X-ray reflection from the inner disc of the AGN Ton S180

We analyse a long archival XMM-Newton observation of the narrow-line Seyfert 1 galaxy Ton S180, using the latest reflection models to explore the high quality X-ray spectrum. We find that the iron line is relatively narrow and sharp, and the soft excess is extremely smooth. We cannot find an acceptable reflection model that describes both components, and conclude that the soft excess cannot be produced by relativistic reflection. Fitting the 3-10 keV band with relativistic reflection to model the iron line strongly prefers low spin values (< 0.4), with the exact value depending on the model and not well constrained. We then model the broad- band spectrum with a two-component Comptonization continuum plus relativistic reflection. This gives a much better fit than a pure reflection model, which again prefers a low spin value. The photon index of the reflection component is intermediate between the two Comptoniza- tion components, suggesting that both illuminate the disk a similar amount and therefore both contribute to the reflection

Using principal component analysis to understand the variability of PDS 456

We present a spectral-variability analysis of the low-redshift quasar PDS 456 using principal component analysis. In the XMM-Newton data, we find a strong peak in the first principal component at the energy of the Fe absorption line from the highly blueshifted outflow. This indicates that the absorption feature is more variable than the continuum, and that it is responding to the continuum. We find qualitatively different behaviour in the Suzaku data, which is dominated by changes in the column density of neutral absorption. In this case, we find no evidence of the absorption produced by the highly ionized gas being correlated with this variability. Additionally, we perform simulations of the source variability, and demonstrate that PCA can trivially distinguish between outflow variability correlated, anti-correlated, and un-correlated with the continuum flux. Here, the observed anti-correlation between the absorption line equivalent width and the continuum flux may be due to the ionization of the wind responding to the continuum. Finally, we compare our results with those found in the narrow-line Seyfert 1 IRAS 13224-3809. We find that the Fe K UFO feature is sharper and more prominent in PDS 456, but that it lacks the lower energy features from lighter elements found in IRAS 13224-3809, presumably due to differences in ionization

Assessment of a novel, capsid-modified adenovirus with an improved vascular gene transfer profile

&lt;p&gt;Background: Cardiovascular disorders, including coronary artery bypass graft failure and in-stent restenosis remain significant opportunities for the advancement of novel therapeutics that target neointimal hyperplasia, a characteristic of both pathologies. Gene therapy may provide a successful approach to improve the clinical outcome of these conditions, but would benefit from the development of more efficient vectors for vascular gene delivery. The aim of this study was to assess whether a novel genetically engineered Adenovirus could be utilised to produce enhanced levels of vascular gene expression.&lt;/p&gt; &lt;p&gt;Methods: Vascular transduction capacity was assessed in primary human saphenous vein smooth muscle and endothelial cells using vectors expressing the LacZ reporter gene. The therapeutic capacity of the vectors was compared by measuring smooth muscle cell metabolic activity and migration following infection with vectors that over-express the candidate therapeutic gene tissue inhibitor of matrix metalloproteinase-3 (TIMP-3).&lt;/p&gt; &lt;p&gt;Results: Compared to Adenovirus serotype 5 (Ad5), the novel vector Ad5T*F35++ demonstrated improved binding and transduction of human vascular cells. Ad5T*F35++ mediated expression of TIMP-3 reduced smooth muscle cell metabolic activity and migration in vitro. We also demonstrated that in human serum samples pre-existing neutralising antibodies to Ad5T*F35++ were less prevalent than Ad5 neutralising antibodies.&lt;/p&gt; &lt;p&gt;Conclusions: We have developed a novel vector with improved vascular transduction and improved resistance to human serum neutralisation. This may provide a novel vector platform for human vascular gene transfer.&lt;/p&gt

Discovery of an ~2-h high-frequency X-ray QPO and iron Kα reverberation in the active galaxy MS 2254.9-3712

We report the discovery of a $\sim 1.5 \times 10^{-4}$ Hz ($\sim 2$ hr) X-ray quasi-periodic oscillation (QPO) in the active galaxy MS 2254.9-3712, using a $\sim 70$ ks XMM-Newton observation. The QPO is significantly detected ($\sim 3.3 \sigma$) in the $1.2 - 5.0$ keV band only, connecting its origin with the primary X-ray power-law continuum. We detect a highly coherent soft lag between the $0.3 - 0.7$ keV and $1.2 - 5.0$ keV energy bands at the QPO frequency and at a frequency band in a 3:2 ratio, strongly suggesting the presence of a QPO harmonic. An iron K$\alpha$ reverberation lag is found at the harmonic frequency, indicating the reflecting material subtends some angle to the primary continuum, which is modulated by the QPO mechanism. Frequency resolved spectroscopy reveals the QPO and harmonic to have a hard energy dependence. These properties of the QPO variability, together with the current black hole mass estimate, $M_{\rm bh} \sim 4 \times 10^{6} M_{\rm sun}$, are consistent with the QPO originating from the same process as the high frequency QPO phenomenon observed in black hole X-ray binaries. Principle component analysis reveals the spectral variability in MS 2254.9-3712 is similar to that of the active galaxy RE J1034+396, a source which also displays an X-ray QPO. This suggests a distinct spectral variability pattern for accreting black holes when in a state where QPOs are present

X-ray lags in PDS 456 revealed by Suzaku observations

X-ray reverberation lags from the vicinity of supermassive black holes have been detected in almost 30 active galactic nuclei (AGNs). The soft lag, which is the time delay between the hard and soft X-ray light curves, is usually interpreted as the time difference between the direct and reflected emission, but is alternatively suggested to arise from the direct and scattering emission from distant clouds. By analysing the archival Suzaku observations totalling an exposure time of ∼770 ks, we discover a soft lag of 10 ± 3.4 ks at 9.58 × 10−6 Hz in the luminous quasar PDS 456, which is the longest soft lag and lowest Fourier frequency reported to date. In this study, we use the maximum likelihood method to deal with non-continuous nature of the Suzaku light curves. The result follows the mass–scaling relation for soft lags, which further supports that soft lags originate from the innermost areas of AGNs and hence are best interpreted by the reflection scenario. Spectral analysis has been performed in this work and we find no evidence of clumpy partial-covering absorbers. The spectrum can be explained by a self-consistent relativistic reflection model with warm absorbers, and spectral variations over epochs can be accounted for by the change of the continuum, and of column density and ionization states of the warm absorbers.EMC gratefully acknowledges support from the NSF through CAREER award number AST-1351222. CSR thanks NASA for support under grant NNX15AU54G. ACF acknowledges ERC Advanced Grant 340442

Revealing the ultrafast outflow in IRAS 13224-3809 through spectral variability

We present an analysis of the long-term X-ray variability of the extreme narrow-line Seyfert 1 (NLS1) galaxy IRAS 13224-3809 using principal component analysis (PCA) and fractional excess variability (Fvar) spectra to identify model-independent spectral components. We identify a series of variability peaks in both the first PCA component and Fvar spectrum which correspond to the strongest predicted absorption lines from the ultra-fast outflow (UFO) discovered by Parker et al. (2017). We also find higher order PCA components, which correspond to variability of the soft excess and reflection features. The subtle differences between RMS and PCA results argue that the observed flux-dependence of the absorption is due to increased ionization of the gas, rather than changes in column density or covering fraction. This result demonstrates that we can detect outflows from variability alone, and that variability studies of UFOs are an extremely promising avenue for future research

Broadband Observations of High Redshift Blazars

We present a multi-wavelength study of four high redshift blazars, S5 0014+81 (z = 3.37), CGRaBS J0225+1846 (z = 2.69), BZQ J1430+4205 (z = 4.72), and 3FGL J1656.2−3303 (z = 2.40) using quasi-simultaneous data from the Swift, Nuclear Spectroscopic Telescope Array (NuSTAR) and the Fermi-Large Area Telescope (LAT) and also archival XMM-Newton observations. Other than 3FGL J1656.2−3303, none of the sources were known as γ-ray emitters, and our analysis of ~7.5 yr of LAT data reveals the first time detection of statistically significant γ-ray emission from CGRaBS J0225+1846. We generate the broadband spectral energy distributions (SED) of all the objects, centering at the epoch of NuSTAR observations and reproduce them using a one-zone leptonic emission model. The optical−UV emission in all the objects can be explained by radiation from the accretion disk, whereas the X-ray to γ-ray windows of the SEDs are found to be dominated by inverse Compton scattering off the broad line region photons. All of them host black holes that are billions of solar masses. Comparing the accretion disk luminosity and the jet power of these sources with a large sample of blazars, we find them to occupy a high disk luminosity–jet power regime. We also investigate the X-ray spectral properties of the sources in detail with a major focus on studying the causes of soft X-ray deficit, a feature generally seen in high redshift radio-loud quasars. We summarize that this feature could be explained based on the intrinsic curvature in the jet emission rather than being due to the external effects predicted in earlier studies, such as host galaxy and/or warm absorption.A.C.F. thanks Greg Madejski for discussions on the curvature of blazar X-ray spectra and acknowledges support from ERC Advanced Grant 340442. This research has made use of data, software, and/or web tools obtained from NASAs High Energy Astrophysics Science Archive Research Center (HEASARC), a service of Goddard Space Flight Center and the Smithsonian Astrophysical Observatory. Part of this work is based on archival data, software, or online services provided by the ASI Science Data Center (ASDC). This research has made use of the XRT Data Analysis Software (XRTDAS) developed under the responsibility of the ASDC, Italy. This research has also made use of the NuSTAR Data Analysis Software (NuSTARDAS) jointly developed by the ASI Science Data Center (ASDC, Italy) and the California Institute of Technology (Caltech, USA). This research has made use of the NASA/IPAC Extragalactic Database (NED) which is operated by the Jet Propulsion Laboratory, California Institute of Technology, under contract with the National Aeronautics and Space Administration. Funding for SDSS-III has been provided by the Alfred P. Sloan Foundation, the Participating Institutions, the National Science Foundation, and the U.S. Department of Energy Office of Science. The SDSS-III web site is http://www.sdss3.org/

In vitro and in vivo evaluation of human adenovirus type 49 as a vector for therapeutic applications

The human adenovirus phylogenetic tree is split across seven species (A–G). Species D adenoviruses offer potential advantages for gene therapy applications, with low rates of pre-exist-ing immunity detected across screened populations. However, many aspects of the basic virology of species D—such as their cellular tropism, receptor usage, and in vivo biodistribution profile— remain unknown. Here, we have characterized human adenovirus type 49 (HAdV-D49)—a rela-tively understudied species D member. We report that HAdV-D49 does not appear to use a single pathway to gain cell entry, but appears able to interact with various surface molecules for entry. As such, HAdV-D49 can transduce a broad range of cell types in vitro, with variable engagement of blood coagulation FX. Interestingly, when comparing in vivo biodistribution to adenovirus type 5, HAdV-D49 vectors show reduced liver targeting, whilst maintaining transduction of lung and spleen. Overall, this presents HAdV-D49 as a robust viral vector platform for ex vivo manipulation of human cells, and for in vivo applications where the therapeutic goal is to target the lung or gain access to immune cells in the spleen, whilst avoiding liver interactions, such as intravascular vaccine applications