A fast radio burst localized at detection to a galactic disk using very long baseline interferometry

Fast radio bursts (FRBs) are millisecond-duration, luminous radio transients of extragalactic origin. These events have been used to trace the baryonic structure of the Universe using their dispersion measure (DM) assuming that the contribution from host galaxies can be reliably estimated. However, contributions from the immediate environment of an FRB may dominate the observed DM, thus making redshift estimates challenging without a robust host galaxy association. Furthermore, while at least one Galactic burst has been associated with a magnetar, other localized FRBs argue against magnetars as the sole progenitor model. Precise localization within the host galaxy can discriminate between progenitor models, a major goal of the field. Until now, localizations on this spatial scale have only been carried out in follow-up observations of repeating sources. Here we demonstrate the localization of FRB 20210603A with very long baseline interferometry (VLBI) on two baselines, using data collected only at the time of detection. We localize the burst to SDSS J004105.82+211331.9, an edge-on galaxy at $z\approx 0.177$, and detect recent star formation in the kiloparsec-scale vicinity of the burst. The edge-on inclination of the host galaxy allows for a unique comparison between the line of sight towards the FRB and lines of sight towards known Galactic pulsars. The DM, Faraday rotation measure (RM), and scattering suggest a progenitor coincident with the host galactic plane, strengthening the link between the environment of FRB 20210603A and the disk of its host galaxy. Single-pulse VLBI localizations of FRBs to within their host galaxies, following the one presented here, will further constrain the origins and host environments of one-off FRBs.Comment: 40 pages, 13 figures, submitted. Fixed typo in abstrac

Sub-second periodicity in a fast radio burst

Fast radio bursts (FRBs) are millisecond-duration flashes of radio waves that are visible at distances of billions of light-years. The nature of their progenitors and their emission mechanism remain open astrophysical questions. Here we report the detection of the multi-component FRB 20191221A and the identification of a periodic separation of 216.8(1) ms between its components with a significance of 6.5 sigmas. The long (~3 s) duration and nine or more components forming the pulse profile make this source an outlier in the FRB population. Such short periodicity provides strong evidence for a neutron-star origin of the event. Moreover, our detection favours emission arising from the neutron-star magnetosphere, as opposed to emission regions located further away from the star, as predicted by some models.Comment: Updated to conform to the accepted versio

Improved Constraints on the 21 cm EoR Power Spectrum and the X-Ray Heating of the IGM with HERA Phase I Observations

We report the most sensitive upper limits to date on the 21 cm epoch of reionization power spectrum using 94 nights of observing with Phase I of the Hydrogen Epoch of Reionization Array (HERA). Using similar analysis techniques as in previously reported limits (HERA Collaboration 2022a), we find at 95% confidence that $\Delta^2(k = 0.34$ $h$ Mpc$^{-1}$) $\leq 457$ mK$^2$ at $z = 7.9$ and that $\Delta^2 (k = 0.36$ $h$ Mpc$^{-1}) \leq 3,496$ mK$^2$ at $z = 10.4$, an improvement by a factor of 2.1 and 2.6 respectively. These limits are mostly consistent with thermal noise over a wide range of $k$ after our data quality cuts, despite performing a relatively conservative analysis designed to minimize signal loss. Our results are validated with both statistical tests on the data and end-to-end pipeline simulations. We also report updated constraints on the astrophysics of reionization and the cosmic dawn. Using multiple independent modeling and inference techniques previously employed by HERA Collaboration (2022b), we find that the intergalactic medium must have been heated above the adiabatic cooling limit at least as early as $z = 10.4$, ruling out a broad set of so-called "cold reionization" scenarios. If this heating is due to high-mass X-ray binaries during the cosmic dawn, as is generally believed, our result's 99% credible interval excludes the local relationship between soft X-ray luminosity and star formation and thus requires heating driven by evolved low-metallicity stars.Comment: 57 pages, 37 figures. Updated to match the accepted ApJ version. Corresponding author: Joshua S. Dillo

The MDM-2 Antagonist Nutlin-3 Promotes the Maturation of Acute Myeloid Leukemic Blasts1

The small-molecule inhibitor of murine double minute (MDM-2), Nutlin-3, induced variable apoptosis in primary acute myeloid leukemia (AML) blasts and promoted myeloid maturation of surviving cells, as demonstrated by analysis of CD11b and CD14 surface antigens and by morphologic examination. Although the best-characterized activity of Nutlin-3 is activation of the p53 pathway, Nutlin-3 induced maturation also in one AML sample characterized by p53 deletion, as well as in the p53-/- human myeloblastic HL-60 cell line. At the molecular level, the maturational activity of Nutlin-3 in HL-60 cells was accompanied by the induction of E2F1 transcription factor, and it was significantly counteracted by specific gene knockdown with small interfering RNA for E2F1. Moreover, Nutlin-3, as well as tumor necrosis factor (TNF) α, potentiated the maturational activity of recombinant TNF-related apoptosis-inducing ligand (TRAIL) in HL-60 cells. However, although TNF-α significantly counteracted the proapoptotic activity of TRAIL, Nutlin-3 did not interfere with the proapoptotic activity of TRAIL. Taken together, these data disclose a novel, potentially relevant therapeutic role for Nutlin-3 in the treatment of both p53 wild-type and p53-/- AML, possibly in association with recombinant TRAIL

Rab27a is a key component of the secretory machinery of azurophilic granules in granulocytes

Neutrophils kill micro-organisms using microbicidal products that they release into the phagosome or into the extracellular space. The secretory machinery utilized by neutrophils is poorly characterized. We show that the small GTPase Rab27a is an essential component of the secretory machinery of azurophilic granules in granulocytes. Rab27a-deficient mice have impaired secretion of MPO (myeloperoxidase) into the plasma in response to lipopolysaccharide. Cell fractionation analysis revealed that Rab27a and the Rab27a effector protein JFC1/Slp1 (synaptotagmin-like protein 1) are distributed principally in the low-density fraction containing a minor population of MPO-containing granules. By immunofluorescence microscopy, we detected Rab27a and JFC1/Slp1 in a minor subpopulation of MPO-containing granules. Interference with the JFC1/Slp1–Rab27a secretory machinery impaired secretion of MPO in permeabilized neutrophils. The expression of Rab27a was dramatically increased when promyelocytic HL-60 cells were differentiated into granulocytes but not when they were differentiated into monocytes. Down-regulation of Rab27a in HL-60 cells by RNA interference did not affect JFC1/Slp1 expression but significantly decreased the secretion of MPO. Neither Rab27a nor JFC1/Slp1 was integrated into the phagolysosome membrane during phagocytosis. Neutrophils from Rab27a-deficient mice efficiently phagocytose zymosan opsonized particles and deliver MPO to the phagosome. We conclude that Rab27a and JFC1/Slp1 permit MPO release into the surrounding milieu and constitute key components of the secretory machinery of azurophilic granules in granulocytes. Our results suggest that the granules implicated in cargo release towards the surrounding milieu are molecularly and mechanistically different from those involved in their release towards the phagolysosome

CHIME/FRB Catalog 1 results: statistical cross-correlations with large-scale structure

The CHIME/FRB Project has recently released its first catalog of fast radio bursts (FRBs), containing 492 unique sources. We present results from angular cross-correlations of CHIME/FRB sources with galaxy catalogs. We find a statistically significant ($p$-value $\sim 10^{-4}$, accounting for look-elsewhere factors) cross-correlation between CHIME FRBs and galaxies in the redshift range $0.3 \lesssim z \lesssim 0.5$, in three photometric galaxy surveys: WISE$\times$SCOS, DESI-BGS, and DESI-LRG. The level of cross-correlation is consistent with an order-one fraction of the CHIME FRBs being in the same dark matter halos as survey galaxies in this redshift range. We find statistical evidence for a population of FRBs with large host dispersion measure ($\sim 400$ pc cm$^{-3}$), and show that this can plausibly arise from gas in large halos ($M \sim 10^{14} M_\odot$), for FRBs near the halo center ($r \lesssim 100$ kpc). These results will improve in future CHIME/FRB catalogs, with more FRBs and better angular resolution.Comment: 26 pages, 16 figures, published in Ap