S6K1 and 4E-BP1 Are Independent Regulated and Control Cellular Growth in Bladder Cancer

Aberrant activation and mutation status of proteins in the phosphatidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) and the mitogen activated protein kinase (MAPK) signaling pathways have been linked to tumorigenesis in various tumors including urothelial carcinoma (UC). However, anti-tumor therapy with small molecule inhibitors against mTOR turned out to be less successful than expected. We characterized the molecular mechanism of this pathway in urothelial carcinoma by interfering with different molecular components using small chemical inhibitors and siRNA technology and analyzed effects on the molecular activation status, cell growth, proliferation and apoptosis. In a majority of tested cell lines constitutive activation of the PI3K was observed. Manipulation of mTOR or Akt expression or activity only regulated phosphorylation of S6K1 but not 4E-BP1. Instead, we provide evidence for an alternative mTOR independent but PI3K dependent regulation of 4E-BP1. Only the simultaneous inhibition of both S6K1 and 4E-BP1 suppressed cell growth efficiently. Crosstalk between PI3K and the MAPK signaling pathway is mediated via PI3K and indirect by S6K1 activity. Inhibition of MEK1/2 results in activation of Akt but not mTOR/S6K1 or 4E-BP1. Our data suggest that 4E-BP1 is a potential new target molecule and stratification marker for anti cancer therapy in UC and support the consideration of a multi-targeting approach against PI3K, mTORC1/2 and MAPK

Rapid divergence and expansion of the X chromosome in papaya

X chromosomes have long been thought to conserve the structure and gene content of the ancestral autosome from which the sex chromosomes evolved. We compared the recently evolved papaya sex chromosomes with a homologous autosome of a close relative, the monoecious Vasconcellea monoica, to infer changes since recombination stopped between the papaya sex chromosomes. We sequenced 12 V. monoica bacterial artificial chromosomes, 11 corresponding to the papaya X-specific region, and 1 to a papaya autosomal region. The combined V. monoica X-orthologous sequences are much shorter (1.10 Mb) than the corresponding papaya region (2.56 Mb). Given that the V. monoica genome is 41% larger than that of papaya, this finding suggests considerable expansion of the papaya X; expansion is supported by a higher repetitive sequence content of the X compared with the papaya autosomal sequence. The alignable regions include 27 transcript-encoding sequences, only 6 of which are functional X/V. monoica gene pairs. Sequence divergence from the V. monoica orthologs is almost identical for papaya X and Y alleles; the Carica-Vasconcellea split therefore occurred before the papaya sex chromosomes stopped recombining, making V. monoica a suitable outgroup for inferring changes in papaya sex chromosomes. The papaya X and the hermaphrodite-specific region of the Y(h) chromosome and V. monoica have all gained and lost genes, including a surprising amount of changes in the X

Quasar accretion disk sizes from continuum reverberation mapping in the DES standard-star fields

Measurements of the physical properties of accretion disks in active galactic nuclei are important for better understanding the growth and evolution of supermassive black holes. We present the accretion disk sizes of 22 quasars from continuum reverberation mapping with data from the Dark Energy Survey (DES) standard star fields and the supernova C fields. We construct continuum lightcurves with the \textit{griz} photometry that span five seasons of DES observations. These data sample the time variability of the quasars with a cadence as short as one day, which corresponds to a rest frame cadence that is a factor of a few higher than most previous work. We derive time lags between bands with both JAVELIN and the interpolated cross-correlation function method, and fit for accretion disk sizes using the JAVELIN Thin Disk model. These new measurements include disks around black holes with masses as small as $\sim10^7$ $M_{\odot}$, which have equivalent sizes at 2500\AA \, as small as $\sim 0.1$ light days in the rest frame. We find that most objects have accretion disk sizes consistent with the prediction of the standard thin disk model when we take disk variability into account. We have also simulated the expected yield of accretion disk measurements under various observational scenarios for the Large Synoptic Survey Telescope Deep Drilling Fields. We find that the number of disk measurements would increase significantly if the default cadence is changed from three days to two days or one day.Comment: 33 pages, 24 figure

H0LiCOW X: Spectroscopic/imaging survey and galaxy-group identification around the strong gravitational lens system WFI2033-4723

Galaxies and galaxy groups located along the line of sight towards gravitationally lensed quasars produce high-order perturbations of the gravitational potential at the lens position. When these perturbation are too large, they can induce a systematic error on $H_0$ of a few-percent if the lens system is used for cosmological inference and the perturbers are not explicitly accounted for in the lens model. In this work, we present a detailed characterization of the environment of the lens system WFI2033-4723 ($z_{\rm src} = 1.662$, $z_{\rm lens}$ = 0.6575), one of the core targets of the H0LICOW project for which we present cosmological inferences in a companion paper (Rusu et al. 2019). We use the Gemini and ESO-Very Large telescopes to measure the spectroscopic redshifts of the brightest galaxies towards the lens, and use the ESO-MUSE integral field spectrograph to measure the velocity-dispersion of the lens ($\sigma_{\rm {los}}= 250^{+15}_{-21}$ km/s) and of several nearby galaxies. In addition, we measure photometric redshifts and stellar masses of all galaxies down to $i < 23$ mag, mainly based on Dark Energy Survey imaging (DR1). Our new catalog, complemented with literature data, more than doubles the number of known galaxy spectroscopic redshifts in the direct vicinity of the lens, expanding to 116 (64) the number of spectroscopic redshifts for galaxies separated by less than 3 arcmin (2 arcmin) from the lens. Using the flexion-shift as a measure of the amplitude of the gravitational perturbation, we identify 2 galaxy groups and 3 galaxies that require specific attention in the lens models. The ESO MUSE data enable us to measure the velocity-dispersions of three of these galaxies. These results are essential for the cosmological inference analysis presented in Rusu et al. (2019).Comment: Matches the version accepted for publication by MNRAS. Note that this paper previously appeared as H0LICOW X

Brown dwarf census with the Dark Energy Survey year 3 data and the thin disc scale height of early L types

27 pages, 18 figuresIn this paper we present a catalogue of 11 745 brown dwarfs with spectral types ranging from L0 to T9, photometrically classified using data from the Dark Energy Survey (DES) year 3 release matched to the Vista Hemisphere Survey (VHS) DR3 and Wide-field Infrared Survey Explorer (WISE) data, covering ≈2400 deg2 up to iAB = 22. The classification method follows the same phototype method previously applied to SDSS-UKIDSS-WISE data. The most significant difference comes from the use of DES data instead of SDSS, which allow us to classify almost an order of magnitude more brown dwarfs than any previous search and reaching distances beyond 400 pc for the earliest types. Next, we also present and validate the GalmodBD simulation, which produces brown dwarf number counts as a function of structural parameters with realistic photometric properties of a given survey. We use this simulation to estimate the completeness and purity of our photometric LT catalogue down to iAB = 22, as well as to compare to the observed number of LT types. We put constraints on the thin disc scale height for the early L (L0–L3) population to be around 450 pc, in agreement with previous findings. For completeness, we also publish in a separate table a catalogue of 20 863 M dwarfs that passed our colour cut with spectral types greater than M6. Both the LT and the late M catalogues are found at DES release page https://des.ncsa.illinois.edu/releases/other/y3-mlt.Peer reviewedFinal Published versio

Transfer learning for galaxy morphology from one survey to another

© 2018 The Author(s). Published by Oxford University Press on behalf of the Royal Astronomical Society.Deep Learning (DL) algorithms for morphological classification of galaxies have proven very successful, mimicking (or even improving) visual classifications. However, these algorithms rely on large training samples of labelled galaxies (typically thousands of them). A key question for using DL classifications in future Big Data surveys is how much of the knowledge acquired from an existing survey can be exported to a new dataset, i.e. if the features learned by the machines are meaningful for different data. We test the performance of DL models, trained with Sloan Digital Sky Survey (SDSS) data, on Dark Energy survey (DES) using images for a sample of $\sim$5000 galaxies with a similar redshift distribution to SDSS. Applying the models directly to DES data provides a reasonable global accuracy ($\sim$ 90%), but small completeness and purity values. A fast domain adaptation step, consisting in a further training with a small DES sample of galaxies ($\sim$500-300), is enough for obtaining an accuracy > 95% and a significant improvement in the completeness and purity values. This demonstrates that, once trained with a particular dataset, machines can quickly adapt to new instrument characteristics (e.g., PSF, seeing, depth), reducing by almost one order of magnitude the necessary training sample for morphological classification. Redshift evolution effects or significant depth differences are not taken into account in this study.Peer reviewedFinal Accepted Versio

Chemical Abundance Analysis of Tucana III, the Second rr-process Enhanced Ultra-Faint Dwarf Galaxy

We present a chemical abundance analysis of four additional confirmed member stars of Tucana III, a Milky Way satellite galaxy candidate in the process of being tidally disrupted as it is accreted by the Galaxy. Two of these stars are centrally located in the core of the galaxy while the other two stars are located in the eastern and western tidal tails. The four stars have chemical abundance patterns consistent with the one previously studied star in Tucana III: they are moderately enhanced in $r$-process elements, i.e. they have $\approx +$0.4 dex. The non-neutron-capture elements generally follow trends seen in other dwarf galaxies, including a metallicity range of 0.44 dex and the expected trend in $\alpha$-elements, i.e., the lower metallicity stars have higher Ca and Ti abundance. Overall, the chemical abundance patterns of these stars suggest that Tucana III was an ultra-faint dwarf galaxy, and not a globular cluster, before being tidally disturbed. As is the case for the one other galaxy dominated by $r$-process enhanced stars, Reticulum II, Tucana III's stellar chemical abundances are consistent with pollution from ejecta produced by a binary neutron star merger, although a different $r$-process element or dilution gas mass is required to explain the abundances in these two galaxies if a neutron star merger is the sole source of $r$-process enhancement.Comment: 18 pages, 10 figures; accepted by Ap