Kyosuke Nagata President University of Tsukuba

Dear Colleagues and Friends

It is my distinct pleasure to welcome everyone to Tsukuba Global Science Week (TGSW) 2015, now for the 6th year running.

The history of the University of Tsukuba extends back 143 years when it was founded by the Meiji government as Japan’s fi rst institution of higher education and premier Normal School. A little over forty years ago in October 1973, our university was relocated from Tokyo to Tsukuba City where it was reborn as a comprehensive institution of higher education.

Since its establishment, the University of Tsukuba has aimed for interdisciplinary education and research and to be a university open to society and the world. In accordance with these principles, we are delighted to host TGSW once again, which gathers together a number of participants not only from a diverse range of academic fi elds, but also from many different countries. What started out as an event with a single academic discipline, TGSW 2015 now offers sessions from a wide variety of fi elds ranging from hard sciences to humanities with prominent researchers from over 40 different countries.

One of the highlights of this year’s TGSW is a session on “Engagement in the Olympic and Paralympic Movement,” with keynote speech by Mr. Nick Fuller (IPC), along with presentations and discussions bearing on the future and legacies of the movement with contributions from representatives of the Special Needs Education School for the Physically Challenged, International Paralympic Committee, University of Bordeaux, and AISTS, among many others. The session is particularly fi tting for this occasion, not only because Tokyo has been chosen as the venue for the 2020 Olympic and Paralympic Games, but also because we are one of the world’s premier research institutes for sports science and sports medicine with over 60 Olympic medalists.

4 TGSW is a show case of world class researches carried out by our faculty members jointly with fellow scientists throughout the globe, including those associated with public and quasi- public institutions based in Tsukuba Science City and our partner universities outside Japan. But TGSW is more than that. The human race is now facing a range of global challenges – food crisis, energy issues, environmental risks, never-ending wars, poverty, and the list goes on. In order to proceed towards their solutions, the greater community of scientists, regardless of their areas of specialty, citizenship, ethnicity, gender, faith, and world views, must get together and collaborate closely. TGSW can serve as an invaluable forum for exchanging views on how to meet those challenges in a way that defi es all kinds of traditionally conceived barriers.

I would like to thank all of you for your participation and sincerely hope that you will enjoy this three-day event. I look forward to meeting with you during the week to further strengthen our ties for more cooperation.

5 6 0 Opening Session

Monday, September 28 Venue: Conference Room 300

Opening Session

This session is to kick-start Tsukuba Global Science Week 2015. Professor Atsushi Suzuki of Kyushu University’s Medical Institute of Bioregulation, who is one of the 11th (FY2014) JSPS PRIZE Awardees, will be the keynote speaker.

MC: Takeshi Hirose, University of Tsukuba Kyosuke Nagata University of Tsukuba 8:45-8:55 Opening Remarks Representative from CAO Cabinet Offi ce, Government of Japan 8:55-9:00 Ceremonial Address Ministry of Education, Culture, Representative from MEXT Sports, Science and Technology 9:00-9:05 - Japan Ceremonial Address Atsushi Suzuki Kyushu University 9:05-9:35 Keynote Address: A Challenge to Medical Innovation from Biological Aspects

9:35-9:55 Photo Session

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8 1 Human Scales and Subjectivities

Tuesday, September 29 Venue: Conference Room 304

Human Scales and Subjectivities

How can we assess the ways in which humans (i.e., concerned persons, bystanders, experts, activists, administrators, and politicians) conceptualize the problems of the world? In this session, we will present concrete cases ethnographically and discuss them in a cross-disciplinary way.

Session Organizers: Yasushi Uchiyamada and Shuhei Kimura Part One Chair: TBA, University of Tsukuba Yasushi Uchiyamada University of Tsukuba 9:00-9:10 Opening remarks Shuhei Kimura University of Tsukuba 9:10-9:50 On the scales to measure disaster reconstruction David Spraig NIAES 9:55-10:35 Trying to see the obvious: Measurement, categorization, and decision making based on human perceptions of natural variation Coffee break Valerie Olson University of California, Irvine 10:50-11:30 Subjects of the system: making humans to scale in U.S. environmental science and technology Discussion 11:35-12:00 Discussants: Toshihiro Kameda (University of Tsukuba), TBA Part Two Chair: TBA, University of Tsukuba Junko Teruyama University of Tsukuba 13:15-13:55 Speaking of how well I speak: personal evaluation of communication skills among autistic individuals Grant Jun Otsuki University of Tsukuba 14:00-14:40 The human as life or as communication Coffee break Gergely Mohácsi Osaka University 14:55-15:35 Pharmaceutical Gardens: On scaling life and anthropology through bioprospecting medicinal plants in Vietnam Yasushi Uchiayamada University of Tsukuba 15:40-16:20 Beyond perception of the world: Being in the world after the nuclear accident Discussion 16:25-16:50 Discussants: Ryosuke Ohniwa (University of Tsukuba), TBA

16:55-17:15 Roundtable

9 1-3

Subjects of the system: Making humans to scale in U.S. environmental science and technology

Valerie A. Olson

Department of Anthropology, University of California, Irvine

This paper uses anthropological fi eldwork in U.S. astronautics, marine ecosystem science, and terrestrial ecosystem science to examine the making of “systems subjectivity” at the levels of rhetoric, practice, and governance. Based on data from a total of ten years of ethnographic data collection within government research and development facilities, research institutions, and private companies, the paper examines how experts recast the human as a “system” or “subsystem” of larger environmental or ecological systems, thereby formalizing new authoritative forms of knowledge about human/environment interfaces, human/non- human relations, and ecosystem management across extreme scales. While social scientists continue to use and reject “systems thinking” and “systems theory” as analytic tools the past decades, there remains little ethnographic work specifi cally aimed at examining “system” as an historical and changing object of culture and practice. This leaves open the question of how contemporary experts in elite settings use the “system” concept in everyday technical, scientifi c, and political practices – including how experts perceive themselves and “the human” as systemic subjects. This paper treats “system” as an ethnographic object in order to track how it operates as a technology of relational and scalar ordering that takes on contingent, shared, and contested manifestations in particular social settings.

10 1-5

The human as life or as communication

Grant Jun Otsuki

University of Tsukuba

How might we view human beings differently if we suspend the assumption that humans are a form of life? In this paper, I present fi ndings from an ethnographic study of scientists and engineers in a fi eld I call “Human-Centered Technology” (HCT) in Japan who develop technologies to interface humans and machines. The objective of HCT is to create technologies that can make humans more comfortable, secure, and able to adapt to increasingly complex societies. I argue that these researchers do not assume that the human is a form of life, but a form of communication. I show how when these researchers suspend the assumption that “life” defi nes human existence, they become able to articulate the challenges that complex technologies pose to human society on different scales. This reveals to them new avenues for technologies to intervene in and improve human life. I support this argument with examples showing that (a) HCT researchers view the human as a system of communication, not a form of life; (b) when the assumption that human is life is reintroduced, the researchers reproduce a conservative vision of society that obscures the infl uence of social and political structures in human life, and (c) when they suspend the assumption of life, they imagine scales of human existence through which conservative visions of society may be challenged.

11 1-6

Pharmaceutical gardens: On scaling life and anthropology through bioprospecting medicinal plants in Vietnam

Gergely Mohácsi

Osaka University

While most of the “traditional” knowledge of medicinal plants in Vietnam and Japan derive from classic texts of Chinese medicine, their cultivation, preparation and prescription follow different scales—from herbal gardens in quasi-socialist cooperatives, to Japanese extracts or the universal human body of biochemistry—some of which do not necessarily nest neatly in each other. The alterity of Vietnamese and/or Chinese medical traditions, and scientifi c explanations depends on the the practices of scaling in which they deploy themselves: the industrial production of extracts that target global health problems; the micropropagation of engendered species in a laboratory; or the sampling of plants across the country. One site of these sampling activities that are the topic of this presentation is a garden—which is actually two gardens—in Đồng Nai province, east of Ho Chi Minh City in Southern Vietnam. Drawing on my fi eldwork with molecular biologists and a traditional Vietnamese doctor who cultivates the gardens, I will explore the methodological usefulness of scaling against the backdrop of recent debates on ontological multiplicities in anthropology and science studies.

12 1-7

Beyond perception of the world: Being in the world after the nuclear accident

Yasushi Uchiyamada

University of Tsukuba

The process of “reconstructions” in Fukushima is extremely slow as compared to those in the Sanriku coast to the north. The slowness of the process indicates the nature of the accident. The works of reconstruction and decontamination do not end the presence of radioactive materials in the environment. The imperceptible agents interact with living things and non- living things, and this makes the difference in kind: the difference in terms of the how of the world as well as the how of the subjectivity. The technique of knowing the world is no longer the same either: sievert, becquerel, cesium, strontium, for instance, have become part of the everyday lexicon and part of doing ordinary things. Does this mean that our perception of the changing environment have expanded and extended by the development of new technologies? I shall present an ethnographic case history of competing collectives of humans, equipments and categories in Fukushima to discuss the issue.

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14 2

Monday, September 28 Culture and Security: Exploring Future Values through Japanese Experiences Venue: Conference Room 303 Culture and Security: Exploring Future Values through Japanese Experiences

Culture brings both peace and confl ict. Sometimes it is the essential force that binds people together, but at other times, it tears them apart. When does culture bring peace among states or groups? When does it suddenly become a source of violence? Can our past experience help us create values that contribute to future peace and stability? What roles does Japan play in encouraging peace? We seek to gather scholars of varying research backgrounds and spark discussions that may answer those questions and other questions that may spring from the open-ended discussions.

Session Organizer: Yutaka Tsujinaka

Chairs: Joji Kijima and Takafumi Ohtomo, University of Tsukuba Yutaka Tsujinaka University of Tsukuba 14:15-14:20 Opening Remarks Akira Tsuneki University of Tsukuba 14:20-14:35 The Role of Cultural Heritage and its Current Condition in Iraq and Syria Youssef Kanjou JSPS Fellow, University of Tsukuba 14:35-14:50 Cultural Heritage, Identity and Confl ict in the Middle East: Causes and Future Rebuilding David Leheny Princeton University 14:50-15:05 Culture through Security Politics: Technocracy, Knowledge, and Rationality in the US-Japan Security Debates Verena Blechinger-Talcott Freie Universität Berlin 15:05-15:20 Making the Alliance Work: Academic Exchange Programs, U.S.-Japan Relations, and Japanese Security Chih-yu Shih National Taiwan University 15:20-15:35 Post-Chineseness and Mainlandaization Michel Brousse University of Bordeaux 15:35-15:50 Education and Sport: Judo and the Social Control of Violence 15:50-16:00 Break Discussants Comments Irmela Hijiya-Kirschnereit Freie Universität Berlin 16:00-16:45 Naoki Murata Kodokan Yutaka Tsujinaka University of Tsukuba Saburo Aoki University of Tsukuba 16:45-17:15 Discussion, Q&As from the fl oor

15 2-1

The role of cultural heritage and its current condition in Iraq and Syria

Akira Tsuneki

Professor, University of Tsukuba

Cultural heritage has played an important role in the integration of human groups throughout history. It becomes the evidence of oppressed peoples’ survival and sometimes encourages them to rebel against external political pressure. In some cases, it becomes the primary evidence for a particular race and is used as a weapon to attack others. Cultural heritage can be used as an implement to revive or kill particular human groups. This is the reason why people conversely guard and destroy it during times of confl ict. Modern Iraq and Syria form the heartland of ancient Mesopotamian civilization. Many great human innovations were developed in this region, and it provided the foundation for all modern civilizations. Because of this, the cultural heritage in these two countries is extremely important not only for their own national histories but also for the entire human history. However, they are now faced with the threat of destruction given present severe political conditions. Cultural heritage has been destroyed in the confl icts between regimes and anti-regimes. Lack of authority has overlooked illegal digging and the hemorrhage of cultural property. Some important objects have been stolen even from national museums. In addition to such tragic occurrences, the religious destruction of some cultural heritage by IS is a recent addition. I introduce the current condition of cultural heritage in Iraq and Syria. Later, I will discuss not only what we can do to protect their cultural heritage, but also how we can use such activities for mutual understanding and security.

16 2-2

Cultural heritage, identity and confl ict in the Middle East: Causes and future rebuilding

Youssef Kanjou

JSPS Fellow at the Tsukuba of University & Former Director of the National Museum, Aleppo

The area of the Middle East has a long history and large number of archaeological sites which tell us important aspects about the development of human civilization, from the origin of agriculture, animal domestication to the invention of the alphabet and writing. The variety of ethnicities and cultures in this region is one of its most notable aspects from the distant past and until the present, which manifests nowadays in religion and language in daily life in many regions. The current situation in the Middle East started with the “spring revolution”, and as a consequence of complicated confl ictaffected all aspects of human life. Many people were killed and millions displaced from their homes and fl ed to neighboring countries. Later the war cut away the roots and connections of people to the land which had existed for thousands of years. This happened when the war (military and extremist) started to destroy the cultu ral heritage of the nations in direct ways such as the destruction of the old city in Aleppo, Syria (world heritage site 1984) and the Mosul museum in Iraq. In this presentation, I try to explain the reasons for the destruction of this cultural heritage, the efforts of communities and local authorities to protect their national heritage, how we can protect cultural heritage in future, and the role that museums can play to reinforce identity and the peace process.

17 2-3

Culture through security politics: Technocracy, knowledge, and rationality in the US-Japan security debates

David Leheny

Henry Wendt III ’55 Professor of East Asian Studies, Princeton University

One of the risks of discussing culture and security is the tendency to depict either as a stable entity. After all, security is inherently a moving target, given the myriad ways in which one might imagine threats and what it might mean to be secure from them. And yet we depict security as a goal that might somehow be achieved. Similarly, culture is frequently described as a national thing — Japanese culture, American culture, French culture, etc. — despite the obvious fact that all of these nations change over time, and the people within them are too diverse and complex to capture with the label of national culture. In this presentation, I focus on the ways in which security debates become opportunities to build and articulate ideas about national cultures, focusing especially on revisions to Japanese security policy over the past fi ve years. I address, on the American side, how pressure on Japan to develop a more proactive military stance was depicted as the obvious step a major country should be willing to take. On the Japanese side, I focus on the orientation of the security law debate around constitutional issues. My goal is not to argue what Japan should or should not do, but rather to show how debates about security become an opportunity to articulate claims about culture. In this sense, my presentation will be less about culture itself than the use of a cultural perspective to interrogate political debate.

18 2-4

Making the alliance work: Academic exchange programs, U.S.-Japan relations, and Japanese security

Verena Blechinger-Talcott

Professor of Japanese Politics and Political Economy, Freie Universität Berlin

The United States are Japan’s key partner in security and economic relations. To stabilize and strengthen the alliance and to generate goodwill among citizens, both states use, among others, cultural diplomacy as a means to increase mutual understanding of core values, ideas, and principles. Academic exchange programs are an important instrument of cultural diplomacy, since the scholars and students involved often have an impact on elite perception and training as well as on agenda setting in politics and academia. This presentation addresses the impact of cultural diplomacy, and especially of academic networks on U.S. – Japan relations. It analyzes the goals, principles, and scope of the most prominent academic exchange programs between the U.S. and Japan and follows the career paths of former participants. The project aims at evaluating the effect of academic exchange programs and resulting Japanese-American academic networks on agenda setting in Japanese political science and elite perception of the alliance.

19 2-5

Post-Chineseness and Mainlandization

Chih-yu Shih

Professor, Department of Political Science, National Taiwan University

“Post” in post-Chineseness alludes to a temporal concept in which Chineseness is a layered characteristic, which is at least once active, ready for recollection, constantly revisable, strategically instrumental, and occasionally inspirational. Chineseness accordingly involves processes of mutual recognition via shared cultural resources, in use as well as in memory. Every two Chinese groups may share a peculiar understanding of the Chinese culture or history. The capacity and the process to incur resources in the shared cultural repertoire compose the mechanism of Chinese relationality. Mainlandization therefore triggers particular processes of Chinese relationality. It is the incurring of shared Chinese cultural resources to facilitate recovery (of lost territory), expansion (of Communist-Party infl uence), assimilation (of formerly colonized population), reunifi cation (of split regimes), integration (of alienated ethnicity), submission (of a dissident group), networking (of diasporic population), return (of a migrant cohort) and so on, in order to enhance Chinese relationality of the targeted group, site, and sector anywhere, those territorially proximate ones above all. The initiatives of Mainlandization may come from all sources, hegemonic as well as subaltern, domestic as well as overseas, offi cial as well as private, and political as well as psychological. The merit of post-Chineseness as a theme is precisely that it acknowledges that the material strength of China accelerates the incurring and invention of shared cultural resources and yet, on the other hand, it shows that the intensity and sophistication of evolving relationality uncontrolled by the political center of territorial China reinforce post-Chineseness rather than undermine it.

20 2-6

Education and sport : Judo and the social control of violence

Michel Brousse

Professor, University of Bordeaux

In today’s socio-political context where insecurity is presented as a crucial issue and a recurrent problem, sport culture is currently viewed as one of the few instruments that might help solve the problems and pacify the social climate. It is seen as a unifying factor and a prior- ity vector in order to convey humanistic values. Sports offer uncountable examples of sharing out, of solidarity, friendship and reunifi cation. At the same time it is not free from excesses. Since Norbert Elias’ essays the evolution of sport activities analyzed through the prism of their organizations and governing rules has often been considered as illustrative of the control of social violence. But socialising people through sport does not prevent manifestations of “wild” violence. This presentation intends to show how the social control of aggressive behaviour needs a complex set of measures. Bordeaux and its region, classifi ed as a UNESCO World heritage site, offer several programs using sport as a factor of integration and a tool to prevent youth delinquency. Among them, judo stands out as a good example to demonstrate how the power of sport and its culture essentially rest on the values that are taught and on the teach- ing process itself. Jigoro Kano’s ambition to bring educated and responsible citizens into the modern world clashes with the approach and politics of those who only strive for sports results. The quest for immediate performances defi nitely contradicts the original educative stance. The outcome being acts of violence that paradoxically lead the general public to associate an image of insecurity with a discipline that has essentially been conceived in order to improve individuals for the good of society. I will offer a comparison between French and Japanese judo to point out the elements deemed to be essential to the contribution of sport culture to security, social responsibility and social peace.

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22 3 Cross-cultural and Cross-religious Encounters in Historical Context

Tuesday, September 29 Venue: Conference Room 404

Cross-cultural and Cross-religious Encounters in Historical Context

This session comprises two parts, the morning session, organized by scholars of Ethics and Western Philosophy, mainly brings to light the early-modern evangelical activities of the Jesuit Order in East Asia, while the scholars from Indology and Buddhist Studies organize the afternoon session concerning the religio-philosophical perspective in cultural diversity in pre-modern India.

Session Organizers: Taisei Shida, Chizuko Yoshimizu, and Naoki Kuwabara Part One Chair: Naoki Kuwabara, University of Tsukuba Kenichi Nejime Professor, Gakushuin Women’s College 9:10-9:40 The Japan’s Christian Century and the Italian Renaissance: From the Point of View of the Immortality of the Soul Yoshitsugu Igawa Professor, University of Tsukuba The Understanding of the Soul Theory in China by the Jesuits of the 17th Century : 9:40-10:10 Mainly on Translation of The Doctrine of the Mean (『中庸』) in Confucius Sinarum Philosophus Patrick Schwemmer Sophia University / Princeton University 10:10-10:40 A Bicultural, Bilingual Theatrical Exchange between the Tenshō Boys’ Embassy and the Kyūshū Collegio Noriaki Takaishi Doctoral Candidate, University of Tsukuba 10:40-11:10 Intellect and Will: A Comparative Study of Thomas Aquinas and Pedro Gomez Ryuta Ishida Doctoral Candidate, University of Tsukuba 11:10-11:40 How to Use the Writings of Saint Thomas Aquinas: On Pedro Gómez’s Compendium, Part 2 11:40-12:00 Comments and Floor Discussion Part Two Chair: Ernest Brewster, Harvard University Akihiko Akamatsu Professor, Kyoto University 13:20-13:50 Doxography and Perspectivism in Pre-Modern India Taisei Shida Associate Professor, University of Tsukuba 13:50-14:20 The Exegetic School’s Dialogical Strategy for the Authorization of Scripture in Classical India Harunaga Isaacson Professor, Hamburg University / University of Tsukuba 14:20-14:50 Verses by Buddhist Authors and Verses with Allusions to Buddhism in Two Post-1200 AD Anthologies of Sanskrit Verses Alexis Sanderson Professor, Oxford University 14:50-15:20 The Tantric Rebirth of Indian Buddhism under Śākta-Śaiva Infl uence during the 7th to 11th Centuries 15:40-16:10 Comments and Floor Discussion

23 3-1

The Japan’s Christian Century and the Italian Renaissance: From t he Point of View of the Immortality of the Soul

Kenichi Nejime

Gakushuin Women’s College, Tokyo

Christianity was introduced in Japan by the Jesuit Francis Xavier, a graduate of Paris, in 1549. This marked the beginning of its Christian era, which lasted until the mid-seventeenth century. Xavier and his followers did not only bring the doctrines of the Catholic Church to the country. They also brought the customs and culture of the West. Its major intellectual compo- nents of the time were three kinds, traditonal Aristotelianism, two new trends, both humanism and Platonism. The introduction of humanism and the revival of Platonism, which began in Florence and other Italian cities, are known to have exerted a considerable impact on European culture. Upon his arrival, Xavier was struck to learn that the local Buddhist monks denied the possibility of life after death. For his evangelical activity, Xavier opted to emphasize the doctrine of the immortality of the soul. The Jesuits who followed him continued to work in this direction. The doctrine has had profound relation to the theory of the Platonism. And then it was determined for the fi rst time as the article of faith at the Fifth Lateran Council (1513). Several important studies have shown that Europe saw lively debates on the doctrine of the im- mortality of the soul among religious orders and leading philosophers during the Renaissance. Disputes on the same issue between the Jesuits and the Japanese Buddhists show a striking parallel. Thirty years after Xavier, another Jesuit and a law graduate of Padua, Alessandro Valignano, came to Japan and founded a Jesuit college where the studia humanitatis would be taught to local students. Here Valignano, as a Renaissance man, knew the importance of the humanism as well as of the Aristotelianism and of the Platonisim. This paper will thus address the religious and cultural encounters between the West and Japan in the early Modern Age.

24 3-2

The Understanding of the Soul Theory in China by the Jesuits of the 17th Century: Mainly on Translation of The Doctrine of the Mean (『中庸』) in Confucius Sinarum Philosophus

Yoshitsug u Igawa

Doctoral Program in Philosophy, Graduate School of Humanities and Social Sciences, University of Tsukuba

Chinese study book Confucius Sinarum Philosophus (1687), that received the publication support from Louis 14th, introduced the fi rst philosophical information on the soul of China to Europe. Authors, Philip Couplet and Prospero Intorcetta believed that there was affi nity between Chinese philosophy and the Christian doctrine. They depended on cultural accommodation policy of Matteo Ricci and profoundly studied Chinese classics. In addition, they chose the commentaries which supported their opinions carefully. Missionaries widely adopted his interpretation for understanding and the translation of the classical Chinese original texts, though they criticized the commentary of Zhu Xi (朱熹) who rationalized excessively to explain everything. They recommended a commentary of Zhang Ju-zheng (張居正), who was in a leadership position in politics and education, as favorable interpretation. It was because the peculiar role of the divinity and the spiritual entia was found by Zhang Ju-zheng's commentary. Missionaries' understanding about the spiritual entia indicated on a classic of Confucianism, The Doctrine of the Mean is examined in this presentation. They insisted that the Chinese representative documents had concepts similar to spiritual entia in Christianity. It seems that missionaries tried to explain through such information the results of the China propagation, and to insist China could be Christianized. On the other hand, there is a thought frame concerning the correlation between the universe and human being, everything and human being which assume Ratio (Li, 理) intermediation in The Doctrine of the Mean (Zhongyong,『中庸』). Such worldview is going to be introduced to Europe at the same time through translation. The Chinese soul theory was introduced with a background of such a cosmology. There might have been a person who had paid attention to such a cosmology in the readers. I collate and examine the fact of such an information with the classical Chinese original texts, various commentaries, and Latin translations.

25 3-3

A Bicultural, Bilingual Theatrical Exchange between the Tenshō Boys’ Embassy and the Kyūshū Collegio

Patrick Schwemmer

Dep artment of Japanese Literature, Sophia University

The Jesuit order is well known for its educational use of theatre and other performing arts, and its activities in sixteenth-century Japan were no exception. However, Japanese Jesuit theatre underwent various changes over the course of the sixteenth century in response to pressures both internal and external. In the fi rst twenty years of the mission (ca. 1550–1570), everyday parishioners of the churches of Kyūshū were encouraged to produce and perform songs, dances, and plays based on biblical and other legends, and the ceremonial presentation of such pieces before local lords was an important part of the Jesuit strategy to accomplish and then reward their conversions to Christianity. However, the 1570s saw growing opposition to the use of performing arts in a missionary context, and when the new Visitor Valignano arrived in Japan in 1579, an offi cial statement from the Superior General in Rome all but prohibited performances involving lay brothers, in Japanese, or in churches. However, although Valignano and his subordinates at least stop reporting local performances of Christian drama, they nevertheless make musical, choral, and dramatic instruction in Latin a focus in education of young Japanese in the new Collegio. Meanwhile, Valignano himself was busy parading four such youths around Europe, where, in addition to meeting kings and popes, they studied European instrumental and choral music and took part in ceremonial plays dramatizing their own journey in the context of world history as the Jesuits conceived it. Thus, in 1590, upon the young ambassadors’ return to Japan, the stage was set for an exchange of concerts, plays, and dances, sponsored by Arima Harunobu, between the ambassadors and the students of the Collegio who had been studying the same arts in Kyūshū. In this presentation, I introduce this event from previously-undiscussed original documents.

26 3-4

Intellect and Will: A Comparative Study of Thomas Aquinas and Pedro Gomez

Noriaki Takaishi

The purpose of this presentation is to compare the thinking of Saint Thomas Aquinas, the 13th century theologian, and Pedro Gomez, a 16th century Jesuit, on intellect and will. The ethical thinking of Gomez is based on that of Aquinas, but there are not a few differences between them. One of the differences is their ideas about which is more primary for human acts, intellect or will. This question has been discussed by many thinkers for a long time. Aquinas counts generally among intellectualists. This understanding is incorrect inasmuch as the cardinal element of his thinking is love, which is an activity of will. But he is indeed an intellectualist in that he is quite different from the voluntarists, who rose to prominence after him. On the other hand, a voluntarist tendency is found in the thinking of Gomez. He lays stress on the power of the will where Aquinas instead focuses on the activity of the intellect. Generally speaking, Gomez is not a voluntarist. However, compared with Aquinas, he can be called one. Since Gomez discusses human acts in more or less the same way as Aquinas, their thinking is easy to compare. Therefore, I will inquire into the intellect and will behind human acts by comparing these thinkers.

27 3-5

How to Use the Writings of Saint Thomas Aquinas: On Pedro Gómez’s Compendium, Part 2

Ryuta Ishida

Doctoral Program in Philosophy, Graduate School of Humanities and Social Sciences, University of Tsukuba / Japan Society for the Promotion of Science

In Ratio studiorum (fi rst drafted in 1586 and completed in 1599), the teachings of Saint Thomas Aquinas (c.1224―74) are regarded as one of the most important curriculums in Jesuit schools. His Summa theologiae is one of the main texts used for teaching activities. In particular, there is a detailed plan to teach Summa at each grade in The Rules for Professors of Scholastic Theology (Regulae professoris scholasticae theologiae) of the 1599 version of Ratio. However, 1599 Ratio explicitly designates the Summa only as a work for use in education, and does not nominate any other writings of Aquinas as educational resources. By turning our eyes to Pedro Gómez’s Compendium, written in 1593, and probably the fi rst substantial textbook used for theology studies at the Jesuit Collegio in early modern Japan, we might notice a difference between the 1599 Ratio and Compendium. The Compendium also uses the doctrine of Thomas Aquinas as one of the most important sources from which students ought to learn. However, Part 2 of Compendium lists explicitly many other writings of Thomas Aquinas than Summa theologiae. The list includes Summa cont ra gentiles (another major work of Aquinas), Quaestiones disputatae de potentia Dei (a record of the disputed questions on the theme of the power of God), and one opuscule. Contrasting this with the 1599 Ratio, there is a variety of writings by Aquinas included, but why? By answering this question, my presentation will seek to evaluate the infl uence of the thought of Thomas Aquinas on Gómez’s Compendium, Part 2, referring to every work by Aquinas used in Compendium. This will also provide us with one example of the use of the writings of Aquinas in the educational fi eld.

28 3-6

Doxography and Perspectivism in Pre-Modern India

Akihiko Akamatsu

Department of Indological Studies, Graduate School of Letters, Kyoto University

Here, I am to bring to light the refl ective consciousness held by the people of pre-modern India towards their own perspectives. When Aristotle spoke in Metaphysics about ‘those who fi rst formed the systems of philosophy’, he was speaking of the beginnings of philosophy, and simultaneously, his discussion of these beginnings can itself be said to be the self-conscious beginning of academic ‘philosophy’. Therefore, it can be said that a philosophy that was directly linked with consciousness of a beginning was particularly recognized by the Greeks as a specifi c type of self-consciousness and a form of self-knowledge. If philosophy by this defi nition was, to the Greeks, the form of a particular knowledge, then it should be possible to treat the unique Indian argumentative style—one that relativizes its own perspective, despite lacking (or simply without having) a privileged consciousness of ‘beginning’—as a view on things unique to pre-modern India. Texts in this style bequeathed to us are by necessity introduced here as ‘doxographies’, although the term may be thought of as somewhat strange. If ‘historiography of philosophy’ is a genealogical description of the historical development of doctrines, as in Aristotle’s description of philosophy from its beginnings to Plato in Book I of Metaphysics, then ‘doxography’ is an approach that shows almost no interest in the historical spread and development of doctrines, but instead treats the doctrines of each school as closed, ahistorical systems and attempts to fi nd a place for them amid contrasts between ways of thinking and viewpoints held by other parties. I aim fi rst to introduce representative examples of such doxographies and to clarify the unique perspectives found within them. Then, I take up perspectives concerned with neutrality, paying special attention to perspectivism in Jainism as the background of the formation of such perspectives, and make use of the texts of Maillavādin (6th century) and of Yaśovijaya (17th century) to clarify these perspectives’ special characteristics.

29 3-7

The Exegetic School’s Dialogical Strategy for the Authorization of Scripture in Classical India

Taisei Shida

Institute for Comparative Research in Human and Social Sciences, University of Tsukuba

Among diverse religio-philosophical traditions in classical India, almost all the schools each have their own scripture as a religious and social norm, and they authorize the validity of their scriptures in various ways. The school of logic (Nyāya), like the Buddhist logico- epistemic school, appeals to the omniscience and the integrity of the assumed author of their scriptures, such as God or Buddha, despite the risk of circular or regressive logical problems in the process of justifi cation. Other schools authorize scripture by means of a negative assessment of human reasoning and experience. The Vedanta school, an extreme example, claims that what is revealed in the Veda is not to be verifi ed but merely to be accepted, and that this acceptance is itself a gift of the Veda. One of the most conservative Brahmanical schools is Mīmāṃsā, whose main concern is the exegesis of the scriptures, i.e., the Veda. Mīmāṃsā uses an idiosyncratic strategy for the authorization of the Veda, claiming the eternality of each phoneme as a medium of verbal communication, as well as the non-artifactuality (i.e. authorlessness) of words and sentences which constitute the scriptures. This authorization is also based on another theory peculiar to the school: the “intrinsic validity” of any cognition or sentence. This presentation aims to show how and why these notions, such as the eternality of phonemes, the non-artifactuality of words and sentences, and intrinsic validity, support each other and converge in the authorization of the Veda. In particular, I will investigate the rationality of the argumentation and its applicability to trans-national societies outside an Indian context, focusing on how each Mīmāṃsā apologist selects interlocutors and constructs a dialogical philosophical treatise.

30 3-8

Verses by Buddhist Authors and Verses with Allusions to Buddhism in Two Post-1200 AD Anthologies of Sanskrit Verses

Harunaga Isaacson1,2

1University of Hamburg, 2University of Tsukuba

As a small contribution to the session “Cross-cultural and Cross-religious Encounters in Historical Context”, I shall survey Buddhist material and allusions to Buddhism in verses in two post-1200 AD anthologies of Sanskrit verses: the Sūktimuktāvalī compiled by Jalhaṇa in 1258 at the Yādava court in the Deccan, and the Subhāṣitāvalī compiled by a Vallabhadeva in Kashmir, dating (at least in the form available today) probably to the 15th century. Apart from an overview of the material it will be considered what light it sheds on the level of ‘popular’ (among Sanskrit readers at least) knowledge of Buddhist literature and Buddhist thought in a period after organized Buddhism had entirely or almost entirely disappeared in the regions concerned.

31 3-9

The Tantric Rebirth of Indian Buddhism under Śākta-Śaiva Infl uence during the 7th to 11th Centuries

Alexis Sanderson

Spalding Professor of Eastern Religions and Ethics, University of Oxford, and Fellow of All Souls College, Oxford

In this paper I shall show how Tantric Buddhism developed by absorbing and adapting Śākta-Śaiva ritual methods, Yogic physiology, and post-initiatory ascetic practices. I shall consider the extent to which these fundamental changes should be seen as Buddhism’s having lost its ability to resist assimilation by the dominant religious idioms of the age and the extent to which the same may be understood as the product of a conscious strategy of recruiting and converting outsiders by adapting and subverting the latters’ non-Buddhist religious culture for Buddhist purposes. It will be concluded that there is no single simple answer to the question of how this profound change from the pre-Tantric Mahāyāna to its Tantric forms occurred. I will show that the development is far from being a steady progression, there being marked ups- and-downs that show the inadequacy of a single explanation in terms of permeability through weakness on the one hand and skillful manipulation for Buddhist purposes on the other; and I shall attempt to account for this unsteady trajectory, at least in part, in terms of the ebb and fl ow of the power of the state during the period under review. Finally, I shall propose that whatever the varied conditions under which esoteric Buddhism emerged and developed in India the whole process should be seen not as Buddhism in decline but as Buddhism undergoing a profound re-invigoration, one that empowered its successful transmission into inner Asia, China, Japan, and Southeast Asia.

32 4 Universe Evolution and Matter Origin

Wednesday, September 30 Venue: Convention Hall 300

Universe Evolution and Matter Origin

Research in the fi elds of elementary particles, nuclear physics, and astrophysics is being conducted at the Center for Integrated Research in Fundamental Science and Engineering (CiRfSE), with the aim of understanding them from a unifi ed view of the history of the universe. We review recent developments and discuss prospects in the near future.

Session Organizer: Fumihiko Ukegawa

Session 4 / 5 Universe Evolution and Matter Origin / Research Frontier of Developing Energy and Environmental-friendly Materials Chair: Fumihiko Ukegawa, University of Tsukuba Director, Center for Integrated Research Kazuyuki Kanaya in Fundamental Science and Engineering, 9:00-9:10 University of Tsukuba Opening Address and Introduction to CiRfSE Guillaume Unal CERN, Switzerland 9:10-9:45 Studies of the Higgs boson at the LHC Chair: Eiji Nishibori, University of Tsukuba Center for Materials Crystallography (CMC), Bo Iversen 9:45-10:20 Aarhus University Watching nanocrystals form 10:20-10:45 Break Chair: ShinIchi Esumi, University of Tsukuba Roy Lacey State University of New York at Stony Brook 10:45-11:20 Particle correlation studies in RHIC-BES; Probes for the critical end point in the QCD phase diagram Chair: Junji Nakamura, University of Tsukuba National Synchrotron Radiation Laboratory, Junfa Zhu University of Science and Technology of China 11:20-11:55 Applications of synchrotron radiation soft X-ray spectroscopies in the studies of energy-related functional materials 11:55-13:00 Lunch (3F Convention Hall 300) Session 4: Universe Evolution and Matter Origin (3F Convention Hall 300) Chair: Koji Sato, University of Tsukuba Leonardo Bronfman University of Chile 13:00-13:35 (Sub)mm-wave galactic astronomy in Chile: an historical perspective

33 SooBong Kim Seoul National University 13:35-14:10 Tentative: neutrino physics Hideki Okawa University of Tsukuba 14:10-14:35 Searches for diboson resonances at the LHC-ATLAS Experiment Oliver Busch University of Tsukuba 14:35-15:00 Exploring the QGP with jets with ALICE 15:00-15:30 Break Chair: Tatsuya Chujo, University of Tsukuba Yaxian Mao Central China Normal University 15:30-16:05 Hard probes at LHC Yuji Takeuchi University of Tsukuba Development of far-infrared single-photon spectrometers based on 16:05-16:30 superconducting tunnel junction for search for the cosmic background neutrino decaty Hiroshi Nakagomi University of Tsukuba 16:30-16:55 Flow and correlation results from RHIC-PHENIX experiment Nario Kuno University of Tsukuba 16:55-17:20 Antarctic 10-m Terahertz Telescope Project Coordinator, Research Core for the History of the Shinhong Kim 17:20-17:30 Universe, CiRfSE, University of Tsukuba Closing Remarks

34 4-3

(Sub)mm-wave galactic astronomy in Chile: A historical perspective

Leonardo Bronfman

Astronomy Department, Universidad de Chile

The fi rst dedicated southern hemisphere mm-wave telescope, the 1.2m SMWT, was installed in Chile in 1982. Molecular gas in the Galaxy was mapped with unprecedented coverage, through observations of the CO(1-0) transition at 115GHz, yielding the mass of molecular gas in the Galaxy, its ratio to atomic gas, and average radial distribution. Further studies reported the number and mass of giant molecular clouds (GMCs), and their tracing of Galactic spiral structure. Realization of the quality of the Chilean (sub)mm sky encouraged installation of the Swedish-ESO 15m SEST in 1987. With 12 times higher spatial resolution than SMWT, and frequency coverage up to 365 GHz, a main project was the identifi cation of the regions of massive star formation in the Galaxy, through observation of the CS(2-1) transition. Further mapping of their associated dust continuum emission allowed characterization of their size, mass, and luminosity. A U. Tokyo 60 cm telescope, operating during 1995-1997, mapped the CO(2-1) transition at 230GHz, to determine the temperature distribution of molecular gas. The Nagoya University 4m NANTEN telescope, since 1995, allowed mapping of several CO lines toward GMCs, measuring their densities; its relocation to higher altitude in 2005, and a new receiver built by U. Cologne permitted mapping of CI at 492 and 809 GHz. The NAOJ 10m ASTE (2002) and the Swedish-ESO 12m APEX (2005), at 5.000 m altitude in the Atacama plateau, have allowed detailed mapping, at frequencies up to 1.2 THz, of molecular gas and dust in GMCs, the back-bone of massive star formation in the Galaxy. The recent advent of ALMA, the largest (sub)mm-wave array interferometer on Earth, with hundredth of arcsec resolution, has allowed to study the intimate properties of Galactic star forming regions, to identify the physical mechanisms taking place in the all important process of star formation.

35 4-5

Searches for diboson resonances at the LHC-ATLAS experiment

Hideki Okawa on behalf of the ATLAS Collaboration

Division of Physics and Center for Integrated Research in Fundamental Science and Engineering (CiRfSE), Faculty of Pure and Applied Sciences, University of Tsukuba

The Large Hadron Collider (LHC) at the European Organization for Nuclear Research (CERN) has begun operation at the center-of-mass energy of 13 TeV (Run 2) in May 2015, yet again opening a new energy frontier. One of the historical achievements of the LHC at the center-of-mass energy of 7 and 8 TeV data taking (Run 1), was the discovery of the Higgs boson by the ATLAS and CMS experiments (ATLAS Collaboration, Phys. Lett. B 716: 1, 2012; CMS Collaboration, Phys. Lett. B 716: 30, 2012). Remaining questions are to understand the property of the Higgs sector in detail, and also to search for signs of physics beyond the Standard Model. Presence of diboson resonances is predicted by various extensions of the Standard Model. An extended scalar sector such as the two-Higgs-doublet model (2HDM) and the electroweak-singlet (EWS) model predicts additional Higgs bosons, which could decay to diboson, and motivates searches at higher masses than 125 GeV. Technicolor, warped extra dimension, and Grand Unifi ed Theories also predict diboson resonances. For scenarios with an extended scalar sector, searches for a heavy neutral scalar boson decaying into two Z bosons are considered, which have sensitivities in wide mass ranges. Searches with the llll, llvv, llqq, and vvqq decay modes are performed with 20.3 fb-1 of 8 TeV pp collision data (ATLAS Collaboration, arXiv:1507.05930, submitted to EPJC). No signifi cant excess of events over the Standard Model expectation is observed. The results are interpreted in the context of Type-I and Type-II 2HDM. Another series of searches are performed for diboson resonances using one or two hadronically-decaying W and Z bosons. An excess of events from the Standard Model prediction is observed in the two boson-tagged-jet channel around the invariant mass of 2 TeV with 20.3 fb-1 of 8 TeV pp collision data. The excess has a global signifi cance of 2.5 standard deviations (ATLAS Collaboration, arXiv:1506.00962, submitted to JHEP). Updated searches of diboson resonances are under way with the incoming 13 TeV data.

36 4-7 Hard probes at LHC

Yaxian Mao

Institute of Particle Physics, Central China Normal University

One of the signatures of the strongly interacting medium produced in heavy ion collisions is the suppression of high-transverse momentum fi nal state particles and jets. Jets and high pT particles, referred to as “hard probes”, provide experimental means to explore the details of parton-medium coupling and the energy loss mechanisms in QCD matter. To precisely understand the effect of the hot and dense medium produced in heavy-ion collisions on the production of jets and hadrons, initial-state effects such as the nuclear modifi cation of the parton distribution functions (nPDF) must also be understood. In this talk, an overview of recent jet and high pT measurements using the fi rst data taken at LHC will be presented, and the perspectives towards the new data analysis of LHC-RUN II especially within ALICE collaboration will be given.

37 4-8

Development of far-infrared single-photon spectrometers based on superconducting tunnel junction for search for the cosmic background neutrino decay

Yuji Takeuchi1, Shin Hong Kim1, Kenichi Takemasa1, Kenji Kiuchi1, Kazuki Nagata1, Kota Kasahara1, Kouya Moriuchi1, Ren Senzaki1, Shunpei Murakami1, Shunsuke Yagi1, Shuji Matsuura2, Hirokazu Ikeda3, Takehiko Wada3, Koichi Nagase3, Hirokazu Ishino4, Atsuko Kibayashi4, Satoru Mima5, Takuo Yoshida6, Ryuta Hirose6, Yoshiki Kato6, Chisa Asano6, Takahiro Nakamura6, Yukihiro Kato7, Yasuo Arai8, Masashi Hazumi8, Ikuo Kurachi8, Shigetomo Shiki9, Masahiro Ukibe9, Go Fujii9, Masataka Ohkubo9, Erik Ramberg10, Jonghee Yoo10, Mark Kozlovsky10, Paul Rubinov10, Dmitri Sergatskov10, Soo-Bong Kim11 and Shoji Kawahito12

1Institute of Physics, University of Tsukuba 2School of Science and Technology, Kwansei Gakuin University 3Institute of Space and Astronautical Science, JAXA 4Okayama University 5RIKEN 6University of Fukui 7Kinki University 8High Energy Accelerator Research Organization, KEK 9Advanced Industrial Science and Technology (AIST) 10Fermi National Accelerator Laboratory 11Seoul National University 12Research Institute of Electronics, Shizuoka University

We present a status of developments of far-infrared (FIR) single-photon spectrometers based on Superconducting Tunnel Junction (STJ), which we plan to apply to an experimental search for the decay of the cosmic neutrino background (CνB). The CνB is predicted to exist in standard cosmology, and the heaviest neutrino is expected to decay to lighter neutrinos with photons in the FIR region. Neither the CνB nor the neutrino decay is, however, experimentally established. We, thus, search for photons that come from neutrino decays in the CνB. The photon spectrum from the neutrino decays in the CνB is expected to have a sharp edge at high energy end around a wavelength of 50μm and a long tail in the longer wavelength side against the overwhelming zodiacal emission (ZE) foreground as well as cosmic infrared background (CIB). The detectors are required to measure the photon spectrum in the FIR region at 0.1% accuracy level to achieve a sensitivity in the order of 1014 years to the neutrino lifetime for a 200-second measurement with this rocket-borne detector. One of promising choices for the detector is a combination of a diffraction grating and an array of niobium-aluminum STJ (Nb/ Al-STJ) pixels, where each STJ pixel is capable of FIR single-photon detection delivered to each pixel according to its wavelength by the grating. Hafnium based STJ (Hf-STJ) which is expected to have less than 2% energy resolution for a FIR single-photon of 50μm thanks to very small superconducting gap energy of hafnium. Both the FIR single-photon detection with Nb/Al-STJ and the establishment of Hf-STJ as a practical FIR photon detector are highly challenging yet worthwhile.

38 4-10

Antarctic 10-m Terahertz Telescope Project

Nario Kuno1, Naomasa Nakai1, Masumichi Seta2, Tom Nitta1, Makoto Nagai1, Hiroaki Imada1, Yutaro Sekimoto3, Kazuo Sorai4 and Antarctic astronomy consortium

1Faculty of Pure and Applied Sciences, University of Tsukuba 2Kwansei Gakuin University 3National Astronomical Observatory of Japan 4Hokkaido University

The plateau of Antarctica is the best place for astronomical observations on Earth, especially for observations at infrared to submillimeter wavelengths. The temperature is quite low (e.g., -20°C~-80°C at Dome Fuji Station). The precipitable water vapor is also very low and lower than at any other sites of astronomical observatories on the ground. Furthermore, snow precipitation is very low and wind is not strong. We are planning to construct a 10-m class terahertz telescope at the altitude of > 3000m in the plateau of Antarctica. We will install a radio camera with wide fi eld of view on the telescope. Our main scientifi c aim is to make large fi eld surveys to fi nd extremely distant galaxies which emit most radiation energy via dust thermal emission at infrared to submillimeter. The data will provide invaluable information to understand galaxy evolution.

39 NOTE

40 5 Research Frontier of Developing Energy and Environmental-friendly Materials

Wednesday, September 30 Venue: Convention Hall 300/Conference Room 405 Research Frontier of Developing Energy and Environmental-friendly Materials

The topics in this section are focused on recent progress in a variety of fi elds related to energy-related functional and sustainable materials including fuel cells, photovoltaics, nano-functional systems, etc.

Session Organizer: Tatsuya Nabeshima

Session 4 / 5 Universe Evolution and Matter Origin / Research Frontier of Developing Energy and Environmental-friendly Materials Chair: Fumihiko Ukegawa, University of Tsukuba Director, Center for Integrated Research Kazuyuki Kanaya in Fundamental Science and Engineering, 9:00-9:10 University of Tsukuba Opening Address and Introduction to CiRfSE Guillaume Unal CERN, Switzerland 9:10-9:45 Tentative: LHC/ATLAS and Higgs Chair: Eiji Nishibori, University of Tsukuba Center for Materials Crystallography (CMC), Bo Iversen 9:45-10:20 Aarhus University Watching nanocrystals form 10:20-10:45 Break Chair: ShinIchi Esumi, University of Tsukuba Roy Lacey State University of New York at Stony Brook 10:45-11:20 Particle correlation studies in RHIC-BES: Probes for the critical end point in the QCD phase diagram Chair: Junji Nakamura, University of Tsukuba National Synchrotron Radiation Laboratory, Junfa Zhu University of Science and Technology of China 11:20-11:55 Applications of synchrotron radiation soft X-ray spectroscopies in the studies of energy-related functional materials 11:55-13:00 Lunch (3F Convention Hall 300) Session 5: Research Frontier of Developing Energy and Environmental-friendly Materials (4F Conference Hall 405) Chair: Yutaka Moritomo, University of Tsukuba Cheng-Hao Chuang Department of Physics, Tamkang University 13:00-13:35 X-ray spectroscopic study for different surface bonding environments of graphene oxide

41 Photon Factory, Institute of Materials Structure Shin-ichi Adachi 13:35-14:05 Science (IMSS), KEK Visualizing bond formation in solution with femtosecond X-ray scattering 14:05-14:15 Break The Institute for Solid State Physics (ISSP), Yoshihisa Harada Synchrotron Radiation Research Organization, 14:15-14:45 the University of Tokyo A new perspective on the structure of water: An electronic structure study Division of Physics, Faculty of Pure and Hideharu Niwa Applied Sciences, University of Tsukuba 14:45-15:10 Operando soft X-ray emission spectroscopy of non-Pt oxygen reduction catalysts for polymer electrolyte fuel cells 15:10-15:20 Break Chair: Junfa Zhu (National Synchrotron Radiation Laboratory, University of Science and Technology of China) Department of Chemistry and Department of Yu Kwon Kim 15:20-15:55 Energy Systems Research, Ajou University

Enhanced catalytic activity of chemically modifi ed TiO2 nanocrystals Division of Applied Chemistry, Faculty of Shin-ichiro Fujita Engineering , Hokkaido University 15:55-16:25 Mechanism of methanol synthesis over Cu/ZnO: Difference between CO2 and CO hydrogenations 16:25-16:35 Break Chair: Tatsuya Nabeshima, University of Tsukuba Global Research Center for Environment and Energy Tsuyoshi Takata 16:35-17:05 based on Nanomaterials Science (GREEN), NIMS Development of photocatalysts for water splitting under visible light irradiation Tsukuba Research Center for Interdisciplinary Junpei Kuwabara Materials Science (TIMS), Graduate School of 17:05-17:30 Pure and Applied Sciences, University of Tsukuba Practical synthetic method of conjugated polymer materials for organic photovoltaics

42 5-2

Applications of synchrotron radiation soft X-ray spectroscopies in the studies of energy-related functional materials

Junfa Zhu

National Synchrotron Radiation Laboratory, University of Science and Technology of China

Fundamental understanding of the electronic properties of energy-related functional materials as well as their structural evolution after they served in real devices is essential to the development of more effi cient devices for clean energy. Recently, Lithium/sulfur (Li/S) rechargeable batteries have attracted much attention due to their high theoretical specifi c capacity and energy compared to those of current lithium-ion cells. However, the application of Li/S batteries is still hampered by short cycle life. Sulfur–graphene oxide (S- GO) nanocomposites have shown promise as cathode materials for long-life Li/S batteries. However, the capacity decay still needs to be improved for commercially viable batteries. In this presentation, I will introduce our recent ex-situ studies on the electronic structure of S-GO and its evolution when served as cathodes in real batteries with various numbers of discharge– charge cycles using soft synchrotron radiation X-ray spectroscopies including near edge X-ray absorption fi ne structure (NEXAFS), X-ray emission spectroscopy (XES) and X-ray photoemission spectroscopy (XPS). It is found that in the S-GO nanocoposites, the moderate chemical interaction between sulfur and GO can preserve the intrinsic electronic structure of GO and also immobilize the sulfur and polysulfi des on the GO sheets. When they served as cathode materials in Li/S batteries, the chemical structures of the S-GO nanocomposites change considerably with increasing number of discharge-charge cycles. These changes are attributed to several unexpected chemical reactions of lithium with S-GO nanocomposites occurring during the discharge-charge processes. In addition, the morphology of the S-GO nanocomposite cathodes also change signifi cantly with increasing the number of cycles. These surface morphological/chemical structural changes of the S-GO nanocomposite cathode are signifi cant factors that infl uence the battery performance. The information we gain here through these studies may provide a general insight into fundamental understanding of the degradation mechanisms of the Li/S batteries and will be helpful for the optimal design of novel cathode materials.

43 5-3

X-ray spectroscopic study for different surface bonding environments of graphene oxide

Cheng-Hao Chuang1, Yu-Xun Chen1, Yun-Chieh Yeh2, Chun-Wei Chen2, Sekhar C. Ray3, Chia-Hao Chen4, Pagona Papakonstantinou5, Way-Faung Pong1, and Jinghua Cuo6

1Department of Physics, Tamkang University, Tamsui 251, New Taipei City, Taiwan 2Department of Material Science and Engineering, National Taiwan University, Taipei 106, Taiwan 3School of Physics, DST/NRF Centre of Excellence in Strong Materials and Materials Physics Research Institute (MPRI); University of the Witwatersrand, P/Bag 3, WITS 2050, Johannesburg, South Africa 4National Synchrotron Radiation Research Center, 300 Hsinchu, Taiwan 5Nanotechnology and Advanced Materials Research Institute, University of Ulster, Newtownabbey, UK 6Advanced Light Source, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA

Graphene oxide (GO) colloids dispersed well in the aqueous solution are relied on the hydrophic property and negatively-charged surface by the carboxylic acid and hydroxyl groups, since the individual graphene sheets are exfoliated and repulsed by the surface stabilizers during the chemical oxidation process. The introduction of surface functional group leads into the disruption of the crystalline structure and reorganization of perpendicular π* orbital in GO materials, showing the electronically property insulated and bandgap opened. To restore in a certain extent, the reduction of GO (r-GO) is recognized for different methods such as the strong deoxidizer, hydrothermal, vacuum annealing, and electrochemical reduction. GO, r-GO, and doped GO have widely been used in catalysis, biologic device, supercapacitor, Li- related materials, and solar cell system. In terms of the external effect (Oxygen/Nitrogen) and internal effect (structural defect/hexagonal network), the structural property and binding environment of GO-related materials are interpreted by the combination of X-ray absorption and emission spectroscopic study. Owing to the energy and momentum conservation between X-ray photon and crystalline phonon, the partial density of states (pDOS) with the element selection can draw the change of electronic and chemical structure of composite GO systems. Here, the integration of graphene synthesis and pattern-writing by scanning electrochemical microscopy (SECM) technology is able to develop the hydrophic interface of GO with the electron conductivity and nontoxic function for the biosensor and bioelectronics application, since the negatively-potential reduction and proton ion reaction occurred at the region of working electrode make GO colloids converted to rGO fl akes. Variations in the chemical and bonding environments of graphitic and non-graphitic domains are characterized by X-ray spectroscopic measurements, for further graphene-related advancement and expansibility in the wet environment.

44 5-4

Visualizing bond formation in solution with femtosecond X-ray scattering

Shin-ichi Adachi

Photon Factory, Institute of Materials Structure Science (IMSS), KEK

Bond formation is an essential process in chemistry, but it is challenging to keep track of detailed atomic movements associated with bond formation because of its bimolecular nature. Bond formation in solution phase has been especially elusive because it is diffi cult to initiate and follow such diffusion-limited bimolecular processes with ultrafast time resolution. In this – regard, Au oligomer complex, [Au(CN)2 ]n, offers a good model system in which to study the dynamics of bond formation in solution (Rawashdeh-Omary M A et al., J. Am. Chem. Soc. 123: 11237–11247, 2001; Iwamura M et al., J. Am. Chem. Soc. 135: 538–541, 2013). Using femtosecond time-resolved X-ray scattering, we successfully visualized in real time the birth of – a gold trimer complex, [Au(CN)2 ]3, that occurs via photoinduced formation of Au-Au covalent bonds (Kim K H et al., Nature 518: 385-389, 2015). The ground state of the trimer has Au atoms that are weakly bound to each other by aurophilic interaction and aligned in a bent geometry. Upon photoexcitation, the ground state rapidly converts into the fi rst excited state where Au-Au covalent bonds are formed among Au atoms aligned in a linear geometry. Subsequently, the state transforms to a triplet state in 1.6 ps while accompanying further contraction of Au-Au bonds by 0.1 Å. Later, the triplet state of the trimer converts to a tetramer on nanosecond time scale. This work showcases the possibility of tracking detailed structural changes in solution with sub-ps temporal and sub-angstrom spatial resolutions, thanks to the advent of X-ray free electron lasers and the advance of data analysis of time-resolved solution scattering data.

45 5-5

A new perspective on the structure of water: An electronic structure study

Yoshihisa Harada1,2

1Institute for Solid State Physics, The University of Tokyo 2Synchrotron Radiation Research Organization, The University of Tokyo

X-ray and neutron diffraction techniques have long been used as a direct probe of the hydrogen bond network of liquid water, while in this decade X-ray spectroscopic techniques have been widely used with the development of high brilliance synchrotron radiation source. X-ray absorption (XAS) and emission (XES) spectra of liquid water are one of the recently debated approaches to determine the local hydrogen bond network of liquid water through observation of its local valence electronic structure (Nilsson A and Pettersson L, Chem Phys 389: 1-34, 2011). Here we review our X-ray emission technique and spectroscopic results including temperature (Tokushima T et al., Chem Phys Lett 460: 387-400, 2008), isotope (Tokushima T et al., J Electron Spectrosc Relat Phenom 177: 192-205, 2010) and polarization (Tokushima T et al., J Chem Phys 136: 044517 1-7, 2012) dependence by referring to those debates. In addition, recent high resolution O 1s resonant inelastic X-ray scattering (RIXS) spectra add information about vibrational energy in the OH-stretching mode. Figure 1 shows a comparison of the energy separation in the RIXS spectrum at XAS pre-edge excitation of liquid

H2O water with the OH stretching mode by Raman spectroscopy (Harada Y et al., Phys Rev Lett 111: 193001 1-5, 2013). The RIXS spectrum is blue shifted because water molecules with a highly weakened or broken donating hydrogen bond are selected by the pre-edge excitation. We will also show evidence of this selectivity by excitation energy dependence of the RIXS vibrational structure, which strongly supports the interpretation of our O 1s XAS/XES results in terms of a mixture (micro-heterogeneity) model, where the network is considered as a mixture of various hydrogen bond confi gurations. The ‘vibrational RIXS’ technique bridges hydrogen bond confi guration and the electronic structure of water, which can be applied to a wide range of solutions in the near future.

46 5-6

Operando soft X-ray emission spectroscopy of non-Pt oxygen reduction catalysts for polymer electrolyte fuel cells

Hideharu Niwa

Division of Physics, Faculty of Pure and Applied Sciences, University of Tsukuba

Polymer electrolyte fuel cells (PEFCs) have attracted much attention in terms of applications in fuel cell vehicles and combined heat and power systems due to their high energy conversion effi ciency. Carbon-based oxygen reduction catalysts show high oxygen reduction reaction (ORR) activities and are expected to be cathode catalyst alternative to conventional Pt catalysts for PEFCs. The origin of their ORR activity should be clarifi ed to enhance the activity. We have developed a vacuum compatible cell for in situ/operando soft X-ray emission spectroscopy (XES) to observe the element-specifi c electronic structure and to elucidate the role of iron species in the ORR (H. Niwa et al., Electrochem. Commun. 35: 57-60, 2013). Iron phthalocyanine (FePc) ink was used for in situ experiment under atmospheric gas conditions and carbon-based cathode catalysts prepared by pyrolyzing a mixture of FePc and phenolic resin were used for operando experiment under PEFCs working condition. In situ/operando XES measurements were performed at BL07LSU in SPring-8 using ultrahigh resolution soft X-ray emission spectrometer (Y. Harada et al., Rev. Sci. Instrum. 83: 013116, 2012). In situ Fe

2p XES spectra of FePc under atmospheric O2 and Ar gas conditions showed clearly different energy loss features. This spectral change directly indicates oxygen adsorption to iron and a charge transfer between Fe 3d of FePc and the π* state of adsorbed O2. From operando Fe 2p XES spectra of FePc-based catalysts obtained at 1.0 V, it is found that an oxidized iron sites such as Fe-Nx sites exist and are active for oxygen adsorption, which is not expected from ex situ results in which metallic iron sites dominate. Detailed results and their ORR mechanism will be discussed.

47 5-7

Enhanced catalytic activity of chemically modifi ed TiO2 nanocrystals

Yu Kwon Kim

Department of Chemistry and Department of Energy Systems Research, Ajou University

TiO2 nanocrystals of a well-defi ned shape with a regular size distribution can be synthesized using a surfactant under controlled reaction conditions. The synthesized TiO2 nanocrystals are mostly in anatase phase with a bandgap of about 3.0 – 3.2 eV and show a good photocatalytic activity under UV illumination. This photocatalytic activity can be tuned by post-treatments such as annealing under NH3/O2/H2 and chemical treatments in HF/NaOH which may introduce or eliminate surface/bulk defects associated with gap states and may change the size and shape of the nanocrystals as well as their crystallinity. Here, we present our experimental results on the post-treatment-dependent photoactivity of our shape-controlled TiO2 nanocrystals. Our results show that the photoactivity of the TiO2 nanocrystals can be enhanced further when the type and the density of defects in the bulk as well as on the surface are regulated in a way to enhance the surface defect density. The type and density of defects in the bulk are redistributed during thermal treatments via diffusion and the photoactivity is found to be enhanced as the non-uniform defect distribution between surface and bulk induces surface defects which can induce paramagnetic O- species on the surface under ambient condition. Also, the chemical treatments in HF/NaOH result in successive etching of surface layers which can eliminate or induce new type of defects on the surface. We fi nd that the photoactivity of the chemically treated TiO2 nanocrystals changes depending on the type of defects induced on the surface.

48 5-8

Mechanism of methanol synthesis over Cu/ZnO: Difference between CO2 and CO hydrogenations

Shin-ichiro Fujita

Division of Applied Chemistry, Faculty of Engineering, Hokkaido University

It was well known that methanol synthesis from CO2 proceeds much more rapidly than that from CO over Cu/ZnO based catalysts. But, its reason was controversial for a long time. In the present study, methanol synthesis from CO2 and from CO was carried out at atmospheric pressure over a Cu/ZnO catalyst and the surface species formed were analyzed by diffuse refl ectance FT-IR spectroscopy and temperature programmed desorption. It was revealed that

CH3OH and CO were produced from CO2-H2 through parallel pathways. Two types of formate species, HCOO-Cu and HCOO-Cu and HCOO-Zn, and zinc methoxide were formed in the course of methanol synthesis from CO2. HCOO-Cu and HCOO-Zn were hydrogenated to methoxide. It was also found that CH3O-Zn is rapidly hydrolyzed to methanol. A comparison of the rates of hydrogenation of the formates with that of methanol synthesis from CO2 suggested that methanol synthesis from CO2 occurred via the hydrogenation of HCOO-Cu.

The methanol synthesis from CO proceeded at a rate much slower than that from CO2, HCOO-

Zn and zinc methoxide were formed in the course of the CO-H2 reaction. No HCOO-Cu was detected. The amount of the zinc methoxide formed in the CO-H2 reaction greatly exceeded that formed in the CO2-H2 reaction. The rate of the formation of methoxide in the CO-H2 reaction was in reasonable agreement with that of the hydrogenation of HCOO-Zn. On the basis of these fi ndings, the difference in rate between methanol synthesis from CO2 and from CO was ascribed to the difference of the formate species involved in the reactions and the presence and absence of H2O in the reaction systems.

49 5-9

Development of photocatalysts for water splitting under visible light irradiation

Tsuyoshi Takata1*, Chengsi Pan1, and Kazunari Domen1,2

1Global Research Center for Environment and Energy based on Nanomaterials Science(GREEN), National Institute for Materials Science(NIMS), 1-1 Namiki, Tsukuba-city, Ibaraki, 305-0044, Japan 2Department of Chemical System Engineering, School of Engineering, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, 113-8656, Japan

Utilization of solar energy is an important subject to solve energy and environmental problems. Photovoltaic devices generate electricity from sunlight and are an increasingly common sight in recent years. We have another challenge, artifi cial photosynthesis, mimicking nature’s way of producing fuel from sunlight. Solar energy can be directly converted to fuel by artifi cial photosynthesis, which is more advantageous in view of energy storage and scalability. Direct water splitting to H2 and O2 on a semiconductor photocatalyst is one of the simplest models of artifi cial photosynthesis. To effi ciently perform this reaction under sunlight is an attractive way for producing clean and renewable hydrogen fuel. In view of thermodynamics, the bandgap of the used semiconductor must be larger than the dissociation energy of water, 1.23 eV, and is preferably much larger due to the existence of overpotentials. So the challenge of splitting water with smaller light energy to effi ciently harvest solar energy has been a core subject of this research area. Various wide gap (> 3 eV) photocatalysts for water splitting had been developed in the last century, but they can utilize only UV-light. Later, visible-light-sensitive semiconductor photocatalysts have been variously explored for utilizing broader sunlight spectrum. Despite huge effort to develop such photocatalysts, only a limited number of successful results has been reported to date. Especially, we have intensively studied metal oxynitrides as photocatalysts for visible-light-driven water cleavage. Among them, very recently, we newly designed a complex-perovskite-type transition metal oxynitride as a photocatalyst operable under wide range of visible light. The recent advances in our study on water-splitting photocatalysts will be introduced.

50 5-10

Practical synthetic method of conjugated polymer materials for organic photovoltaics

Junpei Kuwabara and Takaki Kanbara

Tsukuba Research Center for Interdisciplinary Materials Science (TIMS), Graduate School of Pure and Applied Sciences, University of Tsukuba

Conjugated polymers have been extensively investigated as materials for organic electronic devices such as organic photovoltaics (OPVs), organic light emitting diodes, and organic fi eld-effect transistors. In particular, OPVs are expected as a next-generation photovoltaic possessing several advantages in terms of fl exibility and light weight. For wide applications of the OPV technology, a practical production method of conjugated polymer materials is highly required because conventional methods do not satisfy requirements in production costs and environmental issues. The conventional methods require metal-containing compounds as starting materials. The use of the metal-containing compounds causes cost and environmental issues because of their multi-step synthesis and toxicity. For overcoming these issues, we investigated a new synthetic method of conjugated polymers, which does not required the metal-containing compounds. In concrete terms, a polycondensation reaction via direct C-H functionalization has been developed as an improved synthetic method (Kuwabara J & Kanbara T, J. Synth. Org. Chem., Jpn. 72: 1271–1277, 2014). This method is applicable in syntheses of various conjugated polymers. In addition, the optimization of the reaction conditions allows to afford conjugated polymers with high molecular weight and high purity which are regarded as important factors affecting performance in OPVs. In fact, the obtained polymer showed better performance in OPV than same polymer prepared by a conventional method (Kuwabara J et al., Adv. Funct. Mater. 24: 3226–3233, 2014). The dominant factor for the improved performance was high purity of the polymer. The details of the synthetic method and the OPV application will be presented.

Conventional sythetic method for conjugated polymers

Cat. n+nM Ar1 M Br Ar2 Br Ar1 Ar2 + 2n MX n M = metals

This method

Cat. n+nH Ar1 H Br Ar2 Br Ar1 Ar2 + 2n HX n

51 NOTE

52 6

Tuseday, September 29 Frontier Study in Policy and Planning Sciences Computing Enterprise Information Systems Venue: Conference Room 401 Frontier Study in Policy and Planning Sciences and in Computing and Enterprise Information Systems

The session is organized to promote academic exchange between University of Tsukuba and the Hong Kong Polytechnic University based on the inter-university agreement. The possibility of applying state of the art (information) technology to solve our social problems will be discussed.

Session Organizers: Shun Watanabe and Yukie Sano Part One Chair: Shun Watanabe, University of Tsukuba Vincent Ng The Hong Kong Polytechnic University 9:00-9:30 Learning Analytics on Student Learning Engagement with Peer Assessment Hiroichi Kawashima University of Tsukuba 9:30-10:00 Lessons Learned from the Introduction of the Prefecture-wide Medical Record Sharing System in the Saga Prefecture, Japan Korris Chung The Hong Kong Polytechnic University 10:00-10:30 Urban Planning and Unmanned Aerial Vehicles Hisashi Kurata University of Tsukuba 10:30-11:00 The Value of Information in Supply Chain Management: Review of Information Sharing Research and its Directions Man Ho Allen Au The Hong Kong Polytechnic University 11:00-11:30 Cybersecurity and Privacy Yukie Sano University of Tsukuba 11:30-12:00 How People Reacted to the 3.11 Earthquake in Japanese Online Social Media Part Two Chair: Allen Au, The Hong Kong Polytechnic University Michimasa Kanno University of Tsukuba 13:15-13:30 Change of Chinese Character Usage in Japan: The Case of Akutagawa Prize- winning Works Chi Kit Ng and Tsz Hei Yeung The Hong Kong Polytechnic University 13:30-14:00 sPADAP: An Anti-Drug Abuse Mobile Platform for Family Support Keisuke Akiho University of Tsukuba Economic Review and Evaluation from Offi cial Development Assistance 14:00-14:15 Infrastructure Project Impact, Case Study on Sihanoukville Port Development in Cambodia Han Mingshan University of Tsukuba 14:15-14:30 Comparing the Effectivenesses of Evaluation Functions for Quoridor Angus K. Y. Lam The Hong Kong Polytechnic University 14:30-14:45 How Can Computer Help in Mathematics Education? Naoki Hashimoto University of Tsukuba 14:45-15:00 On the Probability Density of the Time Intervals between Consecutive Transactions in the Financial Markets

53 Part Three Chair: Yukie Sano, University of Tsukuba Yuka Takabatake University of Tsukuba 15:15-15:30 The Infl uence of Public Participation to Spatial Change in the Besançon Tram Project Ka Fai Chan The Hong Kong Polytechnic University 15:30-15:45 E-Voting Hidetaka Mori University of Tsukuba 15:45-16:00 Factor analysis of a move to a “Karino-machi” Oscar Lok and Patrina Lu The Hong Kong Polytechnic University 16:00-16:30 On the Design, Analysis and Application of Multiple Flying Drones Yasuaki Kikukawa University of Tsukuba 16:30-16:45 Estimating Business Relationships between Business Establishments Akihiro Tanaka University of Tsukuba 16:45-17:00 Improved LP-based Algorithms for Testing Copositivity

54 6-1

Learning analytics on student learning engagement with peer assessment

Vincent Ng, KH Liu and Lung Chi Hong

Department of Computing, The Hong Kong Polytechnic University

Many students are often labeled as passive learners when they attend lectures quietly and have no classroom interaction. For these students, it is diffi cult for teachers to tailor individual learning paths to provide the just-in-time material. Student engagement in learning is a common challenge nowadays. One popular approach is to promote active learning via pre-class activities. Recently, we have attempted to analyze student learning behavior through peer assessment and fl ipped classroom arrangement. Our aim is to assemble different sources of student data, such as access records of the learning management system, student feedbacks, and their academic performance, for a better understanding of their learning behavior and outcomes. A compulsory subject, Database Systems and Applications, is selected. Two special classes of the subject have adopted the fl ipped classroom arrangement. Video clips, pre-class exercises, notes and short tests of these classes have been placed in the Open EdX platform as mini-learning units. For the 81 students registered, every single click on the system was recorded. After the classes, an in-class quiz was conducted on the material. The quiz was graded by their peers as well as the lecturers afterwards. For the collected data, there are over 26,000 raw access records of the Open EdX platform which include video access log. From the raw data, it is found that the average student activity is quite high and the average click count is close to 200 per student with around 70% of them have over 100 click count. It is also observed that some students attempted to change the speed of the video and others have changed the sequence of learning units. We then defi ned different learning engagement steps based on click-trails. Integrated with these engagement steps, student academic results, and peer assessments, data analysis have been conducted and are presented in the paper.

55 6-2

Lessons learned from the introduction of the prefecture-wide medical record sharing system in the Saga Prefecture, Japan

Hiroichi Kawashima

Professor, Institute of Policy and Planning Sciences, University of Tsukuba, Japan

Containing spiraling healthcare costs is a common agenda in ageing societies. Health expenditure as a percentage of GDP has been increasing in OECD countries. The percentage of GDP in Japan has risen from 7.4% in 2000 to 10.2% in 2013 and it is predicted that the percentage will reach 11.7% in 2060. Among various measures for controlling health expenditures, a data-aided analytical approach is an approach that Japan has lagged behind advanced OECD countries such as Austria, Canada, UK, France and Germany. The introduction of the medical record sharing system among hospitals and clinics covering hierarchical medical districts is one of the data-aided analytical approaches that can rationalize the medical expenditures. There have been many efforts to cover a broader area with the medical record sharing system in Japan since 1990s. In 2010, the Government of Saga had succeeded in introducing the region-wide medical record sharing system in the Saga Prefecture for the fi rst time in Japan. Having conducted some interviews with key stakeholders in introducing and operationalizing this medical record sharing system in Saga, this research has identifi ed three lessons from the case of Saga. The fi rst one is the importance of a pro-sharing institutional setting that can build consensus for the introduction of a medical record sharing system among three key regional players: 1) regional private doctors’ association, 2) university hospital and 3) healthcare administration department in the prefectural government. The second one is the availability of fi nancial resources to cover the necessary costs for creating interfaces and making links among medical record systems of hospitals and clinics in the region. In reality, it is hard to build consensus on joint-coverage of necessary costs among various medical institutions at the same time. The third one is a realistic technology choice among different medical record sharing system designs. Ideally, having a centralized common database might be a rational choice. In reality, setting an intermediary system would be a feasible choice since it would involve various hospitals that have been operating different medical record systems so far. In conclusion, the case of the prefecture-wide medical record sharing system in Saga exemplifi es that there are three important factors to be considered when we think about data- aided analytical approaches in medical data integration: 1) a pro-sharing institutional setting, 2) available fi nancial resources to fi ll the resource gaps, and 3) a feasible technology choice that can involve as many stakeholders as possible.

56 6-3

Urban planning and unmanned aerial vehicles

Korris Chung

Department of Computing, The Hong Kong Polytechnic University

Unmanned aerial vehicles (UAVs), commonly known as drones, have recently been demonstrated with profound usage in our daily lives, e.g. jogging and athletics. It is very likely that they are going to emerge in our cities as cars do. About a century ago, cities didn’t know how to handle these “fast moving” machines in terms of who had the right to the road. Likewise, sooner or later, every city needs to “plan” the airspace, particularly, the zoning for drones. While drones are under rigorous development for diverse applications, this presentation will give a brief review of different drone designs, e.g., quadcopter, hexacopter, and micro, and covers some interesting and representative applications. Emphasis will be on the path planning for drones arising from different applications, with the purpose of highlighting the involved “airspace” so that urban planners may get a thorough understanding of the requirements. In addition, some interesting ideas of drone usage, e.g. advertisement in indoor shopping mall and outdoor open space will also be shared. The cooperative and coordination issues of multiple drones will be discussed.

57 6-4

The value of information in supply chain management: Review of information sharing research and its directions

Hisashi Kurata

Faculty of Engineering, Information & Systems, University of Tsukuba

Now is the information age. Many people are talking about information technology (IT) buzzwords such as ERP, mobile, ubiquitous, cloud, big data, IoT, omnichannel, and so on. Businesses have invested much money in IT, and researchers have published articles that discuss the successes and failures of IT implementation in real businesses. So far, the majority of discussions about management information systems (MIS), the interdisciplinary study of IT and businesses, have considered real situations in which companies succeeded or failed in applying IT systems to their businesses. Additionally, empirical studies have revealed factors that enable a fi rm to use state-of-the-art systems to gain a competitive edge. An important but less discussed issue of current MIS is why businesses need IT, or more fundamentally, information. This review focuses on the benefi ts that fi rms using IT systems might obtain and why fi rms need such systems. In particular, as this research into supply chain management considers effective and effi cient alliances between fi rms and a smooth way to provide value to end-customers, we focus on the following key words: bullwhip effect (the distortion of information that passes through a supply chain), supply chain coordination (the mechanism that gives supply chain members an incentive for global optimization), and customer-driven demand (demand endogenously infl uenced by customers’ decision processes and environments). First, we review the role of information sharing between supply chain members, including an explanation of how technology enabling the exchange of information between chain members can improve the performance of either each supply chain member or the entire chain as well as how technology can provide high value to end customers. Second, as one of the most pressing issues in modern operations management, we discuss the role of customers as essential but often-ignored participants of a supply chain system and how technology can connect customers with fi rms. Finally, following a discussion of the aforementioned three key words, we present several promising themes in supply chain management that could serve as bases for future research. In addition, several comments from supply chain experts are presented to support our discussion.

58 6-5

Cybersecurity and privacy

Man Ho Allen Au

Department of Computing, The Hong Kong Polytechnic University [email protected]

It is often mentioned that we have to trade privacy for security. This has lead to the debate on the topic of how much privacy shall we give up for security. In this talk, we survey some recent results which demonstrated that, under some specifi c settings, both factors could be achieved simultaneously. We review some existing efforts in accurately defi ning the noti on of privacy. In particular, a privacy breach can be divided into two categories, namely, the leakage of information from the computation process and the leakage from the computation outcome. After that, we discuss the security and privacy requirements of some existing applications. We fi rst review authentication and discuss some techniques in which user privacy can be preserved. Next, we discuss cloud storage and illustrate the importance of encryption if data privacy is to be maintained. Then, we survey some recent results to show how encrypted data can be checked, shared, searched and used without compromising data privacy. The fi nal example is on data analytic in which we reviewed some of the latest results on privacy-preserving machine learning. Finally, we conclude the talk with some challenging issues when privacy is put into considerations. These include accounting, auditing and revocation.

59 6-6

How people reacted to the 3.11 Earthquake in Japanese online social media

Yukie Sano1, Misako Takayasu2, Kazuya Sato2, KentaYamada3,4, Wataru Miura 2 and Hideki Takayasu2,5,6

1Faculty of Engineering, Information and Systems, University of Tsukuba 2Interdisciplinary Graduate School of Science and Engineering, Tokyo Institute of Technology 3Graduate School of Engineering, The University of Tokyo 4PRESTO, Japan Science and Technology Agency 5Sony Computer Science Laboratories, Inc. 6Meiji Institute for Advanced Study of Mathematical Sciences

Online social media have ubiquitous in this century and people use them in both everyday life and emergencies. Here we show two empirical results of how people reacted in the online social media at the Great East Japan Earthquake (the 3.11 Earthquake) in 2011 by investigating Japanese Twiter and blog spaces. Firstly, we investigated whole Japanese tweets (approximately 180 million tweets from 3.7 million accounts) that sent one week after the 3.11 Earthquake. Twitter Japan Inc. offi cially provided the data via project 311 (https://sites.google.com/site/ prj311/) for all researchers who want to contribute to prevent future disasters by analyzing the data for a limited time. From the data, we focused on one rumor that appeared in the immediate aftermath of the quake and later turned out to be misinformation. Since none can record precisely and accurately rumor spreading and convergence process in previous centuries, online social media can record when, who, and how a rumor spread and converge in details. From the data, we confi rmed that fi nally 88,657 accounts involved in both the rumor spreading and the correcting processes. We found that one correction tweet which was originated from a city hall account diffused enormously and contributed to the rumor convergence. We also demonstrated a stochastic agent-based model, which is inspired by the SIR (Susceptible-Infected-Recovered) model, can reproduce the observed rumor dynamics. Secondly, we investigated Japanese blog posts (approximately 3.2 billion posts) for six years since 2007. We discuss the emotional changes before and after the 3.11 Earthquake by focusing on appearances of whole Japanese adjectives. We found that special emotion adjectives, such as ‘frustrating’ which involve the want to help others but the person has no means to and feel frustrated, considerably increased. We conclude that online social media is a novel tool for observing real social phenomena and open the new age of computational social sciences.

60 6-7

Change of Chinese character usage in Japan: The case of Akutagawa Prize-winning works

Michimasa Kanno

College of Policy and Planning Sciences, University of Tsukuba

Many kinds of characters, such as Hiragana, Katakana, Kanji, Roman alphabet, and so on, are usually used when we write something in the Japanese language, and people sometimes get confused on how to use them appropriately. The most common problem is what charac- ter, especially either Hiragana or Kanji, should I use for writing a word because a word can be written in many ways, unlike in other languages such as English, German, French, etc. There were two purposes of this study. The fi rst was to calculate and reveal recent use rates of Chinese characters, which has been one of the most common indicators for sentences in Japan. According to preceding studies, it was predicted that Chinese characters would perish by the end of the 22nd century because use rates of Chinese characters had decreased from the beginning of the 20th century. By revealing the recent rates, it could be verifi ed whether the prediction was correct or not. The other purpose was to assess the rates of fl uctuation statisti- cally. This was done because fl uctuation had been evaluated not statistically but subjectively. Besides, by introducing a statistical method to the data from preceding studies, the relevance of past research could be confi rmed. In prior research, an investigation into Akutagawa prize- winning works published from 1935 to 1985 was conducted; this prize is the oldest and most popular one for serious literature in Japan. Following that study, I added an investigation into the works published from 1986 to 2015. Each rate represents the corresponding work and each sample contains other works from the same period of 5 years. For example, rates of works published from 1986 to 1990 are called “sample 1.” Subsequent others follow the same logic until “sample 6” which contains rates from 2011 to 2015. On the samples, I conducted a Kruskal-Wallis test, which is one of the statistical hypothesis tests and a non-parametric method for examining whether samples are generated from the same distribution or not. As a result, there were no signifi cant differences among 5-year-containd samples from 1986 to 2015 (H = 2.5227, p = .785, n.s.). This implied that rates from 1986 to 2015 have not been fl uctuating but remained stable. Because this conclusion is not positively supported in terms of statistics, a supplemental test is needed in order to reinforce the relevance of the conclusion. On the other hand, I introduced the same analysis to the preceding study, whose object was the same works published from 1935 to 1985. In that case, the null hypothesis was rejected (H = 27.8224, p = .0002), which meant that rates from 1935 to 1985 seemed to be fl uctuating statistically and proved that the subjective assessment of rates decreasing at the beginning of 20th century was statistically true.

61 6-8

sPADAP: An anti-drug abuse mobile platform for family support

Chi Kit NG and Tsz Hei Yeung

Department of Computing, The Hong Kong Polytechnic University

Drug abuse amongst young people has been a recurring problem in Hong Kong. In a recent report, it has been found that there are “hidden youths” who might have drug abuse issues and their parents have not noticed until a few years later. Hence, there is a need to aid parents in the early detection of any potential drug abuse of their kids and the associated knowledge of how to handle the situation when it occurs. If parents can provide guidance and clear information about not using drugs to their children, it would greatly reduce the chance for them having drug abuse problem afterwards. Our project aims to develop a community of practice platform for parents to access timely anti-drug information, to have an intelligent alerting tool for detecting potential family drug abusers and to form a mutual support community between parents and other stakeholders such as social workers, anti-drug experts and teachers. The platform includes three mobile applications to support the different stakeholders. The intelligent alerting tool utilizing artifi cial intelligence based on an anti-drug abuse knowledge base with a mobile frontend has been developing to assist parents for possible early detection if there is a drug abuse case in family. If unfortunately, a drug abuse issue happens in a family, parents need timely assistance and peer support. A community support repository together with an advance search tool can aid these parents. Another component of the platform is to have the correct and easy to understand information of how to manage drug abuse issues. Other than the usual mobile informative frontends, we are trying augmented reality and cyber- physical technologies for easier acceptance by young people.

62 6-9

Economic review and evaluation of Offi cial Development Assistance infrastructure project impact: Case study on Sihanoukville port development in Cambodia

Keisuke Akiho1 and Naohisa Okamoto2

1Urban Planning Section, College of Policy and Planning Sciences, University of Tsukuba 2Professor, College of Policy and Planning Sciences, University of Tsukuba

The Japanese Offi cial Development Assistance (ODA) Loan has contributed to many economic and social infrastructure projects in developing countries. After the completion of the project, Japan International Cooperation Agency (JICA), the implementing agency of Japanese ODA, reviews and evaluates the project based on its relevance, effi ciency, effectiveness, impact, and sustainability. However, the evaluation takes place 2 years after the completion of the project. Infrastructure such as ports, roads, and railways sometimes take a long time until the occurrence of the impact. In order to improve the public’s understanding of international cooperation, it is important to review and evaluate the project after an extended period of time. Sihanoukville port, the only international port in Cambodia facing the ocean, has been developed by Japanese ODA Loan from 1990s. Since the port was heavily damaged during the civil war, JICA and Japanese government have been trying to support the rebuilding of said infrastructure. This study reviews and evaluates how Sihanoukville has been developed in chronological order, adjusting effects and infl uences of port development to the area, focusing on economic development in the hinterland area.

63 6-10

Comparing the effectiveness of evaluation functions for Quoridor

Han Mingshan

Management Science and Engineering, Faculty of Policy and Planning Sciences, University of Tsukuba

Quoridor is a famous board game which was designed by Mirko Marchesi and published by Gigamic Games. The game is played on a board of 9 rows and 9 columns by 2 or 4 players. Each player has a pawn which is put at each edge of the board at the beginning. The objective of the game is to move the player’s own pawn to the opposite side of the board as quickly as possible. The most interesting part of this game is that each player is given a certain number of fences to hinder the other players’ way to the goal. By placing the fences, the game has many possible moves and makes a variety of positions. Players can either move their own pawn a step or place a fence during their turn. In computer science, construction of algorithms to play board games is one of the exciting fi elds. For such algorithms, we need evaluation functions, which estimate the goodness of a given position of a game. Few evaluation functions for Quoridor are known. The evaluation functions are essentially based on the distance from the player’s own pawn to the goal. In this research, we introduce some evaluation functions and compare these evaluation functions by applying several positions on the game progress.

64 6-11

How can computers help in mathematics education?

Angus K. Y. Lam

Department of Computing, The Hong Kong Polytechnic University [email protected]

With the advancement in technology, the concept of ubiquitous computing has become a reality. Computing devices have become an indispensable element of our daily life. For instance, it is common to see that everyone just focuses on their tablets or mobile phones on the train because of some addictive applications such as the famous game Puzzle & Dragons (PND). A look at the Apple App Store reveals that there are over a million of apps, arranged in more than fi fteen categories. The smart device has become a personal assistant for its owner in every aspect of his or her daily life. In this project, we study how a computing device can be used to facilitate the learning of mathematics in the form of games. Nowadays, there are many mini games to teach players the calculation of some equations. However, the equations are just of the very simple type such as elementary equations involving addition and multiplication. How to excite the player so that they will keep playing the game for an effective learning experience is the key that the creator has to consider. One has to pay attention to not just building an attractive interface, but also the content and the educational values. In this project, we put ourselves in the shoes of the players to understand what they really want and like. Through making the game more interesting and addictive, we hope that people can learn more about mathematics and be inspired to love the subject.

65 6-12

On probability density of time intervals between consecutive transactions in fi nancial markets

Naoki Hashimoto

Policy and Planning Science, University of Tsukuba

I am developing a simulator for fi nancial markets in Japan. Most fi nancial markets in Japan adopt the order-driven system. The buy offers and the sell offers are listed in the public order book. The highest buy (lowest sell) price is called the best bid (ask) price. When a new buy (sell) order arrives, and its buy (sell) price is equal or higher (equal or lower) than the best ask (bid) price, the order is executed at the best ask (bid) price. The new buy (sell) order is simply added in the public order book if the buy (sell) price of the arrived order is lower (higher) than the best ask (bid) price in the public order book. This continuous auction process is repeated until the close of the market. In my simulator, the order is assumed to arrive following a stochastic process. Thus, the essential part of my simulator is fi xed if the stochastic process and its parameters are fi xed. That is why I am interested in the stochastic process of the order arrivals in the Japanese fi nancial market. I start from the assumption that the time intervals of the orders follow an i.i.d. distribution. Various theoretical works assume that the stochastic process follows the Poisson process, that is, the density is the exponential distribution. For example, Li Meng et al. (2014) analyzed a behavior of the model based on the assumption of the Poisson process. It is reported, however, that the Poisson process is far from reality in the case of fi nancial markets. Miyazaki (2011) found that Pareto distribution gives a better fi t to this distribution. Zhu and Kishimoto (2015) found that compound distribution is to be considered. Although these seem to be the best results available now concerning the Japanese fi nancial market, their empirical analysis has a substantial shortage since the tick data they used are stamped on the second time scale. The second time scale is too coarse for analyzing time intervals of transactions in the fi nancial market in Japan. Recently, I newly obtained data whose time stamp is millisecond time scale, though noise is added to the original true time. Thus I can empirically check which models are more realistic. That is what I wish to present. The results suggest that the conclusion in Zhu and Kishimoto (2015) is substantially supported, but minor modifi cation is needed.

66 6-13

The infl uence of public participation on spatial change in the Besançon Tram Project

Yuka Takabatake1 and Kosuke Matsubara1,2

1Graduate School of Systems and Information Engineering, Master’s Program in Social Systems Engineering, University of Tsukuba 2Associate professor, University of Tsukuba

In general, it is said that France is a country with advanced public participation. After the Second World War, French government made efforts to introduce trams in an attempt to resolve many problems like moralization, environmental problems and hollowing out of central city. When the government reorganizes a city area by large-scale planning like the tram project, it puts emphasis on citizen participation. On the other hand, there are a lot of countries where the government would like to introduce a tram system in recent years, such as Asian countries and the developing countries especially in Africa. When thinking about the introduction of a tram system in these countries, we think that it is important to make a decision by consensus with inhabitants. Besançon, the capital of the Franche-Comté Region in France, is one of the historical cities where citizen participation is regarded as important. In addition to that, the tram project in Besançon is the latest case of introduction of a tram system in France. Therefore this paper focused on Besançon and the purpose of this paper is analyzing advantages and issues of citizen participation. To begin with, we summarized the outline of the tram project in Besançon. We think that it can be an important suggestion for city planning with inhabitants in various historical countries. At fi rst, in order to look in the characteristics of public participation in Besançon, we analyzed the reports which were written by Grand Besançon. And secondly, we considered the spatial changes through public participation. Finally, we analyzed the characteristics of spatial city change based on public participation and the possibility of application to other cities where the governments tries to introduce the tram system. It is important to improve cities so that citizens may learn the foundation of public participation and try to change the system of government through bottom- up approaches.

Keywords: Tramway, Public Participation, Spatial Change

67 Cryptography in GPUs

Chun Yin Leung

Department of Computing, The Hong Kong Polytechnic University

The Internet has become an indispensable part of our lives. Many of our daily activities, such as paying the bill by e-banking system, checking the school schedule on the e-system and chatting with our friends, relies on the Internet. We make use of various tools like WhatsApp, Line, WeChat, etc., for communication purpose. At the same time, it raised various security concerns. Encryption is the basic tool in securing the communication channel. The security requirements on the Internet has been increasing. Hypertext Transfer Protocol Secure (HTTPS), for instance, has already been widely used nowadays.

To cope with the increasing needs in the computational power for security-related services, researchers have been looking into different approaches. One direction to satisfy this increasing demands is to utilize modern Graphics Processing Units (GPUs) parallel computation ability.

GPUs are sophisticated parallel processing units due to the reasons that it is designed to process individual pixels on our a display. It is observed that this architecture is well-suited for a server to provide secure communication with its client. Specifically, the servers usually need to handle many encryption and decryption from different users simultaneously. If we implement the common encryption protocol with the GPU parallel computation ability, it should enhance the computation speed which would help improve the system’s efficiency. So, in this project, we are going to try to implement the commonly-used algorithm, for example, RSA, AES, DSA, etc. by GPU technologies such as CUDA or OPENGL.

68 6-15

Factor analysis of a move to a “Karino-machi”

Hidetaka Mori1 and Mamoru Taniguchi2

1Graduate School of Systems and Information Engineering, University of Tsukuba 2Faculty of Engineering, Information and Systems, University of Tsukuba

The Great East Japan Earthquake and tsunami that struck Japan on March 11, 2011, produced widespread and severe damage, especially in the Tohoku area of northern Japan. The Fukushima nuclear power plant accident has required the long-term evacuation of many residents. For them, a “Karino-machi” plan has been suggested as a plan by which a town existing before the earthquake is relocated to some other locale. Nevertheless, the opinions of affected residents have not been clarifi ed. This study clarifi ed the expectations and factors related to moving to a “Karino-machi,” specifi cally examining all target persons of the “Karino- machi,” who now live in Iwaki, Fukushima prefecture, which is located 300 km north of Tokyo. Results show that the distance from each town to the Fukushima Daiichi nuclear power plant affected differences of opinions related to the “Karino-machi.” Therefore, each town before the earthquake was expected to carry on the plan of “Karino-machi” in different ways according to that town’s circumstances. Results show that personal attributes produce different opinions related to their expectations for moving to a “Karino-machi.” Especially, attachment to areas where they had lived before the earthquake was a positive factor for moving to a “Karino- machi,” but attachment to the present living area was found to be a negative factor for moving to a “Karino-machi.”

69 6-16

On the Design, Analysis and Application of Multiple Flying Drones

Oscar Lok and Patrina Lu

Department of Computing, The Hong Kong Polytechnic University

In recent years, the AR. Drone products have created an impact on the entertainment market as well as the video games industry. The navigation and control technologies embedded in the micro Unmanned Aerial Vehicle (UAV) play an important role to the performance of the AR. Drone. In this presentation, a dynamic model for controlling multiple AR. Drones and the corresponding application are introduced. First, as uncertain dynamic obstacles are under considerations, how multiple UAVs work together in unexpected environments becomes one of the major concerns. The system is expected to be able to recognize obstacles, decide reliable navigation paths and make effi cient cal lings to UAVs according to the global data. Second, the effective algorithm of the system must be safe, stable and user friendly. Visual algorithms, inertial sensors calibration and attitude estimation are utilized to estimate the suitable velocity. Finally, for the application part, AR. Drones are designed as a navigator for travelling purpose. Drones are able to follow some predetermined paths for launching the navigation based on users’ destination selection. Some check points are considered as the milestones of the predetermined path during the navigation. When Drones arrive in the check point, the important traveling information of that check point will be introduced to the users’ electronic devices.

70 6-17

Estimating business relationships between business establishments

Yasuaki Kikukawa1, and Morito Tsutsumi2

1Graduate School of Systems and Information Engineering, University of Tsukuba 2Faculty of Engineering, Information and Systems, University of Tsukuba

In recent years, the use of business-to-business transaction micro data has advanced in Japan. This dataset contains information of business relationships between suppliers and customers, and has been applied to analysis of the supply chain, agglomeration of industry, and distance of the transaction. However, a drawback of the dataset is that it represents business relationships between headquarters. Therefore, we can fi nd the fi nancial fl ow but do not know the commodity fl ow. In order to know the commodity fl ow, we have to focus on business relationships between the business establishments, such as factories and warehouses. The objective of this study is to estimate business relationships between business establishments using the inter-fi rm transaction data and build a dataset of location information of business establishments. Then, we will discuss the applications of such a dataset to a variety of themes such as disasters and regional economies.

71 6-18

Improved LP-based algorithms for testing copositivity

Akihiro Tanaka, Akiko Yoshise

Graduate School of Systems and Information Engineering, University of Tsukuba Faculty of Engineering Information and Systems, University of Tsukuba

A symmetric matrix is called copositive if it generates a quadratic form taking no negative values over the positive orthant, and the linear optimization problem over the set of copositive matrices is called the copositive programming problem. Recently, many studies have been done on the copositive programming problem (cf, Dur, 2010). Among others, several branch- and-bound-type algorithms have been provided to test copositivity since it is known that the problem for deciding whether a given matrix is copositive is co-NP-complete (cf. Murty and Kabadi, 1987). In this talk, we propose some new branch-and-bound-type algorithms for this testing problem. Our algorithms are based on some subcones of the c opositive cone. We showed that one can detect whether a given matrix belongs to one of those cones by solving linear optimization problems. Numerical experiments suggest that those cones are a relatively large subset of a copositive cone and our algorithm is promising for determining upper bounds of the maximum clique problem.

72 7&8

September 28~30 Venues: Conference Room 405 (9/28) Network Resilience Joint Sessions: Natural Disasters Prevention and Management & Disasters Prevention and Conference Room 102 (9/29) Joint Sessions: Natural Disasters Prevention and Management & Disasters Prevention and Network Resilience

Our joint sessions will bring together professionals working in the fi elds of Earth Sciences, Environment, Civil Engineering & Urban Planning, as well as Disaster Emergency Response, with the aim of strengthening the scientifi c collaborations on Natural Disasters Prevention and Management between the University of Tsukuba and the world.

Session Organizers: Bogdan Enescu, Tomomi Kito, Yuji Yagi, Shun Watanabe, and Yoshiaki Osawa

Morning Session Chair: Bogdan Enescu, Gaku Shoji Yuji Yagi University of Tsukuba, Representative of “MegaQuake” Project 10:15-10:30 Welcome Address John Vidale Depart. Earth & Space Sciences, University of Washington 10:30-11:30 Anticipating the next great earthquake in the American Pacifi c Northwest 11:30-11:45 Break David Marsan Institute of Earth Science, University of Savoy 11:45-12:15 Earthquakes promoted by aseismic deformation: seismic hazard implications Depart. Civil & Environmental Engineering, Jeffrey W. Berman University of Washington 12:15-12:45 Simulation of structural response and tsunami impacts for Magnitude 9 Cascadia Subduction Zone Earthquakes 12:45-14:00 Lunch Break Afternoon Session Chair: Hiroaki Kato, Tomomi Kito Institute for Radiological Protection Marie Simon-Cornu 14:00-14:30 and Nuclear Safety Some insights into post-accidental radioecology School of Community & Regional Planning, Stephanie Chang 14:30-15:00 University of British Columbia Modeling societal impacts of disasters: Progress and challenges 15:00-15:15 Break Steve New Saїd Business School, University of Oxford 15:15-15:45 Supply network resilience: A review and a critique of recent research Faculty of Economics & Business, University Dirk Pieter van Donk 15:45-16:15 of Groningen Building resilient supply chains: the role of supply chain integration

73 Morning Session Chair: Bogdan Enescu, Tomomi Kito Faculty of Life and Environmental Sciences, Yuji Yagi University of Tsukuba 9:15-09:45 MegaQuake Risk Management Project: A comprehensive approach towards mitigating earthquake-related disasters Faculty of Life and Environmental Sciences, Hiroaki Kato University of Tsukuba 9:45-10:15 Radiocesium transfer and ambient dose rate in Japanese forest environment following the Fukushima accident 10:15-10:30 Break Kyosuke Nagata President, University of Tsukuba 10:30-10:35 Greetings Director General, Secretariat of Japan Noriko Suzuki 10:35-11:05 Disaster Relief Team, JICA JICA’s Emergency Disaster Relief Faculty of Engineering, Information and Tomomi Kito Systems, University of Tsukuba 11:05-11:35 Supply network resilience: individual-level survivability vs network-level sustainability Faculty of Engineering, Information and Gaku Shoji Systems, University of Tsukuba 11:35-12:05 Damage assessment of infrastructures subjected to the 2011 off the Pacifi c coast of Tohoku earthquake and tsunami 12:05-13:10 Lunch Break Afternoon Session Chair: Shigehiro Fujino, Michitaka Umemoto, University of Tsukuba 13:10-15:00 Post-doctoral Researchers & Students Poster Presentations

15:00-15:20 Discussion among participants; remarks, suggestions for future cooperation

15:20-15:50 Student Poster Awards, Concluding remarks Morning, Afternoon Visit to areas affected by the 2011 M9.0 Tohoku-oki earthquake and tsunami. Planned departure from Tsukuba around 9:00, return around 17:00. Details of the trip will be announced later.

74 7&8-1

Anticipating the next great earthquake in the American Pacifi c Northwest

John E. Vidale

Earth and Space Sciences Dept., University of Washington, Seattle, USA

A Cascadia earthquake of magnitude 9 (M9) would cause shaking, liquefaction, landslides and tsunamis from British Columbia to northern California. The resulting losses would include damaged buildings, bridges and lifelines, as well as thousands of human casualties. At the University of Washington, we have started the NSF-funded M9 project, which addresses scientifi c and engineering challenges in reducing this risk. The shared vision is to reduce the catastrophic risk of a Cascadia M9 earthquake through integrated advances in forecasting, warning and adaptive planning across the social, built and natural environments. The challenges start by assessing the range of distributions of fault motion and, therefore, the shaking and tsunamis that the Cascadia fault might generate. The project addresses factors not previously considered: the distribution and timing of energy release on the fault, the coherent variation of frequency content of fault motion with fault depth, and the 3D effects of the deep basins along Puget Sound - and will attempt to specify the uncertainty in the estimated motions, which is critical to probabilistic estimation of earthquake impact, including liquefaction, landslides, tsunamis and built infrastructure response. To inform the development and deployment of earthquake early warning in the U.S., the project includes interview and survey research on the potential effects of messages that provide just a few seconds or minutes of warning. With local communities and agency partners, the project will improve the utility of probabilistic information by comparing how stakeholders interpret (a) single “worst case” hazard scenarios and (b) multiple probabilistic scenarios, and how each type of scenario is then incorporated into community emergency preparedness and long-range planning. By anticipating probable events and responses over a range of timescales following an earthquake and using this to guide long-term systemic change before the next earthquake occurs, the M9 project will help prevent natural hazards from becoming disasters.

75 7&8-2

Earthquakes promoted by aseismic deformation: Seismic hazard implications

David Marsan1, Thomas Reverso1, Blandine Gardonio1, Michel Bouchon2, Agnès Helmstetter2, Bogdan Enescu3

1ISTerre, Université de Savoie Mont Blanc, France 2ISTerre, CNRS, France 3University of Tsukuba

Episodes of slow-slip (or “silent earthquakes”) are known to occur along subduction zones in many regions of the Earth; similar with the “traditional earthquakes” they release the strain accumulated at the plate interface. However, while the “traditional earthquakes” release the energy in seconds, a slow-slip event can last for days or weeks. Many of these slow-slip events can trigger anomalous earthquake activity, especially if they occur at shallower depths. One can detect a possible slow-slip event by searching for such anomalous seismicity patterns. Detecting and monitoring these slow-slip episodes is important for seismic hazard assessment, as they impact the slip budget, the stress surrounding faults, and therefore the generation process of large megathrust earthquakes; they also indicate areas of low to moderate tectonic coupling. This talk will present recent fi ndings related to earthquake swarms likely triggered (caused) by slow-slip in subduction zones. Using seismicity data, one can detect and characterize such transient deformation episodes, and sometimes even estimate the total slip accommodated by slow-slip events that have escaped detection by geodetic measurements. Note that due to lack of nearby geodetic measurements, slow-slip events , in particular smaller ones, may often escape detection. This is also the case of the s low-slip events that occurred at Boso Peninsula prior to 1990. Moreover, very large interplate earthquakes, including the 2011 Tohoku-oki megathrust event, can be preceded by migrating slow-slip, possibly resulting from a large-scale deformation of the slab, down to large depths (~ 100 km). Although these seismicity patterns may also occur in the absence of impending large shocks, scientists hope that by combining various types of geophysical information, they will better understand the preparation processes of megathrust earthquakes and thus contribute to a better seismic hazard assessment.

76 7&8-3

Simulation of structural response and tsunami impacts for Magnitude 9 Cascadia Subduction Zone Earthquakes

Jeffrey Berman1, Nasser Marafi 1, Marc Eberhard1, Michael Motley1, Randall LeVeque2, Frank Gonzalez3

1Department of Civil and Environmental Engineering, University of Washington 2Department of Applied Mathematics, University of Washington 3Department of Earth and Space Sciences, University of Washington

With support from the U.S. National Science Foundation, an interdisciplinary team is investigating the likely impacts of Magnitude 9 Cascadia Subduction Zone (CSZ) earthquakes. This talk highlights preliminary results investigating structural response, tsunami generation and tsunami structural impacts. The research uses ground motions and fault displacements generated by the seismology part of the team and derived from an extensive 3D fi nite difference model of the regional geology. A new seismic intensity measure that combines spectral shape and duration and correlates well with structural collapse is presented and was developed to better characterize the unique ground motions generated from the CSZ. The structural response of key representative buildings is also presented as a starting point towards broad regional response evaluation. In conjunction with the seismic risk in the Cascadia region, there is signifi cant tsunami risk to the Pacifi c Coast and recent storm surge events across the United States have shown a potential for consequences to domestic infrastructure similar to what was seen in East Asia and the Pacifi c. Interest in tsunami load predictions for structural design has grown, but it is diffi cult to develop models that accurately predict the tsunami load response of an individual structure, much less the tsunami risk for multiple structures within a specifi c region. The M9 team is developing a multiscale, probabilistic framework for predicting the fl uid loading and structural response of coastal structures at a community level. These developments are essential for bridging the gap between computationally practical simulation techniques and high-fi delity numerical models and will provide numerical tools specifi cally designed for improving the safety and resilience of coastal communities.

77 7&8-4

Some insights into post-accidental radioecology

Marie Simon-Cornu

Institut de Radioprotection et de Sûreté Nucléaire, PRP-ENV, SERIS, LM2E, Cadarache, France

As a research and expert appraisal organization, the French Institute for Radiation Protection and Nuclear Safety (IRSN) contributes to the implementation of public policies concerning nuclear safety and security, and health and environmental protection against ionizing radiation. This general statement will be illustrated in this talk in the context of the consequences of a natural disaster. The safety of any nuclear installation (reactor, plant, storage, research centre) must be ensured, even in the event of external hazards, such as an earthquake on the site. Thus, seismic risk must be incorporated in the design calculations for installations. IRSN performs research and carries out assessments in this fi eld but this will not be the focus of this talk. Despite all precautions taken, the hypothesis of an accident in a nuclear installation can , nevertheless, never been excluded. When such an accident leads to the release of radioactive pollutants in the environment, they may contaminate all media, and expose ecosystems and populations. The study of the transfer of these pollutants in the environment, and the assessment of the consequences on humans and environment is called radioecology. IRSN also performs research and carries out assessments in this fi eld. Radioecology will be the main focus of this talk through the example of an on-going research project: AMORAD (Improvement of dispersion forecast models and impact assessment of radionuclides in the environment). This project (2013-2019), led by IRSN with 12 partners, including University of Tsukuba, aims to answer the central question, “How can the consequences of a release of radioactive substances on humans and the environment be more accurately assessed?” The AMORAD project studies the major biosphere compartments – sea, land and interfaces - in order to relevantly treat fl uxes between them. “Workshop areas” are located in various places, in France, in Chernobyl, and in Japan, in the regions contaminated after the Fukushima accident.

78 7&8-5

Modeling societal impacts of earthquakes: Progress and challenges

Stephanie E. Chang

School of Community and Regional Planning (SCARP) and Institute for Resources, Environment and Sustainability (IRES), University of British Columbia

In recent decades, considerable progress has been made in understanding the societal impacts of earthquakes. Earthquakes cause a broad range of interrelated consequences to society, including not only human casualties and the costs to repair damaged buildings and infrastructure, but also displacement of people from their homes, psychosocial impacts, and economic disruption to businesses. As understanding of how earthquakes impact society becomes more sophisticated, researchers have tried to capture these impact mechanisms in computational models in order to depict what can be expected in future earthquakes. This allows researchers to study how those expected impacts might differ depending upon what societal decisions are undertaken; for example, regarding seismic retrofi t policies, preparedness planning, or long-term urban development. Ultimately, it is hoped that such models will help support decision-making regarding seismic risk reduction. This presentation provides an overview of progress in modeling societal impacts of earthquakes. It focuses on several key topics: economic or business disruption impacts, lifeline infrastructure impacts, transportation impacts, recovery, and the underlying dynamics of the urban context. In each of these areas, progress has been made in modeling approaches, but challenges remain and new research needs have emerged. These challenges and research needs are illustrated with examples from Canadian models, as well as lessons from recent earthquake disasters.

79 7&8-6

Supply network resilience: A review and a critique of recent research

Steve New1 and Tomomi Kito2

1Saïd Business School, University of Oxford 2Faculty of Engineering, Information and Systems, University of Tsukuba

Recent years have seen an explosion of research on the subject of supply network resilience. This has been in part driven by the experiences following the 2011 Tohoku earthquake and tsunami, and in part by increasing concerns with the vulnerability of global supply chains to threats from international terrorism. In particular, many researchers have sought to establish the connection between supply network morphology and resilience, asking the question: are some network structures more resilient than others? In this review, we present a critique of this work, establishing four principles for understanding supply network resilience. Firstly, we demonstrate that system-level catastrophes require system-level resilience: we show how this is a fundamentally different question to handling individual node or link failures. Second, we emphasise the way in which morphological structure needs to be complemented with other information to produce meaningful analyses. Third, we illustrate how strategies for problem avoidance contrast with strategies for problem recovery. Finally, we demonstrate how network modelling might be useful for understanding incremental rather than catastrophic network failure.

80 7&8-7

Building resilient supply chains: The role of supply chain integration

Dirk Pieter van Donk

Department of Operations, University of Groningen, Groningen, The Netherlands

A supply chain (SC) will be affected in its performance if one of its links suffers from a disruption. Supply chain resilience aims at dealing with disruptions and can be defi ned as “the adaptive capability of the supply chain to prepare for unexpected events, respond to disruptions, and recover from them by maintaining continuity of operations at the desired level of connectedness and control over structure and function” (Ponomorov & Holcomb, 2009, p. 131). While SC resilience is important in case of unexpected events, it is obvious that SC integration is pivotal in realizing and maintaining an effi cient and effective operating supply chain under normal conditions. On the one hand it has been claimed that integrated chains are more vulnerable as a disrupted link will propagate throughout the entire network. On the other hand, the opposite has been stated, as tightly coupled chains might be better fi tted to react and recover. So far, previous empirical research regarding the effect of supply chain integration on resilience has been inconclusive with respect to these arguments as it shows contrasting fi ndings (Braunscheidel and Suresh, 2009; Paulraj and Chen, 2007; Wieland and Wallenburg, 2013). The present study aims to better understand the relationship between SC integration and SC resilience. The empirical base is the International Manufacturing Strategy Survey (IMSS) VI, which is a sample of 931 fi rms from 22 countries, complemented with qualitative data from recently conducted explorative cases to better understand how SC resilience and SC integration relate and interact. The explorations are part of a larger research project “Enhancing resilience while maintaining effi ciency: planning and human decision-making for the unpredictable” that integrates organizational behavior and supply chain management knowledge to contribute to the emerging fi eld of supply chain resilience.

81 7&8-8

MegaQuake Risk Management Project: A comprehensive approach towards mitigating earthquake-related disasters

Yuji Yagi

Faculty of Life and Environmental Sciences, University of Tsukuba

The March 11, 2011 Tohoku-oki earthquake (M9.0) caused unprecedented damage along the coastal areas of Tohoku and Kanto regions of eastern Japan. While the megathrust earthquake represents the triggering factor of the subsequent disaster, the chain-mechanism of the associated damage is complex and its understanding requires the collaboration of specialists from multiple disciplines. In order to reduce as much as possible the unexpected associated with future megathrust earthquakes, it is necessary to develop a new inter-disciplinary approach that fi lls the gaps between different research fi elds. Professionals with various scientifi c and technical expertise should work together with the local and regional administration for a more effective risk assessment and mitigation. After the Tohoku-oki earthquake, the University of Tsukuba started up the MegaQuake Risk Management Project. The present project represents a collaborative effort between the University of Tsukuba and several research institutions located in the Tsukuba Science City towards an effective mitigation of risks associated with the occurrence of large and giant earthquakes. Assuming as a case-study the occurrence of a massive earthquake off the coast of Ibaraki Prefecture, the project aims of creating scenarios and measures based on the latest research fi ndings that will be used in making informed recommendations to the local governments in Ibaraki prefecture. There are six research groups participating in the project: (G1) Mega-earthquakes and tsunamis, (G2) Strong motion, tsunami and landslides, (G3) Damage to civil infrastructures, (G4) Environmental issues and long-term disasters, (G5) Human behavior and social impact associated with complex disasters, (G6) Urban and Regional Planning and Reconstruction. The topics covered span various complementary fi elds related to disaster assessment and mitigation. In my presentation, I will introduce the outline and outcomes of our project.

82 7&8-9

Radiocesium transfer and ambient dose rate in Japanese forest environment following the Fukushima accident

Hiroaki Kato

Faculty of Life and Environmental Sciences, University of Tsukuba

We investigated the transfer of canopy-intercepted radiocesium to the forest fl oor for three years following t he Fukushima Daiichi Nuclear Power Plant accident. The cesium-137 (Cs- 137) contents in throughfall, stemfl ow, and litterfall were monitored in two coniferous stands (plantation of Japanese cedar) and a deciduous broad-leaved forest stand (Japanese oak with red pine). We also measured the ambient dose rate (ADR) at different heights in the forest using a survey meter and a portable Ge gamma-ray detector. Total Cs-137 deposition fl ux from the canopy to forest fl oor for the mature cedar, young cedar, and the mixed broad-leaved stands were 166 kBq/m2, 174 kBq/m2, and 60 kBq/m2, respectively. These values correspond to 38%, 40% and 13% of total atmospheric input after the accident. The ambient dose rate in forest exhibited height dependency and its vertical distribution varied with forest type and stand age. The ambient dose rate showed an exponential decrease with time for all the forest sites, however the decreasing trend differed depending on the height of dose measurement and forest type. The ambient dose rate at the canopy (approx. 10 m-height) decreased faster than that expected from physical decay of the two radiocesium isotopes, whereas those at the forest fl oor varied between the three forest stands. The radiocesium deposition via throughfall seemed to increase ambient dose rate during the fi rst 200 days after the accident, however there was no clear relationship between litterfall and ambient dose rate since 400 days after the accident. These data suggested that the ambient dose rate in forest environment varied both spatially and temporally refl ecting the transfer of radiocesium from canopy to forest fl oor. However, further monitoring investigation and analysis are required to determine the effect of litterfall on long-term trend of ambient dose rate in forest environments.

83 7&8-10

JICA’s Emergency Disaster Relief

Noriko Suzuki

Director General, Secretariat of Japan Disaster Relief Team, Japan International Cooperation Agency (JICA)

In spite of countless and continuous disaster-preparedness efforts being made everywhere in the world, natural or man-made disasters still threaten people’s lives anytime and anywhere. Japan is prone to natural calamities, and we have expertise in taking responses to disasters and are thus committed to assisting the victims of such disasters wherever they may occur, making the most of our experience. Japan International Cooperation Agency (JICA) is responsible for administering Japan’s disaster relief operations in response to requests from any affected government or international organization following natural or man-made disasters. JICA offers a variety of Japan Disaster Relief (JDR) Teams, which consist of rescue teams, medical teams, expert teams, and the Japan Self Defense Force Units, dispatching either alone or in combination to meet the needs of disaster-affected areas. When a large-scale disaster occurs, overseas and affected country or an international organization requests the Ministry of Foreign Affairs (MOFA) to provide assistance, and MOFA deems it appropriate to dispatch a JDR Team, it will consult with the other ministries and agencies concerned for obtaining cooperation in dispatching a JDR Team. JICA is responsible for conducting the dispatch and other necessary tasks following the decision of MOFA Apart from the JDR Teams, JICA also sends emergency relief goods to these areas as required. To facilitate the rapid and reliable provision of a large volume of the goods, reserve supplies must be procured and properly stockpiled well in advance at locations as close as possible to disaster-prone areas. JICA stores these goods at warehouses overseas: Singapore, Miami, and Dubai. Emergency disaster relief should be well coordinated among various humanitarian actors in order to avoid the burden of affected countries and to increase the effectiveness of assistance. JICA is actively contributing to coordination efforts lead by UNOCHA at the time of extending its assistance.

84 7&8 Postdoctoral Researchers & Students Poster Presentations - Abstracts

7&8 Postdoctoral Researchers & Students Poster Presentations - Abstracts

85 7&8-11

Supply network resilience: Individual-level survivability vs. network-level sustainability

Tomomi Kito1 and Steve New2

1Faculty of Engineering, Information and Systems, University of Tsukuba 2Saïd Business School, University of Oxford

This study quantitatively investigates the dynamic and heterogeneous nature of the structures and characteristics of real-life automobile parts supply networks, through complex network analysis of empirical data. Under situations with various possible risks such as economic crises and market globalization, supplier fi rms must both work together for sustainable production, and also compete with each other for their own survival. At the individual (microscopic) level, each fi rm strategically builds its own product portfolio (the line of products it makes), according to its capability/resource limit, fi nancial dependencies on other fi rms, and the market situation. The network-level (macroscopic) resilience/sustainability of a given supply network then needs to be captured as the result of emergence, through a multiplicity of repetitive decision-making a nd interactions of such heterogeneous fi rms. Comprehensive longitudinal data we collected contains information of ‘who-supplies- what- to-whom’ in the Japanese automobile industry, and successfully highlights the wide diversity of fi rms’ strategies and product characteristics. We fi rst focus on supply networks of various different products; by applying a metric called ‘nestedness’, we demonstrate how various factors such as the level of product standardization and technological advancement may result in the heterogeneity of the network structures and their temporal transitions. We then shift our focus on fi rms’ strategies; instead of looking at supply relationships between fi rms for each product, we project the set of information into another information space and create a new network that refl ects the strategic interconnectivity of products. By analyzing this ‘product-space’ network, we obtain insights into how various fi rms with different capabilities and strategies may be surviving by making certain combinations of products. This mesoscopic level analysis provides profound insights that can bridge the gap between the fi rm-level survivability and network-level sustainability. We hope this study and our future studies will contribute to the realization of more resilient industrial systems.

86 7&8-12

Damage assessment of infrastructures subjected to the 2011 off the Pacifi c coast of Tohoku earthquake and tsunami

Gaku Shoji

Faculty of Engineering, Information and Systems, University of Tsukuba

Infrastructures such as transportation facilities, water treatments, electric power and gas supply systems and telecommunication networks were severely damaged due to the 2011 off the Pacifi c coast of Tohoku earthquake and tsunami, and it caused malfunctions of our societal and economical activities. Based on the associated damage assessment by previous studies (Shoji G and Nakamura T., Journal of Disaster Research 9(2): 121-127, 2014, Tsukiji T and Shoji G., Safety, Reliability, Risk and Life-Cycle Performance of Structures & Infrastructures eds by G. Deodatis, B. R. Ellingwood and D. M. Frangopol, CRC Press Taylor & Francis Group, London: 2013, Shoji G et al., Journal of Disaster Research 7(sp):491-499, 2012, Shoji G et al., Applications of Statistics and Probability in Civil Engineering eds by M. H. Faber, J. Kőhler and K. Nishijima, Taylor & Francis Group, London: 1415-1423, 2011), big data on physical damage and functional disruption for road networks suffered by the tsunamis, sea walls during the surges, buried pipelines for water distribution systems, sewerage, and telecommunication networks by the ground excitation and liquefaction, and the electric power failures are quantitatively summarized in this presentation. Seismic and tsunami damage functions statistically modeled by the above damage real data are compared for understanding the novelty of the infrastructure damage in the 2011 Tohoku earthquake and tsunami, classifi ed as extreme complex seismic and tsunami disasters. Reasonable use of these damage functions for predicting the risks of infrastructures exposed by the Nankai megathrust earthquake and tsunami is also shown to implement academic research within reduction of the future extreme complex disasters.

87 7&8-13

Evaluation of wide-area landslide damage by depth-integrated particle method

Alessandra Mayumi Nakata and Takashi Matsushima

Department of Engineering Mechanics and Energy, University of Tsukuba

Landslides occur every year all over the world, and the mitigation of landslide-induced disaster is an urgent issue. The diffi culty in predicting landslides originates mainly from the lack of mechanical understanding and the lack of data on site. The former concerns the mechanical behavior of unsaturated surface soil and the rain water penetration through it, transition behavior of the soil from solid phase to liquid phase, and the fl ow behavior of soil-water-air mixture. The effect of vegetation on the mechanical behavior of surface soil should also be considered. The latter includes the detailed topographic data, the mechanical properties of surface soil and other components that differ in different places, and water content in the soil that changes not only spatially but also in time. In particular, the evaluation of landslide runout area requires the mechanical properties of the rapidly fl owing soil-water mixture, which are quite diffi cult to obtain before failure. In order to overcome such diffi culties, this paper deals with the procedure to predict damage area due to rainfall-induced landslides in a wide region using a depth-integrated particle method. Precise topographic data (Digital surface model, DSM) of the region is obtained from ALOS satellite images by stereo-photogrammetric method. Initial slope failures due to the increase of ground water level are detected by a conventional one-dimensional slope stability analysis. Then we adopt a depth-integrated particle method for the simulation of landslides to evaluate the downstream damage area. Considering the diffi culty in obtaining detailed material properties before disaster, the number of material parameters used in this evaluation procedure is limited as much as possible, which are soil density, the initial failure slope angle, if, Manning coeffi cient, n, for the fl owing soil-water mixture, and the critical slope angle, id, for the mixture to be deposited. We applied the procedure to the wide area (10km by 10km) in Rio de Janeiro, Brazil, which was severely damaged due to rainfall-induced landslides in 2011, to statistically validate the procedure. Full parametric study shows that the average of the accuracy of the damaged area prediction is

51% at maximum, when if = 19.7(deg), n = 0.08 to 0.1, id = 0 to 3(deg.). The value of if was found to correspond to the fully-saturated surface soil condition. The values of n and id are also reasonable from the literature. We also found that the damaged area predicted by the simulation includes old landslide scars, which implies that the predicted results may include the dangerous area for future landslides. The key issue is the statistical evaluation of the result. We cannot expect the perfect agreement between the actual damage and the result of the simulation based on such a simple numerical method as the proposed one. However, considering the uncertainty and the variation of the material parameters of natural slopes, the accuracy shown in this paper must be suffi cient for making hazard maps. Moreover, by accumulating the evaluation data in many other regions, we can classify the regions with the same material parameter set to further explore the correlation between such parameters and other information on geology, vegetation, climate, and so on.

88 7&8-14

Wave number and water depth of coastal area estimated from SAR satellite images

Shuhei Yukikawa1 and Satoshi Takewaka2

1Graduate Student, Department of Engineering Mechanics and Energy, Graduate School of Systems and information, University of Tsukuba 2Professor, Department of Engineering Mechanics and Energy, Graduate School of Systems and information, University of Tsukuba

In May 2014, SAR satellite ALOS-2 was launched by JAXA (Japan Aerospace Exploration Agency). SAR satellite emits microwave, measures back-scatter from the surface of the earth, and can observe data in a higher frequency than satellites sensing in visible range because it can gather data in land and sea areas during night and cloudy conditions. In this research, water depth distribution is estimated by analyzing wave number distribution captured in SAR images with dispersion relationship of water wave. We used images captured by SAR satellites ALOS (PALSAR) and ALOS-2 (PALSAR-2). Wave number distributions of wave fi elds of Kashima Coast, Japan, are estimated with Fourier analyses. Estimations of the wave number distribution of the wave fi eld show clearly the features of the wave refraction: wavelength becoming shorter if the waves approach the shoreline, and wave propagation changes its direction becoming parallel to the coast. Water depths were estimated with linear dispersion relationship, and compared with the surveyed data by the Maritime Safety Agency. Although there are discrepancies between the estimation and observation, overall trend of the water depth distribution are fairly well reproduced.

89 7&8-15

Shaking table test of wooden houses with several different building strength and input ground motion and seismic response analysis

Masashi Shiomitsu1 and Yuki Sakai2

1Graduate Student, Graduate School of Systems and Information, University of Tsukuba 2Faculty of Engineering, Systems and Information, University of Tsukuba

It is necessary to accurately estimate the building damage immediately after an earthquake occurs to reduce earthquake damage as much as possible. Although there are buildings with various strengths, building damage is also changed by the characteristics of ground motion. So, we conducted a shaking table test of wooden houses with different strengths and input ground motion. We used the JMA Furukawa record in the 2011 off-the-Pacifi c Coast of Tohoku Earthquake (during when the periods 1-1.5s which have close relationship with heavy damage to buildings are predominant), and the JMA Ofunato record in the 2003 Miyagiken-Oki Earthquake during the periods 0-0.5s which are predominant as input ground motion. As a result of JMA Furukawa, specimens deformed larger as the strength decreases, with some specimens almost collapsed. In the case of JMA Ofunato, deformation of all specimens was small, but the specimen with the highest strength deformed larger than under JMA Furukawa, useful result was obtained to examine the seismic intensity measure which determines maximum deformation of a building. We conducted seismic response analysis by modifi ed-Takeda-Slip model using single- degree-of-freedom system, it could accurately reproduce the experimental results. We also investigated the method to estimate the parameter of the model from standard shear force coeffi cient, with analysis showing that maximum deformation was less than the experimental results.

90 7&8-16

A method that makes JMA seismic intensity correspond to heavy damage to houses and buildings and its physical background

Mikito Kezuka1 and Yuki Sakai2

1Graduate Student, Graduate School of System and Information Engineering, University of Tsukuba 2Faculty of Engineering, Information and System, University of Tsukuba

It is important to estimate building damage quickly after an earthquake had occurred. JMA seismic intensity is well known, as it is calculated immediately after an earthquake occurrence in Japan. However, the intensity corresponding with bodily sensation does not mean buildings were damaged heavily. Therefore, we tried to modify the fi lter used in the calculation of JMA seismic intensity in order to correspond to the heavy damage using past large earthquake data. First, frequency characteristics of fi lter were modifi ed based on 1-2 second period that correspond to heavy damage to houses and buildings. Next, seismic intensity was reduced according to the duration of principal ground motion based on the data that building damage was small when the strong ground motion has long principal ground motion. As a result, we could calculate the seismic intensity corresponding to actual heavy damage to buildings and houses. In order to make this physical background clear, numerical experiments were done using sine waves ranging from short to long periods of a number of cycles and an envelope of sine wave. It became clear that building damage ratio changed by a combination of dominant period and a number of cycles when the strong ground motion have the same acceleration amplitude.

91 7&8-17

Examination of SSMA by 3D model numerical simulation

Kyosuke Yamamoto1 and Mikio Ishikawa2

1Faculty of System & Information, University of Tsukuba 2College of Engineering System, University of Tsukuba

Recently, the VRA (Vehicle Response Analysis) method for bridge damage detection has been intensively studied. To improve the accuracy of VRA, SSMA (Spatial Singular Mode Angle) has been proposed in the previous studies. SSMA is a ratio of amplitudes of the fi rst bridge mode shape estimated only by using data measured on a passing vehicle. In this meth- od, the sensors installed on the vehicle are only used. SSMA does not show the exact bridge mode shape. However, it is said that SSMA is effi cient to be used for VRA, because it is indi- cated that SSMA has high sensitivity to bridge local damages in the constant measuring condi- tion even before and after the bridge damage. Technical issues remain such as to analytically realize the mechanism on how SSMA detect bridge damage. In the previous studies, experiments on relationship between bridge damage and SSMA with a model and a real bridge were carried out. However, more SSMA data are necessary to show the availability of SSMA. Then, a numerical simulation of 2D model was carried out. However, 2D model is not enough to realize the mechanical properties of SSMA. Therefore, in this study, to research more detailed availability and mechanism of SSMA, numerical simulation of 3D model is carried out. 3D model of a truss bridge modeled by FEM (Finite Element Method) and a vehicle modeled by RBSM (Rigid Body Spring Model) are used. By changing conditions, such as road surface, vehicle speed, and damage location of the bridge, we check the change of SSMA and its mechanism.

92 7&8-18

Development of web application system for town-scale earthquake damage estimation

Yuta Takahashi1, Kyousuke Yamamoto2, and Yuki Sakai3

1College of Engineering System, University of Tsukuba 2,3Faculty of System & Information, University of Tsukuba

To control the risk of earthquake damage, the Japanese government is intensively promoting seismic retrofi tting as a hardware side of counterparts, while 20% of old buildings are still lower seismic resistant than required. Thus, to reduce the number of victims, a software side becomes more important. For example, a software program to estimate the city-scale damage has been developed to enable the government to deploy rescue units rapidly. However, the existing programs can estimate only damage-rate, and the results are not so open, or at least not friendly, for the public. Furthermore, those resolutions of the city are too low to assess the situation damage of each town and area. In this study, a new earthquake damage estimation system which can estimate detail damage-quantity has been developed. This program can monitor earthquake events, estimate the detailed situation damage of towns and areas by extracting the critical components against the structures from seismic waves, and show the estimation results on Google Map for easy understanding. The estimation of situation damage can be done in less than 30 minutes in most cases. However, it was not easily viewable, and some output data size of the system is too huge to display on mobile devices. In this study, as a more user-friendly system, the quick estimation method in which a user can see the situation damage around him/her on their own mobile device is constructed by using the user’s GPS information to reduce the estimated data size.

93 7&8-19

Risk assessment of road networks subjected to the Nankai Trough earthquake and tsunami

Yuta Mizukoshi1 and Gaku Shoji2

1College of Engineering Systems, University of Tsukuba 2Associate Professor, Faculty of Engineering, Information and Systems, University of Tsukuba

Risk assessment for predicting the damage of road networks due to the Nankai Trough earthquake and tsunami is strongly required. In previous studies, Nakamura and Shoji (Nakamura T and Shoji G., Journal of Japan Society of Civil Engineers A1 70(4): 210-218, 2014) calculated the time histories of the inundation depths at the bridges subjected to the 2011 earthquake and tsunami that originated off the Pacifi c coast of Tohoku, and revealed the features of tsunami waveforms needed for damage prediction of road networks in tsunami hazardous areas. However it has not been suffi ciently done by using their results. In this study, we estimated the damage ratio for road networks exposed by the Nankai Trough earthquake and tsunami. First, we improved the damage functions, which were modeled by Nakamura and Shoji (Nakamura T and Shoji G., Proceedings of the Second International Symposium on Earthquake Engineering 2: 239-242, 2013) for calculating the damage ratio of bridges due to the 2011 Tohoku earthquake and tsunami. Second, we revealed the time series data of the inundation depths at bridges in road networks exposed by the Nankai Trough earthquake and tsunami. We assumed three fault regions along the Nankai Trough: the fault regions from Suruga Bay to Kii Peninsula (Case1), from Shikoku-Oki to Kyushu-Oki (Case2), and from Aichi Prefecture-Oki to Mie Prefecture-Oki and Muroto Peninshura-Oki (Case3). Finally, we applied the time series data to damage functions and estimated the damage class of subject bridges in the exposed road networks. It was found that the values of damage ratio at the bridges vary in the lower range from 0.01 to 0.05 with the 87% occurrences of the 1.0 to 5.0 m inundation-depth interval with respect to all inundation-depth data for the Case1 assumption, and reach 0.20 and 0.25 respectively in the higher range with the 83% occurrences for the Case2 assumption and with the 82% occurrences for the Case3 assumption.

94 7&8-20

Estimation of seismic waveforms at engineering bedrocks beneath lifeline networks that suffered severe liquefaction during the 2011 Tohoku earthquake

Masahiro Hara1 and Gaku Shoji2

1College of Engineering Systems, University of Tsukuba 2Associate Professor, Faculty of Engineering, Information and Systems, University of Tsukuba

Lifeline networks such as water treatments, electric power supply systems and telecommunication systems were severely damaged due to the 2011 earthquake off the Pacifi c coast of Tohoku (hereinafter referred to as the 2011 Tohoku earthquake). Among previous studies associated with the above issues, Shoji et al. (Shoji G. et al., Applications of Statistics and Probability in Civil Engineering, Editors M. H. Faber, J. Kőhler and K. Nishijima, Taylor & Francis Group, London: 1415-1423, 2011) formulated seismic damage functions for buried sewer pipelines in Hitachinaka, Kamisu and Chiba cities (Ibaraki and Chiba Prefectures), where severe pipeline damage occurred due to strong ground motions and soil liquefaction. However, the physical damage mechanism responsible for those phenomena has not been explained enough, although the spatial distribution of damage ratios for lifeline networks was clarifi ed. The dynamic characteristics of the surface ground, in which pipelines are buried, need to be clarifi ed based on the analysis in terms of seismic wave properties, which induced vibration of the ground surface. Therefore, we simulated the propagation of seismic waveforms during the 2011 Tohoku earthquake with the source model of Yagi and Fukahata (Yagi Y. and Fukahata Y., Geophysical Research Letters 38:L19307, 2011), by applying the fi nite-difference method for simulating seismic waveforms with 4th-order spatial and 2nd- order temporal discretization. Synthetic velocity waveforms in engineering bedrocks beneath lifeline networks at Hitachinaka and Kamisu cities in Ibaraki Prefecture and Mihama District of Chiba City were estimated. We have also calculated the Fourier spectrums from the seismic waveforms. As a result, it was found that the predominant periods showed long-period components of about 50s and about 3s. These features caused the long-period vibration and liquefaction at a shallow layer above the engineering bedrocks.

95 7&8-21

A study on the relationship between land-use mixture and physical built environment

Sunyong Eom1 and Tsutomu Suzuki2

1Graduate School of Systems and Information Engineering, University of Tsukuba, University of Tsukuba 2Division of Policy and Planning Sciences, Faculty of Engineering, Information and Systems, University of Tsukuba

There are growing needs for measures to cope with urban problems such as decreasing population, increasing use of automobiles, decaying urban centers, and increasing infrastructure maintenance. There are, however, some discussions that current land-use planning system may not be able to cope with. In order to address these problems, the need for greater mixed land-use has been adopted as conventional wisdom among urban planners as well as public health professionals. Many studies have been conducted considering the relationship with transportation behavior, land price, and heath conditions, and they have argued that mixed land- use could contribute to a sustainable urban structure by reducing automobile use, enhancing non-vehicle activities, and vitalizing neighborhood environments. Another question that needs to be asked to support the concept of mixed land-use is how current land-uses are mixed, and how they associate with built environments and regulations. However, effective and suitable measures for mixed land-use and their effects are not necessarily clear, and the relationship between mixed use and physical environments, such as building density and road condition, is hardly considered. This study seeks to examine the current degree of mixed land-use and investigate the relationship with physical built environment by focusing on three types of spatial relationships among land-uses. For this purpose, fi rst, this study defi nes three kinds of mixed land-use indices; adjacency, proximity and intensity. Adjacency is defi ned as the length of perimeter divided by the square root of area. Proximity is calculated by the nearest distance between the target parcel and opponent parcel which have different land use. If an average value of proximity for all land-use is low, this parcel has a high degree of mixture in terms of proximity. Lastly, intensity is defi ned with the proportion of each land use which exists within infl uence distance from the target parcel. Second, degree of mixed land-use is investigated based on land-use data of Tokyo and Seoul. When we conducted a pre-analysis in several wards in Tokyo, industrial use showed the highest degree of mixture out of all indices. On the other hand, residential use showed a relatively low degree of mixture with the exception of the intensity index. Third, the relationship between the degree of mixed land- use and physical environments was investigated. In order to investigate whether degree of mixed land-use varies depending on physical built environment, mixed land-use indices are compared with built environments such as zoning regulation, building density, parcel density, and road networks. This study can give a clear understating for current level of mixed land- use and may contribute to future plans for accomplishing desirable mixed land-use structures.

96 7&8-22

A survey of the establishment of temporary local bus routes in the Great East Japan Earthquake and lessons learned from them: Focus on the Sendai Airport Limousine

Ryota Sato and Ayako Taniguchi

Department of Risk Engineering, Graduate school of System and Engineering, University of Tsukuba

Japanese society was heavily damaged by Great East Japan Earthquake on March 11, 2011. At the same time, public transportation systems were also heavily harmed. Although other public transportation systems, like railways and aviation, required several months for the restoration, local bus routes were restored at the very beginning. The reasons and stories of post-disaster restoration of local buses were investigated in this study. We interviewed persons responsible for local buses, such as local bus staff, staff of Ministry of Land Infrastructure Transport and Tourism (MLIT) and local governments by using the method of disaster ethnography, one of useful research methods for the disaster process analysis. The primarily aim of this study is to summarize and record the actions and emotions of people concerned with local buses from soon after the disaster to a month after the disaster. This study focused on the qualitative data to describe the establishment activity of the Sendai Airport Limousine, a temporarily established local bus route. This route was established owing to the government-led program aimed at connecting the Sendai Airport and Sendai Central Station. Our survey clarifi ed three most important factors that enabled the airport limousine to be established in a short period time: 1) top-down approach by MLIT, 2) bottom-up approach by the local bus company, 3) cooperation among government, bus association and bus company. On the other hand, our survey clarifi ed the abstruse confusions and diffi culties of the service construction, especially regarding the fi nancial and company selection problems. Consequently, the arrangement of the agreement between government and bus association could solve these problems by sharing common understanding among different associations and preparing preliminary measures for the disaster.

97 7&8-23

The effect of land-use/cover changes on urban waterlogging: A case of Changchun, China

Ma Donglai1, Norimitsu Ishii2, Yoshiaki Osawa1

1Department of Policy and Planning Sciences, Graduate School of Systems and Information Engineering, University of Tsukuba 2 Department of Housing and Urban Planning, Building Research Institute

This presentation took Changchun as an example and discussed the effect of land-use/ cover changes (LUCC) on urban waterlogging. The results showed that: 1) land-use/cover types have changed enormously in Changchun; 2) LUCC infl uenced the runoff change which can be described by the increase of runoff coeffi cient from the year 1995 to 2011; 3) when rainstorm intensity and catchment area did not change, the rain runoff in urban areas increased along with their development because of the expansion of impervious land surfaces. This warns us that those cities in China that have experienced rapid expansion are all in danger of serious waterlogging, and some have already become a terrible disaster. This research is useful for joint assessment, planning and management of city and water.

98 7&8-24

Extraction of evaluation factors on voluntary disaster prevention activities focused on their substantiation and durability

Ami Saito1 and Michitaka Umemoto2

1Master’s Program in Risk Engineering, Graduate School of Systems and Information Engineering, University of Tsukuba 2Faculty of Engineering, Information and Systems, University of Tsukuba

Since the 1995 Hanshin-Awaji earthquake (known also as the Kobe earthquake), the importance of self-help/mutual assistance has become increasingly important. In addition, the formation of voluntary organizations that can take part in disaster prevention activities has become a pressing issue all over Japan. There are many reports of such disaster-related activities, as they have been witnessed during the 2011 Great East Japan earthquake. Despite of sustained effor ts, various problems were pointed out, such as the heavy burden on organizations’ offi cials, the activities losing clear focus and so on. Most of the past studies focused on organizations’ activities that were analyzed based on formalized questionnaires. Therefore, it is partly unknown how much power voluntary organizations can show during a real disaster. Essentially, we consider necessary to clarify the reasons behind problems encountered during various activities and to understand which method is effective in appropriately estimating the performed activities. Thus, in order to comprehensively understand the underlying problems as well as the principal factors that could promote the activities of voluntary organizations, we conducted several interviews with their leaders and fi re station offi cers in the Tokyo metropolitan area. We focused on the substantiation and durability of each activity, extracted the most important factors from leaders’ comments and structured them by applying the KJ method. Our results show that there are some important issues to consider when aiming to encourage voluntary disaster prevention activities, such as lifelong learning as well as women and youth participation in such organizations.

99 7&8-25

Research on the obstructive factors of residents’ evacuation in heavy rain disasters

Kousuke Tanaka1 and Michitaka Umemoto2

1College of Policy and Planning Sciences, School of Science and Engineering, University of Tsukuba 2Faculty of Engineering, Information and Systems, University of Tsukuba

In heavy rain disasters, early evacuation is the most important thing for residents to do. However, not all of them tend to evacuate in actual disasters, and it results in huge damages due to fl oods or some kinds of sediment-related disasters. This situation would be caused by some factors related to residents, for example, non-receipt of accurate information about the coming rain, and their optimism of safety. Considering that there are some factors which prevent residents from evacuating in actual heavy rain disasters, we aimed in this paper to arrange these factors systematically to fi nd out how to promote evacuation. Most previous research papers about evacuation in heavy rain disasters dealt with an actual specifi c disaster case and concluded each knowledge separately. Through collecting papers published to date about evacuation in heavy rain disasters and organizing the data, we found the obstructive factors to evacuation behavior. We read 122 papers that dealt with the disasters which occurred after the 1982 Nagasaki Flood Disaster, and recorded the outlines and features of each evacuation case. After collecting these data, we arranged them by the KJ method and investigated obstructive factors that exist in the decision process of evacuation in heavy rain disasters from various aspects. Based on the results, through examining feasibility of the policies to promote residents’ evacuation and implementing them, it is hoped that residents get to evacuate more adequately.

100 7&8-26

Initial activities of volunteer fi refi ghters in coastal areas after a big earthquake: A study on Numazu City, Shizuoka

Yuta Suzuki1 and Eiichi Itoigawa2

1College of Policy and Planning Sciences, University of Tsukuba 2Faculty of Engineering, Information and System, University of Tsukuba

On March 11, 2011, the Great East Japan Earthquake occurred (hereinafter, “the 3.11 disaster”). The tsunami triggered by the 3.11 disaster caused unprecedented damage to a wide range of coastal areas, and about 20,000 people died or went missing. In each coastal area, members of the volunteer fi re department carried on various activities such as closing sluices, evacuation support, fi refi ghting, rescue, and more. However, by failing to evacuate from the tsunami, many volunteer fi refi ghters died or went missing themselves. Similarly, a large tsunami arriving faster than the 3.11 disaster is expected in case of a big earthquake along the Nankai Trough in southeast Japan. Moreover, while the number of volunteer fi refi ghters is decreasing, effective activities of a limited number will be required. Therefore, we need strategic planning for effective activities of volunteer fi refi ghters under the restrictions of limited time and number of members. As preparation for planning this strategy, we analyzed the fl ow of initial activities and the factors of implementation, continuation and stopping of activities of volunteer fi refi ghters based on the interviews with the volunteer fi refi ghters in Numazu City, Shizuoka Prefecture, where the Nankai Trough is located. As the fi rst of initial activities, the volunteers have to secure themselves and their family, then they gather in the Tsumesho or Tonjo which is the fi re department’s volunteer station to conduct their activities. Based on the experiences of the 3.11 disaster, the following have been pointed out: (1) A volunteer fi refi ghter estimates the time period to reach a safe place from the arriving tsunami in order to secure his safety. (2) A volunteer fi refi ghter may evacuate immediately without initial activities in order to prepare for fi refi ghting and rescue, after the tsunami had passed.

101 7&8-27

Radioactive Cs-137 discharge from headwater forested catchment in Fukushima after the Fukushima Dai-ichi Nuclear Power Plant accident

Sho Iwagami1, Yuichi Onda1, Maki Tsujimura2, Koichi Sakakibara3, and Ryohei Konuma3

1Center for Research in Isotopes and Environmental Dynamics, University of Tsukuba 2Department of Sustainable Environmental Studies, Graduate School of Life and Environmental Sciences, University of Tsukuba 3Department of Geoenvironmental Sciences, Graduate School of Life and Environmental Sciences, University of Tsukuba

Radiocesium migration from headwater forested area is important information as the output from the forest which is input to the subsequent various land use and downstream rivers. It is important to know the composition of radiocesium form (dissolved, suspended sediment or coarse organic matter) as it migrates through the headwater stream. In this study Cs-137 discharged by suspended sediment and coarse organic matter from headwater catchment were monitored. The Cs-137 concentration of dissolved water, suspended sediment and coarse organic matter such as leaves and branches and their amount were measured at stream site in three headwater catchments in Yamakiya district, located ~35 km north west of Fukushima Dai-ichi Nuclear Power Plant (FDNPP) from August 2012 to December 2014 (dissolved: from June 2011 to December 2014), after the earthquake and tsunami disaster. Declining trend and temporary increase of dissolved Cs-137 during the rainfall event are observed in dissolved water. Suspended sediment and coarse organic matter were sampled at intervals of approximately 1-2 months. The Cs-137 concentration of suspended sediment and coarse organic matter were 170-49000 Bq/kg and 350-14000 Bq/kg, respectively. The Cs-137 concentration of suspended sediment showed a positive correlation with average deposition density of catchment. The effect of decontamination works appeared in the decline of Cs- 137 concentration in suspended sediment. Contribution rate of Cs-137 discharge amount by suspended sediment was 96-99% during a year. Total annual Cs-137 discharge from the catchment was 0.02-0.3% of the deposition.

102 7&8-28

The estimation of 137Cs inventory and airdose rate around FDNPP using USLE

Noriko Nakamura1, Yoshifumi Wakiyama2, and Yuichi Onda1

1Center for Research in Isotopes and Environmental Dynamics, University of Tsukuba 2Institute of Environmental Radioactivity, Fukushima University

Due to the Fukushima Nuclear Power Plant accident in the East Japan great earthquake disaster, large quantities of radioactive material including radioactive cesium and radioactive iodine fl owed out into the area coming from the Fukushima Nuclear Power Plant. Most radioactives deposited in the soil still remain in Fukushima Prefecture. In this study, estimation of the time variation of the caesium-137 inventory around the Fukushima Nuclear Power Plant using the USLE model was attempted. Furthermore, the airdose rate around the nuclear power plant was estimated based on the calculated soil discharge and Cs-137 inventory. The calculation coeffi cients of the USLE model were determined by the observation result in the experimental fi eld. The calculation area includes within 80km circle of Fukushima Nuclear Power Plant and around the Abukuma River basin. We divided all domains to a 25m square cell, with soil discharge per cell calculated. Soil discharge from the paddy fi elds surrounded by the Abukuma River basin, and the quantity of annual soil erosion distribution from November 2012 to October 2013 provided local observation results. The amount of the soil discharge for each basin almost agrees with the observed value. In addition, the discharge of cesium-137 from March 2011 to October 2013 was estimated. The tendency that the cesium-137 discharge in the Abukuma River basin, where the paddy fi elds are relatively large, became high as well as the soil discharge. There was predominantly large discharge from paddy fi elds, and the outfl ow ratio decreased year by year. This corresponded to a local observation result. Furthermore, air dose rate around the nuclear power plant of October 2013 based on the above-mentioned result, was more accurate than a predictive dose rate, that soil erosion was not considered.

103 7&8-29

Modeling the 137Cs leaching dynamic from evergreen canopies after a radiocesium deposit

Nicolas Loffredo1, Yuichi Onda1, Pierre Hurtevent2 and Frederic Coppin2

1Center for Research in Isotopes and Environmental Dynamics, University of Tsukuba 2Institute for Radioprotection and Nuclear Safety, Cadarache, Saint Paul lez Durance, France

In the context of the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident, we focused on 137Cs fl uxes within throughfall where the main radiocesium water fl ux from canopy to the ground can be modeled by an Improved Double Exponential (IDE) equation. This -1 -1 equation used three groups of parameters: kinetic of leaching (k1; d and k2; d ), leachable 2 2 canopy inventory (A1; Bq.m and A2; Bq.m ), and rainfall (rf), and gave a good description of 137Cs leaching from cedar and broad leaf canopies. Except for the rf parameter, this equation did not account for any measurable environmental parameters. The parameters are adjusted to fi t 137Cs leaching calculated by the IDE equation, with existing 137Cs leaching data making the predictions of 137Cs leaching dynamics diffi cult if the Cs fl uxes from canopies to the ground are not measured. This study was therefore updated by integrating some physical measurable parameters into the IDE equation. Based on 14 throughfall monitoring collectors, the following parameters of the IDE equation were obtained: k1 and k2 (5.0E-04 d-1, 1.2E-02 d-1). The IDE model was used with other data sets from literature for different evergreen species (spruce and cypress) and we concluded that the kinetic parameters were the same whatever the evergreen tree species; We therefore concluded that there is no spatial variability concerning the kinetic of leachable 137Cs loss from evergreen canopies after a deposit, likely due to a common leaching mechanism such as weathering. In contrast, a high spatial variability has been observed for the total leachable stock (A1+A 2) that can be directly linked to the initial deposit and to canopy closure. The leachable stock follows a simple exponential law with canopy closure (CC) as a parameter. We therefore have included the CC in the IDE equation to calculate the total leachable 137Cs stock of the IDE equation.

104 7&8-30

Temporal changes of radiocesium in the irrigation water-soil- rice plant system after the Fukushima Daiichi Nuclear Power Plant accident

Baolu Yang1,2 and Yuichi Onda2

1Institute of Agro-products Processing Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 2Center fo r Research in Isotopes and Environmental Dynamics, University of Tsukuba

Rice paddies as the dominant agricultural land in Fukushima Prefecture, which are about half of the total paddy fi elds area, were contaminated by radiocesium due to the Fukushima Daiichi Nuclear Power Plant accident. In order to get a better understanding of the behavior of radiocesium in the paddy fi elds and to evaluate its health risk, two adjacent rice paddies were established to study the radiocesium dynamics in the irrigation water-soil-rice plant system during the years after the nuclear accident. One was a normal paddy where the surface soil was not removed and the other one was decontaminated paddy where approximately 96% of fallout radiocesium was eliminated via surface soil removal practice. The results showed that there was no signifi cant decrease of total radiocesium inventory in paddy soil after the nuclear accident. On the contrar y, it increased in 2012 and 2013 in both paddies. We further investigated the newly added radiocesium to paddy fi elds via irrigation water, which only contributed maximum 0.15% and 0.75% of the total amount present in soils for the normal paddy and the decontaminated paddy, respectively. The 137Cs and 134Cs concentration in suspended sediment in irrigation water can be described with exponential function and its effective half-life (Teff) for 137Cs and 134Cs was 1.3 and 0.9 years, respectively. The radiocesium accumulation in rice plant decreased with time in both paddies. However, though the radiocesium concentrations and inventory in soil were ten times lower in the decontaminated paddy than in the normal paddy, there was no signifi cant difference about radiocesium concentrations in rice and straw between the two paddies. Moreover, even the transfer factor of radiocesium in the decontaminated paddy was higher in the decontaminated paddy than in the normal paddy.

105 7&8-31

Mid-Late Holocene relative sea level changes and crustal movements due to the past Nankai earthquakes in Tainohama, Tokushima Prefecture, Japan

Takashi Chiba

Faculty of Life and Environmental Sciences, University of Tsukuba

In order to reveal tectonic movements of the earthquakes that occurred along the Nankai Trough, fossil diatom analysis was conducted on 700 cm long sediment core samples drilled at Tainohama marsh, Tokushima prefecture, Japan. More than 20 sand layers were recognized in organic muddy and peaty sedimentary succession up to 700 cm long in the core. The diatom assemblages characterized by freshwater and freshwater - brackish species from the organic rich muddy and peaty sediments and radiocarbon ages indicate that freshwater marsh or salt marsh formed in this area, at least during the last 5, 600 years. On the other hand, the sand layers include the diatoms living in environments where salinities are higher than salt marsh, so the assemblages suggest that the sand layers were transported from seaside by past tsunamis. Moreover, changes of diatom species in the organic or peaty mud sediments show fl uctuations of freshwater or freshwater-brackish diatoms and a gradual increase of freshwater species from bottom to top of the core, suggesting decadal and millennial scale paleo-sea level changes. Because of the eustatic sea level change during the mid-late Holocene, the sea level in this area gradually declined from +1.0 m higher than present to the modern sea level, therefore the millennial scale changes of diatoms refl ected the eustatic sea level changes. On the other hand, the decadal fl uctuations of freshwater species suggest co-seismic subsidence or inter- seismic uplift by the past interplate earthquakes along the Nankai Trough. In addition, deferent patterns from the co-seismic or inter-seismic crustal movements were recognized especially around 600, 2000, 3400, 4000 and 5600 years ago. Just before these events, brackish or marine species increased, so the sea level rose slightly in this area before these events. It may suggest these were pre-seismic subsidence.

106 7&8-32

Organic geochemical signatures associated with the 2011 Tohoku-oki tsunami

Tetsuya Shinozaki1,2

1Graduate School of Life and Environmental Sciences, University of Tsukuba 2Geological Survey of Japan, National Institute of Advanced Industrial Science and Technology

A correct understanding of tsunami events is important to predict their magnitude, frequency, and timing. Because tsunamis occur infrequently, current observational data for modern tsunamis are not suffi cient for a comprehensive understanding of these events. Analysis of historical and prehistoric tsunamis is therefore required. Sandy tsunami deposits have generally been used for paleotsunami research. Geological and micropaleontological features have frequently been utilized as identifying proxies. However, these characteristic features are not always preserved, in which case it can be diffi cult to identify paleotsunami deposits. If evidence of seawater inundation could be detected, it would be a good criterion for determining that sandy deposits have a marine source. Chemical proxies have been used as indicators of seawater. However, there is still little known about such geochemical characteristics; what kind of chemical components are transported onto the coastal land, and how long such a chemical component lasts. To determine how and what kind of biomarkers are preserved on land by tsunami, samples of the 2011 Tohoku-oki tsunami deposit and underlying and overlying soil were collected at Sendai, Odaka, and Hasunuma, East Japan. Molecular fossil biomarkers originating from living organisms play the role of tracers for the particular processes or sources of fl ora or fauna from which they were produced. From the results of above three areas, I propose that preservation potential of tsunami-derived biomarkers depend on depositional environments. It seems they are usually preserved in organic silty mud rather than sand. Biomarkers may possibly be preserved for long time. The fi ndings show the potential of using biomarkers as proxies for identifying marine-originated deposits on coastal land. For further applications (e.g., research into paleotsunami), more case studies of modern tsunamis and paleotsunamis are required.

107 7&8-33

Sedimentology of the 2011 Tohoku-oki tsunami deposits

Masaki Yamada

Graduate School of Life and Environmental Sciences, University of Tsukuba

The 2011 Tohoku-oki tsunami inundated a wide range of the lowlands, and transported v a r io u s d e p o sit s i n clu d i n g mu d - t o b o u ld e r- si z e d s e d i m e nt s t o i n l a n d f r o m s e a s h o r e. C a s e s t u d ie s of modern tsunami deposits provide us useful information to identify paleo-tsunami deposits in geologic strata. In this presentation, we discuss the effect of the difference in tsunami sizes and geomorphic characteristics on sedimentation and sedimentary characteristics of tsunami deposits. The height of the 2011 Tohoku-oki tsunami reached up to 28.1 m above sea level and inundated up to 1.8 km inland in Miyako City, Iwate prefecture. Tsunami deposits were composed of pebbles and cobbles near shore, whereas they were composed of sand and mud near the inundation limit, showing general trend of fi ning toward the inland. The thicknesses of the deposits were 1 m or more in maximum near shore and generally thinned out to be few centimeters in the inlands. Separate from these deposits, many boulders were scattered on the lowlands, and they have deposited until 750 m from the shoreline. Interestingly, thicknesses and grain sizes of the layered tsunami deposits also showed rapid declination at the same point where many of the boulders have deposited. The 2011 Tohoku-oki tsunami deposits were also studied in Ibaraki and Chiba prefectures, but the inundated area and tsunami height were appreciably small comparing to those in Miyako City. They were composed of mud to fi ne sand, and rarely included medium and coarse sand. The faces of tsunami deposits varied depending on component materials of source area. Because of the geomorphic change or limited range of the grain size that constitute in source area, the inland grain-size fi ning trends were verifi ed in limited areas, while the thinning trend towards the inland distribution limit was confi rmed at all of the study sites regardless of their grain size.

108 7&8-34

The 2011 M6.4 Shizuoka earthquake sequence: triggering process investigation

Anca Opris1, Bogdan Enescu2, Yuji Yagi2, Sachiko Tanaka3, and Katsuhiko Shiomi3

1Graduate School of Life and Environmental Sciences, University of Tsukuba 2Faculty of Life and Environmental Sciences, University of Tsukuba 3National Research Institute for Earth Science and Disaster Prevention

Many inland areas in Japan were seismically activated following the 2011 M9.0 Tohoku-oki earthquake. The activation mechanism includes triggering by dynamic, static or fl uid-induced stress changes (e.g., Toda et al., 2011; Miyazawa et al., 2011; Shimojo et al., 2014). In this study we aim to understand the triggering processes associated with the 2011 M6.4 Shizuoka earthquake sequence; the mainshock of the sequence occurred on March 15, close to Mt. Fuji. Enescu et al (2012) argued that the delay of activation in the Shizuoka area supports the static stress triggering mechanism rather than the dynamic one, but time-dependent adjustment of local pore pressure changes could also be involved. To improve the detection of smaller earthquakes, we applied the Matched Filter Technique (MFT) (Peng and Zhao, 2009) for the time interval from the Tohoku-oki earthquake until seven hours from the Shizuoka event. We used Hi-net (NIED) continuous and template waveform data. No foreshock activity was detected prior to the March 15 Shizuoka earthquake, which contrasts with other similar inland seismicity activations (e.g., Kato et al., 2013; Shimojo et al., 2014). The aftershock detection for the seven hours following the M6.4 event was signifi cantly improved. When looking at the space-time distribution of the MFT detections, we observe that the earliest aftershocks (fi rst minutes after the Shizuoka main shock) occurred to the south of the mainshock, close to Mt. Fuji. We speculate that such early activation might be related to fl uid-related processes, however more analysis is necessary to interpret these results. Considering the aftershock decay, a relatively high p-value is observed. According to Dietrich’s rate-and-state model (Dieterich, 1994), it could be related to a non-constant stressing rate following a large earthquake. If the stress decreases by the logarithm of time, rapid decay of aftershocks are expected.

109 7&8-35

High-frequency rupture along the complex fault system during the 2008 Mw 7.9 Wenchuan, China, earthquake

Ryo Okuwaki1 and Yuji Yagi2

1Graduate School of Life and Environmental Sciences, University of Tsukuba 2Faculty of Life and Environmental Sciences, University of Tsukuba

Earthquakes often occur along a complex-fault system consists of bending, step-overs, or multiple-fault planes (e.g., King & Nabelek, 1985). Such complexity can bring about heterogeneous stress/strength distribution and consequently an irregularity of rupture propagation (e.g., Aki, 1979; Duan & Oglesby, 2005). Generation of high-frequency (HF: ~1 Hz) seismic waves is sensitive to the irregularity of rupture propagation (e.g., Spudich & Frazer, 1984). Thus tracking HF-radiation sources at high resolution is a key to understand earthquake source physics especially for an earthquake with a complex-fault system. The 2008 Wenchuan, China, earthquake occurred along such a complex-fault system (e.g., Xu et al., 2009). Seismic source models from low-frequency-seismic data have revealed the following features: unilateral rupture propagation, two or three major sub-events (large slips), and changes in slip- motion from pure thrust to strike-slip during rupture propagation (e.g., Shen et al., 2009; Yagi et al., 2012). Images of HF (~1 Hz) rupture from back projection analyses (e.g., Xu et al., 2009) also show that there are two or three sub-events of HF bursts along the fault traces. However because of a poor resolution of back projection in both lateral and dip-extents, a detailed role of HF radiation related to the fault geometry or changes in slip-motion has been poorly addressed. In this study, we analyze teleseismic HF (0.5–2.0 Hz) waves by using a hybrid back projection (HBP: Yagi et al., 2012) method. Because the HBP method extracts signals of HF radiation by cross-correlating observed waveforms and Green’s functions including the direct P-wave and the depth phases (pP and sP), the resolution in depth can be given to the HBP images, and the effects of changes in slip-motion on HF radiation can be considered. At the TGSW session, we present a role of HF radiation, related to the complex-fault system and variation in slip-motion during rupture.

110 7&8-36

Complex rupture process of the 2013 Sea of Okhotsk deep earthquake at depth of spinel stable area

Suguru Endo1, Atsushi Nakao2, Shiro Hirano3, and Yuji Yagi4

1Geosciences, Graduate School of Life and Environmental Sciences, University of Tsukuba 2Graduate School of Science and Engineering, Tokyo Institute of Technology 3Department of Physical Sciences, College of Science and Engineering, Ritsumeikan University 4Faculty of Life and Environmental Sciences, University of Tsukuba

The 2013 Sea of Okhotsk deep earthquake (Mw 8.3; depth 608.9 km), which is the largest deep earthquake ever recorded, occurred within the subducting Kurile-Kamchatka slab. Some studies have investigated the Okhotsk deep earthquake (Zhan et al., 2014; Meng et al., 2014) and compared this event’s rupture process with that of the 1994 Bolivia deep earthquake (Mw 8.3; depth 635.4 km). They argued that transformational faulting in Metastable Olivine Wedge (MOW) is associated with the source process of the Okhotsk deep earthquake. Moreover, they suggested a complex rupture process involving the backward propagation from low-frequency analysis. For the purpose of confi rming the complex rupture process of the Okhotsk deep earthquake, we applied the Hybrid Back–projection (HBP) method (Yagi et al., 2012) and the waveform inversion method. To verify the transformational faulting model, we estimated the relationship between the thermal structure of the slab and the deep seismicity in the Kurile-Kamchatka region, and evaluated the persistence of the MOW at hypocentral depth. We found the backward propagation at the SSE region from the hypocenter and the re- rupture in the hypocentral region in the high-frequency analysis. The results of the calculation of the slab temperature and the depth distribution of seismicity indicated that the dense seismicity (depth 370–550 km) can be associated with transformational faulting. However, at the depth of 550–660 km (involving the hypocenter depth), the transformational faulting is not valid for the occurrence of the Okhotsk event (also other seismic events at this depth range) because there are few seismic events and the metastable olivine has already transformed to the spinel in terms of the slab temperature, i.e., there is no longer the MOW. Therefore, the spinel rather than the metastable olivine contributed to the rupture process of the Sea of Okhotsk deep earthquake.

111 7&8-37

The relationships between slow-slip events and seismicity in the Hyuga-nada region, SW Japan

Yuta Yamagami1, Bogdan Enescu2, and Yuji Yagi2

1University of Tsukuba, Graduate School of Life and Environmental Sciences 2University of Tsukuba, Faculty of Life and Environmental Sciences

In the subduction zone of southwest Japan, slow-slip events (SSE), which are characterized by longer duration than regular earthquakes, have been reported (e.g., Obara, 2002). Some studies have proposed the correlation between SSEs and megathrust earthquakes: an SSE likely preceded the 2011 Tohoku-oki earthquake (e.g., Kato et al., 2011); numerical simulations suggest that SSEs effect the seismic cycle (e.g., Matsuzawa et al., 2010). Therefore, the monitoring of SSEs might prove a key-element to disaster prevention. However, due to limitations in the coverage and sensitivity of geodetic networks, smaller SSEs may go undetected. Researchers suggested that seismicity might be a good proxy to detect SSEs (e.g., Llenos et al., 2009; Okutani and Ide, 2011; Marsan and Enescu, 2012), since they often trigger earthquake swarms. We focus on the Hyuga-nada region, located in the southwestern part of the Nankai Trough. This region is one of the most seismically active in Japan, large earthquakes (M7- class) occurring every 10-20 years. However, M8-class earthquakes, which occur in other parts of the Nankai Trough, have not been observed; such a feature is consistent with its moderate interplate coupling (Wallace et al., 2009). In this presentation, we fi rst make an overview of the seismicity in the area. We then estimate the completeness magnitude, using the procedure of Wiemer and Wyss (2000). The b-value of the Gutenberg-Richter law is 0.7, lower than the average value (~1.0) reported for the world-wide seismicity. Nevertheless, it is consistent with the relatively low b-values found in subduction zones (e.g., Tormann et al., 2015). As a result of removing the aftershock sequences by using the declustering approach of Marsan and Lengline (2008), we could identify some earthquake swarm sequences. We will analyze next in more detail the possible association of these swarms with the SSEs detected by analyzing geodetic data (Nishimura, 2015).

112 9 Green and Life Innovations by Algae Biomass

Tuesday, September 29 Venue: Conference Room 303

Green and Life Innovations by Algae Biomass

The use of algae biomass as an alternative of fossil fuel for the production of fuel, chemicals, food, health supplments, cosmetics, etc., has attracted worldwide attention in recent years. A number of algal venture businesses have been growing in the world. Algae technology is not yet mature in the world, but because of such incredible potential, algae might grow to be a new big market in the future. In this session, we will learn some R&D topics of algae biomass and discuss with distingushed speakers about the technical and/or social bottlenecks and how to solve them.

Session Organizer: Makoto M. Watanabe

Opening address by the session organizer Makoto M. Watanabe ABES, University of Tsukuba 9:00 - 9:20 Algae Biomass and Energy System R&D Center (ABES), Unversity of Tsukuba: The benefi ts of algae to all humankind Part One Algae biomass for the future Chair: Kazuo Kadowaki Qiang Hu Institute of Hydrobiology, CAS, China 9:20-9:50 Toward sustainable production of microalgal biomass: Key problem identifi cation and possible solutions Stephen Mayfi eld 9:50-10:20 Photosynthetic bio-manufacturing in green algae: Food and fuel for the 21st Century 10:20-10:40 Discussion, Summary and Break Part Two Algae biomass and fuel productions Chair: Iwane Suzuki Rupert Craggs NIWA, New Zealand 10:40-11:10 Hectare-scale wastewater treatment and resource recovery high rate algal ponds of algae biomass Mitsutoshi Nakajima University of Tsukuba 11:10-11:40 Downstream processing: Separation and concentration of microalgae for fuel production 11:40-12:00 Discussion and Summary Part Three Bioactive compounds from algae Chair: Makoto M. Watanabe Hywel Griffi ths Fermentalg, France 13:00-13:30 Mixotrophic fermentation: The best of both worlds Masaki Yoshida University of Tsukuba 13:30-14:00 Triterpenic hydrocaron “squalene” from Aurantiochytrium Hiroko Isoda University of Tsukuba 14:00-14:30 Medicinal functions of Aurantiochytrium and squalene 14:30-15:00 Discussion, Summary and Break

113 Part Four Bioplastics and cosmetics from algae Chair: Masashi Kijima Masatoshi Iji NEC 15:00-15:30 Current industry and technologies of bioplastics and coming application of algae biomass Kinya Atsumi DENSO 15:30-16:00 DENSO Algae Green Project: Algae fuel and “moina” hand cream 16:20-17:00 Discussion, Summary and Performance

114 9-1

Algae Biomass and Energy System R&D Center (ABES), University of Tsukuba: The benefi ts of algae for all humankind

Makoto M. Watanabe

Algae Biomass and Energy System R&D Center, University of Tsukuba

The University of Tsukuba (UT) established the Algae Biomass and Energy System R&D Center (ABES) with a focus on research and industrialization capacity on July 1, 2015. ABES has a robust interdisciplinary structure that meets the requirements for developing and commercialising algae fuels and products in combination with other natural energy systems. UT identifi ed the strengths and capacity of algae and energy researchers in biology, chemistry, engineering, and medicine within the university which clearly has signifi cant relevant skills and infrastructure. The integration of these skills into ABES could provide a very strong and enhanced research capacity. Development of the research and industrialisation capacity needs to be further expanded through additional collaboration between UT and other relevant research groups at other Japanese and overseas universities, research organizations, and also with the industry. ABES has close links with the industry and relevant National Research and Development Agencies with the aim of establishing algae-energy industry bases in Japan. The successful commercialisation of university research has often involved university researchers setting up companies based on their university research, or assisting and leading these companies in commercialisation activities. ABES offers the Life Innovation Programme to cultivate the researchers who can achieve the transition from academia to industry. ABES will set further and regular strategic planning and priority in all areas including research and development activities, human resource requirements, management structures and processes, and pathways to commercialisation for extending benefi ts of algae to all humankind and creating the best-mix natural energy system.

115 9-3

Photosynthetic bio-manufacturing in green algae: Food and fuel for the 21st Century

Stephen Mayfi eld

Department of Molecular Biology, University of California San Diego, and The California Center for Algae Biotechnology

Fuel, food, and all biological products are simply different forms of chemical energy, and as such are closely related. All of these products are ultimately derived from photosynthesis, the process by which sunlight energy is converted to chemical energy. Over the last 100 years we have exploited cheap fossil fuels to drive unprecedented economic and agricultural growth, but in so doing we have released sequestered CO2 into the atmosphere, which is now beginning to impact our climate. In addition, fossil fuel reserves are fi nite, and we are now starting to see the initial signs of depletion of these reserves, including the rising cost of fuel and food. Eukaryotic algae offer tremendous potential for the large scale production of biofuels and bio-products as algae require only sunlight as an energy source and sequester CO2 during the production of biomass, and algae can be much more effi cient then terrestrial plants in fi xing

CO2 and producing biomass. Using “designed for purpose” photosynthetic organisms we have the opportunity to develop production platforms for fuel, food, and biomaterials that have unmatched effi ciencies and productivities. We are developing the genetic and synthetic biology tools to enable the production of designer algae as bio-products platform. The challenges, potential, and some early successes of synthetic biology in algae for the production of high value products will be discussed.

116 9-4

Hectare-scale wastewater treatment and resource recovery high rate algal ponds

Rupert Craggs, Jason Park, Donna Sutherland and Stephan Heubeck

National Institute of Water and Atmospheric Research Ltd (NIWA), PO Box 11115, Hamilton, 3251, New Zealand

High Rate Algal Pond (HRAP) systems are an effective and economic upgrade option for conventional wastewater treatment ponds, providing improved natural disinfection and nutrient removal. Moreover, wastewater nutrients are recovered as harvested algal biomass for benefi cial use as fertilizer, feed or biofuel feedstock. Low-cost construction and operation are crucial factors for the adoption of HRAP. Economic design, construction and operation methods for unlined, earthen hectare-scale demonstration HRAPs treating domestic wastewater at Christchurch and Cambridge wastewater treatment plants will be compared in context of earlier pilot and full-scale systems. The Christchurch system consisted of four 1.25-hectare HRAPs that were fed with settled primary sewage and the algae were harvested in above ground lamella settler tanks. The Cambridge system consisted of two 1-hectare HRAPs that were fed with Anaerobic Pond effl uent and the algae were harvested using in-ground Algal Harvest Ponds to settle and concentrate the algal biomass. The Cambridge HRAP and algal harvest ponds were part of a complete Enhanced Pond System including the Anaerobic Pond which was covered to capture biogas energy from the wastewater solids and a Covered Digester Pond to recover biogas energy from the harvested algal biomass, as well as nutrients as a concentrated digestate. Further effl uent polishing was provided by Maturation Ponds to achieve higher quality effl uent. All of the ponds were of earthen construction and were made within existing or disused conventional wastewater treatment ponds. Cost-effective earthen pond construction combined with the use of protective geotextile and geomembrane liners, geomembrane covers, painted steel paddlewheels, and precast concrete carbonation sumps enable economic implementation of EPS for energy effi cient and effective wastewater treatment as well as nutrient recovery and energy production for small to medium-sized communities.

117 9-5

Downstream processing: Separation and concentration of microalgae for fuel production

Mitsutoshi Nakajima, Sosaku Ichikawa, Ryozo Noguchi, Junko Ito, Mikihide Demura, and Makoto Watanabe

Algae Biomass and Energy System R&D Center, Faculty of Life and Environmental Sciences, University of Tsukuba

The algal biomass project is now being implemented as one of the potential recovery measures for Fukushima. There are several methods to produce fuel from microalgae, such as hydrothermal liquefaction (HTL) or bio-gasifi cation. In any process, the microalgae culture needs to be highly concentrated because of their natural low concentration. Therefore, there is a great need for the development of a low-cost and highly-effi cient process of concentration. We have been attempting to concentrate by gravitational settling, coagulation using coagulants, vacuum fi ltration and centrifugal fi ltration using a washing machine. First, gravitational settling and coagulation were attempted, and cationic coagulants were used. In gravitational settling, it took about 10 hours, and the concentration of solid content of the precipitate was 30 times higher than that of the algal culture. With aggregation, the process took a few minutes, however only a 5 times higher-concentration was obtained in the aggregates by using a polymer coagulant. Larger aggregates were formed by a high-cationic coagulant. The sedimentation rates were almost constant when the concentration of coagulant was higher than 8 mg/L. Below 8 mg/L, the sedimentation rate decreased drastically. In case of gravitational settling, the process takes a long time but the supernatant can be recycled. It is necessary to test whether the supernatant from aggregation process is reusable or not. Centrifugal fi ltration using a washing machine was also done. Several fi lters were tested by vacuum fi ltration, and the one which has high fi ltration rate and high solid content rejection was selected. The selected fi lter was fi xed to the washing machine, and centrifugal fi ltration was carried out. As a result, the culture was concentrated 86 times to reach about 4.0 % solid content, and 80 % of solids were recovered. The consumed power was higher than the other processes, suggesting the need to further consider the effi ciency of throughput. Currently, using sedimentation tanks with about 70 L and 200 L in volume and 1 m height, repeated batch sedimentation and fi ltration/pressing were carried out to get suitable amount of precipitates, for hydrothermal liquefaction (HTL) samples. In HTL batch experiments, relatively lower pressures were applied to production of fuel, compared conventional super-critical and sub-critical conditions.

118 9-6

Mixotrophic fermentation: The best of both worlds

Hywel Grif fi ths

Fermentalg, Libourne, France

Most, if not all, algae respond to light in various manners and even relatively small changes in the amounts of light they receive can have quite profound effects on the metabolism of the cells. In contrast, for many algae, the best productivity, consistency and control are experienced in heterotrophic culture in the dark. The French company Fermentalg has developed and patented novel technology that allows it to introduce light into industrial-scale closed fermentation processes to give mixotrophy at grand scale. Even in high-density cultures where the distance light can travel is limited, light can be used to alter how cells respond to other stimuli, the substrates they use, and the products they produce. In this mixotrophic mode, the wavelength, duration and periodicity of the exposure to light must be carefully chosen for each process, to ensure suffi cient effect but also to avoid unnecessary energy expenditure, which can have an economic impact at industrial scale. By using this technology, Fermentalg is opening up many strains of algae to industrial exploitation under tightly controlled fermentation conditions with all the associated advantages of scale and control that this brings.

119 9-7

Triterpenic hydrocarbon “squalene” from Aurantiochytrium

Masaki Yoshida

Faculty of Life and Environmental Sciences, University of Tsukuba

The production of biomass from heterotrophic algae is currently attracting great attention because of its advantages; high growth rate, no requirement of light, space-saving culture vessel, quality controlled production process, and so on. Many heterotrophic algae are subjects of research and development and several organisms are in commercial stage. Aurantiochytrium, formerly a part of Schizochytrium, is a genus belonging to the Labyrinthulomycetes. Aurantiochytrium is a colorless, fungus-like algae. This group of algae has been known to produce PUFAs and occupies an important position in the marine ecosystem. A novel strain of Aurantiochytrium that accumulates high amounts of squalene was reported in 2010 and the way to biofuel production had been paved. Squalene is a polyunsaturated triterpene hydrocarbon and it can be used as not only alternative of petrodiesel but also foods, cosmetics, and medical products. Squalene accumulation and oil drop formation in Aurantiochytrium cells is transient during culturing process. Ability of the accumulation of squalene highly correlated with both the strain locality and phylogeny of the genus Aurantiochytrium. Because of heterotrophy, the supply of carbon and nitrogen source is an important issue in terms of the cost of Aurantiochytrium culture. The exploitation of wastewater or other residual organic dross from industries is a promising approach for inexpensive cultivation of Aurantiochytrium and other heterotrophic organisms.

120 9-8

Medicinal functions of Aurantiochytrium and squalene

Hiroko Isoda1,2

1Faculty of Life and Environment, University of Tsukuba 2Alliance for Research on North Africa (ARENA), University of Tsukuba

Algae are known to exhibit various biological and physiological activities including antioxidant, anticoagulant, antiviral, and antitumor activities. Indeed, several species of green algae, brown algae and red algae have been found to contain polysaccharides and glycoproteins w i t h b i o a c t i v i t i e s . T h e r e h a v e b e e n , h o w e v e r, n o r e p o r t s e x p l o r i n g t h e e f f e c t s o f Aurantiochytrium and squalene on anti-stress and anti-infl ammatory effects. The fi rst part of this study included the study of anti-stress properties of Aurantiochytrium and squalene extracts using in vitro and in vivo models. Stress affects damage in all categories of cells, particularly neuronal cells inducing neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease. We expected the protective effect of these algae extracts against neuronal damage improving neuronal differentiation in PC12 cells, when treated with NGF or NGF-like compounds, PC12 cells cease proliferation and take a number of differentiated phenotypic properties of sympathetic neurons, including neuritis outgrowth and increase in AChE activity. On the other hand, they act against depression and anxiety when the mice were exposed to tail suspension test. In the following step, we investigate the anti-infl ammatory effects of Aurantiochytrium and squalene extracts on RAW264.7 cells and explore the molecular mechanisms associated with the anti-infl ammatory effects of algae extracts. Chronic infl ammation is an underlying cause of several pathological disorders including insulin resistance, dementia, atherosclerosis, and cancer. Non-steroidal anti-infl ammatory drugs (NSAID) are generally used to treat acute and chronic infl ammatory conditions. However, due to their adverse side-effects and increased cardiovascular disease risks associated with chronic use of several NSAID, there is a critical need to identify natural products with anti-infl ammatory properties. In this study, we investigated the inhibitory effect of Aurantiochytrium and squalene extracts on the secretion of pro-infl ammatory cytokines (IL-1b, IL-6 and TNF-a), and NO production by RAW264.7 cells in the presence or absence of algae extract. In summary, we have found evidence that the Aurantiochytrium and squalene extracts may be benefi cial in the stress treatment and the prevention of infectious infl ammation diseases.

121 9-9

Current industry and technologies of bioplastics and coming application of algae biomass

Masatoshi Iji1,2 and Makoto Watanabe3

1Smart Energy Research Laboratories, NEC Corporation 2Cooperative Graduate School, Division of Materials Science, University of Tsukuba 3Algae Biomass and Energy System R&D Center, University of Tsukuba

As an alternative to petroleum-based plastics, biomass-based plastics (bioplastics) have distinct advantages, such as the ability to fi x the CO2 gas that causes global warming and prevent exhausting petroleum resource. Biomass-based polyester such as polylactic acid (PLA) and polyethylene terephthalate (bio-PET), polyethylene(bio-PE), and polyhydroxylbutyrate (PHB) are representative bioplastics, which are being mass-produced (the total amount is more than one million tons/year). We have developed highly functional bioplastics to be used in durable products including electronic products. While fully preserving the high plant ingredient ratio and safety, we have improved PLA’s practicability, and have also endowed it with desirable new properties. The fl ame retardant PLA composite with a metal hydroxide is used in various electronic product parts (Y. Kiuchi, M. Iji et al., Poly. Deg. Stab., 109: 336-342, 2014). Furthermore, we have studied new functional PLA composites that offer new performance attributes: shape memory and high heat-diffusion of PLA (A. Nakamura, M. Iji, J. Mater. Sci., 44: 4572-4576, 2009). On the other hand, the currently mass-produced bioplastics use starch as the main resource, which is produced from plants that are generally edible. Fears of future food shortages, however, are driving an effort to use plant resources that are not edible. Therefore, we have developed a new cellulose-based bioplastic using stable non-food plant resources. It was produced by bonding cellulose, the main component of most plants, and cardanol, a unique structured phenol derivative with a long side chain, derived from cashew nut shell generated as a byproduct (M. Iji, K. Toyama et al., Cellulose, 20(1): 559-569,2013). Algae biomass is greatly expected as a non-food resource for bioplastics because of its stable supply in future and its various chemical structures that can create high functions for bioplastics. In the algae biomass, long chain fatty acids, hydrocarbons and polysaccharide will be valuable components of the cellulose-based bioplastic.

122 9-10

DENSO Algae Green Project: Algae fuel and “moina” hand cream

Kinya Atsumi and Hiroki Kuriyama

New Business Promotion Dept., DENSO CORPORATION

DENSO has been involved in algal research since 2008. The purpose of the projects was to study whether the lipid of microalgae would be applicable as biofuel for automobiles or not. We have been investigating cultivation systems and focusing on two specifi c microalgae such as Botryococcus braunii and Pseudochoricystis ellipsoidea. Toyota Central R&D Labs., Inc. and DENSO are quite interested in the oil of the non-oxygenated hydrocarbons which B.braunii produces. University of Tsukuba and we undertake studies jointly on the algae- based biofuels and evaluate the combustion using visualization in a specifi cally developed chamber. We also look at the value added applications utilizing algal pure oil and fi nally we have developed and commercialized it in November, 2014, as an aromatic moisture cream. On the other hand, although the oils which P.ellipsoidea produces are common triacylglycerols (TAGs), it is easy to cultivate outdoor because of the acidic medium culture. The extracted oils are converted into hydro-treated-biodiesel (HBD) as drop-in fuel. DENSO also constructed larger scale raceway ponds at our Zenmyo factory, and started operation on July, 2010. This facility for development is standing on the materials-recycling concept. In order to accomplish energy-saving system of cultivation, the waste-materials and energy such as the CO2 in the exhaust fl ue gas and the exhaust heat of vapor from a cogeneration power system have been utilized. Further, the effl uent of activated sludge plant in the factory is reused as cultivation water. To improve the oil productivity, genetic recombination techniques and mutagenesis methods have been carried out with Chuo University under NEDO and MAFF projects. The main achievement in the R&D mentioned above will be presented.

123 NOTE

124 10 International Collaboration for Grassland Conservation in North-East Asia

Monday, September 28 Venue: Conference Room 403 International Collaboration for Grassland Conservation in North-East Asia

Excessive grazing due to large numbers of livestock causes severe degradation of natural grassland. Furthermore, the vegetation cover of grassland has been reduced by extensive droughts caused by recent climatic changes in continental East Asia. These changes are likely to result in severe soil degradation and the release of large quantities of soil dust into the atmosphere. In this session, we introduce the international collaboration for grassland conservation in Northeast Asia.

Session Organizers: Kenji Tamura and Kiyokazu Kawada

Chair: Kenji Tamura, University of Tsukuba Bandi Namkhai Hustai National Park, Mongolia 10:20-11:00 Hustai National Park management Undarumaa Jamsran Mongolian University of Life Sciences 11:00-11:45 Conservation of rangeland ecosystems in Mongolia 11:45-12:30 Discussion

125 10-1

Hustai National Park management

Bandi Namkhai

Hustai National Park, Mongolia

There are 99 protected areas in Mongolia and they are categorized in four different levels: (1) Strictly Protected Area, (2) National Park, (3) Natural Reserve, and (4) Historic Site. Hustai nuruu area is located at the conjunction where forest, mountain range and steppe terrains meet, and was chosen as a protected area in 1993. The government is in charge of protected areas administration, but Hustai National Park (HNP) management was carried out by an NGO from the beginning under an agreement with the government. Hustai National Park Trust (Hustai Trust) is the management NGO that successfully self-sustains the operation without receiving any support from the government budget. Hustai Trust became an IUCN member in 2002, and HNP was registered in UNESCO’s Man and Biosphere network in 2007. These events helped the Park’s publicity internationally. The following are Hustai Trust’s fi ve main activities: (1) Conservation of HNP ecosystem and historic sites, (2) Reintroduction of the wild horse, the only one remaining in the world, (3) Organize international researches and trainings, (4) Development of eco-tourism, and (5) Assist local communities to improve their sustainable livelihood. The performance indicators of Hustai Trust’s main activities are: (1) As a result of successful environmental protection, heads of wild life in the Park are increasing continuously. Also some other species of wildlife such as Argali (big horn) sheep and antelopes are migrating themselves to the Park, and their number is increasing; (2) 84 takhis (wild horses) were brought from Holland in 1992-2000. Now we have the largest population in the world. They roam freely throughout the year in the Park; (3) During the past 18 years, 52 students from more than ten foreign countries, and 262 students from domestic universities have conducted researches in HNP. We have concluded cooperation agreements with fi ve universities in Japan as well as universities and research institutions in Holland, US, Germany and UK, and organized joint trainings and researches. Hustai Trust also regularly organizes national and international scientifi c conferences and seminars; (4) Hustai Trust’s main source of revenue is tourism. We receive about 11000 foreign and 7000 domestic visitors a year. Main attraction for our visitors are pristine nat ure, wild life, historic sites, birds and also visits to nomadic families to experience their lifestyle and culture; and (5) Affective protection of the Park’s ecosystem is not possible without involvement of the local community. In order to achieve close cooperation with the local community, the following activities are carried out, such as: herders are organized in groups; establishment of Buffer-zone Council to govern the cooperation between the municipal government, local community, and Hustai Center; and the Buffer Zone Development Fund was established. During the past 18 years, this fund has issued soft loans to 711 people of the local community with total sum of USD 1 million. Factors to Hustai Center’s achievement are the following: (1) Series of international projects were carried out with grant aid funded by the Dutch Government; (2) Transparent self-governance that is not dependent on the government; and (3) Hustai Trust’s management structure and regulations enable effi cient operation.

126 10-2

Conservation of rangeland ecosystems in Mongolia

Undarmaa Jamsran1, Manibazar Norov1, Oyunsuvd Sumiya1, Diimaa Sangi1, Narangerel Theden-ish1, and Toshiya Okuro2

1Center for Ecosystem Studies, Mongolian University of Life Sciences 2Graduate School of Agricultural and Life Sciences, The University of Tokyo

Mongolia has a great variety of ecosystems, such as high mountains, mountain forests, mountain forest steppe, steppe and desert steppe and desert, and rangelands which comprise over 80% of the total area of Mongolia. Rangelands in Mongolia serve as a source not only of forage, but also of various ecosystem services such as high quality of water, clean air and economic means of agriculture, mining, etc. The ever-growing demands for ecosystem services are compounded by increasingly serious degradation of ecosystems to supply services. The increasing gaps between ecosystem service supply and demand diminish the prospects for sustainable development in Mongolia. Consequently, goals of conservation of the rangeland ecosystems are conceived in reducing system variability, maintaining ecosystem resilience, avoiding thresholds, and improving predictability. In the present study, we have tested restoration capability of the rangeland vegetation, using well-studied plant communities that exist along grazing gradients. To accomplish this, we established exclosures along grazing gradient in two types of rangelands in steppe and desert steppe zones of Mongolia. Each exclosure was established in 2004, and we have examined fl oristic composition, and soil seed bank outside and inside of each exclosure at each site between 2005 to 2014. The fl oristic compositions in the permanent plots outside and inside each exclosure were similar from 2005 to 2014, indicating that some variations in fl oristic compositions were mainly associated with annual rainfall. Floristic composition of soil seed bank showed that all plots in pre- and post- threshold states contain mostly seeds of annual weed species. Thus, our results suggest that the tested rangeland vegetations in steppe and desert steppe ecosystems may not recover by soil seed bank.

127 NOTE

128 11 Plant Science for Food Security and Sustainable Agriculture

Monday, September 28 Venue: Conference Room 303

Plant Science for Food Security and Sustainable Agriculture

As the world population has increased exponentially, there is an increasing demand for crop production all over the world. However, global warming has recently triggered abnormal climate conditions, such as severe dryness or fl ooding, in higher frequency than before. In addition, incidence of lethal pathogens is expected to threaten stable agricultural production in near future. To establish sustainable agriculture and food security globally, it is now required to develop effi cient breeding methodology that enables construction of elite cultivars within a short time. For this purpose, inter- disciplinary approach, which combines physiology, omics, and genomics, is essential. It is also important to understand the diversity of crop physiology, because each crop has characteristics that are never seen in the model plant. In this session, we will have lectures by six outstanding plant scientists. Their topics will include fruit biology, systems biology, metabolomics, proteomics, and new breeding technologies. Through the lectures, we will discuss how knowledge of plant science can be applied to effi cient crop breeding.

Session Organizers: Ryoichi Yano, Tohru Ariizumi, Yasuhiro Ishiga, Yoshihiro Okabe, and Natsuko Kinoshita

Part One Chair: Tohru Ariizumi, University of Tsukuba Yves Gibon French National Institute for Agricultural Research (INRA) 9:05-9:40 Fruit systems biology Miyako Kusano University of Tsukuba 9:40-10:10 Tomato metabolomics and food security Chun-Ta Wu National Taiwan University Non-climacteric ripening characteristics of ‘Jen-Ju Bar’ guava (Psidium 10:10-10:40 guajava L.) is a result of the defect in expression of system II ACC synthase PgACS1 Part Two Chair: Yasuhiro Ishiga, University of Tsukuba Hirofumi Nakagami RIKEN, Center for Sustainable Resource Science 11:00-11:30 Towards durable and broad-spectrum resistance: Post-genomic strategies to understand conserved immune system in land plants Akito Kaga National Institute for Agrobiological Sciences (NIAS) 11:30-12:00 Toward construction of a high-density mutant library in soybean Masaki Endo National Institute for Agrobiological Sciences (NIAS) 12:00-12:30 The use of site-specifi c nucleases for plant molecular breeding

129 11-1

Fruit systems biology

Sophie Colombié1, Bertrand Beauvoit1, Christine Nazaret2, Benoit Biais1, Camille Bénard1,3, Marie-Hélène Andrieu1, Stéphane Bernillon1,3, Mickaël Maucourt1,3, Duyên Prodhomme1,3, Cécile Cabasson1,3, Catherine Deborde1,3, Daniel Jacob1,3, Patricia Ballias1,3, Annick Moing1,3, Dominique Rolin1,3, Jean-Pierre Mazat4, Martine Dieuaide-Noubhani1, and Yves Gibon1,3

1INRA & Bordeaux University, Fruit Biology and Pathology Unit 2Institut de Mathématiques de Bordeaux, ENSTBB-IPB 3Bordeaux Metabolome Platform 4Bordeaux University

A key goal of fruit biology is to understand the factors that infl uence fruit growth and quality, ultimately with a view to manipulating these levels for improvement of fruit traits. Metabolism is an obvious target for crop improvement, especially in fruits, and understand- ing the mechanisms linking it to phenotypes will help to focus breeding strategies. However, metabolism is extremely complex, with a number of highly intricate pathways that undergo a profound reprogramming throughout fruit development and maturation, making it very dif- fi cult to fi nd the right targets for improvement. Systems biology, which can be defi ned as an approach iterating theorisation and experimentation, represents a great opportunity to cope with such complexity. We have developed and validated two models describing tomato fruit metabolism: a compartmented enzyme-based kinetic model consisting in sets of ordinary dif- ferential equations for each step in sucrose metabolism and a stoichiometric model describing large sectors of primary metabolism. To parameterise and validate these models, we have performed a series of phenotyping experiments, in which we collected a range of climatic and eco-physiological data as well as a large set of samples that have been analysed for enzyme ac- tivities, metabolome and structural traits. The models then enabled a series of fi ndings, which include a better understanding of the osmotic-driven vacuole expansion during cell division and the occurrence of an excess in energy just before the onset of ripening as supporting the concept of the climacteric crisis.

130 11-2

Tomato metabolomics for food security

Miyako Kusano

Faculty of Life and Environmental Sciences, University of Tsukuba

Metabolomics is widely applied to investigate metabolic impacts by mutation(s) in a genome or environmental changes occurred in plants. Because metabolites are produced through transcriptional and translational events, and thus can be regarded as the closest phenotype correlated to visual phenotype(s). Here we introduce recent activities for the use of metabolomic approaches to elucidate metabolic impact from transgene induction to tomatoes as an example of food security studies. We conducted objective validation of metabolite composition in two genetically-modifi ed tomatoes (GMT), overexpressing melon 3-hydroxy-3-methylglutaryl- coenzyme A reductase (HMGR) and miraculin to the same genetic background cultivar (cv. Moneymaker, MM). The former GMT showed larger fruit size than miraculin-overexpressing fruits, while there were no differences of visual phenotypes between milaculin-overexpressing and MM fruits. Comprehensive metabolite profi ling revealed that slight but clear difference was observed between the groups of HMGR-overexpressing lines and the groups of miraculin- overexpressing and MM fruits. The objective validation by comparing three known cultivars and the two GMTs demonstrated that the two GMTs showed over 80% of the similarities when compared to MM in terms of metabolic composition.

131 11- 3

Non-climacteric ripening characteristics of ‘Jen-Ju Bar’ guava (Psidium guajava L.) is a result of the defect in expression of sys- tem II ACC synthase PgACS1

Chun-Ta Wu

Department of Horticulture and Landscape Architecture, National Taiwan University

‘Jen-Ju Bar’ (‘JJB’) guava (Psidium guajava L.) exhibited a long postharvest life is attributed to its non-climacteric characteristics, including delayed peel coloration and pulp softening, resulting from reduction in activity of 1-aminocyclopropane-1-carboxylic acid (ACC) synthase (ACS), the key enzyme in ethylene biosynthetic pathway, and, thus, the usually massive amount of ethylene produced during ripening. To elucidate the underlying physiologi- cal mechanism, two cDNA clones of ACS, PgACS1 and 2 were isolated from guava pericarp and characterized for their expression patterns in the fruit. A signifi cant mRNA accumulation of PgACS1 in ‘Li-Tzy Bar’ (‘LTB’) fruit, a climacteric guava cultivar, was found after mature- green stage; whereas PgACS1 transcript was undetectable over the fruit development of ‘JJB’. In contrast, PgACS2 displayed a low and steady expression in pulp tissues of both cultivars. Furthermore, PgACS1 was upregulated by ethylene and suppressed by 1-methylcyclopropene, an ethylene action inhibitor. PgACS1, therefore, was considered as a system II ACS of guava. A profi le of Southern blotting clearly demonstrated that PgACS1 does exist in the genome of ‘JJB’, which implied a defect in PgACS1 expression in the ripening phase of this cultivar. The PgACS1 promoter regions (about upstream 2 kbp) of ‘LTB’ and ‘JJB’ obtained by using Genomic Walking technique were compared and found that only 46% identity between these two sequences. There were two Ethylene Response Elements (ERE) located in the former; but no ERE was detected in the latter. Blasting analysis showed hit sequence retrotransposon V12 had 67% sequence identity to ‘JJB’ PgACS1 promoter, which suggested sequence differences of PgACS1 promoter region between ‘LTB’ and ‘JJB’ were very likely caused by insertion of a retrotransposon leading to a massive shift of cis-elements and gene inactivation. Because not enough ACC is produced by PgACS1 to support autocatalytic ethylene synthesis at ripening, ‘JJB’ fruit behaved in a non-climacteric manner.

132 11- 4

Towards durable and broad-spectrum resistance: Post-genomic strategies to understand conserved immune system in land plants

Hidenori Matsui1,2, Izumi Yotsui1, Gang-Su Hyon1, Yuko Nomura1, and Hirofumi Nakagami1

1Plant Proteomics Research Unit, RIKEN CSRS 2Graduate School of Environmental and Life Science, Okayama University

The infection of plants by pathogens is causing a considerable economic loss to agricultural industries. Recent studies estimated that the global yield loss due to biotic stresses averages over 23 percent of the estimated attainable yield across major cereals. An understanding of the fundamental mechanisms underlying disease resistance processes is expected to provide novel ideas for improving the current situation. During the last several decades, extensive analyses revealed that plants utilize a two-branched immune system for defense against pathogens. In the fi rst branch, transmembrane pattern recognition receptors (PRR) are used to recognize and respond to slowly evolving microbe-associated molecular patterns (MAMP). In the second branch, either a direct or an indirect recognition of the pathogen through disease-resistance (R) proteins is used for response to pathogen virulence factors. The R-gene mediated resistance has been widely used in crop improvement. However, the resistance is pathogen race-specifi c and, frequently, a rapid breakdown of the resistance has been reported. Consequently, alternative approaches to provide a broad-spectrum, durable resistance in crops are highly desirable. Meanwhile, several studies have implied that manipulation of the PRR-mediated immune system can be a smart strategy to enhance the broad-spectrum resistance. While extensive genetic screens successfully identifi ed a number of PRRs and components which affect abundance and maturation of PRRs, signal transduction mechanisms that lead to defense responses is thus far limited. This partly stems from limitations of forward genetics caused by lethality and/or genetic redundancy. Accordingly, we have been taking “proteomics” and “comparative genomics” approaches to understand the basic framework of the PRR-mediated immune system. Our recent fi ndings based on “shotgun phosphoproteomics” and studies of an emerging model plant “liverwort Marchantia polymorpha” will be discussed.

133 11- 5

Toward construction of a high-density mutant library in soybean

Akito Kaga

Soybean Applied Genomics Research Unit, National Institute of Agrobiological Sciences

A mutant library with a high mutation density would be helpful for functional studies in soybean and identifi cation of novel alleles useful for soybean breeding. In order to increase the mutation density, seeds of the Japanese elite soybean cultivar ‘Enrei’ were treated with the chemical mutagen ethyl methanesulfonate (EMS) and M2 seeds produced by M1 plants were treated with EMS once again. The resultant library, which consisted of DNA and seeds from 1,536 plants, revealed large morphological and physiological variations. Based on whole- genome re-sequencing analysis of 12 mutant lines, the average number of base changes was 12,796 per line. On average, 691 and 35 base changes per line were missense and nonsense mutations, respectively. Thus, a high mutation density (1 mutation/74 kb) was achieved by repeating the EMS treatment. Development of cost-effective and high-throughput protocols using next generation sequencing (NGS) technologies is expected to simplify the retrieval of mutants with mutations in genes of interest. Indexed amplicon sequencing was designed to retrieve the mutants from the mutant library. In comparison with other screening system, the method allowed one to scan a longer sequence range and discover many mutants with amino acid substitutions without complicated screening steps based on the sequence information of mutation site in the indexed NGS reads. Our mutant library and the indexed amplicon sequencing will be useful for functional studies of soybean genes and have a potential to yield useful mutant alleles for soybean breeding.

NB: This work was supported by a grant from the Ministry of Agriculture, Forestry, and Fisheries of Japan (IVG1005).

134 11- 6

The use of site-specifi c nucleases for plant molecular breeding

Masaki Endo1, Masafumi Mikami2 and Seiichi Toki1,2

1Plant Genome Engineering Research Unit, Agrogenomics Research Center, National Institute of Agrobiological Sciences 2Kihara Institute for Biological Research, Yokohama City University

Genome editing with site-specifi c nucleases allows reverse genetics, genome engineering and targeted transgene integration experiments to be carried out in an effi cient and precise manner. Since vector construction in the CRISPR/Cas9 system is much easier than with ZFNs and TALENs, and because the mutation frequency is relatively high, the CRISPR/Cas9 system is emerging as the major artificial nuclease used for genome engineering. In plants, direct delivery of RNA to plant nuclei is diffi cult. Thus, utilization of appropriate expression constructs for both the single guide (sg) RNA and Cas9 in the CRISPR/Cas9 system is important. Towards establishing an effi cient and universal CRISPR/Cas9-mediated mutagenesis system in rice, we compared mutation frequencies in different Cas9 expression constructs under the same experimental conditions, and determined the optimal constructs (Mikami et al., Plant Mol. Biol.: in press, 2015). By using an all- in-one vector combining the best Cas9 and sgRNA expression constructs, we succeeded in obtaining non-chimeric bi-allelic mutants in regenerated rice plants effi ciently. The CRISPR/ Cas9 system is useful not only for disrupting single genes but also for the creation of large chromosomal deletions by using two sgRNAs (Zhou et al., Nucleic Acid Res. 42: 10903–10914, 2014). Furthermore, using multi sgRNAs, multiplex genome editing has been achieved (Ma et al., doi: 10.1016/j.molp.2015.04.007, 2015). In the case of duplicated genes, disruption of multiple genes is needed to obtain the desired phenotype. We showed that off- target mutations—often cited as a drawback of the CRISPR/Cas9 system—can be used for knockout of multiple paralogous genes in rice (Endo et al., Plant Cell Physiol. 56: 41–47, 2015). Furthermore, induction of DNA double-strand breaks enhances homologous recombination (HR) at the break point. So, when a modifi ed donor DNA is provided with the CRISPR/Cas9 system, repair by HR using this donor DNA will lead to the introduction of the desired sequences at the target site. I would like to discuss the suitability of the CRISPR/Cas9 system for gene targeting in plants, and the further application of this system in precise molecular breeding in plants.

135 NOTE

136 12

Tuesday, September 29 between and UT NTU for Seminar Kick-off the Double Degree Program (DDP) on Bioresource Engineering Venue: Conference Room 402 Kick-off Seminar for the Double Degree Program (DDP) on Bioresource Engineering between UT and NTU

Education and research of biological resource engineering is appearing to play an important role in the development of science and technology or human resources who are internationally active. In the Master’s Program of the biological resource engineering fi eld, an overview of the DDP with UT and NTU is disseminated to interested faculty members and students. The program is scheduled to start from fi scal 2016 (from the UT side).

Session Organizer: Yutaka Kitamura Part One Chair: Motoyoshi Kobayashi, University of Tsukuba Yutaka Kitamura, Junichi P. Abe University of Tsukuba 13:15-13:35 Guidance of DDP between UT and NTU for Global Research & Education Kiyohiko Toyoda Kobe University 13:35-13:55 Several Topics on Quality Evaluation and Safety Assessment of Oils and Fats Using Process Spectroscopic Analysis Suming Chen National Taiwan University 13:55-14:15 The Education and Research in Bio-Industrial Mechatronics Engineering for DDP Part Two Chair: Ryozo Noguchi, University of Tsukuba Yu-Pin Lin National Taiwan University 14:15-14:35 Expectations for Education and Research by DDP in Bioenvironmental Systems Engineering Ting-Jang Lu National Taiwan University 14:35-14:55 Expectations for Education and Research by DDP in Food Science and Technology Tomonori Kume National Taiwan University 14:55-15:15 Towards DDP Joint Research in Foresty and Research Conservation, NTU Part Three Chair: Suming Chen, National Taiwan University Norifumi Hotta University of Tsukuba 15:15-15:35 Lessons Learned from Sediment and Water Dynamics in Mountainous Regions of Japan and Taiwan Toshiharu Enomae University of Tsukuba 15:35-15:55 Development of the Research and Education in Wood and Biomass Fields and Expectations for DDP Ryozo Noguchi University of Tsukuba 15:55-16:15 Expectations for Education and Research by DDP in Food and Bioenergy

137 12-1

Guidance of DDP between UT and NTU for Global Research & Education

Yutaka Kitamura, Junichi P. Abe

Faculty of Life and Environmental Sciences, University of Tsukuba

The Graduate School of Life and Environmental Sciences (as GSLES), University of Tsukuba (as UT) and College of Bioresources and Agriculture (as CBA), National Taiwan University (as NTU) agree to implement “Double Degree Program or DDP” that offers students to receive two Master’s degree diplomas (from UT and from NTU). Under the proposed DDP the qualifi ed graduates who have followed the two years study program successfully will be conferred the two Master’s diplomas from UT and NTU. The diploma awarded by UT is “Master of Agricultural Science or Bioresourse Engineering” and the diploma awarded by NTU is dependent on which program of NTU institutes/departments the graduates have taken. We aim at offering global academic and bioresourse/agricultural education for the students of both graduate schools to encourage them to adapt to a variety of aspects in the international society. We also agree to approve Master’s candidates for diplomas of the UT and NTU for the full formulation and implementation of scientifi c and technical collaboration. Each student in the DDP must have a supervisory committee that consists of two faculty members from the UT and two faculty members from NTU. One faculty member from each university will serve as a co-advisor, and have primary responsibility for the student while the student is at that university. Each student’s supervisory committee must be approved by the UT Provost of GSLES and by the NTU Dean of CBA. UT and NTU students have the opportunity to obtain Master’s degrees from both UT and NTU by spending at least two semesters at the partner institution and by developing substantive research collaboration with a faculty member at the partner institution. The main topics of the DDP are Global Food Security for UT and Bioresources and Agriculture for NTU. In the DDP lectures and seminars should be taught in English. The thesis will be written in English so that the oral defense of the thesis shall be also required and conducted in English at UT or NTU. NTU is the highest educational research institution with a long history and the best academic level in Taiwan and has been ranked at #22 as QS University Rankings in Asia 2015 (July 26, 2015). On the other hand, UT is located at #33 in the same ranking, while taking advantage of the geographic position of Tsukuba Science City and the intellectual accumulation from the 143 years foundation we have continued revolution for the rank up. By growing up of the human resources that can play an active role in the world, we will achieve an improvement of the global evaluation and a further level up of the education and research with through the DDP.

138 12-2

Several Topics on Quality Evaluation and Safety Assessment of Oils and Fats Using Process Spectroscopic Analysis

Kiyohiko Toyoda

Dept. of Agricultural Engineering and Socio-Economics, Grad. School of Agricultural Science, Kobe University

Fats and oils are common constituents of foods and are also effi cient energy depots. Fats and oils in foods are in the form of triacylglycerols (TAG), esters of glycerol and three molecules of fatty acids (FAs). Fatty acid molecules consist of a long chain of carbons. Most of the carbon-carbon bonds in FAs are single bonds, are double bonds in unsaturated FAs. The chain length, unsaturation degree and position vary in diverse FAs. This diversity of FAs provides various properties of TAG. For example, animal fat rich in saturated FAs shows higher melting point than vegetable oils high in unsaturated FAs. Omega-3 and omega-6 FAs have different effects on health, which is attributed to the double bond position in unsaturated FAs. Auto-oxidation reaction of lipids is initiated at dissociation of the double bonds. Therefore, FA varieties and composition ratio of FAs in TAG are effective information for evaluation of food quality and safety. Analysis of FAs has been performed by chemical analysis method such as gas chromatogram, however it requires time consuming and skillful work. Application of spectroscopic analysis methods to foods has been attracted attention to in research and industry as a nondestructive and rapid method. A spectroscopic method is performed by measuring magnetic waves. The induced phenomena in measured objects vary in applied frequencies of magnetic waves. Molecule rotation at radio wave and microwave ranges, vibration of function groups at mid-infrared region, and electron transition and the subsequent reactions at visible and ultraviolet ray regions occur respectively. By measuring these phenomena, the applications for quality evaluation and safety assessment of food can be achieved as follows: detection of adulterated olive oil by dielectric spectroscopy, measurement of FA composition of Japanese Black cattle meat and monitoring of auto-oxidation of fi sh oil by mid-infrared spectroscopy and so on.

139 12-3

The Education and Research in Bio-Industrial Mechatronics Engineering for DDP

Suming Chen

Dept. of Bio-Industrial Mechatronics Engineering, National Taiwan University

The “Bio-Industrial Mechatronics Engineering” (BIME) program integrates the engineering disciplines such as mechanics, electronics, computer science, automatic control, and chemical engineering with applications to bio-industry. The domain of bio-industry covers various fi elds such as agriculture, foods, environment, biological and medical applications, and so on. In the fi elds of bioresource engineering, the BIME department at National Taiwan University (NTU) cooperated with University of Tsukuba (UT) to offer a double degree program (DDP) at the Master degree level. The DDP students will spend a year of graduate study in NTU and UT each respectively. The DDP program consists of curriculum, research and thesis. After fulfi lling the DDP requirements, the students will be conferred the degree of Master of Science in Engineering by NTU in addition to the Master degree from UT. The goal of the BIME program is to prepare students with abilities of independent thinking, analysis, creativity, and integration. The BIME graduate program offers three specialization fi elds: “Machinery and System,” “Measurement and Control,” and “Materials and Process.” Each graduate student should select his/her major fi eld. Each major fi eld has its specifi c core curriculum and elective curriculum, coordinated with students’ research direction. BIME provides multi- engineering disciplines, some of research examples include automation, bio-engineering, bio- sensing engineering, bio-processing, intelligent control, Nano-BioMEMS, biomaterials, bio- informatics, bio-reactor engineering, food engineering, waste treatments, etc. Education and research of bioresource engineering and BIME plays an important role in the development of science and technology for better tomorrow in agriculture, foods, environment, biological and medical sectors. DDP between NTU and UT will defi nitely provide the platform for successful learning and the opportunity to broaden horizons and develop global perspectives for NTU and UT students.

140 12-4

Expectations for Education and Research by DDP in Bioenvironmental Systems Engineering

Yu-Pin Lin

Department of Bioenvironmental Systems Engineering, National Taiwan University

The Department of Bioenvironmental Systems Engineering (BSE) is one of the foundational departments of National Taiwan University (NTU). In its early days, BSE was established as a component of the Agricultural Engineering division with the aim of “Engineering for Survival”. As the rapid development of engineering technology has allowed for humanity’s unprecedented access to Earth’s limited resources and the ability to rapidly change Earth's environment, our focus is now “Engineering for a Sustainable Environment & Quality of Life”. This is necessary since the consequences of anthropogenic environmental change, such as fl oods, droughts, land subsidence, landslides, soil and groundwater pollution, reservoir and river eutrophication, biological habitat dest r uction, etc., th reaten ou r lives, livelihoods, and nat u re as we k now it. To add ress these problems, the integration of science and technology is indispensable. Therefore our main educational and research objectives include the systematic integration of soil and water contamination, information and risk management, bioenvironmental control, and ecological environmental sciences and technologies, all from an environmental systems point of view. Due to the sheer scope of research our department deals with, the BSE program falls into two major categories, which are “Soil and Water Resources Management and Ecological Engineering” and “Sustainable Environmental Planning and Green Building Design”. Students have a chance to choose from a wide range of electives which are sure to fi t their respective fi elds and or interests. The research areas cover water resources management, hazards mitigation, soil and groundwater pollution reduction, irrigation and drainage management, landscape planning, soil, water resources and ecological restoration, vulnerability assessment, adaptive management for climate change, green construction, green energy and carbon sequestration, etc. The BSE department at National Taiwan University (NTU) offers Double Degree Programs (DDP) in conjunction with the University of Tsukuba (UT) for Master’s degree students. The DDP program consists of a curriculum, research and a thesis. The DDP students will spend a year of graduate study at NTU and UT, respectively. After completing the DDP studies, students will receive Master degrees from both NTU and UT. By attending our program, students will have the exciting opportunity to develop cutting-edge knowledge and capabilities in ecological engineering, soil and water resources management, environmental systems and informatics engineering, and the ability to participate in basic research, cross-sectoral research, and international academic research and or projects. Ultimately, our goal is to develop and apply engineering technologies and management science methods to ensure the sustainability of ecological systems and support a sustainable economy. For those students interested in becoming a key player in the necessary changes which will take place during the 21st century, a DDP with NTU and UT will provide a perfect platform for successful learning, strengthening the students’ core skills, and guaranteeing a position in an exciting fi eld.

141 12-5

Expectations for Education and Research by DDP in Food Science and Technology

Ting-Jang Lu

Graduate Institute of Food Science and Technology, University of Taiwan, Taipei, Taiwan (ROC)

Training students to become food scientists equipped with advanced knowledge of food technology, nutrition and health science is the main goal of our education at the Graduate Institute of Food Science and Technology, National Taiwan University. To achieve this goal, GIFST offers master’s and doctoral programs and grouped the curriculum into four related fi elds, biology, physics & chemistry, technology and nutrition & health and bring the latest concepts into the research projects. Students are required to take credits from each fi eld and to complete a research thesis to meet the demands for each graduate degree. Bio-functionality and Techno-functionality of food components has been the main theme of most of the research projects at GIFST in recent years. Bioactive components have been isolated and identifi ed from cereals, herbs and mushrooms, etc. The physiological signifi cance of those components has been demonstrated with in vitro cell-lines or animal models. Analytical methods have been developed to monitor the content of those components in raw materials, the changes in food processing and the stability in fi nal products. Fermentation, biotransformation and nano/submicrosizing processes have been employed to enhance the content, the effi cacy and the stability of those components. Some selected examples are fl avonoid derivatives from aged citrus products, allicin from garlic products, triterpenoids and (1,3) -beta-D-glucans from mushrooms and herbs, polyphenols from Chinese herbs and nanosizing particles of medicinal mushroom. The development of the Double Degree Program in Bioresource Engineering between the University of Tsukuba and National Taiwan University is expected to bring diversity and intercultural competence into both institutions. Basic food science knowledge is a pre-requisite and communication skills using English are required to whom applying for DDP TU-NTU in Food Science and Technology. We hope to construct an international studying environment for the students and bring global aspects into our reseach with through the DDP TU-NTU.

142 12- 6

Towards DDP Joint Research in Foresty and Research Conservation, NTU

Tomoniri Kume

School of Forestry and Resource Conservation, National Taiwan University

Department of Forestry and Resources Conservation was founded in 1925. Our department started to recruit students by dividing into four units. These units are “silviculture”, “resource management”, “forest industry” and “forest resources and conservation”. The department’s educational objectives in accordance with the various units are: (1) Developing professionals for the plantation and conservation of forests who can also use biological technology to improve the quality and productivity of forests (2) Developing professionals for the planning and management of forest resources as well as the environment (3) Developing professionals who have the knowledge of forest product industry as well as soil and water conservation (4) Developing professionals who specialize in forest biological resources and environmental protection. So far, four professors in the department are interested in the DDP program. Dr. Dau-Jye Lu is from the resource management unit. Dr. Wei-Li Liang from the forest resources and conservation units majors Sabo (erosion control as well as soil and water conservation, hillslope hydrology, and soil physics.); interested in soil water movement, vegetation effects, and the mechanisms of sediment movement. Dr. Feng-Cheng Chang from the forest industry section, and his major research scope involves investigating the characterization, processing, and performance of bio-based composite materials. The specifi c research topic is to apply biomaterials such as cellulose and lignin as raw materials combined with the novel technology to develop and innovate advanced fi brous materials and bio-based composite materials. Finally, my research topic it to quantify water and carbon balance in forested ecosystems and determine human impacts on water and carbon cycling. In my presentation, I will share their research scopes and future direction with professors from the University of Tsukuba and promote DDP joint research between Tsukuba and NTU.

143 12-7

Lessons Learned from Sediment and Water Dynamics in Mountainous Regions of Japan and Taiwan

Norifumi Hotta

Faculty of Life and Environmental Sciences, University of Tsukuba

Japan and Taiwan are both mountainous countries, and are both characterized by frequent earthquakes and intensive rainfall induced by typhoons. These earthquakes often cause landslides, leading to sediment deposits in watersheds. This unstable sediment, combined with heavy rainfall events, can result in fl ooding and sediment-related disasters. Therefore, it is crucial to understand water and sediment dynamics in both countries. The 1923 Kanto Earthquake in Japan is still responsible for much of the current sediment discharge in the Tanzawa region; the landslides induced by the earthquake provided huge amounts of sediment in the watershed to be transported, although only during heavy rainfall events (Koi et al., Geomorphology 101, 692–702, 2008). The 1999 Chi-Chi earthquake in Taiwan directly induced numerous landslides, and also reduced slope stability over a wide area of the mountainous region; this also resulted in subsequent landslides, even t riggered by low-intensit y rainfall events (Hotta et al., Journal of the Japan Society of Erosion Control Engineering 58, 3–13, 2005). In both countries, the prolonged infl uence of water and sediment dynamics controls topography (Dadson et al., Nature 426, 648–651, 2003), and consequently determines both land use and conservation. As early as the 1890s, Japan established laws to mitigate fl ooding, based on the concept of forest conservation and erosion control. Climate change will necessitate revisions to land use and conservation strategies, and Japan and Taiwan can both benefi t from sharing their own experiences and knowledge, because both countries share similar characteristics with regard to water and sediment dynamics.

144 12-8

Development of the Research and Education in Wood and Biomass Fields and Expectations for DDP

Yinchao Xu1, Tithimanan Srimongkon1, Evi Oktavia1 and Toshiharu Enomae2

1Grauate school of Life and Environmental Sciences, University of Tsukuba 2Faculty of Life and Environmental Sciences, University of Tsukuba

Wood and paper are representative biomaterials that have been used historically in large quantity. Especially, paper is an industrial product allowing fl exible control of properties on demand. Properties typical of paper such as light weight, liquid transportation, recyclability, and disposability demonstrate a high potential to make various uses other than regular printing and writing performances. Paper electronics is expected to be one of those novel uses and includes, for example, paper sensors such as microfl uidic analytical device to measure concentrations of target components in a test liquid not only visibly but electrochemically. A bioassay system using paper and ink-jet printing was created for bacterial culture tests. Calcium alginate hydrogel, formed by chemical reaction between sodium alginate and CaCl2, was applied. Both of the solutions with nutrients were loaded into ink cartridges and successfully printed simply by outputting CMYK values each based on the demanded amounts of inks to get together on paper. Bacterial cells printed on the hydrogel medium were microscopically observed to be evenly arranged, and the growth of them was successfully achieved. Furthermore, paper- based power generator was fabricated to supply the power to microelectronics embedded on paper. This power generator aims to convert sonic vibration energy into electric energy. A triboelectrically charged polytetrafl uoroethylene sheet and a back electrode were attached to a paperboard. Another paperboard with a counter electrode attached was vibrated in the out-of-plane direction with a mechanical vibrator to simulate sound, voice, or noise-induced vibration. While the vibrated paperboard repeatedly moved toward and away from the other paperboard, the generated voltage between the two electrodes reached 2.3 V. When comb- shaped electrodes were applied, manual strokes in the in-plane direction induced voltage up to 8.2 V. The result suggested that sonic waves could be an electric power source for microelectronics in the future.

145 12-9

Expectations for Education and Research by DDP in Food and Bioenergy

Ryozo Noguchi

Faculty of Life and Environmental Sciences, University of Tsukuba

The main fi eld of the training course on “Food and Bioenergy” in the Environmental Engineering Course of the College of Agro-biological Resource Sciences and the Graduate School of Life and Environmental Sciences, University of Tsukuba, is supported by staff from “Bioproduction and Machinery”, “Agro-Food Process Engineering”, “Bioresource Technology Development”, and “Biomass Conversion Technology Development”. The purpose of the training course is to educate our students who seek to work in the engineering fi eld of agricultural machinery, agricultural facility, food processing, pharmacy production, environmental solution, energy production & utilization, NPO and international organization in mission, philosophy, concept, and production system & technology for added value of food and bioenergy for bright future. The training course covers almost all technologies and its fundamental science education for machines and facilities in agricultural farming, post harvesting, transportation, processing, and refi nement for high added value product. Cascade utilization of bio-resource and energy using cutting edge technology and system analysis from production to waste management is an important program in our “Food and Bioenergy” to attain sustainability based on circulation of material and energy fl ow in the agricultural fi eld and natural resources. Providing advanced technology for sensing and control in the training course is essential to develop student’s ability of design for processing, purifi cation, storage, and transportation in food and bioenergy. In addition, food function science using a microbe, enzyme, biochemical operation, and micronano engineering for physical operations, are indispensable to explore the new technology for our education and research.

146 13

Wednesday, September 30 Understand the and Perspective Future the of Others Imagine to Mathematics of History Education: Mathematics in Hermeneutics Venue: Conference Room 404 Hermeneutics in Mathematics Education: History of Mathematics to Imagine the Future and Understand the Perspective of Others

This session is part of the opening event for the exhibition ‘Wisdom of Mathematics: Exploration and Development’ by the Central Library of the University of Tsukuba from September 28 to November 8, 2015. Mathematicians interpret the development of mathematics to predict future direction and inspire their explorations. Historians interpret the activities of mathematicians in history for knowing the developmental processes with human efforts. Math educators use historical sources as resources in education to imagine the consistent structure and its development beyond generations through reorganization, such as to enable us to understand the perspectives of others until cultivation and appreciation of mathematics beyond just acquiring the pre- established harmony on the system of mathematics. In this session, participants share the mindset of hermeneutic efforts for mathematics education.

Session Organizers: Masami Isoda and Masaru Sanuki Part One Chair for the morning session: Dr. Masaru Sanuki, University of Tsukuba Luis Radford Laurentian University 9:30-9:40 Greetings from the President - History and Pedagogy in Mathematics Masami Isoda University of Tsukuba 9:40-10:00 Hermeneutics as for the Theory of Mathematics Education Universität Bielefeld / Universidade Gert Schubring 10:00-10:45 Federal do Rio de Janeiro Hermeneutics of Historical Mathematics Textbooks 10:45-11:00 Break Wann-Sheng Horng National Taiwan Normal University 11:00-11:45 Thirteenth-Century Chinese Mathematical Texts and their Pedagogical Implications in the 21st Century: The Cases with Suanxue Qimeng and Yang Hui Suanfa Kenji Ueno Yok kaichi University 11:45-12:30 Mathematics of SEKI Takakazu Chair for afternoon session: Shigeru Jyochi, Prof./PhD, Part Two Osaka University of Education Yuriko Yamamoto Baldin Universidade Federal de São Carlos 14:15-14:40 Mathematics and Mathematics Education: The Technology as Strategy of a Hermeneutical Approach of the History of Mathematics to Teach School Mathematics Content Márcia Maria Fusaro Pinto Universidade Federal do Rio de Janeiro 14:45-15:10 Theories of Mathematics Education: Origins and Perspectives for Their Development Shigeru Jochi Osaka University of Education 15:15-15:40 The Manuscript of Yang Hui Suanfa by Seki Takakazu in 1661

147 Panel Discussion 15:45-17:15 Co-Chairs: Masami Isoda, Masaru Sanuki Panelists: Gert Schubring, Wann-Sheng Horng, Kenji Ueno, Yuriko Yamamoto Baldin, Márcia Maria Fusaro Pinto, Shigeru Jochi

148 13-1

Hermeneutics as for the Theory of Mathematics Education

Masami Isoda

CRICED, University of Tsukuba

In Japan, Lesson Study is the reproducible science for teachers to produce good practice for children (Isoda, M., to be published, Dialectic on the Problem Solving Approach: Illustrating Hermeneutics as the Ground Theory for Lesson Study in Mathematics Education. Proceedings of ICME 12, vol. 2: Regular Lectures. Springer) based on their learning from various theories in their communities. Necessary part of LS is the preparation of subject matter to embed the objective for teaching into the content of mathematics and the well prepared class usually goes on with the clear decision making under the teacher’s objective for teaching in relation to the interpretation and assessment of children’s response and their interaction on the content against teacher’s positive questioning. In the LS processes, teachers, students and observers (involving researchers) are trying to understand each other. Here, we call this activity by the technical term ‘hermeneutic efforts’. Through the LS project on the interpretation of the historical textbooks in mathematics (Isoda, M., 2007, Lesson Study in Teacher Education Programs: How do Students Become Teachers That Implement Lesson Study? Isoda, M., Stephens, M., Ohara, Y., Miyakawa, T. edited. Japanese Lesson Study in Mathematics: Its Impact, Diversity and Potential for Educational Improvement. World Scientifi c; Isoda, M. (2015). The Science of Lesson Study in the Problem Solving Approach. Inprasitha, M,. Isoda, M., Wang-Iverson, P., Yeap, B. H. edited. Lesson Study: Challenges in Mathematics Education. World Scientifi c), it is defi ned by the following four activities: ‘just-understanding’, ‘getting the other’s perspective’, ‘self-understanding by the other’s perspective’, and ‘engaging recursively in making the objective knowledge from the subjective knowledge’.

149 13-2

Hermeneutics of Historical Mathematics Textbooks

Gert Schubring

Universidade Federal do Rio de Janeiro

Historical mathematics textbooks provide important tools for research into mathematics education. They can vividly inform about processes how mathematical achievements entered into the domain of school knowledge. They can evidence epistemological conceptions underlying mathematical notions as practiced in different cultures. They can show methodical approaches in teaching mathematics, which might be useful to be studied for adapted adoptions in nowadays teaching – actually, not all what claims today to be new needs to be better! On the other hand, it constitutes quite a challenge to succeed to signifi cant results of historical analysis. In fact, what can be an adapted approach to achieve such results? Evidently, analysing just one textbook cannot yield pertinent results. An example of misleading results of studying just one textbook in an isolated manner is given by the frequent allusions to Alexis-Claude Clairaut’s textbook “éléments de géométrie” from 1741, where Clairaut’s speaking of an alleged approach to detect geometrical truths is misinterpreted as a method of genetic teaching. Apparently, one needs to compare a chosen textbook with others. But what can be the “yardstick”, the “gauge” for the assessment? In an earlier paper on the dominant French textbook author Sylvestre- François Lacroix (1765-1843) I have proposed a three-dimensional approach to achieve pertinent results in textbook analysis: - the fi rst dimension consists in analysing the changes within the various editions of one textbook chosen as the starting-point, say an algebra textbook, or an arithmetic one; - the next dimension consists in fi nding corresponding changes in other textbooks belonging to the same oeuvre, by studying those parts dealing with related conceptual fi elds, say geometrical algebra, trigonometry, etc. - the third dimension relates the changes in the textbooks to changes in the context: changes in the syllabus, ministerial decrees, didactical debates, evolution of mathematics, developments in epistemology, etc. Later on, I have adapted the conception of objective hermeneutics, going back to Schleiermacher, to strive for an interpretation of an historical text, approaching the best the meaning as intended by the historical author. This is a much more promising undertaking as current manners to give just a subjective interpretation. Applying these approaches to a growing number of mathematics textbooks from various cultures and epochs will enrich considerable the theoretical foundations of mathematics teaching.

150 13-3

Thirteenth-century Chinese mathematical texts and their pedagogical implications in the 21st century: The cases with Suanxue Qimeng and Yang Hui Suanfa

Wann-Sheng Horng

Department of Mathematics, National Taiwan Normal University

Suanxue Qimeng (by Zhu Shijie) and Yang Hui Suanfa (by Yang Hui) are, among others, the two most important texts of mathematics which greatly infl uenced how tongsan (Korean mathematics) and wasan (Japanese mathematics) took their shape. Apparently this is the big issue to which historians of mathematics, especially those in East Asia, would pay a lot of attention to despite the fact that both traditions had already well developed on their own. On the other hand, by taking an HPM perspective, these texts can also be introduced into mathematics classes, either in a college liberal study program or in high school, in a very interesting way. In this presentation, I am going to take a few problems from these two texts and explain how HPM perspectives can shed new light to exploring their meanings (both mathematical and historical). As to how teachers implement these endeavors into their classes, I would recommend, as Masami Isoda suggests for the theme of the math education session, an approach underlying which hermeneutics plays a key role. By adopting this approach, teachers would fi rstly engage the students to read carefully the texts in the history of mathematics, then helped them to understand the meaning of the contents, and fi nally sought to make sense of the texts in terms of their historical contexts. In this connection, there is an analogy between teaching situations and historical context. Therefore, the teachers are encouraged to consult not only the students’ cognitive issues but also the historical “stranger’s” view of doing mathematics which is often diffi cult to follow. As a fi nal remark, I will also draw upon the issue of how HPM and the history of mathematics can be benefi cial to each other.

151 13-4

Mathematics of Seki Takakazu

Kenji Ueno

The Seki Kowa Institute of Mathematics, Yokkaichi University

Japanese mathematics of the Edo period started to develop into a new direction beyond Chinese classical mathematics when SEKI Takakazu (1645? - 1708) introduced a method to express algebraic equations of many unknowns (傍書法). Nevertheless, SEKI’s mathematics was based on Chinese classical mathematics. Indeed SEKI studied the Chinese mathematical book “Yang Hui Suanfa” (楊輝算法) carefully and he even composed its revised version. We can fi nd several evidences that SEKI was deeply infl uenced by the “Yang Hui Suanfa”. SEKI was the fi rst mathematician of the East Asian cultural sphere who developed general theories of mathematics. For example, he founded a theory of equations of one known formulating rigorously Horner’s method and more importantly the elimination theory of simultaneous equations of higher degree with many unknowns. Before him an equation had been regarded as only a tool to solve problems and was not the object of mathematical investigations. Although SEKI could not get any information of Western mathematics we can fi nd many similarities with SEKI’s mathematics and Western mathematics at that time. SEKI and the TAKEBE brothers, Katahiro and Kata-akira, who were the best students of SEKI planned to compose the mathematical books, which contain all the results they obtained and also all known results at that time. The fi rst version was completed at the end of the 18th century. But SEKI seemed not satisfactory of the books and he kept a distance from completing the fi nal version. The fi nal version was completed by TAKEBE Kata-akira after SEKI’s death and named “Taisei Sankei” (大成算経) consisting of 20 volumes. In my talk, I will explain about SEKI’s mathematics and its relationship with the “Yang Hui Suanfa” and “Suanxue Qimeng’’ (算学啓蒙).

152 13-5

Mathematics and Mathematics Education: The technology as strategy of a hermeneutical approach of the History of Mathematics to teach school mathematics content

Yuriko Yamamoto Baldin

Departamento de Matemática, Universidade Federal de São Carlos, Brazil

Developing diverse teaching materials for classroom use that conform to the interest and needs of both teachers and students, as well as to the updated curriculum requirements is one of the challenges of current teacher education research. In the process of such development, the History of Mathematics, as a motivation to the learning of mathematics content, is one of powerful strategies for improved teaching. We enhance the hermeneutical approach of introducing and developing school mathematics content with investigative problem solving activities, meaningful from the perspective of History of Mathematics. An interpretation of the historical importance of mathematical problems may depend on the context of the reader as well as the solver, in particular when one considers mathematical problems from different points of view as of a teacher, a mathematician, a professional user of applied mathematics, or even of curious student or ordinary citizen. The hermeneutical approach to rich collection of problems, historically important for the development of mathematics concepts and mathemat- ics as science itself, offers ground to teacher education researchers for deeper refl ections and means to understand the role of problem solving in the context of classroom practice, towards an effi cient learning environment. On the other hand, contemporary educational technologies can enhance this approach, for their use empowers the didactical interpretation of problems, highlights the historical and cultural meanings of problems as well as the curriculum objec- tives of mathematics implied in those problems. We present some examples of didactical material for courses for mathematics teachers, using an interpretative approach to History in a DGS environment. The problem solving steps that enhance the learner´s active participa- tion in the investigation activities constitute innovative teaching strategy that entails teachers´ understanding about the perspective of others.

153 13-6

Theories of Mathematics Education: Origins and Perspectives for Their Development

Márcia Maria Fusaro Pinto

Instituto de Matemática, Universidade Federal do Rio de Janeiro (UFRJ)

Essentially, there are two institutional settings which gave rise to the emergence of theories on mathematics teaching and learning: teacher training for secondary schools and teacher training for primary schools. While the latter setting in many countries were organized in the form of normal schools and enhanced focus on teaching methods and on considering aspects from psychology and pedagogy, the fi rst setting basically provided by universities focused on content knowledge and without regard to the psychological and pedagogical dimensions of learning mathematics. It was within the settings of normal schools that empirical research on learning mathematics performed by psychologists was fi rst accepted for use in teacher training. While this occurred already by the turn of the 19th to the 20th century, further development was quite slow. It was largely due to social movements, which effected the breaking away of social barriers between the separate systems of primary and secondary schooling mainly since the 1960’s. It enabled the creating of professorship for mathematics education at the level of higher education, with the impact of initiating research into mathematics learning and teaching. In the wake of the Royaumont Seminar, organized in 1959 by the OECD, institutes for research into the learning and teaching of mathematics were created in various countries. Eventually, professorships for mathematics education were established within higher education, thus facilitating research in a more extended manner. Most notably, the work of the net of 25 IREM in France, launching several theories with international impact, like théorie des situations didactiques and théorie d‘anthropologie didactique. Yet, today there is not one single general theoretical framework, but a variety of different ones. Michèle Artigue has therefore developed the conception of “theory networking”. Given that the variety of theoretical approaches is largely due to differing national contexts and the problems of mathematics teaching, the perspectives for future development will be in interrelating those aspects of mathematics education, which provide the best adapted intersections, if such exist.

154 13-7

The manuscript of Yang Hui Suanfa by Seki Takakazu in 1661

Shigeru Jochi

International Center, Osaka Kyoiku University

The Yang Hui Suanfa is one of the most important mathematical arts in pre-modern age (from the 13th century to the 19th century) in Eastern Asia. Because the Yang Hui Suanfa had new direction of the mathematics in Eastern Asia, that is to say, speedy calculations for commercial trade, therefore it became the textbook in the Yi dynasty (1392-1910) in Korea. Japanese mathematicians also studied the Yang Hui Suanfa and magic squares, indeterminate equations, and the solving method of higher degree equations although the Yang Hui Suanfa did not describe the established method of higher degree equations, that is, the Tianyuan-shu method. Seki Takakazu (1645?-1708) also studied the Yang Hui Suanfa during his boyhood and hand-copied it in 1661 probably by the wood printed version in Korea. The best version of Yang Hui Suanfa is the wood printed version in Korea and eight books of Yang Hui Suanfa are kept in Japan, Taiwan and Korea. But the Korean version has some mistakes, and Seki Takakazu corrected them. Some opinions said that there were corrected versions in the 17th century. We had the wood printed version and the manuscript of Yang Hui Suanfa at the Yonsei University, Korea. We also found that the corrected points are not the same as Teki Takakazu’s ones. Therefore, we can conclude that the 16 year-old Seki Takakazu corrected mistakes by his own mathematical ability. Seki studied the Yang Hui Suanfa, then he was appointed to Samurai position.

Key Words: the Yang Hui Suanfa, Seki Takakazu, the Yi dynasty, Yonsei University.

155 NOTE

156 14 Engagement in the Olympic and Paralympic Movement

Tuesday, September 29 Venue: Conference Room 300

Engagement in the Olympic and Paralympic Movement

In this symposium, we will discuss our contributions to engagement in the Olympic and Paralympic movement from the perspectives of the academic and scientifi c fi eld. This symposium includes keynote speech by the head of the education project in London 2012 Olympic and Paralympic Games, presentations by high school students from Japan and Brazil, and panel discussion.

Session Organizers: Hisashi Sanada, Yoshio Takahashi, and Fumihiro Kaneko

Part One Chair: Fumihiro Kaneko, University of Tsukuba Kyosuke Nagata University of Tsukuba 13:00-13:10 Opening Remarks Hisashi Sanada University of Tsukuba 13:10-13:15 Introduction of the session Head of Education for the London 2012 Nick Fuller MBE 13:15-13:45 Olympic and Paralympic Games Engagement in the Olympic and Paralympic Movement High School Students from Japan and Brazil 13:45-14:45 What can we do for the 2016/2020 Olympics and Paralympics? 14:45-15:00 Break Part Two Chair: Yoshio Takahashi, University of Tsukuba Panel Discussion: Engagement in the Olympic and Paralympic Movement Panelists: Geert Hendriks, AISTS 15:00-16:20 Kamal Lamichhane, CRICED Kaori Yamaguchi, University of Tsukuba Michel Brousse, University of Bordeaux Toshinori Ishikuma University of Tsukuba 16:20-16:30 Closing Remarks

157 NOTE

158 15 Comparative Study of Architecture between Switzerland and Japan

Tuesday, September 29 Venue: Conference Room 301

Comparative Study of Architecture between Switzerland and Japan

Swiss and Japanese architectural designs have attracted many students’ eyes around the world, but is not a world leading topic. Although both countries cultural background are different from to each other, they have several similarities. The fi rst one is the wood architecture tradition and its craftsmanship. The second one is that young architects and designing trends are supported by society and technology in different ways. The third, which is related to the second point is that society has given to young architects open chances to design, especially for houses as both countries have detached houses sub-culture. Starting from the three points mentioned above, we would like to discuss the similarities and differences of both architectural cultures. As well as in a more analytically way, the signifi cance of comparative studies of each culture on similar aspects of this phenomenon. This discussion could lead and serve as a reference within environmental context regarding to society, culture and education that may be the key to solve those differences.

Session Organizer: Toshihiro Hanazato Part One Chair: Momoyo Kaijima, University of Tsukuba Toshihiro Hanazato University of Tsukuba 9:00-9:20 Introduction to the Session: Why Do We Study Each Others’ Cultures? Takahiko Higuchi Municipal Institute for Historical Research, Iida City 9:20-9:50 Possibility of Conducting Research on Wooden Architecture between Switzerland and Japan Erwin Viray Kyoto Institute of Technology 9:50-10:20 Food and the City: A Collaborative Research Workshop between Kyoto Design Lab and ETH Studio Basel Laurant Stalder ETHZ 10:20-10:50 Environments Here and There: Some Refl ections on Recent Exchanges between Japanese and European Architects

10:50-11:00 Intermezzo

11:00-12:00 Discussion

159 15-1

Possibility of Conducting Research on Wooden Architecture between Switzerland and Japan

Takahiko Higuchi

Municipal Institute for Historical Research, Iida

We believe that a comparative study leads to us not only the mutual understanding but also the profound comprehension of ourselves. Although Swiss and Japan architecture has different cultural background, they have several similarities. Some of the similarities are: the scale of local productions, the passion for traditional techniques in which many young architects and designing trends are supported by society and technology in different ways and fi nally, the craftsmanship. On the other hand, some differences are: the construction of houses, the species of tree and the history after the WWII. In this way, there are also many possibilities of future research topics such as: a) The Vernacular Construction, b) The Westernization of Japanese Style, c) The Early Modernism, d) The Industrial Construction and e) The Applied Traditional T echniques. A good example is The ITAKURA, which literally means the storehouses made of timber board. The ITAKURA could be found all over Japan especially in the areas with plenty wood resources. For example in Nagano Prefecture located North-West from Tokyo city. To conclude, we believe that comparative studies between similar and different aspects of Swiss and Japan culture and architecture will be a potential contribution to strengthen the relations between both countries. In addition, a more analytical discussion could be a useful reference within environmental context regarding to society, culture and education issues that may be the key to solve Swiss and Japan differences.

160 15-2

Food and the City: A collaborative Research Workshop between Kyoto Design Lab and ETH Studio Basel

Erwin Viray

Kyoto Institute of Technology

The metabolism of the city – Energy-Water-Food- Land-Waste – represents some of the material fl ows into and out of our urban space. For the research and design workshop at Kyoto Design Lab we will study food as a means of understanding the larger inputs and outputs of the city, and as a force that allows us to analyze and shape the territorial dimension of the urban condition. How does food shape our cities? How and where is food produced? What is its relationship to water? How does food travel from its place of production, via processing centers into the shops and markets? What kind of waste is produced? How do we feed cities and regions? These are some of the questions that the workshop will be engaged with. The city of Kyoto with the Nishiki Market and the Kyoto Central Wholesale Market will be the fo- cus for the proposed workshop. Our goal is to understand the regional context of Kyoto by analyzing the fl ow of foodstuff for which these two markets act as central nodes. Thematically the workshop will follow the “food chain”. The workshop is structured into three phases, that aim to introduce the students to the topic, research specifi c themes and aspects around the topic of food, and eventually lead to a strategic statement and /or proposal. We seek approximately twelve students, who are committed to engage in this exciting project with us. Participating students will be working in groups of two. The fi rst phase of the study will consist of producing an Atlas which will focus on the precise description and documentation of the existing region of Kyoto in regards to basic parameters such as topography, rivers, climate, gastronomy, etc. The second phase will be a spatial analysis that tackles the Themes and elements of the urban ‘food-chain’ from water via food production and food consumption to waste. This analysis on each theme will be related to either of the two markets in order to channel the research to a more in-depth investigation. The third phase, called Statement, will attempt to trans- form the previously assembled descriptive and analytical phases into a ‘prescriptive’ statement and outlook.

161 15-3

Environments Here and There Some Refl ections on Recent Exchanges between Japanese and European Architects

Laurent Stalder

Professor for the History and Theory of Architecture, Department of Architecture, Swiss Institute of Technology, Zurich (ETH), Switzerland

Japanese architecture has without any doubt been a constant point of reference for Western culture at the least since the late nineteenth century. From the fascination with Japanese crafts- manship to the Modernists’ inquiry into the transparency, fl exibility and constructive logic of traditional Japanese architecture, from contemporary regard for the structural potential of the Metabolists or the spatiality of Shinohara to our own focus at the ETH on the work of Atelier Bow Wow, particularly on its research into the built environment, this interest is manifold. On the one hand, it refl ects a fascination with certain specifi c aspects of Japanese architecture – material, structure, and space – most often viewed through a highly specifi c lens, namely the structural honesty of Modernity, the spatial potential of structure in contemporary design, etc.; on the other hand, this interest encompasses a fantastic system of signs, neither Western nor Japanese, that opens up enormous potential to completely rethink one’s personal understand- ing of architecture. Moreover, this manifold interest is not only common among Western observers of Japan but also has its counterpart among Japanese observers of Western culture. The recent surge of interest in the architectural fi eld in the topic of environment seems a particularly fruitful place to begin analysing the impact of such mutual interest. Brilliantly analysed at the turn of the twentieth century in the work of the Estonian biologist and zoologist Jacob Johann van Ueküll then powerfully reinterpreted over the last fi fteen years in the urban and architectural research of Atelier Bow Wow, this actualisation of the notion of environment, which is especially well expressed in the drawings of the latter Japanese fi rm, has now once again become a major source of inspiration for the younger generation of European architects, most especially because it allows the traditional dualism of Western thought – the building and its users, the natural and the artifi cial, the old and the new, etc. – to be overcome. Such benefi cial “translations” will be analysed in the light of a series of recent projects in Europe and Japan.

162 16 New Realm of Human Biology

Monday, September 28 Venue: Convention Hall 300

New Realm of Human Biology

Human Biology is an interdsciplinary study fi eld, containing biology, medicine, mathematical sciences, and material sciences. In this symposium, we invite the researchers leading human biology in the world and discuss recent advances in human biology.

Session Organizers: Hiroshi Hasegawa, Fuminori Tsuruta, Mitsuo Shoji, Yuji Funakoshi

Akira Shibuya University of Tsukuba 14:15-14:20 Opening Remarks Part I Chair: Mitsuru Okuwaki, University of Tsukuba Arthur D. Lander University of California, Irvine 14:20-14:45 Genome-wide dysregulation and the origins of birth defects Fang-Jen S. Lee National Taiwan University 14:45-15:10 Regulation of Arf GTPase signaling for cell invasive growth: from yeast to humans Patrick C.N. Rensen Leiden University 15:10-15:35 Brown adipose tissue: a novel therapeutic target to combat cardiometabolic disease 15:35-15:45 Coffee break Part II Chair: Mitsuyasu Kato, University of Tsukuba Masaki Kita University of Tsukuba 15:45-16:10 Recent advances in the study of actin-targeting natural products Qing Nie University of Calofornia, Irvine 16:10-16:35 Cell plasticity and multi-step transition in development and cancer Han-Yi E. Chou National Taiwan University 16:35-17:00 Miniature Sample Manipulation for Personalized Medicine Hiroshi Hasegawa University of Tsukuba 17:00-17:05 Closing Remarks

163 16 -1

Genome-wide dysregulation and the origins of birth defects

Arthur D. Lander1,2, Shimako Kawauchi2,3, Rosaysela Santos2,3, Akihiko Muto1,2,4, Shingo Ikeda4, Martha E. Lopez-Burks1,2, Yutaka Kikuchi4, Kyoko Yokomori2,5, Thomas F. Schilling1,2, and Anne, L. Calof2,3

1Department of Developmental & Cell Biology, University of California, Irvine 2Center for Complex Biological Systems, University of California, Irvine 3Department of Anatomy & Neurobiology, University of California, Irvine 4Department of Biological Science, Graduate School of Science, Hiroshima University 5Department of Biological Chemistry, University of California, Irvine

Birth defects are very common causes of mortality and serious disability. Genetic factors are thought to play a major role in birth defects, yet patterns of inheritance are usually com- plex, implicating a polygenic etiology. New insights into the polygenic causes of birth defects are coming from the analysis of syndromes known as “transcriptomopathies”, in which simple genetic changes affect global regulators of transcription, thereby causing simultaneous altera- tions in the expression of large numbers of genes. A particularly good example is provided by Cornelia de Lange Syndrome (CdLS), which is usually caused by haploinsuffi ciency (disrup- tion of one allele) of NIPBL, a gene that encodes a key regulator of cohesin function. Cohesin is a chromatin-associated, multi-protein complex that has increasingly been recognized as essential to the physical interactions of DNA enhancers, promoters and insulators. In NIPBL- haploinsuffi ciency, the expression levels of many hundreds of genes are subtly altered, usually by less than 1.5-fold. Why these sets of genes are affected by partial loss of Nipbl function, and how such small changes in gene expression give rise to birth defects, are among the questions we have recently been addressing, using mouse and zebrafi sh models. Such animal models display a broad range of structural and functional developmental defects remarkably similar to those seen in CdLS, including heart, gut, and limb defects, craniofacial abnormalities, and behavioral disturbances. In this talk I will discuss evidence implicating particular gene-reg- ulatory mechanisms, and particular combinations of transcriptional changes, in the origins of heart and limb defects.

164 16 -2

Regulation of Arf GTPase signaling for cell invasive growth: from yeast to humans

Jia-Wei Hsu1, Kuan-Jung Chen1, and Fang-Jen S. Lee1,2,*

1Institute of Molecular Medicine, College of Medicine, National Taiwan University 2Department of Medical Research, National Taiwan University Hospital

Arf GTPases are critical molecular switches that regulate vesicular traffi cking, cell shape, and movement through conformational changes controlled by nucleotide-binding status. The activation of Arf is under tight spatial and temporal control via Sec7 domain-containing guanine nucleotide exchange factors (GEFs) that catalyze GDP-GTP exchange. GEP100 GEF is responsible for the mammalian Arf6 activation to induce cancer cells invasion and metastasis. Yeast Arf3p, a homologue of mammalian Arf6, is involved in yeast invasion in response to glucose depletion; however, how Arf3p is activated during yeast invasive growth remains unknown. We identify Snf1p as a novel GEF for Arf3p activation when energy is limited. Snf1 is the yeast homologue of AMP-activated protein kinase (AMPK), which is a key metabolic regulator of energy homeostasis, and thus critical for cancer cell growth and yeast invasion. We identifi ed a non-canonical GEF domain located in the conserved regulatory domain of yeast Snf1p and mammalian AMPK that directly binds to and activates yeast Arf3p and mammalian Arf6, respectively. Overexpression of AMPK in 293T cells signifi cantly enhanced Arf6 activation. Surprisingly, yeast Arf3p/mammalian Arf6 activation is independent of Snf1/ AMPK kinase activity. Notably, we found that, in yeast, mutations of the regulatory domain result in markedly reduced Arf3p activation and invasive growth. We also demonstrated that expression of AMPK in snf1Δ cells could complement the raffi nose hypersensitivity and the defective agar invasion. These data provide an evolutionarily conserved survival strategy for eukaryotic cells to activate Arf for invasion during energy depletion. In conclusion, our fi ndings reveal an unexpected function of SNF1/AMPK in cell invasion through Arf GEF activity, in response to energy deprivation. (Hsu J.-W. and Lee F.-J. S., Mol Biol Cell 24: 2328- 2339, 2013. Hsu J.-W., Chen K-J., and Lee F.-J. S. Nature Commun. in press, 2015).

165 16 -3

Brown adipose tissue: a novel therapeutic target to combat cardiometabolic disease

Jimmy F.P. Berbée1,2, Rosa van den Berg1,2, Mariëtte R. Boon1,2, Andrea van Dam1,2, José K. van den Heuvel1,2, Geerte Hoeke1,2, Ingrid M. Jazet1, Takuya Kikuchi1,2, Sander Kooijman1,2, Eline N. Kuipers1,2, Onno C. Meijer1,2, Kimberly J. Nahon1,2, Yanan Wang1,2, and Patrick C.N. Rensen1-3

1Department of Medicine, Division of Endocrinology 2Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center 3Established Investigator of the Dutch Heart Foundation

The research of Prof. Rensen’s group mainly focuses on the role of the brain in lipid and glucose metabolism, and their consequences for obesity, type 2 diabetes (T2D) and cardiovascular disease (CVD). In the beginning of this millennium, brown adipose tissue (BAT) was discovered to be present and functional in adult humans and importantly contributes to energy expenditure by combusting high amounts of glucose and triglycerides into heat. Since BAT is physiologically activated by sympathetic outfl ow from the hypothalamus in the brain, and has great promise as a therapeutic target for obesity, T2D and CVD, BAT became a major focus within this ‘brain-metabolism-T2D-CVD’ research line since 2010. Initially, we observed that South Asians who are particularly prone to develop T2D and CVD, have low BAT activity correlating with decreased energy expenditure (Lancet Diabetes Endocrinol 2014), consistent with the hypothesis that low BAT activity may cause an adverse metabolic phenotype. We demonstrated how BAT activation infl uences lipoprotein metabolism (J Lipid Res 2015), and elucidated several targets in the brain as well as in BAT that increase BAT activity, including the melanocortin 4 receptor (J Lipid Res 2014), cannabinoid receptor 1 (FASEB J 2014), AMPK (Diabetes 2014) and the GLP-1 receptor (submitted). We showed that BAT activation improves dyslipidemia, glucose tolerance, T2D, and even atherosclerosis (Nat Commun 2015). We currently also investigate the role of the immune system (Diabetes 2015) and the biological clock (PNAS USA 2015) in BAT function, and attempt to discover biomarkers for BAT activity, by combining intervention studies with the large Netherlands Epidemiology of Obesity (NEO) cohort. We just initiated BAT-targeted intervention studies in humans to elucidate whether BAT activation improves cardiometabolic health.

166 16 -4

Recent advances in the study of actin-targeting natural products

Masaki Kita

Graduate School of Pure and Applied Sciences, University of Tsukuba

Actin is an essential cytoskeletal protein for the regulation of various cellular functions. A number of actin-stabilizing and depolymerizing agents have been discovered in marine invertebrates, and they show potent cytotoxicity. Among them, a polyketide macrolide aplyronine A has antitumor effects against xenograft in mice (Yamada K et al., J Am Chem Soc 115: 11020-11021, 1993; Yamada K et al., Nat Prod Rep 26: 27-43, 2009). However, the potent cytotoxicity and apoptogenic effect of aplyronine A was not entirely accounted for by its actin fi lament-severing properties, and its molecular targets and mechanisms of action remained unclear. We developed aplyronine A acetylene or biotin derivatives that bear an aryldiazirine group at the C34 terminus, which formed a covalent bond with actin (Kita M et al., Angew Chem Int Ed 50: 9871-9874, 2011; Kita M et al., J Am Chem Soc 134: 20314-20317, 2012). By using these chemical probes, we have showed that aplyronine A synergistically binds to tubulin in association with actin, and prevents spindle formation and mitosis in tumor cells (Kita M et al., J Am Chem Soc 135: 18089-18095, 2013). Several tubulin-targeting natural products, which regulate spindle microtubule dynamics, have been widely used in cancer chemotherapy. To our knowledge, aplyronine A (1) is the fi rst molecule to be known to promote the protein– protein interactions (PPIs) between tubulin and actin to exert highly potent biological activities (Kita M and Kigoshi H, Nat Prod Rep 32: 534-542, 2015). Our fi ndings of aplyronine A will provide further insights into the molecular mechanisms of structurally diverse natural products that regulate cytoskeletal dynamics. The complexity and diversity of natural products might lead to multiple interactions with as-yet-unidentifi ed intracellular biomolecules, such as motor proteins and signaling molecules. The use of PPI-stabilizing or -inhibiting scaffolds could have important implications for simplifi ed mimetic design, and also provides new insight into ways to design molecules that tether proteins using different binding surfaces.

167 16 -5

Cell plasticity and multi-step transition in development and cancer

Qing Nie

Center for Complex Biological Systems Department of Mathematics and Department of Biomedical Engineering, University of California, Irvine

Reversible epithelial-to-mesenchymal transition (EMT) is central to tissue development, epithelial stemness, and cancer metastasis. While many regulatory elements have been identifi ed to induce EMT, the complex process underlying such cellular plasticity remains poorly understood. Utilizing a systems biology approach integrating modeling and experiments, we found multiple intermediate states contributing to EMT and that the robustness of the transitions is modulated by transcriptional factor Ovol2. In particular, we obtained evidence for a mutual inhibition relationship between Ovol2 and EMT inducer Zeb1, and observed that adding this regulation generates a novel four-state system consisting of two distinct intermediate phenotypes that differ in differentiation propensities and are favored in different environmental conditions. We identifi ed epithelial cells that naturally exist in an intermediate state with bidirectional differentiation potential, and found the balance between EMT-promoting and -inhibiting factors to be critical in achieving and selecting between intermediate states. Our analysis suggests a new design principle in controlling cellular plasticity through multiple intermediate cell fates and underscores the critical involvement of Ovol2 and its associated molecular regulations.

168 16 - 6

Miniature Sample Manipulation for Personalized Medicine

Li-Yu Chen1, Wei-Feng Fang2, Tsao-Chun Huang2, Yi-Fan Yu2, Jing-Tang Yang2, and Han-Yi Chou1

1Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University 2Department of Mechanical Engineering, College of Engineering, National Taiwan University

The advent of personalized medicine brought exiting innovations in health care and research, however, the diffi culty of specimen manipulation at miniature scales soon emerged as a primary constrain, as subject derived samples should always be minimalized as to preserve donor integrity and to enable longitudinal analyses. To tackle this problem, microfl uidics engineering offers great opportunities, by providing with theoretical analyses and maneuvering technology at nano- and microliter sizes. We designed and fabricated a microfl uidic device for bed-side fractionation of cells, featuring temperature control, bicarbonate dependent pH regulation, and a pH responsive chitosan coating to discriminate cancer metastatic potential through absorption of fi bronectin. We show that cell absoption/detachment in our design correlates with the migratory ability of lung and oral squamous cell carcinoma upon change of physiologically permissible range of environmental pH, without the need of cell culture facilities and time-consuming maneuvers for the assay. The working scale requires minimal amount of cells, which may be obtained by operation and even biopsy. The second example is an enabling demonstration of open-surface droplet manipulation, which explores the dynamicity of droplet behavior to couple with matching-score dependent hybridization to drive controlled growth of nanogold structures. Systematic comparison of the different possible matchings then lead to a colorimetric read out that can be judged with the naked sight. This concept is compatible with homecare diagnosis coupled with cloud sourcing to enable early detection of drug resistance in cancer.

169 NOTE

170 17 Systems Biology Café

Tuesday, September 29 Venue: Conference Room 406

Systems Biology Café

Center for Complex Biological Systems (CCBS) in University of California, Irvine, is one of the most important partner organizations of Ph.D. Program in Human Biology (HBP), University of Tsukuba. In this session, we will have a talk of cutting-edge research related to systems biology from CCBS professor, Dr. Hughes, to discuss future development of human biology.

Session Organizer: Hiroshi Hasegawa

Chair: Arthur D. Lander, University of California, Irvine Christophar C.W. Hughes University of California, Irvine 12:00-13:15 Body-on-a-chip: At the interface between physiology, engineering and systems biology

171 17-1

Body-on-a-chip: at the interface between physiology, engineering and systems biology

Christopher C. W. Hughes, Ph.D.

Depts. Molecular Biology & Biochemistry, and Biomedical Engineering, University of California, Irvine

There is a growing interest in creating microphysiological systems that can accurately predict the responses of humans to drugs or potential toxins. While mice have proven extremely useful for these applications their physiology is often markedly different to human and predictions have often proven to be disastrously inaccurate. We have created vascularized micro-organs in microfl uidic devices and have focused particularly on vascularized microtumors (VMTs). Although cancer is a heterogeneous disease, current chemotherapy is based on the use of anti-cancer agents that broadly affect cell proliferation. Consequently, this non-specifi c tumor therapy often leads to high toxicity and therapeutic resistance, which increases the risk of disease progression. There is thus a critical need to fi nd novel anti- cancer compounds. However, as a result of preliminary screens that are performed in 2D systems, and the use of mouse models for secondary screens, many drugs fail during full clinical trials. Replicating a complex, 3D microenvironment incorporating human cells is therefore likely to improve drug screening effi ciency. We have developed a novel system that features 3D tumor tissues incorporating human cells co-cultured with stromal cells and connected by human microvessels in a naturally occurring 3D matrix in a PDMS microdevice. Transduced colorectal cancer (CRC) cells that constitutively express green fl uorescent protein (GFP) are introduced into the device in co-culture with human endothelial cells (EC) and fi broblasts (transduced with mCherry and Blue-FP, respectively). A vascular network forms within 7 days, and medium and drugs are delivered through this network, driven by a hydrostatic pressure gradient. CRC cells show continuous growth, receiving their nutrients through the vasculature. Tumors growing in the device respond differently to drugs compared to cells growing in 2D. We have identifi ed cytotoxic and cytostatic drug actions in the device with IC50s close to the in vivo pharmacologic plasma concentration, but higher than those obtained in parallel 2D experiments. Importantly, we also identifi ed drugs that were active in our 3D-device but not in 2D cultures. In conclusion, preliminary results using our 3D microphysiological system, in which we have created a more complex microenvironment than used in 2D cultures, support an improved strategy for drug validation. Future experiments will involve the use of non-invasive optical imaging techniques to better understand the human 3D tumor microenvironment, including the study of different tumor behaviors, tumor metabolism, metastasis, and pathological angiogenesis.

172 18 Imaging Science Café - for Biology and Medicine

Tuesday, September 29 Venue: Conference Room 406

Imaging Science Café - for Biology and Medicine

Recent advances in imaging technologies are essential for the development of clinical medicine and basic biology/medicine. In this symposium, the activities toward the imaging techniques in biological/medical fi eld in the partner universities are introduced and discussed for possible collaborative researches.

Session Organizers: Ryosuke Ohniwa, Yuichi Kimura, and Hiroshi Hasegawa Introduction of Activities Part I Chair: Hsinyu Lee, National Taiwan University Akira Shibuya University of Tsukuba 18:05-18:10 Remarks from the Ph.D. Program in Human Biology Satoru Takahashi University of Tsukuba 18:10-18:25 In vivo image analysis using iRFP transgenic mice Tzu-Ming Liu National Taiwan University 18:25-18:40 In vivo leukocyte imaging with multiphoton fl uorescence and harmonic generation microscopy Kentaro Hatano University of Tsukuba 18:40-18:55 Synthesis System for PET Radiopharmaceutical Dedicated to Boron Neutron Capture Therapy Vincent Dousset University of Bordeaux 18:55-19:10 Translational research for the understanding of early cognitive impairment in patients with neuro-infl ammatory diseases Arash Kheradvar University of California, Irvine 19:10-19:25 Volumetric Echocardiographic Particle Image Velocimetry (V-Echo-PIV) Discussion for Possible Collaboration Part II Chair: Tsai-Kun Li, National Taiwan University Topic 1 - Collaboration toward clinical application 19:25-19:50 Topic 2 - Collaboration in the development of bioimaging technology Topic 3 - Co-education Ryosuke Ohniwa University of Tsukuba/National Taiwan University 19:50-19:55 Closing Remarks

173 18-1

In vivo image analysis using iRFP transgenic mice

Satoru Takahashi1~4, Mai Thi Nhu Tran1,4, Junko Tanaka1,4, Michito Hamada1,4, Yuka Sugiyama1,4, Shota Sakaguchi1,4, Megumi Nakamura1,4, Yoshihiro Miwa1,4

1Department of Anatomy and Embryology, Faculty of Medicine 2International Institute for Integrative Sleep Medicine (WPI-IIIS) 3Life Science Center, Tsukuba Advanced Research Alliance (TARA) 4Laboratory Animal Resource Center (LARC), University of Tsukuba

Fluorescent proteins with light wavelengths within the optical window are one of the improvements in in vivo imaging techniques. Near-infrared (NIR) fl uorescent protein (iRFP) is a stable, nontoxic protein that emits fl uorescence within the NIR optical window without the addition of exogenous substrate. However, studies utilizing an in vivo iRFP model have not yet been reported. We have generated transgenic iRFP mice with ubiquitous NIR fl uorescence expression. iRFP expression was observed in approximately 50% of the offspring from a matings between iRFP transgenic and WT mice. The serum and blood cell indices and body weights of iRFP mice were similar to those of WT mice. Red fl uorescence with an excitation wavelength of 690 nm and an emission wavelength of 713 nm was detected in both newborn and adult iRFP mice. We also detected fl uorescence emission in whole organs of the iRFP mice, including the brain, heart, liver, kidney, spleen, lung, pancreas, bone, testis, thymus, and adipose tissue. Therefore, iRFP transgenic mice may therefore be a useful tool for various types of in vivo imaging. I will discuss possible application about iRFP.

174 18-2

In vivo leukocyte imaging with multiphoton fl uorescence and harmonic generation microscopy

Cheng-Han Wu1, Ming-Rung Tsai2, Chien-Kuo Chen1, Cheng-Kun Tsai1, Pi-Tai Chou2, and Tzu-Ming Liu1,3

1Institute of Biomedical Engineering, National Taiwan University 2Department of Chemistry, National Taiwan University 3Molecular Imaging Center, National Taiwan University

In vivo study of leukocytes is challenging due to its nature of fast traffi cking, multiple lineages, frequent cell-cell interactions, and dynamic activation or maturation in a process of immune response. People commonly used confocal or multiphoton fl uorescence microscopy to label cells and study in vivo dynamics and microenvironments of immune system at a high spatial and temporal resolution. But for future clinical application, a labeling free method is required. Recently, without a labeling, we demonstrated that granules in leukocytes have distinctive third harmonic generation (THG) contrast. Excited by a 1230nm femtosecond laser, THG signals were generated at a signifi cantly higher level in neutrophils than other mononuclear cells, whereas signals in agranular lymphocytes were one order smaller. These characteristic THG features can also be observed in vivo to trace the newly recruited leukocytes following lipopolysaccharide (LPS) challenge. Furthermore, using video-rate THG microscopy, we also captured images of blood cells in human capillaries. Quite different from red-blood-cells, every now and then, round and granule rich blood cells with strong THG contrast appeared in circulation. The corresponding volume densities in blood, evaluated from their frequencies of appearance and the velocity of circulation, fall within the physiological range of human white blood cell counts. These results suggested that labeling-free THG imaging may provide timely tracing of leukocyte movement and hematology inspection without disturbing the normal cellular or physiological status.

175 18-3

Synthesis system for PET radiopharmaceutical dedicated to boron neutron capture therapy

Kentaro Hatano1,2, Yasunori Tokuda1,2,3 and Motohiro Sato2

1Faculty of Medicine, University of Tsukuba 2Tsukuba Molecular Imaging Center 3Proton Medical Research Center, University of Tsukuba

Tsukuba Molecular Imaging Center was founded on Nov. 2012. This center was primarily focusing on clinical cancer diagnosis with 18F-fl uorodeoxy-D-glucose (FDG). We have conducted about 500 FDG production and 5000 scans from the opening to Dec. 2014. Our main equipments were shown in Table 1. University of Tsukuba has been developing neutron source for boron neutron capture therapy (BNCT) utilizing linac proton accelerator (Kumada H et al., Appl Radiat Isot 88: 211- 215, 2014). Two major pharmaceuticals, L-BPA and BSH, have been used for BNCT and for therapy with L-BPA localization and grading of tumor by PET scan with FBPA, a 18F labeled congener of L-BPA, was regarded essential. We have just installed special radiosynthesis system for FBPA which was developed in collaboration with Dainippon Seiki (DNS). This system was designed to produce FBPA through two different pathways, original method 18 utilizing F-F2 gas as labeling reagent (Ishiwata K et al., Appl Radiat Isot 42: 325-328, 1991) and fairly modern method starting from 18F-fl uoride. As up-to-date cyclotrons accelerate 18 only proton, we should employ double irradiation method to afford reactive F-F2 gas from 18O(p,n)18F reaction (Bishop A et al., Nucl Med Biol 23: 189-199, 1996). This method consists 18 18 of F production by proton irradiation of O-O2 gas followed by another proton irradiation 18 for isotopic exchange and recovery of F2. Optimized procedure will be discussed in detail.

Table 1 Equipments in Tsukuba Molecular Imaging Center Imaging MRI MAGNETOM Avanto 1.5T Siemens CT SOMATOM Emotion Excel-Edition16 Siemens PET-CT True Point Biograph16 Siemens PET-CT Biograph mCT Siemens Production Cyclotron Eclipse HR Siemens FDG Production Explora FDG4 (Two Systems) Siemens Florbetapir NEPTIS ORA Production 11C/18F- Multipurpose Synthesizer DNS 18 18 - F2/ F FBPA Synthesizer DNS

176 18-4

Translational research for the understanding of early cognitive impairment in patients with neuro-infl ammatory diseases

Vincent Planche1,2, Thomas Tourdias1,2, and Vincent Dousset1,2

1University of Bordeaux, CHU of Bordeaux, Translational Research and Advanced Imaging Laboratory 2INSERM U862 and University of Bordeaux NeuroSciences Magendie Center, Bordeaux

Patients suffering from neuro-infl ammatory diseases (Multiple Sclerosis, Lupus, …) are often (40 to 60%) affected early on during the course of the disease by cognitive disorders that are strongly impairing their daily life. Information processing speed and long term memory are the most consistently impaired function in multiple sclerosis. Diffuse brain damages, global atrophy or disconnection have appeared to be related to the cognitive disorder onset. Hippocampus atrophy is a late consequence of previous physiopathological mechanisms that remain unknown, thus preventing to try specifi c treatments. Since brain biopsies are non- ethically available and no blood biomarker is available, our fi rst goal was to capture early hallmarks of hippocampus abnormalities using non-conventional MRI technics in human beings. Our second goal was to study on an animal model of neuro-infl ammation the pathophysiological mechanisms leading to hippocampal atrophy in a neuro-infl ammatory mouse model experimental acute encephalomyelitis (EAE). In a group of 70 patients we confi rmed a rate up to 69% of abnormal information processing speed and even a rate of 27% of verbal episodic memory impairment in patients recently diagnosed of neuro-infl ammation. However most of the patients did not show hippocampal atrophy on MRI studies. By refi ning a non conventional-MRI method called diffusion tensor imaging (DTI), we were able to discriminate the microstructural changes in the hippocampus of the affected patients and the DTI measures revealed signifi cant correlations with memory impairment in the patients recently diagnosed of neuro-infl ammation. To understand the biological substrate we fi rst demonstrated an early hippocampal-dependent memory defi cit in EAE mice. MRI studies at 4.7 Tesla of the mice brain revealed no atrophy of the hippocampus, however microstructural modifi cations in some hippocampal layers using dedicated DTI methods. Histological correlates revealed a selective and early neurodegenerative process. Electrophysiological recording studies confi rmed the differential neuritic/synaptic vulnerability in specifi c layers of the hippocampus. In vivo DTI correlates with early microstructural changes, appeared more sensitive than MRI measures of atrophy, and could be used as a biomarker of therapeutic response in human beings.

177 18-5

Volumetric Echocardiographic Particle Image Velocimetry (V-Echo-PIV)

Ahmad Falahatpisheh1,2 and Arash Kheradvar1,2

1Department of Biomedical Engineering, University of California, Irvine 2Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California, Irvine

Background: Currently, matrix array probes with 3D acquisition capability have not yet been employed for 3D vector characterization of blood fl ow. Here, for the fi rst time, we introduce a novel method that generates velocity vector fi eld in 4D based on volumetric echocardiographic images needless of contrast agent. Methods: We developed an in-house computer program that processes volumetric echocardiographic images by solving the transport equation of brightness fi eld in 3D over time and computes 3D velocity vector fi eld. Instead of using contrast agent, the blood speckles are used as tracer particles. The brightness transport equation was solved in a least square sense in proper interrogation window sizes in consecutive volumetric frames. As a test for predicting complex 3D rotational fl ows, several synthetic volumetric brightness fi elds were generated and processed. After development and validation, volumetric echo DICOM of adult healthy human left ventricles were processed. This set of 3D data was acquired without using any contrast agent by a 4V GE ultrasound matrix array transducer, with temporal resolution of 21.5 ms and a voxel size of 0.9×0.6×0.9 mm3. Results: The expected velocity fi elds were successfully predicted by V-Echo-PIV in all the studied cases. Figure 1A illustrates a snapshot of the VolDICOM of the raw data before processing with V-Echo-PIV. Figure 1B illustrates the results of V-Echo-PIV including the 3D velocity vector fi eld, and rotational streamlines bounded within the LV wall during early systole. Conclusion: In this work, we showed a method to characterize and visualize blood fl ow in 3D based on volumetric images of human heart using no contrast agent. This novel imaging modality provides three-dimensional fl ow data without the hassle of injection of contrast agent, and is particularly advantageous for studies that involve pediatric population where the safety and effectiveness of contrast agents is not yet established.

178 19 NTU Lounge

Tuesday, September 29 Venue: Conference Room 406

NTU Lounge

By introducing current research and educational activities in National Taiwan University, international relashionship among partner universities are expected to be strengthened.

Session Organizer: Ryosuke Ohniwa Chair: Fang-Jen Lee, National Taiwan University Luisa Shu-Ying Chang and Fang-Jen Lee National Taiwan University 17:15-17:20 Opening Remarks Wen-Yih Isaac Tseng National Taiwan University 17:20-17:35 Introduction of NTU Molecular Imaging Center Hsiang-Kuang Liang National Taiwan University 17:35-17:50 NTU Proton Therapy Center Meng-Tsz Tsai National Taiwan University/University of Tsukuba 17:50-18:05 Campus life in National Taiwan University and University of Tsukuba

179 NOTE

180 20 Life and Medical Sciences in Southeast Asia

Wednesday, September 30 Venue: Conference Room 402

Life and Medical Sciences in Southeast Asia

Globalization of the University of Tsukuba is seeing a dramatic increase in the number of students from Southeast Asian countries. In this session, invited professors and graduate students from partner universities and institutes in these countries join the graduate students of the University of Tsukuba to present and discuss their latest research.

Session Organizer: Koji Hisatake

Part One Chair: Koji Hisatake, University of Tsukuba Kazuya Morikawa University of Tsukuba 14:15-14:30 Natural competence for DNA transformation in Staphylococcus aureus Septelia Inawati Wanandi Universitas Indonesia 14:30-14:45 Modulation of extracellular pH of human breast cancer stem cells (CD24-/ CD44+) as a novel strategy for breast cancer therapy Dang Thi Phuong Thao HCMC University of Science 14:45-15:00 Ethnomedicine of some ethnic minorities in Vietnam: from use to study Rizky Abdulah Universitas Padjadjaran 15:00-15:15 Bioactive compounds isolated from primates-consumed plants for human disease therapy Dong Van Quyen Institute of Biotechnology Highly pathogenic avian infl uenza virus A/H5N1: genetic evolution and 15:15-15:30 protective effi cacy of NIBRG-14 vacccine against the virus strains circulating in Vietnam Ni Nengah Dwi Fatmawati Universitas Udayana 15:30-15:45 Capsular typing of Streptococcus pneumoniae clinical isolates in Bali 15:45-15:50 Discussion Part Two Chair: Kiong Ho, University of Tsukuba Thi Kim Lien Pham University of Tsukuba 15:55-16:10 Analysis of Scd6 physiological activity through its interaction with Hmt1 Syarifah Dewi Universitas Indonesia 16:10-16:25 Gene expression profi le of p53 apoptotic pathway genes in advanced breast cancer isolated from Indonesian patients after neo-adjuvant therapy Riezki Amalia University of Tsukuba 16:25-16:40 Novel functional domain in human TMEPAI Huynh Man Anh HCMC University of Science 16:40-16:55 Drosophila duch knockdown as a potential model for studying Parkinson’s disease pathogenesis and screening therapeutic antioxidants

181 Bui Phuong Linh University of Tsukuba 16:55-17:10 Mechanism of X chromosome reactivation during reprogramming

17:10-17:15 Discussion

182 20-1

Natural competence for DNA transformation in Staphylococcus aureus

Kazuya Morikawa1, Nguyen Thi Le Thuy1, Aya Takemura1, Ryosuke Ohniwa2, Tarek Msadek 3.

1Microbiology, Faculty of Medicine, University of Tsukuba 2Center for Biotechnology, National Taiwan University, University of Tsukuba Taiwan offi ce 3Biology of Gram Postive Pathogens, Institut Pasteur

Staphylococcus aureus is a major human pathogen responsible for a broad spectrum of infections, emphasized by the emergence of multiple antibiotic-resistant strains with up to 60% of strains worldwide resistant to methicillin (Methicillin Resistant Staphylococcus aureus or MRSA). Many bacteria have the ability to acquire novel genetic characteristics, including antibiotic resistance, through the uptake of extracellular DNA, a phenomenon known as natural genetic transformation or competence. We have shown that the SigH staphylococcal sigma factor is a key component for competence development, and uncovered two distinct mechanisms allowing activation of SigH production in S. aureus subpopulation: a chromosomal gene duplication rearrangement and post-transcriptional regulation through an upstream inverted repeat sequence. Importantly, we have demonstrated for the fi rst time that S. aureus cells producing active SigH become competent for natural transformation by plasmid or chromosomal DNA, and we were able to confer methicillin resistance to a methicillin-sensitive strain by transformation with chromosomal DNA. SigH-dependent competence development in S. aureus could help explain the acquisition of antibiotic resistance genes and the rise of the so-called ‘‘superbug.’’

183 The expression of CD133 gene in primary glioma cells isolated from Indonesian patients and its correlation with pluripotency, hypoxia and tumor grade

Septelia Inawati Wanandi1, Novi Silvia Hardiany1, Febrial Hikmah2, Radiana Dhewayani Antarianto3, and Syaiful Ichwan4

1Department of Biochemistry and Molecular Biology, Faculty of Medicine, Universitas Indonesia 2Master Program in Biomedical Science, Faculty of Medicine, Universitas Indonesia 3Department of Histology, Faculty of Medicine, Universitas Indonesia 4Neurosurgery Division, Department of Surgery, Faculty of Medicine, Universitas Indonesia

Glioma is the major primary brain tumor with frequent therapeutic resistance. According to WHO (2007), human glioma can be histopathologically classified into low-grade (grade I and II) and high-grade (grade III and IV). Glioma stem cells (GSCs) were considered to play a role in the therapy resistance and disease recurrence of human glioma. GSCs can be recognized by the expression of CD133 surface antigen marker and pluripotent protein, such as Oct4. Like most of normal stem cells, GSCs prefer to grow in hypoxic condition of tumor niche which might be required to maintain their stemness. Therefore, the aim of this study is to analyse the relevance of tumor grading and hypoxia identification for GSCs detection. Glioma specimens that obtained from 35 Indonesian patients after surgery comprised of 20 low-grade and 15 high-grade tumor. Expression of mRNA CD133, HIF-1α and Oct4 were relatively measured using qRT-PCR normalized to 18S rRNA. HIF-1α protein expression was detected by immunohistochemistry. The expression of CD133 and Oct4 mRNA, as well as HIF-1α protein was significantly higher in high-grade compared to low- grade glioma. There was also a significant positive correlation between CD133 and Oct4 mRNA expression (r = 0.518, p<0.05), as well as between CD133 and HIF-1α (r = 0,513, p<0.05) in high-grade - but not in low-grade - glioma. Hence, we conclude that the presence of GSCs could be clearly identified in high-grade glioma and correlated well with tumor hypoxia. Further studies are required to determine the cut-off point of CD133, Oct4 and HIF-1α expression in human glioma for therapy monitoring.

184 20-3

Ethnomedicine of some ethnic minorities in Vietnam: from use to study

Dang Thi Phuong Thao

Department of Molecular and Environmental Biotechnology, Faculty of Biology, University of Science, Vietnam National University - Ho Chi Minh City

Vietnam has a high diversity of plants among those a lot with medicinal properties. Many Vietnamese, especially ethnic minorities people in Vietnam, have custom in using herbal plants for treating diseases. We so far have collected about 112 different ethno-medicinal plants in Bidoup National Park, Lam Dong, Vietnam. Our surveyed data revealed that the medicinal plants are used for treatment 79 types of health problem including 52 ailments in human and 4 in animals mostly for digestive, dermatological and infectious or immune related ailments in human. Many different parts of medicinal plant are used; in which rhizomes (including bulb) are the most commonly part (22.8%), followed by leaves (22.2%) and roots (including tuberous roots). Fresh material is preferred to use than dried one (87.8% versus 12.2%), and most of the plants are used directly without preparation (25.5%), then by crushing (23.7%) and hot maceration. In most cases, the traditional knowledge of ethnic minorities is passed verbally from generation to generation and most of fathers are responsible in transmitting medicinal knowledge. The transmission begins in the early life stages, about 15 years old. The medicinal plants and related traditional knowledge are facing serious problems such as the agricultural expansion, the neglect of young generation, the change of socio-economic, etc. Our experimental data on some medicinal plants also revealed that some plants are highlighted as potential candidate in wound healing, diarrheal and cancer treatment.

185 20-4

Bioactive compounds isolated from primates-consumed plants for human disease therapy

Rizky Abdulah1, Ajeng Diantini1, Unang Supratman2 and Anas Subarnas1

1Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Indonesia 2Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Indonesia

Non-human primates and humans have a high degree of physiological similarity. Futhermore, primate disease often exhibits similarities to human disease, and certain human diseases are known to have originated from primates. Notably, since primate survival largely depends on daily food intake, plants consumed by non-human primates represent potential drug sources for human disease therapy. In recent years, we have focused our investigations on discovering bioactive compounds from plants commonly consumed by primates, especially their anticancer, antimalarial, and antibacterial properties. Leaves of 42 plant species that commonly consumed by non-human primates were collected from Pangandaran Beach Conservation Area of West Java, Indonesia. Their anticancer, antimalarial and antibacterial properties were screened in vitro to MCF-7 human breast cancer cell lines, chloroquine- resistant Plasmodium falciparum, and gram-negative bacteria Escherichia coli – gram positive bacteria Bacillus subtilis, respectively. The active compounds of the leaves of potential plants were subsequently isolated using column chromatography and identifi ed by nuclear magnetic resonance. From all the plants tested, Dysoxylum caulostachyum, Eugenia aquea, Schima wallichii, and Garcinia celebica shows the most potential anticancer properties; Pandanus nitidus, Eugenia aquea, Schima wallichii, and Garcinia celebica shows the most potential antimalarial properties; Kleinhovia hospital, Dillenia excelsa and Garcinia celebica shows the most potential antibacterial properties against gram-negative bacteria Escherichia coli; while Ficus benjamina, Ficus altissima, and Elaecocarpus glabra shows the most potential antibacterial properties against gram positive bacteria Bacillus subtilis. From those potential plants, we isolated and identifi ed kaempferol-3-O-rhamnoside; 2’,4’-dihydroxy-6-methoxy- 3,5-dimethylchalcone; methyl-3α,23-dihydroxy-17,14-friedolanstan-8,14,24-trien-26-oat as the active anticancer compounds, and kaempferol-3-O-rhamnoside and catechin as the active antimalarial compounds. While the active antibacterial compounds is still under identifi cation in our laboratory. These results provide a basis for the potential use of non-human primates- consumed plants in human diseases therapy.

186 20-5

Highly pathogenic avian infl uenza virus A/H5N1: genetic evolution and protective effi cacy of NIBRG-14 vacccine against the virus strains circulating in Vietnam

Dong Van Quyen

Institute of Biotechnology, Vietnam Academy of Science and Technology

Highly pathogenic avian H5N1 infl uenza viruses (H5N1 HPAI) is still posing a potential risk of causing outbreaks in poultry, with high frequency of annual endemics in Vietnam. In spite of HPAI H5N1 vaccination campaigns for domestic poultry, H5N1 viruses continue to circulate in Vietnam. This virus has frequently undergone reassortment to generate numerous multiple-order clades/subclades. Recent studies showed that three H5N1 HPAI clades were circulating in Vietnam including clade 2.3.2.1, clade 1.1 and re-emergence of clade 7.1/7.2. Clade 1.1, related to Cambodian strains, was predominant in the southern provinces, while clade 2.3.2.1 viruses were predominant in the northern and central provinces. The emergence of H5N1 HPAI viruses and the risk of a human pandemic have highlighted the need for advance stockpiling of vaccine. Current vaccines may be sub-optimally matched to the actual pandemic virus due to the rapid dissemination and ongoing evolution of avian H5N1 viruses. The WHO recently reported that the H5N1 poultry vaccine currently being used in Vietnam do not protect poultry against the new H5N1 clades (WHO, 2012b). Therefore, there is an urgent need for an in-depth understanding of factors that contribute to the virulence and resistance of these newly identifi ed infl uenza virus clades. In this report, we summarize evolutionary features of HPAI A/H5N1 viruses and clade formation during recent 10 years (2004-2014) in Vietnam. We also show here our data on evaluation on the NIBRG-14 vaccine immune effi ciency by challenging with the H5N1 virus clades circulating in Vietnam, and analyzing how the viruses can adapt and overcome its host cell immune response.

187 20-6

Capsular typing of Streptococcus pneumoniae clinical isolates in Bali

Ni Nengah Dwi Fatmawati1,2*, Ni Made Adi Tarini1, I Putu Bayu Mayura1

1Department of Clinical Microbiology, Medical School, Faculty of Medicine, Udayana University 2Molecular Biology Laboratory, Faculty of Medicine, Udayana University *[email protected]

As a part of the tropical area in Indonesia, Bali is prone to aid the spread of infectious diseases including respiratory tract infections. One of respiratory tract infectious agents is Streptococcus pneumoniae. This gram-positive bacterium can cause not only respiratory tract infections (pneumonia) but also more invasive infections such as sepsis and meningitis. One of S. pneumoniae major virulence factors is capsule. Polysaccharides capsule of S. pneumoniae are known as pneumococcal vaccine component. Among 90 capsule types of S. pneumoniae that have been investigated, several types have been found to be dominant in Indonesia such as types 6, 23, 15, 33 and 12 in West Nusa Tenggara, type 7F in Jakarta, and types 6A/B dan 15B/C in Central Java. However, almost no data has been reported in Bali about capsule genotype of S. pneumoniae. Therefore, the aim of this study was to determine capsule types of S. pneumoniae isolates in Clinical Microbiology Laboratory, Sanglah General Hospital, Denpasar, Bali. Twenty-one isolates that were isolated from blood (11/52.4%), sputum (5/23.8%), and other clinical specimens (5/23.8%) were included in this study. Identifi cation of S. pneumoniae was based on sensitivity of the isolates against optochin. All isolates were subjected to PCR for capsular typing. The result showed that 7 isolates (66.7%) were type 19F, 2 isolates (9.5%) were positive for 23F and also for type 6A/B. Furthermore, there was 1 isolate (4.8%) for each type 7F and 15B/C. Total 8 isolates (38.1%) were nontypeable isolates. This study showed the capsular types of S. pneumoniae clinical isolates in Bali, so far is quite unique if compared to those in other places in Indonesia. Further study now is still in progress to determine and characterize the nontypeable isolates.

Keywords: Streptococcus pneumoniae, capsular type, PCR, Pneumococcal vaccine

188 20-7

Analysis of Scd6 physiological activity through its interaction with Hmt1

Thi Kim Lien Pham , Kei Muroi, Yasuyuki Suda, and Kenji Irie

Graduate School of Comprehensive Human Science, University of Tsukuba

Messenger ribonucleoproteins (mRNPs) play essential roles in both translation initiation and mRNA stability. Actively translating mRNPs associate with polysomes to initiate translation whereas nontranslating mRNPs mostly assemble into processing-bodies (P-bodies) or stress granules (SGs). While P-bodies contain translationally inactive mRNAs and proteins involved in mRNA degradation machinery, SGs contain mRNAs and proteins stalled in translation initiation. Scd6, an RNA binding component of mRNPs, acts as a translational repressor and scd6∆ shows synthetic decapping defect with edc3∆. Here, we found that Scd6 associates with the protein arginine methyltransferase, Hmt1. Hmt1 is well-known as a mono- and asymmetric methyltransferase that catalyzes the methylation of arginine residues in several mRNA-binding proteins. Hmt1 binds to C-terminal 2RGG motifs in Scd6, methylates these regions and subsequently impairs the recruitment of Scd6 to cytoplasmic granules, P-bodies and SGs. Both hmt1∆ and scd6∆ show synthetic growth defects with dhh1∆ that implicates their overlapping functions relating to Dhh1. However, even though edc3∆scd6∆ shows synthetic growth defect, edc3∆hmt1∆ double mutant has similar phenotype as edc3∆ single mutant. Thus, our data imply that Hmt1 is required for the localization and activity of Scd6 which probably relates to Dhh1 activity.

189 20-8

Gene expression profi le of p53 apoptotic pathway genes in advanced breast cancer isolated from Indonesian patients after neo-adjuvant therapy

Syarifah Dewi1, Ramadhan Karsono2, Septelia Inawati Wanandi3

1Doctoral Programme of Biomedical Sciences, Faculty of Medicine, Universitas Indonesia 2Department of Oncology Surgery, Dharmais National Cancer Hospital 3Department of Biochemistry and Molecular Biology, Faculty of Medicine, Universitas Indonesia

Breast cancer is the second leading cause of cancer death in women worldwide. About 10% of new patients have been diagnosed at advanced stage. Treatment of advanced breast cancer remains palliative management, a combination of several modality including opera- tion, radiation, chemotherapy and hormonal therapy. Median survival time for patients with advanced breast cancer ranges between 24 and 30 months. Clinically, breast cancer is a heterogeneous disease. It is categorized based on molecular instrinsic expression, especially expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2). On the basis of these gene expression profi les, breast tumors are grouped into 3 major subtypes: luminal tumors (A and B) are characterized by high expression levels of hormonal receptors (ER and PR), HER-2-positive subtype is characterized by high expression levels of HER-2 and negative expression of ER and PR, and triple-negative tumors (or basal-like) show negative expression of HER-2, ER and PR and are described as the subtype with the worst prognosis. P53 is a tumor suppressor protein, a sequence-specifi c transcription factor, to induce cell growth arrest or apoptosis. p53 stimulates a wide network of signals that act through two major apoptotic pathways, extrinsic and intrinsic pathway. Inactivation of p53 leads to carcinogenesis process, therefore manipulation of p53 functions constitutes an attractive target for cancer therapy. This study investigate the gene expression profi le of p53 apoptotic pathway in advanced breast cancer after treatment and analyse the correlations with survival rate. Forty six breast cancer tissues from Indonesian patient was collected, before and after chemotherapy or hormonal therapy. Level of mRNA expression genes that related to p53 apoptotic pathway was measured by next generation sequencing (Miseq Illumina®), using p53 panel that consist of 52 genes. The survival rate of patient, subtype of breast cancer was evalu- ated and the correlation with alteration of genes expression was analyzed.

190 20-9

Novel Functional Domain in Human TMEPAI

Riezki Amalia, Yukihide Watanabe, Mitsuyasu Kato

Department of Experimental Pathology, Faculty of Medicine, University of Tsukuba

TMEPAI (Transmembrane prostate androgen-induced RNA) is a direct target gene of TGF-β signaling, antagonizes TGF-β signaling by interfering with TGF-β type I receptor (TβRI)-induced R-Smad phosphorylation. Structurally, TMEPAI consists of a transmembrane domain, two PY motif (PPxY), and a Smad-interacting motif (SIM). Kyoto Encyclopedia of Gene and Genome (KEGG) database was suggesting novel functional domain in human TMEPAI, a shisa-like motif. Original shisa protein physically interacts with immature form of the Wnt receptor Frizzled and FGF receptor within endoplasmic reticulum to inhibit their post translational maturation and traffi cking to the cell surface. Pei et al. (2012) reported shisa-like motif as the transmembrane adaptor. Predicted shisa-like motif in human TMEPAI consist about 70 amino acids, extends to the transmembrane domain and including some intracellular and extracellular domain amino acids. To confi rm TMEPAI function in Wnt signaling we performed luciferase assay. The result showed only membrane bound isoform of TMEPAI suppress Wnt signaling, and the TMEPAI family molecule, c18orf1 lacks this function. To understand and explore how this motif working in human TMEPAI we established the ab initio model using PHYRE2 and I-TASSER (Zhang Lab). We performed site-directed mutagenesis based on this predicted model, all mutation that leads to aromatic stacking interaction and secondary structure modifi cation slightly change the Wnt signaling suppression level. This data was suggesting shisa-like motif function as the transmembrane adaptors targeted membrane protein, but we need to do more experiment to understand how TMEPAI inhibits Wnt signaling and identify the target protein.

191 20-10

Drosophila duch knockdown as a potential model for studying Parkinson’s Disease pathogenesis and screening therapeutic antioxidants

Huynh Man Anh1, Tran Hoang Hiep1, Tran Linh Thuoc1,2, Dang Thi Phuong Thao1,2

1Department of Molecular and Environmental Biotechnology, University of Science, Vietnam National University Ho Chi Minh City 2Laboratory of Molecular Biotechnology, University of Science, Vietnam National University Ho Chi Minh City

SUMMARY Parkinson’s disease (PD) is a neurodegenerative disorder mainly characterized by impairment in locomotor behaviors and loss of dopaminergic (DA) neurons in the substantia nigra located in the midbrain. uch-l1 is a human gene which associated in PD pathogenesis. In fruit fl y Drosophila melanogaster, duch is the homolog of human uch-l1. Knockdown of duch in Drosophila brain also exhibited locomotor impairments and DA neuronal loss which imitates PD features. Increasingly, evidences from recent studies have suggested that oxidative damage contributes to the neuronal loss in PD. In addition, curcumin, an antioxidant derived from curry spice turmeric, could protect against PD which is demonstrated in several studies from various experimental models. In this study, Drosophila duch knockdown model was employed to study the effects of curcumin on PD features. The results showed that curcumin protect against the loss of DA neurons as well as the reduction in locomotor abilities. These results suggested that Drosophila duch knockdown model is a potential animal model to study PD pathogenesis and screening antioxidants for PD medication. Parkinson là bệnh thoái hoá thần kinh đặc trưng bởi sự suy giảm vận động và chết các tế bào sản sinh dopamine tại vùng chất đen của não giữa. uch-l1 là một gen của người liên quan đến sự phát sinh của bệnh Parkinson. Ở ruồi giấm, duch là gen tương đồng của uch-l1 ở người. Ruồi giấm bị knockdown gen duch ở não sẽ có những biểu hiện tương tự của bệnh nhân Parkinson như sự suy giảm vận động và chết của các tế bào thần kinh. Những dữ liệu từ các nghiên cứu gần đây cho thấy những tổn thương do oxi hoá góp phần gây ra sự chết tế bào ở bệnh Parkinson. Thêm vào đó, curcumin, một chất kháng oxi hoá được chiết xuất từ củ nghệ, có khả năng bảo vệ chống lại bệnh và điều này cũng đã được chứng minh bằng nhiều nghiên cứu trên các mô hình thí nghiệm khác nhau. Trong nghiên cứu này, mô hình ruồi giấm knockdown duch được sử dụng để nghiên cứu những tác động của curcumin trên những triệu chứng của bệnh Parkinson. Kết quả nghiên cứu cho thấy curcumin có khả năng bảo vệ chống lại sự thoái hoá của các tế bào thần kinh sinh dopamine cũng như sự thoái hoá của vận động. Những kết quả này gợi ý rằng ruồi giấm knockdown duch là một mô hình tiềm năng cho việc nghiên cứu cơ chế bệnh Parkinson và sàng lọc các chất kháng oxi hoá cho việc điều trị bệnh.

Keywords: Curcumin; dopaminergic neuron; Drosophila melanogaster; Parkinson’s disease; UCH-L1

 Author for correspondence: Tel: +84-8-38307079; E-mail: [email protected]

192 20-11

Mechanism of X chromosome reactivation during reprogramming

Bui Phuong Linh, Ken Nishimura, Aya Fukuda, Koji Hisatake

Laboratory of Gene Regulation, Faculty of Medicine, University of Tsukuba

Differentiated somatic cells can be reprogrammed into induced pluripotent stem (iPS) cells by overexpressing the four transcription factors, Oct4, Sox2, c-Myc and Klf4. However, the ineffi ciency of reprogramming and the low quality of iPS cells limit their potential applications in cell therapy. It is known that the female cells that have undergone X chromosome reactivation apparently have a high degree of pluripotency, suggesting a close functional relationship between acquisition of pluripotency and reactivation of an X chromosome. However, it remains unclear how the inactive X chromosome undergoes reactivation. To gain insight into X chromosome reactivation, we used 3S reprogramming system which generates intermediates of reprogramming (paused iPS cells). The system utilizes an SeVdp(fK-OSM) vector expressing Klf4 protein with a destabilization domain (DD), whose expression can be controlled by a small molecule, Shield1. We found that the 3S reprogramming system generates cells that have paused the X chromosome reactivation process at stages, which remain to be defi ned. To distinguish the gene expression from one allele of the loci on the X chromosome, we generated MEFs from Mus musculus (C57BL/6) and Mus spretus mice, which are evolutionarily distant and have one single nucleotide polymorphism (SNP) every 50 base pairs. Using these MEFs, we initiated to establish SNP genotyping by restriction enzyme digestion. In this system, the cDNA from X chromosome was amplifi ed by RT-PCR, followed by digestion by a restriction enzyme, whose recognition sequence overlaps with a SNP between Mus musculus (C57BL/6) and Mus spretus mice. We could successfully distinguish combinations of two alleles by digestion with restriction enzymes. In addition, we also utilized Taqman probes to establish SNP genotyping in a more quantitative manner. Our results show that the two alleles from Mus musculus (C57BL/6) and Mus spretus mice could be easily distinguished. In conclusion, the combined use of the 3S reprogramming system and SNP genotyping allows us to observe the reactivation of an inactive X chromosome and will provide detailed mechanisms of X chromosome reactivation during reprogramming.

193 NOTE

194 21 Student Presentations

Monday, September 28 - Wednesday, September 30 Venue: Conference Room 406 (Sept. 29-30) Lobby, Convention Hall 300 (Sept. 28-30)

Student Presentations

In this session, students of overseas par tner universities and the Universit y of Tsukuba give oral/poster presentations. This “Student Presentations” meeting has been held annually to advance research activities and facilitate international exchanges. Topics include medical science and life science.

Session Organizers: Shoko Saito, Hiroshi Hasegawa, Mamiko Sakata, Tadachika Koganezawa, Seiya Mizuno, and Yasuhiro Shinkai

Oral Presentations (Sept. 29, 9:00-17:00, Conference Room 406) 9:00-9:05 Opening Remarks Mitsuyasu Kato, University of Tsukuba Chairs: Masanori Sakaguchi, Yasuhiro Ishiga, Tran Thi Nhu Mai Part One University of Tsukuba Eszter Toth University of Tsukuba O-1 Single-cell nanobiopsy, a novel platform for the multiplexed analysis of 9:05-9:17 dendritic and axonal mRNA compartmentalization Kana Morohashi University of Tsukuba O-2 A high-throughput screening to discover inhibitors for insect steroidogenic 9:17-9:29 enzyme, Noppera-bo Eisuke Imura University of Tsukuba O-3 Identifi cation and characterization of novel neurons projecting to the steroid 9:29-9:41 hormone biosynthesis organ in Drosophila O-4 Naoki Toya University of Tsukuba 9:41-9:53 In vivo Ad-luc analyses of Leptin gene expression O-5 Takuya Kikuchi University of Tsukuba 9:53-10:05 Intestinal CREB3L3 prevents diet-induced hypercholesterolemia Wei-Min Chen National Taiwan University O-6 Sphingosine 1-phosphate potentiated endothelial cell attachment on de- 10:05-10:17 cellularized human umbilical vein as a scaffold for vascular tissue O-7 Ruoshi Li University of Tsukuba 10:17-10:29 The effect of sleep deprivation on the generalization of traumatic memories 10:29-10:45 Coffee Break Chairs: Koichiro Kako, Rie Wakimizu, Kouta Nizuma Part Two University of Tsukuba Jesavel A Iguchi University of Tsukuba O-8 RNA methylation stimulates recapping of messenger RNA in Trypanosoma 10:45-10:57 brucei O-9 Yuri Ushijima University of Tsukuba 10:57-11:09 A new role of nucleoid dynamics in Staphylococcus aureus

195 Emi Miwa University of Tsukuba O-10 The relationship between the genotypes and stroma formation of Epichloë 11:09-11:21 fungus inhabiting Brachypodium sylvaticum Keiko Yamaguchi University of Tsukuba O-11 The requisite support regarded by medical professions for children with 11:21-11:33 inherited metabolic disease and their families: a literature review Xerxes Seposo University of Tsukuba O-12 Temporal acclimation in temperature-mortality relationship using Excess Heat 11:33-11:45 Factor (EHF) Carolyn Kemunto University of Tsukuba O-13 Prevalence of anemia in infants 3-6 months in relation to breastfeeding 11:45-11:57 practices: A case of Mama Lucy Kibaki Hospital, Nairobi-Kenya 11:57-13:30 Lunch Break Part Three Chairs: Yuji Funakoshi, Zheng Ling, University of Tsukuba Fang Yu East China Normal University O-14 SUMO-modifi cation of CDK9 as a general mechanism for SUMO-mediated 13:30-13:42 transcriptional repression Wei-Chung Yu National Taiwan University O-15 Emerging roles for human topoisomerase III alpha in tumorigenesis 13:42-13:54 suppression via transcription regulation O-16 Dhouha Daassi University of Tsukuba 13:54-14:06 Functions of large Maf family transcription factors in Macrophages Yuji Fuse University of Tsukuba O-17 The heme-Bach1 axis determines the tissue specifi city of the Nrf2-dependent 14:06-14:18 heme oxygenase 1 induction Luong Cong Nho University of Tsukuba O-18 Interaction of 9,10-Phenanthraquinone-produced reactive oxygen species with 14:18-14:30 thioredoxin at a redox-active Cys32 and Cys35 14:30-14:45 Coffee Break Part Four Chairs: Ryusuke Niwa, Yu Ishikawa, University of Tsukuba Meng-Tsz Tsai University of Tsukuba O-19 The small GTPase Arf6 regulates the HGF-dependent cell proliferation 14:45-14:57 through PIP2-producing enzyme PIP5Kα in HepG2 cells Ngo Thai Bich Van University of Tsukuba O-20 Phospholipase D2 is a key molecule to suppress tumorigenesis through 14:57-15:09 activation of CD8+ T lymphocytes O-21 Tomokazu Kimura University of Tsukuba 15:09-15:21 GPNMB impacts to invasive properties of bladder cancer O-22 Shoko Nishizawa University of Tsukuba 15:21-15:33 BCL6 methylation in human peripheral T-cell lymphoma O-23 Seth Amin Figueroa University of California, Irvine 15:33-15:45 A spatial cell lineage model for healthy and diseased epithelial tissues 15:45-16:00 Coffee Break

196 Part Five Chairs: Michito Hamada, Taito Miyachi, University of Tsukuba Jorge Toledo University of Chile O-24 Structural dynamics of the endoplasmic reticulum mediated by cytoskeleton 16:00-16:12 modifi es luminal protein transport Mitsuaki Kashiwagi University of Tsukuba O-25 Identifi cation of a novel neuronal group that regulates REM-NREM sleep 16:12-16:24 switching Takato Honda University of Tsukuba O-26 Systematic behavioral screening of sleepy and dreamless, newly identifi ed 16:24-16:36 mouse pedigrees with sleep abnormalities Daiki Nakatsuka University of Tsukuba O-27 GABAergic neurons in the pontomedullary tegmentum control sleep and 16:36-16:48 wakefulness O-28 Brice de la Crompe University of Bordeaux 16:48-17:00 Optogenetic mapping of network dynamic in basal ganglia 2 min talk for Poster Presentations (Sept. 30, 9:00-10:35, Conference Room 406) P-1 National Taiwan University 9:00-9:02 P-2 National Taiwan University 9:02-9:04 P-3 National Taiwan University 9:04-9:06 P-4 National Taiwan University 9:06-9:08 P-5 National Taiwan University 9:08-9:10 P-6 National Taiwan University 9:10-9:12 P-7 National Taiwan University 9:12-9:14 P-8 National Taiwan University 9:14-9:16 Aya Takemura University of Tsukuba P-9 A part of Agr-defi cient ‘stealth’ Staphylococcus aureus can regain its virulence 9:16-9:18 during phagocytosis Moeko Minakuchi University of Tsukuba P-10 Prp18, a pre-mRNA processing factor 18, promotes infl uenza virus RNA 9:18-9:20 synthesis through NP chaperone activity Yohei Yamauchi University of Tsukuba P-11 The Arf6-specifi c GTPase-activating protein ARAP3 regulates breast cancer 9:20-9:22 cell invasion Yuki Tsunakawa University of Tsukuba P-12 MafB expressed in Osteoclast Precursors regulates osteoclastogenesis through 9:22-9:24 M-CSF signaling

197 P-13 K.M.G.M.K.K.Kulathunga University of Tsukuba 9:24-9:26 Novel imaging technique for atherosclerosis P-14 Yunshin Jung University of Tsukuba 9:26-9:28 Gene analysis of “Liver-Insulin Producing Cells” using MIP-GFP mouse Miki Shimbo University of Tsukuba P-15 Both chondroitin sulfate N-acetylgalactosaminyltransferase-1 and -2 are 9:28-9:30 necessary for endochondral ossifi cation P-16 Keigo Asano University of Tsukuba 9:30-9:32 MafB defi ciency impairs the apoptotic cell clearance of macrophages Tomoki Sakasai University of Tsukuba P-17 Establishment and application of ROSA26 Halo-iRFP fl ox Mice and non- 9:32-9:34 invasive fl uorescence imaging of disease-model mice Kosuke Kawamura University of Tsukuba P-18 Establishment of an analysis system utilizing protein degradation and near 9:34-9:36 infrared fl uorescent proteins P-19 Chen Chen University of Tsukuba 9:36-9:38 Roles of GPNMB in breast cancer stem cells 9:38-9:50 Coffee Break Christina-Sylvia Andrea University of Tsukuba P-20 Histone demethylase LSD1 is important for the endodermal organ development 9:50-9:52 in zebrafi sh P-21 Yoshikazu Hoshino University of Tsukuba 9:52-9:54 Simple generation of hairless mice by the CRISPR/Cas9 system P-22 Yuki Hirose University of Tsukuba 9:54-9:56 Hypnotic and teratogenic effects of thalidomide can be dissociated Hiromu Tominaga University of Tsukuba P-23 A novel, small-molecule orexin type 2 receptor agonist improves narcoleptic 9:56-9:58 symptoms in orexin-null mice Toshiya Yonezawa University of Tsukuba P-24 Orexin B exerts an indirect, slow inhibitory action on noradrenergic neurons 9:58-10:00 in the locus coeruleus Ryo Ishii University of Tsukuba P-25 Two-photon calcium imaging of the cerebral cortex in naturally sleeping and 10:00-10:02 awake mice P-26 Manami Kikuchi University of Tsukuba 10:02-10:04 The role of Elovl6 in bone and cartilage Hui Zhao University of Tsukuba P-27 Deletion of Elovl6 protects against the onset and progression of type 2 diabetes 10:04-10:06 in db/db mice P-28 Fusaka Oikawa University of Tsukuba 10:06-10:08 The role of CREBH in the small intestine Koichiro Maie University of Tsukuba P-29 Hereditary thrombocytosis with a germline mutation in the kinase domain of 10:08-10:10 JAK

198 P-30 Tatsuhiro Sakamoto University of Tsukuba 10:10-10:12 Notch signaling pathway of nestin-expressing cells in bone marrow Quang Le University of Tsukuba P-31 Ceramide/Ceramide-1-phosphate balance and the cisplatin-induced apoptosis 10:12-10:14 of cochlear hair cells P-32 Tomomi Okajima University of Tsukuba 10:14-10:16 Molecular basis of microglial properties regulated by culture condition Tomotsune Ameku University of Tsukuba P-33 Neuroendocrine control of mating-induced female germline stem cell 10:16-10:18 proliferation in the fruit fl y Drosophila melanogaster Chikana Yamamoto University of Tsukuba P-34 Glutathione biosynthesis is essential for larval development in the fruit fl y 10:18-10:20 Drosophila melanogaster Hitomi Takemata University of Tsukuba P-35 The effect of the parasitic wasp Asobara japonica on the development of its 10:20-10:22 host, the fruit fl y Drosophila melanogaster Drauna Adi Miriama Naioba Drauna University of Tsukuba P-36 Risk factor analysis of diabetes in Fiji; a comparison of the fi ndings from the 10:22-10:24 WHO STEPS survey in 2002 and 2011 P-37 Noriko Ozawa University of Tsukuba 10:24-10:26 Impact on the mother of the preparation to children receiving proton therapy P-38 Daichi Araki University of Tsukuba 10:26-10:28 Analysis of center-of-gravity variation on bed for fall prediction P-39 Chisato Yamazaki University of Tsukuba 10:28-10:30 Changes in Nursing Practice by Using Cognitive Behavioral Therapy Poster Exhibitions (Sept. 28-30, Lobby, Convention Hall 300) Discussion time (Sep 30, 10:50-12:00) Awards Ceremony (Sept. 30, 13:00-13:30, Conference Room 406) Closing Remarks Prof. Akira Shibuya

199 O-1

Single-cell nanobiopsy, a novel platform for the multiplexed analysis of dendritic and axonal mRNA compartmentalization

Eszter Toth1,2,3, Sol Katzman3, Wendy Lee3, Akshar Lohith3, Akiyoshi Fukamizu1,2, Nader Pourmand3

1Ph.D. Program in Human Biology, School of Integrative and Global Majors, University of Tsukuba 2Life Science Center, Tsukuba Advanced Research Alliance, Department of Life and Environmental Sciences, University of Tsukuba 3Depertment of Biomolecular Engineering, Jack Baskin School of Engineering, University of California at Santa Cruz

In highly polarized cell types, such as neurons, compartmentalization of mRNA and local protein synthesis may be implemented in fast, remarkably precise, local responses to external stimuli. mRNA transport is of high importance for growth cone guidance, maintenance, injury response, memory formation and nociception. Mutations affecting mRNA localization lead to devastating consequences, such as mental retardation or neurodegenerative diseases1. Comparative subcellular transcriptome analysis of neurons faces many technical burdens. In situ hybridization can provide high spatial resolution, but can detect very few genes at a time. Multiplexed methods—so far—require the bulk physical isolation of neuronal processes, therefore all information about mRNA spatial distribution was lost. In addition, previous studies used different cell types for axonal and dendritic transcriptome analysis, making data comparison very diffi cult. Previously, there was no available method for multiplexed, dendritic and axonal transcriptome analysis at the single-cell-level. Our group has recently developed a label-free, single-cell nanobiopsy platform based on scanning ion conductance microscopy (SICM), that uses electrowetting within a quartz nanopipette to extract cellular material from living cells with minimal disruption of the cellular milieu2. In this study—as a new approach to sample from neuronal processes—we used our nanobiopsy platform to extract samples from the soma, dendrites or axons of human Induced Pluripotent Cell-derived iCell® Neurons, and analyzed the multiplex mRNA pool with Next Generation RNA Sequencing. Due to the minute volume of a nanobiopsy sample, it is possible to extract samples from multiple locations in the same cell. In addition to the previously identifi ed transcripts, we report a new set of mRNAs that specifi cally localize to dendrite or axon. Hence, our single-neuron nanobiopsy study can deepen our understanding of compartmentalization of mRNAs, cellular circuitry, neuronal growth, maintenance and network formation.

1. Jung, H., Gkogkas, C. G., Sonenberg, N. & Holt, C. E. Remote control of gene function by local translation. Cell 157, 26–40 (2014). 2. Actis, P. et al. Compartmental genomics in living cells revealed by single-cell nanobiopsy. ACS Nano 8, 546–553 (2014).

200 O-2

A High-Throughput Screening to Discover Inhibitors for Insect Steroidogenic Enzyme, Noppera-bo

Kana Morohashi1 and Ryusuke Niwa1,2

1Graduate School of Life and Environmental Sciences, University of Tsukuba 2PRESTO, JST, Japan

In insects, developmental transitions such as molting and metamorphosis are triggered by the principal insect steroid hormone so-called ecdysteroid. Ecdysteroid is unique in a chemical structure and is largely different from steroid hormones of many organisms other than insects, including mammals. Thus, it is theoretically expected that a chemical agent that specifi cally inhibit ecdysteroid biosynthesis or ecdysteroid functions would be a useful and safe Insect Growth Regulator (IGR), a substance to control populations of harmful insect pests. Ecdysteroids are synthesized from dietary cholesterol via a series of hydroxylation and oxidation steps. One of those steps requires Noppera-bo, the insect-specifi c glutathione S-transferases (GSTs), essential for controlling the behavior of cholesterol in the ecdysteroid- biosynthesizing organ (Enya et al. Sci. Rep. 2014). Since recombinant GST proteins are effortlessly expressed and purifi ed using E. coli expression system, we have succeeded in obtaining a large amount of the purifi ed, soluble Noppera-bo proteins. Also, GST enzymatic activity is easily detected with artifi cial fl uorescent probes, which can be utilized for a high throughput screen to discover GST inhibitors. Therefore, we anticipate that Noppera-bo is the great target for developing a new IGR. We obtained recombinant Noppera-bo proteins from the fruit fl y Drosophila melanogaster, the malaria vector mosquito Anopheles gambiae, and the cabbage moth Plutella xylostella. We also purifi ed 2 other non-Noppera-bo type GSTs in D. melanogaster for control experiments. Using these recombinant proteins with the highly-sensitive artifi cial fl uorescent probe, 3, 4-DNADCF (Fujikawa et al. Chem. Comm. 2015), we developed and optimized a high throughput assay system. We applied this system to conduct the high throughput screen to fi nd out chemical compounds that inhibit Noppera-bo enzymatic activities using a chemical library containing 9,600 compounds. We got several candidate compounds that specifi cally inhibit the activity of Noppera-bo. Further results will be presented.

201 O-3

Identifi cation and characterization of novel neurons projecting to the steroid hormone biosynthesis organ in Drosophila

Eisuke Imura1, Yuko Shimada-Niwa2, Ryusuke Niwa1,3

1Graduate School of Life and Environmental Sciences, University of Tsukuba 2Life Science Center of Tsukuba Advanced Research Alliance, University of Tsukuba 3PRESTO, JST, Japan

Steroid hormones play key roles in many aspects of development, growth and reproduction in multicellular organisms. In insects, the principal steroid hormone ecdysteroid controls developmental transitions, represented by molting and metamorphosis. During the larval stages, ecdysteroid is biosynthesized in the specialized endocrine organ known as the prothoracic gland (PG). It is well known that ecdysteroid biosynthesis in the PG is affected by several environmental cues, such as photoperiod and nutrition. Thus, there must be essential regulatory mechanisms of ecdysteroid biosynthesis, especially the neuronal regulatory mechanism, in response to environmental cues. In the fruit fl y Drosophila melanogaster, so far PTTH neurons and SE0PG serotonergic neurons have been reported as the neurons projecting to the PG and regulating ecdysteroid biosynthesis [McBrayer et al. Dev. Cell 2007; Shimada-Niwa and Niwa. Nature Commun. 2014]. However, only these two types of neurons cannot account for the regulation of ecdysteroid biosynthesis in response to the complicated environmental stimuli. Given this situation, in this study, we aim to fi nd novel neurons projecting to the PG in D. melanogaster. Using the HHMI Janelia GAL4 strain collection, we attempted to fi nd and anatomically characterize neurons innervating the PG. Besides PTTH and SE0PG neurons, we identifi ed at least additional 2 types of neurons. In this presentation, the involvement of these novel neurons in ecdysteroid biosynthesis will also be discussed.

202 O-4

In vivo Ad-luc analyses of Leptin gene expression

Naoki Toya1,2, Naoya Yahagi1,2,3, Yoshinori Takeuchi1,2, Makiko Nishi1,2,3, Yoshikaz u Sawada1,2, Piao Xian Ying 1,2, Yuichi Aita1,2, Yukari Oya1,2, Akito Shikama1,2, Yukari Masuda 2,4, Midori Kubota2,4, Yoshihiko Izumida2,4,Takashi Matsuzaka1, Yoshimi Nakagawa1, Nobuhiro Yamada3, Takashi Kadowaki4, Hitoshi Shimano1

1Department of Internal Medicine, Faculty of Medicine, University of Tsukuba 2Nutrigenomics Research Group, Faculty of Medicine, University of Tsukuba 3Department of Internal Medicine, Graduate School of Medicine, University of Tokyo 4Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, University of Tokyo

[Background] Leptin is a hormone secreted from white adipose tissue which plays a key role in the regulation of appetite and energy consumption through the leptin receptor in hypothalamus. Leptin gene expression is specifi c to white adipose cells, and is increased in obesity. However, its regulatory mechanism is not clear. Our research group has established an intra-organ assay system that combines adenovirus-mediated transduction of luciferase reporter gene into liver or adipose tissue with in vivo imaging system (IVIS) technique (in vivo Ad-luc analytical system), and we have succeeded in identifying the important genome regions for the nutritional regulation around several genes in liver and adipose tissue. [Aim] We tried to identify the functional cis-elements around the leptin gene that are activated in differentiated or hypertrophied state of adipocytes through in vivo Ad-luc analyses. [Methods] First, we made the construct which contains -120bp 5’upstream of the leptin gene transcription start site (TSS) linked to the Luciferase reporter gene (-120bp-Lep promoter-luc). In order to investigate the entire 72kbp genome region between the two CTCF binding sites that surrounds the leptin gene, it was cloned as 18 pieces of DNA fragments of 4kbp length, and then each DNA fragment was inserted into the 5’ side of -120bp- Lep promoter-luc vector. The injection method of adenoviruses into adipose tissue using microsyringe was previously established in our laboratory. [Results] We observed the important genome region to up-regulate leptin gene expression with obesity level by using in vivo Ad-luc analyses. Furthermore, we found some transcription factors that bind to that region by using TFEL scan. Now we are searching in more detail the region for the functional cis-elements involved in the regulation of leptin gene expression in the obesity models and cultured adipocytes.

203 O-5

Intestinal CREB3L3 prevents diet-induced hypercholesterolemia

Takuya Kikuchi1,2, Yoshimi Nakagawa2, Kana Orihara2, Fusaka Oikawa2, Aoi Sato2, Yoshinori Oosaki 2, Han SI2, Yoshinori Takeuchi2, Kiyoaki Ishii2, Takashi Matsuzaka2, Naoya Yahagi2 and Hitoshi Shimano1,2

1School of Integrative and Global Majors, University of Tsukuba 2Department of Internal Medicine, Metabolism and Endocrinology, Faculty of Medicine, University of Tsukuba

CREB3L3, cyclic AMP-responsive element-binding protein 3-like 3, is a liver and intestine- specifi c transcription factor localized in the ER membrane. CREB3L3 is activated by ER stress, infl ammatory stimuli, and metabolic signals in the liver. The activation of CREB3L3 is through intramembrane proteolysis mediated by Golgi-resident site-1 and site-2 proteases, the same enzymes responsible for the cleavage of sterol response element-binding proteins (SREBPs), the regulators of lipid biosynthesis. Previously, it has been shown that global depletion of CREB3L3 leads to hypertriglyceridemia via modulation of the expression of hepatic genes involved in lipolysis, de novo lipogenesis, as well as fatty acid elongation and oxidation. In this study, we investigated the role of intestinal CREB3L3. We developed PEPCK promoter driven-CREB3L3 transgenic (CREB3L3 Tg) mice, which express the transgene highly in duodenum, jejunum, ileum, colon, white adipose tissue, brown adipose tissue and muscle. Microarray data of the intestine of CREB3L3 Tg mice showed that CREB3L3 overexpression decreased genes related to cholesterol absorption in the intestine. Endogenous intestinal Creb3l3 mRNA expression was highest in the proximal part of intestine, where cholesterol is absorbed. To examine the effect of CREB3L3 on cholesterol metabolism, CREB3L3 Tg mice were fed a high cholesterol diet (HCD) for 2 weeks. Plasma cholesterol, hepatic lipid accumulation, and cholesterol crystal formation in the gallbladder were decreased in CREB3L3 Tg mice compared to the control mice. CREB3L3 Tg mice showed reduced expression of genes related to cholesterol metabolism and transport in the intestine, such as Lxrβ, Abca1 and Abcg5/8. Of note, CREB3L3 Tg mice had the reduced expression of Niemann-Pick C1- Like 1 (Npc1l1), which is localized in jejunal enterocytes and critical for intestinal cholesterol absorption. Taken together, these results indicate that CREB3L3 could attenuate diet-induced hypercholesterolemia, which has important implications in the understanding and treatment for hypercholesterolemia and its related disease.

204 O-6

Sphingosine 1-phosphate Potentiated Endothelial Cell Attachment on De-cellularized Human Umbilical Vein as a Scaffold for Vascular Tissue

Wei-Min Chen1, Kai Hsia2, Chao-Ling Yao3, Jen-Her Lu2, Hsinyu Lee1

1National Taiwan University 2Taiwan Taipei veterans General Hospital 3Yuan Ze University

Cardiovascular disease (CVD) is the leading cause of mortality and morbidity. Choosing a proper material for bypass grafting and avoiding postoperative coagulopathy is critical. In this study, human umbilical veins (HUV) was applied as natural allograft scaffolds and de- cellularized to remove antigens from HUV donor. De-cellularized scaffold was then seeded with human umbilical vein endothelial cells (HUVECs) or endothelial progenitor cells (EPCs) in the presence of sphingosine 1-phosphate (S1P) in rotational cultural conditions. Previous study shows that S1P is a key biolipid signaling molecular that regulates endothelial cell growth and survival. S1P was hypothesized to enhance cells re-attachment onto scaffold and stabilize the surface glycocalyx layer of endothelial cell, which inhibit blood coagulation. Adhesion assays and H&E stain of scaffold section showed S1P indeed enhanced cell adhesion on scaffold. Further, Immunofl uorescence and SEM (Scanning Electron microscope) results showed S1P prevented syndecan-1 shedding but not glypican-1. Furthermore, S1P enhanced scaffold reduced platelet adhesion in whole-blood coagulation tests. The identifi cation of a mechanism that account for inhibition of coagulation due to protection from glycocalyx shedding by S1P indicated that S1P enhanced re-cellularized HUV scaffolds are potentially suitable for vascular grafts.

205 O-7

The Effect of Sleep Deprivation on the Generalization of Traumatic Memories

Ruoshi Li1, Ayano Fujinaka1, Masanobu Hayashi1, Deependra Kumar1, Keisuke Naito1, Kousuke Miki1, Taihei Nishiyama1, Michael Lazarus1, Takeshi Sakurai1,2, Nohjin Kee3, Satomi Nakajima4, Szu-Han Wang5, Masanori Sakaguchi1

1International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba 2Department of Molecular Neuroscience and Integrative Physiology, Faculty of Medicine Kanazawa University 3University of Toronto 4Department of Adult Mental Health, National Center of Neurology and Psychiatry, National Institute of Mental Health 5Centre for Clinical Brain Sciences, University of Edinburgh

Memory generalization is a major cause of distress for patients suffering from post- traumatic stress disorder (PTSD). PTSD patients often confuse traumatic memories with familiar but harmless memories. Due to this inability to discriminate between traumatic and normal memories, PTSD patients experience symptoms, such as fl ashbacks and panic attacks. Therefore, understanding the mechanism of memory generalization would lead to the development of new ways to treat PTSD. It has been discovered in previous experiments that when mice are exposed to a familiar context (context B) within 24 hours of traumatic experience (electric foot shock) in a specifi c context (context A), the mice would confuse the familiar but harmless context with the traumatic context. We think that sleep plays an important role in this phenomenon. Here, we decided to evaluate the effect of sleep on the generalization of memory. Mice were given electric foot shock in context A and then exposed to context B 6 hours later. They were sleep deprived right after the exposures. When their freezing levels in context A and context B were tested the next day, they showed high level of freezing in context A, but signifi cantly low level of freezing in context B. This fi nding could contribute to the better understanding of the mechanism of memory generalization. It could also present a possible treatment for patients with PTSD. Reference: Fujinaka A, Hayashi M, Li R, Kumar D, Naito K, Miki K, Nishiyama T, Lazarus M, Sakurai S, Kee N, Nakajima S, Wang SH, Sakaguchi M, Acute effect of context exposure after trauma on memory generalization, under review

206 O-8

RNA methylation stimulates recapping of messenger RNA in Trypanosoma brucei

Jesavel A Iguchi, Anna V Ignatochkina and C. Kiong Ho

Department of Infection Biology, Graduate School of Comprehensive Human Sciences, University of Tsukuba

Trypanosoma brucei is a kinetoplastid protozoan parasite that causes African sleeping sickness in humans and Nagana in domestic animals. Virtually all kinetoplastid mRNA possess cap 4 structure (m7Gpppm6,2AmpAmpCmpm3Um) on the mature mRNA, which consists of standard cap 0 (m7Gppp-) with additional methylations at seven sites within the fi rst four transcribed nucleosides. Trypanosoma brucei encodes a cytoplasmic recapping enzyme, TbCe1, which converts decapped monophosphorylated RNA into an unmethylated capped (GpppN-) RNA. However, in order to generate a translatable mRNA by TbCe1, the cap must be further methylated at (guanine N-7) position to form m7GpppN. We hypothesize that TbCmt1, which was previously shown to function as (guanine N-7) RNA methyltransferase, act together with TbCe1 in the cytoplasmic mRNA recapping pathway. We expressed the Protein C-TEV- Protein A tag (PTP)-TbCmt1 fusion protein and showed that TbCmt1 is likely localized in the cytoplasm. We further demonstrated that TbCmt1 methyltransferase activity was stimulated by hypermethylation found in cap 4 structure. These results imply that TbCmt1 functions together with TbCe1 in the mRNA recapping pathway and suggests that mRNA recapping is selectively regulated by differential cap methylation. TbCmt1 may also act as a surveillance enzyme to ensure that only the hypermethylated capped RNAs return to the translational pool.

207 O-9

A new role of nucleoid dynamics in Staphylococcus aureus

Yuri Ushijima1, Ryosuke L. Ohniwa2,3, Shinji Saito2, Kazuya Morikawa2

1Graduate School of Comprehensive Human Science, University of Tsukuba 2Faculty of Medicine, University of Tsukuba 3Center for Biotechnology, National Taiwan University

Bacterial genome is packed in a cell as a form of nucleoid with hundreds of proteins and RNAs. The nucleoid consists of fi ber structures ranging from 10 nm ~ 80 nm. These fi bers are commonly observed in a broad range of bacteria grown in optimal conditions. However, in some bacterial species under stress conditions, the nucleoid undergoes a dynamic struc- tural change, e.g. nucleoid is compacted in a stepwise manner towards stationary phase in Escherichia coli, while nucleoid of Staphylococcus aureus is clogged in response to oxidative stresses. In either case, Dps family proteins (Dps in E. coli, and MrgA in S. aureus) serve as the nucleoid compaction/clogging factor. S. aureus is an opportunistic human pathogen and has to cope with a series of host bacteri- cidal factors including oxidative stress in phagosomes. The oxidative stress is directly sensed by a transcription factor, PerR, that regulates the expression of MrgA. MrgA has DNA binding activity and clogs the nucleoid. In addition, MrgA has ferroxidase activity that contributes to the oxidative stress resistance by preventing hydroxyl radical formation via Fenton reaction. We previously showed that the deletion of the mrgA gene has pleiotropic effect: 1) inability to clog nucleoid, 2) high susceptibility to the oxidative stress and UV irradiation, 3) reduced sur- vival in the presence of macrophages. However, the exact role of the nucleoid clogging in the survival against macrophages is elusive. Here, we present a series of data indicating that the nucleoid clogging is not suffi cient for oxidative stress resistance, while the ferroxidase activ- ity of MrgA is essential. Instead, we discovered that the nucleoid clogging affects expression of about 100 genes, many of which are not directly related to oxidative stress tolerance. The role of nucleoid clogging as a new regulatory mechanism of gene expression will be discussed regarding the infection processes of S. aureus.

208 O-10

The relationship between the genotypes and stroma formation of Epichloë fungus inhabiting Brachypodium sylvaticum

Emi Miwa, Izumi Okane, Yuichi Yamaoka

Faculty of Life and Environmental Sciences, University of Tsukuba

Fungi belonging to the genus Epichloë (Clavicipitaceae, Ascomycota) are symbionts of many grasses. In sexual cycle, they produce external stroma and spread by ascospores, whereas, in asexual cycle, fungi remain asymptomatic and transmit vertically via seeds. Although the differences of a mode of reproduction might be caused by the genetic characteristic of Epichloë fungi, little is known about that of wild grasses. The purpose of this study is to investigate the genetic diversity of an Epichloë fungus inhabiting Brachypodium sylvaticum and reveal the symbiotic lifestyle of the fungus on its host plants. We placed two experimental plots at Kawakami forest of University of Tsukuba in Nagano Prefecture, Japan. 80 plant individuals growing in the two plots were tagged, and checked the stroma formation from June to October in 2014. At the same time, we collected tillers from the 80 plants to isolate the Epichloё fungus. Sequencing of rDNA ITS and β-tubulin gene regions of these isolates were conducted to detect genetic polymorphism. 77 isolates from 68 of 80 plants individuals were obtained. Analysis of combined sequences of rDNA ITS and β-tubulin gene regions revealed 6 fungal genotypes (hereafter, ‘groups I~VI’) in B. sylvaticum growing in Kawakami forest. Group I (isolate no: 37) was most predominant and isolated from both stroma-forming plants and asymptomatic plants. The stroma formation was observed on all of the plants from which groups II (3) and III (3) were isolated and in contrast, that was hardly observed on the plants from which groups IV (6), V (14) and VI (14) were isolated. Analysis of mating-type genes showed that group III, V and VI was composed of only isolates having one kind of idiomorph, that is, MTB (mtBA). This study showed that the stroma formation, or Epichloë-host relations, were likely to depend on the genotypes of the Epichloë fungus. Namely, groups I~III maintain the relations by both horizontal spread and vertical transmission, and groups IV~VI almost lack the possibility of horizontal spread and maintain the mutualistic relations only by vertical transmission via seeds.

209 O-11

The requisite support regarded by medical professions for children with inherited metabolic disease and their families : a literature review

Keiko Yamaguchi1, Rie Wakimizu2

1Master’s program in Nursing Science, the Graduate school of Comprehensive Human Science, University of Tsukuba 2Department of Child Health Care Nursing, Division of Health Innovation and Nursing, Faculty of Medicine, University of Tsukuba

There are about 19,000 patients with an inborn metabolic disease (IMD) in Japan in 2013. Many researchers conducted the research on the diagnosis and treatment. With expanding the tandem mass newborn screening, there are several researches on their living condition and QoL. However, there are only few researches mentioned the subjective support needs of pa- tients and their families and the requisite support regarded by medical professions. To consider the suggestion for improving their QoL, we conducted the literature review focused on the support that the medical profession regarded as requiring for the patients with IMD and their families. We used the two search engines online : Japan Medical Abstracts Society version 5 and Pubmed. We fi nally targeted 11 literatures written in Japanese. Medical professions regarded it’s necessary to provide an education of diet therapy to the children with IMD themselves from childhood for a good health control. And the patients need to be able to care themselves as the patients with chronic disease. The researchers suggested that the team medical care is important, and they should make a model of a self-care behav- ior for patients with IEM, for fulfi llment of team medical care. Also according to a previous study, an education of self-care should be provided with putting their hands together as con- sidering their growth and development, intelligibility, concept of value, and prizing them. At the same time, it’s important to structure the support system for the child with IMD and their families in Japan. For the fi rst step, the quantitative and qualitative studies of their QoL and subjective support needs should be researched comprehensively.

210 O-12

Temporal Acclimation in Temperature-Mortality Relationship using Excess Heat Factor (EHF)

Xerxes Seposo1, Tran Ngoc Dang1,3, and Yasushi Honda2

1Graduate School of Comprehensive Human Sciences, University of Tsukuba 2Department of Environmental Health, Faculty of Public Health, University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam 3Faculty of Health and Sports Sciences, University of Tsukuba

Numerous studies have already proven that heat stress due to heat wave days (HWD) increase the risk of dying especially in unusually hot days. Heatwave (HW) defi nitions vary per region in the world. One of the most common quantifi cations of HW is the use of “duration” and “intensity”. In certain occasions during HWDs, mortality displacement occurs, whereby heat-related excess mortality is followed by mortality defi cit. This happens when the high relative risks (RR) in the initial days are followed by low RRs in the succeeding days. In some instance, the risk spikes up again which leads to the notion of temporal thermal acclimation. This study explores the plausibility of temporal acclimation in the temperature-mortality relationship using a novel heat index, excess heat factor (EHF) which takes into account the personal temporal acclimation.

We gathered the meteorological and all-cause mortality variables from the respective agencies in the Philippines from 2006-2010 and modeled the fi rst stage analysis via distributed lag nonlinear model (dlnm) using the Manila City variables. Durations (>2, >5, >7) and intensities (95th, 97th, 99th) used for HWD defi nitions were all based from literature. All statistical techniques were carried out with R Programming. Results showed that EHF can also be as good as the usual HWD defi nitions. Adding the acclimation variable, signifi cant at p-value<0.05, with the usual HWD defi nitions creates a better model having the lowest Akaike Information Criteria (AIC) value of 12696.21. In modeling the temporal relationship of temperature-mortality, there is a need to take into account the possible personal acclimation so as to have a better picture of the heat effects in temporal scale. The study is limited to the gathered data and was not able to take into account the biological/physiological acclimation and usage of fans/air-conditioners due to data unavailability.

211 O-13

Prevalence of Anemia in Infants 3-6 Months in Relation to Breastfeeding Practices: A Case of Mama Lucy Kibaki Hospital, Nairobi-Kenya

Carolyn Kemunto1, Yukiko Wagatsuma1, Jasper K Imungi2, Wambui Kogi-Makau2

1Department of Clinical Trial and Clinical Epidemiology, University of Tsukuba 2Food Science Nutrition and Technology, University of Nairobi

Anemia in infancy is associated with a range of important developmental and clinical issues. Although studies have been carried out on breastfeeding and supplementary feeding of infants, so far, little information exist on the relationship between breastfeeding practices and the development of anemia in infants. This study was therefore designed to assess the association between breastfeeding type, maternal iron status and other associated factors on hemoglobin concentration in the blood of 3-6 months old infants. The study was cross sectional survey involving both descriptive and analytical study design. A previously pretested structured questionnaire was administered to collect socio- demographics and socio-economic characteristics of the household, infant feeding practices, morbidity, nutritional status, hemoglobin levels and anthropometry of the mothers. Blood for hemoglobin analysis was drawn by qualifi ed and trained technician. Results were analyzed using Chi-square to determine the difference between proportions, logistic regression and bivariate correlation to establish relationships and odds ratio to estimate the relative risk. The statistical analyses were carried out using the Statistical Package for the Social Sciences (SPSS), version 12. In total, 250 mother infant dyads participated in the study. Majority (91.5%) of the respondents were aged 20-35, years while only 4.5% were 19 years and below. Among the infants studied, 52% were males and 48% were females. The greatest share of the infants was aged 5 months (38%). The mean age of the infants was 4.12 ranging from 3-5.98 months. Most of the infants (57.0%) were exclusively breastfed. The rates of under nutrition were low with wasting at 1.2%, underweight at 2.0% and stunting at 11.25%. Up to 96.3% of the infants had been immunized completely for their age at three months. The mean prevalence of anemia in the infants was 54.5%, with 32.5% mild 22.5% moderate and 0.5% severe. Anemia in exclusively breastfed infants was 31% compared to 23.5% in the non-exclusively breastfed. The mean hemoglobin level was 10.7 g/dL. Low birth weight (P=0.029), maternal iron supplementation during pregnancy (P=0.023), infant sickness in the preceding two weeks prior to the survey (P=0.02) and breastfeeding practices (OR=1·46; 95%=1.3, 2.6, P<0·05) were signifi cantly associated with anemia in infants. The study suggested that exclusively breastfed infants are at risk of developing anemia (as compared to those who are introduced to complementary feeds earlier than six months). Therefore effective control strategies should be designed to address anemia in infants.

212 O-14

SUMO-modifi cation of CDK9 as a general mechanism for SUMO-mediated transcriptional repression

Fang Yu1, Guang Shi1, Shimeng Cheng1, Xianxin Du1, Jinke Cheng2, Jiwen Li1 and Jiemin Wong1*

1The institute of Biomedical Sciences and School of Life Sciences, Shanghai Key Laboratory for Regulatory Biology, East China Normal University 2Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Infl ammation, Shanghai Jiao Tong University School of Medicine

SUMO modifi cation has long been shown to correlate broadly with transcriptional repres- sion. Previous mechanistic studies have linked SUMO-mediated transcriptional repression to the recruitment and/or activation of histone deacetylase activities. Here we present evi- dence for SUMO-modifi cation of CDK9, a catylatic subunit of transcriptional elongation factor pTEFb, as a general mechanism for SUMO-induced transcriptional repression. CDK9 can be SUMO-modifi ed by multiple PIAS family proteins both in vivo and in vitro and SUMOylation of CDK9 inhibits the interaction between CDK9 and CyclinT1 and thus the formation of pTEFb complex. Overexpression of PIAS1 and SUMO1 in HeLa or HEK293T cells leads to substantially increased SUMOylation of endogenous CDK9 but not HDAC1. Importantly, the increased CDK9 SUMOylation correlates with decreased association between CDK9 and cyclinT1, decreased RNA polymerase II CTD Ser2 phosphorylation , and inhibition of global transcription. On the other hand, knockdown of Ubc9, the only identifi ed SUMO E2 conjuga- tion enzyme, leads to increased levels of RNA polymerase II CTD Ser2 phosphorylation and global transcription. Furthermore, an increased CDK9 SUMOylation and decreased global transcription were observed by western blot analysis of the protein extracts of MEF cells de- rived from either SUMO-specifi c protease 1 (SENP1) or SUMO-specifi c protease 2(SENP2) knockout mice, suggesting that CDK9 is under the dynamic regulation of SUMOylation and de-SUMOylation. We also observed that c-MYC, a general activator for transcriptional elon- gation, antagonizes CDK9 SUMOylation. Together our data point to SUMOylation of CDK9 as a general mechanism underlying SUMO-mediated transcriptional repression.

213 O-15

Emerging roles for human topoisomerase III alpha in tumorigenesis suppression via transcription regulation

Wei-Chung Yu1, Mei-Yi Hsieh1, Wan-Jung Lai1, Yen-Hsiu Yeh1, Tang-Long Shen2,3 and Tsai-Kun Li1,3

1Department and Graduate Institute of Microbiology, College of Medicine, 2Department of Plant Pathology and Microbiology, College of Bioresources and Agriculture, and 3Center for Biotechnology, National Taiwan University

Human DNA topoisomerase III alpha (hTop3α), via solving topological restraints generat- ed during DNA metabolism (e.g. transcription), contributes to different physiological functions including embryogenesis, DNA-repair surveillance and cell-cycle checkpoints. Previously, our study showed that hTop3α can bind to p21 promoter, and served as a chromatin co-regu- lator with p53 to regulate gene expression of p21 and thus involving in transcription program- ming of tumor suppression. This suggests a novel notion and provides the fi rst example of how a chromatin factor specifi cally involved in regulated gene expression. Moreover, using the zebrafi sh model, we found that zTop3α, through interacting with SMAD transcription fac- tors, affects ventral-dorsal development, further supporting our above notion. Here, in order to further understand hTop3α’s role(s) in the p53-dependent and -independent transcription programming of tumor suppression, we have carried out a comparative microarray analysis to seek for hTop3α- and/or p53-dependent gene expression in mediating tumorigenesis. Our results showed that gene expression of transcription factor SMAD4, which is involved in the BMP signaling pathway, is hTop3α-dependent. In addition, the expressing profi ling of MAPK signaling pathway has shown the highest correlation with the hTop3α level. Interestingly, chromatin factor histone deacetyltransferase 4 (HDAC4) has also shown some links with p53 and hTop3α. Ectopic expression of HDAC4 in HCT116 cells conferred a mobility-shifted band of Top3α, which is later demonstrated to be a phosphorylated form of hTop3α. Moreover, overexpressed HDAC4 also contributes to the downregulation of p53 regulated protein, p21, indicating the involvement of hTop3α-HDAC4 interaction in tumor suppression. Yet, the detail functional roles of and kinase(s) responsible for phosphorylated hTop3α remained to be deter- mined. In sum, our results reveals an emerging role for hTOP3α in development and tumor suppression via transcription regulation.

214 O-16

Functions of Large Maf Family transcription factors in Macrophages

Dhouha Daassi1,2, Michito Hamada, Mai Thi Nhu Tran, Satoru Takahashi

1Department of anatomy and embryology, Faculty of medicine, University of Tsukuba 2Laboratory Animal Resource Center, Division of Biomedical Science, Faculty of Medicine, University of Tsukuba

Background Phagocytes were named after the Greek “phago”: devour and “cytes”: cells into “macrophages” which refers to large eaters. New light has been shed on subtypes and polarization of macrophages. The polarized macrophages are named M1; classically activated (by IFNγ alone or with microbial stimuli (LPS) or cytokines (TNF and GM-CSF)) and M2; alternatively activated (by IL-4 or IL-13, immune complexes, IL-10 glucocorticoid or vitamin D3 hormones) (Mantovati et al., 2004). The molecular mechanism behind that remains unknown. The transcription factor MafB and another large Maf factor; c-Maf double defi cient mice showed endless self-renewal of macrophage potential in the presence of macrophage colony stimulating factor (M-CSF) (Aziz et al 2009). This suggests that they have overlapping functions in macrophages. However recent works show that they also present different functions. c-Maf is important for macrophage supporting hematopoiesis (Kusakabe et al 2011). MafB is important for atherosclerosis progress inhibition by macrophage apoptosis (Hamada et al 2014). Aim The Aim of this study is to check expression of MafB and c-Maf in various macrophage types to help understanding their functions. Results We studied MafB and c-Maf expression by Q-PCR and western blot analysis of wild type mice bone marrow macrophages stimulated by LPS, GM-CSF, IL-10 and IL-4 with IL-13. We also checked green fl uorescent protein (GFP) expression using Mafb/GFP knock-in mutant mice by FACS analysis. Our data showed that M2 macrophages highly expressed Maf B (more signifi cantly) and c-Maf but not M1. The latter result was supported by western blot analysis showing that MafB and c-Maf proteins were suppressed in M1. In addition, histological analyses showed MafB and c-Maf were similarly expressed in lymph nodes and skin macrophages and that only MafB is expressed in spleen.

Conclusion Our results indicate MafB and c-Maf have different expression pattern, which might explain functions they have in common and unevenly.

References [1] A. Mantovati, Trends in Immunology, Vol. 25, 677-686 (2004) [2] A. Aziz, Science, Vol. 326, 867-871 (2009) [3] M. Kusakabe, blood, Vol. 118, 1374-1385 (2011) [4] M. Hamada, Nature communications, Vol. 5, 10 (2014)

215 O-17

The heme-Bach1 axis determines the tissue specifi city of the Nrf2-dependent heme oxygenase 1 induction

Yuji Fuse, Hitomi Nakajima, Yaeko Nakajima-Takagi, Makoto Kobayashi

Faculty of Medicine, University of Tsukuba

Oxidative stress is an emerging topic in the recent medical research, since it is involved in a variety of diseases. One of the biological machinery to cope with oxidative stress is the Nrf2 system, which activates transcription of a broad spectrum of antioxidant genes including heme oxygenase 1. The induction profi le of this gene after Nrf2 activation has been investigated in zebrafi sh, which has an advantage in analyzing whole-body gene expression. Unlike other Nrf2 target genes in zebrafi sh, the induction of hmox1a, a zebrafi sh homolog of mammalian heme oxygenase 1, was liver specifi c (Nakajima et al. 2011 PLoS ONE). We focused on this unique expression pattern of hmox1a, aiming to elucidate one of the diverse stress response mechanisms of the Nrf2 system. We fi rst hypothesized that a repressive factor inhibits hmox1a induction in non-liver tissues. Among tested candidates, Bach1b inhibited the Nrf2-dependent induction of hmox1a, but not other target genes, fulfi lling the requirement as the hypothetical repressor. Knockdown analysis of bach1b and its teleost co-ortholog, bach1a, showed that both Bach1 are fundamental factors in the repression of hmox1a in non-liver tissues. The expression of both Bach1 genes turned out to be ubiquitous, which led us to hypothesize that the repressive activity of Bach1 is inhibited in the liver. As it is known that heme inhibits Bach1 function and the liver is presumed to be a heme-rich tissue, it is likely that heme is the liver-specifi c regulator of Bach1. To test this, we altered the heme level pharmacologically and showed that hmox1a was induced only in the tissue with high level of heme. From these experiments, we revealed that hmox1a is induced only when two conditions are achieved within a tissue: 1) Nrf2 activation and 2) Bach1 inhibition by heme. The physiological signifi cance of this dual regulation is that, in tissues with high heme level, oxidative stress is reduced by the induced hmox1a, while in low- heme-level tissues, the basal level of heme is retained by hmox1a repression. (Fuse et al. 2015 Genes Cells)

216 O-18

Interaction of 9,10-Phenanthraquinone-produced reactive oxygen species with thioredoxin at a redox-active Cys32 and Cys35

Luong Cong Nho1, Yumi Abiko1,2, Keiko Taguchi3, Yoshito Kumagai1,2

1Graduate School of Comprehensive Human Sciences, University of Tsukuba 2Faculty of Medicine, University of Tsukuba 3Department of Medical Biochemistry, Tohoku University Graduate School of Medicine

9,10-Phenanthraquinone (9,10-PQ), a major component in airborne particulate matter

(PM2.5), is an effi cient electron acceptor that readily reacts with dithiol compounds and protein proximal thiols, resulting in oxidation of the thiol groups and concomitant generation of reactive oxygen species (ROS). Meanwhile, thioredoxin (Trx), a key antioxidant protein containing a conserved –CXXC– active site motif, can play a role as electron donor to a large range of enzymes involving DNA synthesis and defense against oxidative stress through its disulfi de reductase activity regulating protein dithiol/disulfi de balance. In the present study, we explored whether or not 9,10-PQ could interact with Trx at a redox-active Cys32 and Cys35, thereby affecting its catalytic activity and thiol status in the body. Intratracheal injection of 9,10-PQ to mice caused reduction of pulmonary protein thiol content and diminished Trx activity in the lung in a concentration-dependent manner. With purifi ed wild Trx and its double mutant (32S and 35S mutant of Trx), we found that the Cys32 and Cys35 selectively serves as electron donor for 9,10-PQ, leading to substantial hydrogen peroxide production. Interestingly, dithiothreitol, but not GSH, inhibited reduction of Trx activity caused by 9,10-PQ. Exposure of 9,10-PQ to cells caused intracellular ROS generation, resulting in increasing of protein carbonyl formation and apoptotic cell death. However, overexpression of Trx in HepG2 cells blocked 9,10-PQ-mediated activation of p38, oxidation of protein and DNA fragmentation. These results suggest that Trx is one of a molecular target for 9,10-PQ through redox cycling of the quinone with Trx Cys32 and Cys35. We speculate that cellular reductants with a high antioxidant activity seem to protect Trx from 9,10-PQ.

217 O-19

The small GTPase Arf6 regulates the HGF-dependent cell proliferation through PIP2-producing enzyme PIP5Kα in HepG2 cells

Meng-Tsz Tsai1, Yuji Funakoshi1, Shih-Torng Ding2, Yasunori Kanaho1

1Department of Physiological Chemistry, Faculty of Medicine and Graduation School of Comprehensive Human Science, University of Tsukuba 2Depatment of Animal Science and Technology, National Taiwan University

The small GTPase ADP-ribosylation factor 6 (Arf6) plays critical roles in a wide variety of cellular events, including phosphoinositide metabolism, actin cytoskeleton reorganization and membrane recycling. We have previously demonstrated that Arf6-knockout mice are embryonic lethal with severe defect in liver development due to the impairment of HGF-dependent cord formation, suggesting that Arf6 plays a crucial role in the HGF signaling pathway in hepatocytes. However, the molecular mechanism by which Arf6 regulates HGF signaling in hepatocytes has not yet been clarifi ed. Here, we demonstrate that Arf6 is involved in the HGF-induced cell proliferation through activation of the phosphatidylinositol 4,5-bisphosphate

(PIP2)-producing enzyme phosphatidylinositol 4-phosphate 5-kinase alpha (PIP5Kα) in human hepatic cell carcinoma-derived HepG2 cells. Knockdown of Arf6 in HepG2 cells signifi cantly suppresses the HGF-dependent phosphorylation of Akt and cell proliferation. Phosphatidylinositol 3,4,5-trisphosphate (PIP3), which is generated from phosphorylation of PIP2 by the action of PI 3-kinase, recruits Akt to the plasma membrane and phosphorylates/activates it there to promote cell proliferation in response to agonist stimulation. Interestingly, Arf6 knockdown in HepG2 cells suppresses

HGF-induced PIP2 and PIP3 generation. Furthermore, we show that PIP5Kα is recruited to the HGF receptor (C-Met) in response to HGF stimulation. These results suggest that Arf6 recruits PIP5Kα to the stimulated C-Met and activates it to produce PIP2, which is converted to PIP3, which in turn activates Akt, thereby stimulating cell proliferation.

218 O-20

Phospholipase D2 is a key molecule to suppress tumorigenesis through activation of CD8+ T lymphocytes

Ngo Thai Bich Van, Tsunaki Hongu, Yuji Funakoshi and Yasunori Kanaho

Department of Physiological Chemistry, Faculty of Medicine and Graduate school of Comprehensive Human Sciences, University of Tsukuba

Phospholipase D (PLD) hydrolyzes the membrane phospholipid phosphatidylcholine (PC) to produce choline and the lipid messenger phosphatidic acid (PA). Two major PLD isozymes, PLD1 and PLD2, have been identifi ed in mammalian cells. Both PLD1 and PLD2 are involved in a wide variety of cellular events such as vesicular traffi cking, cell motility, and cell proliferation through their product PA. Recently, PLD1 has been reported to be involved in tumor growth through the promotion of tumor angiogenesis. However, involvement of PLD2 in tumorigenesis remains to be elucidated. Here, by using Pld2 knock out (Pld2-/-) mice, we demonstrate that PLD2 suppresses tumor growth through the regulation of CD8+ T cell activation. To investigate the functions of PLD2 in tumor growth, we subcutaneously transplanted B16 melanoma cells into WT and Pld2-/- mice. Interestingly, unlike the previous report on PLD1, the tumor growth of B16 melanoma syngraft was signifi cantly enhanced in Pld2-/- mice, indicating that PLD2 has a suppressive function in tumorigenesis. In the sections of tumors, the number of apoptotic B16 melanoma cells was decreased in Pld2-/- mice, whereas tumor angiogenesis was not affected, indicating that enhancement of tumor growth in Pld2-/- mice is attributable to inhibition of cell apoptosis. Since the immune system is known to regulate the survival of cancer cells, we next examined infi ltration of immune cells into the tumor. The number of CD8+ T lymphocytes in the tumor was signifi cantly decreased in Pld2-/- mice, whereas that of CD4+ helper T lymphocytes was not changed. In addition, the percentage of activated CD8+ T cells was reduced in the spleen of Pld2-/- mice. Production of interleukin-2, a cytokine secreted from the activated T cells, was also decreased in CD8+ T cells lacking PLD2. Moreover, in vitro proliferation of CD8+ T cells isolated from Pld2-/- mice was also inhibited. Collectively, these results indicate that PLD2 plays a key role in the activation of CD8+ T lym- phocytes, thereby regulating tumorigenesis.

219 O-21

GPNMB impacts to invasive properties of bladder cancer

Tomokazu Kimura1,2, Yukari Okita2, Yukihide Watanabe2, Hiroyuki Suzuki2, Hiroyuki Nishiyama1 , Mitsuyasu Kato2

1Department of Urology, Faculty of Medicine, University of Tsukuba 2Department of Experimental pathology, Faculty of Medicine, University of Tsukuba

Glycoprotein nmb (GPNMB) is a type1 transmembrane glycoprotein. GPNMB is known to play various roles on epithelial-mesenchymal transition, anchorage-independent growth, and tumorigenicity in cancer cells. Recent evidence describes that GPNMB expression correlates with metastasis and poor prognosis of the patients with several cancer. We evaluated how GPNMB impact on invasion of bladder cancer cells. To investigate how GPNMB contributes to the aggressive phenotype, we knocked it down by short hairpin RNA or over expressed human GPNMB in invasive bladder cancer cell lines. We performed the transwell assay with matrigel coating to evaluate the invasive activities of the manipulated cancer cells. We also checked the phenotype in vivo by using subcutaneous and orthotopic graft models, chemical carcinogenesis models in mice, and human bladder cancer specimens. In addition, to fi nd out the important domains for invasion, we made several point mutants of GPNMB and transfected them to cancer cells, and evaluated their invasion as well. The short hairpin RNA targeting GPNMB signifi cantly suppressed invasive ability in bladder cancer cells. Conversely, overexpressing GPNMB greatly promoted invasiveness. In vivo study, tumor size and volume didn’t show signifi cant difference in subcutaneous and orthotopic graft models. However, in subcutaneous model, intraperitoneal metastases were seen in the mice which were injected the cells with GPNMB overexpression but not mock cells. When these cells injected orthotopically, muscle invasion and intraperitoneal metastasis were detected. By immuno-histochemical staining, the expression pattern of GPNMB changed among from normal bladder mucosa to cancer cells in carcinogenic model. And we could also see the same trend in human specimens. When we changed from tyrosine to phenylalanine at 515 in hemITAM (immunoreceptor tyrosine-activated motif) of GPNMB, the cells transfected with this mutant could not promote the invasion compared to wild type GPNMB. We found that GPNMB is correlated to invasive properties of bladder cancer.

220 O-22

BCL6 methylation in human peripheral T-cell lymphoma

Shoko Nishizawa1, Mamiko Sakata-Yanagimoto1,2,3, Hideharu Muto2,3 and Shigeru Chiba1,2,3

1Hematology, Comprehensive Human Biosciences, University of Tsukuba 2Hematology, Faculty of Medicine, University of Tsukuba 3Hematology, University of Tsukuba Hospital

Angioimmunoblastic T-cell lymphoma (AITL) is a distinct subtype of peripheral T-cell lymphoma (PTCL). AITL tumor cells are known to have features of follicular helper T cells (TFH), including high expression of BCL6, which encodes a master transcription factor for TFH differentiation. We previously reported that TET2 and IDH2, encoding epigenetic regulators, are frequently mutated in AITL and AITL-like PTCL, and that TET2 knockdown mice developed T-cell lymphoma with TFH features. Objective of my research is to clarify the impact of TET2 mutations on methylation of BCL6 locus in human PTCL samples. Genomic DNA was extracted from tumors of human PTCL and B-cell lymphoma samples, and was subjected to bisulfi te conversion. Bisulfi te PCR was performed for BCL6 locus, CpG island 38 and 27. Methylation status was examined by high-throughput sequencing on Ion PGM. Hypermethylation was defi ned as the average levels of methylation being higher than 5.5%. Hypermethylation of BCL6 locus was more f requent i n PTCL sa mples t ha n B - cell ly mphoma samples (PTCL vs B-cell lymphomas: 9/42 vs 0/37 (p<0.05) at CpG38, 7/42 vs 1/37 (p>0.05) at CpG27). PTCL samples with TET2 mutations were more frequently hypermethylated than those without TET2 mutations (PTCL with TET2 mutations vs PTCL without TET2 mutations: 8/22 vs 1/17 (p>0.05) at CpG38, 6/22 vs 0/17 (p<0.05) at CpG27). There was no relationship between PTCL samples with or without IDH2 mutations (PTCL with IDH2 mutations vs PTCL without IDH2 mutations: 4/16 vs 3/6 (p>0.05) at CpG38, 4/16 vs 2/6 (p>0.05) at CpG27). Deregulated BCL6 expression caused by hypermethylation and TET2 mutations may result in skewed TFH differentiation and might eventually contribute to development of AITL/PTCL in patients as well as TFH-featuring T-cell lymphoma in TET2 gene-trap mice.

221 O-23

A spatial cell lineage model for healthy and diseased epithelial tissues

Seth Amin Figueroa1,2 and Qing Nie1,2

1Department of Biomedical Engineering, University of California, Irvine 2Center for Complex Biological Systems, University of California, Irvine

In organisms, proper tissue and organ development and maintenance must be precisely timed and spatially coordinated to ensure proper function. This can be challenging both to develop and to maintain in the complex environments present in organism, and thus robust regulations must be present to ensure effective development, maintenance, and regeneration. One major mystery is how diseases hinder the formation of a healthy stratifi ed epithelia and lead to different morphologies of the tissue. Two such diseases are Psoriasis and Acanthosis Nigricans, which result in a distorted and thickened epidermis. Here, we explore cellular and physical properties of stratifi ed epithelia and their effects on tissue formation using a spatial model of multistage cell lineage tissue growth in two dimensions. The model is able to recapitulate a variety of healthy epithelial tissue shapes and stratifi cation of different cellular types. Moreover, varying keratinocyte proliferation and cell apoptosis can mirror attributes of distorted tissues found in Psoriasis, such as elongated rete ridges and hyperkeratosis. By changing the physical properties of the apical and basal boundaries we can induce the formation of a stiff, fl at, plaque-like psoriatic tissue, or cause papillomatous elevations found in Acanthosis Nigricans. This study provides insight into how stratifi ed epithelia may achieve a variation of morphologies, and how diseases may change cellular or physical properties to distort the shapes and compositions of the tissue.

222 O-24

Structural dynamics of the endoplasmic reticulum mediated by cytoskeleton modifi es luminal protein transport

Jorge Toledo1,2,3,, Mauricio Cerda2,3, Felipe Santibáñez2,3, Felix Urra4, Claudia Reyes,1,2,3, Daniela Flores2,3, Javiera Bruna2,3, Cesar Cardenas4, Steffen Härtel2,3, Andrés Couve1,3

1Laboratory of Cellular and Molecular Neurobiology 2Laboratory of Scientifi c Image Analysis, SCIAN-Lab 3Biomedical Neuroscience Institute (BNI), University of Chile 4Laboratory of Cellular-Metabolism and Bioenergetics, University of Chile

Introduction: The endoplasmic reticulum (ER) is a fundamental organelle for membrane and secreted protein synthesis and traffi cking in eukaryotic cells. Membrane-bound ribosomes translate and transfer proteins to the ER lumen for subsequent subcellular targeting or secretion. Protein transport is key to ER function, and passive diffusion is believed to be the predominant underlying mechanism. However, since the ER is a continuous network that undergoes major structural changes, we state and assess the structural dynamics as an additional mechanism to control transport of luminal proteins. Materials and methods: ER in COS-7 cells was visualized by spinning-disk optical microscopy using transfected mRFP-KDEL. We modifi ed structural-dynamics through pharmacological treatments that alter cytoskeleton stability, molecular motors and the energetic metabolism. Through analysis of fl uorescence fl uctuation we defi ned a dynamics index (DI). Protein transport was examined by fl uorescence recovery after photobleaching (FRAP), obtaining a diffusion coeffi cient (D). We evaluated changes in D after modifying the structural-dynamics of the ER network by different kind of drugs. Results: Measurements of D indicate that diffusion of luminal proteins in micro-regions is slower than in larger regions. Our fi ndings also indicate that D depends on ER-dynamics but not on network-structure or cell morphology. Discussion: We speculate that ER-dynamics, generated by local cytoskeletal modifi cations, is an active mechanism which, in addition to passive diffusion, contributes to the transport of ER luminal proteins. Funding: ICM-P09-015-FONDECYT-1090246-3110157-3140447, MECESUP-CONICYT- scholarship

223 O-25

Identifi cation of a novel neuronal group that regulates REM- NREM sleep switching

Mitsuaki Kashiwagi1, Mika Kanuka1, Masashi Yanagisawa1,2, Yu Hayashi1,3

1WPI-International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba 2University of Texas Southwestern Medical Center 3Japan Science and Technology Agency (JST), PRESTO

Sleep disturbance is a major medical and social problem. Sleep is composed of two distinct states: REM (rapid eye movement) sleep and NREM (non-REM) sleep. NREM sleep accounts for a considerable time spent asleep, and REM sleep is the major source of dreams. Representative sleep disorders such as narcolepsy and insomnia accompanying depression are characterized by dysregulated emergence of REM sleep episodes. To understand these sleep disorders and develop new treatment strategies, it is important to elucidate the brain circuitry that governs REM-NREM sleep transitions. However, since the discovery of REM sleep in 1953, the neurons responsible have remained controversial. Especially, the neurons that negatively regulate REM sleep were poorly understood. Here, to clear the brain circuitry that governs REM-NREM sleep transitions, we utilized genetic tools in mice to artifi cially control neural activity in a cell-type specifi c manner. As a result, we identifi ed a small group of peptidergic neurons that strongly suppress REM sleep. Activation of these neurons using the DREADD (Designer Receptors Exclusively Activated by Designer Drugs) technique resulted in almost complete loss of REM sleep for several hours. These neurons were located in the brainstem pons, which was previously shown to contain neurons that positively regulate REM sleep. Our studies are expected to contribute to understanding the central circuitry regulating REM-NREM sleep switching.

224 O-26

Systematic Behavioral Screening of Sleepy and Dreamless, Newly Identifi ed Mouse Pedigrees with Sleep Abnormalities

Takato Honda1,2,3, Tomoyuki Fujiyama1, Chika Miyoshi1, Makito Sato1, Hiromasa Funato1 and Masashi Yanagisawa1

1International Institute for Intergrative Sleep Medicine (WPI-IIIS), Universitu of Tsukuba 2Ph.D. Program in Human Biology, School of Integrative and Global Majors, University of Tsukuba 3JSPS Research Fellow (DC1)

Why and how do we sleep? – this is a very simple but diffi cult question to answer. We human beings spend nearly one-third of our lives asleep. However, the mechanism and function of sleep remains unclear. Understanding the neurobiological basis for “sleepiness” has not only a biological signifi cance, but also a great benefi t for human society. In Japan, it has been reported that the economical losses reach 3.5 trillion yen per year due to people’s troubles with sleep. Moreover, sleep disorders have reciprocal risk relations with metabolic syndromes, as well as cognitive and mood disorders. It is required to crack this black box and develop a way to control it. As a biggest unrevealed issue in sleep biology, the mechanism for homeostatic sleep/wakefulness regulation, as well as the neural substrate for “sleepiness”, remains a mystery. To make a breakthrough in this question, our laboratory has initiated a large-scale forward genetic screen of sleep/wake abnormalities in mice, based on somnographic (EEG/EMG) measurements, the gold standard in mammalian sleep/wake assessment. We have so far screened >7,000 heterozygous ENU-mutagenized mice and established 10 pedigrees exhibiting heritable and specifi c sleep/wake abnormalities. By combining linkage analysis and whole- exome sequencing, we have so far identifi ed three mutations: Sleepy and Sleepy2, causing marked hypersomnia (increased non-REM sleep), and Dreamless, causing short and highly fragmented REM sleep. Since these dominant mutations cause very strong phenotypes, we expect that the mutated genes play central role for regulating sleep/wake amounts. Furthermore, these mutant mice can be a sleep disease model to approach the relationship between sleep and other cognitive and mental functions such as learning and memory, depression, anxiety, sociability and more. Here, we examined the following series of behavioral analyses for both Sleepy and Dreamless mutant mice: 1) Morris water maze, 2) forced swim test, 3) tail suspension test, 4) open fi eld test, 5) novel object recognition, 6) elevated plus maze, 7) social interaction test, 8) sucrose preference, 9) nest building, and 10) fear conditioning. We detected signifi cant behavioral phenotypes in these mice, including an impaired hippocampus-dependent memory formation in Dreamless, and a depression-like phenotype of Sleepy mutant mice. These results of behavioral test battery provide us the landmark information to approach the link between sleep and other behaviors.

225 O-27

GABAergic neurons in the pontomedullary tegmentum control sleep and wakefulness

Daiki Nakatsuka1, Takeshi Kanda1, Tatsuya Kurokawa1, Yoan Cherasse1, Yukiko Ishikawa1, Masashi Yanagisawa1,2

1International Institute for Integrative Sleep Medicine (IIIS), University of Tsukuba 2University of Texas Southwestern Medical Center

Although various subcortical brain structures are thought to regulate the states of sleep and wakefulness, the present models of the regulatory mechanisms are still incomplete due to a large number of missing elements. Toward identifi cation of a novel cell group responsible for sleep regulation, we systematically and specifi cally inhibited fi ring of neurons using chemogenetic approach, and investigated if their fi ring affects sleep. To silence neural fi ring in various areas, we expressed the inhibitory ‘Designer Receptors Exclusively Activated by Designer Drugs’ (DREADD) hM4Di, which induce neural inhibition by binding of the otherwise inert compound Clozapine N-oxide (CNO). Region- and cell-type specifi c expression of hM4Di was achieved by local injection of Cre-inducible adeno-associated virus (AAV) vectors encoding hM4Di into the GAD1-Cre mice, in which Cre recombinase is expressed exclusively in GABAergic neurons. Histological studies showed that 94.2% of hM4Di-expressing neurons were GAD1-positive, suggesting hM4Di was specifi cally expressed in GABAergic neurons. Patch-clamp recordings revealed that CNO suppressed spontaneous discharge of hM4Di- expressing neurons. Analysis of sleep patterns after intraperitoneal administration of CNO indicated that DERADD-mediated inhibition of GABAergic neuron in the medial vestibular nucleus (MVN) increased the total amount of NREM sleep, and decreased that of both REM sleep and wakefulness. To trace the projection patterns of GABAergic neurons in the MVN, Cre-inducible AAV vector encoding GFP appended to a palmitoylation sequence of GAP43 (palGFP) which is effectively transported to axonal terminals was injected into the MVN of GAD1-Cre mice. Their axonal projections were detected not only in the brain areas involved in vestibular systems such as oculomotor nucleus and the nucleus of Cajal, but also in the brain areas related to the regulation of sleep and wakefulness such as the ventral tuberomammillary nucleus and the preoptic area. Our results suggest that MVN GABAergic neurons are the novel cell population contributing to the control of sleep and wakefulness.

226 O-28

Optogenetic mapping of network dynamic in basal ganglia

Brice de la Crompe1,2, Thomas Boraud1,2 and Nicolas Mallet1,2

1Univ. de Bordeaux, Institut des Maladies Neurodégénératives 2CNRS, Institut des Maladies Neurodégénératives

The basal-ganglia (BG) form a complex loop of nuclei connecting the cortex to the thalamus that is involved in action selection and decision-making. Synchronized oscillatory activities in BG neuronal circuits have been proposed to play a key role in coordinating information fl ow within and between neuronal networks. If synchronized oscillatory activities are important and necessary for normal motor function, their dysregulation in space and time can truly be pathological. Indeed, in Parkinson’s disease (PD), many studies have reported an increase in the expression level of neuronal oscillations contain in the beta (β) frequency range (15-30 Hz). These abnormal β oscillations have been correlated with two mains symptoms of PD: akinesia/ bradykinesia. However, which BG neuronal circuits generate those abnormal β oscillations, and whether they play a causal role in PD motor dysfunction is not known. The subthalamic nucleus (STN) is a key nucleus in BG that receives converging inputs from the indirect (i.e. globus pallidus) and hyperdirect (i.e. cortex) pathways. Here, we used a clinically-relevant rat model of PD combined with electrophysiological recordings and optogenetic toolboxes to investigate how selective manipulation of pallido-subthalamic inputs causally infl uence BG network dynamic. Our data provide new mechanistic information to help understand the generation and propagation of abnormal β-oscillations as well as they role on motor behavior.

Keywords: Parkinson’s disease, β-oscillation, basal ganglia, optogenetics, electrophysiological recording

227 P-9

A part of Agr-defi cient ‘stealth’ Staphylococcus aureus can regain its virulence during phagocytosis

Aya Takemura1, Kazuya Morikawa2

1PhD program in Human Biology, University of Tsukuba 2Faculty of Medicine, University of Tsukuba

Staphylococcus aureus is a commensal bacterium that naturally inhabits the nasal cavity of mammals. It is also an opportunistic pathogen that carries a variety of virulence factors. Expression of most S. aureus virulence factors is controlled by the accessory gene regulator (agr) locus that consists of AgrABCD (cell density ‘quorum’ sensing system) and RNA III (functional RNA regulating translation of virulence factors). The lack of agr system shuts down a series of toxin production, while it allows expression of cell-surface adhesins. Such an agr negative trait confers survival advantages in chronic infections and persistence within host cells: indeed, variants carrying agr mutations are often isolated from chronically infected patients. These agr negative ‘stealth’ cells have been considered to be irreversible, genetically dead-end variants. Here, we fi rst report two variants carrying reversible agr mutations from S. aureus MW2. One had duplication, and partial inversion in agrC. Another had a point mutation in agrC. The reversion frequencies were ~10-2. GFP reporter analysis showed that their revertant subpopulation cannot activate the agr system when it is a minority within the agr-defi cient population. In contrast, the revertants regained the agr activity during the phagocytosis. Our results suggest that reversible agr variants play an important role to sustain the genetic information of the agr locus that needs to be mutated in a part of infection processes.

228 P-10

Prp18, a pre-mRNA processing factor 18, promotes infl uenza virus RNA synthesis through NP chaperone activity

Moeko Minakuchi1, Kenji Sugiyama1,2, Tadasuke Naito1#, Kyosuke Nagata2

1Department of Infection Biology 2Faculty of Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba #Present address: Department of Microbiology, Kawasaki Medical School

The genome of infl uenza type A virus is eight-segmented and single-stranded RNAs of negative polarity and exists as a ribonucleoprotein (termed vRNP) complex with nucleoprotein (NP) and viral RNA-dependent RNA polymerases consisting of three subunits, PB1, PB2, and PA. The template for viral RNA synthesis is not naked RNA but vRNP complexes. vRNP plays the central role in viral RNA synthesis, but for the maximal synthesis level host-derived factors are required. A variety of host factors that interact with viral proteins have been identifi ed by physical interaction assays and proteomics approaches. However, only a few host factors have been investigated by functional analyses for viral RNA synthesis. Previously, we established a replication and transcription system of the infl uenza viral RNA genome in Saccharomyces cerevisiae, and developed using a single-gene deletion library of yeast a system to screen host factors involved in the viral RNA synthesis. Using this, we found several host factor candidates affecting viral RNA synthesis, and among them we have identifi ed a new host factor, pre-mRNA processing factor 18 (Prp18), which is known as a splicing factor for the catalytic step II in pre-mRNA splicing process. The target of the Prp18 was shown to be NP and the viral polymerase. Gel shift assays showed that Prp18 facilitates formation and dissociation of NP-RNA complexes. In infected Prp18 knock-down cells, the level of accumulation of viral RNA (vRNA), complementary vRNA (cRNA), and viral mRNAs were reduced. It is suggested that the activity of viral RNA syntheses were decreased. Based on these results, it is suggested that Prp18 accelerates the infl uenza viral RNA synthesis possibly as an NP chaperone.

229 P-11

The Arf6-specifi c GTPase-activating protein ARAP3 regulates breast cancer cell invasion

Yohei Yamauchi1, Tsunaki Hongu1, Hideki Yamaguchi2, Yuji Funakoshi1, Norihiko Ohbayashi1, and Yasunori Kanaho1

1Department of Physiological Chemistry, Faculty of Medicine and Graduate School of Comprehensive Human Sciences,University of Tsukuba 2Division of Refractory and Advanced Cancer, National Cancer Center Research Institute

A major cause of cancer-related death is the distant metastasis. Metastatic cancer cells must initially invade the basement membrane and extracellular matrix (ECM) by forming invadopodia. Invadopodia are actin-rich protrusions at the plasma membrane of cancer cells with crucial functions in ECM degradation. The small GTPase ADP-ribosylation factor 6 (Arf6) regulates membrane traffi cking and actin remodeling, and has been reported to be involved in cancer cell invasion. Arf6, like other small GTPases, functions as the molecular switch by cycling between a GDP-bound inactive and GTP-bound active form, the latter of which interacts with downstream effector molecules to regulate cellular functions. Several recent studies have indicated that as well as activation, inactivation of Arf6 is important for cancer cell invasion. However, it has not yet been clearly understood how Arf6 is inactivated in cancer cells and whether cycling of inactive and active Arf6 states is crucial for cancer cell invasion. We hypothesized that a GTPase-activating protein (GAP), which promotes inactivation of Arf6, is involved in cancer cell invasion by enhancing the cycling of Arf6 states. The expression analysis of Arf6-specifi c GAPs in the invasive breast cancer cell line MDA- MB-231 cells and non-invasive breast cancer cell line MCF7 cells revealed that expression level of ARAP3, of 9 Arf6-specifi c GAPs so far identifi ed, was higher in MDA-MB-231 cells than in MCF7 cells. Knockdown of ARAP3 in MDA-MB-231 cells signifi cantly inhibited EGF-dependent invadopodia formation, thereby suppressing cancer cell invasion as assessed by the matrigel invasion assay. Furthermore, Arf GAP activity of ARAP3 was absolutely required for the invadopodia formation. These results suggest that the Arf6-specifi c GAP ARAP3 functions in invadopodia formation and promotes cancer cell invasion by regulating the cycling of Arf6 states.

230 P-12

MafB expressed in Osteoclast Precursors regulates osteoclastogenesis through M-CSF signaling

Yuki Tsunakawa1,2, Michito Hamada1,3, Yurina Matsunaga1, Hyojung Jeon1, Zeinab Kosibaty1, Kyoko Sawaguchi1 and Satoru Takahashi1,3

1Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba 2School of Integrative and Global Medicine, Ph.D. Program in Human Biology, University of Tsukuba 3International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba

As the importance of osteoclast function is known to be essential for bone maintenance by constantly resorbing old bone, limited researches have elucidated their differentiation process other than being mediated by RANKL and M-CSF cytokines. To extend this fi eld, we focused on Multicent r ic Car pal Tarsal Osteolysis (MCTO), a disease by excess osteoclasts differentiation from human MAFB gene mutation. Although Kim et al., (2007)’s study demonstrated the MafB involvement in osteoclastogenesis, we intend to broaden the spectrum by reporting a new function of MafB interacting with M-CSF signaling in osteoclast development. MafB is a transcription factor which negatively regulates M-CSF during monocyte and macrophage development. Since macrophage share common progenitors to osteoclasts, we hypothesized that Maf B is essential in osteoclastogenesis as well. Initially, to test the specifi city of MafB and M-CSF, bone marrow cell (BM cells) colonies were counted from Mafb-/- and WT mice when treated with M-CSF and GM-CSF, another cytokine involved in macrophage development. As a result, more colonies from Mafb-/- mice were observed compared to WT, yet, no signifi cant differences were seen between GM-CSF treated cells. Secondly, to identify the origins of MafB expressing BM cells, Mafb-/- and WT mice cells were tagged with linage markers and Hematopoietic markers (c-kit, Sca-1), sorted using fl owcytometry and colony numbers generated were counted under M-CSF treatment. Results showed higher number of colonies from Mafb-/- derived Lin-Sca-1-c-Kit- cell population, a newly identifi ed osteoclast progenitor, compared to WT. In addition, fl owcytometic analyses on these progenitor cells of Mafb-/- GFP knock in analyses were conducted to further clarify MafB expressing cells. GFP signals from Knock in mice at CD115 (M-CSF receptor) expressing cells were high, which correlates to osteoclast progenitors previously reported, included in the R3 cells from the bone marrow (Charles et al., 2012). In conclusion, these results illustrate the vital contribution of MafB as a negative regulator for osteoclastogenesis in a newly identifi ed osteoclast progenitor cells. Although various questions still remain to be untied such as the osteoclast differentiation effi ciency of these cells, fi ndings on the MafB function in the new osteoclast progenitor though M-CSF in vitro will certainly contribute to bone diseases becoming history one day.

231 P-13

Novel Imaging Technique for Atherosclerosis

K.M.G.M.K.K.Kulathunga1, Mao Otake1,3, Michito Hamada1, Mai Thi Nhu Tran1, Tomoki Sakasai 2, Yoshihiro Miwa2 and Satoru Takahashi1

1Department of Anatomy and Embryology, University of Tsukuba 2Department of Molecular Pharmacology, University of Tsukuba 3Faculty of Medicine, University of Tsukuba

Quantitative analysis of progression of Atherosclerotic plaque has an utmost importance in better understanding of the disease itself and also in validating current therapeutic measures and in establishment of novel effective medical and surgical interventions for atherosclerosis. Whether there are many established diagnostic-imaging methods for atherosclerosis they are not effective and user friendly in prolong progressive disease surveillances frequently used in preclinical animal experiments of new drug discovery procedures. Here we are addressing the need for an in vivo noninvasive live animal atherosclerosis visualizing method in mice using stable nontoxic Near Infrared Fluorescent Protein (iRFP), which is not published before in use of atherosclerosis imaging. Moreover it is demonstrated the ability of this method to be used as in vivo continued monitoring atherosclerotic imaging technique with out any invasive procedures but only using the IVIS imaging system with in few seconds. Red fl uorescence with an excitation wavelength of 690 nm and an emission wavelength of 713 nm is detected by this system. It is already reported the direct involvement of circulatory macrophages in the progression of lipid rich Atherosclerotic lesion. Our new imaging system targets the iRFP transgenic macrophages in the atherosclerotic lesion. iRFP transgenic mouse bone marrow cells transplanted to X ray irradiated Low Density Lipoprotein Receptor Knock Out (LDLR KO) mice model is used through out the experiment. After conforming the establishment of the iRFP TG hematopoietic system in LDLR KO mice, progression of atherosclerosis was induced by feeding atherogenic diet. Progression of Atherosclerosis was imaged from day 0 to 10 weeks in 2 weeks intervals. iRFP TG hematopoietic system transplanted LDLR KO mice fed with normal diet and Wild type (WT) hematopoietic system transplanted LDLR KO mice were used as controls to conform the imaged fl orescence is strictly from the atherosclerotic lesion. The results suggest that our new iRFP based atherosclerosis imaging system can be able to image the atherogenic lesion accurately with highly specifi c atheroma targeting capability for long term experimental procedures with low variations. We believe that with few more advancements our iRFP atherosclerosis imaging mouse model can be used as a useful novel tool in vivo live imaging which has a great potential to accelerate effective diagnosis and drug development procedures for atherosclerosis.

232 P-14

Gene Analysis of “Liver-Insulin Producing Cells” Using MIP- GFP Mouse

Yunshin Jung, Ruyi Zhou, Hisashi Oishi and Satoru Takahashi

Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba

Diabetes is caused when there is insulin defi ciency or insulin resistance. Regardless of their different cause of diabetes, the fi rst line of the treatments is focused on increasing insulin production, which alleviate symptoms for a short period and cannot stop complications. Therefore new therapies are required. One of the challenging methods to overcome these problems is de novo insulin production from other organs. In vivo insulin producing cells were fi rst produced from liver in 2000 by overexpressing one of the key transcription factors of beta cell development, Pdx1. Since then few more elements were reported to convert liver cells into insulin producing cells: Neurod1 in 2003 and Mafa in 2005. Even though the combination showed the best effects on liver conversion into beta like cells, two major problems still remain: transient insulin expression and poor glucose responsiveness. In this study, we report how the “current effector cells”, hepatic cells capable of expressing insulin, are different from beta cells and liver cells using genomic analysis. We fi rst isolated the effector cells from liver using mouse insulin promoter (MIP)-GFP reporter mouse that express GFP under the control of the insulin promoter. Upon the injection of Pdx1, Nuerod1 and Mafa using adenovirus vector through tail vein, GFP was expressed in liver, which was further sorted by FACS. Gene analysis on the effector cells was carried out using qRT-PCR as well as microarray in comparison with real beta cells and liver cells. Both analyses reveled that beta- cell related genes including Sox17, Nkx6.1 and Pax4 were upregulated when compared to liver cells, but not comparable to the real beta cells, which might explain the incomplete conversion of the liver. Moreover promoter analysis and pathway analysis indicated not only that whole gene sets related to insulin secretion were increased but also that infl ammatory cascades were also highly augmented. Therefore, this research proposes that currently identifi ed converting factors are insuffi cient for converting liver into insulin producing cells.

233 P-15

Both Chondroitin Sulfate N-acetylgalactosaminyltransferase-1 and -2 are Necessary for Endochondral Ossifi cation

Miki Shimbo1,2, Takashi Sato3, Kozue Hagiwara3, Risa Okada1, Hiromasa Wakui1, Hisashi Narimatsu3, Satoru Takahashi1, and Takashi Kudo1

1Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba 2Doctral Program in Biomedical Science, Graduate School of Comprehensive Human Sciences 3Biotechnology Research Institute for Drug Discovery, Department of Life Science and Biotechnology, AIST

Chondroitin sulfate (CS) is a sulfated glycosaminoglycan chain that consists of repeating disaccharide units, which is synthesized by 6 glycosyltransferases. In cartilage, numerous CS exists as side chains of aggrecan and become a main component of extracellular matrix (ECM). Although CS is widely known to play an important structural role in cartilage, its role in chondral development is unclear. Moreover, the mechanism how CS is synthesized by glycosyltransferases in vivo remains largely unknown. Previous studies have suggested that two glycosyltransferases, Csgalnact-1 (t1) and Csgalnact-2 (t2), are most important for CS synthesis initiation. To investigate the role of CS in chondral development and a synthetic mechanism of CS in vivo, here, we generated cartilage specifi c t1 and t2 double knockout mice (Col2-cDKO). Most Col2-cDKO mice died shortly after birth due to respiratory failure, but a few newborn mice were survived. Interestingly, although the Col2-cDKO mice had no difference in body weights at E18.5, they showed a severe abnormality in postnatal skeletal development, with almost 50% reduction in body weight compared to that of wildtype. Histological analysis of growth plate in Col2-cDKO proximal tibial epiphyseal cartilage at E18.5 and P14 revealed a disrupted endochondral ossifi cation characterized by reduction of the glycosaminoglycan content in ECM, an abnormal shape of chondrocytes, and disorganization of the growth plate structure. Immunohistochemical analysis showed Col2-cDKO chondrocytes undergo less proliferative state but more apoptotic state. In addition, reduction and altered pattern of aggrecan expression was observed. Since aggrecan resides in ECM, chondrocytes themselves were thought to be intact. As expected, primary culture of chondrocytes from Col2-cDKO knee cartilage showed same proliferating rate as that of wildtype. Quantitative RT-PCR demonstrated that expression of several signal genes indispensable for proper chondral development was decreased in Col2- cDKO knee cartilage. Altogether, these results suggest that t1 and t2 play a critical role in initiation of CS synthesis, and the CS is required for proper endochondral ossifi cation.

234 P-16

MafB defi ciency impairs the apoptotic cell clearance of macrophages

Keigo Asano, Tran Thi Nhu Mai, Risako Shiraishi, Michito Hamada and Satoru Takahashi

Anatomy and Embryology, Faculty of Medicine, University of Tsukuba

Macrophage is one of the main phagocytes that recognizes and engulfs apoptotic cells to maintain peripheral immune tolerance. The failure of apoptotic cell clearance by macrophages induces autoimmunity. Although most of the apoptotic cell recognition factors have been identifi ed, the mechanism of transcriptional regulation of these factors remains unknown. Transcription factor MafB belongs to the large Maf family share b-zip motif that mediate dimmer formation and regulate target genes by binding MARE (Maf recognition element) in the promoter region. MafB is specifi cally expressed in macrophages in hematopoietic cells and affects proliferation and differentiation of macrophage. In this study, we show that MafB is involved in apoptotic cells clearance. The depletion of MafB in macrophage decreases the expression of apoptotic cell recognition genes, especially C1qa, C1qb, C1qc, leading to the impairment of phagocytosis both in vitro and in vivo. While wild-type serum is able to recover phagocytosis in Mafb-/- macrophages, C1q-depleted serum could not rescue this phenotype. In addition, promoter analysis of C1q genes showed that MafB directly regulates expression of C1qa, C1qb and C1qc through the MARE in their promoter region. In Mafb-/- mice, production of anti ds-DNA antibody and anti nuclear antibody was increased. Moreover, knockdown analysis using siRNA of human MAFB and ChIP assay using anti-MAFB antibody showed that MAFB directly regulates the expression of C1Q genes in macrophage derived from human monocytic cell line THP-1. From this result, it is suggested that MafB is the regulator of C1q genes both in mice and humans. Overall, our results indicate that MafB might have a pivotal role in phagocytosis of apoptotic cells and inhibition of autoimmune disease through directly regulating the expression of C1q genes.

235 P-17

Establishment and Application of ROSA26 Halo-iRFP fl ox Mice and Non-invasive Fluorescence Imaging of Disease-model Mice

Tomoki Sakasai1, Yuka Sugiyama1, Junko Tanaka2, Shota Sakaguchi1, Kosuke Kawamura1, Seiya Mizuno2,3, Satoru Takahashi2,3, Yoshihiro Miwa2,3

1Graduate School of Comprehensive Human Sciences, University of Tsukuba 2Faculty of Medicine, University of Tsukuba 3Laboratory Animal Resource Center, University of Tsukuba

Experiments using animals are necessary to fi gure out processes of various diseases, because they are results of breakdown of higher-order life phenomena. Invasive methods such as surgery might disturb intravital circumstances and make it diffi cult to observe for long term. It is a powerful solution for the problem to visualize animals non-invasively with near- infrared (NIR) light. NIR light with wavelength from 650 nm to 900 nm is absorbed poorly by mammalian tissues, then it is easily transmitted through the body of mice. In 2009, the fi rst NIR fl uorescent protein (FP), IFP1.4 was reported by Tsien’s group and in 2011, improved NIR FP, iRFP was reported by Verkhusha’s group. Currently, we aim to establish NIR non-invasive imaging using iRFP. In this study, we have attempted to establish Halo-iRFP fl ox mice, by inserting the DNA fragment carrying CAG-loxP-HaloTag7-loxP-iRFP into the ROSA26 locus of mouse ES cells derived from C57BL/6J. The HaloTag-positive ES cells were selected by staining with HaloTag Oregon Green ligand and were transferred into the embryos to create chimeric mice. Then, we stained the leukocytes from mice with HaloTag TMR ligand to analyze the expression by FACS. iRFP can be expressed in the specifi c tissues and organs of Halo-iRFP fl ox mice by crossing with various Cre-expressing mice. We changed these mice into albino for sensitive and continuous fl uorescence imaging. These mice are crossed with Ayu-1-Cre mice which express Cre protein at the fertilized egg and Insulin1-Cre mice which produce Cre protein in β cells in the pancreas to check the function of Cre-loxP system. Therefore, we are establishing versatile experimental systems to make non-invasive fl uorescence imaging of disease-model mice.

236 P-18

Establishment of an analysis system utilizing protein degradation and near infrared fl uorescent proteins

Kosuke Kawamura1, Junko Tanaka2, Yoshihiro Miwa2,3

1Graduate School of Comprehensive Human Sciences, University of Tsukuba 2Faculty of Medicine, University of Tsukuba 3Laboratory Animal Resource Center, University of Tsukuba

Near infrared (NIR) fl uorescent proteins have excitation and emission maxima within the near infrared region, in which mammalian tissues have lower absorbance. Therefore they can be powerful tools for in vivo imaging. Another advantage of these proteins is that the excitation and emission wavelength do not overlap with those of conventional multi-color fl uorescent probes that utilize the visible range. By combining conventional probes with NIR fl uorescent proteins, we are able to establish a more complex analysis system. The purpose of this research is to establish an analyzing system with high time resolution. For this, we have tried to combine NIR fl uorescent proteins with a drug-controlled protein degradation system. We have previously developed TetDegraton system, which uses tetracycline antibiotics to control protein degradation. Also we used a fl uorescent probe called, Fucci (fl uorescence ubiquitination cell cycle indicator), which visualizes the cell cycle with different colors, using cell cycle dependent protein degradation. We applied this assay system for analyzing cell cycle dependent gene expression phenomenon.

237 P-19

Roles of GPNMB in Breast Cancer Stem Cells

Chen Chen, Yukari Okita, and Mitsuyasu Kato

Department of Experimental Pathology, Faculty of Medicine and Graduate School of Comprehensive Human Sciences, University of Tsukuba

Worldwide, breast cancer is the leading type of cancer in women. Cancer metastasis causes more than 90% of lethality among breast cancer patients. Especially triple negative breast cancer (TNBC) that is negative for three common markers: estrogen receptors (ER), progestin receptors (PR), and human epidermal growth factor receptor-2 (HER-2), shows relatively poorer prognosis than other subtypes. So far treatment options for TNBC patients are very limited. Cancer stem cells were fi rst identifi ed in acute myeloid leukemia in 1997. In 2003, Dr. Michael Clarke succeeded in fi nding cancer stem cells in breast tumors. From that on cancer stem cells are believed to be the root cause of tumor recurrence and metastasis. Transmembrane Glycoprotein NMB (GPNMB) has been reported to be overexpressed in various cancer types, including melanoma, glioma, and breast cancer, especially in TNBC, and it is one of poor prognostic markers. Our previous study showed that enhanced expression of GPNMB confers epithelial mesenchymal transition (EMT) and tumorigenic potential to normal mammary gland epithelial cells. Moreover, some other studies found that GPNMB is associated with invasion, and bone metastasis of breast cancer. CDX-011 (glembatumumab vedotin) is an anti-tumor drug-conjugated anti-GPNMB antibody. CDX-011 has been developed for the treatment of GPNMB-expressing cancers. In a phase II trial for breast cancer patients with metastasis, treatment by CDX-011 was found to increase the free and overall survival in TNBC patients. GPNMB is a promising target for cancer therapy. In this study, I focus on the regulation of GPNMB in breast cancer stem cells. First, I compared gene expression levels in two different culture conditions, three-dimensional (3D) sphere culture condition and two-dimensional (2D) normal cell culture condition. Sphere formation is a function of stem cells. The results show that GPNMB and Sox2, a stem cell marker, are expressed at higher levels in spheres. I am going to isolate GPNMB high cells from spheres and examine whether GPNMB is required for cancer stemness maintenance or not.

238 P-20

Histone demethylase LSD1 is important for the endodermal organ development in zebrafi sh

Christina-Sylvia Andrea, Yuji Fuse and Makoto Kobayashi

Molecular and Developmental Biology, Faculty of Medicine, University of Tsukuba

Epigenetic mechanisms are known to be regulating the switching between multipotent progenitor cells and lineage-restricted differentiated cells. A major epigenetic mechanism is histone methylation/ demethylation, which has been shown to be associated with a variety of biological processes, regulating the differentiation of progenitor cells via transcriptional activation or repression. Histone lysine demethylases have been implicated in the decision between maintaining multipotency and differentiation, with such a histone demethylase being Lysine Specifi c Demethylase 1 (LSD1). From previous studies, our research group has managed the isolation and characterization of an LSD1 mutant zebrafi sh line, lsd1it627, which has a non-sense mutation causing specifi c defects in hematopoiesis during early embryogenesis, indicating that LSD1 is a key regulator in primitive hematopoiesis. In this study we present yet another phenotype that was observed in lsd1it627 embryos, in which endodermal organs, such as swim bladder, liver and pancreas, appear not to develop normally. The swim bladder seams not to be infl ated and the expression of swim bladder- specifi c marker anxa5b, liver-specifi c marker fabp10 and pancreas-specifi c marker trypsin was weak in lsd1it627 embryos, even though pan-endodermal marker foxa3 was expressed normally. These fi ndings suggest that differentiation steps of these endodermal organs may be impaired, with LSD1 being closely involved. LSD1 has been implicated by previous studies in tumor formation of endodermal organs, such as liver, lung, and pancreas. Our fi ndings may provide new insights on the epigenetic control of the endodermal organ formation during embryonic development, organogenesis and carcinogenesis.

239 P-21

Simple generation of hairless mice by the CRISPR/Cas9 system

Yoshikazu Hoshino1,2, Kanako Kato1, Saori Iijima1, Yoko Tanimoto1, Miyuki Ishida1, Satoru Takahashi1, Seiya Mizuno1, Fumihiro Sugiyama1, and Ken-ichi Yagami1

1Laboratory Animal Resource Center, University of Tsukuba 2Hoshino Laboratory Animals, Inc.

At present, in vivo imaging of mice is on the verge of becoming possible to analyze disease progresses non-invasively through reporter gene expression. Because the removal of hair improve accuracy of in vivo imaging, gene-modifi ed mice are often crossed to the Hos:HR-1 mutant mice which carried the hr gene mutation and exhibit the hair loss phenotype. However, it is time consuming to produce the mice carried both transgene for in vivo imaging and hr gene mutation by mating. In addition, there is the risk that genetic background of the transgenic mouse would be changed by mating. To solve this problem, we try to establish a simple method to generate hairless transgenic mice keeping its genetic background by CRISPR technology. Firstly, we construct two types of px330 vectors which target different genomic sequences in exon 3 of the hr. Then, these DNA vectors (5 ng/μL) were microinjected into pronuclear of C57BL/6J, respectively. Accordingly, induced hr gene mutations were found in many founders in each target (76.1% and 83.3%). Moreover, these genetic mutations were found in next generation. This our study clearly showed that hairless mice could be simply generated by CRISPR/Cas9 system, and this method might be useful for production the hairless transgenic mice keeping their genetic background and it will be contribute in vivo imaging studies.

240 P-22

Hypnotic and teratogenic effects of thalidomide can be dissociated

Yuki Hirose, Hiromasa Funato, and Masashi Yanagisawa

International Institute for Integrative Sleep Medicine (WPI-IIIS) University of Tsukuba

Thalidomide was sold as the “miracle” hypnotic agent in 1950’s. No deleterious side effects or lethality had been detected in rodent safety tests before going on market, because rodents do not exhibit thalidomide teratogenicity (see below) for unknown reasons. Thalidomide did not reduce REM sleep time in human, which brought about a more “natural” sleep. Thalidomide was prescribed for many people, especially pregnant women, in countries including Germany and Japan for several years. Unfortunately, it turned out that thalidomide caused phocomelia, severe developmental malformation of limbs, and was eventually taken off the market causing a big scandal. Recently, however, thalidomide and its derivatives have been reintroduced as immunomodulatory drugs, especially in the treatment of multiple myeloma. In 2009, Cereblon (CRBN) was identifi ed as the target molecule of thalidomide teratogenicity. CRBN acts as a substrate receptor in the Cullin4-ROC1-DDB1 ubiquitin ligase complex; thalidomide binds to CRBN and inhibits ubiquitination. Y384A and W386A (YW/AA) mutated CRBN was shown to lose the binding ability to thalidomide, while keeping normal ubiquitin ligase activity. CRBN YW/AA mutant zebrafi sh and chickens show a resistance to thalidomide teratogenicity. The mechanism of thalidomide’s hypnotic effect remains unknown. We questioned whether the CRBN-mediated ubiquitin/proteasome pathway was involved in thalidomide’s hypnotic effect. To resolve this question, we generated Crbn-YW/AA knockin (KI) mice, which we confi rmed to be resistant to thalidomide-induced inhibition of CRBN-dependent ubiquitination. We then recorded sleep EEG/EMG after thalidomide treatment in the KI and wildtype C57BL/6N mice. Thalidomide increased non-REM sleep time in a dose-dependent manner in wildtype mice. Thalidomide increased non-REM sleep time in Crbn-YW/AA KI homozygotes and heterozygotes similarly to wildtype littermates. Among all genotypes, there was no signifi cant difference in the delta power of non-REM sleep during 3 h after thalidomide treatment. We demonstrated that thalidomide had an identical hypnotic effect in Crbn-YW/AA KI mice, as compared to wildtype mice. This indicates that CRBN is not the target of thalidomide’s hypnotic effect. The hypnotic effect can be dissociated from the teratogenic effect of thalidomide, opening up the possibility to create a thalidomide-like hypnotic drug that does not possess teratogenicity.

241 P-23

A novel, small-molecule orexin type 2 receptor agonist improves narcoleptic symptoms in orexin-null mice

Hiromu Tominaga, Yoko Irukayama-Tomobe, Yasuhiro Ogawa, Yukiko Ishikawa, Shinobu Ambai, and Masashi Yanagisawa

International Institute for Integrative Sleep Medicine, University of Tsukuba

Narcolepsy-cataplexy is a neurological disease characterized by non-REM and REM sleep- related symptoms, such as excessive sleepiness and cataplexy. Cataplexy is a symptom of sudden bilateral skeletal muscle weakening without impairment of consciousness. Narcolepsy- cataplexy is caused by the loss of orexin signaling. Previous reports have shown that ectopic expression of a prepro-orexin transgene in the brain or central administration of orexin-A prevents cataplexy and improves wakefulness in narcolepsy-cataplexy model mice. Orexin acts on two receptors, OX1R and OX2R, and previous reports suggest that OX2R signaling is necessary for inhibition of cataplexy and increase of wakefulness. Therefore, orexin receptor agonists, especially OX2R agonists, are expected to be effective as a novel therapeutic drug for narcolepsy-cataplexy. We investigated the effects of a novel OX2R-selective agonist, YNT-185, on narcoleptic mice by in vivo treatments. We used orexin knockout (OX-/-) mice and double orexin receptor knockout (OX1R-/-;OX2R-/-) mice as narcoleptic models. Central administration of YNT-185 in light period increased wakefulness for 3 hours in wild type (WT) mice but not in OX1R-/-;OX2R-/- mice. Peripheral administration of YNT185 also showed the same effect, which indicates that YNT-185 can pass through the blood brain barrier. Next, we administered YNT185 to OX-/- mice and OX1R-/-;OX2R-/- mice in dark period. Both central and peripheral administration of YNT-185 prevented cataplexy in OX-/- mice; however, the effect was not seen in OX1R-/-;OX2R-/- mice. Fragmented sleep was not improved by administration of YNT185. These results indicate that OX2R-selective agonists have potential as mechanistic therapeutic agents for narcolepsy-cataplexy.

242 P-24

Orexin B exerts an indirect, slow inhibitory action on noradrenergic neurons in the locus coeruleus

Toshiya Yonezawa1, Junya Fukuoka1, Takeshi Kanda1, and Masashi Yanagisawa1,2

1International Institute for Integrative Sleep Medicine, University of Tsukuba 2Departments of Molecular Genetics, University of Texas Southwestern Medical Center

Sleep and wakefulness is regulated by a variety of neuromodulators such as monoamines and peptides in the brain. In the regulation of arousal, lateral hypothalamic orexin neurons are inextricably intertwined with the noradrenergic neurons in the locus coeruleus (LC). Orexin neurons release the neuropeptide orexins A and B. Orexin A binds with high affi nity to both orexin type-1 (OX1R) and type-2 receptors (OX2R), whereas orexin B has a preferential affi nity for OX2R. In the LC, OX1R mRNA has been detected in the noradrenergic neurons, whereas OX2R mRNA in GABAergic neurons. While orexin A rapidly excites LC noradrenergic neurons, the action of orexin B on the LC has not been fully explored. Here we report a novel inhibitory action of orexin B on the noradrenergic neurons. Application of orexin B signifi cantly, and very slowly, reduced spontaneous fi ring of the noradrenergic neurons, which was mediated by GABAAR and OX2R. GABA can induce two components of inhibition, called phasic and tonic. Phasic inhibition is induced by vesicular release of GABA and generates shor t-ter m inhibition, inhibitor y post-synaptic cur rents (IPSCs), while tonic inhibition is induced by ambient GABA and generates long-term inhibition. Unexpectedly, both amplitude and frequency of spontaneous IPSCs in noradrenergic neurons were slightly decreased rather than increased by orexin B. However, GABAAR-mediated tonic currents in LC noradrenergic neurons were enhanced after application of orexin B. These results suggest that orexin B causes tonic, but not phasic, inhibition of LC noradrenergic neurons through activation of OX2R, thereby contributing to the optimization of noradrenergic neuron fi ring and the control of wakefulness.

243 P-25

Two-photon calcium imaging of the cerebral cortex in naturally sleeping and awake mice

Ryo Ishii1, Natsuko Tsujino1, Takeshi Kanda1, Masashi Yanagisawa1,2

1International Institute for Integrative Sleep Medicine, University of Tsukuba 2University of Texas Southwestern Medical Center

Sleep is necessary in mammalian brains, however, even at present, neurobiological properties of sleep are not fully understood. An important aspect of sleep is that sleep exerts profound modulatory effects on the cortex. Toward exploring the nature of sleep, it has been of primary interest over the decades to precisely understand the activity of cortical cells depending on sleep and wakefulness. Using in vivo Ca2+ imaging and transgenic labelling, we visualized activity of identifi ed neurons in the primary motor cortex (M1) of naturally awake and sleeping mice. To identify neuron types in vivo, Vgat-ires-Cre mice, in which Cre recombinase is expressed in GABAergic neurons, were crossed with tdTomato reporter mice (ROSA-CAG-loxP-stop-loxP-tdTomato mice). Histological studies showed that, in the M1 of Vgat-tdTomato mice, all tdTomato-expressing neurons were GABAergic. For optical recording of neural activity, adeno-associated virus encoding GCaMP5G was injected into the M1. GCaMP5G was expressed only in neurons. Thus, GCaMP5G only-expressing and tdTomato/GCaMP5G-expressing cells were identifi ed as excitatory and inhibitory neurons, respectively. After the injection of AAV, a head plate for head fi xation and electrodes for recording of electroencephalogram (EEG)/electromyogram (EMG) were implanted on the mice. The mice were acclimated to running and sleeping on a trackball under head-fi xed conditions. Two-photon microscopy was used to monitor fl uorescence of GCaMP5G and tdTomato in the M1. Excitatory and inhibitory neurons showed distinct activity patterns during periods of wakefulness, non-rapid eye movement (NREM) sleep and REM sleep. These results suggest that spontaneous activities of cortical neurons are regulated by distinct regulatory mechanisms that depend on the neuron type.

244 P-26

The role of Elovl6 in bone and cartilage

Manami Kikuchi1, Masako Shimada1,2, Takashi Matsuzaka1, Kiyoaki Ishii1, Yoshimi Nakagawa1, and Hitoshi Shimano1

1Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba 2Department of Food Science and Nutrition, Sagami Women’s University

Elovl6 (elongation of very long-chain fatty acids family member 6) is microsomal enzyme that regulates the elongation of C12-16 saturated and monounsaturated fatty acids. We have previously shown that Elovl6 plays a critical role in the development of obesity-induced insulin resistance, NASH, and atherosclerosis via the modifi cation of the fatty acid composition. However, the role of Elovl6 in bone and cartilage is unclear. In this study, we investigated the role of Elovl6 in bone and cartilage during developmental stage. Firstly, we analyzed the fatty acids composition of cartilage. Elovl6 defi cient mice showed increased palmitate (C16:0) and decreased stearate (C18:0) as compared to wild type (WT) mice. Next, we analyzed the bone phenotype of Elovl6 defi cient mice. Newborn Elovl6 defi cient mice showed growth retardation and small body compared with WT mice. In the growth plate of tibia, the proliferating zone was shorter, and the hypertrophic zone was longer in Elovl6 defi cient mice than those of WT mice. In order to clarify the reason of this growth plate change, we investigated proliferation, apoptosis, and differentiation of chondrocytes. We found that proliferation of chondrocytes was decreased in growth plate of Elovl6 defi cient mice. There was no difference in apoptosis. Furthermore, the expression of Collagen X a1, the differentiation marker of hypertrophic chondrocytes, was increased in primary chondrocytes of Elovl6 defi cient mice. The expression of FoxA2, which regulates the expression of Collagen X a1, was also increased in Elovl6 defi cient mice. These results suggest that Elovl6 plays an important role in the development of growth plate at least till after birth.

245 P-27

Deletion of Elovl6 protects against the onset and progression of type 2 diabetes in db/db mice

Hui Zhao, Takashi Matsuzaka, Yuta Nakano, Nie Tang, Naoya Yahagi, Yoshimi Nakagawa, Hitoshi Shimano

Department of Internal Medicine (Endocrinology and Metabolism) Faculty of Medicine, University of Tsukuba

Elongation of very long chain fatty acids (Elovl6) is a microsomal enzyme which catalyzes the elongation of C12-16 saturated and monounsaturated fatty acids. We have shown previously that Elovl6 is a major target for sterol regulatory element binding proteins and that it plays a critical role in development of obesity-induced insulin resistance by modifying FA composition. To further investigate role of Elovl6 in development of type 2 diabetes (T2D) and its underlying mechanism, we investigated the effects of Elovl6 deletion in leptin receptor- defi cient db/db mice, a model of T2D. We analyzed body weights, serum glucose, insulin and HbA1c levels of db+/m, db/db, and db/db-Elovl6KO mice. We also performed immunohistochemical staining and quantitative RT-PCR analysis of islet. Although the obesity of db/db-Elovl6KO mice was similar to db/ db mice, development of hyperglycemia and glucose intolerance was dramatically improved. Histological examination indicated that Elovl6 deletion was associated with increased islet and β-cell mass in db/db mice, and this correlated with serum hyperinsulinemia and glucose- responsive insulin secretion. The expression of genes related to pancreatic β-cell function such as PDX-1, MafA, and insulin were increased and the expression of infl ammatory genes such as TNF-α and MCP-1 were reduced in islets from db/db-Elovl6KO mice compared with db/db mice. These results suggest that Elovl6 is an important regulator on both mass and function of β-cell in T2D. Elovl6 inhibition can be a novel therapeutic target for T2D.

246 P-28

The role of CREBH in the small intestine

Fusaka Oikawa, Kana Orihara, Takuya Kikuchi, Yoshimi Nakagawa, Hitoshi Shimano

Department of Internal Medicine, Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba

Metabolic syndrome is caused by the dysfunctions of genes related to energy homeostasis including glucose, triglyceride, cholesterol, etc. CREBH (Cyclic AMP Responsive Element Binding Protein H) is the membrane-bound transcription factor. CREBH mRNA is selectively expressed in the liver and the small intestine. Hepatic CREBH controls fi broblast growth factor 21 expression and its plasma level, which contributes to the catabolic effects on systemic energy homeostasis in the whole body. Therefore, hepatic CREBH is a therapeutic target for obesity and diabetes. However, the role of CREBH in the small intestine remains unclear. We generated intestinal CREBH transgenic (Tg) and CREBH Knockout (KO) mice. Based on both in situ hybridization and Real-Time PCR analysis, CREBH mRNA was mainly expressed in epithelium cells of the small intestine. The histopathological analysis staining with hematoxylin and eosin (H&E) demonstrated that the villus in Tg mice was longer, whereas it was shorter in KO mice than that of WT mice. To determine the effects of CREBH on cell proliferation, the small intestines were stained with anti-PCNA antibody. PCNA-positive cells were increased in Tg mice and decreased in KO mice compared with WT mice. Moreover, we assessed the speed of cell proliferation in the small intestine using BrdU assay. BrdU positive cells were increased in Tg mice compared with WT mice. Reversely, it was decreased in KO mice compared with WT mice. CREBH might enhance the cell proliferation, resulting in the elongation of the villus length in the small intestine. Although the villus length depends on the cell proliferation in crypt, CREBH expression is localized in epithelium cells of villus, but not in crypt. Therefore, we speculate that CREBH would induce a secretary factor in villus, which enhances the cell proliferation of crypt in a paracrine manner.

247 P-29

Hereditary thrombocytosis with a germline mutation in the kinase domain of JAK

Koichiro Maie, Yasuhisa Yokoyama, Takayasu Kato, Hidekazu Nishikii, Naoki Kurita, Hideharu Muto, Naoshi Obara, Yuichi Hasegawa, Mamiko Sakata-Yanagimoto, Shigeru Chiba

Department of Hematology, University of Tsukuba

The somatic mutation in the Janus kinase 2 (JAK2) gene, V617, is a hallmark of myeloproliferative neoplasms, such as polycythemia vera, essential thrombocytosis (ET), and primary myelofi brosis. In ET patients, half the cases have V617F JAK2 mutation, followed by those having mutations in calreticulin and MPL at 30-40% and 5-10%, respectively. On the other hand, in hereditary thrombocytosis, germline mutations have been identifi ed mostly in MPL and TPO genes, while only a small number of families are reported to have germline JAK2 mutations. Interestingly, despite the high prevalence of JAK2 V617F mutation in sporadic ET cases, no families have been reported to carry this mutation in the germline. To our knowledge, JAK2 germline mutations reported so far are R564Q, V617I, and S755R in the pseudokinase domain, and R867Q and R938Q in the kinase domain. Here, we describe a Japanese family with hereditary thrombocytosis. The TPO, MPL and JAK2 genes were examined by direct sequence of genomic DNA of mononuclear cells separated from peripheral blood. We identifi ed JAK2 R867Q mutation in all the affected subjects. The mutation was heterozygous and found also in the buccal swab. In contrast, none of the unaffected subjects in this family had JAK2 R867Q mutation. These results indicate that we found the fi rst family in the Japanese population having the JAK2 R867Q germline mutation causing hereditary thrombocytosis and that this mutation causes thrombocytosis in an autosomal dominant manner probably at 100% penetrance.

248 P-30

Notch signaling pathway of nestin-expressing cells in bone marrow

Tatsuhiro Sakamoto1, Naoshi Obara2, Ryosuke Fujimura3, Takayasu Kato2, Cao Sy Luan1, Shigeru Chiba2

1Hematology, Graduate School of Comprehensive Human Sciences, University of Tsukuba 2Department of Hematology, Faculty of Medicine, University of Tsukuba 3School of Medical science, University of Tsukuba

Non-hematopoietic cells in bone marrow form hematopoietic stem cell niche and these are important for hematopoiesis and the maintenance of hematopoietic stem cell. Nestin- expressing cells in bone marrow are reported as one part of hematopoietic stem cell niche. However, the mechanism how nestin-expressing cells affect hematopoiesis remains unclear. On the other hand, it is well known that the notch signaling pathway of nestin-expressing cells is important for neurogenesis. According to this fact, we hypothesize the notch signaling pathway in nestin-expressing cells is also important for hematopoiesis. Therefore, to confi rm our hypothesis, we generated a conditional knockout mice (CKO mice) model that carried a tamoxifen-inducible deletion of rbpj specifi cally in nestin-expressing cells (nestin-creERT2; RBPJ fl ox/fl ox mice). RBPJ is the transcription factor in notch signaling pathway and it is indispensable for this pathway. By FACS analysis, after 8 weeks tamoxifen administration, mature erythroid cells (CD71+Ter119+ cells) are decreased in bone marrow of CKO mice, compared with wild-type mice (22.3% vs 49.8% of other linage negative cells, p<0.001). And immature erythroid cells (CD71+Ter119- cells) are increased in CKO mice (12.3% of other linage negative cells) than wild-type mice (5.3% of this fraction) (p=0.004). Myeloid progenitor cells are similar between wild-type mice and CKO mice. CKO mice developed mild splenomegaly (225 mg) compared with wild-type mice (139 mg) (p=0.001). From this data, abnormal differentiation of erythroid seems to be occurred in bone marrow of CKO mice. Notch signaling pathway in nestin-expressing cells in bone marrow does not affect myeloid cells and it may be important for the differentiation of erythroid.

249 P-31

Ceramide/Ceramide-1-phosphate balance and the cisplatin- induced apoptosis of cochlear hair cells

Quang Le, Keiji Tabuchi, Akira Hara

Department of Otolaryngology, Faculty of Medicine, University of Tsukuba

[Background] Identifi cation of effector molecules involving in the regulation of cell fate is crucial to develop a proper therapeutic strategy. In cochlear-hair-cell death induced by cisplatin, one of identifi ed decisive factor is elevation of ceramide which is derived from activation of sphingomyelinase. Ceramide-1-phosphate (C1P) is a phosphorylated form of ceramide. The phosphorylation of ceramide is mediated by ceramide kinase. While ceramide is an inducer of apoptosis of hair cells in cisplatin ototoxicity, little is known about the function of C1P in the cochlear diseases. [Purpose] The present study was designed to show whether C1P could affect cisplatin-induced apoptosis of cochlear hair cells. [Materials and Methods] Explants of cochlear basal turns collected from C57BL/6J mice at postnatal day 3 to 5 were used in all experiments. Cochlear explants were exposed to 10 or 5 μM cisplatin for 48 hours to assess the effects of C1P or NVP-231 (a ceramide kinase inhibitor). Western blotting of Akt/pAkt was conducted to check whether this pathway was modulated by C1P. [Results] C1P activated the Akt pathway and signifi cantly reduced cochlear cell death induced by cisplatin. In addition, when treating cochlear hair cells with NVP-231 under the present of cisplatin, a remarkable increase in apoptosis of hair cells was recognized. [Conclusion] The present fi ndings confi rmed the anti-apoptotic function of C1P in the cisplatin ototoxicity. The balance between ceramide and C1P may play a critical role in determination of hair cell fate in cisplatin ototoxicity.

250 P-32

Molecular basis of microglial properties regulated by culture condition

Tomomi Okajima1, Fuminori Tsuruta2, Tomoki Chiba2

1The College of Biological Sciences, School of Life and Environmental Sciences, University of Tsukuba 2Graduate School of Life and Environmental Sciences, University of Tsukuba

Microglia are crucial for the regulation of immune response and homeostasis in the central nervous system. Under normal condition, microglia extend and retract their ramifi ed processes to monitor the brain environment. When microglia sense a pathological condition, their morphologies were altered from ramifi ed to amoeboid forms. Thus, it is considered that microglia morphology is related to the regulation of both microglial status and physiological function. However, the mechanisms that underlie the regulation of microglial morphology remain to be elucidated. In this study, we explored the regulatory factors that determine the microglial morphology. To explore these regulatory factors, we fi rst observed morphology of microglia cell lines, BV2, cultured in a variety of media. In consequence, we found that microglial morphology was changed when cells were cultured in high nutrient medium. In addition to BV2 cells, the mouse primary microglia were also infl uenced by this culture condition. Taken together, these data suggest that these regulatory factors were contained in high nutrient medium.

251 P-33

Neuroendocrine control of mating-induced female germline stem cell proliferation in the fruit fl y Drosophila melanogaster

Tomotsune Ameku1 and Ryusuke Niwa1,2

1Graduate School of Life and Environmental Sciences, University of Tsukuba 2PRESTO, JST, Japan

Gametogenesis and mating are two essential components of animal reproduction. Gametogenesis is modulated by the need for gametes, yet little is known of how mating, a process that consumes gametes, may modulate the process of gametogenesis. Here, we show a relationship between mating stimulus and female germline stem cell (GSC) proliferation through neuroendocrine system in the fruit fl y Drosophila melanogaster. We found that mating stimulated an increase in GSC number. We also found that the level of the principal insect steroid hormone called ecdysteroid in the adult ovary was signifi cantly elevated after mating. To examine whether the mating-induced ovarian ecdysteroid biosynthesis is crucial for inducing GSC proliferation, we established adult ovary-specifi c RNAi animals for neverland (nvd), which encodes the ecdysteroidogenic enzyme responsible for converting dietary cholesterol into 7-dehydrocholesterol (7dC). nvd RNAi animals did not exhibit a mating-induced increase in female GSC number. In addition, the GSC phenotype was rescued by an oral administration of 7dC or 20-hydroxyecdysone (20E). Moreover, a mating-induced GSC proliferation was regulated by the male seminal fl uid peptide called a Sex peptide (SP) and its receptor SPR, the important signaling pathway that transduces mating stimulus to a specifi c subset of female neurons. SPR RNAi female fl ies did not show a mating-induced increase in either ovarian ecdysteroid level or female GSC number. Importantly, the GSC phenotype in SPR RNAi animals was rescued by an oral administration of 20E. All of our data suggest that a mating-induced increase in female GSC number is regulated by the ovarian ecdysteroid whose biosynthesis is positively controlled by neuronal SP-SPR signaling in mated female fl ies. This is the fi rst study to show that GSC proliferation is under the control of the characterized neuroendocrine system in response to external stimulus, mating.

252 P-34

Glutathione biosynthesis is essential for larval development in the fruit fl y Drosophila melanogaster

Chikana Yamamoto1, Sora Enya1, and Ryusuke Niwa1,2

1Graduate School of Life and Environment Science, University of Tsukuba 2PRESTO, JST

Steroid hormone is a physiologically-active substance that plays an important role for development, sexual maturation and maintenance of homeostasis in multicellular organisms, including humans. In insects, the major steroid hormones called ecdysteroid, including ecdysone and its derivative 20-hydroxyecdysone (20E), play pivotal roles in regulating a number of events, especially molting and metamorphosis. In the last decade, enzymes responsible for converting the precursor cholesterol to the active ecdysteroids have been identifi ed and characterized. One of the biosynthesis enzymes is Noppera-bo (Nobo) that involved in regulating a transport and/or metabolism of intercellular cholesterol in the ecdysteroidogenic organs (Enya S et al. Sci. Rep., 4:6586, 2014). Nobo belongs to the family of glutathione S-transferases (GSTs), which catalyzes the conjunction of the reduced form of glutathione (GSH), essential tripeptide composed of glutamic acid, cysteine and glycine to the substrate. Since GSH is de novo synthesized in vivo, it is easily expected that GSH biosynthesis is crucial for ecdysteroid biosynthesis. However, the role of GSH biosynthesis has not yet been elucidated in insects. We therefore aimed to elucidate the role of GSH biosynthesis during the development, especially ecdysteroid biosynthesis, in the fruit fl y Drosophila melanogaster. We generated genetic null mutant of the gene called γ-glutamylcysteine synthetase (Gclc), which encodes a catalytic component of enzyme conjugating glutamic acid and cysteine in the GSH biosynthesis pathway. We found that gclc mutant was lethal at the 2nd instar larva stage. This phenotype was rescued by feeding of 20E, and gclc mutant animals grew further to the 3rd instar larvae. These results suggest that, as we expected, GSH biosynthesis is required for ecdysteroid biosynthesis. Further detailed analyses on gclc mutants will be presented.

253 P-35

The effect of the parasitic wasp Asobara japonica on the development of its host, the fruit fl y Drosophila melanogaster

Hitomi Takemata1, Yuko Shimada-Niwa2, and Ryusuke Niwa1,3

1Graduate School of Life and Environmental Science, University of Tsukuba 2Life Science Center of Tsukuba Advanced Research Alliance, University of Tsukuba 3PRESTO, JST, Japan

The fruit fl ies belonging to the genus Drosophila, especially D. melanogaster are recognized as the most excellent and convenient model organisms for many aspects of biological studies. In laboratories, Drosophila fl ies are usually cultured without any deleterious parasites. In the wild, in contrast, as much as 90% of Drosophila fl ies are infected with a variety of parasitoid wasps. Thus, elucidating how parasitoid wasps affect Drosophila development and physiology would shed light on unexpected potentials and unraveled mechanisms of the fruit fl ies, which are inaccessible in the regular laboratory research conditions. To address this issue, we have examined how infection with the parasitoid wasp Asobara japonica affects the D. melanogaster development. A. japonica is generally parasitic in Drosophila species. The adult wasp sticks its needle to a fl y larva for laying wasp eggs into the larva. Eggs develop in a fl y larva and eventually a single adult wasp emerges from a single fl y pupa. We found that the A. japonica infection impaired development and growth of D. melanogaster imaginal discs, the adult organ precursors. On the other hand, the A. japonica infection did not severely affect development and morphology of the brain and the steroid hormone-biosynthesizing organ, both of which are required for D. melanogaster development and survival. These observations raise a possibility that a wasp somehow distinguishes D. melanogaster organs/tissues that should be retained from ones that should be degenerated for the wasp development, which might be a process to deprive the fl y of nutrients for the growth of wasps. Currently, we are focusing on these interesting phenomena, and studying molecular mechanisms that cause these events. Further data will be presented and discussed.

254 P-36

Risk Factor Analysis of Diabetes in Fiji; a Comparison of the Findings from the WHO STEPS survey in 2002 and 2011

Drauna Adi Miriama Naioba Drauna1, Ma Enbo2, Wagatsuma Yukiko2

1Graduate School of Comprehensive Human Sciences, University of Tsukuba 2Department of Clinical Trial and Clinical Epidemiology, Faculty of Medicine, University of Tsukuba

Background: Despite it being a disease that can be prevented and controlled through lifestyle as other non-communicable diseases, the incidence of diabetes is at a steady increase and the World Health Organization (WHO) projects that diabetes will be the 7th leading cause of death in the world by 2030. To date, more than 80% of diabetes deaths occur in low and middle income countries especially in the urbanized population, and the small island nation of Fiji is no exception. Findings from the WHO statistics 2011 show that diabetes deaths in Fiji reached 219, accounting for 5 % of total deaths. The age-adjusted death rate was 41 per 100,000 which ranked 79th in the world. According to the International Diabetes Federation (2012), 1 in every 4 to 5 people in Fiji is affected by the disease. However, more recent statistics by the Ministry of Health in Fiji dictates that this has worsened to 1 in every 3 Fijians. Moreover, the WHO formulated a tool for its member countries which allows for non-communicable disease risk factor surveillance known as the WHO NCDs STEP survey, which Fiji utilized for the fi rst time in 2002 and then again in 2011. Objective: To identify and compare the characteristics of diabetes prevalence in Fiji in 2002 and 2011 Methodology: A complex survey data analysis of the datasets is being underway. The characteristics of the prevalence of diabetes for each year will be looked at, namely age group, sex, ethnicity, education level and location. This may be descriptively compared between the two survey years. Furthermore, the relationship of the prevalence of diabetes with the risk factors of interest may be analyzed through multiple regression analysis. Results: The report has indicated a diabetes prevalence of 16% in the country. The rate for Fijians of Indian descent was 21%, almost doubling that of Indigenous Fijians (11%). There was a signifi cantly higher proportion of diabetes in the urban-dwellers (25%) than rural dwellers (13%). Diabetes prevalence was higher in females and increased with age. Conclusion: Diabetes continues to be a problem of great public health concern in the country, just as it had been declared in 1970.

255 P-37

Impact on the mother of the preparation to children receiving proton therapy

Noriko Ozawa1,2, Kayuri Furuya1

1Child Health Nursing, Faculty of Medicine Sciences, University of Tsukuba 2University of Tsukuba Hospital

Proton therapy is one of the radiation treatments in pediatric cancer treatment. Proton therapy is expected to reduce the late complications. Often anesthesia is used in radiation therapy. However, by carrying out the preparation of the children, has been shown that it is possible to reduce the amount of anesthetic. The purpose of preparation promotes the preparation of children’s mind, it is to draw the child’s ability to cope. Preparation is often carried out with the cooperation mother is the main attendant’s. So, this study revealed mother’s impact of participate in the preparation from interview to fi ve of the mother. When actual treatment begins and child is suffering to receive treatment, that mothers embrace the ethical dilemma is often characterized. In addition, proton therapy facility is few, it is often require changing hospital for treatment. So there were many that mothers feel a sense of confusion in the relationship with the new medical staff. However, when mothers thought that the use of anesthesia has been premise, they received an explanation about the intervention of preparation, they had been able to think that they have thing to give children. In addition, mothers knew that medical staff is caring children’s feeling, it was connected to the sense of security to the medical staff. And mothers could think that I was able to achieve a proton beam therapy with children through preparation. From these, preparation is carried together with the parent, not only impact on the children, can infer that there are a variety of effects to the parent, the importance of the preparation was suggested.

256 P-38

Analysis of center-of-gravity variation on bed for fall prediction

Daichi Araki1, Takayasu Kawaguchi2

1Nursing Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba 2Environmental Health Nursing, Faculty of Medicine, University of Tsukuba

Falling from the bed is a common type of accident and places considerable burdens on patients and nurses. Structural and risk factors for the occurrence of falls have been identifi ed, but fall prevention remains extremely diffi cult due to the patient’s physical, mental, and social factors and treatment environment. Most fall prevention measures involve ascertaining the risk of falls through the use of risk assessment score sheets and bed sensors, but there are few measures for active fall prediction. To develop a method for fall prediction, we applied area trajectory analysis, spectrum analysis, chaotic analysis, and detrended fl uctuation analysis to the characteristics of center-of-gravity variation in certain positions and movements. We used these analysis methods to calculate periphery area, spectral density, Lyapunov exponents, and fl uctuation indices (α1, α2). Experiments were performed with 6 healthy male and female participants aged ≥ 18 years. Each participant maintained 10 positions or movements on a bed for 1 min each, during which time-series data on center-of-gravity variation were recorded. The longitudinal and latitudinal directions of the bed were taken as the x- and y-axes, respectively. Compared with other movements or positions, repeated shaking in the supine position exhibited signifi cantly larger variation on the x- and y-axes for the spectral density, Lyapunov exponent, and fl uctuation indices (α1, α2). Displacements along the x- and y-axes tended to be larger in the sitting position than in other positions. The results of this study suggest the possibility of fall prediction through center-of-gravity analysis.

257 P-39

Changes in Nursing Practice by Using Cognitive Behavioral Therapy

Chisato Yamazaki1, Yoshie Okada2

1Master’s Program in Mental Health Nursing, University of Tsukuba 2Faculty of Medicine, University of Tsukuba

The objective of this study was to reveal how the practice of nursing changed in nurses who had been using cognitive behavioral therapy (CBT) since they learned this method. A questionnaire survey was performed in 500 nurses, and answers were obtained from 141 nurses (the response rate 32%). Of these, 70 nurses (50%) had been using CBT after their training. The most remarkable change was “the ability to realize the tendency of patients’ cognition and to know how to deal with it” as responded by 56 nurses (78.9%), followed by “feeling the effects of care” and “feeling pleasure in nursing practice” as reported by more than a half of the respondents. Thus, it was suggested that they had acquired the cognitive intervention skills after the training and that their use of CBT might have led to the feelings of care effects and pleasure in nursing practice.

258 (Public Health (Public and Nursing Session) 22

Monday, September 28 Building Research CapacityBuilding Global in Health: and Challenges Opportunities Venue: Conference Room 406 Building Research Capacity in Global Health: Opportunities and Challenges (Public Health and Nursing Session)

Well-designed scientifi c research helps us fi nd effective solutions to global health challenges, yet building research capacity in low and middle-income countries is lagging behind. This session aims to share research experiences in those countries and to discuss the role we can play to enhance their research capacity.

Session Organizers: Masao Ichikawa and Yoshie Okada Chair: Yoshie Okada, University of Tsukuba Masao Ichikawa University of Tsukuba 14:15-14:30 Introduction Tonda Hughes University of Illinois at Chicago 14:30-15:15 Global Nursing Partnerships to Address Local Health Problems: Building Educational and Research Capacity in Low and Middle-Income Countries Chang-Chuan Chan National Taiwan University 15:15-16:00 Air Pollution and Public Health Impact in Ulaanbaatar, Mongolia 16:00-16:30 Coffee/Tea and Free Discussion Masao Ichikawa, Tonda Hughes, Chang-Chuan Chan 16:30-17:15 Interactive Session

259 22-1

Global Nursing Partnerships to Address Local Health Problems: Building Educational and Research Capacity in Low and Middle-Income Countries

Tonda L. Hughes, PhD, RN, FAAN

Professor and Associate Dean for Global Health University of Illinois at Chicago, College of Nursing, Chicago Illinois, USA

Opportunities for nurses to improve global health have never been as plentiful as they are today, especially in low and middle income countries (LMICs) where the double burden of infectious and non-communicable diseases is greatest. Clinical and other health- related research is a key strategy to improving health outcomes of individuals, families and communities in LMICs. However, despite that fact that developing countries bear 90% of the global disease burden, only 10% of all health research funding is used to address diseases that most affect the people in these countries—a situation described as the “90-10” gap by the Global Forum for Health Research. Nurses can play a key role in building research capacity in LMICs, thereby helping to close this gap.

In this presentation I will describe several examples of international collaborations between the University of Illinois at Chicago, College of Nursing and schools of nursing in LMICs that are aimed at building nursing education and/or research capacity. Examples of these include (1) an 11-year collaboration with Bel-Air hospital in Panchgani, India in which we helped develop a bachelor’s degree in nursing program, and more recently a master’s degree program with a specialty in HIV/AIDS; (2) a research capacity development project at Kamuzu College of Nursing in Malawi that has resulted in a number of nursing faculty earning PhDs, as well as multiple research publications; and (3) participation in the 7-year Rwanda Human Resources for Health project that aims to rebuild the health education and healthcare infrastructure following the 1994 genocide which resulted in nearly a million deaths in that country.

260 22-2

Air Pollution and Public Health Impact in Ulaanbaatar, Mongolia

Munkh-Erdene Luvsana,b, Yu-Kai Huanga, Yi-Ting Chena, Joe-Chi Wua, Enkhjargal Gombojavc, Chimedsuren Ochirc, Jargal Bulganc,d, Chang-Chuan Chana,e*

aInstitute of Occupational Medicine and Industrial Hygiene College of Public Health, National Taiwan University bDepartment of Health Policy and Management, School of Public Health Health Sciences University of Mongolia cSchool of Public Health, Health Sciences University of Mongolia dCustom’s Professional Inspection Offi ce of Buyant-Ukhaa port, Mongolia eGlobal Health Center, College of Public Health, National Taiwan University

The growth in traffi c, demand for electricity and heating in a rapidly urbanized and industrialized Mongolia, especially the capital city of Ulaanbaatar, has led to a severe air pollution in recent years. A mutually-funded cooperative research between Taiwan (National Taiwan University) and Mongolia (Health Science University of Mongolia) has been carried out to assess public health impact by the ever increasing air pollution during 2011-2013. Our study method included compiling historical air quality data and health data in Mongolia as well as performing air quality measurements, and questionnaire survey and bio-monitoring for 320 children aged 11 to 15 years living in gers, brick houses and apartments, in ger and non-ger areas of Ulaanbaatar. Our study found the need for heating in Ger areas in cold season was a main cause of elevated SO2 and NO2 concentrations, while emissions from traffi c and coal- fi red power plants in warm seasons were additional sources of air pollution in Ulaanbaatar. Mongolian children’s urinary levels of heavy metals and 1-OHP were signifi cantly elevated during the cold season, and for those living in ger areas, gers, or brick houses in Ulaanbaatar. Children’s urinary levels of air pollutants were associated with emissions from coal, traffi c with indoor emissions from stoves in some households. This successful cooperation produced three Taiwanese masters and one Mongolian PhD majoring in public health at National Taiwan University. Our research fi ndings provided evidence to Mongolian governments for policy formation and actions to alleviate air pollution and protect public health.

261 NOTE

262 23 The 3rd International Conference on Global Aging

Wednesday, September 30 Venue: Conference Room 406/303

The 3rd International Conference on Global Aging

The United Nations Population Fund disclosed in 2012 that 80% of the 1.5 billion older people in the world would live in developing countries by 2050, thus aging is an urgent, global-scale issue. In this conference on Global Aging, we aim to share our ideas and fruits of researches on old-age issues through medical, nursing, care, social, and cultural points of view; as well as advocate policies on aging for each country.

Session Organizers: Nanako Tamiya, Shiho Kashiwagi

Venue: Conference Room 406 Chair: Felipe Alfonso Sandoval Garrido, Part One Waseda University, CGAT Sandra Moody Levin Kameda Medical Center & University of California 13:40-14:00 Palliative Care for Older Adults Mayer Thomas Faculty of Medicine, UT 14:00-14:15 Guidelines for clinically assisted nutrition and hydration in the context of treatment and care at the end of life in the United Kingdom Tamaki Saito Faculty of Medicine, UT 14:15-14:30 Support needs assessment of aging parents who live with Hikikomori children Venue: Conference Room 303 Chair: Ichiro Kai Part Two Visiting Prof. CGAT ; Prof. Emeritus Tokyo Univ. Chair, The Japan Gerontological Society Tomoko Wakui Tokyo Metropolitan Institute of Gerontology 14:38-14:44 Families’ readiness for end-of-life care of older adults with care needs Jin Xueying Doctoral Program in Human-Care Science, UT 14:44-14:50 Falls in Long-Term Care Health Facilities for elderly: Do time, day and season matter? Kumi Watanabe Master’s Program in Medical Science, UT 14:50-14:56 Social relationships and mortality: Which aspects of social relationships impact the maintenance of function in the elderly? Yoko Kobayashi Tsukuba University of Technology 14:56-15:02 Activity limitation, social and health conditions among Japanese elderly people with hearing loss Chair: Tomoko Wakui Part Three Tokyo Metropolitan Institute of Gerontology Yoko Moriyama National Institute of Public Health Impact of respite care on speed until admission to 3 types of facility of the 15:02-15:08 elderly certifi ed as eligible for long-term care insurance in Japan: From Survey of Long-term Care Benefi t Expenditures

263 Hiroaki Ueshima Faculty of Medicine, UT 15:08-15:14 A descriptive study of the length of stay at home in days for long-term-care insurance users with severe disability in a prefecture of Japan Masamitsu Mikoshiba Graduate School of Comprehensive Human sciences, UT 15:14-15:20 Five-year transition patterns of care-need level Akira Kawamura Faculty of Medicine, UT The trial of the shift from tubal to oral feeding in long-term care facilities: a 15:20-15:26 descriptive analysis of the difference among Care-Levels, facility types and prefectures in Japan Hideto Takahashi Fukushima Medical University 15:26-15:32 How do we share confi dentiality sensitive information in large study group? Chair: Yui Yamaoka Part Four Faculty of Medicine, UT Masatoshi Uchida Faculty of Medicine, UT 15:32-15:38 Abdominal pain in oldest-old emergency patients Yuki Imamura Master’s Program in Medical Science, UT 15:38-15:44 MafB impairs tumor growth through decrease of tumor-associated macrophages Demonstration 15:44-15:50 Health Care Robots demonstration AIST Chair: Makiko Kawabe Part Five Social Security research Group, Mitsubishi Research Instetute.Inc Kaori Kishi Doctoral Program in Human-Care Science, UT 15:50-15:56 Psychosocial and criminological factors related to recidivism among Japanese criminals at offender rehabilitation facilities Takafumi Monma Doctoral Program in Human-Care Science, UT 15:56-16:02 The effects of sense of coherence on mental health among community- dwelling older adults Sakiko Ozawa Doctoral Program in Human-Care Science, UT 16:02-16:08 Age differences in psychosocial factors of work engagement among company employees Nick Warren Department of Psychology, University of Utah 16:08-16:14 Perceptions of aging and disability among college students in Japan Chair: Makiko Kawabe Part Six Social Security research Group, Mitsubishi Research Instetute.Inc Keishi Ebisawa Comprehensive Human Sciences (credited auditors), UT 16:14-16:20 A comparative study of community-based welfare system in Japan and China Graduate School of Systems and Sekpon Bakumyna Information Engineering, UT 16:20-16:26 Population aging and social issues in West Africa: A comparative analysis of Benin and Japan

264 Josephine Laker Master’s Program in Medical Sciences, UT 16:26-16:32 Literature review on the relationship between social network and quality of life of older people in African countries Reiko Hoda Kansai University of Welfare Sciences 16:32-16:38 Comparison of population trends of new immigrants in Japan and Finland: a literature review Felipe Sandoval Waseda University and CGAT 16:38-16:44 The Relation between informal care provision and major depressive disorder among rural elderly people in South Africa

265 23-1

Palliative Care for Older Adults

Sandra Moody

Professor-in-Residence, Department of Post-Graduate Medical Education, Kameda Medical Center, Kamogawa-shi, Chiba Associate Professor of Clinical Medicine, Department of Medicine, Division of Geriatrics, University of California, San Francisco, California, USA

With medical advances, people are living longer. “As populations age, the pattern of disease that people suffer and die from also changes. Increasingly, more people die as a result of serious chronic disease such as heart disease, cerebrovascular disease (including stroke), respiratory disease and cancer (Davies E and Higginson IJ [eds.], WHO Europe, 2004).” Many older people experience long periods of physical decline, functional impairment, and a wide range of symptoms resulting from their disease(s). Thus, the need for geriatric palliative care is on the rise. Previously, and even currently in many countries, palliative care as specialty medicine was offered only to those with cancer diagnoses. This is changing. Palliative care was also once considered end-of-life or hospice care only, but it is now recognized that palliative care can be provided “at anytime along the trajectory of any life-threatening illness,” even in combination with life-prolonging treatment (Bunch O’Neil L, Morrison RS, UpToDate 2015). Geriatric palliative care is a feasible option for older adults. Good palliative care for older adults, however, is met with challenges. Although the aim of palliative care treatment is the same for all age groups, in older adults compared with younger people, different issues arise. This lecture will discuss how in older adults both pain and non-pain symptoms are undertreated and how issues such as physiological changes that occur with normal aging, diffi culty in estimating prognosis (compared with cancer diagnoses), and the presence of geriatrics syndromes must be considered in the delivery of good palliative care (Morrison RS, J Palliat Med, 2013; Ritchie CS & Zulman DM, J Palliat Med, 2013; Combs S, Kluger BM & Kutner JS, J Palliat Med, 2013).

266 23-2

Guidelines for clinically assisted nutrition and hydration in the context of treatment and care at the end of life in the United Kingdom

Thomas Mayers, Assistant Professor

Medical English Communications Center, Faculty of Medicine, University of Tsukuba

Medical treatment and care for people at the end of their lives is a very important and very complex issue. Recent trends in end of life care in the UK focus on the idea of “choice,” stressing the importance of a person’s wishes and decisions regarding their end of life care. However, decisions regarding medical care and interventions can often be particularly diffi cult towards the end of life, not only for the patients and their families, but also for the doctors. This is especially true for the subject of clinically assisted forms of nutrition and hydration, such as intravenous feeding, percutaneous endoscopic gastrostomy (PEG), radiologically inserted gastrostomy (RIG), etc. While clinically assisted nutrition and hydration is regarded, as a medical intervention in the UK, we also consider the provision of food and water, nutrition and hydration, as being part of basic care for a patient, that meeting our basic physical needs as human beings. Provision of clinically assisted nutrition and hydration, however fundamental they may appear, could also present problems for the patient and may not be in the patient’s best interests. Many factors then must inform any decision to provide or, indeed, withdraw such treatments.In order to promote good medical practice across the UK the General Medical Council provides physicians with detailed guidelines for every aspect of medical practice. Among these guidelines are those that deal specifi cally with good practice for decision-making regarding treatment and care for patients at the end of life. These guidelines include “decision- making models” to help the physician come to the best decision for each individual patient. In this presentation, I will introduce these guidelines and focus upon the issue of clinically assisted nutrition and hydration as an example of UK policy and attitudes surrounding end of life care.

267 23-3

Support needs assessment of aging parents who live with Hikikomori children

Tamaki Saito, Nobuaki Morita, Yasukazu Ogai

Social Psychiatry and Mental Health, Faculty of Medicine, University of Tsukuba

In May,2010, Japanese Cabinet offi ce reported there are about 700,000 adolescent people who are in socially withdrawal state without any psychosis in Japan. This state is commonly called `Hikikomori’. Hikikomori is not diagnosis or clinical entity. It’s a kind of condition which including many non-pathological cases, yet in many cases, social withdrawal states are prolonged for many years. Some studies suggest that aging risk of hikikomori patients and their parents. There has been increasing needs for assessment of aging parents who are living with hikikomori children. We conducted a questionnaire survey of parents’ needs. Method: A 48-item psychosocial risk questionnaire was administered to 133 families of hikikomori children who are members of our family association. This questionnaire measures parents’ attitude to their aging hikikomori children and anxiety on this problem. Results: Average age of parents was 65.5 ,and average age of hikikomori children was 34.4. Average period of withdrawal was 155.4 months. Most common cause of hikikomori was “bullying in school and workplace”(24.0%). The number of parents who doesn’t access any support or treatment was 57(42.9%). 63.2% of parents had anxiety on children’s isolated life after parents’ death. But 33.1% of parents didn’t prepare for leaving will or inheritance. Parents’ average score of K6 depression scale was 12.2. Conclusions: Aging of hikikomori patients and their parents are increasing problem. Many parents are depressive or preparatory depressive state because of stress of caring for hikikomori children, shame about their public image and anxiety on children’s life after parents’ death. Parents of hikikomori have strong needs not only for welfare service but also for basic support for economic stability. For example, making sustainable lifeplan is helpful for parents.

268 23-4

Families’ readiness for end-of-life care of older adults with care needs

Tomoko Wakui1,2, Kaoruko Aita3, Ichiro Kai2,3

1Tokyo Metropolitan Institute of Gerontology 2Tsukuba University 3The University of Tokyo

Place of death is an important component of quality of life towards the end of one’s life. Studies have discussed place of death, how to fulfi ll one’s wishes, and procedures to follow in advanced care planning. In Japan, family is essential in providing care, choosing what services to use, and making decisions about end-of-life care. However, the family’s readiness for end-of-life care has been overlooked. This study identifi ed factors associated with families’ readiness for end-of-life care provision to older adults with care needs. In 2011, we distributed self-administered questionnaires to family caregivers of older Japanese individuals with care needs. The sample included 932 caregivers from 17 municipalities in Fukui Prefecture. Spouses made up 26.5% of the sample; children made up 73.5%. The caregivers’ mean age was 66.5 years. Twenty-one percent of family members reported having prepared for end-of-life care; 15% had discussed end-of-life care with the care recipients. Logistic regression analysis revealed that care recipients’ age, Activity of Daily Living dependency, and better fi nancial situation were signifi cantly more likely to be associated with families’ readiness regarding end-of-life care. Those who had a discussion with older adults were 2.6 times more likely to report prepared, as compared to those without a discussion. Furthermore, having formed an opinion for family members regarding the end-of-life care location was 2.7 times more likely to infl uence the readiness, after controlling for care recipient and caregiver factors, and engagement in a discussion. This research reaffi rmed the importance of discussions between families and care recipients. The study also suggests that having a concrete idea for families about the end of life care location leads to the actual behavior of the preparation. Support for family to commit themselves on where to support older adults would facilitate the fulfi llment of the latter’ wishes at the end of life care.

269 23-5

Falls in Long-Term Care Health Facilities for elderly: Do time, day and season matter?

Xueying Jin1, Nanako Tamiya2, Felipe Sandoval2,3, Sumiko Miyata1

1Department of Health Service Research, Doctoral Program in Human Care Science 2Department of Health Service Research, Facility of Medicine, University of Tsukuba 3Facility of Political science and Economics, Waseda University

Objective: To assess whether falls are infl uenced by specifi c times of the day, days of week or seasons. Method: This study is a retrospective chart review of falls in a long-term care health facilities for elderly (LTCHFE) from 2004 to 2008. Falls were reported using an accident report that included a facility identifi cation code, date, time of day, sex, age, location of the fall syndrome and activity leading to the fall. Comparison of observed frequencies of falls with expected frequencies if there was no seasonal effect was done by the chi-square test. Result: There were 2056 falls during the 5-year observation period. Most falls (67%) occurred in the resident’s room (39%) and dining hall (31%). Most falls occurred when transferring to a wheelchair (60.5%), 22.8% when walking. There were six peaks during which the frequency of falls was higher in a 24-hour period (6:00-6:59, 9:00-9:59, 11:00-11:59, 13:00- 13:59, 16:00-17:59, 19:00-19:59). Of these times, the peaks at 9:00-9:59 and 11:00-11:59 were signifi cantly lower than the other 4 peaks (=22.30, p<0.001). Chi-square analysis revealed that the proportion of falls was not statistically signifi cant with respect to days of the week. (=0.024, p<0.877). A statistically signifi cant higher percentage of falls (27.4%) occurred in winter (compared with expected numbers in every season, p<0.001) and s statistically signifi cant lower percentage of falls (21.1%) occurred in summer. Discussion: Our result shows the signifi cantly different frequency of falls by time of day and season. Fall-prevention strategies should target “peak” periods and seasons to reduce the number of falls. Conclusion: More research is needed to evaluate the possible causes of this temporal pattern of falls in LTCHFE.

270 23-6

Social relationships and mortality: Which aspects of social relationships impact the maintenance of function in the elderly?

Kumi Watanabe, Emiko Tanaka, Cunyeon Kim, Tokie Anme

Empowerment Science; Lifespan Development Laboratory, Faculty of Medicine, University of Tsukuba

With the acceleration of demographic aging, ensuring healthy longevity is an urgent issue worldwide. Consequently, in terms of prevention of aging related problems, social relationships have received substantial attention. Previous studies have demonstrated that social relationships may contribute positively to an elderly person’s function. However, only few studies have examined which aspects of social relationships have the strongest infl uence on these functions. The current study was conducted to clarify which aspects of social relationships impact the maintenance of function in the elderly, which is defi ned as mortality. The baseline data used in this study was collected in 2008. The participants were elders aged over 65 years, who lived in a suburb community. In total, 536 participants were eligible to be included in the sample, without missing data. The Index of Social Interaction (ISI), which comprises 5 subscales, was used to assess the multiple aspects of social relationships in the elderly. Mortality data from May 2008 till September 2014, which was recorded by the municipality in this area, was used. During the study period, 107 of the participants died and 429 survived. After controlling for age, gender, status of diseases, and lifestyle in 2008, the results showed that the total score of the ISI (HR 1.90; CI 1.12–3.22) was related to mortality, as were the subscales on independence (HR 1.80; CI 1.09–2.97), social curiosity (HR 1.74; CI 1.02–2.96), and participation (HR 2.00; CI 1.18–3.39). The magnitude of signifi cance was the highest for the score on the participation subscale, followed by the total score. The current study suggests that good social relationships are effective in ensuring the maintenance of function in the elderly. In addition, participation and multifaceted social relationships have the strongest impact on mortality in diverse social relationships.

271 23-7

Activity limitation, social and health conditions among Japanese elderly people with hearing loss

Yoko Kobayashi1,2, Nanako Tamiya2, Yoko Moriyama2,3, Haruko Noguchi2,4, Hideto Takahashi2,5, Yui Yamaoka2, Felipe Sandoval2,4, Kazunori Takeda6

1Reasearch and Support Center on Higher Education for the Hearing and Visually Impaired, Tsukuba University of Technology 2Department of Health Services Research, Faculty of Medicine, University of Tsukuba 3Department of Health and Welfare Services, National Institute of Public Health 4Graduate School of Political Science – Public Management Major, Waseda University 5Faculty of Medicine, Fukushima Medical University 6Faculty of Human Science, University of Tsukuba

Objective : We aim to examine the situation of elderly people with hearing loss and the relation with activity limitation, several social and health conditions using nationally representative data in Japan. Methods : Data from a nationally representative cross-sectional household survey of 131,807 aged 65 and over were obtained (prevalence of hearing loss: 11.7%). Dependent variables were socioeconomic status (marital status), subjective symptom (the top ten responses chosen, such as forgetfulness, shoulder stiffness, lower back pain), activity status (activities of daily living: “rising, dressing/undressing, eating, bathing”, “going out”, “work, housework or schoolwork”, “physical exercise (included sport)”, and “other”), and health status (visit hospital, self-reported health, psychological distress). We examined the association of hearing loss for each measure using generalized estimating equations to account for correlated individuals within households. Results : The prevalence of elderly people with hearing loss increased by age groups: 5.9 % for age 65 to 69, 10.8 % for age 70 to 79, 19.6 % for age 80 to 89, 29.3 % for age 90 and older. After controlling for age and gender, our logistic regression shows that elderly people with hearing loss were more likely to be unmarried. Elderly people with hearing loss were more likely to be affecting subjective symptoms include forgetfulness, shoulder stiffness, lower back pain. Activity status was also signifi cant at all activities of daily living settings. We also found that health status among elderly people with hearing loss with positively associated with visit hospital, self-reported health, and psychological distress. Discussion : These fi ndings suggest that elderly people with hearing loss is related to activity limitation, social and health issues in daily life. Further attention should be paid to detailed situation of elderly people with hearing loss with activity limitation and health conditions.

272 23-8

Impact of respite care on speed until admission to 3 types of facility of the elderly certifi ed as eligible for long-term care insurance in Japan: From Survey of Long-term Care Benefi t Expenditures

Yoko Moriyama1,2, Nanako Tamiya2, Akira Kawamura2, Haruko Noguchi3, Hideto Takahashi2,4

1Department of Health and Welfare Services, National Institute of Public Health 2Department of Health Services Research, Faculty of Medicine, University of Tsukuba 3 Graduate School of Political Science – Public Management Major, Waseda University 4 Information management and Statistics, Fukushima Medical University

Objective: We aim to clarify the impact of respite care on the length to admission to either of 3 types of facility (a nursing home, health services facility, sanatorium type medical care facility) of the elderly by care level when certifi ed fi rst as eligible for long-term care insurance (LTCI). Methods: We used the data of all users of LTCI services in Ibaraki between Apr., 2006 and Mar., 2012 from Survey of Long-term Care Benefi t Expenditures. We obtained 3,391 subjects who satisfi ed 1 ~ 5 , simultaneously: 1 aged 65 and over, 2 certifi ed fi rst for on and after Apr., 2006, 3 not institutionalized when certifi ed, 4 care level when certifi ed were 1-5, and 5 moved to facility until Mar. 2012. Endpoint was the admission to facility, and the median of number of month (NM) from the fi rst certifi cation for LTCI to the admission to facility, which was estimated using Kaplan-Meier method for each care level. Adjusted hazard ratio (HR) of admission for the use or not use of respite care were calculated using the Cox proportional hazard model on Care level 1 because it was signifi cant only with foregoing analysis. We adjusted by the age when certifi ed, sex, the use or no use of each home service. Results: The median and 95% confi dence interval (CI) of NM were, Care level 1: 35months (m) (32-38) for respite care users (user), and 27m (23-31) for non-users (non) (p-value<0.01). Care Level 2: user; 28m (24-32), non; 24m (19-29), Care level 3: user; 21m (19-23), non; 19m (16-22), Care level 4: user; 16m (13-19), non; 17m (14- 20), Care level 5: user; 12m (7-17), non; 22m(18-26), not signifi cant with Care level 2-5. Respite care user admit later than non-users with Care level 1 (HR; 0.83, 95%CI; 0.71-0.97). Discussion: Respite care user admit later than non-users if care level certifi ed fi rst were milder. These fi ndings suggest appropriate use of respite care may delay moving to facilities if care level when certifi ed fi rst is milder.

273 23-9

A descriptive study of the length of stay at home in days for long-term-care insurance users with severe disability in a prefecture of Japan

Hiroaki Ueshima1, Nanako Tamiya1, Nobuyuki Izumida2, Akira Kawamura1, Yoko Moriyama1,3, Felipe Alfonso Sandoval Garrido1,4

1Department of Health Services Research, Faculty of Medicine, University of Tsukuba 2Department of Health Services Research, Graduate School of Comprehensive Human Sciences, University of Tsukuba 3Department of Health and Welfare Services, National Institute of Public Health 4Faculty of Political Science and Economics, Waseda University

Background Caring for the elderly with severe disabilities at home is an important aspect of the long- term care in Japan. However, little research has been undertaken to examine how long they stayed at their home. Objective The purpose of this study is to describe the length-of-stay at home (LoSaH) in days for people with severe disability using long-term care (LTC) services stratifi ed by gender, age, and municipalities. Design Cross-sectional descriptive study. Methods We analyzed LTCI claims data from Ibaraki prefecture with permission of the Ministry of Health, Labour and Welfare of Japan. The subjects are persons certifi ed as care level 5 users since March 1, 2006 until February 28, 2012. We calculated LoSaH by summing up the days when subjects were not admitted to care facilities. Then we stratifi ed them by gender, age group, and municipalities. Results The sample consisted of 38032 individuals; 12635 male and 25397 female ones. The mean and standard deviation of LoSaH was 206.7±355.7 days, with a range of 0~2357 days. For male users: 209.7±350.3; days for female ones: 205.3±358.3 days. By municipal body, the highest mean LoSaH was 273.9 days and the lowest at 149.8 days. By age stratifi cation, males in their 90s had the shortest LoSaH; the shortest LoSaH for female users took place in their 80s. Conclusions The LoSaH varied by gender, age groups, and municipalities. Therefore, it is necessary to consider policy or support based on these variations. Future studies are needed to see which factors caused these variations.

274 23-10

Five-year transition patterns of care-need level

Masamitsu Mikoshiba1, Hideto Takahashi2, Tomoko Ito3, Nanako Tamiya3

1Department of Health Services Research, Graduate School of Comprehensive Human sciences, University of Tsukuba 2 Information management and Statistics, Fukushima Medical University 3Department of Health Services Research, Faculty of Medicine, University of Tsukuba

Objective : Care-need level is essential for long-term care insurance (LTCI) because LTCI service is decided dependently on the level and it almost indicates physical functions of the elderly. The change of care-need level is useful for care managers to make new care plans to prevent the elderly from losing their physical functions. But it is not clear enough how care- need levels change. The objective of this study is to show the transition patterns of care-need level. Methods : LTCI service Data from April 2000 to June 2007 were offered from a municipality under the contract of confi dentiality, etc. In this study, we selected the subjects who were over 65 years-old and used LTCI services every month. We observed their care― need level from their fi rst use of the care service to the last use of the fi ve year later in the successive fi ve years of the period. (288 samples : men 71, women 217). And we counted the proportion of increasing (worsening), decreasing (improving) of care-need levels, respectively. Result : The patterns of simple worsening (The care-need level in the last observation was increased than that in the fi rst observation in the throughout 5 years) and monotonically worsening (all the changes of any successive two observational points were non-improving in the period) were was 38.0% (men) and 54.8 % (women), and 29.6%(men), and 30.9%(women), respectively. On the other hand, the patterns of simple improving and monotonically improving were was 26.8% (men) and 16.6 % (women), and 16.9% (men), and 9.2% (women), respectively. Conclusion: There were various transition patterns of care-need levels. They were not always steadily worse, and not few people sustain or improve their care-need levels.

275 23-11

The trial of the shift from tubal to oral feeding in long-term care facilities: a descriptive analysis of the difference among Care-Levels, facility types and prefectures in Japan

Akira Kawamura, Nanako Tamiya

Department of Health Services Research, Faculty of Medicine, University of Tsukuba

Background & Objective: There had been many cases of tubal feeding for elderly people including gastrostomies in Japan. However, we know little about how many people tried to recover taking nutrition from tubal to oral feeding. The aim of this study was to describe the cases of trials of the shift from tubal to oral feedings, especially focusing on the difference among Care-Levels, facility types and prefectures. Method: We employed a descriptive analysis with tables and graphs. Survey of Long-term Care Benefi t Expenditures, the nation-wide claim-based data in the long-term care insurance (the LTCI) in Japan, was used to describe. The observed periods of the data were from May 2006 to April 2013. After removing the observations which were mistakenly input, the sample size of our fi nal dataset was 24,946. Result: Most of the users were nursing care level 5 (N=18,171(72.8%)), therefore the tendency of level 5 was almost the same as that of the whole, while the number of the level 4 to the level 1 users were 5,275(21.1%), 1,225(4.9%), 164(0.7%), 71(0.3%), respectively. The numbers of each LTC facility were 3,902(15.6%) in special nursing homes (SN), 10,249(41.1%) in geriatric health care facilities (GH), and 10,795 (43.3%) in geriatric medical care facilities (GM), respectively. Observing the annual differences of the number of users among prefectures, the largest ones were Tokyo, Aichi, Fukuoka and other prefectures which includes ordinance-designated cities. On the other hand, smallest ones were Shimane, Nagasaki, and some other prefectures. In terms of the annual trend by prefecture, those were generally unchanged or slightly decreased except for 2006-2007 periods. Focusing on the trend in each type of facilities, the tendencies were as follows: the trends in SNs and GHs were similar with total trend. In GHs’ case, that was roughly unchanged during the observed periods except 2006-2007.

276 23-12

How do we share confi dentiality sensitive information in large study group?

Hideto Takahashi1, Enbo Ma2, Nanako Tamiya3

1Information management and Statistics, Fukushima Medical University 2Department of Epidemiology, Faculty of Medicine, University of Tsukuba 3Department of Health Services Research, Faculty of Medicine, University of Tsukuba

Introduction: As well-known, study has “scientifi c” and “ethical” aspects. In this ten years, the surrounding of study has dramatically changed. First, before we start a study, it is now our common sense that study must be approval by Institutional Review Board (IRB) along various guidelines, namely, ethical guidelines for epidemiological research, or ethical guidelines for Human Genome/Gene Analysis research, and so on,. Second, protection of personal information has become high priority in study. Third, we can treat giga-size data (BIG DATA) brought by the development of information communication technology (ICT). Fourth, there are more competitive funds with big money, and it triggers our study group size bigger. Fifth, the government has gradually provided national data to researchers after Statistical Act in Japan was revised. These changes brought us to access national individual- based information, to use them with high security, and to share important information (study plans, the results, discussion for blushing up, documents for publication) in study group. The objective of this presentation is to demonstrate what became problem caused by these changes, and introduce our solutions. Problem: How do we share confi dentiality sensitive information in large study group? Solutions: (1) We construct database system to handle analytic data easily. (2) We separate personal computers (PCs) to analyze data independently (exclusive use for analyzing) of other PCs with treating general information. (3) These PCs are also independent of internet. (4) Confi dentiality sensitive information were shared by CD(DVD). They are sent by special door-to-door delivery service. (5) The second level of these information (results and discussion, etc) are shared through shared Server. We do not use e-mail even they were encrypted. (6) More than everything, it is important to share consciousness of the information security in the group. Conclusion: Now the study environment is changing to the direction that sharing confi dentiality sensitive information in large study group. We must take care the confi dentiality of data, technically and consciously.

277 23-13

Abdominal pain in oldest-old emergency patients

Masatoshi Uchida

Department of Health Service Research, Faculty of Medicine, University of Tsukuba

Background It is diffi cult to make a diagnosis of an elderly with abdominal pain because she or he may have mild complain regardless of having a severe disease. Objective Our aim was to describe characteristics in oldest-old (80 years and older) patients with abdominal pain and to evaluate the relationship between intensity of their pain and hospitalization. Methods We conducted a retrospective observational study of adult patients (18 years and older) who complained non-traumatic abdominal pain and visited an ambulatory emergency department of a community hospital in Japan. The study duration was from January, 2014 to December, 2014. Age, gender, intensity of their pain, patient’s acuity, vital signs, associated symptoms, diagnosis at emergency department, need of Computed Tomography (CT) and emergency department length of stay was collected. Symptom severity is measured on NRS (Numerical rating scale). We compared these characteristics of oldest olds with those of others predict their hospitalization. Results During this study period, 1,783 patients met inclusion criteria. Overall, mean age was 46.2±19.8 years old, Oldest-old patient was 134/1783 (7.5%). Male was 856/1783 (48.0%), and mean NRS was 7.2±1.8, CT were performed 287/1783 (16.1%). Finally, 232/1783(13.0%) patients were hospitalized. Oldest olds were more likely to be hospitalized (53/134 (39.6%) vs. 179/1649 (10.9%), P<0.001) than the others. They also complained more severe symptom (7.8±1.3 vs. 7.1±2.2, P<0.001) than the others. CT was more obtained for oldest olds than for the others (40/134 (29.9%) vs. 247/1649 (15.0%), P<0.001). Others (adults and olds) who were hospitalized appealed more sensitive of pain than non-hospitalized patients (NRS: 7.5±2.0 vs. 7.1±2.1, P=0.008) although oldest-old did not (NRS: 7.8±2.1 vs. 7.8±2.3, P=0.993). Conclusion Oldest-old patients with abdominal pain were more admit hospital than others. However, it was diffi cult to distinguish the necessity of hospitalization only by intensity of their subjective pain symptom.

278 23-14

MafB impairs tumor growth through decrease of tumor- associated macrophages

Yuki Imamura, Michito hamada, Tran Thi Nhu Mai, Megumi Nakamura, Risa Fujii, Yuki Tsunakawa, Takashi Kudo, and Satoru Takahashi

Anatomy and embryology, University of Tsukuba

Tumor contains not only tumor cells but also several immune cells, which are studied as a target for cancer treatment. However such methods have low effi ciency in dropping tumor size. As an alternative, Tumor associated macrophages (TAMs) are getting attention, which induces tumor cell proliferation and inhibits immune responses of T cells. The survival rate of patients with less TAM has risen signifi cantly, suggesting its impactful potential as a new target for cancer treatment. However, the molecular regulation of TAM is still unclear. To study this, we investigated the role the transcription factor MafB. MafB is involved in the differentiation of macrophages and their progenitors (Moriguchi. et al., 2006). Here we show that MafB impairs tumor growth through decrease of TAMs. To examine the Maf B function in TAM, we utilized WT and Mafb-GFP knock-in (Mafb-/-) mice, followed by Lewis Lung Carcinoma (LLC) cells transplantation by subcutaneous injection, resulting in larger tumor in Mafb-/- mice compared to WT. Next, we dissociated these tumors by collagenase A, labeled them by anti-CD11b antibody, a macrophage marker, and calculated macrophages percentage by fl owcytometry. We found that number of TAM was signifi cantly increased in Mafb-/- mice. These results indicate that MafB impairs tumor growth through suppressing TAM proliferation. To explain the role of MafB in TAM proliferation decrease, we tested 2 hypotheses. Firstly, as the progenitor number refl ects the macrophages amount, “MafB inhibits Macrophage progenitor proliferation.” Secondly, since cancer cell factors activate TAMs, “MafB increases the sensitivity against cancer cell factors to facilitate TAM development.” As a result, MafB limited macrophage progenitor numbers in spleen, suppressed TAM, and increased tumor size. Although MafB affects Macrophage progenitors directly, its importance in the sensitivity for cancer factors (hypothesis 2) remains unknown. In conclusion, our fi ndings highlight MafB controlling tumor size by interfering with TAM from progenitor level, which may open doors to new cancer treatments.

279 23-15

Psychosocial and Criminological Factors Related to Recidivism among Japanese Criminals at Offender Rehabilitation Facilities

Kaori Kishi1, Fumi Takeda2, Junko Suzuki1, Takafumi Monma1, and Tohru Asanuma1

1the Doctoral Program in Human-Care Science, Graduate School of Comprehensive Human Sciences, University of Tsukuba 2Faculty of Health and Sport Sciences, University of Tsukuba

Recent crime trends in Japan demonstrate two contradictory natures. While Japan has been known as one of the safest nations in the industrialized world, maintaining a low crime rate, persistent offenders have been casting a shadow over this positive international image. Compared with other age groups, the elderly offenders’ reimprisonment rate has been consistently rising for two decades and strikingly, has risen approximately fi ve-fold since 1994. To develop a better understanding of the factors that affect post-release success and failure, this study investigates the relationships between psychological, socioeconomic, and criminological factors and recidivism among male Japanese criminals at offender rehabilitation facilities. Participants included 96 offenders in rehabilitation facilities who completed the Japanese Criminal Thinking Inventory (JCTI), the Buss-Perry Aggression Questionnaire (BAQ), the Sense of Coherence (SOC) Scale, and socioeconomic and criminological questionnaires. Univariate and multiple logistic regression analyses were conducted. The results indicated that, having committed theft or drug-related crimes and manageability (a subcategory the SOC), were signifi cantly and independently related to the reoffending tendency. Theft and stimulant use were the strongest predictors of recidivism when compared with felonious/ violent/intellectual crimes. Regarding the thefts’ modus operandi, while juveniles and young offenders tend to attempt burglaries, elderly offenders tend to shoplift (Japanese Ministry of Justice, 2014). Repeat shoplifting offenders were likely to be poor, needy, and relatively old (Japanese Ministry of Justice, 2009). Furthermore, the repeat shoplifting rate has increased nearly four-fold since 1994, and male elderly thieves are more likely to be reincarcerated. Hence, this type of offenders’ age has been rapidly increasing in Japan, and this profi le conforms to the samples in this study. Providing practical interventions as per offender type and manageability level will mitigate recidivism risk and help offenders reenter society.

280 23-16

The Effects of Sense of Coherence on Mental Health among Community-Dwelling Older Adults

Takafumi Monma1,2, Fumi Takeda3, Kenji Tsunoda4, Naruki Kitano3, Kaori Kishi1, Sakiko Ozawa1 and Tomohiro Okura3

1Graduate School of Comprehensive Human Sciences, University of Tsukuba 2The Japan Society for the Promotion of Science 3Faculty of Health and Sport Sciences, University of Tsukuba 4Physical Fitness Research Institute, Meiji Yasuda Life Foundation of Health and Welfare

[Aim] Sense of coherence (SOC), a central concept in salutogenesis, has received attention as a way of coping with stress and health promoting ability. While the correlation between SOC and mental health in older adults has been reported in a lot of cross-sectional studies, there is only one longitudinal study on the subject, and it only addresses oldest old (aged 85 and above). Hence, a longitudinal correlation between SOC and mental health in older adults aged 65 and above has not been investigated. Thus, this study examined the effect of SOC on mental health among community-dwelling older adults using longitudinal data. [Methods] In 2011, an initial survey was conducted with 360 older adults aged 65–85 living in Kasama, Ibaraki Prefecture, Japan. In 2012, a follow-up survey was conducted. Of the 157 individuals who fi lled out both surveys (response rate: 43.6%), an analysis was performed on the surveys of 136 individuals (valid response rate: 37.8%) that completed questionnaires. The initial survey asked about demographics (sex, age, years of education, living arrangement, and clinical histories), mental health (K6 Scale), SOC (13-item 5-point SOC Scale), and social network (family, friends). The follow-up survey inquired into mental health and SOC. A multiple linear regression analysis was performed using the initial survey SOC and the change in SOC during both surveys as independent variables, and mental health in the follow-up survey as the dependent variable. Covariates included initial survey demographics, social network, and mental health. [Results] The change in SOC was signifi cantly negatively correlated with mental health in the follow-up survey (β= −0.173, p < 0.05). Furthermore, the initial survey SOC had marginally signifi cant negative correlation with mental health (β= −0.146, p < 0.10). [Conclusion] This study suggests the possibility that SOC are effective for maintaining or enhancing mental health among community-dwelling older adults.

281 23-17

Age differences in psychosocial factors of work engagement among company employees

Sakiko Ozawa1, Fumi Takeda2, Takafumi Monma1,3, Mieko Abe1 and Noriko Furutani4

1The Doctoral Program in Human-Care Science, Graduate School of Comprehensive Human Sciences, University of Tsukuba 2Faculty of Health and Sport Sciences, University of Tsukuba 3The Japan Society for the Promotion of Science 4cuorec3, Inc.

[Objectives] In recent years, several efforts have been made to encourage mental health and work engagement among company employees. In our aging society, it is important to promote work engagement, particularly among the elderly. However, no previous study has focused on age differences in psychosocial factors of work engagement. This study addresses that gap in research. [Methods] In April 2015, a web-based questionnaire was administered to 307 employees of a com- pany. The items covered demographics (sex, age, years at the company), work engagement, job demands (quantitative and qualitative burden, physical demands, and job control), job re- sources (social support of supervisors and coworkers), organizational environment and tradi- tional culture, and personal resources (the Sense of Coherence (SOC): meaningfulness, com- prehensibility, and manageability). A multiple regression analysis was performed to clarify the relationships between work engagement and the explanatory variables, and then Spearman correlation coeffi cients were calculated in each age-stratifi ed group. [Results] Work engagement was signifi cantly associated with quantitative burden (β =−0.209), qual- itative burden (β = 0.366), organizational environment (β = 0.274), sex (β = – 0.172), and age (β = 0.178) (p < 0.05). In the case of age-stratifi ed, there were age differences of psychosocial factors of work engagement. In the group above age 50, work engagement was negatively correlated with traditional culture (r=−0.318) and positively correlated with having a good organizational en- vironment (r=0.392), support from supervisors (r=0.314), manageability (r = 0.277) and mean- ingfulness (r = 0.297) that are components of SOC (p < 0.05). [Conclusions] This study indicates that age differences exist in psychosocial factors of work engage- ment among company employees. It is important to examine measures of worksite mental health promotion with considering elderly employees’ characteristics.

282 23-18

Perceptions of Aging and Disability among College Students in Japan

Nick Warren1,3, Akiko Kamimura2, Ha Ngoc Trinh2,4, Ana Kanaoka3, Ai Ishikawa3 and Katsuo Yamanaka3

1Department of Psychology, University of Utah 2Department of Sociology, University of Utah 3Department of Disability Sciences, University of Tsukuba 4Department of Sociology, Vietnamese National University

By launching the Long-term Care Insurance program in 2000, and ratifying the United Nations` Convention on the Rights of Persons with Disabilities in 2014, Japan has been taking signifi cant steps to support their elderly population and individuals with disabilities. However, information is lacking on the understanding and opinions of either of these groups among Japanese college students, many of whom will have signifi cant impact on the development of relevant programs in years ahead. The purpose of this study is to explore the thoughts, ideas, and experiences of a sample of Japanese college students on 1) the elderly, 2) individuals with a physical disability, and 3) individuals with a mental disability. We held two focus groups with a total of 13 students studying fi elds directly relevant to the three topics (recruitment for groups consisting of those studying less relevant fi elds is underway) in the summer of 2015. We are planning to hold two more focus groups. We fi rst asked the students to fi ll out a demographic questionnaire. We then asked questions, facilitating discussions on the participants` personal impressions on each of the three groups in Japan, barriers they believe each to have, and solutions they believe exist. Preliminary results refl ect impressions of Japanese elderly as especially energetic and long-living, but having barriers of physical impairment in daily living and inability of many to obtain care if physical functioning is declined. Provision of money to the elderly and the hiring of more foreign care workers were tentatively discussed as solutions. Individuals with physical or mental disabilities were seen as lacking suffi cient accommodations and being misunderstood by the general public. College students are aware of the issues of aging and a variety of disabilities but need more direct exposure to individuals with disabilities.

283 23-19

A Comparative Study of Community-based welfare system in Japan and China

Keishi Ebisawa

Graduate School of Comprehensive Human Sciences, University of Tsukuba (Register Student)

Since the 80’s century, the major phenomenon of the fertility with aging population has rapidly grown in Japanese society. In one aspect, the proportion of elders in the total population are continual to increase, and same as to the level of social economical burden including fi nancial expenditure, family caregiver’s care burden and so on. In face of increasingly social economical burden, the Japanese government began to reform the social welfare system in the late 1980s, implemented the Long-Term Care (LTC) system in 2000. The signifi cance of the modifi cation is legalization of a community-based welfare system. Community Welfare in Japan's social welfare system becomes one of the main purpose. The mainstream of the social welfare system has changed from an institutional welfare system to a community-based welfare system. China has been entering the ageing society since 2000. Population aging becomes the critical issue in social development nationwide. It had been noted that the burden of provision, medical care, and social services for the aged is more seriously. Due to the higher and faster degree of aging population, the traditional mode of family endowment has failed to meet the requirement of economic and social development. In order to further satisfy the home endowment service demand of the elderly, the Chinese government has also enacted a series of measures, tried to constitute a community-based welfare system and amend the relevant law and policy. Under this background, this study has compared and discussed the administrative system, community welfare service providers, contents of community welfare services, the role of providers and community in Japan and China.

284 23-20

Population aging and social issues in West Africa: A comparative analysis of Benin and Japan

Bakumyna Sekpon

Social Systems and Management, Graduate School of Systems and Information Engineering, University of Tsukuba

Japan has the oldest population among countries in Eastern Asia. Due to a decline in fertility after the Second World War, the decrease of the young population was more rapid than it had been in any of the industrialized countries of the time. Based on some estimation Japan is expected to become the oldest population in the world. On the other side, in Sub- Saharan Africa the number of people aged 60 and over will nearly double from over 35 million in 2006 to over 69 million in 2030. Benin, a West African country is also undergoing population aging. This study examined the infl uence of population aging on social issues both in Benin and Japan. The aim is to determine if population aging has a negative impact on the development of the country or if in contrary it can be used as a positive tool. In the fi rst part we will describe the status and change of the population both in Benin and Japan. The second part is a comparative analysis of the impact of population aging on social issues both in Benin and Japan. In the third part we will demonstrate how ageing phenomenon is observe by Benin people and it implication in the society development. Through a quantitative approach combine to a qualitative approach, we will describe how each society can learn from the other in order to improve their social policies.

285 23-21

Literature Review on the Relationship between Social Network and Quality of life of Older People in African Countries

Josephine Laker1, Felipe Sandoval2, Nanako Tamiya3

1Department of Health Services Research, Graduate School of Comprehensive Human Sciences, University of Tsukuba 2Faculty of Political Science and Economics, Waseda University 3Department of Health Service Research, Faculty of Medicine, University of Tsukuba

Background: There has been substantial documentation on the association between social network (SN) and quality of life (QoL) in developed countries. However, little is known about it among older people in Africa. Objective: To grasp the present situation of the association between SN and QoL of older people in African countries. Search Strategy: We searched PubMed as of July 5th, using as keywords: “social network or social capital or social support” and “quality of life or wellbeing” and “Africa or African”. The total search results were 163. Following our exclusion criteria, 10 studies that did not mention the study population in their abstracts; 142 studies with different study populations; 5 studies that were not carried out in Africa, and 2 studies that compared SN with variables other than QoL were excluded. Results: Regarding measurement, four studies analyzed the relation between SN and QoL, defi ning SN as either group-based or personal SNs, and as access to network resources. In one study, QoL was measured using WHOQOL-BREF, a short version of the WHO QoL scale, whereas another study used CASP-12 (v2). Two studies did not specify their measurement for QoL. Regarding the direction of the effect, three studies reported that SN is benefi cial to QoL and one study reported that personal networks and access to network resources are benefi cial to mental but not physical health.

286 23-22

Comparison of population trends of new immigrants in Japan and Finland: a literature review

Reiko Hoda

Department of Social Work, Kansai University of Welfare Sciences

This study reviews the literature on population trends of new immigrants in Japan in comparison with the immigrant population in Finland. After reform of the Immigration Control and Refugee Recognition Act, large numbers of Japanese Brazilians came to Japan as dekasegi (seasonal) workers. This infl ux of Nikkeijin (descendants of Japanese emigrants) constituted the so-called “dekasegi phenomena.” After the fi nancial crisis in 2008, Nikkeijin who are given access to residential status are more likely to change from long-term resident (teijyu-sha) status with no restrictions on employment to permanent resident (eijyu-sha) status with no limitations on length of stay. On the other hand, Nikkeijin face diffi culties integrating into Japanese society. They are expected to integrate with Japanese culture, customs and language. In Finland, there are special returnee immigrants—the so-called “Ingrian Finns.” Ingrian Finnish returnees are persons from the former Soviet Union who have Finnish ancestry. Also people with a parent or grandparent who is or was a native Finnish citizen are considered returnees of Finnish origin. Finland faced labor shortages in the 1980’s so returnees from Russia and Estonia were encouraged to return to Finland. However, this remigration policy will end in 2016 and after that, Ingrian Finns will no longer be regarded as returnees. Ingrian Finns who have a strong Finnish identity and good Finnish language skills, have integrated well into Finnish culture, whereas others who have a complex view of their identity and poor language skills are unable to fully integrate. Based on this review, both Finland and Japan have looked to immigration as a potential solution to resolve the problem of an aging society. Also, these immigrants (Ingrian Finns and Nikkeijin) are expected to make up for the labor shortage. However, both immigrant populations face diffi culties integrating into the countries they have migrated to.

287 23-23

The Relation between Informal Care Provision and Major Depressive Disorder among Rural Elderly People in South Africa

Felipe Sandoval1,2, Tamiya Nanako3, Haruko Noguchi1

1Faculty of Political Science and Economics, Waseda University, Japan 2Department of Health Services Research, University of Tsukuba, Japan 3Faculty of Medicine, University of Tsukuba, Japan

Aim: Aging population in South Africa is increasing, but not the evidence of the challeng- es. Late-life depression among old caregivers is one of them. The literature reports the adverse effects of caring for adults. However, the effects of caring for children remain inconclusive. We aim to explore the relation of provision of care and major depressive disorders (MDD) in rural older persons in South Africa. Method: We carried out a cross-sectional, study using the SAGE Well-being of Older Peo- ple Study (WOPS) on South Africa by WHO (2010). The sample included 219 HIV-negative subjects aged 50+, who had an adult child HIV-infected or a dead adult household member in the prior 2 years. MDD was measured using the DSM-IV criteria, and provision of care ac- cording to the answer to “Are you providing any physical or nursing care to any adults/children resident in your household?”. Results: The prevalence of MDD was 38.4%. Care was provided by 66.2% of the subjects. Caregivers of either children or adults were 21.50% (18.70% to only children and 2.70% to only adults). Bivariate analyses show that, compared to non-caregivers, caregivers of only children have a likelihood more than double of depression (2.43), while caregivers of adults have over 20 times (23.46), and caring for both over fi ve times (5.30). Other factors associated to MDD were female sex; no education; worse fi nancial condition since 3 years ago, symptoms of heart disease, arthritis, cataracts, hypertension, and higher disability scores. In the multivariable model, caring for either children or adult has an Odds Ratio (OR) of 7.8, while caring for both, child and adults, has an OR of 13.4, compared to non-caregivers.Conclusions: In South Africa, we found that providing care for either children or adults has an adverse effect, however, caring for adults has a stronger detrimental effect. Our fi nding stresses the need for supporting older caregivers in order to prevent depression.

288 24 Borderless Challenges of Global Aging: Role of Young Power 2015

Wednesday, September 30 Venue: Conference Room 303

Borderless Challenges of Global Aging: Role of Young Power 2015

The Medical Sciences and the Humanities & Social Sciences have held joint seminars called “Borderless Challenges of Global Aging: Role of Young Power” since 2012. In this seminar, students learn about the situation and social issues in aging and aged countries, and discuss the role and power of young people for challenging these issues using interdisciplinary and comparative research methods. This year the focus is on “end-of-life”. Our students will present their work at the TGSW 2015.

Session Organizers: Nanako Tamiya, Miyoko Motozawa, and Shiho Kashiwagi

Part One Chair: Shiho Kashiwagi, Faculty of Medicine Xueying Jin Doctoral Program in Human Care Science 9:35-9:43 Elderly care in China Sun Jiayi School of Life and Environmental Sciences 9:43-9:51 Population aging in China and development of elderly-health-care system Keishi Ebisawa Comprehensive Human Sciences (credited auditors) 9:51-9:59 An additional reward system for end-of-life care services in Japan Ho Pui Man Iris School of Social and International Studies 9:59-10:07 Singapore and the issue of senior citizens Ellen Chen School of Social and International Studies 10:07-10:15 Policy of elderly and long-term care in Taiwan Orakanjana Ariyapinyopas School of Social and International Studies 10:15-10:23 On aging population in Thailand Luong Anh Nguyet School of Social and International Studies 10:23-10:31 Young generation as vital key to sustain the elderly: a case study in Vietnam Utami Nadia Putri College of Agro-biological Resource Sciences 10:31-10:39 Borderless Challenge of Global Aging and the Role of Young Power in Indonesia Chiaki R. Suzuki School of Social and International Studies 10:39-10:47 Filipino healthcare workers in demand for the aging society of Japan Hikari Hata School of Health and Physical Education 10:47-10:55 Poverty of aged women in India -Support for widows- Singh Rupa School of Social and International Studies 10:55-11:03 Population aging in Nepal Part Two Chair: Felipe Alfonso Sandoval Garrido, Waseda Univeristy and CGAT Kaiki Fujita College of International Studies 11:03-11:11 Health services in Dubai, UAE and analysis of its long-term care Nweke Ikenna Steve School of Social and Ineternational Studies 11:11-11:19 Aging population in Nigeria : Key issues and recommendations Ugboma Maureen Ndali School of Social and International Studies 11:19-11:27 Aging in Nigeria

289 Carolyn Kemunto Master of Public Health Program 11:27-11:35 The emerging ageing population and their state of life: a case study of Kenya Chrispin Manda Master of public Health Program 11:35-11:43 Elderly persons are neglected and face many challenges in Malawi Part Three Chair: Felipe Alfonso Sandoval Garrido, Waseda Univeristy and CGAT Cristina Mihaela Asavoaie School of Social and International Studies 11:43-11:51 Global aging and role of young power in Romania Taylor Quanan School of Social and Ineternational Studies 11:51-11:59 Aging in Russia Natstumi Shimafuji School of Nursing 11:59-12:07 Principles and organisation of the social security system for family care in Sweden

290 24-1

Elderly care in China

Xueying Jin

Department of Health Service Research, Doctoral Program in Human Care Science

The population of China is 1.4 billion and represents one-fi fth of the world population. The land area of China is 9.6 million km2 and it is geographically huge and varied. It is the world’s fastest-growing major economy, with growth rates averaging 10% over the past 30 years. On a per capita income basis, China ranked 77th by nominal GDP and 89th by GDP (PPP) in 2014, according to the International Monetary Fund (IMF). About religion, although Chinese have the freedom of choosing religion from 1993, the Government implemented an atheist education system from a young age.By the end of 2012, people over 60 represented more than 200 million, about 14.9% of the population. Growth of China’s elderly population is happening at a time of rapid increase in urbanization and industrialization, all of which have weakened traditional family support networks. Furthermore, the tradition of living with their parents are breaking down due to changing lifestyles - and the consequences of the one- child policy. A nationwide survey found that about 23%of China’s seniors over the age of 65 live by themselves. In the present, the elderly has to deal with their late years, when their families cannot take care of them. Therefore, the need for elderly health care has drastically increased due to the increasing trend in aging population as well as the changing in the lifestyle. According to Survey on Demands on Medical Service, the proportion of elderly self-reported chronic diseases is 79.91%, and only 20.25% self-reported to be healthy. Disabled people tend to choose home care, accounting for 35.57% of the demand. The second choice is nursing home, whose percentage is about 29.84%. Home care is provided by basically three caregivers: spouse, children and house maids.

291 24-2

Population aging in China and development of elderly-health- care system

Sun Jiayi

School of Life and Environmental Sciences, College of Agro-Biological Resource Sciences, University of Tsukuba

Nowadays, Chinese elder people face many social issues including pension and medical care coverage for rural elderly, lack of long-term care services for both urban (53%) and rural (66%) elderly and so on. This is led by a large population, unbalanced gender groups and low birth rates (1.20% in 2014). Additionally, high urbanization also increases the gap on education, economy and so on, between urban and rural areas.In China, because of the low birth rate and economic situation, the younger generation has a heavy responsibility, but limited time and efforts to take care for the elderly. Moreover, older people do not have enough welfare and care from younger generations. In some rural regions, younger adults go to larger cities for work, which leads to neglecting older persons’ situation and needs.The state, as the major policy supporter, struggles to provide comprehensive services due to extensive land areas, rapid increasing of the aging population and a diminished economic situation. The market economy now in China is promoted by three forces, including state-owned enterprises (41.86%), collective companies (33.94%) and private businesses (24.20%), which suggests limited funding for the government in a market fi eld, while increasing taxes would cause other social issues in other fi elds.According to a survey by the government, now there is 15.5% of older people aged 60 and over)in China and estimate that there will be 22.01% by 2050, which would seriously affect the labor force and cause more social issues. In order to develop a health care system for the elderly, both government and public support would play an important role.

292 24-3

An additional reward system for end-of-life care services in Japan

Keishi Ebisawa

Graduate School of Comprehensive Human Sciences, University of Tsukuba (credited auditors)

The aim of this study is the introduction of end-of-life care in Japan, particularly the additional reward system for end-of-life care services. The implementation of an end-of-life care system is essential for providing the elderly with better end-of-life. End-of-life care is closely related to bioethics and it is expected to secure and maintain the maximum dignity of senior citizens. It would become a major premise of the implementation to respect the needs of the older persons. In a White Paper on the aging society, reported by Cabinet offi ce in 2015, 54.6% of those aged 65-year-old and over choose “at home” when answering the question “If you had an incurable disease, where would you like to be at your last moments”. If the question did not have the condition of an “incurable disease”, this percentage could be expected to be higher. In the same survey, 91.1% say that they would not choose to prolong life and hope to die a natural death without life-prolonging treatments. In other words, a large number of the older persons hope to have a natural death at their own house. Under this circumstances, it comes into question how to implement an end-of-life care system. Additional rewards are an incentive system to end-of-life care services. It is one of the characteristics of the Japanese end- of-life care policy. This study will introduce the current system and features of the additional reward system for end-of-life care services in Japan and discuss the evaluation system of the home care services.

293 24-4

Singapore and the Issue of Senior Citizens

Ho Pui Man Iris

School of Social and International Studies, University of Tsukuba

Singapore, one of the most successful fi nancial centers in the world, is now facing the challenge of an ageing society, as other developed nations. The total land area of Singapore is only 718.3m2. However, there is a dense population, of nearly 5.4 million, according to the national report in 2013.Ageing population takes place due to a decreasing birth rate and improvements in medical technology, prolonging the life of the citizens. In Singapore, there was a baby boom after the Second World War and the government started family planning policies by encouraging giving birth to two children per family. During the following ten years after World War II, the population had grown 84.7%, while in the past decade, we grew only 40.9%. The current total fertility rate in Singapore is 1.29. Birth rate decreased remarkably and baby-boomers are now becoming senior citizens. As soon as the senior citizens are not capable of living alone or without care, the society, especially the younger generation will have to contribute to the welfare of previous generations. The struggle between the need to give quality life to the elderly and the decreasing young power is the main problem that governments around the world are trying to solve. In Singapore, there are public long-term care services that help individuals or families to take care of their aged family members when they cannot. Some of these services include: home medical care, home nursing care, home therapy, rehabilitation services, day care services, and more. However, the number of older persons covered by these services is very limited. The government has plans to increase the number of beds in nursing homes, and the places where caregivers are allowed to provide their services. All these services are funded by insurance funds and taxes. Hopefully, the economic growth of the country would allow the provision of funding by the current work force to the elderly care.

294 24-5

Policy of elderly and long-term care in Taiwan

Ellen Chen

School of Social and International Studies, University of Tsukuba

Taiwan’s main principles and organization of the social security system focuses mainly on the middle-low-income elderly who lives alone. Programs, including the 10-year long-term care plan, are implemented as a result to improve the quality of the long term care system for the elderly. These programs focus mainly on providing home nursing services, health care, physical therapy at home and in the community, the purchase and lease of assistive device services, house-remodeling for environmental improvements, meals for the elderly, respite- care services, transportation services, and long-term care facility services. Many elderly rely on migrant care workers for care, resulting in diminished role of the family in elderly care. Taiwan became an aging society, as defi ned by the World Health Organization, in 1993. Currently, elderly aged 65 year-old and over accounts for 10% of the population in Taiwan. As this trend continues, Taiwan will soon face the challenge of the long-term care service network being insuffi cient due to the increasing demand and decreasing fi nancial resources, both government and family ones. The impact of rapid population ageing raises many healthcare questions, including the long-term care of disabled people. To conclude, in order to improve long term care services for the elderly, the role of healthcare professionals and research should be improved. In addition, the government should create policies to increase the number of caregivers in the workforce and provide quality long-term care services.

295 24-6

On Aging Population in Thailand

Orakanjana (Eve) Ariyapinyopas

School of Social and International Studies, University of Tsukuba

Thailand is located in Southeast Asia with a population of nearly 67 million people in 2014. Its GDP reached US$15,319 with an average monthly income of $400. The major religion is Buddhism (93.2%), thus many activities and traditions are connected to this religion. One of these traditions is the Buddhist concept of paying back to your parents their unconditional love when they cared for you. However, many traditional beliefs are shifting, due to changes in demography, socio-economics, and familial structure. In 2010, when the older population reached 7 million (11.5%) in the second most rapidly aging country in Southeast Asia, it proved the need of more comprehensive health-care services and social support for its senior citizens. Along with the aging issue, we observe the decline of the total fertility rate of Thailand, which reached a record low of 1.5 children per woman in 2012. This rate plummeted from the 6 children per woman in earlier decades. National policies were put into force to tackle these challenges. In 1982, the National Elderly Council was created to start working on cooperation and policies on ageing. The aforementioned policies included the National Long-term Plan of Action for the Elderly (1986-2001) and the Second National Plan for Older Person (2002-2021). The former is created earlier to give support for the implementation of government policies on caring for the elderly and was utilized as a guideline for actions by authorized organizations on elderly activities. The latter is focused on developing policies and programs to aid the rising number of older people. Successful programs include the promotion of positive attitudes, health, and social protection. The LTC public services are funded by the government from the tax and insurances of the citizens.

296 24-7

Young generation as vital key to sustain the elderly: a case study in Vietnam

Luong Anh Nguyet

School of Social and International Studies, University of Tsukuba

Vietnam is one of the fastest ageing countries in Asia. By 2050, the proportion of aged people in the total population will triple to reach over 30%, while the birthrate has dropped signifi cantly. As a result, the elderly play an increasingly important role in keeping social and political stability. Vietnamese public policy makers have been facing big diffi culties in providing good universal support for the aged and encourage them to actively participate in local community activities. With such challenges, young generations emerge as a prominent force of care and funding, especially in the context of a long standing culture of close relation between family generations. In this presentation, I would like to discuss how public policies should be fl exibly adjusted according to cultural aspects regarding the future of the aged population. Proposed changes will focus on 2 pillars: 1) the role of young people in a) facilitating a fi nancial scheme for the elderly, b) assisting home primary health care, c) encouraging the elderly to continuously use their experience to contribute to society and 2) how young people could prepare themselves through appropriate knowledge to carry out their historical mission. In the fi nal part, I would like to analyze some lessons that could be learnt from Japan, which could be considered as a role model country in dealing with aging problems, given that Japan and Vietnam share some cultural traits.

297 24-8

Borderless Challenge of Global Aging and the Role of Young Power in Indonesia

Utami Nadia Putri

College of Agro-biological Resource Sciences, Faculty of Life and Environmental Science, University of Tsukuba

The number of elderly in the total world population has been rising as the result of declining fertility and increased longevity. Indonesia is experiencing the same and heading to an ageing population. Indonesia has the fi fth-largest elderly population in the world. There were 21 million older people in 2012, and expected to increase from 11.34 percent in 2020 to 25.5 percent of the total population by 2050. The ageing process is often followed by major health diseases. In the case of Indonesia, the fi ve leading causes of deaths include coronary heart, diabetes mellitus, TBC, hypertension and chronic pulmonary diseases. Other consequences of ageing include social and economic aspects. Economies are globalizing and people are more likely to live in cities. Around 51.5 percent of the total population lives in rural areas where agriculture and fi shery are the main sources of income. Around 90 percent of older people are economically active, but their income is uncertain and their job is lacking in social protection. In order to maintain the quality of life for older people, policy makers need to secure their fi nancial status. Since they grow older, they are not capable enough to work. 50 percent of older persons are not economically active and ending in the income dependency from their previous employment and the support provided by others. Old age dependency ratio is expected to increase from 13.3 percent in 2012 to 17.2 per cent in 2030. Disability increases with age and older people suffer from diffi culties in performing their daily activities. Health care should be prioritized for old women, who live alone and in rural areas. In addition to the social support from the government, it is also important to maintain the traditional culture of care by their children or relatives.

298 24-9

Filipino healthcare workers in demand for the aging society of Japan

Chiaki R. Suzuki

School of Social and International Studies, University of Tsukuba

Japan experiences what many developed economies are facing, an aging society. However, this issue is more alarming in Japan than in any other nation. With low fertility rates and a growing elderly population, Japan is faced with hurdles on its economic future. Today, services for the elderly are strongly needed and more will be in demand in the near future. The government has started to implement policies to cater its rapidly aging population. One of these policies is to encourage the Filipinas already residing in Japan to work in the healthcare industry. Through the Japan-Philippines Economic Partnership Agreement signed in 2006, more job opportunities for Filipinos have opened. To get these jobs, nurses and caregivers are trained and are expected to pass the Japanese nursing licensure examination to continue working in Japan. However, only few pass the exam and the rest end up going back to the Philippines. The questions, which are written in Japanese, are seen as the main reason for the very low passing rate of Filipino nurses. Having considered this, the government decided to allow Filipino and Indonesian trainees to stay for one more year and have another chance to take the licensure exam. The effectiveness of this measure has not been assessed yet. In this paper, the role of Filipinos in the aging society of Japan and the possible outcome of the aforementioned agreement is discussed.

299 24-10

Poverty of aged women in India -Support for widows-

Hikari Hata

School of Health and Physical Education ,University of Tsukuba

This paper aims to analyze the factor related to the poverty status of aged women who live in the countryside of India, especially that of widowed women. About 80% of the aged people live in the countryside and less than 20% of the aged women were economically independent. The wage difference between men and women is 24.81% and ranked as sixth highest in the world. Even if these women were not independent, they could live with the support of their family. However, there are cultural and religious problems in India that hinder this. In the Hindi society, people still believe that widows are undesirable. Widows are given poor meals and cloths, and sometimes abandoned because of this tradition. In one of the most famous Hindi holy places, called “Brindavan”, the state and government provide shelter for them. In other cases, followers of Jainism donate meals and followers of Ashram and Sikhism can get food in the temples. However, the QoL of these widows are not good enough. The number of facilities are not enough and their surroundings are far from suitable. Therefore, the government enacted a law entitled “Maintenance and Welfare of Parents and Senior Citizens Act” in 2007. This legislation make it a legal obligation for children and heirs to provide maintenance to senior citizens and parents, by providing a monthly allowance. This act also provides a simple, speedy and inexpensive mechanism for the protection of life and property of the older persons. Besides this legislation, the government makes the effort of increasing the number of facilities. Nevertheless, their condition is still poor. Thus, it is necessary the cooperation with NGOs and other organizations for improvement.

300 24-11

Population Aging in Nepal

Singh Rupa

School of Social and International Studies, University of Tsukuba

Nepal is in a demographic transition, where the ageing index for Nepal is unlikely to grow rapidly. The current ageing index for elderly aged 65+ years reaches 10.69 % which is expected to increase to only 12.65% by 2031. However, if we see the absolute fi gures, the number of aged 60+ years will increase from 1.6 million in 2006 to 2.79 million by 2031. Additionally, the percent of old among aged persons is increasing rapidly from 10.51% in 1911 to 20% in 2001. To deal this growing number of aged persons will be a diffi cult task for both the Government and society. Although ageing is still not a social or an economic problem in Nepal, problems of medical care are serious [Aging Concern Society of Nepal, 2002] and changes in traditional lifestyles may cause serious problem regarding ageing in decades to come. The elderly population growth rate per year has always been more than the total population growth rate in Nepal, with a decreasing infant and maternal mortality. In addition, the dependency ratio is showing an increasing trend due to youth migration. Therefore, a comprehensive system, including a special geriatrics program and responsive policy environment, is needed to ensure the welfare of senior citizens and meet the needs of an ageing population. Ageing itself is a worldwide and long term global trend, where every country passes through the phases of demographic transition in which the proportion of the elderly people dynamically changes. In Nepal, the size and the ratio of the older population seem to increase over several decades, but not at the rate or size of those in developed countries, like Japan and Germany.

301 24-12

Health services in Dubai, UAE and analysis of its long-term care

Kaiki Fujita

College of International Studies, University of Tsukuba

Dubai is the second largest emirate in the United Arab Emirates (UAE), and its spending on preventive services and inpatient services is the highest-costing component of current health expenditures (CHE). However, Dubai spent only 0.02% of its CHE on long-term care, compared to an average of 11% by Organization for Economic Cooperation and Development (OECD) countries (Hamidi, 2015). Moreover, the availability of health resources is low in Dubai by OECD standards, and in the available indicators, Dubai lies well below the average of OECD countries (Hamidi, 2015). Considering its low expenditure on long-term care, the number of physicians per capita increased substantially in Dubai over the past 2 decades and has reached 27 per 10,000 people. However, it remains well below the average of 32 in OECD countries. Furthermore, there were 56 nurses per 10,000 people in Dubai in 2012, much less than the average of 87 in OECD countries, and the total bed capacity in Dubai was 3,815 beds in 2013, which can be translated into 19 beds per 10,000 people – well below the average of 48 beds in OECD countries the number of physicians per. This current situation would become a serious problem in the future. As birth rate in UAE fell by nearly 50% from 1990 to 2007; from 4.4 children per woman to only 2.3. Additionally, life expectancy in Dubai is high at 77.9 years for females and 72.7 years for males, and these numbers continue to improve. Therefore, needs of long-term care will become higher in Dubai, and in order to cover up the demand of long-term care, its government had better improve its health policy in advance.

302 24-13

Aging population in Nigeria: Key issues and recommendations

Nweke Ikenna Steve

School of Social and International Studies, University of Tsukuba

In 2013, Nigeria, with a population of 174,507,539 according to the CIA World Fact book, is the most populated country in Africa and occupies the ninth position in the world. Life expectancy at birth is 51.6 years for both sexes. The population growth rate from 2000 to 2005 was 2.5%, with only 5% of the total population aged 60 and over. Ageing has become a global phenomenon and certainly a critical policy issue, getting some attention by governments of developing countries, like Nigeria. This attention is refl ected in the government’s economic and social development strategy. Worldwide, an unprecedented number of older people is living in developing and middle income countries, now experiencing rapid demographic shifts. These countries go from high mortality and high fertility to much low fertility and long longevity. Nigeria is not an exception. While population ageing in developed countries evolved gradually allowing the improvement of living standards, for developing nations, population aging is occurring more rapidly because of rapid fertility decline and increasing life expectancy and youth migration. Nigeria, like other African countries, sees this emerging issue as a serious future challenge. The ineffectiveness of the state dealing with issues such as brain-drain, non-payment of pensions, insuffi cient social services, and health facilities are key issues to provide for the needs of a rural agrarian ageing population in Nigeria. Nowadays, Nigeria has the highest older population, along with the largest total population in Africa and the ninth in the world. It is estimated that by the year 2025 the population of Nigerians aged 60 and above will constitute six percent of the entire population. The health care and welfare system to cater for the aged has become a heated topic in the country. What are the problems? How serious are they? Are there ways out?

303 24-14

Aging in Nigeria

Ugboma Maureen Ndali

School of Social and International Studies, University of Tsukuba

The condition of older people in Nigeria is defi ned in two ways. Demographic fi gures provide information about population aging in Nigeria, showing signifi cant aspect of the living conditions of older people. From a psychosocial perspective, living conditions of the elderly take into consideration economic diffi culties, the role of the family and institutional care. As an example, the results of a survey on life-satisfaction of older persons is presented. This piece of work would emphasize the integral role of older persons in the Nigerian society and future problems arising from the development of the population. Nigeria has not yet enacted a National Policy on the care and welfare of the aged. It has been a draft since 2003. In coming years, older population of Nigeria is expected to increase in numbers, along with life expectancy. This paper emphasizes the factors that need to be put in place in other to support the elderly, such as care provision; however, the government and the political leaders think that provision for the elderly is a main responsibility of the families and that policy should address the young, children and women. In addition, the Contributory Pension Scheme does not cover all the elderly and it is designed for those who work or worked in the formal sector. Finally, to eliminate elder abuse and neglect; the government should create awareness on this issue and provide good quality care through public health policies.

304 24-15

The emerging ageing population and their state of life: a case study of Kenya

Carolyn Kemunto1, Yukiko Wagatsuma2

1Master of public Health Program, Department of Clinical Trials and Clinical Epidemiology, University of Tsukuba 2Faculty of Medicine, Department of Clinical Trials and Clinical Epidemiology, University of Tsukuba

Kenya is one of the developing countries whose economic status has improved from low- income country to middle-income one. Thus, most of the middle class is starting to live longer into old age. One of the biggest increases in ageing population in Africa is expected to occur in Kenya, where it is projected that by 2050, there will be a 470% increase in the elderly population. However, discrimination and inequalities still affect the living standards of this emerging group in Kenya. Older people are especially vulnerable to social, political and economic factors, and require prompt interventions to enable them to grow old in dignity. We use literature review and meta-analysis to identify the older populations, their problems, and critical policies and interventions by the government to address the challenges of old age in Kenya. There has been an increase in the elderly population since 1950 when elderly >80 years was 0.3% of total population. Recently approximately over 1.2 million people are over 65 years of age which is 2.8% of the total population in Kenya (45,010,056).The elderly are projected to increase up to 13% by 2050. Females (56.3%) live longer than males (43.6%) with a present life expectancy for females of 65.1 years, exceeding that of males at 62.06 years. Elderly people face problems, such as such minimal savings for their old age,, discrimination by health services and neglect by their families. With the growing rate of the elderly, the government has come up with policies to improve their lives. These include subsidized food and housing, access to health care, free education, social security, such as pension schemes and cash transfers to vulnerable elderly people. This study concludes that Kenyans do not realize that old age is a process that needs both health and fi nancial preparation. Also, government policies have not adequately recognized the impact of old age on the economy and lives of the elderly. Therefore, awareness of younger people to plan for old age and take care of the elderly, prior planning, generation of policies addressing the stability and resource allocation should be prioritized to address the problems faced in old age.

305 24-16

Elderly persons are neglected and face many challenges in Malawi

Chrispin Manda

Master of Public Health Program, Department of Clinical Trial and Clinical Epidemiology, Faculty of Medicine, University of Tsukuba

Global aging is recognized as one of the major challenges of the 21st century. The elderly increased from 8% in 1950 to 12.4% in 2010, and estimated to reach 25.1% of the total population by 2050. This challenges existing health care services, family relationships, social security, and pension programs. Different approaches have been taken in various countries to handle the problem. This study was conducted, through a literature review, to investigate this problem in Malawi and mechanisms putinto place to take care of the elderly. It was found that the proportion of the elderly has remained relatively small from 1950 to 2008 (people aged 65 were 3.1% of the population in 1950; while people aged 60 were 5.12% and 65 were 3.1% in 2008). The illiteracy levels of the elderly are high, particularly for women (87.28% for female 65, and 33.95% for male 65). The proportion of elderly is not threatening which has led decision makers to neglect the provision of care for the elderly. Disability increases with age. In Malawi, a 45-year-old woman is expected to spend 58% of their remaining 28 years with functional limitations, while men of the same age are expected to live 41% of their remaining 25.4 years with functional limitations. Malawi’s pension coverage is limited to the formal sector and coverage is low. More than 80% of those who live in rural areas are not covered. There is no social health insurance in Malawi and no social protection programs for the elderly. They rely on the help of their families since public long care services are poorly developed. Additionally, 30% of elderly women live with children whose parents died due to HIV/AIDS, increasing their burden. Joint efforts between government and NGOs is required to address the numerous challenges faced by the elderly in Malawi.

306 24-17

Global aging and role of young power in Romania

Cristina Mihaela Asavoaie

School of Social and International Studies, University of Tsukuba

Similar to other European countries, Romania is facing a period of drastic population aging which started later than the rest of Europe and has a slower rate of growth. In 2008, the percentage of people aged 65 and over was 14.9%, lower than the European Union average (17.1%), but it is expected that it would represent more than 30% of the population by 2050. Before 1989, Romania was a communist country with no legal abortion, where population growth was an important point of the government agenda. After 1989, birth rates declined, the external migration increased and the children born between 1968 and 1989 (the “decree 770” generation, as is known the baby boom based on policies that restrict abortion and contraception in Romania) are moving toward older ages. In present Romania, 15.4% of the total population is over 65, compared to 14.8% of children under 15. From an economic point of view, Romania does not have the resources to support this older population. The pension system, consisting of 3 providers: the state pension, the private mandatory pension and the optional private pension, may not be reliable due to these demographic changes. Community services are provided by law, but the implementation system is weak. A limited number of residential facilities and the insuffi cient capacity of day-care facilities do not cover the actual need. From a moral point of view, younger generations understand that taking care of older people is an undisputed duty. Sayings such as “If you wish good advice, consult an old man.” strengthen the respect for the elderly people, emphasizing their wisdom based on life experience. However, not all the needs are covered by moral standards in Romanian society. Therefore, older people are facing problems such as lack of economic support or health care, economic or social abandonment, abuse and neglect by their families. A solution to these problems can be found adapting global ideas to the Romanian society.

307 24-18

Aging in Russia

Taylor Quanan

School of Social and International Studies, University of Tsukuba

The focus of this abstract is to examine population trends in Russia and how that impacts the aging population. Russia is one of the few countries with a negative population growth rate. In 1991, the Soviet Union collapsed when the population was 148 million, followed by two decades of half a percent decline per year (700,000 people annually). The economic transition resulted in lower living standards and increased death rates and alcoholism. Today, Russia’s population is estimated at 143 million. The United States Census Bureau predicts that Russia’s current population will decline to a mere 111 million by 2050, representing more than a 20% decrease. Fertility is a universal determinant of population aging. Consequently, birthrates sharply declined. Decline in fertility relates to undesirable economic and political conditions. Fertility rates in Russia are among the lowest in the world. Russia has attempted to increase their population. In 2007, President Vladimir Putin implemented a new immigration policy in an attempt to fi ll labor shortages and maintain economic potential. However, when implemented, the population continued to decline and was not possible to be compensated through immigration. President Putin called for a 10-year program that relied heavily on increased allowances for women bearing children, particularly those who bear a second or third child and improvements in child-care benefi ts. It is quintessential to the success of Russia to revert the declining population. Demographers warned that population decline will eventually rob Russia of the labor force it needs to sustain major industries and maintain its aging infrastructure. Some experts predict that, by midcentury, the country’s population could fall below 80 million.

308 24-19

Principles and organization of the social security system for family care in Sweden

Natsumi Shimafuji

School of Nursing, University of Tsukuba

Sweden did not participate in the Second World War and it may be one of the reasons why aging began quite early compared to other countries. Sweden turned into aging society in the late 1880s and into an aged society in the 1970s. In 2013, the proportion of older persons reached 19.33% drawing near to becoming a super-aged society which present some challenges. In Sweden, it is common that both men and women work. The “Gender Inequality Index” positi oned Sweden as the fi rst among 146 countries, according “2011 Human Development Report” by the United Nations Development Program (UNDP). The index is composed of insurance systems, empowerment, and labor market. It shows the degree that the inequality of gender prevents the human development of the nation. In 2011, the “World Economic Forum” announced its “2011 Global Gender Gap Report (GGI)”. GGI shows the gender gap in the economic, educational, insurance and political fi elds. Sweden had the fourth place. In summary, Sweden is internationally recognized as a society with high gender equality. However, Sweden was previously a patriarchal society, where women had to do housework, child-rearing and care without remuneration. This trend has remained. Most family caregivers are women, the children of the elderly, 45-65 years old (potential workers). Balancing work and care is diffi cult, so modifi cations were made to allow part-time jobs or taking paid or unpaid vacations. However, since job positions are not guaranteed, the number of women who become full-time housewives is increasing. It is a future task for social policies to reduce the care work of the family and improve the conditions of women even more.

309 NOTE

310 25 Frontiers in Neuroscience

Monday, September 28 Venue: Convention Hall 300

Frontiers in Neuroscience

The brain is an important organ that acts as a center to regulate and integrate the functions of various organs in the human body. However, many mysteries still surround brain function. Six internationally renowned invited speakers introduce the latest knowledge in basic and applied neuroscience.

Session Organizers: Kosuke Kato, Tadachika Koganezawa

Chairs: Jackson C. Bittencourt, University of Sao Paulo Part One Masayuki Matsumoto, University of Tsukuba Shih-Kuo Chen National Taiwan University 10:15-10:40 Atypical feedback circuit from inner retina to outer retina: light adaptation through melanopsin Andrés Couve University of Chille 10:40-11:05 The endoplasmic reticulum and protein traffi cking in axons Jackson C. Bittencourt University of Sao Paulo 11:05-11:30 The twelve labors of MCH: a quarter of a century later Chairs: Philippe De Deurwaerdère, University of Bordeaux Part Two Hiroshi Yamada, Univerisity of Tsukuba Hiroshi Yamada Univeristy of Tsukuba 11:45-12:10 Context dependent value representations in Monkey ventromedial Prefrontal Cortex Neurons Philippe De Deurwaerdère Univeristy of Bordeaux 12:10-12:35 L-DOPA: from the antiparkinsonian pill to the psychostimulant drug Jeffrey L. Krichmar University of California, Irvine 12:35-13:00 Learning touch preferences with a tactile robot using dopamine modulated STDP in a model of insular cortex

311 25-1

Atypical feedback circuit from inner retina to outer retina: light adaptation through melanopsin

Po-Ting Yeh1, Nan-Fu, Liou1, Chi-Chan Lee1, Shi-Feng You1, and Shih-Kuo Chen1,2

1Department of Life Science; National Taiwan University 2Genome and Systems Biology Degree Program, National Taiwan University and Academia Sinica

The primary axons of retinal ganglion cells (RGCs) project to many brain regions to mediate various image-forming and behavioral functions. It is well known that RGCs provide unidirectional light information from the retina to the brain. Intriguingly, a small population of RGCs, most likely a subtype of melanopsin-expressing intrinsically photosensitive RGCs (ipRGCs), has intra-retinal axon collaterals that project toward the outer retina. The main axons from ipRGCs innervate many brain nuclei including suprachiasmatic nucleus for circadian photo-entrainment and olivary pretectal nucleus for pupillary light refl ex. Meanwhile, the intra-retinal axon collaterals from ipRGCs terminate at the inner-plexiform layer, a specifi c layer where RGCs receive synaptic input from other retinal neurons. However, the anatomical connection and functional role of ipRGC axon collaterals remain unclear. Here we show that axon collaterals originating from ipRGCs constitute an atypical feedback circuit to dopaminergic amacrine cells, conveying melanopsin signals from the inner to outer retina. In genetically ipRGC eliminated mice, dopamine-dependent b-wave light adaptation is abolished, which suggests that integrated light information from ipRGCs can be send bi-directionally to outer retina for light adaptation and to the brain for non-image forming functions. Our results illustrate the fi rst direct functional role for ipRGC axon collaterals and elucidate the neural circuitry and mechanisms underlying retrograde signal transmission from ipRGCs to infl uence retinal function.

312 25-2

The endoplasmic reticulum and protein traffi cking in axons

Andrés Couve

Program of Physiology and Biophysics, Institute of Biomedical Sciences (ICBM), Biomedical Neuroscience Institute (BNI), Facultad de Medicina, Universidad de Chile

Neurons are responsible for the generation and propagation of action potentials that constitute the fundamental mechanism for information transfer. They are large and polarized cells with dendrites and axons constituting their major functional domains. Axons are thin and long specializations that mediate the conduction of electrical impulses. Reg ulation of the axonal proteome is key to generate and mai nt ai n neu ral f u nction. Although fast and slow protein transports have been known for decades, newly identifi ed mechanisms to control the abundance of axonal proteins based on local biosynthesis and processing have emerged in recent years. We speculate that early secretory organelles in the axon provide a functional route for traffi cking and, in combination with local protein synthesis of membrane and secreted proteins, an alternative mechanism to regulate the axonal proteome. Using complementary in vitro and in vivo experimental models in rats and Drosophila we explore the presence and function of the endoplasmic reticulum and other early local secretory organelles in the axon. In Drosophila we investigate the role of neuronal atlastin in locomotion and axonal protein traffi cking. In mammalian peripheral neurons we evaluate the role of early secretory organelles in the delivery of sodium channels.

Funded by CONICYT USA2013-020, Fondecyt 1140617 and ICM P-09-015F.

313 25-3

The twelve labors of MCH: a quarter of a century later

Jackson C. Bittencourt1,2

1Laboratory of Chemical Neuroanatomy, Department of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo 2Center for Neuroscience and Behavior, Institute of Psychology, University of Sao Paulo

From the early days of the dual theory regarding the control of color changes in frogs and fi sh to its characterization in chum salmon and its discovery in mammals, the hypothalamic neuropeptide known as melanin-concentrating hormone (MCH) has been shown to play many roles. As originally described, the function of MCH was to turn fi sh skin pale, countering the effects of the alpha-melanocyte stimulating hormone (α-MSH). In the rat brain, MCH perikarya are located mainly in the lateral hypothalamic and incerto-hypothalamic areas, projecting to regions of the brain as varied as the olfactory bulb and the spinal cord. This suggests that MCH is involved in diverse brain functions, probably as a neuromodulator. In addition to its orexigenic role, MCH appears to be related to many other functions, including stress response, reproduction, certain aspects of motivated behavior, sensory perception, neuroendocrine responses, exploratory behavior, memory, learning, grooming, rearing, locomotor activity, and the sleep-wake cycle. Two MCH receptors have been described: MCHR1 (in rodents) and MCHR2 (in human and non-human primates). With some exceptions, MCHR1 distribution overlaps with that of MCH-immunoreactive fi bers. Nowadays MCH is also found outside of the rat central nervous system, in the periphery, for example: ovary, testicle, mammary gland and lymphocytes. The objective of this presentation is to describe the state of the art regarding MCH roles inside and outside the central nervous system. Supporting Agencies: FAPESP, CNPq, and CAPES

Keywords: feeding behavior; neuropeptides; hypothalamus, motivated behaviors

314 25-4

Context dependent Value Representations in Monkey ventromedial Prefrontal Cortex Neurons

Hiroshi Yamada

Division of Biomedical Science, Faculty of Medicine, University of Tsukuba

Neural correlates of value have been extensively examined in wide range of diverse brain regions in human and non human primate. It has been suggested that the orbitofrontal cortex (OFC) and ventromedial prefrontal cortex (vmPFC) is crucially involved in economic decision making. However, it is unclear how these value signals at the core of the decision circuits are dependent on behavioral contexts subject encountered. To address this issue, we recorded single neuron activity from medial area 14 (i.e. ventromedial prefrontal cortex, vmPFC) while monkeys performed a gambling task. During the behavioral task, monkeys chose either a “risky” or a “certain” option based on the values and reward probabilities associated with the options. While fi xating a central point, the monkeys received visual cues indicating the payoff magnitude of fl uid reward offered by two options located on the left and right sides. The payoff magnitude of risky options varied from trial-to-trial with a particular option ranging from 0 ml to 0.60ml in 0.06ml increments. The payoff magnitude varied with four different block structures; 0 to 0.24ml, 0 to 0.36ml, 0 to 0.48ml, and 0 to 0.60ml. On the other hand, the payoff magnitude of safe option was kept constant in each payoff magnitude blocks; 0.06ml, 0.12ml, 0.18ml, and 0.24ml. The probability that the risky option would yield a reward was fi xed at 50% across lotteries. After extensive training, the monkeys showed risk-neutral or slightly risk-averse behavior. Out of 102 vmPFC neurons, 22% and 35% represented the values of the risky option during and after decision-making, respectively. Two-thirds of these neurons showed a specifi c form of value coding in which neuronal activity was normalized by the range of possible reward outcomes recently encountered in each payoff block. Moreover, these normalized value signals were prominent only when monkeys are capable of choosing one option among alternatives freely, but diminished and almost disappeared when forced to choose one. Existence of the decision context-dependent normalized value signal in prefrontal network suggested this structure provide effi cient valuation signals for self-organized decisions.

315 25-5

L-DOPA: from the antiparkinsonian pill to the psychostimulant drug

Philippe De Deurwaerdère

Professor of Neuroscience and Neuropharmacology. University de Bordeaux

L-DOPA remains the best medicine in the treatment of Parkinson’s disease. After years of treatment, its effi cacy is impaired by motor disturbances such as dyskinesia and non-motor side effects such as psychosis. Recent behavioral and neurochemical studies have shown that serotonergic neurons play a pivotal role in the mechanism of action of L-DOPA in both the benefi t and the side effects. The mechanism of action enabling serotoninergic neurons to release L-DOPA-derived dopamine is still unclear.

Here, we aimed to address the changes of serotonergic neuron function after L-DOPA administration. We combined multisite intracerebral microdialysis and single unit extracellular recordings in the dorsal raphe nucleus in hemiparkinsonian rats.

L-DOPA (3-100 mg/kg, ip.) dose-dependently enhanced dopamine extracellular levels in the striatum, substantia nigra pars reticulata, hippocampus and prefrontal cortex. Such an effect was abolished in rats bearing a lesion of serotonergic neurons using 5,7-dihydroxytryp- tamin. L-DOPA (3-100 mg/kg, ip.) decreased unequally serotonin extracellular levels in the afore-mentioned brain regions. Strikingly, L-DOPA (12 mg/kg) did not modify the fi ring rate or pattern of serotonergic-like neurons recorded in the dorsal raphe nucleus. When focusing on serotonin release in the prefrontal cortex and the hippocampus, we found upon Ca2+ re- moval that L-DOPA (12 or 100 mg/kg) enhanced serotonin extracellular levels in both regions. Concomitantly, L-DOPA-stimulated dopamine release persisted partly in the absence of Ca2+ in a region-dependent manner. Local application of the serotonin reuptake inhibitor citalo- pram (1 μM) blunted the responses to L-DOPA (3-12 mg/kg) on dopamine extracellular levels mainly in the hippocampus. Systemic injection of citalopram (4 mg/kg) reduced the effects of L-DOPA (3 or 100 mg/kg) in all regions.

In conclusion, we show that the function of serotonergic neurons is disrupted by L-DOPA. The identifi cation of non-vesicular releases of serotonin and dopamine in L-DOPA’s effect recalls the mechanism of action of some psychostimulant drugs.

316 25-6

Learning touch preferences with a tactile robot using dopamine modulated STDP in a model of insular cortex

Ting-Shuo Chou2, Liam D. Bucci1, Jeffrey L. Krichmar1,2

1Department of Cognitive Sciences, University of California, Irvine 2Department of Computer Science, University of California, Irvine

Neurorobots enable researchers to study how behaviors are produced by neural mechanisms in an uncertain, noisy, real-world environment. To investigate how the somatosensory system processes noisy, real-world touch inputs, we introduce a neurorobot called CARL-SJR, which has a full-body tactile sensory area. The design of CARL-SJR is such that it encourages people to communicate with it through gentle touch. CARL-SJR provides feedback to users by displaying bright colors on its surface. In the present study, we show that CARL-SJR is capable of learning associations between conditioned stimuli (CS; a color pattern on its surface) and unconditioned stimuli (US; a preferred touch pattern) by applying a spiking neural network (SNN) with neurobiologically inspired plasticity. Specifi cally, we modeled the primary somatosensory cortex, prefrontal cortex, striatum, and the insular cortex, which is important for hedonic touch, to process noisy data generated directly from CARL-SJR’s tactile sensory area. To facilitate learning, we applied dopamine-modulated Spike Timing Dependent Plasticity (STDP) to our simulated prefrontal cortex, striatum and insular cortex. To cope with noisy, varying inputs, the SNN was tuned to produce traveling waves of activity that carried spatiotemporal information. Despite the noisy tactile sensors, spike trains, and variations in subject hand swipes, the learning was quite robust. Further, the plasticity (i.e., STDP) in primary somatosensory cortex and insular cortex in the incremental pathway of dopaminergic reward system allowed us to control CARL-SJR’s preference for touch direction without heavily pre-processed inputs. The emerged behaviors we found in this model match animal’s behaviors wherein they prefer touch in particular areas and directions. Thus, the results in this paper could serve as an explanation on the underlying neural mechanisms for developing tactile preferences and hedonic touch.

317 NOTE

318 26 International Workshop on Time-series Data Sonifi

Tuesday, September 29 Wednesday, September 30 Venue: Conference Room 403

International Workshop on Time-series Data Sonifi cation

Global phenomena that unfold in sequence are generally represented in the form of time series data. In this interdisciplinary workshop, we aim to establish a collaborative relationship among international researchers from various fi elds, to address the issues and problems that are commonly found in interfacing people and time-series data with sound, and to discover the exciting directions for future research in the fi eld. This session is supported by: Japanese Society for Sonic Arts (JSSA), IPSJ special interest group on Music and Computer (IPSJ-SIGMUS), International Community for Auditory Display (ICAD), and JST PRESTO “Information Environment and Humans.”

Session Organizer: Hiroko Terasawa Day 1 (9/29) Part One Chair: Yota Morimoto, Royal Conservatory of the Hague Hiroko Terasawa University of Tsukuba 10:00-10:10 Opening remarks David Worrall Fraunhofer-Institute for Integrated Circuits IIS 10:10-10:40 Using polymedia sonifi cation for digital network monitoring: The Netson project Masaki Matsubara University of Tsukuba 10:40-11:10 Takahiko Uchide AIST Interactive multiple seismic waves sonifi cation for data exploration 11:10-11:25 Break Visda Goudarzi University of Music and Performing Arts Graz 11:25-11:55 Data listening is hear! cation 12:00-13:00 Lunch Part Two Chair: Masaki Matsubara, University of Tsukuba Naofumi Aoki Hokkaido University 13:00-13:30 Sound programming using MATLAB 13:30-13:45 Break 13:45-15:15 Workshop session 15:15-15:30 Break 15:30-16:30 Performance: Grace Leslie All day Installation: NetSon project by David Worrall

319 Day 2 (9/30) Part Three Chair: David Worrall, Fraunhofer-Institute for Integrated Circuits IIS Singapore University of Technology and Design, and Grace Leslie 9:45-10:15 Massachusetts Institute of Technology Sonifi cation of EEG and Expressive Movement for Affective Neurofeedback Makio Kashino NTT Communication Science Laboratories 10:15-10:45 Sonifi cation of a player’s physical / mental states for sport training 10:45-11:00 Break Hiroko Terasawa University of Tsukuba 11:00-11:30 Auditory gestalt, interaction, and emotion: perceptual and cognitive issues in data sonifi cation of biological data Thomas Hermann University of Bielefeld 11:30-12:00 Levels of time and space in data exploration and interactive sonifi cation 12:00-13:00 Lunch Part Four Chair: Naofumi Aoki, Hokkaido University Yota Morimoto Royal Conservatory of the Hague 13:00-13:30 Sound design in sonifi cation 13:30-13:45 Break 13:45-15:15 Workshop session 15:15-15:30 Break 15:30-16:30 Performance: Brain dreams Music Project by .pf All day Installation: NetSon project by David Worrall

320 26-1

Using polymedia sonifi cation for digital network monitoring: The Netson project

David Worrall

Fraunhofer IIS International Audio Laboratories Erlangen Fraunhofer-Institute for Integrated Circuits IIS Erlangen, Germany

The increased complexity and sophistication of modern computer networks, and the explosive increase in the amount of data that these networks carry, present signifi cant challenges for network monitoring and exploration. Such large amounts of multivariate time-series data requires a new generation of tools and methods, including those that rely on human perception. As a technique, information perceptualization (principally visualization and sonifi cation) seeks to create ‘polymodal’ ways of intuitively conveying abstract information in algorithmically reproducible ways, to use sound and image representations and interactions to take advantage of the broad pathways between the brain and sensory organs to allow users to hear, see, explore and understand large amounts of information in intuitive ways. Like most mammals, humans have evolved as polymodal perceiving bodies. Sight and hearing, for example, are sensitive in different ranges of the frequency spectrum and can be used to attend to spatial and temporal information with different levels of discrimination. So, while our aural perception is clearly superior in certain types of time-series features such as differentiating temporal sequencing and frequency discrimination and better adapted to detecting movement in our surroundings, our visual perception is well suited to creating stable ‘scenes’ that assist us in understanding the spatial relationships between perceptual objects. The impetus for a polymodal approach comes from an understanding that while the separation of the senses can be useful for deconstructive analysis, and we still have a lot to learn about how to use them for detecting information in data, they do not work independently, and certainly not in isolation. Netson is a prototype perceptual monitoring tool that uses sonifi cation supported by visualization to display features of an organization’s digital network. Its pragmatic use is to assist people to peripherally monitor the activity of individual parts of a network - the ways in which they converge and interact - or of the network as a whole system. Because it is designed to induce a low cognitive load, this technique can be used by human monitors who are simultaneously engaged in other tasks. This presentation will include a demonstration and discussion of the sonifi cation and visualization of the live real-time data streaming from Fraunhofer ISS in Germany.

321 26-2

Interactive multiple seismic waves sonifi cation for data exploration

Masaki Matsubara1 & Takahiko Uchide2

1Laboratory for Sound and People with Computing, University of Tsukuba, Tsukuba, Japan 2Geological Survey of Japan, AIST, Tsukuba, Japan

Japan is widely known for earthquake country. National Research Institute for Earth Science and Disaster Prevention (NIED) provides seismic wave databases from the networks of various kinds of instruments and facilities (e.g., K-NET, KiK-net, Hi-net, and F-net). Because of 100 - 200 Hz of typical sampling frequencies, audifi cation of seismic waves at natural speed is hard to listen. Thus, traditional way to listen single seismic wave for monitoring application is to audify the waveform with high playback rate, which often makes the sound too fast to catch up the nature of earthquake rupture and seismic propagation. In this talk, we present an interactive multiple seismic waves sonifi cation method for data exploration and an example sonifi cation of the 2011 Tohoku earthquake waves propagating over Japan Islands using 116 seismic stations. The playback rate is just 10, therefore it is easy to understand the propagation of seismic waves. The sonifi ed sound shapes some characteristics and distributions so that seismologist can easily detect the time span and frequency band to be focused on. We will show how the seismologist explore the data with visualization and sonifi cation and how he discovered another induced earthquake with sonifi ed sound.

322 26-3

Data listening is hear!

Visda Goudarzi

University of Music and Performing Arts Graz, Austria

This talk explores some of the challenges on data-mining and sonifi cation in a data-intense domain such as climate science and examines how to facilitate new insights in data. The purpose of this talk is to elaborate an understanding of what data is as a concept, as a component in acquisition of knowledge, and as something that can be communicated between its source and its receiver in auditory form. Moreover it is essential within the scope of this symposium to evaluate methods of auditory presentations of datasets in the context of climate in a way that the climate scientists’ knowledge about features and patterns hidden in the data improves. Climate data is an ideal domain for a number of reasons including the typically large multivariate data sets, the dynamically changing nature of the data, and the nature and process of creating models. Climate science data is usually temporal, spatial, or spatiotemporal which makes it a perfect candidate for data mining and sonifi cation which are also spatiotemporal. While there is decades of research in climate statistics and applications of sonifi cation, systematic efforts in sonifi cation of climate statistics are rare. Some interesting aspects of data analysis that are interesting to explore are: how to deal with auto- or cross-correlations. Climate data are geographical and inherit the spatial or temporal correlation properties. Additional challenges in sonifi cation of climate data stem from nonlinear dependence, long memory processes in time, and long-range dependence in space.

323 26-4

Sound programming using MATLAB

Naofumi Aoki

Hokkaido University

Computer programming is an effective approach for understanding the mechanism of sound processing. This talk describes some techniques of sound programming using MATLAB.

324 26-5

Sonifi cation of EEG and expressive movement for affective neurofeedback

Grace Leslie1,2

1Singapore University of Technology and Design 2Media Lab, Massachusetts Institute of Technology

We present a new musical interface that maps expressive gesture to sound, designed to invite participants to affectively engage in the basic emotions. In its present form, the interface consists of a Leap Motion (www.leapmotion.com) device that tracks repeated small expressive gestures made by a participant’s hand. Concatenative synthesis software (Schwarz, D et al, Journées d’Informatique Musicale, 2008) translates these gestures into an expressive wash of sound by mapping the fi rst and second principal components of the recorded movement to the computed spectral centroid and periodicity of each sound segment selected for playback. A dry-electrode EEG system records EEG as the participant performs gestures corresponding to a basic emotion (anger, grief, joy, etc.). The artifact subspace reconstruction (ASR) method, as implemented in the BCILAB toolbox (Kothe, C.A., et al, Journal of Neural Eng 10(5), 2013) for Matlab, is used to remove local peak artifacts in the EEG data that arise from participant movement. The EEG accompanying each emotion state is classifi ed in real-time using a predictive model that estimates the probability of each state across short EEG data time windows, also implemented in the BCILAB toolbox. An ambient music engine cycles through textures and musical intervals composed to suggest and induce a spectrum of affective states (Makeig, S. et al, Springer Lect Notes in Comp Sci, vol. 6975, pp. 487-496, 2011). This project is informed by previous experiments (Leslie, G., et al, Psychomusicology 24(1), 2014) for which the fi rst author and colleagues developed a method for studying musical engagement using simple expressive rhythmic ‘conducting’ gestures matching a musical pulse, inspired by Manfred Clynes’ sentic cycles method (Clynes, 1977). This project attempts to clarify the role that expressive gestures can play in improving emotional health. If successful, the proposed musical system for affective neurofeedback may help those with mood regulation challenges, in serving as an adjunct to expressive movement and music therapy.

325 26-6

Sonifi cation of a player’s physical/mental states for sport training

Makio Kashino1,2,3

1NTT Communication Science Laboratories, NTT Corporation, Kanagawa, Japan 2Tokyo Institute of Technology, Kanagawa, Japan 3JST CREST, Kanagawa, Japan

Implicit (i.e., unconscious and automatic) sensory / motor / emotional processes play essential roles in sports. It is, however, diffi cult for a player to be aware of, or have voluntary control over, the implicit processes during the play. We have been developing methods to help players improve sport skills and optimize mental states by making the implicit processes explicit using body / mind-reading technologies and modulating the implicit processes through sensory feedback. I will introduce some examples, including a training system for baseball pitching based on sonifi cation of surface electromyographic (sEMG) signals monitored at some task-relevant muscles of a pitcher using real-time wireless measurement devices.

326 26-7

Auditory gestalt, interaction, and emotion: perceptual and cognitive issues in data sonifi cation of biological data

Hiroko Terasawa

Faculty of Library, Information and Media Science, University of Tsukuba

How can we make a sonifi cation intelligible? How can we establish a trustable, reliable, and emotional relationship between data and users? How can we superimpose multiple information within a sound? How can we formulate auditory gestalt according the patterns within data? Summarizing the 5 years biological-data sonifi cation research under JST PRESTO program, we explore such perceptual and cognitive issues with examples from the projects.

327 26-8

Levels of time and space in data exploration and interactive sonifi cation

Thomas Hermann

Ambient Intelligence Group, Cognitive Interaction Technology Cluster of Excellence (CITEC), Bielefeld University, Bielefeld, Germany

Time and Space are basic dimensions in which we organize experience, interaction, data and science. Sonifi cations, auditory representations of data are in substance sound and thus intrinsically ‘live’ in time, while many high-dimensional data are not organized in time. This talk focusses on the different relevant levels of time and space in exploratory data analysis and interactive sonifi cation. Selected application examples (EEG sonifi cation, Interactive Sonifi cation in sports, time series analysis, analysis of intrinsic data dimensionality and clustering of high-dimensional data) will make these levels more tangible (better: audible) and provide motivation for the approach of Model-based Sonifi cation that enables a principled decoupling of time in data and the user’s time, which is thus set free for immediate interaction with the sonic data representations.

328 26-9

Sound design in sonifi cation

Yota Morimoto

Institute of Sonology, Royal Conservatory, The Hague, the Netherlands

The author examines time-honoured techniques of electronic music production and design of commercial synthesizers in light of their potential usefulness for sonifi cation and auditory display projects. Particularly, the practice of sound design in voltage-controlled studios and analog synthesizers (i.e, that which makes use of VCOs, VCFs, VCAs and Envelope Generators) is discussed in relation to the reviving trend in analog synthesis. While it remains reasonable to employ digital tools in sonifi cation, a number of observations relevant to sound design in auditory display projects can be made. In order to verify the above, the author uses a sonifi cation software library implemented in SuperCollider, an open-source cross-platform programming environment for sound synthesis and music composition. Its key features have been shaped over the course of different projects (with cardiologists, seismologist and a motor company) and thus aim at covering different scenarios of auditory display. The fi rst of which is simplifi cation of common tasks involved in sonifi cation (e.g, data handling, fi le i/o, parameter mapping, etc.); the second, a unifi ed interface to both realtime and non-realtime data handling; and the last, programmatically generated sound synthesis templates. How the software library directs a workfl ow draws close relevance to the above practice of electronic music production. However, a number of useful functionalities possible with digital tools and other modern sound synthesis techniques are also implemented.

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330 27

Monday, September 28 Current Research of the Local Meteorology Related to the Issue of Renewable Energy and Urban Climate Venue: Conference Room 403 Current Research of the Local Meteorology Related to the Issue of Renewable Energy and Urban Climate

Studies of local meteorology contribute to a wide variety of scientifi c and social issues, such as weather forecasts for wind-power generation and heat island researches. In this session, we will discuss topics from basic reseach such as local wind and local meteorology model, to applied research such as prospect of wind-power generation and heat island.

Session Organizer: Hiroyuki Kusaka

Part One Chair: Hiroyuki Kusaka, University of Tsukuba Jason Knievel National Center for Atmospheric Research 14:15-14:55 Downslope winds, from gentle to violent Yu-bao Liu National Center for Atmospheric Research 14:55-15:35 NCAR real-time four dimensional data assimilation (RTFDDA): technologies and applications George Bryan National Center for Atmospheric Research 15:35-16:15 Simulations and observations of wind speed in the boundary layer of tropical cyclones. Chuan-yao Lin Academia Sinica 16:15-16:45 An improved urban canopy model and its application on future climate study over Taiwan Fujio Kimura University of Tsukuba Panel Discussion: Numerical studies on the local meteorology contribute to the planning of renewable energy supply, such as solar panels and wind-power generators. Microscale atmospheric numerical models contribute also to the problems in heat island effects, and how it affects climate change in the near 16:45-17:15 future. In this session, we are going to discuss the following problems and solutions: • Predictability of the abrupt change in wind velocity • Uncertainty in the atmospheric prediction for small scale phenomena • Modeling of the microscale atmospheric process

331 27-1

Downslope winds, from gentle to violent

Jason C. Knievel

Research Applications Laboratory National Center for Atmospheric Research

Wind is accelerated down sloped terrain in many atmospheric phenomena around the world. Slopes range from slight to steep. Downslope winds range from gentle to violent. They infl uence many sectors of society, including health, transportation, agriculture, renewable energy, and human settlement itself. Many of these infl uences are due to the aggregate effects of recurrent downslope winds that, over time, are a key attribute of a local climate. For wind energy, as an example, it is important to study the long-term statistics of downslope winds, not just individual cases. Some processes that force downslope winds are local, other processes are mesoscale or synoptic. Often forcing occurs on a variety of scales that interact in complex ways. It is not surprising, then, that downslope winds can be challenging for numerical models. Despite the challenge, models are very useful tools for understanding the dynamics of downslope winds and for predicting when and where they will occur. This presentation will offer an overview of many varieties of downslope winds. The processes responsible for downslope winds will be described using theory, observations, and numerical simulations. There will be examples of numerical simulations that are successful and that are not successful. Unsuccessful simulations can help us understand where model developers should focus attention to improve modeling of wind in complex terrain. Because downslope winds are local, often brief, and closely tied to terrain elevation, it would be natural to guess they might not be strongly affected by global climate change, but that is unclear. This presentation will include speculation on how climate change might alter the characteristics and frequency of downslope winds in some locations.

332 27-2

NCAR Real-time Four Dimensional Data Assimilation (RTFDDA): Technologies and applications

Yubao Liu

National Center for Atmospheric Research

Many applications require accurate high-resolution local-scale weather analysis, now- casting, and short-term forecasting, as well as regional micro-climatology. Over the last 10 years, an advanced mesoscale and microscale weather modeling system specifi cally toward addressing these needs has been developed at the Research Application Laboratory of NCAR ( R A L/ NCA R). T he modeli ng system consist s of t he NCA R W R F-A RW, a suite of adva nced d at a assimilation technologies, an observation data processing suite, and innovative model output statistical post-processing tools procedures. The model system has been implemented and customized for over 40 regional applications in the U.S. and international regions, supporting various missions by the U.S. governments, private industries and international organizations. Research and development to refi ne and improve the system accuracy and service abilities have been continuing, and new emerging modeling technologies are incorporated. The major capabilities of the system include multi-scale, rapid-update, high-resolution deterministic and mesoscale ensemble 4-D probabilistic data assimilation analysis and forecasting, LES- scale microscale data assimilation and forecasting, and reconstruction of microclimatology with 4-D continuous data assimilation technology. The FDDA scheme allows effectively and effi ciently assimilating all weather observations into a modifi ed WRF model to generate multi- year dynamically balanced, physically consistent and cloud/precipitation spun-up meso- and micro-scale weather analysis.

333 27-3

Simulations of wind speed in the boundary layer of tropical cyclones

George H. Bryan

National Center for Atmospheric Research

Over the past 10 years, a numerical modeling system called CM1 (“Cloud Model version 1”) has been developed at NCAR to study extreme phenomena such as hurricanes, tornadoes, and severe convective wind gusts. Some of the key numerical techniques of CM1 will be described in this presentation, such as the time-integration scheme, advection scheme, and boundary conditions. As an example application of CM1, results will be shown from simulations of the tropical-cyclone boundary layer, which is the roughly 1-km-deep layer above the ocean surface. A simple and inexpensive method, which specifi es the large-scale advection of angular momentum by the secondary circulation of a tropical cyclone, can accurately reproduce several bulk measures of the tropical-cyclone boundary layer (such as boundary-layer depth of ~1km and a surface infl ow angle of ~25 degrees). A more complex and expensive method, which simulates the entire inner core of a tropical cyclone, produces a broader perspective on the effects of turbulence in a tropical cyclone. In particular, wind-speed variance maximizes in the lowest km of the atmosphere just inward of the radius of maximum winds, consistent with observational studies.

334 27-4

An improved urban canopy model and its application on future climate study over Taiwan

Chuan-Yao Lin1*, Chiung-Jui Su1, Hiroyuki Kusaka2, Yuko Akimoto2, and Yang Fan Sheng1

1Research Center for Environmental Changes, Academia Sinica, Taiwan 2Center for Computational Science, University of Tsukuba

This study evaluated the impact of urbanization over northern Taiwan using the Weather Research and Forecasting (WRF) model coupled with the Noah land-surface model and a modifi ed Urban Canopy Model (WRF-UCM2D). In the original UCM coupled in WRF (WRF-UCM), when the land use in the model grid net is identifi ed as “urban”, the urban fraction value is fi xed. Similarly, the UCM assumes the distribution of anthropogenic heat (AH) to be constant. Such not only may lead to over- or underestimation, the temperature difference between urban and non-urban areas has also been neglected. To overcome the above-mentioned limitations and to improve the performance of the original UCM model, WRF-UCM is modifi ed to consider the 2-D urban fraction and AH (WRF-UCM2D). The two models were found to have comparable simulation performance for urban areas but large differences in simulated results were observed for non-urban, especially at nighttime. WRF-UCM2D yielded a higher R2 than WRF-UCM (0.72 vs. 0.48, respectively), while bias and RMSE achieved by WRF-UCM2D were both signifi cantly smaller than those attained by WRF-UCM (0.27 and 1.27 vs. 1.12 and 1.89, respectively). In other words, the improved model not only enhanced correlation but also reduced bias and RMSE for the nighttime data of non-urban areas. WRF-UCM2D performed much better than WRF-UCM at non-urban stations with low urban fraction during nighttime. The improved simulation performance of WRF-UCM2D at non-urban area is attributed to the energy exchange which enables effi cient turbulence mixing at low urban fraction. In this study, we have also performed dynamic downscaling of Taiwan’s future climate by using this WRF-UCM2D model. The simulations are forced by the Max Plank Institute Hamburg, global model, ECHAM5/MPIOM and Geophysical Fluid Dynamics Laboratory (GFDL) -High-Resolution Atmospheric Model (HiRAM). The achievement of this study has a crucial implication for assessing the impacts of urbanization on air quality and regional climate.

335 NOTE

336 28 Frontier Science on Transcription and Metabolism

Wednesday, September 30 Venue: Conference Room 304

Frontier Science on Transcription and Metabolism

Our aging society and resulting imbalance of the population structure is a global issue. Since metabolism and aging are intimately related, it is critical for us to understand normal metabolic pathways and mechanisms, in order to defi ne the key factors that are responsible for “healthy aging.” In this session, invited lecturers will present six individual research topics in fi elds related to “Transcription” and “Metabolism.” This session is being held for young scientists/students to learn cutting-edge research and to have an open discussion to learn how to build a career as an advanced researcher.

Session Organizer: Hiromi Yanagisawa

Part One Chair: Akiyoshi Fukamizu, University of Tsukuba 14:15-14:20 Greetings Wataru Kimura University of Tsukuba 14:20-14:40 Oxidative stress and cell cycle regulation of cardiomyocytes Yuta Takahashi University of Tsukuba 14:40-15:00 Targeted epigenome editing in human pluripotent stem cells Jiemin Wong East China Normal University 15:00-15:25 Dynamic Histone Crotonylation: Enzymes and Function in Transcription 15:25-15:35 Q&A

15:35-15:45 Coffee break Part Two Chair: Hiromi Yanagisawa, University of Tsukuba Jean-Michel Fustin Kyoto University 15:45-16:10 m6A mRNA methylation is coupled to transcription but enhance dynamic changes in mRNA levels Jenny Hsieh University of Texas Southwestern Medical Center 16:10-16:35 Deciphering transcriptional gene networks in adult neural stem cells Benjamin Tu University of Texas Southwestern Medical Center 16:35-17:00 Metabolic drivers of gene expression 17:00-17:10 Q&A

17:10-17:30 Career Session

337 28-1

Oxidative stress and cell cycle regulation of cardiomyocytes

Wataru Kimura1,2 and Hesham A. Sadek2

1Life Science Center, Tsukuba Advanced Research Alliance, University of Tsukuba 2Department of Internal Medicine, Division of Cardiology, University of Texas Southwestern Medical Center at Dallas

Heart failure is one of the most devastating diseases with high mortality rates, mainly because of the inability of the adult mammalian heart to regenerate damaged myocardium. Although limited myocyte turnover occurs in the adult heart, it is clearly insuffi cient for restoration of contractile dysfunction following injury. In contrast, the early postnatal mammalian heart is capable of signifi cant regeneration mediated by proliferation of preexisting cardiomyocytes, which is comparable with the regenerative potential of adult zebrafi sh or new hearts. However, mammals lose their capacity to regenerate the damaged heart shortly after birth, which is coincide with the permanent cell cycle exit of cardiomyocytes. The mechanism behind this permanent cell cycle arrest in postnatal cardiomyocyte has remained to be elusive. In the current study, we have shown that the transition from embryonic to postnatal circulation, which drastically changes the oxygenation state of cardiomyocytes, induces cardiomyocyte cell cycle arrest. We showed that there is a metabolic shift from glycolytic to oxidative metabolism in cardiomyocyte within a few days after birth, causing a marked increase in mitochondrial ROS that activates cell cycle checkpoint (Cell 157, 565-579, 2014). These fi ndings indicate that high rates of oxidative phosphorylation are not compatible with proliferative competency, and therefore we postulated that a population of proliferative cardiomyoctyes in the adult heart remains to be hypoxic and protected from oxidative stress. To verify this hypothesis, we generated a transgenic mouse where the Cre protein is stabilized under hypoxia to trace the linage of hypoxic cells. Our lineage tracing identifi ed a rare population of hypoxic cardiomyocytes that contributes to cardiomyocyte turnover in the adult heart (Nature 523, 226-230, 2015). These studies will allow us to characterize these proliferative cardiomyocytes, which will serve as a platform for future strategies to reactivate the endogenous regenerative capacity of the adult heart.

338 28-2

Targeted epigenome editing in human pluripotent stem cells

Yuta Takahashi1,2 and Juan Carlos Izpisua Belmonte1

1Salk Institute for Biological Studies 2Life Science Center, Tsukuba Advanced Research Alliance, University of Tsukuba

DNA methylation (5-methyl-cytosine) plays a major role in defi ning cell identity and function during both embryogenesis and adult physiology. Our understanding of how aberrant DNA methylation patterns contribute to different human maladies has been severely hampered by the absence of technologies able to modify DNA methylation at predetermined genomic loci. Here we describe novel methodologies for DNA methylation editing at targeted genomic loci through homologous recombination (HR) in human pluripotent stem cells. As a proof of concept, we induced targeted de novo DNA methylation at the MLH1 (a cancer related locus) promoter through HR to establish epimutation model in human embryonic stem cells. Additionally, to explore the potential therapeutic application of this strategy, we targeted an imprinting disease, Angelman syndrome (AS). We demonstrate complete and stable correction of aberrant DNA methylation in AS derived induced pluripotent stem cells (iPSCs), followed by restored expression of the AS-causing gene, UBE3A, in iPSCs derived dopaminergic neurons. The targeted and stable epigenome targeting strategies described here may help accelerate studies on basic principles underlying DNA methylation biology, as well as improve our understanding of how dysregulation of this epigenetic process leads to various human diseases, including imprinting disorders and cancer.

339 28-3

Dynamic Histone Crotonylation: Enzymes and function in transcription

Jiemin Wong

Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University

It has been well documented that histone lysine acetylation plays critical roles in regulation of transcription, DNA repair and replication. Recent studies indicate that, in addition to acety- lation, histones are also subjected to other types of acylation including propionylation, butyry- lation, succinylation and crotonylation. Furthermore, these modifi cations are likely catalyzed by the same family of enzymes such as CBP/p300, raising the questions as to whether these modifi cations share common or unique functions in transcription and other processes. We have systematically identifi ed and characterized the mammalian enzymes that catalyze his- tone/non-histone crotonylation and de-crotonylation. To dissect the function of crotonylation from acetylation, we have generated specifi c CBP/p300 mutants that are defective in catalyzing acetylation but are competent in catalyzing crotonylation. Functional assays indicate these mu- tants are capable of enhancing transcription activation by multiple transcription factors tested, suggesting that histone crotonylation is suffi cient to support transcription. Furthermore, we have generated a HDAC1 mutant that is defective in deacetylation but is capable of decroto- nylation. Functional assays indicate this HDAC1 mutant maintains a transcriptional repression function. Together our data provide compelling evidence that dynamic histone crotonylation is likely to be critically important for transcriptional regulation.

340 28-4

m6A mRNA methylation is coupled to transcription but enhance dynamic changes in mRNA levels

Jean-Michel Fustin and Hitoshi Okamura

Kyoto University Graduate School of Pharmaceutical Sciences, Department of Systems Biology

Messenger RNAs carry genetic information directing protein synthesis during translation, a process that also requires ribosomal and transfer RNAs, and is regulated by antisense RNAs. Translation can thus be seen as the convergence of all RNA species produced in a cell. Originally, the function and stability of various RNAs was believed to be solely the results of its nucleotide sequence, but rapidly posttranscriptional RNAs modifi cations, the most common being methylations, were identifi ed in rRNA, tRNA and in the cap structure of mRNA, which were found to regulate RNA stability and folding, cellular localization, exonucleases inhibition, translation and more. The advent of next generation RNA sequencing has provided an opportunity for a more precise analysis of the locations of roles of RNA methylation. Thanks to this, internal N6-adenosine methylation (m6A) was recently re-discovered in mRNA, previously believed to be contaminating nucleotides from rRNA. Evidence for a physiological function of m6A has so far been lacking, however. In 2013, we reported that m6A was a circadian pace-setter, that is, m6A was required for appropriate oscillations of circadian clock gene expression, by regulating the stability and nuclear export of clock gene transcripts (Fustin et al., 2013). We now report that m6A is coupled to transcriptional activity and enhance dynamic changes in transcript levels.

341 28-5

Deciphering transcriptional gene networks in adult neural stem cells

Jenny Hsieh

Department of Molecular Biology, University of Texas Southwestern Medical Center

Defi ning the transcriptional circuitry controlling neural stem cells is critical for harnessing the potential of adult neurogenesis in regenerative medicine. We have systematically dissected the function and mechanisms of individual transcriptional factors and epigenetic regulators that function in the stepwise progression of quiescent neural stem cells to mature dentate granule neurons in the adult hippocampus. Using a combination of conditional knockout mice to perform genetic loss-of-function and neural stem cell cultures to perform molecular and biochemical analysis, we have characterized a negative regulator of quiescent and activated stem/progenitor cells (NRSF/REST) and its co-repressors (class I histone deacetylases) to be important in maintaining the stem cell pool and preventing precocious activation of the neuronal lineage program. Furthermore, we have taken advantage of a reversible in vitro model of quiescence to identify the direct downstream targets of NRSF/REST involved in maintaining quiescent and proliferating stem cell populations. Our data suggest that NRSF/ REST binds and silences the neurogenic gene program to prevent precocious differentiation and maintain stemness. We also uncovered a set of non-neuronal gene targets, such as ribosomal and metabolic genes, important for stem cell quiescence. Our results provide mechanistic insight for strategies to promote the adult neural stem cell pool towards preventing age-related cognitive decline.

342 28-6

Metabolic drivers of gene expression

Benjamin P. Tu

Department of Biochemistry, University of Texas Southwestern Medical Center

Organisms must be able to rapidly alter gene expression in response to changes in their nutrient environment. Emerging evidence suggests that sentinel metabolites play very under- appreciated roles in the regulation of gene expression, and that particular epigenetic modifi cations of chromatin may have evolved specifi cally to enable the regulation of gene expression in tune with the metabolic state of the cell. My talk will discuss our efforts to understand how the expression of different classes of genes is coordinated with metabolism and cellular metabolic state.

343 NOTE

344 29

Monday, September 28 Survival Strategy in Arid Land: Management of Water Resources and Agriculture Venue: Conference Room 402 Survival Strategy in Arid Land: Management of Water Resources and Agriculture

On the outskirts of the Sahara located in the north of the African continent, agriculture has been managed with limited amount of water resources. Furthermore, severe drought in the future is expected due to global climate change. Under such situation, in order to develop the local area sustainably, advanced technology and local conventional technologies have to be combined to adapt agricultural activities to the natural and social environment. This session invites speakers from Tunisia and Mauritania to discuss the actual state of water resources and agriculture, and the ways they ought to be in the future.

Session Organizers: Mitsuteru Irie and Kenichi Kashiwagi Opening Hiroko Isoda University of Tsukuba 14:15-14:30 Opening Remark Director of ARENA Mitsuteru Irie University of Tsukuba 14:30-14:45 Introduction of the session Alliance for Research on North Africa Part One Chair: Mitsuteru Irie, University of Tsukuba Jamila Tarhouni Institut National Agronomique de Tunisie (Tunisia) 14:45-15:15 The agricultural practices in the region of Kebili and threat Centre de Recherches et des Technologies des Eaux Mohamed Kefi Technopole de Borj-Cédria (Tunisia) 15:15-15:45 Assessment of irrigation performance in the Lebna-irrigated perimeter in Tunisia Part Two Chair: Kenichi Kashiwagi, University of Tsukuba Institut Supérieur d’ Enseignement Technologiques Cherif Ould Ahmed de Rosso (Mauritania) 16:00-16:30 Survival strategy in arid land: Management of water resource and agriculture in Mauritania Erina Iwasaki Sophia University 16:30-17:00 Management of water resource and agriculture in the Senegal River area (Mauritania): Interdisciplinary study of farmers’ strategy Closing Kenichi Kashiwagi University of Tsukuba 17:00-17:10 Closing Remark

345 29-1

The agricultural practices in the region of Kebili and threat

Jamila Tarhouni

National Agronomical Institute of Tunisia

In the “almost island” of Kebili, due to the over-pumping of groundwater (200%), the piezometric level and the energy cost increase continually; in fact, the yearly total pumped water volume, both for irrigation as well as for urban use, is estimated at 400,000 m3 while the sustainable pumping volume should not exceed 173,000 m3/year. The decrease of the piezometric level resulted in many negative impacts such as deepening of wells, illicit drilling of private wells, salinization of soils and water, hydromorphic soils and water losses. To reduce the water pumping and to limit the water losses, deep irrigation techniques were introduced instead of traditional ones using open channels and furrows; unfortunately, this was at the origin of the decrease in the air humidity and tow new problems raised: the proliferation of diseases as well as a poor quality of dates. Another major problem that is very widely recognized is related to agricultural land fragmentation as limiting factor for agricultural development, for crop diversifi cation and water resources management; indeed, nearly 80% of the agricultural parcels have less than 1 ha as surface and the farmers cultivate mainly dates (Deglat Ennour variety) that present 90% of the production at Kebili. The practice of monoculture has caused the loss of biodiversity: - A monoculture of Deglat is very sensitive to diseases (fusariose vasculaire), to marketing problems and to the lack of manpower, - A genetic decline in fruit species due to an extended selection on several centuries with a remarkable adaptation to the environment, - A simplifi cation of the composition by species and varieties of the lower cultural fl oor, - An accelerated disappearance of several species of pastoral in the surrounding areas, Besides the losses of soils, of water resources and of biodiversity, the area is threatened by the land cover degradation due to several factors: - Wind erosion and movement of dunes along the Jerid Chott; - Wind and water erosion over the chains of Segui-Chareb -Tebaga and Dhahar; - Wind erosion on the Oriental Erg. Following the continuous decline of the piezometry and the environment degradation, the farmers have been faced with many diffi culties and profound changes have taken place. More specifi cally, the small farmers have become much more vulnerable because they have been severely disadvantaged by the lack of means to deepen wells or to drill new wells, to introduce new irrigation techniques and to invest in the restoration of their oasis. On the contrary, there are a growing number of large private farms which operate outside the regulatory compliance, which constitutes a threat to the sustainable oasis ecosystems. As consequences, we note the gradual disappearance of smallholder agriculture as well as negative impacts on society and the environment. The small farmers can no longer be suffi cient for their activities, are working as day laborers among the new major operators and are driven to seek their income sometimes far from agricultural sector. The Oasis systems whose undeniable durability on several successive generations is put to the test since the most recent decades, will - it disappear by the depletion of water resources and the reduction of the place and functions of peasant agriculture food?

346 29-2

Assessment of irrigation performance in the Lebna-irrigated perimeter in Tunisia

Mohamed Kefi 1, Kenichi Kashiwagi2, Atsuchi Kawachi3, Marwa Douma1,4, Slaheddine Khlifi 4, and Mohamed Ben Amor1

1Laboratory of Natural Water Treatment, Water Research and Technologies Centre (CERTE), Tunisia 2The Alliance for Research on North Africa (ARENA), University of Tsukuba 3Faculty of Life and Environmental Sciences, University of Tsukuba 4Ecole Supérieure des Ingénieurs de l’Equipement Rural, Tunisia

Water is the most important substance on earth. It is necessary for all living organisms and it is a prominent factor for all economic activities especially in agriculture. Due to climate change and to rainfall irregularity in time and space in arid and semi-arid areas in particular, water resource is becoming scarce. Water shortage increases problems of agricultural production. In fact, the major challenge of the Tunisian government is to encourage irrigation while preserving water at the same time. For this reason, the main objective of this study is to monitor the irrigation performance of the irrigated perimeter of GDA Lebna Dam in Tunisia. The approach applied is based on the application of remote sensing and geographic information systems (GIS) tools and data combined with CROPWAT software in order to estimate crop water requirement. Moreover, the main classes of land use map of the study area are identifi ed which is useful to monitor water crop needs. Through the implementation of some factors such as water use, crop type and farm size, Principal Component Analysis (PCA) was conducted to determine the main typologies of farms. Finally, evaluation of the irrigation performance between irrigation water requirement and water allocation showed that the water supplied is greater than the water required. This study can be helpful for the decision makers to adopt strategies to increase the effi ciency of irrigation systems and to a better irrigation scheduling which may lead to limit water excess and to save money. In the case of water scarcity, the estimation of accurate water demand combined with suitable agricultural extension services will increase the farmers’ awareness on water preservation.

347 29-3

Survival strategy in arid land: Management of water resource and agriculture in Mauritania

Cherif Cherif Mahmed1 and Mitsuteru Irie2

1Institute of Science and Technology (ISET) 2Soil Science Laboratory, Department of Plant Production and Protection

Underdeveloped countries are straddled with inadequate water supply and problems associated with its management. This situation has put a huge restriction on the economic use of water for irrigation, thus affecting food security. Nevertheless, ironically, unmanaged excess of water are emptied into the sea during the wet season. Water use is increasing faster than it can be produced. Moreover, this has put extreme pressure on the limited water for various uses such as industrial use, increasing urbanization, agricultural production, etc. Agricultural production is the biggest industry in developing countries. However, it receives just a little fraction of the water supply. This phenomenon has forced the industry to produce food under capacity, making developing countries food dependent. Identifying water sources, its production and its effi cient management underlines one important way to ensuring sustained food security in Mauritania. Erratic rainfall has been the bane of the Mauritanian economy and its food production. Thus, in Mauritania, it is of immense interest to examine the production of water and devise a plan of action to solving both food and water problems, which are related. The Mauritanian government strategy has engaged to utilize 137,000 hectares of arable land; of which 125,000 hectares are located in the Senegal River. However, at present, less than 30,000 hectares are in use annually. Additionally, the Ministry of Agriculture has increased irrigation land to about 50,000 hectares and 230,000 hectares in the rain-fed agriculture to make it possible for intensive farming to reach a total production in the range of 430,000 tons. Most of this rehabilitation and extension activities take place around the Senegal River Valley region, where agricultural production is concentrated (Campagne Agricole, 2015-2016). The support of agricultural inputs of fertilizers and pesticides during this campaign reached 65% per hectare (cooperatives) and 40% (private). La Maîtrise de L’eau has been selected by the Ministry of Agriculture to ensure that deprived regions have good, potable water; for preservation of the environment; to modernize agriculture to improve standards of living and to harness agricultural resources to raise production around the Senegal River. This presentation seeks to examine the present nature of supply of water and its distribution. It also examines parcels of land capable of producing food under irrigation in Mauritania. This is because it has a direct positive impact on crop production, especially cereals in Mauritania.

348 29-4

Management of water resource and agriculture in the Senegal River area (Mauritania): Interdisciplinary study of farmers’ strategy

Erina Iwasaki1, Yuki Maruyama2, Bouya Ahmed Ould Ahmed3, Mitsuteru Irie4

1Faculty of Foreign Studies, Sophia University 2Graduate School of Life and Environmental Sciences, University of Tsukuba 3Institut Supérieur d’ Enseignement Technologiques de Rosso 4Alliance for Research on North Africa

Mauritania is located in an arid region. Its population is about three million, but its area is three times larger than Japan of which 90 percent is desert. However, there is abundant water along the Senegal River area. Water is provided from Senegal River and its branch river Gorgol. There is also rainfall in summer. It is the only area in Mauritania suitable for agriculture. For this reason, the Senegal River area has been the focus of government projects supported by international organizations such as the World Bank and the African Development Bank. At the national level, these projects aim at securing the food supply, and at the household level in improving the living standards of the residents who are said to be under severe living conditions. The aim of this presentation is to provide some insights on the household strategies in the Senegal River area, based on research conducted under the project titled “Towards farmland development along the Senegal River in Mauritania - Flood control and traditional customs of water resource management” funded by Toyota Foundation from 2014 to date. The main fi eld sites are the Rosso area and Foum Gleita. In these two areas, we have been conducting a far mers’ survey by questionnaire. At present, 250 farmers have been interviewed. The questionnaire is composed of various questions regarding farmers’ behavior on water management, water and agricultural cooperatives, cultivation, and some socioeconomic situation of the farmers. The area is an interesting site for the study of the ecosystem that is closely linked to the social and cultural system. The area is characterized by the presence of residents living by farming and residents who specialized in animal husbandry. Most of them were originally nomads who recently settled. As to the cultural aspect, the area has different ethnicities such as Arab, Wolof, and Soninke, etc. Thus, by studying the social structure of this area, we may develop our understanding on the coexistence between humans and the environment (water), between people of different cultural and historical backgrounds, and between the central government and locals.

349 NOTE

350 30 University of Tsukuba Overseas Alumni Conference 2015

Wednesday, September 28 Venue: Conference Room 404

University of Tsukuba Overseas Alumni Conference 2015

This is the fi rst annual alumni conference, consisting of two parts, in which repre- sentatives from nine countries/regions will attend. Part One is a general meeting between university offi cials and the regional representatives. In Part Two, nine representatives also present their “learning and career development” as Tsukuba alumni.

Session Organizer: Tsuyoshi Kimura Part One Chair: Osamu Ohneda, University of Tsukuba Osamu Ohneda University of Tsukuba 10:15-10:25 Opening Remarks Caroline Benton University of Tsukuba 10:25-10:35 Greetings by the Vice President (International Affairs) Regional Representatives 10:35-11:40 Presentations and Discussions Tsuyoshi Kimura University of Tsukuba 11:40-12:00 Introduction of Overseas Alumni Database System Kyosuke Nagata University of Tsukuba 12:00-12:15 Greetings by the President Part Two Chair: Tsuyoshi Kimura, University of Tsukuba ˂ Theme ˃ Learning at the University of Tsukuba and my career development Presenters: (1) Nguyen Hoang Oanh, Vietnam Japan University (VJU), Vietnam 14:15-15:00 National University (Vietnam) (2) Hua-Wei Lin, President, National Taiwan University of Sport (Taiwan) (3) Cheng Yongqiang, Professor, China Agricultural University (China) (4) Muhamad Askari, Senior Lecturer, Universiti Teknologi Malaysia (Malaysia) (5) Adrian Witt, Student (Faculty of Arts, Asian Studies, Japanese Studies), 15:15-16:00 University of Bonn (Germany) (6) Shimako Kawauchi, Associate Project Scientist, University of California, Irvine (USA) (7) Yaya Suryana, Electromedic System Program Director, BPPT (Agency for the Assessment and Application of Technology) (Indonesia) (8) Kalykova Gulnaz, Manager, Wellness Center of Massimov LLP 16:15-17:00 (Kazakhstan) (9) Mohamed Kefi , Assistant Professor, Centre de Recherches et des Technologies des Eaux Technopole de Borj-Cédria (Tunisia) Osamu Ohneda University of Tsukuba 17:00-17:15 Closing Remarks

351 NOTE

352 31 AEARU Young Researchers International Conference

Monday, September 28 Tuesday, September 29 Venue: Conference Room 304/402

AEARU Young Researchers International Conference

The conference will be held under the theme of “Transmission, Preservation and Applications of Culture in the East Asian Region.” In East Asia, cultures have been generated, transmitted and shared in the course of history. Culture rooted in each region is fused, integrated, and shared – developing its own uniqueness while maintaining some common characteristics. Appreciation of cultural diversity and similarity in the East Asian region can lead to deeper understanding of the values of people and society that can build mutual respect and friendship. Culture brings joy and enriches the lives of people; thereby culture has the power to stimulate society. We trust that this conference can serve as an opportunity to establish future collaboration in these subject fi elds among young researchers in the East Asian region through the intellectual exchange of research reports and studies.

Session Organizer: Chiho Kabeya Day 1 (9/28) Venue: Conference Room 304 10:15-13:00 Keynote Speech and Oral Presentations

13:00-14:00 Lunch

14:00-17:15 Oral Presentations Day 2 (9/29) Venue: Conference Room 402 9:00-12:00 Short Oral Presentations and Discussions

12:00-13:00 Lunch

13:00-17:00 Free to attend other TGSW sessions you are interested in Day 3 (9/30) Whole-day One-day trip to experience Japanese Culture

353 NOTE

354 32 3rd International Conference for the Global Innovation Joint-Degree Program

Wednesday, September 30 Venue: Conference Room 402 3rd International Conference for the Global Innovation Joint-Degree Program

This international conference is organized for University of Tsukuba and its partner institutions to discuss and plan the Global Innovation Joint-Degree Program (GIP), which will begin in 2017. Specifi c themes to be discussed at the conference include: the state of progress for GIP, the contents of the double degree schema, prospects for initiating a joint degree, and other presentations regarding the program curriculum and general progress.

Session Organizers: Yoshito Kumagai, Kevin M. McManus Part One Chair: Nobuhiko Akazawa, University of Tsukuba Yoshito Kumagai University of Tsukuba 10:30-10:45 Introduction of GIP Part Two Chair: Nobuhiko Akazawa, University of Tsukuba Toshihiro Kameda University of Tsukuba 10:45-11:00 Space Technologies Helmut Yabar University of Tsukuba 11:00-11:15 Sustainable Environment Studies Caroline F. Benton University of Tsukuba 11:15-11:35 Relationship with Business Partners Part Three Chair: Nobuhiko Akazawa, University of Tsukuba Hsinyu Lee, Ming-Ju Chen National Taiwan University 11:45-12:05 From National Taiwan University Emmanuel Frouté University of Bordeaux 12:05-12:15 From University of Bordeaux TBA University of California, Irvine 12:15-12:25 From University of California, Irvine Part Four Chair: Nobuhiko Akazawa, University of Tsukuba

12:25-13:00 Free Discussion

355 NOTE

356 33 TTB Joint Workshop: Collaborations Beyond Regions and Disciplines

Wednesday, September 30 Venue: Conference Room 405

TTB Joint Workshop: Collaborations Beyond Regions and Disciplines

This session on Japanese studies is jointly organized by the Taiwan Offi ce, Tunis Offi ce, and Bordeaux Offi ce of the University Tsukuba. It is designed to promote research collaborations between scholars from Tsukuba and those from important partner institutions in East Asia, North Africa, and Europe. Participants and iscussants approach topics related to Japan from multidisciplinary and multicultural perspectives. Topics include judo as business, disaster management in comparative perspective, and the Japanese fi nancial crisis from a multicultural point of view. In effect, this session encourages intellectual collaborations beyond traditional boundaries. This session is part of the series that will be jointly organized later this academic year in Taipei (on Taiwanese studies) and Bordeaux (on Mediterranean studies).

Session Organizer: Joji Kijima Discussants: Yutaka Tsujinaka, Hidenao Takahashi, and Remy Magnier-Watanabe

Chair: Joji Kijima, University of Tsukuba 9:00-9:10 Opening Remarks Ssu-Ming Chang National Taipei University 9:10-9:55 Collaborative governance of governments and nonprofi t organizations in catastrophic disaster events Brahim Guizani Tunis Business School, University of Tunis 10:05-10:50 Public capital, deposit insurance and risk-shifting incentives: Evidence from the regulatory responses to the fi nancial crisis in Japan Michel Brousse University of Bordeaux 11:00-11:45 The economics of French judo

11:45-12:00 Wrap-up

357 33-1

Collaborative governance of governments and nonprofi t organizations in catastrophic disaster events

Ssu-Ming Chang1 and Wei-Ning Wu2

1Offi ce of International Affairs, National Taipei University 2Institute of Public Affairs, National Sun Yat-sen University

Disasters lead to high uncertainty and simultaneous demands for resources, which would generate high risks and create high costs to the participants. Over the last decades, the frequency and scales of natural catastrophic events have signifi cantly escalated and caused challenges to better collaboration at regional levels. Scholars and professional organizations have strongly urged the importance of disaster governance. Collaborative governance in catastrophic disaster events has been viewed as a key emergency management mechanism to governments because it creates the expectation that disaster responders will maximize the effective operation of available capability and resource. Hence, it is urgent to develop collaborative governance in catastrophic disaster events. However, current research is still unclear in terms of the role and functions of governments and nonprofi t organizations in collaborative disaster governance. In addition, there are two interesting questions that public managers and network stakeholders would like to know: 1) what are the factors driving collaborative governance of governments and nonprofi t organizations in catastrophic disaster events? 2) how can we strengthen collaborative governance in catastrophic disaster events at the regional levels? Learning from the cases which experience catastrophic disaster events is useful for promoting effective emergency management and developing collaborative mechanisms for unforeseen and foreseen disaster events. In order to understand more about collaborative governance in catastrophic disaster events, this study employs a comparative approach that focuses on both Kaohsiung City (高雄市), Taiwan and Kumamoto Prefecture (熊本縣), Japan. These two local governments suffered severe fl ood issues: Kaohsiung City experienced fl ooding disasters during Typhoon Morakot in 2011; Kumamoto Prefecture was struck by devastating fl oods in 2012. To respond to such catastrophic disaster events, these two cities developed various types of collaborative governance among governments, nonprofi t organizations and other actors in catastrophic disaster events. Through the comparison study of these two cases, we seek to know more about what impedes collaborative governance of governments and nonprofi t organizations in catastrophic disaster events as well as the factors driving collaborative governance mechanisms. Our purpose is to offer better collaborative strategies for handling future catastrophic disaster events at the regional levels.

358 33-2

Public capital, deposit insurance and risk-shifting incentives: Evidence from the regulatory responses to the fi nancial crisis in Japan

Brahim Guizani1 and Wako Watanabe2

1Tunis Business School, Université de Tunis 2Faculty of Business and Commerce, Keio University

Deposit insurance systems are designed to protect a country’s fi nancial system during times of crises by relieving depositors who might otherwise panic and run to their viable banks to withdraw their deposits. There is, however, a broad consensus among economists that the negative side effect of the publicly run deposit insurance is a danger of the moral hazard problem that is insured banks’ excessive risk taking. Indeed, banks that pay a fi xed risk-insensitive premium tend to shift their excessive risk to the deposit insurance agency. However, the incentives for risk-taking can be restrained by a well-functioning regulatory policy that can discipline banks. In this paper we extend the literature by examining the impacts of the temporary blanket deposit insurance, the subsequent regulatory framework and the two rounds of capital injections on Japanese banks’ incentives to shift their risk to the public deposit insurer. Japan is a desirable testing ground for the moral hazard hypothesis because the insurance premium has been perfectly fl at. Using option pricing based models, we compute the actuarially fair deposit insurance premium and the market value of assets and asset volatility for Japanese banks as implied by their stock prices. The fi ndings based on these variables suggest that banks shift risks to the deposit insurer who charges them risk insensitive premiums and that regardless of the insurance coverage policy. The blanket deposit insurance has accelerated banks’ risk-shifting. Well-designed regulatory policies in response to the crisis, however, could effectively restrain banks’ risk-shifting. Not only did the introduction of the prompt corrective action discipline insured banks, but large-scale public capital infusions successfully deleveraged banks whose assets are risky. This effectively mitigated banks’ risk-shifting. Our fi ndings are very strong since several robustness tests could confi rm them.

359 33-3

The economics of French judo

Michel Brousse

University of Bordeaux

France has 60 million inhabitants. The French Judo Federation (FFJ) gathers roughly 600, 000 members within 5, 600 clubs. To this unique mass phenomenon must be added judo performances: 11 Olympic champions and more than 40 World champions. The factors contributing to such a success are varied. The originality of the historic development of judo in France and a specifi c state policy provide some of the answers. From an historical viewpoint, judo in France presents three major characteristics: the fascination the French have for Japan and its culture, the specifi city of the French educational system in its management of sport and leisure activities, and the economic consequences of the early creation of a new job: judo teacher. This was contrary to the Japanese martial arts tradition that generally stayed clear of commercial issues. The system organizing French judo is based on one of the tenets of Jigoro Kano’s phi- losophy - mutual help for mutual benefi ts. It led to the creation of a mutual fund of resources managed by the French Judo Federation under the supervision of its members and of the State. From an organizational standpoint each member of a judo club has to pay a yearly membership to the FFJ. The fee remains the same notwithstanding the age or the level of the participant. The funds collected for the benefi t of all are used to organize federal events. Access to judo matches, camps for athletes, teachers or judo leaders, rank promotions are free of charge. This principle of a mutual fund of resources is paired with the actions of a large number of voluntary helpers. After a brief survey of the context this presentation offers to describe and analyze the con- crete elements of the economics of French judo as well as the politics of the FFJ in the fi elds of development, marketing and mass communication.

360

TGSW2015

Student presentations – Poster Session –

Additional Abstracts (P-1~P-8, P-40~P-41)

P-1 Identifying urinary metabolic changes with vanadium and polycyclic aromatic hydrocarbons exposures using mass-spectrometry-based metabolomics

Chi-Hsin Chen and Chang-Chuan Chan

Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University

Purpose: This study aims to investigate urinary metabolic changes after exposure to petrochemical complex pollutants, vanadium (V) and polycyclic aromatic hydrocarbons (PAHs). Methods: We recruited high exposure groups, who live near a petrochemical complex with higher urinary levels of V and 1-hydroxypyrene (1-OHP; PAHs biomarker), aged 9-15 (n=39) and >55 years n=68). Low exposure groups lived further away from the complex with lower urinary levels of V and 1-OHP, matched to high exposure groups by age 9-15 (n=66) and >55years (n=68). Urine metabolomes were analyzed following Nature protocol using 2 dimensional gas chromatography coupled with time-of-flight mass spectrometry (GCxGC-TOFMS). 3 online databases were used for characterization: Chemical Entities of Biological Interest (ChEBI), Kyoto Encyclopedia of Genes and Genomes (KEGG) and the Human Metabolome Database (HMDB). Partial least-squares-discriminant analysis (PLS-DA) and Student’s t test were used to find metabolic changes between exposure groups. Results: GCxGC-TOFMS extracted 478 peaks. PLS-DA examined metabolic profile variances and found clear separation between exposure groups. On the basis of the variable importance in the projection threshold (VIP>1) and p<0.05 in Student’s t test, as well as identification by ChEBI, KEGG and HMDB databases, 66 and 80 metabolites, were found to cause the separation between high and low exposure groups, in the children and elderly age group, respectively. KEGG characterized these metabolites to be involved mostly in amino acid metabolism, and other energy-related mechanisms including TCA cycle. Conclusion: The metabolites identified can serve as potential indicators for V and PAHs exposures, or intermediate biomarkers associating exposure and possible health outcomes. Characterization of the identified metabolites suggest early effects of V and PAHs include energy-related pathways. These results may provide directions for future health studies.

1 P-2 Electrochemical Genosensors Based on Toehold-mediated Strand Displacement Reaction-triggered Signal Amplification Cascade for Single Nucleotide Polymorphism Genotyping

Amily Fang-ju Jou, Wei-Ching Liao, and Ja-an Annie Ho

Department of Biochemical Science and Technology, College of Life Science, National Taiwan University

A toehold-integrated strand displacement reaction-triggered signal amplification cascade strategy was employed herein to engineer a versatile electrochemical operation for the detection of a single-nucleotide polymorphism (SNP) as a powerful Alzheimer’s disease screening. In addition to the incorporation of a toehold domain in a pre-hybridized DNA duplex, the approach is utilized an additional modification of a displacing strand, the trigger. This trigger, extended with an additional overhang of a few more nucleotides in a staggered position relative to the toehold domain, was used to kinetically control the displacement reaction and initiate a primary nicking enzyme amplification reaction. The generation of amplicon, as a result of the primary amplification reaction, thereby activating an

electrochemical response where a horseradish peroxidase (HRP)/TMB/H2O2 system or liposomal Ru(Hex) tags served as the signal output of a secondary signal amplification. We substantiated the autonomous operation of the strategy and successfully highlighted the application in the determination of a single nucleotide change as an indicator of Alzheimer’s risk.

2 P-3 Investigate on the involvement of DNA topoisomerases in immunoglobulin class switch recombination

Han-Siou Jian, Wan-Ning Leu, Tsai-Kun Li

Department and Graduate Institute of Microbiology, College of Medicine;Center for Biotechnology, National Taiwan University

During transcription, unwinding of the DNA double helix and tracking process lead to positive and negative supercoil arising in front and behind of the advancing RNA polymerase. Nascent RNA strand invades into the DNA duplex and hybridize with the complementary template strand occasionally and creating transient three-stranded structure called R-loop. R-loop is sensitive to chemical agents leading to higher mutagenesis and is believed to link to transcription-associated mutation (TAM) and recombination (TAR), such as somatic hypermutation (SHM) and class switch recombination (CSR). Our previous studies suggested DNA topoisomerases, through resolving DNA topological problems during transcription, can regulate the formation of R-loop. Our aim is to dissect the potential role of topoisomerases in the process of CSR by regulating the formation of R-loop structure. Here, splenic B cells were first isolated from WT mice and screened for candidate topoisomerases by monitoring protein expression in a time course after treatment of switching cytokines, interleuckine-4 (IL-4) and lipopolysaccharide (LPS). The Top1 and Top2β protein expression were up-regulated during CSR, especially at 24 hours after stimulation. We then obtained a CH12F3 cell line from Dr. Honjo lab (Kyoto univ.), which can undergo class switching from surface-IgM to surface-IgA in a much higher frequency after stimulation of interleukine-4 (IL-4), tumor growth factor-β (TGF-β) and CD40 ligand. Interestingly, the protein level changes in topoisomerases in CH12F3 cells after cytokine stimulation are similar to splenic B cells. To further enhance the CSR frequency, CH12F3 with a SCI reporter plasmid (named HTT112 cell line), which has additional switch regions and GFP fluorescent as selection marker, was used. Then we detect the CSR frequency of CH12F3 and HTT112. The CSR frequency is three-time higher than CH12F3 without SCI plasmid, and we thus used HTT112 to carry out our following experiments. To establish a tool for studying the importance of topoisomerases, lentiviruses with shRNA-mediated knockdown of different topoisomerase were generated. After Top1 knockdown in HTT112 cells stimulated to undergo CSR, the surface-IgA amount of cells was measured by flow cytometry. The CSR frequency of Top1 knockdown cells is significantly lower than control ones, suggesting that Top1 might play an important role in the process of CSR. In addition, Top2β expression was successfully knocked down in HTT112 cells, and seems no significant effect on CSR. Detailed underlying mechanism(s) are currently under investigated. In this regard, we directly detected the level of R-loop formation in Top1-knockdown HTT112 cells. Taken together, we have established an in vitro cell-based system to study the topoisomerase-regulated R-loop formation and antibody diversification.

3 P-4 Effects of pesticide residues on natural enemies (Mallada basalis and Eocanthecona furcellata) in strawberry garden

Hao-Ping Wang and Jui-Hung Yen

Master Program for Plant Medicine, National Taiwan University

The generalist predators Mallada basalis and Eocanthecona furcellata are important natural enemies in agricultural ecosystem in Taiwan. The green lacewing M. basalis is considered as an important natural enemy of several pests of economic importance because of their polyphagous feeding habits. The stink bug, E. furcellata, is a predatory insect that can be commonly found on horticultural plants preying on various lepidopterous insect pests in Taiwan. Releases of these predator are carried out, and it is included in the Integrated Pest Management (IPM) programs of several crops. The accurate assessment of the compatibility of various pesticides with predator activity is the key to the success of this strategy. In order to identify products with low toxicity or short duration effects on biological control agents, we assessed contact toxicity, irritancy and residual toxicity of 15 pesticides on M. basalis larvae and contact toxicity, feeding toxicity and residual toxicity on E. furcellata nymphs both under laboratory conditions and semi-field experiments. Pesticides commonly used in either conventional or organic farming in strawberry pest management were selected for the study, including three synthetic fungicides, three synthetic insecticides, one acaricide and eight organic certified pesticides. In semi-field experiments, residues were aged under greenhouse conditions for 0, 1, 2, 3, 5, 7, or 14 d and introducing insects to test residual toxicity. The percentage of mortality was classified according to the IOBC (International Organization for Biological Control) toxicity categories and modified. The results showed that the pesticides greatly differed in their toxicity, in terms of lethal effects, as well as in their persistence. For M. basalis, chlorfluazuron and lamda-cyhalothrin caused high mortality and persistence, and chlorfluazuron was classified as harmful (rating class 2) up to 14 d after the treatment and lamda-cyhalothrin was classified as harmful (rating class 2) up to 2 d after the treatment . In particular, mineral oil was classified as rating class 4, but in semi-field it was low toxic to lacewing larvae. The irritant and repellent effects of low toxic pesticides were also examined on larvae of the lacewings, and there was no statistically significant avoidance between pesticide treatments and water control. It is concluded that these pesticides are not intrinsically irritating or repellent to M. basalis larvae. For E. furcellata, chlorfluazuron caused both high feeding toxicity (rating class 4) and high contact toxicity. In semi-field experiment, chlorfluazuron was low toxic (rating class 2) until 1 d after the treatment, and lamda-cyhalothrin also caused high mortality and persistence, and it was low harmful up to 14 d after the treatment. Imidacloprid consistently caused low toxicity (rating class 2), even after aging for 3 d. Almost all organic certified pesticides and fungicides had low toxicity, and along with the organic certified products and fungicides could be compatible with biological control in strawberry pest management program. This study provides information to guide strawberry growers in their selection of pesticides, and appropriately releasing time of M. basalis larvae and E. furcellata nymphs after pesticides application.

Key words: Biological control, Strawberry, Mallada basalis, Eocanthecona furcellata.

4 P-5 The role of TopB and RecQ in the regulation of R-loop formation

Hsiao-Han Chiu, Yi-Chun Chen, Tsai-Kun Li

Department and Graduate Institute of Microbiology, College of Medicine;Center for Biotechnology, National Taiwan University

During RNA transcription, the topology of DNA structure changes. Notably, loosely negative supercoiling formed behind RNA polymerase might allow the nascent RNA inserting into the negative supercoiled DNA helix and pairing with template DNA to form the RNA-DNA hybrid leading the formation of an abnormal R-loop structure consisting of RNA-DNA hybrid and single-strand DNA (ssDNA). The exposed ssDNA could be one potential targeting substrate of activation-induced cytidine deaminase (AID), which is activated in B cells and eventually leading to antibody diversification. AID acts on cytosine causing deamination and turning it into uracil. Through different repair and recombination pathways, C  U conversions further result into somatic hypermutation (SHM) and class switch recombination (CSR). In addition, the ssDNA region is also very unstable and prone to form secondary structures or DNA breaks. Further, excessively accumulated R-loops impede the elongation of helical tracking enzymes on DNA to block transcription, replication and other DNA metabolism processes. For the reasons above, understanding of factors involved in the regulation of R-loop formation is important. Our lab’s previous results suggested that bacterial DNA topoisomerases, TopA and Gyrase, are regulatory factors of R-loop formation. Bacterial topoisomerase III (TopB) also relaxes negatively supercoiled DNA and RecQ helicase resolves secondary structures generated during transcription or replication processes. Moreover, TopB and RecQ could also act together to maintain genome integrity. Here, we used Escherichia coli as a model system and employed following assays to study the contributing factors. Specifically, S9.6 antibodies were used to detect the RNA-DNA hybrid in R-loop structure. Moreover, AID-induced mutagenesis (ASM) assay with fluctuation test is also established by ectopically expressed AID into the wild-type and different mutant strains to obtain the ASM folds that indirectly represents the amount of R-loops. We observed that the signal intensity of S9.6 immuno-staining (i.e. the level of RNA-DNA hybrid) was elevated in the ΔtopB, ΔtopB ΔrecQ, but not ΔrecQ deleted cells. The level of S9.6 signaling was reduced only after RNase H treatment suggesting that S9.6 signaling represents R-loop and TopB can negatively regulate the formation of R-loop. Interestingly, spontaneous mutation frequency of ΔtopB ΔrecQ double mutant is two-fold higher than the wild-type strain but the ASM fold is decreased, possibly due to that the defects of double mutant cannot tolerate additional AID-stimulated mutagenesis and leading to bacterial cell death. In addition, DNA damage activates the SOS response that subsequently leads to increased expression of repair and other factors and arrest of cell division (i.e. formation of filamentous cells). The percentage of abnormal filamentous cells increased in the ΔtopB mutant. These results are in agreement with the above observation and notion that the higher R-loop level in the ΔtopB mutant may lead to DNA damage and cellular filamentous phenotype. Taken together, TopB functions in inhibition of R-loop formation and plays an important role in genome stability.

5 P-6 To Adjust Heading Time of Broccoli by Marker Assisted Selection

Jou-yi Lee1, Cian-he Shen2, Chieh-ying Lee2, Kae-kang Hwu1, Yann-rong Lin1

1Department of Agronomy, National Taiwan University 2Known-You Seed Co., Ltd, Kaohsiung, Taiwan

Broccoli (Brassica oleracea L. var italica) has been considered a valuable vegetable for its anti-cancer properties. Since Broccoli originated in the northern and western coasts of the Mediterranean, the European temperate regions, it prefers growing in cool temperature. High temperature in summer is unfavorable for broccoli to bolt, resulting irregular shape and uneven size of heads consequently. In Taiwan, Broccoli only can be cultivated from September to the following April. Therefore, great demands of broccoli have to be relied on massive imports in summer. To breed new broccoli cultivars with early heading date to meet market requirement is the final goal. We identified the genes or quantitative trait loci (QTLs) conferring heading date first and then applied the result to brocolli breeding program by

marker-assisted selection. The 192 F2 individuals of BLM98-29 with early heading time  BLM98-25 with late heading time were genotyped with 126 simple sequence repeat (SSR) markers and recorded heading time and head shape. After linkage analysis and interval mapping, two major QTLs, mapped on chromosomes 3 and 6, could explain 44.05% of phenotypic variance. The flanking markers of these two QTLs were used as foreground selection to introgress heading date genes, and the other polymorphic SSRs distritbuted 9 chromsomes were used as background selection to recover the genome of the elite cultivar.

Three individuals selected from 188 F2 by MAS were served as the male parents to backcross to elite brocolli, BLM98-25. At the consequenty three generations of backcross which were applied foreground and backgroud selection with markers, 12 individuals selected from 128

BC3F1 contain more than 91% of BLM98-25 genome and show the early heading

characteristic. Until now, four selected BC3F1 individuals were selfed to establish BC3F2, and one more round of MAS will be executed to have accesssions with early heading date and good horticultual traits. New early-heading broccoli cultivars are expected to release in markets in near future, which can be promoted in the domestic and southern Asian counties. Furthermore, the optimized strategy of broccoli breeding by MAs will faciliate crop seed enterprise in Taiwan.

6 P-7 The Roles of LPA Receptors During Erythropoiesis/Megakaryopoiesis in mice

Jui-Chung Chiang, Hsinyu Lee

Department of Life science, National Taiwan University

Hematopoiesis is a differential process to form blood cellular components during embryonic development and adulthood in blood system. In myeloid differentiation of definitive(adult-type) hematopoiesis, erythroid and megakaryocytic lineages arise from common progenitor, megakaryocyte-erythroid progenitor (MEP). Previous studies showed the

expression level of LPA receptors are up-regulated on Common Myeloid Progenitors (CMP). It indicated LPA and LPA receptors axis pathway might be involved in myeloid differentiation. Lysophosphatidic acid (LPA) is an extracellular lysophospholipid which regulates multiple biological functions through activating different G-protein-coupled receptor, LPA receptor 1-6. In our previous research, LPA was demonstrated to play as a mediator for erythropoiesis + /megakaryopoiesis through LPA2 and LPA3 in CD34 human hematopoiesis stem cells (hHSC) and zebrafish model. In this study, we used the pharmacological chemicals to further

investigate the roles of LPA and its receptor LPA2 and LPA 3 during definitive erythropoiesis/

megakaryopoiesis in mice. LPA2 receptor agonist GRI977143 and LPA3 agonist 1-oleoyl-2-O-methyl-rac-glycerophosphothionate (OMPT) were applied to BALB/c mice. Then blood sample was collected and analyzed with Complete Blood Count (CBC) to identify the composition changing of erythrocyte and platelet. Furthermore, flow cytometry and immunohistochemistry were performed to identify differentiation-stage-specific erythroid progenitors and megakaryocyte from spleen and bone marrow samples. Our results demonstrated that the two agonists both reduced the megakaryocyte differentiation and

amount of platelets. On the other hand, LPA2 agonist inhibited erythropoiesis, whereas LPA3

agonists promoted this process. We concluded that LPA 2 and LPA3 both down-regulated the production of platelet, but these two receptors have opposite functions on erythropoiesis. However, the mechanisms in charge for the regulation of erythropoiesis/megakaryopoiesis

through LPA2 and LPA3 remain unclear and further investigations are needed to make contribution to medical applications.

7 P-8 The putative roles of matrix metalloproteinases during anterior regeneration in Aeolosoma viride

Tzu-Lun Tseng and Jiun-Hong Chen

Department of Life Science, National Taiwan University

Matrix metalloproteinases (MMPs) play key roles in turnover of extracellular matrix (ECM) and serve as important regulators of cell-ECM interaction during development and regeneration. In previous studies, MMP-2, MMP-9 and MMP-14 are found involved in regenerative processes in vertebrates. However, in invertebrates, no MMP-2 or MMP-9 has been found. So, the function of MMPs in the regenerative ability of invertebrates is an interesting question. In this research, a fresh water annelid, Aeolosoma viride, with high regenerative ability, was used to solve out this question. In the NGS transcriptome data of A. viride, only the partial sequences of MMP-14, MMP-17, MMP-19 and MMP-21 can be found. GM6001, a MMPs inhibitor, had been treated during regeneration in A. viride and found that inhibiting MMPs activities at the early stage of anterior regeneration could delay the whole regenerative process, which means MMPs play some roles at the early stage of regeneration. mmp-14, mmp-17, mmp-19 and mmp-21 sequences had been cloned, and, in phylogenetic tree, they group with MMPs of other species. The qPCR data of blastema at different regenerative time point showed that mmp-21 and mmp-17 expressed highly at the early stage of anterior regeneration, but mmp-14 and mmp-19 showed no differences in expression during regeneration. In situ hybridization analysis also indicated that high expression of mmp-21 in blastema at 12, 24 and 48 hours post amputation (hpa). These data suggested that the MMP-21 might be a regulator at early stage of regeneration. On the other hand, SDS-PAGE gelatin zymography showed the highest protease activity at 24 hpa blastema. The data suggested that MMPs have some effects on early stage of anterior regeneration, and MMP-17 and MMP-21 might be the key factors in the processes. The relationship between MMPs and the regulation of MMPs need further research to resolve.

8 P-40 Bio-inspired claw-wheel transformable robotics.

Yu-Hsiang Lin and Jui-Jen Chou

Mechatronics Engineering, Department of Bio-Industrial, National Taiwan University

We have been conducting research into improving wheel-legged transformable robot’s mechanical durability and mission flexibility while adopting simple structure to realize our robot’s transformation on wheels’ morphology. In our design, a circular wheel module comprises of a pair of s-shaped claw attached on two coaxial shafts separately, a clutch-differential hybrid module controlled by a small servo motor and a DC motor with optical encoder served as a wheel module’s main kinematic energy source. Furthermore, we have combined 4 wheel modules to form a tetrapod robot and successfully used the robot to simulate the robot’s driving, turning and wheels’ morphology switching on barely flat terrain and stair climbing as well as irregularities crossing under the robot’s claw-wheel mode.

9 P-41 Characterization of the late blight resistant gene qPh2.1 in the wild tomato accession L3708 (Solanum pimpinellifolium L.)

Yu-Ya Liang and Kai-Yi Chen

Department of Agronomy, National Taiwan University

Our previous study discovered a new quantitative trait loci qPh2.1 conferring late blight resistance in the wild tomato accession L3708 (Solanum pimpinellifolium L.), in addition to the known Ph-3 resistant gene. qPh2.1 was genetically mapped at the proximal end of the tomato short arm chromosome 2, by inoculation of a highly aggressive isolate Pi733 that defeated the late blight resistance of three differential hosts, TS33, WVa700, and LA1033 which confers resistant gene Ph-1, Ph-2, and Ph-5t, respectively. In the current study, we validated the resistance of qPh2.1 using isogenic lines derived from the progenies of L3708. Experimental data suggested that the resistant allele of qPh2.1 was recessive and was as strong as the Ph-3 resistance against the isolate Pi733a. Also, the qPh2.1 gene was delimited in the annotated chromosomal region between 8Mb and 35Mb on chromosome 2 of the tomato SL2.5 genomic sequences.

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