We study the problem of globally recovering a dictionary from a set of signals via ℓ1-minimization. We assume that the signals are generated as i.i.d. random linear combinations of the K atoms from a complete reference dictionary D∗∈RK×K, where the linear combination coefficients are from either a Bernoulli type model or exact sparse model. First, we obtain a necessary and sufficient norm condition for the reference dictionary D∗ to be a sharp local minimum of the expected ℓ1 objective function. Our result substantially extends that of Wu and Yu (2015) and allows the combination coefficient to be non-negative. Secondly, we obtain an explicit bound on the region within which the objective value of the reference dictionary is minimal. Thirdly, we show that the reference dictionary is the unique sharp local minimum, thus establishing the first known global property of ℓ1-minimization dictionary learning. Motivated by the theoretical results, we introduce a perturbation based test to determine whether a dictionary is a sharp local minimum of the objective function. In addition, we also propose a new dictionary learning algorithm based on Block Coordinate Descent, called DL-BCD, which is guaranteed to decrease the obective function monotonically. Simulation studies show that DL-BCD has competitive performance in terms of recovery rate compared to other state-of-the-art dictionary learning algorithms when the reference dictionary is generated from random Gaussian matrices.

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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 skeleton of a 2D shape is an important geometric structure in pattern analysis and computer vision. In this paper we study the skeleton of a 2D shape in a two-manifold M, based on a geodesic metric. We present a formal definition of the skeleton S(\Omega) for a shape V in M and show several properties that make S(\Omega) distinct from its Euclidean counterpart in R^2. We further prove that for a shape sequence {\Omega_i} that converge to a shape V in M, the mapping \Omega\rightarrow S(\Omega_i) is lower semi-continuous. A direct application of this result is that we can use a set P of sample points to approximate the boundary of a 2D shape V in M, and the Voronoi diagram of P inside \Omega\subset M gives a good approximation to the skeleton S(\Omega). Examples of skeleton computation in topography and brain morphometry are illustrated.

The entropy solutions of the compressible Euler equations satisfy a minimum principle for the specific entropy. First order schemes such as Godunov-type and Lax-Friedrichs schemes and the second order kinetic schemes also satisfy a discrete minimum entropy principle. In this paper, we show an extension of the positivity-preserving high order schemes for the compressible Euler equations, to enforce the minimum entropy principle for high order finite volume and discontinuous Galerkin (DG) schemes.