Indistinguishable telecom band photons from a single Er ion in the solid state.

Atomic defects in the solid state are a key component of quantum repeater networks for long-distance quantum communication1. Recently, there has been significant interest in rare earth ions2-4, in particular Er3+ for its telecom band optical transition5-7 that allows long-distance transmission in optical fibres. However, the development of repeater nodes based on rare earth ions has been hampered by optical spectral diffusion, precluding indistinguishable single-photon generation. Here, we implant Er3+ into CaWO4, a material that combines a non-polar site symmetry, low decoherence from nuclear spins8 and is free of background rare earth ions, to realize significantly reduced optical spectral diffusion. For shallow implanted ions coupled to nanophotonic cavities with large Purcell factor, we observe single-scan optical linewidths of 150 kHz and long-term spectral diffusion of 63 kHz, both close to the Purcell-enhanced radiative linewidth of 21 kHz. This enables the observation of Hong-Ou-Mandel interference9 between successively emitted photons with a visibility of V = 80(4)%, measured after a 36 km delay line. We also observe spin relaxation times T1,s = 3.7 s and T2,s > 200 µs, with the latter limited by paramagnetic impurities in the crystal instead of nuclear spins. This represents a notable step towards the construction of telecom band quantum repeater networks with single Er3+ ions.

High-fidelity gates and mid-circuit erasure conversion in an atomic qubit.

The development of scalable, high-fidelity qubits is a key challenge in quantum information science. Neutral atom qubits have progressed rapidly in recent years, demonstrating programmable processors1,2 and quantum simulators with scaling to hundreds of atoms3,4. Exploring new atomic species, such as alkaline earth atoms5-7, or combining multiple species8 can provide new paths to improving coherence, control and scalability. For example, for eventual application in quantum error correction, it is advantageous to realize qubits with structured error models, such as biased Pauli errors9 or conversion of errors into detectable erasures10. Here we demonstrate a new neutral atom qubit using the nuclear spin of a long-lived metastable state in 171Yb. The long coherence time and fast excitation to the Rydberg state allow one- and two-qubit gates with fidelities of 0.9990(1) and 0.980(1), respectively. Importantly, a large fraction of all gate errors result in decays out of the qubit subspace to the ground state. By performing fast, mid-circuit detection of these errors, we convert them into erasure errors; during detection, the induced error probability on qubits remaining in the computational space is less than 10-5. This work establishes metastable 171Yb as a promising platform for realizing fault-tolerant quantum computing.

A phase 2 study of AZD4635 in combination with durvalumab or oleclumab in patients with metastatic castration-resistant prostate cancer.

BACKGROUND: Inhibition of the adenosine 2A receptor (A2AR) diminishes the immunosuppressive effects of adenosine and may complement immune-targeting drugs. This phase 2 study evaluated the A2AR antagonist AZD4635 in combination with durvalumab or oleclumab in patients with metastatic castration-resistant prostate cancer. METHODS: Patients with histologically/cytologically confirmed disease progressing within 6 months on ≥ 2 therapy lines were randomly assigned to either Module 1 (AZD4635 + durvalumab) or Module 2 (AZD4635 + oleclumab). Primary endpoints were objective response rate per RECIST v1.1 and prostate-specific antigen (PSA) response rate. Secondary endpoints included radiological progression-free survival (rPFS), overall survival, safety, and pharmacokinetics. RESULTS: Fifty-nine patients were treated (Module 1, n = 29; Module 2, n = 30). Median number of prior therapies was 4. One confirmed complete response by RECIST (Module 1) and 2 confirmed PSA responses (1 per module) were observed. The most frequent adverse events (AEs) possibly related to AZD4635 were nausea (37.9%), fatigue (20.7%), and decreased appetite (17.2%) in Module 1; nausea (50%), fatigue (30%), and vomiting (23.3%) in Module 2. No dose-limiting toxicities or treatment-related serious AEs were observed. In Module 1, AZD4635 geometric mean trough concentration was 124.9 ng/mL (geometric CV% 69.84; n = 22); exposures were similar in Module 2. In Modules 1 and 2, median (95% CI) rPFS was 2.3 (1.6 -3.8) and 1.5 (1.3- 4.0) months, respectively. Median PFS was 1.7 versus 2.3 months for patients with high versus low blood-based adenosine signature. CONCLUSION: In this heavily pretreated population, AZD4635 with durvalumab or oleclumab demonstrated minimal antitumor activity with a manageable safety profile. CLINICAL TRIAL: gov identifier: NCT04089553.

Erbium-Excess Gallium Garnets.

A series of garnets of formula Er3+xGa5-xO12 are described, for which we report the crystal structures for both polycrystalline and single-crystal samples. The x limit in the garnet phase is between 0.5 and 0.6 under our conditions, with the Er fully occupying the dodecahedral (24c) garnet site plus some of the octahedral site (16a) in place of the Ga normally present. Long-range antiferromagnetic order with spin-ice-like frustration is suggested by the transition temperature (TN ≈ 0.8 K) being lower than the Curie-Weiss theta. The magnetic ordering temperature does not depend on the Er excess, but there is increasing residual entropy as the Er excess is increased, highlighting the potential for unusual magnetic behavior in this system. The field-dependent magnetic entropy trend is consistent with the reported behavior for frustrated triangular magnetic systems: an increasing transition temperature with a broader hump as the applied field increases [Xing, J.; Phys. Rev. Mater. 2019, 3(11), 114413;Filippi, J.; Solid State Commun. 1977, 23(9), 613-616; Bloxsom, J. A. Thermal and Magnetic Studies of Spin Ice Compounds. University College London, 2016].

Symmetry-protected collisions between strongly interacting photons.

Realizing robust quantum phenomena in strongly interacting systems is one of the central challenges in modern physical science. Approaches ranging from topological protection to quantum error correction are currently being explored across many different experimental platforms, including electrons in condensed-matter systems, trapped atoms and photons. Although photon-photon interactions are typically negligible in conventional optical media, strong interactions between individual photons have recently been engineered in several systems. Here, using coherent coupling between light and Rydberg excitations in an ultracold atomic gas, we demonstrate a controlled and coherent exchange collision between two photons that is accompanied by a π/2 phase shift. The effect is robust in that the value of the phase shift is determined by the interaction symmetry rather than the precise experimental parameters, and in that it occurs under conditions where photon absorption is minimal. The measured phase shift of 0.48(3)π is in excellent agreement with a theoretical model. These observations open a route to realizing robust single-photon switches and all-optical quantum logic gates, and to exploring novel quantum many-body phenomena with strongly interacting photons.

Mechanistic Insights into Passive Membrane Permeability of Drug-like Molecules from a Weighted Ensemble of Trajectories.

Passive permeability of a drug-like molecule is a critical property assayed early in a drug discovery campaign that informs a medicinal chemist how well a compound can traverse biological membranes, such as gastrointestinal epithelial or restrictive organ barriers, so it can perform a specific therapeutic function. However, the challenge that remains is the development of a method, experimental or computational, which can both determine the permeation rate and provide mechanistic insights into the transport process to help with the rational design of any given molecule. Typically, one of the following three methods are used to measure the membrane permeability: (1) experimental permeation assays acting on either artificial or natural membranes; (2) quantitative structure-permeability relationship models that rely on experimental values of permeability or related pharmacokinetic properties of a range of molecules to infer those for new molecules; and (3) estimation of permeability from the Smoluchowski equation, where free energy and diffusion profiles along the membrane normal are taken as input from large-scale molecular dynamics simulations. While all these methods provide estimates of permeation coefficients, they provide very little information for guiding rational drug design. In this study, we employ a highly parallelizable weighted ensemble (WE) path sampling strategy, empowered by cloud computing techniques, to generate unbiased permeation pathways and permeability coefficients for a set of drug-like molecules across a neat 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine membrane bilayer. Our WE method predicts permeability coefficients that compare well to experimental values from an MDCK-LE cell line and PAMPA assays for a set of drug-like amines of varying size, shape, and flexibility. Our method also yields a series of continuous permeation pathways weighted and ranked by their associated probabilities. Taken together, the ensemble of reactive permeation pathways, along with the estimate of the permeability coefficient, provides a clearer picture of the microscopic underpinnings of small-molecule membrane permeation.

Hybrid III-V diamond photonic platform for quantum nodes based on neutral silicon vacancy centers in diamond.

Integrating atomic quantum memories based on color centers in diamond with on-chip photonic devices would enable entanglement distribution over long distances. However, efforts towards integration have been challenging because color centers can be highly sensitive to their environment, and their properties degrade in nanofabricated structures. Here, we describe a heterogeneously integrated, on-chip, III-V diamond platform designed for neutral silicon vacancy (SiV0) centers in diamond that circumvents the need for etching the diamond substrate. Through evanescent coupling to SiV0 centers near the surface of diamond, the platform will enable Purcell enhancement of SiV0 emission and efficient frequency conversion to the telecommunication C-band. The proposed structures can be realized with readily available fabrication techniques.

Hybrid microwave-optical scanning probe for addressing solid-state spins in nanophotonic cavities.

Spin-photon interfaces based on solid-state atomic defects have enabled a variety of key applications in quantum information processing. To maximize the light-matter coupling strength, defects are often placed inside nanoscale devices. Efficiently coupling light and microwave radiation into these structures is an experimental challenge, especially in cryogenic or high vacuum environments with limited sample access. In this work, we demonstrate a fiber-based scanning probe that simultaneously couples light into a planar photonic circuit and delivers high power microwaves for driving electron spin transitions. The optical portion achieves 46% one-way coupling efficiency, while the microwave portion supplies an AC magnetic field with strength up to 9 Gauss at 10 Watts of input microwave power. The entire probe can be scanned across a large number of devices inside a 3He cryostat without free-space optical access. We demonstrate this technique with silicon nanophotonic circuits coupled to single Er3+ ions.

Narrow Optical Line Widths in Erbium Implanted in TiO2.

Atomic and atomlike defects in the solid state are widely explored for quantum computers, networks, and sensors. Rare earth ions are an attractive class of atomic defects that feature narrow spin and optical transitions that are isolated from the host crystal, allowing incorporation into a wide range of materials. However, the realization of long electronic spin coherence times is hampered by magnetic noise from abundant nuclear spins in the most widely studied host crystals. Here, we demonstrate that Er3+ ions can be introduced via ion implantation into TiO2, a host crystal that has not been studied extensively for rare earth ions and has a low natural abundance of nuclear spins. We observe efficient incorporation of the implanted Er3+ into the Ti4+ site (>50% yield) and measure narrow inhomogeneous spin and optical line widths (20 and 460 MHz, respectively) that are comparable to bulk-doped crystalline hosts for Er3+. This work demonstrates that ion implantation is a viable path to studying rare earth ions in new hosts and is a significant step toward realizing individually addressed rare earth ions with long spin coherence times for quantum technologies.

System-size effects in ionic fluids under periodic boundary conditions.

We investigate the system-size dependence of the thermodynamic properties of ionic fluids under periodic boundary conditions. Following an approach previously developed in the context of quantum Monte Carlo simulations of many-electron systems, we show that the leading-order finite-size artifact in the Coulomb energy per particle of a classical fluid of N structureless ions at given density and temperature is simply -kBT(2N)-1. Analytical approximations for the periodicity-induced size dependence of the excess thermodynamic properties of the fluid in the weak-coupling regime are obtained within the linearized Debye-Hückel theory. Theoretical results are compared with published simulations of the one-component plasma and our own simulations of a primitive-model electrolyte solution. Our work is directly relevant to estimating finite-size corrections in simulations of charged fluids comprising structureless ions embedded in continuous media. We outline in the Appendix how some of our formal results may be generalized to molecular fluids with mobile ions; e.g., electrolyte solutions with explicit solvent.

EXPANDING EVIDENCE-BASED TECHNOLOGY ASSESSMENT FOR COVERAGE IN WASHINGTON STATE.

OBJECTIVES: We describe a new evidence-based method for screening and evaluating emerging medical technologies. Washington State agencies, under legislative direction, have granted authority to its agency Medical Directors and policy leaders to make coverage decisions on medical technologies using a "dossier" process. The dossier process is employed when technology advocates or manufacturers request Washington State healthcare purchasers to pay for new and emerging technologies. This offers the advocate an opportunity to submit scientific evidence and information classically associated with a more formal health technology assessment. METHODS: The submitted information is independently reviewed and summarized for Washington State's public healthcare purchasers allowing a more standardized coverage decision for all public purchasers in Washington State. RESULTS: This process has allowed Washington State to make twelve evidence-based coverage decisions at a fraction of the cost of classic technology assessment. To date, of twelve reviews over 6 years, one health technology was approved for coverage, ten were not covered and one did not require a coverage decision. CONCLUSIONS: This evidence-based dossier process has yielded high-value coverage decisions of new and emerging medical technologies for public healthcare purchasers in Washington State.

NASA resilience and leadership: examining the phenomenon of awe.

This study examines how a phenomenon, awe, along with related resilience practices, is perceived by a NASA medical and mental health professional, who also serves in a leadership role, and how awe has impacted their work and personal life. Considering both their leadership role and how their work involves supporting the wellbeing of astronauts pre-mission, during missions, and post-mission, the potential impact of awe on the NASA expert has individual implications along with many others, especially in stressful environments. The results indicate that reflecting on awe experiences can support a person finding meaning and purpose in their life, evoke gratitude, increase social connectedness, promote optimism and other resilience skills in the moment, and generally have a sustainable positive effect.

Hostage negotiator resilience: A phenomenological study of awe.

Law enforcement crisis and hostage negotiators (CHNs) are tasked with resolving incidents that are stressful, unpredictable, and often dangerous. These negotiators must work as a team and be able to successfully utilize a variety of skills in order to gain the subject's voluntary compliance and peaceful surrender. It is necessary for negotiators to continually practice these skills while also, and importantly, care for their own wellbeing. This study examines how a phenomenon, awe, when viewed as a resilience practice, can support law enforcement crisis hostage negotiators with their crisis work and personal wellness. Utilizing phenomenological methodologies, the findings demonstrate that reflecting on awe experiences had an overall positive impact on the negotiators in both their professional and personal lives. Based on the results, it is suggested that awe practices could be incorporated into future negotiator trainings in order to increase resilience and assist negotiators personally and professionally.

Clinical and imaging modality factors impacting radiological interpretation of breast screening in young women with neurofibromatosis type 1.

Young women with Neurofibromatosis type 1 (NF1) have a high risk of developing breast cancer and poorer survival following breast cancer diagnosis. International guidelines recommend commencing breast screening between 30 and 35 years; however, the optimal screening modality is unestablished, and previous reports suggest that breast imaging may be complicated by the presence of intramammary and cutaneous neurofibromas (cNFs). The aim of this study was to explore potential barriers to implementation of breast screening for young women with NF1.Twenty-seven women (30-47 years) with NF1 completed breast screening with breast MRI, mammogram and breast ultrasound. Nineteen probably benign/suspicious lesions were detected across 14 women. Despite the presence of breast cNFs, initial biopsy rate for participants with NF1 (37%), were comparable to a BRCA pathogenic variant (PV) cohort (25%) (P = 0.311). No cancers or intramammary neurofibromas were identified. Most participants (89%) returned for second round screening.The presence of cNF did not affect clinician confidence in 3D mammogram interpretation, although increasing breast density, frequently seen in young women, impeded confidence for 2D and 3D mammogram. Moderate or marked background parenchymal enhancement on MRI was higher in the NF1 cohort (70.4%) than BRCA PV carriers (47.3%), which is an independent risk factor for breast cancer.Breast MRI was the preferred mode of screening over mammogram, as the majority (85%) with NF1 demonstrated breast density (BI-RADS 3C/4D), which hinders mammogram interpretation. For those with high breast density and high cNF breast coverage, 3D rather than 2D mammogram is preferred, if MRI is unavailable.

A Suite of Tutorials for the WESTPA 2.0 Rare-Events Sampling Software [Article v2.0].

The weighted ensemble (WE) strategy has been demonstrated to be highly efficient in generating pathways and rate constants for rare events such as protein folding and protein binding using atomistic molecular dynamics simulations. Here we present two sets of tutorials instructing users in the best practices for preparing, carrying out, and analyzing WE simulations for various applications using the WESTPA software. The first set of more basic tutorials describes a range of simulation types, from a molecular association process in explicit solvent to more complex processes such as host-guest association, peptide conformational sampling, and protein folding. The second set ecompasses six advanced tutorials instructing users in the best practices of using key new features and plugins/extensions of the WESTPA 2.0 software package, which consists of major upgrades for larger systems and/or slower processes. The advanced tutorials demonstrate the use of the following key features: (i) a generalized resampler module for the creation of "binless" schemes, (ii) a minimal adaptive binning scheme for more efficient surmounting of free energy barriers, (iii) streamlined handling of large simulation datasets using an HDF5 framework, (iv) two different schemes for more efficient rate-constant estimation, (v) a Python API for simplified analysis of WE simulations, and (vi) plugins/extensions for Markovian Weighted Ensemble Milestoning and WE rule-based modeling for systems biology models. Applications of the advanced tutorials include atomistic and non-spatial models, and consist of complex processes such as protein folding and the membrane permeability of a drug-like molecule. Users are expected to already have significant experience with running conventional molecular dynamics or systems biology simulations.

Awe Narratives: A Mindfulness Practice to Enhance Resilience and Wellbeing.

It is necessary to have available a variety of evidence-based resilience practices as we experience life's stressors including the ongoing COVID-19 pandemic. Evoking, experiencing, and reflecting on awe moments by developing and sharing an "awe narrative" are a type of mindfulness technique that can have the potential to help someone flourish, enhance their resilience, and have a positive impact on their overall wellbeing. This paper explores how constructing an awe narrative can assist the individual while also possibly having a positive impact on others.

Erasure conversion for fault-tolerant quantum computing in alkaline earth Rydberg atom arrays.

Executing quantum algorithms on error-corrected logical qubits is a critical step for scalable quantum computing, but the requisite numbers of qubits and physical error rates are demanding for current experimental hardware. Recently, the development of error correcting codes tailored to particular physical noise models has helped relax these requirements. In this work, we propose a qubit encoding and gate protocol for 171Yb neutral atom qubits that converts the dominant physical errors into erasures, that is, errors in known locations. The key idea is to encode qubits in a metastable electronic level, such that gate errors predominantly result in transitions to disjoint subspaces whose populations can be continuously monitored via fluorescence. We estimate that 98% of errors can be converted into erasures. We quantify the benefit of this approach via circuit-level simulations of the surface code, finding a threshold increase from 0.937% to 4.15%. We also observe a larger code distance near the threshold, leading to a faster decrease in the logical error rate for the same number of physical qubits, which is important for near-term implementations. Erasure conversion should benefit any error correcting code, and may also be applied to design new gates and encodings in other qubit platforms.

WESTPA 2.0: High-Performance Upgrades for Weighted Ensemble Simulations and Analysis of Longer-Timescale Applications.

The weighted ensemble (WE) family of methods is one of several statistical mechanics-based path sampling strategies that can provide estimates of key observables (rate constants and pathways) using a fraction of the time required by direct simulation methods such as molecular dynamics or discrete-state stochastic algorithms. WE methods oversee numerous parallel trajectories using intermittent overhead operations at fixed time intervals, enabling facile interoperability with any dynamics engine. Here, we report on the major upgrades to the WESTPA software package, an open-source, high-performance framework that implements both basic and recently developed WE methods. These upgrades offer substantial improvements over traditional WE methods. The key features of the new WESTPA 2.0 software enhance the efficiency and ease of use: an adaptive binning scheme for more efficient surmounting of large free energy barriers, streamlined handling of large simulation data sets, exponentially improved analysis of kinetics, and developer-friendly tools for creating new WE methods, including a Python API and resampler module for implementing both binned and "binless" WE strategies.

Impact of food restriction and cocaine on locomotion in ghrelin- and ghrelin-receptor knockout mice.

Food restriction (FR) augments the behavioral and reinforcing effects of psychomotor stimulants such as cocaine or amphetamine; effects that may be related to the capacity of FR to increase plasma levels of ghrelin (GHR), a 28-amino acid orexigenenic peptide linked to activation of brain dopamine systems. The present study used wild-type (WT) mice or mutant mice sustaining knockout of either GHR [GHR((-/-)) ] or of the growth hormone secretagogue receptor [GHS-R((-/-)) ] and subjected to FR or not to evaluate the role of GHR and GHS-R in cocaine-stimulated locomotion. WT, GHR((-/-)) , and GHS-R((-/-)) mice were either restricted to 60% of baseline caloric intake or allowed to free-feed (FF). Mice were treated with 0, 1.25, 2.5 and 5.0 mg/kg cocaine on separate test days (in random dose order) and forward locomotion was recorded on each drug day for 45 minutes after drug dosing. Food (and water) was available immediately after (but not during) each activity test. For FF mice, there was no interaction between cocaine and GHR status on locomotion. FR-WT mice treated with saline exhibited significant increases in anticipatory locomotion (relative to FF-WT mice), whereas FR-GHS-R((-/-)) mice did not. Cocaine significantly increased locomotion in FR-GHR((-/-)) and FR-GHS-R((-/-)) mice to the levels noted in FR-WT mice. These results suggest that GHS-R activity, but not GHR activity, is required for FR to augment food-associated anticipatory locomotion, but do not support the contention that GHR pathways are required for the capacity of FR to augment the acute effect of cocaine on locomotion.