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Showing papers by "Tohoku University published in 2019"


Journal ArticleDOI
Kazunori Akiyama, Antxon Alberdi1, Walter Alef2, Keiichi Asada3  +403 moreInstitutions (82)
TL;DR: In this article, the Event Horizon Telescope was used to reconstruct event-horizon-scale images of the supermassive black hole candidate in the center of the giant elliptical galaxy M87.
Abstract: When surrounded by a transparent emission region, black holes are expected to reveal a dark shadow caused by gravitational light bending and photon capture at the event horizon. To image and study this phenomenon, we have assembled the Event Horizon Telescope, a global very long baseline interferometry array observing at a wavelength of 1.3 mm. This allows us to reconstruct event-horizon-scale images of the supermassive black hole candidate in the center of the giant elliptical galaxy M87. We have resolved the central compact radio source as an asymmetric bright emission ring with a diameter of 42 +/- 3 mu as, which is circular and encompasses a central depression in brightness with a flux ratio greater than or similar to 10: 1. The emission ring is recovered using different calibration and imaging schemes, with its diameter and width remaining stable over four different observations carried out in different days. Overall, the observed image is consistent with expectations for the shadow of a Kerr black hole as predicted by general relativity. The asymmetry in brightness in the ring can be explained in terms of relativistic beaming of the emission from a plasma rotating close to the speed of light around a black hole. We compare our images to an extensive library of ray-traced general-relativistic magnetohydrodynamic simulations of black holes and derive a central mass of M = (6.5 +/- 0.7) x 10(9) M-circle dot. Our radio-wave observations thus provide powerful evidence for the presence of supermassive black holes in centers of galaxies and as the central engines of active galactic nuclei. They also present a new tool to explore gravity in its most extreme limit and on a mass scale that was so far not accessible.

2,589 citations


Journal ArticleDOI
Peter A. R. Ade1, James E. Aguirre2, Z. Ahmed3, Simone Aiola4  +276 moreInstitutions (53)
TL;DR: The Simons Observatory (SO) is a new cosmic microwave background experiment being built on Cerro Toco in Chile, due to begin observations in the early 2020s as mentioned in this paper.
Abstract: The Simons Observatory (SO) is a new cosmic microwave background experiment being built on Cerro Toco in Chile, due to begin observations in the early 2020s. We describe the scientific goals of the experiment, motivate the design, and forecast its performance. SO will measure the temperature and polarization anisotropy of the cosmic microwave background in six frequency bands centered at: 27, 39, 93, 145, 225 and 280 GHz. The initial configuration of SO will have three small-aperture 0.5-m telescopes and one large-aperture 6-m telescope, with a total of 60,000 cryogenic bolometers. Our key science goals are to characterize the primordial perturbations, measure the number of relativistic species and the mass of neutrinos, test for deviations from a cosmological constant, improve our understanding of galaxy evolution, and constrain the duration of reionization. The small aperture telescopes will target the largest angular scales observable from Chile, mapping ≈ 10% of the sky to a white noise level of 2 μK-arcmin in combined 93 and 145 GHz bands, to measure the primordial tensor-to-scalar ratio, r, at a target level of σ(r)=0.003. The large aperture telescope will map ≈ 40% of the sky at arcminute angular resolution to an expected white noise level of 6 μK-arcmin in combined 93 and 145 GHz bands, overlapping with the majority of the Large Synoptic Survey Telescope sky region and partially with the Dark Energy Spectroscopic Instrument. With up to an order of magnitude lower polarization noise than maps from the Planck satellite, the high-resolution sky maps will constrain cosmological parameters derived from the damping tail, gravitational lensing of the microwave background, the primordial bispectrum, and the thermal and kinematic Sunyaev-Zel'dovich effects, and will aid in delensing the large-angle polarization signal to measure the tensor-to-scalar ratio. The survey will also provide a legacy catalog of 16,000 galaxy clusters and more than 20,000 extragalactic sources.

1,027 citations


Journal ArticleDOI
Kazunori Akiyama, Antxon Alberdi1, Walter Alef2, Keiichi Asada3  +251 moreInstitutions (56)
TL;DR: In this article, the authors present measurements of the properties of the central radio source in M87 using Event Horizon Telescope data obtained during the 2017 campaign, and find that >50% of the total flux at arcsecond scales comes from near the horizon and that the emission is dramatically suppressed interior to this region by a factor >10, providing direct evidence of the predicted shadow of a black hole.
Abstract: We present measurements of the properties of the central radio source in M87 using Event Horizon Telescope data obtained during the 2017 campaign. We develop and fit geometric crescent models (asymmetric rings with interior brightness depressions) using two independent sampling algorithms that consider distinct representations of the visibility data. We show that the crescent family of models is statistically preferred over other comparably complex geometric models that we explore. We calibrate the geometric model parameters using general relativistic magnetohydrodynamic (GRMHD) models of the emission region and estimate physical properties of the source. We further fit images generated from GRMHD models directly to the data. We compare the derived emission region and black hole parameters from these analyses with those recovered from reconstructed images. There is a remarkable consistency among all methods and data sets. We find that >50% of the total flux at arcsecond scales comes from near the horizon, and that the emission is dramatically suppressed interior to this region by a factor >10, providing direct evidence of the predicted shadow of a black hole. Across all methods, we measure a crescent diameter of 42 ± 3 μas and constrain its fractional width to be <0.5. Associating the crescent feature with the emission surrounding the black hole shadow, we infer an angular gravitational radius of GM/Dc2 = 3.8 ± 0.4 μas. Folding in a distance measurement of ${16.8}_{-0.7}^{+0.8}\,\mathrm{Mpc}$ gives a black hole mass of $M=6.5\pm 0.2{| }_{\mathrm{stat}}\pm 0.7{| }_{\mathrm{sys}}\times {10}^{9}\hspace{2pt}{M}_{\odot }$. This measurement from lensed emission near the event horizon is consistent with the presence of a central Kerr black hole, as predicted by the general theory of relativity.

1,024 citations


Journal ArticleDOI
Kazunori Akiyama, Antxon Alberdi1, Walter Alef2, Keiichi Asada3  +251 moreInstitutions (58)
TL;DR: In this article, the first Event Horizon Telescope (EHT) images of M87 were presented, using observations from April 2017 at 1.3 mm wavelength, showing a prominent ring with a diameter of ~40 μas, consistent with the size and shape of the lensed photon orbit encircling the "shadow" of a supermassive black hole.
Abstract: We present the first Event Horizon Telescope (EHT) images of M87, using observations from April 2017 at 1.3 mm wavelength. These images show a prominent ring with a diameter of ~40 μas, consistent with the size and shape of the lensed photon orbit encircling the "shadow" of a supermassive black hole. The ring is persistent across four observing nights and shows enhanced brightness in the south. To assess the reliability of these results, we implemented a two-stage imaging procedure. In the first stage, four teams, each blind to the others' work, produced images of M87 using both an established method (CLEAN) and a newer technique (regularized maximum likelihood). This stage allowed us to avoid shared human bias and to assess common features among independent reconstructions. In the second stage, we reconstructed synthetic data from a large survey of imaging parameters and then compared the results with the corresponding ground truth images. This stage allowed us to select parameters objectively to use when reconstructing images of M87. Across all tests in both stages, the ring diameter and asymmetry remained stable, insensitive to the choice of imaging technique. We describe the EHT imaging procedures, the primary image features in M87, and the dependence of these features on imaging assumptions.

952 citations


Journal ArticleDOI
TL;DR: The story of the life and times of Toshihiko Umemura and his family in the years leading up to and including his death.
Abstract: Satoshi Umemura ● Hisatomi Arima ● Shuji Arima ● Kei Asayama ● Yasuaki Dohi ● Yoshitaka Hirooka ● Takeshi Horio ● Satoshi Hoshide ● Shunya Ikeda ● Toshihiko Ishimitsu ● Masaaki Ito ● Sadayoshi Ito ● Yoshio Iwashima ● Hisashi Kai ● Kei Kamide ● Yoshihiko Kanno ● Naoki Kashihara ● Yuhei Kawano ● Toru Kikuchi ● Kazuo Kitamura ● Takanari Kitazono ● Katsuhiko Kohara ● Masataka Kudo ● Hiroo Kumagai ● Kiyoshi Matsumura ● Hideo Matsuura ● Katsuyuki Miura ● Masashi Mukoyama ● Satoko Nakamura ● Takayoshi Ohkubo ● Yusuke Ohya ● Takafumi Okura ● Hiromi Rakugi ● Shigeyuki Saitoh ● Hirotaka Shibata ● Tatsuo Shimosawa ● Hiromichi Suzuki ● Shori Takahashi ● Kouichi Tamura ● Hirofumi Tomiyama ● Takuya Tsuchihashi ● Shinichiro Ueda ● Yoshinari Uehara ● Hidenori Urata ● Nobuhito Hirawa

903 citations


Journal ArticleDOI
Kazunori Akiyama, Antxon Alberdi1, Walter Alef2, Keiichi Asada3  +259 moreInstitutions (62)
TL;DR: In this article, a large library of models based on general relativistic magnetohydrodynamic (GRMHD) simulations and synthetic images produced by GRS was constructed and compared with the observed visibilities.
Abstract: The Event Horizon Telescope (EHT) has mapped the central compact radio source of the elliptical galaxy M87 at 1.3 mm with unprecedented angular resolution. Here we consider the physical implications of the asymmetric ring seen in the 2017 EHT data. To this end, we construct a large library of models based on general relativistic magnetohydrodynamic (GRMHD) simulations and synthetic images produced by general relativistic ray tracing. We compare the observed visibilities with this library and confirm that the asymmetric ring is consistent with earlier predictions of strong gravitational lensing of synchrotron emission from a hot plasma orbiting near the black hole event horizon. The ring radius and ring asymmetry depend on black hole mass and spin, respectively, and both are therefore expected to be stable when observed in future EHT campaigns. Overall, the observed image is consistent with expectations for the shadow of a spinning Kerr black hole as predicted by general relativity. If the black hole spin and M87's large scale jet are aligned, then the black hole spin vector is pointed away from Earth. Models in our library of non-spinning black holes are inconsistent with the observations as they do not produce sufficiently powerful jets. At the same time, in those models that produce a sufficiently powerful jet, the latter is powered by extraction of black hole spin energy through mechanisms akin to the Blandford-Znajek process. We briefly consider alternatives to a black hole for the central compact object. Analysis of existing EHT polarization data and data taken simultaneously at other wavelengths will soon enable new tests of the GRMHD models, as will future EHT campaigns at 230 and 345 GHz.

808 citations


Journal ArticleDOI
01 Jan 2019
TL;DR: In this article, the potential use of ammonia as a carbon-free fuel is discussed, and recent advances in the development of ammonia combustion technology and its underlying chemistry are discussed. But, there are several challenges in ammonia combustion, such as low flammability, high NOx emission, and low radiation intensity.
Abstract: This paper focuses on the potential use of ammonia as a carbon-free fuel, and covers recent advances in the development of ammonia combustion technology and its underlying chemistry. Fulfilling the COP21 Paris Agreement requires the de-carbonization of energy generation, through utilization of carbon-neutral and overall carbon-free fuels produced from renewable sources. Hydrogen is one of such fuels, which is a potential energy carrier for reducing greenhouse-gas emissions. However, its shipment for long distances and storage for long times present challenges. Ammonia on the other hand, comprises 17.8% of hydrogen by mass and can be produced from renewable hydrogen and nitrogen separated from air. Furthermore, thermal properties of ammonia are similar to those of propane in terms of boiling temperature and condensation pressure, making it attractive as a hydrogen and energy carrier. Ammonia has been produced and utilized for the past 100 years as a fertilizer, chemical raw material, and refrigerant. Ammonia can be used as a fuel but there are several challenges in ammonia combustion, such as low flammability, high NOx emission, and low radiation intensity. Overcoming these challenges requires further research into ammonia flame dynamics and chemistry. This paper discusses recent successful applications of ammonia fuel, in gas turbines, co-fired with pulverize coal, and in industrial furnaces. These applications have been implemented under the Japanese ‘Cross-ministerial Strategic Innovation Promotion Program (SIP): Energy Carriers’. In addition, fundamental aspects of ammonia combustion are discussed including characteristics of laminar premixed flames, counterflow twin-flames, and turbulent premixed flames stabilized by a nozzle burner at high pressure. Furthermore, this paper discusses details of the chemistry of ammonia combustion related to NOx production, processes for reducing NOx, and validation of several ammonia oxidation kinetics models. Finally, LES results for a gas-turbine-like swirl-burner are presented, for the purpose of developing low-NOx single-fuelled ammonia gas turbine combustors.

768 citations


Journal ArticleDOI
Kazunori Akiyama, Antxon Alberdi1, Walter Alef2, Keiichi Asada3  +394 moreInstitutions (78)
TL;DR: The Event Horizon Telescope (EHT) as mentioned in this paper is a very long baseline interferometry (VLBI) array that comprises millimeter and submillimeter-wavelength telescopes separated by distances comparable to the diameter of the Earth.
Abstract: The Event Horizon Telescope (EHT) is a very long baseline interferometry (VLBI) array that comprises millimeter- and submillimeter-wavelength telescopes separated by distances comparable to the diameter of the Earth. At a nominal operating wavelength of ~1.3 mm, EHT angular resolution (λ/D) is ~25 μas, which is sufficient to resolve nearby supermassive black hole candidates on spatial and temporal scales that correspond to their event horizons. With this capability, the EHT scientific goals are to probe general relativistic effects in the strong-field regime and to study accretion and relativistic jet formation near the black hole boundary. In this Letter we describe the system design of the EHT, detail the technology and instrumentation that enable observations, and provide measures of its performance. Meeting the EHT science objectives has required several key developments that have facilitated the robust extension of the VLBI technique to EHT observing wavelengths and the production of instrumentation that can be deployed on a heterogeneous array of existing telescopes and facilities. To meet sensitivity requirements, high-bandwidth digital systems were developed that process data at rates of 64 gigabit s^(−1), exceeding those of currently operating cm-wavelength VLBI arrays by more than an order of magnitude. Associated improvements include the development of phasing systems at array facilities, new receiver installation at several sites, and the deployment of hydrogen maser frequency standards to ensure coherent data capture across the array. These efforts led to the coordination and execution of the first Global EHT observations in 2017 April, and to event-horizon-scale imaging of the supermassive black hole candidate in M87.

756 citations


Journal ArticleDOI
01 Feb 2019
TL;DR: In this article, the basic concepts of magnetic topological insulators and their experimental realization, together with the discovery and verification of their emergent properties are summarized. And the development of tailored materials through heterostructure engineering has made it possible to access the quantum anomalous Hall effect, topological magnetoelectric effect, the physics related to the chiral edge states that appear in these materials and various spintronic phenomena.
Abstract: The importance of global band topology is unequivocally recognized in condensed matter physics, and new states of matter, such as topological insulators, have been discovered. Owing to their bulk band topology, 3D topological insulators possess a massless Dirac dispersion with spin–momentum locking at the surface. Although 3D topological insulators were originally proposed in time-reversal invariant systems, the onset of a spontaneous magnetization or, equivalently, a broken time-reversal symmetry leads to the formation of an exchange gap in the Dirac band dispersion. In such magnetic topological insulators, tuning of the Fermi level in the exchange gap results in the emergence of a quantum Hall effect at zero magnetic field, that is, of a quantum anomalous Hall effect. Here, we review the basic concepts of magnetic topological insulators and their experimental realization, together with the discovery and verification of their emergent properties. In particular, we discuss how the development of tailored materials through heterostructure engineering has made it possible to access the quantum anomalous Hall effect, the topological magnetoelectric effect, the physics related to the chiral edge states that appear in these materials and various spintronic phenomena. Further theoretical and experimental research on magnetic topological insulators will provide fertile ground for the development of new concepts for next-generation electronic devices for applications such as spintronics with low energy consumption, dissipationless topological electronics and topological quantum computation. Magnetic topological insulators enable the investigation of the interplay between magnetism and topological electronic states. This Review summarizes the basic notions of magnetic topological insulators and the progress in the experimental realization of exotic topological phenomena.

701 citations


Journal ArticleDOI
Kazunori Akiyama, Antxon Alberdi1, Walter Alef2, Keiichi Asada3  +243 moreInstitutions (60)
TL;DR: In this paper, the Event Horizon Telescope (EHT) 1.3 mm radio wavelength observations of the supermassive black hole candidate at the center of the radio galaxy M87 and the quasar 3C 279, taken during the 2017 April 5-11 observing campaign are presented.
Abstract: We present the calibration and reduction of Event Horizon Telescope (EHT) 1.3 mm radio wavelength observations of the supermassive black hole candidate at the center of the radio galaxy M87 and the quasar 3C 279, taken during the 2017 April 5–11 observing campaign. These global very long baseline interferometric observations include for the first time the highly sensitive Atacama Large Millimeter/submillimeter Array (ALMA); reaching an angular resolution of 25 μas, with characteristic sensitivity limits of ~1 mJy on baselines to ALMA and ~10 mJy on other baselines. The observations present challenges for existing data processing tools, arising from the rapid atmospheric phase fluctuations, wide recording bandwidth, and highly heterogeneous array. In response, we developed three independent pipelines for phase calibration and fringe detection, each tailored to the specific needs of the EHT. The final data products include calibrated total intensity amplitude and phase information. They are validated through a series of quality assurance tests that show consistency across pipelines and set limits on baseline systematic errors of 2% in amplitude and 1° in phase. The M87 data reveal the presence of two nulls in correlated flux density at ~3.4 and ~8.3 Gλ and temporal evolution in closure quantities, indicating intrinsic variability of compact structure on a timescale of days, or several light-crossing times for a few billion solar-mass black hole. These measurements provide the first opportunity to image horizon-scale structure in M87.

625 citations


Journal ArticleDOI
TL;DR: Overall survival was significantly improved in the nivolumab group compared with the chemotherapy group, and a favourable safety profile compared with chemotherapy in previously treated advanced oesophageal squamous cell carcinoma patients.
Abstract: Summary Background Chemotherapy for patients with advanced oesophageal squamous cell carcinoma offers poor long-term survival prospects. We report the final analysis from our study of the immune checkpoint PD-1 inhibitor nivolumab versus chemotherapy in patients with previously treated advanced oesophageal squamous cell carcinoma. Methods We did a multicentre, randomised, open-label, phase 3 trial (ATTRACTION-3) at 90 hospitals and cancer centres in Denmark, Germany, Italy, Japan, South Korea, Taiwan, the UK, and the USA. We enrolled patients aged 20 years and older with unresectable advanced or recurrent oesophageal squamous cell carcinoma (regardless of PD-L1 expression), at least one measurable or non-measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, a baseline Eastern Cooperative Oncology Group performance status of 0–1, and who were refractory or intolerant to one previous fluoropyrimidine-based and platinum-based chemotherapy and had a life expectancy of at least 3 months. Patients were randomly assigned (1:1) to either nivolumab (240 mg for 30 min every 2 weeks) or investigator's choice of chemotherapy (paclitaxel 100 mg/m2 for at least 60 min once per week for 6 weeks then 1 week off; or docetaxel 75 mg/m2 for at least 60 min every 3 weeks), all given intravenously. Treatment continued until disease progression assessed by the investigator per RECIST version 1.1 or unacceptable toxicity. Randomisation was done using an interactive web response system with a block size of four and stratified according to geographical region (Japan vs rest of the world), number of organs with metastases, and PD-L1 expression. Patients and investigators were not masked to treatment allocation. The primary endpoint was overall survival, defined as the time from randomisation until death from any cause, in the intention-to-treat population that included all randomly assigned patients. Safety was assessed in all patients who received at least one dose of the assigned treatment. This trial is registered with ClinicalTrials.gov , number NCT02569242 , and follow-up for long-term outcomes is ongoing. Findings Between Jan 7, 2016, and May 25, 2017, we assigned 419 patients to treatment: 210 to nivolumab and 209 to chemotherapy. At the time of data cutoff on Nov 12, 2018, median follow-up for overall survival was 10·5 months (IQR 4·5–19·0) in the nivolumab group and 8·0 months (4·6–15·2) in the chemotherapy group. At a minimum follow-up time (ie, time from random assignment of the last patient to data cutoff) of 17·6 months, overall survival was significantly improved in the nivolumab group compared with the chemotherapy group (median 10·9 months, 95% CI 9·2–13·3 vs 8·4 months, 7·2–9·9; hazard ratio for death 0·77, 95% CI 0·62–0·96; p=0·019). 38 (18%) of 209 patients in the nivolumab group had grade 3 or 4 treatment-related adverse events compared with 131 (63%) of 208 patients in the chemotherapy group. The most frequent grade 3 or 4 treatment-related adverse events were anaemia (four [2%]) in the nivolumab group and decreased neutrophil count (59 [28%]) in the chemotherapy group. Five deaths were deemed treatment-related: two in the nivolumab group (one each of interstitial lung disease and pneumonitis) and three in the chemotherapy group (one each of pneumonia, spinal cord abscess, and interstitial lung disease). Interpretation Nivolumab was associated with a significant improvement in overall survivaland a favourable safety profile compared with chemotherapy in previously treated patients with advanced oesophageal squamous cell carcinoma, and might represent a new standard second-line treatment option for these patients. Funding ONO Pharmaceutical and Bristol-Myers Squibb.

Journal ArticleDOI
TL;DR: Patients with AQP4-IgG-positive NMOSD who received eculizumab had a significantly lower risk of relapse than those who received placebo, and there was no significant between-group difference in measures of disability progression.
Abstract: Background Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing, autoimmune, inflammatory disorder that typically affects the optic nerves and spinal cord. At least two thirds of ...

Journal ArticleDOI
TL;DR: In this paper, the abundance of primordial black holes in the Galactic halo is constrained through their microlensing of stars in M31, but only a single candidate event is found, providing stringent upper bounds on their abundance.
Abstract: Primordial black holes (PBHs) have long been suggested as a viable candidate for the elusive dark matter. The abundance of such PBHs has been constrained using a number of astrophysical observations, except for a hitherto unexplored mass window of MPBH = [10−14, 10−9] solar masses. Here we carry out a dense-cadence, 7-hour-long observation of M31 with the Subaru Hyper Suprime-Cam (HSC) to search for microlensing of stars in M31 by PBHs lying in the halo regions of the Milky Way and M31. Given our simultaneous monitoring of tens of millions of stars in M31, if such light PBHs make up a significant fraction of dark matter, we expect to find many microlensing events. However, we identify only a single candidate event, which translates into stringent upper bounds on the abundance of PBHs in the mass range MPBH ≃ [10−11, 10−6] solar masses. The abundance of primordial black holes in the Galactic halo is constrained through their microlensing of stars in M31. Despite monitoring tens of millions of stars, only a single candidate event is found, providing stringent upper bounds on their abundance.

Journal ArticleDOI
TL;DR: A phase 3 trial to validate the results of the JO25567 study and report here the results from the preplanned interim analysis of the NEJ026 trial, which established the activity and manageable toxicity of erlotinib plus bevacizumab in patients with NSCLC.
Abstract: Summary Background Resistance to first-generation or second-generation EGFR tyrosine kinase inhibitor (TKI) monotherapy develops in almost half of patients with EGFR-positive non-small-cell lung cancer (NSCLC) after 1 year of treatment. The JO25567 phase 2 trial comparing erlotinib plus bevacizumab combination therapy with erlotinib monotherapy established the activity and manageable toxicity of erlotinib plus bevacizumab in patients with NSCLC. We did a phase 3 trial to validate the results of the JO25567 study and report here the results from the preplanned interim analysis. Methods In this prespecified interim analysis of the randomised, open-label, phase 3 NEJ026 trial, we recruited patients with stage IIIB–IV disease or recurrent, cytologically or histologically confirmed non-squamous NSCLC with activating EGFR genomic aberrations from 69 centres across Japan. Eligible patients were at least 20 years old, and had an Eastern Cooperative Oncology Group performance status of 2 or lower, no previous chemotherapy for advanced disease, and one or more measurable lesions based on Response Evaluation Criteria in Solid Tumours (1.1). Patients were randomly assigned (1:1) to receive oral erlotinib 150 mg per day plus intravenous bevacizumab 15 mg/kg once every 21 days, or erlotinib 150 mg per day monotherapy. Randomisation was done by minimisation, stratified by sex, smoking status, clinical stage, and EGFR mutation subtype. The primary endpoint was progression-free survival. This study is ongoing; the data cutoff for this prespecified interim analysis was Sept 21, 2017. Efficacy was analysed in the modified intention-to-treat population, which included all randomly assigned patients who received at least one dose of treatment and had at least one response evaluation. Safety was analysed in all patients who received at least one dose of study drug. The trial is registered with the University Hospital Medical Information Network Clinical Trials Registry, number UMIN000017069. Findings Between June 3, 2015, and Aug 31, 2016, 228 patients were randomly assigned to receive erlotinib plus bevacizumab (n=114) or erlotinib alone (n=114). 112 patients in each group were evaluable for efficacy, and safety was evaluated in 112 patients in the combination therapy group and 114 in the monotherapy group. Median follow-up was 12·4 months (IQR 7·0–15·7). At the time of interim analysis, median progression-free survival for patients in the erlotinib plus bevacizumab group was 16·9 months (95% CI 14·2–21·0) compared with 13·3 months (11·1–15·3) for patients in the erlotinib group (hazard ratio 0·605, 95% CI 0·417–0·877; p=0·016). 98 (88%) of 112 patients in the erlotinib plus bevacizumab group and 53 (46%) of 114 patients in the erlotinib alone group had grade 3 or worse adverse events. The most common grade 3–4 adverse event was rash (23 [21%] of 112 patients in the erlotinib plus bevacizumab group vs 24 [21%] of 114 patients in the erlotinib alone group). Nine (8%) of 112 patients in the erlotinib plus bevacizumab group and five (4%) of 114 patients in the erlotinib alone group had serious adverse events. The most common serious adverse events were grade 4 neutropenia (two [2%] of 112 patients in the erlotinib plus bevacizumab group) and grade 4 hepatic dysfunction (one [1%] of 112 patients in the erlotinib plus bevacizumab group and one [1%] of 114 patients in the erlotinib alone group). No treatment-related deaths occurred. Interpretation The results of this interim analysis showed that bevacizumab plus erlotinib combination therapy improves progression-free survival compared with erlotinib alone in patients with EGFR-positive NSCLC. Future studies with longer follow-up, and overall survival and quality-of-life data will be required to further assess the efficacy of this combination in this setting. Funding Chugai Pharmaceutical.

Journal ArticleDOI
TL;DR: This Review discusses structure prediction methods, examining their potential for the study of different materials systems, and presents examples of computationally driven discoveries of new materials — including superhard materials, superconductors and organic materials — that will enable new technologies.
Abstract: Progress in the discovery of new materials has been accelerated by the development of reliable quantum-mechanical approaches to crystal structure prediction. The properties of a material depend very sensitively on its structure; therefore, structure prediction is the key to computational materials discovery. Structure prediction was considered to be a formidable problem, but the development of new computational tools has allowed the structures of many new and increasingly complex materials to be anticipated. These widely applicable methods, based on global optimization and relying on little or no empirical knowledge, have been used to study crystalline structures, point defects, surfaces and interfaces. In this Review, we discuss structure prediction methods, examining their potential for the study of different materials systems, and present examples of computationally driven discoveries of new materials — including superhard materials, superconductors and organic materials — that will enable new technologies. Advances in first-principle structure predictions also lead to a better understanding of physical and chemical phenomena in materials. Recent breakthroughs in crystal structure prediction have enabled the discovery of new materials and of new physical and chemical phenomena. This Review surveys structure prediction methods and presents examples of results in different classes of materials.

Journal ArticleDOI
Sei-ichiro Watanabe1, Sei-ichiro Watanabe2, Masatoshi Hirabayashi3, Naru Hirata4, Na. Hirata5, Rina Noguchi1, Yuri Shimaki1, H. Ikeda, Eri Tatsumi6, Makoto Yoshikawa7, Makoto Yoshikawa1, Shota Kikuchi1, Hikaru Yabuta8, Tomoki Nakamura9, Shogo Tachibana1, Shogo Tachibana6, Yoshiaki Ishihara1, Tomokatsu Morota2, Kohei Kitazato4, Naoya Sakatani1, Koji Matsumoto7, Koji Wada10, Hiroki Senshu10, C. Honda4, Tatsuhiro Michikami11, Hiroshi Takeuchi7, Hiroshi Takeuchi1, Toru Kouyama12, R. Honda13, Shingo Kameda14, Tetsuharu Fuse15, Hideaki Miyamoto6, Goro Komatsu10, S. Sugita6, Tatsuaki Okada6, Tatsuaki Okada1, Noriyuki Namiki7, Masahiko Arakawa5, Masateru Ishiguro16, Masanao Abe1, Masanao Abe7, Robert Gaskell17, Eric Palmer17, Olivier S. Barnouin18, Patrick Michel19, A. S. French20, Jay W. McMahon20, Daniel J. Scheeres20, Paul A. Abell, Yukio Yamamoto7, Yukio Yamamoto1, Satoshi Tanaka1, Satoshi Tanaka7, Kei Shirai1, Moe Matsuoka1, Manabu Yamada10, Y. Yokota1, Y. Yokota13, H. Suzuki21, Kosuke Yoshioka6, Yuichiro Cho6, Naoki Nishikawa5, T. Sugiyama4, Hideaki Kikuchi6, Ryodo Hemmi6, Tomohiro Yamaguchi1, Naoko Ogawa1, Go Ono, Yuya Mimasu1, Kent Yoshikawa, T. Takahashi1, Yuto Takei1, Atsushi Fujii1, Chikako Hirose, Takahiro Iwata7, Takahiro Iwata1, Masahiro Hayakawa1, Satoshi Hosoda1, Osamu Mori1, Hirotaka Sawada1, Takanobu Shimada1, Stefania Soldini1, Hajime Yano1, Hajime Yano7, Ryudo Tsukizaki1, M. Ozaki1, M. Ozaki7, Yuichi Iijima1, K. Ogawa5, Masaki Fujimoto1, T. M. Ho22, Aurelie Moussi23, Ralf Jaumann, J. P. Bibring, Christian Krause, Fuyuto Terui1, Takanao Saiki1, Satoru Nakazawa1, Yoshiyuki Tsuda7, Yoshiyuki Tsuda1 
19 Mar 2019-Science
TL;DR: The Hayabusa2 spacecraft measured the mass, size, shape, density, and spin rate of asteroid Ryugu, showing that it is a porous rubble pile, and observations of Ryugu's shape, mass, and geomorphology suggest that Ryugu was reshaped by centrifugally induced deformation during a period of rapid rotation.
Abstract: The Hayabusa2 spacecraft arrived at the near-Earth carbonaceous asteroid 162173 Ryugu in 2018. We present Hayabusa2 observations of Ryugu’s shape, mass, and geomorphology. Ryugu has an oblate “spinning top” shape, with a prominent circular equatorial ridge. Its bulk density, 1.19 ± 0.02 grams per cubic centimeter, indicates a high-porosity (>50%) interior. Large surface boulders suggest a rubble-pile structure. Surface slope analysis shows Ryugu’s shape may have been produced from having once spun at twice the current rate. Coupled with the observed global material homogeneity, this suggests that Ryugu was reshaped by centrifugally induced deformation during a period of rapid rotation. From these remote-sensing investigations, we identified a suitable sample collection site on the equatorial ridge.

Journal ArticleDOI
TL;DR: This English language document is a revised digest version of Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure (JCS 2017/JHFS 2017) reported at the Japanese Circulation Society Joint Working Groups performed in 2017.
Abstract: J-STAGE Advance Publication released online September 10, 2019 Mailing address: Scientific Committee of the Japanese Circulation Society, 18F Imperial Hotel Tower, 1-1-1 Uchisaiwai-cho, Chiyoda-ku, Tokyo 100-0011, Japan. E-mail: meeting@j-circ.or.jp This English language document is a revised digest version of Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure (JCS 2017/JHFS 2017) reported at the Japanese Circulation Society Joint Working Groups performed in 2017 (Website: http://www.j-circ.or.jp/guideline/pdf/JCS2017_tsutsui_d.pdf). Joint Working Groups: The Japanese Circulation Society; the Japanese Heart Failure Society; the Japanese Association for Thoracic Surgery; the Japanese Society of Hypertension; the Japanese Society of Echocardiography; the Japanese Society for Cardiovascular Surgery; the Japanese College of Cardiology; the Japanese Association of Cardiac Rehabilitation; the Japan Society of Ultrasonics in Medicine; the Japan Diabetes Society; the Japanese Heart Rhythm Society; “the Study Group on Idiopathic Cardiomyopathy” supported by the Health and Labor Sciences Research Grant on Intractable Diseases; and “the Study Group on the Multi-center Observational Study of Dilatedphase Hypertrophic Cardiomyopathy”, supported by the “Practical Research Project for Rare/ intractable Diseases by the Japan Agency for Medical Research and Development”. ISSN-1346-9843 All rights are reserved to the Japanese Circulation Society. For permissions, please e-mail: cj@j-circ.or.jp JCS 2017/JHFS 2017 Guideline on Diagnosis and Treatment of Acute and Chronic Heart Failure ― Digest Version ―

Journal ArticleDOI
TL;DR: In this paper, the authors review the recent advances on the understanding of structural heterogeneities in metallic supercooled liquids and the influence of the structural heterogeneity on the overall mechanical properties of the corresponding amorphous alloys.

Journal ArticleDOI
TL;DR: In this paper, a hybrid electrocatalyst comprising atomically dispersed Ni−Nx species anchored porous carbon (Ni-N-C) matrix with embedded Ni nanoparticles for hydrogen evolution reaction (HER) during alkaline water electrolysis is reported.
Abstract: Developing inexpensive and efficient electrocatalysts for hydrogen evolution reaction (HER) during alkaline water electrolysis is crucial for renewable and sustainable energy harvesting. Herein, we report a novel hybrid electrocatalyst comprising atomically dispersed Ni–Nx species anchored porous carbon (Ni–N–C) matrix with embedded Ni nanoparticles for HER. This new catalyst is synthesized via pyrolysis of hydrothermally prepared supermolecular composite of dicyandiamide and Ni ions followed by an acid etching treatment. The achieved hybrid exhibits superior catalytic performance toward HER with a small overpotential of 147 mV at 10 mA cm−2 and a low Tafel slope of 114 mV dec−1, comparable to those of state-of-the-art heteroatom-doped nanocarbon catalysts and even outperforming other reported transition-metal-based compounds in basic media. Experimental observations and theoretical calculations reveal that the presence of Ni nanoparticles can optimize surface states of Ni−Nx active centers and reduce energy barriers of dissociated water molecules, which synergistically improve OH− adsorption and promote HER kinetics. When served as electrodes for both cathode and anode, an alkaline water electrolyzer could afford a current density of 10 mA cm−2 at a low cell voltage of 1.58 V, rivalling the sufficiently high overpotentials of integrated Pt/C–Ir/C benchmark electrodes.

Journal ArticleDOI
TL;DR: In this paper, the authors report atomically dispersed nickel coordinated with nitrogen and sulfur species in porous carbon nanosheets as an electrocatalyst exhibiting excellent activity and durability for oxygen evolution reaction (OER).
Abstract: Developing low-cost electrocatalysts to replace precious Ir-based materials is key for oxygen evolution reaction (OER). Here, we report atomically dispersed nickel coordinated with nitrogen and sulfur species in porous carbon nanosheets as an electrocatalyst exhibiting excellent activity and durability for OER with a low overpotential of 1.51 V at 10 mA cm−2 and a small Tafel slope of 45 mV dec−1 in alkaline media. Such electrocatalyst represents the best among all reported transition metal- and/or heteroatom-doped carbon electrocatalysts and is even superior to benchmark Ir/C. Theoretical and experimental results demonstrate that the well-dispersed molecular S|NiNx species act as active sites for catalyzing OER. The atomic structure of S|NiNx centers in the carbon matrix is clearly disclosed by aberration-corrected scanning transmission electron microscopy and synchrotron radiation X-ray absorption spectroscopy together with computational simulations. An integrated photoanode of nanocarbon on a Fe2O3 nanosheet array enables highly active solar-driven oxygen production. Water oxidation is considered the bottleneck reaction for light-driven water splitting due to the sluggish kinetics and poor stability. Here, authors show metal- and heteroatom-doped carbons as effective catalysts for both electrochemical and photoelectrochemical water splitting.

Journal ArticleDOI
TL;DR: Wannier90 as mentioned in this paper is an open-source computer program for calculating maximally-localised Wannier functions (MLWFs) from a set of Bloch states, which is interfaced to many widely used electronic-structure codes thanks to its independence from the basis sets representing these BLoch states.
Abstract: Wannier90 is an open-source computer program for calculating maximally-localised Wannier functions (MLWFs) from a set of Bloch states. It is interfaced to many widely used electronic-structure codes thanks to its independence from the basis sets representing these Bloch states. In the past few years the development of Wannier90 has transitioned to a community-driven model; this has resulted in a number of new developments that have been recently released in Wannier90 v3.0. In this article we describe these new functionalities, that include the implementation of new features for wannierisation and disentanglement (symmetry-adapted Wannier functions, selectively-localised Wannier functions, selected columns of the density matrix) and the ability to calculate new properties (shift currents and Berry-curvature dipole, and a new interface to many-body perturbation theory); performance improvements, including parallelisation of the core code; enhancements in functionality (support for spinor-valued Wannier functions, more accurate methods to interpolate quantities in the Brillouin zone); improved usability (improved plotting routines, integration with high-throughput automation frameworks), as well as the implementation of modern software engineering practices (unit testing, continuous integration, and automatic source-code documentation). These new features, capabilities, and code development model aim to further sustain and expand the community uptake and range of applicability, that nowadays spans complex and accurate dielectric, electronic, magnetic, optical, topological and transport properties of materials.

Journal ArticleDOI
Vassilis Angelopoulos1, P. Cruce1, Alexander Drozdov1, Eric Grimes1, N. Hatzigeorgiu2, D. A. King2, Davin Larson2, James W. Lewis2, J. M. McTiernan2, D. A. Roberts3, C. L. Russell1, Tomoaki Hori4, Yoshiya Kasahara5, Atsushi Kumamoto6, Ayako Matsuoka, Yukinaga Miyashita7, Yoshizumi Miyoshi4, I. Shinohara, Mariko Teramoto4, Jeremy Faden, Alexa Halford8, Matthew D. McCarthy9, Robyn Millan10, John Sample11, David M. Smith12, L. A. Woodger10, Arnaud Masson, A. A. Narock3, Kazushi Asamura, T. F. Chang4, C. Y. Chiang13, Yoichi Kazama14, Kunihiro Keika15, S. Matsuda4, Tomonori Segawa4, Kanako Seki15, Masafumi Shoji4, Sunny W. Y. Tam13, Norio Umemura4, B. J. Wang14, B. J. Wang16, Shiang-Yu Wang14, Robert J. Redmon17, Juan V. Rodriguez18, Juan V. Rodriguez17, Howard J. Singer17, Jon Vandegriff19, S. Abe20, Masahito Nose21, Masahito Nose4, Atsuki Shinbori4, Yoshimasa Tanaka22, S. UeNo21, L. Andersson23, P. Dunn2, Christopher M. Fowler23, Jasper Halekas24, Takuya Hara2, Yuki Harada21, Christina O. Lee2, Robert Lillis2, David L. Mitchell2, Matthew R. Argall25, Kenneth R. Bromund3, James L. Burch26, Ian J. Cohen19, Michael Galloy27, Barbara L. Giles3, Allison Jaynes24, O. Le Contel28, Mitsuo Oka2, T. D. Phan2, Brian Walsh29, Joseph Westlake19, Frederick Wilder23, Stuart D. Bale2, Roberto Livi2, Marc Pulupa2, Phyllis Whittlesey2, A. DeWolfe23, Bryan Harter23, E. Lucas23, U. Auster30, John W. Bonnell2, Christopher Cully31, Eric Donovan31, Robert E. Ergun23, Harald U. Frey2, Brian Jackel31, A. Keiling2, Haje Korth19, J. P. McFadden2, Yukitoshi Nishimura29, Ferdinand Plaschke32, P. Robert28, Drew Turner8, James M. Weygand1, Robert M. Candey3, R. C. Johnson3, T. Kovalick3, M. H. Liu3, R. E. McGuire3, Aaron Breneman33, Kris Kersten33, P. Schroeder2 
TL;DR: The SPEDAS development history, goals, and current implementation are reviewed, and its “modes of use” are explained with examples geared for users and its technical implementation and requirements with software developers in mind are outlined.
Abstract: With the advent of the Heliophysics/Geospace System Observatory (H/GSO), a complement of multi-spacecraft missions and ground-based observatories to study the space environment, data retrieval, analysis, and visualization of space physics data can be daunting. The Space Physics Environment Data Analysis System (SPEDAS), a grass-roots software development platform ( www.spedas.org ), is now officially supported by NASA Heliophysics as part of its data environment infrastructure. It serves more than a dozen space missions and ground observatories and can integrate the full complement of past and upcoming space physics missions with minimal resources, following clear, simple, and well-proven guidelines. Free, modular and configurable to the needs of individual missions, it works in both command-line (ideal for experienced users) and Graphical User Interface (GUI) mode (reducing the learning curve for first-time users). Both options have “crib-sheets,” user-command sequences in ASCII format that can facilitate record-and-repeat actions, especially for complex operations and plotting. Crib-sheets enhance scientific interactions, as users can move rapidly and accurately from exchanges of technical information on data processing to efficient discussions regarding data interpretation and science. SPEDAS can readily query and ingest all International Solar Terrestrial Physics (ISTP)-compatible products from the Space Physics Data Facility (SPDF), enabling access to a vast collection of historic and current mission data. The planned incorporation of Heliophysics Application Programmer’s Interface (HAPI) standards will facilitate data ingestion from distributed datasets that adhere to these standards. Although SPEDAS is currently Interactive Data Language (IDL)-based (and interfaces to Java-based tools such as Autoplot), efforts are under-way to expand it further to work with python (first as an interface tool and potentially even receiving an under-the-hood replacement). We review the SPEDAS development history, goals, and current implementation. We explain its “modes of use” with examples geared for users and outline its technical implementation and requirements with software developers in mind. We also describe SPEDAS personnel and software management, interfaces with other organizations, resources and support structure available to the community, and future development plans.

Journal ArticleDOI
13 Jun 2019-Cell
TL;DR: This work systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique Gα subunit C termini, and identified sequence-based coupling specificity features, inside and outside the transmembrane domain, which were used to develop a coupling predictor that outperforms previous methods.

Journal ArticleDOI
TL;DR: This paper surveys the networking and communication technologies in autonomous driving from two aspects: intra- and inter-vehicle.
Abstract: The development of light detection and ranging, Radar, camera, and other advanced sensor technologies inaugurated a new era in autonomous driving. However, due to the intrinsic limitations of these sensors, autonomous vehicles are prone to making erroneous decisions and causing serious disasters. At this point, networking and communication technologies can greatly make up for sensor deficiencies, and are more reliable, feasible and efficient to promote the information interaction, thereby improving autonomous vehicle’s perception and planning capabilities as well as realizing better vehicle control. This paper surveys the networking and communication technologies in autonomous driving from two aspects: intra- and inter-vehicle. The intra-vehicle network as the basis of realizing autonomous driving connects the on-board electronic parts. The inter-vehicle network is the medium for interaction between vehicles and outside information. In addition, we present the new trends of communication technologies in autonomous driving, as well as investigate the current mainstream verification methods and emphasize the challenges and open issues of networking and communications in autonomous driving.

Journal ArticleDOI
TL;DR: In this paper, a deep learning-enabled mmWave massive MIMO framework for effective hybrid precoding is proposed, in which each selection of the precoders for obtaining the optimized decoder is regarded as a mapping relation in the deep neural network (DNN).
Abstract: Millimeter wave (mmWave) massive multiple-input multiple-output (MIMO) has been regarded to be an emerging solution for the next generation of communications, in which hybrid analog and digital precoding is an important method for reducing the hardware complexity and energy consumption associated with mixed signal components. However, the fundamental limitations of the existing hybrid precoding schemes is that they have high computational complexity and fail to fully exploit the spatial information. To overcome these limitations, this paper proposes, a deep-learning-enabled mmWave massive MIMO framework for effective hybrid precoding, in which each selection of the precoders for obtaining the optimized decoder is regarded as a mapping relation in the deep neural network (DNN). Specifically, the hybrid precoder is selected through training based on the DNN for optimizing precoding process of the mmWave massive MIMO. Additionally, we present extensive simulation results to validate the excellent performance of the proposed scheme. The results exhibit that the DNN-based approach is capable ofminimizing the bit error ratio (BER) and enhancing spectrum efficiency of the mmWave massive MIMO, which achieves better performance in hybrid precoding compared with conventional schemes while substantially reducing the required computational complexity.

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Seiji Sugita1, Seiji Sugita2, Rie Honda3, Tomokatsu Morota4, Shingo Kameda5, Hirotaka Sawada6, Eri Tatsumi2, Manabu Yamada1, C. Honda7, Yasuhiro Yokota3, Yasuhiro Yokota6, Toru Kouyama8, Naoya Sakatani6, K. Ogawa9, H. Suzuki10, Tatsuaki Okada2, Tatsuaki Okada6, Noriyuki Namiki11, Satoshi Tanaka11, Satoshi Tanaka6, Yuichi Iijima6, Kosuke Yoshioka2, Masahiro Hayakawa6, Yuichiro Cho2, Moe Matsuoka6, Naru Hirata7, Hideaki Miyamoto2, Deborah L. Domingue12, Masatoshi Hirabayashi13, Tomoki Nakamura14, Takahiro Hiroi15, Tatsuhiro Michikami16, Patrick Michel17, Ronald-Louis Ballouz6, Ronald-Louis Ballouz18, Olivier S. Barnouin19, Carolyn M. Ernst19, Stefan Schröder20, Hideaki Kikuchi2, Ryodo Hemmi2, Goro Komatsu1, Goro Komatsu12, T. Fukuhara5, Makoto Taguchi5, Takehiko Arai, Hiroki Senshu1, Hirohide Demura7, Yoshiko Ogawa7, Yuri Shimaki6, Tomohiko Sekiguchi21, T. G. Müller22, Axel Hagermann23, Takahide Mizuno6, Hirotomo Noda, Koji Matsumoto11, R. Yamada7, Yoshiaki Ishihara6, H. Ikeda, Hiroshi Araki, K. Yamamoto, Shinsuke Abe24, Fumi Yoshida1, A. Higuchi, Sho Sasaki25, S. Oshigami, Seiitsu Tsuruta, Kazuyoshi Asari, Seiichi Tazawa, M. Shizugami, J. Kimura25, Toshimichi Otsubo26, Hikaru Yabuta27, Sunao Hasegawa6, Masateru Ishiguro28, Shogo Tachibana2, Eric Palmer12, Robert Gaskell12, L. Le Corre12, Ralf Jaumann20, Katharina A. Otto20, Nicole Schmitz20, Paul A. Abell, M. A. Barucci29, Michael E. Zolensky, Faith Vilas12, Florian Thuillet17, C. Sugimoto2, N. Takaki2, Yutaka Suzuki2, Hiroaki Kamiyoshihara2, Masato Okada2, Kenji Nagata8, Masaki Fujimoto6, Makoto Yoshikawa11, Makoto Yoshikawa6, Yukio Yamamoto6, Yukio Yamamoto11, Kei Shirai6, Rina Noguchi6, Naoko Ogawa6, Fuyuto Terui6, Shota Kikuchi6, Tomohiro Yamaguchi6, Yusuke Oki2, Yuki Takao2, Hiroshi Takeuchi6, Go Ono, Yuya Mimasu6, Kent Yoshikawa, T. Takahashi6, Yuto Takei6, Atsushi Fujii6, Chikako Hirose, Satoru Nakazawa6, Satoshi Hosoda6, Osamu Mori6, Takanobu Shimada6, Stefania Soldini6, Takahiro Iwata6, Takahiro Iwata11, Masanao Abe11, Masanao Abe6, Hajime Yano6, Hajime Yano11, Ryudo Tsukizaki6, M. Ozaki11, M. Ozaki6, Kazutaka Nishiyama6, Takanao Saiki6, Sei-ichiro Watanabe4, Sei-ichiro Watanabe6, Yoshiyuki Tsuda11, Yoshiyuki Tsuda6 
19 Apr 2019-Science
TL;DR: Spectral observations and a principal components analysis suggest that Ryugu originates from the Eulalia or Polana asteroid family in the inner main belt, possibly via more than one generation of parent bodies.
Abstract: Additional co-authors: N Namiki, S Tanaka, Y Iijima, K Yoshioka, M Hayakawa, Y Cho, M Matsuoka, N Hirata, N Hirata, H Miyamoto, D Domingue, M Hirabayashi, T Nakamura, T Hiroi, T Michikami, P Michel, R-L Ballouz, O S Barnouin, C M Ernst, S E Schroder, H Kikuchi, R Hemmi, G Komatsu, T Fukuhara, M Taguchi, T Arai, H Senshu, H Demura, Y Ogawa, Y Shimaki, T Sekiguchi, T G Muller, T Mizuno, H Noda, K Matsumoto, R Yamada, Y Ishihara, H Ikeda, H Araki, K Yamamoto, S Abe, F Yoshida, A Higuchi, S Sasaki, S Oshigami, S Tsuruta, K Asari, S Tazawa, M Shizugami, J Kimura, T Otsubo, H Yabuta, S Hasegawa, M Ishiguro, S Tachibana, E Palmer, R Gaskell, L Le Corre, R Jaumann, K Otto, N Schmitz, P A Abell, M A Barucci, M E Zolensky, F Vilas, F Thuillet, C Sugimoto, N Takaki, Y Suzuki, H Kamiyoshihara, M Okada, K Nagata, M Fujimoto, M Yoshikawa, Y Yamamoto, K Shirai, R Noguchi, N Ogawa, F Terui, S Kikuchi, T Yamaguchi, Y Oki, Y Takao, H Takeuchi, G Ono, Y Mimasu, K Yoshikawa, T Takahashi, Y Takei, A Fujii, C Hirose, S Nakazawa, S Hosoda, O Mori, T Shimada, S Soldini, T Iwata, M Abe, H Yano, R Tsukizaki, M Ozaki, K Nishiyama, T Saiki, S Watanabe, Y Tsuda

Journal ArticleDOI
TL;DR: A randomized, controlled trial has begun to compare neoadjuvant chemotherapy using gemcitabine and S-1 with upfront surgery for patients planned resection of pancreatic cancer.
Abstract: A randomized, controlled trial has begun to compare neoadjuvant chemotherapy using gemcitabine and S-1 with upfront surgery for patients planned resection of pancreatic cancer. Patients were enrolled after the diagnosis of resectable or borderline resectable by portal vein involvement pancreatic cancer with histological confirmation. They were randomly assigned to either neoadjuvant chemotherapy or upfront surgery. Adjuvant chemotherapy using S-1 was administered for 6 months to patients with curative resection who fully recovered within 10 weeks after surgery in both arms. The primary endpoint is overall survival; secondary endpoints include adverse events, resection rate, recurrence-free survival, residual tumor status, nodal metastases and tumor marker kinetics. The target sample size was required to be at least 163 (alpha-error 0.05; power 0.8) in both arms. A total of 360 patients were required after considering ineligible cases. This trial began in January 2013 and was registered with the UMIN Clinical Trials Registry (UMIN000009634).

Journal ArticleDOI
01 Sep 2019-Nature
TL;DR: A proof-of-concept experiment for probabilistic computing using spintronics technology, and integer factorization, an illustrative example of the optimization class of problems addressed by adiabatic9 and gated2 quantum computing, is presented.
Abstract: Conventional computers operate deterministically using strings of zeros and ones called bits to represent information in binary code. Despite the evolution of conventional computers into sophisticated machines, there are many classes of problems that they cannot efficiently address, including inference, invertible logic, sampling and optimization, leading to considerable interest in alternative computing schemes. Quantum computing, which uses qubits to represent a superposition of 0 and 1, is expected to perform these tasks efficiently1–3. However, decoherence and the current requirement for cryogenic operation4, as well as the limited many-body interactions that can be implemented, pose considerable challenges. Probabilistic computing1,5–7 is another unconventional computation scheme that shares similar concepts with quantum computing but is not limited by the above challenges. The key role is played by a probabilistic bit (a p-bit)—a robust, classical entity fluctuating in time between 0 and 1, which interacts with other p-bits in the same system using principles inspired by neural networks8. Here we present a proof-of-concept experiment for probabilistic computing using spintronics technology, and demonstrate integer factorization, an illustrative example of the optimization class of problems addressed by adiabatic9 and gated2 quantum computing. Nanoscale magnetic tunnel junctions showing stochastic behaviour are developed by modifying market-ready magnetoresistive random-access memory technology10,11 and are used to implement three-terminal p-bits that operate at room temperature. The p-bits are electrically connected to form a functional asynchronous network, to which a modified adiabatic quantum computing algorithm that implements three- and four-body interactions is applied. Factorization of integers up to 945 is demonstrated with this rudimentary asynchronous probabilistic computer using eight correlated p-bits, and the results show good agreement with theoretical predictions, thus providing a potentially scalable hardware approach to the difficult problems of optimization and sampling. A probabilistic computer utilizing probabilistic bits, or p-bits, is implemented with stochastic nanomagnetic devices in a neural-network-inspired electrical circuit operating at room temperature and demonstrates integer factorization up to 945.

Journal ArticleDOI
TL;DR: In this article, a precipitation-strengthened FeCoNiCrTi0.2 high-entropy alloy strengthened by two types of coherent nano-precipitates but with the same composition was fabricated, and its tensile properties at room and cryogenic temperatures (77 K) and the corresponding defect-structure evolution were investigated.

Journal ArticleDOI
TL;DR: This document is an English version of JCS 2018 Guideline on Diagnosis and Treatment of Acute Coronary Syndrome reported at the Japanese Circulation Society Joint Working Groups performed in 2018.
Abstract: J-STAGE Advance Publication released online March 29, 2019 Mailing address: Scientific Committee of the Japanese Circulation Society, 18F Imperial Hotel Tower, 1-1-1 Uchisaiwai-cho, Chiyoda-ku, Tokyo 100-0011, Japan. E-mail: meeting@j-circ.or.jp This document is an English version of JCS 2018 Guideline on Diagnosis and Treatment of Acute Coronary Syndrome reported at the Japanese Circulation Society Joint Working Groups performed in 2018. (Website: http://www.j-circ.or.jp/guideline/pdf/JCS2018_ kimura.pdf). *Chairperson. Refer to Appendix 1 for the details of members. Joint Working Groups: The Japanese Circulation Society, the Japanese Association for Thoracic Surgery, the Japanese Association of Cardiac Rehabilitation, the Japanese Association of Cardiovascular Intervention and Therapeutics, the Japanese College of Cardiology, the Japanese Coronary Association, the Japanese Heart Rhythm Society, the Japanese Society for Cardiovascular Surgery, the Japanese Society of Intensive Care Medicine ISSN-1346-9843 All rights are reserved to the Japanese Circulation Society. For permissions, please e-mail: cj@j-circ.or.jp JCS 2018 Guideline on Diagnosis and Treatment of Acute Coronary Syndrome