3,328 research outputs found

    Cooperativity of Rb, Brca1, and p53 in malignant breast cancer evolution

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    Breast cancers that are triple-negative for the clinical markers ESR1, PGR, and HER2 typically belong to the Basal-like molecular subtype. Defective Rb, p53, and Brca1 pathways are each associated with triple-negative and Basal-like subtypes. Our mouse genetic studies demonstrate that the combined inactivation of Rb and p53 pathways is sufficient to suppress the physiological cell death of mammary involution. Furthermore, concomitant inactivation of all three pathways in mammary epithelium has an additive effect on tumor latency and predisposes highly penetrant, metastatic adenocarcinomas. The tumors are poorly differentiated and have histologic features that are common among human Brca1-mutated tumors, including heterogeneous morphology, metaplasia, and necrosis. Gene expression analyses demonstrate that the tumors share attributes of both Basal-like and Claudin-low signatures, two molecular subtypes encompassed by the broader, triple-negative class defined by clinical markers

    Allochthonous sources and dynamic cycling of ocean dissolved organic carbon revealed by carbon isotopes

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    Author Posting. © American Geophysical Union, 2017. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geophysical Research Letters 44 (2017): 2407–2415, doi:10.1002/2016GL071348.We present concentration and isotopic profiles of total, size, and polarity fractionated dissolved organic carbon (DOC) from Station ALOHA (A Long-term Oligotrophic Habitat Assessment), an oligotrophic site in the North Pacific Ocean. The data show that, between the surface and 3500 m, low molecular weight (LMW) hydrophilic DOC, LMW hydrophobic DOC, and high molecular weight (HMW) DOC constitute 22–33%, 45–52%, and 23–35% of DOC, respectively. LMW hydrophilic DOC is more isotopically depleted (δ13C of −23.9‰ to −31.5‰ and Δ14C of −304‰ to −795‰; mean age of 2850 to 15000 years) than the LMW hydrophobic DOC (δ13C of −22‰ to −23‰ and Δ14C of −270‰ to −568‰; 2470 to 6680 years) and HMW DOC (δ13C of ~−21‰ and Δ14C of −24‰ to −294‰; 135–2700 years). Our analyses suggest that a large fraction of DOC may be derived from allochthonous sources such as terrestrial and hydrothermal DOC and cycle on much longer time scales of >10000 years or enter the ocean as preaged carbon.NSF Cooperative Agreement for the Operation of a National Ocean Sciences Accelerator Mass Spectrometry Facility Grant Number: OCE-0753487; Gordon and Betty Moore Foundation Grant Numbers: GBMF3298, GBMF3794; Simons Foundation Grant Number: 3291082017-09-0

    The Heparan Sulfate Proteoglycans Dally-like and Syndecan Have Distinct Functions in Axon Guidance and Visual-System Assembly in Drosophila

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    SummaryHeparan sulfate proteoglycans (HSPGs), a class of glycosaminoglycan-modified proteins, control diverse patterning events via their regulation of growth-factor signaling and morphogen distribution [1]. In C. elegans, zebrafish, and the mouse, heparan sulfate (HS) biosynthesis is required for normal axon guidance [2–4], and mutations affecting Syndecan (Sdc), a transmembrane HSPG, disrupt axon guidance in Drosophila embryos [5, 6]. Glypicans, a family of glycosylphosphatidylinositol (GPI)-linked HSPGs, are expressed on axons and growth cones in vertebrates, but their role in axon guidance has not been determined [7, 8]. We demonstrate here that the Drosophila glypican Dally-like protein (Dlp) is required for proper axon guidance and visual-system function. Mosaic studies revealed that Dlp is necessary in both the retina and the brain for different aspects of visual-system assembly. Sdc mutants also showed axon guidance and visual-system defects, some that overlap with dlp and others that are unique. dlp+ transgenes were able to rescue some sdc visual-system phenotypes, but sdc+ transgenes were ineffective in rescuing dlp abnormalities. Together, these findings suggest that in some contexts HS chains provide the biologically critical component, whereas in others the structure of the protein core is also essential

    Extinction Corrected Star Formation Rates Empirically Derived from Ultraviolet-Optical Colors

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    Using a sample of galaxies from the Sloan Digital Sky Survey spectroscopic catalog with measured star-formation rates (SFRs) and ultraviolet (UV) photometry from the GALEX Medium Imaging Survey, we derived empirical linear correlations between the SFR to UV luminosity ratio and the UV-optical colors of blue sequence galaxies. The relations provide a simple prescription to correct UV data for dust attenuation that best reconciles the SFRs derived from UV and emission line data. The method breaks down for the red sequence population as well as for very blue galaxies such as the local ``supercompact'' UV luminous galaxies and the majority of high redshift Lyman Break Galaxies which form a low attenuation sequence of their own.Comment: 20 pages, 11 figures, accepted for publication in the ApJS GALEX special issu

    The Star Formation and Extinction Co-Evolution of UV-Selected Galaxies over 0.05<z<1.2

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    We use a new stacking technique to obtain mean mid IR and far IR to far UV flux ratios over the rest near-UV/near-IR color-magnitude diagram. We employ COMBO-17 redshifts and COMBO-17 optical, GALEX far and near UV, Spitzer IRAC and MIPS Mid IR photometry. This technique permits us to probe infrared excess (IRX), the ratio of far IR to far UV luminosity, and specific star formation rate (SSFR) and their co-evolution over two orders of magnitude of stellar mass and redshift 0.1<z<1.2. We find that the SSFR and the characteristic mass (M_0) above which the SSFR drops increase with redshift (downsizing). At any given epoch, IRX is an increasing function of mass up to M_0. Above this mass IRX falls, suggesting gas exhaustion. In a given mass bin below M_0 IRX increases with time in a fashion consistent with enrichment. We interpret these trends using a simple model with a Schmidt-Kennicutt law and extinction that tracks gas density and enrichment. We find that the average IRX and SSFR follows a galaxy age parameter which is determined mainly by the galaxy mass and time since formation. We conclude that blue sequence galaxies have properties which show simple, systematic trends with mass and time such as the steady build-up of heavy elements in the interstellar media of evolving galaxies and the exhaustion of gas in galaxies that are evolving off the blue sequence. The IRX represents a tool for selecting galaxies at various stages of evolution.Comment: Accepted for publication in GALEX Special Ap.J.Suppl., December, 200

    Ultraviolet through Infrared Spectral Energy Distributions from 1000 SDSS Galaxies: Dust Attenuation

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    The meaningful comparison of models of galaxy evolution to observations is critically dependent on the accurate treatment of dust attenuation. To investigate dust absorption and emission in galaxies we have assembled a sample of ~1000 galaxies with ultraviolet (UV) through infrared (IR) photometry from GALEX, SDSS, and Spitzer and optical spectroscopy from SDSS. The ratio of IR to UV emission (IRX) is used to constrain the dust attenuation in galaxies. We use the 4000A break as a robust and useful, although coarse, indicator of star formation history (SFH). We examine the relationship between IRX and the UV spectral slope (a common attenuation indicator at high-redshift) and find little dependence of the scatter on 4000A break strength. We construct average UV through far-IR spectral energy distributions (SEDs) for different ranges of IRX, 4000A break strength, and stellar mass (M_*) to show the variation of the entire SED with these parameters. When binned simultaneously by IRX, 4000A break strength, and M_* these SEDs allow us to determine a low resolution average attenuation curve for different ranges of M_*. The attenuation curves thus derived are consistent with a lambda^{-0.7} attenuation law, and we find no significant variations with M_*. Finally, we show the relationship between IRX and the global stellar mass surface density and gas-phase-metallicity. Among star forming galaxies we find a strong correlation between IRX and stellar mass surface density, even at constant metallicity, a result that is closely linked to the well-known correlation between IRX and star-formation rate.Comment: 12 pages, 8 figures, 2 tables, appearing in the Dec 2007 GALEX special issue of ApJ Supp (29 papers

    Broiler Chickens as Source of Human Fluoroquinolone-Resistant Escherichia coli, Iceland

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    To investigate feed as a source for fluoroquinolone-resistant Escherichia coli in broiler chickens, we compared antimicrobial drug–resistant E. coli from broiler feed and broilers with ciprofloxacin-resistant human clinical isolates by using pulsed-field gel electrophoresis. Feed was implicated as a source for ciprofloxacin-resistant broiler-derived E. coli and broilers as a source for ciprofloxacin-resistant human-derived E. coli

    The Young and the Dustless: Interpreting Radio Observations of UltraViolet Luminous Galaxies

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    Ultraviolet Luminous Galaxies (UVLGs) have been identified as intensely star-forming, nearby galaxies. A subset of these, the supercompact UVLGs, are believed to be local analogs of high redshift Lyman Break Galaxies. Here we investigate the radio continuum properties of this important population for the first time. We have observed 42 supercompact UVLGs with the VLA, all of which have extensive coverage in the UV/optical by GALEX and SDSS. Our analysis includes comparison samples of multiwavelength data from the Spitzer First Look Survey and from the SDSS-Galex matched catalogs. In addition we have Spitzer MIPS data for 24 of our galaxies and find that they fall on the radio-FIR correlation of normal star-forming galaxies. We find that our galaxies have lower radio-to-UV ratios and lower Balmer decrements than other local galaxies with similar (high) star formation rates. Optical spectra show they have lower Dn(4000) and HdeltaA indices, higher Hbeta emission-line equivalents widths, and higher [OIII]5007/Hbeta emission-line ratios than normal star forming galaxies. Comparing these results to galaxy spectral evolution models we conclude that supercompact UVLGs are distinguished from normal star forming galaxies firstly by their high specific star formation rates. Moreover, compared to other types of galaxies with similar star formation rates, they have significantly less dust attenuation. In both regards they are similar to Lyman Break Galaxies. This suggests that the process that causes star formation in the supercompact UVLGs differs from other local star forming galaxies, but may be similar to Lyman Break Galaxies.Comment: 37 pages, 13 figures, accepted and scheduled to appear in ApJS December 2007 (GALEX Special Issue

    Conversion between Triplet Pair States Is Controlled by Molecular Coupling in Pentadithiophene Thin Films

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    In singlet fission (SF) the initially formed correlated triplet pair state, 1(TT), may evolve toward independent triplet excitons or higher spin states of the (TT) species. The latter result is often considered undesirable from a light harvesting perspective but may be attractive for quantum information sciences (QIS) applications, as the final exciton pair can be spin-entangled and magnetically active with relatively long room temperature decoherence times. In this study we use ultrafast transient absorption (TA) and time-resolved electron paramagnetic resonance (TR-EPR) spectroscopy to monitor SF and triplet pair evolution in a series of alkyl silyl-functionalized pentadithiophene (PDT) thin films designed with systematically varying pairwise and long-range molecular interactions between PDT chromophores. The lifetime of the (TT) species varies from 40 ns to 1.5 μs, the latter of which is associated with extremely weak intermolecular coupling, sharp optical spectroscopic features, and complex TR-EPR spectra that are composed of a mixture of triplet and quintet-like features. On the other hand, more tightly coupled films produce broader transient optical spectra but simpler TR-EPR spectra consistent with significant population in 5(TT)0. These distinctions are rationalized through the role of exciton diffusion and predictions of TT state mixing with low exchange coupling J versus pure spin substate population with larger J. The connection between population evolution using electronic and spin spectroscopies enables assignments that provide a more detailed picture of triplet pair evolution than previously presented and provides critical guidance for designing molecular QIS systems based on light-induced spin coherence
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