Timing of the accreting millisecond pulsar IGR~J17511--3057

{Timing analysis of Accretion-powered Millisecond Pulsars (AMPs) is a powerful tool to probe the physics of compact objects. The recently discovered \newigrj is the 12 discovered out of the 13 AMPs known. The Rossi XTE satellite provided an extensive coverage of the 25 days-long observation of the source outburst.} {Our goal is to investigate the complex interaction between the neutron star magnetic field and the accretion disk, determining the angular momentum exchange between them. The presence of a millisecond coherent flux modulation allows us to investigate such interaction from the study of pulse arrival times. In order to separate the neutron star proper spin frequency variations from other effects, a precise set of orbital ephemeris is mandatory.} {Using timing techniques, we analysed the pulse phase delays fitting differential corrections to the orbital parameters. To remove the effects of pulse phase fluctuations we applied the timing technique already successfully applied to the case of an another AMP, XTE J1807-294.} {We report a precise set of orbital ephemeris. We demonstrate that the companion star is a main sequence star. We find pulse phase delays fluctuations on the first harmonic with a characteristic amplitude of about 0.05, similar to what also observed in the case of the AMP XTE J1814-338. For the second time an AMP shows a third harmonic detected during the entire outburst. The first harmonic phase delays show a puzzling behaviour, while the second harmonic phase delays show a clear spin-up. Also the third harmonic shows a spin-up, although not highly significant (3$\sigma$ c.l.). The presence of a fourth harmonic is also reported. In the hypothesis that the second harmonic is a good tracer of the spin frequency of the neutron star, we find a mean spin frequency derivative for this source of \np{1.65(18)}{-13} Hz s$^{-1}$.} (continue ...)Comment: 9 pages, 12 figures, A&A accepted on 23/10/201

The ADMA/DDAH Pathway Regulates VEGF-Mediated Angiogenesis

Objectives— Asymmetrical dimethylarginine (ADMA) is a nitric oxide synthase (NOS) inhibitor and cardiovascular risk factor associated with angiogenic disorders. Enzymes metabolising ADMA, dimethylarginine dimethylaminohydrolases (DDAH) promote angiogenesis, but the mechanisms are not clear. We hypothesized that ADMA/DDAH modifies endothelial responses to vascular endothelial growth factor (VEGF) by affecting activity of Rho GTPases, regulators of actin polymerization, and focal adhesion dynamics. Methods and Results— The effects of ADMA on VEGF-induced endothelial cell motility, focal adhesion turnover, and angiogenesis were studied in human umbilical vein endothelial cells (HUVECs) and DDAH I heterozygous knockout mice. ADMA inhibited VEGF-induced chemotaxis in vitro and angiogenesis in vitro and in vivo in an NO-dependent way. ADMA effects were prevented by overexpression of DDAH but were not associated with decreased proliferation, increased apoptosis, or changes in VEGFR-2 activity or expression. ADMA inhibited endothelial cell polarization, protrusion formation, and decreased focal adhesion dynamics, resulting from Rac1 inhibition after decrease in phosphorylation of vasodilator stimulated phosphoprotein (VASP). Constitutively active Rac1, and to a lesser extent dominant negative RhoA, abrogated ADMA effects in vitro and in vivo. Conclusion— The ADMA/DDAH pathway regulates VEGF-induced angiogenesis in an NO- and Rac1-dependent manner

Structural and functional differences in PHOX2B frameshift mutations underlie isolated or syndromic congenital central hypoventilation syndrome

Heterozygous mutations in the PHOX2B gene are causative of congenital central hypoventilation syndrome (CCHS), a neurocristopathy characterized by defective autonomic control of breathing due to the impaired differentiation of neural crest cells. Among PHOX2B mutations, polyalanine (polyAla) expansions are almost exclusively associated with isolated CCHS, whereas frameshift variants, although less frequent, are often more severe than polyAla expansions and identified in syndromic CCHS. This article provides a complete review of all the frameshift mutations identified in cases of isolated and syndromic CCHS reported in the literature as well as those identified by us and not yet published. These were considered in terms of both their structure, whether the underlying indels induced frameshifts of either 1 or 2 steps (\u201cframe 2\u201d and \u201cframe 3\u201d mutations respectively), and clinical associations. Furthermore, we evaluated the structural and functional effects of one \u201cframe 3\u201d mutation identified in a patient with isolated CCHS, and one \u201cframe 2\u201d mutation identified in a patient with syndromic CCHS, also affected with Hirschsprung's disease and neuroblastoma. The data thus obtained confirm that the type of translational frame affects the severity of the transcriptional dysfunction and the predisposition to isolated or syndromic CCH

Sardinia Radio Telescope wide-band spectral-polarimetric observations of the galaxy cluster 3C 129

We present new observations of the galaxy cluster 3C 129 obtained with the Sardinia Radio Telescope in the frequency range 6000-7200 MHz, with the aim to image the large-angular-scale emission at high-frequency of the radio sources located in this cluster of galaxies. The data were acquired using the recently-commissioned ROACH2-based backend to produce full-Stokes image cubes of an area of 1 deg x 1 deg centered on the radio source 3C 129. We modeled and deconvolved the telescope beam pattern from the data. We also measured the instrumental polarization beam patterns to correct the polarization images for off-axis instrumental polarization. Total intensity images at an angular resolution of 2.9 arcmin were obtained for the tailed radio galaxy 3C 129 and for 13 more sources in the field, including 3C 129.1 at the galaxy cluster center. These data were used, in combination with literature data at lower frequencies, to derive the variation of the synchrotron spectrum of 3C 129 along the tail of the radio source. If the magnetic field is at the equipartition value, we showed that the lifetimes of radiating electrons result in a radiative age for 3C 129 of t_syn = 267 +/- 26 Myrs. Assuming a linear projected length of 488 kpc for the tail, we deduced that 3C 129 is moving supersonically with a Mach number of M=v_gal/c_s=1.47. Linearly polarized emission was clearly detected for both 3C 129 and 3C 129.1. The linear polarization measured for 3C 129 reaches levels as high as 70% in the faintest region of the source where the magnetic field is aligned with the direction of the tail.Comment: 19 pages, 17 figures, accepted for publication in MNRA

NuSTAR reveals the hidden nature of SS433

SS433 is the only Galactic binary system known to accrete at highly super-critical rates, analogous to tidal disruption events, and needed to explain the mass of some high redshift quasars. Probing the inner regions of SS433 in the X-rays is crucial to understanding this system, and super-critical accretion in general, but has not yet been possible due to obscuration. NuSTAR observed SS433 in the hard X-ray band across multiple phases of its super-orbital precession period. Spectral-timing tools have allowed us to confirm that the hard X-ray emission from the inner regions is scattered towards us by the walls of the wind-cone. By comparing to numerical models, we determine an intrinsic X-ray luminosity of >= 3x10^37 erg/s and that, if viewed face on, the apparent luminosity would be > 1x10^39 erg/s, confirming its long-suspected nature as an ultraluminous X-ray source (ULX). A lag due to absorption by Fe XXV/XXVI in outflowing material travelling at least 0.14-0.29c matches absorption lines seen in ULXs and - in future - will allow us to map a super-critical outflow for the first time.Comment: 24 pages, 8 figures, submitted for publicatio

Renin Angiotensin System Blockers and Risk of Mortality in Hypertensive Patients Hospitalized for COVID-19: An Italian Registry

Background: It is uncertain whether exposure to renin\u2013angiotensin system (RAS) modifiers affects the severity of the new coronavirus disease 2019 (COVID-19) because most of the available studies are retrospective. Methods: We tested the prognostic value of exposure to RAS modifiers (either angiotensin-converting enzyme inhibitors [ACE-Is] or angiotensin receptor blockers [ARBs]) in a prospective study of hypertensive patients with COVID-19. We analyzed data from 566 patients (mean age 75 years, 54% males, 162 ACE-Is users, and 147 ARBs users) hospitalized in five Italian hospitals. The study used systematic prospective data collection according to a pre-specified protocol. All-cause mortality during hospitalization was the primary outcome. Results: Sixty-six patients died during hospitalization. Exposure to RAS modifiers was associated with a significant reduction in the risk of in-hospital mortality when compared to other BP-lowering strategies (odds ratio [OR]: 0.54, 95% confidence interval [CI]: 0.32 to 0.90, p = 0.019). Exposure to ACE-Is was not significantly associated with a reduced risk of in-hospital mortality when compared with patients not treated with RAS modifiers (OR: 0.66, 95% CI: 0.36 to 1.20, p = 0.172). Conversely, ARBs users showed a 59% lower risk of death (OR: 0.41, 95% CI: 0.20 to 0.84, p = 0.016) even after allowance for several prognostic markers, including age, oxygen saturation, occurrence of severe hypotension during hospitalization, and lymphocyte count (adjusted OR: 0.37, 95% CI: 0.17 to 0.80, p = 0.012). The discontinuation of RAS modifiers during hospitalization did not exert a significant effect (p = 0.515). Conclusions: This prospective study indicates that exposure to ARBs reduces mortality in hospitalized patients with COVID-19

Imaging of SNR IC443 and W44 with the Sardinia Radio Telescope at 1.5 GHz and 7 GHz

Observations of supernova remnants (SNRs) are a powerful tool for investigating the later stages of stellar evolution, the properties of the ambient interstellar medium, and the physics of particle acceleration and shocks. For a fraction of SNRs, multi-wavelength coverage from radio to ultra high-energies has been provided, constraining their contributions to the production of Galactic cosmic rays. Although radio emission is the most common identifier of SNRs and a prime probe for refining models, high-resolution images at frequencies above 5 GHz are surprisingly lacking, even for bright and well-known SNRs such as IC443 and W44. In the frameworks of the Astronomical Validation and Early Science Program with the 64-m single-dish Sardinia Radio Telescope, we provided, for the first time, single-dish deep imaging at 7 GHz of the IC443 and W44 complexes coupled with spatially-resolved spectra in the 1.5-7 GHz frequency range. Our images were obtained through on-the-fly mapping techniques, providing antenna beam oversampling and resulting in accurate continuum flux density measurements. The integrated flux densities associated with IC443 are S_1.5GHz = 134 +/- 4 Jy and S_7GHz = 67 +/- 3 Jy. For W44, we measured total flux densities of S_1.5GHz = 214 +/- 6 Jy and S_7GHz = 94 +/- 4 Jy. Spectral index maps provide evidence of a wide physical parameter scatter among different SNR regions: a flat spectrum is observed from the brightest SNR regions at the shock, while steeper spectral indices (up to 0.7) are observed in fainter cooling regions, disentangling in this way different populations and spectra of radio/gamma-ray-emitting electrons in these SNRs.Comment: 13 pages, 9 figures, accepted for publication to MNRAS on 18 May 201

MAXI and NuSTAR observations of the faint X-ray transient MAXI J1848-015 in the GLIMPSE-C01 Cluster

We present the results of MAXI monitoring and two NuSTAR observations of the recently discovered faint X-ray transient MAXI J1848-015. Analysis of the MAXI light-curve shows that the source underwent a rapid flux increase beginning on 2020 December 20, followed by a rapid decrease in flux after only $\sim5$ days. NuSTAR observations reveal that the source transitioned from a bright soft state with unabsorbed, bolometric ($0.1$-$100$ keV) flux $F=6.9 \pm 0.1 \times 10^{-10}\,\mathrm{erg\,cm^{-2}\,s^{-1}}$, to a low hard state with flux $F=2.85 \pm 0.04 \times 10^{-10}\,\mathrm{erg\,cm^{-2}\,s^{-1}}$. Given a distance of $3.3$ kpc, inferred via association of the source with the GLIMPSE-C01 cluster, these fluxes correspond to an Eddington fraction of order $10^{-3}$ for an accreting neutron star of mass $M=1.4M_\odot$, or even lower for a more massive accretor. However, the source spectra exhibit strong relativistic reflection features, indicating the presence of an accretion disk which extends close to the accretor, for which we measure a high spin, $a=0.967\pm0.013$. In addition to a change in flux and spectral shape, we find evidence for other changes between the soft and hard states, including moderate disk truncation with the inner disk radius increasing from $R_\mathrm{in}\approx3\,R_\mathrm{g}$ to $R_\mathrm{in}\approx8\,R_\mathrm{g}$, narrow Fe emission whose centroid decreases from $6.8\pm0.1$ keV to $6.3 \pm 0.1$ keV, and an increase in low-frequency ($10^{-3}$-$10^{-1}$ Hz) variability. Due to the high spin we conclude that the source is likely to be a black hole rather than a neutron star, and we discuss physical interpretations of the low apparent luminosity as well as the narrow Fe emission.Comment: 19 pages, 9 figures, 3 tables. Accepted for publication in Ap

Probing the nature of the low state in the extreme ultraluminous X-ray pulsar NGC 5907 ULX1

NGC 5907 ULX1 is the most luminous ultra-luminous X-ray pulsar (ULXP) known to date, reaching luminosities in excess of 1e41 erg/s. The pulsar is known for its fast spin-up during the on-state. Here, we present a long-term monitoring of the X-ray flux and the pulse period between 2003-2022. We find that the source was in an off- or low-state between mid-2017 to mid-2020. During this state, our pulse period monitoring shows that the source had spun down considerably. We interpret this spin-down as likely being due to the propeller effect, whereby accretion onto the neutron star surface is inhibited. Using state-of-the-art accretion and torque models, we use the spin-up and spin-down episodes to constrain the magnetic field. For the spin-up episode, we find solutions for magnetic field strengths of either around 1e12G or 1e13G, however, the strong spin-down during the off-state seems only to be consistent with a very high magnetic field, namely, >1e13G. This is the first time a strong spin-down is seen during a low flux state in a ULXP. Based on the assumption that the source entered the propeller regime, this gives us the best estimate so far for the magnetic field of NGC 5907 ULX1.Comment: 10 pages, 1 figure, accepted for publication in A&

PINT: A Modern Software Package for Pulsar Timing

Over the past few decades, the measurement precision of some pulsar-timing experiments has advanced from ~10 us to ~10 ns, revealing many subtle phenomena. Such high precision demands both careful data handling and sophisticated timing models to avoid systematic error. To achieve these goals, we present PINT (PINT Is Not Tempo3), a high-precision Python pulsar timing data analysis package, which is hosted on GitHub and available on Python Package Index (PyPI) as pint-pulsar. PINT is well-tested, validated, object-oriented, and modular, enabling interactive data analysis and providing an extensible and flexible development platform for timing applications. It utilizes well-debugged public Python packages (e.g., the NumPy and Astropy libraries) and modern software development schemes (e.g., version control and efficient development with git and GitHub) and a continually expanding test suite for improved reliability, accuracy, and reproducibility. PINT is developed and implemented without referring to, copying, or transcribing the code from other traditional pulsar timing software packages (e.g., TEMPO and TEMPO2) and therefore provides a robust tool for cross-checking timing analyses and simulating pulse arrival times. In this paper, we describe the design, usage, and validation of PINT, and we compare timing results between it and TEMPO and TEMPO2.Comment: Re-submitted to the Astrophysical Journal at December 31st, 202