Search

Cys2His2 zinc finger (ZF) domains engineered to bind specific target sequences in the genome provide an effective strategy for programmable regulation of gene expression, with many potential therapeutic applications. However, the structurally intricate engagement of ZF domains with DNA has made their design challenging. Here we describe the screening of 49 billion protein–DNA interactions and the development of a deep-learning model, ZFDesign, that solves ZF design for any genomic target. ZFDesign is a modern machine learning method that models global and target-specific differences induced by a range of library environments and specifically takes into account compatibility of neighboring fingers using a novel hierarchical transformer architecture. We demonstrate the versatility of designed ZFs as nucleases as well as activators and repressors by seamless reprogramming of human transcription factors. These factors could be used to upregulate an allele of haploinsufficiency, downregulate a gain-of-function mutation or test the consequence of regulation of a single gene as opposed to the many genes that a transcription factor would normally influence.

Objectives The aim of this AFIRE (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease) trial subgroup analysis was to examine rivaroxaban monotherapy benefits and their relation to the time between stenting and enrollment among patients after coronary stenting. Background Of 2,215 patients with atrial fibrillation and stable coronary artery disease in the AFIRE trial, rivaroxaban monotherapy was noninferior to rivaroxaban plus antiplatelet therapy (combination therapy) in terms of efficacy and superior for safety endpoints. However, thrombotic risk after antiplatelet therapy cessation remained a concern among 1,444 patients who had undergone coronary stenting >1 year before enrollment. Methods The benefits of rivaroxaban monotherapy in coronary stenting subgroups were assessed for efficacy (a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or death of any cause), safety (major bleeding defined according to International Society on Thrombosis and Haemostasis criteria), ischemic endpoints, net adverse clinical event, and time between stenting and enrollment. Results Efficacy and safety endpoints for monotherapy were superior to combination therapy, with HRs of 0.70 for efficacy (95% CI: 0.50-0.98; P = 0.036) and 0.55 for safety (95% CI: 0.33-0.92; P = 0.019). For ischemic endpoints, the HR was 0.82 (95% CI: 0.58-1.15; P = 0.240). The HR became smaller with longer time between stenting and enrollment (efficacy, P for interaction = 0.158; safety, P = 0.097). Conclusions In patients with atrial fibrillation after coronary stenting, the benefits of rivaroxaban monotherapy for efficacy and safety endpoints were consistent with those in the whole AFIRE trial population. The benefits became apparent with longer time between stenting and enrollment. (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease Study [AFIRE]; UMIN000016612 , NCT02642419 )

Ξ− atomic X-ray spectroscopy is one of the most useful methods for investigation of the Ξ–nucleus strong interaction. Since the X-ray energy is shifted and/or broadened due to the Ξ–nucleus strong interaction compared to those calculated from electromagnetic interaction alone, the measurement of the energy shift, ΔE, and the width, Γ, give us information on the Ξ–nucleus potential. A serious problem in the measurement is the significant background derived from in-flight Ξ− decay. A novel method of identifying stopped Ξ− events using the nuclear emulsion was developed to realize the first Ξ− atomic X-ray spectroscopy experiment as the J-PARC E07 experiment, which also aimed at searching for ΛΛ and Ξ− hypernuclei in the emulsion. The X-rays emitted from Ξ− Br and Ξ− Ag atoms were measured using germanium detectors. No clear peaks were observed in the obtained spectra. However, we succeeded in reducing the background to 1/170 by this method employing coincidence measurements using nuclear emulsion and X-ray detectors.

J-PARC E16 is an experiment to examine the origin of hadron mass through a systematic measurement of spectral changes of vector mesons in nuclei. The measurement of $e^{+}e^{-}$ pairs from the decay of vector mesons will provide the information of the partial restoration of the chiral symmetry in a normal nuclear density. To resolve a pulse pile-up and achieve good discrimination of $e^{+}$ and $e^{-}$ from the background of a reaction rate of an order of 10 MHz, the data acquisition (DAQ) system uses waveform sampling chips of APV25 and DRS4. The trigger rate and data rate are expected to be 1 kHz and 120–330 MiB/s, respectively. The DAQ system for readout of APV25 and DRS4 were developed, where events were synchronized by common trigger and tag data. The first commissioning in beam, called Run-0a, was performed in June 2020 with about 1/4 of the designed setup. The DAQ worked with a trigger rate of 300 Hz in the Run-0a and the main bottleneck was a large data size of APV25. Further optimization of the DAQ system will improve the performance.

Partially hydrolyzed guar gum (PHGG), a water-soluble dietary fiber produced by the controlled partial enzymatic hydrolysis of guar gum beans, has various physiological roles. PHGG is expected to influence the immune function and prevent infections. The objective of this study was to examine the effect of continuous ingestion of PHGG for 12 weeks on the development of cold-like symptoms.A placebo-controlled, double blind, randomized, parallel-group comparative study was conducted. 96 healthy Japanese adults received 5.2 g PHGG or placebo daily for 12 weeks. Cold-like symptoms were assessed based on patient diary, and the levels of short-chain fatty acids (SCFAs) in stool and blood immune markers at baseline and at weeks 6 and 12.The cumulative number of "no symptoms" days for all symptoms was significantly larger in the PHGG than in the placebo group. The result of the analysis by severity of cold-like symptoms also showed significant differences, with the PHGG group having a lower severity of cold-like symptoms. Propionic acid at weeks 6 and 12 and n-butyric acid and total SCFAs at week 12 were significantly higher in the PHGG than in the placebo group. The Interferon-γ level was significantly lower at week 6 in the PHGG than in the placebo group.PHGG intake may affect immune function and suppress cold-like symptoms through the production of SCFAs in healthy adults.

The widely used Streptococcus pyogenes Cas9 (SpCas9) nuclease derives its DNA targeting specificity from protein-DNA contacts with protospacer adjacent motif (PAM) sequences, in addition to base-pairing interactions between its guide RNA and target DNA. Previous reports have established that the PAM specificity of SpCas9 can be altered via positive selection procedures for directed evolution or other protein engineering strategies. Here we exploit in vivo directed evolution systems that incorporate simultaneous positive and negative selection to evolve SpCas9 variants with commensurate or improved activity on NAG PAMs relative to wild type and reduced activity on NGG PAMs, particularly YGG PAMs. We also show that the PAM preferences of available evolutionary intermediates effectively determine whether similar counterselection PAMs elicit different selection stringencies, and demonstrate that negative selection can be specifically increased in a yeast selection system through the fusion of compensatory zinc fingers to SpCas9., The PAM specificity of SpCas9 can be altered with positive selection during directed evolution. Here the authors use simultaneous positive and negative selection to improve activity on NAG PAMs while reducing activity on NGG PAMs.

A powerful approach to understand protein structure and evolution is to perform computer simulations that mimic aspects of evolution. In particular, structure-based computational protein design (CPD) can address the inverse folding problem, exploring a large space of amino acid sequences and selecting ones predicted to adopt a given fold. Previously, CPD has been used to entirely redesign several proteins: all or most of the protein sequence was allowed to mutate freely; among sampled sequences, those with low computed folding energy were selected, and a few percent of them did indeed adopt the correct fold. Those studies used an energy function that was partly or largely knowledge-based, with several empirical terms. Here, we show that a PDZ domain can be entirely redesigned using a "physics-based" energy function that combines standard molecular mechanics and a recent, continuum electrostatic solvent model. Many thousands of sequences were generated by Monte Carlo simulation. Among the lowest-energy sequences, three were chosen for experimental testing. All three could be overexpressed and had native-like circular dichroism and 1D NMR spectra. Two exhibited an upshift of their thermal denaturation curves when a peptide ligand was present, indicating they were able to bind and were most likely correctly folded. Evidently, the physical principles that govern molecular mechanics and continuum electrostatics are sufficient to perform whole-protein redesign. This is encouraging, since these methods provide physical insights, can be systematically improved, and are transferable to other biopolymers and ligands of medical or technological interest.

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.

Contains fulltext : 249977.pdf (Publisher’s version ) (Closed access) BACKGROUND: It is important to evaluate whether a new treatment for heart failure with reduced ejection fraction (HFrEF) provides additive benefit to background foundational treatments. As such, we aimed to evaluate the efficacy and safety of empagliflozin in patients with HFrEF in addition to baseline treatment with specific doses and combinations of disease-modifying therapies. METHODS: We performed a post-hoc analysis of the EMPEROR-Reduced randomised, double-blind, parallel-group trial, which took place in 520 centres (hospitals and medical clinics) in 20 countries in Asia, Australia, Europe, North America, and South America. Patients with New York Heart Association (NYHA) classification II-IV with an ejection fraction of 40% or less were randomly assigned (1:1) to receive the addition of either oral empagliflozin 10 mg per day or placebo to background therapy. The primary composite outcome was cardiovascular death and heart failure hospitalisation; the secondary outcome was total heart failure hospital admissions. An extended composite outcome consisted of inpatient and outpatient HFrEF events was also evaluated. Outcomes were analysed according to background use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs) or angiotensin receptor neprilysin inhibitors (ARNIs), as well as β blockers and mineralocorticoid receptor antagonists (MRAs) at less than 50% or 50% or more of target doses and in various combinations. This study is registered with ClinicalTrials.gov, NCT03057977. FINDINGS: In this post-hoc analysis of 3730 patients (mean age 66·8 years [SD 11·0], 893 [23·9%] women; 1863 [49·9%] in the empagliflozin group, 1867 [50·1%] in the placebo group) assessed between March 6, 2017, and May 28, 2020, empagliflozin reduced the risk of the primary outcome (361 in 1863 participants in the empagliflozin group and 462 of 1867 in the placebo group; HR 0·75 [95% CI 0·65-0·86]) regardless of background therapy or its target doses for ACE inhibitors or ARBs at doses of less than 50% of the target dose (HR 0·85 [0·69-1·06]) and for doses of 50% or more of the target dose (HR 0·67 [0·52-0·88]; p(interaction)=0·18). A similar result was seen for β blockers at doses of less than 50% of the target dose (HR 0·66 [0·54-0·80]) and for doses of 50% or more of the target dose (HR 0·81 [0·66-1·00]; p(interaction)=0·15). Empagliflozin also reduced the risk of the primary outcome irrespective of background use of triple therapy with an ACE inhibitor, ARB, or ARNI plus β blocker plus MRA (given combination HR 0·73 [0·61-0·88]; not given combination HR 0·76 [0·62-0·94]; p(interaction)=0·77). Similar patterns of benefit were observed for the secondary and extended composite outcomes. Empagliflozin was well tolerated and rates of hypotension, symptomatic hypotension, and hyperkalaemia were similar across all subgroups. INTERPRETATION: Empagliflozin reduced serious heart failure outcomes across doses and combinations of disease-modifying therapies for HFrEF. Clinically, these data suggest that empagliflozin might be considered as a foundational therapy in patients with HFrEF regardless of their existing background therapy. FUNDING: Boehringer Ingelheim and Eli Lilly and Company.

The differential cross sections of the Σ^{-}p→Λn reaction were measured accurately for the Σ^{-} momentum (p_{Σ}) ranging from 470 to 650 MeV/c at the J-PARC Hadron Experimental Facility. Precise angular information about the Σ^{-}p→Λn reaction was obtained for the first time by detecting approximately 100 reaction events at each angular step of Δcosθ=0.1. The obtained differential cross sections show a slightly forward-peaking structure in the measured momentum regions. The cross sections integrated for -0.7≤cosθ≤1.0 were obtained as 22.5±0.68 [statistical error(stat.)] ±0.65 [systematic error(syst.)] mb and 15.8±0.83(stat)±0.52(syst) mb for 470p_{Σ}(MeV/c)550 and 550p_{Σ}(MeV/c)650, respectively. These results show a drastic improvement compared with past measurements of the hyperon-proton scattering experiments. They will play essential roles in updating the theoretical models of the baryon-baryon interactions.

A scaling technique has been developed in order to predict the voltage holding capability of the world-largest electrostatic accelerator for fusion application having a long gap vacuum insulation around 1 m with large surface area of more than 6 m2. One of critical issues for design of such large-size accelerator is the development of the prediction model based on the experimental results. For this purpose, the 1/5 scale mockup has been developed, which is composed of the 5-stage accelerator with the high voltage bushing in the vacuum vessel. Direct comparison of the sustainable voltages in the 1/5 scale and full-scale high voltage busing only shows that a voltage scaling in 1/5 scale size is 55%. It was found that the voltage scaling is consistent with the prediction based on the empirical scaling according to the surface area and gap length. As a result, the voltage holding capability of the 1/5 scale mockup is 400 kV in the experiment, which indicates an estimation of 720 kV in full-scale with a real configuration. This is the first experiment-based prediction of the voltage holding capability for the largest accelerator for ITER. The improvement of the voltage holding capability has been already planned by using multi-layer electrostatic shields. In such experiment, the developed scaling technique is useful to predict the voltage holding capability for large vacuum components which can not be easily tested.

Made available in DSpace on 2020-12-10T19:38:19Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-11-01. Added 1 bitstream(s) on 2021-07-15T15:06:42Z : No. of bitstreams: 1 S1415-43662019001100860.pdf: 1244406 bytes, checksum: ff2df3422ac2dd05508131205619a4fd (MD5) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) The objective of this study was to evaluate the rooting and growth of sweet potato seedlings in trays in response to substrate supplementation with calcium (Ca) and phosphorus (P). Two greenhouse experiments were conducted in a randomized block design with a split plot scheme and eight repetitions. In the Ca experiment, the plots were the doses of 0, 100 and 200 mg kg(-1) of Ca, and in the P experiment, by the doses of 0, 150 and 300 mg kg(-1) of P. In both experiments, the subplots corresponded to the sampling time of seedlings (15, 30, 45, 60 and 75 days after planting). The Ca present in the substrate was sufficient to promote the proper rooting and growth of sweet potato seedlings in the trays. The Ca supply in excess (200 mg kg(-1)) adversely affected the growth of seedlings that remained in the tray for more than 60 days. Although the seedlings supplied with P showed higher root growth rate after 45 days, the initial P available in the substrate was sufficient to promote the adequate growth of the seedlings in the trays until 60 days. Univ Estadual Paulista, Fac Ciencias Agron, Botucatu, SP, Brazil Univ Estadual Paulista, Ctr Raizes & Amidos Trop, Botucatu, SP, Brazil Inst Fed Educ Ciencia & Tecnol Acre, Cruzeiro Do Sul, AC, Brazil Univ Estadual Paulista, Fac Ciencias Agron, Botucatu, SP, Brazil Univ Estadual Paulista, Ctr Raizes & Amidos Trop, Botucatu, SP, Brazil FAPESP: 2014/25122-4 CNPq: 301827/2017-6

The water supply must be safe and sustainable. This requires a regulatory compliance, selection of an optimal water treatment process, timely response to water quality incidents as well as maintaining internal skills and knowledge among utility personnel to keep appropriate operational standards in the long run. Water supply services in Japan face various challenges, including a shrinking revenue base due to a declining population as well as a mass retirement of the baby-boomer generation. The Japan Water Research Center conducted questionnaire surveys and based on our findings developed the ‘knowledge transfer support system for water treatment technology’ for utilities to maintain internal skills and knowledge in the face of shrinking labour forces in the water sector. The system consists of three components: the database on water treatment technology, learning program on water treatment technology, and the assessment tool for knowledge transfer on water treatment technology.

An experiment to measure an invariant mass of {\phi} mesons in nuclear medium is planned as the J-PARC E16 experiment. A trigger merging module (TRG-MRG) has been developed to detect leading-edges from 256 channels of discriminator-output signals and transmit those serialized hit data to trigger decision module with four optical links. The result of the test shows enough performance of the TRG-MRG as 1 ns TDC and data multiplexer with four 6.25 Gbps transceivers., Comment: 6 pages, 17 figures, conference record for the 21st IEEE Real Time Conference

In an emulsion-counter hybrid experiment performed at J-PARC, a Ξ^{-} absorption event was observed which decayed into twin single-Λ hypernuclei. Kinematic calculations enabled a unique identification of the reaction process as Ξ^{-}+^{14}N→_{Λ}^{10}Be+_{Λ}^{5}He. For the binding energy of the Ξ^{-} hyperon in the Ξ^{-}-^{14}N system a value of 1.27±0.21 MeV was deduced. The energy level of Ξ^{-} is likely a nuclear 1p state which indicates a weak ΞN-ΛΛ coupling.

Background Blood pressure (BP) variability has reportedly been a risk factor for various clinical events. To clarify the influence of BP visit‐to‐visit variability on adverse events in patients with nonvalvular atrial fibrillation, a post hoc analysis of the J‐RHYTHM Registry was performed. Methods and Results Of 7406 outpatients with nonvalvular atrial fibrillation from 158 institutions, 7226 (age, 69.7±9.9 years; men, 70.7%), in whom BP was measured 4 times or more (14.6±5.0 times) during the 2‐year follow‐up period or until occurrence of an event, constituted the study group. SD and coefficient of variation of BP values were calculated as BP variability. Thromboembolism, major hemorrhage, and all‐cause death occurred in 110 (1.5%), 121 (1.7%), and 168 (2.3%) patients, respectively. When patients were divided into quartiles of systolic BP‐SD (P =0.015 for thromboembolism; HR, 2.60, 95% CI, 1.36–4.97, P =0.004 for major hemorrhage; and HR, 1.85, 95% CI, 1.11–3.07, P =0.018 for all‐cause death) after adjusting for components of the CHA 2 DS 2 ‐VASc score, warfarin and antiplatelet use, atrial fibrillation type, BP measurement times, and others. These findings were consistent when BP‐coefficient of variation was used instead of BP‐SD. Conclusions Systolic BP visit‐to‐visit variability was significantly associated with all adverse events in patients with nonvalvular atrial fibrillation. Further studies are needed to clarify the causality between BP variability and adverse outcomes in patients with nonvalvular atrial fibrillation. Registration URL: https://www.umin.ac.jp/ctr/ ; Unique Identifier: UMIN000001569.

It is a widely recognized phenomenon that, in negative ion sources for NBI, the magnetic fields in the source cause an asymmetry of the current density at the meniscus, which affects the beam optics. In order to achieve a more realistic estimation of the negative ion beam optics, the ion current density profile at the beamlet meniscus is sometimes assumed to be non-symmetric with respect to the beamlet axis. The new hypothesis tested in this paper is an empirical law obtained by recent investigations on a similar Kamaboko ion source, which relates this asymmetry to the magnetic field strength at the meniscus and to the power injected in the ion source. For the first time this hypothesis is used to directly and correctly predict the value of the beamlet deflection. The MeV ion source Test Facility (MTF) is a high voltage negative ion beam accelerator dedicated to fusion experiments in QST, Naka, Ibaraki, Japan. MTF can be operated as a three- or five-stage multi-aperture accelerator with a configuration and beam energy comparable to the future ITER NBI. In 2019, experiments were conducted on MTF aiming at accelerating a H- beam with high energy and good optics for a long duration of the beam (around 100 s). These experiments allowed to measure the beamlet divergence and deflection as well as the heat loads due to particle impinging on the accelerator grids, over a wide range of operating parameters. The predictions of several beam simulation codes (Opera, COMSOL, SLACCAD, EAMCC3D) have been compared to the experimental measurements, which allows to obtain a good agreement in terms of beam optics and a fair agreement in terms of heat loads.

A novel Eclair-shaped filter magnetic field with no primary electron leakage has been proposed to reduce the co-extracted electrons and improve the spatial uniformity of negative ion production. A primary electron analysis was conducted to clarify its spatial distribution and the issue of current magnetic field configuration because the experimental data imply that the negative ion population is low on the edge segments due to the many primary electrons around there. A simulation study revealed that the low capability of electron confinement at the KAMABOKO source’s edge region due to the localized magnetically weak points induces the primary electron leakage, which causes high co-extracted electron current and negative ion non-uniformity. Calculation results showed a new design index that contributes to the complete suppression of primary electron leakage to the extraction region with a permanent magnet connection angle of 108 degrees or more. The Eclair-shaped ion source has been designed based upon the obtained index about the connection angle to realize the ideal magnetic configuration without primary electron leakage to the extraction region.

Summary Distributed acoustic sensing (DAS) is an effective method for hydraulic fracture monitoring because it has the potential to constrain fracture propagation direction and time, and monitor pressure-change effects such as stress shadowing. We have applied data processing techniques to passive DAS data recorded during a hydraulic fracturing operation in order to observe strain rate and strain response related to fracture hits along the fiber optic cable. The fracture hit position and time was estimated from the low-frequency DAS (LF-DAS) results, and in some case, fracture connection could be estimated. By integrating DAS results with distributed temperature sensing (DTS) data, we could detect temperature changes related to the compression response near the estimated fracture hit position. Furthermore, we identified opportunities to tightly constrain the timing of the fracture hit by using high-frequency DAS (HF-DAS) data. These results could be integrated with geomechanical modelling to gain further insight into the fracturing process.

Summary Application of FWI to time-lapse borehole seismic data has the potential to be a powerful solution for the successful CO2-EOR reservoir monitoring. A previous study applied acoustic FWI to the field data of time-lapse walkaway VSP acquired in Abu Dhabi. Their FWI study obtained an accurate velocity model of the baseline data with quite high resolution. In this paper, we reviewed the time-lapse FWI results for the field data. After that, we investigated an appropriate acquisition geometry and feasible timing of monitoring surveys through time-lapse velocity model building assuming CO2-EOR and a synthetic FWI study. As a result of the time-lapse FWI for the field data, 4D signals were not captured, even with the high repeatability between the baseline and monitoring data, due to the quite small amount of fluid volume injected between the surveys. As for the synthetic FWI study, we confirmed that extending receivers upward contributed to the extension of imaging area outward. On the other hand, from the monitoring perspective, deploying the receivers both above and below the target reservoir was recommended. Without the receivers below the reservoir, we found that target-oriented time-lapse FWI was effective.

A beam optics study using the ITER-relevant high intense negative ion beams, such as 1 MeV, 200 A/m2, has been performed experimentally and analytically using a multi-aperture and five-stage accelerator. Initially, multi-beamlets generated from this accelerator were deflected in various directions due to the magnetic field and space charge repulsion between beams and showed various divergences. These had limited the pulse length and the beam energy. Compensation methods of the beamlet deflections have worked effectively and contributed to achieving the ITER requirement, the divergence angle of

Beam optics of the ITER prototype accelerator with 88 mm acceleration gap length has been examined through H- beam acceleration tests at the ITER target beam perveance. The beam optics has been examined for beam energies up to 790 keV under the ITER target perveance. The total grid heat load was successfully reduced to 10 %, which was lower than the allowable value of 15 %. The beam emittance of the ITER perveance has been measured for the first time by using newly developed emittance measurement system consisting of carbon-fiber-composite (CFC) plate with pin-holes. The emittance of 790 keV H- beam shows the divergence angle of the beam core is satisfied with the ITER requirement of

A protection system of ion source components from local abnormal discharge has been developed with ITER-class filament-driven negative ion source for high power and stable long-term operation. Protection from unpredictable discharge is a common issue for filament and RF-driven ion sources. To understand how fast should be cut off the discharge, threshold energy not to cause critical damage on the filament was investigated. The experimental exploration concluded that the energy less than 1.87 J or fast cut-off faster than 343 μs is the threshold for the robust protection of the filaments. A developed system successfully detected and cut off the discharge at 100 μs under noisy environments with the high current power supply. Moreover, the detection system is remotely adjustable. Such versatile protection system can contribute to any abnormal discharges in high current system including various ion sources, gyrotron, and high voltage components.

As a challenge to measure the extraction surface of the negative ion beam, a laser Thomson scattering system with high spatial resolution was applied to a weakly ionized plasma in a negative ion source for the first time. The first target was to measure electron density around extraction region because shape of the extraction surface can be estimated by electron spatial profile. However, stray light by injected laser, filament and plasma was too intense compared to signal from the low density region. To solve this, a triple grating spectroscopy and a multilayer black screen were introduced, and the laser spot size was minimized to reduce slit sizes of the spectroscopy. As a result, electron density was successfully measured accurately in low density region. From an error estimation, measurement of electron density 3 × 1016 m-3 with spatial resolution of 0.5 mm at extraction region can be realized with accumulation of signals from multiple laser shots. This system can contribute to the understanding of the mechanism of formation of the extraction surface, which is a long-term issue in the negative ion source.

Reverse calculation of negative ion trajectory based on the measured beam emittance has been performed for the first time in multi-stage accelerator in order to reconstruct negative ion profile near meniscus, which has been a long-term issue for negative ion sources. According to reverse calculation, negative ions are mainly extracted from the periphery of extraction area, and the particles extracted from the aperture edge is lost on acceleration grids. By taking into account the lost component with reconstructed negative ion profile, the negative ion trajectory became consistent with observed beam traces on the acceleration grids. This result can be applied directly to the design of ITER accelerator as well as the other Cs-seeded negative ion sources.

In an emulsion-counter hybrid experiment performed at J-PARC, a Ξ^{-} absorption event was observed which decayed into twin single-Λ hypernuclei. Kinematic calculations enabled a unique identification of the reaction process as Ξ^{-}+^{14}N→_{Λ}^{10}Be+_{Λ}^{5}He. For the binding energy of the Ξ^{-} hyperon in the Ξ^{-}-^{14}N system a value of 1.27±0.21 MeV was deduced. The energy level of Ξ^{-} is likely a nuclear 1p state which indicates a weak ΞN-ΛΛ coupling.

16th World Congress on Public Health 2020；2020.10.12-16；Web（Rome）

International audience; In multi-beamlet negative ion accelerators for neutral beam injectors, the transverse magnetic field necessary for suppressing the co-extracted electrons induces a deflection of the negative ion beamlets that must be corrected. For the design, particle-tracing simulation codes are used to compute ion trajectories and optical properties of the beamlets in the acceleration stage. In these codes, uniform boundary conditions are normally assumed for the ion current density distribution at the surface (called meniscus), where negative ions are extracted from the plasma and form beamlets, which are accelerated across the apertures of the accelerator grids. Recently, experimental campaigns dedicated to the accurate measurement of the beamlet deflection in the acceleration phase revealed higher deflection than foreseen by simulations. In this work, we demonstrate that an agreement with the experimental data can be obtained by incorporating in the numerical simulations a non-radially symmetric distribution of the ion current density extracted across the meniscus surface. In the first part, the asymmetry of the ion current density at the meniscus is studied in an empirical way, by analysing and fitting the experimental results obtained with different operating parameters. In the second part, we show that the ion current asymmetry estimated by this procedure is well consistent with the flow pattern of H − ions calculated in the meniscus zone using a detailed particle in cell (PIC) model of the ion source in the presence of transverse magnetic field.

A new hyperon-proton scattering experiment, dubbed J-PARC E40, was performed to measure differential cross sections of the Σ+p, Σ−p elastic scatterings and the Σ−p → Λn scattering by identifying a lot of Σ particles in the momentum ranging from 0.4 to 0.8 GeV/c produced by the π±p → K+Σ± reactions. We successfully measured the differential cross sections of these three channels with a drastically improved accuracy with a fine angular step. These new data will become important experimental constraints to improve the theories of the two-body baryon-baryon interactions. Following this success, we proposed a new experiment to measure the differential cross sections and spin observables by using a highly polarized Λ beam for providing quantitative information on the ΛN interaction. The results of three Σp channels and future prospects of the Λp scattering experiment are described.

In the negative-ion-based neutral beam injector (N-NBI) of JT-60SA, a hydrogen negative ion beam with energy of 500 keV and a current density of 154 A m−2 for 118 s has been successfully demonstrated. This achievement exceeds the requirements (500 keV, 130 A m−2, 100 s) for the first time. To maintain stable negative ion production for a long pulse, the optimal temperatures of the chamber wall and plasma grid were analytically examined and were experimentally demonstrated. It was confirmed that the temperature during the beam pulse should be 200 °C for the plasma grid. Damage to the filament cathode due to an abnormal discharge, so-called arcing, has been mitigated by developing a fast cut-off system of the arc current for around 100 μs after the arcing. To maintain sufficient voltage holding capability and to reduce the grid heat load due to the beam in the accelerator, techniques developed for the beam acceleration have been applied to this test. As a result of the integration of these techniques, a stable beam over 100 s has been demonstrated successfully. This is the first achievement over a 100 s stable beam with intensity of >75 MW m−2, which is the required practical level in the N-NBI. These results contribute to the coming NBI system for ITER and DEMO.

The triple alpha reaction is one of the most important reactions in the nuclear astrophysics. However, its reaction rate in high temperature environments at T 9 > 2 was still uncertain. One of the major origins of the uncertainty was that the radiative-decay probability of the 3 1 − state in 12C was unknown. In the present work, we have determined the radiative-decay probability of the 3 1 − state to be 1.3 − 1.1 + 1.2 × 10 − 6 by measuring the 1H(12C,12Cp) reaction for the first time, and derived the triple alpha reaction rate in high temperature environments from the measured radiative-decay probability. The present result suggests that the 3 1 − state noticeably enhances the triple alpha reaction rate although the contribution from the 3 1 − state had been assumed to be small.

An experiment at J-PARC, E16 experiment, which aims to measure the spectral modification of vector meson in nuclear matter is planned. The experiment will measure light vector mesons (ρ/ω/ϕ mesons) generated in nuclear target through the 30 GeV p+A reactions. The mass spectra can be reconstructed with e^+e^− pairs originating from their decays. The spectral modification in finite baryon density is studied systematically. The detail of the experimental plan and expected results are presented with a particular focus on first physics run.

Background Presence of intimate family is considered as one of the related factors of health behaviors. The study aim was to clarify the relationship between the presence of significant others and having a colorectal cancer screening. Methods This study used data of baseline survey of intervention study regarding breast cancer screening at worksites. A total of 6827 workers, aged 40 and over of the retail company, were required to fill out a self-administrated questionnaire related to cancer screening. the intimate family was defined as a person’s spouse or partner and children. Logistic regression analyses were performed to estimate odds ratios [ORs] and 95% confidence intervals [CIs] of undergoing an annual screening for colorectal cancer by the presence of spouse or partner adjusting for age. The same analysis was performed regarding the presence of children. Results Response rates were 70% in men and 71% in women. After excluding participants with a past history of cancer and lack of information about colorectal cancer screening or the presence of significant others, 4203 remained for the analyses. A total of 1777 participants reported that they had undergone screening for colorectal cancer within a year (42% in men and 42% in women). Screening rates of participants with/without a spouse were 45% and 30% in men, 44% and 38% in women. Screening rates of participants with/without children were 45% and 33% in men, 43% and 38% in women. ORs of undergoing annual colorectal cancer screening by the presence of spouse were 1.8 (1.3-2.5) in men and 1.3 (1.1-1.5) in women. ORs by the presence of children were 1.6 (1.2-2.1) in men and 1.1 (0.9-1.3) in women. Conclusions This study indicated that health behavior in cancer screening could be affected by having a spouse in both men and women. The presence of children positively related in men. Male workers with children might be under some pressure to keep their health, from a sense of responsibility of main income earner. Key messages Health behavior in cancer screening could be affected by having a spouse. Health behavior in cancer screening could be affected by having a child only in men.

Background Vascular response after drug-eluting stent (DES) implantation depends not only on stent design but also on vulnerability of target coronary lesions. In this study, non-obstructive coronary angioscopy (CAS) revealed vascular response after two types of biodegradable polymer (BP) DES implantation into patients with acute coronary syndrome (ACS) or stable angina pectoris (SAP). Methods Eighteen Nobori BP biolimus-eluting stents (BP-BES) were successfully implanted into 15 patients (9 ACS and 9 SAP lesions). Twenty-three Ultimaster BP sirolimus-eluting stents (BP-SES) were implanted into 16 patients (6 ACS and 17 SAP lesions). At one year after stenting, CAS semi-quantified degree of neointimal stent coverage (NSC) into 4 grades (0, no coverage; 1, thin coverage; 2, thick coverage; 3, embedded in thick neointima and invisible). When NSC through a stent was composed of plural grades, CAS determined dominant, maximum and minimum NSC grades. Heterogeneity index was defined as subtraction of minimum from maximum grade. CAS also semi-quantified degree of yellow plaques (YP) into 3 grades (0, light; 1, dense; 2, glittering yellow). CAS detected presence of in-stent mural thrombi (ISMT). Results At one year after BP-BES implantation: 1) There was no significant difference with regards to dominant NSC between ACS and SAP lesions (1.00±0.50 vs. 0.89±0.60); 2) Heterogeneity index was greater in ACS than in SAP (1.22±0.44 vs. 0.67±0.50, P=0.02); 3) YP grade was greater in ACS than in SAP (1.89±0.33 vs. 1.00±1.00, P=0.02); and 4) We found one ISMT in ACS lesions and two ISMT in SAP lesions. At one year after BP-SES implantation: 1) There was neither significant difference between ACS and SAP lesions with regards to dominant NSC (1.67±1.21 vs. 1.53±1.01), with regards to heterogeneity index (0.50±0.55 vs. 0.35±0.49), nor with regards to YP grade (1.33±1.51 vs. 0.88±0.99); and 2) We found ISMT neither in ACS nor in SAP lesions. Conclusions For BP-SES implantation, vascular response at ACS lesions was similar to SAP lesions. Even one year after BP-BES implantation, however, plaque vulnerability appeared to remain in ACS lesions.