Frog: a FRee Online druG 3D conformation generator

In silico screening methods based on the 3D structures of the ligands or of the proteins have become an essential tool to facilitate the drug discovery process. To achieve such process, the 3D structures of the small chemical compounds have to be generated. In addition, for ligand-based screening computations or hierarchical structure-based screening projects involving a rigid-body docking step, it is necessary to generate multi-conformer 3D models for each input ligand to increase the efficiency of the search. However, most academic or commercial compound collections are delivered in 1D SMILES (simplified molecular input line entry system) format or in 2D SDF (structure data file), highlighting the need for free 1D/2D to 3D structure generators. Frog is an on-line service aimed at generating 3D conformations for drug-like compounds starting from their 1D or 2D descriptions. Given the atomic constitution of the molecules and connectivity information, Frog can identify the different unambiguous isomers corresponding to each compound, and generate single or multiple low-to-medium energy 3D conformations, using an assembly process that does not presently consider ring flexibility. Tests show that Frog is able to generate bioactive conformations close to those observed in crystallographic complexes. Frog can be accessed at http://bioserv.rpbs.jussieu.fr/Frog.html

BamView: viewing mapped read alignment data in the context of the reference sequence

Summary: BamView is an interactive Java application for visualizing the large amounts of data stored for sequence reads which are aligned against a reference genome sequence. It supports the BAM (Binary Alignment/Map) format. It can be used in a number of contexts including SNP calling and structural annotation. BamView has also been integrated into Artemis so that the reads can be viewed in the context of the nucleotide sequence and genomic features

Integrated stratigraphy and 40Ar/39Ar chronology of the Early to Middle Miocene Upper Freshwater Molasse in eastern Bavaria (Germany)

A detailed integrated stratigraphic study was carried out on middle Miocene fluvial successions of the Upper Freshwater Molasse (OSM) from the North Alpine Foreland Basin, in eastern Bavaria, Germany. The biostratigraphic investigations yielded six new localities thereby refining the OSM biostratigraphy for units C to E (sensu; Heissig, Actes du Congres BiochroM'1997) and further improving biostratigraphic correlations between the different sections throughout eastern Bavaria. Radioisotopic ages of 14.55 ± 0.19 and 14.88 ± 0.11 Ma have been obtained for glass shards from the main bentonite horizon and the Ries impactite: two important stratigraphic marker beds used for confirming our magnetostratigraphic calibration to the Astronomical Tuned Neogene Time Scale (ATNTS04; Lourens et al. in Geologic Time Scale 2004, Cambridge University Press, 2004). Paleomagnetic analysis was performed using alternating field (AF) and thermal (TH) demagnetization methods. The AF method revealed both normal and reverse polarities but proofs to yield unreliable ChRM directions for the Puttenhausen section. Using the biostratigraphic information and radioisotopic ages, the magnetostratigraphic records of the different sections are tentatively correlated to the Astronomical Tuned Neogene Time Scale (ATNTS04; Lourens et al. in Geologic Time Scale 2004, Cambridge University Press, 2004). This correlation implies that the main bentonite horizon coincides to chron C5ADn, which is corroborated by its radioisotopic age of 14.55 Ma, whereas the new fossil locality Furth 460, belonging to OSM unit E, probably correlates to chron C5Bn.1r. The latter correlation agrees well with the Swiss Molasse locality Frohberg. Correlations of the older sections are not straightforward. The Brock horizon, which comprises limestone ejecta from the Ries impact, possibly correlates to C5ADr (14.581 ± 14.784 Ma), implying that, although within error, the radioisotopic age of 14.88 ± 0.11 Ma is somewhat too old. The fossil localities in Puttenhausen, belonging to the older part of OSM unit C, probably coincide with chron C5Cn.2n or older, which is older than the correlations established for the Swiss Molasse. © Springer-Verlag 2007

[SiPAH]+ pi-Complexes in the Interstellar Medium

We investigate the presence of silicon atoms adsorbed on the surface of interstellar polycyclic aromatic hydrocarbons (PAHs) to form SiPAH pi-complexes. We use quantum chemistry calculations to obtain structural, thermodynamic and mid-IR properties of neutral and cationic SiPAH complexes. The binding energy was found to be at least 1.5 eV for [SiPAH]+ complexes whereas it is roughly 0.5 eV for their neutral counterparts. From the spectral analysis of the calculated IR spectra, we found that the coordination of silicon to PAH+ does not strongly affect the intensities of the PAH+ spectra, but systematically introduces blueshifts of the C-C in-plane and the C-H out-of-plane bands. The thermodynamic data calculated for [SiPAH]+ complexes show that these species are stable and can be easily formed by radiative association of Si+ and PAH species that are known to be abundant in photodissociation regions. Their mid-IR fingerprints show features induced by the coordination of silicon that could account for (i) the blueshifted position of the 6.2 micron AIB and (ii) the presence of satellite bands observed on the blue side of the 6.2 and 11.2 micron AIBs. From such an assignment, we can deduce that typically 1% of the cosmic silicon appears to be attached to PAHs.Comment: Accepted for publication in Astronomy and Astrophysic

Peristaltic Pumping of Blood Through Small Vessels of Varying Cross-section

The paper is devoted to a study of the peristaltic motion of blood in the micro-circulatory system. The vessel is considered to be of varying cross-section. The progressive peristaltic waves are taken to be of sinusoidal nature. Blood is considered to be a Herschel-Bulkley fluid. Of particular concern here is to investigate the effects of amplitude ratio, mean pressure gradient, yield stress and the power law index on the velocity distribution, streamline pattern and wall shear stress. On the basis of the derived analytical expression, extensive numerical calculations have been made. The study reveals that velocity of blood and wall shear stress are appreciably affected due to the non-uniform geometry of blood vessels. They are also highly sensitive to the magnitude of the amplitude ratio and the value of the fluid index.Comment: Accepted for publication in ASME journal of Applied Mechanics. arXiv admin note: text overlap with arXiv:1108.1285v

A selected ion flow tube study of the ion-molecule reactions of monochloroethene, trichloroethene and tetrachloroethene

Data for the rate coefficients and product cations of the reactions of a large number of atomic and small molecular cations with monochloroethene, trichloroethene and tetrachloroethene in a selected ion flow tube at 298 K are reported. The recombination energy of the ions range from 6.27 eV (H$_3$O$^+$) through to 21.56 eV (Ne$^+$). Collisional rate coefficients are calculated by modified average dipole orientation theory and compared with experimental values. Thermochemistry and mass balance predict the most feasible neutral products. Together with previously reported results for the three isomers of dichloroethene (J. Phys. Chem. A., 2006, 110, 5760), the fragment ion branching ratios have been compared with those from threshold photoelectron photoion coincidence spectroscopy over the photon energy range 9-22 eV to determine the importance or otherwise of long-range charge transfer. For ions with recombination energy in excess of the ionisation energy of the chloroethene, charge transfer is energetically allowed. The similarity of the branching ratios from the two experiments suggest that long-range charge transfer is dominant. For ions with recombination energy less than the ionisation energy, charge transfer is not allowed; chemical reaction can only occur following formation of an ion-molecule complex, where steric effects are more significant. The products that are now formed and their percentage yield is a complex interplay between the number and position of the chlorine atoms with respect to the C=C bond, where inductive and conjugation effects can be important

A Survey of HC3N in Extragalactic Sources - Is HC3N a Tracer of Activity in ULIRGs?

Context. HC3N is a molecule that is mainly associated with Galactic star-forming regions, but it has also been detected in extragalactic environments. Aims. To present the first extragalactic survey of HC3N, when combining earlier data from the literature with six new single-dish detections, and to compare HC3N with other molecular tracers (HCN, HNC), as well as other properties (silicate absorption strength, IR flux density ratios, C II flux, and megamaser activity). Methods. We present mm IRAM 30 m, OSO 20 m, and SEST observations of HC3N rotational lines (mainly the J = 10-9 transition) and of the J = 1-0 transitions of HCN and HNC. Our combined HC3N data account for 13 galaxies (excluding the upper limits reported for the non-detections), while we have HCN and HNC data for more than 20 galaxies. Results. A preliminary definition "HC3N-luminous galaxy" is made based upon the HC3N/HCN ratio. Most (~80 %) HC3N-luminous galaxies seem to be deeply obscured galaxies and (U)LIRGs. A majority (~60 % or more) of the HC3N-luminous galaxies in the sample present OH mega- or strong kilomaser activity. A possible explanation is that both HC3N and OH megamasers need warm dust for their excitation. Alternatively, the dust that excites the OH megamaser offers protection against UV destruction of HC3N. A high silicate absorption strength is also found in several of the HC3N-luminous objects, which may help the HC3N to survive. Finally, we find that a high HC3N/HCN ratio is related to a high dust temperature and a low C II flux.Comment: 17 pages, 12 figures, to be published in Astronomy & Astrophysic

Drinking in the dark: shedding light on young people’s alcohol consumption experiences

This paper draws on 12 months of ethnographic research to explore the drinking experiences of young people, aged 15-24, living in the suburban case study locations of Chorlton and Wythenshawe, Manchester, UK. This paper moves beyond the contemporary geographical imaginary of alcohol consumption as a city-centre issue, to explore suburban indoor and outdoor drinking cultures. Through paying attention to atmospheres of darkness and lightness, I show how drinkscapes are active constituents of young people’s drinking occasions, rather than passive backdrops. More than this, I illustrate how young people transform dark and light drinkscapes, thereby shaping the drinking practices of themselves and others. Through looking at the interplay between the curating of an atmosphere, and the experience of that atmosphere when bodies, and practices are inserted into it, this paper offers a different take on the ‘drinking at home is bad, drinking in public spaces is good’ argument, with original policy suggestions

Psychometric evaluation of the Mental Health Quality of Life (MHQoL) instrument in seven European countries

Introduction: To make efficient use of available resources, decision-makers in healthcare may assess the costs and (health) benefits of health interventions. For interventions aimed at improving mental health capturing the full health benefits is an important challenge. The Mental Health Quality of Life (MHQoL) instrument was recently developed to meet this challenge. Evaluating the pyschometric properties of this instrument in different contexts remains important. Methods: A psychometric evaluation of the MHQoL was performed using existing international, cross-sectional data with 7155 respondents from seven European countries (Denmark, France, Germany, Italy, Portugal, The Netherlands, Portugal and the United Kingdom). Reliability was examined by calculating Cronbach’s alpha, a measure of internal consistency of the seven MHQoL dimensions, and by examining the association of the MHQoL sum scores with the MHQoL-VAS scores. Construct validity was examined by calculating Spearman’s rank correlation coefficients between the MHQoL sum scores and EQ-5D index scores, EQ-VAS scores, EQ-5D anxiety/depression dimension scores, ICECAP-A index scores and PHQ-4 sum scores. Results: The MHQoL was found to have good internal consistency for all seven countries. The MHQoL sum score and the MHQoL-VAS had a high correlation. Spearman’s rank correlation coefficients were moderate to very high for all outcomes. Conclusion: Our results, based on data gathered in seven European countries, suggest that the MHQoL shows favourable psychometrical characteristics. While further validation remains important, the MHQoL may be a useful instrument in measuring mental health-related quality of life in the Western European context