A versatile laser-based apparatus for time-resolved ARPES with micro-scale spatial resolution.

We present the development of a versatile apparatus for 6.2 eV laser-based time and angle-resolved photoemission spectroscopy with micrometer spatial resolution (time-resolved µ-ARPES). With a combination of tunable spatial resolution down to ∼11 µm, high energy resolution (∼11 meV), near-transform-limited temporal resolution (∼280 fs), and tunable 1.55 eV pump fluence up to 3 mJ/cm2, this time-resolved µ-ARPES system enables the measurement of ultrafast electron dynamics in exfoliated and inhomogeneous materials. We demonstrate the performance of our system by correlating the spectral broadening of the topological surface state of Bi2Se3 with the spatial dimension of the probe pulse, as well as resolving the spatial inhomogeneity contribution to the observed spectral broadening. Finally, after in situ exfoliation, we performed time-resolved µ-ARPES on a ∼30 µm flake of transition metal dichalcogenide WTe2, thus demonstrating the ability to access ultrafast electron dynamics with momentum resolution on micro-exfoliated materials.

Reduced mitophagy is an early feature of NAFLD and liver-specific PARKIN knockout hastens the onset of steatosis, inflammation and fibrosis.

Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of pathologies that includes steatosis, steatohepatitis (NASH) and fibrosis and is strongly associated with insulin resistance and type 2 diabetes. Changes in mitochondrial function are implicated in the pathogenesis of NAFLD, particularly in the transition from steatosis to NASH. Mitophagy is a mitochondrial quality control mechanism that allows for the selective removal of damaged mitochondria from the cell via the autophagy pathway. While past work demonstrated a negative association between liver fat content and rates of mitophagy, when changes in mitophagy occur during the pathogenesis of NAFLD and whether such changes contribute to the primary endpoints associated with the disease are currently poorly defined. We therefore undertook the studies described here to establish when alterations in mitophagy occur during the pathogenesis of NAFLD, as well as to determine the effects of genetic inhibition of mitophagy via conditional deletion of a key mitophagy regulator, PARKIN, on the development of steatosis, insulin resistance, inflammation and fibrosis. We find that loss of mitophagy occurs early in the pathogenesis of NAFLD and that loss of PARKIN accelerates the onset of key NAFLD disease features. These observations suggest that loss of mitochondrial quality control in response to nutritional stress may contribute to mitochondrial dysfunction and the pathogenesis of NAFLD.

Finding Order in Chaos: Quantitative Predictors of Chaos Terrain Morphology on Europa.

The mechanisms for chaos terrain formation on Europa have long been a source of debate in the scientific community. There exist numerous theoretical and numerical models for chaos formation, but to date there has been a lack of quantifiable observations that can be used to constrain models and permit comparison to the outputs of these chaos models. Here, we use mapping and statistical analysis to develop a quantitative description of chaos terrain and their observed morphologies. For nine chaos features, we map every block, or region of pre-existing terrain within disrupted matrix. We demonstrate that chaos terrains follow a continuous spectrum of morphologies between two endmembers, platy and knobby. We find that any given chaos terrain's morphology can be quantified by means of the linearized exponential slope of its cumulative block area distribution. This quantitative metric provides a new diagnostic parameter in future studies of chaos terrain formation and comparison.

A modular spring-loaded actuator for mechanical activation of membrane proteins.

How cells respond to mechanical forces by converting them into biological signals underlie crucial cellular processes. Our understanding of mechanotransduction has been hindered by technical barriers, including limitations in our ability to effectively apply low range piconewton forces to specific mechanoreceptors on cell membranes without laborious and repetitive trials. To overcome these challenges we introduce the Nano-winch, a robust, easily assembled, programmable DNA origami-based molecular actuator. The Nano-winch is designed to manipulate multiple mechanoreceptors in parallel by exerting fine-tuned, low- piconewton forces in autonomous and remotely activated modes via adjustable single- and double-stranded DNA linkages, respectively. Nano-winches in autonomous mode can land and operate on the cell surface. Targeting the device to integrin stimulated detectable downstream phosphorylation of focal adhesion kinase, an indication that Nano-winches can be applied to study cellular mechanical processes. Remote activation mode allowed finer extension control and greater force exertion. We united remotely activated Nano-winches with single-channel bilayer experiments to directly observe the opening of a channel by mechanical force in the force responsive gated channel protein, BtuB. This customizable origami provides an instrument-free approach that can be applied to control and explore a diversity of mechanotransduction circuits on living cells.

Optical manipulation of Rashba-split 2-dimensional electron gas.

In spintronics, the two main approaches to actively control the electrons' spin involve static magnetic or electric fields. An alternative avenue relies on the use of optical fields to generate spin currents, which can bolster spin-device performance, allowing for faster and more efficient logic. To date, research has mainly focused on the optical injection of spin currents through the photogalvanic effect, and little is known about the direct optical control of the intrinsic spin-splitting. To explore the optical manipulation of a material's spin properties, we consider the Rashba effect. Using time- and angle-resolved photoemission spectroscopy (TR-ARPES), we demonstrate that an optical excitation can tune the Rashba-induced spin splitting of a two-dimensional electron gas at the surface of Bi2Se3. We establish that light-induced photovoltage and charge carrier redistribution - which in concert modulate the Rashba spin-orbit coupling strength on a sub-picosecond timescale - can offer an unprecedented platform for achieving optically-driven spin logic devices.

Command, control and communication (C3) during the COVID-19 pandemic; adapting a military framework to crisis response in a tertiary UK critical care centre.

The COVID-19 pandemic of 2020 imposed significant strain on critical care services worldwide. The South London region experienced the largest numbers of critical care admissions in the United Kingdom with King's College Hospital one of the busiest centres. This article outlines, using a descriptive narrative, the significant changes that occurred within King's Critical Care as a result of the pandemic and the decisions that were taken to provide effective co-ordination and control to the expanded service, in part drawing on the military experience of two of the authors. The wider context of crisis and major incident leadership and management is also discussed contrasting different approaches used in civilian and military settings.

A resistive-anode based position-sensitive Rydberg atom detector.

We describe here the development and characterization of a position-sensitive detector for Rydberg atom experiments. The detector builds on an earlier design that field-ionized incident Rydberg positronium (Ps) atoms and then electrostatically focused the freed positrons onto a micro-channel plate (MCP) detector without the use of a position sensitive anode. In this design, pulses from the MCP are deposited onto a resistive anode, providing a means of measuring the incident particles' x, y positions. The first detector constructed utilized a pair of MCPs in a chevron configuration and was used to observe the focusing of Rydberg Ps atoms from an electrostatic mirror. A second detector, developed for use in a measurement of the 1S-2S interval of Ps, incorporates three MCPs in a Z-stack configuration to produce larger pulses. Using a UV-induced signal, we have characterized the performance of the assembled detectors, finding a spatial resolution of ∼1.4 mm for the largest induced pulses and for pulse widths of ∼7-10 ns FWHM; pulse times can be resolved to better than 1 ns. The Ps induced signal is anticipated to yield pulses ∼5 times larger, which are expected to achieve a spatial resolution of <1 mm. Appropriate lenses could make possible applications involving either imaging a large area or magnifying a small area of the incident Ps spatial distribution.

Domain-general and domain-specific influences on emerging numerical cognition: Contrasting uni-and bidirectional prediction models.

Domain-general skills such as executive functions (EFs), and domain-specific skills such as non-symbolic number sense and symbolic understanding are often pitted against each other as predictors of emerging maths. Here we aimed to investigate early childhood relations between these foundational skills with a balanced, longitudinal design. One hundred and seventy 3- and 4-year-old-children were tested at two time points, 5 months apart, on four domain-general executive and five domain-specific numeracy tasks. A latent EF factor was a strong predictor of symbolic maths and of their growth. In addition, stronger symbolic maths at Time 1 was correlated with later stronger EF, but symbolic maths did not predict EF growth. Our findings provide novel insights into dynamic interplay between general and specific cognitive skills contributing to preschool maths.

Long-term cerebrovascular dysfunction in the offspring from maternal electronic cigarette use during pregnancy.

Electronic cigarettes (E-cigs) have been promoted as harm-free or less risky than smoking, even for women during pregnancy. These claims are made largely on E-cig aerosol having fewer number of toxic chemicals compared with cigarette smoke. Given that even low levels of smoking are found to produce adverse birth outcomes, we sought to test the hypothesis that vaping during pregnancy (with or without nicotine) would not be harm-free and would result in vascular dysfunction that would be evident in offspring during adolescent and/or adult life. Pregnant female Sprague Dawley rats were exposed to E-cig aerosol (1 h/day, 5 days/wk, starting on gestational day 2 until pups were weaned) using e-liquid with 0 mg/mL (E-cig0) or 18 mg/mL nicotine (E-cig18) and compared with ambient air-exposed controls. Body mass at birth and at weaning were not different between groups. Assessment of middle cerebral artery (MCA) reactivity revealed a 51%-56% reduction in endothelial-dependent dilation response to acetylcholine (ACh) for both E-cig0 and E-cig18 in 1-mo, 3-mo (adolescent), and 7-mo-old (adult) offspring (P < 0.05 compared with air, all time points). MCA responses to sodium nitroprusside (SNP) and myogenic tone were not different across groups, suggesting that endothelial-independent responses were not altered. The MCA vasoconstrictor response (5-hydroxytryptamine, 5-HT) was also not different across treatment and age groups. These data demonstrate that maternal vaping during pregnancy is not harm-free and confers significant cerebrovascular health risk/dysfunction to offspring that persists into adult life. NEW & NOTEWORTHY These data established that vaping electronic cigarettes during pregnancy, with or without nicotine, is not safe and confers significant risk potential to the cerebrovascular health of offspring in early and adult life. A key finding is that vaping without nicotine does not protect offspring from cerebrovascular dysfunction and results in the same level of cerebrovascular dysfunction (compared with maternal vaping with nicotine), indicating that the physical and/or chemical properties from the base solution (other than nicotine) are responsible for the cerebrovascular dysfunction that we observed. Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/maternal-vaping-impairs-vascular-function-in-theoffspring/.

Transradial Approach for Neuroendovascular Procedures: A Single-Center Review of Safety and Feasibility.

BACKGROUND AND PURPOSE: In recent years, the transradial approach has become more widely adopted for neuroendovascular procedures. The purpose of this study was to evaluate the safety and feasibility of a transradial approach and distal transradial access for neuroendovascular procedures in a single center. MATERIALS AND METHODS: Retrospective analysis was performed for all patients who underwent transradial approach or distal transradial access neuroendovascular procedures from January 2016 to August 2019 at a single center. Exclusion criteria included a Barbeau D waveform, a radial artery of <2 mm on sonographic evaluation, and known radial artery occlusion. Procedures were evaluated for technical success (defined as successful radial artery access and completion of the intended procedure without crossover to an auxiliary access site), complications, and adverse events during follow-up at 30 days. RESULTS: The transradial approach or distal transradial access was attempted in 279 consecutive patients (58.1% women; median age, 57.7 years) who underwent 328 standard or distal transradial approach procedures. Two-hundred seventy-nine transradial approach and 49 distal transradial approach procedures were performed (cerebral angiography [n = 213], intracranial intervention [n = 64], head and neck intervention [n = 30], and stroke intervention [n = 21]). Technical success was 92.1%. Immediate adverse events (2.1%) included radial access site hematoma (n = 5), radial artery occlusion (n = 1), and acute severe radial artery spasm (n = 1). Thirty-day adverse events (0.3%) included a radial artery pseudoaneurysm (n = 1). Twenty-six cases (7.9%) required crossover to transfemoral access. CONCLUSIONS: The transradial approach for neuroendovascular procedures is safe and feasible across a wide range of neuroendovascular interventions.

Investigation of fibrillin microfibrils in the canine cruciate ligament in dogs with different predispositions to ligament rupture.

Cranial cruciate ligament disease (CCLD) is the most common cause of pelvic limb lameness in dogs but its precise aetiopathogenesis is uncertain. Fibrillin microfibrils (FM) are complex macro-molecular assemblies found in many tissues including ligaments, where they are thought to play an important mechanical role. We hypothesised that FM ultrastructural variation correlates with the differing predisposition of canine breeds to CCLD. Non-diseased cranial and caudal cruciate ligaments (CCLs and CaCLs) were obtained from Greyhound (GH) and Staffordshire Bull Terrier (SBT) cadavers. Fibrillin microfibrils were extracted from the ligaments by bacterial collagenase digestion, purified by size-exclusion chromatography and subsequently visualized by atomic force microscopy (AFM). With AFM, FMs have a characteristic beads-on-a-string appearance. For each FM, periodicity (bead-bead distance) and length (number of beads/FM) was measured. Fibrillin microfibril length was found to be similar for GH and SBT, with non-significant inter-breed and inter-ligament differences. Fibrillin microfibril periodicity varied when comparing GH and SBT for CCL (GH 60.2 ± 1.4 nm; SBT 56.2 ± 0.8 nm) and CaCL (GH 55.5 ± 1.6 nm; SBT 61.2 ± 1.2 nm). A significant difference was found in the periodicity distribution when comparing CCL for both breeds (P < 0.00001), further, intra-breed differences in CCL vs CaCL were statistically significant within both breeds (P < 0.00001). The breed at low risk of CCLD exhibited a periodicity profile which may be suggestive of a repair and remodelling within the CCL.

Validation of the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) chronic kidney disease risk score in HIV-infected patients in the USA.

OBJECTIVES: The aim of the study was to assess the validity of an easy-to-calculate chronic kidney disease (CKD) risk score developed by the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) group in a longitudinal observational study of people living with HIV (PLWH) in the USA. METHODS: PLWH (2002-2016) without prior exposure to potentially nephrotoxic antiretroviral agents and with at least three estimated glomerular filtration rate (eGFR) test results were identified in the Observational Pharmaco-Epidemiology Research and Analysis (OPERA® ) cohort. Three samples were drawn independently using the same eligibility criteria but each using a different eGFR equation, specifically the Cockcroft-Gault (C-G), Modification of Diet in Renal Disease (MDRD) or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFR estimation method. Full and short D:A:D risk scores were applied. CKD was defined as a confirmed decrease in eGFR to < 60 mL/min/1.73 m2 (stages 3-5). Poisson models estimated the association between CKD incidence and a one-point increase in the continuous risk score. The incidence rate ratio (IRR), adjusted IRR (aIRR), and Harrell's discrimination statistic were used to assess validity. RESULTS: There were 19 444, 22 727 and 22 748 PLWH in the OPERA C-G, CKD-EPI and MDRD samples, respectively. The median (minimum-maximum) follow-up duration was 6.1 (0.3-9.1) years in the D:A:D cohort and ranged from 3.2 to 3.5 (0.2-15.5) years in the OPERA validation samples. The observation time for the majority of PLWH in the D:A:D cohort began prior to 2006, in stark contrast to the OPERA validation samples, where the majority of PLWH were observed after 2011. The CKD incidence ranged from 7.3 per 1000 person-years [95% confidence interval (CI) 6.8, 7.9 per 1000 person-years] in OPERA C-G to 11.0 (95% CI 10.4, 11.6 per 1000 person-years) in OPERA MDRD. In OPERA samples, IRRs by risk group and adjusted IRRs (full risk score) were similar to those in the D:A:D derivation cohort (adjusted IRR 1.3; 95% CI 1.3, 1.3). Harrell's c-statistic ranged from 0.87 to 0.92 in the OPERA samples, comparable to that in the derivation cohort (0.92). Results for short scores were similar. CONCLUSIONS: The findings support the validity of the D:A:D risk scoring method for assessing CKD (stages 3-5) probability in an exclusively USA-based sample regardless of eGFR method.

Comparison of Two Computational Methods for Estimating Transmissivity Based on the Picking Equation.

A comparison is presented of two computational methods, PICKINGmodel and PPC-Recovery, to estimate transmissivities based on the Picking equation using water-level recovery data from brief pumping tests of relatively low-yielding domestic wells. The tests were performed by the United States Geological Survey (USGS) in 50 domestic bedrock wells in south-central New York State, and USGS staff performed the analysis using PICKINGmodel based on the Picking equation. The results indicated that the estimated transmissivities ranged from 0.86 to 2900 ft2 /d (0.080 to 270 m2 /d) with a median of 41 ft2 /d (3.8 m2 /d). The same data were later analyzed using PPC-Recovery also based on the Picking equation. The two sets of estimated transmissivities were compared and statistically had the same median value at a probability of 95%. In another analysis, the PPC-Recovery method was applied to the same data that had been truncated at the point when the slope of the recovery data curve began to deviate from a straight line aligned with the middle portion of the recovery data. Comparing these resulting estimates of transmissivity with values originally obtained using the PICKINGmodel, the two had statistically the same median value for transmissivity at a probability of 95%. It was concluded that using PPC-Recovery in this manner to estimate transmissivity in low-yielding domestic wells will yield transmissivity values sufficiently close to the results had PICKINGmodel been used, and with less time and effort.

Direct determination of mode-projected electron-phonon coupling in the time domain.

Ultrafast spectroscopies have become an important tool for elucidating the microscopic description and dynamical properties of quantum materials. In particular, by tracking the dynamics of nonthermal electrons, a material's dominant scattering processes can be revealed. Here, we present a method for extracting the electron-phonon coupling strength in the time domain, using time- and angle-resolved photoemission spectroscopy (TR-ARPES). This method is demonstrated in graphite, where we investigate the dynamics of photoinjected electrons at the [Formula: see text] point, detecting quantized energy-loss processes that correspond to the emission of strongly coupled optical phonons. We show that the observed characteristic time scale for spectral weight transfer mediated by phonon-scattering processes allows for the direct quantitative extraction of electron-phonon matrix elements for specific modes.

First Measurement of the Total Neutron Cross Section on Argon between 100 and 800 MeV.

We report the first measurement of the neutron cross section on argon in the energy range of 100-800 MeV. The measurement was obtained with a 4.3-h exposure of the Mini-CAPTAIN detector to the WNR/LANSCE beam at LANL. The total cross section is measured from the attenuation coefficient of the neutron flux as it traverses the liquid argon volume. A set of 2631 candidate interactions is divided in bins of the neutron kinetic energy calculated from time-of-flight measurements. These interactions are reconstructed with custom-made algorithms specifically designed for the data in a time projection chamber the size of the Mini-CAPTAIN detector. The energy averaged cross section is 0.91±0.10(stat)±0.09(syst) b. A comparison of the measured cross section is made to the GEANT4 and FLUKA event generator packages, where the energy averaged cross sections in this range are 0.60 and 0.68 b, respectively.

Cavity-enhanced high harmonic generation for extreme ultraviolet time- and angle-resolved photoemission spectroscopy.

With its direct correspondence to electronic structure, angle-resolved photoemission spectroscopy (ARPES) is a ubiquitous tool for the study of solids. When extended to the temporal domain, time-resolved (TR)-ARPES offers the potential to move beyond equilibrium properties, exploring both the unoccupied electronic structure as well as its dynamical response under ultrafast perturbation. Historically, ultrafast extreme ultraviolet sources employing high-order harmonic generation (HHG) have required compromises that make it challenging to achieve a high energy resolution-which is highly desirable for many TR-ARPES studies-while producing high photon energies and a high photon flux. We address this challenge by performing HHG inside a femtosecond enhancement cavity, realizing a practical source for TR-ARPES that achieves a flux of over 1011 photons/s delivered to the sample, operates over a range of 8-40 eV with a repetition rate of 60 MHz. This source enables TR-ARPES studies with a temporal and energy resolution of 190 fs and 22 meV, respectively. To characterize the system, we perform ARPES measurements of polycrystalline Au and MoTe2, as well as TR-ARPES studies on graphite.

Shuttling a single charge across a one-dimensional array of silicon quantum dots.

Significant advances have been made towards fault-tolerant operation of silicon spin qubits, with single qubit fidelities exceeding 99.9%, several demonstrations of two-qubit gates based on exchange coupling, and the achievement of coherent single spin-photon coupling. Coupling arbitrary pairs of spatially separated qubits in a quantum register poses a significant challenge as most qubit systems are constrained to two dimensions with nearest neighbor connectivity. For spins in silicon, new methods for quantum state transfer should be developed to achieve connectivity beyond nearest-neighbor exchange. Here we demonstrate shuttling of a single electron across a linear array of nine series-coupled silicon quantum dots in ~50 ns via a series of pairwise interdot charge transfers. By constructing more complex pulse sequences we perform parallel shuttling of two and three electrons at a time through the array. These experiments demonstrate a scalable approach to physically transporting single electrons across large silicon quantum dot arrays.

Interactive effects of calcium and top-dressed 25-hydroxy vitamin D3 on egg production, egg shell quality, and bones attributes in aged Lohmann LSL-lite layers1.

Calcium and vitamin D are critical in attenuating metabolic Ca insufficiency often observed in older hens. We investigated interactive effects of dietary Ca and top-dressed 25-hydroxy vitamin D3 (25OHD3) on egg production, eggshell quality (thickness, EST, and breaking strength, ESBS), serum Ca, kidney, liver, and bones attributes in 74-wk old Lohmann LSL-lite layers. A total of 4 levels of Ca (3.0, 3.5, 4.0, and 4.5%) and 3 levels of 25OHD3 (0, 69, and 138 µg/kg) were tested. All diets had basal level of 3,300 IU of vitamin D3/kg, were allocated to 84 individually housed hens (n = 7), and fed to 81 wk of age. Dual-energy X-ray absorptiometry was used to measure bone mineral content (BMC) and density (BMD) in left ulna, femur, and tibia at week 74 (13 spare birds, baseline) and week 81. Birds fed diets containing 3.0, 3.5, 4.0, and 4.5% Ca consumed 3.4, 4.1, 4.2, and 4.8 Ca g/b/d. Interaction (P < 0.05) between Ca and 25OHD3 was such that 25OHD3 linearly increased egg weight and percentage of eggs graded as jumbo (≥70 g) at 3.0, 3.5, and 4.5% Ca levels. There was no interaction (P > 0.05) between Ca and 25OHD3 on the rest of the parameters. Calcium increased EST and ESBS quadratically (P < 0.05), EST increased with Ca intake up to 4.1 g of Ca/b/d whereas Ca intakes (3.4 and 4.8 g of Ca/b/d) had poor ESBS relative to intermediate Ca intakes. Kidney ash concentration increased linearly (P = 009) with Ca intake. However, BMC and BMD in ulna, tibia, and femur declined (P < 0.05) at week 81 relative to baseline. In conclusion, top dressed 25OHD3 linearly increased egg weight at various Ca intakes with no negative effect on eggshell quality or bone attributes. Feeding 4.1 to 4.2 g of Ca/b/d improved eggshell quality, however, higher intake deteriorated eggshell quality and increased renal ash accumulation with no benefit on skeletal integrity.