Aggregating Data for Computational Toxicology Applications: The U.S. Environmental Protection Agency (EPA) Aggregated Computational Toxicology Resource (ACToR) System

Computational toxicology combines data from high-throughput test methods, chemical structure analyses and other biological domains (e.g., genes, proteins, cells, tissues) with the goals of predicting and understanding the underlying mechanistic causes of chemical toxicity and for predicting toxicity of new chemicals and products. A key feature of such approaches is their reliance on knowledge extracted from large collections of data and data sets in computable formats. The U.S. Environmental Protection Agency (EPA) has developed a large data resource called ACToR (Aggregated Computational Toxicology Resource) to support these data-intensive efforts. ACToR comprises four main repositories: core ACToR (chemical identifiers and structures, and summary data on hazard, exposure, use, and other domains), ToxRefDB (Toxicity Reference Database, a compilation of detailed in vivo toxicity data from guideline studies), ExpoCastDB (detailed human exposure data from observational studies of selected chemicals), and ToxCastDB (data from high-throughput screening programs, including links to underlying biological information related to genes and pathways). The EPA DSSTox (Distributed Structure-Searchable Toxicity) program provides expert-reviewed chemical structures and associated information for these and other high-interest public inventories. Overall, the ACToR system contains information on about 400,000 chemicals from 1100 different sources. The entire system is built using open source tools and is freely available to download. This review describes the organization of the data repository and provides selected examples of use cases.     

Structural and pharmacological characterization of phenylalanine-based AMPA receptor antagonists at kainate receptors

Continued efforts into the discovery of ligands that target ionotropic glutamate receptors (iGluRs) are important for studies of the physiological roles of the various iGluR subtypes as well as for the search for drugs that can be used in the treatment of diseases of the central nervous system. A new series of phenylalanine derivatives that target iGluRs was reported to bind AMPA receptors. Herein we report our studies of these compounds at the kainate receptors GluK1-3. Several compounds bind with micromolar affinity at GluK1 and GluK3, but do not bind GluK2. The crystal structure of the most potent compound in the ligand binding domain of GluK1 revealed different modes of binding to GluK1 and GluA2, due primarily to residues Ser741 (GluK1) and Met729 (GluA2). The compound was shown to be slightly more potent at GluK1 than at AMPA receptors and to induce a domain closure similar to that observed in GluK1 structures with partial agonists.     

Protocol for evaluating the efficacy of cetylpyridinium chloride as a beef hide intervention

The objective of this study was to establish the necessary protocols and assess the efficacy of cetylpyridinium chloride (CPC) as an antimicrobial intervention on beef cattle hides. Experiments using CPC were conducted to determine (i) the methods of neutralization needed to obtain valid efficacy measurements, (ii) the effect of concentration and dwell time after treatment, (iii) the effect of CPC on hide and carcass microbial populations when cattle were treated at a feedlot and then transported to a processing facility for harvest, and (iv) the effectiveness of spray pressure and two-spray combinations of CPC and water to reduce hide microbial populations. Residual CPC in hide sponge samples prevented bacterial growth. Dey-Engley neutralization media at 7.8% and a centrifugation step were necessary to overcome this problem. All dwell times, ranging from 30 s to 4 h, after 1% CPC application to cattle hides resulted in aerobic plate counts and Enterobacteriaceae counts 1.5 log CFU/100 cm2 lower than controls. The most effective dose of CPC was 1%, which reduced aerobic plate counts and Enterobacteriaceae counts 2 and 1 log CFU/100 cm2, respectively. Low-pressure application of 1% CPC at the feedlot, transport to the processing facility, and harvest within 5 h of application resulted in no effect on Escherichia coli O157 prevalence on hides or preevisceration carcasses. Two high-pressure CPC washes lowered aerobic plate counts and Enterobacteriaceae counts by 4 log CFU/100 cm2, and two medium-pressure CPC washes were only slightly less effective. These results indicate that under the proper conditions, CPC may still be effective for reducing microbial populations on cattle hides. Further study is warranted to determine if this effect will result in reduction of hide-to-carcass contamination during processing.     

Travel mode choice as a representation of travel utility: A multilevel approach reflecting the hierarchical structure of trip,individual, and neighborhood characteristics

Trip characteristics, travel utility, socio-economic characteristics, and built environment influence travel mode choice. Since the elements have a hierarchical structure, this study conducted multilevel multinomial logistic regression to evaluate the relationship between these elements and travel modes. Particularly, this study focused on how twelve types of expressed travel utilities affect travel mode choice for five travel purposes. The results show that people consider various travel utilities for each travel purpose; these elements influence the travel mode choice of cars, public transit, or non-motorized modes, for example, public transit is preferred for punctuality and multitasking in commute, and for health benefits in shopping.     

Accelerated training algorithm for feedforward neural networks based on least squares method

A least squares based training algorithm for feedforward neural networks is presented. By decomposing each neuron of the network into a linear part and a nonlinear part, the learning error can then be minimized on each neuron by applying the least squares method to solve the linear part of the neuron. In all the problems investigated, the proposed algorithm is capable of achieving the required error level in one training iteration. Comparing to the conventional backpropagation algorithm and other fast training algorithms, the proposed training algorithm provides a major breakthrough in speeding up the training process.     

Development of a more reliable version of the Matching Familiar Figures Test.

Because of the inadequate reliability of Matching Familiar Figures Test (MFFT) error scores, a longer, more reliable version was developed. As a result of item analysis of 30 MFFT-type items, 20 were selected on the basis of item—total error correlations and ability to discriminate reflective from impulsive 11-yr-old boys. Two subsequent studies with Ss of similar ages showed that split-half correlations for the new 20-item MFFT over 2 wks were .91 for latency and .89 for errors, while test–retest correlations over 5 wks were .85 and .77 for latency and errors, respectively. These results plus those of a further study with 7- and 9-yr-old boys and girls suggest that the new test (the MFF20) is suitable for use with children in the age range 7–21 yrs. (11 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Stress and water flow relation in fractured rock

Bulletin of Engineering Geology and the Environment - A field test was performed to investigate the relation between rock stresses and the hydraulic properties of a fractured rock mass. In thisin...     

Enhancing density-based data reduction using entropy

Data reduction algorithms determine a small data subset from a given large data set. In this article, new types of data reduction criteria, based on the concept of entropy, are first presented. These criteria can evaluate the data reduction performance in a sophisticated and comprehensive way. As a result, new data reduction procedures are developed. Using the newly introduced criteria, the proposed data reduction scheme is shown to be efficient and effective. In addition, an outlier-filtering strategy, which is computationally insignificant, is developed. In some instances, this strategy can substantially improve the performance of supervised data analysis. The proposed procedures are compared with related techniques in two types of application: density estimation and classification. Extensive comparative results are included to corroborate the contributions of the proposed algorithms.     

Exact Non-Reflecting Boundary Conditions on Perturbed Domains and <Emphasis Type="Italic">hp</Emphasis>-Finite Elements

For exterior scattering problems one of the chief difficulties arises from the unbounded nature of the problem domain. Inhomogeneous obstacles may require a volumetric discretization, such as the Finite Element Method (FEM), and for this approach to be feasible the exterior domain must be truncated and an appropriate condition enforced at the far, artificial, boundary. An exact, non-reflecting boundary condition can be stated using the classical DtN-FE method if the Artificial Boundary’s shape is quite specific: circular or elliptical. Recently, this approach has been generalized to permit quite general Artificial Boundaries which are shaped as perturbations of a circle resulting in the “Enhanced DtN-FE” method. In this paper we extend this method to a two-dimensional FEM featuring high-order polynomials in order to realize a high rate of convergence. This is more involved than simply specifying high-order test and trial functions as now the scatterer shape and Artificial Boundary must be faithfully represented. This entails boundary elements which conform (to high order) to the true boundary shapes. As we show, this can be accomplished and we realize an arbitrary order FEM without spurious reflections.     

Replacement of the terminal methyl group in a moth sex pheromone component by a halogen atom: Hydrophobicity and size effects on electrophysiological single-cell activities

Analogs of (Z)-5-decenyl acetate, a pheromone component of the turnip moth,Agrotis segetum, with a chloro, bromo, or iodo substituent in place of the terminal methyl group have been synthesized and tested by electrophysiological single-sensillum recordings. The electrophysiological results have been interpreted in terms of substituent size and hydrophobicity. Interaction energies based on receptor interaction models have been calculated using the molecular mechanics [MM2(85)] method. The results support our previously suggested receptor interaction model in which the terminal alkyl chain interact with a complementary hydrophobic receptor pocket with very limited flexibility.