Investment-linked insurance in Taiwan has been listed for almost a decade since 2001. In 2002, after the big sales of the investment-linked insurance, the domestic insurance companies also joined the market. For the investment-linked insurance, the policyholders retain the protection of the life insurance as well as share the earnings of the investment. Since the main investment instruments of the investment-linked insurance are mutual funds, it is important to study how to optimally allocate the portfolio. This research consider the returns of the mutual funds under tree models assumption. The objective is to find the optimal portfolio which has minimum variance and attained a given expected return level. The problem is also known as mean-variance portfolio problem. In the empirical work, we study eleven daily mutual fund price data from Sep. 2007 to Nov. 2008. Using the data of the first 12 months, we first establish initial tree price models, then update the parameters of the tree model by the EWMAmethod. The optimal trading strategies of the mean-variance portfolio are investigated under this model setting. We class the mutual funds into three categories: equity funds, balanced funds and bond funds. Different combination of these three kinds of funds are considered to find the optimal trading strategy respectively. The results showed that the realized returns using this optimal trading strategy in practice is close to the pre-specified expected return level.

This paper examines the impact of credit rating migration in determining optimal capital structure. The models we propose capture empirical behavior in two ways; the behavior of linking firm¡¦s rating to the promised coupons and the behavior of targeting minimum rating. We find that as long as the rating at issuing time is not too low, tax shields of the rating-linked coupon debt are larger than those of standard debt with the same par, and hence, optimal leverage usage of the firm with the rating- linked coupon scheme is greater. Further, we also show that the behavior of targeting a minimum rating causes mean-reverting leverage dynamics. Managers are appeared to make over-repurchase choices for adjusting the current rating back to the initial target following a downgrade from target minimum rating.

<p>The long-term external financing of a corporation is satisfied through the bond market where issues of index-linked bonds, which are discussed in this thesis, is one alternative. (Finnerty&Emery 2001) An index- linked bond is a debt instrument where the investor is guaranteed the principal and premium amount in real terms. As the bonds cash flows are indexed to the inflation this implies that the issuer of an index-linked bond assumes an inflation risk. Purpose: The purpose of this thesis is to describe and examine corporate motives for choosing index-linked bonds as way of financing their business. Realization: Primary data was collected through interviews with corporate issuers of non-swapped index-linked bonds. Results: From our research it has been acknowledged that both internal and external factors determine the decision to issue index-linked bonds. The most important internal reason for the issuance was that this type of financing implies matching advantages, which helps lowering the companies’ risks. This is achieved by balancing the size and time of the cash inflows with the cash out- flows. Of the external factors we found that it is primary the financing cost that is of interest. The cost savings are primarily achieved because of the lower liquidity premium demanded when using index-linked bonds as a way of financing the business. We believe that this depends partly on the character of the investors and on market imperfections.</p>

The nuclear matrix (NM) is proposed to be a permanent network of core filaments underlying thicker fibres, present regardless of transcriptional activity. It is found to be both RNA and protein rich; indeed, numerous important nuclear proteins are components of the structure. In addition to mediating the organisation of entire chromosomes, the NM has also been demonstrated to tether telomeres via their TTAGGG repeats. In order to examine telomeric interactions with the NM, a technique known as the DNA halo preparation has been employed. Regions of DNA that are tightly attached to the structure are found within a so-called residual nucleus, while those sequences forming lesser associations produce a halo of DNA. Coupled with various FISH methodologies, this technique allowed the anchorage of genomic regions by the NM, to be analysed. In normal fibroblasts, the majority of chromosomes and telomeres were extensively anchored to the NM. Such interactions did not vary significantly in proliferating and senescent nuclei. However, a decrease in NM-associated telomeres was detected in quiescence. Since lamin A is an integral component of the NM, it seemed pertinent to examine chromosome and telomere NM-anchorage in Hutchinson-Gilford Progeria Syndrome (HGPS) fibroblasts, which contain mutant forms of lamin A. Indeed, genome tethering by the NM was perturbed in HGPS. In immortalised HGPS fibroblasts, this disrupted anchorage appeared to be rescued; the implications of this finding will be discussed. This study also suggested that telomere-NM interactions are aberrant in X-linked Emery-Dreifuss Muscular Dystrophy (X-EDMD), which is caused by mutant forms of emerin, another NM-associated protein. The positioning of selected genes in control and X-EDMD cell lines was examined in un-extracted nuclei using 2D and 3D FISH. Subtle shifts in the organisation of these genes were detected in diseased cells; however, their expression levels remained unaltered. Furthermore, in order to examine the architectural integrity of the nuclear lamina in lamin A and emerin mutant cell lines, scanning electron microscopy (SEM) was employed. This work revealed that such structures were indeed compromised in disease. The findings presented in this thesis highlight the importance of lamin A and emerin in mediating the organisation of the genome and taken together, promote the hypothesis that dysfunctional NM dynamics may well contribute to disease pathology.

Intellectual disability is a prevalent developmental disorder for which no effective treatments are available. Mutations of the X-linked protein PHF6 cause the Börjeson-Forssman-Lehmann syndrome (BFLS) that is characterized by intellectual disability and epilepsy. However, the biological role of PHF6 relevant to BFLS pathogenesis has remained unknown. Here, I present my dissertation research demonstrating that knockdown of PHF6 profoundly impairs neuronal migration in the mouse cerebral cortex in vivo, leading to the formation of white matter heterotopias that harbor aberrant patterns of neuronal activity. Importantly, BFLS patient specific mutation of PHF6 blocks its ability to promote neuronal migration. I also elucidate the mechanism by which PHF6 drives neuronal migration in the cerebral cortex. PHF6 physically associates with the PAF1 transcription elongation complex, and inhibition of PAF1 phenocopies the PHF6 knockdown-induced migration phenotype in vivo. I further identify Neuroglycan C (NGC), a susceptibility gene for schizophrenia, as a critical downstream target of PHF6 and the PAF1 complex, and I demonstrate that NGC mediates PHF6-dependent neuronal migration. These findings define PHF6, the PAF1 transcription elongation complex, and NGC as components of a novel cell-intrinsic transcriptional pathway that orchestrates neuronal migration in the brain, with important implications for the pathogenesis of intellectual disability and potentially other neuropsychiatric disorders.

Ο αυξητικός παράγοντας πλειοτροπίνη (Pleiotrophin, PTN) έχει μοριακή μάζα 18 kDa και ανήκει σε μια διακριτή οικογένεια αυξητικών παραγόντων που δεσμεύονται στην ηπαρίνη και σχετίζονται με αγγειογένεση και καρκινική ανάπτυξη. Στην παρούσα εργασία, μελετήσαμε τη συμμετοχή των ενδοκυτταρικών κινασών FAK και ILK στην επαγόμενη από PTN κυτταρική μετανάστευση σε ανθρώπινα ενδοθηλιακά κύτταρα από φλέβα ομφάλιου λώρου (HUVEC). Εξωγενής χορήγηση ΡΤΝ επάγει τη φωσφορυλίωση της κινάσης FAK στις τυροσίνες 397 και 925, ενώ μειώνει τη φωσφορυλίωση της κινάσης FAK στη τυροσίνη 576. Η κινάση ILK φαίνεται να εμπλέκεται στη διεγερτική δράση της PTN στη μετανάστευση των κυττάρων HUVEC, αφού μείωση της έκφρασης της κινάσης ILK με παρεμβαλλόμενο RNA στα κύτταρα HUVEC, οδήγησε σε αναστολή της επαγόμενης από ΡΤΝ κυτταρικής μετανάστευσης. Επιπλέον, διέγερση των κυττάρων HUVEC με PTN είχε ως αποτέλεσμα την επαγωγή της ενεργοποίησης της κινάσης ILK. Με σκοπό να διερευνηθεί η θέση της κινάσης ILK στο μονοπάτι μεταγωγής σήματος που ενεργοποιείται από τη PTN στα κύτταρα HUVEC, μελετήσαμε την πιθανή αλληλεπίδραση της ILK με μόρια που είναι γνωστό ότι συμμετέχουν σε αυτό το μονοπάτι. Παρατηρήθηκε ότι η κινάση ILK αλληλεπιδρά σε μεγάλο βαθμό με την κινάση FAK, ενώ μικρού βαθμού αλληλεπίδραση φαίνεται και με τις ιντεγκρίνη β3 και κινάση c-Src. Ενδιαφέρον παρουσιάζει το γεγονός ότι η διέγερση με PTN των κυττάρων HUVEC αυξάνει την αλληλεπίδραση μεταξύ των κινασών FAK και ILK. Τέλος, με δεδομένο ότι η β-κατενίνης εμπλέκεται στη κυτταρική μετανάστευση, ερευνήσαμε κατά πόσο η PTN και η κινάση ILK εμπλέκονται στο σηματοδοτικό μονοπάτι της β-κατενίνης στα κύτταρα HUVEC. Η ΡΤΝ αυξάνει με δοσο-εξαρτώμενο και χρονο-εξαρτώμενο τρόπο τη φωσφορυλίωση της β-κατενίνης σε κύτταρα HUVEC, φαινόμενο που αναστέλλεται μετά τη μείωση της έκφρασης της κινάσης ILK με siRNA. Συμπερασματικά, στην παρούσα εργασία καταδεικνύεται ότι η ΡΤΝ έχει διαφορική δράση στη φωσφορυλίωση τυροσινών της κινάσης FAK διαφορετικών θέσεων και ότι η κινάση ILK συμμετέχει στη διεγερτική δράση της PTN στη μετανάστευση των κυττάρων. / Pleiotrophin (PTN) is an 18 kDa secreted growth factor that displays high affinity for heparin. A growing body of evidence indicates that PTN is involved in cell proliferation, migration and differentiation. In the present work, we studied the possible role of two intracellular kinases, focal adhesion kinase (FAK) and integrin-linked kinase (ILK), in the PTN-induced migration of human umbilical vein endothelial cells (HUVEC). Exogenous administration of PTN significantly increased the phosphorylation of FAK kinase in tyrosines 397 and 925 and decreased phosphorylation in tyrosine 576. ILK seems to be involved in PTN-induced migration of HUVEC, since suppression of the ILK kinase using small interfering RNA (siRNA) abolished the stimulatory effect of PTN in migration of HUVEC. In addition, stimulation of HUVEC with PTN increased the ILK kinase activity. In order to determine which other signaling mediators are involved in the PTN signaling pathway, we studied the interaction of ILK with other proteins that have been implicated in the PTN-induced signal transduction. ILK strongly interacted with FAK kinase and to a lesser extent with c-src kinase and integrin ανβ3. Interestingly, PTN increased the degree of interaction between ILK and FAK kinases. Finally, it has been well described that β-catenin is involved in cell migration and that PTN increases β-catenin phosphorylation. We therefore investigated whether PTN affects β-catenin phosphorylation in HUVEC through activation of ILK kinase. PTN significantly increased phosphorylation of β-catenin in a concentration and time dependent manner, which seemed to be abolished after suppression of the ILK kinase using siRNA. Collectively, these results suggest a role of FAK and ILK kinases in the PTN-related signaling cascade which leads to cell migration both human endothelial cells.

Structured products are investment vehicles that combine basic financial instruments to provide private investors with packaged solutions to more advanced investment strategies in financial markets. This paper investigates the pricing of 22 index-linked notes examined during their full life cycles between January 12, 2005 and January 17, 2007. The selected products constitute some 40% of the structured products issued by Swedbank in 2005, which at the time of the study is the second largest issuer of structured products to private investors in Sweden. Quoted prices on secondary markets are compared with duplication strategies using exchange traded options in order to calculate price differences. The pricing results show that quoted prices deviate very little from their theoretical values in secondary markets. The price deviations are surprisingly low in an international comparison. Some indications have been found that the market maker is able to influence prices on secondary market by orienting the pricing towards the relative life cycle and moneyness of the structured products. The importance of patterns in price deviations can, however, be questioned since the absolute level of pricing errors is low. There is little evidence to suspect that the issuer, Swedbank, systematically quotes prices that are not in line with their theoretical values. Sophisticated investors are thus likely to be able to judge the attractiveness of the structured product issue by comparing the transaction costs of the instruments in a duplication strategy with the transaction costs of the structured product. The author welcomes further research that includes multiple issuers to determine whether these findings apply for the Swedish market as a whole.

Increased reactive oxygen species (ROS) have been reported to be at the centre of various diseases. Although several reports have implicated elevated levels of ROS in the pathogenesis of diabetes mellitus, the early detection of ROS is still not attainable. This limitation causes difficulty in the early diagnosis of ROS related disorders. The presence of high levels of ROS was reported to result in differential expression of antioxidant genes involved in protecting cells from their deleterious effects. Among the antioxidant genes that are expressed, it was postulated that expression of metallothioneins (MTs) are also induced. MTs are low molecular weight, cysteine-rich proteins involved in metal homeostasis and reported to harbour antioxidant function. The aim of this investigation was to explore MTs as biomarkers for elevated levels of ROS in whole blood of type 2 diabetic (T2D) individuals. The level of ROS in diabetic, non-diabetic as well as individuals at risk of developing T2D was determined via the use of biochemical assays. Real-Time PCR was utilised to analyse the expression of MTs and the presence of MT proteins was analysed via the ELISA. In this study it was observed that diabetic individuals had elevated levels of ROS. However, no significant difference in the expression of MTs and the presence of MT proteins between the diabetic and non-diabetic individuals was observed. In vitro experimental conditions indicated that MT expression is induced by elevated levels of ROS. In pathological conditions the ROS-dependent induction of MT expression needs to be elucidated further. It therefore can be suggested that MTs can not yet be utilised as biomarkers for the detection of elevated levels of ROS in pathological conditions with ROS aetiology. This investigation also highlights the fact that blood is not an optimal medium in which this objective can be attained. / Thesis (Ph.D. (Biochemistry))--North-West University, Potchefstroom Campus, 2005.

As individuals are increasingly benefiting from the use of online services, there are growing concerns about the treatment of personal information. Society’s ongoing response to these concerns often gives rise to privacy policies expressed in legislation and regulation. These policies are written in natural language (or legalese) as privacy agreements that users must agree to, or presented as a set of privacy settings and options that users must opt in or out of in order to receive the service they want. But comprehensibility of privacy policies and settings is becoming increasingly challenging as agreements become longer and there are many privacy options to choose from. Additionally, organizations face the challenge of assuring compliance with policies that govern collecting, using, and sharing of personal data. This thesis proposes frameworks for personalized privacy and privacy auditing to address these two problems. In this thesis, we focus our investigation on the comprehensibility issues of personalized privacy using the concrete application domain of personal health data as recorded in systems known as personal health records (PHR). We develop the Privacy Goals and Settings Mediator (PGSM) model, which is based on i* multi-agent modelling techniques, as a way to help users comprehend privacy settings when employing multiple services over a web platform. Additionally, the PGSM model helps privacy experts contribute their privacy knowledge to the users’ privacy decision-making task. To address the privacy auditing problem, we propose two light-weight ontologies, L2TAP and SCIP, that are designed for deployment as Linked Data, an emerging standard for representing and publishing web data. L2TAP (Linked Data Log to Transparency, Accountability and Privacy) provides flexible and extensible provenance-enabled logging of privacy events. SCIP (Simple Contextual Integrity Privacy) provides a simple target for mapping the key concepts of Contextual Integrity and enables SPARQL query-based solutions for two important privacy processes: compliance checking and obligation derivation. This thesis validates the premise of PHR users’ privacy concerns, attitudes and behaviour through an empirical study. The usefulness of the PGSM model for privacy experts is evaluated through interviews with experts. Finally, the scalability and practical benefits of L2TAP+SCIP for log-based privacy auditing are validated experimentally.

As individuals are increasingly benefiting from the use of online services, there are growing concerns about the treatment of personal information. Society’s ongoing response to these concerns often gives rise to privacy policies expressed in legislation and regulation. These policies are written in natural language (or legalese) as privacy agreements that users must agree to, or presented as a set of privacy settings and options that users must opt in or out of in order to receive the service they want. But comprehensibility of privacy policies and settings is becoming increasingly challenging as agreements become longer and there are many privacy options to choose from. Additionally, organizations face the challenge of assuring compliance with policies that govern collecting, using, and sharing of personal data. This thesis proposes frameworks for personalized privacy and privacy auditing to address these two problems. In this thesis, we focus our investigation on the comprehensibility issues of personalized privacy using the concrete application domain of personal health data as recorded in systems known as personal health records (PHR). We develop the Privacy Goals and Settings Mediator (PGSM) model, which is based on i* multi-agent modelling techniques, as a way to help users comprehend privacy settings when employing multiple services over a web platform. Additionally, the PGSM model helps privacy experts contribute their privacy knowledge to the users’ privacy decision-making task. To address the privacy auditing problem, we propose two light-weight ontologies, L2TAP and SCIP, that are designed for deployment as Linked Data, an emerging standard for representing and publishing web data. L2TAP (Linked Data Log to Transparency, Accountability and Privacy) provides flexible and extensible provenance-enabled logging of privacy events. SCIP (Simple Contextual Integrity Privacy) provides a simple target for mapping the key concepts of Contextual Integrity and enables SPARQL query-based solutions for two important privacy processes: compliance checking and obligation derivation. This thesis validates the premise of PHR users’ privacy concerns, attitudes and behaviour through an empirical study. The usefulness of the PGSM model for privacy experts is evaluated through interviews with experts. Finally, the scalability and practical benefits of L2TAP+SCIP for log-based privacy auditing are validated experimentally.