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

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

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 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

Deep high-resolution X-ray spectra from cool-core clusters

We examine deep XMM-Newton Reflection Grating Spectrometer (RGS) spectra from the cores of three X-ray bright cool core galaxy clusters, Abell 262, Abell 3581 and HCG 62. Each of the RGS spectra show Fe XVII emission lines indicating the presence of gas around 0.5 keV. There is no evidence for O VII emission which would imply gas at still cooler temperatures. The range in detected gas temperature in these objects is a factor of 3.7, 5.6 and 2 for Abell 262, Abell 3581 and HCG 62, respectively. The coolest detected gas only has a volume filling fraction of 6 and 3 per cent for Abell 262 and Abell 3581, but is likely to be volume filling in HCG 62. Chandra spatially resolved spectroscopy confirms the low volume filling fractions of the cool gas in Abell 262 and Abell 3581, indicating this cool gas exists as cold blobs. Any volume heating mechanism aiming to prevent cooling would overheat the surroundings of the cool gas by a factor of 4. If the gas is radiatively cooling below 0.5 keV, it is cooling at a rate at least an order of magnitude below that at higher temperatures in Abell 262 and Abell 3581 and two-orders of magnitude lower in HCG 62. The gas may be cooling non-radiatively through mixing in these cool blobs, where the energy released by cooling is emitted in the infrared. We find very good agreement between smooth particle inference modelling of the cluster and conventional spectral fitting. Comparing the temperature distribution from this analysis with that expected in a cooling flow, there appears to be a even larger break below 0.5 keV as compared with previous empirical descriptions of the deviations of cooling flow models.Comment: 19 pages, 22 figures, accepted by MNRA

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

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

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

Evidence for Companion-Induced Secular Changes in the Turbulent Disk of a Be Star in the LMC MACHO Database

The light curve of a blue variable in the MACHO LMC database (FTS ID 78.5979.72) appeared nearly unvarying for ~4 years (quasi-flat segment) but then rapidly changed to become periodic with noisy minima for the remaining 4 years (periodic segment); there are no antecedent indications of a gradual approach to this change. Lomb Periodogram analyses indicate the presence of two distinct periods of ~61 days and 8 days in both the quasi-flat and the periodic segments. Minima of the periodic segment cover at least 50% of the orbital period and contain spikes of light with the 8-day period; maxima do not show this short period. The system typically shows maxima to be redder than minima. The most recent OGLE-III light curve shows only a 30-day periodicity. The variable's V and R magnitudes and color are those of a Be star, and recent sets of near infrared spectra four days apart, secured during the time of the OGLE-III data, show H-alpha emission near and at a maximum, confirming its Be star characteristics. The model that best fits the photometric behavior consists of a thin ring-like circumstellar disk of low mass with four obscuring sectors orbiting the central B star in unison at the 61-day period. The central star peers through the three equi- spaced separations between the four sectors producing the 8-day period. The remainder of the disk contains hydrogen in emission making maxima appear redder. A companion star of lower mass in an inclined and highly eccentric orbit produces an impulsive perturbation near its periastron to change the disk's orientation, changing eclipses from partial to complete within ~ 10 days.Comment: 42 pages, 14 figures, and 2 tables Submitted to AJ v3: Title changed, figures added, model modifie

Radial kinematics of brightest cluster galaxies

This is the first of a series of papers devoted to the investigation of a large sample of brightest cluster galaxies (BCGs), their kinematic and stellar population properties, and the relationships between those and the properties of the cluster. We have obtained high signal-to-noise ratio, long-slit spectra of these galaxies with Gemini and William Herschel Telescope with the primary purpose of investigating their stellar population properties. This paper describes the selection methods and criteria used to compile a new sample of galaxies, concentrating on BCGs previously classified as containing a halo (cD galaxies), together with the observations and data reduction. Here, we present the full sample of galaxies, and the measurement and interpretation of the radial velocity and velocity dispersion profiles of 41 BCGs. We find clear rotation curves for a number of these giant galaxies. In particular, we find rapid rotation (>100 km s−1) for two BCGs, NGC 6034 and 7768, indicating that it is unlikely that they formed through dissipationless mergers. Velocity substructure in the form of kinematically decoupled cores is detected in 12 galaxies, and we find five galaxies with velocity dispersion increasing with radius. The amount of rotation, the velocity substructure and the position of BCGs on the anisotropy–luminosity diagram are very similar to those of ‘ordinary’ giant ellipticals in high-density environments