A tree-based method for the rapid screening of chemical fingerprints

<p>Abstract</p> <p>Background</p> <p>The fingerprint of a molecule is a bitstring based on its structure, constructed such that structurally similar molecules will have similar fingerprints. Molecular fingerprints can be used in an initial phase of drug development for identifying novel drug candidates by screening large databases for molecules with fingerprints similar to a query fingerprint.</p> <p>Results</p> <p>In this paper, we present a method which efficiently finds all fingerprints in a database with Tanimoto coefficient to the query fingerprint above a user defined threshold. The method is based on two novel data structures for rapid screening of large databases: the <it>k</it>D grid and the Multibit tree. The <it>k</it>D grid is based on splitting the fingerprints into <it>k </it>shorter bitstrings and utilising these to compute bounds on the similarity of the complete bitstrings. The Multibit tree uses hierarchical clustering and similarity within each cluster to compute similar bounds. We have implemented our method and tested it on a large real-world data set. Our experiments show that our method yields approximately a three-fold speed-up over previous methods.</p> <p>Conclusions</p> <p>Using the novel <it>k</it>D grid and Multibit tree significantly reduce the time needed for searching databases of fingerprints. This will allow researchers to (1) perform more searches than previously possible and (2) to easily search large databases.</p

Centimeter-long electron transport in marine sediments via conductive minerals

© 2015 International Society for Microbial Ecology All rights reserved. Centimeter-long electron conduction through marine sediments, in which electrons derived from sulfide in anoxic sediments are transported to oxygen in surficial sediments, may have an important influence on sediment geochemistry. Filamentous bacteria have been proposed to mediate the electron transport, but the filament conductivity could not be verified and other mechanisms are possible. Surprisingly, previous investigations have never actually measured the sediment conductivity or its basic physical properties. Here we report direct measurements that demonstrate centimeter-long electron flow through marine sediments, with conductivities sufficient to account for previously estimated electron fluxes. Conductivity was lost for oxidized sediments, which contrasts with the previously described increase in the conductivity of microbial biofilms upon oxidation. Adding pyrite to the sediments significantly enhanced the conductivity. These results suggest that the role of conductive minerals, which are more commonly found in sediments than centimeter-long microbial filaments, need to be considered when modeling marine sediment biogeochemistry

Changes in the metabolic potential of the sponge microbiome under ocean acidification.

Anthropogenic CO2 emissions are causing ocean acidification, which can affect the physiology of marine organisms. Here we assess the possible effects of ocean acidification on the metabolic potential of sponge symbionts, inferred by metagenomic analyses of the microbiomes of two sponge species sampled at a shallow volcanic CO2 seep and a nearby control reef. When comparing microbial functions between the seep and control sites, the microbiome of the sponge Stylissa flabelliformis (which is more abundant at the control site) exhibits at the seep reduced potential for uptake of exogenous carbohydrates and amino acids, and for degradation of host-derived creatine, creatinine and taurine. The microbiome of Coelocarteria singaporensis (which is more abundant at the seep) exhibits reduced potential for carbohydrate import at the seep, but greater capacity for archaeal carbon fixation via the 3-hydroxypropionate/4-hydroxybutyrate pathway, as well as archaeal and bacterial urea production and ammonia assimilation from arginine and creatine catabolism. Together these metabolic features might contribute to enhanced tolerance of the sponge symbionts, and possibly their host, to ocean acidification

Elemental distributions and mineral parageneses of the Skaergaard PGE-Au mineralisation: consequences of accumulation, redistribution, and equilibration in an upward-migrating mush zone

This is the author accepted manuscript. The final version is available from Oxford University Press via the DOI in this recordThe Skaergaard PGE-Au mineralisation, aka the Platinova Reef, is a syn-magmatic Platinum Group Element (PGE) and gold (Au) mineralisation that formed after crystallisation of ∼74% of the bulk melt of the intrusion. It is hosted in a more than 600 m deep and bowl-shaped succession of gabbroic macro-rhythmic layers in the upper 100 m of the Middle Zone. The precious metal mineralisation comprises a series of concordant, but compositionally zoned, mineralisation levels identified by distinct PGE, Au and Cu peaks. They formed due to local sulphide saturation in stratiform concentrations of interstitial and evolved mush melts in six MLs over > 2000 years. The PGE-Au mineralisation is compared to a stack of gold-rimmed saucers of PGE-rich gabbro of upward decreasing size. Fundamentally different crystallisation and mineralisation scenarios have been proposed for the mineralisation, including offset reef type models based on sulphide saturation in the melt from which the silicate host crystallised, and the here argued model which restricts the same processes to the melt of the inward migrating mush zone of the magma chamber. The latter is supported by: i) a 3D summary of the parageneses of precious metal minerals and phases (> 4000 grains) from 32 samples across the mineralisation; ii) a 3D compilation of all bulk rock assay data; and iii) a principal component analysis (PCA) of PGE, Au, Cu, and selected major and trace elements. In the main PGE-mineralisation level (Pd5 alias Pd-Zone) the precious metal mineral paragenesis varies across the intrusion with precious metal sulphides and Au-alloys at the W-margin to Precambrian basement, precious metal plumbide and Au- and Ag alloys at the E-margin to flood basalts, and skaergaardite (PdCu) and intermetallic compounds and alloys of PGE-Au and Cu in the central parts of the mineralisation. Precious metal parageneses are distinct for a given sector of the intrusion, i.e., drill core (local control), rather than for a given stratigraphic or temporal interval in the accumulated gabbros. The precious metal “grade times width” number (average g/t x metres) for the mineralisation at an upper and a lower cut off of 100 ppb PGE or Au increases from ∼20 to ∼45 g toward the centre of the mineralisation due to ponding of precious metal bearing melt. A strong increase in (Pd+Pt+Au)/Cu and dominance of (PdCu) alloys in the lower and central parts of the mineralisation demonstrate the partial dissolution of droplets of Cu-rich sulphide melt and fractionation of precious metal ratios. The precious metal parageneses, the distribution of precious metals in the mineralisation, and the PCA support initial accumulation of precious metals in the melt of the mush in the floor, followed by equilibration, sulphide saturation, and reactions with residual and immiscible Fe-rich silicate melt in a series of macro-rhythmic layers in the stratified and upward migrating mush zone in the floor of the magma chamber. Syn-magmatic and upward redistribution of precious metals sets the Skaergaard PGE-Au Mineralisation apart from conventional reef type and offset-reef type precious metal mineralisations, and characterize “Skaergaard type” precious metal deposits.Geological Survey of Denmark and Greenlan

Digestibility in selected rainbow trout families and modelling of growth from the specific intake of digestible protein

The experiments aimed to clarify variations in digestibility of dietary nutrients in rainbow trout. Furthermore, the objective was to study how differences in digestibility might be related to growth and feed utilisation at various growth rates. When comparing the results from the experiments it appeared that particularly protein digestibility was closely related to specific growth rate and feed conversion ratio at high growth rates. As a tool to visualise the relationship between protein digestibility and growth of rainbow trout a growth model was developed based on the specific intake of digestible protein, and general assumptions on protein content and protein retention efficiency in rainbow trout. The model indicated that increased protein digestibility only partly explained growth increase and that additional factors were important for growth increment

Vortices on Orbifolds

The Abelian and non-Abelian vortices on orbifolds are investigated based on the moduli matrix approach, which is a powerful method to deal with the BPS equation. The moduli space and the vortex collision are discussed through the moduli matrix as well as the regular space. It is also shown that a quiver structure is found in the Kahler quotient, and a half of ADHM is obtained for the vortex theory on the orbifolds as the case before orbifolding.Comment: 25 pages, 4 figures; references adde

Health literacy, health status, and healthcare utilization of Taiwanese adults: results from a national survey

Abstract Background Low health literacy is considered a worldwide health threat. The purpose of this study is to assess the prevalence and socio-demographic covariates of low health literacy in Taiwanese adults and to investigate the relationships between health literacy and health status and health care utilization. Methods A national survey of 1493 adults was conducted in 2008. Health literacy was measured using the Mandarin Health Literacy Scale. Health status was measured based on self-rated physical and mental health. Health care utilization was measured based on self-reported outpatient clinic visits, emergency room visits, and hospitalizations. Results Approximately thirty percent of adults were found to have low (inadequate or marginal) health literacy. They tended to be older, have fewer years of schooling, lower household income, and reside in less populated areas. Inadequate health literacy was associated with poorer mental health (OR, 0.57; 95% CI, 0.35-0.91). No association was found between health literacy and health care utilization even after adjusting for other covariates. Conclusions Low (inadequate and marginal) health literacy is prevalent in Taiwan. High prevalence of low health literacy is not necessarily indicative of the need for interventions. Systematic efforts to evaluate the impact of low health literacy on health outcomes in other countries would help to illuminate features of health care delivery and financing systems that may mitigate the adverse health effects of low health literacy.http://deepblue.lib.umich.edu/bitstream/2027.42/78252/1/1471-2458-10-614.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78252/2/1471-2458-10-614.pdfPeer Reviewe

Genomic characterization of five deletions in the LDL receptor gene in Danish Familial Hypercholesterolemic subjects

BACKGROUND: Familial Hypercholesterolemia is a common autosomal dominantly inherited disease that is most frequently caused by mutations in the gene encoding the receptor for low density lipoproteins (LDLR). Deletions and other major structural rearrangements of the LDLR gene account for approximately 5% of the mutations in many populations. METHODS: Five genomic deletions in the LDLR gene were characterized by amplification of mutated alleles and sequencing to identify genomic breakpoints. A diagnostic assay based on duplex PCR for the exon 7 – 8 deletion was developed to discriminate between heterozygotes and normals, and bioinformatic analyses were used to identify interspersed repeats flanking the deletions. RESULTS: In one case 15 bp had been inserted at the site of the deleted DNA, and, in all five cases, Alu elements flanked the sites where deletions had occurred. An assay developed to discriminate the wildtype and the deletion allele in a simple duplex PCR detected three FH patients as heterozygotes, and two individuals with normal lipid values were detected as normal homozygotes. CONCLUSION: The identification of the breakpoints should make it possible to develop specific tests for these mutations, and the data provide further evidence for the role of Alu repeats in intragenic deletions

Photometric redshifts for supernovae Ia in the Supernova Legacy Survey

We present a method using the SALT2 light curve fitter to determine the redshift of Type Ia supernovae in the Supernova Legacy Survey (SNLS) based on their photometry in g', r', i' and z'. On 289 supernovae of the first three years of SNLS data, we obtain a precision $\sigma_{\Delta z/(1+z)} = 0.022$ on average up to a redshift of 1.0, with a higher precision of 0.016 for z<0.45 and a lower one of 0.025 for z>0.45. The rate of events with $|\Delta z|/(1+z)>0.15$ (catastrophic errors) is 1.4%. Both the precision and the rate of catastrophic errors are better than what can be currently obtained using host galaxy photometric redshifts. Photometric redshifts of this precision may be useful for future experiments which aim to discover up to millions of supernovae Ia but without spectroscopy for most of them.Comment: 7 pages, 9 figures, published in Astronomy and Astrophysic