Phosphatidylinositol 3-kinase (PI 3-kinase) is a key enzyme in the signaling pathways of 3-phosphorylated polyphosphoinositides. The natural PI purified from bovine liver, which mainly contains arachidonate at the sn-2 position, is an excellent substrate of PI 3-kinase. However, synthetic distearate PI and synthetically hydrogenated natural PI were not phosphorylated by PI 3-kinase. In this study, phosphatidylinositols with saturated sn-2 fatty acids were evaluated the phosphorylation reaction with PI 3-kinase. A standard fatty acids mixture of PI [PI(C4)〜PI(C16)] at the sn-2 center was synthesized from an equimolar mixture of seven carboxylic acids (C4, C6, C8, C10, C12, C14, C16), and the PI mixture was subjected to the enzymatic reaction with PI 3-kinase. Negative ion fast atom bombardment (FAB) mass spectrometric analysis of the reaction mixture using a matrix (triethanolamine: glycerol=3: 1) showed the apparent ion peaks of monophosphorylated PI(C4), PI(C6) and PI(C8) analogs. Short sn-2 fatty acid analogs such as PI(4) and PI(C8) were proved to be excellent substrates of PI 3-kinase by means of independent phosphorylation experiments with sythetic PI. In these experiments, after PI 3-kinase reaction of the synthetic PI with [γ-^<32>P]-ATP, the resulting phosphorylated products were analyzed by TLC. The present results open a new window on the design of phosphatidylinositols with saturated sn-2 fatty acids, which are apparently more stable than natural ones.

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抗体薬物複合体（ADC）は創薬標的となる抗原に対して特異的に結合する抗体を運搬役とし、薬物がもつ最大の薬効を発揮するバイオ医薬品である。筆者らが創製したトラスツズマブデルクステカン（T-DXd, DS-8201a）は、DNAトポイソメラーゼⅠ阻害剤であるカンプトテシン誘導体を腫瘍細胞内で切断可能なリンカーを介して抗HER2抗体に結合している。その主な特徴は、1つの抗体あたりの薬物結合比が高く均一性が高いこと、バイスタンダー効果によるヘテロな腫瘍への強力な薬効を有すること、そして循環中に安定であることから安全性の懸念が少ないことがあげられ、HER2発現ヒトがん細胞株の異種間移植マウスモデルに対して強力な抗腫瘍効果を示した。現在、HER2陽性乳がん、HER2低発現乳がん、HER2陽性胃がん、その他のがん腫に対する第2相、第3相の臨床試験を実施中である。

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  Results of the wavelet analysis of noise generated during the shake-out of iron castings using self-hardening mold showed that the frequency spectrum right after the start of shake-out is close to that of the consolidated vibration of the shake-out machine and molding flask. On the other hand, after shakeout completes, the frequency spectrum closely resembles the characteristic frequency of the molding flask.
  Based on these analytical results, we developed a measurement system for determining the shake-out ending time. The measurement system consists of a filter, rectifier, differential, AND circuit and amplifier. We determined the ending time of the shake-out process using this system by applying noise as its input. The obtained results agreed well with that obtained by visual inspection.

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Phosphatidylinositol 3,4,5-trisphosphate (PIP_3: 1) is a polyphosphoinositide produced from phosphatidylinositol 4,5-bisphosphate (PI4, 5P_2) by phosphatidylinositol-3 kinase (PI-3 kinase) in response to a wide range of growth factor stimulation. It is still unclear what a important role of PIP_3 is. To investigate how PIP_3 interact with proteins in the intracellular signal transduction system, we have developed two affinity gels with novel PIP_3 analogs. IP_3-APBgel is a affinity gel bearing 1-O-acyl type ligand (IP_3-APB: 6) and is expected to associate with proteins which specifically recognize head group of PIP_3. Using this IP_3-APBgel, we have isolated a novel protein with a molecular mass of 43kD from bovine brain extract and was termed PIP_3 binding protein. The protein bound PIP_3 with a higher affinity than it did inositol 1,3,4,5-tetrakisphosphate (IP_4), PI4, 5P_2, phosphatidylinositol 3,4-bisphosphate (PI3, 4P_2) and phosphatidylinositol 3-phosphate (PI3P), suggesting that the binding to PIP_3 was specific. It contained one zinc finger motif and two pleckstrin homology (PH) domains and the entire sequence was 83% similar to centaurin α, another PIP_3 binding protein. The binding activity was weaker in the mutants with a point mutation in the conserved sequences in each PH domains and the introduction of both mutations caused loss of the binding activity. These suggest PIP_3BP binds PIP_3 throuth two PH domains present in the molecule. To detect PIP_3 binding proteins in a more exact manner, we designed PIP_3 analog containing a glycerol group as well as fatty acid groups (PIP_3-APB: 12). One of the peptides identified from the lysates of calf thymus had a molecular mass of 70kD and was identified to be the Tec protein-tyrosine kinase. This interaction between the PIP_3 analog beads and Tec could be efficiently inhibited by free PIP_3. Significantly higher concentrations of PI4, 5P_2, PI4P and IP_4 were required to compete this interaction. Studies with the various deletion mutants of Tec protein revealed that the binding site of PIP_3 was localized within the PH domain of Tec. Now we have demonstrated that our affinity gels are very useful biochemical tools to detect PIP_3 associated proteins. Moreover, we isolated a novel PIP_3 binding protein, Tee and Aktγ (which was also isolated by PIP_3-APBgel). These proteins have PH domains which turned out to be essential to interact with PIP_3. This PIP_3-PH interaction is likely to have a significance in the PI-3 kinase signal transdution pathway.

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This paper describes the relation between comfort of shorelines and psychological and physiological human responses deduced from the measurement results of electroencephalogram (EEG) and electrocardiogram (ECG), and questionnaire on comfort sensation and other related sensations. Regression analysis showed that the comfort sensation depends on aesthetics of landscape, noise, smell and temperature sensations under specific situations. It was found that the content ratio of some components of EEG frequency spectrum has a plausible relation to the comfort sensation, and shorelines are relatively comfortable in psychological and physiological senses.

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保護者と生徒の学校行事に関する交流に必要な情報の不足は,生徒が配布物等を保護者に提示していないこと,および教師と保護者の情報交流を行う機会が少ないことが原因として考えられた.そこで本研究は,Eメールなどのネットワーク機能を用いて教師と保護者間の情報交流を円滑にすることで,生徒と保護者間の情報交流を効果的に行うことを目的としたグループウェア(E-WEAR)を開発しその効果を検証した.検証実験の結果,教師から保護者への情報が効果的に提示されることで,保護者の学校行事についての関心が高まり,保護者と生徒の学校行事に関する交流改善の兆しが見られた.その反面,教師から保護者への情報が多くなったため,保護者から教師への質問等の情報提示が少なくなり,教師が保護者からの情報を入手しづらくなることもわかった.

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中山らは授業支援システムに個別対応機能を追加することで,学生の理解に応じた学習機会を提供し成績が向上することを明らかにした.しかし,システムを積極的に利用しない学生に対して,どのように意欲を向上させていくかが課題となった.そこで本研究では,学生のシステム利用に対する動機づけを高めるために,内発的および外発的動機づけに着目したシステムを開発し実践した.具体的には,授業の出席,小テスト,総合成績などの目標設定を授業前の段階で個別に行わせた後に,携帯電話を用いてそれらの結果を個別に評価教示を行い,結果に応じて目標設定を再確認させることで,システムを積極的に利用する動機づけを高めることができた.さらに,システムを用いた授業後に自分と他の学生との成績や出席などの達成率などを比較できることで,一斉授業における個人の位置づけが明確になり,他人との競争心が芽生え意欲も高まることも明らかになった.

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2020年の東京オリンピック・パラリンピックを控え，今後10年間での外国人観光客の増加が見込まれている．このような背景から，外国人にも利用しやすい観光情報の検索システムが望まれているが，言語の壁が課題となっている．言語の壁を解消するためには，システムの多言語化が一般的である．しかしながら，多言語化によって十分な数の言語を網羅することは難しく，真の意味で言語の壁を解消できない．そこで本稿では，一切の言語を用いずに観光情報を提供する検索システムを開発する．その特徴は，画像やピクトグラム，アラビア数字のみで検索インターフェイスを構成している点である．そして，被験者による評価実験によって，言語を用いずとも観光スポットの検索が可能なことを実証する．

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We developed a small coil and oscillator system for the hyperthermia of magnetic nanoparticles. The inner diameter and the length of the coil are 50 Φ and 60 mm, and we used them for the mice experiments. The frequency is 100 kHz, and the magnetic field is higher than 34.6 kA/m for the 5-Turn coil. Some experimental result is positive, and therefore we try to extend the system size for the human body in the same frequency and the same magnetic field intensity. Using the scale law in physics, and the coil is 500 Φ diameter, 600 mm length, and 5-Turn, but the magnetic field intensity and the frequency are the same as the present system. We design the instrument parameters. Fortunately, these design parameters are realistic to make a large device using the present electric parts in the market.

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The objectives of the study are to develop a system to measure the data of wind flow in both the horizontal and vertical directions utilizing inertial single photogrammetry, and to establish the methodology for three dimensional measurement on site of wind flow near the ground surface.
This system uses a one digital camera set on the ground, which photograph balloon released as a tracer, thereby three-dimensionally analyzing the balloon's path of particle.
The paper first describes the fabrication of an analytical method, followed by experiments carried out using the method. The experiments consisted of a provision and utility experiment. The provision experiment consisted of a measurement of the three-dimensional position of ball suspended in a laboratory with a single photograph of the ball being used. The utility experiments measured the paths of particles of wind flowing on the schoolyard.
The results of the experiments proved that the fabricated analytical method was effective.

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Nucleic acid therapeutics based on chemically synthesized oligonucleotides such as antisense oligonucleotide (ASO) or siRNA, are attracting attention as a new drug discovery. In the development of conventional nucleic acid therapeutics had been problems in in vivo stability and permeability to cell membranes. However, in recent years, they have been improved by modification of nucleic acid structure by several approaches such as phosphorothioate or bridged nucleic acid (BNA). Especially, 2’-O,4’-C-ethylene-bridged nucleic acid (ENA) is highly promising modified nucleic acid which has discovered from Daiichi-Sankyo. Herein, we have developed a highly efficient manufacturing method of ENA phosphoramidites as key intermediates for the synthesis of ENA containing oligonucleotides to increase the productivity and to reduce the manufacturing cost and lead time. The basic concept of the new synthetic route is “divergent synthesis” for the preparation of four types of monomers such as A, G, C and T. Namely, we set a common intermediate as downstream as possible to reduce the overall reaction steps. So the challenge was stereoselective glycosylation reactions without utilizing neighboring group participation. In addition, by changing the routes drastically and telescoping the multiple reaction steps, the productivity was significantly increased.

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