ACADEMIA SINICA
Add: 128 Academia Rd., Sec.2, Nankang, Taipei 11529, Taiwan, R.O.C. Tel: 886-2-2782-2120 Fax: 886-2-2785-3847 http://www.sinica.edu.tw
Significant Research Achievements of Academia Sinica
ACADEMIA SINICA
2012
Significant Research Achievements of
ACADEMIA SINICA
2012
2012
ACADEMIA SINICA
Significant Research Achievements of Academia Sinica
President of Academia Sinica
Academia Sinica has the mission to conduct cutting-edge research in the humanities and sciences, nurture academic talents, and issue policy advisories to become the most eminent research institution in Taiwan. It encompasses 24 research institutes and 7 research centers, which are organized into three divisions: Mathematics and Physical Sciences, Life Sciences, and Humanities and Social Sciences. The past year has witnessed a continuous and fruitful growth for Academia Sinica. More than four thousand and two hundred highquality publications (an average of 5.0 publications per researcher) in forms of journal articles, proceedings papers, and books are not just evident results for the endeavors and talents of our research fellows but also a symbol of passion and enthusiasm for the pursuit of better understanding of nature and sciences. Consistent and measurable progress has not only made Academia Sinica the leading research institution nationwide but also a formidable opponent to its neighboring universities in other countries. In 2012, its number of papers listed in SCI, SSCI, and A&HCI has reached 2,294, an average of 2.68 per research. Besides, according ISI Essential Sciences Indicators (ESI), Academia Sinca has an average of 11.60 citations per paper in the last decade, which exceeds National Taiwan University’s 9.48, Chinese Academy of Sciences’ 9.22, and Peking University’s 9.64. Furthermore, according to the recent analysis in ESI, Academia Sinica was ranked among the top 1% of research institutions in 15 fields for the number of times papers have been cited. Finally, the number of highly cited papers increased remarkably year by year and the influence of publication published by Academia Sinica was noteworthy in the world. Significant Research Achievements is Academia Sinica’s annual publication, which shares its research results with the public. 77 papers and book are selected this year, covering various scientific fields. In humanities and
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A Message from the President Pursuing Excellence
social sciences, we include topics raging from Chinese inscriptions, the relationship between modern history and social changes, and aesthetic features of Chinese poetry. In mathematics and physical sciences, this issue features a study of iron-based superconductivity, developing high-potential compound for using in the next generation electronic devices, and the application of multimedia. In life sciences, important topics in the studies of the causes of human diseases, the mechanism of evolution, and new drug design. Aside from publications, Academia Sinica shows progress too in its endeavors to promote closer international academic exchange. The international cooperation projects introduced in this issue are jointly executed by research institutions from all over the world. Through Academia Sinica’s enthusiastic participations in such collaborative projects, Taiwan has proved itself capable of playing an important role in the advancement of science. On the other hand, we are also glad to see the achievements made by our Taiwan International Graduate Program (TIGP). TIGP has now students coming from 37 countries. Most graduates continue to pursue research at internationally renowned research institutions and bio-technology companies. Others, who join companies in other areas of industry, also show excellent performance in their chosen fields. By assuring the protection of intellectual property rights, encouraging patent applications, increasing technology transfer, and holding joint conferences on research achievements with other domestic research institutions, Academia Sinica hopes to strengthen the cooperation between research and industry and assist the government in developing emerging industries. Innovation is the key to the continuous growth in Taiwan’s knowledge-based economy. With emerging basic research as a solid foundation, further economic development can be established through technology transfer. At present, crucial areas awaiting further study include translational medicine, biomass and solar energy, issues concerning environmental changes and global warming, gene transformation and stem cell research, knowledge economy and cultural industry studies. Academia Sinica will continue to explore these areas and endeavor to promote Taiwan’s economy and the well-being of the people.
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CONTENTS 2
A Message from the President
6
Introduction of Academia Sinica
8
Research Achievements
16
2012 Significant Research Achievements of Academia Sinica
Division of Mathematics and Physical Sciences
18
Anisotropic Energy Gaps of Iron-based Superconductivity from Intra-band Quasiparticle Interference in LiFeAs Milan P. Allan, Andreas W. Rost, Andy P. Mackenzie, Yang Xie, J. C. Séamus Davis, Kunihiro Kihou, Chul-Ho Lee, Akira Iyo, Hiroshi Eisaki, and Tien-Ming Chuang
20
The Synthesis, Crystal Structure and Charge-transport Properties of Hexacene Motonori Watanabe, Yuan-Jay Chang, Shun-Wei Liu, Ting-Han Chao, Kenta Goto, Md. Minarul Islam, Chih-Hsien Yuan, Yu-Tai Tao, Teruo Shinmyozu, and Tahsin J. Chow
22
The Primitive Nature of Large Low Shear-wave Velocity Provinces
24
Revealing the Stereo-specific Chemistry of the Reaction of Cl with Aligned CHD3(v 1=1)
26
The Acoustic Emotion Gaussians Model for Emotion-based Music Annotation and Retrieval
Frédéric Deschamps, Laura Cobden, and Paul J. Tackley
Fengyan Wang, Kopin Liu, and T. Peter Rakitzis
Ju-Chiang Wang, Yi-Hsuan Yang, Hsin-Min Wang, and Shyh-Kang Jeng
Division of Life Sciences
28
Distinct Phytochrome Actions in Non-vascular Plants Revealed by Targeted Inactivation of Phytobilin Biosynthesis Yu-Rong Chen, Yi-Shin Su, and Shih-Long Tu
30
BMP and Delta/Notch Signaling Control the Development of Amphioxus Epidermal Sensory Neurons: Insights into the Evolution of the Peripheral Sensory System Tsai-Ming Lu, Yi-Jyun Luo, and Jr-Kai Yu
4
32
Changing Trends in the Prevalence of Common Mental Disorders in Taiwan: A 20-year Repeated Cross-sectional Survey Tiffany S.-T Fu, C.-S Lee, David Gunnell, W.-C Lee, and Andrew T.-A Cheng
34
The Evolution of Low Mutation Rates in Experimental Mutator Populations of
Saccharomyces cerevisiae
Michael J. McDonald, Yu-Ying Hsieh, Yen-Hsin Yu, Shang-Lin Chang, and Jun-Yi Leu
36
Crystal Structure of Staphylococcus aureus Transglycosylase in Complex with a Lipid II Analog and Elucidation of Peptidoglycan Synthesis Mechanism Chia-Ying Huang, Hao-Wei Shih, Li-Ying Lin, Yi-Wen Tien, Ting-Jen Rachel Cheng, Wei-Chieh Cheng, Chi-Huey Wong, and Che Ma
Division of the Humanities and Social Sciences
38
Jiagu Wenzi Bian (Understanding the Oracle Bone Inscriptions)
40
Qian Qianyi “Bingta xiaohan zayong” Lunxi (A Study of Qian Qianyi’s “ Forty-six Miscellaneous Poems to Dispel Cold on My Sickbed” )
Zong-Kun Li
Lawrence C. H. Yim
42
After Empire: The Conceptual Transformation of the Chinese State, 1885-1924
44
WTO and the Greater China: Economic Integration and Dispute Resolution
46
The Psychological Well-being of East Asian Youth
48
2012 Abstracts of Other Significant Publications
Peter Zarrow
Chien-Huei Wu
Chin-Chun Yi
5
Introduction of Academia Sinica Academia Sinica, founded in 1928, is the most preeminent academic institution in Taiwan with a mission to pursue research excellence, nurture academic talents, and issue policy advisories. President Dr. Chi-Huey Wong, assisted by Vice Presidents, Fan-Sen Wang, Chien-Jen Chen and Shie-Ming Peng, has taken the leadership to make further progress in improving research conditions and results. Academia Sinica currently has 24 institutes and 7 research centers under three divisions: the Division of Mathematics and Physical Sciences, the Division of Life Sciences, and the Division of Humanities and Social Sciences. At present, there are more than 2,000 researchers with Ph.D. degree. Among 264 academicians, there are 8 Nobel laureates. Central Office of Administration and Central Academic Advisory Committee were later established to facilitate the general administration and the promotion of academic development. The purpose of academic research is to improve human life. Academia Sinica will continue its tradition of pursuing solid research while exploring new knowledge and will remain focused on the needs of society in the hope of enriching human civilization.
》Organization Council of Academia Sinica
Central Office of Administration
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President
Convocation of Academicians
Vice Presidents
Central Academic Advisory Committee
General Assembly
Academic Advisory Committees for the Institutes and Research Centers Institutes and Research Centers
》Institutes and Research Centers Division of Mathematics and Physical Sciences Institute of Mathematics Institute of Physics Institute of Chemistry Institute of Earth Sciences Institute of Information Science Institute of Statistical Science
Institute of Atomic and Molecular Sciences Institute of Astronomy and Astrophysics Research Center for Applied Sciences Research Center for Environmental Changes Research Center for Information Technology Innovation
Division of Life Sciences
Institute of Plant and Microbial Biology Institute of Cellular and Organismic Biology Institute of Biological Chemistry Institute of Biomedical Sciences
Institute of Molecular Biology Agricultural Biotechnology Research Center Genomics Research Center Biodiversity Research Center
Division of the Humanities and Social Sciences Institute of History and Philology Institute of Ethnology Institute of Modern History Institute of Economics Institute of European and American Studies Institute of Sociology Institute of Chinese Literature and Philosophy Institute of Taiwan History Institute of Linguistics Institute of Political Science Institutum Iurisprudentiae Research Center for Humanities and Social Sciences
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Research Achievements Faculty members at Academia Sinica have devoted themselves to their research with an aim to open up new areas of intellectual endeavor. Striving to excel in the intense scientific race in R&D across the world, Academia Sinica constantly reviews its academia competitiveness and evaluates its future development strategies. To increase its international visibility, Academia Sinica has taken initiatives in enforcing internationalization, academic collaborations, and the recruitment of talents. Throughout the years, Academia Sinica and its research faculty have gained much recognition from the international community. Nevertheless, our ultimate concern remains enhancing the integral value of the community as a whole. Through the applications of research results and technology transfer, Academia Sinica seeks to contribute back to the society and increase the well beings of people in Taiwan.
Analysis of Published Papers
Academia Sinica endeavors to achieve excellence in research. The number and quality of its paper have increased rapidly. In 2012, there were 2,294 papers in Web of Science (WOS), 1,301 more than in 2002 (993). The average of number of papers by researchers in 2012 was 2.68, higher than 1.39 in 2002. Besides, in view of the graph of the number of highly cited papers by Academia Sinica, the number of cited papers has increased progressively for the past eleven years, and kept advancing in the coming future.
Academia Sinica Ranked among Top 1% of Research Institutions in 15 Fields, 2002-2012
According to the analysis of Thomson Reuter’s Essential Science Indicators (ESI), Academia Sinica was ranked among the top 1% of research institutions in 15 fields in the past 11-years period. In comparison with the 20012011 ESI data, two fields (viz. Pharmacology & Toxicology and Social Sciences, General) of which are newly added. In addition, ESI also witnesses the strong influence of our publications in Material Sciences and Microbiology, and the average number of citations per paper of which is 15.23 and 16.21 respectively, higher than that of most universities and research institutions in Asia.
38,429
11.86
Chemistry
31,952
12.41
Clinical Medicine
17,588
14.45
Biology & Biochemistry
17,088
13.21
Molecular Biology & Genetics
13,826
18.10
Plant & Animal Science
12,590
11.44
Geoscience
9,207
10.36
Material Science
8,801
15.23
Microbiology
4,127
16.21
Engineering
3,815
5.56
Pharmacology & Toxicology (NEW)
2,753
12.24
Environmental / Ecology
2,258
9.18
Computer Science
1,940
3.84
Agricultural Science
1,350
8.60
643
2.67
No. of Papers
600 400 200
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
2.05
1,500
1.50
1,000
1.00
500
0.50
0 2002
3.00
0.00 2002 2003
2004
2005 2006
2007 2008 2009
2010
2011 2012
論文數/研究人員
論文數
論文數
800
2,000
論文數 No. of Papers 平均每位研究人員WOS論文數 Average Papers Published per Researcher
Average Papers Published Per Researcher
2,500
Top 1% Papers 排名前 1%論文數 Top 10% Papers 排名前10%論文數 排名前20%論文數 Top 20% Papers
1000
No. of Papers
Physics
Academia Sinica Number of Papers Published & Average Papers Published by each Researcher, 2002-2012
1200
8
Citations Per Paper
Social Sciences, General (NEW)
Academia Sinica Number of Highly Cited Papers, 2002-2012
0
Citations
Field
Intellectual Property Management and Technology Transfer Academia Sinica attempts to benefit society through its outstanding research achievements. The Office of Public Affairs is responsible for protecting and managing Academia Sinica’s intellectual property rights, encouraging the disclosure of new discoveries, developing partnerships and collaborations with private sectors, and promoting technology transfer. In 2012, Academia Sinica filed 98 patent applications, was granted 72 patents, and signed 90 licenses as well as 12 cooperative research and development agreements (CRADA). By technology transfer, Academia Sinica has assisted the establishment of start-up companies and provided them with crucial support for the commercialization and development of research outcomes of Academia Sinica with the goal improving the development of Taiwan’s industry and its international competitiveness.
Academia Sinica Patents and Revenue-based License
License Agreements Executed in 2012
180
Application of HLA-B Molecules for Drug Screen in Predicting Drug Hypersensitivity
140
Maltose Dehydration Crystallization Technology
●
Facile Synthesis of Grapheme
●
●
●
●
●
●
No. of Patents
●
160
120 100 80 60
Dynamic Backlight Scaling for Mobile Streaming Applications Music Recommendation Based on Listening Context Microwave Effect on Chemical or Enzymatic Hydrolysis of Glycosidic Bond
40 20 0
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
No.of Applications Filed
41
49
76
70
97
95
115
160
170
112
88
98
No.of Patents Issued
22
19
26
26
26
44
34
38
37
57
53
72
Fabricating 3D Culture Scaffolds by Microfluidics Localization System for Logistics Operation in Enterprise Resource Management Establishment of Ornamental Transgenic Fish Expressing Fluorescent Proteins by Musclespecific Promoter
2012
600
500
NT in Millions
●
Application of Cancer Cell-specific Peptide for Tumor Targeted Drug Delivery
400
300
200
100
Intellectual Property Rights and Technology Transfer in 2012 Patent Applications Filed
98
Patent Issued
72 (27)*
License Executed
90
Licensing Revenue (NT$ in Millions) 83 Licensing Deal (NT$ in Millions)
42
Royalties (NT$ in Millions)
7.46
CRADA Executed
12
CRADA Grant (NT$ in Millions)
14.09
0
License Deal (NT in Millions)
License Income (NT in Millions)
24
10
19
23
5
18
312
324
494
272
289
83
17
9
11
11
5
0.6
17
13
18
11
62
42
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
0.02
0.04
1.10
1.28
0.60
0.27
0.19
2.98
4.32
5.50
9.29
7.46
9.00 8.00 7.00 6.00 5.00 4.00 3.00 2.00 1.00 0.00
( )* Cases of US patents
2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012
10.00
NT in Millions
●
Royalty (NT in Millions)
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Awards and Honors
The academic competitiveness of Academia Sinica is best demonstrated by the number of prestigious awards and honors bestowed upon its researchers. In 2012, many researchers have been recognized internationally for their exceptional accomplishments, for instance, Yuan-Tseh Lee was bestowed Order of Manuel Amador Guerrero by Republic of Panama and Ordre National du Merite by France. Many researchers have also been recognized for their accomplishment through domestic awards and honors, for example, Hsiang-Nan Li and Shang-Cheng Hung were awarded the Academic Award by the Ministry of Education. In the past 5 years, many researchers won National Science Council awards: 45 researchers received the Outstanding Research Award, 10 researchers received the Merit Research Fellow Award, and 18 researchers received the Ta-You Wu Memorial Award.
List of Awards and Honors Bestowed on Academia Sinica Researchers in 2012 International Academia Sinica Researchers
Awards and Honors
Order of Manuel Amador Guerrero, Republic of Panama
Academia Sinica President Emeritus Yuan-Tseh Lee has been awarded the "Order of Manuel Amador Guerrero" by the Government of the Republic of Panama for playing a leading role in the advancement of science for educational and peaceful purposes.
Antonio Zampolli Prize, European Language Resources Association (ELRA)
Chiu-Yu Tseng
AAAS Fellow
Wolfgang Schmidt
Order of Manuel Amador Guerrero, Republic of Panama
Yuan-Tseh Lee
TWAS Membership
Kuan Wang
TWAS Young Affiliate
Tzu-Ching Chang
Arthur C. Cope Award
Chi-Huey Wong
Member, Global Young Academy
Shang-Te Danny Hsu
Paju Book Award
Fan-Sen Wang
Nikkei Asia Prize
Chi-Huey Wong
Academy Gold Medal of Honor Award, Academy of Transdisplinary Learning and Advanced Studies
Ovid J.-L. Tzeng
Member, National Academy of Engineering
Chao-Han Liu
Ordre National du Merite, France
Yuan-Tseh Lee
Domestic
Awards and Honors
Ministry of Education 16th National Professorships and 56th Academic Awards
Hsiang-Nan Li and Shang-Cheng Hung received the Ministry of Education 56th Academic Awards in recognition of their research of perturbative quantum chromodynamics and glycobiology respectively.
Scholarly Monograph Award in the Humanities and Social Sciences, Academia Sinica 5 scholars were announced the first recipients of the Academia Sinica Scholarly Monograph Award in the Humanities and Social Sciences. The winning monographs cover research in art, literature, history and anthropology.
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Academia Sinica Researchers
Senior Fullbright Research Grant
Kuo-Chang Huang, Yu-Yueh Tsai
Taiwan Outstanding Women in Science, Wu Chien-Shiung Scholarship Foundation
Bon-Chu Chung, Chao-Wen Wang
Harvard-Yenching Visiting Scholar Program
Min-Hsiung Huang
Academic Award, Ministry of Education
Hsiang-Nan Li, Shang-Cheng Hung
Award for Junior Research Investigators, Academia Sinica
Jer-Lai Kuo, Chau-Hwang Lee, Chao-Wen Wang, Chung-Yi Wu
First Class Personnel Professional Medal, Ministry of Civil Service, Directorate-General of Personnel Administration
Ovid J.-L. Tzeng
Academician, Academia Sinica
Shaw-Chen Liu, Ker-Chau Li, Fu-Tong Liu, Soo-Chen Cheng, Tao-Shih Hsieh, Su-May Yu, Ming-Daw Tsai, Shou-Chien Shih, Yun-Han Chu
Medals of Recognition for Professional Educational and Cultural Contributions, Ministry of Education
Ovid J.-L. Tzeng
Y. Z. Hsu Scientific Paper Award
Ming-Yu Lai
Outstanding Medical and Pharmaceutical Science and Technology Award, Tien-Te Lee Foundation
Shang-Cheng Hung
Exploration Research Award, Pan Wen Yuan Foundation
Kate Ching-Ju Lin
Lecture in Honor of Former President Hu Shih, Academia Sinica
Chien-Liang Lee
Scholarly Monograph Award in the Humanities and Social Sciences, Academia Sinica
Shou-Chien Shih, Peter Zarrow, Siao-Chen Hu, Shao-Hua Liu
Ta-You Wu Memorial Award, National Science Council
Ya-Ju Hsu
Merit Research Fellow Award, National Science Council
Jen-Leih Wu, Yu-Chan Chao
Outstanding Research Award, National Science Council
Shao-Hua Liu, Shu-Hsing Wu, Hsiang-Nan Li, Yi-Ling Lin, Shang-Cheng Hung, Yu-Ju Chen, Ming-Syan Chen
International Academic Exchange and Cooperation Academia Sinica has been expanding rapidly in international academic exchange and cooperation, since the collaborations with more than 334 academic research institutions and universities in more than 40 countries. Academia Sinica proceeded further by signing cooperation agreements with College of Chemistry, University of California, Berkeley; University of California, San Diego; The Scripps Research Institute; The California Institute of Biomedical Research, USA; Hebrew University of Jerusalem; and Memoranda of Understanding with Ecole Normale Superieure de Lyon, France; University of Malaya; National University of Singapore. Other than that, Academia Sinica and National Science Council jointly endorsed the international collaboration agreement with The European Molecular Biology Organization (EMBO) and The European Molecular Biology Conference (EMBC) on behalf of Taiwan hoping to foster talents in the field of Life Sciences. Internationally, as the member of International Council for Science (ICSU), Academia Sinica encourages and supports 37 domestic academic associations to join the member organizations under the ICSU, currently we are members of 56 international organizations. Academia Sinica and ICSU jointly established the Integrated Research on Disaster Risk International Centre of Excellence (IRDR ICoE) for the promotion of scientific education and research. In order to accelerate the collaborations, Academia Sinica also joined the InterAcademy Panel (IAP)-Global Network of Science Academies to work with other national academies on critical global issues. Academia Sinica also joined the International Human Rights Network, focusing on human rights issues. In 2009, President Wong inaugurated the Academia Sinica Lecture which invites distinguished scholars from all over the world to visit and share their expertise on a regular basis. For 2012, Dr. Ada E. Yonath, 2009 Nobel Laureate in Chemistry, delivered a lecture on “Is there a Limit to Life Expectancy? Wishes, Predictions and Reality”, and Dr. Eric S. Maskin, 2007 Nobel Laureate in Economy, delivered lectures on “Financial Crisis: Why do they Occur and what to do about them?” and “Election and Strategic Voting: Condorcet and Borda”. In 2012, Dr. Barbara H. Liskov, Dr. Richard Saller, Dr. Donald B. Dingwell, Dr. Peter. H. Raven, Dr. Gong Ping Yeh, Dr. Michael M. Crow, and Dr. Elizabeth Blackburn, were invited as speakers of the Special Lecture. Both Lectures enjoyed great popularity among the audience.
Foreign Employees at Academia Sinica Country (Region) No. of Persons
Malaysia
India
Japan
US
Europe
Mainland China
Korea
Hong Kong
Oceania
Others
48
69
40
44
56
24
7
7
1
36
There are in total more than 332 foreign employees at Academia Sinica, who are from more than 42 countries and regions. The ratio of researchers (incl. specialists) to contract-based employees, who work mainly as research supporting staff, is approximately 1:4.
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International Cooperation Project Taiwan-American Occultation Survey, TAOS & Trans-Neptunian Automated Occultation Survey, TAOS-2 The TAOS consists of four 0.5-meter optical telescopes located on Lulin Mountain in Taiwan. They automatically monitor 1,000 stars every clear night to search for Trans-Neptunian objects (TNOs) through stellar occultations. By studying the TNOs, we can better understand the early history of our solar system. The Academia Sinica Institute of Astronomy and Astrophysics (ASIAA) has also started the TAOS-2 project, to be sited in San Pedro de Martir Observatory in Mexico, to improve the sensitivity by 100 times. This will consist of three 1.3-meter telescopes which will be installed starting in 2013. TAOS is a stable and reliable facility on Lulin. We will continue to operate TAOS as training for students and for testing new equipment. Because of the remote observing capability of the TAOS telescopes and of its fast drive systems, TAOS has been successfully used to detect three optical afterglows of cosmic gamma ray burst events, typically within 1 minute of detection by space borne gamma ray observatories. In 2013, construction of TAOS-2 will be underway. The San Pedro de Martir site is being developed, with roads, civil infrastructures, power, and internet. We expect first light of TAOS-2 to be in 2013-2014.
A bird's-eye view of TAOS telescopes at Lulin Observatory
The Yuan Tseh Lee Array for Microwave Background Anisotropy, AMiBA
The AMiBA is a platform-mounted interferometer sited on Mauna Loa in Hawaii to measure the structure of the cosmic microwave background. It is the first major astronomical instrument led and built by Taiwan. It is designed, constructed, and operated by the ASIAA, in major collaboration with National Taiwan University. The initial 7-element interferometer was dedicated in October 2006 and science operations have started since then. An expansion to the 13-element configuration was completed in 2009. Scientific studies continue to image the dark matter distribution in distant clusters of galaxies via the Sunyaev-Zeldovich Effect. Since 2008, 20 papers have been published, and 4 more papers are in press or have been submitted. We are studying the potential of using the AMiBA for lower frequency imaging of distant red shifted galaxy clusters in carbon monoxide (CO). This is a stacking experiment in frequency space in order to detect large scale structures in the spatialredshift domain. Such Baryon Acoustical Oscillations have been successfully detected in HI and a similar detection in CO would be important for studying the formation of large scale molecular complexes in the early universe.
AMiBA is comprised of thirteen 1.2 m antennas and sited on Mauna Lao in Hawaii.
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AMiBA observatory was dedicated in 2006.
Submillimeter Very Long Baseline Inteferometer, submm VLBI S u b m m Ve r y L o n g B a s e l i n e I n t e r f e ro m e t r y (VLBI) will combine the Submillimeter Array (SMA) and Atacama Large Millimeter Array (ALMA) and add a third station in Greenland for intercontinental baselines. Collaborating with Smithsonian Astrophysical Observatory (SAO), the ASIAA was awarded the Atacama Large Millimeter Array-North America (ALMANA) prototype 12 m telescope in 2011 for redeployment as the Greenland Telescope. The scientific target is to prove directly the existence of black holes by imaging the shadow of a Super Massive Black Hole (SMBH) at the center of an Active Galactic Nucleus. After studies, we had identified the summit of the Greenland ice sheet as the best site for the third station. We are currently retrofitting the Greenland telescope so that it can perform well at the very low temperature of -60℃ in Greenland.
This is the VLBI radiometer located at freezing Greenland Summit Station. It has collected the weather information of a year of the station.
We will deploy the Greenland Telescope, after appropriate retrofitting and improvements, to the 3000 m summit of Greenland, for the purpose of millimeter (mm) and submillimeter (submm) wavelength VLBI. Only submm VLBI will have the required angular resolution in the coming decade to resolve the image of the shadow in the most favorable cases. Two possible SMBH targets, Sgr A* at the center of our Milky Way Galaxy, and the nucleus of M87 in the Virgo cluster of galaxies, are expected to reveal the black hole shadow. Although the main science driver is submm VLBI, the site conditions will be excellent for single-dish observations at submm and far-infrared wavelengths. This is the ALMA-NA prototype 12 m telescope. We will pursue wide field single dish astronomy at THz in order to maximize the scientific output from this instrument.
Optical and Infrared Instrumentation Program, OIR
To support follow-up observations of high-redshift clusters, the ASIAA negotiated for the observing time on international optical and infrared telescopes from 2003. Through participating in the development of the Wide Field Infrared Camera (WIRCam) on Canada-France-Hawaii Telescope (CFHT) and the HyperSuprime Cam (HSC) project on the Subaru Telescope, Taiwan has gained access to CFHT and the Subaru Telescope. The HSC is the largest optical camera to be built in astronomy. ASIAA continues to collaborate in the development of the next generation instruments on these telescopes, including the Prime Focus Spectrograph (PFS) on Subaru Telescope. The H S C is being commissioned in 2013. While HSC provides wide-field broad band imaging, the next step is to extend the HSC capabilities in terms of multi-object spectroscopy via the PFS. The ASIAA joined the PFS project in 2011. We will work on the metrology camera and the Prime Focus Instrument (PFI). The ASIAA is also playing a significant role in managing the PFS project by b e i n g p a r t o f t h e P r o j e c t Management team. The entire PFS with all 4 spectrometers will be ready by 2015-2017.
HyperSuprime Cam mounted at focus of 8.2 m Subaru Japanese national telescope on Mauna Kea in Hawaii.
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Carbohydrate-Based Design of HIV Vaccine
Academia Sinica has been committed to the improvement of the vaccine against AIDS with the cooperation of International AIDS Vaccine Initiative and The Scripps Research Institute since 2008. The best strategy to control the worldwide epidemic of AIDS, caused by the human immunodeficiency virus (HIV), is the development of an effective preventive vaccine. The major challenge nowadays is how to identify unique neutralizing epitopes on the HIV envelope which are capable of eliciting broadly neutralizing antibodies in order to break down the strong viral defense. Since the HIV envelope proteins are heavily glycosylated by the human glycosylation machinary, a glycan array platform for the analysis of neutralizing antibody specificity developed by the research team at Genomics Research Center will be used to identify the optimal mixed-glycans combinations for vaccine design. In addition, an approach using glycan engineering of envelope glycoproteins gp120 as a vaccine will also be applied.
Pan Asian Population Genomics Initiative
On the 15th of March 2011, Pan Asia SNP consortium (PASNP) participants held a HUGO working summit session for the next stage PASNP project (PASNP 2.0). The new project was set to collect and analyze Asian genomic data to understand the history of human migration, local adaptation, and genetic diversity among Asian populations. Pan Asian Personal Genomics Initiative (PAPGI) was suggested to mark the new aims, new sequencing technologies and the much larger sequence data to be generated. A research team from the Institute of Biomedical Sciences, Academia Sinica, who has contributed substantially to PASNP will continue to participate in PAPGI. Pan Asian data will be made publically available to the worldwide scientific community for further studies on human evolution and medical applications.
The UNESCO-EOLSS Project
The Encyclopedia of Life Support Systems (EOLSS) is the world’s largest publication project created under the auspices of the UNESCO. Envisioned as an archival reference source on the sustainability of life on Earth, since 1996, the EOLSS has mobilized over 8,000 reputable scholars from more than 100 countries to give an account of the research on great variety of subjects. The EOLSS can be regarded as something of an ‘encyclopedia of encyclopedias’, and is broadly influential throughout the world.
Source: UNESCO-EOLSS, 2012
Professor Der-Chin Horng, a Research Fellow of the Institute of European and American Studies, Academia Sinica, was invited by the UNESCO to join the EOLSS in August 2010. His research on “International Law on Biotechnology” was published following formal peer-review in 2012. With this publication, Professor Horng has contributed to both the UNESCO and the sum of human knowledge. Research Institutes
Division of Mathematics and Physical Sciences
2012 International Cooperation Project Taiwan-American Occultation Survey, TAOS & Trans-Neptunian Automated Occultation Survey, TAOS-2
Construction for Seismic Morning and Tsunami Warning System and Promotion for Seismic Hazard Reduction within Taiwan and Philippine Region
Optical and Infrared Instrumentation Program, OIR
Dongsha Coral Growth Study
Submillimeter Very Long Baseline Inteferometer, submm VLBI
The Yuan Tseh Lee Array for Microwave Background Anisotropy, AMiBA
An International Study of Marine Biogeochemical Cycles of Trace Elements and their Isotopes
Division of Life Sciences
Division of the Humanities and Social Sciences
14
Carbohydrate-Based Design of HIV Vaccine
Studies of High-efficiency Tandem White Organic Light-emitting Diode Materials and Device Interfaces.
Pan Asian Personal Genomics Initiative (PAPGI)
Empowering the Methane Economy
Breast Cancer Association Consortium
The Effects of Various Wavelength Light Emitting Diodes (LEDs) Fishing Light Attractor on Aggregating Fish Assemblages
United Nations Educational, Scientific and Cultural Organization: International Law on Biotechnology
Doctorate Program
Taiwan International Graduate Program (TIGP)
To keep up with the pace of today’s fast evolving scientific and technological world and to promote the internationalization of higher education in Taiwan, Academia Sinica established the TIGP in collaboration with key domestic research universities. In addition to the all-English teaching and research environment, state-of-the-art facilities and globally renowned faculty, the TIGP also provides its Ph.D. students with the following benefits:1) a non-taxable monthly stipend of NT$32,000 (~US$970) for up to 36 months; 2) free Chinese language courses at primary level; 3) a cozy and convenient on-campus student dormitory with fully furnished single study bedrooms at affordable rates. TIGP has taken a step forward to fulfill its main mission–promoting the internationalization of higher education in Taiwan. The followings are also features that may help TIGP students extend their learning: Exceptional scientists have been invited to address and share with the TIGP students their unique stories on achieving success in their academic career. TIGP Student Travel Grant has been provided to encourage students to participate in important international conferences. The travel grant is intended to offer students the opportunities to meet and learn from experts in their related fields. Academia Sinica has substantial connections with distinguished overseas research universities and institutions providing TIGP students with great opportunities to visit and conduct research work in renowned laboratories/institutes. In order to attract more young and talented scholars to apply for the TIGP Ph.D. program, the TIGP International Internship Program (TIGP-IIP) was launched in 2010. It is an intensive pre-doctoral research training program that prepares its participating interns with the necessary knowledge and skills for future research or career development through rigorous hands-on training.
Degree Program (DP) M o re re c e n t l y, i n 2 0 0 8 , A c a d e m i a Sinica established the DP to provide a more advanced higher education environment for domestic students. Similar in design to the TIGP, the DP is also co-established with domestic universities. Currently the DP offers 7 interdisciplinary Ph.D. programs.
TIGP and Partner Universities Programs
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Partner Universities
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National Taiwan University http://www.ntu.edu.tw
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National Tsing Hua University http://www.nthu.edu.tw
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National Central University http://www.ncu.edu.tw/index.php
Department of Physics
Molecular and Biological Agricultural Sciences http://abrc.sinica.edu.tw/mbas/
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National Yang-Ming University http://www.ym.edu.tw
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National Tsing Hua University http://www.nthu.edu.tw National Chiao Tung University http://www.nctu.edu.tw
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National Tsing Hua University http://www.nthu.edu.tw
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Partner Universities
Cancer Biology and Drug Discovery
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National Taiwan University Kaohsiung Medical University China Medical University Taipei Medical University National Yang-Ming University
http://www.ntu.edu.tw/ http://www.kmu.edu.tw/ http://www.cmu.edu.tw/ http://www.tmu.edu.tw/v3/main.php http://www.ym.edu.tw
Genome and Systems Biology
National Taiwan University
http://www.ntu.edu.tw/
Microbial Genetics and Genomics
National Chung Hsing University http://www.nchu.edu.tw/
Information and Network Systems
National Chiao Tung University
Multimedia Systems and Intelligent Computing
National Cheng Kung University http://web.ncku.edu.tw/bin/home.php
http://www.cmu.edu.tw/ http://www.tmu.edu.tw/
http://www.nctu.edu.tw
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In 2012, Academia Sinica had more than 4,200 scientific publications including journal articles, books and proceedings papers. Among them, 2,294 papers have been listed in SCI, SSCI and A&HCI, with an average of 2.68 papers per researcher. This current issue of research achievements highlights a selection of fifteen key papers published in the last twelve months, covering a wide range of topics presented by each of the following divisions: Mathematics and Physical Sciences, Life Sciences, and the Humanities and Social Sciences. The Division of Mathematics and Physical Sciences currently comprises of eight institutes and three research centers. Each researcher in the division has published an average of 4.3 papers listed in SCI, SSCI and A&HCI in 2012. The total number of journal articles, books, and proceedings papers amounts to around 1,800, with an average of 5.3 publications per researcher. Over the years, the researchers in the Division of Mathematics and Physical Sciences have been carrying out high-quality basic researches to discover new phenomena, comprehend them, and create new knowledge. Important results include demonstrating anisotropic energy gaps of iron-based superconductivity from intra-band quasiparticle interference in LiFeAs; exploring the synthesis, crystal structure, and charge-transport properties of hexacene; understanding the primitive nature of large low shear-wave velocity provinces; revealing the stereospecific chemistry of the reaction of Cl with aligned CHD3; and developing an acoustic emotion Gaussians model for emotion-based music annotation and retrieval, etc.
Academia Sinica
The Division of Life Sciences comprises five institutes and three research centers. In 2012, researchers in this division published an average of 3.9 papers listed in SCI, SSCI and A&HCI. The total number of journal articles, books and proceedings papers has amounted to around 900, with an average of 4.0 publications per researcher. The researches of the institutes/centers cover a broad range of life sciences from basic to translational studies; major accomplishments include light sensing and signaling in non-vascular plants; signaling control of the development of amphioxus epidermal sensory neurons; using experimental evolution approach to investigate the mechanisms of mutation reduction; structural studies of drug target enzymes; and epidemiologic and genomic studies which lead to a better understanding of important human diseases. The Division of the Humanities and Social Sciences is comprised of eleven institutes and one research center. In 2012, researchers in this division altogether produced over 1,400 publications including journal articles, books and proceedings papers. On average, each researcher had 4.2 publications. The researches of the members of the institutes and center cover a wide range of important issues in humanities and social sciences, including a complete collection of the oracle bone inscriptions; a hermeneutic study of poems of Qian Qianyi, one of the most renowned poets of the Qing Dynasty; an illustration of the conceptual transformation of the Chinese state after empire collapsed; a research of economic integration and dispute resolution among China, Taiwan, Hong Kong and Macau under the WTO; and an investigation of significant social mechanisms affecting different growth patterns and to delineate the interplay of family, school, peers and community in the developmental process of East Asian youth, etc.
ACADEMIA SINICA
2012 Significant Research Achievements of Academia Sinica
◆
Division of Mathematics and Physical Sciences
Anisotropic Energy Gaps of Iron-based Superconductivity from Intra-band Quasiparticle Interference in LiFeAs Milan P. Allan§1,2,3, Andreas W. Rost§2,3, Andy P. Mackenzie3, Yang Xie2, J. C. Séamus Davis*1,2,3,4, Kunihiro Kihou5,6, Chul-Ho Lee5,6, Akira Iyo5,6, Hiroshi Eisaki5,6, and Tien-Ming Chuang*1,2,7 Condensed Matter Physics & Materials Science Department, Brookhaven National Laboratory, USA Laboratory of Solid State Physics, Department of Physics, Cornell University, USA 3 SUPA, School of Physics and Astronomy, University of St Andrews, UK 4 Kavli Institute at Cornell for Nanoscale Science, Cornell University, USA 5 National Institute of Advanced Industrial Science and Technology, Japan 6 JST, Transformative Research-Project on Iron Pnictides (TRIP), Japan 7 Institute of Physics, Academia Sinica, Taiwan § These authors contributed equally to this work. 1 2
Abstract
If strong electron-electron interactions between neighboring Fe atoms mediate the Cooper pairing in iron-pnictide superconductors, then specific and distinct anisotropic superconducting energy gaps Δi (k ) should appear on the different electronic bands i. Here we introduce intra-band Bogoliubov quasiparticle scattering interference (QPI) techniques for determination of Δi (k ) in such materials, focusing on LiFeAs. We identify the three hole-like bands assigned previously as γ, α2 and α1, and we determine the anisotropy, magnitude and relative orientations of their Δi (k ). These measurements will advance quantitative theoretical analysis of the mechanism of cooper pairing in iron-based superconductivity.
Iron-based high temperature superconductors
(FeSC) have an intricate crystal structure (Fig.1A) and a unique collinear antiferromagnetic (AF) parent state. The corresponding band structure in momentum
space (k -space) contains five electron bands in the Brillouin zone; the hole-like α 1, α 2 and γ bands surround theΓpoint, and the electron-like β 1 and β 2
bands surrounding the M point as shown in Fig. 1B.
The superconductivity derives from a commensurateantiferromagnetic and orthorhombic "parent" state.
The highest superconducting transition temperatures occur when the magnetic and structural transitions are
suppressed towards zero temperature by chemical doping or external pressure. Theories describing FeSC
are usually quite complicated. Nevertheless, they typically predict that the superconducting energy gap
functions Δ i (k ) on different bands, i, are anisotropic
in k -space, with each band exhibiting a distinct
1B Schematic Fermi surface of an ironbased superconductor like LiFeAs in the tetragonal non-magnetic Brillouin zone (solid line). The“one Fe zone”is shown as a dashed line. The blue, yellow and red curves show the hole-like pockets, α1, α2 and γ, respectively, surrounding theΓpoint, while the green curves show electron pockets, β1 and β2 surrounding the M point.
have reported the Δi (k ) to be isotropic in the k x/k y plane.
Subsequently, however, nodeless anisotropic gaps
of gap minima and maxima relative to the Brillouin zone
spanning the range 2mV→4meV on the γ band and 5meV→6meV on the α 2 band aroundΓwere reported
However, the detail superconducting gap structures
pocket at M, an anisotropic 3meV→4.5meV gap is also
90°-rotational (C4) symmetry and a specific relationship
axes.
in FeSC remain an open question. Thermodynamic and
in LiFeAs by two ARPES groups. For the electron-like
described, but the reported k -space positions of gap
transport studies (which cannot reveal Δi (k )) provide
maxima/minima appear mutually inconsistent. High-
almost all k -space resolved photoemission spectroscopy
could help to accurately quantify these fundamental
good evidence for electronic anisotropy. By contrast,
(ARPES) studies of these materials, including LiFeAs,
18
1A Top view of crystal structure in the FeAs plane. Dashed lines represent the one-Fe unit cell that would exist if all As were coplanar, while the actual unit cell of dimension a0≈0.38 nm is shown using solid lines.
resolution determination of Δi (k ) using other techniques
characteristics of superconductivity.
Bogoliubov quasiparticle scattering interference (QPI) imaging is a
suitable technique for high-resolution determination of Δi (k ). The scattering
interference patterns can be visualized in real space using spectroscopic imaging scanning tunneling microscopy, in which the tip-sample differential
tunneling conductance dI /dV (r ,E )≡g (r ,E ) is measured as a function of
location r and electron energy E. At T=1.2K, we can reach the necessary
energy resolution of ≤350μeV to resolve Δ i (k ). We first identify three
bands, h3 , h2 and h1, in our QPI data as shown in Fig. 2A and Fig. 2B. The
measured QPI dispersion, |q (E )| of these bands in Fig. 2C shows them all
to be hole-like. A quantitative comparison of our QPI data to both ARPES and quantum oscillation measurements identifies these bands with those previously assigned as α1, α2 and γ by ARPES. The complexity of overlapping QPI signals makes it challenging to yield
the Δi (k ) from measured g (q ,E ) maps. Therefore, we developed a restricted analysis scheme that still allows the pertinent Δi (k ) information to be easily
extracted, which is based on measuring the maximum scattering intensity
in a |q |-E plane along a specific high-symmetry direction as shown in Fig.3A
and 3B. Such a plot of intensity maxima actually contains all the information on Δ i (k ) for that C 4-symmetric band, including magnitude and relative
orientation. Most importantly, each Δi (k ) is determined experimentally
from a combination of: (i) the measured normal-state band dispersions,
(ii) the symmetry of Brillouin zone, and (iii) the measured geometrical
characteristics of the scattering intensity g (q ,E ) in a specific |q |-E plane.
The resulting anisotropic superconducting gaps on bands h3, h2, and h1 of LiFeAs are displayed in Fig. 4
In summary, our spectroscopic measurements determine the
anisotropy, magnitude and relative orientations of Δi (k ) on three hole bands
in LiFeAs. The Δi (k ) reported in ARPES studies on the same compounds appear in excellent agreement with our observations for the γ and α2 bands. The growing confidence and concord in the structure of Δi (k ) for LiFeAs will
3A Extracted maximum scattering intensity trajectory from g (|q |,E ) for q || ΓΜ containing the information on Δ(k ) for h3. 3B Extracted maximum scattering intensity trajectory from g (|q |,E ) for q || ΓX containing the information on Δ(k ) for h2. Blue: Opening along q || ΓΜ on the h1 band.
advance the quantitative theoretical study of the Cooper pairing mechanism therein.
2A The g (q ,E =7.7meV) map. The high intensity closed contour is a consequence of scattering interference within a large hole-like band h3. 2B The g (q ,E =-6.6meV) map showing the high intensity closed contours resulting from scattering interference from a smaller hole-like band h2, and h1 (inset). These data are measured at T =1.2K. 2C The measured energy dependence of the q (E )=2k (E ) for all three bands in normal state h1 (blue line), h2 (yellow) and h3 (red) along the marked directions. Both h3 and h2 are measured in the superconducting phase at T =1.2K. The h1 band is measured in the normal state (grey dots) T =16K showing how its maximum is very close to E F. Black dots: Remaining QPI signatures upon cooling into the superconducting phase.
4 Anisotropic energy gap structure Δi measured using QPI at T =1.2K on the three hole-like bands h3, h2 and h1 (Fig. 2C). These bands have been labeled γ, α 1 and α 2 before. Here, the 0.35 meV error bars stem from the thermal resolution at 1.2K.
▍Publication Science 336
(2012): 563-567.
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Division of Mathematics and Physical Sciences
The Synthesis, Crystal Structure and Chargetransport Properties of Hexacene Motonori Watanabe1, Yuan-Jay Chang1, Shun-Wei Liu2, Ting-Han Chao3, Kenta Goto4, Md. Minarul Islam1, Chih-Hsien Yuan1, Yu-Tai Tao1, Teruo Shinmyozu4, and Tahsin J. Chow1 Institute of Chemistry, Academia Sinica, Taiwan Ming Chi University of Technology, Taiwan 3 National Taiwan Normal University, Taiwan 4 Kyushu University, Japan 1 2
Abstract
Acenes can be regarded as one dimensional graphene, and exhibit a high potential for using in the next generation electronic devices. However, acenes larger than pentacene have been considered to be unstable and difficult to work with. In this work we showed that by using a physical vapor transport method, platelet-shaped crystals of hexacene can be prepared from a monoketone precursor. They are stable in the dark for a long period of time under an ambient condition. An OFET device made with a single crystal of hexacene displayed the highest hole mobility 4.28 cm2 V-1 s-1 with an on/off ratio of 1×105 and a threshold voltage of 37 V. These devices can function under an ambient environment for more than 19 days.
Acenes are a class of aromatic hydrocarbons
responsible for the high stability of hexacene in the
narrow HOMO–LUMO bandgap, which leads to a higher
in an edge-to-face manner, therefore not suitable for
most attractive features of acenes is their exceptionally conductivity than other organic materials.
Although larger acenes have great potential in a
wide range of applications, their utility is limited severely by both their low solubility and low stability in solutions.
Hexacene, for example, was reported more than 70 years
ago, yet its property has never been unambiguously described until recently. In this report, we developed a highly efficient solid-state synthesis of hexacene. The
solid state. In the crystal, the molecules are stacked dimerization. It is known that the electronic property
of acenes depends heavily on their molecular packing patterns. Based on the crystal data, a theoretical study
indicated that hexacene should possess a much smaller reorganization energy, a higher electronic coupling
parameter, and a substantially higher hole mobility than pentacene.
Field-effect trnasistors were fabricated using the
method involves thermal degradation of a monoketone
single crystals of hexacene. The crystals were grown on
conducted in the dark to minimize the possibility of self-
assembled monolayer of octyltrichlorosilane and placed
precursor to avoid side reactions. The reaction was
dimerization. Platelet single crystals were obtained by
physical vapour-transport (PVT) method. The precursor was heated at 180ºC in a nitrogen atmosphere to give a sizable amount of pure hexacene. It was then transferred
into a glass tube for PVT, and the tube was heated in an
a SiO2/silicon substrate, which was coated with a selfinside the PVT tube. After crystal growth, gold source
and drain electrodes were thermally deposited on top
of the substrate through a shadow mask. The OFET devices made with single crystals of hexacene displayed
the highest hole mobility of 4.28 cm2 V-2 s-2 with an on/
oven at 260-300ºC with a flow of argon gas. Blue-green
off ratio of 1×105 and a threshold voltage of 37 V. These
inside the glass tube. Pure hexacene thus prepared
for more than 19 days. The conductivity of solid-state
crystals were collected from a temperature gradient zone can be stored under ambient conditions in the dark for more than one month. X-ray diffraction analysis on single crystals revealed that hexacene molecules are
aligned in herringbone arrays, just like pentacene. It was observed that solid state hexacene is thermally stable up
to ~300ºC in the dark, but highly vulnerable in solutions under light.
20
The herringbone packing motif is believed to be
composed of linearly fused benzene rings. One of the
devices can function under an ambient environment
hexacene was estimated to be 2.21×10 -4 Sm -1. The
nature of pure hexacene was characterized successfully for the first time.
❶ (a) Physical appearances of the precursor 1 (left) and hexacene (right) in open air. (b) IR spectra of 1 (lower) and hexacene (upper). (c) TGA profile of 1. (d)
(top) CP-MAS spectra of 1; (middle) hexacene produced by heating 1 at 180 oC under an N2 atmosphere; (bottom) hexacene left at ambient condition in the dark for 30 days. Asterisks denote spinning sidebands.
❷ (a) Output characteristics. Inset shows a crystal with a scale bar of 50 μm. (b) Transfer characteristics recorded at V DS =-80V. (c) Time-dependent decay of performance. (d) Current (J ) vs. electric field (E ) plot of a hexacene crystal across gold electrodes at ambient condition.
▍Publication Nature Chemistry 4 (2012): 574-578.
21
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Division of Mathematics and Physical Sciences
The Primitive Nature of Large Low Shear-wave Velocity Provinces Frédéric Deschamps1, Laura Cobden2, and Paul J. Tackley3 Institute of Earth Sciences, Academia Sinica, Taiwan Institut für Geophysik, Universität Münster, Germany 3 Institute of Geophysics, Swiss Federal Institute of Technology Zurich, Switzerland 1 2
The lowermost (> 2400 km) Earth’s mantle mapped by seismic tomography is strongly heterogeneous, the most striking feature being two large regions where shear-wave velocity drops by a few percent
Abstract
compared to the averaged mantle. Additional seismic observations indicate that these structures, called
LLSVP cannot result from purely thermal effects. Compositional anomalies, whose exact nature is still debated, are required to fully explain seismic observations. Here, we show that LLSVP unlikely consist
of recycled oceanic crust (MORB). Unless they are heated up to unrealistic temperatures, high-pressure MORB would induce high shear-wave velocity, in contradiction with the observations. Instead, material enriched in iron by ~3.0% and in perovskite by ~20% compared to the regular mantle provides a good explanation for the LLSVP. Several additional geochemical and geodynamical arguments support a
primitive origin for this material. LLSVP may thus consist of reservoirs of primitive material that have differentiated early in the Earth’s history.
Seismic tomography images two large low shear-wave provinces (LLVSP) in the deep mantle. These structure are about 5000 km wide and are located beneath the Pacific and Africa. They were first interpreted as hot, buoyant superplumes, but several seismological observations, including the anti-correlation between bulk-sound and shear-wave velocity anomalies, invalidated this hypothesis. Interestingly, models of thermo-chemical convection have shown that deep reservoirs of chemically differentiated material can remain stable over periods comparable to the age of the Earth. Geophysical observations and geodynamic models ❶ Sensitivities of shear-wave velocity (left), bulk-sound velocity (middle), and density (right) to thus clearly indicate that LLVSP result the volume fraction of MORB as a function of depth. The color code indicates the cumulated likelihood around the median value. On each plot, the white dashed line indicates the median from the combination of thermal and value (i.e., 50% of the explored sensitivities lie on each side of this line), and the blue curves chemical heterogeneities. The nature of represent the 0.15 and 0.85 quartiles (i.e., 70% of the explored sensitivities lie within the area these chemical anomalies is however bounded by these curves). still debated, and two end-members set. A remarkable feature is that the sensitivities of hypotheses, the recycling of oceanic crust (MORB) both shear-wave (V S) and bulk-sound (V Φ) velocity to and the survival of reservoir(s) of primitive material, MORB are positive throughout the lower mantle (Figure are usually advocated. In this article, we calculated the 1). This observation has two important consequences. seismic signatures expected from these two hypothesis, First, to induce V S-anomalies around -2.0% (a typical and we show that LLSVP are more likely consisting in value for LLVSP), high-pressure MORB should be very material enriched in iron and perovskite (MgSiO3). hot, at least 1000 K hotter than the surrounding mantle. First we calculated sensitivities (i.e., partial V Second, derivatives) of seismic velocities to temperature, MORB, S and V Φ-anomalies should be correlated, in contradiction with seismic tomography. By contrast, the iron and perovskite using an appropriate equation of V sensitivity of state modeling and a coherent mineral physics data S to iron is strongly negative throughout
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the lower mantle, whereas the sensitivity of V Φ to perovskite is strongly positive. Material enriched in iron and in perovskite compared to the surrounding mantle is therefore likely to explain LLSVP, even for moderate temperature excess. We have then determined full distributions of seismic velocities and density anomalies by sampling the seismic sensitivities according to their own distributions, and used these distributions to calculate several statistical quantities, such as the likelihoods that V S- and V Φ-anomalies (dlnV S and dlnV Φ) are within prescribed ranges. Our results show that for a temperature excess in the range 400-700 K, a combined enrichment in iron and perovskite is more likely to explain LLVSP than recycled MORB (Figure 2). In this temperature range, the likelihood of simultaneously get between -3.0 ≤ dlnV S ≤ -1.0% and 0.0 ≤ dlnV Φ ≤ 1.0%, as expected from seismic tomography, is high (> 0.6) for material enriched in iron and perovskite, and very low (< 0.1) for recycled MORB. For higher temperature excess (1000 K and more), MORB explain observations better, but such large temperature excesses are inconsistent with both petrological data and numerical modeling of thermo-chemical plumes. As an additional test, we calculated the seismic velocity anomalies induced by the distribution of temperature and composition predicted by a recent model of thermo-chemical convection. In this model, large reservoirs of dense material are generated at the bottom of the system. These structures remain stable during a period of time larger than the age of the Earth, and they induce strong chemical density anomalies. Thermo-chemical reservoirs clearly have different seismic signatures depending on their assumed composition (Figure 3). If they consist of MORB, thermo-chemical reservoirs appear faster than average for both V S and V Φ, in contradiction with seismic tomography. By contrast, if they consist of material enriched in iron and perovskite (here, by 3.0% and 18%, respectively, compared to the regular mantle), thermo-chemical reservoirs appear slower than average for V S and faster for V Φ. The seismic signatures we calculated clearly show that the chemical component in LLVSP unlikely consists of highpressure MORB, but rather of a material enriched in iron and perovskite. A remaining question concerns the origin of such reservoirs. A possible hypothesis is that LLVSP result from the partial differentiation of the mantle early in the Earth's history, and subsequent interaction with mantle convection. Interestingly, this hypothesis is supported by the specific signatures of Ocean Island Basalts (OIB) in rare gases and trace elements, which suggest the presence of reservoirs of undegassed material in the deep mantle. MORB may however reach the bottom of the mantle, as suggested by tomographic images of slabs, in which case they should be, according to our results, distinct from LLSVP. These MORB, together with variations in the topography of the phase transition to post-perovskite (a high-pressure phase of perovskite), may slightly modify the thermo-chemical interpretation of seismic tomography. To fully explain geophysical and geochemical constraints, future models of thermo-chemical convection should thus include two chemical sources (recycled crust and primitive reservoirs), and the post-perovskite phase.
❷ Likelihoods of relative seismic anomalies as a function of temperature anomalies. Two types of chemical heterogeneities are considered, MORB (blue curves), and material enriched (compared to horizontally average mantle) in iron and (Mg,Fe)-perovskite by 1.5% and 9.0%, respectively (orange curves). For each chemical source, we represent the likelihood that shear-wave velocity anomaly (dlnV S) is between -3.0 and -1.0% (dark curves), and the combined likelihood for shear-wave and bulk-sound (dlnV Φ) velocities to lie between -3.0% and -1.0% and 0 and 1.0%, respectively (light curves). Calculations are made in the depth layer 2700-2880 km.
❸ Relative shear-wave (dlnV S) and bulk-sound (dlnV Φ) velocity anomalies predicted by thermo-chemical convection. Represented anomalies are average in a collection of models obtained by varying seismic sensitivities according to their distribution, and the superadiabatic temperature jump in the range 2000-3000 K. Vertical and lateral resolution are degraded to those of seismic tomography. Two types of chemical heterogeneities are considered, MORB (top), and material enriched (compared to pyrolitic mantle) in iron and (Mg,Fe)perovskite by 3% and 18%, respectively (bottom).
▍Publication Earth and Planetary Science Letters 349-350 (2012): 198-208.
23
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Division of Mathematics and Physical Sciences
Revealing the Stereo-specific Chemistry of the Reaction of Cl with Aligned CHD3(v 1=1) Fengyan Wang1, Kopin Liu1,2*, and T. Peter Rakitzis3 Institute of Atomic and Molecular Sciences, Academia Sinica, Taiwan Department of Chemistry, National Tsing Hua University, Taiwan 3 Institute of Electronic Structure and Laser, Greece 1 2
Abstract
The concept of geometrical constraints and steric hindrance in reactions is deeply implanted in a chemist's chemical intuition. Yet, a true three-dimensional view of these steric effects has not, until now, been experimentally realized in full for any chemical reaction. Here we report the complete three-dimensional characterization of the sterics of a benchmark polyatomic reaction by measuring the dependence of the product state-resolved angular distributions on the spatial alignment of the reactive bond in a crossed molecular beam experiment. The results prove the existence of two distinct microscopic reaction mechanisms. Detailed analysis reveals that the origin of the stereodynamics in the HCl(v=0) + CD3(00) product channel can be captured by a textbook line-of-centers collision model. In contrast, a time-delay pathway, including a sharp switch from in-plane to out-of-plane scattering in the forward direction, appears to be operative in forming the excited HCl(v=1) + CD3(00) product pair.
Stereo-specificity, i.e., the influence of collision geometries on chemical reactions, is one of the key concepts in chemical reactivity and has been studied over the past half century. Most of the studies reported so far have been focused on the steric factor that affects the total reaction cross sections or rates. The results showed convincingly that reactivity can indeed be influenc ed by the alignment or the orientation of a reagent, in line with chemical intuition. As elegant as those integral cross section measurements are, a full three-dimensional description of how the geometry of a collision affects chemical reactivity is still lacking. The key to elucidating the steric effects in three dimensions is to determine how the product angular distribution changes with the direction from which the reactants approach, namely, the angular correlation. A few attempts have been made for such measurements, however, on account of experimental constraints, those studies could provide only a fragmented glimpse of the angular correlation. Here, we present the first complete set of experiments needed to fully characterize the steric requirement for any chemical reactions. We chose the benchmark polyatomic reaction of Cl(2P3/2) + CHD3(v1=1) HCl(v) + CD 3 (v=0) to illustrate our experimental method and to demonstrate the information contents unobtainable by any other means. By exploiting the polarization of the infrared (IR) pumping laser to align the vibrationally excited CHD3(v1=1) reactant and by using the time-sliced ion imaging technique to interrogate the dominant CD 3(v=0) products in a crossed-beam experiment, we were able to unravel the entangled angular correlations from a set of product images
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❶ Three normalized raw images at E c=3.8 kcal mol -1 for IR laser polarization (the red double-arrows) directed along three orthogonal axes (x, y, and z) as labeled. The forward scattering angle 0o denotes the initial CHD3 direction in the center-of-mass collision frame. The three images display vastly different appearances, showing striking dependences on IRpolarization directions and thus signifying huge steric effects from reagent alignment. Lower-left panel shows the 2D product speed distribution in the x-z scattering plane for the three polarization cases with the same color codes as the image labels.
acquired under multiple crossed-beam geometries, keeping all at the same collision energy (E C ). The detailed analysis of the data provides a clear stereoview of how the reaction proceeds, and unveils lucidly the mechanistic origin of the observed stereo-specific reactivity. Figure 1 shows three representative difference images sliced through the scattering plane xz at E C = 3.8
a
b
c
❷ Comparison of the experimentally determined PDDCSs with the predictions from a LOC model, and a three-dimensional visualization of how the reaction proceeds. (a) Summary of the polarization-dependent differential cross sections,s2 (θ), of the pair-correlated CD3(00) + HCl(v=1) (upper) and CD3(00) + HCl (v=0) channels (lower). (b) The renormalized PDDCS of the two product channels and the comparison with the line-of-centers (LOC) model (the blue curves) results for HCl (v=0). (c) A cartoon-type representation of the experimental s2 (θ)/so(θ)values at three product scattering angles to illustrate the angular correlation between the HCl (v=0) product recoil directionθand initial C-H bond axis direction. Atθ=180o, the values of, s2(θ)/so(θ),s2 (θ)/so (θ), and s2+(θ)/so(θ), strongly suggest r//k. Accordingly, the scattering favors collinear rebound recoil. Atθ=90o, the sideways-scattered product is dominated by collisions of slightly out-of-plane and with the C-H bond pointing~45o toward the approaching Cl atom. Atθ= 45o, the in-plane, side-on attack yields the products in the forward hemisphere.
kcal mo1-1. The image appearance changes drastically with the IR polarization direction. Also shown in Fig. 1 are the normalized product speed distributions with the IR-polarization lying along x, y, and z axes in the scattering frame, respectively. Clearly, the correlated HCl vibrational distribution depends sensitively on the reactant approaching geometry: The end-on collision (E IR // z) yields a colder distribution, and the two side-on geometries also differ markedly from each other with E IR// y substantially hotter than E IR//x, signifying an enormous azimuthal dependence. The angular distributions of the correlated HCl(v=1) and HCl(v=0) products are clearly revealed from the three images shown in Fig. 1 for the x, y, and z polarizations. Again, their distributions are remarkably distinct. In the case of HCl(v=0) – the outer ring feature, the end-on attack yields predominantly a backwardpeaking distribution, whereas the coplanar side-on collision (x-polarization) gives a prominent sideways feature, which differs markedly from the out-of-plane side-on attack (y-polarization). Such sharply contrasting angular distributions not only reinforce the breakdown of cylindrical symmetry observed in the correlated vibrational distributions, but also reveal the underlying stereo-specificity hidden in the conventional scattering experiment for an unpolarized reactants. As to HCl(v=1) -the inner ring feature, the major differences under different polarizations are the extent of the forward peaking with the (out-of-plane) y-polarization producing the sharpest.
Presented in Fig. 1 is only three special cases; additional images recorded under different experimental geometries enable us to obtain a fuller picture. The detailed analysis of data then provides a clear stereoview of how the reaction proceeds, and unveils lucidly the mechanistic origin of the observed stereo-specific reactivity, as demonstrated in Figure 2. Shown in Figs. 2a and 2b are a complete set of the so-called polarization dependent differential cross sections (PDDCS),Sk (θ); collectively, they provide a vehicle to portrait the directional properties in the bond-breaking and bond forming transformation, as elucidated in Fig. 2c. More than 45 years has been passed since the oriented/aligned molecular beam was introduced to explore the steric effects in elementary chemical reactions. Yet, a true three-dimensional description of the stereo-requirements in a chemical reaction had not been experimentally realized, until now. We have demonstrated that a complete polarization-dependent differential cross sections measurement allowed, for the first time, a clear stereo-view of how the reaction proceeds. The experimental method developed here for uncovering the intrinsic directional properties of a chemical reaction proves quite general and robust, and thus should be applicable to many other scattering studies, including the angular correlation with polarized products.
▍Publication Nature Chemistry 4 (2012): 636-641.
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Division of Mathematics and Physical Sciences
The Acoustic Emotion Gaussians Model for Emotion-based Music Annotation and Retrieval Ju-Chiang Wang1,2, Yi-Hsuan Yang2,3*, Hsin-Min Wang2,3, and Shyh-Kang Jeng1 Department of Electrical Engineering, National Taiwan University, Taiwan Institute of Information Science, Academia Sinica, Taiwan 3 Research Center for Information Technology Innovation, Academia Sinica, Taiwan 1 2
Abstract
One of the most exciting but challenging endeavors in music research is to develop a computational model that comprehends the affective content of music signals and organizes a music collection according to emotion. In this paper, we propose a novel acoustic emotion Gaussians (AEG) model that defines a proper generative process of emotion perception in music. As a generative model, AEG permits easy and straightforward interpretations of the model learning processes. To bridge the acoustic feature space and music emotion space, a set of latent feature classes , which are learned from data, is introduced to perform the endto-end semantic mappings between the two spaces. Based on the space of latent feature classes, the AEG model is applicable to automatic music emotion annotation, emotion-based music retrieval, and emotion-based music video composition. Our results show that the AEG model outperforms the state-of-the-art methods in automatic music emotion annotation. This work won the first prize of the 2012 ACM Multimedia Grand Challenge.
One of the most exciting but challenging endeavors in music research is to develop a computational model that comprehends the affective content of music signals and organizes a music collection according to emotion. Such a model is desirable as the pursuit of emotional experience is the primary motivation for music listening. Behavioral studies have also identified emotion as one of the most important attributes used by people for music retrieval. Automatic annotation of music emotion is challenging because the perception of emotion is in nature subjective. Oftentimes people perceive differently when listening to the same song. Consequently, one
cannot assume that there is an objective, single ground truth label that applies equally well to every listener. Instead, one needs to learn directly from multiple labels provided by different annotators and present as the final result a soft (probabilistic) emotion assignment instead of a hard (deterministic) one. In this paper, we propose a novel acoustic emotion Gaussians (AEG) model that realizes a proper generative process of music emotion perception in a probabilistic and parametric framework. The AEG model learns from data two sets of Gaussian mixture models (GMMs), namely acoustic GMM and VA GMM , to describe the low-level acoustic feature space and high-level emotion
❶ Illustration of the acoustic emotion Gaussians framework for emotion-based music annotation and retrieval. Music emotion distribution can be generated from the acoustic features of music.
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space, respectively. A set of latent feature classes is introduced to play the end-to-end linkage between the two spaces and aligns the two GMMs. As a principled probabilistic model, AEG is applicable to both automatic music emotion annotation and emotion-based music retrieval. The proposed AEG framework has three additional advantages. First, as a generative model, AEG permits easy and straightforward interpretation of the model learning and semantic mapping processes. Second, as AEG mainly involves light-weight computations of emotion prediction, it can track the moment-to-moment emotion distributions of a music piece in real-time. Third, due to its parametric and probabilistic nature, AEG provides great flexibility to future extension, such as personalizing the AEG model via model adaptation techniques or incorporating music tags for advanced music browsing and retrieval purposes. A comprehensive evaluation of automatic music emotion annotation on two emotion annotated music corpora has demonstrated the effectiveness of AEG over state-of-the-art methods. Moreover, we have also demonstrated the potential application of AEG for emotion-based music retrieval. We have also extended AEG to jointly learn the tripartite relationship among music, video, and emotion from an emotion-annotated corpus of music
videos, and applied the model to emotion-based music video composition. The model is applied to a piece of music (or a video sequence) to predict its emotion distribution in a continuous emotion space from the corresponding low-level acoustic features (or visual). As the AEG is flexible, the model can be personalized via online model adaptation. Finally, music and video are matched by measuring the similarity between the two corresponding emotion distributions, based on a distance measure such as Kullback-Leibler (KL) divergence. The system is effective and efficient and will likely be incorporated into mobile devices in the near future. This work won the first prize of the 2012 ACM Multimedia Grand Challenge.
❷ The flowchart of the emotion-based music search retrieval using an emotion-related query.
❸ Illustration of the extended acoustic visual emotion Gaussians framework for emotion-based music video composition.
▍Publication Proceedings of ACM Multimedia (2012): 89-98.
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Division of Life Sciences
Distinct Phytochrome Actions in Non-vascular Plants Revealed by Targeted Inactivation of Phytobilin Biosynthesis Yu-Rong Chen, Yi-Shin Su, and Shih-Long Tu Institute of Plant and Microbial Biology, Academia Sinica, Taiwan
Abstract
The red/far-red light photoreceptor phytochrome mediates photomorphological responses in plants. For light sensing and signaling, phytochromes need to associate with chromophores. Biosynthesis of chromophores requires ferredoxin-dependent bilin reductases (FDBRs). It was shown that LONG HYPOCOTYL 2 (HY2) is the only FDBR in flowering plants. However in the moss Physcomitrella patens , we identified a second FDBR producing an alternative chromophore for phytochromes. We named the newly-found enzyme phycourobilin synthase (PUBS). PUBS can only be found in green algae, mosses, and lycophytes, suggesting this gene is important for green plants to adapt the light-rich environment during land colonization. We further identified phytochrome-regulated genes in Physcomitrella . Results reveal that moss phytochromes efficiently re-program gene expression for phototrophic growth in the light. This approach allows, for the first time, to have a global view of phytochrome-mediated gene regulation in nonvascular plants.
Photosynthetic organisms develop sophisticated photoreceptor systems to regulate their growth and development. Phytochromes are the major class of photoreceptors that mainly absorb red and far-red light, to display differential photosensory activities for regulating physiological responses. Light perception of phytochromes depends on the association with open-chain tetrapyrroles as the chromophore. Biosynthesis of tetrapyrroles requires ferredoxin-dependent bilin reductases (FDBRs), which reduce biliverdin IXα (BV) at different double bond positions. Time-course of BV reduction activity of PUBS. (A) Spectrophotometric time course of BV reduction by The greatest diversity of the BV- ❶ PUBS under anaerobic single turnover conditions. (B) Reaction mixture aliquots from the steady-state assay metabolizing FDBR members of PUBS were withdrawn every 150 seconds and analyzed by reverse phase HPLC. (C) Reaction catalyzed are found in the cyanobacteria. by PUBS. Land plants are thought to transit peptide (tp) at the N-terminus of a FDBR domain possess only HY2 . Mutations in the HY2 gene lead to with strongest similarity to 15,16-dihydrobiliverdin:ferre the loss of all photoactive phytochromes in plants, which doxin oxidoreductase (PebA), a FDBR usually found in results in the severe disruption in photomorphogenesis. cyanobacteria and red algae. To confirm that the pebA In higher plants, HY2 is the only FDBR like gene from Physcomitrella encodes a functional for biosynthesis of the phytochromobilin (PΦB) protein, the recombinant, tp-truncated protein was chromophore. However in the moss Physcomitrella expressed in E. coli and purified. As shown in Figure 1A, patens , we found an additional FDBR gene. The encoded the PebA-like protein initially converted BV to produce protein of this gene possesses a putative chloroplast
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15,16-DHBV that was subsequently converted to a new product. The absorption spectrum of the new product was identical to that of phycourobilin (PUB) with maximum absorbance at 492 nm. Combined with data from mass spectroscopy, we conclude that the new product is PUB. The PebA-like protein was named PUBS for phycourobilin synthase. PUBS is only present in chlorophytes, bryophytes, and lycophytes, implicating the loss of this gene during evolution of seed plants. As the function of PΦB in photomorphogenesis is well known, our observations raised the possibility that PUB is also important for photomorphogenesis. Gene targeting was performed to disrupt PpPUBS and PpHY2 loci in Physcomitrella and single- and double-knockout ❷ Phenotypes of gene-targeted knockout mutants. (A) Twelve-day-old protonemata mutants were obtained. Phenotypes of single and of wild-type (WT), pubs, hy2 and pubs hy2 grown under white, red and blue light double pubs hy2 mutants grown under white, red conditions are shown. (B) Thirty-day-old gametophores of wild type (WT), pubs, hy2 and pubs hy2 grown under white (WL), red (RL) and blue (BL) light conditions are and blue light conditions were analyzed at different shown. (C to E) Stem length of gametophores from WT and mutants grown under developmental stages. As shown in Figure 2A, white (C), red (D) and blue (E) light conditions. protonemal colonies of the wild type, pubs and hy2 single mutants all had a similar diameter. By contrast, the double mutant grew more slowly and exhibited shorter protonemata. Such phenotypes were much stronger under red light, indicating that the double mutant is severely defective in red light sensing. We also characterized the gametophore phenotypes of single and double mutants. While gametophores of pubs and hy2 were indistinguishable from that of the wild type, gametophores of the double mutant grown under white light showed pale green and stem elongation phenotypes (Figure 2B, top panel). Stems of the double mutant pubs hy2 were approximately 2 times longer than that of wild type and both single mutants (Figure 2C). Gametophores of the pubs hy2 double mutant showed severe growth arrest under red light (Figure 2B, middle panel). In contrast, the morphology of wild type, single and double mutant were almost identical under blue light (Figure 2B, middle panel and Figure 2E). The data indicate that both FDBRs are required for leaf development and for ❸ Expression profiles of red light-regulated genes in wild inhibition of stem elongation. type and pubs hy2 double mutant. Log 2-normalized fold changes of 1095 red light-induced genes and 1107 red lightSince phytochromes regulate gene expression in flowering repressed genes obtained from wild-type datasets were plants, we compared the red-light regulated transcriptomes of wild calculated. Heat maps of Log2-normalized fold changes of these genes in wild type (WT) and pubs hy2 double mutant type and the pubs hy2 double mutant. Next-generation sequencing were shown. The scale of expression is shown in the center. technology was chosen for the transcriptome profiling. A total of 2202 genes in the wild type were differentially expressed after 1-hour red light exposure. Of these, approximately half were up-regulated and half were down-regulated. Among the 1095 up-regulated genes, 70% showed reduced expression under red light in the pubs hy2 double mutant. Of the 1107 down-regulated genes, 90% were also misregulated in the double mutant (Figure 3). These results reveal a severe deficiency in red light sensing when both HY2 and PUBS were inactivated. In conclusion, our study shows that non-vascular plants possess a novel member of the FDBR family, PUBS. The results show that PUBS and HY2 are both involved in photomorphogenesis of Physcomitrella under red light. The pubs hy2 double mutant allows us, for the first time, to ascertain the phenotype of a phytochrome null in a nonvascular plant. By comparing transcript levels of red light-responsive genes in wild type and pubs hy2 , we identified putative target genes of moss phytochrome signaling.
▍Publication Proceedings of the National Academy of Sciences of the United States of America 109 (2012): 8310-8315.
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Division of Life Sciences
BMP and Delta/Notch Signaling Control the Development of Amphioxus Epidermal Sensory Neurons: Insights into the Evolution of the Peripheral Sensory System Tsai-Ming Lu1, Yi-Jyun Luo1, and Jr-Kai Yu*1, 2 1 2
Institute of Cellular and Organismic Biology, Academia Sinica, Taiwan Institute of Oceanography, National Taiwan University, Taiwan
Abstract
Amphioxus is a basal chordate that has a dorsal central nervous system (CNS) and a peripheral nervous system (PNS) comprising several types of epidermal sensory neurons (ESNs). We show that a proneural basic helix-loop-helix gene (Ash ) is co-expressed with the Delta ligand in the ESN progenitor cells. Using pharmacological treatments, we demonstrate that Delta/Notch signaling is involved in the specification of amphioxus ESNs from their neighboring epidermal cells. We also show that BMP signaling functions upstream of Delta/ Notch signaling to induce a ventral neurogenic domain. This patterning mechanism is highly similar to that of the peripheral sensory neurons in the protostome and vertebrate model animals, suggesting that they may share the same ancestry. We hypothesize that during chordate evolution, the PNS progenitors may have been polarized to different positions in various chordate lineages due to differential regulation of BMP signaling in the ectoderm.
The evolutionary origin of the central nervous system (CNS) and peripheral nervous system (PNS) in bilaterian animals has been a topic of great interest. During the last two decades, many discoveries have i d e nt i f i e d r e m a r ka b l e si m i l a r i ti e s in gene expression and conserved signaling pathways in the anterior/ posterior and medial/lateral patterning of the CNS between the protostome and chordates. These findings have led to the hypothesis that a single CNS evolved in the basal bilaterians. In addition to the CNS, both protostomes and chordates have a PNS with ectodermal sensory neurons. ❶ Adult and embryonic stages of amphioxus. (A) Photograph of a living adult female animal and a corresponding diagram of the major anatomical features. (B) Unfertilized egg; (C) gastrula; (D) Interestingly, most of the neurons of the neurula; (E) 36-hour larva. vertebrate PNS are derived from two ectodermal tissues, the neural crest segmented somites, and pharyngeal gill slits) with and the neurogenic placodes, which originate from the vertebrate animals (Fig. 1). In addition to the dorsal boundary between the CNS and the epidermal ectoderm. CNS, amphioxus also has a peripheral nervous system However, the neural crest and the neurogenic placodes comprising several types of sensory neurons. Among are usually considered as vertebrate innovations, and these amphioxus sensory neurons, the solitary type I their evolutionary origins remain largely unresolved. receptor cells are the most abundant population of the To gain more insights into the evolution of the epidermal sensory neurons (ESNs) and are scattered nervous system, we focus on the mechanisms of along the bodies of developing amphioxus larvae and neurogenesis in the cephalochordate amphioxus. adults (Fig. 2). The cell body of the receptor is located Amphioxus is an invertebrate chordate that shares key within the epidermis, and a long axon from the base of chordate characteristics (a dorsal CNS, notochord,
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the cell body innervates into the CNS. During the early neurula stage, these ESNs differentiate from the ventral ectoderm and are first characterized by the expression of pann e u r a l m a r k e r Hu/Elav . Subsequently these ❷ Distribution of epidermal sensory neurons (ESNs) in amphioxus. (A, B) Confocal images differentiating ESNs of L3 stage larva (48 hours post-fertilization). delaminate from the The axonal structure is labeled with antiacetylated tubulin antibody (red). Nuclei are ectoderm and invaginate labeled with DAPI (blue). Muscle fibers and into the sub-epidermal myotome organization are visualized by actin staining (green). (C, D) Images show that each space to migrate toward the individual ESN (white arrows) resides in the dorsal side of the neurula. peripheral epidermis and projects one axon (arrowhead) towards the CNS. Using embryonic ontogeny and expression data for several homologues of placode marker genes, it has been speculated that these amphioxus ESNs are homologous to vertebrate placode-derived neurons. However, the molecular mechanism controlling the specification of amphioxus ESNs remains unclear, and this situation has impeded our understanding of the relationship of these ESNs to the peripheral sensory neurons in other animals. To address this issue, we set out to determine the developmental mechanisms underlying the formation of the ESNs in amphioxus. By immunostaining and gene expression patterns of neuronal markers, we characterize the axonal structure, innervation pattern, and ontology of the peripheral nervous system of amphioxus at embryonic and larval stages. We ❸ Schematic models for the development of the amphioxus ESNs. During embryogenesis, inhibition of BMP signaling by BMP antagonists also show that high BMP signaling level is required induces the formation of the CNS in the dorsal ectoderm (blue), while for the induction of a ventral epidermal domain for high levels of BMP signaling induce a putative ESN progenitor field (yellow) in the ventral ectoderm, which is approximately equivalent to generating peripheral ESNs in amphioxus embryos, the Tlx expression domain. Within this ESN progenitor field (yellow, and subsequently proneural bHLH gene Ash and expressing Tlx ), Ash and Delta are expressed in specific cells to promote the differentiation of individual ESN cells (green) through Delta-Notch Delta/Notch signaling are involved in the specification mediated lateral inhibition. of individual ESNs within this domain (Fig. 3). This patterning mechanism is highly reminiscent to that for certain vertebrate neurogenic placodes and ascidian ventral epidermal sensory neurons, suggesting that they may share the same ancestry. Our results demonstrate that conserved Delta-Notch and BMP signaling pathways govern respectively the specification and distribution of ESNs in amphioxus. Our data are consistent with findings from Drosophila and Platynereis which conclude that the motor neurons and interneurons in the CNS develop from the non-BMP side of the body, while the formation of the peripheral sensory neurons are positively regulated by BMP signaling. This suggests that the function of biphasic BMP signaling in CNS and PNS development exists in the bilaterian common ancestor. Moreover, our results provide strong evidence to support the hypothesis that the amphioxus ESNs are possible homologues of vertebrate placode-derived neurons, and the ventral ectoderm of the amphioxus embryo is a neurogenic region that may be homologous to the pre-placodal field of vertebrates. Thus, our findings reveal a possible link among the PNS of major bilaterian lineages. We hypothesize that during chordate evolution, the PNS progenitors may have been polarized to different positions in various lineages due to differential regulation of BMP signaling in the embryonic ectoderm. Further comparative studies will facilitate our understanding of the modification of the PNS during chordate evolution.
▍Publication Development 139 (2012): 2020-2030.
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Division of Life Sciences
Changing Trends in the Prevalence of Common Mental Disorders in Taiwan: A 20-year Repeated Cross-sectional Survey Tiffany S.-T Fu1, C.-S Lee2, David Gunnell3, W.-C Lee4, and Andrew T.-A Cheng1 Institute of Biomedical Sciences, Academia Sinica, Taiwan Department of Psychiatry, Taipei Mackay Memorial Hospital, Taiwan 3 School of Social and Community Medicine, University of Bristol, UK 4 Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taiwan 1 2
Abstract
Common mental disorders (CMDs) include depressive and anxiety disorders that occupy the vast majority of psychiatric morbidity in the general population. In this study, five independent cross-sectional surveys of Taiwanese respondents (≧18 years of age) were carried out in 1990, 1995, 2000, 2005, and 2010 (N=9079 in total). Survey measures included the 12item Chinese Health Questionnaire (CHQ), a screening questionnaire for CMDs and physical and socio-demographic risk factors for CMDs. The prevalence of probable CMDs doubled from 11.5% in 1990 to 23.8% in 2010 (time trend p < 0.001). This increase paralleled rises in national rates of unemployment, divorce, and suicide across the five waves. In multivariable regression model, significant risk factors of probable CMDs were being female, ≤ 6 years of education, unemployment, and being in poor physical health with limitations in daily activities. Controlling for these factors in multivariable models did not reduce the secular rise in prevalence of probable CMDs (time trend p < 0.0001).
The term common mental disorders (CMDs) is a broad diagnostic category for non-psychotic depressive and anxiety disorders, that covers most psychiatric morbidity in the general population. CMDs lead to substantial morbidity worldwide. WHO estimates that depression will be the leading cause of disabilityadjusted life years by 2020. The extent of CMDs reflects a population’s mental health and macro-social changes may play an important role for it. This study analyzed data from 9,079 respondents recruited in five independent cross-sectional national surveys in Taiwan carried out in 1990, 1995, 2000, 2005, and 2010 by the Taiwan Social Change Survey (TSCS) funded by the National Science Council. For each wave, the distribution of age and gender is comparable between the responders and the non-responders. Survey measures included the 12-item Chinese Health Questionnaire (CHQ), a screening questionnaire for CMDs and physical and socio-demographic risk factors for CMDs. The CHQ-12 has been widely used in Chinese populations worldwide with acceptable sensitivity and specificity. In this study we classify respondents with total CHQ scores of 3 or more as being likely to have CMDs. The time trend for CMDs screened by CHQ were examined using Cochran-Armitage trend test and multivariable logistic regression model. Trends
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in probable CMDs were compared with trends in national levels of unemployment, divorce, and suicide rates. We obtained data for specific sociodemographic risk factors from the TSCS databank and converted them into categorical variables. We assessed sex, age (18-34, 35-49, 50-64, or ≥ 65 years), marital status (single, married, or previously married [i.e. divorced or widowed]), educational level (> 6 years or ≤ 6 years), and employment status (employed, unemployed, or other). To obtain information on the overall physical health of the respondents, one item in the mental health section of TSCS questionnaire asked whether daily activities (studying, working, housekeeping, etc) had been greatly limited by any physical illness in the past two weeks. Additionally we compared trends in the prevalence of CMDs with those of specific macro-social and health indices. At the time of each survey we retrieved national data on rates of divorce, suicide, and unemployment. The prevalence of probable CMDs rose in each study period except for the last, and more than doubled overall: 11.5% (95% CI 10.2–12.8%) in 1990, 16.0% (95% CI 14.3–17.7%) in 1995, 18.8% (95% CI 16.9– 20.7%) in 2000, 25.6% (95% CI 23.5–27.8%) in 2005, and 23.8% (95% CI 21.9–25.7%) in 2010 (time trend p < 0.001). This increase paralleled rises in national rates of unemployment, divorce, and suicide across
Time trends for common mental disorders (CMDs), divorce and unemployment in Taiwan, 1990 to 2010.
Time trends for common mental disorders (CMDs) and suicide rates in Taiwan, 1990 to 2010.
the five waves. In multivariable regression model, significant risk factors of probable CMDs were being female (adjusted odds ratio [OR] 1.6, 95% CI 1.4–1.8), ≤ 6 years education (adjusted OR 1.3, 95% CI 1.1–1.5), unemployment (adjusted OR 1.4, 95% CI 1.1–1.7), and being in poor physical health with limitations in daily activities (adjusted OR 6.5, 95% CI 5.4-8.0). Controlling for these factors in multivariable models did not reduce the secular rise in prevalence of probable CMDs (time trend p < 0.0001). The study suggests that the significant trend of increase in rates of CMDs over time may at least in part be attributable to the macro-social changes such as the continued decline in the employment market due
to relocation of the labor-intensive industries to China and Southeast Asia, and the recent global economic recession that occurred during the study period. While the effect of personal risk factors for CMDs remained constant over the 20 years, the increase in the unemployment rate (from 1.7% to 5.2%) brought about an increase in rates of CMDs. Deterioration in a number of indicators of social wellbeing has paralleled rises in CMDs and suicide rates in Taiwan. Our findings suggest that mental health is important to overall health and wellbeing. Effective clinical and social preventive measures should be considered during times of economic adversity.
▍Publication Lancet 381 (2013): 235-241.
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Division of Life Sciences
The Evolution of Low Mutation Rates in Experimental Mutator Populations of Saccharomyces cerevisiae Michael J. McDonald1, Yu-Ying Hsieh1,2, Yen-Hsin Yu1, Shang-Lin Chang1,3, and Jun-Yi Leu1 Institute of Molecular Biology, Academia Sinica, Taiwan Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taiwan 3 Molecular Cell Biology, Taiwan International Graduate Program, Institute of Molecular Biology, Academia Sinica, and Graduate Institute of Life Sciences, National Defense Medical Center, Taiwan 1 2
Abstract
Mutation rates are shaped by opposing selective forces, these arise from mutation being the source of both adaptive variation and the deleterious mutations that burden populations. This dichotomy is well illustrated by the evolution of the mutator phenotype, a genome-wide 10-100 fold increase in mutation rate. This phenotype has often been observed in clonally expanding populations exposed to novel or frequently changing conditions. Although studies of both experimental and natural populations have shed light on the evolutionary forces that lead to the spread of the mutator allele through a population, significant gaps in our understanding of mutator evolution remain. Here we use an experimental evolution approach to investigate the conditions required for evolution of a reduction in mutation rate and the mechanisms by which populations tolerate the accumulation of deleterious mutations. We find that after ~6700 generations four out of eight experimental mutator lines had evolved a decreased mutation rate. We plot time course trajectories for the fitness, mutation rates and ploidy of all lines and provide evidence that the accumulation of deleterious mutations leads to selection for reduced mutation rate clones in populations of mutators. Finally, we test the long-term consequences of the mutator phenotype using the cancer drug, Macbecin II, finding that mutator lines follow different evolutionary trajectories, some of which lead to drug resistance.
Although mutator phenotypes are prevalent in some species, their indirect, transient benefit and the relative mosaicism of bacterial mismatch repair genes imply a history of alternation between mutator and nonmutator phenotypes. While the invasion of mutator alleles have been observed upon multiple occasions and antimutator alleles have been identified, the restoration of low mutation rates in populations fixed for the mutator phenotype has yet to be demonstrated in experimental populations. One of the most consistent results of experimental evolution is the steep initial increase in the fitness of a population, a response to the typically unfavorable conditions inflicted upon the focal organism by experimenters. Under these conditions, low mutation rates and low fitness increase the likelihood of fixation of a mutator allele by hitchhiking with a new beneficial mutation. Here we test the expectation that the opposite circumstances- an initially high mutation rate in a high fitness population- could induce selective pressure against high mutation rates. We engineered a haploid mutator strain of Saccharomyces cerevisiae and propagated replicate populations with a population bottleneck of 3×10 4 cells for 6700 generations in an environment to which they were already relatively well adapted. Five out of eight mutator lines (compared to one of the non-mutator lines) decreased in fitness compared
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to the ancestor at some point during the experiment (Figure 1). These results suggest that in this experiment the mutator phenotype is conferring an indirect fitness cost. In order to determine if the deleterious effect of the mutator phenotype had led to the evolution of decreased mutation rates, we performed fluctuation tests on the mutator and non-mutator experimental lines. Four out of eight mutator populations had a significant reduction in their mutation rate. While there was also a general trend towards a decrease in the mutation rate of the non-mutator experimental lines, the reduced power of the assay for distinguishing between lower mutation rates meant it was difficult to discern any significant difference (Figure 2A and 2B). In order to determine how some mutator lines reverted to the reduced mutation rate phenotype, we took a closer look at the fitness trajectories of the mutator lines. We chose two mutation lines (m2 and m8) that had sustained a large decrease in fitness at different time points during the experiment. We measured a mutation rate trajectory for these two lines. A decrease in the mutation rate occurred between generations 3100 and 4700 in line m2, and between generations 5700 and 6700 in line m8, both with a significant decrease in fitness in the interval immediately preceding it (Figure 1, 2C and 2D).
A
B
1
❶ Fitness trajectories of the non-mutator (A) and mutator (B) lines during 6700 generations of experimental evolution.
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❷ Mutation rates of ancestral and evolved strains. Two clones were chosen from each population, transformed with either the adenine (light) or clonat (dark) marked plasmids and then fluctuation tests were performed using at least 16 cultures. Relative mutation rates of mutator (A) and non-mutator (B) strains collected from generation 6700. (C) and (D) indicate the mutation rate trajectory during the course of experimental evolution for lines m2 and m8 respectively. ❸ Growth of experimental lines in the presence of Hsp90-inhibiting drug, Macbecin II. (A) The growth of evolved strains relative to their progenitor strain in the presence of Macbecin II. (B) The growth of non-mutator lines in the presence of Macbecin II was correlated with performance in YPD media without Macbecin II, while (C) growth of the mutator strains in YPD + Macbecin II showed no correlation with growth in YPD.
3
It is possible that the spread of the reduced mutation rate was due to direct selection rather than its reduced likelihood of sustaining deleterious mutations. To test this possibility, we carried out competitive fitness assays between differently marked individuals taken from different time points in lines m8 and m2. In line m8 we found that the reduced mutation rate clone taken from generation 6700 had a 1.19-fold fitness advantage compared to the mutator clone taken from the same line at generation 5700. When one mutator and one reduced mutation rate clones in the m2 population at 3100 generations were competed, the reduced mutation rate clone was found to have a 1.46 fold fitness advantage over the mutator clone. These results suggest that it was not indirect selection that drove the reduced mutation rate clones to fixation in these two lines. Rather, the discovery of such a large difference in fitness between contemporaneous mutator and reduced mutation rate clones suggests that direct fitness effect of the reduced mutator allele may have been responsible. A predicted consequence of accumulated deleterious mutations is the evolution of enhanced physiological buffering for unstable proteins. The most well known buffering system is the heat shock protein Hsp90. In order to investigate the importance of Hsp90
to the evolved lines we tested the effects of the Hsp90 inhibitor Macbecin II. This drug is expected to be harmful to cells that have sustained a large number of mutations because it will remove the buffering effect of Hsp90, unmasking the effects of deleterious mutations. Figure 3A shows that, in general, non-mutator experimental lines grew better in the presence of Macbecin II relative to their progenitor, while mutator lines showed a variable response to the drug. The finding that mutator populations in this study exhibit varying dependence on heat shock protein buffering systems suggests that alternative physiological buffering mechanisms or compensatory mutations may be able to ameliorate the effects of mutation accumulation (Figure 3B and 3C). The mutator phenotype has long been hypothesized to play an important role in cancer progression. Mutation shock therapies, implemented using drugs such as Macbecin II have been employed to unmask the deleterious mutations accumulated by cancer cells. Our results indicate that even cancerous growths that have accumulated many mutations may have varying sensitivities to such drugs.
▍Publication Current Biology 22 (2012): 1235-1240.
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Division of Life Sciences
Crystal Structure of Staphylococcus aureus Transglycosylase in Complex with a Lipid II Analog and Elucidation of Peptidoglycan Synthesis Mechanism Chia-Ying Huang1,2, Hao-Wei Shih1,3, Li-Ying Lin1, Yi-Wen Tien1, Ting-Jen Rachel Cheng1, Wei-Chieh Cheng1, Chi-Huey Wong1,2, and Che Ma1,2 Genomics Research Center, Academia Sinica, Taiwan Institutes of Microbiology and Immunology, National Yang-Ming University, Taiwan 3 Department of Chemistry, National Taiwan University, Taiwan 1 2
Abstract
Bacterial transpeptidase and transglycosylase on the surface are essential for cell wall synthesis, and many antibiotics have been developed to target the transpeptidase; however, the problem of antibiotic resistance has arisen and caused a major threat in bacterial infection. The transglycosylase has been considered to be another excellent target, but no antibiotics have been developed to target this enzyme. Here, we determined the crystal structure of the Staphylococcus aureus membrane-bound transglycosylase, monofunctional glycosyltransferase, in complex with a lipid II analog to 2.3 Å resolution. Our results showed that the lipid II-contacting residues are not only conserved in WT and drug-resistant bacteria but also significant in enzymatic activity. Mechanistically, we proposed that K140 and R148 in the donor site, instead of the previously proposed E156, are used to stabilize the pyrophosphate-leaving group of lipid II, and E100 in the acceptor site acts as general base for the 4-OH of GlcNAc to facilitate the transglycosylation reaction. This mechanism, further supported by mutagenesis study and the structure of monofunctional glycosyltransferase in complex with moenomycin in the donor site, provides a direction for antibacterial drugs design.
Peptidoglycan is a major component of the bacterial cell wall and essential for bacteria to survive. Bacterial transpeptidase and transglycosylase (TG) on the cell surface are the two key enzymes responsible for making peptidoglycan. Many current antibiotics have been developed to target the transpeptidase, but the problem of antibiotic resistance has arisen and caused a major threat in treating bacterial infection, such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). When a thorough examination is done toward both Gram-positive and Gram-negative bacteria, including MRSA, VRE, and drug-resistant bacteria of Acinetobacter baumannii,
Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa, and Mycobacterium tuberculosis , it appeared
that none has a gene mutation in the transglycosylase area. The transglycosylase has been considered to be another excellent target, but no antibiotics have been developed to target this enzyme. The research team at the Genomics Research Center, Academia Sinica has solved the structure of Staphylococcus aureus transglycosylase, together with its substrate lipid II analog, to provide not only a basis for understanding the mechanism of how the enzyme transglycoslase takes lipid II and makes it into peptidoglycan, but also a foundation for new antibiotic design against transglycosyase.
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In the synthesis of bacterial cell wall, the peptidoglycan transglycosylation by the enzyme TG takes place through polymerization of lipid II substrates. The substrate-binding site of TG has been proposed to consist of a glycosyl acceptor site, where the disaccharide monomer lipid II binds, and a glycosyl donor site, where another lipid II binds and accommodates the growing sugar chain. The only known natural product that directly inhibits the function of TGs is moenomycin, which binds to the glycosyl donor site. Unfortunately, moenomycin cannot be given to humans due to its poor pharmacokinetic properties. The molecular interaction between lipid II and the glycosyl acceptor site of TG is needed in order to elucidate the mechanism of lipid II polymerization and also to serve as a new basis for the development of inhibitors of TG. In this study, we designed lipid II analogs and used to co-crystallize with S. aureus membrane-bound monofunctional glycosyltransferase (MGT) by bicelle method to unveil the structure of MGT and, together with mutagenesis analysis, to elucidate the mechanism of transglycosylation reaction. This work provides the atomic information for understanding the key step of how the cell wall of bacteria, peptidoglycan, is built, and paves the way for structure-based antibiotic design against transglycosylase.
▲ Stereo and schematic view of interaction between Staphylococcus aureus transglycosylase and Lipid II analog. (A) Stereo view of the electron density map. (B) Hydrogen-bonding network of the interaction.
▍Publication Proceedings of the National Academy of Sciences of the United States of America 109 (2012): 6496-6501.
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Division of the Humanities and Social Sciences
Jiagu Wenzi Bian (Understanding the Oracle Bone Inscriptions) Zong-Kun Li Institute of History and Philology, Academia Sinica, Taiwan
Understanding the Oracle Bone Inscriptions contains entries for all of the Yin Ruin oracle bone
Abstract
characters and words known of as of 2010. Each character has been accurately facsimiled by hand with the original style and dimensions. The book also contains a collection of the most recent related research, making it the most extensive compendium of oracle bone inscriptions to date. The book contains entries for 46,635 characters and variant forms, leaving out no significant variant. There are also entries for 4,378 words. This number represents an answer to the question of how many oracle bone words there are, putting to rest a centuryold debate. The meaning of about 38% of these words is known, and approximately a third correspond to modern words. The back of the book contains five indexes and three charts.
The study of the form and style of the characters of oracle bone inscriptions is an important area of the research of oracle bones and Chinese paleography. Scholars have amassed a considerable amount of research in this area, yet it has its limitations, namely in the lack of source material and biases related to the facsimile and interpretation of characters. Making use of the increasing number of excavated materials and continued improvements in research, Understanding the Oracle Bone Inscriptions 甲骨文字編 brings together the results of new research, and represents the most extensive work on oracle bone script to date.
Understanding the Oracle Bone Inscriptions
represents twenty years of effort on the part of the author. It is not merely an expansion or extension of previous related writings, but rather a new work carefully written and compiled in accordance with current disciplinary needs and standards. Over the two decades during which the book was compiled and edited, the author undertook the most comprehensive and systematic investigation to date of the several tens of thousands of oracle bones. The book contains entries for all of the Yin Ruin oracle bone characters and variants known of as of 2010. Each is reproduced accurately by hand with the original style and dimension. Some entries rely on careful extrapolations based on an examination of oracle bones. These are carefully drawn copies and not scanned digital reproductions. This is because rubbings of oracle bones are often unclear and scans of the originals are just machine copies. That is, only accurate drawings are
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Understanding the Oracle Bone Inscriptions
able to convey the views of the author and adequately express the results of his research. The entire book contains 46,635 character forms, leaving out no significant variant form. The book is not organized in the same way as Shuowen Jieshi 說文解 字. This is because the attempt to organize oracle bone characters based on those of lesser seal script often leads to ill-fitting and forced categorizations. Instead, the book organizes oracle bone characters based on their own radicals and phonetic parts. Chief radicals are established for oracle bone characters such that they may be categorized by type. Each entry for a word cites its source(s) and is arranged by era. This allows researchers to verify the origin of rubbings, and makes the change of each character’s style over the ages immediately apparent through the use of charts.
The book also contains a careful treatment of the classification of characters. The book contains 4,378 words, as well as 52 entries for damaged or partial inscriptions, 26 facsimiles of previous drawings, and 328 entries for composed characters that seem to comprise multiple parts but are treated as a single entry. It is particularly important that the number of words is 4,378. This is not merely a number. Rather, it answers a question that has long been central to the study of oracle bones and Chinese paleography: How many words are found on the oracle bones? In the past, scholars have proposed many divergent speculative answers to this question. The highest and lowest numbers differ by 50%. Yet these were all guesses without any factual basis. Thus, in addition to presenting oracle bone script in a form faithful to the originals, the book also precisely answers the question of how great the total number of oracle bone words is by providing evidence, and thus puts to rest a century-old mystery.
The meaning of about 38% of oracle bone words can be discerned. (This includes words that no long exist today, but that may be comprehended, such as names of people and places.) About a third of the words correspond to modern ones. The back of the book has indexes organized by chief radical, number of strokes, Hanyu Pinyin, and Zhuyin Fuhao. In the two stroke order indexes, characters with the same number of strokes are organized by hanyu pinyin and zhuyinfuhao respectively. This careful design makes for especially convenient searches. The book also includes a chart that matches the numbering of entries with those in Yinxu Jiagu Keci Leizuan 殷墟甲骨刻辭類纂 and Jiaguwen Bian 甲骨文編 for the user’s ease of cross reference. This scholarly work both represents the most extensive compendium of oracle bone data and responds to the most recent research. The characters of the oracle bones and their variant forms could not be more splendidly presented to the reader.
▍Publication Beijing: Zhonghua Book Co., 2125 pages, 2012.
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Division of the Humanities and Social Sciences
Qian Qianyi "Bingta xiaohan zayong" Lunxi (A Study of Qian Qianyi's "Forty-six Miscellaneous Poems to Dispel Cold on My Sickbed") Lawrence C. H. Yim Institute of Chinese Literature and Philosophy, Academia Sinica, Taiwan
Abstract
This book studies the last poem series, “The Sickbed Poems,” of the great scholar-poet Qian Qianyi (1582-1664) of the Ming-Qing dynastic transition. It breaks new grounds in Qian Qianyi studies and Qing poetry studies. The book is based on meticulous research, attention to detail, and careful close-readings of the related poems and texts, therefore the discussions are well-grounded, balanced, and comprehensive. “The Sickbed Poems” by Qian are of great literary and biographical values, and this is the first book to offer a comprehensive and exhaustive interpretation of the poem series. Not only is the methodology adopted in this book useful for studying Qian Qianyi’s poetry, it also has larger implications for classical Chinese poetry studies. Readers who are methodology- and theory- minded will find the book particularly appealing.
This book studies the last poem series, “The Sickbed Poems,” of the great scholar-poet Qian Qianyi (1582-1664) of the Ming-Qing dynastic transition. It breaks new grounds in Qian Qianyi studies and Qing poetry studies. The book is based on meticulous research, attention to detail, and careful close-readings of the related poems and texts, therefore the discussions are well-grounded, balanced, and comprehensive. “The Sickbed Poems” by Qian are of great literary and biographical values, and this is the first book to offer a comprehensive and exhaustive interpretation of the poem series. Qian Qianyi witnessed the dynastic transition from the Ming to the Qing. Qian flourished in the late Ming as a pre-eminent poet, scholar, and an aspiring court official; in the latter, he suffered many difficulties and frustration. At the fall of the Ming, Qian surrendered to the conquering Qing. His change of loyalty to the Qing earned him the infamous appellation of “twice-serving official” in history. Yet, political infamy does not affect Qian’s status as a master poet of late imperial China. Entitled “Forty-six Miscellaneous Poems to Dispel Cold on My Sickbed,” the poem series was written on and off during Qian’s last few living months. True to its title, the poems are embedded with images of old age, sickness, and cold weather. More importantly, reflections on life, friends, and momentous events of the past infuse the poems, the poem series might be seen as a book of memory and witnessing. This book begins with an introduction to the state of the art of Qian Qianyi studies. Qian was a controversial historical figure, so much so that past studies of Qian has been predominantly historical (and moralistic), rather than literary, in nature. This approach overlooks the fact
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Book cover of Qian Qianyi “Bingta xiaohan zayong” Lunxi.
that Qian’s immortality is assured by the quality of his works, not by the results of his deeds in history; and sure enough, moral criticism does not do justice to art. The author of this book urges for a literary turn in Qian Qianyi studies.
A portrait of Qian Qianyi, from Qingdai xuezhe xiangzhuan .
The book proper is divided into two parts. Part I addresses the following issues: Qian Qianyi was undoubtedly a politically ambitious person, whereas his poetic aspirations were divine, too. What is the relationship between poetry, as a literary practice, and Qian’s political involvements? When Qian started writing his "Sickbed Poems," he was over eighty years old, his health failing rapidly. What is the meaning of writing poetry on life's end, particularly at the time of cold and darkness? Qian composed a "self-preface" to his collection of "Sickbed Poems," in which he jested about the humble ambition in writing these poems and apologized for their vulgar style. Nevertheless, Qian's "Sickbed Poems" are arguably among the best poems he had ever written. What is the self-image that Qian desired to leave behind to posterity? Qian was a controversial figure of the Ming-Qing dynastic transition; he lived a life full of adventures and events. Written on the last leg of his life's journey, these forty-six poems are filled with memories, reflections, and introspection. What will we see when we glimpse into the past memories and inner thoughts of the dying Qian? And after all, what are the literary values of these "miscellaneous" poems? Part II of this study provides extensive commentaries on each of these forty-six poems. Qian's poems are known for their lyrical intensity and relentless allusiveness—they are no easy read. Preparing the annotations and commentaries was painstaking and difficult, but it was a labor of love on the part of the author. Part II of this book is intended to make reading Qian's poetry more accessible and enjoyable for the readers. Not only is the methodology adopted in this book useful for studying Qian Qianyi's poetry, it also has larger implications for classical Chinese poetry studies. Readers who are methodology- and theory-minded will find the book particularly appealing. Poem #46 of “The Sickbed Poems,” written in Qian Qianyi’s calligraphy (in the collection of Shanghai Museum).
▍Publication Taipei: Academia Sinica & Linking Publishing Company (Academia Sinica series), 432 pages, 2012.
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Division of the Humanities and Social Sciences
After Empire: The Conceptual Transformation of the Chinese State, 1885-1924 Peter Zarrow Institute of Modern History, Academia Sinica, Taiwan
Abstract
This book begins with the question: how was it that Chinese people stopped believing in the emperor and imagined a radically new political system? From 1885 to 1924 China underwent a period of acute political struggle and cultural change. After two thousand years of monarchical rule, Confucian political orthodoxy collapsed. The modern Chinese idea of the state was forged in four decades of struggle among competing definitions of citizenship, national identity, and republicanism. In just two generations, Chinese elites and commoners moved from a belief in the cosmic and charismatic role of the emperor to deepseated skepticism. The traditional emperorship had affirmed moral values held by the whole community; the collapse of the monarchy was therefore a significant part of widespread cultural crisis. The whole cultural edifice of the imperial system declined together, including, first, the coercive powers of the imperial court vis-à-vis local society; second, the civil service examination system; and third, the immense system of classical learning upon which the exams were based. New and various republican ideologies were then constructed in a series of political experiments across the twentieth century.
Perhaps Kang Youwei's essays of the mid-1880s were the first writings to fundamentally challenge the traditional monarchical system. These essays, using a range of Chinese and Western intellectual resources, made a case for statism and offered a vision of citizenship that later writers and revolutionaries expanded upon. Kang Youwei's writings were the beginning of a radical reform movement. These essays were based on Kang’s unique understanding of New Text Confucianism, combined with a theory of linear progress. Kang's ideas formed the basis of the 1898 Reform Movement. From this starting point, Liang Qichao familiarized himself with Western and Japanese political theory. He then developed a new theory of Chinese citizenship after the turn of the twentieth century. Citizenship, for Liang, was rooted in both national identity on the one hand, and civic virtue and political participation on the other. Liang's view of the state was ultimately based on the concept of sovereignty. "Sovereignty"-a concept new to late Qing elites—came into widespread use through legal writings and international law. Also important was the notion of the "organic state". That is to say, that the state was more than a chance assemblage of people, more than simply a government: it was a human-constructed entity with is own will (意志) and practice (行動). Another prominent radical, Cai Yuanpei, compared the state to a company: citizens were shareholders who chose
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the managers. The theocratic basis of the empire had disappeared from political discussion. That the concept of the state had been secularized was made clear by the brief resurgence of reactionary thought at the end of the 1890s. Statesmen such as Zhang Zhidong and critics of the 1898 Reform Movement feared that the radical reformers wanted to abolish the Three Bonds of Confucian morality. Though not opposed to all reform, they thought any attack on the absolutist monarchy represented an attack on China's familial and social structure. They defeated the 1898 Reform Movement, but their arguments failed. In the wake of the disaster of the Boxer uprising, the Qing court itself began to promote radical reforms-a constitution, a parliament, a new judiciary system, and universal male education. Meanwhile, the revolutionary storm was gathering energy. Based on a strong sense of the injustice of minority Manchu rule over the Han nation, revolutionaries envisioned a republic based on ethnic citizenship. Anti-Manchuism stemmed from identification with the victims of the Manchu invasion of the seventeenth century. Revolutionaries such as Zhang Binglin and Liu Shipei sought to rewrite Chinese history as the story of the rise of the Han nation. Nonetheless, their ideas owed a great deal to the reformers such as Liang Qichao. Revolutionary theories of republicanism, human rights, and socialism had all been anticipated in the earlier Reform Movement. With the success of
the 1911 Revolution, however, the new leaders of the Republic of China turned back to the idea of a multinational state. New rituals of state like Double Ten Day symbolized the new Republic's claims to legitimacy. On the one hand, the Republic was unstable. Yuan Shikai's attempt to found a new monarchy, like his worship of Heaven, demonstrates how conservative political leaders were. On the other hand, the failure of Yuan's monarchical movement proved that the 1911 Revolution was irreversible. Even conservatives who promoted Confucianism acknowledged the legitimacy of republicanism and now argued that Confucianism and
republicanism were compatible. In 1924 the last Qing emperor was expelled from the Forbidden City. The creation of the Republic of China in 1912, whatever its flaws, marked the establishment of modern Chinese national identity. We can see this in the use of the terms "Chinese" and "citizen" and loyalty to the nation-state. What different groups agreed on in the early twentieth century was the importance of the state. Attempts to rebuild the normative and legal foundations of China from the bottom up led to the secularization of sovereignty.
▍Publication Stanford: Stanford University Press, 395 pages, 2012.
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Division of the Humanities and Social Sciences
WTO and the Greater China: Economic Integration and Dispute Resolution Chien-Huei Wu Institute of European and American Studies, Acadmia Sinica, Taiwan
Abstract
This book illustrates how the constitutional feature of the WTO – allowing separate customs territories to become a Member – brings about the coexistence of China, Taiwan, Hong Kong and Macau in the WTO. It examines the economic integration and the dispute settlement systems within Greater China. It explores their interactions within the multilateral WTO framework, their practices under the new genre of FTA, and their policies in adopting trade defence measures against each other. This book offers a good case study on the impact of WTO membership upon domestic reform and how it contributes to regional integration. It also provides a comprehensive analysis on the existing provisions in the WTO agreements pertaining to judicial review.
The constitutional feature of the World Trade Organisation (the WTO) - that it does not limit its membership to sovereign states - allows Taiwan, albeit as a separate customs territory, to accede to it and thus creates an unusual legal landscape in the international trading system, where both Taiwan and China enjoy full membership. This peculiarity is further intensified when China’s two separate-customs-territory Members – Hong Kong, China and Macau, China – are added to the picture. The interactions among the four WTO Members of China, Taiwan, Hong Kong, China and Macau, China are unique. As Hong Kong and Macau became Contracting Parties to the General Agreement on Tariffs and Trade through the sponsorship of the United Kingdom in 1986 and of Portugal in 1991 respectively and participated in and accepted the result of the Uruguay Round negotiations, they are among the founding Members of the WTO when this new organisation came into being in 1995. China and Taiwan acceded to the WTO at the Doha Ministerial Conference, where China’s accession process was finalised on 10 November 2001 and Taiwan’s one day later. Consequently, China became the 143rd Member of the WTO on 11 December 2001, while Taiwan, as a separate customs territory became the 144th Member on 1 January 2002. In view of this unique legal landscape within the WTO, this work thus aims to examine the integration of the Greater China and interaction between these four Members at different fora: multilaterally; bilaterally or domestically. It also locates the subject matter in a broader context where the role of judges in external trade will be explored. It will use the interactions between these four WTO Members as an example to illustrate how dispute resolution mechanisms at different fora contribute to judicial settlement in trade disputes.
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This work stresses the importance of the WTO disciplines in regulating these integration processes and the role of dispute settlement mechanism in resolving trade disputes arising therefrom. This work argues that effective judicial review can help to ensure rational decision-making in foreign trade relations. It also helps to preserve the economic autonomy of Hong Kong and Macau. Besides, effective judicial review ensures the compliance to the WTO rules both in Taiwan and in China. In addition, an independent and impartial judicial review is an essential vehicle to protect the right to trade as prescribed in China’s Accession Protocol. Above all, the WTO Dispute Settlement Mechanism is crucial in resolving trade disputes between the four WTO members of the Greater China. Judicial governance in the foreign trade relations is thus indispensible. A well-functioning dispute settlement mechanism is a central element for the economic integration in the Greater China that eventually contributes to their mutual understanding and mutual trust. This work argues that the WTO constitutionalism may contribute to judicial settlement of trade disputes arising from these legal and economic integration processes. WTO membership may be perceived as a pre-commitment to the four WTO Members of the Greater China. The WTO accession is a pre-commitment to China for widening and deepening economic and legal reforms, and thus for promotion of rule of law in China. The WTO accession is a pre-commitment to Taiwan for the progressive liberalisation of cross-strait trade in order to enhance economic and legal integration, to contribute to mutual understanding, and therefore, to ensure peace and security across the Taiwan Strait. The WTO memberships of Hong Kong, China and Macau, China are also pre-commitments of these two separatecustoms-territory Members for them to observe free
trade rules/policies and thus to maintain their economic autonomy. Their memberships are also China’s precommitments to these two SARs in relation to their legal and economic autonomy to participate in the international trading system. Secondly, the right to trade prescribed in China’s accession protocol, free-port status and free trade policies dictated by the HKBL and the MABL together effective judicial review may gradual sustain a constitutionalism in its minimum form. Through the lens of third party participation, this work finds that Taiwan tends to participate as a third party in complaints brought about by/against China. Taiwan may stand in line with China; it may argue against China; it may also act as a passive observer without making clear its position. China has also participated in the complaint brought about by Taiwan, namely, the EC – IT Products , where China takes the same position as Taiwan does as China has the same trade interests on information technology products into the EU’s market. This work also explores the dispute settlement mechanisms provided by the ECFA and other bilateral agreements concluded between Taiwan and China. This work finds that the dispute settlement mechanisms are rather primitive and diplomatic in nature, which is insufficient to safeguard the rights and obligations of both Parties and to provide security and predictability for individual economic actors therein. This work also analyses trade defence measures imposed by Taiwan and China against each other and explores the effectiveness of domestic judicial review on these trade defence measures. It finds that only limited affected parties resort to domestic judicial review which offers little protection. Regarding dispute resolution between China and Hong Kong and Macau, this work approach this issue under two frameworks: the constitutional/national law framework and the WTO/CEPA framework. Under the constitutional/national law framework, this work examines vertical and horizontal interaction between China and its two SARs. Emphasis is actually placed on the interaction between the NPCSC and the CFI of the HKSAR. This work sees a danger of undermining the legal and economic autonomy of the two SARs by the NPCSC through the interpretation of the two Basic Laws. Under the WTO/CEPA framework, this work briefly recalls the trade policy and practice of Hong Kong and Macau in the GATT and WTO. It then explores the nature of the CEPA under the WTO rules and examines existent trade dispute mechanisms in both the WTO and the CEPAs. This work argues that it is unlikely that China, Hong Kong or Macau to refer to the WTO Dispute Settlement Mechanism. At the same time, the dispute settlement mechanism as set out for in the two CEPAs does not offer adequate judicial protection as well. Whereas the preference of China, Hong Kong and Macau not to internationalise or judicialised their trade disputes, such approach may prejudice the rights and
interests of individual economic actors. With respect to dispute resolution between Taiwan and Hong Kong and Macau, this work finds the same tendency not to refer to the WTO Dispute Settlement Mechanism. It also illustrates how China may affect policy making or trade negotiation between Taiwan and Hong Kong and Macau. It argues that private parties prefer to refer to domestic courts and arbitral procedures to resolve their disputes given the attitude of their governments to avoid intergovernmental confrontation. After examining domestic legal framework and jurisprudence in relation to the mutual recognition of arbitration awards and civil judgments, this work finds that the ideas of ‘sovereign interests’‘national security’, and‘public order’play a key role in granting their recognition and enforcement. T h e w a y a h e a d o f t h e f o u r W TO M e m b e r s of the Greater China would be closer economic interdependence. But the persisting question remains: can the institution sustain such interdependence? So far, Taiwan and China has concluded the ECFA and a number of bilateral agreements. China has also concluded the CEPAs and seven supplements with Hong Kong and Macau. Spurred by the ECFA, Hong Kong and Macau may soon conclude a bilateral agreement with Taiwan. These bilateral agreements would contribute to legal and economic integration in the Greater China, but at the same time bring about numerous disputes. The WTO discipline and the scrutiny of the CRTA should come into play with a view to ensure these bilateral agreements WTO-compatible. Dispute settlement mechanisms provided in these bilateral agreements need to evolve so as to provide effective judicial protection both for the Parties and those individual economic actors in the Greater China. Domestic courts are strongly encouraged to review external trade measures and protect rights and interests of private parties. They should also ensure the faithful implementation of WTO rules in the Greater China. Above all, the WTO Dispute Settlement Mechanism has to remain intact should the four WTO Members of the Greater China decide to avail of this mechanism. It is the key to ensure that China would implement its WTO obligation to‘provide an independent and impartial judicial review’.
▍Publication Leiden, Boston: Martinus Nijhoff, 308 pages, 2012.
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Division of the Humanities and Social Sciences
The Psychological Well-being of East Asian Youth Chin-Chun Yi Institute of Sociology, Academia Sinica, Taiwan
Abstract
This book provides readers with a comprehensive picture of diverse growth trajectories of East Asian youth from early adolescence to young adulthood. Based on a unique panel dataset of Taiwan Youth Project (TYP), various life experiences since the junior high to senior high and to college are analyzed with a special effort to delineate influences from the immediate social context on the developmental outcome of psychological well-being. Situated in a rapidly changing social context, a typical youth in this region is faced with the tension between tradition and modernity. This book aims to explore significant social mechanisms affecting different growth patterns and to delineate the interplay of family, school, peers and community in the developmental process of East Asian youth during this particular life course.
Given the structural context of East Asia, in which educational achievement and a close bond between generations are strongly emphasized, growing up in the contemporary society is certainly not easy for youth in this region. In this book, we argue that the tension between tradition and modernity has become much more acute for youth in East Asia because of the overwhelming effect of globalization. We also argue that East Asian adolescents experience both greater social constraints from patriarchal values as well as greater social support from family and kin than their counterparts in other regions. Hence, this book aims to show how adolescents in East Asia react and adapt to current social situations and to delineate the relative importance of various mechanisms accounted for the diversified growth patterns. In order to unravel this complex process, the time frame is set from early adolescence to young adulthood. We take a broad definition of the psychological wellbeing which includes depressive symptoms, happiness, self-esteem, family cohesion, deviant or problem behaviours, and sexual permissiveness. While most chapters based analyses on the Taiwan Youth Project, a longitudinal panel data, they are used to illustrate East Asian youth in general due to the relatively homogenous cultural heritage. Our basic stand is that individual psychological well-being represents the final outcome of the developmental process during this important transitional life course. The book starts with chapters on the family context. Growing up in a patrilineal society in which traditional family values and intergenerational practices being relatively well preserved, East Asian youth are inevitably bound by the conventional practices and normative expectations. We propose that “Guan” with its cultural legitimacy is a better parenting concept in studying Chinese families. The emergence of single-parent
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families reveals different social meanings between divorce and widowhood with the former producing poorer psychological well-being among adolescent children. Findings on the prevalent co-residence experience with grandparents in Taiwan and in East Asia point out that grandparents are considered family members (not kin), but they can not replace parents for the growth outcome of adolescents.
Throughout the book, it is contended that for a typical East Asian adolescent, mental health is closely linked to and intertwined with the educational performance. The value of attaining the highest educational achievements accompanied by the strong family expectations on educational success has conditioned and dominated the life experiences of adolescents in East Asia. For chapters on the school context, this unique aspect is captured by the classroom effect in the middle school, a conventional practice in the region. The classroom effect is examined on the deviant behaviors as well as on friendship network formation and their relatedness to academic performance. Furthermore, the unique cram schooling in East Asia, as a necessary product of the entrance examination competition, receives special attention and social class implication is discussed in the text. The last section of the book focuses on entering into adulthood. Our analysis shows two peaks of depressive symptoms, corresponding to the timing of the senior high and college entrance examinations, and confirms the tracking effects. For other significant issues pertaining to this transitional period, such as the experience of occupational acquisition, the formation of intimate relationships and the decision of leaving home, our analyses clearly indicate that unconventional patterns are emerging in that a substantial proportion of young adults are idle at home, engaging in pre-marital sex and delayed home leaving. We also show that youth who deviates from normal social expectations have generally lower psychological well-being.
This book ends with three chapters from other East Asian societies. The comparative perspective clearly demonstrates similar challenges faced by contemporary youth in East Asia. The conclusion drawn from the book is that adapting to or succeeding in educational competition is perhaps the most significant life experience shared by East Asian youth during this particular life course. Our overall findings confirm that the dominant social value placed on educational achievement both constrains and supports adolescent’s individual well-being. Those who attain the socially prescribed goal and those who fail often demonstrate diversified growth trajectories before entering adulthood. We hope this book will enable readers to reflect and contemplate the potential future development of the affluent generation in East Asia.
▍Publication Dordrecht: Springer Publishing Co., 345 pages, 2012.
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2012 Significant Research Achievements of Academia Sinica
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Abstracts of Other Significant Publications
Super Duality for General Linear Lie Superalgebras and Applications Proceedings of Symposia in Pure Mathematics, American Mathematical Society 86 (2012): 113-136.
Shun-Jen Cheng, Ngau Lam, and Weiqiang Wang Institute of Mathematics, Academia Sinica
In recent years our main effort has been the study of the relationship between the representation theory of Lie algebras and that of Lie superalgebra. In 2012, in a joint work with Weiqaing Wang and Ngau Lam, we generalized the notion of super duality to type A Lie algebra and type A Lie superalgebra under rather general assumptions. As a consequence, we give a solution to the irreducible character problem for modules over the Lie superalgebra gl (n|2) in the full BGG category.
Entropy-driven Single Molecule Tug-of-war of DNA at Micro-nanofluidic Interfaces Nano Letters 12 (2012): 1597–1602.
(Research Highlights, Nature 2012, 482, 442)
Jia-Wei Yeh, Alessandro Taloni, Yeng-Long Chen, and Chia-Fu Chou Institute of Physics, Academia Sinica
Entropy-driven polymer dynamics at the nanoscale is fundamentally important in biological systems but the dependence of the entropic force on the nanoconfinement remains elusive. Here we established an entropy-driven single molecule tug-of-war (TOW) at two micro-nanofluidic interfaces bridged by a nanoslit, performed the force analysis from a modified worm-like chain in the TOW scenario and the entropic recoiling process, and determined the associated scalings on the nanoconfinement. Our results provide direct experimental evidence that the entropic forces in these two regimes, though unequal, are essentially constant at defined slit heights, irrespective of the slit lengths and the DNA segments within. Our findings have the implications to polymer transport at the nanoscale, device design for single molecule analysis, and biotechnological applications.
Single molecule tug-of-war and the entropic recoiling of DNA at micro-nanofluidic interfaces: (a) tug-of-war, (b) retraction recoiling, (c) experimental setup, and (d-i) fluorescence images of the process.
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Field-induced Expansion Deformation Effect in Metallic Films Physical Review Letters 108 (2012): 146102.
W. Y. Chan, H. S. Huang, W. B. Su, W. H. Lin, H. T. Jeng, M. K. Wu, and C. S. Chang Institute of Physics, Academia Sinica
We use scanning tunneling microscopy and spectroscopy to study the energy shift of quantum well states in metallic film. It is found that, with an increase of the electric field, the behavior of the energy shift can be grouped into two different modes for most QW states. In the first mode, the state energy moves toward high energy monotonically. In the second mode, the state energy shifts to a lower energy initially and then turns around to a higher energy. Moreover, we have observed that the QW states of higher energy behave in preference to the first mode, but they gradually change to the second mode as the Pb island becomes thicker. This thickness-dependent behavior reflects that the surface atoms can be displaced outward by the electric field, which can subsequently induce the movement of atoms in the film to establish an expansion deformation. And the expansion is proportional to the film thickness. This finding opens up a possibility to measure the Young’s modulus of metallic film in the nanometer scale.
BODIPY Dyes with β -conjugation and their Applications for High-efficiency Inverted Small Molecule Solar Cells Chemical Communications 48 (2012): 8913-8915.
Hsin-Yu Lin, Wei-Ching Huang, Yung-Chung Chen, Hsien-Hsin Chou, Chih-Yu Hsu, Jiann T. Lin, and Hao-Wu Lin Institute of Chemistry, Academia Sinica
New BODIPY dyes with conjugated arylamine at two β -sites have been synthesized. Prominent charge-transfer from the peripheral amine to the BODIPY core results in a large Stokes shift in the emission spectra of the compounds. Small molecule BODIPY dyes incorporating conjugated substituents at the β sites have been synthesized. Solution processed inverted bulk heterojunction cells were fabricated from the blends of the dyes and PC71BM. The cells exhibited very high opencircuit voltages (>0.9 V) and a high conversion efficiency of 3.22% has been achieved.
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Abstracts of Other Significant Publications
Regulation of Mammalian Transcription by Gdown1 through a Novel Steric Crosstalk Revealed by Cryo-EM EMBO Journal 31
(2012): 3575-3587.
Yi-Min Wu, Jen-Wei Chang, Yen-Chen Lin, Chun-Hsiung Wang, Pei-Lun Wu, Shih-Hsin Huang, Chia-Chi Chang, Xiaopeng Hu, Averell Gnatt, and Wei-Hau Chang Institute of Chemistry, Academia Sinica
In mammals, a distinct RNA polymerase II form, RNAPII(G) contains a novel subunit Gdown1 (encoded by POLR2M), which represses gene activation, only to be reversed by the multisubunit Mediator co-activator. Here,we employed single-particle cryo-electron microscopy (cryo-EM) to disclose the architectures of RNAPII(G), RNAPII and RNAPII in complex with the transcription initiation factor TFIIF, all to ~19 Angstrom. Difference analysis mapped Gdown1 mostly to the RNAPII Rpb5 shelf-Rpb1 jaw, supported by antibody labeling experiments. These structural features correlate with the moderate increase in the efficiency of RNA chain elongation by RNAP II(G). In addition, our updated RNAPII–TFIIF map showed that TFIIF tethers multiple regions surrounding the DNA-binding cleft, in agreement with cross-linking and biochemical mapping. Gdown1’s binding sites overlap extensively with those of TFIIF, with Gdown1 sterically excluding TFIIF from RNAPII, herein demonstrated by competition assays using size exclusion chromatography. In summary, our work establishes a structural basis for Gdown1 impeding initiation at promoters, by obstruction of TFIIF, accounting for an additional dependent role of Mediator in activated transcription. ➊ The cryo-EM structure of mammal RNA
polymerase II (RNAPII) and the regions where both Gdown1 and TFIIF bind to RNAPII.
❷ Size exclusion chromatography reveals
Gdown1 can displace TFIIF on RNAPII but not the other way around.
➌A proposed model to explain how Gdown1
may repress transcription by “blocking the formation of the initiation complex” , a process to be reversed by the Mediator protein.
Age and Geochemical Characteristics Of Paleogene Basalts Drilled from Western Taiwan : Records of Initial Rifting at the SE Eurasian Continental Margin Lithos 155 (2013): 426-441.
Kuo-Lung Wang, Sun-Lin Chung, Y.-M. Lo, Ching-Hua Lo, Huai-Jen Yang, R. Shinjo, Tung-Yi Lee, Jong-Chang Wu, and Shiuh-Tsann Huang Institute of Earth Sciences, Academia Sinica
The southeastern Eurasian continental margin has been characterized by formation of rift basins associated with intraplate basaltic volcanism since early Cenozoic time. To better understand the tectonomagmatic evolution, in particular the initial rifting record, this study reports new age, major- and trace-elemental, and Sr-Nd-Pb isotope data of volcanic rocks drilled in the western coast of Taiwan, Taiwan Strait and on the Penghu Islands including outcrop on the Huahsu islet, revealing an older episode of Eocene (~56-38 Ma) intraplate magmatism prior to the widespread Micoene (~23-9 Ma) volcanism on Penghu Islands, Kuanhsi-Chutung and Kungkuan areas for the first time. The Eocene bimodal volcanism entails a transition from the latest Cretaceous magmatism in the western Taiwan Strait that not only signals incipient rifting in the region, but also provides the key tectonomagmatic link between the latest Cretaceous subduction-related rocks and the Miocene intraplate rocks.
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Online Optimization with Gradual Variations Journal of Machine Learning Research Proceedings Track 23 (COLT) (2012): 6.1-6.20.
Chao-Kai Chiang, Tianbao Yang, Chia-Jung Lee, Mehrdad Mahdavi, Chi-Jen Lu, Rong Jin, and Shenghuo Zhu Institute of Information Science, Academia Sinica
Many situations in daily life require ones to make repeated decisions in an unknown and changing environment, including examples such as trading stocks, forecasting weather, commuting to work, playing games, etc. This motivates the study of the so-called online optimization problem in which a player must iteratively choose an action and receive a loss for a number of rounds. We consider a natural restriction of this problem in which the loss functions have a small deviation, to model environments which evolve gradually. For this, we provide online algorithms which achieve smaller regret bounds than previous ones.
Image Feature Extraction in Encrypted Domain with Privacy-preserving SIFT IEEE Transactions on Image Processing 21 (2012): 4593-4607.
Chao-Yung Hsu, Chun-Shien Lu, and Soo-Chang Pei Institute of Information Science, Academia Sinica
Privacy has received considerable attention but is still largely ignored in the multimedia community. Consider a cloud computing scenario where the server is resource-abundant, and is capable of finishing the designated tasks. It is envisioned that secure media applications with privacy preservation will be treated seriously. In view of the fact that scale-invariant feature transform (SIFT) has been widely adopted in various fields, this paper is the first to target the importance of privacy-preserving SIFT (PPSIFT) and to address the problem of secure SIFT feature extraction and representation in the encrypted domain. As all of the operations in SIFT must be moved to the encrypted domain, we propose a privacy-preserving realization of the SIFT method based on homomorphic encryption. We show through the security analysis based on the discrete logarithm problem and RSA that PPSIFT is secure against ciphertext only attack and known plaintext attack.
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Abstracts of Other Significant Publications
Dynamical Functional Prediction and Classification, with Application to Traffic Flow Prediction The Annals of Applied Statistics 6 (2012): 1588-1614.
Jeng-Min Chiou Institute of Statistical Science, Academia Sinica
Motivated by the need for accurate traffic flow prediction in an intelligent transportation system, we propose a functional data method to analyze traffic flow patterns and predict the future traffic flow for an up-to-date and partially observed flow trajectory. We approach the problem by sampling traffic flow trajectories from a mixture of stochastic processes, each reflecting a distinct pattern of daily traffic flow trajectories. The functional mixture prediction approach combines functional prediction with probabilistic functional classification to take distinct traffic flow patterns into account. The method not only assist in predicting traffic flow trajectories, but also identify distinct patterns in daily traffic flow of typical temporal trends and variabilities, which successfully improves the prediction accuracy in daily traffic flow rates. Although motivated by traffic flow analysis and prediction, the proposed methodology is widely applicable in analysis and prediction of longitudinally recorded functional data.
Pretreatment Epidermal Growth Factor Receptor (EGFR) T790M Mutation Predicts Shorter EGFR Tyrosine Kinase Inhibitor Response Duration in Patients with Non-small-cell Lung Cancer Journal of Clinical Oncology 30 (2012): 433-440.
Kang-Yi Su, Hsuan-Yu Chen, Ker-Chau Li, Min-Liang Kuo, James Chih-Hsin Yang, Wing-Kai Chan, Bing-Ching Ho, Gee-Chen Chang, Jin-Yuan Shih, Sung-Liang Yu, and Pan-Chyr Yang Institute of Statistical Science, Academia Sinica
Inhibition of EGFR kinase activities by EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib results in effective treatment for patients with NSCLC. However, not every patient has benefit for receiving target therapy. In addition, the efficacy of target therapy will be reduced in NSCLC patients due to drug resistance. EGFR-activating mutations in exon 19 and exon 21 that correlated with a high TKIs treatment response rate and prolonged progression-free survival have been identified. Therefore, establishment of the platform for gene testing to select patients with EGFR mutations is necessary in worldwide clinical lung cancer management especially in East Asia and Taiwan with the EGFR mutation rate as high as 50%. To achieve this aim, we utilized nucleotide mass spectrometry to set up EGFR mutation detection platform with high sensitivity and high specificity. This platform not only has high detection limitation to identify mutation frequency as low as 1% among wild-type background but also selects patients with benefit for target therapy 30% more than traditional EGFR mutation detection system. Furthermore, we also find that T790M resistant mutation may occur before drug administration. This leads us to pay more attention on patients with pretreatment T790M mutation in following clinical care. This study provides a gene test method not only for lung cancer but also for other disease required translational personalized medicine.
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Growth of Large-area and Highly Crystalline MoS2 Thin Layers on Insulating Substrates Nano Letters 12 (2012): 1538-1544.
K. K. Liu, W. Zhang, Y. H. Lee, Y. C. Lin, M. T. Chang, C. Y. Su, C. S. Chang, H. Li, Y. Shi, H. Zhang, C. S. Lai, and L. J. Li Institute of Atomic and Molecular Sciences, Academia Sinica
Recently, the inorganic layered transition-metal dichalcogenide (LTMDs) such as MoS2 and WS2 have drawn great attention due to their low cost, high chemical stability, excellent photocatalytic/electrocatalytic properties and possibility for valleytronics. Their properties can be tailored by their crystal structure, layer thickness and surface modifications for the applications such as flexible electronics, optoelectronics and energy storage. Only mechanically exfoliated or solution exfoliated LTMDs are available in literature. We have successfully synthesized thin layer MoS2 by chemical vapor deposition (CVD). The transistor devices obtained exhibit n-type behaviors with the on/off current ratio ~105 and field-effect electron mobility up to 6 cm2/Vs. These CVD MoS2 transistors exhibited remarkably high mechanical flexibility and no degradation in electrical characteristics was observed w h e n t h e y w e re h i g h l y b e n d e d to a curvature radius of 0.75 mm. We anticipate that MoS 2 layer may become a competitor of conducting p o l y m e r s i n f l e x i b l e e l e c t ro n i c applications.
Vitalizing Fuel Cells with a Vitamin: Pyrolyzed Vitamin B12 as Nonprecious Catalyst for Enhanced Oxygen Reduction Reaction Energy & Environmental Science 5 (2012): 5305-5314.
S. T. Chang, C. H. Wang, H. Y. Du, H. C. Hsu, C. M. Kang, C. C. Chen, C. S. Wu, S. C. Yen, W. F. Huang , L. C. Chen, M. C. Lin, and K. H. Chen Institute of Atomic and Molecular Sciences, Academia Sinica
The limited natural abundance and high cost of Pt has been a major barrier in its applications for hydrogen fuel cells. In this work, based on the pyrolyzed vitamin B12 (py-B12/ C), it is reported to produce superior catalytic activity in the oxygen reduction reaction (ORR) with an electron transfer number of 3.90, which is very close to the ideal case of 4. The H2–O2 fuel cell using py-B12/C provides a maximum power density of 370 mW/cm 2 and a current density of 0.720 A/cm 2 at 0.5 V at 70 oC. The long-term stability and high ORR activity of py-B12/C make it a viable candidate as a Ptsubstitute in the ORR.
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Abstracts of Other Significant Publications
A New Method for Magnetic Field Strength Maps for Molecular Clouds The Astrophysical Journal 747 (2012): 79.
Patrick M. Koch, Ya-Wen Tang, and Paul T.P. Ho Institute of Astronomy and Astrophysics, Academia Sinica
This paper reports on a new method to measure the strength of magnetic fields in molecular clouds, where stars are being formed. Understanding the details of star formation has been a challenge for decades. Magnetic fields are thought to play a key role in this process. Measuring the field strength is, thus, paramount to make quantitative assessments. Commonly used observational techniques provide either only one single averaged field strength for an entire star forming region, or they provide only isolated values (e.g. Zeeman observations). In all cases, valuable information is lost as the role of the field changes with location within a molecular cloud. In this work, we use dust polarization observations from the Submillimeter Array (SMA) at radio frequencies around 345 GHz for position-dependent estimates of the field strength. Dust particles couple to the field which is why coherent polarized emission can be detected. From the polarized emission we then derive the orientation of the magnetic field. Our method uses these field orientations in combination with changes (gradients) in dust densities. The geometry of these morphological features is then linked to magnetohydrodynamics equations, so that the field strength can be calculated. In this way, we are, for the first time, able to derive a field strength at every location where polarization is detected. Applied to the SMA observation of the W51 e2 core with a resolution of 0.7 arcsec, we find an increase in field strength from about 1 mG in the outer parts to about 10 mG in the center. Additionally, our method yields a model-independent force ratio which quantifies how effectively the field tension force withstands gravity. For W51 e2, we find that the field increases the collapse time by a factor of about 10, making the magnetic field a promising candidate to explain the observed low star formation efficiencies. Upper Figure: SMA dust continuum observation at 345 GHz of the star-forming core W51 e2 with a resolution of about 0.7 arcsec. The color-wedge indicates the dust emission intensity. The measured magnetic field morphology (white segments) shows that gravity is bending the field lines almost radially and pulling them toward the core center. Overlaid in blue are the intensity gradients of the dust emission. The correlation between field and intensity gradient orientations is used as a starting point in our method. Lower Figure: Resulting field strength map for W51 e2. An increase in field strength toward the center is apparent.
Discovery of the Youngest Intermediate-mass Protostar and Substructures within Their Massive Envelope The Astrophysical Journal 752 (2012): 10.
Satoko Takahashi, Kazuya Sigo, Paul T. P. Ho, and Kengo Tomida Institute of Astronomy and Astrophysics, Academia Sinica
Young stars form via gravitational collapse within cold (10 K) and dense (nH2=104 cm-3) molecular cores. Hence, studying parental molecular core is crucial to understand the earliest stage of the star formation process Using the Submillimeter Array (SMA), we discovered the youngest intermediate-mass protostellar core ever found (<104yr; upper figure) in the Orion star forming region. Density structure of the observed core was directly compared to theoretically predicted molecular cores in different evolutionary stage such as prestellar core, first adiabatic core, and protostellar core (bottom figure). The result clearly shows that a self-luminous source (i.e., protostar) is necessary to explain the observed high flux density. This implies that the source is likely a protostellar core at the earliest evolutionary stage. In addition, we spatially resolved substructures within the circumstellar envelope/disk in this early evolutionary stage (denoted by numbers in the upper figure). Each substructure has brown dwarf mass and their separation suggests that thermal fragmentation might occur within the envelope/disks. This could be related to the brown dwarf/planet formation around the primary star as theoretically predicted in recent studies. The density structure analysis would be one of the most promising ways to study protoplanetary systems, and paves the way for more sensitive and detailed studies in the era of large aperture millimeter/submillimeter radio interferometers such as ALMA. (http://www.almaobservatory.org/). Upper figure: Contours represents the intensity of the 850 micron continuum emission. Highest angular resolution achieved with the SMA observations has revealed detailed spatial structures within a massive protostellar envelope. Spatially resolved substructures are denoted by number 1-7. Bottom figure: Density structure analysis using the visibility amplitude plot (i.e., directly measure values from the SMA observations). The signal and noise levels are denoted by open circles and horizontal lines, respectively. The theoretically expected models were denoted by blue (prestellar core), green (the first adiabatic core), and red (protostar+ circumstellar disk/envelope), respectively.
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The Taiwan ECDFS Near-infrared Survey : Very Bright End of the Luminosity Function at z>7 The Astrophysical Journal 749 (2012): 88.
Bau-Ching Hsieh, Wei-Hao Wang, Haojing Yan, Lihwai Lin, Hiroshi Karoji, Jeremy Lim, Paul T. P. Ho, and Chao-Wei Tsai Institute of Astronomy and Astrophysics, Academia Sinica
The Taiwan ECDFS Near-Infrared Survey (TENIS) images the Extended Chandra Deep Field-South (ECDFS) with Canada-France-Hawaii Telescope Wide-field InfraRed Camera at J (1.2 μm) and Ks (2.2 μm) bands. One of our early science results is the selection of bright distant galaxies using the Lymanbreak technique, which identifies the strong high-redshift inter-galactic medium absorption shortward to the Lyman-alpha wavelength that produces a steep color break (or dropout) between two adjacent filter bands. For galaxies at redshift between 7 and 9, this is the z' (0.85 μm)-J color break (or z' -dropout). After carefully examining our sample, we found an excellent luminous z' -dropout candidate, TENIS-ZD1. TENISZD1 can be a starburst galaxy at redshift of 7.8 (about 0.674 Gyr since the Big Bang), and is by far the most massive galaxy ever found at redshift greater than 7, which is difficult to be predicted by modern theoretical simulations. The existence of TENIS-ZD1, therefore poses a challenge to current theoretical models for how so much mass can accumulate in a galaxy at such an early time in the Universe. Upper figure: false-color composite image of TENIS-ZD1. This image shows TENIS-ZD1 as seen by the Hubble Space Telescope in 0.85μm (blue), the CFHT in 1.2μm (green), and the Spitzer Space Telescope in 3.6μm (red). The orangish TENIS-ZD1 indicates that it is a z’ -dropout source and is not detectable in optical wavelength. The two white nearby extended objects are low-redshift galaxies. Bottom figure: luminosity function at redshift~7. The red data point indicates our sample. Although the Capak11 sample is brighter than ours, the follow-up photometric observations for their sample suggest that they are more likely low-redshift objects. Our sample, TENIS-ZD1, is therefore by far the most luminous and massive galaxy ever found at redshift greater than 7.
Layer-by-layer Graphene/TCNQ Stacked Films as Conducting Anodes for Organic Solar Cells ACS Nano 6 (2012): 5031–5039.
Chang-Lung Hsu, Cheng-Te Lin, Jen-Hsien Huang, Chih-Wei Chu, Kung-Hwa Wei, and Lain-Jong Li Research Center for Applied Sciences, Academia Sinica
Large-area graphene grown by chemical vapor deposition (CVD) is a promising candidate for transparent conducting electrode applications in flexible optoelectronic devices. However, the power conversion efficiency of the polymer photovoltaic devices using a pristine CVD graphene anode is still not appealing due to its much lower conductivity than that of conventional indium tin oxide. We report a layer-by-layer molecular doping process on graphene for forming sandwiched graphene/tetracyanoquinodimethane (TCNQ)/graphene stacked films for polymer solar cell anodes, where the TCNQ molecules as p-dopants were securely embedded between two graphene layers. Poly(3-hexylthiophene)/phenyl-C61butyric acid methyl ester (P3HT/PCBM) bulk heterojunction polymer solar cells based on these multilayered graphene/ TCNQ anodes are fabricated and characterized. The P3HT/PCBM device with an anode structure composed of two TCNQ layers sandwiched by three CVD graphene layers shows optimum PCE (~2.58%), which makes the proposed anode film quite attractive for next-generation flexible devices demanding high Schematic of organic solar cell and graphene/TCNQ stacked film conductivity and transparency.
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Abstracts of Other Significant Publications
High-efficiency Broadband Anomalous Reflection by Gradient Meta-surfaces Nano Letters 12 (2012): 6223-6229.
Shulin Sun, Kuang-Yu Yang, Chih-Ming Wang, Ta-Ko Juan, Wei Ting Chen,Chun Yen Liao, Qiong He, Shiyi Xiao, Wen-Ting Kung, Guang-Yu Guo, Lei Zhou, and Din-Ping Tsai Research Center for Applied Sciences, Academia Sinica
Gradient-index meta-surfaces were found to exhibit extraordinary light-manipulation abilities within subwavelength lateral dimension, and gain lots of attentions recently. In this work, we designed and fabricated a gradient meta-surfaces working in near-infrared region (~850nm) with broad-band functionality (750nm–900nm) following the Generalized Snell’s Law, and demonstrated by both experiments and numerical simulations that it can redirect an input light to a nonspecular channel with high efficiency. Compared to previously fabricated meta-surfaces, our samples operate in a shorter wavelength and can reflect the incident waves to a single anomalous reflection with very high conversion efficiency (~80%), also, keep light polarization unchanged after the anomalous reflection. Our results can lead to many practical applications, such as polarization and spectral beam splitters, anti-reflection coating, light absorber, etc.
Enhancing Surface Plasmon Detection Using Template-stripped Gold Nanoslit Arrays on Plastic Films ACS Nano 6 (2012): 2931-2939.
Kuang-Li Lee, Pei-Wen Chen, Shu-Han Wu, Jhih-Bin Huang, Sen-Yeu Yang, and Pei-Kuen Wei Research Center for Applied Sciences, Academia Sinica
Nanostructure-based sensors are capable of sensitive and label-free detection for biomedical applications. However, high-throughput and low-cost fabrication techniques are the main issues which should be addressed. In this study, chip-based nanostructures for intensity sensitive detection were fabricated and tested using a thermalannealing-assisted templates tripping method. We found that a transverse magnetic-polarized wave in these gold nanostructures generated sharp and asymmetric Fano resonances in transmission spectra. The narrowest bandwidth was smaller than 10 nm. Compared to nanoslit arrays on glass substrates using electron-beam lithography, the proposed chip has a higher figure of merit and intensity sensitivity, up to 10367%/ RIU (refractive index unit). The higher intensity sensitivity for the templatestripped nanostructure is attributed to a smoother gold surface and larger grain sizes on the plastic film, which reduces the surface plasmon propagation loss.
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Propagation and Maintenance Mechanism of the TC/submonthly Wave Pattern and TC feedback in the Western North Pacific Journal of Climate 25 (2012): 8591-8610.
Ken-Chung Ko, Huang Hsiung Hsu, and Chia Chou Research Center for Environmental Changes, Academia Sinica
Propagation and maintenance mechanisms of the tropical cyclone/submonthly wave pattern in the Western North Pacific are explored. The mean flow advection played a dominant role in the propagation in both phases. Barotropic energy conversion is the dominant process in maintaining the kinetic energy of the pattern. When TCs developed in the submonthly wave pattern, they in turn enhanced the amplitudes of kinetic energy of the submonthly wave pattern by more than 50% and helped extract significantly more energy from the background intraseasonal oscillation (ISO) circulation. This TC feedback was much more significant in the ISO westerly phase because of the stronger clustering effect on TCs by the enhanced monsoon trough. This study helps understand the multiscale interaction in the Western North Pacific.
How Much do Precipitation Extremes Change in a Warming Climate? Geophysical Research Letters 39 (2012): L17707, doi:10.1029/ 2012GL052762.
Chein-Jung Shiu, Shaw Chen Liu, Congbin Fu, Aiguo Dai, and Ying Sun Research Center for Environmental Changes, Academia Sinica
Daily data from reanalyses of the European Centre for Medium-Range Weather Forecasts (ECMWF) and the National Centers for Environmental Prediction (NCEP) are analyzed to study changes in precipitation intensity with respect to global mean temperature. The results are in good agreement with those derived from the Global Precipitation Climatology Project (GPCP) data by Liu et al. (2009), providing an independent verification for large changes in the precipitation extremes: about 100% increase for the annual top 10% heavy precipitation and about 20% decrease for the light and moderate precipitation for one degree warming in the global temperature. These changes can substantially increase the risk of floods as well as droughts, thus severely affecting the global ecosystems. Atmospheric models used in the reanalysis mode, with the benefit of observed wind and moisture fields, appear to be capable of realistically simulating the change of precipitation intensity with global temperature.
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Abstracts of Other Significant Publications
Alternative Splicing of Arabidopsis thaliana P5CS1 Caused by Intron Sequence Variation is Associated with Environmental Adaptation Proceedings of the National Academy of Sciences of the USA 109 (2012): 9197-9202.
Ravi Kesari, Jesse R. Lasky, Joji Grace Villamor, David L. Des Marais, Ying-Jiun C. Chen, Tzu-Wen Liu, Wendar Lin, Thomas E. Juenger, and Paul E. Verslues Institute of Plant and Microbial Biology, Academia Sinica
Plant growth is deter mined by environmental factors with drought being one of the most critical restraints on agricultural productivity and distribution of natural plant populations worldwide. Environmental restraints on plant productivity are of increasing importance because of climate change and limited fresh water supplies for irrigation. Many plant species accumulate large quantities of free proline during drought stress; however, the adaptive value of proline has remained unclear. The model plant Arabidopsis thaliana is distributed across a wide geographic range and has become the leading model for studying environmental adaptation in plants. The laboratory of Paul Verslues, in collaboration with the group of Tom Juenger at the University of Texas, found that Arabidopsis accessions varied ten-fold in proline accumulation. Much of this variation was accounted for by high levels of a non-functional P5CS1 (△ 1-pyrroline-5-carboxylate synthetase ) splice variant in some accessions. Accessions having these high levels of the non-functional P5CS1 splice variant shared a specific set of intron polymorphisms. Correlation of P5CS1 splicing variation with climate data indicated a specific role of P5CS1 and proline synthesis in adaptation to differing climates. This study (Kesari et al., 2012 PNAS), identified a novel source of alternative splicing in plants, demonstrated a role of exon 3-skip P5CS1 in natural variation of proline metabolism, and suggested an association of P5CS1 and its alternative splicing with environmental adaptation.
Regulatory Mechanisms of an Acid-activated Type VI Secretion System in Agrobacterium tumefaciens PLoS Pathogens 8 (2012): e1002938.
Chih-Feng Wu, Jer-Sheng Lin, Gwo-Chyuan Shaw, and Erh-Min Lai Institute of Plant and Microbial Biology, Academia Sinica
The bacterial type VI secretion system (T6SS) is a widespread, versatile protein secretion system in many pathogenic Proteobacteria and has diverse functions that contribute to the survival or fitness of many pathogenic bacteria in response to environmental cues. Numerous studies have shown that T6SS is highly regulated via multiple mechanisms, but the regulatory mechanisms of most T6SSs remain unknown. In this study, Ph.D. student Chih-Feng Wu and postdoc Jer-Sheng Lin in Dr. Erh-Min Lai’s laboratory discovered that T6SS is activated by acidity via an ExoR-ChvG/ChvI cascade in a plant pathogenic bacterium, Agrobacterium tumefaciens (Wu et al., PLoS Pathogens, 2012). Further mechanistic studies indicated that ExoR represses ChvG sensor kinase by physical interaction and the acid-induced degradation of periplasmic ExoR may thereby derepress ChvG to activate T6SS by phosphorylation of the ChvI response regulator. This is the first report to unravel the molecular mechanisms underlying the acid-activated T6SS. The activation of T6SS by an acidic signal present in the wound site and intercellular space of plants implicates a role of T6SS during Agrobacterium –plant interactions.
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bZIP16 Integrates Light and Hormone Pathways to Regulate Early Seedling Development The Plant Cell 24 (2012): 3997-4011.
Wen-Ping Hsieh, Hsu-Liang Heish, and Shu-Hsing Wu Institute of Plant and Microbial Biology, Academia Sinica
Transcriptomic adjustment plays an important role in Arabidopsis seed germination and de-etiolation in response to environmental light signals. The G-box cis-element is commonly present in promoters of genes that respond positively or negatively to the light signal. We are interested in pursuing additional transcriptional regulators that modulate light-mediated transcriptome changes through binding to G-box and has identified bZIP16, a basic region/leucine zipper motif transcription factor, being a key regulator integrating light and hormone pathways. bZIP16 is a negative regulator in light-mediated inhibition of cell elongation but a positive regulator in light-regulated seed germination. Transcriptomic analysis supported that bZIP16 is primarily a transcriptional repressor regulating light-, gibberellic acid (GA)- and abscisic acid (ABA)-responsive genes. Chromatin immunoprecipitation study revealed that bZIP16 could directly target ABA-responsive genes and RGA-LIKE2 (RGL2) , a DELLA gene in the GA signaling pathway. bZIP16 could also indirectly repress the expression of PHYTOCHROME INTERACTING FACTOR 3-LIKE5 (PIL5) , which encodes a basic helix-loop-helix protein coordinating hormone responses during seed germination. By repressing the expression of these genes, bZIP16 functions to promote seed germination and hypocotyl elongation during the early stages of Arabidopsis seedling development.
Opposing Nodal and BMP Signals Regulate Left-right Asymmetry in the Sea Urchin Larva PLoS Biology 10 (2012): e1001402.
Yi-Jyun Luo, and Yi-Hsien Su Institute of Cellular and Organismic Biology, Academia Sinica
In bilaterally symmetric animals, the external appearance of their left side represents a mirror image of the right side. However, their internal organs are often left-right asymmetric. During sea urchin development, their body plans change from a bilateral gastrula to a penta-symmetric body plan. This transition relies on a left-right asymmetric control that results in the formation of the adult rudiment on the left side. We have shown that BMP signaling is required for the development of this left-sided structure, and the right-sided Nodal signaling induces cell death. These two signals establish left-right asymmetry in the sea urchin.
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Abstracts of Other Significant Publications
A Zebrafish Model of Intrahepatic Cholangiocarcinoma by Dual Expression of Hepatitis B Virus X and Hepatitis C Virus Core Protein in Liver Hepatology 56 (2012): 2268-2276.
Wangta Liu, Jim-Ray Chen, Chih-Hao Hsu, Yen-Hsing Li, Yi-Meng Chen, Chien-Yuan Lin, Shin-Jie Huang, Zen-Kuei Chang, Yen-Chun Chen, Chi-Hsueh Lin, Hong-Yi Gong, Ching-Chun Lin, Koichi Kawakami, and Jen-Leih Wu Institute of Cellular and Organismic Biology, Academia Sinica
TGF-β1 plays an important role in HBx- and HCP-induced ICC development. This in vivo model is a potential approach to study the molecular events of fibrosis and ICC occurring in HBV and HCV infection.
In Vivo Tagging and Characterization of S-Glutathionylated Proteins by a Chemoenzymatic Method
Angewandte Chemie International Edition 51 (2012): 5871-5875.
Identification of glutathione (GSH) S-thiolated proteins is achieved by introducing glutathionylsper midine sy nt het as e int o h u ma n c e l l s to l a b e l endogenous GSH with biotinyl spermidine. The proteins carrying desirable thiolation c an b e d et ect ed by i m mu n o bl o tti n g. Enrichment by using the biotin tag enabled subsequent MS-based proteomic analysis for site-specific identification of glutathionylated sites.
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B. Y. Chiang, C. C. Chou, F. T. Hsieh, S. Gao, J. C. Y. Lin, S. H. Lin, T. C. Chen, K. H. Khoo, and C. H. Lin Institute of Biological Chemistry, Academia Sinica
miR-103/107 Promote Metastasis of Colorectal Cancer by Targeting the Metastasis Suppressors DAPK and KLF4 Cancer Research 72 (2012): 1-11.
Hsin-Yi Chen, Yu-Min Lin, Hsiang-Ching Chung, Yaw-Dong Lang, Ching-Jung Lin, John Huang, Wei-Chi Wang, Feng-Mao Lin, Zhen Chen, Hsien-Da Huang, John Y. J. Shyy, Jin-Tung Liang, and Ruey-Hwa Chen Institute of Biological Chemistry, Academia Sinica
Metastasis is the major cause of poor prognosis in colorectal cancer (CRC), and increasing evidence supports the contribution of miRNAs to cancer progression. In this study, we found that high expression of miR-103 and miR-107 (miR-103/107) was associated with metastasis potential of CRC cell lines and poor prognosis in patients with CRC. miR-103/107 targeted the known metastasis suppressors deathassociated protein kinase (DAPK) and Krüppel-like factor 4 (KLF4) in CRC cells, resulting in increased cell motility and cell–matrix adhesion and decreased cell–cell adhesion and epithelial marker expression. miR-103/107 expression was increased in the presence of hypoxia, thereby potentiating DAPK and KLF4 downregulation and hypoxia induced motility and invasiveness. In mouse models of CRC, miR103/107 overexpression potentiated local invasion and liver metastasis effects, which were suppressed by reexpression of DAPK or KLF4. miR-103/107– mediated downregulation of DAPK and KLF4 also enabled the colonization of CRC cells at a metastatic site. Clinically, the signature of a miR-103/107 high, DAPK low, and KLF4 low expression profile correlated with the extent of lymph node and distant metastasis in patients with CRC and served as a prognostic marker for metastasis recurrence and poor survival. Our findings therefore indicate that miR-103/107– mediated repression of DAPK and KLF4 promotes metastasis in CRC, and this regulatory circuit may contribute in part to hypoxia-stimulated tumor metastasis. Strategies that disrupt this regulation might be developed to block CRC metastasis.
High-resolution Structures of Neotermes koshunensis β-Glucosidase Mutants Provide Insights into the Catalytic Mechanism and the Synthesis of Glucoconjugates Acta Crystallographica Section D-Biological Crystallography 68 (2012): 829-838.
W. Y. Jeng, N. C. Wang, C. T. Lin, W. J. Chang, C. I. Liu, and A. H. J. Wang Institute of Biological Chemistry, Academia Sinica
We report several high-resolution structures of wild-type or mutated Nk Bgl in complex with different ligand molecules. In the crystal structures of Nk Bgl E193A, E193S and E193D mutants Glu193 not only acts as the catalytic acid/ base but also plays an important role in controlling substrate entry and product release. Furthermore, in crystal structures of the Nk Bgl E193D mutant it was found that new glucoconjugates were generated by the conjugation of glucose (hydrolyzed product) and HEPES/EPPS/opipramol (buffer components). Based on the wild-type and E193D-mutant structures of Nk Bgl, the glucosidic bond of cellobiose or salicin was hydrolyzed and a new bond was subsequently formed between glucose and HEPES/EPPS/opipramol to generate new glucopyranosidic products through the transglycosylation reaction in the Nk Bgl E193D mutant. This finding highlights an innovative way to further improve β-glucosidases for the enzymatic synthesis of oligo-saccharides.
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Abstracts of Other Significant Publications
Two New Susceptibility Loci for Kawasaki Disease Identified through Genome-wide Association Analysis Nature Genetics 44 (2012): 522-525.
Yi-Ching Lee, Ho-Chang Kuo, Jeng-Sheng Chang, Luan-Yin Chang, Li-Min Huang, Ming-Ren Chen, Chi-Di Liang, Hsin Chi, Fu-Yuan Huang, Meng-Luen Lee, Yhu-Chering Huang, Betau Hwang, Nan-Chang Chiu, Kao-Pin Hwang, Pi-Chang Lee, Li-Ching Chang, Yi-Min Liu, Ying-Ju Chen, Chien-Hsiun Chen, Taiwan Pediatric ID Alliance, Yuan-Tsong Chen, Fuu-Jen Tsai, and Jer-Yuarn Wu Institute of Biomedical Sciences, Academia Sinica
Research team led by Academician Chen and Dr. Wu from Institute of Biomedical Sciences (IBMS), Academia Sinica collaborated with 15 physicians from 8 hospitals around Taiwan have identified two new chromosomal regions comprise BLK and CD40 respectively that could predispose individuals to Kawasaki disease through a genomewide association study. This important achievement leads to a better understanding of immune and inflammation activation in Kawasaki disease.
An Antinociceptive Role for Substance P in Acid-induced Chronic Muscle Pain Proceedings of the National Academy of Sciences of the USA 109 (2012): E97-E83.
Chia-Ching John Lin, Wei-Nan Chen, Chien-Ju Chen, Yi-Wen Lin, Andreas Zimmer, and Chih-Cheng Chen Institute of Biomedical Sciences, Academia Sinica
Chronic pain is a major medical problem. However, current analgesics are not effective in many types of chronic pain. Here we discovered a novel antinociceptive mechanism against acid-induced chronic muscle pain. This finding is essentially opposite to the role that substance P (SP) has been proposed to play over many years— SP signaling promotes pain. SP is an undecapeptide belonging to the tachykinin small peptide family. SP is an excitatory neurotransmitter that helps to excite and transmit pain signals. SP signaling is excitatory in almost all neuronal cells, Substances that inhibit SP signaling pathways generally show antinociceptive effects in animal models. However, though high levels of SP in muscle tissues and spinal fluid are frequently associated with chronic muscle pain, such as myofascial pain syndrome and fibromyalgia, researchers do not fully understand the role of SP in muscle pain. We have used mouse models to test how SP contributes to muscle pain sensitivity. In contrast to SP’s usually excitatory role, mice lacking SP signaling showed increased pain sensitivity after intramuscular acid injections, compared with mice with normal SP signaling. Both mice with null mutation of SP gene and those administrated with SP receptor antagonists showed similar increased sensitivity to muscle pain. We further used electrophysiological approach to identify an inhibitory signal pathway of SP that was found exclusively in muscle nociceptors expressing acid-sensing ion channel 3, where SP enhances M-type potassium channels through the NK1 receptor in a G protein-independent but tyrosine kinase-dependent manner. Thus, the intramuscular SP mediates an unconventional NK1 receptor signaling to inhibit acid-induced chronic muscle pain. The finding suggests that SP may inhibit pain sensitization in muscle nociceptors and increased SP in patients with chronic muscle pain may be present as part of an inhibitory feedback loop. This study opens up a new direction for pain research and also partially annotates the failure of clinical trials for analgesic drugs based on SP antagonism. The research team is now working on analgesic drug development against chronic muscle pain, such as fibromyalgia.
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Schematic model of substance P (SP)mediated inhibition of ASIC3 signaling. When tissue acidosis occurs in muscles, protons depolarize the muscle nociceptors by activating ASIC3 channels, and cause the firing of action potentials, which can release SP in the nerve terminals. SP then acts on NK1 receptors in the local nerve terminals. The NK1 receptors on muscle nociceptors are coupled with a G-proteinindependent signal pathway by activating tyrosine kinase and M channels to inhibit the ASIC3-mediated neural firing.
RNA Polymerase III Subunit Architecture and Implications for Open Promoter Complex Formation Proceedings of the National Academy of Sciences of the USA 109 (2012): 19232-19237.
Chih-Chien Wu, Franz Herzog, Stefan Jennebach, Yu-Chun Lin, Chih-Yu Pai, Ruedi Aebersold, Patrick Cramer, and Hung-Ta Chen Institute of Molecular Biology, Academia Sinica
Eukaryotic RNA polymerase III (Pol III) synthesizes tRNAs, 5S rRNA and certain small RNAs. Compared to eukar yotic RNA polymerase I (Pol I) and RNA polymerase II (Pol II), Pol III is the largest multi-subunit RNA polymerase with complex structural organization. Transcription initiation by Pol III relies on its C82/34/31 subcomplex, distantly related to the A49/34.5 subcomplex in Pol I and transcription factor TFIIE in the Pol II system. Here we combine crosslinking and hydroxyl radical probing to localize the C82/34/31 subcomplex around the Pol III active center cleft. The positioning of C82/34/31 in Pol III suggests the function of C82/34 in loading DNA into the active cleft during initiation and in maintaining the transcription bubble in the open promoter complex. Moreover, the results indicate that all C82/34/31-related components of eukaryotic and archaeal transcription systems adopt an evolutionarily conserved location in the upper part of the cleft that supports their functions in open promoter complex formation and stabilization.
(A) Western blot of C160-C82/C34 cross-links near the Pol III active center cleft.
(B) Model for Pol III open promoter complex.
Differential Age-dependent Import Regulation by Signal Peptides PLoS Biology 10 (2012): e1001416.
Yi-Shan Teng, Po-Ting Chan, and Hsou-Min Li Institute of Molecular Biology, Academia Sinica
Gene-specific, age-dependent regulations are common at the transcriptional and translational levels, while protein transport into organelles is generally thought to be constitutive. Here we report a new level of differential age-dependent regulation and show that chloroplast proteins are divided into three age selective groups: group I proteins have a higher import efficiency into younger chloroplasts, import of group II proteins is nearly independent of chloroplast age, and group III proteins are preferentially imported into older chloroplasts. The age-selective signal is located within the transit peptide of each protein. Two consecutive positive charges define the necessary motif in group III signals for older chloroplast preference. We further show that different members of a gene family often belong to different age-selective groups due to sequence differences in their transit peptides. These results indicate that organelle-targeting signal peptides are part of cells’ differential age-dependent regulation network. The sequence diversity of some organelle-targeting peptides is not a result of lacking selection pressure but has evolved to mediate regulation.
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Abstracts of Other Significant Publications
PHO2-Dependent Degradation of PHO1 Modulates Phosphate Homeostasis in Arabidopsis The Plant Cell 24 (2012): 2168-2183.
Tzu-Yin Liu, Teng-Kuei Huang, Ching-Ying Tseng, Ya-Shiuan Lai, Shu-I Lin, Wei-Yi Lin, June-Wei Chen, and Tzyy-Jen Chiou Agricultural Biotechnology Research Center, Academia Sinica
The Arabidopsis pho2 mutant, which is defective in a ubiquitin-conjugating E2 enzyme, displays Pi toxicity as a result of enhanced uptake and root-to-shoot translocation of Pi. To elucidate downstream components of the PHO2dependent regulatory pathway, we identified two pho2 suppressors as carrying missense mutations in PHO1 , which has been implicated in Pi loading to the xylem. We found that the protein level of PHO1 is increased in pho2 , whereas such accumulation is ameliorated in both pho2 suppressors. PHO1 and PHO2 are partially co-localized and physically interact in the endomembranes, where the ubiquitin conjugase activity of PHO2 is required for PHO1 degradation. We further showed that PHO1 degradation is PHO2-dependent and involves multivesicular body (MVB)-mediated vacuolar proteolysis. In addition, we presented a functional association between xylem loading and acquisition of Pi. Together, our PHO2-dependent degradation of PHO1 findings uncover a pivotal molecular mechanism by which PHO2 modulates the degradation of PHO1 in the endomembranes to maintain Pi homeostasis in plants. Co-localization and interaction of PHO1 and PHO2
Biological Degradation of Anthroquinone and Azo Dyes by a Novel Laccase from Lentinus sp. Environmental Science and Technology 46 (2012): 5109-5117.
Chih-An Hsu, Tuan-Nan Wen, Yu-Chang Su, Zhi-Bing Jiang, Chin-Wen Chen, and Lie-Fen Shyur Agricultural Biotechnology Research Center, Academia Sinica
Laccases are green enzymes which have been widely used in environmental bioremediation, biofuel production, biopulping and textile industries, and as bio-catalyst for compound synthesis or structural modification. However, highly efficient laccases with desirable properties to fulfill different industrial usages are still needed. This study identified a new Formosan white-rot fungal strain, Lentinus sp. that can produce extracellular form of laccases with a maximal activity reaching 58,300 U/ l in culture medium. A purified laccase (designated lcc3) was identified by LC-ESI MS/MS as an N -linkage glycosylated protein. Kinetic analyses revealed that the catalytic efficiency of lcc3 is novel compared to the currently published laccases. Lcc3 is highly thermostable with a midpoint temperature (T m) of 77.1oC; at 25 oC, the t 1/2 reached 118 h, and also stable in high organic solvent (methanol and ethanol) environment. Notably, we observed that Lentinus lcc3 can efficiently reduce the toxicity of anthraquinone (AB80) and azo (AR37) dyes on rice seed germination, decolorize industrial textile effluent, and remove certain degree of residue lignin in kraft pulp. Together, we identify a novel laccase enzyme from a new Taiwanese fungal strain which may be valuable for bioremediation and textile industry.
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Copper Homeostasis and Phytoremediation Plant Physiology 159 (2012): 1099-1110.
Lung-Jiun Shin, Jing-Chi Lo, and Kuo-Chen Yeh Agricultural Biotechnology Research Center, Academia Sinica
Many heavy metals are essential as trace nutrients for living organisms. These essential heavy metals can also cause toxicity at high levels. Plants have evolved a range of homeostasis mechanisms to minimize the harmful effects and maintain the concentration of essential metals within physiological limits. In Arabidopsis thaliana , two copper chaperones, antioxidant protein1 (ATX1) and ATX1-like Cu chaperone (CCH), share high sequence homology. The molecular mechanism involved in copper homeostasis was proposed. However, the biological importance of CCH and ATX1 in plants remains unknown. In this study, genetic and physiological approaches were employed. We demonstrate that ATX1 plays an essential role in copper homeostasis in conferring tolerance to excess copper and copper deficiency. The high Cu accumulation and tolerance of ATX1 overexpression lines with high concentration of Cu in the soil suggest the possible use of ATX1 for phytoremediation of Cucontaminants.
excess Cu
Effective Suppression of HCV Replication by Attenuating 40S Ribosomal Subunit Abundance PLoS Pathogens 8 (2012): e1002766.
Jing-Ying Huang, Wen-Chi Su, King-Song Jeng, Tien-Hsien Chang, and Michael M. C. Lai Genomics Research Center, Academia Sinica
Hepatitis C virus (HCV) is a blood-transmitted virus that causes chronic liver diseases threatening roughly two percent of the world’s population, yet current therapies are only effective in a fraction of infected patients. Conventional drug designs often target viral proteins, which invariably result in drug resistance due to rapid viral mutations. We used RNAi technology to search for host-cell components that HCV must employ to reproduce itself. This led us to the 40S ribosomal subunit components and show that, by reducing the level of the 40S ribosomal subunit in half, HCV replication can be significantly repressed without negatively impacting on the cell health. This finding thus opens up a new avenue for developing anti-HCV therapeutics. Because ribosomal 40S subunit has been perfected over millions of years of evolution, it is extremely unlikely to morph or mutate as freely as viruses. Thus, finding a good way to fine-tune the 40S ribosomal subunit level as part of the HCV therapeutics may not only be feasible, but also superior in terms of minimizing drug-resistance problem and maintaining the drug shelf life.
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Abstracts of Other Significant Publications
ASK1 Promotes Apoptosis of Normal and Malignant Plasma Cells Blood 120 (2012): 1039-1047.
Fan-Ru Lin, Shang-Yi Huang, Kuo-Hsuan Hung, Shin-Tang Su, Cheng-Han Chung, Atsushi Matsuzawa, Michael Hsiao, Hidenori Ichijo, and Kuo-I Lin Genomics Research Center, Academia Sinica
Terminally differentiated, antibodysecreting plasma cells are the endstage effectors of humoral immune responses. Although the overproduction of immunoglobulins by short-lived plasma cells accompanying an immune response links with their apoptosis, how long-lived plasma cells adapt to ensure their longevity in this context is obscure. Dr. Lin’s laboratory showes that apoptosis signal–regulating kinase 1 (ASK1) contributes to apoptosis of plasma cells. Antigen-specific long-lived plasma cells generated by immunization accumulated in ASK1deficient mice. Enforced expression of ASK1 in malignant plasma cells, multiple myeloma (MM), caused apoptosis in vitro and lowered MM load in a xenograft animal model. Additionally, a critical survival-related transcriptional repressor, Blimp-1, is crucial for silencing ASK1 in maintaining the survival of plasma cells. Our findings not only reveal a novel mechanism underlying the regulation of survival in normal and malignant plasma cells by ASK1 but also provide a new therapeutic insight into plasma cell diseases.
PGASO: A Synthetic Biology Tool for Engineering a Cellulolytic Yeast Biotechnology for Biofuels 5 (2012): 53.
Jui-Jen Chang, Cheng-Yu Ho, Feng-Ju Ho, Tsung-Yu Tsai, Huei-Mien Ke, Christine H-T Wang, Hsin-Liang Chen, Ming-Che Shih, Chieh-Chen Huang, and Wen-Hsiung Li Biodiversity Research Center, Academia Sinica
Synthetic biology is a field of translational research that combines science and engineering. It has been dubbed the source of a possible “biological” industrial revolution. It is the design and assembly of the bio-bricks into genetic circuits for new biological entities and systems. A research group led by Academician Wen-Hsiung Li developed a simple one-step method for simultaneously introducing multiple genes into a yeast host. The technique, named Promoter-based Gene Assembly and Simultaneous Overexpression (PGASO), employs overlapping oligonucleotides for recombinatorial assembly of gene cassettes with individual promoters. PGASO was applied to engineer Kluyveromyces marxianus KY3, which is a thermo-and toxin-tolerant yeast. A recombinant strain, KR5, that is capable of simultaneously expressing exoglucanase and endoglucanase (EGⅢ and CBHI both of Trichoderma), aβ-glucosidase (NpaBGS from a cow rumen fungus), a selection marker (KanMX), and a fluorescent protein (GFP), was obtained. High transformation efficiency and accuracy were achieved (~63%). It achieved the cellulosic ethanol for bio-fuel. The study showed the potential of PGASO for establishing a cell factory for bio-production.
PAGSO:Synthetic biology platform and its applications
Five gene cassettes for PGASO assembly
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Incompatibility and Competitive Exclusion of Genomic Segments between Sibling Drosophila Species PLoS Genetics 8 (2012): e1002795.
Shu Fang, Roman Yukilevich, Ying Chen, David A. Turissini, Kai Zeng, Ian A. Boussy, and Chung-I Wu Biodiversity Research Center, Academia Sinica
Determining the extent of genomic incompatibilities is a pivotal issue in understanding the process of speciation. Here, we present a new perspective by shifting the focus from the species divergence at the DNA sequence level to the fitness and functional aspects of foreign genomic introgression. To illustrate our point, we perform a 20-generation competition experiment between introgressed random genomic segments of Drosophila sechellia and their D. simulans counterparts in the genetic background of D. simulans . The result reveals that even at the early stages of speciation, there are virtually always detrimental fitness consequences to introducing random foreign elements from one genome to another. This implies that incipient speciation may All Drosophila sechellia introgressed alleles in the genetic background of D. simulans rapidly decrease in frequency. be characterized by widespread accumulation of genomic incompatibilities rather than a few isolated genes. This study shows that we should move beyond the sterility and inviability assays in order to understand the full extent of genetic incompatibilities during speciation.
Unfavourable Environment Limits Social Conflict in Yuhina brunneiceps Nature Communications 3 (2012): 885.
S. F. Shen, S. L. Vehrencamp, R. A. Johnstone, H. C. Chen, S. F. Chan, W. Y. Liao, K. Y. Lin, and H. W. Yuan Biodiversity Research Center, Academia Sinica
Ta i w a n y u h i n a s ( p i c t u re d ) a re a j o i n t nesting species of birds where group members within a nest are unrelated.Shen et al .Show that unfavourable environmental conditions reduce social conflict and make the bird more cooperative, a strategy that results in higher offspring survival.
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Abstracts of Other Significant Publications
A Doctor to Empire: Patrick Manson and the Founding of British Tropical Medicine Taipei: Asian Culture Publishing, 368 pages, 2012.
Shang-Jen Li Institute of History and Philology, Academia Sinica
The British physician Patrick Manson (1844-1922), known as the father of tropical medicine, is an important figure in the history of modern medicine. His research of elephantiasis uncovered the role of mosquitoes in the transmission of filariasis, in what amounted to the first demonstration of the role of insects as vehicles of transmission for certain parasitic diseases. Manson subsequently hypothesized that mosquitoes were hosts for the plasmodium (malaria parasite) as well, and together with Ronald Ross, a British medical officer in India, uncovered the parasite’s mode of transmission. Ross was awarded a Nobel Prize for this work. During his early years in China, Manson conducted his research on filaria while serving as a medical officer to the Chinese Imperial Maritime Customs in Amoy. He later took up private practice in Hong Kong where he founded the Hong Kong College of Medicine for Chinese together with the British physician James Cantlie. (Sun Yat-sen was a graduate of the first class of the school.) After returning to England, Manson served as Medical Advisor to the Colonial Office, and founded the London School of Tropical Medicine. Drawing on a wealth of primary sources including unpublished letters, diaries, and journals, A Doctor to Empire analyzes Mason’s scientific research and work as a physician in the context of contemporary medical knowledge and against the backdrop of the expansion of the British Empire. The book provides a detailed exposition of Manson’s career and the establishment of the specialty of tropical medicine.
Religion, Identity and Adjudication in the Song Dynasty Beijing: Zhonghua Book Co., 324 pages, 2012.
Nap-Yin Lau Institute of History and Philology, Academia Sinica
A great number of Buddhist monks during the Song committed crimes, partly due to the laxity of discipline within the Buddhist community, and partly to the ineffectiveness of restraints from secular society. Not a few scholarofficials and lay people induced monks to commit wrongdoings in what constituted so-called collective crimes. Judgments passed on these monks were mostly grounded in law and made little or no consideration of their religious identity. Concubines were not only female, but also similar to “the other woman” today, and thus seemed to belong to a disadvantaged group. However, their rights or interests were greatly enhanced during the latter half of the Southern Song. Concubines were allowed to obtain pension funds from spousal patrimony as well as establish heirs for husbands who had died heirless. Why were the scholar-officials of the Song so preferential to widowed concubines? This might have to do with the civil examinations, through which many commoners became legislators and judges, and the values of the ruled class were assimilated to those of the ruling class, leading to a variety of changes.
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Family Relationship Quality and Its Psychological Effects among Taiwanese Adolescents In Chin-Chun Yi (Ed.), The Psychological Well-being of East Asian Youth , Dordrecht: Springer Publishing Co. (2012): 69-88.
Yuh-Huey Jou Institute of Ethnology, Academia Sinica
This study examines the influence of the characteristics and interactive factors of family relationship quality and its effect on various psychological well-being indicators among Taiwanese adolescents. Since grandparents are the basic family unit in the Chinese system, the research framework incorporates both paternal and maternal grandparents in addition to both parents and siblings in the construction of family relationship quality. Data (n = 2310) were based on a panel study conducted by the Taiwan Youth Project in 2005 (12th grade) and 2007 (14th grade). Latent class models and multiple regression models were used to generate adolescents’family relationship quality, which can be categorized into Paternal Grandparents Close, Distant, Multiple Close, and Nuclear Close . The results confirm that adolescents’family cohesion, self-esteem, and 0.0416 Distant 0.1024 depression vary by their family Multiple Close relationship quality patterns. The particularity of East Asian adolescents is briefly 0.2047 Nuclear Close discussed. 0.6512 Paternal Grandparents Close
Institutional Transplantation: The Chinese Lawyers in Republican Shanghai (1912–1937) Taipei: Institute of Modern History, Academia Sinica, 412 pages, 2012.
Huei-Min Sun Institute of Modern History, Academia Sinica
This book examines the development of Western-style Chinese lawyers in early Republican Shanghai. It explores how various political and social forces wrestled and negotiated with one another to ensure the legal basis for the very existence of lawyers and to shape the regulations of legal practice. The introduction of Western-style lawyers also changed the existing concepts of occupations or professions. Increasing numbers of people measured the status of an occupation by how much specialized knowledge the practitioners had to learn. The scattered and self-employed working style of professional workers made them a unique occupational category, that is, members of the so-called ziyou zhiye (free professions). In order to strengthen its control of the “free”professional workers, the Chinese government forced Chinese lawyers to organize bar associations, but these authorized associations, especially the Shanghai Bar Association, fostered a sense of community among the scattered lawyers and became a channel to promote the professional rights of lawyers.
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Abstracts of Other Significant Publications
Domination and Disintegration : Communist Revolution in Hebei, 1921–1949 Taipei: Institute of Modern History, Academia Sinica, 510 pages, 2012.
Yao-Huang Chen Institute of Modern History, Academia Sinica
The Chinese Communist Party was born in a divided Chinese society. The party could not dominate this divided society by the power of organization from the top down, nor did it want to be engulfed by this society. Therefore, on the one hand the CCP had to tolerate the diversity of this society through the united front strategy, and on the other hand the party had to again tear Chinese society apart through class struggle, in order to dominate the united front and diversity of society. Then the CCP was able to build an enormous party-state on the foundations of this dichotomized society. The history of Communist revolution in Hebei is a concrete example of this process.
Money and the Welfare Cost of Inflation in an R&D Growth Model Journal of Money, Credit, and Banking 45 (2013): 233-249.
This study analyzes the effects of inflation on R&D and innovation-driven growth. In the theoretical section, we incorporate money demand into a qualityladder model with elastic labor supply and derive the following result. If the elasticity of substitution between consumption and the real money balance is less (greater) than unity, then R&D and the growth rate of output would be decreasing (increasing) in the growth rate of money supply. Quantitatively, decreasing inflation in the US to achieve price stability improves social welfare, and the welfare gain is equivalent to at least 0.5% of annual consumption. In the empirical section, we use crosscountry data to establish a negative and statistically significant relationship between inflation and R&D.
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Angus C. Chu and Ching-Chong Lai Institute of Economics, Academia Sinica
Optimal Factor Tax Incidence in Two-sector Human Capital-based Models Journal of Public Economics 97 (2013): 75-94.
Been-Lon Chen and Chia-Hui Lu Institute of Economics, Academia Sinica
This paper studies the optimal factor tax incidence in a standard two-sector, human capital-based endogenous growth model elucidated by Lucas (1988). Capital income taxes generate dynamic inefficiency for capital accumulation and labor income taxes create dynamic inefficiency for human capital accumulation. A factor tax incidence is a tradeoff between these two inefficiencies. A switch from capital income taxes to labor income taxes reduces the long-run welfare coming from lower leisure and increases the long-run welfare originated from higher economic growth and higher consumption. Because the representative agent's learning time and human capital are inseparable and thus affect learning activities at the same degree, we find that based on the current US income tax code, it is optimal to first tax capital income, and to resort to taxing labor income only when tax revenue is insufficient to cover government expenditure.
The Other Taipei: Asian Culture, 184 pages, 2012.
Yu-Cheng Lee Institute of European and American Studies, Academia Sinica
This book begins with a discourse on the historical importance of the Other, which is followed by analyses of various biblical, literary and visual texts about fear, denial and suppression of the Other. The rest of the book discusses a number of issues closely related to the Other, including globalization, postmodern war, transculturalism, etc. The cultural texts under discussion indicate that although issues surrounding the Other are ancient, they are not yet outmoded. From biblical times to the events of today, the Other and related issues have never faded from our cultural imagination. It is the conviction of the author that in a world fraught with prejudice, ignorance, and hatred, the manner in which we confront, understand, recognize, and accept the Other is not only an academic problem but also an ethical one.
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Abstracts of Other Significant Publications
Representative Contact Diaries for Modeling the Spread of Infectious Diseases in Taiwan PLoS One 7 (2012): e45113.
doi:10.1371/journal pone.0045113.
Yang-Chih Fu, Da-Wei Wang, and Jen-Hsiang Chuang Institute of Sociology, Academia Sinica
In this study we apply contact diaries and social surveys to epidemiological inquiries about how infectious diseases spread across socio-demographic groups. Using 3-stage systematic probability sampling and in-person household interviews in a national survey, we collected 1,943 representative 24-hour contact diaries. Nearly 70% of the 24,265 face-to-face contacts recorded in these diaries occurred outside of respondents’ households. The most active age group was 5–14, who averaged around 16–18 daily contacts, about 2–3 times as many as the least active age groups. From these contact patterns we derive key parameters of social mixing to modify a sophisticated national simulation system. While the realistic data help us better model and estimate how soon pandemic diseases may develop, the sampling design enables us to infer the findings to the whole population in Taiwan. Our research results should help implement more appropriate and effective strategies for controlling an emerging disease infection.
New Horizons in the Study of the Chinese Classics Taipei : Wan Juan Lou Books Company Limited, 222 pages, 2012.
Ching-Chang Lin Institnte of Chinese Literature and Philosophy, Academia Sinica
New Horizons in the Study of the Chinese Classics brings together ten essays, grouped under three different topics. First, the formation and decline of authority based on classics; secondly, two recurring patterns in the interpretation of the classics: the alternation of simple and complex commentaries, and the movement of a return to the texts; thirdly, three major problems associated with the Book of Odes: the moral values reflected in the work, the place of the “Great Preface,” and the movement to challenge the “Great Preface.”
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The Scholarship and Thoughts of Le Quy Don Taipei: Institute of Chinese Literature and Philosophy, Academia Sinica, 359 pages, 2012.
Tsai-Chun Chung (editor) Institute of Chinese Literature and Philosophy, Academia Sinica
Le Quy Don is a famous scholar and statesman in the later Le dynasty. Being an encyclopedic scholar he composed more than fifty works. In addition to his versatile learning, Le communicated with Chinese and Korean scholars and learned some Western knowledges when acted as deputy envoy to Beijing in 1760-1762. In this way his scholarship can be studied not only as a comparison between Chinese and Vietnamese cultures, but as an epitome of communication of East Asian scholarships. Articles in this symposium are selected and edited from the four conferences on Vietnamese Confucianism from 2009 to 2012 organized jointly by this institute and the Institute of Philosophy, Vietnam Academy of Social Sciences. This is the first book on Le Quy Don in Chinese in the world. The book exhibits not only the good discipline of Taiwan scholars in classical Chinese but also their broad knowledge in both Chinese and East Asian Confucianism, which are necessary tool for studying Vietnamese Confucianism.
Redeeming the Pariah, Redeeming the Past: Some Taiwanese Reflections on the Murayama Statement Japan and Reconciliation in Post-war Asia: The Murayama Statement and Its Implications, New York: Palgrave Macmillan (2013): 68-90.
Rwei-Ren Wu Institute of Taiwan History, Academia Sinica
This chapter interprets the Murayama Statement from the perspective of the Taiwanese as a pariah in international politics. The geopolitical vulnerability of Taiwan brought about successive and multiple victimizations in its modern history and eventually locked it into diplomatic isolation. However, the vulnerable position of the pariah enables the Taiwanese to recognize that historical injustice is inherently repeatable-especially to the weak-and that building universally effective preventive mechanisms is no less important than reparations in specific cases. The author offers a Kantian reading of the Statement by praising and emphasizing its universalistic commitment to democratic peace and proposes that Japan pursue a progressive project of democracy promotion centered on civil society aid in East Asia, especially China, as a meaningful way to repay its historical debt and achieve true reconciliation.
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Abstracts of Other Significant Publications
Japanese Rule and Colonial Chinese Language—— Status and Vision of Chinese Language in Taiwan Tokyo: Sangensha Publishers Inc., 360 pages, 2012.
Pei-Feng Chen Institute of Taiwan History, Academia Sinica
Japan-ruled Taiwan was the melting pot of modern Chinese language. The “same language” (ideograms) cultural setting nurtured a new integrated language-colonial Chinese language. To know more about colonial Chinese language, this book discusses several important issues. First, the literature debate on Chinese and Taiwanese during 1920-30 Taiwan was in essence for making consistent the spoken and written language on the basis of colonial Chinese language. Moreover, the convenience of dual ‘same language,’ Chinese and Japanese, had transformed Taiwan from traditional to modern without literacy education. Such transition based on Taiwan’s adoption of ‘foreign’ literary forms for its rapid modernization which further refined its local language. Finally, multiple sources of language in colonial Taiwan served different purposes and readers, was constantly shaping the boundaries of the literary community. The language setting in colonial Taiwan was founded on the ‘written’ language. As a result, beyond the sovereign, colonial Chinese language was dominating the literary scene in Taiwan. In the same vein, following the collapse of the ‘same race’ political implications, colonial Chinese language was ruled out and put under ban.
Katana and Lancet: The Transformation, Assimilation and Diffusion of Western Medicine in Japan Taipei: National Taiwan University Press, 242 pages, 2012.
Shi-Yung Liu Institute of Taiwan History, Academia Sinica
The book mainly aims to portray the transformation, assimilation and diffusion of western medicine from Tokugawa samurai society to early Meiji state. Katana and Lancet does not mean to bring a final observation to the relationship between Tokugawa Confucianism and Japanese modern medicine, but aim to slightly compensate the influence of technology-oriented and pragmatic historiography. The book contains six chapters. The writing is based on timeframe which is marked with key events while the discussion unveils the rise of medical tycoon, a significant phenomenon in early Meiji Japan. The narrative lights up the roles of samurai physician in promoting western medicine while maintained the traditional norms. The author hopes to portray the diffusion of western medicine to Japan was a process of transformation and assimilation which western medicine has been converted with traditional Confucian norms and cultural imagination. The book is also a late overture of author's book in 2009.
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Nominal Tense in Tsou UCLA Working Papers in Linguistics, Theories of Everything 17 (2012): 43-58.
Henry Y. Chang Institute of Linguistics, Academia Sinica
This paper investigates an understudied topic -nominal tense (NT) in the Formosan language Tsou. In light of the NT diagnostics proposed in Nordlinger and Sadler (2004), this paper analyzes the nominal temporal marker nia as an instance of Independent NT (INT), heading a DP-internal tense phrase (TP). The INTanalysis explains nicely why (i) nia makes a temporal distinction of past versus nonpast within a noun phrase, (ii) nia cannot be replaced by a verbal tense/mood auxiliary, (iii) the meaning of nia is rather abstract— nia applies widely to nouns of various kinds, including nouns denoting artifacts, location and time, (iv) nia is normally preceded by a case marker, (v) a verb is required to undergo nominalization upon patterning with nia , (vi) nia is compatible both with definite and indefinite noun DP phrases, (vii) nia can co-occur either with a realis auxiliary or an irrealis auxiliary. These findings may advance our understanding of Tsou nominal structure on the one hand and shed new lights on the universal nominal structure on the other (cf. Cinque 2005, 2011).
A Study of Saisiyat Morphology Language and Linguistics Monograph Series,
Taipei: Institute of Linguistics, Academia Sinica: in press.
Elizabeth Zeitoun, Tai-Hwa Chu, and Lalo a Tahesh Kaybaybaw Institute of Linguistics, Academia Sinica
The present monograph provides an in-depth study of the morphology of Saisiyat (Tungho dialect), a Formosan language spoken in north-western Taiwan in Miaoli County. The present manuscript is over 600 pages and is divided in ten chapters. It begins with an overview of the Tungho Saisiyat grammar (including its phonology and morphosyntax) and goes on to examine the morphological units, morphological processes, and major lexical categories of this language as a basis for the study of its nominal and verbal morphology (including valency-changing operations (causativity, reflexivity and reciprocity). It also discusses nominalization (i.e. the process that derives a noun from a verb through root modification) and composite verbs (affixed verbal and nominal roots as well as numerals). The morphological analysis is cast in terms of the morpheme-based approach.
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Abstracts of Other Significant Publications
Assessing Political Biases in Vote-buying Verdicts in Taiwan The China Quarterly 211 (2012): 786-805.
Chung-Li Wu Institute of Political Science, Academia Sinica
Widespread vote buying is a major characteristic of Taiwan’s election politics and this malpractice has been an issue of great concern to many on the island. Some common sayings in the Taiwanese dialect describe the prevalence of vote buying: for one, “elections have no master and can be bought with money; ”and another,“ if you spend money you are not guaranteed to win the election, but if you do not spend money, you are guaranteed to lose it.”To make matters worse, the general public does not seem to trust the courts to be independent of political influences. This study employs the literature of vote buying and voter mobilization as the theoretical framework, and the data analyzed in this study were collected from the Law and Regulations Retrieving System, the Judicial Yuan of the Republic of China. This study examines the impact of political variables (including partisanship, whether candidates are elected or not, and the type of election) on court decisions at three levels-district courts, high courts, and the Supreme Court-for vote-buying litigation between January 2000 and December 2010. During this period, district courts reached judgment on 7,886 defendants, the high courts 4,696 defendants, and the Supreme Court 762 defendants. This study constructs hierarchical logistic regression models, and the empirical findings indicate that the effects of political factors are considerably less an influence than expected on trial outcomes. The results also demonstrate no strong support for some folk sayings about The Frequencies of Vote-buying Cases in Taiwan, 2000-2010 Unit: Defendant the judicial system revealing the negative stereotypes of votebuying verdicts; for example, “the courts are dominated by the Kuomintang (KMT)” (or the courts only charge the Green camp not the Blue one); “those elected will be let off, but those losing the elections will be imprisoned;” “those with good social connections won’t have any problem, but those without The Supreme Court High Courts connections will have big trouble;” “at the first trial a heavy District Courts sentence is passed, at the second trial the sentence is halved, and at the third trial the case is quashed. ”Taken as a whole, it appears that there is a gap between court verdicts in vote-buying cases and the way they are popularly perceived. Undoubtedly, judicial politics deserves further academic research.
Differing Mandates and Party Loyalty in Mixed-member Systems: Taiwan as a Baseline Case Electoral Studies 31 (2012): 384-392.
Nathan F. Batto Institute of Political Science, Academia Sinica
Mixed-Member electoral systems produce two types of legislators: list and district legislators. Theoretically, since district legislators must respond to both party and constituency demands while list legislators only need heed party demands, district legislators should be more likely than list legislators to vote against their party in roll call votes. This hypothesis has been tested in at least 21 different papers covering nine countries. However, the empirical evidence is very weak, with most cases showing no pattern and as many results in the opposite direction as in the expected direction. The various authors propose six distinct reasons that the hypothesis fails in their test. First, the party system may be suffocatingly strong or overly weak. Second, re-election may not be allowed. Third, there may be too many safe seats. Fourth, the power to determine nominations may be concentrated at the national level, and local forces may not have any influence over the nomination process. Fifth, legislators may be able to simultaneously register as both district and list candidates. Sixth, the party list may not be determined by a closed-list rule. Fortunately, none of these six conditions holds in Taiwan, making Taiwan an ideal critical test case. If the hypothesis fails in Taiwan, perhaps it is fatally flawed. In this paper, I analyze roll call data from the Taiwanese Legislative Yuan from 1993 to 2007 using a multi-level logit model. In fact, the hypothesis finds strong support in Taiwan: district legislators are much more likely to defect from the party line. Rather than a flawed theory, what we have seen is a complex world in which other variables mask the effect of the electoral system on party cohesion.
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Can Compulsory Health Insurance be Justified? An Examination of Taiwan's National Health Insurance Journal of Law and Health 26 (2013): 52-101.
Chuan-Feng Wu Institutum Iurisprudentiae, Academia Sinica
Compulsory insurance, or individual mandate, is the most important yet controversial linchpin in Taiwan National Health Insurance (NHI) system and has drawn close scrutiny regarding its constitutionality because a direct and unconditional requirement for an individual to transfer money to a universal health insurance program seems significantly violate individual liberties, especially the “disenrollment Step 1 Examine burdens on human rights freedom”. Even though Taiwan’s Constitutional Court held in Shizi No. 472 that the NHI’s individual mandate is not unconstitutional because the restriction on individual Clarify the purposes of health care policies liberty is justified as a means to promote social welfare • clear purposes and to improve national health, it failed to analyze the Step 2 • adequate relationship extent of the restriction in depth. Thus, a monitorable four-step systematic examination is proposed in this paper to explore the human rights burdens that the Evaluate effectiveness of health care policies NHI’s individual mandate places on individual liberty. Step 3 This paper concludes that, even though Taiwan’s Assess trade-off relationships in health care policies compulsory NHI, which adopts a single payer system • importance test – moral powers with a universal standardized medical coverage, is – lexical order of liberties adequate and effective, such a coercive healthcare Step 4 policy still unjustifiably restricts individuals’ freedom to purchase/decline health insurance because it is not the Priority rule Public interest rule least intrusive alternative and provides no proper trade-off between restricted liberty and pursued public order. Human Rights Impact Assessment for Health Care Policy
Demokratische Willensbildung vor Grundrechtlicher Rahmenordnung: Verfassungsrechtliche Überlegungen zur Auseinandersetzung von Gärditz und Zaczyk Der Staat 51 (2012): 233-250.
Shu-Perng Hwang Institutum Iurisprudentiae, Academia Sinica
This article gives insights into the constitutional aspects of the debate between Gärditz and Zaczyk on the legitimacy of criminal legislation. Through analyzing the main points of this debate, this article re-examines the relationship between constitutional rights and democratic legislation. It thereby stresses that, with their open, “framework-oriented” structure, the constitutional rights develop their binding force exactly through obliging the democratic legislators to realize individual freedom in pluralistic society. Viewed this way, the criminal legislation cannot be justified solely on its democratic basis. Rather, it is bounded by the framework order of the constitutional rights, according to which the criminal legislators are not allowed to sacrifice individual freedom just because it runs counter to the value judgments of the majority.
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Abstracts of Other Significant Publications
Party Capability versus Court Preference: Why do the“Haves”Come Out Ahead ?- An Empirical Lesson from the Taiwan Supreme Court Journal of Law Economics & Organization : in press.
Kong-Pin Chen, Kuo-Chang Huang, and Chang-Ching Lin Research Center for Humanities and Social Sciences, Academia Sinica
Using civil appeals data on Taiwan’s Supreme Court (TSC), this article revisits the well-known question of whether the “haves” come out ahead in litigations. Our study finds that the higherstatus litigants indeed tended to mobilize more sizeable and experienced legal representation than the lower-status litigants, a fact only implicitly assumed in the past literature. The “haves” were also more likely to prevail before the TSC than the “havenots.” More significantly, the advantage of the “haves” over the “have-nots” in TSC litigation holds even after the disparity of legal representation is controlled for. Further analysis reveals that the higher win rate enjoyed by the “haves” is mainly a consequence of the TSC’s decision of whether to hear the case on the merits. In contrast to the past literature which shows that the court tries to balance the disadvantage of the “have-nots” in its ruling, we show that in exercising its discretionary jurisdiction, the TSC strongly favored the “haves.” Once the TSC decided to adjudicate the appeal on the merits, neither the type of litigant nor the status of legal representation affected the final outcome. Our results thus show that both party capability and court preference contribute to influence the outcomes of appeals.
Effect of Age on the Incidence of Acute Hepatitis B after 25 Years of a Universal Newborn Hepatitis B Immunization Program in Taiwan The Journal of Infectious Diseases 205 (2012): 757-62.
W. J. Su, C. C. Liu, D. P. Liu, S. F. Chen, J. J. Huang, T. C. Chan, and M. H. Chang Research Center for Humanities and Social Sciences, Academia Sinica
This study focus on identifying the trend of acute hepatitis B (AHB) incidence after 25 years of a universal newborn hepatitis B immunization program in Taiwan and evaluating the need for a booster vaccine for cohorts who received the HBV vaccination in infancy. Since 1984, Taiwan began to immunize high risk newborns. However, the universal vaccination of hepatitis B started from 1986. The study results found the vaccination coverage rate of HBV reached 86.9-98.0% in the cohort after 1986. Nationwide AHB incidence declined from 1.76/100,000 in 2001 to 0.89/100,000 in 2008. The highest average incidence was at age 25-39 (2.33/100,000). The lowest average incidence was at age 1-14 (0.04/100,000). In overall, the vaccinated cohort had lower risk to get AHB infection than unvaccinated cohort during age 15-24 (rate ratio: 0.42, 95% CI: 0.28-0.62). In addition, AHB incidence at age under 14 was quite low in the last decade. Our results suggested that there was no urgent need to consider booster hepatitis B vaccinations for the vaccinated cohorts, but for the 25-39-year-old age group and the infants born from mothers w i t h H B V i n f e c t i o n w e re n e e d e d t o enhance vaccination program.
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Significant Research Achievements of Academia Sinica
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2012
Significant Research Achievements of
ACADEMIA SINICA
2012