Merging clusters of galaxies observed with XMM-Newton

We present results from the XMM-Newton observations of our ongoing program on merging clusters. To date three clusters have been observed, covering the temporal sequence from early to late stage mergers: A1750, A2065 and A3921. Using spatially-resolved spectroscopy of discrete regions, hardness ratio and temperature maps, we show that all three clusters display a complex temperature structure. In the case of A1750, a double cluster, we argue that the observed temperature structure is not only related to the ongoing merger but also to previous merger events. A2065 seems an excellent example of a `compact merger', i.e. when the centres of the two clusters have just started to interact, producing a shock in the ICM. Using comparisons with numerical simulations and complementary optical data, the highly complex temperature structure evident in A3921 is interpreted as an off-axis merger between two unequal mass components. These results illustrate the complex physics of merger events. The relaxation time can be larger than the typical time between merger events, so that the present day morphology of clusters depends not only on on-going interaction but also on the more ancient formation history.Comment: 10 pages, 3 figures. Use elsart.cls. Accepted for publication in Advances in Space Research. A version with full resolution figures can be found at http://www.star.bris.ac.uk/elena/cospar_3clusters.pd

YAP and TAZ are transcriptional co-activators of AP-1 proteins and STAT3 during breast cellular transformation

The YAP and TAZ paralogs are transcriptional co-activators recruited to target sites by TEAD proteins. Here, we show that YAP and TAZ are also recruited by JUNB (a member of the AP-1 family) and STAT3, key transcription factors that mediate an epigenetic switch linking inflammation to cellular transformation. YAP and TAZ directly interact with JUNB and STAT3 via a WW domain important for transformation, and they stimulate transcriptional activation by AP-1 proteins. JUNB, STAT3, and TEAD co-localize at virtually all YAP/TAZ target sites, yet many target sites only contain individual AP-1, TEAD, or STAT3 motifs. This observation and differences in relative crosslinking efficiencies of JUNB, TEAD, and STAT3 at YAP/TAZ target sites suggest that YAP/TAZ is recruited by different forms of an AP-1/STAT3/TEAD complex depending on the recruiting motif. The different classes of YAP/TAZ target sites are associated with largely non-overlapping genes with distinct functions. A small minority of target sites are YAP- or TAZ-specific, and they are associated with different sequence motifs and gene classes from shared YAP/TAZ target sites. Genes containing either the AP-1 or TEAD class of YAP/TAZ sites are associated with poor survival of breast cancer patients with the triple-negative form of the disease

YAP and TAZ are transcriptional co-activators of AP-1 proteins and STAT3 during breast cellular transformation [preprint]

The YAP and TAZ paralogues are transcriptional co-activators recruited to target sites, primarily by TEAD proteins. Here, we show that YAP and TAZ are also recruited by JUNB and STAT3, key factors that mediate an epigenetic switch linking inflammation to cellular transformation. YAP and TAZ directly interact with JUNB and STAT3 via a WW domain important for transformation, co-occupy many target sites in vivo via AP-1 and (to a lesser extent) STAT3 sequence motifs, and stimulate transcriptional activation by AP-1 proteins. A few target sites are YAP- or TAZ-specific, and they are associated with different sequence motifs and gene classes. YAP/TAZ, JUNB, and STAT3 directly regulate a common set of target genes that overlap, but are distinct from, those regulated by YAP/TAZ and TEADs. The set of genes regulated by YAP/TAZ, STAT3, and JUNB is associated with poor survival in breast cancer patients with the triple-negative form of the disease

Factorbook: an Updated Catalog of Transcription Factor Motifs and Candidate Regulatory Motif Sites [preprint]

The human genome contains roughly 1,600 transcription factors (TFs) (1), DNA-binding proteins recognizing characteristic sequence motifs to exert regulatory effects on gene expression. The binding specificities of these factors have been profiled both in vitro, using techniques such as HT-SELEX (2), and in vivo, using techniques including ChIP-seq (3, 4). We previously developed Factorbook, a TF-centric database of annotations, motifs, and integrative analyses based on ChIP-seq data from Phase II of the ENCODE Project. Here we present an update to Factorbook which significantly expands the breadth of cell type and TF coverage. The update includes an expanded motif catalog derived from thousands of ENCODE Phase II and III ChIP-seq experiments and HT-SELEX experiments; this motif catalog is integrated with the ENCODE registry of candidate cis-regulatory elements to annotate a comprehensive collection of genome-wide candidate TF binding sites. The database also offers novel tools for applying the motif models within machine learning frameworks and using these models for integrative analysis, including annotation of variants and disease and trait heritability. We will continue to expand the resource as ENCODE Phase IV data are released

Self Consistent Molecular Field Theory for Packing in Classical Liquids

Building on a quasi-chemical formulation of solution theory, this paper proposes a self consistent molecular field theory for packing problems in classical liquids, and tests the theoretical predictions for the excess chemical potential of the hard sphere fluid. Results are given for the self consistent molecular fields obtained, and for the probabilities of occupancy of a molecular observation volume. For this system, the excess chemical potential predicted is as accurate as the most accurate prior theories, particularly the scaled particle (Percus-Yevick compressibility) theory. It is argued that the present approach is particularly simple, and should provide a basis for a molecular-scale description of more complex solutions.Comment: 6 pages and 5 figure

Differential analysis of chromatin accessibility and histone modifications for predicting mouse developmental enhancers

Enhancers are distal cis-regulatory elements that modulate gene expression. They are depleted of nucleosomes and enriched in specific histone modifications; thus, calling DNase-seq and histone mark ChIP-seq peaks can predict enhancers. We evaluated nine peak-calling algorithms for predicting enhancers validated by transgenic mouse assays. DNase and H3K27ac peaks were consistently more predictive than H3K4me1/2/3 and H3K9ac peaks. DFilter and Hotspot2 were the best DNase peak callers, while HOMER, MUSIC, MACS2, DFilter and F-seq were the best H3K27ac peak callers. We observed that the differential DNase or H3K27ac signals between two distant tissues increased the area under the precision-recall curve (PR-AUC) of DNase peaks by 17.5-166.7% and that of H3K27ac peaks by 7.1-22.2%. We further improved this differential signal method using multiple contrast tissues. Evaluated using a blind test, the differential H3K27ac signal method substantially improved PR-AUC from 0.48 to 0.75 for predicting heart enhancers. We further validated our approach using postnatal retina and cerebral cortex enhancers identified by massively parallel reporter assays, and observed improvements for both tissues. In summary, we compared nine peak callers and devised a superior method for predicting tissue-specific mouse developmental enhancers by reranking the called peaks

The large-scale shock in the cluster of galaxies Hydra A

We analyzed a deep XMM-Newton observation of the cluster of galaxies Hydra A, focusing on the large-scale shock discovered as a surface brightness discontinuity in Chandra images. The shock front can be seen both in the pressure map and in temperature profiles in several sectors. The Mach numbers determined from the temperature jumps are in good agreement with the Mach numbers derived from EPIC/pn surface brightness profiles and previously from Chandra data and are consistent with M~1.3. The estimated shock age in the different sectors using a spherically symmetric point explosion model ranges between 130 and 230 Myr and the outburst energy between 1.5 and 3e61 ergs. The shape of the shock seen in the pressure map can be approximated with an ellipse centered 70 kpc towards the NE from the cluster center. We aimed to develop a better model that can explain the offset between the shock center and the AGN and give a consistent result on the shock age and energy. To this end, we performed 3D hydrodynamical simulations in which the shock is produced by a symmetrical pair of AGN jets launched in a spherical galaxy cluster. As an explanation of the observed offset of the shock center, we consider large-scale bulk flows in the intracluster medium. The simulation successfully reproduces the size, ellipticity, and average Mach number of the observed shock front. The predicted age of the shock is 160 Myr and the total input energy 3e61 erg. Both values are within the range determined by the spherically symmetric model. Matching the observed 70 kpc offset of the shock ellipse from the cluster center requires large-scale coherent motions with a high velocity of 670 km/s. We discuss the feasibility of this scenario and offer alternative ways to produce the offset and to further improve the simulation.Comment: 14 pages, accepted for publication in A&A, minor revision compared to previous versio

HIFLUGCS: Galaxy cluster scaling relations between X-ray luminosity, gas mass, cluster radius, and velocity dispersion

We present relations between X-ray luminosity and velocity dispersion (L-sigma), X-ray luminosity and gas mass (L-Mgas), and cluster radius and velocity dispersion (r500-sigma) for 62 galaxy clusters in the HIFLUGCS, an X-ray flux-limited sample minimizing bias toward any cluster morphology. Our analysis in total is based on ~1.3Ms of clean X-ray XMM-Newton data and 13439 cluster member galaxies with redshifts. Cool cores are among the major contributors to the scatter in the L-sigma relation. When the cool-core-corrected X-ray luminosity is used the intrinsic scatter decreases to 0.27 dex. Even after the X-ray luminosity is corrected for the cool core, the scatter caused by the presence of cool cores dominates for the low-mass systems. The scatter caused by the non-cool-core clusters does not strongly depend on the mass range, and becomes dominant in the high-mass regime. The observed L-sigma relation agrees with the self-similar prediction, matches that of a simulated sample with AGN feedback disregarding six clusters with <45 cluster members with spectroscopic redshifts, and shows a common trend of increasing scatter toward the low-mass end, i.e., systems with sigma<500km/s. A comparison of observations with simulations indicates an AGN-feedback-driven impact in the low-mass regime. The best fits to the $L-M_{\rm gas}$ relations for the disturbed clusters and undisturbed clusters in the observational sample closely match those of the simulated samples with and without AGN feedback, respectively. This suggests that one main cause of the scatter is AGN activity providing feedback in different phases, e.g., during a feedback cycle. The slope and scatter in the observed r500-sigma relation is similar to that of the simulated sample with AGN feedback except for a small offset but still within the scatter.Comment: 45 pages, 28 figures, A&A proof-version, high-resolution figures in Appendix F can be found in the electronic version on the A&A we

A Comparative Study of Local Galaxy Clusters: I. Derived X-ray Observables

We examine systematic differences in the derived X-ray properties of galaxy clusters as reported by three different groups: Vikhlinin et al. (2009a), Mantz et al. (2010b), and Planck Collaboration (2011b). The sample overlap between any two pairs of works ranges between 16 to 28 galaxy clusters in common. We find systematic differences in most reported properties, including the total cluster mass, M500. The most extreme case is an average 45% \pm 5% difference in cluster mass between the Planck Collaboration (2011b) and Mantz et al. (2010b), for clusters at z > 0.13 (averaged over 16 clusters). These mass differences induce differences in cluster observables defined within an R500 aperture. After accounting for aperture differences, we find very good agreement in gas mass estimates between the different groups. However, the soft-band X-ray luminosity, LX, core-excised spectroscopic temperature, TX, and gas thermal energy, YX = MgasTX display mean differences at the 5%-15% level. We also find that the low (z \leq 0.13) and high (z \geq 0.13) galaxy cluster samples in Planck Collaboration (2011b) appear to be systematically different: the YSZ/YX ratio for these two sub- samples is ln(YSZ/YX) = -0.06 \pm 0.04 and ln(YSZ/YX) = 0.08 \pm 0.04 for the low and high redshift sub-samples respectively.Comment: feedback welcom

Generating real-world evidence on the quality use, benefits and safety of medicines in australia: History, challenges and a roadmap for the future

Australia spends more than $20 billion annually on medicines, delivering significant health benefits for the population. However, inappropriate prescribing and medicine use also result in harm to individuals and populations, and waste of precious health resources. Medication data linked with other routine collections enable evidence generation in pharmacoepidemiology; the science of quantifying the use, effectiveness and safety of medicines in real-world clinical practice. This review details the history of medicines policy and data access in Australia, the strengths of existing data sources, and the infrastructure and governance enabling and impeding evidence generation in the field. Currently, substantial gaps persist with respect to cohesive, contemporary linked data sources supporting quality use of medicines, effectiveness and safety research; exemplified by Aus-tralia’s limited capacity to contribute to the global effort in real-world studies of vaccine and dis-ease-modifying treatments for COVID-19. We propose a roadmap to bolster the discipline, and population health more broadly, underpinned by a distinct capability governing and streamlining access to linked data assets for accredited researchers. Robust real-world evidence generation requires current data roadblocks to be remedied as a matter of urgency to deliver efficient and equitable health care and improve the health and well-being of all Australians