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4 Dear Colleagues and Friends

It is my great pleasure to welcome guests from all over the world to the 5th Annual Tsukuba Global Science Week (TGSW2014). Last year, a variety of study fields including not only natural and social sciences, but Arts and sports sciences, participated in the TGSW2013 to celebrate the 40th + 101st anniversary of University of Tsukuba. This year, all of our ten faculties participate in the TGSW2014 as an official university-wide event to tighten international networks and to enhance interdisciplinary collaborations. University of Tsukuba was established in 1973, evolving from our predecessor, the University of Education, whose establishment dates back to 1872. During 41 years of the history of University of Tsukuba, we have produced not only multiple Nobel Laureates but also 61 medals in Olympic games. Ultimate achievements in both academic and sport activities stem from a legacy of our founding president, Jigoro Kano, the father of Judo, who highly valued the combination of sound ‘body and mind.’ To advance this tradition and to evolve further in innovative research and education, we decided to create a new and unique program, “Campus-in-Campus.” Bilateral top-level agreements between our partner universities and us enable our students to attend classes in our partner universities and vice versa. Students and researchers at each university can travel to and work at a partner university under the supervision of a partner professor most efficiently. This new program will surely strengthen the bond among partner universities. Today, the human beings face numerous global issues such as food crisis, energy issues, environmental risks, never-ending wars, and poverty. To address these critical issues, we need to collaborate internationally as well as in an interdisciplinary manner, by bringing together the fields of public health, medical science, biological science, sports science, food science, information science, politics, economics, humanities, arts, and more. TGSW2014 is an excellent opportunity for international and interdisciplinary discussion, sharing cutting- edge research and creative activities. Lastly, I would like to thank all of you for your participation and sincerely hope that you will enjoy this invaluable three-day event. I look forward to meeting with each of you during the week to tighten our friendship.

Kyosuke Nagata President University of Tsukuba

5 Dear All Participants,

I would like to extend my warmest welcome to all delegates attending Tsukuba Global Science Week (TGSW) 2014. The University of Tsukuba will celebrate its 41th anniversary this week. We continue to spearhead internationalization of Japanese higher education and bridge different research areas. It would be my distinct pleasure if TGSW2014 can provide an opportunity for all participants to expand their research activities and strengthen their international networks. Interdisciplinary research is known to be one of the powerful approaches towards new discoveries. It propels us to fearlessly confront challenges against the global issues such as aging of population, energy shortage and environmental destruction. TGSW2014 covers a wide range of fields including public health, medical science, sports science, food science, information science, politics and economics, humanities, arts, and more. Each participant is very welcome to join the sessions of totally different fields. I believe that such mixture of participants provides the opportunity to learn from different perspectives. This year, we expect students, researchers, professors, and administrators coming from all over the world. Guests come from Bahrain, Brazil, Canada, Chile, China, France, Germany, Greek, Hungary, India, Indonesia, Jordan, Morocco, Myanmar, Nepal, Netherlands, Russia, South Korea, Taiwan, Thailand, Tunisia, United Kingdom, United States, Viet Nam, and of course . With our university slogan, “Imagine the Future.”, in mind, we would like to discuss the concrete steps toward resolving global issues and creating a better world for all. I would like to thank all of you for coming and hope that you will enjoy the conference. I hope you will find a hint for improving the world in this forum where people from different academic fields, and backgrounds have come together to discuss cutting-edge ideas.

Yasuo Miake Vice President University of Tsukuba

6 Opening Session

Global Initiatives in Higher Education and Research

7 Sep 28 (Sun) Hall

Opening Session: Global Initiatives in Higher Education and Research

9:00-9:05 Yasuo Miake University of Tsukuba Opening Remark

University of Tsukuba: 9:05-9:20 Kyosuke Nagata University of Tsukuba A Bold Action Plan for the Next Decade on a Tradition of Innovation

9:20-9:40 Pan-Chyr Yang National Taiwan University Translational Research and Precision Cancer Therapy in Taiwan

9:40-10:00 Vincent Dousset University of Bordeaux The 2014 Launch of the University of Bordeaux

10:00-10:20 Jacob E. Levin University of California, Irvine Leveraging Global Partnerships in the Face of an Uncertain Future

Formerly Nissan Professor of The Progress of Japanese Studies with Particular Reference to the UK 10:20-10:40 Arthur (J. A. A.) Stockwin Modern Japanese Studies, and Australia University of Oxford

8

3 / 26 ページ Sep 28 (Sun) Hall

Opening Session: Global Initiatives in Higher Education and Research

9:00-9:05 Yasuo Miake University of Tsukuba Opening Remark

University of Tsukuba: 9:05-9:20 Kyosuke Nagata University of Tsukuba A Bold Action Plan for the Next Decade on a Tradition of Innovation

9:20-9:40 Pan-Chyr Yang National Taiwan University Translational Research and Precision Cancer Therapy in Taiwan

9:40-10:00 Vincent Dousset University of Bordeaux The 2014 Launch of the University of Bordeaux

10:00-10:20 Jacob E. Levin University of California, Irvine Leveraging Global Partnerships in the Face of an Uncertain Future

Formerly Nissan Professor of The Progress of Japanese Studies with Particular Reference to the UK 10:20-10:40 Arthur (J. A. A.) Stockwin Modern Japanese Studies, and Australia University of Oxford

9

3 / 26 ページ University of Tsukuba: A Bold Action Plan for the Next Decade on a Tradition of Innovation

Kyosuke Nagata

President, University of Tsukuba

The University of Tsukuba has a 40 year history of innovation. All major domestic league tables point to the fact that we are one of the top research-oriented universities in Japan. We count among our graduates and faculty members three Nobel Laureates, seventy Olympic medalists, countless educators, researchers, athletes and artists who have helped make Japan what it is today. As you can see, we have a vast and beautifully conceived campus not found anywhere else in Japan. We occupy a strategically advantageous position in the heart of Tsukuba Science City, which hosts over 300 research institutions with researchers from all over the world engaged in cutting edge research. Thus, we have a number of unique features that can be used to good effect to successfully collaborate with world-class universities. How can we contribute to building a next generation earth? To fully explore our potential in the global arena, we shall invest substantial human and financial resources over the next decade in international exchange and collaboration. A range of new ideas are now being materialized. The most exciting of all is what we call the CAMPUS-in-CAMPUS project – an ambitious project whereby we seek to create a series of miniature off-shore campuses in our partner institutions, and to invite our overseas partners to establish their miniature off-shore campuses in Tsukuba. Once the CAMPUS-in-CAMPUS scheme is in place, our and your students, together with students of our closest allies, will be able to study together physically as well as on-line. You, students, can find and take classes held in not only your campus but also in the campuses of your partners. This is also the case for researchers and university staff members. You, researchers, may carry out experiments in your partner campuses. All these schemes cannot be done without the help of our partner institutions. TGSW is a good chance not only as a great showcase of our individual and collective scientific achievements, but also for incubation of our ties with partner institutions in and outside Japan.

10 Translational Research and Precision Cancer Therapy in Taiwan

Pan-Chyr Yang MD, PhD

President, National Taiwan University Professor, College of Medicine

Clinical trials are critical for translating scientific discoveries from the laboratory into useful products for the prevention, diagnosis and treatment of human diseases. The National Science Council funded the National Research Program for Biopharmaceuticals (NRPB) since 2011 to promote the translational and clinical research in Taiwan, including the establishment of Taiwan national bio-specimen banks and clinical trial consortiums. The NRPB disease- specific national bio-specimen banks facilitate multi-center, high quality, bio-specimen deposit and retrieval, with patients’ complete clinical and epidemiological data and bio-informatics to promote translational research. The NRPB Taiwan Clinical Trial Consortiums consist of lung cancer, liver cancer/diseases, Helicobacter pylori and GI malignencies, oncology phase - I consortium, breast cancer, gynecological cancers, chronic obstructive pulmonary disease, hypertension, lipid and atherosclerosis, pediatric infectious diseases and mental disorder consortiums. We established central IRB to facilitate the review process are participating in many global new drug clinical trials of major international pharmaceutical companies as their preferred partners. We also take leadership in international clinical trials as chairmen or advisory board members of the studies for the sponsors or to perform first-in-human phase - I new drug clinical trials. NRPB is building up the translational research and clinical infrastructures in Taiwan and establish Taiwan as a center of excellence for clinical research and clinical trial in Asia-Pacific. To implement the precision therapy for cancer patients, we have established a national reference laboratory to provide high quality and standardized gene testing for all lung cancer patients. The clinicians could treat the patients based on the genetic alterations to select the most effective therapy; including the EGFR (50%, response to Gefitnib, Erlotinib, Afatinib), EML4-ALK (3-5%, Crizotinib), KRAS (5%, Sorafenib, chemotherapy), MET (3-5%, ARQ- 197, others), BRAF(3%, Sorafenib, others), ERBB2 (3%, Afatinib or Trastuzumab), etc.. Our National Health Insurance reimbursed the Gefitnib and Erlotinib as first line therapy for EGFR mutant lung cancer patients since 2011. The Genetic Epidemiology of Lung Cancer in Taiwan (GELAC) collaborated with NIH and identified 5 specific susceptibility lociTERT ( , TP63, HLA Classs II, POS1-DCBLD1 and VTI1A) in never-smoking women in Asia. The risk genetic loci may be useful to identify high-risk group of patients who can benefit from low dose CT for early detection of lung cancer. We also develop new strategy to overcome drug resistance and targeting cancer stem cells. With the implementation of nation-wide gene testing and precision therapy, the overall 5-year survival for NSCLC has been improved from 15.8% to 31.6% from 2009 to 2013.

11 The 2014 Launch of the University of Bordeaux

Vincent Dousset

Vice-President, University of Bordeaux – International Affairs Professor of Medical Imaging, University of Bordeaux & University Hospital of Bordeaux

Following national reforms and incentives for creating ten major international universities in France (2008), several universities of Bordeaux has decided to merge and to launch in 2014 the University of Bordeaux. Historically, the first University of Bordeaux has been created in 1441 by the bishop Pey Berland. Over time, the University has been divided up in several ones or in independent faculties behind political issues like in 1968 to lower the role of students obstructing the national policies. The fragmentation led to three major drawbacks: 1) a reduction in the capability to create bridges between disciplines, which are recognized as having a positive impact in student education and creativity; 2) a difficulty to manage the research activities at a sufficient scale and to support financially and materially research of high quality; 3) to appear on the international scenery by the quality of diplomas, the excellence of research and in the numerous rankings. The presentation will focus on the steps that brought to the new University of Bordeaux, the new organization chart, the ambitions in education and research, the process of recognition that made the University of Bordeaux laureate of the French national award “initiative of excellence” and the new management of international affairs which is at the heart of its political issues.

12 Leveraging Global Partnerships in the Face of an Uncertain Future

Jacob E. Levin, PhD

Office of Research, University of California, Irvine

The problems that plague modern society and the questions that arouse human curiosity are universal – largely independent of our country of origin or what language we speak. It stands to reason that insight into these fundamental mysteries, and solutions to these complex and challenging problems, will come through the joint efforts of a diverse and global team – of scientists and engineers, physicians and humanists, artists and educators, and with the involvement of universities, government, private organizations and industry. For the largest and most intractable of these problems, people, resources and funding will need to be mobilized from across the world, tools employed from all fields and sectors. Especially in these financially uncertain times, multi-pronged interdisciplinary international partnerships must be forged, strengthened, and managed, using all the capabilities at our disposal, in order to effectively synthesize and leverage our unique individual strengths and capabilities. Broadly representative cross-sector partnerships are being formed to address everything from the greening of college campuses to the development of new drugs and medical therapies to preparing our athletes for the Olympics. Modern technologies and communication tools are aiding the formation of these international collaborations, as is an ever-increasing viewpoint of global engagement, and responsibility for creating a sustainable future, being adopted by Universities, research funding agencies and the government. A few examples of these partnerships will be discussed, in the context of the multi-national multi-disciplinary collaborative environment that is Tsukuba Global Science Week itself.

13 The Progress of Japanese Studies with Particular Reference to the UK and Australia

Arthur (J.A.A.) Stockwin

Formerly Nissan Professor of Japanese Studies and Director, Nissan Institute of Japanese Studies; Emeritus Fellow, St. Antony’s College, University of Oxford Order of the Rising Sun, Gold Rays with Neck Ribbon

Serious study of Japan, and teaching about Japan, scarcely existed at university level in the UK and Australia before the end of the Second World War. One estimate puts the number of Australians fluent in Japanese in the 1930s at seven. There were a few exceptions (a Japanese Studies Fellow at the University of Oxford around 1910, a Japanese Studies Professor at the University of Sydney for some years after the First World War), but it was not until military- run Japanese language courses in the early 1940s produced numbers of fluent Japanese speak- ers that some universities began to regard Japan as a possible area for study. But not until the Japanese ‘economic miracle’ began to attract international attention in the 1960s did Japanese studies really come into its own. This continued into the late 1980s and beyond, with some universities in both the UK and Australia reporting an ‘enrolment tsunami’ in courses re- lating to Japan (including language courses). In Australia in particular, Japanese became a major language taught in schools as well. With the Japanese economy stagnant in the 1990s, what had been over-expansion was corrected by retrenchment, but from the new millennium Japanese studies had become consolidated and achieved both quality and depth. Even though Chinese studies have by some measures overtaken those of Japan, both the UK and Australia contribute extensively to research and teaching on many aspects of Japan, both historical and contemporary, and in an increasing range of disciplines, principally but not exclusively in the humanities and the social sciences.

14 NOTE

15 NOTE

16 Joint Faculty Conference of UT and NTU – Synergy, Alliance and a Better Future II –

Research Administration Office University of Tsukuba & Office of International Affairs National Taiwan University

17 Sep 28 (Sun) Hall

Joint Faculty Conference of UT and NTU ―Synergy, Alliance and a better Future II―

11:00-11:20 Caroline F. Benton University of Tsukuba Transforming Higher Education in an Increasingly Globalized World

11:20-11:40 Bennett Yu-Hsiang Fu National Taiwan University Beyond the Student Exchange: NTU Plus Academy

11:40-12:00 Toshiyuki Inagaki University of Tsukuba Automated Driving: Where Are We Headed?

Locomotion and manipulation: Motion generation from bio-inspired 12:00-12:20 Pei-Chun Lin National Taiwan University engineering aspects

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4 / 26 ページ Sep 28 (Sun) Hall

Joint Faculty Conference of UT and NTU ―Synergy, Alliance and a better Future II―

11:00-11:20 Caroline F. Benton University of Tsukuba Transforming Higher Education in an Increasingly Globalized World

11:20-11:40 Bennett Yu-Hsiang Fu National Taiwan University Beyond the Student Exchange: NTU Plus Academy

11:40-12:00 Toshiyuki Inagaki University of Tsukuba Automated Driving: Where Are We Headed?

Locomotion and manipulation: Motion generation from bio-inspired 12:00-12:20 Pei-Chun Lin National Taiwan University engineering aspects

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4 / 26 ページ Transforming Higher Education in an Increasingly Globalized World

Caroline F. Benton

University of Tsukuba Vice President, Global Affairs

Today’s globalized world is characterized by accelerating levels of complexity, interdependency and change. Twenty, thirty years from now will look nothing like today. New types of jobs will replace current ones and new manners of interaction among people across organizations and national borders will emerge. Issues such as resource scarcity, continued deterioration of the environment, and regional conflict will have even wider ranging consequences with greater global impact, and will require transborder collaboration to resolve. Such a future requires efforts from not only a limited number of global leaders, but also from persons in all areas of society who can work across cultures and have the ability and competency to flexibly navigate a continuously evolving world. As educators of young people and custodians of the present state of academia, it is our responsibility to ensure that our youth are equipped to handle the coming future. To this end, we must rethink not only what we teach and research, but also why and how we do so. With ever-increasing change and complexity, it is not enough to transfer knowledge from a single static field of knowledge or discipline. We must nurture our students to be leaders of change with the competence to look past status quos, to recognize the connections among the various issues and stakeholders of society, and to negotiate across diverse value sets and paradigms. This talk will address the emerging challenges that the future generation will face and the competencies they will need, and how our university will help prepare them through continuous innovation in education, research and university governance. By spearheading reform in higher education, we aim to transform our university into a truly transborder institution.

20 Beyond the Student Exchange: NTU Plus Academy

Dr. Bennett Yu-Hsiang Fu

Associate Dean, Office of International Affairs Professor of English, Department of Foreign Languages and Literatures National Taiwan University

With the promise of diverse academic opportunities, awareness of cultural differences, and personality development, international student mobility has become a popular and important trend amongst higher education institutions. From the development of student exchange programs, many institutions are constantly looking for more dynamic ways to attract international students to their campus. In this talk, National Taiwan University will share the insights into and experiences of spinning or adding on to the standard exchange program to accommodate different student needs. The talk will focus on how NTU expands its international opportunities on campus by developing a series of Summer+ programs, Spring+ programs, and customized programs for partner universities. The University is now moving forward to integrate these successful tailor-made programs in a new concept “NTU Plus Academy” to cater to diverse needs of international students at NTU.

21 Automated Driving: Where Are We Headed?

Toshiyuki Inagaki1,2

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

Today’s machine can sense and analyze a situation, decide what must be done, and implement control actions. Such smart machines can be seen at many places in our society. Aircraft have been highly automated for more than two decades. Although human pilots have to take care of the takeoff phase for several minutes, the rest of the flight phases from the initial climb to the final approach and landing can be dealt with by the computers for around 10 hours in cases of international flights. Now autonomous cars have become part of everyday conversation. People make up their own mental models of the autonomous cars. Some may expect that they would be freed from stressful driving tasks and that they can enjoy using smartphones on their whole way to the destination. Some others may assume that autonomous cars should be accident-free, because human errors can never happen. However, it is not clear what type of automated driving we should implement. Several levels can be distinguished for automated driving: (1) Driver assisted, (2) partial automation, (3) conditional automation, (4) high automation, and (5) full automation. Human driver’s role differs from level to level. For instance, in some of these levels, control authority is traded from automation to the human driver based on the automation’s decision. It is well known that automation sometimes bring negative effects, such as the out-of-the-loop performance problem, loss of situation awareness, complacency or overtrust, automation surprises. Can the human driver cope with the trading of authority appropriately when he or she has not monitored the driving environment? What kind of advantages can the driver have, if we ask him or her to monitor the driving environment all the time? Can automated driving be realized under the Convention of Road Traffic that states that “Every driver of a vehicle shall in all circumstances have his vehicle under control so as to be able to exercise due and proper care and to be at all times in a position to perform all maneuvers required of him”? There are still many issues to be solved technologically as well as legally.

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24 Optimization and Design of Medical Services

Division of Policy and Planning Sciences, Faculty of Engineering, Information and Systems, University of Tsukuba

25 Sep 28 (Sun) International Conference Room

Optimization and Design of Medical Services

Chair Morimitsu Kurino University of Tsukuba

10:45-11:00 Morimitsu Kurino University of Tsukuba Introduction

11:00-11:20 Tayfun Sönmez Boston College Living Donor Lobar Liver/Lung Exchange

11:20-11:40 Takahiro Oto Okayama University Current status of lung transplantation in Japan

Efficiency and Equity Consequences of Live-Donor Organ Exchange 11:40-12:00 Utku Ünver Boston College Policies: The Case for Kidneys and Livers

Liver transplantation for liver cancer in Japan -Differences between 12:00-12:20 Takahito Yagi Okayama University adults and children-

12:20-12:40 Kenji Yuzawa Mito Medical Center Present status of organ transplantation in Japan

Sep 28 (Sun) Multimedia Room

Optimization and Design of Medical Services (Panel Discussion)

14:15-15:45 Panel Discussion

15:45-16:00 Coffee Break

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7 / 26 ページ Sep 28 (Sun) International Conference Room

Optimization and Design of Medical Services

Chair Morimitsu Kurino University of Tsukuba

10:45-11:00 Morimitsu Kurino University of Tsukuba Introduction

11:00-11:20 Tayfun Sönmez Boston College Living Donor Lobar Liver/Lung Exchange

11:20-11:40 Takahiro Oto Okayama University Current status of lung transplantation in Japan

Efficiency and Equity Consequences of Live-Donor Organ Exchange 11:40-12:00 Utku Ünver Boston College Policies: The Case for Kidneys and Livers

Liver transplantation for liver cancer in Japan -Differences between 12:00-12:20 Takahito Yagi Okayama University adults and children-

12:20-12:40 Kenji Yuzawa Mito Medical Center Present status of organ transplantation in Japan

Sep 28 (Sun) Multimedia Room

Optimization and Design of Medical Services (Panel Discussion)

14:15-15:45 Panel Discussion

15:45-16:00 Coffee Break

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7 / 26 ページ Living Donor Lobar Liver/Lung Exchange

Haluk Ergin1, Tayfun Sönmez2 and Utku Ünver3

1Department of Economics, University of California, Berkeley 2Department of Economics, Boston College 3Department of Economics, Boston College

Live donor transplants are carried out both for livers and lungs, where a lobe of these organs from a donor is transplanted to the patient. Since 2010, a handful of live donor liver exchanges have been conducted in South Korea and Hong Kong. In addition to blood-type compatibility, size-compatibility is also essential for a successful transplant for both organs. Furthermore, live donor lung transplanta-tion requires two donors for each patient where each donor donates a lung lobe to the patient. Live donor lung exchange is proposed as a new lung transplan-tation modality. Models of liver exchange and lung exchange are introduced and analyzed. Welfare gains of these organ exchanges will be simulated.

28 Current status of lung transplantation in Japan

Takahiro Oto1

1Department of Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmacological Sciences

To overcome severe donor shortage, maximizing organs transplanted per brain death donor and expanded the donor pool using living donors are mandatory. Successful uses of marginal lungs with ex-vivo lung re-conditioning contribute to increase the number of available lung graft. Utilization of adult living donor middle-lobe can save critically ill small children and infant who otherwise cannot survive size-matched brain-dead donor organs. Overall, the strategies Japan has adopted to overcome donor shortage can provide useful insights on how to increase organ transplantations.

29 Efficiency and Equity Consequences of Live-Donor Organ Exchange Policies: The Case for Kidneys and Livers

Haluk Ergin1, Tayfun Sönmez2, M. Utku Ünver2

1UC Berkeley ,2Boston College

(presented by M. Utku Ünver)

Live-donor kidney exchanges have become commonplace in many countries within the last decade. We give a summary of what has been done, referring to our and others’ earlier work, and what still needs to be addressed for achieving higher gains from kidney exchange from an economic organization point of view. We show that incentivizing compatible pairs to participate in an ethically acceptable manner will help more incompatible pairs in exchange, and can lead to the creation of a single large clearinghouse instead of multiple small ones which will in turn help highly sensitized patients.

Live-donor liver exchange has been a relatively new modality in organ transplantation and some exchanges have been conducted primarily in South Korea. Different from kidneys, it requires strict size compatibility considerations and tissue incompatibility does not play a major role. In this paper we explore the structure of optimal liver-exchanges and show that although the friction caused by size incompatibility decreases direct donations, through utilization of exchanges it caqn increase the total number of transplants.

30 Liver transplantation for liver cancer in Japan - Differences between adults and children -

Takahito Yagi

Hepato-Biliary & Pancreatic Surgery, Okayama University Hospital

Liver transplantation (LT) is the only acceptable therapeutic arm for cancer therapy in solid organ transplantation. In adults, LT is used for relatively early hepatocellular carcinoma (HCC). This criteria of LT for HCC has been named as Milan Criteria by Mazzaferro et al. MC means a single nodule smaller than 5cm in diameter or multiple nodules fewer than three and smaller than 3cm in diameter each. As long as met Milan Criteria, four year survival of LT for HCC was 75%, just same as those of LT for chronic hepatic failure without HCC. LT for HCC occupied 20.5% (1131/5510 cases) in Japanese LT registry 2007 and 24.5% in our institute. But multi-armed intensive pretreatment including hepatectomy, ablation and chemoembolization is able to make over Milan HCCs into met Milan HCCs. Such down staging pretreatment is called “intention to treat”, and will increase met Milan population. In children, histo-pathological subtype of liver cancer is hepatoblastoma (HBT), and quite different from that of adult. Therefore, clinic-pathological nature and LT indication of HBT are not same as adult liver cancer (HCC). Indication of LT for HBT is unresectable advanced tumor in Stage III or IV. Even HBT with distant metastasis, LT is acceptable when metastatic nodule are surgically removed or not viable by intensive chemotherapy. In such advanced HBT, primary LT has better survival than that of rescue LT after in compete hepatectomy. I herein presents these 2 types of LC in Japan and our institute.

31 Present status of organ transplantation in Japan

Kenji Yuzawa

Director, Department of Transplantation Surgery, National Hospital Organization Mito Medical Center Chair, Case Registration Committee, The Japan Society for Transplantation

Japan is a developed country in many medical field. But, only in organ transplantation, Japan is a developing country. Many Japanese transplant surgeons had training in the United States and Europe. Many basic science articles on transplantation were described by Japanese. More than 80% recipients after organ transplantation had the immunosuppressive drug developed in Tsukuba, Japan. Japan has a leadership in organ transplantation in the world. After the organ transplantation law was established in 1997, the number of brain death donors was limited, because the written consent of the donor was necessary. So many patients who needed organ transplantation went abroad. In 2008, the Declaration of Istanbul by the international transplantation society and WHO stated organs for transplantation should be equitably allocated within own countries. Many Japanese patients became unable to go abroad for organ transplantation. In 2009, the law was revised, and the written consent was unnecessary. But the numbers of deceased donors were remained about 110 per year. Surprisingly, in 2013, the number of deceased donor was decreased to 84. In these circumstances, in Japan, the special fields in living organ transplantation were developed. These are ABO blood group incompatible organ transplantation and living liver transplantation. The organ transplantation between ABO blood incompatible pair was contra-indication 20 years ago. But now it’s about 27% in living renal transplantation in Japan. Using strong immunosuppressive drugs, after removal of ABO group antibody by plasma exchange, we can perform it easily and safely. For living liver transplantation, the high technic for donor liver operation is necessary. Of course, Japanese transplant surgeon can perform it safely. Both are not so popular in the other countries except for Japan, because the numbers of deceased donors were enough. I report these special situation of Japan in organ transplantation.

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34 Colloid and Interface in Bio-resources and Environment

Research unit colloid engineering in bio-resources Auspices Faculty of Life and Environmental Science International cooperative Educational Program for Creation of a Harmonious Asian Community Electrokinetic kinetic society of Japan

35 Sep 28 (Sun) Special Conference Room

Colloid and Interface in Bio-resources and Environment

Huazhong Agricultural Chair Wengfeng Tan University

Flocculation dynamics of PSL particles with polyelectrolytes - Bridging 11:00-11:20 Yasuhisa Adachi University of Tsukuba vs. charge neutralization-

11:20-11:40 Munehide Ishiguro Hokkaido University Surfactant Adsorption and Transport in a Humic Soil

11:40-12:00 Yuji Yamashita University of Tsukuba Colloidal properties of humic substances

Adsorption of polyanion and anionic surfactant onto large alpha 12:00-12:15 Tien Duc Pham University of Tsukuba alumina beads with positively charged surface

Malaysia-Japan International The Effect of Extraction Process on the Effectiveness of Moringa 12:15-12:30 Wan Khairunnisa Institute of Technology oleifera as a Coagulant

12:30-13:30 Lunch Chair Munehide Ishiguro Hokkaido University

13:30-14:15 Alexander Zezin Moscow State University Interpolyelectrolyte complexes for ecology

Development of the radioactive decontamination techniques using 14:15-14:35 Noriyuki Kumazawa Ibaraki University polymer materials

Aggregation and deposition kinetics of model colloidal particles under 14:35-14:55 Motoyoshi Kobayashi University of Tsukuba the influence of attractive electric double layer force

14:55-15:10 Kenta Yamada University of Tsukuba Amendment Effect of Polyion Complex against Raindrop Erosion

15:10-15:30 Coffee Break Chair Yasuhisa Adachi University of Tsukuba

15:30-16:00 Alexander Yaroslavov Moscow State University Complexes of cationic polymers with anionic liposomes

Layer-by-layer multi-coating of large oil droplets by polyelectrolytic 16:00-16:20 Sosaku Ichikawa University of Tsukuba dietary fibers for the stability control

Intermolecular Interaction observed in Polyelectrolyte Complex 16:20-16:40 Kazuyoshi Ogawa University of Tsukuba Formation Using Microgel

Huazhong Agricultural 16:40-17:00 Wenfeng Tan The complexation of protein and Humic substances University

17:00-17:30 Hiroyuki Ohshima Tokyo University of Science Electrostatic interaction between soft particles

17:30-17:50 Floor discussion

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2 / 26 ページ Sep 28 (Sun) Special Conference Room

Colloid and Interface in Bio-resources and Environment

Huazhong Agricultural Chair Wengfeng Tan University

Flocculation dynamics of PSL particles with polyelectrolytes - Bridging 11:00-11:20 Yasuhisa Adachi University of Tsukuba vs. charge neutralization-

11:20-11:40 Munehide Ishiguro Hokkaido University Surfactant Adsorption and Transport in a Humic Soil

11:40-12:00 Yuji Yamashita University of Tsukuba Colloidal properties of humic substances

Adsorption of polyanion and anionic surfactant onto large alpha 12:00-12:15 Tien Duc Pham University of Tsukuba alumina beads with positively charged surface

Malaysia-Japan International The Effect of Extraction Process on the Effectiveness of Moringa 12:15-12:30 Wan Khairunnisa Institute of Technology oleifera as a Coagulant

12:30-13:30 Lunch Chair Munehide Ishiguro Hokkaido University

13:30-14:15 Alexander Zezin Moscow State University Interpolyelectrolyte complexes for ecology

Development of the radioactive decontamination techniques using 14:15-14:35 Noriyuki Kumazawa Ibaraki University polymer materials

Aggregation and deposition kinetics of model colloidal particles under 14:35-14:55 Motoyoshi Kobayashi University of Tsukuba the influence of attractive electric double layer force

14:55-15:10 Kenta Yamada University of Tsukuba Amendment Effect of Polyion Complex against Raindrop Erosion

15:10-15:30 Coffee Break Chair Yasuhisa Adachi University of Tsukuba

15:30-16:00 Alexander Yaroslavov Moscow State University Complexes of cationic polymers with anionic liposomes

Layer-by-layer multi-coating of large oil droplets by polyelectrolytic 16:00-16:20 Sosaku Ichikawa University of Tsukuba dietary fibers for the stability control

Intermolecular Interaction observed in Polyelectrolyte Complex 16:20-16:40 Kazuyoshi Ogawa University of Tsukuba Formation Using Microgel

Huazhong Agricultural 16:40-17:00 Wenfeng Tan The complexation of protein and Humic substances University

17:00-17:30 Hiroyuki Ohshima Tokyo University of Science Electrostatic interaction between soft particles

17:30-17:50 Floor discussion

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2 / 26 ページ Flocculation dynamics of PSL particles with polyelectrolytes - Bridging vs. charge neutralization -

Lili Feng and Yasuhisa Adachi

Faculty and Graduate school of Life and Environmental Sciences, University of Tsukuba

Flocculation kinetics of negatively charged polystyrene latex particles with high molecular weight linear polyelectrolytes were investigated to identify the mechanism of bridging and charge neutralization, and also steric effects and electrostatic effects. Polyelectrolyte chains of different charge density were applied on purpose. The two mechanisms are confirmed to take places simultaneously under the condition of hydrodynamic mixing. However, under the condition without hydrodynamic mixing, we can identify the feature of two mechanisms. For high charge density polymer, the mechanism of charge neutralization is more important for the system close to practical application. It was confirmed bridging takes places with relatively low charge density polymers near isoelectric point. These results characterized the picture of polyelectrolyte dynamics at colloid interface just after incubation.

38 Surfactant Adsorption and Transport in a Humic Soil

Munehide Ishiguro

Research Faculty of Agriculture, Hokkaido University

Sodium dodecylbenzene sulfonate (DBS) is a very useful and widely used anionic surfactant. This surfactant sometimes creates environmental problems when it is released into the environment. However, the factors influencing the adsorption and transport of DBS in soil have not been studied well. In this study, the influence of the potential at the adsorption site on the adsorption of DBS in a soil was first elucidated by using a theoretical adsorption equation and its transport with adsorption and desorption was evaluated experimentally. The soil was a highly humic soil with a negative charge. The amount of DBS adsorbed was measured with a batch method for different electrolyte concentrations of NaCl at pH 4.5 and 6.5. The adsorption site potential of the soil was obtained with the modified Langmuir adsorption equation. The adsorption of DBS decreased as the electrolyte concentration decreased and as the pH increased because the repulsive electric potential between DBS and the soil increased. These results were confirmed by the obtained adsorption site potential and the measured zeta potential. The difference between the adsorption of DBS with a linear and with a branched carbon chain was also detected, and this difference was related to the free energy of micellization. DBS transport delayed with adsorption. The delay was evaluated by the distribution ratio, R=Q/ θC; C is the surfactant concentration of influent, Q is the adsorption amount per soil volume at C and θ is the volumetric water content. At lower electrolyte and DBS concentrations, DBS decomposition during the transport was observed. Because DBS adsorption is strongly affected by electrolyte concentration and pH, these two factors must be carefully considered to predict the fate of DBS in environmental applications.

39 Colloidal properties of humic substances

Yuji Yamashita

Faculty of Life and Environmental Sciences, University of Tsukuba

Humic substances (HS) are natural organic matter that is commonly found in surface and subsurface water as well as in sediments and soils. As secondary products from the microbial decomposition of plant and remains, HS are organic polymeric composites that have no particular set of elemental composition or chemical structure. It has generally been recognized that HS can easily be associated with other chemicals such as hazardous materials and nutrient salts in the natural environment and consequently can influence their chemical speciation and transport behavior. In order to better understand such mediating roles of HS in natural environments, its property and transport behavior should be totally understood. As secondary products from the microbial decomposition of plant and animal remains, HS are organic polymeric composites that have no particular set of elemental composition or chemical structure. Nevertheless, principles of the colloid and surface chemistry have successfully been applied to elucidate the function of HS. HS is negatively charged as a result of the dissociation of its acidic functional groups; therefore, its polyelectrolyte properties including protonation behavior, electrostatic potential and binding affinity to metal ions have been studied in great detail. The aggregation and dispersion behavior of HA has also been investigated over the years. Several studies have been conducted to understand the transport behavior of HS, which be interpreted in relation to their colloidal properties. The aim of the present study was to review researches of HS in the viewpoint of colloid and surface chemistry and to enhance the importance of the development of study on the physicochemical function of HS.

40 Adsorption of polyanion and anionic surfactant onto large alpha alumina beads with positively charged surface

Tien Duc Pham*, Motoyoshi Kobayashi, Yasuhisa Adachi

Graduate School of Life and Environmental Sciences, University of Tsukuba, Japan

Adsorption of strong polyanion poly(styrene sulfonate), PSS and anionic surfactant, sodium dodecyl sulfate (SDS) onto α-alumina beads with large size was systematically investigated as functions of pH and NaCl concentration. The calculated curves from two-step model can reasonably represent experimental results of PSS and SDS adsorption isotherms onto α-Al2O3.

The adsorption amounts of PSS and SDS onto α-Al2O3 reduce with increasing pH due to the decrease in the initial surface charge of α-Al2O3. The proton adsorption isotherms at low salt concentrations upon surfactant adsorption can also be described well by two-step model, but this cannot be applicable for proton adsorption upon polyelectrolyte adsorption. The adsorption amount of PSS increases with an increase in molecular weight of PSS from 70 to 1000 kg/ mol. It suggested that a more flat conformation for absorbed PSS70 than that of PSS1000. The adsorption amount of PSS increases with increasing salt concentration for both PSS70 and PSS1000, demonstrating that not only electrostatic but also non-electrostatic interactions induce PSS adsorption. The SDS adsorption isotherms at three salt concentrations have a common intersection point (CIP) corresponding to charge neutralization and the adsorption density of SDS onto α-Al2O3 decreases with increasing electrolyte concentration below CIP. Such phenomena, on the contrary, cannot be observed for PSS adsorption. The SDS uptake onto α-Al2O3 in the presence of hemimicelles or admicelles can prevent the adsorption of PSS so that the adsorption of PSS decreases significantly with pre-adsorption of SDS. Furthermore, SDS is able to enhance desorption of PSS dramatically, suggesting that the adsorption of SDS onto α-Al2O3 is stronger than PSS adsorption.

41 The Effect of Extraction Process on the Effectiveness of Moringa oleifera as a Coagulant

Wan Khairunnisa

Malaysia-Japan International Institute of Technology (MJIIT)

The most effective organic coagulant is Moringa oleifera, a multipurpose plant that can be fully utilizes for other purpose as well. The active ingredient inside of M. oleifera seed is the main focus for high performance coagulation process. It is reported that active ingredient also known as coagulant protein. Protein extracted M. oleifera can reduce sludge production and safe towards the operator since the organic sludge is biodegradable, compared to aluminium sulphate, a chemical coagulant. Aluminium sulphate (alum) has greatly used in wastewater treatment of most countries, except rural country such as Africa. Furthermore, Malaysia is known to the high usage of alum in wastewater treatment, same with other developing countries. However, the problem causes by alum has not yet been solved even a new invented chemical coagulant was introduced last 2007. Several methods on protein extraction have established by earlier researcher since 1988, and still in investigation till today. Pressurized water extractor (PWE) is a new instrument that uses green chemical approach, where the water is the main solvent and no chemical is involve. PWE can extract a 100% protein with suitable parameters but unfortunately, no information of PWE had been use on M. oleifera. The main purpose of study is to investigate the effect of extraction process using PWE with coagulation performance of M. oleifera. The temperature ranges from 40°C to 180°C of PWE will be used for optimization of the extraction. The coagulation performances between extraction using PWE and conventional method will be compared. The extraction using PWE is expected to produce extracted protein in high quantity and quality compared to other conventional methods used. Organic coagulant promises better environment compared to chemical coagulant.

42 Interpolyelectrolyte complexes for ecology

A.B.Zezin, V.B.Rogacheva, M.F.Zansokhova, A.A.Yaroslavov

Department of Chemistry, M.V.Lomonosov Moscow State University, Moscow, Russia

There are so many sources of dust of different nature which consists of highly dispersed particles. They form the air sols that are very dangerous for people. The extremely dangerous are those one which contain the toxic substances such as heavy metals or radionuclide’s. The last one is formed in the huge amount as a result of accidents such as at Chernobyl in 1986 and Fukushima in 2011 AER. So it is necessary to suppress the secondary contamination of the top soil via the wind and water erosion. Because of the complex and nonuniform character of the natural dispersed particles sur- face it is natural to search the effective binders for the dispersed systems among the amphi- philic compounds such as interpolyelectrolyte complexes (IPC). They are formed as a result of coupling of oppositely charged polyions. IPC particles are known to contain the coupled hydrophobic blocks and hydrophilic charged entities. They actually proved to be the effective binders of soil particles also for the ability of different kind of units to exchange their positions so that to find the optimal configurations. It was established in the course of fundamental stud- ies of IPC structure and properties. The IPC working compositions are created on the base of water-salt (mineral fertilizers) solutions of various IPC. The technology of IPC formulations usage is that they are deposited on the top soil with the already existing technique such as watering machinery, helicopters and so on. As a result the soil is soaked at the depth of 2-5 mm. The layer formed is the soil- polymer crust which is solid in the dry state and plastic in the wet state. The typical composi- tion successfully used in Chernobyl contained 1-2 % wt. of oppositely charged polyelectrolytes with the consumption 1-2 liters per 1 m2 (10-20 ton per 1 hectare). The same formulations were found to be the effective flocculants for various aqueous mineral highly dispersed systems. The addition of ~ 1 % wt. of anionic microgel to the typical formulation proved to increase significantly the strength of soil-IPC crust. The IPC hydrogels were studied especially and they were shown to form the core-shell type of structures with IPC shell.

The study was supported by the RSF project № 12-03-00705-а

43 Development of the radioactive decontamination techniques using polymer materials

Noriyuki Kumazawa

Department of Biomolecular Functional Engineering,College of Engineering, Ibaraki University

Cesium contamination due to the accident of the Fukushima Daiichi nuclear power plant in 2011 has not yet been resolved today. In this study, we carried out (i) development of the novel remover film made of polyvinyl alcohol (PVA) for radioactive decontamination, (ii) development of the flocculation-precipitation (FP) reagent for the recovery of cesium contaminated clay particles. For the decontamination in low-polluted area, high-pressure water cleaning method have been widely used so far. In this method, however, the scattering of the splashing contaminated water should be avoided. In the decontamination of the building surface, the shot blast method is sometimes used to scrape off the contaminated surface. However, the usage of this technique is limited and the diffusion of polluted dust should be carefully controlled. In this study, we developed a novel film-forming remover solution for the radioactive decontamination by using PVA, surfactant and bentonite, and its performance was investigated. The prepared solution was applied to the building surface such as rooftops. After natural drying, a strippable film was formed which was then peeled off with sticking the surface contaminants. The cesium removal ratio (CRR) was evaluated from the measurement using the surface dosimeter. In the case of concrete surface (Date, Fukushima), the CRR was 40-50%. In the case of acrylic rubber surface (Fukushima University), the CRR was as high as 90%. The radioactive cesium is mostly sorbed to the clay particles in the soil. The clay particles may move from the forest to the city area due to rainfall, which leads to a serious problem of repetitive recontamination. A new FP reagent was developed to realize effective prevention of the recontamination and effective cesium recovery. A new FP reagent made of 3:1 molar ratio of polydiallyldimethylammonium chloride (PDADMAC) and sodium polyacrylate (PAANa) was found to precipitate the clay particles of 57.5g per 1g, which is more than ten times effective compared to the commercially available inorganic FP reagent.

44 Aggregation and deposition kinetics of model colloidal particles under the influence of attractive electric double layer force

Motoyoshi Kobayashi

Faculty of Life and Environmental Sciences, University of Tsukuba

Understanding of aggregation and deposition kinetics of colloidal particles is important to control solid-liquid separation processes and to predict the fate of substances sorbed with natural particles in soil and water environments. Colloidal particles usually have surface charge and form electric double layer (EDL). While the kinetics without EDL force is controlled by the collision frequency as well as hydrodynamic and the van der Waals interactions, the aggregation/deposition rate with EDL force is affected by surface charge and ionic strength as expressed by the theory of Derjaguin, Landau, Verwey, and Overbeek (DLVO). Many studies so far have focused on the effect of repulsive EDL force on the kinetics. In the presence of repulsive EDL force, the rate of aggregation/deposition sharply decreases with decreasing electrolyte concentration and increases with decreasing the magnitude of the surface potential. Such behaviors can be qualitatively described by rate theories with the DLVO force. However, theoretical values quantitatively differ from experimental ones. On one hand, less studies have been carried out for the aggregation/deposition kinetics in the presence of attractive EDL force, which acts between oppositely charged surfaces. In order to improve current knowledge of the rate theories of aggregation/deposition including the DLVO force, we have performed the experimental and theoretical studies on aggregation and deposition of spherical model particles under the influence of attractive EDL. In our experiments, rates of Brownian aggregation between silica and amidine latex and turbulent aggregation rates between sulfate latex and amidine latex were obtained. Experiments of deposition of latex particles were conducted in the packed bed of zirconia beads. Using these materials allows us to examine the influence of surface potential on aggregation/deposition. Experimental results demonstrate that aggregation and deposition rates increase slowly with decrease of salt concentration and the effect of the magnitude of surface potential is weak. The DLVO theory reasonably describes experimental trends.

45 Amendment Effect of Polyion Complex against Raindrop Erosion

Kenta YAMADA1, Motoyoshi KOBAYASHI2, Haruyuki FUJIMAKI3

1Graduate School of Life and Environmental Sciences, University of Tsukuba 2Faculty of Life and Environmental Sciences, University of Tsukuba 3Arid Land Research Center, Tottori University, Japan

We examined the preventing effect of polyion complex (PIC) against raindrop erosion on soil surface using the rainfall simulator and a compact soil box. The used PIC solution was composed of polycation (Polydiallyldimethylammonium chloride), polyanion (polyacrylic acid) electrolyte (KNO3) and pH adjuster (KOH). The Tottori masa soil was packed into an acrylic box. Upper and lower bottoms of the box had 40 holes of 5 mm in diameter so that infiltrated water can be drained through the holes. The soil in a box was saturated with tap water from the bottom. Then, the mixed solution was applied to the soil surface under three different of PIC solution doses 0, 1, 3 L m-2. The runoff was collected from an outlet port located at the downstream edge every 10 minutes. The volume of runoff and the mass of washed soil were measured. The rainfall duration was 120 minutes, and the rainfall intensity was about 70 mm h-1. This intensity was very low compared with the hydraulic conductivity of the saturated soil. Therefore the occurrence of runoff means the change of soil structure; a crust layer forms. The experimental results clearly show that the cumulative runoff and the cumulative soil loss were affected by the applied amount of the mixed solution. That is, the runoff and the soil loss decrease with increasing the amount of applied mixed solution. It is said that runoff is brought about by decreased hydraulic conductivity resulted from crust formation on soil surface, and soil loss is generated by soil detachment and subsequent transport of soil particles by raindrop impact and surface runoff flow. Therefore our results suggest that insoluble PICs, which are formed by decreasing of salt concentration due to rainfall, act as a binding agent between the soil particles, then stabilize soil structure.

46 Complexes of cationic polymers with anionic liposomes

A.Yaroslavov, A.Sybachin, O.Zaborova, A.Efimova, E.Yaroslavova, A.Rakhnyanskaya

Department of Chemistry, M.V.Lomonosov Moscow State University, Russia

Composition and properties of complexes are discussed, formed by cationic polymers and anionic lipid vesicles (liposomes). The complexation can be accompanied by structural re-arrangements in the liposomal membranes: lateral lipid segregation, highly accelerated transmembrane migration of lipid molecules, incorporation of adsorbed polymers into the li- posomal membrane, etc., and morphological changes in liposomes: their aggregation, fusion and disruption. Electrostatically adsorbed polycations can be completely removed from the membrane surface in water-salt solutions or in the presence of an anionic polymer. The above mentioned phenomena have been examined depending on the cationic polymer architecture, content of charged lipids, vesicle phase state and size; as well as ionic strength of solution. It is likely that the observations we made might be useful to interpret biological effects of poly- electrolytes and multicharged polymeric constructs and to fabricate functional multiliposomal containers.

47 Layer-by-layer multi-coating of large oil droplets by polyelectrolytic dietary fibers for the stability control

Sosaku Ichikawa

Faculty and Graduate school of Life and Environmental Sciences, University of Tsukuba

Oil-in-water (O/W) emulsion is a dispersion system, in which oil droplets are dispersed in an aqueous dispersion medium. It has been widely used in food and pharmaceutical industries. However, it is desirable to control the stability of oil droplets for the protection of bioactive lipophilic components during the storage and their targeted release in a gastrointestinal tract. In this study, we modified the surface properties of large oil droplets larger than 10 micrometer in size by electrostatic layer-by-layer multi-coating using polyelectrolytic dietary fibers, aiming to control their stability. Monodisperse O/W emulsion was by microchannel emulsification. The mean droplet diameter and coefficient of variation were 26.9 micrometer and 6.5%, respectively. Chitosan (CHI) as a cationic dietary fiber and carboxymethyl cellulose (CMC) as an anionic fiber were alternately coated onto oil droplet surface. The zeta-potential of oil droplets was alternately changed, depending on the net charge of droplets dominated by the electrostatic property of the outer fiber layer. Multi-coated oil droplets did not aggregate or coalescence in an emulsifier-free aqueous medium after two weeks storage at room temperature. When CHI was modified outer layer, oil droplets were unstable at high pH value (pH > 6), due to loss of CHI charge. When CMC was outer layer, the oil droplets showed good stability to aggregation in between pH 5 and 9, but aggregated at lower pH value (pH < 5), due to loss of CMC charge. These findings indicated that large oil droplet stability can be controlled by layer-by-layer coating using food grade polyelectrolytes.

48 Intermolecular Interaction observed in Polyelectrolyte Complex Formation Using Microgel

Kazuyoshi Ogawa

Faculty of Life and Environmental Sciences, University of Tsukuba

Polyelectrolyte complexes are formed by the interaction between oppositely charge polyelectrolytes. Considering that biopolymers such as protein and DNA are polyelectrolytes, interpolyelectrolyte complex (IPEC) formation could be regarded as a simple model of assembly- phenomena of molecules observed in biological system. In the self assembly-phenomena of molecules, intermolecular interaction such as electrostatic interaction, hydrophobic interaction, and hydrogen bonding plays an important role. The various materials of polyelectrolyte have been used in order to investigate the mechanism of IPEC. In our studies on IPEC, responsive polymer microgel has been used as sample (or material). Responsive polymer microgel demonstrates not only swelling-deswelling behavior but also aggregation-dispersion one in response to the change of solution pH, temperature, salt concentration etc. These behaviors occur due to change of intra- and inter particle interaction. Through these behavior of microgel observed by light scattering, we investigated how salt concentration effect on electrostatic interaction and hydrophobic one. In addition we investigated intermolecular interaction during IPEC in which charged polymers interact with oppositely charged microgels. The resulting complexes are then divided into three types: (i) water-soluble intraparticle complexes consisting of a microgel to which linear polyelectrolytes bind (ii) complex coacervates, and (iii) insoluble amorphous precipitates. The type of resulting complex depends on ionic strength as well as mixing ratio, which affects on intermolecular interaction in IPEC. These results obtained would help not only understanding self assembly-phenomena of molecules observed in bio-system but also the technology of layer-by-layer, microencapsulation, and design of nanoparticle for drug delivery system using intermolecular interaction.

49 The complexation of protein and Humic substances

Wenfeng Tan1, Yan Li1, Mingxia Wang1 and Luuk Koopal2

1College of Resources and Environment, Huazhong Agricultural University, China 2Department of Physical Chemistry and Colloid Science, Wageningen University, the Netherlands

Humic substances (HS), including humic acids (HA) and fulvic acids (FA), are important components of soil systems. The reaction between enzymes and soluble humic matter has been attributed to co-polymerisation, adsorption and encapsulation of enzymes into the inner structure of humic matter. The importance of electrostatic and hydrophobic interactions between humic acids and proteins concluded that parameters like mixing ratio of HA and protein, pH and ionic strength determined the extent of HA-protein complexation and aggregation of the complexes. Complexation of oppositely charged HS and protein is a form of ‘complex coacervation’ or ‘associative phase separation’, a well-known liquid-liquid phase separation driven by the association of two oppositely charged macromolecules. HS form strong complexes with oppositely charged proteins, which will lead to changes in the enzyme activity. The effect of soil HS on the activity and stability of two enzymes was investigated as a function of pH, ionic strength and mass ratio HS/enzyme. Humic acid (JGHA) and fulvic acid (JGFA) are negatively charged, lysozyme is net positive at pH values below 10.4 and urease is net positive below pH 5.2 or net negative above pH 5.2. The enzyme activities in the HS-enzyme complexes were suppressed when the enzymes were oppositely charged to the HS. The largest activity suppression was observed around the mass ratio HS/enzyme where the HS-protein complex was at its isoelectric point (IEP). At the IEP strong aggregation of the complexes led to encapsulation of the enzyme. The ionic strength was important; an increase decreased complex formation, but increased aggregation. Due to the larger hydrophobicity of JGHA than JGFA, the reduction in enzyme activity was stronger for JGHA. The enzyme stability decreased also maximally at mass ratio around the IEP of the complex when HS and protein were oppositely charged. When urease and HS were both negatively charged no complexes were formed, but the presence of JGHA or JGFA improved the activity and stability of the enzyme (Tan WF et al., J Colloid Interface Sci, 2014, 430: 40-46; Li Y et al., Environ Sci Technol, 2013, 47: 5050-5056).

50 Electrostatic interaction between soft particles

Hiroyuki Ohshima

Faculty of Pharmaceutical Sciences, Tokyo University of Science

Electrostatic interactions between soft particles (i.e., hard particles covered with an ion- penetrable surface layer of polyelectrolytes) in an electrolyte solution are quite different from those for hard particles without surface structures. The remarkable difference is that the elec- trostatic interactions between soft particles are governed by their space-charges distributed within the particles or the Donnan potentials, while those for hard particles are determined by their surface charges or surface potentials. Theoretical studies on the interaction between soft particles so far have focused mostly on the interactions before contact of the surface layers of interacting soft particles (Ohshima H., Theory of Colloid and Interfacial Electric Phenomena. Elsevier, 2006; Ohshima, H., Biophysical Chemistry of Biointerfaces, John Wiley & Sons, 2010). There are only a few studies on the electrostatic interaction between soft particles after contact. Here we discuss the effects of compression and interdigitation of the polyelectrolyte segments in the surface layers of two interacting parallel soft plates (Ohshima H., Colloid Polym Sci 292: 431-439, 2014). In this model the interaction process consists of three stages, i.e., interaction before contact of the polyelectrolyte layers (stage 1), interdigitation (stage 2), and compression (stage 3). We also discuss the interaction of two interpenetrating soft par- ticles (Ohshima H., Colloids Surf. A., in press, 2014). A three-stage model of the electrostatic interaction between two interpenetrating charged spherical soft particles with no particle core (space-charged porous spheres) in an electrolyte solution is presented. That is, (i) interaction before contact of the two spheres, (ii) partial interpenetration, and (iii) full interpenetration, i.e., engulfing of one sphere by the other. Finally, we consider three-dimensional discrete charge effects on the electrostatic interaction between soft particles (Ohshima H., Colloid Polym Sci 292: 757-761, 2014).

51 NOTE

52 Aging Sciences

Faculty of Medicine, University of Tsukuba Ph.D. Program in Human Biology, University of Tsukuba International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba Faculty of Life and Environmental Sciences, University of Tsukuba

53 Sep 28 (Sun) International Conference Room

Aging Sciences

Chair Mamiko Sakata University of Tsukuba Chair Takahiro Kojima Univeristy of Tsukuba

13:10-13:35 Daniel S. Peeper Netherlands Cancer Institute In vivo RNAi dropout screens for cancer drug target discovery

Mamiko Sakata- Premalignant and disease-specific mutations in age-related 13:35-14:00 University of Tsukuba Yanagimoto hematologic malignancies

14:00-14:25 Liran Shlush University Health Network Preleukemia clonal hematopoiesis and the aging bone marrow

Development of redox polymer nanomedicine for anti-aging 14:25-14:50 Yukio Nagasaki University of Tsukuba treatments

University of Pittsburgh School Age-related urinary bladder dysfunction: involvement of the 14:50-15:15 Naoki Yoshimura of Medicine angiotensin II receptor system

15:15-15:40 Hiromitsu Negoro Kyoto University Coordination of day-night changes in urination by the circadian clock

15:40-15:55 Coffee Break Chair Yu Hayashi University of Tsukuba Chair Kaspar Vogt University of Tsukuba University of Texas 15:55-16:20 Joseph S. Takahashi Molecular architecture to the circadian clock in mammals Southwestern Medical Center

16:20-16:45 Joseph Bass Northwestern University Epigenetic regulation by the molecular clock-sirtuin pathway

16:45-17:10 Yu Hayashi University of Tsukuba How the brain generates REM sleep

17:10-17:35 Emmanuel Mignot Stanford University Narcolepsy and genetic predisposition

A conserved bicycle model for circadian clock control of membrane 17:35-18:00 Ravi Allada Northwestern University excitability

Sep 29 (Mon) Hall Chair Hisashi Oishi University of Tsukuba Chair Pleasantine Mill University of Edinburgh Genetic and biochemical characterization of mammalian cilia 9:00-9:25 Pleasantine Mill University of Edinburgh compartmentalization

9:25-9:50 Hiroaki Nakano University of Tsukuba Strange and simple placozoans- ‘biologically immortal’ ?

Mechanisms of haematopoietic stem cell development in mouse and 9:50-10:15 Alexander Medvinsky University of Edinburgh human 10:15-10:30 Coffee Break Chair Hiroshi Suzuki University of Tsukuba Chair Peter ten Dijke Leiden University Medical Leiden University Medical 10:30-10:55 Peter ten Dijke TGF-β receptor signaling in breast cancer cell invasion and metastasis Center

The role of the thymus in modulating γδ T cell suppressor activity 10:55-11:20 Auro Nomizo University of Sao Paulo during experimental Trypanosoma cruzi infection

Regulation of cancer stem cell potential by HMGA2, a chromatin 11:20-11:45 Aristidis Moustakas Uppsala University regulator of epithelial-mesenchymal transition and biological aging

11:45-12:10 Shu-Chun Teng National Taiwan University Telomerase activation in yeast and cancer cells

54

16 / 26 ページ Sep 28 (Sun) International Conference Room

Aging Sciences

Chair Mamiko Sakata University of Tsukuba Chair Takahiro Kojima Univeristy of Tsukuba

13:10-13:35 Daniel S. Peeper Netherlands Cancer Institute In vivo RNAi dropout screens for cancer drug target discovery

Mamiko Sakata- Premalignant and disease-specific mutations in age-related 13:35-14:00 University of Tsukuba Yanagimoto hematologic malignancies

14:00-14:25 Liran Shlush University Health Network Preleukemia clonal hematopoiesis and the aging bone marrow

Development of redox polymer nanomedicine for anti-aging 14:25-14:50 Yukio Nagasaki University of Tsukuba treatments

University of Pittsburgh School Age-related urinary bladder dysfunction: involvement of the 14:50-15:15 Naoki Yoshimura of Medicine angiotensin II receptor system

15:15-15:40 Hiromitsu Negoro Kyoto University Coordination of day-night changes in urination by the circadian clock

15:40-15:55 Coffee Break Chair Yu Hayashi University of Tsukuba Chair Kaspar Vogt University of Tsukuba University of Texas 15:55-16:20 Joseph S. Takahashi Molecular architecture to the circadian clock in mammals Southwestern Medical Center

16:20-16:45 Joseph Bass Northwestern University Epigenetic regulation by the molecular clock-sirtuin pathway

16:45-17:10 Yu Hayashi University of Tsukuba How the brain generates REM sleep

17:10-17:35 Emmanuel Mignot Stanford University Narcolepsy and genetic predisposition

A conserved bicycle model for circadian clock control of membrane 17:35-18:00 Ravi Allada Northwestern University excitability

Sep 29 (Mon) Hall Chair Hisashi Oishi University of Tsukuba Chair Pleasantine Mill University of Edinburgh Genetic and biochemical characterization of mammalian cilia 9:00-9:25 Pleasantine Mill University of Edinburgh compartmentalization

9:25-9:50 Hiroaki Nakano University of Tsukuba Strange and simple placozoans- ‘biologically immortal’ animals?

Mechanisms of haematopoietic stem cell development in mouse and 9:50-10:15 Alexander Medvinsky University of Edinburgh human 10:15-10:30 Coffee Break Chair Hiroshi Suzuki University of Tsukuba Chair Peter ten Dijke Leiden University Medical Leiden University Medical 10:30-10:55 Peter ten Dijke TGF-β receptor signaling in breast cancer cell invasion and metastasis Center

The role of the thymus in modulating γδ T cell suppressor activity 10:55-11:20 Auro Nomizo University of Sao Paulo during experimental Trypanosoma cruzi infection

Regulation of cancer stem cell potential by HMGA2, a chromatin 11:20-11:45 Aristidis Moustakas Uppsala University regulator of epithelial-mesenchymal transition and biological aging

11:45-12:10 Shu-Chun Teng National Taiwan University Telomerase activation in yeast and cancer cells

55

16 / 26 ページ Sep 30 (Tue) International Conference Room Chair Ryosuke Niwa University of Tsukuba Chair Tang-Long Shen National Taiwan University Steroid hormones and aging: lesson from the fruit fly Drosophila 9:00-9:25 Ryosuke Niwa University of Tsukuba melanogaster

Long live the queen – the molecular and endocrine underpinnings of 9:25-9:50 Klaus Hartfelder University of Sao Paulo the reproduction/lifespan paradox in social

Nutrient-dependent regulation of steroid hormone biosynthesis in the 9:50-10:15 Yuko Shimada-Niwa University of Tsukuba puberty of fruit fly Drosophila melanogaster Impact of n-3 polyunsaturated fatty acid deficiency on 10:15-10:40 Pierre Trifilieff University of Bordeaux mesoaccumbens dopaminergic transmission and motivation: relevance for the negative symptoms of schizophrenia 10:40-10:55 Coffee Break Chair Masayuki Matsumoto University of Tsukuba Chair Jacques Micheau University of Bordeaux

10:55-11:20 Andreas Zimmer University of Bonn Δ9-THC restores age-related changes in the brain

11:20-11:45 Jacques Micheau University of Bordeaux Effects of acute stress on memory processes

Midbrain dopamine neurons are divided into anatomical subgroups 11:45-12:10 Masayuki Matsumoto University of Tsukuba encoding distinct signals

12:10-12:35 Vincent Dousset University of Bordeaux Imaging of iatrogenic dysimmunity

12:35-13:00 Elena Avignone University of Bordeaux Activation of microglia impacts their directional motility

Sep 30 (Tue) International Conference Room Chair Emiko Noguchi University of Tsukua Chair Han-Yi E. Chou National Taiwan University Federal University of Sao Post-translatinal modification by small ubiquitin-modifier SUMO in the 13:30-13:55 Renata Rosito Tonelli Paulo cell biology of Giardia lamblia

Interaction of small viral capsids with the nuclear pore - they are no 13:55-14:20 Michael Kann University of Bordeaux classical cargo

Novel ‘in situ’ preparation of zinc finger nucleases based on Ni(II)- 14:20-14:45 Bela Gyurcsik University of Szeged induced specific hydrolysis of proteins

14:45-15:10 Kyoko Yokomori University of California, Irvine Real time analyses of the DNA damage response in mammalian cells

Identification of disease-casing variants using next generation 15:10-15:35 Emiko Noguchi Univerity of Tsukuba sequencing 15:35-15:50 Coffee Break Chair Takashi Mizuhiki University of Tsukuba Chair Erick L. Bastos University of Sao Paulo

15:50-16:15 Erick Leite Bastos University of Sao Paulo Biocompatible antiradicals inspired by fluorescent flowers

16:15-16:40 Frank Herbert Quina University of Sao Paulo The Anthocyanins: plant pigments with multiple functions in nature

Genome-wide remodeling of long-range interactions during skeletal 16:40-17:05 Ali Mortazavi University of California, Irvine muscle differentiation

University of Sao Paulo, Metabolomics and in silico tools in the search of natural compounds 17:05-17:30 Fernando B. Da Costa Ribeirao Preto from plants with anti-inflammatory potential

17:30-17:55 Arthur D. Lander University of California, Irvine Design principles of biological growth control

56

17 / 26 ページ Sep 30 (Tue) International Conference Room Chair Ryosuke Niwa University of Tsukuba In vivo RNAi dropout screens for cancer drug target discovery Chair Tang-Long Shen National Taiwan University Steroid hormones and aging: lesson from the fruit fly Drosophila 9:00-9:25 Ryosuke Niwa University of Tsukuba melanogaster Daniel S. Peeper Long live the queen – the molecular and endocrine underpinnings of 9:25-9:50 Klaus Hartfelder University of Sao Paulo the reproduction/lifespan paradox in social insects Netherlands Cancer Institute Nutrient-dependent regulation of steroid hormone biosynthesis in the 9:50-10:15 Yuko Shimada-Niwa University of Tsukuba puberty of fruit fly Drosophila melanogaster Impact of n-3 polyunsaturated fatty acid deficiency on 10:15-10:40 Pierre Trifilieff University of Bordeaux mesoaccumbens dopaminergic transmission and motivation: relevance for the negative symptoms of schizophrenia In addition to oncogenic drivers, also the ‘non-oncogenome’ can be functionally mined 10:40-10:55 Coffee Break for specific cancer vulnerabilities. Although such screenings are commonly done in vitro, it Chair Masayuki Matsumoto University of Tsukuba Chair Jacques Micheau University of Bordeaux is evident that specific in vivo parameters influence both tumor behavior and therapeutically

10:55-11:20 Andreas Zimmer University of Bonn Δ9-THC restores age-related changes in the brain amenable dependencies. Therefore, we performed parallel in vitro and in vivo negative se- lection shRNA screens to identify factors preferentially necessary to drive tumor expansion. 11:20-11:45 Jacques Micheau University of Bordeaux Effects of acute stress on memory processes Until recently, most advanced stage melanomas were refractory to the available therapeutic op- Midbrain dopamine neurons are divided into anatomical subgroups 11:45-12:10 Masayuki Matsumoto University of Tsukuba tions, but there are encouraging developments. For example, BRAFV600E, a common driver encoding distinct signals in melanoma, can be targeted by specific inhibitors, which causes unprecedented melanoma 12:10-12:35 Vincent Dousset University of Bordeaux Imaging of iatrogenic dysimmunity regression. However, relapse eventually occurs, necessitating the development of combinato- rial therapies. Thus, we performed these function-based screens in melanoma. The results of 12:35-13:00 Elena Avignone University of Bordeaux Activation of microglia impacts their directional motility these in vivo cancer drug target discovery approaches will be discussed. Sep 30 (Tue) International Conference Room Chair Emiko Noguchi University of Tsukua Chair Han-Yi E. Chou National Taiwan University Federal University of Sao Post-translatinal modification by small ubiquitin-modifier SUMO in the 13:30-13:55 Renata Rosito Tonelli Paulo cell biology of Giardia lamblia

Interaction of small viral capsids with the nuclear pore - they are no 13:55-14:20 Michael Kann University of Bordeaux classical cargo

Novel ‘in situ’ preparation of zinc finger nucleases based on Ni(II)- 14:20-14:45 Bela Gyurcsik University of Szeged induced specific hydrolysis of proteins

14:45-15:10 Kyoko Yokomori University of California, Irvine Real time analyses of the DNA damage response in mammalian cells

Identification of disease-casing variants using next generation 15:10-15:35 Emiko Noguchi Univerity of Tsukuba sequencing 15:35-15:50 Coffee Break Chair Takashi Mizuhiki University of Tsukuba Chair Erick L. Bastos University of Sao Paulo

15:50-16:15 Erick Leite Bastos University of Sao Paulo Biocompatible antiradicals inspired by fluorescent flowers

16:15-16:40 Frank Herbert Quina University of Sao Paulo The Anthocyanins: plant pigments with multiple functions in nature

Genome-wide remodeling of long-range interactions during skeletal 16:40-17:05 Ali Mortazavi University of California, Irvine muscle differentiation

University of Sao Paulo, Metabolomics and in silico tools in the search of natural compounds 17:05-17:30 Fernando B. Da Costa Ribeirao Preto from plants with anti-inflammatory potential

17:30-17:55 Arthur D. Lander University of California, Irvine Design principles of biological growth control

57

17 / 26 ページ Premalignant and disease-specific mutations in age-related hematologic malignancies

Mamiko Sakata-Yanagimoto1 and Shigeru Chiba1,2

1Department of Hematology, Faculty of Medicine, University of Tsukuba 2Life Science Center, Tsukuba Advanced Research Center, University of Tsukuba

Aging is associated with genetic and epigenetic dysregulation. Cause of various human diseases is attributed to such a genetic and epigenetic predisposition by aging. Recent sequencing technologies identified the frequent mutations in TET2, DNMT3A, and IDH1/2 genes, encoding epigenetic regulators, in various hematologic malignancies. These gene mutations are also identified in peripheral T-cell lymphomas (PTCL), an age-related hematologic malignancy, especially in those that the tumor cells have features of follicular helper T cells. It has further been demonstrated that the mutations in these genes exist even in premalignant cells as well as tumor cells both in myeloid and lymphoid malignancies. Then, why do these gene mutations provoke various hematologic malignancies? By comprehensive gene-mutation analysis, we found that disease-specific mutations, co-existing with the common gene mutations, might determine the subtypes of hematologic malignancies. In myeloid malignancies, mutations in various genes, including N-RAS, JAK2, RUNX1, C/ EBPalpha, c-Cbl, and splicing machineries, have been identified since 1980s. We identified novel recurrent RHOA mutations in around 60-70% of PTCL samples with features of follicular helper T cells, in a highly disease-specific manner, together with the TET2, DNMT3A, and IDH2 gene mutations shared by various hematologic malignancies (Sakata-Yanagimoto M, et al, Nature Genetics 2014). Myeloid-specific gene mutations were not identified in PTCL. RHOA is a small GTPase, cycling between an active GTP-bound form and an inactive GDP- bound form. Almost all the RHOA mutations found in PTCL were restricted to c.G50T, p.G17V. The G17V RHOA mutant is not able to bind GTP and further inhibits function of the wild-type RHOA. The RHOA mutations are only found in the tumor cells and not found in the premalignant cells, while TET2-and/or DNMT3A mutations are also found in premalignant cells. These data suggest that the RHOA mutations finally occur in TET2-and/or DNMT3A- mutated premalignant cells and provoke a specific type of cancer.

58 Preleukemia clonal hematopoiesis and the aging bone marrow

Liran Shlush

University Health Network

Recent evidence suggests that although de-novo AML presents as an acute condition, the disease has a long evolution (probably years) as a subclinical entity. This is based on the detection of genetic mutations in genes such as DNMT3a that are characteristic of AML, in ostensibly normal hematopoietic cells. Furthermore, these phenotypically normal primitive and mature cell populations carry only a subset of the mutations found in the patient’s leukemic cells at diagnosis, and persist in functionally normal cells in remission. Mutant DNMT3a (DNMT3amut) has been reported at a frequency of ~1 in 1500 individuals with no known hematologic problems, consistent with its occurrence as a preleukemic lesion. Mutations in other leukemia-associated genes such as TET2 have been reported in elderly females who have clonal hematopoiesis but no abnormalities in blood cell production. As humans age a decrease in the repertoire of B and T cells can be observed consistent with decreasing number of stem cells contributing to hematopoiesis. A recent analysis of somatic mutations in the blood of a centenarian (115 years old) demonstrated oligoclonal contribution to hematopoiesis. The distribution of variant allele frequencies suggested that the majority of the peripheral white blood cells were offspring of two related hematopoietic stem cell (HSC) clones. Reports from young rhesus macaques estimated that during a year of follow-up at least 1000 genetically different HSCs clones contributed to hematopoiesis, namely polyclonal contribution under steady state conditions in young non-human primates. This process of decreased number of genetically different HSCs contributing to hematopoiesis can be explained by loss of self-renewing primitive stem cells, or by selection of the fittest clones. As we age HSC environment changes. MRI studies demonstrate increase in yellow marrow (inactive marrow with predominantly fat cells) that peaks in the third decade and a parallel decline in red marrow (active marrow). Under the changing environment stem cells can either die or get selected. HSCs that can maintain regenerative capacity under the changing environment will take over. Evidance suggests that both decreased self-renewal and selection occur as human age. Self-renewal capacity has decreased with age in mice serial transplantation and competitive assays. Human HSCs isolated from elderly in most instances cannot engraft an immunedeficient mouse, while stem cells from cord blood can. The outcomes of allogeneic stem cell transplantation are worse from older donors. It is not clear whether the number of functional stem cells is decreasing or their ability to regenerate is damaged. The recent identification of preL-HSCs by us and others provide evidence that although for most of the aging population stem cell regenerative capacity and self-renewal are decreasing with age, some stem cells gain a selective advantage by acquiring mutations in the epigenetic machinery. Altogether these findings support a paradigm in which a hostile environment

59 selects for adapted stem cells that in time due to the accumulation of other traits can transform into disease producing preleukemic cells. The mechanisms related to preleukemia progression are closely related to the environment. Of note, a recent report describes the development of donor-derived leukemia in a patient 27 months after receiving allogeneic HSCs from an HLA- matched sibling, whose donated peripheral blood cells were later found to carry mutations in IDH2 andDNMT3A at low frequency48. Interestingly, the donor remains free of leukemia 10 years after his stem-cell donation, indicating that the mechanisms underlying the progression from subclinical pre-leukemic hematopoiesis to overt leukemia are complex and context- dependent.

60 Development of redox polymer nanomedicine for anti-aging treatments

Yukio Nagasaki

Department of Materials Science, Graduate School of Pure and Applied Sciences, Master’s School of Medical Sciences, Graduate School of Comprehensive Human Sciences and Satellite Laboratory, International Center for Materials Nanoarchitectonics (WPI-MANA), National Institute of Materials Science (NIMS), University of Tsukuba, Tsukuba, Ibaraki

An oxidative stress, where excess reactive oxygen species (ROS) are produced, is well known to be closely related to not only aging but also development of numerous diseases such as cancer, stroke, myocardial infarction, inflammatory bowel disease (IBD), kidney failure, arteriosclerosis, diabetes, rheumatoid arthritis, Parkinson’s disease, and Alzheimer’s disease. ROS are produced by cellular respiration, normal metabolism, and xenobiotic exposure. Most ROS are generated in cells by the mitochondrial respiratory chain. At the physiological low levels of ROS, they function as important redox messengers in intracellular signaling and regulation. Living organisms consistently maintain a balance between the production of ROS and the effectiveness of antioxidant-protective systems including vitamin C, vitamin E, glutathione, and antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase, and so forth. However, under a state of oxidative stress, free radical production increases remarkably, and the endogenous antioxidants fail to scavenge all ROS, resulting in severe injury. ROS can directly damage cellular components such as lipids, DNA, and proteins by oxidation, thereby increasing the risk of potentially life-threatening disorders. One of the most plausible ways to prevent these oxidative stress injuries is the administration of an exogenous ROS scavenger. Currently, many ROS scavenging compounds have been reported. Most of these compounds are synthetic and/or natural low-molecular-weight (LMW) compounds. However, LMW antioxidants can spread entire body and eliminate important ROS. We have recently been investigating our redox reactive polymers as “Novel Redox Polymer Therapeutics”. Because the polymers and their self-assembles hardly internalize in healthy cells, they scavenge excessive generated ROS selectively. So far, we have confirmed that our redox polymer showed extremely high efficiencies to several oxidative injuries such as Alzheimer’s disease, renal, cerebral and myocardial ischemia-reperfusion injuries, cancers and ulcerative colitis. Our redox polymers can also be applied for biomaterials with low oxidative stress.

61 Age-related urinary bladder dysfunction: Involvement of the angiotensin II receptor system

Naoki Yoshimura1 and Kenichi Mori1,2

1Department of Urology, University of Pittsburgh School of Medicine 2Department of Urology, Oita University Faculty of Medicine

Lower urinary tract symptoms (LUTS), both storage and voiding ones that include urinary urgency, frequency and incontinence, and a difficulty in urination with increased post-void residual volume, respectively, increase as age progresses. Also, urodynamic studies in elderly people often show both overactive and underactive bladder conditions, which are also called “detrusor hyperreflexia with impaired contractility (DHIC)”. Although the etiology of LUTS is multifactorial, our recent study suggested a role of the angiotensin II receptor system in age- related bladder dysfunction. Angiotensin II is reportedly involved in the bladder remodeling, and exerts its effects through angiotensin II type 1 (AT1) and type 2 receptors (AT2). Cystometric analysis of 8 weeks-old (8W) and 15 months-old (15M) female SD rats revealed that pressure threshold (PT), post-void residual volume (RV) and the number of non-voiding contractions (NVCs) were significantly increased in 15M vs. 8W rats (P<0.05) and that maximum voiding pressure (MVP) was significantly decreased in 15M rats compared to 8W rats (P<0.05). In bladder tissues, the protein and mRNA expression of AT1, connexin 43 (Cx43), ERK-MAPK, and collagen I were significantly increased in 15M rats compared to 8W rats (P<0.05). AT2, PPAR-γ, adiponectin and adiponectin receptor-1 were also significantly increased in 15M vs. 8W rats. Furthermore, the relative expression ratio of AT1 protein against AT2 protein in the mucosa and detrusor was significantly higher in 15M vs. 8W rats. These results suggest that the upregulation of AT1, which overcomes AT2 upregulation, may play a significant role in bladder overactivity (i.e., NVCs) due to increased Cx43 expression via activation of MAPK signaling pathways as well as in incomplete emptying and underactive bladder due to increased collagen I expression during aging. Thus, the alteration in AT1-mediated angiotensin system could contribute to age-related LUTS including storage and voiding ones, which are often seen as DHIC in aged patients.

62 Coordination of day-night changes in urination by the circadian clock

Hiromitsu Negoro1, Akihiro Kanematsu2 and Osamu Ogawa1

1Department of Urology, Kyoto University Graduate School of Medicine 2Department of Urology, Hyogo College of Medicine

Urinary frequency in mammals decreases during sleep period and increases during wake period. This phenomenon is determined by triad factors; decreased arousal level in the brain, decreased urine production rate from the kidneys, and increased functional bladder capacity during sleep. Recently, daily rhythms of physiology and behavior have been known to be modulated by the circadian clock system, such as the sleep wake cycle, hormonal secretion, body temperature, blood pressures and so on. The circadian clock (‘the clock’) consists of a number of clock genes and is driven by molecular genetic transcription-translation feedback machinery. The clock exists in most organs and cells, termed ‘peripheral clock’, which is orchestrated by the central clock in the suprachiasmatic nucleus of the brain. Thousands of genes of such organs, about 5 to 15% of total genes, are oscillating in a circadian manner. Several of these genes could be involved in generation of day-night changes in urination; in the kidney, they are genes involved in excretion and reabsorption of water and major electrolytes, or in modulation of renal vascular tone, and in the bladder, genes associated with regulation of biological process and response to stimulus, including connexin 43, a gap-junction protein that enhances transmission of neural stimuli in muscle cells. In this session, the linkage between the day-night changes in urinary frequency and the genetic rhythm maintained by the clock system will be discussed, focusing on brain, kidney and especially bladder. Such linkage presents a novel paradigm for investigating the pathophysiology of nocturnal enuresis (bed wetting in children), considered as immaturity in development of the rhythm, and nocturia (frequent urination at night in the elderly), considered as loss of the rhythm. (Negoro H, Kanematsu A, Doi M et al Nat Commun 3:809 2012, Negoro H, Kanematsu A, Yoshimura K and Osamu O J Urol 190(3):843-849 2013.

63 Molecular architecture to the circadian clock in mammals

Joseph S. Takahashi, Ph.D.

Howard Hughes Medical Institute, Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA

The circadian clock mechanism in animals involves an autoregulatory transcriptional feedback loop in which CLOCK and BMAL1 activate the transcription of the Period and Cryptochrome genes. The PERIOD and CRYPTOCHROME proteins then feedback and repress their own transcription by interaction with CLOCK and BMAL1. We have studied the biochemistry of the CLOCK:BMAL1 transcriptional activator complex as well as the genomic targets of CLOCK and BMAL1 using ChIP-seq methods. We describe the dynamics of the core circadian clock transcriptional system. CLOCK and BMAL1 interact with the regulatory regions of thousands of genes. The gene network and dynamics of the system will be discussed. A mechanistic description of the core circadian clock mechanism should promote our understanding of how the circadian clock system influences behavior, physiology and behavioral disorders.

References 1. Bass, J. and J.S. Takahashi. 2010. Circadian integration of metabolism and energetics. Science 330: 1349-1354. PMCID: 3756146. 2. Huang, N., Y. Chelliah, Y. Shan, C.A. Taylor, S.-H. Yoo, C. Partch, C.B. Green, H. Zhang and J.S. Takahashi. 2012. Crystal structure of the heterodimeric CLOCK:BMAL1 transcriptional activator complex. Science 337: 189-194. PMCID: 3694778. 3. Koike, N., S.H. Yoo, H.C. Huang, V. Kumar, C. Lee, T.K. Kim and J.S. Takahashi. 2012. Transcriptional architecture and chromatin landscape of the core circadian clock in mammals. Science 338: 349-354. PMCID: 3694775.

64 Epigenetic regulation by the molecular clock-sirtuin pathway

Joseph Bass

Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University

Clock proteins comprise an autonomous molecular network involved in organization and information processing from the genome to whole organisms across the lifespan. A central question remains how circadian transcriptional programs integrate physiologic systems in individual tissues and within the intact animal. A major step in understanding how the clock is coupled to metabolism originated with discovery that the clock produces rhythmic cycles of NAD+ turnover. Indeed, the observation that circadian mutant mice exhibit premature death and hypoglycemia when subjected to a prolonged fast, and that they develop both cardiomyopathy and skeletal myopathy, prompted us to examine the regulatory function of the clock-NAD+ pathway in mitochondrial metabolism. We have investigated the effect of NAD+ deficiency on mitochondria function in circadian mutant animals using a multi-faceted approach including unbiased proteomics leading to the identification of abnormal acetylation of enzymes involved in lipid oxidation, amino acid catabolism, tricarboxylic acid (TCA) cycle, electron transport chain (ETC), and superoxide dismutase pathways. Importantly, loss-of- function mutations in several of these oxidative enzymes have also been identified in the human metabolic myopathy syndrome and in both glioblastoma and renal cell carcinoma, indicating a broader effect of the clock-NAD+ pathway on mitochondrial metabolism in both normal and transformed cells. Using tissue- and cell-based bioenergetics assays, we found that abrogation of the clock impairs electron transfer from lipid to the TCA cycle, in addition to increased mitochondrial-production of superoxide free radical, increasing sensitivity to genotoxic tress. Our work also showed that cells exhibit an autonomous rhythm of oxygen consumption, glucose oxidation, and mitochondrial lipid catabolism. Importantly, the oxygen consumption cycle in muscle is directly linked to metabolism of NAD+ and activity of the mitochondrial NAD+-dependent deacetylase SIRT3. NAD+ supplementation using the pro-drug NMN influences both mitochondrial and transcriptional processes and improves respiration in live animals. Collectively, our studies indicate that circadian control of NAD+ metabolism and sirtuin function plays a key role in cellular respiration and aging.

65 How the brain generates REM sleep

Yu Hayashi1,2

1International Institute for Integrative Sleep Medicine, University of Tsukuba 2PRESTO, Japan Science and Technology Agency

Sleep in mammals has evolved into a complex phenomenon composed of two distinct states, REM (rapid eye movement) sleep and slow wave sleep. REM sleep is the major source of dreams, whereas slow wave sleep is characterized by a synchronous brain activity called slow waves. Both sleep states are unique to certain vertebrate species including human. Little is known, however, about the evolutionary origin or significance of these two states. Furthermore, the identity of the neurons responsible for generation of the two states is controversial due to the heterogeneity and complexity of the brainstem. Here, using the latest mouse genetic techniques, we identified neurons that robustly regulate transitions between REM and slow wave sleep. Furthermore, we show that these neurons share a common developmental origin with neurons that promote arousal. These results provide critical evidence about the neural mechanism of REM and slow wave sleep, and may also provide important information about the evolutionary origin of these sleep states.

66 Narcolepsy and genetic predisposition

Emmanuel Mignot, MD, PhD

Department of Psychiatry, School of Medicine, Stanford University

Narcolepsy is a neurological disorder characterized by excessive daytime sleepiness, cataplexy, hypnagonic hallucinations, sleep paralysis, and disturbed nocturnal sleep patterns. Narcolepsy is caused by the loss of hypocretin (orexin)-producing neurons in the lateral hypothalamus. Evidence, such as a strong association with HLA DQB1*06:02, strongly suggests an autoimmune basis targeting hypocretin neurons. Genome-wide association studies have strengthened the association between narcolepsy and immune system gene polymorphisms, including the identification of polymorphisms in the T cell receptor alpha locus, TNFSF4 (also called OX40L), Cathepsin H (CTSH) the purinergic receptor P2RY11, and the DNA methyltransferase DNMT1. Recently, attention has been raised regarding a spike in cases of childhood narcolepsy in 2010 following the 2009 H1N1 pandemic (pH1N1) in China and vaccination with Pandemrix, an adjuvanted H1N1 vaccine that was used in Europe. How the immune system may be involved in disease initiation and/or progression remains a challenge to researchers. Potential immunological pathways that could lead to the specific elimination of hypocretin producing neurons include molecular mimicry or bystander activation, and are likely a combination of genetic and environmental factors, such as upper airway infections.

67 A Conserved bicycle model for circadian clock control of membrane excitability

Ravi Allada

Department of Neurobiology, Northwestern University, USA

Clock control of membrane excitability is a property of master circadian pacemaker neurons that drive rhythms of sleep and wake. Yet the mechanisms underlying rhythms and the extent of their conservation remain unclear. Using patch clamp analysis in Drosophila DN1 clock neurons, we find that oscillation in resting sodium currents in the morning and potassium currents in the evening underlie rhythms of resting membrane potential. Using RNA-seq from DN1 neurons, we identified a novel molecular pathway linking the circadian clock to ion channel localization to control membrane excitability. Remarkably in mouse clock neurons, we find that sodium leak currents also oscillate with a peak during the day in opposite phase to resting potassium currents. Thus, alternating resting sodium and potassium currents act as a conserved “bicycle” mechanism for driving oscillations in membrane excitability in master clock neurons, suggesting an evolutionarily ancient origin to the neural mechanisms governing daily sleep and wake behavior.

68 Genetic and biochemical characterization of mammalian cilia compartmentalization

Pleasantine Mill

MRC Human Genetics Unit, Institute for Genetics and Molecular Medicine, Edinburgh, UK

Patterning of the embryo is a tightly controlled process which requires the correct integration and interpretation of key developmental signals. A cell makes a decision of whether to differentiate, divide or migrate in response to these environmental cues. Small microtubule-based projections, or cilia, found on almost every mammalian cell play a critical role in signal transduction during development and disease. This is because cilia have a unique composition that is enriched in many receptors and signalling components, analogous to an antenna for focusing signalling responses. Dysfunction of the cilium underlies a group of human genetic disorders, termed ciliopathies. The inability to maintain a cilium results in a spectrum of health problems ranging from skeletal defects and cystic kidney disease, to cognitive and behavioral defects, as well as obesity. Despite a growing list of genes implicated in cilia biology, we have very little idea what the encoded proteins actually do in cells, or how mutations cause the disease. Consequently most of these cilia-related diseases are currently untreatable. Using mouse as a genetic model of human disease, we aim to understand how cilia are maintained as a specialized signalling compartments. We are also searching for cell- type specific differences how traffic to the cilia, necessary for ciliary function, is regulated. Work from our studies on pan-ciliary retrograde IFT mutants as well as factors restricted to subset of cilia which are motile will be presented. Identifying novel ciliary components and characterizing their functions will lead to a better understanding for the diagnosis and clinical management within ciliopathy spectrum.

69 Strange and simple placozoans- ‘biologically immortal’ animals?

Hiroaki Nakano

Shimoda Marine Research Center, Faculty of Life and Environmental Sciences,University of Tsukuba

Placozoans are flat amoeba-like marine animals about 1mm, made up of only seven cell types arranged in three layers. They lack neurons and muscle cells, but are not sessile or parasitic, making them the simplest extant free-living animals. Placozoa is one of the four extant animal phyla not included within the Bilateria, together with the Ctenophora, Porifera, and Cnidaria. Their simple morphology and phylogenetic position make them important animals for uncovering the origins and early radiation of multicellular animals. However, due to their small size and lack of easily distinguishable traits, they are extremely difficult to find in the natural environment, and research on the animal is not as active as the other non-bilaterian phyla. In 1969, Karl G. Grell caught a single placozoan specimen from the Red Sea, the first report of the animal from a wild environment. During the next 45 years, this single animal has multiplied into millions of specimens, through several forms of vegetative reproduction such as fission and budding. Now, this laboratory-cultured strain, known as the Grell strain, is being studied in a number of laboratories worldwide. However, sexual reproduction has not been observed in the Grell strain. In fact, the developmental process, from embryos to adults, has not been reported for the phylum Placozoa. This implies that placozoans apparently possess limitless vegetative reproductive capacity and can be considered ‘biologically immortal’. Although placozoans may hide secrets for overcoming aging, there are few research on their longevity. I have succeeded in collecting placozoans in multiple locations around Japan (Nakano H., Sci. Rep. 4: 5356, 2014). We are aiming to establish experimental systems for the Japanese placozoans, and studies on these populations other than the Grell strain may be useful to uncover important biological mysteries that still remain unsolved for the phylum, including development and aging.

70 Mechanisms of haematopoietic stem cell development in mouse and human

A. Medvinsky, S. Rybtsov, A. Ivanovs, A. Batsivari

University of Edinburgh

Definitive hematopoietic stem cells (dHSC) develop in the AGM region in a step-wise manner. Using ex vivo modelling of HSC development in the mouse we have identified three types of precursors sequentially developing into dHSCs. Pro-HSCs are found in E9.5 embryos and are characterized by lack of CD43 expression, which is upregulated at later stages. Pre- HSCs Type I express CD41 but lack CD45 expression, which is subsequently upregulated in pre-HSCs Type II prior to their maturation into definitive HSCs. We show that SCF, but not IL3, is a major effector of HSC maturation during E9-10. In the mouse, the first HSCs emerge in the AoV. Here, we demonstrate that in the human embryo the first definitive HSCs also emerge asymmetrically and are localized to the AoV, which thus identifies a functional niche for developing human HSCs. Using magnetic cell separation and xenotransplantations, we show that the first human HSCs are CD34+VE- cadherin+CD45+C-KIT+THY-1+Endoglin+RUNX1+CD38-/loCD45RA-. This population harbors practically all committed hematopoietic progenitors and is under-represented in the dorsal domain of the Ao (AoD) and urogenital ridges (UGRs). The present study provides a foundation for analysis of molecular mechanisms underpinning embryonic specification of human HSCs. In conclusion, we present the hierarchical organization of the developing HSC lineage as a differentially regulated 4-step process and demonstrate that developmental progression of HSCs during a very short period of time is regulated by precise stage-specific molecular mechanisms. We also show some similarities and differences between mouse and human haematopoietic development.

71 TGF-β receptor signaling in breast cancer cell invasion and metastasis

Peter ten Dijke

Dept. Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands

The transforming growth factor-β (TGF-β) signalling pathway plays a critical and dual role in the progression of human cancer. During the early phase of tumour progression, TGF-β acts as a tumour suppressor, exemplified by deletions or mutations in the core components of the TGF-β signalling pathway. On the contrary, TGF-β also promotes processes that support tumour progression such as tumour cell invasion, dissemination, and immune evasion. Consequently, the functional outcome of the TGF-β response is strongly context-dependent including cell, tissue, and cancer type. In my talk, I will describe the molecular signalling pathways employed by TGF-β in cancer and how these, when perturbed, may lead to the development of breast cancer. Current TGF-β signalling inhibitors that are being evaluated in clinical trials for treatment of cancer patients target TGF-β or TGF-β receptors. These therapeutic agents are used systemically, and inhibit all TGF-β responses (bad and good). Therefore, while effective in inhibiting metastasis, they have a high chance of unwanted on- target side effects. With the aim to specifically target the oncogenic arm of the TGF-β and to leave the tumor suppressor arm intact, we have performed gain and loss of function genetic screens, combined with expression profiling studies of breast cancer tissues, to identify novel druggable regulators of pro-oncogenic TGF- β pathways in breast cancer. I will provide an update on our results on key signalling molecules that regulate the stability of specific TGF-β signaling components and thereby promote the TGF-β-induced breast cancer invasion and metastasis.

72 The role of the thymus in modulating γδ T cell suppressor activity during experimental Trypanosoma cruzi infection

Fabíola Cardillo1, José Mengel1 and Auro Nomizo2

1Oswaldo Cruz Foundation, Gonçalo Moniz Research Center (FIOCRUZ-CPGM), Rua Waldemar Falcão 121, 40295–001, Brotas, Salvador, Brazil 2Department of Clinical Analysis, Toxicology and Bromatology, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo (FCFRP-USP), Ribeirão Preto, Brazil

We have previously shown that splenic γδ T cells from young but not aged BALB/c mice possess suppressor activity in vivo and in vitro during the acute phase of Trypanosoma cruzi infection. The present work was undertaken to investigate the suppressor activity of γδ T cells from T. cruzi infected euthymic or athymic mice and the role of the thymus in modulating non- adherent spleen cell suppressor activity during the acute phase of infection. Splenic γδ T cells from aged or athymic BALB/c mice reconstituted with total spleen cells or non-reconstituted did not exhibit suppressor activity when added to full allogeneic, mixed lymphocyte cultures. In contrast, splenic γδ T cells from young euthymic BALB/c mice showed suppressor activity in vitro. Thymectomy reduced the splenic γδ T cell suppressor activity of young BALB/c mice in a time-dependent manner, following a T. cruzi challenge. The continuous provision of thymocytes to aged mice, young thymectomized mice or total spleen cell-reconstituted athymic mice could re-establish the γδ T cell suppressor activity. Of particular significance was the observation that the depletion of γδ T cells during the acute phase of T. cruzi infection restored the capacity of these mice to mount a humoral immune response to a non-related antigen such as ovalbumin. These results indicate that gd T cells of extrathymic origin cannot mediate suppression and that the thymus has a role in the regulation of suppression during the acute phase of T. cruzi infection.

73 Regulation of cancer stem cell potential by HMGA2, a chromatin regulator of epithelial-mesenchymal transition and biological aging

Kaoru Kahata1, E-Jean Tan1, Laia Caja2, Kalliopi Tzavlaki2 and Aristidis Moustakas1,2

1Ludwig Institute for Cancer Research and 2Department of Medical Biochemistry and Microbiology, Uppsala University, BioMedical Center, Sweden

Epithelial-mesenchymal transition (EMT) contributes to tumor cell invasiveness and the generation of cancer stem cells. Our laboratory aims at deciphering molecular mechanisms that link EMT to the generation and maintenance of cancer stem cells. We study the nuclear protein high mobility group A2 (HMGA2) that is required for the induction of EMT by transforming growth factor β (TGFβ) (Thuault et al. J. Cell Biol. 174:175-83, 2006). HMGA2 regulates a cohort of transcriptional regulators of the EMT process, such as Snail1 and Twist1 (Thuault et al. J. Biol. Chem. 283:33437-46, 2008; Tan et al. J. Biol. Chem. 287:7134-45). HMGA2 is an embryonic chromatin factor that is gradually and steadily downregulated during adult life with the exception of tissue stem cells, where its downregulation is induced by the aging process. Signal transduction by TGFβ and its related polypeptides, bone morphogenetic proteins (BMPs), coordinates physiological responses in diverse cell types. TGFβ promotes EMT, tumor cell invasiveness and metastasis, while BMP promotes mesenchymal-epithelial transition (MET) and suppresses tumorigenicity. The work that we will present focuses on the role of HMGA2 in breast carcinoma cell invasion and stem cell survival. Breast cancer cells that express high or lower levels of HMGA2 present a corresponding degree of self-renewal based on mammosphere assays. When HMGA2 is silenced from aggressive breast cancer cells, the phenotype shifts to an epithelial, indicative of MET, and concomitantly, tumor cells lose their self-renewing capacity. Transcriptomic analysis identified genes that are regulated by HMGA2 and which functionally link to the processing of miRNA biogenesis. Finally, by focusing on non-epithelial cancer stem cells, namely glioblastoma, we demonstrate that the ability of BMP to suppress glioma cancer stem cell self-renewal and tumorigenic potential depends on the transcriptional induction of Snail1, which induces differentiation of glioma cells and promotes a dramatic invasion of these cells within the recipient brain, while depleting the tumorigenicity from the same cells. Our work starts explaining in molecular detail how embryonic nuclear factors like HMGA2 and Snail1, when reactivated in human cancer, provide coordinated control of multiple genes, thus, promoting both the mesenchymal transition and tumor cell invasiveness, while, depending on the cell type of origin, they either promote or suppress cancer stem cell self-renewal.

74 Telomerase activation in yeast and cancer cells

Shu-Chun Teng

Department of Microbiology, College of Medicine, National Taiwan University

Telomeres are dynamic DNA-protein complexes that protect the ends of linear chromo- somes. Most telomeric DNA is synthesized by the enzyme telomerase. While most somatic cells do not express telomerase and therefore have limited life span, cancer cells can bypass the crisis either through telomerase reactivation or through an alternative recombination pathway for telomere lengthening (ALT). We will discuss our recent findings of telomere replication on telomerase expression, telomerase activation, and ALT progression. We demonstrated that telomerase is mainly activated by Cdk1/Tel1/Mec1 on telomeric binding protein Cdc13 from late S to G2 phase of the cell cycle. Hypernegatively charged do- main of Cdc13 contributed by Cdk1, Tel1 and Mec1 may provide an optimal interface to recruit the potential positively charged domain near the amino acid 444 lysine residue of Est1 in the telomerase complex. PP2A phosphatase and Aurora kinase coordinately inhibit the function of telomerase. Differential and additive actions of PP2A phosphatase and Aurora kinase on Cdc13 limit telomerase action by removing active telomerase from telomeres at G2/M phase. Moreover, previous studies have indicated that yeast Sgs1 and Top3 may work together to remove highly negative supercoils that are generated from telomere recombination. How- ever, the mechanism by which cells eradicate highly positive supercoils during recombination remains unclear. We demonstrate that Top2 is involved in telomere-telomere recombination, perhaps by resolving the highly positive supercoil structure at the front of the helicase. Inhibi- tion of topoisomerase II may be a promising therapeutic approach that can be used to prevent cell proliferation in ALT-type cancer cells.

75 Steroid hormones and aging: Lesson from the fruit fly Drosophila melanogaster

Ryusuke Niwa1,2, Chikana Yamamoto3 and Tomotsune Ameku4

1Faculty of Life and Environmental Sciences, University of Tsukuba 2PRESTO, JST 3College of Biological Sciences, University of Tsukuba 4Graduate School of Life and Environmental Sciences, University of Tsukuba

Steroid hormones are small lipophilic chemical compounds that mediate a wide variety of developmental and physiological events in almost all multicellular organisms. Recent studies suggest that steroid hormones are also involved in regulating animal aging (Antebi, Exp. Gerontol. 48: 596-602, 2013), whereas detailed mechanism of steroid hormone-dependent aging control is still unclear. To investigate a role of steroid hormone in animal aging, we have been using the fruit fly Drosophila melanogaster as a model organism. In insects, the principal steroid hormones are ecdysteroids, which are synthesized from dietary cholesterol via multiple conversion steps. In the last decade, we have identified ecdysteroidogenic enzymes and developed genetic tools to knock-down these genes in vivo (Niwa and Niwa, Genes Genet. Syst. 89: 27-34, 2014; Niwa and Niwa, Biosci. Biotechnol. Biochem. in press, 2014). Utilizing these tools, we succeeded in creating tissue-specific loss-of-function animals of ecdysteroidogenic enzyme genes and examining aging phenotype. In this presentation, we will present our most recent data and discuss an effect of ecdysteroids on aging.

76 Long live the queen – the molecular and endocrine underpinnings of the reproduction/lifespan paradox in social insects

Klaus Hartfelder

Department of Cell and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo

A tradeoff between reproductive output and lifespan is a basic rule in all major metazoan clades, especially in the female sex, and the primary underlying mechanisms are the insulin/ insulin-like signaling (IIS) and TOR pathways. Though apparently tight, this tradeoff relationship is broken in social insects, with their highly reproductive, long-lived queens and sterile, short-lived workers. Two points need to be addressed to understand this dissociation: the endocrine and genomic responses to the environmental stimuli driving caste development, and the factors underlying the flexibility in caste lifespan. The primary switch between queen and worker development is the feeding regime of the larvae with royal jelly. This affects the larval endocrine system, with queen larvae producing large amounts of juvenile hormone, a potent stimulator of queen development. Other signaling systems investigated more recently through gene expression and functional analyses are the IIS, TOR and Egfr pathways. Interestingly, the expression patterns of insulin receptor, TOR and Egfr encoding genes all differed from expectation, as all were less expressed in queen than in worker larvae. Underlying this apparent paradox seems to be an endogenous hypoxia response in the worker caste. The primary organ affected by all these developmental signals is the larval ovary, which, in workers, is subject to massive autophagic cell death, thus severely restricting the adult reproductive potential. In the adult honeybees, the queen fat body produces large amounts of vitellogenin, which sustains their enormous egg laying rates. But different form other insects, vitellogenin synthesis is independent of juvenile hormone. Rather, this hormone has taken on a repressor role for vitellogenin production in the worker caste, and this negative feedback relationship between vitellogenin and juvenile hormone is thought to be the major lifespan determinant. Such rewiring of ancestral signaling pathways makes honeybees a model system for eco-evo-devo studies on aging and reproduction.

77 Nutrient-dependent regulation of steroid hormone biosynthesis in the puberty of fruit fly Drosophila melanogaster

Yuko Shimada-Niwa1 and Ryusuke Niwa1,2

1Faculty of Life and Environmental Sciences, University of Tsukuba 2PRESTO, JST

Steroid hormones play crucial roles in many aspects of development, growth, reproduction and aging. They have a conserved role in controlling the developmental transition from juvenile to adult across animal phyla. For example, human steroid hormones promote the development of secondary sexual characteristics at puberty, leading to adult sex maturation. The steroid hormone ecdysteroid determines the timing of molting and metamorphosis. Interestingly, the temporal coordination of steroid hormone biosynthesis during the juvenile- to-adult transition is tightly coupled to nutrient conditions in the juvenile stage, which allows organisms to increase their survival fitness and reproductive success. However, it remains unclear how nutrient information is reflected to control of the timing of steroid hormone biosynthesis. The fruit flyDrosophila melanogaster provides a suitable model for studying the regulatory system of steroid hormone/ecdysteroid biosynthesis (Niwa and Niwa, Biosci. Biotechnol. Biochem. in press, 2014). During the larval stages, a form of ecdysteroid, ecdysone is synthesized in a special endocrine organ called the prothoracic gland (PG). Several ecdysteroidogenic enzymes mediate the conversion steps from cholesterol to ecdysone in the PG. Therefore, one of the fundamental questions is how the PG cells sense nutrient condition and then transduce the signal to ecdysone biosynthetic pathway (Niwa and Niwa, Genes Genet. Syst. 89: 27-34, 2014). To address this question, we focus on a subset of serotonin (5-hydroxytryptamine, 5-HT)-producing neurons that directly innervate the PG. These neurons share their tracts with enteric nervous system and are responsive to nutrient condition. Our result suggests that 3 pairs of serotonergic neurons are responsible for the timing in the transition of growth (the larval stage) to maturation (the pupal stage). Moreover, serotonin signaling in the PG is involved in the timing of ecdysteroid biosynthesis. Based on these results, we propose that serotonergic neuronal control mediates the nutrient-dependent developmental plasticity via modulating steroid hormone biosynthesis in the juvenile-to-adult transition.

78 Impact of n-3 polyunsaturated fatty acid deficiency on mesoaccumbens dopaminergic transmission and motivation: relevance for the negative symptoms of schizophrenia

Pierre Trifilieff1,2

1Nutrition and Integrative Neurobiology, INRA UMR 1286, Bordeaux, France 2University of Bordeaux, France

Brain function is known to depend on genetic as well as environmental factors. Accumulating evidence suggests that nutrition can be a main environmental factor that influences both brain development and function and thereby participate to the etiology of various psychiatric disorders. In particular, schizophrenia has been associated with a deficiency in n-3 polyunsaturated fatty acid (PUFA) in the brain, however, the mechanisms by which n-3 PUFA deficiency could participate to the etiology of schizophrenia are unknown. In this presentation, I will emphasize how both human and animal studies have shed light on the implication of mesolimbic dopamine transmission in various symptoms of schizophrenia. I will then present recent data showing that n-3 PUFA deficiency leads to neurobiological and behavioral phenotypes that resemble those described in schizophrenia. In particular, our results indicate that developmental n-3 PUFA deprivation leads to a selective decrease in motivation in adulthood, a main negative symptom of schizophrenia. This behavioral impairment was accompanied by an increase in both dopamine D2 receptor expression and extracellular dopamine levels in the nucleus accumbens a main region involved in the modulation of motivation. Importantly, these effects were not reversed by n-3 PUFA supplementation at weaning. These data show for the first time that developmental n-3 PUFA deficiency leads to alteration of dopaminergic transmission and motivation deficit in adulthood, and could thereby constitute a main environmental factor for the development of motivation deficits as well as certain psychiatric disorders such as schizophrenia.

79 Δ9-THC restores age-related changes in the brain

A. Bilkei-Gorzo1, O. Albayram1, A. Piyanova1, M. Dvir-Ginzberg3, A. Draffehn2, I.Bab3, J. Schultze2, I. Rácz1, S. Imbeault1, A. Zimmer1

1Institute of Molecular Psychiatry, University of Bonn; 2Genomics and Immunoregulation, LIMES Institute, University of Bonn; 3Institute of Dental Sciences, The Hebrew University Jerusalem

Aging of the brain is accompanied by a progressive decline in cognitive abilities associated with reduced synaptic densities. This process is accelerated in mice lacking cannabinoid CB1 receptors. We have therefore wondered if an increase of the cannabinoid tone in older animals would protect them against the loss of cognitive functions. Two age groups of animals were therefore treated with 3 mg/kg/day Delta-9THC for 28 days through osmotic minipumps. This treatment significantly improved spatial learning in the Morris water maze test as well as object location recognition in the old but not in the young mice. The improved cognitive performance was associated with increased synaptic densities and enhanced expression of synaptic marker proteins. We next investigated the gene expression profile of control and THC treated young and old mice. We found that THC treatment altered the expression of a number of age-related genes in the old but not in the young mice. The CREB and Erk signaling systems were activated in THC treated old animals shown by an enhanced phosphorylation. The beneficial effects of THC on brain ageing was mediated by CB1 receptors, because THC treated CB1 knockout mice failed to show any improvement in learning ability, increase in synaptic densities or change in gene expression.

80 Effects of acute stress on memory processes

J. Micheau, C. Huguet, P. Faucher, J. David & N. Mons

University of Bordeaux, CNRS UMR 5287, INCIA, Talence, France

Although the effects of acute stress on learning abilities have been investigated since decades data from the literature are still very confusing. The concomitant release of noradrenaline and corticosterone in response to stressful situation has been demonstrated to modulate positively or negatively learning and memory processes according to many variables such as stress intensity, the emotional valence of the learned material or the interval between stressful episode and learning experience. In this report we have investigated in mice, the importance of the timing of the application of the stressful event (acute restraint stress (ARS): 50mn) on consolidation and encoding processes. In a first series of experiments the impact of ARS was assessed on the consolidation of contextual fear memory which is supposed to depend on hippocampal function. We showed that when conditioning was performed 5mn or 6h after completion of ARS long-term retention of contextual fear memory was impaired whereas short-term memory was spared. We then, analysed the behavioural and molecular (ERK1/2- CREB pathway) impact of the modulation of corticosterone status after either systemic or intra-hippocampal treatments. In a second series of experiments, we have investigated the importance of the inter-stress training interval (5mn and 6h) on online information processing by using an episodic-like memory task, namely object recognition. Compared to non-stressed mice ARS had a facilitating or an impairing influence on object recognition during testing when completed 6h or 5mn before the task respectively. Taken together, our results suggest that, in addition to direct corticosterone influence a tentative explanation of stress effects on memory processes must consider delayed molecular and cellular mechanisms, including genomic activation. Finally, we integrate our data in a functional model of how stress might affect memory processes in which amygdalar modulation of hippocampal function via noradrenaline input is also incorporated.

81 Midbrain dopamine neurons are divided into anatomical subgroups encoding distinct signals

Masayuki Matsumoto

Laboratory of Cognitive and Behavioral Neuroscience, Faculty of Medicine, University of Tsukuba

Dopamine neurons in the substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA) have been shown to encode a reward value signal and to play important roles in reinforcement and motivation. Our recent study reported, however, that not all dopamine neurons encode the value-related signal uniformly. Using a classical conditioning with appetitive and aversive outcomes (liquid rewards and aversive airpuffs) in monkeys, we found that some dopamine neurons were excited by reward-predicting stimuli and inhibited by airpuff-predicting stimuli, as the value-coding theory predicts. However, a greater number of dopamine neurons were excited by both of these stimuli, inconsistent with the theory. These data led a hypothesis that dopamine neurons are divided into multiple populations encoding distinct signals. Consistent with this idea, the dopamine system has been reported to be involved in a number of functions, not only in motivational functions but also in some cognitive ones. However, despite abundant studies demonstrating dopamine neuron activity related to reward, little is known about what signals dopamine neurons convey to promote cognitive processing. Therefore, we next examined dopamine neuron activity in monkeys performing a delayed matching-to-sample task that required working memory and visual search. We found that dopamine neurons responded to task events associated with cognitive operations. A subset of dopamine neurons were excited by visual stimuli if the monkey had to store the stimuli in working memory. These neurons were located dorsolaterally in the SNc, whereas ventromedially located dopamine neurons, some in the VTA, represented a reward value signal. Furthermore, dopamine neurons monitored visual search performance, becoming active when the monkey made an internal judgment that the search was successfully completed. Our findings suggest that dopamine neurons are divided into anatomical groups suitable for distinct functions.

82 Imaging of iatrogenic dysimmunity

Vincent Dousset1,2 and Thomas Tourdias1,2

1Laboratory Physiopathology of Neuronal Plasticity U INSERM 862 University of Bordeaux 2Departement of NeuroImaging University Hospital of Bordeaux

With the increasing use of monoclonal antibodies to treat patients with several central nervous system (CNS) diseases, adverse events related to medication-induced immunity are developing. In Multiple Sclerosis, a frequent disease that destroys the myelin and neurons of young adults, the use of Tysabri® (Natalizumab), a monoclonal antibody directed against VLA4 lymphocytes receptors has shown to be very efficient. However, due to restriction of lymphocytes trafficking through the CNS, the immune defense against infectious diseases is decreased. An ubiquitous virus, JC virus, might developed in about 1 to 3% of treated patients. JC virus has a strong pathogenicity to the oligodendrocyte a CNS that provides myelin sheath making a superimposed disease called progressive multifocal leukoencephalopathy (PML). Early recognition of Natalizumab-induced PML by magnetic resonance imaging (MRI) is a key factor to reduce the risk for spreading PML that might lead to patient death, occurring so far to ¼ of affected patients. In addition, MS patients were also shown to develop a strong brain immune reactivity called immune restoration inflammatory syndrome (IRIS) after stop- ping monoclonal antibodies treatment. In Alzheimer disease (AD), use of monoclonal antibodies to remove amyloid protein or tau proteins from the brain, is still under promising investigations. However, during the treatment auto-immune reactivity of the CNS has been described in patients, leading to brain parenchyma or meninges edema or hemorrhages. MRI plays an important role to an early recognition of such adverse effects that might be clinically silent at the early stage. Later, strong hemorrhage or cortical abnormalities might lead to patient clinical worsening.

83 Activation of microglia impacts their directional motility

Elena Avignone1,2

1Univ. Bordeaux, Institut Interdisciplinaire de Neurosciences, UMR 5297, F-33000 Bordeaux, France 2CNRS, Institut Interdisciplinaire de Neurosciences, UMR 5297, F-33000 Bordeaux, France

Microglia cells are the resident macrophages of the central nervous system and are con- sidered its first line of defense. They are highly motile cells. During physiological conditions they constantly move their tiny processes in an apparently random way (basal motility) to scan the parenchyma, and in few minutes they can extend their processes towards a site of injury or substances that represent a dangerous signal (directional motility). In pathological conditions, microglia become activated. Activation is a multifaceted pro- cess, which may last several days and can become chronic. It depends on the stimulatory context, and it plays a critical role in all neuropathologies associated with an inflammatory reaction, including epilepsy. How activation affects microglial ability to scan the brain or to respond to noxious stimuli is still an open question. In a previous work (Avignone et al. J. Neurosci. 2008), we show that in the model of kainate induced status epilepticus (SE) microglial processes moved faster towards a pipette containing an ATP analogue (2MeADP), suggesting that activation may affect directional motility. In this work we investigated the effect SE induced activation on basal motility and two types of directional motility: in response to acute laser lesions and to local application of 2MeADP. To characterize the morphological dynamics of microglia we used time-lapse two-photon imag- ing in acute hippocampal slices from transgenically labeled mice (CX3XR1+/EGFP). The effect of activation was strikingly different on different types of motility. It increased the scanned territory of single processes during basal motility while, despite it increases the velocity towards a 2MeADP containing pipette, it did not affect the directional motility to- wards an acute laser induced lesion. In summary activation induced by a status epilepticus did not hamper the sentinel role of microglia, and the heterogeneity of the effect of activation on different types of motility strongly suggests that motility should be considered as stimulus dependent.

84 Post-translatinal modification by small ubiquitin-modifier SUMO in the cell biology of Giardia lamblia

Renata R. Tonelli

Departamento de Ciências Biológicas, Universidade Federal de São Paulo, Diadema, Brazil

Posttranslational modifications of proteins play critical roles in the control of cellular differentiation, development, and environmental adaptation. In particular, the covalent attachment of the Small Ubiquitin-like Modifier (SUMO) to target proteins (sumoylation) regulates cell cycle progression, transcription, nucleocytoplasmic transport, and stress responses. The SUMO conjugation pathway is biochemically similar to ubiquitin conjugation, although the enzymes within the pathway act exclusively on SUMO proteins. Sumoylation, and enzymes of the sumoylation pathway, are conserved in the binucleated, flagellated parasite, Giardia lamblia. In this work the biological role of SUMO in Giardia is examined. G. lamblia (also called Giardia intestinalis) is one of the most common intestinal parasites of humans and has a worldwide distribution. Giardia possesses a unique SUMO orthologue (Gl-SUMO) that shares 47% sequence identity with mammalian SUMO-1 and 17% sequence identity with ubiquitin. Indirect fluorescence analysis using a monoclonal antibody against SUMO showed an extra-nuclear localization reacting with the median body, ventral disc, flagella tips and cytoplasm in trophozoites. In cysts, the anti-SUMO antibody reacted with the internalized flagella and some structures not identified, as yet. Treatment of trophozoites with ginkgolic acid (an inhibitor of the SUMOylation pathway) resulted in reduced amount of SUMO conjugates in a dose-dependent manner. Furthermore, treated parasites displayed a round-shaped morphology in contrast to control cells, which retained their characteristic pear-shaped structure. Finally, double confocal immunofluorescence with anti-SUMO and antibodies against modified tubulins confirmed that acetylated tubulins at the median body are SUMOylated. Further studies are warranted to investigate how SUMOylation of cytoskeleton proteins affects biological events in Giardia lamblia. (FAPESP #2010/15042-2).

85 Interaction of small viral capsids with the nuclear pore - they are no classical cargo

Michael Kann, Manvi Porwal, Kenza Snoussi, Ruth Popa-Wagner, Harald Wodrich, Christiane Dinsart, Jürgen A. Kleinschmidt, Nelly Panté, André Schmitz

Microbiologie fondamentale et Pathogénicité, CNRS - Université Bordeaux, France; Institute for Medical Virology, Giessen University, Germany; ATV, DKFZ Heidelberg, Germany; Institute of Zoology, UBC,Vancouver, Canada

Macromolecules enter the nucleus by active transport through the nuclear pore complex (NPC). Translocation is mediated by nuclear transport receptors interacting on one hand with the cargo and on the other hand with the proteins of the NPC, which are collectively called nucleoporins (Nups). Within the nuclear basket, which is a cage-like structure formed by eight filaments on the nuclear side of the NPC, the import complex is dissociated leading to release of the cargo and its diffusion deeper into the karyoplasm. DNA viruses have high jacked this transport mechanism in order to translocate their genome to the site of genome multiplica- tion. Practically all viruses (or viral capsids) have however diameters exceeding the maximal transport diameter of the NPC, which is 39 nm, and they release their genome complexed by karyophilic viral proteins prior to genome translocation into the karyoplasm. Hepatitis B virus (HBV) and parvoviruses (PV) are DNA viruses with capsids below the maximal NPC trans- port limit. Theoretically they thus allow that their genomes enter the karyoplasm in an intact capsid as a karyophilic cargo followed by nuclear genome release. Analyzing the interactions of both viral capsids with the nucleus we observed however entirely different strategies: HBV capsids pass the nuclear pore and enter the nuclear basket intact where they interact specifi- cally with one protein in the basket. This interaction causes arrest of the capsid in the basket, which is followed by capsid dissociation and genome release. PV also interact with Nups but instead of being arrested they activate enzymes involved in mitosis. This activation causes local, transient nuclear envelope break-down allowing that larger structures as a viral capsid pass.

86 Novel ‘in situ’ preparation of zinc finger nucleases based on Ni(II)-induced specific hydrolysis of proteins

Brigitta Csipak1, Agnieszka Belczyk2, Masamitsu Asaka3, Kyosuke Nagata3, Wojciech Bal2, Béla Gyurcsik1

1Department of Inorganic and Analytical Chemistry, MTA-SzTE Bioinorganic Chemistry Research Group, University of Szeged, Hungary 2Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Poland 3Nagata Special Laboratory, Faculty of Medicine, University of Tsukuba, Japan

Zinc-finger proteins recognize specific DNA sequences. With such modular proteins a selected DNA sequence can be targeted by the proper design of the sequential finger units. In addition, fusion of zinc-finger domains to proteins with enzymatic function can be applied for manipulating DNA. Chimeric nucleases constructed from zinc-fingers and the nuclease do- main of FokI restriction endonuclease are useful tools of targeted cleavage of genomic DNA. Such agents can be applied in therapy of monogenetic diseases in the future (B. Gyurcsik and A. Czene, Future Med. Chem., 2011, 3, 1935–1966). Recently, it has been recognized that nickel(II)ions promote site specific hydrolysis of pep- tides or proteins at the X-(S/T)-Y-H-Z sequence, where the variable X,Y and Z amino acids in- fluence the reaction rate and efficiency (E. Kurowska, et al., Metallomics, 2011, 3, 1227–1231). The metal complex formed upon the cleavage of the protein is able to cleave DNA. Thus, an in- duced specific damage to DNA can be performed by applying a specific DNA binding protein. Based on the above considerations our research is focused on the design of novel artificial nucleases that are created ‘in situ’ by the site-specific hydrolysis of specific DNA binding pro- teins, such as, e.g. zinc-fingers. These proteins can be activated by the addition of nickel(II) ions, and as such, their action can be controlled by the concentration of this metal ion. We demonstrated the site-specific hydrolytic cleavage of a zinc-finger protein containing three metal ion binding site, by gel electrophoresis and by mass spectrometric identification of the HPLC separated cleavage products. In parallel, we have also applied a redesigned zinc-finger protein with only one cleavage site. An intriguing question to be answered is, whether the same reaction occurs in the presence of DNA and whether the DNA can be specifically cleaved by the newly formed protein complexes?

87 Real time analyses of the DNA damage response in mammalian cells

Xiangduo Kong1, Elizabeth Hinde2, Barbara Alcaraz Silva3, Michelle Digman2, Enrico Gratton2, Michael Berns3, and Kyoko Yokomori1

1Department of Biological Chemistry, School of Medicine, University of California, Irvine, USA, 2Laboratory for Fluorescence Dynamics, Department of Biomedical Engineering, University of California, Irvine, USA; 3Beckman Laser Institute and Medical Clinic, University of California, Irvine, USA

Genome integrity is continually threatened by endogenous metabolic products generated during normal cellular respiration, by errors that arise during DNA replication and recombination, and by exogenous exposure to DNA damaging agents. The resulting DNA lesions, if not faithfully repaired, can accumulate as mutations ranging from single nucleotide changes to chromosomal rearrangements and loss that can lead to cancer, developmental abnormalities, and cell death. Accumulation of DNA damage is also a hallmark of cellular senescence and aging. Different insults to DNA are recognized by lesion-specific repair factors, which invoke distinct repair pathways including base excision repair (BER) and double-strand break (DSB) repair. The factors most critical for DNA repair, as well as the major players in the DNA damage response (DDR), have been largely identified through genetics-based studies using model organisms or through investigation of human diseases. However, how their activities are coordinated in the cell nucleus is still not well understood, and we still do not have a complete picture of the cellular signaling and chromatin responses following DNA damage. We investigate the DDR in real time in living cells following site-specific DNA damage using fluorescent imaging techniques including fluorescence lifetime imaging microscopy and pair- correlation function (pCF) analyses. Our recent findings on damage signaling in the cell will be discussed.

88 Identification of disease-casing variants using next generation sequencing

Emiko Noguchi1,2, Kazumasa Kanemaru3, Satoko Tahara-Hanaoka2,3, Akira Shibuya2,3

1Department of Medical Genetics, Faculty of Medicine, University of Tsukuba 2Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency 3Department of Immunology, Faculty of Medicine, University of Tsukuba

Recent advances in next-generation sequencing (NGS) technologies allow the rapid identification of disease-causing mutations. We applied the NGS technologies to identify disease causing mutation in mice. Nc/Nga mouse is a inbred stain established from Japanese fancy mice by Kondo ( University, Nagoya, Japan) in 1957. NC/Nga mice spontaneously develop an eczematous atopic dermatitis-like skin lesion when kept under conventional condition. Mode of inheritance in Nc/Nga mouse was considered to be autosomal recessive. We performed exome sequence using DNA obtained from Nc/Nga mice on SOLiD5500xl sequencer (Life Technologies). We selected variants that satisfied all of the following (1) homozygous mutations, (2) not observed in other strains, (3) nonsense or frameshift mutations, resulting in 10 nonsense mutations and 41 frameshift mutations. Among them, 6 for nonsense and 23 for frameshift mutations were verified by Sanger sequence. Functional analysis of the candidate mutation identified in Nc/Nga mouse by exome sequence and application of NGS will be discussed.

89 Biocompatible antiradicals inspired by fluorescent flowers

Karina Kinuyo Nakashima, Nathana Barbosa Lopes, Letícia Christina Pires Gonçalves and Erick Leite Bastos

Departamento de Química Fundamental, Instituto de Química, Universidade de São Paulo

Betalains are water-soluble, chiral and nontoxic natural pigments, which have gained attention due to their high antioxidant capacity (Kanner J et al., J. Agric. Food Chem. 49: 5178-5185, 2001), applicability (Gonçalves LCP et al., Plos One 8: e53874, 2013; Gonçalves LCP et al., Plos One 8: e73701, 2013) and occurrence in fluorescent flowers (Gandia-Herrero F et al., Nature 437: 334-334, 2005). All betalains are biosynthesized from betalamic acid, an α,β-unsaturated aldehyde with high antiradical capacity (Gonçalves LCP et al. J. Food. Eng. 118: 49-55, 2013). The main pigment in the red beet, betanin (Bn, betanidin 5-O-β-glucoside), belongs to the class of betalains and has been used as a food colorant (E162, FDA) as well as a therapeutic agent. Very low concentrations of dietary betanin have been shown to inhibit skin and liver tumor formation in mice (Kapadia GJ et al., Pharmacol Res 47: 141-148, 2003) and to protect mice from the effects of γ-radiation (Lu, X et al., Eur. J. Pharmacol. 615: 223- 227, 2009). The high antiradical capacity of Bn has been demonstrated in both in vitro and in vivo tests and, although the presence of the cyclo-DOPA moiety may be fundamental for the high scavenging activity of Bn, the 1,7-diazaheptamethinic system has been assumed to play a major role in the antioxidant response (Butera D et al., J. Agric. Food Chem. 50: 6895- 6901, 2002). Our research group at the University of Sao Paulo (USP), Brazil, investigates natural fluorescent pigments to establish structure-property relationships and to create new functional chemicals. In this study, we investigate the mechanism of antioxidant action of betalains. Model phenolic betalains were semisynthesized using betalamic acid as starting material (which was obtained from renewable sources, such as the beetroot, the pitaya fruit, and flowers from plants of most families of the Caryophyllales order) and their antiradical capacity was studied by means of kinetic measurements, determination of isotope effects and DFT calculation of relevant physico-chemical parameters.

90 The Anthocyanins: plant pigments with multiple functions in nature

Frank H. Quina

Instituto de Química, Universidade de São Paulo, Brazil and NAP-PhotoTech-The USP Research Consortium for Photochemical Technology

The anthocyanins are natural, water-soluble plant pigments responsible for the majority of the red, blue and purple colors of flowers, fruits and leaves. In flowers, the colors imparted by anthocyanins serve primarily to attract pollinators. In fruits, anthocyanins attract herbivores responsible for seed dispersal and provide the fruit with antioxidant protection. In red and purple plant leaves, the primary function appears to be protection of the photosynthetic apparatus from excess solar radiation. The basic chromophore responsible for the color of anthocyanins is a 7-hydroxyflavylium cation, the color of which is determined by the type and number of other substituents that are attached to the chromophore, by the local pH and by complexation with metal cations or with colorless co-pigment molecules. At pH > 3, water adds to the colored cation form of anthocyanins to give a colorless hemiacetal, which can ring- open to give a cis-hydroxychalcone and subsequently isomerize to the trans-hydroxychalcone, both of which are colorless or pale yellow, resulting in essentially complete color loss at neutral pH. Our group is interested in understanding and predicting this rich, pH-dependent chemistry of anthocyanins and its implications for the photoprotective role and the anti-oxidant activity of anthocyanins. In addition, a deeper understanding of the mechanisms utilized by plants to maintain the color of anthocyanins at pH > 3 in vivo should aid in the development of new strategies for stabilizing the color of anthocyanins in vitro so that these natural plant pigments can be successfully employed in a wider range of practical applications.

91 Genome-wide remodeling of long-range interactions during skeletal muscle differentiation

Ricardo Ramirez1,2,*, Katherine Fisher3,*, Huay Mei Poh4,Santiago V Lombeyda5, Anthony G. Kirilusha3, Kenneth McCue3, Ana Conesa6, Yijun Ruan4, Barbara Wold3+, Ali Mortazavi1,2+

1Department of Developmental and Cell Biology, University of California, Irvine, CA, USA, 2Center for Complex Biological Systems, University of California, Irvine, CA, USA, 3Division of Biology, California Institute of Technology, Pasadena, California, USA 4The Jackson Laboratory for Genomic Medicine, and Department of Genetic and Development Biology, University of Connecticut, USA 5Center for Advanced Computing Research, California Institute of Technology, Pasadena, California, USA 6Genomics of Gene Expression Lab, Centro de Investigaciones Principe Felipe, Valencia, Spain *Authors contributed equally to this work +Corresponding authors

Eukaryotic developmental programs require the orchestration of both transcriptional regulatory mechanisms and chromatin architecture with acute spatial-temporal precision. We investigated the interactome of CRMs during mouse skeletal muscle cell (C2C12) differentiation by integratively analyzing DNase-seq with chromatin long-range interactions using RNA Polymerase II ChIA-PET. We identified a total 215,977 candidate CRMs genome- wide, of which ~50% were quantified to be differentially hypersensitive during differentiaton. DNaseI Footprinting analysis allowed us to identify transcription factor footprints and de novo motif enrichments of key Myogenic Regulatory Factors (MRF). We integrated CRM and DNaseI Footprinting information with ChIA-PET to generating high-resolution (1kb) and medium-resolution (3kb) Chromatin Interaction Graphs (CIG) during cellular commitment. We characterized a large number of interactions specific to each cell-type, with 6,567 found in undifferentiated C2C12, 16,426 specific to differentiated C2C12, and 9,881 interactions common to both. We quantified changes in DNaseI and gene expression activity across promoters genomewide and identified distinct classes of promoters with strongly correlated activity of DNaseI and gene expression, while explaining that uncorrelated behavior for a class of promoters is consistent with changes in long-range chromatin control. Our results demonstrate the power of integrating long-range interactions to understand the changes in gene expression during skeletal muscle differentiation.

92 Metabolomics and in silico tools in the search of natural compounds from plants with anti − inflammatory potential

Daniela A. Chagas-Paula1, Tiago B. Oliveira1, Tong Zhang2, RuAngeli Edrada − Ebel2 and Fernando B. Da Costa1

1University of São Paulo, School of Pharmaceutical Sciences of Ribeirão Preto, Ribeirão Preto, SP, Brazil 2Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, Scotland

The non − steroidal anti − inflammatory drugs are among the most common group of drugs used in the world. However, side effects still occur and some inflammatory pathologies lack efficient treatment. Cyclooxygenase (COX) and lipoxygenase (LOX) pathways are of great importance in inflammatory processes and therefore inhibitors for both of them are needed. Dual inhibitors on COX − 1 and 5 − LOX should be anti − inflammatory medicines with high efficacy and low side effects and therefore would be useful to treat acute as well chronic inflammatory processes, such as rheumatoid arthritis and asthma. Because the anti − inflammatory potential of Asteraceae plant species is well known world wide, several extracts were screened in vitro against the enzymes COX − 1 and 5 − LOX and analyzed using a non − targeted LC − MS − based metabolomics approach. Ethanol − water extracts were prepared using 2 mg of dried and powdered leaves. Among the 57 screened extracts, 13 of them displayed dual inhibition on COX − 1 and 5 − LOX. The extracts were further analyzed by LC − MS and their data were processed. The Dictionary of Natural Products and an in − house database were used for extract dereplication. The resulting 6,052 peaks of all extracts were combined with their biological activity data and selected by genetic algorithm affording 1,261 peaks. A model using decision trees was built and 11 compounds were determined as the biomarkers for the dual inhibition on COX − 1 and 5 − LOX. Finally, using the LC − MS data of the biomarkers and the anti − inflammatory results of selected extracts, a model to predict new anti − inflammatory extracts with no prior biological activity information was built using artificial neural networks. In summary, a new and robust approach for prediction of the activity of natural compounds against COX − 1 and 5 − LOX was developed. Moreover, this approach can be useful to predict the bioactivity of non − investigated extracts taking into account only their LC − MS data. Acknowledgements: CNPq, CAPES and FAPESP.

93 Design principles of biological growth control

Arthur D. Lander, M.D, Ph.D.

Center for Complex Biological Systems, and Departments of Developmental & Cell Biology and Biomedical Engineering, University of California, Irvine, CA, USA

Our bodies arise through a process of controlled growth that can exhibit remarkable speed and precision. That this can happen is quite amazing, given that the units of growth—cells and parts of cells—are self-reproducing, which means they increase by a process of exponential expansion. Exponential processes are naturally unstable (bombs and nuclear reactors are good examples) and tend to be very sensitive to external perturbations (because errors compound), making them among the most difficult processes to control. What general principles does nature use to tackle this problem? Engineers typically exploit feedback to achieve control, and many lines of evidence point to a critical role for molecular feedback in regulating biological growth. But although some specific molecules and mechanisms have been implicated, we still have a very limited understanding of what information is being fed back, and for what purpose. Often our understanding of what is not being fed back is greater: for example, there are many organs or tissues whose final sizes are known to be specified in a manner independent of body size, independent of cellular growth rate, independent of elapsed time, and independent of cell size. In my talk, I will discuss some insights into growth control strategies that have emerged from modeling and experiments focused on the regulated progression of cells through lineage stages. I will also discuss how the design principles behind these strategies may be generalized to other types of biological growth systems, and may even relate to problems of controlled growth in non-biological (e.g. social, economic) arenas.

94 NOTE

95 NOTE

96 The Second Research University Symposium – Leading-edge Researches and System/ Research-ethics to Support Trusted Ones – In conjunction with The Fourth Tsukuba URA Forum

(The program for promoting enhancement of research universities, Ministry of Education,Culture,Sports,Science and Technology)

Reserch Administration Office University of Tsukuba

97 Sep 28 (Sun) Hall The Second Research University Symposium - Leading-edge Researches and System/Research-ethics to Support Trusted Ones - in conjunction with The Fourth Tsukuba URA Forum

13:30-13:40 Yasuo Miake University of Tsukuba Introductory

Part I: Introduction of Leading-edge Researches in University of Tsukuba

13:40-14:20 Masashi Yanagisawa University of Tsukuba Solving the mystery of sleep

14:20-15:00 Hiroyuki Kusaka University of Tsukuba Computational sciences empowering heat island research

15:00-15:15 Break Part II: How to support "Trusted Researches"?

Design Division, Japan Patent Protection of intellectual property right - Focusing on design 15:15-15:45 Tokie Tani Office examination system -

15:45-16:15 Kaori Yamaguchi University of Tsukuba Coaching with integrity

16:15-16:45 Koji Okabayashi University of Tsukuba Research management and academic integrity

National Institute for Materials 16:45-17:15 Shinya Uji How can research be trusted? Science

17:15-17:45 Hajime Nagahara ASAHI KASEI CORPORATION An example; R&D management in industry

17:45 Tadashi Baba University of Tsukuba Closing

* The official language of the Symposium will be Japanese. * The abstracts are distributed in the separate booklet at the conference room.

98

5 / 26 ページ Sep 28 (Sun) Hall The Second Research University Symposium - Leading-edge Researches and System/Research-ethics to Support Trusted Ones - in conjunction with The Fourth Tsukuba URA Forum

13:30-13:40 Yasuo Miake University of Tsukuba Introductory

Part I: Introduction of Leading-edge Researches in University of Tsukuba

13:40-14:20 Masashi Yanagisawa University of Tsukuba Solving the mystery of sleep

14:20-15:00 Hiroyuki Kusaka University of Tsukuba Computational sciences empowering heat island research

15:00-15:15 Break Part II: How to support "Trusted Researches"?

Design Division, Japan Patent Protection of intellectual property right - Focusing on design 15:15-15:45 Tokie Tani Office examination system -

15:45-16:15 Kaori Yamaguchi University of Tsukuba Coaching with integrity

16:15-16:45 Koji Okabayashi University of Tsukuba Research management and academic integrity

National Institute for Materials 16:45-17:15 Shinya Uji How can research be trusted? Science

17:15-17:45 Hajime Nagahara ASAHI KASEI CORPORATION An example; R&D management in industry

17:45 Tadashi Baba University of Tsukuba Closing

* The official language of the Symposium will be Japanese. * The abstracts are distributed in the separate booklet at the conference room.

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100 Spiritual and Physical Exercises in Eastern and Western Philosophies

Faculty of Humanities and Social Sciences, University of Tsukuba

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

101 Sep 28 (Sun) Meeting Room 3

Spiritual and Physical Exercises in Eastern and Western Philosophies

Chair Yoshinori Tsuzaki University of Tsukuba

Prospectus for the Session Spiritual and Physical Exercises in Eastern 13:30-13:40 Yoshinori Tsuzaki University of Tsukuba and Western Philosophies

Leonard Willem Johannes The Spiritual Teacher in Tibet: 'Gos Lo tsā ba Gzhon nu dpal's (1392- 13:40-14:10 Harvard University van der Kuijp 1481) Assessment of His Master Vanaratna (1384-1468)

Chinese Theory of Mind's Transformation and Gottlieb Spizel's De re 14:10-14:40 Yoshitsugu Igawa University of Tsukuba literaria Sinensium commentarius

14:40-15:10 Martin Delhey University of Hamburg On the Place of Knowledge in Ancient Indian Buddhist Spiritual Practice

15:10-15:30 Break Chair Chizuko Yoshimizu University of Tsukuba

Practicing Ethics and Purifying the Mind: the 'Four Immeasurables' - an 15:30-16:00 Michael Zimmermann University of Hamburg Early Buddhist Spiritual Exercise

Thomas Aquinas and Dionysius the Areopagite - The Relationship 16:00-16:30 Yoko Ito University of Tsukuba between the Creator and the Creature -

Diaries, Religious Experience, and Philosophical Change of Ludwig 16:30-17:00 Akio Kikai University of Tsukuba Wittgenstein

17:00-17:10 Break

17:10-17:20 Naoki Kuwabara University of Tsukuba General Remark

17:20-17:50 Closing Discussion

102

1 / 26 ページ Sep 28 (Sun) Meeting Room 3

Spiritual and Physical Exercises in Eastern and Western Philosophies

Chair Yoshinori Tsuzaki University of Tsukuba

Prospectus for the Session Spiritual and Physical Exercises in Eastern 13:30-13:40 Yoshinori Tsuzaki University of Tsukuba and Western Philosophies

Leonard Willem Johannes The Spiritual Teacher in Tibet: 'Gos Lo tsā ba Gzhon nu dpal's (1392- 13:40-14:10 Harvard University van der Kuijp 1481) Assessment of His Master Vanaratna (1384-1468)

Chinese Theory of Mind's Transformation and Gottlieb Spizel's De re 14:10-14:40 Yoshitsugu Igawa University of Tsukuba literaria Sinensium commentarius

14:40-15:10 Martin Delhey University of Hamburg On the Place of Knowledge in Ancient Indian Buddhist Spiritual Practice

15:10-15:30 Break Chair Chizuko Yoshimizu University of Tsukuba

Practicing Ethics and Purifying the Mind: the 'Four Immeasurables' - an 15:30-16:00 Michael Zimmermann University of Hamburg Early Buddhist Spiritual Exercise

Thomas Aquinas and Dionysius the Areopagite - The Relationship 16:00-16:30 Yoko Ito University of Tsukuba between the Creator and the Creature -

Diaries, Religious Experience, and Philosophical Change of Ludwig 16:30-17:00 Akio Kikai University of Tsukuba Wittgenstein

17:00-17:10 Break

17:10-17:20 Naoki Kuwabara University of Tsukuba General Remark

17:20-17:50 Closing Discussion

103

1 / 26 ページ Prospectus for the Session Spiritual and Physical Exercises in Eastern and Western Philosophies

Yoshinori Tsuzaki

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

In his highly praised book Philosophy as a Way of Life, Pierre Hadot, one of the most eminent French historians of Western philosophy in the last five decades, deftly articulates the distinction between the social function of ancient and modern philosophy in Europe. “Ancient philosophy proposed to mankind an art of living. By contrast, modern philosophy appears above all as the construction of a technical jargon reserved for specialists.”1 According to him, the ultimate purpose of this “art of living” is “to transform the whole of the individual’s life.”2 Such transformation is accomplished in everyday life by undertaking so-called spiritual exercises. As Habot notes in a different book:

By this term [spiritual exercises], I mean practices which could be physical, as in dietary regimes, or discursive, as in dialogue and meditation, or intuitive, as in contemplation, but which were all intended to effect a modification and a transformation in the subject who practices them.3

Whether we accept the adequacy of Hadot’s account of the history of philosophy or not4, in considering these exercises we may be encouraged to not only reconsider what Western philosophy should be today, but also to further understand Eastern thoughts in which the Western way of separating philosophy from religion seems less easy to accomplish. From there, we are able to criticize the distinction between religion and philosophy, since religion should be practically inseparable from these exercises. In other words, it is still important for today’s humanity studies, to analyze, from the diachronic and synchronic points of view using the comparative method, how practices and discourses have developed in different types of philosophies and religions, focusing on acts unique to mankind: spiritual and physical exercises. Our session aims, firstly, to use philological analysis of primary sources to understand how practices and discourses on these exercises can be characterized in each of the three cultural spheres: India, China, and Europe. Secondly, we try to describe, by using the comparative method, the differences and similarities between these spheres. In the process of this analysis are we able to identify any commonalities in exercises developed, seemingly independently, in the Western and Eastern spheres of influence without ignoring the specifics of each philosophy and religion? This question will be discussed by Japanese specialists, including young researchers of Confucianism, Christianity, and Western modern philosophy from the University of Tsukuba as well as foreign scholars of Buddhism from the University of Hamburg and Harvard University.

1 Pierre Hadot, Philosophy as a Way of Life, trans. by Michael Chase, Oxford: Blackwell, 1995, p. 272. 2 Ibid., p. 265. 3 Pierre Hadot, What is Ancient Philosophy?, trans. by Michael Chase, Cambridge, MA: Harvard UP, 2002, p. 6. 4 See one of the latest collections of critical essays on this question: Michael Chase, at al. eds., Philosophy as a Way of Life: Ancients and Moderns: Essays in Honor of Pierre Hadot, Oxford: Wiley-Blackwell, 2013.

104 The Spiritual Teacher in Tibet: ‘Gos Lo tsā ba Gzhon nu dpal’s (1392-1481) Assessment of His Master Vanaratna (1384-1468)

Leonard W. J. van der Kuijp

Department of South Asian Studies, Harvard University

The notion of spirituality is complex and highly nuanced, being very much related to ideas we entertain about the nature and the varieties of religious experience. Crucial in its conceptu- alization from a Buddhist perspective is the notion of the spiritual teacher (guru, Tib. bla ma) and his or her [or even its role – the world (loka, Tib. ‘ jig rten) as a teacher] who functions as a guide during one’s “spiritual cultivation” (bhavana). Towards the end of the first millennium of the common era, an individual variously called Rta dbyangs [*Aśvaghoṣa] or Bha vi lha [*Bhavideva] wrote a little text in fifty quatrains titled theGurupañcāsika . The complete text of this work is available in two Tibetan translations and in one Chinese translation – he is there called Maming馬鳴 [*Aśvaghoṣa] –, and only a fragment is extant in Sanskrit. In this talk, I will first briefly discuss this work as well as the identity of its rather mysterious author on the basis of two rare manuscripts that deal with him. Much of the contents of this work is based on those chapters titled “Inquiring into the Characteristics of the Spiritual Teacher” that we find in many esoteric, tantric Buddhist texts. Numerous Tibetan commentaries also exist on this work, but only one Indian one, namely, the one that was probably written by the great scholar Vanaratna (1384-1468). This work was translated by his disciple ʻGos Lo tsā ba Gzhon nu dpal (1392-1481). ʻGos Lo tsā ba was also the author of this master’s biography. He makes a pause about two-thirds into this biography to reply to a question raised by an unknown individual to the effect why he would write a biography of this master, given that he had so many other great teachers. My talk will close with an analysis of his answer, since it sheds interesting light on the ideas of spirituality and the spiritual teacher.

105 Chinese Theory of Mind’s Transformation and Gottlieb Spizel’s De re literaria Sinensium commentarius

Yoshitsugu Igawa

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

The Jesuit missionaries who visited China in the 16-18th century translated the Confucian classic four books (「四書」). The Protestant pastor Spizel in the 17th century, acquired their information, wrote research document about Chinese philosophy De re literaria Sinensium commentarius. This book introduced information of the philosophy and the religion in China, Chinese characters and hexagrams (易卦) in Book of Changes (『易経』) as a universal sign - incidentally young Leibniz read through this book when he wrote De Arte combinatoria. The fundamental view of the world and idea of Confucianism appear in the Great Learning (『大 学』) of the four books. The book asserts the change of the heart by inductive grasp of uni- versal natural laws, and perfection of the others and the world. With reference to this, Spizel presented the originality of Chinese philosophy as contrasted with the view of the European philosophy. Furthermore, Spizel explained about the reason for being of all things (Ratio), the world development by the combination of the binary multiplication (binarium multiplicatis) of hexagrams, monad concerned with a numeration in the Chinese philosophy. In this regard, empirical research based on the Eastern and Western literatures is expected. In this presenta- tion is announced its preliminary research result.

106 On the Place of Knowledge in Ancient Indian Buddhist Spiritual Practice

Martin Delhey

Centre for the Study of Manuscript Cultures, University of Hamburg

Specialists in Indian Buddhism still disagree widely on the question of which teachings found in the oldest sources can or cannot be regarded as authentic words of the historical founder of Buddhism and on the problem how to interpret them. However, one general state- ment made by the Austrian Indologist Erich Frauwallner in his Philosophy of Buddhism (Delhi 2010, p. 12) certainly meets with relatively small resistance in the academic community:

Above all else, he [i.e. the Buddha, M.D.] is imbued with a passionate urge to find liberation from the suffering of existence. The philosophical teaching activities of his time, on the other hand, repelled him. […] As far as possible, he rejects theoretical discussions, providing only the reasons for entanglement in the suffering of existence and the possibility of liberation in a few formulaic sentences.

It is, indeed, hardly imaginable that the historical Buddha Siddhārtha Gautama would have found anything valuable in modern philosophy as characterized by Pierre Hadot (see his Philosophy as a Way of Life or What is Ancient Philosophy?). Instead, one can easily find many spiritual exercises and practical instructions for living the life of a Buddhist ascetic in his teachings that served the goal to attain final liberation from mundane existence. The lecture will, however, not exclusively restrict itself to the earliest times. There can be no doubt that Buddhism later in its history contributed enormously to the development of Indian and Asian philosophy. In the present context, it is especially interesting to note that in the centuries surrounding the beginning of the common era, highly sophisticated edifices of Buddhist scholasticism developed. Therefore, in the second part of the lecture I would like to examine to what extent these developments were still in line with the pronouncedly practical and pragmatic approach taken by Siddhārtha Gautama. Moreover, I will try to answer on the basis of select sources the question what place knowledge and theory occupied in some varie- ties of Buddhist systematized soteriology and religious practice.

107 Practicing Ethics and Purifying the Mind: the ‘Four Immeasurables’ ― an Early Buddhist Spiritual Exercise

Michael Zimmermann

Numata Center for Buddhist Studies, University of Hamburg

The paper will deal with a spiritual exercise from the earliest times of Buddhism in India, called the ‘Four Immeasurables’ (Sanskrit: apramāṇa, brahmavihāra). In this exercise the meditator cultivates and radiates out the four mental/emotional states of loving-kindness, compassion, empathetic joy and equanimity/indifference in all directions. Each of these four states will be analyzed and an interpretation of the likely historical development of the exercise will be attempted. It will become clear that this early exercise combines several salient points of the early Buddhist tradition such as the purification and protection of one’s own mind directed towards a state of eradicating all of its limiting factors, while at the same time having a discernible ethical dimension. The Four Immeasurables as a ‘spiritual technology’ have, in different forms, been employed and innovatively integrated in modern Buddhist meditative practices and therapeutic applications. As a widely followed exercise across the Buddhist traditions, it portrays an alternative way in which the central Buddhist philosophy of ‘Not- Self’ is manifested in a major meditative technique: here the concept of a Self is not eradicated by plain intellectual analysis and insight, but rather through the infinite extension of one’s self- centered emotions leading to the dispersal and ensuing evaporation of the concept of a Self.

108 Thomas Aquinas and Dionysius the Areopagite - The Relationship between the Creator and the Creature -

Yoko Ito

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

French Dominican theologian Gilles Emery O.P. argues that the theology of St. Thomas Aquinas (ca. 1225–1274) is regarded as a spiritual exercise in which the practitioner of theol- ogy is a pilgrim seeking wisdom and, ultimately, a union with triune God1. Thomas, who is one of the greatest representatives of Scholasticism, had been recognized only as the “Aristo- telian” figure. However we also have to remember the name of “Dionysius the Areopagite”. Dionysius, the early sixth-century “Christian” writer who used the name of Paul’s first convert in Athens, eventually effected a marriage between Christianity and Neoplatonism. We can find out one of the most important examples of this marriage in the thought of Thomas. Fa- ther Andrew Louth, a priest of the Russian Orthodox Church says: “St. Thomas Aquinas read Denys with great care and attention: and whole areas of his theology – the doctrine of divine attributes, angelology, to name but two – are deeply in debt to him”2. My talk aims to clarify the understanding of Thomas about the relationship between the Creator and the Creature in the Summa Theologiae. In order to account for this dimension I will analyze in particular questions 3-13 in S.T. with the support of Thomas’s commentary on Dionysius’ Divine Names.

1 His short presentation of this argument is found in the essay: Gilles Emery, “Trinitarian Theology as Spiritual Exercise in Augustine and Aquinas,” in Aquinas the Augustinian, edited by Michael Dauphinais, Barry David, and Matthew Levering, Washington, D.C.: Catholic University of America Press, 2007. 2 Andrew Louth, Denys the Areopagite, London: Geoffrey Chapman, 1989, p. 126.

109 Diaries, Religious Experience, and Philosophical Change of Ludwig Wittgenstein

Akio Kikai

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

Ludwig Wittgenstein (1889-1951) is one of the most well-known philosophers of our age. He was born in Vienna and acted as a philosopher in Austria and England. Throughout his life, the major object of his philosophical interest had been logic and language. However, his view on these subjects radically changed in the second half of his philosophical career, so the researchers usually talk as if there were two Wittgenstein’s: early Wittgenstein and later Wittgenstein. These two views were represented in his two major works: Tractatus Logico- philosophicus and Philosophical Investigations. In the former, which was written in his 20’s, he tried to give a philosophical foundation for Frege’s formal logic and all scientific languages based on it. According to it, our language is essentially a tool for describing the world and it is possible because there is a structural parallelism between the world and our language. This view, which was also held by Galileo and may sound attractive to many modern scientists as well, was to be completely thrown away by him in his later philosophy. The work in which he described and developed his second view is Philosophical Investigations. According to it, human language including our mathematics is not something that reflects the essential structure of the world, but a part of human mutual activities in which our actual life consists. He calls each unit of these activities with language a “language game”. So natural sciences and mathematics are not the mirror of nature in themselves, but a system of various human language games like chess or football. How the same philosopher can hold such radically different views in his life had been just a mystery for long time since there were so few materials from which we could construct the answer for it. However, his diaries written in 1936-37, in which the most important part of Philosophical Investigations was written, were made public by the heir of his most intimate friend who had inherited some important manuscripts of Wittgenstein in 1993. These diaries are casting a completely new light onto the study of Wittgenstein. In my talk, I, as a translator of diaries into Japanese, want to show what lay behind his philosophical change.

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112 Frontier Studies of Policy and Planning Sciences

Department of Policy and Planning Sciences, Graduate School of Systems and Information Engineering, University of Tsukuba

113 Sep 28 (Sun) Multimedia Room

Frontier Studies of Policy and Planning Sciences (Students Presentations)

Chair Stephen Turnbull University of Tsukuba

16:00-16:15 Berdymyrat Ovezmyradov University of Tsukuba Traditional Turkmen Textiles: Consumer Properties and Market

A Lagrangian Relaxation Algorithm for Modularity Maximization 16:15-16:30 Kotohumi Inaba University of Tsukuba Problem

Packing: Distributed TDMA MAC protocol with Spatial Reuse for 16:30-16:45 Kouhei Moriyama University of Tsukuba Wireless Sensor Networks

16:45-17:00 Michio Matsubayashi University of Tsukuba Using BIM for Conversion of Design Documents into Electronic Form

Forest cover change detection using multi-source data analysis in 17:00-17:15 Taohong Zou University of Tsukuba Daxing’anling Mountain during 2000 to 2010

Considerations about the Strategy that cut down the cost to maintain 17:15-17:30 Xindi Zhang University of Tsukuba sideway trees’ function

Beautiful city image: suggestions from the constructions of green 17:30-17:45 Benyan Jiang University of Tsukuba spaces in Qingdao (1898-1938)

Restoration of Nairobi River Basin and Creation of a Vibrant Riverfront 17:45-18:00 Melissa Wanjiru University of Tsukuba Development Zone Lessons from Tokyo’s Sumida River

114

8 / 26 ページ Sep 28 (Sun) Multimedia Room

Frontier Studies of Policy and Planning Sciences (Students Presentations)

Chair Stephen Turnbull University of Tsukuba

16:00-16:15 Berdymyrat Ovezmyradov University of Tsukuba Traditional Turkmen Textiles: Consumer Properties and Market

A Lagrangian Relaxation Algorithm for Modularity Maximization 16:15-16:30 Kotohumi Inaba University of Tsukuba Problem

Packing: Distributed TDMA MAC protocol with Spatial Reuse for 16:30-16:45 Kouhei Moriyama University of Tsukuba Wireless Sensor Networks

16:45-17:00 Michio Matsubayashi University of Tsukuba Using BIM for Conversion of Design Documents into Electronic Form

Forest cover change detection using multi-source data analysis in 17:00-17:15 Taohong Zou University of Tsukuba Daxing’anling Mountain during 2000 to 2010

Considerations about the Strategy that cut down the cost to maintain 17:15-17:30 Xindi Zhang University of Tsukuba sideway trees’ function

Beautiful city image: suggestions from the constructions of green 17:30-17:45 Benyan Jiang University of Tsukuba spaces in Qingdao (1898-1938)

Restoration of Nairobi River Basin and Creation of a Vibrant Riverfront 17:45-18:00 Melissa Wanjiru University of Tsukuba Development Zone Lessons from Tokyo’s Sumida River

115

8 / 26 ページ Traditional Turkmen Textiles: Consumer Properties and Market

Berdymyrat Ovezmyradov

Policy and Planning Sciences Program, Graduate School of Systems and Information Engineering, University of Tsukuba

The purpose of this research was to evaluate traditional Turkmen textiles’ properties which were the most important for consumers and to study the corresponding market in Turkmenistan. The focus was on women’s clothing since, unlike males, females so far remained the frequent users of traditional clothing. The research was implemented in a sequential order. A mixed method was applied using both quantitative (physical tests and a survey) and qualitative (interviews and observations) techniques. Interviews were conducted first. Then, the questionnaire was developed and distributed among respondents. Afterwards, tests of fabric samples were conducted in textile labs according to DIN ISO standards. Finally, the comparative analysis of garments was implemented. Functionality, durability, safety, ease of care, image, popularity, affordability, availability, expedience and aesthetic properties were chosen for evaluation as the most important properties for consumers. Panbarhat and Keteni, two types of widely used dresses, were found to have both low clothing comfort and excessively high costs for an average consumer. On the other side, popular Shtapel dresses were found to be substantially more affordable and comfortable. The study showed how attitudes towards wearing clothing among Turkmen consumers seemed to be constrained by social and cultural influences, specifically by ideals of modesty. A comparative analysis of consumers’ preferences for clothing was implemented comparing Germany and Turkmenistan. Overall, the comparison showed that for Turkmen consumers aesthetic properties of clothing had the higher priority while practical aspects such as functionality and comfort had a relatively lower significance. Those results indicated issues in consumption of textiles and clothing among the Turkmen population and revealed an issue of changing consumption patterns in a way that boosts acceptance of more comfortable and economic clothing.

116 A Lagrangian Relaxation Algorithm for Modularity Maximization Problem

Kotohumi Inaba1, Yoichi Izunaga1 and Yoshitsugu Yamamoto2

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

The modularity proposed by Newman and Girvan is one of the most common measures when the nodes of a graph are grouped into communities consisting of tightly connected nodes. Due to the NP-hardness of the problem, few exact algorithms have been proposed. Aloise et al. formulated the problem as a set partitioning problem, which has to take into account all, exponentially many, nonempty subsets of the node set, and makes it difficult to secure the computational resource when the number of nodes is large. Their algorithm is based on the linear programming relaxation, LP relaxation for short, and uses the column generation technique. Although it provides a tight upper bound of the optimal value, it can suffer a high degeneracy due to the set partitioning constraints. In this study, we propose an algorithm based on the Lagrangian relaxation. We relax the set partitioning constraints and add them to the objective function as a penalty with Lagrangian multipliers, and obtain the Lagrangian relaxation problem with only the binary variable constraints. For a given Lagrangian multiplier vector, an optimal solution of the Lagrangian relaxation problem can be obtained by checking the sign of coefficients, but it is hard to compute all the coefficients of variables. Then we propose to use the column generation technique in order to alleviate the computational burden. Namely, we start the algorithm with a small number of variables and gradually add variables as the computation goes on. We also propose some methods to accelerate the convergence.

117 Packing: Distributed TDMA MAC protocol with Spatial Reuse for Wireless Sensor Networks

Kouhei Moriyama1 and Yongbing Zhang1,2

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

A time division multiple access (TDMA) channel control approach is an efficient method for large-scale wireless sensor networks, especially when the network is congested. However, it is generally difficult to allocate the time slots to the nodes in a distributed way. Recently, a distributed approach called TreeMAC (Song W-Z et al., Pervasive and Mobile Computing 5: 750-765, 2009) is proposed wherein the sink node allocates the required time slots of each node that is connected to the sink depending on the number of its children. Each node then recursively allocates the time slots to its children. The key disadvantage of TreeMAC is its low channel efficiency. In this paper, we propose a packing (called PACK) algorithm that tries to find the unused time slots for additional traffic demand. The proposed protocol is composed of two phases, say, information collection and free time-slot search phases. Firstly, in the information collection phase, each node collects the interference information within its two- hop neighbors expect its grandchildren. Then, in the free time-slot search phase each node reserves free time slot(s) incrementally. The PACK algorithm is triggered by a leaf node with the least node identification number. The node reserves its required time slots according to the traffic demand, and sends the results to its parent. A parent which receives the reservation numbers from all of its children does the same process, and it sends the slot numbers of it and its children to its parent. If the number of a sensor’s available slots is less than its slot demand, the parent deletes the enough slots reserved to ensure its slot demand, or adds enough new time slots. The simulation results show that the PACK protocol significantly improves not only the channel efficiency but also the network throughput and the energy consumption in comparison with TreeMAC.

118 Using BIM for Conversion of Design Documents into Electronic Form

Michio Matsubayashi1 and Shun Watanabe2

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

The conservation of building stock constructed during the period of high economic growth is the urgent problem in Japan. Paper media had been used for the design documents to con- struct those buildings. Now, these design documents are often unusable for their renovation and conversion, since they are deteriorated or sometimes lost. It is urgent to convert them into electronic form for the conservation of building stock. Building Information Modeling (BIM) is the state of the art technology of recording design information to 3D model. As the case study, we have converted old drawings and specifications of University of Tsukuba to the BIM model for saving design information. Our previous study treated the comparison between paper media and BIM model, and examined the difference between them. Design documents are classified into “Architecture”, “Structure” and “Mechanical/Electrical/Plumbing (MEP)”. In paper media, drawings of “MEP” are less numerous than those of “Architecture” and “Structure” in vertical section. As for vertical section, the position of “MEP” elements are described and managed in different forms, such as distribution diagrams of plumbing. The problem of conversion into the BIM model was found, since the BIM model requires the exact 3D data of these elements. On the other hand, the conversion methods from the BIM models to traditional drawings was also confirmed. The BIM model can produce plan drawings by cutting it horizontally. It can also produce elevation and section by cutting it perpendicularly. However, it is difficult to grasp the connection between “MEP” elements because they are placed complexly in the BIM model. The method of generating distribution diagram of plumbing is necessary for the effective facility management, because we can easily grasp the placement of “MEP” elements in traditional forms. Creating of the program to generate a distribution diagram from the BIM model is our next work. The challenge is to grasp the whole network by following connection information, because attribute information about their connection is inherent and concealed in the objects of “MEP” elements. We plan to extract data by using API of the software and create a distribu- tion diagram by repositioning these. The utility of the BIM model as the means to save design information will improve by the conversion method of distribution diagram being realized.

119 Forest cover change detection using multi-source data analysis in Daxing’anling Mountain during 2000 to 2010

Taohong Zou and Kunihiko Yoshino

Graduate school of System and Information Engineering, University of Tsukuba

Abstract: Forest cover change is an important part of global environmental change, which could induce a series of bad effects to the environment. And the forest cover change detection is indispensable for sustainable forest management. Considering the Moderate Resolution Imaging Spectro-radiometer (MODIS) can provide global vegetation condition in a large temporal and spatial scale, it plays a significant role in monitoring the vegetation change. In this paper, a decision tree was built based on the phenology features of vegetation extracted from the MODIS EVI products, Land surface temperature and topographic condition to get the forest cover map in Daxing’anling Mountain in 2000 and 2010. Then the statistical analysis is conducted to detect the forest cover change in the area. Results showed that the area of needle forest is decreasing and the portion of mixed forest and shrub is increasing, and the forest cover change mainly happened in the southern and northern part in the area where the human activities are more active.

Key words: forest cover change; decision tree; MODIS; Daxing’anling Mountain

120 Considerations about the Strategy that cut down the cost to maintain sideway trees’ function

Xindi Zhang

Graduates School of System & Information Engineering, Master’s Program in Social Systems Engineering, University of Tsukuba

Government spends large amount of budget on managing sideway trees, but these years public work-related expenditures that can be spent on the maintenance of them are shrinking. We can see trees be pruned badly so they won’t need any prunetrim for some years. But those trees on the streets losing their elegant appearance makes none sense as a sideway tree. How- ever, the tax used spent on supporting each sideway tree is limited by the decreasing popula- tion. Years later, the management of sideway trees will be a heavy burden, especially to those small municipalities. The goal of this research is to find the if there is an optimum strategy to cut down managing cost of sideway trees, in other words, to reduce the trees, but still keep their multiple functions. One of the way to decide a tree’s necessity is to divide by functions of sideway trees, that is to say, who can benefit from them. Sideway trees could improve the environment by preventing hot-island effect, absorbing noise, and eliminate Carbon dioxide eliminating; they could contribute to urban landscape and protect walkers from the burning sun; and they could also guide direction for drivers. Another way to considering the sequence we decrease the number of sideway trees is from the condition that they are in. First, to con- sider those roads whose traffic or users decreased a lot in the past years; second, to consider to plan sideway trees for those roads surrounding by green land as a background that the amount of green land had already been secured; third, to conduct the chosen of tree types depend on its’ suitability of land development.

121 Beautiful city image: suggestions from the constructions of green spaces in Qingdao (1898-1938)

Benyan Jiang

Researcher in Graduate School of Human Comprehensive Sciences, University of Tsukuba

Qingdao, which was governed by Germany, Japan and Republic of China from 1898 to 1938, was honored as “the most beautiful city in China” before WWII. This paper aims to examine how Qingdao was constructed into such a beautiful city and try to get some inspirations from its development process. I found that first of all, the beautiful city image was a result of accumulated ideas of different governors. Since urban planning theories started to be widely accepted through the world, ideal city concepts such like hygienic city and park city were gradually proposed by the German governors and Japanese governors in the first phases of urban constructions in Qingdao. Thanks to this common goal and continuous efforts of different governors, lots of green spaces were constructed before WWII. Secondly, Qingdao is endowed with hills and sea, which are really precious resources to create beautiful city landscape. Fortunately, the German governors realized that since the very beginning, and started to create forests both on hills and along seaside rather than houses. Forestation activities were also continued by the governors of Japan and Republic of China, which not only solved the soil erosion and the shortage of drinking water but also provided a green background to the whole city. As for parks, firstly, they were mainly arranged around significant public facilities such as government office, church and railway station during the German period. These facilities even now are often landmarks of a city and parks around helped to strengthen their significant status and create much more beautiful landmark scape. On the other hand, colonial rule led to an unequal distribution of parks as well. The situation of no parks built in the Chinese area was not improved until Qingdao was recovered by the Republic of China.

122 Restoration of Nairobi River Basin and Creation of a Vibrant Riverfront Development Zone Lessons from Tokyo’s Sumida River

Melissa Wanjiru1, Kosuke Matsubara2

1PhD Candidate, Doctoral Program in Policy and Planning Sciences, University of Tsukuba 2Associate Professor, Department of Policy and Planning Sciences, University of Tsukuba

Nairobi city has an immense potential for waterfront development owing to the fact that it is traversed by three rivers (Mathare, Nairobi and Ngong’) which make up the Nairobi river basin. However, there has been continued degradation of the riparian environment, principally because of uncontrolled discharge of domestic and industrial waste into the river. In addition, poor enforcement of the existing environmental laws such as the Environmental Management and Co-ordination Act – EMCA (1999) and the Water Act (2002) has exacerbated the situation. The challenge of riparian degradation notwithstanding, there is a great potential for riverfront development along this river basin. There have been notable efforts towards restoration of Nairobi River and these include: KENSUP (Kenya Slum Upgrading Program) to alleviate slums; the Nairobi River Basin Project (1999) spearheaded by UNEP; and the current Nairobi Rivers Rehabilitation and Restoration Programme (2010). This paper was an attempt to highlight the Sumida River restoration programme and the subsequent successful riverfront development as a benchmark for Nairobi river basin. This was done in consideration of the local peculiarities of the two sites. This comparative analysis’ intent is to contribute to the knowledge that will enable creation of a Nairobi riverfront design that will lead to socio-economic and environmental benefits.

Key words: Nairobi River Basin, Sumida River, restoration, riverfront design and development

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124 Japan and the World after 3.11

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

Graduate School of Business, MBA Program in International Business, University of Tsukuba

125 Sep 28 (Sun) 5C216

Japan and the World after 3.11

Chair Takafumi Ohtomo University of Tsukuba

Yutaka Tsujinaka University of Tsukuba 13:00-13:10 Introduction Takafumi Ohtomo University of Tsukuba

Formerly Nissan Professor of 13:10-13:30 Arthur (J. A. A.) Stockwin Modern Japanese Studies, The Impact of the 3/11 Disasters on Domestic Japanese Politics University of Oxford

National Graduate Institute for 13:30-13:50 Kiyoshi Kurokawa Japan and the World After 3.11: Quo Vadis Policy Studies

(Tentative) Japan after Great Earthquake –View from Former Prefectural University of 13:50-14:10 Makoto Iokibe Chairman of Reconstruction Design Council in Response to Great East Kumamoto Japan Earthquake–

14:10-14:30 Yutaka Tsujinaka University of Tsukuba Japan after the Great Earthquake: Exploring Public Decision Making

14:30-16:00 Dicussion, Q&A

Chair Remy Magnier-Watanabe University of Tsukuba

16:00-16:05 Remy Magnier-Watanabe Introduction

Yoshinoya and It’s Cause-Related Marketing Initiative post-3.11: When 16:05-16:30 Caroline Tan University of Tsukuba Risk and Trust Affect Consumer Behavior

Foreign exchange and market value of Japanese firms: a threshold co- 16:30-16:55 Jean-Claude Maswana University of Tsukuba integration estimation

Developing Next Generation of the Global Leaders 16:55-17:20 Hirohisa Nagai University of Tsukuba -Endeavor for Creating a New Global Education Program-

17:20-17:30 Short Break

17:30-18:00 Panel Discussion

*Order of presentation subject to change.

126

9 / 26 ページ Sep 28 (Sun) 5C216

Japan and the World after 3.11

Chair Takafumi Ohtomo University of Tsukuba

Yutaka Tsujinaka University of Tsukuba 13:00-13:10 Introduction Takafumi Ohtomo University of Tsukuba

Formerly Nissan Professor of 13:10-13:30 Arthur (J. A. A.) Stockwin Modern Japanese Studies, The Impact of the 3/11 Disasters on Domestic Japanese Politics University of Oxford

National Graduate Institute for 13:30-13:50 Kiyoshi Kurokawa Japan and the World After 3.11: Quo Vadis Policy Studies

(Tentative) Japan after Great Earthquake –View from Former Prefectural University of 13:50-14:10 Makoto Iokibe Chairman of Reconstruction Design Council in Response to Great East Kumamoto Japan Earthquake–

14:10-14:30 Yutaka Tsujinaka University of Tsukuba Japan after the Great Earthquake: Exploring Public Decision Making

14:30-16:00 Dicussion, Q&A

Chair Remy Magnier-Watanabe University of Tsukuba

16:00-16:05 Remy Magnier-Watanabe Introduction

Yoshinoya and It’s Cause-Related Marketing Initiative post-3.11: When 16:05-16:30 Caroline Tan University of Tsukuba Risk and Trust Affect Consumer Behavior

Foreign exchange and market value of Japanese firms: a threshold co- 16:30-16:55 Jean-Claude Maswana University of Tsukuba integration estimation

Developing Next Generation of the Global Leaders 16:55-17:20 Hirohisa Nagai University of Tsukuba -Endeavor for Creating a New Global Education Program-

17:20-17:30 Short Break

17:30-18:00 Panel Discussion

*Order of presentation subject to change.

127

9 / 26 ページ The Impact of the 3/11 Disasters on Domestic Japanese Politics

Arthur (J.A.A.) Stockwin

Formerly Nissan Professor of Japanese Studies and Director, Nissan Institute of Japanese Studies; Emeritus Fellow, St. Antony’s College, University of Oxford

The triple disasters of 11th March 2011, of earthquake, tsunami and nuclear meltdown, took an enormous toll in human lives and in a crisis of radiation near the Fukushima nuclear reac- tors. The aim of this presentation, however, will be to assess the impact of the crisis, both short term and long term, on the domestic politics of Japan. The crisis took place around eighteen months after the long political dominance of the Lib- eral Democratic Party (LDP) had been broken in the elections of August 2009, which produced a new government headed by the Democratic Party of Japan (DPJ), founded only 13 years ear- lier. The handling of the disasters by the DPJ leader and Prime Minister, Kan Naoto, became a matter of acute controversy, which I shall briefly discuss. But a broader question is how far 3/11 contributed to the eventual downfall of the DPJ government in the decisive elections of December 2012. This is complicated, because the government had already created doubts about its competence under its first prime minister, Hatoyama Yukio, with his inept handling of the Futenma Marine Base issue in Okinawa. Some weeks after the disasters Kan was re- placed by a third DPJ prime minister, Noda Yoshihiko, who presided over a sharp deterioration in relations between Japan and China over ownership of the Senkaku (Diaoyu) islands. It is therefore difficult to argue that it was 3/11 that brought down the DPJ government, though it undoubtedly played some part. I shall also examine the political impact, under the Abe Government, of nuclear power plant closure and threatened reopening, and will conclude that this issue has served to revive long moribund movements of popular political opposition, as well as enhancing conflict be- tween central and local governments.

128 Japan and the World After 3.11: Quo Vadis

Kiyoshi Kurokawa

Academic Fellow, National Graduate Institute for Policy Studies, Tokyo.

The world is in a major historical transition in coming few decades from the Principles built since Industrial Revolution to something quite Uncertain. Knowledge dissemination and rapid progress in science and technology have been critical elements underlying such a major change as our history shows. Two major factors bringing this big transition are explosion of Human Population from 1.6 billion in year 1900 to more than 7 billion in recent years and Hyper-Connectivity. The status of the world of globalization becomes rapidly changing, frag- mented and fragile. Examples of major buzz words we often see these days include; Resilience, Risks, while 'Accountability and Transparency' have become essential to the governance of any organization, institution and government. Fukushima Nuclear Accident of 3.11, 2011, was a 'Black Swan Event' hit by huge earth- quake and tsunami; many official and independent investigation reports, books, documentaries have been published in Japan and in abroad. Fukushima Nuclear Accident Independent Investigation Commission (NAIIC) by the Na- tional Diet, launched 9 months after the Accident, was FIRST of such kind in Constitutional Democratic Japan, NAIIC turned out to be a 'While Body Scan of the Governance of Japan Inc.,’ revealing Inconvenient Truth to many in the 'Establishment' of Japan. In this session I discuss the Change of the Status of the World and Japan and choices and opportunities ahead of you.

References for copy distribution 1. http://naiic.go.jp ; NAIIC Reports in both Japanese and English 2. naiic.net/; Easy to understand NAIIC report in animation videos, 6 x 3 minutes each. 3. kiyoshikurokawa.com/

129 Yoshinoya and It’s Cause-Related Marketing Initiative post-3.11: When Risk and Trust Affect Consumer Behavior

Caroline Tan

MBA-International Business, Graduate School of Business Sciences, University of Tsukuba

Cause-related marketing is a strategy that has appeals to corporations, as it not only re- sponds to societal pressure for ‘corporate social responsibility’ but at the same time it also shareholders’ pressure for profits. This practice of the advocacy of corporate social respon- sibility in marketing activities has witnessed a surge in corporations adopting it as offers the ‘win-win’ solution to both profit and non-profit alike. Nielsen conducted a corporate social responsibility study in 2014 and the results showed that 64% of the Asia-Pacific respondents indicated their willingness to pay extra for products and services that are committed to positive social and environmental impact. In 2013, Yoshinoya announced that it will start cultivating rice and other vegetables through a joint-venture with local farmers in Fukushima with an investment of ¥10 million beginning 2014. This move was aimed at lowering costs and im- proving the supply chain and at the same time contribute to the reconstruction of Fukushima post 3.11. Using the Theory of Reasoned Action this study examines the consumers’ attitude towards Yoshinoya’s cause-related marketing initiative and its impact on consumer behavior. While cause-related marketing has been positively effective in influencing consumer behav- ior, the findings of this study proved otherwise. The results indicate that factors of trust and perceived risk play a major role in determining consumption and purchase decisions. Interest- ingly, the element of personal impact and implication influenced the consumers’ decisions and showed that unlike the majority of cause-related marketing initiatives that proved to be success stories, Yoshinoya’s decision could bring about a negative effect.

Keywords: Cause-related marketing, Trust, Perceived Risk, Consumer Behavior, Theory of Reasoned Action

130 Foreign exchange and market value of Japanese firms: a threshold co-integration estimation

Jean-Claude Maswana

MBA-International Business, Graduate School of Business Sciences, University of Tsukuba

Measuring foreign exchange has been a critical issue both in theoretical literature related to international financial management and in the regular operations of multinational firms, especially Japanese ones. As major Japanese firms derive nearly half of their sales from over- seas markets, impacts of foreign exchange fluctuation on their performance (in terms of market value). While the assessment of such impacts has been theoretically well-documented, how- ever, empirical studies have been providing conflicting evidence. This is so, in part, because of econometrics misspecification related to the application of linear models. Yet, it is increas- ingly admitted that the linear models cannot explain a number of important features common to much financial data. Building on recent developments in nonlinear econometrics models, the present study empirically investigates exchange rate exposure of Japanese firms whose performance (measured by aggregate market value) highly depends on exchange rate changes using threshold cointegration estimation. The primary finding is that stock market and foreign exchange are asymmetrically cointegrated with stock prices being significantly exposed to exchange rate changes in depreciation regimes. The result has some implication for policy in the post-March 11 Japan, especially as the most direct way that Abenomics has helped firms is through lowering the value of the yen.

131 Developing Next Generation of the Global Leaders -Endeavor for Creating a New Global Education Program-

Hirohisa Nagai, Ph.D.

MBA-International Business, Graduate School of Business Sciences, University of Tsukuba

Japanese society has been encountering the various aspects of challenges on dealing with the globalization for past decade. Among those, developing competent global leaders is one of the most demanding topics for Japanese business society. Contrary to that rapidly emerging issue, the current status of the Japanese companies’ training and developing for global leaders is ranked at the tail end among twelve advanced and semi-advanced countries (Tsukuba Global HRD Research Unit, 2013). In fact, training opportunity for next generation of the global leaders has been decreasing. For example, number of high school students studied in abroad (>3 months) has decreased by 22% between 1998 and 2011 (MEXT, 2012). Also, Japan’s TOEFL score was ranked at #28 among 30 Asian countries in 2011. According to the survey results on the Japan’s high school programs conducted by the Japan Institute for Social and Economic Affairs (2013), there are eight issues that hindering to acquire the global savvy in the current system. This survey result indicated that the causes of these issues are likely due to the discrepancies between the current educational system (traditional) and the ideal conditions (future-oriented). It also proposed the importance of 1. Introduce the liberal arts education, 2. Transfer course units after returning from studying at the overseas, and 3. Reform the contents of college entrance examination to meet the global perspectives. Objectives of this study is to propose a new framework for developing next generation of the global leaders based on the SPDL (Search-Plan-Do-Learn) model combined with the research results of the meta-cognitive approach of learning global leadership competency (2013). This revised model will provide a new horizon of developing problem solving skills, a key global leadership competency. Implications from this study will include a new training and development program as well as pedagogy to educate next generation of the global leaders.

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133 NOTE

134 Student Presentations – The 9th Tsukuba Medical Science Research Meeting –

Faculty of Medicine, University of Tsukuba Ph.D. Program in Human Biology, University of Tsukuba Tsukuba Society for Molecular Medicine/TSMM

135 Sep 29 (Mon) International Conference Room

Student Presentations -The 9th Tsukuba Medical Science Research Meeting-

9:00-9:05 Introduction

Assessment of drug therapy efficacy for pregnancy-induced 9:05-9:18 Haojun Xu University of Tsukuba hypertension using genetically modified mouse model

Induction of associative olfactory memory by targeted activation of the 9:18-9:31 Takato Honda University of Tsukuba memory circuits in Drosophila larvae

The pontomedullary tegmentum GABAergic neurons regulate the 9:31-9:44 Daiki Nakatsuka University of Tsukuba states of sleep and wakefulness

9:44-9:57 Imke Jenniches University of Bonn Cannabinoid signaling in stress and depression: the role of DAGLα

Mating controls female germline stem cell proliferation via steroid 9:57-10:10 Tomotsune Ameku University of Tsukuba hormone biosynthesis in Drosophila melanogaster

Ferroxidase activity of staphylococcal MrgA is essential for oxidative 10:10-10:23 Yuri Ushijima University of Tsukuba stress resistance

10:23-10:40 Coffee Break Multisystem functional characterisation of motile ciliopathy genes 10:40-10:53 Girish Mali University of Edinburgh HEATR2 and ZMYND10

USP15 regulates neuromuscular functions mediated by the control of 10:53-11:06 Jaehyun Kim University of Tsukuba RNA splicing

11:06-11:19 Daniel Quang Unviersity of California, Irvine Motif signatures in stretch enhancers

11:19-11:32 Yen-Yun Chen Unviersity of California, Irvine The role of NIPBL in Cornelia de Lange Syndrome

Marine-derived antiviral compound eudistomin C is a protein 11:32-11:45 Keisuke Yoshida University of Tsukuba translation inhibitor

11:45-11:58 Nathana Barbosa Lopes University of Sao Paulo Floral fluorescent dyes and derivatives for cell staining

Redesign of the colicin E7 nuclease domain into a controlled and 11:58-12:11 Eszter Németh University of Szeged specific artificial enzyme

136

13 / 26 ページ Sep 29 (Mon) International Conference Room

Student Presentations -The 9th Tsukuba Medical Science Research Meeting-

9:00-9:05 Introduction

Assessment of drug therapy efficacy for pregnancy-induced 9:05-9:18 Haojun Xu University of Tsukuba hypertension using genetically modified mouse model

Induction of associative olfactory memory by targeted activation of the 9:18-9:31 Takato Honda University of Tsukuba memory circuits in Drosophila larvae

The pontomedullary tegmentum GABAergic neurons regulate the 9:31-9:44 Daiki Nakatsuka University of Tsukuba states of sleep and wakefulness

9:44-9:57 Imke Jenniches University of Bonn Cannabinoid signaling in stress and depression: the role of DAGLα

Mating controls female germline stem cell proliferation via steroid 9:57-10:10 Tomotsune Ameku University of Tsukuba hormone biosynthesis in Drosophila melanogaster

Ferroxidase activity of staphylococcal MrgA is essential for oxidative 10:10-10:23 Yuri Ushijima University of Tsukuba stress resistance

10:23-10:40 Coffee Break Multisystem functional characterisation of motile ciliopathy genes 10:40-10:53 Girish Mali University of Edinburgh HEATR2 and ZMYND10

USP15 regulates neuromuscular functions mediated by the control of 10:53-11:06 Jaehyun Kim University of Tsukuba RNA splicing

11:06-11:19 Daniel Quang Unviersity of California, Irvine Motif signatures in stretch enhancers

11:19-11:32 Yen-Yun Chen Unviersity of California, Irvine The role of NIPBL in Cornelia de Lange Syndrome

Marine-derived antiviral compound eudistomin C is a protein 11:32-11:45 Keisuke Yoshida University of Tsukuba translation inhibitor

11:45-11:58 Nathana Barbosa Lopes University of Sao Paulo Floral fluorescent dyes and derivatives for cell staining

Redesign of the colicin E7 nuclease domain into a controlled and 11:58-12:11 Eszter Németh University of Szeged specific artificial enzyme

137

13 / 26 ページ Sep 28 (Sun), 29 (Mon) Exchange Hall 12:11-13:40 Break Poster Display (Student Presentations, Global Aging Center Tsukuba) 13:40-14:15 2-min presentation P-1 to P-14 P-1 Min Li The effect of different soil utilizition on the RIP of 137Cs contaminated soil from northern Japan 14:15-14:25 Coffee Break P-2 Anna Ignatochkina Function characterization of a second and novel mRNA capping apparatus in Trypanosoma brucei 14:25-14:38 Tomokazu Kimura University of Tsukuba GPNMB impacts to invasive properties of bladder cancer The genetic compatibility among influenza virus polymerase subunits for the generation of reassortant P-3 Yoshimi Harada viruses Cooperative expression of transmembrane prostate androgen induced 14:38-14:51 Thanh Thao Vo Nguyen University of Tsukuba P-4 Tomomi Fukuda A Cullin-related protein regulates posttranslational modification of PML protein –TMEPAI by TGF-β and EGF signaling

Genetic depletion and pharmacological targeting of αv integrin in P-5 Tatsuya Komura-Kawa A novel transcriptional regulation of steroid hormone biosynthesis in Drosophila melanogaster 14:51-15:04 Yihao Li Leiden University breast cancer cells impairs metastasis in zebrafish and mouse xenograft models P-6 Yuto Masuda The budding yeast AMPK ortholog Snf1 negatively regulates endoplasmic reticulum stress response Challenges for sustainable tomato production: Isolation of a novel tomato mutant with enhanced fruit P-7 Hitomi Takei 15:04-15:17 Antoniana Batsivari University of Edinburgh Analysis of proliferation in hematopoietic stem cell development set efficiency and candidate gene approaches by Next Generation Sequencing Construction of genetic analysis available multidrug sensitive yeast strain by both the disruption of P-8 Takumi Chinen drug efflux system and the conditional repression of membrane barrier system 15:17-15:30 Pei-Han Tai National Taiwan University SIK2 controls dynamics of insulin production in pancreatic β cells P-9 Taito Miyachi Involvement of the small GTPase Arf6 in PDGF-induced dorsal ruffling

P-10 Ngo Thai Bich Van Tumor-infiltrating CD8 T lymphocytes are decreased in Phospholipase D2 knockout mice 15:30-15:43 Tran Thi Nhu Mai University of Tsukuba MafB deficiency impairs the apoptotic cell clearance of macrophages P-11 Ling Zheng Role of THG-1 in tumor angiogenesis through stabilization of HIF-1α in normoxic condition 15:43-15:55 Coffee Break P-12 Kazuya Ito Dormant cancer cells have high reserved antioxidant capacity that may promote their radioresistance 15:55-16:30 2-min presentation P-15 to P-27 P-13 Shota Sakaguchi Non-invasive in vivo near-infrared fluorescent imaging of tumors with iRFP 16:30-17:20 Poster Session (Exchange Hall) P-14 Miki Shimbo Chondrodysplasia in mice lacking both chondroitin sulfate N -acetylgalactosaminyltransferase-1 and -2 A meta-analysis of experimental studies of radiation attenuated 17:20-17:33 Mizuho Fukushige University of Edinburgh schistosome vaccines in the animal model P-15 Zeinab Kosibaty MafB regulates macrophage-osteoclast progenitor cell function

The effect of temperature on all-cause mortality in the three P-16 Ahmed Abdellatif MafK overexpression impairs pancreatic β-cells development in vivo 17:33-17:46 Xerxes Seposo University of Tsukuba metropolitan cities in the Philippines, 2006-2010 P-17 Yunshin Jung The role of large maf transcription factors in the β-like cell conversion from mouse liver The early marriage and maternal health care utilization in rural 17:46-17:59 Md. Harunor Rashid University of Tsukuba Bangladesh: Analysis of Bangladesh Demographic Health Survey P-18 Jian-Huang Lin NPM1 functions as a subunit of enhanceosome for NF-κB-mediated transcription

Relationships of family function, QOL and family empowerment of the P-19 Yu Ishikawa Involvement of oviductal peristalsis in fertilization of the mouse 17:59-18:12 Keiko Yamaguchi University of Tsukuba family rearing a child with severe motor and intellectual disabilities at Identification and characterization of human CD300H, the eighth member of the CD300-family home P-20 Kouta Niizuma receptors How a group-based anger-management parenting program changed 18:12-18:25 Hiromi Tobe University of Tsukuba P-21 Eri Takenaka DNAM-1 (CD226) plays an important role in antigen presentation by small peritoneal macrophages mothers’ cognition, attitude and behavior P-22 Haruka Miki The role of CD300a (MAIR-I) in allergic airway inflammation

P-23 Tran B. Nguyen Somatic mosaic mutations in TET2 and DNMT3A in a case of peripheral T-cell lymphoma Association of leukocyte immunoglobulin-like receptor A3 (LILRA3 ) deletion polymorphism with P-24 Yuki Hachiya systemic sclerosis Association of TRIM21 (RO52 ) polymorphisms with systemic lupus erythematosus in a Japanese P-25 Misaki Hidaka population P-26 Miki Kagami Temperature during pregnancy influences birth size

P-27 Tomoko Suga The intervention research on Domestic Violence prevention program for high school students

138

6 / 26 ページ 14 / 26 ページ Sep 28 (Sun), 29 (Mon) Exchange Hall 12:11-13:40 Break Poster Display (Student Presentations, Global Aging Center Tsukuba) 13:40-14:15 2-min presentation P-1 to P-14 P-1 Min Li The effect of different soil utilizition on the RIP of 137Cs contaminated soil from northern Japan 14:15-14:25 Coffee Break P-2 Anna Ignatochkina Function characterization of a second and novel mRNA capping apparatus in Trypanosoma brucei 14:25-14:38 Tomokazu Kimura University of Tsukuba GPNMB impacts to invasive properties of bladder cancer The genetic compatibility among influenza virus polymerase subunits for the generation of reassortant P-3 Yoshimi Harada viruses Cooperative expression of transmembrane prostate androgen induced 14:38-14:51 Thanh Thao Vo Nguyen University of Tsukuba P-4 Tomomi Fukuda A Cullin-related protein regulates posttranslational modification of PML protein –TMEPAI by TGF-β and EGF signaling

Genetic depletion and pharmacological targeting of αv integrin in P-5 Tatsuya Komura-Kawa A novel transcriptional regulation of steroid hormone biosynthesis in Drosophila melanogaster 14:51-15:04 Yihao Li Leiden University breast cancer cells impairs metastasis in zebrafish and mouse xenograft models P-6 Yuto Masuda The budding yeast AMPK ortholog Snf1 negatively regulates endoplasmic reticulum stress response Challenges for sustainable tomato production: Isolation of a novel tomato mutant with enhanced fruit P-7 Hitomi Takei 15:04-15:17 Antoniana Batsivari University of Edinburgh Analysis of proliferation in hematopoietic stem cell development set efficiency and candidate gene approaches by Next Generation Sequencing Construction of genetic analysis available multidrug sensitive yeast strain by both the disruption of P-8 Takumi Chinen drug efflux system and the conditional repression of membrane barrier system 15:17-15:30 Pei-Han Tai National Taiwan University SIK2 controls dynamics of insulin production in pancreatic β cells P-9 Taito Miyachi Involvement of the small GTPase Arf6 in PDGF-induced dorsal ruffling

P-10 Ngo Thai Bich Van Tumor-infiltrating CD8 T lymphocytes are decreased in Phospholipase D2 knockout mice 15:30-15:43 Tran Thi Nhu Mai University of Tsukuba MafB deficiency impairs the apoptotic cell clearance of macrophages P-11 Ling Zheng Role of THG-1 in tumor angiogenesis through stabilization of HIF-1α in normoxic condition 15:43-15:55 Coffee Break P-12 Kazuya Ito Dormant cancer cells have high reserved antioxidant capacity that may promote their radioresistance 15:55-16:30 2-min presentation P-15 to P-27 P-13 Shota Sakaguchi Non-invasive in vivo near-infrared fluorescent imaging of tumors with iRFP 16:30-17:20 Poster Session (Exchange Hall) P-14 Miki Shimbo Chondrodysplasia in mice lacking both chondroitin sulfate N -acetylgalactosaminyltransferase-1 and -2 A meta-analysis of experimental studies of radiation attenuated 17:20-17:33 Mizuho Fukushige University of Edinburgh schistosome vaccines in the animal model P-15 Zeinab Kosibaty MafB regulates macrophage-osteoclast progenitor cell function

The effect of temperature on all-cause mortality in the three P-16 Ahmed Abdellatif MafK overexpression impairs pancreatic β-cells development in vivo 17:33-17:46 Xerxes Seposo University of Tsukuba metropolitan cities in the Philippines, 2006-2010 P-17 Yunshin Jung The role of large maf transcription factors in the β-like cell conversion from mouse liver The early marriage and maternal health care utilization in rural 17:46-17:59 Md. Harunor Rashid University of Tsukuba Bangladesh: Analysis of Bangladesh Demographic Health Survey P-18 Jian-Huang Lin NPM1 functions as a subunit of enhanceosome for NF-κB-mediated transcription

Relationships of family function, QOL and family empowerment of the P-19 Yu Ishikawa Involvement of oviductal peristalsis in fertilization of the mouse 17:59-18:12 Keiko Yamaguchi University of Tsukuba family rearing a child with severe motor and intellectual disabilities at Identification and characterization of human CD300H, the eighth member of the CD300-family home P-20 Kouta Niizuma receptors How a group-based anger-management parenting program changed 18:12-18:25 Hiromi Tobe University of Tsukuba P-21 Eri Takenaka DNAM-1 (CD226) plays an important role in antigen presentation by small peritoneal macrophages mothers’ cognition, attitude and behavior P-22 Haruka Miki The role of CD300a (MAIR-I) in allergic airway inflammation

P-23 Tran B. Nguyen Somatic mosaic mutations in TET2 and DNMT3A in a case of peripheral T-cell lymphoma Association of leukocyte immunoglobulin-like receptor A3 (LILRA3 ) deletion polymorphism with P-24 Yuki Hachiya systemic sclerosis Association of TRIM21 (RO52 ) polymorphisms with systemic lupus erythematosus in a Japanese P-25 Misaki Hidaka population P-26 Miki Kagami Temperature during pregnancy influences birth size

P-27 Tomoko Suga The intervention research on Domestic Violence prevention program for high school students

139

6 / 26 ページ 14 / 26 ページ Oral Presentation

O-1

Assessment of drug therapy effi cacy for pregnancy-induced hypertension using genetically modifi ed mouse model

Haojun Xu1,2, Junji Ishida2, Tomohiro Ishimaru2, Altansarnai Baasanjav2, Misuzu Hashimoto1,2, Kazuyuki Noguchi2,3, and Akiyoshi Fukamizu1,2

1Ph. D. Program in Human Biology, School of Integrative and Global Majors, University of Tsukuba 2Life Science Center, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba 3Department of Nephrology, Faculty of Medicine, University of Tsukuba

Pregnancy-induced hypertension (PIH) is characterized by elevated blood pressure accompanied with the signifi cant amount of protein in the urine in the second or third trimester of pregnancy. This syndrome brings high risk to both maternal and fetal health, while the molecular mechanism of the pathogenesis remains unclear. It is reported that L-type calcium channel (LCC) on smooth muscle cell plays a dominant role in regulation of vasoconstriction. Hence, dihydropyridine, a basic structure of LCC specifi c blocker (LCCBs), is widely used in chronic hypertension therapy but not to PIH patients because of the ethical diffi culties for examining the drug effect including unknown risk on mothers and fetuses. In this research, we aim to evaluate the pharmaceutical effect of LCCB on the above pathology using pregnancy-associated hypertensive (PAH) mice, an animal model for PIH. By treating amlodipine, one kind of dihydropyridine LCCB, to PAH mice, blood pressure was suppressed in a dose-dependent manner. Urinary protein level was also reduced to the level of normal pregnancy. In addition, cardiac abnormality and placental structure were partially ameliorated, while fetal intrauterine growth retardation is not affected by amlodipine. These results suggested a variety of ameliorative effects of LCCB on the progressive pathologies during pregnancy-associated hypertension in mice.

140 Oral Presentation

O-2

Induction of associative olfactory memory by targeted activation of the memory circuits in Drosophila larvae

Takato Honda1,2, Chi-Yu Lee2, Maki Yoshida-Kashikawa2, Ken Honjo2,3, and Katsuo Furukubo-Tokunaga2

1Ph.D. Program in Human Biology, School of Integrative and Global Majors, University of Tsukuba 2Graduate School of Life and Environmental Sciences, University of Tsukuba 3National Institiute of Genetics

The fruit fl y Drosophila melanogaster has been used as a model animal for the study of the genetic and molecular mechanisms of learning and memory. Appetitive olfactory memory is formed in Drosophila by at least two sets of external stimuli, conditioned odor stimuli (CS) mediated by the olfactory receptor neurons (ORNs) and unconditioned reward stimuli (US) mediated by the octopaminergic (OA) neurons. Previous works showed that synaptic output from OA neurons is necessary for appetitive memory formation. Signals of OA neurons are integrated with the olfactory information pathway at antennal lobes and mushroom bodies, to establish appetitive associative memory trace. However, whether associative memory can be induced by the activation of only the olfactory CS and a biogenic amine-mediated US pathways remains to be elucidated. With its simple neuroanatomical design, the larval brain of Drosophila can be utilized as an excellent model system for the elucidation of the neurocircuitry mechanism of memory. In this study, we took the advantages of optogenetic and thermogenetic techniques. We substituted sugar reward stimuli by thermogenetic activation of OA neurons with the dTrpA1 channel, and odor stimuli by optical activation of a specifi c class of ORNs with Channelrhodopsin-2 (ChR2). We showed that targeted activation of the converging memory circuitry with blue light and heat produces associative memory in the transgenic larvae. We also showed that memory thus produced is specifi c to the odorant determined by the type of the activated ORNs. Furthermore, we demonstrated that this artifi cial memory persists for medium term, and as stable as natural memory produced by using a real odorant. Our results thus provide direct evidence that targeted stimulation of only a single type of olfactory receptor neurons is suffi cient to induce olfactory memory that is indistinguishable from natural memory induced by the activation of multiple ORNs (Honda T et al., Scientifi c Reports, 2014). Given its simplicity and robustness, this method could be utilized to further our knowledge on the neurocuircuitry mechanisms of memory.

141 Oral Presentation

O-3

The pontomedullary tegmentum GABAergic neurons regulate the states of sleep and wakefulness

Daiki Nakatsuka1, Takeshi Kanda1, Tatsuya Kurokawa1, and Masashi Yanagisawa1,2

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

The states of sleep and wakefulness are regulated by several subcortical regions including the brainstem. The medulla oblongata is thought to contain the neural circuits responsible for sleep. However, the detailed cellular and systems level mechanisms are poorly understood. Here, we focused on GABAergic neurons in the pontomedullary tegmentum. To determine whether and how they contribute to the regulation of sleep states, we specifi cally manipu- lated their fi ring patterns and traced their projection patterns. Cell-type and location specifi c gene delivery was achieved by local injection of Cre- inducible adeno-associated virus vectors (AAV) into the pontomedullary tegmentum of GAD1-Cre mice in which Cre recombinase is expressed specifi cally in GABAergic neurons. To silence their fi ring, inhibitory DREADD hM4Di was targeted to them. In patch-clamp experiments, bath application of the hM4Di agonist CNO suppressed their discharge in brain slices. Total time of NREM sleep after intraperitoneal administration of CNO was markedly increased in the mice in which hM- 4Di was expressed in the dorsal area of pontomedullary tegmentum, whereas comparatively little effect on sleep pattern was observed in the mice expressing hM4Di in the medial area. Spectral analysis of EEG activity showed that EEG power, especially delta power (1-4 Hz), during NREM sleep was markedly decreased in the mice expressing hM4Di in the dorsal area, but not in the medial area. To elucidate the anatomical basis for the control of sleep states by the dorsal pontomedullary tegmentum GABAergic neurons, we traced their axonal fi bers with GFP appended to a palmitoylation sequence of GAP43. Their axons were found not only in the medulla, pons and midbrain, but also in the thalamic reticular nucleus which is thought to be a sleep spindle pacemaker. These results suggest that GABAergic neurons in the dorsal pontomedullary tegmentum connect with the thalamocortical networks and contribute to the regulation of sleep states.

142 Oral Presentation

O-4

Cannabinoid signaling in stress and depression: the role of DAGLα

Imke Jenniches, Svenja Ternes, Andras Bilkei-Gorzo, and Andreas Zimmer

Institute of Molecular Psychiatry, University of Bonn, Germany

Depression is a highly prevalent psychiatric disorder and is associated with high levels of morbidity and mortality. Even though the knowledge of the pathophysiology of depression has evolved signifi cantly in the last decades, vast gaps still remain in the comprehension of depression and its treatment. The endogenous cannabinoid system plays a modulatory role in many cognitive and emotional processes and is therefore strongly involved in neuropsychiatric disorders. For instance, long-term treatment with rimonabant, the fi rst clinically used cannabinoid receptor 1 (CB1) antagonist, showed adverse psychiatric side effects in patients including anxiety and depression. In rodents the genetic or pharmacologic blockade of CB1, the major neuronal cannabinoid receptor, increases depression- and anxiety-like behavior. The two main endogenous cannabinoids, anandamide and 2-arachidonoylglycerol (2- AG), bind to presynaptic CB1 receptor and thereby inhibit the secretion of both excitatory and inhibitory neurotransmitters. The key enzyme for the formation of 2-AG, the most abundant endocannabinoid in the brain, is diacylglycerol lipase α (DAGLα). We assume that the absence of DAGLα, and thus the lack of 2-AG, leads to a depressive-like phenotype that is similar to that observed in CB1 knockout mice. To investigate the role of DAGLα in different cell types, we recently generated constitutive, as well as microglia- and neuron-specifi c knockout mice and tested these animals in various anxiety- and depression-related behavior tests. Our fi rst results indicate that DAGLα knockout mice are more prone to stress than wildtype controls and therefore very likely more susceptible to develop a depression-like phenotype after exposure to chronic stress.

143 Oral Presentation

O-5

Mating controls female germline stem cell proliferation via steroid hormone biosynthesis in Drosophila melanogaster

Tomotsune Ameku1, Yuko Shimada-Niwa1, and Ryusuke Niwa1,2

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

In animals, mating is a pivotal behavior to produce offspring in the next generation and to achieve prosperity of species. In many insect species, mating elicits a number of critical changes in female reproductive behavior, such as an increase of egg-laying (Heifetz Y et al., Curr Biol 10:99-102, 2000). Whereas behavioral changes in mated females are well studied, it is still unclear how physiological changes are controlled by mating. To address this question, we used the fruit fl y Drosophila melanogaster as a model organism. Here we show a relationship between post-mating oogenesis and the major insect steroid hormone ecdysteroid. We found that mating induce an increase in the number of female germ- line stem cells (GSCs). We also found that ecdysteroid level in the adult ovary is signifi cantly elevated after mating. To examine whether post-mating ecdysteroid biosynthesis in the ovary is crucial for controlling female GSC numbers, we created 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 post- mating increase of not only ovarian ecdysteroid titer but also female GSC numbers. Impor- tantly, the GSC phenotype was rescued by oral administration of 7dC. These results suggest that post-mating ecdysteroid biosynthesis in the ovary plays a pivotal role in controlling GSC proliferation in adult Drosophila female. Our study illustrates a role of ecdysteroids in the adaptive maintenance of female GSC numbers, which might contribute to positively activating oogenesis after mating.

144 Oral Presentation

O-6

Ferroxidase activity of staphylococcal MrgA is essential for oxidative stress resistance

Yuri Ushijima1, Ryosuke L. Ohniwa1, Shinji Saito1, Yoshikazu Tanaka2, and Kazuya Morikawa1

1Microbiology, Faculty of Medicine, University of Tsukuba 2Creative Research Institution Sousei, Hokkaido University

Staphylococcus aureus MrgA (encoded by mrgA) belongs to Dps family proteins that play important roles to cope with a broad range of stresses. The staphylococcal mrgA gene is spe- cifi cally expressed under oxidative stress conditions and is one of the most highly induced ones during phagocytic killing by macrophages. We previously reported that mrgA is essential for oxidative stress resistance, and can cause nucleoid compaction. However, whether nucleoid compaction by itself would contribute to oxidative stress resistance was elusive, because Dps family proteins generally have ferroxidase activity to prevent the hydroxyl radical formation via Fenton reaction. In the present study, we solved the crystal structure of MrgA and conduct- ed mutation analysis of Asp56 and Glu60 that locate at the expected ferroxidase center. In the mrgA* strain that expresses Asp56Ala/Glu60Ala MrgA (MrgA*), MrgA* retained dodecamer formation and nucleoid compaction ability. On the other hand, the ferroxidase activity of MrgA* decreased about half. Viability of the mrgA* strain was as low as the mrgA null mutant in oxidative stress, and phagocytic killing assays. These results suggest that nucleoid compac- tion by itself is not suffi cient for oxidative stress resistance, and Asp56 and Glu60 constitute essential molecular site in MrgA for oxidative stress resistance and survival against phagocytic killing.

145 Oral Presentation

O-7

Multisystem functional characterisation of motile ciliopathy genes HEATR2 and ZMYND10

Girish Mali1,2, Ian Jackson1, Andrew Jarman2, and Pleasantine Mill1

1MRC Human Genetics Unit, MRC IGMM, University of Edinburgh, UK 2Centre for Integrative Physiology, Hugh Robson Building, University of Edinburgh, UK

Cilia are polarized extensions of the cells microtubule-based cytoskeleton dedicated to sensory, signaling and motility-related functions. They are essential for development and adult homeostasis and loss of cilia formation or function leads to a spectrum of human disorders called ciliopathies. In mammals, there are two main types of cilia, immotile and motile, where motile cilia generate fl uid fl ow at the embryonic node, in the airways, cerebral ventricles and the oviduct in addition to sperm propulsion via the fl agellum. Ciliary specialization correlates with an ancient transcriptional code, which has been fi ne-tuned over evolution. Core ciliary genes are transcriptionally activated by members of the winged-helix transcription factor RFX family. The forkhead transcription factor FOXJ1 additionally activates motility genes such as the ones encoding dynein motors which generate the ciliary beat in an ATP-dependent manner. Thus, RFX3 and FOXJ1 co-operatively switch on a genetic programme required to make motile cilia. Mutations affecting this genetic programme lead to a congenital motile ciliopathy called Primary Ciliary Dyskinesia (PCD). Using the highly conserved RFX-FOX transcriptional code, we identifi ed two putative PCD candidates CG31320/HEATR2 and CG11253/ZMYND10 through expression analysis in Drosophila. Conserved roles in ciliary motility were confi rmed with fl y mutant analysis in parallel to identifi cation and characterization of human PCD mutations in these genes. Proteomic studies are underway to defi ne the interaction networks for each of these distinct assembly factors required to deliver functional dynein motor protein complexes to the cilia. Preliminary results for CRISPR mutant mice, generated in collaboration with Prof. Takahashi and Dr. Mizuno (University of Tsukuba) will be presented.

146 Oral Presentation

O-8

USP15 regulates neuromusucular functions mediated by the control of RNA splicing

Jaehyun Kim, Fuminori Tsuruta, and Tomoki Chiba

Graduate School of Life and Environmental Sciences, University of Tsukuba

Alternative pre-mRNA splicing plays an important role in protein diversity and complexity. It enables eukaryotic cells to produce a huge number of proteins from restricted genes through the selective elimination of introns and exon rejoining, and thereby contributes to tissue-specifi c gene functions. In brain, alternative splicing constitutes the basis for neuronal functions regulated by gene expression. Given the importance of alternative mRNA splicing in regulating neuronal functions, it is hardly surprising that disruption of RNA splicing leads to neuronal dysfunction. Indeed, recent studies have revealed that disruption and misregulation of RNA splicing result in neuromuscular disorders such as amyotrophic lateral sclerosis and spinal muscular atrophy. However, the molecular mechanism of how the failure in RNA splicing leads to neuromuscular disorder is yet to be elucidated. In this study, we found that deubiquitinating enzyme, ubiquitin specifi c peptidase 15 (USP15), is associated with neuromuscular functions via the control of RNA splicing. USP15 defi cient mice exhibit ataxia-like behaviors resulting from the morphological defect of cerebellum and skeletal muscle. We also found that USP15 is involved in a deubiquitinization of particular target, which plays a key role in RNA splicing. Furthermore, loss of USP15 widely affects splicing patterns of substantial genes potentially associated with neuromuscular disorders. Taken together, these data suggest that loss of USP15 may bring about aberrant gene expression mediated by misregulation of RNA splicing, and thereby impairs neuromuscular functions. Therefore, this study is expected to be a novel clue for clarifying the relationship between mRNA splicing and neuromuscular diseases.

147 Oral Presentation

O-9

Motif signatures in stretch enhancers

Daniel Quang1,2, Stephen Parker3,4, Peter Chines3, Narisu Narisu3, Brooke Wolford3, Leland Taylor3, Michael Stitzel5, Michael Erdos3, and Francis Collins3

1Department of Computer Science, University of California, Irvine 2Center for Complex Biological Systems, University of California, Irvine 3National Human Genome Research Institute, National Institutes of Health 4Department of Computational Medicine & Bioinformatics, University of Michigan (starting September 1, 2014) 5The Jackson Laboratory for Genomic Medicine, Farmington, CT

Enhancers are regions of DNA where transcription factor proteins bind and modulate transcription of a gene or genes. A cell’s gene expression signature can uniquely identify its cell type. Stretch enhancers are chromatin-defi ned enhancer regions that are much larger (≥3000 DNA base pairs) than typical enhancers (median size = 800 base pairs). They tend to be cell-type specifi c, regulate cell-type specifi c gene expression, and are enriched to co-occur with disease-associated genetic variants, highlighting the importance of stretch enhancers for cellular function. These observations motivated us to investigate molecular signatures that differentiate stretch enhancers from typical enhancers, with a focus on identifying biological insights for why stretch enhancers are so long. To answer these questions, we performed transcription factor motif analyses. Motifs describe the sequence binding preference of transcription factors and can be used to identify the identities and locations of the transcription factors that are binding to these sequences. We developed an experimental and computational approach that can systematically identify stretch and typical enhancers in a cell type at a genome-wide level and applied motif signature analyses to these enhancer sequences. Our analyses across 32 diverse cell types led to the identifi cation of motifs associated with known factors and novel motifs with no known associated factors. Some of these associated factors are well-known “master” transcription factors that are important for establishing cell identity. Many of the genes encoding these master transcription factors also have a nearby, associated cell-type specifi c stretch enhancer that are enriched for potential binding sites for other master transcription factors as well as the transcription factors that the gene encodes. These motifs can therefore be used to generate tight auto-regulatory networks, which we believe is an important mechanism for different cells to maintain their identities. In the future, understanding stretch enhancer motif signatures may lead to targeted engineering of cell-specifi c states.

148 Oral Presentation

O-10

The role of NIPBL in Cornelia de Lange Syndrome

Yen-Yun Chen1, Daniel A. Newkirk1, Ebony Flowers1,5,6, Xiangduo Kong1, Chengguo Yao2, Alex Ball, Jr.1, Richard Chien1, Shimako Kawauchi3, Rosaysela Santos3, Anne L. Calof3, Arthur D. Lander4, Yongsheng Shi2, and Kyoko Yokomori1

1Department of Biological Chemistry, School of Medicine, 2Department of Microbiology & Molecular Genetics, 3Department of Anatomy & Neurobiology, School of Medicine, 4Department of Developmental & Cell Biology, School of Biological Sciences, University of California, Irvine 5California State University Long Beach 6Current address: UT Southwestern Medical Center

Cornelia de Lange Syndrome (CdLS) is an autosomal dominant multisystem developmental disorder characterized by facial dysmorphism, hirsutism, upper limb abnormalities, cognitive retardation, and growth abnormalities. Over 60% of cases are associated with mutations in the NIPBL gene, and NIPBL haploinsuffi ciency is linked to severe cases of CdLS. NIPBL (Nipbl in mice) is required for loading of the essential multiprotein complex “cohesin” onto chromatin. Cohesin mediates sister chromatid cohesion important for mitosis, but is also increasingly being recognized as a regulator of gene expression. In CdLS patient cells and animal models, the presence of multiple gene expression changes with little or no cohesion defect suggests that disruption of gene regulation underlies this disorder. However, the effect of NIPBL haploinsuffi ciency on cohesin binding, and how this relates to the clinical presentation of CdLS, has not been fully investigated. We examined genome-wide cohesin binding and its relationship to gene expression using mouse embryonic fi broblasts (MEFs) from Nipbl +/- mice that recapitulate the CdLS phenotype. We found a global decrease in cohesin binding, including those at CTCF sites and repeat regions. Cohesin-bound genes are enriched for H3K4me3 at the promoters and are mostly downregulated in Nipbl mutant MEFs with evidence for reduced promoter-enhancer interaction, suggesting that gene activation is the primary cohesin function sensitive to Nipbl reduction. Over 50% of genes affected in mutant MEFs are cohesin target genes, including those involved in adipogenesis, indicating that dysregulation of cohesin- target genes directly contributes to the Nipbl haploinsuffi ciency-induced CdLS phenotype. Interestingly, we also found that a subpopulation of Nipbl localizes to the nucleolus and affects ribosomal RNA (rRNA) biosynthesis. Abnormalities in nucleolar function and ribosome biogenesis are known to cause phenotypically similar “ribosomopathies” with growth and mental retardation. Our results raise the possibility that the CdLS phenotype is the result of the combinatorial effects of dysregulation of cohesin target genes and nucleolar function of NIPBL.

This work was supported in part by NIH grants HD052860, HD062951, and HD078849.

149 Oral Presentation

O -11

Marine-derived antiviral compound eudistomin C is a protein translation inhibitor

Keisuke Yoshida1, Yu Ota1, Takumi Chinen1, Ryosuke Yamada2, Hiroshi Masumoto3, Yoko Nagumo1, Satoshi Yokoshima2, Toru Fukuyama2, and Takeo Usui1

1Faculty of Life and Environmental Sciences, University of Tsukuba 2Graduate School of Pharmaceutical Sciences, Nagoya University 3School of Medicine, Graduate School of Biomedical Sciences, Nagasaki University

Eudistomin C (EudiC), a natural product isolated from Caribbean tunicate Eudistoma olivaseum, is an antitumor and antiviral compound. The unique structure and the broad spectrum antiviral activity, for example against Herpes simplex virus type 1, Polio vaccine type 1 virus and so on (Van Maarseveen JH et al. J Med Chem, 35: 3223-3230, 1992), has attracted pharmaceutical companies as a lead compound, but several trial for clinical development of EudiC has failed by its strong cytotoxicity on mammalian cells. Previously we found that the point mutation in rps14A, a component of small subunit of eukaryotic ribosome, conferred the EudiC resistance in budding yeast, and that EudiC inhibited a protein translation in yeast and HeLa cells. These genetical and biochemical results strongly suggest that EudiC is a protein translation inhibitor which binds on ribosome in yeast and mammalian cells. However, the direct interaction of EudiC and ribosome remained to be revealed. In this study, we investigate the EudiC-binding proteins and the direct interaction between EudiC and Rps14 in mammalian cells and yeast. For detection of the EudiC-binding protein, biotinylated photoaffi nity probe of EudiC (EudiC-probe) was synthesized. IC50 values of synthesized EudiC-probe to HeLa cells were almost the same with that of nat ural EudiC. Pull down assay using EudiC-probe from HeLa cell and yeast lysate revealed that there were several binding proteins. Some of the proteins were identifi ed by western blotting and mass spectrometory as ribosomal proteins including Rps14 and Rps5. Furthermore, melting point shifts were observed in the protein denature assay using purifi ed yeast ribosome in the presence of EudiC. These results indicate that EudiC binds to ribosome directly and inhibit protein synthesis in yeast and mammalian cells.

150 Oral Presentation

O-12

Floral fl uorescent dyes and derivatives for cell staining

Nathana Barbosa Lopes1, Renata Rosito Tonelli2, and Erick Leite Bastos1

1Departamento de Química Fundamental, Instituto de Química, Universidade de São Paulo 2Departamento de Ciências Biológicas, Universidade Federal de São Paulo

Betalains are water-soluble vacuolar alkaloids that replace anthocyanins in the pigmentation of some families of plants. According to their chemical structure, these pigments can be subdivided into red-violet betacyanins or yellow betaxanthins. Interestingly, fl owers whose petals are pigmented with betaxanthins are fl uorescent (Gandia-Herrero F et al., Nature 437: 334-334, 2005). Betanin (CI Natural Red 33, E-code E162, hº = 336, betanidin 5-O-β- glucoside) is obtained almost entirely from red beet crops and is the only betalain approved by the FDA for use in food. This betalain has been used in several different applications such as dyes in solar cells (Calogero G et al., Sol Energy 86: 1563-1575, 2012), as a starting material in the semisynthesis of fl uorescent probes for the live imaging ofPlasmodium -infected red blood cells (Gonçalves LCP et al., Plos One 8: e53874, 2013), and for the colorimetric quantifi cation of Bacillus anthracis spores (Gonçalves LCP et al., Plos One 8: e73701, 2013). Herewith we describe the design of non-cytotoxic semisynthetic fl uorescent betalains for the staining of tumor cells and parasites. The dyes were semisynthesized by aldiminic coupling between betalamic acid, obtained from the alkaline hydrolysis of betanin, and adequate amines. The resulting betaxanthins are fl uorescent in aqueous media and relatively stable to hydrolysis in near-neutral pH. Submicromolar concentration of the derivatives bearing electron-withdrawing groups conjugated to the betalainic 1,7-diazaheptamethinic were suitable for the fl uorescent staining of U87 human glioblastoma cells, but not the KATO III human gastric carcinoma cell line. The results suggest that calcium transport may play a role in the internalization and accumulation of the dye in subcellular compartments. Some derivatives were also effective to stain Tripanosoma cruzi, the causative agent of the neglected Chagas disease as well as Giardia lamblia, the fl agellated protozoan parasite that colonizes the duodenum causing giardiasis.

151 Oral Presentation

O-13

Redesign of the colicin E7 nuclease domain into a controlled and specifi c artifi cial enzyme

1 2 2 3 Eszter Németh , Masamitsu Asaka , Kyosuke Nagata , Chris Oostenbrink , and Béla Gyurcsik1,4

1Department of Inorganic and Analytical Chemistry, University of Szeged, Hungary 2Nagata Special Laboratory, Faculty of Medicine, University of Tsukuba, Japan 3Institute of Molecular Modeling and Simulation, University of Natural Resources and Life Sciences, Austria 4MTA-SZTE Bioinorganic Chemistry Research Group, Hungary

Zinc-fi nger nucleases (ZFN) became useful tools for targeted cleavage of genomic DNA. The majority of these chimeric enzymes use the FokI nuclease domain as their hydrolytic unit, fused to the specifi c DNA-binding zinc-fi ngers. Since the DNA binding properties can be redesigned, ZFN-s provide a promising tool as therapeutic agents for monogenetic diseases. However, the cytotoxic side-effect of the presently available ZFN-s prevents such applications. Our research is focused on the design of a safely controlled ZFN being inactive in the absence of the specifi c sequence substrate, while binding to the target DNA induces its active conformation. Instead of the commonly used FokI domain, we fused NColE7 to zinc fi ngers. The fi rst part of the project included the study of the NColE7 protein, which is a bacterial nonspecifi c metallonuclease. Its special structural feature is that its Zn2+-binding C-terminal catalytic domain (HNH-motif) cooperates with the N-terminus of the protein during the enzymatic reaction. We would like to use this feature in the redesign procedure (Czene A et al. J Biol Inorg Chem. 2013,18(3):309-21, Németh E et al. Protein Sci 2014 DOI: 10.1002/ pro.2497). In the following step computational modelling was applied to design the insertion of the zinc-fi ngers in between the N- and C-terminal parts of NColE7 (Németh E et al., J Comput Aided Mol Des 2014 DOI 10.1007/s10822-014-9765-8). Finally, the genes encoding the four designed proteins have been constructed and the proteins were expressed in E.coli cells. The DNA-binding affi nity, specifi city and nuclease activity of the proteins were studied. The most promising model was shown to perform specifi c single strand cuts on the recognition sequence containing plasmid DNA.

152 Oral Presentation

O-14

GPNMB impacts to invasive properties of bladder cancer

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

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

Glycoprotein non-metastatic melanoma protein B (GPNMB) is a type 1 transmembrane glycoprotein. It is expressed in normal tissue and also in cancer cell. Recent evidence de- scribes 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. We examined mRNA and protein expression of GPNMB in nine cell lines using realtime- PCR and western blotting. To investigate how GPNMB contributes to the aggressive pheno- type, we knocked it down by short hairpin RNA or over expressed human GPNMB in invasive bladder cancer cell lines. Cell invasion was examined by the transwell assay with matrigel coating. Every cell line expressed GPNMB mRNA and protein in each manner. There was any relation between GPNMB expression and invasiveness. However, the short hairpin RNA tar- geting GPNMB signifi cantly suppressed invasive ability in bladder cancer cells. Conversely, overexpressing wild type GPNMB greatly promoted invasiveness in these cells. GPNMB is correlated to invasive properties of bladder cancer.

153 Oral Presentation

O-15

Cooperative expression of transmembrane prostate androgen induced protein –TMEPAI by TGF-β and EGF signaling

T hanh Thao Vo Nguyen, Shun Azami, Yukihide Watanabe, and Mitsuyasu Kato

De partment of Experimental Pathology, Graduate School of Comprehensive Human Sciences and Faculty of Medicine, University of Tsukuba, Japan

TMEPAI is a transmembrane protein that was identifi ed as a direct target gene of trans- forming growth factor-β (TGF-β)/Smad signaling. TMEPAI participates in negative feed- back regulation of the duration and intensity of TGF-β/Smad signaling. Moreover, it has been reported that the expression of TMEPAI is also enhanced by EGF signaling; however, the mechanism in which TMEPAI is regulated by EGF signaling remained unclear. Here, we report that TGF-β and EGF signaling cooperatively regulate the transcription of TMEPAI. In addition, expression of TMEPAI in cancer cells was signifi cantly suppressed by MEK kinase inhibitor U016, suggesting that the EGFR/Ras/MAPK pathway involved in the regulation of TMEPAI. There are three ELK-1 binding sites in the fi rst intron of the TMEPAI gene. EGF- induced activation of ELK-1, but not the mutant ELK-1S383A potentiated the TGF-β-induced transcriptional activation of the TMEPAI gene. Mutations in the ELK-1 binding sites ab- rogated the transcriptional activation of a TMEPAI reporter. Furthermore, the Chromatin immunoprecipitation (ChIP) assay reveals that ELK-1 binds to its binding sites in the fi rst intron of the TMEPAI gene in response to EGF signaling. Taken together, these results indicated that the EGF/Ras/ELK-1 pathway, together with TGF-β signaling regulates the expression of TMEPAI.

154 Oral Presentation

O-16

Genetic depletion and pha rmacological targeting of αv integrin in breast cancer cells impairs metastasis in zebrafi sh and mouse xenograft models

Yihao Li1, Yvette Drabsch1, Philippe Pujuguet2, Theo van Laar1, Long Zhang1,4, Hans van Dam1, Philippe Clément-Lacroix2, and Peter ten Dijke1,3

1Department of Molecular Cell Biology, Cancer Genomics Centre Netherlands and Centre for Biomedical Genetics, Leiden University Medical Center 2Galapagos SASU, Romainville 3Ludwig Institute for Cancer Research, Science for Life Laboratory, Uppsala University 4Life Sciences Institute, Zhejiang University

Increased expression of αv integ rins is frequently associated with tumor cell adhesion, migration, invasion and metastasis, and correlates with poor prognosis in breast cancer. However, the mechanism by which αv integrins can enhance breast cancer progression is still largely unclear. The effects of therapeutic targeting of αv integrins in breast cancer also have yet to be in vestigated. In these study, we found that Genetic interference and pharmacological targeting of αv integrin with GLPG0187 in different breast cancer cell lines inhibited their invasion and metastasis in the zebrafi sh xenograft model. Depletion of αv integrin in MDA- MB-231 cells inhibited the expression of the mesenchymal markers and TGF-β pathway. TGF-β induce αv expression and cell migration in MDA-MB-231 cells. In a preclinical mouse model of breast cancer, GLPG0187 inhibited the progression of bone metastasis. Maximum effi cacy of inhibition of bone metastasis was achieved when GLPG0187 was combined with the standard-of-care metastatic breast cancer treatments. These fi ndings show that αv integrin is required for breast cancer metastasis by maintaining the invasive mesenchymal phenotype of the tumor cells. Our results also provide evidence that targeting αv integrin could be an effective therapeutic approach for treatment of breast cancer tumors and/or metastases that overexpress αv integrin.

155 Oral Presentation

O-17

Analysis of proliferation in hematopoietic stem cell development

Antoniana Batsivari, Stanislav Rybtsov, David Hills, Suling Zhao, and Alexander Medvinsky

MRC Centre for Regenerative Medicine, University of Edinburgh, UK

The origin and biology of hematopoietic stem cells (HSCs) during embryogenesis has been an intensely studied topic. Defi nitive HSCs are generated intra-embryonically in the aorta-gonad-mesonephros (AGM) region of the mid-gestation embryo (A. Medvinsky and E. Dzierzak, Cell, 1996). Recent in vitro research revealed that HSCs emerge through a multistep maturation process and are slowly cycling in comparison with the progenitor’s population (S. Taoudi et al., Cell Stem Cell, 2008, S. Rybtsov et al., JEM, 2011; S. Rybtsov et al., 2014). However, the exact role of proliferation during early HSC development remains unclear. Here we used Fucci transgenic mouse lines that enable visualisation of the cell cycle. This system is based on two fl uorescent reporters of cell cycle proteins (Geminin and Cdt1) whose protein levels inversely oscillate during cell cycle (A. Sakaue-Sawano et al., Cell, 2008). Our

functional and phenotypic analysis showed that pre-HSC type I cells mainly reside in G0-G1 phases and thus likely cycle slowly. Meanwhile, pre-HSC type II population appears to be in

both S-G2-M and G0-G1 phases and divides in a synchronised manner. Wholemount staining showed that cells within intra-arterial hematopoietic clusters are predominantly found in

S-G2-M phases, whereas some cells at the base of clusters, which are in close contact with the

vascular endothelium reside in G0-G1 phases. Fetal hematopoietic cells from E14.5 fetal livers were also characterised with regard to their cell cycle status with phenotypic and functional

experiments. Notably, the multipotency of hematopoietic cells could be correlated with G0-G1

cell cycle phases. HSCs in the fetal liver mainly reside in G0-G1 phases, whereas committed

progenitors are found mainly in S-G2-M phases. As expected, HSCs in bone marrow are mainly quiescent. Overall, our data indicate that transition from pre-HSC type I to pre-HSC type II is accompanied by increase in proliferation and that HSCs become progressively quiescent during development.

156 Oral Presentation

O-18

SIK2 controls dynamics of insulin production in pancreatic β cells

Pei-Han Tai1,2, Hisashi Oishi2, Satoru Takahashi2, and Han-Yi Chou1

1Graduate Institute of Oral Biology, National Taiwan University, Taiwan 2Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, Japan

Salt-inducible Kinase 2 (SIK2), is a member of AMPK family, has been reported to play an important role in metabolism and it also regulates cell survival by driving IRS-2 (insulin receptor substrate 2) gene expression upon glucose stimulation. In our group, the SIK2 expression was found in insulin vesicles in cytosol; however, the specifi c function of SIK2 in pancreatic β cells remains unclear. Here we present evidence that the SIK2 participates in regulating insulin secretion. SIK2 is localized to insulin containing large dense-core vesicles and is phosphorylated at residue S587 upon glucose stimulation. This phosphorylation is accompanied by mobilization of the reserved pool insulin vesicles towards the cell periphery for exocytosis. Furthermore, inactivation of SIK2 kinase activity results in unconstrained reserved pool insulin vesicle mobilization and concomitant increase in insulin secretion. Our data suggest that SIK2 participates in regula ting insulin secretion through its kinase activity, which imposes constrain for insulin release. For further examine the physiological relevance of SIK2 in pancreatic β cells, the β cell-specifi c sik2 transgenic mice were generated. Glucose-stimulated insulin secretion test from transgenic mice fed with regular diet showed higher fasting blood glucose and lower insulin secretion compared to control. Consistently, transgenic mice under metabolic stress by feeding high fat diet showed signifi cant decreased in glucose clearance rate. This phenotype revealed that over-expressed SIK2 protein would lead to defect of insulin secretion. In addition, both down-regulation of Ins1 mRNA level and slightly increased α cells, an event in early stage of diabetes, were observed. These collecting phenotypes indicated that the sik2 over-expression might have the tendency for development abnormal glucose homeostasis. Taken together, our results uncovered a novel function of SIK2 in the regulation of insulin secretion in β-cells via insulin vesicle transportation. These fi ndings suggested that SIK2 is an attractive target for developing new strategies for diabetes.

157 Oral Presentation

O-19

MafB defi ciency impairs the apoptotic cell clearance of macrophages

Tran Thi Nhu Mai1,2, Michito Hamada1,2, Risako Shiraishi1, Keigo Asano1,2, and Satoru Takahashi1,2

1Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba 2International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba

Macrophage is one of the main phagocytes recognize and engulf apoptotic cells to main- tain peripheral immune tolerance. The failure of apoptotic cell clearance by macrophages induces autoimmunity. Although most of apoptotic cell recognition factors have been identi- fi ed, the mechanism of transcriptional regulation of these factors remains unknown. MafB is a transcription factor that affects proliferation and differentiation of macrophage. Here we show that MafB involves in apoptotic cells clearance. The deple tion of MafB in macrophage decreases the expression of apoptotic cell recognition genes, especially C1qa, C1qb, C1qc, leads 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. In Mafb-/- mice, production of autoantibody is increased. Our results indicate that MafB might has a pivotal role in phagocytosis of apoptotic cells via C1q regulation.

158 Oral Presentation

O-20

A meta-analysis of experimental studies of radiation attenuated schistosome vaccines in the animal model

Mizuho Fukushige1, Kate M. Mitchell2, Claire D. Bourke3, Mark E.J. Woolhouse1, and Francisca Mutapi4

1Centre for Immunity, Infection and Evolution, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK 2Department of Global Health and Development, London School of Hygiene and Tropical Medicine, London, UK 3Centre for Immunology and Infection, University of York, York, UK 4Institute for Immunology and Infection Research, Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, UK

BACKGROUND: Schistosomiasis is a water-borne parasitic disease of great public health importance. There has been considerable effort for several decades towards the development of a vaccine against schistosomiasis. Numerous animal experimental studies using attenuated schistosome parasites for vaccination have been published since the 1960s. However, these have never been systematically analysed. The aim of this study is to identify measurable experiment conditions that affect the level of protection against re-infection in vaccinated animals. METHODS: Following a systematic review, a total of 957 observations were extracted from 130 articles meeting the search criteria (published 1963-2007). Of these, 755 observations from 106 articles quantifi ed the protective effect of irradiated S. mansoni cercariae vaccination in the mouse model. The analysis was initially conducted using data for S. mansoni in mice, and then expanded to other animal host species (rat and baboon) and other schistosome species (S. haematobium, S. japonicum, and S. bovis). Random effects meta-regression models, weighted by the study size (number of control animals) were used to identify the infl uential predictors. RESULTS: Three predictors were found to have statistically signifi cant effects (P<0.05) on the level of protection: number of immunizing parasites; irradiation dose; and time between the last immunization and challenge. Increasing numbers of immunizing parasites had a positive effect on fraction protected whereas increasing radiation dose and time to challenge infection had negative effects. Comparable results were obtained using data on S. japonicum in mice and S. mansoni in rats. CONCLUSIONS: The models showed that the irradiated cercariae vaccine has a potential of achieving as high as 85% protection with a single vaccination. Protection declines slowly over time but persists for at least 8 months after the last immunization. These fi ndings provide insights into the mechanisms of immunity to schistosome infection and the optimal delivery of attenuated parasite vaccination.

159 Oral Presentation

O-21

The effect of temperature on all-cause mortality in the three metropolitan cities in the Philippines, 2006-2010

Xerxes Seposo1 and Yasushi Honda2

1Graduate School of Comprehensive Human Sciences, University of Tsukuba 2Faculty of Health and Sports Sciences, University of Tsukuba

Effects of temperature on all-cause mortality have been extensively studied in temperate countries such that in US, UK, Japan, Korea and China, but only few studies were carried out in tropical countries in the Southeast Asian region. In the previous study we found out that mortality becomes higher when daily average temperature exceeds 30 degrees Celsius in the National Capital Region. This time-series study explores the effect of temperature on mortality across the three metropolitan cities. Average daily temperature, daily all- cause mortality data, and other daily meteorological parameters were collected from 2006- 2010 from relevant government agencies. We used Poisson regression model accounting for overdispersion in fi tting the city-specifi c effects of daily temperature on daily mortality. Meta- analysis was carried out using mvmeta package of R stastistical programming in analyzing the relationship of temperature on mortality across the cities. Results showed that at Lag 0, the cities are heterogenous from each other compared to the other lags. Meta-regression showed that latitude does not modify the hot effects in the different lags which is in contrast to existing studies. SES (Socioeconomic Status) and education were not included in the study due to data unavailability. Further research is warranted in quantifying the effects of SES and education.

160 Oral Presentation

O-22

The early marriage and maternal health care utilization in rural Bangladesh: Analysis of Bangladesh Demographic Health Survey

Md. Harunor Rashid, Enbo Ma, and Yukiko Wagatsuma

Clinical Trial and Clinical Epidemiology, Graduate School of Comprehensive Human Sciences, University of Tsukuba

Introduction: The marriage before 18 years of age is a major public health problem in both developed and developing countries. The situation of pregnancy and childbirth related morbidity and mortality is worse in Bangladesh because of low utilization of maternal health services. Currently the World Health Organization is emphasized in reviewing and revising policies inproviding access to contraception and reproductive health care services. Objective: This study aimed to explore the relationship between early marriage and utilization of maternal health services inrural Bangladesh. Methods: This study used the Bangladesh Demographic Health Survey (BDHS) database from 1994 to 2011 and extracted out 32,565 maternal cases. The early married categorized as married less than18 years of age. The BDHS had a large sample and internationally accepted method. Results: The early marriage was 89.9% in non-educated women and 25.6% in higher educated women. Compared with adult marriage women, the early marriage women was lower in the contraception utilization (54.4% vs 57.5%, P<0.0001), Antenatal Natal Care (ANC) rate (46.2% vs 69.4%, P<0.0001), and the facility delivery (13.7% vs 39.9%, P<0.0001). Adjusted odd ratio (95% Confi dence Interval) of maternal health service utilization by early marriage women compared with adult marriage women was 0.85 (0.76-0.94) for contraceptive utilization, 1.38 (1.23-1.56) for ANC and 1.4 (1.27-1.71) for facility delivery. Conclusion: The utilization of contraception, ANC and facility deliveries are poorer among the early marriage women than adult marriage women. This information would be useful in reviewing the policies of early marriage.

161 Oral Presentation

O-23

Relationships of family function, QOL and family empowerment of the family rearing a child with severe motor and intellectual disabilities at home

Keiko Yamaguchi1 and Rie Wakimizu2

1Clinical nursing section, Faculty of Nursing Sciences, University of Tsukuba 2Department of Child Health Care Nursing, Division of Health Innovation and Nursing, Faculty of Medicine, University of Tsukuba

There are approximately 36,650 children with severe motor and intellectual disabilities in Japan, on national average about 70% of those lives local life (Ozawa et al., Brain & Development 39;279-282, 2007.). In the family with seriously disabled child, especially primary caregiver, often mother has physical and mental burden immeasurably. We conducted a study on primary caregiver and other family members, focused on their family function, each QOL, and family empowerment by questionnaire. Thirty-three family units participated in our study. The questionnaire included Family Assessment Device (FAD), WHOQOL and KINDLRQOL, and Family Empowerment Scale (FES). Age of seriously disabled child is 4-22 years old. Mean age of primary caregiver is 40.8 years old (range 30-53), 82% of them has become out of condition physically or mentally. All primary caregivers have a role in rearing are mothers. All domains of FAD had a strong correlation with psychological health and social relationships of WHOQOL (each, p˂0.01). And domains of social relationships and environment of WHOQOL had a correlation with family empowerment function of FES (p˂0.01, p˂0.05). About brothers and sisters’ affective intervention of FAD correlated with self-esteem of KINDL (p˂0.05). Our results suggested each of these outcomes was intimately linked cyclically. And we discussed it is necessary to enhance family function, QOL, family empowerment totally. Therefore, it is required to build or improve the comprehensive care support system / empowerment system in community life, for the family rearing child with severe motor and intellectual disabilities at home, in Japan.

Reference Ozawa H et al, The Present Situation of Children with Psycho-Motor Disabilities and Their Parents. Brain & Development 39(4);279-282, 2007.

162 Oral Presentation

O-24

How a group-based anger-management parenting program changed mothers’ cognition, attitude and behavior

Hiromi Tobe and Yoko Emori

Maternity Nursing and Midwifery, Faculty of Medicine, University of Tsukuba

Background: Parenting can be very challenging since it requires much time, energy and pa- tience; while at the same time, parents get almost no training to fulfi ll this diffi cult duty. Many mothers rearing children claim that they get too angry with their children too often and express their anger in negative ways, and they feel guilty about it. Objective: This study aimed to examine how participating in a group-based anger-manage- ment parenting program changed mothers’ cognition of their anger, their attitude and their behavior toward their children. Methods: A group-based parenting program, applying both anger-management skills and par- enting skills, was conducted for 50 mothers. Each group consisted of 5-8 mothers who had at least one child aged 4-12 years and wanted to cope with their anger toward their children in better ways. Each group received three two-hour long programs. The trained anger-manage- ment facilitator with parenting experience led the program by giving lectures and supporting the participants by frankly discussing their problems, negative feelings and desires. At the sec- ond and the third program, the participants reported the changes they had experienced using the skills and knowledge they had obtained in the programs. Also an original questionnaire was used to examine how the mothers changed. Results: The following are the statements with which most mothers either agreed or strongly agreed: I have increased my knowledge and understanding of anger. I feel less guilty when I feel or express my anger. I can see my anger more objectively. I get angry with my child less often. I express my anger with harsh words less often. I have more realistic expectations to- ward my child. I try to focus on the things my child can do rather than the things he/she can’t do. I try not to worry too much about my child’s future. Conclusion: By participating in the group-based anger-management parenting program, mothers increased their knowledge and understanding of anger, eased their guilt, changed their perspective of the child, decreased the frequency of their anger and expressed their anger in more appropriate ways.

163 Poster Presentation

P-1

The effect of different soil utilizition on the RIP of 137Cs contaminated soil from northern Japan

Min Li1, Kenji Tamura2, Junko Takahashi2, and Yuichi Onda2

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

In the earthquake of Mar. 11st 2011, the explosion of Fukushima Dai-ichi NPP made the rounding environment contaminanted, Caesium-137 is the most important long-term contributor to environmental contamination because of the high release rate, and longer half life. The extent of radiocaesium retention in soil is important to quantify the risk of further foodchain contamination. Modelling how the caesium transfer from soil to plants and hence into the food chain is also a complicated work. Therefore, in the research the immobilization of Cs and the Radiocaesium Interception Potential have been focused on.Radiocaesium interception potential (RIP), which is introduced by Cremers et al. has proven to be a useful parameter to characterise the sorption of radiocaesium by soils, is an intrinsic soil parameter which can be used to categorize soils or minerals in terms of their capacity to selectively adsorb radiocaesium. In the research, the simpllifi ed experiment by J.Wauters was used. The RIP is defi ned as

RIP = [FES] KcFES( Cs + ) K + where [FES] is the sorption capacity for radiocaesium by the frayed edge sites (FES) of micaceous clay minerals and KFES (Cs+/K+) is the selectivity coeffi cient of the ion exchange Cs+/K+ . The objective of the research is analyze the effect of content of C, N and the soil type on the RIP, and the movement and migration of Cs in soil. For result: RIP of samples from Fukushima are 289.820~2150.915mmol/ kg; RIP of samples from Miyagi are 705.529~1104.083 mmol/ kg; RIP of samples from Ibaraki are 256.971~914.704 mmol/ kg the RIP in forest soil is higher than in farmland.

164 Poster Presentation

P-2

Function characterization of a second and novel mRNA capping apparatus in Trypanosoma brucei

Anna Ignatochkina and Kiong Ho

Infection Biology Section, Faculty of Medicine, University of Tsukuba

The 5’ end of kinetoplastid mRNA possesses a hypermethylated cap 4 structure, which is derived from standard m7GpppN with additional methylations at seven sites within the fi rst four nucleosides on the spliced leader RNA by trans splicing. Earlier studies indicated that Trypanosoma brucei encodes two separate capping apparatus, exemplifi ed by guanylyltransferases TbCgm1 and TbCe1. The TbCgm1 was shown to be expressed in the nucleus and was responsible for capping of the spliced leader RNA. In contrast TbCe1 was predominantly expressed in the cytoplasm, but the biological function and it`s RNA target is not known. The aim of this project is to understand the function of TbCe1 in Trypanosoma RNA metabolism. Our results demonstrate that TbCe1 is a bifunctional capping enzyme with an N-terminal phosphotransferase and C-terminal guanylyltransferase activities, and may function to regulate the abundance of translatable mRNA in the cytoplasm. This study may lead to a new paradigms in cellular mRNA regulation.

165 Poster Presentation

P-3

The genetic compatibility among infl uenza virus polymerase subunits for the generation of reassortant viruses

Yoshimi Harada1,3, Kyosuke Nagata2, and Atsushi Kawaguchi1,2,3

1Department of Infection Biology, 2Faculty of Medicine and 3Graduate School of Comprehensive Human Sciences, University of Tsukuba

The genome of infl uenza virus consists of eight-segmented and different viral protein-coded RNAs of negative polarity. When different infl uenza strains coincidentally infect a single cell, new type of viruses will appear by reassortment of segmented genomes. Theoretically, 256 reassorted genotypes can be generated from two distinct strains, but the infectious reassortants hardly emerge in nature, suggesting that the compatibility between viral genomes or/and encoded viral proteins regulates the product effi ciency of infectious reassortants. However, the molecular mechanism responsible for this compatibility is largely unknown. Here we found that genetic interaction between viral polymerase subunits is important for the production of reassortant viruses. We generated single gene reassortants between A/Puerto Rico/8/34 (H1N1) (PR8) and A/Hong Kong/483/97 (H5N1) (HK483) by reverse genetics system. Among them, reassortant viruses possessing genes encoding PB2 and PA viral polymerase subunits from HK483 (designated HK483-PB2 and HK483-PA, respectively) with other PR8 genes were hardly recovered. The viral polymerase consisting of PB1, PB2, and PA subunits is required for the viral genome replication and transcription, and the replicated viral genomes are assembled into viral ribonucleoprotein (vRNP) by interacting with viral polymerase complexes and nucleoprotein. Since HK483-PB2 with PR8 other subunits did not have the RNA synthesis activity, it is likely that the genetic compatibility among viral polymerase subunits is important for the viral polymerase activity. In contrast, the RNA synthesis activity of HK483-PA with PR8 other subunits was unaffected, suggesting that the genetic compatibility among viral polymerase subunits is also responsible for a post replicational process(es). To address this, we examined the intracellular localization of vRNP. After the nuclear export, vRNP with HK483-PA and PR8 other subunits was found in unknown cytoplasmic granules at juxta- nuclear regions. Taken altogether, it is possible that the viral polymerase complex is involved in the intracellular transport of vRNP to the assembly site of viral particles beneath the plasma membrane.

166 Poster Presentation

P-4

A Cullin-related protein regulates posttranslational modifi cation of PML

Tomomi Fukuda, Yu Kigoshi, and Tomoki Chiba

Graduate School of Life and Environmental Sciences, University of Tsukuba

Posttranslational modifi cation of proteins is involved in diverse phenomena. SUMOylation is a posttranslational modifi cation that regulates various cellular processes, including transcription, cell-cycle progression and DNA damage repair. PML is known to be SUMOylated and also has a SUMO interacting motif, both important for PML Nuclear Bodies (PML-NBs) formation. PML-NBs are (de)SUMOylation platforms where SUMO is coupled to or detached from its target protein leading to regulation of nuclear activities. Furthermore, SUMO2 modifi cation of PML leads to its ubiquitination by ubiquitin E3 ligase RNF4 in the PML-NBs and degradation by the proteasome. Recently, we revealed that a Cullin-related protein iCul inhibits the ubiquitination activity of Cullin3-based E3 ligases. In addition, recent proteomics analysis revealed SUMO2 as iCul interaction partner. Therefore, we hypothesised that iCul may be associated with protein SUMOylation. Here, we demonstrate that iCul interacts with PML and SUMO E2 enzyme Ubc9, and that iCul inhibits SUMOylation and ubiquitination of PML. Immunocytochemical analysis showed that both iCul and Ubc9 accumulate to PML-NBs by PML overexpression. These results suggest that iCul negatively regulates posttranslational modifi cation of PML at PML-NBs.

167 Poster Presentation

P-5

A novel transcriptional regulation of steroid hormone biosynthesis in Drosophila melanogaster

Tatsuya Komura-Kawa1, Sora Enya1, Tetsuro Shinoda1, Michael B. O’Connor3, and Ryusuke Niwa1,4

1Graduate School of Life and Environmental Sciences, University of Tsukuba, Japan 2Division of Insect Science, National Institute of Agrobiological Sciences, Japan 3Department of Genetics, Cell Biology and Development, University of Minnesota, USA 4PRESTO, JST, Japan

In insects, molting and metamorphosis are regulated by the steroid hormones called ecdysteroids, such as ecdysone and its derivative 20-hydroxyecdysone (20E). During post- embryonic development, ecdysteroids are synthesized from dietary cholesterol via a series of hydroxylation and oxidation steps in the prothoracic gland (PG). The steroidogenic function of the PG is defi ned by the restricted expression of ecdysteroidogenic enzyme genes. The precise dynamics of ecdysteroid titers and the cell-type specifi c pattern imply a tight transcriptional regulation of these enzymes in the PG. However, the PG specifi c transcriptional regulatory networks have not yet been fully elucidated. In this presentation, we report a gene tentatively called ouib, encoding a C2H2-type Zn-fi nger transcription factor, plays an essential role in controlling expression of the ecdysteroidogenic enzyme gene in the fruit fl y Drosophila melanogaster. ouib is predominantly expressed in the PG. A PG-specifi c RNAi knock-down for ouib resulted in larval developmental arrest, which was rescued by administering 20E. Interestingly, ouib RNAi animals exhibited a drastic reduction of expression level of one but not any other ecdysteroidogenic enzyme genes examined so far. Moreover, we established ouib mutant lines by CRISPR/Cas9 system, which showed similar phenotypes to ouib RNAi animals. A luciferase-reporter assay revealed that Ouib protein indeed had transcriptional activity for the specifi c ecdysteroidogenic enzyme gene. Using this assay system, we identifi ed a specifi c enhancer element necessary for the transcriptional regulatory activity of Ouib. Our study illustrates that a certain transcription factor is required for the very small subset of steroidogenic gene(s) essential for specifi c catalytic step(s), providing a novel insight into the regulatory mechanism of steroid hormone biosynthesis.

168 Poster Presentation

P-6

The budding yeast AMPK ortholog Snf1 negatively regulates endoplasmic reticulum stress response

Yuto Masuda, Mizuno Tomoaki, and Kenji Irie

Department of Molecular Cell Biology, Graduate School of Comprehensive Human Sciences, University of Tsukuba

AMP-activated protein kinase (AMPK) is highly conserved in eukaryotes and important for cellular energy homeostasis. The budding yeast ortholog of AMPK, Snf1, is required primarily for the adaptation of yeast cells to glucose limitation and for growth on carbon sources that are less preferred than glucose. Snf1 is also involved in responses to other environmental stresses, including heat shock, alkaline pH and oxidative stress. However, it remains unknown whether Snf1 functions in endoplasmic reticulum (ER) stress response. In this study, we found that Snf1 is involved in ER stress response. The snf1Δ mutation exhibits resistance to ER stress. This snf1Δ mutant phenotype is rescued by expression of wild-type Snf1, but not by expression of a kinase dead form of Snf1, suggesting that Snf1 negatively regulates ER stress response in a manner dependent on its kinase activity. Previous studies demonstrated that Snf1 activity is regulated by its phosphorylation: the phosphorylated form is active; the dephosphorylated form is inactive. Therefore, we examined the effect of ER stress on Snf1 phosphorylation and found that the phosphorylated form of Snf1 is upregulated by ER stress. Taken together, these results suggest that ER stress activates Snf1, which, in turn, negatively regulates ER stress response.

169 Poster Presentation

P-7

Challenges for sustainable tomato production: Isolation of a novel tomato mutant with enhanced fruit set effi ciency and candidate gene approaches by Next Generation Sequencing

Hitomi Takei, Yoshihito Shinozaki, Hiroshi Ezura, and Tohru Ariizumi

College of Agrobiological Resource Sciences, University of Tsukuba

Tomato (Solanum lycopersicum) belongs to the fl owering plant family Solanaceae that includes many important vegetable crops. Although tomato is cultivated worldwide, its production strongly depends on the successful fruit set, which is the developmental transition from ovary to fruit after pollination and fertilization. However, fruit set is easily hindered by environmental conditions such as high/low temperatures. To improve the effi ciency of fruit set under the severe conditions, farmers must artifi cially induce pollination by application of plant hormones or with insect vectors, although such artifi cial pollination systems require for many costs and working time. Meanwhile, parthenocarpy, a fruit formation in the absence of pollination and fertilization, is an attractive trait to relieve farmers from artifi cial pollination. To date, several genetic loci inducing parthenocarpy, known as pat, have been identifi ed, but they often carry undesirable fruit traits (e.g. over-softening, malformation of leaf and fruit etc.) simultaneously. Therefore development of new parthenocarpy tomato varieties without these undesirable traits is an important subject for agriculture. The aim of this research is to identify the responsible gene for parthenocarpy by using map-based cloning and next generation sequencing (NGS). To isolate novel gene associate with parthenocarpy, we have been developing mutagenized populations of tomato in variety ‘Micro-Tom’ and successfully isolated a mutant that exhibits effi cient parthenocarpy. By the map-based cloning, the genetic locus responsible for mutant phenotype was refi ned to ~2.0 Mbp in physical length which spans 205 open reading frames (ORFs). Furthermore NGS analysis revealed DNA substitutions or deletions within several ORFs. Here we present the evidence that one mutation is tightly associated with mutant phenotype. Future work will determine whether this mutation is responsible for the mutant phenotype by genetic complementation experiments. Our research would provide a great potential for agriculture to produce fruits easily and effi ciently, result in improved yield of tomato.

170 Poster Presentation

P-8

Construction of genetic analysis available multidrug sensitive yeast strain by both the disruption of drug effl ux system and the conditional repression of membrane barrier system

Takumi Chinen1, Yoko Nagumo2, and Takeo Usui2

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

The budding yeast Saccharomyces cerevisiae, is a useful tool for chemical biology studies, including drug screening, target identifi cation, and speculation, and the verifi cation of bioactive compounds. However, the high-level drug resistance of S. cerevisiae makes analyses of compounds diffi cult. There are two systems conferring multidrug resistance in S. cerevisiae, one is the drug effl ux system, and the o ther is the permeability barrier system. The drug effl ux system is composed of ABC transporters that export xenotoxic compounds to outside of the cells or inside of vacuole. The major factor of the permeability barrier system is ergosterol in the yeast plasma membrane. These mechanisms confer drug resistance against different group of drugs, thus to make yeast sensitive to several compounds, the disruption of ABC transporters and ergosterol biosynthetic genes (ERG genes, e.g., ERG6) are required. However, the gene disruption involved in ergosterol biosynthesis, especially erg6 gene, decreases the transformation, mating and sporulation effi ciencies, which are required for genetic analyses. In this study, we constructed 12geneΔ0HSR-iERG6 by introduce the ERG6 conditional expression system based on GAL1 promoter into 12geneΔ0HSR, a strain lacks drug effl ux system by disruption of ABC transporters on the plasma membrane (T. Chinen et al., Biosci. Biotechnol. Biochem., 75, 1588-1593 (2011)). 12geneΔ0HSR-iERG6 showed improved drug sensitivity to several compounds under glucose condition, and its drug sensitivity spectrum was resembled with that of erg6 disruptant of 12geneΔ0HSR. These results suggest that 12geneΔ0HSR-iERG6 lacks both the drug effl ux system and the membrane barrier system required for multidrug resistance. Moreover, 12geneΔ0HSR-iERG6 showed suffi cient effi ciencies of transformation, mating, and sporulation for genetic analysis under the galactose condition. Therefore, 12geneΔ0HSR-iERG6 is a useful tool for chemical biology studies including the drug screening, target identifi cation (T. Chinen et al., J. Gen. Appl. Microbiol., in press).

171 Poster Presentation

P-9

Involvement of the small GTPase Arf6 in PDGF-induced dorsal ruffl ing

Taito Miyachi, Tsunaki Hongu, Yuji Funakoshi, and Yasunori Kanaho

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

Activation of receptor tyrosine kinases induces the dynamic rearrangement of plasma membrane structure, such as ruffl e formation, which is mediated by the reorganization of actin cytoskeleton at plasma membrane. The ruffl ing membranes are subdivided into two independent types. One is the peripheral ruffl e, which is upward-bending structures of the cell membrane at the leading edge of cells and plays crucial roles in cell adhesion and directed cell motility. Another is the dorsal ruffl e, which is characterized by their unique appearance on the dorsal surface of cells as a ring-shaped structures and is essential for receptor internalization and cell migration. Although formation of both types of ruffl es require the reorganization of actin cytoskeleton, precise regulatory mechanism has not yet been clarifi ed. The small GTPase ADP-ribosylation factor 6 (Arf6) exclusively localizes to the plasma membrane and endosomal compartments, and plays important roles in actin cytoskeleton reorganization. We have previously found that Arf6 regulates the growth factor-induced peripheral ruffl e formation. However, the involvement of Arf6 in dorsal ruffl e formation has not yet been clarifi ed. Here, we show that Arf6 also regulates dorsal ruffl e formation. In response to the platelet-derived growth factor (PDGF) stimulation, Arf6 was activated and localized at dorsal ruffl e membrane in mouse embryonic fi broblasts. In addition, genetic ablation of Arf6 suppressed PDGF-induced dorsal ruffl e formation. These results demonstrate the critical role of Arf6 in tyrosine kinase receptor-mediated membrane ruffl e formation.

172 Poster Presentation

P-10

Tumor-infi ltrating CD8 T lymphocytes are decreased in Phospholipase D2 knockout mice

Ngo Thai Bich Van, Takanobu Sato, 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 a membrane phospholipid phosphatidylcholine (PC) to produce choline and the lipid messenger phosphatidic acid (PA). Two isozymes, PLD1 and PLD2 have been identifi ed in mammalian cells. Through the production of PA, both PLD1 and PLD2 are involved in various cellular functions such as vesicular traffi cking, intracellular se- cretory response, cell motility, and cell proliferation. Recently, it has been reported in a mouse model that PLD1 is involved in tumor growth through the promotion of tumor angiogenesis. PLD2 is also implicated in tumor growth and metastasis, however, the mechanism how PLD2 is involved in cancer progression remains to be elucidated. Here, by using PLD2-knock out (KO) mice, we demonstrate that PLD2 suppresses tumor growth through the regulation of T- cell functions. To investigate the function of PLD2 in tumor growth, we subcutaneously transplanted B16 melanoma cells into WT and PLD2-KO mice. Unlike the previous report on PLD1-KO mice, the tumor growth of B16 melanoma cells was signifi cantly enhanced in PLD2-KO mice, indicating that PLD2 has a suppressive function in tumorigenesis. When we analyzed sections of the tumors, the number of apoptotic cells in the tumor was decreased in PLD2-KO mice, whereas tumor angiogenesis was not affected. These results indicate that enhancement of tumor growth in PLD2-KO mice is attributable to inhibition of cell apoptosis. Since the im- mune system is known to affect survival of cancer cells, we next examined infi ltration of im- mune cells into the tumor. The number of CD8-positive cytotoxic T lymphocytes in the tumor was signifi cantly decreased in PLD2-KO mice, whereas the number of CD4-positive helper T lymphocytes was not changed. In addition, CD8-positive but not CD4-positive T lymphocytes were reduced in spleen of PLD2-KO mice. Furthermore, the directional migration of activated CD8-positive T cells towards chemokine CXCL12 (50 ng/ml) in vitro was inhibited in the cells lacking PLD2. Taken together, these results indicate that PLD2 plays a key role in the regula- tion of CD8-positive T lymphocyte that might suppress tumorigenesis.

173 Poster Presentation

P-11

Role of THG-1 in tumor angiogenesis through stabilization of HIF-1α in normoxic condition

Ling Zheng, Hiroyuki Suzuki, and Mitsuyasu Kato

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

THG-1/Tsc22D4 is one of Tsc22 family member. We found that THG-1 is localized in the basal layer of normal squamous epithelium, and is ubiquitously expressed in squamous cell carcinoma cells. THG-1 is phosphorylated by EGF signaling and promotes cell proliferation, invasion and tumorigenesis. Our previous data showed that THG-1 knockdown reduced not only tumor sizes but also blood vessel densities compared with THG-1 expressing control tumors. It suggested that THG-1 may be involved in tumor angiogenesis. Interactome analysis suggested that THG-1 binds to prolyl hydroxylase domain-containing protein 2 (PHD2), which regulates the stability of a transcription factor hypoxia inducible factor-1α (HIF-1α). Hypoxia is a condition that is known to drive angiogenesis in tumors. HIF-1α is a transcription factor that induces vascular endothelial cell growth factor. Our data showed that phosphorylated THG-1 interact with PHD2 and stabilize HIF-1α. These results indicated that THG-1 promotes angiogenesis by binding to PHD2 and regulating HIF-1α stability even in the normoxic condition.

174 Poster Presentation

P-12

Dormant cancer cells have high reserved antioxidant capacity that may promote their radioresistance

Kazuya Ito1, Takashi Moritake2, Lue Sun1, Kenshi Suzuki1, Ariungerel Gerelchuluun1, and Koji Tsuboi1

1Radiation biology section, University of Tsukuba 2Medical science for occupational and environmental health, University of Occupational and Environmental Health

[Background] It is known that dormant cancer cells are radioresisitant, however, the precise mechanisms of their radioresistance have not been elucidated yet. As reactive oxygen species (ROS) play an important role in cellular response to ionizing radiation, we compared “antioxidant capacity” of dormant and growing cells in this study. [Materials & Methods] Human medulloblastoma cell lines ONS-76 were harvested at 48, 72 and 96 hours after seeding (1.0 × 106 cells in each 75 cm2 Flask). The cells at 48 hours were at the exponentially growing phase and those at 72 and 96 hours were in dormancy. In each sample, levels of intracellular ROS were measured by fl owcytometry using 2’, 7’-Dichlorodihydrofl uorescin diacetate (DCFH-DA). Also, antioxidant capacity was evaluated by the electron spin resonance (ESR) method using 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (Tempol). The ESR signals were measured every 15 minutes for 2 hours to calculate the reaction rate constant (k [min-1] ) . [Results] DCF assay showed that the amounts of ROS in dormant cells (72 and 96 hours) were lower than those in growing cells (48 hour) and they were not increase even after 8 Gy of X-ray irradiation. Although antioxidant capacity of dormant cells (k = 1.4 × 10-2 and 1.3 × 10 -2 for 72 h and 96 h, respectively) was smaller than that in growing cells (k = 1.7 × 10-2 for 48 h), they became almost the same level (k ~− 1.9 × 10-2) 4 hours after irradiation. [Conclusions] As the difference of k-values between pre- and post-irradiation indicates potentially reserved antioxidant capacity of cells, larger difference of k-values in dormant cells as compared to growing cells may explain the property of radioresistance of dormant cells. (prepared for submission to Free radic. Boil. Med.)

175 Poster Presentation

P-13

Non-invasive in vivo near-infrared fl uorescent imaging of tumors with iRFP

Shota Sakaguchi1,2, Junko Tanaka1,3, Yuka Sugiyama1, Tomoki Sakasai1,2, Takanobu Kuroyama1,2, and Yoshihiro Miwa1,3

1Department of Molecular Pharmacology, University of Tsukuba 2Graduate School of Comprehensive Human Sciences, University of Tsukuba 3Faculty of Medicine, University of Tsukuba

An optimal fl uorescent protein for in vivo imaging should have excitation and emission maxima within a NIR region from 650 nm to 900 nm because mammalian tissue has the lowest absorbance in this region. For 1~2 cm-thick mouse body, non-invasive whole-body fl uorescent imaging is possible within the NIR region (Jobsis, F.F., Sc ience 198, 1264-1267, 1977). Recently, Phytochrome-based near-infrared fl uorescent protein (iRFP) was engineered (G.S. Filonov, et al., Nat Biotech.29, 757-761, 2011). In this study, we have demonstrated fl uorescence imaging of mice tumor with iRFP. First, we established iRFP-expressing Lewis Lung Carcinoma (LLC) cell line derived from C57BL/6. iRFP-expressing LLC cells were injected via the tail vein of BALB/c-nu/nu. Then, we monitored metastases into lungs non-invasively by using an In Vivo Imaging System (IVIS Spectrum) and an X-ray CT. NIR fl uorescence signal from lungs were detected with both two-dimensional and three-dimensional imaging. Next, iRFP- expressing LLC cells and wild-type (WT) LLC cells were injected s.c. to three kinds of mice : C57BL/6 albino, C57BL/6 iRFP Tg mice expressing iRFP in whole-body, and BALB/c-nu/nu. Then, we monitored the growth of the tumors and NIR fl uorescence. In C57BL/6 albino mice, WT-LLC cells formed tumors rapidly after injection. However, iRFP-expressing LLC cells formed tumors slowly and NIR fl uorescence signal was disappeared in most of tumors. On the other hand, in iRFP Tg and BALB/c-nu/nu mice, iRFP-expressing LLC cells rapidly formed tumors like WT-LLC cells and kept high intensity of NIR fl uorescence. In conclusion, NIR fl uorescence from iRFP-expressing tumors was detected non-invasively in internal organs of living mice. However, iRFP-expressing cells could be immunologically rejected in allogeneic C57BL/6 mice. Now, we are investigating the mechanism of this rejection and searching ways to overcome this rejection to establish further applications of in vivo imaging.

176 Poster Presentation

P-14

Chondrodysplasia in mice lacking both chondroitin sulfate N-acetylgalactosaminyltransferase-1 and -2

Miki Shimbo1, Takashi Sato2, Kozue Hagiwara2, Hisashi Narimatsu2, Satoru Takahashi1, and Takashi Kudo1

1Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba 2Glycomedicine Technology Research Center, AIST

Chondroitin sulfate (CS), a sulfated glycosaminoglycan chain that consists of repeating disaccharide units, is a main component of extracellular matrix (ECM) in cartilage. Although CS is widely known to play an important structural role in cartilage function, its role in chondral development is less known. To assess the role of CS in chondral development, we previously generated mice lacking chondroitin sulfate N-acetylgalactosaminyltransferase-1 (Csgalnact-1), one of the CS synthases predicted to initiate CS chain synthesis. Our results revealed that Csgalnact-1 null mice exhibit slight dwarfi sm. However, the amounts of CS in Csgalnact-1 null cartilage still remained about 50% that of wild-type mice, indicating that other CS synthases also contribute to CS chain initiation. Based on the previous studies showing the initiation activity of Csgalnact-2 in vitro, here, we generated Csgalnact-1 and -2 double null mice. The double null mice died shortly after birth due to respiratory failure and they showed slightly shorter length of long bones than that of wild-type. To examine the role of CS in postnatal chondral development, we then generated a cartilage-specifi c Csgalnact-1 and -2 deleted mouse (Col2-t1::t2). Most Col2-t1::t2 mice died shortly after birth due to respiratory failure, but a few newborn mice were survived. Interestingly, although the Col2-t1::t2 mice had no difference in body weights at the day of birth, they developed a severe dwarfi sm showing almost 50% reduction in body weight compared with that of wild-type. Histological analysis of growth plate in Col2-t1::t2 proximal tibial epiphysial cartilage at P7 and P14 revealed a chondrodysplasia characterized by reduction of the glycosaminoglycan content in ECM, an abnormal shape of chondrocytes, and disorganization of the growth plate. These results indicate that the CS synthesized by both Csgalnact-1 and -2 plays a critical role in postnatal endochondral bone formation.

177 Poster Presentation

P-15

MafB regulates macrophage-osteoclast progenitor cell function

Zeinab Kosibaty1,2, Michito Hamada1,2, Kyoko Sawaguchi1, and Satoru Takahashi1

1Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba 2International Institute for Integrative Sleep Medicine (WPI-IIIS)

Osteoclasts are multinucleated cells of hematopoietic origin, which are unique in their ability to resorb bone. Receptor activator of nuclear factor kappaB (RANK) and its ligand RANKL is essential for osteoclast differentiation and survival. Osteoclasts are derived from myeloid lineage cells that also required macrophage colony-stimulating factor (M-CSF). Previous studies showed that osteoclasts and macrophages share a common hematopoietic progenitor defi ned by CD11b- CD3- B220- CD115+ cells in bone marrow (BM) o r spleen. However, it is largely unknown which mechanisms decide their fate differentiation to osteoclast. MafB is a member of the large Maf family of transcription factors. MafB is highly expressed in monocytes and macrophages. It has been reported that MafB inhibits osteoclast differentiation. In human, mutations in the amino-terminal transcriptional activation domain of MAFB have been identifi ed in Multicentric Carpotarsal Osteolysis (MCTO) patients. However, the molecular mechanism of MafB in osteoclastgenesis is still unclear. Here, we analyzed the function of MafB in myeloid linage, including macrophage and osteoclast. Numbers of macrophage colonies from Mafb-/- fetal liver cells were signifi cantly increased. Moreover, in Mafb-/- BM cells, number of colonies induced by M-CSF from sorted fraction lin-c-kit-sca-1- were dramatically increased. GFP was expressed in lin-c-kit- sca-1- CD115+ in Mafb-/- (GFP knock in) mice. We suggest that abnormal fraction that sensitive to M-CSF is caused to increase osteoclast. Whereas we conducted osteoclast formation by M-CSF and RANKL using Mafb defi cient bone marrow and fetal liver cells. The result was showed abnormal osteoclast differentiation in Mafb-/- mice in both BM and fetal liver cells. These results indicate that MafB regulates osteoclast differentiation in specifi c myeloid cells lin-c-kit- sca-1- CD115+. Our results revealed that MafB has a critical role in osteoclast differentiation through specifi c myeloid cells lin-c-kit-sca-1- CD115+. This study will help to clarify the molecular mechanism of bone diseases.

178 Poster Presentation

P-16

MafK overexpression impairs pancreatic β-cells development in vivo

Ahmed Abdellatif, Hisashi Oishi, Takahiro Itagaki, and Satoru Takahashi

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

The pancreatic β-cells are the only cells that can produce insulin to maintain normal glycaemia. Defi ciency of insulin can cause a chronic metabolic disorder, diabetes mellitus (DM). The MAF family of transcription factor, which is a member of the bZip transcription factors, is homologs of v-Maf, the oncogenic component of the avian retrovirus AS42. It is subdivided into two groups, small and large MAF proteins. MAFA is a member of the large MAF family, which has been shown to be involved in insulin gene transcription, and Mafa knockout (KO) mice developed DM around 8 weeks of age. In addition, β-cells specifi c overexpression ofMafk , which is a member of small MAF group, in a Mafa knockout background has developed more severe DM compared to the Mafa KO mice. The aim of the current work is to study the effect of specifi c Mafk overexpression in pancreatic β-cells of mouse embryos. The developing islets of the transgenic embryos appeared disorganized with a reduction in the total insulin+ cell numbers at both E15.5 and E18.5 compared to control embryos. Moreover, the total insulin content signifi cantly decreased in transgenic embryos (WT; 5.6±0.59 ng vs. Tg; 1.1±0.09 ng (E15.5), WT; 13.4±0.48 ng vs. Tg; 10.02±0.48 ng (E18.5)). The examination of gene expression profi les by quantitative real time PCR revealed that both Ins1 and Ins2 genes were signifi cantly decreased. As well several genes related to β-cell function including Slc30A8, Npy, and G6pc2 showed reduced expression levels. On the other hand, both beta and alpha cells transcription factors like Pax4, Nkx2.2, Arx, and Mafb were found increased; indicating that compensatory mechanisms of these cells might be mediated by Mafk overexpression. Lastly, immunohistochemical staining using Ki67 antibody showed lower ratio of proliferating β-cells in the transgenic embryos (4.2% vs. 1% and 14.3% vs. 3% at E15.5 and E18.5 respectively). Our results suggest that Mafk overexpression impair β-cell development in embryos. Understanding factors that govern normal β-cell development is fundamental for revealing the mechanisms of their failure in disease conditions.

179 Poster Presentation

P-17

The role of large maf transcription factors in the β-like cell conversion from mouse liver

Yunshin Jung, Hisashi Oishi, Tokio Katsumata, Pei-Han Tai, Ryusuke Koshida, and Satoru Takahashi

Anatomy and Embryology Laboratory Animal Resource Center, Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan

Recent studies have shown that MAFB and MAFA have their distinctive roles on β-cell development and maturation, respectively. However, what causes the discrepancy in β-cell is not clearly explained yet. Their different gene expression timing could be one reason; Mafb expressed before birth and Mafa after birth. Our aim is to examine the functional difference between these closely related genes in β-cells using an in vivo mouse model that are designed for β-like cell production, MIP-luc reporter mouse. We monitored the insulin transcriptional activity using bioluminescence emitted from the liver of insulin promoter-luciferase transgenic mice upon gene transfers. Adenoviral gene transfers of Pdx1/Neurod/Mafa (PDA) and Pdx1/ Neurod/Mafb (PDB) combinations generated intense luminescence from the liver with the peak emission 3 days after transduction and lasted more than a week. The signal intensities of PDA and PDB were comparable. However, PDA not PDB gene transfer resulted in signifi cant luminescence on day 10, suggesting that Mafa has a more sustainable role on insulin gene activation than Mafb. PDA gene transfer induced several gene expressions necessary for glucose sensing and insulin secretion in the liver on day 9. However, glucose tolerance test and liver perfusion experiment showed that induced β-like cells did not respond to high glucose concentration. These results suggest that Mafa has markedly intense and sustainable role on β-like cell production in comparison with Mafb.

180 Poster Presentation

P-18

NPM1 functions as a subunit of enhanceosome for NF-κB-mediated transcription

Jian-Huang Lin1,2, Mitsuyasu Kato1,3,4, Kyosuke Nagata4, and Mitsuru Okuwaki1,2,4

1School of Integrative and Global Majors, University of Tsukuba 2Department of Infection Biology, University of Tsukuba 3Department of Experimental Pathology, University of Tsukuba 4Faculty of Medicine, University of Tsukuba

Nucleophosmin/NPM1, a nucleolar protein that shuttles continuously between the nucleus and the cytoplasm functions as a histone chaperone and plays important roles in cell growth and proliferation. Being over-expressed in cancer cells compared with normal cells, NPM1 has been thought to be involved in oncogenesis, but it is still not clear how it exerts its oncogenic role. In this study, we found that in the nucleus NPM1 interacts with NF-κB, a transcription factor that plays important roles in cancer development and progression. Activation of NF-κB by treatment of TNF-α enhanced the interaction with NPM1 in the nucleus. Interaction domain analyses revealed that NPM1 interacts with the N-terminal Rel homology domain of NF-κB p65 which contains its DNA binding domain and its inhibitory protein IκBα binding domain, indicating that NPM1 might affect the DNA binding activity of NF-κB. Knockdown of NPM1 impaired the NF-κB transactivation activity and NF-κB-mediated target gene expression. In addition, preliminary data indicated that TNF-α stimulation caused the recruitment of not only NF-κB but also NPM1 to the NF-κB target gene promoters. This suggests that NPM1 is a critical positive regulator of NF-κB-dependent gene expressions. Furthermore, there is a strong correlation found between the expression of NPM1 and the activated NF-κB p65 in colon tumor tissue, suggesting that NPM1 regulates NF-κB in vivo. This study provides a novel clue into the molecular mechanism by which NPM1 exerts its oncogenic role through the crosstalk with the NF-κB pathway.

181 Poster Presentation

P-19

Involvement of oviductal peristalsis in fertilization of the mouse

Yu Ishikawa1,2, Tomoyuki Usui2, Misuzu Yamashita2, and Tadashi Baba2

1Ph.D. Program in Human Biology, School of Integrative and Global Majors, University of Tsukuba, Japan 2Graduate School of Life and Environmental Science, University of Tsukuba, Japan

Fusion between two gametes, sperm and oocyte, is one of the most important events in fertilization. Ejaculated sperm migrate from the uterus to oviduct in the female reproductive tract, and fertilize the oocytes at the oviductal ampulla. Recently, sperm have been reported to recognize a high-viscosity fl uid fl ow in the oviduct, suggesting that sperm are guided by rheotaxis to reach the oocytes. Indeed, sperm exhibit the ability to swim against the fl uid fl ow. Since peristaltic and antiperistaltic waves in the oviduct walls is thought to generate the fl uid fl ow directed to the isthmus in the oviduct, it is reasonable to consider that oviductal peristalsis plays a key role in pumping sperm up to the ampulla. In this study, we have focused on migration of sperm through the female reproductive tract under the control of oviductal peristalsis. When prifi nium bromide (padrin), a well-known inhibitor of intestinal peristalsis, was administrated to mice, oviductal peristalsis was also prevented. The rate of fertilization by artifi cial insemination was gradually decreased by administration of padrin in a dose- dependent manner. As compared with the control group, the number of sperm reached the ampulla was signifi cantly decreased by padrin administration. Moreover, sperm were barely capable of gaining access to the oocytes in the padrin-administrated mice. These results suggest that the fl uid fl ow generated by ovidutal peristalsis is crucial for fertilization in vivo.

182 Poster Presentation

P-20

Identifi cation and characterization of human CD300H, the eighth member of the CD300-family receptors

Kouta Niizuma1,3, Satoko Tahara-Hanaoka1,4,5, Emiko Noguchi2,5, and Akira Shibuya1,4,5

1Department of Immunology and 2Department of Medical Genetics, Faculty of Medicine, 3Ph.D. Program in Human Biology, 4Center for TARA, University of Tsukuba, Japan 5CREST, Japan Science and Technology Agency

CD300 family molecules, which are encoded by a multigene family consisting of seven genes on a segment of chromosome 17 in human, are expressed on myeloid lineage cells and mediate either activating or inhibitory signals. Here, we have identifi ed a previously un- annotated gene located in the CD300 gene cluster and termed it as CD300H. CD300H has a short cytoplasmic tail and associates with an ITAM-containing adaptor, DAP12. A newly generated monoclonal antibody (mAb) against CD300H (TX93) detected CD300H expression on CD16+ monocytes and myeloid dendritic cells. To clarify the function of CD300H, we p u r i fi e d C D 1 6 + monocytes and stimulated them with TX93 mAb, resulting in production of proinfl ammatory cytokines and chemokines for neutrophils attraction. Interestingly, CD300H expression was variable among individuals; it can be classifi ed as “high-,” “moderate-,” and “no-” expression group as defi ned by fl ow cytometry analyses. Genomic sequence analysis revealed the existence of a single-nucleotide mutation, rs905709 (G→A), at splice donor site in exon 1, which is a leading cause of these individual differences in CD300H expression. The international HapMap project database demonstrated that 16.7% of Japanese carry A/A genotype (no-expression). Together, these results suggest CD300H may play an important role in regulation of infl ammatory responses in certain population who carry G/G or G/A genotype of CD300H.

183 Poster Presentation

P-21

DNAM-1 (CD226) plays an important role in antigen presentation by small peritoneal macrophages

Eri Takenaka1,3, Akira Shibuya1,2,4, and Kazuko Shibuya1

1Department of Immunology, Faculty of Medicine, 2Life Science Center of Tsukuba Advanced Research Alliance, University of Tsukuba 3Japan Society for the Promotion of Science 4Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency

Recent reports have revealed two distinct subsets of mouse peritoneal macrophages (CD11bhi F4/80hi large peritoneal macrophages (LPMs) and CD11b+ F4/80lo small peritoneal macrophages (SPMs)) (Ghosn EE et al., PNAS. 2010). Although LPM is a classical macrophage subset, the functional characteristics of SPMs remain unclear. We found that SPM expressed cd226 gene, which encodes an activating receptor DNAM-1 expressed on T cells and NK cells, 58-fold higher than did LPMs, based on the microarray data of Immunological genome project (Heng TS et al., Nat Immunol. 2008). In fact, DNAM-1 protein was strongly expressed on SPMs, but not on LPMs, suggesting that DNAM-1 may contribute to the function of SPMs. When we compared the percentages and cell number of SPMs between wild-type (WT) and DNAM-1-defi cient mice, these were not signifi cantly different in both mice, suggesting that DNAM-1 is not involved in the generation and maintenance of SPMs. Because SPMs express a higher level of MHC class II compared with LPMs, we investigated whether SPMs had antigen presenting ability and, if any, the role of DNAM-1 in the function by SPMs. We show that coculture of SPMs, but not LPMs, with naïve CD4+ T cells derived from OT-II mice in the presence of OVA peptide effectively induced CD4+ T cell priming, indicating that SPMs are antigen presenting cells. Furthermore, SPMs derived from DNAM-1-defi cient mice showed signifi cantly lower effect on induction of CD4+ T cell priming than those from WT mice, suggesting that DNAM-1 on SPMs is involved in antigen presentation. Taken together, we propose that SPMs are functionally distinct from LPMs, and DNAM-1 plays an important role in the antigen presentation by SPMs.

184 Poster Presentation

P-22

The role of CD300a (MAIR-I) in allergic airway infl ammation

Haruka Miki1,2, Chigusa Nakahashi-Oda1, Takayuki Sumida2, and Akira Shibuya1,3,4

1Department of Immunology, Faculty of Medicine, University of Tsukuba 2Department of Internal Medicine, Faculty of Medicine, University of Tsukuba 3Life Science Center of Tsukuba Advanced Research Alliance (TARA) 4Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency

CD300 family molecules are members of Ig super family bearing one Ig-like domain in the extracellular portion. One of the CD300 molecules, CD300a (MAIR-I), has a long cytoplasmic region containing the consensus immunoreceptor tyrosine-based inhibitory motif (ITIM) sequence and transmits an inhibitory signal. Recently we have reported that CD300a specifi cally binds to phosphatidylserine exposed on the outer leafl et of apoptotic cell plasma membrane. By crosslinking with monoclonal antibodies, CD300a inhibits mast cell or basophil degranulation in mice and human in vitro. However the physiological role of CD300a and its ligand has not been fully revealed. To explore the role of CD300a in allergic responses in vivo, we generated CD300a-defi cient mice and investigated ovalbumin (OVA)-induced widely used experimental asthma model. Eosinophil infi ltration in bronchoalveolar lavage (BAL) fl uid, serum IgE levels, and airway hyperreactivity index were signifi cantly decreased in CD300a-defi cient mice compared to WT mice. CD300a is highly expressed on monocyte-derived infl ammatory dendritic cells in the peritoneal cavity after injection of OVA antigen plus alum. In vitro experiments demonstrated that CD300a on infl ammatory dendritic cells induce robust Th2 responses. Blockade of CD300a interaction with phosphatidylserine by anti-CD300a neutralizing antibody resulted in inhibition of the development of allergic airway infl ammation. These results suggest that interaction of CD300a on infl ammatory dendritic cells with apoptotic cells play an important role in the development and pathogenesis of allergic airway infl ammation.

185 Poster Presentation

P-23

Somatic mosaic mutations in TET2 and DNMT3A in a case of peripheral T-cell lymphoma

Tran B. Nguyen1, Mamiko Sakata-Yanagimoto1,2,3, Rie Nakamoto-Matsubara1, and Shigeru Chiba1,2,3

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

[Backgrounds] Somatic mutations in DNMT3A and TET2 are frequently found in peripheral T-cell lymphomas (PTCLs). These mutations are found not only in tumor cell, but also in apparently normal blood cells. This has led to an idea that the cell origin of the DNMT3A and TET2 mutations may be hematopoietic stem cells (HSCs). However, origins of these mutations have not been elucidated. [Objective] We analyzed distribution of TET2/DNMT3A mutations in various tissues of a PTCL patient to estimate the origins of these mutations. [Method] Genomic DNA was collected from various tissues/cells of a 74 year-old PTCL patient and subjected to amplicon-based deep sequencing. [Results] CD4+PD1+ tumor cells purifi ed from peripheral blood (PB) showed mutations in DNMT3A and TET2 at allele frequencies of 50% and 47%, indicating that all circulating tumor cells had both mutations. The identical DNMT3A and TET2 mutations were detected in CD19+ B, CD4+PD1- T, and CD8+ T cells, and CD14+ monocytes in PB, as well as in PB derived colonies. Furthermore, these mutations were also identifi ed in genomic DNA collected from nail, indicating somatic mosaic mutations (SMMs), although the allele frequencies were less than 1%. [Discussion] This is the fi rst report describing SMMs in two tumor driver genes in lymphogenesis. Discordance between mutation allele frequencies between nail and blood cell DNA indicates growth advantage of mosaic cells after bone marrow establishment. In some cases, the origin of PTCL could be traced back to mosaic cells acquiring two major driver mutations, during early embryogenesis.

186 Poster Presentation

P-24

Association of leukocyte immunoglobulin-like receptor A3 (LILRA3) deletion polymorphism with systemic sclerosis

Yuki Hachiya1, Aya Kawasaki1, Takashi Matsushita2, Hiroshi Furukawa3, Shouhei Nagaoka4, Kota Shimada5, Shoji Sugii5, Takayuki Sumida6, Shigeto Tohma3, Minoru Hasegawa7, Manabu Fujimoto8, Shinichi Sato9, Kazuhiko Takehara2, and Naoyuki Tsuchiya1

1Molecular and Genetic Epidemiology, University of Tsukuba 2Department of Dermatology, Kanazawa University 3Clinical Research Center for Allergy and Rheumatology, Sagamihara Hospital, National Hospital Organization 4Department of Rheumatology, Minami Kyosai Hospital 5Department of Rheumatology, Tokyo Metropolitan Tama Medical Center 6Department of Internal Medicine, University of Tsukuba 7Department of Dermatology, University of Fukui 8Department of Dermatology, University of Tsukuba 9Department of Dermatology, University of Tokyo

Background: The leukocyte immunoglobulin-like receptors (LILRs) are a gene family located at 19q13.4. LILRs are expressed mainly in immune cells as transmembrane receptors, and some of LILRs have been shown to regulate immune cell activation. LILRA3 is the only secreted protein among LILRs, whose function remains unclear. Furthermore, LILRA3 has a 6.7-kb deletion polymorphism which lacks most of the coding region, and its frequency is especially high in the East Asian population (71.0% in the Japanese) (Hirayasu et al., 2006). Previous studies in European populations reported association of the deletion allele with multiple sclerosis (MS) (Koch et al., 2005) and Sjögren’s syndrome (SS) (Kabalak et al., 2009), while recent studies from China reported association of homozygous non-deletion genotype with rheumatoid arthritis (Du et al., 2014a), systemic lupus erythematosus (SLE) and SS (Du et al., 2014b). In this study, we examined whether LILRA3 deletion polymorphism is associated with systemic sclerosis (SSc) in a Japanese population. Methods: 377 Japanese patients with SSc and 867 healthy Japanese controls were examined. The LILRA3 deletion was genotyped by PCR-sequence specifi c primers. Results: We observed higher frequency of LILRA3 deletion in anti-topoisomerase 1 antibody positive (ATA+) SSc patients compared with healthy controls (P=0.012, OR=1.68). This association was not observed in anti-centromere antibody positive (ACA+) SSc. In the case- only analysis, the deletion allele frequency of ATA+ACA- SSc was signifi cantly increased when compared with ATA-ACA+ SSc (P=0.020, OR=1.77). Conclusion: Our study demonstrated the fi rst evidence for the association between the LILRA3 deletion and ATA+ SSc. The risk allele was in agreement with that of MS and SS in the German population, but was the opposite to that of RA and SLE in the Chinese population. This study supported the association of LILRA3 with genetic susceptibility to multiple autoimmune diseases, and its role requires further study.

187 Poster Presentation

P-25

Association of TRIM21 (RO52) polymorphisms with systemic lupus erythematosus in a Japanese population

Misaki Hidaka1, Aya Kawasaki1, Hiroshi Furukawa2, Yuya Kondo1, Satoshi Ito3, Isao Matsumoto1, Makio Kusaoi4, Hirofumi Amano4, Akiko Suda5, Keigo Setoguchi6, Tatsuo Nagai7, Kota Shimada8, Shoji Sugii8, Akira Okamoto9, Noriyuki Chiba10, Eiichi Suematsu11, Masao Katayama12, Akiko Okamoto13, Hajime Kono13, Shigeru Ohno14, Shunsei Hirohata7, Shouhei Nagaoka5, Yoshinari Takasaki4, Hiroshi Hashimoto15, Shigeto Tohma2, Takayuki Sumida1, and Naoyuki Tsuchiya1

1Faculty of Medicine, University of Tsukuba, 2Sagamihara Hospital, National Hospital Organization, 3Niigata Rheumatic Center, 4Department of Internal Medicine and Rheumatology, Juntendo University, 5Yokohama Minami Kyosai Hospital, 6Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, 7Department of Rheumatology and Infectious Diseases, Kitasato University, 8Tokyo Metropolitan Tama Medical Center, 9Himeji Medical Center, National Hospital Organization, 10Morioka Hospital, National Hospital Organization, 11Kyushu Medical Center, National Hospital Organization, 12Nagoya Medical Center, National Hospital Organization, 13Department of Medicine, Teikyo University, 14 Yokohama City University Medical Center, 15 Juntendo University School of Medicine

Background: TRIM21, also referred to as Ro52 or SS-A1, belongs to the tripartite motif- containing (TRIM) family. TRIM21 is an autoantigen recognized by autoantibodies in sera of patients with systemic lupus erythematosus (SLE) and Sjögren’s syndrome (SS). TRIM21 is induced by type I interferon, ubiquitylates proteins of the interferon-regulatory factor family, and regulates type I interferon and proinfl ammatory cytokines. It is not clear how these different aspects of TRIM21 can be reasonably explained. Until now, several small scale studies suggested the association of SNPs in TRIM21 with susceptibility to SLE and SS. However, to our knowledge, systematic association study which covered all the tagSNPs has not been reported. In this study, we conducted a systematic association study between SLE and TRIM21 in a Japanese case-control set with more than 1,000 individuals. Methods: Nine tagSNPs in TRIM21 region were selected based on JPT HapMap data with the criteria of minor allele frequency > 0.05 and r2 threshold of 0.80. 530 Japanese SLE and 518 healthy Japanese controls were genotyped for the tagSNPs using TaqMan SNP genotyping assay, and case-control association study was performed. Results: Among the 9 tagSNPs, marginal association was detected in 3 SNPs. At rs7947461 in intron 1, the frequency of the T/T genotype (P=0.04, odds ratio [OR] 0.72, 95% confi dence interval [CI] 0.53-0.99) was decreased. At rs9261010 in exon 2 coding for a synonymous substitution, T allele frequency (P=0.04, OR 0.81, 95%CI 0.67-0.99) and T/T genotype frequency (P=0.05, OR 0.62, 95% CI 0.39-1.00) were marginally decreased. Furthermore, at rs4144331 in the 3’ untranslated region, decrease in T allele frequency (P=0.04, OR 0.76, 95%CI 0.58-0.98) and in T/T genotype frequency (P=0.04, OR 0.75, 95% CI 0.56-0.99) were observed. Conclusion: TRIM21 polymorphisms may be associated with susceptibility to SLE.

188 Poster Presentation

P-26

Temperature during pregnancy infl uences birth size

Miki Kagami1, Enbo Ma2, and Yukiko Wagatsuma2

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

Background: Birth weight and length are known to fl uctuate with season of birth. However, it is uncertain which meteorological element has an effect upon birth weight and length, and which timing of pregnancy would explain such effect. Objectives: The purpose of this study is to examine whether temperature during pregnancy and which timing effects on size at birth. Methods: A large, randomized, controlled trial of food and micronutrient supplementation for pregnant women was conducted in Matlab, Bangladesh (MINIMat Study). The fetal growth data which included the size at birth and information of their mothers were obtained (n=3267, respectively). Meteorological data such as temperature, precipitation and daily sunshine hours were observed at the nearest observatory site of Bangladesh Meteorological Department. Re- sults: A seasonal pattern of birth weight and length was seen. Infants who were born in hot and dry season (March – May) tended to be heavier (not signifi cant). Infants born in winter (October – February) were shorter than those born in other seasons (Hot and dry season, P<0.01, Monsoon season; June – September, P<0.001). From the results of multivariate analy- ses, when the temperature at 8 weeks of gestation increased, birth length became shorter. On the other hand, temperature at the last month of pregnancy affected birth length in a reversed direction. For birth weight, as temperature increased at 17 and 19 weeks of gestation, birth weight was increased 4.2 to 4.7 mm, respectively. Conclusion: These fi ndings suggest that temperature affects both birth weight and length. More temperature increased at the last month of pregnancy, longer birth length became. For birth weight, the temperature at mid pregnancy affected positive way.

189 Poster Presentation

P-27

The intervention research on Domestic Violence prevention program for high school students

Tomoko Suga1,2 and Nobuaki Morita1

1Social Psychiatry and Mental Health, Human Care Science, University of Tsukuba 2Ibaraki National College of Technology

This study examined the effects of the Domestic Violence prevention program that we had made as an original program for high school students in Japan. We named the program “Educational program to respect each other to have a good relationship. How do we prevent Domestic Violence?” The program contents are 1)meet people, 2)What is ‘respect’?, 3)story telling about DV, 4)relationship, 5)violence, 6)What is DV?, 7)make communication for respect. The intervention students were 78 persons, and control students 73 persons. The intervention group answered the questionnaire through an experimental repeated design, before program, after program and 1 month later. The control group was measured the scores of questionnaire ‘recognition of controlled relationship’ and ‘coercive action’. The effect of ‘recognition of controlled relationship’ and ‘coercive action’ were kept after the program, but decreased 1 month later almost to the same values seen before program. However, when the students were asked about the program, both boy’s students and the girl’s students found it useful even after one month has passed. It was suggested that high school students will assimilate the knowledge, but fi nd it hard to change their way of thinking toward violence.

190 NOTE

191 NOTE

192 Risk, Agent x, Science & Technology

Cultural Anthropology, Doctoral Program in History and Anthropology, University of Tsukuba

193 Sep 29 (Mon) Meeting Room 5

Risk, Agent x, Science & Technology

Chair Yasushi Uchiyamada University of Tsukuba

9:00-9:10 Yasushi Uchiyamada University of Tsukuba Introduction

Session 1

9:10-9:40 Paul Hansen University of Tsukuba Indexing Risk: Hearing More-than-human Publics in Japan

9:40-10:10 Robin O'Day University of Tsukuba Anti-Nuclear Activism and the Rise of Japan’s “Invisible” Civil Society

10:10-10:25 Daniel White University of Hosei Discussant

10:25-10:40 Akironi Kubo Hitotsubashi University Discussant

10:40-10:55 Discussion

11:00-12:00 Poster Session: Risk, Technology and Anthropology (Multimedia Room) 12:30-13:30 Lunch Session 2

13:30-14:00 Hiroki Fukagawa Kyoto University Curse of Uncertainty: Healing Ritual and Multiple Causes of Misfortune

14:00-14:30 Sophie Chave-Dartoen Unversity of Bordeaux Uncertainty, Risks, Catastrophes and Agency

14:30-14:45 Keiji Maegawa University of Tsukuba Discussant

14:45-15:00 Toru Yamada University of Tsukuba Discussant

15:00-15:15 Discussion

15:15-15:30 Coffee Break Session 3

Star Wars, International comparisons of public policies as tools of 15:30-16:00 Sébastien Guigner Sciences Po Bordeaux power: the case of health policies

16:00-16:30 Shuhei Kimura University of Tsukuba Technologies to make future

Agent x in the perceived world: a case of invisible uncanny in 16:30-17:00 Yasushi Uchiyamada University of Tsukuba Fukushima

National Institute for Agro- 17:00-17:20 David Sprague Discussant Environmental Sciences

17:20-17:40 Junko Teruyama University of Tsukuba Discussant

17:40-18:00 Discussion

194

10 / 26 ページ Sep 29 (Mon) Meeting Room 5

Risk, Agent x, Science & Technology

Chair Yasushi Uchiyamada University of Tsukuba

9:00-9:10 Yasushi Uchiyamada University of Tsukuba Introduction

Session 1

9:10-9:40 Paul Hansen University of Tsukuba Indexing Risk: Hearing More-than-human Publics in Japan

9:40-10:10 Robin O'Day University of Tsukuba Anti-Nuclear Activism and the Rise of Japan’s “Invisible” Civil Society

10:10-10:25 Daniel White University of Hosei Discussant

10:25-10:40 Akironi Kubo Hitotsubashi University Discussant

10:40-10:55 Discussion

11:00-12:00 Poster Session: Risk, Technology and Anthropology (Multimedia Room) 12:30-13:30 Lunch Session 2

13:30-14:00 Hiroki Fukagawa Kyoto University Curse of Uncertainty: Healing Ritual and Multiple Causes of Misfortune

14:00-14:30 Sophie Chave-Dartoen Unversity of Bordeaux Uncertainty, Risks, Catastrophes and Agency

14:30-14:45 Keiji Maegawa University of Tsukuba Discussant

14:45-15:00 Toru Yamada University of Tsukuba Discussant

15:00-15:15 Discussion

15:15-15:30 Coffee Break Session 3

Star Wars, International comparisons of public policies as tools of 15:30-16:00 Sébastien Guigner Sciences Po Bordeaux power: the case of health policies

16:00-16:30 Shuhei Kimura University of Tsukuba Technologies to make future

Agent x in the perceived world: a case of invisible uncanny in 16:30-17:00 Yasushi Uchiyamada University of Tsukuba Fukushima

National Institute for Agro- 17:00-17:20 David Sprague Discussant Environmental Sciences

17:20-17:40 Junko Teruyama University of Tsukuba Discussant

17:40-18:00 Discussion

195

10 / 26 ページ Indexing Risk: Hearing More-than-human Publics in Japan

Paul Hansen

University of Tsukuba

In 2003 companion animals began to outnumber children under the age of sixteen in Japan and this divide has increased yearly. Noting the ever-expanding range of goods and services geared towards particular and significant furry others (cf. Haraway 2008, Derrida 2008), it is clear that domesticated dogs and cats play an ever-expanding role in urban Japan’s social and cultural milieu. Post-2011, popular depictions of rural suffering did not feature human inhab- itants alone; domestic animals captured much media attention. Distraught livestock farmers brought to the fore a sense that these non-humans represented more to them than a means to an end – their value was expressed as more than ‘livestock’ or a living commodity. This paper questions if these more-than-human conditions can be read as an index of growing precarity in Japan; perhaps even an indication of the precariousness of being Japanese. Utilizing the con- cept of “flexible personhood” (Shir-Vertesh 2012) alongside ideas drawn from cosmopolitan studies and posthuman theory this paper suggests that risks and precarity in Japan can be read in registers that move beyond the human.

196 Anti-Nuclear Activism and the Rise of Japan’s “Invisible” Civil Society

Robin O’Day

University of Tsukuba

In the weeks and months after the Tohoku disaster on March 11, 2011, tens of thousands of people took to the streets in Japan to protest and voice their concerns about the government’s role in exacerbating the crisis. Of particular focus within these protests were the perceived mishandling of the Fukushima Daiichi nuclear accident, and the broader dangers associated with relying on nuclear energy. These protests were significant since they were some of the largest street protest to occur in Japan since the 1960s and 1970s when hundreds of thousands took to the streets of Tokyo to oppose the revisions of the US-Japan Security Treaty (AMPO). How should scholars, therefore, interpret and explain the recent anti-nuclear street protests within a broader perspective on popular forms of political dissent in Japan? What do these protests suggest about the Japanese public’s willingness to accept the risks associated with nuclear energy? Furthermore, what can these protests tell us about civil society’s ability to challenge, oppose, and re-frame the official narratives of safety and risk promoted by state, corporate, and scientific experts? In an effort to help answer these questions, this paper approaches these questions ethnographically from the perspectives of different social movements that were organizing public protests around precarious employment and growing economic inequalities before the disaster. What role did these groups play in the post-3.11 protests? How did they shape the street politics of the 3.11 crisis? Conversely, how did the crisis shape their politics?

197 Curse of Uncertainty: Healing Ritual and Multiple Causes of Misfortune

Hiroki Fukagawa

Kyoto University

In this presentation, I consider how people deal with the cause of illness and misfortune, in terms of technology and risk management, taking the case of healing rituals in the New Guinea Highlands. In Enga Province, when a person is angry with others by the conflicts, the feeling itself becomes a curse. It is assumed that the cursed person is injured in a sickness and an unexpected accident, and dies. Moreover, angry person also becomes sick and dies. Therefore social discord appears as bodily disorder. The method to remove a curse is to restore a disturbed social relation. It takes the form of the healing ritual. However, the curse is not the only cause of illness and misfortune. There are multiple causes. Therefore they perform the healing ritual in order to solve the problem of unknown causes (agent x). Technology is used to solve the problem. In this presentation, I analyze the case that healing rituals fails and examine technology to treat the uncertainties of life such as illness and misfortune.

198 Uncertainty, Risks, Catastrophes and Agency

Sophie Chave-Dartoen

Université de Bordeaux

In the western/modern societies, to raise the question of uncertainty in terms of risks implies a focus on the choices (technical, commercial, political…) that individual or collective social agents operate. To raise this question in terms of disaster reaches another issue: it emphasizes disorders within the distinct domains that nature and culture constitute. This communication tries to keep at distance this double dichotomy to analyse it, considering the presuppositions on which it is based. The cultural construction associated with the concept of risks will be presented via a fast review of its debt to the first Anglo-Saxon economic liberalism and to the French Lumières. It will then be pointed out through the contrast offered by the study of a totally different case. The way relationships to the world and human agency are conceived in a Polynesian society will be used for comparison. I will then examine how the question of catastrophes is handled, risks are perceived and experienced, in the contemporary Wallisian society which is open to the rest of the world and connected to globalized networks and flows. These developments will open a reflection on the translatability of the concept of risk and on its operational character, in particular in the context of national and international management of risks and of the flows it can suppose.

199 Stat wars International comparisons of public policies as tools of power: the case of health policies

Sébastien Guigner

Associate professor, Institute of Political Studies, University of Bordeaux

International comparisons have become unavoidable for anyone who wants to govern modern democracies. The belief in the virtue of international comparisons is part of a wider dynamic where public policy and governance are more and more expected to be rationally conducted to face society challenges. Since it is believed that comparing is the better way to produce “evidence-based social science”, comparing internationally would be the better way to produce “evidence-based policies”. But the many and recurrent flaws of these comparisons cast doubt on their actual role and effects. Among the most common deficiencies are the comparability of data, the lack of clear definitions of terms and the state-centrism of comparisons. Why thus such a success of international comparisons among policy-makers? The study of the health field shows that under the guise of rationalizing and depoliticizing decisions, international comparisons are less a tool of learning than a tool of power. Actually, behind their technical substrate and their apparent neutrality, international comparisons carry values, interests and power relations. Basically, international comparisons can be associated with social statistics, which can “have two purposes, one public, the other often hidden. Their public purpose is to give an accurate, true description of society. But people also use statistics to support particular views about social problems. Numbers are created and repeated because they supply ammunition for political struggles, and this purpose is often hidden behind assertions that numbers, simply because they are numbers, must be correct” (Best, 2012: 13). That is probably the fundamental reason for success, rather than fostering learning. First, comparisons hide that policies are always value-laden; they deliver “the truth”. Comparisons seems to be in themselves “scientific” and thus “true”. Moreover, the language through which comparisons are presented create effects of truth which rule out any debate. Second, international comparisons create political pressure, notably because this language is easily understandable and particularly well-suited for the mass media.

200 Technologies to make future

Shuhei Kimura

University of Tsukuba

This paper examines so-called “reconstruction” of a coastal village in Iwate Prefecture, Japan. The consequences of the East Japan Great Earthquake still poses a challenge to both society and anthropology, especially in Japan. By providing ethnographic sketches of the ways the affected people and people coming there from outside embrace the future, this paper observes how the low and high technologies such as tsunami risk assessment, project proposals and reconstruction plan, and phatic labor (Elyachar 2010) frame the temporality of the village. The process of reconstruction is on the one hand iteration of past (and future) event, but simultaneously, on the other hand, it is an entanglement of infinite beginnings and ends, in which people struggle to reconcile their past and future in their own rhythm. Then this paper explores how future is being made in between linear and cyclic time.

201 Agent x in the perceived world: a case of invisible uncanny in Fukushima

Yasushi Uchiyamada

University of Tsukuba

In a ramen shop in Hisanohama, a small fishing port, which was seriously affected by the tsunami, the fire, and the Fukushima Daiichi nuclear disaster, two local women and a munici- pal employee were talking right next to me. The tone was somewhat intent. “I wonder if the municipality does the radiological test of well water,” says the first woman. “Is there a counter in the City Hall where I could ask for a water analysis? You know, our granny [her mother] has been using the well water for every thing for the past three years… and she says “I am still alive so I think I am alright”… but it’s worrying.” “That’s not our responsibility,” says the municipal employee, “that’s the jurisdiction of the public health center.” “Do they check radioactive materials?” “Well… that’s… unlikely.” The woman goes silent. “The more fre- quently you use well water,” the second woman intervenes, “the cleaner it becomes, isn’t it?” The first woman and the municipal employee do not respond to her assurance. She then casts a glace at me. I nod vaguely. The sense experience of the lived body in the world seemed to have become a misplaced phenomenology in this particular instance. There are imperceptible agents at work in the environment. We are anxious about their efficacies. In this paper I shall describe the awkward milieus of living things in the post-3/11 Fukushama, and then I shall revisit the life-world of Husserl and Merleau-Ponty to discuss the problematic notion of given- ness of the lifte-world from the interactionist perspective. In what ways is the surrounding world given?

202 NOTE

203 NOTE

204 Life and Medical Sciences in South East Asia

Faculty of Medicine, University of Tsukuba

205 Sep 29 (Mon) Meeting Room 6

Life and Medical Sciences in South East Asia

Chair Koji Hisatake University of Tsukuba Institute of Tropical Biology, Viet Nam The genetic relationship of Vietnamese pigs in Central Highlands 13:30-13:55 Hoang Nghia Son Academy of Science and assessed by cytochrome b Technology

Biotechnology Center of Influence of Wzz gene on the pathogenicity of knock out gene 13:55-14:20 Binh Nguyen Quoc Ho Chi Minh City, Vietnam Edwardsiella ictaluri and Aeromonas hydrophila strains in catfish

Biomedical Sciences in Indonesia: A cutting-edge knowledge in the 14:20-14:45 Septelia Inawati Wanandi Universitas Indonesia era of globalization

14:45 -15:00 Tea Break Chair Hoang Nghia Son Institute of Tropical Biology Exploiting the microorganism diversity from Indonesia’s biosphere 15:00-15:25 Amarila Malik Universitas Indonesia for potential applications in health, pharmaceutical and nutrition: a mini review University of Science, Age-Accelerated Locomotion Deficit and Dopaminergic Neuron 15:25-15:50 Dang Thi Phuong Thao Vietnam National University Degeneration in Drosophila Ubiquitin Carboxyl-Terminal Hydrolase Ho Chi Minh City Knockdown Model

Manipulation of Klf4 expression generates partially reprogrammed 15:50-16:15 Koji Hisatake University of Tsukuba iPS cells paused at successive stages of reprogramming

16:15-16:30 Tea Break Chair Septelia Inawati Wanandi Universitas Indonesia Multidrug Resistance MDR1 Gene Polymorphism (C3435T) in Pediatric 16:30-16:50 Rina Mutiara Willy Universitas Indonesia Acute Lymphoblastic Leukemia patients in Indonesia National Referral Hospital,

The sensitivity of breast cancer stem cells to doxorubicin modulated 16:50-17:10 Resda Akhra Syahrani Universitas Indonesia by oxidative stress

University of Science, Establishment of herbal collection and Evaluation of herbal bioactivity 17:10-17:25 Nguyen Thi Thanh Nhan Vietnam National University in wound healing Ho Chi Minh City

Analysis of adipose tissue-derived mesenchymal stem cells from 17:25-17:40 Vuong Cat Khanh University of Tsukuba chronic kidney disease patients

17:40-17:55 Rudy University of Tsukuba Molecular Mechanism of Gpnmb-inducible Tumorigenesis

17:55 Koji Hisatake University of Tsukuba Closing statement

206

21 / 26 ページ Sep 29 (Mon) Meeting Room 6

Life and Medical Sciences in South East Asia

Chair Koji Hisatake University of Tsukuba Institute of Tropical Biology, Viet Nam The genetic relationship of Vietnamese pigs in Central Highlands 13:30-13:55 Hoang Nghia Son Academy of Science and assessed by cytochrome b Technology

Biotechnology Center of Influence of Wzz gene on the pathogenicity of knock out gene 13:55-14:20 Binh Nguyen Quoc Ho Chi Minh City, Vietnam Edwardsiella ictaluri and Aeromonas hydrophila strains in catfish

Biomedical Sciences in Indonesia: A cutting-edge knowledge in the 14:20-14:45 Septelia Inawati Wanandi Universitas Indonesia era of globalization

14:45 -15:00 Tea Break Chair Hoang Nghia Son Institute of Tropical Biology Exploiting the microorganism diversity from Indonesia’s biosphere 15:00-15:25 Amarila Malik Universitas Indonesia for potential applications in health, pharmaceutical and nutrition: a mini review University of Science, Age-Accelerated Locomotion Deficit and Dopaminergic Neuron 15:25-15:50 Dang Thi Phuong Thao Vietnam National University Degeneration in Drosophila Ubiquitin Carboxyl-Terminal Hydrolase Ho Chi Minh City Knockdown Model

Manipulation of Klf4 expression generates partially reprogrammed 15:50-16:15 Koji Hisatake University of Tsukuba iPS cells paused at successive stages of reprogramming

16:15-16:30 Tea Break Chair Septelia Inawati Wanandi Universitas Indonesia Multidrug Resistance MDR1 Gene Polymorphism (C3435T) in Pediatric 16:30-16:50 Rina Mutiara Willy Universitas Indonesia Acute Lymphoblastic Leukemia patients in Indonesia National Referral Hospital, Jakarta

The sensitivity of breast cancer stem cells to doxorubicin modulated 16:50-17:10 Resda Akhra Syahrani Universitas Indonesia by oxidative stress

University of Science, Establishment of herbal collection and Evaluation of herbal bioactivity 17:10-17:25 Nguyen Thi Thanh Nhan Vietnam National University in wound healing Ho Chi Minh City

Analysis of adipose tissue-derived mesenchymal stem cells from 17:25-17:40 Vuong Cat Khanh University of Tsukuba chronic kidney disease patients

17:40-17:55 Rudy University of Tsukuba Molecular Mechanism of Gpnmb-inducible Tumorigenesis

17:55 Koji Hisatake University of Tsukuba Closing statement

207

21 / 26 ページ The genetic relationship of Vietnamese pigs in Central Highlands assessed by cytochrome b

Hoang Nghia Son

Animal Biotechnology Department, Institute of Tropical Biology, Viet Nam Academy of Science and Technology

To estimate the genetic relationship of Vietnamese pigs in Central Highlands, we com- pared cytochrome b sequences of Vietnamese wild boars and Vietnamese domestic pigs with other Asian and European wild boars. The results showed that there were two wild boar popu- lations locating in Vietnam Central Highlands including wild boars of group I and wild boars of group II. The Vietnamese wild boars of group II and domestic pigs were genetically close to Asian A1 and Asian A2 wild boar groups, whereas the Vietnamese wild boars of group I were genetically distinct from Asian A1, Asian A2 wild boar groups. The phylogenetic tree demonstrated that the Vietnamese wild boars of group I were clustered in one clade which was distinct from Asian wild boars and Europe wild boars. In addition, the Vietnamese wild boars of group I were estimated to have diverged from European wild boars at 421500 YBP, indicat- ing that Vietnamese wild boar of group I could be isolated from other Asian wild boars. The single nucleotide polymorphism analysis showed that three Asian haplotypes were contributed in Vietnamese wild boars including A3 (TATG) haplotype in Vietnamese wild boar of group I and A1 (CATA) haplotype and A2 (CATG) haplotype in Vietnamese wild boars of group II. The A1 haplotype and A2 haplotype were also distributed in Vietnamese domestic pigs. Thus, there is a high possibility that Vietnam Central Highlands is a principal source for research on genetic diversity in Asian wild boar and domestic pig populations.

208 Influence of Wzz gene on the pathogenicity of knock out gene Edwardsiella ictaluri and Aeromonas hydrophila strains in catfish

Binh Nguyen Quoc

Biotechnology Center of Hochiminh City, Vietnam

Wzz gene is known as the regulator for the length of the O-antigen in the lypopolysacha- ride of bacterial cell wall. The length of the O-antigen chain can be determined the immunity respond of the host against pathogen bacteria. In the goad to create attenuated pathogen bacte- rial strains using as live vaccine for catfish, the Wzz gene of E. ictaluri and A. hydrophila was deleted in different length. All mutants knock-out Wzz gene of both E. Ictaluri and A. Hy- drophila shown a great lower pathogenicity than that of wild-type. Interestingly, the complete gene deletion of the Wzz gen in both cases showing a remarkably low pathogenicity compared to the partial deletion. The attenuated knock out gene Wzz gene of E. ictaluri can be use as a live attenuated vaccine for the catfish. Those results clearly show that the pathogenicity of E.ictaluri and A. hydrophila on the catfish determined by Wzz gene activity.

209 Biomedical Sciences in Indonesia: A cutting-edge knowledge in the era of globalization

Septelia Inawati Wanandi*

*Department of Biochemistry and Molecular Biology, Faculty of Medicine,Universitas Indonesia [email protected]

For many years, Indonesia - an archipelago country with unique diversity - has experienced the impact of globalization in almost every field of life aspects. The increasing globalization of health sector such as the mobilization of health professionals and the use of new technologies has encouraged the improvement of medical sciences. A significant rise of biomedical sciences as a cutting-edge knowledge of medical sciences has been observed during the last decade in Indonesia, which involved the advancement of technology based on applied theory and triggering the approach of translational medicine. The enhancement of the utilization of biomedical skills can be seen in numerous activities in medicine, such as the development of diagnostic tools, preventive and therapeutic agents, including targeted therapy, and therefore has led to an increased necessity of biomedical analysis in the clinical practice of physicians. An example of ‘Millennium Development Goals’ implementation in Indonesia influenced by the advancement of biomedical sciences is the development of vaccine originated from Indo- nesian virus strain in order to reduce child mortality. Globalization has also improved the standard qualification of biomedical education in Indonesia through international network- ing and collaboration. It should be realized, however, that these improvements could not be separated from the supports of Indonesian government and private companies through health policies and research funding. Nowadays, scientists all over the world believe that the future of biomedical sciences is promising due to its important role in the medical field. Biomedical sciences are not just basic theories, but would also play a major role in numerous health indus- tries in Indonesia in the era of globalization.

210 Exploiting the microorganism diversity from Indonesia’s biosphere for potential applications in health, pharmaceutical and nutrition: a mini review

Amarila Malik1, Shu Ishikawa2, Nick C. K. Heng3, Slavko Krlaj4, Iwao Ohtsu2, Naotake Ogasawara2, Hiroshi Takagi2, Lubbert Dijkhuizen4

1Division of Pharmaceutical Biotechnology, Faculty of Pharmacy, Universitas Indonesia, Indonesia 2Graduate School of Biological Sciences, Nara Institute of Science and Technology, Japan 3Sir John Walsh Research Institute, University of Otago, New Zealand 4Groningen Biomolecular and Biotechnology Institute, Rijksuniversiteit Groningen, The Netherlands E-mail:[email protected]

Indonesia is known for its mega-biodiversity. Bacteria that have shown an important economic value is lactic acid bacteria (LAB) due to their application in food, and have potential uses in health and pharmaceutical. Exopolysaccharide (EPS) produced by LAB has been widely used as prebiotic (e.g. GOS and FOS), and as protein/peptide stabilizer in formulation of biotech drugs (e.g. inulin). Enzyme involved in homo-EPS synthesis are the sucrases, i.e. glucansucrases (GTF, GS), and fructansucrases (FTF, FS). Our study aimed to exploit potential LAB strain obtained from various local sources which carries potential gene/genes to be developed for the production of useful substances to be applied in health, pharmaceutical, and nutrition. Strain Weissella confusa MBF8-2 showed single gtf and ftf, while W. confusa MBF8-1 carries two putative gtf genes; Weissella is a genus which has not been reported much for sucrase encoding gene. Strain W. confusa MBFCNC2-1 carries inulosucrase type of ftf gene but possessed a unique feature of fructansucrase gene sequence. A recombinant sucrosephosphorylase (SPase), an enzyme able to transfer glucosyl moiety to various sugars and sugar alcohols, and phenolic or alcoholic –OH groups of various substances, was successfully cloned and expressed in E. coli from Leu. mesenteroides MBFWRS-3(1) strain; it showed 98.40% activity as of the SPase reference protein. Some LAB also produce bacteriocins like inhibitory substance (BLIS). The resistance of microbe to the existing antibiotic is of highly concern; therefore developing an antibiotic complement for bacterial chemotherapy strategy has been the center of attention. In an attempt to obtain recombinant antimicrobial peptide, sequencing of whole genome sequence of strain MBF8-1 has been carried-out, while of the strongest BLIS producer strain, Streptococcus macedonicus MBF10-2, will be next. Bacteria evolved defense mechanisms against stress that allow them to withstand harsh conditions and sudden environmental changes. We studied how LAB response to growth condition by using advances genomic technique RNA-seq.

Keywords: sucrase, sucrosephosphorylase, bacteriocin, Weissella, Streptococcus macedonicus

211 Multidrug Resistance MDR1 Gene Polymorphism (C3435T) in Pediatric Acute Lymphoblastic Leukemia patients in Indonesia National Referral Hospital, Jakarta

Rina Mutiaraˡ, Bernadius Agustinus², Christian Badia Sitompul², Djajadiman Gatot³, Amarila Malik²

1Graduate School of Biomedicine, Faculty of Medicine, Universitas Indonesia, UI Campus Salemba, Jalan Salemba Raya no. 4, Jakarta 10430, Indonesia 2Pharmaceutical Biotechnology Division, Faculty of Pharmacy, Universitas Indonesia, UI Campus Depok, Depok 16424, Indonesia 3Cipto Mangunkusumo Hospital, Jalan Diponegoro no. 71, Jakarta 10320, Indonesia

Acute lymphoblastic leukemia (ALL) is the most frequently occurring cancer in children. The main problem is 25–30% of the patients will experience a relapsing that leads to die of teenagers. There were estimated 4100 new cases pediatric ALL every year in Indonesia. Based on data in pediatric oncology Child Health Department Cipto Mangunkusumo Hospital period 2005-2011 was found 40% patients relapse of 126 pediatric ALL. The Multi Drug Resistance 1 (MDR1) gene codes for P-glycoprotein (P-gp) is an ATP-dependent efflux pump which has great importance in elimination of several important drugs and xenobiotic. It has been shown to be polymorphic. One of the multiple variants of the MDR1 gene is namely C3435T. It has been shown to modulate the metabolism and thus the response to the drug or xenobiotic substrates for P-gp such as steroid, anthracycline and Vinca alkaloid which associated with drug resistance mechanism. In many studies this polymorphism also can be used to evaluate the contribution of candidate gene to the understanding genetic susceptibility to pediatric acute lymphoblastic leukemia (ALL). Our study was first, to analyze the MDR1 gene polymorphism profile. We screened for the C3435T polymorphism 44 children with ALL, using PCR-RFLP assay with MboI as the restriction enzyme. We found 6 (13,6%) ALL samples were digestible (C allele) and 38 (86,4%) were indigestible. C allele indicates high expression of p-gp which eliminates ant leukemic drug, resulting in high risk diagnosis. On the other hand, the T allele which was found abundant in our patients might be associated with the incidence of ALL. Further studies on SNP are in progress to confirm these results, as well as expression of multidrug resistance related protein (MRP) gene.

Key words: Acute lymphoblastic leukemia, relapse, MDR1, P-glycoprotein, polymorphism, PCR- RFLP

212 The sensitivity of breast cancer stem cells to doxorubicin modulated by oxidative stress

Resda Akhra Syahrani1, Melva Louisa2 and Septelia Inawati Wanandi3

1Master Programme in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia 2Departement of Pharmacology, Faculty of Medicine, Universitas Indonesia 3Departement of Biochemistry and Molecular Biology, Faculty of Medicine, Universitas Indonesia

Breast cancer is serious global health problem being the second most common of all cancers and by far has been the highest incidence among other cancers in Indonesian women. Doxorubicin is an anthracycline antibiotic which induces cancer cell death by many mechanism, most importantly by generation of radical oxygen species (ROS). Although breast cancer is considered one of the most chemosensitive solid tumors, most initially tumors relapse and develop resistance to drugs, even to doxorubicin which is considered as the most active drug available for the treatments of breast cancer. It has been found that solid tumors contain a small number of population that are highly resistant to drug treatment, known as cancer stem cells (CSCs). The aim of this study is to analyze the sensitivity of breast cancer stem cells to doxorubicin. In our previous study, human breast CSCs (CD24-/CD44+) were sorted from breast cancer tissue of patient. Breast CSCs were treated with doxorubicin for 14 days. The effect of doxorubicin was examined by analyzing intracellular ROS level using superoxide probe dihydro-ethidium (DHE) and hydrogen peroxide probe 2’-7’-Dichlorodihydrofluorescein diacetate (DCFH-DA). The antioxidant defense system was analyzed using Real Time RT- PCR to determine the level of MnSOD mRNA expression. The result showed that the viability of breast CSCs treated with doxorubicin was first decreased on the second day and started to increase on the eight day of treatment, indicating reduced sensitivity of breast CSCs to doxorubicin after eight days of treatment. Interestingly, the level of ROS, both superoxides and hydrogen peroxides, as well as the level of MnSOD mRNA expression were increased on the second day and decreased on the eight day, revealing that the viability of breast CSCs was associated with their redox status. In conclusion, this study could suggest that the sensitivity of breast CSCs to doxorubicin was modulated by oxidative stress.

213 NOTE

214 Global Aging: Emerging Challenges and Opportunities

Division of Health Innovation and Nursing, Faculty of Medicine, University of Tsukuba

Center for Global Aging Tsukuba (CGAT), University of Tsukuba

215 Sep 29 (Mon) Special Conference Room

Global Aging: Emerging Challenges and Opportunities -CGAT Oral Session-

Chair Nanako Tamiya University of Tsukuba

9:00-12:30 Peter Lloyd-Sherlock University of East Anglia Long term care for older people in Latin America: a growing challenge

Gerhard Igl University of Kiel

Public Oral Presentation

Sep 30 (Tue) Special Conference Room

Global Aging: Emerging Challenges and Opportunities

Chair Masao Ichikawa University of Tsukuba

Political and social determinants of life expectancy in less developed 9:10-9:30 Chang-Chuan Chan National Taiwan University countries: a longitudinal study

Continuous quality improvement of primary care in an aging world: the 9:30-9:50 Marlene J. Egger University of Utah University of Utah Family Medicine Resident CQI Program

Effects of climate and air pollutants on human health: Multinational 9:50-10:10 Yue Leon Guo National Taiwan University studies

10:10-10:30 Yasushi Honda University of Tsukuba Population aging and climate change impact on heat-related mortality

10:30-11:00 Coffee Break

11:00-11:20 Holli A. DeVon University of Illinois at Chicago Effects of Aging on Coronary Heart Disease in the United States

Characteristics of Circulatory Diseases in Japan: Based on the 11:20-11:40 Tomoko Sankai University of Tsukuba Circulatory Risk in Communitiesy Study (CIRCS)

The Nurse Occupational Stressor Scale (NOSS) Development and 11:40-12:00 Judith SC Shiao National Taiwan University Mental Health Investigation

Development and dissemination of End-of-Life Care Nursing Education 12:00-12:20 Tomoyo Sasahara University of Tsukuba Consortium-Japan (ELNEC-J)

216

11 / 26 ページ Sep 29 (Mon) Special Conference Room

Global Aging: Emerging Challenges and Opportunities -CGAT Oral Session-

Chair Nanako Tamiya University of Tsukuba

9:00-12:30 Peter Lloyd-Sherlock University of East Anglia Long term care for older people in Latin America: a growing challenge

Gerhard Igl University of Kiel

Public Oral Presentation

Sep 30 (Tue) Special Conference Room

Global Aging: Emerging Challenges and Opportunities

Chair Masao Ichikawa University of Tsukuba

Political and social determinants of life expectancy in less developed 9:10-9:30 Chang-Chuan Chan National Taiwan University countries: a longitudinal study

Continuous quality improvement of primary care in an aging world: the 9:30-9:50 Marlene J. Egger University of Utah University of Utah Family Medicine Resident CQI Program

Effects of climate and air pollutants on human health: Multinational 9:50-10:10 Yue Leon Guo National Taiwan University studies

10:10-10:30 Yasushi Honda University of Tsukuba Population aging and climate change impact on heat-related mortality

10:30-11:00 Coffee Break

11:00-11:20 Holli A. DeVon University of Illinois at Chicago Effects of Aging on Coronary Heart Disease in the United States

Characteristics of Circulatory Diseases in Japan: Based on the 11:20-11:40 Tomoko Sankai University of Tsukuba Circulatory Risk in Communitiesy Study (CIRCS)

The Nurse Occupational Stressor Scale (NOSS) Development and 11:40-12:00 Judith SC Shiao National Taiwan University Mental Health Investigation

Development and dissemination of End-of-Life Care Nursing Education 12:00-12:20 Tomoyo Sasahara University of Tsukuba Consortium-Japan (ELNEC-J)

217

11 / 26 ページ Long term care for older people in Latin America: a growing challenge

Peter Lloyd-Sherlock

University of East Anglia

This paper will demonstrate the growing demand for long term care services in Latin America and the increasing pressures on the supply of informal care in the region. It will discuss current patterns of provision in the region, including state services, private sector pro- vision and family arrangements. It will identify a number of related policy challenges and discuss the scope for more comprehensive and coherent policies. Drawing on results of studies in Argentina, Mexico and Peru, particular attention is paid to the rapid growth in unregulated, semi-legal care homes and the use of paid domestic workers and young children as informal carers.

218 Political and social determinants of life expectancy in less developed countries: a longitudinal study

Ro-Ting Lin1, Ya-Mei Chen1, Lung-Chang Chien2 and Chang-Chuan Chan1,3

1Institute of Occupational Medicine and Industrial Hygiene, college of Public Health, National Taiwan University 2Department of Internal Medicine, Division of Health Behavior Research, School of Medicine, Washington University 3Global Health Center, College of Public Health, National Taiwan University

This study aimed to examine the longitudinal contributions of four political and socioeconomic factors to the increase in life expectancy in less developed countries (LDCs) between 1970 and 2004. We collected 35 years of annual data for 119 LDCs on life expectancy at birth and on four key socioeconomic indicators: economy, measured by log10 gross domestic product per capita at purchasing power parity; educational environment, measured by the literacy rate of the adult population aged 15 years and over; nutritional status, measured by the proportion of undernourished people in the population; and political regime, measured by the regime score from the Polity IV database. Using linear mixed models, we analyzed the longitudinal effects of these multiple factors on life expectancy at birth with a lag of 0-10 years, adjusting for both time and regional correlations. The LDCs’ increases in life expectancy over time were associated with all four factors. Political regime had the least influence on increased life expectancy to begin with, but became significant starting in the 3rd year and continued to increase, while the impact of the other socioeconomic factors began strong but continually decreased over time. The combined effects of these four socioeconomic and political determinants contributed 54.74% - 98.16% of the life expectancy gains throughout the lag periods of 0-10 years. Though the effect of democratic politics on increasing life expectancy was relatively small in the short term when compared to the effects of the other socioeconomic factors, the long-term impact of democracy should not be underestimated.

219 Continuous quality improvement of primary care in an aging world: the University of Utah Family Medicine Resident CQI Program

Marlene J1. Egger, Susan Pohl2

1Division of Public Health, Department of Family and Preventive Medicine, University of Utah 2Division of Family Medicine, Department of Family and Preventive Medicine, University of Utah

Continuous quality improvement (QI) has been adopted extensively by industry to keep pace with a quickly-changing world. Its uptake is increasing in clinical care and public health. In the face of resource pressures driven by global aging, QI provides rapid-cycle tools to analyze and improve health care processes. American medical schools now build training in clinical quality improvement (CQI) into medical undergraduate and residency curricula. Family medicine board certification now requires CQI activities in one’s own practice. Elements of a successful CQI training program include policy mandates; a physician-led program with a limited, focused curriculum; hands-on experience with a project important to the clinic; designated time and resources to work on it; being held accountable by the clinic; population- based thinking; interprofessional respect; and teamwork skills. This case study shows how the University of Utah Family Medicine Resident CQI Program uses the Batalden FOCUS- PDSA paradigm for rapid-cycle CQI, together with a limited toolset of resources available at the Institute for Healthcare Improvement, to equip family medicine physicians with skills they will use to improve care of an increasingly aging society.

220 Effects of climate and air pollutants on human health: Multinational studies

Yue Leon Guo1,2, Yasushi Honda3, Ho Kim4

1Environmental and Occupational Medicine, National Taiwan University (NTU) College of Medicine and NTU Hospital, Taipei, TAIWAN 2Institute of Occupational Medicine and Industrial Hygiene, NTU College of Public Health, Taipei, TAIWAN 3Faculty of Health and Sport Sciences, University of Tsukuba, Tsukuba, Japan 4Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea

Climate change and air pollution have been important health issues in many countries. International collaborations provide opportunities for examining in depth hypotheses and phenomena that have never been possible in the past. Pooled environmental data like climate factors and air pollutants can be combined with outcome data like mortality and morbidity. Comparisons of climate effects on mortality have been made to reveal consistent findings that cold and warm temperature are associated with increased deaths, especially due to cardiovascular and respiratory diseases. On the other hand, optimal temperature in regard to mortality varies among different countries. Health effects have been related to air pollutants, such as carbon monoxide, nitrogen oxides, ozone, particulates, and sulfur dioxide, among collaborative countries. Mortality and emergency room visits due to cardiovascular and respiratory diseases appear to be sensitive outcomes caused by air pollutants. Susceptible sub-populations can be identified by meta-analyses. For example, adverse birth outcomes have been related to air pollutants. Elderly people are especially vulnerable to temperature extremes and air pollutants. In conclusion, international collaborations with pooled environmental data and population outcome data result in large numbers of subjects and allow for cross-ethnical comparisons, as well as higher statistical power to examine hypotheses related to human health effects.

221 Population aging and climate change impact on heat-related mortality

Yasushi Honda

Faculty of Health and Sport Sciences

Heat-related mortality is statistically defined as follows: At a certain temperature, a mortality level of a population becomes lowest. This temperature is called “optimum temperature” (= OT). When the temperature is higher than the OT, the mortality level would be higher than that at the OT. The difference between these mortality levels is considered to be excess mortality due to heat, and thus defined as heat-related mortality. This heat-related mortality is one of the biggest mortality effect of the climate change in developed countries, and this impact has been included in the Climate Change Risk Assessment conducted by World Health Organization (the report of which will be published soon). This heat-related mortality, along with other general mortality, is higher for older people. In addition, for prevention of heat- related deaths, although frequent water supply and adequate use of air-conditioner are very important, elderly people’s sensitivity to heat is lower than younger people. This lack of sensitivity and mental deterioration of elderly people makes the prevention difficult. For these reasons, in developed countries including Japan, climate change impact on the heat-related mortality will be more serious because of the population aging. In the presentation, I will first demonstrate the heat-mortality relation in various countries and our finding that can be used for future projection of climate change impact on heat-related mortality. Then, showing the age-group specific heat-mortality relations, I will discuss about the impact of population aging on heat-related mortality.

222 Effects of Aging on Coronary Heart Disease in the United States

Holli A. DeVon

University of Illinois at Chicago; College of Nursing, Department of Biobehavioral Health Science

Background/Significance: Cardiovascular disease (CVD) is the leading cause of death and disability worldwide and older adults carry a higher burden of CVD. The purpose of this study was to determine if there were differences in clinical presentation, comorbidities, and healthcare utilization in Medicare eligible (≥65 years) and non-Medicare eligible (<65 years) adults with acute coronary syndrome (ACS). Methods: Patients admitted to five high volume emergency departments (ED) were enrolled. The 13-item validated ACS Symptom Checklist was used to measure symptoms on presentation to the ED. The Charlson Comorbidity Index (CCI) was used to assess comorbid conditions. Analysis of variance or Chi-square tests were used to evaluate group differences across age in clinical presentation, comorbidities, and healthcare utilization. Results: The convenience sample of 421 patients were predominantly male (73.4%), Caucasian (70.1%), and with a mean age of 61.7 years. There were more women (p=.032) and Caucasians (.003) in the older group. Older patients were more likely to be diagnosed with non-ST elevation myocardial infarction (p=.003); arrive to the ED by ambulance (p=.016), and be overweight (p<.0001) and were less likely to be a current smoker (p<.0001). As expected, older patients had a higher CCI mean score (p=.019) with a significantly higher incidence of cancer (p<.0001). Older patients were less likely to report chest pressure (p<.0001), chest discomfort (p=.010), and shortness of breath (p=.022), and experienced fewer symptoms (p=.038). Following discharge, younger patients made more calls to clinicians and had more clinic visits. Conclusions: There were more similarities than differences between older and younger groups in clinical presentation and health utilization in the six months following discharge. However, lack of chest pressure, chest discomfort, and shortness of breath, key symptoms triggering a decision to seek emergent care, may put elders at risk for delayed treatment.

223 Characteristics of Circulatory Diseases in Japan: Based on the Circulatory Risk in Communities Study (CIRCS)

Tomoko Sankai1,2, Kazumasa Yamagishi1,2, for the CIRCS Investigators

1Department of Public Health Medicine, Faculty of Medicine, University of Tsukuba 2Osaka Center for Cancer and Cardiovascular Diseases Prevention

The Circulatory Risk in Communities Study (CIRCS), which is a community-based dynamic prospective study on circulatory diseases, i.e. stroke and Coronary Heart Disease (CHD), has consisted of the four rural and one suburban communities in Akita and started from 1963, in Kochi started from 1969, and in Ibaraki prefectures started from 1981. The long-term follow-up investigations of the CIRCS have shown many characteristics on stroke and CHD among Japanese. The mortality and incidence rates of CHD in Japan have been observed to be lower than that in Western countries, and those of stroke in Japan have been observed higher. Further in stroke, the proportion of cerebral hemorrhage and lacunar infarction caused by arteriolosclerotic change in small penetrating arteries is higher and that of cortical artery infarction caused by atherosclerotic change is lower in Japan than in Western countries. Hypertension and its complications were the most significant risk factors of stroke and CHD. On the other hand, serum total cholesterol is inversely associated with cerebral hemorrhage among Japanese. The recent studies shows that the dietary changes, such as lowered sodium intake and increased animal food intake, which may lead to decrease stroke incidence through declining blood pressure level. However, not yet to increase CHD incidence through rising serum total cholesterol level except male residents in urban area. In order to achieve the aim of a reduction by half of the incidence of stroke in Kyowa town in Ibaraki, a community-based population approach to prevent hypertension, nutritional education campaigns to reduce salt intake has been conducted since 1981. After that, the systolic and diastolic blood pressure level in the participants of annual medical examinations in Kyowa town had begun to decline. In thirty years follow-up, elderly people’s stroke incidence rate was reduced almost by half, and also they have led to control of national insurance medical expenses and a premium for care insurance compared with neighbor communities.

224 The Nurse Occupational Stressor Scale (NOSS) Development and Mental Health Investigation

Dr. Judith SC Shiao

Associate Professor, Department of Nursing College of Medicine, National Taiwan University

Nurses are the frontline providers of healthcare and are exposed to stressful work environment, and their job characteristics are important predictors of occupational stress- health outcome. The adverse outcomes of occupational stress on nurse’s physical health and emotional well-being have been well documented. In the last few years, there have been increasing concerns over the adverse health impacts of job stress and building positive health practice environment, to promote nurses’ retention rate. The Occupational Safety and Health Act were passed in Taiwan in 2013, aimed to reduce occupational chemicals, physical and biological hazards for all workers. Under this new act, the employers are also responsible to provide a friendly work environment in terms of mentor health. Most of nurse work stress studies are reporting self-perceived health status of nurses using developed measurement tools. However, the magnitude of the adverse effects on nurses’ general health, i.e. prevalence and types of health outcomes of occupational stress in nurses, commonly seen nurses’ job stressors, should be identified. In 2013, the Institute of Occupational Safety and Health and National Taiwan University Nursing Department had conducted a join study entitled: “Risk assessment and factor analysis for occupational stress in nurses”, and developed a draft “The Nursing Characteristics related Job Stress Scale”. In 2014, the scale will be amended, tested and finalized as: {The Nurse Occupational Stressor Scale (NOSS) Development and Mental Health Investigation}. A nationwide survey is intended using the new scale, to early detect nurses with high score of occupational stress. A psychiatric physician will be consulted for those cases with significant high scores, and to confirm the diagnosis if there are psychiatric conditions detected by the NOSS. A user guide for the NOSS will also be prepared. Recommendations related to reduce/avoid nurses’ occupational stressors are to be discussed and formulated.

225 Development and dissemination of End-of-Life Care Nursing Education Consortium-Japan (ELNEC-J)

Tomoyo Sasahara1 and Tomoko Arahata2

1Health Innovation and Nursing, Faculty of Medicine, University of Tsukuba 2Nursing Sciences, Comprehensive Human Sciences, University of Tsukuba

The rapidly increasing percentage of elderly people is a growing issue in Japan. In fact, people aged 65 or older will account for about 40 percent of the total population by 2060. This means that our society will face unprecedented demand for the provision of end-of-life care. The End-of-Life Care Nursing Education Consortium (ELNEC) project is a national education initiative that began in 2000 in the United States to improve end-of-life care. The project provides nurses with a higher level of training in end-of-life care so they can pass on these essential skills to staff nurses. ELNEC has 7 curricula including in ELNEC-Core. They are systematic and comprehensive programs and expanding internationally. From 2007, our research group began to develop the Japanese version of ELNEC-Core. After translating the original guide into Japanese, we modified it to apply to Japanese culture and health care system. The Japanese version called “ELNEC-J core curriculum trainer’s guide” was prepared by adding a module named “End-of-Life Care for Geriatric” to original 9 modules: “Palliative Nursing Care,” “Pain Management,” “Symptom Management,” “Ethical Issues in Palliative Care Nursing,” “Cultural and Spiritual Considerations in End-of-Life Care,” “Communication,” “Loss, Grief & Bereavement,” “Preparation for and Care at the Time of Death,” and “Achieving Quality Palliative Care.” In 2009 the ELNEC-J “Train the Trainer” program was first conducted by the Japanese Society for Palliative Medicine and now there are 997 ELNEC-J trainers. ELNEC-J trainers have conducted an end-user program in their institution or region using the ELNEC-J core curriculum trainer’s guide and the number of end-user programs held has reached 221, providing education to 6,787 staff nurses. The ELNEC-J project has been successful and more staff nurses are expected to participate in the end-user program to provide more quality end-of-life care for elderly people.

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227 NOTE

228 Broadening your horizons international collaboration in the life sciences

Human Frontier Science Program

229 Sep 29 (Mon) International Conference Room

Broadening your horizons international collaboration in the life sciences

Human Frontier Science 12:30-12:40 Hideki Mizuma Program Broadening your horizons – international collaboration in the life sciences Human Frontier Science 12:40-13:30 Goeff Richards Program

230

15 / 26 ページ Sep 29 (Mon) International Conference Room

Broadening your horizons international collaboration in the life sciences

Human Frontier Science 12:30-12:40 Hideki Mizuma Program Broadening your horizons – international collaboration in the life sciences Human Frontier Science 12:40-13:30 Goeff Richards Program

231

15 / 26 ページ Broadening your horizons – international collaboration in the life sciences

Goeff Richards and Hideki Mizuma

Human Frontier Science Program

HFSP (the Human Science Frontier Program) was established to encourage innovative international collaboration in the life sciences. Working abroad for postdoctoral studies enables young scientists to obtain a wider understanding on the way science is conducted outside of their home institute. It is challenging but will lay the basis of a modern international scientific career. Similarly young scientists setting up their own laboratories should be aware of the possibilities of collaborative research to bring new approaches into their field. In this talk we will discuss the HFSP programs (fellowships and grants) that can help in making these important career steps. http://www.hfsp.org http://jhfsp.jsf.or.jp (Japanese sister site)

Geoff Richards’ scientific career started with an entrance scholarship in chemistry at Queens’ College, Cambridge in 1969. During his studies he switched fields and completed a Ph.D in 1975 in Drosophila developmental cytogenetics with Michael Ashburner (Genetics Dept, Cambridge) and was immediately appointed to a junior faculty position in the department which he held for 5 years. Dr. Richards moved to Strasbourg in 1980 to join Pierre Chambon’s laboratory to learn molecular biology techniques and apply them to his studies of the hormonal regulation of Drosophila development. He used P element transformation extensively for in vivo studies of gene regulation and later developed micro RT-PCR techniques to study multiple transcripts in individual staged/treated Drosophila tissues. He was appointed as a junior group leader in 1982 and has been a senior Research Director of the French CNRS (full Professor) for more than 20 years. He worked in the IGBMC in Strasbourg, an internationally recognized biomedical research institute with 600 members. Dr. Richards joined HFSP in 2004 as Director of Research Grants. Prior to that he spent some 10 years in a dual role as both a scientific group leader at the IGBMC and its Executive Secretary with the overall responsibility for national and international, academic and industrial research contracts including intellectual property issues. In his current role at HFSP he has followed the progress of some 7000 applications to the HFSP international collaborative grant program.

232 Hideki Mizuma received his Master’s degree in Engineering from the Graduate School of Engineering at Hokkaido University in 1983. He joined the Science and Technology Agency (STA) of Prime Minister’s Office in 1983. He has served as Director of Fuel Cycle Research and Development Division of Ministry of Education, Culture, Sports, Science and Technology (MEXT), Director of Regulatory Guides and Review Division, Director of General Affairs Division of Secretariat of Nuclear Safety Commission (NSC) of the Cabinet Office and as a cost free expert to the International Atomic Energy Agency (IAEA) in the Vienna Headquarters. At the IAEA, he acted as a Special Projects Coordinator in the Division of Public Information and SSAC (State System of Accounting for and Control of Nuclear Materials) Training Expert in the Department of Safeguards). Recently, he also served as Director for Science and Technology Research Partnership for Sustainable Development (SATREPS) of Japan Science and Technology (JST). SATREPS is a joint project with the JST and the Japan International Cooperation Agency (JICA), targeting global issues and involving partnerships between principal investigators in Japan and colleagues in developing countries. In April 2014, Hideki Mizuma joined the International Human Frontier Science Program Organization (HFSPO) as Deputy Secretary General.

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234 Universe Evolution and Matter Origin

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

235 Sep 29 (Mon) Special Conference Room

Universe Evolution and Matter Origin

Chair Tatsuya Chujo University of Tsukuba

13:00-13:30 William Trischuk University of Toronto The Discovery of the Higgs Boson with the ATLAS Experiment at CERN

13:30-14:00 Yves Schutz CERN ALICE at LHC: the thermodynamics of strongly interacting matter

Jet Physics in Heavy Ion Collisions: Hard probes of the Quark Gluon 14:00-14:30 Marco van Leeuwen Utrecht University Plasma

Search for invisible decays of a Higgs boson produced in association 14:30-14:50 Hideki Okawa Univesity of Tsukuba with a Z boson in ATLAS

Jet azimuthal distributions with high pT neutral pion triggers in pp 14:50-15:00 Daisuke Watanabe Univesity of Tsukuba collisions √s = 7 TeV from LHC-ALICE

Measurement of direct photon collective flow in √sNN =200GeV AuAu 15:00-15:10 Sanshiro Mizuno Univesity of Tsukuba collisions at RHIC-PHENIX experiment

15:10-15:20 Break Chair Fumihiko Ukegawa University of Tsukuba Current Results and Future Perspectives of Reactor Neutrino 15:20-16:00 Soo-Bong Kim Seoul National Univesity Experiments

16:00-16:40 Ricardo Finger University of Chile Chile, the capital of Observational Astronomy

Experimental search for the cosmic background neutrino decay in the 16:40-17:00 Yuji Takeuchi Univesity of Tsukuba cosmic far-infrared background

17:00-17:20 Dragan Salak Univesity of Tsukuba Bursts of star formation and gas outflows in galaxies

Search for the Standard Model Higgs boson decaying to a bottom- 17:20-17:30 Kenji Kiuchi Univesity of Tsukuba quark pair with the ATLAS detector

Development of Superconducting Tunnel Junction Photon Detector 17:30-17:40 Takuya Okudaira Univesity of Tsukuba with SOI Preamplifier Board to Search for Radiative decays of Cosmic Background Neutrino

17:40 Shinhong Kim Univesity of Tsukuba Closing statement

236

12 / 26 ページ Sep 29 (Mon) Special Conference Room

Universe Evolution and Matter Origin

Chair Tatsuya Chujo University of Tsukuba

13:00-13:30 William Trischuk University of Toronto The Discovery of the Higgs Boson with the ATLAS Experiment at CERN

13:30-14:00 Yves Schutz CERN ALICE at LHC: the thermodynamics of strongly interacting matter

Jet Physics in Heavy Ion Collisions: Hard probes of the Quark Gluon 14:00-14:30 Marco van Leeuwen Utrecht University Plasma

Search for invisible decays of a Higgs boson produced in association 14:30-14:50 Hideki Okawa Univesity of Tsukuba with a Z boson in ATLAS

Jet azimuthal distributions with high pT neutral pion triggers in pp 14:50-15:00 Daisuke Watanabe Univesity of Tsukuba collisions √s = 7 TeV from LHC-ALICE

Measurement of direct photon collective flow in √sNN =200GeV AuAu 15:00-15:10 Sanshiro Mizuno Univesity of Tsukuba collisions at RHIC-PHENIX experiment

15:10-15:20 Break Chair Fumihiko Ukegawa University of Tsukuba Current Results and Future Perspectives of Reactor Neutrino 15:20-16:00 Soo-Bong Kim Seoul National Univesity Experiments

16:00-16:40 Ricardo Finger University of Chile Chile, the capital of Observational Astronomy

Experimental search for the cosmic background neutrino decay in the 16:40-17:00 Yuji Takeuchi Univesity of Tsukuba cosmic far-infrared background

17:00-17:20 Dragan Salak Univesity of Tsukuba Bursts of star formation and gas outflows in galaxies

Search for the Standard Model Higgs boson decaying to a bottom- 17:20-17:30 Kenji Kiuchi Univesity of Tsukuba quark pair with the ATLAS detector

Development of Superconducting Tunnel Junction Photon Detector 17:30-17:40 Takuya Okudaira Univesity of Tsukuba with SOI Preamplifier Board to Search for Radiative decays of Cosmic Background Neutrino

17:40 Shinhong Kim Univesity of Tsukuba Closing statement

237

12 / 26 ページ The Discovery of the Higgs Boson with the ATLAS Experiment at CERN

William Trischuk

Depoartment of Physics, University of Toronto

CERN built the Large Hadron Collider with the express goal of clarifying the source of mass in the Standard Model of particle physics. In the 1960s Brout, Englert, Higgs, and others postulated the addition of a scalar field to the SU(2)xU(1) theory of weak and electromagnetic interactions that would generate the masses of the fundamental bosons and fermions. Their masses would be proportional to their couplings to the “Higgs” field. While elegant, this theory has been around for almost 50 years without any evidence to support the existence of a Higgs boson. Searches at the CERN LEP collider and the Fermilab Tevatron produced only indirect evidence for the Higgs mechanism. It was not until the Large Hadron Collider produced first 7 TeV and later 8 TeV proton-proton collisions that we produced un-equivocal evidence for the existence of a Higgs-like boson. I will describe the Higgs results from the ATLAS experiment from the first period LHC run that took place between 2009 and 2012. After a brief review of the discovery evidence presented in 2012 I will focus on the work that has gone on since to determine whether this new boson is the simplest version, envisaged by Higgs et al., or something more exotic, that might be a harbinger of physics beyond the Standard Model. Preparations are now underway to increase the LHC beam energy to its design, potentially producing 13 TeV proton-proton collisions in early 2015. I will briefly outline some of the things we hope to learn about the Higgs from this new data.

238 ALICE at LHC: the thermodynamics of strongly interacting matter

Yves Schutz

CERN Genève, Switzerland and SUBATECH, Nantes, France

ALICE (A Large Ion Collider Experiment) is among the four large experiments operated at the CERN LHC (Large Hadron Collider) particle-accelerator complex the one dedicated to the heavy-ion scientific program. The scientific objectives of this program are to establish how the strong interaction structures elementary particles to form matter or in other words how the macroscopic properties of QCD (Quantum Chromodynamics, the theory of strong interaction) matter emerge from the first principles that constitute the cornerstones of the Standard Mod- el of particle physics. To tackle this fundamental problem, one explores the phase diagram of nuclear matter in particular in the high temperature sector where matter is predicted to undergo a phase transition from today’s ordinary matter to the phase called QGP (Quark Gluon Plasma), the primordial phase of matter during the early tens of microseconds in the history of the universe. At LHC, ALICE exploits the collisions of heavy ions (presently nuclei of lead accelerated at quasi the speed of light) to heat up matter to extremely high temperatures, well above the critical temperature of the QGP phase transition, and create droplets of primordial matter during a fleetingly short time. Through the detection and identification of the swarm of particles created in every of such collisions and through the detailed study of these collision debris, ALICE attempts to establish the nature and the fundamental properties of the QGP. Following a brief contextual introduction to heavy-ion physics, the empirical approach is discussed illustrated by a few results obtained so far at LHC on the fundamental properties of the QGP.

239 Jet Physics in Heavy Ion Collisions: Hard probes of the Quark Gluon Plasma

Marco van Leeuwen

Nikhef, National Institute for Subatomic Physics and Institute for Subatomic Phsyics, Utrecht University, Netherlands

High-energy nuclear collisions are used to create and study strongly interacting matter at very high energy density in systems that are much larger than the size of the proton (about 1 fm), which is the typical range of the strong force. In the early stages of these collisions, quarks and gluons are expected to be the relevant degrees of freedom, forming a Quark Gluon Plasma. High-energy quarks and gluons (partons) that are produced early in the collision, interact with the Quark Gluon Plasma while propagating outwards and thus provide information about the early stages of the collsion. Experimentally, this process is studied by measuring particle production at large transverse momentum (pT) and by reconstructing jets, which are collimated sprays of particles that originate from high-momentum partons. I will review recent results of such measurements in Pb+Pb collisions with a center-of-mass energy of 2.76 TeV per nucleon pair at the Large Hadron Collider and discuss how they contribute to our understanding of the interactions between a highly energetic parton and the Quark Gluon Plasma and the properties of the Quark Gluon Plasma produced at the LHC.

240 Search for invisible decays of a Higgs boson produced in association with a Z boson in ATLAS

Hideki Okawa on behalf of the ATLAS Collaboration

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

A Higgs boson has been discovered at the ATLAS and CMS experiments with the Run 1 data collected at the Large Hadron Collider (LHC) at CERN (ATLAS Collaboration, Phys. Lett. B 716: 1, 2012; CMS Collaboration, Phys. Lett. B 716: 30, 2012). As the best upper limit on the total decay width of the Higgs boson is still several times larger than the standard model expectation (CMS Collaboration, Phys. Lett. B 736: 64, 2014; ATLAS Collaboration, ATLAS Note, ATLAS-CONF-2014-042, 2014), the presence of beyond-the- standard-model decays of the Higgs boson cannot be excluded. Invisible decays of the Higgs boson to weakly interacting particles such as dark matter are among promising scenarios. A search is performed for evidence of such invisible decays of a Higgs boson produced in association with a Z boson. No deviation from the standard model expectation is observed in 4.5 fb-1 (20.3 fb-1) of 7 (8) TeV pp collision data collected with the ATLAS experiment. Assuming the standard model cross section rate for ZH production, an upper limit of 75%, at the 95% confidence level is set on the branching ratio to invisible-particle decay modes of the Higgs boson at a mass of 125.5 GeV (ATLAS Collaboration, Phys. Rev. Lett. 112: 201802, 2014). The limit on the branching ratio is also interpreted in terms of an upper limit on the allowed dark matter-nucleon scattering cross section within Higgs-portal dark matter scenarios. Limits are also set on an additional neutral

Higgs boson, in the mass range 110

241 Jet azimuthal distributions with high pT neutral pion triggers in pp collisions s = 7 TeV from LHC-ALICE

Daisuke Watanabe

grad. student, University of Tsukuba

242 Measurement of direct photon collective flow in sNN =200GeV AuAu collisions at RHIC-PHENIX experiment

Sanshiro Mizuno

grad. student, University of Tsukuba

243 Current Results and Future Perspectives of Reactor Neutrino Experiments

Soo-Bong Kim

Department of Physics and Astronomy, Seoul National University

Neutrino physics has gone through remarkable progress during the last two decades. A new generation of reactor neutrino experiments measured the last unknown, weakest neutrino mixing angle, so-called theta 13, based on a clear observation of reactor antineutrino disappearance. The exciting result of solving the longstanding puzzle provides a comprehensive picture of neutrino transformation among three kinds of neutrinos. A surprisingly large value of theta 13 has opened up a new window to find the leptonic CP phase angle and the neutrino mass hierarchy, and thus has promoted the next round of neutrino experiments. The reactor experiments have continued data-collection since 2011, to obtain precise measurements of the mixing angle as well as the reactor neutrino flux and spectrum. In this talk, I will present recent results from the three reactor experiments of Daya Bay, Double-Chooz and RENO, and introduce future reactor experiments of JUNO and RENO-50 to determine the neutrino mass ordering.

244 Chile, the capital of Observational Astronomy

Ricardo Finger

Assistant Professor, University of Chile

245 Experimental search for the cosmic background neutrino decay in the cosmic far-infrared background

Yuji Takeuchi1, Shin Hong Kim1, Kenichi Takemasa1, Kenji Kiuchi1, Kazuki Nagata1, Kota Kasahara1, Takuya Okudaira1, Tatsuya Ichimura1, Masahiro Kanamaru1, Kouya Moriuchi1, Ren Senzaki1, Hirokazu Ikeda2, Shuji Matsuura2, Takehiko Wada2, Hirokazu Ishino3, Atsuko Kibayashi3, Satoru Mima4, Takuo Yoshida5, Shota Komura5, Keishuke Orikasa5, Ryuta Hirose5, Yukihiro Kato6, Masashi Hazumi7, Yasuo Arai7, Erik ramberg8, Jonghee Yoo8, Mark Kozlovsky8, Paul Rubinov8, Dmitri Sergatskov8, Soo-Bong Kim9

1Institute of Physics, University of Tsukuba 2Institute of Space and Astronautical Science, JAXA 3Okayama University 4RIKEN 5University of Fukui 6Kinki University 7High Energy Accelerator Research Organization, KEK 8Fermi National Accelerator Laboratory 9Seoul National University

We present a proposal for an experiment to search for the cosmic background neutrino decay in the cosmic far-infrared background, and discuss the feasibility of the application of Superconducting Tunnel Junction (STJ) detectors to the experiment as far-infrared single photon detector. Due to the mixing between the different mass generations of the neutrino, a heavier neutrino is expected to decay to a lighter neutrino with a photon, and the cosmic background neutrino (CνB) is predicted as a relic of the big bang, while neither of the neutrino decay nor the CνB is confirmed experimentally yet. The photon energy spectrum from the neutrino radiative decays in the CνB is expected to have a sharp edge at high energy end in a far-infrared region ranging from 14meV to 25meV (from 50um to 90um in wavelength). We explore the cosmic infrared background photon energy spectrum in this region for feeble contribution from neutrino decays. Thus, the detector is required to measure photon-by-photon energies with high resolution enough to identify the edge structure, as well as to be designed for a rocket or satellite experiment. One of promising choices for the detector is STJ using hafnium (Hf-STJ) which is expected to have 2% energy resolution for single photon of 25meV due to very small superconducting gap energy of hafnium. Another choice for the detector is a combination of a diffraction grating and an array of niobium-aluminum STJ (Nb/Al-STJ) pixels, where each the Nb/Al-STJ pixel is capable of single photon detection for a far-infrared photon delivered to each pixel according to its wavelength by the grating. By a 200-second measurement with these detectors if successfully implemented, we expect the detection of neutrino decays in the CνB for the neutrino lifetime up to the order of 1014 years.

246 Bursts of star formation and gas outflows ingalaxies

Dragan Salak

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

Stars in galaxies are formed in molecular clouds. Massive stars blow stellar winds and explode as supernovae thereby returning most of the baryons back to the interstellar medium (ISM). The material then becomes fuel for further star formation and the cycle can be sustained over ~109 years. By contrast, in starburst galaxies, stars are formed at a furious rate, which leads to rapid consumption of molecular gas. Newly formed massive stars provide strong feedback on the ambient ISM: radiation pressure and supernova explosions. The energy of the feedback is high enough for a superwind to form: large-scale outflow of gas and dust from the starburst region that restricts further star formation. In this talk, I present recent observations of M82, an archetypal superwind galaxy. Due to proximity (3.5 Mpc) and peculiar starburst nucleus, M82 is one of the best-studied galaxies. Our observations of molecular gas traced with CO (J=1-0) revealed that molecular gas clouds are ejected up to >3 kpc above the galactic plane. At the base of the outflow is a 300-pc molecular-gas ring. Molecular gas is ejected from the nuclear ring in two prominent expanding shells and filaments. The mass outflow rate is comparable to the star formation rate (10-20 Msun/yr). We show that the kinetic energy of the outflow can be provided from radiation pressure and supernova explosions. With current starburst activity in the nuclear ring, molecular gas may be consumed within ~107 years hence suppress further star formation.

247 Search for the Standard Model Higgs boson decaying to a bottom-quark pair with the ATLAS detector

Kenji Kiuchi

grad. student, Univesity of Tsukuba

248 Development of Superconducting Tunnel Junction Photon Detector with SOI Preamplifier Board to Search for Radiative decays of Cosmic Background Neutrino

Takuya Okudaira

grad. student, Univesity of Tsukuba

249 NOTE

250 Symposium for Food Security and Sustainable Agriculture

Food Security Research Unit, University of Tsukuba Graduate School of Life and Environmental Sciences, University of Tsukuba

251 Sep 29 (Mon) 5C216

Symposium for Food Security and Sustainable Agriculture

13:30-13:40 Miyako Kusano University of Tsukuba Brief Introdution

Chair Miyako Kusano University of Tsukuba Metabolomic Discoveries 13:40-14:10 Nicolas Schauer Comprehensive Metabolomics to Study Flavour in Natural Food GmbH

Agricultural Biotechnology Exploring thermotolerance diversity in plants in the context of global 14:10-14:40 Yee-yung Charng Research Center, Academia warming Sinica

RIKEN Center for Sustainable 14:40-15:10 Satoko Yoshida Molecular and genomic analyses of the witchweed Striga Resource Science

15:10-16:00 Alain Blanchard University of Bordeaux Building minimal cellular chassis using synthetic biology

16:00-16:20 Coffee Break Chair Yasuhiro Ishiga University of Tsukuba Distribution of Rhytismataceous fungi on Camellia japonica leaves in 16:20-16:35 Kimiyo Matsukura University of Tsukuba Japan

Characterization and evaluation of F1 hybrid lines with SlETR1 mutant 16:35-16:50 Syariful Mubarok University of Tsukuba alleles

Molecular phylogenetic and morphological approach for species level 16:50-17:05 Yuho Ando University of Tsukuba of the Grosmannia piceiperda complex

17:05-17:20 Takuya Uehara University of Tsukuba Identification of novel sex pheromone component in

17:20-17:30 Yuichi Yamaoka University of Tsukuba Closing Statement

252

18 / 26 ページ Sep 29 (Mon) 5C216

Symposium for Food Security and Sustainable Agriculture

13:30-13:40 Miyako Kusano University of Tsukuba Brief Introdution

Chair Miyako Kusano University of Tsukuba Metabolomic Discoveries 13:40-14:10 Nicolas Schauer Comprehensive Metabolomics to Study Flavour in Natural Food GmbH

Agricultural Biotechnology Exploring thermotolerance diversity in plants in the context of global 14:10-14:40 Yee-yung Charng Research Center, Academia warming Sinica

RIKEN Center for Sustainable 14:40-15:10 Satoko Yoshida Molecular and genomic analyses of the witchweed Striga Resource Science

15:10-16:00 Alain Blanchard University of Bordeaux Building minimal cellular chassis using synthetic biology

16:00-16:20 Coffee Break Chair Yasuhiro Ishiga University of Tsukuba Distribution of Rhytismataceous fungi on Camellia japonica leaves in 16:20-16:35 Kimiyo Matsukura University of Tsukuba Japan

Characterization and evaluation of F1 hybrid lines with SlETR1 mutant 16:35-16:50 Syariful Mubarok University of Tsukuba alleles

Molecular phylogenetic and morphological approach for species level 16:50-17:05 Yuho Ando University of Tsukuba taxonomy of the Grosmannia piceiperda complex

17:05-17:20 Takuya Uehara University of Tsukuba Identification of novel sex pheromone component in Lepidoptera

17:20-17:30 Yuichi Yamaoka University of Tsukuba Closing Statement

253

18 / 26 ページ Comprehensive Metabolomics to Study Flavour in Natural Food

Nicolas Schauer

Metabolomic Discoveries GmbH, Potsdam, Germany

Flavour analysis has been thus far principally a matter of sensory profiling by experts or consumers. Products are being assessed on taste, aroma and texture based on the frame of reference of the taste panel. Although sensory profiling provides very valuable information for product development or the monitoring of product quality, it does not provide an objective and complete picture of the whole complexity of compounds that determine flavour. A relatively new way of analyzing flavour is through metabolomics. This technology gives an unbiased and most comprehensive analysis of the biochemical or metabolic state of a sample. Here, we have developed a platform, the Flavor Profiler™, which combines a multi-parallel analytical approach with high-performance computing pattern identification and modelling of flavour. This allows to identify flavour relevant compounds and model optimal flavour compositions. It further allows to control and ensure flavour quality in an objective way.

254 Exploring thermotolerance diversity in plants in the context of global warming

Yee-yung Charng, Hsiang-chin Liu, Wei-di Wang, Kuo-hsing Chai and Yu-ting Juan

Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan

Temperature fluctuates dynamically in the natural environment. Elevations in temperature of different intensity and duration result in different types of heat stress in plants. For example, the effect induced in plants by acute heat stress associated with brief exposure to extremely high temperature is different from that induced by chronic heat stress caused by prolonged exposure to moderately high temperature; not withstanding, both these types of stress could lead to death if the tolerance threshold is exceeded. Being mostly sessile during their life cycle, plants have apparently evolved mechanisms to adapt to different types of heat stress; however, the details of these adapative mechanisms are not clear. In this presentation, I will cover recent progress in functional genomic studies that indicate that plants have evolved diverse thermotolerance responses for different heat stress regimes. These responses include basal thermotolerance, short-term and long-term acquired thermotolerance, and thermotolerance to moderately high temperatures. Distinguishing between these different types of thermotolerance is important to increase understanding of how plants respond to heat stress in the natural environment. Phenotyping of genetic mutants with thermotolerance assays that address the distinct responses is one strategy through which the genes required for tolerance to specific heat stress regimes can be identified. Genes encoding proteins involved in various biological functions including transcription, translation, molecular chaperoning, protein degradation, RNA stability, lipid metabolism, chromatin modulation, and posttranslational modification have been shown to form a complex thermotolerance network. In the context of global warming, it is critical to know how plants adapt to climate change by coarse- or fine-tuning of the components in this network. Understanding of diversity in thermotolerance and its underlying mechanisms may facilitate the breeding of heat tolerant crops that can better adapt to a changing climate.

255 Molecular and genomic analyses of the witchweed Striga

Satoko Yoshida and Ken Shirasu

RIKEN Center for Sustainable Resource Science, Japan

The parasitic plant Striga spp (common name, witchweed) is a major constrain in African agriculture. Striga parasitize economically important crops such as maize, sorghum and rice and suck their nutrients and water up. The host plants are severely affected in their growth and yields and the losses caused by Striga are estimated as much as 1 billion USD. However, the molecular mechanisms of Striga parasitism are not well understood and effective management methods have not been established. Striga is an obligate parasite and therefore has a unique life cycle. The germination requires host-derived strigolactones, which have also been characterized as host symbiotic signals for arbuscular mycorrhizal fungi in addition to their role as endogenous plant hormones that regulate various developmental processes. The germinated Striga seedlings form an invasive organ called a haustorium. The haustorium penetrates into a host root and eventually establishes vascular connections with its host. Aiming to understand the molecular mechanisms of Striga parasitism, we have performed genome and transcriptome analyses. Complete genome of S. asiatica was sequenced and predicted genes were annotated. The genome features, such as GC contents and frequency of repeat elements, are similar to autotrophic plants. Striga genome contains evidences of horizontal gene transfers from host plants. Transcriptome analysis revealed that genes harboring hydrolase activities are up-regulated during host invasion, suggesting active degradation of cellular components. For further characterization of genes involved in parasitism, we have developed a model system using a Japanese native facultative parasite, Phtheirospermum japonicum, which facilitate in vivo functional analyses of parasite genes.

256 Building minimal cellular chassis using synthetic biology

Alain Blanchard, Pascal Sirand-Pugnet, Carole Lartigue

University of Bordeaux, France UMR1332 Fruit Biology and Pathology, INRA, France

Synthetic biology (SB) is a key enabling technology with the potential to fundamentally change the approach, tools and techniques of modern biological research and innovation, to the benefit of the bioeconomy and society as a whole1. SB is the engineering and/or the design of biological systems that do not already exist in the natural world. It includes a number of complementary approaches such as the building of minimal cells, the metabolic engineering of existing cells for biotechnological purposes, the assembly of bio-components into proto- cells and the use of modified biochemicals to create artificial genetic systems. The concept of minimal cell has attracted much attention in past years as it offers the possibility to understand the functioning of all DNA-encoded elements that are necessary to support life, at least in the laboratory. To reach this goal, it is logical to start with a living organism, which through the course of streamlining evolution, came to resemble a minimal cell. Arguably bacteria belonging to the genus Mycoplasma are among the best candidates for this purpose and have been used as starting material to develop SB technologies in order to manipulate their cell components on a large scale. In our laboratory, using mycoplasma cells we are pursuing the development of technologies with the aim of obtaining different cellular chassis that fulfill various applications. A prerequisite to the building of a cellular minimal chassis is the identification of the genome components that are able to support life. By using comparative genomics, we have shown that there are different minimal sets of genes to support complex and essential functions such as the synthesis of proteins. This chassis once obtained will be modified by plugging-in heterologous sets of genes to deliver products in different environments.

1: ERASynBio strategic vision; https://www.erasynbio.eu/lw_resource/datapool/_items/item_59/erasynbiostrategicvision.pdf

257 Distribution of Rhytismataceous fungi on Camellia japonica leaves in Japan

Kimiyo Matsukura1, Yuichi Yamaoka1, Maiko Kagami2, Takashi Osono3 and Yasuhiro Ishiga1

1Faculty of Life and Environmental Sciences, University of Tsukuba, Japan 2Faculty of Science, Toho University, Japan 3Center for Ecological Research, Kyoto University, Japan

Pathogen outbreaks in important crop plants could give a significant impact on human life. For example, the outbreak of soybean rust and wheat stem rust impacted the economy all over the world in recent years. Therefore, it is important to understand the fungal distribution and factors affecting it for sustainability of agriculture and ecosystem. Rhytismataceae is a common family known as endophytic, parasitic and saprotrophic fungi associated with various plants. Rhytismataceous fungi on Camellia japonica are known as primary selective decomposers for lignin after colonizing, and also isolated from living leaves as endophytes. However, the distribution of these fungi in Japan and possible factors affecting the distribution are still unknown. In this study, we investigated the distribution of Rhytismataceous fungi on C. japonica leaf litter across Japan. The distribution analysis revealed that there were three Rhytismataceous fungi (Coccomyces sp., Lophodermium jiangnanense and Rhytismataceae sp.) on C. japonica leaves in Japan. Coccomyces sp. distributed all sites investigated broadly, whereas L. jiangnanense was restricted in southwestern region that was characterized by much precipitation and high temperature in early summer. Rhytismataceae sp. localized around Kanto district in warm-temperate zone. Coccomyces sp. was most abundant among three species in most of sites, excluding where L. jiangnanense colonized abundantly. On the other hand, L. jiangnanense and Rhytismataceae sp. were detected from living leaves at sites where they have not formed fruiting body on litter by PCR methods using species-specific primers. These results suggest that Rhytismataceous fungi might show different distribution patterns on living leaves. Further analyses for distribution patterns of Rhytismataceous fungi on leaf litter and living leaves, are needed to estimate the possible factors affecting their distribution.

258 Characterization and evaluation of F1 hybrid lines with SlETR1 mutant alleles

Mubarok S, Y. Okabe, T. Ariizumi, N. Fukuda and H. Ezura

Graduate School of Life and Environmental Sciences, University of Tsukuba, Japan

Fruit shelf life is one of the most important characters for breeding program that is regulated by ethylene. Control ethylene perception by modifying the ethylene receptor would be a possible method for improving shelf life of tomato fruits. Two Sletr1 tomato mutant alleles, Sletr1-1 and Sletr1-2, with a mutation in the ethylene receptor gene (SlETR1) have been isolated in our previous study. Those mutants showed reduced ethylene sensitivity and extended fruit shelf life that is expecting the potential as a breeding material. This study aimed to characterize and evaluate fruit quality of F1 hybrid lines from two Sletr1 mutant alleles. Those mutants and the wild type, Micro-Tom as control were crossed with four commercial pure line cultivars (‘Aichi First’, ‘Ailsa Craig’, ‘Money Maker’ and ‘M82’) to obtain F1 hybrid lines that would be evaluated. Sletr1-1 was not appropriate for breeding material because its F1 hybrid lines showed strong ethylene insensitivity and high sensitivity to biotic and abiotic stress, whereas Sletr1-2 would be potential for breeding material. Fruit of Sletr1-2 F1 hybrid lines delayed in the ripening process and the shelf life was improved 4 – 5 days longer depend on genetic background of its pure line cultivars. In other characters, there are no significant effect of Sletr1-2 mutation on vegetative and generative plant characters, fruit size, ethylene production and respiration rate of harvested fruits. However it shows significant effect on fruit color, fruit firmness, carotenoid content, and organic acid content at the harvesting time. These results indicate the potential Sletr1-2 mutant as a breeding material to develop new cultivar with improved fruit shelf life.

259 Molecular phylogenetic and morphological approach for species level taxonomy of the Grosmannia piceiperda complex

Yuho Ando1, Hayato Masuya2, Riikka Linnakoski3, Z. Wilhelm de Beer4, Michael J. Wingfield4, and Yuichi Yamaoka1

1Faculty of Life and Environmental Sciences, University of Tsukuba, Japan 2Tohoku Research Center, Forestry and Forest Products Research Institute (FFPRI), Japan 3Department of Forest Sciences, University of Helsinkii, Finland 4Department of Microbiology, Forestry and Agricultural Biotechnology Institute (FABI), University of Pretoria, South Africa

The control of plant diseases has risen to become one of the most important issues for global food security and sustainable agriculture. The taxonomy of plant pathogenic organisms with correct identification is critical aspect of disease control. The genusLeptographium sensu lato (Ophiostomatales, Ascomycota) is characterized by black ascomata, sheathed ascospores, and dark erect conidiophores giving rise to series of branches bearing conidiophores with conidia produced in slimy masses. Most species in this genus cause sap stain of conifer timber and are vectored by bark beetles. Phylogenetic studies have revealed nine species complexes in Leptographium s. l. One of these, the Grosmannia piceiperda complex, currently accommodates four species, but a recent multigene study has revealed seven lineages in the complex. The aim of this study was to resolve species boundaries in the complex using reference isolates of the known species from the USA and Eurasia, and including Japanese isolates. The results of phylogenetic analyses based on the ITS-LSU regions, as well as parts of the β-tubulin, EF-1α, and actin genes, showed eleven well supported lineages in the G. piceiperda complex. No authentic isolates are available for G. piceiperda and G. europhioides, both originally described from Canada. However, one lineage including only USA isolates most likely represents one of these two species. The second lineage included only European isolates and clearly represents an undescribed species. The Japanese isolates separated into eight lineages, including G. aenigmatica, G. laricis, and apparently six new lineages, one of which included isolates from Russia. In this way, the lineages of G. piceiperda complex were showed tendency that these lineages were separated by association of intercontinental and conifer genus.

260 Identification of novel sex pheromone component in Lepidoptera

Takuya Uehara1,2, Hideshi Naka3, Shigeru Matsuyama4, Tetsu Ando5 and Hiroshi Honda4

1Graduate School of Life and Environmental Sciences, University of Tsukuba, Japan 2Research Fellow of the Japan Society for the Promotion of Science 3Faculty of Agriculture, Tottori University, Japan 4Faculty of Life and Environmental Sciences, University of Tsukuba, Japan 5Graduate School of Bio-Applications and Systems Engineering, Tokyo University of Agriculture and Technology, Japan

In order to clarify how species specificity of sex pheromones develops in the process of speciation, we have determined the sex pheromones from 17 species of hawk . Most of these sex pheromones consist of C16 unsaturated aldehydes, 11-hexadecenals and 10,12-hexadecadienals (Uehara et al. 2012). Interestingly, one species, tancrei uses C15 dienyl aldehyde, (9E,11Z)- and (9Z,11Z)-9,11-pentadecadienals (Uehara et al. 2013). D. tancrei commonly occurs in Japan and is a sporadic pest of Oleaceae ornamental plants including sweet osmanthus, sweet scented , and privet. Larvae of the were collected from privet, (Lamiales, Oleaceae) and reared in a laboratory condition until their pupation. After emergence, female pheromone glands were extracted with distilled hexane, and then the extracts were subjected to Gas Chromatography– Electroantennograhic Detection (GC-EAD), Gas Chromatography–Mass Spectrometry (GC-MS), and gas chromatography (GC) analyses. GC-EAD analyses showed that the male antenna responded to two components in the crude pheromone extracts. GC-MS analysis determined these two components to be pentadecadienals. GC-MS of their MTAD derivatives showed conjugated double bonds at the 9- and 11-positions, indicating 9,11-pentadecadienals. Geometrical isomers of these candidates were determined based on comparison of their Kovats retention indices with those of synthetic compounds. Field bioassays with four isomers of 9,11-pentadecadienal and their mixtures confirmed that the two sex pheromone components of D. tancrei are (9E,11Z)-9,11-pentadecadienal and (9Z,11Z)-9,11-pentadecadienal with the highest male catches observed for a 90:10 ratio. This is the first report of ,911-pentadecadienals as sex pheromone components in lepidopteran species.

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262 Initiatives of Research, Preservation and Management for Granting UNESCO World Heritage Status at the Pyu and Bagan Monument

World Heritage Studies, Graduate School of Comprehensive Human Sciences, University of Tsukuba

263 Sep 30 (Tue) Meeting Room 5

Initiatives of Research, Preservation and Management for Granting UNESCO World Heritage Status at the Pyu and Bagan Monument

Moderator Junko Okahashi University of Tsukuba

9:00-9:05 Junko Okahashi University of Tsukuba Brief Introduction

Field School of Archaeology Challenges for the future at the World Heritage inscribe site, Pyu 9:05-10:05 U Win Kyaing (Pyay) Ancient Cities

10:05-11:05 Kai Weise UNESCO Issues on the safeguarding of Bagan monuments

11:05-11:35 Ichita Shimoda University of Tsukuba Conservation of the architectural heritages in the Southeast Asia

Discussion U Win Kyaing, 11:35-12:05 Kai Weise, Nobuko Inaba, Ichita Shimoda

12:00-12:20 Questions from the floor

12:20-12:25 Nobuko Inaba University of Tsukuba Summary

264

19 / 26 ページ Sep 30 (Tue) Meeting Room 5

Initiatives of Research, Preservation and Management for Granting UNESCO World Heritage Status at the Pyu and Bagan Monument

Moderator Junko Okahashi University of Tsukuba

9:00-9:05 Junko Okahashi University of Tsukuba Brief Introduction

Field School of Archaeology Challenges for the future at the World Heritage inscribe site, Pyu 9:05-10:05 U Win Kyaing (Pyay) Ancient Cities

10:05-11:05 Kai Weise UNESCO Issues on the safeguarding of Bagan monuments

11:05-11:35 Ichita Shimoda University of Tsukuba Conservation of the architectural heritages in the Southeast Asia

Discussion U Win Kyaing, 11:35-12:05 Kai Weise, Nobuko Inaba, Ichita Shimoda

12:00-12:20 Questions from the floor

12:20-12:25 Nobuko Inaba University of Tsukuba Summary

265

19 / 26 ページ Initiatives of Research, Preservation and Management for Granting UNESCO World Heritage Status at the Pyu and Bagan Monument

Kai Weise, UNESCO (Keynote Speech/Discussion) U Win Kyaing, Field school of Archaeology (Pyay) (Keynote Speech/Discussion) Inaba Nobuko (Discussion) Shimoda Ichita (Report, Discussion) Okahashi Junko (Moderator)

Many countries including the neighboring ASEAN region are strongly interested in the international cooperation to Republic of the Union of Myanmar which is seeing the prospect of democracy and accelerated the economic development in recent years. In June this year, one of the significant archaeological site, Pyu Ancient Cities was inscribed to the UNESCO World Heritage site that is the Myanmar’s first inscribed site to the List. Three archaeological sites, Halin, Beikthano and Sri Ksetra are located along the Ayeyarwady river and flourished from 2nd to 9th century as the capital city of the Pyu Empire. There are numerous archaeological remains include excavated palace citadels, burial grounds and early industrial production sites, as well as monumental brick Buddhist stupas, partly standing walls and water management features that underpinned the organized intensive agriculture. Subsequently, the Myanmar government is expected to begin in earnest to prepare for the next World Heritage application of Bagan Monuments. Bagan monument is sometime referred as one of the three greatest Buddhism sites in the world, with Angkor monuments in Cambodia and Borobudur temple in Indonesia. Several thousands of brick structures were constructed mainly from 11th to 13th century, and still maintain the highest historical valuable sites in Myanmar from architectural, artistic and landscape points of view. In addition, this site is inheriting the practice of this unique region. This site was attempted to be inscribed as a UNESCO World Heritage in 1990s, but they were interrupted this first challenges. While a rapid increase of tourists in the past few years, pressure and expectations of tourism development increases, it is assumed to ensure the value of the ruins, and comprehensive approach towards the maintenance has been required. In this session, two of the significant person who involved in the preservation and cultural development work in these sites will lecture the direction of the international cultural cooperation including government and UNESCO projects on the research, restoration, and sustainable development. Then, we discussed the issues on the current state of the preservation management including some case studies of archaeological sites in Southeast and South Asia, and clarify the needs of the further research, conservation, sustainable development, and international cooperation for the future.

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268 Symposium on Health and Sport Sciences

Faculty of Health and Sport Sciences, University of Tsukuba

269 Sep 30 (Tue) 5C216

Symposium on Health and Sport Sciences

9:00-9:05 Michiyoshi Ae University of Tsukuba Opening statement

(1) Biomechanics / Sports Technology Chair Michiyoshi Ae University of Tsukuba University of Southern Improving the Biomechanics of Aerial Skills performed by Olympic 9:05-9:40 Jill L. Mcnitt-Gray California Athletes

Research and Development of Sport Equipments at the University of 9:40-10:15 Takeshi Asai University of Tsukuba Tsukuba

Sports technology and performance; how athletes of all standards can 10:15-10:50 Andy Harland Loughborough University benefit

10:50-11:10 Coffee Break (2) Health Science Chair Seiji Maeda University of Tsukuba A novel fall- and dementia-exercise program for successful aging of 11:10-11:45 Tomohiro Okura University of Tsukuba older adults

Application of Korean Red Ginseng or Some Specific Ginsenosides 11:45-12:20 Hyon Park Kyung Hee University as a Nutritional Ergogenic

12:20-12:25 Akira Nakagawa University of Tsukuba Closing statement

270

25 / 26 ページ Sep 30 (Tue) 5C216

Symposium on Health and Sport Sciences

9:00-9:05 Michiyoshi Ae University of Tsukuba Opening statement

(1) Biomechanics / Sports Technology Chair Michiyoshi Ae University of Tsukuba University of Southern Improving the Biomechanics of Aerial Skills performed by Olympic 9:05-9:40 Jill L. Mcnitt-Gray California Athletes

Research and Development of Sport Equipments at the University of 9:40-10:15 Takeshi Asai University of Tsukuba Tsukuba

Sports technology and performance; how athletes of all standards can 10:15-10:50 Andy Harland Loughborough University benefit

10:50-11:10 Coffee Break (2) Health Science Chair Seiji Maeda University of Tsukuba A novel fall- and dementia-exercise program for successful aging of 11:10-11:45 Tomohiro Okura University of Tsukuba older adults

Application of Korean Red Ginseng or Some Specific Ginsenosides 11:45-12:20 Hyon Park Kyung Hee University as a Nutritional Ergogenic

12:20-12:25 Akira Nakagawa University of Tsukuba Closing statement

271

25 / 26 ページ Improving the Biomechanics of Aerial Skills performed by Olympic Athletes

Jill L. McNitt-Gray, PhD, FASB

Departments of Biological Sciences and Biomedical Engineering University of Southern California, Los Angeles, CA

Satisfying mechanical objectives of sports-specific tasks requires effective interaction be- tween the neuromuscular system, the musculoskeletal system and the environment. Analysis of complex aerial skills, such as those requiring the generation of linear and angular momen- tum, indicates that the nervous system organizes the human body into a number of operational subsystems that are coordinated according to priorities specific to the individual performer. By determining multi-joint control strategies used by elite athletes across different tasks, we can advance our understanding of the biomechanics and facilitate learning and improvements in performance. The acquisition of evidence for modifications in movement technique requires systematic experimentation conducted in realistic contexts, including the Olympic Games. The combination of laboratory-based experimentation and dynamic modeling with evidence from field-based studies allows us to determine how athletes are generating the forces causing the observed movements and ascertain why certain factors affect performance. These quan- titative results acquired under realistic conditions can then be used as a basis for designing skill progressions used to improve performance for athletes at all skill levels. As part of this talk, we will discuss how knowledge of flight and contact phase biomechanics can be used to improve the performance of Olympic level divers and gymnasts during competition.

272 Research and Development of Sport Equipments at the University of Tsukuba

Takeshi Asai, Norihisa Fujii, Sekiya Koike, Michiyoshi Ae

Faculty of Health and Sport Sciences, University of Tsukuba, Japan

Research projects related to sport fluid engineering are being conducted at the University of Tsukuba, as a part of the ‘Multi-support Project’, sponsored by Ministry of Education, Cul- ture, Sports, Science and Technology, Japan. For example, research and development related to bicycle competitions, including the areas of competitive bicycle frames, wheels, helmets, and wear, have been conducted jointly with many affiliated companies. The sport wind tunnel at the University of Tsukuba has been used to examine the aerodynamic characteristics of sport products, in order to improve the perform- ance of competitive bicycles. In the case of competition wear, examinations include ways to delay the boundary layer separation on the back surface of an athlete, the turbulence effects on the lower body caused by pedalling, and the rectification of the air flow from the stomach region to the back, and findings have been implemented. In addition, in the research and development for ski jump suits, the fabric resistance of ski jump wear was measured using an airfoil tool, and a full scale mannequin was used to analyze the aerodynamic characteristics of ski jump suits, while taking into consideration the forms and sewing portions of the latest ski jump suits. Furthermore, computational fluid dynamics was employed to analyze the flow velocity distribution and pressure distribution of an athlete during flight phase of ski jump, for the purpose of improving ski jump suits. The developed ski jump suits were worn by all the Japanese athletes who participated in the 2014 Winter Ol- ympics at Sochi in Russia, where the ski jump team won a silver medal (men’s individual large hill) and bronze medal (men’s team large hill), and the Nordic combined team won a bronze medal.

273 Sports technology and performance; how athletes of all standards can benefit

Andy Harland

Director, Sports Technology Institute, Loughborough University, UK

Technology plays an ever increasing role in sport, from training and conditioning aids, through enhanced equipment used in competition to performance analysis and feedback systems. In his talk Dr Harland will reflect on recent technological developments in sport and discuss how these have affected sports performance. He will consider the role that technology might play in future and explore the boundaries between technological advantage and unfair advantage. Drawing on case studies from his own group’s research, Dr Harland will discuss how partnership based, athlete centered approaches to research have led to successful outcomes in a range of individual and team sports. He will also discuss how the public appetite for technology is important in driving advances in sports technology and how the needs of elite athlete compare to those of recreational athletes and why it is important to consider both.

274 A novel fall- and dementia-exercise program for successful aging of older adults

Tomohiro OKURA, PhD

Faculty of Health and Sport Sciences, University of Tsukuba

To prevent physical frailty and a decline in cognitive function in older adults, regular physical activity and exercise training are considered indispensable. We have developed a novel exercise program for preventing falls and dementia called “Square-Stepping Exercise” (SSE), which can induce functional activation of the brain. The purpose of this study was to investigate the longitudinal effect on the physical and cognitive functions of community-dwelling, older, Japanese adults who regularly performed the SSE over 3 years. Our study had 2 groups: the SSE Group (n=40; mean age 70.2±3.6 years) in which par- ticipants voluntarily continued the SSE program once or twice per week for 3 years, and the Control (C) Group (n=40; mean age 70.1±3.6 years) who were randomly selected from the basic resident register. We evaluated physical performance with 7 performance tests and assessed cognitive function using the 5-cog test. In the SSE Group, results of the 5-repetition sit-to-stand (SIS) and timed up-and-go (TUG) tests improved significantly over 3 years (SIS: 7.0 to 6.4 sec; TUG: 5.7 to 5.4 sec, trend P<0.05). On the other hand, no changes were observed in the C Group. There were also significant differences between the two groups when we look at the change in SIS and TUG results from year 2 to year 3: SIS (2nd year: 5.8 vs. 7.2 sec; 3rd year: 6.4 vs. 7.2 sec, P < 0.05) and TUG (2nd year: 5.1 vs. 5.7 sec; 3rd year: 5.4 vs. 5.9 sec, P<0.05) (SSE Group vs. C group, respectively). Furthermore, 5-cog test scores in the SSE Group increased significantly over 3 years while no change was observed in the C Group (SSE 69.7 to 84.1, P<0.05; C 69.3 to 76.3, not significant). The scores of the 5-cog test indicated a significant difference in the third year between the SSE and C groups (84.1 vs. 76.3 points, P<0.05). These results suggest that regular and voluntary participation in SSE by older adults over three years could help them maintain or improve their physical and cognitive functions.

275 Application of Korean Red Ginseng or Some Specific Ginsenosides as a Nutritional Ergogenic

Hyon Park, Ph.D.

Professor at the Department of Sports Medicine, Kyung Hee University, Korea

Ginseng, which is often called the root of life, is a deciduous perennial plant which has a very long history of use for the promotion of health, especially in far eastern countries and in Europe. From 11 ginseng species, Korean ginseng is known to be the highest-quality one that contains the largest variety of ginsenosides, efficacy components of ginseng, as around 32 out of 37 known ginsenosides so far. A processed form as of red ginseng is the popular product in the market, and its Korean FDA certified efficacies are as follows; 1) enhances the immune system, 2) aids in recovery from fatigue, 3) promotes blood circulation, and 4) promotes memory functions. Other studies on Korean ginseng have proposed additional efficacies: control over blood sugar level and vast improvement on male sexual function. Korean red ginseng or other purified ginsenosides as Rg1, Rg3, Rb1, and Rh1, have been tested as an ergogenic for athletic performance for decades. Effects on the attenuation of negatives caused by lipid-peroxidation, the increase of immune function, and the ability of faster recovery from severe physical activity are agreed in most of studies on animals and human subjects. On the other hand, supporting evidences of performance improvement have not produced enough result to be accepted yet, but some results of possible beneficial effects of specific purified ginsenosides on physical performance have been shown in several recent well- designed(randomized, double-blind, placebo-controlled, and crossover) studies. Proposed mechanism of effects involves several biochemical processes of oxidative stress buffering and anti-inflammatory works of applied ginsenosides. We still need to look deeper on ginseng and its efficacy components, ginsenosides, on optimum dose, types, and timing to use them as safe and recommendable nutritional ergogenic supplements. This presentation will cover from the general information of ginseng to the application of ginseng as an ergogenic with various scientific evidences.

Key words ; Korean red ginseng, ginsenosides, health, physical performance, ergogenics

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278 Symposium for expanding application of new power semiconductor devices

Power Electronics Laboratory, Graduate School of Pure and Applied Sciences, University of Tsukuba

279 Sep 30 (Tue) Meeting Room 6

Symposium for expanding application of new power semiconductor devices

Chair Noriyuki Iwamuro University of Tsukuba Norwegian University of 13:00-14:30 Marta Molinas Power Electronics in the Modern Power System Science and Technology

Norwegian University of Challenges for Operation and Control of Grid Connected Power Jon Are Suul Science and Technology Converters

14:30-15:00 Discussion

Hiroshi Tadano University of Tsukuba Closing statement

280

22 / 26 ページ Sep 30 (Tue) Meeting Room 6

Symposium for expanding application of new power semiconductor devices

Chair Noriyuki Iwamuro University of Tsukuba Norwegian University of 13:00-14:30 Marta Molinas Power Electronics in the Modern Power System Science and Technology

Norwegian University of Challenges for Operation and Control of Grid Connected Power Jon Are Suul Science and Technology Converters

14:30-15:00 Discussion

Hiroshi Tadano University of Tsukuba Closing statement

281

22 / 26 ページ Power Electronics in the Modern Power System

Marta Molinas

Department of Engineering Cybernetics, Norwegian University of Science and Technology, 7495 Trondheim, Norway

The use of power electronics in power systems has for long time been increasing due to the widespread application of electric drives and switch mode power supplies. More recently, this trend has been accentuated with the grid integration of renewable energy sources which due to their basic incompatibility with the grid requirements has introduced new challenges. In this context, power electronics enables a very effective, flexible and active coupling with the grid system offering high controllability and buffering capabilities (e.g. energy storage). Simultaneously, the range of applications of power electronics has been moving beyond the domains of generation and traditional loads, migrating into compensation devices (FACTS), actively controlled loads, harmonic filters, DC circuit breakers, electronic transformer, HVDC, energy storage and transportation in the form of moving loads in the system. When this pervading presence of power electronics combines with other features such as nonlinear time- varying loads and equipment in modern power system, the new properties introduced by the cybernetic nature of power electronics are defining the overall behavior of the system, making it an increasingly complex issue. The presentation will cover aspects of the new dimension that the pervasive use of power electronics is introducing in modern power systems, highlight research findings in some of the above areas, and conclude with the identification of new avenues for research triggered by the many challenges of the new scenario.

282 Challenges for Operation and Control of Grid Connected Power Converters

Jon Are Suul1,2

1Department of Electric Power Engineering, Norwegian University of Science and Technology, Norway 2SINTEF Energy Research, Norway

The utilization of actively controlled Power Electronic Converters for grid connected applications is continuously increasing, expanding into a wide range of power and voltage levels. In addition to distributed generation units like wind turbines and photovoltaic generation systems where power electronic converters are necessary for grid integration, loads, transmission schemes and energy storage units are also increasingly utilizing actively controlled converters as their grid interface. As the penetration of power electronic converters in the power system is increasing, it is expected that they will meet stricter and more demanding operation and control requirements, for utilizing their controllability and multi-function capability to the advantage of the power system. Examples of requirements for Low Voltage Ride Through (LVRT) capability and reactive power support are already well established in many countries as specified in the Grid Codes for connection of wind farms to the power system. It is also well known that other auxiliary functions like active filtering capability and resonance damping can be incorporated in the control of grid connected converters. Ability of temporarily operating limited parts of the power system as islanded Micro-Grid is also appearing as an advantageous option in the emerging SmartGrid context. Implementation of such additional functionalities can influence the design requirements of the converters and will lead to additional challenges for the control system. This is especially the case for high power converters designed with conventional high voltage Si-based semiconductors requiring low switching frequencies for achieving acceptable power conversion efficiency. By starting from conventional and emerging applications of grid connected power electronic converters, this presentation will identify and discuss the most critical challenges for design and control of converter units with multi-function capability. On this basis, it will be discussed how new semiconductor devices with lower losses and/or capability for higher switching frequencies can be utilized to improve the performance and alleviate the control challenges of grid connected power electronic converters.

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284 Information Schools in Asia-Pacific and their Collaboration

Faculty of Library, Information and Media Science, University of Tsukuba Research Center for Knowledge Communities, University of Tsukuba

285 Sep 30 (Tue) Meeting Room 5

Information Schools in Asia-Pacific and their Collaboration

Chair Shigeo Sugimoto University of Tsukuba

13:30-13:35 Shigeo Sugimoto University of Tsukuba Introduction

Development of Library and Information Science Major in China: Status 13:35-14:00 Li Guangjian Peking University and Trends

14:00-14:25 Kulthida Tuamsuk Khon Kaen University Information Schools in Thailand and Southeast Asia

14:25-14:50 Andrew B. Wertheimer University of Hawaii Studying Information as a Way to Promote Peace and Sustainability

Educating Information Professionals in the Department of Library 14:50-15:15 Emi Ishita Kyushu University Science at Kyushu University, Japan

15:15-15:25 Discussion

15:25-15:30 Shigeo Sugimoto University of Tsukuba Closing statement

286

20 / 26 ページ Sep 30 (Tue) Meeting Room 5

Information Schools in Asia-Pacific and their Collaboration

Chair Shigeo Sugimoto University of Tsukuba

13:30-13:35 Shigeo Sugimoto University of Tsukuba Introduction

Development of Library and Information Science Major in China: Status 13:35-14:00 Li Guangjian Peking University and Trends

14:00-14:25 Kulthida Tuamsuk Khon Kaen University Information Schools in Thailand and Southeast Asia

14:25-14:50 Andrew B. Wertheimer University of Hawaii Studying Information as a Way to Promote Peace and Sustainability

Educating Information Professionals in the Department of Library 14:50-15:15 Emi Ishita Kyushu University Science at Kyushu University, Japan

15:15-15:25 Discussion

15:25-15:30 Shigeo Sugimoto University of Tsukuba Closing statement

287

20 / 26 ページ Development of Library and Information Science Major in China: Status and Trends

Dr. Li Guangjian

Department of Information Management, Peking University E-mail: [email protected]

The history of library and information science education in China will be described. Spe- cial attention will be paid to the development of LIS major since late 1990s. Connection be- tween the major and society, especially the collaboration with other social institutions will also be discussed.

288 Information Schools in Thailand and Southeast Asia

Dr. Kulthida Tuamsuk

Faculty of Humanities and Social Sciences, Khon Kaen University E-mail: [email protected]

The report on situation of information education in Thailand and Southeast Asia at both undergraduate and post-graduate levels which covers: the policies at national and regional levels, the higher institutions which provide information education, the curricula and courses, the learning and teaching approaches, the international collaborations among them and with information schools in other regions, the information professions and its future.

289 Studying Information as a Way to Promote Peace and Sustainability

Dr. Andrew B. Wertheimer

Library & Information Science Program, Information & Computer Sciences Department, University of Hawaii E-mail: [email protected]

For several decades people have said that we are in the “Information Age,” but few disciplines have critically examined what this means, including the field of Library and Information Science (LIS). This presentation will build on Christine Pawley’s claim that LIS has been “Hegemony’s Handmaiden” ever since Melvil Dewey (1851-1931) established the field with help from Andrew Carnegie. After briefly critically reviewing these origins, the presentation will suggest we reconsider the vision of Belgian Paul Otlet (1868-1944) and his pre-internet Repertoire bibliographique universel (Universal Bibliographic Repertory), which also received Carnegie Funding. Otlet believed that organizing and providing global access to information worldwide would promote world peace. The presentation will also look at “Critical LIS” as a way of seeing how information can encourage peace and sustainability, by using counter-examples of those in power have grossly manipulated information given to voters, such as the disinformation which led to America’s Iraq War (2003-11). The presentation will conclude with a set of research agendas that could demonstrate the relevance of a Critical LIS in today’s complex information economy.

290 Educating Information Professionals in the Department of Library Science at Kyushu University, Japan

Dr. Emi Ishita

Department of Library Science, Graduate School of Integrated Frontier Sciences, Kyushu University E-mail: [email protected]

The Department of Library Science, Graduate School of Integrated Frontier Sciences, Kyushu University started the Master and Doctoral program in 2011 and 2013, respectively. Our department offers an integrated program base on Library and Information Science, Archival and Records Management Studies conducted by scholars with many different disciplines - Social Sciences, Humanities, and Computer and Information Sciences. Our department has strong relationship with the Kyushu University Library for education and training of students and for collaboration in the scholarly information community. This talk will overview the Department of Library Science at Kyushu University and briefly discuss its collaborative activities in the information schools’ community.

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292 Innovative Approaches to Natural Resources for Development of North African and Mediterranean Regions

Alliance for Research on North Africa (ARENA), University of Tsukuba

Tunis Office, University of Tsukuba

293 Sep 30 (Tue) Special Conference Room

Innovative Approaches to Natural Resources for Development of North African and Mediterranean Regions

Chair Kennichi Kashiwagi University of Tsukuba

Hiroko Isoda ARENA, University of Tsukuba Introduction

Application of Biotransformation as Lever of Development of Vegetable 13:40-14:20 Ismaili Alaoui Mustapha IAV Hassan II Biomasses

Research and Technology Energetic transition in Tunisia: 14:20-15:00 Brahim Bessaïs Centre of Energy BP. Tunisia Impacts on research activities and capacity buildings

15:00-15:20 Coffee Break

15:20-16:00 Majed Abu-Zreig German-Jordanian University Control of Agricultural Land Erosion in Jordan with Polyacrylamide

Mohammed Abdulla Al- 16:00-16:40 University of Bahrain, Bahrain. Oil and Gulf Economies within a Changing Regional Environment Sadiq

16:40 Mitsutoshi Nakajima ARENA, University of Tsukuba Closing statement

294

23 / 26 ページ Sep 30 (Tue) Special Conference Room

Innovative Approaches to Natural Resources for Development of North African and Mediterranean Regions

Chair Kennichi Kashiwagi University of Tsukuba

Hiroko Isoda ARENA, University of Tsukuba Introduction

Application of Biotransformation as Lever of Development of Vegetable 13:40-14:20 Ismaili Alaoui Mustapha IAV Hassan II Biomasses

Research and Technology Energetic transition in Tunisia: 14:20-15:00 Brahim Bessaïs Centre of Energy BP. Tunisia Impacts on research activities and capacity buildings

15:00-15:20 Coffee Break

15:20-16:00 Majed Abu-Zreig German-Jordanian University Control of Agricultural Land Erosion in Jordan with Polyacrylamide

Mohammed Abdulla Al- 16:00-16:40 University of Bahrain, Bahrain. Oil and Gulf Economies within a Changing Regional Environment Sadiq

16:40 Mitsutoshi Nakajima ARENA, University of Tsukuba Closing statement

295

23 / 26 ページ Application of Biotransformation as Lever of Development of Vegetable Biomasses

Ismaili Alaoui Mustapha

IAV Hassan II, BP 6202, Rabat Institute, Morocco

ungi I. Metabolism of R (+) pulègone. Tetrahedron Letters, Vol. 33, N°17, pp. 2349-2352. Morocco is a North African country that has a rich tradition in food technology. Many tra- ditional foods of animal or plant origin are still widely consumed and highly appreciated. Moroccan government is trying to promote the agriculture sector, in particular food industry using several programs and plans (Green Moroccan plan, Emergence plan, Human develop- ment programs, etc.). These programs aim to enhance productivity and quality through opti- mization of culture, technology and biotechnology. The major Food biotechnology program can be grouped around three main axis:

1- Control of traditional fermentations: A large part of process are still mainly located at the household level in poor sanitary conditions and marketed through informal channels. They remain beyond official control for compliance with national regulations and international standards. A large part of 120,000 tons of Moroccan table are exported after industrial fermentation process using selected endogenous strains from traditional fermentations. The objective is to valorize vegetables and animals products using microorganisms, spices, aromatic herbs and natural dehydration process. 2- Value-added products of sub-agro-industrial products by fermentation: Moroccan food industry produces more than 1 million tons of by-products (300 tons of olives cake, 300 tons of bagasse sugar, 200.000 tons of flour fish.etc.). A large part of these raw materials are scarcely exploited, and their elimination in nature is a threat to the environment. Proteins content of Olive cake were increased from 6 to 20 % using solid state fermentation with high digestibility. Some of selecting fungus was used to ferment olive cake to produce a large quantity of enzymes (lipases, esterase’s, phytase). Natural aromas, compounds used for cosmetic, food, and pharmaceutical industries were produced. The objective is to transform wastes into feeds or producing enzymes or aromas using solids state fermentation by fungus. 3- Valorization of natural materials by bioconversion using selecting strains of Fungus: The products of biological oxidation of some terpenoïds abundantly present in aromatic herbs (Eucalyptus, Mentha pulegium, Artemisia herba alba.etc) will be described with focus on the diverse region and stereoselectivities obtained from these terpenic compounds.

296 Energetic transition in Tunisia: Impacts on research activities and capacity buildings

Brahim Bessaïs and Amen-Allah Guizani

Research and Technology Centre of Energy BP. Tunisia

The energy balance of Tunisia reached a deficit beyond 2000. To overcome this deficit, Tunisia developed a strategy based on integrating renewable energy (RE) in the balance, aiming to constitute 30% of the total national energy production around 2030. Industrial integration development of RE and then creation of employment and value need capacities strengthening while focusing on research and development (R&D), innovation and technology Transfer. The ambitious energetic strategy of Tunisia needs the development of skills in RE technologies. RE may efficiently contribute to sustainable development (creation of jobs and development of inland regions) targeting to reduce the regional instability and the impact of fossil fuels. In this context, as a government institution the Research and Technology Centre of Energy (CRTEn) has among other responsibilities capacity building, and technology survey and transfer mainly in Solar thermal and Solar PV. Solar thermal activities address low and mid temperature starting with interest to the material, the component and the complete systems, aiming to master technologies that support local industries. The main solar applications targeted are production of Domestic Hot Water, agricultural greenhouses, cooling, drying and desalination. Efforts are focused the last three years on CSP (Concentrated Solar Power), which could have an important impact as some power plants are planned using this concept in the near future, in an effort to enhance the Renewable Energy share in the energy mix. Tunisia (CRTEn) was the first Arab and African country who produces silicon solar cells at a pilot level in 1990 with a yield of about 11%. Technological progress led in 1993 to an average efficiency of 12-13%. Thanks to nanosciences, the CRTEn succeeded to introduce silicon nanostructures as: • Antireflective and passivation coatings in Si solar cells. • Precursors for achieving cheap grooves using inexpensive chemical techniques. • Precursors to purify the base material, and improve the electrical and optoelectronic properties of Si solar cells.

297 Control of Agricultural Land Erosion in Jordan with Polyacrylamide

Majed Abu-Zreig

Department of Water and Environmental Engineering, German-Jordanian University, Jordan

Land erosion is considered one of the most detrimental processes to the productivity and degradation of agricultural lands. The damaging effect is even more profound in arid and semi arid climates where lands are subjected to sever droughts and scarce rainfall conditions such as in Jordan. The use of polyacryamide for soil conservation is being considered by the authors under filed and natural rainfall conditions. Two types of polyacrylamide were used to test their influence on soil erosion and runoff of sloping land in Jordan under natural rainfall conditions. The two PAM used in this study, commercially named as A836 and A870, have different molecular weight ranging qualitatively from high to low and surface charge from 20% to 70%, respectively. Fourteen field plots with 2 m wide by 10 m long having a slope of 11% were constructed in the field. A runoff collection barrels were installed at the end of plots to monitor the amount of runoff and sediment loss after each storm. The PAMs were applied at 2 application rates of 10 and 30 kg/ha plus a control. Experimental results showed that Both types of PAM caused large reduction in soil loss with an average value of 22% compared to control and 70% compared to compacted plots. Application of A836 reduced runoff and sediment loss by 23% and 35%, respectively compared to control. The corresponding average decreases in runoff and soil loss for A870 were lower at 16% and 8%, respectively. Differences in runoff among PAM treated plots at 10 and 30 kg/ha were negligible but soil loss was slightly lower in the 30 kg/ha PAM treated plots.

Key Words: PAM, Field plots, Soil loss, Moisture conservation

298 Oil and Gulf Economies within a Changing Regional Environment

Mohammed Abdulla Al-Sadiq

Dept. of Finance and Business Studies Unit, Deanship of Scientific Research - University of Bahrain, Bahrain

For more than 50 years, the oil sector has had an important impact on the overall economies of Gulf Cooperation Council (GCC) countries. It is worth mentioning that Bahrain was the first country in the Arabian Gulf region in which oil was discovered in 1932. But it was not until the quadrupling of oil prices during the period October 1973 to January 1974, as a result of the coordinated action by OPEC members to raise the price of oil, that substantial amounts of financial capital became available and provided the potential for rapid economic development. Since the mid-seventies, the role of the GCC countries in the international oil market (IOM) has been increasingly important. It has played an important role, through OPEC, in directing the oil sector in the world.

Oil revenues have transformed most of the aspects of socio-economic life in the GCC countries. They have contributed to the establishment of the infrastructure, support in founding industrial companies, and for the financing of education, culture, defense and security.

The banking offshore industry expanded rapidly, and since 1980, Bahrain has become an important financial centre in the region.

The acceleration of investment spending and the continuous growth of various economic sectors led to a rapid inflow of foreign labour which recently accounts for more than half of the total labour force in GCC economies.

The 2003-2008 oil price boom spurred economic activity in the area and strengthened the performance of all economic sectors. Since 2004 at the latest, many GCC countries have joined the ranks of the fastest growing economies in the world. Tremendous prosperity has been witnessed in the cities like Riyadh, Kuwait, Manama, Doha, Abu-Dhabi, Dubai, and Muscat

This paper attempts to look at the impact of oil on the GCC economies with special empha- sis on its development, security and future prospects.

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300 G30 Joint Seminar Borderless Challenge Towards Global Aging by Young Power: Comparative Analysis of Long Term Care in the World

Faculty of Humanities and Social Sciences Faculty of Medicine University of Tsukuba

301 Sep 30 (Tue) Annex Hall

G30 Joint Seminar Borderless Challenge Towards Global Aging by Young Power: Comparative Analysis of Long Term Care in the World

Chair Miyoko Motozawa University of Tsukuba Chair Nanako Tamiya University of Tsukuba

Gerhard Igl University of Kiel

13:00-13:40 Introduction

Nanako Tamiya University of Tsukuba

13:40-13:55 Jason Thompson University of Tsukuba Aging and long term care in U.S.A

13:55-14:10 Issei Watanabe University of Tsukuba Aging and long term care in Japan

14:10-14:25 DaEun Ariana Han University of Tsukuba Aging and long term care in South Korea

14:25-14:40 Eric Adjepong Kwarteng University of Tsukuba Aging and long term care in Ghana

14:40-14:55 Drauna Adi Miriama University of Tsukuba Aging and long term care in Fiji

14:55-15:10 Josephine Laker University of Tsukuba Aging and long term care in South Africa

15:10-15:25 Comments

Gerhard Igl University of Kiel

15:25-15:45 Closing statement

Nanako Tamiya University of Tsukuba

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G30 Joint Seminar Borderless Challenge Towards Global Aging by Young Power: Comparative Analysis of Long Term Care in the World

Chair Miyoko Motozawa University of Tsukuba Chair Nanako Tamiya University of Tsukuba

Gerhard Igl University of Kiel

13:00-13:40 Introduction

Nanako Tamiya University of Tsukuba

13:40-13:55 Jason Thompson University of Tsukuba Aging and long term care in U.S.A

13:55-14:10 Issei Watanabe University of Tsukuba Aging and long term care in Japan

14:10-14:25 DaEun Ariana Han University of Tsukuba Aging and long term care in South Korea

14:25-14:40 Eric Adjepong Kwarteng University of Tsukuba Aging and long term care in Ghana

14:40-14:55 Drauna Adi Miriama University of Tsukuba Aging and long term care in Fiji

14:55-15:10 Josephine Laker University of Tsukuba Aging and long term care in South Africa

15:10-15:25 Comments

Gerhard Igl University of Kiel

15:25-15:45 Closing statement

Nanako Tamiya University of Tsukuba

303

24 / 26 ページ G30 Joint Seminar Borderless Challenge Towards Global Aging by Young Power: Comparative Analysis of Long Term Care in the World

Prof. Miyoko Motozawa and Prof. Nanako Tamiya

The world is aging rapidly and will continue to age at a great speed. A report by UFPA predicts that by 2050, senior person aged 60 years and over will make up more than 80 percent of the population in developing countries. Developed countries have been experiencing this ageing phenomenon from an earlier point in time and have been pushed to adapt their systems accordingly at a great expense of resources. This unprecedented phenomenon in human history will also force emerging economies to adapt themselves to face the upcoming challenges. However, social and economic disparities among developing and emerging economies pose an even harder and complex scenario. These countries are eagerly looking at what more advanced aged countries are doing to tackle the problems arisen from an increasing greyer population. Many countries around the world, developed and developing ones have a great interest in what the fruits of long term care system in Japan and Germany. However, it might be very important to discuss whether these countries need to adapt the system or not. It is under these circumstances that we, at the university of Tsukuba, G30 joint seminar (Faculty of Humanities and Social Sciences and Faculty of Medicine), to create a meeting point of discussion where students and faculty from all over the world have been invited to participate and share their experiences around the aging of our societies, and by doing this being able to acquire a global perspective of a problems that affects us all. Our section aims at understanding and comparing the situation of the ageing process in each participant country from a varied set of viewpoints, and building a road to a long-term care policy adapted to each particular setting base on joint seminar held on September 24 and 25, 2014.

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306 Symposium for International Collaboration of Science & Technology, and Innovative Development in Central and East Asia

Center for Innovative Development of Science and New Technologies of Academy of Sciences of the Republic of Tajikistan Department of International Exchange & Cooperation, Dalian Nationalities University, China Faculty of Life and Environmental Sciences, University of Tsukuba

307 Sep 30 (Tue) Meeting Room 3

Symposium for International Collaboration of Science & Technology, and Innovative Development in Central and East Asia

(1) International Collaboration of Science & Technology, and Innovative Development in Central and East Asia: PART1 Chair Kenji Tamura University of Tsukuba Science Academy of the 13:30-14:30 Mamadsho Ilolov Republic of Tajikistan Innovative development of the Republic of Tajikistan

14:30-15:10 Ubaidulloev Zubaidullo University of Tsukuba

15:10-15:30 Discussion

15:30-15:50 Coffee Break (2) International Collaboration of Science & Technology, and Innovative Development in Central and East Asia: PART2 Chair Kenji Tamura University of Tsukuba 15:50-16:20 Xiaohui Wang Dalian Nationalities University International Exchange and Cooperation of Science & Technology, Sports, & Arts- between China and Japan

16:20-16:50 Wuyunna Dalian Nationalities University International Collaboration for Conservation of Asian Steppe Grassland

16:50-17:20

17:20-17:50 Discussion

308

26 / 26 ページ Sep 30 (Tue) Meeting Room 3

Symposium for International Collaboration of Science & Technology, and Innovative Development in Central and East Asia

(1) International Collaboration of Science & Technology, and Innovative Development in Central and East Asia: PART1 Chair Kenji Tamura University of Tsukuba Science Academy of the 13:30-14:30 Mamadsho Ilolov Republic of Tajikistan Innovative development of the Republic of Tajikistan

14:30-15:10 Ubaidulloev Zubaidullo University of Tsukuba

15:10-15:30 Discussion

15:30-15:50 Coffee Break (2) International Collaboration of Science & Technology, and Innovative Development in Central and East Asia: PART2 Chair Kenji Tamura University of Tsukuba 15:50-16:20 Xiaohui Wang Dalian Nationalities University International Exchange and Cooperation of Science & Technology, Sports, & Arts- between China and Japan

16:20-16:50 Wuyunna Dalian Nationalities University International Collaboration for Conservation of Asian Steppe Grassland

16:50-17:20

17:20-17:50 Discussion

309

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