Dapagliflozin was well tolerated and showed predictable dose-proportional PK and PD parameters in both healthy and T2DM Japanese subjects.

The cellular aging-associated transcriptional repressor that we previously named as Orpheus was identical to Oct-1, a member of the POU domain family. Oct-1 represses the collagenase gene, one of the cellular aging-associated genes, by interacting with an AT-rich cis-element in the upstream of the gene in preimmortalized cells at earlier population-doubling levels and in immortalized cells. In these stages of cells, considerable fractions of the Oct-1 protein were prominently localized in the nuclear periphery and colocalized with lamin B. During the cellular aging process, however, this subspecies of Oct-1 disappeared from the nuclear periphery. The cells lacking the nuclear peripheral Oct-1 protein exhibited strong collagenase expression and carried typical senescent morphologies. Concomitantly, the binding activity and the amount of nuclear Oct-1 protein were reduced in the aging process and resumed after immortalization. However, the whole cellular amounts of Oct-1 protein were not significantly changed during either process. Thus, the cellular aging-associated genes including the collagenase gene seemed to be derepressed by the dissociation of Oct-1 protein from the nuclear peripheral structure. Oct-1 may form a transcriptional repressive apparatus by anchoring nuclear matrix attachment regions onto the nuclear lamina in the nuclear periphery.

The reaction of carbon dioxide (CO 2 ) on Zn-deposited copper surfaces was systematically investigated by ambient-pressure X-ray photoelectron spectroscopy (AP-XPS). In the presence of 0.8 mbar CO 2 and 0.4 mbar H 2 gases, hydrogenation products are not observed; only carbonate is formed on Zn-deposited Cu(111) and Cu( 997) surfaces. The formation rate of carbonate at 299 K is significantly faster on Zn/Cu(997) than that on Zn/Cu(111), indicating step sites are more reactive for CO 2 activation than terrace sites. On the other hand, the addition of water in the feed gas leads to hydrogenation of CO 2 to formate at sample temperatures around 400 K. This suggests that hydroxyl produced from dissociative adsorption of water is a source for the CO 2 hydrogenation observed under the present reaction conditions. The reaction products such as carbonate and formate on the Zn/Cu(997) surface are more stable than those on the bare Cu(997) surface. In particular, formate remains on Zn-deposited Cu surfaces up to 473 K, which is close to the operation temperature of industrial Cu-ZnO catalysts. Therefore, one of the roles of Zn atoms on Cu surfaces is the stabilization of reaction intermediates formed from CO 2 .

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