36 6 CHARAKTERISIERUNG DER MUSTER 37 6.1 FPI5 – Direktbond 37 6.1.1 Oberteil 38 6.1.2 Unterteil 40 6.1.3 Beschichtung der optischen Schichten in Jena 42 6.1.4 Zusammenfassung 44 6.2 FPI5 – SU8 47 6.2.1 Oberteil 48 6.2.2 Unterteil 49 6.2.3 Beschichtung der optischen Schichten in Jena 52 6.2.4 Zusammenfassung 54 7 BONDEN DER FPI 57 7.1 Vorversuche zur SU8-Bondfestigkeit 57 7.1.1 Realisierung der Bondmuster 59 7.1.2 Charakterisierung der Bondmuster 60 7.1.3 Vereinzelungstests der Bondmuster 63 7.1.4 Bondfestigkeitsüberprüfung der Bondmuster mit abgerundeten Bondrahmen 64 7.1.5 Bondfestigkeitsüberprüfung der Bondmuster ohne abgerundeten Bondrahmen 67 7.2 Direktbonden der FPI 73 7.2.1 Ablauf des Direktbondens 73 7.2.2 Charaktersierung der Bondmuster 76 7.3 SU8-Bonden der FPI 78 7.3.1 Präparation der SU8-Rahmenstruktur 78 7.3.2 Ablauf des SU8-Bondens 80 7.3.2 Charakterisierung der Bondmuster 81 8 ZUSAMMENFASSUNG UND AUSBLICK 83 LITERATURVERZEICHNIS 85 ABBILDUNGSVERZEICHNIS 87 TABELLENVERZEICHNIS 88 ANLAGENVERZEICHNIS 90