444 research outputs found

    Evaluation of a new, perforated heat flux plate design

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    Accurate measurement of heat flux is essential to optimize structural and process design and to improve understanding of energy transfer in natural systems. Laboratory and field experiments evaluated the performance of a new, perforated heat flux plate designed to reduce flow distortion for environmental applications. Laboratory tests involving dry and saturated sand showed that performance of the new CAPTEC plate is comparable to a solid, standard REBS plate. Very low thermal gradients may have however led to poor performance of the CAPTEC plate in saturated sand. Water infiltration and redistribution experiments using clayey and sandy soils showed an apparent reduced disruption of liquid water and vapour in the soil surrounding the CAPTEC plate as compared to solid Hukseflux and standard REBS plates. Surface area of REBS plate, though smaller than that of CAPTEC, did not lead to any significantly improved evaporation, due to perforations on CAPTEC plate. Field tests in a loam soil indicated that the CAPTEC plates were durable and produced daily total flux values within ~ 0.15 MJ m− 2 of independent estimates

    A role for core planar polarity proteins in cell contact-mediated orientation of planar cell division across the mammalian embryonic skin

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    Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2017. Supplementary information accompanies this paper at doi:10.1038/s41598-017-01971-2.The question of how cell division orientation is determined is fundamentally important for understanding tissue and organ shape in both healthy or disease conditions. Here we provide evidence for cell contact-dependent orientation of planar cell division in the mammalian embryonic skin. We propose a model where the core planar polarity proteins Celsr1 and Frizzled-6 (Fz6) communicate the long axis orientation of interphase basal cells to neighbouring basal mitoses so that they align their horizontal division plane along the same axis. The underlying mechanism requires a direct, cell surface, planar polarised cue, which we posit depends upon variant post-translational forms of Celsr1 protein coupled to Fz6. Our hypothesis has parallels with contact-mediated division orientation in early C. elegans embryos suggesting functional conservation between the adhesion-GPCRs Celsr1 and Latrophilin-1. We propose that linking planar cell division plane with interphase neighbour long axis geometry reinforces axial bias in skin spreading around the mouse embryo body.Peer reviewe

    Durability of Stavudine, Lamivudine and Nevirapine among Advanced HIV-1 Infected Patients with/without Prior Co-administration of Rifampicin: A 144-week Prospective Study

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    <p>Abstract</p> <p>Background</p> <p>To date, data on the durability of a regimen of stavudine, lamivudine and nevirapine are very limited, particularly from the resource-limited settings.</p> <p>Methods</p> <p>A prospective cohort study was conducted among 140 antiretroviral-naïve patients who were enrolled to initiate d4T, 3TC and NVP between November 2004 and March 2005. The objectives were to determine immunological and virological responses after 144 weeks of antiretroviral therapy. Seventy patients with tuberculosis also received rifampicin during the early period of antiviral treatment (TB group).</p> <p>Results</p> <p>Of all, median (IQR) baseline CD4 cell count was 31 (14–79) cells/mm<sup>3</sup>; median (IQR) baseline HIV-1 RNA was 433,500 (169,000–750,000) copies/mL. The average body weight was 55 kilograms. By intention-to-treat analysis at 144 weeks, the overall percentage of patients who achieved plasma HIV-1 RNA <50 copies/mL was 59.3% (83/140). In subgroup analysis, 61.4% (43/70) patients in TB group and 57.1% (40/70) patients in control group achieved plasma HIV-1 RNA <50 copies/mL (RR = 1.194, 95%CI = 0.608–2.346, <it>P </it>= 0.731). Eight (5.8%) patients discontinued d4T due to neuropathy and/or symptomatic lactic acidosis.</p> <p>Conclusion</p> <p>The overall durability and efficacy of antiviral response of d4T, 3TC and NVP are satisfied and they are not different between HIV-1 infected patients with and without co-administration of rifampicin due to tuberculosis. However, stavudine-related adverse effects are concerns.</p> <p>Trial registration</p> <p>ClinicalTrials.gov Identifier NCT00703898</p

    Exosomes released by EBV-infected nasopharyngeal carcinoma cells convey the viral Latent Membrane Protein 1 and the immunomodulatory protein galectin 9

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    BACKGROUND: Nasopharyngeal carcinomas (NPC) are consistently associated with the Epstein-Barr virus (EBV). Their malignant epithelial cells contain the viral genome and express several antigenic viral proteins. However, the mechanisms of immune escape in NPCs are still poorly understood. EBV-transformed B-cells have been reported to release exosomes carrying the EBV-encoded latent membrane protein 1 (LMP1) which has T-cell inhibitory activity. Although this report suggested that NPC cells could also produce exosomes carrying immunosuppressive proteins, this hypothesis has remained so far untested. METHODS: Malignant epithelial cells derived from NPC xenografts – LMP1-positive (C15) or negative (C17) – were used to prepare conditioned culture medium. Various microparticles and vesicles released in the culture medium were collected and fractionated by differential centrifugation. Exosomes collected in the last centrifugation step were further purified by immunomagnetic capture on beads carrying antibody directed to HLA class II molecules. Purified exosomes were visualized by electron microscopy and analysed by western blotting. The T-cell inhibitory activities of recombinant LMP1 and galectin 9 were assessed on peripheral blood mononuclear cells activated by CD3/CD28 cross-linking. RESULTS: HLA-class II-positive exosomes purified from C15 and C17 cell supernatants were containing either LMP1 and galectin 9 (C15) or galectin 9 only (C17). Recombinant LMP1 induced a strong inhibition of T-cell proliferation (IC50 = 0.17 nM). In contrast recombinant galectin 9 had a weaker inhibitory effect (IC50 = 46 nM) with no synergy with LMP1. CONCLUSION: This study provides the proof of concept that NPC cells can release HLA class-II positive exosomes containing galectin 9 and/or LMP1. It confirms that the LMP1 molecule has intrinsic T-cell inhibitory activity. These findings will encourage investigations of tumor exosomes in the blood of NPC patients and assessment of their effects on various types of target cells

    Autophagy and Exosomes in the Aged Retinal Pigment Epithelium: Possible Relevance to Drusen Formation and Age-Related Macular Degeneration

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    Age-related macular degeneration (AMD) is a major cause of loss of central vision in the elderly. The formation of drusen, an extracellular, amorphous deposit of material on Bruch's membrane in the macula of the retina, occurs early in the course of the disease. Although some of the molecular components of drusen are known, there is no understanding of the cell biology that leads to the formation of drusen. We have previously demonstrated increased mitochondrial DNA (mtDNA) damage and decreased DNA repair enzyme capabilities in the rodent RPE/choroid with age. In this study, we found that drusen in AMD donor eyes contain markers for autophagy and exosomes. Furthermore, these markers are also found in the region of Bruch's membrane in old mice. By in vitro modeling increased mtDNA damage induced by rotenone, an inhibitor of mitochondrial complex I, in the RPE, we found that the phagocytic activity was not altered but that there were: 1) increased autophagic markers, 2) decreased lysosomal activity, 3) increased exocytotic activity and 4) release of chemoattractants. Exosomes released by the stressed RPE are coated with complement and can bind complement factor H, mutations of which are associated with AMD. We speculate that increased autophagy and the release of intracellular proteins via exosomes by the aged RPE may contribute to the formation of drusen. Molecular and cellular changes in the old RPE may underlie susceptibility to genetic mutations that are found in AMD patients and may be associated with the pathogenesis of AMD in the elderly

    Dependence of the ttˉt\bar{t} production cross section on the transverse momentum of the top quark

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    We present a measurement of the differential cross section for ttˉt\bar{t} events produced in ppˉp\bar{p} collisions at s=1.96\sqrt{s}=1.96 TeV as a function of the transverse momentum (pTp_T) of the top quark. The selected events contain a high-pTp_T lepton (ℓ\ell), four or more jets, and a large imbalance in pTp_T, and correspond to 1 fb−1{}^{-1} of integrated luminosity recorded with the D0 detector. Each event must have at least one candidate for a bb jet. Objects in the event are associated through a constrained kinematic fit to the ttˉ→WbWbˉ→ℓΜbqqˉâ€Čbˉt\bar{t}\to WbW\bar{b} \to \ell\nu b q\bar{q}'\bar{b} process. Results from next-to-leading-order perturbative QCD calculations agree with the measured differential cross section. Comparisons are also provided to predictions from Monte Carlo event generators using QCD calculations at different levels of precision.Comment: 8 pages, 6 figures, 4 tables, updated to reflect the published versio

    A search for charged massive long-lived particles

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    We report on a search for charged massive long-lived particles (CMLLPs), based on 5.2 fb−1^{-1} of integrated luminosity collected with the D0 detector at the Fermilab Tevatron ppˉp\bar{p} collider. We search for events in which one or more particles are reconstructed as muons but have speed and ionization energy loss (dE/dx)(dE/dx) inconsistent with muons produced in beam collisions. CMLLPs are predicted in several theories of physics beyond the standard model. We exclude pair-produced long-lived gaugino-like charginos below 267 GeV and higgsino-like charginos below 217 GeV at 95% C.L., as well as long-lived scalar top quarks with mass below 285 GeV.Comment: submitted to Phys. Rev. Letter

    Search for WHWH associated production in ppˉp \bar{p} collisions at s=1.96 TeV\sqrt{s}=1.96\,{\rm TeV}

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    This report describes a search for associated production of WW and Higgs bosons based on data corresponding to an integrated luminosity of L\cal{L}≈5.3fb−1 \approx 5.3 \rm fb^{-1} collected with the D0 detector at the Fermilab Tevatron ppˉp\bar{p} Collider. Events containing a W→ℓΜW\rightarrow \ell \nu candidate (with ℓ\ell corresponding to ee or ÎŒ\mu) are selected in association with two or three reconstructed jets. One or two of the jets are required to be consistent with having evolved from a bb quark. A multivariate discriminant technique is used to improve the separation of signal and backgrounds. Expected and observed upper limits are obtained for the product of the WHWH production cross section and branching ratios and reported in terms of ratios relative to the prediction of the standard model as a function of the mass of the Higgs boson (MHM_{H}). The observed and expected 95% C.L. upper limits obtained for an assumed MH=115GeVM_{H}=115 \rm GeV are, respectively, factors of 4.5 and 4.8 larger than the value predicted by the standard model.Comment: 25 pages, 14 figure

    Zgamma production and limits on anomalous ZZgamma and Zgammagamma couplings in ppbar collisions at sqrt(s)=1.96 TeV

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    We present a measurement of ppbar->Zgamma->ll+gamma (l = e, mu) production with a data sample corresponding to an integrated luminosity of 6.2 fb^{-1} collected by the D0 detector at the Fermilab Tevatron ppbar Collider. The results of the electron and muon channels are combined, and we measure the total production cross section and the differential cross section dsigma/dp_T^gamma, where p_T^gamma is the momentum of the photon in the plane transverse to the beamline. The results obtained are consistent with the standard model predictions from next-to-leading order calculations. We use the transverse momentum spectrum of the photon to place limits on anomalous ZZgamma and Zgammagamma couplings

    Search for first generation leptoquark pair production in the electron + missing energy + jets final state

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    We present a search for the pair production of first generation scalar leptoquarks (LQ) in data corresponding to an integrated luminosity of 5.4 fb−1^{-1} collected with the D0 detector at the Fermilab Tevatron Collider in ppbar collisions at s=1.96\sqrt{s}=1.96 TeV. In the channel LQLQˉ→eÎœeqqâ€ČLQ \bar{LQ} \rightarrow e\nu_e qq', where q, q' are u or d quarks, no significant excess of data over background is observed, and we set a 95% C.L. lower limit of 326 GeV on the leptoquark mass, assuming equal probabilities of leptoquark decays to eq and Îœeqâ€Č\nu_e q'.Comment: 7 pages, 6 figures, submitted to PRD-R
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