Since the two qubits are encoded in identical bosons, the full two-particle wavefunction must be symmetric under particle exchange, e.g.,, where the two atoms are labelled 1 and 2. (In the merged trap, the subscripts L and R are replaced by e and g, , and an independent 1D lattice along the vertical direction. By controlling the laser polarization, the unit cell of the 2D lattice can be continuously changed between single-well (λ-lattice) or double-well (λ/2-lattice)configurations (see Fig. 1a), where λ=816 nm. We start with a magnetically trapped We can prepare every pair of atoms in any non-entangled two-qubit state by selectively addressing the atoms in the L and R sites. We exploit the spin-dependence of the potential, which can be manipulated through the same polarization control used to adjust the lattice topology 2,12 . We first induce a state-dependence in the optical potential that produces an effective magnetic field gradient between the two adjacent sites of the double well. This introduces a differential shift The > 10 ms decay of the swap oscillations in Fig. 3 , but there the underlying noise arises from the inherent fluctuating background of nuclear spins. In contrast, here the inhomogeneous broadening arises

Exposure of rats to hypoxia (7% O2Low cellular oxygen tension is a feature of both physiological conditions, such as adaptations to high altitude and physical endurance exercise (1), and pathophysiological conditions including ischemia, fibrosis (2), and neoplasia (3). Mammalian cells respond to hypoxia in part by increased expression of several genes that encode both tissue-specific and ubiquitous proteins (4). These proteins participate in diverse biological processes including erythropoiesis, which enhances the oxygen carrying capacity of the blood; angiogenesis, which permits delivery of oxygen carrying blood to hypoxic sites; glycolysis, as a means of energy production; xenobiotic detoxification; and cellular adaptation to stress. Hypoxia-inducible proteins within these respective categories include erythropoietin (EPO) 1 (5), vascular endothelial growth factor (6), glycolytic enzymes (7-9), NAD(P)H:quinone oxidoreductase (10), and heat shock proteins (11,12). Where examined, increased expression of specific proteins in response to hypoxia is regulated primarily at the level of gene transcription (although posttranscriptional mechanisms have also been characterized).Another stress-associated protein whose expression is stimulated by hypoxia is heme oxygenase-1 (HO-1) (13, 14). HO-1, a microsomal membrane enzyme, catalyzes the first and ratelimiting reaction in heme catabolism, the oxidative cleavage of b-type heme molecules to yield equimolar quantities of biliverdin, carbon monoxide (CO), and iron. Biliverdin is subsequently converted to bilirubin by the action of biliverdin reductase. The expression of HO-1 is dramatically induced not only by the substrate, heme, but a variety of stress-associated agents, including heavy metals, hyperthermia, and UV irradiation (reviewed in Maines (15)). A common feature among these inducers, including heme, is that they generate reactive oxygen species and/or diminish glutathione levels. This correlation and the observation that bilirubin functions as an antioxidant (16) has led to the hypothesis that induction of HO-1 is part of a general response to oxidant stress and that this enzyme plays a protective role during such conditions (17)(18)(19).Stimulation of HO-1 expression by most if not all inducers is controlled primarily at the level of gene transcription and in our studies on the regulation of the mouse HO-1 gene, we have identified two 5Ј distal enhancer regions, SX2 and AB1, that mediate gene activation by a variety of pro-oxidants including heme, heavy metals, TPA, hydrogen peroxide, and LPS (20 -23). The mechanism of HO-1 induction by hypoxia has not been investigated and because this induction has been proposed to occur as a consequence of oxidative stress (13), we examined the role of the SX2 and AB1 enhancers in hypoxia-dependent gene activation. In this report we show that these enhancers do not mediate transcriptional activation of the HO-1 gene in response to hypoxia. Rather, this induction is mediated by a 163-bp fragment located directly downstream of ...

Fibrosis and apoptosis are juxtaposed in pulmonary disorders such as asthma and the interstitial diseases, and transforming growth factor (TGF)-β1 has been implicated in the pathogenesis of these responses. However, the in vivo effector functions of TGF-β1 in the lung and its roles in the pathogenesis of these responses are not completely understood. In addition, the relationships between apoptosis and other TGF-β1–induced responses have not been defined. To address these issues, we targeted bioactive TGF-β1 to the murine lung using a novel externally regulatable, triple transgenic system. TGF-β1 produced a transient wave of epithelial apoptosis that was followed by mononuclear-rich inflammation, tissue fibrosis, myofibroblast and myocyte hyperplasia, and septal rupture with honeycombing. Studies of these mice highlighted the reversibility of this fibrotic response. They also demonstrated that a null mutation of early growth response gene (Egr)-1 or caspase inhibition blocked TGF-β1–induced apoptosis. Interestingly, both interventions markedly ameliorated TGF-β1–induced fibrosis and alveolar remodeling. These studies illustrate the complex effects of TGF-β1 in vivo and define the critical role of Egr-1 in the TGF-β1 phenotype. They also demonstrate that Egr-1–mediated apoptosis is a prerequisite for TGF-β1–induced fibrosis and remodeling.

Coronavirus infection causes diffuse alveolar damage leading to acute respiratory distress syndrome. The absence of ex vivo models of human alveolar epithelium is hindering an understanding of COVID-19 pathogenesis. We report a feeder-free, scalable, chemically-defined, and modular alveolosphere culture system for propagation and differentiation of human alveolar type 2 cells/pneumocytes derived from primary lung tissue. Cultured pneumocytes express the SARS-CoV-2 receptor ACE2 and can be infected with virus. Transcriptome and histological analysis of infected alveolospheres mirrors features of COVID-19 lungs, including emergence of interferon mediated inflammatory responses, loss of surfactant proteins, and apoptosis. Treatment of alveolospheres with interferons recapitulates features of virus infection, including cell death. In contrast, alveolospheres pretreated with low dose IFNs show a reduction in viral replication, suggesting the prophylactic effectiveness of IFNs against SARS-CoV-2. Human stem cell-based alveolospheres thus provide novel insights into COVID-19 pathogenesis and can serve as a model for understanding human respiratory diseases.