3rd NGS Student Symposium February 28, 2011 · either oral or poster presentations and the...

3rd NGS Student Symposium

February 28, 2011

Venue supported by:Shaw Foundation Alumni House

Organizing CommiteeLin 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 logoAs a computational linguist, I am interested in the application of artificial intelligenceto 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 wordcloud from the content of the NGS website. Notice how the algorithm automaticallyindentifies 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 DriveSingapore 119244

Welcome

NGS Scholars’ Alliance warmly welcomes you to the 3rd NGS Student Sym-posium held in the Shaw Foundation Alumni House. NGS Scholars’ Allianceis the official student body for NGS students. It was established in December2005 to serve as a platform for intellectual exchange and interaction among allNGS scholars. NGS Student Symposium is an annual conference organised bythe NGS Scholars’ Alliance. The aims of the symposium are to foster effectivecommunication between NGS students and their supervisors, give NGS studentsan opportunity to showcase their research findings and promote interaction be-tween NGS students and renowned scientists of different fields.

Since its inception in 2008, the NGS Student Symposium has grown fromstrength to strength. This year, we received a total number of 78 abstractssubmitted for oral and poster presentations. This would not have been possiblewithout the participation of all NGS students who have submitted abstracts foreither oral or poster presentations and the organizing committee would like tothank all participants for their efforts.

To enhance technical information exchange among researchers of similarfields, we have segmented the symposium into two sessions; First, the Phys-ical Sciences and Engineering and second, the Chemistry, Biology and MedicalSciences. This year, it is our great privilege to have with us, Professor AnthonyZee and Professor Ding Jeak Ling, as our honorary invited speakers.

We would like to take this opportunity to extend our heartfelt gratitudeto the NUS Office of Alumni Relations for kind sponsorship of this venue. Inaddition, we would like to thank Ms. Ivy Wee, Ms. Irene Chuan and Ms. AngelaPoon for their constant support and invaluable advice.

All in all, this symposium is dedicated to encourage networking and scientificexchange among research students and professors. It would have been impossiblewithout your contribution, feedback and constructive suggestions. If you haveany suggestion or a keen interest in helping NGS organize quality meetings suchas 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 fruitfulconference!

NGS Scholars’ [email protected]

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Programme

08:00 – 09:00 Registration and poster setup

Session 1: Physical Sciences and Engineering

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

09:05 – 09:50 The importance of interdisciplinary perspective intheoretical physicsProfessor Anthony Zee, Ph. D.Professor of PhysicsDepartment of PhysicsUniversity of California, Santa Barbara

09:50 – 10:00 Q & A

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

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

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

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

12:30 – 13:30 Lunch and poster session

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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 SciencesNational University of Singapore

14:20 – 14:30 Q & A

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

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

15:30 – 16:00 Presentation 5Linc-ing Neurogenesis – Long Non-coding RNAs DetermineNeural Stem Cell FateNg Shi Yan

16:00 – 16:30 Presentation 6eCEO:An efficient Cloud Epistasis cOmputing model ingenome-wide association studyZhengkui Wang

16:30 – 17:00 Prize presentation and photo taking

List of Posters

1 CD155 Expression by TLR Agonists on Antigen-Presenting CellsDepends on NF-κB and IRFs . . . . . . . . . . . . . . . . . . . . 14Neha Kamran

2 Macromolecular Crowding & Stem Cell Differentiation . . . . . . 15Rafi Rashid, Michael Raghunath, Thorsten Wohland

3 The Characterization of D-Ptx1 and its Role in Drosophila CellFate Specification . . . . . . . . . . . . . . . . . . . . . . . . . . . 16Joanne Toh, Murni Tio, Gerald Udolph

4 Integrating Multiple Signals in Immune Modulation . . . . . . . 17Tan Suet Ting Rebecca, Ding Jeak Ling

5 Characterization and Long-term Homing Potential of PregnancyAssociated Progenitor Cells (PAPCs) in a Murine Model of Fe-tomaternal Microchimerism . . . . . . . . . . . . . . . . . . . . . 18Yeo Ailing

6 Using Stem Cell-derived Insulin-producing Cell Lines to Delin-eate Unique Biological Pathways as Therapeutic Targets . . . . . 19Ronne Yeo Wee Yeh, Lim Sai Kiang

7 Identification and Characterization of the Vertebrate Motile Cil-iome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20Deepak Babu

8 An Analysis of a Pak4 Signaling Complex . . . . . . . . . . . . . 21Widyawilis Selamat, Edward Manser

9 A Novel Anticoagulant from Amblyomma variegatum (TropicalBont Tick) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22Angelina Tan, Maria Kazimirova, RM Kini

10 CENTDIST: Discovery of Co-associated Factors by Motif Distri-bution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23Chang Cheng Wei, Zhang Zhizhuo, Goh Wan Ling, Cheung ChongWing, Sung Wing King

11 Structural and Functional Study of a Spider Silk Protein-AcSp1 . 24Wang Shujing

12 Natural Variant Forms of C1q . . . . . . . . . . . . . . . . . . . . 25Leong Jing Yao

13 Development of Living Color Transgenic Medaka for Biomonitor-ing Aquatic Contamination . . . . . . . . . . . . . . . . . . . . . 26Ng Hwee Boon Grace

14 EvpP is a Unique Protein in T6SS of E. tarda . . . . . . . . . . . 27Hu Wentao

15 Novel Approaches for the Identification of Viral Epitopes Asso-ciated with Asian HLA Employing Conditional Ligands . . . . . 28Cynthia Xin Lei Chang, Ming Yan Or, Kai Yee Toh, Anthony T Tan,

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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 . . . . . . . . . . . 29Lim Yan Ting, Paul A MacAry, Gan Yunn Hwen

17 Altered Cellular Iron Metabolism During Senescence in IMR-90Fibroblasts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30Hendry S. Cahaya, David W. Killilea, Sebastian Schaffer, Bruce Ames,Barry Halliwell

18 Live Ratiometric Ca2+ Imaging in a Zebrafish Model of SpinalMuscular atrophy . . . . . . . . . . . . . . . . . . . . . . . . . . . 31Kelvin See, Christoph Winkler

19 PRL-3 phosphatase downregulates beta-catenin, a Wnt-signallingcomponent, in vitro and in vivo . . . . . . . . . . . . . . . . . . . 32Abdul Qader Al-aidaroos, Wang Hai He, Zeng Qi

20 EGF signaling pathway involvement in regulating keratin dynam-ics in an Epidermolysis Bullosa Simplex disease model . . . . . . 33Tong San Tan, John E.A. Common, Cedric Badowski, E. Birgitte Lane

21 Cell Cycle Lipidomics . . . . . . . . . . . . . . . . . . . . . . . . 34Jing Yan Lim, Markus Wenk

22 Synthesis of Heterometallic Cobalt Clusters and Their MagneticProperties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36Pei Wang and T.S. Andy Hor

23 Mechanism of Hydrogen Peroxide Induced Keratinocyte Cell SheetMigration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37Loo Eng Kiat, Alvin, Ho Rongjian, Wong Yee Ting, Barry Halliwell

24 Targeting the “Turtle” – Metabolic Labelling of Inositol lipids . . 38Shareef Mohideen Ismail, Sandip Pasari, Martin Lear, Markus Wenk

25 Designing Artificial Team-mates for Increased Affiliation . . . . . 40Tim Merrit, Kevin McGee

26 Rereadability in Procedural Hypertext Fiction . . . . . . . . . . 41Alex Mitchell

27 State Space Reduction for Linearizability Checking . . . . . . . . 42Zhang Shaojie

28 Non-negative Matrix Factorization with KL Divergence CriterionEquals Maximum Likelihood Decomposition . . . . . . . . . . . . 43Wang Xuancong, Sim Khe Chai

29 Domain Adaptation for Semantic Role Labeling in the BiomedicalDomain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44Daniel Dahlmeier, Hwee Tou Ng

30 SOPRAN: Scalable Online Proactive Re-optimization in VirtualMachine Management with Dynamic Workloads . . . . . . . . . . 45Jian Zhou, Lei Shi, Kian-Lee Tan

31 Mesoporous Poly-Melamine-Formaldehyde for Reversible CarbonDioxide Adsorption . . . . . . . . . . . . . . . . . . . . . . . . . . 48Mei Xuan Tan, Yugen Zhang, Jackie Y. Ying

32 Surface-Functionalized and Surface-Functionalizable Poly(vinylidenefluoride) Graft Copolymer Membranes via Click Chemistry andAtom Transfer Radical Polymerization . . . . . . . . . . . . . . . 49Cai Tao, Kang En-tang

33 Electrospun Nanofibrous Composite for Osteogenic Differentia-tion of Mesenchymal Stem Cells . . . . . . . . . . . . . . . . . . . 50Luong T. H. Nguyen, Susan Liao, Seeram Ramakrishna, Casey K Chan

34 Biological Adhesives as Initiator Anchors for Surface-initiatedPolymerization in the Preparation of Multifunctional “Green”Surfaces . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51Wenjing Yang, Gary H. Dickinson, Serena Lay-Ming Teo, Tao Cai,Koon-Gee Neoh, En-Tang Kang

35 Nonlinear Control of Underactuated Systems With Applicationsto Autonomous Robotics . . . . . . . . . . . . . . . . . . . . . . . 52Guo Zhaoqin

36 Analysis and Control of Closed Quantum Systems Based on Real-valued Dynamics . . . . . . . . . . . . . . . . . . . . . . . . . . . 53Xue Zhengui, Lin Hai, Lee Tong Heng

37 A Real-time Reconstruction Approach for AR-based Applications 54Jiang Shuai, Ong Soh Khim, Andrew Y. C. Nee

38 Image Correlation Spectroscopy as a Tool for Microrheology ofSoft Materials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55Nicholas Agung Kurniawan, Chwee Teck Lim, Raj Rajagopalan

39 Metabolic Networks Based Approach for Understanding Struc-tural Organization Principles of Essential Genes . . . . . . . . . . 56Ma Jing

40 Toxicant-induced Sexual Dimorphic Responses in Zebra Fish MetabolicSystem . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57Zhang Xun

41 Remote Maintenance using Augmented Reality Technology . . . 58Zhu Jiang, Andrew Yeh-Ching Nee, Patricia Soh-Khim Ong

42 Augmented Reality 3D Design Space . . . . . . . . . . . . . . . . 59Ng Lai Xing

43 Electrophysiological consequence of genetic perturbation in gas-trointestinal diseases — a computational investigation . . . . . . 60Poh Yong Cheng, Martin Buist

44 Magnetism and Magnetotransport Studies in Ge0.9Mn0.1Te . . . 61Lim 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 . . . . . . . . . . . . . . . 62Liu Lei, K K Tan, S Huang, T H Lee

46 Morphological Tuning, Self-assembly and Optical Properties ofIndium Oxide Nanocrystals . . . . . . . . . . . . . . . . . . . . . 63Zhang Shuangyuan, Ye Enyi, Han Mingyong

47 Genome-scale Modeling and in silico Analysis of Pichia pastorisfor Biotechnological Applications . . . . . . . . . . . . . . . . . . 64Chung Kai Sheng, Bevan, Lee Dong-Yup

48 Quantitative Analysis of Surface Pluripotent Marker Expressionon Human Embryonic Stem Cells (hESCs) during DifferentiationUsing hESC - Specific Antibodies . . . . . . . . . . . . . . . . . . 65Lesley Y Chan, Evelyn KF Yim, Andre B Choo

49 Hybrid Control for Unmanned Helicopters . . . . . . . . . . . . . 66Ali Karimoddini, Lin Hai, Ben Chen, T. H. Lee

50 Soft Tissue Discrimination in Magnetic Resonance ElastographyUsing a New Elastic Level Set Model . . . . . . . . . . . . . . . . 67Li 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 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68Zhang 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 . . . . . . . . . . . . . . . . . . . . . . . 69Zhen She

53 Semi-interpenetrating Network (SIPN) Proton Exchange Mem-branes Based on Poly(2,6-Dimethyl-1,4-Phenylene Oxide) . . . . 70Fang Chunliu

54 Regulation of Cullin RING E3 Ubiquitin Ligases by CAND1 InVivo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72Boon Kim Boh, Yee Shin Chua, Wanpen Ponyeam, Thilo Hagen

55 Functional Effects of a Novel BIM Polymorphism in MediatingResistance to Tyrosine Kinase Inhibitors in Chronic MyelogenousLeukaemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73Juan Wen Chun, Ng King Pan, Ko Tun Kiat, Axel Hilmer, CharlesChuah Thuan Heng, Ruan Yijun, Ong Sin Tiong

56 Regulation of C1q Expression at Transcriptional and EpigeneticLevels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74Tan Shurong Carol, Lu Jinhua

57 Structural Refolding of Hepatitis B Virus X Protein (HBx) . . . 75Oh 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 . . 76Si Kee Tan, Zhen Hua Lin, Cheng Wei Chang, Kern Rei Chng, EuLeong Yong, Edwin Cheung

59 Understanding the Regulatory Network of Androgen Receptorand TMPRSS2-ERG Fusion Protein in Prostate Cancer Progression 77

Chng Kern Rei, Tan Si Kee, Chang Cheng Wei, Yang Chong, HongShuzhen, Edwin Cheung

60 Bcl-2 Modulates Resveratrol-induced ROS Production by Regu-lating Mitochondrial Respiration in Tumor Cells . . . . . . . . . 78Ivan Cherh Chiet Low, Shazib Pervaiz

61 A Novel Role for RUNX3 in the Regulation of IL23A . . . . . . . 79Yit Teng Hor, Dominic Voon Chih Cheng, Jason Koo Kin Wai, HuajingWang, Yoshiaki Ito

62 Characterization of the Role of E7 in Transcriptional Regulationof Mitotic Genes . . . . . . . . . . . . . . . . . . . . . . . . . . . 80Pang Chai Ling, Teissier Sebastien, Thierry Francoise

63 Identification of Recurrent Regions of Copy Number VariantsAcross Multiple Individuals . . . . . . . . . . . . . . . . . . . . . 81Teo Shu Mei, Agus Salim, Yudi Pawitan

64 Dengue Virus Neutralization in Human Monocytes . . . . . . . . 82Chan 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 ofEnterovirus 71 in a Neonate Mouse Model . . . . . . . . . . . . . 83Khong Wei Xin, Damian G. W. Foo, Tan Eng Lee, Sylvie Alonso

66 Role of Rac1 in Regulating Bcl-2 Mediated Chemoresistance andPro-oxidant State in Tumour Cells . . . . . . . . . . . . . . . . . 84Kang 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 . . . . . . . . . . . . . . . . . . . 85Zhou 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 . . . . . . . . . . . . . . . . 88Wong Swee Liang

69 Structure and Mechanical Properties Study of Bombyx Mori Silk-worm Silk Fibrils by Atomic Force Microscope and X-ray Diffraction 89Deng Qinqiu

70 Nanoparticles Fractionation using Aligned Carbon Nanotube Array 90Xiaodai Lim, Hairuo Xu, Yi Hui Nicole Chew, Yi Hui Phua, EdbertJarvis 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 . . . . . . . . . . . . . . . . . . . . 91Yip Ai Kia, Chiam Keng Hwee, Paul Matsudaira

72 Dynamic-based Structure Measures on Complex Networks . . . . 92Zhu Guimei, Li Baowen

Welcome to the 3rd NGS student symposium

Li Baowen

The NGS symposium is a great platform for NGS students to exchange theirresearch results and novel ideas with fellows from other disciplines, and withsenior scientists. We are living in an era of many cutting edge technologies andscientific discoveries, borne from interactions among scientists and engineersfrom different disciplines and backgrounds. Much of the most exciting researchlies in the intersecting areas of different fields.

Distinguished scientists and engineers are very often valuable role models andresources of inspiration for young researchers. This year, we are very pleasedto 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 willdefinitely give you encouragement and motivation to cross boundaries to ex-plore new territories. Prof. Zee is a theoretical physicist trained in Princeton(B.Sc) and Harvard (Ph. D.). His research spans high energy physics, field the-ory, 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 booksincluding “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 tohave a proof that it is.” He is a classical example showing that you cannotonly excel in your primary research field, but also express your passion in otherbeloved fields.

Prof. Ding Jeak Ling, a Provost Chair Professor at Department of BiologicalScience, NUS, has been working in innate immunity and host-pathogen surveil-lance strategies for many years. Because of her outstanding research, she hasbeen awarded numerous awards including 1995 NSTB Award for outstandingresearch, 2000 Far Eastern Economic Review Award for Outstanding Research,2001 and 2008 NUS Outstanding Researcher Award. All of these and her manyactivities in NGS and NUS have made her an excellent mentor.

Complementing these keynote talks, I am sure that you will equally enjoyall the students’ talks from the diverse disciplines presented in this symposium.

Li BaowenProfessor of PhysicsExecutive Director

NUS Graduate for Integrative Science and Engineering

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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 broadappreciation of the subject. The talk will draw upon historical developments aswell as from my personal experience.

Curriculum VitaeAnthony Zee, 徐一鸿 , (born in Kunming in China) is a Chinese Americanphysicist, writer, and currently a professor at the Kavli Institute for Theoret-ical Physics and the physics department of the University of California, SantaBarbara. Zee obtained his Ph. D. from Harvard in 1970. During 1970-72 and1977-78, he was at the Institute for Advanced Study. From 1973 to 1978, hewas 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 Zeehas authored or co-authored more than 200 scientific publications and severalbooks. He has written on particle physics, condensed matter physics, anomaliesin physics, random matrix theory, superconductivity, the quantum Hall effect,and other topics in theoretical physics and evolutionary biology, as well as theirvarious interrelations. His scientific publications have been cited more than10,000 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 ofhis teaching is his text Quantum Field Theory in a Nutshell. He is also theauthor of several books for general readers about physics and Chinese culture.http://en.wikipedia.org/wiki/Anthony Zeehttp://www.kitp.ucsb.edu/˜zee/index.php

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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 roadsleading to-and-from research. Do we fashion our research according to ourhearts’ desire, to where the need is, or to where the funding source is focusingon? 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. Sometimesthe compass was driven by the research funding focus, but mostly the pathspursued have been based on my own bearing of fundamental research interest,albeit keeping alert to translational research, to capture any potential biotech-nological gains. I will share my experiences on intellectual property protectionand commercialization of research products, as well as publishing and not per-ishing. Often, we cannot predict the outcome, but a flexible, imaginative andaccommodating mind can be most rewarding........

Curriculum VitaeDing Jeak Ling is a Professor at the Department of Biological Sciences as well asthe Provost Chair Professor of National University of Singapore. Her researchinterest is the frontline immune defense mechanisms during acute phase infec-tion. Beside academic research, she is also a successful technopreneur, with twopatents which have been commercialized by Lonza Inc and BioDTech Inc. Shehas also been awarded the Far Eastern Economic Review Award for outstandingresearch.

Position Held1982-84 Postdoc. Res. Fellow, MRC Clinical Res. Centre, London, UK.1985-88 Lecturer, Dept. of Zoology, NUS1989-94 Senior Lecturer, Dept. of Zoology, NUS1995-2001 Assoc. Prof., Dept. of Biological Sciences, NUS2001- Professor, Dept. of Biological Sciences, NUS2009- Provost Chair Professor, NUS

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

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timicrobials and anti-inflammatory therapeutics.

Patents & Commercialisation

• Ding JL and Ho B (1998, 1999, 2001, 2002) – Cloning and expression ofhorseshoe crab Factor C for detection, removal of endotoxin & endotoxintherapeutics (US Patents); PyroGene commercialised by Lonza Inc.; LPS-binding Sushi peptides for depyrogenation commercialised to BioDTechInc., 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 re-combinant proteins (US Patent granted).

Recent Administrative positions2005-2007 Member, UPTC2007-2010 Dy. Chair, University Research Council Grant Committee

(Biomedical Engnr. Life Sci.)2006-2010 NUS-YIA (Young Investigator Award) Panel member2007-2009 Member, NGS “Senior Advisory Committee on Graduate Education” (SAGE)2008- Member & Ag Chair, FPTC2010- Chair, NGS Snr. Advisory Committee for Graduate Education (SAGE)

Member, NGS EXCO2010-2012 Member, Singapore Medical Council’s Complaints & Disciplinary Panel

Selected Awards1995 NSTB award for outstanding research in genetic engineering2000 Far Eastern Economic Review Award for outstanding research2001 NUS Outstanding Researcher Award2008 NUS Outstanding Researcher Award2009 Provost Term Chair Professorship

Oral Presentations

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PRESENTATION 1

A Universal Relation between Heat Conductionand Diffusion

Liu Sha1, Li Baowen1

1Center for Computational Science and Engeering, Department of Physics

We rigorously prove a useful equality relating the heat current autocorrelationfunction and the mean square displacement of the energy diffusion. From thisequality, we are able to recover the existing theories for normal diffusion andnormal heat conduction. Moreover, we are also able to obtain a connectionbetween anomalous diffusion and anomalous heat conduction. Our results areapplicable to all isotropic systems with any dimension.

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PRESENTATION 2

Automated Aesthetic Enhancement of Videos

Xiang Yangyang1, Mohan Kankanhalli21NUS Graduate School for Integrative Sciences and Engineering

2School of Computing

We present a content based single-shot video editing scheme. We follow theclassic 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 basedon film theories. The system segments interesting sub-shots and ordinary sub-shots within the single video clip. Different sub-shots are projected to differentduration to maximize the video interest. The output video is rendered accord-ing to adjusted projection duration. Within this framework, we transform thescreen rhythm and camera motion of a given single video shot. Motion inter-ests of frames are re-distributed in projection duration modification and certainspecial projection patterns are introduced to enhance the aesthetic interest oforiginal video. The user study shows that our scheme is very effective.

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PRESENTATION 3

Development of an Health Monitoring Systemfor 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 systemfor the elderly at home. The system integrates ZigBee mesh network, cellu-lar network, ubiquitous and mobile computing, hardware miniaturization andvarious sensor technologies. The centerpieces are wearable devices that are ca-pable of detecting accidental falls, monitoring heart rate, tracking locations,etc. The wearable devices are modular so that certain sensors can be added ina plug-and-play fashion. Wearable devices communicate with the Base Stationcentered at home via ZigBee mesh network. The base station is integrated witha GSM module. Vital signs and health status sent from wearable devices willbe forwarded to caregivers’ mobile phones in real time via SMS. Meanwhile,caregivers are able to query status and even initiate basic diagnosis via SMS incase of emergency. The paper will focus on hardware and software architecturesas well as low power design for data acquisition and signal processing in wirelesssensors.

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PRESENTATION 4

Building 3D Tissue Structures WithPolyelectrolyte Fibers

Toh Kah Chin Jerry1,2, Leong Meng Fatt1, Andrew Wan1,Jackie Y. Ying1

1Institute of Bioengineering and Nanotechnology2NUS Graduate School for Integrative Sciences and Engineering

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

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PRESENTATION 5

Linc-ing Neurogenesis – Long Non-coding RNAsDetermine 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 ofthe 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 developingnervous system in a spatially- and temporally-regulated manner, indicating thatlincRNAs may play a part in neural development. In order to study the rolesof lincRNAs in midbrain neurogenesis, we developed a two-step differentiationscheme in which a pure population of neural progenitors (NPCs) can first bederived from human embryonic stem cells (hESCs). In the second step, NPCswere 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 theundifferentiated hESCs. To investigate if these lincRNAs are functional, knock-down of some of these transcripts were performed in a human neural stem cellline, and their ability to differentiate into neurons was assayed. The silencing ofthree lincRNAs assayed resulted in an inhibition of neurogenesis, indicating thatthese lincRNAs are required for the differentiation of neurons. Using in-vitrotranscribed biotinylated lincRNAs, we sought to determine the mechanisms ofneuronal gene activation brought about by these neural-specific lincRNAs.

10

PRESENTATION 6

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

Zhengkui Wang1, Yue Wang1, Kian-Lee Tan2, Limsoon Wong2,Divyakant Agrawal3

1NUS Graduate School for Integrative Sciences and Engineering2School of Computing

3Department of Computer Science, University of California, Santa Barbara, USA

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

11

Poster Presentations:Biology

13

POSTER 1

CD155 Expression by TLR Agonists onAntigen-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 constitutivelyexpressed on most immune cells. It is expressed at low levels in healthy tissueand is often up-regulated in tumor cells. Binding of CD155 to DNAM-1 inducesNK cell and CD8+ T cell-mediated cytotoxicity and cytokine secretion. Apartfrom its role as an immune cell activating ligand, CD155 serves as an adhesionmolecule and also mediates the migration of leukocytes through blood vessels.In addition interaction of CD155 with TIGIT can also lead to the suppressionof immune system and induction of tolerance. Although the functions of CD155have been well characterised, the mechanisms inducing CD155 expression areyet to be elucidated. To address this question we looked at danger signalssuch as Toll like receptor activation. Here we show that CD155 is induced byToll Like Receptor (TLR) stimulation on professional antigen presenting cells.TLR mediated up-regulation of CD155 is MyD88 and TRIF dependent. Inaddition our data show that NF-ØB and IRF family members are involved inregulating the induction of CD155 expression in response to TLRs. Overallthe data indicates that CD155 serves as a “danger signal” sensor alerting theimmune system to the presence of diseased cells.

14

POSTER 2

Macromolecular Crowding & Stem CellDifferentiation

Rafi Rashid1,2, Michael Raghunath3,4,5, Thorsten Wohland2,6

1NUS Graduate School for Integrative Sciences and Engineering2NUS Centre for Bioimaging Sciences

3Department of Biochemistry, Yong Loo Lin School of Medicine4Division of Bioengineering

5NUS Tissue Engineering Programme6Department of Chemistry

Macromolecular crowding (MMC) is a biophysical tool which has been usedextensively to enhance chemical reactions and biological processes by means ofthe excluded volume effect (EVE). Macromolecular crowding is known to bean important feature of cells as it governs all biochemical reactions. The cyto-plasm and organelles, such as the mitochondria and nucleus, are crowded withsmall solutes, soluble macromolecules, cytoskeletal proteins and membranes.Cell membranes are also crowded with lipid and protein molecules. One biolog-ical application of crowders is the enhancement of the differentiation of humanmesenchymal stem cells (hMSCs) into the adipogenic lineage. We have postu-lated that these crowders bring about biological effects by changing diffusionrates on the cellular plasma membrane. In order to fully understand the effectsof crowders on cells, we have measured the diffusion of fluorophores of varioussizes in solutions of several crowder species over a wide concentration range byfluorescence correlation spectroscopy (FCS). We have also performed measure-ments on supported lipid bilayers and cellular membranes in the presence ofcrowder molecules using FCS. The data presented here suggest that crowdingagents such as Ficoll 70 kDa, Ficoll 400 kDa and dextran 70 kDa can affect dif-fusion via changes in viscosity, but it is still not clear whether or not excludedvolume effects are present as well. The confocal-FCS measurements do notshow that the Fc70/Fc400 mixture (which is used to potentiate differentiationof stem cells) is having any direct effect on membrane dynamics. However, inthe cellular context, it is possible that crowders are producing effects via othermechanisms. We also show here that, contrary to popular belief, crowders arenot inert and are capable of entering the cytoplasm of cells. New experimentsare needed to determine any possible connection between crowder uptake (orexcluded volume) and the enhanced differentiation of stem cells.

15

POSTER 3

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

Joanne Toh1,2, Murni Tio2, Gerald Udolph2

1NUS Graduate School for Integrative Sciences and Engineering2Institute of Medical Biology, Agency for Science Technology and Research

The fruit fly Drosophila provides an ideal model system to study the functionof genes that control neurogenesis, allowing us to understand the mechanismsthat generate and pattern the nervous system. Homeodomain-containing tran-scription factors are known to act in combination to specify different neuronalidentities or neuronal subtypes. Here, we characterize a paired-type homeoboxgene, D-Ptx1, which is a Drosophila homolog of the Pitx family. D-Ptx1 wasfirst observed to be expressed in segmentally repeated patterns in embryoniccentral nervous system and in a subset of muscles. D-Ptx1 expression can alsobe found in the larval brain lobes and the ventral nerve cord (vNC) where itis expressed in some neurons. Functional characterization of D-Ptx1 mutantsrevealed defects in the axonal projections in the vNC and the peripheral nervoussystem (PNS). We also observed gain or loss of neurons, indicating that D-Ptx1might play roles in neuronal cell fate specification. Knockdown of D-Ptx1 usingsiRNA technology demonstrated that D-Ptx1 is required during embryonic andlarval neurogenesis particularly in axonal pathfinding as well as during myoge-nesis. Interestingly, Tyrosine Hydroxylase (TH) expression was partially lostin the larval vNC, suggesting that D-Ptx1 may be needed for larval dopamin-ergic neurons. Over expression studies of D-Ptx1 revealed defects in the PNSas well as in the vNC. Taken together, we hypothesize that D-Ptx1 is requiredfor some aspects of neuronal differentiation. Further studies are required to un-derstand the molecular mechanisms of D-Ptx1 function during nervous systemdevelopment.

16

POSTER 4

Integrating Multiple Signals in ImmuneModulation

Tan Suet Ting Rebecca1,2, Ding Jeak Ling1,2

1Department of Biological Sciences2NUS Graduate School for Integrative Sciences and Engineering

Early research on TLR-mediated signaling has focused on the effects of sin-gle ligands and their receptors. However, a single pathogen contains multiplepathogen-associated molecular patterns (PAMPs) and is likely to engage multi-ple pathways simultaneously. Innate immune cells employ a range of receptorsto detect specific PAMPs (e.g. TLR, NLR, RLR), integrating these individualsignals in order to mount an appropriate response. Here, we have found thatcertain combinations of TLR ligands cause a much greater response than whenthe ligands are administered singly, a phenomenon described as synergy. Inparticular, 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 asIL-6 and IL-12p40. Other than the combination of PAMPs, synergy is stronglyinfluenced by the timing of stimulation. Two main classes of cytokine behaviourhave been observed, showing optimal synergy either upon simultaneous stimu-lation or when the second stimulation is administered 8 h after the first. Takentogether, these data show that the innate immune system discriminates betweendifferent combinations of PAMPs and the response mounted is highly contextdependent.

17

POSTER 5

Characterization and Long-term HomingPotential of Pregnancy Associated Progenitor

Cells (PAPCs) in a Murine Model ofFetomaternal Microchimerism

Yeo Ailing1

1Institute of Medical Biology

Bidirectional cell trafficking between fetus and mother during pregnancy is awell-established phenomenon observed in placental vertebrates. Although stud-ies have shown that transmigratory fetal cells, also termed pregnancy-associatedprogenitor cells (PAPCs), can integrate into multiple maternal organs, the in-tegration, and differentiation of PAPCs in organs such as the brain has notbeen extensively studied. Particularly, there is a lack of data on the long termpresence as well as the temporal dynamics of PAPCs in healthy mothers. To de-termine the long term engraftment potential of PAPCs in healthy mothers, thepresence of GFP+ PAPCs within a panel of maternal organs was studied. Us-ing qPCR and FACS, PAPCs were observed in the maternal circulation as earlyas E12.5 but numbers decreased immediately after delivery. Despite the lackof cells in the peripheral blood postpartum, PAPCs could be found in multiplematernal organs up to 7 months post partum. This suggested long-term homingcapabilities of PAPCs which raised the question whether PAPCs were able tointegrate and differentiate into organ-specific cell types. To answer this ques-tion, the differentiation capability of PAPCs in the maternal brain was studiedusing Thy1-YFP mouse model. PAPCs were found to adopt neuronal cell fatesin multiple brain regions. It was demonstrated that PAPCs underwent neuronalmaturation in the hippocampus and the results also indicated that mechanismsof neuronal maturation of PAPCs could be similar to that described in adultneurogenesis. 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 CellLines 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 celldysfunction or death in diabetic patients, comparative genome-wide gene ex-pression studies of recently derived mouse insulin-producing cell lines and theirprogenitor cell lines were performed using microarray technology. Differen-tially expressed genes were functionally clustered to identify important bio-chemical pathways in these insulin-producing cell lines. Biochemical or cel-lular assays were then performed to assess the relevance of these pathwaysto the biology of these cells. 185 genes were highly expressed in the insulin-producing cell lines and computational analysis predicted pentose phosphatepathway (PPP), clathrin-mediated endocytosis and the peroxisome proliferator-activated receptor (PPAR) signaling pathway as important pathways in thesecell lines. Insulin-producing ERoSHK cells were more resistant to hydrogen per-oxide (H2O2)-induced oxidative stress. Inhibition of PPP by dehydroepiandros-terone (DHEA) and 6-aminonicotinamide (6-AN) abrogated this H2O2 resis-tance with a concomitant decrease in PPP activity as measured by MTT as-say. Clathrin-mediated endocytosis which is essential in maintaining membranehomeostasis in secreting cells was upregulated by glucose in ERoSHK but not intheir progenitor ERoSH cells. Its inhibition by chlorpromazine at high glucoseconcentration was toxic to the cells. Troglitazone, a PPAR agonist, upregulatedexpression of Ins1 and Ins2, but not Glut2. Gene expression analysis has iden-tified PPP, clathrin-mediated endocytosis and the PPAR signaling pathway asthe major delineating pathways in these insulin-producing cell lines and theirbiological relevance was confirmed by biochemical and cellular assays.

19

POSTER 7

Identification and Characterization of theVertebrate Motile Ciliome

Deepak Babu1,2


Cilia and flagella are hair-like organelles with diverse roles in animal develop-ment, physiological homeostasis, and human health. While the function of theseorganelles is currently being investigated, little is known about the genes andgene networks underlying ciliogenesis. Previous work, from our group and oth-ers, has shown a master regulatory role for the winged-helix transcription factorFoxj1 in motile ciliogenesis. We have utilized this information to carry out agenome-wide microarray-based screen to identify the transcriptional targets ofFoxj1. This is an endeavor to define and characterize all genes which have rolesin ciliogenesis, ciliary structure and function. 548 genes with mammalian or-thologs were found to be up-regulated in response to over-expression of Foxj1in zebrafish embryos. We further validated the array results by performing RT-PCR on a random subset of 55 genes. To characterize novel genes from thecollection, we are carrying out systematic gene knock-down using morpholinooligonucleotides, and assaying for perturbations in ciliary architecture as well asexamining developmental and physiological read-outs of defective cilia such asalterations in left-right asymmetry. In addition, using GFP-tagged versions ofthe proteins encoded by the genes, we are performing localization studies withrespect to the ciliary apparatus. Our findings thus far indicate that the screenhas successfully identified a set of novel genes required for ciliary developmentand function. Based on our results in the zebrafish, we believe that these novelciliary 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 Research2NUS Graduate School for Integrative Sciences and Engineering

The RhoGTPases are critical proteins involved in signal transduction pathwaysthat reorganize the actin cytoskeleton. The many effectors of Rho GTPasestransduce these signals to the cytoskeleton by recruitment of adaptors, actinbinding 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 referredto as INCA, which plays a role in neural crest morphogenesis. INCA has noknown domains based on homology searches other than a central 38 residueInca-box’ that is well conserved among vertebrate Inca proteins. Interestingly,we identified a gene product related to Inca that can also bind Pak4. On thisbasis, 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 withfull-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 possibleamong Maya, Pak4 and another Maya-interacting protein. The localizationof Maya is affected by co-transfection with either of its interacting proteins,of which one is able to influence actin reorganization. Therefore, I propose amodel in which Pak4 could also be involved in the regulation of actin assemblythrough this tri-complex association, in which Maya acts as a molecular bridge.

21

POSTER 9

A Novel Anticoagulant from Amblyommavariegatum (Tropical Bont Tick)

Angelina Tan1, Maria Kazimirova2, RM Kini1,3

1NUS Graduate School for Integrative Sciences and Engineering2Institute of Zoology, Slovak Academy of Sciences

3Department of Biological Sciences

The salivary glands of haematophagaous insects are a rich source of moleculeswith anti-inflammatory, anti-haemostatic and immune-modulatory functions.They act to counter the host defence system during feeding of blood of animalsby the insects, with the salivary gland activity and saliva secretion increasedthroughout this period of time. Our interest lies in the identification and char-acterization of novel anticoagulants from the saliva of Amblyomma variegatum,commonly known as the tropical bont tick. Preliminary screening of salivarygland extracts from this tick has revealed the presence of anticoagulants, par-ticularly, an inhibitor of factor Xa of the coagulation cascade. In an attemptto characterize this factor Xa inhibitor, we first sought to purify and isolate itthrough liquid chromatography. Anti-factor Xa activity was then detected byenzyme inhibition assays with a chromogenic substrate. Sequence and structuredetermination for functional studies is currently in progress. The aim of thisproject is to characterize this factor Xa inhibitor and study its structure-functionrelationship with factor Xa, in prospect of future development of potentiallytherapeutic drugs.

22

POSTER 10

CENTDIST: Discovery of Co-associated Factorsby Motif Distribution

Chang Cheng Wei1, Zhang Zhizhuo2, Goh Wan Ling1, CheungChong Wing1, Sung Wing King5

1Genome Institute of Singapore, Agency for Science Technology and Research2School of Computing

Transcription factors (TFs) do not function alone but work together with otherTFs (called co-associated factors or co-TFs) in specific combinations to preciselycontrol the transcription of target genes. Identifying the entire complement ofco-TFs of a given TF will be an important step in understanding the transcrip-tional regulation mechanism. Existing methods predict co-TFs by counting themotif sites around ChIP-seq peaks. Their accuracy depends on whether the usercan correctly supply the background model, the enrichment window size, andthe PWM cutoff score for each motif.

We have developed a novel application called CENTDIST, which does notrequire the input of any user-specific parameters. Instead CENTDIST usesinformation from the imbalanced distribution of binding sites for identifyingco-TFs (http://compbio.ddns.comp.nus.edu.sg/˜chipseq/webseqtools/). Usingthis new statistical model, we correctly predicted all known co-TFs of AR inthe 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 forTFs in mouse embryonic stem cells and obtained results with similar success.Taken together, CENTDIST, a web-based program based on the imbalanceddistribution of co-TF binding sites provides a user-friendly, parameter-less, andpowerful predictive tool for understanding the co-regulation mechanism of TFs.

23

POSTER 11

Structural and Functional Study of a Spider SilkProtein-AcSp1

Wang Shujing1,2

1NUS Graduate School for Integrative Sciences and EngineeringNGS2Department of Biological Sciences

Spider silk is high performance protein-based fibre, which has attracted humaninterest for thousands of years. AcSp1 protein, which can form aciniform silk, isreported to assemble into the small diameter fibers of egg case sacs and wrappingsilks and can also construct web decorations and build sperm webs. Aciniformsilk has been reported to be of the highest toughness among all the spider silksstudied and current studies show that soluble domains of AcSp1 contain mainlyα-helices and random coils, while conformation and orientation study of naturalsilk indicates it contains both α-helices and β-sheets. To further understandthe molecular mechanism of spider silk formation and explain the specificity ofAcSp1, the tertiary structure of each domain and the domain-domain interactionstudies come to be the first choice using recombinant AcSp1 proteins. Our studystarts from the most elementary soluble structure determination of differentdomains of AcSp1 by NMR, and, based on which, we study the interaction ofdifferent domains using different domain construct, aiming to provide hints onthe AcSp1 silk-formation mechanism elucidation. Also, AcSp1 silk miniaturestudy in vitro is of great importance for large scale artificial silk-like materialproduction.

24

POSTER 12

Natural Variant Forms of C1q

Leong Jing Yao1

1Microbiology Department

C1q is a macromolecular complex composed of 18 polypeptide chains, composedof 3 fundamental chains (C1q A, B and C). C1q is implicated in several diseasessuch as Systemic Lupus Erthymatosus (SLE), artherosclerosis, Alzheimer dis-ease, Prion disease and Antibody Dependent Enhancement (ADE) phenomenonin the flavivirus family (e.g Dengue, West Nile virus). It is interesting to notethat in many of the disease implicated, C1q plays a protective role in delayingthe onset in the early phase of the disease, however in the later phase of thedisease, it plays a pathogenic role. Essentially, C1q plays a pathogenic role byactivating the classical pathway of complement activation, resulting in the cre-ation of an inflammatory environment (e.g recruiting immune cells), and on thereverse side of the coin, plays a protective role by enhancing the clearance ofcellular debris (e.g apoptotic cells). Investigation into the secreted forms of C1qfrom important immune regulatory/phagocytic cells such as dendritic cells andmacrophages in this project, revealed that a different form of C1q exists (termedas Low molecular weight or LMW). This LMW C1q was shown to exhibit a lowerability to active the classical pathway of complement activation and was ableto enhance clearance of apoptotic cells. This seems to indicate that the dualnature (protective/pathogenic) of C1q could be better regulated by secretingthe different forms of C1q. A methodology of purifying the LMW C1q fromhuman serum was devised, and the protein now is under intense investigationfor its functional properties.

25

POSTER 13

Development of Living Color Transgenic Medakafor Biomonitoring Aquatic Contamination

Ng Hwee Boon Grace1,2


With the advent of GFP reporter gene, it is feasible to apply the living colortransgenic fish in monitoring water contamination. We report the genera-tion of two biomonitoring transgenic medaka lines using a stress-inducible pro-moter, hsp70 and xenobiotic inducible promoter, cyp1a1 with the designation ofTg(hsp70:gfp) and Tg(cyp1a1:gfp) respectively. The transgenic lines were gen-erated with the aid of maize Ac/Ds transposon system. Most founders screenedwere positive for germline transmission, thus indicating a high efficiency of theAc/Ds system to aid transgene integration. Induction of GFP expression inTg(hsp70:gfp) by heat shock treatment at 37◦C and heavy metals such as mer-cury, copper and cadmium demonstrate the inducibility of hsp70 promoter.Interestingly, specific heavy metals invoke certain GFP expression patterns invarious organs of the embryos. Thus the newly developed transgenic line maybe useful for monitoring stresses caused by heavy metals and may establish apattern database to specify types of heavy metal insults. As for Tg(cyp1a1:gfp),GFP expression was observed in liver when treated with xenobiotic compoundssuch as Benzo[α]pyrene(BAP) and it was also observed in other organs such askidney 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 responsivenessand 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 andtoxins into their environment or directly into their hosts. So far 7 of themhave been discovered. Edwardsiella tarda is a gram nagetive bacterium whichutilizes both Type III and Type VI secretion systems to infect fish. EvpP is aunique effector from its Type VI Secretion System (T6SS). It has no homologueacross different species that possess a T6SS. Previous study shows that knockingout EvpP hinders bacterial secretion of E. tarda. Yet so far, the structure aswell as the exact function of EvpP still remains unknown. EvpP is a 20kDprotein secreted together by T6SS with EvpC and EvpI. Current experimentsshow that EvpP and EvpC may have binding interaction. EvpP on its own isnot very stable and tends to degrade to a 10kD piece over time. However it isresistant to common protease digestion. Only trypsin cuts EvpP and gives riseto a shorter piece also around 10kD. Interestingly N-terminal sequencing showsthat the trypsin digested EvpP agrees with the self-degraded one. We are nowtrying to mass produce the shorter piece and solve its structure since this seemsto be the rigid part of the whole protein. We will also investigate the functionof EvpP after it gets secreted: whether it enters host cell or it stays just in theenvironment.

27

POSTER 15

Novel Approaches for the Identification of ViralEpitopes Associated with Asian HLA Employing

Conditional Ligands

Cynthia Xin Lei Chang1,2, Ming Yan Or1, Kai Yee Toh1, AnthonyT 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 ofMedicine

2NUS Graduate School for Integrative Sciences and Engineering3Singapore Institute for Clinical Sciences, Agency for Science Technology and

Research4Collaborative Anti-Viral Research Group, Institute of Molecular and Cell Biology,

Agency for Science, Technology and Research

The development of immunotherapies relies on valuable information regardinghow the adaptive immune system recognizes and responds to infections. Specif-ically, epitopes presented by an appropriate class I Major HistocompatibilityComplex (MHC) can induce a response from CD8+ T cells following recog-nition by its corresponding T cell receptor (TCR). The specificity of the im-mune response is dictated by the source of antigen, making the identificationof pathogen-specific epitopes essential. The constellation of HLA restrictionelements for each individual is a second determinant in antigen presentation,since genetic polymorphisms in the HLA influences peptide affinity for the geneproduct. For Asian variants of Human Leukocyte Antigen (HLA) little informa-tion on epitope specificity is currently available. CD8+ T cell epitope discoverycan be achieved using recently developed high-throughput MHC enzyme-linkedimmunosorbent assay (ELISA) and MHC tetramer staining protocols. We there-fore synthesized recombinant HLA class I molecules of allelic variants commonin Asian populations, for example HLA-B*5801 and HLA-B*4001, complexedwith ultra-violet (UV) light-sensitive conditional ligands. After UV irradiation,the cleaved ligand can be replaced by a peptide of choice thereby producinga novel peptide-MHC (pMHC) complex. The peptide exchange efficiency canbe determined using an ELISA that compares the ability of various peptidesto rescue the MHC after UV-mediated cleavage of conditional ligand. Further-more, the peptide exchange technology allows for high-throughput production ofMHC tetramer libraries for epitope discovery. We will present data that appro-priate MHC tetramer staining for the direct identification of in vitro expandedantigen-specific CD8+ T cells is achievable. Employing these methods, we showthe successful determination of HLA restriction and fine specificity of epitopesfrom Severe Acute Respiratory Symptoms (SARS) and Hepatitis B Virus (HBV)that are associated with Asian HLA variants. Acknowledgment: This work wassupported by the NRF Research Fellowship (NRF2007 NRF-RF001-226)

28

POSTER 16

Novel Antibodies against Virulence Factors ofthe Type VI Secretion System in Burkholderia

pseudomallei

Lim Yan Ting1,2, Paul A MacAry1, Gan Yunn Hwen3

1Department of Microbiology, Immunology Program2NUS Graduate School for Integrative Sciences and Engineering

3Department of Biochemistry, Immunology Program

The type VI secretion system (TSSS) is the latest addition to the previousfive categories of Gram-negative protein secretion systems. Evidence of its roleas a potential virulence factor in several Gram-negative pathogens has beenhighlighted, and this system is also present in Burkholderia pseudomallei, thecausative agent of meliodosis. Hence, there are practical reasons for generatingimmunological reagents for studying the system in depth, which could aid in thedevelopment of new therapies and/or diagnostics. Our lab has thus currentlygenerated novel antibodies against interesting components of the B. pseudoma-llei TSSS, which have enabled improved understanding of the basic biology ofthe pathogen.

29

POSTER 17

Altered Cellular Iron Metabolism DuringSenescence in IMR-90 Fibroblasts

Hendry S. Cahaya2,3,4,5, David W. Killilea4, Sebastian Schaffer5,Bruce Ames1,4, Barry Halliwell5

1Department of Biochemistry, UC Berkeley2Department of Molecular & Cell Biology, UC Berkeley

3NUS Graduate School for Integrative Sciences and Engineering4Center for Nutrition and Metabolism, Childrens Hospital Oakland Research

Institute5Department 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, theregulation of iron homeostasis was investigated in primary cultures of humanfibroblast (IMR-90) as a model of cellular senescence. Previously, total intracel-lular iron, as determined by inductively-coupled plasma spectrometry, increasedexponentially in IMR-90 as a function of age in culture. Age-related iron ac-cumulation was also found to follow a parallel relationship with the oxidativestate of the cell. Interestingly, modulating intracellular iron levels by chronictreatment of ferrous iron-citrate or iron-chelators had no effect on senescence,suggesting that age-related iron accumulation is a consequence, not a cause ofcellular senescence. Iron uptake is predominantly mediated by transferrin recep-tor (TfR). During high metabolic iron demand, the expression of TfR densityincreases. Despite sufficient iron level, TfR density increased with age as deter-mined by immunocytochemistry and Western blot analysis. The level of ferritinalso increased as with age, despite the normally inverse relationship of TfR andferritin. Moreover, the level of redox active labile iron pool as measured bycalcein fluorometry increased in tandem with cellular senescence. Thus, home-ostatic control of iron could be altered during cellular senescence. One possiblemediator of this change could be attributed from oxidative stress, which canuncouple the activity of the iron response proteins that regulate the expressionof TfR, ferritin and other key regulatory proteins. Age-related oxidative stressmay drive intracellular iron accumulation in human cells and induce cellulardysfunction.

30

POSTER 18

Live Ratiometric Ca2+ Imaging in a ZebrafishModel of Spinal Muscular atrophy

Kelvin See1,2, Christoph Winkler1,2


Spinal Muscular Atrophy (SMA) is a progressive neurodegenerative diseasespecifically affecting lower motor neurons in the spinal cord. Mutations in theubiquitously expressed Survival Motor Neuron (SMN) gene, which encodes aprotein implicated in snRNP assembly, is known as cause of this disease butdetailed molecular mechanisms for the motor neuron specific phenotype are stillunclear. Abnormal synaptic transmission and altered presynaptic Ca2+ levelshave 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 asa non-invasive reporter for motor neuron function. Two novel zebrafish stabletransgenic lines have been established which make use of a FRET based Ca2+

sensor to detect changes in intracellular Ca2+ levels in CaP motor axons andin cells surrounding the CaP axons respectively. In one transgenic line, it wasunexpectedly found that the sensor was expressed in cells surrounding the CaPaxon. 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 inCa2+ influx into these glia cells during synaptic transmission in SMN morphantzebrafish embryos compared to uninjected controls. This suggests that the func-tion of glia around the motor axons in regulating synaptic transmission may beaffected in SMA. These novel transgenic lines may serve as a platform to assessmotor neuron activity or glia excitability in live zebrafish and may be extendedto 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 andResearch

2NUS Graduate School for Integrative Sciences and Engineering3Department of Biochemistry, Yong Loo Lin School of Medicine

The Wnt signalling pathway is commonly dysregulated in colorectal cancer, adisease in which PRL-3 (phosphatase of regenerating liver 3) has been implicatedto play a key role in metastatic progression. In a search for potential PRL-3 reg-ulated proteins in the Wnt pathway, beta-catenin was identified as a candidateregulated protein in A2780 ovarian carcinoma cells. In these cells, stable over-expression of PRL-3 (wild-type or catalytically dead) potently downregulatedbeta-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 ofthis proteosomally-degraded protein. In a search for candidate dysregulatedcomponents of the beta-catenin degradation machinery, Dvl2/3 and Naked1/2were identified to be antagonistically regulated by PRL-3: PRL-3 downregu-lated Dvl2/3, but upregulated Naked1/2. This is an intriguing result, giventhat Dvl has been reported to promote beta-catenin stability, whereas Nakedsequesters Dvl to antagonize this protective effect on beta-catenin, thereby en-hancing its degradation. The significance of beta-catenin downregulation toPRL-3-mediated oncogenesis is being actively studied.

32

POSTER 20

EGF signaling pathway involvement inregulating 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 Research2NUS Graduate School for Integrative Sciences and Engineering

Epidermolysis Bullosa Simplex (EBS) is a human skin blistering disease causedby mutations in the keratin intermediate filament genes KRT5 or KRT14. Ker-atinocytes harboring the severe EBS Dowling-Meara mutation R125P on ker-atin 14 (Rod 1A domain) spontaneously form abnormal keratin aggregates, ofwhich the nature of their formation are poorly understood. To investigate themolecular mechanism underlying the formation of mutant keratins in vivo, im-mortalized keratinocytes were stably transfected with EGFP tagged with eitherK14 wild-type or K14 R125P.Time-lapse imaging showed that EGFP-K14 R125P was localized as aggregatesat the lamellipodial regions of the isogenic pathomimetic keratinocytes. Strik-ingly, these peripheral aggregates were highly dynamic, and were constantlyundergoing assembly and disassembly upon cell migration.Protein extract analysis revealed an elevated level of phosphorylated ERK1/2expression in mutant keratinocytes as compared to wild-type keratinocytes, andindirect immuofluorescence has shown that phosphorylated ERK1/2 co-localizedwith peripheral keratin aggregates of the mutant keratinocytes. MEK1/2 in-hibitor was then used to inhibit ERK1/2 activity, which resulted in fewer mu-tant keratinocytes having aggregates. This observation was further supportedby time-lapse live-cell imaging where ERK1/2 inactivation resulted in slowerkeratin dynamics at the leading edge, which could be ’rescued’ during wash-out.By targeting the upstream signaling pathway, removal of EGF resulted in adrastic reduction in the number of mutant keratinocytes having aggregates,which could be ’rescued’ by re-stimulation with EGF. In this study, we haveidentified that the EGF signaling pathway may be involved in regulating keratindynamics in an EBS disease model.

33

POSTER 21

Cell Cycle Lipidomics

Jing Yan Lim1,2, Markus Wenk1,2

1Department of Biochemistry2NUS Graduate School for Integrative Sciences and Engineering

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

34

Poster Presentations:Chemistry

35

POSTER 22

Synthesis of Heterometallic Cobalt Clusters andTheir Magnetic Properties

Pei Wang1,2, T.S. Andy Hor1,2

1NUS Graduate School for Integrative Sciences and Engineering2Department of Chemistry

Transition metal clusters have been widely explored and shown prominent prop-erties in molecular magnetism and metal catalysis.[1],[2],[3] We have synthesizeda series of cobalt cubane clusters, which exemplify the importance of cobalt oxo-bridged cluster as building blocks for more complicated mono and heterometalliccluster. This has led to the incorporation of alkali metals, alkaline-earth metalsand 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 inthe 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 InducedKeratinocyte Cell Sheet Migration

Loo Eng Kiat, Alvin1,2, Ho Rongjian2, Wong Yee Ting2, BarryHalliwell1,2

1NUS Graduate School for Integrative Sciences and Engineering2Department of Biochemistry

Keratinocyte migration is an important process in wound healing. Numerousstudies have shown that H2O2 can act as a signaling molecule for cell pro-liferation and migration. In this study, we focused on the effect of H2O2 onkeratinocyte cell sheet migration. We found that H2O2 induces a dose depen-dent increase in migration of HaCaT keratinocytes using a scratch wound as-say. While both H2O2 and scratch wounding induce ERK 1/2 and p38 MAPKphosphorylation very strongly in keratinocytes, the phosphorylation inducedby H2O2 was more long-lasting. Inhibition of either ERK 1/2 or p38 MAPKusing pharmacological inhibitors reduced basal cell migration as well as inhib-ited H2O2 induced migration. Both scratch wounding and H2O2 were foundto induce epidermal growth factor receptor (EGFR) phosphorylation. Inhibi-tion of EGFR phosphorylation also inhibited H2O2 induced migration as well asstrongly reducing H2O2 induced ERK 1/2 phosphorylation but not p38 MAPKphosphorylation. This shows that H2O2 induced ERK 1/2 phosphorylation islargely due to the activation of EGFR phosphorylation. While the concentrationof H2O2 used was non-cytotoxic and had a mild proliferative effect, inhibitionof EGFR, ERK 1/2 and p38 phosphorylation sensitizes the cells to H2O2. Thisimplied that activation of these kinases not only induces cell migration but alsoensures that the cell survives the insult.

37

POSTER 24

Targeting the “Turtle” – Metabolic Labelling ofInositol lipids

Shareef Mohideen Ismail1, Sandip Pasari2, Martin Lear2, MarkusWenk1,3

1NUS Graduate School for Integrative Sciences and Engineering2Department 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 inosi-tols, participate in various signalling mechanisms. Higher inositol sphingolipidsand glycosylphosphatidylinositol (GPI) anchors are known to be involved inhost-pathogen interactions and in interactions of the cell with the extracellu-lar environment. Absence of inositol biosynthesis and unavailability from themedia 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 proteindomains (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 inos-itol lipids utilizing metabolic labelling using inositol analogues modified withbioorthogonal groups. Budding yeast, Saccharomyces cerevisiae, was selectedas the model organism to study the effects of the analogues on growth, theirinteractions with the cellular environment and analyze their incorporation intoinositol lipids. Assessment of inositol analogue incorporation was performedthrough mass spectrometry of yeast lipid extracts. Here, we present some ofour results which enhance our understanding of the effects of inositol analogueson the cellular environment.

38

Poster Presentations:Computer Science

39

POSTER 25

Designing Artificial Team-mates for IncreasedAffiliation

Tim Merrit1, Kevin McGee2

1NUS Graduate School for Integrative Sciences and Engineering2Partner Technologies Research Group

An ongoing focus of HCI research has examined how humans treat computerssocially, and in some ways similar to human-human interactions. This is of par-ticular interest to interaction designers because it suggests factors that affectthe way we play games or interact with technology. This research focuses onaffiliation with team-mates in the context of real-time cooperative games, andexamining how affiliation differs depending upon whether the team-mate is anavatar controlled by a computer or another human. Details of preliminary stud-ies suggest that humans respond and affiliate with computer-based team-matesdifferently than with humans, yet there are promising results that suggest thatdesign changes can be made to the computer-based team-mates to encouragean increase in affiliation.

40

POSTER 26

Rereadability in Procedural Hypertext Fiction

Alex Mitchell11NUS Graduate School for Integrative Sciences and Engineering

In hypertext fiction and other forms of interactive storytelling, rereadability andvariability are seen as important differentiating factors between traditional andinteractive stories. There has been extensive work investigating dynamic andadaptive non-fictional hypertext, procedural story generation and procedurally-driven interactive storytelling. There has also been much discussion of reread-ability in literature, and replayability in computer games. However, there hasnot been any research into the specific techniques to support rereadability incomputational, procedurally-driven interactive stories. My thesis research fo-cuses on investigating the nature of rereadability in procedural hypertext fiction,and the ways in which a procedural approach to hypertext fiction can suggestnew forms of rereadability. A deeper understanding of the techniques that canbe used to support the reader’s experience of rereadability can help authors tocreate more compelling interactive stories, and encourage more absorbed, re-flective reading and rereading of interactive texts. To investigate this issue, thefirst step is to identify existing types of rereadability in interactive and non-interactive stories. Following this, different ways to support both existing andnew forms of rereadability will be explored through rapid prototyping of author-ing tools for procedurally-driven interactive hypertext fiction, and the creationof stories with these tools. The resulting stories will be tested with readers toinvestigate their response, and to gain further insight into how these techniquesimpact rereadability. This paper reports the initial findings of the research, andoutlines the remaining challenges.

41

POSTER 27

State Space Reduction for LinearizabilityChecking

Zhang Shaojie1,2

1Department of Computer Science2NUS Graduate School for Integrative Sciences and Engineering

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

42

POSTER 28

Non-negative Matrix Factorization with KLDivergence Criterion Equals Maximum

Likelihood Decomposition

Wang Xuancong1,2, Sim Khe Chai11School 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 ex-traction for speech recognition [1]. In this work, we have shown that NMFusing KL divergence criterion is mathematically equivalent to maximum like-lihood under several normalization constraints by treating each non-negativeobservation feature vector (each column of Y in Y=A*X) as a weighted (byeach column of X) mixture distribution of several random processes (each onewith its own distribution described by columns of the basis matrix A) ratherthan a Euclidean vector. And thus Gaussian Mixture Model is a special caseof NMF by constraining the basis vectors to be Gaussian. We have also donesome experiments showing that NMF is able to capture inherent correlation butis biased by the mean energy in each elements of the observation feature vector.Also the current NMF iterative procedure has the same problem of convergingto local optimum as the Expectation Maximization iterative process. Nonethe-less, by using random initialization, NMF is able to capture an approximatelyoptimal set of basis vectors which can minimize the reconstruction error (mea-sured in terms of KL divergence) of the original data which might be useful fornon-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 Labelingin the Biomedical Domain

Daniel Dahlmeier1, Hwee Tou Ng1,2

1NUS Graduate School for Integrative Sciences and Engineering2Department of Computer Science, School of Computing

Semantic role labeling (SRL) is the natural language processing task of auto-matically identifying those parts of a sentence that contain the answers to simplequestions of the form “-Who did what to whom when and where?”-. SRL isa first step towards enabling computers to understand the meaning of humanlanguage. Thus, it has the potential to greatly benefit information extractionand data mining from free text.

The problem with SRL is that it requires a large number of manually anno-tated examples to learn accurate statistical models. While these resources existfor the newswire domain, there are only few such resources for the biomedicaldomain. 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 needfor new annotated examples.

In our work, we address SRL for the biomedical domain as a domain adap-tation problem. That is, we want to adapt a statistical SRL model learned fromnewswire texts (the source domain) to biomedical texts (the target domain). Weevaluate the performance of three recently proposed domain adaptation algo-rithms for SRL. We are the first to investigate the extent of manual annotationneeded to port an SRL system trained on newswire text to biomedical textby explicitly determining the number of annotated biomedical text examplesneeded to achieve good performance. Our results show that by using domainadaptation the cost for developing an SRL system for the biomedical domaincan be reduced significantly.

44

POSTER 30

SOPRAN: Scalable Online ProactiveRe-optimization in Virtual Machine

Management with Dynamic Workloads

Jian Zhou1, Lei Shi2, Kian-Lee Tan1,2

1NUS Graduate School for Integrative Sciences and Engineering2School of Computing

For a data center to operate effectively (i.e., meeting customers’ Service LevelAgreements (SLAs)) and efficiently (i.e., minimizing resource consumption), thevirtual machines (VMs) must be carefully managed. In particular, as workloadschange, the resource demands of VMs change, which in turn may render theassignment of VMs to physical machines sub-optimal. In this paper we proposeSOPRAN, a Scalable Online Proactive Re-optimizAtioN algorithm, that candynamically adapt the assignment of VMs to physical machines to keep the re-source utilization low without sacrificing the SLAs. SOPRAN characterizes thedynamic workloads in the system using a risk cube model, and approximates theworkload demands with a representative state set. The optimal plan for eachrepresentative state is incrementally generated, forming the switchable plan set.At runtime, a two-phase re-optimization strategy matches the current systemdemand to the closest representative state and actuates the corresponding planin the switchable plan set. At the same time, online monitors profile the actualdemands and refine the risk cube to guarantee the model’s accuracy. We eval-uated SOPRAN against the state-of-the-art IBM MFR algorithm. The resultsshow that, with comparable resource consumptions, SOPRAN can achieve morestable SLA violation rate of no more than 4%, 80% lower migration rate, andsave up to 90% re-optimization overhead.

45

Poster Presentations:Engineering

47

POSTER 31

Mesoporous Poly-Melamine-Formaldehyde forReversible Carbon Dioxide Adsorption

Mei Xuan Tan1,2, Yugen Zhang1, Jackie Y. Ying1,2

1Institute of Bioengineering and Nanotechnology2NUS Graduate School for Integrative Sciences and Engineering

Mesoporous poly-melamine-formaldehyde (PMF) has been developed and syn-thesized 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 1100m2/g, pore width ranging from 6 nm to 23 nm and total pore volume andmicropore volume of up to 3.46 cm3/g and 0.21 cm3/g respectively. It is thefirst time that highly mesoporous melamine-formaldehyde polymer has beensynthesized without the use of inorganic templates or porogens. PMF is foundto have high efficiency in reversible CO2 adsorption. The CO2 adsorption isinstantaneous, reversible and recyclable. The highest CO2 adsorption capacityobtained for PMF is 18.7 wt%. This high capacity of PMF for CO2 adsorptionexceeds that of the organic polymers previously reported in the literature, andis comparable to some zeolites and metal-organic frameworks (MOFs) that havebeen investigated for CO2 adsorption. The CO2 adsorption capacity of PMF iscorrelated with its micropore volume. Due to its robust porosity, high surfacearea and high percentage of amine groups, PMF has many potential applicationsin gas adsorption, gas capture and catalysis, and as a functional material.

48

POSTER 32

Surface-Functionalized andSurface-Functionalizable Poly(vinylidene

fluoride) Graft Copolymer Membranes via ClickChemistry 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 methacry-late) (PGMA) side chains (PVDF-g-P[GMA-(N3)(OH)]) were synthesized viafree radical-initiated graft copolymerization of glycidyl methacrylate (GMA)from ozone-pretreated PVDF backbone (PVDF-g-PGMA), followed by reac-tion of the oxirane rings in the GMA side chains with sodium azide. Alkyne-functionalized poly(N-isopropylacrylamide) (alkynyl-PNIPAM), prepared a pri-ori by atom transfer radical polymerization (ATRP), was used for the clickreaction 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 mem-branes by phase inversion in an aqueous medium. The PVDF-g-P[GMA-(N3)(OH)]microporous membranes with azido-containing surfaces could be further func-tionalized via surface click reaction with alkyne-terminated PNIPAM to obtainthe PVDF-g-P[GMA-click-PNIPAM]surface microporous membranes. The sur-face composition and morphology of the PVDF-g-P[GMA-click-PNIPAM] mem-branes can be adjusted by the temperature of casting medium, while the fluxthrough both types of membranes exhibits thermoresponsive behavior.

49

POSTER 33

Electrospun Nanofibrous Composite forOsteogenic Differentiation of Mesenchymal Stem

Cells

Luong T. H. Nguyen1, Susan Liao2, Seeram Ramakrishna3, CaseyK Chan4

1NUS Graduate School for Integrative Sciences and Engineering2School of Materials Science and Engineering, Nanyang Technological University

3Department of Mechanical Engineering4Orthopedic Surgery, National University Health System

In the body, almost all tissue cells reside in a three-dimensional (3D) environ-ment where cell-cell interactions as well as the presentation of chemical, physicaland mechanical cues in the surrounding fluid and extracellular matrix (ECM)provide the guidance for cellular responses. In nature bone, type I collagen is amajor protein in organic matrix, approximately 95%. Collagen fibrils had a di-ameter range in nanometer scale and orderly deposited by nano-hydroxyapatite(n-HA) mineral crystals. Mimicking these hierarchical structures is a gold strat-egy for the design and fabrication of bone graft materials. We have hypothesizedthat electrospun nanofibrous composites mimicking natural ECM enriched withmesenchymal stem cells (MSCs) will promote bone regeneration. The stud-ies on typical two-dimensional (2D) nanofibrous scaffolds were performed todetermine cellular responses to electrospun nanofibres for the osteogenic differ-entiation of human MSCs (hMSCs). Additionally, biomimetic nanocompositesof poly(L-lactic acid)/Collagen (PLLA+Col) nanofibres deposited with n-HAwere designed, and the results indicated that sustainable supply of Ca/P ionslocally effectively induced the osteogenic differentiation of hMSCs at very earlytime point, even without any osteogenic supplement. Preliminary studies ofusing 3D nanofibrous scaffolds in cell culture were also performed. There was asignificant difference in cell behaviors of hMSCs in the osteogenic differentiationprocess when they were cultured in 3D- and on 2D- electrospun PLLA nanofi-brous scaffolds. The 3D scaffolds considerably enhanced the osteogenic abilityof hMSCs comparing to the 2D scaffolds. As such, biomimetic nanofibrous scaf-folds were shown as a gold strategy for directing osteogenic differentiation ofhMSCs.

50

POSTER 34

Biological Adhesives as Initiator Anchors forSurface-initiated Polymerization in the

Preparation of Multifunctional “Green” Surfaces

Wenjing Yang1, Gary H. Dickinson2, Serena Lay-Ming Teo2, TaoCai1, Koon-Gee Neoh1, En-Tang Kang1

1Department of Chemical and Biomolecular Engineering2Tropical Marine Science Institute

Tethering of functional polymer brushes on the surface is an effective strategy toimpart antifouling and antibacterial properties to the materials, and is of crucialimportance to the effective performance and long service life of biomaterials.[1]In the surface-initiated (SI) polymerization method to prepare well-defined poly-mer brushes, the presence of a stable and durable layer of initiators on the sur-faces is indispensable.[2] Compared to chemical coupling agents that have beenwidely used to immobilize the initiators on various substrates,[3] biomimetic an-chors inspired by biological adhesives are environmentally-friendly, stable andadherent to a variety of substrates.[4] In the present work, barnacle adhesive,a common biological adhesive from marine organism barnacles (Amphibalanusamphitrite), was used as the initiator anchor for SI polymerization to impartmultifunctional properties to stainless steel surfaces. Thus, the amine moietiesof the barnacle adhesive were allowed to react with 2-bromoisobutyryl bromideto provide the alkyl halide initiator for the surface-initiated atom radical transferpolymerization of 2-hydroxyethyl methacrylate (HEMA). The hydroxyl groupsof HEMA polymer brushes were then converted into carboxyl groups for cou-pling of chitosan to impart the stainless steel surface with both antifouling andantibacterial properties. The surface-functionalized stainless steel was very ef-fective in preventing protein adsorption and reducing bacterial adhesion, andexhibited antibacterial efficacy against Escherichia coli.

Key word: Barnacle adhesive, surface-initiated atom transfer radical polymer-ization, antifouling, antibacterial

Reference[1] Xu, F. J.; Neoh, K. G.; Kang, E. T. Bioactive surfaces and biomaterials viaatom transfer radical polymerization. Prog. Polym. Sci. 2009, 34, 719-761.[2] Edmondson, S.; Osborne, V. L.; Huck, W. T. S. Polymer brushes via surfaceinitiated polymerizations. Chem. Soc. Rev. 2004, 33, 14-22.[3] Ma, H.; Wells, M.; Beebe, T. P.; Chilkoti, A. Surface-initiated atom trans-fer radical polymerization of oligo(ethylene glycol) methyl methacrylate from amixed 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 SystemsWith Applications to Autonomous Robotics

Guo Zhaoqin1


In this work, we deal with one of the most challenging control problems - control-ling a class of nonlinear underactuated systems with uncertainties. An underac-tuated unicycle system is used throughout the work to illustrate the effectivenessof 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 anymatched factors, especially the matched uncertainties. As a consequence, asliding manifold is generated, in which the controller design can focus on theunmatched factors only. A unique advantage of the ISMC is its preservationof the same number of actuators in the sliding manifold as the original system.From practice, a linear state-feedback controller, simple and smooth, is foundadequate 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 linearstate feedback for underactuated systems in the presence of unmatched factorssuch as unmatched uncertainties. A main contribution of this part of work isto explore the design issue and effectiveness of the linear controller for the un-deractuated systems. First we reformulate the unmatched factors into severalrepresentative forms, then the linear matrix inequality approach is employed todesign 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 FLCstructure design is model-free and quite user-friendly. However, we encounterthe difficulty in tuning FLC parameters. A linear LQR controller is effective in alocal region of the origin, thus a local linearized system model based parametertuning method which incorporates LQR linear feedback is proposed. Throughcomprehensive simulation-based investigations, the effectiveness of the proposedFLC is validated, and FLC shows superior performance than the LQR. Thedesign procedure indicates that we can easily extend a linear controller to anonlinear one like FLC to achieve more robust performance with respect to taskand plant parameter variations. We can further improve the control performancethrough fine tuning FLC parameters or choosing more generic FLC structurecomponents such as choosing different rule numbers, membership functions,fuzzy inference methods, or choosing different consequent part. Our futurework will focus on totally model free and intelligent controller design.

52

POSTER 36

Analysis and Control of Closed QuantumSystems Based on Real-valued Dynamics

Xue Zhengui1, Lin Hai2, Lee Tong Heng1,2

1NUS Graduate School for Integrative Sciences and Engineering2Department of Electrical and Computer Engineering

Quantum control is concerned with active manipulation of physical and chemi-cal processes on the atomic and molecular scale. Quantum control has attractedgreat attention of researchers because of the unique properties of quantum sys-tems, such as the coherent superposition. Among various applications of quan-tum phenomena, quantum computation is a hot topic due to its really excitingfeatures, e.g., the parallelism computation. To make full use of quantum phe-nomena, it is of great significance to actively manipulate quantum systems.Our work aims to facilitate quantum control design by making use of a de-rived real-valued dynamics, which is equivalent to the Schrodinger equation.Firstly, to obtain the real-valued dynamics, a pure state identication approachis presented. Secondly, the real-valued dynamics is deduced for both two- andthree-level systems. The procedure is also extended to n-level systems. Thirdly,the real-valued dynamics can facilitate the analysis and design of quantum con-trol. It assists one to make full use of classical control theory to implementquantum control. Among various control approaches, a control strategy basedon Lyapunov analysis is considered. Proceeding from the existing Lyapunovcontrol based on the Schrodinger equation, the state transfer problem is studiedwith the assistance of the real-valued dynamics. With the designed control, thegoal state is not necessarily to be an eigenstate of the internal Hamiltonian, andthe state transfer convergence can be achieved without any constraints on theinternal Hamiltonian.

53

POSTER 37

A Real-time Reconstruction Approach forAR-based Applications

Jiang Shuai1,2, Ong Soh Khim1,2, Andrew Y. C. Nee1,2

1Department of Mechanical Engineering2NUS Graduate School for Integrative Sciences and Engineering

Due to the recent development in real-time camera tracking, an increasingamount of research effort has been devoted to vision-based real-time recon-struction, which is also known as the vision-based tracking-and-reconstructingtechnique. With the capability to produce high frame rate virtual models, real-time scene reconstruction has become an integral part for many AR (augmentedreality) based applications. However, as many reported approaches have beenfocused primarily on the accurate modeling of the entire scene, the lack ofmechanism to obtain information on the components of the real scene, e.g., thephysical distribution of the objects in the scene, may have restricted the rangeof applications. In this study, a new reconstruction approach is proposed. Itadopts a point analysis mechanism to identify possible point clusters in the map.As each identified point cluster can be regarded as the virtual representation ofa corresponding object in the real scene, information on the location and theshape of the real objects in the scene can be retrieved in real-time. By employ-ing this approach, after the real objects have been reconstructed based on theclustering results, the retrieved shape and location information could be usedto support advanced operations in many AR-based applications. The potentialof this approach is demonstrated through some experiments.

54

POSTER 38

Image Correlation Spectroscopy as a Tool forMicrorheology of Soft Materials

Nicholas Agung Kurniawan1, Chwee Teck Lim1,2,3, RajRajagopalan1,4,5

1NUS Graduate School for Integrative Sciences and Engineering2Department of Mechanical Engineering

3Department of Bioengineering4Department of Chemical and Biomolecular Engineering

5Chemical and Pharmaceutical Engineering Program, Singapore-MIT Alliance

Image correlation spectroscopy (ICS) is a family of biophysical methods thathas been used to perform spatiotemporal measurements on biological materi-als, especially cells. Some of the early uses of ICS include quantifying spatialdistribution, aggregation state, diffusion coefficient, as well as flow and inter-action of cellular protein molecules. In the present work, we show, in additionto these original applications, how ICS can be used to perform microrheologicalmeasurements (µR) of complex, viscoelastic materials. We test the method,which we call ICS-µR, on Newtonian fluids as well as complex, viscoelastic flu-ids with different viscosities and viscoelastic behaviors. Comparison of ICS-µRresults with reported data from the literature as well as results from conven-tional rheological measurements yields excellent agreement. Furthermore, wedevelop a special technique for extracting mean-squared displacements of tracerparticles in the samples from image correlation data; the technique successfullyreproduces previously published experimental data on a wide range of soft ma-terials displaying a broad range of scaling behaviors. This technique can beapplied to improve the accuracy of other microrheological measurements andcan potentially offer new insights on the power-law behaviors of materials. Thepossibility to combine spatiotemporal assessment and time- and length-scaledependent microrheological measurements from images of fluorescent moleculesmakes ICS-µR a prospective tool in many biophysical applications.

55

POSTER 39

Metabolic Networks Based Approach forUnderstanding Structural Organization

Principles of Essential Genes

Ma Jing1,2

1Centre for Computational Science and Engineering2NUS 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 targetsof study. Identifying essential genes via genome-scale knockout experimentsare resource intensive and are not universally applicable for all species. Herewe propose a metabolic network based approach which aims to understand thestructural organization principles of essential and non-essential genes from Es-cherichia coli. Each gene has a corresponding ’damage list’ where the overallreactions can be affected by gene knockout. Our analysis indicates that essen-tial genes tend to affect reactions catalyzed by other essential genes. This isalso the case for non-essential genes. Besides, two genes with highly correlateddamage lists tend to similarly linked to their respective essentiality, i.e. bothare essential or non-essential. Our results suggest a complementary strategy toknockout experiments to identify essential genes in a genome.

56

POSTER 40

Toxicant-induced Sexual Dimorphic Responsesin Zebra Fish Metabolic System

Zhang Xun1,2

1Centre for Computational Science and Engineering2NUS 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 espe-cially at the in vivo system is a demanding task. Also, sex-dependent toxicityis also an important issue to address. In this study, we used zebra fish asan aquatic vertebrate model to assess toxicant-induced hepatotoxicity. By in-tegrating 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 upto 4 days. This suggests differential metabolic activities of male and femalefish to undergo homeostasis to these toxicants. Intriguingly, the sexual dimor-phic effect makes a more important role in determining gene expression profileeven comparing with the impact of toxicants difference. Using gene enrichmentanalysis, we found lipid metabolism pathway and several relevant pathways be-have oppositely among male and female fish under toxic exposure. Overall, ourstudy emphasizes the significance of sexual dimorphism of metabolic systemin toxic responses. This work can shed light in future endeavors to deciphersex-dependent alteration of metabolism leading to toxicity and pathology.

57

POSTER 41

Remote Maintenance using Augmented RealityTechnology

Zhu Jiang1,2, Andrew Yeh-Ching Nee1,2, Patricia Soh-Khim Ong1,2

1Department of Mechnical Engineering2NUS Graduate School for Integrative Sciences and Engineering

Remote maintenance enables disparately located workers to collaborate withone another on maintenance tasks, and Augmented Reality (AR) technologycan provide a useful interface between virtual and real worlds to facilitate thesetasks. In this interdisciplinary research, an AR-assisted remote maintenancesystem will be designed and developed. Such a system will enable the on-siteworker to retrieve related information (e.g., maintenance procedures) that canbe augmented virtually with the real equipment, collaborate with the remoteoperator via intuitive multimedia files (e.g., videos and 3D models) in additionto verbal communication, and interact with the system and databases via anintegral user interface. This research aims to explore the benefits of applyingAR technology in maintenance operations and design the necessary interfacesneeded. Related key research issues include tracking and registration, collabo-rative system design, human-system interaction, information filtering, mainte-nance data management, etc. Thus far, an online authoring tool, Online Author-ing for Augmented Reality Remote Maintenance (OAR2M), has been partiallydesigned and developed. OAR2M enables the user to create 3D augmentations(e.g., animating virtual replicas of real objects) without a-priori knowledge ofthe environment, and such augmentations enable more intuitive and efficientcollaboration 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 virtualobjects to create an AR environment where the users can interact with bothtypes of objects. In this research, an AR 3D design space will be developedtogether with complementary design theories and methodologies. By applyingAR technology in a design space, an interactive conceptual design environmentcan be created to provide intuitive interaction tools for concept modeling, multi-modal visualization and contextualization of augmented prototypes and com-prehensive product information during conceptual design. Such a design spacewill be simple enough for the layman to carry out design tasks. Thus, the cus-tomers will be able to participate in the conceptual design stages as designersand 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 andthe aim of the research is to create an AR 3D design space that is suitable foruse by children.

Key technological areas covered in the research include 3D tracking, 3Dreconstruction and modeling, interaction techniques in AR and multi-modalproduct visualization. In the past two years, these areas have been analyzed andintegrated to design and develop two applications, namely AR Computer-AidedDesign Environment (ARCADE) and Gesture-based AR Design Environment(GARDE), which demonstrate the use of AR in design. By matching the benefitsof using AR with the requirements of conceptual design, this research aims toadvance the knowledge in both fields and create new ways of conceptual design.

59

POSTER 43

Electrophysiological consequence of geneticperturbation in gastrointestinal diseases — a

computational investigation

Poh Yong Cheng1,2, Martin Buist1,2

1Division of Bioengineering2NUS 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 portionof the population. Sustained sufferance of such disorders lowers quality of life(e.g. pain, poor nutrition) and incurs direct and indirect economic and socialcosts. The poor understanding of mechanisms underlying gastrointestinal dis-orders hampers effective treatment and patient management. Computationaltechniques are an increasingly popular approach that contributes to uncover-ing etiology and complements traditional biological experimental methods. Ofparticular importance is the capability of computational methods to integratevast amount of experimental data, across spatial and temporal scales, to under-stand how components of a system interplay to engender physiology or patho-physiology. In the context of the gastrointestinal tract, recent epidemiologicalstudies and genetic studies have suggested that mutations of the sodium chan-nel protein complex could potentially contribute to functional gastrointestinaldisorders. Heterologous expression systems in HEK cells found these muta-tions altered sodium channel electrophysiology, which raised further questionsas to how the same mutations could adversely affect gastrointestinal cells. Acomputational framework was used in an initial attempt to evaluate the electro-physiological consequence of these mutations. Mutation altered sodium channelelectrophysiology was modeled and verified. Subsequently, the sodium channelmodel was integrated into gastrointestinal cell models and in silico experimentswere performed to evaluate the impact of these mutations. Electrics affects me-chanics and therefore a genetic perturbation may lead to disrupted electrics anddysmotility at the global scale.

60

POSTER 44

Magnetism and Magnetotransport Studies inGe0.9Mn0.1Te

Lim Sze Ter1,2, J. F. Bi2, K. L. Teo2, and T. Liew2,3


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 basisof future semiconductor spintronic technologies which promise integration ofmagnetic, semiconducting and optical properties and a combination of informa-tion processing and storage functionalities. However, it has been a challenge togrow homogeneous ferromagnetic semiconductors epilayers and with high Curietemperature (Tc). The formation clusters is often observed in semiconductorsdoped with transition metals. These condensed magnetic semiconductors orclusters can be in the form of observable secondary phases or regions of subtlespinodal decomposition. The high quality of these epilayers is highly depen-dent on the growth conditions. In IV-VI ferromagnetic semiconductor such asGe1−xMnxTe, two different growth conditions with the same Mn concentrationof 8% can lead to different magnetic properties and Curie temperatures. Thetemperature dependence of magnetization (M-T) had showed one with concaveand other with convex behavior, which was suggested to have a short rangeand long range ferromagnetism, respectively. We have investigated the mag-netic and magnetotransport properties of Ge1−xMnxTe (x = 0.1) grown bymolecular-beam epitaxy. Our results show that the sample exhibits two ferro-magnetic transition temperature at Tc = 34 K and Tc * = 100 K. We infer thatTc is a long range ferromagnetic ordering in view of sufficient carriers generat-ing uniform ferromagnetism while Tc * is a short range ferromagnetic orderingdue to ferromagnetic clusters. The temperature dependence of the resistivity(ρ-T) curve exhibits a shallow minimum near Tc. The upturn of ρ-T the lowtemperature (T < Tc) is well described by a weak-localization model while inthe high temperature regime (T > Tc), the phonon scattering dominates.

61

POSTER 45

Multi DOF Active Vibration Isolation and itsApplication in Precision Pointing of Flexible

Spacecrafts

Liu Lei1, K K Tan2, S Huang, T H Lee1NUS Graduate School for Integrative Sciences and Engineering


Passive vibration isolation is inadequate for precision engineering applicationswith strict requirements, especially in handing random and low frequency dis-turbances. There is also trade-off problem between base vibration isolation andpayload disturbance rejection. However, active vibration isolation can overcomethese shortcomings. In this paper, multi degree-of-freedom (DOF) active vibra-tion isolation and its application in spacecrafts is presented. Model referenceadaptive control(MRAC) with acceleration feedback is used to isolate randomdisturbance. PID control is augmented with displacement feedback to suppressvibration displacement. The MRAC-PID composite control is applied to a 4-leg platform to isolate vibrations and suppress tip/tilt jitters. The scheme isused 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 andOptical Properties of Indium Oxide

Nanocrystals

Zhang Shuangyuan1, Ye Enyi2, Han Mingyong2,3

1NUS Graduate School for Integrative Sciences and Engineering2Institute of Materials Research and Engineering, Agency for Science Technology

and Research3Division of Bioengineering

In our research, weak acids, weak bases or their mixtures were used as reactionmedia/coordinating ligands to achieve a systematic morphological control ofamphoteric 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 irregularaggregated nanoparticles and uniform regular/truncated octahedrons, etc. Inaddition to their strong size-dependent absorption, single-crystalline indium ox-ide octahedrons also gave a strong band-edge emission while irregular indiumoxide aggregated nanoparticles only exhibited a weak deep-trap emission. Mean-while, the truncated octahedrons were self-assembled into either zigzag lines orpentagram patterns, and the regular octahedrons and truncated cubes wereself-assembled into hexagonally packed nanocrystal arrays. In addition, the for-mation mechanism of the various nanostructures under different conditions wasinvestigated in details.

63

POSTER 47

Genome-scale Modeling and in silico Analysisof 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 expres-sion system for recombinant glycoprotein production. As glycoproteins are keyproducts in the biopharmaceutical industry, there is great interest in develop-ing an efficient technology for manufacturing these biomolecules. Experimentalprotocols have been established over the past decades to study and engineerP. 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 silicometabolic model, based on the genome of P. pastoris, to serve as a platformfor rational design and analysis of the organism for various biotechnological ap-plications. Following a systematic procedure, we reconstructed a genome-scalemetabolic model which accounts for 668 genes, 1,177 metabolites and 1,361 re-actions that are appropriately segregated into eight subcellular compartments.Computational simulations of cellular phenotype, using constraints-based fluxanalysis, agree well with our experimental observation carried out in a chemo-stat and other existing literatures. Metabolite-centric analysis allowed us togain insight into the metabolism of P. pastoris and propose potential strate-gies to enhance its metabolic capabilities for recombinant protein productionand also biotransformation, which is the use of the microorganism to performchemical modification. In conclusion, the novel genome-scale metabolic modelof P. pastoris is a useful tool for studying cellular metabolism and developingrational metabolic engineering strategies for strain improvement. Due to thecomplexity of the metabolic network, the computational approach allows us toidentify non-intuitive targets for genetic manipulation and gain valuable insightsinto the sophisticated metabolic functions of the organism.

64

POSTER 48

Quantitative Analysis of Surface PluripotentMarker Expression on Human Embryonic Stem

Cells (hESCs) during Differentiation UsinghESC - Specific Antibodies

Lesley Y Chan1,2,3, Evelyn KF Yim2,4,5, Andre B Choo1,2,3

1NUS Graduate School for Integrative Sciences and Engineering2Bioprocessing Technology Institute

3Division of Bioengineering4Department of Surgery

5RCE Mechanobiology

Human embryonic stem cells (hESCs) have great potential for regenerativemedicine, but accurate identification and isolation of cell populations are firstrequired. Currently, there are five accepted markers for undifferentiated hESCs;unfortunately, these markers also identify embryonal carcinomas and/or mouseESCs. Therefore, our group generated a panel of monoclonal antibodies whichare specific to undifferentiated hESCs. However, the sensitivities of the antibod-ies to the undifferentiated hESC state have not been quantified. The sensitivityof hESC markers has usually been evaluated by the percentage of positively flu-orescing cells; but, a protein expression threshold level may be the determiningfactor of the cell state. Thus, it may be more accurate to quantify the proteinexpression level rather than the percentage of fluorescing cells when evaluatinghESC and define sensitivity as the rate at which the marker expression changeswith differentiation. This study aims to quantitatively analyze the sensitivityof the new panel of antibodies by evaluating the median fluorescence of surfaceantigen expression as the hESCs undergo spontaneous, hepatic, chondrogenic,and neural differentiation. We profiled the expression of six antibodies — mAb5, mAb 84, mAb 85, mAb 529, anti-SSEA1, and anti-Tra-1-60 — using flowcytometry 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 expressionduring differentiation. The sensitivity analysis indicated that mAb 84 and anti-Tra-1-60 are the strongest negative indicators for differentiation, while mAb 5and anti-SSEA1 are strong positive indicators. We envisage that through theseanalyses, we will be able to identify and separate sub-populations of hESCsduring differentiation; and more importantly, determine at which stage hESCtumorigenicity is eliminated.

65

POSTER 49

Hybrid Control for Unmanned Helicopters

Ali Karimoddini1, Lin Hai2, Ben Chen2, T. H. Lee2


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

66

POSTER 50

Soft Tissue Discrimination in MagneticResonance Elastography Using a New Elastic

Level Set Model

Li Bing Nan1, Chui Chee Kong2, Ong Sim Heng3,4, NumanoTomokazu5, Washio Toshikatsu6, Kobayashi Etsuko6

1NUS Graduate School for Integrative Sciences and Engineering2Department of Mechanical Engineering

3Department of Electrical and Computer Engineering4Division of Bioengineering

5Radiology, Tokyo Metropolitan University, Japan5Biomedical Imaging, National Institute of Advanced Industrial Science &

Technology, Japan6Biomedical Precision Engineering, University of Tokyo

Magnetic resonance elastography (MRE) noninvasively images the propagationof mechanical waves within soft tissues. The elastic properties of soft tissues canthen be quantified from MRE wave snapshots. Various algorithms have beenproposed 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 setmodel to directly detect and track abnormal soft tissues in MRE wave images.It is derived from the Mumford-Shah functional, and employs partial differentialequations for function modeling and smoothing. This level set model can in-terpret MRE wave images without elasticity reconstruction. The experimentalresults on synthetic and real MRE wave images confirm its effectiveness for softtissue discrimination.

67

POSTER 51

Design and Engineering of Cellulose EsterMembranes for Forward Osmosis

Zhang Sui1, Wang Kai Yu1, Chung Tai-Shung1, Y. C. Jean2, ChenHongmin2

1Department of Chemical and Biomolecular Engineering2Department of Chemistry, University of Missouri-Kansas City

Worldwide attention has been paid to forward osmosis (FO) in recent years asa prospective desalination technology for the production of fresh water. Withosmotic pressure as the driving force, FO possesses unique advantages of lowenergy consumption, anti-fouling property and high rejection towards ion con-taminants. However, currently available membranes for FO application sufferfrom severe internal concentration polarization (ICP) due to their thick andlow-porosity support layer, which leads to significant reduction in the efficiencyof osmotic driving force. Therefore, innovations are urgently required in thedesign and fabrication of membranes that are structurally feasible for FO. Thiswork has investigated the fundamental science of phase inversion and formationmechanism of cellulose ester membranes at the interface between polymer andcasting substrate. It also explores the desired membrane preparation condi-tions for forward osmosis (FO) applications in seawater desalination. With theaid of positron annihilation spectroscopy (PALS) and molecular simulation, thesimilarity in physicochemical properties between the polymer and the substratewas found to play a significant role in determining the porosity of the bottominterfacial layer. The structure of the dense interfacial layer was also strongly de-pendent on membrane thickness and solvent composition. Experimental resultssurprisingly reveal that the original pore size of the as-cast membrane plays acritical role determining the final performance of the subsequent annealed mem-brane independently of annealing temperature and time. In addition, since athreshold pore size exists during annealing above which pores become difficultto down size, we have found that a thin dense selective layer integrally in anasymmetric membrane may not always be the best option for FO applications.A balanced membrane structure consisting of a thin porous support and a thindense selective layer with a small structure parameter has been developed whichshows low internal concentration polarization (ICP) in the FO process. There-fore, a relatively high water flux was observed when seawater was employed asthe feed, indicating that the membrane has great potential for desalination.

68

POSTER 52

Polyelectrolyte Microcapsules for in VitroDelivery of Basic Fibroblast Growth Factor

Zhen She1,2

1NUS Graduate School for Integrative Sciences and Engineering2 Institute of Materials Research and Engineering (IMRE)

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

69

POSTER 53

Semi-interpenetrating Network (SIPN) ProtonExchange Membranes Based on

Poly(2,6-Dimethyl-1,4-Phenylene Oxide)

Fang Chunliu1,2

1Department of Chemical and Biomolecular Engineering2NUS 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©. AlternativePEMs with high proton conductivity but lower methanol permeability canbe the game-changer. This presentation summarizes our recent findings onthe 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 obtainedby penetrating a linear or branched polymer into one or more cross-linked poly-mer network. The inter-chain entanglement can endow the SIPNs with forciblecompatibility and mechanical stability. In our case, a series of PPO-based SIPNmembranes were prepared by interpenetrating the sulfonated PPO moieties ina hydrophobic network of brominated PPO that was covalent cross-linked byethylenediamine. Dynamic mechanical analysis (DMA) and differential scanningcalorimetry (DSC) were used to evaluate the thermal transitions and mechanicalrelaxations of the composite membranes. The SIPN construction successfullyinhibited methanol permeation through the membranes and improved the mem-brane dimensional stability by averting excessive swelling until 80 oC. Comparedwith Nafion c©, the PPO-based SIPN membranes showed comparable protonconductivity and maximum power density but with a much lower methanol per-meability. The PPO-based SIPN membranes have therefore acquired the basicphysicochemical properties which are required for DMFC applications.

70

Poster Presentations:Medicine

71

POSTER 54

Regulation of Cullin RING E3 Ubiquitin Ligasesby CAND1 In Vivo

Boon Kim Boh1, Yee Shin Chua2, Wanpen Ponyeam2, ThiloHagen2

1NUS Graduate School for Integrative Sciences and Engineering2Department of Biochemistry, Yong Loo Lin School of Medicine

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

72

POSTER 55

Functional Effects of a Novel BIMPolymorphism in Mediating Resistance to

Tyrosine Kinase Inhibitors in ChronicMyelogenous 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 GraduateMedical School

2Genome Institute of Singapore, Agency for Science, Technology and Research

Most patients with chronic myelogenous leukaemia (CML) respond to therapywith BCR-ABL tyrosine kinase inhibitors (TKIs). However, about 15-20% ofpatients will eventually develop resistance to TKIs. Previously, we identifieda novel polymorphism in the pro-apoptotic gene, BIM, which correlated withclinical resistance to TKIs. KCL22, a CML cell line that harbours the polymor-phism, was used to investigate the functional effects of the BIM polymorphism.Initial experiments confirmed that KCL22 cells were highly resistant to TKIswhen compared to cells without the polymorphism. Based on the gene structureof BIM, we predicted that the polymorphism would influence splicing betweenexons 3 and 4 in a mutually exclusive manner, an event that could affect celldeath decisions since the pro-apoptotic BH3 domain is found only in exon 4.Consistent with this model, we found that KCL22 cells expressed increased exon3- versus exon 4-containing transcripts compared to wildtype cells, a result mir-rored in CML patient samples. We next found that the decreased expressionof exon 4-containing transcripts was associated with decreased protein expres-sion of pro-apoptotic forms of BIM, including BIMEL, and that knockdownof exon-3 containing transcripts did not sensitize KCL22 cells to TKI-inducedapoptosis. These results suggested that TKI-resistance in KCL22 cells was dueto impaired expression of BH3-containing BIM isoforms. Consistent with thisnotion, we found that BH3 mimetics sensitized KCL22 cells to TKI-inducedapoptosis. Our results offer mechanistic insights into how the BIM polymor-phism mediates TKI-resistance; a resistance that we show can be overcome byBH3 mimetics.

73

POSTER 56

Regulation of C1q Expression at Transcriptionaland Epigenetic Levels

Tan Shurong Carol1,2, Lu Jinhua2

1NUS Graduate School for Integrative Sciences and Engineering2Department 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. Mostnotably, a deficiency in C1q is associated with the development of systemiclupus erythematosus (SLE) for which the underlying mechanism is unclear.An interesting property of C1q is its production by dendritic cells (DCs) andmacrophages, the two major types of antigen presenting cells (APCs). A de-fect in C1q production by these cells may significantly alter host tolerance toself-antigens. Hence, exogenous and endogenous factors that influence C1q pro-duction in these cells can potentially affect the onset of SLE.

In mouse BMDCs, we observed the mRNAs of C1qA, C1qB and C1qC wereco-ordinately regulated by microbial structures, hormones and cytokines. Anotable feature is that the three C1q subunit genes are closely clustered on thechromosome, although how this may facilitate the coordinated expression of thethree genes remains unknown. We postulate that the C1q genes behave as agene cluster to achieve synchronized expression.

To investigate the underlying mechanism, we first identified promoter andregulatory elements involved in the regulation of each C1q subunit genes. Thetranscriptional start sites (TSS) of the three C1q genes were determined andthe putative promoter regions were each cloned into PGL3 luciferase reportervector. All three promoters exhibited basal activity, suggesting that each C1qsubunit gene has an independent promoter. However, only the activity of C1qBpromoter was up-regulated by interferon-gamma (IFN-γ) even though all threeendogenous C1q mRNA levels increased in BMDCs. An IFN-γ regulatory sitewas indeed identified 5’ to the C1qB basal promoter region.

74

POSTER 57

Structural Refolding of Hepatitis B Virus XProtein (HBx)

Oh Man Huan Veronica1,2, Ren Ee Chee1,3

1Department of Microbiology, Yong Loo Lin School of Medicine2NUS Graduate School for Integrative Sciences and Engineering

3Laboratory of Immunogenetics, Singapore Immunology Network, Agency for ScienceTechnology and Research

Chronic Hepatitis B virus (HBV) infection, which affects approximately 350 mil-lion people worldwide, is strongly associated with the development of hepatocel-lular carcinoma (HCC). However, the mechanisms underlying the oncogenicityof 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 associatedwith the development of HCC. HBx is reported to be a multi-functional proteinthat modulates a wide variety of cellular pathways and also interacts directlywith many host proteins. To date, however, the precise function and structureof HBx is still undefined. Since HBx does not bind directly to DNA and manyof the cellular functions HBx modulates is via protein-protein interactions, itis important to elucidate the structure of HBx. HBx sequence was first clonedinto pET-28a(+) vector and transformed into E. coli strain BL-21 cells for largescale bacterial expression. E. coli cells were then lysed and inclusion bodiescontaining the expressed HBx protein were washed and solubilized in 6M guani-dine denaturation buffer. The denatured HBx protein was then subjected to awide variety of refolding conditions to refold the protein optimally. With theoptimization of the refolding conditions, HBx protein was showed to acquire anunprecedented structural refolding, possessing a β-sheet secondary structure asdemonstrated by its characteristic CD spectra. The refolded HBx protein canthus be purified and have its structure determined by nuclear magnetic reso-nance spectroscopy (NMR) or X-ray crystallography. The elucidation of the 3Dstructure of HBx protein would thus allow us to understand the spatial inter-actions between HBx and its binding proteins and to observe if HBx undergoesstructural changes as it binds to its multiple cellular partners. The search ofa structural homolog of HBx may also aid in the identification of the exactfunction of the multi-functional HBx protein.

75

POSTER 58

Identification and Functional Analysis of AP2γ

as a Novel Transcriptional Cofactor of EstrogenReceptor 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 Medicine2Cancer Biology and Pharmacology

3NUS Graduate School for Integrative Sciences and Engineering4Genome Institute of Singapore, Agency for Science Technology and Research

5Department of Biological Sciences6Computational and Mathematical Biology Group

Estrogen receptor (ER) transcription is fundamental to regulation of breast can-cer development and progression. To understand the mechanism of ER tran-scription, 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 influencedthrough cooperation with multiple transcription factors, we are interested inuncovering potential novel ERα collaborating factors. Hence, we performedcofactor motif analysis by scanning the ERBSs identified by ChIP-seq withTRANSFAC motif matrices. Our analysis revealed binding sequences of AP2family of transcription factors (GCCYNNGGS) as significantly enriched in theERBSs. The AP2 family of transcription factors orchestrate a variety of cellularprocesses, including cell growth, cell adhesion and tissue differentiation. AP2γ(TFAP2C), a member of the AP2 family, was reported to be over-expressedin breast carcinoma and recently shown to promote breast tumour cells pro-liferation. However, little is known on how it regulates transcription in breastcancer. Here, using a combination of RNA interference, ChIP and Chromosomeconformation capture (3C) assays, we aim to study how AP2γ regulates ERαtranscription of RET (rearranged during transfection), an estrogen-responsivegene, in MCF-7 cell line.

76

POSTER 59

Understanding the Regulatory Network ofAndrogen Receptor and TMPRSS2-ERG Fusion

Protein in Prostate Cancer Progression

Chng Kern Rei1,2, Tan Si Kee1,2, Chang Cheng Wei1,2, YangChong1,2, Hong Shuzhen1, Edwin Cheung1,2

1Genome Institute of Singapore, Agency for Science Technology and Research2NUS Graduate School for Integrative Sciences and Engineering

Deregulation of the AR (Androgen Receptor) transcriptional network is a com-mon hallmark in prostate cancers. AR is a master transcription factor thatorchestrates a circuitry of genes mediating cellular proliferation, differentiation,motility and survival. To achieve its precise transcriptional role, AR needs toco-operate specifically with a plethora of co-factors. In prostate cancers, ARtranscription collaborators are frequently aberrantly expressed, altering the ARsignaling pathway to one that promotes oncogenesis. Recently, it was discoveredthat the majority of prostate cancers harbour a recurrent gene fusion betweenTMPRSS2, an AR target gene and ERG, a member of the ETS family of tran-scription factors. Consequently, ERG is induced upon androgen stimulation.To study the potential cancer-specific transcriptional collaboration between ARand ERG, we adopted a ChIP-Seq approach. We observed increased recruitmentof ERG to a substantial portion of AR binding sites after androgen stimulation,indicative of its role as an AR transcriptional collaborator. ERG was foundto directly repress AR expression. In addition, ERG was also found to actas an inhibitor of AR transcriptional activity. Currently, our work suggeststhat over-expression of ERG might impede AR-induced epithelial differentia-tion and enhance epithelial mesenchymal transition (EMT) in prostate cancercells, thereby conferring a more aggressive and invasive phenotype.

77

POSTER 60

Bcl-2 Modulates Resveratrol-induced ROSProduction 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 Medicine2NUS Graduate School for Integrative Sciences and Engineering

3Cancer ans Stem Cell Biology Program, Duke-NUS Graduate Medical School4Singapore-MIT Alliance

Resveratrol is a naturally occurring flavanoid with potent apoptosis inducingactivity against human tumor cells. We investigated the effect of resveratrolon human leukemia cell lines, in particular its ability to induce intracellularreactive oxygen species production and the effect of Bcl-2 overexpression onthis model. Exposure of CEM cells to increasing concentrations of resvera-trol (0-50µM) resulted in an increase in mitochondrial superoxide production,decrease in mitochondrial biogenesis and transmembrane potential, and a con-comitant decrease in cell viability. Whereas overexpression of Bcl-2 increasedmitochondrial oxygen consumption and complex IV activity, CEM/Bcl-2 cellsresponded to the increased mitochondrial oxidative stress induced by resver-atrol by significantly reducing mitochondrial respiration, complex IV activityand superoxide production, and promoted cell survival. The inhibitory effect ofBcl-2 on resveratrol-induced mitochondrial superoxide production is further cor-roborated by the neutralization of this regulatory effect upon siRNA mediatedgene silencing of Bcl-2. These data provide evidence implicating mitochondrialmetabolism in the anti-cancer activity of resveratrol, and underscore a novelregulatory role of Bcl-2 against exogenous oxidative stress through its ability tofine tune mitochondrial respiration, and by doing so maintaining mitochondrialsuperoxide at a level optimal for survival.

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POSTER 61

A Novel Role for RUNX3 in the Regulation ofIL23A

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 Singapore2NUS Graduate School for Integrative Sciences and Engineering

3Institute of Molecular and Cell Biology, Agency for Science, Technology andResearch

RUNX3 is a prominent tumour suppressor in gastric epithelium where its inac-tivation is observed in ¿80% of human primary gastric cancers. As an importantregulator of gastric epithelial cell growth and apoptosis, we have previously re-ported that RUNX3 regulates key target genes, p21 and Bim1. However, the fullgenetic programme maintained by RUNX3 in the gastric epithelium remains tobe fully elucidated. As a step towards this, we conducted an expression microar-ray study, which measured transcriptomic changes following the re-introductionof RUNX3 into a non-expressing cell line. Here, we report the identificationof a novel RUNX3 target gene, IL23A. IL23A encodes the unique subunit ofInterleukin-23 (IL-23) known to play a key role in immune surveillance againstpathogens in the gastrointestinal tract. We posit that RUNX3 exercises its tu-mor suppressive function in part through a direct regulation of this gene. In ourvalidation study, we observed the induction of IL23A by RUNX3 across multiplecancer cell lines, implicating an important role. Through reporter assays, wedemonstrated the functions of three RUNX binding sites on the IL23A proxi-mal promoter. In this assay system, we observed the transactivation of IL23Apromoter 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 usingmobility shift assay and confirmed by chromatin immunoprecipitation. Lastly,we performed RNAi knockdown of RUNX factors in the established cell modelto demonstrate their involvement in the regulation of IL23A expression and IL-23 secretion. Given the importance of IL-23 in mucosal immunity, we postulatethat RUNX proteins play a multi-facet role in maintaining the homeostasis inthe mucosal barrier and immune surveillance in the gut.

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POSTER 62

Characterization of the Role of E7 inTranscriptional Regulation of Mitotic Genes

Pang Chai Ling1, Teissier Sebastien2, Thierry Francoise2

1Department of Microbiology, Yong Loo Lin School of Medicine2Institute 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 HPVhas been attributed to oncogenic activities of E6 and E7. E6 mediates p53degradations whereas E7 stimulates cell cycle progression via pRB inactivation.Previous studies have demonstrated that E7 can up-regulate E2F target genesand promote S-phase entry by subverting pRB/E2F pathway. Recent microar-ray findings implied that E7 also plays a significant role in the modulation ofmitotic genes but the molecular mechanism remains elusive. This data wasvalidated by our PCR array experiment and the results showed that E7 hasprofound effect in cell cycle regulation. In addition, B-Myb and FoxM1 areE2F target genes as well as the major transcription factors for regulation ofmitotic genes. We have characterized role of B-Myb and FoxM1 in cervicalcarcinogenesis through siRNA-mediated depletion of gene expression and thisdata indicates that B-Myb plays a more dominant role in regulation of mitoticgene expression. E7 can promote mitotic entry via downstream effectors, suchas B-Myb and FoxM1 but we do not exclude the possibility that E7 may ex-ert direct effects on gene regulation of mitotic genes. We also found that E7can interact and co-localize with B-Myb in nucleus from immunoprecipitationand immunofluorescence assay. In addition, we have performed chromatin im-munoprecipitation and we confirmed that E7 can bind to promoter region ofmitotic genes. Collectively, our results suggest that E7 can be directly recruitedto promoter of mitotic genes in association with B-Myb, FoxM1 and/or otherputative interactors. This understanding of interplay between E7, B-Myb andFoxM1 would enable us to fully delineate the underlying mechanism of malig-nant transformation of HPV infection in order to develop the novel therapeutictargets for combating cervical cancer.

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POSTER 63

Identification of Recurrent Regions of CopyNumber Variants Across Multiple Individuals

Teo Shu Mei1,2, Agus Salim1,2, Yudi Pawitan1,2

1Department of Epidemiology and Public Health2NUS Graduate School for Integrative Sciences and Engineering

Identification of common copy-number polymorphisms regions using high den-sity SNP array. SNP arrays and array comparative genomic hybridization(aCGH) arrays are widely used technology platforms for CNV detection. TheCNVs are usually detected per sample, and because of the high noise level in theintensity values, the boundaries of the detected CNVs tend to vary among indi-viduals. However, common CNV regions are likely to occur at the same genomiclocation across different individuals. Common algorithms used with SNP arraydata, for identifying individual CNV regions, such as PennCNV, report the logBayes factor as a confidence score for each identified CNV; these scores provideevidence of the reliability of a CNV within an individual. Previous methodsof 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 samplescontribute equally to the statistic used to identify the common regions, but infact, there is inter-sample variability, where some individual regions are morelikely to be true/false positives. We develop three new approaches for identi-fying common CNV regions that are recurrent to all or an unknown subset ofsubjects. The methods take segmented data as the input. The first method es-timates a statistic based on the frequency of occurrence of reliable CNVs, wherereliability is determined by high confidence scores. The second method is basedon a weighted frequency of occurrence of CNVs, where the weights are deter-mined by the confidence scores. The last method is motivated by the fact thatwe sometimes observe partially overlapping CNV regions as a mixture of twoor more distinct subregions; it is based on a clustering algorithm applied to thecommon regions found in the first or second method. The identified commonregions can then be used for downstream analysis such as group comparisons inassociation studies.

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POSTER 64

Dengue Virus Neutralization in HumanMonocytes

Chan Kuan Rong1,2, Zhang Li-Xin3, Tan Hwee Cheng1, BrendonHanson3, Mariano A Garcia-Blanco1, Ooi Eng Eong1

1Duke-NUS2NUS 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 twopossible extreme outcomes: either virus neutralization which protects the hostfrom dengue infection, or enhancement of infection in monocytes which resultsin increased disease severity. However, the determinants of successful virus neu-tralization in the context of Fc-gamma receptor bearing cells, which are targetsof the virus, is incompletely understood. We investigated the early intracellu-lar events of dengue immune complexes following interaction with THP-1 cellsto understand how virus-antibody complexes are neutralized in human mono-cytes. Using a mouse-human chimeric antibody against DENV-2, we observedthat antibody concentration affects the size of the immune complexes formed,which results in different Fcγ-receptor (FcγR) engagement. Larger immunecomplexes appear to cross-link FcγRIIB, which inhibits internalization of im-mune complexes in monocytes. Increase in internalization was observed whenthe antibody concentration was reduced, as immune complex size results in di-minished cross-linking of FcγRIIB. Collectively, our studies provide a novel toolto investigate early intracellular events between antibody-virus complexes andmonocytes, and provide some mechanistic insights into dengue virus neutraliza-tion in human monocytes.

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POSTER 65

Sustained High Levels of IL-6 Contribute to thePathogenesis of Enterovirus 71 in a Neonate

Mouse Model

Khong Wei Xin1, Damian G. W. Foo1, Tan Eng Lee2, SylvieAlonso1

1Department of Microbiology, Immunology Programme, Yong Loo Lin School ofMedicine

2School of Chemical and Life Sciences, Singapore Polytechnic

Enterovirus 71 (EV71) is the major causative agent of Hand, Foot and MouthDisease (HFMD) in young children, and has been consistently associated withthe most severe complications of the disease, which include central nervous sys-tem inflammation, and pulmonary edema. Increasing frequency and amplitudeof EV71 outbreaks have raised awareness and concerns worldwide. Previousreports proposed that overwhelming virus replication combined with the induc-tion of massive pro-inflammatory cytokines is responsible for the pathogenicityof EV71. Specifically, elevated IL-6 levels were observed consistently in patientsand strongly correlated with disease severity. In this study, we showed in theneonate mouse model that sustained high levels of IL-6 produced upon EV71infection are detrimental to the host, leading to severe tissue damage, and even-tual death to the animals. Administration of anti-IL-6 neutralizing antibodiesafter the onset of the clinical symptoms successfully improved survival rate andclinical score of the infected hosts. In addition, compared to non-treated con-trols, anti-IL-6 treated mice displayed reduced tissue damage and absence ofsplenic atrophy. Upon anti-IL-6 treatment, transient markedly increase in IL-10 levels was measured. Furthermore, there was no significant difference invirus titers between anti-IL-6 treated and non-treated mice, indicating that theanti-IL-6 antibody-mediated protection is independent of the virus load. Ourfindings thus demonstrated that IL-6 plays a major role in EV71-induced im-munopathogenesis. Furthermore, as there is still neither vaccine nor treatmentavailable against EV71, anti-IL-6 antibody treatment may represent a possi-ble therapeutic approach to prevent from the most severe complications of thedisease.

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POSTER 66

Role of Rac1 in Regulating Bcl-2 MediatedChemoresistance and Pro-oxidant State in

Tumour Cells

Kang Jia1,2, Rathiga Velaithan2, Jayshree L. Hirpara2, CatherineBrenner3, Marie Veronique Clement4, Shazib Pervaiz1,2,5,6

1NUS Graduate School for Integrative Sciences and Engineering2Department of Physiology, Yong Loo Lin School of Medicine

3Faculte de Pharmacie, Universite Paris4Department of Biochemistry, Yong Loo Lin School of Medicine;

5Duke-NUS6Singapore-MIT Alliance

We have previously reported that Bcl-2 expression resulted in an increase in in-tracellular superoxide anion and that a dominant negative mutant of the smallGTPase Rac1 sensitized Bcl-2 expressing cells to apoptosis. Here we reportthat silencing and functional inhibition of Rac1 blocks Bcl-2 mediated increasesin intracellular and mitochondrial superoxide levels in tumor cells. We provideevidence that this effect is mediated via specific interaction between the two pro-teins using coimmunoprecipitation, confocal and electron microscopy, as well asGST-fusion proteins. Analysis of the sub-cellular localization of these proteinsrevealed increased association of Bcl-2 and mitochondrial Rac1 in Bcl-2 overex-pressing cells. This interaction can be blocked in vitro and in vivo by the BH3mimetics, HA14-I and BH3-I, as well as by synthetic Bcl-2 BH3 domain pep-tides. That this interaction is functionally relevant is supported by the abilityof the Bcl-2 BH3 peptide to inhibit intracellular superoxide production as wellas overcome drug resistance in Bcl-2 overexpressing cells. Lastly, using patientderived primary tissues, the interaction was observed only in cancerous tissueswith marked overexpression of Bcl-2 and not in peripheral blood leukocytes ornoncancerous primary tissue. These data provide a novel facet in the biology ofBcl-2 with potential implications for targeted anti-cancer drug design.

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POSTER 67

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

Zhou Fan1,2,3, Zhang Jinqiu1, Nathalie Escande-Beillard1, BrunoReversade1, Fu Xinyuann1,2,3, Alan Colmann1,2

1Institute of Medical Biology, Agency for Science Technology and Research2Department of Biochemistry

3NUS Graduate School for Integrative Sciences and Engineering

Wrinkly skin syndrome (WSS; MIM278250), also called Autosomal Recessivecutis laxa type II (ARCRL2; MIMI219100), is an autosomal recessive disor-der that is characterized by wrinkly skin (hands, feet and abdomen), decreasedelasticity of the skin, multiple skeletal abnormalities, microcephaly, and men-tal retardation (Casamassima et al. 1987). The latest report suggested thatWSS was caused by different mutations of PYCR1 (Reversade et al. 2009).Because WSS is exceptionally rare, biopsy material is not readily available andthe impact of the PYCR1 mutation on different cell types is difficult to assess.However, with the advent of induced pluripotent stem cells (iPSCs), multiplepatient-specific cell types can be made available. This provides us a new plat-form to model many human diseases (Colman and Dreesen, 2009).

In our study, we established an iPSC disease model for WSS. WSS fibroblastswere firstly reprogrammed into iPSCs using retrovirus-based method. For threeWSS cell lines, we got at least two different colonies for each cell line. To verifythe identity of all these colonies, various assays were performed to characterizeiPSCs, including expression study, methylation status study, karyotype analysis,teratoma formation assay. After completing the characterization of the iPSClines, currently, we are trying to investigating the cellular defects during thedisease development in the iPSC model, and hoping to uncover the molecularmechanism underlying WSS disease.

Reference:Casamassima AC, Wesson SK, Conlon CJ, et al. Wrinkly skin syndrome: phe-notype and additional manifestations. Am. J. Med. Genet. 27, 885-893 (1987).Colman A, Dreesen O. Pluripotent stem cells and disease modeling. Cell StemCell 5, 244-247 (2009).Reversade B, Escande-Beillard N, Dimopoulou A, et al. Mutations in PYCR1cause cutis laxa with progeroid features. Nat Genet. 41, 1016-1021(2009)

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Poster Presentations:Physics

87

POSTER 68

Quasi-Freestanding Epitaxial Graphene on SiCvia Fluorine Intercalation from a Molecular

Source

Wong Swee Liang1,2

1Department of Physics2NUS Graduate School for Integrative Sciences and Engineering

Epitaxial graphene on SiC(0001) is a promising route towards large scale fab-rication of graphene devices but is limited by the presence of an interactingsubstrate. Graphene-substrate interaction is mainly mediated by the interfaceSiC(0001) 6

√3×6

√3 R30◦ layer (buffer layer). Intercalation of the buffer layer

to form quasi-freestanding epitaxial graphene has been performed using sourcessuch as H2 to minimize this interaction. However, detailed STM studies havenot been conducted on these quasi-freestanding epitaxial graphene or its forma-tion process. In this report, fluorine intercalation of the buffer layer was carriedout using fluorinated fullerenes, C60F48, as a source of fluorine. The process ofgraphene formation via fluorine intercalation and its properties was investigatedusing Low Temperature Scanning Tunneling Microscopy (LT-STM), ScanningTunneling Spectroscopy (STS) and Photoemission Spectroscopy (PES). Quasi-freestanding epitaxial graphene with dilute fluorination was achieved after in-tercalation 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 thefirst time under LT-STM. PES reveal that the fluorine involved in the inter-calation remains in the substrate, possibly as a passivation layer between thefreestanding epitaxial graphene—SiC interface. The mechanism underlying theprocess will be discussed in detail with respect to the findings.

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POSTER 69

Structure and Mechanical Properties Study ofBombyx Mori Silkworm Silk Fibrils by Atomic

Force Microscope and X-ray Diffraction

Deng Qinqiu1,2

1Department of Physics2NUS Graduate School for Integrative Sciences and Engineering

The aim of this project is to unravel the micro-structure and mechanical prop-erties of the Bombyx mori silk fibril through atomic force microscopy and x-raydiffraction. Silk is a material with better properties than most of man-madefibers, 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 basicunit-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 de-sign of the silk fibril, and combining the structure information from the x-raydiffraction, we hope to figure out the structure model of the silk fibril andob-tain information about amino acid organization in the silk andits correspondingstructure.

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POSTER 70

Nanoparticles Fractionation using AlignedCarbon 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 Physics3Department of Chemistry

4Dunman High School5Division 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 distributionis presented. By dipping aligned CNT arrays into solution comprising differentsized quantum dots (QDs), size-selective gradient decoration of QDs onto CNTsis achieved. The fractionating capability of CNTs is also demonstrated for poly-dispersed manganese doped zinc sulphide nanoparticles and QDs of varying sizesand chemical compositions, which we attribute to the size-selective sieving effectof CNTs. By controlling the terminating point for the flow of QDs across theCNT array, QDs size specific CNT/QDs hybrid structure is achieved.

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POSTER 71

Experimental and Computational Studies ofFibroblast Migration on Compliant Substrates

Yip Ai Kia1, Chiam Keng Hwee2, Paul Matsudaira3

1NUS Graduate School for Integrative Sciences and Engineering2Biophysics, Institute of High Performance Computing, Agency for Science

Technology and Research3Department 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 cansense and respond to differences in stiffness during differentiation and migration.However, the mechanism which regulates these differences in cell behaviour isnot well understood. NIH3T3 fibroblasts were cultured on polyacrylamide sub-strates of different stiffness and fibronectin coating, and cell migration speed wascalculated. It was found that cells showed maximal speed at intermediate stiff-ness (7-13kPa). On soft substrates (≤ 7kPa), optimal fibronectin concentrationfor maximal cell speed occurs at 75µg/ml, whereas on stiffer substrates, optimalconcentration occurs at 25µg/ml. When the focal adhesion protein vinculin wasstained, total amount of vinculin was not significantly changed when substratestiffness is increased. However, vinculin form structures which increase in sizewith increasing stiffness. We hypothesized that increasing substrate stiffness donot affect total number of cell-substrate adhesions, but increases clustering ofbonds which reinforces adhesion strength. A computational model was used tosimulate cell detachment with various spatial distributions of adhesion bondsto the substrate, while keeping the number of cell-substrate adhesions constant.Simulation results showed that for the same detachment force, adhesion lifetimeis shorter when bonds are arranged in small clusters. However, when clustersare larger, due to cooperatively between neighbouring bonds, adhesion clusterlifetime is increased. We argued that on stiff substrate, larger focal adhesionsize resulted in stronger adhesion to the substrate, allowing the cell to exertmore traction forces to move forward as compared to cells on soft substrates.However, when adhesion to the substrate is too strong, adhesion lifetime isincreased, thus slowing down migration.

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POSTER 72

Dynamic-based Structure Measures on ComplexNetworks

Zhu Guimei, Li BaowenDepartment of Physics

Network topology structures play a crucial role in determining the emergenceof collective dynamical behaviour. It is the cornerstone for understanding therelationship between structures, functions and dynamics of complex networks.

We study the structural characteristics of complex networks using the rep-resentative eigenvectors of the adjacent matrix. The probability distributionfunctions of the components of the representative eigenvectors are proposed todescribe the localization on networks where the Euclidean distance is invalid.

Also, comparison of cellular networks can provide insights into biological un-derstanding and therapeutics. Dynamics on biological networks, as the bridgebetween structures and functions, occur generally from micro- to macro- struc-tural scales. Some measures of networks are proposed such as degree distribu-tion, shortest pathway, graphlet distribution and fractal, but how to describesimultaneously the structural patterns at different scales is still an open problem.For an electron moving in a large molecule, the eigenstates of the tight-bindingHamiltonian represent from low to high energy are used as probes of the struc-tural characteristics from macro- to micro- scales. Localization properties areused to characterize the eigenstates.

Being a measure of network structures, the structure-induced localizationmay also have potential applications in understanding the electronic propertiesof materials such as conductive polymers and carbon nanonets. The intrachainwindings in conductive polymers can introduce long-range edges into the originalone dimensional system, resulting in nontrivial network structures.

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Special thanks to

• Benjamin Mate Gyori

• Inosha Wickrama

• Joanne James

• Manickaratnam Ranjan

• Sampath Jeewantha Wijesinghe

• Yap Wen Lynn

3rd NGS Student Symposium February 28, 2011 · either oral or poster presentations and the...

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