回顧與前瞻 (Personal Reflections)

分五部分，第一部分「2001年國科會邀請撰述研究回顧」，第二部分「2012年國防醫學院生化科所退休專題演講」及相片、留言，第三部分「國際酒癮生物醫學研究學會2012年通訊」，第四部分「2014年慈濟大學醫學科學研究所研究典範專題演講」，第五部分「2015年自國際酒癮學術期刊ACER領域編輯退休通信」，第六部分「2017年紀毓周發表論文受邀毒理及製藥科技國際會議演講」(另含該年新增7份，共9份，生物能源、疫苗科技、基因體學、胃腸醫學、代謝體學國際會議邀請演講函)。

(1)「2001年國科會邀請撰述研究回顧」

Life Sci. News Lett. NSC 15:1-8, 2001

人類酒精代謝酶系統的酶學、分子遺傳學和臨床醫學研究之回顧

國防醫學院生化學科 尹士俊

一、緒言

　　經濟進步，社會工業化，國人的飲酒觀念和習慣受到西方文化影響。自1950年代至1980年代，國內酒類包括啤酒的年消耗總量增加達10倍之多⁽¹⁾。同一時期，不論漢人或原住民的酒精依賴盛行率也分別增高約10倍⁽²⁾。國內酒消耗量和酒癮盛行率同時增高的趨勢持續迄今^(1,2)。近年的流行病學研究顯示，台灣男性漢人的酒精依賴終身盛行率，僅為男性原住民盛行率的 8%⁽³⁾，和美國及加拿大男性白人族群比較，則為其17%⁽⁴⁾。所以漢人酒癮盛行率顯著較台灣原住民和西方白人為低，其間有社會、經濟及文化因素參與，亦受到遺傳因子影響。過去20年來，我一直從事酒精研究，探討保護東方人不易罹患酒癮的生物因子。我們長程的實驗假說是，人類酒精代謝酶系統對偶基因 (allele) 發生變異，造成所決定的對偶同功酶 (allozyme) 的動力學性質不同，因此影響乙醇及其代謝產物乙醛在人體的藥物動力學 (pharmacokinetics) 及藥物效力學 (pharmacodynamics)，進而影響飲酒行為、器官組織傷害和酒癮的發生。

二、人類酒精代謝酶系統：基因、酶性質與代謝

　　酒精在人體內分解，90-95% 以上經由氧化途徑，包括醇脫氫酶 (alcohol dehydrogenase，簡稱ADH)、細胞色素 (cytochrome P450s，尤其是P450IIE1)、過氧化酶 (catalase) 和醛脫氫酶 (aldehyde dehydrogenase，簡稱ALDH)，其中以醇脫氫酶和醛脫氫酶途徑為主^(5-8)。ADH和ALDH均呈複雜的酶族 (family)，其對偶同功酶具種族差異。

　　人類醇脫氫酶族有6個基因，位於4號染色體q22-24區，依酶的結構和催化特性區分為四類 (class)^(6,7)。第一類屬低Km (乙醇的Km值＜5 mM)，包括 α-ADH、β-ADH、γ-ADH；第二類屬高Km，有 π-ADH (34 mM)；第三類 χ-ADH (＞3 M)，因其 Km 值過高而無法有效參與乙醇在體內的代謝；第四類 µ-ADH亦屬高Km (29 mM)。ADH族中，不同類彼此間的胺基酸序列相同性達60%，同一類的同功酶則超過90%。第一類的 β-ADH和 γ-ADH有對偶同功酶，其基因表現序列中1個 (β-ADH) 或2個 (γ-ADH) 核酶酸不同，分別造成1或2個胺基酸的差異。 β₁-ADH和 β₂-ADH分別主要存在於西方白人和東方中國、日本、韓國人族群，β₃-ADH僅在非洲黑人族群發現。東方人和黑人族群以 γ₁-ADH為主要的對偶同功酶，西方白人族群中γ₁-ADH和γ₂-ADH的分佈頻數相近。β₂-ADH和β₃-ADH對乙醇氧化的最大催化速度 (Vmax) 分別是β₁-ADH的44倍和35倍，γ₁-ADH是γ₂-ADH的2.5倍，所以他們均屬高Vmax對偶同功酶。

我們過去最先鑑定並純化東方人肝中4種含β₂ 次單元的同功酶，發現同雙元分子β₂β₂的高Vmax歸因於其催化反應的限速步驟在E-NADH的解離，而與輔酶的焦磷酸基結合的47位置在β₁β₁的強鹼精胺酸被β₂β₂的弱鹼組織胺酸所取代的緣故^(9-11)。我們第一個報告從人胃黏膜發現一新類的ADH，命名為 μ-ADH⁽¹²⁾。根據人類ADH族成員對乙醇的催化機制及動力學常數特性，我們對其分類從代謝角度作一功能性詮釋⁽⁷⁾。為避免文獻不同物種ADH族成員的名稱不一致造成混淆，也便於作物種間ADH結構及功能比對，1999年筆者和八位國際醇脫氫酶領域知名學者推薦一個適用於所有脊椎動物ADH族的新命名系統⁽¹³⁾。

　　人類醛脫氫酶巨族 (superfamily) 至少有12個基因，其間的胺基酸序列相同性約在15% 和80% 之間，他們的基質專一性差異甚大。乙醛作為基質的ALDH1 (Km值33 μM) 和ALDH2 (0.20 μM) 屬低Km類，ALDH3 (75 mM) 則屬高Km 類⁽¹⁴⁾。東方人族群約50% 具ALDH2*2變異型對偶基因，它位於12號染色體q24的位置，在表現序列12有一點突變，造成487位置麩胺酸換成離胺酸，導致酶失去活性⁽⁸⁾。ALDH2*2 在人類其他族群尚未發現，所以是東方人特有的對偶基因。我們最先報告在人胃黏膜表現的ALDH3的基質專一性迥異於ALDH1和ALDH2^(15,16)，所作胺基酸定序的結果顯示ALDH3和 χ-ADH同屬固定型 (constant type)，和ADH族及ALDH族中屬變異型(variable type)的其他成員不同^(17,18)。

　　酒精的藥理作用受到器官或組織細胞內的乙醇與乙醛濃度影響，此亦和它們在血液內的濃度相關。為探討此深具臨床醫學涵義的問題，我們作過系列研究，企圖將酒精作用之標靶器官(target organ)肝、口腔、食道、胃、腸及肺的ADH和ALDH同功酶型、對偶基因表現型和酶活性作一關聯分析^(19-25)。我們發現高Km及高Vmax的第四類 μ-ADH僅在人的上消化道黏膜大量表現，而低Km的ALDH2在上下消化道黏膜幾乎不表現。我們提出在酒精代謝過程中，這會造成細胞內乙醛堆積，乙醛為已知的致癌劑，因此可部分解釋為何酒癮患者較易罹患口腔癌、食道癌或大腸癌^(21-23)。乙醇在人肝氧化及對新陳代謝的影響參見圖一。乙醛的生理和病理效應參見圖二。

　

　　飲酒後，乙醇在胃和小腸吸收，經門靜脈輸入肝，在此段尚未進入周邊血液循環之前的代謝稱為酒精初越代謝 (first-pass metabolism，簡稱FPM)。FPM的多寡會影響酒精的生體可用率 (bioavailability)，因此關係到酒醉駕車及酒精的器官傷害。這個課題近年引起研究熱潮，並對FPM主要發生的部位何在及有無性別差異爭議不斷。我們所作人ADH族組織分佈的研究顯示，酒精的FPM主要發生在肝，胃的參與甚微，且胃黏膜ADH和ALDH均無年齡或性別差異存在^(24-26)。由於乙醇在人體內排除可達Michaelis-Menten飽和動力學，依據我們所作ADH族成員的基質飽和及基質抑制實驗並應用所推導的動力方程式作模擬，結果顯示高Km的肝 π-ADH和胃 μ-ADH能有效參與FPM^(26,27)。

　　酗酒的母親可能生出額面畸形、智力障礙的胎兒，稱為酒精胎兒症候群 (fetal alcohol syndrome，簡稱FAS)。FAS對西方國家造成沉重的醫療支出和社會負擔，所以成為重要的研究課題，惟其致病的分子機制迄今未明。我們所作的研究顯示，人ADH族第一、二、四類成員可催化維甲醇 (retinol) 的氧化，乙醇對維甲醇呈競爭型抑制，抑制常數值在37 μM和11 mM之間。我們所作動力方程式模擬，顯示在社交飲酒血液所達的乙醇濃度範圍即可有效抑制維甲醇氧化。此氧化步驟決定維甲酸 (retinoic acid) 生合成的速率，乙醇的抑制可能降低細胞內維甲酸的濃度⁽²⁷⁾。維甲酸是脊椎動物表皮細胞分化和胚胎發育的重要調控因子，因此我們提出假說，推測由於維甲酸在細胞內的平衡(homeostasis)受到乙醇阻斷，導致發生酒精胎兒症候群及酒精引發的皮膚病變和上下消化道癌⁽²⁷⁾。

　　1994年在澳洲舉行第七屆Congress of the International Society for Biomedical Research on Alcoholism，其中Symposium on Alcohol and Aldehyde Metabolizing Systems筆者受邀演講，講題是“ Alcohol dehydrogenase—Enzymology and metabolism”。1996年在美國舉行第八屆International Symposium on the Enzymology and Molecular Biology of Carbonyl Metabolism，筆者受邀演講“Expression, activities and kinetic mechanism of human stomach alcohol dehydrogenase”。1997年在瑞典舉行第六屆Congress of the European Society for Biomedical Research on Alcoholism，筆者和瑞典Karolinska Institute的J.-O. Höög教授共同主持Symposium on Molecular Aspects of Alcohol Metabolism，並發表演講“Genetic polymorphism and activity of human liver alcohol and aldehyde dehydrogenases: Inference for first-pass metabolism of ethanol”。1998年在義大利舉行第九屆International Symposium on the Enzymology and Molecular Biology of Carbonyl Metabolism，筆者受邀演講“Steady-state kinetic mechanism of human alcohol dehydrogenase family. Implications for functional classification and ethanol/retinol metabolism”。上面四個演講內容涵蓋前述實驗室已發表的工作。

三、單核苷酸多形性與酒癮

　　人類基因體單核苷酸多形性 (single nucleotide polymorphism，簡稱SNP) 產生催化性質互異的ADH和ALDH對偶同功酶，稱為功能多形性 (functional polymorphism)^(8,28)。人類對偶基因變異和酒癮形成之間的關係一直是酒精研究領域的重要議題。我們提出假說，在東方人的族群中，由於ADH2*2和ADH3*1基因分別決定高活性的β₂-ADH和γ₁-ADH，在肝臟乙醇可轉化成較多的乙醛，而ALDH2*2決定失活的ALDH2次單元，降低乙醛轉化成乙酸的速率。不論乙醇分解速率增加或乙醛分解速率降低，均會造成乙醛在肝和血液堆積，引發酒精敏感反應 (alcohol sensitivity) (圖二)。所以我們推測具ADH2*2、ADH3*1或ALDH2*2基因的國人較不易罹患酒癮。為要檢視這項預測，我們曾分析50位男性酒精依賴漢人及50位正常對照組的對偶基因型並第一個提出報告，分子遺傳的統計證據支持ADH2*2、ADH3*1和ALDH2*2均是東方人族群酒癮保護的生物因子⁽²⁹⁾。由於台灣原住民的酒精依賴盛行率超過漢人10倍^(3,4)，為瞭解除社會和文化因素外，其中是否受遺傳因子影響，我們的研究發現原住民族群的ALDH2*2分佈頻數甚低 (5%，相對照漢族則達30%)，這成為原住民酒癮盛行率偏高的重要生物因由⁽³⁰⁾。我們亦發現漢族酒精肝硬化患者的ALDH2*2頻數顯著較正常對照組為低，其ALDH2*1/*2異對偶基因型的發生率則有高於無肝病酒精依賴者的趨勢，顯示乙醛可能參與肝的酒精性硬化病變⁽³¹⁾。至於酒精代謝酶細胞色素CYP2E1基因5’側端區的點突變，我們並未發現和漢族與原住民酒癮或酒精性肝硬化有顯著關聯⁽³²⁾。

　　為要探討在酒癮形成中ADH和ALDH對偶基因之間的交互作用，我們最近將漢族酒精依賴人數增至420位，正常對照組達689位。我們的結果修訂了以前的假說。應用單套型體相對頻率 (relative haplotype) 分析，我們最先發現ADH3基因並非關聯酒癮，原先發現有關聯是因為它和ADH2對偶基因之間呈連鎖不均衡 (linkage disequilibrium) 的緣故^(33,34)。這和過去文獻報告，同在4號染色體的ADH2和ADH3位置相鄰，兩者間隔僅15 kb的結果相符。我們進一步作多項式邏輯迴歸 (multiple logistic regression) 分析，發現ADH2和ALDH2的單核酶酸多形性對酒癮危險率並無預期的增效 (synergistic) 作用，顯示它們對酒癮感受性(susceptibility)的影響互相獨立。我們亦發現ALDH2*2對酒癮的保護呈現複雜的部分顯性 (partial dominance) 現象⁽³⁴⁾。我們發現世界迄今僅一例的ALDH2*2/*2同對偶基因型酒精依賴病患⁽³⁵⁾。從組合式基因型 (combinatorial genotype) 分析，我們報告漢人族群ADH2*2/*2-ALDH2*2/*2者的酒癮危險率是ADH2*1/*1 -ALDH2*1/*1的1%，後者在西方白人為通常的組合式基因型⁽³⁵⁾。

四、單核苷酸多形性、酒精排除率與酒精敏感反應

　　我們在420位漢族酒精依賴者中意外發現一例屬ALDH2*2/*2 同對偶基因型⁽³⁵⁾，Higuchi和同工調查1300位日本酒精依賴者未曾發現一例屬此基因型，顯示單苷酶酸多形性之ALDH2*2/*2作為單一的生物因子即可接近完全保護東方人不得酒癮。為嘗試解釋ALDH2*2/*2能如此強效保護的生理基礎，我們設計實驗將正常男性漢人依基因型分成三組，ALDH2*1/*1、ALDH2*1/*2和ALDH2*2/*2，他們的ADH對偶基因型均控制為ADH2*2/*2和ADH3*1/*1。每位飲每公斤體重0.2克酒精後 (相當於350毫升鋁罐裝台灣啤酒的乙醇含量)，2小時內測量血液乙醇和乙醛濃度變化，心臟和顱內外血管血流動力反應及主觀感覺⁽³⁶⁾。我們發現ALDH2*2/*2變異型同對偶基因組，血中乙醇和乙醛的濃度時間曲線下的面積 (area under the time-concentration curve，簡稱AUC) 分別是ALDH2*1/*2異對偶基因組的1.4和4.7倍，是ALDH2*1/*1正常型同對偶基因組的2.6和223倍。變異型ALDH2*2/*2的乙醇排除率顯著低於正常型 ⁽³⁶⁾，這可歸因於肝ADH的酶活性受到產物乙醛的抑制^(7,8)。

　　變異型ALDH2*2/*2在飲酒後2小時，血中乙醛仍持續高量堆積，造成心搏持續加速，心輸出量持續增加，舒張壓持續下降，全身血管阻力持續降低，面動脈、頸總動脈和內頸動脈血流速率持續降低，同時持續產生顯著的整體不舒適的感覺⁽³⁶⁾。我們因此推論即使變異型ALDH2*2/*2飲少量酒，仍會造成血液中乙醛持續堆積，引發強烈心臟血管反應，產生整體不舒適感覺，導致無法大量飲酒甚至拒絕飲酒，所以他們能受到保護不得酒癮。至於我們發現唯僅一例的變異型ALDH2*2/*2酒精依賴患者，他為要適應先天乙醛代謝異常 (inborn error of acetaldehyde metabolism) 的缺陷，從不濫飲(binge drinking)，而是整天持續小量啜飲3到5罐啤酒。他例外不被ALDH2*2/*2基因型保護，可能歸因於本身對乙醛的心臟血管效應不敏感 (innate insensitivity) 或產生耐受性 (tolerance) 的緣故⁽³⁵⁾。

　　1998年在丹麥舉行第九屆Congress of the International Society for Biomedical Research on Alcoholism，筆者受邀在Symposium on Molecular Biology of the Alcohol Dehydrogenases演講，講題是“Allelic variation of the alcohol dehydrogenase genes and alcoholism in Asians”。1999年在德國舉行International Titisee Symposium on Health Effects of Alcohol Intake，筆者受邀擔任研討會的第一位講員，講題“Interaction of functional polymorphisms of alcohol metabolic genes and alcohol metabolism in Asian alcoholics”。2000年第二十三屆Annual Scientific Meeting of the American Research Society on Alcoholism，筆者受邀在Symposium on Genetic and Environmental Influences on Alcohol Metabolism in Humans演講，講題“ALDH2 polymorphism and alcohol metabolism”。同年在美國舉行第十屆International Symposium on the Enzymology and Molecular Biology of Carbonyl Metabolism，筆者受邀擔任其中主題是醛脫氫酶的四個議程之一的座長，並演講“Dominance of human ALDH2*2 variant gene allele: Influence on liver enzyme activity/content, alcohol pharmacokinetics, and susceptibility to alcoholism”。筆者上面四個演講內容包括前述已發表工作及實驗室尚未發表的結果。

五、結語和前瞻

　　酒癮屬行為疾病，其發生和演變有多種基因參與，包括基因與基因之間及基因與環境之間交互影響。醇脫氫酶和醛脫氫酶是人體主要的酒精代謝酶系統，酒精的藥理作用及細胞毒性和乙醇及代謝產物乙醛濃度相關。ADH2和ALDH2是迄今唯一被確認的酒癮基因，二者對偶基因的功能多形性影響乙醇和乙醛的藥物動力學及對腦、心臟血管、肝、上下消化道的藥物效力學，進而影響人類的飲酒行為、酒癮和酒精器官傷害的發生。

　　美、英主導國際合作的人類基因體計畫 (Human Genome Project)，精確定序工作訂於2003年，非常可能會提前完成。生物醫學界可預見快速篩選和測試更多的酒癮候選基因 (candidate genes)，進而探討多重基因疾病 (polygenic diseases)，包括酒癮、癌、高血壓、糖尿病等，致病基因之間如何交互作用產生病變，是將來必然的挑戰。預計2005年之前國際合作完成小鼠基因體的定序，配合基因轉殖和基因剔除技術發展，將成為研究人類多重基因疾病不可缺少的動物模式。這些劃時代的突破與成就，加上資訊和生物科技進展一日千里，令生物醫學界的工作者興奮雀躍且摩拳擦掌拭目以待。

六、誌謝

　　科學研究首重團隊，維持研究優勢和不斷突破，需要在國際和國內有專家合作，實驗室的研究群也須達到臨界人力值。筆者衷心感謝國家科學委員會和後來國家衛生研究院長期經費補助，從1984年元月自美進修返國後，17年來能有機會逐步建立發展自己的實驗室，有機會在摸索嘗試中尋到自己的研究方向。

　　我感謝美國Indiana University生化和分子生物學系及醫學系Distinguished Professor厲鼎凱，帶領我 (1980-1983) 進入酒精研究領域，是我的啟蒙老師。厲教授多年來的關懷與合作情誼令我珍惜。我曾於1989年赴瑞典Karolinska Institute，在化學I系Hans Jörnvall教授的實驗室訪問研究6個月，彼此一直保持合作與珍貴友誼。榮民總醫院一般外科吳秋文主任，台北市立療養院成人精神科陳喬琪主任，台大醫學院精神科胡海國教授，三軍總醫院胸腔外科李世俊主任、直腸外科饒樹文主任和精神醫學部陸汝斌主任在過去多年合作中慷慨無私支持，他們的友誼令我珍惜。國防醫學院生化學科王明芳講師和三軍總醫院廖錦霞前助理研究員作我長期的研究夥伴，他們對研究生和研究助理的訓練及維持實驗室運作功不可沒。

　　我指導已畢業的國防醫學院生命科學研究所和醫學科學研究所博士班研究生韓繼利、彭家勛醫師、陳益乾醫師、賴慶隆及仍在就讀的博士班研究生周初昉、李守倫，他們願意加入實驗室，對提升研究水準有決定性的貢獻。我指導畢業的生化研究所碩士班研究生迄今16位，和其中多位仍保持友誼聯繫，參加我研究計畫的專任研究助理迄今有22位，在此不一一記名。我熱愛科學，研究成為我生活的重心。過去17年來我能有機會指導訓練年輕人進入研究領域，培養他們嚴謹科研態度和踏實工作習慣，並與他們互動。我也從他們學習，尤其是博士班研究生各有自己的學業背景和專長。對這一切我深感幸運、安慰和喜悅。

七、參考文獻

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2. Liu, J.-D., Leung, K.-W., Wang, C.-K., Liao, L.-Y., Wang, C.-S., Chen, P.-H., Chen, C.-C. and Yeh, E.-K. (1998) Alcohol-related problems in Taiwan with particular emphasis on alcoholic liver diseases. Alcohol. Clin. Exp. Res. 22:164S-169S.
3. Cheng, A.T.-A. and Chen, W.-J. (1995) Alcoholism among four aboriginal groups in Taiwan: High prevalences and their implications. Alcohol. Clin. Exp. Res. 19:81-91.
4. Helzer, J. E., Canino, G. J., Yeh, E.-K., Bland, R. C., Lee, C. K., Hwu, H.-G. and Newman S. (1990) Alcoholism—North America and Asia. A comparison of population surveys with the diagnostic interview schedule. Arch. Gen. Psychiatry 47:313-319.
5. Yin, S.-J. and Li, T.-K. (1989) Genetic polymorphism and properties of human alcohol and aldehyde dehydrogenases: Implications for ethanol metabolism and toxicity, in “Molecular Mechanisms of Alcohol: Neurobiology and Metabolism,” G. Y. Sun, P. K. Rudeen, W. G. Wood, Y.-H. Wei and A. Y. Sun, eds., Humana Press, Clifton, pp. 227-247.
6. Yin, S.-J. (1996) Alcohol dehydrogenase: Enzymology and metabolism, in “The Biology of Alcohol Problems,” J. B. Saunders and J. B. Whitfield, eds., Elsevier Science, Oxford, pp. 113-119.
7. Yin, S.-J., Han, C.-L., Lee, A.-I. and Wu, C.-W. (1999) Human alcohol dehydrogenase family. Functional classification, ethanol/retinol metabolism, and medical implications. Adv. Exp. Med. Biol. 463:265-274.
8. Yin, S.-J. and Agarwal, D. P. (2001) Functional polymorphism of alcohol and aldehyde dehydrogenases: Alcohol metabolism, alcoholism, and alcohol-induced organ damage, in “Alcohol in Health and Disease,” D. P. Agarwal and H. K. Seitz, eds., Marcel Dekker, New York, pp. 1-26.
9. Yin, S.-J., Bosron, W. F., Li, T.-K., Ohnishi, K., Okuda, K., Ishii, H. and Tsuchiya, M. (1984) Polymorphism of human liver alcohol dehydrogenase: Indentification of ADH2 2-1 and ADH2 2-2 phenotypes in the Japanese by isoelectric focusing. Biochem. Genet. 22:169-180.
10. Yin, S.-J., Bosron, W. F., Magnes, L. J. and Li, T.-K. (1984) Human liver alcohol dehydrogenase: Purification and kinetic characterization of the β₂β₂, β₂β₁, αβ₂, and β₂γ₁ “Oriental” isoenzymes. Biochemistry 23:5847-5853.
11. Bosron, W. F., Yin, S.-J., Dwulet, F. E. and Li, T.-K. (1986) Selective carboxymethylation of cysteine 174 of the β₂β₂ and β₁β₁ human liver alcohol dehydrogenase isoenzymes by iodoacetate. Biochemistry 25:1876-1881.
12. Yin, S.-J., Wang, M.-F., Liao, C.-S., Chen, C.-M. and Wu, C.-W. (1990) Indentification of a human stomach alcohol dehydrogenase with distinctive kinetic properties. Biochem. Int. 22:829-835.
13. Duester, G., Farrés, J., Felder, M. R., Holmes, R., Höög, J.-O., Parés, X., Plapp, B. V., Yin, S.-J. and Jörnvall, H. (1999) Recommended nomenclature for the vertebrate alcohol dehydrogenase gene family. Biochem. Pharmacol. 58:389–395.
14. Yin, S.-J., Wang, M.-F., Han, C.-L. and Wang, S.-L. (1995) Substrate binding pocket structure of human aldehyde dehydrogenases. A substrate specificity approach. Adv. Exp. Med. Biol. 372:9-16.
15. Yin, S.-J., Liao, C.-S., Wang, S.-L., Chen, Y.-J. and Wu, C.-W. (1989) Kinetic evidence for human liver and stomach aldehyde dehydrogenase-3 representing a unique class of isozymes. Biochem. Genet. 27:321-331.
16. Wang, S.-L., Wu, C.-W., Cheng, T.-C. and Yin, S.-J. (1990) Isolation of high-Km aldehyde dehydrogenase isoenzymes from human gastric mucosa. Biochem. Int. 22:199-204.
17. Yin, S.-J., Vagelopoulos, N., Wang, S.-L. and Jörnvall, H. (1991) Structural features of stomach aldehyde dehydrogeanse distinguish dimeric aldehyde dehydrogenase as a “variable” enzyme. “Variable” and “constant” enzymes within the alcohol and aldehyde dehydrogenase families. FEBS Lett. 283:85-88.
18. Yin, S.-J., Wang, S.-L., Liao, C.-S. and Jörnvall, H. (1993) Human high-Km aldehyde dehydrogenase (ALDH3): Molecular, kinetic and structural features. Adv. Exp. Med. Biol. 328:87-98.
19. Yin, S.-J., Cheng, T.-C., Chang, C.-P., Chen, Y.-J., Chao, Y.-C., Tang, H.-S., Chang, T.-M. and Wu, C.-W. (1988) Human stomach alcohol and aldehyde dehydrogenases(ALDH): A genetic model proposed for ALDH III isoenzymes. Biochem. Genet. 26:343-360.
20. Yin, S.-J., Liao, C.-S., Chen, C.-M., Fan, F.-T. and Lee, S.-C. (1992) Genetic polymorphism and activities of human lung alcohol and aldehyde dehydrogenases: Implications for ethanol metabolism and cytotoxicity. Biochem. Genet. 30:203-215.
21. Yin, S.-J., Chou, F.-J., Chao, S.-F., Tsai, S.-F., Liao, C.-S., Wang, S.-L., Wu, C.-W. and Lee, S.-C. (1993) Alcohol and aldehyde dehydrogenases in human esophagus. Comparison with the stomach enzyme activities. Alcohol. Clin. Exp. Res. 17:376-381.
22. Yin, S.-J., Liao, C.-S., Lee, Y.-C., Wu, C.-W. and Jao, S.-W. (1994) Genetic polymorphism and activities of human colon alcohol and aldehyde dehydrogenases: No gender and age differences. Alcohol. Clin. Exp. Res. 18:1256-1260.
23. Dong, Y.-J., Peng, T.-K. and Yin, S.-J. (1996) Expression and activities of class IV alcohol dehydrogenase and class III aldehyde dehydrogenase in human mouth. Alcohol 13:257-262.
24. Yin, S.-J., Liao, C-S., Wu, C.-W., Li, T.-T., Chen, L.-L., Lai, C.-L. and Tsao, T.-Y. (1997) Human stomach alcohol and aldehyde dehydrogenases: Comparison of expression pattern and activities in alimentary tract. Gastroenterology 112:766-775.
25. Lai, C.-L., Chao, Y.-C., Chen, Y.-C., Liao, C.-S., Chen, M.-C., Liu, Y.-C. and Yin, S.-J. (2000) No sex and age influence on the expression pattern and activities of human gastric alcohol and aldehyde dehydrogenases. Alcohol. Clin. Exp. Res. 24:1625-1632.
26. Yin, S.-J., Han, C.-L., Liao, C.-S. and Wu, C.-W. (1997) Expression, activities and kinetic mechanism of human stomach alcohol dehydrogenase. Inference for first-pass metabolism of ethanol in mammals. Adv. Exp. Med. Biol. 414:347-355.
27. Han, C.-L., Liao, C.-S., Wu, C-W., Hwong, C.-L., Lee, A.-R. and Yin, S.-J. (1998) Contribution to first-pass metabolism of ethanol and inhibition by ethanol for retinol oxidation in human alcohol dehydrogenase family. Implications for etiology of fetal alcohol syndrome and alcohol-related diseases. Eur. J. Biochem. 254:25-31.
28. Li, T.-K., Yin, S.-J., O’Connor, S., Ramchandani, V. A. and Crabb, D. W. (2001) Genetic and environmental influences on alcohol metabolism in humans. Alcohol. Clin. Exp. Res. 25:1-9.
29. Thomasson, H. R., Edenberg, H. J., Crabb, D. W., Mai, X.-L., Jerome, R. E., Li, T.-K., Wang, S.-P., Lin, Y.-T., Lu, R.-B. and Yin, S.-J. (1991) Alcohol and aldehyde dehydrogenase genotypes and alcoholism in Chinese men. Am. J. Hum. Genet. 48:677-681.
30. Thomasson, H. R., Crabb, D. W., Edenberg, H. J., Li, T.-K., Hwu, H.-G., Chen, C.-C., Yeh, E.-K. and Yin, S.-J. (1994) Low frequency of the ADH2*2 allele among Atayal natives of Taiwan with alcohol use disorders. Alcohol. Clin. Exp. Res. 18:640-643.
31. Chao, Y.-C., Liou, S.-R., Chung, Y.-Y., Tang, H.-S., Hsu, C.-T., Li, T.-K. and Yin, S.-J. (1994) Polymorphism of alcohol and aldehyde dehydrogenase genes and alcoholic cirrhosis in Chinese patients. Hepatology 19:360-366.
32. Carr, L. G., Yi, I. S., Li, T.-K. and Yin, S.-J. (1996) Cytochrome CYP2E1 genotypes, alcoholism and alcoholic cirrhosis in Han Chinese and Atayal natives of Taiwan. Alcohol. Clin. Exp. Res. 20:43-46.
33. Osier, M., Pakstis, A. J., Kidd, J. R., Lee, J.-F., Yin, S.-J., Ko, H.-C., Edenberg, H. J., Lu, R.-B. and Kidd, K. K. (1999) Linkage disequilibrium at the ADH2 and ADH3 loci and risk of alcoholism. Am. J. Hum. Genet. 64:1147–1157.
34. Chen, C.-C., Lu, R.-B., Chen, Y.-C., Wang, M.-F., Chang, Y.-C., Li, T.-K. and Yin, S.-J. (1999) Interaction between the functional polymorphisms of the alcohol-metabolism genes in protection against alcoholism. Am. J. Hum. Genet. 65:795–807.
35. Chen, Y.-C., Lu, R.-B., Peng, G.-S., Wang, M.-F., Wang. H.-K., Ko, H.-C., Chang, Y.-C., Lu, J.-J., Li, T.-K. and Yin, S.-J. (1999) Alcohol metabolism and cardiovascular response in an alcoholic patient homozygous for the ALDH2*2 variant gene allele. Alcohol. Clin. Exp. Res. 23:1853–1860.
36. Peng, G.-S., Wang, M.-F., Chen, C.-Y., Luu, S.-U., Chou, H.-C., Li, T.-K. and Yin, S.-J. (1999) Involvement of acetaldehyde for full protection against alcoholism by homozygosity of the variant allele of mitochondrial aldehyde dehydrogenase gene in Asians. Pharmacogenetics 9:463–476.

(2)「2012年國防醫學院生化科所退休專題演講」

(a) 科主任介紹 slides (1–8)及演講 slides (9–70)

(b) Selected Pictures of Retirement Lecture and the Lab Members Reunion Dinner that Evening (15 photos)

(c) 醫學系三年級百餘位學生謝師感言( 他們在去年2011年春季二年級下學期時，曾修過我教的四週共16堂生物化學，涵蓋生物能量學、脂肪酸和胺基酸代謝、代謝管制與整合，較多涉及一些數學、物理、化學的基本觀念應用到生物及醫學，這對習慣於傳統用敘述事實的講授方式、靠記憶而輕理解思辨融會貫通來學習的醫科學生稍有困難。在我教部分的段考50題選擇題，60分及格率為59 %，較我過去一般約六至七成的及格率為偏低 )。由於事過快一年，我未想到他們全體學生會親寫謝師卡，並由來聽退休演講同學們代表交給我。當我仔細讀過每位學生寫出這些他們完全自發的話，感覺是我在國防教書研究逾30載最大欣慰與成就。每一代的努力，至終期望是下一代更好；科學理念、精神能在國內文化生根，是每一位科學工作者的期待。

(d) 生化科所同仁惜別贈言。

(e) 69歲生日學生賀卡及感言(這將是最後一次學生在實驗室為我舉辦慶生午餐和蛋糕。我計畫明年滿70歲前結束研究並關閉實驗室和辦公室。早年父母申報子女戶籍身份證都用陰曆，現在學生能留心查記我每年生日陽曆的日期，深覺溫馨與窩心。卡片上學生誠摯感言，成為我結束學術生涯之前一個美好的回憶。又，除永彬、毓周是我最後兩位博士班研究生外，其餘都是建平和曉屏的學生。我們實驗室就像一個大家庭般親密，這是中國儒家文化的特質)。

(2a) 科主任介紹 Slides (1–8)及演講 Slides (9–70)

(2b) Selected Pictures of Retirement Lecture and the Lab Members Reunion Dinner that Evening (15 photos)

(2c) 2012年1月12日退休演講後，曾於2011年春我教過的醫學系學生親送謝師感言   (共4大張卡片)

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(第3張)	(第4張)

 (2d) 生化科所全體同仁惜別贈言，對每一位同仁的祝福我銘感於心。

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(2e) 學生巧思繪製生日賀卡封面及感言，是我人生暮年珍惜的回憶。

(卡片信封封面)

(卡片封頁)

(3)「國際酒癮生物醫學研究學會2012年通訊」

「國際酒癮生物醫學研究學會」(International Society for Biomedical Research on Alcoholism，簡稱ISBRA)，現有會員682位，來自45個國家，理事會(board of directors)的理事含正、副會長共12位(學會章程規定，由全體會員選出南北美洲、歐洲、亞洲太平洋三區的每區理事各4位，任期四年，最多三任)。現今理事的國籍分佈分別是美 (4)、德 (3)、法 (1)、日 (2)、澳 (1)、台灣 (1)。我深感欣慰的是實驗室研究團隊全體努力，在本土默默耕耘28年(1984–

2012)，能首次有台灣學者進入理事會；雖微不足道但很高興在國家的國際處境維艱歲月，見到中華民國的國旗出現於學會通訊封頁(見後ISBRA2012年6月Newsletter左排三)。

Newsletter website: http://www.isbra.com/pdf/2012-0601_newsletter_2.1.3_ordered.pdf

(4)「2014年慈濟大學醫學科學研究所研究典範專題演講」(2014年5月8日)

(5) 「2015年自國際酒癮學術期刊ACER領域編輯退休通信」

Alcoholism: Clinical and Experimental Research 是美國酒癮研究學會 (Research Society on Alcoholism) 和國際酒癮生物醫學研究學會 (International Society for Biomedical Research on Alcoholism) 共同出版的學會期刊。該期刊在2015年初的最近版2012 ISI Journal Citation Reports: impact factor, 3.421; ranking in Substance Abuse category, 3/16 (19%)。

(5a) 2015年1月ACER的Managing Editor Mary Newcomb 關於我今年初自Field Editor退休的三份通信 (半年前我已寫信告知她此項決定)。三年多來 (2011.8.－2014.12.)，編輯部辦公室分稿請我負責處理三個酒精研究領域：Genetics Human and Laboratory Animals、Pharmacokinetics and Metabolism、Pathology Human-Animal中的32件來稿。一般我會先篩選邀請兩位專家評審，根據審查意見和評等再做最後裁定。共刊登了10件，接受率為31%。這和ACER收到全部稿件的年平均接受率相近，即退稿約佔七成。

------------------------------------------------------------------------------------------------------------------------

寄件者: Mary Newcomb [acerjournal@earthlink.net]

寄件日期: 2015/1/6 [星期二] 下午 04:32

收件者: Shih-Jiun Yin (Paul Yin)

主旨: Re: Your retirement

附件: Paul Yin Thank you.docx (40KB)

Dear Dr. Yin,

Dr. Nagy, Associate Editor for the Board of Field Editors, has asked that I send you the attached letter regarding your retirement.

I want to express my personal thanks for all your help over your years as Field Editor.  While I know you are on to bigger and better things, I am very sad to see you go.  I wish all the Field Editors were as easygoing, helpful and timely as you have been.  It has been a pleasure working with you.

I hope 2015 is a wonderful year for you!

Best wishes in all your future endeavors,

Mary

Mary L. Newcomb

Managing Editor

Alcoholism: Clinical & Experimental Research

5017 East 12^th Street

Indianapolis, IN 46201

acerjournal@earthlink.net

------------------------------------------------------------------------------------------------------------------------

寄件者: Shih-Jiun Yin (Paul Yin)

寄件日期: 2015/1/7 [星期三] 上午 09:26

收件者: Mary Newcomb

主旨: RE: Your retirement

Dear Mary,

Thanks for sending Dr. Nagy’s letter. I really appreciate your kind words. It has been personally very delightful and also a good learning experience working with you, too. Maybe I had once stayed in Indianapolis over 3 years (that’s my first time leaving my home country) back in the early 1980s that makes me feel familiar with a native of Indiana like you as friends, even though we didn’t have chance to see each other afterward.

May God be with you and bless you.

Warmly in God’s love and blessings,

Paul     

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寄件者: Mary Newcomb [acerjournal@earthlink.net]

寄件日期: 2015/1/7 [星期三] 上午 10:12

收件者: Shih-Jiun Yin (Paul Yin)

主旨: RE: Your retirement

Thank you, Paul.

I appreciate all your kind words.  You are so sweet!  I will miss you. 

Warm wishes,

Mary

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(5b) 2015年1月ACER Associate Editor Laura Nagy 給我的退休致謝信

Alcoholism: Clinical & Experimental Research

Editorial Office

5017 East 12^th Street

Indianapolis, IN 46201

January 4, 2015

Shih-Jiun Yin, Ph.D.

National Defense Medical Center

Department of Biochemistry

161, Min-Chuan East Road Section 6

Taipei 11453

Taiwan

Dear Paul,

On behalf of both the Editorial Board of Alcoholism Clinical and Experimental Research and the journal’s management staff, I would like to extend our gratitude for your exemplary service as a Field Editor since 2011. We are sorry to see you retire as Field Editor and hope that you have enjoyed your service for the journal. I am continually impressed by the volunteer spirit within our community of scientists; it is really these voluntary efforts that we squeeze into our busy days and weekends that allows us to make important progress in research and discovery!

Thanks again for your service!

Best regards,

Laura E. Nagy, PhD

Associate Editor, Alcoholism Experimental and Clinical Research

(6) 「2017年紀毓周發表論文受邀毒理及製藥科技國際會議演講」(含新增4份，共6份，國際會議邀請演講函)

近日我收到今年6月在法國巴黎的Euro Toxicology 2017 Conference 和9月在大陸西安的15th Annual Congress of International Drug Discovery Science and Technology 大會的邀請演講，講題均指定我指導最後一位博士生毓周2016年8月發表在期刊Chemico-Biological Interactions的Ethanol oxidation and the inhibition by drugs in human liver, stomach and small intestine: Quantitative assessment with numerical organ modeling of alcohol dehydrogenase isozymes. 這令我感到相當意外，首先發表的期刊不是頂級，其次毒理和製藥科技都是較酒精與酒癮更廣的學術領域，他們竟然會注意重視這篇論文。(見下附我2月24日寫給論文共同作者的信及二份邀請函。)

基礎科學研究是條漫長自我定向，步步深耕，不斷追求突破的路。很高興我們團隊像接力賽跑，經過二十餘年堅持不懈，一棒接一棒終於將複雜的人類酒精代謝議題觸及系統毒理和數學器官模型的範疇。雖然僅是剛剛起步，毓周和我亦樂在其中。2017年2月24日出版的Science，在804頁History of Science欄Craig A. Tovey寫的一篇書評，“In defense of basic research: A 1939 essay resonates today, persuasively advocating for science for science’s sake” 深得我心，摘錄其中二小段如下：

“Flexner believed in the intrinsic value of the scientist’s curiosity and in the pursuit of knowledge for its own sake. His 1939 essay, The Usefulness of Useless Knowledge, advocates for unfettered inquiry that, paradoxically and unexpectedly, has often resulted in extraordinary utility.”

“Flexner is perhaps most eloquent when he is most general, portraying both the arts and the sciences as expressions of the free human spirit: ‘A poem, a symphony, a painting, a mathematical truth, a new scientific fact, all bear in themselves all the justification that universities, colleges, and institutes of research need or require.’ ”

新增：收到今年12月在西班牙馬德里舉行「9^th International Congress on Renewable Energy and Advanced Biofuels的邀請演講」，我不打算參加 (見最後附我7月14日給永彬、毓周短信及大會相當禮遇的邀請函)。

另：又收到2017年10月在倫敦舉行「2^nd Euro Global Summit and Expo on Biomass and Bioenergy」和11月在新加坡舉行「10^th World Congress of Vaccine-2017 Singapore」，及2018年5月在西班牙巴塞隆納舉行「10^th International Conference on Genomics & Molecular Biology」的邀請演講，三份大會邀請講員函亦併附在最後。

今年著實出我意外，竟收到6個國際會議邀請演講，均非我專研的酒精與酒癮領域，這是過去未曾有的事。這6個大會的主題廣泛，僅與我自退休後5年(2012－2016)實驗室發表的10篇著作，有間接關聯，或許仍引起他們興趣和重視，顯示出我們工作的跨領域性質。

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寄件者: Shih-Jiun Yin (Paul Yin)

寄件日期: 2017/2/24 [星期五] 下午 03:57

收件者: Yu-Chou Chi; Shou-Lun Lee; Ching-Long Lai; Yung-Pin Lee; Shiao-Pieng Lee; Chien-Ping Chiang

主旨: Yu-Chou's work has been invited to give a talk in two 2017 international congresses on toxicology and drug discovery science/technology

附件: Attachment 1 (4KB) Attachment 2 (5KB)

Praise God! Recently I unexpectedly received speaker invitations on the title of Yu-Chou’s 2016 CBI paper from Euro Toxicology 2017 Conference themed ‘Paving Path for Quality Tox Connections’ to be held in Paris (attachment 1) and the 15th Annual Congress of International Drug Discovery Science and Technology-2017 in Xi’an (attachment 2). Yu-Chou’s paper represents our team work which ramped up over two decades reaching systems toxicology and mathematical organ modeling of the ethanol metabolism, a long-term goal of our research. But it was just a beginning. We are happy for Yu-Chou that his work has been noticed by the broader fields of toxicology and drug discovery/technology. I have no intention to take more speaking invitations 5 years after my retirement. Actually, I still vividly remembered 2012 Carbonyl Metabolism Meeting at a beautiful Danish royal summer palace at Ploen lakeside, Germany, and our postconference tours in northern Germany and Switzerland together with Ching-Long, Shou-Lun and his wife and son, that really was a perfect ending of my numerous research career conferences across America, Europe, Asia, Australia/New Zealand spanning nearly 30 years. By the way, Yu-Chou has become a Christian. Hope Ching-Long and Shou-Lun will join the rest of us in near future.

God bless you and be with you.

Paul

Attachment 1

From: Euro Toxicology 2017 [mailto:eurotoxicology@toxicologyconferences.org]

Sent: Monday, February 06, 2017 11:16 PM

To: Shih-Jiun Yin (Paul Yin)

Subject: Ethanol oxidation and the inhibition by drugs in human liver, stomach and small intestine

Dear Dr. Shih-Jiun Yin,

Greetings!

We take the honor to solicit you to the Euro Toxicology 2017 Conference themed .Paving Path for Quality Tox Connections·.

Your write-up; Ethanol oxidation and the inhibition by drugs in human liver, stomach and small intestine: Quantitative assessment with numerical organ modeling of alcohol dehydrogenase isozymes: goes well in line with the sessions to be roofed in the conference. And it’d be a pleasure to take in more info about it along with your research crew as our Speaker.

I am glad to know your feasibility on June 22-24, 2017 as the conference scheduled on these dates in Paris, France. And would be much pleased to give more information about the Speaker invitation.

Conference Sessions on which you may orate your lecture http://toxicology.global-summit.com/europe/call-for-abstracts.php

Good day :)

Best Regards,

Valentina Leyva

Program Director

Euro Toxicology 2017

Conference Series UK

+1-702-508-5197 Ext: 8066 | eurotoxicology@conferenceseries.net

conferenceseries.com

Attachment 2

寄件者: Catherine <irene5@2017-iddst.com>
寄件日期: 2017年2月23日星期四 上午 12:58
收件者: Shih-Jiun Yin (Paul Yin)
主旨: Distinguished Speech Invited to IDDST-2017, Xi'an, China
 
Dear Shih-Jiun Yin,
 
I'm writing to follow-up my last invitation as below, would you please give me a tentative reply? Thank you very much.
 
It is our great pleasure to welcome you to join the 15th Annual Congress of International Drug Discovery Science and Technology-2017, November 9-11, 2017 at Xi’an, China. I sincerely welcome you to give a speech about Ethanol oxidation and the inhibition by drugs in human liver, stomach and small intestine: Quantitat... at Section 505 : Novel Models for Drug Discovery, we sincerely hope you could come and share your experience to let others have a chance to gain a lot. We would like also take this opportunity to talk about latest news at our conference.
 
Please click the following website for details: http://www.iddst.com/iddst2017/default.asp.
 
The organizing committee shows great interest in your recent research and hope that you can make a speech, we believe your participation will add great value for IDDST-2017.
 
The IDDST congress, initiated by BIT Life Sciences in 2003, is dedicated to supporting the pharmaceutical professionals and bioscientists to exchange ideas, network, seek partnership overseas, pinpoint and identify opportunities and global drug R & D market demand, get updated on the latest breakthroughs in innovative new drugs, networking, and explore business development in across cultural environment. With 14 years’ of persistent efforts, the IDDST congress has successfully attracted more than 8,000 world renowned speakers with over 50,000 professionals around the world as a leading international event for our drug discovery community.
 
If you have any precious suggestions on IDDST or if you are ready to attend the event, please reply this email and send your speech title to us at your earliest convenient. 
 
Join the magnificent scientific and social programs to maximize your network and partner hunting in a free communication meeting environment!
 
Yours Sincerely,
 
Ms. Catherine Zhang
The Organizing Committee of IDDST-2017

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寄件者： Shih-Jiun Yin (Paul Yin)

寄件日期： 2017/7/14 [星期五] 上午 08:18

收件者： Yung-Pin Lee; Yu-Chou Chi

主旨： FW: Invitation to be an honorable speaker for the Advanced Biofuels 2017 conference

Yung-Pin and Yu-Chou:

As said before, I am not going abroad to give talks any more (see below for a recent invitation). Ethanol is both a fuel for human metabolism and a biofuel for industry. We are interested in the former, a tiny field in the context of renewable energies and biofuels. But you can sense an increasing trend of cross-disciplinary integrations for modern science.

God bless you and be with you.

Paul

From: (3) Advanced Biofuels 2017 [mailto:advancedbiofuels@alliedconferences.org]

Sent:; Thursday, July 13, 2017 8:06 PM

To: Shih-Jiun Yin (Paul Yin)

Subject: RE: Invitation to be an honourable speaker for the Advanced Biofuels 2017 conference

Dear Dr. Shih-JiunYin ,

Greetings!

I am glad to reach you on behalf of Advanced Biofuels 2017 Organizing Committee, after having a view at your vast expertise and eminent contribution in the research relevant to Renewable energies and biofuels. We courteously welcome you as a Speaker for the upcoming 9^th International Congress on Renewable Energy and Advanced Biofuels from December 7-8, 2017 in Madrid, Spain.

The present conference strives to provide meaningful coverage on “Future fuels- A revolution in the field of energy”.

I would like to kindly notify you that in this conference, you have opportunity to attend multiple panels, workshops, affinity group lunches, forums, poster sessions, and interact with eminent personalities from all areas of Renewable energies and biofuels. Along with the above mentioned details you will have a chance to participate at the keynotes and leadership workshops and symposiums.

The vision of Advanced Biofuels 2017 is to provide a broad discussion on current research and development on Renewable energies and biofuels that will coherently help in providing better future.

For more details Please visit Advanced Biofuels 2017 Website

We are very confident that we will definitely offer you an unforgettable experience in exploring new prospects.

Hope to read back from you for any clarifications.

With Kind Regards,
Cathy Ryan
Program Manager
Advanced Biofuels 2017
Allied Academies
40 Bloomsbury Way Lower Ground Floor
London, United Kingdom
WC1A 2SE
Call: (828) 214-3944

E-mail: advancedbiofuels@alliedconferences.org

www.alliedacademies.com

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又加五份邀請講員函(4－8)：

From: (4) Euro Biomass 2017 [mailto:eurobiomass@annualconferences.org]

Sent: Thursday, July 20, 2017 10:14 PM

To: Shih-Jiun Yin (Paul Yin)

Subject: Gentle remainder - Speaker Invitation for Euro Biomass 2017 | London | UK

2nd Euro Global Summit and Expo on

Biomass and Bioenergy

October 12-13, 2017 London, UK

Dear Dr. Shih-Jiun Yin,

Greetings from Euro Biomass 2017!!!

As we have tried contacting earlier but couldn’t reach you because of your busy schedule, we want to give a gentle reminder to give us your valuable response regarding your presence to the 2nd Euro Global Summit and Expo on Biomass and Bioenergy.

On the behalf of organizing committee member of Euro Biomass -2017, we would like to invite you as a Speaker for 2nd Euro Global Summit and Expo on Biomass and Bioenergy, which is going to be held in London, UK during October 12-13, 2017.

CONFERENCE HIGHLIGHTS

Biomass Conversion Methods

Biomass Applications

Biomass Energy Resources

Bioenergy Transition

Supply Chain Management

Processes for Bioenergy

Bio-energy Conversion Methods

Biogas

Renewable Energy

Environmental Impact of Biomass

Biodiesel

Bioethanol

Advanced Biofuels

Biomass Market Analysis

Waste Biomass

Production of Biofuels

Pyrolysis

Landfill Gas as a Renewable Energy Resource

Biomass from Microbial Sources

Entrepreneurs Investment Meet

As your work has left great contributions to Biomass and Bioenergy field, your expertise and experience in this field of work will be an excellent addition to our programme on Euro Biomass 2017 conference (London, United Kingdom).

As, you are a symbol of success and inspiration for young researchers, your presence and thought provoking words will be a source of motivation for them. If you can spare some precious time and come to this pioneer conference we shall be honored.

Kindly have a glance at our conference website: Euro Biomass

We look forward to a positive response.

Feel free to contact us, we will be happy to assist you.

Best Regards

Camie Jones

Program Manager

Euro Biomass 2017

Kemp House, 152 City Road,

London EC1V 2NX, UK

Toll Free: +1-800-014-8923

Direct: (702) 508-5200 Ext: 8035

Email: eurobiomass@chemseries.com

From: (5) Monica Wu [mailto:wu.monica567@wcv2017singapore.com]

Sent: Thursday, July 20, 2017 3:12 PM

To: Shih-Jiun Yin (Paul Yin)

Subject: 527-Entitled to be a session speaker at the Immunology Forum of 10th World Congress of Vaccine-2017, Singapore

The 10^th World Congress of Vaccine-2017 Singapore

Theme: Accelerating Next Generation Vaccines R&D

Time: 15-17 November, 2017

Venue: Singapore

Dear Dr. Shih-Jiun Yin

This is Monica. How are you? I'm writing to follow-up my last invitation as below. Would you please give me a tentative reply? Thank you very much.

We are proud to announce The 10th World Congress of Vaccine-2017 Singapore is going to be held in Singapore during November 15-17, 2017. This is an invitation for you to join us in the Immunology of this congress as a Speaker in Session 713: Immuno Cytochemistry, Immunohistochemistry and Immunobiology while presenting about your latest research.

Track 1: Latest Research and Technologies in Vaccines Development

Track 2: Vaccines for Emerging and Re-Emerging Diseases

Track 3: Vaccines for Human Diseases

Track 4: Veterinary Vaccines

Track 5: Vaccines Production & Manufacturing

Track 6: Global Vaccines Market Trends and Regulations

Track 7: Hot Topics in Immunology Research

Track 8: Innovative Technology in Immunology

Track 9: Clinical Immunology

This unique international conference provides a platform for researchers and decision makers in immunology and vaccine to present their latest findings and learn about all the important developments in this fields. Many world's renowned experts and eminent scientists will participate in the conference.

I believe such an initiative will be the perfect opportunity and platform to highlight the high profile permanent vaccine & Immunology convention.

The conference covers a wide range of critically important themes from basic science to commercialization. Participants will explore the different research, business and investment activities occurring throughout the event.

Singapore, the conference place, whose weather there is pretty pleasant. In this place, you could either go visit the flower markets or enjoy the delicious seafood, bright sunshine, fresh air and beautiful scenery. I believe you will never forget it.

Sincerely yours,

Ms. Monica Wu

Organizing Committee of WCV-2017 Singapore

East Area, F11, Building 1,

Dalian Ascendas IT Park,

1 Hui Xian Yuan,

Dalian Hi-tech Industrial Zone,

LN 116025, China

Tel: 0086-411- 84799609 EXT 834

Email: monica@vaccinecon.com

From: (6) Genomics 2018 [mailto:genomics@annualconferences.org]

Sent: Friday, July 28, 2017 2:07 PM

To: Shih-Jiun Yin (Paul Yin)

Subject: Re:Globalize your Research by Speaking at Genomics 2018

Importance: High

Dear Dr. Shih Jiun Yin,

Greetings from Genomics2018!!

We solicit your gracious presence at 10th International Conference on Genomics & Molecular Biology, May 21-23, 2018 Barcelona, Spain on theme “Advanced Approaches In Genomics and Molecular Biology”

For more details please visit: http://genomics.conferenceseries.com/

Kindly acknowledge the mail and reply us with your interest to join the conference.

Regards

Kristina Smith

From: (7) Clinical Gastro 2017 [mailto:clinicalgastro@gastroenterologysociety.com]

Sent: Monday, August 21, 2017 2:54 PM

To: Shih-Jiun Yin (Paul Yin)

Subject: Honorable Speaker Invitation - Clinical Gastro 2017 | Madrid | Spain

Importance: High

Dear Dr. Shih-Jiun Yin,

The purpose of this letter is to welcome you, to be a speaker at the upcoming 13th International Conference on Clinical Gastroenterology and Hepatology ( Clinical Gastro 2017) on December 07-08, 2017 at Madrid , Spain a leading forum for Directors, CEO’s of Organizations, Association presidents, Associate Professors, Assistant Professors, Graduates, Post Graduates and PhD Scholars in Gastroenterology and digestive diseases.

Gastro 2017 will focus on “Recent advancements and therapeutic techniques in the field of gastroenterology” which covers a wide range of critically important sessions from basic research to innovations in the area of gastroenterology diseases and other metabolic syndromes.

Based on your interest in the related field, submit you’re abstract at http://gastro.cmesociety.com/abstract-submission

Accepted abstracts will be published with DOI

20 minutes Speaker talk slot

Group registration for more than 3 members

International Speaker recognition

Speaker profile in Google under your name will attract 35K researchers across the globe

We would like to know your availability and interest to deliver a Speaker talk at the respective sessions to be conducted at the conference venue.

We welcome your interest, questions, and comments.

Regards

Alexander Lee

Program Director - Clinical Gastro 2017

Gastroenterology Conferences

T 650 268 9744 | M 702 508 5202 (USA)

E clinicalgastro@gastroenterolgysociety.com

From: (8) Biofuels-2017 [mailto:biofuels@conferencescanada.org]

Sent: Friday, September 08, 2017 12:24 AM

To: Shih-Jiun Yin (Paul Yin)

Subject: RE: Invitation to be an honorable speaker

Importance: High

Dear Dr. Shih-Jiun Yin,

Greetings!

We sent you an email regarding the Speaker invitation for Biofuels -2017. But we didn’t get any response from your side because of your busy schedule. This is a follow up mail, so kindly let us know your opinion regarding the same. We hope that you will honor us by accepting our invitation.

The purpose of this letter is to formally invite you, on behalf of the Organizing Committee, to be a honorable speaker at the upcoming "7th International congress on Biofuels and Bioenergy" (Biofuels-2017) on October 2-4, 2017. This conference will be held at Toronto, Canada with the theme “Exploring the Advancements in the Field of Biofuels & Bioenergy”.

With a long tradition in welcoming people from all over the world, "Toronto", the host city, is among the most coveted tourist destination, and hence the perfect place to hold such event. This event designed for the International professionals to facilitate the dissemination and application of research findings related to Biofuels and Bioenergy as replacement fuels. In this regard, it will provide a key networking and an educational interface for academic colleagues, industries and independent research organizations around the world.

For more details, please visit: Biofuels-2017 website

The scientific events planned by the organizing committee will make this conference a memorable international event that will undoubtedly thrill you and satisfy your curiosity.

Thank you for your time and looking forward to see you at Toronto, Canada.

Regards,

Christopher Eccleston

Biofuels- 2017 organizing committee

From: (9) Metabolomics-2018 [mailto:metabolomics@scientificfederation.org]

Sent: Monday, September 18, 2017 1:03 PM

To: Shih-Jiun Yin (Paul Yin)

Subject: Honorable Speaker invitation at Metabolomics, USA

Importance: High

Global Summit on Metabolomics

(July 16-17, 2018 at Miami, USA)

Dear Dr. Shih-JiunYin,

Greetings from Metabolomics 2018!!!

On behalf of the Organizing committee, we have delighted in inviting you to solicit your presence as a speaker at the “Global Summit on Metabolomics” on July 16-17, 2018, which will be held in Miami, USA.

Metabolomics - 2018 will focus on the theme “To Develop and Explore Advanced Research in Metabolomics".

Metabolomics -2018 will provide the excellent opportunity to meet experts, exchange information, and strengthen the collaboration among Directors, Researchers, Associate Professors, and Scholars from both academia and industry.

Please have a glance at PS: http://www.scientificfederation.com/metabolomics-2018/

Benefits:

Ø All the accepted abstracts will be published in the Conference book

Ø International Certificate

Ø Meet the experts related field

We really like to have your presence at this conference. please let me know your interest towards the same. We will also cordially invite a large group of researchers to join the conference and share their research related to Metabolomics. We confident that participants will benefit from the high value scientific program.

Looking forward to join us in Miami, USA…!!!

Awaiting your swift and favorable response

Best Regards,

Vidyadhari

Organizing Committee Assistant Metabolomics 2018

T: +91-779-979-0001

Medical Conferences

Conference Manager

Email: metabolomics@scientificfederation.com

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