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We report the p+p and p+d differential cross sections measured in the SeaQuest experiment for J/ψ and ψ(2S) production at [Formula presented] beam energy covering the forward x-Feynman (xF) range of 0.5

To facilitate our understanding of proteome dynamics during signaling events, robust workflows affording fast time resolution without confounding factors are essential. We present Surface-exposed protein Labeling using PeroxidaSe, H2O2, and Tyramide-derivative (SLAPSHOT) to label extracellularly exposed proteins in a rapid, specific, and sensitive manner. Simple and flexible SLAPSHOT utilizes recombinant soluble APEX2 protein applied to cells, thus circumventing the engineering of tools and cells, biological perturbations, and labeling biases. We applied SLAPSHOT and quantitative proteomics to examine the TMEM16F-dependent plasma membrane remodeling in WT and TMEM16F KO cells. Time-course data ranging from 1 to 30 min of calcium stimulation revealed co-regulation of known protein families, including the integrin and ICAM families, and identified proteins known to reside in intracellular organelles as occupants of the freshly deposited extracellularly exposed membrane. Our data provide the first accounts of the immediate consequences of calcium signaling on the extracellularly exposed proteome.

Abstract: In 2010, Bakos and collaborators discovered a Neptune-sized planet transiting the K-dwarf HAT-P-11 every five days. Later in 2018, Yee and collaborators reported an additional Jovian-mass companion on a nine year orbit based on a decade of Doppler monitoring. The eccentric outer giant HAT-P-11c may be responsible for the peculiar polar orbit of the inner planet HAT-P-11b. However, Basilicata et al. recently suggested that the HAT-P-11c Doppler signal could be caused by stellar activity. In this research note, we extend the Yee et al. Doppler time series by six years. The combined data set spanning 17 yr covers nearly two orbits of the outer planet. Importantly, we observe two periastron passages of planet c and do not observe a coherent activity signature. Together with the previously reported astrometric acceleration of HAT-P-11 from Hipparcos and Gaia, we believe there is strong evidence for HAT-P-11c as a bona fide planet.

Multiomics has shown promise in noninvasive risk profiling and early detection of various common diseases. In the present study, in a prospective population-based cohort with ~18 years of e-health record follow-up, we investigated the incremental and combined value of genomic and gut metagenomic risk assessment compared with conventional risk factors for predicting incident coronary artery disease (CAD), type 2 diabetes (T2D), Alzheimer disease and prostate cancer. We found that polygenic risk scores (PRSs) improved prediction over conventional risk factors for all diseases. Gut microbiome scores improved predictive capacity over baseline age for CAD, T2D and prostate cancer. Integrated risk models of PRSs, gut microbiome scores and conventional risk factors achieved the highest predictive performance for all diseases studied compared with models based on conventional risk factors alone. The present study demonstrates that integrated PRSs and gut metagenomic risk models improve the predictive value over conventional risk factors for common chronic diseases.

Discovering and characterizing exoplanets at the outer edge of the transit method’s sensitivity has proven challenging owing to geometric biases and the practical difficulties associated with acquiring long observational baselines. Nonetheless, a sample of giant exoplanets on orbits longer than 100 days has been identified by transit hunting missions. We present long-term Doppler spectroscopy for 11 such systems with observation baselines spanning a few years to a decade. We model these radial velocity observations jointly with transit photometry to provide initial characterizations of these objects and the systems in which they exist. Specifically, we make new precise mass measurements for four long-period giant exoplanets (Kepler-111 c, Kepler-553 c, Kepler-849 b, and PH-2 b), we place new upper limits on mass for four others (Kepler-421 b, KOI-1431.01, Kepler-1513 b, and Kepler-952 b), and we show that several confirmed planets are in fact not planetary at all. We present these findings to complement similar efforts focused on closer-in short-period giant planets, and with the hope of inspiring future dedicated studies of cool giant exoplanets.

This study evaluated 10-year secular changes in dental maturity and dental development among Korean children. A retrospective analysis of panoramic radiograph samples from Korean children (4–16 years old) taken in 2010 and 2020 was conducted. The 2010 group consisted of 3491 radiographs (1970 boys and 1521 girls), and the 2020 group included 5133 radiographs (2825 boys and 2308 girls). Using Demirjian’s method, dental maturity scores and dental developmental stages were assessed. For intra-observer reliability, Weighted Cohen’s kappa was used, and Mann-Whitney U tests were performed to compare the 2020 and 2010 groups. A slight acceleration in dental maturity was observed in both boys and girls, with the difference being more noticeable in boys at an earlier age. Statistically significant differences were noted at ages 4, 5 and 7 for boys, and at age 6 for girls. Despite these differences, the individual dental development stages of 2020 and 2010 showed inconsistent trends with limited differences. Generally, girls demonstrate more advanced dental maturity than boys. A slight acceleration in Korean children’s dental maturity was observed over a 10-year period when comparing the 2020 groups to the 2010 groups.

With JWST’s successful deployment and unexpectedly high fuel reserves, measuring the masses of sub-Neptunes transiting bright, nearby stars will soon become the bottleneck for characterizing the atmospheres of small exoplanets via transmission spectroscopy. Using a carefully curated target list and observations from more than 2 yr of APF-Levy and Keck-HIRES Doppler monitoring, the TESS-Keck Survey is working toward alleviating this pressure. Here we present mass measurements for 11 transiting planets in eight systems that are particularly suited to atmospheric follow-up with JWST. We also report the discovery and confirmation of a temperate super-Jovian-mass planet on a moderately eccentric orbit. The sample of eight host stars, which includes one subgiant, spans early-K to late-F spectral types (T eff = 5200-6200 K). We homogeneously derive planet parameters using a joint photometry and radial velocity modeling framework, discuss the planets’ possible bulk compositions, and comment on their prospects for atmospheric characterization.

BackgroundAcute invasive fungal sinusitis (AIFS) is an aggressive disease that requires prompt diagnosis and multidisciplinary treatment given its rapid progression. However, there is currently no consensus on diagnosis, prognosis, and management strategies for AIFS, with multiple modalities routinely employed. The purpose of this multi-institutional and multidisciplinary evidence-based review with recommendations (EBRR) is to thoroughly review the literature on AIFS, summarize the existing evidence, and provide recommendations on the management of AIFS.MethodsThe PubMed, EMBASE, and Cochrane databases were systematically reviewed from inception through January 2022. Studies evaluating management for orbital, non-sinonasal head and neck, and intracranial manifestations of AIFS were included. An iterative review process was utilized in accordance with EBRR guidelines. Levels of evidence and recommendations on management principles for AIFS were generated.ResultsA review and evaluation of published literature was performed on 12 topics surrounding AIFS (signs and symptoms, laboratory and microbiology diagnostics, endoscopy, imaging, pathology, surgery, medical therapy, management of extrasinus extension, reversing immunosuppression, and outcomes and survival). The aggregate quality of evidence was varied across reviewed domains.ConclusionBased on the currently available evidence, judicious utilization of a combination of history and physical examination, laboratory and histopathologic techniques, and endoscopy provide the cornerstone for accurate diagnosis of AIFS. In addition, AIFS is optimally managed by a multidisciplinary team via a combination of surgery (including resection whenever possible), antifungal therapy, and correcting sources of immunosuppression. Higher quality (i.e., prospective) studies are needed to better define the roles of each modality and determine diagnosis and treatment algorithms.

Evidence for a flavor asymmetry between the ū and d¯ quark distributions in the proton has been found in deep-inelastic scattering and Drell-Yan experiments. The pronounced dependence of this flavor asymmetry on x (fraction of nucleon momentum carried by partons) observed in the Fermilab E866 Drell-Yan experiment suggested a drop of the d¯(x)/ū(x) ratio in the x>0.15 region. We report results from the SeaQuest Fermilab E906 experiment with improved statistical precision for d¯(x)/ū(x) in the large x region up to x=0.45 using the 120 GeV proton beam. Two different methods for extracting the Drell-Yan cross section ratios, σpd/2σpp, from the SeaQuest data give consistent results. The d¯(x)/ū(x) ratios and the d¯(x)-ū(x) differences are deduced from these cross section ratios for 0.13

Ibrutinib is a first-in-class Bruton's tyrosine kinase inhibitor approved for the treatment of various B-cell malignancies and chronic graft-versus-host disease. We evaluated the safety and efficacy of ibrutinib, alone or combined with standard-of-care regimens, in adults with advanced urothelial carcinoma (UC). Once-daily ibrutinib was administered orally at 840 mg (single-agent or with paclitaxel) or at 560 mg (with pembrolizumab). Phase 1b determined the recommended phase 2 dose (RP2D) of ibrutinib, and phase 2 assessed progression-free survival (PFS), overall response rate (ORR), and safety. Thirty-five, eighteen, and fifty-nine patients received ibrutinib, ibrutinib plus pembrolizumab, and ibrutinib plus paclitaxel at the RP2D, respectively. Safety profiles were consistent with those of the individual agents. The best-confirmed ORRs were 7% (two partial responses) with single-agent ibrutinib and 36% (five partial responses) with ibrutinib plus pembrolizumab. Median PFS was 4.1 months (range, 1.0-37.4+) with ibrutinib plus paclitaxel. The best-confirmed ORR was 26% (two complete responses). In previously treated patients with UC, ORR was higher with ibrutinib plus pembrolizumab than with either agent alone (historical data in the intent-to-treat population). ORR with ibrutinib plus paclitaxel was greater than historical values for single-agent paclitaxel or ibrutinib. These data warrant further evaluation of ibrutinib combinations in UC.

The complex cerebrovascular network is critical to controlling local cerebral blood flow (CBF) and maintaining brain homeostasis. Alzheimer's disease (AD) and neurological injury can result in impaired CBF regulation, blood-brain barrier breakdown, neurovascular dysregulation, and ultimately impaired brain homeostasis. Measuring cortical hemodynamic changes in rodents can help elucidate the complex physiological dynamics that occur in AD and neurological injury. Widefield optical imaging approaches can measure hemodynamic information, such as CBF and oxygenation. These measurements can be performed over fields of view that range from millimeters to centimeters and probe up to the first few millimeters of rodent brain tissue. We discuss the principles and applications of three widefield optical imaging approaches that can measure cerebral hemodynamics: (1) optical intrinsic signal imaging, (2) laser speckle imaging, and (3) spatial frequency domain imaging. Future work in advancing widefield optical imaging approaches and employing multimodal instrumentation can enrich hemodynamic information content and help elucidate cerebrovascular mechanisms that lead to the development of therapeutic agents for AD and neurological injury.

BackgroundThe gut-lung axis is generally recognized, but there are few large studies of the gut microbiome and incident respiratory disease in adults.ObjectiveWe sought to investigate the association and predictive capacity of the gut microbiome for incident asthma and chronic obstructive pulmonary disease (COPD).MethodsShallow metagenomic sequencing was performed for stool samples from a prospective, population-based cohort (FINRISK02; N = 7115 adults) with linked national administrative health register-derived classifications for incident asthma and COPD up to 15 years after baseline. Generalized linear models and Cox regressions were used to assess associations of microbial taxa and diversity with disease occurrence. Predictive models were constructed using machine learning with extreme gradient boosting. Models considered taxa abundances individually and in combination with other risk factors, including sex, age, body mass index, and smoking status.ResultsA total of 695 and 392 statistically significant associations were found between baseline taxonomic groups and incident asthma and COPD, respectively. Gradient boosting decision trees of baseline gut microbiome abundance predicted incident asthma and COPD in the validation data sets with mean area under the curves of 0.608 and 0.780, respectively. Cox analysis showed that the baseline gut microbiome achieved higher predictive performance than individual conventional risk factors, with C-indices of 0.623 for asthma and 0.817 for COPD. The integration of the gut microbiome and conventional risk factors further improved prediction capacities.ConclusionsThe gut microbiome is a significant risk factor for incident asthma and incident COPD and is largely independent of conventional risk factors.

AimsElevated lipoprotein(a) [Lp(a)] levels are associated with the risk of coronary artery disease (CAD) and calcific aortic valve stenosis (CAVS). Observational studies revealed that Lp(a) and C-reactive protein (CRP) levels, a biomarker of systemic inflammation, may jointly predict CAD risk. Whether Lp(a) and CRP levels also jointly predict CAVS incidence and progression is unknown.Methods and resultsWe investigated the association of Lp(a) with CAVS according to CRP levels in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk study (n = 18 226, 406 incident cases) and the UK Biobank (n = 438 260, 4582 incident cases), as well as in the ASTRONOMER study (n = 220), which assessed the haemodynamic progression rate of pre-existing mild-to-moderate aortic stenosis. In EPIC-Norfolk, in comparison to individuals with low Lp(a) levels (50 mg/dL) and low CRP levels (50 mg/dL) and elevated CRP levels (>2.0 mg/L) had a higher CAVS risk [hazard ratio (HR) = 1.86 (95% confidence intervals, 1.30-2.67) and 2.08 (1.44-2.99), respectively]. A comparable predictive value of Lp(a) in patients with vs. without elevated CRP levels was also noted in the UK Biobank. In ASTRONOMER, CAVS progression was comparable in patients with elevated Lp(a) levels with or without elevated CRP levels.ConclusionLp(a) predicts the incidence and possibly progression of CAVS regardless of plasma CRP levels. Lowering Lp(a) levels may warrant further investigation in the prevention and treatment of CAVS, regardless of systemic inflammation.

Inorganic arsenic (iAs) is an environmental toxicant that can lead to severe health consequences, which can be exacerbated if exposure occurs early in development. Here, we evaluated the impact of oral iAs treatment on UDP-glucuronosyltransferase 1A1 (UGT1A1) expression and bilirubin metabolism in humanized UGT1 (hUGT1) mice. We found that oral administration of iAs to neonatal hUGT1 mice that display severe neonatal hyperbilirubinemia leads to induction of intestinal UGT1A1 and a reduction in total serum bilirubin values. Oral iAs administration accelerates neonatal intestinal maturation, an event that is directly associated with UGT1A1 induction. As a reactive oxygen species producer, oral iAs treatment activated the Keap-Nrf2 pathway in the intestinal tract and liver. When Nrf2-deficient hUGT1 mice (hUGT1/Nrf2-/-) were treated with iAs, it was shown that activated Nrf2 contributed significantly toward intestinal maturation and UGT1A1 induction. However, hepatic UGT1A1 was not induced upon iAs exposure. We previously demonstrated that the nuclear receptor PXR represses liver UGT1A1 in neonatal hUGT1 mice. When PXR was deleted in hUGT1 mice (hUGT1/Pxr-/-), derepression of UGT1A1 was evident in both liver and intestinal tissue in neonates. Furthermore, when neonatal hUGT1/Pxr-/- mice were treated with iAs, UGT1A1 was superinduced in both tissues, confirming PXR release derepressed key regulatory elements on the gene that could be activated by iAs exposure. With iAs capable of generating reactive oxygen species in both liver and intestinal tissue, we conclude that PXR deficiency in neonatal hUGT1/Pxr-/- mice allows greater access of activated transcriptional modifiers such as Nrf2 leading to superinduction of UGT1A1.

Sedation is commonly used to relieve fear and anxiety during procedures. Dexmedetomidine (DEX), approved by the US Food and Drug Administration in 1999 for short-term sedation, is a selective alpha2-adrenoreceptor agonist. The use of DEX is increasing due to minimal respiratory depression and easy and quick awakening from sedation. Its sedative mechanisms are suggested to be related to changes in the interaction between brain regions. In this study, we used graph theory to investigate whether the altered network connection is associated with sedation. Electroencephalogram (EEG) recordings of 32 channels were acquired during awake and DEX-induced sedation for 20 participants. We extracted EEG epochs from the awake and the DEX sedation state. Using the graph theory, we compared the changes in the network connection parameters with the awake state. We observed that the slopes in 1/f dynamics, which indicate overall brain network characteristics, were greater during DEX-induced sedation compared to the awake state, suggesting a transition towards a random network behavior. In addition, network connections from the perspective of information processing were significantly disturbed in the alpha frequency band, unlike other frequency bands augmenting network connections. The alpha frequency band plays a prominent role in the function and interaction of cognitive activities. These results collectively indicate that changes in the brain network critical to cognition during DEX administration may also be related to the mechanism of sedation.

BackgroundPredict Breast (www.predict.nhs.uk) is an online prognostication and treatment benefit tool for early invasive breast cancer. The aim of this study was to incorporate the prognostic effect of progesterone receptor (PR) status into a new version of PREDICT and to compare its performance to the current version (2.2).MethodThe prognostic effect of PR status was based on the analysis of data from 45,088 European patients with breast cancer from 49 studies in the Breast Cancer Association Consortium. Cox proportional hazard models were used to estimate the hazard ratio for PR status. Data from a New Zealand study of 11,365 patients with early invasive breast cancer were used for external validation. Model calibration and discrimination were used to test the model performance.ResultsHaving a PR-positive tumour was associated with a 23% and 28% lower risk of dying from breast cancer for women with oestrogen receptor (ER)-negative and ER-positive breast cancer, respectively. The area under the ROC curve increased with the addition of PR status from 0.807 to 0.809 for patients with ER-negative tumours (p = 0.023) and from 0.898 to 0.902 for patients with ER-positive tumours (p = 2.3 × 10-6) in the New Zealand cohort. Model calibration was modest with 940 observed deaths compared to 1151 predicted.ConclusionThe inclusion of the prognostic effect of PR status to PREDICT Breast has led to an improvement of model performance and more accurate absolute treatment benefit predictions for individual patients. Further studies should determine whether the baseline hazard function requires recalibration.

PurposeTo provide precise age-specific risk estimates of cancers other than female breast and ovarian cancers associated with pathogenic variants (PVs) in BRCA1 and BRCA2 for effective cancer risk management.MethodsWe used data from 3,184 BRCA1 and 2,157 BRCA2 families in the Consortium of Investigators of Modifiers of BRCA1/2 to estimate age-specific relative (RR) and absolute risks for 22 first primary cancer types adjusting for family ascertainment.ResultsBRCA1 PVs were associated with risks of male breast (RR = 4.30; 95% CI, 1.09 to 16.96), pancreatic (RR = 2.36; 95% CI, 1.51 to 3.68), and stomach (RR = 2.17; 95% CI, 1.25 to 3.77) cancers. Associations with colorectal and gallbladder cancers were also suggested. BRCA2 PVs were associated with risks of male breast (RR = 44.0; 95% CI, 21.3 to 90.9), stomach (RR = 3.69; 95% CI, 2.40 to 5.67), pancreatic (RR = 3.34; 95% CI, 2.21 to 5.06), and prostate (RR = 2.22; 95% CI, 1.63 to 3.03) cancers. The stomach cancer RR was higher for females than males (6.89 v 2.76; P = .04). The absolute risks to age 80 years ranged from 0.4% for male breast cancer to approximately 2.5% for pancreatic cancer for BRCA1 carriers and from approximately 2.5% for pancreatic cancer to 27% for prostate cancer for BRCA2 carriers.ConclusionIn addition to female breast and ovarian cancers, BRCA1 and BRCA2 PVs are associated with increased risks of male breast, pancreatic, stomach, and prostate (only BRCA2 PVs) cancers, but not with the risks of other previously suggested cancers. The estimated age-specific risks will refine cancer risk management in men and women with BRCA1/2 PVs.

General anesthesia is critical for various procedures and surgeries. Despite the widespread use of anesthetics, their precise mechanisms remain poorly understood. Anesthetics inevitably act on the brain, primarily through the modulation of target receptors. Even if the action is specific to an individual neuron, however, long-range effects can occur due to the tremendous interconnectedness of neuronal activity. The strength of this connectivity can be understood using mathematical models that allow for the study of neuronal connectivity dynamics. These models also allow researchers to develop hypotheses on the candidate mechanisms of action of different types of anesthesia. This review highlights the theoretical background associated with the study of the mechanisms of action of anesthetics. We propose a candidate framework that describes how anesthetics act on the brain and consciousness in general.

In Fig. 1c of this Article, the x-axis scale was inadvertently duplicated from Fig. 1b. The original Article has been corrected online.

The United States’ transportation workforce is currently at a skills deficit in key areas. New and innovative transportation technologies and approaches threaten to exacerbate this situation. Yet, transportation workers need more than skills to implement new technologies: they need the skills to critically determine which technologies are likely to support a thriving nation and under what conditions. Additionally, transportation workers need the skills to support non-technology-focused solutions to the nation’s transportation challenges, including cultural, political, and social change.

Can people learn causal relationships about the world from someone’s emotions? We present a computational model integrating observational causal learning with emotional information, which uses emotional displays to disambiguate the beliefs, desires, and knowledge of other agents, in turn allowing causal inferences about the world. We compared our model predictions to human causal judgements on two observational learning tasks involving multiple possible causes or multiple possible outcomes. Across three studies (N = 129,127,125), emotional displays (compared to actions alone) led people to interpret agents’ beliefs differently, which in some contexts resulted in different causal inferences. Our model closely reflected these patterns of belief and causal inference and revealed new insights on how people learn causal relationships from others’ emotions.

PurposeTo evaluate the association between a previously published 313 variant-based breast cancer (BC) polygenic risk score (PRS313) and contralateral breast cancer (CBC) risk, in BRCA1 and BRCA2 pathogenic variant heterozygotes.MethodsWe included women of European ancestry with a prevalent first primary invasive BC (BRCA1 = 6,591 with 1,402 prevalent CBC cases; BRCA2 = 4,208 with 647 prevalent CBC cases) from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), a large international retrospective series. Cox regression analysis was performed to assess the association between overall and ER-specific PRS313 and CBC risk.ResultsFor BRCA1 heterozygotes the estrogen receptor (ER)-negative PRS313 showed the largest association with CBC risk, hazard ratio (HR) per SD = 1.12, 95% confidence interval (CI) (1.06-1.18), C-index = 0.53; for BRCA2 heterozygotes, this was the ER-positive PRS313, HR = 1.15, 95% CI (1.07-1.25), C-index = 0.57. Adjusting for family history, age at diagnosis, treatment, or pathological characteristics for the first BC did not change association effect sizes. For women developing first BC

PurposeTo evaluate the association between a previously published 313 variant-based breast cancer (BC) polygenic risk score (PRS313) and contralateral breast cancer (CBC) risk, in BRCA1 and BRCA2 pathogenic variant heterozygotes.MethodsWe included women of European ancestry with a prevalent first primary invasive BC (BRCA1 = 6,591 with 1,402 prevalent CBC cases; BRCA2 = 4,208 with 647 prevalent CBC cases) from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), a large international retrospective series. Cox regression analysis was performed to assess the association between overall and ER-specific PRS313 and CBC risk.ResultsFor BRCA1 heterozygotes the estrogen receptor (ER)-negative PRS313 showed the largest association with CBC risk, hazard ratio (HR) per SD = 1.12, 95% confidence interval (CI) (1.06-1.18), C-index = 0.53; for BRCA2 heterozygotes, this was the ER-positive PRS313, HR = 1.15, 95% CI (1.07-1.25), C-index = 0.57. Adjusting for family history, age at diagnosis, treatment, or pathological characteristics for the first BC did not change association effect sizes. For women developing first BC

PurposeThe purpose of this study was to develop an Asian polygenic risk score (PRS) to predict high myopia (HM) in Chinese children in the Singapore Cohort of Risk factors for Myopia (SCORM) cohort.MethodsWe included children followed from 6 to 11 years old until teenage years (12-18 years old). Cycloplegic autorefraction, ultrasound biometry, Illumina HumanHap 550, or 550 Duo Beadarrays, demographics, and environmental factors data were obtained. The PRS was generated from the Consortium for Refractive Error and Myopia genomewide association study (n = 542,934) and the Strabismus, Amblyopia, and Refractive Error in Singapore children Study (n = 500). The Growing Up in Singapore Towards healthy Outcomes Cohort study (n = 339) was the replication cohort. The outcome was teenage HM (≤ -5.00 D) with predictive performance assessed using the area under the curve (AUC).ResultsMean baseline age ± SD was 7.85 ± 0.84 (n = 1004) and 571 attended the teenage visit; 23.3% had HM. In multivariate analysis, the PRS was associated with a myopic spherical equivalent with an incremental R2 of 0.041 (95% confidence interval [CI] = 0.010, 0.073; P < 0.001). AUC for HM (0.77 [95% CI = 0.71-0.83]) performed better (P = 0.02) with the PRS compared with a model without (0.72 [95% CI = 0.65, 0.78]). Children at the top 25% PRS risk had a 2.34-fold-greater risk of HM (95% CI = 1.53, 3.55; P < 0.001).ConclusionsThe new Asian PRS improved the predictive performance to detect children at risk of HM.Translational relevanceClinicians may use the PRS with other predictive factors to identify high risk children and guide interventions to reduce the risk of HM later in life.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is initiated by binding of the viral Spike protein to host receptor angiotensin-converting enzyme 2 (ACE2), followed by fusion of viral and host membranes. Although antibodies that block this interaction are in emergency use as early coronavirus disease 2019 (COVID-19) therapies, the precise determinants of neutralization potency remain unknown. We discovered a series of antibodies that potently block ACE2 binding but exhibit divergent neutralization efficacy against the live virus. Strikingly, these neutralizing antibodies can inhibit or enhance Spike-mediated membrane fusion and formation of syncytia, which are associated with chronic tissue damage in individuals with COVID-19. As revealed by cryoelectron microscopy, multiple structures of Spike-antibody complexes have distinct binding modes that not only block ACE2 binding but also alter the Spike protein conformational cycle triggered by ACE2 binding. We show that stabilization of different Spike conformations leads to modulation of Spike-mediated membrane fusion with profound implications for COVID-19 pathology and immunity.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is initiated by binding of the viral Spike protein to host receptor angiotensin-converting enzyme 2 (ACE2), followed by fusion of viral and host membranes. Although antibodies that block this interaction are in emergency use as early coronavirus disease 2019 (COVID-19) therapies, the precise determinants of neutralization potency remain unknown. We discovered a series of antibodies that potently block ACE2 binding but exhibit divergent neutralization efficacy against the live virus. Strikingly, these neutralizing antibodies can inhibit or enhance Spike-mediated membrane fusion and formation of syncytia, which are associated with chronic tissue damage in individuals with COVID-19. As revealed by cryoelectron microscopy, multiple structures of Spike-antibody complexes have distinct binding modes that not only block ACE2 binding but also alter the Spike protein conformational cycle triggered by ACE2 binding. We show that stabilization of different Spike conformations leads to modulation of Spike-mediated membrane fusion with profound implications for COVID-19 pathology and immunity.

In the postnatal brain, neurogenesis occurs only within a few regions, such as the hippocampal sub-granular zone (SGZ). Postnatal neurogenesis is tightly regulated by factors that balance stem cell renewal with differentiation, and it gives rise to neurons that participate in learning and memory formation. The Kv1.1 channel, a voltage-gated potassium channel, was previously shown to suppress postnatal neurogenesis in the SGZ in a cell-autonomous manner. In this study, we have clarified the physiological and molecular mechanisms underlying Kv1.1-dependent postnatal neurogenesis. First, we discovered that the membrane potential of neural progenitor cells is highly dynamic during development. We further established a multinomial logistic regression model for cell-type classification based on the biophysical characteristics and corresponding cell markers. We found that the loss of Kv1.1 channel activity causes significant depolarization of type 2b neural progenitor cells. This depolarization is associated with increased tropomyosin receptor kinase B (TrkB) signaling and proliferation of neural progenitor cells; suppressing TrkB signaling reduces the extent of postnatal neurogenesis. Thus, our study defines the role of the Kv1.1 potassium channel in regulating the proliferation of postnatal neural progenitor cells in mouse hippocampus.

In the postnatal brain, neurogenesis occurs only within a few regions, such as the hippocampal sub-granular zone (SGZ). Postnatal neurogenesis is tightly regulated by factors that balance stem cell renewal with differentiation, and it gives rise to neurons that participate in learning and memory formation. The Kv1.1 channel, a voltage-gated potassium channel, was previously shown to suppress postnatal neurogenesis in the SGZ in a cell-autonomous manner. In this study, we have clarified the physiological and molecular mechanisms underlying Kv1.1-dependent postnatal neurogenesis. First, we discovered that the membrane potential of neural progenitor cells is highly dynamic during development. We further established a multinomial logistic regression model for cell-type classification based on the biophysical characteristics and corresponding cell markers. We found that the loss of Kv1.1 channel activity causes significant depolarization of type 2b neural progenitor cells. This depolarization is associated with increased tropomyosin receptor kinase B (TrkB) signaling and proliferation of neural progenitor cells; suppressing TrkB signaling reduces the extent of postnatal neurogenesis. Thus, our study defines the role of the Kv1.1 potassium channel in regulating the proliferation of postnatal neural progenitor cells in mouse hippocampus.

We measured the Rossiter-McLaughlin effect of WASP-107b during a single transit with Keck/HIRES. We found the sky-projected inclination of WASP-107b's orbit, relative to its host star's rotation axis, to be |λ| = 118+19-38degrees. This confirms the misaligned/polar orbit that was previously suggested from spot-crossing events and adds WASP-107b to the growing population of hot Neptunes in polar orbits around cool stars. WASP-107b is also the fourth such planet to have a known distant planetary companion. We examined several dynamical pathways by which this companion could have induced such an obliquity in WASP-107b. We find that nodal precession and disk dispersal-driven tilting can both explain the current orbital geometry while Kozai-Lidov cycles are suppressed by general relativity. While each hypothesis requires a mutual inclination between the two planets, nodal precession requires a much larger angle, which for WASP-107 is on the threshold of detectability with future Gaia astrometric data. As nodal precession has no stellar type dependence, but disk dispersal-driven tilting does, distinguishing between these two models is best done on the population level. Finding and characterizing more extrasolar systems like WASP-107 will additionally help distinguish whether the distribution of hot-Neptune obliquities is a dichotomy of aligned and polar orbits or if we are uniformly sampling obliquities during nodal precession cycles.

The fundamental building blocks of the proton-quarks and gluons-have been known for decades. However, we still have an incomplete theoretical and experimental understanding of how these particles and their dynamics give rise to the quantum bound state of the proton and its physical properties, such as its spin1. The two up quarks and the single down quark that comprise the proton in the simplest picture account only for a few per cent of the proton mass, the bulk of which is in the form of quark kinetic and potential energy and gluon energy from the strong force2. An essential feature of this force, as described by quantum chromodynamics, is its ability to create matter-antimatter quark pairs inside the proton that exist only for a very short time. Their fleeting existence makes the antimatter quarks within protons difficult to study, but their existence is discernible in reactions in which a matter-antimatter quark pair annihilates. In this picture of quark-antiquark creation by the strong force, the probability distributions as a function of momentum for the presence of up and down antimatter quarks should be nearly identical, given that their masses are very similar and small compared to the mass of the proton3. Here we provide evidence from muon pair production measurements that these distributions are considerably different, with more abundant down antimatter quarks than up antimatter quarks over a wide range of momenta. These results are expected to revive interest in several proposed mechanisms for the origin of this antimatter asymmetry in the proton that had been disfavoured by previous results4, and point to future measurements that can distinguish between these mechanisms.

The fundamental building blocks of the proton-quarks and gluons-have been known for decades. However, we still have an incomplete theoretical and experimental understanding of how these particles and their dynamics give rise to the quantum bound state of the proton and its physical properties, such as its spin1. The two up quarks and the single down quark that comprise the proton in the simplest picture account only for a few per cent of the proton mass, the bulk of which is in the form of quark kinetic and potential energy and gluon energy from the strong force2. An essential feature of this force, as described by quantum chromodynamics, is its ability to create matter-antimatter quark pairs inside the proton that exist only for a very short time. Their fleeting existence makes the antimatter quarks within protons difficult to study, but their existence is discernible in reactions in which a matter-antimatter quark pair annihilates. In this picture of quark-antiquark creation by the strong force, the probability distributions as a function of momentum for the presence of up and down antimatter quarks should be nearly identical, given that their masses are very similar and small compared to the mass of the proton3. Here we provide evidence from muon pair production measurements that these distributions are considerably different, with more abundant down antimatter quarks than up antimatter quarks over a wide range of momenta. These results are expected to revive interest in several proposed mechanisms for the origin of this antimatter asymmetry in the proton that had been disfavoured by previous results4, and point to future measurements that can distinguish between these mechanisms.

We report the discovery of TOI-561, a multiplanet system in the galactic thick disk that contains a rocky, ultrashort- period planet. This bright (V = 10.2) star hosts three small transiting planets identified in photometry from the NASA TESS mission: TOI-561 b (TOI-561.02, P = 0.44 days, Rp = 1.45 ± 0.11 R⊕), c (TOI-561.01, P = 10.8 days, Rp = 2.90 ± 0.13 R⊕), and d (TOI-561.03, P = 16.3 days, Rp = 2.32 ± 0.16 R⊕). The star is chemically ([Fe/ H] = -0.41 ± 0.05, [a/Fe]=+0.23 ± 0.05) and kinematically consistent with the galactic thick-disk population, making TOI-561 one of the oldest (10 ± 3 Gyr) and most metal-poor planetary systems discovered yet. We dynamically confirm planets b and c with radial velocities from the W. M. Keck Observatory High Resolution Echelle Spectrometer. Planet b has a mass and density of 3.2 ± 0.8M⊕ and 5.5+2.0-1.6g cm-3, consistent with a rocky composition. Its lower-than-average density is consistent with an iron-poor composition, although an Earth-like iron-to-silicates ratio is not ruled out. Planet c is 7.0 ± 2.3M⊕ and 1.6 ± 0.6 g cm-3, consistent with an interior rocky core overlaid with a low-mass volatile envelope. Several attributes of the photometry for planet d (which we did not detect dynamically) complicate the analysis, but we vet the planet with high-contrast imaging, groundbased photometric follow-up, and radial velocities. TOI-561 b is the first rocky world around a galactic thick-disk star confirmed with radial velocities and one of the best rocky planets for thermal emission studies.

In this study we aim to examine gene-environment interactions (GxEs) between genes involved with estrogen metabolism and environmental factors related to estrogen exposure. GxE analyses were conducted with 1970 Korean breast cancer cases and 2052 controls in the case-control study, the Seoul Breast Cancer Study (SEBCS). A total of 11,555 SNPs from the 137 candidate genes were included in the GxE analyses with eight established environmental factors. A replication test was conducted by using an independent population from the Breast Cancer Association Consortium (BCAC), with 62,485 Europeans and 9047 Asians. The GxE tests were performed by using two-step methods in GxEScan software. Two interactions were found in the SEBCS. The first interaction was shown between rs13035764 of NCOA1 and age at menarche in the GE|2df model (p-2df = 1.2 × 10-3). The age at menarche before 14 years old was associated with the high risk of breast cancer, and the risk was higher when subjects had homozygous minor allele G. The second GxE was shown between rs851998 near ESR1 and height in the GE|2df model (p-2df = 1.1 × 10-4). Height taller than 160 cm was associated with a high risk of breast cancer, and the risk increased when the minor allele was added. The findings were not replicated in the BCAC. These results would suggest specificity in Koreans for breast cancer risk.

HD 106315 and GJ 9827 are two bright, nearby stars that host multiple super-Earths and sub-Neptunes discovered by K2 that are well suited for atmospheric characterization. We refined the planets' ephemerides through Spitzer transits, enabling accurate transit prediction required for future atmospheric characterization through transmission spectroscopy. Through a multiyear high-cadence observing campaign with Keck/High Resolution Echelle Spectrometer and Magellan/Planet Finder Spectrograph, we improved the planets' mass measurements in anticipation of Hubble Space Telescope transmission spectroscopy. For GJ 9827, we modeled activity-induced radial velocity signals with a Gaussian process informed by the Calcium II H&K lines in order to more accurately model the effect of stellar noise on our data. We measured planet masses of Mb = 4.87 ± 0.37 M⊕, Mc = 1.92 ± 0.49 M⊕, and Md = 3.42 ± 0.62 M⊕. For HD 106315, we found that such activity radial velocity decorrelation was not effective due to the reduced presence of spots and speculate that this may extend to other hot stars as well (Teff > 6200 K). We measured planet masses of Mb = 10.5 ± 3.1 M⊕ and Mc = 12.0 ± 3.8 M⊕. We investigated all of the planets' compositions through comparison of their masses and radii to a range of interior models. GJ 9827 b and GJ 9827 c are both consistent with a 50/50 rock-iron composition, GJ 9827 d and HD 106315 b both require additional volatiles and are consistent with moderate amounts of water or hydrogen/helium, and HD 106315 c is consistent with a ∼10% hydrogen/helium envelope surrounding an Earth-like rock and iron core.

People have the fascinating ability to infer causality by observing other humans’ actions. We modelled this process using a Bayesian rational agent model and showed how people can reason about another agent’s beliefs and, by extension, infer the world’s causal structure. We compared the model’s predictions against humans’ causal judgements on a novel inference task. Participants (N = 171) were shown a dynamic scene depicting either a human agent, robot agent, or both agents acting on two objects sequentially before observing an outcome. After observing the human (vs the less intentional robot) agent, people were more likely to infer that both objects (in sequential order) caused the outcome. When two agents of different intentionality were shown, people favored the object that the intentional agent interacted with as the cause of the outcome. Our model captured these inference patterns well and revealed insights into reasoning about semi-intentional agents and multi-agent contexts.

BackgroundTo assess the genetic architecture of hypertrophic cardiomyopathy (HCM) in patients of predominantly Chinese ancestry.MethodsWe sequenced HCM disease genes in Singaporean patients (n=224) and Singaporean controls (n=3634), compared findings with additional populations and White HCM cohorts (n=6179), and performed in vitro functional studies.ResultsSingaporean HCM patients had significantly fewer confidently interpreted HCM disease variants (pathogenic/likely pathogenic: 18%, P

We report the measurement of a spectroscopic transit of TOI-1726c, one of two planets transiting a G-type star with V = 6.9 in the Ursa Major Moving Group (∼400 Myr). With a precise age constraint from cluster membership, TOI-1726 provides a great opportunity to test various obliquity excitation scenarios that operate on different timescales. By modeling the Rossiter-McLaughlin (RM) effect, we derived a sky-projected obliquity of -1-+3235∘. This result rules out a polar/retrograde orbit and is consistent with an aligned orbit for planet c. Considering the previously reported, similarly prograde RM measurement of planet b and the transiting nature of both planets, TOI-1726 tentatively conforms to the overall picture that compact multitransiting planetary systems tend to have coplanar, likely aligned orbits. TOI-1726 is also a great atmospheric target for understanding differential atmospheric loss of sub-Neptune planets (planet b 2.2 R☉ and c 2.7 R☉ both likely underwent photoevaporation). The coplanar geometry points to a dynamically cold history of the system that simplifies any future modeling of atmospheric escape.

Small planets on close-in orbits tend to exhibit envelope mass fractions of either effectively zero or up to a few percent depending on their size and orbital period. Models of thermally driven atmospheric mass loss and of terrestrial planet formation in a gas-poor environment make distinct predictions regarding the location of this rocky/nonrocky transition in period-radius space. Here we present the confirmation of TOI-1235 b (P = 3.44 days, rp1.738-0.076+0.087 R⊕), a planet whose size and period are intermediate between the competing model predictions, thus making the system an important test case for emergence models of the rocky/nonrocky transition around early M dwarfs (R s = 0.630± 0.015 ⊕, M s = 0.640 ± 0.016 ⊙. We confirm the TESS planet discovery using reconnaissance spectroscopy, ground-based photometry, high-resolution imaging, and a set of 38 precise radial velocities (RVs) from HARPS-N and HIRES. We measure a planet mass of 6.91-0.85+0.75M⊕ which implies an iron core mass fraction of 20-12+15% in the absence of a gaseous envelope. The bulk composition of TOI-1235 b is therefore consistent with being Earth-like, and we constrain an H/He envelope mass fraction to be

Although disinfection is key to infection control, the colonization patterns and resistomes of hospital-environment microbes remain underexplored. We report the first extensive genomic characterization of microbiomes, pathogens and antibiotic resistance cassettes in a tertiary-care hospital, from repeated sampling (up to 1.5 years apart) of 179 sites associated with 45 beds. Deep shotgun metagenomics unveiled distinct ecological niches of microbes and antibiotic resistance genes characterized by biofilm-forming and human-microbiome-influenced environments with corresponding patterns of spatiotemporal divergence. Quasi-metagenomics with nanopore sequencing provided thousands of high-contiguity genomes, phage and plasmid sequences (>60% novel), enabling characterization of resistome and mobilome diversity and dynamic architectures in hospital environments. Phylogenetics identified multidrug-resistant strains as being widely distributed and stably colonizing across sites. Comparisons with clinical isolates indicated that such microbes can persist in hospitals for extended periods (>8 years), to opportunistically infect patients. These findings highlight the importance of characterizing antibiotic resistance reservoirs in hospitals and establish the feasibility of systematic surveys to target resources for preventing infections.

Although disinfection is key to infection control, the colonization patterns and resistomes of hospital-environment microbes remain underexplored. We report the first extensive genomic characterization of microbiomes, pathogens and antibiotic resistance cassettes in a tertiary-care hospital, from repeated sampling (up to 1.5 years apart) of 179 sites associated with 45 beds. Deep shotgun metagenomics unveiled distinct ecological niches of microbes and antibiotic resistance genes characterized by biofilm-forming and human-microbiome-influenced environments with corresponding patterns of spatiotemporal divergence. Quasi-metagenomics with nanopore sequencing provided thousands of high-contiguity genomes, phage and plasmid sequences (>60% novel), enabling characterization of resistome and mobilome diversity and dynamic architectures in hospital environments. Phylogenetics identified multidrug-resistant strains as being widely distributed and stably colonizing across sites. Comparisons with clinical isolates indicated that such microbes can persist in hospitals for extended periods (>8 years), to opportunistically infect patients. These findings highlight the importance of characterizing antibiotic resistance reservoirs in hospitals and establish the feasibility of systematic surveys to target resources for preventing infections.

Recent years have seen increasing interest in the characterization of sub-Neptune-sized planets because of their prevalence in the Galaxy, contrasted with their absence in our solar system. HD 97658 is one of the brightest stars hosting a planet of this kind, and we present the transmission spectrum of this planet by combining four Hubble Space Telescope transits, 12 Spitzer/IRAC transits, and eight MOST transits of this system. Our transmission spectrum has a higher signal-to-noise ratio than those from previous works, and the result suggests that the slight increase in transit depth from wavelength 1.1-1.7 μm reported in previous works on the transmission spectrum of this planet is likely systematic. Nonetheless, our atmospheric modeling results are inconclusive, as no model provides an excellent match to our data. Nonetheless, we find that atmospheres with high C/O ratios (C/O ≈ 0.8) and metallicities of ≈100× solar metallicity are favored. We combine the mid-transit times from all of the new Spitzer and MOST observations and obtain an updated orbital period of P = 9.489295 ± 0.000005, with a best-fit transit time center at T 0 = 2456361.80690 ± 0.00038 (BJD). No transit timing variations are found in this system. We also present new measurements of the stellar rotation period (34 ± 2 days) and stellar activity cycle (9.6 yr) of the host star HD 97658. Finally, we calculate and rank the Transmission Spectroscopy Metric of all confirmed planets cooler than 1000 K and with sizes between 1 R ⊕ and 4 R ⊕. We find that at least a third of small planets cooler than 1000 K can be well characterized using James Webb Space Telescope, and of those, HD 97658b is ranked fifth, meaning that it remains a high-priority target for atmospheric characterization.

We report the detection of a Saturn-size exoplanet orbiting HD 332231 (TOI 1456) in light curves from the Transiting Exoplanet Survey Satellite (TESS). HD 332231 - an F8 dwarf star with a V-band magnitude of 8.56 - was observed by TESS in Sectors 14 and 15. We detect a single-transit event in the Sector 15 presearch data conditioning (PDC) light curve. We obtain spectroscopic follow-up observations of HD 332231 with the Automated Planet Finder, Keck I, and SONG telescopes. The orbital period we infer from radial velocity (RV) observations leads to the discovery of another transit in Sector 14 that was masked by PDC due to scattered light contamination. A joint analysis of the transit and RV data confirms the planetary nature of HD 332231 b, a Saturn-size (0.867-0.025+0.027RJ), sub-Saturn-mass (0.244±0.021MJ) exoplanet on a 18.71 day circular orbit. The low surface gravity of HD 332231 b and the relatively low stellar flux it receives make it a compelling target for transmission spectroscopy. Also, the stellar obliquity is likely measurable via the Rossiter-McLaughlin effect, an exciting prospect given the 0.14 au orbital separation of HD 332231 b. The spectroscopic observations do not provide substantial evidence for any additional planets in the HD 332231 system, but continued RV monitoring is needed to further characterize this system. We also predict that the frequency and duration of masked data in the PDC light curves for TESS Sectors 14-16 could hide transits of some exoplanets with orbital periods between 10.5 and 17.5 days.

Enhancing the efficacy of proteasome inhibitors (PI) is a central goal in myeloma therapy. We proposed that signaling-level responses after PI may reveal new mechanisms of action that can be therapeutically exploited. Unbiased phosphoproteomics after treatment with the PI carfilzomib surprisingly demonstrates the most prominent phosphorylation changes on splicing related proteins. Spliceosome modulation is invisible to RNA or protein abundance alone. Transcriptome analysis after PI demonstrates broad-scale intron retention, suggestive of spliceosome interference, as well as specific alternative splicing of protein homeostasis machinery components. These findings lead us to evaluate direct spliceosome inhibition in myeloma, which synergizes with carfilzomib and shows potent anti-tumor activity. Functional genomics and exome sequencing further support the spliceosome as a specific vulnerability in myeloma. Our results propose splicing interference as an unrecognized modality of PI mechanism, reveal additional modes of spliceosome modulation, and suggest spliceosome targeting as a promising therapeutic strategy in myeloma.

Enhancing the efficacy of proteasome inhibitors (PI) is a central goal in myeloma therapy. We proposed that signaling-level responses after PI may reveal new mechanisms of action that can be therapeutically exploited. Unbiased phosphoproteomics after treatment with the PI carfilzomib surprisingly demonstrates the most prominent phosphorylation changes on splicing related proteins. Spliceosome modulation is invisible to RNA or protein abundance alone. Transcriptome analysis after PI demonstrates broad-scale intron retention, suggestive of spliceosome interference, as well as specific alternative splicing of protein homeostasis machinery components. These findings lead us to evaluate direct spliceosome inhibition in myeloma, which synergizes with carfilzomib and shows potent anti-tumor activity. Functional genomics and exome sequencing further support the spliceosome as a specific vulnerability in myeloma. Our results propose splicing interference as an unrecognized modality of PI mechanism, reveal additional modes of spliceosome modulation, and suggest spliceosome targeting as a promising therapeutic strategy in myeloma.

PurposeThe Gartland extension-type supracondylar humerus (SCH) fracture is the most common paediatric elbow fracture. Treatment options range from nonoperative treatment (taping or casting) to operative treatments (closed reduction and percutaneous pinning or open reduction). Classification variability between surgeons is a potential contributing factor to existing controversy over treatment options for type II SCH fractures. This study investigated levels of agreement in extension-type SCH fracture classification using the modified Gartland classification system.MethodsA retrospective review was conducted on 60 patients aged between two and 12 years who had sustained an extension-type SCH fracture and received operative or nonoperative treatment at a tertiary children's hospital. Baseline radiographs were provided, and surgeons were asked to classify the fractures as type I, IIA, IIB or III according to the modified Gartland classification. Respondents were then asked to complete a second round of classifications using reshuffled radiographs. Weighted kappa values were calculated to assess interobserver and intraobserver levels of agreement.ResultsIn all, 21 paediatric orthopaedic surgeons responded to the survey and 15 completed a second round of ratings. Interobserver agreement for classification based on the Gartland criteria between surgeons was substantial with a kappa of 0.679 (95% confidence interval (CI) 0.501 to 0.873). Intraobserver agreement was substantial with a kappa of 0.796, (95% CI 0.628 to 0.864).ConclusionRadiographic classification of extension-type SCH fractures demonstrated substantial agreement both between and within surgeon raters. Therefore, classification variability may not be a major contributing factor to the treatment controversy for type II SCH fractures and treatment variability may be due to differences in surgeon preferences.Level of evidenceIII.

Planets occur most frequently around cool dwarfs, but only a handful of specific examples are known to orbit the latest-type M stars. Using TESS photometry, we report the discovery of two planets transiting the low-mass star called LP 791-18 (identified by TESS as TOI 736). This star has spectral type M6V, effective temperature 2960 K, and radius 0.17 R o, making it the third-coolest star known to host planets. The two planets straddle the radius gap seen for smaller exoplanets; they include a 1.1R ⊕ planet on a 0.95 day orbit and a 2.3R ⊕ planet on a 5 day orbit. Because the host star is small the decrease in light during these planets' transits is fairly large (0.4% and 1.7%). This has allowed us to detect both planets' transits from ground-based photometry, refining their radii and orbital ephemerides. In the future, radial velocity observations and transmission spectroscopy can both probe these planets' bulk interior and atmospheric compositions, and additional photometric monitoring would be sensitive to even smaller transiting planets.

Phonon polaritons in van der Waals materials reveal significant confinement accompanied with long propagation length: important virtues for tasks pertaining to the control of light and energy flow at the nanoscale. While previous studies of phonon polaritons have relied on relatively thick samples, here reported is the first observation of surface phonon polaritons in single atomic layers and bilayers of hexagonal boron nitride (hBN). Using antenna-based near-field microscopy, propagating surface phonon polaritons in mono- and bilayer hBN microcrystals are imaged. Phonon polaritons in monolayer hBN are confined in a volume about one million times smaller than the free-space photons. Both the polariton dispersion and their wavelength-thickness scaling law are altered compared to those of hBN bulk counterparts. These changes are attributed to phonon hardening in monolayer-thick crystals. The data reported here have bearing on applications of polaritons in metasurfaces and ultrathin optical elements.

Phonon polaritons in van der Waals materials reveal significant confinement accompanied with long propagation length: important virtues for tasks pertaining to the control of light and energy flow at the nanoscale. While previous studies of phonon polaritons have relied on relatively thick samples, here reported is the first observation of surface phonon polaritons in single atomic layers and bilayers of hexagonal boron nitride (hBN). Using antenna-based near-field microscopy, propagating surface phonon polaritons in mono- and bilayer hBN microcrystals are imaged. Phonon polaritons in monolayer hBN are confined in a volume about one million times smaller than the free-space photons. Both the polariton dispersion and their wavelength-thickness scaling law are altered compared to those of hBN bulk counterparts. These changes are attributed to phonon hardening in monolayer-thick crystals. The data reported here have bearing on applications of polaritons in metasurfaces and ultrathin optical elements.