Nucleosome-CHD4 chromatin remodeller structure maps human disease mutations

Chromatin remodelling plays important roles in gene regulation during development, differentiation and in disease. The chromatin remodelling enzyme CHD4 is a component of the NuRD and ChAHP complexes that are involved in gene repression. Here we report the cryo-electron microscopy (cryo-EM) structure of Homo sapiens CHD4 engaged with a nucleosome core particle in the presence of the non-hydrolysable ATP analogue AMP-PNP at an overall resolution of 3.1 Å. The ATPase motor of CHD4 binds and distorts nucleosomal DNA at superhelical location (SHL) +2, supporting the 'twist defect' model of chromatin remodelling. CHD4 does not induce unwrapping of terminal DNA, in contrast to its homologue Chd1, which functions in gene activation. Our structure also maps CHD4 mutations that are associated with human cancer or the intellectual disability disorder Sifrim-Hitz-Weiss syndrome

Resonance modes in a 1D medium with two purely resistive boundaries: calculation methods, orthogonality and completeness

Studying the problem of wave propagation in media with resistive boundaries can be made by searching for "resonance modes" or free oscillations regimes. In the present article, a simple case is investigated, which allows one to enlighten the respective interest of different, classical methods, some of them being rather delicate. This case is the 1D propagation in a homogeneous medium having two purely resistive terminations, the calculation of the Green function being done without any approximation using three methods. The first one is the straightforward use of the closed-form solution in the frequency domain and the residue calculus. Then the method of separation of variables (space and time) leads to a solution depending on the initial conditions. The question of the orthogonality and completeness of the complex-valued resonance modes is investigated, leading to the expression of a particular scalar product. The last method is the expansion in biorthogonal modes in the frequency domain, the modes having eigenfrequencies depending on the frequency. Results of the three methods generalize or/and correct some results already existing in the literature, and exhibit the particular difficulty of the treatment of the constant mode

Long-term optical, UV, and X-ray continuum variations in the changing-look AGN HE 1136-2304

A strong outburst in the X-ray continuum and a change of its Seyfert spectral type was detected in HE 1136-2304 in 2014. The spectral type changed from nearly Seyfert 2 type (1.95) to Seyfert 1.5 type in comparison to previous observations taken ten to twenty years before. In a subsequent variability campaign we wanted to investigate whether this outburst was a single event or whether the variability pattern following the outburst was similar to those seen in other variable Seyfert galaxies. In addition to a SALT spectral variability campaign, we carried out optical continuum as well as X-ray and UV (Swift) monitoring studies from 2014 to 2017. HE 1136-2304 strongly varied on timescales of days to months from 2014 to 2017. No systematic trends were found in the variability behavior following the outburst in 2014. A general decrease in flux would have been expected for a tidal disruption event. This could not be confirmed. More likely the flux variations are connected to irregular fluctuations in the accretion rate. The strongest variability amplitudes have been found in the X-ray regime: HE 1136-2304 varied by a factor of eight during 2015. The amplitudes of the continuum variability (from the UV to the optical) systematically decreased with wavelength following a power law F_var = a ${\times}$ {\lambda}^-c with c = 0.84. There is a trend that the B-band continuum shows a delay of three light days with respect to the variable X-ray flux. The Seyfert type 1.5 did not change despite the strong continuum variations for the period between 2014 and 2017.Comment: 25 pages, 21 figures, Astronomy & Astrophysics in pres

Broad-line region structure and line profile variations in the changing look AGN HE1136-2304

A strong X-ray outburst was detected in HE1136-2304 in 2014. Accompanying optical spectra revealed that the spectral type has changed from a nearly Seyfert 2 type (1.95), classified by spectra taken 10 and 20 years ago, to a Seyfert 1.5 in our most recent observations. We seek to investigate a detailed spectroscopic campaign on the spectroscopic properties and spectral variability behavior of this changing look AGN and compare this to other variable Seyfert galaxies. We carried out a detailed spectroscopic variability campaign of HE1136-2304 with the 10 m Southern African Large Telescope (SALT) between 2014 December and 2015 July. The broad-line region (BLR) of HE1136-2304 is stratified with respect to the distance of the line-emitting regions. The integrated emission line intensities of Halpha, Hbeta, HeI 5876, and HeII 4686 originate at distances of 15.0 (+4.2,-3.8), 7.5 (+4.6,-5.7), 7.3 (+2.8,-4.4), and 3.0 (+5.3,-3.7) light days with respect to the optical continuum at 4570AA. The variability amplitudes of the integrated emission lines are a function of distance to the ionizing continuum source as well. We derived a central black hole mass of 3.8 (+-3.1) 10exp(7) M_solar based on the line widths and distances of the BLR. The outer line wings of all BLR lines respond much faster to continuum variations indicating a Keplerian disk component for the BLR. The response in the outer wings is about two light days shorter than the response of the adjacent continuum flux with respect to the ionizing continuum flux. The vertical BLR structure in HE1136-2304 confirms a general trend that the emission lines of narrow line active galactic nuclei (AGNs) originate at larger distances from the midplane in comparison to AGNs showing broader emission lines. Otherwise, the variability behavior of this changing look AGN is similar to that of other AGN.Comment: 21 pages, 33 figure

Noise Characteristics of a Four-Jet Impingement Device Inside a Broadband Engine Noise Simulator

The noise generation mechanisms for four directly impinging supersonic jets are investigated employing implicit large eddy simulations with a higher-order accurate weighted essentially non-oscillatory shock-capturing scheme. Impinging jet devices are often used as an experimental apparatus to emulate a broadband noise source. Although such devices have been used in many experiments, a detailed investigation of the noise generation mechanisms has not been conducted before. Thus, the underlying physical mechanisms that are responsible for the generation of sound waves are not well understood. The flow field is highly complex and contains a wide range of temporal and spatial scales relevant for noise generation. Proper orthogonal decomposition of the flow field is utilized to characterize the unsteady nature of the flow field involving unsteady shock oscillations, large coherent turbulent flow structures, and the sporadic appearance of vortex tubes in the center of the impingement region. The causality method based on Lighthill's acoustic analogy is applied to link fluctuations of flow quantities inside the source region to the acoustic pressure in the far field. It will be demonstrated that the entropy fluctuation term in the Lighthill's stress tensor plays a vital role in the noise generation process. Consequently, the understanding of the noise generation mechanisms is employed to develop a reduced-order linear acoustic model of the four-jet impingement device. Finally, three linear acoustic FJID models are used as broadband noise sources inside an engine nacelle and the acoustic scattering results are validated against far-field acoustic experimental data

Levy stable distribution and [0,2] power law dependence of acoustic absorption on frequency

The absorption of acoustic wave propagation in a broad variety of lossy media is characterized by an empirical power law function of frequency, w^y. It has long been noted that exponent y ranges from 0 to 2 for diverse media. Recently, the present author developed a fractional Laplacian wave equation to accurately model the power law dissipation, which can be further reduced to the fractional Laplacian diffusion equation. The latter is known underlying the Levy stable distribution theory. Consequently, the parameters y is found to be the Levy stability index, which is known bounded within 0<y\le2. This finding first provides a theoretical explanation of empirical observations 0<y<=2. Statistically, the frequency-dependent absorption can thus be understood a Levy stable process, where the parameter y describes the fractal nature of attenuative media.Comment: Welcome any comments to [email protected]

A galaxy cluster in the innermost Zone of Avoidance, close to the radio phoenix VLSS J2217.5+5943

Context. Galaxy clusters grow via mergers with other clusters and groups. Extended regions of diffuse radio emission with a steep radio spectral index are thought to be indicators of such merger events. Extended radio sources with a significantly curved spectrum and a complex morphology have been found in several galaxy clusters. It has been proposed that these so-called radio phoenices are witnesses of cluster mergers and of the presence of active galactic nuclei prior to the merger. Shock fronts or turbulence induced by the mergers are believed to reenergize plasma emitted in the past active phase of a galaxy. Aims. The steep spectrum radio source VLSS J2217.5+5943 shows a complex filamentary morphology and a curved spectrum. Therefore, the source has previously been classified as a radio phoenix. However, no galaxy cluster associated with this radio source had confidently been detected until now because the source is located in the direction of the innermost zone of the Galactic plane at b = +2.4°, the innermost Zone of Avoidance (ZoA). The main aim of this work is to identify galaxies that are part of a cluster at the location of VLSS J2217.5+5943, determine their redshifts, and analyze their connection with the radio source. The confirmation of a cluster would corroborate the classification of the radio source as a radio phoenix and demonstrate that extended, diffuse radio sources are useful indicators of the presence of a galaxy cluster, in particular in the innermost ZoA. Methods. We analyzed archival observations in the near infrared and mid infrared (Spitzer) to select the galaxies in the immediate neighborhood of the radio source. A sample of 23 galaxies were selected as candidate cluster members. Furthermore, we carried out deep integral field spectroscopy covering 6450 to 10 500 Å with the red unit of the Hobby-Eberly Telescope second generation low resolution spectrograph (LRS2-R). We also reanalyzed archival GMRT observations at 325 and 610 MHz. Results. We selected 23 galaxies within a radius of 2.5 arcmin, centered on RA = 22$^h$17$^m$​.5, Dec = +59° 43′ (J2000). Spectra were obtained for three of the brightest galaxies. For two galaxies we derived redshifts of z = 0.165 and z = 0.161, based on NaD absorption and TiO band heads. Their spectra correspond to E-type galaxies. Both galaxies are spatially associated with VLSS J2217.5+5943. The spectrum of the third galaxy, which is slightly farther from the radio source, indicates a LINER spectral type at z = 0.042. It is apparently a foreground galaxy with respect to the cluster we identified. Conclusions. VLSS J2217.5+5943 is associated with a massive galaxy cluster at redshift z = 0.163 ± .003, supporting its classification as a radio phoenix. The intrinsic properties of the radio source, computed for the cluster redshift, are in good agreement with those of other known radio phoenices. The identification of the galaxy cluster demonstrates that far-red spectroscopy with LRS2-R succeeds in determining the redshift of galaxies in the innermost ZoA. Moreover, it confirms that radio sources can be useful indicators of the presence of galaxy clusters in the ZoA

GMRES implementations and residual smoothing techniques for solving ill-posed linear systems

AbstractThere are verities of useful Krylov subspace methods to solve nonsymmetric linear system of equations. GMRES is one of the best Krylov solvers with several different variants to solve large sparse linear systems. Any GMRES implementation has some advantages. As the solution of ill-posed problems are important. In this paper, some GMRES variants are discussed and applied to solve these kinds of problems. Residual smoothing techniques are efficient ways to accelerate the convergence speed of some iterative methods like CG variants. At the end of this paper, some residual smoothing techniques are applied for different GMRES methods to test the influence of these techniques on GMRES implementations

Changing-look NLS1 galaxies, their detection with SVOM, and the case of NGC 1566

We discuss applications of the study of the new and barely explored class of changing-look (CL) narrow-line Seyfert 1 (NLS1) galaxies and comment on their detection with the space mission SVOM (Space Variable Objects Monitor). We highlight the case of NGC 1566, which is outstanding in many respects, for instance as one of the nearest known CL AGN undergoing exceptional outbursts. Its NLS1 nature is discussed, and we take it as a nearby prototype for systems that could be discovered and studied in the near future, including with SVOM. Finally, we briefly examine the broader implications and applications of CL events in NLS1 galaxies and show that such systems, once discovered in larger numbers, will greatly advance our understanding of the physics of the environment of rapidly growing supermassive black holes. This White Paper is part of a sequence of publications which explore aspects of our understanding of (CL) NLS1 galaxy physics with future missions.Comment: 14 pages, 4 figures. Accepted for publication in the Universe Special Issue "A Multimessenger View of Supermassive Black Holes and the Quasar Main Sequence

Whole-genome sequencing reveals two prolonged simultaneous outbreaks involving Pseudomonas aeruginosa high-risk strains ST111 and ST235 with resistance to quaternary ammonium compounds

Objective Water-bearing systems are known as frequent Pseudomonas aeruginosa (PA) outbreak sources. However, many older buildings continue to have sanitary facilities in high-risk departments such as the ICU. We present two simultaneous prolonged multi-drug-resistant (MDR) PA outbreaks detected at the ICU of a pulmonology hospital, which were resolved by whole-genome sequencing (WGS). Methods Outbreak management and investigations were initiated in August 2019 after detecting two patients with nosocomial VIM-2-positive MDR PA. The investigations involved weekly patient screenings for four months and extensive environmental sampling for 15 months. All patient and environmental isolates were collected and analysed by WGS. Results From April to September 2019, we identified 10 patients with nosocomial MDR PA, including five VIM-2-positive strains. VIM-2-positive strains were also detected in nine sink drains, two toilets, and a cleaning bucket. WGS revealed that of 16 VIM-2-positive isolates, 14 were ST111 that carried qacE, or qacEΔ1 genes, whereas 13 isolates clustered (difference of ≤11 alleles by cgMLST). OXA-2 (two toilets), and OXA-2, OXA-74, PER-1 (two patients, three toilets) qacEΔ1-positive ST235 isolates dominated among VIM-2-negative isolates. The remaining seven PA strains were ST17, ST233, ST273, ST309 and ST446. Outbreak containment was achieved by replacing U-bends, and cleaning buckets, and switching from quaternary ammonium compounds (QUATs) to oxygen-releasing disinfectant products. Conclusion Comprehension and management of two simultaneous MDR PA outbreaks involving the high-risk strains ST111 and ST235 were facilitated by precise control due to identification of different outbreak sources per strain, and by the in-silico detection of high-level QUATs resistance in all isolates