267 research outputs found

    Maxwell-like Lagrangians for higher spins

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    We show how implementing invariance under divergence-free gauge transformations leads to a remarkably simple Lagrangian description of massless bosons of any spin. Our construction covers both flat and (A)dS backgrounds and extends to tensors of arbitrary mixed-symmetry type. Irreducible and traceless fields produce single-particle actions, while whenever trace constraints can be dispensed with the resulting Lagrangians display the same reducible, multi-particle spectra as those emerging from the tensionless limit of free open-string field theory. For all explored options the corresponding kinetic operators take essentially the same form as in the spin-one, Maxwell case.Comment: 77 pages, revised version. Erroneous interpretation and proof of the gauge-fixing procedure for mixed-symmetry fields corrected. As a consequence, the mixed-symmetry, one-particle Lagrangians are to be complemented with conditions on the divergences of the fields; all other conclusions unchanged. Additional minor changes including references added. To appear in JHE

    Microparticle-mediated transfer of the viral receptors CAR and CD46, and the CFTR channel in a CHO cell model confers new functions to target cells

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    Cell microparticles (MPs) released in the extracellular milieu can embark plasma membrane and intracellular components which are specific of their cellular origin, and transfer them to target cells. The MP-mediated, cell-to-cell transfer of three human membrane glycoproteins of different degrees of complexity was investigated in the present study, using a CHO cell model system. We first tested the delivery of CAR and CD46, two monospanins which act as adenovirus receptors, to target CHO cells. CHO cells lack CAR and CD46, high affinity receptors for human adenovirus serotype 5 (HAdV5), and serotype 35 (HAdV35), respectively. We found that MPs derived from CHO cells (MP-donor cells) constitutively expressing CAR (MP-CAR) or CD46 (MP-CD46) were able to transfer CAR and CD46 to target CHO cells, and conferred selective permissiveness to HAdV5 and HAdV35. In addition, target CHO cells incubated with MP-CD46 acquired the CD46-associated function in complement regulation. We also explored the MP-mediated delivery of a dodecaspanin membrane glycoprotein, the CFTR to target CHO cells. CFTR functions as a chloride channel in human cells and is implicated in the genetic disease cystic fibrosis. Target CHO cells incubated with MPs produced by CHO cells constitutively expressing GFP-tagged CFTR (MP-GFP-CFTR) were found to gain a new cellular function, the chloride channel activity associated to CFTR. Time-course analysis of the appearance of GFP-CFTR in target cells suggested that MPs could achieve the delivery of CFTR to target cells via two mechanisms: the transfer of mature, membrane-inserted CFTR glycoprotein, and the transfer of CFTR-encoding mRNA. These results confirmed that cell-derived MPs represent a new class of promising therapeutic vehicles for the delivery of bioactive macromolecules, proteins or mRNAs, the latter exerting the desired therapeutic effect in target cells via de novo synthesis of their encoded proteins

    Cold gas accretion in galaxies

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    Evidence for the accretion of cold gas in galaxies has been rapidly accumulating in the past years. HI observations of galaxies and their environment have brought to light new facts and phenomena which are evidence of ongoing or recent accretion: 1) A large number of galaxies are accompanied by gas-rich dwarfs or are surrounded by HI cloud complexes, tails and filaments. It may be regarded as direct evidence of cold gas accretion in the local universe. It is probably the same kind of phenomenon of material infall as the stellar streams observed in the halos of our galaxy and M31. 2) Considerable amounts of extra-planar HI have been found in nearby spiral galaxies. While a large fraction of this gas is produced by galactic fountains, it is likely that a part of it is of extragalactic origin. 3) Spirals are known to have extended and warped outer layers of HI. It is not clear how these have formed, and how and for how long the warps can be sustained. Gas infall has been proposed as the origin. 4) The majority of galactic disks are lopsided in their morphology as well as in their kinematics. Also here recent accretion has been advocated as a possible cause. In our view, accretion takes place both through the arrival and merging of gas-rich satellites and through gas infall from the intergalactic medium (IGM). The infall may have observable effects on the disk such as bursts of star formation and lopsidedness. We infer a mean ``visible'' accretion rate of cold gas in galaxies of at least 0.2 Msol/yr. In order to reach the accretion rates needed to sustain the observed star formation (~1 Msol/yr), additional infall of large amounts of gas from the IGM seems to be required.Comment: To appear in Astronomy & Astrophysics Reviews. 34 pages. Full-resolution version available at http://www.astron.nl/~oosterlo/accretionRevie

    Planck intermediate results. XLI. A map of lensing-induced B-modes

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    The secondary cosmic microwave background (CMB) BB-modes stem from the post-decoupling distortion of the polarization EE-modes due to the gravitational lensing effect of large-scale structures. These lensing-induced BB-modes constitute both a valuable probe of the dark matter distribution and an important contaminant for the extraction of the primary CMB BB-modes from inflation. Planck provides accurate nearly all-sky measurements of both the polarization EE-modes and the integrated mass distribution via the reconstruction of the CMB lensing potential. By combining these two data products, we have produced an all-sky template map of the lensing-induced BB-modes using a real-space algorithm that minimizes the impact of sky masks. The cross-correlation of this template with an observed (primordial and secondary) BB-mode map can be used to measure the lensing BB-mode power spectrum at multipoles up to 20002000. In particular, when cross-correlating with the BB-mode contribution directly derived from the Planck polarization maps, we obtain lensing-induced BB-mode power spectrum measurement at a significance level of 12σ12\,\sigma, which agrees with the theoretical expectation derived from the Planck best-fit Λ\LambdaCDM model. This unique nearly all-sky secondary BB-mode template, which includes the lensing-induced information from intermediate to small (10100010\lesssim \ell\lesssim 1000) angular scales, is delivered as part of the Planck 2015 public data release. It will be particularly useful for experiments searching for primordial BB-modes, such as BICEP2/Keck Array or LiteBIRD, since it will enable an estimate to be made of the lensing-induced contribution to the measured total CMB BB-modes.Comment: 20 pages, 12 figures; Accepted for publication in A&A; The B-mode map is part of the PR2-2015 Cosmology Products; available as Lensing Products in the Planck Legacy Archive http://pla.esac.esa.int/pla/#cosmology; and described in the 'Explanatory Supplement' https://wiki.cosmos.esa.int/planckpla2015/index.php/Specially_processed_maps#2015_Lensing-induced_B-mode_ma

    A Trial of the Efficacy, Safety and Impact on Drug Resistance of Four Drug Regimens for Seasonal Intermittent Preventive Treatment for Malaria in Senegalese Children

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    UNLABELLED: In the Sahel, most malaria deaths occur among children 1-4 years old during a short transmission season. A trial of seasonal intermittent preventive treatment (IPT) with sulfadoxine-pyrimethamine (SP) and a single dose of artesunate (AS) showed an 86% reduction in the incidence of malaria in Senegal but this may not be the optimum regimen. We compared this regimen with three alternatives. METHODS: 2102 children aged 6-59 months received either one dose of SP plus one dose of AS (SP+1AS) (the previous regimen), one dose of SP plus 3 daily doses of AS (SP+3AS), one dose of SP plus three daily doses of amodiaquine (AQ) (SP+3AQ) or 3 daily doses of AQ and AS (3AQ+3AS). Treatments were given once a month on three occasions during the malaria transmission season. The primary end point was incidence of clinical malaria. Secondary end-points were incidence of adverse events, mean haemoglobin concentration and prevalence of parasites carrying markers of resistance to SP. FINDINGS: The incidence of malaria, and the prevalence of parasitaemia at the end of the transmission season, were lowest in the group that received SP+3AQ: 10% of children in the group that received SP+1AS had malaria, compared to 9% in the SP+3AS group (hazard ratio HR 0.90, 95%CI 0.60, 1.36); 11% in the 3AQ+3AS group, HR 1.1 (0.76-1.7); and 5% in the SP+3AQ group, HR 0.50 (0.30-0.81). Mutations associated with resistance to SP were present in almost all parasites detected at the end of the transmission season, but the prevalence of Plasmodium falciparum was very low in the SP+3AQ group. CONCLUSIONS: Monthly treatment with SP+3AQ is a highly effective regimen for seasonal IPT. Choice of this regimen would minimise the spread of drug resistance and allow artemisinins to be reserved for the treatment of acute clinical malaria

    Circulating CD62E+ Microparticles and Cardiovascular Outcomes

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    BACKGROUND: Activated endothelial cells release plasma membrane submicron vesicles expressing CD62E (E-selectin) into blood, known as endothelial microparticles (EMPs). We studied whether the levels of endothelial microparticles expressing CD62E(+), CD31(+)/Annexin-V(+), or CD31(+)/CD42(-) predict cardiovascular outcomes in patients with stroke history. METHODS/PRINCIPAL FINDINGS: Patients with stroke history at least 3 months prior to enrolment were recruited. Peripheral blood EMP levels were measured by flow cytometry. Major cardiovascular events and death were monitored for 36 months. Three hundred patients were enrolled, of which 298 completed the study according to protocol. Major cardiovascular events occurred in 29 patients (9.7%). Nine patients died, five from cardiovascular causes. Cumulative event-free survival rates were lower in patients with high levels of CD62E(+) microparticles. Multivariate Cox regression analysis adjusted for cardiovascular risk factors, medications and stroke etiologic groups showed an association between a high CD62E(+) microparticle level and a risk of major cardiovascular events and hospitalization. Levels of other kinds of EMPs expressing CD31(+)/Annexin-V(+) or CD31(+)/CD42(-) markers were not predictive of cardiovascular outcomes. CONCLUSION: A high level of CD62E(+) microparticles is associated with cardiovascular events in patients with stroke history, suggesting that the systemic endothelial activation increases the risk for cardiovascular morbidities

    Planck 2015 results: I. Overview of products and scientific results

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    The European Space Agency's Planck satellite, which is dedicated to studying the early Universe and its subsequent evolution, was launched on 14 May 2009. It scanned the microwave and submillimetre sky continuously between 12 August 2009 and 23 October 2013. In February 2015, ESA and the Planck Collaboration released the second set of cosmology products based ondata from the entire Planck mission, including both temperature and polarization, along with a set of scientific and technical papers and a web-based explanatory supplement. This paper gives an overview of the main characteristics of the data and the data products in the release, as well as the associated cosmological and astrophysical science results and papers. The data products include maps of the cosmic microwave background (CMB), the thermal Sunyaev-Zeldovich effect, diffuse foregrounds in temperature and polarization, catalogues of compact Galactic and extragalactic sources (including separate catalogues of Sunyaev-Zeldovich clusters and Galactic cold clumps), and extensive simulations of signals and noise used in assessing uncertainties and the performance of the analysis methods. The likelihood code used to assess cosmological models against the Planck data is described, along with a CMB lensing likelihood. Scientific results include cosmological parameters derived from CMB power spectra, gravitational lensing, and cluster counts, as well as constraints on inflation, non-Gaussianity, primordial magnetic fields, dark energy, and modified gravity, and new results on low-frequency Galactic foregrounds

    High Affinity Antigen Recognition of the Dual Specific Variants of Herceptin Is Entropy-Driven in Spite of Structural Plasticity

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    The antigen-binding site of Herceptin, an anti-human Epidermal Growth Factor Receptor 2 (HER2) antibody, was engineered to add a second specificity toward Vascular Endothelial Growth Factor (VEGF) to create a high affinity two-in-one antibody bH1. Crystal structures of bH1 in complex with either antigen showed that, in comparison to Herceptin, this antibody exhibited greater conformational variability, also called “structural plasticity”. Here, we analyzed the biophysical and thermodynamic properties of the dual specific variants of Herceptin to understand how a single antibody binds two unrelated protein antigens. We showed that while bH1 and the affinity-improved bH1-44, in particular, maintained many properties of Herceptin including binding affinity, kinetics and the use of residues for antigen recognition, they differed in the binding thermodynamics. The interactions of bH1 and its variants with both antigens were characterized by large favorable entropy changes whereas the Herceptin/HER2 interaction involved a large favorable enthalpy change. By dissecting the total entropy change and the energy barrier for dual interaction, we determined that the significant structural plasticity of the bH1 antibodies demanded by the dual specificity did not translate into the expected increase of entropic penalty relative to Herceptin. Clearly, dual antigen recognition of the Herceptin variants involves divergent antibody conformations of nearly equivalent energetic states. Hence, increasing the structural plasticity of an antigen-binding site without increasing the entropic cost may play a role for antibodies to evolve multi-specificity. Our report represents the first comprehensive biophysical analysis of a high affinity dual specific antibody binding two unrelated protein antigens, furthering our understanding of the thermodynamics that drive the vast antigen recognition capacity of the antibody repertoire

    ABJ theory in the higher spin limit

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    This article is distributed under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits any use, distribution and reproduction in any medium, provided the original author(s) and source are creditedArticle funded by SCOAP3 .Article funded by SCOAP3 .The work of SH was supported in part by the National Research Foundation of South Africa and DSTNRF Centre of Excellence in Mathematical and Statistical Sciences (CoE-MaSS). Opinions expressed and conclusions arrived at are those of the author and are not necessarily to be attributed to the NRF or the CoE-MaSS. The work of KO was supported in part by JSPS Grant-in-Aid for Young Scientists (B) 23740178. MS is grateful to the Weizmann Institute for the stimulating environment at the “Black Holes and Quantum Information” workshop. The work of MS was supported in part by Grant-in-Aid for Young Scientists (B) 24740159 from the Japan Society for the Promotion of Science (JSPS)
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