Cardiovascular disease and cancer are the two most common causes of death worldwide. Angiogenesis plays a critical role tumourigenesis and atherogenesis. As a member of the basic region-leucine zipper protein family, c-Jun, has been linked with cell proliferation, migration and cell survival. However, the relationship between c-Jun and angiogenesis has not been firmly established. In this thesis, strategies targeting c-Jun mRNA such as DNAzyme and siRNA have been designed and evaluated for their ability to inhibit the c-Jun mRNA and c-Jun protein expression in vitro and in vivo. These agents block c-Jun expression and inhibit DNA binding activity of c-Jun. Luciferase assay showed that c-Jun siRNA suppressed c-Jun/AP-1-dependent reporter activity. The processes of cell proliferation, migration, invasion and tube formation were all down-regulated after treatment with c-Jun targeting agents. In vivo, c-Jun DNAzymes and siRNA inhibit angiogenesis in multiple models of angiogenesis in multiple models of angiogenesis, including tumour angiogenesis and growth, matrix angiogenesis, corneal angiogenesis and retinal neovascularization. This is mediated, at least in part, by c-Jun siRNA or DNAzyme inhibition of MMP-2 expression. These findings demonstrate the critical role played by c-Jun in the involvement of neovascularization and suggest that DNAzymes or siRNAs are efficient gene-silencing agents. The ability to identify and control key genes in angiogenesis provides opportunities for developing therapeutic molecular tools to treat cancer or other angiogenesis related diseases.

Cardiovascular disease and cancer are the two most common causes of death worldwide. Angiogenesis plays a critical role tumourigenesis and atherogenesis. As a member of the basic region-leucine zipper protein family, c-Jun, has been linked with cell proliferation, migration and cell survival. However, the relationship between c-Jun and angiogenesis has not been firmly established. In this thesis, strategies targeting c-Jun mRNA such as DNAzyme and siRNA have been designed and evaluated for their ability to inhibit the c-Jun mRNA and c-Jun protein expression in vitro and in vivo. These agents block c-Jun expression and inhibit DNA binding activity of c-Jun. Luciferase assay showed that c-Jun siRNA suppressed c-Jun/AP-1-dependent reporter activity. The processes of cell proliferation, migration, invasion and tube formation were all down-regulated after treatment with c-Jun targeting agents. In vivo, c-Jun DNAzymes and siRNA inhibit angiogenesis in multiple models of angiogenesis in multiple models of angiogenesis, including tumour angiogenesis and growth, matrix angiogenesis, corneal angiogenesis and retinal neovascularization. This is mediated, at least in part, by c-Jun siRNA or DNAzyme inhibition of MMP-2 expression. These findings demonstrate the critical role played by c-Jun in the involvement of neovascularization and suggest that DNAzymes or siRNAs are efficient gene-silencing agents. The ability to identify and control key genes in angiogenesis provides opportunities for developing therapeutic molecular tools to treat cancer or other angiogenesis related diseases.

Falls risk factor assessment is the first step in the development of appropriate intervention strategies for the prevention of falls. However, few multifactorial, validated falls risk assessments exist which are suitable for use in busy clinical settings. This project aimed to develop a reliable and valid falls risk assessment that was feasible for use in various clinical settings. The QuickScreen Clinical Falls Risk Assessment was developed and evaluated via four methods; a) the test-retest reliability of the measures was assessed with 30 community-dwelling older people, b) the concurrent validity of the measures was assessed by comparison with performance in the Physiological Profile Assessment, c) the predictive validity of the measures was assessed by comparison of performance with prospective falls in two studies involving large samples of community dwelling older people and d) the feasibility of the assessment was evaluated with 40 clinicians who trialled the assessment with their patients. The QuickScreen clinical falls risk assessment consists of eight measures, including previous falls, total medications, psychoactive medications, visual acuity, touch sensation, the sit to stand test, the near tandem stand test and the alternate step test. The test-retest reliability of the assessment measures was acceptable (intraclass correlation coefficients ranged from 0.56 to 0.89) and the assessment measures discriminated between multiple fallers and non-multiple fallers with relative risk values ranging from 1.4 to 2.5. The clinicians that trialled the assessment reported that it was quick and easy to administer and that it assisted in the management of their elderly patients. These results show that the QuickScreen Clinical Falls Risk Assessment has proven validity, test-retest reliability and is practical for use in a variety of clinical settings.

Falls risk factor assessment is the first step in the development of appropriate intervention strategies for the prevention of falls. However, few multifactorial, validated falls risk assessments exist which are suitable for use in busy clinical settings. This project aimed to develop a reliable and valid falls risk assessment that was feasible for use in various clinical settings. The QuickScreen Clinical Falls Risk Assessment was developed and evaluated via four methods; a) the test-retest reliability of the measures was assessed with 30 community-dwelling older people, b) the concurrent validity of the measures was assessed by comparison with performance in the Physiological Profile Assessment, c) the predictive validity of the measures was assessed by comparison of performance with prospective falls in two studies involving large samples of community dwelling older people and d) the feasibility of the assessment was evaluated with 40 clinicians who trialled the assessment with their patients. The QuickScreen clinical falls risk assessment consists of eight measures, including previous falls, total medications, psychoactive medications, visual acuity, touch sensation, the sit to stand test, the near tandem stand test and the alternate step test. The test-retest reliability of the assessment measures was acceptable (intraclass correlation coefficients ranged from 0.56 to 0.89) and the assessment measures discriminated between multiple fallers and non-multiple fallers with relative risk values ranging from 1.4 to 2.5. The clinicians that trialled the assessment reported that it was quick and easy to administer and that it assisted in the management of their elderly patients. These results show that the QuickScreen Clinical Falls Risk Assessment has proven validity, test-retest reliability and is practical for use in a variety of clinical settings.

This thesis concerns domestic violence in New Zealand. Its aim is to help find effective ways of preventing domestic violence in our homes through community level public education/awareness interventions. Domestic violence has a damaging effect within a large number of New Zealand households; the primary aim of this thesis is to contribute research to the efforts in New Zealand directed at preventing domestic violence.This thesis situates domestic violence within both a sociological and theoretical framework as well as within the context of New Zealand public education campaigns. Central to this thesis is a critical analysis of one particular community level public education and awareness intervention that was implemented in the United States throughout the 1990s. The core community-level principles of this US project have been analysed with regard to the suitability of integrating them into a hypothetical domestic violence public awareness campaign in New Zealand (one that would aim to help victims seek appropriate help from their situation).This US community level intervention was called the AIDS Community Demonstration Project (ACDP), its aim being to increase HIV risk reduction behaviours amongst at-risk people within the community. It is acknowledged throughout this thesis that the risk of HIV infection and the nature of domestic violence are very different issues although both are key health issues. However, the analysis of the ACDP was chosen predominantly because of the broad community focussed principles that it followed. The core research question of this thesis is as follows: Are the broad principles used within the ACDP suitable to be integrated into a victim-based domestic violence public awareness campaign in New Zealand? If so, to what extent? If not, why?My critical analysis has been informed by qualitative interviews with key experts in the field of domestic violence prevention in New Zealand. This critical analysis has highlighted a number of key elements in the complex task of domestic violence prevention and discusses the measures needed to sustain an abuse-free New Zealand.

Cardiovascular disease and cancer are the two most common causes of death worldwide. Angiogenesis plays a critical role tumourigenesis and atherogenesis. As a member of the basic region-leucine zipper protein family, c-Jun, has been linked with cell proliferation, migration and cell survival. However, the relationship between c-Jun and angiogenesis has not been firmly established. In this thesis, strategies targeting c-Jun mRNA such as DNAzyme and siRNA have been designed and evaluated for their ability to inhibit the c-Jun mRNA and c-Jun protein expression in vitro and in vivo. These agents block c-Jun expression and inhibit DNA binding activity of c-Jun. Luciferase assay showed that c-Jun siRNA suppressed c-Jun/AP-1-dependent reporter activity. The processes of cell proliferation, migration, invasion and tube formation were all down-regulated after treatment with c-Jun targeting agents. In vivo, c-Jun DNAzymes and siRNA inhibit angiogenesis in multiple models of angiogenesis in multiple models of angiogenesis, including tumour angiogenesis and growth, matrix angiogenesis, corneal angiogenesis and retinal neovascularization. This is mediated, at least in part, by c-Jun siRNA or DNAzyme inhibition of MMP-2 expression. These findings demonstrate the critical role played by c-Jun in the involvement of neovascularization and suggest that DNAzymes or siRNAs are efficient gene-silencing agents. The ability to identify and control key genes in angiogenesis provides opportunities for developing therapeutic molecular tools to treat cancer or other angiogenesis related diseases.

Cardiovascular disease and cancer are the two most common causes of death worldwide. Angiogenesis plays a critical role tumourigenesis and atherogenesis. As a member of the basic region-leucine zipper protein family, c-Jun, has been linked with cell proliferation, migration and cell survival. However, the relationship between c-Jun and angiogenesis has not been firmly established. In this thesis, strategies targeting c-Jun mRNA such as DNAzyme and siRNA have been designed and evaluated for their ability to inhibit the c-Jun mRNA and c-Jun protein expression in vitro and in vivo. These agents block c-Jun expression and inhibit DNA binding activity of c-Jun. Luciferase assay showed that c-Jun siRNA suppressed c-Jun/AP-1-dependent reporter activity. The processes of cell proliferation, migration, invasion and tube formation were all down-regulated after treatment with c-Jun targeting agents. In vivo, c-Jun DNAzymes and siRNA inhibit angiogenesis in multiple models of angiogenesis in multiple models of angiogenesis, including tumour angiogenesis and growth, matrix angiogenesis, corneal angiogenesis and retinal neovascularization. This is mediated, at least in part, by c-Jun siRNA or DNAzyme inhibition of MMP-2 expression. These findings demonstrate the critical role played by c-Jun in the involvement of neovascularization and suggest that DNAzymes or siRNAs are efficient gene-silencing agents. The ability to identify and control key genes in angiogenesis provides opportunities for developing therapeutic molecular tools to treat cancer or other angiogenesis related diseases.

Master of Dental Surgery / This work was digitised and made available on open access by the University of Sydney, Faculty of Dentistry and Sydney eScholarship . It may only be used for the purposes of research and study. Where possible, the Faculty will try to notify the author of this work. If you have any inquiries or issues regarding this work being made available please contact the Sydney eScholarship Repository Coordinator - ses@library.usyd.edu.au

Diss. (sammanfattning) Uppsala : Univ., 2001. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.