Prediction of Chameleonic Efficiency

Chameleonic properties, i. e., the capacity of a molecule to hide polarity in non-polar environments and expose it in water, help achieving sufficient permeability and solubility for drug molecules with high MW. We present models of experimental measures of polarity for a set of 24 FDA approved drugs (MW 405-1113) and one PROTAC (MW 1034). Conformational ensembles in aqueous and non-polar environments were generated using molecular dynamics. A linear regression model that predicts chromatographic apparent polarity (EPSA) with a mean unsigned error of 10 Ų was derived based on separate terms for donor, acceptor, and total molecular SASA. A good correlation (R²=0.92) with an experimental measure of hydrogen bond donor potential, Δlog P_oct-tol, was found for the mean hydrogen bond donor SASA of the conformational ensemble scaled with Abraham's A hydrogen bond acidity. Two quantitative measures of chameleonic behaviour, the chameleonic efficiency indices, are introduced. We envision that the methods presented herein will be useful to triage designed molecules and prioritize those with the best chance of achieving acceptable permeability and solubility.     

On upgrading the numerics in combustion chemistry codes

A method of updating and reusing legacy FORTRAN codes for combustion simulations is presented using the DAEPACK software package. The procedure is demonstrated on two codes that come with the CHEMKIN-II package, CONP and SENKIN, for the constant-pressure batch reactor simulation. Using DAEPACK generated code, analytical derivative calculations, sparsity pattern information, and hidden discontinuity information can be obtained for the models of interest. This information can be easily integrated with different solvers giving the modeler great flexibility in selecting the best solution procedure. Using the generated code, the CONP code was connected to three different solvers, and the SENKIN code was connected to two different solvers. The effect of model formulation, analytical derivatives, sparsity, and sensitivity equation solution method were analyzed for three large kinetic mechanisms for methane, acetylene, and n-heptane. For the n-heptane model, with 544 species and 2446 reactions, a factor of 10-speed improvement over the original solution procedure was found using analytical derivatives and sparse linear algebra. For sensitivity calculations, for a small number of parameters, a factor of 55 improvement over the original solution procedure was found for the n-heptane problem. Upon closer examination of results, no one method is found to always be superior to other methods, and selection of the appropriate solution procedure requires an examination of the specific kinetic mechanism, which is easily conducted using DAEPACK generated code.     

Simulation of the submerged energy nozzle-mold water model system using laser-optical and computational fluid dynamics methods

The present work describes quantitative digital particle image velocimetry measurements of a full-scale water model of a thin slab mold. Different casting speeds and two submerged entry nozzles with one and two outlet ports have been investigated. The flow pattern of the single-port nozzle shows a counterclockwise-rotating double vortex that is nearly steady-state but leads to high stationary surface waves. The flow jets out of the two-port nozzle oscillate and produce a transient flow pattern with low wave amplitudes. The amplitudes for the one-port nozzle show a linear variation with the volumetric flow rate. The experimental results lead to a good interpretation of the flow phenomena and are used to validate steady-state numerical simulations with the commercial program, CFX, on the basis of the Reynolds equations. To describe anisotropic turbulence effects, the Reynolds stress model (RSM) is used for the flat single-port nozzle and the standard k-ɛ model for the mold flow. The calculated mean velocities and wave amplitudes, predicted from pressure distribution at the water surface, are generally in the consensus of the experimental data. An erratum to this article is available at .     

The role of occlusion in the perception of depth, lightness, and opacity.

A theory is presented that explains how the visual system infers the lightness, opacity, and depth of surfaces from stereoscopic images. It is shown that the polarity and magnitude of image contrast play distinct roles in surface perception, which can be captured by 2 principles of perceptual inference. First, a contrast depth asymmetry principle articulates how the visual system computes the ordinal depth and lightness relationships from the polarity of local, binocularly matched image contrast. Second, a global transmittance anchoring principle expresses how variations in contrast magnitudes are used to infer the presence of transparent surfaces. It is argued that these principles provide a unified explanation of how the visual system computes the 3-D surface structure of opaque and transparent surfaces. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Three-dimensional MHD high-resolution computations with CWENO employing adaptive mesh refinement

Until recently, numerical simulations of discontinuities in highly super-Alfvénic plasmas have been severely limited by comparatively crude resolution and accuracy. Significant progress in the numerical simulation of such plasmas was achieved with the recently implemented Central Weighted Essentially Non-Oscillatory (CWENO) scheme. Combining this technique with that of adaptive mesh refinement (AMR), we have developed a third-order numerical scheme, which is able to efficiently capture strong gradients on spatial scales being small compared to the overall scale of the plasma system considered. Here, we first describe important algorithmic aspects of the scheme as well as the physics included in it. Second, we present the results of various performance tests. And, third, we illustrate its application to ‘real world problems’ using the example of the dynamics of a Sedov-type explosion.