Typescript. / Thesis (Ph. D.)--University of Hawaii at Manoa, 1972. / Bibliography: leaves 91-96. / ix, 96 l illus

Typescript. / Thesis (Ph. D.)--University of Hawaii, 1961. / Bibliography: leaves [118]-123. / v, 123 leaves ill., map, diagrs

Understanding the binding specificity of transcription factors is an important step towards accurate computational prediction of regulatory sequences governing gene expression. Higher-throughput binding site characterization methods have long been available in the laboratory for the study of protein-DNA interactions in solution or upon a surface. In this thesis a new method is introduced for characterization of inducible regulatory sequences in living cells based on construction and analysis of promoter-reporter gene plasmids. Spiked oligonucleotides are used to generate libraries of regulatory sequences with subtle variations from a known regulatory element. Screening of the library in cell culture for the capacity of the mutated sequences to mediate expression provides a diverse collection of responsive and non-responsive sequences to aid in understanding the sequence requirement for an inducible transcription factor binding site. We apply the methodology to the study of antioxidant responsive elements, the target sites of the Nfe212 transcription factor. These target sequences commonly found in the promoters of detoxification genes modulate gene expression in response to a diverse array of chemicals. The variants serve as a primary screen for future targeted mutational analysis to further characterize context-specific sequence requirement in the ARE and/or interdependence between positions. Moreover, a transcription factor binding profile can be generated from functional ARE variants in the library screen. Such an ARE profile performs as well as standard profiles based on bona fide ARE sequences drawn from the scientific literature.

Human cytomegalovirus (HCMV) is a ubiquitous virus that causes significant morbidity and mortality in immunocompromised individuals. Although there are prophylactic treatments available, all current antiviral drugs ultimately target the DNA polymerase, resulting in the increasing emergence of antiviral resistant strains in the clinical setting. There is a fundamental need for understanding the role of other essential genes in DNA replication as a foundation for developing new antiviral treatments that are safe and which utilize a mechanism of action different to existing therapies. In this study we looked at six HCMV replication genes encoding for the DNA polymerase accessory protein (UL44), single stranded DNA binding protein (UL57), primase (UL70), helicase (UL105), primase-helicase associated protein (UL102), and the putative initiator protein (UL84) in order to increase our understanding of their role in DNA replication. The aim of this project was to identify variation within these genes as well as to predict putative domains and motifs in order to ultimately express and study the functional properties of the HCMV primase (UL70) through the use of recombinant mutants. Sequencing of these genes revealed a high degree of conservation between the isolates with amino acid sequence identity of >97% for all genes. Using ScanProsite software from the Expert Protein Analysis System (ExPASy) proteomics server, we have mapped putative motifs throughout these HCMV replication genes. In particular, highly conserved putative Nlinked glycosylation sites were identified in UL105 that were also conserved across 33 homologues as well as several unique motifs including casein kinase II phosphorylation sites (CKII) in UL105 and UL84, a microbodies signal motif in UL57 and an integrin binding site in the UL102 helicase-primase associated protein. Our investigations have also elucidated motif-rich regions of the UL44 DNA polymerase accessory protein, mapped functionally important domains of the UL105 helicase and identified cysteine motifs that have implications for folding of the UL70 primase. Taken together, these findings provide insights to regions of these HCMV replication proteins that are important for post-translation modification, activation and overall function, and this information can be utilized to target further research into these proteins and advance the development of novel antiviral agents that target these processes.

Since its first use in criminal investigations in 1987, DNA profiling has become the new gold standard for investigations and prosecutions. Academics, politicians and law enforcement officials have presented DNA evidence as a ??scientific hero?? that is capable of solving crimes and preventing miscarriages of justice. However, in spite of this reputation, few studies have explored the impact of this technology on criminal justice practitioners, or on the process of investigating and processing criminal offences. This dissertation provides a comparative study of the use of DNA profiling in two jurisdictions: New South Wales (NSW) in Australia and the Thames Valley in the United Kingdom (UK). Interviews canvassed the perspectives and experiences of police officers, scene of crime officers (SOCOs), forensic scientists, criminal lawyers, and judicial officers from these areas. These interviews were analysed in conjunction with appeal judgments and police statistics to reveal how DNA evidence has been used in the NSW and Thames Valley. The research presented in this dissertation indicates that DNA profiling is having a number of far-reaching effects on both criminal justice systems and is seen as a reliable forensic tool by criminal justice practitioners. Practitioners routinely use DNA evidence throughout the various stages of the criminal justice process and are actively changing their practices to utilise the technology more effectively. One of the main impacts of the introduction of DNA evidence into criminal investigations has been the need to provide substantial resources and infrastructure for the collection, analysis, and storage of samples. Both jurisdictions encountered a number of problems because they provided insufficient resources to effectively use DNA profiling. This study also offers insight into how criminal justice practitioners perceive the dangers of using DNA evidence and how miscarriages of justice can occur. Finally, through an analysis of the combined experiences of criminal justice practitioners, this dissertation challenges the widespread acceptance and routine use of forensic DNA profiling. It further suggests that it is now time to re-consider current practices in relation to how resources are devoted to the technology, and how criminal justice practitioners are using the technology.

Copies of author's previously published article inserted onto back cover. / Bibliography: leaves 164-187. / xxii, 187, [87] leaves, [18] leaves of plates : ill. (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Confirms the value of DHBV infection in ducks as a model to evaluate the protective and therapeutic efficacy of DNA vaccines against hepadnavirus infection. The possibility that this model could be explored further to evaluate various combinations of antigens and cytokines 'cocktail' DNA vaccines that elicit the most effective humoral and effective CMI responses for prevention and treatment of HBV infection is discussed. / Thesis (Ph.D.)--University of Adelaide, Dept. of Microbiology and Immunology, 1999

Typewritten / 117 leaves, [28] leaves of plates : ill. ; 27 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Physical & Inorganic Chemistry,1960

Copies of author's previously published article inserted onto back cover. / Bibliography: leaves 164-187. / xxii, 187, [87] leaves, [18] leaves of plates : ill. (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Confirms the value of DHBV infection in ducks as a model to evaluate the protective and therapeutic efficacy of DNA vaccines against hepadnavirus infection. The possibility that this model could be explored further to evaluate various combinations of antigens and cytokines 'cocktail' DNA vaccines that elicit the most effective humoral and effective CMI responses for prevention and treatment of HBV infection is discussed. / Thesis (Ph.D.)--University of Adelaide, Dept. of Microbiology and Immunology, 1999

Proefschrift Universiteit van Amsterdam. / Met samenvatting in het Nederlands.

Thesis (Ph.D.)-Tufts University, 2002. / Adviser: Clemens Richert. Submitted to the Dept. of Chemistry. Includes bibliographical references (leaves 146-150). Access restricted to members of the Tufts University community. Also available via the World Wide Web;