Mathematical and computational models of drug transport in tumours

The ability to predict how far a drug will penetrate into the tumour microenvironment within its pharmacokinetic (PK) lifespan would provide valuable information about therapeutic response. As the PK profile is directly related to the route and schedule of drug administration, an in silico tool that can predict the drug administration schedule that results in optimal drug delivery to tumours would streamline clinical trial design. This paper investigates the application of mathematical and computational modelling techniques to help improve our understanding of the fundamental mechanisms underlying drug delivery, and compares the performance of a simple model with more complex approaches. Three models of drug transport are developed, all based on the same drug binding model and parametrized by bespoke in vitro experiments. Their predictions, compared for a ‘tumour cord’ geometry, are qualitatively and quantitatively similar. We assess the effect of varying the PK profile of the supplied drug, and the binding affinity of the drug to tumour cells, on the concentration of drug reaching cells and the accumulated exposure of cells to drug at arbitrary distances from a supplying blood vessel. This is a contribution towards developing a useful drug transport modelling tool for informing strategies for the treatment of tumour cells which are ‘pharmacokinetically resistant’ to chemotherapeutic strategies

Observations of Core Toroidal Rotation Reversals in Alcator C-Mod Ohmic L-mode Plasmas

Direction reversals of intrinsic toroidal rotation have been observed in Alcator C-Mod ohmic L-mode plasmas following modest electron density or toroidal magnetic field ramps. The reversal process occurs in the plasma interior, inside of the q = 3/2 surface. For low density plasmas, the rotation is in the co-current direction, and can reverse to the counter-current direction following an increase in the electron density above a certain threshold. Reversals from the co- to counter-current direction are correlated with a sharp decrease in density fluctuations with k(R) >= 2 cm(-1) and with frequencies above 70 kHz. The density at which the rotation reverses increases linearly with plasma current, and decreases with increasing magnetic field. There is a strong correlation between the reversal density and the density at which the global ohmic L-mode energy confinement changes from the linear to the saturated regime

Effects of Boson Dispersion in Fermion-Boson Coupled Systems

We study the nonlinear feedback in a fermion-boson system using an extension of dynamical mean-field theory and the quantum Monte Carlo method. In the perturbative regimes (weak-coupling and atomic limits) the effective interaction among fermions increases as the width of the boson dispersion increases. In the strong coupling regime away from the anti-adiabatic limit, the effective interaction decreases as we increase the width of the boson dispersion. This behavior is closely related with complete softening of the boson field. We elucidate the parameters that control this nonperturbative region where fluctuations of the dispersive bosons enhance the delocalization of fermions.Comment: 14 pages RevTeX including 12 PS figure

Optical excitations in a one-dimensional Mott insulator

The density-matrix renormalization-group (DMRG) method is used to investigate optical excitations in the Mott insulating phase of a one-dimensional extended Hubbard model. The linear optical conductivity is calculated using the dynamical DMRG method and the nature of the lowest optically excited states is investigated using a symmetrized DMRG approach. The numerical calculations agree perfectly with field-theoretical predictions for a small Mott gap and analytical results for a large Mott gap obtained with a strong-coupling analysis. Is is shown that four types of optical excitations exist in this Mott insulator: pairs of unbound charge excitations, excitons, excitonic strings, and charge-density-wave (CDW) droplets. Each type of excitations dominates the low-energy optical spectrum in some region of the interaction parameter space and corresponds to distinct spectral features: a continuum starting at the Mott gap (unbound charge excitations), a single peak or several isolated peaks below the Mott gap (excitons and excitonic strings, respectively), and a continuum below the Mott gap (CDW droplets).Comment: 12 pages (REVTEX 4), 12 figures (in 14 eps files), 1 tabl

Electronic dynamic Hubbard model: exact diagonalization study

A model to describe electronic correlations in energy bands is considered. The model is a generalization of the conventional Hubbard model that allows for the fact that the wavefunction for two electrons occupying the same Wannier orbital is different from the product of single electron wavefunctions. We diagonalize the Hamiltonian exactly on a four-site cluster and study its properties as function of band filling. The quasiparticle weight is found to decrease and the quasiparticle effective mass to increase as the electronic band filling increases, and spectral weight in one- and two-particle spectral functions is transfered from low to high frequencies as the band filling increases. Quasiparticles at the Fermi energy are found to be more 'dressed' when the Fermi level is in the upper half of the band (hole carriers) than when it is in the lower half of the band (electron carriers). The effective interaction between carriers is found to be strongly dependent on band filling becoming less repulsive as the band filling increases, and attractive near the top of the band in certain parameter ranges. The effective interaction is most attractive when the single hole carriers are most heavily dressed, and in the parameter regime where the effective interaction is attractive, hole carriers are found to 'undress', hence become more like electrons, when they pair. It is proposed that these are generic properties of electronic energy bands in solids that reflect a fundamental electron-hole asymmetry of condensed matter. The relation of these results to the understanding of superconductivity in solids is discussed.Comment: Small changes following referee's comment