ヒト血清アミロイドA の凝集および阻害活性のin vitro 評価、お よびPerilla frutescence var. crispa とSanguisorba tenuijfolia var. alba によるマウスAA アミロイドーシス抑制効果の検証

室蘭工業大学Muroran Institute of Technology博士（工学）血清アミロイド A (SAA) は、アミロイドーシスの研究中に発見された最も重要なアミロ イド前駆体タンパク質の 1 つであるが、その凝集メカニズムはまだ十分に解明されていな い。SAA の凝集は AA アミロイドーシスの発症における重要なステップであるため、アミ ロイド阻害剤はその発症を研究するためのツールとして使用できる。以前、当研究室では量 子ドット (QD) 蛍光イメージング技術を基にアミロイド β (Aβ) 凝集阻害剤をスクリー ニングする微量ハイスループットスクリーニング（MSHTS） システムを報告した。本研究で は、リン酸緩衝生理食塩水中のヒト SAA (hSAA) の凝集を報告し、蛍光顕微鏡と共焦点顕 微鏡を使用して QD による hSAA 凝集の可視化に成功した。2 次元および3 次元画像解析に より、40 μM のhSAA で大量の凝集が観察され、これがin vitro における凝集の最適濃度 であることが確認された。この発見の正確さは、チオフラビン T アッセイによって検証さ れた。透過型電子顕微鏡の結果から、QD が hSAA 凝集に均一に結合することが示された。 hSAA 凝集阻害活性はロスマリン酸 (RA) によっても評価された。その結果は、Aβ 凝集に 対して高い阻害活性を示す化合物である RA が、40 μM hSAA に対しても高い阻害活性を示 した。これらの結果は、MSHTS システムが hSAA 凝集体の可視化と高活性阻害剤のスクリ ーニングに効果的なツールであることを示した。 そこで、MSHTS システムを用いて、Perilla frutescens var. crispa およびSanguisorba tenuijfolia var. alba 抽出物のmSAA 凝集に対する阻害活性を評価した。その結果、両抽 出物はAβ 凝集に対して高い阻害活性を示し、50 μM のmSAA 凝集に対しても高い阻害活性 を示した。また、1%のPerilla frutescens var. crispa およびSanguisorba tenuijfolia var. alba 抽出物をマウスに投与し、臓器へのSAA 沈着を評価したところ、両抽出物を与え たマウスではコントロールに比べて臓器のアミロイド沈着量が低下した。これらの結果は、 Perilla frutescens var. crispa およびSanguisorba tenuijfolia var. alba の食餌摂取 がSAA 凝集に対する阻害効果を持ち、臓器におけるSAA 沈着を抑制することを示唆した。 結論として、これらの抽出物はAA アミロイドーシスの予防において有望な可能性を持つが、 その効果と作用機序をより深く理解するためには、さらなる臨床研究が必要である。Serum amyloid A (SAA) is one of the most important precursor amyloid proteins discovered during the study of amyloidosis, but its underlying aggregation mechanism has not yet been well elucidated. Since SAA aggregation is a key step in the pathogenesis of AA amyloidosis, amyloid inhibitors can be used as a tool to study its pathogenesis. A novel microliterscale high-throughput screening (MSHTS) system for screening amyloid β (Aβ) aggregation inhibitors was previously reported, utilizing quantum dot (QD) fluorescence imaging technology. In this study, I reported the aggregation of human SAA (hSAA) in phosphate-buffered saline, in which I successfully visualized hSAA aggregation by QD using fluorescence microscopy and confocal microscopy. Two-dimensional (2D) and three-dimensional (3D) image analyses revealed large amount of aggregation at 40 μM hSAA, identified as the optimal concentration for aggregation in vitro. The accuracy of this finding was verified by a Thioflavin T (ThT) assay. The transmission electron microscopy (TEM) results showed that QD was uniformly bound to hSAA aggregation. hSAA aggregation inhibitory activity was also evaluated by rosmarinic acid (RA). The results showed that RA, which is a compound with high inhibitory activity against Aβ aggregation, also exhibited high inhibitory activity against 40 μM hSAA. These results indicate that the MSHTS system is an effective tool for visualizing hSAA aggregation and for screening highly active inhibitors. Therefore, I evaluated the inhibitory activity of Perilla frutescens var. crispa and Sanguisorba tenuijfolia var. alba extracts on mSAA aggregation using the MSHTS system. The results showed that Perilla frutescens var. crispa and Sanguisorba tenuijfolia var. alba extracts had high inhibitory activity against Aβ aggregation and also showed high inhibitory activity against 50 μM mSAA aggregation. I evaluated the deposition of SAA in the organs of mice by feeding them 1% Perilla frutescens var. crispa and Sanguisorba tenuijfolia var. alba extracts. The amount of amyloid deposition in the organs of mice fed with both extracts was lower than that of the control group. These results indicate that dietary intake of Perilla frutescens var. crispa and Sanguisorba tenuijfolia var. alba extracts inhibited the deposition of SAA in organs. In conclusion, the potential application of the Perilla frutescens var. crispa and Sanguisorba tenuijfolia var. alba in the prevention of AA amyloidosis are promising, but further clinical studies are needed to fully understand their benefits and mechanisms of action.doctoral thesi

寒冷地の路床・路盤への軽量材の高度利用に関する研究

室蘭工業大学Muroran Institute of Technology博士（工学）本研究は，寒冷地におけるアスファルト舗装道路の補修性や耐久性の向上を目指し，地盤条件や気象条件に適した路床と路盤の改良を提案するものである．本研究では，リサイクル材を原料とした軽量盛土材として、下水汚泥と膨張性頁岩を原料にした人工軽量盛土材（軽量材KG）と，廃ガラスを原料としたガラス発泡軽量材（軽量材SS）の2種類を選定した．軽量材KGは路盤への適用性，軽量材SSは路床への適用性を主目的としている．これらの材料を用いて土質試験や凍上試験，繰返し載荷試験，熱的特性試験を実施した．また，寒冷地における切込砕石の上層路盤への適用性を検討するため，粒度調整した砕石を用いてCBR試験と凍上試験を行った．論文の構成は以下の通りである． 第1章では，本論文の背景と研究目的を述べるとともに，論文全体の構成を示した． 第2章では，本研究で使用するリサイクル軽量盛土材の諸元に加え，先行研究で得た知見や問題点を整理するとともに，路盤材の寒冷地利用における既往研究として，粒度調整砕石の上層路盤への適用性や下層路盤における凍結融解履歴に関する研究事例を整理した． 第3章では，軽量材KGの性状確認のための土質試験や凍上試験に加え，珪砂を混合して簡易的に粒度調整を行った3試料においてCBR試験，2種類の拘束圧及び繰返し載荷の有無の条件で三軸試験を実施し強度・変形特性を検討し，剛性と軽量性を併せもつ適正な粒度を提案した． 第4章では，軽量材SSの性状確認のための土質試験やCBR試験および凍上試験に加え，熱的定数を調べて粒子内に多くの間隙が存在することの効果により一般的な砕石と比較して優位な熱的性質であることを示した．さらに凍結深さの抑制効果を熱伝導解析によって明らかにした． 第5章では，寒冷地における粒度調整砕石の最適粒度を検討するため、耐凍上性と支持力を両立する粒度の検討を目的とし品質規格の範囲内で粒度調整した砕石を用いてCBRと凍上試験を実施した．その凍上試験結果，供試体の上部に未凍結部からの水蒸気移動が原因と疑われるアイスレンズが発生する特異な状態を示した．そこで，砕石に対する凍上性判定の課題整理を目的に種々の条件で凍上試験を実施し，供試体上部の密閉度や下部の防湿性が凍上量に与える影響を明らかにすることで水蒸気移動による凍上を裏付けた． 第6章は結論として，本研究の成果の主体をなす第3～4章の内容を総括し，本研究で目指したリサイクル軽量盛土材の路盤または路床への高度利用の適用性を示すとともに第5章で検討した粒度調整した砕石における水蒸気に起因した疑似凍上発生のメカニズムを示し，最後に今後の課題について述べた． 本研究は，寒冷地におけるアスファルト舗装道路の維持管理や耐久性の向上を目指した取り組みに位置づけられ，一連の三軸試験，CBR試験，凍上試験を系統的に実施し，提案する新たな路盤材には，粒子内に多くの間隙が存在することの効果により一般的な砕石と比較して優位な熱的性質であることを明らかにするとともに，凍結深さの抑制効果を熱伝導解析によって明らかにしており，本研究による成果は，寒冷地の既設道路における路床・路盤材の改良に関する研究に対して，社会的に大いに寄与するものであると考えられる．This study focuses on improving the repairability and durability of asphalt pavements in cold regions by adapting the subgrade and subbase course to the soil and weather conditions. Two types of recycled lightweight embankment materials were selected: KG lightweight material (made from sewage sludge and expansive shale) for the subgrade and SS lightweight material (made from waste glass) for the subgrade. Various tests, including soil tests, frost heave tests, cyclic loading tests, and thermal property tests, were performed on these materials. In addition, CBR and frost heave tests were performed on graded crushed stone to evaluate its suitability for upper base course in cold regions. The thesis is structured as follows: 1） Introduction: Background, objectives and structure of the thesis; 2）Literature Review: Previous studies on base course materials in cold regions, focusing on lightweight material and graded crushed stone; 3） Lightweight material KG: Soil tests, frost heave tests, CBR tests with silica sand, and triaxial tests to propose optimal grading; 4） Lightweight material SS: Soil tests, CBR tests, frost heave tests, and thermal property measurements to highlight superior thermal properties. Graded crushed stone: Optimal grading to balance frost heave resistance and bearing capacity, with tests showing ice lenses due to water vapor movement; 5） CBR and freeze-up tests were conducted to determine the optimal grain size of graded crushed stone in cold regions. The tests aimed to find a grain size that balances freeze-up resistance and bearing capacity. Results showed ice lenses forming in the upper part of the specimen, due to water vapor migration from the unfrozen part. Various conditions were tested to understand the effects of sealing the upper part and damp-proofing the lower part on freezing, confirming that water vapor movement causes freezing; 6) This chapter summarizes the main findings from Chapters 3 and 4, demonstrating the applicability of recycled lightweight embankment materials for advanced use in base and subgrades. It also explains the mechanism of pseudo-freezing caused by water vapor in graded crushed stone, as investigated in Chapter 6, and discusses future challenges. This study is positioned as an effort to improve the maintenance and durability of asphalt paved roads in cold climates region. In this study, a series of triaxial tests, CBR tests, and frost heaving test were conducted systematically. The proposed new roadbed and subgrade materials were shown to have a large number of voids within the particles, and the effect of this on the thermal properties was found to be superior to that of ordinary crushed stone. The effect of the freezing depth suppression is also clarified by heat conduction analysis. The results of this study are expected to make a significant contribution to research on the improvement of roadbed and subgrade materials on existing roads in cold regions.doctoral thesi

Memoirs of the Muroran Institute of Technology No. 74

個々の収録アイテムdepartmental bulletin pape

Anomalous chirality dependence of strain energy in gold nanotubes

A recent experiment reports a creation of goldene, which is two-dimensional gold with hexagonal structure. By rolling up the goldene, gold nanotubes (GNT) should exist, but their structural and electronic properties are not understood well. Based on first-principles calculations, we demonstrate a breakdown of inverse square law, wherein the strain energy stored in a GNT decreases with the inverse square of the GNT radius. This is due to the enhanced strain energy in specific GNTs. The specific chiralities are identified by imposing the Bloch and geometric boundary conditions to the electronic structure of goldene having a hexagonal shape of Fermi surface. We also confirm that the electronic states on the Fermi surface exhibit in-plane character. These factors result in an increase in the strain energy.journal articl

高強度コンクリートの圧縮強度および収縮特性に及ぼすフライアッ シュ混和およびその減水作用の影響

高強度コンクリートの圧縮強度および収縮特性に及ぼすフライアッシュの混和およびその減水作用の影響を明らかにするために，圧縮強度試験および収縮試験を実施し，単位水量を一定にしたものと減少させたものとの比較を行った。水結合材比は30%一定，フライアッシュの置換率は0%，10%，20%，30%と変化させた。その結果，フライアッシュ置換率が増加するほど圧縮強度および自己収縮は減少，乾燥収縮は増加 すること，単位水量を減少させることで，圧縮強度および自己収縮は若干増加，乾燥収縮は減少することがわかった。journal articl

Estimation of floc condition in a dewatering process by image analysis using machine learning

Dewatering is a crucial process in sludge treatment plants, and appropriate mixing of polymer and sludge is an important factor in achieving efficient dewatering. This study focused on the condition of flocs produced by mixing sludge and polymer, and estimated the floc condition through visual analysis of images. In this study, the estimation of floc condition was assumed to be a classification problem of mixer speed, and validation was conducted to classify the appropriate speed based on the images. The proposed methodology involved the development of a machine learning model characterized by high accuracy and transparency. This model was formulated using two features extracted from the images, i.e., the gaps between flocs and their texture, which are the parameters used by human operators to estimate floc condition. Explainable Boosting Machine was used as the machine learning model, which allows interpretation of the model’s contents and can be applied easily. The classification accuracy of this model was validated using both interpolated and extrapolated data, yielding accuracies exceeding 95% in both scenarios. Furthermore, comparative analysis was performed between the proposed transparent box model and a conventional Convolutional Neural Network (CNN) model. Despite its transparent box nature, the proposed approach demonstrated a comparable level of accuracy to the CNN model in this comparative study.journal articl

Using PAC analysis to decipher an instructor's own impressions of the teacher license renewal courses

From 2009 to 2022, a teacher license renewal system was implemented in Japan. Teachers were required to take the courses once every 10 years. Previous studies have revealed that teachers who took the courses positively evaluated the courses, but also expressed dissatisfaction with the heavy burden of taking the courses. However, there has been little discussion of the impressions of university teachers who lecture on the courses. In this paper, we used PAC analysis to listen to a university teacher’s impressions of the renewal courses and obtain advice from other university teachers to make the interpretation more multifaceted. University teachers made efforts to improve the renewal courses, but because participation in the courses were compulsory, it was difficult for their efforts to be rewarded. It has emerged that the new training system should ensure the autonomy of teachers and the autonomy of university teachers.departmental bulletin pape

High-Pressure Synthesis, Crystal Structures, and Hydrogenation Properties of MgYNi and (Mg,Y)2Ni Compounds

This study presents two new structures of compounds in the Mg−Y−Ni ternary system, MgYNi with a hexagonal ZrNiAl-type structure and Mg2-xYxNi with an orthorhombic Mg2Cu-type structure, both obtained through a high-pressure synthesis technique at GPa-order pressures. MgYNi with the ZrNiAl-type structure underwent a phase transformation into an orthorhombic MoAlB-type structure at 622 K in an Ar atmosphere via an exothermic reaction. Additionally, 2 MgYNi with the ZrNiAl-type structure exhibited hydrogen absorption at 313 K under 5 MPa H2 and formed MgYNiH∼4.7 with the ZrNiAl-type structure, resulting in volume expansion of approximately 24.7%. Mg2-xYxNi with the Mg2Cu-type structure was obtained at 0.12 < x < 0.26. Hydrogenation of Mg2-xYxNi with the Mg2Cu-type structure at 598 K and 8 MPa resulted in decomposition into monoclinic and orthorhombic phases of Mg2NiH4 along with YH3 and Ni. Hydrogen desorption temperature of the hydrogenated Mg2-xYxNi was approximately 50 K lower than that of Mg2Ni after hydrogenation.journal articl

反復有限要素法とCMA-ESを用いた非線形光デバイスの最適設計

光Kerr 効果を利用した光デバイスは，高速に応答する光スイッチが実現可能であり，線形光デバイ スでの実現が難しい全光論理ゲートや光リミッタなどの実現が可能である．しかしながら，非線形問題を直接解 くことは一般に容易ではない．そのため，適当な初期解を用いた反復解法がよく用いられるが，解の収束性に注意 する必要がある．本研究では，伝搬解析手法として用いる反復有限要素法の収束性の改善を行い，構造表現手法 として関数展開法，最適化手法として共分散行列適応進化戦略(CMA-ES) を用いた非線形光デバイスの最適設計 について検討を行っている．最適設計例として光スイッチと光NAND ゲートをとりあげ本手法の有用性を示す．journal articl

Improvement and Future Issues in “Basics of Economy” and “Economy Today”

This report discusses improvements and issues in the lectures of the liberal arts courses " Basics of Economy" and "Economy Today". Improvements in "Basics of Economy" include the promotion of communication with students and the implementation of group discussions among students. Problems with "Basics of Economy" include issues that occur in group discussions, the adverse effects of large classes, time constraints, and fairness among classes. Improvements of "Economy Today" include teachers' understanding of students' level of understanding due to the face-to-face teaching, renewal of lecture contents, and inviting new outside lecturers. The issue unique to "Economy Today" is the selection and appointment of appropriate external lecturers.departmental bulletin pape