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

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]

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

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

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

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

Searching for continuous Gravitational Waves in the second data release of the International Pulsar Timing Array

The International Pulsar Timing Array 2nd data release is the combination of datasets from worldwide collaborations. In this study, we search for continuous waves: gravitational wave signals produced by individual supermassive black hole binaries in the local universe. We consider binaries on circular orbits and neglect the evolution of orbital frequency over the observational span. We find no evidence for such signals and set sky averaged 95% upper limits on their amplitude h 95 . The most sensitive frequency is 10nHz with h 95 = 9.1 10-15 . We achieved the best upper limit to date at low and high frequencies of the PTA band thanks to improved effective cadence of observations. In our analysis, we have taken into account the recently discovered common red noise process, which has an impact at low frequencies. We also find that the peculiar noise features present in some pulsars data must be taken into account to reduce the false alarm. We show that using custom noise models is essential in searching for continuous gravitational wave signals and setting the upper limit

A Second Chromatic Timing Event of Interstellar Origin toward PSR J1713+0747

The frequency dependence of radio pulse arrival times provides a probe of structures in the intervening media. Demorest et al. was the first to show a short-term (~100–200 days) reduction in the electron content along the line of sight to PSR J1713+0747 in data from 2008 (approximately MJD 54750) based on an apparent dip in the dispersion measure of the pulsar. We report on a similar event in 2016 (approximately MJD 57510), with average residual pulse-arrival times ≈−3.0, −1.3, and −0.7 μs at 820, 1400, and 2300 MHz, respectively. Timing analyses indicate possible departures from the standard ν −2 dispersive-delay dependence. We discuss and rule out a wide variety of potential interpretations. We find the likeliest scenario to be lensing of the radio emission by some structure in the interstellar medium, which causes multiple frequency-dependent pulse arrival-time delays

The NANOGrav 11 Year Data Set: Pulsar-timing Constraints on the Stochastic Gravitational-wave Background

We search for an isotropic stochastic gravitational-wave background (GWB) in the newly released 11 year data set from the North American Nanohertz Observatory for Gravitational Waves (NANOGrav). While we find no evidence for a GWB, we place constraints on a population of inspiraling supermassive black hole (SMBH) binaries, a network of decaying cosmic strings, and a primordial GWB. For the first time, we find that the GWB constraints are sensitive to the solar system ephemeris (SSE) model used and that SSE errors can mimic a GWB signal. We developed an approach that bridges systematic SSE differences, producing the first pulsar-timing array (PTA) constraints that are robust against SSE errors. We thus place a 95% upper limit on the GW-strain amplitude of A GWB < 1.45 × 10−15 at a frequency of f = 1 yr−1 for a fiducial f −2/3 power-law spectrum and with interpulsar correlations modeled. This is a factor of ~2 improvement over the NANOGrav nine-year limit calculated using the same procedure. Previous PTA upper limits on the GWB (as well as their astrophysical and cosmological interpretations) will need revision in light of SSE systematic errors. We use our constraints to characterize the combined influence on the GWB of the stellar mass density in galactic cores, the eccentricity of SMBH binaries, and SMBH–galactic-bulge scaling relationships. We constrain the cosmic-string tension using recent simulations, yielding an SSE-marginalized 95% upper limit of Gμ < 5.3 × 10−11—a factor of ~2 better than the published NANOGrav nine-year constraints. Our SSE-marginalized 95% upper limit on the energy density of a primordial GWB (for a radiation-dominated post-inflation universe) is ΩGWB(f) h 2 < 3.4 × 10−10

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