An asteroseismic membership study of the red giants in three open clusters observed by Kepler: NGC6791, NGC6819, and NGC6811

Studying star clusters offers significant advances in stellar astrophysics due to the combined power of having many stars with essentially the same distance, age, and initial composition. This makes clusters excellent test benches for verification of stellar evolution theory. To fully exploit this potential, it is vital that the star sample is uncontaminated by stars that are not members of the cluster. Techniques for determining cluster membership therefore play a key role in the investigation of clusters. We present results on three clusters in the Kepler field of view based on a newly established technique that uses asteroseismology to identify fore- or background stars in the field, which demonstrates advantages over classical methods such as kinematic and photometry measurements. Four previously identified seismic non-members in NGC6819 are confirmed in this study, and three additional non-members are found -- two in NGC6819 and one in NGC6791. We further highlight which stars are, or might be, affected by blending, which needs to be taken into account when analysing these Kepler data.Comment: 12 pages, 9 figures, 5 tables, accepted by Ap

Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits

Background: The trimeric envelope glycoproteins (Env) on the surface of HIV-1 virions are the targets for neutralizing antibodies (NAbs). No candidate HIV-1 immunogen has yet induced potent, broadly active NAbs (bNAbs). Part of the explanation may be that previously tested Env proteins inadequately mimic the functional, native Env complex. Trimerization and the proteolytic processing of Env precursors into gp120 and gp41 profoundly alter antigenicity, but soluble cleaved trimers are too unstable to serve as immunogens. By introducing stabilizing mutations (SOSIP), we constructed soluble, cleaved Env trimers derived from the HIV-1 subtype A isolate BG505 that resemble native Env spikes on virions both structurally and antigenically. Results: We used surface plasmon resonance (SPR) to quantify antibody binding to different forms of BG505 Env: the proteolytically cleaved SOSIP.664 trimers, cleaved gp120-gp41ECTO protomers, and gp120 monomers. Non-NAbs to the CD4-binding site bound only marginally to the trimers but equally well to gp120-gp41ECTO protomers and gp120 monomers, whereas the bNAb VRC01, directed to the CD4bs, bound to all three forms. In contrast, bNAbs to V1V2 glycan-dependent epitopes bound preferentially (PG9 and PG16) or exclusively (PGT145) to trimers. We also explored the antigenic consequences of three different features of SOSIP.664 gp140 trimers: the engineered inter-subunit disulfide bond, the trimer-stabilizing I559P change in gp41ECTO, and proteolytic cleavage at the gp120-gp41ECTO junction. Each of these three features incrementally promoted native-like trimer antigenicity. We compared Fab and IgG versions of bNAbs and validated a bivalent model of IgG binding. The NAbs showed widely divergent binding kinetics and degrees of binding to native-like BG505 SOSIP.664. High off-rate constants and low stoichiometric estimates of NAb binding were associated with large amounts of residual infectivity after NAb neutralization of the corresponding BG505.T332N pseudovirus. Conclusions: The antigenicity and structural integrity of cleaved BG505 SOSIP.664 trimers render these proteins good mimics of functional Env spikes on virions. In contrast, uncleaved gp140s antigenically resemble individual gp120-gp41ECTO protomers and gp120 monomers, but not native trimers. Although NAb binding to functional trimers may thus be both necessary and sufficient for neutralization, the kinetics and stoichiometry of the interaction influence the neutralizing efficacy of individual NAbs

The Farthest Known Supernova: Support for an Accelerating Universe and a Glimpse of the Epoch of Deceleration

We present photometric observations of an apparent Type Ia supernova (SN Ia) at a redshift of ~1.7, the farthest SN observed to date. SN 1997ff, was discovered in a repeat observation by the HST of the HDF-), and serendipitously monitored with NICMOS on HST throughout the GTO campaign. The SN type can be determined from the host galaxy type:an evolved, red elliptical lacking enough recent star formation to provide a significant population of core-collapse SNe. The class- ification is further supported by diagnostics available from the observed colors and temporal behavior of the SN, both of which match a typical SN Ia. The photo- metric record of the SN includes a dozen flux measurements in the I, J, and H bands spanning 35 days in the observed frame. The redshift derived from the SN photometry, z=1.7+/-0.1, is in excellent agreement with the redshift estimate of z=1.65+/-0.15 derived from the U_300,B_450,V_606,I_814,J_110,J_125,H_160, H_165,K_s photometry of the galaxy. Optical and near-infrared spectra of the host provide a very tentative spectroscopic redshift of 1.755. Fits to observations of the SN provide constraints for the redshift-distance relation of SNe~Ia and a powerful test of the current accelerating Universe hypothesis. The apparent SN brightness is consistent with that expected in the decelerating phase of the preferred cosmological model, Omega_M~1/3, Omega_Lambda~2/3. It is inconsistent with grey dust or simple luminosity evolution, candidate astro- physical effects which could mimic past evidence for an accelerating Universe from SNe Ia at z~0.5.We consider several sources of possible systematic error including lensing, SN misclassification, selection bias, and calibration errors. Currently, none of these effects appears likely to challenge our conclusions.Comment: Accepted to the Astrophysical Journal 38 pages, 15 figures, Pretty version available at http://icarus.stsci.edu/~stefano/ariess.tar.g

Conjugation of a Toll-Like Receptor Agonist to Glycans of an HIV Native-Like Envelope Trimer Preserves Neutralization Epitopes

Small molecule adjuvants are attractive for enhancing broad protection and durability of immune responses elicited by subunit vaccines. Covalent attachment of an adjuvant to an immunogen is particularly attractive because it simultaneously delivers both entities to antigen presenting cells resulting in more efficient immune activation. There is, however, a lack of methods to conjugate small molecule immune potentiators to viral glycoprotein immunogens without compromising epitope integrity. We describe herein a one-step enzymatic conjugation approach for the covalent attachment of small molecule adjuvants to N-linked glycans of viral glycoproteins. It involves the attachment of an immune potentiator to CMP-Neu5AcN 3 by Cu(I)-catalyzed azide-alkyne 1,3-cycloaddition followed by sialyltransferase-mediated transfer to N-glycans of a viral glycoprotein. The method was employed to modify a native-like HIV envelope trimer with a Toll-like receptor 7/8 agonist. The modification did not compromise Env-trimer recognition by several broadly neutralization antibodies. Electron microscopy confirmed structural integrity of the modified immunogen

Characterisation of the muon beams for the Muon Ionisation Cooling Experiment

A novel single-particle technique to measure emittance has been developed and used to characterise seventeen different muon beams for the Muon Ionisation Cooling Experiment (MICE). The muon beams, whose mean momenta vary from 171 to 281 MeV/c, have emittances of approximately 1.2–2.3 π mm-rad horizontally and 0.6–1.0 π mm-rad vertically, a horizontal dispersion of 90–190 mm and momentum spreads of about 25 MeV/c. There is reasonable agreement between the measured parameters of the beams and the results of simulations. The beams are found to meet the requirements of MICE

Exuberant fibroblast activity compromises lung function via ADAMTS4

© 2020, The Author(s), under exclusive licence to Springer Nature Limited. Severe respiratory infections can result in acute respiratory distress syndrome (ARDS)1. There are no effective pharmacological therapies that have been shown to improve outcomes for patients with ARDS. Although the host inflammatory response limits spread of and eventually clears the pathogen, immunopathology is a major contributor to tissue damage and ARDS1,2. Here we demonstrate that respiratory viral infection induces distinct fibroblast activation states, which we term extracellular matrix (ECM)-synthesizing, damage-responsive and interferon-responsive states. We provide evidence that excess activity of damage-responsive lung fibroblasts drives lethal immunopathology during severe influenza virus infection. By producing ECM-remodelling enzymes—in particular the ECM protease ADAMTS4—and inflammatory cytokines, damage-responsive fibroblasts modify the lung microenvironment to promote robust immune cell infiltration at the expense of lung function. In three cohorts of human participants, the levels of ADAMTS4 in the lower respiratory tract were associated with the severity of infection with seasonal or avian influenza virus. A therapeutic agent that targets the ECM protease activity of damage-responsive lung fibroblasts could provide a promising approach to preserving lung function and improving clinical outcomes following severe respiratory infections

Publisher Correction: Exuberant fibroblast activity compromises lung function via ADAMTS4 (Nature, (2020), 587, 7834, (466-471), 10.1038/s41586-020-2877-5)

© 2020, The Author(s), under exclusive licence to Springer Nature Limited. An amendment to this paper has been published and can be accessed via a link at the top of the paper

Electron-muon ranger: performance in the MICE muon beam

The Muon Ionization Cooling Experiment (MICE) will perform a detailed study of ionization cooling to evaluate the feasibility of the technique. To carry out this program, MICE requires an efficient particle-identification (PID) system to identify muons. The Electron-Muon Ranger (EMR) is a fully-active tracking-calorimeter that forms part of the PID system and tags muons that traverse the cooling channel without decaying. The detector is capable of identifying electrons with an efficiency of 98.6%, providing a purity for the MICE beam that exceeds 99.8%. The EMR also proved to be a powerful tool for the reconstruction of muon momenta in the range 100–280 MeV/c