Lipopolysaccharide induces recurrence of arthritis in rat joints previously injured by peptidoglycan-polysaccharide

Rat ankle joints injected intraarticularly with 5 micrograms of group A streptococcal peptidoglycan-polysaccharide (PG-APS) developed an acute course of arthritis. Recurrence of arthritis was induced in 100% of these joints by intravenous injection of as little as 10 micrograms of Salmonella typhimurium lipopolysaccharide (LPS) 3 wk after intraarticular injection. This reaction was similar in athymic and euthymic rats. Buffalo rats were less susceptible than Lewis or Sprague- Dawley rats. Neisseria gonorrhoeae, Yersinia enterocolitica, and Escherichia coli LPS, and S. typhimurium Re mutant LPS, were also active. Re mutant LPS activity was greatly reduced by mixing with polymyxin B. E. coli lipid A was weakly active. An acute synovitis of much less incidence, severity, and duration was seen in contralateral joints injected initially with saline, and in ankle joints of naive, previously uninjected rats after intravenous LPS injection. The intravenous injection of the muramidase mutanolysin on day 0 or 7 after intraarticular PG-APS injection prevented LPS-induced recurrence of arthritis. These studies suggest that the phlogistic activities of lipid A and peptidoglycan might interact in an inflammatory disease process, and that LPS may play a role in recurrent episodes of rheumatoid arthritis or reactive arthritis

Multi-Messenger Gravitational Wave Searches with Pulsar Timing Arrays: Application to 3C66B Using the NANOGrav 11-year Data Set

When galaxies merge, the supermassive black holes in their centers may form binaries and, during the process of merger, emit low-frequency gravitational radiation in the process. In this paper we consider the galaxy 3C66B, which was used as the target of the first multi-messenger search for gravitational waves. Due to the observed periodicities present in the photometric and astrometric data of the source of the source, it has been theorized to contain a supermassive black hole binary. Its apparent 1.05-year orbital period would place the gravitational wave emission directly in the pulsar timing band. Since the first pulsar timing array study of 3C66B, revised models of the source have been published, and timing array sensitivities and techniques have improved dramatically. With these advances, we further constrain the chirp mass of the potential supermassive black hole binary in 3C66B to less than $(1.65\pm0.02) \times 10^9~{M_\odot}$ using data from the NANOGrav 11-year data set. This upper limit provides a factor of 1.6 improvement over previous limits, and a factor of 4.3 over the first search done. Nevertheless, the most recent orbital model for the source is still consistent with our limit from pulsar timing array data. In addition, we are able to quantify the improvement made by the inclusion of source properties gleaned from electromagnetic data to `blind' pulsar timing array searches. With these methods, it is apparent that it is not necessary to obtain exact a priori knowledge of the period of a binary to gain meaningful astrophysical inferences.Comment: 14 pages, 6 figures. Accepted by Ap

Discovery, Timing, and Multiwavelength Observations of the Black Widow Millisecond Pulsar PSR J1555-2908

We report the discovery of PSR J1555-2908, a 1.79 ms radio and gamma-ray pulsar in a 5.6 hr binary system with a minimum companion mass of 0.052 $M_\odot$. This fast and energetic ($\dot E = 3 \times 10^{35}$ erg/s) millisecond pulsar was first detected as a gamma-ray point source in Fermi LAT sky survey observations. Guided by a steep spectrum radio point source in the Fermi error region, we performed a search at 820 MHz with the Green Bank Telescope that first discovered the pulsations. The initial radio pulse timing observations provided enough information to seed a search for gamma-ray pulsations in the LAT data, from which we derive a timing solution valid for the full Fermi mission. In addition to the radio and gamma-ray pulsation discovery and timing, we searched for X-ray pulsations using NICER but no significant pulsations were detected. We also obtained time-series r-band photometry that indicates strong heating of the companion star by the pulsar wind. Material blown off the heated companion eclipses the 820 MHz radio pulse during inferior conjunction of the companion for ~10% of the orbit, which is twice the angle subtended by its Roche lobe in an edge-on system

The NANOGrav 11-Year Data Set: Limits on Gravitational Waves from Individual Supermassive Black Hole Binaries

Observations indicate that nearly all galaxies contain supermassive black holes (SMBHs) at their centers. When galaxies merge, their component black holes form SMBH binaries (SMBHBs), which emit low-frequency gravitational waves (GWs) that can be detected by pulsar timing arrays (PTAs). We have searched the recently-released North American Nanohertz Observatory for Gravitational Waves (NANOGrav) 11-year data set for GWs from individual SMBHBs in circular orbits. As we did not find strong evidence for GWs in our data, we placed 95\% upper limits on the strength of GWs from such sources as a function of GW frequency and sky location. We placed a sky-averaged upper limit on the GW strain of $h_0 < 7.3(3) \times 10^{-15}$ at $f_\mathrm{gw}= 8$ nHz. We also developed a technique to determine the significance of a particular signal in each pulsar using ``dropout' parameters as a way of identifying spurious signals in measurements from individual pulsars. We used our upper limits on the GW strain to place lower limits on the distances to individual SMBHBs. At the most-sensitive sky location, we ruled out SMBHBs emitting GWs with $f_\mathrm{gw}= 8$ nHz within 120 Mpc for $\mathcal{M} = 10^9 \, M_\odot$, and within 5.5 Gpc for $\mathcal{M} = 10^{10} \, M_\odot$. We also determined that there are no SMBHBs with $\mathcal{M} > 1.6 \times 10^9 \, M_\odot$ emitting GWs in the Virgo Cluster. Finally, we estimated the number of potentially detectable sources given our current strain upper limits based on galaxies in Two Micron All-Sky Survey (2MASS) and merger rates from the Illustris cosmological simulation project. Only 34 out of 75,000 realizations of the local Universe contained a detectable source, from which we concluded it was unsurprising that we did not detect any individual sources given our current sensitivity to GWs.Comment: 10 pages, 11 figures. Accepted by Astrophysical Journal. Please send any comments/questions to S. J. Vigeland ([email protected]

Neutron star mass estimates from gamma-ray eclipses in spider millisecond pulsar binaries

Reliable neutron star mass measurements are key to determining the equation-of-state of cold nuclear matter, but these are rare. "Black Widows" and "Redbacks" are compact binaries consisting of millisecond pulsars and semi-degenerate companion stars. Spectroscopy of the optically bright companions can determine their radial velocities, providing inclination-dependent pulsar mass estimates. While inclinations can be inferred from subtle features in optical light curves, such estimates may be systematically biased due to incomplete heating models and poorly-understood variability. Using data from the Fermi Large Area Telescope, we have searched for gamma-ray eclipses from 49 spider systems, discovering significant eclipses in 7 systems, including the prototypical black widow PSR B1957$+$20. Gamma-ray eclipses require direct occultation of the pulsar by the companion, and so the detection, or significant exclusion, of a gamma-ray eclipse strictly limits the binary inclination angle, providing new robust, model-independent pulsar mass constraints. For PSR B1957$+$20, the eclipse implies a much lighter pulsar ($M_{\rm psr} = 1.81 \pm 0.07\,M_{\odot}$) than inferred from optical light curve modelling.Comment: 31 pages, 4 figures, includes supplementary tables; published in Nature Astronom

Flavin-Induced Oligomerization in Escherichia coli Adaptive Response Protein AidB

The process known as “adaptive response” allows Escherichia coli to respond to small doses of DNA-methylating agents by upregulating the expression of four proteins. While the role of three of these proteins in mitigating DNA damage is well understood, the function of AidB is less clear. Although AidB is a flavoprotein, no catalytic role has been established for the bound cofactor. Here we investigate the possibility that flavin plays a structural role in the assembly of the AidB tetramer. We report the generation and biophysical characterization of deflavinated AidB and of an AidB mutant that has greatly reduced affinity for flavin adenine dinucleotide (FAD). Using fluorescence quenching and analytical ultracentrifugation, we find that apo AidB has a high affinity for FAD, as indicated by an apparent dissociation constant of 402.1 ± 35.1 nM, and that binding of substoichiometric amounts of FAD triggers a transition in the AidB oligomeric state. In particular, deflavinated AidB is dimeric, whereas the addition of FAD yields a tetramer. We further investigate the dimerization and tetramerization interfaces of AidB by determining a 2.8 Å resolution crystal structure in space group P32 that contains three intact tetramers in the asymmetric unit. Taken together, our findings provide strong evidence that FAD plays a structural role in the formation of tetrameric AidB.National Institutes of Health (U.S.) (grant R01-GM0272663)National Institutes of Health (U.S.) (grant P30-ES002109)National Science Foundation (U.S.) (grant MCB-0543833

The NANOGrav 11-year Data Set: High-precision Timing of 45 Millisecond Pulsars

We present high-precision timing data over time spans of up to 11 years for 45 millisecond pulsars observed as part of the North American Nanohertz Observatory for Gravitational Waves (NANOGrav) project, aimed at detecting and characterizing low-frequency gravitational waves. The pulsars were observed with the Arecibo Observatory and/or the Green Bank Telescope at frequencies ranging from 327 MHz to 2.3 GHz. Most pulsars were observed with approximately monthly cadence, and six high-timing-precision pulsars were observed weekly. All were observed at widely separated frequencies at each observing epoch in order to fit for time-variable dispersion delays. We describe our methods for data processing, time-of-arrival (TOA) calculation, and the implementation of a new, automated method for removing outlier TOAs. We fit a timing model for each pulsar that includes spin, astrometric, and (for binary pulsars) orbital parameters; time-variable dispersion delays; and parameters that quantify pulse-profile evolution with frequency. The timing solutions provide three new parallax measurements, two new Shapiro delay measurements, and two new measurements of significant orbital-period variations. We fit models that characterize sources of noise for each pulsar. We find that 11 pulsars show significant red noise, with generally smaller spectral indices than typically measured for non-recycled pulsars, possibly suggesting a different origin. A companion paper uses these data to constrain the strength of the gravitational-wave background

The NANOGrav 12.5-Year Data Set: Dispersion Measure Mis-Estimation with Varying Bandwidths

Noise characterization for pulsar-timing applications accounts for interstellar dispersion by assuming a known frequency-dependence of the delay it introduces in the times of arrival (TOAs). However, calculations of this delay suffer from mis-estimations due to other chromatic effects in the observations. The precision in modeling dispersion is dependent on the observed bandwidth. In this work, we calculate the offsets in infinite-frequency TOAs due to mis-estimations in the modeling of dispersion when using varying bandwidths at the Green Bank Telescope. We use a set of broadband observations of PSR J1643-1224, a pulsar with an excess of chromatic noise in its timing residuals. We artificially restricted these observations to a narrowband frequency range, then used both data sets to calculate residuals with a timing model that does not include short-scale dispersion variations. By fitting the resulting residuals to a dispersion model, and comparing the ensuing fitted parameters, we quantify the dispersion mis-estimations. Moreover, by calculating the autocovariance function of the parameters we obtained a characteristic timescale over which the dispersion mis-estimations are correlated. For PSR J1643-1224, which has one of the highest dispersion measures (DM) in the NANOGrav pulsar timing array, we find that the infinite-frequency TOAs suffer from a systematic offset of ~22 microseconds due to DM mis-estimations, with correlations over ~1 month. For lower-DM pulsars, the offset is ~7 microseconds. This error quantification can be used to provide more robust noise modeling in NANOGrav's data, thereby increasing sensitivity and improving parameter estimation in gravitational wave searches.Comment: 15 pages, 7 figure

The NANOGrav 12.5-Year Data Set:Dispersion Measure Misestimations with Varying Bandwidths

Noise characterization for pulsar-timing applications accounts for interstellar dispersion by assuming a known frequency dependence of the delay it introduces in the times of arrival (TOAs). However, calculations of this delay suffer from misestimations due to other chromatic effects in the observations. The precision in modeling dispersion is dependent on the observed bandwidth. In this work, we calculate the offsets in infinite-frequency TOAs due to misestimations in the modeling of dispersion when using varying bandwidths at the Green Bank Telescope. We use a set of broadband observations of PSR J1643−1224, a pulsar with unusual chromatic timing behavior. We artificially restricted these observations to a narrowband frequency range, then used both the broad- and narrowband data sets to calculate residuals with a timing model that does not account for time variations in the dispersion. By fitting the resulting residuals to a dispersion model and comparing the fits, we quantify the error introduced in the timing parameters due to using a reduced frequency range. Moreover, by calculating the autocovariance function of the parameters, we obtained a characteristic timescale over which the dispersion misestimates are correlated. For PSR J1643−1224, which has one of the highest dispersion measures (DM) in the NANOGrav pulsar timing array, we find that the infinite-frequency TOAs suffer from a systematic offset of ∼22 μs due to incomplete frequency sampling, with correlations over about one month. For lower-DM pulsars, the offset is ∼7 μs. This error quantification can be used to provide more robust noise modeling in the NANOGrav data, thereby increasing the sensitivity and improving the parameter estimation in gravitational wave searches

An Unusual Pulse Shape Change Event in PSR J1713+0747 Observed with the Green Bank Telescope and CHIME

The millisecond pulsar J1713+0747 underwent a sudden and significant pulse shape change between 2021 April 16 and 17 (MJDs 59320 and 59321). Subsequently, the pulse shape gradually recovered over the course of several months. We report the results of continued multifrequency radio observations of the pulsar made using the Canadian Hydrogen Intensity Mapping Experiment and the 100 m Green Bank Telescope in a 3 yr period encompassing the shape change event, between 2020 February and 2023 February. As of 2023 February, the pulse shape had returned to a state similar to that seen before the event, but with measurable changes remaining. The amplitude of the shape change and the accompanying time-of-arrival residuals display a strong nonmonotonic dependence on radio frequency, demonstrating that the event is neither a glitch (the effects of which should be independent of radio frequency, ν) nor a change in dispersion measure alone (which would produce a delay proportional to ν−2). However, it does bear some resemblance to the two previous "chromatic timing events" observed in J1713+0747, as well as to a similar event observed in PSR J1643−1224 in 2015