We consider an inverse time-dependent source problem governed by a distributed time-fractional diffusion equation using interior measurement data. Such a problem arises in some ultra-slowdiffusion phenomena in many applied areas. Based on the regularity result of the solution to the direct problem, we establish the solvability of this inverse problem as well as the conditional stability in suitable function space with a weak norm. By a variational identity connecting the unknown time-dependent source and the interior measurement data, the conjugate gradient method is also introduced to construct the inversion algorithm under the framework of regularizing scheme. We show the validity of the proposed scheme by several numerical examples.

Ligand-receptor binding and unbinding are fundamental biomolecular processes and particularly essential to drug efficacy. Environmental water fluctuations, however, impact the corresponding thermodynamics and kinetics and thereby challenge theoretical descriptions. Here, we devise a holistic, implicit-solvent, multi-method approach to predict the (un)binding kinetics for a generic ligand-pocket model. We use the variational implicit-solvent model (VISM) to calculate the solute-solvent interfacial structures and the corresponding free energies, and combine the VISM with the string method to obtain the minimum energy paths and transition states between the various metastable (“dry” and “wet”) hydration states. The resulting dry-wet transition rates are then used in a spatially-dependent multi-state continuous-time Markov chain Brownian dynamics simulations, and the related Fokker–Planck equation calculations, of the ligand stochastic motion, providing the mean first-passage times for binding and unbinding. We find the hydration transitions to significantly slow down the binding process, in semi-quantitative agreement with existing explicit-water simulations, but significantly accelerate the unbinding process. Moreover, our methods allow the characterization of non-equilibrium hydration states of pocket and ligand during the ligand movement, for which we find substantial memory and hysteresis effects for binding versus unbinding. Our study thus provides a significant step forward towards efficient, physics-based interpretation and predictions of the complex kinetics in realistic ligand-receptor systems.

The main purpose of this paper is to give stability analysis and error estimates of the local discontinuous Galerkin (LDG) methods coupled with three specific implicit-explicit (IMEX) Runge-Kutta time discretization methods up to third order accuracy, for solving one-dimensional time-dependent linear fourth order partial differential equations. In the time discretization, all the lower order derivative terms are treated explicitly and the fourth order derivative term is treated implicitly. By the aid of energy analysis, we show that the IMEX-LDG schemes are unconditionally energy stable, in the sense that the time step $\dt$ is only required to be upper-bounded by a constant which is independent of the mesh size $h$. The optimal error estimate is also derived by the aid of the elliptic projection and the adjoint argument. Numerical experiments are given to verify that the corresponding IMEX-LDG schemes can achieve optimal error accuracy.

Eigenvectors and eigenvalues of discrete Laplacians are often used for manifold learning and nonlinear dimensionality reduction. Graph Laplacian is one widely used discrete laplacian on point cloud. It was previously proved by Belkin and Niyogi [4] that the eigenvectors and eigenvalues of the graph Laplacian converge to the eigenfunctions and eigenvalues of the Laplace-Beltrami operator of the manifold in the limit of innitely many data points sampled independently from the uniform distribution over the manifold. Recently, we introduced Point Integral method (PIM) [15] to solve elliptic equations and corresponding eigenvalue problem on point clouds. In this paper, we prove that the eigenvectors and eigenvalues obtained by PIM converge in the limit of innitely many random samples. Moreover, one estimate of the rate of the convergence is given.

BDDC (Balancing Domain Decomposition by Constraints) and FETI-DP (Dual-Primal Finite Element Tearing and Interconnecting) algorithms with adaptively enriched coarse spaces are developed and analyzed for second order elliptic problems with high contrast and random coefficients. Among many approaches to form adaptive coarse spaces, we consider an approach using eigenvectors of generalized eigenvalues problems defined on each subdomain interface, seeMandel and Sousedk(2007), Galvis and Efendiev(2010), Spillane etal.(2011), Spillane etal.(2013), Klawonn etal.(2015).