The viscosity of bovine bone marrow was measured using samples taken from proximal and distal sites of five radii. The viscosity was found to be independent of shear rate and temperature above 37 degrees C (distal samples) and 42 degrees C (proximal samples). The viscosity of all samples fell to a lower limit of 0.04 Pas above these temperatures, irrespective of the treatments used. Below them the measured viscosity of the proximal marrow was some ten times that of the distal marrow at 35 degrees C and some 15 times that of the distal marrow at 30 degrees C. Below 30 degrees C the proximal marrow solidified. Distal marrow remained liquid to below 20 degrees C.
The complexity and size of state-of-the-art cell models have significantly increased in part due to the requirement that these models possess complex cellular functions which are thought-but not necessarily proven-to be important. Modern cell models often involve hundreds of parameters; the values of these parameters come, more often than not, from animal experiments whose relationship to the human physiology is weak with very little information on the errors in these measurements. The concomitant uncertainties in parameter values result in uncertainties in the model outputs or Quantities of Interest (QoIs). Global Sensitivity Analysis (GSA) aims at apportioning to individual parameters (or sets of parameters) their relative contribution to output uncertainty thereby introducing a measure of influence or importance of said parameters. New GSA approaches are required to deal with increased model size and complexity; a three stage methodology consisting of screening (dimension reduction), surrogate modeling, and computing Sobol' indices, is presented. The methodology is used to analyze a physiologically validated numerical model of neurovascular coupling which possess 160 uncertain parameters. The sensitivity analysis investigates three quantities of interest (QoIs), the average value of K + in the extracellular space, the average volumetric flow rate through the perfusing vessel, and the minimum value of the J.actin/myosin complex in the smooth muscle cell. GSA provides a measure of the influence of each parameter, for each of the three QoIs, giving insight into areas of possible physiological dysfunction and areas of further investigation.
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