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ObjectiveDecoding neural activity has been limited by the lack of tools available to record from large numbers of neurons across multiple cortical regions simultaneously with high temporal fidelity. To this end, we developed the Argo system to record cortical neural activity at high data rates.ApproachHere we demonstrate a massively parallel neural recording system based on platinum-iridium microwire electrode arrays bonded to a CMOS voltage amplifier array. The Argo system is the highest channel count in vivo neural recording system, supporting simultaneous recording from 65 536 channels, sampled at 32 kHz and 12-bit resolution. This system was designed for cortical recordings, compatible with both penetrating and surface microelectrodes.Main resultsWe validated this system through initial bench testing to determine specific gain and noise characteristics of bonded microwires, followed by in-vivo experiments in both rat and sheep cortex. We recorded spiking activity from 791 neurons in rats and surface local field potential activity from over 30 000 channels in sheep.SignificanceThese are the largest channel count microwire-based recordings in both rat and sheep. While currently adapted for head-fixed recording, the microwire-CMOS architecture is well suited for clinical translation. Thus, this demonstration helps pave the way for a future high data rate intracortical implant.

It is well known that the ambient environment can dramatically renormalize the quasiparticle gap and exciton binding energies in low-dimensional materials, but the effect of the environment on the energy splitting of the spin-singlet and spin-triplet exciton states is less understood. A prominent effect is the renormalization of the exciton binding energy and optical strength (and hence the optical spectrum) through additional screening of the direct Coulomb term describing the attractive electron-hole interaction in the kernel of the Bethe-Salpeter equation. The repulsive exchange interaction responsible for the singlet-triplet splitting, on the other hand, is unscreened within formal many-body perturbation theory. However, Benedict argued that in practical calculations restricted to a subspace of the full Hilbert space, the exchange interaction should be appropriately screened by states outside of the subspace, the so-called S approximation [L. X. Benedict, Phys. Rev. B 66, 193105 (2002)PRBMDO0163-182910.1103/PhysRevB.66.193105]. Here, we systematically explore the accuracy of the S approximation for different confined systems, including a molecule and heterostructures of semiconducting and metallic layered materials. We show that the S approximation is actually exact in the limit of small exciton binding energies (i.e., small direct term) and can be used to significantly accelerate convergence of the exciton energies with respect to the number of empty states, provided that a particular effective screening consistent with the conventional Tamm-Dancoff approximation is employed. We further find that the singlet-triplet splitting in the energy of the excitons is largely unaffected by the external dielectric environment for most quasi-two-dimensional materials.

The American Thoracic Society Core Curriculum updates clinicians annually in adult and pediatric pulmonary disease, medical critical care, and sleep medicine, in a 3- to 4-year recurring cycle of topics. These topics will be presented at the 2020 International Conference. Below is the pediatric pulmonary medicine core, including pediatric hypoxemic respiratory failure; modalities in noninvasive management of chronic respiratory failure in childhood; surgical and nonsurgical management of congenital lung malformations; an update on smoke inhalation lung injury; an update on vaporizers, e-cigarettes, and other electronic delivery systems; pulmonary complications of sarcoidosis; pulmonary complications of congenital heart disease; and updates on the management of congenital diaphragmatic hernia.

Molluscs often possess complex calcified elements in addition to the shell, but how these elements function and relate to other tissues is often poorly understood. Dorid nudibranchs typically possess innumerable calcareous spicules arranged in complex networks. To describe how these spicules interact with muscles and connective tissue, we reconstructed tomographic digital models using serial sections and synchrotron micro-computed tomography. In two species with dramatically different spicule network morphologies, musculature was divided into a dorsal layer of crossed fibres, a ventral layer of branching radial fibres, and scattered dorsoventral fibres in between. These two species differed in the size of their dorsal tubercles, which was reflected in the organization of dorsal musculature, and in the amount and organization of connective tissue. In Platydoris sanguinea Bergh, 1905, dense mats of spicules sandwiched a layer of connective tissue with fewer spicules and muscle insertions only onto the ventral spicules. In Cadlina luteomarginata MacFarland, 1966, thick tracts of spicules are surrounded by a sheath of connective tissue. Muscles surround and insert into the dorsal tubercle spicule layer. Thus, both species appear to use the spicule network for muscle antagonism and transfer of motion, but the different arrangement of elements suggests that they use this skeleton in quite different ways.

In this work we focus on neurodiversity, a recently defined facet of diversity. Chemical education is in its early stages of recognizing the value that neurodiversity brings to the field. After an overview of current terminology, we discuss general challenges that neurodivergent students face in chemistry classes. To create an inclusive class experience for students with diverse neurocognitive functioning, we focus on increasing learner agency. Our premise is that neurodiversity is supported by a well-structured, learner-driven class-experience. On the basis of this, we developed a design that we applied in nonmajor chemistry courses taught remotely due to the COVID-19 pandemic. Our premise is supported by data extracted from student-teacher interactions, student surveys, and student course evaluations.

Objective: Dissection of the dorsal nerves of the clitoris (DNC) is an important step in most gender-affirming phalloplasty techniques. Understanding DNC anatomy also facilitates safe vulvar and clitoral surgery. However, the surgical anatomy of the DNC has only recently been thoroughly described in the literature, and dissection of the DNC has not traditionally been a routine part of genitourinary surgical education.1,2 With procedures involving the DNC (e.g. gender-affirming phalloplasty) increasing in frequency, surgical resources are needed to better illustrate and teach this critical dissection. In this video, we demonstrate a safe, efficient and reliable approach to dissection of the DNC. Patients and surgical procedure: This video is a demonstration of an approach to dissection of the dorsal nerve of the clitoris in a gender-affirming phalloplasty procedure. Results: The DNC is a critical structure for erogenous and sexual function and its dissection should always be approached cautiously to avoid injury. The DNC is formed from branches of the pudendal nerve and travels below the inferior public ramus along the posterior edge of the clitoral crus [3]. Inferior to the pubic symphysis, at the angle of the clitoral body, the dorsal clitoral nerves enter the deep component of the suspensory ligament of the clitoris.1,2 At the base of the clitoral body the dorsal nerves are superiorly suspended away from the clitoris before they descend inferiorly along the clitoral body. At this level, the DNC are large, approximately 2–3.2 mm, traveling at 10-11 and 1-2 o'clock positions along the clitoral body. We approach the DNC at this level by releasing the suspensory ligament of the clitoris and dissecting through the clitoral fascia. Conclusions: Dissection of the dorsal nerve of the clitoris (DNC) is a critical step in many gender-affirming phalloplasty procedures. A thorough understanding of its surgical anatomy is also necessary for safe vulvar surgery. In this video, we demonstrate a safe, efficient and reliable approach to dissection of the DNC.

Rapid and accurate detection of the pathogens, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for COVID-19, is critical for mitigating the COVID-19 pandemic. Current state-of-the-art pathogen tests for COVID-19 diagnosis are done in a liquid medium and take 10–30 min for rapid antigen tests and hours to days for polymerase chain reaction (PCR) tests. Herein we report novel accurate pathogen sensors, a new test method, and machine-learning algorithms for a breathalyzer platform for fast detection of SARS-CoV-2 virion particles in the aerosol in 30 s. The pathogen sensors are based on a functionalized molecularly-imprinted polymer, with the template molecules being the receptor binding domain spike proteins for different variants of SARS-CoV-2. Sensors are tested in the air and exposed for 10 s to the aerosols of various types of pathogens, including wild-type, D614G, alpha, delta, and omicron variant SARS-CoV-2, BSA (Bovine serum albumin), Middle East respiratory syndrome–related coronavirus (MERS-CoV), influenza, and wastewater samples from local sewage. Our low-cost, fast-responsive pathogen sensors yield accuracy above 99% with a limit-of-detection (LOD) better than 1 copy/μL for detecting the SARS-CoV-2 virus from the aerosol. The machine-learning algorithm supporting these sensors can accurately detect the pathogens, thereby enabling a new and unique breathalyzer platform for rapid COVID-19 tests with unprecedented speeds.

The precise measurement of the spectrum of protons, the most abundant component of the cosmic radiation, is necessary to understand the source and acceleration of cosmic rays in the Milky Way. This work reports the measurement of the cosmic ray proton fluxes with kinetic energies from 40 GeV to 100 TeV, with 2 1/2 years of data recorded by the DArk Matter Particle Explorer (DAMPE). This is the first time that an experiment directly measures the cosmic ray protons up to ~100 TeV with high statistics. The measured spectrum confirms the spectral hardening at ~300 GeV found by previous experiments and reveals a softening at ~13.6 TeV, with the spectral index changing from ~2.60 to ~2.85. Our result suggests the existence of a new spectral feature of cosmic rays at energies lower than the so-called knee and sheds new light on the origin of Galactic cosmic rays.

The precise measurement of the spectrum of protons, the most abundant component of the cosmic radiation, is necessary to understand the source and acceleration of cosmic rays in the Milky Way. This work reports the measurement of the cosmic ray proton fluxes with kinetic energies from 40 GeV to 100 TeV, with 2 1/2 years of data recorded by the DArk Matter Particle Explorer (DAMPE). This is the first time that an experiment directly measures the cosmic ray protons up to ~100 TeV with high statistics. The measured spectrum confirms the spectral hardening at ~300 GeV found by previous experiments and reveals a softening at ~13.6 TeV, with the spectral index changing from ~2.60 to ~2.85. Our result suggests the existence of a new spectral feature of cosmic rays at energies lower than the so-called knee and sheds new light on the origin of Galactic cosmic rays.

LUX-ZEPLIN (LZ) is a second-generation direct dark matter experiment with spin-independent WIMP-nucleon scattering sensitivity above 1.4×10-48cm2 for a WIMP mass of 40GeV/c2 and a 1000days exposure. LZ achieves this sensitivity through a combination of a large 5.6t fiducial volume, active inner and outer veto systems, and radio-pure construction using materials with inherently low radioactivity content. The LZ collaboration performed an extensive radioassay campaign over a period of six years to inform material selection for construction and provide an input to the experimental background model against which any possible signal excess may be evaluated. The campaign and its results are described in this paper. We present assays of dust and radon daughters depositing on the surface of components as well as cleanliness controls necessary to maintain background expectations through detector construction and assembly. Finally, examples from the campaign to highlight fixed contaminant radioassays for the LZ photomultiplier tubes, quality control and quality assurance procedures through fabrication, radon emanation measurements of major sub-systems, and bespoke detector systems to assay scintillator are presented.

BackgroundNo therapies for targeting KRAS mutations in cancer have been approved. The KRAS p.G12C mutation occurs in 13% of non-small-cell lung cancers (NSCLCs) and in 1 to 3% of colorectal cancers and other cancers. Sotorasib is a small molecule that selectively and irreversibly targets KRASG12C.MethodsWe conducted a phase 1 trial of sotorasib in patients with advanced solid tumors harboring the KRAS p.G12C mutation. Patients received sotorasib orally once daily. The primary end point was safety. Key secondary end points were pharmacokinetics and objective response, as assessed according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.ResultsA total of 129 patients (59 with NSCLC, 42 with colorectal cancer, and 28 with other tumors) were included in dose escalation and expansion cohorts. Patients had received a median of 3 (range, 0 to 11) previous lines of anticancer therapies for metastatic disease. No dose-limiting toxic effects or treatment-related deaths were observed. A total of 73 patients (56.6%) had treatment-related adverse events; 15 patients (11.6%) had grade 3 or 4 events. In the subgroup with NSCLC, 32.2% (19 patients) had a confirmed objective response (complete or partial response) and 88.1% (52 patients) had disease control (objective response or stable disease); the median progression-free survival was 6.3 months (range, 0.0+ to 14.9 [with + indicating that the value includes patient data that were censored at data cutoff]). In the subgroup with colorectal cancer, 7.1% (3 patients) had a confirmed response, and 73.8% (31 patients) had disease control; the median progression-free survival was 4.0 months (range, 0.0+ to 11.1+). Responses were also observed in patients with pancreatic, endometrial, and appendiceal cancers and melanoma.ConclusionsSotorasib showed encouraging anticancer activity in patients with heavily pretreated advanced solid tumors harboring the KRAS p.G12C mutation. Grade 3 or 4 treatment-related toxic effects occurred in 11.6% of the patients. (Funded by Amgen and others; CodeBreaK100 ClinicalTrials.gov number, NCT03600883.).

BackgroundRET fusions are oncogenic drivers in 1 to 2% of non-small-cell lung cancers (NSCLCs). In patients with RET fusion-positive NSCLC, the efficacy and safety of selective RET inhibition are unknown.MethodsWe enrolled patients with advanced RET fusion-positive NSCLC who had previously received platinum-based chemotherapy and those who were previously untreated separately in a phase 1-2 trial of selpercatinib. The primary end point was an objective response (a complete or partial response) as determined by an independent review committee. Secondary end points included the duration of response, progression-free survival, and safety.ResultsIn the first 105 consecutively enrolled patients with RET fusion-positive NSCLC who had previously received at least platinum-based chemotherapy, the percentage with an objective response was 64% (95% confidence interval [CI], 54 to 73). The median duration of response was 17.5 months (95% CI, 12.0 to could not be evaluated), and 63% of the responses were ongoing at a median follow-up of 12.1 months. Among 39 previously untreated patients, the percentage with an objective response was 85% (95% CI, 70 to 94), and 90% of the responses were ongoing at 6 months. Among 11 patients with measurable central nervous system metastasis at enrollment, the percentage with an objective intracranial response was 91% (95% CI, 59 to 100). The most common adverse events of grade 3 or higher were hypertension (in 14% of the patients), an increased alanine aminotransferase level (in 12%), an increased aspartate aminotransferase level (in 10%), hyponatremia (in 6%), and lymphopenia (in 6%). A total of 12 of 531 patients (2%) discontinued selpercatinib because of a drug-related adverse event.ConclusionsSelpercatinib had durable efficacy, including intracranial activity, with mainly low-grade toxic effects in patients with RET fusion-positive NSCLC who had previously received platinum-based chemotherapy and those who were previously untreated. (Funded by Loxo Oncology and others; LIBRETTO-001 ClinicalTrials.gov number, NCT03157128.).

We present the G0W0 band structure, core levels, and deformation potential of monolayer FeSe in the paramagnetic phase based on a starting mean field of the Kohn-Sham density functional theory (DFT) with the Perdew, Burke, and Ernzerhof functional. We find the GW correction increases the bandwidth of the states forming the M pocket near the Fermi energy, while leaving the Γ pocket roughly unchanged. We then compare the G0W0 quasiparticle band energies with the band structure from a simple empirical +A approach, which was recently proposed to capture the renormalization of the electron-phonon interaction going beyond DFT in FeSe, when used as a starting point in density functional perturbation theory. We show that this empirical correction succeeds in approximating the GW nonlocal and dynamical self-energy in monolayer FeSe and reproduces the GW band structure near the Fermi surface, the core energy levels, and the deformation potential (electron-phonon coupling).

COPD is a heterogeneous syndrome. Many COPD subtypes have been proposed, but there is not yet consensus on how many COPD subtypes there are and how they should be defined. The COPD Genetic Epidemiology Study (COPDGene), which has generated 10-year longitudinal chest imaging, spirometry, and molecular data, is a rich resource for relating COPD phenotypes to underlying genetic and molecular mechanisms. In this article, we place COPDGene clustering studies in context with other highly cited COPD clustering studies, and summarize the main COPD subtype findings from COPDGene. First, most manifestations of COPD occur along a continuum, which explains why continuous aspects of COPD or disease axes may be more accurate and reproducible than subtypes identified through clustering methods. Second, continuous COPD-related measures can be used to create subgroups through the use of predictive models to define cut-points, and we review COPDGene research on blood eosinophil count thresholds as a specific example. Third, COPD phenotypes identified or prioritized through machine learning methods have led to novel biological discoveries, including novel emphysema genetic risk variants and systemic inflammatory subtypes of COPD. Fourth, trajectory-based COPD subtyping captures differences in the longitudinal evolution of COPD, addressing a major limitation of clustering analyses that are confounded by disease severity. Ongoing longitudinal characterization of subjects in COPDGene will provide useful insights about the relationship between lung imaging parameters, molecular markers, and COPD progression that will enable the identification of subtypes based on underlying disease processes and distinct patterns of disease progression, with the potential to improve the clinical relevance and reproducibility of COPD subtypes.

This Article has been retracted; see accompanying Retraction Note.

We describe the design and assembly of the LUX-ZEPLIN experiment, a direct detection search for cosmic WIMP dark matter particles. The centerpiece of the experiment is a large liquid xenon time projection chamber sensitive to low energy nuclear recoils. Rejection of backgrounds is enhanced by a Xe skin veto detector and by a liquid scintillator Outer Detector loaded with gadolinium for efficient neutron capture and tagging. LZ is located in the Davis Cavern at the 4850’ level of the Sanford Underground Research Facility in Lead, South Dakota, USA. We describe the major subsystems of the experiment and its key design features and requirements.

The micrometer-scale reticulated structure of highly sulfur-philic nitrogen-doped graphene oxide (NrGO) that is achieved by chemically controlling the nitrogen-doping degree improves the chemical and electrochemical stability of the active sulfur while providing sufficient sulfur/electrolyte interface for a facile electrochemical process so that a high specific energy of 325 W h kg-1 can be achieved.

Functioning bulk-type all-solid-state batteries in a practical form factor with composite positive electrodes, using Al-substituted Li7La3Zr2O12 (LLZO) as the solid electrolyte, have been demonstrated for the first time. The devices incorporate bilayers composed of dense LLZO membranes and porous LLZO scaffolds infiltrated with LiNi0.6Mn0.2Co0.2O2 and other components as positive electrodes, combined with lithium anodes. The porous scaffolds are prepared using an easily scaled freeze-tape-casting method. The unidirectional pores of the scaffold facilitate infiltration of cathode components and shorten lithium ion diffusion path lengths, while the addition of a soft ionically conductive solid to the scaffold ensures good contact among the components.

Lithium metal is a high-energy-density battery electrode material, but the largely irreversible growth of lithium protrusions on an initially planar electrode during cycling makes it unsuitable for incorporation into a commercial battery. In this study, a lithium electrode with globular protrusions was stripped electrochemically, and the local morphology of the electrode as a function of time was determined by hard X-ray tomography. We demonstrate that globules are preferentially stripped compared to a planar electrode in our system, which incorporates a nanostructured block copolymer electrolyte. We report current density at the electrode as a function of micron-scale position and time. The local current density during the electrode healing process calculated from a reference frame at the electrode/electrolyte interface provides insight into the driving forces responsible for selective stripping of the globule. These results imply the possibility of discharging protocols that may return a lithium electrode to its initial planar state.

Most of the work on Lithium-sulfur (LiS) batteries use liquid electrolytes that have limited stability when coupled with Li metal anodes. We have studied LiS batteries with a solid block copolymer electrolyte which exhibits improved stability against Li anodes. The electrolyte comprises a polystyrene-b-poly(ethylene oxide) (SEO) copolymer doped with a Li salt. Hollow carbon nanospheres impregnated with sulfur were used to build a composite cathode. Two types of sulfur-impregnated functionalized carbon nanospheres were used: One with carboxylic acid groups and the other with short lithium poly(4-styrenesulfonyl(trifluoromethylsulfonyl)imide) (PSTFSI-Li) chains. Cells with Li2S8 dissolved in the SEO based electrolyte served as the baseline. After cycling, the reason for capacity fade was determined by imaging the batteries using synchrotron hard X-ray microtomography. It is generally assumed that LiS cells fail due to dissolution of polysulfide into the liquid electrolyte, i.e., the main problems related to the cathode. In our all-solid cells, failure was primarily due to delamination of the Li foil from the polymer electrolyte layer. Delamination is also observed at the sulfur cathode. It is likely that the large changes in volume of the active materials during cycling induce delamination in all-solid LiS cells.