The Dalmatian is affected by deafness more than any other breed of domestic dog, with 30% of the United States population suffering from unilateral or bilateral deafness. The genetic origin of deafness in the Dalmatian is unknown. The objective of this work was to identify, using linkage analysis, any chromosomal region(s) in which the gene(s) responsible for deafness in the Dalmatian may be located. To achieve this objective it was necessary to 1) develop multiplexed microsatellite markers for an efficient whole genome scan, 2) assemble a multigenerational Dalmatian kindred segregating deafness, 3) estimate the heritability of deafness and perform complex segregation analysis, and 4) perform linkage analysis of deafness, and other phenotypic traits, in the Dalmatian kindred. A set of 172 microsatellite markers, termed Minimal Screening Set 1 (MSS1), was characterized, prior to this work, for whole genome scans of the domestic dog. 155 of the MSS1 markers were multiplexed into 48 multiplex sets. Amplification of the multiplex sets was achieved using a single thermal cycling program. The markers were labeled with fluorescent dyes and optimized for resolution on an ABI 310 Genetic Analyzer or ABI 377 Sequencer. A kindred of 266 Dalmatians was assembled, of which 199 had been diagnosed using the brainstem auditory evoked response to determine auditory status. Of these, 74.4% (N = 148) had normal hearing, 18.1% (N = 36) were unilaterally deaf, and 7.5% (N = 15) were bilaterally deaf. A heritability of 0.73 was estimated considering deafness a dichotomous trait and 0.75 as a trichotomous trait. Although deafness in the Dalmatian is clearly heritable, the evidence for the presence of a major gene affecting the disorder was not persuasive. Dalmatians (N = 117) from the assembled kindred were genotyped for the MSS1 markers (149 were polymorphic). Linkage analysis was performed for deafness, eye color, and spot color. The maximum LOD scores for deafness were found with markers Cos15 on CFA17 (LOD = 1.69) and FH2585 on CFA28 (LOD = 1.34). No significant linkage was found with eye color. Significant linkage for spot color was found with marker FH2319 (LOD = 9.7) on CFA11.

The EU’s Trade Relations with China (1975-2008): A Linkage Power at Work? (Summary) The central aim of this thesis is to improve our understanding of the EU’s power, in particular in its external trade relations/negotiations. Our hypothesis is that the EU is a distinctive kind of linkage power, defined as an actor relying on linkage as a crucial modus operandi in its external relations. We explored how, to what extent and in which distinctive ways the EU is such a linkage power. Our analysis was based on three logically interrelated concepts – power resources, linkage and linkage power. Linkage refers to a leveraging strategy, with an aim of packaging relevant power resources, so as to increase leverage in bargaining, or more generally attain a policy objective. I identified seven types of linkages that the EU used: political-economic issue linkage, economic-economic issue linkage, conditionality, contextual linkage, linkage with a third party, cognitive linkage and synergistic linkage. Linkage can hardly work without proper power resources. The latter, as Dahl (1970) defined, refers to all the resources-opportunities, acts, objects etc – that an actor can exploit in order to affect the behaviour of another. So, linkage is a bridge between power resources and impacts – meaning affecting or changing the behaviour of another party. By putting linkage and power together, we created a new term – “linkage power”, referring to a power based on linkages. The EU, the US, China or any other power can all be such labelled, though these actors may diverge in power resources, linkage strategies and the variables affecting linkage effectiveness. When applying such an analytical framework to the EU, we gave particular attention to the implications of the EU’s sui generis nature on its linkage power. Our case study is the EU’s trade relations with China (1975-2008), which were punctuated by two critical historical junctures – the Tian’anmen Square Incident in 1989 and the EU-China Textile Crisis in 2005. In 1975, The EEC’s successful strategy by linking political issues (Europe-China balancing the Soviet Union and recognising China’s sovereignty over Taiwan) with economic issues (signing the EEC-China Trade Agreement) played a crucial role in securing the establishment of diplomatic relations between the EEC and China. Different types of linkages were then applied to the EEC’s negotiations with Beijing on the 1978 Trade Agreement and the 1979 textile agreement, which effectively prompted the Chinese side to agree to the EU’s terms. Immediately after the 1989 Tian’anmen Square Incident, the EC imposed economic sanctions with an aim of coercing China to accept Western world’s human rights conditions. This linkage did not last long or pay off due to divergent political and economic interests among the Member States and the EC’s institutional handicaps (foreign policy competence was largely in the hands of Member States, collective foreign policy action was non-binding), and soon de-linked. Having realised that confrontational approach did not work well, the EC/EU and its Member States started to change their China policies in 1993-95. The period of 1993-2004 witnessed the EC/EU’s power through partnership. The strategic partnership was seen as a complex of different pairs of issue linkages, ranging from political-strategic issues to economic and human rights issues. The partnership, once established, had fostered new linkages and consolidated old ones. China’s WTO accession was seen as a once-in-a-century opportunity for the EU to exercise linkage through conditionality, so as to extract market access concessions from the Chinese side. Moreover, by linking with China could the European Commission garnered international support for advancing the Galileo project within the Union and ward off some of the US pressure in 2003. The Year 2005 was singled out since an unprecedented trade row on textiles broke out, confronting the EU against China’s export prowess resulting from globalisation and China’s WTO accession. Linkages were used as a predominant strategy to help the EU to persuade and press the Chinese side firstly accept voluntary export restrictions and then share the burden of allowing the blocked textiles in European ports to be released. In 2006-08, the trade deficit problem emerged, coupled with a series political spats between Europe (France and Germany) and Beijing on the Tibet issue. As the EU-China honeymoon was over, the Commission toughened its approach towards China. Although linkage was again used to redress the trade deficit, its effects were not satisfactory, as the EU power resources were eroded. Our conclusions are (1) linkage is a crucial modus operandi in the EU’s internal bargain and its external relations with China; (2) Linkage was generally effective vis-à-vis China, but with variations, either over time or across different linkage types; (3) The EU is a sui generis linkage power, resulting from its institutional characteristics and heterogeneity of interests among the Commission and Member States. We find that the EU’s increased institutionalisation (both regional and bilateral) and competences generally facilitated its use of linkage strategies. The EU’s sui generis structure and its internal interest divergences have mixed implications on its linkage effectiveness. On one hand, the EU’s linkage power was weakened accordingly. But on the other, the Commission could tactically make use of some Member State government’s row with Beijing and advance its own economic agenda (such as the EU-China High-level Economic and Trade Dialogue, HED). Moreover, our research also confirmed Andrew Moravcsik’s argument that issue linkage is more easily made within an issue-area than across issue-areas. But we differ from him on the reason behind that. We find that this was largely attributable to the EU’s pillar structure and competence divisions. The theoretical contributions include: (1) Linkage power provides a distinctive prism to look into the EU’s concrete strategies in internal bargains, and external commercial negotiations. Linkage serves as a crucial strategy for the EU to handle its relations with a far-abroad country like China, including establishing diplomatic relations, negotiating trade deals, forging strategic partnerships and holding high-level dialogue. (2) Giving some insights to the EU’s actorness. We find that the EU, though institutionally not a unitary actor, was somehow able to present its power to the extent like a sovereign state on some occasions using linkage strategies. (3) Contributing to the understanding of the EU’s means to spread its governance model. We find that the EU’s norm-setting goals have often been achieved through non-normative ways – such as interest exchange and trade-off, and other deliberate ways of persuasion and even coercion, mainly based on linkage. (4) Shedding light on the interactions between the Commission and the Member State governments and on the Commission’s autonomy in external trade relations. Two future directions of research have been identified: (1) comparative studies: the EU’s linkage practices vis-à-vis the US, Russia and middle powers, or other actors’ linkage strategies vis-à-vis China; (2) post-Lisbon linkage strategies used by the EU.

The domestic dog, Canis familiaris, with over 450 naturally-occurring hereditary diseases, serves as a valuable model organism for study of the genetics underlying many human hereditary diseases. Approximately half of the diseases that afflict the dog are clinically very similar to various human hereditary diseases. Several cardiac diseases are in this category. Our laboratory is interested in cardiac diseases because they are common causes of death in the human and are also a widespread problem in many breeds of dog. The specific focus of my work is on understanding the genetics of dilated cardiomyopathy (DCM). DCM is a disease characterized by enlargement of the left ventricle leading to an inability of the heart to pump sufficient blood to the body. It is one of the most common cardiac diseases in the dog and has a high mortality. The Great Dane is the second most commonly affected breed. It is seen in many families of Great Danes, and this suggests that DCM has a genetic component. The mode of inheritance of DCM in the Great Dane is currently unknown, although studies have reported both autosomal recessive and autosomal dominant transmission. Many different genes cause DCM, indicating the complexity of the disease. These typically produce proteins that are involved in the sarcomere or cytoskeletal components, leading to problems with contraction or cardiac cell integrity. In order to identify causative or susceptibility genes for DCM in the Great Dane, a whole-genome linkage screen was conducted in a family of Great Danes. One candidate gene, gamma-sarcoglycan (SGCG), was identified through linkage and sequenced in affected and unaffected dogs. Sequencing data revealed no mutations in the coding regions of SGCG, most likely excluding it as a candidate gene for DCM. Continued evaluation of this gene and others, both in sequence content and additional properties such as epigenetic effects, protein structure, and interaction with other genes will increase understanding of DCM in both the dog and the human.

Positive natural selection is recognized as the driving force underneath evolution. One of the surest signatures of recent positive selection is a local elevation of advantageous allele frequency and linkage disequilibrium (LD). This dissertation proposes a new test statistic to detect excess homozygosity based on a simple counting measure, which serves as a surrogate indicator of recent positive selection. Three tests are developed upon the new measure: (a) an extended genotype-based homozy- gosity test (EGHT), (b) a hidden Markov model test (HMMT), and (c) an extended haplotype-based homozygosity test (EHHT). The null hypotheses of all three tests assume random mating and Hardy-Weinberg equilibrium (HWE). They differ in how to treat LD under H0 . The EGHT assumes linkage equilibrium (LE) besides HWE while the EHHT allows arbitrary multi-locus LD. The HMMT stands between these two extremes and assumes pairwise but no higher-order disequilibrium interactions. We first conduct simulation study to compare the three score tests and verify that the EHHT is the most conservative one. We compare the performance of the EHHT with the prevailing detection methods and the EHHT has higher or similar power. We also evaluate the impact of simple demographic history on the EHHT and the simulation study suggests that the EHHT is resistant to the false-positive confounders resulting from simple demographic models. After extensive simulation studies, all three tests are then applied on HapMap Phase II data and we are able to replicate findings reported in the literature. We can also identify new candidate regions that may undergo recent selection through a set of filtering criteria including highest EHHT scores, high derived allele frequency and large population differentiation. Finally, we propose a cross-population comparison test statistic to detect chromosome regions in which there is no significant excess homozygosity in one population but homozygosity remains high in another population.

From the viewpoint of land economics, any change in land use manner will require new public facilities added to the area under development and bear external impact on the area. The merit of the fundamental principle to remove, through levying rezoning on land use, the external effects brought on by alterations in development should be recognized. However, because the levy of rezoning on land utilization involves people¡¦s rights and obligations, the proper execution of this system has a considerable impact on people¡¦s privilege. The current rezoning system on land utilization implemented in Taiwan has been in practice for many years; it is also widely criticized. Concerns over such subjects as ambiguous definition and nature of rezoning, lack of legal status for the levy of rezoning, lack of standard for the calculation of rezoning amounts are usually raised. Therefore, the government must work to try to establish a complete, reasonable rezoning system on land utilization. The author conducted the research by examining the system of impact fees and linkage fees implemented in the United States, the planning obligations system implemented in Britain, and the development charge system implemented in Singapore and examining their experience, and reviewing the relevant laws and concerns with regard to the current rezoning on land utilization in Taiwan. Moreover, after analyzing and describing the policy trend of the government¡¦s effort to establish the land development obligations system, the author tried to understand, through case study, questionnaire inquiry and interview methods, the opinion of scholars and experts, land and estate developers, government offices, and local residents, and then based on this understanding, tried to formulate a framework that would be appropriate for the rezoning system on land utilization in Taiwan. The study maintains that in implementing the rezoning system on land utilization, the most important principle is to respect the market function and endow the levy of rezoning with legal status. Then in conformity with this principle, complete and reasonable measures concerning the rezoning system on land utilization are to be constructed. This study suggests that, in a short period of time, the statute that governs the levy of rezoning, to name one ¡V Urban Planning law, be revised so that the rezoning system can gain legal ground and be implemented legally. At the same time, the negotiating mechanism for development permit should be strengthened so that the external cost influenced by development can be effectively included as the content for negotiation. For the long term, the central authority in charge should integrate the separate regulations on rezoning that belong to various offices in charge so as to establish a reasonable rezoning system on land utilization that conforms to the market function and to give this system a legal status. This status should be the basis for the implementation of this system. The applicant for alterations in land utilization should be the subject for the levy, and the levy should be executed in the form of cash donation, land donation and construction of public facilities. The government administration should be considered. For the levy amounts, calculation equations can be established as part of this system, and the concerned local government and the owner should negotiate to figure out the upper and lower limits of the estimated amount. The time to levy should be decided separately from the levy method, but they should match. With regard to the use, management and maintenance of rezoning items, the concerned local government should, according to the characteristics of rezoning items, establish accounts and authorities for special funds. These special funds should be only appropriated for improving, constructing, and managing the public facilities that have been influenced by alterations in land utilization. This perfect rezoning system on land utilization should enable the government, developer, and local residents to share land resources and harvest the plentiful fruit of perennial development.

Rowing exercise machines are the popular fitness goods with training the whole body, warm-up, and stretching. They have the advantages of promoting cardiopulmonary function, training muscles, and burning calories. The purpose of this work is to develop a systematic design procedure for the linkage-type rowing exercise machines. First, to investigate and discuss the rowing exercise machines and the rowing motion to induce the requirements and design tasks of rowing exercise machines. Then the design targets of this research are decided further in order to establish the design specification. Second, to carry out the creative design of rowing exercise machines by using the procedure of creative mechanism design. Third, to complete the kinematic design of rowing exercise machines. Computer software is utilized for the work of dimensional synthesis and kinematic analysis. Finally, to perform the embodiment design and to establish 3-D model drawing of the design solutions.

The Dalmatian is affected by deafness more than any other breed of domestic dog, with 30% of the United States population suffering from unilateral or bilateral deafness. The genetic origin of deafness in the Dalmatian is unknown. The objective of this work was to identify, using linkage analysis, any chromosomal region(s) in which the gene(s) responsible for deafness in the Dalmatian may be located. To achieve this objective it was necessary to 1) develop multiplexed microsatellite markers for an efficient whole genome scan, 2) assemble a multigenerational Dalmatian kindred segregating deafness, 3) estimate the heritability of deafness and perform complex segregation analysis, and 4) perform linkage analysis of deafness, and other phenotypic traits, in the Dalmatian kindred. A set of 172 microsatellite markers, termed Minimal Screening Set 1 (MSS1), was characterized, prior to this work, for whole genome scans of the domestic dog. 155 of the MSS1 markers were multiplexed into 48 multiplex sets. Amplification of the multiplex sets was achieved using a single thermal cycling program. The markers were labeled with fluorescent dyes and optimized for resolution on an ABI 310 Genetic Analyzer or ABI 377 Sequencer. A kindred of 266 Dalmatians was assembled, of which 199 had been diagnosed using the brainstem auditory evoked response to determine auditory status. Of these, 74.4% (N = 148) had normal hearing, 18.1% (N = 36) were unilaterally deaf, and 7.5% (N = 15) were bilaterally deaf. A heritability of 0.73 was estimated considering deafness a dichotomous trait and 0.75 as a trichotomous trait. Although deafness in the Dalmatian is clearly heritable, the evidence for the presence of a major gene affecting the disorder was not persuasive. Dalmatians (N = 117) from the assembled kindred were genotyped for the MSS1 markers (149 were polymorphic). Linkage analysis was performed for deafness, eye color, and spot color. The maximum LOD scores for deafness were found with markers Cos15 on CFA17 (LOD = 1.69) and FH2585 on CFA28 (LOD = 1.34). No significant linkage was found with eye color. Significant linkage for spot color was found with marker FH2319 (LOD = 9.7) on CFA11.

Thesis (Ph. D.)--University of Chicago, Committee on Genetics, June 2001. / Includes bibliographical references. Also available on the Internet.

Thesis (Ph. D.)--University of Washington, 2003. / Vita. Includes bibliographical references (p. 103-114).

Thesis (Ph. D.)--University of Washington, 2003. / Vita. Includes bibliographical references (p. 114-125).