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By Trachette Jackson, Ami Radunskaya

This quantity highlights difficulties from a number organic and clinical purposes that may be interpreted as questions on procedure habit or regulate. subject matters contain drug resistance in melanoma and malaria, organic fluid dynamics, auto-regulation within the kidney, anti-coagulation treatment, evolutionary diversification and photo-transduction. Mathematical recommendations used to explain and examine those organic and clinical difficulties comprise traditional, partial and stochastic differentiation equations, hybrid discrete-continuous methods, in addition to 2 and 3D numerical simulation.

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The result is a colony of a few surviving hypoxic cells descended from the parent cells initially placed in the low drug niches. When Δdeath is at a higher value, the microenvironmental niche also determines which cells survive. In this case, however, the surviving cells actually result in treatment failure. The tumor that eventually takes over tissue space lacks clonal diversity. The selective powers of the microenvironmental niche are highlighted in FIG. 1g. The first period of selection occurs after a clonally heterogeneous tumor starts to overtake tissue space.

Sufficiently small, the microenvironmental niche influences which cells survive the longest, though all cells will eventually die. Cells originally located near the lowdrug/normoxic niche initially accumulate damage at a much slower rate than their neighbors while still increasing their death threshold. 1). 2. This behavior is driven by the microenvironmental niche. Cells initially placed near the low-drug/normoxic niche are selected for, and the increase in Δdeath lends them the time needed to reproduce enough to move the tumor mass toward the hypoxic region.

Appendix Before testing various mechanisms of tumor resistance, our model has been calibrated to 1) achieve a stable gradient of oxygen when no cancer cells are present, as would be the case in healthy tissue; 2) generate a tumor cluster that completely fills the available space when no drug is applied as would take place in non-treated tumors; this will result in another stable gradient of oxygen with hypoxic areas located far from the vasculature; and 3) completely eliminate the tumor during the treatment when the cells do not acquire resistance.

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