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.     

The association of gonorrhoea and syphilis with premature birth and low birthweight

The indications and results of single and double lung transplantation are described on the basis of 66 operations performed by the authors and on the background of the world literature. Lung transplantation is considered a new and promising therapeutic mode for treating patients with end-stage pulmonary failure related to fibrosis, emphysema, infective conditions, and pulmonary hypertension yielding satisfactory early results. The long-term prognosis of patients undergoing lung transplantation, like that of any other organ transfer, remains guarded.     

Cytokine profiles of stimulated blood lymphocytes in asthmatic and healthy adolescents across the school year

T cell cytokines play an important role in mediating airway inflammation in asthma. The predominance of a Th2 cytokine profile, particularly interleukin (IL)-4 and IL-5, is associated with the pathogenesis and course of asthma. The aim of this study was to test the hypothesis that a stressful life event alters the pattern of cytokine release in asthmatic individuals. Thirteen healthy controls and 21 asthmatic adolescents gave blood samples three times over a semester: midsemester, during the week of final examinations, and 2-3 weeks after examinations. Interferon-gamma (IFN-gamma), IL-2, IL-4, and IL-5 were measured from supernatants of cells stimulated with PHA/PMA for 24 h. Cells from asthmatic subjects released significantly more IL-5 during the examination and postexamination periods, whereas cells from healthy controls released significantly more IL-2 during the midsemester and examination periods, thereby indicating a bias for a Th2-like pattern in asthmatics and a Th1-like pattern in healthy controls. IL-4 and IL-5 production showed a marked decrease during and after examinations in healthy controls, whereas this decline was absent in asthmatics. The ratios of IFN-gamma:IL-4 and IFN-gamma:IL-5 also revealed significant changes in the profile of cytokine release across the semester. These results indicate differential cytokine responses in asthmatics that may become pronounced during periods of cellular activation.     

Absence of detectable human herpesvirus 8 in the semen of human immunodeficiency virus-infected men without Kaposi's sarcoma

The prevalence of human herpesvirus 8 (HHV-8)/Kaposi's sarcoma (KS)-associated herpesvirus was investigated in the semen of 99 human immunodeficiency virus (HIV)-infected men (median CD4 cell count, 357/mm3) by use of a polymerase chain reaction (PCR) assay capable of detecting <10 copies of HHV-8 DNA. Of the subjects, 95 (96%) self-identified as men who have sex with men (MSM), and 3 had a history of clinical KS. Seminal cell specimens were negative for HHV-8 in 98 subjects. None of the 26 without KS (27.1% of 96 tested) who were seropositive for HHV-8 by IFA for latency-associated nuclear antigens had HHV-8 detected in their semen. The only subject with any evidence for seminal HHV-8 DNA was seropositive for HHV-8 and had active KS. HHV-8 was detected in 10 (10.4%) of 96 peripheral blood mononuclear cell specimens. The prevalence of HHV-8 DNA by PCR in semen of HIV-infected MSM without KS is low.     

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)