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We report on the observation of the circular transversal terahertz photoconductivity in monolayer graphene supplied by a back gate. The photoconductivity response is caused by the free carrier absorption and reverses its sign upon switching the radiation helicity. The observed dc Hall effect manifests the time inversion symmetry breaking induced by circularly polarized terahertz radiation in the absence of a magnetic field. For low gate voltages, the photosignal is found to be proportional to the radiation intensity and can be ascribed to the alignment of electron momenta by the combined action of THz and static electric fields as well as by the dynamic heating and cooling of the electron gas. Strikingly, at high gate voltages, we observe that the linear-in-intensity Hall photoconductivity vanishes; the photoresponse at low intensities becomes superlinear and varies with the square of the radiation intensity. We attribute this behavior to the interplay of the second- and fourth-order effects in the radiation electric field which has not been addressed theoretically so far and requires additional studies., 8 figures

We report on the observation of the ratchet effect -- generation of direct electric current in response to external terahertz (THz) radiation -- in bilayer graphene, where inversion symmetry is broken by an asymmetric dual-grating gate potential. As a central result, we demonstrate that at high temperature, $T = 150~\textrm{K}$, the ratchet current decreases at high frequencies as $ \propto 1/\omega^2$, while at low temperature, $T = 4.2~\textrm{K}$, the frequency dependence becomes much stronger $\propto 1/\omega^6$. The developed theory shows that the frequency dependence of the ratchet current is very sensitive to the ratio of the electron-impurity and electron-electron scattering rates. The theory predicts that the dependence $1/\omega^6$ is realized in the hydrodynamic regime, when electron-electron scattering dominates, while $1/\omega^2$ is specific for the drift-diffusion approximation. Therefore, our experimental observation of a very strong frequency dependence reveals the emergence of the hydrodynamic regime., Comment: 21 pages, 12 figures

The electrical insulation of the Megavolt ITER Injector and Concept Advancement (MITICA) beam source (BS) at 1 MV in vacuum is a challenging issue, which could not be fully addressed so far on the basis of experimental results and of theoretical models available in literature. A specific high-voltage (HV) test campaign is being prepared to validate and optimize the voltage holding capability of the BS insulation under realistic conditions, using full-size mockup electrodes reproducing in detail the geometry of the BS and accelerator. The proposed test strategy will address both the single-gap and the multistage insulation, so as to obtain a verification of voltage holding at 1 MV before the installation of the real components. This approach is intended to reduce the risk related to the HV insulation at 1 MV and, if necessary, to allow the development of effective corrections. In this article, the test motivations and requirements are defined, and the electrode implementation and diagnostic setup are described. Finally, the test configurations and the experimental procedure are discussed.

The detection of individual quanta of light is important for quantum computation, fluorescence lifetime imaging, single-molecule detection, remote sensing, correlation spectroscopy, and more. Thanks to their broadband operation, high detection efficiency, exceptional signal-to-noise ratio, and fast recovery times, superconducting nanowire single-photon detectors (SNSPDs) have become a critical component in these applications. The operation of SNSPDs based on conventional superconductors, which have a low critical temperature ($T_c$), requires costly and bulky cryocoolers. This motivated exploration of other superconducting materials with higher $T_c$ that would enable single-photon detection at elevated temperatures, yet this task has proven exceedingly difficult. Here we show that with proper processing, high-$T_c$ cuprate superconductors can meet this challenge. We fabricated superconducting nanowires (SNWs) out of thin flakes of Bi$_2$Sr$_2$CaCu$_2$O$_{8+\delta}$ and La$_{1.55}$Sr$_{0.45}$CuO$_4$/La$_2$CuO$_4$ (LSCO-LCO) bilayer films and demonstrated their single-photon response up to $25$ and $8$ K, respectively. The single-photon operation is revealed through the linear scaling of the photon count rate (PCR) on the radiation power. Both of our cuprate-based SNSPDs exhibited single-photon sensitivity at the technologically-important $1.5$ ${\mu}$m telecommunications wavelength. Our work expands the family of superconducting materials for SNSPD technology, opens the prospects of raising the temperature ceiling, and raises important questions about the underlying mechanisms of single-photon detection by unconventional superconductors., Comment: 8 pages, 3 figures

The purpose of this study is to show land use considering green infrastructure (GI) in a Japanese depopulated rural district. First, we classified six zones of the target area, depending on inundation risk, living environment, and area of each land use, by cluster analysis. As a result, we showed three characteristics of land use. These are the central built-up area with high disaster risk and high land price, the east side area with low disaster risk, and the paddy field area with high disaster risk. Next, we estimated the probability of vacant houses by logistic regression analysis. Based on the results and the six classified zones, we showed the area with high probability of vacant houses and high disaster risk. This area was observed at the central built-up area. Considering future depopulation, such a housing area in the central built-up area needs to shrink.

Van der Waals heterostructures comprised of two-dimensional (2D) materials offer a platform to obtain materials by design with unique electronic properties. Franckeite (Fr) is a naturally occurring van der Waals heterostructure comprised of two distinct alternately stacked semiconducting layers; (i) SnS$_2$ layer and (ii) Pb$_3$SbS$_4$. Though both layers in the heterostructure are semiconductors, the photoluminescence from Franckeite remains elusive. Here, we report the observation of photoluminescence (PL) from Franckeite for the first time. We observed two PL peaks at ~ 1.93 eV and ~ 2.11 eV. By varying the temperature from 1.5 K to 80 K, we found that the PL peak position redshifts and the integrated intensity decreases slowly as we increase the temperature. We observed linear dependence of photoluminescence integrated intensity on excitation laser power indicating that the photoluminescence is originating from free excitons in the SnS$_2$ layer of Fr. By comparing the PL from Fr with the PL from a monolayer MoS$_2$, we determined that the PL quantum efficiency from Fr is an order of magnitude lower than that of a monolayer MoS$_2$. Our study provides a fundamental understanding of the optical behavior in a complex naturally occurring van der Waals heterostructure, and may pave an avenue toward developing nanoscale optical and optoelectronic devices with tailored properties., Comment: 8 pages, 5 Figures, Accepted to Applied Physics Letter

In thermodynamic equilibrium, current in metallic systems is carried by electronic states near the Fermi energy whereas the filled bands underneath contribute little to conduction. Here we describe a very different regime in which carrier distribution in graphene and its superlattices is shifted so far from equilibrium that the filled bands start playing an essential role, leading to a critical-current behavior. The criticalities develop upon the velocity of electron flow reaching the Fermi velocity. Key signatures of the out-of-equilibrium state are current-voltage characteristics resembling those of superconductors, sharp peaks in differential resistance, sign reversal of the Hall effect, and a marked anomaly caused by the Schwinger-like production of hot electron-hole plasma. The observed behavior is expected to be common for all graphene-based superlattices., Comment: 22 pages, 11 figures

Hole-conjugate states of the fractional quantum Hall effect host counter-propagating edge channels which are thought to exchange charge and energy. These exchanges have been the subject of extensive theoretical and experimental works; in particular, it is yet unclear if the presence of integer quantum Hall edge channels stemming from fully filled Landau levels affects heat equilibration along the edge. In this letter, we present heat transport measurements in quantum Hall states of graphene demonstrating that the integer channels can strongly equilibrate with the fractional ones, leading to markedly different regimes of quantized heat transport that depend on edge electrostatics. Our results allow for a better comprehension of the complex edge physics in the fractional quantum Hall regime., Comment: Includes supplemental material

Background An important therapeutic aim in ulcerative colitis (UC) is endoscopic remission. Although an endoscopic score with white light imaging (WLI) is mainly used to evaluate endoscopic findings, recently, the usefulness of linked color imaging (LCI) has been reported. We evaluated the relationship between LCI and histopathological findings and attempted to establish a new LCI endoscopic evaluation index for UC. Methods This study was conducted at Kyorin University, Kyoto Prefectural University, and Fukuoka University Chikushi Hospital. Ninety-two patients (median age, 46 years; male/female ratio, 48/34) with a Mayo endoscopic subscore (MES) ≤1 who underwent colonoscopy for UC in clinical remission between November 2016 and January 2019 were included. LCI index was defined as degree of redness (R) (grade 0–2), area of inflammation (A) (grade 0–3), and visibility of lymphoid follicles (L) (grade 0–3). Endoscopic scores were determined by three central endoscopic judgment committee members who are experts in colonoscopy for UC. Discussions were held among the three members, and when two or more of them had the same judgment this was adopted as the final evaluation. Each biopsy was performed from an identical site of colonoscopic image. Histological healing was defined as Geboes score Results In 92 patients, 85 biopsies from the sigmoid colon and 84 biopsies from the rectum (total 169 biopsies) were evaluated. Percentage of judgments that were consistent in two or more central endoscopic judgment committee members were 167/169 (98.8%) cases in MES, 164/169 (97.0%) cases in LCI index-R, 152/169 (89.9%) cases in LCI-index-A, and 150/169 (88.8%) cases in LCI-index-L. Regarding the κ-score in diagnosing by the two pathologists, "Chronic inflammatory infiltrate", "Crypt destruction", and "Crypt destruction" had a moderate agreement, and others had a stationary agreement. The overall histological healing rate was 84.0% (142/169). There were 22/117/30 cases of grade 0/1/2 in LCI index-R, 113/34/17/5 cases of grade 0/1/2/3 in LCI index-A, and 124/27/14/4 cases of grade 0/1/2/3 in LCI index-L. Histological healing was achieved in 84.1% (142/169) of the cases, and there were significant associations with histological healing/non-healing in LCI index-R (P=0.013) and A (P=0.0014). Conclusion A new LCI index is useful for predicting histological healing in UC patients with MES ≤1 and clinical remission.

We employ dual-gated 30{\deg}-twisted bilayer graphene to demonstrate simultaneous ultra-high mobility and conductivity (up to 40 mS at room temperature), unattainable in a single-layer of graphene. We find quantitative agreement with a simple phenomenology of parallel conduction between two pristine graphene sheets, with a gate-controlled carrier distribution. Based on the parallel transport mechanism, we then introduce a method for in situ measurements of the chemical potential of the two layers. This twist-enabled approach, neither requiring a dielectric spacer, nor separate contacting, has the potential to greatly simplify the measurement of thermodynamic quantities in graphene-based systems of high current interest., Comment: This is the unedited authors' version of the submitted article, published in Phys. Rev. B 104, L241410 (2021), 23 pages, main text and supplementary information

International audience; We present magneto-photoluminescence measurements in a hybrid 2D semiconductor/ ferromagnetic structure consisting of MoSe2/hBN/Ni. When the Nickel layer is magnetized, we observe circularly polarized photoluminescence of the trion peak in MoSe2 monolayer under linearly polarized excitation. This build-up of circular polarization can reach a measured value of about 4% when the magnetization of Ni is saturated perpendicularly to the sample plane, and changes its sign when the magnetization is reversed. The circular polarization decreases when the hBN barrier thickness increases. These results are interpreted in terms of a spin-dependent charge transfer between the MoSe2 monolayer and the Nickel film. The build-up of circular polarization is observed up to 120 K, mainly limited by the trion emission that vanishes with temperature.

Dielectric engineering of heterostructures made from two-dimensional van der Waals semiconductors is a unique and powerful tool to tailor the electric and optical band gaps solely via the dielectric environment and the crystal thickness modulation. Here, we utilize high quality MoTe2 monolayer and bilayer crystals as a candidate for near-infrared photonic applications. The crystals are exfoliated on various technologically relevant carrier substrates: silicon/silicon dioxide, poly(methyl methacrylate), hexagonal boron nitride, silicon carbide, and silicon nitride. These substrates provide a large range of high frequency dielectric constants from 2.1 to 7.0 for MoTe2-containing heterostructures. We assess the relationship between the environmental dielectric function and Coulomb screening by combining detailed spectroscopic measurements, utilizing low-temperature and high-spatially resolved photoluminescence and contrast reflectivity, with microscopic many-body modeling, to explore the potential of this less-recognized material platform for applications in optoelectronics at photon wavelengths above 1 μm. We observe a redshift of the optical gap emission energy from the monolayer to bilayer regime on the order of 30 meV. Furthermore, the thickness controlled shift is slightly larger than the one induced by the local dielectric environment, which ranges on the order of 20 meV for the MoTe2 monolayers and on the order of 8 meV for the MoTe2 bilayers. We also show that the local dielectric screening barely affects the trion binding energy, which is captured by our microscopic model, accounting for the screened Coulomb potential for the heterostructures.

BL-774 is a control, data acquisition, and online analysis platform for addressing the requirements in future beamline experiments at SPring-8-II. To date, we have achieved implementations related to “robustness and flexibility” and “configuration management”. These implementations were made possible by the two-phase development workflow. The two-phase development is characterized by a dedicated rapid application development environment that beamline scientists can use rapidly and easily in real beamline environments, and web-based graphical user interfaces that BL-774 software developers have incorporated the achievements of the beamline scientists as part of the official release of the beamline control software. BL-774 has been introduced in two beamlines to date, and we plan to implement it in more beamlines while adding more features. We plan to integrate BL-774 seamlessly with other systems that are currently under development in the facility, such as two-dimensional detector systems and SPring-8 data centers. By introducing BL-774 in conjunction with other infrastructure in the facility, more advanced experimental operations, such as feedback operations based on online data analysis or remote operations from outside the beamlines, are to be expected. This paper presents the design and implementation of BL-774 and its introduction into a beamline at SPring-8.

Even though charge transport in semiconducting polymers is of relevance for a number of potential applications in (opto-)electronic devices, the fundamental mechanism of how charges are transported through organic polymers that are typically characterized by a complex nanostructure is still open. One of the challenges which we address here, is how to gain controllable experimental access to charge transport at the sub-100 nm lengthscale. To this end charge transport in single poly(diketopyrrolopyrrole-terthiophene) fiber transistors, employing two different solid gate dielectrics, a hybrid Al2O3/self-assembled monolayer and hexagonal boron nitride, is investigated in the sub-50 nm regime using electron-beam contact patterning. The electrical characteristics exhibit near ideal behavior at room temperature which demonstrates the general feasibility of the nanoscale contacting approach, even though the channels are only a few nanometers in width. At low temperatures, we observe nonlinear behavior in the current–voltage characteristics in the form of Coulomb diamonds which can be explained by the formation of an array of multiple quantum dots at cryogenic temperatures.

Electrical resistance usually originates from lattice imperfections. However, even a perfect lattice has a fundamental resistance limit, given by the Landauer

Bonding of Indium phosphide (InP)-based electronic device and Silicon Carbide (SiC) heat spreader is beneficial to thermal management. In this study, InP/SiC structure was demonstrated using surface activated direct bonding at room temperature. The bond quality was evaluated by dicing testing and tensile testing.

Background Percutaneous coronary intervention (PCI) for calcified coronary artery remains challenging in the drug-eluting stent (DES) era. The effectiveness of drug-coated balloons (DCBs) and orbital atherectomy system (OAS) is unknown. Methods In this retrospective, single-center study, we compared the use of DCBs with second- and third-generation DESs following orbital atherectomy (OA) for calcified de novo coronary lesions. All patients underwent PCI with intravascular imaging. The primary endpoint was major cardiac event, that was a composite of cardiac death, death for unknown cause, non-fatal myocardial infarction, or target lesion revascularization at 1 year. Results Between June 2018 and December 2019, 107 patients with coronary lesions were enrolled in this study and divided into two groups: 23 patients in DCB group and 84 patients in DES group. The post-procedure segment percentage diameter stenosis was 23.1% (interquartile range [IQR], 17.7 to 32.5) with DCB versus 14.4% (IQR, 10.0 to 21.2) with DES (P Conclusions In calcified coronary artery disease, using DCB following OA is as safe and effective as using DES following OA with respect to 1-year clinical outcomes. Funding Acknowledgement Type of funding sources: None.

Background It has been reported that decreased nitric oxide bioavailability due to increased reactive oxygen species (ROS) is one of the most important causes of coronary artery spasm (CAS). Xanthine oxidoreductase (XOR) is the rate-limiting enzyme for uric acid (UA) production and plays a pivotal role in generating ROS. It was reported that the gender differences exist in the impact of serum UA levels on cardiovascular risks. We previously demonstrated that increased plasma XOR activity is significantly associated with the incidence of CAS. However, the gender differences in the impact of plasma XOR activity on CAS remain unclear. Purpose The aim of this study was to examine the gender differences in the clinical impact of plasma XOR activity on CAS. Methods We investigated plasma XOR activity in 132 patients suspected for CAS (male, n=78; female, n=54), and underwent intracoronary acetylcholine provocation test. XOR activity assay was performed using stable isotope-labeled substrate and liquid chromatography-triple quadrupole mass spectrometry. Provoked CAS was defined as total or subtotal occlusion (≥90%) with accompanying symptoms of chest pain and/or ischemic ST-segment changes on the electrocardiogram. We excluded the patients who had significant coronary artery stenosis (≥50%) and/or were taking XOR inhibitors. Results Plasma XOR activity was significantly lower in female compared with male patients (30.3 pmol/h/mL, interquartile range (IQR) 22.8–42.7 vs. 51.7 pmol/h/mL, IQR 34.7–101.8; P Conclusions Plasma XOR activity was an independent predictor for the incidence of CAS in both genders. The impact of plasma XOR activity on CAS was stronger in female patients than in male patients. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

The Agulhas Current (AC) off the southern tip of Africa is one of the strongest western boundary currents and a crucial chokepoint of inter-ocean heat and salt exchange between the Indian and the South Atlantic Ocean. However, large uncertainties remain concerning the sea surface temperature and salinity variability in the AC region and their driving mechanisms over longer time scales, due to short observational datasets and the highly dynamic nature of the region. Here, we present an annual coral skeletal Sr/Ca composite record paired with an established composite oxygen isotope record from Ifaty and Tulear reefs in southwestern Madagascar to obtain a 334 year-long (1661–1995) reconstruction ofδ18Oseawater changes related to surface salinity variability in the wider Agulhas Current region. Our new annual δ18Oseawater composite record from Ifaty traces surface salinity of the southern Mozambique Channel and AC core region from the SODA reanalysis since 1958. δ18Oseawater appears mainly driven by large-scale wind forcing in the southern Indian Ocean on interannual to decadal time scales. The δ18Oseawater and SST at Ifaty show characteristic interannual variability of between 2 to 4 years, typical for ENSO. Lagged correlations with the Multivariate ENSO index reveals a 1–2 year lag of δ18Oseawater and salinity at Ifaty and the AC region, suggesting that propagation of anomalies by ocean Rossby waves may contribute to salinity changes in the wider southwestern Indian Ocean. The δ18Oseawater and SST reconstructions at Ifaty reveal the highest interannual variability during the Little Ice Age, especially around 1700, which is in agreement with other Indo-Pacific coral studies. Our study demonstrates the huge potential to unlock past interannual and decadal changes in surface ocean hydrology and ocean transport dynamics from coral δ18Oseawater beyond the short instrumental record.

This brief report summarizes the comparative experience of an inpatient rehabilitation facility dealing with two episodes of COVID-19 infection, one before and one after the availability of vaccination, which was deployed to staff. The experience exemplifies the high rate of infection and potential for asymptomatic presentation of COVID-19 as well as the protective advantage of the vaccine for healthcare workers in this report. With a significant reduction in the rate of infection, from nearly 30% before vaccination to only 2.5% after vaccination. The data presented should serve as an encouragement for vaccination across all populations.

We demonstrate that optically active emitters can be locally generated by focusing a He-ion beam onto monolayer WS2 encapsulated in hBN. The emitters show a low-temperature photoluminescence spectrum, which is well described by an independent Boson model for localized emitters. Consistently, the photoluminescence intensity of the emitters saturates at low excitation intensities, which is distinct to the photoluminescence of excitonic transitions in the investigated WS2 monolayers. The demonstrated method allows us to position defect emitters in WS2 monolayers on demand. A statistical analysis suggests the generation yield of individual emitters to be as high as 11% at the highest investigated He-ion doses.

BackgroundDenosumab, a human IgG2 monoclonal antibody with high affinity for RANKL, is approved for treatment of bone erosion (ER) in patients with RA, based on the results of clinical trials. However, its effectiveness in combination with conventional therapy in RA patients has not been fully investigated in clinical practice.ObjectivesThis exploratory study aimed to compare, in patients receiving conventional synthetic disease-modifying anti-rheumatic drugs (csDMARD) for treatment of RA, the effectiveness of combined use of csDMARD and denosumab vs csDMARD alone, in terms of inhibition of ER determined by HR-pQCT.MethodsDetail protocol of this open-label, randomized, parallel-group study has been published previously.1 RA patients with moderate or low disease activity and progressive ER were eligible, and were randomly assigned to receive denosumab in addition to the csDMARD (denosumab) group or to continued use of the csDMARD alone (csDMARD) group. Denosumab was administered every 6 months during the 12-month study period. The primary endpoint was change in ER-depth at the second and third metacarpal bones, determined by HR-pQCT at month 6. For the primary endpoint, a linear mixed effect model analysis was performed using treatment group, sex, anti-cyclic citrullinated peptide (CCP) antibody (positive vs negative), and baseline disease activity (DAS28-ESR) as fixed effects, patients as random effects, and baseline values as covariates. For extension data, measurement time-point and the interaction between treatment group and measurement time-point was further added as fixed effects. The adverse events (AEs) were recorded.ResultsA total of 46 patients were randomized to denosumab and csDMARD groups (both N=23), and baseline characteristics were similar between both groups. Although the difference was not significant, the estimate mean (95%CI) change of ER-depth at month 6 from baseline as the primary endpoint was −0.57 (−1.52, 0.39) in the denosumab group vs −0.22 (−0.97, 0.53) in the csDMARD group, respectively. At months 6 and 12, ER-depth, -width, and -volume (extension data) were numerically lower in the denosumab group than in the csDMARD group (Table 1). Compared with patients in the csDMARD group, those in the denosumab group had significantly higher volumetric bone mineral density (vBMD) at month 12. AEs were reported in 12 (52.2%) and 13 (56.5%) of patients in the denosumab and csDMARD groups, respectively. The most common AEs of denosumab groups was hypocalcemia (reported in 4), and all the events were causally related with denosumab. Serious AEs were reported in 1 (4.3%) and 2 (8.7%) of patients in the denosumab and csDMARD groups, and which were not related to treatment drug.Table 1.ER and microstructure in denosumab group vs csDMARD groupMonthDenosumab group (n=21)csDMARDs group (n=22)Difference (Denosumab- csDMARDs)n1Estimate Means [95%CI]n1Estimate Means [95%CI]Estimate Means [95%CI]ER-depth617−0.46 [−1.31, 0.39]25−0.20 [−0.89, 0.49]−0.27 [−0.86, 0.32]1217−0.56 [−1.41, 0.29]22−0.20 [−0.90, 0.49]−0.35 [−0.95, 0.24]ER-width617−0.26 [−1.10, 0.57]25−0.06 [−0.73, 0.61]−0.20 [−0.81, 0.40]1217−0.27 [−1.10, 0.56]22−0.03 [−0.70, 0.64]−0.24 [−0.85, 0.38]ER-volume616−6.21 [−23.89, 11.46]24−1.71 [−16.07, 12.66]−4.51 [−16.67, 7.65]1217−6.25 [−23.94, 11.44]21−3.18 [−17.56, 11.20]−3.07 [−15.32, 9.17]vBMD6426.41 [2.78, 10.03]442.46 [−1.33, 6.24]3.95 [−0.05, 7.94]12389.20 [5.46, 12.95]423.66 [−0.15, 7.46]5.55 [1.46, 9.63]*These were extension data.This is the efficacy analysis set which excluded 3 patients from the full analysis set.*; pn, number of patients; n1, number of measurement pointsConclusionOur results suggest that adding denosumab to csDMARD therapy may help prevent ER, promote ER repair, and improve bone microstructure.References[1]Iwamoto N, et al., Trials. 2019;20(1):1–8.Disclosure of InterestsNaoki Iwamoto Speakers bureau: Daiichi Sankyo Co., Ltd., Grant/research support from: Daiichi Sankyo Co., Ltd., Ko Chiba Speakers bureau: Daiichi Sankyo Co., Ltd., Shuntaro Sato: None declared, Kazuteru Shiraishi: None declared, Konosuke Watanabe: None declared, Nozomi Ohki: None declared, Akitomo Okada: None declared, Tomohiro Koga: None declared, Makiko Kobayashi Employee of: Daiichi Sankyo Co., Ltd. (retired at submission), Kengo Saito Employee of: Daiichi Sankyo Co., Ltd., Naoki Okubo Employee of: Daiichi Sankyo Co., Ltd., Atsushi Kawakami Speakers bureau: Daiichi Sankyo Co., Ltd., Grant/research support from: Daiichi Sankyo Co., Ltd.

Nonequilibrium dynamics of strongly correlated systems constitutes a fascinating problem of condensed matter physics with many open questions. Here, we investigate the relaxation dynamics of Landau-quantized electron system into spin-valley polarized ground state in a gate-tunable MoSe_{2} monolayer subjected to a strong magnetic field. The system is driven out of equilibrium with optically injected excitons that depolarize the electron spins and the subsequent electron spin-valley relaxation is probed in time-resolved experiments. We demonstrate that both the relaxation and light-induced depolarization rates at millikelvin temperatures sensitively depend on the Landau level filling factor: the relaxation is enhanced whenever the electrons form an integer quantum Hall liquid and slows down appreciably at noninteger fillings, while the depolarization rate exhibits an opposite behavior. Our findings suggest that spin-valley dynamics may be used as a tool to investigate the interplay between the effects of disorder and strong interactions in the electronic ground state.

Background IBD patients on immune-modulatory therapies are considered high-risk for SARS-CoV-2 infection. Direct comparisons of serological responses to SARS-CoV-2 infection in IBD patients across different continents and medications are lacking. We performed SARS-CoV-2 sero-surveillance of IBD patients prior to vaccination at seven large tertiary centres in Asia, Europe, and North America. Methods Clinical data and sera were collected from, 2,213 IBD patients receiving routine care at institutions in Belgium, Canada, Hong Kong, India, Japan, the United Kingdom, and the United States between, 26 May, 2020 and, 24 September, 2021 (Table, 1). Sera were taken prior to vaccination. Clinical data were collected through patient questionnaires and medical records. Antibody reactivity to the SARS-CoV-2 spike protein was assessed using the Roche SARS-CoV-2 anti-spike total antibody and/or Siemens Healthineers COV2T anti-spike total antibody assays, which showed, 99.4% concordance. Univariate analysis was performed to evaluate association between individual variables and sero-status. Results The pre-vaccination seroprevalence of antibodies to SARS-CoV-2 in IBD patient varied widely according to location from, 0% in Hong Kong to, 57.9% in New Delhi, India (p Conclusion We confirm in diverse poulations that exposure to biologics or immunomodulators, type of disease, and smoking status are associated with seroprevalence and antibody levels. We show for the first time the dominant influence of geographical location on sero-status in these patients. These observations should be considered as we look towards post-vaccination data to help stratify patients for clinical guidelines on SARS-CoV-2 vaccination.

Background Patients with complex Crohn’s perianal fistulas were treated with allogenic mesenchymal stem cells (darvadstrocel) in pivotal studies, and in clinical practice in Europe since, 2018. However, it is unclear whether the same efficacy and safety could be expected across different ethnic groups. Moreover, it is known that perianal complications including perianal fistulas are more frequent in Asian patients with Crohn’s disease (CD). Methods Japanese adult patients with treatment-refractory complex perianal fistulas in CD were enrolled from, 9 sites in a phase, 3, open-label, single-arm, uncontrolled study. Patients could have, 2 internal and, 3 external openings at maximum, and their luminal disease was non-active or mildly active (CDAI ≤220) at baseline. A single dose (24mL, 120 million cells) of darvadstrocel was intralesionally injected, and results after, 24 and, 52 weeks were evaluated. Primary endpoint was combined remission (a remission rate evaluated clinically and by MRI) at Week 24. Results 22 patients (mean age, 36.4 years, 63.6% male, mean duration of CD, 11.3 years) were enrolled. A half (11/22) had, 1 internal opening (IO) and, 2 external openings (EO) followed by, 1IO-1EO/2IO-2EO/2IO-3EO (3 each, 9/22) and, 1IO-3EO (2/22)., 59.1% and, 68.2% achieved combined remission at Week, 24 (primary endpoint) and Week, 52, respectively. Up to Week, 52, 90.9% (20/22) experienced adverse events (AE), and, 81.8% (18/22) were mild or moderate in intensity. Proctalgia (6/22), nasopharyngitis (5/22), and anal fistula (4/22) were most frequently reported. There was no death or AE-related study discontinuation. Conclusion 52 weeks after administrating darvadstrocel in Japanese patients with complex perianal fistulas in CD, fistula closure was confirmed in, 68% (15/22) and partial closure in, 90.0% (20/22). These findings are consistent with the pivotal study ADMIRE-CD, and real-world case-series reported from Europe. Furthermore, no new safety concerns were identified.

The Akkadian Empire was the first united empire in Mesopotamia and was established at 4.6 kyr B.P. (where present is A.D. 1950). The empire abruptly collapsed in 4.2 ± 0.2 kyr B.P. Seasonal-scale climatic dynamics behind this collapse have not yet been resolved. Here, we present monthly climatic parameters (temperature and hydrology) inferred from fossil Omani corals that lived between 4.5 and 2.9 kyr B.P. Winter temperatures derived from a modern Omani coral correlate with winter shamal (western Asian dust storm) frequency. A fossil coral from 4.1 kyr B.P. shows a prolonged winter shamal season with frequent shamal days. This likely caused agricultural failures in Mesopotamia and contributed to the Akkadian Empire collapse, as this region depends on winter rainfall.

Mutations in KEAP1 and NFE2L2 (encoding the protein Nrf2) are prevalent in both adeno and squamous subtypes of non–small cell lung cancer, as well as additional tumor indications. The consequence of these mutations is stabilized Nrf2 and chronic induction of a battery of Nrf2 target genes. We show that knockdown of Nrf2 caused modest growth inhibition of cells growing in two-dimension, which was more pronounced in cell lines expressing mutant KEAP1. In contrast, Nrf2 knockdown caused almost complete regression of established KEAP1-mutant tumors in mice, with little effect on wild-type (WT) KEAP1 tumors. The strong dependency on Nrf2 could be recapitulated in certain anchorage-independent growth environments and was not prevented by excess extracellular glutathione. A CRISPR screen was used to investigate the mechanism(s) underlying this dependence. We identified alternative pathways critical for Nrf2-dependent growth in KEAP1-mutant cell lines, including the redox proteins thioredoxin and peroxiredoxin, as well as the growth factor receptors IGF1R and ERBB3. IGF1R inhibition was effective in KEAP1-mutant cells compared with WT, especially under conditions of anchorage-independent growth. These results point to addiction of KEAP1-mutant tumor cells to Nrf2 and suggest that inhibition of Nrf2 or discrete druggable Nrf2 target genes such as IGF1R could be an effective therapeutic strategy for disabling these tumors. Significance: This study identifies pathways activated by Nrf2 that are important for the proliferation and tumorigenicity of KEAP1-mutant non–small cell lung cancer.

This paper reports the first CMOS RF integrated chipset for secure commercial and military satellite communication enabling next-generation low size, weight, and power (SWaP) terminals. This chipset is a significant departure from current terminals relying on individually qualified IC components by taking advantage of advanced CMOS integration. The transmitter and receiver designs are digital IF architectures that rely on the higher sampling rate capability of CMOS, and precise digital filtering, quadrature frequency translation, and frequency hopping/de-hopping. The CMOS transmitter is a fully integrated system-on-chip (SoC) design, while the receiver consists of a co-designed RF and digital IF receiver. The Tx/Rx uses a 200-/300-MHz double data rate (DDR) interface driving/receiving a complex frequency translator with sub-hertz frequency hopping resolution via on-chip numerically controlled oscillators (NCO). The transmitter includes two 12-b return-to-zero (RZ) digital-to-analog converters (DACs) and quadrature modulator to form a single-sideband (SSB) upconverter achieving >30-dB spur rejection. An RF upconverter with an X2 multiplier drives a 24-dBm $Q$ -band CMOS stacked power amplifier (PA). The RF receiver implements a matched inverter amplifier (IA) followed by a complementary active balun that current drives a passive mixer with a trans-impedance active combiner. The digital IF receiver includes a high-linearity variable gain amplifier (VGA) that drives an 8 $\times $ time-interleaved 1.2-GS/s analog-to-digital converter (ADC) with dc offset and gain calibration with an embedded digital receiver. Both the transmitter and receiver use a 1.5-GHz IF signal. The combined CMOS chipset was demonstrated with a current military satcom modulation and protocol and achieves 5 $\times $ lower power consumption and size versus the current configuration.

Van der Waals layered materials with well-defined twist angles between the crystal lattices of individual layers have attracted increasing attention due to the emergence of unexpected material properties. As many properties critically depend on the exact twist angle and its spatial homogeneity, there is a need for a fast and non-invasive characterization technique of the local twist angle, to be applied preferably right after stacking. We demonstrate that confocal Raman spectroscopy can be utilized to spatially map the twist angle in stacked bilayer graphene for angles between 6.5{\deg} and 8{\deg} when using a green excitation laser. The twist angles can directly be extracted from the moir\'e superlattice-activated Raman scattering process of the transverse acoustic (TA) phonon mode. Furthermore, we show that the width of the TA Raman peak contains valuable information on spatial twist angle variations on length scales below the laser spot size of ~ 500 nm., Comment: 14 pages, 10 figures

Recently hBN has become an interesting platform for quantum optics due to the peculiar defect-related luminescence properties. Concomitantly, hBN was established as the ideal insulating support for realizing 2D materials device, where, on the contrary, defects can affect the device performance. In this work, we study the light emission properties of hBN flakes obtained by mechanical exfoliation with particular focus on extended defects generated in the process. In particular, we tackle different issues as the light emission in hBN flakes of different thicknesses in the range of hundreds of nm, revealing a higher concentration of deep level emission in thinner area of the flake. We recognize the effect of crystal deformation in some areas of the flake with an important blue-shift (130 meV) of the room temperature near band edge emission of hBN and the concurrent presence of a novel emission at 2.36 eV related to the formation of array of dislocations. We studied the light emission properties by means of cathodoluminescence and sub-bandgap excitation photoluminescence of thickness steps with different crystallographic orientations, revealing the presence of different concentration of radiative centers. CL mapping allows to detect buried thickness steps, invisible to the SEM and AFM morphological analysis., 27 pages, 6 figures, 1 table

In view of the extensive use of hexagonal boron nitride (hBN) in 2D material electronics, it becomes important to refine its dielectric characterization in terms of low-field permittivity and high-field strength and conductivity up to the breakdown voltage. The present study aims at filling this gap using DC and RF transport in two Au-hBN-Au capacitor series of variable thickness in the 10--100 nm range, made of large high-pressure, high-temperature (HPHT) crystals and a polymer derivative ceramics (PDC) crystals. We deduce an out-of-plane low field dielectric constant $\epsilon_\parallel=3.4\pm0.2$ consistent with the theoretical prediction of Ohba et al., that narrows down the generally accepted window $\epsilon_\parallel=3$--$4$. The DC-current leakage at high-field is found to obey the Frenkel-Pool law for thermally-activated trap-assisted electron transport with a dynamic dielectric constant $\epsilon_\parallel\simeq3.1$ and a trap energy $\Phi_B\simeq1.3\;\mathrm{eV}$, that is comparable with standard technologically relevant dielectrics., Comment: 10 pages, 2 figures, AM version in Materials Research Express

The baseline sagittal vertical axis (SVA) and pelvic tilt (PT) are independent risk factors of osteoporosis-related fractures in women with osteoporosis. We clarified the SVA and PT to predict the incidence of osteoporosis-related fractures.Sagittal alignment with osteoporosis women deteriorates with advancing age and sagittal alignment may indicate osteoporosis-related fractures in the future. However, whether the sagittal alignment predicts future osteoporosis-related fracture in patients with osteoporosis has not been clarified. We aimed to investigate the association between sagittal alignment and future osteoporosis-related fractures.This was a retrospective cohort study. Of the 313 participants (mean follow-up period, 2.9 years), 236 were included in the analysis. At baseline, we measured bone mineral density (BMD) of the lumbar spine and the femoral neck, sagittal vertical axis (SVA), thoracic kyphosis, pelvic incidence minus lumbar lordosis, sacral slope, pelvic tilt (PT), geriatric locomotive function scale (GLFS), two-step value, and stand-up test. The information on medications and the duration of treatment were reviewed from the medical records. Additionally, participants reported their history of falls at baseline. Multiple logistic regression analysis was used to determine the association of future osteoporosis-related fracture, and adjusted Odds ratios (OR) and 95% confidence interval (CI) were calculated with all predictors as covariates. All continuous variables were calculated using standardized OR (sOR).Osteoporosis-related fractures occurred in 33 of 313 participants (10.5%). Multiple logistic regression analysis showed that a history of falls (OR =4.092, 95% CI: 1.029-16.265, p =0.045), SVA (sOR =4.228, 95% CI: 2.118-8.439, p0.001), and PT (sOR =2.497, 95% CI: 1.087-5.733, p =0.031) were independent risk factors for future osteoporosis-related fractures.This study revealed the SVA and PT to predict osteoporosis-related fractures.UMIN000036516 (April 1, 2019).