This proposal seeks funds for the acquisition of a 64-bit array processor to be used in conjunction with an existing 32-bit minicomputer. Projects in four subject areas will benefit from access to such a high speed computational capability. The four projects are: 1) a simulation of the urinary concentrating mechanism in the renal medulla. Previous simulations have fallen short of predicting the performance achieved by laboratory animals; this project seeks to improve performance by incorporating known membrane transport parameters into a more realistic model of medullary anatomy. The simulation will require the solution of a large non-linear boundary value problem. 2a) a syntactic model of glycogen metabolism in liver and muscle. Compartment models based on radioactive tracer data have failed to deal with recycling of tracer molecules, and also with the difficulty of predicting the incorporation of tracer into glycogen, a large polysaccharide molecule with a preferred order of glucose incorporation and removal. Syntactic modelling keeps track of each carbon atom in each molecule as it progresses through the metabolic pathways. 2b) A minimal model of body glucose and insulin dynamics has been used in human beings to aid in the early diagnosis of diabetes mellitus; the method depends on measuring the response to a standard forcing by injecting glucose. The success of the approach now requires the design of optimal strategies for both injection and sampling protocols. 3) The Na-K-ATPase is an ubiquitous transport enzyme which has come to occupy a central place in most schemes of cellular electrolyte transport and cell volume regulation. Complete amino acid sequence information is available for this protein, but understanding the mechanism of transport and of energy transduction requires the determination of secondary and tertiary protein structure. An attempt will be made to simulate these structures from the known sequences. 4) Experimental evidence suggests that the semicircular canal cupula of the vestibular apparatus in the guitarfish acts as a pressure sensitive membrane with site specific response characteristics related to the dynamics of the stimulus. This hypothesis can be evaluated by a finite element analysis that includes temporally as well as spatially dependent variables.
