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Journal Articles

Anti-FGF23 neutralizing antibodies show the physiological role and structural features of FGF23

Yamazaki, Yuji*; Tamada, Taro; Kasai, Noriyuki*; Urakawa, Itaru*; Aono, Yukiko*; Hasegewa, Hisashi*; Fujita, Toshiro*; Kuroki, Ryota; Yamashita, Takeyoshi*; Fukumoto, Seiji*; et al.

Journal of Bone and Mineral Research, 23(9), p.1509 - 1518, 2008/09

 Times Cited Count:149 Percentile:94.58(Endocrinology & Metabolism)

Fibroblast growth factor (FGF)23 is proposed to play a physiological role in the regulation of phosphate and vitamin D metabolism; deranged circulatory levels of FGF23 cause several diseases with abnormal mineral metabolism. We developed two antibodies (FN1 and FC1) that recognize the N- and C-terminal regions of FGF23, respectively. Both FN1 and FC1 inhibited FGF23 activity in a cell-based Klotho-dependent reporter assay. The present study using neutralizing antibodies confirms that FGF23 is a physiological regulator of phosphate and vitamin D metabolism. Then, we addressed the mechanism of action for these neutralizing antibodies. Structural analysis of the FGF23/FN1-Fab complex revealed that FN1 masked putative FGF receptor-binding sites in the N-terminal domain of FGF23, while biochemical analyses showed that FC1 interfered with the association between FGF23 and Klotho by binding to the C-terminal domain of FGF23. Taken together, our results suggest that the N- and C-terminal domains of FGF23 are responsible for association with cognate FGF receptors and Klotho, respectively, and that these interactions are indispensable for FGF23 activity.

Oral presentation

MOX fuel fabrication technology in J-MOX

Osaka, Shuichi*; Yoshida, Ryoichi*; Yamazaki, Yukiko*; Ikeda, Hiroyuki*

no journal, , 

Japan Nuclear Fuel Ltd. (JNFL) has constructed JNFL MOX Fuel Fabrication Plant (J-MOX) since 2010. The MIMAS process has been introduced in the powder mixing process from AREVA NC considering a lot of MOX fuel fabrication experiences at MELOX plant in France. The feed material of Pu for J-MOX is MH-MOX powder from Rokkasho Reprocessing Plant (RRP) in Japan. The MH-MOX powder is a mixed oxide consisting of 50 wt% plutonium oxide and 50 wt% uranium oxide produced by direct denitration of Pu and U nitric acid solution utilizing microwave heating (MH) technology which was developed by Japan Atomic Energy Agency (JAEA). The compatibility of the MH-MOX powder with the MIMAS process was positively evaluated and confirmed in our previous study. The MIMAS process has two mixing steps. In the first step, which is called "Primary Blend", the feed materials (MH-MOX powder, UO$$_{2}$$ powder and recycled scrap powder) are mixed and homogeneous powder which contains approximately 30 wt% of Pu is obtained. In the second step, which is called "Secondary Blend", the primary blend powder is diluted with UO$$_{2}$$ powder to a certain Pu content. This paper describes the influences of the UO$$_{2}$$ powder and the recycled scrap powder on the MOX pellet density.

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