3Rd NGS Student Symposium

3rd NGS Student Symposium

February 28, 2011

Venue supported by: Shaw Foundation Alumni House Organizing Commitee Lin Aigu Priscilla Ang Abdul Qader Al-Aidaroos Chung Kai Sheng, Bevan Daniel Dahlmeier Hao Hanfang Christine Koo Lim Jing Yan Lin Guan Hui Alvin Loo Sampath Jeewantha Wijesinghe Wu Yongzhi Daniel Yim Zhang Xuan

Description of cover logo As a computational linguist, I am interested in the application of artiﬁcial intelligence to human language. For my logo submission for this year’s NGS student symposium, I used a webservice called “wordle” (www.wordle.net) to automatically create a word cloud from the content of the NGS website. Notice how the algorithm automatically indentiﬁes the important words that decribe NGS, like Research, Sciences, Engineering, and of course the goal of every student: Graduate ;) Daniel Dahlmeier

Venue:

Auditorium (2nd Storey) Shaw Foundation Alumni House

1 Kent Ridge Drive Singapore 119244 Welcome

NGS Scholars’ Alliance warmly welcomes you to the 3rd NGS Student Sym- posium held in the Shaw Foundation Alumni House. NGS Scholars’ Alliance is the official student body for NGS students. It was established in December 2005 to serve as a platform for intellectual exchange and interaction among all NGS scholars. NGS Student Symposium is an annual conference organised by the NGS Scholars’ Alliance. The aims of the symposium are to foster effective communication between NGS students and their supervisors, give NGS students an opportunity to showcase their research findings and promote interaction between NGS students and renowned scientists of different fields. Since its inception in 2008, the NGS Student Symposium has grown from strength to strength. This year, we received a total number of 78 abstracts submitted for oral and poster presentations. This would not have been possible without the participation of all NGS students who have submitted abstracts for either oral or poster presentations and the organizing committee would like to thank all participants for their efforts. To enhance technical information exchange among researchers of similar fields, we have segmented the symposium into two sessions; First, the Phys- ical Sciences and Engineering and second, the Chemistry, Biology and Medical Sciences. This year, it is our great privilege to have with us, Professor Anthony Zee and Professor Ding Jeak Ling, as our honorary invited speakers. We would like to take this opportunity to extend our heartfelt gratitude to the NUS Office of Alumni Relations for kind sponsorship of this venue. In addition, we would like to thank Ms. Ivy Wee, Ms. Irene Chuan and Ms. Angela Poon for their constant support and invaluable advice. All in all, this symposium is dedicated to encourage networking and scientific exchange among research students and professors. It would have been impossible without your contribution, feedback and constructive suggestions. If you have any suggestion or a keen interest in helping NGS organize quality meetings such as this, please do not hesitate to contact us or Ms. Ivy Wee ([email protected]). With this, we thank all of you for your participation and have a fruitful conference!

NGS Scholars’ Alliance [email protected]

i Programme

08:00 – 09:00 Registration and poster setup Session 1: Physical Sciences and Engineering

09:00 – 09:05 Welcome and Session 1 Opening address Professor Barry Halliwell, D. Phil, D.Sc Deputy President (Research and Technology) National University of Singapore

09:05 – 09:50 The importance of interdisciplinary perspective in theoretical physics Professor Anthony Zee, Ph. D. Professor of Physics Department of Physics University of California, Santa Barbara

09:50 – 10:00 Q&A

10:00 – 10:30 Presentation 1 A Universal Relation between Heat Conduction and Diﬀusion Liu Sha

10:30 – 11:00 Tea break and poster session

11:30 – 12:00 Presentation 2 Automated Aesthetic Enhancement of Videos Xiang Yangyang

12:00 – 12:30 Presentation 3 Development of an Health Monitoring System for the Elderly Yuan Jian

12:30 – 13:30 Lunch and poster session

ii Session 2: Chemistry, Biology and Medicine

13:30 – 14:20 Many Roads in Research – Reinvent oneself? Professor Ding Jeak Ling, Ph. D. Department of Biological Sciences National University of Singapore

14:20 – 14:30 Q&A

14:30 – 15:00 Presentation 4 Building 3D Tissue Structures With Polyelectrolyte Fibers Toh Kah Chin Jerry

15:00 – 15:30 Tea break and poster session

15:30 – 16:00 Presentation 5 Linc-ing Neurogenesis – Long Non-coding RNAs Determine Neural Stem Cell Fate Ng Shi Yan

16:00 – 16:30 Presentation 6 eCEO:An eﬃcient Cloud Epistasis cOmputing model in genome-wide association study Zhengkui Wang

16:30 – 17:00 Prize presentation and photo taking List of Posters

1 CD155 Expression by TLR Agonists on Antigen-Presenting Cells Depends on NF-κB and IRFs ...... 14 Neha Kamran 2 Macromolecular Crowding & Stem Cell Differentiation ...... 15 Rafi Rashid, Michael Raghunath, Thorsten Wohland 3 The Characterization of D-Ptx1 and its Role in Drosophila Cell Fate Specification ...... 16 Joanne Toh, Murni Tio, Gerald Udolph 4 Integrating Multiple Signals in Immune Modulation ...... 17 Tan Suet Ting Rebecca, Ding Jeak Ling 5 Characterization and Long-term Homing Potential of Pregnancy Associated Progenitor Cells (PAPCs) in a Murine Model of Fe- tomaternal Microchimerism ...... 18 Yeo Ailing 6 Using Stem Cell-derived Insulin-producing Cell Lines to Delin- eate Unique Biological Pathways as Therapeutic Targets . . . . . 19 Ronne Yeo Wee Yeh, Lim Sai Kiang 7 Identification and Characterization of the Vertebrate Motile Cil- iome ...... 20 Deepak Babu 8 An Analysis of a Pak4 Signaling Complex ...... 21 Widyawilis Selamat, Edward Manser 9 A Novel Anticoagulant from Amblyomma variegatum (Tropical Bont Tick) ...... 22 Angelina Tan, Maria Kazimirova, RM Kini 10 CENTDIST: Discovery of Co-associated Factors by Motif Distri- bution ...... 23 Chang Cheng Wei, Zhang Zhizhuo, Goh Wan Ling, Cheung Chong Wing, Sung Wing King 11 Structural and Functional Study of a Spider Silk Protein-AcSp1 . 24 Wang Shujing 12 Natural Variant Forms of C1q ...... 25 Leong Jing Yao 13 Development of Living Color Transgenic Medaka for Biomonitor- ing Aquatic Contamination ...... 26 Ng Hwee Boon Grace 14 EvpP is a Unique Protein in T6SS of E. tarda ...... 27 Hu Wentao 15 Novel Approaches for the Identification of Viral Epitopes Asso- ciated with Asian HLA Employing Conditional Ligands . . . . . 28 Cynthia Xin Lei Chang, Ming Yan Or, Kai Yee Toh, Anthony T Tan,

iv Adeline Siew Eng Chia, Melissa Hui Yen Chng, Hsueh-Ling Janice Oh, Yee-Joo Tan, Antonio Bertoletti, Gijsbert M Grotenbreg 16 Novel Antibodies against Virulence Factors of the Type VI Se- cretion System in Burkholderia pseudomallei ...... 29 Lim Yan Ting, Paul A MacAry, Gan Yunn Hwen 17 Altered Cellular Iron Metabolism During Senescence in IMR-90 Fibroblasts ...... 30 Hendry S. Cahaya, David W. Killilea, Sebastian Schaffer, Bruce Ames, Barry Halliwell 18 Live Ratiometric Ca2+ Imaging in a Zebrafish Model of Spinal Muscular atrophy ...... 31 Kelvin See, Christoph Winkler 19 PRL-3 phosphatase downregulates beta-catenin, a Wnt-signalling component, in vitro and in vivo ...... 32 Abdul Qader Al-aidaroos, Wang Hai He, Zeng Qi 20 EGF signaling pathway involvement in regulating keratin dynamics in an Epidermolysis Bullosa Simplex disease model ...... 33 Tong San Tan, John E.A. Common, Cedric Badowski, E. Birgitte Lane 21 Cell Cycle Lipidomics ...... 34 Jing Yan Lim, Markus Wenk 22 Synthesis of Heterometallic Cobalt Clusters and Their Magnetic Properties ...... 36 Pei Wang and T.S. Andy Hor 23 Mechanism of Hydrogen Peroxide Induced Keratinocyte Cell Sheet Migration ...... 37 Loo Eng Kiat, Alvin, Ho Rongjian, Wong Yee Ting, Barry Halliwell 24 Targeting the “Turtle” – Metabolic Labelling of Inositol lipids . . 38 Shareef Mohideen Ismail, Sandip Pasari, Martin Lear, Markus Wenk 25 Designing Artificial Team-mates for Increased Affiliation . . . . . 40 Tim Merrit, Kevin McGee 26 Rereadability in Procedural Hypertext Fiction ...... 41 Alex Mitchell 27 State Space Reduction for Linearizability Checking ...... 42 Zhang Shaojie 28 Non-negative Matrix Factorization with KL Divergence Criterion Equals Maximum Likelihood Decomposition ...... 43 Wang Xuancong, Sim Khe Chai 29 Domain Adaptation for Semantic Role Labeling in the Biomedical Domain ...... 44 Daniel Dahlmeier, Hwee Tou Ng 30 SOPRAN: Scalable Online Proactive Re-optimization in Virtual Machine Management with Dynamic Workloads ...... 45 Jian Zhou, Lei Shi, Kian-Lee Tan 31 Mesoporous Poly-Melamine-Formaldehyde for Reversible Carbon Dioxide Adsorption ...... 48 Mei Xuan Tan, Yugen Zhang, Jackie Y. Ying 32 Surface-Functionalized and Surface-Functionalizable Poly(vinylidene fluoride) Graft Copolymer Membranes via Click Chemistry and Atom Transfer Radical Polymerization ...... 49 Cai Tao, Kang En-tang 33 Electrospun Nanofibrous Composite for Osteogenic Differentia- tion of Mesenchymal Stem Cells ...... 50 Luong T. H. Nguyen, Susan Liao, Seeram Ramakrishna, Casey K Chan 34 Biological Adhesives as Initiator Anchors for Surface-initiated Polymerization in the Preparation of Multifunctional “Green” Surfaces ...... 51 Wenjing Yang, Gary H. Dickinson, Serena Lay-Ming Teo, Tao Cai, Koon-Gee Neoh, En-Tang Kang 35 Nonlinear Control of Underactuated Systems With Applications to Autonomous Robotics ...... 52 Guo Zhaoqin 36 Analysis and Control of Closed Quantum Systems Based on Real- valued Dynamics ...... 53 Xue Zhengui, Lin Hai, Lee Tong Heng 37 A Real-time Reconstruction Approach for AR-based Applications 54 Jiang Shuai, Ong Soh Khim, Andrew Y. C. Nee 38 Image Correlation Spectroscopy as a Tool for Microrheology of Soft Materials ...... 55 Nicholas Agung Kurniawan, Chwee Teck Lim, Raj Rajagopalan 39 Metabolic Networks Based Approach for Understanding Struc- tural Organization Principles of Essential Genes ...... 56 Ma Jing 40 Toxicant-induced Sexual Dimorphic Responses in Zebra Fish Metabolic System ...... 57 Zhang Xun 41 Remote Maintenance using Augmented Reality Technology . . . 58 Zhu Jiang, Andrew Yeh-Ching Nee, Patricia Soh-Khim Ong 42 Augmented Reality 3D Design Space ...... 59 Ng Lai Xing 43 Electrophysiological consequence of genetic perturbation in gastrointestinal diseases — a computational investigation ...... 60 Poh Yong Cheng, Martin Buist

44 Magnetism and Magnetotransport Studies in Ge0.9Mn0.1Te . . . 61 Lim Sze Ter, J. F. Bi, K. L. Teo, and T. Liew 45 Multi DOF Active Vibration Isolation and its Application in Pre- cision Pointing of Flexible Spacecrafts ...... 62 Liu Lei, K K Tan, S Huang, T H Lee 46 Morphological Tuning, Self-assembly and Optical Properties of Indium Oxide Nanocrystals ...... 63 Zhang Shuangyuan, Ye Enyi, Han Mingyong 47 Genome-scale Modeling and in silico Analysis of Pichia pastoris for Biotechnological Applications ...... 64 Chung Kai Sheng, Bevan, Lee Dong-Yup 48 Quantitative Analysis of Surface Pluripotent Marker Expression on Human Embryonic Stem Cells (hESCs) during Differentiation Using hESC - Specific Antibodies ...... 65 Lesley Y Chan, Evelyn KF Yim, Andre B Choo 49 Hybrid Control for Unmanned Helicopters ...... 66 Ali Karimoddini, Lin Hai, Ben Chen, T. H. Lee 50 Soft Tissue Discrimination in Magnetic Resonance Elastography Using a New Elastic Level Set Model ...... 67 Li Bing Nan, Chui Chee Kong, Ong Sim Heng, Numano Tomokazu, Washio Toshikatsu, Kobayashi Etsuko 51 Design and Engineering of Cellulose Ester Membranes for For- ward Osmosis ...... 68 Zhang Sui, Wang Kai Yu, Chung Tai-Shung, Y. C. Jean, Chen Hong- min 52 Polyelectrolyte Microcapsules for in Vitro Delivery of Basic Fi- broblast Growth Factor ...... 69 Zhen She 53 Semi-interpenetrating Network (SIPN) Proton Exchange Mem- branes Based on Poly(2,6-Dimethyl-1,4-Phenylene Oxide) . . . . 70 Fang Chunliu 54 Regulation of Cullin RING E3 Ubiquitin Ligases by CAND1 In Vivo ...... 72 Boon Kim Boh, Yee Shin Chua, Wanpen Ponyeam, Thilo Hagen 55 Functional Effects of a Novel BIM Polymorphism in Mediating Resistance to Tyrosine Kinase Inhibitors in Chronic Myelogenous Leukaemia ...... 73 Juan Wen Chun, Ng King Pan, Ko Tun Kiat, Axel Hilmer, Charles Chuah Thuan Heng, Ruan Yijun, Ong Sin Tiong 56 Regulation of C1q Expression at Transcriptional and Epigenetic Levels ...... 74 Tan Shurong Carol, Lu Jinhua 57 Structural Refolding of Hepatitis B Virus X Protein (HBx) . . . 75 Oh Man Huan Veronica, Ren Ee Chee 58 Identification and Functional Analysis of AP2γ as a Novel Tran- scriptional Cofactor of Estrogen Receptor α in Breast Cancer . . 76 Si Kee Tan, Zhen Hua Lin, Cheng Wei Chang, Kern Rei Chng, Eu Leong Yong, Edwin Cheung 59 Understanding the Regulatory Network of Androgen Receptor and TMPRSS2-ERG Fusion Protein in Prostate Cancer Progression 77 Chng Kern Rei, Tan Si Kee, Chang Cheng Wei, Yang Chong, Hong Shuzhen, Edwin Cheung 60 Bcl-2 Modulates Resveratrol-induced ROS Production by Regu- lating Mitochondrial Respiration in Tumor Cells ...... 78 Ivan Cherh Chiet Low, Shazib Pervaiz 61 A Novel Role for RUNX3 in the Regulation of IL23A ...... 79 Yit Teng Hor, Dominic Voon Chih Cheng, Jason Koo Kin Wai, Huajing Wang, Yoshiaki Ito 62 Characterization of the Role of E7 in Transcriptional Regulation of Mitotic Genes ...... 80 Pang Chai Ling, Teissier Sebastien, Thierry Francoise 63 Identification of Recurrent Regions of Copy Number Variants Across Multiple Individuals ...... 81 Teo Shu Mei, Agus Salim, Yudi Pawitan 64 Dengue Virus Neutralization in Human Monocytes ...... 82 Chan Kuan Rong, Zhang Li-Xin, Tan Hwee Cheng, Brendon Hanson, Mariano A Garcia-Blanco, Ooi Eng Eong 65 Sustained High Levels of IL-6 Contribute to the Pathogenesis of Enterovirus 71 in a Neonate Mouse Model ...... 83 Khong Wei Xin, Damian G. W. Foo, Tan Eng Lee, Sylvie Alonso 66 Role of Rac1 in Regulating Bcl-2 Mediated Chemoresistance and Pro-oxidant State in Tumour Cells ...... 84 Kang Jia, Rathiga Velaithan, Jayshree L. Hirpara, Catherine Brenner, Marie Veronique Clement, Shazib Pervaiz 67 Study on Wrinkly Skin Syndrome (WSS) using induced Pluripo- tent Stem Cells (iPSCs) model ...... 85 Zhou Fan, Zhang Jinqiu, Nathalie Escande-Beillard, Bruno Reversade, Fu Xinyuan, Alan Colman 68 Quasi-Freestanding Epitaxial Graphene on SiC via Fluorine In- tercalation from a Molecular Source ...... 88 Wong Swee Liang 69 Structure and Mechanical Properties Study of Bombyx Mori Silk- worm Silk Fibrils by Atomic Force Microscope and X-ray Diffraction 89 Deng Qinqiu 70 Nanoparticles Fractionation using Aligned Carbon Nanotube Array 90 Xiaodai Lim, Hairuo Xu, Yi Hui Nicole Chew, Yi Hui Phua, Edbert Jarvis Sie, Tze Chien Sum, Guo Hao Chia, Wee Shong Chin, Chorng- Haur Sow 71 Experimental and Computational Studies of Fibroblast Migra- tion on Compliant Substrates ...... 91 Yip Ai Kia, Chiam Keng Hwee, Paul Matsudaira 72 Dynamic-based Structure Measures on Complex Networks . . . . 92 Zhu Guimei, Li Baowen Welcome to the 3rd NGS student symposium

Li Baowen

The NGS symposium is a great platform for NGS students to exchange their research results and novel ideas with fellows from other disciplines, and with senior scientists. We are living in an era of many cutting edge technologies and scientific discoveries, borne from interactions among scientists and engineers from different disciplines and backgrounds. Much of the most exciting research lies in the intersecting areas of different fields. Distinguished scientists and engineers are very often valuable role models and resources of inspiration for young researchers. This year, we are very pleased to have two distinguished Professors to share their research with NGS students: Prof. Anthony Zee from the University of California, Santa Barbara and Prof. Ding Jeak Ling from NUS. Their successful stories in different disciplines will definitely give you encouragement and motivation to cross boundaries to explore new territories. Prof. Zee is a theoretical physicist trained in Princeton (B.Sc) and Harvard (Ph. D.). His research spans high energy physics, field theory, cosmology, biophysics, condensed matter physics and mathematical physics. Moreover, as described by himself: “Even Shakespeare likes my writing style”, his budding career is a writer. He has published several popular science books including “Swallowing Clouds”, “Fearful Symmetry”, and “An Old Man’s Toy”. His motto is “It is often deeper to know why something is true rather than to have a proof that it is.” He is a classical example showing that you cannot only excel in your primary research field, but also express your passion in other beloved fields. Prof. Ding Jeak Ling, a Provost Chair Professor at Department of Biological Science, NUS, has been working in innate immunity and host-pathogen surveillance strategies for many years. Because of her outstanding research, she has been awarded numerous awards including 1995 NSTB Award for outstanding research, 2000 Far Eastern Economic Review Award for Outstanding Research, 2001 and 2008 NUS Outstanding Researcher Award. All of these and her many activities in NGS and NUS have made her an excellent mentor. Complementing these keynote talks, I am sure that you will equally enjoy all the students’ talks from the diverse disciplines presented in this symposium.

Li Baowen Professor of Physics Executive Director NUS Graduate for Integrative Science and Engineering

1 Keynote Speaker Session 1

Anthony Zee

The importance of interdisciplinary perspective in theoretical physics

I will talk about the importance, in doing theoretical physics, of having a broad appreciation of the subject. The talk will draw upon historical developments as well as from my personal experience.

Curriculum Vitae Anthony Zee, 徐一鸿 , (born in Kunming in China) is a Chinese American physicist, writer, and currently a professor at the Kavli Institute for Theoret- ical Physics and the physics department of the University of California, Santa Barbara. Zee obtained his Ph. D. from Harvard in 1970. During 1970-72 and 1977-78, he was at the Institute for Advanced Study. From 1973 to 1978, he was an Alfred P. Sloan Fellow. In his first year as assistant professor at Prince- ton, Zee had Ed Witten as his teaching assistant and grader. Professor Zee has authored or co-authored more than 200 scientific publications and several books. He has written on particle physics, condensed matter physics, anomalies in physics, random matrix theory, superconductivity, the quantum Hall effect, and other topics in theoretical physics and evolutionary biology, as well as their various interrelations. His scientific publications have been cited more than 10,000 times, and his h-index is 54 as of 2006. Zee is an accomplished teacher, covering both general relativity and quantum field theory. The culmination of his teaching is his text Quantum Field Theory in a Nutshell. He is also the author of several books for general readers about physics and Chinese culture. http://en.wikipedia.org/wiki/Anthony Zee http://www.kitp.ucsb.edu/˜zee/index.php

2 Keynote Speaker Session 2

Ding Jeak Ling

Many Roads in Research – Reinvent oneself?

From basic to applied research; from bench to bedside, there are many roads leading to-and-from research. Do we fashion our research according to our hearts’ desire, to where the need is, or to where the funding source is focusing on? In this talk, I will give a flavor of different paths which I have threaded on- from basic to applied, and then back to fundamental research again. Sometimes the compass was driven by the research funding focus, but mostly the paths pursued have been based on my own bearing of fundamental research interest, albeit keeping alert to translational research, to capture any potential biotechnological gains. I will share my experiences on intellectual property protection and commercialization of research products, as well as publishing and not per- ishing. Often, we cannot predict the outcome, but a flexible, imaginative and accommodating mind can be most rewarding......

Curriculum Vitae Ding Jeak Ling is a Professor at the Department of Biological Sciences as well as the Provost Chair Professor of National University of Singapore. Her research interest is the frontline immune defense mechanisms during acute phase infection. Beside academic research, she is also a successful technopreneur, with two patents which have been commercialized by Lonza Inc and BioDTech Inc. She has also been awarded the Far Eastern Economic Review Award for outstanding research.

Position Held 1982-84 Postdoc. Res. Fellow, MRC Clinical Res. Centre, London, UK. 1985-88 Lecturer, Dept. of Zoology, NUS 1989-94 Senior Lecturer, Dept. of Zoology, NUS 1995-2001 Assoc. Prof., Dept. of Biological Sciences, NUS 2001- Professor, Dept. of Biological Sciences, NUS 2009- Provost Chair Professor, NUS

Major Research Interest: - Host-pathogen interaction, Innate immunity Frontline immune defense mechanisms in acute phase infection, e.g. (1) Mech- anisms of pathogen-interactome formation; (2) Transcriptional regulation of innate immunity; (3) Immune signaling and apoptosis; (4) Development of an-

3 timicrobials and anti-inﬂammatory therapeutics.

Patents & Commercialisation

• Ding JL and Ho B (1998, 1999, 2001, 2002) – Cloning and expression of horseshoe crab Factor C for detection, removal of endotoxin & endotoxin therapeutics (US Patents); PyroGene commercialised by Lonza Inc.; LPS- binding Sushi peptides for depyrogenation commercialised to BioDTech Inc., USA. • Ding JL, Tan NS, Ho B and Lam TJ (1998) – Isolated nucleic acids en- coding a secretory signal for expression and secretion of heterologous recombinant proteins (US Patent granted).

Recent Administrative positions 2005-2007 Member, UPTC 2007-2010 Dy. Chair, University Research Council Grant Committee (Biomedical Engnr. Life Sci.) 2006-2010 NUS-YIA (Young Investigator Award) Panel member 2007-2009 Member, NGS “Senior Advisory Committee on Graduate Education” (SAGE) 2008- Member & Ag Chair, FPTC 2010- Chair, NGS Snr. Advisory Committee for Graduate Education (SAGE) Member, NGS EXCO 2010-2012 Member, Singapore Medical Council’s Complaints & Disciplinary Panel

Selected Awards 1995 NSTB award for outstanding research in genetic engineering 2000 Far Eastern Economic Review Award for outstanding research 2001 NUS Outstanding Researcher Award 2008 NUS Outstanding Researcher Award 2009 Provost Term Chair Professorship Oral Presentations

5 PRESENTATION 1

A Universal Relation between Heat Conduction and Diﬀusion

Liu Sha1, Li Baowen1 1Center for Computational Science and Engeering, Department of Physics

We rigorously prove a useful equality relating the heat current autocorrelation function and the mean square displacement of the energy diffusion. From this equality, we are able to recover the existing theories for normal diffusion and normal heat conduction. Moreover, we are also able to obtain a connection between anomalous diffusion and anomalous heat conduction. Our results are applicable to all isotropic systems with any dimension.

6 PRESENTATION 2

Automated Aesthetic Enhancement of Videos

Xiang Yangyang1, Mohan Kankanhalli2 1NUS Graduate School for Integrative Sciences and Engineering 2School of Computing

We present a content based single-shot video editing scheme. We follow the classic long take directing and editing schemes. This system automatically ad- justs the projection velocity of raw video clips to enhance the aesthetic interest. We build up the mathematical model for projection rhythm manipulation based on film theories. The system segments interesting sub-shots and ordinary sub- shots within the single video clip. Different sub-shots are projected to different duration to maximize the video interest. The output video is rendered according to adjusted projection duration. Within this framework, we transform the screen rhythm and camera motion of a given single video shot. Motion inter- ests of frames are re-distributed in projection duration modification and certain special projection patterns are introduced to enhance the aesthetic interest of original video. The user study shows that our scheme is very effective.

7 PRESENTATION 3

Development of an Health Monitoring System for the Elderly

Yuan Jian1, Kok Kiong Tan1, Tong Heng Lee1 1Department of Electrical and Computer Engineering

This paper describes the development of a low-cost health monitoring system for the elderly at home. The system integrates ZigBee mesh network, cellular network, ubiquitous and mobile computing, hardware miniaturization and various sensor technologies. The centerpieces are wearable devices that are capable of detecting accidental falls, monitoring heart rate, tracking locations, etc. The wearable devices are modular so that certain sensors can be added in a plug-and-play fashion. Wearable devices communicate with the Base Station centered at home via ZigBee mesh network. The base station is integrated with a GSM module. Vital signs and health status sent from wearable devices will be forwarded to caregivers’ mobile phones in real time via SMS. Meanwhile, caregivers are able to query status and even initiate basic diagnosis via SMS in case of emergency. The paper will focus on hardware and software architectures as well as low power design for data acquisition and signal processing in wireless sensors.

8 PRESENTATION 4

Building 3D Tissue Structures With Polyelectrolyte Fibers

Toh Kah Chin Jerry1,2, Leong Meng Fatt1, Andrew Wan1, Jackie Y. Ying1 1Institute of Bioengineering and Nanotechnology 2NUS Graduate School for Integrative Sciences and Engineering

Polyelectrolyte fibers consisting of chitin and alginate have been known to be amenable to cell encapsulation due to their aqueous, mild pH, room temperature synthesis. A large variety of encapsulated cells show high viability within the polyelectrolyte based fibers, and proliferation, differentiation, alignment and aggregation of these cells has been observed. Examples of tested cells include human mesenchymal stem cells, human umbilical cord vascular endothelial cells, Madin Darby canine kidney cells and even primary hepatocytes derived from rat tissue. By using cell-laden polyelectrolyte fibers as building blocks, we have been able to pattern different cells in three dimensional niche environments in close proximity. The chemical and biological composition of each fiber can be individually tailored by varying the composition of the polyelectrolytes and bio- logics within the fiber. Typical three dimensional constructs assembled fashion fibers around a central axis. This allows us to create fiber constructs in a manner highly reminiscent of a liver sinusoid structure. Encapsulation of endothelial cells within this center fiber thus paves the way for directed angiogenesis, allowing us to overcome the major hurdle facing the creation of thick tissue engineered constructs that of the oxygen diffusion limit.

9 PRESENTATION 5

Linc-ing Neurogenesis – Long Non-coding RNAs Determine Neural Stem Cell Fate

Ng Shi Yan1, Lawrence. W. Stanton1 1Stem Cell and Developmental Biology, Genome Institute of Singapore

Long intervening non-coding RNAs (LincRNAs) constitute a large portion of the mammalian transcriptome, but their biological functions remain elusive. To date, only a handful of lincRNAs have been prescribed a biological role. Previous studies had shown that many lincRNAs are expressed in the developing nervous system in a spatially- and temporally-regulated manner, indicating that lincRNAs may play a part in neural development. In order to study the roles of lincRNAs in midbrain neurogenesis, we developed a two-step differentiation scheme in which a pure population of neural progenitors (NPCs) can first be derived from human embryonic stem cells (hESCs). In the second step, NPCs were subsequently differentiated into dopaminergic (DA) neurons with 80-85% efficiency. By means of a custom-designed non-coding microarray, we identified lincR- NAs that were highly expressed in NPCs and DA neurons compared to the undifferentiated hESCs. To investigate if these lincRNAs are functional, knockdown of some of these transcripts were performed in a human neural stem cell line, and their ability to differentiate into neurons was assayed. The silencing of three lincRNAs assayed resulted in an inhibition of neurogenesis, indicating that these lincRNAs are required for the differentiation of neurons. Using in-vitro transcribed biotinylated lincRNAs, we sought to determine the mechanisms of neuronal gene activation brought about by these neural-specific lincRNAs.

10 PRESENTATION 6

eCEO:An eﬃcient Cloud Epistasis cOmputing model in genome-wide association study

Zhengkui Wang1, Yue Wang1, Kian-Lee Tan2, Limsoon Wong2, Divyakant Agrawal3 1NUS Graduate School for Integrative Sciences and Engineering 2School of Computing 3Department of Computer Science, University of California, Santa Barbara, USA

A large number of single nucleotide polymorphisms (SNPs) have been provided for genome-wide association studies. Discovering the epistatic interactions of SNPs in this large number of SNPs has become very important and challenging. Recent studies suggested that the combination of multiple SNPs could have more significant associations with a specific phenotype. However, the computational difficulty has become the main bottleneck for large scale identification of such epistatic interactions of SNPs. In this paper, we propose an efficient Cloud- based Epistasis cOmputing (eCEO) model for large scale epistatic interaction which can be run both on any affordable PC-based cluster or cloud computing platforms in GWAS. We provide efficient and feasible solutions to the two main computational difficulties in discovering the significant association between the combination of multiple SNPs and phenotypes in large scale data sets.

Poster Presentations: Biology

13 POSTER 1

CD155 Expression by TLR Agonists on Antigen-Presenting Cells Depends on NF-κB and IRFs

Neha Kamran1 1Immunology Programme, Department of Microbiology

CD155 is a ligand for the activating receptor DNAM-1, which is constitutively expressed on most immune cells. It is expressed at low levels in healthy tissue and is often up-regulated in tumor cells. Binding of CD155 to DNAM-1 induces NK cell and CD8+ T cell-mediated cytotoxicity and cytokine secretion. Apart from its role as an immune cell activating ligand, CD155 serves as an adhesion molecule and also mediates the migration of leukocytes through blood vessels. In addition interaction of CD155 with TIGIT can also lead to the suppression of immune system and induction of tolerance. Although the functions of CD155 have been well characterised, the mechanisms inducing CD155 expression are yet to be elucidated. To address this question we looked at danger signals such as Toll like receptor activation. Here we show that CD155 is induced by Toll Like Receptor (TLR) stimulation on professional antigen presenting cells. TLR mediated up-regulation of CD155 is MyD88 and TRIF dependent. In addition our data show that NF-ØB and IRF family members are involved in regulating the induction of CD155 expression in response to TLRs. Overall the data indicates that CD155 serves as a “danger signal” sensor alerting the immune system to the presence of diseased cells.

14 POSTER 2

Macromolecular Crowding & Stem Cell Diﬀerentiation

Raﬁ Rashid1,2, Michael Raghunath3,4,5, Thorsten Wohland2,6 1NUS Graduate School for Integrative Sciences and Engineering 2NUS Centre for Bioimaging Sciences 3Department of Biochemistry, Yong Loo Lin School of Medicine 4Division of Bioengineering 5NUS Tissue Engineering Programme 6Department of Chemistry

Macromolecular crowding (MMC) is a biophysical tool which has been used extensively to enhance chemical reactions and biological processes by means of the excluded volume effect (EVE). Macromolecular crowding is known to be an important feature of cells as it governs all biochemical reactions. The cytoplasm and organelles, such as the mitochondria and nucleus, are crowded with small solutes, soluble macromolecules, cytoskeletal proteins and membranes. Cell membranes are also crowded with lipid and protein molecules. One biological application of crowders is the enhancement of the differentiation of human mesenchymal stem cells (hMSCs) into the adipogenic lineage. We have postu- lated that these crowders bring about biological effects by changing diffusion rates on the cellular plasma membrane. In order to fully understand the effects of crowders on cells, we have measured the diffusion of fluorophores of various sizes in solutions of several crowder species over a wide concentration range by fluorescence correlation spectroscopy (FCS). We have also performed measurements on supported lipid bilayers and cellular membranes in the presence of crowder molecules using FCS. The data presented here suggest that crowding agents such as Ficoll 70 kDa, Ficoll 400 kDa and dextran 70 kDa can affect diffusion via changes in viscosity, but it is still not clear whether or not excluded volume effects are present as well. The confocal-FCS measurements do not show that the Fc70/Fc400 mixture (which is used to potentiate differentiation of stem cells) is having any direct effect on membrane dynamics. However, in the cellular context, it is possible that crowders are producing effects via other mechanisms. We also show here that, contrary to popular belief, crowders are not inert and are capable of entering the cytoplasm of cells. New experiments are needed to determine any possible connection between crowder uptake (or excluded volume) and the enhanced differentiation of stem cells.

15 POSTER 3

The Characterization of D-Ptx1 and its Role in Drosophila Cell Fate Speciﬁcation

Joanne Toh1,2, Murni Tio2, Gerald Udolph2 1NUS Graduate School for Integrative Sciences and Engineering 2Institute of Medical Biology, Agency for Science Technology and Research

The fruit fly Drosophila provides an ideal model system to study the function of genes that control neurogenesis, allowing us to understand the mechanisms that generate and pattern the nervous system. Homeodomain-containing transcription factors are known to act in combination to specify different neuronal identities or neuronal subtypes. Here, we characterize a paired-type homeobox gene, D-Ptx1, which is a Drosophila homolog of the Pitx family. D-Ptx1 was first observed to be expressed in segmentally repeated patterns in embryonic central nervous system and in a subset of muscles. D-Ptx1 expression can also be found in the larval brain lobes and the ventral nerve cord (vNC) where it is expressed in some neurons. Functional characterization of D-Ptx1 mutants revealed defects in the axonal projections in the vNC and the peripheral nervous system (PNS). We also observed gain or loss of neurons, indicating that D-Ptx1 might play roles in neuronal cell fate specification. Knockdown of D-Ptx1 using siRNA technology demonstrated that D-Ptx1 is required during embryonic and larval neurogenesis particularly in axonal pathfinding as well as during myoge- nesis. Interestingly, Tyrosine Hydroxylase (TH) expression was partially lost in the larval vNC, suggesting that D-Ptx1 may be needed for larval dopaminergic neurons. Over expression studies of D-Ptx1 revealed defects in the PNS as well as in the vNC. Taken together, we hypothesize that D-Ptx1 is required for some aspects of neuronal differentiation. Further studies are required to understand the molecular mechanisms of D-Ptx1 function during nervous system development.

16 POSTER 4

Integrating Multiple Signals in Immune Modulation

Tan Suet Ting Rebecca1,2, Ding Jeak Ling1,2 1Department of Biological Sciences 2NUS Graduate School for Integrative Sciences and Engineering

Early research on TLR-mediated signaling has focused on the effects of single ligands and their receptors. However, a single pathogen contains multiple pathogen-associated molecular patterns (PAMPs) and is likely to engage multiple pathways simultaneously. Innate immune cells employ a range of receptors to detect specific PAMPs (e.g. TLR, NLR, RLR), integrating these individual signals in order to mount an appropriate response. Here, we have found that certain combinations of TLR ligands cause a much greater response than when the ligands are administered singly, a phenomenon described as synergy. In particular, we have shown that the combination of poly I:C (TLR3 or RIG-I) and R848 (TLR7/8) is highly synergistic for proinflammatory cytokines such as IL-6 and IL-12p40. Other than the combination of PAMPs, synergy is strongly influenced by the timing of stimulation. Two main classes of cytokine behaviour have been observed, showing optimal synergy either upon simultaneous stimulation or when the second stimulation is administered 8 h after the first. Taken together, these data show that the innate immune system discriminates between different combinations of PAMPs and the response mounted is highly context dependent.

17 POSTER 5

Characterization and Long-term Homing Potential of Pregnancy Associated Progenitor Cells (PAPCs) in a Murine Model of Fetomaternal Microchimerism

Yeo Ailing1 1Institute of Medical Biology

Bidirectional cell trafficking between fetus and mother during pregnancy is a well-established phenomenon observed in placental vertebrates. Although studies have shown that transmigratory fetal cells, also termed pregnancy-associated progenitor cells (PAPCs), can integrate into multiple maternal organs, the integration, and differentiation of PAPCs in organs such as the brain has not been extensively studied. Particularly, there is a lack of data on the long term presence as well as the temporal dynamics of PAPCs in healthy mothers. To determine the long term engraftment potential of PAPCs in healthy mothers, the presence of GFP+ PAPCs within a panel of maternal organs was studied. Us- ing qPCR and FACS, PAPCs were observed in the maternal circulation as early as E12.5 but numbers decreased immediately after delivery. Despite the lack of cells in the peripheral blood postpartum, PAPCs could be found in multiple maternal organs up to 7 months post partum. This suggested long-term homing capabilities of PAPCs which raised the question whether PAPCs were able to integrate and differentiate into organ-specific cell types. To answer this question, the differentiation capability of PAPCs in the maternal brain was studied using Thy1-YFP mouse model. PAPCs were found to adopt neuronal cell fates in multiple brain regions. It was demonstrated that PAPCs underwent neuronal maturation in the hippocampus and the results also indicated that mechanisms of neuronal maturation of PAPCs could be similar to that described in adult neurogenesis. Future research will focus on the further characterization of PA- PCs as well as uncovering their fetal origin.

18 POSTER 6

Using Stem Cell-derived Insulin-producing Cell Lines to Delineate Unique Biological Pathways as Therapeutic Targets

Ronne Yeo Wee Yeh1, Lim Sai Kiang1 1Institute of Medical Biology, Agency for Science Technology and Research

To identify unique biochemical pathways in embryonic stem cell-derived insulin- producing cells as potential therapeutic targets to prevent or delay beta cell dysfunction or death in diabetic patients, comparative genome-wide gene expression studies of recently derived mouse insulin-producing cell lines and their progenitor cell lines were performed using microarray technology. Differen- tially expressed genes were functionally clustered to identify important biochemical pathways in these insulin-producing cell lines. Biochemical or cellular assays were then performed to assess the relevance of these pathways to the biology of these cells. 185 genes were highly expressed in the insulin- producing cell lines and computational analysis predicted pentose phosphate pathway (PPP), clathrin-mediated endocytosis and the peroxisome proliferator- activated receptor (PPAR) signaling pathway as important pathways in these cell lines. Insulin-producing ERoSHK cells were more resistant to hydrogen peroxide (H2O2)-induced oxidative stress. Inhibition of PPP by dehydroepiandros- terone (DHEA) and 6-aminonicotinamide (6-AN) abrogated this H2O2 resistance with a concomitant decrease in PPP activity as measured by MTT assay. Clathrin-mediated endocytosis which is essential in maintaining membrane homeostasis in secreting cells was upregulated by glucose in ERoSHK but not in their progenitor ERoSH cells. Its inhibition by chlorpromazine at high glucose concentration was toxic to the cells. Troglitazone, a PPAR agonist, upregulated expression of Ins1 and Ins2, but not Glut2. Gene expression analysis has identified PPP, clathrin-mediated endocytosis and the PPAR signaling pathway as the major delineating pathways in these insulin-producing cell lines and their biological relevance was confirmed by biochemical and cellular assays.

19 POSTER 7

Identiﬁcation and Characterization of the Vertebrate Motile Ciliome

Deepak Babu1,2 1Department of Biological Sciences 2NUS Graduate School for Integrative Sciences and Engineering

Cilia and flagella are hair-like organelles with diverse roles in animal development, physiological homeostasis, and human health. While the function of these organelles is currently being investigated, little is known about the genes and gene networks underlying ciliogenesis. Previous work, from our group and oth- ers, has shown a master regulatory role for the winged-helix transcription factor Foxj1 in motile ciliogenesis. We have utilized this information to carry out a genome-wide microarray-based screen to identify the transcriptional targets of Foxj1. This is an endeavor to define and characterize all genes which have roles in ciliogenesis, ciliary structure and function. 548 genes with mammalian or- thologs were found to be up-regulated in response to over-expression of Foxj1 in zebrafish embryos. We further validated the array results by performing RT- PCR on a random subset of 55 genes. To characterize novel genes from the collection, we are carrying out systematic gene knock-down using morpholino oligonucleotides, and assaying for perturbations in ciliary architecture as well as examining developmental and physiological read-outs of defective cilia such as alterations in left-right asymmetry. In addition, using GFP-tagged versions of the proteins encoded by the genes, we are performing localization studies with respect to the ciliary apparatus. Our findings thus far indicate that the screen has successfully identified a set of novel genes required for ciliary development and function. Based on our results in the zebrafish, we believe that these novel ciliary genes will help us to better understand the causes of human ciliopathies.

20 POSTER 8

An Analysis of a Pak4 Signaling Complex

Widyawilis Selamat1,2, Edward Manser1 1sGSK-NRP, Agency for Science Technology and Research 2NUS Graduate School for Integrative Sciences and Engineering

The RhoGTPases are critical proteins involved in signal transduction pathways that reorganize the actin cytoskeleton. The many effectors of Rho GTPases transduce these signals to the cytoskeleton by recruitment of adaptors, actin binding proteins or by activation of key protein kinases such as ROK, MRCK, PAK or MLK. Pak4 is a target of Cdc42 and conserved from Drosophila to man. In one report, Pak4 was found to bind to a previously unknown protein referred to as INCA, which plays a role in neural crest morphogenesis. INCA has no known domains based on homology searches other than a central 38 residue Inca-box’ that is well conserved among vertebrate Inca proteins. Interestingly, we identified a gene product related to Inca that can also bind Pak4. On this basis, the related protein is termed Maya (unpublished). In an effort to understand the function of Maya as well as the role of Pak4, interacting partners need to be elucidated. Using a yeast two-hybrid screen with full-length human Maya as bait, a potential binding partner of Maya is identified. Here, we discuss results that indicate that a tri-complex association is possible among Maya, Pak4 and another Maya-interacting protein. The localization of Maya is affected by co-transfection with either of its interacting proteins, of which one is able to influence actin reorganization. Therefore, I propose a model in which Pak4 could also be involved in the regulation of actin assembly through this tri-complex association, in which Maya acts as a molecular bridge.

21 POSTER 9

A Novel Anticoagulant from Amblyomma variegatum (Tropical Bont Tick)

Angelina Tan1, Maria Kazimirova2, RM Kini1,3 1NUS Graduate School for Integrative Sciences and Engineering 2Institute of Zoology, Slovak Academy of Sciences 3Department of Biological Sciences

The salivary glands of haematophagaous insects are a rich source of molecules with anti-inflammatory, anti-haemostatic and immune-modulatory functions. They act to counter the host defence system during feeding of blood of animals by the insects, with the salivary gland activity and saliva secretion increased throughout this period of time. Our interest lies in the identification and characterization of novel anticoagulants from the saliva of Amblyomma variegatum, commonly known as the tropical bont tick. Preliminary screening of salivary gland extracts from this tick has revealed the presence of anticoagulants, particularly, an inhibitor of factor Xa of the coagulation cascade. In an attempt to characterize this factor Xa inhibitor, we first sought to purify and isolate it through liquid chromatography. Anti-factor Xa activity was then detected by enzyme inhibition assays with a chromogenic substrate. Sequence and structure determination for functional studies is currently in progress. The aim of this project is to characterize this factor Xa inhibitor and study its structure-function relationship with factor Xa, in prospect of future development of potentially therapeutic drugs.

22 POSTER 10

CENTDIST: Discovery of Co-associated Factors by Motif Distribution

Chang Cheng Wei1, Zhang Zhizhuo2, Goh Wan Ling1, Cheung Chong Wing1, Sung Wing King5 1Genome Institute of Singapore, Agency for Science Technology and Research 2School of Computing

Transcription factors (TFs) do not function alone but work together with other TFs (called co-associated factors or co-TFs) in specific combinations to precisely control the transcription of target genes. Identifying the entire complement of co-TFs of a given TF will be an important step in understanding the transcriptional regulation mechanism. Existing methods predict co-TFs by counting the motif sites around ChIP-seq peaks. Their accuracy depends on whether the user can correctly supply the background model, the enrichment window size, and the PWM cutoff score for each motif. We have developed a novel application called CENTDIST, which does not require the input of any user-specific parameters. Instead CENTDIST uses information from the imbalanced distribution of binding sites for identifying co-TFs (http://compbio.ddns.comp.nus.edu.sg/˜chipseq/webseqtools/). Using this new statistical model, we correctly predicted all known co-TFs of AR in the prostate cancer cell-line LNCaP. We also discovered AP4 as a novel co- TF of AR. Furthermore, we tested CENTDIST on 13 ChIP-seq datasets for TFs in mouse embryonic stem cells and obtained results with similar success. Taken together, CENTDIST, a web-based program based on the imbalanced distribution of co-TF binding sites provides a user-friendly, parameter-less, and powerful predictive tool for understanding the co-regulation mechanism of TFs.

23 POSTER 11

Structural and Functional Study of a Spider Silk Protein-AcSp1

Wang Shujing1,2 1NUS Graduate School for Integrative Sciences and EngineeringNGS 2Department of Biological Sciences

Spider silk is high performance protein-based fibre, which has attracted human interest for thousands of years. AcSp1 protein, which can form aciniform silk, is reported to assemble into the small diameter fibers of egg case sacs and wrapping silks and can also construct web decorations and build sperm webs. Aciniform silk has been reported to be of the highest toughness among all the spider silks studied and current studies show that soluble domains of AcSp1 contain mainly α-helices and random coils, while conformation and orientation study of natural silk indicates it contains both α-helices and β-sheets. To further understand the molecular mechanism of spider silk formation and explain the specificity of AcSp1, the tertiary structure of each domain and the domain-domain interaction studies come to be the first choice using recombinant AcSp1 proteins. Our study starts from the most elementary soluble structure determination of different domains of AcSp1 by NMR, and, based on which, we study the interaction of different domains using different domain construct, aiming to provide hints on the AcSp1 silk-formation mechanism elucidation. Also, AcSp1 silk miniature study in vitro is of great importance for large scale artificial silk-like material production.

24 POSTER 12

Natural Variant Forms of C1q

Leong Jing Yao1 1Microbiology Department

C1q is a macromolecular complex composed of 18 polypeptide chains, composed of 3 fundamental chains (C1q A, B and C). C1q is implicated in several diseases such as Systemic Lupus Erthymatosus (SLE), artherosclerosis, Alzheimer disease, Prion disease and Antibody Dependent Enhancement (ADE) phenomenon in the flavivirus family (e.g Dengue, West Nile virus). It is interesting to note that in many of the disease implicated, C1q plays a protective role in delaying the onset in the early phase of the disease, however in the later phase of the disease, it plays a pathogenic role. Essentially, C1q plays a pathogenic role by activating the classical pathway of complement activation, resulting in the creation of an inflammatory environment (e.g recruiting immune cells), and on the reverse side of the coin, plays a protective role by enhancing the clearance of cellular debris (e.g apoptotic cells). Investigation into the secreted forms of C1q from important immune regulatory/phagocytic cells such as dendritic cells and macrophages in this project, revealed that a different form of C1q exists (termed as Low molecular weight or LMW). This LMW C1q was shown to exhibit a lower ability to active the classical pathway of complement activation and was able to enhance clearance of apoptotic cells. This seems to indicate that the dual nature (protective/pathogenic) of C1q could be better regulated by secreting the different forms of C1q. A methodology of purifying the LMW C1q from human serum was devised, and the protein now is under intense investigation for its functional properties.

25 POSTER 13

Development of Living Color Transgenic Medaka for Biomonitoring Aquatic Contamination

Ng Hwee Boon Grace1,2 1Department of Biological Sciences 2NUS Graduate School for Integrative Sciences and Engineering

With the advent of GFP reporter gene, it is feasible to apply the living color transgenic fish in monitoring water contamination. We report the generation of two biomonitoring transgenic medaka lines using a stress-inducible promoter, hsp70 and xenobiotic inducible promoter, cyp1a1 with the designation of Tg(hsp70:gfp) and Tg(cyp1a1:gfp) respectively. The transgenic lines were generated with the aid of maize Ac/Ds transposon system. Most founders screened were positive for germline transmission, thus indicating a high efficiency of the Ac/Ds system to aid transgene integration. Induction of GFP expression in Tg(hsp70:gfp) by heat shock treatment at 37◦C and heavy metals such as mercury, copper and cadmium demonstrate the inducibility of hsp70 promoter. Interestingly, specific heavy metals invoke certain GFP expression patterns in various organs of the embryos. Thus the newly developed transgenic line may be useful for monitoring stresses caused by heavy metals and may establish a pattern database to specify types of heavy metal insults. As for Tg(cyp1a1:gfp), GFP expression was observed in liver when treated with xenobiotic compounds such as Benzo[α]pyrene(BAP) and it was also observed in other organs such as kidney and gut during 2,3,7,8-Tetrachlorodibenzo-p-dioxin(TCDD) treatment, indicating its potential use to monitor polyaromatic hydrocarbon(PAH) con- taminations. In future we will characterize Tg(hsp70:gfp) and Tg(cyp1a1:gfp) with various categories of aquatic pollutants to determine their responsiveness and sensitivity.

26 POSTER 14

EvpP is a Unique Protein in T6SS of E. tarda

Hu Wentao1 1Department of Biological Sciences

Many gram negative bacteria utilize secretion systems to deliver effectors and toxins into their environment or directly into their hosts. So far 7 of them have been discovered. Edwardsiella tarda is a gram nagetive bacterium which utilizes both Type III and Type VI secretion systems to infect fish. EvpP is a unique effector from its Type VI Secretion System (T6SS). It has no homologue across different species that possess a T6SS. Previous study shows that knocking out EvpP hinders bacterial secretion of E. tarda. Yet so far, the structure as well as the exact function of EvpP still remains unknown. EvpP is a 20kD protein secreted together by T6SS with EvpC and EvpI. Current experiments show that EvpP and EvpC may have binding interaction. EvpP on its own is not very stable and tends to degrade to a 10kD piece over time. However it is resistant to common protease digestion. Only trypsin cuts EvpP and gives rise to a shorter piece also around 10kD. Interestingly N-terminal sequencing shows that the trypsin digested EvpP agrees with the self-degraded one. We are now trying to mass produce the shorter piece and solve its structure since this seems to be the rigid part of the whole protein. We will also investigate the function of EvpP after it gets secreted: whether it enters host cell or it stays just in the environment.

27 POSTER 15 Novel Approaches for the Identiﬁcation of Viral Epitopes Associated with Asian HLA Employing Conditional Ligands

Cynthia Xin Lei Chang1,2, Ming Yan Or1, Kai Yee Toh1, Anthony T Tan3, Adeline Siew Eng Chia3, Melissa Hui Yen Chng3, Hsueh-Ling Janice Oh4, Yee-Joo Tan1, Antonio Bertoletti3, Gijsbert M Grotenbreg1,2 1Department of Microbiology, Immunology Programme, Yong Loo Lin School of Medicine 2NUS Graduate School for Integrative Sciences and Engineering 3Singapore Institute for Clinical Sciences, Agency for Science Technology and Research 4Collaborative Anti-Viral Research Group, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research

The development of immunotherapies relies on valuable information regarding how the adaptive immune system recognizes and responds to infections. Specif- ically, epitopes presented by an appropriate class I Major Histocompatibility Complex (MHC) can induce a response from CD8+ T cells following recognition by its corresponding T cell receptor (TCR). The specificity of the immune response is dictated by the source of antigen, making the identification of pathogen-specific epitopes essential. The constellation of HLA restriction elements for each individual is a second determinant in antigen presentation, since genetic polymorphisms in the HLA influences peptide affinity for the gene product. For Asian variants of Human Leukocyte Antigen (HLA) little information on epitope specificity is currently available. CD8+ T cell epitope discovery can be achieved using recently developed high-throughput MHC enzyme-linked immunosorbent assay (ELISA) and MHC tetramer staining protocols. We therefore synthesized recombinant HLA class I molecules of allelic variants common in Asian populations, for example HLA-B*5801 and HLA-B*4001, complexed with ultra-violet (UV) light-sensitive conditional ligands. After UV irradiation, the cleaved ligand can be replaced by a peptide of choice thereby producing a novel peptide-MHC (pMHC) complex. The peptide exchange efficiency can be determined using an ELISA that compares the ability of various peptides to rescue the MHC after UV-mediated cleavage of conditional ligand. Further- more, the peptide exchange technology allows for high-throughput production of MHC tetramer libraries for epitope discovery. We will present data that appropriate MHC tetramer staining for the direct identification of in vitro expanded antigen-specific CD8+ T cells is achievable. Employing these methods, we show the successful determination of HLA restriction and fine specificity of epitopes from Severe Acute Respiratory Symptoms (SARS) and Hepatitis B Virus (HBV) that are associated with Asian HLA variants. Acknowledgment: This work was supported by the NRF Research Fellowship (NRF2007 NRF-RF001-226)

28 POSTER 16

Novel Antibodies against Virulence Factors of the Type VI Secretion System in Burkholderia pseudomallei

Lim Yan Ting1,2, Paul A MacAry1, Gan Yunn Hwen3 1Department of Microbiology, Immunology Program 2NUS Graduate School for Integrative Sciences and Engineering 3Department of Biochemistry, Immunology Program

The type VI secretion system (TSSS) is the latest addition to the previous ﬁve categories of Gram-negative protein secretion systems. Evidence of its role as a potential virulence factor in several Gram-negative pathogens has been highlighted, and this system is also present in Burkholderia pseudomallei, the causative agent of meliodosis. Hence, there are practical reasons for generating immunological reagents for studying the system in depth, which could aid in the development of new therapies and/or diagnostics. Our lab has thus currently generated novel antibodies against interesting components of the B. pseudomallei TSSS, which have enabled improved understanding of the basic biology of the pathogen.

29 POSTER 17

Altered Cellular Iron Metabolism During Senescence in IMR-90 Fibroblasts

Hendry S. Cahaya2,3,4,5, David W. Killilea4, Sebastian Schaﬀer5, Bruce Ames1,4, Barry Halliwell5 1Department of Biochemistry, UC Berkeley 2Department of Molecular & Cell Biology, UC Berkeley 3NUS Graduate School for Integrative Sciences and Engineering 4Center for Nutrition and Metabolism, Childrens Hospital Oakland Research Institute 5Department of Biochemistry, Yong Loo Lin School of Medicine

Iron accumulates as a function of age in many tissues and is associated with age- related pathologies. Although the molecular basis of this change is unknown, it may be due to the loss of iron homeostasis at the cellular level. Thus, the regulation of iron homeostasis was investigated in primary cultures of human fibroblast (IMR-90) as a model of cellular senescence. Previously, total intracellular iron, as determined by inductively-coupled plasma spectrometry, increased exponentially in IMR-90 as a function of age in culture. Age-related iron accumulation was also found to follow a parallel relationship with the oxidative state of the cell. Interestingly, modulating intracellular iron levels by chronic treatment of ferrous iron-citrate or iron-chelators had no effect on senescence, suggesting that age-related iron accumulation is a consequence, not a cause of cellular senescence. Iron uptake is predominantly mediated by transferrin receptor (TfR). During high metabolic iron demand, the expression of TfR density increases. Despite sufficient iron level, TfR density increased with age as determined by immunocytochemistry and Western blot analysis. The level of ferritin also increased as with age, despite the normally inverse relationship of TfR and ferritin. Moreover, the level of redox active labile iron pool as measured by calcein fluorometry increased in tandem with cellular senescence. Thus, home- ostatic control of iron could be altered during cellular senescence. One possible mediator of this change could be attributed from oxidative stress, which can uncouple the activity of the iron response proteins that regulate the expression of TfR, ferritin and other key regulatory proteins. Age-related oxidative stress may drive intracellular iron accumulation in human cells and induce cellular dysfunction.

30 POSTER 18

Live Ratiometric Ca2+ Imaging in a Zebraﬁsh Model of Spinal Muscular atrophy

Kelvin See1,2, Christoph Winkler1,2 1Department of Biological Sciences 2NUS Graduate School for Integrative Sciences and Engineering

Spinal Muscular Atrophy (SMA) is a progressive neurodegenerative disease specifically affecting lower motor neurons in the spinal cord. Mutations in the ubiquitously expressed Survival Motor Neuron (SMN) gene, which encodes a protein implicated in snRNP assembly, is known as cause of this disease but detailed molecular mechanisms for the motor neuron specific phenotype are still unclear. Abnormal synaptic transmission and altered presynaptic Ca2+ levels have recently been reported in mouse models of SMA. Here, we have under- taken an approach of using live in vivo ratiometric Ca2+ imaging to serve as a non-invasive reporter for motor neuron function. Two novel zebrafish stable transgenic lines have been established which make use of a FRET based Ca2+ sensor to detect changes in intracellular Ca2+ levels in CaP motor axons and in cells surrounding the CaP axons respectively. In one transgenic line, it was unexpectedly found that the sensor was expressed in cells surrounding the CaP axon. These cells express sox10 and are likely to be immature Schwann cells, which eventually differentiate to form the myelin sheath around the motor axon. Preliminary results from this line show that there is a significant reduction in Ca2+ influx into these glia cells during synaptic transmission in SMN morphant zebrafish embryos compared to uninjected controls. This suggests that the function of glia around the motor axons in regulating synaptic transmission may be affected in SMA. These novel transgenic lines may serve as a platform to assess motor neuron activity or glia excitability in live zebrafish and may be extended to research in other motor neuron degenerative diseases and neurobiology.

31 POSTER 19

PRL-3 phosphatase downregulates beta-catenin, a Wnt-signalling component, in vitro and in vivo

Abdul Qader Al-aidaroos1,2, Wang Hai He1, Zeng Qi1,3 1Institute of Molecular and Cell Biology, Agency for Science, Technology and Research 2NUS Graduate School for Integrative Sciences and Engineering 3Department of Biochemistry, Yong Loo Lin School of Medicine

The Wnt signalling pathway is commonly dysregulated in colorectal cancer, a disease in which PRL-3 (phosphatase of regenerating liver 3) has been implicated to play a key role in metastatic progression. In a search for potential PRL-3 regulated proteins in the Wnt pathway, beta-catenin was identified as a candidate regulated protein in A2780 ovarian carcinoma cells. In these cells, stable overexpression of PRL-3 (wild-type or catalytically dead) potently downregulated beta-catenin, whereas ablation of PRL-3 promoted beta-catenin accumulation. Significantly, this downregulation was found to be due to destabilization of beta- catenin protein, as proteosomal inhibition could effectively rescue the levels of this proteosomally-degraded protein. In a search for candidate dysregulated components of the beta-catenin degradation machinery, Dvl2/3 and Naked1/2 were identified to be antagonistically regulated by PRL-3: PRL-3 downregulated Dvl2/3, but upregulated Naked1/2. This is an intriguing result, given that Dvl has been reported to promote beta-catenin stability, whereas Naked sequesters Dvl to antagonize this protective effect on beta-catenin, thereby enhancing its degradation. The significance of beta-catenin downregulation to PRL-3-mediated oncogenesis is being actively studied.

32 POSTER 20

EGF signaling pathway involvement in regulating keratin dynamics in an Epidermolysis Bullosa Simplex disease model

Tong San Tan1,2, John E.A. Common1, Cedric Badowski1, E. Birgitte Lane1 1Institute of Medical Biology, Agency for Science Technology and Research 2NUS Graduate School for Integrative Sciences and Engineering

Epidermolysis Bullosa Simplex (EBS) is a human skin blistering disease caused by mutations in the keratin intermediate filament genes KRT5 or KRT14. Ker- atinocytes harboring the severe EBS Dowling-Meara mutation R125P on keratin 14 (Rod 1A domain) spontaneously form abnormal keratin aggregates, of which the nature of their formation are poorly understood. To investigate the molecular mechanism underlying the formation of mutant keratins in vivo, im- mortalized keratinocytes were stably transfected with EGFP tagged with either K14 wild-type or K14 R125P. Time-lapse imaging showed that EGFP-K14 R125P was localized as aggregates at the lamellipodial regions of the isogenic pathomimetic keratinocytes. Strik- ingly, these peripheral aggregates were highly dynamic, and were constantly undergoing assembly and disassembly upon cell migration. Protein extract analysis revealed an elevated level of phosphorylated ERK1/2 expression in mutant keratinocytes as compared to wild-type keratinocytes, and indirect immuofluorescence has shown that phosphorylated ERK1/2 co-localized with peripheral keratin aggregates of the mutant keratinocytes. MEK1/2 inhibitor was then used to inhibit ERK1/2 activity, which resulted in fewer mutant keratinocytes having aggregates. This observation was further supported by time-lapse live-cell imaging where ERK1/2 inactivation resulted in slower keratin dynamics at the leading edge, which could be ’rescued’ during wash- out. By targeting the upstream signaling pathway, removal of EGF resulted in a drastic reduction in the number of mutant keratinocytes having aggregates, which could be ’rescued’ by re-stimulation with EGF. In this study, we have identified that the EGF signaling pathway may be involved in regulating keratin dynamics in an EBS disease model.

33 POSTER 21

Cell Cycle Lipidomics

Jing Yan Lim1,2, Markus Wenk1,2 1Department of Biochemistry 2NUS Graduate School for Integrative Sciences and Engineering

Lipids play essential roles in many cellular processes, which functionally are linked to the cell cycle. Although many efforts have been put in to understand how lipids are regulated in the cell cycle, no high-resolution lipid profiling of the cell cycle has been reported. Using MCF-7 as a cell model, this study aims to provide novel insights into variation of a cellular lipidome during the cell cycle. Cells were synchronised using two pharmacological methods, collected at different cell cycle stages, and subjected to lipid analysis mainly by liquid chromatography- mass spectrometry (LC-MS). Out of 237 lipids measured quantitatively, specific molecular lipid species, including phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol and sphingomyelin, were shown to be regulated in both synchronisation methods. This preliminary study poses many interesting questions that are worth exploring in the future.

34 Poster Presentations: Chemistry

35 POSTER 22

Synthesis of Heterometallic Cobalt Clusters and Their Magnetic Properties

Pei Wang1,2, T.S. Andy Hor1,2 1NUS Graduate School for Integrative Sciences and Engineering 2Department of Chemistry

Transition metal clusters have been widely explored and shown prominent properties in molecular magnetism and metal catalysis.[1],[2],[3] We have synthesized a series of cobalt cubane clusters, which exemplify the importance of cobalt oxo- bridged cluster as building blocks for more complicated mono and heterometallic cluster. This has led to the incorporation of alkali metals, alkaline-earth metals and the rare-earth metals into the dicobalt cluster to yield intermetallic polynu- clear structures. The magnetic properties of these clusters are being explored. In this presentation, we shall outline the strategy and some resent ﬁndings in the cluster designs.

References [1] K. Isobe, Acc. Chem. Res., 1993, 26, 524-529. [2] Z. Weng, S. Teo, and T. S. A. Hor, Dalton Trans., 2007, 3493–3498. [3] Z. Weng, S. Teo, Z. P. Liu, and T. S. A. Hor, Organometallics, 2007, 26(12), 2950–2952.

36 POSTER 23

Mechanism of Hydrogen Peroxide Induced Keratinocyte Cell Sheet Migration

Loo Eng Kiat, Alvin1,2, Ho Rongjian2, Wong Yee Ting2, Barry Halliwell1,2 1NUS Graduate School for Integrative Sciences and Engineering 2Department of Biochemistry

Keratinocyte migration is an important process in wound healing. Numerous studies have shown that H2O2 can act as a signaling molecule for cell proliferation and migration. In this study, we focused on the eﬀect of H2O2 on keratinocyte cell sheet migration. We found that H2O2 induces a dose dependent increase in migration of HaCaT keratinocytes using a scratch wound assay. While both H2O2 and scratch wounding induce ERK 1/2 and p38 MAPK phosphorylation very strongly in keratinocytes, the phosphorylation induced by H2O2 was more long-lasting. Inhibition of either ERK 1/2 or p38 MAPK using pharmacological inhibitors reduced basal cell migration as well as inhibited H2O2 induced migration. Both scratch wounding and H2O2 were found to induce epidermal growth factor receptor (EGFR) phosphorylation. Inhibi- tion of EGFR phosphorylation also inhibited H2O2 induced migration as well as strongly reducing H2O2 induced ERK 1/2 phosphorylation but not p38 MAPK phosphorylation. This shows that H2O2 induced ERK 1/2 phosphorylation is largely due to the activation of EGFR phosphorylation. While the concentration of H2O2 used was non-cytotoxic and had a mild proliferative eﬀect, inhibition of EGFR, ERK 1/2 and p38 phosphorylation sensitizes the cells to H2O2. This implied that activation of these kinases not only induces cell migration but also ensures that the cell survives the insult.

37 POSTER 24

Targeting the “Turtle” – Metabolic Labelling of Inositol lipids

Shareef Mohideen Ismail1, Sandip Pasari2, Martin Lear2, Markus Wenk1,3 1NUS Graduate School for Integrative Sciences and Engineering 2Department of Chemistry 3Department of Biochemistry

The molecule inositol is extremely crucial to various cellular processes. Inos- itol lipids form components of cellular membranes and along with free inositols, participate in various signalling mechanisms. Higher inositol sphingolipids and glycosylphosphatidylinositol (GPI) anchors are known to be involved in host-pathogen interactions and in interactions of the cell with the extracellular environment. Absence of inositol biosynthesis and unavailability from the media causes auxotrophy in eukaryotes and some prokaryotes. Free and lipi- dated inositols have been studied through their organic synthesis with conju- gated fluorophores. Additionally, fluorescently-tagged inositol binding protein domains (PH, FYVE) have been used to locate inositol lipids within the cell. These methods, however, raise questions of specificity and differences from na- tive lipid behaviour. We attempt to develop a tool to specifically target inositol lipids utilizing metabolic labelling using inositol analogues modified with bioorthogonal groups. Budding yeast, Saccharomyces cerevisiae, was selected as the model organism to study the effects of the analogues on growth, their interactions with the cellular environment and analyze their incorporation into inositol lipids. Assessment of inositol analogue incorporation was performed through mass spectrometry of yeast lipid extracts. Here, we present some of our results which enhance our understanding of the effects of inositol analogues on the cellular environment.

38 Poster Presentations: Computer Science

39 POSTER 25

Designing Artiﬁcial Team-mates for Increased Aﬃliation

Tim Merrit1, Kevin McGee2 1NUS Graduate School for Integrative Sciences and Engineering 2Partner Technologies Research Group

An ongoing focus of HCI research has examined how humans treat computers socially, and in some ways similar to human-human interactions. This is of particular interest to interaction designers because it suggests factors that affect the way we play games or interact with technology. This research focuses on affiliation with team-mates in the context of real-time cooperative games, and examining how affiliation differs depending upon whether the team-mate is an avatar controlled by a computer or another human. Details of preliminary studies suggest that humans respond and affiliate with computer-based team-mates differently than with humans, yet there are promising results that suggest that design changes can be made to the computer-based team-mates to encourage an increase in affiliation.

40 POSTER 26

Rereadability in Procedural Hypertext Fiction

Alex Mitchell1 1NUS Graduate School for Integrative Sciences and Engineering

In hypertext fiction and other forms of interactive storytelling, rereadability and variability are seen as important differentiating factors between traditional and interactive stories. There has been extensive work investigating dynamic and adaptive non-fictional hypertext, procedural story generation and procedurally- driven interactive storytelling. There has also been much discussion of rereadability in literature, and replayability in computer games. However, there has not been any research into the specific techniques to support rereadability in computational, procedurally-driven interactive stories. My thesis research focuses on investigating the nature of rereadability in procedural hypertext fiction, and the ways in which a procedural approach to hypertext fiction can suggest new forms of rereadability. A deeper understanding of the techniques that can be used to support the reader’s experience of rereadability can help authors to create more compelling interactive stories, and encourage more absorbed, re- flective reading and rereading of interactive texts. To investigate this issue, the first step is to identify existing types of rereadability in interactive and non- interactive stories. Following this, different ways to support both existing and new forms of rereadability will be explored through rapid prototyping of authoring tools for procedurally-driven interactive hypertext fiction, and the creation of stories with these tools. The resulting stories will be tested with readers to investigate their response, and to gain further insight into how these techniques impact rereadability. This paper reports the initial findings of the research, and outlines the remaining challenges.

41 POSTER 27

State Space Reduction for Linearizability Checking

Zhang Shaojie1,2 1Department of Computer Science 2NUS Graduate School for Integrative Sciences and Engineering

The rapid development of hardware and network has brought distributed and pervasive computing systems to each corner of our society. They range from VLSI chips, to shared-memory multi-processors, local workstations, internet and etc. However, these systems, unlike traditional sequential centralized ones, are notoriously hard to understand and design correctly. Engineers have to consider a huge number of complicated interactions and interferences among different users. Meanwhile, our society depends increasingly heavily on computer systems, making guaranteeing their correctness imperative. One successful approach is model checking, which is a fully automatic formal technique to prove/dis-prove properties of finite state systems. It has established itself as an effective verification technique in the last two decades. However, as the number of system components increases linearly, the state space generated by a system can blow up exponentially beyond the limit of machine memory. Therefore, in this paper I first present a method that utilizes model checking technique to verify linearizability, a popular correctness criterion for concurrent data structures. Then I investigate the problem of state space reduction for this method, and improve the verification algorithm by combining partial order reduction and symmetry reduction techniques. Finally I demonstrate the efficiency of the combined method on several well-known concurrent data structures.

42 POSTER 28

Non-negative Matrix Factorization with KL Divergence Criterion Equals Maximum Likelihood Decomposition

Wang Xuancong1,2, Sim Khe Chai1 1School of Computing 2NUS Graduate School for Integrative Sciences and Engineering

Non-negative matrix factorization (NMF) is a very useful tool for learning non- negative basis for statistical data analysis. It is able to learn the Mel-frequency- scale (the frequency resolution of human’s cochlear) ﬁlter-banks for feature extraction for speech recognition [1]. In this work, we have shown that NMF using KL divergence criterion is mathematically equivalent to maximum likelihood under several normalization constraints by treating each non-negative observation feature vector (each column of Y in Y=A*X) as a weighted (by each column of X) mixture distribution of several random processes (each one with its own distribution described by columns of the basis matrix A) rather than a Euclidean vector. And thus Gaussian Mixture Model is a special case of NMF by constraining the basis vectors to be Gaussian. We have also done some experiments showing that NMF is able to capture inherent correlation but is biased by the mean energy in each elements of the observation feature vector. Also the current NMF iterative procedure has the same problem of converging to local optimum as the Expectation Maximization iterative process. Nonethe- less, by using random initialization, NMF is able to capture an approximately optimal set of basis vectors which can minimize the reconstruction error (measured in terms of KL divergence) of the original data which might be useful for non-negative-type data compression.

[1] Alexander Bertrand, Kris Demuynck, Veronique Stouten, Hugo Van hamme, UNSUPERVISED LEARNING OF AUDITORY FILTER BANKS USING NON- NEGATIVE MATRIX FACTORISATION, IEEE 2008

43 POSTER 29

Domain Adaptation for Semantic Role Labeling in the Biomedical Domain

Daniel Dahlmeier1, Hwee Tou Ng1,2 1NUS Graduate School for Integrative Sciences and Engineering 2Department of Computer Science, School of Computing

Semantic role labeling (SRL) is the natural language processing task of automatically identifying those parts of a sentence that contain the answers to simple questions of the form “-Who did what to whom when and where?”-. SRL is a first step towards enabling computers to understand the meaning of human language. Thus, it has the potential to greatly benefit information extraction and data mining from free text. The problem with SRL is that it requires a large number of manually annotated examples to learn accurate statistical models. While these resources exist for the newswire domain, there are only few such resources for the biomedical domain. Creating these resources is an expensive and laborious task. It is desir- able to leverage existing SRL resources as much as possible to reduce the need for new annotated examples. In our work, we address SRL for the biomedical domain as a domain adaptation problem. That is, we want to adapt a statistical SRL model learned from newswire texts (the source domain) to biomedical texts (the target domain). We evaluate the performance of three recently proposed domain adaptation algorithms for SRL. We are the first to investigate the extent of manual annotation needed to port an SRL system trained on newswire text to biomedical text by explicitly determining the number of annotated biomedical text examples needed to achieve good performance. Our results show that by using domain adaptation the cost for developing an SRL system for the biomedical domain can be reduced significantly.

44 POSTER 30

SOPRAN: Scalable Online Proactive Re-optimization in Virtual Machine Management with Dynamic Workloads

Jian Zhou1, Lei Shi2, Kian-Lee Tan1,2 1NUS Graduate School for Integrative Sciences and Engineering 2School of Computing

For a data center to operate effectively (i.e., meeting customers’ Service Level Agreements (SLAs)) and efficiently (i.e., minimizing resource consumption), the virtual machines (VMs) must be carefully managed. In particular, as workloads change, the resource demands of VMs change, which in turn may render the assignment of VMs to physical machines sub-optimal. In this paper we propose SOPRAN, a Scalable Online Proactive Re-optimizAtioN algorithm, that can dynamically adapt the assignment of VMs to physical machines to keep the resource utilization low without sacrificing the SLAs. SOPRAN characterizes the dynamic workloads in the system using a risk cube model, and approximates the workload demands with a representative state set. The optimal plan for each representative state is incrementally generated, forming the switchable plan set. At runtime, a two-phase re-optimization strategy matches the current system demand to the closest representative state and actuates the corresponding plan in the switchable plan set. At the same time, online monitors profile the actual demands and refine the risk cube to guarantee the model’s accuracy. We evaluated SOPRAN against the state-of-the-art IBM MFR algorithm. The results show that, with comparable resource consumptions, SOPRAN can achieve more stable SLA violation rate of no more than 4%, 80% lower migration rate, and save up to 90% re-optimization overhead.

Poster Presentations: Engineering

47 POSTER 31

Mesoporous Poly-Melamine-Formaldehyde for Reversible Carbon Dioxide Adsorption

Mei Xuan Tan1,2, Yugen Zhang1, Jackie Y. Ying1,2 1Institute of Bioengineering and Nanotechnology 2NUS Graduate School for Integrative Sciences and Engineering

Mesoporous poly-melamine-formaldehyde (PMF) has been developed and synthesized through a simple one-step reaction using melamine and paraformalde- hyde, both of which are inexpensive and common industrial chemicals. The resulting organic polymer is highly porous with surface areas up to 1100 m2/g, pore width ranging from 6 nm to 23 nm and total pore volume and micropore volume of up to 3.46 cm3/g and 0.21 cm3/g respectively. It is the ﬁrst time that highly mesoporous melamine-formaldehyde polymer has been synthesized without the use of inorganic templates or porogens. PMF is found to have high eﬃciency in reversible CO2 adsorption. The CO2 adsorption is instantaneous, reversible and recyclable. The highest CO2 adsorption capacity obtained for PMF is 18.7 wt%. This high capacity of PMF for CO2 adsorption exceeds that of the organic polymers previously reported in the literature, and is comparable to some zeolites and metal-organic frameworks (MOFs) that have been investigated for CO2 adsorption. The CO2 adsorption capacity of PMF is correlated with its micropore volume. Due to its robust porosity, high surface area and high percentage of amine groups, PMF has many potential applications in gas adsorption, gas capture and catalysis, and as a functional material.

48 POSTER 32

Surface-Functionalized and Surface-Functionalizable Poly(vinylidene ﬂuoride) Graft Copolymer Membranes via Click Chemistry and Atom Transfer Radical Polymerization

Cai Tao1, Kang En-tang1 1Department of Chemical and Biomolecular Engineering

Poly(vinylidene ﬂuoride) (PVDF) with azide-functionalized poly(glycidyl methacrylate) (PGMA) side chains (PVDF-g-P[GMA-(N3)(OH)]) were synthesized via free radical-initiated graft copolymerization of glycidyl methacrylate (GMA) from ozone-pretreated PVDF backbone (PVDF-g-PGMA), followed by reaction of the oxirane rings in the GMA side chains with sodium azide. Alkyne- functionalized poly(N-isopropylacrylamide) (alkynyl-PNIPAM), prepared a priori by atom transfer radical polymerization (ATRP), was used for the click reaction with the azido-containing PGMA side chains of the PVDF-g-P[GMA- (N3)(OH)] copolymer to give rise to the thermoresponsive PVDF-g-P[GMA- click-PNIPAM] copolymer. Both the PVDF-g-P[GMA-(N3)(OH)] and PVDF-g- P[GMA-click-PNIPAM] copolymers can be readily cast into microporous membranes by phase inversion in an aqueous medium. The PVDF-g-P[GMA-(N3)(OH)] microporous membranes with azido-containing surfaces could be further functionalized via surface click reaction with alkyne-terminated PNIPAM to obtain the PVDF-g-P[GMA-click-PNIPAM]surface microporous membranes. The surface composition and morphology of the PVDF-g-P[GMA-click-PNIPAM] membranes can be adjusted by the temperature of casting medium, while the ﬂux through both types of membranes exhibits thermoresponsive behavior.

49 POSTER 33

Electrospun Nanoﬁbrous Composite for Osteogenic Diﬀerentiation of Mesenchymal Stem Cells

Luong T. H. Nguyen1, Susan Liao2, Seeram Ramakrishna3, Casey K Chan4 1NUS Graduate School for Integrative Sciences and Engineering 2School of Materials Science and Engineering, Nanyang Technological University 3Department of Mechanical Engineering 4Orthopedic Surgery, National University Health System

In the body, almost all tissue cells reside in a three-dimensional (3D) environment where cell-cell interactions as well as the presentation of chemical, physical and mechanical cues in the surrounding fluid and extracellular matrix (ECM) provide the guidance for cellular responses. In nature bone, type I collagen is a major protein in organic matrix, approximately 95%. Collagen fibrils had a diameter range in nanometer scale and orderly deposited by nano-hydroxyapatite (n-HA) mineral crystals. Mimicking these hierarchical structures is a gold strategy for the design and fabrication of bone graft materials. We have hypothesized that electrospun nanofibrous composites mimicking natural ECM enriched with mesenchymal stem cells (MSCs) will promote bone regeneration. The studies on typical two-dimensional (2D) nanofibrous scaffolds were performed to determine cellular responses to electrospun nanofibres for the osteogenic differentiation of human MSCs (hMSCs). Additionally, biomimetic nanocomposites of poly(L-lactic acid)/Collagen (PLLA+Col) nanofibres deposited with n-HA were designed, and the results indicated that sustainable supply of Ca/P ions locally effectively induced the osteogenic differentiation of hMSCs at very early time point, even without any osteogenic supplement. Preliminary studies of using 3D nanofibrous scaffolds in cell culture were also performed. There was a significant difference in cell behaviors of hMSCs in the osteogenic differentiation process when they were cultured in 3D- and on 2D- electrospun PLLA nanofibrous scaffolds. The 3D scaffolds considerably enhanced the osteogenic ability of hMSCs comparing to the 2D scaffolds. As such, biomimetic nanofibrous scaffolds were shown as a gold strategy for directing osteogenic differentiation of hMSCs.

50 POSTER 34 Biological Adhesives as Initiator Anchors for Surface-initiated Polymerization in the Preparation of Multifunctional “Green” Surfaces

Wenjing Yang1, Gary H. Dickinson2, Serena Lay-Ming Teo2, Tao Cai1, Koon-Gee Neoh1, En-Tang Kang1 1Department of Chemical and Biomolecular Engineering 2Tropical Marine Science Institute

Tethering of functional polymer brushes on the surface is an effective strategy to impart antifouling and antibacterial properties to the materials, and is of crucial importance to the effective performance and long service life of biomaterials.[1] In the surface-initiated (SI) polymerization method to prepare well-defined polymer brushes, the presence of a stable and durable layer of initiators on the surfaces is indispensable.[2] Compared to chemical coupling agents that have been widely used to immobilize the initiators on various substrates,[3] biomimetic anchors inspired by biological adhesives are environmentally-friendly, stable and adherent to a variety of substrates.[4] In the present work, barnacle adhesive, a common biological adhesive from marine organism barnacles (Amphibalanus amphitrite), was used as the initiator anchor for SI polymerization to impart multifunctional properties to stainless steel surfaces. Thus, the amine moieties of the barnacle adhesive were allowed to react with 2-bromoisobutyryl bromide to provide the alkyl halide initiator for the surface-initiated atom radical transfer polymerization of 2-hydroxyethyl methacrylate (HEMA). The hydroxyl groups of HEMA polymer brushes were then converted into carboxyl groups for coupling of chitosan to impart the stainless steel surface with both antifouling and antibacterial properties. The surface-functionalized stainless steel was very effective in preventing protein adsorption and reducing bacterial adhesion, and exhibited antibacterial efficacy against Escherichia coli. Key word: Barnacle adhesive, surface-initiated atom transfer radical polymerization, antifouling, antibacterial

Reference [1] Xu, F. J.; Neoh, K. G.; Kang, E. T. Bioactive surfaces and biomaterials via atom transfer radical polymerization. Prog. Polym. Sci. 2009, 34, 719-761. [2] Edmondson, S.; Osborne, V. L.; Huck, W. T. S. Polymer brushes via surface initiated polymerizations. Chem. Soc. Rev. 2004, 33, 14-22. [3] Ma, H.; Wells, M.; Beebe, T. P.; Chilkoti, A. Surface-initiated atom transfer radical polymerization of oligo(ethylene glycol) methyl methacrylate from a mixed self-assembled monolayer on gold. Adv. Funct. Mater. 2006, 16, 640- 648. [4] Smith, A. M.; Callow, J. A. Biological Adhesives. Springer-Verlag, Berlin, 2006.

51 POSTER 35

Nonlinear Control of Underactuated Systems With Applications to Autonomous Robotics

Guo Zhaoqin1 1Department of Electrical and Computer Engineering

In this work, we deal with one of the most challenging control problems - controlling a class of nonlinear underactuated systems with uncertainties. An underactuated unicycle system is used throughout the work to illustrate the effectiveness of the proposed controllers. Firstly, a synthesized integral sliding mode controller (ISMC) is proposed, which offers a practical solution. The ISMC, constructed with a suitably cho- sen integral sliding surface, is able to completely nullify the influence from any matched factors, especially the matched uncertainties. As a consequence, a sliding manifold is generated, in which the controller design can focus on the unmatched factors only. A unique advantage of the ISMC is its preservation of the same number of actuators in the sliding manifold as the original system. From practice, a linear state-feedback controller, simple and smooth, is found adequate in stabilizing the sliding manifold in a wide range around the equilib- rium. However, it is extremely difficult to verify the effectiveness of such a linear state feedback for underactuated systems in the presence of unmatched factors such as unmatched uncertainties. A main contribution of this part of work is to explore the design issue and effectiveness of the linear controller for the underactuated systems. First we reformulate the unmatched factors into several representative forms, then the linear matrix inequality approach is employed to design the feedback gains and maximize the stability region concurrently. Next, a gain-scheduling fuzzy logic controller (FLC) for the unicycle system, which is a partial model based design, is presented in this work. The FLC structure design is model-free and quite user-friendly. However, we encounter the difficulty in tuning FLC parameters. A linear LQR controller is effective in a local region of the origin, thus a local linearized system model based parameter tuning method which incorporates LQR linear feedback is proposed. Through comprehensive simulation-based investigations, the effectiveness of the proposed FLC is validated, and FLC shows superior performance than the LQR. The design procedure indicates that we can easily extend a linear controller to a nonlinear one like FLC to achieve more robust performance with respect to task and plant parameter variations. We can further improve the control performance through fine tuning FLC parameters or choosing more generic FLC structure components such as choosing different rule numbers, membership functions, fuzzy inference methods, or choosing different consequent part. Our future work will focus on totally model free and intelligent controller design.

52 POSTER 36

Analysis and Control of Closed Quantum Systems Based on Real-valued Dynamics

Xue Zhengui1, Lin Hai2, Lee Tong Heng1,2 1NUS Graduate School for Integrative Sciences and Engineering 2Department of Electrical and Computer Engineering

Quantum control is concerned with active manipulation of physical and chemical processes on the atomic and molecular scale. Quantum control has attracted great attention of researchers because of the unique properties of quantum systems, such as the coherent superposition. Among various applications of quantum phenomena, quantum computation is a hot topic due to its really exciting features, e.g., the parallelism computation. To make full use of quantum phenomena, it is of great significance to actively manipulate quantum systems. Our work aims to facilitate quantum control design by making use of a derived real-valued dynamics, which is equivalent to the Schrödingerequation. Firstly, to obtain the real-valued dynamics, a pure state identication approach is presented. Secondly, the real-valued dynamics is deduced for both two- and three-level systems. The procedure is also extended to n-level systems. Thirdly, the real-valued dynamics can facilitate the analysis and design of quantum control. It assists one to make full use of classical control theory to implement quantum control. Among various control approaches, a control strategy based on Lyapunov analysis is considered. Proceeding from the existing Lyapunov control based on the Schrödingerequation, the state transfer problem is studied with the assistance of the real-valued dynamics. With the designed control, the goal state is not necessarily to be an eigenstate of the internal Hamiltonian, and the state transfer convergence can be achieved without any constraints on the internal Hamiltonian.

53 POSTER 37

A Real-time Reconstruction Approach for AR-based Applications

Jiang Shuai1,2, Ong Soh Khim1,2, Andrew Y. C. Nee1,2 1Department of Mechanical Engineering 2NUS Graduate School for Integrative Sciences and Engineering

Due to the recent development in real-time camera tracking, an increasing amount of research eﬀort has been devoted to vision-based real-time reconstruction, which is also known as the vision-based tracking-and-reconstructing technique. With the capability to produce high frame rate virtual models, real- time scene reconstruction has become an integral part for many AR (augmented reality) based applications. However, as many reported approaches have been focused primarily on the accurate modeling of the entire scene, the lack of mechanism to obtain information on the components of the real scene, e.g., the physical distribution of the objects in the scene, may have restricted the range of applications. In this study, a new reconstruction approach is proposed. It adopts a point analysis mechanism to identify possible point clusters in the map. As each identiﬁed point cluster can be regarded as the virtual representation of a corresponding object in the real scene, information on the location and the shape of the real objects in the scene can be retrieved in real-time. By employing this approach, after the real objects have been reconstructed based on the clustering results, the retrieved shape and location information could be used to support advanced operations in many AR-based applications. The potential of this approach is demonstrated through some experiments.

54 POSTER 38

Image Correlation Spectroscopy as a Tool for Microrheology of Soft Materials

Nicholas Agung Kurniawan1, Chwee Teck Lim1,2,3, Raj Rajagopalan1,4,5 1NUS Graduate School for Integrative Sciences and Engineering 2Department of Mechanical Engineering 3Department of Bioengineering 4Department of Chemical and Biomolecular Engineering 5Chemical and Pharmaceutical Engineering Program, Singapore-MIT Alliance

Image correlation spectroscopy (ICS) is a family of biophysical methods that has been used to perform spatiotemporal measurements on biological materials, especially cells. Some of the early uses of ICS include quantifying spatial distribution, aggregation state, diffusion coefficient, as well as flow and interaction of cellular protein molecules. In the present work, we show, in addition to these original applications, how ICS can be used to perform microrheological measurements (µR) of complex, viscoelastic materials. We test the method, which we call ICS-µR, on Newtonian fluids as well as complex, viscoelastic fluids with different viscosities and viscoelastic behaviors. Comparison of ICS-µR results with reported data from the literature as well as results from conven- tional rheological measurements yields excellent agreement. Furthermore, we develop a special technique for extracting mean-squared displacements of tracer particles in the samples from image correlation data; the technique successfully reproduces previously published experimental data on a wide range of soft materials displaying a broad range of scaling behaviors. This technique can be applied to improve the accuracy of other microrheological measurements and can potentially offer new insights on the power-law behaviors of materials. The possibility to combine spatiotemporal assessment and time- and length-scale dependent microrheological measurements from images of fluorescent molecules makes ICS-µR a prospective tool in many biophysical applications.

55 POSTER 39

Metabolic Networks Based Approach for Understanding Structural Organization Principles of Essential Genes

Ma Jing1,2 1Centre for Computational Science and Engineering 2NUS Graduate School for Integrative Sciences and Engineering

Misuse of antibiotics had raised the concern of antimicrobial resistant for decades, thus characterizing sensitive targets in these “superbugs” is an urgent challenge. Essential genes are vital for growth/viable making them ideal candidate targets of study. Identifying essential genes via genome-scale knockout experiments are resource intensive and are not universally applicable for all species. Here we propose a metabolic network based approach which aims to understand the structural organization principles of essential and non-essential genes from Es- cherichia coli. Each gene has a corresponding ’damage list’ where the overall reactions can be aﬀected by gene knockout. Our analysis indicates that essential genes tend to aﬀect reactions catalyzed by other essential genes. This is also the case for non-essential genes. Besides, two genes with highly correlated damage lists tend to similarly linked to their respective essentiality, i.e. both are essential or non-essential. Our results suggest a complementary strategy to knockout experiments to identify essential genes in a genome.

56 POSTER 40

Toxicant-induced Sexual Dimorphic Responses in Zebra Fish Metabolic System

Zhang Xun1,2 1Centre for Computational Science and Engineering 2NUS Graduate School for Integrative Sciences and Engineering

Environmental contaminants constitute an unavoidable menace to human health. Understanding the mechanisms of toxicity cause by these contaminants especially at the in vivo system is a demanding task. Also, sex-dependent toxicity is also an important issue to address. In this study, we used zebra fish as an aquatic vertebrate model to assess toxicant-induced hepatotoxicity. By integrating topological analysis of metabolic network and transcriptome profile, we observed differential sexual dimorphic toxic responses when fishes were ex- posed to toxicants such as mercury, 4-nitrophenol, and 4-chloroaniline for up to 4 days. This suggests differential metabolic activities of male and female fish to undergo homeostasis to these toxicants. Intriguingly, the sexual dimorphic effect makes a more important role in determining gene expression profile even comparing with the impact of toxicants difference. Using gene enrichment analysis, we found lipid metabolism pathway and several relevant pathways behave oppositely among male and female fish under toxic exposure. Overall, our study emphasizes the significance of sexual dimorphism of metabolic system in toxic responses. This work can shed light in future endeavors to decipher sex-dependent alteration of metabolism leading to toxicity and pathology.

57 POSTER 41

Remote Maintenance using Augmented Reality Technology

Zhu Jiang1,2, Andrew Yeh-Ching Nee1,2, Patricia Soh-Khim Ong1,2 1Department of Mechnical Engineering 2NUS Graduate School for Integrative Sciences and Engineering

Remote maintenance enables disparately located workers to collaborate with one another on maintenance tasks, and Augmented Reality (AR) technology can provide a useful interface between virtual and real worlds to facilitate these tasks. In this interdisciplinary research, an AR-assisted remote maintenance system will be designed and developed. Such a system will enable the on-site worker to retrieve related information (e.g., maintenance procedures) that can be augmented virtually with the real equipment, collaborate with the remote operator via intuitive multimedia files (e.g., videos and 3D models) in addition to verbal communication, and interact with the system and databases via an integral user interface. This research aims to explore the benefits of applying AR technology in maintenance operations and design the necessary interfaces needed. Related key research issues include tracking and registration, collaborative system design, human-system interaction, information filtering, maintenance data management, etc. Thus far, an online authoring tool, Online Author- ing for Augmented Reality Remote Maintenance (OAR2M), has been partially designed and developed. OAR2M enables the user to create 3D augmentations (e.g., animating virtual replicas of real objects) without a-priori knowledge of the environment, and such augmentations enable more intuitive and efficient collaboration between disparately located operators.

58 POSTER 42

Augmented Reality 3D Design Space

Ng Lai Xing1 1Mechanical Engineering, AR Lab

Augmented reality (AR) is a novel technology that synthesizes real and virtual objects to create an AR environment where the users can interact with both types of objects. In this research, an AR 3D design space will be developed together with complementary design theories and methodologies. By applying AR technology in a design space, an interactive conceptual design environment can be created to provide intuitive interaction tools for concept modeling, multi- modal visualization and contextualization of augmented prototypes and comprehensive product information during conceptual design. Such a design space will be simple enough for the layman to carry out design tasks. Thus, the customers will be able to participate in the conceptual design stages as designers and end-users at the same time. A niche area of toy design by the customers (i.e., children) has been identified as an application area of this research and the aim of the research is to create an AR 3D design space that is suitable for use by children. Key technological areas covered in the research include 3D tracking, 3D reconstruction and modeling, interaction techniques in AR and multi-modal product visualization. In the past two years, these areas have been analyzed and integrated to design and develop two applications, namely AR Computer-Aided Design Environment (ARCADE) and Gesture-based AR Design Environment (GARDE), which demonstrate the use of AR in design. By matching the benefits of using AR with the requirements of conceptual design, this research aims to advance the knowledge in both fields and create new ways of conceptual design.

59 POSTER 43

Electrophysiological consequence of genetic perturbation in gastrointestinal diseases — a computational investigation

Poh Yong Cheng1,2, Martin Buist1,2 1Division of Bioengineering 2NUS Graduate School for Integrative Sciences and Engineering

The gastrointestinal tract is critical to the body for the acquisition of nutrients, water and even drugs. Gastrointestinal dysmotility afflicts a significant portion of the population. Sustained sufferance of such disorders lowers quality of life (e.g. pain, poor nutrition) and incurs direct and indirect economic and social costs. The poor understanding of mechanisms underlying gastrointestinal disorders hampers effective treatment and patient management. Computational techniques are an increasingly popular approach that contributes to uncovering etiology and complements traditional biological experimental methods. Of particular importance is the capability of computational methods to integrate vast amount of experimental data, across spatial and temporal scales, to understand how components of a system interplay to engender physiology or patho- physiology. In the context of the gastrointestinal tract, recent epidemiological studies and genetic studies have suggested that mutations of the sodium channel protein complex could potentially contribute to functional gastrointestinal disorders. Heterologous expression systems in HEK cells found these mutations altered sodium channel electrophysiology, which raised further questions as to how the same mutations could adversely affect gastrointestinal cells. A computational framework was used in an initial attempt to evaluate the electrophysiological consequence of these mutations. Mutation altered sodium channel electrophysiology was modeled and verified. Subsequently, the sodium channel model was integrated into gastrointestinal cell models and in silico experiments were performed to evaluate the impact of these mutations. Electrics affects me- chanics and therefore a genetic perturbation may lead to disrupted electrics and dysmotility at the global scale.

60 POSTER 44

Magnetism and Magnetotransport Studies in Ge0.9Mn0.1Te

Lim Sze Ter1,2, J. F. Bi2, K. L. Teo2, and T. Liew2,3 1NUS Graduate School for Integrative Sciences and Engineering 2Department of Electrical and Computer Engineering 3Data Storage Institute

Ferromagnetic semiconductors have received much attention because of the nov- elty of their fundamental properties and also due to their potential as the basis of future semiconductor spintronic technologies which promise integration of magnetic, semiconducting and optical properties and a combination of information processing and storage functionalities. However, it has been a challenge to grow homogeneous ferromagnetic semiconductors epilayers and with high Curie temperature (Tc). The formation clusters is often observed in semiconductors doped with transition metals. These condensed magnetic semiconductors or clusters can be in the form of observable secondary phases or regions of subtle spinodal decomposition. The high quality of these epilayers is highly dependent on the growth conditions. In IV-VI ferromagnetic semiconductor such as Ge1−xMnxTe, two different growth conditions with the same Mn concentration of 8% can lead to different magnetic properties and Curie temperatures. The temperature dependence of magnetization (M-T) had showed one with concave and other with convex behavior, which was suggested to have a short range and long range ferromagnetism, respectively. We have investigated the magnetic and magnetotransport properties of Ge1−xMnxTe (x = 0.1) grown by molecular-beam epitaxy. Our results show that the sample exhibits two ferromagnetic transition temperature at Tc = 34 K and Tc * = 100 K. We infer that Tc is a long range ferromagnetic ordering in view of sufficient carriers generating uniform ferromagnetism while Tc * is a short range ferromagnetic ordering due to ferromagnetic clusters. The temperature dependence of the resistivity (ρ-T) curve exhibits a shallow minimum near Tc. The upturn of ρ-T the low temperature (T < Tc) is well described by a weak-localization model while in the high temperature regime (T > Tc), the phonon scattering dominates.

61 POSTER 45

Multi DOF Active Vibration Isolation and its Application in Precision Pointing of Flexible Spacecrafts

Liu Lei1, K K Tan2, S Huang, T H Lee 1NUS Graduate School for Integrative Sciences and Engineering 2Department of Electrical and Computer Engineering

Passive vibration isolation is inadequate for precision engineering applications with strict requirements, especially in handing random and low frequency dis- turbances. There is also trade-oﬀ problem between base vibration isolation and payload disturbance rejection. However, active vibration isolation can overcome these shortcomings. In this paper, multi degree-of-freedom (DOF) active vibration isolation and its application in spacecrafts is presented. Model reference adaptive control(MRAC) with acceleration feedback is used to isolate random disturbance. PID control is augmented with displacement feedback to suppress vibration displacement. The MRAC-PID composite control is applied to a 4- leg platform to isolate vibrations and suppress tip/tilt jitters. The scheme is used to isolate 6 DOF vibration and steer the payload on a ﬂexible spacecraft. Satisfactory performance of vibration isolation and jitter removing is achieved.

62 POSTER 46

Morphological Tuning, Self-assembly and Optical Properties of Indium Oxide Nanocrystals

Zhang Shuangyuan1, Ye Enyi2, Han Mingyong2,3 1NUS Graduate School for Integrative Sciences and Engineering 2Institute of Materials Research and Engineering, Agency for Science Technology and Research 3Division of Bioengineering

In our research, weak acids, weak bases or their mixtures were used as reaction media/coordinating ligands to achieve a systematic morphological control of amphoteric indium oxide nanostructures. Diﬀerent indium/oleic acid molar ra- tios from 1:0, 1:1, 1:2, 1:3, 1:6 and 1:15 in non-coordinating, weak-coordinating, strong-coordinating and their mixed media were adopted to prepare irregular aggregated nanoparticles and uniform regular/truncated octahedrons, etc. In addition to their strong size-dependent absorption, single-crystalline indium oxide octahedrons also gave a strong band-edge emission while irregular indium oxide aggregated nanoparticles only exhibited a weak deep-trap emission. Mean- while, the truncated octahedrons were self-assembled into either zigzag lines or pentagram patterns, and the regular octahedrons and truncated cubes were self-assembled into hexagonally packed nanocrystal arrays. In addition, the formation mechanism of the various nanostructures under diﬀerent conditions was investigated in details.

63 POSTER 47

Genome-scale Modeling and in silico Analysis of Pichia pastoris for Biotechnological Applications

Chung Kai Sheng, Bevan1, Lee Dong-Yup1 1Department of Chemical & Biomolecular Engineering

The methylotrophic yeast Pichia pastoris has been recognized as a useful expression system for recombinant glycoprotein production. As glycoproteins are key products in the biopharmaceutical industry, there is great interest in developing an efficient technology for manufacturing these biomolecules. Experimental protocols have been established over the past decades to study and engineer P. pastoris in the aspects of protein biosynthesis, glycosylation and secretion. However, few have focused on the organism’s metabolism, which is a fundamen- tally characteristic of cellular physiology. Hence, we have developed an in silico metabolic model, based on the genome of P. pastoris, to serve as a platform for rational design and analysis of the organism for various biotechnological applications. Following a systematic procedure, we reconstructed a genome-scale metabolic model which accounts for 668 genes, 1,177 metabolites and 1,361 reactions that are appropriately segregated into eight subcellular compartments. Computational simulations of cellular phenotype, using constraints-based flux analysis, agree well with our experimental observation carried out in a chemo- stat and other existing literatures. Metabolite-centric analysis allowed us to gain insight into the metabolism of P. pastoris and propose potential strategies to enhance its metabolic capabilities for recombinant protein production and also biotransformation, which is the use of the microorganism to perform chemical modification. In conclusion, the novel genome-scale metabolic model of P. pastoris is a useful tool for studying cellular metabolism and developing rational metabolic engineering strategies for strain improvement. Due to the complexity of the metabolic network, the computational approach allows us to identify non-intuitive targets for genetic manipulation and gain valuable insights into the sophisticated metabolic functions of the organism.

64 POSTER 48

Quantitative Analysis of Surface Pluripotent Marker Expression on Human Embryonic Stem Cells (hESCs) during Diﬀerentiation Using hESC - Speciﬁc Antibodies

Lesley Y Chan1,2,3, Evelyn KF Yim2,4,5, Andre B Choo1,2,3 1NUS Graduate School for Integrative Sciences and Engineering 2Bioprocessing Technology Institute 3Division of Bioengineering 4Department of Surgery 5RCE Mechanobiology

Human embryonic stem cells (hESCs) have great potential for regenerative medicine, but accurate identification and isolation of cell populations are first required. Currently, there are five accepted markers for undifferentiated hESCs; unfortunately, these markers also identify embryonal carcinomas and/or mouse ESCs. Therefore, our group generated a panel of monoclonal antibodies which are specific to undifferentiated hESCs. However, the sensitivities of the antibodies to the undifferentiated hESC state have not been quantified. The sensitivity of hESC markers has usually been evaluated by the percentage of positively fluorescing cells; but, a protein expression threshold level may be the determining factor of the cell state. Thus, it may be more accurate to quantify the protein expression level rather than the percentage of fluorescing cells when evaluating hESC and define sensitivity as the rate at which the marker expression changes with differentiation. This study aims to quantitatively analyze the sensitivity of the new panel of antibodies by evaluating the median fluorescence of surface antigen expression as the hESCs undergo spontaneous, hepatic, chondrogenic, and neural differentiation. We profiled the expression of six antibodies — mAb 5, mAb 84, mAb 85, mAb 529, anti-SSEA1, and anti-Tra-1-60 — using flow cytometry at 3-6 day intervals. As hESC differentiation progressed, mAb 84, mAb 85, mAb 529 and anti-Tra-1-60 marked decreases in antigen expression. In contrast, mAb 5 and anti-SSEA1 marked antigens with increasing expression during differentiation. The sensitivity analysis indicated that mAb 84 and anti- Tra-1-60 are the strongest negative indicators for differentiation, while mAb 5 and anti-SSEA1 are strong positive indicators. We envisage that through these analyses, we will be able to identify and separate sub-populations of hESCs during differentiation; and more importantly, determine at which stage hESC tumorigenicity is eliminated.

65 POSTER 49

Hybrid Control for Unmanned Helicopters

Ali Karimoddini1, Lin Hai2, Ben Chen2, T. H. Lee2 1NUS Graduate School for Integrative Sciences and Engineering 2Department of Electrical and Computer Engineering

The embedded controller in the avionic system of an Unmanned Aerial Vehicle (UAV) has a sophisticated structure that makes the UAV able to accomplish complicated missions, autonomously. In this structure, an essential issue is com- prehensively capturing the interactions between their continuous and discrete dynamics within a uniﬁed framework. Moving towards this ambitious goal, we have proposed a hierarchical hybrid controller for a UAV helicopter. In this hierarchy, the regulation layer of a UAV helicopter will be discussed with more details. The regulation layer is a control layer that is directly connected to the avionic system of the UAV and can manipulate the actuators and read the sensor information. It also could be governed by a supervisor to select a proper control mode and to follow a certain trajectory. The proposed model of the regulation layer consists of two control modes: the velocity-control and the position-control for which separate controllers have been designed. The resulting model is a hybrid system with linear dynamics and nonlinear jumps. We have analyzed the stability of the overall hybrid system under slow switching. The proposed hybrid model depicts the interrelations between the control modes of operation, the discrete transitions, the jumps in the continuous part of model, and the discrete and continuous dynamics of the system and the designed controller can ﬂexibly command the UAV to perform desired missions.

66 POSTER 50

Soft Tissue Discrimination in Magnetic Resonance Elastography Using a New Elastic Level Set Model

Li Bing Nan1, Chui Chee Kong2, Ong Sim Heng3,4, Numano Tomokazu5, Washio Toshikatsu6, Kobayashi Etsuko6 1NUS Graduate School for Integrative Sciences and Engineering 2Department of Mechanical Engineering 3Department of Electrical and Computer Engineering 4Division of Bioengineering 5Radiology, Tokyo Metropolitan University, Japan 5Biomedical Imaging, National Institute of Advanced Industrial Science & Technology, Japan 6Biomedical Precision Engineering, University of Tokyo

Magnetic resonance elastography (MRE) noninvasively images the propagation of mechanical waves within soft tissues. The elastic properties of soft tissues can then be quantified from MRE wave snapshots. Various algorithms have been proposed to obtain their inversion for soft tissue elasticity. Anomalies are as- sumed to be discernible in the elasticity map. We propose a new elastic level set model to directly detect and track abnormal soft tissues in MRE wave images. It is derived from the Mumford-Shah functional, and employs partial differential equations for function modeling and smoothing. This level set model can in- terpret MRE wave images without elasticity reconstruction. The experimental results on synthetic and real MRE wave images confirm its effectiveness for soft tissue discrimination.

67 POSTER 51

Design and Engineering of Cellulose Ester Membranes for Forward Osmosis

Zhang Sui1, Wang Kai Yu1, Chung Tai-Shung1, Y. C. Jean2, Chen Hongmin2 1Department of Chemical and Biomolecular Engineering 2Department of Chemistry, University of Missouri-Kansas City

Worldwide attention has been paid to forward osmosis (FO) in recent years as a prospective desalination technology for the production of fresh water. With osmotic pressure as the driving force, FO possesses unique advantages of low energy consumption, anti-fouling property and high rejection towards ion contaminants. However, currently available membranes for FO application suffer from severe internal concentration polarization (ICP) due to their thick and low-porosity support layer, which leads to significant reduction in the efficiency of osmotic driving force. Therefore, innovations are urgently required in the design and fabrication of membranes that are structurally feasible for FO. This work has investigated the fundamental science of phase inversion and formation mechanism of cellulose ester membranes at the interface between polymer and casting substrate. It also explores the desired membrane preparation conditions for forward osmosis (FO) applications in seawater desalination. With the aid of positron annihilation spectroscopy (PALS) and molecular simulation, the similarity in physicochemical properties between the polymer and the substrate was found to play a significant role in determining the porosity of the bottom interfacial layer. The structure of the dense interfacial layer was also strongly dependent on membrane thickness and solvent composition. Experimental results surprisingly reveal that the original pore size of the as-cast membrane plays a critical role determining the final performance of the subsequent annealed membrane independently of annealing temperature and time. In addition, since a threshold pore size exists during annealing above which pores become difficult to down size, we have found that a thin dense selective layer integrally in an asymmetric membrane may not always be the best option for FO applications. A balanced membrane structure consisting of a thin porous support and a thin dense selective layer with a small structure parameter has been developed which shows low internal concentration polarization (ICP) in the FO process. There- fore, a relatively high water flux was observed when seawater was employed as the feed, indicating that the membrane has great potential for desalination.

68 POSTER 52

Polyelectrolyte Microcapsules for in Vitro Delivery of Basic Fibroblast Growth Factor

Zhen She1,2 1NUS Graduate School for Integrative Sciences and Engineering 2 Institute of Materials Research and Engineering (IMRE)

Basic fibroblast growth factor (bFGF) was loaded into microcapsules by a protective and effective Layer-by-Layer Encapsulation method. Low toxic and biodegradable polyelectrolyte shells with different thicknesses were coated and the release profiles of bFGF from microcapsules with different shell thicknesses were measured. The internal connection within concentration, shell thickness of microcapsules and their efficacy on promoting L929 cell proliferation was revealed in vitro.

69 POSTER 53

Semi-interpenetrating Network (SIPN) Proton Exchange Membranes Based on Poly(2,6-Dimethyl-1,4-Phenylene Oxide)

Fang Chunliu1,2 1Department of Chemical and Biomolecular Engineering 2NUS Graduate School for Integrative Sciences and Engineering

One of the barriers in the commercialization of the direct methanol fuel cells (DMFCs) is the high methanol permeability of current generation of perfluorosulfonated- based proton exchange membranes (PEMs); such as Nafion c . Alternative PEMs with high proton conductivity but lower methanol permeability can be the game-changer. This presentation summarizes our recent findings on the synthesis and properties of poly(2,6-dimethyl-1,4-phenylene oxide) (PPO)- based proton exchange membranes designed for fuel cell applications. A semi- interpenetrating polymer network (SIPN) is a variant of polymer alloys obtained by penetrating a linear or branched polymer into one or more cross-linked polymer network. The inter-chain entanglement can endow the SIPNs with forcible compatibility and mechanical stability. In our case, a series of PPO-based SIPN membranes were prepared by interpenetrating the sulfonated PPO moieties in a hydrophobic network of brominated PPO that was covalent cross-linked by ethylenediamine. Dynamic mechanical analysis (DMA) and differential scanning calorimetry (DSC) were used to evaluate the thermal transitions and mechanical relaxations of the composite membranes. The SIPN construction successfully inhibited methanol permeation through the membranes and improved the membrane dimensional stability by averting excessive swelling until 80 oC. Compared with Nafion c , the PPO-based SIPN membranes showed comparable proton conductivity and maximum power density but with a much lower methanol permeability. The PPO-based SIPN membranes have therefore acquired the basic physicochemical properties which are required for DMFC applications.

70 Poster Presentations: Medicine

71 POSTER 54

Regulation of Cullin RING E3 Ubiquitin Ligases by CAND1 In Vivo

Boon Kim Boh1, Yee Shin Chua2, Wanpen Ponyeam2, Thilo Hagen2 1NUS Graduate School for Integrative Sciences and Engineering 2Department of Biochemistry, Yong Loo Lin School of Medicine

Cullin RING ligases are multi-subunit complexes consisting of a cullin protein which forms a scaﬀold onto which the RING protein Rbx1/2 and substrate receptor subunits assemble. CAND1, which binds to cullins that are not conju- gated with Nedd8 and not associated with substrate receptors, has been shown to function as a positive regulator of Cullin ligases In vivo. Two models have been proposed to explain this requirement: (i) CAND1 sequesters cullin proteins and thus prevents autoubiquitination of substrate receptors, and (ii) CAND1 is required to promote the exchange of bound substrate receptors. Using mammalian cells, we show that CAND1 is predominantly cytoplasmically localized and that cullins are the major CAND1 interacting proteins. However, only small amounts of CAND1 bind to Cul1 in cells, despite low basal levels of Cul1 neddy- lation and approximately equal cytoplasmic endogenous protein concentrations of CAND1 and Cul1. Compared to F-box protein substrate receptors, binding of CAND1 to Cul1 In vivo is weak. Furthermore, preventing binding of F-box substrate receptors to Cul1 does not increase CAND1 binding. In conclusion, our study suggests that CAND1 does not function by sequestering cullins In vivo to prevent substrate receptor autoubiquitination and is likely to regulate cullin RING ligase activity via alternative mechanisms.

72 POSTER 55

Functional Eﬀects of a Novel BIM Polymorphism in Mediating Resistance to Tyrosine Kinase Inhibitors in Chronic Myelogenous Leukaemia

Juan Wen Chun1, Ng King Pan1, Ko Tun Kiat1, Axel Hilmer2, Charles Chuah Thuan Heng1, Ruan Yijun2, Ong Sin Tiong1 1Cancer and Stem Cell Biology Signature Research Program, Duke-NUS Graduate Medical School 2Genome Institute of Singapore, Agency for Science, Technology and Research

Most patients with chronic myelogenous leukaemia (CML) respond to therapy with BCR-ABL tyrosine kinase inhibitors (TKIs). However, about 15-20% of patients will eventually develop resistance to TKIs. Previously, we identified a novel polymorphism in the pro-apoptotic gene, BIM, which correlated with clinical resistance to TKIs. KCL22, a CML cell line that harbours the polymorphism, was used to investigate the functional effects of the BIM polymorphism. Initial experiments confirmed that KCL22 cells were highly resistant to TKIs when compared to cells without the polymorphism. Based on the gene structure of BIM, we predicted that the polymorphism would influence splicing between exons 3 and 4 in a mutually exclusive manner, an event that could affect cell death decisions since the pro-apoptotic BH3 domain is found only in exon 4. Consistent with this model, we found that KCL22 cells expressed increased exon 3- versus exon 4-containing transcripts compared to wildtype cells, a result mir- rored in CML patient samples. We next found that the decreased expression of exon 4-containing transcripts was associated with decreased protein expression of pro-apoptotic forms of BIM, including BIMEL, and that knockdown of exon-3 containing transcripts did not sensitize KCL22 cells to TKI-induced apoptosis. These results suggested that TKI-resistance in KCL22 cells was due to impaired expression of BH3-containing BIM isoforms. Consistent with this notion, we found that BH3 mimetics sensitized KCL22 cells to TKI-induced apoptosis. Our results offer mechanistic insights into how the BIM polymorphism mediates TKI-resistance; a resistance that we show can be overcome by BH3 mimetics.

73 POSTER 56

Regulation of C1q Expression at Transcriptional and Epigenetic Levels

Tan Shurong Carol1,2, Lu Jinhua2 1NUS Graduate School for Integrative Sciences and Engineering 2Department of Microbiology, Yong Loo Lin School of Medicine

C1q, a macromolecule assembled from three types of subunits (C1qA:C1qB:C1qC), has a vast array of physiological functions and implications in diseases. Most notably, a deficiency in C1q is associated with the development of systemic lupus erythematosus (SLE) for which the underlying mechanism is unclear. An interesting property of C1q is its production by dendritic cells (DCs) and macrophages, the two major types of antigen presenting cells (APCs). A de- fect in C1q production by these cells may significantly alter host tolerance to self-antigens. Hence, exogenous and endogenous factors that influence C1q production in these cells can potentially affect the onset of SLE. In mouse BMDCs, we observed the mRNAs of C1qA, C1qB and C1qC were co-ordinately regulated by microbial structures, hormones and cytokines. A notable feature is that the three C1q subunit genes are closely clustered on the chromosome, although how this may facilitate the coordinated expression of the three genes remains unknown. We postulate that the C1q genes behave as a gene cluster to achieve synchronized expression. To investigate the underlying mechanism, we first identified promoter and regulatory elements involved in the regulation of each C1q subunit genes. The transcriptional start sites (TSS) of the three C1q genes were determined and the putative promoter regions were each cloned into PGL3 luciferase reporter vector. All three promoters exhibited basal activity, suggesting that each C1q subunit gene has an independent promoter. However, only the activity of C1qB promoter was up-regulated by interferon-gamma (IFN-γ) even though all three endogenous C1q mRNA levels increased in BMDCs. An IFN-γ regulatory site was indeed identified 5’ to the C1qB basal promoter region.

74 POSTER 57

Structural Refolding of Hepatitis B Virus X Protein (HBx)

Oh Man Huan Veronica1,2, Ren Ee Chee1,3 1Department of Microbiology, Yong Loo Lin School of Medicine 2NUS Graduate School for Integrative Sciences and Engineering 3Laboratory of Immunogenetics, Singapore Immunology Network, Agency for Science Technology and Research

Chronic Hepatitis B virus (HBV) infection, which affects approximately 350 million people worldwide, is strongly associated with the development of hepatocel- lular carcinoma (HCC). However, the mechanisms underlying the oncogenicity of HBV infection are yet to be fully defined. Hepatitis B virus X protein (HBx), one of the viral proteins encoded by HBV, has been reported to be associated with the development of HCC. HBx is reported to be a multi-functional protein that modulates a wide variety of cellular pathways and also interacts directly with many host proteins. To date, however, the precise function and structure of HBx is still undefined. Since HBx does not bind directly to DNA and many of the cellular functions HBx modulates is via protein-protein interactions, it is important to elucidate the structure of HBx. HBx sequence was first cloned into pET-28a(+) vector and transformed into E. coli strain BL-21 cells for large scale bacterial expression. E. coli cells were then lysed and inclusion bodies containing the expressed HBx protein were washed and solubilized in 6M guani- dine denaturation buffer. The denatured HBx protein was then subjected to a wide variety of refolding conditions to refold the protein optimally. With the optimization of the refolding conditions, HBx protein was showed to acquire an unprecedented structural refolding, possessing a β-sheet secondary structure as demonstrated by its characteristic CD spectra. The refolded HBx protein can thus be purified and have its structure determined by nuclear magnetic resonance spectroscopy (NMR) or X-ray crystallography. The elucidation of the 3D structure of HBx protein would thus allow us to understand the spatial interactions between HBx and its binding proteins and to observe if HBx undergoes structural changes as it binds to its multiple cellular partners. The search of a structural homolog of HBx may also aid in the identification of the exact function of the multi-functional HBx protein.

75 POSTER 58

Identiﬁcation and Functional Analysis of AP2γ as a Novel Transcriptional Cofactor of Estrogen Receptor α in Breast Cancer

Si Kee Tan1, Zhen Hua Lin2, Cheng Wei Chang3, Kern Rei Chng4, Eu Leong Yong5, Edwin Cheung6 1O& G, Yong Loo Lin School of Medicine 2Cancer Biology and Pharmacology 3NUS Graduate School for Integrative Sciences and Engineering 4Genome Institute of Singapore, Agency for Science Technology and Research 5Department of Biological Sciences 6Computational and Mathematical Biology Group

Estrogen receptor (ER) transcription is fundamental to regulation of breast cancer development and progression. To understand the mechanism of ER transcription, we previously mapped the genomic landscape of ERα binding sites (ERBSs) in the breast cancer cell line, MCF-7, using high throughput ChIP- sequencing (ChIP-seq). As the transcriptional activity of ERα can be influenced through cooperation with multiple transcription factors, we are interested in uncovering potential novel ERα collaborating factors. Hence, we performed cofactor motif analysis by scanning the ERBSs identified by ChIP-seq with TRANSFAC motif matrices. Our analysis revealed binding sequences of AP2 family of transcription factors (GCCYNNGGS) as significantly enriched in the ERBSs. The AP2 family of transcription factors orchestrate a variety of cellular processes, including cell growth, cell adhesion and tissue differentiation. AP2γ (TFAP2C), a member of the AP2 family, was reported to be over-expressed in breast carcinoma and recently shown to promote breast tumour cells proliferation. However, little is known on how it regulates transcription in breast cancer. Here, using a combination of RNA interference, ChIP and Chromosome conformation capture (3C) assays, we aim to study how AP2γ regulates ERα transcription of RET (rearranged during transfection), an estrogen-responsive gene, in MCF-7 cell line.

76 POSTER 59

Understanding the Regulatory Network of Androgen Receptor and TMPRSS2-ERG Fusion Protein in Prostate Cancer Progression

Chng Kern Rei1,2, Tan Si Kee1,2, Chang Cheng Wei1,2, Yang Chong1,2, Hong Shuzhen1, Edwin Cheung1,2 1Genome Institute of Singapore, Agency for Science Technology and Research 2NUS Graduate School for Integrative Sciences and Engineering

Deregulation of the AR (Androgen Receptor) transcriptional network is a common hallmark in prostate cancers. AR is a master transcription factor that orchestrates a circuitry of genes mediating cellular proliferation, differentiation, motility and survival. To achieve its precise transcriptional role, AR needs to co-operate specifically with a plethora of co-factors. In prostate cancers, AR transcription collaborators are frequently aberrantly expressed, altering the AR signaling pathway to one that promotes oncogenesis. Recently, it was discovered that the majority of prostate cancers harbour a recurrent gene fusion between TMPRSS2, an AR target gene and ERG, a member of the ETS family of transcription factors. Consequently, ERG is induced upon androgen stimulation. To study the potential cancer-specific transcriptional collaboration between AR and ERG, we adopted a ChIP-Seq approach. We observed increased recruitment of ERG to a substantial portion of AR binding sites after androgen stimulation, indicative of its role as an AR transcriptional collaborator. ERG was found to directly repress AR expression. In addition, ERG was also found to act as an inhibitor of AR transcriptional activity. Currently, our work suggests that over-expression of ERG might impede AR-induced epithelial differentiation and enhance epithelial mesenchymal transition (EMT) in prostate cancer cells, thereby conferring a more aggressive and invasive phenotype.

77 POSTER 60

Bcl-2 Modulates Resveratrol-induced ROS Production by Regulating Mitochondrial Respiration in Tumor Cells

Ivan Cherh Chiet Low1,2, Shazib Pervaiz1,2,3,4 1Department of Physiology, Yong Loo Lin School of Medicine 2NUS Graduate School for Integrative Sciences and Engineering 3Cancer ans Stem Cell Biology Program, Duke-NUS Graduate Medical School 4Singapore-MIT Alliance

Resveratrol is a naturally occurring flavanoid with potent apoptosis inducing activity against human tumor cells. We investigated the effect of resveratrol on human leukemia cell lines, in particular its ability to induce intracellular reactive oxygen species production and the effect of Bcl-2 overexpression on this model. Exposure of CEM cells to increasing concentrations of resveratrol (0-50µM) resulted in an increase in mitochondrial superoxide production, decrease in mitochondrial biogenesis and transmembrane potential, and a concomitant decrease in cell viability. Whereas overexpression of Bcl-2 increased mitochondrial oxygen consumption and complex IV activity, CEM/Bcl-2 cells responded to the increased mitochondrial oxidative stress induced by resveratrol by significantly reducing mitochondrial respiration, complex IV activity and superoxide production, and promoted cell survival. The inhibitory effect of Bcl-2 on resveratrol-induced mitochondrial superoxide production is further cor- roborated by the neutralization of this regulatory effect upon siRNA mediated gene silencing of Bcl-2. These data provide evidence implicating mitochondrial metabolism in the anti-cancer activity of resveratrol, and underscore a novel regulatory role of Bcl-2 against exogenous oxidative stress through its ability to fine tune mitochondrial respiration, and by doing so maintaining mitochondrial superoxide at a level optimal for survival.

78 POSTER 61

A Novel Role for RUNX3 in the Regulation of IL23A

Yit Teng Hor1,2, Dominic Voon Chih Cheng1, Jason Koo Kin Wai1, Huajing Wang1, Yoshiaki Ito1,2,3 1Cancer Biology Program, Cancer Science Institute of Singapore 2NUS Graduate School for Integrative Sciences and Engineering 3Institute of Molecular and Cell Biology, Agency for Science, Technology and Research

RUNX3 is a prominent tumour suppressor in gastric epithelium where its inactivation is observed in ¿80% of human primary gastric cancers. As an important regulator of gastric epithelial cell growth and apoptosis, we have previously reported that RUNX3 regulates key target genes, p21 and Bim1. However, the full genetic programme maintained by RUNX3 in the gastric epithelium remains to be fully elucidated. As a step towards this, we conducted an expression microarray study, which measured transcriptomic changes following the re-introduction of RUNX3 into a non-expressing cell line. Here, we report the identification of a novel RUNX3 target gene, IL23A. IL23A encodes the unique subunit of Interleukin-23 (IL-23) known to play a key role in immune surveillance against pathogens in the gastrointestinal tract. We posit that RUNX3 exercises its tumor suppressive function in part through a direct regulation of this gene. In our validation study, we observed the induction of IL23A by RUNX3 across multiple cancer cell lines, implicating an important role. Through reporter assays, we demonstrated the functions of three RUNX binding sites on the IL23A proxi- mal promoter. In this assay system, we observed the transactivation of IL23A promoter by all three mammalian RUNX members, suggesting a degree of in- terchangeability in their regulation of this gene, possibly in different cell types. In vitro binding of RUNX3 on the RUNX binding sites was demonstrated using mobility shift assay and confirmed by chromatin immunoprecipitation. Lastly, we performed RNAi knockdown of RUNX factors in the established cell model to demonstrate their involvement in the regulation of IL23A expression and IL- 23 secretion. Given the importance of IL-23 in mucosal immunity, we postulate that RUNX proteins play a multi-facet role in maintaining the homeostasis in the mucosal barrier and immune surveillance in the gut.

79 POSTER 62

Characterization of the Role of E7 in Transcriptional Regulation of Mitotic Genes

Pang Chai Ling1, Teissier Sebastien2, Thierry Francoise2 1Department of Microbiology, Yong Loo Lin School of Medicine 2Institute of Medical Biology, Agency for Science Technology and Research

Human Papillomavirus (HPV) is etiologically associated with more than 99% of cervical cancer. Malignant transformation of keratinocytes infected by HPV has been attributed to oncogenic activities of E6 and E7. E6 mediates p53 degradations whereas E7 stimulates cell cycle progression via pRB inactivation. Previous studies have demonstrated that E7 can up-regulate E2F target genes and promote S-phase entry by subverting pRB/E2F pathway. Recent microarray findings implied that E7 also plays a significant role in the modulation of mitotic genes but the molecular mechanism remains elusive. This data was validated by our PCR array experiment and the results showed that E7 has profound effect in cell cycle regulation. In addition, B-Myb and FoxM1 are E2F target genes as well as the major transcription factors for regulation of mitotic genes. We have characterized role of B-Myb and FoxM1 in cervical carcinogenesis through siRNA-mediated depletion of gene expression and this data indicates that B-Myb plays a more dominant role in regulation of mitotic gene expression. E7 can promote mitotic entry via downstream effectors, such as B-Myb and FoxM1 but we do not exclude the possibility that E7 may exert direct effects on gene regulation of mitotic genes. We also found that E7 can interact and co-localize with B-Myb in nucleus from immunoprecipitation and immunofluorescence assay. In addition, we have performed chromatin immunoprecipitation and we confirmed that E7 can bind to promoter region of mitotic genes. Collectively, our results suggest that E7 can be directly recruited to promoter of mitotic genes in association with B-Myb, FoxM1 and/or other putative interactors. This understanding of interplay between E7, B-Myb and FoxM1 would enable us to fully delineate the underlying mechanism of malignant transformation of HPV infection in order to develop the novel therapeutic targets for combating cervical cancer.

80 POSTER 63

Identiﬁcation of Recurrent Regions of Copy Number Variants Across Multiple Individuals

Teo Shu Mei1,2, Agus Salim1,2, Yudi Pawitan1,2 1Department of Epidemiology and Public Health 2NUS Graduate School for Integrative Sciences and Engineering

Identification of common copy-number polymorphisms regions using high density SNP array. SNP arrays and array comparative genomic hybridization (aCGH) arrays are widely used technology platforms for CNV detection. The CNVs are usually detected per sample, and because of the high noise level in the intensity values, the boundaries of the detected CNVs tend to vary among individuals. However, common CNV regions are likely to occur at the same genomic location across different individuals. Common algorithms used with SNP array data, for identifying individual CNV regions, such as PennCNV, report the log Bayes factor as a confidence score for each identified CNV; these scores provide evidence of the reliability of a CNV within an individual. Previous methods of detecting common regions have failed to incorporate the confidence scores, mainly because they were primarily designed for aCGH data. By not incorpo- rating the use of individual specific confidence scores, it means that all samples contribute equally to the statistic used to identify the common regions, but in fact, there is inter-sample variability, where some individual regions are more likely to be true/false positives. We develop three new approaches for identifying common CNV regions that are recurrent to all or an unknown subset of subjects. The methods take segmented data as the input. The first method es- timates a statistic based on the frequency of occurrence of reliable CNVs, where reliability is determined by high confidence scores. The second method is based on a weighted frequency of occurrence of CNVs, where the weights are determined by the confidence scores. The last method is motivated by the fact that we sometimes observe partially overlapping CNV regions as a mixture of two or more distinct subregions; it is based on a clustering algorithm applied to the common regions found in the first or second method. The identified common regions can then be used for downstream analysis such as group comparisons in association studies.

81 POSTER 64

Dengue Virus Neutralization in Human Monocytes

Chan Kuan Rong1,2, Zhang Li-Xin3, Tan Hwee Cheng1, Brendon Hanson3, Mariano A Garcia-Blanco1, Ooi Eng Eong1 1Duke-NUS 2NUS Graduate School for Integrative Sciences and Engineering 3DSO National Laboratories

Dengue affects 50-100 million worldwide, with about half a million hospital- ized cases annually. Humoral immunity response to the virus can result in two possible extreme outcomes: either virus neutralization which protects the host from dengue infection, or enhancement of infection in monocytes which results in increased disease severity. However, the determinants of successful virus neutralization in the context of Fc-gamma receptor bearing cells, which are targets of the virus, is incompletely understood. We investigated the early intracellular events of dengue immune complexes following interaction with THP-1 cells to understand how virus-antibody complexes are neutralized in human monocytes. Using a mouse-human chimeric antibody against DENV-2, we observed that antibody concentration affects the size of the immune complexes formed, which results in different Fcγ-receptor (FcγR) engagement. Larger immune complexes appear to cross-link FcγRIIB, which inhibits internalization of immune complexes in monocytes. Increase in internalization was observed when the antibody concentration was reduced, as immune complex size results in di- minished cross-linking of FcγRIIB. Collectively, our studies provide a novel tool to investigate early intracellular events between antibody-virus complexes and monocytes, and provide some mechanistic insights into dengue virus neutralization in human monocytes.

82 POSTER 65

Sustained High Levels of IL-6 Contribute to the Pathogenesis of Enterovirus 71 in a Neonate Mouse Model

Khong Wei Xin1, Damian G. W. Foo1, Tan Eng Lee2, Sylvie Alonso1 1Department of Microbiology, Immunology Programme, Yong Loo Lin School of Medicine 2School of Chemical and Life Sciences, Singapore Polytechnic

Enterovirus 71 (EV71) is the major causative agent of Hand, Foot and Mouth Disease (HFMD) in young children, and has been consistently associated with the most severe complications of the disease, which include central nervous system inflammation, and pulmonary edema. Increasing frequency and amplitude of EV71 outbreaks have raised awareness and concerns worldwide. Previous reports proposed that overwhelming virus replication combined with the induction of massive pro-inflammatory cytokines is responsible for the pathogenicity of EV71. Specifically, elevated IL-6 levels were observed consistently in patients and strongly correlated with disease severity. In this study, we showed in the neonate mouse model that sustained high levels of IL-6 produced upon EV71 infection are detrimental to the host, leading to severe tissue damage, and even- tual death to the animals. Administration of anti-IL-6 neutralizing antibodies after the onset of the clinical symptoms successfully improved survival rate and clinical score of the infected hosts. In addition, compared to non-treated controls, anti-IL-6 treated mice displayed reduced tissue damage and absence of splenic atrophy. Upon anti-IL-6 treatment, transient markedly increase in IL- 10 levels was measured. Furthermore, there was no significant difference in virus titers between anti-IL-6 treated and non-treated mice, indicating that the anti-IL-6 antibody-mediated protection is independent of the virus load. Our findings thus demonstrated that IL-6 plays a major role in EV71-induced im- munopathogenesis. Furthermore, as there is still neither vaccine nor treatment available against EV71, anti-IL-6 antibody treatment may represent a possible therapeutic approach to prevent from the most severe complications of the disease.

83 POSTER 66

Role of Rac1 in Regulating Bcl-2 Mediated Chemoresistance and Pro-oxidant State in Tumour Cells

Kang Jia1,2, Rathiga Velaithan2, Jayshree L. Hirpara2, Catherine Brenner3, Marie Veronique Clement4, Shazib Pervaiz1,2,5,6 1NUS Graduate School for Integrative Sciences and Engineering 2Department of Physiology, Yong Loo Lin School of Medicine 3Facult´ede Pharmacie, Universit´eParis 4Department of Biochemistry, Yong Loo Lin School of Medicine; 5Duke-NUS 6Singapore-MIT Alliance

We have previously reported that Bcl-2 expression resulted in an increase in intracellular superoxide anion and that a dominant negative mutant of the small GTPase Rac1 sensitized Bcl-2 expressing cells to apoptosis. Here we report that silencing and functional inhibition of Rac1 blocks Bcl-2 mediated increases in intracellular and mitochondrial superoxide levels in tumor cells. We provide evidence that this eﬀect is mediated via speciﬁc interaction between the two proteins using coimmunoprecipitation, confocal and electron microscopy, as well as GST-fusion proteins. Analysis of the sub-cellular localization of these proteins revealed increased association of Bcl-2 and mitochondrial Rac1 in Bcl-2 overexpressing cells. This interaction can be blocked in vitro and in vivo by the BH3 mimetics, HA14-I and BH3-I, as well as by synthetic Bcl-2 BH3 domain peptides. That this interaction is functionally relevant is supported by the ability of the Bcl-2 BH3 peptide to inhibit intracellular superoxide production as well as overcome drug resistance in Bcl-2 overexpressing cells. Lastly, using patient derived primary tissues, the interaction was observed only in cancerous tissues with marked overexpression of Bcl-2 and not in peripheral blood leukocytes or noncancerous primary tissue. These data provide a novel facet in the biology of Bcl-2 with potential implications for targeted anti-cancer drug design.

84 POSTER 67

Study on Wrinkly Skin Syndrome (WSS) using induced Pluripotent Stem Cells (iPSCs) model

Zhou Fan1,2,3, Zhang Jinqiu1, Nathalie Escande-Beillard1, Bruno Reversade1, Fu Xinyuann1,2,3, Alan Colmann1,2 1Institute of Medical Biology, Agency for Science Technology and Research 2Department of Biochemistry 3NUS Graduate School for Integrative Sciences and Engineering

Wrinkly skin syndrome (WSS; MIM278250), also called Autosomal Recessive cutis laxa type II (ARCRL2; MIMI219100), is an autosomal recessive disor- der that is characterized by wrinkly skin (hands, feet and abdomen), decreased elasticity of the skin, multiple skeletal abnormalities, microcephaly, and men- tal retardation (Casamassima et al. 1987). The latest report suggested that WSS was caused by different mutations of PYCR1 (Reversade et al. 2009). Because WSS is exceptionally rare, biopsy material is not readily available and the impact of the PYCR1 mutation on different cell types is difficult to assess. However, with the advent of induced pluripotent stem cells (iPSCs), multiple patient-specific cell types can be made available. This provides us a new platform to model many human diseases (Colman and Dreesen, 2009). In our study, we established an iPSC disease model for WSS. WSS fibroblasts were firstly reprogrammed into iPSCs using retrovirus-based method. For three WSS cell lines, we got at least two different colonies for each cell line. To verify the identity of all these colonies, various assays were performed to characterize iPSCs, including expression study, methylation status study, karyotype analysis, teratoma formation assay. After completing the characterization of the iPSC lines, currently, we are trying to investigating the cellular defects during the disease development in the iPSC model, and hoping to uncover the molecular mechanism underlying WSS disease.

Reference: Casamassima AC, Wesson SK, Conlon CJ, et al. Wrinkly skin syndrome: phenotype and additional manifestations. Am. J. Med. Genet. 27, 885-893 (1987). Colman A, Dreesen O. Pluripotent stem cells and disease modeling. Cell Stem Cell 5, 244-247 (2009). Reversade B, Escande-Beillard N, Dimopoulou A, et al. Mutations in PYCR1 cause cutis laxa with progeroid features. Nat Genet. 41, 1016-1021(2009)

Poster Presentations: Physics

87 POSTER 68

Quasi-Freestanding Epitaxial Graphene on SiC via Fluorine Intercalation from a Molecular Source

Wong Swee Liang1,2 1Department of Physics 2NUS Graduate School for Integrative Sciences and Engineering

Epitaxial graphene on SiC(0001) is a promising route towards large scale fabrication of graphene devices but is limited by the presence of an interacting substrate. Graphene-substrate√ √ interaction is mainly mediated by the interface SiC(0001) 6 3 × 6 3 R30◦ layer (buffer layer). Intercalation of the buffer layer to form quasi-freestanding epitaxial graphene has been performed using sources such as H2 to minimize this interaction. However, detailed STM studies have not been conducted on these quasi-freestanding epitaxial graphene or its formation process. In this report, fluorine intercalation of the buffer layer was carried out using fluorinated fullerenes, C60F48, as a source of fluorine. The process of graphene formation via fluorine intercalation and its properties was investigated using Low Temperature Scanning Tunneling Microscopy (LT-STM), Scanning Tunneling Spectroscopy (STS) and Photoemission Spectroscopy (PES). Quasi- freestanding epitaxial graphene with dilute fluorination was achieved√ after√ intercalation and confirmed by the absence of the underlying SiC 6 3 × 6 3 R30 reconstruction layer and also the presence of novel structures observed for the first time under LT-STM. PES reveal that the fluorine involved in the intercalation remains in the substrate, possibly as a passivation layer between the freestanding epitaxial graphene—SiC interface. The mechanism underlying the process will be discussed in detail with respect to the findings.

88 POSTER 69

Structure and Mechanical Properties Study of Bombyx Mori Silkworm Silk Fibrils by Atomic Force Microscope and X-ray Diﬀraction

Deng Qinqiu1,2 1Department of Physics 2NUS Graduate School for Integrative Sciences and Engineering

The aim of this project is to unravel the micro-structure and mechanical properties of the Bombyx mori silk fibril through atomic force microscopy and x-ray diffraction. Silk is a material with better properties than most of man-made fibers, and the study of the structure of silk has been a quite hot area. How- ever, less is known about the structure and mechanical properties of the basic unit-silk fibril,which interacts with each other to form the final silk fiber. So, our goal is to use the atomic force microscpe to investigate the mechanical design of the silk fibril, and combining the structure information from the x-ray diffraction, we hope to figure out the structure model of the silk fibril andob- tain information about amino acid organization in the silk andits corresponding structure.

89 POSTER 70

Nanoparticles Fractionation using Aligned Carbon Nanotube Array

Xiaodai Lim1,2 Hairuo Xu3, Yi Hui Nicole Chew4, Yi Hui Phua4, Edbert Jarvis Sie5, Tze Chien Sum5, Guo Hao Chia4,2, Wee Shong Chin3,∗, Chorng-Haur Sow2,∗ 1NUS Graduate School for Integrative Sciences and Engineering 2Department of Physics 3Department of Chemistry 4Dunman High School 5Division of Physics & Applied Physics, School of Physical & Mathematical Sciences, Nanyang Technological University

A technique utilising the capillary-assisted sieving capability of carbon nan- otubes (CNTs) to achieve fractionation of nanoparticles of small size distribution is presented. By dipping aligned CNT arrays into solution comprising different sized quantum dots (QDs), size-selective gradient decoration of QDs onto CNTs is achieved. The fractionating capability of CNTs is also demonstrated for poly- dispersed manganese doped zinc sulphide nanoparticles and QDs of varying sizes and chemical compositions, which we attribute to the size-selective sieving effect of CNTs. By controlling the terminating point for the flow of QDs across the CNT array, QDs size specific CNT/QDs hybrid structure is achieved.

90 POSTER 71

Experimental and Computational Studies of Fibroblast Migration on Compliant Substrates

Yip Ai Kia1, Chiam Keng Hwee2, Paul Matsudaira3 1NUS Graduate School for Integrative Sciences and Engineering 2Biophysics, Institute of High Performance Computing, Agency for Science Technology and Research 3Department of Biological Sciences

The stiffness of the extracellular matrix which biological cells exists in physiolog- ically varies depending on the cells’ location, and it has been shown that cells can sense and respond to differences in stiffness during differentiation and migration. However, the mechanism which regulates these differences in cell behaviour is not well understood. NIH3T3 fibroblasts were cultured on polyacrylamide substrates of different stiffness and fibronectin coating, and cell migration speed was calculated. It was found that cells showed maximal speed at intermediate stiffness (7-13kPa). On soft substrates (≤ 7kPa), optimal fibronectin concentration for maximal cell speed occurs at 75µg/ml, whereas on stiffer substrates, optimal concentration occurs at 25µg/ml. When the focal adhesion protein vinculin was stained, total amount of vinculin was not significantly changed when substrate stiffness is increased. However, vinculin form structures which increase in size with increasing stiffness. We hypothesized that increasing substrate stiffness do not affect total number of cell-substrate adhesions, but increases clustering of bonds which reinforces adhesion strength. A computational model was used to simulate cell detachment with various spatial distributions of adhesion bonds to the substrate, while keeping the number of cell-substrate adhesions constant. Simulation results showed that for the same detachment force, adhesion lifetime is shorter when bonds are arranged in small clusters. However, when clusters are larger, due to cooperatively between neighbouring bonds, adhesion cluster lifetime is increased. We argued that on stiff substrate, larger focal adhesion size resulted in stronger adhesion to the substrate, allowing the cell to exert more traction forces to move forward as compared to cells on soft substrates. However, when adhesion to the substrate is too strong, adhesion lifetime is increased, thus slowing down migration.

91 POSTER 72

Dynamic-based Structure Measures on Complex Networks

Zhu Guimei, Li Baowen Department of Physics

Network topology structures play a crucial role in determining the emergence of collective dynamical behaviour. It is the cornerstone for understanding the relationship between structures, functions and dynamics of complex networks. We study the structural characteristics of complex networks using the representative eigenvectors of the adjacent matrix. The probability distribution functions of the components of the representative eigenvectors are proposed to describe the localization on networks where the Euclidean distance is invalid. Also, comparison of cellular networks can provide insights into biological understanding and therapeutics. Dynamics on biological networks, as the bridge between structures and functions, occur generally from micro- to macro- struc- tural scales. Some measures of networks are proposed such as degree distribution, shortest pathway, graphlet distribution and fractal, but how to describe simultaneously the structural patterns at diﬀerent scales is still an open problem. For an electron moving in a large molecule, the eigenstates of the tight-binding Hamiltonian represent from low to high energy are used as probes of the structural characteristics from macro- to micro- scales. Localization properties are used to characterize the eigenstates. Being a measure of network structures, the structure-induced localization may also have potential applications in understanding the electronic properties of materials such as conductive polymers and carbon nanonets. The intrachain windings in conductive polymers can introduce long-range edges into the original one dimensional system, resulting in nontrivial network structures.

92 Special thanks to

• Benjamin Mate Gyori • Inosha Wickrama • Joanne James • Manickaratnam Ranjan • Sampath Jeewantha Wijesinghe • Yap Wen Lynn Notes