NMR Of Red Cells: Plasma Membrane Oxidoreductase, And Cation Transport
Funder
National Health and Medical Research Council
Funding Amount
$192,388.00
Summary
An interesting paradox exists with respect to the 'central' function of the red blood cell (RBC): it delivers the main oxidising capacity to the body (O2), but it also carries the chemically opposite functionality in its membrane, namely reducing capacity. The reduction of many oxidised proteins and metabolites in blood plasma is mediated by a plasma-membrane oxido-reductase (PMOR). Ascorbic acid (vitamin C) dramatically accelerates this rate of reduction but its precise molecular role is unknow ....An interesting paradox exists with respect to the 'central' function of the red blood cell (RBC): it delivers the main oxidising capacity to the body (O2), but it also carries the chemically opposite functionality in its membrane, namely reducing capacity. The reduction of many oxidised proteins and metabolites in blood plasma is mediated by a plasma-membrane oxido-reductase (PMOR). Ascorbic acid (vitamin C) dramatically accelerates this rate of reduction but its precise molecular role is unknown; neither is the immediate source of the reducing equivalents (electrons) known. Novel, non-invasive, 13C NMR methods have been developed, and others are planned in this project, to study the rate of reduction of Otest? compounds, including 13C-ferricyanide, and reactions of 13C-ascorbate. This will provide a quantitative understanding of the kinetics of the redox reactions in the intact cell. The transfer of negative charges (electrons) from the cell, in the longer term (minutes) inevitably must be matched by the movement of cations (positive charges). The main cation flux is mediated by Na+, K+-ATPase, but various cation exchange pathways are also involved in the total Oionic economy? of the cell. Of special interest will be the calcium-activated K+ (or Gardos) channel. This Oopens? inappropriately in malaria, sickle cell anaemia, and under blood bank storage conditions, and this is thought to be the basis of some of the pathological events in these conditions. The alkali-metal cation exchange pathway ( Na+-Li+) is more activate in the red cells of many patients with hypertension. So, multiple-quantum NMR methods will be used to monitor membrane transport and binding of cations to characterise the kinetics and regulation of the K+-channel, and the Na+-Li+ exchange reactions. The significance will lie in a basic understanding of, and possible 'diagnostic methods' for the biochemical processes that occur in red blood cells in health and disease.Read moreRead less
Behavioural responses to transport congestion: peak spreading and the more efficient usage of transport infrastructure. Transport networks in cities such as Sydney are at or near capacity. It is no longer socially, environmentally or financially sustainable to continue supplying additional transport infrastructure to meet increased demand. An alternative is to make better use of existing infrastructure by spreading demand more evenly across the day. This project will test behavioural responses t ....Behavioural responses to transport congestion: peak spreading and the more efficient usage of transport infrastructure. Transport networks in cities such as Sydney are at or near capacity. It is no longer socially, environmentally or financially sustainable to continue supplying additional transport infrastructure to meet increased demand. An alternative is to make better use of existing infrastructure by spreading demand more evenly across the day. This project will test behavioural responses to increased congestion and quantify the phenomenon of peak spreading. It will assess economic costs and benefits of using congestion as a signal to encourage more efficient network usage, and examine other tools (e.g. time-based transport pricing) to encourage more efficient use of transport infrastructure.Read moreRead less
Multidimensional evaluation of the overall benefits of voluntary travel behaviour change programs. Voluntary Travel Behaviour Programs (VTBC) offer considerable promise for the management of traffic congestion and reduction in greenhouse gas and air quality emissions from road transport. Research to date has identified two outstanding issues: (1) measurement and evaluation of actual behaviour change and (2) identification of the full benefits and impacts of VTBC. Empirical studies indicate that ....Multidimensional evaluation of the overall benefits of voluntary travel behaviour change programs. Voluntary Travel Behaviour Programs (VTBC) offer considerable promise for the management of traffic congestion and reduction in greenhouse gas and air quality emissions from road transport. Research to date has identified two outstanding issues: (1) measurement and evaluation of actual behaviour change and (2) identification of the full benefits and impacts of VTBC. Empirical studies indicate that many of the benefits fall outside the transport area, including a wide range of socio-economic benefits to individuals and the community. This project will develop a survey tool for assessing benefits and impacts of VTBC within a properly designed and tested evaluation framework.Read moreRead less
Promoting active travel and public transport for a post-pandemic world. In many major cities, COVID-19 stimulated the provision of open streets, pop up bike lanes and widened pedestrian access, prompting unprecedented increases cycling and walking. While this type of infrastructure has always been supported by urban planners and designers, the pandemic has served as a vital inflection point, enabling cities to pursue long-term sustainable transport initiatives, including investment in Active Tra ....Promoting active travel and public transport for a post-pandemic world. In many major cities, COVID-19 stimulated the provision of open streets, pop up bike lanes and widened pedestrian access, prompting unprecedented increases cycling and walking. While this type of infrastructure has always been supported by urban planners and designers, the pandemic has served as a vital inflection point, enabling cities to pursue long-term sustainable transport initiatives, including investment in Active Travel (AT). There is an opportunity to promote AT as part of an integrated transport strategy, and to develop tools for the robust evaluation of AT impacts to inform future investment strategies. This proposal will provide our partner organisation Transport for New South Wales (with the knowledge required to achieve this.
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Prediction and control of fluid-structure interactions. Fluid-flows create a pressure that can deform the surface of a structure or cause it to vibrate; an extreme example is the fluttering of a flag. Flow-induced vibration of the external panels of vehicles causes damage, noise and can adversely affect performance. This project will develop a wholly new approach for the analysis of these interactions. The versatility and completeness of the approach permits a step-change in the design of panels ....Prediction and control of fluid-structure interactions. Fluid-flows create a pressure that can deform the surface of a structure or cause it to vibrate; an extreme example is the fluttering of a flag. Flow-induced vibration of the external panels of vehicles causes damage, noise and can adversely affect performance. This project will develop a wholly new approach for the analysis of these interactions. The versatility and completeness of the approach permits a step-change in the design of panels, reducing material and manufacturing costs without compromise to safety and performance - an immense benefit for the myriad engineered products or structures that feature flow over a deformable surface. Read moreRead less
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Combining mathematical programming and constraint programming to solve large-scale integrated scheduling problems. This project will target major savings in the airline industry, with resulting benefits for others such as tourism. The efficient use of airline fuel, which will be directly addressed in the project, is very important for the environment. The algorithms developed can improve cost and quality of service for Australian transportation, manufacturing and other industries.
The solut ....Combining mathematical programming and constraint programming to solve large-scale integrated scheduling problems. This project will target major savings in the airline industry, with resulting benefits for others such as tourism. The efficient use of airline fuel, which will be directly addressed in the project, is very important for the environment. The algorithms developed can improve cost and quality of service for Australian transportation, manufacturing and other industries.
The solutions developed within the project will be sold by the industrial partner, CTI, into major companies worldwide, and the technology will be used to develop further products.
Finally the project will extend Australia's lead in constraint programming and expertise in optimisation. This creates a major opportunity for the Australian software industry.
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From Tactical Planning to Operational Control - Bridging the Chasm. All organisations plan, and all organisations suffer from the disruptions that occur when plans are put into practice. Few organisations manage to balance operational control with planning to as to maintain both efficiency and flexibility to deal with the unexpected. This project addresses this requirement for the transportation and logistics industries.
The results discovered within the project will enable the industrial ....From Tactical Planning to Operational Control - Bridging the Chasm. All organisations plan, and all organisations suffer from the disruptions that occur when plans are put into practice. Few organisations manage to balance operational control with planning to as to maintain both efficiency and flexibility to deal with the unexpected. This project addresses this requirement for the transportation and logistics industries.
The results discovered within the project will enable the industrial partner, CTI, to develop solutions for major companies worldwide. The technology will be used to build further optimisation products.
Moreover the project will extend Australia's lead in constraint programming and expertise in optimisation. This creates a major opportunity for Australia's software industry.
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