Multi-Messenger Astrophysics with Pulsar Timing Arrays

Pulsar timing arrays (PTAs) are on the verge of detecting low-frequency gravitational waves (GWs) from supermassive black hole binaries (SMBHBs). With continued observations of a large sample of millisecond pulsars, PTAs will reach this major milestone within the next decade. Already, SMBHB candidates are being identified by electromagnetic surveys in ever-increasing numbers; upcoming surveys will enhance our ability to detect and verify candidates, and will be instrumental in identifying the host galaxies of GW sources. Multi-messenger (GW and electromagnetic) observations of SMBHBs will revolutionize our understanding of the co-evolution of SMBHs with their host galaxies, the dynamical interactions between binaries and their galactic environments, and the fundamental physics of accretion. Multi-messenger observations can also make SMBHBs 'standard sirens' for cosmological distance measurements out to $z\simeq0.5$. LIGO has already ushered in breakthrough insights in our knowledge of black holes. The multi-messenger detection of SMBHBs with PTAs will be a breakthrough in the years $2020-2030$ and beyond, and prepare us for LISA to help complete our views of black hole demographics and evolution at higher redshifts

The 16th Data Release of the Sloan Digital Sky Surveys: First Release from the APOGEE-2 Southern Survey and Full Release of eBOSS Spectra

This paper documents the 16th data release (DR16) from the Sloan Digital Sky Surveys (SDSS), the fourth and penultimate from the fourth phase (SDSS-IV). This is the first release of data from the Southern Hemisphere survey of the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2); new data from APOGEE-2 North are also included. DR16 is also notable as the final data release for the main cosmological program of the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), and all raw and reduced spectra from that project are released here. DR16 also includes all the data from the Time Domain Spectroscopic Survey and new data from the SPectroscopic IDentification of ERosita Survey programs, both of which were co-observed on eBOSS plates. DR16 has no new data from the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey (or the MaNGA Stellar Library "MaStar"). We also preview future SDSS-V operations (due to start in 2020), and summarize plans for the final SDSS-IV data release (DR17)

The 16th Data Release of the Sloan Digital Sky Surveys: First Release from the APOGEE-2 Southern Survey and Full Release of eBOSS Spectra

This paper documents the 16th data release (DR16) from the Sloan Digital Sky Surveys (SDSS), the fourth and penultimate from the fourth phase (SDSS-IV). This is the first release of data from the Southern Hemisphere survey of the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2); new data from APOGEE-2 North are also included. DR16 is also notable as the final data release for the main cosmological program of the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), and all raw and reduced spectra from that project are released here. DR16 also includes all the data from the Time Domain Spectroscopic Survey and new data from the SPectroscopic IDentification of ERosita Survey programs, both of which were co-observed on eBOSS plates. DR16 has no new data from the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey (or the MaNGA Stellar Library "MaStar"). We also preview future SDSS-V operations (due to start in 2020), and summarize plans for the final SDSS-IV data release (DR17)

The 16th Data Release of the Sloan Digital Sky Surveys : First Release from the APOGEE-2 Southern Survey and Full Release of eBOSS Spectra

This paper documents the 16th data release (DR16) from the Sloan Digital Sky Surveys (SDSS), the fourth and penultimate from the fourth phase (SDSS-IV). This is the first release of data from the Southern Hemisphere survey of the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2); new data from APOGEE-2 North are also included. DR16 is also notable as the final data release for the main cosmological program of the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), and all raw and reduced spectra from that project are released here. DR16 also includes all the data from the Time Domain Spectroscopic Survey and new data from the SPectroscopic IDentification of ERosita Survey programs, both of which were co-observed on eBOSS plates. DR16 has no new data from the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey (or the MaNGA Stellar Library "MaStar"). We also preview future SDSS-V operations (due to start in 2020), and summarize plans for the final SDSS-IV data release (DR17).Peer reviewe

The Seventeenth Data Release of the Sloan Digital Sky Surveys: Complete Release of MaNGA, MaStar and APOGEE-2 Data

This paper documents the seventeenth data release (DR17) from the Sloan Digital Sky Surveys; the fifth and final release from the fourth phase (SDSS-IV). DR17 contains the complete release of the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey, which reached its goal of surveying over 10,000 nearby galaxies. The complete release of the MaNGA Stellar Library (MaStar) accompanies this data, providing observations of almost 30,000 stars through the MaNGA instrument during bright time. DR17 also contains the complete release of the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) survey which publicly releases infra-red spectra of over 650,000 stars. The main sample from the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), as well as the sub-survey Time Domain Spectroscopic Survey (TDSS) data were fully released in DR16. New single-fiber optical spectroscopy released in DR17 is from the SPectroscipic IDentification of ERosita Survey (SPIDERS) sub-survey and the eBOSS-RM program. Along with the primary data sets, DR17 includes 25 new or updated Value Added Catalogs (VACs). This paper concludes the release of SDSS-IV survey data. SDSS continues into its fifth phase with observations already underway for the Milky Way Mapper (MWM), Local Volume Mapper (LVM) and Black Hole Mapper (BHM) surveys

ngVLA Key Science Goal 5 Understanding the Formation and Evolution of Black Holes in the Era of Multi-Messenger Astronomy

The next-generation Very Large Array (ngVLA) will be a powerful telescope for finding and studying black holes across the entire mass range. High-resolution imaging abilities will allow the separation of low-luminosity black holes in the local Universe from background sources, thereby providing critical constraints on the mass function, formation, and growth of black holes. Its combination of sensitivity and angular resolution will provide new constraints on the physics of black hole accretion and jet formation. Combined with facilities across the spectrum and gravitational wave observatories, the ngVLA will provide crucial constraints on the interaction of black holes with their environments, with specific implications for the relationship between evolution of galaxies and the emission of gravitational waves from in-spiraling supermassive black holes and potential implications for stellar mass and intermediate mass black holes. The ngVLA will identify the radio counterparts to transient sources discovered by electromagnetic, gravitational wave, and neutrino observatories, and its high-resolution, fast-mapping capabilities will make it the preferred instrument to pinpoint electromagnetic counterparts to events such as supermassive black hole mergers. The National Radio Astronomy Observatory is a facility of the National Science Foundation operated under cooperative agreement by Associated Universities, Inc. Part of this research was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration

Global urban environmental change drives adaptation in white clover

Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale

A substitution mutation in a conserved domain of mammalian acetate-dependent acetyl CoA synthetase 2 results in destabilized protein and impaired HIF-2 signaling.

The response to environmental stresses by eukaryotic organisms includes activation of protective biological mechanisms, orchestrated in part by transcriptional regulators. The tri-member Hypoxia Inducible Factor (HIF) family of DNA-binding transcription factors include HIF-2, which is activated under conditions of oxygen or glucose deprivation. Although oxygen-dependent protein degradation is a key mechanism by which HIF-1 and HIF-2 activity is regulated, HIF-2 is also influenced substantially by the coupled action of acetylation and deacetylation. The acetylation/deacetylation process that HIF-2 undergoes employs a specific acetyltransferase and deacetylase. Likewise, the supply of the acetyl donor, acetyl CoA, used for HIF-2 acetylation originates from a specific acetyl CoA generator, acetate-dependent acetyl CoA synthetase 2 (Acss2). Although Acss2 is predominantly cytosolic, a subset of the Acss2 cellular pool is enriched in the nucleus following oxygen or glucose deprivation. Prevention of nuclear localization by a directed mutation in a putative nuclear localization signal in Acss2 abrogates HIF-2 acetylation and blunts HIF-2 dependent signaling as well as flank tumor growth for knockdown/rescue cancer cells expressing ectopic Acss2. In this study, we report generation of a novel mouse strain using CRISPR/Cas9 mutagenesis that express this mutant Acss2 allele in the mouse germline. The homozygous mutant mice have impaired induction of the canonical HIF-2 target gene erythropoietin and blunted recovery from acute anemia. Surprisingly, Acss2 protein levels are dramatically reduced in these mutant mice. Functional studies investigating the basis for this phenotype reveal multiple protein instability domains in the Acss2 carboxy terminus. The findings described herein may be of relevance in the regulation of native Acss2 protein as well as for humans carrying missense mutations in these domains

Characterization of intraocular tumors arising in transgenic mice. Invest Ophthalmol Vis Sci.

Purpose. To characterize intraocular tumors that arise by in situ transformation in the choroidretinal pigment epithelium (RPE) in transgenic mice bearing the SV40 oncogene under the control of the mouse tyrosinase promoter. Methods. Tumors from TySV40 transgenic mice were characterized in vivo and in vitro by immunohistology, compound microscopy, and electron microscopy. Tumor cell lines were established and characterized for growth and metastatic potential in the eyes of nude mice. Results. On light microscopy, ocular tumors were predominantly epithelioid, although occasional clusters of spindle cells were also present. Transmission electron microscopy revealed the presence of numerous basal infoldings and abundant multilaminated basement membranes on the ocular tumors. Tumors stained with antibodies to melanoma-associated antigens, gangliosides GD2 and GD3, and the SV40 T antigen. Radiolabeled transgenic tumor cells preferentially localized in the liver after intravenous injection in normal mice. Intracamerally transplanted transgenic tumors metastasized from the eyes to the livers of nude mice. Conclusions. In TySV40 transgenic mice, intraocular tumors develop that arise at the choroid-RPE interface, and they display morphologic and ultrastructural features consistent with RPE carcinomas. However, the transgenic tumors express melanoma-associated antigens and a propensity to metastasize to the liver, two features characteristic of uveal melanomas. The TySV40 transgenic murine tumors represent potentially useful tools for investigations into the biology and metastasis of intraocular neoplasms. Invest Ophthalmol Vis Sci. 1994; 35:3533-3539. Uveal melanoma is the most common primary intraocular neoplasm in adults. 1 The management of human uveal melanoma has received increased attention because the natural history of uveal tumors is poorly understood and more effective therapeutic modalities for preventing and treating metastases arising from uveal melanoma are desperately needed. Various animal models of intraocular melanoma have been employed to develop and analyze therapeutic modalities for managing the human counterpart. 2 However, the overwhelming majority of experimental studies have relied on the intracameral transplantation of cu- 10, 1994; revised March 15, 1994; accepted March 25, 1994. Proprietary interest category: N. Reprint requests: Dr. Jerry Y. Niederkorn, Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas 75235. taneous melanomas, often involving histoincompatible donor-host combinations. Therefore, a wide variety of investigations relating to the natural history, metastasis, and evaluation of therapeutic modalities would benefit from an animal model in which tumors arise by in situ transformation within the eye of an inbred rodent. This article reports the characterization of a transgenic mouse model in which intraocular tumors arise by in situ transformation by the transforming genes (T,t) of simian virus 40 (SV40) within the choroid-retinal pigment epithelium (RPE). Although this model, like its predecessors, has some shortcomings, it offers unique advantages for studies on the metastasis of intraocular tumors. MATERIALS AND METHODS Development of Transgenic Mice and Tumor Cell Lines Three albino transgenic FVB/N (H-2 q ) mouse lines, designated TySV40 124, TySV40 126, and TySV40 99

SRC-2-mediated coactivation of anti-tumorigenic target genes suppresses MYC-induced liver cancer

<div><p>Hepatocellular carcinoma (HCC) is the fifth most common solid tumor in the world and the third leading cause of cancer-associated deaths. A <i>Sleeping Beauty</i>-mediated transposon mutagenesis screen previously identified mutations that cooperate with MYC to accelerate liver tumorigenesis. This revealed a tumor suppressor role for <i>Steroid Receptor Coactivator 2</i>/<i>Nuclear Receptor Coactivator 2</i> (<i>Src-2</i>/<i>Ncoa2</i>) in liver cancer. In contrast, SRC-2 promotes survival and metastasis in prostate cancer cells, suggesting a tissue-specific and context-dependent role for SRC-2 in tumorigenesis. To determine if genetic loss of SRC-2 is sufficient to accelerate MYC-mediated liver tumorigenesis, we bred <i>Src-2</i>^<i>-/-</i> mice with a MYC-induced liver tumor model and observed a significant increase in liver tumor burden. RNA sequencing of liver tumors and <i>in vivo</i> chromatin immunoprecipitation assays revealed a set of direct target genes that are bound by SRC-2 and exhibit downregulated expression in <i>Src-2</i>^<i>-/-</i> liver tumors. We demonstrate that activation of <i>SHP (Small Heterodimer Partner)</i>, <i>DKK4</i> (<i>Dickkopf-4)</i>, and <i>CADM4 (Cell Adhesion Molecule 4)</i> by SRC-2 suppresses tumorigenesis <i>in vitro</i> and <i>in vivo</i>. These studies suggest that SRC-2 may exhibit oncogenic or tumor suppressor activity depending on the target genes and nuclear receptors that are expressed in distinct tissues and illuminate the mechanisms of tumor suppression by SRC-2 in liver.</p></div