The H-band Emitting Region of the Luminous Blue Variable P Cygni: Spectrophotometry and Interferometry of the Wind

This is the final version of the article. Available from American Astronomical Society / IOP Publishing via the DOI in this record.We present the first high angular resolution observations in the near-infrared H band (1.6 μm) of the luminous blue variable star P Cygni. We obtained six-telescope interferometric observations with the CHARA Array and the MIRC beam combiner. These show that the spatial flux distribution is larger than expected for the stellar photosphere. A two-component model for the star (uniform disk) plus a halo (two-dimensional Gaussian) yields an excellent fit of the observations, and we suggest that the halo corresponds to flux emitted from the base of the stellar wind. This wind component contributes about 45% of the H-band flux and has an angular FWHM = 0.96 mas, compared to the predicted stellar diameter of 0.41 mas. We show several images reconstructed from the interferometric visibilities and closure phases, and they indicate a generally spherical geometry for the wind. We also obtained near-infrared spectrophotometry of P Cygni from which we derive the flux excess compared to a purely photospheric spectral energy distribution. The H-band flux excess matches that from the wind flux fraction derived from the two-component fits to the interferometry. We find evidence of significant near-infrared flux variability over the period from 2006 to 2010 that appears similar to the variations in the Hα emission flux from the wind.We acknowledge with thanks the variable star observations from the AAVSO International Database contributed by observers worldwide and used in this research. Support for Ritter Astrophysical Research Center during the time of the observations was provided by the National Science Foundation Program for Research and Education with Small Telescopes (NSF-PREST) under grant AST-0440784 (N.D.M.). This work was also supported by the National Science Foundation under grants AST-0606861 and AST-1009080 (D.R.G.). N.D.R. gratefully acknowledges his current CRAQ postdoctoral fellowship. We are grateful for the insightful comments of A. F. J. Moffat that improved portions of the paper, discussions with Paco Najarro and Luc Dessart about spectroscopic modeling of P Cygni, and support of the MIRC 6 telescope beam combiner by Ettore Pedretti. Institutional support has been provided by the GSU College of Arts and Sciences and by the Research Program Enhancement fund of the Board of Regents of the University System of Georgia, administered through the GSU Office of the Vice President for Research. Operational funding for the CHARA Array is provided by the GSU College of Arts and Sciences, by the National Science Foundation through grants AST-0606958 and AST-0908253, by the W. M. Keck Foundation, and by the NASA Exoplanet Science Institute. We thank the Mount Wilson Institute for providing infrastructure support at Mount Wilson Observatory. The CHARA Array, operated by Georgia State University, was built with funding provided by the National Science Foundation, Georgia State University, the W. M. Keck Foundation, and the David and Lucile Packard Foundation. This research was conducted in part using the Mimir instrument, jointly developed at Boston University and Lowell Observatory and supported by NASA, NSF, and the W. M. Keck Foundation. J.D.M. acknowledges University of Michigan and NSF AST-0707927 for support of MIRC construction and observations. D.P.C. acknowledges support under NSF AST-0907790 to Boston University. We gratefully acknowledge all of this support. This research has made use of the SIMBAD database operated at CDS, Strasbourg, France

A new multicompartmental reaction-diffusion modeling method links transient membrane attachment of E. coli MinE to E-ring formation

Many important cellular processes are regulated by reaction-diffusion (RD) of molecules that takes place both in the cytoplasm and on the membrane. To model and analyze such multicompartmental processes, we developed a lattice-based Monte Carlo method, Spatiocyte that supports RD in volume and surface compartments at single molecule resolution. Stochasticity in RD and the excluded volume effect brought by intracellular molecular crowding, both of which can significantly affect RD and thus, cellular processes, are also supported. We verified the method by comparing simulation results of diffusion, irreversible and reversible reactions with the predicted analytical and best available numerical solutions. Moreover, to directly compare the localization patterns of molecules in fluorescence microscopy images with simulation, we devised a visualization method that mimics the microphotography process by showing the trajectory of simulated molecules averaged according to the camera exposure time. In the rod-shaped bacterium _Escherichia coli_, the division site is suppressed at the cell poles by periodic pole-to-pole oscillations of the Min proteins (MinC, MinD and MinE) arising from carefully orchestrated RD in both cytoplasm and membrane compartments. Using Spatiocyte we could model and reproduce the _in vivo_ MinDE localization dynamics by accounting for the established properties of MinE. Our results suggest that the MinE ring, which is essential in preventing polar septation, is largely composed of MinE that is transiently attached to the membrane independently after recruited by MinD. Overall, Spatiocyte allows simulation and visualization of complex spatial and reaction-diffusion mediated cellular processes in volumes and surfaces. As we showed, it can potentially provide mechanistic insights otherwise difficult to obtain experimentally

The Distances of the Magellanic Clouds

The present status of our knowledge of the distances to the Magellanic Clouds is evaluated from a post-Hipparcos perspective. After a brief summary of the effects of structure, reddening, age and metallicity, the primary distance indicators for the Large Magellanic Cloud are reviewed: The SN 1987A ring, Cepheids, RR Lyraes, Mira variables, and Eclipsing Binaries. Distances derived via these methods are weighted and combined to produce final "best" estimates for the Magellanic Clouds distance moduli.Comment: Invited review article to appear in ``Post Hipparcos Cosmic Candles'', F. Caputo & A. Heck (Eds.), Kluwer Academic Publ., Dordrecht, in pres

The Expanding Fireball of Nova Delphini 2013

A classical nova occurs when material accreting onto the surface of a white dwarf in a close binary system ignites in a thermonuclear runaway. Complex structures observed in the ejecta at late stages could result from interactions with the companion during the common envelope phase. Alternatively, the explosion could be intrinsically bipolar, resulting from a localized ignition on the surface of the white dwarf or as a consequence of rotational distortion. Studying the structure of novae during the earliest phases is challenging because of the high spatial resolution needed to measure their small sizes. Here we report near-infrared interferometric measurements of the angular size of Nova Delphini 2013, starting from one day after the explosion and continuing with extensive time coverage during the first 43 days. Changes in the apparent expansion rate can be explained by an explosion model consisting of an optically thick core surrounded by a diffuse envelope. The optical depth of the ejected material changes as it expands. We detect an ellipticity in the light distribution, suggesting a prolate or bipolar structure that develops as early as the second day. Combining the angular expansion rate with radial velocity measurements, we derive a geometric distance to the nova of 4.54 +/- 0.59 kpc from the Sun.Comment: Published in Nature. 32 pages. Final version available at http://www.nature.com/nature/journal/v515/n7526/full/nature13834.htm

Flexible Bayesian Modelling for Nonlinear Image Registration

We describe a diffeomorphic registration algorithm that allows groups of images to be accurately aligned to a common space, which we intend to incorporate into the SPM software. The idea is to perform inference in a probabilistic graphical model that accounts for variability in both shape and appearance. The resulting framework is general and entirely unsupervised. The model is evaluated at inter-subject registration of 3D human brain scans. Here, the main modeling assumption is that individual anatomies can be generated by deforming a latent 'average' brain. The method is agnostic to imaging modality and can be applied with no prior processing. We evaluate the algorithm using freely available, manually labelled datasets. In this validation we achieve state-of-the-art results, within reasonable runtimes, against previous state-of-the-art widely used, inter-subject registration algorithms. On the unprocessed dataset, the increase in overlap score is over 17%. These results demonstrate the benefits of using informative computational anatomy frameworks for nonlinear registration.Comment: Accepted for MICCAI 202

Intravital FRAP Imaging using an E-cadherin-GFP Mouse Reveals Disease- and Drug-Dependent Dynamic Regulation of Cell-Cell Junctions in Live Tissue.

E-cadherin-mediated cell-cell junctions play a prominent role in maintaining the epithelial architecture. The disruption or deregulation of these adhesions in cancer can lead to the collapse of tumor epithelia that precedes invasion and subsequent metastasis. Here we generated an E-cadherin-GFP mouse that enables intravital photobleaching and quantification of E-cadherin mobility in live tissue without affecting normal biology. We demonstrate the broad applications of this mouse by examining E-cadherin regulation in multiple tissues, including mammary, brain, liver, and kidney tissue, while specifically monitoring E-cadherin mobility during disease progression in the pancreas. We assess E-cadherin stability in native pancreatic tissue upon genetic manipulation involving Kras and p53 or in response to anti-invasive drug treatment and gain insights into the dynamic remodeling of E-cadherin during in situ cancer progression. FRAP in the E-cadherin-GFP mouse, therefore, promises to be a valuable tool to fundamentally expand our understanding of E-cadherin-mediated events in native microenvironments

Oncogenic BRAF, unrestrained by TGFβ-receptor signalling, drives right-sided colonic tumorigenesis.

Right-sided (proximal) colorectal cancer (CRC) has a poor prognosis and a distinct mutational profile, characterized by oncogenic BRAF mutations and aberrations in mismatch repair and TGFβ signalling. Here, we describe a mouse model of right-sided colon cancer driven by oncogenic BRAF and loss of epithelial TGFβ-receptor signalling. The proximal colonic tumours that develop in this model exhibit a foetal-like progenitor phenotype (Ly6a/Sca1+) and, importantly, lack expression of Lgr5 and its associated intestinal stem cell signature. These features are recapitulated in human BRAF-mutant, right-sided CRCs and represent fundamental differences between left- and right-sided disease. Microbial-driven inflammation supports the initiation and progression of these tumours with foetal-like characteristics, consistent with their predilection for the microbe-rich right colon and their antibiotic sensitivity. While MAPK-pathway activating mutations drive this foetal-like signature via ERK-dependent activation of the transcriptional coactivator YAP, the same foetal-like transcriptional programs are also initiated by inflammation in a MAPK-independent manner. Importantly, in both contexts, epithelial TGFβ-receptor signalling is instrumental in suppressing the tumorigenic potential of these foetal-like progenitor cells

Stationary Black Holes: Uniqueness and Beyond

The spectrum of known black-hole solutions to the stationary Einstein equations has been steadily increasing, sometimes in unexpected ways. In particular, it has turned out that not all black-hole-equilibrium configurations are characterized by their mass, angular momentum and global charges. Moreover, the high degree of symmetry displayed by vacuum and electro-vacuum black-hole spacetimes ceases to exist in self-gravitating non-linear field theories. This text aims to review some developments in the subject and to discuss them in light of the uniqueness theorem for the Einstein-Maxwell system.Comment: Major update of the original version by Markus Heusler from 1998. Piotr T. Chru\'sciel and Jo\~ao Lopes Costa succeeded to this review's authorship. Significantly restructured and updated all sections; changes are too numerous to be usefully described here. The number of references increased from 186 to 32

NOTUM from Apc-mutant cells biases clonal competition to initiate cancer

The tumour suppressor APC is the most commonly mutated gene in colorectal cancer. Loss of Apc in intestinal stem cells drives the formation of adenomas in mice via increased WNT signalling1, but reduced secretion of WNT ligands increases the ability of Apc-mutant intestinal stem cells to colonize a crypt (known as fixation)2. Here we investigated how Apc-mutant cells gain a clonal advantage over wild-type counterparts to achieve fixation. We found that Apc-mutant cells are enriched for transcripts that encode several secreted WNT antagonists, with Notum being the most highly expressed. Conditioned medium from Apc-mutant cells suppressed the growth of wild-type organoids in a NOTUM-dependent manner. Furthermore, NOTUM-secreting Apc-mutant clones actively inhibited the proliferation of surrounding wild-type crypt cells and drove their differentiation, thereby outcompeting crypt cells from the niche. Genetic or pharmacological inhibition of NOTUM abrogated the ability of Apc-mutant cells to expand and form intestinal adenomas. We identify NOTUM as a key mediator during the early stages of mutation fixation that can be targeted to restore wild-type cell competitiveness and provide preventative strategies for people at a high risk of developing colorectal cancer

Hearing Loss in Stranded Odontocete Dolphins and Whales

The causes of dolphin and whale stranding can often be difficult to determine. Because toothed whales rely on echolocation for orientation and feeding, hearing deficits could lead to stranding. We report on the results of auditory evoked potential measurements from eight species of odontocete cetaceans that were found stranded or severely entangled in fishing gear during the period 2004 through 2009. Approximately 57% of the bottlenose dolphins and 36% of the rough-toothed dolphins had significant hearing deficits with a reduction in sensitivity equivalent to severe (70–90 dB) or profound (>90 dB) hearing loss in humans. The only stranded short-finned pilot whale examined had profound hearing loss. No impairments were detected in seven Risso's dolphins from three different stranding events, two pygmy killer whales, one Atlantic spotted dolphin, one spinner dolphin, or a juvenile Gervais' beaked whale. Hearing impairment could play a significant role in some cetacean stranding events, and the hearing of all cetaceans in rehabilitation should be tested