2,432 research outputs found

    Femtosecond laser-induced microstructures on diamond for microfluidic sensing device applications

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    This paper reported a three-dimensional microfluidic channel structure, which was fabricated by Yb:YAG 1026?nm femtosecond laser irradiation on a single-crystalline diamond substrate. The femtosecond laser irradiation energy level was optimized at 100?kHz repetition rate with a sub-500 femtosecond pulse duration. The morphology and topography of the microfluidic channel were characterized by a scanning electron microscope and an atomic force microscope. Raman spectroscopy indicated that the irradiated area was covered by graphitic materials. By comparing the cross-sectional profiles before/after removing the graphitic materials, it could be deduced that the microfluidic channel has an average depth of ~410?nm with periodical ripples perpendicular to the irradiation direction. This work proves the feasibility of using ultra-fast laser inscription technology to fabricate microfluidic channels on biocompatible diamond substrates, which offers a great potential for biomedical sensing applications

    Aemulus ν\nu: Precise Predictions for Matter and Biased Tracer Power Spectra in the Presence of Neutrinos

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    We present the Aemulus ν\nu simulations: a suite of 150 (1.05h−1Gpc)3(1.05 h^{-1}\rm Gpc)^3 NN-body simulations with a mass resolution of 3.51×1010Ωcb0.3 h−1M⊙3.51\times 10^{10} \frac{\Omega_{cb}}{0.3} ~ h^{-1} M_{\odot} in a wνw\nuCDM cosmological parameter space. The simulations have been explicitly designed to span a broad range in σ8\sigma_8 to facilitate investigations of tension between large scale structure and cosmic microwave background cosmological probes. Neutrinos are treated as a second particle species to ensure accuracy to 0.5 eV0.5\, \rm eV, the maximum neutrino mass that we have simulated. By employing Zel'dovich control variates, we increase the effective volume of our simulations by factors of 10−10510-10^5 depending on the statistic in question. As a first application of these simulations, we build new hybrid effective field theory and matter power spectrum surrogate models, demonstrating that they achieve ≤1%\le 1\% accuracy for k≤1 h Mpc−1k\le 1\, h\,\rm Mpc^{-1} and 0≤z≤30\le z \le 3, and ≤2%\le 2\% accuracy for k≤4 h Mpc−1k\le 4\, h\,\rm Mpc^{-1} for the matter power spectrum. We publicly release the trained surrogate models, and estimates of the surrogate model errors in the hope that they will be broadly applicable to a range of cosmological analyses for many years to come.Comment: 37 pages, 15 figures, matching version accepted by JCA

    Contribution of the gp120 V3 loop to envelope glycoprotein trimer stability in primate immunodeficiency viruses

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    The V3 loop of the human immunodeficiency virus type 1 (HIV-1) gp120 exterior envelope glycoprotein (Env) becomes exposed after CD4 binding and contacts the coreceptor to mediate viral entry. Prior to CD4 engagement, a hydrophobic patch located at the tip of the V3 loop stabilizes the non-covalent association of gp120 with the Env trimer of HIV-1 subtype B strains. Here, we show that this conserved hydrophobic patch (amino acid residues 307, 309 and 317) contributes to gp120-trimer association in HIV-1 subtype C, HIV-2 and SIV. Changes that reduced the hydrophobicity of these V3 residues resulted in increased gp120 shedding and decreased Envmediated cell-cell fusion and virus entry in the different primate immunodeficiency viruses tested. Thus, the hydrophobic patch is an evolutionarily conserved element in the tip of the gp120 V3 loop that plays an essential role in maintaining the stability of the pre-triggered Env trimer in diverse primate immunodeficiency viruses

    An increase in surface hydrophobicity mediates chaperone activity in N-chlorinated RidA

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    Under physiological conditions, Escherichia coli RidA is an enamine/imine deaminase, which promotes the release of ammonia from reactive enamine/imine intermediates. However, when modified by hypochlorous acid (HOCl), it turns into a potent chaperone-like holdase that can effectively protect E. coli\u27s proteome during oxidative stress. However, it is unknown, which residues need to be chlorinated for activation. Here, we employ a combination of LC-MS/MS analysis, a chemo-proteomic approach, and a mutagenesis study to identify residues responsible for RidA\u27s chaperone-like function. Through LC-MS/MS of digested RidAHOCl, we obtained direct evidence of the chlorination of one arginine residue. To overcome the instability of the N-chloramine modification, we established a chemoproteomic approach using 5-(dimethylamino) naphthalene-1-sulfinic acid (DANSO2_{2}H) as a probe to label N-chlorinated lysines. Using this probe, we were able to detect the N-chlorination of six additional lysine residues. Moreover, using a mutagenesis study to genetically probe the role of single arginine and lysine residues, we found that the removal of arginines R105 and/or R128 led to a substantial reduction of RidAHOCl2˘7s_{HOCl\u27s} chaperone activity. These results, together with structural analysis, confirm that the chaperone activity of RidA is concomitant with the loss of positive charges on the protein surface, leading to an increased overall protein hydrophobicity. Molecular modelling of RidAHOCl and the rational design of a RidA variant that shows chaperone activity even in the absence of HOCl further supports our hypothesis. Our data provide a molecular mechanism for HOCl-mediated chaperone activity found in RidA and a growing number of other HOCl-activated chaperones

    Post-starburst galaxies in SDSS-IV MaNGA

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    Funding: European Research Council via the award of a starting grant (SEDMorph; P.I. V. Wild) (VW, KR).Post-starburst galaxies, identified by their unusually strong Balmer absorption lines and weaker than average emission lines, have traditionally been selected based on their central stellar populations. Here we identify 360 galaxies with post-starburst regions from the MaNGA integral field survey and classify these galaxies into three types: 31 galaxies with central post-starburst regions (CPSB), 37 galaxies with off-center ring-like post-starburst regions (RPSB) and 292 galaxies with irregular post-starburst regions (IPSB). Focussing on the CPSB and RPSB samples, and comparing their radial gradients in Dn4000, HδA and W(Hα) to control samples, we find that while the CPSBs have suppressed star formation throughout their bulge and disk, and clear evidence of rapid decline of star formation in the central regions, the RPSBs only show clear evidence of recently rapidly suppressed star formation in their outer regions and an ongoing central starburst. The radial profiles in mass-weighted age and stellar v/σ indicate that CPSBs and RPSBs are not simply different evolutionary stages of the same event, rather that CPSB galaxies are caused by a significant disruptive event, while RPSB galaxies are caused by disruption of gas fuelling to the outer regions. Compared to the control samples, both CPSB and RPSB galaxies show a higher fraction of interactions/mergers, misaligned gas or bars that might be the cause of the gas inflows and subsequent quenching.PostprintPeer reviewe

    Haemophilus parasuis molecular serotyping assay

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    Haemophilus parasuis causes Glässer's disease and pneumonia in pigs. Indirect hemagglutination (IHA) is typically used to serotype this bacterium, distinguishing 15 serovars with some nontypeable isolates. The capsule loci of the 15 reference strains have been annotated, and significant genetic variation was identified between serovars, with the exception of serovars 5 and 12. A capsule locus and in silico serovar were identified for all but two nontypeable isolates in our collection of >200 isolates. Here, we describe the development of a multiplex PCR, based on variation within the capsule loci of the 15 serovars of H. parasuis, for rapid molecular serotyping. The multiplex PCR (mPCR) distinguished between all previously described serovars except 5 and 12, which were detected by the same pair of primers. The detection limit of the mPCR was 4.29 × 10(5) ng/μl bacterial genomic DNA, and high specificity was indicated by the absence of reactivity against closely related commensal Pasteurellaceae and other bacterial pathogens of pigs. A subset of 150 isolates from a previously sequenced H. parasuis collection was used to validate the mPCR with 100% accuracy compared to the in silico results. In addition, the two in silico-nontypeable isolates were typeable using the mPCR. A further 84 isolates were analyzed by mPCR and compared to the IHA serotyping results with 90% concordance (excluding those that were nontypeable by IHA). The mPCR was faster, more sensitive, and more specific than IHA, enabling the differentiation of 14 of the 15 serovars of H. parasuis.This work was supported by a BPEX PhD studentship and a Longer and Larger (LoLa) grant from the Biotechnology and Biological Sciences Research Council (grant numbers BB/G020744/1, BB/G019177/1, BB/G019274/1 and BB/G003203/1), the UK Department for Environment, Food and Rural Affairs and Zoetis, awarded to the Bacterial Respiratory Diseases of Pigs-1 Technology (BRaDP1T) consortium. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.This is the author accepted manuscript. The final version is available from American Society for Microbiology via http://dx.doi.org/10.1128/JCM.01991-1

    Economic evaluation of the introduction of rotavirus vaccine in Hong Kong.

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    Background Rotavirus is a common cause of severe gastroenteritis in young children in Hong Kong (HK) with a high economic burden. This study aimed to evaluate the cost-effectiveness of introducing rotavirus vaccination into the HK Government's Childhood Immunisation Programme (CIP) and to include the potential protective effect of the vaccine against seizures. Methods A decision-support model was customised to estimate the potential impact, cost-effectiveness and benefit-risk of rotavirus vaccination in children below 5 years over the period 2020-2029 in HK. Two doses of Rotarix® and three doses of RotaTeq® were each compared to no vaccination. Rotavirus treatment costs were calculated from a governmental health sector perspective (i.e., costs of public sector treatment) and an overall health sector perspective (both governmental and patient, i.e., costs of public sector treatment, private sector treatment, transport and diapers). We ran probabilistic and deterministic uncertainty analyses. Results Introduction of rotavirus vaccination in HK could prevent 49,000 (95% uncertainty interval: ~44,000-54,000) hospitalisations of rotavirus gastroenteritis and seizures and result in ~50 (95% uncertainty interval: ~25-85) intussusception hospitalisations, over the period 2020-2029 (a benefit-risk ratio of ~1000:1), compared to a scenario with no public or private sector vaccine use. The discounted vaccination cost would be US51−57millionovertheperiod2020−2029basedonper−coursepricesofUS51-57 million over the period 2020-2029 based on per-course prices of US72 (Rotarix®) or US78(RotaTeq®),butthiswouldbeoffsetbydiscountedtreatmentcostsavingsofUS78 (RotaTeq®), but this would be offset by discounted treatment cost savings of US70 million (government) and US$127 million (governmental and patient health sector). There was a greater than 94% probability that the vaccine could be cost-saving irrespective of the vaccine product or perspective considered. All deterministic 'what-if' scenarios were cost-saving from an overall health sector perspective (governmental and patient). Conclusions Rotavirus vaccination is likely to be cost-saving and have a favourable benefit-risk profile in HK. Based on the assumptions made, our analysis supports its introduction into CIP
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