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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Quantitative structure-activity relationship (QSAR) modelers often encounter the problem of multicollinearity owing to the availability of large numbers of computable molecular descriptors. Sparsity of the variables while using descriptors such as atom pairs increases the complexity. Three different predictor-thinning methods, namely, a modified Gram-Schmidt algorithm, a marginal soft thresholding algorithm, and LASSO (least absolute shrinkage and selection operator), were utilized to reduce the number of descriptors prior to developing linear models. Juvenile hormone (JH) activity of 304 compounds on Culex pipiens larvae was taken as the model data set, and predictor trimming of a large number of diverse descriptors comprising 268 global molecular descriptors (topostructural, topochemical, and geometrical), 13 quantum chemical descriptors, and 915 atom pairs (substructural counts) was applied prior to linear regression by the ridge regression method. The data set (N = 304) was split into five calibration data sets of random samples of sizes 60/110/160/210/260, and the remaining 244/194/144/94/44 compounds were used for validations. LASSO was not found to be a very effective method in handling a large set of descriptors because the number of predictors retained could not exceed the number of observations. The results indicated that the modified Gram-Schmidt algorithm could be used to trim the number of predictors in the global molecular descriptor set where collinearity of the descriptors was the major concern. On the contrary, the soft thresholding approach was found to be an effective tool in subset selection from a diverse set of descriptors having both sparsity and multicollinearity, as in the case of the combined set of atom pairs and global molecular descriptors. The final model developed after variable selection was dominated more by atom pairs, which indicated the important structural moieties that affect JH activity of the compounds. The success of the method reiterates the fact that QSAR or quantitative structure-property relationship (QSPR) models can be developed for a diverse set of compounds using properly parametrized and diverse sets of descriptors, of course, with the selection of the appropriate statistical tools.
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PMID:Quantitative structure-activity relationship modeling of juvenile hormone mimetic compounds for Culex pipiens larvae, with a discussion of descriptor-thinning methods. 1642 41

Quantitative structure-activity relationship (QSAR) models were developed for the prediction of dermal absorption based on experimental log Kp data for a diverse set of 101 chemicals obtained from the literature. Molecular descriptors including topostructural (TS), topochemical (TC), shape or three-dimensional (3D) and quantum chemical (QC) indices were calculated. Based on this information, a generic predictive model was created using the diverse set of 101 compounds. In addition, two submodels were prepared for subsets of 79 cyclic and 22 acyclic chemicals. A modified Gram-Schmidt variable reduction algorithm for descriptor thinning was followed by regression analyses using ridge regression (RR), principal components regression (PCR) and partial least squares regression (PLS). The RR results were found to be superior to PLS and PCR regressions. The cross-validated correlation coefficients for the full set and subsets were 0.67-0.87. Computational methods such as QSAR modelling can be used to augment existing data to prioritise chemicals that need to be studied further for toxicological evaluation and risk assessment.
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PMID:A quantitative structure-activity relationship (QSAR) study of dermal absorption using theoretical molecular descriptors. 1736 58

The fundamental study of blood flow past a circular cylinder filled with an oxygen source is investigated as a building block for an artificial lung. The Casson constitutive equation is used to describe the shear-thinning and yield stress properties of blood. The presence of hemoglobin is also considered. Far from the cylinder, a pulsatile blood flow in the x direction is prescribed, represented by a time periodic (sinusoidal) component superimposed on a steady velocity. The dimensionless parameters of interest for the characterization of the flow and transport are the steady Reynolds number (Re), Womersley parameter (alpha), pulsation amplitude (A), and the Schmidt number (Sc). The Hill equation is used to describe the saturation curve of hemoglobin with oxygen. Two different feed-gas mixtures were considered: pure O(2) and air. The flow and concentration fields were computed for Re=5, 10, and 40, 0< or =A< or =0.75, alpha=0.25, 0.4, and Schmidt number, Sc=1000. The Casson fluid properties result in reduced recirculations (when present) downstream of the cylinder as compared to a Newtonian fluid. These vortices oscillate in size and strength as A and alpha are varied. Hemoglobin enhances mass transport and is especially important for an air feed which is dominated by oxyhemoglobin dispersion near the cylinder. For a pure O(2) feed, oxygen transport in the plasma dominates near the cylinder. Maximum oxygen transport is achieved by operating near steady flow (small A) for both feed-gas mixtures. The time averaged Sherwood number, Sh, is found to be largely influenced by the steady Reynolds number, increasing as Re increases and decreasing with A. Little change is observed with varying alpha for the ranges investigated. The effect of pulsatility on Sh is greater at larger Re. Increasing Re aids transport, but yields a higher cylinder drag force and shear stresses on the cylinder surface which are potentially undesirable.
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PMID:Pulsatile blood flow and oxygen transport past a circular cylinder. 1740 25

Using the inverted phase-contrast microscope, the living undamaged frog sciatic nerve fibers and the fibers mechanically injured to varying degrees, were studied. It was found that the swelling of myelin incisures (MI) (of Schmidt-Lanterman) occured according to the principles similar to those controlling the changes of the myelin gap (node of Ranvier) and depended on the swelling of a Schwann cell (SC) perikaryon. It was detected that this was a single process, which which could be united in a complex of nonspecific changes of a myelinated nerve fiber. It was also demonstrated that under the action of mechanical injury and hypotonic solution, swelling of MI, nodes of Ranvier and SC perikaryon occurred without modifications of outer fiber diameter, due to the pronounced local axon thinning. Electron microscopic study of the cytoskeletal axonal structures showed that there was not a simple local contraction of an axon, but a significant local increase in the density of cytoskeletal components of the axoplasm (by 200-275%). Reactive reversible remodeling of a myelinated fiber suggests a new type of interaction between the axon and SC, the mechanism of reversible translocation of liquid axoplasmic fraction to the glial cell cytoplasm.
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PMID:[Interdependent changes of the axon and Schwann cell in the process of reactive remodeling of a myelinated nerve fiber]. 2389 20

Autoimmune polyendocrine syndrome type II (APS II) is a rare endocrine disorder that involves the adrenal gland (Addison's disease), thyroid (autoimmune thyroiditis), pancreas (type 1 diabetes), and other non-endocrine organs. Herein, we report a case of a 58-year-old woman with a past medical history of systemic lupus erythematosus (SLE) and Addison's disease, who initially presented with nocturia, polyuria, abnormal sweating, fatigue, hair thinning, heat and cold intolerance, and progressive darkening of the skin for the last few months. After a thorough evaluation, she was diagnosed with autoimmune thyroiditis, and thus, she met the criteria for APS II. This report highlights the unusual presentation of APS II in a patient with SLE. We also discuss common pathophysiological mechanisms that can explain the concurrence of SLE and APS II in this patient.
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PMID:Co-Occurrence of Systemic Lupus Erythematosus and Autoimmune Polyendocrine Syndrome II: Is There a Pathologic Link? 3326 18