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5. Pseudoirreversible inhibition elicits persistent efficacy of a sphingosine 1-phosphate receptor 1 antagonist

Author

Yuya Maruyama, Yusuke Ohsawa, Takayuki Suzuki, Yuko Yamauchi, Kohsuke Ohno, Hitoshi Inoue, Akitoshi Yamamoto, Morimichi Hayashi, Yuji Okuhara, Wataru Muramatsu, Kano Namiki, Naho Hagiwara, Maki Miyauchi, Takahisa Miyao, Tatsuya Ishikawa, Kenta Horie, Mio Hayama, Nobuko Akiyama, Takatsugu Hirokawa, and Taishin Akiyama

Subjects
Science
Abstract

Abstract Sphingosine 1-phosphate receptor 1 (S1PR1), a G protein-coupled receptor, is required for lymphocyte trafficking, and is a promising therapeutic target in inflammatory diseases. Here, we synthesize a competitive S1PR1 antagonist, KSI-6666, that effectively suppresses pathogenic inflammation. Metadynamics simulations suggest that the interaction of KSI-6666 with a methionine residue Met124 in the ligand-binding pocket of S1PR1 may inhibit the dissociation of KSI-6666 from S1PR1. Consistently, in vitro functional and mutational analyses reveal that KSI-6666 causes pseudoirreversible inhibition of S1PR1, dependent on the Met124 of the protein and substituents on the distal benzene ring of KSI-6666. Moreover, in vivo study suggests that this pseudoirreversible inhibition is responsible for the persistent activity of KSI-6666.

Published
2024
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12. 93rd annual convention podium and poster abstracts

Author

Davis, C. M., Strong, S. A., Hellinger, M. D., Williamson, P. R., Larach, S. W., Ferrara, A., Blake, T. B., Medich, D. S., Ziv, Y., Oakley, J. R., Reissman, P., Piccirillo, M., Ulrich, A., Nogueras, J. J., Wexner, S. D., Rubin, M. S., Bodenstein, L. E., Kent, K. C., Williamson, M. E. R., Lewis, W. G., Sagar, P. M., Holdsworth, P. J., Johnston, D., Fazio, V. W., Goldblum, J. R., Sirimarco, M. T., Lavery, I. C., Petras, R. E., Treem, W. R., Cohen, J., Davis, P. M., Hyams, J. S., Eu, K. W., Bartolo, D. C. C., Green, J. D., Riether, R. D., Rosen, L., Stasik, J. J., Sheets, J. A., Reed, J., Khubchandani, I. T., Armitage, N. C., Chapman, M., Hardcastle, J. D., Viamonte, M., Plasencia, G., Wiltz, O., Jacobs, M., Finan, P. J., Passaro, M., Church, J. M., McGannon, E., Wilson, M., Hull-Boiner, S., Kollmorgen, C. F., Meagher, A. P., Wolff, B. G., Pemberton, J. H., Martenson, J. A., Ilstrup, D. M., Moran, M. R., Ramos, A., Rothenberger, D. A., Goldberg, S. M., Johnson, D., Madoff, R. D., Wong, W. D., Finne, III, C. O., Konishi, F., Furuta, K., Kanazawa, K., Lockhart, D., Schmitt, S., Caushaj, P. P., Garcia-Aguilar, J., Belmonte, C., Schiesel, E. C., Mazier, W. P., Senagore, A. J., Piccirillo, M. F., Teoh, T. -A., Yoon, K. -S., Paul, R. A. Patino, Lucas, J., Nelson, R., Norton, N., Cautley, E., Schouten, W. R., Briel, J. W., Auwerda, J. J. A., de Graaf, E. J. R., Lowry, A. C., Sentovich, S. M., Blatchford, G. J., Rivela, L. J., Thorson, A. G., Christensen, M. A., Jorge, J. M. N., Yang, Y. K., Shafik, A., Allendorf, J. D. F., Kayton, M. L., Libutti, S. K., Trokel, M. J., Whelan, R. L., Treat, M. R., Nowygrod, R., Bessler, M., Frank, R. E., Saclarides, T. J., Leurgans, S., Speziale, N. J., Drab, E., Rubin, D., Hull, T. L., Schroeder, T. K., Scholefield, J. H., Ogunbiyi, O. A., Smith, J. H. F., Rogers, K., Sharp, F., Longo, W. E., Vernava, III, A. M., Wade, T. P., Coplin, M. A., Virgo, K. S., Johnson, F. E., Brady, M., Kavolius, J., Quan, S. H. Q., Goldstein, E. T., Feldman, S., Shub, H. A., Bennett, D. R., Kumar, R., McMillen, M. A., Thornton, S., Khoury, D. A., Opelka, F. G., Teoh, T -A., Cohen, S. M., Weiss, E. G., Ortiz, H., De Miguel, M., Armendáriz, P., Rodriguez, J., Chocarro, C., Farouk, R., Dorrance, H. R., Duthie, G. S., Rainey, J. B., Morgado, Jr., P. J., Corman, M. L., Kawamura, Y. J., Sawada, T., Muto, T., Nagai, H., Hill, J., MacLennan, I., Binderow, S. R., Daniel, N., Ehrenpreis, E. D., Jensen, J. E., Bonner, G. F., Ruderman, W. B., Milsom, J. W., Gibbs, D. H., Beck, D. E., Hicks, T. C., Timmcke, A. E., Gathright, Jr, J. B., Cheong, D., Lucas, F. V., McGinity, M., Taylor, B. A., Godwin, P., Holdsworth, P., Lewis, W., Quirke, P., Williamson, M., Kokoszka, J., Pavel, D., Abcarian, H., Stephenson, B. M., Morgan, A. R., Salaman, J. R., Wheeler, M. H., Tran, T. C. K., Willemsen, W., Kuijpers, H. C., Lehman, J. F., Wiseman, J. S., MacFie, J., Sedman, P., May, J., Mancey-Jones, B., Johnstone, D., Nwariaku, F. E., Rochon, R. B., Huber, P. J., Carrico, C. J., Ortega, A., Beart, R., Winchester, D., Steele, G., Green, R., Caushaj, P. F., Devereaux, D., Griffey, S., Reiver, D., Kmiot, W. A., Baker, R., Luchtefeld, M. A., Anthone, G., Schlinkert, R., Roig, J. V., Villoslada, C., Solana, A., Alos, R., Hinojosa, J., Lledo, S., Johnson, D. R. E., Buie, W. D., Jensen, L. L., Heine, J., Hoffmann, B., Timmcke, A., Hicks, T., Opelka, F., Beck, D., Sousa, Jr., A., AraÚjo, S. A., Damico, F. M., Cordeiro, A. C., Pinotti, H. W., Gama, A. H., Fengler, S., Pearl, R., Orsay, C., Seow-Choen, F., Ho, J. M. S., Wiltz, O. H., Torregrosa, M., Brasch, R. C., Bufo, A. J., Krienberg, P., Johnson, G. P., Gowen, G. F., Mullen, P. D., Behrens, D., Hughes, T. G., Wynn, M., Pollack, J. S., Rajagopal, A. S., Huynh, T., Schanbacher, C., Hickson, W. G. E., Yang, Y. -K., Heymen, S., Choi, S. -K., Teoh, T. -A., Wexner, S. D., Vaccaro, C. A., Teoh, T. A., Nogueras, J. J., Choi, S. K., Cheong, D. M. O., Salanga, V. D., MacDonald, A., Baxter, J. N., Finlay, I. G., Mellgren, A., Bremmer, S., Dolk, A., Gillgren, P., Johansson, C., Ahlbäck, S. O., Udén, R., Holmström, B., Ferrara, A., O'Donovan, S., Larach, S. W., Williamson, P. R., Neto, J. A. Reis, Ciquini, S., Quilici, F. A., Reis, Jr., J. A., Torrabadella, L., Salgado, G., Whelan, R. L., Horvath, K. D., Golub, R., Ahsan, H., Cirocco, W., Ziv, Y., Fazio, V. W., Oakley, J. R., Church, J. M., Milsom, J. W., Lavery, L. C., Cohen, S. M., Kmiot, W. A., Reiver, D., Reissman, P., Weiss, E. G., Alós, R., García-Granero, E., Roig, J. V., Uribe, N., Sala, C., Lledo, S., Ozuner, G., Strong, S. A., Bufo, A. J., Daniels, G., Lieberman, R. C., Feldman, S., Lucas, F. V., Longo, W. E., Polites, G., Deshpande, Y., Vernava, A. M., Niehoff, M., Chandel, B., Berglund, D. D., Madoff, R. D., Gemlo, B. T., Spencer, M. P., Goldberg, S. M., Lowry, A. C., Marcello, P. W., Roberts, P. L., Schoetz, D. J., Murray, J. J., Coller, J. A., Veidenheimer, M. C., Koltun, W. A., Bloomer, M. M., Colony, P., Ruggeiro, F., Fleshner, P. R., Michelassi, F., Lewis, W., Williamson, M., Holdsworth, P., Finan, P., Ash, D., Johnston, D., Moran, M. R., Ramos, A., Rothenberger, D. A., Antonenko, D. R., Khanduja, K. S., Fitzgerald, S. D., Meagher, A. P., Moniz-Pereira, P., Wolff, B. G., Outwater, E. K., Marks, G. J., Mohiuddin, M., Sagar, P. M., Hartley, M. N., Mancey-Jones, B., Sedman, P., May, J., MacFie, J., Holbrook, R. F., Rodriguez-Bigas, M. A., Ramakrishnan, K., Palmer, M. L., Petrelli, N. J., Takahashi, T., Nivatvongs, S., Batts, K. P., Lucas, S. W., Klein, S. N., Keidan, R. D., Bannon, J. P., Zhou, J., Armitage, N. C., Hunt, L. M., Robinson, M. H., Hugkulstone, C. E., Clarke, B., Vernon, S. A., Gregson, R. H., Hardcastle, J. D., Ryan, M., Dutta, S., Levine, A., Ortega, A., Anthone, G., Beart, R., Dominguez, J. M., Saclarides, T. J., Bolan, P., Bines, S. D., Adachi, M., Watanabe, T., Sawada, T., Okinaga, K., Muto, T., Hase, K., Shatney, C., Mochizuki, H., Johnson, D., Ure, T., Dehghan, K., Andrus, C. A., Daniel, G. L., D'Emilia, J. C., Rodriguez-Bigas, M., Suh, O. K., Brewer, D. A., Fung, C., Chapuis, P., Bokey, E. L., Garcia, J. C., Banerjee, S., Remzi, F. H., Lavery, I. C., Jorge, J. M. N., Ger, G. C., Gonzalez, L., Gee, A. S., Roe, A. M., Durdey, P., Kaye, M. D., Kyzer, S., Gordon, P. H., Hasegawa, M., Bun, P. Tae, Ikeuchi, D., Onodera, H., Imamura, M., Maetani, S., Blake, T., Hellinger, M., Grewal, H., Klimstra, D. S., Cohen, A. M., Guillem, J. G., Rooney, P. S., Gifford, K. -A., Clarke, P. A., Kuhn, J. A., Bryce, K., Frank, N., Dignan, R. D., Lichliter, W. E., Franko, E., Jacobson, R. M., Preskitt, J. T., Lieberman, Z., Tulanon, P., Steinbach, H., McCarty, T., Simons, T., Plasencia, G., Viamonte, M., Wiltz, O., Jacobs, M., Chen, W. S., Leu, S. Y., Hsu, H., Bessler, M., Halverson, A., Kayton, M. L., Treat, M. R., Nowygrod, R., Congilosi, S., Madoff, R., Wong, W. D., Rothenberger, D., Buie, W. D., Paterson, R., Cartmill, J. A., Trokel, M. J., Gingold, B. S., Cooper, M., Gorfine, S. R., Bauer, J. J., Gelernt, I. M., Kreel, I., Harris, M. T., Vallejo, J. F., Kestenberg, A., Miyajima, N., Kano, N., Ishikawa, Y., Sakai, S., Yamakawa, T., Otchy, D. P., Van Heerden, J. A., Ilstrup, D. M., Weaver, A. L., Winter, L. D., Mav, J., Lee, P. Y., Vetto, J. T., Sullivan, E. S., Rabkin, J., Mayoral, J. L., Matas, A. J., Bove, P., Visser, T., Barkel, D., Villalba, M., Bendick, P., Glover, J., Golub, R. W., Cirocco, W. C., Daniel, N., Altringer, W., Domingues, J. M., Brubaker, L. T., Smith, C. S., Kumar, S., and Gilbert, P.

Published
1994
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18. Acute irradiation causes a long-term disturbance in the heterogeneity and gene expression profile of medullary thymic epithelial cells

Author

Kenta Horie, Kano Namiki, Kyouhei Kinoshita, Maki Miyauchi, Tatsuya Ishikawa, Mio Hayama, Yuya Maruyama, Naho Hagiwara, Takahisa Miyao, Shigeo Murata, Tetsuya J. Kobayashi, Nobuko Akiyama, and Taishin Akiyama

Subjects
thymus, thymic epithelial cell (TEC), AIRE, radiation, scRNA seq, Immunologic diseases. Allergy, RC581-607
Abstract

The thymus has the ability to regenerate from acute injury caused by radiation, infection, and stressors. In addition to thymocytes, thymic epithelial cells in the medulla (mTECs), which are crucial for T cell self-tolerance by ectopically expressing and presenting thousands of tissue-specific antigens (TSAs), are damaged by these insults and recover thereafter. However, given recent discoveries on the high heterogeneity of mTECs, it remains to be determined whether the frequency and properties of mTEC subsets are restored during thymic recovery from radiation damage. Here we demonstrate that acute total body irradiation with a sublethal dose induces aftereffects on heterogeneity and gene expression of mTECs. Single-cell RNA-sequencing (scRNA-seq) analysis showed that irradiation reduces the frequency of mTECs expressing AIRE, which is a critical regulator of TSA expression, 15 days after irradiation. In contrast, transit-amplifying mTECs (TA-mTECs), which are progenitors of AIRE-expressing mTECs, and Ccl21a-expressing mTECs, were less affected. Interestingly, a detailed analysis of scRNA-seq data suggested that the proportion of a unique mTEC cluster expressing Ccl25 and a high level of TSAs was severely decreased by irradiation. In sum, we propose that the effects of acute irradiation disrupt the heterogeneity and properties of mTECs over an extended period, which potentially leads to an impairment of thymic T cell selection.

Published
2023
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19. Influence of current modulation waveform on polycrystalline diamond film deposition using modulated induction thermal plasmas—numerical and experimental studies.

Author

Hata, Kazufumi, Tanaka, Yasunori, Kano, N, Nakano, Y, and Ishijima, T

Subjects
THERMAL plasmas, NUMERICAL calculations, NUCLEATION
Abstract

In this paper, the influence of amplitude-modulated coil current waveform on polycrystalline diamond deposition was studied using modulated induction thermal plasma (M-ITP) with numerical and experimental approaches. The M-ITP is useful in undertaking the nucleation of diamond particles necessary for the first stage of diamond film deposition. First, numerical thermo-fluid calculations were conducted for Ar M-ITP with CH4/H2 feedstock gas to investigate the influence of a modulation waveform on particle fluxes of different hydrocarbon species onto a Si substrate. Furthermore, experiments were performed to fabricate polycrystalline diamond film deposition using M-ITP with different modulation waveforms. The modulation waveform for the coil current was set as a rectangular waveform, a saw-tooth waveform and a reverse saw-tooth waveform in the calculations and the experiments. The experimental results showed that the saw-tooth M-ITP provided a higher deposition rate, of 2.05 µm h−1, than other waveforms. This could be attributed to the higher fluxes of neutral hydrocarbons in the saw-tooth M-ITP according to the calculation results. [ABSTRACT FROM AUTHOR]

Published
2021
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21. Simulation Methodology in Construction Process

Author

Kano, N., Bijl, A., Akin, O., Chen, C.-C., Dave, B., Pithavadian, S., Kalay, Y. E., Harfmann, A. C., Swerdloff, L. M., Krishnamurti, R., Schmitt, G., Robert, J.-C., Weeks, J., Flemming, U., Coyne, R., Glavin, T., Rychener, M., Koskela, L., Hynynen, R., Kallavuo, M., Kahkönen, K., Salokivi, J., Bridges, A. H., Polistina, A., Whittaker, W. L., Hasegawa, Y., Abel, C., Slocum, A. H., Kangari, R., Bandari, E., Wanner, M.-C., Skibniewski, M., Derrington, P., Hendrickson, C., Woodbury, R. F., Keirouz, W. T., Oppenheim, I. J., Rehak, D. R., Earl, C. F., Kano, N., Crowley, J. L., Drazan, P. J., Motazed, B., Oeser, H.-R., Tanaka, N., Saito, M., Arai, K., Banno, K., Ochi, T., Kikuchi, S., Ueno, T., Maeda, J., Yoshida, T., and Suzuki, S.

Published
1986
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22. Chemical and isotopic compositions in acid residues from various meteorites

Author

Kano, N, Yamakoshi, K, Matsuzaki, H, and Nogami, K

Subjects
Astrophysics
Abstract

We are planning to carry out systematic isotopic investigations of Ru, Mg, etc., in primordial samples. The investigations will be pursued in the context of a study of the pre-history of the solar system. It is hoped that the study will yield direct evidence for processes of nucleosynthesis in the pre-solar stage and detection of extinct radioactive nuclides. In this paper, we present the results of chemical compositions of acid residues obtained from three types of meteorites: Canyon Diablo (IA), Allende (CV3), and Nuevo Mercuro (H5); and the preliminary results of Ru isotopic compositions.

Published
1993

23. Formation and Detection of Hydrogen by Oxygen Discharge Using Oxygen Pump-Sensor

Author

Michihisa Fukumoto and Kano Nakajima

Subjects
hydrogen, water vapor, oxygen partial pressure, solid electrolyte, oxygen pump sensor, Science (General), Q1-390
Abstract

An oxygen pump sensor was constructed using yttria-stabilized zirconia, which is an oxide ion conductor, and oxygen was discharged from steam to generate hydrogen. The oxygen pump sensor consisted of a pump that discharges oxygen and a sensor that controls the oxygen partial pressure by having electrodes in two places. Oxygen was discharged by applying a current to the pump by controlling the potential of the sensor. Hydrogen was then generated from water vapor. Furthermore, an oxygen pump sensor was installed in the second stage, oxygen was supplied by the pump, and the amount of generated hydrogen was measured in situ. This measurement showed that the oxygen partial pressure of the atmosphere decreased as hydrogen was generated. Specifically, the partial pressure of the water vapor generated more hydrogen at 30.8 vol.% than at 12.2 vol.%. Moreover, the amounts of oxygen discharged and hydrogen generated inversely correlated with the potential.

Published
2022
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29. Electrocatalytic Performance of Ethanol Oxidation on Ni and Ni/Pd Surface-Decorated Porous Structures Obtained by Molten Salts Deposition/Dissolution of Al-Ni Alloys

Author

Dawid Kutyła, Kano Nakajima, Michihisa Fukumoto, Marek Wojnicki, and Karolina Kołczyk-Siedlecka

Subjects
porous Ni, molten salts electrodeposition, galvanic displacement reaction, ethanol oxidation, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

Ni coatings with high catalytic efficiency were synthesised in this work, obtained by increasing the active surface and modifying Pd as a noble metal. Porous Ni foam electrodes were obtained by electrodeposition of Al on a nickel substrate. Deposition of Al was carried out with potential −1.9 V for a time of 60 min in NaCl–KCl-3.5 mol%AlF3 molten salt mixture at 900 °C, which is connected with the formation of the Al-Ni phase in the solid state. Dissolution of Al and Al-Ni phases was performed by application of the potential −0.5 V, which provided the porous layer formation. The obtained porous material was compared to flat Ni plates in terms of electrocatalytic properties for ethanol oxidation in alkaline solutions. Cyclic voltammetry measurements in the non-Faradaic region revealed the improvement in morphology development for Ni foams, with an active surface area 5.5-times more developed than flat Ni electrodes. The catalytic activity was improved by the galvanic displacement process of Pd(II) ions from dilute chloride solutions (1 mM) at different times. In cyclic voltammetry scans, the highest catalytic activity was registered for porous Ni/Pd decorated at 60 min, where the maximum oxidation peak for 1 M ethanol achieved +393 mA cm−2 compared to the porous unmodified Ni electrode at +152 mA cm−2 and flat Ni at +55 mA cm−2. Chronoamperometric measurements in ethanol oxidation showed that porous electrodes were characterised by higher catalytic activity than flat electrodes. In addition, applying a thin layer of precious metal on the surface of nickel increased the recorded anode current density associated with the electrochemical oxidation process. The highest activity was recorded for porous coatings after modification in a solution containing palladium ions, obtaining a current density value of about 55 mA cm−2, and for a flat unmodified electrode, only 5 mA cm−2 after 1800 s.

Published
2023
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30. CAD and Robotics in Architecture and Construction

Author

Bijl, A., primary, Akin, O., additional, Chen, C.-C., additional, Dave, B., additional, Pithavadian, S., additional, Kalay, Y. E., additional, Harfmann, A. C., additional, Swerdloff, L. M., additional, Krishnamurti, R., additional, Schmitt, G., additional, Robert, J.-C., additional, Weeks, J., additional, Flemming, U., additional, Coyne, R., additional, Glavin, T., additional, Rychener, M., additional, Koskela, L., additional, Hynynen, R., additional, Kallavuo, M., additional, Kahkönen, K., additional, Salokivi, J., additional, Bridges, A. H., additional, Polistina, A., additional, Whittaker, W. L., additional, Hasegawa, Y., additional, Abel, C., additional, Slocum, A. H., additional, Kangari, R., additional, Bandari, E., additional, Wanner, M.-C., additional, Skibniewski, M., additional, Derrington, P., additional, Hendrickson, C., additional, Woodbury, R. F., additional, Keirouz, W. T., additional, Oppenheim, I. J., additional, Rehak, D. R., additional, Earl, C. F., additional, Kano, N., additional, Crowley, J. L., additional, Drazan, P. J., additional, Motazed, B., additional, Oeser, H.-R., additional, Tanaka, N., additional, Saito, M., additional, Arai, K., additional, Banno, K., additional, Ochi, T., additional, Kikuchi, S., additional, Ueno, T., additional, Maeda, J., additional, Yoshida, T., additional, and Suzuki, S., additional

Published
1986
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31. Assembling Wall Panels with Robotic technologies

Author

Gassel, van, F.J.M., Schrijver, P., Lichtenberg, J.J.N., Kano, N., and Research Performance engineering for Built Environments

Abstract

Robots are only incidentally used to assemble wall panels in high-rise buildings, even though robotic technologies for various applications are available. These applications can improve construction site safety and increase the productivity of the assembly process. A research project initiated at Eindhoven University of Technology (TU e) in the Netherlands aims to develop an integral design for a curtain wall. The curtain wall’s assembly, disassembly and user functions are integrated into a single concept. The focus lies on the assembly disassembly process and the use ofnew robotic technologies. This paper presents the initial results of a survey of currently available strategies for the assembly of curtain wall systems, a description of the functions and the design requirements. The purpose of this research is to explore the limits of currently available robotic technologies in designing a curtain wall for the entire life cycle.

Published
2006

41. Direct transfer of bovine embryos frozen-thawed in the presence of propylene glycol or ethylene glycol under on-farm conditions in an integrated embryo transfer program

Author

Dochi, O, primary, Yamamoto, Y, additional, Saga, H, additional, Yoshiba, N, additional, Kano, N, additional, Maeda, J, additional, Miyata, K, additional, Yamauchi, A, additional, Tominaga, K, additional, Oda, Y, additional, Nakashima, T, additional, and Inohae, S, additional

Published
1998
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