The High-Altitude Water Cherenkov (HAWC) Observatory in M\'exico: The Primary Detector

The High-Altitude Water Cherenkov (HAWC) observatory is a second-generation continuously operated, wide field-of-view, TeV gamma-ray observatory. The HAWC observatory and its analysis techniques build on experience of the Milagro experiment in using ground-based water Cherenkov detectors for gamma-ray astronomy. HAWC is located on the Sierra Negra volcano in M\'exico at an elevation of 4100 meters above sea level. The completed HAWC observatory principal detector (HAWC) consists of 300 closely spaced water Cherenkov detectors, each equipped with four photomultiplier tubes to provide timing and charge information to reconstruct the extensive air shower energy and arrival direction. The HAWC observatory has been optimized to observe transient and steady emission from sources of gamma rays within an energy range from several hundred GeV to several hundred TeV. However, most of the air showers detected are initiated by cosmic rays, allowing studies of cosmic rays also to be performed. This paper describes the characteristics of the HAWC main array and its hardware.Comment: Accepted for publications in Nuclear Inst. and Methods in Physics Research, A (2023) 168253 ( https://www.sciencedirect.com/science/article/abs/pii/S0168900223002437 ); 39 pages, 14 Figure

Supplement: "Localization and broadband follow-up of the gravitational-wave transient GW150914" (2016, ApJL, 826, L13)

This Supplement provides supporting material for Abbott et al. (2016a). We briefly summarize past electromagnetic (EM) follow-up efforts as well as the organization and policy of the current EM follow-up program. We compare the four probability sky maps produced for the gravitational-wave transient GW150914, and provide additional details of the EM follow-up observations that were performed in the different bands

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

A gravitational-wave standard siren measurement of the Hubble constant

On 17 August 2017, the Advanced LIGO 1 and Virgo 2 detectors observed the gravitational-wave event GW170817-a strong signal from the merger of a binary neutron-star system 3 . Less than two seconds after the merger, a γ-ray burst (GRB 170817A) was detected within a region of the sky consistent with the LIGO-Virgo-derived location of the gravitational-wave source 4-6 . This sky region was subsequently observed by optical astronomy facilities 7 , resulting in the identification 8-13 of an optical transient signal within about ten arcseconds of the galaxy NGC 4993. This detection of GW170817 in both gravitational waves and electromagnetic waves represents the first 'multi-messenger' astronomical observation. Such observations enable GW170817 to be used as a 'standard siren' 14-18 (meaning that the absolute distance to the source can be determined directly from the gravitational-wave measurements) to measure the Hubble constant. This quantity represents the local expansion rate of the Universe, sets the overall scale of the Universe and is of fundamental importance to cosmology. Here we report a measurement of the Hubble constant that combines the distance to the source inferred purely from the gravitational-wave signal with the recession velocity inferred from measurements of the redshift using the electromagnetic data. In contrast to previous measurements, ours does not require the use of a cosmic 'distance ladder' 19 : the gravitational-wave analysis can be used to estimate the luminosity distance out to cosmological scales directly, without the use of intermediate astronomical distance measurements. We determine the Hubble constant to be about 70 kilometres per second per megaparsec. This value is consistent with existing measurements 20,21 , while being completely independent of them. Additional standard siren measurements from future gravitationalwave sources will enable the Hubble constant to be constrained to high precision

A gravitational-wave standard siren measurement of the Hubble constant

The detection of GW170817 (ref. 1) heralds the age of gravitational-wave multi-messenger astronomy, with the observations of gravitational-wave and electromagnetic emission from the same transient source. On 17 August 2017 the network of Advanced Laser Interferometer Gravitational-wave Observatory (LIGO)2 and Virgo3 detectors observed GW170817, a strong signal from the merger of a binary neutron-star system. Less than two seconds after the merger, a γ-ray burst event, GRB 170817A, was detected consistent with the LIGO–Virgo sky localization region4–6). The sky region was subsequently observed by optical astronomy facilities7, resulting in the identification of an optical transient signal within about 10 arcseconds of the galaxy NGC 4993 (refs 8–13). GW170817 can be used as a standard siren14–18, combining the distance inferred purely from the gravitational-wave signal with the recession velocity arising from the electromagnetic data to determine the Hubble constant. This quantity, representing the local expansion rate of the Universe, sets the overall scale of the Universe and is of fundamental importance to cosmology. Our measurements do not require any form of cosmic ‘distance ladder’19; the gravitational-wave analysis directly estimates the luminosity distance out to cosmological scales. Here we report H0 = kilometres per second per megaparsec, which is consistent with existing measurements20,21, while being completely independent of them

Localization and Broadband Follow-up of the Gravitational-wave Transient GW150914

A gravitational-wave (GW) transient was identified in data recorded by the Advanced Laser Interferometer Gravitational-wave Observatory (LIGO) detectors on 2015 September 14. The event, initially designated G184098 and later given the name GW150914, is described in detail elsewhere. By prior arrangement, preliminary estimates of the time, significance, and sky location of the event were shared with 63 teams of observers covering radio, optical, near-infrared, X-ray, and gamma-ray wavelengths with ground- and space-based facilities. In this Letter we describe the low-latency analysis of the GW data and present the sky localization of the first observed compact binary merger. We summarize the follow-up observations reported by 25 teams via private Gamma-ray Coordinates Network circulars, giving an overview of the participating facilities, the GW sky localization coverage, the timeline, and depth of the observations. As this event turned out to be a binary black hole merger, there is little expectation of a detectable electromagnetic (EM) signature. Nevertheless, this first broadband campaign to search for a counterpart of an Advanced LIGO source represents a milestone and highlights the broad capabilities of the transient astronomy community and the observing strategies that have been developed to pursue neutron star binary merger events. Detailed investigations of the EM data and results of the EM follow-up campaign are being disseminated in papers by the individual teams. </p

Multi-messenger Observations of a Binary Neutron Star Merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ∼ 1.7 {{s}} with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of {40}-8+8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 {M}ȯ . An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ∼ 40 {{Mpc}}) less than 11 hours after the merger by the One-Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ∼10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ∼ 9 and ∼ 16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC 4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta.</p

Localization and broadband follow-up of the gravitational-wave transient GW150914

A gravitational-wave transient was identified in data recorded by the Advanced LIGO detectors on 2015 September 14. The event candidate, initially designated G184098 and later given the name GW150914, is described in detail elsewhere. By prior arrangement, preliminary estimates of the time, significance, and sky location of the event were shared with 63 teams of observers covering radio, optical, near-infrared, X-ray, and gamma-ray wavelengths with ground- and space-based facilities. In this Letter we describe the low-latency analysis of the gravitational wave data and present the sky localization of the first observed compact binary merger. We summarize the follow-up observations reported by 25 teams via private Gamma-ray Coordinates Network Circulars, giving an overview of the participating facilities, the gravitational wave sky localization coverage, the timeline and depth of the observations. As this event turned out to be a binary black hole merger, there is little expectation of a detectable electromagnetic signature. Nevertheless, this first broadband campaign to search for a counterpart of an Advanced LIGO source represents a milestone and highlights the broad capabilities of the transient astronomy community and the observing strategies that have been developed to pursue neutron star binary merger events. Detailed investigations of the electromagnetic data and results of the electromagnetic follow-up campaign will be disseminated in the papers of the individual teams