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Irritability is increasingly recognized as a significant clinical problem in youth. It is a criterion for multiple diagnoses and predicts the development of a wide range of disorders. Research on etiopathogenesis suggests that genetic and family environmental factors play a role, as do abnormalities in reward and cognitive control circuitry. However, many of these effects are age dependent. Threat-responsive self-regulatory systems and the degree to which irritability manifests as tonic or phasic influence whether irritable youth exhibit more internalizing versus externalizing outcomes.Vaccine hesitancy and emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) escaping vaccine-induced immune responses highlight the urgency for new COVID-19 therapeutics. Engineered angiotensin-converting enzyme 2 (ACE2) proteins with augmented binding affinities for SARS-CoV-2 spike (S) protein may prove to be especially efficacious against multiple variants. Using molecular dynamics simulations and functional assays, we show that three amino acid substitutions in an engineered soluble ACE2 protein markedly augmented the affinity for the S protein of the SARS-CoV-2 WA-1/2020 isolate and multiple VOCs B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma) and B.1.617.2 (Delta). In humanized K18-hACE2 mice infected with the SARS-CoV-2 WA-1/2020 or P.1 variant, prophylactic and therapeutic injections of soluble ACE22.v2.4-IgG1 prevented lung vascular injury and edema formation, essential features of CoV-2-induced SARS, and above all improved survival. These studies demonstrate broad efficacy in vivo of an engineered ACE2 decoy against SARS-CoV-2 variants in mice and point to its therapeutic potential.Nitrogen dioxide (NO2) is an important contributor to air pollution and can adversely affect human health1-9. A decrease in NO2 concentrations has been reported as a result of lockdown measures to reduce the spread of COVID-1910-20. Questions remain, however, regarding the relationship of satellite-derived atmospheric column NO2 data with health-relevant ambient ground-level concentrations, and the representativeness of limited ground-based monitoring data for global assessment. Here we derive spatially resolved, global ground-level NO2 concentrations from NO2 column densities observed by the TROPOMI satellite instrument at sufficiently fine resolution (approximately one kilometre) to allow assessment of individual cities during COVID-19 lockdowns in 2020 compared to 2019. We apply these estimates to quantify NO2 changes in more than 200 cities, including 65 cities without available ground monitoring, largely in lower-income regions. Mean country-level population-weighted NO2 concentrations are 29% ± 3% lower in countries with strict lockdown conditions than in those without. Relative to long-term trends, NO2 decreases during COVID-19 lockdowns exceed recent Ozone Monitoring Instrument (OMI)-derived year-to-year decreases from emission controls, comparable to 15 ± 4 years of reductions globally. Our case studies indicate that the sensitivity of NO2 to lockdowns varies by country and emissions sector, demonstrating the critical need for spatially resolved observational information provided by these satellite-derived surface concentration estimates.Chirality is a unifying structural metric of biological and abiological forms of matter. Over the past decade, considerable clarity has been achieved in understanding the chemistry and physics of chiral inorganic nanoparticles1-4; however, little is known about their effects on complex biochemical networks5,6. Intermolecular interactions of biological molecules and inorganic nanoparticles show some commonalities7-9, but these structures differ in scale, in geometry and in the dynamics of chiral shapes, which can both impede and strengthen their mirror-asymmetric complexes. Here we show that achiral and left- and right-handed gold biomimetic nanoparticles show different in vitro and in vivo immune responses. We use irradiation with circularly polarized light (CPL) to synthesize nanoparticles with controllable nanometre-scale chirality and optical anisotropy factors (g-factors) of up to 0.4. We find that binding of nanoparticles to two proteins from the family of adhesion G-protein-coupled receptors (AGPCRs)-namely cluster-of-differentiation 97 (CD97) and epidermal-growth-factor-like-module receptor 1 (EMR1)-results in the opening of mechanosensitive potassium-efflux channels, the production of immune signalling complexes known as inflammasomes, and the maturation of mouse bone-marrow-derived dendritic cells. Both in vivo and in vitro immune responses depend monotonically on the g-factors of the nanoparticles, indicating that nanoscale chirality can be used to regulate the maturation of immune cells. Finally, left-handed nanoparticles show substantially higher (1,258-fold) efficiency compared with their right-handed counterparts as adjuvants for vaccination against the H9N2 influenza virus, opening a path to the use of nanoscale chirality in immunology.The melting of glaciers and ice caps accounts for about one-third of current sea-level rise1-3, exceeding the mass loss from the more voluminous Greenland or Antarctic Ice Sheets3,4. The Arctic archipelago of Svalbard, which hosts spatial climate gradients that are larger than the expected temporal climate shifts over the next century5,6, is a natural laboratory to constrain the climate sensitivity of glaciers and predict their response to future warming. Here we link historical and modern glacier observations to predict that twenty-first century glacier thinning rates will more than double those from 1936 to 2010. Making use of an archive of historical aerial imagery7 from 1936 and 1938, we use structure-from-motion photogrammetry to reconstruct the three-dimensional geometry of 1,594 glaciers across Svalbard. We compare these reconstructions to modern ice elevation data to derive the spatial pattern of mass balance over a more than 70-year timespan, enabling us to see through the noise of annual and decadal variability to quantify how variables such as temperature and precipitation control ice loss. We find a robust temperature dependence of melt rates, whereby a 1 °C rise in mean summer temperature corresponds to a decrease in area-normalized mass balance of -0.28 m yr-1 of water equivalent. Finally, we design a space-for-time substitution8 to combine our historical glacier observations with climate projections and make first-order predictions of twenty-first century glacier change across Svalbard.High-fidelity control of quantum bits is paramount for the reliable execution of quantum algorithms and for achieving fault tolerance-the ability to correct errors faster than they occur1. The central requirement for fault tolerance is expressed in terms of an error threshold. Whereas the actual threshold depends on many details, a common target is the approximately 1% error threshold of the well-known surface code2,3. Reaching two-qubit gate fidelities above 99% has been a long-standing major goal for semiconductor spin qubits. These qubits are promising for scaling, as they can leverage advanced semiconductor technology4. Here we report a spin-based quantum processor in silicon with single-qubit and two-qubit gate fidelities, all of which are above 99.5%, extracted from gate-set tomography. The average single-qubit gate fidelities remain above 99% when including crosstalk and idling errors on the neighbouring qubit. Using this high-fidelity gate set, we execute the demanding task of calculating molecular ground-state energies using a variational quantum eigensolver algorithm5. Having surpassed the 99% barrier for the two-qubit gate fidelity, semiconductor qubits are well positioned on the path to fault tolerance and to possible applications in the era of noisy intermediate-scale quantum devices.Fault-tolerant quantum computers that can solve hard problems rely on quantum error correction1. One of the most promising error correction codes is the surface code2, which requires universal gate fidelities exceeding an error correction threshold of 99 per cent3. Among the many qubit platforms, only superconducting circuits4, trapped ions5 and nitrogen-vacancy centres in diamond6 have delivered this requirement. Electron spin qubits in silicon7-15 are particularly promising for a large-scale quantum computer owing to their nanofabrication capability, but the two-qubit gate fidelity has been limited to 98 per cent owing to the slow operation16. Here we demonstrate a two-qubit gate fidelity of 99.5 per cent, along with single-qubit gate fidelities of 99.8 per cent, in silicon spin qubits by fast electrical control using a micromagnet-induced gradient field and a tunable two-qubit coupling. We identify the qubit rotation speed and coupling strength where we robustly achieve high-fidelity gates. We realize Deutsch-Jozsa and Grover search algorithms with high success rates using our universal gate set. Our results demonstrate universal gate fidelity beyond the fault-tolerance threshold and may enable scalable silicon quantum computers.Phase transitions connect different states of matter and are often concomitant with the spontaneous breaking of symmetries. An important category of phase transitions is mobility transitions, among which is the well known Anderson localization1, where increasing the randomness induces a metal-insulator transition. The introduction of topology in condensed-matter physics2-4 lead to the discovery of topological phase transitions and materials as topological insulators5. Phase transitions in the symmetry of non-Hermitian systems describe the transition to on-average conserved energy6 and new topological phases7-9. Bulk conductivity, topology and non-Hermitian symmetry breaking seemingly emerge from different physics and, thus, may appear as separable phenomena. However, in non-Hermitian quasicrystals, such transitions can be mutually interlinked by forming a triple phase transition10. Here we report the experimental observation of a triple phase transition, where changing a single parameter simultaneously gives rise to a localization (metal-insulator), a topological and parity-time symmetry-breaking (energy) phase transition. The physics is manifested in a temporally driven (Floquet) dissipative quasicrystal. We implement our ideas via photonic quantum walks in coupled optical fibre loops11. Our study highlights the intertwinement of topology, symmetry breaking and mobility phase transitions in non-Hermitian quasicrystalline synthetic matter. Our results may be applied in phase-change devices, in which the bulk and edge transport and the energy or particle exchange with the environment can be predicted and controlled.Nuclear spins were among the first physical platforms to be considered for quantum information processing1,2, because of their exceptional quantum coherence3 and atomic-scale footprint. However, their full potential for quantum computing has not yet been realized, owing to the lack of methods with which to link nuclear qubits within a scalable device combined with multi-qubit operations with sufficient fidelity to sustain fault-tolerant quantum computation. ODM208 order Here we demonstrate universal quantum logic operations using a pair of ion-implanted 31P donor nuclei in a silicon nanoelectronic device. A nuclear two-qubit controlled-Z gate is obtained by imparting a geometric phase to a shared electron spin4, and used to prepare entangled Bell states with fidelities up to 94.2(2.7)%. The quantum operations are precisely characterized using gate set tomography (GST)5, yielding one-qubit average gate fidelities up to 99.95(2)%, two-qubit average gate fidelity of 99.37(11)% and two-qubit preparation/measurement fidelities of 98.

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