Orbit-Based Dynamical Models of the Sombrero Galaxy (NGC 4594)

We present axisymmetric, orbit-based models to study the central black hole, stellar mass-to-light ratio, and dark matter halo of NGC 4594 (M104, the Sombrero Galaxy). For stellar kinematics, we use published high-resolution kinematics of the central region taken with the Hubble Space Telescope, newly obtained Gemini long-slit spectra of the major axis, and integral field kinematics from the SAURON instrument. At large radii, we use globular cluster kinematics to trace the mass profile and apply extra leverage to recovering the dark matter halo parameters. We find a black hole of mass M_{\bullet}=(6.6 +/- 0.4) x 10^8 M_{\odot}, and determine the stellar M/L_I=3.4 +/- 0.05 (uncertainties are the 68% confidence band marginalized over the other parameters). Our best fit dark matter halo is a cored logarithmic model with asymptotic circular speed V_c=376 +/- 12 km/s and core radius r_c= 4.7 +/- 0.6 kpc. The fraction of dark to total mass contained within the half-light radius is 0.52. Taking the bulge and disk components into account in our calculation of \sigma_e puts NGC 4594 squarely on the M-\sigma relation. We also determine that NGC 4594 lies directly on the M-L relation.Comment: 13 pages, 10 figures, accepted for publication in Ap

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

The Zwicky Transient Facility: Observing System

The Zwicky Transient Facility (ZTF) Observing System (OS) is the data collector for the ZTF project to study astrophysical phenomena in the time domain. ZTF OS is based upon the 48 inch aperture Schmidt-type design Samuel Oschin Telescope at the Palomar Observatory in Southern California. It incorporates new telescope aspheric corrector optics, dome and telescope drives, a large-format exposure shutter, a flat-field illumination system, a robotic bandpass filter exchanger, and the key element: a new 47-square-degree, 600 megapixel cryogenic CCD mosaic science camera, along with supporting equipment. The OS collects and delivers digitized survey data to the ZTF Data System (DS). Here, we describe the ZTF OS design, optical implementation, delivered image quality, detector performance, and robotic survey efficiency

The Zwicky Transient Facility: System Overview, Performance, and First Results

The Zwicky Transient Facility (ZTF) is a new optical time-domain survey that uses the Palomar 48 inch Schmidt telescope. A custom-built wide-field camera provides a 47 deg 2 field of view and 8 s readout time, yielding more than an order of magnitude improvement in survey speed relative to its predecessor survey, the Palomar Transient Factory. We describe the design and implementation of the camera and observing system. The ZTF data system at the Infrared Processing and Analysis Center provides near-real-time reduction to identify moving and varying objects. We outline the analysis pipelines, data products, and associated archive. Finally, we present on-sky performance analysis and first scientific results from commissioning and the early survey. ZTF’s public alert stream will serve as a useful precursor for that of the Large Synoptic Survey Telescope

The Zwicky Transient Facility: Science Objectives

The Zwicky Transient Facility (ZTF), a public–private enterprise, is a new time-domain survey employing a dedicated camera on the Palomar 48-inch Schmidt telescope with a 47 deg2 field of view and an 8 second readout time. It is well positioned in the development of time-domain astronomy, offering operations at 10% of the scale and style of the Large Synoptic Survey Telescope (LSST) with a single 1-m class survey telescope. The public surveys will cover the observable northern sky every three nights in g and r filters and the visible Galactic plane every night in g and r. Alerts generated by these surveys are sent in real time to brokers. A consortium of universities that provided funding (“partnership”) are undertaking several boutique surveys. The combination of these surveys producing one million alerts per night allows for exploration of transient and variable astrophysical phenomena brighter than r∼20.5 on timescales of minutes to years. We describe the primary science objectives driving ZTF, including the physics of supernovae and relativistic explosions, multi-messenger astrophysics, supernova cosmology, active galactic nuclei, and tidal disruption events, stellar variability, and solar system objects. © 2019. The Astronomical Society of the Pacific

Considerations for Physiologically Based Modeling in Liver Disease : From Nonalcoholic Fatty Liver (NAFL) to Nonalcoholic Steatohepatitis (NASH)

Nonalcoholic fatty liver disease (NAFLD), representing a clinical spectrum ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), is rapidly evolving into a global pandemic. Patients with NAFLD are burdened with high rates of metabolic syndrome-related comorbidities resulting in polypharmacy. Therefore, it is crucial to gain a better understanding of NAFLD-mediated changes in drug disposition and efficacy/toxicity. Despite extensive clinical pharmacokinetic data in cirrhosis, current knowledge concerning pharmacokinetic alterations in NAFLD, particularly at different stages of disease progression, is relatively limited. In vitro-to-in vivo extrapolation coupled with physiologically based pharmacokinetic and pharmacodynamic (IVIVE-PBPK/PD) modeling offers a promising approach for optimizing pharmacologic predictions while refining and reducing clinical studies in this population. Use of IVIVE-PBPK to predict intra-organ drug concentrations at pharmacologically relevant sites of action is particularly advantageous when it can be linked to pharmacodynamic effects. Quantitative systems pharmacology/toxicology (QSP/QST) modeling can be used to translate pharmacokinetic and pharmacodynamic data from PBPK/PD models into clinically relevant predictions of drug response and toxicity. In this review, a detailed summary of NAFLD-mediated alterations in human physiology relevant to drug absorption, distribution, metabolism, and excretion (ADME) is provided. The application of literature-derived physiologic parameters and ADME-associated protein abundance data to inform virtual NAFLD population development and facilitate PBPK/PD, QSP, and QST predictions is discussed along with current limitations of these methodologies and knowledge gaps. The proposed methodologic framework offers great potential for meaningful prediction of pharmacological outcomes in patients with NAFLD and can inform both drug development and clinical practice for this population.Peer reviewe

Initial performance of the Zwicky transient facility: a wide-fast time-domain survey

Zwicky Transient Facility is an integrated, multi-band astronomical survey system optimized for sensitivity, observing cadence, and efficiency. The key subsystem consists of a 600 megapixel CCD focal plane mounted in a flat-fielding vacuum cryostat, located at the prime focus of the 1.2-meter Samuel Oschin Telescope at Palomar Observatory. Supporting subsystems include a new 2.4-meter optical shutter assembly, a 1.35-meter diameter aspheric corrector plate, a cryostat stabilizing hexapod, a commercial robotic arm-based exchanger, three 440 millimeter width filters, four guide/focus CCDs, and dedicated optics compensating individual field curvature over each of sixteen 6k x 6k science CCDs.To optimize ZTF efficiency, all telescope and dome drives were upgraded for higher speed and acceleration, fast readout electronics were implemented, and a sophisticated robotic control system has been implemented. We present for the first time on-sky results from the recently completed ZTF including its realized optical image quality, CCD noise, and observing efficiency performance and discuss engineering challenges that have been overcome. Early scientific results from the ZTF survey are also included