3,731 research outputs found

    Fidelity of SNP array genotyping using Epstein Barr virus-transformed B-lymphocyte cell lines: Implications for genome-wide association studies

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    Background: As availability of primary cells can be limited for genetic studies of human disease, lymphoblastoid cell lines (LCL) are common sources of genomic DNA. LCL are created in a transformation process that entails in vitro infection of human B-lymphocytes with the Epstein-Barr Virus (EBV). Methodology/Principal Findings: To test for genotypic errors potentially induced by the Epstein-Barr Virus transformation process, we compared single nucleotide polymorphism (SNP) genotype calls in peripheral blood mononuclear cells (PBMC) and LCL from the same individuals. The average mismatch rate across 19 comparisons was 0.12% for SNPs with a population call rate of at least 95%, and 0.03% at SNPs with a call rate of at least 99%. Mismatch rates were not correlated across genotype subarrays run on all sample pairs. Conclusions/Significance: Genotypic discrepancies found in PBMC and LCL pairs were not significantly different than control pairs, and were not correlated across subarrays. These results suggest that mismatch rates are minimal with stringent quality control, and that most genotypic discrepancies are due to technical artifacts rather than the EBV transformation process. Thus, LCL likely constitute a reliable DNA source for host genotype analysis. © 2009 Herbeck et al

    A dynamic model for nozzle clog monitoring in fused deposition modelling

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    © Emerald Publishing Limited. Purpose - Fused deposition modelling (FDM) is one of the most popular additive manufacturing processes, and is widely used for prototyping and fabricating low-cost customized parts. Current FDM machines have limited techniques to monitor process conditions to minimize process errors, such as nozzle clogging. Nozzle clogging is one of the most significant process errors in current FDM machines, and may cause serious consequences such as print failure. This paper aims to present a physics-based dynamic model suitable for monitoring nozzle clogging in FDM machines. Design/methodology/approach - Liquefier mount of an FDM extruder is analysed as a beam excited by a uniform loading distributed over a partial length. Boundary conditions and applied loads for a direct-type FDM extruder are identified and discussed. Simulation of nozzle clogging was performed by using nozzles of different diameters from 0.5 to 0.2 mm, in step change of 0.1 mm. Sets of experiments were carried out by measuring vibrations of the liquefier block mount during FDM extrusion. Findings - The mount of a liquefier block in an FDM extruder can be used to place a vibration sensor to monitor process errors such as nozzle clogging. Liquefier block mount's transverse vibration amplitudes increase non-linearly when nozzle starts to block. Practical implications - The proposed model can be effectively used for monitoring nozzle clogging in FDM machines, as it is based on the physics relating the FDM process parameters and the nozzle blockage. Originality/value - The novelty of this paper is the unique method of modelling the FDM process dynamics that can be used for monitoring nozzle clogging

    Expression of Ki-67 and Bcl-2 in gastric epithelial cells: role of antralization in gastric carcinogenesis

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    Hazy Blue Worlds:A Holistic Aerosol Model for Uranus and Neptune, Including Dark Spots

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    We present a reanalysis (using the Minnaert limb-darkening approximation) of visible/near-infrared (0.3 - 2.5 micron) observations of Uranus and Neptune made by several instruments. We find a common model of the vertical aerosol distribution that is consistent with the observed reflectivity spectra of both planets, consisting of: 1) a deep aerosol layer with a base pressure > 5-7 bar, assumed to be composed of a mixture of H2S ice and photochemical haze; 2) a layer of photochemical haze/ice, coincident with a layer of high static stability at the methane condensation level at 1-2 bar; and 3) an extended layer of photochemical haze, likely mostly of the same composition as the 1-2-bar layer, extending from this level up through to the stratosphere, where the photochemical haze particles are thought to be produced. For Neptune, we find that we also need to add a thin layer of micron-sized methane ice particles at ~0.2 bar to explain the enhanced reflection at longer methane-absorbing wavelengths. We suggest that methane condensing onto the haze particles at the base of the 1-2-bar aerosol layer forms ice/haze particles that grow very quickly to large size and immediately 'snow out' (as predicted by Carlson et al. 1988), re-evaporating at deeper levels to release their core haze particles to act as condensation nuclei for H2S ice formation. In addition, we find that the spectral characteristics of 'dark spots', such as the Voyager-2/ISS Great Dark Spot and the HST/WFC3 NDS-2018, are well modelled by a darkening or possibly clearing of the deep aerosol layer only.Comment: 58 pages, 23 figures, 4 table

    Hazy Blue Worlds:A Holistic Aerosol Model for Uranus and Neptune, Including Dark Spots

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    We present a reanalysis (using the Minnaert limb-darkening approximation) of visible/near-infrared (0.3 - 2.5 micron) observations of Uranus and Neptune made by several instruments. We find a common model of the vertical aerosol distribution that is consistent with the observed reflectivity spectra of both planets, consisting of: 1) a deep aerosol layer with a base pressure > 5-7 bar, assumed to be composed of a mixture of H2S ice and photochemical haze; 2) a layer of photochemical haze/ice, coincident with a layer of high static stability at the methane condensation level at 1-2 bar; and 3) an extended layer of photochemical haze, likely mostly of the same composition as the 1-2-bar layer, extending from this level up through to the stratosphere, where the photochemical haze particles are thought to be produced. For Neptune, we find that we also need to add a thin layer of micron-sized methane ice particles at ~0.2 bar to explain the enhanced reflection at longer methane-absorbing wavelengths. We suggest that methane condensing onto the haze particles at the base of the 1-2-bar aerosol layer forms ice/haze particles that grow very quickly to large size and immediately 'snow out' (as predicted by Carlson et al. 1988), re-evaporating at deeper levels to release their core haze particles to act as condensation nuclei for H2S ice formation. In addition, we find that the spectral characteristics of 'dark spots', such as the Voyager-2/ISS Great Dark Spot and the HST/WFC3 NDS-2018, are well modelled by a darkening or possibly clearing of the deep aerosol layer only.Comment: 58 pages, 23 figures, 4 table

    Effects of ischaemic conditioning on major clinical outcomes in people undergoing invasive procedures: systematic review and meta-analysis.

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    OBJECTIVE:  To summarise the benefits and harms of ischaemic conditioning on major clinical outcomes in various settings. DESIGN:  Systematic review and meta-analysis. DATA SOURCES:  Medline, Embase, Cochrane databases, and International Clinical Trials Registry platform from inception through October 2015. STUDY SELECTION:  All randomised controlled comparisons of the effect of ischaemic conditioning on clinical outcomes were included. DATA EXTRACTION:  Two authors independently extracted data from individual reports. Reports of multiple intervention arms were treated as separate trials. Random effects models were used to calculate summary estimates for all cause mortality and other pre-specified clinical outcomes. All cause mortality and secondary outcomes with P<0.1 were examined for study quality by using the GRADE assessment tool, the effect of pre-specified characteristics by using meta-regression and Cochran C test, and trial sequential analysis by using the Copenhagen Trial Unit method. RESULTS:  85 reports of 89 randomised comparisons were identified, with a median 80 (interquartile range 60-149) participants and median 1 (range 1 day-72 months) month intended duration. Ischaemic conditioning had no effect on all cause mortality (68 comparisons; 424 events; 11 619 participants; risk ratio 0.96, 95% confidence interval 0.80 to 1.16; P=0.68; moderate quality evidence) regardless of the clinical setting in which it was used or the particular intervention related characteristics. Ischaemic conditioning may reduce the rates of some secondary outcomes including stroke (18 trials; 5995 participants; 149 events; risk ratio 0.72, 0.52 to 1.00; P=0.048; very low quality evidence) and acute kidney injury (36 trials; 8493 participants; 1443 events; risk ratio 0.83, 0.71 to 0.97; P=0.02; low quality evidence), although the benefits seem to be confined to non-surgical settings and to mild episodes of acute kidney injury only. CONCLUSIONS:  Ischaemic conditioning has no overall effect on the risk of death. Possible effects on stroke and acute kidney injury are uncertain given methodological concerns and low event rates. Adoption of ischaemic conditioning cannot be recommended for routine use unless further high quality and well powered evidence shows benefit

    The biofilm matrix scaffold of Pseudomonas aeruginosa contains G-quadruplex extracellular DNA structures.

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    Extracellular DNA, or eDNA, is recognised as a critical biofilm component; however, it is not understood how it forms networked matrix structures. Here, we isolate eDNA from static-culture Pseudomonas aeruginosa biofilms using ionic liquids to preserve its biophysical signatures of fluid viscoelasticity and the temperature dependency of DNA transitions. We describe a loss of eDNA network structure as resulting from a change in nucleic acid conformation, and propose that its ability to form viscoelastic structures is key to its role in building biofilm matrices. Solid-state analysis of isolated eDNA, as a proxy for eDNA structure in biofilms, reveals non-canonical Hoogsteen base pairs, triads or tetrads involving thymine or uracil, and guanine, suggesting that the eDNA forms G-quadruplex structures. These are less abundant in chromosomal DNA and disappear when eDNA undergoes conformation transition. We verify the occurrence of G-quadruplex structures in the extracellular matrix of intact static and flow-cell biofilms of P. aeruginosa, as displayed by the matrix to G-quadruplex-specific antibody binding, and validate the loss of G-quadruplex structures in vivo to occur coincident with the disappearance of eDNA fibres. Given their stability, understanding how extracellular G-quadruplex structures form will elucidate how P. aeruginosa eDNA builds viscoelastic networks, which are a foundational biofilm property

    Swings between rotation and accretion power in a millisecond binary pulsar

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    It is thought that neutron stars in low-mass binary systems can accrete matter and angular momentum from the companion star and be spun-up to millisecond rotational periods. During the accretion stage, the system is called a low-mass X-ray binary, and bright X-ray emission is observed. When the rate of mass transfer decreases in the later evolutionary stages, these binaries host a radio millisecond pulsar whose emission is powered by the neutron star's rotating magnetic field. This evolutionary model is supported by the detection of millisecond X-ray pulsations from several accreting neutron stars and also by the evidence for a past accretion disc in a rotation-powered millisecond pulsar. It has been proposed that a rotation-powered pulsar may temporarily switch on during periods of low mass inflow in some such systems. Only indirect evidence for this transition has hitherto been observed. Here we report observations of accretion-powered, millisecond X-ray pulsations from a neutron star previously seen as a rotation-powered radio pulsar. Within a few days after a month-long X-ray outburst, radio pulses were again detected. This not only shows the evolutionary link between accretion and rotation-powered millisecond pulsars, but also that some systems can swing between the two states on very short timescales.Comment: 43 pages, 9 figures, 4 table. Published by Nature on 26 Sep 2013. Includes Supplementary information. Minor differences with published version may exis
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