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Figure 10 Simulation results of the ABM at 4 h post-infection for varied diffusion coefficients around the absolute least squares error (LSE) minimum with (DminG,DminM) = (425,275)  ��m2/min for (A) monocytes keeping DG fixed and (B) PMN keeping DM fixed ... In the opposite case, where DM was fixed and DG was varied between 100 ��m2/min and 600 ��m2/min, it was again observed that for increased values DG > 425 ��m2/min the impact on the immune response against C. albicans is only weak. In contrast, for decreased values DG  infection assay for  C. albicans in human blood. As illustrated in Figure ?Figure1,1, this approach combines different mathematical models with increasing complexity that build on one another. We started from a previously developed state based model (SBM), here referred to as P-SBM (H��nniger et al., 2014), that [http://www.selleckchem.com/products/otx015.html Epigenetic Reader Domain inhibitor] neglects  all spatial aspects and describes the time-evolution of pathogens in different states��e.g., alive, phagocytosed and killed��during the early response of the innate immune system. To include the immune response mediated by monocytes and granulocytes (PMN), in this work we modified the P-SBM into a SBM that does as well-explicitly account for the immune cell states and is therefore referred to as PI-SBM. The rates of state transitions in the PI-SBM were estimated by comparison with experimental data (H��nniger et al., 2014) using the global optimization method simulated annealing based on the Metropolis Monte Carlo scheme (SA-MMC). The resulting model kinetics of both SBM were found to be in quantitative agreement with experimental data and confirmed that PMN play the major role in the immune defense against C. albicans in human blood. This is indicative for the general validity of both models, despite the structural difference of the simulation algorithms regarding the level of detail at which immune cells are modeled.
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Версія за 05:42, 18 травня 2017

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