Continuing development of a computer system (SAAM) for the simulation, analysis, and modeling of bio-kinetic systems. Development of a library of benchmark problems were extended to include examples which can be used to verify the implementation of newer integration methodology into the program. Performance studies with SAAM and CONSAM on the MicroVAX-II indicates that the MicroVAX has about 80% of the performance of the VAX 11/780 for a single user and that system performance while running SAAM and CONSAM is highly dependent on disk space management, the neglect of which can result in a 15 fold degradation in performance. Further development of SAAM/CONSAM resulted in the development of version 29 which will handle 3 times the number of data points. Starting with a uniform method for testing local identifiability we have shown that an implicit function approach provides a common basis for examining local identifiability and estimability. These results lead towards a practical solution of the optimal sampling problem. The local identifiability based on linearization around initial parameter estimates has led to the examination of the information contained in the a priori correlation matrix, which is the correlation generated in the identifiability stage from error free generated data. Estimability has been posed as a measure of the independence of locally identifiable parameters when examined as the a priori correlation coefficients. In vivo transport of free cholesterol and esterified cholesterol among the components of blood was investigated resulting in: erythrocyte FC conformed to a single pool which exchanged in a bidirectional fashion with both HDL and LDL/VLDL without evidence of net FC transport. The plasma concentration of HDL-FC was less than 30% of LDL/VLDL-FC but erythrocyte FC exchange with HDL substantially exceeded that with LDL/VLDL (10 vs. 4.4 umolzz/min respectively). The finding that HDL mediates extensive FC exchange between plasma and tissue without transfer of EC to tissue indicates a unique mechanism of HDL-plasma membrane interaction.
