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Recongurable computing technology has progressed to a stage where it is now possible to achieve orders of magnitude performance and power eciency gains over conventional computer architectures for a subset of high performance computing applications. In this thesis, we investigate the potential of recongurable computers to accelerate genomic sequence alignment specically for genome sequencing applications. We present a highly optimized implementation of a parallel sequence alignment algorithm for the Berkeley Emulation Engine (BEE2) recongurable computer, allowing a single BEE2 to align simultaneously hundreds of sequences. For each recongurable processor (FPGA), we demonstrate a 61X speedup versus a state-of-the-art implementation on a modern conventional CPU core, and a 56X improvement in performance-per-Watt. We also show that our implementation is highly scalable and we provide performance results from a cluster implementation using 32 FPGAs. We conclude that reconfigurable computers provide an excellent platform on which to run sequence alignment, and that clusters of recongurable computers will be able to cope far more easily with the vast quantities of data produced by new ultra-high-throughput sequencers.

There exist several challenges in supporting mobile applications. For example, creating a separate target application for each device type, leaving developers with a huge maintenance chore. Most desktop applications run on largely homogenous hardware so instead of writing the same code over and over again, developers only need to write modules to implement a particular need. This is because even though there are differences in PC hardware configurations, the same desktop application will work fine on any hardware as the operating system provides an abstract layer. This is the way mobile applications are expected to work. However, this has been divided into dozens of ill-assorted versions. Java mobile applications developers spend more time rewriting code to run on different versions of mobile devices more than they do actually creating application in the first place. This is an intolerable burden for small mobile developers, and it stifles mobile software innovation overall. Mobile devices differ in a variety of attributes, such as screen size, colour depth and the optional hardware devices they support such as cameras, GPS etc. The differences often require special code or project settings for successful deployment for each device a developer is targeting but this creates a huge logistical overhead. One potential solution that is shipped with NetBeans IDE is to add a new configuration for each device, modify the project properties, add some pre-processing code, then build and deploy the application. In most cases, one configuration for each distribution of the Java Archive (JAR) one plans to build for the project is created. For example, if a developer is planning to support three different screen sizes using two sets of vendor specific APIs, one needs to create six configurations. This reduces the performance of the application drastically and increases the size at the same time. This is not acceptable for mobile devices where memory size and processor performance are limited. The goal of this research work is to support mobile application development through a Java IDE (the NetBeans IDE in this case). Therefore, our approach will be to modify the NetBeans IDE to better address the difficulty that was mentioned above – namely targeting applications for different platforms. Our solution is to integrate another type of a preprocessor into the NetBeans IDE that will help alleviate the problems of the existing tool. Our approach is to directly implement this inside the NetBeans IDE to further support mobile application development with the NetBeans IDE.

There is no abstract available for this thesis.

Epidemiologic, laboratory and clinical data suggest that vitamin D plays a favourable role in the prevention and prognosis of prostate cancer (PCa) and other malignancies. However, the metabolism and function of vitamin D in tissues beyond those involved in bone metabolism are poorly understood. The objective of this thesis was to investigate whether higher levels of vitamin D consumed orally or achieved in the circulation result in increased concentrations of vitamin D metabolites in human tissue, and how this affects cellular biology. The hallmark of this work is a randomized clinical trial of oral vitamin D3 (400-, 10,000-, or 40,000 IU/d) in PCa patients to evaluate the effects of supplementation on prostatic vitamin D metabolism and on PCa pathology. Various methods to measure vitamin D metabolites in serum were evaluated and modified to allow for measurement of these metabolites in tissue. Ultimately, I developed a robust tissue extraction method coupled to enzyme immunoassay and liquid chromatography-tandem mass spectrometry for measurement of calcitriol hormone, as well as 25-hydroxyvitamin D (25(OH)D) and 24,25-dihydroxyvitamin D (24,25(OH)2D), respectively. Human colon tissue was analyzed first and found to contain calcitriol at physiologically relevant concentrations partly determined by serum calcitriol, with some evidence of local colonic synthesis. In the clinical trial, prostate tissue and serum levels of calcitriol, 25(OH)D and 24,25(OH)2D increased dose-dependently (p<0.02) without adverse side effects. The level of calcitriol attained in prostate tissue was inversely associated with the expression of Ki67 protein, a proliferation marker (p<0.05). Serum parathyroid hormone (PTH) and prostate specific antigen (PSA) declined from baseline in the combined higher-dose groups (10,000-40,000 IU/d) (p<0.02). We provide clinical trial evidence that prostatic vitamin D metabolism can be modulated in vivo by oral consumption of vitamin D3. Higher prostate calcitriol and vitamin D doses also showed suggestion of clinical benefit, including lowered Ki67 expression and modest reductions in serum PSA and PTH. Further studies are needed to validate the potential utility of dietary vitamin D3 supplementation in cancer prevention and therapy.

Epidemiologic, laboratory and clinical data suggest that vitamin D plays a favourable role in the prevention and prognosis of prostate cancer (PCa) and other malignancies. However, the metabolism and function of vitamin D in tissues beyond those involved in bone metabolism are poorly understood. The objective of this thesis was to investigate whether higher levels of vitamin D consumed orally or achieved in the circulation result in increased concentrations of vitamin D metabolites in human tissue, and how this affects cellular biology. The hallmark of this work is a randomized clinical trial of oral vitamin D3 (400-, 10,000-, or 40,000 IU/d) in PCa patients to evaluate the effects of supplementation on prostatic vitamin D metabolism and on PCa pathology. Various methods to measure vitamin D metabolites in serum were evaluated and modified to allow for measurement of these metabolites in tissue. Ultimately, I developed a robust tissue extraction method coupled to enzyme immunoassay and liquid chromatography-tandem mass spectrometry for measurement of calcitriol hormone, as well as 25-hydroxyvitamin D (25(OH)D) and 24,25-dihydroxyvitamin D (24,25(OH)2D), respectively. Human colon tissue was analyzed first and found to contain calcitriol at physiologically relevant concentrations partly determined by serum calcitriol, with some evidence of local colonic synthesis. In the clinical trial, prostate tissue and serum levels of calcitriol, 25(OH)D and 24,25(OH)2D increased dose-dependently (p<0.02) without adverse side effects. The level of calcitriol attained in prostate tissue was inversely associated with the expression of Ki67 protein, a proliferation marker (p<0.05). Serum parathyroid hormone (PTH) and prostate specific antigen (PSA) declined from baseline in the combined higher-dose groups (10,000-40,000 IU/d) (p<0.02). We provide clinical trial evidence that prostatic vitamin D metabolism can be modulated in vivo by oral consumption of vitamin D3. Higher prostate calcitriol and vitamin D doses also showed suggestion of clinical benefit, including lowered Ki67 expression and modest reductions in serum PSA and PTH. Further studies are needed to validate the potential utility of dietary vitamin D3 supplementation in cancer prevention and therapy.

This study highlights three main concerns in relation to history teaching in Turkish secondary schools. The first one investigates student and practising history teachers' and history teacher educators' views on the existing Turkish secondary school history curriculum and its implementation. The second concern is to explore the perspectives of the same population about Europe and the European dimension in history teaching. The last one deals with their suggestions on the improvement of the history curriculum with the potential inclusion of the European dimension. These issues are considered important, because the recent political developments accelerating the process of Turkey's integration into Europe indicated the necessity for preparing the Turkish public for this purpose. History teaching in schools is one of the channels to prepare Turkish youth to take a part in Europe through developing their perspectives and abilities. The methodological design of the study embraces both quantitative and qualitative research methods. Questionnaires were completed by student teachers, practising teachers and teacher educators from various secondary schools and three universities in Turkey. Semi-structured interviews were carried out with a small number of participants selected from the above three groups. The data are analysed to find out the participants' general views about the issues mentioned above as well as the similarities and differences amongst the views of the three participating groups and between student teacher and teacher educator participants from the three universities. The results of the study show that most of the participants are critical of the existing curriculum and the current practice of history teaching. Their criticism focuses on the presentation of the aims and objectives of the curriculum, the selection of curriculum content and pedagogical problems. According to the research findings, the presentation of Europe and European history in the current curriculum is inadequate. Furthermore, the participants' disclosed varying views about European matters, but their positive views about Europe related issues and a potential inclusion of the ED in history teaching observed were encouraging. Based on the suggestions of the participants, it is argued that the Turkish secondary school history curriculum needs to be improved by including a European dimension. Specifically, the aims and objectives of history teaching, the criteria for the selection of curriculum content, pedagogy and history teacher education programmes should be shifted from the existing traditional approach to the new critical and skill-based approaches. In other words, this study argues that the purpose of history teaching is not to develop a particular identity or citizenship consciousness through the transmission of predetermined content knowledge. Instead, it suggests that history should be taught to enable learners to develop historical and critical thinking skills through exercising and utilising the methodology of history, which help them orientate themselves in local, national, European and global contexts.

Ethel Carnie Holdsworth confronted the problems faced by the British working class in the early twentieth century in a fresh way. She believed that writing could change attitudes, and between 1907 and 1931 she endeavoured to practice that conviction through journalism, poetry and fiction in order to make her dream of a fairer society come true. Despite working in Lancashire cotton mills from 1897 when she was eleven, until the end of the First World War, she established a substantial audience for her views in the popular press and through romantic novels, and supported the impact she made in this way by verse, the use of film as propaganda, and involvement in the work of forgotten political groups like the British Citizen Party and the National Union for Combating Fascism. This study describes Ethel Carnie Holdsworth's experiments in mass communication and it assesses the influence she had on contemporary debates about the meaning of freedom in the 1910s and 1920s. In doing so it reveals new perspectives on the position of women in society, on the attempts of the Labour movement to improve the lot of the working class, and on the fight against fascism. The argument made here is that an understanding of early twentieth century political history is revised and enriched by the incorporation of an unusual working-class voice which is expressed in forms that give Ethel Carnie Holdsworth's work an immediacy and difference. It is presented here as a biography because the circumstances she had to overcome make her effort worthy of celebration, and her achievement a rare and valuable commentary on her times.