64 research outputs found
Evaluation of a Bayesian inference network for ligand-based virtual screening
Background
Bayesian inference networks enable the computation of the probability that an event will occur. They have been used previously to rank textual documents in order of decreasing relevance to a user-defined query. Here, we modify the approach to enable a Bayesian inference network to be used for chemical similarity searching, where a database is ranked in order of decreasing probability of bioactivity.
Results
Bayesian inference networks were implemented using two different types of network and four different types of belief function. Experiments with the MDDR and WOMBAT databases show that a Bayesian inference network can be used to provide effective ligand-based screening, especially when the active molecules being sought have a high degree of structural homogeneity; in such cases, the network substantially out-performs a conventional, Tanimoto-based similarity searching system. However, the effectiveness of the network is much less when structurally heterogeneous sets of actives are being sought.
Conclusion
A Bayesian inference network provides an interesting alternative to existing tools for ligand-based virtual screening
Domain analysis of lipoprotein LppQ in Mycoplasma mycoides subsp. mycoides SC
The lipoprotein LppQ is the most prominent antigen of Mycoplasma mycoides subsp. mycoides small colony type (SC) during infection of cattle. This pathogen causes contagious bovine pleuropneumonia (CBPP), a devastating disease of considerable socio-economic importance in many countries worldwide. The dominant antigenicity and high specificity for M. mycoides subsp. mycoides SC of lipoprotein LppQ have been exploited for serological diagnosis and for epidemiological investigations of CBPP. Scanning electron microscopy and immunogold labelling were used to provide ultrastructural evidence that LppQ is located to the cell membrane at the outer surface of M. mycoides subsp. mycoides SC. The selectivity and specificity of this method were demonstrated through discriminating localization of extracellular (i.e., in the zone of contact with host cells) vs. integral membrane domains of LppQ. Thus, our findings support the suggestion that the accessible N-terminal domain of LppQ is surface exposed and such surface localization may be implicated in the pathogenesis of CBPP
Dark Force Detection in Low Energy e-p Collisions
We study the prospects for detecting a light boson X with mass m_X < 100 MeV
at a low energy electron-proton collider. We focus on the case where X
dominantly decays to e+ e- as motivated by recent "dark force" models. In order
to evade direct and indirect constraints, X must have small couplings to the
standard model (alpha_X 10 MeV).
By comparing the signal and background cross sections for the e- p e+ e- final
state, we conclude that dark force detection requires an integrated luminosity
of around 1 inverse attobarn, achievable with a forthcoming JLab proposal.Comment: 38 pages, 19 figures; v2, references adde
A Spatial Analysis of Rift Valley Fever Virus Seropositivity in Domestic Ruminants in Tanzania
Rift Valley fever (RVF) is an acute arthropod-borne viral zoonotic disease primarily occurring in Africa. Since RVF-like disease was reported in Tanzania in 1930, outbreaks of the disease have been reported mainly from the eastern ecosystem of the Great Rift Valley. This cross-sectional study was carried out to describe the variation in RVF virus (RVFV) seropositivity in domestic ruminants between selected villages in the eastern and western Rift Valley ecosystems in Tanzania, and identify potential risk factors. Three study villages were purposively selected from each of the two Rift Valley ecosystems. Serum samples from randomly selected domestic ruminants (n = 1,435) were tested for the presence of specific immunoglobulin G (IgG) and M (IgM), using RVF enzyme-linked immunosorbent assay methods. Mixed effects logistic regression modelling was used to investigate the association between potential risk factors and RVFV seropositivity. The overall RVFV seroprevalence (n = 1,435) in domestic ruminants was 25.8% and species specific seroprevalence was 29.7%, 27.7% and 22.0% in sheep (n = 148), cattle (n = 756) and goats (n = 531), respectively. The odds of seropositivity were significantly higher in animals sampled from the villages in the eastern than those in the western Rift Valley ecosystem (OR = 1.88, CI: 1.41, 2.51; p<0.001), in animals sampled from villages with soils of good than those with soils of poor water holding capacity (OR = 1.97; 95% CI: 1.58, 3.02; p< 0.001), and in animals which had been introduced than in animals born within the herd (OR = 5.08, CI: 2.74, 9.44; p< 0.001). Compared with animals aged 1-2 years, those aged 3 and 4-5 years had 3.40 (CI: 2.49, 4.64; p< 0.001) and 3.31 (CI: 2.27, 4.82, p< 0.001) times the odds of seropositivity. The findings confirm exposure to RVFV in all the study villages, but with a higher prevalence in the study villages from the eastern Rift Valley ecosystem
An Electron Fixed Target Experiment to Search for a New Vector Boson A' Decaying to e+e-
We describe an experiment to search for a new vector boson A' with weak
coupling alpha' > 6 x 10^{-8} alpha to electrons (alpha=e^2/4pi) in the mass
range 65 MeV < m_A' < 550 MeV. New vector bosons with such small couplings
arise naturally from a small kinetic mixing of the "dark photon" A' with the
photon -- one of the very few ways in which new forces can couple to the
Standard Model -- and have received considerable attention as an explanation of
various dark matter related anomalies. A' bosons are produced by radiation off
an electron beam, and could appear as narrow resonances with small production
cross-section in the trident e+e- spectrum. We summarize the experimental
approach described in a proposal submitted to Jefferson Laboratory's PAC35,
PR-10-009. This experiment, the A' Experiment (APEX), uses the electron beam of
the Continuous Electron Beam Accelerator Facility at Jefferson Laboratory
(CEBAF) at energies of ~1-4 GeV incident on 0.5-10% radiation length Tungsten
wire mesh targets, and measures the resulting e+e- pairs to search for the A'
using the High Resolution Spectrometer and the septum magnet in Hall A. With a
~1 month run, APEX will achieve very good sensitivity because the statistics of
e+e- pairs will be ~10,000 times larger in the explored mass range than any
previous search for the A' boson. These statistics and the excellent mass
resolution of the spectrometers allow sensitivity to alpha'/alpha one to three
orders of magnitude below current limits, in a region of parameter space of
great theoretical and phenomenological interest. Similar experiments could also
be performed at other facilities, such as the Mainz Microtron.Comment: 19 pages, 12 figures, 2 table
Specific Evolution of F1-Like ATPases in Mycoplasmas
F1F0 ATPases have been identified in most bacteria, including mycoplasmas which have very small genomes associated with a host-dependent lifestyle. In addition to the typical operon of eight genes encoding genuine F1F0 ATPase (Type 1), we identified related clusters of seven genes in many mycoplasma species. Four of the encoded proteins have predicted structures similar to the α, ÎČ, Îł and Δ subunits of F1 ATPases and could form an F1-like ATPase. The other three proteins display no similarity to any other known proteins. Two of these proteins are probably located in the membrane, as they have three and twelve predicted transmembrane helices. Phylogenomic studies identified two types of F1-like ATPase clusters, Type 2 and Type 3, characterized by a rapid evolution of sequences with the conservation of structural features. Clusters encoding Type 2 and Type 3 ATPases were assumed to originate from the Hominis group of mycoplasmas. We suggest that Type 3 ATPase clusters may spread to other phylogenetic groups by horizontal gene transfer between mycoplasmas in the same host, based on phylogeny and genomic context. Functional analyses in the ruminant pathogen Mycoplasma mycoides subsp. mycoides showed that the Type 3 cluster genes were organized into an operon. Proteomic analyses demonstrated that the seven encoded proteins were produced during growth in axenic media. Mutagenesis and complementation studies demonstrated an association of the Type 3 cluster with a major ATPase activity of membrane fractions. Thus, despite their tendency toward genome reduction, mycoplasmas have evolved and exchanged specific F1-like ATPases with no known equivalent in other bacteria. We propose a model, in which the F1-like structure is associated with a hypothetical X0 sector located in the membrane of mycoplasma cells
Genetic Networking of the Bemisia tabaci Cryptic Species Complex Reveals Pattern of Biological Invasions
BACKGROUND: A challenge within the context of cryptic species is the delimitation of individual species within the complex. Statistical parsimony network analytics offers the opportunity to explore limits in situations where there are insufficient species-specific morphological characters to separate taxa. The results also enable us to explore the spread in taxa that have invaded globally. METHODOLOGY/PRINCIPAL FINDINGS: Using a 657 bp portion of mitochondrial cytochrome oxidase 1 from 352 unique haplotypes belonging to the Bemisia tabaci cryptic species complex, the analysis revealed 28 networks plus 7 unconnected individual haplotypes. Of the networks, 24 corresponded to the putative species identified using the rule set devised by Dinsdale et al. (2010). Only two species proposed in Dinsdale et al. (2010) departed substantially from the structure suggested by the analysis. The analysis of the two invasive members of the complex, Mediterranean (MED) and Middle East - Asia Minor 1 (MEAM1), showed that in both cases only a small number of haplotypes represent the majority that have spread beyond the home range; one MEAM1 and three MED haplotypes account for >80% of the GenBank records. Israel is a possible source of the globally invasive MEAM1 whereas MED has two possible sources. The first is the eastern Mediterranean which has invaded only the USA, primarily Florida and to a lesser extent California. The second are western Mediterranean haplotypes that have spread to the USA, Asia and South America. The structure for MED supports two home range distributions, a Sub-Saharan range and a Mediterranean range. The MEAM1 network supports the Middle East - Asia Minor region. CONCLUSION/SIGNIFICANCE: The network analyses show a high level of congruence with the species identified in a previous phylogenetic analysis. The analysis of the two globally invasive members of the complex support the view that global invasion often involve very small portions of the available genetic diversity
Supernova remnants: the X-ray perspective
Supernova remnants are beautiful astronomical objects that are also of high
scientific interest, because they provide insights into supernova explosion
mechanisms, and because they are the likely sources of Galactic cosmic rays.
X-ray observations are an important means to study these objects.And in
particular the advances made in X-ray imaging spectroscopy over the last two
decades has greatly increased our knowledge about supernova remnants. It has
made it possible to map the products of fresh nucleosynthesis, and resulted in
the identification of regions near shock fronts that emit X-ray synchrotron
radiation.
In this text all the relevant aspects of X-ray emission from supernova
remnants are reviewed and put into the context of supernova explosion
properties and the physics and evolution of supernova remnants. The first half
of this review has a more tutorial style and discusses the basics of supernova
remnant physics and thermal and non-thermal X-ray emission. The second half
offers a review of the recent advances.The topics addressed there are core
collapse and thermonuclear supernova remnants, SN 1987A, mature supernova
remnants, mixed-morphology remnants, including a discussion of the recent
finding of overionization in some of them, and finally X-ray synchrotron
radiation and its consequences for particle acceleration and magnetic fields.Comment: Published in Astronomy and Astrophysics Reviews. This version has 2
column-layout. 78 pages, 42 figures. This replaced version has some minor
language edits and several references have been correcte
A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)
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