Sialylation of MUC4β N-glycans by ST6GAL1 orchestrates human airway epithelial cell differentiation associated with type-2 inflammation

Although type-2-induced (T2-induced) epithelial dysfunction is likely to profoundly alter epithelial differentiation and repair in asthma, the mechanisms for these effects are poorly understood. A role for specific mucins, heavily N-glycosylated epithelial glycoproteins, in orchestrating epithelial cell fate in response to T2 stimuli has not previously been investigated. Levels of a sialylated MUC4 beta isoform were found to be increased in airway specimens from asthmatic patients in association with T2 inflammation. We hypothesized that IL-13 would increase sialylation of MUC4 beta, thereby altering its function and that the beta-galactoside alpha-2,6-sialyltransferase 1 (ST6GAL1) would regulate the sialylation. Using human biologic specimens and cultured primary human airway epithelial cells (HAECs), we demonstrated that IL-13 increases ST6GAL1-mediated sialylation of MUC4 beta and that both were increased in asthma, particularly in sputum supernatant and/or fresh isolated HAECs with elevated T2 biomarkers. ST6GAL1-induced sialylation of MUC4 beta altered its lectin binding and secretion. Both ST6GAL1 and MUC4 beta inhibited epithelial cell proliferation while promoting goblet cell differentiation. These in vivo and in vitro data provide strong evidence for a critical role for ST6GAL1-induced sialylation of MUC4 beta in epithelial dysfunction associated with T2-high asthma, thereby identifying specific sialylation pathways as potential targets in asthma.NIH [R01 HL069174]; National Heart, Lung, and Blood Institute [R01 HL064937, R01 HL069116, P01 HL103453, R01 HL69167, U01 HL109086, U10 HL109152, R21 AI122071]; National Institute of Allergy and Infectious Diseases [P01 AI106684]; Nikon A1 [NIH 1S10OD019973-01]This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Gravitational Waves From Known Pulsars: Results From The Initial Detector Era

We present the results of searches for gravitational waves from a large selection of pulsars using data from the most recent science runs (S6, VSR2 and VSR4) of the initial generation of interferometric gravitational wave detectors LIGO (Laser Interferometric Gravitational-wave Observatory) and Virgo. We do not see evidence for gravitational wave emission from any of the targeted sources but produce upper limits on the emission amplitude. We highlight the results from seven young pulsars with large spin-down luminosities. We reach within a factor of five of the canonical spin-down limit for all seven of these, whilst for the Crab and Vela pulsars we further surpass their spin-down limits. We present new or updated limits for 172 other pulsars (including both young and millisecond pulsars). Now that the detectors are undergoing major upgrades, and, for completeness, we bring together all of the most up-to-date results from all pulsars searched for during the operations of the first-generation LIGO, Virgo and GEO600 detectors. This gives a total of 195 pulsars including the most recent results described in this paper.United States National Science FoundationScience and Technology Facilities Council of the United KingdomMax-Planck-SocietyState of Niedersachsen/GermanyAustralian Research CouncilInternational Science Linkages program of the Commonwealth of AustraliaCouncil of Scientific and Industrial Research of IndiaIstituto Nazionale di Fisica Nucleare of ItalySpanish Ministerio de Economia y CompetitividadConselleria d'Economia Hisenda i Innovacio of the Govern de les Illes BalearsNetherlands Organisation for Scientific ResearchPolish Ministry of Science and Higher EducationFOCUS Programme of Foundation for Polish ScienceRoyal SocietyScottish Funding CouncilScottish Universities Physics AllianceNational Aeronautics and Space AdministrationOTKA of HungaryLyon Institute of Origins (LIO)National Research Foundation of KoreaIndustry CanadaProvince of Ontario through the Ministry of Economic Development and InnovationNational Science and Engineering Research Council CanadaCarnegie TrustLeverhulme TrustDavid and Lucile Packard FoundationResearch CorporationAlfred P. Sloan FoundationAstronom

Search of the Orion spur for continuous gravitational waves using a loosely coherent algorithm on data from LIGO interferometers

We report results of a wideband search for periodic gravitational waves from isolated neutron stars within the Orion spur towards both the inner and outer regions of our Galaxy. As gravitational waves interact very weakly with matter, the search is unimpeded by dust and concentrations of stars. One search disk (A) is 6.87° in diameter and centered on 20h10m54.71s+33°33′25.29′′, and the other (B) is 7.45° in diameter and centered on 8h35m20.61s-46°49′25.151′′. We explored the frequency range of 50-1500 Hz and frequency derivative from 0 to -5×10-9 Hz/s. A multistage, loosely coherent search program allowed probing more deeply than before in these two regions, while increasing coherence length with every stage. Rigorous follow-up parameters have winnowed the initial coincidence set to only 70 candidates, to be examined manually. None of those 70 candidates proved to be consistent with an isolated gravitational-wave emitter, and 95% confidence level upper limits were placed on continuous-wave strain amplitudes. Near 169 Hz we achieve our lowest 95% C.L. upper limit on the worst-case linearly polarized strain amplitude h0 of 6.3×10-25, while at the high end of our frequency range we achieve a worst-case upper limit of 3.4×10-24 for all polarizations and sky locations. © 2016 American Physical Society

Constraints on the cosmic expansion history from GWTC-3

We use 47 gravitational-wave sources from the Third LIGO-Virgo-KAGRA Gravitational-Wave Transient Catalog (GWTC-3) to estimate the Hubble parameter $H(z)$, including its current value, the Hubble constant $H_0$. Each gravitational-wave (GW) signal provides the luminosity distance to the source and we estimate the corresponding redshift using two methods: the redshifted masses and a galaxy catalog. Using the binary black hole (BBH) redshifted masses, we simultaneously infer the source mass distribution and $H(z)$. The source mass distribution displays a peak around $34\, {\rm M_\odot}$, followed by a drop-off. Assuming this mass scale does not evolve with redshift results in a $H(z)$ measurement, yielding $H_0=68^{+12}_{-7} {\rm km\,s^{-1}\,Mpc^{-1}}$ ($68\%$ credible interval) when combined with the $H_0$ measurement from GW170817 and its electromagnetic counterpart. This represents an improvement of 17% with respect to the $H_0$ estimate from GWTC-1. The second method associates each GW event with its probable host galaxy in the catalog GLADE+, statistically marginalizing over the redshifts of each event's potential hosts. Assuming a fixed BBH population, we estimate a value of $H_0=68^{+8}_{-6} {\rm km\,s^{-1}\,Mpc^{-1}}$ with the galaxy catalog method, an improvement of 42% with respect to our GWTC-1 result and 20% with respect to recent $H_0$ studies using GWTC-2 events. However, we show that this result is strongly impacted by assumptions about the BBH source mass distribution; the only event which is not strongly impacted by such assumptions (and is thus informative about $H_0$) is the well-localized event GW190814

The population of merging compact binaries inferred using gravitational waves through GWTC-3

We report on the population properties of 76 compact binary mergers detected with gravitational waves below a false alarm rate of 1 per year through GWTC-3. The catalog contains three classes of binary mergers: BBH, BNS, and NSBH mergers. We infer the BNS merger rate to be between 10 $\rm{Gpc^{-3} yr^{-1}}$ and 1700 $\rm{Gpc^{-3} yr^{-1}}$ and the NSBH merger rate to be between 7.8 $\rm{Gpc^{-3}\, yr^{-1}}$ and 140 $\rm{Gpc^{-3} yr^{-1}}$ , assuming a constant rate density versus comoving volume and taking the union of 90% credible intervals for methods used in this work. Accounting for the BBH merger rate to evolve with redshift, we find the BBH merger rate to be between 17.9 $\rm{Gpc^{-3}\, yr^{-1}}$ and 44 $\rm{Gpc^{-3}\, yr^{-1}}$ at a fiducial redshift (z=0.2). We obtain a broad neutron star mass distribution extending from $1.2^{+0.1}_{-0.2} M_\odot$ to $2.0^{+0.3}_{-0.3} M_\odot$. We can confidently identify a rapid decrease in merger rate versus component mass between neutron star-like masses and black-hole-like masses, but there is no evidence that the merger rate increases again before 10 $M_\odot$. We also find the BBH mass distribution has localized over- and under-densities relative to a power law distribution. While we continue to find the mass distribution of a binary's more massive component strongly decreases as a function of primary mass, we observe no evidence of a strongly suppressed merger rate above $\sim 60 M_\odot$. The rate of BBH mergers is observed to increase with redshift at a rate proportional to $(1+z)^{\kappa}$ with $\kappa = 2.9^{+1.7}_{-1.8}$ for $z\lesssim 1$. Observed black hole spins are small, with half of spin magnitudes below $\chi_i \simeq 0.25$. We observe evidence of negative aligned spins in the population, and an increase in spin magnitude for systems with more unequal mass ratio

Search for continuous gravitational wave emission from the Milky Way center in O3 LIGO--Virgo data

We present a directed search for continuous gravitational wave (CW) signals emitted by spinning neutron stars located in the inner parsecs of the Galactic Center (GC). Compelling evidence for the presence of a numerous population of neutron stars has been reported in the literature, turning this region into a very interesting place to look for CWs. In this search, data from the full O3 LIGO--Virgo run in the detector frequency band $[10,2000]\rm~Hz$ have been used. No significant detection was found and 95$\%$ confidence level upper limits on the signal strain amplitude were computed, over the full search band, with the deepest limit of about $7.6\times 10^{-26}$ at $\simeq 142\rm~Hz$. These results are significantly more constraining than those reported in previous searches. We use these limits to put constraints on the fiducial neutron star ellipticity and r-mode amplitude. These limits can be also translated into constraints in the black hole mass -- boson mass plane for a hypothetical population of boson clouds around spinning black holes located in the GC.Comment: 25 pages, 5 figure

Search for Gravitational Waves Associated with Gamma-Ray Bursts Detected by Fermi and Swift during the LIGO-Virgo Run O3b

We search for gravitational-wave signals associated with gamma-ray bursts (GRBs) detected by the Fermi and Swift satellites during the second half of the third observing run of Advanced LIGO and Advanced Virgo (2019 November 1 15:00 UTC-2020 March 27 17:00 UTC). We conduct two independent searches: A generic gravitational-wave transients search to analyze 86 GRBs and an analysis to target binary mergers with at least one neutron star as short GRB progenitors for 17 events. We find no significant evidence for gravitational-wave signals associated with any of these GRBs. A weighted binomial test of the combined results finds no evidence for subthreshold gravitational-wave signals associated with this GRB ensemble either. We use several source types and signal morphologies during the searches, resulting in lower bounds on the estimated distance to each GRB. Finally, we constrain the population of low-luminosity short GRBs using results from the first to the third observing runs of Advanced LIGO and Advanced Virgo. The resulting population is in accordance with the local binary neutron star merger rate. © 2022. The Author(s). Published by the American Astronomical Society