Quantum-mechanically correlated (entangled) states of many particles are of interest in quantum information, quantum computing and quantum metrology. Metrologically useful entangled states of large atomic ensembles have been experimentally realized [1][2][3][4][5][6][7][8][9][10], but these states display Gaussian spin distribution functions with a non-negative Wigner function. Non-Gaussian entangled states have been produced in small ensembles of ions [11,12], and very recently in large atomic ensembles [13][14][15]. Here, we generate entanglement in a large atomic ensemble via the interaction with a very weak laser pulse; remarkably, the detection of a single photon prepares several thousand atoms in an entangled state. We reconstruct a negative-valued Wigner function, an important hallmark of nonclassicality, and verify an entanglement depth (minimum number of mutually entangled atoms) of 2910 ± 190 out of 3100 atoms. This is the first time a negative Wigner function or the mutual entanglement of virtually all atoms have been attained in an ensemble containing more than a few particles. While the achieved purity of the state is slightly below the threshold for entanglement-induced metrological gain, further technical improvement should allow the generation of states that surpass this threshold, and of more complex Schrödinger cat states for quantum metrology and information processing. More generally, our results demonstrate the power of heralded methods for entanglement generation, and illustrate how the information contained in a single photon can drastically alter the quantum state of a large system.Entanglement is now recognized as a resource for secure communication, quantum information processing, and precision measurements. An important goal is the creation of entangled states of many-particle systems while retaining the ability to characterize the quantum state and validate entanglement. Entanglement can be verified in a variety of ways, with one of the strictest criteria being a negative-valued Wigner function [16,17], that necessarily implies that the entangled state has a non-Gaussian wavefunction. To date, the metrologically useful spin-squeezed states[1-10] have been produced in large ensembles. These states have Gaussian spin distributions and therefore can largely be modeled as systems with a classical source of spin noise, where quantum mechanics enters only to set the amount of Gaussian noise. Non-Gaussian states with a negative Wigner function, however, are manifestly non-classical, since the Wigner function as a quasiprobability function must remain nonnegative in the classical realm. While prior to this work a negative Wigner function had not been attained for atomic ensembles, in the optical domain, a negativevalued Wigner function has very recently been measured for states with up to 110 microwave photons [18]. Another entanglement measure is the entanglement depth [19], i.e. the minimum number of atoms that are demonstrably, but possibly weakly, entangled with one another. This paramete...

A nuclear disaster may result in exposure to potentially lethal doses of ionizing radiation (IR). Hematopoietic acute radiation syndrome (H-ARS) is characterized by severe myelosuppression, which increases the risk of infection, bleeding, and mortality. Here, we determined that activation of nuclear factor erythroid-2-related factor 2 (NRF2) signaling enhances hematopoietic stem progenitor cell (HSPC) function and mitigates IR-induced myelosuppression and mortality. Augmenting NRF2 signaling in mice, either by genetic deletion of the NRF2 inhibitor Keap1 or by pharmacological NRF2 activation with 2-trifluoromethyl-2′-methoxychalone (TMC), enhanced hematopoietic reconstitution following bone marrow transplantation (BMT). Strikingly, even 24 hours after lethal IR exposure, oral administration of TMC mitigated myelosuppression and mortality in mice. Furthermore, TMC administration to irradiated transgenic Notch reporter mice revealed activation of Notch signaling in HSPCs and enhanced HSPC expansion by increasing Jagged1 expression in BM stromal cells. Administration of a Notch inhibitor ablated the effects of TMC on hematopoietic reconstitution. Taken together, we identified a mechanism by which NRF2-mediated Notch signaling improves HSPC function and myelosuppression following IR exposure. Our data indicate that targeting this pathway may provide a countermeasure against the damaging effects of IR exposure.

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