Why one-size-fits-all vaso-modulatory interventions fail to control glioma invasion: in silico insights

There is an ongoing debate on the therapeutic potential of vaso-modulatory interventions against glioma invasion. Prominent vasculature-targeting therapies involve functional tumour-associated blood vessel deterioration and normalisation. The former aims at tumour infarction and nutrient deprivation medi- ated by vascular targeting agents that induce occlusion/collapse of tumour blood vessels. In contrast, the therapeutic intention of normalising the abnormal structure and function of tumour vascular net- works, e.g. via alleviating stress-induced vaso-occlusion, is to improve chemo-, immuno- and radiation therapy efficacy. Although both strategies have shown therapeutic potential, it remains unclear why they often fail to control glioma invasion into the surrounding healthy brain tissue. To shed light on this issue, we propose a mathematical model of glioma invasion focusing on the interplay between the mi- gration/proliferation dichotomy (Go-or-Grow) of glioma cells and modulations of the functional tumour vasculature. Vaso-modulatory interventions are modelled by varying the degree of vaso-occlusion. We discovered the existence of a critical cell proliferation/diffusion ratio that separates glioma invasion re- sponses to vaso-modulatory interventions into two distinct regimes. While for tumours, belonging to one regime, vascular modulations reduce the tumour front speed and increase the infiltration width, for those in the other regime the invasion speed increases and infiltration width decreases. We show how these in silico findings can be used to guide individualised approaches of vaso-modulatory treatment strategies and thereby improve success rates

The Decay Properties of the Finite Temperature Density Matrix in Metals

Using ordinary Fourier analysis, the asymptotic decay behavior of the density matrix F(r,r') is derived for the case of a metal at a finite electronic temperature. An oscillatory behavior which is damped exponentially with increasing distance between r and r' is found. The decay rate is not only determined by the electronic temperature, but also by the Fermi energy. The theoretical predictions are confirmed by numerical simulations

Total energy global optimizations using non orthogonal localized orbitals

An energy functional for orbital based $O(N)$ calculations is proposed, which depends on a number of non orthogonal, localized orbitals larger than the number of occupied states in the system, and on a parameter, the electronic chemical potential, determining the number of electrons. We show that the minimization of the functional with respect to overlapping localized orbitals can be performed so as to attain directly the ground state energy, without being trapped at local minima. The present approach overcomes the multiple minima problem present within the original formulation of orbital based $O(N)$ methods; it therefore makes it possible to perform $O(N)$ calculations for an arbitrary system, without including any information about the system bonding properties in the construction of the input wavefunctions. Furthermore, while retaining the same computational cost as the original approach, our formulation allows one to improve the variational estimate of the ground state energy, and the energy conservation during a molecular dynamics run. Several numerical examples for surfaces, bulk systems and clusters are presented and discussed.Comment: 24 pages, RevTex file, 5 figures available upon reques

Quasiparticle Electronic structure of Copper in the GW approximation

We show that the results of photoemission and inverse photoemission experiments on bulk copper can be quantitatively described within band-structure theory, with no evidence of effects beyond the single-quasiparticle approximation. The well known discrepancies between the experimental bandstructure and the Kohn-Sham eigenvalues of Density Functional Theory are almost completely corrected by self-energy effects. Exchange-correlation contributions to the self-energy arising from 3s and 3p core levels are shown to be crucial.Comment: 4 pages, 2 figures embedded in the text. 3 footnotes modified and 1 reference added. Small modifications also in the text. Accepted for publication in PR

Density-functionals not based on the electron gas: Local-density approximation for a Luttinger liquid

By shifting the reference system for the local-density approximation (LDA) from the electron gas to other model systems one obtains a new class of density functionals, which by design account for the correlations present in the chosen reference system. This strategy is illustrated by constructing an explicit LDA for the one-dimensional Hubbard model. While the traditional {\it ab initio} LDA is based on a Fermi liquid (the electron gas), this one is based on a Luttinger liquid. First applications to inhomogeneous Hubbard models, including one containing a localized impurity, are reported.Comment: 4 pages, 4 figures (final version, contains additional applications and discussion; accepted by Phys. Rev. Lett.

On the growth of the Bergman kernel near an infinite-type point

We study diagonal estimates for the Bergman kernels of certain model domains in $\mathbb{C}^2$ near boundary points that are of infinite type. To do so, we need a mild structural condition on the defining functions of interest that facilitates optimal upper and lower bounds. This is a mild condition; unlike earlier studies of this sort, we are able to make estimates for non-convex pseudoconvex domains as well. This condition quantifies, in some sense, how flat a domain is at an infinite-type boundary point. In this scheme of quantification, the model domains considered below range -- roughly speaking -- from being ``mildly infinite-type'' to very flat at the infinite-type points.Comment: Significant revisions made; simpler estimates; very mild strengthening of the hypotheses on Theorem 1.2 to get much stronger conclusions than in ver.1. To appear in Math. An

Statistical mechanics of Floquet systems: the pervasive problem of near degeneracies

The statistical mechanics of periodically driven ("Floquet") systems in contact with a heat bath exhibits some radical differences from the traditional statistical mechanics of undriven systems. In Floquet systems all quasienergies can be placed in a finite frequency interval, and the number of near degeneracies in this interval grows without limit as the dimension N of the Hilbert space increases. This leads to pathologies, including drastic changes in the Floquet states, as N increases. In earlier work these difficulties were put aside by fixing N, while taking the coupling to the bath to be smaller than any quasienergy difference. This led to a simple explicit theory for the reduced density matrix, but with some major differences from the usual time independent statistical mechanics. We show that, for weak but finite coupling between system and heat bath, the accuracy of a calculation within the truncated Hilbert space spanned by the N lowest energy eigenstates of the undriven system is limited, as N increases indefinitely, only by the usual neglect of bath memory effects within the Born and Markov approximations. As we seek higher accuracy by increasing N, we inevitably encounter quasienergy differences smaller than the system-bath coupling. We therefore derive the steady state reduced density matrix without restriction on the size of quasienergy splittings. In general, it is no longer diagonal in the Floquet states. We analyze, in particular, the behavior near a weakly avoided crossing, where quasienergy near degeneracies routinely appear. The explicit form of our results for the denisty matrix gives a consistent prescription for the statistical mechanics for many periodically driven systems with N infinite, in spite of the Floquet state pathologies.Comment: 31 pages, 3 figure

Van der Waals forces in density functional theory: perturbational long-range electron interaction corrections

Long-range exchange and correlation effects, responsible for the failure of currently used approximate density functionals in describing van der Waals forces, are taken into account explicitly after a separation of the electron-electron interaction in the Hamiltonian into short- and long-range components. We propose a "range-separated hybrid" functional based on a local density approximation for the short-range exchange-correlation energy, combined with a long-range exact exchange energy. Long-range correlation effects are added by a second-order perturbational treatment. The resulting scheme is general and is particularly well-adapted to describe van der Waals complexes, like rare gas dimers.Comment: 8 pages, 1 figure, submitted to Phys. Rev.

Exact-exchange density-functional theory for quasi-two-dimensional electron gases

A simple exact-exchange density-functional method for a quasi-two-dimensional electron gas with variable density is presented. An analytical expression for the exact-exchange potential with only one occupied subband is provided, without approximations. When more subbands are occupied the exact-exchange potential is obtained numerically. The theory shows that, in contradiction with LDA, the exact-exchange potential exhibits discontinuities and the system suffers a zero-temperature first-order transition each time a subband is occupied. Results suggesting that the translational symmetry might be spontaneously broken at zero temperature are presented. An extension of the theory to finite temperatures allows to describe a drop in the intersubband spacing in good quantitative agreement with recent experiments.Comment: 14 pages, 3 figure