Loss of CSMD1 expression disrupts mammary duct formation while enhancing proliferation, migration and invasion

The CUB and sushi multiple domains 1 (CSMD1) gene maps to chromosome 8p23, a region deleted in many cancers. Loss of CSMD1 expression is associated with poor prognosis in breast cancer suggesting that it acts as a tumour suppressor in this cancer. However, the function of CSMD1 is largely unknown. Herein, we investigated CSMD1 functions in cell line models. CSMD1 expression was suppressed in MCF10A and LNCaP cells using short hairpin RNA. Functional assays were performed focusing on the 'normal' MCF10A cell line. Suppression of CSMD1 significantly increased the proliferation, cell migration and invasiveness of MCF10A cells compared to shcontrols. shCSMD1 cells also showed significantly reduced adhesion to Matrigel and fibronectin. In a three-dimensional Matrigel model of MCF10A cells, reduced CSMD1 expression resulted in the development of larger and more poorly differentiated breast acini-like structures that displayed impaired lumen formation. Loss of CSMD1 expression disrupts a model of mammary duct formation while enhancing proliferation, migration and invasion. Our data suggest that CSMD1 is involved in the suppression of a transformed phenotype

Pre-main-sequence isochrones - III: The Cluster Collaboration isochrone server

We present an isochrone server for semi-empirical pre-main-sequence model isochrones in the following systems: Johnson–Cousins, Sloan Digital Sky Survey, Two-Micron All-Sky Survey, Isaac Newton Telescope (INT) Wide-Field Camera and INT Photometric Hα Survey (IPHAS)/UV-Excess Survey (UVEX). The server can be accessed via the Cluster Collaboration webpage http://www.astro.ex.ac.uk/people/timn/isochrones/. To achieve this, we have used the observed colours of member stars in young clusters with well-established age, distance and reddening to create fiducial loci in the colour–magnitude diagram. These empirical sequences have been used to quantify the discrepancy between the models and data arising from uncertainties in both the interior and atmospheric models, resulting in tables of semi-empirical bolometric corrections (BCs) in the various photometric systems. The model isochrones made available through the server are based on existing stellar interior models coupled with our newly derived semi-empirical BCs. As part of this analysis, we also present new cluster parameters for both the Pleiades and Praesepe, yielding ages of 135+20−11 and 665+14−7Myr as well as distances of 132 ± 2 and 184 ± 2 pc, respectively (statistical uncertainty only)

Pre-main-sequence isochrones - III. The cluster collaboration isochrone server

We present an isochrone server for semi-empirical pre-main-sequence model isochrones in the following systems: Johnson-Cousins, Sloan Digital Sky Survey, Two-Micron All-Sky Survey, Isaac Newton Telescope (INT) Wide-Field Camera and INT Photometric Ha Survey (IPHAS)/UV-Excess Survey (UVEX). The server can be accessed via the Cluster Collaboration webpage http://www.astro.ex.ac.uk/people/timn/isochrones/. To achieve this, we have used the observed colours ofmember stars in young clusters with well-established age, distance and reddening to create fiducial loci in the colour-magnitude diagram. These empirical sequences have been used to quantify the discrepancy between the models and data arising from uncertainties in both the interior and atmospheric models, resulting in tables of semi-empirical bolometric corrections (BCs) in the various photometric systems. The model isochrones made available through the server are based on existing stellar interior models coupled with our newly derived semi-empirical BCs. As part of this analysis, we also present new cluster parameters for both the Pleiades and Praesepe, yielding ages of 135+20 -11 and 665+14 -7 Myr as well as distances of 132 ± 2 and 184 ± 2 pc, respectively (statistical uncertainty only).JMR is funded by a UK Science and Technology Facilities Council (STFC) studentship. EEM acknowledges support from the National Science Foundation (NSF) Award AST-1008908. The authors would like to thank Emanuele Tognelli for the updated set of Pisa models and John Stauffer for sharing his catalogue of Kron photometric measurements of Pleiades members. The authors would also like to thank the referee for comments which have vastly improved the clarity of the manuscript. This research has made use of data obtained at the Isaac Newton Telescope, which is operated on the island of La Palma by the Isaac Newton Group (ING) in the Spanish Observatorio del Roque de los Muchachos of the Institutio de Astrofisica de Canarias. This research has made use of archival data products from the Two-Micron All-Sky Survey (2MASS), which is a joint project of the University of Massachusetts and the Infrared Processing and Analysis Center, funded by the National Aeronautics and Space Administration (NASA) and the National Science Foundation. This research has made use of public data from the SDSS. Funding for the SDSS was provided by the Alfred P. Sloan Foundation, the Participating Institutions, the National Science Foundation, the US Department of Energy, the National Aeronautics and Space Administration, the Japanese Monbukagakusho, the Max Planck Society and the Higher Education Funding Council for England. The SDSS was managed by the Astrophysical Research Consortium for the Participating Institutions

The characteristic blue spectra of accretion disks in quasars as uncovered in the infrared

Quasars are thought to be powered by supermassive black holes accreting surrounding gas. Central to this picture is a putative accretion disk which is believed to be the source of the majority of the radiative output. It is well known, however, that the most extensively studied disk model -- an optically thick disk which is heated locally by the dissipation of gravitational binding energy -- is apparently contradicted by observations in a few major respects. In particular, the model predicts a specific blue spectral shape asymptotically from the visible to the near-infrared, but this is not generally seen in the visible wavelength region where the disk spectrum is observable. A crucial difficulty was that, toward the infrared, the disk spectrum starts to be hidden under strong hot dust emission from much larger but hitherto unresolved scales, and thus has essentially been impossible to observe. Here we report observations of polarized light interior to the dust-emiting region that enable us to uncover this near-infrared disk spectrum in several quasars. The revealed spectra show that the near-infrared disk spectrum is indeed as blue as predicted. This indicates that, at least for the outer near-infrared-emitting radii, the standard picture of the locally heated disk is approximately correct. The model problems at shorter wavelengths should then be directed toward a better understanding of the inner parts of the revealed disk. The newly uncovered disk emission at large radii, with more future measurements, will also shed totally new light on the unanswered critical question of how and where the disk ends.Comment: published in Nature, 24 July 2008 issue. Supplementary Information can be found at http://www.mpifr-bonn.mpg.de/div/ir-interferometry/suppl_info.pdf Published version can be accessed from http://www.nature.com/nature/journal/v454/n7203/pdf/nature07114.pd

Black Hole Models of Quasars

Observations of active galactic nuclei are interpreted in terms of a theoretical model involving accretion onto a massive black hole. Optical quasars and Seyfert galaxies are associated with holes accreting near the Eddington rate and radio galaxies with sub-critical accretion. It is argued that magnetic fields are largely responsible for extracting energy and angular momentum from black holes and disks. Recent studies of electron-positron pair plasmas and their possible role in establishing the emergent X-ray spectrum are reviewed. The main evolutionary properties of active galactic nuclei can be interpreted in terms of a simple model in which black holes accrete gas at a rate dictated by the rate of gas supply which decreases with cosmic time. It may be worth searching for eclipsing binary black holes in lower power Seyferts

A systematic variation of the stellar initial mass function in early-type galaxies

Much of our knowledge of galaxies comes from analysing the radiation emitted by their stars. It depends on the stellar initial mass function (IMF) describing the distribution of stellar masses when the population formed. Consequently knowledge of the IMF is critical to virtually every aspect of galaxy evolution. More than half a century after the first IMF determination, no consensus has emerged on whether it is universal in different galaxies. Previous studies indicated that the IMF and the dark matter fraction in galaxy centres cannot be both universal, but they could not break the degeneracy between the two effects. Only recently indications were found that massive elliptical galaxies may not have the same IMF as our Milky Way. Here we report unambiguous evidence for a strong systematic variation of the IMF in early-type galaxies as a function of their stellar mass-to-light ratio, producing differences up to a factor of three in mass. This was inferred from detailed dynamical models of the two-dimensional stellar kinematics for the large Atlas3D representative sample of nearby early-type galaxies spanning two orders of magnitude in stellar mass. Our finding indicates that the IMF depends intimately on a galaxy's formation history.Comment: 4 pages, 2 figures, LaTeX. Accepted for publication as a Nature Letter. More information about our Atlas3D project is available at http://purl.org/atlas3

The Formation and Evolution of the First Massive Black Holes

The first massive astrophysical black holes likely formed at high redshifts (z>10) at the centers of low mass (~10^6 Msun) dark matter concentrations. These black holes grow by mergers and gas accretion, evolve into the population of bright quasars observed at lower redshifts, and eventually leave the supermassive black hole remnants that are ubiquitous at the centers of galaxies in the nearby universe. The astrophysical processes responsible for the formation of the earliest seed black holes are poorly understood. The purpose of this review is threefold: (1) to describe theoretical expectations for the formation and growth of the earliest black holes within the general paradigm of hierarchical cold dark matter cosmologies, (2) to summarize several relevant recent observations that have implications for the formation of the earliest black holes, and (3) to look into the future and assess the power of forthcoming observations to probe the physics of the first active galactic nuclei.Comment: 39 pages, review for "Supermassive Black Holes in the Distant Universe", Ed. A. J. Barger, Kluwer Academic Publisher

Anharmonicity, vibrational instability and Boson peak in glasses

We show that a {\em vibrational instability} of the spectrum of weakly interacting quasi-local harmonic modes creates the maximum in the inelastic scattering intensity in glasses, the Boson peak. The instability, limited by anharmonicity, causes a complete reconstruction of the vibrational density of states (DOS) below some frequency $\omega_c$, proportional to the strength of interaction. The DOS of the new {\em harmonic modes} is independent of the actual value of the anharmonicity. It is a universal function of frequency depending on a single parameter -- the Boson peak frequency, $\omega_b$ which is a function of interaction strength. The excess of the DOS over the Debye value is $\propto\omega^4$ at low frequencies and linear in $\omega$ in the interval $\omega_b \ll \omega \ll \omega_c$. Our results are in an excellent agreement with recent experimental studies.Comment: LaTeX, 8 pages, 6 figure

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente