Asymptotic and numerical results for a model of solvent-dependent drug diffusion through polymeric spheres

A model for drug diffusion from a spherical polymeric drug delivery device is considered. The model contains two key features. The first is that solvent diffuses into the polymer, which then transitions from a glassy to a rubbery state. The interface between the two states of polymer is modelled as a moving boundary, whose speed is governed by a kinetic law; the same moving boundary problem arises in the one-phase limit of a Stefan problem with kinetic undercooling. The second feature is that drug diffuses only through the rubbery region, with a nonlinear diffusion coefficient that depends on the concentration of solvent. We analyse the model using both formal asymptotics and numerical computation, the latter by applying a front-fixing scheme with a finite volume method. Previous results are extended and comparisons are made with linear models that work well under certain parameter regimes. Finally, a model for a multi-layered drug delivery device is suggested, which allows for more flexible control of drug release.

Natural convection flow with combined buoyancy effects due to thermal and mass diffusion in a thermally stratified media

We present here a numerical study of laminar doubly diffusive free convection flows adjacent to a vertical surface in a stable thermally stratified medium. The governing equations of mass, momentum, energy and species are non-dimensionalized. These equations have been solved by using an implicit finite difference method and local non-similarity method. The results show many interesting aspects of complex interaction of the two buoyant mechanisms that have been shown in both the tabular as well as graphical form.

Homodimerization controls the fibroblast growth factor 9 subfamily's receptor binding and heparan sulfate-dependent diffusion in the extracellular matrix

Uncontrolled fibroblast growth factor (FGF) signaling can lead to human diseases, necessitating multiple layers of self-regulatory control mechanisms to keep its activity in check. Herein, we demonstrate that FGF9 and FGF20 ligands undergo a reversible homodimerization, occluding their key receptor binding sites. To test the role of dimerization in ligand autoinhibition, we introduced structure-based mutations into the dimer interfaces of FGF9 and FGF20. The mutations weakened the ability of the ligands to dimerize, effectively increasing the concentrations of monomeric ligands capable of binding and activating their cognate FGF receptor in vitro and in living cells. Interestingly, the monomeric ligands exhibit reduced heparin binding, resulting in their increased radii of heparan sulfate-dependent diffusion and biologic action, as evidenced by the wider dilation area of ex vivo lung cultures in response to implanted mutant FGF9-loaded beads. Hence, our data demonstrate that homodimerization autoregulates FGF9 and FGF20's receptor binding and concentration gradients in the extracellular matrix. Our study is the first to implicate ligand dimerization as an autoregulatory mechanism for growth factor bioactivity and sets the stage for engineering modified FGF9 subfamily ligands, with desired activity for use in both basic and translational research.

An implicit RBF meshless approach for time fractional diffusion equations

This paper aims to develop an implicit meshless approach based on the radial basis function (RBF) for numerical simulation of time fractional diffusion equations. The meshless RBF interpolation is firstly briefed. The discrete equations for two-dimensional time fractional diffusion equation (FDE) are obtained by using the meshless RBF shape functions and the strong-forms of the time FDE. The stability and convergence of this meshless approach are discussed and theoretically proven. Numerical examples with different problem domains and different nodal distributions are studied to validate and investigate accuracy and efficiency of the newly developed meshless approach. It has proven that the present meshless formulation is very effective for modeling and simulation of fractional differential equations.

Fiduciary Duty and the Atmospheric Trust

This book explores the application of concepts of fiduciary duty or public trust in responding to the policy and governance challenges posed by policy problems that extend over multiple terms of government or even, as in the case of climate change, human generations. The volume brings together a range of perspectives including leading international thinkers on questions of fiduciary duty and public trust, Australia's most prominent judicial advocate for the application of fiduciary duty, top law scholars from several major universities, expert commentary from an influential climate policy think-tank and the views of long-serving highly respected past and present parliamentarians. The book presents a detailed examination of the nature and extent of fiduciary duty, looking at the example of Australia and having regard to developments in comparable jurisdictions. It identifies principles that could improve the accountability of political actors for their responses to major problems that may extend over multiple electoral cycles.

Novel numerical methods for time-space fractional reaction diffusion equations in two dimensions

We consider time-space fractional reaction diffusion equations in two dimensions. This equation is obtained from the standard reaction diffusion equation by replacing the first order time derivative with the Caputo fractional derivative, and the second order space derivatives with the fractional Laplacian. Using the matrix transfer technique proposed by Ilic, Liu, Turner and Anh [Fract. Calc. Appl. Anal., 9:333--349, 2006] and the numerical solution strategy used by Yang, Turner, Liu, and Ilic [SIAM J. Scientific Computing, 33:1159--1180, 2011], the solution of the time-space fractional reaction diffusion equations in two dimensions can be written in terms of a matrix function vector product $f(A)b$ at each time step, where $A$ is an approximate matrix representation of the standard Laplacian. We use the finite volume method over unstructured triangular meshes to generate the matrix $A$, which is therefore non-symmetric. However, the standard Lanczos method for approximating $f(A)b$ requires that $A$ is symmetric. We propose a simple and novel transformation in which the standard Lanczos method is still applicable to find $f(A)b$, despite the loss of symmetry. Numerical results are presented to verify the accuracy and efficiency of our newly proposed numerical solution strategy.

An analytical solution for diffusion and nonlinear uptake of oxygen in a spherical cell

We develop a new analytical solution for a reactive transport model that describes the steady-state distribution of oxygen subject to diffusive transport and nonlinear uptake in a sphere. This model was originally reported by Lin (Journal of Theoretical Biology, 1976 v60, pp449–457) to represent the distribution of oxygen inside a cell and has since been studied extensively by both the numerical analysis and formal analysis communities. Here we extend these previous studies by deriving an analytical solution to a generalized reaction-diffusion equation that encompasses Lin’s model as a particular case. We evaluate the solution for the parameter combinations presented by Lin and show that the new solutions are identical to a grid-independent numerical approximation.