A Comprehensive Archival Search for Counterparts to Ultra-Compact High Velocity Clouds: Five Local Volume Dwarf Galaxies

We report five Local Volume dwarf galaxies (two of which are presented here for the first time) uncovered during a comprehensive archival search for optical counterparts to ultra-compact high velocity clouds (UCHVCs). The UCHVC population of HI clouds are thought to be candidate gas-rich, low mass halos at the edge of the Local Group and beyond, but no comprehensive search for stellar counterparts to these systems has been presented. Careful visual inspection of all publicly available optical and ultraviolet imaging at the position of the UCHVCs revealed six blue, diffuse counterparts with a morphology consistent with a faint dwarf galaxy beyond the Local Group. Optical spectroscopy of all six candidate dwarf counterparts show that five have an H$\alpha$-derived velocity consistent with the coincident HI cloud, confirming their association, the sixth diffuse counterpart is likely a background object. The size and luminosity of the UCHVC dwarfs is consistent with other known Local Volume dwarf irregular galaxies. The gas fraction ($M_{HI}/M_{star}$) of the five dwarfs are generally consistent with that of dwarf irregular galaxies in the Local Volume, although ALFALFA-Dw1 (associated with ALFALFA UCHVC HVC274.68+74.70$-$123) has a very high $M_{HI}/M_{star}$$\sim$40. Despite the heterogenous nature of our search, we demonstrate that the current dwarf companions to UCHVCs are at the edge of detectability due to their low surface brightness, and that deeper searches are likely to find more stellar systems. If more sensitive searches do not reveal further stellar counterparts to UCHVCs, then the dearth of such systems around the Local Group may be in conflict with $\Lambda$CDM simulations.Comment: 18 pages, 4 tables, 4 figures, ApJ Accepte

Core shell lipid-polymer hybrid nanoparticles with combined docetaxel and molecular targeted therapy for the treatment of metastatic prostate cancer

Many prostate cancers relapse after initial chemotherapy treatment. Combining molecular and chemotherapy together with encapsulation of drugs in nanocarriers provides effective drug delivery and toxicity reduction. We developed core shell lipid-polymer hybrid nanoparticles (CSLPHNPs) with poly (lactic-co-glycolic acid) (PLGA) core and lipid layer containing docetaxel and clinically used inhibitor of sphingosine kinase 1 (SK1) FTY720 (fingolimod). We show for the first time that FTY720 (both free and in CSLPHNPs) re-sensitizes castrate resistant prostate cancer cells and tumors to docetaxel, allowing a four-fold reduction in effective dose. Our CSLPHNPs showed high serum stability and a long shelf life. CSLPHNPs demonstrated a steady uptake by tumor cells, sustained intracellular drug release and in vitro efficacy superior to free therapies. In a mouse model of human prostate cancer, CSLPHNPs showed excellent tumor targeting and significantly lower side effects compared to free drugs, importantly, reversing lymphopenia induced by FTY720. Overall, we demonstrate that nanoparticle encapsulation can improve targeting, provide low off-target toxicity and most importantly reduce FTY720-induced lymphopenia, suggesting its potential use in clinical cancer treatment

LSST Science Book, Version 2.0

A survey that can cover the sky in optical bands over wide fields to faint magnitudes with a fast cadence will enable many of the exciting science opportunities of the next decade. The Large Synoptic Survey Telescope (LSST) will have an effective aperture of 6.7 meters and an imaging camera with field of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over 20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a total point-source depth of r~27.5. The LSST Science Book describes the basic parameters of the LSST hardware, software, and observing plans. The book discusses educational and outreach opportunities, then goes on to describe a broad range of science that LSST will revolutionize: mapping the inner and outer Solar System, stellar populations in the Milky Way and nearby galaxies, the structure of the Milky Way disk and halo and other objects in the Local Volume, transient and variable objects both at low and high redshift, and the properties of normal and active galaxies at low and high redshift. It then turns to far-field cosmological topics, exploring properties of supernovae to z~1, strong and weak lensing, the large-scale distribution of galaxies and baryon oscillations, and how these different probes may be combined to constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at http://www.lsst.org/lsst/sciboo

Multiwavelength observations of V407 Lupi (ASASSN-16kt) --- a very fast nova erupting in an intermediate polar

We present a detailed study of the 2016 eruption of nova V407 Lupi (ASASSN-16kt), including optical, near-infrared, X-ray, and ultraviolet data from SALT, SMARTS, SOAR, Chandra, Swift, and XMM-Newton. Timing analysis of the multiwavelength light-curves shows that, from 168 days post-eruption and for the duration of the X-ray supersoft source phase, two periods at 565 s and 3.57 h are detected. We suggest that these are the rotational period of the white dwarf and the orbital period of the binary, respectively, and that the system is likely to be an intermediate polar. The optical light-curve decline was very fast ($t_2 \leq$ 2.9 d), suggesting that the white dwarf is likely massive ($\gtrsim 1.25$ M$_{\odot}$). The optical spectra obtained during the X-ray supersoft source phase exhibit narrow, complex, and moving emission lines of He II, also characteristics of magnetic cataclysmic variables. The optical and X-ray data show evidence for accretion resumption while the X-ray supersoft source is still on, possibly extending its duration

Predicting Novel Binding Modes of Agonists to β Adrenergic Receptors Using All-Atom Molecular Dynamics Simulations

Understanding the binding mode of agonists to adrenergic receptors is crucial to enabling improved rational design of new therapeutic agents. However, so far the high conformational flexibility of G protein-coupled receptors has been an obstacle to obtaining structural information on agonist binding at atomic resolution. In this study, we report microsecond classical molecular dynamics simulations of β1 and β2 adrenergic receptors bound to the full agonist isoprenaline and in their unliganded form. These simulations show a novel agonist binding mode that differs from the one found for antagonists in the crystal structures and from the docking poses reported by in silico docking studies performed on rigid receptors. Internal water molecules contribute to the stabilization of novel interactions between ligand and receptor, both at the interface of helices V and VI with the catechol group of isoprenaline as well as at the interface of helices III and VII with the ethanolamine moiety of the ligand. Despite the fact that the characteristic N-C-C-OH motif is identical in the co-crystallized ligands and in the full agonist isoprenaline, the interaction network between this group and the anchor site formed by Asp(3.32) and Asn(7.39) is substantially different between agonists and inverse agonists/antagonists due to two water molecules that enter the cavity and contribute to the stabilization of a novel network of interactions. These new binding poses, together with observed conformational changes in the extracellular loops, suggest possible determinants of receptor specificity

Hubble Space Telescope Imaging of Globular Cluster Candidates in Low Surface Brightness Dwarf Galaxies

Fifty-seven nearby low surface brightness dwarf galaxies were searched for globular cluster candidates (GCCs) using Hubble Space Telescope WFPC2 imaging in V and I. The sample consists of 18 dwarf spheroidal (dSph), 36 irregular (dIrr), and 3 "transition" type (dIrr/dSph) galaxies with angular sizes less than 3.7 kpc situated at distances 2-6 Mpc in the field and in the nearby groups: M81, Centaurus A, Sculptor, Canes Venatici I cloud. We find that ~50% of dSph, dIrr/dSph, and dIrr galaxies contain GCCs. The fraction of GCCs located near the center of dwarf spheroidal galaxies is >2 times higher than that for dIrrs. The mean integral color of GCCs in dSphs, V-I = 1.04+/-0.16 mag, coincides with the corresponding value for Galactic globular clusters and is similar to the blue globular cluster sub-populations in massive early-type galaxies. The color distribution for GCCs in dIrrs shows a clear bimodality with peaks near V-I = 0.5 and 1.0 mag. Blue GCCs are presumably young with ages t < 1 Gyr, while the red GCC population is likely to be older. The detected GCCs have absolute visual magnitudes between M_V = -10 and -5 mag. We find indications for an excess population of faint GCCs with M_V > -6.5 mag in both dSph and dIrr galaxies, reminiscent of excess populations of faint globular clusters in nearby Local Group spiral galaxies. The measurement of structural parameters using King-profile fitting reveals that most GCCs have structural parameters similar to extended outer halo globular clusters in the Milky Way and M31, as well as the recently discovered population of "faint fuzzy" clusters in nearby lenticular galaxies.Comment: A&A accepted, 17 page

The MAVERIC Survey: A Red Straggler Binary with an Invisible Companion in the Galactic Globular Cluster M10

We present the discovery and characterization of a radio-bright binary in the Galactic globular cluster M10. First identified in deep radio continuum data from the Karl G. Jansky Very Large Array, M10-VLA1 has a flux density of 27 ± 4 μJy at 7.4 GHz and a flat-to-inverted radio spectrum. Chandra imaging shows an X-ray source with L X ≈ 1031 erg s−1 matching the location of the radio source. This places M10-VLA1 within the scatter of the radio-X-ray luminosity correlation for quiescent stellar-mass black holes, and a black hole X-ray binary is a viable explanation for this system. The radio and X-ray properties of the source disfavor, but do not rule out, identification as an accreting neutron star or white dwarf system. Optical imaging from the Hubble Space Telescope and spectroscopy from the SOAR telescope show that the system has an orbital period of 3.339 days and an unusual "red straggler" component: an evolved star found redward of the M10 red giant branch. These data also show UV/optical variability and double-peaked Hα emission characteristic of an accretion disk. However, SOAR spectroscopic monitoring reveals that the velocity semi-amplitude of the red straggler is low. We conclude that M10-VLA1 is most likely either a quiescent black hole X-ray binary with a rather face-on (i < 4°) orientation or an unusual flaring RS Canum Venaticorum variable-type active binary, and discuss future observations that could distinguish between these possibilities

The Gravity Collective: A Search for the Electromagnetic Counterpart to the Neutron Star-Black Hole Merger GW190814

We present optical follow-up imaging obtained with the Katzman Automatic Imaging Telescope, Las Cumbres Observatory Global Telescope Network, Nickel Telescope, Swope Telescope, and Thacher Telescope of the LIGO/Virgo gravitational wave (GW) signal from the neutron star-black hole (NSBH) merger GW190814. We searched the GW190814 localization region (19 deg$^{2}$ for the 90th percentile best localization), covering a total of 51 deg$^{2}$ and 94.6% of the two-dimensional localization region. Analyzing the properties of 189 transients that we consider as candidate counterparts to the NSBH merger, including their localizations, discovery times from merger, optical spectra, likely host-galaxy redshifts, and photometric evolution, we conclude that none of these objects are likely to be associated with GW190814. Based on this finding, we consider the likely optical properties of an electromagnetic counterpart to GW190814, including possible kilonovae and short gamma-ray burst afterglows. Using the joint limits from our follow-up imaging, we conclude that a counterpart with an $r$-band decline rate of 0.68 mag day$^{-1}$, similar to the kilonova AT 2017gfo, could peak at an absolute magnitude of at most $-17.8$ mag (50% confidence). Our data are not constraining for ''red'' kilonovae and rule out ''blue'' kilonovae with $M>0.5 M_{\odot}$ (30% confidence). We strongly rule out all known types of short gamma-ray burst afterglows with viewing angles $<$17$^{\circ}$ assuming an initial jet opening angle of $\sim$$5.2^{\circ}$ and explosion energies and circumburst densities similar to afterglows explored in the literature. Finally, we explore the possibility that GW190814 merged in the disk of an active galactic nucleus, of which we find four in the localization region, but we do not find any candidate counterparts among these sources.Comment: 86 pages, 9 figure