Computing and Information Systems - Research Publications
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ItemNo Preview AvailableDiscrete network models of interacting nephrons(ELSEVIER SCIENCE BV, 2009-11-15)The kidney is one of the major organs involved in whole-body homeostasis, and aexhibits many of the properties of a complex system. The functional unit of the kidney is the nephron, a complex, segmented tube into which blood plasma is filtered and its composition adjusted. Although the behaviour of individual nephrons can fluctuate widely and even chaotically, the behaviour of the kidney remains stable. In this paper, we investigate how the filtration rate of a multi-nephron system is affected by interactions between nephrons. We introduce a discrete-time multi-nephron network model. The tubular mechanisms that have the greatest effect on filtration rate are the transport of sodium and water, consequently our model attempts to capture these mechanisms. Multi-nephron systems also incorporate two competing coupling mechanisms-vascular and hemodynamic-that enforce in-phase and anti-phase synchronisations respectively. Using a two-nephron model, we demonstrate how changing the strength of the hemodynamic coupling mechanism and changing the arterial blood pressure have equivalent effects on the system. The same two-nephron system is then used to demonstrate the interactions that arise between the two coupling mechanisms. We conclude by arguing that our approach is scalable to large numbers of nephrons, based on the performance characteristics of the model.
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ItemNo Preview AvailableA computational model for emergent dynamics in the kidney(ROYAL SOC, 2009-06-13)In this paper, concepts from network automata are adapted and extended to model complex biological systems. Specifically, systems of nephrons, the operational units of the kidney, are modelled and the dynamics of such systems are explored. Nephron behaviour can fluctuate widely and, under certain conditions, become chaotic. However, the behaviour of the whole kidney remains remarkably stable and blood solute levels are maintained under a wide range of conditions even when many nephrons are damaged or lost. A network model is used to investigate the stability of systems of nephrons and interactions between nephrons. More sophisticated dynamics are explored including the observed oscillations in single nephron filtration rates and the development of stable ionic and osmotic gradients in the inner medulla which contribute to the countercurrent exchange mechanism. We have used the model to explore the effects of changes in input parameters including hydrostatic and osmotic pressures and concentrations of ions, such as sodium and chloride. The intrinsic nephron control, tubuloglomerular feedback, is included and the effects of coupling between nephrons are explored in two-, eight- and 72-nephron models.
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ItemThe Virtual Kidney: an eScience interface and Grid portal(ROYAL SOC, 2009-06-13)The Virtual Kidney uses a web interface and distributed computing to provide experimental scientists and analysts with access to computational simulations and knowledge databases hosted in geographically separated laboratories. Users can explore a variety of complex models without requiring the specific programming environment in which applications have been developed. This initiative exploits high-bandwidth communication networks for collaborative research and for shared access to knowledge resources. The Virtual Kidney has been developed within a specialist community of renal scientists but is transferable to other areas of research requiring interaction between published literature and databases, theoretical models and simulations and the formulation of effective experimental designs. A web-based three-dimensional interface provides access to experimental data, a parameter database and mathematical models. A multi-scale kidney reconstruction includes blood vessels and serially sectioned nephrons. Selection of structures provides links to the database, returning parameter values and extracts from the literature. Models are run locally or remotely with a Grid resource broker managing scheduling, monitoring and visualization of simulation results and application, credential and resource allocation. Simulation results are viewed graphically or as scaled colour gradients on the Virtual Kidney structures, allowing visual and quantitative appreciation of the effects of simulated parameter changes.