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Hokkaido Univ, Lab Clin Pharmaceut & Therapeut, Div Biopharmaceut Sci & Pharm,Fac Pharmaecut Sci, Dept Biopharmaceut Sci & Pharm,Kita Ku, Sapporo, Hokkaido 0600812, Japan Hokkaido Univ, Lab Clin Pharmaceut & Therapeut, Div Biopharmaceut Sci & Pharm,Fac Pharmaecut Sci, Dept Biopharmaceut Sci & Pharm,Kita Ku, Sapporo, Hokkaido 0600812, Japan