The three-dimensional structure of a protein molecule is the key to understanding its biological and physiological properties. A major problem in bioinformatics is to efficiently determine the three-dimensional structures of query proteins. Protein NMR structure de- termination is one of the main experimental methods and is comprised of: (i) protein sample production and isotope labelling, (ii) collecting NMR spectra, and (iii) analysis of the spectra to produce the protein structure. In protein NMR, the three-dimensional struc- ture is determined by exploiting a set of distance restraints between spatially proximate atoms. Currently, no practical automated protein NMR method exists that is without human intervention. We first propose a complete automated protein NMR pipeline, which can efficiently be used to determine the structures of moderate sized proteins. Second, we propose a novel and efficient semidefinite programming-based (SDP) protein structure determination method. The proposed automated protein NMR pipeline consists of three modules: (i) an automated peak picking method, called PICKY, (ii) a backbone chemical shift assign- ment method, called IPASS, and (iii) a protein structure determination method, called FALCON-NMR. When tested on four real protein data sets, this pipeline can produce structures with reasonable accuracies, starting from NMR spectra. This general method can be applied to other macromolecule structure determination methods. For example, a promising application is RNA NMR-assisted secondary structure determination. In the second part of this thesis, due to the shortcomings of FALCON-NMR, we propose a novel SDP-based protein structure determination method from NMR data, called SPROS. Most of the existing prominent protein NMR structure determination methods are based on molecular dynamics coupled with a simulated annealing schedule. In these methods, an objective function representing the error between observed and given distance restraints is minimized; these objective functions are highly non-convex and difficult to optimize. Euclidean distance geometry methods based on SDP provide a natural formulation for realizing a three-dimensional structure from a set of given distance constraints. However, the complexity of the SDP solvers increases cubically with the input matrix size, i.e., the number of atoms in the protein, and the number of constraints. In fact, the complexity of SDP solvers is a major obstacle in their applicability to the protein NMR problem. To overcome these limitations, the SPROS method models the protein molecule as a set of intersecting two- and three-dimensional cliques. We adapt and extend a technique called semidefinite facial reduction for the SDP matrix size reduction, which makes the SDP problem size approximately one quarter of the original problem. The reduced problem is solved nearly one hundred times faster and is more robust against numerical problems. Reasonably accurate results were obtained when SPROS was applied to a set of 20 real protein data sets.

The disproportionate burden of disease in the Aboriginal population in Canada has become so great that it is now being referred to as a health ‘crisis’. Evidence suggests that the answer to these ills lies not in the western biomedical model of heath care, but within the Aboriginal traditions of self-determination and holism (RCAP, 1996; O’Neil, Lemckuk-Favel, Allard & Postl, 1999; Romanow, 2002; CIHI, 2004; Maar, 2004; First Nations & Inuit Regional Health Survey, 2004). To this end, First Nations communities have been negotiating with the federal government and transferring responsibility for their community-based health services since 1986, despite the limitations of the federal Health Transfer Policy (Gregory, Russell, Hurd, Tyance & Sloan, 1992; Lavoie, et al, 2005; RCAP, Vol 3, Chp 3, 1996; Speck, 1989). These self-determination initiatives in health attempt to improve the health status of community members. Thus, determining an approach to health service delivery that contributes to positive health outcomes is of particular significance. Examining Island Lake’s evolving model of health service delivery indicates the success of the intergovernmental, interdepartmental, and intersectoral partnership approach they have taken; as evidenced by the Regional Renal Health Program, with dialysis treatment services, that has been established, perhaps for the first time in the country, in a remote First Nations community without existing hospital services. There remains work to be done in creating a holistic system of health service delivery that reflects their unique worldview within a context of health promotion and self-determination; however, their accomplishments to date, established processes, willingness to put their dreams into action and build what has not been built before demonstrate a potential to improve community health and well-being.

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国立情報学研究所で電子化したコンテンツを使用している。

Thesis (M.A.)--University of Hawaii at Manoa, 1993 / Pacific Islands Studies

Lignin is a major chemical component of plants and the second most abundant natural polymer after cellulose. The concerns and interests of agriculture and industry have stimulated the study of genes governing lignin content in plants in an effort to adapt plants to human purposes. Arabidopsis thaliana provides a convenient model for the study of the genes governing lignin content because of its short growth cycle, small plant size, and small completely sequenced genome. In order to identify the genes controlling lignin content in Arabidopsis accessions using Quantitative Trait Locus (QTL) analysis, a rapid micro-scale method of lignin determination is required. The acetyl bromide method has been modified to enable the rapid micro-scale determination of lignin content in Arabidopsis. Modifications included the use of a micro-ball mill, adoption of a modified rapid method of extraction, use of an ice-bath to stabilize solutions and reduction in solution volumes. The modified method was shown to be accurate and precise with values in agreement with those determined by the conventional method. The extinction coefficient for Arabidopsis lignin, dissolved using acetyl bromide, was determined to be 23.35 g-iLcm-1. This value is independent of the Arabidopsis accession, environmental growth conditions and is insensitive to syringyl/guaiacyl ratio. The modified acetyl bromide method was shown to be well correlated with the 72% sulfuric acid method once the latter had been corrected for protein contamination and acid-soluble lignin content (R² = 0.988, P < 0.0001). As determined by the newly developed acetyl bromide method and confirmed by the sulfuric acid method, lignin content in Arabidopsis was found to be a divergent property. Lignin content in Arabidopsis was found to be weekly correlated with growth rate among Arabidopsis accessions (R² = 0.48, P = 0.011). Lignin content was also found to be correlated with plant height among Arabidopsis accessions (R² = 0.491, P < 0.0001).

The world�s indigenous peoples have been subjected to exploitation, discrimination, dispossession, relocation, assimilation and in some cases genocide since contact with the Western world. They have been the victims of an invasion which has since secured their position among the lowest social qualifiers. For centuries, they have been ignored by nation-states throughout the world. However, a new dawn has risen for the first peoples of the world, and for the past two decades thaey have experienced a cultural, political and social revival which has been gaining in popularity, intensity and effectiveness since it�s inception. The politicisation of indigenous movements and their fundamentally local characteristics has occurred at the same time that the world is experiencing a sense of accelerated globalisation. Economic integration through trade agreements has diminished boundaries and has allowed multinational corporations to travel, sell and trade at will. The sense that the world is �one place� has fast become a reality through "the increasing volume and rapidity of the flows of money, goods, people, information, technology and images." (Featherstone, 1995:81) The simultaneous globalisation and localisation of the world seems to be two contradictory phenomenon acting in opposition to one another. However, as several theorists have pointed out, the two are actually related and each to some degree attributes to the existence of the other (Eriksen, 1993:9; Featherstone, 1990:10; Friedman, 1990:327). In fact, indigenous movements themselves, while asserting local issues and rights, have undergone a recent transformation and now attempt to achieve their goals through global strategies. They have expanded their methods and now not only at the community and national levels, but also within the international arena. The Maori and the Native Hawaiians are two groups of indigenous peoples who have been fighting for their rights and land for over a century. Both groups represent small percentages of their nation-states� population. This has forced them to pursue their struggle with creative strategies and persistent, patient pressure. Thus, their struggles have undergone continouos transformations in attempts to discover the most effective formula which would eventually cause their respective nation-states to recognise and address their grievances. Recently, the Maori and the Native Hawaiians, have broadened their movement to incorporate an international tier. Activity on the international level includes international conferences, international visits/exchanges, ratification of indigenous declarations, indigenous networking, and international indigenous solidarity organisations. These activities have increased over the past twenty years as the effectiveness of such activity has also increased. New Zealand, the United States and other nation-states are being held more accountable for past injustices and are being driven to answer to the world�s indigenous community.

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To date, the majority of studies into sex determination and sexual development have focused on the mammalian system due to the mouse model being an excellent tool for developmental biology as well as obvious implications to human health and development. However, the focus on the mammalian system has caused a large fraction of other vertebrate groups to be overlooked. The last decade has seen an array of studies into various non-mammalian organisms like fishes, birds, reptiles, and amphibians. These studies have unveiled a remarkably conserved molecular background utilized for sexual differentiation amongst all vertebrates, ranging from the alligator which employs temperature dependent sex determination to the mouse, which employs genotypic sex determination In this project, I implemented molecular methods traditionally used to study model organisms, to investigate an amphibian species, the cane toad (Bufo marinus). The cane toad was chosen due to its invasive status in Australia, as well as being a representative of one of the most successful and specious families of vertebrates, Bufonidae. Since, its introduction, this species has rapidly spread across the continent, adversely effecting native species throughout its introduced range. Recent studies have identified the disruption of the sex-determination pathway as a realistic goal in an otherwise, seemingly futile, effort to curtail their expansion. We decided to approach the study of cane toad sex determination and development on three levels, in order to have a broader understanding of the similarities between toads and other groups, and additionally, to better assess the feasibility of utilizing molecular means to control cane toads in non-native habitats. Firstly, I used a candidate gene approach to clone and characterize five genes which were previously known to be involved in both mammalian as well as amphibian sex determination: Sox9, Dmrt1, p450arom, Sf1, and Dax1. I chose Sox9 and Dmrt1 due to their known involvement in the male-specific pathway of mammals. Dmrt1 was also known to be male specific in other groups, including amphibians. Conversely, I also decided to investigate p450arom and Dax1, due to their affiliation with the female pathway, while Sf1 has a role in both sexes. All of these genes were expressed in the gonads of both sexes of cane toads. However, Sox9 exhibited strong transcriptional up-regulation in testes at the time of sexual differentiation, similar to mammals. Thus, using the candidate gene approach, I was successful in identifying a sex-specific marker which could be utilized in the manipulation of the sex determination pathway (e.g. female to male sex reversal). VIIThe second approach involved the study of sex determination on a cytogenetic level. Traditionally, Bufonids have been assumed to utilize a ZZ/ZW (male homogametic/female heterogametic) sex chromosome system, yet only one recent study has been successful in the identification of sex chromosomes in a toad species. Moreover, the authors identified the sex chromosomes in only one population (of 18 studied), highlighting the scarcity of discernible sex chromosomes in toads. When we began to investigate the karyotype of cane toads, we were able to identify a female-specific length polymorphism in the nucleolus organizer region (NOR) of chromosome 7, making this chromosome pair a strong candidates for the Z and W sex chromosomes. In order to verify our hypothesis, we also performed chromomycin A3 staining to reveal a differential signal between the chromosome pair, indicative of heterochromatin accumulation on the brighter NOR. This study lent strong support to the observed difference between the chromosomes, yet we required further investigation in order to identify the W and the Z chromosomes, specifically. By utilizing comparative genomic hybridization (CGH), I was able to identify a female specific region on the chromosome with the larger NOR, identifying it as the W chromosome. This study was successful in identifying the sex chromosomes in the cane toad. Moreover, it allows us to make a more accurate prediction of the possible sex determination method utilized: either a dosage dependent male determination system, or a female-specific gene in a female determination system. The third approach focused on the Bidder’s organ and its role in sexual development of cane toads. The Bidder’s organ is a gonadal structure comprised of ovary-like tissue, found in both males and females, with no known function. Since our study was focused on female to male sex-reversal of cane toads, we decided to investigate the potential of the Bidder’s organ to interrupt this process. By utilizing the candidate genes, which I had previously cloned, I was able to identify the Bidder’s organ as having an entirely distinct transcriptional pattern in comparison to the gonads of either sex. Additionally, the Bidder’s organ showed significantly higher levels of p450arom expression than the gonads, identifying it as a possible key player in the production of aromatase enzyme for oestrogen production. Moreover, gene expression patterns in the Bidder’s organ strongly correlated with the significant developmental time points in the sexual development of the toads, implying a possible function in the development process of toads. In conclusion, I have performed the first study of the molecular, cytogenetic and anatomical aspects of sexual development in a toad. I was able to verify that cane toads utilize a ZZ/ZW chromosome system and furthermore, likely utilize the mammalian male-linked gene, Sox9, in male development. I was also able to show that the Bidder’s organ is transcriptionally active at key time points, likely indicative of a functional role during development.

One of the most challenging tasks for augmented reality systems is that of position and attitude determination in outdoor unprepared environments. Augmented reality, a technology that overlays digital information with views of the real world, requires accurate and precise position and attitude determination to operate effectively. For small (often indoor) areas, careful preparation of the environment can allow for augmented reality systems to work successfully. In large outdoor environments, however, such preparation is often impractical, time-consuming and costly. This thesis aims to investigate the development of a position and attitude determination component for augmented reality systems capable of operation in outdoor unprepared environments. The hypothesis tested in this investigation is that the integration of Global Positioning System (GPS), Dead Reckoning (DR) and map matching techniques enables the continuous and accurate real-time visual alignment of three-dimensional data with objects in the perspective view of a user operating in outdoor unprepared environments.