Seshat: The Global History Databank

The vast amount of knowledge about past human societies has not been systematically organized and, therefore, remains inaccessible for empirically testing theories about cultural evolution and historical dynamics. For example, what evolutionary mechanisms were involved in the transition from the small-scale, uncentralized societies, in which humans lived 10,000 years ago, to the large-scale societies with an extensive division of labor, great differentials in wealth and power, and elaborate governance structures of today? Why do modern states sometimes fail to meet the basic needs of their populations? Why do economies decline, or fail to grow? In this article, we describe the structure and uses of a massive databank of historical and archaeological information, Seshat: The Global History Databank. The data that we are currently entering in Seshat will allow us and others to test theories explaining how modern societies evolved from ancestral ones, and why modern societies vary so much in their capacity to satisfy their members’ basic human needsPeer reviewedFinal Published versio

A new class of large-amplitude radial-mode hot subdwarf pulsators

Using high-cadence observations from the Zwicky Transient Facility at low Galactic latitudes, we have discovered a new class of pulsating, hot compact stars. We have found four candidates, exhibiting blue colors (g − r ≤ −0.1 mag), pulsation amplitudes of >5%, and pulsation periods of 200–475 s. Fourier transforms of the light curves show only one dominant frequency. Phase-resolved spectroscopy for three objects reveals significant radial velocity, T eff, and log(g) variations over the pulsation cycle, which are consistent with large-amplitude radial oscillations. The mean T eff and log(g) for these stars are consistent with hot subdwarf B (sdB) effective temperatures and surface gravities. We calculate evolutionary tracks using MESA and adiabatic pulsations using GYRE for low-mass, helium-core pre-white dwarfs (pre-WDs) and low-mass helium-burning stars. Comparison of low-order radial oscillation mode periods with the observed pulsation periods show better agreement with the pre-WD models. Therefore, we suggest that these new pulsators and blue large-amplitude pulsators (BLAPs) could be members of the same class of pulsators, composed of young ≈0.25–0.35 M ⊙ helium-core pre-WDs.Published versio

Phase I Study of Ipilimumab Combined with Whole Brain Radiation Therapy or Radiosurgery for Melanoma Patients with Brain Metastases

Purpose: We performed a phase I study to determine the maximum tolerable dose (MTD) and safety of ipilimumab with stereotactic radiosurgery (SRS) or whole brain radiotherapy (WBRT) in patients with brain metastases (BM) from melanoma. Methods: Based on intracranial (IC) disease burden, patients were treated with WBRT (Arm A) or SRS (Arm B). Ipilimumab starting dose was 3 mg/kg (every 3 weeks, starting on day 3 of WBRT or 2 days after SRS). Ipilimumab was escalated to 10 mg/kg using a two-stage, 3+3 design. The primary endpoint was to determine the MTD of ipilimumab combined with radiotherapy. Secondary endpoints were overall survival (OS), IC and extracranial (EC) control, progression free survival (PFS), and toxicity. This trial is regis- tered with ClinicalTrials.gov, number NCT01703507. Results: Characteristics of the 16 patients enrolled between 2011 and 2014 were: mean age, 60; median BM, 2 (1 to \u3e10); number with EC disease, 13 (81%). Treatment included WBRT (n=5), SRS (n=11), ipilimumab 3mg/kg (n=7), 10 mg/kg (n=9). Median follow-up was 8 months (Arm A) and 10.5 months (Arm B). There were 21 grade 1-2 neuro- toxic effects with no dose-limiting toxicities (DLTs). One patient experienced grade 3 neurotoxicity prior to ipilimumab administration. Ten additional grade 3 toxicities were reported with gastrointestinal (n=5, 31%) as the most common. There were no grade 4/5 toxicities. Median PFS and OS, respectively, in Arm A were 2.5 months and 8 months, and in Arm B were 2.1 months and not reached. Conclusion: Concurrent ipilimumab 10 mg/kg with SRS is safe. The WBRT arm was closed early due to slow accrual, but demonstrated safety with ipilimumab 3 mg/kg. No patient experienced DLT. Larger studies with ipilimumab 10 mg/kg and SRS are warranted

Orbital Decay in a 20 Minute Orbital Period Detached Binary with a Hydrogen-poor Low-mass White Dwarf

We report the discovery of a detached double white dwarf binary with an orbital period of ≈20.6 minutes, PTF J053332.05+020911.6. The visible object in this binary, PTF J0533+0209B, is a ≈0.17 M⊙ mass white dwarf with a helium-dominated atmosphere containing traces of hydrogen. This object exhibits ellipsoidal variations due to tidal deformation, and is the visible component in a single-lined spectroscopic binary with a velocity semi-amplitude of K_B = 618.7 ± 6.9 km s⁻¹. We have detected significant orbital decay due to the emission of gravitational radiation, and we expect that the Laser Interferometer Space Antenna (LISA) will detect this system with a signal to noise of 8.4^(+4.2)_(-3.0) after four years of operation. Because this system already has a well-determined orbital period, radial velocity semi-amplitude, temperature, atmospheric composition, surface gravity, and orbital decay rate, a LISA signal will help fully constrain the properties of this system by providing a direct measurement of its inclination. Thus, this binary demonstrates the synergy between electromagnetic and gravitational radiation for constraining the physical properties of an astrophysical object

Discovery of an intermediate-luminosity red transient in M51 and its likely dust-obscured, infrared-variable progenitor

We present the discovery of an optical transient (OT) in Messier 51, designated M51 OT2019-1 (also ZTF19aadyppr, AT 2019abn, ATLAS19bzl), by the Zwicky Transient Facility (ZTF). The OT rose over 15 days to an observed luminosity of $M_r=-13$ (${\nu}L_{\nu}=9\times10^6~L_{\odot}$), in the luminosity gap between novae and typical supernovae (SNe). Spectra during the outburst show a red continuum, Balmer emission with a velocity width of $\approx400$ km s$^{-1}$, Ca II and [Ca II] emission, and absorption features characteristic of an F-type supergiant. The spectra and multiband light curves are similar to the so-called "SN impostors" and intermediate-luminosity red transients (ILRTs). We directly identify the likely progenitor in archival Spitzer Space Telescope imaging with a $4.5~\mu$m luminosity of $M_{[4.5]}\approx-12.2$ and a $[3.6]-[4.5]$ color redder than 0.74 mag, similar to those of the prototype ILRTs SN 2008S and NGC 300 OT2008-1. Intensive monitoring of M51 with Spitzer further reveals evidence for variability of the progenitor candidate at [4.5] in the years before the OT. The progenitor is not detected in pre-outburst Hubble Space Telescope optical and near-IR images. The optical colors during outburst combined with spectroscopic temperature constraints imply a higher reddening of $E(B-V)\approx0.7$ mag and higher intrinsic luminosity of $M_r\approx-14.9$ (${\nu}L_{\nu}=5.3\times10^7~L_{\odot}$) near peak than seen in previous ILRT candidates. Moreover, the extinction estimate is higher on the rise than on the plateau, suggestive of an extended phase of circumstellar dust destruction. These results, enabled by the early discovery of M51 OT2019-1 and extensive pre-outburst archival coverage, offer new clues about the debated origins of ILRTs and may challenge the hypothesis that they arise from the electron-capture induced collapse of extreme asymptotic giant branch stars.Comment: 21 pages, 5 figures, published in ApJ

The Pentose Phosphate Pathway Regulates the Circadian Clock

The circadian clock is a ubiquitous timekeeping system that organizes the behavior and physiology of organisms over the day and night. Current models rely on transcriptional networks that coordinate circadian gene expression of thousands of transcripts. However, recent studies have uncovered phylogenetically conserved redox rhythms that can occur independently of transcriptional cycles. Here we identify the pentose phosphate pathway (PPP), a critical source of the redox cofactor NADPH, as an important regulator of redox and transcriptional oscillations. Our results show that genetic and pharmacological inhibition of the PPP prolongs the period of circadian rhythms in human cells, mouse tissues, and fruit flies. These metabolic manipulations also cause a remodeling of circadian gene expression programs that involves the circadian transcription factors BMAL1 and CLOCK, and the redox-sensitive transcription factor NRF2. Thus, the PPP regulates circadian rhythms via NADPH metabolism, suggesting a pivotal role for NADPH availability in circadian timekeeping.Peer reviewe

A New Class of Large-amplitude Radial-mode Hot Subdwarf Pulsators

Using high-cadence observations from the Zwicky Transient Facility at low Galactic latitudes, we have discovered a new class of pulsating, hot compact stars. We have found four candidates, exhibiting blue colors (g − r ≤ −0.1 mag), pulsation amplitudes of >5%, and pulsation periods of 200–475 s. Fourier transforms of the light curves show only one dominant frequency. Phase-resolved spectroscopy for three objects reveals significant radial velocity, T_(eff), and log(g) variations over the pulsation cycle, which are consistent with large-amplitude radial oscillations. The mean T_(eff) and log(g) for these stars are consistent with hot subdwarf B (sdB) effective temperatures and surface gravities. We calculate evolutionary tracks using MESA and adiabatic pulsations using GYRE for low-mass, helium-core pre-white dwarfs (pre-WDs) and low-mass helium-burning stars. Comparison of low-order radial oscillation mode periods with the observed pulsation periods show better agreement with the pre-WD models. Therefore, we suggest that these new pulsators and blue large-amplitude pulsators (BLAPs) could be members of the same class of pulsators, composed of young ≈0.25–0.35 M_⊙ helium-core pre-WDs