BLASTing small molecules—statistics and extreme statistics of chemical similarity scores

Motivation: Small organic molecules, from nucleotides and amino acids to metabolites and drugs, play a fundamental role in chemistry, biology and medicine. As databases of small molecules continue to grow and become more open, it is important to develop the tools to search them efficiently. In order to develop a BLAST-like tool for small molecules, one must first understand the statistical behavior of molecular similarity scores

Comparative Molecular Similarity Indices Analysis of 1-(Naphthylalky1)-1H-imidazole Analogs with Antiepileptic Activity

A three-dimensional quantitative structure-activity relationship (3D QSAR) of 44 structurally and functionally diverse series of 1- (Naphthylalkylimidazoles) as antiepileptic agents was studied using the Comparative molecular similarity indices analysis (CoMSIA) method. A training set containing 34 molecules served to establish the models. The optimum CoMSIA model obtained for the training set were all statistically significant, with cross-validated coefficients (q2) of 0.725 and conventional coefficients (r2ncv) of 0.998. The predictive capacities of the model were successfully validated by using a test set of 10 molecules that were not included in the training set. CoMSIA model (Model 1) obtained from the hydrophobic and Hbond acceptor field was found to have the best predictivity, with a predictive correlation coefficient (r2pred) of 0.67. The information obtained from this 3D-QSAR model can be used to guide the development of imidazoles as novel antiepileptic agents

End-to-End Joint Antenna Selection Strategy and Distributed Compress and Forward Strategy for Relay Channels

Multi-hop relay channels use multiple relay stages, each with multiple relay nodes, to facilitate communication between a source and destination. Previously, distributed space-time codes were proposed to maximize the achievable diversity-multiplexing tradeoff, however, they fail to achieve all the points of the optimal diversity-multiplexing tradeoff. In the presence of a low-rate feedback link from the destination to each relay stage and the source, this paper proposes an end-to-end antenna selection (EEAS) strategy as an alternative to distributed space-time codes. The EEAS strategy uses a subset of antennas of each relay stage for transmission of the source signal to the destination with amplify and forwarding at each relay stage. The subsets are chosen such that they maximize the end-to-end mutual information at the destination. The EEAS strategy achieves the corner points of the optimal diversity-multiplexing tradeoff (corresponding to maximum diversity gain and maximum multiplexing gain) and achieves better diversity gain at intermediate values of multiplexing gain, versus the best known distributed space-time coding strategies. A distributed compress and forward (CF) strategy is also proposed to achieve all points of the optimal diversity-multiplexing tradeoff for a two-hop relay channel with multiple relay nodes.Comment: Accepted for publication in the special issue on cooperative communication in the Eurasip Journal on Wireless Communication and Networkin

Radiation hardness qualification of PbWO4 scintillation crystals for the CMS Electromagnetic Calorimeter

This is the Pre-print version of the Article. The official published version can be accessed from the link below - Copyright @ 2010 IOPEnsuring the radiation hardness of PbWO4 crystals was one of the main priorities during the construction of the electromagnetic calorimeter of the CMS experiment at CERN. The production on an industrial scale of radiation hard crystals and their certification over a period of several years represented a difficult challenge both for CMS and for the crystal suppliers. The present article reviews the related scientific and technological problems encountered

Assessment of the quality and variability of health information on chronic pain websites using the DISCERN instrument

<p>Abstract</p> <p>Background</p> <p>The Internet is used increasingly by providers as a tool for disseminating pain-related health information and by patients as a resource about health conditions and treatment options. However, health information on the Internet remains unregulated and varies in quality, accuracy and readability. The objective of this study was to determine the quality of pain websites, and explain variability in quality and readability between pain websites.</p> <p>Methods</p> <p>Five key terms (pain, chronic pain, back pain, arthritis, and fibromyalgia) were entered into the Google, Yahoo and MSN search engines. Websites were assessed using the DISCERN instrument as a quality index. Grade level readability ratings were assessed using the Flesch-Kincaid Readability Algorithm. Univariate (using alpha = 0.20) and multivariable regression (using alpha = 0.05) analyses were used to explain the variability in DISCERN scores and grade level readability using potential for commercial gain, health related seals of approval, language(s) and multimedia features as independent variables.</p> <p>Results</p> <p>A total of 300 websites were assessed, 21 excluded in accordance with the exclusion criteria and 110 duplicate websites, leaving 161 unique sites. About 6.8% (11/161 websites) of the websites offered patients' commercial products for their pain condition, 36.0% (58/161 websites) had a health related seal of approval, 75.8% (122/161 websites) presented information in English only and 40.4% (65/161 websites) offered an interactive multimedia experience. In assessing the quality of the unique websites, of a maximum score of 80, the overall average DISCERN Score was 55.9 (13.6) and readability (grade level) of 10.9 (3.9). The multivariable regressions demonstrated that website seals of approval (<it>P </it>= 0.015) and potential for commercial gain (<it>P </it>= 0.189) were contributing factors to higher DISCERN scores, while seals of approval (<it>P </it>= 0.168) and interactive multimedia (<it>P </it>= 0.244) contributed to lower grade level readability, as indicated by estimates of the beta coefficients.</p> <p>Conclusion</p> <p>The overall quality of pain websites is moderate, with some shortcomings. Websites that scored high using the DISCERN questionnaire contained health related seals of approval and provided commercial solutions for pain related conditions while those with low readability levels offered interactive multimedia options and have been endorsed by health seals.</p

The importance of understanding individual differences in Down syndrome

In this article, we first present a summary of the general assumptions about Down syndrome (DS) still to be found in the literature. We go on to show how new research has modified these assumptions, pointing to a wide range of individual differences at every level of description. We argue that, in the context of significant increases in DS life expectancy, a focus on individual differences in trisomy 21 at all levels—genetic, cellular, neural, cognitive, behavioral, and environmental—constitutes one of the best approaches for understanding genotype/phenotype relations in DS and for exploring risk and protective factors for Alzheimer’s disease in this high-risk population

VASP: A Volumetric Analysis of Surface Properties Yields Insights into Protein-Ligand Binding Specificity

Many algorithms that compare protein structures can reveal similarities that suggest related biological functions, even at great evolutionary distances. Proteins with related function often exhibit differences in binding specificity, but few algorithms identify structural variations that effect specificity. To address this problem, we describe the Volumetric Analysis of Surface Properties (VASP), a novel volumetric analysis tool for the comparison of binding sites in aligned protein structures. VASP uses solid volumes to represent protein shape and the shape of surface cavities, clefts and tunnels that are defined with other methods. Our approach, inspired by techniques from constructive solid geometry, enables the isolation of volumetrically conserved and variable regions within three dimensionally superposed volumes. We applied VASP to compute a comparative volumetric analysis of the ligand binding sites formed by members of the steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domains and the serine proteases. Within both families, VASP isolated individual amino acids that create structural differences between ligand binding cavities that are known to influence differences in binding specificity. Also, VASP isolated cavity subregions that differ between ligand binding cavities which are essential for differences in binding specificity. As such, VASP should prove a valuable tool in the study of protein-ligand binding specificity