Mycobacterium tuberculosis, the principal causative agent of tuberculosis (TB) in humans, is considered to be a successful pathogen owing to the elicitation of multidrug resistance, ability to survive inside macrophage phagosomes by taking nutrients from host cell cytoplasm, and the capacity to alternate between proliferating and dormant (nonproliferating) conditions of growth. Thus, whether one looks at tubercle bacillus from the standpoint of regulation of cell division in the host system, or uptake of nutrients from the host cell cytoplasm or elicitation of drug resistance, the requirement for ATP Binding Cassette (ABC) transporter type protein complexes, which might be involved in the transport of drugs, nutrients or proteins, could be of critical importance to the pathogen. Therefore the present study was initiated to characterize ABC transporter type proteins, FtsE and FtsX of M. tuberculosis (MtFtsE and MtFtsX), and their interaction with FtsZ and FtsQ, which are the septation proteins that are recruited respectively before and after the localization of FtsE and FtsX proteins. The study was carried out in 3 parts. 1. Cloning, overexpression and purification of MtFtsE and MtFtsX proteins and elucidation of ATP binding activity of MtFtsE There exists considerable extent of homology between the FtsE and FtsX proteins of M. tuberculosis and E. coli. Therefore, in order to verify whether the structural homology is reflected in functional homology, complementation of growth defect of E. coli ftsE (Ts) by MtFtsE and MtFtsX was carried out. The MtFtsE protein could partially complement growth defect of E. coli ftsE temperature sensitive strain MFT1181, whereas co-expression of MtFtsE and MtFtsX efficiently complemented growth defect, indicating that the MtFtsE and MtFtsX proteins functionally complement E. coli FtsE and FtsX and that the two proteins together might be performing an associated function. Subsequently, in order to biochemically characterize MtFtsE and MtFtsX proteins of M. tuberculosis, MtftsE gene was cloned in pQE30, overexpressed, purified by Ni2+-NTA agarose affinity chromatography under denaturing conditions and refolded. MtFtsX protein, being toxic to E. coli cells, could not be expressed to sufficient amounts. Western blotting with anti-MtFtsE antibody showed that the recombinant 6xHis-MtFtsE protein and the native MtFtsE protein were localized to the membrane of E. coli and M. tuberculosis cells respectively. 6xHis-MtFtsE protein showed ATP binding in vitro, whereas K42R mutation abolished ATP binding. Thus, like in the case of E. coli FtsE, the K42 residue, which is positionally equivalent to K41 in EcFtsE in Walker A motif, was found to be essential for ATP binding. At 1.3 nM concentration of [α32P] ATP,70 molar excess of ATP, ADP, AMP, and GTP competed out respectively 97%, 87%, 73% and 57% of the [α32P] ATP bound to 6xHis-MtFtsE. 2. Biochemical characterization of MtFtsE protein The functional architecture of an ABC transporter consists of two each of nucleotide binding domain (NBD) and transmembrane domain (TMD), which are either part of a single polypeptide chain or individual subunits. The functional NBD is a ‘nucleotide-sandwich dimer’ with ATP flanked by the Walker A and B motifs of one NBD and the signature motif and D-loop of the other. NBD, through ATPase activity, is involved in energizing the transport of substrates namely drugs, proteins, ions, and solutes across the membrane. Since MtFtsE possesses Walker A and Walker B motifs that constitute NBD, and MtFtsX possesses TMD (four transmembrane segments), the two proteins together might constitute an ABC transporter type complex. Therefore, we wanted to know whether MtFtsE could hydrolyze ATP. MtFtsE not only could bind ATP with high affinity but could hydrolyse it also (Km, 1.5 µM; Vmax, 0.87 nmole/mg/min). It could bind and hydrolyse GTP as well, but not CTP, albeit with lower affinity and rate (Km, 25 µM; Vmax, 0.54 nmole/mg/min). The ATPase activity is strongly dependent on Mg2+ or Mn2+, with a pH optimum of 6.5 – 8.0 and temperature range of 27oC - 40oC. Kinetic analysis of ATPase and GTPase activities indicated nucleotide- dependent cooperativity (Hill coefficient for ATP is 1.7 and for GTP, 2.1). Inhibition of ATPase activity, to almost similar extent, in the presence of 10-fold excess of ATPγS, ADP, AMP, GTP, and CTP, but not TTP, indicated that nucleotide binding is through nitrogenous base of the nucleotide. Inhibition of MtFtsE by orthovanadate classified the enzyme as a P-type ATPase. Partially purified MtFtsE in soluble fraction also showed ATPase activity. The ATPase-active form of MtFtsE is a dimer with the sole cysteine (C84) at the dimer interface. Homology modeling of MtFtsE, using MalK (the NBD component of an ABC transporter for maltose) as the template, supported this observation. Stabilization of the dimer through cys-cys disulphide bond increased ATPase activity by 3.7-fold, although C84 does not have any role in ATPase activity. 3. Identification and elucidation of interaction among cell division proteins FtsE, FtsX, FtsQ and FtsZ of Mycobacterium tuberculosis Septum synthesis in E. coli is mediated by a dozen of proteins, among which the bacterial cytoskeletal protein FtsZ is the first molecule to localise to the mid-cell site, where it forms a scaffold for the localization of downstream cell division proteins namely, FtsA /ZipA < FtsE / FtsX < FtsK < FtsQ < FtsL < FtsB < FtsW < FtsI < FtsN and AmiC. If the above order of recruitment of proteins holds true for M. tuberculosis as well, the immediate proteins recruited to the mid-cell site after MtFtsZ in M. tuberculosis would be MtFtsE and MtFtsX, followed with MtFtsK and MtFtsQ. Thus it is possible that MtFtsE and MtFtsX could be interacting with MtFtsZ and MtFtsQ. Therefore attempts were made to delineate the interaction network among MtFtsE, MtFtsX, MtFtsQ and MtFtsZ of M. tuberculosis. Ni2+-NTA agarose pulldown, co-immunoprecipitation and bacterial two-hybrid assays using wild type and deletion mutants of the proteins showed that MtFtsE interacts with MtFtsQ and MtFtsX through its C-terminus. In addition, MtFtsX could interact with MtFtsZ and MtFtsQ. MtFtsX was found to homodimerise and interact with MtFtsQ in vivo. The ATPase-active of MtFtsE in vivo being a dimer, a hypothetical model for the translocation of MtFtsQ into the membrane at mid-cell site was proposed. According to this model, MtFtsQ might be inserted into the membrane at the mid-cell site by (MtFtsX)2 functioning as the membrane channel for the transport, which could be energized by the ATPase subunit (MtFtsE)2 of the (MtFtsE)2(MtFtsX)2 complex. MtFtsX might have a role in tethering the FtsZ-ring with the membrane at the mid-cell site. An altogether different possibility could be that the (FtsE)2(FtsX)2 complex might have a role in the stabilization or constriction of FtsZ-ring during the inward growth of septum.

The thesis investigates the relationship between corporate social responsibility (CSR) and financial performance. The thesis is organised into three parts. The first part, the literature review, is in three sections, the first section provides an introduction to the field of corporate social responsibility, its grounding in economic theory and its historical background. The second part of the literature review covers the social and environmental issues relevant specifically to the food and agriculture sector. The third section is a systematic review of the studies that examine the relationship between corporate social performance and financial performance. This review was carried out using a modified Cochrane systematic review method, more commonly found in the medical literature than in the economics literature. The results showed that 70% of the studies reviewed showed a positive and statistically significant relationship between CSR and financial performance. The second part of the thesis includes three empirical studies. The first study, an event study, assessed the impact of the FTSE4Good Index on firm price. The study examined the return to companies of being included in a modified share index that signals good performance in terms of CSR. The results of this event study showed that companies are not rewarded for being included in the index and are not penalised for being deleted from it. The second empirical study, a probit analysis, aimed to identify the probability of a company passing a social and environmental screen given information about the company’s size, financial performance and sector. Results showed that companies with small market capitalisation, low income gearing and high net profit margins were more likely to pass the screen than other companies. Companies in the energy sector were less likely to pass than other companies, and financial sector companies more likely to pass. The third empirical chapter assessed the effect on the financial performance of companies of passing a socially responsible investment screen. The results showed that there was a relationship between passing the screen and higher earnings per share, but the relationship between passing the screen and other financial indicators was not proven. These studies demonstrated the difficulties that exist to provide statistically strong evidence for the relationship between corporate social responsibility and financial performance. Thus the third part of the thesis moved into a different area, from the supply to the demand side. This is the valuation of non-financial indicators and their relationship with CSR, this included a discursive chapter on intangibles and their relationship with CSR and a final empirical study: a choice experiment. This study demonstrated that MBA students take nonfinancial and ethical issues into account when making investment decisions. In conclusion, providing strong evidence for the relationship between corporate social responsibility and financial performance is difficult. There are many ways of measuring CSR and many ways of measuring financial performance. Depending on the measures used, different results are obtained. Looking beyond conventional financial performance measurements, to intangibles, provides a more holistic picture of what is going on in the relationship and shows that there is more to company valuation and investment decision making than financial performance indicators. CSR is an important component of company reputation and has an intrinsic value that is difficult to measure but is no doubt very high.

The purpose of this thesis is to investigate the relationship between female representation on boards of British FTSE 100 companies and their corporate performance. The theoretical section sets the foundation for the initial hypotheses that there is a positive relationship between the percentage of women on corporate boards and a firm's profitability, measured as ROE and ROIC. The methodological part establishes an analytical framework to test these hypotheses utilizing the so-called 'quartile approach'. The FTSE 100 companies are categorized into quartiles in accordance with their respective percentage of female directors and subsequently, the average values of ROE and ROIC are calculated for each quartile and compared between each other. The research in the practical part of the thesis shows that profitability varies significantly when comparing the least and most gender diverse FTSE 100 boards. The aim of the thesis was reached by proving the positive correlation between the percentage of female board members and profitability, validated by sensitivity and statistical analyses.

This study attempts to measure the effects on the share price of companies entering and exiting four FTSE/JSE indices; the J200, J210, J213 and J260. While results showed only weak statistical significance, systematic patterns were observed during the event window. Share prices of companies entering and exiting value weighted indices responded consistently with the investor awareness hypothesis. Share prices of companies entering and exiting indices weighted by fundamental factors responded consistently with the information hypothesis. The cumulative average abnormal returns (CAARs) were permanent and did not reverse within the first 200 days after the index change for all indices. Abnormal returns were calculated by using the market model and a one factor CAPM model. The market model was a superior benchmark in this study. This study found that the CAARs for index changes became positive only after the date of the index change. This implies that either the effect of passive index funds on the JSE is not significant, or that passive funds are allowed to incur tracking errors in order to trade strategically to secure the best price for a reconstituted portfolio. This conclusion is supported by the fact that there was no observable change in the index premium over time. The findings of this study may indicate market inefficiency, which means that arbitrage opportunities may exist around index changes. / Dissertation (MBA)--University of Pretoria, 2012. / Gordon Institute of Business Science (GIBS) / unrestricted

No / We examine short- and the long-term price effect associated with the FTSE 100 index revisions. We control for both heteroskedastic nature of the residual and the change, between the estimation and the test period, in the beta coefficient of the standard market model. Our findings reveal no relationship between the long-term price reversals and the change in the discount rate, as approximated by the beta coefficient of the market model. Overall, we provide strong evidence in favour of the price pressure hypothesis, where the price increase (decrease) gradually starting before the announcement an inclusion (exclusion) and reverses completely in less than two weeks after the index revision date.

Prediction of financial time series is described as one of the most challenging tasks of time series prediction, due to its characteristics and dynamic nature. In any investment activity, having an accurate prediction system will significantly benefit investors by guiding decision making, especially in trading, asset management and risk management. Thus, the attempts to build such systems have attracted the attention of practitioners in the market and also researchers for many decades. Furthermore, the purpose of this thesis is to investigate and develop a new approach to predicting financial time series with consideration given to their dynamic nature. In this thesis, the prediction procedures will be carried out in three phases. The first phase proposes a new hybrid dynamic model based on Ensemble Empirical Mode Decomposition (EEMD), Back Propagation Neural Network (BPNN), Recurrent Neural Network (RNN), Support Vector Regression (SVR) and EEMD-Genetic Algorithm (GA)-Weighted Average (WA) to predict stock index closing price. EEMD in this phase is introduced as a preprocessing step to historical observation for the first time in the literature. The experimental results show that the EEMDD-GA-WA model performance is a notch above the other methods utilised in this phase. The second phase proposes a new hybrid static model based on Wavelet Transform (WT), RNN, Support Vector Machine (SVM), Nave Bayes and WT-GA-WA to predict the exact change of the stock index closing price. In this phase, the experimental results showed that the proposed WT-GA-WA model outperformed the rest of the models utilised in this phase. Moreover, the input data that are fed into the hybrid model in this phase are technical indicators. The third phase in this research introduces a new Hybrid Heuristic-Rules-based System (HHRS) for stock price prediction. This phase intends to combine the output of the hybrid models in phase one and two in order to enhance the final prediction results. Thus,to the best of our knowledge, this study is the only one to have carried out and tested this approach with a real data set. The results show that the HHRS outperformed all suggested models over all the data sets. Thus, this indicates that combining di↵erent techniques with diverse types of information could enhance prediction accuracy.

This study examines the role of board social and human capital in assessing the market value of firms in the UK context. As the world economy has shifted from manufacturing to service and knowledge-based economies, attributes such as knowledge, expertise, skills, ability and reputation are increasingly fundamental to the success of business enterprises. There is a growing consensus that these attributes are an increasingly valuable form of capital, asset or resource, despite their intangibility. In accounting, there are a number of problems arising from the accountability of non-physical, non-financial capital. Firstly, some forms of capital and certain assets are neither recognised nor presented in the statement of financial position. Secondly, some accounting practices relating to intangible assets are very conservative, resulting in undervalued assets and overstated liabilities. Consequently, there is an increasing gap between the book value and market value of firms. This gap restricts the relevance of information presented in financial statements and suggests that there is something missing in financial statements. This is the research problem being addressed in this study. While prior literature demonstrates that it has proven difficult to operationalise intangible forms of capital, there has been significant empirical attention and theoretical development in social and human forms. This thesis aims to contribute to accounting theory and practice by exploring the impact that board social and human capital have on firm market value. In light of extant research, it is hypothesised that social and human capital possessed at board level are positively related to the market value of firms. This study employs the Ohlson’s (1995) residual income valuation model to test the impact of social and human capital using a sample of UK firms listed on the FTSE All Share index for a period of 10 years (2001-2010). Social and human capital measures are derived from interlocking directorate ties and detailed biographic information of board directors. This study benefits from Pajek and Ucinet network packages to generate network maps and calculate positional metrics such as centrality and structural hole measures.

This study investigates FTSE/JSE All Share index monthly and daily equity returns for evidence of the January and TY effect. Four different measures of monthly return are analysed for the 1995-2006 period, whilst daily returns are analysed during the 1995-2005 period. In addition to this, analysis is conducted on monthly Fama-MacBeth risk premium estimates tor the FTSE/JSE All Share Index. Descriptive statistics are first analysed, followed by ANOV A or Kruskai-Wallis tests, the paired t-test and finally dummy variable regression analysis in investigating the seasonality of FTSE/JSE All Share Index returns and risk premia. Analysis on monthly returns reveals an absence of the January effect, however a positive slightly statistically significant December effect is found. Thus, investors earn abnormal returns on equity during the month of December. The results from the Fama-MacBeth risk premia estimates reveals highly statistically significant negative risk premia seasonal patterns during March, July and September. Thus, investors are in fact penalised for investing in equities during these months. In addition, the analysis reveals an absence of a December effect in risk premia, which contradicts the risk-return trade-off central to modem finance. The daily return analysis reveals a highly significant Turn-of-the-Year effect (TY), which suggests that investors earn abnormal returns on days at the turn of the year. Therefore, it is concluded that a December effect is apparent in South African equity monthly returns, whilst a March, July and September effect is apparent in South African equity risk premia contradicting the risk-return trade-off central to modem finance. In addition to this, a TY effect is present in South African equity daily returns.

Few studies have examined the impact of portfolio concentration upon the realised volatility of stock index portfolios, such as the FTSE 100. Instead, previous research has focused upon diversification across industries, across geographic regions and across different firms. The present study addresses this imbalance by calculating the daily time series of four concentration metrics for the FTSE 100 Index over the period from January 1984 through March 2003. In addition, the value weighted variance covariance matrix (VCM) of daily FTSE 100 Index constituent returns is decomposed into four sub-components: two from the diagonal elements and two from the off-diagonal elements of the VCM. These consist of the average variance of constituent returns, represented by the sum of diagonal elements in the VCM, and the average covariance represented by the sum of off-diagonal elements in the VCM. The value weighted average variance (VAV) and covariance (VAC) are each subdivided into the equally weighted average variance (EAV) the equally weighted average covariance (EAC) and incremental components that represent the difference between the respective value-weighted and equally weighted averages. These are referred to as the incremental average variance (IAV) and the incremental average covariance (IAC) respectively. The incremental average variance and the incremental average covariance are then combined, additively, to produce the incremental realised variance (IRV) of the FTSE 100 Index. The incremental average covariance and the incremental realised variance are found to be negative during the 1987 crash and the 1992 ERM crisis. They are also negative for a substantial part of the study period, even when concentration was at its highest level. Hence the findings of the study are consistent with the notion that the value weighted, and hence concentrated, FTSE 100 Index portfolio is generally less risky than a hypothetical equally weighted portfolio of FTSE 100 Index constituents. Furthermore, increases in concentration tend to precede decreases in incremental realised volatility and increases in the equally weighted components of the realised VCM. The results have important implications for portfolio managers concerned with the effect of changing portfolio weights upon portfolio volatility. They are also relevant to passive investors concerned about the effects of increased concentration upon their benchmark indices, and to providers of stock market indices.

Η παρούσα διπλωματική ασχολείται με το ζήτημα των διαρθρωτικών μεταβολών στη μη δεσμευμένη διακύμανση χρηματιστηριακών στοιχείων. Παρουσιάζονται διάφοροι έλεγχοι που χρησιμοποιούνται στην εμπειρική έρευνα, μαζί με μια σύντομη παρουσίαση των επιπτώσεων από την αγνόηση της ύπαρξης τέτοιων μεταβολών. Η διπλωματική ολοκληρώνεται με μια εμπειρική εφαρμογή, στις μετοχές που συνθέτουν τον δείκτη FTSE20 του Χρηματιστηρίου Αξιών Αθηνών. Συγκεκριμένα, ο έλεγχος Kokoszka-Leipus εφαρμόζεται στο τετράγωνο των λογαριθμικών αποδόσεων με τη χρήση μιας διαδοχικής διαδικασίας τμηματοποίησης, προκειμένου να διερευνηθεί η ύπαρξη σημείων διαρθρωτικής μεταβολής που συνδέονται με την τρέχουσα οικονομική-χρηματοπιστωτική κρίση. / The present dissertation deals with the subject of structural breaks in the unconditional variance of stock market data. It contains a presentation of various tests that are used in empirical research for detecting structural change, as well as a brief presentation of the consequences when such changes are ignored. The dissertation is concluded with an empirical application on the individual stocks that compose the FTSE20 Index of the Athens Stock Exchange. More specifically, the Kokoszka-Leipus test is being applied to the squared log returns using a sequential segmentation procedure, in order to detect structural breakpoints which are related to the recent economic/financial crisis.