Human gene copy number spectra analysis in congenital heart malformations

The clinical significance of copy number variants (CNVs) in congenital heart disease (CHD) continues to be a challenge. Although CNVs including genes can confer disease risk, relationships between gene dosage and phenotype are still being defined. Our goal was to perform a quantitative analysis of CNVs involving 100 well-defined CHD risk genes identified through previously published human association studies in subjects with anatomically defined cardiac malformations. A novel analytical approach permitting CNV gene frequency “spectra” to be computed over prespecified regions to determine phenotype-gene dosage relationships was employed. CNVs in subjects with CHD (n = 945), subphenotyped into 40 groups and verified in accordance with the European Paediatric Cardiac Code, were compared with two control groups, a disease-free cohort (n = 2,026) and a population with coronary artery disease (n = 880). Gains (≥200 kb) and losses (≥100 kb) were determined over 100 CHD risk genes and compared using a Barnard exact test. Six subphenotypes showed significant enrichment (P ≤ 0.05), including aortic stenosis (valvar), atrioventricular canal (partial), atrioventricular septal defect with tetralogy of Fallot, subaortic stenosis, tetralogy of Fallot, and truncus arteriosus. Furthermore, CNV gene frequency spectra were enriched (P ≤ 0.05) for losses at: FKBP6, ELN, GTF2IRD1, GATA4, CRKL, TBX1, ATRX, GPC3, BCOR, ZIC3, FLNA and MID1; and gains at: PRKAB2, FMO5, CHD1L, BCL9, ACP6, GJA5, HRAS, GATA6 and RUNX1. Of CHD subjects, 14% had causal chromosomal abnormalities, and 4.3% had likely causal (significantly enriched), large, rare CNVs. CNV frequency spectra combined with precision phenotyping may lead to increased molecular understanding of etiologic pathways

The architecture of Abell 1386 and its relationship to the Sloan Great Wall

We present new radial velocities from AAOmega on the Anglo-Australian Telescope for 307 galaxies (b_J < 19.5) in the region of the rich cluster Abell 1386. Consistent with other studies of galaxy clusters that constitute sub-units of superstructures, we find that the velocity distribution of A1386 is very broad (21,000--42,000 kms^-1, or z=0.08--0.14) and complex. The mean redshift of the cluster that Abell designated as number 1386 is found to be ~0.104. However, we find that it consists of various superpositions of line-of-sight components. We investigate the reality of each component by testing for substructure and searching for giant elliptical galaxies in each and show that A1386 is made up of at least four significant clusters or groups along the line of sight whose global parameters we detail. Peculiar velocities of brightest galaxies for each of the groups are computed and found to be different from previous works, largely due to the complexity of the sky area and the depth of analysis performed in the present work. We also analyse A1386 in the context of its parent superclusters: Leo A, and especially the Sloan Great Wall. Although the new clusters may be moving toward mass concentrations in the Sloan Great Wall or beyond, many are most likely not yet physically bound to it.Comment: 21 pages, 9 figures, includes the full appendix table. Accepted for publication in MNRA

Suzaku measurement of Abell 2204's intracluster gas temperature profile out to 1800 kpc

Context: Measurements of intracluster gas temperatures out to large radii are important for the use of clusters for precision cosmology and for studies of cluster physics. Previous attempts to measure robust temperatures at cluster virial radii failed. Aims: The goal of this work is to measure the temperature profile of the very relaxed galaxy cluster Abell 2204 out to large radii, possibly reaching the virial radius. Methods: Taking advantage of its low particle background due to its low-Earth orbit, Suzaku data are used to measure the outer temperature profile of Abell 2204. These data are combined with Chandra and XMM-Newton data of the same cluster in order to make the connection to the inner regions, unresolved by Suzaku, and to determine the smearing due to Suzaku's PSF. Results: The temperature profile of Abell 2204 is determined from 10 kpc to 1800 kpc, close to an estimate of r200 (the approximation to the virial radius). The temperature rises steeply from below 4 keV in the very center up to more than 8 keV in the intermediate range and then decreases again to about 4 keV at the largest radii. Varying the measured particle background normalization artificially by +-10 percent does not change the results significantly. Predictions for outer temperature profiles based on hydrodynamic simulations show good agreement. In particular, we find the observed temperature profile to be slightly steeper but consistent with a drop of a factor of 0.6 from 0.3 r200 to r200, as predicted by simulations. Conclusions: Temperature measurements up to the virial radius seem feasible with Suzaku, when a careful analysis of the different background components and the effects of the PSF is performed. The result obtained here indicates that numerical simulations capture the intracluster gas physics well in cluster outskirts.Comment: 7 pages; Astronomy and Astrophysics, accepted; additional systematic effects have been quantified, results unchanged; also available at http://www.reiprich.ne

The Northern ROSAT All-Sky (NORAS) Galaxy Cluster Survey I: X-ray Properties of Clusters Detected as Extended X-ray Sources

In the construction of an X-ray selected sample of galaxy clusters for cosmological studies, we have assembled a sample of 495 X-ray sources found to show extended X-ray emission in the first processing of the ROSAT All-Sky Survey. The sample covers the celestial region with declination $\delta \ge 0\deg$ and galactic latitude $|b_{II}| \ge 20\deg$ and comprises sources with a count rate $\ge 0.06$ counts s$^{-1}$ and a source extent likelihood of 7. In an optical follow-up identification program we find 378 (76%) of these sources to be clusters of galaxies. ...Comment: 61 pages; ApJS in press; fixed bug in table file; also available at (better image quality) http://www.xray.mpe.mpg.de/theorie/NORAS

The XMM–NEWTON Ω Project: I. The X-ray luminosity – temperature relation at z>0.4

We describe XMM-Newton Guaranteed Time observations of a sample of eight high redshift (0.45 < z < rvirial) bolometric luminosities, performed β-model fits to the radial surface profiles and made spectral fits to a single temperature isothermal model. We describe data analysis techniques that pay particular attention to background mitigation. We have also estimated temperatures and luminosities for two known clusters (Abell 2246 and RXJ1325.0-3814), and one new high redshift cluste r candidate (XMMU J084701.8 +345117), that were detected o ff-axis. Characterizing the L x − Tx relation as L x = L 6 ( T 6keV ) α , we find L 6 = 15 . 9 + 7 . 6 − 5 . 2 × 1044erg s − 1 and α =2.7 ±0.4 for an Ω Λ = 0 . 0 , Ω M = 1 .0, H0 = 50 km s − 1 Mpc − 1 cosmology at a typical redshift z ∼ 0 .55. Comparing with the low redshift study by Markevitch, 1998, we find α to be in agreement, and assuming L x − Tx to evolve as (1 + z ) A , we find A =0.68 ±0.26 for the same cosmology and A = 1 .52 + 0 .26 − 0 .27 for an Ω Λ = 0 . 7 , Ω M = 0 . 3 cosmology. Our A values are very similar to those found previously by Vikhlinin et al., 2002 using a compilation of Chandra observations of 0 .39 < z < 1 .26 clusters. We conclude that there is now evidence from both XMM-Newton and Chandra for an evolutionary trend in the L x − Tx relation. This evolution is significantly below the level expected from the predictions of the self-similar model for an Ω Λ = 0 . 0 , Ω M = 1 .0, cosmology, but consistent with self-similar model in an Ω Λ = 0 . 7 , Ω M = 0 . 3 cosmology. Our observations lend support to the robustness and completeness of the SHARC and 160SD surveys

Mark correlations: relating physical properties to spatial distributions

Mark correlations provide a systematic approach to look at objects both distributed in space and bearing intrinsic information, for instance on physical properties. The interplay of the objects' properties (marks) with the spatial clustering is of vivid interest for many applications; are, e.g., galaxies with high luminosities more strongly clustered than dim ones? Do neighbored pores in a sandstone have similar sizes? How does the shape of impact craters on a planet depend on the geological surface properties? In this article, we give an introduction into the appropriate mathematical framework to deal with such questions, i.e. the theory of marked point processes. After having clarified the notion of segregation effects, we define universal test quantities applicable to realizations of a marked point processes. We show their power using concrete data sets in analyzing the luminosity-dependence of the galaxy clustering, the alignment of dark matter halos in gravitational $N$-body simulations, the morphology- and diameter-dependence of the Martian crater distribution and the size correlations of pores in sandstone. In order to understand our data in more detail, we discuss the Boolean depletion model, the random field model and the Cox random field model. The first model describes depletion effects in the distribution of Martian craters and pores in sandstone, whereas the last one accounts at least qualitatively for the observed luminosity-dependence of the galaxy clustering.Comment: 35 pages, 12 figures. to be published in Lecture Notes of Physics, second Wuppertal conference "Spatial statistics and statistical physics

Redshifts, Sample Purity, and BCG Positions for the Galaxy Cluster Catalog from the First 720 Square Degrees of the South Pole Telescope Survey

We present the results of the ground- and space-based optical and near-infrared (NIR) follow-up of 224 galaxy cluster candidates detected with the Sunyaev-Zel'dovich (SZ) effect in the 720 deg^2 of the South Pole Telescope (SPT) survey completed in the 2008 and 2009 observing seasons. We use the optical/NIR data to establish whether each candidate is associated with an overdensity of galaxies and to estimate the cluster redshift. Most photometric redshifts are derived through a combination of three different cluster redshift estimators using red-sequence galaxies, resulting in an accuracy of Δz/(1 + z) = 0.017, determined through comparison with a subsample of 57 clusters for which we have spectroscopic redshifts. We successfully measure redshifts for 158 systems and present redshift lower limits for the remaining candidates. The redshift distribution of the confirmed clusters extends to z = 1.35 with a median of z_(med) = 0.57. Approximately 18% of the sample with measured redshifts lies at z > 0.8. We estimate a lower limit to the purity of this SPT SZ-selected sample by assuming that all unconfirmed clusters are noise fluctuations in the SPT data. We show that the cumulative purity at detection significance ξ > 5(ξ > 4.5) is ≥95% (≥70%). We present the red brightest cluster galaxy (rBCG) positions for the sample and examine the offsets between the SPT candidate position and the rBCG. The radial distribution of offsets is similar to that seen in X-ray-selected cluster samples, providing no evidence that SZ-selected cluster samples include a different fraction of recent mergers from X-ray-selected cluster samples

Planck 2015 results. XXVII. The second Planck catalogue of Sunyaev-Zeldovich sources

We present the all-sky Planck catalogue of Sunyaev-Zeldovich (SZ) sources detected from the 29 month full-mission data. The catalogue (PSZ2) is the largest SZ-selected sample of galaxy clusters yet produced and the deepest systematic all-sky surveyof galaxy clusters. It contains 1653 detections, of which 1203 are confirmed clusters with identified counterparts in external data sets, and is the first SZ-selected cluster survey containing >103 confirmed clusters. We present a detailed analysis of the survey selection function in terms of its completeness and statistical reliability, placing a lower limit of 83% on the purity. Using simulations, we find that the estimates of the SZ strength parameter Y5R500are robust to pressure-profile variation and beam systematics, but accurate conversion to Y500 requires the use of prior information on the cluster extent. We describe the multi-wavelength search for counterparts in ancillary data, which makes use of radio, microwave, infra-red, optical, and X-ray data sets, and which places emphasis on the robustness of the counterpart match. We discuss the physical properties of the new sample and identify a population of low-redshift X-ray under-luminous clusters revealed by SZ selection. These objects appear in optical and SZ surveys with consistent properties for their mass, but are almost absent from ROSAT X-ray selected samples

Direct optimization across computer generated reaction networks balances materials use and feasibility of synthesis plans for molecule libraries

The synthesis of thousands of candidate compounds in drug discovery and development offers opportunities for computer-aided synthesis planning to simplify the synthesis of molecule libraries by leveraging common starting materials and reaction conditions. We develop an optimization-based method to analyze large organic chemical reaction networks and design overlapping synthesis plans for entire molecule libraries so as to minimize the overall number of unique chemical compounds needed as either starting materials or reaction conditions. We consider multiple objectives, including the number of starting materials, the number of catalysts/solvents/reagents, and the likelihood of success of the overall syntheses plan, to select an optimal reaction network to access the target molecules. The library synthesis planning task was formulated as a network flow optimization problem, and we design an efficient decomposition scheme that reduces solution time by a factor of 5 and scales to instance with 48 target molecules and nearly 8000 intermediate reactions within hours. In four case studies of pharmaceutical compounds, the approach reduces the number of starting materials and catalysts/solvents/reagents needed by 32.2 and 66.0% on average and up to 63.2 and 80.0% in the best cases. The code implementation can be found at [https://github.com/Coughy1991/Molecule_library_synthesis](https://github.com/Coughy1991/Molecule_library_synthesis) Supporting information: [https://pubs.acs.org/doi/10.1021/acs.jcim.0c01032?goto=supporting-info](https://pubs.acs.org/doi/10.1021/acs.jcim.0c01032?goto=supporting-info

Cosmological parameters from the clustering of AGN

We attempt to put constraints on different cosmological and biasing models by combining the recent clustering results of X-ray sources in the local ($z\le 0.1$) and distant universe ($z\sim 1$).Comment: 9 pages, 3 figures, to be published in the proceedings of the ''2nd Hellenic Cosmology Workshop'', Athens 2001, eds, Manolis Plionis & Spiros Kotsaki