Multiscale modeling of glioma pseudopalisades: contributions from the tumor microenvironment

Gliomas are primary brain tumors with a high invasive potential and infiltrative spread. Among them, glioblastoma multiforme (GBM) exhibits microvascular hyperplasia and pronounced necrosis triggered by hypoxia. Histological samples showing garland-like hypercellular structures (so-called pseudopalisades) centered around the occlusion site of a capillary are typical for GBM and hint on poor prognosis of patient survival. We propose a multiscale modeling approach in the kinetic theory of active particles framework and deduce by an upscaling process a reaction-diffusion model with repellent pH-taxis. We prove existence of a unique global bounded classical solution for a version of the obtained macroscopic system and investigate the asymptotic behavior of the solution. Moreover, we study two different types of scaling and compare the behavior of the obtained macroscopic PDEs by way of simulations. These show that patterns (not necessarily of Turing type), including pseudopalisades, can be formed for some parameter ranges, in accordance with the tumor grade. This is true when the PDEs are obtained via parabolic scaling (undirected tissue), while no such patterns are observed for the PDEs arising by a hyperbolic limit (directed tissue). This suggests that brain tissue might be undirected - at least as far as glioma migration is concerned. We also investigate two different ways of including cell level descriptions of response to hypoxia and the way they are related .

Intrinsic random walks in Riemannian and sub-Riemannian geometry via volume sampling

We relate some constructions of stochastic analysis to differential geometry, via random walk approximations. We consider walks on both Riemannian and sub-Riemannian manifolds in which the steps consist of travel along either geodesics or integral curves associated to orthonormal frames, and we give particular attention to walks where the choice of step is influenced by a volume on the manifold. A primary motivation is to explore how one can pass, in the parabolic scaling limit, from geodesics, orthonormal frames, and/or volumes to diffusions, and hence their infinitesimal generators, on sub-Riemannian manifolds, which is interesting in light of the fact that there is no completely canonical notion of sub-Laplacian on a general sub-Riemannian manifold. However, even in the Riemannian case, this random walk approach illuminates the geometric significance of Ito and Stratonovich stochastic differential equations as well as the role played by the volume.

Emergent parabolic scaling of nano-faceting crystal growth

Nano-faceted crystals answer the call for self-assembled, physico-chemically tailored materials, with those arising from a kinetically mediated response to free-energy disequilibria ( thermokinetics ) holding the greatest promise. The dynamics of slightly undercooled crystal–melt interfaces possessing strongly anisotropic and curvature-dependent surface energy and evolving under attachment–detachment limited kinetics offer a model system for the study of thermokinetic effects. The fundamental non-equilibrium feature of this dynamics is explicated through our discovery of one-dimensional convex and concave translating fronts ( solitons ) whose constant asymptotic angles provably deviate from the thermodynamically expected Wulff angles in direct proportion to the degree of undercooling. These thermokinetic solitons induce a novel emergent facet dynamics, which is exactly characterized via an original geometric matched-asymptotic analysis. We thereby discover an emergent parabolic symmetry of its coarsening facet ensembles, which naturally implies the universal scaling law L ∼ t 1 / 2 for the growth in time t of the characteristic length L .