In previous research on pricing mortality-linked securities, the no-arbitrage approach is often used. However, this method, which takes market prices as given, is difficult to implement in today's embryonic market where there are few traded securities. In particular, with limited market price data, identifying a risk neutral measure requires strong assumptions. In this thesis, we approach the pricing problem from a different angle by considering economic methods. We propose pricing approaches in both competitive market and non-competitive market. In the competitive market, we treat the pricing work as a Walrasian tâtonnement process, in which prices are determined through a gradual calibration of supply and demand. Such a pricing framework provides with us a pair of supply and demand curves. From these curves we can tell if there will be any trade between the counterparties, and if there will, at what price the mortality-linked security will be traded. This method does not require the market prices of other mortality-linked securities as input. This can spare us from the problems associated with the lack of market price data. We extend the pricing framework to incorporate population basis risk, which arises when a pension plan relies on standardized instruments to hedge its longevity risk exposure. This extension allows us to obtain the price and trading quantity of mortality-linked securities in the presence of population basis risk. The resulting supply and demand curves help us understand how population basis risk would affect the behaviors of agents. We apply the method to a hypothetical longevity bond, using real mortality data from different populations. Our illustrations show that, interestingly, population basis risk can affect the price of a mortality-linked security in different directions, depending on the properties of the populations involved. We have also examined the impact of transitory mortality jumps on trading in a competitive market. Mortality dynamics are subject to jumps, which are due to events such as the Spanish flu in 1918. Such jumps can have a significant impact on prices of mortality-linked securities, and therefore should be taken into account in modeling. Although several single-population mortality models with jump effects have been developed, they are not adequate for trades in which population basis risk exists. We first develop a two-population mortality model with transitory jump effects, and then we use the proposed mortality model to examine how mortality jumps may affect the supply and demand of mortality-linked securities. Finally, we model the pricing process in a non-competitive market as a bargaining game. Nash's bargaining solution is applied to obtain a unique trading contract. With no requirement of a competitive market, this approach is more appropriate for the current mortality-linked security market. We compare this approach with the other proposed pricing method. It is found that both pricing methods lead to Pareto optimal outcomes.

Biological/biochemistry analyses traditionally require bulky instruments and a great amount of volume of biological/chemical agents, and many procedures have to be performed in certain locations such as medical centers or research institutions. These limitations usually include time delay in testing. The delays may be critical for some aspects such as disease prevention or patient treatment. One solution to this issue is the realization of point-of-care (POC) testings for patients, a domain in public health, meaning that health cares are provided near the sites of patients using well-designed and portable medical devices. Transportation of samples between local and central institutions can therefore be reduced, facilitating early and fast diagnosis. A closely related topic in engineering, lab-on-a-chip (LOC), has been discussed and practiced in recent years. LOC emphasizes integrating several functions of laboratory processes in a small portable device and performing analysis using only a very small amount of sample volume, to achieve low-cost and rapid analysis. From an engineer's point of view, LOC is the strategy to practice the idea of POC testing. This dissertation aimed at exploring the POC potentials of porous membrane-base LOC devices, which can be used to simplify traditional and standard laboratory procedures. In this study, three LOC prototypes are shown and discussed. First the protein sensor incorporating with silica nanofiber membrane, which has shown 32 times more improvement of sensitivity than a conventional technique and a much shorter detection time; secondly the bacteria filter chip that uses a sandwiched aluminum oxide membrane to stabilize the bacteria and monitor the efficacy of antibiotics, which has reduced the test time from 1 day of the traditional methods to 1 hour; the third is the sensor combining microfluidics and silica nanofiber membrane to realize Surface Enhanced Raman Spectroscopy on bio-molecules, which has enhancement factor 10^9 and detection limit down to nanomolar, but simple manufacturing procedures and reduced fabrication cost. These results show the porous-base membrane LOC devices may have potentials in improving and replacing traditional detection methods and eventually be used in POC applications.

Monogenic disorders offer a possibility for studies of genetic disturbances in hearing impairment—a knowledge which could be essential for development of future treatment options. In this thesis, the underlying genetic disturbances in neurofibromatosis 2 (NF2) and familial Meniere’s disease (FMD) were evaluated, and familial X-linked hearing impairment was described from a clinical point of view. In paper I, constitutional DNA from 116 individuals with NF2 of variable severity was studied using the array-CGH method focusing on a 7.6-Mb area surrounding the NF2 gene on chromosome 22q. Deletions were found in 20.7% of samples. In mild NF2, the deletions were small, but variable sizes of deletions were found in cases that were moderately or severely affected. Disease phenotype could not be predicted from the size of the deletions. In papers II and III, a single five-generation family with autosomal dominant FMD was described. Anticipation concerning age of onset was observed. Genome scan revealed five candidate gene regions with a LOD score of > 1. Two additional families with autosomal dominant MD were analyzed for linkage to these five regions. A cumulative Zmax of 3.46 was obtained for a single 463-kb region on chromosome 12p12.3, containing only one known gene: PIK3C2G. This encodes a protein with a proposed role in hair cell regeneration in mammalian ears. No mutations were found in protein-coding sequences or exon-intron borders. In two of the three families, a shared haplotype, suggested common ancestry, was found to extend over 1.7 Mb, which could be a genomic region of importance for FMD. In paper IV, a family in which five males displayed progressive low- and mid-frequency hearing impairment from the first or second decade was described. Female carriers were affected by a high-frequency hearing impairment from the fourth decade. The family could represent a novel X-linked dominant audiophenotype.

Potato leafroll virus (PLRV) causes yield and quality losses in potato. PLRV is identified by plant symptoms and serological tests such as an enzyme-linked immunosorbent assay (ELISA). A similar serological test, direct tissue blotting assay (DTBA), was used to detect and monitor PLRV movement in field-inoculated Russet Burbank plants and plant tissues from Russet Burbank and Russet Norkotah seed tubers submitted by growers for winter certification tests. DTBA was as accurate as ELISA and easier to use for detecting tuber-perpetuated PLRV in stems and petioles of plants grown from grower-submitted seed tubers. ELISA detected twice as many PLRV positives as DTBA in leaflet tests. DTBA detected PLRV in tuber tissue but results matched ELISA in only 74% or less of the samples. Results of DTBA tuber tests were sometimes difficult to interpret while stem and petiole results were distinct and unambiguous. As inoculations were delayed later in the season and as plants matured, PLRV infection levels decreased sharply, most often within a two week period in early July. In same-age plants inoculated 43 days after planting but 18 days apart, early inoculation produced higher PLRV levels. Conversely, when same-age plants were inoculated 62 days after planting but 19 days apart, late inoculation produced higher PLRV levels. This discrepancy is not fully understood, but larger tuber size at the later inoculation probably produced a stronger sink for source-to-sink translocation of nutrients and phloem-limited viruses. Results of DTBA winter grow-out tests of summer-infected tubers approximated those of ELISA and visual inspections. Indirect DTBA testing of tubers utilizing stem and petiole tissues from winter growout plants detected more PLRV than directly testing tuber tissue 21 days post inoculation in summer. DTBA detected current season (primary) PLRV less reliably than secondary (tuber-borne) PLRV, similar to reported ELISA results. PLRV infection increased tuber numbers but decreased size. Size reduction was most evident in plants infected early in the season. Average tuber size in healthy plots was always larger than the average tuber size in infected plots. Within an infected plant, small tubers tended to be infected less often than large tubers. / Graduation date: 1993

The concept of strategic entrepreneurship has received increased attention over the past ten years. Viewed as the intersection of entrepreneurship and strategy, this field of research is populated by conceptual studies which focus mainly on the nature and perceived benefits of strategic entrepreneurship. Similarly, the study of entrepreneurship in a public sector context has gained increasing support in recent years, but also remains underexplored. To address these gaps, this thesis considers: What are the underlying elements and financial implications of strategic entrepreneurship in New Zealand’s state-owned enterprises [SOEs]? New Zealand’s SOE sector, comprising 17 government-owned, commercially focused organisations, is considered to be a prime subject for this research. Well known for their implementation of new public management [NPM], many New Zealand SOEs have also been publicly recognised as both innovative and entrepreneurial. The research question is addressed by first developing a preliminary framework of strategic entrepreneurship from literature on entrepreneurship and strategy. This framework is then examined in the context of case studies on activity which is entrepreneurial and/or strategic within 12 of the 17 SOEs operating in New Zealand as at 2006. Transcripts from a series of interviews, and publicly available documents are analysed thematically. SOEs’ financial statements over a five year period are also analysed. The thesis contributes in two broad areas. First, much-needed empirical support is lent to the concept of strategic entrepreneurship. Key elements of strategic entrepreneurship identified include opportunity identification, innovation, acceptance of risk, flexibility, vision, growth, and leveraging from core skills and resources such that existing knowledge and skills are transferred and applied to create new products, services, and markets. Important supporting elements identified include an open, flexible, and progressive culture, operational excellence, and cost minimisation. The nature of each of these elements is also investigated. A detailed understanding of the relationship between strategic entrepreneurship and wealth creation reveals various internal and external factors which may influence the nature and strength of the relationship. These factors include changes within the organisation, as well as changes in the economic and political environment, and are important influences on the resulting returns realised. Second, this thesis offers valuable evidence in support of emerging change in the public sector towards the adoption of strategic entrepreneurship. Support for the value of NPM is provided, with clear evidence of financial returns from New Zealand’s SOE sector. Further, a key finding is the structured and systematic approach to entrepreneurial activity within the context of NPM in several New Zealand SOEs. Such behaviour is referred to in this thesis as new public entrepreneurship. This form of activity offers the potential for competitive advantage and financial gain traditionally associated with entrepreneurial activity, but also limits the respective risks through its structured, systematic approach.

The dystrophinopathies are a group of disorders characterised by cellular absence of the membrane stabilising protein, dystrophin. Duchenne muscular dystrophy is the most severe disorder clinically. The deficiency of dystrophin, in the muscular dystrophy X-linked (mdx) mouse causes an elevation in intracellular calcium in cardiac myocytes. Potential mechanisms contributing to increased calcium include enhanced influx, sarcoplasmic reticular calcium release and\or reduced sequestration or sarcolemmal efflux. This dissertation examined the potential mechanisms that may contribute to an intracellular calcium overload in a murine model of muscular dystrophy. The general cardiomyopathy of the mdx myocardium was evident, with the left atria from mdx consistently producing less force than control atria. This was associated with delayed relaxation. The role of the L-type calcium channels mediating influx was initially investigated. Dihydropyridines had a lower potency in contracting left atria corresponding to a redued dihydropyridine receptor affinity in radioligand binding studies of mdx ventricular homogenates (P<0.05). This was associated with increased ventricular dihydropyridine receptor protein and mRNA levels (P<0.05). The function of the sarcoplasmic reticulum in terms of release and also sequestration of calcium via the sarco-endoplasmic reticulum ATPase were investigated. A lower force of contraction was evident in mdx left atria in response to a range of stimulation frequencies (P<0.05) and concentrations of extracellular calcium (P<0.05). However, in the presence of 1 nM Ryanodine to block sarcoplasmic reticular calcium release, increased stimulation frequency caused similar forces to those obtained in control mice suggesting enhanced calcium influx via L-type calcium channels in mdx. Rapid cooling contractures showed a reduced contracture in mdx compared to control in response to cooling. This suggests some dysfunction in SR storage, which may be associated with the delayed relaxation time. Concentration-response curves to inhibitors of the sarco-endoplasmic reticulum showed no difference in function of the enzyme responsible for calcium uptake into the sarcoplasmic reticulum. Although sarco-endoplasmic reticulum ATPase mRNA was upregulated, no functional benefit was evident. This study indicates that a deficiency of dystrophin leads to upregulation of L-type calcium channels that contribute to increased calcium influx, with no functional change in sarcoplasmic reticular sequestration. Upregulation of the influx pathway is a potential mechanism for the calcium overload observed in mdx cardiac muscle.

Universiẗat, Diss., 2007--Giessen.

Thesis (Ph.D.). / Written for the Dept. of Biomedical Engineering. Title from title page of PDF (viewed 2008/01/12). Includes bibliographical references.

Thesis (Ph.D.). / Written for the Dept. of Human Genetics. Title from title page of PDF (viewed 2008/02/12). Includes bibliographical references.

Thesis (Ph. D.)--Cornell University, January, 2009. / Vita. Includes bibliographical references (leaves 104-114).