94 research outputs found
On evaluating moleculardocking methods for pose prediction and enrichment factors.
Four of the most well-known, commercially available docking programs, FlexX, GOLD, GLIDE, and ICM, have been examined for their ligand-docking and virtual-screening capabilities. The relative performance of the programs in reproducing the native ligand conformation from starting SMILES strings for 164 highresolution protein-ligand complexes is presented and compared. Applying only the native scoring functions, the latest versions of these four docking programs were also used to conduct virtual screening for 12 protein targets of therapeutic interest, involving both publicly available structures and AstraZeneca in-house structures. The capability of the four programs to correctly rank-order target-specific active compounds over alternative binders and nonbinders (decoys plus randomly selected compounds) and thereby enrich a small subset of a screening library is compared. Enrichments from the virtual-screening experiments are contrasted with those obtained with alternative 3D shape-matching and 2D similarity database-search methods
The modENCODE Data Coordination Center: lessons in harvesting comprehensive experimental details.
The model organism Encyclopedia of DNA Elements (modENCODE) project is a National Human Genome Research Institute (NHGRI) initiative designed to characterize the genomes of Drosophila melanogaster and Caenorhabditis elegans. A Data Coordination Center (DCC) was created to collect, store and catalog modENCODE data. An effective DCC must gather, organize and provide all primary, interpreted and analyzed data, and ensure the community is supplied with the knowledge of the experimental conditions, protocols and verification checks used to generate each primary data set. We present here the design principles of the modENCODE DCC, and describe the ramifications of collecting thorough and deep metadata for describing experiments, including the use of a wiki for capturing protocol and reagent information, and the BIR-TAB specification for linking biological samples to experimental results. modENCODE data can be found at http://www.modencode.org
A powerful bursting radio source towards the Galactic Centre
Transient astronomical sources are typically powered by compact objects and
usually signify highly explosive or dynamic events. While radio astronomy has
an impressive record of obtaining high time resolution observations, usually it
is achieved in quite narrow fields-of-view. Consequently, the dynamic radio sky
is poorly sampled, in contrast to the situation in the X- and gamma-ray bands
in which wide-field instruments routinely detect transient sources. Here we
report a new transient source, GCRT J1745-3009, detected in 2002 during a
moderately wide-field radio transient monitoring program of the Galactic center
(GC) region at 0.33 GHz. The characteristics of its bursts are unlike those
known for any other class of radio transient. If located in or near the GC, its
brightness temperature (~10^16 K) and the implied energy density within GCRT
J1745-3009 vastly exceeds that observed in most other classes of radio
astronomical sources, and is consistent with coherent emission processes rarely
observed. We conclude that GCRT J1745-3009 is the first member of a new class
of radio transient sources, the first of possibly many new classes to be
identified through current and upcoming radio surveys.Comment: 16 pages including 3 figures. Appears in Nature, 3 March 200
Populating the Galaxy with pulsars I: stellar & binary evolution
The computation of theoretical pulsar populations has been a major component
of pulsar studies since the 1970s. However, the majority of pulsar population
synthesis has only regarded isolated pulsar evolution. Those that have examined
pulsar evolution within binary systems tend to either treat binary evolution
poorly or evolve the pulsar population in an ad-hoc manner. Thus no complete
and direct comparison with observations of the pulsar population within the
Galactic disk has been possible to date. Described here is the first component
of what will be a complete synthetic pulsar population survey code. This
component is used to evolve both isolated and binary pulsars. Synthetic
observational surveys can then be performed on this population for a variety of
radio telescopes. The final tool used for completing this work will be a code
comprised of three components: stellar/binary evolution, Galactic kinematics
and survey selection effects. Results provided here support the need for
further (apparent) pulsar magnetic field decay during accretion, while they
conversely suggest the need for a re-evaluation of the assumed \textit{typical}
MSP formation process. Results also focus on reproducing the observed
diagram for Galactic pulsars and how this precludes short timescales
for standard pulsar exponential magnetic field decay. Finally, comparisons of
bulk pulsar population characteristics are made to observations displaying the
predictive power of this code, while we also show that under standard binary
evolutionary assumption binary pulsars may accrete much mass.Comment: 26 pages, 16 figures, 1 table, accepted for publication in MNRA
modMine: flexible access to modENCODE data.
In an effort to comprehensively characterize the functional elements within the genomes of the important model organisms Drosophila melanogaster and Caenorhabditis elegans, the NHGRI model organism Encyclopaedia of DNA Elements (modENCODE) consortium has generated an enormous library of genomic data along with detailed, structured information on all aspects of the experiments. The modMine database (http://intermine.modencode.org) described here has been built by the modENCODE Data Coordination Center to allow the broader research community to (i) search for and download data sets of interest among the thousands generated by modENCODE; (ii) access the data in an integrated form together with non-modENCODE data sets; and (iii) facilitate fine-grained analysis of the above data. The sophisticated search features are possible because of the collection of extensive experimental metadata by the consortium. Interfaces are provided to allow both biologists and bioinformaticians to exploit these rich modENCODE data sets now available via modMine
EDULISS: a small-molecule database with data-mining and pharmacophore searching capabilities
We present the relational database EDULISS (EDinburgh University Ligand Selection System), which stores structural, physicochemical and pharmacophoric properties of small molecules. The database comprises a collection of over 4 million commercially available compounds from 28 different suppliers. A user-friendly web-based interface for EDULISS (available at http://eduliss.bch.ed.ac.uk/) has been established providing a number of data-mining possibilities. For each compound a single 3D conformer is stored along with over 1600 calculated descriptor values (molecular properties). A very efficient method for unique compound recognition, especially for a large scale database, is demonstrated by making use of small subgroups of the descriptors. Many of the shape and distance descriptors are held as pre-calculated bit strings permitting fast and efficient similarity and pharmacophore searches which can be used to identify families of related compounds for biological testing. Two ligand searching applications are given to demonstrate how EDULISS can be used to extract families of molecules with selected structural and biophysical features
Erratum: 'A precise mass measurement of the intermediate-mass binary pulsar PSR J1802-2124' (2010, ApJ, 711, 764)
Figure 1 as originally published did not match its corresponding caption; although the image was meant to be updated, it was unintentionally left unchanged. The correct Figure 1 with its corresponding caption is shown below
The CCR4-NOT Complex Is Implicated in the Viability of Aneuploid Yeasts
To identify the genes required to sustain aneuploid viability, we screened a deletion library of non-essential genes in the fission yeast Schizosaccharomyces pombe, in which most types of aneuploidy are eventually lethal to the cell. Aneuploids remain viable for a period of time and can form colonies by reducing the extent of the aneuploidy. We hypothesized that a reduction in colony formation efficiency could be used to screen for gene deletions that compromise aneuploid viability. Deletion mutants were used to measure the effects on the viability of spores derived from triploid meiosis and from a chromosome instability mutant. We found that the CCR4-NOT complex, an evolutionarily conserved general regulator of mRNA turnover, and other related factors, including poly(A)-specific nuclease for mRNA decay, are involved in aneuploid viability. Defective mutations in CCR4-NOT complex components in the distantly related yeast Saccharomyces cerevisiae also affected the viability of spores produced from triploid cells, suggesting that this complex has a conserved role in aneuploids. In addition, our findings suggest that the genes required for homologous recombination repair are important for aneuploid viability
Tracking Under-Reported Financial Flows: China's Development Finance and the Aid-Conflict Nexus Revisited
Validation of the Body Concealment Scale for Scleroderma (BCSS): Replication in the Scleroderma Patient-centered Intervention Network (SPIN) Cohort
© 2016 Elsevier Ltd Body concealment is an important component of appearance distress for individuals with disfiguring conditions, including scleroderma. The objective was to replicate the validation study of the Body Concealment Scale for Scleroderma (BCSS) among 897 scleroderma patients. The factor structure of the BCSS was evaluated using confirmatory factor analysis and the Multiple-Indicator Multiple-Cause model examined differential item functioning of SWAP items for sex and age. Internal consistency reliability was assessed via Cronbach's alpha. Construct validity was assessed by comparing the BCSS with a measure of body image distress and measures of mental health and pain intensity. Results replicated the original validation study, where a bifactor model provided the best fit. The BCSS demonstrated strong internal consistency reliability and construct validity. Findings further support the BCSS as a valid measure of body concealment in scleroderma and provide new evidence that scores can be compared and combined across sexes and ages
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