The Antitumorigenic Function of EGFR in Metastatic Breast Cancer is Regulated by Expression of Mig6

Numerous studies by our lab and others demonstrate that epidermal growth factor receptor (EGFR) plays critical roles in primary breast cancer (BC) initiation, growth and dissemination. However, clinical trials targeting EGFR function in BC have lead to disappointing results. In the current study we sought to identify the mechanisms responsible for this disparity by investigating the function of EGFR across the continuum of the metastatic cascade. We previously established that overexpression of EGFR is sufficient for formation of in situ primary tumors by otherwise nontransformed murine mammary gland cells. Induction of epithelial-mesenchymal transition (EMT) is sufficient to drive the metastasis of these EGFR-transformed tumors. Examining growth factor receptor expression across this and other models revealed a potent downregulation of EGFR through metastatic progression. Consistent with diminution of EGFR following EMT and metastasis EGF stimulation changes from a proliferative to an apoptotic response in in situ versus metastatic tumor cells, respectively. Furthermore, overexpression of EGFR in metastatic MDA-MB-231 BC cells promoted their antitumorigenic response to EGF in three dimensional (3D) metastatic outgrowth assays. In line with the paradoxical function of EGFR through EMT and metastasis we demonstrate that the EGFR inhibitory molecule, Mitogen Induced Gene-6 (Mig6), is tumor suppressive in in situ tumor cells. However, Mig6 expression is absolutely required for prevention of apoptosis and ultimate metastasis of MDA-MB-231 cells. Further understanding of the paradoxical function of EGFR between primary and metastatic tumors will be essential for application of its targeted molecular therapies in BC

Optical research: a curated visual music collection

Optical Research is a curated collection of visual music by a group of 12 international artists, which has recently been presented as a DVD, a gallery installation, and will be presented at the British Computer Society Electronic Visualisation and the Arts: EVA London 2015

The giant lobes of Centaurus A observed at 118 MHz with the Murchison Widefield Array

We present new wide-field observations of Centaurus A (Cen A) and the surrounding region at 118MHz with the Murchison Widefield Array (MWA) 32-tile prototype, with which we investigate the spectral-index distribution of Cen A's giant radio lobes.We compa

A multi-wavelength study of the young star V1118 Orionis in outburst

Abriged version for astroph: The young late-type star V1118 Orionis was in outburst from 2005 to 2006. We followed the outburst with optical and near-infrared photometry; the X-ray emission was further probed with observations taken with XMM-Newton and Chandra during and after the outburst. In addition, we obtained mid-infrared photometry and spectroscopy with Spitzer at the peak of the outburst and in the post-outburst phase. The spectral energy distribution of V1118 Ori varied significantly over the course of the outburst. The optical flux showed the largest variations, most likely due to enhanced emission by a hot spot. The latter dominated the optical and near-infrared emission at the peak of the outburst, while the disk emission dominated in the mid-infrared. The X-ray flux correlated with the optical and infrared fluxes, indicating that accretion affected the magnetically active corona and the stellar magnetosphere. The thermal structure of the corona was variable with some indication of a cooling of the coronal temperature in the early phase of the outburst with a gradual return to normal values. Color-color diagrams in the optical and infrared showed variations during the outburst, with no obvious signature of reddening due to circumstellar matter. Using MC realizations of star+disk+hotspot models to fit the SED in ``quiescence'' and at the peak of the outburst, we determined that the mass accretion rate varied from about 2.5E-7 Msun/yr to 1E-6 Msun/yr; in addition the fractional area of the hotspot increased significantly as well. The multi-wavelength study of the V1118 Ori outburst helped us to understand the variations in spectral energy distributions and demonstrated the interplay between the disk and the stellar magnetosphere in a young, strongly accreting star.Comment: Accepted in A&A, Tables will be published onlin

Resolved 24.5 micron emission from massive young stellar objects

Massive young stellar objects (MYSO) are surrounded by massive dusty envelopes. Our aim is to establish their density structure on scales of ~1000 AU, i.e. a factor 10 increase in angular resolution compared to similar studies performed in the (sub)mm. We have obtained diffraction-limited (0.6") 24.5 micron images of 14 well-known massive star formation regions with Subaru/COMICS. The images reveal the presence of discrete MYSO sources which are resolved on arcsecond scales. For many sources, radiative transfer models are capable of satisfactorily reproducing the observations. They are described by density powerlaw distributions (n(r) ~ r^(-p)) with p = 1.0 +/-0.25. Such distributions are shallower than those found on larger scales probed with single-dish (sub)mm studies. Other sources have density laws that are shallower/steeper than p = 1.0 and there is evidence that these MYSOs are viewed near edge-on or near face-on, respectively. The images also reveal a diffuse component tracing somewhat larger scale structures, particularly visible in the regions S140, AFGL 2136, IRAS 20126+4104, Mon R2, and Cep A. We thus find a flattening of the MYSO envelope density law going from ~10 000 AU down to scales of ~1000 AU. We propose that this may be evidence of rotational support of the envelope (abridged).Comment: 21 pages, accepted for A&

The Holst Spin Foam Model via Cubulations

Spin foam models are an attempt for a covariant, or path integral formulation of canonical loop quantum gravity. The construction of such models usually rely on the Plebanski formulation of general relativity as a constrained BF theory and is based on the discretization of the action on a simplicial triangulation, which may be viewed as an ultraviolet regulator. The triangulation dependence can be removed by means of group field theory techniques, which allows one to sum over all triangulations. The main tasks for these models are the correct quantum implementation of the Plebanski constraints, the existence of a semiclassical sector implementing additional "Regge-like" constraints arising from simplicial triangulations, and the definition of the physical inner product of loop quantum gravity via group field theory. Here we propose a new approach to tackle these issues stemming directly from the Holst action for general relativity, which is also a proper starting point for canonical loop quantum gravity. The discretization is performed by means of a "cubulation" of the manifold rather than a triangulation. We give a direct interpretation of the resulting spin foam model as a generating functional for the n-point functions on the physical Hilbert space at finite regulator. This paper focuses on ideas and tasks to be performed before the model can be taken seriously. However, our analysis reveals some interesting features of this model: first, the structure of its amplitudes differs from the standard spin foam models. Second, the tetrad n-point functions admit a "Wick-like" structure. Third, the restriction to simple representations does not automatically occur -- unless one makes use of the time gauge, just as in the classical theory.Comment: 25 pages, 1 figure; v3: published version. arXiv admin note: substantial text overlap with arXiv:0911.213

Spitzer SAGE Infrared Photometry of Massive Stars in the Large Magellanic Cloud

We present a catalog of 1750 massive stars in the Large Magellanic Cloud, with accurate spectral types compiled from the literature, and a photometric catalog for a subset of 1268 of these stars, with the goal of exploring their infrared properties. The photometric catalog consists of stars with infrared counterparts in the Spitzer SAGE survey database, for which we present uniform photometry from 0.3-24 microns in the UBVIJHKs+IRAC+MIPS24 bands. The resulting infrared color-magnitude diagrams illustrate that the supergiant B[e], red supergiant and luminous blue variable (LBV) stars are among the brightest infrared point sources in the Large Magellanic Cloud, due to their intrinsic brightness, and at longer wavelengths, due to dust. We detect infrared excesses due to free-free emission among ~900 OB stars, which correlate with luminosity class. We confirm the presence of dust around 10 supergiant B[e] stars, finding the shape of their spectral energy distributions (SEDs) to be very similar, in contrast to the variety of SED shapes among the spectrally variable LBVs. The similar luminosities of B[e] supergiants (log L/Lo>=4) and the rare, dusty progenitors of the new class of optical transients (e.g. SN 2008S and NGC 300 OT), plus the fact that dust is present in both types of objects, suggests a common origin for them. We find the infrared colors for Wolf-Rayet stars to be independent of spectral type and their SEDs to be flatter than what models predict. The results of this study provide the first comprehensive roadmap for interpreting luminous, massive, resolved stellar populations in nearby galaxies at infrared wavelengths.Comment: 57 pages, 19 figures, 5 tables, accepted for publication in the Astronomical Journal (v3 corrects typos

The Murchison Widefield Array: Design Overview

The Murchison Widefield Array (MWA) is a dipole-based aperture array synthesis telescope designed to operate in the 80-300 MHz frequency range. It is capable of a wide range of science investigations, but is initially focused on three key science projects. These are detection and characterization of 3-dimensional brightness temperature fluctuations in the 21cm line of neutral hydrogen during the Epoch of Reionization (EoR) at redshifts from 6 to 10, solar imaging and remote sensing of the inner heliosphere via propagation effects on signals from distant background sources,and high-sensitivity exploration of the variable radio sky. The array design features 8192 dual-polarization broad-band active dipoles, arranged into 512 tiles comprising 16 dipoles each. The tiles are quasi-randomly distributed over an aperture 1.5km in diameter, with a small number of outliers extending to 3km. All tile-tile baselines are correlated in custom FPGA-based hardware, yielding a Nyquist-sampled instantaneous monochromatic uv coverage and unprecedented point spread function (PSF) quality. The correlated data are calibrated in real time using novel position-dependent self-calibration algorithms. The array is located in the Murchison region of outback Western Australia. This region is characterized by extremely low population density and a superbly radio-quiet environment,allowing full exploitation of the instrumental capabilities.Comment: 9 pages, 5 figures, 1 table. Accepted for publication in Proceedings of the IEE

Ice chemistry in embedded young stellar objects in the Large Magellanic Cloud

We present spectroscopic observations of a sample of 15 embedded young stellar objects (YSOs) in the Large Magellanic Cloud (LMC). These observations were obtained with the Spitzer Infrared Spectrograph (IRS) as part of the SAGE-Spec Legacy program. We analyze the two prominent ice bands in the IRS spectral range: the bending mode of CO_2 ice at 15.2 micron and the ice band between 5 and 7 micron that includes contributions from the bending mode of water ice at 6 micron amongst other ice species. The 5-7 micron band is difficult to identify in our LMC sample due to the conspicuous presence of PAH emission superimposed onto the ice spectra. We identify water ice in the spectra of two sources; the spectrum of one of those sources also exhibits the 6.8 micron ice feature attributed to ammonium and methanol. We model the CO_2 band in detail, using the combination of laboratory ice profiles available in the literature. We find that a significant fraction (> 50%) of CO_2 ice is locked in a water-rich component, consistent with what is observed for Galactic sources. The majority of the sources in the LMC also require a pure-CO_2 contribution to the ice profile, evidence of thermal processing. There is a suggestion that CO_2 production might be enhanced in the LMC, but the size of the available sample precludes firmer conclusions. We place our results in the context of the star formation environment in the LMC.Comment: Minor corrections to Table 2. Accepted for publication in ApJ, 66 pages, 9 figures (some in color), 4 table