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.     

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)     

Carcinogenic polycyclic aromatic hydrocarbons increase intracellular Ca2+ and cell proliferation in primary human mammary epithelial cells

A method was developed to determine in eggs 2 components [4,6-dimethyl-2-hydroxypyrimidine and 1,3-bis(4-nitrophenyl)urea] of the anticoccidial drug nicarbazin, used to treat poultry. Samples were extracted with acetonitrile, and the extracts were washed with hexane and evaporated to dryness before analysis by liquid chromatography/mass spectrometry with atmospheric pressure chemical ionization. By switching from positive to negative ion monitoring and using gradient elution, both components were measured within one run. The limit of quantitation of the assay was 10 ng/g for each component. The results of a preliminary feeding trial in which chickens were fed contamination levels of the drug are also reported.     

Have we underestimated shiftworkers' problems? Evidence from a 'reminiscence' study

This paper argues that shiftworkers may have gradually habituated to their problems and hence that they underestimate them. Some support for this view was obtained in a 'reminiscence' questionnaire study of retired UK Police Officers who had all subsequently taken on another (mainly day-time) job. They completed a specially constructed questionnaire, which included several measures of health and well being, and in which they were asked to reminisce about how they had felt while still a shiftworker. These reminiscence scores were compared to their current perception of how they were. The results clearly indicated that individuals in retrospect perceive their situation as being worse than they realised at the time. This effect was most marked for scores on the General Health Questionnaire and Chronic Fatigue scale. The results of this study draw attention to a potential confounding in much of the shiftwork literature which demands further, more detailed, investigation.     

A quantum-well-intermixing process for wavelength-agile photonic integrated circuits

Wavelength-agile photonic integrated circuits are fabricated using a one-step ion implantation quantum-well intermixing process. In this paper, we discuss, the issues in processing optimized widely tunable multisection lasers using this technique and present the results achieved using this process. This quantum-well intermixing process is general in its application and can be used to monolithically integrate a wide variety of optoelectronic components with widely tunable lasers.     

Recovery from work shifts: How long does it take?

Although regulations on work hours usually include a minimum weekly rest period, there is little empirical evidence concerning recovery from work. Shift-working nurses (N?=?61) used a handheld computer for 28 days to complete self-ratings, cognitive-performance tasks, and a sleep diary. Many measures were worse on rest days that followed a night shift rather than a day shift and tended to be worse on 1st rest days compared with subsequent rest days. Alertness was lowest on the 1st rest day following a night shift. Social satisfaction was better on workdays that were preceded by 2 rather than 1 rest day. Reaction time (RT) decreased over consecutive night shifts and tended to increase over rest days following night shifts. The results are interpreted as being consistent with the combined adaptive costs of fatigue and adjustment to and from a nocturnal routine. The practical implications for scheduling rest days are considered. (PsycINFO Database Record (c) 2010 APA, all rights reserved)