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Additional file 1: Figure S1. Cross-linking assay using BSA as a substrate after incubation for 120 min with several volumes of SmTG solution extracted from the BY4741-TG strain. Lane 1, molecular size marker; lane 2, BSA only; lanes 3, 4 and 5, 1×, 5× and 10×SmTG (+BSA), respectively; lanes 6, 7 and 8, 1×, 5× and 10×SmTG (−BSA), respectively. Figure S2. Effect of adding reduced glutathione to polymerization of caseinate by SmTG. SDS-PAGE profiles show the protein pattern of caseinate after incubation with SmTG. 1×SmTG extracted from the BY4741-TG strain was used. Lane 1, molecular size marker; lane 2, caseinate only; lanes 3, 4, 5, 6, 7 and 8, caseinate, SmTG and 0, 0.2, 0.4, 0.8, 1.6 and 3.2 mM glutathione, respectively; lane 9, SmTG only. The polymerized caseins (molecular weight > 100 kDa) presented in the top panel were recovered and measured as shown in Fig. 2. Figure S3. Growth and glutathione production of S. cerevisiae expressing SmTG. (a) Time course of cell growth. Solid and dotted lines represent the BY4741-TG and GCI-TG strains, respectively. (b) Glutathione concentrations in 1×SmTG solutions extracted from the BY4741-TG strain (black) and GCI-TG strain (white). (c) Expression level of SmTG after cultivation for 24 h. lane 1, BY4741-TG strain; lane 2, GCI-TG strain. Expression level of SmTG was calculated from the intensity of each SmTG band and represented as relative values (%). The values are means and the error bars show the SD (n = 3).

Additional file 1. Table S1. Effect of glycine addition on intracellular metabolites in HEM1-overexpressing S. cerevisiae. Figure S1. Relative mRNA levels in HEM1-, HEM1/ACO1- and HEM1/ACO2-overexpressing strains.

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Emi Mashima, Akiha Inoue, Yumiko Sakuragi, Takashi Yamaguchi, Natsuko Sasaki, Yoko Hara, Daisuke Omoto, Shun Ohmori, Sanehito Haruyama, Yu Sawada, Manabu Yoshioka, Daisuke Nishio, Motonobu Nakamura Department of Dermatology, University of Occupational andEnvironmental Health, Kitakyushu,Japan Abstract: Nivolumab was developed as a monoclonal antibody against programmed death receptor-1, an immune checkpoint inhibitor which negatively regulates T-cell proliferation and activation. Intravenous administration of nivolumab was approved for the treatment of unresectable malignant melanoma in 2014 in Japan. When advanced melanoma patients were treated with nivolumab, median overall survival became longer. Overall survival rate was significantly better in nivolumab-treated melanoma patients than dacarbazine-treated melanoma patients. Nivolumab had an acceptable long-term tolerability profile, with 22% of patients experiencing grade 3 or 4 adverse events related to the drug. Therefore, nivolumab can become an alternative therapy for advanced malignant melanoma. Keywords: monoclonal antibody, PD-1, PD-L1

application/pdf, 紀要論文, 現在、閉経／更年期は「生殖期から非生殖期への移行」と定義づけられているが、この捉え方はきわめて近代的なものである。本稿では、閉経／更年期概念が成立する以前のドイツ18世紀前半を例にとり、そこにおける「月経の閉止」の意味づけを検証している。考察に当たっては、Barbara Dudenの『女の皮膚の下』（1987=1994）の枠組みに依拠し、Johann Storchの『婦人病』を史料としている。Storchの著作にあらわれている月経観についてはDudenがすでに考察しているが、さらに「月経の閉止」の意味にまで踏みこむと、どのようなことが言えるのか。結論として、月経の閉止は「フルス／流れ」が滞ることによる危険な時であるが、月経の閉止による「再生産／非再生産」の境界は曖昧なものであること、また現代的な「更年期」の概念はないことが見出された。, Menopause, or climacteric, is defined as the phase in the aging of women that marks the transition from the reproductive phase to the non-reproductive phase. However, this is a very modern definition. How was menopause or climacteric defined in the preindustrial society? This paper attempts to understand how menopause was defined in early eighteenth-century Germany. The framework of the discussion relies on the work of Barbara Duden, who clarified the understanding that a physician and his patients had about the human body, in northern Germany around the year 1730. In conclusion, menopause was identified as being a rather critical point in a woman's life as opposed to an obvious transition between reproduction and non-reproduction, and no “menopausal disorder”?in the modern sense?was experienced by the women of that period.