The cGAS-STING pathway drives type I IFN immunopathology in COVID-19.

COVID-19, which is caused by infection with SARS-CoV-2, is characterized by lung pathology and extrapulmonary complications <sup>1,2</sup> . Type I interferons (IFNs) have an essential role in the pathogenesis of COVID-19 (refs <sup>3-5</sup> ). Although rapid induction of type I IFNs limits virus propagation, a sustained increase in the levels of type I IFNs in the late phase of the infection is associated with aberrant inflammation and poor clinical outcome <sup>5-17</sup> . Here we show that the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, which controls immunity to cytosolic DNA, is a critical driver of aberrant type I IFN responses in COVID-19 (ref. <sup>18</sup> ). Profiling COVID-19 skin manifestations, we uncover a STING-dependent type I IFN signature that is primarily mediated by macrophages adjacent to areas of endothelial cell damage. Moreover, cGAS-STING activity was detected in lung samples from patients with COVID-19 with prominent tissue destruction, and was associated with type I IFN responses. A lung-on-chip model revealed that, in addition to macrophages, infection with SARS-CoV-2 activates cGAS-STING signalling in endothelial cells through mitochondrial DNA release, which leads to cell death and type I IFN production. In mice, pharmacological inhibition of STING reduces severe lung inflammation induced by SARS-CoV-2 and improves disease outcome. Collectively, our study establishes a mechanistic basis of pathological type I IFN responses in COVID-19 and reveals a principle for the development of host-directed therapeutics

The CUORE cryostat and its bolometric detector

CUORE is a cryogenic detector that will be operated at LNGS to search for neutrinoless double beta decay (0ββ) of 130Te. The detector installation was completed in summer 2016. Before the installation, several cold runs were done to test the cryogenic system performance. In the last cold run the base temperature of 6.3mK was reached in stable condition. CUORE-0, a CUORE prototype, has proven the feasibility of CUORE, demonstrating that the target background of 0.01 counts/keV/kg/y and the energy resolution of 5 keV are within reach

Deep Underground Neutrino Experiment (DUNE), far detector technical design report, volume III: DUNE far detector technical coordination

The preponderance of matter over antimatter in the early universe, the dynamics of the supernovae that produced the heavy elements necessary for life, and whether protons eventually decay—these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our universe, its current state, and its eventual fate. The Deep Underground Neutrino Experiment (DUNE) is an international world-class experiment dedicated to addressing these questions as it searches for leptonic charge-parity symmetry violation, stands ready to capture supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector technical design report (TDR) describes the DUNE physics program and the technical designs of the single- and dual-phase DUNE liquid argon TPC far detector modules. Volume III of this TDR describes how the activities required to design, construct, fabricate, install, and commission the DUNE far detector modules are organized and managed. This volume details the organizational structures that will carry out and/or oversee the planned far detector activities safely, successfully, on time, and on budget. It presents overviews of the facilities, supporting infrastructure, and detectors for context, and it outlines the project-related functions and methodologies used by the DUNE technical coordination organization, focusing on the areas of integration engineering, technical reviews, quality assurance and control, and safety oversight. Because of its more advanced stage of development, functional examples presented in this volume focus primarily on the single-phase (SP) detector module

Neutrinoless Double Beta Decay

This White Paper, prepared for the Fundamental Symmetries, Neutrons, and Neutrinos Town Meeting related to the 2023 Nuclear Physics Long Range Plan, makes the case for double beta decay as a critical component of the future nuclear physics program. The major experimental collaborations and many theorists have endorsed this white paper

Neutrinoless Double Beta Decay

This White Paper, prepared for the Fundamental Symmetries, Neutrons, and Neutrinos Town Meeting related to the 2023 Nuclear Physics Long Range Plan, makes the case for double beta decay as a critical component of the future nuclear physics program. The major experimental collaborations and many theorists have endorsed this white paper

Neutrinoless Double Beta Decay

International audienceThis White Paper, prepared for the Fundamental Symmetries, Neutrons, and Neutrinos Town Meeting related to the 2023 Nuclear Physics Long Range Plan, makes the case for double beta decay as a critical component of the future nuclear physics program. The major experimental collaborations and many theorists have endorsed this white paper

Neutrinoless Double Beta Decay

This White Paper, prepared for the Fundamental Symmetries, Neutrons, and Neutrinos Town Meeting related to the 2023 Nuclear Physics Long Range Plan, makes the case for double beta decay as a critical component of the future nuclear physics program. The major experimental collaborations and many theorists have endorsed this white paper

Neutrinoless Double Beta Decay

This White Paper, prepared for the Fundamental Symmetries, Neutrons, and Neutrinos Town Meeting related to the 2023 Nuclear Physics Long Range Plan, makes the case for double beta decay as a critical component of the future nuclear physics program. The major experimental collaborations and many theorists have endorsed this white paper