Role Of Transition Metal Ions And Redox Activity In The Development Of Atherosclerotic Plaques
Funder
National Health and Medical Research Council
Funding Amount
$196,018.00
Summary
Metal ions such as iron and copper have been reproted to be present in the lesions present in diseased human arteries and it has been suggested that these metal ions contribute to the development of atherosclerosis (hardening of the arteries) via their ability to catalyse the formation of highly reactive molecualr fragments called free radicals. Though metal ions are known to catalyse such reactions in test-tube experiments, both the presence of metal ions in diseased arteries and their ability ....Metal ions such as iron and copper have been reproted to be present in the lesions present in diseased human arteries and it has been suggested that these metal ions contribute to the development of atherosclerosis (hardening of the arteries) via their ability to catalyse the formation of highly reactive molecualr fragments called free radicals. Though metal ions are known to catalyse such reactions in test-tube experiments, both the presence of metal ions in diseased arteries and their ability to generate free radicals is controversial. This study will employ a novel, minimally-invasive, technique to assess the nature and quantity of metal ions present in well-defined human and animal lesions at different stages of lesion development. The ability of these metal ions to catalyse free radical formation from components present in the artery wall will also be assessed. The release of these metal ions from the artery wall to added organic molecules will be assessed as this might minimise their potential to cause damage, and provide a possible therapeutic strategy. These studies will therefore provide valuable information as to the significance and role of reactive metal ions in the development of human artery disease and the possible prevention, or minimisation, of such processes.Read moreRead less
Mitochondrial Iron Overload And Friedreich's Ataxia: The Role Of Frataxin In Iron And Haem Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$606,000.00
Summary
Friedreich's ataxia (FA) is due to the lack of a protein known as frataxin. A variety of studies using Baker's yeast and conditional frataxin knockout (KO) mice have shown that deletion of frataxin leads to the accumulation of toxic iron in their mitochondrion. More recently, a variety of studies have shown that FA patients have iron-loading within their mitochondrion. Iron in the highly redox active environment of the mitochondrion could contribute to the generation of cytotoxic radicals that c ....Friedreich's ataxia (FA) is due to the lack of a protein known as frataxin. A variety of studies using Baker's yeast and conditional frataxin knockout (KO) mice have shown that deletion of frataxin leads to the accumulation of toxic iron in their mitochondrion. More recently, a variety of studies have shown that FA patients have iron-loading within their mitochondrion. Iron in the highly redox active environment of the mitochondrion could contribute to the generation of cytotoxic radicals that cause severe damage. Further, cells deficient in frataxin are sensitive to oxidant stress and Fe chelators rescue oxidant-mediated death of cells from FA patients. Indeed, free radical scavengers have shown to be of use in the treatment of this disease. Studies in DR's lab during this NHMRC grant have shown that frataxin is down-regulated by erythroid differentiation or the haem precursor, protoporphyrin IX (BLOOD 2002;99:3813-22). These data indicate a role for frataxin in Fe metabolism and the pathogenesis of FA. In this study we will continue to examine the role of frataxin in the way cells handle Fe using experimental models developed under the current NHMRC grant. These include transfected cell lines with low frataxin expression generated using an expression vector containing anti-sense frataxin cDNA. Further we obtained the frataxin conditional KO mouse and generated a breeding colony. These animals display many of the pathological features of FA and are the best current model of the disease. Indeed, they will be critical for assessing the role of frataxin in Fe metabolism and as a model to test the ability of Fe-binding drugs to prevent the pathology observed. We designed lipid-soluble chelators that can enter the mitochondrion to bind Fe (Biochim Biophys Acta 2001;1536:133-140) and these ligands will be tested to prevent disease progression in the KO mice. This exciting research is crucial for understanding the pathogenesis of FA and in creating new therapies.Read moreRead less
Harmonic analysis of rough oscillations. This project intends to explore new perspectives in harmonic analysis. Harmonic analysis is a set of mathematical techniques used in many branches of science and engineering to analyse complex signals (functions). It is highly effective in modelling phenomena such as the propagation of electromagnetic waves, but it is currently limited to propagation occurring in a simple-enough medium. An intense international research effort in harmonic analysis is curr ....Harmonic analysis of rough oscillations. This project intends to explore new perspectives in harmonic analysis. Harmonic analysis is a set of mathematical techniques used in many branches of science and engineering to analyse complex signals (functions). It is highly effective in modelling phenomena such as the propagation of electromagnetic waves, but it is currently limited to propagation occurring in a simple-enough medium. An intense international research effort in harmonic analysis is currently under way to lift this limitation. This project is part of that effort, and aims to unite two of its fundamental directions of development: one focusing on the roughness of the medium; and one focusing on the interaction between highly oscillatory aspects of the function and the geometry of the medium.Read moreRead less
ARC Financial Integrity Research Network. The integrity of the financial system is constantly under stress because of the development of ever more complex financial instruments, structures and strategies, and the associated research technologies that continues to accelerate worldwide. FIRN's vision is to harness the considerable strengths of Australia's internationally renowned finance, accounting and economics researchers into a research agenda to address issues concerning the integrity of the ....ARC Financial Integrity Research Network. The integrity of the financial system is constantly under stress because of the development of ever more complex financial instruments, structures and strategies, and the associated research technologies that continues to accelerate worldwide. FIRN's vision is to harness the considerable strengths of Australia's internationally renowned finance, accounting and economics researchers into a research agenda to address issues concerning the integrity of the financial system. It will enable Australian research in this area to match the scale and impact of similar research in other major international financial centres, and play an essential role in placing Australia among the world's leaders in financial markets related research.Read moreRead less
Investment Approaches and Applications in Financial Markets: Evolutionary Kernel Based Subset Time-Series Using Semi-Parametric Approaches. The project will develop new investment assessments based on subset time-series modeling. Innovative evolutionary kernel smoothing algorithms using semi-parametric approaches will be introduced. The project will make three important applications of this modeling in financial markets: a) benchmarking and evaluation of inflation-indexed bonds; b) evaluation of ....Investment Approaches and Applications in Financial Markets: Evolutionary Kernel Based Subset Time-Series Using Semi-Parametric Approaches. The project will develop new investment assessments based on subset time-series modeling. Innovative evolutionary kernel smoothing algorithms using semi-parametric approaches will be introduced. The project will make three important applications of this modeling in financial markets: a) benchmarking and evaluation of inflation-indexed bonds; b) evaluation of the performance of global diversified investment funds; and c) prediction to provide early warning of the emergence of destabilising deflation or inflation. These three applications will lead to improved risk management practices and investment performance. Recursive algorithms will provide new statistical methods to study investment asset price movements and market volatility.
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Helping Central Banks Measure Unobserved Variables Using Real-time Forecasts. The project addresses structural measurement problems confronted routinely by central bankers. The techniques developed, and the estimates provided, will aid directly the Partner Organisations (the Reserve Bank of Australia, the Reserve Bank of New Zealand and Norges Bank) and other central banks in formulating monetary policy. The analysis will allow interest rates in Australia and elsewhere to be set with greater pre ....Helping Central Banks Measure Unobserved Variables Using Real-time Forecasts. The project addresses structural measurement problems confronted routinely by central bankers. The techniques developed, and the estimates provided, will aid directly the Partner Organisations (the Reserve Bank of Australia, the Reserve Bank of New Zealand and Norges Bank) and other central banks in formulating monetary policy. The analysis will allow interest rates in Australia and elsewhere to be set with greater precision. The techniques developed in this project will facilitate the understanding and communication of monetary policy within the central banks concerned, and enhance communication of monetary policy strategy to the public.Read moreRead less
Investment approaches and opportunities in renewable energy and financial resource markets, using semi-parametric approaches to evolutionary subset time-series lattice-ladder modelling. The project findings will help Australian exporters and importers understand and manage energy and resource price risks more effectively. The investment community will benefit through selecting optimal asset allocations and enhancing value to investors. It will also benefit many other agencies, particularly in th ....Investment approaches and opportunities in renewable energy and financial resource markets, using semi-parametric approaches to evolutionary subset time-series lattice-ladder modelling. The project findings will help Australian exporters and importers understand and manage energy and resource price risks more effectively. The investment community will benefit through selecting optimal asset allocations and enhancing value to investors. It will also benefit many other agencies, particularly in the service industries. It is not well recognised that in developed countries, including Australia, the financial service and related sectors account for more than 60 percent of economic activity and employment, so it is critical that more sophisticated statistical methods be established, and practical applications conducted, in order to advance the understanding of complexity management in the financial service and related sectors.Read moreRead less
Special Research Initiatives - Grant ID: SR0354466
Funder
Australian Research Council
Funding Amount
$20,000.00
Summary
Mathematics in Contemporary Science. The Mathematics in Contemporary Science Research Network brings contemporary methods of non-linear analysis and differential equations, geometric reasoning and relevant algebraic and topological ideas to enrich six application areas in modern science: Complex Systems, Computer Vision, Optimal Transportation, Nanotechnology, Physics and Shortest Networks. MiCS will develop both the mathematics and the application areas in parallel. It will focus on postgradu ....Mathematics in Contemporary Science. The Mathematics in Contemporary Science Research Network brings contemporary methods of non-linear analysis and differential equations, geometric reasoning and relevant algebraic and topological ideas to enrich six application areas in modern science: Complex Systems, Computer Vision, Optimal Transportation, Nanotechnology, Physics and Shortest Networks. MiCS will develop both the mathematics and the application areas in parallel. It will focus on postgraduate training through workshops, summer schools and web based resources and build long-term international collaborations with EU networks and NSERC, NSF and EPSRC institutes as well as bringing together academic and industry leaders.Read moreRead less
Inequality, Prosperity and the Australian Welfare State. This project aims to clarify contested understandings of Australian inequality and the role of economic and social policies in addressing policy challenges going forward. The objective of the project is to generate significantly improved knowledge of inequality in Australia using innovative approaches of data splicing, decomposition, simulation and backcasting to fill research gaps and resolve contested interpretations. We aim to provide a ....Inequality, Prosperity and the Australian Welfare State. This project aims to clarify contested understandings of Australian inequality and the role of economic and social policies in addressing policy challenges going forward. The objective of the project is to generate significantly improved knowledge of inequality in Australia using innovative approaches of data splicing, decomposition, simulation and backcasting to fill research gaps and resolve contested interpretations. We aim to provide a benchmark and robust framework against which policy development after the current crisis can be evaluated. This project aims to provide significant benefits, keeping Australia at the forefront of research on inequality and public policy, strengthening links between researchers and policy makers.
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Power systems with diverse generation - implications, control and capability. This research will generate a systematic methodology to handle the impact of the renewable energy sources on the NSW power grid. It increases our understanding of the impact of climate change policies relating to mandatory targets for greenhouse gas reduction helping to build Australia’s research capacity in the national priority area of an environmentally sustainable Australia. The anticipated methodology can also be ....Power systems with diverse generation - implications, control and capability. This research will generate a systematic methodology to handle the impact of the renewable energy sources on the NSW power grid. It increases our understanding of the impact of climate change policies relating to mandatory targets for greenhouse gas reduction helping to build Australia’s research capacity in the national priority area of an environmentally sustainable Australia. The anticipated methodology can also be seen as protecting the security of power infrastructure as well. Maintaining a critical energy infrastructure protects our way of life and ensures ongoing social, economic and environmental well being of Australia.Read moreRead less