To investigate whether dantrolene (DAN), cardiac ryanodine receptor (RyR2) stabilizer, improves impaired diastolic function in an early pressure-overloaded hypertrophied heart, pressure-overload hypertrophy was induced by transverse aortic constriction (TAC) in mice. Wild-type (WT) mice were divided into four groups: sham-operated mice (Sham), sham-operated mice treated with DAN (DAN+Sham), TAC mice (TAC), and TAC mice treated with DAN (DAN+TAC). The mice were then followed up for 2 weeks. Left ventricular (LV) hypertrophy was induced in TAC, but not DAN+TAC mice, 2 weeks after TAC. There were no differences in LV fractional shortening among the four groups. Catheter tip micromanometer showed that the time constant of LV pressure decay, an index of diastolic function, was significantly prolonged in TAC but not in DAN+TAC mice. Diastolic function was significantly impaired in TAC, but not in DAN+TAC mice as determined by cell shortening and Ca2+ transients. An increase in diastolic Ca2+ leakage and a decrease in calmodulin (CaM) binding affinity to RyR2 were observed in TAC mice, while diastolic Ca2+ leakage improved in DAN+TAC mice. Thus, DAN prevented the progression of hypertrophy and improved the impairment of LV relaxation by inhibiting diastolic Ca2+ leakage through RyR2 and the dissociation of CaM from RyR2.

ダントロレン(DAN)はRyR2のN末端ドメインLeu601-Cys620に直接結合し、RyR2の4量体構造を安定化させることにより、RyR2からの拡張期Ca2+漏出を防ぐ。以前我々は、RyR2へのCaM高親和性KIマウス(V3599K)を用いて、横行大動脈縮窄(TAC)による圧過負荷誘発性心肥大マウスモデルにおいてRyR2からのCaM解離を抑制することで、Ca2+漏出を防ぎ、左室リモデリングを抑制することを報告した。そこで本研究では、横行大動脈縮窄（TAC）による圧負荷誘発性心肥大マウスモデルにおいてダントロレンの慢性投与がCaMとRyR2の結合親和性を遺伝的に強化した場合と同様の機序で左室リモデリングを抑制するかを調べた。横行大動脈縮窄（TAC）による圧負荷誘発性心肥大マウスモデルを作成した。野生型マウスを、Sham群、TAC群、TAC-DAN群(ダントロレン20mg/kg/day腹腔内投与)の3群に割り付けた。ShamまたはTAC手術から8週後の生存率、心機能および組織評価、単離心筋細胞を用いたCa2+ハンドリング、RyR2-CaM結合性の評価を行った。TAC-DAN群はTAC群と比較し、TAC手術から8週後の生存率は良好であった(TAC群 49% vs TAC-DAN群83%)。また、心エコーと心筋組織においては、TAC群で認めた左室リモデリングは、TAC-DAN群で抑制された。TAC手術から8週後の単離心筋細胞ではTAC群で拡張期Ca2+スパーク頻度の増加およびRyR2-CaM結合親和性の低下を認めたが、TAC-DAN群ではそれが抑制された。我々の研究はダントロレンの慢性投与によりRyR2を安定化させ、RyR2からのCaM解離を抑制することで、RyR2からの拡張期Ca2+漏出を防ぎ、左室リモデリングが抑制され、予後が改善することを示した。

現在の日本は少子高齢化・医療高度化を背景に、要介護者数の増加、医療費増加、人材不足、医療格差などの医療課題に直面している。近年、人工知能（ArtificialintelligenceAI）技術やシステム医学に基づいたデータ駆動型医療の登場によって、これら課題を解決できる可能性が広がった。筆者自身は呼吸器診療に携わる立場でもあることから、呼吸器診療を支援する以下3つの医療AI技術を開発した。1つ目の技術では、副作用ビッグデータ（JapaneseAdverseDrugEventReportJADER）に基づきベイズ推定を行うことで、AUC0.93の精度で副作用の原因薬を推定できた。呼吸器領域では薬剤性肺障害など重篤な副作用があるが、本技術の臨床応用によって、副作用による健康被害の最小化と副作用管理の効率化が期待できる。2つ目の技術では、喘息患者の臨床データ（年齢、BMI、血中好酸球数、呼気NO値、増悪回数）をもとに教師あり機械学習を行うことで、喘息患者の気流閉塞の急速進行1秒量低下）をAUC0.85の精度で予測できた。実用化によって、早期の治療介入が必要な喘息患者を同定でき、重症化を防ぐための先制治療につながる。3つ目の技術では、喘息質問票（AsthmaControlQuestionnaire-5:ACQ-5）のデータを用いて教師なし機械学習を行うことで、症状から喘息病態である気流閉塞、2型気道炎症、増悪リスクを推定できた。従来、治療選択のため病態評価には専門的検査が必要だが、本技術ではACQ-5に含まれる喘息症状の評価のみから、個々の喘息の病態に応じた治療選択（個別化治療）につなげることができる。本技術は、発展途上国、過疎地域、プライマリケアの現場など、医療環境が不十分な地域で、適切な喘息治療薬の選択を支援できる。ひいては、医療格差の是正につながる可能性が期待できる。本研究で開発したAI技術の実用化によって、臨床現場における副作用管理、先制医療、個別化治療を支援する。これによって、健康寿命の延伸、医療費抑制を目指す。同時に、開発したAI技術によって専門医療の一部を補完することで、医療従事者の業務負担軽減と、医療格差の是正均てん化につながることが期待できる。

細胞は熱ストレスなどのタンパク質毒性ストレスにさらされると、熱ショックタンパク質群（HSPs）を誘導することで適応する。この適応機構は熱ショック応答と呼ばれ、熱ショック転写因子HSF1によって主に転写レベルで制御される。活性化されたHSF1はHSP遺伝子プロモーターに存在する熱ショック応答配列（HSE）に結合し、メディエーターを含む転写開始前複合体を集積させることで転写を促進する。一般に、転写因子及びその調節因子は液―液相分離によってプロモーター上に凝縮体を形成すると考えられている。しかし、HSP遺伝子プロモーター上でも同様かどうかについては、凝縮体が微小であるために十分な解析ができていない。本研究では、ヒトHSP72プロモーター由来のHSEを多数連結したレポーター遺伝子をマウス細胞に導入した。このHSEレポーター遺伝子を持つ細胞に蛍光タンパク質mEGFPを融合したHSF1を発現させることで、熱ストレス条件下でHSF1凝縮体を可視化することに成功した。この人工的なHSF1凝縮体は部分的に液体様の性質を持つ、すなわち液―液相分離により形成されていた。また、大腸菌から精製したタンパク質を用いた実験から、HSF1の天然変性領域IDR)が相分離に寄与することも分かった。さらにこの実験系を用いて、HSF1凝縮体の形成が転写調節因子によって制御されるかを調べた。特に、熱ショック応答を促進するメディエーターの一つであるMED12に着目して解析したところ、MED12のIDRはHSF1凝縮体に集積すること、そしてMED12の発現抑制はHSF1の凝縮体形成を著しく抑制することが明らかとなった。本研究は、HSP72プロモーター上のHSF1凝縮体を解析する実験系を提示するとともに、それが転写調節因子によって制御されることを示唆する。

膵β細胞量の進行性の減少が糖尿病の発症・進展に関与する。糖尿病病態では、インスリン作用不足による高血糖に対する代償的なインスリン産生の増加や脂質異常のためにβ細胞において小胞体ストレスが亢進する。一方、セリン・スレオニンキナーゼGsk-3 はPI3/Akt により抑制され、Gsk-3 の活性制御障害がβ細胞不全と小胞体ストレス関連β細胞死に関連する。しかし、Gsk-3 を介した細胞障害の分子機構は十分に解明されていない。本研究では、Gsk-3 を介する小胞体ストレス応答調節と膵β細胞アポトーシス誘導の関連について検討を行った。方法：マウス単離膵ランゲルハンス氏島(ラ氏島)およびマウス膵β細胞株で薬理学的に小胞体ストレスを誘導した。Ins2 遺伝子に変異を持ち、変異インスリンの蓄積により小胞体ストレスが亢進しβ細胞死を来すAkita mouse 由来の膵β細胞株を遺伝的小胞体ストレスのモデルとして用いた。低分子化合物、あるいは酵素不活性型Gsk-3βの導入によりGsk-3 活性を阻害した。結果：小胞体ストレス下ではGsk-3 を抑制するAkt の活性が減弱しGsk-3 が活性化した。Gsk-3 はATF4 のSer214 リン酸化を介してATF4 とSCF-βTrCP の結合とそれに続くATF4 のユビキチン化、蛋白分解を促進する。したがって、Gsk-3 の抑制によりATF4 の分解速度が低下し、ATF4 蛋白質量が増加することが明らかになった。このとき、β細胞のアポトーシスが減弱することを確認した。この抗アポトーシス効果はdominant negative-ATF4 導入あるいはATF4 ノックダウンにより有意に減弱した。Gsk-3 抑制によるアポトーシス抑制のメカニズムについて、ATF4 の転写標的であるGADD34 および4E-BP1 の発現増強を介した全般的な蛋白翻訳の動態との関連が考えられた。さらに、Akita mouse 由来の膵β細胞株でもGsk-3 活性阻害によるアポトーシス抑制が確認され、これにはATF4 の発現増強と全般的な蛋白翻訳抑制が関連した。以上の結果より、インスリンシグナルとストレス応答のクロストークが明らかになり、Gsk-3/ATF4 経路が糖尿病におけるβ細胞保護の治療標的となる可能性が示唆された。

目的：アルコール使用障害（Alcohol use disorder: AUD）は治療後も再発率が高く再発を予測する患者の要因は確立されていない。AUDでは衝動制御障害、実行機能障害および意思決定障害が報告されているため、本研究ではそれらを用いてAUDの予後予測因子を前方視的に明らかにすることを目的とした。 方法：20歳から70歳までの入院中のAUD患者41名を対象とした。入院中に、①情動顔go/no-go課題（衝動制御課題）および言語流暢性課題（実行機能課題）中の脳血流活性化の指標である酸素化ヘモグロビン積分値を機能的近赤外分光法（functional nearinfrared spectroscopy: fNIRS）を用いて測定し、さらに②不確実な状況下でのリスク選好課題（意思決定）を行った。退院後6ヶ月の再発の有無を主要アウトカムとした。 結果：退院後、24名（58.5％）が断酒を継続し、17名（41.5％）が再飲酒した。断酒群に比べて再飲酒群では、①情動顔go/no go課題における右前頭側頭領域の活性化が有意に低下し、②意思決定課題では有意にリスク追及的であった。断酒群でのみ、右前頭側頭領域の活性と渇望尺度の間に負の相関が観察された。さらに、退院後6ヶ月の飲酒の有無を従属変数とし、年齢、AUD重症度、発症年齢、右前頭葉領域の酸素化ヘモグロビン積分値及び意思決定課題でのリスク選好の５つの独立変数を用いた2項ロジスティック回帰分析を行い、各独立因子の再発への影響を検討した結果、右前頭側頭領域の酸素化ヘモグロビン積分値が小さいほど（オッズ比＝0.161、p＝0.013）、またリスク追及傾向が強いほど（オッズ比＝7.04、p＝0.033）再発リスクが増加することが示された。 結論：右前頭側頭領域の情動刺激に対する脳血流活性化の低下と、リスク追及傾向が、AUDにおける退院6か月後の再発を予測し得る可能性が示された。

本論文は，申請者が山口大学大学院東アジア研究科在学中において進めてきた，遠隔教育支援環境における授業と学習活動の支援に関する研究をまとめたものである． 人口減少社会の到来により，特に地方において，適正規模での学校運営が難しい小規模の学校が増加傾向にある．小規模校では，きめ細やかな指導等が行える一方で，人間関係が固定化しがちであったり，多様な意見や考え方に触れることが少なくなったりなど，教育上の課題を抱えている．その解決策の１つとして，複数校の児童生徒が1つの学校に集まって合同授業が実施されているが，時間的・金銭的な問題などから実施回数が制限されるケースが多い．この合同授業を補う形で，日進月歩の勢いで進歩しているICT技術を活用した遠隔合同授業の取組みが期待され，教育実践が進められてきている． 一方，小学校や中学校だけでなく，大学などの高等教育機関においてもICTを活用した遠隔教育は進められてきている．さらに，新型コロナウィルス感染症のパンデミックを契機に，小学校・中学校・高校や高等教育機関だけでなく，塾など様々な場でオンライン授業あるいはオンライン学習といった遠隔教育の取り組みも行われてきている． しかしながら，オンライン授業や遠隔合同授業を実践する上では，環境整備面や授業実施面などで課題が存在する．特に，授業実施時における教員の作業負荷が非常に高いことが問題であり，オンライン授業や遠隔合同授業の特性や授業プロセスを踏まえた仕組みの構築や機能の開発が必要となる．さらに，オンライン授業や遠隔合同授業における学習者個人あるいはグループによる学習活動や，教員による教授活動や学習者グループの活動支援のプロセスを分析した上で，その状況に応じた支援手法を検討し，学習支援機能やその機能と連動した授業支援機能を遠隔教育支援ツール・アプリとして提供することが必要となる． そこで本研究では，高校・大学などにおけるオンライン授業や小学校・中学校の小規模校における遠隔合同授業といった遠隔教育を対象にして，校種やICT活用能力に応じた機能や画面に切り替えることができる設計思想を持った，課題解決的な学習が展開される際の学習者の学習活動と教員の教授活動を支援するための遠隔教育支援環境を設計して開発することを目的にする． 本論文では，本研究の目的を達成させるために，以下に示す5つの調査・研究・開発の成果がまとめられている． (1) 遠隔教育の支援環境に関する研究動向の調査 (2) 遠隔教育を支援する環境・機能についての整理と必要機能の提案 (3) 「クラス（学級）」と「個」をつなぐ遠隔教育支援環境「つながる授業アプリ」の開発と評価 (4) 「比べる」協働的思考活動支援機能の開発と評価 (5) グループ学習活動・対話状況確認支援機能とグループ活動状況管理機能の開発と評価 (1)では，遠隔教育に関する研究動向を調査した．これらの整理・分類などを踏まえ，遠隔教育における学習環境，学習支援機能，授業支援機能の研究に対する本研究の位置づけを行った． (2)では，遠隔教育をICTで支援する環境について説明した．さらに，2つのつながり（「クラス（学級）」と「個」）を保障する遠隔教育システムと協働学習支援システムに必要な機能を整理した． (3)では，遠隔教育システムと協働学習支援システムの両方の機能を併せ持つ遠隔教育支援環境「つながる授業アプリ」を設計・開発した．さらに，「つながる授業アプリ」のの有用性を評価し，基本機能を完成させた． (4)では，遠隔合同授業における小学生を対象として，より深い学びを実感できることを目的として，グループ活動時の思考に必要なプロセスを整理し，最も基本的な思考活動の1つである「比較思考」を協働的に進めることができる支援を「つながる授業アプリ」の拡張機能として実装した．「比べる」協働的思考活動支援機能は，「比べる」思考手順を１スライドずつ学習者間の協働的な思考手順として提示して，思考活動プロセスをガイドする仕組みである．さらに，開発した支援機能についてその有用性を評価した． (5)では，大学の遠隔教育を対象にして，グループ学習活動における学習者の対話内容の確認や振り返り，教員による見とりを支援する目的として，対話音声データ（バーバル情報）とノート記述データ（ノンバーバル情報）を活用した活動状況・対話状況の可視化機能を「つながる授業アプリ」の拡張機能として実装した．さらに，教員の見とり支援としてグループ活動状況管理機能も拡張機能として実装し，これらの機能の有用性を評価した． 以上により，オンライン授業が展開でき，学習者の個別学習やグループ学習の活動支援や教員の見とり支援が可能な「つながる授業アプリ」の開発・授業実践を通して，遠隔教育において必要な学習環境の要素機能，学習支援・授業支援の機能を確認することができた．

This dissertation focuses on the experiences of a group of Japanese university students who participated in a short-term study abroad program in the Philippines. While the main objective of the four-week sojourn was to improve the participants’ English language skills, I explored the effects of the trip holistically as a qualitative case study to examine the unique learning context of studying English in the Philippines, a relatively new phenomenon that has developed from the turn of the 21st century. The primary form of data I used was interview responses obtained from 14 focal participants among a larger cohort of 103 students who traveled together in the summer of 2018. The target students were mostly low to intermediate level (CEFR A2 to B1) before departure and returned at a marginally higher benchmark (CEFR B1 average) according to standardized testing scores. More importantly, most students did not have extensive international experience prior to the sojourn, and overall they expressed a more open stance to using English for communication after the trip. In this case and context, positive affective development occurred due to intensive one-on-one instruction with Filipino teachers who interacted with the Japanese students in a warm, friendly, and supportive manner. This learning situation is characteristically different from North American and other Western contexts typically associated with English learning, and with its relative ease of access geographically and financially, offers a practical alternative to Japanese students unable to study abroad otherwise. The results of this study indicate how Japanese learners of English adopt subtle changes in outlook through short-term study abroad programs in diversifying contexts. This research contributes significantly to the field of language learning in study abroad by documenting the perspectives of learners from Japan traveling within Asia. Study abroad itself is a relatively new area of inquiry which has focused predominantly on Western learners and contexts. Existing research on Japanese learners tends to concern privileged, advanced-level learners whose experiences may seem removed from the ordinary lives of students attending university in rural areas or those who do not consider themselves academically or socioeconomically exceptional. Furthermore, the amount of existing research on short-term study abroad is severely limited and does not thoroughly account for the experiences of Japanese learners of English in the Philippines, a study abroad destination which has gained substantial popularity but remains underrepresented. Accounting for the social, cultural, and ideological circumstances of learning in a non-native English speaking context in Asia allows for a more nuanced interpretation of how monolingual Japanese speakers first encounter English as an international language. I collected data in multiple forms to document the complexity of the case. As the participants’ English teacher and chaperone to the Philippines, I was immersed in the learning contexts in the students’ home country as well as abroad. Semi-structured interviews before and after the study abroad experience were conducted in the informants’ native language. Written questionnaires were administered to the larger cohort of students who traveled together to obtain a more general assessment of students’ impressions regarding the study abroad experience. Standardized test scores were accessed for reference. These multiple data sources were drawn on to illustrate the changes observed in the perspectives of the focal informants. While the learning experiences of each informant were unique, I identified common themes among the ways students collectively changed their attitudes and beliefs toward English and language learning through their participation in the short-term study abroad program. First, the learners in this study increased their self-confidence and motivation to learn English and overcame their fear, anxiety, and inhibition toward using English to varying degrees. Second, they expanded their interests in learning about other languages and cultures while becoming more aware of the boundaries of their own culture. Third, their perceived communicative ability in English improved, which they found was not the same as having to perform well on standardized English tests. Fourth, participants’ sense of success in improving their English language proficiency was less certain, reflecting their divergent test score gains on standardized exams. These reported changes in perspective were not lifechanging transformations of learners’ social identities, but their previously constructed views of language, culture, communication, and learning were evidently affected. The qualitative effects of study abroad experienced by the informants of this study cannot be assessed adequately with the language proficiency tests highly regarded in mainstream Japanese society. Language ideologies prevalent in the participants’ home and host contexts for learning need to be considered in order to explain why the changes occurred. The learners in this study initially had an additional affective barrier toward communication in intercultural contexts because they could not take advantage of the widespread use of English as a lingua franca without first making efforts to use English itself. Since they were used to monolingual discourses in Japan, the idea of using English as a lingua franca, not only as a “perfect” native language, had to be presented to them in a reallife situation. The study abroad experience nudged learners toward using English in ways that reflect the Global Englishes paradigm. These slight shifts in mindset are indicative of attitudinal changes gradually taking place within Japan and are not restricted to individuals who identify with international communities.

Not only taste but also flavor has a significant impact on the "deliciousness" of food as perceived by people. Flavor characteristics of food have a significant impact on its palatability and influence the qualitative value of the food itself. In this study, the molecular mechanisms of biosynthesis of flavor compounds derived from amino acids in soybean (Glycine max) and fatty acids in mushrooms were elucidated. In Chapter 1, I identified the characteristic aromatic properties of soybean due to sulfur-containing amino acids. Several soybean germplasms, such as Nishiyamahitashi 98-5 (NH) among local varieties in Nagano Prefecture, have an intense seaweed-like flavor after cooking because of their high seed S-methylmethionine (SMM) content. In this study, I compared the amounts of amino acids in the phloem sap, leaves, pods, and seeds between NH and the common soybean cultivar Fukuyutaka. This revealed a comparably higher SMM content alongside a higher free L-methionine (L-Met) content in NH seeds, suggesting that the SMM-hyperaccumulation phenotype of NH soybean was related to L-Met metabolism in seeds. To investigate the molecular mechanism behind SMM hyperaccumulation, I examined the phenotype-associated gene locus in NH plants. Analyses of the quantitative trait loci in segregated offspring of the cross between NH and the common soybean cultivar Williams 82 indicated that one locus on chromosome 10 explains 71.4% of SMM hyperaccumulation. Subsequent fine-mapping revealed that a transposon of about 6 kbp insertion into the intron of a gene, Glyma.10g172700, is associated with the SMM-hyperaccumulation phenotype. The Glyma.10g172700-encoded recombinant protein showed Met-γ-lyase (MGL) activity in vitro, and the transposon-insertion mutation in NH efficiently suppressed Glyma.10g172700 expression in developing seeds. Exogenous administration of L-Met to sections of developing soybean seeds resulted in transient increases in L-Met levels, followed by continuous increases in SMM concentrations, which was likely caused by L-Met methyltransferase activity in the seeds. Accordingly, I propose that the SMM-hyperaccumulation phenotype is caused by suppressed MGL expression in developing soybean seeds, resulting in transient accumulation of L-Met, which is converted into SMM to avoid the harmful effects caused by excess free L-Met. In Chapter 2, I studied the biosynthesis mechanism of 1-octen-3-ol, the main volatile component of mushrooms. 1-Octen-3-ol is a volatile oxylipin found ubiquitously in Basidiomycota and Ascomycota. As 1-octen-3-ol attracts mosquitoes and flies, its involvement in emitter–receiver ecological communication has been proposed. Although the biosynthetic pathway to form 1-octen-3-ol from linoleic acid through linoleic acid 10(S)-hydroperoxide has been proposed in mushrooms, the enzymes involved in this pathway have not been identified. I determined that the Coprinopsis cinerea dioxygenase 1 and 2 (CcDOX1 and CcDOX2) genes in the mushroom C. cinerea contains an N-terminal cyclooxygenase-like heme peroxidase domain and a C-terminal cytochrome P450-related domain. Through analysis of products formed from linoleic acid by the recombinant CcDOX1 and CcDOX2 proteins, I found that CcDOX1 preferentially catalyzes to form the 10(S)-hydroperoxide of linoleic acid (10S-HPODE), meanwhile CcDOX2 form the 8-hydroperoxide of linoleic acid. Moreover, disruption of Ccdox1 in C. cinerea (ΔCcdox1) mycelia suppressed 1-octen-3-ol synthesis. Administration of the 10S-HPODE to the microsome fraction prepared from mycelia resulted in the efficient production of 1-octen-3-ol. Together, these results indicate that CcDOX1 is essential for the biosynthesis of 1-octen-3-ol as the oxygenase that forms 10S-HPODE, followed by the cleavage enzyme. I studied physiological and ecological significance of 1-octen-3-ol of mushroom. ΔCcdox1 was less attractive to fruit fly larvae, while the feeding behavior of fungus gnats on ΔCcdox1 mycelia showed little difference from that on the mycelia of the wild-type strain. The proliferation of fungivorous nematodes on ΔCcdox1 mycelia was similar to or slightly worse than that on wild-type mycelia. Thus, 1-octen-3-ol seems to be an attractive compound for some animals that interact with mushrooms.

Indonesia has extreme risk of natural disasters because of its position at the confluence of four tectonic plates: the Asian Continent, the Australian Continent, the Indian Ocean, and the Pacific Ocean. The volcano eruption is one of the geological disasters that frequently occur in this country. Mount Merapi is Indonesia’s most active volcano and is famous worldwide. The evacuation crisis in 2010, the last major eruption, led to many fatalities for humans and cattle. Nowadays, the local government developed the "sister village" strategy for mitigation. That means cooperation within or between the local community has been constructed to provide shelter, logistics, and other disaster-related services. In this scenario, the meeting area and shelter have been coordinated. However, people's behavior has not been fully considered yet in the vulnerability assessment and government's contingency plan. On the other hand, evacuation issues in a volcanic disaster such as difficulty in expecting evacuation period, aging population, missed communication and risk perception, limited private vehicles in the community, and limited evacuation transport and supporters by the government need to be addressed for better mitigation. This situation led some people to walk to the meeting area, and low walking speeds by vulnerable persons may increase the risk and delay during an emergency. The objective of this study is to find the effectiveness of the evacuation process, especially for the vulnerable community in the Mount Merapi area. Especially, this study purposes to develop a “mutual assistance” model for vulnerable people in the affected regencies with the people’s behavior and vehicle ownership as a viewpoint. The first goal is an assessment of the mutual assistance strategy and social vulnerability index (SoVI) of pedestrian evacuation. I conducted the surveys and then analyzed the data using a multicriteria method to obtain the SoVI values for communities. The second goal is the development of the assembly model to support safer and faster evacuation for vulnerable people. The AnyLogic software was selected for model simulation using input parameters from field surveys. In conducting a survey, I measured the walking speed directly of the evacuation drills in four affected regencies. I also investigated the people’s behavior and eruption characteristics using an interview process with stakeholders and group discussions with local communities. After that, I used the multicriteria method and focused on two factors, social and age structure (young, vulnerable, and mutual assistance between them), and risk perception (work, rain, night, alert, and evacuation map). The index reflects the distribution of actual walking speed, mutual assistance, and the government's plan. The result showed that mutual assistance groups have a higher walking speed than vulnerable people but lower than young people. Mutual assistance coordination is crucial to support the vulnerable in shorter evacuation times. The social and age structure of the social vulnerability index has a stronger risk influence than the perception factor in the evacuation process. The successful evacuation of vulnerable people during emergencies is a significant challenge. In this study, a mutual assistance strategy is proposed to support vulnerable people by evacuating them with young people. This strategy was simulated using AnyLogic software with the agent-based model concept. Pedestrians and vehicles played the roles of significant agents in this experiment. Evacuation departure rate, actual walking speed, group size, route, and coordination were crucial agent parameters. Residents’ attitudes, distribution of each agent, and actual walking speed were obtained from surveys. Then, I developed three scenarios and three models for the evacuation process. Scenarios considered traffic conditions of evacuation routes and models represented behavior approach. The results revealed that this mutual assistance model is effective for the rapid evacuation and risk reduction of vulnerable communities where successful evacuation rates have improved. As for mutual assistance behavior, Model 3, where young people are matched with vulnerable people in advance, has shown better results than Model 2. Additionally, Scenario C, where pedestrians have separate lanes from vehicles during the evacuation process, has resulted in more number of vulnerable people reaching the shelter than Scenario B in Model 3. The highest arrival rate was obtained by the combination of scenario C and Model 3. These findings are a novelty in the volcano context and reflect all categories of vulnerable behavior involving the elderly, disabled, children, and pregnant mothers. The model will benefit disaster management studies and authorities’ policies for sustainable evacuation planning and aging population mitigation.

Population growth drives the demand for energy, which is the most pressing human need today. It puts pressure on other related sectors and increases wastewater production, which is a big problem in some countries that is inaccessible to available wastewater treatment facilities. Concerning the SDGs 2030 target, which mentions integrated sectors to deal with environmental issues, energy and water as a part of the water-energy-food nexus have a high linkage to build substantial economic and ecological benefits. Therefore, they have become the core attention of the world at this moment. To deal with the problem solving mentioned above, nowadays, an alternative energy converter integrated wastewater treatment has been massively developed to achieve green label production of products. Many countries, favoured by their scientists and practitioners, compete to find technology that is a user-friendly, eco-friendly, back-to-nature concept, inexpensive and can be accepted in any society stratifications. However, there is an available standalone converter technology known as conventional technology, which is a disintegrated system with no added value. This challenge opens an opportunity to develop a fully integrated system with any advantages. One of the promising technologies needed for solving the environmental problem and simultaneously producing other benefits for human living is a part of the bioelectrochemistry system (BES), which is microbial fuel cell (MFC). It could be easily assisted with the available conventional wastewater treatment, and it gives more benefits not only in energy production but also for remediating the environment through the superior biocatalyst, named electroactive bacteria (EAB), which has the availability to reduce organic and inorganic matter and generating electricity. However, factors affecting MFC have been a drawback in their field application that must be concerned extensively. Therefore, this study accommodates to investigation more in order to get an optimum condition in operation so that the technology could be widely used properly on the full scale. The disadvantages of the air–cathode single-chamber microbial fuel cell (AC-SCMFC) performance can be caused by numerous factors, and retention time (RT) is one such factor. It is difficult to conclude the ideal RT run for the specific tests under the same conditions. To determine the optimum RT for various types of microbial fuel cell (MFC), an AC-SCMFC batch-mode reactor was carried out by comparing different types and concentrations of substrates based on the main parameters of organic removal and power generation. The AC-SCMFC reactor was designed for the effective working volume of 500 mL and operated for 52 d in batch mode with factors being significantly correlated with the performance of the MFC reactor, which were two different substrates, sucrose and acetate, and three different chemical oxygen demand (COD) levels of 400; 1000, and 2500 mg/L (low, medium, and high, respectively) equipped with two graphene nanoplatelets (GNPs)-based electrodes connected to 100 Ω resistance and plugged onto a ii data logger. The results of this study indicated a significant pattern at the medium level, at which the optimum RT of sucrose was achieved at 24 h and that of acetate at 48 h. In comparison, the performances pattern at low and high levels of both substrates was insignificant to determine the optimum RT. For further application, the recommended RT for both substrates at any concentration is 24 h due to high overall performance, and the optimum RT established in this study could be applied to all types of MFC research, particularly in oxidizable or biodegradable organic ranges, which ensures high performance. One of the important factors in enhancing the performance of microbial fuel cells (MFCs) is reactor design and configuration. Therefore, this study was conducted to evaluate the regressors and their operating parameters affecting the double anode chamber–designed dual-chamber microbial fuel cell (DAC-DCMFC) performance. Its primary design consists of two anode chamber compartments equipped with a separator and cathode chamber. The DAC-DCMFCs were parallelly operated over 8 days (60 days after the acclimation period). They were intermittently pump-fed with the different organic loading rates (OLRs), using chemically enriched sucrose as artificial wastewater. The applied OLRs were adjusted at low, medium, and high ranges from 0.4 kg.m-3.d-1 to 2.5 kg.m-3.d-1. The reactor types were type 1 and type 2 with different cathode materials. The pH, temperature, oxidation-reduction potential (ORP), optical density 600 (OD600), chemical oxygen demand (COD), and total organic carbon (TOC) were measured, using standard analytical instruments. In general, the power production achieved a maximum of 866 ± 44 mW/m2, with a volumetric power density of 5.15 ± 0.26 W/m3 and coulombic efficiency of 84%. Two-stage COD and TOC removal at medium OLR achieved a range of 60–80%. Medium OLR is the recommended level to enhance power production and organic removal in DAC-DCMFC. The separated anode chambers into two parts in a dual anode chamber microbial fuel cell adjusted by various organic loadings expressed a preferable comprehension of the integrated MFCs for wastewater treatment. With respect to both studies, RT influences the design and configuration of MFCs, particularly in this regard, modified anode compartment of DCMFCs adapted to the range of oxidizable or biodegradable organics and reactor components towards control and dependent variables provide the simultaneous performance of DCMFCs in organic removal and power generation. In addition, DAC-DCMFC offers an opportunity to achieve optimal conditions in concurrent MFC-assisted wastewater treatment. Therefore, this study is one step closer to understanding the operating conditions comprehensively, which are the dominant factors affecting performance.

Access to clean water has been crucial global problem, especially with climate change, increasing population, and industrial activities. As one of Malaysia’s leading economic activities, the Oil and Gas Industry generates a massive amount of wastewater called Produced Water (PW). Dissolved organics in produced water, such as organic acids and phenolic compounds, are concerning due to the possibility that they can be toxic, non-biodegradable, and have bioaccumulation properties. Conventional treatments such as adsorption, incineration, and biological treatment seem to have difficulties treating these dilute but toxic components in an economical and environmentally friendly manner. Regulations on wastewater management has also been stricter around the globe. Therefore, there is a need on a new water treatment method to treat the diluted organics in a large volume of wastewater. Membrane technology has been of interest in the water treatment technologies’ industrial and research scenes. It offers simpler configuration and maintenance. However, the application is limited by the reduction of performance over time due to fouling phenomena. Photocatalyst offer an effective method to decompose organics in an environmentally friendly manner. This study researched on photocatalytic removal of diluted organic in water and potential of biofouling reduction by deposition of AgTiO2 coating on membrane surface. In Chapter 1: Introduction, the research background and purpose of this research were discussed. At the end of this chapter, the thesis framework was shown. In Chapter 2: Preparation and characterization of TiO2 and AgTiO2 coatings; the method to prepare AgTiO2 coatings on membrane support were explained. The prepared membranes were characterized with XPS, SEM, TEM, and ICP analysis to understand the prepared coatings. Results shows that the concentration of silver deposited on the membrane can be control by the concentration of silver in the precursor (silver acetate solution) used during the photochemical deposition step. Via XPS, it was found that the state of silver prepared through this method is oxide state. In Chapter 3: Removal of dissolved organic pollutants in water by photooxidation, the photocatalytic performance of prepared membranes was studied. Decomposition of diluted formic acid was performed under UV-light, and the concentration was evaluated using UVspectrophotometer. AgTiO2 membranes show better photocatalytic activity then TiO2 membrane. The concentration of silver on the membrane was found to influence its photocatalytic performance. In relation to PW application which commonly contain high salts, influence of salt types; NaCl, MgSO4, MgCl2 and K2SO4 and concentration were studied. All salts were found to inhibit the membranes’ photocatalytic performance. In Chapter 4: Antibacterial activity of AgTiO2 membranes, the antibacterial activity towards E. coli by prepared AgTiO2 membranes were investigated. Silver dissolution from membrane was found to be significantly increased in the presence of NaCl as compared to only water. Comparing membrane with lower Ag deposition, and around 20 times higher deposition, the silver dissolution from these membranes reached almost the same value after some time. However, as the amount of silver deposited on the membrane was higher, the antibacterial performance show around four times higher than the lower silver membrane. Based on other tests performed, it was concluded that there are potential of contribution from the silver oxide deposited on the membrane surface on the antibacterial activity of the AgTiO2 membranes In Chapter 5: Antibacterial activity in filtration system, prepared AgTiO2 membrane was used to filter E. coli suspension in water. E. coli growth was found to be inhibited by short contact with silver on the coated membrane. Finally, Chapter 6: Conclusion, the thesis was summarized, and future works were proposed.