The Evolution of Corporate Governance in Japan: The Continuing Relevance of Berle and Means

The evolution of corporate governance in Japan towards international standards continues, though at a gradual pace that often concerns outsiders. The substance of Japanese corporate governance is often questioned due to a lack of understanding of the unique elements of the Japanese institutional system. Japanese companies are under a sustained assault from overseas investors to introduce a greater number of independent directors on boards, improve accountability, and enhance transparency. The majority of Japanese companies have taken what they regard as significant steps in this direction of accountability. In Japan, however, there is a different conception of the role of the board, the function of corporate governance, and the purpose of the corporation. This Article argues that significant change in these enduring Japanese corporate values and practices can only be accomplished if a more convincing theory and model of the corporation is proposed

The Evolution of Corporate Governance in Japan: The Continuing Relevance of Berle and Means

The evolution of corporate governance in Japan towards international standards continues, though at a gradual pace that often concerns outsiders. The substance of Japanese corporate governance is often questioned due to a lack of understanding of the unique elements of the Japanese institutional system. Japanese companies are under a sustained assault from overseas investors to introduce a greater number of independent directors on boards, improve accountability, and enhance transparency. The majority of Japanese companies have taken what they regard as significant steps in this direction of accountability. In Japan, however, there is a different conception of the role of the board, the function of corporate governance, and the purpose of the corporation. This Article argues that significant change in these enduring Japanese corporate values and practices can only be accomplished if a more convincing theory and model of the corporation is proposed

フルクトースの経口投与はラット脂肪性肝炎モデルにおいて腸管透過性亢進作用を介して肝線維化および肝発癌を悪化させる

Recent reports have revealed the impact of a western diet containing large amounts of fructose on the pathogenesis of non-alcoholic steatohepatitis (NASH). Fructose exacerbates hepatic inflammation in NASH by inducing increasing intestinal permeability. However, it is not clear whether fructose contributes to the progression of liver fibrosis and hepatocarcinogenesis in NASH. The aim of this study was to investigate the effect of fructose intake on NASH in a rat model. A choline-deficient/L-amino acid diet was fed to F344 rats to induce NASH. Fructose was administrated to one group in the drinking water. The development of liver fibrosis and hepatocarcinogenesis were evaluated histologically. Oral fructose administration exacerbated liver fibrosis and increased the number of preneoplastic lesions positive for glutathione S-transferase placental form. Fructose-treated rats had significantly higher expression of hepatic genes related to toll-like receptor-signaling, suggesting that fructose consumption increased signaling in this pathway, leading to the progression of NASH. We confirmed that intestinal permeability was significantly higher in fructose-treated rats, as evidenced by a loss of intestinal tight junction proteins. Fructose exacerbated both liver fibrosis and hepatocarcinogenesis by increasing intestinal permeability. This observation strongly supports the role of endotoxin in the progression of NASH.博士（医学）・乙第1432号・令和元年9月27日Copyright © 2018 Impact Journals, LLCCopyright © Seki et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0 https://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

スルフォラファンの肝癌発育抑制効果および血管新生抑制効果に関する基礎的検討

Sulforaphane (SFN) exhibits inhibitory effects in different types of cancers. However, its inhibitory effect on liver cancer remains unknown. This study aimed to determine the therapeutic potential of SFN for the treatment of liver cancer and explore the functional mechanisms underlying the inhibitory effects of SFN. Water-Soluble Tetrazolium salt (WST-1) assay was performed to assess the in vitro effect of SFN on cell proliferation in the human liver cancer cell lines, HepG2 and Huh-7. The mRNA levels of Nrf2 target genes and cell cycle-related genes were determined using quantitative RT-PCR. For assessing the inhibitory effect of SFN in vivo, we injected immortalized liver cancer cells into BALB/c nude mice as a xenograft model. SFN was orally administrated daily after tumor inoculation and continued for thirty-five days until their sacrifices. Nrf2 activation, induced by SFN, was confirmed by mRNA upregulation of HO-1, MRP2, and NQO1 in both the cell lines. Significant inhibition of liver cancer cell proliferation by SFN was shown in vitro in a dose-dependent manner by the downregulation of CCND1, CCNB1, CDK1 and CDK2. In in vivo studies, the administration of SFN significantly reduced the subcutaneous tumor burdens at the end of experiments by suppressing tumor cell proliferation, confirmed by Ki67 immunohistochemical analysis. The mRNA levels of CCND1, CCNB1, CDK1 and CDK2 were also decreased in these SFNtreated xenograft tumors. Moreover, CD34 immunostaining elucidated that the intratumoral neovascularization was markedly attenuated in the SFN-treated xenograft tumors. SFN exerts inhibitory effect on human liver cancer cells with antiangiogenic activity. The earlier version of this study was presented at the meeting of AASLD Liver Learning on Oct 2017.博士（医学）・甲第707号・平成31年3月15日© The Author(s) 2018 Under License of Creative Commons Attribution 3.0 License https://creativecommons.org/licenses/by/3.0

肝線維化に対するファルネソイドX受容体アゴニストとジペプチジルペプチダーゼ-4阻害薬の併用効果

Aim: Non-alcoholic steatohepatitis (NASH) has a broad clinicopathological spectrum (inflammation to severe fibrosis). The farnesoid X receptor agonist obeticholic acid (OCA) ameliorates the histological features of NASH; satisfactory antifibrotic effects have not yet been reported. Here, we investigated the combined effects of OCA + a dipeptidyl peptidase-4 inhibitor (sitagliptin) on hepatic fibrogenesis in a rat model of NASH. Methods: Fifty Fischer 344 rats were fed a choline-deficient L-amino-acid-defined (CDAA) diet for 12 weeks. The in vitro and in vivo effects of OCA + sitagliptin were assessed along with hepatic fibrogenesis, lipopolysaccharide-Toll-like receptor 4 (TLR4) regulatory cascade and intestinal barrier function. Direct inhibitory effects of OCA + sitagliptin on activated hepatic stellate cells (Ac-HSCs) were assessed in vitro. Results: Treatment with OCA + sitagliptin potentially inhibited hepatic fibrogenesis along with Ac-HSC proliferation and hepatic transforming growth factor (TGF)-β1, α1(I)-procollagen, and tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA expression and hydroxyproline levels. Obeticholic acid inhibited hepatic TLR4 expression and increased hepatic matrix metalloproteinase-2 expression. Obeticholic acid decreased intestinal permeability by ameliorating CDAA diet-induced zonula occludens-1 disruption, whereas sitagliptin directly inhibited Ac-HSC proliferation. The in vitro suppressive effects of OCA + sitagliptin on TGF-β1 and α1(I)-procollagen mRNA expression and p38 phosphorylation in Ac-HSCs were almost consistent. Sitagliptin directly inhibited the regulation of Ac-HSC. Conclusions: Treatment with OCA + sitagliptin synergistically affected hepatic fibrogenesis by counteracting endotoxemia induced by intestinal barrier dysfunction and suppressing Ac-HSC proliferation. Thus, OCA + sitagliptin could be a promising therapeutic strategy for NASH.博士（医学）・甲第737号・令和2年3月16日© 2019 The Japan Society of HepatologyThis is the peer reviewed version of the following article: [https://onlinelibrary.wiley.com/doi/full/10.1111/hepr.13385], which has been published in final form at [https://doi.org/10.1111/hepr.13385]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions

J. 高分子中に取り込まれた水の高周波分光法による状態分析 : 水と安全の科学

製作した高周波分光装置において、横軸を周波数、縦軸を共振強度にとったスペクトルとして観測すると、物質中の水の束縛状態に対応すると考えられる位置にピークが現れ、かつ、混合比を変えるとピークがシフトする、すなわち水の状態分析ができることが判明した。これを、衝撃吸収剤の原料の一つであるポリオールに適用した。その結果、束縛状態の異なる3種の水の存在を確認することができ、これは熱測定(DSC)による結果と一致するものであった。とくに本法では測定温度を変えることなく常温の実験のみでDSCと同じ結果が得られたことが特徴といえる。この成果を踏まえ、さらに各種の試料につき試験的な測定を行た。たとえば、エチレンオキシドーヒドロキノンの系、エチレンービニルアルコール共重合膜の系、コロイダルシリカ(石油分留用のゼオライトを合成するときの前駆体)の反応過程、等々である。いずれも興味ある知見を与えそうなスペクトルを得ることができ、目下、さらなる研究の具体策を検討中である

Reductive C–O Silylation by Rhodium/Lanthanum Cooperative Catalysis

In the realm of synthetic organic chemistry, a transformation enabling access to high-value-added compounds from readily available starting materials is the most ideal. Cross-electrophile coupling (XEC) reactions, the coupling of two different electrophiles, are of great importance in terms of the variety and availability of electrophiles compared with common nucleophiles. Among various electrophiles, phenols and aryl ethers can be particularly useful aryl electrophiles owing to their low toxicity, robustness, and availability. However, XEC of phenols and aryl ethers remains elusive because it is generally challenging to distinguish between two electrophiles and selectively obtain cross-coupling products under harsh reaction conditions that are often required for the activation of the less reactive C–O bonds. Meanwhile, chlorosilanes are easily available and serve as silicon electrophiles to access the most known organosilicon compounds through coupling with organic nucleophiles. Considering the utility of organosilicon compounds as organic materials and building blocks for organic synthesis, the XEC of phenols and chlorosilanes can be a highly practical and useful transformation but has never been viable. Here we describe the XEC of phenol and alcohol derivatives with chlorosilanes by cooperative rhodium and lanthanum catalysis. This reaction allows a range of anisole derivatives as well as benzylic ethers, phenols, benzylic alcohols, allylic ethers, and allylic alcohols to be transformed into various organosilicon compounds in a single step. Mechanistic studies including kinetics, stoichiometric organometallic reactions, XAS, and theoretical calculations suggest a heterobimetallic complex bearing a Rh–Mg and/or Rh–La bond as a key catalytically active species. This method can be applied to the development of novel silicon- containing organic materials and drugs containing silicon as a carbon isostere. On the other hand, the XEC of phenol derivatives enables the use of biomass-derived resources as an alternative to petroleum to produce useful compounds in a sustainable manner

Proposal of a novel AI-based plant operator support system for the safety of nuclear power plants

Enhancing the ability to manage abnormal situations is important for improvement of the safety of nuclear power plants. It is necessary to investigate potential risks thoroughly in advance, and prepare countermeasures against the identified risks. In addition, in case of an occurrence of an abnormal situation, plant operators are required to recognize the plant situation promptly and select a suitable countermeasure. However, the human ability to perform it is limited because the number of such abnormal situations in actual nuclear power plants is indefinite. Due to the advent of AI, it becomes possible to compensate for such limitation, by learning abnormal situations and assessing the effectiveness of prepared countermeasures virtually. The present study aims to develop such an AI-based support system for the plant operators to deal with abnormal situations steadily. Although many previous studies about detection of anomalies have been conducted, few studies consider countermeasures, especially against unexperienced abnormal situations. This study develops a novel plant operator support system designed not only to estimate details of anomalies in a plant but also propose countermeasures adaptively by employing several AI technologies of deep neural network and reinforcement learning. A plant simulator is used to prepare training data for the AI system. The combination of the proposed AI-based system and the plant simulator makes it possible to identify abnormal situations unknown to operators and propose countermeasures. The design and performance of the proposed system is illustrated using High Temperature engineering Test Reactor (HTTR) operated in Japan Atomic Energy Agency