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1,559 results on '"Oshima, H"'

1. Isotropy of cosmic rays beyond $10^{20}$ eV favors their heavy mass composition

Author

Telescope Array Collaboration, Abbasi, R. U., Abe, Y., Abu-Zayyad, T., Allen, M., Arai, Y., Arimura, R., Barcikowski, E., Belz, J. W., Bergman, D. R., Blake, S. A., Buckland, I., Cheon, B. G., Chikawa, M., Fujii, T., Fujisue, K., Fujita, K., Fujiwara, R., Fukushima, M., Furlich, G., Globus, N., Gonzalez, R., Hanlon, W., Hayashida, N., He, H., Hibi, R., Hibino, K., Higuchi, R., Honda, K., Ikeda, D., Inoue, N., Ishii, T., Ito, H., Ivanov, D., Iwasaki, A., Jeong, H. M., Jeong, S., Jui, C. C. H., Kadota, K., Kakimoto, F., Kalashev, O., Kasahara, K., Kasami, S., Kawakami, S., Kawata, K., Kharuk, I., Kido, E., Kim, H. B., Kim, J. H., Kim, S. W., Kimura, Y., Komae, I., Kuzmin, V., Kuznetsov, M., Kwon, Y. J., Lee, K. H., Lubsandorzhiev, B., Lundquist, J. P., Matsumiya, H., Matsuyama, T., Matthews, J. N., Mayta, R., Mizuno, K., Murakami, M., Myers, I., Nagataki, S., Nakai, K., Nakamura, T., Nishio, E., Nonaka, T., Oda, H., Ogio, S., Onishi, M., Ohoka, H., Okazaki, N., Oku, Y., Okuda, T., Omura, Y., Ono, M., Oshima, A., Oshima, H., Ozawa, S., Park, I. H., Park, K. Y., Potts, M., Pshirkov, M. S., Remington, J., Rodriguez, D. C., Rott, C., Rubtsov, G. I., Ryu, D., Sagawa, H., Saito, R., Sakaki, N., Sako, T., Sakurai, N., Sato, D., Sato, K., Sato, S., Sekino, K., Shah, P. D., Shibata, N., Shibata, T., Shikita, J., Shimodaira, H., Shin, B. K., Shin, H. S., Shinto, D., Smith, J. D., Sokolsky, P., Stokes, B. T., Stroman, T. A., Takagi, Y., Takahashi, K., Takamura, M., Takeda, M., Takeishi, R., Taketa, A., Takita, M., Tameda, Y., Tanaka, K., Tanaka, M., Tanoue, Y., Thomas, S. B., Thomson, G. B., Tinyakov, P., Tkachev, I., Tokuno, H., Tomida, T., Troitsky, S., Tsuda, R., Tsunesada, Y., Udo, S., Urban, F., Warren, D., Wong, T., Yamazaki, K., Yashiro, K., Yoshida, F., Zhezher, Y., and Zundel, Z.

Subjects
Astrophysics - High Energy Astrophysical Phenomena
Abstract

We report an estimation of the injected mass composition of ultra-high energy cosmic rays (UHECRs) at energies higher than 10 EeV. The composition is inferred from an energy-dependent sky distribution of UHECR events observed by the Telescope Array surface detector by comparing it to the Large Scale Structure of the local Universe. In the case of negligible extra-galactic magnetic fields the results are consistent with a relatively heavy injected composition at E ~ 10 EeV that becomes lighter up to E ~ 100 EeV, while the composition at E > 100 EeV is very heavy. The latter is true even in the presence of highest experimentally allowed extra-galactic magnetic fields, while the composition at lower energies can be light if a strong EGMF is present. The effect of the uncertainty in the galactic magnetic field on these results is subdominant., Comment: 8 pages, 3 figures, accepted for publication in PRL

Published
2024

2. Mass composition of ultra-high energy cosmic rays from distribution of their arrival directions with the Telescope Array

Author

Telescope Array Collaboration, Abbasi, R. U., Abe, Y., Abu-Zayyad, T., Allen, M., Arai, Y., Arimura, R., Barcikowski, E., Belz, J. W., Bergman, D. R., Blake, S. A., Buckland, I., Cheon, B. G., Chikawa, M., Fujii, T., Fujisue, K., Fujita, K., Fujiwara, R., Fukushima, M., Furlich, G., Globus, N., Gonzalez, R., Hanlon, W., Hayashida, N., He, H., Hibi, R., Hibino, K., Higuchi, R., Honda, K., Ikeda, D., Inoue, N., Ishii, T., Ito, H., Ivanov, D., Iwasaki, A., Jeong, H. M., Jeong, S., Jui, C. C. H., Kadota, K., Kakimoto, F., Kalashev, O., Kasahara, K., Kasami, S., Kawakami, S., Kawata, K., Kharuk, I., Kido, E., Kim, H. B., Kim, J. H., Kim, S. W., Kimura, Y., Komae, I., Kuzmin, V., Kuznetsov, M., Kwon, Y. J., Lee, K. H., Lubsandorzhiev, B., Lundquist, J. P., Matsumiya, H., Matsuyama, T., Matthews, J. N., Mayta, R., Mizuno, K., Murakami, M., Myers, I., Nagataki, S., Nakai, K., Nakamura, T., Nishio, E., Nonaka, T., Oda, H., Ogio, S., Onishi, M., Ohoka, H., Okazaki, N., Oku, Y., Okuda, T., Omura, Y., Ono, M., Oshima, A., Oshima, H., Ozawa, S., Park, I. H., Park, K. Y., Potts, M., Pshirkov, M. S., Remington, J., Rodriguez, D. C., Rott, C., Rubtsov, G. I., Ryu, D., Sagawa, H., Saito, R., Sakaki, N., Sako, T., Sakurai, N., Sato, D., Sato, K., Sato, S., Sekino, K., Shah, P. D., Shibata, N., Shibata, T., Shikita, J., Shimodaira, H., Shin, B. K., Shin, H. S., Shinto, D., Smith, J. D., Sokolsky, P., Stokes, B. T., Stroman, T. A., Takagi, Y., Takahashi, K., Takamura, M., Takeda, M., Takeishi, R., Taketa, A., Takita, M., Tameda, Y., Tanaka, K., Tanaka, M., Tanoue, Y., Thomas, S. B., Thomson, G. B., Tinyakov, P., Tkachev, I., Tokuno, H., Tomida, T., Troitsky, S., Tsuda, R., Tsunesada, Y., Udo, S., Urban, F., Warren, D., Wong, T., Yamazaki, K., Yashiro, K., Yoshida, F., Zhezher, Y., and Zundel, Z.

Subjects
Astrophysics - High Energy Astrophysical Phenomena
Abstract

We use a new method to estimate the injected mass composition of ultrahigh cosmic rays (UHECRs) at energies higher than 10 EeV. The method is based on comparison of the energy-dependent distribution of cosmic ray arrival directions as measured by the Telescope Array experiment (TA) with that calculated in a given putative model of UHECR under the assumption that sources trace the large-scale structure (LSS) of the Universe. As we report in the companion letter, the TA data show large deflections with respect to the LSS which can be explained, assuming small extra-galactic magnetic fields (EGMF), by an intermediate composition changing to a heavy one (iron) in the highest energy bin. Here we show that these results are robust to uncertainties in UHECR injection spectra, the energy scale of the experiment and galactic magnetic fields (GMF). The assumption of weak EGMF, however, strongly affects this interpretation at all but the highest energies E > 100 EeV, where the remarkable isotropy of the data implies a heavy injected composition even in the case of strong EGMF. This result also holds if UHECR sources are as rare as $2 \times 10^{-5}$ Mpc$^{-3}$, that is the conservative lower limit for the source number density., Comment: 18 pages, 11 figures, accepted for publication in PRD

Published
2024

3. Observation of Declination Dependence in the Cosmic Ray Energy Spectrum

Author

The Telescope Array Collaboration, Abbasi, R. U., Abu-Zayyad, T., Allen, M., Belz, J. W., Bergman, D. R., Buckland, I., Campbell, W., Cheon, B. G., Endo, K., Fedynitch, A., Fujii, T., Fujisue, K., Fujita, K., Fukushima, M., Furlich, G., Gerber, Z., Globus, N., Hanlon, W., Hayashida, N., He, H., Hibino, K., Higuchi, R., Ikeda, D., Ishii, T., Ivanov, D., Jeong, S., Jui, C. C. H., Kadota, K., Kakimoto, F., Kalashev, O., Kasahara, K., Kawachi, Y., Kawata, K., Kharuk, I., Kido, E., Kim, H. B., Kim, J. H., Kim, S. W., Kobo, R., Komae, I., Komatsu, K., Komori, K., Koyama, C., Kudenko, M., Kuroiwa, M., Kusumori, Y., Kuznetsov, M., Kwon, Y. J., Lee, K. H., Lee, M. J., Lubsandorzhiev, B., Lundquist, J. P., Matsuzawa, A., Matthews, J. A., Matthews, J. N., Mizuno, K., Mori, M., Murakami, M., Nagataki, S., Nakahara, M., Nakamura, T., Nakayama, T., Nakayama, Y., Nonaka, T., Ogio, S., Ohoka, H., Okazaki, N., Onishi, M., Oshima, A., Oshima, H., Ozawa, S., Park, I. H., Park, K. Y., Potts, M., Przybylak, M., Pshirkov, M. S., Remington, J., Rott, C., Rubtsov, G. I., Ryu, D., Sagawa, H., Sakaki, N., Sakamoto, R., Sako, T., Sakurai, N., Sakurai, S., Sato, D., Sato, S., Sekino, K., Shibata, T., Shikita, J., Shimodaira, H., Shin, B. K., Shin, H. S., Shinozaki, K., Smith, J. D., Sokolsky, P., Stokes, B. T., Stroman, T. A., Takagi, Y., Takahashi, K., Takeda, M., Takeishi, R., Taketa, A., Takita, M., Tameda, Y., Tanaka, K., Tanaka, M., Thomas, S. B., Thomson, G. B., Tinyakov, P., Tkachev, I., Tomida, T., Troitsky, S., Tsunesada, Y., Udo, S., Urban, F., Vaiman, I. A., Vrábel, M., Warren, D., Yamazaki, K., Zhezher, Y., Zundel, Z., and Zvirzdin, J.

Subjects
Astrophysics - High Energy Astrophysical Phenomena
Abstract

We report on an observation of the difference between northern and southern skies of the ultrahigh energy cosmic ray energy spectrum with a significance of ${\sim}8\sigma$. We use measurements from the two largest experiments$\unicode{x2014}$the Telescope Array observing the northern hemisphere and the Pierre Auger Observatory viewing the southern hemisphere. Since the comparison of two measurements from different observatories introduces the issue of possible systematic differences between detectors and analyses, we validate the methodology of the comparison by examining the region of the sky where the apertures of the two observatories overlap. Although the spectra differ in this region, we find that there is only a $1.8\sigma$ difference between the spectrum measurements when anisotropic regions are removed and a fiducial cut in the aperture is applied., Comment: 8 pages, 6 figures

Published
2024

4. Measurements of protons and charged pions emitted from $\nu_{\mu}$ charged-current interactions on iron at a mean neutrino energy of 1.49$\,$GeV using a nuclear emulsion detector

Author

Oshima, H., Matsuo, T., Ali, A., Aoki, S., Berns, L., Fukuda, T., Hanaoka, Y., Hayato, Y., Hiramoto, A., Ichikawa, A. K., Inamoto, H., Kasumi, A., Kawahara, H., Kikawa, T., Komatani, R., Komatsu, M., Kuretsubo, K., Marushima, T., Matsumoto, H., Mikado, S., Minamino, A., Mizuno, K., Morimoto, Y., Morishima, K., Naganawa, N., Naiki, M., Nakamura, M., Nakamura, Y., Nakano, T., Nakaya, T., Nishio, A., Odagawa, T., Ogawa, S., Rokujo, H., Sato, O., Shibuya, H., Sugimura, K., Suzui, L., Suzuki, Y., Takagi, H., Takahashi, S., Takao, T., Tanihara, Y., Watanabe, M., Yamada, K., Yasutome, K., Yokoyama, M., and Yoshimoto, M.

Subjects
High Energy Physics - Experiment
Abstract

This study conducted an analysis of muons, protons, and charged pions emitted from $\nu_{\mu}$ charged-current interactions on iron using a nuclear emulsion detector. The emulsion detector with a 65$\,$kg iron target was exposed to a neutrino beam corresponding to 4.0$\times$10$^{19}$ protons on target with a mean neutrino energy of 1.49$\,$GeV. The measurements were performed at a momentum threshold of 200 (50)$\,$MeV/$c$ for protons (pions), which are the lowest momentum thresholds attempted up to now. The measured quantities are the multiplicities, emission angles, and momenta of the muons, protons, and charged pions. In addition to these inclusive measurements, exclusive measurements such as the muon-proton emission-angle correlations of specific channels and the opening angle between the protons of CC0$\pi$2$p$ events were performed. The data were compared to Monte Carlo (MC) predictions and some significant differences were observed. The results of the study demonstrate the capability of detailed measurements of neutrino-nucleus interactions using a nuclear emulsion detector to improve neutrino interaction models., Comment: 21 pages, 25 figures

Published
2022
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5. First measurement using a nuclear emulsion detector of the $\nu_{\mu}$ charged-current cross section on iron around the 1$\,$GeV energy region

Author

Oshima, H., Matsuo, T., Ali, A., Aoki, S., Berns, L., Fukuda, T., Hanaoka, Y., Hayato, Y., Hiramoto, A., Ichikawa, A. K., Kawahara, H., Kikawa, T., Komatani, R., Komatsu, M., Kuretsubo, K., Marushima, T., Matsumoto, H., Mikado, S., Minamino, A., Mizuno, K., Morimoto, Y., Morishima, K., Naganawa, N., Naiki, M., Nakamura, M., Nakamura, Y., Nakano, N., Nakano, T., Nakaya, T., Nishio, A., Odagawa, T., Ogawa, S., Rokujo, H., Sato, O., Shibuya, H., Sugimura, K., Suzui, L., Suzuki, Y., Takagi, H., Takahashi, S., Takao, T., Tanihara, Y., Watanabe, R., Yamada, K., Yasutome, K., and Yokoyama, M.

Subjects
High Energy Physics - Experiment
Abstract

We have carried out $\nu_{\mu}$ charged-current interaction measurement on iron using an emulsion detector exposed to the T2K neutrino beam in the J-PARC neutrino facility. The data samples correspond to 4.0$\times$10$^{19}$ protons on target, and the neutrino mean energy is 1.49$\,$GeV. The emulsion detector is suitable for precision measurements of charged particles produced in neutrino-iron interactions with a low momentum threshold thanks to thin-layered structure and sub-$\mu$m spatial resolution. The charged particles are successfully detected, and their multiplicities are measured using the emulsion detector. The cross section was measured to be $\sigma^{\mathrm{Fe}}_{\mathrm{CC}} = (1.28 \pm 0.11({\mathrm{stat.}})^{+0.12}_{-0.11}({\mathrm{syst.}})) \times 10^{-38} \, {\mathrm{cm}}^{2}/{\mathrm{nucleon}}$. The cross section in a limited kinematic phase space of induced muons, $\theta_{\mu} < 45^{\circ}$ and $p_{\mu} > 400 \, {\rm MeV}/c$, on iron was $\sigma^{\mathrm{Fe}}_{\mathrm{CC \hspace{1mm} phase \hspace{0.5mm} space}} = (0.84 \pm 0.07({\mathrm{stat.}})^{+0.07}_{-0.06}({\mathrm{syst.}})) \times 10^{-38} \, {\mathrm{cm}}^{2}/{\mathrm{nucleon}}$. The cross-section results are consistent with previous values obtained via different techniques using the same beamline, and they are well reproduced by current neutrino interaction models. These results demonstrate the capability of the detector towards the detailed measurements of the neutrino-nucleus interactions around the 1$\,$GeV energy region., Comment: 27 pages, 17 figures

Published
2020
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6. First measurement of $\bar{\nu}_{\mu}$ and $\nu_{\mu}$ charged-current inclusive interactions on water using a nuclear emulsion detector

Author

Hiramoto, A., Suzuki, Y., Ali, A., Aoki, S., Berns, L., Fukuda, T., Hanaoka, Y., Hayato, Y., Ichikawa, A. K., Kawahara, H., Kikawa, T., Koga, T., Komatani, R., Komatsu, M., Kosakai, Y., Matsuo, T., Mikado, S., Minamino, A., Mizuno, K., Morimoto, Y., Morishima, K., Naganawa, N., Naiki, M., Nakamura, M., Nakamura, Y., Nakano, N., Nakano, T., Nakaya, T., Nishio, A., Odagawa, T., Ogawa, S., Oshima, H., Rokujo, H., Sanjana, I., Sato, O., Shibuya, H., Sugimura, K., Suzui, L., Takagi, H., Takao, T., Tanihara, Y., Yasutome, K., and Yokoyama, M.

Subjects
High Energy Physics - Experiment, Physics - Instrumentation and Detectors
Abstract

This paper reports the track multiplicity and kinematics of muons, charged pions, and protons from charged-current inclusive $\bar{\nu}_{\mu}$ and $\nu_{\mu}$ interactions on a water target, measured using a nuclear emulsion detector in the NINJA experiment. A 3-kg water target was exposed to the T2K antineutrino-enhanced beam with a mean energy of 1.3 GeV. Owing to the high-granularity of the nuclear emulsion, protons with momenta down to 200 MeV/$c$ from the neutrino-water interactions were detected. We find good agreement between the observed data and model predictions for all kinematic distributions other than the number of charged pions. These results demonstrate the capability of measurements with nuclear emulsion to improve neutrino interaction models., Comment: 22 pages, 20 figures

Published
2020
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7. The energy spectrum of cosmic rays measured by the Telescope Array using 10 years of fluorescence detector data

Author

Abbasi, R.U., Abe, Y., Abu-Zayyad, T., Allen, M., Arai, Y., Arimura, R., Barcikowski, E., Belz, J.W., Bergman, D.R., Blake, S.A., Buckland, I., Cheon, B.G., Chikawa, M., Fedynitch, A., Fujii, T., Fujisue, K., Fujita, K., Fujiwara, R., Fukushima, M., Furlich, G., Gerber, Z., Globus, N., Hanlon, W., Hayashida, N., He, H., Hibi, R., Hibino, K., Higuchi, R., Honda, K., Ikeda, D., Inoue, N., Ishii, T., Ito, H., Ivanov, D., Iwasaki, A., Jeong, H.M., Jeong, S., Jui, C.C.H., Kadota, K., Kakimoto, F., Kalashev, O., Kasahara, K., Kasami, S., Kawakami, S., Kawata, K., Kharuk, I., Kido, E., Kim, H.B., Kim, J.H., Kim, S.W., Kimura, Y., Komae, I., Komori, K., Kusumori, Y., Kuznetsov, M., Kwon, Y.J., Lee, K.H., Lee, M.J., Lubsandorzhiev, B., Lundquist, J.P., Matsuyama, T., Matthews, J.A., Matthews, J.N., Mayta, R., Miyashita, K., Mizuno, K., Mori, M., Murakami, M., Myers, I., Nagataki, S., Nakai, K., Nakamura, T., Nishio, E., Nonaka, T., Ogio, S., Ohoka, H., Okazaki, N., Oku, Y., Okuda, T., Omura, Y., Onishi, M., Ono, M., Oshima, A., Oshima, H., Ozawa, S., Park, I.H., Park, K.Y., Potts, M., Pshirkov, M.S., Remington, J., Rodriguez, D.C., Rott, C., Rubtsov, G.I., Ryu, D., Sagawa, H., Saito, R., Sakaki, N., Sako, T., Sakurai, N., Sato, D., Sato, K., Sato, S., Sekino, K., Shah, P.D., Shibata, N., Shibata, T., Shikita, J., Shimodaira, H., Shin, B.K., Shin, H.S., Shinto, D., Smith, J.D., Sokolsky, P., Stokes, B.T., Stroman, T.A., Takagi, Y., Takahashi, K., Takamura, M., Takeda, M., Takeishi, R., Taketa, A., Takita, M., Tameda, Y., Tanaka, K., Tanaka, M., Thomas, S.B., Thomson, G.B., Tinyakov, P., Tkachev, I., Tokuno, H., Tomida, T., Troitsky, S., Tsuda, R., Tsunesada, Y., Udo, S., Urban, F., Vaiman, I.A., Warren, D., Wong, T., Yamazaki, K., Yashiro, K., Yoshida, F., Zhezher, Y., and Zundel, Z.

Published
2023
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8. Renal Recovery for Patients with ANCA-Associated Vasculitis and Low eGFR in the ADVOCATE Trial of Avacopan

Author

Peh, C. Au, Chakera, A., Cooper, B., Kurtkoti, J., Langguth, D., Levidiotis, V., Luxton, G., Mount, P., Mudge, D., Noble, E., Phoon, R., Ranganathan, D., Ritchie, A., Ryan, J., Suranyi, M., Rosenkranz, A., Lhotta, K., Kronbichler, A., Demoulin, N., Bovy, C., Hellemans, R., Hougardy, J., Sprangers, B., Wissing, K., Pagnoux, C., Barbour, S., Brachemi, S., Cournoyer, S., Girard, L., Laurin, L., Liang, P., Philibert, D., Walsh, M., Tesar, V., Becvar, R., Horak, P., Rychlik, I., Szpirt, W., Dieperink, H., Gregersen, J., Ivarsen, P., Krarup, E., Lyngsoe, C., Rigothier, C., Augusto, J., Belot, A., Chauveau, D., Cornec, D., Jourde-Chiche, N., Ficheux, M., Karras, A., Klein, A., Maurier, F., Mesbah, R., Moranne, O., Neel, A., Quemeneur, T., Saadoun, D., Terrier, B., Zaoui, P., Schaier, M., Benck, U., Bergner, R., Busch, M., Floege, J., Grundmann, F., Haller, H., Haubitz, M., Hellmich, B., Henes, J., Hohenstein, B., Hugo, C., Iking-Konert, C., Arndt, F., Kubacki, T., Kotter, I., Lamprecht, P., Lindner, T., Halbritter, J., Mehling, H., Schönermarck, U., Venhoff, N., Vielhauer, V., Witzke, O., Szombati, I., Szucs, G., Garibotto, G., Alberici, F., Brunetta, E., Dagna, L., De Vita, S., Emmi, G., Gabrielli, A., Manenti, L., Pieruzzi, F., Roccatello, D., Salvarani, C., Dobashi, H., Atsumi, T., Fujimoto, S., Hagino, N., Ihata, A., Kaname, S., Kaneko, Y., Katagiri, A., Katayama, M., Kirino, Y., Kitagawa, K., Komatsuda, A., Kono, H., Kurasawa, T., Matsumura, R., Mimura, T., Morinobu, A., Murakawa, Y., Naniwa, T., Nanki, T., Ogawa, N., Oshima, H., Sada, K., Sugiyama, E., Takeuchi, T., Taki, H., Tamura, N., Tsukamoto, T., Yamagata, K., Yamamura, M., van Daele, P., Rutgers, A., Teng, Y., Walker, R., Chua, I., Collins, M., Rabindranath, K., de Zoysa, J., Svensson, M., Grevbo, B., Kalstad, S., Little, M., Clarkson, M., Molloy, E., Pamplona, I. Agraz, Anton, J., Lucia, V. Barrio, Ciggaran, S., Cid, M. Cinta, Encarnacion, M. Diaz, Oliveras, X. Fulladosa, Soler, M. Jose, Rusinol, H. Marco, Praga, M., Porras, L. Quintana, Segarra, A., Bruchfeld, A., Segelmark, M., Soveri, I., Thomaidi, E., Westman, K., Neumann, T., Burnier, M., Daikeler, T., Dudler, J., Hauser, T., Seeger, H., Vogt, B., Jayne, D., Burton, J., Al Jayyousi, R., Amin, T., Andrews, J., Baines, L., Brogan, P., Dasgupta, B., Doulton, T., Flossmann, O., Griffin, S., Harper, J., Harper, L., Kidder, D., Klocke, R., Lanyon, P., Luqmani, R., McLaren, J., Makanjuola, D., McCann, L., Nandagudi, A., Selvan, S., O'Riordan, E., Patel, M., Patel, R., Pusey, C., Rajakariar, R., Robson, J., Robson, M., Salama, A., Smyth, L., Sznajd, J., Taylor, J., Merkel, P., Sreih, A., Belilos, E., Bomback, A., Carlin, J., Chen Lin, Y. Chang, Derebail, V., Dragoi, S., Dua, A., Forbess, L., Geetha, D., Gipson, P., Gohh, R., Greenwood, G.T., Hugenberg, S., Jimenez, R., Kaskas, M., Kermani, T., Kivitz, A., Koening, C., Langford, C., Marder, G., Mohamed, A., Monach, P., Neyra, N., Niemer, G., Niles, J., Obi, R., Owens, C., Parks, D., Podoll, A., Rovin, B., Sam, R., Shergy, W., Silva, A., Specks, U., Spiera, R., Springer, J., Striebich, C., Swarup, A., Thakar, S., Tiliakos, A., Tsai, Y., Waguespack, D., Wasko, M. Chester, Cortazar, Frank B., Niles, John L., Jayne, David R.W., Merkel, Peter A., Bruchfeld, Annette, Yue, Huibin, Schall, Thomas J., and Bekker, Pirow

Published
2023
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9. Pharmacokinetics and Safety of Single and Multiple Doses of Peficitinib (ASP015K) in Healthy Chinese Subjects

Author

Gao X, He X, Oshima H, Miyatake D, Otsuka Y, Kato K, Cai C, Wojtkowski T, Song N, Kaneko Y, and Shi A

Subjects
rheumatoid arthritis, treatment, dose-proportionality, tsdmards, Therapeutics. Pharmacology, RM1-950
Abstract

Xin Gao,1 Xuemei He,1 Hiroyuki Oshima,2 Daisuke Miyatake,2 Yukio Otsuka,2 Kota Kato,3 Chunxiao Cai,4 Tomasz Wojtkowski,5 Nan Song,6 Yuichiro Kaneko,7 Aixin Shi1 1Clinical Trial Center, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Clinical Pharmacology and Exploratory Development, Astellas Pharma Inc., Tokyo, Japan; 3Analysis & Pharmacokinetics Research Labs., Astellas Pharma Inc., Ibaraki, Japan; 4Development Medical Department, Astellas (China) Investment Co., Ltd, Beijing, People’s Republic of China; 5Data Science Development, Astellas Pharma US, Inc., Northbrook, IL, USA; 6Development Division Biostatistics and Statistical Programming, Astellas (China) Investment Co., Ltd, Beijing, People’s Republic of China; 7Biostatistics Group, Japan-Asia Data Science, Development, Astellas Pharma Inc, Tokyo, JapanCorrespondence: Aixin Shi, Clinical Trial Center, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Science, Beijing, 100730, People’s Republic of China, Tel +86-10-85133632, Email aixins0302@126.comObjective: To investigate the pharmacokinetics and safety of peficitinib (Janus kinase inhibitor for the treatment of rheumatoid arthritis) in healthy Chinese subjects following single and multiple doses.Methods: This open-label, randomized study was conducted at one site in China. Subjects received peficitinib 50, 100 or 150 mg as a single dose on Day 1 (fasted) and once daily from Days 8 to 13 in the multiple-dose period (fed). Blood samples were collected before administration each day, and up to 72h post administration. Pharmacokinetic assessments included area under the concentration curve (AUC), half-life (t1/2), maximum concentration (Cmax), and time to maximum concentration (tmax) of peficitinib and its metabolites (H1, H2 and H4). Treatment-emergent adverse events (TEAEs) were evaluated.Results: Thirty-six subjects were enrolled (12 per dose group). After a single dose of peficitinib, median tmax was 1.0– 1.5h and mean t1/2 was 7.4– 13.0h for all doses. In the multiple-dose period, median tmax was 1.5– 2.0h. Dose-proportional increases in Cmax and AUC24h were observed for peficitinib and its metabolites following single and multiple doses, with minimal drug accumulation. The major metabolite was H2, with a systemic exposure of > 150% of the parent AUC. Drug-related TEAEs were experienced by 5 (13.9%) and 12 (33.3%) subjects in the single- and multiple-dose periods, respectively. Following multiple doses of peficitinib, TEAEs were more frequent in higher than lower dose groups but were mild in severity with no related discontinuation or death.Conclusion: Following single and multiple doses of peficitinib in healthy Chinese subjects, peficitinib demonstrated rapid absorption and was well tolerated at all doses.Clinicaltrials.gov Identifier: NCT04143477.Keywords: rheumatoid arthritis, treatment, dose-proportionality, tsDMARDs

Published
2022

10. First demonstration of emulsion multi-stage shifter for accelerator neutrino experiment in J-PARC T60

Author

Yamada, K., Aoki, S., Cao, S., Chikuma, N., Fukuda, T., Fukuzawa, Y., Gonin, M., Hayashino, T., Hayato, Y., Hiramoto, A., Hosomi, F., Ishiguro, K., Iori, S., Inoh, T., Kawahara, H., Kim, H., Kitagawa, N., Koga, T., Komatani, R., Komatsu, M., Matsushita, A., Mikado, S., Minamino, A., Mizusawa, H., Morishima, K., Matsuo, T., Matsumoto, T., Morimoto, Y., Morishita, M., Nakamura, K., Nakamura, M., Nakamura, Y., Naganawa, N., Nakano, T., Nakaya, T., Nakatsuka, Y., Nishio, A., Ogawa, S., Oshima, H., Quilain, B., Rokujo, H., Sato, O., Seiya, Y., Shibuya, H., Shiraishi, T., Suzuki, Y., Tada, S., Takahashi, S., Yoshimoto, M., and Yokoyama, M.

Subjects
Physics - Instrumentation and Detectors
Abstract

We describe the first ever implementation of an emulsion multi-stage shifter in an accelerator neutrino experiment. The system was installed in the neutrino monitor building in J-PARC as a part of a test experiment T60 and stable operation was maintained for a total of 126.6 days. By applying time information to emulsion films, various results were obtained. Time resolutions of 5.3 to 14.7 s were evaluated in an operation spanning 46.9 days (time resolved numbers of 3.8--1.4$\times10^{5}$). By using timing and spatial information, a reconstruction of coincident events that consisted of high multiplicity events and vertex events, including neutrino events was performed. Emulsion events were matched to events observed by INGRID, one of near detectors of the T2K experiment, with high reliability (98.5\%) and hybrid analysis was established via use of the multi-stage shifter. The results demonstrate that the multi-stage shifter is feasible for use in neutrino experiments.

Published
2017

11. First neutrino event detection with nuclear emulsion at J-PARC neutrino beamline

Author

Fukuda, T., Aoki, S., Cao, S., Chikuma, N., Fukuzawa, Y., Gonin, M., Hayashino, T., Hayato, Y., Hiramoto, A., Hosomi, F., Ishiguro, K., Iori, S., Inoh, T., Kawahara, H., Kim, H., Kitagawa, N., Koga, T., Komatani, R., Komatsu, M., Matsushita, A., Mikado, S., Minamino, A., Mizusawa, H., Morishima, K., Matsuo, T., Matsumoto, T., Morimoto, Y., Morishita, M., Nakamura, K., Nakamura, M., Nakamura, Y., Naganawa, N., Nakano, T., Nakaya, T., Nakatsuka, Y., Nishio, A., Ogawa, S., Oshima, H., Quilain, B., Rokujo, H., Sato, O., Seiya, Y., Shibuya, H., Shiraishi, T., Suzuki, Y., Tada, S., Takahashi, S., Yamada, K., Yoshimoto, M., and Yokoyama, M.

Subjects
High Energy Physics - Experiment, Physics - Instrumentation and Detectors
Abstract

Precise neutrino--nucleus interaction measurements in the sub-multi GeV region are important to reduce the systematic uncertainty in future neutrino oscillation experiments. Furthermore, the excess of ${\nu_e}$ interactions, as a possible interpretation of the existence of a sterile neutrino has been observed in such an energy region. The nuclear emulsion technique can measure all the final state particles with low energy threshold for a variety of targets (Fe, C, H${_2}$O, and so on). Its sub-$\mu$m position resolution allows measurements of the ${\nu_e}$ cross-section with good electron/gamma separation capability. We started a new experiment at J-PARC to study sub-multi GeV neutrino interactions by introducing the nuclear emulsion technique. The J-PARC T60 experiment has been implemented as a first step of such a project. Systematic neutrino event analysis with full scanning data in the nuclear emulsion detector was performed for the first time. The first neutrino event detection and its analysis is described in this paper., Comment: 26 pages, 29 figures, 4 table, prepared for submission to PTEP

Published
2017
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12. Renal Recovery for Patients with ANCA-Associated Vasculitis and Low eGFR in the ADVOCATE Trial of Avacopan

Author

Cortazar, F. B., Niles, J. L., Jayne, D. R. W., Merkel, P. A., Bruchfeld, A., Yue, H., Schall, T. J., Bekker, P., Peh, C. A., Chakera, A., Cooper, B., Kurtkoti, J., Langguth, D., Levidiotis, V., Luxton, G., Mount, P., Mudge, D., Noble, E., Phoon, R., Ranganathan, D., Ritchie, A., Ryan, J., Suranyi, M., Rosenkranz, A., Lhotta, K., Kronbichler, A., Demoulin, N., Bovy, C., Hellemans, R., Hougardy, J., Sprangers, B., Wissing, K., Pagnoux, C., Barbour, S., Brachemi, S., Cournoyer, S., Girard, L., Laurin, L., Liang, P., Philibert, D., Walsh, M., Tesar, V., Becvar, R., Horak, P., Rychlik, I., Szpirt, W., Dieperink, H., Gregersen, J., Ivarsen, P., Krarup, E., Lyngsoe, C., Rigothier, C., Augusto, J., Belot, A., Chauveau, D., Cornec, D., Jourde-Chiche, N., Ficheux, M., Karras, A., Klein, A., Maurier, F., Mesbah, R., Moranne, O., Neel, A., Quemeneur, T., Saadoun, D., Terrier, B., Zaoui, P., Schaier, M., Benck, U., Bergner, R., Busch, M., Floege, J., Grundmann, F., Haller, H., Haubitz, M., Hellmich, B., Henes, J., Hohenstein, B., Hugo, C., Iking-Konert, C., Arndt, F., Kubacki, T., Kotter, I., Lamprecht, P., Lindner, T., Halbritter, J., Mehling, H., Schonermarck, U., Venhoff, N., Vielhauer, V., Witzke, O., Szombati, I., Szucs, G., Garibotto, G., Alberici, F., Brunetta, E., Dagna, L., De Vita, S., Emmi, G., Gabrielli, A., Manenti, L., Pieruzzi, F., Roccatello, D., Salvarani, C., Dobashi, H., Atsumi, T., Fujimoto, S., Hagino, N., Ihata, A., Kaname, S., Kaneko, Y., Katagiri, A., Katayama, M., Kirino, Y., Kitagawa, K., Komatsuda, A., Kono, H., Kurasawa, T., Matsumura, R., Mimura, T., Morinobu, A., Murakawa, Y., Naniwa, T., Nanki, T., Ogawa, N., Oshima, H., Sada, K., Sugiyama, E., Takeuchi, T., Taki, H., Tamura, N., Tsukamoto, T., Yamagata, K., Yamamura, M., van Daele, P., Rutgers, A., Teng, Y., Walker, R., Chua, I., Collins, M., Rabindranath, K., de Zoysa, J., Svensson, M., Grevbo, B., Kalstad, S., Little, M., Clarkson, M., Molloy, E., Pamplona, I. A., Anton, J., Lucia, V. B., Ciggaran, S., Cid, M. C., Encarnacion, M. D., Oliveras, X. F., Soler, M. J., Rusinol, H. M., Praga, M., Porras, L. Q., Segarra, A., Segelmark, M., Soveri, I., Thomaidi, E., Westman, K., Neumann, T., Burnier, M., Daikeler, T., Dudler, J., Hauser, T., Seeger, H., Vogt, B., Jayne, D., Burton, J., Al Jayyousi, R., Amin, T., Andrews, J., Baines, L., Brogan, P., Dasgupta, B., Doulton, T., Flossmann, O., Griffin, S., Harper, J., Harper, L., Kidder, D., Klocke, R., Lanyon, P., Luqmani, R., Mclaren, J., Makanjuola, D., Mccann, L., Nandagudi, A., Selvan, S., O'Riordan, E., Patel, M., Patel, R., Pusey, C., Rajakariar, R., Robson, J., Robson, M., Salama, A., Smyth, L., Sznajd, J., Taylor, J., Merkel, P., Sreih, A., Belilos, E., Bomback, A., Carlin, J., Chen Lin, Y. C., Derebail, V., Dragoi, S., Dua, A., Forbess, L., Geetha, D., Gipson, P., Gohh, R., Greenwood, G. T., Hugenberg, S., Jimenez, R., Kaskas, M., Kermani, T., Kivitz, A., Koening, C., Langford, C., Marder, G., Mohamed, A., Monach, P., Neyra, N., Niemer, G., Niles, J., Obi, R., Owens, C., Parks, D., Podoll, A., Rovin, B., Sam, R., Shergy, W., Silva, A., Specks, U., Spiera, R., Springer, J., Striebich, C., Swarup, A., Thakar, S., Tiliakos, A., Tsai, Y., Waguespack, D., Wasko, M. C., Cortazar, F, Niles, J, Jayne, D, Merkel, P, Bruchfeld, A, Yue, H, Schall, T, Bekker, P, Peh, C, Chakera, A, Cooper, B, Kurtkoti, J, Langguth, D, Levidiotis, V, Luxton, G, Mount, P, Mudge, D, Noble, E, Phoon, R, Ranganathan, D, Ritchie, A, Ryan, J, Suranyi, M, Rosenkranz, A, Lhotta, K, Kronbichler, A, Demoulin, N, Bovy, C, Hellemans, R, Hougardy, J, Sprangers, B, Wissing, K, Pagnoux, C, Barbour, S, Brachemi, S, Cournoyer, S, Girard, L, Laurin, L, Liang, P, Philibert, D, Walsh, M, Tesar, V, Becvar, R, Horak, P, Rychlik, I, Szpirt, W, Dieperink, H, Gregersen, J, Ivarsen, P, Krarup, E, Lyngsoe, C, Rigothier, C, Augusto, J, Belot, A, Chauveau, D, Cornec, D, Jourde-Chiche, N, Ficheux, M, Karras, A, Klein, A, Maurier, F, Mesbah, R, Moranne, O, Neel, A, Quemeneur, T, Saadoun, D, Terrier, B, Zaoui, P, Schaier, M, Benck, U, Bergner, R, Busch, M, Floege, J, Grundmann, F, Haller, H, Haubitz, M, Hellmich, B, Henes, J, Hohenstein, B, Hugo, C, Iking-Konert, C, Arndt, F, Kubacki, T, Kotter, I, Lamprecht, P, Lindner, T, Halbritter, J, Mehling, H, Schonermarck, U, Venhoff, N, Vielhauer, V, Witzke, O, Szombati, I, Szucs, G, Garibotto, G, Alberici, F, Brunetta, E, Dagna, L, De Vita, S, Emmi, G, Gabrielli, A, Manenti, L, Pieruzzi, F, Roccatello, D, Salvarani, C, Dobashi, H, Atsumi, T, Fujimoto, S, Hagino, N, Ihata, A, Kaname, S, Kaneko, Y, Katagiri, A, Katayama, M, Kirino, Y, Kitagawa, K, Komatsuda, A, Kono, H, Kurasawa, T, Matsumura, R, Mimura, T, Morinobu, A, Murakawa, Y, Naniwa, T, Nanki, T, Ogawa, N, Oshima, H, Sada, K, Sugiyama, E, Takeuchi, T, Taki, H, Tamura, N, Tsukamoto, T, Yamagata, K, Yamamura, M, van Daele, P, Rutgers, A, Teng, Y, Walker, R, Chua, I, Collins, M, Rabindranath, K, de Zoysa, J, Svensson, M, Grevbo, B, Kalstad, S, Little, M, Clarkson, M, Molloy, E, Pamplona, I, Anton, J, Lucia, V, Ciggaran, S, Cid, M, Encarnacion, M, Oliveras, X, Soler, M, Rusinol, H, Praga, M, Porras, L, Segarra, A, Segelmark, M, Soveri, I, Thomaidi, E, Westman, K, Neumann, T, Burnier, M, Daikeler, T, Dudler, J, Hauser, T, Seeger, H, Vogt, B, Burton, J, Al Jayyousi, R, Amin, T, Andrews, J, Baines, L, Brogan, P, Dasgupta, B, Doulton, T, Flossmann, O, Griffin, S, Harper, J, Harper, L, Kidder, D, Klocke, R, Lanyon, P, Luqmani, R, Mclaren, J, Makanjuola, D, Mccann, L, Nandagudi, A, Selvan, S, O'Riordan, E, Patel, M, Patel, R, Pusey, C, Rajakariar, R, Robson, J, Robson, M, Salama, A, Smyth, L, Sznajd, J, Taylor, J, Sreih, A, Belilos, E, Bomback, A, Carlin, J, Chen Lin, Y, Derebail, V, Dragoi, S, Dua, A, Forbess, L, Geetha, D, Gipson, P, Gohh, R, Greenwood, G, Hugenberg, S, Jimenez, R, Kaskas, M, Kermani, T, Kivitz, A, Koening, C, Langford, C, Marder, G, Mohamed, A, Monach, P, Neyra, N, Niemer, G, Obi, R, Owens, C, Parks, D, Podoll, A, Rovin, B, Sam, R, Shergy, W, Silva, A, Specks, U, Spiera, R, Springer, J, Striebich, C, Swarup, A, Thakar, S, Tiliakos, A, Tsai, Y, Waguespack, D, and Wasko, M

Subjects
avacopan, Clinical Research, renal recovery, Nephrology, low eGFR, complement 5a receptor, complement, ANCA-associated vasculiti
Abstract

INTRODUCTION: In the 330-patient ADVOCATE trial of avacopan for the treatment of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, in which 81% of patients had renal involvement, estimated glomerular filtration rate (eGFR) increased on average 7.3 ml/min per 1.73 m(2) in the avacopan group and 4.1 ml/min per 1.73 m(2) in the prednisone group (P = 0.029) at week 52. This new analysis examines the results in the patient subgroup with severe renal insufficiency at enrollment into the trial, i.e., eGFR ≤20 ml/min per 1.73 m(2). METHODS: eGFR was determined at baseline and over the course of the trial. Changes in eGFR were compared between the 2 treatment groups. RESULTS: In ADVOCATE, 27 of 166 patients (16%) in the avacopan group and 23 of 164 patients (14%) in the prednisone group had a baseline eGFR ≤20 ml/min per 1.73 m(2). At week 52, eGFR increased on average 16.1 and 7.7 ml/min per 1.73 m(2) in the avacopan and prednisone groups, respectively (P = 0.003). The last eGFR value measured during the 52-week treatment period was ≥2-fold higher than baseline in 41% of patients in the avacopan group compared to 13% in the prednisone group (P = 0.030). More patients in the avacopan group versus prednisone group had increases in eGFR above 20, 30, and 45 ml/min per 1.73 m(2), respectively. Serious adverse events occurred in 13 of 27 patients (48%) in the avacopan group and 16 of 23 patients (70%) in the prednisone group. CONCLUSION: Among patients with baseline eGFR ≤20 ml/min per 1.73 m(2) in the ADVOCATE trial, eGFR improved more in the avacopan group than in the prednisone group.

Published
2023

13. Renal Recovery for Patients with ANCA-Associated Vasculitis and Low eGFR in the ADVOCATE Trial of Avacopan

Author

Cortazar, F, Niles, J, Jayne, D, Merkel, P, Bruchfeld, A, Yue, H, Schall, T, Bekker, P, Peh, C, Chakera, A, Cooper, B, Kurtkoti, J, Langguth, D, Levidiotis, V, Luxton, G, Mount, P, Mudge, D, Noble, E, Phoon, R, Ranganathan, D, Ritchie, A, Ryan, J, Suranyi, M, Rosenkranz, A, Lhotta, K, Kronbichler, A, Demoulin, N, Bovy, C, Hellemans, R, Hougardy, J, Sprangers, B, Wissing, K, Pagnoux, C, Barbour, S, Brachemi, S, Cournoyer, S, Girard, L, Laurin, L, Liang, P, Philibert, D, Walsh, M, Tesar, V, Becvar, R, Horak, P, Rychlik, I, Szpirt, W, Dieperink, H, Gregersen, J, Ivarsen, P, Krarup, E, Lyngsoe, C, Rigothier, C, Augusto, J, Belot, A, Chauveau, D, Cornec, D, Jourde-Chiche, N, Ficheux, M, Karras, A, Klein, A, Maurier, F, Mesbah, R, Moranne, O, Neel, A, Quemeneur, T, Saadoun, D, Terrier, B, Zaoui, P, Schaier, M, Benck, U, Bergner, R, Busch, M, Floege, J, Grundmann, F, Haller, H, Haubitz, M, Hellmich, B, Henes, J, Hohenstein, B, Hugo, C, Iking-Konert, C, Arndt, F, Kubacki, T, Kotter, I, Lamprecht, P, Lindner, T, Halbritter, J, Mehling, H, Schonermarck, U, Venhoff, N, Vielhauer, V, Witzke, O, Szombati, I, Szucs, G, Garibotto, G, Alberici, F, Brunetta, E, Dagna, L, De Vita, S, Emmi, G, Gabrielli, A, Manenti, L, Pieruzzi, F, Roccatello, D, Salvarani, C, Dobashi, H, Atsumi, T, Fujimoto, S, Hagino, N, Ihata, A, Kaname, S, Kaneko, Y, Katagiri, A, Katayama, M, Kirino, Y, Kitagawa, K, Komatsuda, A, Kono, H, Kurasawa, T, Matsumura, R, Mimura, T, Morinobu, A, Murakawa, Y, Naniwa, T, Nanki, T, Ogawa, N, Oshima, H, Sada, K, Sugiyama, E, Takeuchi, T, Taki, H, Tamura, N, Tsukamoto, T, Yamagata, K, Yamamura, M, van Daele, P, Rutgers, A, Teng, Y, Walker, R, Chua, I, Collins, M, Rabindranath, K, de Zoysa, J, Svensson, M, Grevbo, B, Kalstad, S, Little, M, Clarkson, M, Molloy, E, Pamplona, I, Anton, J, Lucia, V, Ciggaran, S, Cid, M, Encarnacion, M, Oliveras, X, Soler, M, Rusinol, H, Praga, M, Porras, L, Segarra, A, Segelmark, M, Soveri, I, Thomaidi, E, Westman, K, Neumann, T, Burnier, M, Daikeler, T, Dudler, J, Hauser, T, Seeger, H, Vogt, B, Burton, J, Al Jayyousi, R, Amin, T, Andrews, J, Baines, L, Brogan, P, Dasgupta, B, Doulton, T, Flossmann, O, Griffin, S, Harper, J, Harper, L, Kidder, D, Klocke, R, Lanyon, P, Luqmani, R, Mclaren, J, Makanjuola, D, Mccann, L, Nandagudi, A, Selvan, S, O'Riordan, E, Patel, M, Patel, R, Pusey, C, Rajakariar, R, Robson, J, Robson, M, Salama, A, Smyth, L, Sznajd, J, Taylor, J, Sreih, A, Belilos, E, Bomback, A, Carlin, J, Chen Lin, Y, Derebail, V, Dragoi, S, Dua, A, Forbess, L, Geetha, D, Gipson, P, Gohh, R, Greenwood, G, Hugenberg, S, Jimenez, R, Kaskas, M, Kermani, T, Kivitz, A, Koening, C, Langford, C, Marder, G, Mohamed, A, Monach, P, Neyra, N, Niemer, G, Obi, R, Owens, C, Parks, D, Podoll, A, Rovin, B, Sam, R, Shergy, W, Silva, A, Specks, U, Spiera, R, Springer, J, Striebich, C, Swarup, A, Thakar, S, Tiliakos, A, Tsai, Y, Waguespack, D, Wasko, M, Cortazar F. B., Niles J. L., Jayne D. R. W., Merkel P. A., Bruchfeld A., Yue H., Schall T. J., Bekker P., Peh C. A., Chakera A., Cooper B., Kurtkoti J., Langguth D., Levidiotis V., Luxton G., Mount P., Mudge D., Noble E., Phoon R., Ranganathan D., Ritchie A., Ryan J., Suranyi M., Rosenkranz A., Lhotta K., Kronbichler A., Demoulin N., Bovy C., Hellemans R., Hougardy J., Sprangers B., Wissing K., Pagnoux C., Barbour S., Brachemi S., Cournoyer S., Girard L., Laurin L., Liang P., Philibert D., Walsh M., Tesar V., Becvar R., Horak P., Rychlik I., Szpirt W., Dieperink H., Gregersen J., Ivarsen P., Krarup E., Lyngsoe C., Rigothier C., Augusto J., Belot A., Chauveau D., Cornec D., Jourde-Chiche N., Ficheux M., Karras A., Klein A., Maurier F., Mesbah R., Moranne O., Neel A., Quemeneur T., Saadoun D., Terrier B., Zaoui P., Schaier M., Benck U., Bergner R., Busch M., Floege J., Grundmann F., Haller H., Haubitz M., Hellmich B., Henes J., Hohenstein B., Hugo C., Iking-Konert C., Arndt F., Kubacki T., Kotter I., Lamprecht P., Lindner T., Halbritter J., Mehling H., Schonermarck U., Venhoff N., Vielhauer V., Witzke O., Szombati I., Szucs G., Garibotto G., Alberici F., Brunetta E., Dagna L., De Vita S., Emmi G., Gabrielli A., Manenti L., Pieruzzi F., Roccatello D., Salvarani C., Dobashi H., Atsumi T., Fujimoto S., Hagino N., Ihata A., Kaname S., Kaneko Y., Katagiri A., Katayama M., Kirino Y., Kitagawa K., Komatsuda A., Kono H., Kurasawa T., Matsumura R., Mimura T., Morinobu A., Murakawa Y., Naniwa T., Nanki T., Ogawa N., Oshima H., Sada K., Sugiyama E., Takeuchi T., Taki H., Tamura N., Tsukamoto T., Yamagata K., Yamamura M., van Daele P., Rutgers A., Teng Y., Walker R., Chua I., Collins M., Rabindranath K., de Zoysa J., Svensson M., Grevbo B., Kalstad S., Little M., Clarkson M., Molloy E., Pamplona I. A., Anton J., Lucia V. B., Ciggaran S., Cid M. C., Encarnacion M. D., Oliveras X. F., Soler M. J., Rusinol H. M., Praga M., Porras L. Q., Segarra A., Segelmark M., Soveri I., Thomaidi E., Westman K., Neumann T., Burnier M., Daikeler T., Dudler J., Hauser T., Seeger H., Vogt B., Jayne D., Burton J., Al Jayyousi R., Amin T., Andrews J., Baines L., Brogan P., Dasgupta B., Doulton T., Flossmann O., Griffin S., Harper J., Harper L., Kidder D., Klocke R., Lanyon P., Luqmani R., McLaren J., Makanjuola D., McCann L., Nandagudi A., Selvan S., O'Riordan E., Patel M., Patel R., Pusey C., Rajakariar R., Robson J., Robson M., Salama A., Smyth L., Sznajd J., Taylor J., Merkel P., Sreih A., Belilos E., Bomback A., Carlin J., Chen Lin Y. C., Derebail V., Dragoi S., Dua A., Forbess L., Geetha D., Gipson P., Gohh R., Greenwood G. T., Hugenberg S., Jimenez R., Kaskas M., Kermani T., Kivitz A., Koening C., Langford C., Marder G., Mohamed A., Monach P., Neyra N., Niemer G., Niles J., Obi R., Owens C., Parks D., Podoll A., Rovin B., Sam R., Shergy W., Silva A., Specks U., Spiera R., Springer J., Striebich C., Swarup A., Thakar S., Tiliakos A., Tsai Y., Waguespack D., Wasko M. C., Cortazar, F, Niles, J, Jayne, D, Merkel, P, Bruchfeld, A, Yue, H, Schall, T, Bekker, P, Peh, C, Chakera, A, Cooper, B, Kurtkoti, J, Langguth, D, Levidiotis, V, Luxton, G, Mount, P, Mudge, D, Noble, E, Phoon, R, Ranganathan, D, Ritchie, A, Ryan, J, Suranyi, M, Rosenkranz, A, Lhotta, K, Kronbichler, A, Demoulin, N, Bovy, C, Hellemans, R, Hougardy, J, Sprangers, B, Wissing, K, Pagnoux, C, Barbour, S, Brachemi, S, Cournoyer, S, Girard, L, Laurin, L, Liang, P, Philibert, D, Walsh, M, Tesar, V, Becvar, R, Horak, P, Rychlik, I, Szpirt, W, Dieperink, H, Gregersen, J, Ivarsen, P, Krarup, E, Lyngsoe, C, Rigothier, C, Augusto, J, Belot, A, Chauveau, D, Cornec, D, Jourde-Chiche, N, Ficheux, M, Karras, A, Klein, A, Maurier, F, Mesbah, R, Moranne, O, Neel, A, Quemeneur, T, Saadoun, D, Terrier, B, Zaoui, P, Schaier, M, Benck, U, Bergner, R, Busch, M, Floege, J, Grundmann, F, Haller, H, Haubitz, M, Hellmich, B, Henes, J, Hohenstein, B, Hugo, C, Iking-Konert, C, Arndt, F, Kubacki, T, Kotter, I, Lamprecht, P, Lindner, T, Halbritter, J, Mehling, H, Schonermarck, U, Venhoff, N, Vielhauer, V, Witzke, O, Szombati, I, Szucs, G, Garibotto, G, Alberici, F, Brunetta, E, Dagna, L, De Vita, S, Emmi, G, Gabrielli, A, Manenti, L, Pieruzzi, F, Roccatello, D, Salvarani, C, Dobashi, H, Atsumi, T, Fujimoto, S, Hagino, N, Ihata, A, Kaname, S, Kaneko, Y, Katagiri, A, Katayama, M, Kirino, Y, Kitagawa, K, Komatsuda, A, Kono, H, Kurasawa, T, Matsumura, R, Mimura, T, Morinobu, A, Murakawa, Y, Naniwa, T, Nanki, T, Ogawa, N, Oshima, H, Sada, K, Sugiyama, E, Takeuchi, T, Taki, H, Tamura, N, Tsukamoto, T, Yamagata, K, Yamamura, M, van Daele, P, Rutgers, A, Teng, Y, Walker, R, Chua, I, Collins, M, Rabindranath, K, de Zoysa, J, Svensson, M, Grevbo, B, Kalstad, S, Little, M, Clarkson, M, Molloy, E, Pamplona, I, Anton, J, Lucia, V, Ciggaran, S, Cid, M, Encarnacion, M, Oliveras, X, Soler, M, Rusinol, H, Praga, M, Porras, L, Segarra, A, Segelmark, M, Soveri, I, Thomaidi, E, Westman, K, Neumann, T, Burnier, M, Daikeler, T, Dudler, J, Hauser, T, Seeger, H, Vogt, B, Burton, J, Al Jayyousi, R, Amin, T, Andrews, J, Baines, L, Brogan, P, Dasgupta, B, Doulton, T, Flossmann, O, Griffin, S, Harper, J, Harper, L, Kidder, D, Klocke, R, Lanyon, P, Luqmani, R, Mclaren, J, Makanjuola, D, Mccann, L, Nandagudi, A, Selvan, S, O'Riordan, E, Patel, M, Patel, R, Pusey, C, Rajakariar, R, Robson, J, Robson, M, Salama, A, Smyth, L, Sznajd, J, Taylor, J, Sreih, A, Belilos, E, Bomback, A, Carlin, J, Chen Lin, Y, Derebail, V, Dragoi, S, Dua, A, Forbess, L, Geetha, D, Gipson, P, Gohh, R, Greenwood, G, Hugenberg, S, Jimenez, R, Kaskas, M, Kermani, T, Kivitz, A, Koening, C, Langford, C, Marder, G, Mohamed, A, Monach, P, Neyra, N, Niemer, G, Obi, R, Owens, C, Parks, D, Podoll, A, Rovin, B, Sam, R, Shergy, W, Silva, A, Specks, U, Spiera, R, Springer, J, Striebich, C, Swarup, A, Thakar, S, Tiliakos, A, Tsai, Y, Waguespack, D, Wasko, M, Cortazar F. B., Niles J. L., Jayne D. R. W., Merkel P. A., Bruchfeld A., Yue H., Schall T. J., Bekker P., Peh C. A., Chakera A., Cooper B., Kurtkoti J., Langguth D., Levidiotis V., Luxton G., Mount P., Mudge D., Noble E., Phoon R., Ranganathan D., Ritchie A., Ryan J., Suranyi M., Rosenkranz A., Lhotta K., Kronbichler A., Demoulin N., Bovy C., Hellemans R., Hougardy J., Sprangers B., Wissing K., Pagnoux C., Barbour S., Brachemi S., Cournoyer S., Girard L., Laurin L., Liang P., Philibert D., Walsh M., Tesar V., Becvar R., Horak P., Rychlik I., Szpirt W., Dieperink H., Gregersen J., Ivarsen P., Krarup E., Lyngsoe C., Rigothier C., Augusto J., Belot A., Chauveau D., Cornec D., Jourde-Chiche N., Ficheux M., Karras A., Klein A., Maurier F., Mesbah R., Moranne O., Neel A., Quemeneur T., Saadoun D., Terrier B., Zaoui P., Schaier M., Benck U., Bergner R., Busch M., Floege J., Grundmann F., Haller H., Haubitz M., Hellmich B., Henes J., Hohenstein B., Hugo C., Iking-Konert C., Arndt F., Kubacki T., Kotter I., Lamprecht P., Lindner T., Halbritter J., Mehling H., Schonermarck U., Venhoff N., Vielhauer V., Witzke O., Szombati I., Szucs G., Garibotto G., Alberici F., Brunetta E., Dagna L., De Vita S., Emmi G., Gabrielli A., Manenti L., Pieruzzi F., Roccatello D., Salvarani C., Dobashi H., Atsumi T., Fujimoto S., Hagino N., Ihata A., Kaname S., Kaneko Y., Katagiri A., Katayama M., Kirino Y., Kitagawa K., Komatsuda A., Kono H., Kurasawa T., Matsumura R., Mimura T., Morinobu A., Murakawa Y., Naniwa T., Nanki T., Ogawa N., Oshima H., Sada K., Sugiyama E., Takeuchi T., Taki H., Tamura N., Tsukamoto T., Yamagata K., Yamamura M., van Daele P., Rutgers A., Teng Y., Walker R., Chua I., Collins M., Rabindranath K., de Zoysa J., Svensson M., Grevbo B., Kalstad S., Little M., Clarkson M., Molloy E., Pamplona I. A., Anton J., Lucia V. B., Ciggaran S., Cid M. C., Encarnacion M. D., Oliveras X. F., Soler M. J., Rusinol H. M., Praga M., Porras L. Q., Segarra A., Segelmark M., Soveri I., Thomaidi E., Westman K., Neumann T., Burnier M., Daikeler T., Dudler J., Hauser T., Seeger H., Vogt B., Jayne D., Burton J., Al Jayyousi R., Amin T., Andrews J., Baines L., Brogan P., Dasgupta B., Doulton T., Flossmann O., Griffin S., Harper J., Harper L., Kidder D., Klocke R., Lanyon P., Luqmani R., McLaren J., Makanjuola D., McCann L., Nandagudi A., Selvan S., O'Riordan E., Patel M., Patel R., Pusey C., Rajakariar R., Robson J., Robson M., Salama A., Smyth L., Sznajd J., Taylor J., Merkel P., Sreih A., Belilos E., Bomback A., Carlin J., Chen Lin Y. C., Derebail V., Dragoi S., Dua A., Forbess L., Geetha D., Gipson P., Gohh R., Greenwood G. T., Hugenberg S., Jimenez R., Kaskas M., Kermani T., Kivitz A., Koening C., Langford C., Marder G., Mohamed A., Monach P., Neyra N., Niemer G., Niles J., Obi R., Owens C., Parks D., Podoll A., Rovin B., Sam R., Shergy W., Silva A., Specks U., Spiera R., Springer J., Striebich C., Swarup A., Thakar S., Tiliakos A., Tsai Y., Waguespack D., and Wasko M. C.

Abstract

Introduction: In the 330-patient ADVOCATE trial of avacopan for the treatment of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, in which 81% of patients had renal involvement, estimated glomerular filtration rate (eGFR) increased on average 7.3 ml/min per 1.73 m2 in the avacopan group and 4.1 ml/min per 1.73 m2 in the prednisone group (P = 0.029) at week 52. This new analysis examines the results in the patient subgroup with severe renal insufficiency at enrollment into the trial, i.e., eGFR ≤20 ml/min per 1.73 m2. Methods: eGFR was determined at baseline and over the course of the trial. Changes in eGFR were compared between the 2 treatment groups. Results: In ADVOCATE, 27 of 166 patients (16%) in the avacopan group and 23 of 164 patients (14%) in the prednisone group had a baseline eGFR ≤20 ml/min per 1.73 m2. At week 52, eGFR increased on average 16.1 and 7.7 ml/min per 1.73 m2 in the avacopan and prednisone groups, respectively (P = 0.003). The last eGFR value measured during the 52-week treatment period was ≥2-fold higher than baseline in 41% of patients in the avacopan group compared to 13% in the prednisone group (P = 0.030). More patients in the avacopan group versus prednisone group had increases in eGFR above 20, 30, and 45 ml/min per 1.73 m2, respectively. Serious adverse events occurred in 13 of 27 patients (48%) in the avacopan group and 16 of 23 patients (70%) in the prednisone group. Conclusion: Among patients with baseline eGFR ≤20 ml/min per 1.73 m2 in the ADVOCATE trial, eGFR improved more in the avacopan group than in the prednisone group.

Published
2023

18. Measurements of protons and charged pions emitted from <math><msub><mi>ν</mi><mi>μ</mi></msub></math> charged-current interactions on iron at a mean neutrino energy of 1.49 GeV using a nuclear emulsion detector

Author

Oshima, H., Matsuo, T., Ali, A., Aoki, S., Berns, L., Fukuda, T., Hanaoka, Y., Hayato, Y., Hiramoto, A., Ichikawa, A. K., Inamoto, H., Kasumi, A., Kawahara, H., Kikawa, T., Komatani, R., Komatsu, M., Kuretsubo, K., Marushima, T., Matsumoto, H., Mikado, S., Minamino, A., Mizuno, K., Morimoto, Y., Morishima, K., Naganawa, N., Naiki, M., Nakamura, M., Nakamura, Y., Nakano, T., Nakaya, T., Nishio, A., Odagawa, T., Ogawa, S., Rokujo, H., Sato, O., Shibuya, H., Sugimura, K., Suzui, L., Suzuki, Y., Takagi, H., Takahashi, S., Takao, T., Tanihara, Y., Watanabe, M., Yamada, K., Yasutome, K., Yokoyama, M., and Yoshimoto, M.

Abstract

This study conducted an analysis of muons, protons, and charged pions emitted from νμ charged-current interactions on iron using a nuclear emulsion detector. The emulsion detector with a 65 kg iron target was exposed to a neutrino beam corresponding to 4.0×1019 protons on target with a mean neutrino energy of 1.49 GeV. The measurements were performed at a momentum threshold of 200 (50) MeV/c for protons (pions), which are the lowest momentum thresholds attempted up to now. The measured quantities are the multiplicities, emission angles, and momenta of the muons, protons, and charged pions. In addition to these inclusive measurements, exclusive measurements such as the muon-proton emission-angle correlations of specific channels and the opening angle between the protons of CC0π2p events were performed. The data were compared to Monte Carlo predictions and some significant differences were observed. The results of the study demonstrate the capability of detailed measurements of neutrino-nucleus interactions using a nuclear emulsion detector to improve neutrino interaction models.

Published
2022

31. Intracellular localization of AMP deaminase and its novel role in BCAA and lipid metabolism in diabetic cardiomyopathy

Author

Ogawa, T, primary, Kouzu, H, additional, Osanami, A, additional, Tatekoshi, Y, additional, Oshima, H, additional, Mizuno, M, additional, Kuno, A, additional, Fujita, Y, additional, Ino, S, additional, Shimizu, M, additional, Ohwada, W, additional, Sato, T, additional, Yano, T, additional, Tanno, M, additional, and Miura, T, additional

Published
2021
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35. Avacopan for the Treatment of ANCA-Associated Vasculitis

Author

Jayne, David R W, Merkel, Peter A, Schall, Thomas J, Bekker, Pirow, ADVOCATE Study Group:, C Au Peh, Chakera, A, Cooper, B, Kurtkoti, J, Langguth, D, Levidiotis, V, Luxton, G, Mount, P, Mudge, D, Noble, E, Phoon, R, Ranganathan, D, Ritchie, A, Ryan, J, Suranyi, M, Rosenkranz, A, Lhotta, K, Kronbichler, A, Demoulin, N, Bovy, C, Hellemans, R, Hougardy, J, Sprangers, B, Wissing, K, Pagnoux, C, Barbour, S, Brachemi, S, Cournoyer, S, Girard, L, Laurin, L, Liang, P, Philibert, D, Walsh, M, Tesar, V, Becvar, R, Horak, P, Rychlik, I, Szpirt, W, Dieperink, H, Gregersen, J, Ivarsen, P, Krarup, E, Lyngsoe, C, Rigothier, C, Augusto, J, Belot, A, Chauveau, D, Cornec, D, Jourde-Chiche, N, Ficheux, M, Karras, A, Klein, A, Maurier, F, Mesbah, R, Moranne, O, Neel, A, Quemeneur, T, Saadoun, D, Terrier, B, Zaoui, P, Schaier, M, Benck, U, Bergner, R, Busch, M, Floege, J, Grundmann, F, Haller, H, Haubitz, M, Hellmich, B, Henes, J, Hohenstein, B, Hugo, C, Iking-Konert, C, Arndt, F, Kubacki, T, Kotter, I, Lamprecht, P, Lindner, T, Halbritter, J, Mehling, H, Schönermarck, U, Venhoff, N, Vielhauer, V, Witzke, O, Szombati, I, Szucs, G, Garibotto, G, Alberici, F, Brunetta, E, Dagna, L, S De Vita, Emmi, G, Gabrielli, A, Manenti, L, Pieruzzi, F, Roccatello, D, Salvarani, C, Dobashi, H, Atsumi, T, Fujimoto, S, Hagino, N, Ihata, A, Kaname, S, Kaneko, Y, Katagiri, A, Katayama, M, Kirino, Y, Kitagawa, K, Komatsuda, A, Kono, H, Kurasawa, T, Matsumura, R, Mimura, T, Morinobu, A, Murakawa, Y, Naniwa, T, Nanki, T, Ogawa, N, Oshima, H, Sada, K, Sugiyama, E, Takeuchi, T, Taki, H, Tamura, N, Tsukamoto, T, Yamagata, K, Yamamura, M, P van Daele, Rutgers, A, Teng, Y, Walker, R, Chua, I, Collins, M, Rabindranath, K, J de Zoysa, Svensson, M, Grevbo, B, Kalstad, S, Little, M, Clarkson, M, Molloy, E, I Agraz Pamplona, Anton, J, V Barrio Lucia, Ciggaran, S, M Cinta Cid, M Diaz Encarnacion, X Fulladosa Oliveras, M Soler, J, H Rusinol, M, Praga, M, L Quintana Porras, Segarra, A, Bruchfeld, A, Segelmark, M, Soveri, I, Thomaidi, E, Westman, K, Neumann, T, Burnier, M, Daikeler, T, Dudler, J, Hauser, T, Seeger, H, Vogt, B, Jayne, D, Burton, J, R Al Jayyousi, Amin, T, Andrews, J, Baines, L, Brogan, P, Dasgupta, B, Doulton, T, Flossmann, O, Griffin, S, Harper, J, Harper, L, Kidder, D, Klocke, R, Lanyon, P, Luqmani, R, Mclaren, J, Makanjuola, D, Mccann, L, Nandagudi, A, Selvan, S, O'Riordan, E, Patel, M, Patel, R, Pusey, C, Rajakariar, R, Robson, J, Robson, M, Salama, A, Smyth, L, Sznajd, J, Taylor, J, Merkel, P, Sreih, A, Belilos, E, Bomback, A, Carlin, J, Y Chang Chen Lin, Derebail, V, Dragoi, S, Dua, A, Forbess, L, Geetha, D, Gipson, P, Gohh, R, T Greenwood, G, Hugenberg, S, Jimenez, R, Kaskas, M, Kermani, T, Kivitz, A, Koening, C, Langford, C, Marder, G, Mohamed, A, Monach, P, Neyra, N, Niemer, G, Niles, J, Obi, R, Owens, C, Parks, D, Podoll, A, Rovin, B, Sam, R, Shergy, W, Silva, A, Specks, U, Spiera, R, Springer, J, Striebich, C, Swarup, A, Thakar, S, Tiliakos, A, Tsai, Y, Waguespack, D, M Chester Wasko, Internal Medicine, Immunology, Jayne, D, Merkel, P, Schall, T, Bekker, P, Pieruzzi, F, Jayne, David RW [0000-0002-1712-0637], Apollo - University of Cambridge Repository, and Translational Immunology Groningen (TRIGR)

Subjects
Male, Receptor, Anaphylatoxin C5a/antagonists & inhibitors, Anaphylatoxin C5a, Anaphylatoxin C5a/antagonists & inhibitors, Nipecotic Acids, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculiti, Administration, Oral, Azathioprine, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, urologic and male genital diseases, Gastroenterology, C5a receptor, Cyclophosphamide/administration & dosage, Rituximab/administration & dosage, Immunosuppressive Agent, renal vasculitis, Prednisone/administration & dosage, 0302 clinical medicine, Glucocorticoid, immune system diseases, Prednisone, Recurrence, Medicine, 030212 general & internal medicine, skin and connective tissue diseases, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy, Aniline Compounds, Remission Induction, General Medicine, Aniline Compound, Middle Aged, Administration, Combination, Rituximab, Drug Therapy, Combination, Female, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Cyclophosphamide, Double-Blind Method, Glucocorticoids, Humans, Immunosuppressive Agents, Receptor, Anaphylatoxin C5a, Vasculitis, Receptor, medicine.drug, Human, Azathioprine/administration & dosage, Oral, medicine.medical_specialty, Nipecotic Acid, ANCA-Associated Vasculitis, 03 medical and health sciences, Drug Therapy, Internal medicine, Aniline Compounds/adverse effects, cardiovascular diseases, Immunosuppressive Agents/administration & dosage, Anti-neutrophil cytoplasmic antibody, business.industry, Glucocorticoids/administration & dosage, medicine.disease, Nipecotic Acids/adverse effects, respiratory tract diseases, business
Abstract

BACKGROUND: The C5a receptor inhibitor avacopan is being studied for the treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis.METHODS: In this randomized, controlled trial, we assigned patients with ANCA-associated vasculitis in a 1:1 ratio to receive oral avacopan at a dose of 30 mg twice daily or oral prednisone on a tapering schedule. All the patients received either cyclophosphamide (followed by azathioprine) or rituximab. The first primary end point was remission, defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 (on a scale from 0 to 63, with higher scores indicating greater disease activity) at week 26 and no glucocorticoid use in the previous 4 weeks. The second primary end point was sustained remission, defined as remission at both weeks 26 and 52. Both end points were tested for noninferiority (by a margin of 20 percentage points) and for superiority.RESULTS: A total of 331 patients underwent randomization; 166 were assigned to receive avacopan, and 165 were assigned to receive prednisone. The mean BVAS at baseline was 16 in both groups. Remission at week 26 (the first primary end point) was observed in 120 of 166 patients (72.3%) receiving avacopan and in 115 of 164 patients (70.1%) receiving prednisone (estimated common difference, 3.4 percentage points; 95% confidence interval [CI], -6.0 to 12.8; PCONCLUSIONS: In this trial involving patients with ANCA-associated vasculitis, avacopan was noninferior but not superior to prednisone taper with respect to remission at week 26 and was superior to prednisone taper with respect to sustained remission at week 52. All the patients received cyclophosphamide or rituximab. The safety and clinical effects of avacopan beyond 52 weeks were not addressed in the trial. (Funded by ChemoCentryx; ADVOCATE ClinicalTrials.gov number, NCT02994927.).

Published
2021

36. STAT3-mediated upregulation of the AIM2 DNA sensor links innate immunity with cell migration to promote epithelial tumourigenesis.

Author

Dawson R.E., Deswaerte V., West A.C., Tang K., West A.J., Balic J.J., Gearing L.J., Saad M.I., Yu L., Wu Y., Bhathal P.S., Kumar B., Chakrabarti J.T., Zavros Y., Oshima H., Klinman D.M., Oshima M., Tan P., Jenkins B.J., Dawson R.E., Deswaerte V., West A.C., Tang K., West A.J., Balic J.J., Gearing L.J., Saad M.I., Yu L., Wu Y., Bhathal P.S., Kumar B., Chakrabarti J.T., Zavros Y., Oshima H., Klinman D.M., Oshima M., Tan P., and Jenkins B.J.

Abstract

OBJECTIVE: The absent in melanoma 2 (AIM2) cytosolic pattern recognition receptor and DNA sensor promotes the pathogenesis of autoimmune and chronic inflammatory diseases via caspase-1-containing inflammasome complexes. However, the role of AIM2 in cancer is ill-defined. DESIGN: The expression of AIM2 and its clinical significance was assessed in human gastric cancer (GC) patient cohorts. Genetic or therapeutic manipulation of AIM2 expression and activity was performed in the genetically engineered gp130F/F spontaneous GC mouse model, as well as human GC cell line xenografts. The biological role and mechanism of action of AIM2 in gastric tumourigenesis, including its involvement in inflammasome activity and functional interaction with microtubule-associated end-binding protein 1 (EB1), was determined in vitro and in vivo. RESULT(S): AIM2 expression is upregulated by interleukin-11 cytokine-mediated activation of the oncogenic latent transcription factor STAT3 in the tumour epithelium of GC mouse models and patients with GC. Genetic and therapeutic targeting of AIM2 in gp130F/F mice suppressed tumourigenesis. Conversely, AIM2 overexpression augmented the tumour load of human GC cell line xenografts. The protumourigenic function of AIM2 was independent of inflammasome activity and inflammation. Rather, in vivo and in vitro AIM2 physically interacted with EB1 to promote epithelial cell migration and tumourigenesis. Furthermore, upregulated expression of AIM2 and EB1 in the tumour epithelium of patients with GC was independently associated with poor patient survival. CONCLUSION(S): AIM2 can play a driver role in epithelial carcinogenesis by linking cytokine-STAT3 signalling, innate immunity and epithelial cell migration, independent of inflammasome activation.Copyright © Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Published
2021

37. Double‐probe measurement in recombining plasma using NAGDIS‐II

Author

Hayashi, Yuki, Nishikata, H., OHNO, Noriyasu, KAJITA, Shin, TANAKA, Hirohiko, Oshima, H., Seki, >, Hayashi, Yuki, Nishikata, H., OHNO, Noriyasu, KAJITA, Shin, TANAKA, Hirohiko, Oshima, H., and Seki, >

Abstract

We have studied the validity of the double-probe method in recombining plasmas. Electron temperature (Te) measured with a double probe was quantitatively evaluated by taking into account the influences of plasma potential fluctuation, plasma resistivity, and electron density fluctuation on the current–voltage characteristics. Differential potential fluctuation and plasma resistivity between two electrodes have a minor effect on Te especially when the inter-distance is small (typically 1 mm). Scattering of measured Te due to the density fluctuation was sufficiently suppressed by making the data acquisition time long (typically 4 s) and taking the average. There is a good agreement between Te measured with the optimized double-probe method and that with laser Thomson scattering diagnostics., source:https://doi.org/10.1002/ctpp.201800088, identifier:0000-0001-6090-5010

Published
2021

45. AB0145 SMARTPHONE- AND SMARTWATCH-ACQUIRED DAILY STEPS, ACTIVITY, AND BAROMETRIC PRESSURES ASSOCIATED WITH SUBJECTIVE MEASURES OF RHEUMATOID ARTHRITIS: A PROSPECTIVE STUDY FOR RA DIGITAL PHENOTYPING

Author

Izumi, K., primary, Moriwaki, D., additional, Toda, T., additional, Higashida-Konishi, M., additional, Koyama, M., additional, Oshima, H., additional, Okano, Y., additional, Kaneko, Y., additional, Ko, S., additional, and Takeuchi, T., additional

Published
2021
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46. First measurement using a nuclear emulsion detector of theνμcharged-current cross section on iron around the 1 GeV energy region

Author

Oshima, H, primary, Matsuo, T, additional, Ali, A, additional, Aoki, S, additional, Berns, L, additional, Fukuda, T, additional, Hanaoka, Y, additional, Hayato, Y, additional, Hiramoto, A, additional, Ichikawa, A K, additional, Kawahara, H, additional, Kikawa, T, additional, Komatani, R, additional, Komatsu, M, additional, Kuretsubo, K, additional, Marushima, T, additional, Matsumoto, H, additional, Mikado, S, additional, Minamino, A, additional, Mizuno, K, additional, Morimoto, Y, additional, Morishima, K, additional, Naganawa, N, additional, Naiki, M, additional, Nakamura, M, additional, Nakamura, Y, additional, Nakano, N, additional, Nakano, T, additional, Nakaya, T, additional, Nishio, A, additional, Odagawa, T, additional, Ogawa, S, additional, Rokujo, H, additional, Sato, O, additional, Shibuya, H, additional, Sugimura, K, additional, Suzui, L, additional, Suzuki, Y, additional, Takagi, H, additional, Takahashi, S, additional, Takao, T, additional, Tanihara, Y, additional, Watanabe, R, additional, Yamada, K, additional, Yasutome, K, additional, and Yokoyama, M, additional

Published
2021
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47. First measurement of <math><msub><mover><mi>ν</mi><mo>¯</mo></mover><mi>μ</mi></msub></math> and <math><msub><mi>ν</mi><mi>μ</mi></msub></math> charged-current inclusive interactions on water using a nuclear emulsion detector

Author

Hiramoto, A., Suzuki, Y., Ali, A., Aoki, Shigeki, Berns, L., Fukuda, T., Hanaoka, Y., Hayato, Y., Ichikawa, A. K., Kawahara, H., Kikawa, T., Koga, T., Komatani, R., Komatsu, M., Kosakai, Y., Matsuo, T., Mikado, S., Minamino, A., Mizuno, K., Morimoto, Y., Morishima, K., Naganawa, N., Naiki, M., Nakamura, M., Nakamura, Y., Nakano, N., Nakano, T., Nakaya, T., Nishio, A., Odagawa, T., Ogawa, S., Oshima, H., Rokujo, H., Sanjana, I., Sato, O., Shibuya, H., Sugimura, K., Suzui, L., Takagi, H., Takao, T., Tanihara, Y., Yasutome, K., and Yokoyama, M.

Subjects
Physics::Instrumentation and Detectors, Nuclear Theory, High Energy Physics::Experiment, Nuclear Experiment
Abstract

This paper reports the track multiplicity and kinematics of muons, charged pions, and protons from charged-current inclusive ν¯μ and νμ interactions on a water target, measured using a nuclear emulsion detector in the NINJA experiment. A 3-kg water target was exposed to the T2K antineutrino-enhanced beam corresponding to 7.1×1020 protons on target with a mean energy of 1.3 GeV. Owing to the high granularity of the nuclear emulsion, protons with momenta down to 200 MeV/c from the neutrino-water interactions were detected. We find good agreement between the observed data and model predictions for all kinematic distributions other than the number of charged pions and the muon kinematics shapes. These results demonstrate the capability of measurements with nuclear emulsion to improve neutrino interaction models.

Published
2020

48. First measurement of ν¯μ and νμ charged-current inclusive interactions on water using a nuclear emulsion detector

Author

Hiramoto, A., Suzuki, Y., Ali, A., Aoki, S., Berns, L., Fukuda, T., Hanaoka, Y., Hayato, Y., Ichikawa, A. K., Kawahara, H., Kikawa, T., Koga, T., Komatani, R., Komatsu, M., Kosakai, Y., Matsuo, T., Mikado, S., Minamino, A., Mizuno, K., Morimoto, Y., Morishima, K., Naganawa, N., Naiki, M., Nakamura, M., Nakamura, Y., Nakano, N., Nakano, T., Nakaya, T., Nishio, A., Odagawa, T., Ogawa, S., Oshima, H., Rokujo, H., Sanjana, I., Sato, O., Shibuya, H., Sugimura, K., Suzui, L., Takagi, H., Takao, T., Tanihara, Y., Yasutome, K., Yokoyama, M., and NINJA Collaboration

Subjects
Physics::Instrumentation and Detectors, Nuclear Theory, High Energy Physics::Experiment, Nuclear Experiment
Abstract

This paper reports the track multiplicity and kinematics of muons, charged pions, and protons from charged-current inclusive ¯νμ and νμ interactions on a water target, measured using a nuclear emulsion detector in the NINJA experiment. A 3-kg water target was exposed to the T2K antineutrino-enhanced beam corresponding to 7.1×1020 protons on target with a mean energy of 1.3 GeV. Owing to the high granularity of the nuclear emulsion, protons with momenta down to 200 MeV/c from the neutrino-water interactions were detected. We find good agreement between the observed data and model predictions for all kinematic distributions other than the number of charged pions and the muon kinematics shapes. These results demonstrate the capability of measurements with nuclear emulsion to improve neutrino interaction models., 精密測定により素粒子ニュートリノの謎の解明を目指すNINJA実験の物理解析が開始. 京都大学プレスリリース. 2020-10-21.

Published
2020

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Author

Hiramoto, A., Suzuki, Y., Ali, A., Aoki, S., Berns, L., Fukuda, T., Hanaoka, Y., Hayato, Y., Ichikawa, A. K., Kawahara, H., Kikawa, T., Koga, T., Komatani, R., Komatsu, M., Kosakai, Y., Matsuo, T., Mikado, S., Minamino, A., Mizuno, K., Morimoto, Y., Morishima, K., Naganawa, N., Naiki, M., Nakamura, M., Nakamura, Y., Nakano, N., Nakano, T., Nakaya, T., Nishio, A., Odagawa, T., Ogawa, S., Oshima, H., Rokujo, H., Sanjana, I., Sato, O., Shibuya, H., Sugimura, K., Suzui, L., Takagi, H., Takao, T., Tanihara, Y., Yasutome, K., Yokoyama, M., NINJA Collaboration, Hiramoto, A., Suzuki, Y., Ali, A., Aoki, S., Berns, L., Fukuda, T., Hanaoka, Y., Hayato, Y., Ichikawa, A. K., Kawahara, H., Kikawa, T., Koga, T., Komatani, R., Komatsu, M., Kosakai, Y., Matsuo, T., Mikado, S., Minamino, A., Mizuno, K., Morimoto, Y., Morishima, K., Naganawa, N., Naiki, M., Nakamura, M., Nakamura, Y., Nakano, N., Nakano, T., Nakaya, T., Nishio, A., Odagawa, T., Ogawa, S., Oshima, H., Rokujo, H., Sanjana, I., Sato, O., Shibuya, H., Sugimura, K., Suzui, L., Takagi, H., Takao, T., Tanihara, Y., Yasutome, K., Yokoyama, M., and NINJA Collaboration

Published
2020

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