Grant-in-Aid for Scientific Research(S) Integrated Disciplines … · 2018-12-10 · Markov Bases in Algebraic Statistics. Springer Series in Statistics, Vol. 199. Springer. 2012

【Grant-in-Aid for Scientific Research(S)】 Integrated Disciplines (Informatics)

Title of Project： Innovation in statistics and related mathematics through computational algebraic statistics

Akimichi Takemura ( The University of Tokyo, Graduate School of Information Science and Technology, Professor )

Research Area： Informatics Keyword： Statistical inference, Computational algebraic statistics

【Purpose and Background of the Research】 The purpose of this project is to bring new

innovation to statistics and related fields of mathematics, such as the commutative algebra and the D-module theory, through further developments in computational algebraic statistics. Takemura, Hibi and Takayama, have been very

successfully collaborating on problems of computational algebraic statistics and younger researchers have been joining our collaboration. Close collaboration among statisticians and algebraists of our group is unique even in the world and we aim to make major contribution to the development of computational algebraic statistics on the international level.

【Research Methods】 Takemura, Hibi and Takayama will collaborate on

computational algebraic statistics from the background of their own special fields. This collaboration will lead to developments relevant to both statistics and mathematics. More concretely, we further develop toric ideals associated with discrete exponential family of distributions and the holonomic gradient method proposed by us recently. Takemura will pose problems relevant to statistical applications. Hibi will solve them based on his expertise on toric ideals and Takayama will solve them based on his expertise on the ring of differential operators. Takayama will implement the solutions in algebraic computational software. For developments of holonomic gradient method,

we need machinery from various fields, such as the distribution theory of statistics and Gröbner basis for ring of differential operators. This will contribute to innovation in both statistics and related fields of mathematics.

【Expected Research Achievements and Scientific Significance】 Since the breakthrough paper by Diaconis and

Sturmfels in 1998, which established the equivalence of toric ideals and Markov bases, the field of computational algebraic statistics developed

rapidly and brought relevant results both to statistics and algebra. New important results on Markov bases are still being found and we will contribute further to this area. The holonomic gradient method was recently

proposed in the collaboration of Takemura, Hibi and Takayama. The usefulness of this method is based on the fact that the common probability distributions used in statistics are holonomic functions of both the observation and the parameter. From the general theory of holonomic functions, the normalizing constants and the probability of regions are holonomic in the parameter. Hence these quantities and the maximum likelihood estimation can be evaluated by solving partial differential equations instead of numerical integrations. This will bring reformulation of the whole distribution theory in statistics.

【Publications Relevant to the Project】・Satoshi Aoki, Hisayuki Hara and Akimichi

Takemura. Markov Bases in Algebraic Statistics. Springer Series in Statistics, Vol. 199. Springer. 2012.

・Holonomic gradient method for the distribution function of the largest root of a Wishart matrix. Journal of Multivariate Analysis, 117, 296-312. Hiroki Hashiguchi, Yasuhide Numata, Nobuki Takayama and Akimichi Takemura. 2013.

・Graver basis for an undirected graph and its application to testing the beta model of random graphs. Annals of the Institute of Statistical Mathematics, 65, 191-212. Mitsunori Ogawa, Hisayuki Hara and Akimichi Takemura. 2013.

【Term of Project】FY2013-2017

【Budget Allocation】108,600 Thousand Yen

【Homepage Address and Other Contact

Information】 http://park.itc.u-tokyo.ac.jp/atstat/kakenhi/h25s/ [email protected]


Title of Project： A Study on Building-Block Computing Systems using Inductive Coupling Interconnect

Hideharu Amano ( Keio University, Faculty of Science and Technology, Professor )

Research Area： Informatics Keyword： Computer Architecture

【Purpose and Background of the Research】 Building-Block Computing systems enable to build

an appropriate system for the target application just by selecting required chips: CPU, memory modules and accelerators and stacking them. Inductive coupling interconnect between chips form a network –on-chip automatically, and a system is optimized even if the specification is not fixed beforehand. For realizing such systems, inter-chip wireless inductive coupling techniques, self-organized network-on-chips, fault tolerant architectures, optimized power control, and a flexible operating system with virtualization facilities are investigated.

【Research Methods】 For establishment of building-block computing

systems, crosscutting researches on circuit, architectures and system software are required. The followings will be investigated in each research field: (1) Although a number of research trials have been reported, the standard design flow of inductive coupling has not been established. Our first goal is developing an IP (Intellectual Property) of inductive coupling interconnect for easy use of the technology. In order to reduce the footprint of inductors, digital circuits must be implemented inside the inductors. Power supply using inductive coupling link is also our challenge. (2) Self-organized network-on-chip which can be formed just by stacking chips will be investigated. (3) Techniques on fault tolerant self optimizing architectures are important to form building-block systems. (4) Power control is essential in 3D chip stacking, since the heat dissipation is difficult. We will use integrated power control techniques from the system software to circuits. (5) A flexible operating system with virtualization technique is needed to integrate all chips into a system. We will develop the first prototype multi-core

system using inductive coupling in 2013. Based on the prototype, techniques on each layer will be investigated. In 2016, we will develop a final system in which various chips can be stacked as shown in Figure 1, and demonstrate our techniques on it.

Figure 1 The final prototype

【Expected Research Achievements and

Scientific Significance】 Building block computing systems can solve

problems on recent advanced semiconductor technologies: I/O problems and expanding cost to develop a large chip. It can be applied wide area of embedded systems including censor networks for cyber physical space and car electronics. The lifetime of the product will be stretched by replacing chips. It also contributes the reuse of the chips and so save the earth resource.

【Publications Relevant to the Project】・3-D NoC Inductive Coupling Links for

Building Block SoCs,” Yasuhiro Take, Hiroki Matsutani, Daisuke Sasaki, Michihiro Koibuchi, Tadahiro Kuroda, Hideharu Amano, IEEE Trans. on Computers,(In press)

・N. Miura, T. Shidei, Y. Yuan, S. Kawai, K. Takatsu, Y. Kiyota, Y. Asano, and T. Kuroda, “A 0.55V 10fJ/bit Inductive-Coupling Data Link and 0.7V 135fJ/Cycle Clock Link with Dual-Coil Transmission Scheme,”IEEE JSSC, vol.46, no.4, pp.965-973, Apr. 2011

【Term of Project】FY2013-2017 【Budget Allocation】166,400 Thousand Yen 【Homepage Address and Other Contact

Information】http://www.am.ics.keio.ac.jp/kaken_s

Integrated Disciplines (Informatics)

－64－


Title of Project： Innovation in statistics and related mathematics through computational algebraic statistics

Akimichi Takemura ( The University of Tokyo, Graduate School of Information Science and Technology, Professor )

Research Area： Informatics Keyword： Statistical inference, Computational algebraic statistics

【Purpose and Background of the Research】 The purpose of this project is to bring new

innovation to statistics and related fields of mathematics, such as the commutative algebra and the D-module theory, through further developments in computational algebraic statistics. Takemura, Hibi and Takayama, have been very

successfully collaborating on problems of computational algebraic statistics and younger researchers have been joining our collaboration. Close collaboration among statisticians and algebraists of our group is unique even in the world and we aim to make major contribution to the development of computational algebraic statistics on the international level.

【Research Methods】 Takemura, Hibi and Takayama will collaborate on

computational algebraic statistics from the background of their own special fields. This collaboration will lead to developments relevant to both statistics and mathematics. More concretely, we further develop toric ideals associated with discrete exponential family of distributions and the holonomic gradient method proposed by us recently. Takemura will pose problems relevant to statistical applications. Hibi will solve them based on his expertise on toric ideals and Takayama will solve them based on his expertise on the ring of differential operators. Takayama will implement the solutions in algebraic computational software. For developments of holonomic gradient method,

we need machinery from various fields, such as the distribution theory of statistics and Gröbner basis for ring of differential operators. This will contribute to innovation in both statistics and related fields of mathematics.

【Expected Research Achievements and Scientific Significance】 Since the breakthrough paper by Diaconis and

Sturmfels in 1998, which established the equivalence of toric ideals and Markov bases, the field of computational algebraic statistics developed

rapidly and brought relevant results both to statistics and algebra. New important results on Markov bases are still being found and we will contribute further to this area. The holonomic gradient method was recently

proposed in the collaboration of Takemura, Hibi and Takayama. The usefulness of this method is based on the fact that the common probability distributions used in statistics are holonomic functions of both the observation and the parameter. From the general theory of holonomic functions, the normalizing constants and the probability of regions are holonomic in the parameter. Hence these quantities and the maximum likelihood estimation can be evaluated by solving partial differential equations instead of numerical integrations. This will bring reformulation of the whole distribution theory in statistics.

【Publications Relevant to the Project】・Satoshi Aoki, Hisayuki Hara and Akimichi

Takemura. Markov Bases in Algebraic Statistics. Springer Series in Statistics, Vol. 199. Springer. 2012.

・Holonomic gradient method for the distribution function of the largest root of a Wishart matrix. Journal of Multivariate Analysis, 117, 296-312. Hiroki Hashiguchi, Yasuhide Numata, Nobuki Takayama and Akimichi Takemura. 2013.

・Graver basis for an undirected graph and its application to testing the beta model of random graphs. Annals of the Institute of Statistical Mathematics, 65, 191-212. Mitsunori Ogawa, Hisayuki Hara and Akimichi Takemura. 2013.




Information】 http://park.itc.u-tokyo.ac.jp/atstat/kakenhi/h25s/ [email protected]


Title of Project： A Study on Building-Block Computing Systems using Inductive Coupling Interconnect

Hideharu Amano ( Keio University, Faculty of Science and Technology, Professor )

Research Area： Informatics Keyword： Computer Architecture

【Purpose and Background of the Research】 Building-Block Computing systems enable to build

an appropriate system for the target application just by selecting required chips: CPU, memory modules and accelerators and stacking them. Inductive coupling interconnect between chips form a network –on-chip automatically, and a system is optimized even if the specification is not fixed beforehand. For realizing such systems, inter-chip wireless inductive coupling techniques, self-organized network-on-chips, fault tolerant architectures, optimized power control, and a flexible operating system with virtualization facilities are investigated.

【Research Methods】 For establishment of building-block computing

systems, crosscutting researches on circuit, architectures and system software are required. The followings will be investigated in each research field: (1) Although a number of research trials have been reported, the standard design flow of inductive coupling has not been established. Our first goal is developing an IP (Intellectual Property) of inductive coupling interconnect for easy use of the technology. In order to reduce the footprint of inductors, digital circuits must be implemented inside the inductors. Power supply using inductive coupling link is also our challenge. (2) Self-organized network-on-chip which can be formed just by stacking chips will be investigated. (3) Techniques on fault tolerant self optimizing architectures are important to form building-block systems. (4) Power control is essential in 3D chip stacking, since the heat dissipation is difficult. We will use integrated power control techniques from the system software to circuits. (5) A flexible operating system with virtualization technique is needed to integrate all chips into a system. We will develop the first prototype multi-core

system using inductive coupling in 2013. Based on the prototype, techniques on each layer will be investigated. In 2016, we will develop a final system in which various chips can be stacked as shown in Figure 1, and demonstrate our techniques on it.

Figure 1 The final prototype


Scientific Significance】 Building block computing systems can solve

problems on recent advanced semiconductor technologies: I/O problems and expanding cost to develop a large chip. It can be applied wide area of embedded systems including censor networks for cyber physical space and car electronics. The lifetime of the product will be stretched by replacing chips. It also contributes the reuse of the chips and so save the earth resource.

【Publications Relevant to the Project】・3-D NoC Inductive Coupling Links for

Building Block SoCs,” Yasuhiro Take, Hiroki Matsutani, Daisuke Sasaki, Michihiro Koibuchi, Tadahiro Kuroda, Hideharu Amano, IEEE Trans. on Computers,(In press)

・N. Miura, T. Shidei, Y. Yuan, S. Kawai, K. Takatsu, Y. Kiyota, Y. Asano, and T. Kuroda, “A 0.55V 10fJ/bit Inductive-Coupling Data Link and 0.7V 135fJ/Cycle Clock Link with Dual-Coil Transmission Scheme,”IEEE JSSC, vol.46, no.4, pp.965-973, Apr. 2011


Information】http://www.am.ics.keio.ac.jp/kaken_s

－65－

Grant-in-Aid for Scientific

Research (S)

【Grant-in-Aid for Scientific Research (S) 】 Integrated Disciplines (Informatics)

Title of Project： Collecting, Analyzing, and Evaluating Software Assets for Effective Reuse

Katsuro Inoue ( Osaka University, Graduate School of Information Science and Technology, Professor )

Research Area： Software Keyword： Software Engineering

【Purpose and Background of the Research】 Recent software development employs various

kinds of software assets including Open Source Software OSS and proprietary systems. Efficient and effective reuse of assets is extremely important to the success of software development project. In this project, we will propose a support framework, named SARF (Software Asset Reuse Framework), for effective reuse of software assets. Figure 1 shows an overview of SARF. At Step 1, it collects and analyzes various kinds of software assets in the Internet or in the organizations. At Step 2, the collected assets are evaluated quantitatively to get their values. At Step 3, the values and other associated data on the assets are visualized for efficient development support using integrated development environment IDE. Using various background techniques on code

search, clone analysis, metrics, program analysis and reuse, we will explore the approaches to each step, and will develop prototype systems. Furthermore, based on the evaluation of the prototypes, practical systems will be implemented and released as OSS to get many users. 【Research Methods】 We will develop various novel approaches and methods for each step. For Step 1, we will design a project search engine which efficiently finds similar and related projects to a project (see Figure 2). A meta-search approach with external code search engines would be used for this purpose. Step 2 will be composed of two value models with the global

Figure 1 Overview of SARF

SourceForge GitHub

Apache

Colle

ctio

n of P

roje

cts

Searc

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ey

Extra

ctio

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Assets in the Internet

Internal Assets

Asset Repository

ProjectSearch Engine

GoogleCode

Koders

Figure 2 Overview of Project Search Engine

and empirical ones. The former is similar to Page Rank model using software project relations. Step 3 would use city metaphor visualization for various values and associated date of the assets. Also, an IDE composed of the above mentioned systems will be developed.

【Expected Research Achievements and Scientific Significance】 Novel approaches for each step will be important

contributions to software engineering research community. The developed systems will be widely distributed to boost the software asset reuse.

【Publications Relevant to the Project】・Katsuro Inoue, et al., Where Does This Code

Come from and Where Does It Go? -Integrated Code History Tracker for Open Source Systems-, 34-ICSE, pp.331-341, Zurich, Switzerland, 2012.

・Pei Xia, et al., Studying Reuse of Out-dated Third-party Code in Open Source Projects, Japan Society for Software Science and Technology (accepted).


【Budget Allocation】93, 500 Thousand Yen


Information】 http://sel.ist.osaka-u.ac.jp/SARF/index.html. [email protected]


SourceForge GitHub

Apache

Proprietary Assets Asset Repository(Software+Analysis Data)

Developer

Various Assets

New System

Efficient Development

① ② ③

Collect/A

nalysis

Quantitative

Evaluation

Reuse S

upport

InsideOrganization

Support Systems for Asset ReuseOutside Organization


Title of Project： Studies on semi-autonomous teleoperated androids that have humanlike presence

Hiroshi Ishiguro ( Osaka University, Graduate School of Engineering Science,

Professor )

Research Area： Informatics Keyword： Intelligent robot

【Purpose and Background of the Research】 The principle investigator has developed the first

teleoperated android in the world as the ultimate teleoperated interactive robot. The android that has the very humanlike appearance is the ideal interactive robot since human brain has innate functions to recognize humans. We can obtain knowledge of human cognition through cognitive experiments with the androids and improve the androids’ functions by using the obtained knowledge. One of the important issues in the development of the androids is the actuator. DC servo motors and pneumatic actuators are used for the robots and androids so far. However, these actuators cannot reproduce all the properties of human muscle. The principle investigator and his colleagues have recently developed powerful electromagnetic linear actuators that are suitable for humanoids and androids. The actuator can reproduce spring property of human muscle and enables us to develop an android that can safely contact with people. Against the technical background, this research project aims to realize semi-autonomous teleoperated androids as research platforms for research and development of teleoperated robots by extending both of the software and hardware functions (See the below figure).

【Research Methods】 This research project improve teleoperation

functions of the teleoperated android and realizes more realistic and expressive interactions through multiple modalities, such as vision, audition and tactile sensation, beyond abilities of teleoperation of operators. This is an ambitious challenge to answer

to the following questions. Can we represent human presence with machine? Can we accept the androids as humans in our society? The first step is to develop an interactive android that can have humanlike interactions with people by using the electromagnetic linear actuators that can reproduce properties of human muscle. That is, we will develop androids that have not only humanlike appearance but also humanlike tactile interaction. And then, we will replace teleoperated functions in the previous androids with autonomous functions.

【Expected Research Achievements and Scientific Significance】 The principle investigator has started the android

project in 2006. After that, the project is drawing people’s attention and it has been well-known in the world. This research project develops more advanced social functions of the teleoperated android based on results of the previous studies and establish design policies for autonomous systems that are used in our future society. In addition, it spawns new research areas of human sociality and the applications by giving systematic viewing points to cognitive studies on human sociality.

【Publications Relevant to the Project】・H. Ishiguro, How can we create “human”? I have

been an android, Shinchosya, 2011. ・H. Ishiguro, Possibilities of the total Turing test

with androids, Transaction of the Japanese Society for Artificial Intelligence, Vol. 26, No. 1, pp. 50-54, 2011.




Information】 http://www.irl.sys.es.osaka-u.ac.jp/ http://www.geminoid.jp/ja/index.html

－66－

【Grant-in-Aid for Scientific Research (S) 】 Integrated Disciplines (Informatics)

Title of Project： Collecting, Analyzing, and Evaluating Software Assets for Effective Reuse

Katsuro Inoue ( Osaka University, Graduate School of Information Science and Technology, Professor )

Research Area： Software Keyword： Software Engineering

【Purpose and Background of the Research】 Recent software development employs various

kinds of software assets including Open Source Software OSS and proprietary systems. Efficient and effective reuse of assets is extremely important to the success of software development project. In this project, we will propose a support framework, named SARF (Software Asset Reuse Framework), for effective reuse of software assets. Figure 1 shows an overview of SARF. At Step 1, it collects and analyzes various kinds of software assets in the Internet or in the organizations. At Step 2, the collected assets are evaluated quantitatively to get their values. At Step 3, the values and other associated data on the assets are visualized for efficient development support using integrated development environment IDE. Using various background techniques on code

search, clone analysis, metrics, program analysis and reuse, we will explore the approaches to each step, and will develop prototype systems. Furthermore, based on the evaluation of the prototypes, practical systems will be implemented and released as OSS to get many users. 【Research Methods】 We will develop various novel approaches and methods for each step. For Step 1, we will design a project search engine which efficiently finds similar and related projects to a project (see Figure 2). A meta-search approach with external code search engines would be used for this purpose. Step 2 will be composed of two value models with the global

Figure 1 Overview of SARF

SourceForge GitHub

Apache

Colle

ctio

n of P

roje

cts

Searc

h K

ey

Extra

ctio

n


Internal Assets

Asset Repository

ProjectSearch Engine

GoogleCode

Koders

Figure 2 Overview of Project Search Engine

and empirical ones. The former is similar to Page Rank model using software project relations. Step 3 would use city metaphor visualization for various values and associated date of the assets. Also, an IDE composed of the above mentioned systems will be developed.

【Expected Research Achievements and Scientific Significance】 Novel approaches for each step will be important

contributions to software engineering research community. The developed systems will be widely distributed to boost the software asset reuse.

【Publications Relevant to the Project】・Katsuro Inoue, et al., Where Does This Code

Come from and Where Does It Go? -Integrated Code History Tracker for Open Source Systems-, 34-ICSE, pp.331-341, Zurich, Switzerland, 2012.

・Pei Xia, et al., Studying Reuse of Out-dated Third-party Code in Open Source Projects, Japan Society for Software Science and Technology (accepted).




Information】 http://sel.ist.osaka-u.ac.jp/SARF/index.html. [email protected]


SourceForge GitHub

Apache

Proprietary Assets Asset Repository(Software+Analysis Data)

Developer

Various Assets

New System

Efficient Development

① ② ③

Collect/A

nalysis

Quantitative

Evaluation

Reuse S

upport

InsideOrganization

Support Systems for Asset ReuseOutside Organization


Title of Project： Studies on semi-autonomous teleoperated androids that have humanlike presence

Hiroshi Ishiguro ( Osaka University, Graduate School of Engineering Science,

Professor )

Research Area： Informatics Keyword： Intelligent robot

【Purpose and Background of the Research】 The principle investigator has developed the first

teleoperated android in the world as the ultimate teleoperated interactive robot. The android that has the very humanlike appearance is the ideal interactive robot since human brain has innate functions to recognize humans. We can obtain knowledge of human cognition through cognitive experiments with the androids and improve the androids’ functions by using the obtained knowledge. One of the important issues in the development of the androids is the actuator. DC servo motors and pneumatic actuators are used for the robots and androids so far. However, these actuators cannot reproduce all the properties of human muscle. The principle investigator and his colleagues have recently developed powerful electromagnetic linear actuators that are suitable for humanoids and androids. The actuator can reproduce spring property of human muscle and enables us to develop an android that can safely contact with people. Against the technical background, this research project aims to realize semi-autonomous teleoperated androids as research platforms for research and development of teleoperated robots by extending both of the software and hardware functions (See the below figure).

【Research Methods】 This research project improve teleoperation

functions of the teleoperated android and realizes more realistic and expressive interactions through multiple modalities, such as vision, audition and tactile sensation, beyond abilities of teleoperation of operators. This is an ambitious challenge to answer

to the following questions. Can we represent human presence with machine? Can we accept the androids as humans in our society? The first step is to develop an interactive android that can have humanlike interactions with people by using the electromagnetic linear actuators that can reproduce properties of human muscle. That is, we will develop androids that have not only humanlike appearance but also humanlike tactile interaction. And then, we will replace teleoperated functions in the previous androids with autonomous functions.

【Expected Research Achievements and Scientific Significance】 The principle investigator has started the android

project in 2006. After that, the project is drawing people’s attention and it has been well-known in the world. This research project develops more advanced social functions of the teleoperated android based on results of the previous studies and establish design policies for autonomous systems that are used in our future society. In addition, it spawns new research areas of human sociality and the applications by giving systematic viewing points to cognitive studies on human sociality.

【Publications Relevant to the Project】・H. Ishiguro, How can we create “human”? I have

been an android, Shinchosya, 2011. ・H. Ishiguro, Possibilities of the total Turing test

with androids, Transaction of the Japanese Society for Artificial Intelligence, Vol. 26, No. 1, pp. 50-54, 2011.




Information】 http://www.irl.sys.es.osaka-u.ac.jp/ http://www.geminoid.jp/ja/index.html

－67－


Research (S)


Title of Project： Research on Active Coordination Technology for Human Symbiotic Robot

Shigeki Sugano ( Waseda University, Faculty of Science and Engineering, Professor )

Research Area： Human informatics, Intelligent roboticsKeyword： Intelligent robot, Intelligent information processing

【Purpose and Background of the Research】 Labor shortages caused by aging society have

become a severe problem in developed countries. Because symbiotic robots can work with humans or support them in daily life, public and medical and welfare services, interest in human symbiotic robots has increased in these countries. These robots are expected to share a place at the same time with humans. Safety and work-efficiency are key issues for these robots. In the conventional framework of human symbiotic robots, it has been thought for long time that robots must avoid physical interactions with humans to ensure safety.

We consider this concept a major hurdle to enable robots to work efficiently with humans. Thus, we propose a shift of paradigm from: robots must avoid physical interactions with humans, to robots should actively coordinate with humans. We believe this paradigm shift can be a breakthrough to develop human symbiotic robots that are both safe and efficient. The purpose of this study is to establish a methodology to design mechanical structures and intelligent human symbiotic robots that coordinate actively with humans (Fig. 1).

【Research Methods】

This study can be divided into two major subjects. One is modeling the interaction between humans and robots both from a psychological and physiological (statics and dynamics) viewpoint. The second is to develop novel control theory and intelligence based on these models. We will validate experimentally these models using robots such as upper body humanoids with flexible manipulators and bipedal humanoid robot (Fig. 2). These investigations will be conducted in three major situations where interaction between humans and

robots occurs: (A) Weak contacts to teach one's direction. (B) Dynamic contacts for coordination (C) Actions to make a human to move


Scientific Significance】 There are a few studies on physical interactions

between humans and robots, especially active coordination between them. This study aims to establish a general methodology that can be used in various situations, whereas conventional studies in this field focus on a specific situation.

Once the methodology is established, it can be used in the design of various kinds of human symbiotic robots such as humanoid robots, human assisting devices, rehabilitation equipment and personal mobility systems.

【Publications Relevant to the Project】 H. Iwata and S. Sugano, “Design of human

symbiotic robot TWENDY-ONE,” in Proc. IEEE Int. Conf. Robotics and Automation (ICRA), pp. 580-586, 2009. Yo Kobayashi, Masakatsu G. Fujie, et al. , “Soft

interaction between body weight support system and human using fractional impedance Control”, Advanced Robotics, 26, pp. 1253-1269, 2012.




Information】http://www.sugano.mech.waseda.ac.jp/ http://www.twendyone.com/ http://www.takanishi.mech.waseda.ac.jp/ http://www.fujie.mech.waseda.ac.jp/

Figure 2 Research method

contact Modeling

Reconstruction

Figure 1 Research purpose

【Grant-in-Aid for Scientific Research(S)】 Integrated Disciplines (Environmental science)

Title of Project： Five-dimensional data assimilation of aerosol based on integrated analysis of multi-wavelength lidar and chemical transport model

Itsushi Uno ( Kyushu University, Research Institute for Applied Mechanics, Professor )

Research Area： Environmental dynamic analysis, Environmental science Keyword： Lidar, aerosol, chemical transport model, data assimilation

【Purpose and Background of the Research】 Asia is one of the biggest emission sources of

atmospheric pollutants in the world. Besides anthropogenic emissions, this region is also a major source of pollutants from biomass burning. Sulfates and black carbon particles in the air control and accelerate global warming, respectively. Aerosols exists in the atmosphere for 1 – 2 weeks and shows large temporal and spatial variation. Because the potential of aerosols to contribute to global warming depends on their composition, particle diameter and vertical profiles, it is necessary to integrate field measurements with chemical transport models which contain detailed aerosol information.

【Research Methods】 We will observe atmospheric aerosols from the

main air pollutant sources in Asia using a newly developed multi-wavelength Lidar system located in three sites in Japan. This new Lidar system is designed to retrieve the composition of aerosols including black carbon, air pollutants, mineral dust and sea salt based on the measurement of the aerosol extinction coefficient, backscatter coefficient and depolarization ratio. We are planning to make multi-year continuous Lidar observations. These observations will generate a 5-D aerosol distribution database used to develop a new data assimilation model. Based on this integrated analysis, it will be possible to provide a detailed aerosol re-analysis field covering all of Asia.

【Expected Research Achievements and Scientific Significance】 The integration of different research fields is an

important achievement of this research project. Ground-based and remote sensing measurements are combined with chemical transport models using data assimilation techniques, to produce an emissions inventory which is consistent between aerosol measurement and chemical transport modeling results. This new aerosol data assimilation method will provide accurate emission intensity estimate and correct aerosol distribution fields (database) necessary to study the impact of

aerosols on human health and global warming. Our research project is mainly linked to our new multi-wavelength lidar observation data, however, the proposed method can also use data from traditional ground-base monitoring stations, and is at the forefront of next generation research for simulating the atmospheric environment. Fig. 1 Schematic showing the integration of Lidar

measurement and data assimilation modeling

【Publications Relevant to the Project】・Nishizawa, T., N. Sugimoto et al.: Algorithms to

retrieve optical properties of three component aerosols from two-wavelength backscatter and one-wavelength polarization Lidar measurements considering nonsphericity of dust, J. Quantitative Spectroscopy & Radiative Transfer, 112, 254-267 (2010).

・ Yumimoto, K., I. Uno: Inverse estimate of long-term CO emission in China between 2005 – 2010 with Green’s function method, J. Jpn. Soc. Atmos. Environ., 47, 162-172 (2012)




Information】 http://www.riam.kyushu-u.ac.jp/taikai/index-e. html [email protected]

－68－


Title of Project： Research on Active Coordination Technology for Human Symbiotic Robot

Shigeki Sugano ( Waseda University, Faculty of Science and Engineering, Professor )

Research Area： Human informatics, Intelligent roboticsKeyword： Intelligent robot, Intelligent information processing

【Purpose and Background of the Research】 Labor shortages caused by aging society have

become a severe problem in developed countries. Because symbiotic robots can work with humans or support them in daily life, public and medical and welfare services, interest in human symbiotic robots has increased in these countries. These robots are expected to share a place at the same time with humans. Safety and work-efficiency are key issues for these robots. In the conventional framework of human symbiotic robots, it has been thought for long time that robots must avoid physical interactions with humans to ensure safety.

We consider this concept a major hurdle to enable robots to work efficiently with humans. Thus, we propose a shift of paradigm from: robots must avoid physical interactions with humans, to robots should actively coordinate with humans. We believe this paradigm shift can be a breakthrough to develop human symbiotic robots that are both safe and efficient. The purpose of this study is to establish a methodology to design mechanical structures and intelligent human symbiotic robots that coordinate actively with humans (Fig. 1).


This study can be divided into two major subjects. One is modeling the interaction between humans and robots both from a psychological and physiological (statics and dynamics) viewpoint. The second is to develop novel control theory and intelligence based on these models. We will validate experimentally these models using robots such as upper body humanoids with flexible manipulators and bipedal humanoid robot (Fig. 2). These investigations will be conducted in three major situations where interaction between humans and

robots occurs: (A) Weak contacts to teach one's direction. (B) Dynamic contacts for coordination (C) Actions to make a human to move


Scientific Significance】 There are a few studies on physical interactions

between humans and robots, especially active coordination between them. This study aims to establish a general methodology that can be used in various situations, whereas conventional studies in this field focus on a specific situation.

Once the methodology is established, it can be used in the design of various kinds of human symbiotic robots such as humanoid robots, human assisting devices, rehabilitation equipment and personal mobility systems.

【Publications Relevant to the Project】 H. Iwata and S. Sugano, “Design of human

symbiotic robot TWENDY-ONE,” in Proc. IEEE Int. Conf. Robotics and Automation (ICRA), pp. 580-586, 2009. Yo Kobayashi, Masakatsu G. Fujie, et al. , “Soft

interaction between body weight support system and human using fractional impedance Control”, Advanced Robotics, 26, pp. 1253-1269, 2012.




Information】http://www.sugano.mech.waseda.ac.jp/ http://www.twendyone.com/ http://www.takanishi.mech.waseda.ac.jp/ http://www.fujie.mech.waseda.ac.jp/

Figure 2 Research method

contact Modeling

Reconstruction

Figure 1 Research purpose


Title of Project： Five-dimensional data assimilation of aerosol based on integrated analysis of multi-wavelength lidar and chemical transport model

Itsushi Uno ( Kyushu University, Research Institute for Applied Mechanics, Professor )

Research Area： Environmental dynamic analysis, Environmental science Keyword： Lidar, aerosol, chemical transport model, data assimilation

【Purpose and Background of the Research】 Asia is one of the biggest emission sources of

atmospheric pollutants in the world. Besides anthropogenic emissions, this region is also a major source of pollutants from biomass burning. Sulfates and black carbon particles in the air control and accelerate global warming, respectively. Aerosols exists in the atmosphere for 1 – 2 weeks and shows large temporal and spatial variation. Because the potential of aerosols to contribute to global warming depends on their composition, particle diameter and vertical profiles, it is necessary to integrate field measurements with chemical transport models which contain detailed aerosol information.

【Research Methods】 We will observe atmospheric aerosols from the

main air pollutant sources in Asia using a newly developed multi-wavelength Lidar system located in three sites in Japan. This new Lidar system is designed to retrieve the composition of aerosols including black carbon, air pollutants, mineral dust and sea salt based on the measurement of the aerosol extinction coefficient, backscatter coefficient and depolarization ratio. We are planning to make multi-year continuous Lidar observations. These observations will generate a 5-D aerosol distribution database used to develop a new data assimilation model. Based on this integrated analysis, it will be possible to provide a detailed aerosol re-analysis field covering all of Asia.

【Expected Research Achievements and Scientific Significance】 The integration of different research fields is an

important achievement of this research project. Ground-based and remote sensing measurements are combined with chemical transport models using data assimilation techniques, to produce an emissions inventory which is consistent between aerosol measurement and chemical transport modeling results. This new aerosol data assimilation method will provide accurate emission intensity estimate and correct aerosol distribution fields (database) necessary to study the impact of

aerosols on human health and global warming. Our research project is mainly linked to our new multi-wavelength lidar observation data, however, the proposed method can also use data from traditional ground-base monitoring stations, and is at the forefront of next generation research for simulating the atmospheric environment. Fig. 1 Schematic showing the integration of Lidar

measurement and data assimilation modeling

【Publications Relevant to the Project】・Nishizawa, T., N. Sugimoto et al.: Algorithms to

retrieve optical properties of three component aerosols from two-wavelength backscatter and one-wavelength polarization Lidar measurements considering nonsphericity of dust, J. Quantitative Spectroscopy & Radiative Transfer, 112, 254-267 (2010).

・ Yumimoto, K., I. Uno: Inverse estimate of long-term CO emission in China between 2005 – 2010 with Green’s function method, J. Jpn. Soc. Atmos. Environ., 47, 162-172 (2012)




Information】 http://www.riam.kyushu-u.ac.jp/taikai/index-e. html [email protected]

－69－


Research (S)

【Grant-in-Aid for Scientific Research(S) Integrated Disciplines (Environmental science)

Title of Project: In vivo, in situ assessment of the mutagenic risk of radiation and environmental chemicals, using newly developed animal systems

Asao Noda ( Radiation Effects Research Foundation, Department of Genetics,

Assistant Department Chief ) Research Area: Environmental science, risk sciences of radiation and chemicals Keyword: Health effects, somatic mutation

【Purpose and Background of the Research】 Radiation and environmental chemicals affect

every cell and tissue in our body, but detailed risk assessment is not currently available. In this study, we develop model animal systems in which living mutant cells arising in the body become fluorescent (GFP positive) to allow the detection of mutant cells in an intact tissue structure. Apart from examination of preexisting systems, this approach enables measurement of the mutant frequencies in self-renewing somatic stem cells, as well as differentiation committed cell populations and functionally differentiated cells in situ after genotoxic insult. Thus the study provides a novel opportunity to estimate mutational risk in cancer-susceptible cell populations. 【Research Methods】

(1) The systems we use resemble a higher-animal version of the Ames Test. We develop cell systems in which reversion, or forward mutation, at a specific gene locus turns the cells “green” in mice and medaka killifish. The reversion system consists of partial duplication of the HPRT gene in conjunction with the GFP gene, so that deletion of one segment from the tandem duplicate produces HPRT-GFP fusion protein. The forward mutation system turns cells “green” with inactivating or dominant negative (gain-of-function) mutations at the oncogene or tumor suppressor gene. (2) The effects of fetal and childhood exposure are examined in various tissues in relation to different doses and the timing of individual development. Also, the genetic effects of radiation are monitored with germ cell mutations (spermatogonia cells and mature oocyte mutations).

(3) The effects of genetic background and somatic cell instability on offspring born to irradiated parents are examined. The molecular mechanisms of stem cell mutation in regenerating tissues are analyzed.

【Expected Research Achievements and Scientific Significance】 Detection and measurement of the mutagenic

risk of somatic cells in vivo, in a spatio-temporal manner, are prerequisites for contemporary risk assessment of environmental radiation and chemicals. For example, the risk of breast cancer development should be evaluated in mammary gland cells in vivo. Our model system will make such assessment possible. It should also be noted that genetic effects, i.e. transgenerational effects, are evaluated easily by measuring germ cell mutations. Low-dose and life-time chronic exposures, or the effects of internal exposure by radionuclides, are also challenging issues that this study addresses.

【Publications Relevant to the Project】・Noda A. et al., Mutat. Res. 721:101-107, 2011. ・Noda A. et al., J. Cell Sci. 125:5280-5287, 2012. ・Nakamura N. et al., Ann. Rev. Genet., in press.


Information】 http://www.rerf.jp/

Figure 1. Model animals

Figure 2. In vivo arising mutant cells Liver Pancreas


Title of Project： Comprehensive study on environmental electrophiles-mediated signal transduction pathways regulated by active sulfur species

Yoshito Kumagai ( University of Tsukuba, Faculty of Medicine, Professor )

Research Area： Environmental and hygienic pharmacyKeyword： environmental response, electrophile, chemical modification, signal transduction,

active sulfur species 【Purpose and Background of the Research】

Environmental electrophiles (EEs) covalently bind to thiol groups in proteins, such as sensor proteins, to form protein adducts, and this can lead to the development of cancer as well as injury to the surrounding tissue. However, very little is currently known about the mechanistic details of these phenomena and the role of EEs in these processes. A variety of different cellular signal transduction pathways are known to be associated with homeostasis and the failure of cellular signaling can result in a number of physiological problems. In the current study, we examine concentration-specific changes in the redox signal transduction pathways that are promoted by the activation of effecter molecules coupled to the chemical modification of a sensor protein following the reaction of its thiol groups with EEs. We also explore the possibility that active sulfur species (ASS) such as hydrogen sulfide, persulfide and polysulfide would negatively regulate EEs-mediated redox signaling processes.

【Research Methods】 As models for EEs, we use with 1,4-benzoquinone, 1,4-naphthoquinone, methylmercury, cadmium, lead, acetaldehyde and formaldehyde. We examine (1) the development of a convenient assay for the detection of covalent modifications to the cellular

proteins caused by their exposure to EEs; (2) the concentration-specificity during the activation and disruption of the signal transduction pathways following the exposure of cultured cells or experimental animals to EEs; (3) the impact of the negative regulation of the ASS on the EEs-dependent modulation of the redox signal transduction pathways; and (4) the beneficial effect of phytochemical extracts containing the ASS on the toxicities of EEs in wild-type and CSE (an enzyme responsible for production of such ASS) knockout mice.

【Expected Research Achievements and Scientific Significance】

Our rationale for this project is focused on our belief that EEs are capable of modifying sensor proteins by reacting with their thiol groups, and that this could result in structural changes, thereby activating (under lower exposure) and disrupting (under higher exposure) the redox signal transduction pathways. It is noteworthy that ASS react readily with EEs, leading to the loss of their reactivity.

【Publications Relevant to the Project】 1. Kumagai Y, Shinkai Y et al. The chemical

biology of naphthoquinones and its environmental implications. Annu Rev Pharmacol Toxicol 52: 221-247, 2012

2. Nishida M, Sawa T, Kumagai Y, Akaike T et al. Hydrogen sulfide anion regulates redox signaling via electrophile sulfhydration. Nature Chem Biol 8: 714-724, 2012.




Information】 http://www.md.tsukuba.ac.jp/environmental_ medicine/index.html

[email protected]

Fig.1 Modulation of environmental electrophiles-mediated the signal transduction pathways regulated by the active sulfur species

－70－

【Grant-in-Aid for Scientific Research(S) Integrated Disciplines (Environmental science)

Title of Project: In vivo, in situ assessment of the mutagenic risk of radiation and environmental chemicals, using newly developed animal systems

Asao Noda ( Radiation Effects Research Foundation, Department of Genetics,

Assistant Department Chief ) Research Area: Environmental science, risk sciences of radiation and chemicals Keyword: Health effects, somatic mutation

【Purpose and Background of the Research】 Radiation and environmental chemicals affect

every cell and tissue in our body, but detailed risk assessment is not currently available. In this study, we develop model animal systems in which living mutant cells arising in the body become fluorescent (GFP positive) to allow the detection of mutant cells in an intact tissue structure. Apart from examination of preexisting systems, this approach enables measurement of the mutant frequencies in self-renewing somatic stem cells, as well as differentiation committed cell populations and functionally differentiated cells in situ after genotoxic insult. Thus the study provides a novel opportunity to estimate mutational risk in cancer-susceptible cell populations. 【Research Methods】

(1) The systems we use resemble a higher-animal version of the Ames Test. We develop cell systems in which reversion, or forward mutation, at a specific gene locus turns the cells “green” in mice and medaka killifish. The reversion system consists of partial duplication of the HPRT gene in conjunction with the GFP gene, so that deletion of one segment from the tandem duplicate produces HPRT-GFP fusion protein. The forward mutation system turns cells “green” with inactivating or dominant negative (gain-of-function) mutations at the oncogene or tumor suppressor gene. (2) The effects of fetal and childhood exposure are examined in various tissues in relation to different doses and the timing of individual development. Also, the genetic effects of radiation are monitored with germ cell mutations (spermatogonia cells and mature oocyte mutations).

(3) The effects of genetic background and somatic cell instability on offspring born to irradiated parents are examined. The molecular mechanisms of stem cell mutation in regenerating tissues are analyzed.

【Expected Research Achievements and Scientific Significance】 Detection and measurement of the mutagenic

risk of somatic cells in vivo, in a spatio-temporal manner, are prerequisites for contemporary risk assessment of environmental radiation and chemicals. For example, the risk of breast cancer development should be evaluated in mammary gland cells in vivo. Our model system will make such assessment possible. It should also be noted that genetic effects, i.e. transgenerational effects, are evaluated easily by measuring germ cell mutations. Low-dose and life-time chronic exposures, or the effects of internal exposure by radionuclides, are also challenging issues that this study addresses.

【Publications Relevant to the Project】・Noda A. et al., Mutat. Res. 721:101-107, 2011. ・Noda A. et al., J. Cell Sci. 125:5280-5287, 2012. ・Nakamura N. et al., Ann. Rev. Genet., in press.


Information】 http://www.rerf.jp/

Figure 1. Model animals

Figure 2. In vivo arising mutant cells Liver Pancreas


Title of Project： Comprehensive study on environmental electrophiles-mediated signal transduction pathways regulated by active sulfur species

Yoshito Kumagai ( University of Tsukuba, Faculty of Medicine, Professor )

Research Area： Environmental and hygienic pharmacyKeyword： environmental response, electrophile, chemical modification, signal transduction,

active sulfur species 【Purpose and Background of the Research】

Environmental electrophiles (EEs) covalently bind to thiol groups in proteins, such as sensor proteins, to form protein adducts, and this can lead to the development of cancer as well as injury to the surrounding tissue. However, very little is currently known about the mechanistic details of these phenomena and the role of EEs in these processes. A variety of different cellular signal transduction pathways are known to be associated with homeostasis and the failure of cellular signaling can result in a number of physiological problems. In the current study, we examine concentration-specific changes in the redox signal transduction pathways that are promoted by the activation of effecter molecules coupled to the chemical modification of a sensor protein following the reaction of its thiol groups with EEs. We also explore the possibility that active sulfur species (ASS) such as hydrogen sulfide, persulfide and polysulfide would negatively regulate EEs-mediated redox signaling processes.

【Research Methods】 As models for EEs, we use with 1,4-benzoquinone, 1,4-naphthoquinone, methylmercury, cadmium, lead, acetaldehyde and formaldehyde. We examine (1) the development of a convenient assay for the detection of covalent modifications to the cellular

proteins caused by their exposure to EEs; (2) the concentration-specificity during the activation and disruption of the signal transduction pathways following the exposure of cultured cells or experimental animals to EEs; (3) the impact of the negative regulation of the ASS on the EEs-dependent modulation of the redox signal transduction pathways; and (4) the beneficial effect of phytochemical extracts containing the ASS on the toxicities of EEs in wild-type and CSE (an enzyme responsible for production of such ASS) knockout mice.


Our rationale for this project is focused on our belief that EEs are capable of modifying sensor proteins by reacting with their thiol groups, and that this could result in structural changes, thereby activating (under lower exposure) and disrupting (under higher exposure) the redox signal transduction pathways. It is noteworthy that ASS react readily with EEs, leading to the loss of their reactivity.

【Publications Relevant to the Project】 1. Kumagai Y, Shinkai Y et al. The chemical

biology of naphthoquinones and its environmental implications. Annu Rev Pharmacol Toxicol 52: 221-247, 2012

2. Nishida M, Sawa T, Kumagai Y, Akaike T et al. Hydrogen sulfide anion regulates redox signaling via electrophile sulfhydration. Nature Chem Biol 8: 714-724, 2012.




Information】 http://www.md.tsukuba.ac.jp/environmental_ medicine/index.html

[email protected]

Fig.1 Modulation of environmental electrophiles-mediated the signal transduction pathways regulated by the active sulfur species

－71－


Research (S)


Title of Project： Development of system dynamic model of plantation to evaluate the sustainable production of crops by appropriate recycle of biomass residues

Koichi Fujie ( Yokohama National University, Graduate School of Environment

and Information Sciences, Professor )

Research Area： Environmental science, Sustainable and environmental system developmentKeyword： Biomass utilization, recycling and LCA, sound material recycle system

【Purpose and Background of the Research】 System dynamic model to simulate the behavior of

plantation system will be developed to evaluate the optimal management with recycle of biomass residues. Information and experimentally observed data in various plantations in Sumatra will be used for the model development. The model can be used to simulate and evaluate the following factors; 1) Optimal management to increase the fertility of

the cultivation field by controlling the soil mineralization, and thus the yield of crops.

2) Development and evaluation of treatment and recycle system of various biomass residues to produce compost, livestock feed, biogas for energy, and electricity. And then,

3) Potential of plantation to supply energy and biomass for the local area after the captive use of them for the self-support local area.

【Research Methods】 Plantation system is catabolized into three zones

as shown in Fig.1. Zone-1 shows cultivation field of plantation where behavior of soil ecosystem such as bacteria, fungi, microbial grazer, litter transformers are investigated as well as the material flow analysis of carbon, nitrogen, and so on under tillage and no-tillage condition. Based on the observed results, organic degradation rate equation will be derived by the modification of Roth-C model.

Fig.1 Plantation system incorporated with recycles of biomass residues for captive and external use.

Zone-2 shows processing and refining of crops from plantation such as sugarcane, oil palm, cassava, etc. Material flow of carbon, nitrogen, phosphorus and potassium, and thus energy flow are analyzed by the site observation. The data will

be used to diagnose the condition of processes. Zone-3 shows the treatment and recycle of

biomass residues and of wastewater such as composting, anaerobic digestion, production of livestock feed, power generation and so on. Material flow and energy flow in those systems are investigated in the plantations.

By using the results in Zone-1 ～ 3, system dynamic model will developed to simulate the behavior of plantation system with recycle use of biomass residues toward sustainable production and for the reduction of environmental loading.

Fig.2 Development of organic carbon degradation

model based on modification Troth-C model. 【Expected Research Achievements and

Scientific Significance】 Appropriate management of soil and soil

ecosystem for environmental conservation type agriculture with sustainable production of crops in plantations is proposed based on the analyses of material and energy flow and behavior of soil ecosystem in various plantations. Procedure to design of sound recycle system of biomass residues in and outside plantation can be developed.

【Publications Relevant to the Project】・H. Kamahara, U. Hasanudin, K. Fujie, et al.,

Improvement Potential for Net Energy Balance of BDF Derived from Palm Oil: A Case Study from Indonesian Practice, BIOMASS AND BIOENERGY, 34, 1818-1824(2010)

・M. Hanif, Y. Atsuta, K. Fujie, H. Daimon, Supercritical Fluid Extraction and UPLC of Respiratory Quinones for Microbial Community Analysis in Environmental and Biological Samples, Molecules, 17,2628-2642 (2012)

【Term of Project】FY2013 - 2016 【Budget Allocation】98,200 Thousand Yen 【Homepage Address and Other Contact

Information】 http://www.envlab.ynu.ac.jp/ [email protected]

【Grant-in-Aid for Scientific Research(S)】 Integrated Disciplines (Complex systems)

Title of Project： Integrating dryland disaster science

Masao Shinoda ( Tottori University, Arid Land Research Center, Professor )

Research Area： Geography Keyword： Natural disaster, Drought, Desertification, Dust, Dryland

【Purpose and Background of the Research】 Drylands occupy 41% of Earth’s land area and are

home to more than 2 billion people—a third of the human population in the year 2000. The large proportion is the poor, forming the Bottom of the Pyramid. The nature-society system is among the most vulnerable to projected increasing frequency of various extreme weathers. Especially, drylands in middle-high latitudes have a severe environment coupled with an arid and cold climate and the livelihood has been jeopardized repeatedly by natural disasters that occur in such a climate. The disasters are characterized by so-called 4D (i.e., drought, dzud, dust storm, and desertification; Fig. 1) that occur interactively. However, previous approaches towards elucidating disaster mechanisms and implementing the management have not fully been integrated, as they only dealt with each disaster separately.

Given this background, the present project aims (1) to relate the 4D disasters in the dry inland area of Eurasia to each other in terms of causal mechanisms (especially, drought memory) and the time scales of their occurrence and (2) to develop comprehensive proactive countermeasures and make a policy recommendation for mitigating multi-disaster impacts.

【Research Methods】 Objective 1 can be achieved by correlating

impacts of 4D-producing extreme weathers in terms of the concept of drought memory and by evaluating risks for each disaster as the product of impact (hazard or forcing) and vulnerability (expressed by three elements of exposure, sensitivity, and resilience) of the nature-society system (Fig. 2). Objective 2 can be achieved by implementing approaches integrating countermeasure opinions to reduce the vulnerability.


Scientific Significance】 Expected achievements are (1) prediction of 4D

disasters based on integrated risk assessment and (2) policy recommendation of proactive disaster management with countermeasure options.

【Publications Relevant to the Project】 Shinoda, M.: Land: Proactive Management of Drought and Its Derived Disasters. In R. Shaw and T. Phong eds.: Environment Disaster Linkages. Community, Environment and Disaster Risk Management, Vol. 9, Emerald Publishers, Bingley UK, 61-78, January 2012.




Information】 http://www.alrc.tottori-u.ac.jp/japanese/ organization/shinoda.pdf

Figure 2 How are 4D interrelated?

Figure 1 4D disasters in arid Eurasia (dust storm, S. Otani; drought, T. Ito; desertification, N. Yamanaka)

－72－


Title of Project： Development of system dynamic model of plantation to evaluate the sustainable production of crops by appropriate recycle of biomass residues

Koichi Fujie ( Yokohama National University, Graduate School of Environment

and Information Sciences, Professor )

Research Area： Environmental science, Sustainable and environmental system developmentKeyword： Biomass utilization, recycling and LCA, sound material recycle system

【Purpose and Background of the Research】 System dynamic model to simulate the behavior of

plantation system will be developed to evaluate the optimal management with recycle of biomass residues. Information and experimentally observed data in various plantations in Sumatra will be used for the model development. The model can be used to simulate and evaluate the following factors; 1) Optimal management to increase the fertility of

the cultivation field by controlling the soil mineralization, and thus the yield of crops.

2) Development and evaluation of treatment and recycle system of various biomass residues to produce compost, livestock feed, biogas for energy, and electricity. And then,

3) Potential of plantation to supply energy and biomass for the local area after the captive use of them for the self-support local area.

【Research Methods】 Plantation system is catabolized into three zones

as shown in Fig.1. Zone-1 shows cultivation field of plantation where behavior of soil ecosystem such as bacteria, fungi, microbial grazer, litter transformers are investigated as well as the material flow analysis of carbon, nitrogen, and so on under tillage and no-tillage condition. Based on the observed results, organic degradation rate equation will be derived by the modification of Roth-C model.

Fig.1 Plantation system incorporated with recycles of biomass residues for captive and external use.

Zone-2 shows processing and refining of crops from plantation such as sugarcane, oil palm, cassava, etc. Material flow of carbon, nitrogen, phosphorus and potassium, and thus energy flow are analyzed by the site observation. The data will

be used to diagnose the condition of processes. Zone-3 shows the treatment and recycle of

biomass residues and of wastewater such as composting, anaerobic digestion, production of livestock feed, power generation and so on. Material flow and energy flow in those systems are investigated in the plantations.

By using the results in Zone-1 ～ 3, system dynamic model will developed to simulate the behavior of plantation system with recycle use of biomass residues toward sustainable production and for the reduction of environmental loading.

Fig.2 Development of organic carbon degradation

model based on modification Troth-C model. 【Expected Research Achievements and

Scientific Significance】 Appropriate management of soil and soil

ecosystem for environmental conservation type agriculture with sustainable production of crops in plantations is proposed based on the analyses of material and energy flow and behavior of soil ecosystem in various plantations. Procedure to design of sound recycle system of biomass residues in and outside plantation can be developed.

【Publications Relevant to the Project】・H. Kamahara, U. Hasanudin, K. Fujie, et al.,

Improvement Potential for Net Energy Balance of BDF Derived from Palm Oil: A Case Study from Indonesian Practice, BIOMASS AND BIOENERGY, 34, 1818-1824(2010)

・M. Hanif, Y. Atsuta, K. Fujie, H. Daimon, Supercritical Fluid Extraction and UPLC of Respiratory Quinones for Microbial Community Analysis in Environmental and Biological Samples, Molecules, 17,2628-2642 (2012)

【Term of Project】FY2013 - 2016 【Budget Allocation】98,200 Thousand Yen 【Homepage Address and Other Contact

Information】 http://www.envlab.ynu.ac.jp/ [email protected]


Title of Project： Integrating dryland disaster science

Masao Shinoda ( Tottori University, Arid Land Research Center, Professor )

Research Area： Geography Keyword： Natural disaster, Drought, Desertification, Dust, Dryland

【Purpose and Background of the Research】 Drylands occupy 41% of Earth’s land area and are

home to more than 2 billion people—a third of the human population in the year 2000. The large proportion is the poor, forming the Bottom of the Pyramid. The nature-society system is among the most vulnerable to projected increasing frequency of various extreme weathers. Especially, drylands in middle-high latitudes have a severe environment coupled with an arid and cold climate and the livelihood has been jeopardized repeatedly by natural disasters that occur in such a climate. The disasters are characterized by so-called 4D (i.e., drought, dzud, dust storm, and desertification; Fig. 1) that occur interactively. However, previous approaches towards elucidating disaster mechanisms and implementing the management have not fully been integrated, as they only dealt with each disaster separately.

Given this background, the present project aims (1) to relate the 4D disasters in the dry inland area of Eurasia to each other in terms of causal mechanisms (especially, drought memory) and the time scales of their occurrence and (2) to develop comprehensive proactive countermeasures and make a policy recommendation for mitigating multi-disaster impacts.

【Research Methods】 Objective 1 can be achieved by correlating

impacts of 4D-producing extreme weathers in terms of the concept of drought memory and by evaluating risks for each disaster as the product of impact (hazard or forcing) and vulnerability (expressed by three elements of exposure, sensitivity, and resilience) of the nature-society system (Fig. 2). Objective 2 can be achieved by implementing approaches integrating countermeasure opinions to reduce the vulnerability.


Scientific Significance】 Expected achievements are (1) prediction of 4D

disasters based on integrated risk assessment and (2) policy recommendation of proactive disaster management with countermeasure options.

【Publications Relevant to the Project】 Shinoda, M.: Land: Proactive Management of Drought and Its Derived Disasters. In R. Shaw and T. Phong eds.: Environment Disaster Linkages. Community, Environment and Disaster Risk Management, Vol. 9, Emerald Publishers, Bingley UK, 61-78, January 2012.




Information】 http://www.alrc.tottori-u.ac.jp/japanese/ organization/shinoda.pdf

Figure 2 How are 4D interrelated?

Figure 1 4D disasters in arid Eurasia (dust storm, S. Otani; drought, T. Ito; desertification, N. Yamanaka)

－73－


Research (S)


Title of Project： Development of Behavioral Disaster Management

Haruo Hayashi ( Kyoto University, Disaster Prevention Research Institute, Professor )

Research Area： Complex systems Keyword： Crisis management, Social technology for security(evacuation, mass guidance,

information distribution, hazard map) 【Purpose and Background of the Research】

In this study, we aim to establish a new discipline called “Behavioral Disaster Management” to improve disaster resilience. By developing a theory of human decision making process based on “bounded rationality” in the context of disaster mitigation, preparedness, response and recovery.

The purpose of this study is to promote multi-disciplinary research for reducing disaster risk and curbing losses through knowledge-based human actions by understanding decision-making in complex and changing risk contexts in general. In particular, this study focuses on the reduction of human casualty due to strong shaking, tsunami, and fire caused by an anticipated “Nankai Trough earthquakes” which anticipate a total of more than 320,000 casualties in the worst case scenario.


BoundedRationality

Appropriate Safety Actions

Risk Communication

DecisionMaking

Cognitive

Holistic Disaster Impact Assessment

CulturalConstraints

ImpactSimulation

SocialInfrastructure

SocialSocio-

economicSystems

Multi-hazardSimulation

NaturalDisaster

MechanismHazard

Monitoring

In this study, five research domains will be set

to promote interdisciplinary reach. (1) Development of quantitative behavioral and attitudinal measurement system to evaluate whether people may or can take appropriate safety actions; (2) Development of theory of decision making based on both bounded rationality and cultural constraints; (3) Development of holistic disaster impact

assessment methods to integrate damages to social infrastructure and damages to socio-economic systems: (4) Development of multi-hazard simulation method to reflect disaster mechanisams based on continuous hazard monitoring data; and (5) Development of information integuration methods of achievements from the abovementioned four domains using web-GIS “Masy-up” technologies.

【Expected Research Achievements and Scientific Significance】 A clear example of disaster reduction would be

the contribution to decrease the preventable deaths due to the tsunami attack accompanied by anticipated Nankai Trough earthquake. A total of 230,000 people would be killed by tsunami in the worst case scenario. By applying structural mitigation measures, expected loss reduction would be by 85,000. Immediate evacuation, as an example of appropriate human behavior, may reduce casualty by 105,000 or more.

Worst case 242,000

Levee/Water Gate224,000

Evacuation Building157,000

Immediate Evacuation85,000


(－190,000)

－67,000

－18,000

（－85,000）－105,000

－139,000

－33,000

(－157,000)

From：Cabinet Office,Disaster Management Section Report

Tsunami Casualties

Figure 2, Tsunami Casualty Reduction

【Publications Relevant to the Project】

Kahneman, D. "Thinking, Fast and Slow”, Farrar Straus & Giroux, 2011


Information】 http://www.drs.dpri.kyoto-u.ac.jp/hayashi/ [email protected]

Figure 1 Research paradigm


Title of Project： Design of Novel Biomaterials which Scavenge Reactive Oxygen Species and Their Applications

Yukio Nagasaki ( University of Tsukuba, Faculty of Pure and Applied Sciences,

Professor )

Research Area： Biomedical engineering/ Biological material scienceKeyword： Biomaterials, Nanobiomaterials, Drug Delivery System

【Purpose and Background of the Research】 When materials are applied to living body as

biomaterials, medical devices or artificial organs, they cause versatile responses. One of the most significant phenomena between material and living body interaction is generation of reactive oxygen species (ROS). ROS are known to play versatile roles on the occasion of many important events in vivo. However excessive production of ROS causes significant adverse effects to living body. In this project, we are focusing on design of new polymeric materials, which scavenge ROS. For this objective, nitroxide radical is employed as a catalytic center. Several types of nitroxide radical polymers (redox polymers, Fig. 1) will be designed and investigated their functionality in vitro and in vivo.

【Research Methods】 We have so far prepared amphiphilic block

copolymers possessing nitroxide radicals as a side chain of its hydrophobic segment, which spontaneously form core-shell type polymeric micelle under physiological conditions. The redox nanoparticle (RNP) thus obtained have confirmed to work as in vivo ROS scavenger for several types of diseases such as cerebral and renal ischemia reperfusion injuries and ulcerative colitis. In this project, we will further study these redox polymers not only as nanomedicines for other oxidative stress-related diseases but also as other biomaterials. Redox polymer micelle mentioned above will be applied for several chronic diseases such as arteriosclerosis, non-alcoholic steatohepatitis, rheumatism and Alzheimer’s diseases. We will design new redox injectable gel for periodontal disease and joint inflammation. The gel formation properties improve local retention of

these materials and long-term scavenge of ROS. Silica-installed RNP (siRNP) will be prepared for peritoneal dialysis and bioadsorbents. Silica increases absorption capacity of low molecualar wright wastes in addition to the ROS scavenging ability. Surface modification by redox polymers will be investigated for non-biofouling and cell culture surfaces.


Scientific Significance】 Important point of this work is to explore how

nitroxide radical containing polymer works as nanomedicines and also as biomaterilas. Because it is not low molecular weight drugs, distribution of these materials in vivo is significantly different. Since they are not internalized in mitochondria in cell, for example, they do not interfere the normal mitochondrial electron transport chain, which is important energy production process in vivo. Since activation of bio-components such as proteins, cells and tissues often occurs when contact with materials, the ROS scavenging polymers are also promising as biomaterials including surface modification agents. Several types of novel biomaterials including nanomedicines will be anticipated in this project.

【Publications Relevant to the Project】・Long Binh Vong, et al., An Orally Administered Redox

Nanoparticle that Accumlates in the Colonic Mucosa and Reduces Colitis in Mice, Gastroenterology, Vol.143, No.4, 1027-1036(2012).

・Yukio Nagasaki, Nitroxide radicals and nanoparticles: A partnership for nanomedicine radical delivery, Therapeutic Delivery, 3(2) 1-15(2012)




Information】 http://www.ims.tsukuba.ac.jp/~nagasaki_lab/index.htm

[RR’NO+] + O2・- → RR’NO・ + O2　　

RR’NO・ + O2・- + 2H+ →　 [RR’NO+] + H2O2　

RR’NO・ + X・　→　RR’NOX RR’NOH + X・ → RR’NO・ +XH　　

Figure 1. Design of redox reactive polymers

－74－


Title of Project： Development of Behavioral Disaster Management

Haruo Hayashi ( Kyoto University, Disaster Prevention Research Institute, Professor )

Research Area： Complex systems Keyword： Crisis management, Social technology for security(evacuation, mass guidance,

information distribution, hazard map) 【Purpose and Background of the Research】

In this study, we aim to establish a new discipline called “Behavioral Disaster Management” to improve disaster resilience. By developing a theory of human decision making process based on “bounded rationality” in the context of disaster mitigation, preparedness, response and recovery.

The purpose of this study is to promote multi-disciplinary research for reducing disaster risk and curbing losses through knowledge-based human actions by understanding decision-making in complex and changing risk contexts in general. In particular, this study focuses on the reduction of human casualty due to strong shaking, tsunami, and fire caused by an anticipated “Nankai Trough earthquakes” which anticipate a total of more than 320,000 casualties in the worst case scenario.


BoundedRationality

Appropriate Safety Actions

Risk Communication

DecisionMaking

Cognitive

Holistic Disaster Impact Assessment

CulturalConstraints

ImpactSimulation

SocialInfrastructure

SocialSocio-

economicSystems

Multi-hazardSimulation

NaturalDisaster

MechanismHazard

Monitoring

In this study, five research domains will be set

to promote interdisciplinary reach. (1) Development of quantitative behavioral and attitudinal measurement system to evaluate whether people may or can take appropriate safety actions; (2) Development of theory of decision making based on both bounded rationality and cultural constraints; (3) Development of holistic disaster impact

assessment methods to integrate damages to social infrastructure and damages to socio-economic systems: (4) Development of multi-hazard simulation method to reflect disaster mechanisams based on continuous hazard monitoring data; and (5) Development of information integuration methods of achievements from the abovementioned four domains using web-GIS “Masy-up” technologies.

【Expected Research Achievements and Scientific Significance】 A clear example of disaster reduction would be

the contribution to decrease the preventable deaths due to the tsunami attack accompanied by anticipated Nankai Trough earthquake. A total of 230,000 people would be killed by tsunami in the worst case scenario. By applying structural mitigation measures, expected loss reduction would be by 85,000. Immediate evacuation, as an example of appropriate human behavior, may reduce casualty by 105,000 or more.

Worst case 242,000

Levee/Water Gate224,000

Evacuation Building157,000



(－190,000)

－67,000

－18,000

（－85,000）－105,000

－139,000

－33,000

(－157,000)

From：Cabinet Office,Disaster Management Section Report

Tsunami Casualties

Figure 2, Tsunami Casualty Reduction

【Publications Relevant to the Project】

Kahneman, D. "Thinking, Fast and Slow”, Farrar Straus & Giroux, 2011


Information】 http://www.drs.dpri.kyoto-u.ac.jp/hayashi/ [email protected]

Figure 1 Research paradigm


Title of Project： Design of Novel Biomaterials which Scavenge Reactive Oxygen Species and Their Applications

Yukio Nagasaki ( University of Tsukuba, Faculty of Pure and Applied Sciences,

Professor )

Research Area： Biomedical engineering/ Biological material scienceKeyword： Biomaterials, Nanobiomaterials, Drug Delivery System

【Purpose and Background of the Research】 When materials are applied to living body as

biomaterials, medical devices or artificial organs, they cause versatile responses. One of the most significant phenomena between material and living body interaction is generation of reactive oxygen species (ROS). ROS are known to play versatile roles on the occasion of many important events in vivo. However excessive production of ROS causes significant adverse effects to living body. In this project, we are focusing on design of new polymeric materials, which scavenge ROS. For this objective, nitroxide radical is employed as a catalytic center. Several types of nitroxide radical polymers (redox polymers, Fig. 1) will be designed and investigated their functionality in vitro and in vivo.

【Research Methods】 We have so far prepared amphiphilic block

copolymers possessing nitroxide radicals as a side chain of its hydrophobic segment, which spontaneously form core-shell type polymeric micelle under physiological conditions. The redox nanoparticle (RNP) thus obtained have confirmed to work as in vivo ROS scavenger for several types of diseases such as cerebral and renal ischemia reperfusion injuries and ulcerative colitis. In this project, we will further study these redox polymers not only as nanomedicines for other oxidative stress-related diseases but also as other biomaterials. Redox polymer micelle mentioned above will be applied for several chronic diseases such as arteriosclerosis, non-alcoholic steatohepatitis, rheumatism and Alzheimer’s diseases. We will design new redox injectable gel for periodontal disease and joint inflammation. The gel formation properties improve local retention of

these materials and long-term scavenge of ROS. Silica-installed RNP (siRNP) will be prepared for peritoneal dialysis and bioadsorbents. Silica increases absorption capacity of low molecualar wright wastes in addition to the ROS scavenging ability. Surface modification by redox polymers will be investigated for non-biofouling and cell culture surfaces.


Scientific Significance】 Important point of this work is to explore how

nitroxide radical containing polymer works as nanomedicines and also as biomaterilas. Because it is not low molecular weight drugs, distribution of these materials in vivo is significantly different. Since they are not internalized in mitochondria in cell, for example, they do not interfere the normal mitochondrial electron transport chain, which is important energy production process in vivo. Since activation of bio-components such as proteins, cells and tissues often occurs when contact with materials, the ROS scavenging polymers are also promising as biomaterials including surface modification agents. Several types of novel biomaterials including nanomedicines will be anticipated in this project.

【Publications Relevant to the Project】・Long Binh Vong, et al., An Orally Administered Redox

Nanoparticle that Accumlates in the Colonic Mucosa and Reduces Colitis in Mice, Gastroenterology, Vol.143, No.4, 1027-1036(2012).

・Yukio Nagasaki, Nitroxide radicals and nanoparticles: A partnership for nanomedicine radical delivery, Therapeutic Delivery, 3(2) 1-15(2012)




Information】 http://www.ims.tsukuba.ac.jp/~nagasaki_lab/index.htm

[RR’NO+] + O2・- → RR’NO・ + O2　　

RR’NO・ + O2・- + 2H+ →　 [RR’NO+] + H2O2　

RR’NO・ + X・　→　RR’NOX RR’NOH + X・ → RR’NO・ +XH　　

Figure 1. Design of redox reactive polymers

Integrated Disciplines (Complex systems)

－75－


Research (S)


Title of Project： Creation of Biomaterials Endowed with Unique Properties of DNA Soft-Interfaces

Mizuo Maeda ( RIKEN, Bioengineering Laboratory, Chief Scientist )

Research Area： Biomaterials Keyword： Nucleic Acid, Cell, Biomaterial, Gel, Soft-interface

【Purpose and Background of the Research】 The project aims to develop biomaterials using unique properties of DNA brushes (DNA soft-interfaces). We have demonstrated that the colloidal stability of the nanoparticles (NPs) having a double-stranded (ds) DNA soft-interface increases as decreasing thermodynamic stability of the terminal base pair. When complementary DNA is added to the dispersion of DNA–NPs to form the fully matched dsDNA, the NPs spontaneously aggregate in a non-crosslinking manner. In contrast, the dsDNA–NPs acquire high stability to disperse even in a high ionic-strength medium when a terminal mismatch exists at the interface between the dsDNA shell and water. This observation suggests that using small DNA (10–20 bases) as a surface modifier will allow us to regulate the properties of the materials by changing the terminal base pairs. We will verify this hypothesis by conducting the following three research topics.

【Research Methods】 Structural changes of DNA-nanorods One-dimensional arrays of DNA–gold NPs at regular intervals on a long DNA template are prepared. A dynamic change from such a beads-on-a-string structure into a rod-like one will be demonstrated by utilizing non-crosslinking aggregation of aligned dsDNA–gold NPs. This pseudo-nanorod will find various applications including gene carriers and structural models of chromatin.

DNA-gels exhibiting stimuli-responses Non-crosslinking aggregation of NPs is triggered within hydrogels to produce macroscopic responses such as volume changes. The gels are prepared through hybridization of DNA–NPs and DNA-grafted polymers. This responsiveness should be useful to develop biosensors and drug carriers.

Cell-culturing substrates with DNA layers Interactions are investigated between DNA soft-interfaces and proteins. We will elucidate a relationship between the structure of the terminal base pair and the degree of protein adsorption to design novel cell-culturing substrates with the DNA soft-interfaces. In addition, we will develop new DNA soft-interfaces whose surface properties can undergo drastic changes in response to stimuli, thereby constructing non-invasive cell harvesting systems.


Applications of the DNA soft-interfaces have been limited to the realm of analytical science and diagnostics. In this project, we will demonstrate the usefulness of the DNA soft-interfaces in the biomaterials field. Integrating analytical and materials sciences concerning the DNA soft-interfaces, we might possibly establish a new research area, “DNA interface engineering.” This emerging field should serve to further widen scientific avenues connecting bioconjugate chemistry, soft matter physics, cell biology, and nanotechnology.

【Publications Relevant to the Project】 1) K. Sato et al., J. Am. Chem. Soc. 2003, 125,

8102. 2) J. Nakanishi et al., J. Am. Chem. Soc. 2007,

129, 6694. 3) K. Suzuki et al., J. Am. Chem. Soc. 2009, 131,

7518.



【Homepage Address and Other Contact Information】 http:// www.riken.jp/lab-www/bioengineering/


Title of Project： Dynamics of molecular pattern recognition in protein interaction

Takao Hamakubo ( The University of Tokyo, Research Center for Advanced Science

and Technology, Professor )

Research Area： Biomolecular chemistryKeyword： Molecular mechanism of activity expression

【Purpose and Background of the Research】 Since the comprehensive of genomic or proteomic

analyses have revealed the networks of protein complexes, growing attention has been paid to the protein interactions involved in epigenetic regulation or post-translational modification. We have developed a method to generate specific monoclonal antibodies against target proteins and identified protein complexes that play important roles in the regulation of transcription or the cell-cycle. We have also identified pentraxin 3 (PTX3)-associating proteins in the blood of patients with sepsis, and found that PTX3, classified as a soluble pattern-recognition receptor known to bind pathogens or complement proteins, binds to neutrophil extracellular traps (NETs) components (Fig.1). Many proteins have been shown to interact with PTX3, but the molecular pattern of recognition has not yet been elucidated.

The aim of this project is to develop a screening method for a new therapeutic approach for intractable diseases such as cancer and severe sepsis by analyzing the mechanism of protein-protein or protein-RNA interactions.

【Research Methods】 Proteins undergo conformational changes upon

interaction, which is essential in the signal transduction or protein activation. Analysis of the mechanism of interaction and identification of hotspots of interacting surfaces are thus important for designing drugs that acts as inhibitors of protein-protein interactions. In this study, we focus on the interaction of PTX3 with its interacting proteins in order to identify the dynamic mechanism of interaction using structural analysis combined with computer simulation. We attempt to raise antibodies that fix the conformation of such proteins in their active or inactive form for

structural study. We also focus on Wilms’ tumor-1-associated protein (WTAP), which we identified as a regulator of the cell-cycle and recently determined its role on the RNA processing in combination with a set of associating proteins. In this study, we analyze the mechanism of this RNA processing in terms of structural aspects using computer simulation technique. From these results, we will attempt to understand how the molecule recognizes its interacting partners.


Although the sepsis is the leading cause of death in the ICU in developed countries, there is no efficacious therapy. This study should provide a possible candidate of drug by analyzing the relation between innate immunity and sepsis. The method of structural study with computer simulation should shed light on the mechanism of dynamic molecular interaction and provide a method of screening inhibitors of protein-protein interactions.

【Publications Relevant to the Project】・Daigo K, Hamakubo T et al. The proteomic

profile of circulating pentraxin 3 (PTX3) complex in sepsis demonstrates the interaction with azurocidin 1 and other components of neutrophil extracellular traps. Mol Cell Proteomics. 11(6): M111.015073, 2012.

・Horiuchi K, Hamakubo T et al. Wilms' tumor 1-associating protein regulates G2/M transition through stabilization of cyclin A2 mRNA. Proc Natl Acad Sci U S A. 103(46):17278-83. 2006




Information】 http:// qbm.rcast.u-tokyo.ac.jp

[email protected]

Fig. 1 PTX3 complex in sepsis

－76－


Title of Project： Creation of Biomaterials Endowed with Unique Properties of DNA Soft-Interfaces

Mizuo Maeda ( RIKEN, Bioengineering Laboratory, Chief Scientist )

Research Area： Biomaterials Keyword： Nucleic Acid, Cell, Biomaterial, Gel, Soft-interface

【Purpose and Background of the Research】 The project aims to develop biomaterials using unique properties of DNA brushes (DNA soft-interfaces). We have demonstrated that the colloidal stability of the nanoparticles (NPs) having a double-stranded (ds) DNA soft-interface increases as decreasing thermodynamic stability of the terminal base pair. When complementary DNA is added to the dispersion of DNA–NPs to form the fully matched dsDNA, the NPs spontaneously aggregate in a non-crosslinking manner. In contrast, the dsDNA–NPs acquire high stability to disperse even in a high ionic-strength medium when a terminal mismatch exists at the interface between the dsDNA shell and water. This observation suggests that using small DNA (10–20 bases) as a surface modifier will allow us to regulate the properties of the materials by changing the terminal base pairs. We will verify this hypothesis by conducting the following three research topics.

【Research Methods】 Structural changes of DNA-nanorods One-dimensional arrays of DNA–gold NPs at regular intervals on a long DNA template are prepared. A dynamic change from such a beads-on-a-string structure into a rod-like one will be demonstrated by utilizing non-crosslinking aggregation of aligned dsDNA–gold NPs. This pseudo-nanorod will find various applications including gene carriers and structural models of chromatin.

DNA-gels exhibiting stimuli-responses Non-crosslinking aggregation of NPs is triggered within hydrogels to produce macroscopic responses such as volume changes. The gels are prepared through hybridization of DNA–NPs and DNA-grafted polymers. This responsiveness should be useful to develop biosensors and drug carriers.

Cell-culturing substrates with DNA layers Interactions are investigated between DNA soft-interfaces and proteins. We will elucidate a relationship between the structure of the terminal base pair and the degree of protein adsorption to design novel cell-culturing substrates with the DNA soft-interfaces. In addition, we will develop new DNA soft-interfaces whose surface properties can undergo drastic changes in response to stimuli, thereby constructing non-invasive cell harvesting systems.


Applications of the DNA soft-interfaces have been limited to the realm of analytical science and diagnostics. In this project, we will demonstrate the usefulness of the DNA soft-interfaces in the biomaterials field. Integrating analytical and materials sciences concerning the DNA soft-interfaces, we might possibly establish a new research area, “DNA interface engineering.” This emerging field should serve to further widen scientific avenues connecting bioconjugate chemistry, soft matter physics, cell biology, and nanotechnology.

【Publications Relevant to the Project】 1) K. Sato et al., J. Am. Chem. Soc. 2003, 125,

8102. 2) J. Nakanishi et al., J. Am. Chem. Soc. 2007,

129, 6694. 3) K. Suzuki et al., J. Am. Chem. Soc. 2009, 131,

7518.



【Homepage Address and Other Contact Information】 http:// www.riken.jp/lab-www/bioengineering/


Title of Project： Dynamics of molecular pattern recognition in protein interaction

Takao Hamakubo ( The University of Tokyo, Research Center for Advanced Science

and Technology, Professor )

Research Area： Biomolecular chemistryKeyword： Molecular mechanism of activity expression

【Purpose and Background of the Research】 Since the comprehensive of genomic or proteomic

analyses have revealed the networks of protein complexes, growing attention has been paid to the protein interactions involved in epigenetic regulation or post-translational modification. We have developed a method to generate specific monoclonal antibodies against target proteins and identified protein complexes that play important roles in the regulation of transcription or the cell-cycle. We have also identified pentraxin 3 (PTX3)-associating proteins in the blood of patients with sepsis, and found that PTX3, classified as a soluble pattern-recognition receptor known to bind pathogens or complement proteins, binds to neutrophil extracellular traps (NETs) components (Fig.1). Many proteins have been shown to interact with PTX3, but the molecular pattern of recognition has not yet been elucidated.

The aim of this project is to develop a screening method for a new therapeutic approach for intractable diseases such as cancer and severe sepsis by analyzing the mechanism of protein-protein or protein-RNA interactions.

【Research Methods】 Proteins undergo conformational changes upon

interaction, which is essential in the signal transduction or protein activation. Analysis of the mechanism of interaction and identification of hotspots of interacting surfaces are thus important for designing drugs that acts as inhibitors of protein-protein interactions. In this study, we focus on the interaction of PTX3 with its interacting proteins in order to identify the dynamic mechanism of interaction using structural analysis combined with computer simulation. We attempt to raise antibodies that fix the conformation of such proteins in their active or inactive form for

structural study. We also focus on Wilms’ tumor-1-associated protein (WTAP), which we identified as a regulator of the cell-cycle and recently determined its role on the RNA processing in combination with a set of associating proteins. In this study, we analyze the mechanism of this RNA processing in terms of structural aspects using computer simulation technique. From these results, we will attempt to understand how the molecule recognizes its interacting partners.


Although the sepsis is the leading cause of death in the ICU in developed countries, there is no efficacious therapy. This study should provide a possible candidate of drug by analyzing the relation between innate immunity and sepsis. The method of structural study with computer simulation should shed light on the mechanism of dynamic molecular interaction and provide a method of screening inhibitors of protein-protein interactions.

【Publications Relevant to the Project】・Daigo K, Hamakubo T et al. The proteomic

profile of circulating pentraxin 3 (PTX3) complex in sepsis demonstrates the interaction with azurocidin 1 and other components of neutrophil extracellular traps. Mol Cell Proteomics. 11(6): M111.015073, 2012.

・Horiuchi K, Hamakubo T et al. Wilms' tumor 1-associating protein regulates G2/M transition through stabilization of cyclin A2 mRNA. Proc Natl Acad Sci U S A. 103(46):17278-83. 2006




Information】 http:// qbm.rcast.u-tokyo.ac.jp

[email protected]

Fig. 1 PTX3 complex in sepsis

－77－


Research (S)


Title of Project： Exploration of Novel Markers on Cancer and Development of a Technology for the Diagnosis Utilized by Comprehensive Glycomics

Shin-Ichiro Nishimura ( Hokkaido University, Faculty of Advanced Life Science, Professor )

Research Area： Complex systems Keyword： Searching diagnosis chemicals

【Purpose and Background of the Research】 Serum biomarkers are important to detect

diseases in early stage and useful for decision of treatment easily and quickly. In this study we will focus on gastrointestinal cancers including hepatocellular carcinoma, pancreatic cancer and colon cancer, and urological cancers including renal cell carcinoma and prostate cancer, to explore highly sensitive- and disease/pathologically specific- biomarkers by means of novel, large scale and comprehensive glycomics approach. We have developed automated system for pre-treatment and glycoblotting, ‘‘Sweetblot” (Japan Science and Technology Agency JST, 2003-2011). Utilized by the system, we will construct a highly reliable database of patients’ glycans, which allows us to explore glycobiomarkers with clinical information provided from longitudinal/cross-sectional studies. It is believed to enable us to achieve practical study for clinical applications.

【Research Methods】 “SweetBlot” is an automated system, which

utilizes glycoblotting method (Angew. Chem. Int. Ed. 2005, 44, 91-96), allowing us to enrich glycans specifically from crude mixtures from biological materials, such as serum. Once we set 10 L of serum onto 96-well micro plate, extraction, modification, label with tag, spot onto a target plate and analysis by MALDI-TOF/MS will be perfoemed automatically. Glycan profiles from 96 patients will be obtained in almost a day.

Here we will apply 200-300 samples from patients in each region of disease, including serum, urine, tissues and cultured cells, to “Sweetblot”. We will analyze the samples which are sequentially obtained from the same individuals, and also from the same disease patients in the distinct hospitals. Potential glycan biomarkers will be found from the accumulated glycan data, which will provide us the efficiency of medicines and/or prognosis, following to an evaluation by comparison with conventional markers.

【Expected Research Achievements and Scientific Significance】 Not only early detection of cancers but also drug

susceptibility and diagnosis which are difficult to be determined by conventional markers are expected to be enabled by this study. If the relationship between balance of immune system and homeostasis including changes of glycan structures is clarified, we might understand the mechanism of diseases deeply from the view point of biogenic networks, i.e, systems biology, which will have an great impact in the field of basic biology and development of medicines focusing on the significance of post-translational modification.

【Publications Relevant to the Project】・ Nishimura, S.-I., et al., “High-Throughput

Protein Glycomics: Combined Use of Chemoselective Glycoblotting and MALDI-TOF/TOF Mass Spectrometry” Angew. Chem. Int. Ed. 44, 91-96 (2005)

・Kamiyama, T., et al., “Identification of novel serum biomarkers of hepatocellular carcinoma using glycomic analysis” Hepatology 57, 2314-2325 (2013)




Information】 http://altair.sci.hokudai.ac.jp/g4/index.html

Figure1. Exploration of glycan biomarkers utilized by automated system for large scale glycomics


Title of Project： Design, Synthesis and Biological Application of in vivo Imaging Probes

Kazuya Kikuchi ( Osaka University, Graduate School of Engineering, Professor )

Research Area： Chemical Biology Keyword： Molecular Imaging, in vivo Imaging

【Purpose and Background of the Research】 One of the great challenges in the post-genome era

is to clarify the biological significance of intracellular molecules directly in living systems. If we can visualize a molecule in action, it is possible to acquire biological information, which is unavailable if we deal with cell homogenates. One possible approach is to design and synthesize chemical probes that can convert biological information to chemical output. In this research, in vivo imaging probe will be developed.

【Research Methods】 Real-time imaging of enzyme activities in vivo

offers valuable information in understanding living systems and in the possibility to develop medicine to treat various forms of diseases. Magnetic resonance imaging (MRI) is an imaging modality adequate for in vivo studies. Because background signal is hardly detectable, 19F-MRI probes are promising for in vivo imaging. A novel design strategy for 19F-MRI probes to detect protease activities is proposed. Using this probe as a positive contrast agent, the probe could detect enzyme activity spatially from an image using 19F MRI. I this current research, highly sensitive detection

should be possible by using nanoparticle with fluorine compound. Protein fluorescent labeling provides an

attractive approach to study the localization and function of proteins in living cells. Recently, a specific pair of a protein tag and its ligand has been utilized to visualize a protein of interest. The advantage of this protein labeling system is that a variety of fluorescent molecules are potentially available as labeling reagents, and that the protein tag is conditionally labeled with its fluorescent ligand. A protein tag (BL-tag), a mutant -lactamase, modified to be covalently bound to the designed labeling probes was developed. Multicolor labeling for intracellular protein will be developed.

【Expected Research Achievements and Scientific Significance】 Current limit of the application of chemical

probes on the molecular imaging is in vivo application. The successful application of the chemical probes in this research should prove the significance of interdisciplinary research in the imaging research.

【Publications Relevant to the Project】・S. Mizukami, R. Takikawa, F. Sugihara, Y. Hori, H.

Tochio, M. Wälchli, M. Shirakawa & K. Kikuchi, “Paramagnetic Relaxation-based 19F MRI Probe to Detect Protease Activity”, J. Am. Chem. Soc., 130, 794-795 (2008).

・S. Mizukami, S. Watanabe, Y. Akimoto & K. Kikuchi, “No-Wash Protein Labeling with Designed Fluorogenic Probes and Application to Real-Time Pulse-Chase Analysis”, J. Am. Chem. Soc., 134, 1623-1629 (2012).




Information】 http://www-molpro.mls.eng.osaka-u.ac.jp/English/indexeng/indexENG.html [email protected]

Fluorescence Imaging

MR Imaging

Imaging Probes

－78－


Title of Project： Exploration of Novel Markers on Cancer and Development of a Technology for the Diagnosis Utilized by Comprehensive Glycomics

Shin-Ichiro Nishimura ( Hokkaido University, Faculty of Advanced Life Science, Professor )

Research Area： Complex systems Keyword： Searching diagnosis chemicals

【Purpose and Background of the Research】 Serum biomarkers are important to detect

diseases in early stage and useful for decision of treatment easily and quickly. In this study we will focus on gastrointestinal cancers including hepatocellular carcinoma, pancreatic cancer and colon cancer, and urological cancers including renal cell carcinoma and prostate cancer, to explore highly sensitive- and disease/pathologically specific- biomarkers by means of novel, large scale and comprehensive glycomics approach. We have developed automated system for pre-treatment and glycoblotting, ‘‘Sweetblot” (Japan Science and Technology Agency JST, 2003-2011). Utilized by the system, we will construct a highly reliable database of patients’ glycans, which allows us to explore glycobiomarkers with clinical information provided from longitudinal/cross-sectional studies. It is believed to enable us to achieve practical study for clinical applications.

【Research Methods】 “SweetBlot” is an automated system, which

utilizes glycoblotting method (Angew. Chem. Int. Ed. 2005, 44, 91-96), allowing us to enrich glycans specifically from crude mixtures from biological materials, such as serum. Once we set 10 L of serum onto 96-well micro plate, extraction, modification, label with tag, spot onto a target plate and analysis by MALDI-TOF/MS will be perfoemed automatically. Glycan profiles from 96 patients will be obtained in almost a day.

Here we will apply 200-300 samples from patients in each region of disease, including serum, urine, tissues and cultured cells, to “Sweetblot”. We will analyze the samples which are sequentially obtained from the same individuals, and also from the same disease patients in the distinct hospitals. Potential glycan biomarkers will be found from the accumulated glycan data, which will provide us the efficiency of medicines and/or prognosis, following to an evaluation by comparison with conventional markers.

【Expected Research Achievements and Scientific Significance】 Not only early detection of cancers but also drug

susceptibility and diagnosis which are difficult to be determined by conventional markers are expected to be enabled by this study. If the relationship between balance of immune system and homeostasis including changes of glycan structures is clarified, we might understand the mechanism of diseases deeply from the view point of biogenic networks, i.e, systems biology, which will have an great impact in the field of basic biology and development of medicines focusing on the significance of post-translational modification.

【Publications Relevant to the Project】・ Nishimura, S.-I., et al., “High-Throughput

Protein Glycomics: Combined Use of Chemoselective Glycoblotting and MALDI-TOF/TOF Mass Spectrometry” Angew. Chem. Int. Ed. 44, 91-96 (2005)

・Kamiyama, T., et al., “Identification of novel serum biomarkers of hepatocellular carcinoma using glycomic analysis” Hepatology 57, 2314-2325 (2013)




Information】 http://altair.sci.hokudai.ac.jp/g4/index.html

Figure1. Exploration of glycan biomarkers utilized by automated system for large scale glycomics


Title of Project： Design, Synthesis and Biological Application of in vivo Imaging Probes

Kazuya Kikuchi ( Osaka University, Graduate School of Engineering, Professor )

Research Area： Chemical Biology Keyword： Molecular Imaging, in vivo Imaging

【Purpose and Background of the Research】 One of the great challenges in the post-genome era

is to clarify the biological significance of intracellular molecules directly in living systems. If we can visualize a molecule in action, it is possible to acquire biological information, which is unavailable if we deal with cell homogenates. One possible approach is to design and synthesize chemical probes that can convert biological information to chemical output. In this research, in vivo imaging probe will be developed.

【Research Methods】 Real-time imaging of enzyme activities in vivo

offers valuable information in understanding living systems and in the possibility to develop medicine to treat various forms of diseases. Magnetic resonance imaging (MRI) is an imaging modality adequate for in vivo studies. Because background signal is hardly detectable, 19F-MRI probes are promising for in vivo imaging. A novel design strategy for 19F-MRI probes to detect protease activities is proposed. Using this probe as a positive contrast agent, the probe could detect enzyme activity spatially from an image using 19F MRI. I this current research, highly sensitive detection

should be possible by using nanoparticle with fluorine compound. Protein fluorescent labeling provides an

attractive approach to study the localization and function of proteins in living cells. Recently, a specific pair of a protein tag and its ligand has been utilized to visualize a protein of interest. The advantage of this protein labeling system is that a variety of fluorescent molecules are potentially available as labeling reagents, and that the protein tag is conditionally labeled with its fluorescent ligand. A protein tag (BL-tag), a mutant -lactamase, modified to be covalently bound to the designed labeling probes was developed. Multicolor labeling for intracellular protein will be developed.

【Expected Research Achievements and Scientific Significance】 Current limit of the application of chemical

probes on the molecular imaging is in vivo application. The successful application of the chemical probes in this research should prove the significance of interdisciplinary research in the imaging research.

【Publications Relevant to the Project】・S. Mizukami, R. Takikawa, F. Sugihara, Y. Hori, H.

Tochio, M. Wälchli, M. Shirakawa & K. Kikuchi, “Paramagnetic Relaxation-based 19F MRI Probe to Detect Protease Activity”, J. Am. Chem. Soc., 130, 794-795 (2008).

・S. Mizukami, S. Watanabe, Y. Akimoto & K. Kikuchi, “No-Wash Protein Labeling with Designed Fluorogenic Probes and Application to Real-Time Pulse-Chase Analysis”, J. Am. Chem. Soc., 134, 1623-1629 (2012).




Information】 http://www-molpro.mls.eng.osaka-u.ac.jp/English/indexeng/indexENG.html [email protected]

Fluorescence Imaging

MR Imaging

Imaging Probes

－79－


Research (S)

Documents

Grant-in-Aid for Scientific Research(S) Integrated Disciplines … · 2018-12-10 · Markov Bases in Algebraic Statistics. Springer Series in Statistics, Vol. 199. Springer. 2012