Electrophysiology of glioma: a Rho GTPase-activating protein reduces tumor growth and spares neuron structure and function

Background. Glioblastomas are the most aggressive type of brain tumor. A successful treatment should aim at halting tumor growth and protecting neuronal cells to prevent functional deficits and cognitive deterioration. Here, we exploited a Rho GTPase-activating bacterial protein toxin, cytotoxic necrotizing factor 1 (CNF1), to interfere with glioma cell growth in vitro and vivo. We also investigated whether this toxin spares neuron structure and function in peritumoral areas. Methods. We performed a microarray transcriptomic and in-depth proteomic analysis to characterize the molecular changes triggered by CNF1 in glioma cells. We also examined tumor cell senescence and growth in vehicle-and CNF1-treated glioma-bearing mice. Electrophysiological and morphological techniques were used to investigate neuronal alterations in peritumoral cortical areas. Results. Administration of CNF1 triggered molecular and morphological hallmarks of senescence in mouse and human glioma cells in vitro. CNF1 treatment in vivo induced glioma cell senescence and potently reduced tumor volumes. In peritumoral areas of glioma-bearing mice, neurons showed a shrunken dendritic arbor and severe functional alterations such as increased spontaneous activity and reduced visual responsiveness. CNF1 treatment enhanced dendritic length and improved several physiological properties of pyramidal neurons, demonstrating functional preservation of the cortical network. Conclusions. Our findings demonstrate that CNF1 reduces glioma volume while at the same time maintaining the physiological and structural properties of peritumoral neurons. These data indicate a promising strategy for the development of more effective antiglioma therapies

The lively accretion disk in NGC 2992. I. Transient iron K emission lines in the high flux state

We report on one of the brightest flux levels of the Seyfert 2 galaxy NGC 2992 ever observed in X-rays, on May 2019. The source has been monitored every few days from March 26, 2019 to December 14, 2019 by Swift-XRT, and simultaneous XMM-Newton (250 ks) and NuSTAR (120 ks) observations were triggered on May 6, 2019. The high count rate of the source (its 2-10 keV flux ranged between 0.7 and $1.0\times10^{-10}$ erg cm$^{-2}$ s$^{-1}$) allows us to perform a time-resolved spectroscopy, probing spatial scales of tens of gravitational radii from the central black hole. By constructing a map of the excess emission over the primary continuum, we find several emission structures in the 5.0-7.2 keV energy band. From fitting the 50 EPIC pn spectral slices of $\sim$5 ks duration, we interpret them as a constant narrow iron K$\alpha$ line and three variable components in the iron K complex. When a self-consistent model accounting for the accretion disk emission is considered (KYNrline), two of these features (in the 5.0-5.8 keV and 6.8-7.2 keV bands) can be ascribed to a flaring region of the accretion disk located at ${r_{in}}\simeq15$-40 r$_{g\rm }$ from the black hole. The third one (6.5-6.8 keV) is likely produced at much larger radii ($r_{in}>50$ r$_{g\rm }$). The inner radius and the azimuthal extension retrieved from the coadded spectra of the flaring states are ${ r_{in}}=15\pm3$ r$_{g\rm }$ and $\phi=165^{\circ}-330^{\circ}$, suggesting that the emitting region responsible for the broad iron K component is a relatively compact annular sector within the disk. Our findings support a physical scenario in which the accretion disk in NGC 2992 becomes more active at high accretion rates ($L_{\rm bol}/L_{\rm Edd}\geq4\%$).Comment: 12 pages, 12 figures, 1 table. Accepted for publication in MNRA

X-ray spectroscopic survey of highly accreting AGN

Improving our understanding of the nuclear properties of high-Eddington-ratio (λEdd) active galactic nuclei (AGN) is necessary since at this regime the radiation pressure is expected to affect the structure and efficiency of the accretion disc-corona system. This may cause departures from the typical nuclear properties of low-λEdd AGN, which have been largely studied so far. We present here the X-ray spectral analysis of 14 radio-quiet, λEdd ≥ 1 AGN at 0.4 ≤ z ≤ 0.75, observed with XMM-Newton. Optical/UV data from simultaneous Optical Monitor observations have also been considered. These quasars were selected to have relatively high values of black hole mass (MBH ~ 108-8.5 M⊙) and bolometric luminosity (Lbol ~ 1046 erg s-1) in order to complement previous studies of high- λEdd AGN at lower MBH and Lbol. We studied the relation between λEdd and other key X-ray spectral parameters, such as the photon index (Γ) of the power-law continuum, the X-ray bolometric correction (kbol,X), and the optical/UV-to-X-ray spectral index (αox). Our analysis reveals that, despite the homogeneous optical and supermassive black hole accretion properties, the X-ray properties of these high-λEdd AGN are quite heterogeneous. We indeed measured values of Γ between 1.3 and 2.5, at odds with the expectations based on previously reported Γ-λEdd relations, for which Γ ≥ 2 would be a ubiquitous hallmark of AGN with λEdd ~ 1. Interestingly, we found that ~30% of the sources are X-ray weak, with an X-ray emission about a factor of ~10-80 fainter than that of typical AGN at similar UV luminosities. The X-ray weakness seems to be intrinsic and not due to the presence of absorption along the line of sight to the nucleus. This result may indicate that high-λEdd AGN commonly undergo periods of intrinsic X-ray weakness. Furthermore, results from follow-up monitoring with Swift of one of these X-ray weak sources suggest that these periods can last for several years

Open Universe for Blazars: A new generation of astronomical products based on 14 years of Swift -XRT data

Aims. Open Universe for Blazars is a set of high-transparency multi-frequency data products for blazar science, and the tools designed to generate them. Blazars are drawing growing interest following the consolidation of their position as the most abundant type of source in the extragalactic very high-energy γ-ray sky, and because of their status as prime candidate sources in the nascent field of multi-messenger astrophysics. As such, blazar astrophysics is becoming increasingly data driven, depending on the integration and combined analysis of large quantities of data from the entire span of observational astrophysics techniques. The project was therefore chosen as one of the pilot activities within the United Nations Open Universe Initiative, whose objective is to stimulate a large increase in the accessibility and ease of utilisation of space science data for the worldwide benefit of scientific research, education, capacity building, and citizen science. Methods. Our aim is to deliver innovative data science tools for multi-messenger astrophysics. In this work we report on a data analysis pipeline called Swift-DeepSky based on the Swift XRTDAS software and the XIMAGE package, encapsulated into a Docker container. Swift-DeepSky downloads and reads low-level data, generates higher level products, detects X-ray sources, and estimates several intensity and spectral parameters for each detection, thus facilitating the generation of complete and up-to-date science-ready catalogues from an entire space-mission data set. Results. As a first application of our innovative approach, we present the results of a detailed X-ray image analysis based on Swift-DeepSky that was run on all Swift-XRT observations including a known blazar, carried out during the first 14 years of operations of the Neil Gehrels Swift Observatory. Short exposures executed within one week of each other have been added to increase sensitivity, which ranges between ∼1 × 10-12 and ∼1 × 10-14 erg cm-2 s-1 (0.3-10.0 keV). After cleaning for problematic fields, the resulting database includes over 27 000 images integrated in different X-ray bands, and a catalogue, called 1OUSXB, that provides intensity and spectral information for 33 396 X-ray sources, 8896 of which are single or multiple detections of 2308 distinct blazars. All the results can be accessed online in a variety of ways, from the Open Universe portal through Virtual Observatory services, via the VOU-Blazar tool and the SSDC SED builder. One of the most innovative aspects of this work is that the results can be easily reproduced and extended by anyone using the Docker version of the Swift-DeepSky pipeline, which runs on Linux, Mac, and Windows machines, and does not require any specific experience in X-ray data analysis.Fil: Giommi, Paolo. Università di Roma; Italia. International Center For Relativistic Astrophysics; Italia. Universitat Technical Zu Munich; AlemaniaFil: Brandt, C. H.. International Center For Relativistic Astrophysics; Italia. Jacobs University; AlemaniaFil: Barres de Almeida, U.. International Center For Relativistic Astrophysics; Italia. Centro Brasileiro de Pesquisas Físicas; BrasilFil: Pollock, A. M. T.. University of Sheffield; Reino UnidoFil: Arneodo, F.. New York University Abu Dhabi; Arabia SauditaFil: Chang, Y. L.. International Center For Relativistic Astrophysics; ItaliaFil: Civitarese, Enrique Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: de Angelis, Maria Cruz. Università di Roma; ItaliaFil: D'Elia, V.. Space Science Data Center; Italia. Osservatorio Astronomico di Roma; ItaliaFil: Del Rio Vera, J.. United Nations Office for Outer Space Affairs; AustraliaFil: Di Pippo, S.. United Nations Office for Outer Space Affairs; AustraliaFil: Middei, Riccardo. Università di Roma; ItaliaFil: Penacchioni, Ana Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Perri, M.. Osservatorio Astronomico di Roma; Italia. Space Science Data Center; ItaliaFil: Ruffini, Remo. International Center For Relativistic Astrophysics; ItaliaFil: Sahakyan, Narek. International Centre For Relativistic Astrophysics Network; ArmeniaFil: Turriziani, Sara. Computational Astrophysics Laboratory; Japó

The Open Universe survey of Swift-XRT GRB fields: a complete sample of HBL blazars

We have analysed all the X-ray images centred on Gamma Ray Bursts generated by Swift over the last 15 years using automatic tools that do not require any expertise in X-ray astronomy, producing results in excellent agreement with previous findings. This work, besides presenting the largest medium-deep survey of the X-ray sky and a complete sample of blazars, wishes to be a step in the direction of achieving the ultimate goal of the Open Universe Initiative, that is to enable non expert people to fully benefit of space science data, possibly extending the potential for scientific discovery, currently confined within a small number of highly specialised teams, to a much larger population. We have used the Swift_deepsky Docker container encapsulated pipeline to build the largest existing flux-limited and unbiased sample of serendipitous X-ray sources. Swift_deepsky runs on any laptop or desktop computer with a modern operating system. The tool automatically downloads the data and the calibration files from the archives, runs the official Swift analysis software and produces a number of results including images, the list of detected sources, X-ray fluxes, SED data, and spectral slope estimations. We used our source list to build the LogN-LogS of extra-galactic sources, which perfectly matches that estimated by other satellites. Combining our survey with multi-frequency data we selected a complete radio flux-density limited sample of High Energy Peaked (HBL) blazars.Comment: Accepted for publication in A&A. 8 pages, 7 figure

HYPerluminous quasars at the Epoch of ReionizatION (HYPERION). A new regime for the X-ray nuclear properties of the first quasars

The existence of luminous quasars (QSO) at the Epoch of Reionization (EoR; i.e. z>6) powered by supermassive black holes (SMBH) with masses $\gtrsim10^9~M_\odot$ challenges models of early SMBH formation. To shed light on the nature of these sources we started a multiwavelength programme based on a sample of 18 HYPerluminous quasars at the Epoch of ReionizatION (HYPERION). These are the luminous QSOs whose SMBH must have had the fastest mass growth during the Universe first Gyr. In this paper we present the HYPERION sample and report on the first of the 3 years planned observations of the 2.4 Ms XMM-Newton Multi-Year Heritage program on which HYPERION is based. The goal of this program is to accurately characterize the X-ray nuclear properties of QSOs at the EoR. Through a joint X-ray spectral analysis of 10 sources, in the rest-frame $\sim2-50$ keV range, we report a steep average photon index ($\Gamma\sim2.4\pm0.1$). Absorption is not required. The average $\Gamma$ is inconsistent at $\geq4\sigma$ level with the canonical 1.8-2 value measured in QSO at z<6. This spectral slope is also much steeper than that reported in lower-z QSOs with similar luminosity or accretion rate, thus suggesting a genuine redshift evolution. Alternatively, we can interpret this result as the presence of an unusually low-energy cutoff $E_{cut}\sim20$ keV on a standard $\Gamma=1.9$ power-law. We also report on mild indications that HYPERION QSOs show higher soft X-ray emission at 2 keV compared to the UV one at 2500A than expected by lower-z luminous AGN. We speculate that a redshift-dependent coupling between the corona and accretion disc or intrinsically different coronal properties may account for the steep spectral slopes, especially in the presence of powerful winds. The reported slopes, if confirmed at lower luminosities, may have an important impact on future X-ray AGN studies in the early Universe.Comment: 21 pages (including appendix), 12 figures, 4 tables. Accepted for pubblication in A&

Multi-wavelength campaign on NGC 7469. IV. The broad-band X-ray spectrum

We conducted a multi-wavelength 6-month campaign to observe the Seyfert Galaxy NGC 7469, using the space-based observatories HST, Swift, XMM-Newton and NuSTAR. We report the results of the spectral analysis of the seven simultaneous XMM-Newton and NuSTAR observations. The source shows significant flux variability within each observation, but the average flux is less variable among the different pointings of our campaign. Our spectral analysis reveals a prominent narrow neutral Fe Kαemission line in all the spectra and weaker contributions from Fe Kβ, neutral Ni Kα, and ionized iron. We find no evidence for variability or relativistic effects acting on the emission lines, which indicates that they originate from distant material. In the joint analysis of XMM-Newton and NuSTAR data, a constant photon index is found (Γ = 1.78 ± 0.02) together with a high energy cut-off E_(cut) = 170_(−40)^(+60) keV. Adopting a self-consistent Comptonization model, these values correspond to an average coronal electron temperature of kT = 45_(−12)^(+15) keV and, assuming a spherical geometry, an optical depth τ = 2.6 ± 0.9. The reflection component is consistent with being constant and the reflection fraction is in the range R = 0.3−0.6. A prominent soft excess dominates the spectra below 4 keV. This is best fit with a second Comptonization component, arising from a warm corona with an average kT = 0.67 ± 0.03 keV and a corresponding optical depth τ = 9.2 ± 0.2

A new emulated Monte Carlo radiative transfer disc-wind model: X-Ray Accretion Disc-wind Emulator – XRADE

Abstract We present a new X-Ray Accretion Disk-wind Emulator (xrade) based on the 2.5D Monte Carlo radiative transfer code which provides a physically-motivated, self-consistent treatment of both absorption and emission from a disk-wind by computing the local ionization state and velocity field within the flow. xrade is then implemented through a process that combines X-ray tracing with supervised machine learning. We develop a novel emulation method consisting in training, validating, and testing the simulated disk-wind spectra into a purposely built artificial neural network. The trained emulator can generate a single synthetic spectrum for a particular parameter set in a fraction of a second, in contrast to the few hours required by a standard Monte Carlo radiative transfer pipeline. The emulator does not suffer from interpolation issues with multi-dimensional spaces that are typically faced by traditional X-ray fitting packages such as xspec. xrade will be suitable to a wide number of sources across the black-hole mass, ionizing luminosity, and accretion rate scales. As an example, we demonstrate the applicability of xrade to the physical interpretation of the X-ray spectra of the bright quasar PDS 456, which hosts the best-established accretion-disk wind observed to date. We anticipate that our emulation method will be an indispensable tool for the development of high-resolution theoretical models, with the necessary flexibility to be optimized for the next generation micro-calorimeters on board future missions, like XRISM/Resolve and Athena/X-IFU. This tool can also be implemented across a wide variety of X-ray spectral models and beyond

Multi-wavelength campaign on NCG 7469 IV. The broad-band X-ray spectrum

We conducted a multi-wavelength 6-month campaign to observe the Seyfert Galaxy NGC 7469, using the space-based observatories HST, Swift, XMM-Newton and NuSTAR. We report the results of the spectral analysis of the seven simultaneous XMM-Newton and NuSTAR observations. The source shows significant flux variability within each observation, but the average flux is less variable among the different pointings of our campaign. Our spectral analysis reveals a prominent narrow neutral Fe Kα emission line in all the spectra and weaker contributions from Fe Kβ, neutral Ni Kα, and ionized iron. We find no evidence for variability or relativistic effects acting on the emission lines, which indicates that they originate from distant material. In the joint analysis of XMM-Newton and NuSTAR data, a constant photon index is found (Γ = 1.78 ± 0.02) together with a high energy cut-off Ecut = 170+ − 60 40 keV. Adopting a self-consistent Comptonization model, these values correspond to an average coronal electron temperature of kT = 45+ − 15 12 keV and, assuming a spherical geometry, an optical depth τ = 2.6 ± 0.9. The reflection component is consistent with being constant and the reflection fraction is in the range R = 0.3−0.6. A prominent soft excess dominates the spectra below 4 keV. This is best fit with a second Comptonization component, arising from a warm corona with an average kT = 0.67 ± 0.03 keV and a corresponding optical depth τ = 9.2 ± 0.2