Untitled - High Impact Research
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Untitled - High Impact Research
front.pdf 1 22/05/2012 4:49:51 HIR Annual report 2011.indb 2 24/05/2012 9:44:43 High Impact Research Annual Report 2011 1 HIGH IMPACT RESEARCH GRANT ANNUAL REPORT 2011 HIR Annual report 2011.indb 1 24/05/2012 9:44:43 HIR Annual report 2011.indb 2 24/05/2012 9:44:43 High Impact Research Annual Report 2011 Message from Chairman 7 Committee Members • Central • Faculty 8 9-13 HIR Advisory Council 14 List of Successful Applicants 2011 • HIRProjects–2Years • HIR-MoHEProjects–5Years 15 16-17 Research Proposal • (HIR2Years) • (HIR-MoHE5Years)FacultyofMedicine • (HIR-MoHE5Years)FacultyofEngineering • (HIR-MoHE5Years)FacultyofScience • (HIR-MoHE5Years)FacultyofDentistry • (HIR-MoHE5Years)FacultyofComputerScienceand InformationTechnology(FSCIT) • (HIR-MoHE5Years)Chancellory 20 46 68 96 109 120 125 Photo Gallery 138 International Collaborators 140 List of Publications 141 HIR Guidelines 146 SOP for the Management of HIR Fund 148 Procurement Process 149 Guidelines on Technical Evaluation 150 CONTENTS Cover Rationale HIRBuilding MarshallCentrein HIRBuilding ChancelloryBuilding 3 HIR Annual report 2011.indb 4 24/05/2012 9:44:43 High Impact Research Annual Report 2011 5 MESSAGE FROM CHAIRMAN COMMITTEE MEMBERS • • Central Faculty HIR ADVISORY COUNCIL LIST OF SUCCESSFUL APPLICANTS • • HIR Annual report 2011.indb 5 HIR2years HIR-MoHE5years 24/05/2012 9:44:43 HIR Annual report 2011.indb 6 24/05/2012 9:44:43 High Impact Research Annual Report 2011 7 LittledidIrealise,whenIinitiatedtheHighImpactResearch(HIR)programme for the university in February 2010, that it would grow into such a giant programme. It is just like the proverbial mustard seed which grew into a humongoustree! InAugustthisyear,theMinistryofHigherEducationMalaysia(MoHE)injected RM590millionintotheUMHIRprogrammefollowingtheCabinet’sdecision thatUMshouldbegiventhechancetobreakintothetop100worldranked universitiesin2015.Thatwehaveearnedthetrustofthegovernmentinsuch ashorttimeisquiteamiracleinitself.However,ittookalotofpersuasion onourparttojustifytheirfaith.FromAugusttoDecember2011,MoHEhas promisedtoreleaseRM40milliontoUMontheundertakingthattheuniversity topthiswithanotherRM40millionfrominternalfunds. ThefollowingfacultiessucceededingettingfundingthroughMoHE:Medicine, Dentistry,Science,EngineeringandComputerScience.Inaddition,8top-down research projects and one special project to purchase high-end equipment for central facilities were approved under the Chancellory HIR programme. A dedicated HIR Building is being readied to provide a more conducive environmentforsomeoftheflagshipprojectsfundedunderMoHE. UMisnowfacinga5-yearchallengetodeliverwhatitpromisedbyaccepting thisresearchfund.Amongthetargetswehavesetforourselvesincludeover 3,300Tier1ISIpublicationsbytheendof2015.AllPrincipalInvesitgatorshave signedapledgewiththeuniversitythattheywilldeliveronthetargets,orelse! Isthisanimpossibledream?Ibelievewecandoit,orfacethe‘choppingblock’. NoonethoughtthatUMcouldbreakintotheShanghaiJiaoTungUniversity Ranking this year, but we did. Under the QS World University Rankings, we managedtofinisharespectable167thisyear,asignificantjumpfrom207in 2010.ThepublicationrecordofUMstaffandstudentsisalsoontheriseandwe expecttocrossthe2,000publishedpaperssoon. MESSAGE FROM DR. GHAUTH JASMON ChairmanofHIRCommittee All these achievements could not have taken place without the hard work anddedicationofthestaffandstudentsofUM.Inaddition,wereceivedalot ofassistanceandencouragementfromourcollaboratorsoverseas,including academic icons from Ivy-League universities and eminently successful Malaysianresearchersabroad.WearealsoproudthatthreeNobelLaureates andonedistinguishedprofessorhaveagreedtoserveastheUMHIRAdvisory Council. UMiscertainlysolidlyontracktoachieveitsdreamtobeplacedintheTop100 Universitiesby2015andthenontohighersuccessesasweapproach2020. Bestpersonalregards. GHAUTH JASMON 31stDecember2011 HIR Annual report 2011.indb 7 24/05/2012 9:44:43 8 High Impact Research Annual Report 2011 Dr.GhauthJasmon Dr. Ghauth Jasmon (Chairman) HIR COMMITTEE CENTRAL Professor Dr. ProfessorDr. IshakAbdRazak Professor Dr. ProfessorDr. MohdAminJalaludin EmeritusProfessorDr. Emeritus Professor Dr. LamSaiKit EmeritusProfessorDr. Emeritus Professor Dr. YongHoiSen HalizaHarun Haliza Harun Azbullah Che Ibrahim AzbullahCheIbrahim NorshahidayuAli Norshahidayu Ali Secretariat,HighImpactResearchGrant Office of the Vice Chancellor, Level 9 Chancellory UniversityofMalaya,50603KualaLumpur www.hir.um.edu.my/ hirgrant@gmail.com ProfessorDr Professor Dr MohdAliHashim Siti Zawahir Zubir SitiZawahirZubir HIR Annual report 2011.indb 8 24/05/2012 9:44:44 High Impact Research Annual Report 2011 9 Professor Dr. Adeeba ProfessorDr.Adeeba Kamarulzaman (Chairman) HIR COMMITTEE FACULTYOFMEDICINE Professor Dr. Tunku ProfessorDr.Tunku KamarulZaman TunkuZainolAbidin Professor Dr. ProfessorDr. GohKheanLee Professor Dr. ProfessorDr. AmruNasrulhaqBoyce Secretariat,HighImpactResearchGrant, OfficeoftheDean,FacultyofMedicine UniversityofMalaya,50603KualaLumpur www.resfom.com/ hirgfom@ummc.edu.my EmeritusProfessorDr. Emeritus Professor Dr. YongHoiSen Assoc. Prof.Dr. Assoc.Prof.Dr. NoorAzuanAbuOsman HIR Annual report 2011.indb 9 ProfessorDr. Professor Dr. MohdAminJalaludin ProfessorDr. Professor Dr. IshakAbdRazak Siti Fatimah Zahra SitiFatimahZahra MohdAnuar 24/05/2012 9:44:44 10 High Impact Research Annual Report 2011 ProfessorDr. Professor Dr. MohdHamdiAbdShukor (Chairman) HIR COMMITTEE FACULTYOFENGINEERING Associate Professor Dr. AssociateProfessorDr. FaisalRafiqMahamd Adikan Professor Dr. ProfessorDr. MasjukiHajiHassan Professor Dr. ProfessorDr. NikMeriamNikSulaiman ProfessorDr. Professor Dr. MohdAminJalaludin ProfessorDr. Professor Dr. IshakAbdRazak ProfessorDr. Professor Dr. A.HamidA.Hadi Secretariat,HighImpactResearchGrant DeputyDean(Research)Office Level4,EngineeringTower FacultyofEngineering UniversityofMalaya,50603KualaLumpur engine.um.edu.my/ enghirmohe@gmail.com Professor Dr. ProfessorDr. AbdulKariemMohdArof HIR Annual report 2011.indb 10 Noorlainiewati Abdullah NoorlainiewatiAbdullah 24/05/2012 9:44:44 High Impact Research Annual Report 2011 11 ProfessorDr. Professor Dr. MohdSofianAzirun (Chairman) HIR COMMITTEE FACULTYOFSCIENCE Associate Professor Dr. AssociateProfessorDr. SithiV.Muniandy Professor Dr. ProfessorDr. ChongVingChing Professor Dr. ProfessorDr. NoorsaadahAbdul Rahman Secretariat,HighImpactResearchGrant OfficeoftheDean,FacultyofScience UniversityofMalaya,50603KualaLumpur fs.um.edu.my EmeritusProfessorDr. Emeritus Professor Dr. LamSaiKit ProfessorDr. Professor Dr. MohdAliHashim ProfessorDr. Professor Dr. LooiLaiMeng Azian Awang AzianAwang HIR Annual report 2011.indb 11 24/05/2012 9:44:45 12 High Impact Research Annual Report 2011 ProfessorDr. Professor Dr. RosnahMohd.Zain (Chairman) HIR COMMITTEE FACULTYOFDENTISTRY Associate Professor Dr. AssociateProfessorDr. NoorHayatyAbuKasim Professor Dr. ProfessorDr. NgeowYunFong ProfessorDr. Professor Dr. MohdAminJalaludin ProfessorDr. Professor Dr. EdwardTiekink Professor Dr. ProfessorDr. Mohd.RaisMustafa Secretariat,HighImpactResearchGrant ResearchManagementCentre(RMC) Level 6, Postgraduate & Research Building Building FacultyofDentistry UniversityofMalaya,50603KualaLumpur dentistry.um.edu.my/ rmc_dental@um.edu.my Intan Suhana Hamid IntanSuhanaHamid HIR Annual report 2011.indb 12 24/05/2012 9:44:48 High Impact Research Annual Report 2011 13 ProfessorDr. Professor Dr. SitiSalwahSalim (Chairman) HIR COMMITTEE FACULTY OF COMPUTER SCIENCE & INFORMATIONTECHNOLOGY Associate Professor AssociateProfessor Dr.PhangKeatKeong Associate Professor AssociateProfessor Dr.AbdullahGhani Associate Professor Dr. AssociateProfessorDr. LingTeckChaw Secretariat,HighImpactResearchGrant OfficeoftheDean FacultyofComputerScience&InformationTechnology UniversityofMalaya,50603KualaLumpur www.fsktm.um.edu.my EmeritusProfessorDr. Emeritus Professor Dr. LamSaiKit ProfessorDr. Professor Dr. OngSengHuat ProfessorDr. Professor Dr. MasjukiHajiHassan Muhamad Afiq MuhamadAfiq ZainiAlamar HIR Annual report 2011.indb 13 24/05/2012 9:44:49 14 High Impact Research Annual Report 2011 UM HIR ADVISORY COUNCIL In order to ensure the success of HIR, Tan Sri VC has appointed several distinguished scientists to be members of theUMHIRAdvisoryCouncil.Councilmemberswilladvisetheuniversityinmattersrelatedtoresearchpriorityareas, includingconductingjointresearchbetweentheirowninstitutionsandouruniversity. To date, three UM Nobel Fellows and one Distinguished Fellow have been appointed and the brief profile of each memberisprovided. NobelFellowBarryMarshall (Nobel Prize in Physiology orMedicine,2005) Nobel Fellow David Baltimore (Nobel Prize in Physiology or Medicine,1975) Prof.BarryMarshallisProfessor of Clinical Microbiology at the UniversityofWesternAustralia. His work in proving that the bacterium Helicobacter pylori is the cause of most peptic ulcers earned him and his long-term collaborator, Robin Warren, the 2005 Nobel Prize in Physiology. In honour of Prof. Marshall winning the Nobel Prize, UWA set up The Marshall Centre in 2007 to perform world-class infectious diseasesresearchanddisease surveillance. Prof. David Baltimore is currently the Robert A. Millikan Professor of Biology at the California Institute of Technology. In 1975, at the age of37,hesharedtheNobelPrizein PhysiologyorMedicinewithHoward Temin and Renato Dulbecco for their discoveries concerning the interaction between tumour viruses andthegeneticmaterialofthecell. Nobel Fellow Ryoji Noyori (Nobel Prize in Chemistry, 2001) Prof.RyojiNoyoriisPresident of RIKEN, one of Japan’s largestresearchorganizations with more than 3,000 scientists.HeisalsoProfessor intheDepartmentofChemistry and Research Center for Materials Science at Nagoya University.Hesharedthe2001 NobelPrizeinChemistrywith William S. Knowles for the study of chirally catalyzed hydrogenations. HIR Annual report 2011.indb 14 DistinguishedFellowRitaColwell Prof. Rita Colwell is Distinguished University Professor at the University of Maryland at College Park and at Johns Hopkins University Bloomberg School of PublicHealth,USA.Sheiscurrently USPresidentScienceEnvoytothe AsiaPacific.Herresearchinterests focusonglobalinfectiousdiseases andsheiscurrentlydevelopingan international network to address emerging infectious diseases and waterissues. 24/05/2012 9:44:49 High Impact Research Annual Report 2011 15 LIST OF SUCCESSFUL APPLICANTS 2011 (HIRProjects–2Years) No. HIR Annual report 2011.indb 15 Faculty Principal Investigator (PI) No. of Tier 1 ISI-Indexed Publications International Collaborations 1 FacultyofScience Prof.Dr.KamTohSeok 5 1 2 FacultyofMedicine Prof.Dr.MohdRaisMustafa 5 2 3 FacultyofScience Dr.LeeChoonWeng 2 1 4 FacultyofMedicine Prof.Dr.FongMunYik 3 1 5 FacultyofMedicine Prof.Dr.JamunaVadivelu 5 0 6 FacultyofMedicine Dr.NoraishahMydinAbdulAziz 3 2 7 FacultyofScience Dr.TeeKokKeng 5 2 8 FacultyofMedicine Prof.Dr.TanNgetHong 2 0 9 FacultyofEngineering Dr.IswadiJauhari 3 0 10 FacultyofDentistry Dr.MariamAbdullah 4 0 11 FacultyofMedicine Prof.Dr.WangChewYin 2 1 12 FacultyofMedicine Dr.FungShinYee 3 0 13 FacultyofScience Prof.Dr.HarithAhmad 3 4 14 FacultyofEngineering Dr.SuhanaMohdSaid 2 0 15 FacultyofScience Dr.ChiuWeeSiong 15 0 16 FacultyofMedicine ProfDrNorlisahMohdRamli 2 1 17 FacultyofMedicine Prof.Dr.IkramShahIsmail 2 1 18 FacultyofEngineering Assoc.Prof.Dr.MohdRafieJohan 3 1 19 Inst.ofOcean&EarthSciences Dr.LimPhaikEem 2 1 20 FacultyofEngineering Dr.ChaiHwaKian 3 4 21 FacultyofEngineering Dr.NorHafizahRamli@Sulong 2 0 22 FacultyofEngineering Dr.UbagaramJohnsonAlengaram 3 4 23 FacultyofBuiltEnvironment Prof.Dr.HamzahAbdulRahman 1 0 24 FacultyofEngineering Dr.DharmaniDevia/pMurugan 2 0 25 FacultyofMedicine Prof.Dr.WanAzmanWanAhmad 4 1 26 FacultyofEngineering Dr.SaravananPichiah 3 2 24/05/2012 9:44:49 16 High Impact Research Annual Report 2011 LIST OF SUCCESSFUL APPLICANTS 2011 (HIR-MoHEProjects–5Years) No. Faculty Principal Investigator (PI) No. of Tier 1 ISI-Indexed Publications International Collaborations 1 FacultyofMedicine Prof.Dr.AdeebaKamarulzaman 66 5 2 FacultyofMedicine Prof.Dr.SazalyAbuBakar 80 7 3 FacultyofMedicine Prof.Dr.MohdRaisMustafa 24 2 4 FacultyofMedicine Prof.Dr.TunkuKamarulZamanTunkuZainolAbidin 36 3 5 FacultyofMedicine Prof.Dr.ZahurinMohamed 35 4 6 FacultyofMedicine Prof.Dr.WongKumThong 18 9 7 FacultyofMedicine Prof.Dr.MustafaAliMohamad 24 1 8 FacultyofMedicine Prof.Dr.TanChongTin/Dr.AzlinaAhmadAnnuar 41 1 9 FacultyofMedicine Prof.Dr.FongMunYik 13 1 10 FacultyofMedicine Prof.Dr.MohamadHussainHabil 13 2 11 FacultyofMedicine Prof.Dr.MaryAnneTanJinAi 32 3 12 FacultyofMedicine Prof.Dr.HanyAriffin 80 10 13 FacultyofMedicine Prof.Dr.OnnHashim 38 NA 14 FacultyofMedicine Prof.Dr.AwangBulgibaAwangMahmud 24 5 15 FacultyofMedicine Dr.PuteriShafinazAkmarAbdulRahman 0 NA 16 FacultyofMedicine Prof.Dr.FongMunYik 70 2 17 FacultyofMedicine Prof.Dr.ChungLipYong 11 1 18 FacultyofEngineering Prof.Dr.MohdHamdiAbdShukor 29 1 19 FacultyofEngineering Prof.Ir.Dr.MohdZaminJumaat 18 4 20 FacultyofEngineering Prof.Dr.MohdAliHashim 24 2 21 FacultyofEngineering Dr.HazlieMokhlis 10 1 22 FacultyofEngineering Assoc.Prof.Dr.FatimahIbrahim 12 2 23 FacultyofEngineering Prof.Dr.T.M.IndraMahlia 15 NA 24 FacultyofEngineering Prof.Dr.MasjukiHj.Hassan 71 1 25 FacultyofEngineering Dr.AndriAndriyana 17 NA 26 FacultyofEngineering Prof.Dr.SulaimanWadiHarun 14 2 27 FacultyofEngineering Assoc.Prof.Dr.NoorAzuanAbuOsman 49 2 28 FacultyofEngineering Prof.Dr.WanMohdAshriWanDaud 34 1 29 FacultyofEngineering Assoc.Prof.Dr.MohdRafieJohan 33 NA 30 FacultyofEngineering Dr.JayaNarayanSahu 12 5 31 FacultyofEngineering Assoc.Prof.Dr.NoorAzuanAbuOsman 45 2 32 FacultyofEngineering Prof.Dr.T.M.IndraMahlia 20 NA 33 FacultyofEngineering MadamNorrimaMokhtar 10 1 34 FacultyofEngineering Prof.Dr.SaadMekhilef 9 2 35 FacultyofEngineering Dr.MohammedHarunChakrabarti 10 2 36 FacultyofEngineering Assoc.Prof.Dr.NorhayatiSoin 7 2 37 FacultyofEngineering Dr.JayaNarayanSahu 17 6 38 FacultyofEngineering Dr.HendrikSimonCornelisMetselaar 49 1 39 FacultyofEngineering Assoc.Prof.Dr.HewWooiPing 40 5 40 FacultyofEngineering Dr.MahidzalDahari 40 NA HIR Annual report 2011.indb 16 24/05/2012 9:44:49 High Impact Research Annual Report 2011 17 LIST OF SUCCESSFUL APPLICANTS 2011 (HIR-MoHEProjects–5Years) No. Faculty Principal Investigator (PI) No. of Tier 1 ISI-Indexed Publications International Collaborations 41 FacultyofScience Prof.Dr.HarithAhmad 28 3 42 FacultyofScience Prof.Dr.SriNurestriAbdMalek 150 NA 43 FacultyofScience Prof.Dr.EdwardR.T.Tiekink 150 1 44 FacultyofScience Prof.Dr.YatimahBintiAlias 25 1 45 FacultyofScience Prof.DrKamTohSeok 28 1 46 FacultyofScience Prof.Dr.SaadahAbdulRahman 45 3 47 FacultyofScience Prof.Dr.MohammadNiyazKhan 11 NA 48 FacultyofScience Assoc.Prof.Dr.KoshyPhilip 27 NA 49 FacultyofScience Prof.Dr.A.HamidA.Hadi 35 1 50 FacultyofScience Prof.Dr.KwekKuanHiang NA NA 51 FacultyofScience Prof.Dr.RauzahHashim 10 1 52 FacultyofScience Prof.Dr.EdwardR.T.Tiekink 100 1 53 FacultyofScience Prof.Dr.KurunathanRatnavelu 26 NA 54 FacultyofDentistry Assoc.Prof.Dr.NoorHayatyAbuKasim 36 1 55 FacultyofDentistry Assoc.Prof.Dr.SabriMusa 18 1 56 FacultyofDentistry Prof.Dr.ZainalAriffAbdulRahman 11 3 57 FacultyofDentistry Dr.V.RathnaDevia/pA.Vaithilingam 6 1 58 FacultyofDentistry Assoc.Prof.Dr.ChaiWenLin 8 1 59 FacultyofDentistry Prof.Dr.RosnahMohd.Zain 9 1 60 FacultyofDentistry Dr.JacobJohnChiremelChandy 3 2 61 FacultyofDentistry Prof.Dr.RosnahMohd.Zain 10 2 62 FCSIT Dr.WongKokSheik 3 2 63 FCSIT Dr.EffirulIkhwanRamlan 15 2 64 FCSIT Assoc.Prof.Dr.AbdullahBinGhani 15 3 65 FCSIT Dr.MohammedZiaurRahman 20 1 66 FCSIT Prof.Dr.SitiSalwahSalim 7 1 67 FCSIT Dr.NgLiangShing 15 3 68 FacultyofScience Dr.ChanKokGan 100 8 69 FacultyofMedicine Prof.Dr.JamunaVadivelu 150 16 70 FacultyofMedicine Prof.Dr.TunkuKamarulZamanTunkuZainal Abidin 81 6 71 FacultyofScience Assoc.Prof.Dr.RaymondOoi 60 3 72 FacultyofScience Prof.Dr.RauzahHashim 100 10 73 FacultyofMedicine Prof.Dr.YipChengHar 120 1 74 FacultyofEngineering Assoc.Prof.Dr.FaisalRafiqAdikan 70 2 75 FacultyofDentistry Dr.LawrenceChooSiewWoh 100 2 76 FacultyofMedicine EmeritusProf.Dr.LamSaiKit NA NA *FCSIT–FacultyofComputerScienceandInformationTechnology HIR Annual report 2011.indb 17 24/05/2012 9:44:49 HIR Annual report 2011.indb 18 24/05/2012 9:44:49 High Impact Research Annual Report 2011 19 RESEARCH PROPOSAL • • • • • • • HIR Annual report 2011.indb 19 HIR2years HIR-MoHE(Medicine) HIR-MoHE(Engineering) HIR-MoHE(Science) HIR-MoHE(Dentistry) HIR-MoHE(ComputerScience&InformationTechnology) HIR-MoHE(Chancellory) 24/05/2012 9:44:49 20 High Impact Research Annual Report 2011 RESEARCH PROPOSAL (HIR2Years) Project No: UM.C/625/1/HIR/050 Title: Investigating Primary Productivity in Tropical Coastal Waters Principal Investigator : Associate Professor Dr. Lee Choon Weng Faculty : Institute of Biological Sciences, Faculty of Science SummaryofResearchProposal Primaryproductionisoneofthemajorcarbonflowsintheupperwatersofmost aquaticsystems.Primaryproductionisalsothebaseofallfoodpyramids,and determinesthenumberoftrophiclevelssupportedinanecosystem.Although webetterunderstandpartsofthemarinemicrobialfoodweb,westilldonot know the amount of primary production that is grazed, and transferred to highertrophiclevels.Thiscarbontransferconstitutesthemainfoodchaini.e. phytoplanktontozooplankton,andeventuallytofish.Therefore,knowingthe amountofcarbontransferredtozooplanktonisessentialtoourunderstanding andpredictionofourfishstock.Wehaveearliershownthatonly30–40%of primaryproductionwasaccountedforbybacterialconsumption.Asbiomass ofprimaryproducersdoesnotchangesignificantlyfromoneyeartothenext, about 60 – 70% of primary production remains unaccounted. A possible avenue for the primary production is grazing by zooplankton. We will also measure the extent of phototrophic picoplankton production in our coastal waters.Comparisonwithtotalprimaryproductionwillsuggesttheimportance ofphototrophicpicoplanktoninourcoastalwaters. Objectives Methodology Todeterminetheamountofprimary production transferred to higher trophiclevels Totalprimaryproductionandgrazing potential will be measured via the Landry-Hassett dilution method. The phototrophic picoplankton productionandgrazingwillalsobe measured via the Landry-Hassett dilution method in a separate microcosmexperimentalsetup To measure the abundance and production of phototrophic picoplankton Outcome Able to constrain the carbon and energyproductionandtransferfor primaryproducers Possible High Impact Journals forPublications MicrobialEcology Applied and Microbiology Environmental MarineEcologyProgressSeries FreshwaterBiology Collaborator Assoc.Prof.Dr.IsaoKudo,Hokkaido University Allowsecosystemmodelinginthe future HIR Annual report 2011.indb 20 24/05/2012 9:44:49 High Impact Research Annual Report 2011 21 Project No: UM.C/625/1/HIR/060 Title: Antimicrobial Peptides against Multidrug Resistant Burkholderia pseudomallei and Mechanisms of Action Principal Investigator : Professor Dr. Jamuna Vadivelu Faculty : Department of Medical Microbiology, Faculty of Medicine SummaryofResearchProposal Burkholderia pseudomallei, the causative agent of melioidosis, are widely foundinthesoilandsurfacewaterthroughoutthetropicsespeciallyinSouth EastAsiaandNorthernAustralia.Currently,therearenovaccinesavailable for the treatment of Melioidosis. Antibiotic therapy is also problematic becauseB. pseudomalleiisintrinsicallyresistanttomanyantibiotics,resulting in high mortality rates of 19% in Australia and even 50% in Thailand. The spread of antibiotic-resistant bacterial infections has stimulated the need for development of new antibiotics. Antimicrobial peptides (AMPs) possess potentbroad-spectrumbactericidalactivitiesandareregardedaspromising therapeutic alternatives in the fight against resistant microorganisms. Moreover, these peptides may also affect inflammation, immune activation andwoundhealing. HIR Annual report 2011.indb 21 Objectives Methodology Outcome To identify and evaluate the efficacy of suitable synthetic or naturalantimicrobialpeptidesand peptides that will be designed based on the functional groups of effective antibiotics against B. pseudomallei as an alternate therapeutic modality. Following screening of suitable peptides that are effective against B. pseudomallei, the mechanism of action of these peptides will also bedetermined B. pseudomallei isolates will be obtained from Universiti Malaya Medical Centre (UMMC) and International Islamic University (UIA), Pahang and the sensitivity of these isolates towards commonly used antibiotics will be determined using the MIC E-test, disk diffusion and micro broth dilution methods. Resistant strainswillbeidentifiedandtested usingidentifiedsyntheticornatural antimicrobialpeptides.Thetoxicity of the selected peptides will also be evaluated using time kill studies and cytotoxicity studies. The mechanism of membrane damage caused by the selected peptides will be determined using membranepermeabilisationassay, determination of phosphate and potassium ion efflux followed by electron microscopy analysis. The antimicrobial action of these peptides will also be analysed using whole genome transcription profilingtoenableidentificationof thepossibledrugtargetsites Enable selection of antimicrobial peptides that are potent, effective and suitable as alternative therapeutics against B. pseudomalleiinfection Possible High Impact Journals forPublications PLoSPathogen InfectionandImmunity ClinicalMicrobiologyandInfection MolecularMicrobiology Collaborators Prof.Dr.NoorsaadahAbdRahman (DepartmentofChemistry,UM) 24/05/2012 9:44:49 22 High Impact Research Annual Report 2011 Project No: UM.C/625/1/HIR/062 Title: Is the Leading Edge of Neurulation an Asymmetrical Lamellipodia-Like Structure Emanating From the Surface Ectoderm and Whether This Mirrors the Human Spina Bifida Condition? Principal Investigator : Dr. Noraishah Mydin Abdul-Aziz Faculty : Department of Parasitology, Faculty of Medicine SummaryofResearchProposal PreliminarystudiesconductedbyAbdul-Azizetal.showedthatperturbation of Eph/ephrin signalling produced an enlarged posterior neuropore, multiple apoptoticcells,andfilopodial-likeprotrusionsfromtheleftsidedneuralfold (refertoappendix).Interestingly,anasymmetricallamellipodialstructurewas observed emanating from the left non-neural ectoderm. The driving force of adhesion and fusion distinctly expresses EphA2 as it branches into the lumenandreachesovertotherightnon-neuralectodermaltip.Thismayhelp explain the probability that the surface ectoderm may play a much bigger roleinneurulationandpost-neurulationthanpreviouslythought.Thesurface ectodermwhichactsastheleadingedgeofneuraltubeclosuredippinginto theluminalareaadjacenttothetipoftheneuroepithelialfoldspriortoclosure maybetheprecursoreventtopostnatalspinabifidapatientswithdimplein theepithelialskincoveringsacofneuralmatter.Thedimplemayverywellbe aconsequenceofthesinkingphenomenaseenduringadhesionandfusionof primaryneurulation(Abdul-Azizetal.2009).Thesmallmoleculeantagoniststhat willbeusedinthisstudy,4-and5-(2,5dimethyl-pyrrol-1-yl)-2-hydroxybenzoic acid, were identified by Noberini et al. (2008) to selectively inhibit ligand bindingonEphA4andEphA2receptors,allowingfordiscriminationofEphA4 andEphA2activityduringspinalneurulation.IfindeedEph/ephrinsignalingis directly involved with formation of lamellipodia- or filopodia-like protrusions to initiate adhesion and fusion, blocking of Eph/ephrin binding may disrupt formationofsolidultrastructureleadingtofailureofneuraltubeclosure. Objectives Methodology To elucidate the role of ultrastructures at the point of adhesionandfusion PreparationofRatSerum To pinpoint the basis of ephrin ligand binding which may lead to formationofmultipleultrastructures whenforwardsignallingisdisrupted WholeEmbryoCulture Preparation Solutions of Microinjection Analysisofembryos PreparationofEmbryosforScanning ElectronMicroscopy(SEM) Preparation of Embryos for Transmission Electron Microscopy (TEM) Generation double knockout of EphA2EphA4 Outcome Elucidation of the mechanism of adhesion and fusion during spinal neuraltubeclosure. Elucidationofthehumangenefor spinalneuraltubeclosure Rescueofthemousespinaldefect using a specific oil with highest content of naturally occurring linoleicacid(anewsupplementto preventneuraltubedefects) HIR Annual report 2011.indb 22 Possible High Impact Journals forPublications NatureàQ1;Impactfactor29.0 Development à Q1; Impact factor 7.194 Developmental Biology à Q1; ImpactFactorof4.379 PLoS One à Q1; Impact factor: 4.351 PLoS Genetics à Q1; Impact factor:9.532 Collaborators DrNicholasDanielEdwardGreene, Reader, University College London (UCL) Institute of Child Health, 30 Guildford Street, London WC1N 1EHUnitedKingdom Dr Catherine University Nobes, Bristol Professor Jonathan Clarke, Head, Department of Anatomy, Kings CollegeLondon Prof Aminah Abdullah, Universiti KebangsaanMalaysia 24/05/2012 9:44:49 High Impact Research Annual Report 2011 23 Project No: UM.C/625/1/HIR/066 Title: High-Resolution Molecular Epidemiology And Transmission Pattern Of Blood-Borne Viruses Commonly Found In Parenterally Infected HIV Patients Principal Investigator : Dr. Tee Kok Keng Faculty : Centre of Excellence for Research in AIDS (CERIA), Faculty of Medicine SummaryofResearchProposal In Malaysia, a total of 78,784 human immunodeficiency virus type 1 (HIV1) cases have been reported while 9,586 people have died of AIDS-related illnessesasofJune2007.Ofthese,morethan75%wereinfectedparenterally throughinjectingdruguse.InadditiontoHIV,anumberofotherhumanviruses havebeendocumentedtoshareasimilarrouteoftransmission,namelythe hepatitisCvirus(HCV)andthenewlydiscoveredhumanparvovirus4(PARV4). ChronicHCVinfectionhasbeenstronglyassociatedwithlivercancer.Asof December 2008, it was reported in Malaysia that among 5,804 drug users attending the Methadone Maintenance Treatment program in hospitals and primaryhealthcaresettings,28%areinfectedwithHCV(unpublisheddata). Among HIV-positive injecting drug users (IDUs) however the prevalence of HCV is exceptionally high at 100%, underlining the severity of HIV/HCV co-infection among this high-risk group. Biologically, HCV is classified into seven genotypes that further diverged into over 80 distinct subtypes. Such enormousgeneticcomplexityplaysacriticalroleindeterminingthestrategy andsuccessforHCVtreatment. HumanPARV4wasfirstidentifiedinanIDUwithacuteviralsyndrome.Since the discovery, PARV4 infection has been detected in a number of studies involvingIDUsinwhichitsprevalenceisexceptionallyhighamongHIVand/ orHCVinfectedpatients.CurrentunderstandingofPARV4infectionislimited, andfurtherworkisrequiredtoinvestigatethenaturalhistoryofPARV4,the timescaleforitsemergenceamongIDUs,anditsclinicalimpactonHIVand/ or HCV infected patients. In Malaysia, however, no information on PARV4 infectionhasbeenreporteddespiteover13,000newIDUs(asof2006)being detectedeveryyear. Objectives Methodology Toinvestigatetheseroprevalence, genetic complexity and possible emergence of novel HCV strains amonginjectingdrugusers(IDUs) inMalaysia Antiretroviral-naive subjects who acquired HIV-1 through injecting drug use will be recruited in the University of Malaya Medical Center and Kajang prison, Kuala Lumpur in 2011. Antibodypositive samples will be screened for HCV molecular subtypes using established PCR and highthroughput sequencing methods based on the 5’NCR-core-E1-E2p7-NS2andNS5Bgeneticregions. Phylogenetic reconstruction will be estimated for each codonaligneddatasetusingtherigorous maximum-likelihood approach implemented in PAUP* v4.0 beta and the Bayesian’s Markov chain Monte Carlo (MCMC) platform implemented in BEAST v1.4. Geneticallydistinctandstatistically robustlineageswillbedetermined. Full-length genome for potential To investigate the phylodynamics of HCV by reconstructing the spatial and temporal spread amongdruginjectionnetworks To determine the seroprevalence and genetic diversity of human parvovirus 4 (PARV4) among HIVinfected and non-HIV-infected IDUs To assess the pathogenesis of PARV4onHIVdiseaseprogression To investigate the frequency of PARV4 co-transmission with HIV and/orHCV HIR Annual report 2011.indb 23 novel HCV subtype will be sequencedbylong-fragmentPCR method For PARV4 investigations, the samesetofsubjectsrecruitedfrom UMMCandtheKajangprisonwill be used, plus approximately one hundredHIV-positivepatientswho acquired infections through nonparenteralroutes(e.g.heterosexual or homosexual risk). Categorized into two arms (parenteral vs. non-parenteral), HIV subjects will be screened for anti-PARV4 viral protein 2 (VP2) immunoglobulin G (IgG) using a newly developed indirect ELISA assay. To detect PARV4 DNA in the plasma, IgGpositive samples will be amplified by established PCR assay – with primers specific for the second open reading frame (ORF2) of 24/05/2012 9:44:50 24 High Impact Research Annual Report 2011 PARV4,homologoustothecapsid protein of other parvoviruses – and sequenced for PARV4 genotype determination. Rigorous phylodynamics analysis will be usedtodeterminethefrequencyof PARV4 co-transmission with HIV and/orHCV Outcome Serology and molecular investigations of HCV provide new insights on (a) the magnitude of HCV infections in HIV-infected IDUs, (b) the major circulating HCV genotypes in the country (c) the evolutionary trajectory and expansion of major HCV clades, and (d) the full-length genomic sequence to designate a novel HCV subtype. The first large-scale surveillance of PARV4 infections will generate essential knowledge on (a) PARV4 prevalence in HIVinfectedIDUs,(b)theclinicaleffect ofPARV4onHIVinfection,and(c) theco-transmissionofPARV4with HIV and/or HCV through injecting drugpractices Possible High Impact Journals forPublications Lancet Journal of the American Medical Association PLoSMedicine ClinicalInfectiousDiseases JournalofInfectiousDiseases Collaborators AdeebaKamarulzaman&YeatMei Lee,UniversityofMalaya,Malaysia Xueshan Xia, Kunming Institute of ScienceandTechnology,China Yi-Ming Arthur Chen, National Yang-MingUniversity,Taiwan Yutaka Takebe, National Institute ofInfectiousDiseases,Japan Project No: UM.C/625/1/HIR/051 Title: Investigation of Antivenom Therapy of Snakebites in Southeast and South Asia and Antivenomics Principal Investigator : Professor Dr. Tan Nget Hong Faculty : Department of Molecular Medicine, Faculty of Medicine SummaryofResearchProposal Snakebiteisgloballyahighlyrelevantpublichealthissue,thoughsystematically neglected by health authorities in many parts. It is a major public health concern in tropical and subtropical nations, including Malaysia. The most effectivetreatmentforsnakebiteisantivenomtherapy.Recently,development in immunodiagnosis of snakebite, new technologies of preparing polyvalent antivenoms and studies of pharmacokinetics of venom and antivenom using ELISAhavecontributedsignificantlytotheimprovementofsnakebitetreatment. Recentdevelopmentofantivenomicsandvenomicsopensupthepossibilityof in-depthstudiesofinteractionsbetweenantivenomandvenomcomponents, whichcouldcontributetothedevelopmentofhighlyeffectiveantivenom.and treatmentofsnakebites,aswellasdiscoveryofnoveltherapeuticagentsfrom snakevenoms. ResearchQuestions: 1. HIR Annual report 2011.indb 24 InMalaysia,therearesome18differentlandvenomoussnakesbut atthemoment,onlymonovalentcobraantivenomandmonovalent Malayan pit viper antivenom are available. Two new polyvalent antivenoms(hematoandneuropolyvalentantivenoms)havebeen produced by Thai Red Cross Society. The applicability of the antivenoms against venomous snakes in Southeast Asia has yet tobeevaluated.Sincelethalityassayisonlyoneofthecriteriain assessingtheeffectivenessofantivenom,itisnecessarytoevaluate the protective action of the antivenom against the cardiovascular andneuromusculareffectsofthevenoms. 24/05/2012 9:44:50 High Impact Research Annual Report 2011 2. 25 Optimization of antivenom treatment of snakebites requires knowledgeonpharmacokineticsofvenomandantivenoms.Thereis littleinformationaboutpharmacokineticsofvenomsfromSoutheast Asian(includingMalaysian)venomoussnakes.Pharmacokineticsof thenewpolyvalentantivenomshavenotbeeninvestigated. The proteome of venoms from Malaysian (and most of Southeast Asian) venomous snakes have not been investigated. The antivenomics of the monovalent or polyvalent antivenoms against Malaysian venomous snakes havealsonotbeeninvestigated. Objectives Methodology Outcome The objectives of the project are to conduct pre clinicals trials of antivenom therapy of snakebites in Malaysia, Southeast Asia and in Sri Lanka using the new polyvalent antivenoms, and to invesigate the pharmacokinetics, venomics and antivenomics of Southeast venomous snakes, for understanding of venom compositions, possible drug discovery and improvement of antivenomtreatments Preclinical trials of antivenoms:. The antivenom will be preincubated with various venoms to examine the neutralization of lethality, hemorrhagic activity, procoagulant activity and necrotic activity. In addition, the neutralization of venom cardiovascular and neuromuscular toxicities will be evaluatedusingpharmacological experiments Theprojectwillbringnewfindings in the area of benefits of the new polyvalent antivenoms in the treatment of snakebites in Southeast Asian region, and new knowledge in the area of pharmacokinetics of venom and proteome and venoms from Malaysianvenomoussnakes. Pharmacokinetics of venoms and antivenom: Both the venom antigen and antivenom antigen levelsinrabbitswillbemonitored bydoublesandwichELISA Proteome of Southeast Asian snake venoms (Venomics): A variety of approaches will be used to examine the proteome of SoutheastAsian snakevenoms, including Shotgun-LC-MS/MS), 1DE- LC-MS/MS), (GF-LC-MS/ MSand2DE-MALDITOF-MS) Antivenomics:This will be based on the immunodepletion of toxinsuponincubationofwhole venom with antivenom. Venom components that remain in the supernatantwillthenbyidentified by reverse-phase HPLC, and comparedtovenomicsresults Isolation of active compounds from venoms: These will be carried out using high performance ion exchange chromatography, reverse-phase HPLC and high performance gel permeation chromatography Potential applications include: Improvement in snakebite treatments in Malaysia and Sri Lanka,andpotentially,inSoutheast Asia; knowledge of the venomics of Malaysian venomous snakes may lead to discovery of novel drugs and biomedical tools and knowledge of the antivenomics may lead to improvement in antivenomproduction Possible High Impact Journals forPublications BiochemicalPharmacology Proteomics JPharmacologyandExperimental therapeutics Comparative Biochem Physiology,PartC and TransRoyalSocTropicalMed Collaborators Dr. Fung Shin Yee, Faculty of Medicine,UM Prof Dr. Sim Si Mui, Faculty of Medicine,UM Dr. Tan Choo Hock (MBBS) (PhD candidate), Faculty of Medicine, UM LeongPohKuan(PhDcandidate), FacultyofMedicine,UM HIR Annual report 2011.indb 25 24/05/2012 9:44:50 26 High Impact Research Annual Report 2011 Project No: UM.C/625/1/HIR/058 Title: Superplastic Effect on Diffussion of Boron/Carbon/ Ha Into Alloys Principal Investigator : Dr. Iswadi Jauhari Faculty : Department of Mechanical Engineering, Faculty of Engineering SummaryofResearchProposal Superplasticityisthephenomenonofmaterialsthatcanundergoaverylarge plasticdeformationbeforefailure.Superplasticmaterialsarecharacterizedby theirexceptionalductilitywhereamaximumelongationofabout8000%can beachieved.Owingtoitsexcellentformability,superplastichasbeenusedin theindustriestoformhardsolidsintocomplexshapepartsandcomponents. Applicationsofsuperplasticarewellknowninsuperplasticdeformation(SPD) andsuperplasticdiffusionbonding(SPDB)processes.TheSPDtechnologyis aneconomicaltechniquedevelopedwhichismainlyusedintheaerospace industry to produce components requiring complex shapes and sizes. Meanwhile,intheSPDB,thesolidstatediffusionbondinghasshownseveral advantages in achieving a good bonding strength with minimum process conditions. Basedonthesuperplasticphenomenon,wehavebeenexploringanewarea wherethesuperplasticitycouldbefurtherexploited.Fromourearlystudies, wehavemanagetoprovethatgrainboundaryslidingphenomenonobserved in the superplastic deformation plays an important role in transferring rate of atoms diffused into the substrate materials. Applying superplastic deformation, atoms such as boron and carbon can be diffused into materials like duplex stainless steel and titanium much faster than through theconventionaldiffusionmethod.Thedistributionofthediffusionprocess is more uniform and homogeneous. We found out also that the activation energyforthediffusionprocessismuchlowerthantheconventionaldiffusion processandisstrongly-dependentthestrainrateapplied.Thesuperplastic deformationnotonlypermitsatomstodiffuseintothesubstrateinaveryfast manner,italsoallowsthediffusionofthesubstrateatomsfromthesubstrate insimilarmanner. Objectives To study superplastic effects on carburizing, boronizing and HA embedmentofalloys To develop methods to apply in study1 Tomakeprototypes Methodology Carbon and boron atoms will be diffused into alloys like duplex stainless steel and titanium while HAwillbeembeddedontitanium, using superplastic deformation method. The process will be conducted in high temperature withhighvacuumdegreecondition undercompressionmode Diffusion rate of carbon and boronintothealloysanddiffusion rate of titanium into HA will be measured and the properties will becharacterizedusingXRD,EDX, FESEM,opticalmicroscope,nano andmicrohardnessindentor HIR Annual report 2011.indb 26 The optimum condition of the process will be determined based from the efficiency of the process (activationenergy) Mechanical (hardness,tensile,wear etc.)andinvivoandinvitrotesting willbeconducted Jigsanddieswillbedesignedfor prototypedevelopment Outcome Fromthestudieswehaveobtained important and useful data that would lead to the applications of superplasticity in surface engineering area where diffusion ofatomsisverycritical.Weexpect that with superplasticity, a simple andmorepracticalprocesscanbe developedmoreefficiently Possible High Impact Journals forPublications MaterialsScienceandEngineering A MaterialsChemistryandPhysics Journal of the Mechanical BehaviourofBiomedicalMaterials ActaMaterialia Biomaterials Collaborators Nil 24/05/2012 9:44:50 High Impact Research Annual Report 2011 27 Project No: UM.C/625/1/HIR/065 Title: Evaluation of Mesenchymal Stem Cells Isolated From Various Sources As An In Vitro Models For Drug Screening and Toxicity Testing Principal Investigator : Dr. Mariam Abdullah Faculty : Department of Conservative Dentistry, Faculty of Dentistry Summary of Research Proposal Despite spiraling R&D costs in discovering new drugs for therapeutic use, 90%ofleadcandidatesidentifiedbycurrentinvitrosystemsfailtobecome drugs. The currently used in vivo tests are time consuming, expensive and require a large number of animals (Hofer et al., 2004). Therefore, there is a direneedtoestablishnewerinvitrodevelopmenttoxicityassaystoreduce thenumberoftestanimalsandexpenseswithoutcompromisingthesafety of patients. Further, such in vitro models should be better suited to test a largenumberofchemicalsthantheclassicalonesemployedinvivo.Overthe lastfewyearsthefieldofpluripotentstemcellshaswitnessedastrongshift ofparadigmfromregenerativemedicinetowardsdrugscreening.Embryonic stem cell (ESC) has emerged as an attractive model in the pharmaceutical industry for in vitro screening due to their enormous potential in facilitating drugscreeningprograms(Paletal.,2009).However,scarcityofthesource andtheinvasiveproceduresrequiredtoisolateandculturethesecellshave limited their use. In this scenario, mesenchymal stem cells are considered to be an appealing source for stem cells as they are noncontroversial, readilyaccessible,hasalargedonorpoolandnoriskofdiscomfortforthe donor. Here we propose stem cells as a novel in vitro platform for toxicity assessmentofvariouscompounds,teratogens,smallmolecules,biomaterials and drugs. These novel in vitro models can predict the effect of toxins at various phases of cell cycle as well as stages of growth, development and differentiation. Moreover, these stem cell-based models would also permit simultaneousassessmentoftoxiccompoundsofthedrugsonproliferationas wellaslineagespecificdifferentiationpotential.Themainfocusoftheproject isintendedtodevelopmesenchymalstemcells(MSCs)derivedfromvarious postnatal tissues as an in-vitro model for toxicity testing of compounds sincestemcellsareknownforproliferationanddifferentiationpotentialand itwillbeoftremendousvalueindelineatingmechanismofactionofvarious compoundsatcellularandmolecularlevel. Objectives Methodology To develop mesenchymal stem cells (MSCs) as an in vitro model forcytotoxicitytesting Sample collection protocols used will be approved by the InstitutionalEthicsCommittee.The inform consent will be obtained from all human subjects that will participate in the study and the nature of the procedure and possiblediscomfortsandriskswill befullyexplained To examine the effect of conventional drugs and neutraceuticals on survival, proliferation and differentiation potential as well as retention of stemness without senescence of MSCs To explore the effect of small molecules on cell viability and functioality of MSCs with a view tofindouttheirroleinsynergizing/ antagonizingactionofMSCs Tounderstandtheimpactofdrugs on the regenerative potentiality, immuno modulatory properties andpacarineactivitiesofMSCs HIR Annual report 2011.indb 27 Stock cultures for regular maintenanceandsubculturetobe used for experiments will be kept ready Cell survival as results of druginduced cytotoxicity will be evaluated. Cell proliferation analysis will be measured using DNA synthesis as a specific marker for replication. In these assays, labeled DNA precursors (BrdU)areaddedtocellsandtheir incorporation into genomic DNA duringtheSphaseofthecellcycle is quantified following incubation and sample preparation. MSCs will be seeded in 96 well plates at a density of 1000 cells per cm2 and it will allowed to attach overnight. Culture media of interest will be added the next day.Ateachtimepoint,theculture media will be removed and cells will be washed with phosphate buffered saline (PBS), then 0.5 ml DMEM/F12 without phenolred and thiazoly blue tetrazolium bromide (Sigma) will be added to each well. The plates will be incubated for 4 hours at 37 °C. The produced MTT-formazan will be dissolved by adding 0.5 ml 2-propanol and will be agitated in the dark on an orbital shaker for an hour and the absorbance will be measured. Total RNA from cell pellets will be collected at different time points and the RNA 24/05/2012 9:44:50 28 High Impact Research Annual Report 2011 isolation will be carried out using TRIZOL reagent (invitrogen) as per the manufacturer`s protocol. Superscript II (Invitrogen) will be usedtosynthesizecDNAfollowing the manufacturer`s instructions. PCR will be performed using 2x PCRmastermix(Thermo),18sRNA will be used as the housekeeping gene control and lineage specific markerswillbechecked Outcome Collaborators To revolutionize the concept of stemcellsasaninvitromodelfor drugscreeningandtoxicity Nil Possible High Impact Journals forPublications JCellBiochem JournalofDentalResearch JournalofEndondotics Project No: UM.C/625/1/HIR/067 Title: Postoperative Vascular Events in Unrecognized Obstructive Sleep Apnea Principal Investigator : Professor Dato’ Dr. Wang Chew Yin Faculty : Department of Anaesthesiology,Faculty of Medicine SummaryofResearchProposal Thisisalargeinternationalmulticentreobservationalcohortstudytodetermine theeffectofOSA,independentofotherriskfactors,onpostoperativevascular events. 2,000 patients at moderate-to-high risk for postoperative vascular complications; who are > 45 years of age, undergoing noncardiac surgery, thatisexpectedtorequireahospitalstayofmorethan3nights,andreceiving a general or regional anesthetic will be included in the study. 4 hospitals (includingbothuniversityandnon-universityhospitals)in4countries(including Malaysia)aroundtheworldwillrecruitpatients,overa2.0yearperiod.Study personnel will evaluate patients prior to surgery, follow patients throughout theirhospitalization,andcontactpatientsat30daysaftersurgery.Allpatients willhavetroponinTmeasuredpostsurgeryandonthefirst,second,andthird daysaftersurgery. This study will inform clinicians regarding the magnitude and severity of unrecognizedOSAinthesurgicalpopulation.Moreimportantly,itwilldetermine therisksofpostoperativevasculareventsinpatientswithunrecognizedand untreatedOSA. Objectives Methodology Outcome We hypothesize that patients with unrecognized OSA have a higher rate of postoperative vascular events than those who do not haveOSA.Thespecificaimsofthe studyaretodetermine: Setting:Weproposetorecruit400 patientsfromUniversityofMalaya MedicalCentre Theprimaryoutcomeofthisstudy is postoperative vascular event within30daysaftersurgery.Itisa composite endpoint that includes any of myocardial infarction; nonfatal cardiac arrest; stroke; pulmonary embolism; congestive heart failure; new clinically significant atrial fibrillation/flutter andcardiacdeath 1. theincidenceofunrecognized OSA in patients undergoing majorsurgery 2. theassociationbetweenOSA and postoperative vascular event 3. the relationship between nocturnal hypoxia during the firstthreenightsaftersurgery andthetimetopostoperative vascularevent HIR Annual report 2011.indb 28 Measurements:Polysomnography: Overnight PSG study will be performed on the night before surgery Oximetrymonitoring:SpO2willbe monitored in all patients on the night before surgery and during the first three nights after surgery using a wristwatch-sized portable oximeter Perioperative Care: ECG will be measured preoperatively and repeatedonday1to3aftersurgery. Venous blood will be collected 6-12hoursandonthefirst3days after surgery for measuring cTnT concentration This study will inform clinicians regarding the magnitude and severity of unrecognized OSA in the surgical population. More importantly, it will determine the risks of postoperative vascular events in patients with unrecognizedanduntreatedOSA. If, as we believe it will, our study identifies the independent risk of OSA on postoperative vascular 24/05/2012 9:44:50 High Impact Research Annual Report 2011 complication, this will lead to a change in perioperative medicine worldwide. Specifically, it will facilitate surgeons and patients in decision-making and will guide perioperative patient management. For instance, we willbebetterinformedaswhether surgery needs to be delayed for potentialpreoperativeoptimization (e.g. weight reduction, insertion of oral appliances and initiation of nocturnal continuous positive airwayspressure) Possible High Impact Journals forPublications Anaesthesiology AnaesthesiaandAnalgesia BritishJournalofAnaesthesia Chest Circulation 29 Collaborators Professor Frances Chung, UniversityToronto,Canada ProfessorMatthewTakVaiCHAN, ChineseUniversityHongKong Dr Edwin Seet Chuen Ping, AlexandraHospital,Singapore Project No: UM.C/625/1/HIR/068 Title: Genomic Analysis and Biomedical Studies of Tiger’s Milk Mushroom “Cendawan Susu Rimau” (Lignosus rhinocerus) Principal Investigator : Dr. Fung Shin Yee Faculty : Department of Molecular Medicine, Faculty of Medicine SummaryofResearchProposal Lignosusrhinocerus(Tiger’sMilkmushroom,orlocalMalayname“cendawan susu rimau (harimau)”) is one of the most important traditional medicinal mushroomsfoundinMalaysia.Thelocalcommunitieshavebeenusingthis mushroom for more than 500 years to treat asthma, fever, cough, cancer, foodpoisoning,woundhealingandasahealthtonictoimproveimmunityand maintaingeneralhealth(ChangandLee,2004).Althoughtheethnobotanical uses of L. rhinocerus are well recognized, scientific information on its pharmacologicalactivitiesisscarce.Themainconstraintwasduetolimited supply of L. rhinocerus as it can only be found in the jungle by “luck”. However,recentlyTanetal(2009)hassuccessfullycultivatedthemushroom inthelaboratory(Tan,2009)andthishasmadeitpossibletoobtainalarge supply of the mushroom, making it possible to investigate the mushroom’s bio-pharmacological properties and mode of action. This project aims to investigatethebiopharmacologicalpropertiesofTiger’sMilkmushroomand exploreitsutilizationasnutraceuticals,aswellasidentificationofitsactive ingredientsthatmayleadtodrugdiscovery. Objectives Methodology To sequence the genome of Lignosus rhinocerus and bioinformatic analysis of the gene data PartI:Genomicstudy:toobtain the genome DNA sequence of the Tiger’s Milk mushroom. This will be carried out by obtaining sufficient quantity of pure intact genomic DNA of Lignosus rhinocerus, constructing shortinsert library, evaluation of heterogenous sequences and followed by genome assembly and bioinformatics analysis. Our partnerinthegenomesequencing is BGI from Shenzhen, People RepublicofChina To establish the safety of the mushroom by conducting subacutetoxicitystudies Toinvestigatetheanti-cancerand tonicpropertiesofthemushroom PartII:Subacutetoxicitystudies: The doses will be selected according to OECD Guidelines No.407 (OECD, 1995). Groups of five male and female Sprague HIR Annual report 2011.indb 29 Dawley(SD)ratswillbegavagefed for28days: Attheendofthetreatmentperiod (Day 28), rats will be fasted for 18 hours. On day 29, blood samples will be withdrawn using cardiac puncture. Haematological examination,prothrombintimeand biochemicaltestwillbeperformed (Dufouret al.,2003) Afterbloodcollection,vitalorgans such as liver, spleen, heart, lungs and kidneys will be removed and preserved in 10% buffered formalin. These organs will then be embedded in paraffin and the tissue slices will be stained with hematoxylin and eosin. 24/05/2012 9:44:50 30 High Impact Research Annual Report 2011 Light microscopic examination of multiple tissue sections from eachorganwillbeperformedinall groups. PartIII: Anti cancer activity Determination of anti-cancer activitywillbedoneusingvarious cancer cell lines. Its mechanism will be investigated using microarray and validated by real time PCR (Fung et al, 2009), TUNNEL assay and proteomic approach. The determination of cytotoxiceffectofthemushroom on normal cell lines will also be ascertained Tonic activity ICR mice will be orally administered with Tiger’s Milk mushroom powder. At the end of the treatment, measurement oftheforcedswimmingcapacity and the analysis of blood biochemical parameters such as the levels of plasma triglyceride, glucose, lactate and ammonia will be examined. Immediately after the blood collection, liver andgastrocnemiusmusclewillbe quickly dissected out and frozen in liquid nitrogen until analysis for glycogen content using the glucoseoxidasemethod(Junget al.,2004) Outcome Understanding the mode of action of Tiger Milk mushroom as phytomedicine. Establish food safety and anti-cancer ; tonic propertiesofthemushroom Possible High Impact Journals forPublications International Journal of BiochemistryandCellBiology eCAM FoodChemistry,I JournalofEthanopharmacology FungalGeneticsandBiology Collaborators ProfDr.TanNgetHong,Department of Molecular Medicine, Faculty of Medicine,UniversityofMalaya LignoBiotechSdnBhd Project No: UM.C/625/1/HIR/071 Title: Ultrafast Laser Nanoprocessing of Large Area Plasmonicand Metamaterials: Design, Fabrication And Characterization Principal Investigator : Professor Dr. Harith Ahmad Faculty : Department of Physics, Faculty of Science SummaryofResearchProposal Thelastdecadesawtheestablishmentofanewfieldinphotonicsresearch. Itinvolvesthefabricationofmaterialswithelectromagneticpropertiesthatdo notexistnaturally.Theengineeredmaterialsormetamaterialsenablecontrol of a materials electromagnetic properties, namely the electrical permitivity, e and magnetic permeability, m for the realization of many unconventional applications including negative refractive index materials, super lens, subwavelengthimaging,cloaking,etc. The building block of metamaterial consist of thin metal resonator cavities with sub-wavelength dimensions called cell, arranged periodically on a dielectricorsemiconductorsubstrate.Inthecaseofphotonicmetamaterials, itrequiresfabricationofperiodicnano-sturcturesin2-Dandultimately3-D. This requirement is probing the limits of E-beam and X-ray lithography in nano-structurepatterning. Recently,directlaserwritingusingultrafastlaserpulseshasbeendemonstrated to be an effective tools for nano-structure processing due to its non-linear interactionwithmatterandlocalizedmaterialmodificationwithminimaleffect on adjacent structures. Feature size as small as 20nm has been fabricated usingultrafastnanomachining.Paralleldefinitionofperiodicstructuresisalso possibleusingdirectlaserwriting.Theflexibilityofdirectlaserwritingandthe nano-machiningcapabilityofultrafastlaserhasmadeitapromisingtechnology inthefabricationofphotonicsmetamaterials. HIR Annual report 2011.indb 30 24/05/2012 9:44:50 High Impact Research Annual Report 2011 Objectives Methodology To acquire understanding in the physics and fabrication methods of photonics metamaterial. To design conventional and new metamaterials. To fabricate large area photonics and terahertz plasmonics and metamaterials usingultrafastlaserandtodevelop a characterization system for the measurement of photonics metamaterials The physics and principles of surface plasmon polaritons and photonics metamaterials is first acquired. Design and simulation ofdifferentarrangementofunitcell andunitcellprofileswillbecarried out.Laserdirectwritingsystemwill besetupwithultra-violetaswellas ultrafastlaseraslasersource.The optimumdesignwillbetransferred to the fabrication process and the fabricated metamaterials. A characterization system will be setup and the characteristics of fabricated materials will be measuredusingthesystem 31 Applicationsanddevicesbasedon photonicsmetamaterials Possible High Impact Journals forPublications NaturePhotonics OpticsExpress OpticsLetters AppliedPhysicsLetters IEEEPhotonicsTechnologyLetters Collaborators HongMingHui,NationalUniversity ofSingapore,Singapore Outcome Knowledge and facility to design, fabricate and characterize photonicsmetamaterials Project No: UM.C/625/1/HIR/077 Title: Characterisation of Dielectric and Electro-Optic Parameters of Novel Nematic and Blue Phase Liquid Crystals Principal Investigator : Dr. Suhana Mohd Said Faculty : Department of Electrical Engineering, Faculty of Engineering SummaryofResearchProposal Blue phase liquid crystals are an interesting liquid crystal phase, since they are highly ordered and indicate potential for fast switching, easily manufactureddisplays.However,itcurrentlyhasthedisadvantageofhaving averynarrowwindowofexistence,intherangeof1-2°C.Afamilyofofliquid crystalsbasedonanewseriesofSchiffbaseesters,hasbeensynthesised by the Liquid Crystal group in USM since 2009, which have demonstrated the nematicandbluephases. Whilst fundamentalcharacterizationofthese compounds,as phasetransition,temperaturesandmorphologicalstructure havebeeninvestigated,littleelseisknownaboutthesematerials’properties. Thisparticularresearchprojectwilltacklethecomprehensivecharacterization ofnematicandbluephaseliquidcrystalssynthesizedinUSM.Theoutcome ofthisprojectisaimedatabetterfundamentalunderstandingofthephysical parameters of these liquid crystal series, which will lead to proposed applicationssuchaswirelessdevices,electro-opticswitchesandlasers. Objectives To characterise the dielectric parameters of nematic and blue phaseliquidcrystals To characterise the elastic constantsofthenematicandblue phaseliquidcrystals To simulate the nematic and blue HIR Annual report 2011.indb 31 Methodology phase liquid crystal structure and dynamics Tocorrelatebetweenexperimental and simulation results in order to yield nematic and blue phase liquid crystal parameter values – dielectric constants, elastic constantsandviscosity Continuum modelling will be used to predict the nematic and blue phase liquid crystal structure and dynamics. The reorientation dynamics of the liquidcrystalmaterialinanelectric field will be of fundamental interest. Continuum modelling 24/05/2012 9:44:50 32 High Impact Research Annual Report 2011 for nematic liquid crystals will be executed first, followed by blue phase liquid crystals. Dielectric characterisation of the liquid crystalshallbecarriedoutusing an impedanceanalyser. Accurate temperaturecontrolofthematerial in order to maintain it within the nematic and blue phase liquid crystal phase shall be maintained usingahotstageandcontroller. Theuseofahostageandcontroller isessential,asthephasetransition temperatures need to be very precise and sometimes have a verynarrowwindow.Forexample, the phase transition temperature forthebluephasemixture,TCB(5) isasfollows: Cr à SmC* à SmA à N* àBluePhaseà I 161.7 190 221.7 226.9 226.9 Electro-opticcharacterisationof a blue phase liquid crystal shall be carried out through observation of the electro-optic response of the cell which is switched by an electric field.Simulation of the liquid crystal structure dynamics is essential to complement the experimental results. Fitting between the experimental and simulation results will ultimately yield the parameter values of dielectric constants, elastic constantsandviscosity Possible High Impact Journals forPublications Outcome Collaborators Fundamental characterisation of material parameters of locally synthesised nematic and blue phase liquid crystals. An understanding of the material parameters will provide an indication of the suitable engineering applications. Apart from conventional display applications, a very recent and interesting application for liquid crystals will be for wireless devices,suchastunableantennas andadaptivereflectarrays Professor Yeap Guan Yeow (Universiti Sains Malaysia, Malaysia) PhysicalReviewE JournalofAppliedPhysics EuropeanPhysicalJournalE Photonics and Nanostructures – FundamentalsandApplications Dr Mohd Rafie Johan (Universiti Malaya,Malaysia) Project No: UM.C/625/1/HIR/079 Title: Fundamental Study on the Novel Magnetic Nanophotocatalyst (Zinc Oxide/Iron Oxide) for Water Splitting Process Towards the Development of A Green, Cost-effective and Sustainable Hydrogen Gas Production System Principal Investigator : Dr. Chiu Wee Siong Faculty : Department of Physics, Faculty of Science SummaryofResearchProposal: There are substantial research efforts devoted to adopt hydrogen gas as a green,renewableandsustainableenergyduetoitslowgreengasesemission. Nevertheless, the conventional industrial process to produce hydrogen gas consumesahugeamountoffossilfuels,whichinturnresultsinalargequantity of green gases emissions. Recently, hydrogen production via magnetized photocatalytic-mediatedwatersplittingprocessseemsparticularlypromising. Thistechniqueonlyexploitsradiationenergyastheprecursortoinducewater splittingprocess. Furthermore,theuniquemagneticfeaturealsofacilitateslowcostrecoveryof theactivematerialsforsubsequentusage. However, eventhough there are many research efforts to improve the photocatalyticefficiencyofsuchnanocompositematerialbydifferentsynthetic routes, fundamental understanding on its charge carrier properties is still very limited. Effects of lattice disruption/mismatch due to the incorporation ofmagneticparticlesintophotocatalystmaterialontheexcitonsgeneration, HIR Annual report 2011.indb 32 24/05/2012 9:44:50 High Impact Research Annual Report 2011 33 diffusionandrecombinationarestillambiguous.Sincephotonenergyserves astheprecursortoinducethewatersplittingprocess,chargecarrierdynamic is the most crucial property that will affect the photocatalytic efficiency. Therefore,currentresearchworkisdevotedtoestablishasoundfundamental understanding on the charge carrier property of the novel ZnO/Fe3O4 nanomaterialsbyusingtheopticalabsorptionspectroscopy. Objectives Methodology Outcome Tosynthesizeandcharacterizethe physicalandchemicalpropertiesof zincoxide/ironoxide(ZnO/Fe3O4) hybrid core-shell nanocomposites materials using a series of advanced analytical techniques (XRD,TEM,XPS,VSM). The efficiency of the water splittingprocesswillbeevaluated on the own-synthesized Fe3O4/ ZnO core/shell nanocomposites, whicharepreparedthroughseedmediatedgrowapproachbyusing organometallic synthetic route. The Fe3O4 will be synthesized by thermal pyrolysis of iron oleate precursorandwillbeusedforthe overgrowofalayerofZnOcrystals. Various analytical techniques will be used to characterize the structural and properties of this nanocomposite. The photoinduced spectroscopic study and time-resolved absorption measurement will be conducted to evaluate the charge carrier dynamicsoftheexciton. A comprehensive new theoretical description (qualitatively and quantitatively) on the charge carrier dynamic of the magnetic nanophotocatalyst material (ZnO/ Fe3O4)canbeestablished To verify the effectiveness of the ZnO/Fe3O4 hybrid nanocomposites as efficient photocatalyst material in water splittingforhydrogenproduction. To identify and optimize the photocatalytic capabilities of the as-prepared and regenerated nanophotocatalyst material against water disassociation rate andredoxmechanism. To investigate the charge carrier dynamic of the as-synthesized nanocomposite materials under theilluminationofelectromagnetic radiation To determine and optimize the water dissociation efficiency during the hydrogen evolution process in correlation to the intrinsic properties of the ZnO/ Fe3O4nanocompositematerials Meanwhile,theperformanceofthe nanocompositesintheproduction ofhydrogengasviawatersplitting reactionwillbeinvestigatedusing thegaschromatographytechnique. Finally,thecorrelationbetweenthe charge carrier dynamics with the efficiency in hydrogen production willbestudied Possible High Impact Journals forPublications ACS Nano (Publisher: American ChemicalSociety),IF=7.493 Chemistry of Materials (Publisher: AmericanChemicalSociety),IF= 5.368 Journal of Physical Chemistry C (Publisher: American Chemical Society),IF=4.224 Nanotechnology (Publisher: InstituteofPhysics,UK),IF=3.137 Chemical Engineering Journal (Publisher:Elsevier),IF=2.816 Collaborators Prof. Datin Dr. Saadah Abdul Rahman(UniversitiMalaya) Prof. Dr. Shahidan b. Radiman (UniversitiKebangsaanMalaysia) AssociateProf.Dr.KhiewPoiSim (UniversityofNottinghamMalaysia Campus) Associate Prof. Dr. Muhammad Azmi Abd. Hamid (Universiti KebangsaanMalaysia) Dr. Chia Chin Hua (Universiti KebangsaanMalaysia) HIR Annual report 2011.indb 33 24/05/2012 9:44:50 34 High Impact Research Annual Report 2011 Project No: UM.C/625/1/HIR/081 Title: Evaluation of the Use of Chemical Shift Gradient Echo Sequences in 3T MRI in the Detection of H-MRS Visible Lipids and the Grading of Gliomas Principal Investigator : Professor Dr. Norlisah Mohd Ramli Faculty : Department of Biomedic Imaging, Faculty of Medicine SummaryofResearchProposal Preoperativegradingofgliomasisnecessaryasithelpsinbettertreatment planning and management. Non invasive detection of lipid is particularly importantinreachingthediagnosisaswellasingradingthetumor.Presence oflipidpeakinaggressiveintracranialtumorshasbeenreportedwidelyusing MRspectroscopy. MRspectroscopyhowever,hasdifficultyindifferentiatinglactatefromlipids astheirspectrallocationsoverlapi.e.theyarefrequentlyevaluatedinunison. Furthermorethismethodrequireslongerimagingtimeandhaslimitationsdue toartefactsformedbyadjacentbones.Itcanonlybeeffectivelycarriedout inmagnetsoffieldstrengthof1Tandabove;andrequiresspecialsoftware. Objectives This study aims to assess the usefulness of MR chemical shift gradient echo sequences in combination with or in place of established MR spectroscopy to firstly assess the lipid content of gliomas and secondly to help determine the grade of a lesion. Thisstudywillbecarriedoutusing 3TeslaMRI.Aschemicalshiftwill increase with an increase in field strength(itdoublesinmovingfrom 1.5Tto3T),itmaybebeneficialin enhancingtheusefulnessofthein- andopposedphasechemicalshift gradientsequence Methodology This is a cross sectional study of patient with glioma. Clinical examination will be done by neurosurgeons. Informed consent will be obtained from all the subjects/guardians before the study.Patient will undergo MR imaging at 3Tesla. Standard sequences for intracranial tumor (multiplanar T1W pre and post gadolinium, T2W, FLAIR, DWI) as well as MR spectroscopy will be performed. Another sequence, using chemical shift GRE technique will be added and will be done before contrast is given. Bothopposed-phaseandin-phase FLASHimagingwillbeperformed. The ROI will be determined so as HIR Annual report 2011.indb 34 it corresponds with SVS chosen in MRS. The assessment of the lesions in MR images will be done by a radiologist. He/she will be blinded to the eventual histology grade of the tumor. The assessment will also include calculation of the percentage variation in signal intensity of the ROI between the opposed-phase andin-phaseFLASHimaging Sample of the lesion will be obtained by stereotactic biopsy, open biopsy or craniotomy as according to the decision made by the neurosurgeon during their management of the patient. Histological grading and analysis forthepresenceandquantification ofthelipidcomponentwillbedone byasinglepathologist.Gliomasof different histologic types will be graded II to IV, according to the degree of malignancy. Grade II gliomas will be taken together as low-grade, while grade III and IV willbetakenashigh-gradegliomas Outcome Chemical shift gradient echo sequence will be helpful in the diagnosis and grading of the glioma, thus may avoid unnecessary biopsy and helps in better preoperative treatment planningandmanagement Possible High Impact Journals forPublications Radiography(ISI-CitedPublication) Neurology Publication) Asia (ISI-Cited AmericanJournalofNeuroradiology Collaborators Biomedical Imaging Department, University of Malaya Medical Centre,KualaLumpur Pathology Department, Universiti of Malaya Medical Centre, Kuala Lumpur Surgical Department, University of Malaya Medical Centre, Kuala Lumpur 24/05/2012 9:44:50 High Impact Research Annual Report 2011 35 Project No: UM.C/625/1/HIR/085 Title: Role of G-Proteins In Diabetic Retinopathy: Beyond Glucose Induced Microvascular Disease Principal Investigator: Professor Dato’ Dr. Ikram Shah Ismail Faculty : Department of Medicine, Faculty of Medicine SummaryofResearchProposal Thisprojectaimstoidentifyß-AdrenergicreceptorsandAdenosinereceptors subtypes in Bovine retinal endothelial cells and rat Muller cells and then to investigate their potential role in inducing complications that are found in diabeticretinopathy.Thiswillbedonebyfirstlyinvestigatingtheireffectson the thickness of the basement membrane and pericyte loss using electron microscopy.Wethenwilldeterminetheroleofthereceptorsonthesympathetic neurotransmission in diabetic retinopathy by measuring the induction of iNOS. To determine if they affect the regulation of inflammatory cytokines, they will be measured at various times in a hyperglycemic environment. Followingthattheeffectofthesereceptorsonapoptosisthroughsympathetic neurotransmission will be investigated as well as the signaling pathways involved in inducing proliferation, apoptosis and inflammation. These will thenbeverifiedbytheexpressionofthegenesinvolvedinpericyteloss,cell proliferation,apoptosisandinflammation. Methodology Both cells will be cultured in low and high glucose media. These cell will be treated with various agonistsandantagonists.Thecells willbecollectedat5differenttime points (1, 3, 6, 18 and 24 hours). The collected cells will be used to identify the signaling pathway usingWesternBlotanalysis,ELISA assays, Gene expression using RT-PCR,ElectronMicroscopyand TUNELassay Outcome Possible High Impact Journals forPublications Diabetes DiabetesCare Diabetologia Collaborators Professor Dr. Richard Prince, University of Western Australia, Australia Dr.AstridLimb,UniversityCollege ofLondon(UCL),London New finding for treatments of diabeticretinopathy HIR Annual report 2011.indb 35 24/05/2012 9:44:50 36 High Impact Research Annual Report 2011 Project No: UM.C/625/1/HIR/086 Title: Study of the Symmetry and Optical Anisotropy in CdSe/ZnSe Quantum Dots Nanomaterials Principal Investigator : Associate Professor Dr. Mohd Rafie Johan Faculty : Department of Mechanical Engineering, Faculty of Engineering SummaryofResearchProposal Semiconductor quantum dots (QDs) have been attracting immense interest overthelastdecadefrombothbasicandapplications.Thematerialsystem of choice for the investigations performed in the frame of this research is self-assembled CdSe/ZnSe QDs. The reasons of this choice are twofold. Firstly,CdSe/ZnSeQDscanbegrownwithexcellentopticalqualitywhichis aprerequisiteforopticalstudies.Secondly,isduetothepolarnatureofII-VI compound semiconductors. For the purposes of the proposed work, QDs emergingfrominverseMichellegrowthwillbestudied. Objectives Methodology Outcome By using inverse Michelle technique, we would like to synthesize self-assembled CdSe/ ZnSeQDs.Variouscharacterization methods are used such as XRD, TEM, SEM, FTIR, PL, Raman Scattering etc. to characterize the optical, thermal and structural properties of CdSe/ZnSe QDs. Last but not least we also want to investigate the symmetry and optical anisotropy in CdSe/ZnSe QDs CdSe/ZnSe QDs were prepared usingZnAcetate,CdOandSeas precursors. Other chemicals also usedinthismethodassurfactants which are paraffin oil and oleic acid. From the mixing to produce the CdSe/ZnSe QDs, there are several times divided to study the growth of QDs which are 0 (intermediate),0.5,1,5,16,46and 90 minutes. By centrifugation, the precipitatecanbeisolatedfromthe solvents and unreacted reagents. Then after the sample dries, it canbecharacterizedtostudythe symmetry and optical anisotropy CdSe/ZnSeQDsnanomaterials Better understanding to characterize the QDs nanomaterials by using various characterizationmethods.Besides we can also study the symmetry and optical anisotropy are the application of CdSe/ZnSe QDs nanomaterials Possible High Impact Journals forPublications PhysicalReviewLetters Collaborators Profesor Sheikh Akhbar, Ohio StateUniversity,US Project No: UM.C/625/1/HIR/088 Title: Molecular Phylogenetics and Systematics of Crustose Brown Algae Principal Investigator : Dr. Lim Phaik Eem Faculty : Institute of Biological Sciences, Faculty of Science SummaryofResearchProposal Despitedetailedstudiesbeingdoneoncrustosebrownalgaesincethe1800s, thereisnotmuchstudyconductedontheminMalaysia.Priorto2007,thereis nostudyonthecrustosebrownalgaeinMalaysia.Thefirstreportofitskind in Malaysia is on two species namely: Neoralfsia expansa and Mesospora schmidtii (Lim et al., 2008). Based on these authors’ preliminary survey at various coastal areas in Malaysia, the crustose brown seaweeds are found togrowabundantly.Hencethereisaneedtoconductmorestudiesonthese algaeinMalaysia.AgenusthatdeservesourattentionistheMesospora,first described by Weber-van Bosse (1911) on the basis of materials collected fromseverallocalitiesinIndonesia.Algaeofthisgenusareamongthemost prevalentinourregionascomparedtoothercrustosebrownalgaesuchas Ralfsia. HIR Annual report 2011.indb 36 24/05/2012 9:44:51 High Impact Research Annual Report 2011 Objectives Methodology Outcome This project aims to collect and identify crustose brown algae fromvariouslocalitiesinMalaysia, Indonesia and Japan based on morphological features and reproductive organs. Further confirmation of the identity of crustose brown algae and examination of their taxonomic positionatthefamilialandordinal level can be accomplished by exploiting the use of molecular markers of chloroplast origin (rbcL) and mitochondrial-based marker (cox1). In addition to that, we are keen to determine the species number of Mesospora, commonly found in warmer waters, in this region and to distinguish Mesospora schmidtii sensu Weber-van Bosse and Mesospora schmidtii sensuTanaka & Chihara by studying specimens ofMesosporafromitstypelocality inIndonesiaandJapan Brown algal crusts will be collected from several localities in Malaysia, Indonesia and Japan. These rocks are first air-dried and later desiccated in silica gel and maintained at ambient temperature. For morphological observations, light microscopical examinations will be done on squash preparations which are then mounted in corn syrup on glass slides. As for the molecular studies, totalgenomicDNAwillbe extractedbygrinding30-40mgof thethalliinliquidnitrogenfollowed by the use of DNeasy Plant Mini Kit (Qiagen, Hilden, Germany). The isolated DNA will act as a DNA template in a polymerase chainreaction(PCR)usingvarious markers from two genomes: plastid-encoded marker (rbcL and etc.) and mitochondrial encoded marker (cox1 and etc.). The resulting PCR products will then undergo purification, cycle sequencing and finally DNA sequencing. The DNA sequences will then be analyzed and phylogenetic trees will be inferred using maximum parsimony (MP), maximum likelihood (ML) and Bayesianinferencemethods Unveil new species and diversity of crustose brown algae with particularinterestonMesospora in thisregion 37 Possible High Impact Journals forPublications Phycologia JournalofPhycology MarineBiology MolecularEcology SystematicBiology Collaborators Prof. Phang Siew Moi, Institute of Biological Sciences & Institute of Ocean and Earth Sciences, UniversityofMalaya Prof. Hiroshi Kawai, Kobe University Research Center for InlandSeas,Japan Poong Sze Wan (PhD candidate), Institute of Biological Sciences, UniversityofMalaya Project No: UM.C/625/1/HIR/089 Title: Advanced Technique for Scanning and Visualization of Structural Concrete Interior: Study on Feasibility of Various Elastic Wave Properties for Tomographic Reconstruction Principal Investigator : Dr. Chai Hwa Kian Faculty : Department of Civil Engineering, Faculty of Engineering SummaryofResearchProposal This study is primarily an attempt to understand the behavior of elastic wave propagating in concrete. The various wave properties generated fromatransientsourceisassessedfortheirvariationswhenpropagatingin concretewithdifferenttypesofirregularities.Thewavepropertiesthatexhibit quantifiablechangesaretobeutilizedasdatafortomographyreconstruction for visualization and characterization of concrete interior. The tomography technique,whichcanbebasedononeormorewaveproperties,isdeveloped withformulationofcomputeralgorithmsandinstrumentationofmeasurement that accommodate different conditions of measurement. The outcome of thisstudyshallhelpenhanceorcomplementthecurrentlyavailableconcrete scanning and evaluation techniques, which are found to still possess limitations pertaining to sensitivity and reliability attributed to difficulties in dataacquisition,extractionandinterpretation. HIR Annual report 2011.indb 37 24/05/2012 9:44:51 38 High Impact Research Annual Report 2011 Objectives Methodology Outcome First we examine and analyze, through numerical modeling and simulation as well as laboratory experiments the change in properties of transient elastic waveswhenimpingedondifferent types of anomalies/ defects in concrete. This is to identify promisingwavepropertiesforuse as observed data in tomographic reconstruction technique. The attemptalsohelpstodeterminethe practicabilityofcombiningmultiple types of observe data to improve thecreditabilityandconsistencyof theassessmentmethodingeneral. The next objective is to develop suitable computer algorithms for tomographic reconstruction using the selected wave properties, followed by instrumentation of a prototype measurement system and establishment of signal acquisition/ processing methodology that provides flexibility under different on-site measurementrequirements Propagation of transient elastic waves in concrete models with different types of anomalies/ defects is simulated numerically to examine and analyze the variation of wave properties in association with different intrinsic and measurement conditions. The analytical work also facilitate examination for changes in measurementdataduetodifferent material properties, structure geometry, wave properties, mesh discretization as well as sensor types and arrangements. Computer algorithm catered for tomographic reconstruction process of respective wave propertiesofinterestaredeveloped through programming practices. Thealgorithmsaretobetestedand modifiedaccordinglyforaccuracy and consistency. Experimental measurements are to be carried out using laboratory concrete specimens,ofwhichtheoutcome shallprovidefurtherunderstanding ontheunderlyingdifferencesinthe tomography output in association with various combinations of measurement configurations and wave properties. Besides, the experimental findings are to be utilized for conditioning and refinement of modeling and simulationwork Understand wave propagation behavior under different inherent conditions, including type and size of defects and properties of concrete. Identify promising wave properties for quantification and characterization of interior concrete defect for development of enhanced tomography measurementtechniques. Establish through instrumentation and program development, enhanced tomography measurement techniques for complementing or upgrading the currently available scanning and evaluationtechniquesforconcrete structures Possible High Impact Journals forPublications NDT&EInternational Structural Health and Monitoring: AninternationalJournal ACIMaterialsJournal EngineeringStructures Collaborators TomokiShiotani(KyotoUniversity) Yoshikazu University) Kobayashi (Nihon Ubagaram Johnson Alengaram (UniversityofMalaya) DimitriousGAggelis(Universityof Ioannina) Shohei Momoki (Tobishima Corporation Research Institute of Technology) HIR Annual report 2011.indb 38 24/05/2012 9:44:51 High Impact Research Annual Report 2011 39 Project No: UM.C/625/1/HIR/090 Title: Development of novel intumescent fire protective coating with Chicken Eggshell (CES) as bio-filler Principal Investigator : Dr. Nor Hafizah Ramli @ Sulong Faculty : Department of Civil Engineering, Faculty of Engineering SummaryofResearchProposal Structuralsteellosesmorethan60%ofitsyieldstrengthwhenitstemperature exceeds 500°C. The protection of steels against fire is widely used in the offshoreindustryandincreasinglysoforonshoreapplications.Aworldwide death toll of more than 322000 per year is due to incompetence in fire protection. Indeed, prevention of the structural collapse of the building is paramount to ensure the safe evacuation of people from the building, and is a prime requirement of building regulations in many countries. This research is to develop intumescent fire protective coating using industrial by-product i.e. ChickenEggshell(CES)asbio-fillerthatreduceproductioncostandyetfulfills thehighperformancerequirementforeffectivefireprotection. Asyet,thereisalackofextensiveresearchinthefieldofintumescentcoatings and awareness of its ability in containment of fires in Malaysia. It provides aninsulatingbarrieragainstfire,slowingthespreadofflames,allowingsteel componentstomaintaintheirstructuralintegrityforalongerperiodandgiving vitaltimeforevacuation.Thecoatingwillbecharacterizedthroughaseriesof fireandmechanicaltests.Optimizedintumescentcoatingformulationswillbe obtainedandevaluated. Objectives Methodology Outcome The objective of this research is to design and develop a highly efficient intumescent coating, which not only has the advantage of good fire protection performance, but also show great anticorrosion and mechanical properties. The influences of the binders,fillersandflameretardant additives on the fire protection, anticorrosion and mechanical properties of intumescent coating willbeanalyzedandevaluated The main focus of this research is to formulate and optimize the intumescent coating formulations. The formulations will be mixed usingahigh-speeddispersemixer. The mixture is dried until films are formed. The films are tested withDSC,TGA,UL94,XRD,XRF, FTIR and LOI to characterize the physical and chemical properties of the intumescent coating. The formulations will be applied onto steelplatesfortheBunsenburner test and small scale furnace test in order to investigate the fire protection performance of the coating. Besides that, the morphologies of the intumescent coatings will be observed using theFESEM.Thebondingstrength, bending resistance and freezethaw test of the coating will be determined using the Instron testing machine and freezer, respectively. Ultimately, the best coatingformulationwillbeapplied on full scale beam-column and its behavior evaluated under the furnacetestfollowingthestandard ISO834time-temperaturecurve Formulate a highly efficient intumescent fire protective coating formulation to protect steel structures from extensive fire damage, while at the same time offers additional benefits to the coated substrates including water resistance and corrosion protection Toward a better understanding of their mechanism of action, fire protection and anti-corrosion performanceaswellasmechanical properties Possible High Impact Journals forPublications PolymerDegradationandStability SurfaceandCoatingsTechnology MaterialsLetters ProgressinOrganicCoatings FireSafetyJournal Collaborators Professor Michael Chew Yit Lin, National University of Singapore, Singapore Associate Prof. Faiz Ahmad, UniversityTechnologyPETRONAS, Malaysia HIR Annual report 2011.indb 39 24/05/2012 9:44:51 40 High Impact Research Annual Report 2011 Project No: UM.C/625/1/HIR/093 Title: Synthesis of Novel Geopolymer Oil Palm Shell Lightweight Concrete Principal Investigator : Dr. U. Johnson Alengaram Faculty : Department of Civil Engineering, Faculty of Engineering SummaryofResearchProposal Depletionofnaturalresourcesfashionedanimportantphraseinthehistory of mankind called “sustainable development”. And in practice/research/ teaching, the significance of this phrase is often debated and emphasized in many ways. In the proposed research, we intend to achieve sustainable concretethroughtheuseoflocallyavailablewastematerials,namelyoilpalm shell(OPS)andflyash(FA);further,thisresearchisintendedtoreplacethe conventional100%naturalcoarseaggregateandcementwithOPSandFA, respectively. Thus, this research is expected to create next generation of lightweightconcrete(LWC). Anewmixdesigntoproducegrade25geopolymerOPSLWCwithinadensity rangeof1600-1900kg/m3isproposed;thiswillhavestrengthtodensityratio of16comparedto10oftheconventionalconcrete.Furthervarioustestson freshandhardenedconcretewillbecarriedout.Microscopicanalysisusing XRD, FESEM tests are planned to investigate the polymeric reaction and structureofthenewlydevelopedconcrete. Objectives Methodology Outcome Themainobjectiveofthisresearch istodesignanoptimummixdesign todevelopgeopolymerconcreteof compressive strength of 25 MPa usingtwolocalwastematerials.The secondobjectiveistounderstand the factors that influence the geopolymer concrete, including appropriate activators and their ratio. Further, the properties of OPS of acceptable particle size distribution, aggregate impact value,LosAngelesabrasionvalue, aggregate crushing values will be investigated. The microstructure of geopolymer OPS LWC using XRD and FSEM analyses will be investigated. The mechanical properties of OPS geopolymer concrete will be investigated and analyzed The following points give brief detailsonthemethodologythatis being adopted in this work. After thoroughliteraturereviewofoldand latest resources on geopolymer and OPS concrete, procurement of materials will be done. Procurementofmaterialsincludes fly ash, OPS, Alkali activators, etc. Since curing of geopolymer concrete is an important aspect, fabrication of curing chamberboiler for steam curing or heater fordrycuringwillbedone.Thisis significant due to polymerization of geopolymer concrete. Thus we need to have appropriate curing chamber (steam or dry curing). Testing of materials such as fly ash, OPS etc. will be carried out simultaneously followed by the mix design and trial mixes. After obtaining appropriate mixture design, preparation of mortar and concrete specimens for physical, mechanical and microscopic propertieswillbecarriedout.Tests for mechanical properties and microscopic analysis will be done next.Thelastphaseofthisventure includes data collection, analysis of tests results, preparation of articlesandreportwriting New geopolymer oil palm shell lightweight concrete (Geopolymer OPSLWC) HIR Annual report 2011.indb 40 Lowdensitymaterial New mix design for structural gradegeopolymerOPSLWC Microstructuralbehavior Possible High Impact Journals for Publications Constructing Materials and Building MaterialsandDesign EnergyandBuilding Cementandconcretecomposites EngineeringStructures Collaborators(Overseas) Prof. Dr. Chun-Qing Li, RMIT University,Australia Assoc.Prof.Dr.ManuSanthanam, Indian Institute of Technology Madras(IITM),India Dr. Andrew Tyas, University of Sheffield,UK Prof. Dr. Hamid Nikraz, Curtin University,Australia 24/05/2012 9:44:51 High Impact Research Annual Report 2011 41 Project No: UM.C/625/1/HIR/094 Title: Development of Fuzzy-AHP Holistic Risk Assessment Model Using Analytic Hierarchy Process (AHP) Based on Fuzzy Synthetic Analysis (FSA) Principal Investigator : Professor Dr. Hamzah Abdul Rahman Faculty : Department of Quantity Surveying, Faculty of Built Environment SummaryofResearchProposal Inmanycircumstances,thecurrentconstructionriskassessmenttoolscould not deliver satisfactory results due to insufficient consideration on project objectivessuchastime,cost,andquality.BasedonFuzzySyntheticAnalysis (FSA), a model development team will be formed among construction engineers, IT professionals, and Mathematicians in developing a holistic risk assessment model to estimate the construction risks especially for the situationswithincompletedataandvagueenvironments.Throughqualitative scalesdefinedbytriangularfuzzynumbersusedinpairwisecomparisonsto capture the vagueness in the linguistic variables, a risk assessment model using Analytic Hierarchy Process (AHP) will be developed. The developed Fuzzy-AHP HRAM is supposed to accelerate the decision-making process andprovideoptimalallocationofprojectresourcestomitigatepossiblerisks detrimentaltothesuccessofaprojectintermsoftime,cost,andquality.A trial run of this Fuzzy-AHP model will be conducted in real construction in thisstudy. HIR Annual report 2011.indb 41 Objectives Methodology Outcome BasedonFuzzySetTheory(FST), this study intends to develop a holistic risk assessment model usingtoestimatetheconstruction risks especially for situations with incomplete data and vague environments The authors will adopt the FuzzyAHP technique as the decisionmakingframeworkforconstruction risk analysis in the developed modelsincetheFuzzy-AHPallows a more accurate description of the subjective data, where the fuzzy pairwise comparisons are morerationalinreflectingexperts’ uncertain judgments than a crisp one.Suchamodelcouldfacilitate the decision-making process, where the complex uncertainty inherited in subjectivity is able to be captured and mitigated optimally Throughqualitativescalesdefined by triangular fuzzy numbers used inpairwisecomparisonstocapture the vagueness in the linguistic variables,ariskassessmentmodel using Analytic Hierarchy Process (AHP) will be developed. The proposed Fuzzy-AHP HRAM will beabletoacceleratethedecisionmaking process and provide optimal allocation of project resources to mitigate possible risks detrimental to the success ofaprojectintermsoftime,cost, andquality The proposed Fuzzy-AHP HRAM is to holistically solve multicriteria complex problems in the real practice of construction. The algorithm of the proposed model consistsofsixphases Possible High Impact Journals forPublications 1. Establishment of AssessmentTeam Information&Management 2. StructureaHierarchyTree Organizational Behavior HumanDecisionProcesses 3. Pairwise Comparison using FuzzyComparisonScale Journal Of Management 4. Aggregation of Individual TFNsintoGroupTFN Collaborators 5. CalculationofPriorityWeighs atDifferentHierarchyLevel 6. SynthesizationofResults Risk AutomationinConstruction BuildingResearchandinformation And Operations Nil 24/05/2012 9:44:51 42 High Impact Research Annual Report 2011 Project No: UM.C/625/1/HIR/095 Title: Exploring the Cardiovascular Mechanism for the Potential use of Quercetin as adjuvant to Metformin/ Pioglitazone in management of Type 2 Diabetic Rat Model Principal Investigator : Dr. Dharmani Devi a/p Murugan Faculty: Department of Pharmacology, Faculty of Medicine SummaryofResearchProposal Diabetesisaglobalhealthconcernthatrequiresseriouseffortbyallnations towards arresting its scourge. Study by Wild et al., (2004) indicated that the prevalence of diabetes amongst all age-groups worldwide is estimated to increase from 2.8% in 2000 to 4.4% in 2030. Diabetes is characterized by chronic hyperglycaemia, and over time, results in serious harm to many body systems, including the blood vasculatures. Hyperglycaemia leads to oxidative stress which is seen as increased production of reactive oxygen spesies (ROS) and ultimately leads to development of endothelial Recent treatmentofdiabetesismainlyfocusedonmaintainingnormalbloodglucose byusinginsulinororalhypoglycaemicagents.Recentmeta-analysisstudies haveshownthatalthoughsomeoftheoralhypoglycaemicagentsimproved serumlipidprofileandtriglyceridelevels,overalltheyhavenotmuchimpact in cardiovascular disease. Thus, bioactive molecules which are capable of exertingpotentfreeradicalscavengingandantioxidantactionmayresultin bettervascularprotectiveactionindiabetes. Natural polyphenolic compounds such as flavonoids, which are found predominantly in human diets such as fruits and vegetables, have been showntoexertpotentfreeradicalscavenging/antioxidantactionsinvitro. Previousworkinourlaboratoryhasshownthatquercetin,apotentantioxidant improvedendothelialdysfunctioninstreptozotocin-induceddiabeticmodel. Thusfar,therearenoreportsonchroniceffectofflavonoidsincombination with other anti-diabetic drugs on vascular function in diabetesin either animal or human models. The fact that the flavonoids possess antidiabetic propertiesandshowimprovementinvascularfunction,theuseofflavonoids in combination with anti-diabetic agents like metformin or pioglitazone, producetherapeuticinteraction.Theinteractionmaybeadditive,synergicor antagonistic.Therefore,itisnecessarytocarryoutasystematicinvestigation intotheeffectofsuchcombinations. Objectives Methodology Outcome To determine the effect of quercetin treatment on the antidiabetic profile of metformin / pioglitazone, commonly used oral hypoglycaemicagents NIDDMmodelwillbeinducedusing nicotidamideandstreptozotocinin Sprague-Dawley rats. The rats will be divided to several treatment groups: Group 1: Vehicle; Group 2: Quercetin (10mg/kg) (Ajay et al., 2006); Group 3: Quercetin + metformin(180mg/kg)/Pioglitazone (2.7mg/kg); Group 4: Metformin (180mg/kg) / Pioglitazone (2.7mg/ kg); Group 5: Untreated. 4 weeks afterthetreatment,theanimalswill besacrifiedandtheisolatedaortic andmesentericringswillbetested forvascularrelaxationandreactive oxygen spesies production. Blood collectedwillbeusedtoinvestigate Hb1Ac, plasma insulin, plasma lipid prolife and antioxidant assay. Kidney, liver and pancreas from the treated groups will undergo histologicalexamination To understand the interaction betweenquercetinandantidiabetic agents Todeterminetheeffectofquercetin and metformin / pioglitazone combinationonaorticandresistnce (Mesentericarteryandrenalartery) v ascular function of a type 2 diabetesratmodel To determine the effect of PVAT on the cardiovascular effect of quercetin and metformin / pioglitazonecombination HIR Annual report 2011.indb 42 Possible High Impact Journals forPublications BritishJournalofPharmacology PLoSOne PharmacologicalResearch JournalofClinicalPharmacology CirculationResearch Collaborators Prof. Dr. Mohd Rais Mustafa, UniversityofMalaya(UM) Prof. Dr. Francis I Achike , William CareyUniversity,Mississippi Prof.Dr.MakJoonWah,International MedicalUniversity(IMU) Mr. Jestin Chelliah, International MedicalUniversity 24/05/2012 9:44:51 High Impact Research Annual Report 2011 43 Project No: UM.C/625/1/HIR/096 Title: Circulating microRNAs as Novel Biomarkers for Early Detection of Atherosclerosis Principal Investigator : Professor Dr. Wan Azman Wan Ahmad Faculty : Department of Medicine, Faculty of Medicine SummaryofResearchProposal The importance of microRNA (miRNA) in diseases has been recognized overtheyearswithmountingevidenceoftheirexistenceandcontributionto diseases. miRNA expression profiles between normal and diseased tissues have identified signatures that enable disease classification, progression, diagnosis and prognosis. The presence of miRNAs, termed circulating miRNAsinbodyfluidsincludingserum,plasma,urine,salivaandbreastmilk haspromptedvariousinvestigationsintotheirusefordiagnosisandprognosis of various cancers and cardiovascular diseases. While these miRNAs may beusefulinthediagnosisoffullblowncardiovasculardiseases(CVD),there arenoreportsoncirculatingmiRNAthatcanbeamarkertopredictpatients who will develop accelerated or premature atherosclerotic diseases and also to identify circulating miRNAs that can be used to detect vulnerable atherosclerotic plaques which can predispose patient to acute coronary syndrome.Identficationofprematureatherosclerotic-associatedmiRNAswill be useful in early detection and treatment of atherosclerotic diseases and preventionofacutecoronarysyndromecomplications. Objectives Methodology The objective of this study is to identify circulating miRNAs for earlydetectionofatherosclerosis. miRNAs profiles of patients who presented with accelerated atheroclerotic disease will be evaluated. Three groups of study populationwillbeinvolved.Group one are patients with accelerated atherosclerotic disease and has signicant conventional cardiovascular risk factors. Group two are patients with accelerated atherosclerotic disease but has no significant conventional cardiovascular risk factors. Group threearehealthycontrol.InGroup oneandtwopopulations,patients can present as stable angina or as acute coronary syndrome. Diagnosis of established coronary artery disease is confirmed by coronaryangiogram.Thediagnosis of patient having vulnerable plaque will be based on clinical presentationandfurtherconfirmed by intravascular imaging during coronaryangiogram.Differentially expressed miRNAs that may be associated to premature atherosclerosis or vulnerable atherosclerotic plaques will be identified following bioinformatic analysis. qRT-PCR will then be performed on a different cohort of patients and compared with their angiography, plasma Thespecificaimsare HIR Annual report 2011.indb 43 1. To identify circulating miRNA thatcanbeamarkertopredict patients who will develop accelerated atherosclerotic diseases 2. To identify circulating miRNA that can be used to detect vulnerable atherosclerosis and its response to intervention 3. To investigate if there are ethnic variations in the miRNAspresentedinpatients comprising of three major ethnic groups i.e. Malay, ChineseandIndian 4. To determine if dysregulation ofatherosclerosis-associated miRNAaconsequenceof,or precedesatherosclerosisand myocardialinjury lipid, C-reactive protein and proinflammatorycytokinesprofiles to validate their usefulness and specificity in identifying patients withriskofdevelopingaccelerated or premature coronary artery disease and also to differentiate patientwithvulnerableplaqueand stableplaque Inaddition,patientswithvulnerable atherosclerosis plaques will be given antihypercholestrolaemia drugs such as statins and their serum miRNAs level will be monitored from time to time to clinically validate the usefulness of the identified miRNAs as atherosclerosis indicators. Apart from clinical validation, selected miRNAs will be investigated in vivo using ApoE knockout mice to determine their precise role and mechanisms involved in endothelial dysfunction and atherosclerosis. Results from the proposedstudywouldprovidenew insightsintotheroleofmiRNAsin atherosclerosis and their use in early detection and treatment of atheroscleroticdiseases 24/05/2012 9:44:51 44 High Impact Research Annual Report 2011 Outcome Identification of novel marker for early detection of atherosclerosis/ coronaryarterydisease Identificationofthemechanismof theregulationofatherosclerosisby miRNAs Correlation of circulating miRNAs to angiography and plasma lipid, C-reactive protein and other biomarkersofatherosclerosis Possible High Impact Journals forPublications Collaborators Angiogenesis,IF6.188 Prof. Mohd Rais Mustafa, Faculty ofMedicine,UniversityofMalaya British Journal of Pharmacology, IF4.925 Dr. Wong Pooi Fong, Faculty of Medicine,UniversityofMalaya EuropeanHeartJournal,IF10.046 Dr. Ahmad Syadi bin Mahmood Zuhdi, Faculty of Medicine, UniversityofMalaya CirculationResearch,IF9.504 CardiovascularResearch,IF6.051 The usefullness of monitoring serum miRNAs as treatment decisionforatherosclerosis Dr. Dharmani Devi Murugan, Faculty of Medicine, University of Malaya Prof. Paul M. VanHoutte, Li Ka Shing, Faculty of Medicine, Hong KongUniversity Project No: UM.C/625/1/HIR/053 Title: Sustainable Energy Production from Palm Oil Industry Wastewater Using Microbial Fuel Cell Principal Investigator : Dr.Saravanan Pichiah Faculty : Department of Civil Engineering, Faculty of Engineering SummaryofResearchProposal A Microbial Fuel cell (MFC) is a bioreactor which converts chemical energy in the organic compounds in to electrical energy by catalytic reactions of microorganisms under anaerobic conditions. The fuel for the MFC is Biomasswastesandthefeedstockdoesnotrequireanyextensivefeedstock conversionmethod. Therefore this technology can be applied as a new waste water treatment method,sincethisremovesorganicmatterfromwastewaterstreamswhile generatingelectricity.EventhoughMFCtechnologyisstillatitsearlystages of technology development and the power output from this type of cell is limitedtofewthousandmWs,thishasgreatpotentialtoaddresssomeofthe globalissueslikeglobalwarmingandenergycrisis. The objectives of this research are identifying waste biomass (palm oil industrywastewaterhasTOCof30,000mg/L)whicharefreelyavailableand their operational suitability to use as a feed stock for MFC. Analysing the currentpotentialofMFCandidentifyingspecificissuesfacingscalinguptoa usefuloperationallevelarealsosomeoftheobjectivesofthisresearch. Methodology Objectives The main focus is to develop sustainable technology for environmentremediationofenergy scarcity and treatment of effluent generatedfrompalmoilindustry Hydrogen and electricity production from palm industry effluent using MFC will be investigated in the lab- scale model HIR Annual report 2011.indb 44 Optimization of process and identification specific issues of scaleupwillbeinvestigated To evaluate the system performanceintermsofhydrogen recovery,currentefficiencyandthe effectiveness of effluent treatment process TheMFCreactorisplannedtobe constructed of acrylic material. Inthereactor,asampleportand twoinletsareconstructedandtwo partitionswillbeinstalledtoobtain abatchorflowmodepatternwith a total volume of 1000 ml. MFC ismadeupoftwocompartments, viz.,anodeandcathode,separated byaprotonexchangemembrane (NafionY 117). The CEM was pretreatedbyboilinginH2O2(30%) 24/05/2012 9:44:51 High Impact Research Annual Report 2011 Outcome and deionized water, followed by 0.5M H2SO4 and deionized (DI) water,eachfor1h,andthenstored in DI water prior to being used. Both the electrodes, anode and cathode, made of DSA have an area of 100 cm2 each. Electrodes aresoakedinDI waterfor1daybeforetests.Copper wire inserted inside fluorinated ethylene propylene tubing is used to connect the electrodes and all exposed metal surfaces are sealed with a nonconductive epoxy. During the experiment of after each batch cycle, the gas composition is analyzed by gas chromatography using a gas tight syringefromthereactor HIR Annual report 2011.indb 45 New concepts, processes and technologies in wastewater treatment with potential benefits for the stable quality of effluents finally discharged, energy and operational cost savings and protectionoftheenvironment 45 Possible High Impact Journals forPublications BioresourceTechnology JournalofBiotechnology WaterResearch ChemicalEngineeringJournal BiochemicalEngineeringJournal Collaborators Dr. M. Matheswaran, NITTiruchirappalli,India Dr.P.Gopinath,IITRoorkeeIndia 24/05/2012 9:44:51 46 High Impact Research Annual Report 2011 RESEARCH PROPOSAL (HIR-MoHE5Years) FacultyofMedicine Project No: UM.C/625/1/HIR/MOHE/MED/01 Title: Mitigating the HIV Epidemic through A Comprehensive Research Program Principal Investigator : Professor Dr. Adeeba Kamarulzaman Faculty: Centre of Excellence for Research in AIDS (CERiA) Health & Translational Research Cluster, Faculty of Medicine SummaryofResearchProposal HIVinfectionremainsaseriousprobleminMalaysiawithmorethan90,000 casesreportedtodatetotheMinistryofHealth.Ithasbeenestimatedthat by2015,200,000Malaysianswillbecomeinfectedifinterventionstoprevent transmission are not implemented. An unchecked HIV epidemic will have tremendous impact on the socio-economic and developmental progress ofthenation.SlowingdownandreversingtherateofHIVandtuberculosis infectionshasbeentheonlyMillenniumDevelopmentGoalthatthecountry hasfailedtoachieve. Our research program builds on existing research activities conducted by CERiA to better understand the HIV epidemic in Malaysia focusing on the currently most affected community ie drug users including the molecular epidemiology of HIV transmission in the country. The research also looks attheepidemiologyandclinicalimpactofcoinfectionofHIVwithotherkey infectionsnamelytuberculosis,hepatitisCandHPV.Intheareaoftreatment, research will be conducted to better understand the immunogenetics and immunopathogenesisofimmunereconstitutionfollowingantiretroviraltherapy Objectives Our program aims to study major healthandsocialissuesassociated withtheHIVepidemicinMalaysia focusing on prevention and treatment in communities most at risk and vulnerable. Our clinical and basic science research aims to understand treatment-related issues including (i) the impact of co-infections(HCV,TB,HPV,CMV) on clinical outcomes and explore theimmuno-pathogenicpathways involved, (ii) to understand the molecularandevolutionarybiology of viruses (HIV, HCV) to monitor drugresistancepatternsandinform vaccine development strategies and(iii)toexploretheinfluenceof host genetics on overall immune recovery. Our epidemiology and social science program focuses on designing and testing targeted HIR Annual report 2011.indb 46 Methodology prevention interventions by (i) establishing how HIV prevalence in most at risk (drug users, men who have sex with men) and in vulnerable sections of the population (prisoners, fishermen) are linked to (ii) underlying social and structural factors that contributetohigh-riskbehaviours, and (iii) the disease burden on local communities. The centre is uniquelypositionedtodothisasit has (i) a broad range of expertise with strong international links and (ii) established collaborations with key players including government agencies and NGOs, increasing our opportunity to strongly influence evidence-based policies andpractice The research program consists of 5 research projects several of whicharebuiltonexistingresearch activitiesandareinter-related: 1. ImpactofEarlyAnti-Retroviral Therapy Introduction on TB incidence among HIV infectedinmatesinMalaysia: ALongitudinalCohortStudy 2. AProspectiveStudyCorrelating Human Papillomavirus (HPV) Carriage and Its Associated Pathology and Host Immune FactorsinMalaysianCohortof HIV+Patients 3. Identifying Novel Host Determinants of Immune Recovery Following Combination Antiretroviral Therapy (cART) among HIVInfectedPatientsinMalaysia 24/05/2012 9:44:51 High Impact Research Annual Report 2011 4. 5. PathogenesisofTuberculosis Associated Immune Reconstitution Inflammation Syndrome(TB-IRIS) Assessment of HIV/HCV Prevalence and Risk Behaviour towards a PeerLed Prevention Intervention Among Fisherman in PeninsularMalaysia Outcome Collaborators Better understanding of the epidemiology and the social drivers of the HIV epidemic in Malaysia YaleUniversity BetterclinicalmanagementofHIV and its associated coinfections includingTBandHPV ColumbiaUniversity National Institute of Infectious Diseases,Japan MonashUniversity UniversityofWesternAustralia Better understanding of the mechanisms associated with immunereconstitution SydneyUniversity Possible High Impact Journals forPublications LeidenUniversity,Netherlands ClinicalInfectiousDiseases JournalofInfectiousDiseases PLoSMedicine 47 Burnet Australia Institute, Melbourne JabatanPenjaraMalaysia LembagaKemajuanIkanNegara KementerianKesihatanMalaysia UniversitiSainsMalaysia AmericanJournalofPublicHealth Project No: UM.C/625/1/HIR/MOHE/MED/02 Title: Genomics and Molecular Characterization of Tropical Infectious Disease Agents Principal Investigator : Professor Dr. Sazaly Abu Bakar Faculty : Department of Medical Microbiology, Faculty of Medicine SummaryofResearchProposal: Sub-Project 1: Acinetobacter baumannii has emerged as a pathogen of significantclinicalimportance,especiallyinhospitalsettingswhenonlyfew antibioticswerereportedtobeeffectiveforthetreatment.Ourstudyisaimed atunderstandingthetheimmuneresponsesagainstthisbacteria. Sub-Project2:Potentialforprolongedlatencyandrecrudescenceisamong the major problems faced with B. pseudomallei infections. In many cases, relapse resulting from reactivation of a persistent endogenous source of infection have been reported. This suggests that intracellular survival of B. pseudomalleiplaysanimportantroleinpathogenesisofinfection. Sub-Project 3: Respiratory tract infections caused by viruses such as respiratory syncytial virus, parainfluenza, and influenza viruses are major causes of morbidity and mortality in children. A comprehensive picture of clinical and molecular epidemiology in Malaysia may provide insights into virus evolution and pathogenesis, and therapeutic interventions such as vaccines. Sub-Project4:Rickettsialdiseasesincludingscrubtyphus,murinetyphusand spottedfeverarefrequentlyassociatedwithundiagnosedfebrileillnessesin thedevelopingcountries.Itisimportanttounderstandtheinfectiousdisease threats,improvediagnosticmethods,characterizethecausativeagentsand determinetheinteractionsbetweenvectorsandreservoirhosts. Sub-Project5:Itispresentlynotknownwhethertheenterovirus71(EV-71)and coxackievirusA16(CV-|A16)viruseshavebeencirculatingforawhilebefore causinglargeoutbreaks.Inthepresentstudy,weproposedtoexaminethe phylodynamicsofEv-71andCV-A16. Sub-Project 6: Factors contributing to pathogenesis in Nipah virus (NiV) infection include the circumvention of the host immune response by NiV proteins and the ability of NiV to infect several cell types. This study is HIR Annual report 2011.indb 47 24/05/2012 9:44:51 48 High Impact Research Annual Report 2011 importanttobetterunderstandthepathoimmunologyofNiVfortheprevention andcontrolofthedisease. Sub-Project 7: Chlamydia trachomatis is the cause of bacterial sexually transmittedinfectionthatcause92millionnewcasesannually.Thoughhost immuneresponsecaneffectivelyeradicatethisinfection,factorsassociated withadaptiveimmuneresponsehavenotfullyelucidated.Therefore,weneed todeterminelocalmarkersforwomeninpredictingthisinfection. Sub-Project8:Therearemanyconventionaldiagnosticmethodsforparasitic infections such as microscopy method, molecular methods and serology methods. However, the difficulty of blood stage cultivation of parasite has beenhinderingtheuseofthesemethodologies.Inthisstudy,weproposed to develop more rapid and effective diagnostic methods for diagnostic for medicallyimportantparasiticinfection. Sub-Project 9: This is a 3-year study to determine bacterial genomic differencesthatmightshedsomelightontheapparentneurotropismofsome strainsofMycobacterium tuberculosis (MTB) Sub-Project 10: Hyaline hyphomycetes are the most common saprophytic fungi found in soil and decaying vegetation in the hot humid tropical countries.Thesefungiareimportantopportunicpathogensassociatedwith highmorbidityandmortalityinimmunosuppressedpatients.Identification of based on microscopic morphology is difficult and DNA sequencing are used to identify isolates but many remain unassigned. Sub-Project11:Currently,thereareseveralinfluenzavirusvaccinesavailable, howevertherearepotentialrisksassociatedwithmostofthesevaccines.In thisstudy,aprobioticbacteriumtodeliveranoralinfluenzavirusvaccineis investigatedanditsprotectivepotentialasacandidatevaccineisexamined. Objectives: Methodology: To develop knowledge and tools for the prevention and control of infectiousdiseasesindiagnostics, surveillance, treatment and prevention Sub-Project 1: Acinetobacter baumannii isolated from patients admitted to University Malaya Medical Center will be used to infect mice and the immune responses towards the bacteria willbeexamined Sub-Project 2: Adherence, invasion and survival of B. pseudomallei will be determined anditsintracellularlocationduring infection will be identified using different microscopy analysis techniques. Proteomics and microarray analysis of host genes willbeusedtoidentifytheproteins that might contribute to the entry and intracellular survival of the organism Sub-Project3:Respiratoryviruses collected in University Malaya Medical Centre over the last 15 years will be sequenced and analysed using bioinformatics methods to better understand evolutionary dynamics. Clinical datawillbecollectedtodetermine epidemiology and burden of respiratory viral disease in Malaysian children, including the contribution of emerging respiratoryviruses HIR Annual report 2011.indb 48 Sub-Project 4: Clinical data of patients suspected with rickettsioses will be collected. Field work will be conducted to trapanimalreservoirsandpotential vectors.Molecularapproacheswill beusedfordetectionofrickettsiae from various types of samples and to determine the genetic relationships between various speciesofrickettsiae Sub-Project 5: The viral genetic signatures of EV-71 and Cv-A16 willbedetermined.Seroprevalence of EV-71 and CV-A16 in the population will be determined. Immunogenic epitopes of EV-71 and CV-A16 will be identified and crossprotectionbetweendifferent EV-71 and CV-A16 subgenotypes willbeexamined Sub-Project6:SelectedNiVgenes willbeclonedandtransfectedinto eukaryotic cells for examination and comparison of cellular immuneresponse.Besidesthat,a blood brain barrier model for NiV infection will be established and investigated Sub-Project 7: The Malaysian femaleatreproductiveagepositive willberecruited.Thesamplewhich 24/05/2012 9:44:51 High Impact Research Annual Report 2011 willbeusedareblood,endocervical swabs and cervical washes. Antibody assay, quantification of serumcytokines,HLAtyping,flow cytometryandRNAextractionwill also be adopted in this study to reachtheobjective Sub-Project 8: LAMP, realtime PCR and ICT tests will be developedbasedonnewtargeted genes. Samples will be collected andtestedusingtheoldandnew methodstocomparethesensitivity andspecificity Sub-Project 9: Clinical isolates of MTB from respiratory secretions and CSF will be subjected to suppression subtractivehybridizationandPCR amplification to obtain subtracted sequences. These sequences will be cloned and selected for the making of probes used to identify CSF-specificsequencesinalarger collectionofclinicalisolates Sub-Project10:Allfungalisolates identifiedtogenuslevelbasedon morphology approach, grown on Saboraud Dextrose Agar (SDA) andincubatedat30°Cfor5days. Fungal suspension in PBS was usedforDNAextraction,PCR and sequencing.DNAsequenceswere analyzed and phylogenetic trees were constructed by neighborjoining(NJ)methodandmaximum likelihood(ML)method Sub-Project 11: Purified influenza antigenic proteins will be displayed on probiotic bacterium and administered into mice. The mice will be challenged, and the humoralimmuneresponseagainst the virus, cell-mediated immune response and viral clearance will beexamined Outcome: Sub-Project 1: Host immune responsesagainstA.baumannii Sub-Project 2: Understand molecules that aid entry and survivalofB. pseudomallei Sub-Project 3: Understanding the epidemiology and evolution of respiratoryvirusesinMalaysia. Possible High Impact Journals forPublications: International Journal AntimicrobialAgent of PLOSPathogen InfectionandImmunity PLoSOne JournalofClinicalMicrobiology Sub-Project4:Betterunderstanding ofrickettsiosesandidentificationof rickettsialpathogens American Journal of Tropical MedicineandHygiene Sub-Project 5: Identification EV71 and CV-A16 antigenic protein mutation hot spots important for vaccinedesign FEMS Immunology & Medical Microbiology Sub-Project6:Betterunderstanding of infection establishment and cellular immune responses upon NiVinfection JournalofImmunology Sub-Project7:Provideinsightsinto the effect of a genital chlamydial infectiononlocalpopulations. MolecularPhylogenticEvolution Sub-Project 8: Specific and rapid detectionofparasiticinfections Collaborators: Sub-Project 9: Form the basis of genomicandanimalmodelstudies to determine the association of CSF-specific sequences with neurotropicviulence Prof.SheilaNathan,Prof.Rahmah Mohamed (Universiti Kebangsaan Malaysia) Sub-Project 10: To establish a systematiclaboratoryidentification of hyaline hyphomycetes based on morphology and molecular phylogeneticapproachusing ITS15.8S-ITS2sequences Sub-Project 11: Better understanding of candidate influenzavirusvaccineinproviding protectiveimmunity 49 JournalofGeneralVirology ImmunologyandCellBiology Mycology FungalGeneticsandBiology GenomeResearch Prof.NorazmiMohdNor(Universiti SainsMalaysia) Prof. Mohd Zaki Salleh (Universiti TeknologiMARA) Prof.RahaAbdulRahim,DrChong PeiPei(UniversitiPutraMalaysia) Prof. Bernard Arulanandam (UniversityofTexas,USA) Prof. Tom Solomon, Dr. Adjanie Patabendige (University of Liverpool,UK) Dr. Laurent Renia, Dr. Bruce Russell (Singapore Immunology Network,A*Star) MinistryofHealth,Malaysia University Malaya Medical Center, Malaysia J.CraigVenterInstitute,USA National Institute of Allergy and InfectiousDiseases,USA HIR Annual report 2011.indb 49 24/05/2012 9:44:51 50 High Impact Research Annual Report 2011 Project No: UM.C/625/1/HIR/MOHE/MED/03 Title: Molecular Mechanism of Drugs Action Principal Investigator : Professor Dr. Mohd Rais Mustafa Faculty: Department of Pharmacology, Faculty of Medicine SummaryofResearchProposal Cell signaling is defined as communications between and within cells that govern basic cellular activities and coordinate cell actions. Deregulation of cellular information processing can give rise to cancer, autoimmune diseases, diabetes and others. Hence, understanding normal cell signaling andcorrectionsofderegulatedsignalingnetworksindiseasestatescanbe potentiallyeffectivetreatmentstrategies. Naturalproductsremainanimportantsourcefordrugdiscoveryinviewofthe increasingneedsfordrugsthatcanovercomeissuesoftoxicityandresistance in cancer or infectious diseases. Bioactive compounds derived from local plantsandmarineorganismscanbeharnessedforthedevelopmentofnewer andbettertherapeutics.Toreducetoxicityandincreasetargetspecificity,itis importanttoidentifydrugsthatcanspecificallytargetandcorrectderegulated signaling pathways in the diseased cells. Correction of NF-κB pathway deregulationinmanyinflammatorydisordersandcancers,forexample,can help control aberrant expression of cytokines, apoptosis resistance and angiogenicgenes. Objectives Methodology This project is divided into 4 subprojectstomaptherespective mechanism of drugs action and identify drug targets along signaling pathways which are involved in inflammation, cancer development, angiogenesis and senescence High throughput methods such as high content screening (HCS) by Cellomics Arrayscan and real time cell analyzer (RTCA) will be used to screen and identify potential anti-inflammatory, anticancer, anti-angiogenic and premature senescence protective compounds. Data will be further validatedusingpathwayinhibitors and stimulators, immunoblotting, ELISA, PCR array analyses and in vivo study using nude mice xenograft Outcome Possible High Impact Journals forPublications PLoSOne,IF4.351 British Journal of Nutrition, IF 3.446 Biochemical Pharmacology, IF 4.254 Cellular And Molecular Life Sciences, IF 5.928 BritishJournalofCancer,IF4.346 InternationalJournalofCancer.IF 4.722 Evidence-based Complementary andAlternativeMedicine,IF2.064 Establishment of bioassays, in vivo assays and drug discovery infrastructureinUM Collaborators Identification of novel bioactive compoundswithanti-cancer,antiinflammatory, anti-angiogenic and premature senescence protective activities Associate Professor John David Hooper Newknowledgeonthemechanism of actions of novel bioactive compounds ProfessorGuyHaegeman DrWongPooiFong Assoc. Prof. Abdelwahab Siddig Ibrahim DrCheahShiauChuen DrSyamMohan Patents HIR Annual report 2011.indb 50 24/05/2012 9:44:52 High Impact Research Annual Report 2011 51 Project No: UM.C/625/1/HIR/MOHE/MED/04 Title: Improving Articular Disease Prediction and Management, Regenerative Therapy and SarcomaManagement Principal Investigator : Professor Dr. Tunku Kamarul Zaman Faculty : Department of Orthopaedic Surgery, Faculty of Medicine Summary of Research Proposal Musculoskeletal disorders have become one of the major health concerns all over the world owing to an increase in aging population and increased occurrence of sports-related injuries,. Current treatments, although fairly successful, do not provide the optimal outcome that is expected. These treatmentstypicallyrelyondonortissuesobtainedeitherfromthepatientor fromanothersource.Theformerraisestheissueofsupply,whereasthelatter posestheriskofrejectionanddiseasetransfer.Thishaspromptedorthopedic surgeons and scientists to look for viable alternatives. Tissue engineering / regenerativemedicineisanemergingmultidisciplinaryfieldinvolvingbiology, medicine,andengineeringthatislikelytorevolutionizethewaysweimprove the health and quality of life for millions of people worldwide by restoring, maintaining,orenhancingtissueandorganfunction. Objectives Methodology UsingMesenchymalstemcells: Project 1: Optimization of different inductions methods of Osteoarthritis in Rat and rabbit followed by isolation and characterization of Mesenchymal Stem Cells (MSC) from rat bone marrow is first performed. Administration of Mesenchymal stem cells and Hyarulonic acid is used as a therapeutic options. Thentheanimalswillbesacrificed for further histopathological Assesment, biochemical analysis by Glycosaminoglycan (GAG) and Total protein (TP) and microindentionAssesment Project 1: We hope to investigate and develop an effective therapy forosteoarthritisinthethreemost commonly used animal models (rat, rabbit and goat) thereby translating the finding for huma application Project 2: In addition, we aim to verify the effect of microfracture on the healing of the articular cartilagedefectandtoinvestigate the effect of hyaluronic acid (HA) and combination of intra-articular HA and intra-articular autologous BMMSCsonthehealingofarticular cartilagedefectingoatswhichhad undergonemicrofractures Project 3: Another study embarks on to investigate the affinity of osteosarcoma metastasisassociated secreted proteins. This is followed by assessing the effectofsecretedproteinactivated integrin signalling on β-catenin regulation and on cytoskeleton arrangement. Furthermore this study also evaluates whether ostegenic lineage differentiated mesenchymal stem cell can be used as a regenarative medicine forosteosarcoma Project 4: This study aims to characterize and understand the effects and evaluation of naturally occurring growth factor on cell proliferationandpathwayinduced differentiation HIR Annual report 2011.indb 51 Project 2: Isolation and characterization of cultured MSC from Boer goat. Chondral defects are created in goat knees. After 6 weeks, they were either treated with microfracture, HA, BMMSC’s or combination of HA and MSC’s. After 24 weeks, goats are sacrificed for further histological, biochemical and gene expression analysis Project3:TissueBiopsy-Primary culture of osteosarcoma cells will be established based on previous method (Yasuda et al., 2009). Extraction and purification of secreted proteins will be carried out using i-TRAQ labeling system and purification of secreted proteins will be carried out using i-TRAQ labeling system. Target proteins will be analysed for its affinity towards integrin protein of the lung cells using protein microarray technique. β-catenin regulation by the secreted proteinswillbeassessedbygene transfectionfollowedbyLuciferase assay. Cell behaviour will be carried out using wound healing assay, migration assay, invasion assay and intracellular calcium ion level upon knock-down of the metastasis-specific secreted protein genes. Cytoskeleton arrangement observation will be carried out by immunoflourescent analysis upon knock-down of the secreted protein genes. Osteosarcoma will be created in a knock-out/immunosupressed mice and ostegenic lineage differentiated mesenchymal stem cells will be injected with GFP andfurtheranalysiswillbecarried out. All statistical analysis of data collected will be carried out by statisticalsoftware,SPSSver.17 Project4: Part 1: Preparation of thrombinactivatedPRPandinactivatedPRP and optimization, isolation and cultureofhumanMSCs.Followed by in vitro effect of thrombin activated PRP and thrombin inactivated PRP on cell growth/ proliferation and on Akt/PKB, and ERK1/2pathwayactivation. Part 2: Isolation and culture of human MSCs and cells seeding. Application of mechanical stretch on the seeded cells to check cell proliferation rate followed by immunoblottingandotherassays, 24/05/2012 9:44:52 52 High Impact Research Annual Report 2011 cell signaling, western blot or ELISAtechniques for global MMP activity Outcome Use of MSC therapy in osteoarthritis rat knees offers a betterunderstandingofthedisease andactsasapromisingtreatment forfutureclinicalapplications The results from this study may provide us with knowledge to improve our understanding in cartilage repair methods and provide better application procedures in tissue engineering techniques involving the repair of cartilagedefects Increase understanding of the molecular event in OS metastatic cascade provides the possiblity of using ostegenic lineage differentiated mesenchymal stem cellasatherapy Determiningthepathwayregulation of thrombin activated and inactivated Platelet rich plasma in cell activity. We will be able to find support for a critical role of PRP in activation of MSCs and also can provide further evidence on mechanotransduction pathway involvedinactivetissuerepair Collaborators Possible High Impact Journals forPublications Dr. Chim C Lang, Centre for Cardiovascular & Lung Biology, Division of Medical Sciences, College of Medicine, Dentistry & Nursing, Ninewells Hospital & MedicalSchool OsteoarthritisandCartilage JournalofBoneandJointSurgeryAmericanVolume Prof. Dan Badder, School of Engineering and Material Science QueenMary,UniversityofLondon (QMUL),UnitedKingdom Assoc.Prof.JamesWang,Director oftheMechanoBiologyLaboratory, Department of Orthopaedic Surgery,UniversityofPittsburgh JournalofOrthopedicResearch JournalofBoneandJointSurgeryBritishVolume American Medicine Journal of Sports Project No: UM.C/625/1/HIR/MOHE/MED/05 Title: Pharmacogenomics Studies Principal Investigator : Professor Datin Dr. Zahurin Mohamed Faculty : Department of Pharmacology, Faculty of Medicine SummaryofResearchProposal Human genetic variation contributes substantially to variation among individuals including their susceptibility to diseases and their response to drugtreatment.Pharmacogenomicsisastudyofhowvariationinthegenetic make-up of individuals affect their disease susceptibility and the way that theseindividualsrespondtodrugtreatment.Threeprojectshavebeenplaced underthisumbrellaprojectonPharmacogenomicsStudies: Project 1 - Nonalcoholic fatty liver disease (NAFLD) (PI- Prof Rosmawati Mohamed): Introduction: NAFLD, which is one of the most common causes of chronic liverdiseaseworldwide,isassociatedwithanincreasedriskofcardiovascular eventsandliverrelatedmortality.CurrentmethodsofdiagnosisofNALFDare unabletodifferentiatethebenignformoffattyliver,simplesteatosis,fromthe progressiveform,non-alcoholicsteatohepatitis(NASH),exceptbyperforming aninvasivetest,whichisliverbiopsy.PatientswithNASHareathighriskof progressiontocirrhosisandlivercancer. Objective:Theaimforthisprojectistodevelopacustommicroarrayprototype forearly,cost-effectiveandaccurateprognosticsanddiagnosticsofNAFLD basedonAsiangeneticprofiles.Methods:Themethodologyinvolvesanovel microarraythatisabletodetectsinglebasechanges(SNPs)aswellassmall andlargegenomicdeletionsandamplificationsandIndelsonthesamechip. Project 2 – Epilepsy (Prof Zahurin Mohamed): Introduction: Idiopathic epilepsy is the most common group of inherited seizures contributed by multiple genes and environmental factors. Many genes and their variants such as copy number variations (CNVs) involve in HIR Annual report 2011.indb 52 24/05/2012 9:44:52 High Impact Research Annual Report 2011 53 epilepsysusceptibility.RareCNVsdeleteorduplicatetypicallylargergenomic segments thereby are more likely to be associated with disease. They are recurrentandmaycontainmanydeletedorduplicatedgenes.Two Caucasian genome-wide association studies (GWAS) supported the function of rare CNVs in idiopathic epilepsy. They reported rare CNVs in 8.9% of affected individualsandplayimportantrolesinthegeneticetiologyofepilepsy.With this accumulation of data from Caucasian patients and given that genetic variantsarepopulation-specific,thereiscurrentlyaverylittleinformationon AsiansandparticularlyMalaysians.Here,weproposereplicatingtheprevious GWASinthetri-ethnicMalaysianswithahigherresolutionscreeningapproach thanthelastreports. Objective:Theaimofthisstudyistodeterminewhethergenomicvariantsare riskfactorsforsusceptibilitytoidiopathicepilepsyinthetri-ethnicMalaysian patients. Methods:Genotypingof1,000,000SNPsfordetectingrareCNVsin750case and control (750) recruited from 3 centers in UMMC, UKMMC, and GHKL hospitalwillbeperformed.KeyScopeandComponentsforthisProjectare as follows: (a) Population study: genotype-phenotype association study of 750 Malaysian patients affected by idiopathic epilepsy compared with 750 adjusted healthy controls. (b) Family study of recurrent CNVs: genotypephenotype association study of Malaysian patients affected by idiopathic epilepsywithrarecopynumbervariants Project 3 - Major Depressive Disorder (MDD) (Prof Nor Zuraida Zainal). Introduction: MDD is a condition that involves mood disorder and various abnormalitiesincognitionandphysicalactivities.Itisacommonpsychiatric disorderwhichisassociatedwithincreasedmorbidityandmortality.Patients withMDDarealsoknowntohavesleepandappetitedisorder. Sexual dysfunction is common among patients with MDD. Treatment with antidepressants such as Serotonin Selective Reuptake Inhibitors (SSRI) can also trigger sexual dysfunction in depressed people. In fact, sexual dysfunctionmaybethemostsignificantSSRI-relatedadverseeventamong depressedpeopleaged18-40. Objectives: The main goal of this study is to determine whether genomic variants are risk factors for susceptibility to MDD in tri-ethnic Malaysian patients. The effect of variations in the genes on sexual function during treatmentwiththeSSRIsinMDDpatientswillalsobestudied. Methods:ThevariantswillbegenotypedonaSequenomplatform. Possible High Impact Journals forPublications Pharmacogenomics HumanGenetics PLoSOne ResearchersandCollaborators: ProfSanjivMahadeva(UM) DrBatoulSadatHaerian(UM) ProfCTTan(UM) DrLimKheangSeang(UM) Assoc Prof Heather C Mefford (UnivofWashington) Assoc Prof Larry Baum (Chinese UniversityofHongKong) ProfNorZuraidaZainal(UM) Assoc Prof Kwan (Chinese UniversityofHongKong) AssocProfAhmadHatimSulaiman (UM) Prof El-Wui Loh (National Health ResearchInstitute,Taiwan) Prof Dato’ Raymond Azman Ali (UKM) ProfHJTan(UKM) ProfSWWong(UKM) DatoDrHanif(HKL) DrSoobithaSubenthiran(HKL) Assoc Prof John Dhillon (Univ of Dundee) Prof Lang Chim Choy (Univ of Dundee) HIR Annual report 2011.indb 53 24/05/2012 9:44:52 54 High Impact Research Annual Report 2011 Project No: UM.C/625/1/HIR/MOHE/MED/06 Title: Infectious Disease Pathology of Medically Important Pathogens with an Emphasis on Investigations by Molecular Approaches Principal Investigator : Professor Dr. Wong Kum Thong Faculty : Department of Pathology, Faculty of Medicine SummaryofResearchProposal Thefocusofthisprojectistostudythehumanpathologyofinfectiousdiseases including,firstandforemostviraldiseases,butalsoothermedicallyimportant pathogens. Investigation of the pathological and infective process using humantissuesiscriticaltoprovidevaluableinsightsintohumaninfections.In general,howeverthereisstillrelativelylittlepublished.Thisstudyisdrivenby thedevelopmentofnewermoleculartechniquessuchasspecificnucleotide probes, real time RT-PCR, next generation sequencing etc., for microbial identificationandlocalisationinrelationtoareasoftissuedamage. Inthelastdecadewehavedevelopedmanyproprietaryreagentsofourown thatwillenableustofurtherelucidatemicrobialpathogenesis.Inaddition,we shallmakeextensiveuseofourowngoodarchiveofhumaninfectiousdisease tissuesandthoseofourcollaboratorscollectedovertheyearstoachieveour goals.Forviraldiseases,thestudywillconcentrateonthreegroupsofvirus including flaviviruses, henipaviruses and enteroviruses in naturally infected humantissuesandalsoanimalmodels.Ifnewlydiscoveredvirusesarefound, itwillalsobeourprioritytoinvestigatethediseasescaused.Othernonviral diseases studied will be infections caused by medically important bacteria, fungusandPlasmodiaspeciesconcentratingonspeciesthatcausemortality. Objectives Methodology To investigate cellular targets and infectious disease pathology of flaviviruses, henipaviruses, enteroviruses, and other novel viruses (if available) in naturallyinfectedhumanandanimalmodel tissuesandorgans. Microscopy(lightandelectron) Develop novel molecular probe technology to study pathology of other medically important human pathogens (bacteria, fungus and Plasmodia species) in infected human and animal tissues, includingperipheralblood Naturallyhumanorexperimentally infected tissues will be formalin fixedandroutinelyprocessedand embedded as paraffin blocks. TissuesectionsarestainedbyH&E and examined for inflammation or other pathological changes. Appropriate 1x1 mm sections are fixed in 4% glutaldehyde or other suitablefixatives,resinembedded and the ultrathin sections examined. Immunogold and other EMmoleculartechniquesarealso suitabletostudythesetissues Immunohistochemistry Standard tissue sections are first reacted with the appropriate primary antibody before linked to other linking reagents to localise specific proteins of viruses, bacteriaandothermicrobes.After counterstaininginDAB,theslides areviewedtovisualisethemicrobe probe sequence (about 100-500 bp)sothatitcouldhybridisetothe target nucleotide sequence. The probeitselfispreparedbydoinga specific PCR or RT-PCR reaction togetanampliconthatcanlabeled bydigoxigeninbyincorporating11dUTPinasecondPCR.Duringthe ISH the probe is hybridized with thetargetsequenceofthemicrobe anditspresenceisdetectedbyan immunohistochemicalreactionthat utilises a primary antibody to the digoxigenin PCR/RT-PCR From the genbank and other published sequences appropriate primers for PCR and RT-PCR are generated. Conditions for the reaction is standard but could be optimisedforspecificmicrobes Insituhybridization(ISH) Thepreparationofthespecificprobe to target the microbial nucleotide sequence (DNA, or ribosomal RNA),involvesidentifyingaspecific HIR Annual report 2011.indb 54 24/05/2012 9:44:52 High Impact Research Annual Report 2011 Outcome We expect to find new cellular targetsanddiscovernewinfective disease pathological process of viral and other infections in infected human tissues that are previously unknown. This knowledge will help understand pathogenesis better and may lead to more targeted therapy or managementstrategies.Theprobe technology that is developed for various pathogens will be utilised for pathogenesis studies and also confirmatory diagnosis on clinical samples and microbial cultures that are suspected to be infected bythesepathogens Possible High Impact Journals forPublications Prof Catriona McLean, Prince AlfredHospital,Australia Journalofinfectiousdiseases Prof Benhur Lee, David Geffen SchoolofMedicine,USA Emerginginfectiousdiseases Clinicalinfectiousdiseases Actaneuropathologica JournalofVirology Collaborators DrBrankaHorvat,INSERM,France DrAnnaSalvetti,INSERM,France Dr Robin Buckland, INSERM, France Dr Christopher Broder, Uniformed ServicesUniversity,USA 55 Dr Kyaw Linn, Yangon Children’s Hospital,Myanmar Dr Khin Saw Aye, Immunology ResearchDivision,Myanmar Dr S.A.M. Kularatne, University of Peradeniya,SriLanka DrLuMin,PekingUniversityHealth ScienceCentre,Beijing,China ProfBishanRadotra,Postgraduate Medical Institute for Medical EducationandResearch,India Prof Shankar, Neuropathology, Bangalore,India Dept of NIMHANS, Project No: UM.C/625/1/HIR/MOHE/MED/07 Title: Analysis of Endocrine Disrupting Chemicals in Food and Environment (SUCXeS) Principal Investigator : Professor Dr. Mustafa Ali Mohd Faculty : Department of Pharmacology, Faculty of Medicine SummaryofResearchProposal Evidence suggests that environmental exposure to some anthropogenic chemicals may result in disruption of endocrine systems in human and wildlifepopulations.Someofthewellknownexamplesarethefeminization offishbynonylphenolorestradiol,andmuscalinizationofsnailbyorgano-tin compounds.Endocrinedisruptersareexogenoushormone-likecompounds which mimic natural hormones by occupying the binding site of hormone receptor. The other type of disruption mechanism includes antagonism of hormonesorinhibitionofthesynthesisandmetabolismofhormones.Many ofknownendocrinedisruptersareenvironmentalestrogensanditisforthis reason that feminization is often observed in the environment. In addition to estrogen-like compounds, some other endocrine disrupter is known to showanti-estrogenicactivity,orthyroidhormoneactivity. Disruptionofthe endocrinesystemwillleadtothefailureofreproductionandsubsequentlyto thelossofbiologicalspecies. Our research program on endocrine disruptors started several years ago by the formation of the University of Malaya Endocrine Disrupters research group. The aim is to explore the possible adverse effects suspected due to environmental chemicals on the reproductive and other high-integrated biologicalsystemsinhumansandanimals. Nationwide monitoring has been done in 2000 and 2001 in Malaysia to establish a baseline and a comprehensive database in Malaysia. The monitoringresearchinclude: • LeachingofbisphenolAfrombabyfeedingbottles • ToxicityofbisphenolAontestisandkidneys • ContaminationofEDCinriverwater • Phytoestrogensinlocalplants • PhytoestrogenscontentofcordbloodofMalaysians HIR Annual report 2011.indb 55 24/05/2012 9:44:52 56 High Impact Research Annual Report 2011 • Metabolismofphytoestrogens • Effectsofphytoestrogensonselectedtissues • Effectsofpesticidesonselectedtissues • DetectionofbisphenolAandphhalatesinfoodandfoodcontainers • Monitoringofpesticidesinriverwater,vegetablesandchildrenblood Project No: UM.C/625/1/HIR/MOHE/MED/08 Title: Neurology Research Group Principal Investigator : Professor Dr. Tan Chong Tin Faculty : Department of Medicine, Faculty of Medicine SummaryofResearchProposal TheNeurologyResearchGroupisamultidisciplinaryresearchgroupintegrating clinicalneurologywithgenetics,diseasemechanismandneurotherapeutics towards understanding neurological disorders. Some projects are involved in the clinical aspects of various neurological disorders while others take a geneticsandcellularapproachtowardsunderstandingdiseasepathology. Objectives Methodology Outcome Sub-Project 1: To determine the role of cytoplasmic dynein in regulating axonal pathfinding and synapseformation Sub-Project 1: A combination of proteomics,cellcultureandanimal models Sub-Project 1: Potential therapy forneurodegenerativedisorders Sub-Project 2: To investigate the possible association between cytoplasmic dynein and inherited neuropathies Sub-Project 3: To elucidate the c l i n i c a l - p a t h o l o g i c a l - g e n e t i c patternofmusculardystrophiesin Malaysia Sub-Project 4: To investigate the mechanism of EphA2 signalling andassociatedregulatorygenesin adhesion and fusion of the neural tube Sub-Project 2: Genetic analysis including mutation screening, linkage analysis and exome sequencing Sub-Project 3: A combination of clinical diagnosis, pathology tests andgeneticstechniques Sub-Project 4: A combination of animalmodels,insituhybridization andproteomics Sub-Project 5:MRI and clincal diagnosis upon treatment with L-Dopa Sub-Project 2: Uncover novel pathwaysforneuropathies Sub-Project3:Assistthediagnosis ofmusculardystrophies Sub-Project 4: Uncover novel mechanisms of neural tube developmentandpossibletherapy forNeuralTubeDefects Sub-Project 5: Assist in the diagnosis of pain-related symptomsinPD Sub-Project6:Populationsurvey Sub-Project 6: Assist in the destigmatisation of epilespy and suggest approaches to help suffererscope Sub-Project 7: Clinical diagnosis andneuroimaging Sub-Project 7: Assist in the diagnosisandtreatmentofangiitis Sub-Project 6: To determine the levelofsocialstigmainepilepsy Sub-Project 8: A combination of molecularbiology,geneexpression andclinicaldiagnosis Sub-Project 7: To determine the associationbetweenAngiitisinTB meningitis Sub-Project 9: A combination of clinical diagnosis and immunologicaltests Sub-Project 8: Determine predictors of ischaemic stroke in young patients with hypertension anddiabetes Sub-Project 8: To investigate the potential of microRNAs as novel biomarkersforclinicaldiagnosisin ischaemicstroke Sub-Project 10: A combination of clinicaldiagnosis,pharmacological tests and kinetic modeling of parameters Sub-Project 5: To perform brain imaginginParkinson’sdiseaseand related disorders to understand thediseaseprogression Sub-Project9:Tounderstandmore aboutautoimmuneencephalitis Sub-Project 9: Assist in the diagnosis and treatment of autoimmuneencephalitis Sub-Project 10: to construct dosing recommendations for phenytoin, sodium valproate and midazolam in renally impaired patientsforthetreatmentofstatus epilepticus Sub-Project 10: To determine the pharmacokinetic profile of lamotrigine in patients with renal impairment using a modeling and simulationapproach HIR Annual report 2011.indb 56 24/05/2012 9:44:52 High Impact Research Annual Report 2011 Possible High Impact Journals forPublications LancetNeurolgy PLosOne Collaborators UniversityofSussex,UK UniveristyofSydney,Australia PLosMedicine University of London, UK and UniversityofBristol,UK American Journal of Human Genetics The Royal Melbourne Hospital, TorontoWesternHospital PNAS UniversityofMelbourne,Australia BrainResearch University of Auckland, New Zealand ClinicalPharmacology 57 Therapeutics Project No: UM.C/625/1/HIR/MOHE/MED/09 Title: Characterization of Epitopes on the Merozoite Surface Antigens of Zoonotic Simian Malaria Parasite Principal Investigator : Professor Dr. Fong Mun Yik Faculty : Department of Parasitology, Faculty of Medicine SummaryofResearchProposal Four species of the blood parasite Plasmodium are responsible for human malaria:Plasmodium falciparum,P. vivax,P. malariae,andP. ovale.Zoonotic infectionsbymonkeymalariaparasiteshaveinitiallybeenthoughttoberare. However,in2004,alargefocus(101cases)ofhumanP. knowlesi(amalaria parasiteofmacaquemonkeys) infectionwasreportedintheKapitDivisionof Sarawak.Morerecently,theInstituteforMedicalResearchreported55.9%of humanbloodsamplesreceivedwaspositiveforP.knowlesi. Themerozoitesurfaceproteins(MSPs)ofPlasmodiumarecrucialmolecules involvedintheinvasionoftheparasiteintoitshosterythrocytes.Anti-MSP antibodies are detected in malaria patients. Also, these antibodies from individualsthatareclinicallyimmunetomalariainhibitinvasionofPlasmodium merozoitesintoerythrocytes.Therefore,mappingtheepitopesontheMSPs canprovideusefulinformationforimmunodiagnostics,immunotherapy,and vaccinedevelopmentagainstmalaria The antigenicity of MSPs of P. knowlesi has yet to be fully elucidated. InvestigationontheimmuneresponsesthatareevokedbytheseMSPswill provide knowledge on the type of immune protection against P. knowlesi. In this respect, the immune response evoked by P. knowlesi MSPs will be comparedwiththatofitsclosestrelatedhumanmalariaspecies,P. vivax. Objectives Methodology (i) Identify and characterize epitopesonthemerozoitesurface proteinsofPlasmodium knowlesi (i) The methodology involves cloning and expression of recombinant P. knowlesi MSPs, construction of phage display library, determining binding specificity of the selected phage by ELISA, cloning and DNA sequencing of selected phage, and locating the epitopes using bioinformatic and structural biologytools. (ii) To characterize immune responsesevokedbyPlasmodium knowlesiin vivo and in vitro. knowlesi and P. vivax MSP recombinant proteins, purification of the recombinant proteins, and immunological study of the recombinantproteinsusingmouse modelandinvitrosystem (ii) The methodology involves cloning and expression of P. HIR Annual report 2011.indb 57 24/05/2012 9:44:52 58 High Impact Research Annual Report 2011 Outcome Localization of epitopes on immunologically important merozoite surface proteins of Plasmodium knowlesi. Immunogenicityofthesemerozoite surface proteins Possible High Impact Journals forPublications InternationalJournalofParasitlogy JournalofClinicalMicrobiology EmergingInfectiousDiseases MalariaJournal Collaborators Dr Lau Yee Ling, University of Malaya Dr. Laurent Renia, Laboratory of Malaria, Singapore Immunology Network,A*Star Dr. Bruce Russell, Laboratory of Malaria, Singapore Immunology Network,A*Star Dr Chao Day-Yu, National Chung HsingUniversity, Project No: UM.C/625/1/HIR/MOHE/MED/10 Title: A Study of Brain Signal Modulation Among Methadone Maintenance Clients Receiving an Adjunct Acupuncture Treatment in UMMC Principal Investigator : Professor Dr. Mohamad Hussain Habil Faculty : University of Malaya Center of Addiction Sciences (UMCAS), Faculty of Medicine SummaryofResearchProposal UniversityofMalayaCenterofAddictionSciences(UMCAS)isthenewlyset up center of excellence for the University of Malaya. It is timely as current availablefacilitiesinthemainhospitalareoverutilizedandnolongerableto supporttheincreasingnumberofclients.Themainfocusofthesecentersare generatingresearch,aplatformfortrainingprogramsandofferingintegrated treatment services in addiction field plus infectious disease related to substancesuse. ThereisahighprevalenceofHIV/AIDScasesreportedandillicitsubstances used in Malaysia with widespread injecting practices and sharing needles among drug users. It is estimated about 80% of 70,000 HIV/AIDS cases notificationduringyear2006areamongIVDUs.Thegovernmenthasstarted aharmreductionprogramsinceOct2005involvingmethadonemaintenance treatment(MMT),needleandsyringesexchangeprogram(NSEP)andcondom distributionamongdrugusers.Theresultsarepromisingwhereby84%the retentionrateofclientsintreatmentwithinoneyear.Moreover,itwasreported that there is a reduction of overall drug use, crime rates and a recidivism and HIV risk behaviors. In addition, there are higher employment rate and better quality of life. However, low numbers of addicts are receiving MMT treatment.EvenlowernumberofHIV+addictsreceivedARVtreatment.There is s widespread belief among health providers that heroin addicts are not compliantwithARVandposeriskofmulti-drugresistancecases.However, many studies have shown that HIV+ heroin addicts stabilized on Drug Substitution Therapy (DST) have better compliance toward Anti-Retroviral (ARV) treatment and equal success rate as compared to non-drug related HIV+.Malaysianleaderhasdeclaredtheyear2015asadrugfreenation.So, thereisaneedformorenumberofHIV+addictsreceivestreatmentinorderto givebetterimpactsonHIVprevalencereductioninthecountry. ApparentlythereisalowcoverageofMMT/ARVamongaddictsandsofar, only 5000 addicts received methadone treatment in government setting. Thereispossibilityoffailureinachieving25,000addictsonDSTby2015as targetedbythegovernment.Thiscanaffectourvisiontobecomeadeveloped nationin2020asWHOrequirementatleast20%HIV+onARVtreatmentfor adevelopednation.ThepossibilityofMethadone-ARVdruginteractionsare commonanddifficulttomanageandsometimeslifethreatening.So,thereis aneedforintegratedHIVandaddictiontreatmentservicestocaterforthis marginalizedsociety. HIR Annual report 2011.indb 58 24/05/2012 9:44:52 High Impact Research Annual Report 2011 59 Electroencephalogram(EEG) has the potential to become an effective tool for measurement of improvement of patients in a more objective way that reduces the requirement of traditional ways which need assessment from already exhausted clinicians using time consuming and non standardized methods.ThisresearchhasthepotentialtobepublishedinISIcitedjournal because addiction has become a niche area as discussed in various high impactjournals,andshowninvarioussearchenginese.g.OvidSP,Pubmed andSciendirect. Acupuncture has been used by Chinese ancestors to treat various medical illnesses including neurological and psychiatric disorders. In China, the acupuncturetechniqueswerepracticedwidelyeventhoughthemechanisms andhowitworkedareunclear.Acupunctureproceduresdoworkforcontrolling pain,vomitingsecondarytochemotherapy,etc.Mostliteraturessupportthe efficacyofacupunctureasanadjuncttherapyforexistingtreatmentbutnot asastandalonemodality.Manyacupuncturepractionersclaimacupuncture therapy has benefits for various addiction problems. However, apparently there was not enough evidence based study to support the effectiveness of acupuncture treatment on any addictive disorders. Literature review and meta-analysisgavemixedopinionsontheeffectivenessofacupunctureinthe treatmentofaddictivedisorders.Manystudiesthatsupporttheeffectiveness of acupuncture in the treatment of addictive disorders are lacking in terms ofdesign,sampleandoriginatedfromEasternscientists,themajorityofthe studiesareinconclusiveduetopoordesign,andlackofsamples.Moreover, thestudiesonlyfocusonreducingthewithdrawal(detoxification)ratherthan longtermoutcomes.Atthemoment,addictiondisordersitselfisregardedasa chronicrelapsingbraindiseaseassupportedbymanystudies.Detoxification loneisnottheonlyindicatorforeffectivenessoftheinterventionsbutthelong term outcomes should also be considered. For example, even methadone when given only for detoxification, showed failed results where majority of thepatientsgobacktodrugsagainwhenthemethadonetaperoff.However, when methadone was given for long term (maintenance therapy), the patients showed improvement n every aspects of their life and maintained their functioning status. However, the effectiveness of acupuncture as an adjunctformethadonetreatmentwasstudiedandtheresultsshowedsome benefit on reduction of withdrawal state but not for long term outcomes. Auricularacupunctureiswidelypracticedinthetreatmentofvariousaddictive disorders. Sofar,evensubstanceslikealcoholandnicotineaddictionwerestudiedand debatedbutinconclusive.However,AmphetamineTypeStimulants(ATS)have rarelybeenexploredprobablybecauseitisnewinthemarket.InMalaysia,the prevalenceofopiatesisincreasingandmethadonetreatmenthasbecomea goldstandardtreatment,whereasATS,e.g.amphetamine,metamphetamine and ecstacy (MDMA) dependence syndrome is even more problematic. The prevalence of ATS misuse is exponentially increased especially among youngerdrugusers.However,therewasnoevidencebasedpharmacological interventionsofar.Thetreatmentmainlyreliesonpsychosocialinterventions withlowsuccessrate. Objectives Methodology To investigate the role of acupuncture as an adjunct treatment for opiate dependents individuals. Thisisaprospective,open-labeled, parallel, randomized- controlled trial comparing two arms,an acupuncture group as adjunct therapy for opiate dependents receivingmethadonemaintenance therapy(MMT) versus standard care(MMT alone) group. The new brain - emerging technique, an electroencephalogram (EEG) will be used in monitoring the brain signal modulation changes overtimeasaresultofacupuncture and methadone treatment. The clinicalassessmentandstructured questionnaires e.g. opiate To investigate the role of encephalogram (EEG) as new brain-emerging technique in objective monitoring of the effectiveness of various treatment optionsforopiatedependents HIR Annual report 2011.indb 59 treatment index (OTI), Drug and HIVriskbehaviors,retentionratein treatment, crime rate, rapid urine drugstestandWHOqualityoflife willbeusedasstandardoutcomes measurement in comparison to EEG Outcomemeasures: • Retention rate in treatment for3months • Withdrawal severity: Clinical Opiate withdrawal scale(COWS)-atbaseline,1 week,twoweeks,6weeks and12weeks: 24/05/2012 9:44:52 60 High Impact Research Annual Report 2011 • HIV risk behavior, crime rate and Opiate/other illicit substance use: Opiate treatment Index (OTI) - baselineand3months • Quality of life: WHO QoL- Baselineand3moths • Urine drug status: Rapid urinedrugtestkit(5inone test kit: Opiates, MDMA, Metamphetamine, Canabis, Benzo) - twice weekly duringinductionperiodand weeklytill3months • Brain signal modulation: EEG monitoring machine- at baseline, 1 week, two weeks, 6 weeks and 12 weeks: Outcome Fromthisstudy,weexpecttocome outwithevidenceofeffectiveness of acupuncture as an adjunct towards current methadone treatment. We also hope to find outtheassociationofEEGpattern with acupuncture and methadone treatment. We would like to use quantativeEEGasmonitoringtool for progress of methadone and acupuncture treatment for heroin addictsinfuture.Ofcoursebythe endof1-5years,wewouldliketo publishatleast5ISI/WoSor3tier onepapers Possible High Impact Journals forPublications JournalofsubstancesUse Lancet Nature AcupuntureandElectrotherapeutic research Actanewpsychiatrica Collaborators KlinikDrKahfidz,Kajang KlinikFamilySriPetaling,Petaling Jaya Project No: UM.C/625/1/HIR/MOHE/MED/11 Title: Molecular Investigation of Disease Mechanisms Principal Investigator : Professor Dr. Mary Anne Tan Jin Ai Faculty: Department of Molecular Medicine, Faculty of Medicine SummaryofResearchProposal Molecularinvestigationandtechniquesinmolecularbiologyhavebeenapplied acrosstheboardinvariousfieldsofmedicineanddisease.Thetechniques and protocols developed are rapid sensitive and specific for not only the diagnosis of genetic disorders, but also for investigation into nutrigenomic, antivancerandnaturalproductresearch. Objectives Methodology To develop molecular techniques thatcanbeutilizedingeneticand pathologicaldisorders Laboratory protocols began with the collection of tiger milk mushroomandleavesofOcimum canumandPlectranthus ambonicus leaves.Inaddition,differentstrains of Vibrio cholearae strains were identified and subtyped. As this HIRprojectsinvolvedinvestigators withdifferentsub-projects,various methodologies specific to each sub-project were carried out. The majortechniquesemployedwere: To carry out genomic research on natural products specifically in the identification of antiviral and cytoxicsubstances Genotyping of bacterial genes in humandisease HIR Annual report 2011.indb 60 1. Geneexpressionstudies 2. Shot-gun analysis of snake venoms 3. Extraction assays for plant productsandbacteriaDNA 4. Cytoxic and antioxidant assays to identify the natural bioactive substances and naturalplantproducts 5. Multilocus Sequence Typing (MLST) and Multivirulent Locus Sequence Typing (MVLST) for bacterial subtyping Outcome The sub-projects have produced important and informative results and data. Genomic, proteomic andantioxidantinvestigatorshave producedthefollowingoutcomes: 1. Effect of velvet bean pretreatment on cobra venom-induced gene expression changes completed and data analysis ison-coing 2. Venomglandsofseverallocal venomous snakes are in the process of transcriptome analysisbyBGI 24/05/2012 9:44:52 High Impact Research Annual Report 2011 3. 4. The antioxidant activities of bioactive substances from tiger milk mushroom have beencompleted Essential oils from the plants Ocimum canum and Plectranthus ambonicus have beenextracted 5. Anti-carcinogenic properties of Ocimum canum against hydrogen peroxide induced DNAdamage 6. Mouse fibroblast cells pretreated with various concentrations of essential oils showed lower rate of DNAdamage 7. An association between 2245GA allele of the RAGE (Receptor for Advanced Glycation End-products) gene and development of diabetic retinopaty\hy was established 61 Collaborators NationaluniversityofSingapore UniversityofSiena,Italy UniversityofJos,Nigeria Possible High Impact Journals forPublications Journal of Biomedicine Biotechnology QueenSaobhvaMemorialInstitute, Thailand and MolecularBiologyandEvolution JournalofBiologicalSciences Comp.Biochem.Physiol. Ethanopharmacology GenesandNutrition Project No: UM.C/625/1/HIR/MOHE/MED/12 Title: Research on Cancers in Malaysian Patients: Improving Survival through Innovation and Collaboration Principal Investigator : Profesor Dr. Hany Ariffin Faculty : University of Malaya Cancer Research Institute (UMCRI), Faculty of Medicine SummaryofResearchProposal Thisprojectisanamalgamationofseveralstudiesaimedtowardsimproving thesurvivalratesofMalaysiancancerpatients.Toachievethisgoal,UMCRI have made several initiatives to develop innovative treatment methods, capitalizingonadvantageouscollaborations.Thepaediatriconcologyunitfor instance,incollaborationwithNationalUniversityofSingaporehasembarked on a treatment protocol to optimize the use of vincristine, a common chemotherapy drug via better understanding of its pharmacokinetics and individual patient response. Collaborative efforts have allowed tapping into theexpertiseofinstitutionsabroadsuchastheUniversityOfSouthampton, UKbythegynaecologicalcancerunittodevelopnanoparticle-basedtherapy. In addition, UMCRI acknowledges the importance of excellent laboratory infrastructure and support. Hence, it is developing a tumour tissue bank, cytogeneticserviceaswellascellcultureandanimalfacilities. Objectives To better understand biology and treatment response in childhood acute lymphoblastic leukemia patients to ensure accurate therapeutic stratification with minimallong-termside-effects Tostudymismatchrepairproteins in hereditary non-polyposis colorectalcancer To study prevalence of BRCA1 and BRCA2 in Malaysian ovarian cancerpatients HIR Annual report 2011.indb 61 To develop nano-particle based therapy for endometrial cancer andosteosarcoma To develop a high-quality tumour tissue repository and database system Methodology andOutcome Paediatric Oncology (Acute LymphoblasticLeukaemia) TheMalaysia-Singapore(Maspore ALL 2010) trial has accrued patients since July 2011. To date, 16denovoALLpatientshavebeen recruited. All these patients have complete clinical and laboratory data and nearly all have had their diagnostic bone marrow samples banked ColorectalCancer Thecolorectalteamhasembarked on a study related to Hereditary Non -Polyopsis Colon Cancer (HNPCC), a hereditary cancer characterized by the risk of developing multiple types of 24/05/2012 9:44:52 62 High Impact Research Annual Report 2011 cancer including colorectal and endometrial cancers. The team will be screening mismatch repair (MMR) protein expression by immunohistochemistry (IHC) in the tumour samples of selected colorectalandendometrialcancer patients who are identified as at high risk of developing HNPCC. The MMR protein expressions and clinicopathological features of these patients will be then attributed and compared with the established features of HNPCC in otherpopulation GynaecologicalCancer The prevalence study of BRCA1 and BRCA2 in ovarian cancer in collaboration with CARIF is ongoing. 359 patients have been accrued. In the HPV genotyping research project, 100 subjects havebeenrecruited Under the collaborative research with CARIF, we have found that 15% of endometroid and highgrade serous ovarian cancer are BRCApositive.Ourovariancancer cohort has also been enrolled into an international consortium (OCAC). In the HPV genotyping project,15%ofthesubjectswere HPV-positive with 10% of these patientscarriedhigh-risk(HR)HPV Cytogenetics Cytogenetic analysis is part of routine clinical practice as an essential tool in diagnosis and prognosis of blood cancers. Nearly 200 patients with leukemia /lymphomahavebeenkaryotyped and the success rate for the cell yieldismorethan90%.FISHand molecular screening of oncogene fusion transcripts methods have alsobeenestablished TumourTissueRepository UptoOctober2011,1254tumour tissuesamplesfrom192consented patientswithvariousmalignancies have been catalogued and cryopreserved Possible High Impact Journals forPublications British Journal of Obstetrics / Gynaecology ProcNationalAcademyScience JournalofClinicalOncology LancetOncology NatureGenetics Collaborators Prof Sjoerd van der Burg, Leiden University Medical Centre, Netherlands Dr Sathibalan Ponniah , Cancer Vaccine Development ProgramUnited States Military CancerInstitute,Bethesda,USA Prof Allen Yeoh, Paediatric Oncology, National University of Singapore Dr Cheong Yin Ching , Gynaecological Oncology, UniversityofSouthampton Dr Toh Han Chong , National CancerCentre,Singapore Prof Gunaretnam Rajagopal, CancerInstituteofNewJersey Project No: UM.C/625/1/HIR/MOHE/MED/13 Title: The use of acute phase reactant proteins as cancer biomarkers Principal Investigator : Professor Dr. Onn Hashim Faculty : Department of Molecular Medicine, Faculty of Medicine SummaryofResearchProposal Early detection of cancer could possibly improve the success of treatment in patient. Currently, there are many cancer biomarkers that can be used asdiagnostictool.However,mostofthebiomarkershavelowerspecificity andsensitivityanddiagnosisisonlypossibleatalaterstageofthecancer. Acute Phase Reactant Proteins (APRPs) have been found to be associated withmanycancers.Theaberrantexpressionoftheseparticularproteinscan be useful as potential biomarkers to detect the cancer at earlier stage. In previous studies, many of these APRPs were identified through proteomic profiling.However,thistechniquehasitslimitationsandweakerreproducibility aswellaslowerreliabilityinquantification. Inthisstudy,wewillfocusonthemultipledetectionofAPRPssimultaneously to find potential biomarker(s) fingerprint for various types of cancer using proteinarraysystem.Proteinarraysystemdetectsthedifferentexpressionof thedesiredproteinswiththehelpofspecificantibodies. HIR Annual report 2011.indb 62 24/05/2012 9:44:52 High Impact Research Annual Report 2011 Objectives Methodology Outcome To profile the serum APRPs of different groups of patients with cancer using protein array technology Serum from patients with breast cancer, gyneacological cancer, bone cancer, prostate cancer and healthy control will be collected fromUniversityofMalayaMedical Center(UMMC).Theserumwillbe subjectedtoproteinarrayanalysis to detect the level of APRPs. Briefly,specificprimaryantibodies will be coated on customized protein array chip. The primary antibody will selectively capture the protein in serum sample and florescent labeled secondary antibody will be introduced to the bound protein. The protein arrayslidewillbescannedforthe florescence signal in microarray scanner.Intensityofeachprotein willbecomparedbetweencontrol and disease group to identify the potential biomarkers through statistical analysis. Validation will be performed on multiple immunoassay system and both detection methods of multiple protein expression will be evaluatedtofindthemostreliable andeffectivemethod The protein array method should perform better in identifying large number of different proteins in a singlerun Toanalysethedataobtainedusing imageanalysissoftwareinorderto compare APRP profiles between patients with different types of cancerandcontrolcohorts To characterize APRP in different groups of patients with cancer in accordance to their stages of cancer, tumor load and treatment andperformancestatus To validate the APRP expression using multiplex ELISA and gene microarray To differentiate key biomarkers (prognostic/diagnostic)fordifferent cancers which can be utilized for clinicalmanagement 63 We expect to find aberrantly expressedAPRPSincancerserum ascomparedtocontrolwhichcan beusedaspotentialbiomarkers Possible High Impact Journals forPublications Electrophoresis JournalofProteomeResearch JournalofProteomics Proteomics Molecular&CellularProteomics Collaborators Professor Emeritus Dr Veer Bhavanandhan (Pennsylvania State University, United States of America) Professor Dr Richard Cogdell (University of Glasgow, United Kingdom) Project No: UM.C/625/1/HIR/MOHE/MED/14 Title: Spatio-Temporal Modelling and Meta-analysis (STeMM) Principal Investigator : Professor Dr. Awang Bulgiba Awang Mahmud Faculty : Department of Social and Preventive Medicine, Faculty of Medicine SummaryofResearchProposal Infectiousandnon-infectiousdiseasesrepresentthedoubleburdenofdisease whichMalaysiafacestoday.Withveryfewmodelswhichcanbeappliedto thesediseases,ourpublichealthmanagementisverymuchahit-and-miss affair. The STeMM Porgramme will develop the first spatio-temporal model for an infectious disease in Malaysia as well as the most comprehensive cardiovascular models for use in Malaysia. This programme will also provide the most comprehensive meta-analysis on infectious diseases and cardiovasculardiseasesinMalaysia. Methodology Objectives Todevelopthefirstspatio-temporal modelforanydiseaseinMalaysia which combines geographical location, time-dependent data, geneticandenvironmentaldata HIR Annual report 2011.indb 63 To model cardiovascular and relateddiseasesforuseinMalaysia To perform and provide the most comprehensive metaanalysis on infectious diseases and cardiovascular diseases in Malaysia Data will be collected from various sources, including the Meterological Department, national registries, hospitals etc tobeusedinthesemodels.Using thesedata,modelswillbecreated usingtheSTEM,Stata,SPSSand othersoftware 24/05/2012 9:44:53 64 High Impact Research Annual Report 2011 Outcome This programme will result in a better understanding of the dynamics of infectious disease spread as well as factors related to the changing patterns, dynamics and related factors of non-infectious disease spread in Malaysia. This will enable better preparedness for outbreaks as well as the formulation of public health policies in Malaysia. These have the potential to result in the modification of Clinical Practice Guidelines, development of new risk scores for cardiovascular diseases, Public Health data sharing with neighbouring countries to fight infectious diseases and the establishment of the first Cochrane Centre in Malaysia Possible High Impact Journals forPublications JournalOfInfectiousDiseases EmergingInfectiousDiseases ClinicalInfectiousDiseases CardiovascularResearch PreventiveMedicine CochraneReviews HeartBMJ Collaborators Prof. Dr. Cuno S.P.M. Uiterwaal, UniversityMedicalCentreUtrecht, Netherlands Prof.Dr.ArnoW.Hoes,University Medical Centre Utrecht, The Netherlands Prof.Dr.PrathapTharyan,Christian MedicalCollege,India Prof. Dr. Nico Nagelkerke, United ArabEmiratesUniversity Prof.Dr.RobertGrahamCumming, UniversityofSydney Dr.BrianBuckely,CochraneFellow Project No: UM.C/625/1/HIR/MOHE/MED/15 Title: Shared Equipment for the Faculty of Medicine (Central Facility) Principal Investigator : Dr Puteri Shafinaz Akmar Abdul Rahman Faculty : Department of Molecular Medicine, Faculty of Medicine SummaryofResearchProposal TheHealthandTranslationalMedicine(HTM)Clusterhasset-upafewcore centralfacilitieswithintheFacultyofMedicine. Eachofthecentralfacilities also functions as a research centre and is currently engaged in research in specialisednicheareassuchascancerproteomicsandgenomics,infectious diseases, pharmacological studies and drug discovery. In line with HTM’s vision to be a top class research entity, the centres have to be equipped with the state-of-the-art equipment for the advancement of research in the UniversityofMalaya. The research instruments proposed for purchase are essential for the discoveryprocessinproteomics,glycomics,stemcell,moleculargenomics andpharmacologicalresearch. Uponpurchaseoftheequipment,theywillbe designatedascentralfacilityandcanbeutilisedbyscientistsfromwithinthe FacultyandUniversityinvolvedinsimilarresearchareas. List of Equipment for Central Facility (2011): UM/MoHE High Impact Research Grant Allocation(HIRGA) 2-Dimensional Gel system and ImageAnalysissoftware InVivoImagingSystem Short Fragment Sequencing and AnalysisSystem VacuumConcentrator HighResolutionUltrasonography CellSorterforFlowcytometry RealTimeCellAnalyser HIR Annual report 2011.indb 64 Refrigeratedcentrifuge RTPCR(4units) Sonicator Freezers 24/05/2012 9:44:53 High Impact Research Annual Report 2011 ExpectedOutcome The availability of these state-ofthe-art instruments placed under sharedresearchfacilitywillfurther enhancetheabilityofourscientists toperformresearchthatisatleast on par with those performed by internationally renowned research groups. This will translate into a significant increase in the number of published research papers from our Faculty in internationally renownedjournalswithhighimpact factor. The increased number of goodpublicationswillalsobenefit theUniversityofMalayaintermsof rankingandworldwiderecognition Possible High Impact Journals forPublications InternationalJournalofCancer Evidence-based Complementary andAlternativeMedicine JournalofInfectiousDiseases American Journal of Tropical MedicineandHygiene BiochemicalPharmacology American Medicine MolecularEndocrinology Journal of Sports 65 JournalofProteomeResearch EmergingInfectiousDiseases BritishJournalofNutrition Cellular And Molecular Life Sciences BritishJournalofCancer InternationalJournalofParasitlogy JournalofProteomics JournalofClinicalMicrobiology PlosOne,IF4.351 JournalofOrthopedicResearch Electrophoresis JournalofBiologicalChemistry JournalofMedicinalChemistry Project No: UM.C/625/1/HIR/MOHE/MED/16 Title: Beijing Genomic Bioinformatic Services) Institute (Genomics and Principal Investigator: Professor Dr. Fong Mun Yik Faculty : Department of Parasitology, Faculty of Medicine SummaryofResearchProposal Project 1: Acinetobacter baumanii is a major health threat to immunocompromisedandlong-termedin-dwellinghospitalpatients.Ithasacquired multiplyantibioticresistancepropertiesiscommoninmosthealthcarefacility. Wenowneedtosequencethewholegenomeofthebacteriatodiscoverthe genesthatconfertheresistanceproperties. Project2:Cancerisageneticdiseasehashadprofoundinfluenceincancer therapeutics.Comparingsubsetsofsingleprimarycancersieoriginaltumor withmetastasesandxenograftmodelswillallowtheunderstandingofhow cancer genomes evolve with time or whether metastases originate from a subsetofcancercellshavingstem-cellproperties. Project3:Obesityisachronicdisorderthatcanincreasetheriskofdeveloping type2diabetesmellitus,coronaryheartdisease,hypertension,asthma,sleep apnoea, osteoarthritis and certain types of cancers. The Malaysian Non CommunicableDiseaseSurvey(NCD2005)reportedthat48.6%ofadultsin Malaysiaareobese.Theprevalenceofchildhoodobesityhasbeenincreasing at an alarming rate. Variation in certain genes has been associated with obesity,BMIandfatmasspercentageinchildrenandadults(Wuetal.,2010). Thisstudyisproposedtodeterminethementionedgeneticpolymorphismin themultiracialpopulationinMalaysian Project4:Wehaveseenincreasingprevalenceofzoonosismalaria,filariasis and toxoplasmosis in this region. Further investigations into the genetic basis of these parasite strains and the mechanisms that profoundly alter transmissibility and virulence will provide a greater understanding of the evolutionofthediseasesandglobalparasiticdiseaseingeneral HIR Annual report 2011.indb 65 24/05/2012 9:44:53 66 High Impact Research Annual Report 2011 Objectives Methodology To undertake full genome resequencing of two Acinetobacter baumanii isolates and gene sequencebioinformaticsanalysis Samples will be collected and genomic DNA will be extracted. The genome sequencing and analysiswillbeperformedtogether withthecollaboratorsformBeijing Genome Institute. Activities in BGI include: library contruction, sequencing(200bp,500bp,800bp, 2kb, 5kb, 10kb and 20kb insertsize), assembly, annotation and evolutionanalysis To understand how cancer genomes evolve with time, whethermetastasesoriginatefrom a subset of cancer cells having stem-cellproperties To identify the complex diseasesrelated genetic variations (SNPs, CNVset al.)associatedwithadult and childhood obesity through a genomewideassociationstudy To sequence the full genome of Anopheles cracens To re-sequence and analyze the genomeofP. knowlesi TosequenceP. knowlesireceptors genesininfectedpatient To sequence the Whole genome of Toxoplasma gondii RHstrain,B. Pahangi and otherparasites Outcome Two full genome sequence of Acinetobacter baumanii for the antibioticresistantandsusceptible strains Determination of the genetic/ environmental drivers for cancer initiationandprogression Development of novel targeted therapyforcancer Technology transfer to UM in the formofcanceranimalmodelling Theprimaryaimoftheresearchis to identify the complex diseasesrelated genetic variations (SNPs, CNVset al.)associatedwithadult and childhood obesity through a genomewideassociationstudy Full genome sequence and complete genetic information of Anopheles cracens,P. knowlesi, B. Pahangi andT. gondii Possible High Impact Journals forPublications NatureBiotechnology GenomeBiology GenomeResearch Science Collaborators SazalyAbuBakar Prof.Dr. HanybintiMohdAriffin Prof.Dr. ZahurinbintiMohamed DrLauYeeLing BeijingGenomeInstitute Project No: UM.C/625/1/HIR/MOHE/MED/17 Title: Targeted Delivery of Antineoplastic Photoactive Compounds and Peptides Principal Investigator : Professor Dr. Chung Lip Yong Faculty : Department of Pharmacy, Faculty of Medicine SummaryofResearchProposal Cancer is the second major life threatening disease in the world and the common cancer treatment modalities such as chemotherapy and radiotherapy often inflict adverse effects to patients. New photosensitizer basedphotodynamictherapy(PDT)andanticancerpeptidebasedtreatments havebeenproposedtoprovidebettertreatmentoutcomewithlesseradverse effect.However,theinherentweaknessesofphotosensitizersandanticancer peptidesthataffectefficientdrugdeliveryoftenlimittheirdevelopmentand useinclinicalsettings. ToovercomethechallengesofdeliveryofPDTandpeptidedrugsinvivo,the drugs may be modified by conjugating or entrapping them to water soluble biocompatiblepolymers.Modificationofthephotosensitizer’spharmacokinetic properties via polymer-drug conjugation approach may increase the water/ blood solubility, reduce in vivo random dissemination and non-specific cytotoxicity, and promote the targeting of photosensitizer to the tumour via enhanced-permeability-retentioneffect.Foranticancerpeptides,encapsulation by biopolymers may improve their protection against degradation by low gastric pH and enzymes, providing a controlled release of the entrapped macromolecules and hence increase the bioavailability and pharmacological efficacyoftheanticancerpeptideswhengivenviatheoralroute. HIR Annual report 2011.indb 66 24/05/2012 9:44:53 High Impact Research Annual Report 2011 Objectives Methodology The objective of the study is to explore the possibility of applying polymer-drug conjugation and a polymer based intestinal sustained drug delivery approach to improve the antitumour efficacy of photoactive drugs and anticancer peptides. This is based on the hypothesis that conjugation of photoactive drugs onto a suitable polymeric carrier such as polyglutamic acid, and inclusion of anticancer peptides ontoasuitableintestinalsustained drug delivery system may help to improve the bioavailability, in vivo pharmacokinetics and tumour targeting properties, and thus in vivo antitumour efficacy of photoactive drugs and anticancer peptides Polymer-drug conjugates will be synthesized chemically or physically by combining biopolymers with selected photoactive drugs or anticancer peptides, and characterized using physical and chemical methods. The conjugates will be tested for stability and drug release profiles inwaterandblood,andtheinvitro cytotoxicity using human/animal cancer and normal cell lines. The conjugatesthatshowgoodstability and enhanced in vitro anticancer properties will be further tested in murine tumour model and the chick chorioallantoic membrane (CAM) model to evaluate their in vivo toxicity, antitumour effects andbiodistributionprofiles compounds or peptides. The polymer-drug conjugates developed may potentially be translated into clinically useful anticancer compounds with improved drug delivery and targeting properties, and hence increasedrugefficacyandreduce non-specifictoxicity Possible High Impact Journals for Publications JournalofBiologicalChemistry JournalofMedicinalChemistry JournalofControlledRelease CarbohydratePolymers Biomaterials Collaborators Outcome Novel methods and new knowledge/experience in conjugating photoactive compounds to polymers and encapsulation of peptides for oral delivery will be obtained. This approach will improve the pharmacokinetics, tumour targeting and reduce the nonspecific toxicity of photoactive HIR Annual report 2011.indb 67 67 Kiew Lik Voon (Co-Principal Investigator), Mohamed Ibrahim Noordin, Faculty of Medicine, University of Malaya, Kuala Lumpur,Malaysia LeeHongBoon,CancerResearch Initiative Foundation, Subang Jaya,Malaysia Kevin Burgess, A&M University, Texas,USA 24/05/2012 9:44:53 68 High Impact Research Annual Report 2011 RESEARCH PROPOSAL (HIR-MoHE5Years) FacultyofEngineering Project No: UM.C/625/1/HIR/MOHE/ENG/01 Title: Precision Joining Technology Principal Investigator : Professor Dr. Mohd Hamdi Bin Abd Shukor Faculty : Department Engineering Design & Manufacture, Faculty of Engineering SummaryofResearchProposal Theresearchthemeofadvancedjoiningtechnologyencompassesthetopics on soldering, brazing and welding. Advances in these joining technology has produced significant results which has direct industrial applications, in particular, the semiconductor industry. The drive to find environmentally friendlysolutionshasledtotheintenseresearchactivitiesintopicssuchas theutilisationoflead-freesoldercompositionoflatestgenerationmicrochips. In addition, the ever increasing demand of precision joining, especially in emerging areas of microfabrication, extreme operating conditions of high performancecomponentssuchasinaerospaceandaeronauticalsubsystems and critical areas of medical and surgical apparatus development has led to the need for newer materials and better processing techniques. Thus, withtheserequirementsinmind,thisresearchproposalispresentedforthe purpose of establishing a strong fundamental and cutting edge research presence in the area of precision joining technology in Universiti Malaya. Amongsttheproposedareasofresearchare: Objectives To evaluate the physical, mechanical and joining characteristics of selected advanced semiconductor and uniquematerialspairs To evaluate the microstructural and compositional properties of theselectedmaterialcombinations To comparatively evaluate the joiningperformanceoftheselected materialcombinations Methodology This project will strengthen the fundamental knowledge required in the field of precision joining technology and to explore new material combinations and HIR Annual report 2011.indb 68 i. Microscale joining of dissimilar materials by friction stir welding technique. ii. Precision joining of materials for high performance underwater applications. iii. Evaluationofmicroscalespotjoiningtechniquesvialaserwelding. processing techniques. Parallel sub-projects will encompass a wide range of research scope within the research field including computational and mathematical modelling, simulation, and laboratoryexperimentalwork.The major focus of the research is on thecharacterisationofnewjoining techniques for selected advanced seminconductors and uniqe materialpairs Outcome No. of Tier 1 Publications Expected:37 Possible High Impact Journals forPublications JournalofAlloysandCompounds (ImpactFactor:2.135,Tier1) InternationalJournalofEngineering Science(ImpactFactor:1.360,Tier 1) Science and Technology of Welding and Joining (Impact Factor:1.327,Tier1) MaterialsCharacterization(Impact Factor:1.416,Tier1) Metals and Materials International (ImpactFactor:1.090,Tier1) Collaborators Professor Emeritus Dr. Tadashi Ariga,Japan 24/05/2012 9:44:53 High Impact Research Annual Report 2011 69 Project No: UM.C/625/1/HIR/MOHE/ENG/02 Title: Synthesis of Blast Resistant Structures Principal Investigator : Professor Ir. Dr. Mohd Zamin Jumaat Faculty : Department of Civil Engineering, Faculty of Engineering SummaryofResearchProposal The increase in recent terrorist attacks is one of the factors that led to a greaterinterestinresearchworksinblastresistantstructures.Theformation of concrete shrapnel and how they were spread about during a blast were generallyidentifiedasthemainfactorswhichresultedinseriouswoundand fatalities.Failureofnormalconcrete(NC)toabsorbimpactenergyleadstothe creationoftheseshrapnel. Structuralandmaterialpropertiesthatarethoughttobeofimportancewhen consideringblastresistantmaterialsincludelightness(density),ductilityand high impact resistance. Oil Palm shells (OPS), an industrial waste material thatareabundantlyavailableinMalaysia,havebeenshowntopossessthese properties. Fibres added into concrete have also been shown to increase thetoughnessandimpactresistanceoftheconcrete.Hencethisresearchis targetedatdevelopingaconcreteincorporatingOPSandfibrestobereferred toasOilpalmShellFibreReinforcedConcrete(OPSFRC)tobeusedinblast resistantstructures. Research collaboration with overseas experts on impact, dynamic and blasttestsissignificanttowardsthesuccessfuldevelopmentoftheselocal materials into potential structural material. Modelling of OPSFRC using appropriatesoftwareisalsovitaltosuccessfullydevelopingitintoapotential blastresistantmaterial.Theseobjectivescanbesummarisedasfollows: Objectives To design a mix proportion for OPSFRC Toinvestigatefreshandhardened concretepropertiesofOPSFRC To explore the microstructure of OPSFRC To investigate the structural properties of materials that are relatedtoblastloadings To probe the impact, dynamic and blast resistant behaviours of structuralelements To model these structures using numerical methods to withstand blastloadings Methodology After selecting appropriate fibres, mixturedesignforOPSFRCwillbe designed.UsingX-RayDiffraction (XRD)andfieldemissionscanning electronmicroscope(FESEM),the micro-structural characteristics of OPSFRC will be investigated. Further, investigations on the mechanical and structural behaviour of OPSFRC will be carried out. Finally, the impact, dynamic and blast resistant properties of OPSFRC will be HIR Annual report 2011.indb 69 carried out using the expertise from the Universities of Liverpool and Sheffield in the UK and Melbourne University in Australia. Local collaboration with National DefenceUniversityofMalaysiahas been established and subsequent live tests are planned to be done at their facility. Finally, structural engineering software will be used in the modelling and comparison oftheexperimentresults Possible High Impact Journals forPublications Outcomes Collaborators Emergence of environmentally sustainableconcrete Prof. Dr. S. G. Millard, Xi’an Jiaotong-Liverpool University, Jiangsu,China Development of OPSFRC with energy absorbing characteristics towithstandblast Understanding the dynamic, seismic and blast resistant propertiesofOPSFRC Modelling of blast concreteandstructures resistant Construction Materials and Building CompositesA&B MaterialsandDesign Building&Environment EnergyandBuildings Engineeringstructures Dr. Andrew Tyas, University of Sheffield Dr.GrahamSchleyer,Universityof Liverpool Prof. Dr. P. Mendis, University of Melbourne,Australia Prof. Dr. Faisal, National Defence UniversityofMalaysia Lt.Kol.ProfMadyaIr.DrNorazman Bin Mohamad Nor, National DefenceUniversityofMalaysia 24/05/2012 9:44:53 70 High Impact Research Annual Report 2011 Project No: UM.C/625/1/HIR/MOHE/ENG/03 Title: Chemically and Electrochemically Generated Superoxide Ion in Deep Eutectic Solvents and Ionic Liquids and their Applications Principal Investigator : Professor Dr. Mohd Ali Hashim Faculty : Department of Chemical Engineering, Faculty of Engineering SummaryofResearchProposal This research program is on the synthesis and applications of ionic liquids (ILs) and deep eutectic solvents (i.e. low cost ionic liquids) or DES for the processing of biofuel, extraction of industrial products and generation of superoxide ion in ILs and its use in the destruction of hazardous materials suchaschlorinatedhydrocarbons. Theprogramcanbeclassifiedintothreeprojects: 1. Generation of superoxide ions in ionic liquids and its use in the destructionofhazardousmaterialssuchaschlorinatedhydrocarbons. 2. Development of upstream and downstream processes in biodiesel productionfromvariouscategoriesofpalmoilderivedfromthemilling operation. The upstream process is the pretreatment of high free fatty acid oils and the downstream process comprises the purification of biodieselusingDES. 3. Synthesis of DES and investigations of these solvents for different industrialapplications,suchasfortheextractionofsodiummetaland extractionofaromaticcompoundsfromaliphatic-aromaticmixture. Objectives SynthesisandcharacterizationofnewtypesofDESandILs Developmentofgreenprocessesinthefieldofbiofuel Extractionofindustrialmaterialsanddestructionofhazardousmaterials Investigationoftheoptimumconditionsinthesynthesisandapplicationsof DESandILs Methodology The chemical generation of O2●- in ILs is carried out by dissolving KO2 in the corresponding IL, while electrochemical generation is carried out by reductionofO2toO2●-inILsfollowedbyanalysisusingcyclicvoltammetryand chronoamperommetry techniques. The long term stability of the generated O2●-isachievedbytheapplicationofKO2inaproticsolvent,dimethylsulfoxide inthepresenceofthecorrespondingIL.UV-visiblespectrophotometeryatan absorbancerangeof190–400nmisusedtodeterminethestabilityofO2●-. ThechemicallygeneratedO2●- isthenusedforthedestructionofhazardous materials DES are synthesized and characterized using various equipment, and then hydrocarbonmixturesatdifferentconcentrationsarepreparedforliquid-liquid extractionexperiments.Samplesareanalyzedbygaschromatography SodiumisdissolvedinDESandthesolubilityequilibriumatagiventemperature is determined via shake flask method. The conductivity is determined by gravimetricmethodandthestabilitybycyclicvoltammetry BiodieselistreatedwithDESforbothupstreamanddownstreamoperations. The FFA content is determined by following the American Oil Chemist’s Societymethod(Ca5a-40),CommercialFatsandOils(AOCS,1997).Samples arewithdrawnfromtheupperlayerandtestedusingliquidchromatography andgaschromatography HIR Annual report 2011.indb 70 24/05/2012 9:44:53 High Impact Research Annual Report 2011 Outcome New knowledge in Chemical Engineering and Environmental Engineering Possible High Impact Journals forPublications EnvironmentalScience&Energy BioresourceTechnology Novel products for industrial applications ElectrochemicaActa Development of chemical processesutilizingDESandILs SeparationandPurification Optimum conditions for the followingprocesses:pre-treatment of low grade oil, purification of biodiesel, extraction of sodium metal, superoxide generation and its stability in ILs and destruction ofhazardousmaterials FuelProcessingTechnology Technology Energy&Fuel 71 Collaborators Assoc. Prof. Inas M. AlNashef, Dept.ofChemicalEng.,KingSaud University,SaudiArabia Assoc. Prof. Norbani Binti Abdullah, Dept. of Chemistry, UniversityofMalaya Assoc. Prof. Farouq S. Mjalli, Petroleum&ChemicalEng.Dept., SultanQaboosUniv.,Oman FluidPhaseEquilibria Benchmarking the newly selected solventswithconventionalones Project No: UM.C/625/1/HIR/MOHE/ENG/04 Title: Impact of Solar Energy Penetration on National Power Grid and its Solution Principal Investigator : Dr. Hazlie Mokhlis Faculty : Department of Electrical Engineering, Faculty of Engineering SummaryofResearchProposal InMalaysia,oneofthemostpromisingsourceofrenewableenergythatcan beutilizedissolarenergy.Atpresent,Photovoltaic(PV)systemhasbegunto beusedinMalaysiamainlyfordomesticusagesuchastoheatwater.With thecurrenttrendofenvironmentalawarenessandincreaseoffuelcosts,in thenearfuture,PVwillbeusedtogenerateelectricityonalargescaleand injectedintothepowergridsystem. The integration of a large number of solar panels will have far reaching consequencesnotonlyonthedistributionnetworksbutalsoonthenational transmissiongrid.TheincreasingconnectionofPVinthedistributionsystem could cause various problems that can be categorised in three aspects; power quality, protection and network performances. Such problem might leadtoundesirableeventssuchassystemdisturbancesandblackout. Objectives This research will be studied the impact of PVs interconnection to power system grid in the three mentionedaspects:1. Protection The possible solutions to address the impacts of PVs interconnection to the protectionaspectofapower systemgridwillbestudied 2. NetworkPerformance An effective monitoring technique for the network and the impacts of PVs interconnection on the network performance will be obtained HIR Annual report 2011.indb 71 Methodology 3. PowerQuality The power quality of a power system grid and possible solutions to address the impacts of PVs interconnection to power qualitywillbedetermined The steady-state and dynamic PV generator models (including PV,MPPT,andInverter)forpower systemanalysiswillbeaddressed asamainobjective The background of power system networks and the issues of PVs interconnection will be reviewed. A networks data such as IEEE distribution test systems, IEEE transmissiontestsystemsandalso utilitydatamainlyfromTNBwillbe collectedandusedinthisresearch. Based on the literature reviewed anddataacquisition,steady-state and dynamic modelling for PV arrays, MPPT and Inverters will be obtained. Simulation studies will be implemented in PSCAD/ 24/05/2012 9:44:53 72 High Impact Research Annual Report 2011 EMTDC software in order to find theimpactofPVsinterconnection topowersystemgrid Outcome Understanding on the impact of PVs interconnection in term of Protection, Power Quality, and networkperformance PossiblesolutionstoaddressPVs impactstogridsystem Possible High Impact Journals forPublications Renewable & Sustainable Energy Reviews IEEE Transactions on Power Systems Collaborators Dr Abdul Rahman Khalid (Tenaga NasionalBerhad) Prof. Dr. Terzija (University of Manchester) Electrical Power and Energy Systems AppliedEnergy New Dynamic and steady state modelsforPVsarrays,MPPT,and inverter Project No: UM.C/625/1/HIR/MOHE/ENG/05 Title: Design and Construction of Early Detection of Dengue Diagnostic Device Principal Investigator : Associate Professor Dr. Fatimah Ibrahim Faculty : Department of Biomedical Engineering, Faculty of Engineering SummaryofResearchProposal Dengue infection has been estimated by World Health Organization (WHO) toaffect50millionpeopleworldwide,resultinginmorethan20,000deaths annually. This is an increasing threat to over 2.5 billion people living in the tropicsandthesub-tropics.However,thecurrentdenguediagnosticmethods aretedious,needhigh-levelexpertiseandconsumeconsiderableamountsof expensivechemicalsinsophisticatedlaboratorieswithexpensiveequipment thatisnotavailableinmanyhospitals.Inaddition,theavailableequipmentis oftennotintegratedwithintelligentcomputerizedsystems. With these limitations identified, there is an obvious and urgent need to developanalternativeportableapproachthatisinexpensive,fastandeasyto useatthePoint-Of-Care(POC). Objectives Methodology The objective of the proposed workistodevelopaninexpensive, integrated, easy-to-use, and portable platform based on microfluidicsfortherapiddiagnosis of Dengue at the POC. This POC device will involve innovations in critical components including micro-fluidics, packaging, reagent handling and storage, and waste handling. The device will be based on the field of centrifugal microfluidics. As a whole, microfluidics aims to miniaturize laboratory processes to create portable diagnostic devices, bringingthediagnosticpowerofa completelaboratorytothePOC The overall methodology for the project will be divided into the following: HIR Annual report 2011.indb 72 • Separateserumfromwhole blood. The Dengue virus resides in the serum of infected individuals and must be separated and purified from the whole blood • Perform an automated ELISAtocaptureaDengueuniquebiomarker:theNS-1 glycoproteinfromserum The following experimentation is envisionedforthisproject. • The microfluidic CD is designedandfabricated • Experimental procedures using control and infected samplesforcharacterization purposes • Statistical analysis to confirm the efficiency and efficacy of the device, and thereliabilityoftheresults 24/05/2012 9:44:53 High Impact Research Annual Report 2011 Outcome Theoutcomeofthisprojectwillbe a novel device, capable of rapidly diagnosing dengue patients at thePOC,whichwillresultinearly treatment and better patient outcomes. Although this project focuses on NS1 detection, the success of developing a portable miniaturized ELISA POC CD will establish the foundations for adapting the device to detect other Dengue biomarkers (IgM, IgG) as well as other infectious diseases,suchasMalaria,HIVand Leptospirosis Possible High Impact Journals forPublications Critical Reviews in LaboratorySciences Clinical BiosensorsandBioelectronics SensorsandactuatorsB-chemical BiomedicalMicrodevices ExpertSystemswithApplications 73 Collaborators University of Malaya Medical Centre CentreforBiomedicalEngineering, University of Surrey (Prof. M.P. Hughes, Dr. F. Labeed, Dr. H.O. Fatoyinbo) Prof. Marc Madou, Biomedical, Mechanical and Aerospace Engineering Department, Faculty ofEngineering,UCIrvine Prof. Michel G. Bergeron, Department of Medical Biology, LavalUniversity Project No: UM.C/625/1/HIR/MOHE/ENG/06 Title: Experimental Investigation of New Bioenergy Sources for Biofuel from Tropical Biodiversity Principal Investigator : Professor Dr. T.M. Indra Mahlia Faculty : Department of Mechanical Engineering, Faculty of Engineering SummaryofResearchProposal The fast depletion of fossil fuels, coupled with the increasing awareness of environmentalissues,concernforincreasinggreenhousegasemissionsand escalating petroleum prices, have led to concerted efforts in thesearchfor renewableandenvironmentallyfriendlyalternativeenergysources.Bioenergy isrenewableenergyderivedfrombiologicalsources.Bioenergytechnologies userenewablebiomassresourcestobeusedforheat,electricity,orvehicle fuel. A variety of fuels can be made from biomass resources, including the liquidfuelsethanol,methanol,biodiesel,Fischer-Tropschdiesel,andgaseous fuelssuchashydrogenandmethane.Anewagriculturaltrendistheuseof plantbiomasstoprovideliquidfuelscalledbiofuels.Biofuelsarebecomingan increasinglyimportantalternativesourceofenergy Biofuelcurrentlyfallsintotwocategories:ethanol,whichiscompatiblewith gasolineengines,andbiodiesel,whichiscompatiblewithpetroleum-based diesel engines. Ethanol is an alcohol product produced from two basic feedstocks:starch-basedfeedstocks,suchascorn,grain,wheat,barleyand grainsorghum;andsugar-basedfeedstocks,suchassugarcane,sugarbeets, fruits,citrusmolassesandcane(sweet)sorghum.Itcanbeusedasafuel, mainlyasabiofuelalternativetogasoline.Whencombinedwithgasoline,it increasesoctanelevelswhilealsopromotingmorecompletefuelburningthat reducesharmfulemissions.However,oilseedfeedstockssuchaspalm,soy andrapeseedareusedforbiodieselfuel Malaysian Government has now created The National Biofuel Policy (NBP) where Malaysia has the potential to lead the way in biofuels production capitalizingonitsvastproductionofagriculturalproductsandby-products. Hence,theNBPisadriveforextensivedevelopmentofthebiofuelssector to ensure their greater use in the country. The NBP encourages the use of biofuelsinlinewiththenation’sFive-FuelDiversificationPolicy.TheNational BiofuelPolicysetstheplatformforattainmentofthefollowingobjectives:a. supplementingthedepletingsupplyoffossilfuelswithrenewableresources; b. mobilizing local resources for biofuels; c. exploiting local technology to generate energy for the transportation and industrial sectors; d. paving the way for exports of biofuels; and e. benefiting from the spin-off effect of more stable prices for palm oil. This project will explores the potential new bioenergy sources from Malaysia’s biodiversity as well as the method and impactofbiofuelmassproductionsystemsonbiodiversity HIR Annual report 2011.indb 73 24/05/2012 9:44:53 74 High Impact Research Annual Report 2011 Objectives Methodology Infrastructuralcontributions Tofindpotentialbioenergysources fromMalaysia’sbiodiversity Literaturereview: New bioenergy lab equipmentsandfacilities To investigate the calorific value fromselectednewenergysources fromMalaysia’sbiodiversity To propose the method of processingoftheselectedbiofuel formassproduction Toinvestigatethepotentialadditive for the biofuel to enhance quality ofthefuel 1st stage : Raw material and feedstockpreparation • Soxhletextractor 2nd stage procedures • Rheometer : Experimental 3rd stage : Statistical analytical andfurtherimprovement 4thstage:Developanddesignthe methodofprocessingthepossible biofuelformassproduction Outcome with • Calorimeters • Kinematicviscometer Possible High Impact Journals forPublications Renewable & Sustainable Energy Reviews(If2009=4.842) Biomass&Bioenergy(3.326) Outputsexpected Energy(2.952) The study serves as primary researchtoexploitnewbioenergy sources from Malaysia’s biodiversity and the potential feedstock such as durian, pumpkin,mangosteenseedetc AtmosphericEnvironment(3.139) Showthecalorificvalue,kinematic viscosityandphysicochemicalfuel propertiesofnewexploitedbiofuel Explore the relationship between calorific value and bioenergy propertiesforbiofuel Proposethemethodandimpactof biofuel mass production systems onbiodiversity. Perform the potential additive for the biofuel to enhance quality of thefuelenergy Fuel(3.179) AppliedEnergy(2.209) Collaborators Hamdani Umar, Syiah Kuala University,Acheh,Indonesia Irwansyah Idram, Syiah Kuala University,Acheh,Indonesia Prof Dr Ayhan Demirbas, Sirnak Universitesi Rektorlugu, Turkey DrAdiSurjosatyo,DepokCampus, Indonesia Project No: UM.C/625/1/HIR/MOHE/ENG/07 Title: Clean Diesel Technology for Military and Civilian Transport Vehicles Principal Investigator : Professor Dr. Masjuki Hj Hassan Faculty : Department of Mechanical Engineering, Faculty of Engineering SummaryofResearchProposal Thedieselengineisbecomingverypopularforhighertorque,reliability,less maintenance requirement and easy adaptability with alternative liquid fuels andheavy-dutyservice. This project focuses on a most critical aspect of today’s world: energy, environmentandsustainablegrowth. Target: 1. OptimizingperformanceofBiofuel. 2. Reductionofhazardousengineemissions Ideally, a fuel (e.g. diesel fuel C14.5H 31) should produce only CO2 & H2O as exhaustemissionswhenitiscompletelyburnedinsidetheenginecylinder. HIR Annual report 2011.indb 74 24/05/2012 9:44:53 High Impact Research Annual Report 2011 75 Itisimpossibletoachievezeropollutantgasesfromcylindercombustionof any hydrocarbon fuels (CnH2n+2). But the combustion must be controlled to achieve maximum thermal efficiency with lowest exhaust emissions and in ordertoachievethisoptimumlevel,modificationshouldbedoneonboththe fuelandenginesystem. Objectives Methodology Study on emission characteristics of PAH, NOx, unburned HC and PMforfueladditiveandbioethanol blended diesel in an unmodified automotivediesel Physiochemical properties improvementbyusinganti-oxidant additivesandbiofuel To optimize the trade-off between NOx and soot formation while using EGR in a direct injection dieselengine To compare the effect of injection pressure on emission characteristics by using electronicallycontrolledrotaryfuel injectionpumpandacommon-rail injectionsystem Compare the properties of Jatropha biodiesel and Diesterol (ternary)blendswithDieselfuel. Studyontribologicalcharacteristics andcarbondepositonautomotive components and lubricating oil, degradation when operated with bioethanolblendeddiesel Possible High Impact Journals for Publications: 71ISItier-1paper Tribologicaltestingofmodifiedfuel andlubeoil Collaborators Exhaust Gas Recirculation (EGR) technique Prof.Dr.MasahiroShioji Diesel Particulate Strategy Filter(DPF) Department of Energy Conversion Science GraduateSchoolofEnergy IdlingReductionstrategy Combustion & Power Engineering Lab Outcome KyotoUniversity,Japan This project will develop a state of the art research facilities for automotive research in University ofMalaya PublicationinhighimpactJournals Human resource development for R&D Patents: Automotivesectormoved up to the 2nd position in 2010 from 4th in 2009 based on overall volumeofpatentactivityThomson Reuters Derwent World Patents Index (DWPI). So there is a huge potential for generating patents fromthisproject Project No: UM.C/625/1/HIR/MOHE/ENG/08 Title: Multiaxial Fatigue of Elastomeric Materials in Biofuel System Principal Investigator : Dr. Andri Andriyana Faculty : Department of Mechanical Engineering, Faculty of Engineering SummaryofResearchProposal Thepresentprojectcanbeconsideredasanattempttowardanintegrated durability analysis of industrial elastomeric components subjected simultaneously to fluctuating multiaxial mechanical loading and hostile environments. Indeed, in addition to fluctuating multiaxial mechanical loading,manyengineeringcomponentsareexposedtohostileenvironments suchasbiofuelsystems.Inthiscase,thedurabilityinserviceofelastomeric componentsisstronglyaffectedbytheinteractionexistedbetweenmechanical loadinganddiffusionofliquidintothematerial.Thus,theunderstandingofthe aboveinteractionbecomescrucial. HIR Annual report 2011.indb 75 24/05/2012 9:44:53 76 High Impact Research Annual Report 2011 Objectives Methodology Outcome To investigate the interaction between multiaxial stress states and diffusion of liquid biofuel into elastomers undergoing multiaxial largedeformations This research will be conducted according to the two following majorworks: New finding on the effect of multiaxial stress state on the diffusion of liquid biofuel into elastomers 1. To develop a continuum mechanicalmodeltodescribethe aboveinteraction To study the fatigue behavior of elastomers under multiaxial loading in the presence of liquid biofuel 2. Experimental works. Various mechanical testing will be conducted in order to investigate the interaction between multiaxial stress state and diffusion of liquid biofuel. At the same time, multiaxial fatigue testing of elastomers in the presence of hostile liquid biofuel will be performed. Microstructural analyses of materials are also to be conducted. Subsequently, theexperimentaldatawillbe analyzed Theoretical works. Development of a continuum model to describe the phenomena observed in experiments. The model will be developed under the framework of thermodynamics of irreversible processes and validated by the obtained experimental data. After validation, the model will be implementedintocommercial finite element code in order to simulate real engineering elastomericcomponents New theory on the modeling of couplingbetweenmultiaxialstress stateanddiffusionofliquidbiofuel inelastomers New finding on the multiaxial fatigue of elastomers in the presenceofhostileliquidbiofuel Possible High Impact Journals forPublications Journal of the Mechanics and PhysicsofSolids MechanicsofMaterials PolymerTesting InternationalJournalofFatigue InternationalJournalofSolidsand Structures Collaborators Prof.ErwanVerron.EcoleCentrale deNantes,France Dr. Nicolas Saintier. Ecole Nationale Supérieure d’Arts et Métiers,Bordeaux,France Dr. Sylvie Castagnet. Ecole Nationale Supérieure de Mécanique et d’Aérotechnique, France Project No: UM.C/625/1/HIR/MOHE/ENG/09 Title: 2Micron Fiber Laser and Nanowires Principal Investigator : Professor Dr. Sulaiman Wadi Harun Faculty : Department of Electrical Engineering, Faculty of Engineering SummaryofResearchProposal Recently with the competition of high power fiber laser development, more and more people realized the importance of the laser efficiency. Thulium hasshownitsunsurpassedadvantageintermsoflaserefficiencyduetothe uniquecrossrelaxationenergytransferprocess.Accordingtothetheoryof crossrelaxationenergytransfer,theincreaseofthuliumdopingconcentration isanaturalsteptofurtherimprovethelaserefficiency.NewtypesofThulium– dopedfiber(TDF)andpumpingschemesaswellasnovelarchitecturesneed tobestudiedandexploredtoimprovethelaserefficiency.Thisworkinvolves spectroscopicstudiesonvarioustypesofTDFsandTDFlasersdemonstration usingvarioustypesofgainmediumandpumplaserstoexplorethepossibility togenerateahighlyefficientandsinglefrequencylasersat1.9-micronregion. HIR Annual report 2011.indb 76 24/05/2012 9:44:53 High Impact Research Annual Report 2011 77 The second project focuses on designing, modeling, fabricating and packaging optical fiber micro/nanowires and to develop novel structure such as Mach Zehnder interefometer, knot resonators etc. Nanowires, also referred to as photonic wires, microfibers, nanofibers or nanotapers, are fiber waveguides with sub-wavelength core diameters (typically < 1μm). Such a small core diameters offer access to extreme fiber properties such asstrongconfinement,largeevanescentfields,greatconfigurabilityandlow loss connection. New applications of these devices will also be explored suchasfibersensorandfilters.Theresonatorsareusefulin2micronlaser experimentsandsupercontinuumgeneration. Objectives Methodology The first project aims to develop anefficientfiberlaseroperatingat 2-micron wavelength region using various types of gain medium such as Thulium-doped fiber and ThuliumYtterbiumco-dopedfiber. Theobjectiveofthesecondproject is to design, model, fabricate and package optical fiber micro/ nanowires as well as to explore new applications for this device suchasloopresonatorandsensor New gain medium for 2 micron fiber lasers will be developed in collaboration with Central Glass and Ceramic Research Institute, India. Both cladding and core pumping techniques will be used for lasing experiments. Some works on mode-locked fiber laser will also be explored. Micro/ nanowireswillbefabricatedusing aflamebrushingtechniques.Other techniques such as laser heating and fiber heater will also be used torealizeanano-scaledevice Outcome New knowledge and devices are expectedfrombothprojects Possible High Impact Journals forPublications OpticsLetters IEEEPhotonicsJournal LaserPhysicsLetters SensorandActuatorA IEEESensors Collaborators HarithAhmad,PhotonicsResearch Center,UniversityofMalaya Mukul C. Paul, Central Glass and CeramicResearchInstitute,India B.M.AzizurRahmanandKenneth T. V. Grattan, City University London Moh. Yasin, Airlangga University, Indonesia Noriah Bidin, Universiti Teknologi Malaysia HIR Annual report 2011.indb 77 24/05/2012 9:44:53 78 High Impact Research Annual Report 2011 Project No: UM.C/625/1/HIR/MOHE/ENG/10 Title: Biomechanical System for Hard and Soft Tissues of Normal ad Disabled Subjects Principal Investigator : Associate Professor Dr. Noor Azuan Abu Osman Faculty : Department of Biomedical Engineering, Faculty of Engineering SummaryofResearchProposal Tissuesofthehumanbodyplayabigroleindecidingthestateofhealthofthe individuals.Thisstudywilllookatvariouscomponentsofthebodytissues and factors affecting their physical states and physiological performances. Specifically,thestudywillinvolveinvestigationsrelatingtotheeffectofvessel stiffnessonmodulationofbioavailabilityofnitricoxide,especiallyintermsof characterizinggeneexpressioninculturedendothelialcells. Tissue injury is another area of concern to both researchers and practicing scientists.Thisstudywilllookintothedevelopmentofanovelcarbumper energy damping system in newly developed cars to improve bumperpedestrianimpactperformance.Hardtissueimplantswillalsobestudiedby looking specifically on dental implants from functionally graded materials. Mathematical studies on tissues will involve knee joint biomechanics in associationwithosteoarthritisaswellasmathematicalmodelingofartificial heartvalve. At the practical application level, one study will focus on investigating the interface pressure between the stump and socket in trans-tibial prosthesis usingSeal-inlinerandDermo-liner.Inadditiontothat,theabilitytobalance among trans-tibial amputees by using Biodex Balance System will also be lookedat.ApplicationofmodernCAEpackagestodevelopa3Dmodelofthe hipimplantusingafunctionalgradedmaterialandthedesignoffunctionally gradedhipstemprosthesisareanothertwoareasthatwillbestudied.Thelast areathatwillbeworkedonwithinthisresearchtopicisthecharacterization ofprosthesisandorthosisusers’gait,targetinginparticularatunderstanding theoverallworkingofasmartprostheticleg. Possible High Impact Journals forPublications ArtificialOrgans Journal of the Mechanical BehaviourofBiomadicalMaterials Biomicrofluidics Computer methods in Applied mechanicsandEngineering Hypertension Journal of Biomedical Materials Research(PartA) Annual Review of Biomedical Engineering Journal BiomechanicsElectrophoresis JournalofDentalResearch HumanMovementScience ComputationalMechanics Cardiovascularresearch ClinicalBiomechanics ActaBiomaterialia of JournalofWear Biomaterials Circulation Collaborators Prof.Dr.WalterHerzog,University ofCalgary,Canada Prof.Dr.AlbertoAvolio,University ofMarquarie,Australia CenterofBiomedicalEngineering, UniversityofSurrey,UK Dr.MehdiJonoobi,LuleaUniversity ofTechnology,Sweden DentalMaterials HIR Annual report 2011.indb 78 24/05/2012 9:44:54 High Impact Research Annual Report 2011 79 Project No: UM.C/625/1/HIR/MOHE/ENG/11 Title: Biodiesel from Pyrolytic Oil Produced from Palm Shell by Hydrodeoxygenation Process Principal Investigator : Professor Dr. Wan Mohd. Ashri Wan Daud Faculty : Department of Chemical Engineering, Faculty of Engineering SummaryofResearchProposal OneoftheseriousproblemsinMalaysiaisthedisposalofpalmshellwaste generated from oil palm industries. One of the methods to overcome this situationisbyusingitasanalternativefuel.Theconversionofthiswasteto pyrolyticoilbypyrolysisprocessisattractivesincetheproductthatcanbe utilized as chemicals or biodiesel fuel. Besides, the process also produces activatedcarbonandvaluablegasasbyproducts.Forbiodieselpurpose,the oilneedstobeupgradedinordertoincreaseitsfuelproperties.Theproperties areinfluencedbysubstantialamountsofsulfur(S),nitrogen(N)andoxygen (O)heteroatoms.Themostabundantheteroatominthepyrolyticoilderived frombiomassisoxygenandlimitedcontentsofsulphurandnitrogen.Thus hydrodeoxygenationisoneofthemajorreactionsoccurredduringupgrading process.Hydrodeoxygenationhasbeenconsideredbymanyresearchersas most suitable process to remove oxygen contents in the oil. In the present study, pyrolytic oil produced from palm shell is chosen as model oil for hydrodeoxygenation. The oil classified as low-grade pyrolytic oil with high oxygenandwatercontents(71.40wt%and53wt%),soarechallengingto becompletelydeoxygenated. The main purpose of this work is to shed some light on the role of the catalystsulphidationinhydrodeoxygenation.Theworkwillbeperformedby using several conventional catalysts such as CoMoS/Al2O3; 5% Pd/Al2O3; MoS2; CoMoS; NiMo/ Al2O3; Pt/TiO2; Pt/Al2O3 Pt/SiO2 and ZSM-5 Zeolite. The study will continue with several investigations on process parameters and characterization of yields product. The project will also cover further development of renewable energy of biomass based that that is more environmentalfriendly.Moreover,Malaysiaisrichinagriculturewasteashas may types of raw materials that can be utilized for such process. Hence, exploringnewapplicationofbiomasswastetobiodieselisanimportantstep indevelopingenergyfrombiomass. Objectives Methodology Study on effects of the catalyst prepared 1. Materials 2. KineticTest Theworkwillbeperformedbyusing several conventional catalysts such as CoMoS/Al2O3; 5% Pd/ Al2O3;MoS2;CoMoS;NiMo/Al2O3; Pt/TiO2;Pt/Al2O3Pt/SiO2andZSM5 Zeolite. The chemicals used in the synthesis of the catalysts are Ni(NO3)2·6H2O (Alfa Aesar, 99%), Fe(NO3)3·9H2O(AlfaAesar,99%), (NH4)6Mo7O24·4H2O(Alfa Aesar, 99%),Co(NO3)2·6H2O(AlfaAesar, 99%), (NH4)6W12O39·xH2O (Aldrich, 99%), (NH4)2HPO4 (Aldrich,99%) Catalytictestswillbecarriedoutin aliquidphaseina500mlautoclave (high pressure high temperature) with a magnetic stirrer. The autoclave filled with the reaction mixture consisting of pyrolytic oil (differentamountoffeeds),solvent (different solvent) and catalyst (different type of catalysts). After that the autoclave will be heated toarequiredreactiontemperature and pressurized with gas. Subsequently, the stirring started. Thereactiontimewillbemeasured fromthestartofthestirring Studyonfeedcompositions Studyoneffectsofsolventtypes Study on process parameter effectsonproduction(temperature, pressureandreactiontime) Optimization of the process variable by Response Surface Method(RSM) Characterization of physical and chemicalcompoundsofHDOoil Characterizationstudyoncatalysts beforeandafterHDO StudyonstoragestabilityofHDO oil To estimate process production cost of HDO oil (Economic engineeringstudy) Development of HDO process design HIR Annual report 2011.indb 79 The chemicals used for the reactivity tests are guaiacol (Alfa Aesar, 98%). The gases employed areH2(Airco,Grade5,99.99%),He (Airco,Grade5,99.99%),CO(Linde Research Grade, 99.97%), 0.5% O2/He(Airco,UHPGrade,99.99%), O2(Airco,UHPGrade,99.99%),N2 (Airco,Grade5,99.99%) 3. AnalyticalMethods a) Scanning Electron Microscopy(SEM) The SEM images of the samples will be obtained by dispersing the powders on double-faced 24/05/2012 9:44:54 80 High Impact Research Annual Report 2011 conducting tape fixed on a brass support. The sample will be coated with graphite using the sputtering technique on an LVC 76apparatus,PlasmaScienceInc. The microscope used is a JEOL JSMT-300 b) Fourier Transform Infrared Spectroscopy(FT-IR) The Fourier transform infra-red (FT-IR) spectroscopy will be used to classify the chemical types in the HDO oil and also to identified thecatalystsafterandbeforeused in HDO process. The analysis will be conducted by using FT– IR spectrometer (Perkin Elmer, Spectrum 400). The oil samples pressed into a disc with small amountofKBr.Thesampleswillbe scannedintherangeof550–4000 cm-1witharesolutionof4cm-1 c) GC-MSAnalysis The chemical compositions determined by gas c h r o m a t o g r a p h y / m a s s spectroscopy (GC/MS). The analysis will be performed with Agilent HP 7890A gas chromatograph equipped with an Agilent HP 5975C mass-selective detector (mass spectrometer). Highpurityheliumwillbeusedas carriergasatconstantflowrateof 1.0 ml/min. The Agilent DB-Petro 50 m column will be used in the GC/MS, with an inner diameter of0.2mmandafilmthicknessof 0.5μm.Theanalysisisstartedby heating the column at 40 °C and kept isothermal for 10 min. Then the temperature will be increased to75°Cwitharateof0.90°C/min. When the temperature reaches to 75°C,asteeperrampof1.10°C/ min will be applied until 120 °C. Finally, the temperature will be raisedto200°Cwithaverysteep rampof10°C/minfor20min.The inletpressureofthecolumnwillbe set at 135 kPa and the scanning rangeis10–300amu d) ThermogravimetricAnalysis Thermogravimetric analysis of the raw pyrolytic oil and HDO oil will be performed using a thermogravimetric analyzer (TGA 4000, Perkin Elmer). The analysis will be done under nitrogen flow rateof25ml/minandheatingrate of40°C/min e) Elementalanalysis The elemental analysis of the oils will be determined with the Model 2400 Perkin- Elmer Series II CHNS/O Analyzer. Each of elemental values will be used for calculating the molar ratios of H/C and O/C in the HDO oils by followingequation: (1) (2) These values are also used for calculating the high heating value (HHV). In this study, HHV will be calculated by the following equation (3) that proposed by Dulong HHV (MJ/kg) = 0.3383 C + 1.443 (H - (O 8)) + 0.0942 S (3) f) Viscosity Theviscosityofthesampleswillbe measured using a cone and plate rheo-meter(Viscotester,Haake).A temperature ramp (20–140 °C) will be applied to obtain the viscosity as a function of the temperature. Theshearratewillbesetatafixed valueof30s-1 Outcome Novel theories/New Knowledge findings/ Usingofseveraltypesofprepared catalystsforhydrodeoxygenationof palmshellpyrolyticoilisnewstudy thatastheauthor’sknowledgeno workwasdoneaboutitpreviously. This hydrodeoxygenation could considerably reduce the final cost of biodiesel production. The noveltywillbeoncatalystprepared andprocessoperation SpecificorPotentialApplications. The HDO oil has a great potential tobeusedasbiodiesel Possible High Impact Journals forPublications BiomassandBioenergy BioresourceTechnology JournalofAppliedCatalysis AppliedEnergy Fuel FuelProcessingTechnology HIR Annual report 2011.indb 80 24/05/2012 9:44:54 High Impact Research Annual Report 2011 81 Collaborators Prof. Dr. Farid Nasir Bin Ani, Universiti Teknologi Malaysia, Malaysia Prof. B.C. Meikap, Indian Institute ofTechnology,India Prof. A.V. Patwardhan, Institute of ChemicalTechnology(ICT),India Project No: UM.C/625/1/HIR/MOHE/ENG/12 Title: Synthesis and Development of Novel Nanocomposite Silver for Metamaterials at Optical and Microwave Frequencies Principal Investigator : Associate Professor Dr. Mohd Rafie Johan Faculty : Department of Mechanical Engineering, Faculty of Engineering SummaryofResearchProposal Recently,artificiallyconstructedmetamaterialshavebecomeofconsiderable interest,becausethesematerialscanexhibitelectromagneticcharacteristics unlikethoseofanyconventionalmaterials(Smithetal.,2004;Pendryetal, 2006).Artificialmagnetismandnegativerefractiveindexaretwospecifictypes ofbehaviorthathavebeendemonstratedoverthepastfewyears,illustrating the new physics and new applications possible when we expand our view astowhatconstitutesamaterial.Oneofthemostfundamentalphenomena in optics is refraction. When a beam of light crosses the interface between twodifferentmaterials,itspathisaltereddependingonthedifferenceinthe refractive indices of the materials. The greater the difference, the greater the refraction of the beam. For all known naturally occuring materials the refractiveindexassumesonlypositivevalues.Butdoesthishavetobethe case?In1967,Sovietphysicist,VictorVeselagohypothesizedthatamaterial withanegativerefractiveindexcouldexistwithoutviolatinganyofthelaws ofphysics(Veselago,1967).Hepredictedthatthisremarkablematerialwould exhibitawidevarietyofnewopticalphenomena,fromreversedgeometrical opticstoreversedDopplershifts.However,untilrecentlynoonehadfound such a material, and Veselago’s ideas had remained untested. In this proposal,wewillsynthesizedsilverpolymericnanocompositemetamaterials atopticalandmicrowavefrequencies.Thesampleswillbecharacterizedand testedusingseveralanalyticaltechniques.Newmodelwillbedevelopedin ordertounderstandthemechanisminvolvedandwillbecomparedwiththe experimentalresults.Usingourmodelandexperimentaldata,wewillexpect that the new materials will possess a negative refractive index behavior at opticalandmicrowavefrequencies.Wewillexpectthatanewtheorywillbe proposedbasedonthetheoreticalandexperimentalresults. Objectives To discover the new physics and establishmodelingmethod To develop new characterization techniques and to measure the physical properties of the metamaterials To design and fabricate new composite metamaterials at microwaveandopticalfrequencies HIR Annual report 2011.indb 81 To demonstrate metamaterialsbased devices for microwave and photonicapplications Methodology In this work, five parameters have been selected that could be divided into three variables parameters.Oneistheamountof the chemical components, which composed of precursor (AgNO3, g), stabilizer (Daxad 19,g), PMMA andtheotherisreactionconditions such as the reaction temperature (Temp, °C) and addition time of the reducing agent (Time, min). In this research, we used Daxad 19 and Polyethylene Glycol(PEG)for reduction of silvers salts. Then, PMMAwasaddedinthesolution. Since,PMMAactsasaprotective agent and restricts the mobility of 24/05/2012 9:44:54 82 High Impact Research Annual Report 2011 silvers ions during the reaction, agglomerationismostlycontrolled. Ag/PMMA nano-composite was characterized. Taking advantages of Daxad 19 and its miscibility with PMMA, we describe an easy synthetic route for silver nanoparticles in PMMA. Inspired from previous work on such system, we have generated composite Ag polymer nano-particles using chemical reduction method. The preparedcompositemetamaterials will be characterized by different techniques. Experimentally, the magnitude and phase of the S parameterswillbemeasured.The experimentwillbeperformedinthe microwave chamber using vector network analyzer for sweeping microwaves over a frequency range7–13GHz The sample will be placed at the focus where lens assemblies are mounted on the two microwave horns (acted as the source and detector) to produced a focused spot at a distance of 30.5 cm. For transmission experiments, a confocal setup will be used in which both the source and detector horns are placed one focal length from the sample. For the reflection experiments, the horns will be moved to the same sideofthesample.Microstructural characterization and image analysiswillbeperformedbyusing SEMandTEM.Opticalstudieswill be conducted using UV visible spectrophotometer, FTIR and Ramanspectroscopy.Modelingof metamaterials will be conducted using transfer matrix approach. The transfer matrix is used to calculatetheEMtransmissionand reflectionofmetamaterials Outcome New mechanism/theory of metamaterials at optical and microwavefrequencies Possible High Impact Journals forPublications Science Nature PhysicalReview MaterialsChemistryandPhysics AdvancedMaterials Collaborators Professor Dr Saifollah Abdullah;Faculty of Applied Sciences, UiTM, Shah Alam, Selangor Project No: UM.C/625/1/HIR/MOHE/ENG/13 Title: Sustainable Treatment of Wastewater from Latex and Rubber Process Industries by Biosorption Process Principal Investigator : Dr. Jaya Narayan Sahu Faculty : Department of Chemical Engineering, Faculty of Engineering SummaryofResearchProposal Theprimarypurposeofwastewatertreatmentsystemsistoprotecthuman and environmental health. These treatment systems employ processes that often require human and monetary resources to operate and maintain, and while some of these treatment systems are suitable for large urban communities,theymaynotbeappropriateforthesmallercommunities.For example,someofthesesystemsarecostlyandrequiredskilledworkersto operateandmaintain.Althoughengineers,scientistsandpolicymakershave attemptedtoaddresstheneedsofthesedifferentcommunitysizes,whatis oftenneglectedisthe‘appropriateness’ofthetechnology.Sometimes‘high tech’ wastewater treatment technologies that are not suitable on a longterm basis in most developing countries, may not always be the solution, andthereforeother‘appropriatetechnologies’needtobeassessedfortheir feasibilityasalternativemethods.‘Appropriatetechnology’isdefinedasthe useofmaterialsandtechnologythatareculturally,economically,andsocially suitable to the area in which they are implemented. Thus, the purpose of this project is to evaluate the feasibility and viability of biomass as filtering material/media for removal of heavy metal from wastewaters of latex and rubberprocessindustries. HIR Annual report 2011.indb 82 24/05/2012 9:44:54 High Impact Research Annual Report 2011 Objectives Methodology Outcome Because of increasing population growthandtheclearlinksbetween access to water, improved health, and economic empowerment, there is a great need for more sustainable management of water resources, and most importantly, a need to learn how sustainable treatment of water/wastewater management can be used to minimize the impact of water pollution on the future health and economic livelihoods of those living in the developing world. On site,ordecentralized,management of wastewater is defined as collection, treatment, and reuse ofwastewateratornearthepoint of generation. These systems, can provide excellent protection ofpublichealthandwaterquality, and can be integrated with water re-use The investigation of this research is divided into three phases. The firstwillbeconcernedtoSelection ofbiosobentatdifferentoperating condition, locally available biomasswastesuchaspalmshell, coconutshell,ricehusks,coirpith, saw dust, banana pith, banana stem, and orange peel will be screenedforitszincmetalremoval capacity, while the second phase is sorption test of heavy metals pollutantsinbatchprocessandthe thirdphaseisthecolumnstudyfor realindustrialwastewaterofheavy metalspollutantsandmodelling The project’s goal is to promote the development and use of environmentally beneficial technologies through obtaining independent and credible performance evaluations of commercially-ready green separation technologies in Malaysia. The results from this project will allow a reappraisal of the competing theories and practicaltechnologyofwastewater treatmentdevelopmentnotonlyin theMalayasia,butglobally Synthesis of the biosorbent: Synthesisofbiosorbentatdifferent chemical/mechanical heat treatment.i.e.microwaveradiation power, thermal activation, steam activation activation time and impregnationratioofZnCl2/H3PO4/ KOH. Different characterization of AC and raw material: palm shell i.e. physical and chemical analysis. Sorption test of heavy metals: Sorption test of heavy metals pollutants in batch reactor using new biosorbent. Column performance of new biosorbent packed bed for removal of liquid pollutants(heavymetals/dyes) Columntest:Columnperformance ofnewbiosorbentpackedbedfor removalofheavymetalspollutants (real industry waste water). Modelling and optimization for removalofheavymetalspollutants by the process of adsorption in newbiosorbentbyusingresponse surfacemethodology 83 Possible High Impact Journals forPublications JournalofHazardousMaterials BioresourceTechnology BiomassandBioenergy ChemicalEngineeringJournal Industrial&EngineeringChemistry Research Collaborators Prof.B.C.Meikap,IndianInstitute ofTechnology(IIT)Kharagpur,India Prof. Kaustubha Mohanty, Indian Institute of Technology, Guwahati, India Prof.K.K.Pant,IndianInstituteof Technology(IIT)NewDelhi,India. Prof. V.K. Srivastava, ABES IT group of institutions, New Delhi, India Prof. Prakash R. Apte, Indian Institute of Technology (IIT) Bombay,India Dr. Nivedita Sahu, Indian Institute of Chemical Technology, Hyderabad,India Prof.P.Mondal,IndianInstituteof Technology(IIT),India HIR Annual report 2011.indb 83 24/05/2012 9:44:54 84 High Impact Research Annual Report 2011 Project No: UM.C/625/1/HIR/MOHE/ENG/14 Title: Synthetic Prosthetic Socket through Stump-Liner Interfacial Stresses Measurement Principal Investigator : Associate Professor Dr. Noor Azuan Abu Osman Co-PI(s) : Prof. Dr. Ir. Wan Abu Bakar Wan Abas Faculty : Department of Biomedical Engineering, Faculty of Engineering SummaryofResearch Thestudywillfocusonthedesignanddevelopmentofatrans-tibialprosthesis usingintelligentsmartsensor,actuator,andcontroltechnique.Thefinalaim istoproduceabio-mechatronicslegwhichenhancesgeneralmovementof theamputeewearingit.Aspartofthestudy,theresearcherswilllookintothe influenceofprotectivekneebracingonthebiomechanicsofthelowerlimb joints.Abiomechanicalanalysisofthekinematicsandkineticsparameters for a foot prosthesis will also be carried out using the innovative insole technology.Animportantaspectofprosthesisstudyistheunderstandingof thepressureprofilebetweenthestumpandthesocket. Inthisresearch,aninvestigationwillbecarriedoutonthecapabilityofthe opticalfiberBragggrating(FBG)sensorstomeasuresocket/stumpinterface pressures, especially at the PT bar area, leading to the development of a novelinterfacialstressesmeasuringsystemthatcanbeappliedoversurfaces of irregular shapes. The suspension system is another issue of concern in prosthesis.Thestudywillinvolvethedesign,development,andevaluationof anewprostheticsuspensionsystem.Ontopofthat,afundamentalstudywill becarriedoutonthedifferencesbetweenSeal-inX5andDermoLinersongait andcomfortintrans-tibialamputees. Goingbacktobasics,relatedstudieswillbecarriedoutontheheart,muscles, andbrainofpatients.Asfarastheheartisconcerned,thestudywillinvolvea computationalfluiddynamicsstudyofafailingheartanda2Dcomputational fluid dynamic heart modeling. Beyond the heart, physiological studies will involvethedefinitionofthebrawn-braininteractionsystem,relatingtheeffect of stimulation of specific muscles on the health state of the brain. Effects of electromagnetic radiation on the brain activity, eye fatigue, and muscle activityofthehumanbodywillalsobelookedat. Possible High Impact Journals forPublications JournalofRehabilitation,Research andDevelopment Natureneuroscience ArchivesofPhysicalMedicineand Rehabilitation Gait&Posture American Medicine Journal of AnnalsofBiomedical;Engineering MedicalEngineeringandPhysics AppliedMathematicalModeling CardiavascularEngineering IEEEBio-medEngineering JournalofAthleticTraining JournalofBiomechanics JournalofNeuroscience Mechatronics Sport SensorsandActuatorsA:Physical JournalofBiomedicalOptics ArtificialOrgans Collaborators Asa Gudlaug Ludviksdottir, Technical Product Manager Interfaces, Össur Head Office, Iceland Prof.Dr.NigelLovell,Universityof NewSouthWales,Australia Dr. Socrates Dokos, University of NewSouthWales,Australia Dr. Mohammad Taghi Karimi, Isfahan University of Medical Sciences ClinicalBiomechanics JournalofNeurology HIR Annual report 2011.indb 84 24/05/2012 9:44:54 High Impact Research Annual Report 2011 85 Project No: UM.C/625/1/HIR/MOHE/ENG/15 Title: Automobiles Fuel Economy Standards and Label: Implementation Possibilities in Malaysia Principal Investigator : Professor Dr. T.M. Indra Mahlia Faculty : Department of Mechanical Engineering, Faculty of Engineering SummaryofResearchProposal Rapid economic growth in Malaysia is driving rapid growth in the number of automobile in the transport sector, which in turn is straining the energy supply of the country and contributing to growing negative environmental impact.Energyefficiencyimprovementforautomobilesthroughfueleconomy standards and labels can reduce the burden of this growth by establishing a minimum level of efficiency for automobiles. Today, at least five OECD countrieshavefueleconomystandardandlabelforautomobile(smallpickup trucks,sport-utilityvehicleandminivan).CanadaandKoreahavemandatory standardsforcars.Japanhasfueleconomytargetsforcars.Thetargetsare voluntarybutwidelymetduetostrongcooperationbetweengovernmentand manufacturers.SwedenandAustraliahavevoluntaryfueleconomystandard andlabelforcars.Allofthestandardandlabelarebasedonweightedaverage fuelefficiencyofnewvehiclesofacertainsizeorofacertainbrand.Inthe U.S.,theyarecalledCorporateAverageFuelEconomic(CAFE)standards. SincetheuseandnumberofautomobileshasincreasedrapidlyinMalaysia andwithincreasingfuelpriceinpreviousyears,thisisthetimetoconsider automobilefueleconomystandardandlabelsforthecountry.Fueleconomy standardandlabelisoneofthereasonswhywecannotsellournationalcar in some countries, but they can sell their inefficient cars in our country. If thethereisstillnofueleconomystandardsandlabelinMalaysiainthenear future.Thecountrywillbecomethewastebasketforinefficientvehiclefrom othercountries. Objectives Methodology To propose an appropriate fuel economy standard and labels for automobilesinMalaysia LiteratureReview To identify energy efficiency improvements potential for automobilesinMalaysia To create awareness to the potential buyer and manufacturer ofautomobileaboutthebenefitof fueleconomystandardsandlabels Todeterminethepotentialenergy, economical and environmental impact by proposing fuel economystandardsandlabelsfor automobilesinMalaysia 1st stage : The fuel economy standardsdevelopment 2ndstage:Testproceduresmethod 3rd stage : Engineering and economicanalysis 4th stage : Improvement technologies for automobile in Malaysia 5th stage : Design fuel efficiency label Outcome Outputsexpected Measurement device that fuel economy standards and label for automobiles in Malaysia will be established. Design of the current of fuel economy standard and labels for reducing fuel consumption and improvetechnologyenginetypes. Development economical and environmentalimpactbyproposing HIR Annual report 2011.indb 85 fueleconomystandardsandlabel forautomobilesinMalaysia Encouraging consumer towards better fuel economy standards vehicle will also help to reduce GHGemissions Infrastructuralcontributions Environmental automobile test equipment Trafficlightsystem Behaviorsofconsumers Protonmanufacturer VehiclestatisticaldataofMalaysia government Possible High Impact Journals forPublications Renewable & Sustainable Energy Reviews(If2009=4.842) Energy(If2009=2.952) Atmospheric Enviroment (If 2009 =3.139) EnergyPolicy(If2009=2.436) EnergyConversion&Management (If2009=1.944) 24/05/2012 9:44:54 86 High Impact Research Annual Report 2011 Collaborators Prof Dr Hadi Nur, University of Technology Malaysia (UTM), Malaysia Prof Dr Ayhan Demirbas, Sirnak Universitesi Rektorlugu, Turkey Prof Dr Susumu Tohno, Kyoto University, Japan Prof Dr Tetsuo Tezuka, Kyoto University, Japan Project No: UM.C/625/1/HIR/MOHE/ENG/16 Title: Human-Machine Interface via Brain Signals Applications Principal Investigator : Norrima Mokhtar Faculty : Department of Electrical Engineering, Faculty of Engineering SummaryofResearchProposal Inabroadcontext,HumanMachineInteraction,ormorecommonlyHuman ComputerInterface(HCI),isthestudyofinteractionbetweenahumanand a machine. It is an interdisciplinary field involving engineering, computer science and many other disciplines such as psychology, sociology and the arts. In a common human machine interface system, the input is a request or command from a human operator to the machine that is communicated via an input device such as keyboards, buttons, switches, touch screens, mice and others. The output is an appropriate response from the machine whichinformstheoperatorthattherequestorcommandhasbeenexecuted accordingly. Recent advances in the field of digital signal processing have pavedthewaytonovelandradicalchangesinthewayhumansinteractwith computers. Nowadays, it is possible to have inputs in the forms of sounds or voices produced by humans, the movements of some body parts and ElectroMyographic(EMG),Electro-Oculographic(EOG)orElectro-Encephalographic (EEG) signals. However, it is difficult to design HCIs that are functional, efficient,user-friendly,cheapandlogicalusingEMG,EOGorEEGsignalsas inputs. Today, machines including the state-of-the-art human–computer interaction systems,arestillveryfarfrombeingabletoemulatethisabilityespeciallyto servespecificmembersofsocietyliketheelderlyandthedisabledcommunity. Objectives Methodology Outcome The objective of the project is to develop human-machine interface technology via brain signals approach.TheHCIsystemswillbe modeled, simplified and applied to actuators. Although HCI is an interdisciplinary field, the whole systemintegrationwillbedesigned for real time applications. The real time applications will be the challenge to be tackled as many componentsareinvolved Thebrainsignalsitselfisverynoisy and the unit is in microvolts. The work start with input processing via brain signals identification, acquisition, filtering, feature extraction and classification. Whentheinputsignalsiscorrectly characterized and classified, the link between the input and actuator is established. Once the link is established, the systems integration is optimized for real timeresponse HCIsystems HIR Annual report 2011.indb 86 Classificationtechniquesfornoisy data Possible High Impact Journals forPublications IEEE Transactions on Biomedical Circuits and Systems (Multidisciplines) IEEE Transactions on Neural Systems and Rehabilitation 24/05/2012 9:44:54 High Impact Research Annual Report 2011 Engineering(Multidisciplines) Journal of Neural Engineering (Multidisciplines) Journal of Neuroengineering and Rehabilitation(Multidisciplines) International Journal of Innovative Computing, Information and Control(Multidisciplines) 87 Collaborators Dr. Hamzah Arof, Department of Electrical Engineering, University ofMalaya(Co-PI) Dr. Zuwairie Ibrahim, Faculty of Electrical Engineering, Universiti TeknologiMalaysia Dr.MarizanMubin,Departmentof Electrical Engineering, University ofMalaya Associate Professor Dr. Masahiro Iwahashi, Nagaoka University of Technology,Japan Project No: UM.C/625/1/HIR/MOHE/ENG/17 Title: Torque Ripple Reduction and Design Optimization of Voltage Vector Controlled PMSM Drives Supplied by Innovative Multilevel Inverters Principal Investigator : Professor Dr. Saad Mekhilef Faculty : Department of Electrical Engineering, Faculty of Engineering SummaryofResearchProposal The permanent magnet synchronous motors (PMSM) have replaced the inductionmotorsinmanyapplications.Motivatedbythehighefficiency,high powerdensity,lowinertiaanddeclinedproductioncost,thePMSMbecame the principle vehicles propulsion drive and very common in high efficiency appliances.Voltagecontrol-basedPMSMdrivessuchasdirecttorquecontrol (DTC)drivesanddirectselfcontrol(DSC)havesomeattractivefeaturesover thefield-orientedcontroldrivesmainlytheeliminationofthecurrentcontrol andaxistransformationandthesimplemotormode. The proposed project aims is to integrate the innovative hybrid multilevel inverters with the PMSM into the voltage controlled drives design. This integrationinvolves: 1. The voltage control algorithms and concepts development to accommodatetheprivilegesprovidedbythemultilevelinverters. 2. Theintroductionofamathematicaltransformationforthemotormodel that can lead to simple and direct relationship between the inverter controlswitchingsignalsandthemotortorqueandflux. 3. FurtheroptimizationandstandardizationoftheMLIdesignandswitching algorithm by modifying the inverter design to minimize the DC supply costmakingafull-utilizationoftheswitchingflexibilitythroughcarefullydesigned control algorithm and adopting the recent technologies and theindustrialstandardsintheinverterimplementation. Objectives To design a hybrid multilevel inverterwithreducedDClinkcost To adopt a modular hybrid inverter design to facilitate the implementation with standard smartpowermodules To design a modified mixed topology hybrid inverter that HIR Annual report 2011.indb 87 applies reduced number of switching devices and of simple DClinkrequirements To develop voltage control strategiesofthedesignedinverters that ensures the operation of the high power sections at the fundamental switching frequency, maintains the DC side capacitors voltage balancing and sets the dominant harmonics frequency at tolerablelevel To investigate the design of multistage hybrid inverter that suppliesthelowvoltagestagewith capacitors; 24/05/2012 9:44:54 88 High Impact Research Annual Report 2011 To develop a mathematical model ofthePMSMfromwhichatorque and flux expressions which are directly linked to the switching variablesofmultilevelinvertercan bederived To develop special control algorithms for low and high speed operations, and to use the developedalgorithmstoproducea drivewithwidespeedrange To develop a MLI-based DSC algorithm that uses the voltage timeintegraltoestimatethemotor flux and controls the voltage accordingtotheestimatedflux Methodology The implementation of the project will involve an intensive review of various hybrid multilevel inverter topologies, existing PMSM DTC concepts, and their control, this will be followed by modeling and simulation of the proposed topology and the development of the voltage control strategy. After that the power circuit will be designed to perform the experimental verification of the proposedtopologyandthecontrol algorithm Outcome New hybrid topology New introduction of DSC control for multilevel inverter and PMSM drives Possible High Impact Journals forPublications IEEE transaction on industrial electronics IEEE transaction electronics on power Renewableandsustainableenergy review Appliedenergy Collaborators mixed inverter Prof.DrPragasenPillay,Concordia University,Canada New capacitor balancing control algorithmfortheinverter Prof. Dr. Mutsuo Nakaoka, YamaguchiUniversity,Japan New voltage controlled drive modelandapproach Project No: UM.C/625/1/HIR/MOHE/ENG/18 Title: Undivided Redox Flow Battery Reactor Employing Porous Flow Through Electrodes and Deep Eutectic Solvents Principal Investigator : Dr. Mohammed Harun Chakrabarti Faculty : Department of Chemical Engineering, Faculty of Engineering SummaryofResearchProposal Thisprojectemphasizesuponthewastetoresourcesschemebyutilizingpalm shell waste to produce activated carbon electrodes for application in novel flowbatterydesigns.Theuseofionicliquidsanddeepeutecticsolventsmay berealizedinboththeelectrodepreparationstageaswellastheapplication of these exotic solvents in flow batteries themselves. The main aim is to improve the energy density of these batteries whilst maintaining their high charge/dischargeefficienciesattheleastpossiblecost.Thiswouldenable theirapplicationsaslargescaleenergystoragemarketsforpeakshavingas wellasinrenewableenergymarketinMalaysia. Objectives Develop novel electrodes from palm shell wastes (graphene basednanocomposites) Runsurfacecharacterizationtests ontheelectrodes Test the electrochemical characteristics of the electrodes in ionic liquids and deep eutectic solvents Apply these electrodes with optimum choice of ionic liquid or deepeutecticsolventsindifferent flowbatteryconfigurations HIR Annual report 2011.indb 88 Compare the performance of typical secondary batteries along withournovelflowbatterydesign Mathematical modeling of the electrode synthesis and flow battery operation would be conductedtooptimizetheprocess Methodology Upon the synthesis of novel graphene based nanocomposite electrodes, they will be characterizedbycyclicvoltammetry andchronoamperometry.Surface characterization may be done by means of EDX, SEM, TEM and otheranalyticaltechniques.Once best electrochemical conditions are identified, same electrodes wouldbetestedinionicliquidsand deepeutecticsolvents.Optimum configurations would be realized from which, charge/discharge experiments would be conducted withsmall-scaleflowcells.Scaleup would be realized based upon obtaining successful results from previous tests. Mathematical modeling would be conducted at 24/05/2012 9:44:54 High Impact Research Annual Report 2011 each stage to help in determining optimum conditions. From pilotscale, a full-scale commercial prototype would be proposed for storing renewable energy efficientlyinMalaysia 89 Possible High Impact Journals forPublications JournalofPowerSources ElectrochemistryCommunications ElectrochimicaActa Outcome ChemicalEngineeringJournal Application of excess palm shell wastetoproduceusefulelectrodes Collaborators Efficient storage of renewable energy in Malaysia (better than lead-acidbatteries) Dr. C. T. John Low (University of Southampton) A new prototype may be developed for implementation in hybridvehiclesinMalaysia ProfessorF.C.Walsh(Universityof Southampton) Professor Nigel Brandon (Imperial CollegeLondon) Professor Tom Welton (Imperial CollegeLondon) Project No: UM.C/625/1/HIR/MOHE/ENG/19 Title: Characterization of the Negative Bias Temperature Instability (NBTI) Impact on New-Age Deep-Submicron Devices to Effectively Predict System Failure Principal Investigator : Associate Professor Dr. Norhayati Soin Faculty : Department of Electrical Engineering, Faculty of Engineering SummaryofResearchProposal Inthefieldofelectronics,circuitlifetimeisamajorreliabilityissue.Intoday’s era,MOSFETsarethekeyreliabilitycomponentsinanelectronicsystem.The lifetimeofMOSFETdependsonmanyaspectsandNegativeBiasTemperature Instability(NBTI)isoneofthem.Thisoccursduetothenegativevoltageon p-MOSFETsinanelevatedtemperature.Therehasbeenlotsofresearchon thisregardforthelastfewdecades.But,daybydaytechnologyisadvancing towardsnanometerscaleandNBTIisbecomingaseriousconcernwhereits’ characterizationisdifficulttopredicttilldate.Thisdirectlyaffectsthecircuit lifetime.WeneedtounderstandNBTIdynamicsinordertopredictdeviceand hencesystemaging.Alongwiththis,NBTIrecoveryisoneoftheimportant featurestobetakencareofinordertoenhancecircuitlifetime. Objectives Aspertheresearchproblems,we havesetourinitialobjectivetocarry on an investigation on a suitable characterization method to make realisticextrapolations.Alongwith this, we will explore mathematical and statistical methods to have an accurate measurement of the defects which are subject as the adverse outcome of negative bias stress voltage under high temperature and which lead to NBTI degradation. Finally we will investigate the right stress HIR Annual report 2011.indb 89 conditions in such a way that the defect responsible for NBTI degradation is only accelerated and not to trigger other defect generationmodes Methodology In order to characterize NBTI initially we are supposed to go through a thorough literature review.Thesereviewworksmainly consist of theoretical modeling, simulation, device and circuitlevel mismatch. Along with these the physics of dynamic NBTI will be investigated, in order to have a transparent idea on AC characteristicsofNBTIdynamics Having gone through thorough review the next step will be to perform simulation on NBTI degradation by employing third generation Spice software which willsimulatecircuitlevelanddevice levelreliability.Thissimulationwill help us to obtain mathematical modeltopredictNBTIdegradation 24/05/2012 9:44:54 90 High Impact Research Annual Report 2011 After we attain a mathematical model a calibration will take place to get the real time data and to verify the model obtained earlier from simulation process. A calibration will be done by MOSFET characterization tool where we will do the experiment consideringanenvironmenthaving anelevatedtemperature.Basedon ourreviewstudyondynamicNBTI we will characterize the effect of ACsignalandNBTIonp-MOSFET Lastly we will optimize the effectivemeasurementtechniques to characterize the recovery of the system lifetime degradation occurredbytheeffectofNBTI Outcome The possible outcomes include the exploration of the impact of NBTI degradation on parameters of CMOS transistors. This explorationwillincludetheanalysis of threshold voltage shifts, drain current degradation and interface trap concentration. After our researchwehopetodeterminethe dependence of NBTI degradation on measurement methods, temperature stress and process conditions. Analysis of practical implications of NBTI degradation can be predicted by developing experimentally justified novel algorithms Possible High Impact Journals forPublications IEEE Transactions On Electron Devices IEEEElectronDeviceLetters Physics,AppliedLetter MicroelectronicReliability MicroelectronicEngineering Collaborators Professor Dr. Ang Ding Shenp; NanyangTechnologicalUniversity, Singapore ProfessorDr.J.F.Zhang;Liverpool JohnMooresUniversity,UK Project No: UM.C/625/1/HIR/MOHE/ENG/20 Title: Production of Hydrogen by Hydrolysis of Biomass Principal Investigator : Dr. Jaya Narayan Sahu Faculty : Department of Chemical Engineering, Faculty of Engineering SummaryofResearchProposal Hydrolysis, gasification, pyrolysis, and catalytic pyrolysis of biomass are identifiedasthepromisingandcompetitiveroutesforproducingrenewable hydrogen, although other bioenergy technologies have been developed. Biomasswastehydrolyzedintohighvalue-addedproductsisapracticaland effectiveway.Currentindustrialhydrolysismethodsofbiomasswasteinclude chemical (acid, alkali or catalytic) hydrolysis and enzymatic hydrolysis. But the chemical hydrolysis needs violent reaction conditions and often brings seriouspollutionoftheenvironment.Enzymatichydrolysisisexpensive,and withlongproductioncycle.Therefore,theidentificationanddevelopmentof a new environment-friendly method to overcome the shortcomings of the chemicalandenzymatichydrolysisisparticularlyimportant. Objectives Most of biomass waste is easily hydrolyzed in super- or subcritical water, which is structurally different from normal liquid water, and possesses some marvelous properties: first, it behaves like HIR Annual report 2011.indb 90 non-polar organic solvent (similar withacetone) Thus it can substitute for some of organic solvents, and become a clean medium for chemical reactions; second, it has density fluctuation, low dielectric properties,andmolecularclusters, thus it can become an effective medium for energy and mass transfer; third, its ionic product (H+andOH-)isthousandsoftimes 24/05/2012 9:44:55 High Impact Research Annual Report 2011 higher than normal water, thus it can take on a powerful catalysis based on acid and alkali at the same time, and it also can be a solvent or reactant participated in chemical reaction. Therefore, reaction rate can be accelerated in super- or sub-critical water. Without any pollution, hydrolysis insuper-orsub-criticalwaterisan environment-friendly technology. The biomass and waste can be hydrolyzed into high value industrial raw material: amino acid, unsaturation fatty acid, oil, polysaccharide, hydrogen and methaneandsoon Methodology Outcome The investigation of this research is divided into three phases. The firstwillbeconcernedtoSelection of biomass at different operating condition,locallyavailablebiomass wastesuchaspalmshell,coconut shell, rice husks, coirpith, saw dust, banana pith, banana stem, and orange peel will be screened for its bio-oil capacity, while the second phase is hydrogen production test in a fluidizedbed reactor and the third phase is the optimization and process control for real industrial application in a pilotplantandmodelling The project’s goal is to promote the development and use of environmentally beneficial technologies through obtaining independent and credible performance evaluations of commercially-ready green fuel technologies in Malaysia. The results from this project will allow a reappraisal of the competing theories and practical technology of hydrogen production development not only in the Malaysia,butglobally a) b) c) HIR Annual report 2011.indb 91 Synthesis of bio-oil in batch process: Synthesis of biooil at different chemical/ mechanical heat treatment. i.e. microwave radiation power or conventional thermal power, steam ratio, reaction time, solid/solvent catalystdoses Synthesis of Hydrogen in continuous fluidizedbed reactor: The hydrogen production test of different biomass in continuous mode fluidizedbedreactorwithand withoutcatalyst ProcessControl,optimization and modelling: All process variables are control and optimization for high yield of hydrogen conduct for batch and continuous. Modelling work will be conducted for continuousmodeofoperation in a pilotplant for hydrogen production of different biomass and sustainability studiesforlifecycle 91 Possible High Impact Journals forPublications International Journal of hydrogen Energy BioresourceTechnology BiomassandBioenergy ChemicalEngineeringJournal FuelProcessingTechnology Collaborators Prof.K.K.Pant,IndianInstituteof Technology(IIT)NewDelhi,India Prof.B.C.Meikap,IndianInstitute ofTechnology(IIT)Kharagpur,India Dr. Ujjal Kumar Ghosh, Curtin University,Sarawak Prof. Anand V. Patwardhan, Institute of Chemical Technology (ICT),Mumbai,India Prof. V.K. Srivastava, ABES IT group of institutions, New Delhi, India 24/05/2012 9:44:55 92 High Impact Research Annual Report 2011 Project No: UM.C/625/1/HIR/MOHE/ENG/21 Title: Phase Change Material (PCM) for Energy Storage System Principal Investigator : Dr. Hendrik Simon Cornelis Metselaar Faculty : Department of Mechanical Engineering, Faculty of Engineering SummaryofResearchProposal Drasticallyofpopulationgrowthandindustrialrevolutionleadingtheincreasing gapbetweentheglobaldemandandsupplyofenergy.Theperiodicfeature of renewable energy such as solar has become a major barrier in the wide spreadinguseofthisenergy.Thesolutiontothisbarrieristheusageofenergy storage system which store energy during the day and release energy at night.Basically,therearethreemethodsofstoringthermalenergy:sensible, latentandthermo-chemicalheatorcoldstorage.Latentheatthermalenergy storagesystemwhichutilizesphasechangematerials(PCMs)toabsorband release heat is widely used. When the energy source is available, PCMs is heatedandabsorbtheenergyforphasetransition(suchasfromsolidphase toliquidphase).Whentheenergyisneeded,liquidischangedbackintosolid byreleasingheat.Alargeamountofheatcanbeabsorbedandreleasedat constanttemperaturebyusinglatentheatthermalenergystoragesystemand its size is smaller than sensible heat thermal energy storage. Therefore, to overcome the potential shortage of energy one of the alternative solutions istodevelopenergystoragedevicesbyfindingasuitablematerialtostore energy. The energy storage leads to saving of premium fossil fuel. Phase changematerials(PCMs)attractattentionasoneofpotentialthermalenergy storage system due their higher energy storage densities and isothermal phasetransition.PCMhasbeenusedformanyapplicationswhichincluded thermal comfort, electronic cooling, space craft, water heating, building, and etc. Due to this reason, this study attempt to investigate potential of energyperformanceimprovementthroughselectedphasechangematerials for thermal heat storage system which will be used in solar collector. Nanocapsulecontainingsolid/liquidphasechangematerialsornanoparticle enhancedphasechangematerials(NEPCM)hasbeenproposedtobeusedin thethermalenergystorage.Forexperimentalpurpose,twotypesofpopular techniques are used for the measurement of fusion latent heat and PCMs melting temperature, which are the differential thermal analysis (DTA) and thedifferentialscanningcalorimeter(DSC).However,experimentalapproach requiresthesamplesofNEPCM.Thecommontechniqueisthephysicalgasphase condensation or chemical synthesis technique which involves the evaporation of a source material and the rapid condensation of vapor into nanometer sized crystallites in a cool, inert, reduced-pressure atmosphere. NEPCMcanbeformedbypropersuspensionofthesenanoparticlesintoa PCM.Inthisresearch,theefficientmodelingandsimulationstrategyofthe heat transfer process for the selected NEPCM will be established. Both solidificationandmeltingphasetransitionisincludedinthestudy. TheheattransferbehaviorsforthematerialsareinvestigatedandtheNEPCM which demonstrates the best performance is proposed for the usage in energystoragesystem.Theresultswillbeverifiedbyexperimentalfindings foraccuracy. Objectives Methodology Outcome To investigate the theoretical and experimental energy storage on selectedphasechangematerials Literaturereview: Outputsexpected 1 stage: Phase change material developmentandtesting st To design an experimental rig of energycollectorforselectedphase changematerials 2nd stage: development To characterize the thermal and melting heat transfer in selected types of thermal storage system using combination of phase change materials for various renewableenergysources 4th stage: Optimization/further improvement HIR Annual report 2011.indb 92 Heat exchanger 3rdstage:Exergyandthermalheat transferanalysis • Distinguish the physiochemical properties and thermal analysis by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), differential thermal analysis (DTA) and thermomechanical analysis 24/05/2012 9:44:55 High Impact Research Annual Report 2011 (TMA) for energy storage on selected phase change materials • Development and design an experimental rig of renewable energy collector on selected phase change materials. • Show the thermal and melting heat transfer characterize analysis for thermal storage system usingcombinationofphase changematerialsforvarious renewableenergysources. • Perform the potential energy optimisation and improvementoftheselected phasechangematerialsand thecombinationforthermal heatstoragesystem. Infrastructuralcontributions Cells(3.858) Newphasechangematerial(PCM) and thermal storage lab with equipmentsandfacilities Energy(2.952) • Environmental Chamber • Differential Calorimeter Test Scanning • ThermogravimetricAnalyzer • Viscometer • FTIRSpectrometer Possible High Impact Journals forPublications Renewable & Sustainable Energy Reviews(If2009=4.842) Solar Energy Materials And Solar 93 International Journal Of Heat And MassTransfer(1.947) International Journal Of Thermal Sciences(1.770) AppliedEnergy(2.209) Collaborators Hamdani Umar, Syiah Kuala University,Acheh,Indonesia Irwansyah Idram, Syiah Kuala University,Acheh,Indonesia Prof Dr Hadi Nur, University of Technology Malaysia, UTM, Malaysia Prof Dr Ayhan Demirbas, Sirnak Universitesi Rektorlugu, Turkey Project No: UM.C/625/1/HIR/MOHE/ENG/22 Title: Hybrid Solar Energy Research for Rural Electrification Principal Investigator: Associate Professor Dr. Hew Wooi Ping. Faculty : Department of Electrical Engineering, Faculty of Engineering SummaryofResearchProposal About 93.1% of Malaysian households has access to electricity which is providedthroughthenationalgrid.InSabahandSarawakthereisalimited access to electricity mostly due to inaccessible communication and the access recorded in Sabah is 85% while in Sarawak it is recorded at 90% (RegionalReport,UNDP2007).ThataccesstoelectricityisrelatedtosocioeconomicdevelopmentshasbeenindicatedbystudiesinMalaysia(Regional Report, UNDP 2007). Therefore rural electrification is an essential step to create socio-economic activities and uplifts the income level in the rural communities so that when Malaysia has achieved the developed status in 2020,theruralcommunitiesarenotneglected. DuetothedistancefromtheNationalGrid,itisnoteconomicaltouseTNB supplies for most rural areas. The feasible solution is using solar energy coupledwithotherrenewablesourcessuchaswindorhydrosoastoproduce a stable source of electricity supply. The combination and control of these renewable energy sources depends on the site’s physical terrains and the weatherconditions. Objectives Using mathematical modeling, we hope to develop a better understanding of factors that influence the generation, transmission and distribution of electricity in the rural areas of Malaysia. A laboratory prototype HIR Annual report 2011.indb 93 Methodology will be designed and constructed to verify and investigate some of actual implementation problems. Asmallscaleactualsitemodelwill beinstalledtoverifythefeasibilities oftheproposedsystem Actual weather and physical terrain data for a remote village in peninsular Malaysia will be obtained and used to model a hybrid solar energy powered single phase electrical power generation, transmission and 24/05/2012 9:44:55 94 High Impact Research Annual Report 2011 distribution system. Various approaches to maximize the power output will be used to obtain the optimum renewable energy sources combination and management to achieve a stable electricity supply irrespective of the load requirements. Various Maximum Power Point Tracking techniqueswithArtificialIntelligent featureswillbeappliedtoachieve this. The load flow pattern and electrical faults will be detected and if necessary, automatic load sheddingandfaultisolationwillbe activated Possible High Impact Journals forPublications Outcome Professor Hideaki Ohgaki, Kyoto University,Japan Better understanding of rural electrificationinMalaysia Electrical design generators/machine Energypolicies Convertertopologies Pico-smartgridsystems Collaborators Prof. Ooi Boon Teik, McGill University,Canada Prof. Emil Levi, Liverpool John MooreUniversity,UK Mathematicalmodelscanbeused to study the impact of weather conditions and physical terrains on the generation, transmission and distribution of electricity from renewableenergysources Project No: UM.C/625/1/HIR/MOHE/ENG/23 Title: Hydrogen Refueling Station and Dispenser Control System Principal Investigator : Dr. Mahidzal Dahari Faculty : Department of Engineering Design & Manufacture, Faculty of Engineering SummaryofResearchProposal Hydrogenisthesimplestelementknowntoexist.Anatomofhydrogenhas oneprotonandoneelectron.Hydrogenhasthehighestenergycontentofany commonfuelbyweight,butthelowestenergycontentbyvolume.Itisthe lightestelementandagasatnormaltemperatureandpressure.Hydrogenasa gas(H2)howeverdoesn’texistnaturallyonearth.Itisfoundonlyincompound form. Combined with oxygen, it would be water (H2O), whilecombined with carbonitwouldformorganiccompoundssuchasmethane(CH4),coal,and petroleum.Hydrogenisahigherefficiencyandlowpollutingfuelthatcanbe usedfortransportation,heating,andpowergenerationinplaceswhereitis difficulttouseelectricity.Sincehydrogengasisnotfoundonearth,itcanbe manufactured using three primary methods i.e., use of a reformer, a direct methanolfuelcell,andanelectrolyzer. The commercialization of gaseous hydrogen fueled vehicles requires both the development of hydrogen fueled vehicles and the establishment of a hydrogen fueling infrastructure. These requirements would create a circular cause and consequence, that manufacturers will not build and consumers will not buy vehicles without an adequate refueling infrastructure, whilst potentialrefuelingstationoperatorswillnotinvesttheneededcapitalwithout anadequatemarkettoserve. Since the development of a hydrogen refueling infrastructure is a critical elementtotheintroductionoffuelcell-poweredvehicles,aflexibleandlowcosthydrogenrefuelingtestrigusingsolarpoweredisproposed.Itisflexible due to its ability to accept hydrogen from the three available methods and HIR Annual report 2011.indb 94 24/05/2012 9:44:55 High Impact Research Annual Report 2011 95 be easily adapted to future renewable hydrogen production system. The design is expected to be scalable for accommodating future growth which couldbeeasilyintegratedtoliquidhydrogenrefuelingwithfewmodifications andminimaladditionalinvestment.Alongwithallthebuilt-inbenefitsofthe station,innovativestandardsandpublicawarenesscampaignareplannedto encouragetheacceptanceofhydrogenasafuel,whilesupportingthenational ongoingfuelcell-poweredvehicledevelopmentprogram.Withtheoperation of this facility to begin in 2011, it will be the first step in developing the commercialhydrogeninfrastructureoftomorrow,hereinUniversityMalaya. Objectives Methodology Outcome Introducing a new hydrogen refueling algorithm based on renewable energy process by considering the electrolysis analysis and renewable energy as afundamentalmodel. WhensolarpowerfromthePVarray is unavailable or insufficient (e.g., duetocloudcover,etc.),electricity from the grid is used for the electrolysis process. The system, when running exclusively on solar energy,couldproduceabout2,000 liters (approximately at 30 bar) of gaseous hydrogen per year which is enough to fuel hydrogen or fuel cell vehicle. By using both solar power and electricity from the grid, the station’s production capabilityisexpectedtobe24,000 liters per year, whilst cars could befueledattherateof5litersper minute. Hydrogen fuel (in the gas form) would be dispensed to the hydrogen vehicle (hybrid or fuel cell) using a unique fast-fill and multi-bankcascadesystem A test rig of hydrogen refueling station that can be used to study hydrogenrefuelingandproduction systemwhichcomprisesofseveral componentssuchas:- A data acquisition system and mass flow sensor would record the amount of fuel delivered. Several new technologies would be introduced to the test rig. An innovativepurewaterrecirculation system would keep the water losses in the electrolyzer at a minimum consumption rate. The control system would maximize thehydrogenproductionefficiency by regulating fluctuations in electric power production caused by changes in sunlight intensity. Consequently, research on minimizing the energy losses associated with producing hydrogenusingsolarenergywould be carried out. One of the unique featuresofthisadvancedhydrogen refuelingtestrigisitsnearlysilent operation and its visual impact; it promotes a “customer-friendly” image with its graceful canopy designanditscompactandeasyto-operatefeatures x. Developingacomputersimulation modeltorepresentanelectrolysis measuring system which is used as a tool for re-evaluating andredesigning the hydrogen refueling algorithm i. SupplyStorageSystem ii. DispensingSystem iii. CarStorageSystem iv. Recycling System v. DataAcquisitionSystem and Make-up vi. Distributed Control MonitoringSystem and vii. Test Rig and Instrumentation System viii. FuelReformingSystem ix. CompressorSystem FlowMeteringSystem Possible High Impact Journals forPublications International Journal Of Hydrogen Energy(ISSN:0360-3199) Renewable Energy (ISSN: 09601481) JournalOfProcessControl (ISSN: 0959-1524) Control Engineering (ISSN:0967-0661) Practice IEEE Transactions On Control SystemsTechnology (ISSN:10636536) Collaborators Assoc.Prof.Dr.MohamedIbrahim B.AbdulMutalib(UTP) Assoc. Prof. Dr. Nordin B. Saad (UTP) Assoc. Prof. Dr. Daisuke Kurabayashi (Tokyo Institute of Technology). HIR Annual report 2011.indb 95 24/05/2012 9:44:55 96 High Impact Research Annual Report 2011 RESEARCH PROPOSAL (HIR-MoHE5Years) FacultyofScience Project No: UM.C/625/1/HIR/MOHE/SC/01 Title: Femtosecond Laser and Terahertz Generation for Photonics Applications Principal Investigator : Professor Dr. Harith Ahmad Faculty : Department of Physics, Faculty of Science SummaryofResearchProposal Terahertz (THz) wave refers to electromagnetic waves propagating in frequencyrangebetween300GHzand3THz,correspondingtowavelength regionfrom0.1mmto1.0mm.Itischaracterizedbyitsnon-ionizingnature and are transparent to most non-conducting materials while not able to penetrate metals and water. These characteristics have raised the interest in research for terahertz wave generation and detection for applications in securities,spectroscopyandTHzsensing.CurrentmethodofTHzgeneration relieson synchrotron and bulk femtosecond laser as excitation source. It is therefore important to research methods of THz wave generation using alternative cost effective solutions such as fibre-based femtosecond laser, differencefrequencymethodusingdualwavelengthlasersourceandhighly nonlinear optical materials such as bismuth-doped waveguides and other approachesthatarenovelandmeetingtheendobjective. Objectives Methodology To develop excitation sources for terahertz (THz) generation. The sourcesunderstudyincludefibrebased femtosecond lasers, dual wavelength lasers. To research the generation of THz wave using highly nonlinear optical materials such as bismuth based glasses. To set up a THz generation and detectionsystem,andtogenerate THz wave using the proposed excitationsourcesandmaterials Excitation sources for the generation of THz wave will first bedeveloped.Theseincludefibrebased femtosecond laser and dual-wavelength laser. Research on potential new materials with high nonlinearity will be carried out. Nonlinear phenomena in the materialssuchassupercontinuum generation and wavelength conversion will be studied. Development of THz generation and detection system will be carried out. Performance of THz generation using the proposed excitation sources and materials willbecharacterized Possible High Impact Journals forPublications IEEEPhotonicsTechnologyLetters JournalofSensorsandActuators OpticsExpress OpticsLetters AppliedPhysicsLetters Collaborators Douglas Paul, Glasgow,UK University of MarcSorel,UniversityofGlasgow, UK DominiqueCoquillat,Universityof Montpellier,France Outcome Understanding of THz generation anddetectionprinciple Development of compact THz source HIR Annual report 2011.indb 96 24/05/2012 9:44:55 High Impact Research Annual Report 2011 97 Project No: UM.C/625/1/HIR/MOHE/SC/02 Title: Fuctional Molecules for Life-style Diseases Principal Investigator : Professor Datin Dr. Sri Nurestri Abd Malek Faculty : Institute of Biological Sciences, Faculty of Science SummaryofResearchProposal Humankind is plagued by a number of diseases many of which are lifethreatening like neurodegenerative diseases, diabetes, cardiac arrests and cancer.Thesediseasesarearesultofourlifestyleandexposuretopolluted environmentcontributedbyindustrialization.Thoughmanydrugsareavailable thequalityoflifeisjeopardizedinmanycases.Toaddtotheburdenisthe risingcostofhealthcare. Our strategy now is prevention rather than cure. We are now looking at functional molecules from plants and mushrooms (a number of which are includedinourdiet)topreventorreducetheoccurrenceofthesediseases in humans. Further, the quality of life of those who are ill and on lifelong therapeutic drugs may be enhanced by using functional molecules from plantsandmushrooms. Whatweneedtodonowistovalidatetheseclaimsbyscientificstudies.The investigationsoftheextractsandpurecompoundsatmolecularandgenomic levels will help us understand how these functional molecules function in cells. The interaction between drugs or functional molecules and the major carrierproteinofmammalianbloodcirculationplaysanimportantroleinthe pharmacologyandpharmacokineticsofthedrugs.Thesefindingswillhelpin drugdesign,drugefficacyevaluationandthebestmodetodelivertheactive ingredient to prevent, reduce incidence or cure diseases. The molecules canbedeliveredasasolecomponentorinacocktailtotapthesynergistic effects of these molecules for maximum benefit to the body. The scientific datafromourstudiescanhelpintheacceptanceofcomplementarymedicine bydoctors. Objectives Methodology Outcome To identify functional molecules frombiodiversityforthetreatment of diabetes, hypertension, cancer andneurologicaldisorder The methodolgies employed will be based on either standard established protocols or those modified and in current applications in the labs involved in this project. Bioactive primary andsecondarymetaboliteswillbe isolated and purified from plants and mushrooms using standard techniques Better understanding of how functional molecules function in cells To investigate and validate the mechanismofactivityoffunctional molecules at molecular and genomiclevels To study stability and interactions offunctionalmoleculeswithtarget site To manipulate microorganisms for enzyme production and applications in production of potentialfunctionalmolecules HIR Annual report 2011.indb 97 These metabolites and active extracts will be screened for their potential activity in preventing or reducing lifestyle diseases such as neurodegenerative diseases, diabetes, cardiac arrests and cancer. Useful enzymes will be utilised in the production of potential functional molecules. Binding studies between functional molecules and human serum albumin would be studied by isothermal titration calorimetry(ITC)andfluorescence spectroscopy, as described elsewhere Scientific data from our studies can help in the acceptance of complementary medicine by doctors Possible High Impact Journals forPublications JournalofNaturalProducts Journal of Agricultural and Food Chemistry JournalofEthnopharmacology JournalofBiologicalChemistry Evidence Based Complementary andAlternativeMedicine FoodChemistry Collaborators Prof Dr. Aparna Dixit (Jawaharlal NehruUniversity,NewDelhi) 24/05/2012 9:44:55 98 High Impact Research Annual Report 2011 Prof Dr. Rajiv Bhat (Jawaharlal University,NewDelhi) ProfDrRogerKeynes(Cambridge University,UK) Prof Dr. Bharat B. Aggarwal (Department of Experimental Therapeutics, Cytokine Research Laboratory,theUniversityofTexas MD Anderson Cancer Center, Houston,USA) Project No: UM.C/625/1/HIR/MOHE/SC/03 Title: Metal-organic frameworks for luminescence and nanoparticle generation Principal Investigator : Professor Dr. Edward R.T. Tiekink Faculty : Department of Chemistry, Faculty of Science SummaryofResearchProposal Thisresearchpivotsaroundtheexploitationoffunctionalizedthiolateligands, for example by including hydrogen-bonding functionality and/or multiple metal binding sites, and their complexation by multifunctional bipyridinetype bases will lead to the generation of novel materials with applications as luminescent materials, MOF’s, and as synthetic precursors for metal sulphide nanoparticle production. This proposal is designed to overcome thegenerallackofcontroloversupramolecularaggregationbytailoringthe functionality and denticity of the ligands employed to assemble the metal 1,1-dithiolate synthons in the solid-state. The principles developed in this research will have general applicability and therefore will form a secure foundationforrelatedstudiesundertakenbyotherresearchers.Thetailored materials will exhibit solid-state luminescence and different supramolecular architectureswillallowfine-tuningofemissionproperties.Selectedsystems willbeevaluatedfortheirpotentialassyntheticprecursorsformetalsulphide nanoparticlegenerationofspecificsizeandmorphology.Theapplicabilityof post-syntheticmodificationofselectedmaterialswillbeinvestigatedincases wheretheperipheralfunctionalityissuitableforsubsequentreactiontoallow, forexample,hydrogenbondingtobesubstitutedbycovalentinteractions. Objectives To rationally design metal thiolate species of specific dimensions (0-, 1-, 2- and 3-D) employing covalent,secondaryandhydrogen bondinginteractions, To correlate supramolecular architectures with solid-state luminescenceresponses, To increase the dimensions of synthesised aggregates by postsyntheticmodification, To correlate synthetic precursor structure with generated nanoparticles, To investigate cognate ligands, their metal complexes, HIR Annual report 2011.indb 98 incorporating both transition metal, main group elements, lanthanides and actinides, and to establishtheirpotentialtofacilitate supramolecular assembly and to generatefunctionalmaterials Methodology Using principles of chemistry and a full range of physiochemical characterisation techniques, the aims of this project above will be realized primarily by adding metal coordinating functionality and/ or hydrogen bonding potential to the 1,1-dithiolate ligands, and by increasingthecoordinationsiteson thebases.Whileinitiallyourfocus will be upon zinc(II), cadmium(II) and tin(IV) salts, owing to their easeofhandlingandcoordination flexibility,ourstudywillbedirected towards rationally designed supramolecular architectures with transition metal nodes so as to extend our chemistry and potential applications (e.g. magnetochemistry) further. Typically, metal complexes will be prepared via metathesis between ametalsaltandthethiolateligand. Subsequently, adducts will be synthesizedbyrefluxingthemetal saltinthepresenceofthechosen bases 24/05/2012 9:44:55 High Impact Research Annual Report 2011 Outcomes The specific outcomes of this researchprogrammeareexpected tobe i. the generation of new functional photoluminescencematerials ii. the generation of novel synthetic precursors for nanoparticlesgeneration iii. the development of an overarching principle for the designofMOF’s iv. theformationofnewmaterials for gas (e.g. hydrogen) storage v. thedevelopmentofprinciples for post-synthetic chemical modification vi. the development of novel materials and synthetic protocols 99 Possible High Impact Journals forPublications Chemical Communications CrystEngComm Crystal Growth & Design Dalton Transactions Inorganic Chemistry Collaborators Prof.DrIonelHaiduc,Universitatea Babes-Bolyai Prof. Dr Kieran Molloy, University ofBath Prof. Dr Jan Reedijk, Universiteit Leiden Prof.DrVivianWing-WahYam,The UniversityofHongKong Prof. Dr Julio ZukermanSchpector, Universidade Federal deSãoCarlos Project No: UM.C/625/1/HIR/MOHE/SC/04 Title: Molecular Devices for Nanoscale Applications Principal Investigator : Professor Dr. Yatimah Alias Faculty : Department of Chemistry, Faculty of Science SummaryofResearchProposal The nanoscale science and engineering have shown great promise for the fabricationofnovelnano-sensorswithfasterresponseandhighersensitivity than that of planar sensor configurations, due to their small dimensions combinedwithadramaticallyincreasedcontactsurface,andstrongbinding withbiologicalandchemicalreagents.Biosensorshavebeenemployedasan alternativeforrapidmeasurementofbodymetabolitessuchasglucose,urea, anduricacid.Mostcommerciallyavailablebiosensorstripsexploitenzymes asthemainrecognisingagenttogiveselectivity.Enzymes,beingproteinin nature, denatures at room temperature, undergoing structural changes due to environmental influence. Furthermore, when immobilised on sensing electrodesurface,certainactivegroupsoftheenzymeformcovalentbonding, whichcanresultinthelossofcriticalfunctionswhichsignificantlydecreases theaccuracyofenzymaticbiosensors. Developmentofmolecularcapsulesbyanionicp-sulfonatocalix[4,5]arenesin abowlshapedconfigurationofferstheirpotentialapplicationsinseparation technologyandsensors.Theconfinedguestmoleculeshaveinherentlyweak interactions involving hydrogen bonding and π-stacking, which presumably contributes to the formation and stabilisation of the capsules within the extended structures. Such calixarenes are also effective in accommodating a wide range of guest molecules in their cavities, including crown ethers, aminoacidsandnucleicacidbasesanditsderivatives.Weproposedesign and prototype of molecular sensing devices for bio-chemical nano-sensors for bio-medical and health applications. Our nano-sensors can be used to monitor health conditions by monitoring glucose, uric acid, urea, calcium, potassiumandchloridewhicharerelevanttoourbodymetabolites HIR Annual report 2011.indb 99 24/05/2012 9:44:55 100 High Impact Research Annual Report 2011 Objectives Methodology Outcome Todesignandmodifyfunctionalised heterocyclicaromaticmonomers In order to achieve our specific objectives and deliverables, we have identified the following researchmethodology: Atleast20Tier1ISI-publications To design and demonstrate the versatility of p-sulfonatocalix[4] areneasmolecularcapsule To fabricate multifunction nanosensors based on non-enzymatic materials To evaluate the performance of fabricatednanosensors Design of Molecular Sensing Device During the first stage we employ molecularmodellingandsimulation inordertodesignmacromolecular that potentially binds or interacts withthetargetanalytes Fabrication of Molecular Sensing Device Nano-electrodes would be fabricated using chemical vapour deposition (CVD) method, though selective deposition, nanolithographyandetching Non-enzymatic glucose sensor system based on functionalised polythiophene nanoparticles and nanowires Molecular capsule based on p-sulfonatocalix[4]arene Possible High Impact Journals forPublications OrganicLetters Journal of American Chemical Society Journal of Communication Chemical CharacterisationandPrototypesof MolecularSensingDevice NewJournalofChemistry Molecular junction bridging of two nano-electrodes can be conveniently used to detect the presence of ions, using conductometricmethod Collaborators Systemprototyping The system-level deliverables are complete units of integrated sensor array, readout circuitry, signal processing and filtering hardware, microcontroller, wireless transmitter and receiver and principal component analysis software and application firmware. All these components are fabricated on a common PCB board to fit miniaturized low power portable devices, equipped with LCD display units and wireless options. These prototypes are user-friendly units fordemonstrationpurposes HIR Annual report 2011.indb 100 5PhDand10MasterStudents FaradayDiscussion Prof. Chris Hardacre, QUILL/ Queen’sUniversity,Belfast,UK. Prof. Colin Raston, Centre of Strategic Nano-Fabrication, SchoolofBiomedical,Biomolecular and Chemical Sciences/University ofWesternAustralia,Australia 24/05/2012 9:44:55 High Impact Research Annual Report 2011 101 Project No: UM.C/625/1/HIR/MOHE/SC/05 Title: Bioorganic and Medicinal Chemistry and Organic Synthesis Principal Investigator : Professor Dr. Kam Toh Seok Faculty : Department of Chemistry, Faculty of Science SummaryofResearchProposal Discovery and exploitation of bioactive secondary metabolites from indigenous plant and microbial sources, including investigations of aspects ofstructure,biogenesis,bioorganicandmedicinalchemistry,modeling,and synthesis. Objectives Methodology To implement total and partial synthesesofselectedalkaloidand oligostilbenoidderivatives Extensive screening followed by isolation (small to large scale) of novel or bioactive secondary metabolites from plants and microbes (actinobacteria and fungi) To discover bioactive metabolites from plants and microbes (actinobacteria and fungi) and to investigate the bioorganic and medicinalchemistryaspectsofthe activeprinciples To implement syntheses of flavonoidandchalconederivatives in connection with a study of the mechanism of serine proteaseligandinteractionandactivity To investigate reaction pathways involved in the electrochemical oxidationofindolederivativesand 1,2-disubstitutedalkenes To exploit anodic oxidation as a key step in the synthesis of various naturally-occurring tetrahydrofurans, indanes, dihydronaphthalenes, and oligostilbenoids SynthesisofBioactivePrinciples Bioactive Principles from Microbes – At present a virtually underexploited source of useful compounds Better understanding of the mechanism of serine proteaseligandinteractionandactivity Structure studies of selected compounds, which are of interest from viewpoint of novel molecular architecture, biogenesis, or biologicalactivity Possible High Impact Journals forPublications Investigations of bioorganic and medicinal chemistry aspects of activeprinciples Journal of Organic Chemistry (J. Org.Chem.) OrganicLetters(Org.Lett.) Exploration and development of biomimetic syntheses of selected targets Journal of Natural Products (J. Nat.Prod.) Electro-organicstudiesofselected compounds PlantaMedica(PlantaMed.) Outcome Tetrahedron New Compounds with Novel Structural Frameworks and BiogeneticImplications Tetrahedron Letters (Tetrahedron Lett.) NewBiologicalEffects Bioorganic and Medicinal Chemistry Letters (Bioorg. Med. Chem.Lett.) Associated Bioorganic Chemistry Studies Phytochemistry Organic and Biomolecular Chemistry(Org.Biomol.Chem.) Chemistry-AnAsianJournal Bioorganic and Medicinal Chemistry(Bioorg.Med.Chem.) HIR Annual report 2011.indb 101 24/05/2012 9:44:55 102 High Impact Research Annual Report 2011 Project No: UM.C/625/1/HIR/MOHE/SC/06 Title: Synthesis and Application of Low Dimensional Materials. Principal Investigator : Professor Datin Dr. Saadah Abdul Rahman. Faculty : Department of Physics, Faculty of Science. SummaryofResearchProposal Lowdimensionalsystemsreferstomaterialswithastructurethatextendsto lessthanthreedimensions,withlatticestructuresthatcanresemblesheets, needles, thin films, or dots in nanometer-scale range. The low-dimensional structures are synthesized from organic and inorganic materials including carbon-based,metal-oxide-based,andnitride-basedsemiconductors.Such materialscanbeincorporatedinfabricationofhigh-performanceandenergyeffcient “green” optoelectronic and electronic devices such as organic and inorganic light-emitting diode (LED), laser diode (LD), photo diode (PD), solarcells,andtransistors.Theincorporationoflowdimensionalstructures significantlyenhancestheperformanceofeachofthedevices. Objectives Methodology The project is to synthesis/ grow, investigate and optimize properties of low-dimensional organic and inorganic thin-films and nanostructures. Additionally, the project aims to fabricate and optimize advanced electronic and optoelectronic devices incorporating material-engineered low-dimensional structures. Metal organicchemicalvapordeposition (MOCVD)systemisverycriticalfor thisprojectasitistheonlyproven technique for epitaxial growth of high-quality single-crystalline materials. The major novelty for MOCVD growth in this project is thatthethin-filmswillbegrownon low-cost silicon substrate instead ofexpensivesapphiresubstratein conventional techniques by most other research groups elsewhere. The novelty would allow for the realization of next-generation advanced optoelectronic and electronic devices at significantly lowcost The research will be carriedout in four sub-projects, comprising, (i) synthesis and growth of low dimensional materials, (ii) characterizations of low dimensional materials, (iii) fabrication of advance optoelectronic and electronic devices incorporating low dimensional structures, and (iv) optimization of devices performance by materials engineering. In synthesis and growth sub-project, various low dimensional structures will be synthesized/grown by optimizing the MOCVD growth parameters, such as gas/vapor type, gas/ vapor ratio, gas/vapor flow rate, growthtemperature,andchamber pressure. Subsequently, the material characterization subproject will include investigation ofstructural,opticalandelectrical properties, surface morphology, crystal quality, compositional profiles, defect analysis, crosssectional thickness, etc, using advanced characterization techniques such as scanning electron microscopy (SEM), photoluminescence (PL), atomic force microscopy (AFM), Hall measurement, x-ray diffraction (XRD), and transmission electron microscopy (TEM). In device fabrication sub-project, the synthesized/grown thin-film structure will be fabricated into operational devices, such as, organic and inorganic lightemitting diodes, solar cells, laser diodes, photo diodes, and transistors.Thefabricationprocess HIR Annual report 2011.indb 102 will include photolithography, etching, metallization and hightemperature annealing. Finally, in device optimization sub-project, the properties of each thin-film layer in the device structure will be further optimized to obtain high-performance energy-effcient devices. Advanced material engineering techniques such as modulation doping, strained-layer superlattices, lateral epitaxial overgrowth and pendeo epitaxial overgrowth would be beneficial to significantly improve device performanceandefficiency Outcome The materials synthesis/ growth method in this project would open up possibilities for innovative development of various novel low-dimensional structures and nanostructures. The MOCVD epitaxial growth technique in this project enables innovative exploration in thin-film growth such as strained-layer superlattices(SLS),multi-quantum well (MQW), quantum-dot (QD), distributed Bragg reflector (DBR), multilayer(ML)thin-filmstructure, andnano-structures.Theadvance low-dimensional structures and nanostructureswouldenhancethe performance optoelectronic and electronic devices. The project is the fundamental approach for the growth and fabrication of energyefficient “green” devices such as high-bright ligh-emitting diode (HB-LED) for high color rendering 24/05/2012 9:44:55 High Impact Research Annual Report 2011 index (CRI) light source, shortwavelength laser-diodes (LD) for high-density storage, broadsensitivity photo-diodes (PD) for fire and missile detection, and high-performance high-electron mobility transistors (HEMT) for next generation microwave communication and power electronics Possible High Impact Journals forPublications Carbon ThinSolidFilms JournalofAppliedPhysics 103 Collaborators Prof. Dr. Zainuriah Hassan, Universiti Sains Malaysia (USM), PulauPinang,Malaysia. Prof. Dr. Kamarulazizi Ibrahim, Universiti Sains Malaysia (USM), PulauPinang,Malaysia. Prof. Dr. Takashi Egawa, Nagoya Institute of Technology, Nagoya, Japan. Prof. Dr. Takeo Furukawa, Tokyo University of Science, Tokyo, Japan. Prof. Dr. Masahiro Funahashi, Faculty of Engineering, Kagawa University,Japan. AppliedPhysicsLetter MaterialsLetter ChemicalEngineeringJournal Project No: UM.C/625/1/HIR/MOHE/SC/07 Title: An Empirical Kinetic Approach to Study the Occurence of Ion Exchange at the Aqueous Cationic Micellar Surface Principal Investigator : Professor Dr. Mohammad Niyaz Khan Faculty : Department of Chemistry, Faculty of Science SummaryofResearchProposal Theoccurenceofionexchangebetweencounterionsationicmicellarsurface wasprobablyfirstdetectedbykineticstudy.Nowitseemscertainthatthis is an ubiquitous feature of such a colloidal system. But the fine-detailed mechanism(s) of the occurence of ion exchange at ionic micellar surface remained essentially a major problem in various areas of interest. The ion exchangeconstant(alsoknownasionselectivityconstant)forionexchange ationicmicellarsurfacecanbedeterminedbyvariousphysicalandchemical techniques. Viscoelasticity in dilute surfactant solutions has been of great interest. It is believed that these viscoelastic systems form abnormally long (of several hundred angstroms) cylindrical micelles which are responsible for viscoelasticity.Itisoftenstatedintheliteraturethattheexistenceofthreadlike micellesisnecessaryforsurfactantstobedrag-reducersinturbulentflow.In spiteofdetailedstudies,severalaspectsoftheoriginofviscoelasticityhave remainedunanswered.Forexample,itisnotclearwhythecylindricalmicelles growtoseveralhundredangstromlengtheventhoughthevolumefrictionof thesurfactantsisstilloftheorderof10-3(atthemilimolarconcentrations). HIR Annual report 2011.indb 103 24/05/2012 9:44:55 104 High Impact Research Annual Report 2011 Objectives Methodology Todeveloptheanalyticalmethod(s) for the determination of rate law for cationic micelle-catalyzed reactions. To study the ion exchange at ionic micellar surface by the use of kinetics requires reaction rate study involving an appropriate semi ionic reaction carried out in the presence of ionic micelles. The main requirement of the reactionsystemisthattherateof the reaction must be significantly sensitive to the occurrence of ion exchange.Thereactionsweintend toselectforthisprojectare(i)pHindependent hydrolysis of anionic estersorimides,(ii)pH-dependent hydrolysis of non-ionic esters or imides and (iii) aminolysis of anionicestersorimides To investigate the kinetics and mechanism of cationic micellecatalyzedreactionsofinterest. To obtain/determine the ion exchange constants (KXBr) for ion exchange processes occuring at thecationicmicellarsurface. To establish a quantitative correlation between the values of KXBr(fordifferentX)andX–induced cationicmicellarstructuralgrowth Theratestudiesofthesereactions can more accurately and convenientlybestudiedbytheuse of UV-Visible spectrophotometric technique if there is a significant change in UV-visible spectra of the reactants and products. The rate of reaction was studied spectrophotometrically by monitoring either the decrease or increase in the absorbance at an appropriate wavelength as a functionofreactiontime For slow reactions (with half-lives of 45-90 minutes), four to six kinetic runs can be carried out simultaneously by the use of the multi sample cell programmer unit of the spectrophotometer The pH and cmc (critical micelle concentration) measurements can be carried out by the use of the appropriate instruments available inourresearchlabordepartment The observed data (absorbance versus reaction time) can be analyzedusingappropriatekinetic equation and nonlinear/linear least-squarestechnique Outcome Better understanding of the relationship between counterion ion affinity to micelle and counterion – induced micellar growth Possible High Impact Journals forPublications Langmuir Current Opinion in Colloid and InterfaceScience Advances in Colloid and Interface Science Journal of Physical Chemistry A andB Softmatter Collaborators Nil Project No: UM.C/625/1/HIR/MOHE/SC/08 Title: Mechanism of Binding of Antimicrobial Peptides on Targeted Bacterial Membrane Principal Investigator : Associate Professor Dr. Koshy Philip Faculty : Institute of Biological Sciences, Faculty of Science SummaryofResearchProposal Antimicrobial peptides (AMPs) are proteins of small molecular weight and canactagainstbacteria,viruses,fungiandcancercelllinesactingasnovel therapeuticproducts.ThelargerAMPsmayhavemorethan100aminoacids andoftenbringaboutlysisintargetcells.Thesmallerpeptidesfunctionby disruptingthestructureofcellmembranesinthetargetcells.Thesepeptides areofdiverseoriginexhibitingsimilarordifferentmodesofaction. Antimicrobial peptide mediated cell death show that some peptides may be able to kill cells within 2 to 3 minutes of exposure. Novel antimicrobial peptidesmayhavetheanswertodevelopmentofanewlineofantimicrobials inviewoftheincreasingantibioticresistanceandemergenceofsuperbugs worldwide. This study examines the mode of action of naturally occurring HIR Annual report 2011.indb 104 24/05/2012 9:44:56 High Impact Research Annual Report 2011 105 andsynthesizedpeptidesonselectedmicroorganisms,cancercelllinesand red blood cells as targets for growth inhibition and proliferation. With the elucidation of the fundamental mechanism, novel peptides can be isolated anddevelopedforpossibleusedasbiopharmaceuticals. Objectives Methodology The physical and chemical characteristics of synthesized antimicrobial peptides will be examined and compared with those bio-prospected from plant andmicrobialsources Test bacteria are selected for studying the effects of the antimicrobial peptides including strains from Escherichia coli, Helicobacter pylori, Staphylococcus aureus and oral bacteria isolated from Malaysian subjects. The peptide inhibition of the test bacteria are examined using standard microbiological methods. Hemolytic activities of the peptides are evaluated using erythrocyte cells by determining spectrophotometrically the amount of haemoglobin (Hb) released from 8% suspension of fresh rabbit red blood cells (RBCs).The variation in effect of the peptides on cell morphology will be examined by scanning electron microscopy. Circular dichroism (CD) experiments will be performed using a spectropolarimeter to determine the CD spectra of the peptides. To investigate the conformational changes induced by membranemimetic environments, dodecylphosphocholine and SDS micellesofdefinedcompositionwill beaddedtothepeptides.Foreach spectrum,thedatafromfivescans willbeaveraged.NMRexperiments are conducted to investigate the intramolecular hydrogen bondinginthepeptidesandNMR spectroscopy is used to generate useful information about the interaction between the peptides and micelles. Inflammation study will be carried out using appropriate in vitro cell lines and variationsingeneexpressionsare to be evaluated suing specially designedmicroarraygenechips The interactions between the peptides and the plasma membrane (bacterial membrane and erythrocyte cells) will be determined using NMR spectroscopy Themodeofactionofthepeptides in disrupting the membranes and the morphology of the targeted bacteriaandredbloodcellswillbe investigated Microarray genetic technique will be used to evaluate change in gene expression of inflammatory molecules by the action of the peptidesin vitro Outcome A better understanding of the fundamental mechanism of inhibition of microbial cells and regression of cancer cell lines by selected peptides can be generated and the results can be published in high impact tier one journals With the increase in antibiotic resistance from mutant microorganisms, the study will be able to throw new light on the use of novel antimicrobial peptides to control and manage the outbreaks of such pathogenic microorganisms Possible High Impact Journals forPublications JournalofClinicalMicrobiology PLOSBiology PLOSOne JournalofBacteriology JournalofBiotechnology NewEnglandJournalofMedicine AdvanceMicrobialPhysiology CellMicrobiology International Journal AntimicrobialAgents of Collaborators Professor Dr John Tagg, Microbiology Department, UniversityofOtago,Dunedin,New Zealand Dr. Osama Abou Zied, Sultan QaboosUniversity,Oman Professor Dr Andres Metspalu, University of Tartu & Head of EsoniaGenomeProject,Estonia Professor Sekaran Muniandy, UniversityofMalaya,Malaysia Dr. Noni Ajam, Deputy Head, UniversityofMalaya,Malaysia Dr. Kumaresan Nallasamy, UniversityofMalaya,KualLumpur, Malaysia HIR Annual report 2011.indb 105 24/05/2012 9:44:56 106 High Impact Research Annual Report 2011 Project No: UM.C/625/1/HIR/MOHE/SC/09 Title: Bioactive Compounds from Malaysian Plants Principal Investigator : Professor Datuk Dr. A.Hamid A.Hadi Faculty : Department of Chemistry, Faculty of Science SummaryofResearchProposal This research involves the extraction and isolation of phytochemicals from plantspecies.Thecrudeandpurecompoundswillsubjecttothebiological activityassay.Theactivitymechanismwillalsobestudied.Thisprojectalso involvesthesynthesisofbioactivemolecules.Thesynthesizedmoleculewill betestedfortheirbioactivity. Objectives Methodology To extract the natural compounds fromplantspecies Extraction of dried plant species using various solvent systems suchashexane,dichloromethane, andmethanol Toisolatethepurephytochemicals fromthecrudeextracts Torunbioactivityforthecrudeand purecompounds To synthesis molecules the bioactive To develop the compoundsfordrug bioactive Possible High Impact Journals forPublications Interesting results havebeen obtainedfromthisprojectandthis resultscanbepublished Isolationofpurecompoundsusing chromatographic techniques such as column chromatography, thin layerchromatographyandHPLC In tier-1 journal such as Journal of Natural Products, Tetrahedron letters,PlosandPhytochemistry. Test for bioactivity of pure compounds using standard protocol such as antioxidant, antiinflammatory,vasorelaxantand anticancer Collaborators Professor David Mc Nicol, GlassgowUniversity,Scotland Outcome Two papers have been published inFitotrapiaandMolecules Two papers have been submitted intier-1journal Morepapersareinpreparationfor publicationintier-1journal Project No: UM.C/625/1/HIR/MOHE/SC/11 Title: Understanding Guerbet Glycosides’ Self-Assembly Structures & Dynamics for Functional Nano-Biotechnology Principal Investigator : Professor Dr. Rauzah Hashim. Faculty : Department of Chemistry, Faculty of Science SummaryofResearchProposal Glycolipids can be found extensively in cell membranes of prokaryotes and eukaryotes. Their detailed chemical structure is functional to stabilize membrane structure and assist in molecular-recognition at the cell-surface. Glycolipidsareamphiphilescomprisingofasugarheadgroupandanalkyl chain.Theyareamphitropicabletoself-assemblewhendryaswellaswhen solvated and their role in the membrane processes is understood through theirlyotropicandsurfactantproperties.Thecellmembraneisassumedto be a fluid bilayer containing both a hydrophilic and a hydrophobic region. The former is involved in electrostatic interactions, mainly through the extensivenetworkofhydrogen-bondingfromtheheadgroup-headgroupand headgroup-water interactions, whereas the latter is governed by repulsive, steric interaction between the alkyl chains, which are dynamic and often HIR Annual report 2011.indb 106 24/05/2012 9:44:56 High Impact Research Annual Report 2011 107 assumed to be randomly organised giving its fluidity nature. Within this complexself-organisedmembraneassembly,thestructuralroleofglycolipids canbestbeunderstoodthroughasystematicexaminationofthesemolecules varying in headgroup geometry and their hydrocarbon chains structures, in absence of solvent (thermotropic) as well as with studies performed as a functionofwatercontent(lyotropic). Relative to the lyotropic, study on glycolipid thermotropic phase behaviour is recent less-well understood and investigation of possible thermotropic application is underexploited. For example, despite being chiral and ferroelectric possible tilted self-assembly structure similar to a tilted thermotropic smectic C or SC, in the glycolipid organization has not been shownuntilrecentlyeventhoughferroelectricphenomenaincellmembrane functions have been reported. In addition, temperature dependent current impliesthepresenceofpyroelectriceffectsandtheswellingofmembranes inresponsetoanappliedvoltagealsosuggeststhepresenceofpiezoelectric contributioninglycolipidbilayers.Thepresentresearchfocusonnature-like syntheticglycosidesderivedfromthefamilyofGuerbetalcohols. Objectives Methodology The objectives in this research are to understand the detailed structure of Guerbet glycosides using and to determine the possible polymorphism which may arise from heating these material.Dynamicsbehaviorinthe lyotropic will also be determined. The possible applications of these materials will be explored especiallyforpyroelectricbehavior Thepresentprojectfocusesonthe following: preparation of Gerbet glycosides. The self-assembly structures of these materials are studied by diffraction and scatteringtechniques(eg.SWAXS, SANS and synchrotron). Some basic dynamics of self-assembly will be determined by using deuteriumNMRandtime-resolved fluorescence spectroscopy. Aspects of modeling and simulation will be included to get detailed structure property relationship Nanoelectronic property of selfassemblyandinvestigationonthe effectofexternalperturbation(eg. field effect) on self-assembly will beattempted Outcome Possible High Impact Journals forPublications JournalofPhysicalChemistryB& C ColloidandSurfacesB ChemistryandPhysicsofLipids MaterialsChemistryandPhysics Langmuir, Nanomedicines LiquidCrystals CarbohydrateChemistry Collaborators: Prof.J.M.Seddon Prof.C.Solans Prof.G.R.Luckhurst Prof.OsamaK.Abou-Zied Producing novel materials for improvedformulation HIR Annual report 2011.indb 107 24/05/2012 9:44:56 108 High Impact Research Annual Report 2011 Project No: UM.C/625/1/HIR/MOHE/SC/12 Title: Nanocavities for Fuel Storage Principal Investigator : Professor Dr. Edward R.T. Tiekink Faculty : Department of Chemistry, Faculty of Science SummaryofResearchProposal Exploitingfunctionalizedphosphineandthiocarbamideligands,byincluding hydrogen-bondingfunctionality,and/orhavingphosphineandthiocarbamide molecules capable of interacting with more than one gold atom, will lead to a diverse variety of high-nuclearity clusters and supramolecular architectures.Thesewillbeexaminedfortheirluminescencecharacteristics and correlated with the formation of aurophilic interactions. The gold-rich species, representing a link between mononuclear species and nano-sized gold, and having water-solubilising groups, will be evaluated for their antitumouractivityaswellastheirpotentialuseahanstrheumatoidarthritisand other disease. The ability of the newly synthesized molecules, all-organic aswellasthegoldcompounds,toformco-crystalswillbeevaluated.This project will generate new supramolecular chemistry, luminescent materials, andindicationsforpharmacologicalpotential. Objectives Methodology The objectives of this research are multi-faceted and will have significant ramifications for supramolecular chemistry as well as metal-based drugs, and are summarised as i) to develop a design principle for the construction of high-nuclearity aggregated based on covalent, aurophilic and hydrogen-bonding interactions, ii) to fine-tune supramolecular architecture to control solid-state luminescence response,iii)tocorrelateaurophilic interactions with solution and solid-state luminescence, iv) to generate (more) water-soluble gold-rich species for biological activity, v) to explore topochemical photodimerization reactions mediated by aurophilic interactions, vi) to understand heterosynthon stability in the solid-state as revealed in cocrystals, and, finally, vii) to develop a hierarchy of supramolecular synthons Using principles of chemistry and a full range of physiochemical characterisation techniques, this project will be conducted on the following set of principles: i) to develop a design principle for the construction of high-nuclearity aggregated based on covalent, aurophilic and hydrogen-bonding interactions, ii) to fine-tune supramolecular architecture to control solid-state luminescence response,iii)tocorrelateaurophilic interactions with solution and solid-state luminescence, iv) to generate (more) water-soluble gold-rich species for biological activity, v) to explore topochemical photodimerization reactions mediated by aurophilic interactions, and vi) to provide a handbook outlining the hierarchy of supramolecular synthons HIR Annual report 2011.indb 108 functional groups for evaluation of pharmacological potential, and iv) to determine the propensity of thioamide and related molecules to form co-crystals with GRAS (Generally Regarded As Acceptable) as well as functionalizedorganicmolecules Possible High Impact Journals forPublications ChemicalCommunications CrystEngComm CrystalGrowth&Design DaltonTransactions InorganicChemistry Collaborators Prof.DrIonelHaiduc,Universitatea Babes-Bolyai Outcomes Prof. Dr Jan Reedijk, Universiteit Leiden The specific outcomes of this researchprogrammeareexpected to be i) the rational design of phosphinegold(I) thiocarbamate species of specific dimensions (0-, 1-, 2- and 3-D) employing a combinationofcovalent,aurophilic andhydrogenbondinginteractions, ii)thecorrelationofsupramolecular architectures with solid-state luminescence responses, iii) the generationofnovelhigh-nuclearity clusters with water-solubilising Prof.DrVivianWing-WahYam,The UniversityofHongKong Prof. Dr Michael J. Zaworokto, UniversityofSouthFlorida Prof. Dr Julio ZukermanSchpector, Universidade Federal deSãoCarlos 24/05/2012 9:44:56 High Impact Research Annual Report 2011 109 RESEARCH PROPOSAL (HIR-MoHE5Years) FacultyofDentistry Project No: UM.C/625/1/HIR/MOHE/DEN/01 Title: Dental Derived Stem Cells for Regenerative Therapies Principal Investigator : Associate Professor Dr. Hayaty Abu Kasim Faculty : Department of Conservative Dentistry, Faculty of Dentistry SummaryofResearchProposal The transplantation of human dental pulp stem/stromal cells (DPSCs) in humanmandiblebonehascreatedanothersignificantimpactinthefieldof regenerativemedicine.Thismadeforthefirsttimedentalstemcellresearch tomovefrombenchtobedside.HumanDPSCsareoriginatedfromneuralcrestlineageandcanbeobtainednon-invasivelyfromteeththatareextracted forclinicalreasonsandusuallydiscardedasbiologicalwaste.Studieshave shownthatDPSCsarecapableofdifferentiatingintofullyfunctionalneuronal cells, odontoblast, endothelium, hepatocytes and pancreatic cells. They have also shown some remarkable outcome in pre-clinical studies. This paradigm shift opens avenue into treatments for debilitating diseases with tailor-madechoiceofstemcellinanticipationtoachievemaximumefficacy in regenerative medicine. However, just like any other mesenchymal stem cells(MSCs)sourcestheuseofDPSCsintransplantationrequireslargescale expansionofcellsinordertocaterfortheneedofclinicalquantity.Inmost clinical trials, including the first human DPSCs transplantation, fetal bovine serum(FBS)hasbeenusedasthemainnutritionalsupplement.However,the useofxenogenicserumiscomplicatedbecauseofhighlot-tolotvariability coupledwiththeriskoftransmittinginfectiousagentsandimmunizingeffects. Thereforethereisalwaysaneedtosearchforalternativesourcestoreplace FBS wherein these substitutes must show competitive results. Human ES cells allow scientists to explore early human development through in vitro differentiation,whichrecapitulatesaspectsofnormalgastrulationandtissue formation.Arobustmethodforestablishingimmortalculturesofpluripotent stemcellsfromdiseasedindividualswouldnotonlybolsterdiseaseresearch butalsolayafoundationforproducingautologouscelltherapiesthatwould evade immune rejection and enable correction of gene defects prior to tissuereconstitution.Onestrategyforproducingautologous,patient-derived pluripotent stem cells is somatic cell nuclear transfer (SCNT). In a proof of principleexperiment,SCNT-embryonicstem(ES)cellsgeneratedfrommice withgeneticimmunodeficiencywereusedtocombinegeneandcelltherapyto repairthegeneticdefect.However,todate,SCNThasnotprovensuccessful inthehumanand,giventhepaucityofhumanoocytes,isdestinedtohave restrictedutility.Theseresultsserveasproof-of-principlethatpluripotentstem cellscanbegeneratedfromsomaticcellsbythecombinationofappropriate factors.Furthermore,thisgroupsuccessfullygeneratediPScellsbyretroviral transductionfromhumandermalfibroblastsandothersomaticcells,which arecomparabletohumanEScellsintheirdifferentiationpotentialin vitroand in teratomas. Given the robustness of the strategy, direct reprogramming appearstobeasimplisticsourceofpatient-derivedcelllines.Suchlineswould be instantaneously valuable for medical research, yet current methods for reprogrammingrequireinfectingthesomaticcellswithmultipleviralvectors, therebyprecludingconsiderationoftheiruseintransplantationmedicineat thistime.Thereforethefollowingprojectswillbeconductedtoaddressthe3 mainissues-:theusageofanimalproductindentalstemcellculturing,large scale expansion to cater the clinical scale manufacturing and induction of pluripotentstemcellsfromdentalstemcells. HIR Annual report 2011.indb 109 24/05/2012 9:44:56 110 High Impact Research Annual Report 2011 Objectives Methodology Programme1:Isolation,expansion, characterization and multilineage differentiation of dental stem cells inxeno-freeculturecondition TheInstitutionalEthicsCommittee will approve sample collection protocols used. The inform consent will be obtained from all human subjects that will participate in the study and the nature of the procedure and possiblediscomfortsandriskswill be fully explained. The following experiments will be conducted to achieve the aforementioned objectives, isolation of stem cells from various sources of dental tissues as well as from other sources,colonyformingunits,cell proliferationassay,flow-cytometry, immunocytochemistry, RT-PCR, Real Time PCR, Microarray, karyotyping, immunohistochemistry,safetyandtoxicitytest. 1. To optimize the isolation of dental stem cells in a xenofree culture condition for therapeuticusage 2. To identify the level of expansion of dental stem cells in a xeno-free culture condition 3. To determine whether dental stemcellsculturedinaxenofreecultureconditionareable to differentiate into neuroectcoderm, mesoderm and endodermlineages Programme 2: large scale expansion of dental pulp stem cellsfortherapeuticpurposes 1. To design a large scale cell expansionsystemusingstem cells from single and pooled donors 2. To compare the biosimilarities of dental stem cells derived from single and pooleddonorsinalargescale system 3. To compare the large scale stem cells from dental pulp withothercelllines Outcome Optimisationand expansion of dentalderivedstemcellsinxenofreeculturecondition Better understanding of advantages and disadvantages of dental derived stem cells expanded from single and pooled donors Derivation of iPS cell lines from dentalorigin Understanding the potential of dental derived stem cells in regenerativemedicine Possible High Impact Journals for Publications JournalforDentalResearch JournalofEndodontics JournalforPeriodontalResearch StemCellsResearch RegenerativeMedicine Collaborator Prof. Jeremy Mao, Tissue Engineering & Regenerative MedicineLaboratory, College of Dental Medicine, ColombiaUniversity,USA Hygieia Innovation Sdn. Bhd, Federal Territory of Putrajaya, Malaysia. Programme 3: Derivation of induced Pluripotent Stem Cells (iPScelllines)fromdentalorigin 1. Tounderstandtheunderlying biologyofreprogramingcells through viral and non-viral induction 2. To identify the efficacy of dental pulp stem cells in developing towards induced pluripotent cell lines (iPS cell lines) 3. To differentiate the induced pluripotent stem cells from dental origin into lineage progenitorcelllines HIR Annual report 2011.indb 110 24/05/2012 9:44:56 High Impact Research Annual Report 2011 111 Project No: UM.C/625/1/HIR/MOHE/DEN/02 Title: Pre-Clinical Assessment of Autologous/Allogeneic Mesenchymal Stem Cells Fromvarious Sources Principal Investigator : Associate Professor Dr. Sabri bin Musa Faculty : Department of Children’s Dentistry and Orthodontics, Faculty of Dentistry SummaryofResearchProposal Mesenchymal stem cells are multipotent stromal cells that can differentiate intovariouslineagesandareknowntobehypo-immunogenicinnature.These uniquepropertieshaveattractedtheattentionofcellbiologists,immunologists as well as clinicians leading to initiation of pilot clinical trials for various indications. However, MSC transplantation in humans has its own benefits and risks. The presence of MHC-I and up-regulation of MHC-II expression in the presence of host interferon-gamma are important determinants of their use as immunomodulators. Safety profiling in terms of cytogenetic instability, support of tumor growth, ectopic differentiation, fetal calf serum response, effect of inflammatory molecules released from MSCs, and cell productpurificationmustbecarefullyconsideredpriortoincorporatinginto clinicalpractice,speciallyforallogeneicMSCtransplantation.Mesenchymal stemcellshavealargenumberofreceptorsthatcanmakethemintolerant ofT-cellsandactivatetheMHC-IIup-regulation.Autologous/allogeneicMSC transplantationoftenfollowsacascadeofimmunefunctionmodulationevents resultingincomplexcell–cellinteractionsandvaryingresponsestodifferent cell types. On most occasions autologous cells may not pose as serious a threatofrejection,graftversushostdisease(GvHD)orimmunedeviationas allogeneicMSCtransplantation.ThecontrastingreportsoftheMSCimmune modulation and subversion of the same on the host milieu or under other inflammatoryconditionstriggeringthereversalofthesamefunctionsindicate that these cells must be thoroughly evaluated for the cell–cell compatible factors . Further, MSC passage cell infusion number, frequency, duration, concurrent immune-suppression and pre-injection manipulation of MSCs areneededtoderiveoptimaltherapeuticbenefitfromMSCtransplantation. Withthegapsinexistingliterature,wefelttheneedtoexplorethefeasibility of developing a pre-clinical model for a few common diseases using mesenchymalstemcellsderivedfromvarioussources. Objectives The objective of the project has beendividedinto3majorsegments in order to fully understand the biologyimportanceofdentalstem cellsinregenerativetherapies 1. Theefficacyofmesenchymal stem cells in critical limb ischemiapre-clinicalmodel Theobjectivesare: a) b) c) HIR Annual report 2011.indb 111 To set up and possibly validate the methods to investigate biodistribution, trafficking and persistence of mesenchymal stem cells isolated from various sources in vivo, tumorigenic potential andlocaltolerability Tosetupanappropriate animalmodelforcritical limbischemia Toexamineprosandcons of immunocompromised animalsandhomologous models in the aforementioneddisease models in the aforementioneddisease 2. The effect of mesenchymal stem cells transplantation in an Osteoarthritis (OA) preclinicalmodel. Theobjectivesare: a) b) c) To set up and possibly validate the methods to investigate biodistribution, trafficking and persistence of mesenchymal stem cells isolated from various sources in vivo, tumorigenic potential and local tolerability in anOAmodel Tosetupanappropriate animal model for osteoarthritis(OA) Toexamineprosandcons of immunocompromised animalsandhomologous 3. Thepotentialofmesenchymal stem cells transplantation in a cerebral stroke pre-clinical model. Theobjectivesare: a) b) c) To set up and possible validate the methods to investigate biodistribution, trafficking and persistence of mesenchymal stem cells isolated from various sources in vivo, tumorigenic potential and local tolerability in ancerebralstrokemodel Tosetupanappropriate animal model for cerebralstroke Toexamineprosandcons of immunocompromised animalsandhomologous models in the aforementioneddisease 24/05/2012 9:44:56 112 High Impact Research Annual Report 2011 Methodology TheInstitutionalEthicsCommittee will approve sample collection protocols used. The inform consent will be obtained from all human subjects that will participate in the study and the nature of the procedure and possiblediscomfortsandriskswill be fully explained. The following experiments will be conducted to achieve the aforementioned objectives, isolation of stem cells from various sources of dental tissues as well as from other sources,colonyformingunits,cell proliferationassay,flow-cytometry, immunocytochemistry, RT-PCR, Real Time PCR, Microarray, karyotyping, immunohistochemistry,safetyandtoxicitytest Outcome 1ISIPublicationsfortheYear2011 Possible High Impact Journals forPublications StemCells PNAS PLoSone JournalofDentalResearch Collaborator Hygieia Innovation Sdn. Bhd, Federal Territory of Putrajaya, Malaysia. Project No: UM.C/625/1/HIR/MOHE/DEN/03 Title: Constructing the Cancer Progression Model: The Identification of Key Players in Malignant Transformation Principal Investigator : Professor Dr. Zainal Ariff Abdul Rahman Faculty : Department of Oral and Maxillofacial Surgery, Faculty of Dentistry SummaryofResearchProposal It is well-established that cancer occurs as a result of a sequential accumulation of genetic alterations. The ability to identify the specific changes between normalcy and malignancy enables us to understand the geneticchangesthatareneededformalignanttransformation.Often,cancer ispreceededbypremalignantstageswhichallowsanopportunitytointervene topreventcancerdevelopment.Changesinthegeneticprofilesofthedifferent carcinogenesisstages,atboththeepithelialandstromacompartmentswill provide an opportunity to use this information as a screening tool to catch theselesionsearlybeforetheyreachmalignancy.Oralcancer(oralsquamous cellcarcinoma;OSCC)isasignificantdiseaseworldwideandaccountsforup to400,000newcaseseachyear.Usingoralcancerasamodel,weproposeto analysethegeneticchangesthatdrivemalignanttransformation. Objectives Using array-based methods and systembiology,wehopetoidentify genetic changes that drive the malignanttransformationprocess, and to use this information to develop gene signatures for diagnostic and prognostic purposes. Further, we aim to establish in vitro models to study the function of genes that will be identifiedinthisstudy Methodology Formalin-fixed paraffin-embedded tissue specimens for this project will be obtained from the Oral Cancer Research and Co- HIR Annual report 2011.indb 112 ordinating Centre, Universiti Malaya.Theepithelialandstromal tissues of the specimens will be microdissected. RNA will be extractedandarray-basedstudies will be performed. A systems biology approach will be used to analyse the gene expression and DNA array results. Dysplastic cell lineswillbeestablishedfromfresh tissuestodevelopin vitromodels. Upto3over-expressedgeneswith maximum biological significance derived from the array-based studies will be selected and studiedusingthein vitrosystems. Thesestudieswillformthebasisof inhibitingtheproteinexpressionof candidategeneswiththepurpose of curbing the development of OSCC Outcome From the studies, we will be able to identify genetic markers which drive malignant transformation. Based on the genetic changes, a screening tool to catch these lesions early before they reach malignancycanbedeveloped. Possible High Impact Journals forPublications ClinicalCancerResearch CancerResearch JournalofPathology Oncogene BritishJournalofCancer 24/05/2012 9:44:56 High Impact Research Annual Report 2011 Collaborators ProfDrRosnahBintiZain,PnWan Nabillah Abd Ghani. Oral Cancer Research and Coordinating Centre,UM. Dr Lau Shin Hin, Institute for MedicalResearch,Malaysia Dr Wan Mahadzir Wan Mustafa, Dr Mannil Thomas Abraham, Dr Norlida Abdullah, Ministry of HealthMalaysia 113 Prof Dr Stephen Prime, Dr. Nicola Cirillo,UniversityofBristol,United Kingdom Asst Prof Dr Tan Aik Choon, University of Colorado, United States Statistical Analysis Laboratory, Dept. of Clinical Research, KaohsiungMedicalUniversity Assoc Prof Dr Connie Yang Yi-Hsin, Chung-Ho Memorial Hospital,Kaohsiung,Taiwan Dr Thomas George, Faculty of Dentistry,UM Project No: UM.C/625/1/HIR/MOHE/DEN/04 Title: Periodontal Disease: The Development of Genomic Biomarkers and the Impact of Disease on Quality of Life Principal Investigator : Dr. Rathna Devi Vaithilingam Faculty : Department of Oral Pathology and Oral Medicine and Periodontology, Faculty of Dentistry SummaryofResearchProposal Periodontal disease, a chronic inflammatory disease which results in irreversible attachment loss, bone destruction and tooth loss, is a major oralhealthproblemaffecting90.2%ofMalaysianpopulation.5.5%ofthese subjects have advanced periodontal disease. Although periodontitis is a multi-factorial disease and microbial and environmental factors initiate and modify disease progression, findings from several studies suggest that the severity and progression of periodontitis might be associated with genetic polymorphisms.Geneticallytransmittedtraitssuchasgenepolymorphisms may accentuate the host’s inflammatory response to a bacterial challenge andaccountforvariationinindividualsusceptibilitytoperiodontitis.Here,we proposetoidentifycandidategenesandpolymorphismsthatareassociated with periodontitis using genomewide association studies (GWAS). The analysis and identification of potential genes of this scale (using GWAS) is unprecedented in South East Asia and current literature indicates that the existing studies conducted in the West may not directly be relevant to the Asianpopulationduetoinherentgeneticdifferences.Apreliminarystudyto establishthebaselineSNPsinvolvedinadvancedperiodontaldiseasewillbe expandedfurthertoincludesubjectsbothwithinMalaysiaandintheSouth EastAsiancountriesthroughexistingcollaborationstovalidatetheSNPsthat wereidentified. Objectives To validate if known genetic polymorphisms for periodontal disease express functional evidenceinMalaysianperiodontitis subjects by assessing host responseexpression To analyse and identify genetic susceptible loci of advanced periodontaldiseaseusingGWAS Tovalidateifknownpolymorphisms for periodontal disease are associated with risk factors like microbiological parameters, ethnicityandsystemicdiseases Ingeneral,theoverallmethodology ofthiscase-controlstudy,centres around the identification of advanced chronic periodontitis patients who have not undergone treatment and patients without periodontal disease acting as controls. Control patients will be To evaluate the oral health related quality of life impacts of periodontalpatients HIR Annual report 2011.indb 113 Methodology matched on sex, age (within five years)andethnicity Data collection will include demographicdata,lifestylehabits, levelofeducation,dentalvisitsand brushing frequency. The patients will then be examined and their clinical parameters (excluding the 8’s) will be assessed using PlaqueIndex(Silness&Loe,1964), Gingival index (Loe & Silness, 1963), Bleeding Index, Clinical attachment loss and Probing PocketDepth 24/05/2012 9:44:56 114 High Impact Research Annual Report 2011 Patients’heightandweight(forBMI calculation) will also be recorded. Bloodandplaquesampleswillbe collectedfromthesepatients Host response expression of known genetic polymorphisms for cytokines (ILs, TNF, TGF), receptor polymorphisms and other polymorphisms will be evaluated from serum samples using ELISA. Microbiological identification and quantification of Porphyromonas gingivalis, Tannarella forsythia, Prevotella intermedia and Aggregatibacter actinomycetemcomitans will be conducted using Real Time-PCR. The OHIP-14 questionnaire (Oral Health related Quality of Life survey) which has been validated for the Malaysian population will be used to assess the oral health impacts of periodontal disease on these patients. GenotypingandClinicalChemistry will be conducted through GWAS, whereby sequencing of susceptibility loci in selected genes and fine-mapping of the association signals of selected geneswillbeconducted Outcome Better understanding of genes that predispose individuals to periodontitis Individualswhocouldbenefitfrom early and appropriate periodontal treatmentcanbeidentifiedandthis may ultimately improve patients’ oralhealthrelatedqualityoflife Possible High Impact Journals forPublications JournalofClinicalPeriodontology JournalofPeriodontology HumanMolecularGenetics JournalofPeriodontalResearch JournalofDentalResearch Collaborators Prof Mark Bartold, University of Adelaide,Australia Project No: UM.C/625/1/HIR/MOHE/DEN/05 Title: Tissue-Engineered Oral Mucosa Principal Investigator : Associate Professor Dr. Chai Wen Lin Faculty : Department of General Practice and Oral and Maxillofacial, Faculty Dentistry SummaryofResearchProposal With the advance of tissue-engineering technology, innovative oral mucosa substituteshavebeendeveloped.Ithasbeenusedtocoverthedefectsinoral cavityafteroralandmaxillofacialsurgerysuchaspremalignantandcancerous excision,orpreprostheticsurgery.Besidesitsuseforintra-oraldefects,some studieshaveculturedoralmucosalequivalents(OMEs)forextra-oralgrafting, suchasfortissuesubstitutesinurethroplasty,extensiveburnwoundandeyelid reconstruction.InadditiontotheclinicalapplicationoftheOMEs,themodels havebeenusedinin-vitrostudies,suchaspermeabilitytestfortransmucosal drugdelivery,oralmucosalresponsetoinfection,biocompatibilitytestingfor dentalbiomaterials,andimplant-softtissueinterfaceinvestigations. HIR Annual report 2011.indb 114 24/05/2012 9:44:56 High Impact Research Annual Report 2011 Objectives Methodology Using cadaveric acellular dermis, weaimtodevelopa3-dimensional oral mucosa equivalent that will serve wide potential as in intraoral grafting, in-vitro models for the investigation of the implantsoft tissue interface. However, the instability of cultured keratinocytes lead us to explore the potential of dental pulp stem cell that will further direct us to investigate the interactions of various mesenchymal stem cells, i.e. gingival, periodontal ligament fibroblasts, pulpal stem cells, bone marrow stroma cells on the epithelial morphogenesis of oral mucosalequivalents To develop the oral mucosal model, four different cell sources, i.e.gingivalfibroblasts,periodontal ligament fibroblasts, pulpal stem cellsandbonemarrowstromacells will be used. These organotypic tissueswillbeculturedondifferent types of scaffolds and different duration to obtain an optimised epithelial morphogenesis. The engineered organotypic tissues willbecharacterizedhistologically andquantitativelyevaluatedusing a permeability test. Exploration of regenerationofperi-implanttissue willbeconductedusing periodontal fibroblasts which will be cocultured onto the pericardium membrane.Theproteinexpression oftheinteractionoftheregenerated tissue will be investigated. The investigation of peri-implant tissue will be conducted using in-vitro and in-vivo models. For in-vitro model, based on the developed oral mucosa model and new implant surfaces, the qualityofthebiologicalsealofthe implant-softtissueinterfacewillbe evaluated qualitatively as well as quantitatively.Asforin-vivostudy, the soft tissue response on the dentalimplantswillbeinvestigated inhumanandanimalsubjects 115 substitutes for grafting purposes. Theoralmucosaldonorsitecould be the most convenient site for cells harvesting in constructing the tissue substitutes. Hence, the knowledge of oral epithelialmesenchymal interaction will enhancethepotentialconstruction ofsofttissuesubstitutesforclinical applications.Inaddition,thethree dimensional tissue-engineered oral mucosal model is a more representative in-vitro model for various in-vitro studies such as biocompatibilitytestoforalhealth products, drug diffusion, invasion of infectious or cancerous lesions and implant-soft tissue interface investigations Possible High Impact Journals forPublications JournalofPeriodontology JournalofClinPeiodontol ClinicalOralImplantResearch ClinicalImplantDentalResearch JournalofDentalResearch Journal of Biomedical Materials Research DentalMaterials Collaborators Outcome A better understanding of the epithelial-mesenchymalinteraction inregulatingepithelialphenotypes during tissue-engineering, could advance the technology in constructing different tissue substitutes for either in-vivo or in-vitro purposes. To date, there is still a lack of ideal tissue HIR Annual report 2011.indb 115 Dr Keyvan Moharamzadeh, University of Sheffield, Sheffield, UK Dr Zurairah bt Berahim, USM, Kelantan 24/05/2012 9:44:56 116 High Impact Research Annual Report 2011 Project No: UM.C/625/1/HIR/MOHE/DEN/06 Title: Biobanking of Oral Cancers: An Assessment of Survival, Clinicopathological Parameters, Management Strategies, Nutrition, and Genetic Susceptibility of Patients Principal Investigator : Professor Dr. Rosnah Mohd Zain Faculty : Department of Oral Pathology and Oral Medicine and Periodontology, Faculty of Dentistry SummaryofResearchProposal Oral Cancer Research & Coordinating Centre (OCRCC), at the Faculty of Dentistry, Universiti Malaya (UM) through collaborations with Universiti Sains Malaysia (USM), Oral Health Division, Ministry of Health (MOH) and Cancer Research Initiatives Foundation (CARIF) has initiated a biobanking system named as the Malaysian Oral Cancer Database and Tissue Bank System(MOCDTBS)in2003undertheIRPARMK8fundingmechanism.The MOCDTBSisnowattherightplacetoprovidegoodclinicalandlaboratory dataasthedatacollectedisnowmaturedwhereithasreachedthe5-year markwhere5-yearsurvivaldatawouldbeavailable.Thusweneedtoevaluate thedifferentaspectsthatcontributetotheriskoforalcancerandthesurvival ofthepatients. Objectives Methodology In this study, we plan to assess relationship between clinicopathological parameters, managementstrategies,nutritional status and genetic susceptibility withriskoforalcancerandsurvival of these patients. Furthermore, duetotheincreaseintherequest for data with good follow up and biospecimensofhighqualityfrom bothresearchersandpostgraduate students, there is a need for the MOCDTBS to be consolidated and enhanced. The maintenance, consolidation and further development of the MOCDTBS will allow for continuous credible data and specimen collection thus providing for a large number of high quality biospecimen with good data for future research projects Data on various parameters such as sociodemography, clinicopathological parameters, details of patient management and nutrition; and specimens will be collected from three higher learning institutions and six government hospitals. Data and specimens collected will then be analysed To enhance MOCDTBS for better retrieval, a system where data from database and biospecimen information from the Freezerwork can be integrated for ease of retrieval will be developed. The currentdatabaseandFreezerwork software will also be upgraded to allow for a more efficient system of data/specimen storage and retrieval as there is an increase of more complex data such as intervalfollow-updata,histological sections and laboratory findings. Membership into ISBER, a leading international forum for promoting consistent, high quality standards, ethical principles and innovationinbiospecimenbanking will also be initiated to ensure that the MOCDTBS conforms to internationalstandards Outcome Establishment of a more comprehensive oral cancer data andspecimenbank. Clinicopathological parameters will be established for better HIR Annual report 2011.indb 116 prognostic evaluations of oral cancerpatients Identification of the best management strategies for oral cancerpatients Knowledge on the effect of nutritionintakeonriskandsurvival ofpatients. Identification of important genes susceptibletooralcancer Recognition of Universiti Malaya as the repository for oral cancer biospecimen collection and analysis Possible High Impact Journals forPublications OralOncology Head&Neck American Journal of Clinical Nutrittion HumanGenetic Cancer Epidemiology Biomarkers &Prevention EuropeanJournalofEpidemiology International Epidemiology Journal of Collaborators Oral Health Division, Ministry of Health UniversitiSainsMalaysia Cancer Research Foundation(CARIF) Initiatives 24/05/2012 9:44:56 High Impact Research Annual Report 2011 117 Project No: UM.C/625/1/HIR/MOHE/DEN/07 Title: The Oral Health Status, Unmet Needs, Barriers and Management Strategies for Dental Healthcare Among HIV/ AIDS and Other Patients With Special Needs in Malaysia Principal Investigator : Dr. Jacob John Faculty : Department of General Practice and Oral and Maxillofacial, Faculty of Dentistry SummaryofResearchProposal Withanestimated90000personswithHIV/AIDSinMalaysialivinglonger,the needforroutinedentalcare,aswellasrelieffromthediscomfortanddisability associated with concomitant oral lesions is increasing steadily. Changes in the mouth are common in a person with a weakened immune system and also while taking certain medications. However, the fear among healthcare providersofbeinginfectedhasledtoirrationalanddiscriminatorytreatment ofpeoplelivingwithHIV/AIDS.PeoplelivingwithHIVhavemoreunmetoral healthcareneedsthanthegeneralpopulationandtheyalsohavemoreunmet oral health care needs than unmet medical needs. Desired oral healthcare forpatientswithspecialneedscanonlyberenderedifnegativeperceptions amongthehealthcareprovidersareeliminated,accesstocareimprovedand innovativepreventiveprogramsdeveloped. Objectives Methodology Outcome To evaluate the oral health status in terms of prevalence of dental, periodontal, mucosal lesions and quality of saliva in relation to generalhealthamongthesubjects. The oral health status of HIV/ AIDS patients and other patients with special needs recruited for this study in terms of prevalence of dental, periodontal,mucosal lesionsandsalivaryqualitywillbe determined. The findings will then be correlated with their general health and perceived oral health related quality of life. The costing for managenment of the subjects willalsobedetermined Data on the oral health status of HIV/AIDS patients as well as patients with special needs in Malaysia To identify the oral healthcare rendered to the subjects and the treatmentneeds/barriersofthese patients To assess the perception and atitude of dental healthcare providers in managing oral health statusofthesubjects. To analyse the costing of delivery ofcareforthesubjects To recommend guidelines and policiestoimprovetheoralhealth status of HIV/aids patients and patients with special needs in Malaysia Dentalhealthcareproviderswillbe trainedtorecognizethetreatment needs and mangement strategies of these patients by conducting standardization training and calibration workshops. The knowledge on treating these patients will be assessed at training to get the baseline data on the level of awareness and experienceofthedentalhealthcare providers. The effectiveness of this standardization workshop on oral health management of these patientswillbeassessed Aninterventionprogramtoimprove the oral health status of this population will then be designed based on the data collected. This intervention program will be evaluated for its effectiveness and finally, recommendations on guidelines and policies on oral health treatment strategies in treating patients with special needsinMalaysiawillbemade HIR Annual report 2011.indb 117 New knowledge on the unmet needs, barriers as well as perception and attitude of dental health care providers on treating patients with special needs in Malaysia Training of dental healthcare providersforbetteroralhealthcare management of patients with specialneedsinMalaysia Possible High Impact Journals forPublications Community Dentistry & Oral Epidemiology JournalofPeriodontology Brazilian Journal of Infectious Diseases MedicalEducation AIDSPatientCareandSTDs Collaborators CentreofExcellenceforResearch inAIDS(CERiA) MinistryofHealth,Malaysia MalaysianPrisonsDepartment Dr. K. Ranganathan, Prof. of Oral & Maxillofacial Pathology and ResearchDirector,ChennaiDental ResearchFoundation DrRuthGray,InternationalLiaison Officer, National Association of PrisonDentistry,UK 24/05/2012 9:44:56 118 High Impact Research Annual Report 2011 Project No: UM.C/625/1/HIR/MOHE/DEN/10 Title: Identification of Cancer Specific Genomic Duplications and Deletions by Use of Array Based Comparative Genomic Hybridization (aCGH), Validation of Differentially Expressed Genes and Single Nucleotide Polymorphisms (SNPs) Studies and Protein Array Analysis: Possible Prognostic Tools Principal Investigator : Professor Dr. Rosnah Mohd Zain Faculty : Department of Oral Pathology and Oral Medicine and Periodontology, Faculty of Dentistry SummaryofResearchProposal Despite the progress in diagnosis and treatment of oral squamous cell carcinoma(OSCC),themortalityandmorbidityratesareexceptionallyhigh. Ofnote,oralcarcinogenesisisamultistepprocessinvolvingtheaccumulation of chromosomal aberrations which could lead to oncogenic transformation byactivationofanoncogeneandinactivationoftumorsuppressorgene.In viewofthis,thisstudyaimstoperformthearrayCGHandgeneexpression microarray with similar samples in order to identify the ‘driver’ gene which conferstogrowthadvantageinoralcarcinogenesis.Thecorrelationbetween chromosomal alterations regions (from aCGH) and gene expression data (microarray) with socio-demographic and clinico-pathological parameters can facilitate early intervention and identify key genetic abnormalities that reflect different stages of tumour progression (development, invasion and metastasis). Thisstudyalsocarriesoutproteinarraytoidentifythetumorauto-antibodies (TAAs) in oral cancer patients. TAAs could play roles as novel diagnostic cancerbiomarkersandmaycontributetowardsabetterunderstandingofthe molecularmechanismsinvolved. Objectives Theaimofthisprojectistoidentify copynumberalterations(CNAs)in oral cancer patients and correlate the CNAs with sociodemographic andclinic-pathologicalparameters. Using advanced bioinformatics approaches, the integration of CNAs and gene expression data will give a comprehensive picture of biomarkers that are highly correlated to oral cancer. This study also aims to determine the mRNA and protein expression for potential oncogenes and tumor suppressor. In order to determine the implication of the selected gene(s) in oral carcinogenesis, further downstream functional assays will be carried out. This studywillannotatenoveltranscript differentially expressed between oral cancers and normal samples from previous trancriptome sequencing Tumor auto-antibodies (TAA) will be determined using advanced proteinarrayusingserumsample. Identification of TAA could play roles as novel diagnostic cancer biomarkers and may contribute HIR Annual report 2011.indb 118 Methodology towards a better understanding of the molecular mechanisms involved. Based on previous studies, a few novel SNPs were identified.Asthesetumorspecific markerscouldbeusedtodevelopa diagnostictoolforearlydetection, this project aims to validate the known and novel SNPs/mutation discoveredinoralcancersamples gDNAandcDNAofOSCCsamples will be concurrently used for array CGH and gene expression microarray study. The matched potential oncogenes and tumor suppressor genes will be further studied using real time PCR and IHC technique. Their function in oral cancer will be characterized usingsiRNAknowdowntechnique inselectedoralcancercellline(s). The gene annotation process is conducted in three stages, which are nucleotide level annotation, protein-level annotation and process-level annotation. Through our collaborations with Oxford Gene Technology, we plan to determine the novel TAA from OSCC Indian patients using protein array. The novel TAA will then be further validated using ELISA/Westernblottechnique.The validationofthenovelandknown SNPs will be carried out using RFLPandsequencingmethod 24/05/2012 9:44:57 High Impact Research Annual Report 2011 Outcome Collaborators Identification of oral cancer markers and mutations (biomarkers) that can be linked to increased risk enabling preventive measurestobetakenatanearlier stage Oral Health Division, Ministry of Health 119 CARIF OxfordGeneTechnology,UK Possible High Impact Journals forPublications PlosOneBiology OralOncology JournalofProteomics Cancer Research Biology / Genome OralOncology Head&Neck InternationalJournalofCancer Pathology OralOncology CancerResearch/GenomeBiology HIR Annual report 2011.indb 119 24/05/2012 9:44:57 120 High Impact Research Annual Report 2011 RESEARCH PROPOSAL (HIR-MoHE5Years) FacultyofComputerScienceandInformationTechnology(FCSIT) Project No: UM.C/625/1/HIR/MOHE/FCSIT/03 Title: Mobile Cloud Computing: Device and Connectivity Principal Investigator : Associate Professor Dr. Abdullah Gani Faculty : Department of Computer System & Technology, FCSIT SummaryofResearchProposal Cloud computing (CC) is the future. As such, IBM, Amazon, HP and many more have invested in the infrastructure. Gartner Research estimates CC globalmarketvaluecouldreachUSD150billionin2014.Thepublicasuser has responded positively to the services offered by CC due to a bunch of advantages. However, those services can only be enjoyed by powerful devicessuchasdesktops,andlaptops.Smallportabledevicessuchassmart phones,tabletswiththelimitationinprocessingpower,storagecapacity,and batterylifeareunabletotaptheadvantagesrenderedbyCC.Thisresearch willfindwaystonarrowthegapbetweenCCandsmartphonesbycreatinga smartphone-friendlyarchitectureandoptimizethecapabilityofsmartphones tosuitthenatureofCC. Objectives Methodology The research focuses on developinganewmobileplatform and wireless connectivity architecture that can access the richcloudcomputingservicesfrom smartphone.Threemajorprojects areundertaken,asfollows: The research is undertaken by three groups. Each member of the project group works on specific project. Each project will work on the proposed model, generated through an intensive study on the literature of CC, Grid Computing and Distributed Systems to produce a model that lateronwouldbeusedtodevelop aprototype • Lightweight mobile architecture. The architecture of Rich Mobile Application (RMA) is proposed • Seamless wireless broadband connectivity. The architecture that supports heterogeneity is proposed • Security.Privacyisthemain concern in the community, and therefore this project addressestheissueofdata availability Prior to developing a prototype, the model will be validated by runningaseriesofsimulation.The prototype is used for the purpose ofevaluation Outcomes Possible High Impact Journals forPublications IEEE/ACM Networking Transaction on IEEETransonMobileComputing IEEE Trans on Parallel and DistributedSystems Future Generation Systems Computer Collaborators Nasser Abouzakhar, University of Hertfordshire,UK Raul Acquinor, Universidad de Colima,Mexico. Raj Kumar Buyya, University of Melbourne,Australia Newmodelofarchitectures Prototypes Simulationcodes AcademicReports HIR Annual report 2011.indb 120 24/05/2012 9:44:57 High Impact Research Annual Report 2011 121 Project No: UM.C/HIR/MOHE/FCSIT/04 Title: Recursive Approach for the Design of Asynchronous Sequential Circuits Principal Investigator : Mohammed Ziaur Rahman Faculty : Department of Computer System & Technology, FCSIT SummaryofResearchProposal The current processors are limited by the performance of their clock cycles. This is a fundamental disadvantage of synchronous circuits. As the developmentpushedthelimitstoworkfurtherincreasingtheprocessorspeed accordingtoMoore’slawwillnotbepossiblebysynchronoustechniques.An alternativeistodeviseasynchronousclock-lessprocessors.Inthisresearcha consolidatedapproachwillbetakentodeviseafullyfunctionalasynchronous clock-lessprocessortoovercomethechallengesofsynchronousprocessors. Objectives Methodology Outcome Design and improve mechanisms for efficient hand-shaking of asynchronousdigitallogiccircuits The existing simulation and electronic design automation (EDA) tools from Synopsis, Mentorgraphics or Orcad will be used.Additionally,astheproposed approach is fundamentally differentfromexistingsynchronous sequential circuits, newer tools need to be implemented and tested for the simulation and realizationofthenewercircuits New theories for asynchronous sequential circuits will be developed. The theoretical basis will be exploited to design fully asynchronous self-timed processors that will challenge the mainstreamcomputerprocessors Design new adder/multiplier logic circuits using recursive circuit invented and patented by the principal researcher. These building blocks will be utilized in thenextobjective To devise a complete prototype asynchronous reduced instruction set processor using self-timed recursivecircuit Development of design tools for asynchronous circuit simulation that will particularly address simulationofrecursivecircuits Developmentofproperinstruction set for the new processor and assembly language compiler for thedesignedinstructionset Three major groups will be operating for the realization of the project. Firstly, the theoretical evaluation team will delve deep into the fundamental aspects of asynchronous processors. Secondly, the system evaluation and simulation team will be involved for design of software solutionsforthepropersimulation of asynchronous systems. Lastly the physical verification team will be involved for VLSI fabrication and prototype hardware implementation. All these three teamswillworkundersupervision oftheteamleader.Nominalgroup sizewillbe3foreachteam The developed technology could possibly be utilized for both mainstream computer processors aswellasprocessorsadaptedfor low power micro devices such as mobilehandphones,smartphones, ipad,tabletPCsetc Possible High Impact Journals forPublications IEEETransactionsonComputers IEEE Trans on Circuits and Systems Jnl of Computer and System Sciences Integration:TheVLSIJnl TheoreticalComputerScience Collaborators Rezaul Alam Chowdhury, Stony BrookUniversity,NewYork,USA. HIR Annual report 2011.indb 121 24/05/2012 9:44:57 122 High Impact Research Annual Report 2011 Project No: UM.C/HIR/MOHE/FCSIT/05 Title: Multimodal Engagement For Children With Communication Disabilities Principal Investigator : Professor Dr Siti Salwah Salim Faculty : Department of Software Engineering, FCSIT SummaryofResearchProposal The term communication disabilities refer to speech impairments such as stuttering,impairedarticulationoravoiceimpairmentthatadverselyaffects a child’s educational performance. This research focuses on two types of communication disabilities among children – speech disorders and autism. Speech disorders involve problems such as difficulties in making speech sounds.Autismontheotherhandreferstoneuraldevelopmentimpairments characterized by damaged communication and social interaction. With the advancementintechnologythesechildrencanimprovetheircommunication capabilitybyusingcommunicationdevicesthatenablevocalcommunication. Thesecommunicationdeviceswouldpotentiallyimprovethecommunication ability of these children. However, the existing systems, software tools and devicesareprofoundlyinadequatetomeettheseobjectives. The experiments with traditional speech recognition models show a wordlevelaccuracyoflessthan4.5percentondisorderedspeechcomparedwith 84.8percentonnon-disorderedspeechusingasmallvocabulary.Toimprove the performance of existing software tools, we need to better understand the speech of these children in order to analyze and identify common speech errors (low volume, variable rate and rhythm, irregular pitch, clarity, voicequality,lowintelligibilityandfluency).Theknowledgegainedfromthis understandingcanbeappliedforthedevelopmentofbettermodelsthatcan accuratelypredictwhatthesechildrenaretryingtosay. Objectives Methodology This research is sub-divided into fourvisibleprojects.Thefirstsubproject will be the development of a Malay automatic speech recognitionsystem(ASR)basedon the Hidden Markov Model (HMM) torecognizethespeechofchildren withspeechdisorders.Thesecond sub-projectwillbetheapplication oftheMalayASRforchildrenwith speech disorders in the area of children’sentertainment,especially for game-based applications, with a view to improving their communicationability This project will carry out a literature review to identify and comprehend the related research studies in the area of speech recognition and communication disabilities among children to identify the problem of existing communication-assistive tools for children with communication disabilities. An empirical analysis willbecarriedoutonchildrenwith speech disorders and autism by collectingexistingspeechdisorder databases for other languages andbyusingacollectionofMalay databases of disordered speech uttered by children with speech disorders, their communication behaviour and their needs from special schools or centres using video recording and audio recording tools. Based on the evidenceandinformationgathered from the empirical analysis this research will define feasible techniques and modalities from the understanding gained from the review of the collected data. The identified techniques and modalitieswillbeusedtodevelop a Malay ASR that can perform The third sub-project will be the development of a speech error detection and corrective model that will detect and correct the speech recognition errors of the Malay ASR by adopting a formal approach through the analysis and identification of the speech recognitionerrorsofthedeveloped Malay ASR. The final sub-project will be the development of an augmentative communication system that will ease and encourage communication development for children with autismimpairment HIR Annual report 2011.indb 122 the recognition of the speech of children with communication disorders.TheimplementedMalay ASR will be applied in a gamebasedapplicationtotrainchildren with speech disorders to improve their communication ability. The speech errors produced by the developed Malay ASR will be corrected using a speech detection and corrective model based on a formal approach. For childrensufferingfromautismthis research will design and develop an augmentative communication systemusingauser-centreddesign approach.Finally,theimplemented systemswillbeevaluatedthrough experimentalevaluation Outcome The collection of a Malay speech corpus and visual recordings of childrenwithspeechdisordersand autism A Malay speech recognition systemtorecognizethespeechof childrenwithspeechdisorders 24/05/2012 9:44:57 High Impact Research Annual Report 2011 Aformalapproachmodeltoreduce therecognitionerrorsoftheMalay ASRwhenrecognizingthespeech of children with communication disabilities A children’s entertainment gamebased application that improves theircommunicationability An augmentative communication systemforautisticchildren Possible High Impact Journals forPublications ComputersandEducation SpeechCommunication 123 Educational technology Research andDevelopment International Journal of Human ComputerStudies Collaborators Spastic Children’s Association of SelangorandFederalTerritory Sekolah Rendah Alam Shah, PetalingJaya The National Autism Society of Malaysia Prof. Shaoying Liu (Formal Engineering Methods), Hosei University,Tokyo JournalofBiomedicalInformatics Project No: UM.C/HIR/MOHE/FCSIT/07 Title: A Generic / Natural Language Expert System for Robotics and Bazaar Simulation Principal Investigator : Dr. Ng Liang Shing Faculty : Department of Artificial Intelligence, FCSIT SummaryofResearchProposal This proposal concerns 6 major fields of research concerning Artificial Intelligence: i. TuringTest ii. Semantics iii. Robotics iv. SearchEngine v. ExpertSystem vi. CloudComputing We seek to address the shortcomings of the these fields with a “unified framework”basedongraphtheory,whichcanbeoutlinedasfollow: i. “Thinking” can be represented as “an infinite loop of questions and answers”. ii. Questionasunconnectedgraph. iii. Answerasconnectedgraph. iv. Programcode(orequivalent)aslowlevelgraph. v. Relation/description,labelashighlevelgraph. We will use this framework to create a machine learning method that is similar to human learning i.e. Human babies learn by associating vision (representation of low level operations) with speech (labels or high level relations,whichinturnisthebasisoflanguage). WewillusetheaboveframeworktocreateanExpertSystemarchitecturefor “ProgramModifier”(aprogramthatmodifiesotherprograms.) We can also use the above framework to investigate the question “Is the Internet intelligent?” and provide a quantitative solution to the question of “Technological Singulartity” (the point in time when machine intelligence exceedsthatofhuman.) HIR Annual report 2011.indb 123 24/05/2012 9:44:57 124 High Impact Research Annual Report 2011 Objectives Methodology 1. Core AI Hierarchy) 2. 3. 4. 5. To produce an improved theoretical foundation of “machineintelligence”,which can also be used to analyse humanbehaviour Tocreateanimprovedtestfor “intelligence”,theIncremental Turing Test, that is based on “survival” and “competition forresources”,andapplicable to groups of human beings, computer networks and groups comprising human andmachines To develop a mathematical framework based on graph theory to address several fundamental issues in ArtificialIntelligence Todesignanovelarchitecture for Expert Systems comprising natural language and multimedia interface (GNLES: Generic / Natural Language Expert System) based on the unified graph theoreticframeworkin(3) To develop the Universal Data Exchange Architecture (UDEX, an extension of Unix pipe to Cloud/Grid/Internet) required for large scale simulationrequiredin(4) Engine Universal Data Architecture(UDEX) (Semantic Possible High Impact Journals forPublications ComputationalIntelligence Exchange IEEEtransactionsonfuzzysystems Artificialintelligence RoboticsSimulation Journal of Machine Learning Research BazaarSimulation Simulation of Gold Bullion Market andEconomy AppliedSoftComputing Collaborators Outcome Novel theories/New discovery/ Newknowledge i. A Unifying Graph Theoretic Framework for low level “operations” and high level “concepts”; Incremental TuringTest ii. Generic / Natural Language ExpertSystem(GNLES iii. ProgramModifier iv. Universal Data Exchange Architecture(UDEX) Dr Li Wei Feng, Tsing Hua University,China Dr Richard Dearden, Prof Aaron Sloman, Birmingham University, UnitedKingdom ResearchPublication: 15ISIjournalpapers SpecificorPotentialApplications AutonomousRobots Intelligent“NetBot” BazaarBusinessInfrastructure Gold/Silver/Commodity Currency Universal Data Architecture(UDEX) HIR Annual report 2011.indb 124 Digital Exchange 24/05/2012 9:44:57 High Impact Research Annual Report 2011 125 RESEARCH PROPOSAL (HIR-MoHE5Years) Chancellory Project No: UM.C/625/1/HIR/MOHE/CHAN/01 Title: Bacterial Quorum Sensing and Quorum Quenching Research Principal Investigator : Dr. Chan Kok Gan Faculty : Institute of Bilological Sciences, Faculty of Science SummaryofResearchProposal Infectiousdiseasesaccountformorethan13milliondeathsayearandare themaincausesofmortalityandmorbidityglobally.Althoughantibioticshave historicallybeenverysuccessful,theemergenceofmulti-antibioticresistant bacteriaandthefailureofdrugdiscoveryprogrammesoverthelast10years toprovidenewbroadspectrumantibioticswithtrulynovelmodesofactionis amajorthreattopublichealthworldwide. There is a compelling need to expedite anti-infective therapy and ideally a newmagicbulletisverydesirable.Indeedsuchamagicbulletdoesoccur: QuorumSensingwhichcanbeatargetedtoattenuatepathogenicbacteria, whichservesasthebasisfornon-antibioticdrugdiscovery. Objectives Methodology Quorumquenchingwhichinterferes were quorum sensing, represents an important way to regulate bacterialvirulencewithouttheuse of antibiotic. Quorum quenching can be achieved in 3 ways: (1) Degrading the autoinducer, (2) blockthesynthesisofautoinducer, and (3) block the receptor protein wheretheautoinducerbindto Hundreds of quorum quenching bacteria have been isolated from a selective medium (termed KG medium) designed by my group. Thesequorumquenchingbacteria representarichsourceofenzymes thatcaninterferequorumsensing. Natural products have also been explored in search of nonenzymatic approach, small active biomolecules that exhibit antiquorumsensingproperties All 3 ways eventually jam the bacteria from talking, which in turn, force-to-silent bacteria are unable to express their virulence determinants production, or attenuated without killing the bacteria, thus removing survival pressurethatevolutionhasproven to select resistant bacteria from emerging,orre-emerging Outcome Novel quorum quenching bacteria isolated Small,active,anti-quorumsensing biomolecules can serve as lead compound for novel anti-infective drugdesign Possible High Impact Journals forPublications EnvironmentalMicrobiology MicrobialEcology AppliedEnvironmentalMicrobiology Antimicrobial Chemotherapy Agents and BMCMicrobiology JournalofNaturalProducts Proceeding of National Academy ofScienceofUSA Collaborators ProfPaulWilliams(Nottingham) ProfYvesDessaux(CNRS,Paris) Assoc.ProfKohChongLek(NTU) DrSamChoonKook(NTU) ProfKalaiMathee(FIU,USA) HIR Annual report 2011.indb 125 24/05/2012 9:44:57 126 High Impact Research Annual Report 2011 Project No: UM.C/625/1/HIR/MOHE/CHAN/02 Title: Molecular Genetics Principal Investigator : Professor Dr. Jamuna Vadivelu Faculty : Department of Medical Microbiology, Faculty of Medicine SummaryofResearchProposal TheMolecularGeneticsprojectconsistsof8sub-projects: 1. Genetics of the Respiratory, Gastrointestinal, Central Nervous System andBlood-bornePathogens; 2. Genome-wideAssociationStudies(GWAS)forInfectiousDiseases; 3. InterspeciesMolecularCrosstalkinHelicobacter pyloriInfections; 4. Molecular Genetics and Antimicrobial Susceptibility Pattern in Local ClinicalHelicobacter pyloriIsolates; 5. International Network of Excellence on Chronological Evolution and Replicative Genomics of the Human Gastric Pathogen, Helicobacter pylori; 6. PathogenomicsandphenomicsofFoodborneBacterialPathogens; 7. RegulationofImmuneResponsebyEpigenetics;and 8. Genome Organization in Diseases: From Mutations to Structural VariationsandEpigenetics. Thesebroad-basedsubprojectswillcoverthegeneticsandmolecularbasis of various human infectious diseases and cancer from both microbial and hostperspectives. Objectives 1. 2. 3. 4. isolates in the Malaysian population;andtodetermine the relationship between genetic mutations and the prevalence of antibiotic resistance in the local population(sub-project4) To determine the complete genetic map for pathogens commonlyassociatedwiththe respiratory, gastrointestinal, central nervous system and blood-borne diseases (subproject1) To conduct genome-wide association studies (GWAS) that examine the human genetic variants that can be associated with immunity, susceptibility, progression, treatment response and recovery of infectious diseases(sub-project2) To study Helicobacter pylori interspecies communication bymeansofapredetermined bacterial consortium under controlled laboratory conditions, in germ-free mouse model and in human stomach; and to carry out in-depth analysis of proteins and metabolites that may be involved in molecular crosstalkandquorumsensing inthemultispeciescommunity (sub-project3) To analyze the molecular geneticbasisofantimicrobial resistance of H. pylori HIR Annual report 2011.indb 126 5. 6. 7. To investigate the genetic adaptation mechanisms of H. pylori after challenge in humans by means of whole genome sequencing and comparative genomics (subproject5) To identify the virulence factors and determinants that contributes to the acute and chronic systemic infections,aswellassurvival and persistence outside the human host; and to understand the genetics and mechanisms of adaptation and persistence of S. typhi in various systemic organs withinhumanhostandinthe environment(sub-project6) To link the genomic and phenotypicvariationbetween Salmonella Typhi and its closely related species, Salmonella Typhimurium and Salmonella Paratyphi A and B, to their differences in the virulence and disease manifestation(sub-project6) 8. To investigate the genomic and phenomic variation between Salmonella and Vibrios that contribute to the super-adaptive mechanisms of Vibrios that enables the pathogentopersistinhostile and changing environment (sub-project6) 9. To study the molecular mechanism of H3K9 methylation removal and EHMT1-mediated gene repression in an immune response; to explore the potential application of BIX01294 in cancer therapy; andtodeterminethefunctions ofPRDM11andJMJD8inthe immune response regulation (Sub-project7) 10. To study the genome organization of various cancers,e.g.nasopharyngeal carcinoma, lymphoma and multiplemyeloma 24/05/2012 9:44:57 High Impact Research Annual Report 2011 Methodology MassTaq PCR developed by ColumbiaUniversityandmolecular methods developed by CERiA for screeningofpathogens Full-lengthgenomesequencing Genome-wide association studies (GWAS)analysis Meta-proteomics and metametabolomics analysis using microfluidicliquidchromatography mass spectrometry system (ESIQTOF) PFGE,MLVA, AFLP analysis of selectedfoodbornepathogens QuantitativePCR Chromatin immunoprecipation (ChIP)analysis Meta-genomicsanalysis Copy number variation (CNV) analysis Epigeneticsanalysis High-throughput phenotypic microarray analysis of foodborne pathogen Bioinformaticsanalysis Outcome The complete genetic map for pathogens commonly associated with the respiratory, gastrointestinal, central nervous systemandblood-bornediseases willbedetermined Humangeneticvariantsthatcanbe associatedwithdiseaseimmunity, susceptibility, progression, treatmentresponseorrecoveryto particular infectious diseases will beidentified Molecular crosstalk and quorum sensing between H. pylori and other Gram-positive and Gram-negative members of a multispecies bacterial consortium willbeidentified HIR Annual report 2011.indb 127 population; especially that of newer antibiotics that are not conventionally used in H. pylori treatmentcurrently Geneticadaptationmechanismsof H. pyloriafterchallengeinhumans andthewholegenomesequencing and analysis of H. pylori strains corresponding to three different ethnic groups in Malaysia will be determined The virulence factors and determinants of foodborne pathogens that contribute to the acute and chronic systemic infections, as well as the survival andpersistenceoutsideofhuman hostwillbeidentified Understanding the role of methylation in regulating NF-B activity, identify new co-activators orco-repressorsthatfine-tunethe transcriptionalactivityofNF-B. Identifying of genetic polymorphism associated with specific functional and clinical characteristics; genetic, structural variantsandepigeneticalterations that are associated with selected cancer susceptibility, immunity andprogression Possible High Impact Journals forPublications USA MartinBlaser,NewYorkUniversity, USA LingLu,UniversityofKansas,USA Thomas Briese, University,USA Columbia W.IanLipkin,ColumbiaUniversity, USA Hardie Kim, Nottingham,UK University of OliverG.Pybus,OxfordUniversity, UK Peter Simmonds, University of Edinburgh,UK Sven Pettersson, Institutet,Sweden Karolinska NaoyukiKamatani,RIKEN,Japan Yusuke Nakamura, University of Tokyo,Japan Yutaka Takebe, National Institute ofInfectiousDiseases,Japan DavidBooth,UniversityofSydney, Australia Hazel Mitchell, University of New SouthWales,Australia Sharon Lewin, Alfred Hospital, Australia Xueshan Xia, Kunming University ofScienceandTechnology,China Science Yi-Ming Arther Chen, National YangMingUniversity,Taiwan Nature ManfredRaida,A*STAR,Singapore NatureGenetics Seow Shih Wee, National Cancer CentreofSingapore,Singapore NatureImmunology 127 NewEnglandJournalofMedicine Ahmed Niyza, Hyderabad,India University Lancet MohdZakiSalleh,UiTM MolecularCell TehLayKek,UiTM PNAS AdeebaKamarulzaman,UM PLoSGenetics ChaiLayChing,UM MedicalGenetics CindyTehSuanJu,UM of EaChee-Kwee,Caltech/UM Collaborators GanGinGin,UM The molecular mechanisms of action of microbially generated metabolites on host cell proliferative/ apoptotic responses, cytokine production, inflammatory and immunomodulatory effects and pathogenesis will be determined David Baltimore (Nobel Laureate), Caltech,USA Understanding the prevalence rates of antibiotic resistance and genetic mutations in H. pylori isolates in the Malaysian Eric Delwart, University CaliforniaSanFrancisco,USA Barry Marshall (Nobel Laureate), University of Western Australia, Australia GohKheanLee,UM GopalaKrishnanA/LGovindasamy, UM AllanHildesheim,NationalCancer Institute,USA of FritzFrancois,NewYorkUniversity, 24/05/2012 9:44:57 128 High Impact Research Annual Report 2011 Project No: UM.C/625/1/HIR/MOHE/CHAN/03 Title: Understanding the Fundamental Aspects Through Molecular and Cellular Studies to Determine The Lineage Commitment Mechanisms Involed In Mesenchymal Stem Cells Differentiation for Potential Upscaling and Clinical Applications Principal Investigator : Professor Dr. Tunku Kamarul Zaman Faculty : Department of Orthopaedic Surgery, Faculty of Medicine Summaryofresearchproposal Project1:Contingentgeneregulatorynetworksinchondrogenesis: Chondrogenesis is a stringently regulated, multistep cellular differentiation program culminating in acquisition of the chondrocytic phenotype. The process of chondrogenesis occurs in stages beginning with mesenchymal cell recruitment and migration, proliferation and condensation, which are regulated by mesenchymal- epithelial cell interaction. Several regulatory factors have been identified to play a role in chondrogenesis, including the positive transacting factors of the SOX family such as SOX9, SOX5, and SOX6,aswellasnegativetransactingfactorssuchasC/EBPanddeltaEF1. However,acompleteunderstandingoftheintricateregulatorynetworkthat governsthetissue-specificexpressionofcartilagegenesisnotyetavailable. Hencethecurrentprojectisintendedtoidentifythecontingentgeneregulatory networkduringchondrogenesis. Project 2: PLLA/coll/HA Nano-fibrous scaffold for controlled delivery of recombinanthumanPDGF-BB: Plateletderivedgrowthfactor(PDGF)isamultifunctionalgrowthfactor,whose homo-orheterodimericmoleculesbindstotwostructurallyrelated,intrinsic tyrosine kinase receptors (PDGF-Rα and PDGF-Rβ) to exert its biological effects.Apartfromparticipatinginembryonicdevelopmentoforgansitalso playsaveryimportantroleinpostnataltissuerepair,regenerationanddisease development. PDGF possesses biological functions on cellular chemotaxis, mitogenesis, proliferation, extracellular matrix synthesis, anti-apoptosis and vascularization. As a potential therapeutic agent, PDGF has been widely studied both pre-clinically and clinically. Thus the study was proposed to develop PLLA/coll/HA nanofibrous scaffold incorporated with the growth factor (PDGF-BB) containing microspheres with the capacity of releasing bioactivePDGF-BBinawell-controlledmannerandinducingosteogenesis. Project3:TreatmentofDiabetesMellitususingAdiponectinsecretionobtained fromGeneticallyModifiedMesenchymalStemCell: Geneandstemcelltherapiesbythemselvesholdpromiseforthetreatment of a variety of human disease, but combinations of these approaches may be even more useful for certain disorders. Adiponectin has been found to increase insulin sensitivity of tissues and it decreases in diabetes type II patients. Genetically modified MSC have the potential to distribute human adiponectininsystemiccirculation.Inthisregardthisprojectattemptstouse genetically modified MSC as a cell base therapy for potential treatment in diabetes.Theresultofthisstudycanprovideessentialinformationleadingto thepotentialuseofmesenchymalstemcellsfortreatingthischronicdisease. Project4:Roleofadiponectinininducing/promotingtenocyteprogenitorcell proliferationanddifferentiation: Adiponectinisahormoneresponsibleinmodulatinganumberofmetabolic processes, which includes glucose regulation and fatty acid catabolism. Although it has also been shown that this protein induces the proliferation and differentiation of many progenitor cells including endothelial cells, hematopoietic stem cells and osteoblasts, its role in inducing tenocyte progenitorcells(TPC)hasnotbeenpreviouslyelucidated.Hencethisstudy is designed to investigate the effects of adiponectin on the differentiation and proliferation of tenocyte progenitor cells and the possible downstream signalingpathway.Itissuggestedthatadiponectinmaybeconsideredasa potentialtherapeuticagentfortendon-relateddiseases. HIR Annual report 2011.indb 128 24/05/2012 9:44:57 High Impact Research Annual Report 2011 Objectives Methodology Project 1: To understand the genes that are upregulated or downregulated at different time points of chondrogenesis and to identify the contingent gene regulatorynetworkthatcanleadto thedifferentiationofMesenchymal stemcellstoChondrocytes Project 1: Mesenchymal stem cells will be isolated from bone marrow and characterized by FACS.Themicroarrayanalysiswill be performed for profiling gene expression at epiphysis, resting, proliferative, transitional and hypertrophicstage.Tovalidatethe microarraydatausingindependent methods, novel markers will be selected for analysis of gene expression using RT – PCR and FACS to detect the actual gene expression during different time points. The gene loss function using SiRNA will be carried out to understand the functional hierarchyofupregulatedgenes Project 2: To develop a PLLA/ coll/HA Nano-fibrous scaffold for the controlled delivery of human recombinant PDGF-BB and its potential role in inducing osteogensis Project 3: The objective of this studyistousegeneticallymodified MSCs to secrete adiponectin to compliment the endogenous adiponectin with the aim to ameliorate diabetes symptoms in diabeticrats Project 4: The objective is to investigate the effects of adiponectin on the differentiation and proliferation potential of tenocyte progenitor cells and to study the possible downstream signalingpathwaysinvolvedinit Project 2: The PLLA/HA, PLLA/ coll, PLLA/coll/HA nanofiberous scaffold will be prepared using the electrospinning technique and PLGA microspheres. FITC-BSA or PDGF-BB will be incorporated into PLLA nano-fibrous scaffolds using a post-seeding method. The morphology and distribution of microspheres in scaffold were examined using SEM and laser scanning confocal microscopy. After characterization, the MSCs willbeseededontothescaffolds andgrowninosteogenicmedium, at different time points the cell will be harvested, RNA was isolated and the osteogenic gene expressionprofileswillbestudied using Realtime PCR and PCR arraytechniques Project 3: A recombinant plasmid containing GFP and in vitro constructed adiponectin gene using overlap extension PCR of exon1 and exon2 will be constructed and transfected into MSCs.Thesegeneticallymodified adiponectin secreting MSCs will be screened for adiponecting secretion and these cells will be injected into diabetic rats, while thenormalMSCservesascontrol. After treatment period the blood glucose,adiponectinlevelandthe lipidprofilewillbeanalysed Project 4: Adiponectin gene will be constructed using gene overlap extension PCR and cloned into E. coli to express as periplasmic protein, which will be purifiedandconfirmedbywestern blotting using anti-adiponectin antibody. The adiponectin will be added to Tenocyte progenitor cells culture and the proliferation HIR Annual report 2011.indb 129 129 and differentiation potential of adiponectinwillbeanalysed.Real time PCR analysis of tenogenic genemarkerswillbeperformed Outcome Better understanding of the contingent gene regulatory networksduringchongrogenesis. Abetterscaffoldwiththecontrolled releaseofgrowthfactorwhichcan supportosteogenesis New generation treatment strategies using genetically modified stem cells can be used fortreatingdiabetesmellitus Adiponectin can be used as a growth factor for promoting tenocyte proliferation and differentiation and it can be possibly used in clinical trials for tendonrelateddiseases Possible high impact journals forpublications OsteoarthritisandCartilage JournalofBoneandJointSurgeryAmericanVolume JournalofOrthopedicResearch JournalofBoneandJointSurgeryBritishVolume American Medicine Journal of Sports Collaborators Prof. Dan Badder, School of Engineering and Material Science QueenMary,UniversityofLondon (QMUL),UnitedKingdom Assoc.Prof.JamesWang,Director oftheMechanoBiologyLaboratory, Department of Orthopaedic Surgery,UniversityofPittsburgh Dr. Chim C Lang, Centre for Cardiovascular & Lung Biology, Division of Medical Sciences, College of Medicine, Dentistry & Nursing, Ninewells Hospital & MedicalSchool 24/05/2012 9:44:57 130 High Impact Research Annual Report 2011 Project No: UM.C/625/1/HIR/MOHE/CHAN/04 Title: Quantum and Laser Science Principal Investigator : Associate Professor Dr. Raymond Ooi Faculty : Department of Physics, Faculty of Science SummaryofResearchProposal Our research develops future technologies that will be driven by light or photons.Itinvolvesengineeringquantumpropertiesoflightandmatter.We explore thefundamental propertiesoflight inexoticopticalmaterialssuchas nanostructuresandmetamaterialstobringinnovationinopticalscienceand technology.Theresearchinterestofthegroupisthecontrolandmanipulation of quantum systems that exhibit quantum mechanical effects such as entanglement,quantumcorrelationsandquantuminterference.Theseeffects areusefulforperforminghighprecisionmeasurements,metrology,quantum computing, communication and cryptography. Our research uses surface plasmon to achieve smaller, efficient, faster and more sensitive all-optical devicesforvariousapplicationsespeciallyforsensingsinglemolecules,high resolution imaging and ultrafast optical switching, reliable transmission of quantuminformationinconfinedenvironment. Another aspect of our research concerns the interaction of high-intensity andultra-shortlaserpulseswithmatter,thegenerationofultra-shortpulses and the study of dynamical quantum proceses in atomic, molecular and opticalsystems.Wealsostudyultracoldmatter,suchaslaser-cooledatoms, molecules, and novel properties quantum fluids which are useful for ultra precisespectroscopyandtime-frequencystandard. Objectives Methodology To develop state-of-the art researchinvolvingquantumoptics, optical materials and advanced laser science, particularly to study quantum coherence and correlation in light and matter at theatomiclevel We develop theory and computational capabilities to study the physics in the a) generation, b) propagation and c) interactions of novel light sources in photonic structures and quantum systems. This research involves mathematical modeling and theoretical study. Hence, the research involves the mathematical development of the proposed formulation and the skill of mathematical analyzing in order to implement and solve the nonlinear equations. A substantial amount of study is involved in developing the key framework in nonrelativisticquantummechanics and quantum electrodynamics. These formalisms enable the calculations to be performed rigorously for light matter interaction, ultra-high intensity laser propagation, nonlinear effects in wave propagation and ultra-intense laser generation. Thesimulationofopticalmaterials may involve developing manybody quantum theory, a topic of crucial importance in fields ranging from quantum chemistry and biochemistry to the study of advanced materials such as graphene, high-temperature superconductors and carbon To develop and apply a combination of cutting-edge techniques to model dynamical properties of photons, molecules and nanostructures interacting withintenselaserfields HIR Annual report 2011.indb 130 nanostructures. This research must also include the use of computingskillsandsimulationsin MathematicaorMatlabtoproduce analytical results and numerical results In the case of ultra-high intensity laser a lot of amazing nonlinear effects can be studied by combining nonlinear optical processes with quantum optics. The production of the ultra-high energy pulse through nonlinear interactions and high harmonic generation lead to an efficient generation of coherent X-ray pulses.Atextremelyhighintensity, the electromagnetic waves in the vacuumcannolongerbeexplained by the ordinary electrodynamic theory. The Maxwell’s equation has to be modified to include nonlinearity of quantum vacuum. Besides, the ultra-high intensity laserinthenonlinearvacuum,such laser can interact between each other when they overlap. Hence, the process leads to the creation of photon-photon scattering and photon splitting can be studied in detail. The whole process would be very interesting since it has not been fully explored until very recently 24/05/2012 9:44:57 High Impact Research Annual Report 2011 Outcome Collaborators This is a programme of advanced research with potential for high scientific impact and applications to areas of strategic importance such as advanced information technology, novel light sources with new applications, renewable energy and biomolecular technology QihuangGong-PekingUniversity Paul Berman, Michigan University Andre Bandrauk, University 131 of Sherbrooke Noriah Bidin, University TechnologyMalaysia of Possible High Impact Journals forPublications PhysicalReviewLetter, PhysicalReviewA Project No: UM.C/625/1/HIR/MOHE/CHAN/05 Title: Fundamental Sciences of Self-Assembly Principal Investigator : Professor Dr. Rauzah Hashim. Faculty : Department of Chemistry, Faculty of Science SummaryofResearchProposal Molecularself-assembliesfromlowmolarmassliquidcrystals(thermotropic and lyotropic) are widely used in nanotechnology and life sciences. Many well-known thermotropic applications include flat panel display devices, while lyotropic liquid crystals are found pervasively in living systems and their commercial applications include surfactants and emulsifiers. We have conducted a wide range of research on self-assembly phenomena includingsynthesizingaspecialclassofnon-ionicandenvironmentalfriendly surfactantsbasedonglycolipid.Glycolipidsbelongtoaclassofliquidcrystal material termed amphitropic since they can show both thermotropic and lyotropic liquid crystalline properties. Hence the potential applications of thesematerialsarefarwiderthantheconventionalthermotropicorlyotropic liquidcrystalsencompassingbothhigh-technologyindustryandlifesciences. Ouremphasishasalwaysbeenunitingtheapproachesinexperiment,theory and computation to gain knowledge in the structure-property relationship. In liquid crystals science, the basic understanding of the phase behaviour andhowtomanipulatethemwiththeexternalfactorsareimportantandthe interplay of these spearhead many innovative ideas in technology. In the ensuinginvestigation,theprogramofFundamentalSciencesofSelf-Assembly, broadensitsscopebyincludingotherfundamentalstudiesonstructureand ultrafastdynamicstoexploremicro-environmentoflipidicsystemaswellas exploringapplicationsindeliverysystems,thinfilmforIR-sensorandinfuture materialsforproteincrystallization. HIR Annual report 2011.indb 131 Objectives Methodology With this basic knowledge in structure-property relationship, currentlywecontinuetosynthesize several novel liquid crystals including thermotropic (eg. metellomesogens), amphitropics (eg, crown-ether glycolipids), triazole glycolipids compounds and chromonics (sugar derived) liquidcrystals The present program focuses on the followings: novel materials for self assembly and related phenomena (synthesis approach and design). The self-assembly structures of these materials are studied by diffraction and scattering techniques (eg. SWAXS, SANS and synchrotron). Some basic dynamics of self- assembly will be determined by using deuterium NMR and time-resolved fluorescence spectroscopy. acroscopic and microscopic theories for selfassembly phenomena. Aspects of modeling and simulation will be included to get detailed structure property relationship. Nanoelectronic property of selfassembly and investigation on the effect of external perturbation 24/05/2012 9:44:58 132 High Impact Research Annual Report 2011 (eg. field effect) on self-assembly will be attempted. Finally, we shall also focus on applications of nanostructure self-assembly and formulation in a few cases includingdrugdelivery. Outcome Producing novel materials for improvedformulation Possible High Impact Journals forPublications JournalofPhysicalChemistryC, Langmuir, Nanomedicines Collaborators Dr.SimYokeLing,UniversitiTunku AbdulRahman Prof.OsamaAbou-Zied,Chemistry Department, Sultan Qaboos University,Oman Prof. John M. Seddon, Chemistry Department, Imperial College London UniversityUniversity,Oman Prof. A. Sugimura, Osaka Sangyo University Prof. Ou-Yang Zhong-Can, ChineseAcademyofScience Prof.C.Solans,CSIC,Barcelona Dr.Mehrdad,Iran Dr. R. Bryce and Prof. G. Tiddy, ManchesterUniversity Dr. M. Hato, Riken Yokohama, Japan Prof. Mitsumasa Iwamoto and Prof. H. Takezoe, Tokyo Institute ofTechnology LiquidCrystals Prof. Hiroyuki Minamikawa, AIST, Tsukuba CarbohydrateChemistry Prof.G.R.Luckhurst,Southampton Project No: UM.C/625/1/HIR/MOHE/CHAN/06 Title: Breast Cancer Project Principal Investigator : Professor Dr. Yip Cheng Har Faculty : Department of Surgery, Faculty of Medicine SummaryofResearchProposal BreastcanceristhecommonestcancerinMalaysianwomen,comprising31% ofcancersinwomen.(NSR2003-2006).ThebreastunitinUniversityMalaya MedicalCentrestartedresearchintotheepidemiologyofbreastcancerwith anIRPAresearchgrantin1994,continuingintoresearchintobreastcancer geneticswithCARIFin2003,andlaterintoresearchintopsychosocialissues. Breast cancer pathology, particularly in the ER, PR and HER2 was also studied,andseveralpublicationshavebeenproduced. WiththeawardoftheHIRgrantfortheBreastCancerProjectinAug2011, research has been divided into 5 programmes ie the Clincial Epidemiology programme (includes the Malaysian Breast Cancer Cohort study and the Breast Health Initiatives Study), the Genetics Programme, the Pathology programme,theInvestigatorInitiatedTrials(IIT)programme,andtheImmune Therapeutics (ITL) Programme. Each of these programmes has their own leaders,andProfessorCHYipistheoverallPrincipalInvestigator. Objectives The objectives of this project are to answer the following research questions: 1. Clinical Epidemiology: Why do Malay women have poorer survival? Is it lifestyle or is it genetics? What are the prognostic models that may work well in the Asian population? HIR Annual report 2011.indb 132 2. Genetics: Are there other highriskgeneticmutationsin the multiethnic population in Malaysia and how do these interactinbreastcancerrisk? 4. Investigator Initiated Trials: Are there novel treatment strategies that may improve outcome in women with breastcancerinMalaysia? 3. Pathology: Are there differences between triple negative breast cancer in Malaysians compared to Caucasiansandwhatarethe determinants of outcome in triplenegativebreastcancer? 5. Immune Therapeutcis: How can we monitor the immune response that occurs with novel therapeutics agents suchastheHER2vaccine? 24/05/2012 9:44:58 High Impact Research Annual Report 2011 Methodology Each programme has several individual projects, that is designed to answer each of the research questions. The methodology of each project and output is discussed with regular research meetings. International collaboration is developed within each programme. Each programme can recruit new projects if the investigator feels that it can lead to a meaningful outcome ie publication in a high impact journal. Audit of each projectwillbecarriedoutduringthe regular meetings. Collaborations withinthecountryareencouraged, and networking is encouraged to identify international collaborators whoareexpertsinthearea,toadd tothosewhoarealreadyinthelist ofcollaborators Outcome Better understanding of breast cancer in Malaysian women, in terms of risk factors, ethnicity, genetics, pathology, psychosocial barrierstoeffectivetreatment,and prognosisbasedonthesevarious 133 features. Development of new treatment strategiesforbreastcancer Possible High Impact Journals forPublications LancetOnocogy EuropeanJournalofCancer WorldJournalofSurgery Breast Cancer Research and Treatment BreastCancerResearch Collaborators NationalUniversityofSingapore UniversityWestofEngland Utrecht Medical Netherlands Centre, UniversityofCambridge,UK KarolinskaInstitute,Sweden QueensUniversityBelfast,Ireland UniversityofLeeds,UK Uniformed Services University of theHealthSciences,USA Project No: UM.C/625/1/HIR/MOHE/CHAN/07 Title: Integrated Photonics for Biosensors Principal Investigator : Associate Professor Dr. Faisal Rafiq Mahamd Adikan Faculty : Department Of Electrical Engineering, Faculty of Engineering SummaryofResearchProposal Optical fibres helped revolutionize medicine when they were first used to illuminate endoscopes in the 1960s. The result was the development of minimallyinvasivetoolsthathavebecomeessentialformedicaldiagnosisand surgery.Interestingly,theconceptofintegratedopticswasalsointroducedin the60s,pavingwaytomultifunctionalchipsthesizeofaricegrain.Oneofthe mostimportantandgrowingareasthatmakesignificantuseofthesechipsis insensing,inparticularbio-sensing.Thisledtotheintroductionofsuchterms asbiosensors,biochips,andlab-on-chip.Thesechipscanbelooselydefined as a collection of miniaturized test sites (microarrays) arranged on a solid substratethatpermitsmanyteststobeperformedatthesametimeinorder toachievehigherthroughputandspeed. In medical applications, optical based sensors offer many advantages over conventional sensors: they are small, immune from electromagnetic interference(EMI),haveincreasedsensitivityandareveryrobust. Thechallengeistodesignandproduceanin-situ,real-time,easytouse,simple andcheapsensorsystemthatareabletodetectinfectiousorcommunicable diseases caused by the presence of pathogenic microorganisms, such as bacteria, viruses, and parasites. These diseases include dengue fever, malaria,chikukunya,andtuberculosis. HIR Annual report 2011.indb 133 24/05/2012 9:44:58 134 High Impact Research Annual Report 2011 Objectives Methodology To develop biosensors/biochips for use in detecting infectious diseases by extending the combined capabilities of Flat Fibres, laser written polymer layers,micromachining/milling,and surface treatment of substrates withbindingagents Phase1:Designandfabricationof basicdetectionsystemsbasedon: To push the limit of sensing by attempting to detect the presence of viruses/micro-organisms before theycoagulateintoRNAs/antigens i. optofluidics/microfluidicsand spectroscopy,and ii. gratings (long period and Bragg) This phase will also involve chip functionalisation via surface treatment to improve both sensitivity and selectivity of the sensors.Thesensorswillbetested usingdenguevirusserotypes Wewillalsoinvestigatetheoptical, magnetic,andelectricalproperties of these serotypes, in order to assess if it is possible to employ field assisted techniques such as electrophoresis to further improve thesensorperformance Phase2:Designandfabricationof novel sensor chip based around FlatFibreandlaserwriting Thechipswillseetheincorporation of capillaries, and the use of micro-milling techniques to improve interaction between the electromagnetic field confined within the transport medium (evanescent) and the test specimens This stage will also explore featuresuniquetoFlatFibressuch asmulti-layerwaveguidance,and asymmetricexcitation Phase2willgohand-in-handwith the current work in producing ultra flexible, multi-structured Flat Fibre chips. A number of novel fabrication techniques will be tested in order to explore the possibility of incorporating as many functionalities into the Flat fibre. Furthermore, the ability to achieve as many functionalities within a single fabrication run is alsotargetedinordertoreducethe costperchip HIR Annual report 2011.indb 134 Phases 3 will simultaneously take place Phase3A:Detectionofvirus Upon completion of the above two phases, we would be able to determine the capability of our chips. This stage, which is the most ambitious, attempts to sense the onset of infection at its earliest stage, thus improving the survivability, and disease management Phase 3B: System integration – chipwithsensorinterrogator Engineeringacheap,fullyflexible, disposablechipthathastheability todetectthevariousstagesofthe dengueinfection Outcome Disposable, point-of-care sensor chipsandmodules; Expertise in optical chip making – based around polymer and Flat Fibre: formation of a spin-off high techcompany Possible High Impact Journals forPublications ThinSolidFilms; OpticsExpress; OpticsLetters; AppliedPhysicsLetters; NaturePhotonics; Lab-on-Chip Collaborators Prof. Faidz Rahman, Dr Loh Han Chern(UTAR) DrMukhzeerShahimin(UNIMAP) ProfMohdAdzirMahdi,DrNizam Tamchek(UPM) Prof Peter GR Smith, Dr James Gates (Optoelectronics Research Centre,UniversityofSouthampton) 24/05/2012 9:44:58 High Impact Research Annual Report 2011 135 Project No: UM.C/625/1/HIR/MOHE/CHAN/08 Title: The In Vivo Target Specificity and Function of HOX Proteins Principal Investigator : Dr. Lawerence Choo Siew Woh Faculty : Dental Research & Training Unit, Faculty of Dentistry SummaryofResearchProposal The Hox genes form a genetic code for generating morphological diversity alongtheantero-posteriorbodyaxisduringanimaldevelopment.Inaddition tothemorphogenesis,Hoxgeneshavealsobeenshowntolinktooncogenesis andhumandiseases.AllHoxgenesencodehighlyconservedDNA-binding homeodomainandhavebeenshowntobindtoverysimilar/samesequences in vitro (poor specificity) despite having distinct functions in vivo (high specificity). Although they have been shown to regulate a wide variety of downstream processes, direct transcriptional targets have been difficult to identifyandthishasbeenamajorobstacletoourunderstandingofHoxgene functionandhowthesegenesexecutethecodeinmorphogenesisoreven theirlinkwithhumandiseases/cancerswhichisstillnotwellunderstood.Our groupisinterestedtostudyhowHoxgeneticcodeworks. Objectives Methodology Outcome TodecodehowHoxgeneticcode works, we will embark on several aspects of fundamental research inthisprogramme:(1)understand thebasisoftheHOXspecificity,for example, by mapping the binding sites of different HOX proteins in the Drosophila cell lines, as a model system. (2) the roles/ functions of HOX transcription factors in development and gene control, (3) to identify their target genes which will give us insights into how HOX proteins execute their functions, (4) the association between chromatin states and HOX target selection, and (5) the influence of cofactors on HOX targetspecificity We map the binding profiles of different HOX proteins in the Drosophila genome across different time-points using whole genometilingarrays.Thegenomewide expression profiles are also generated across different timepoints.Byintegratingthebinding and expression profiles, we could look for functional target genes directlyregulatedbyHOXproteins and study the transcriptional outputs determined by different HOXtranscriptionfactors Better understanding of the specificityandrolesofHoxproteins Extensive bioinformatic anayses will be performed to identify HOX-bound regions, target genes, and to be used for other downstream analyses. The enrichment profiles of different histone modification marks will be determined at a genome-wide scale using established ChIP-onCHIP technology. By identifying the genomic regions marked by theserepressive/activationhistone marksandassociatedtargetgenes on genome-wide scale, we have an opportunity to compare and associatetheHOXbindingprofiles withchromatinstatesreflectedby thesehistonemodificationmarks PLoSBiology In addition to the HOX projects, we are also working on various bioinformatics-related projects covering the following major areas: software, database and pipelinedevelopment,bioimaging, comparative genomics, and Next Generation Sequencing (NGS) projects such as exome sequencing, RNA-seq, genome assembly and annotation, and metagenomics Better understanding of the dynamicsofHOXproteinbinding Hox genes are conserved among animals,anynewknowledgefound in this study could be applied to Humansorotherorganisms PossibleHighImpactJournalsfor Publications Nature BMCBiology PNAS PloSONE Collaborators Steven Russell, Department of Genetics,UniversityofCambridge, United Kingdom Robert White, Department of Psychology, University of Cambridge, United Kingdom Rita Colwell, John Hopkins University/UniversityofMaryland, USA Tom Cebula, John Hopkins University,USA Lee Hwee Kuan, Bioinformatics Institute, SingaporeCheng Li, BioinformaticsInstitute,Singapore Ngeow Yun Fong, Faculty of Medicine, University of Malaya ChanKokGan,FacultyofScience, UniversityofMalaya Chen Yeng, Faculty of Dentistry, UniversityofMalaya HIR Annual report 2011.indb 135 24/05/2012 9:44:58 HIR Annual report 2011.indb 136 24/05/2012 9:44:58 High Impact Research Annual Report 2011 137 PHOTO GALLERY INTERNATIONAL COLLABORATORS LIST OF PUBLICATIONS HIR GUIDELINES SOP FOR THE MANAGEMENT OF HIR FUND PROCUREMENT PROCESS GUIDELINES ON TECHNICAL EVALUATION HIR Annual report 2011.indb 137 24/05/2012 9:44:58 138 High Impact Research Annual Report 2011 HIR Annual report 2011.indb 138 24/05/2012 9:44:59 High Impact Research Annual Report 2011 HIR Annual report 2011.indb 139 139 24/05/2012 9:44:59 140 High Impact Research Annual Report 2011 HIR INTERNATIONAL COLLABORATORS 1. BurnetInstitute,Australia 39. UniversityMedicalCentreUtrecht,Netherlands 2. RMITUniversity,Australia 40. UniversityofOtago,NewZealand 3. CurtinUniversity,Australia 41. UniversityofAuckland,NewZealand 4. SydneyUniversity,Australia 42. UniversityofJos,Nigeria 5. UniversityofMelbourne,Australia 43. SultanQaboosUniversity,Oman 6. UniversityofWesternAustralia,Australia 44. UniversitateaBabes-Bolyai,Romania 7. UniversidadeFederaldeSãoCarlos,Brazil 45. KingSaudUniversity,SaudiArabia 8. McGillUniversity,Canada 46. AlexandraHospital,Singapore 9. UniversityToronto,Canada 47. NationalUniversityofSingapore,Singapore 10. UniversityofCalgary,Canada 48. UniversityofPeradeniya,SriLanka 11. UniversitédeSherbrooke,Canada 49. LuleaUniversityofTechnology,Sweden 12. HongKongUniversity,China 50. NationalYang-MingUniversity,Taiwan 13. BeijingGenomeInstitute,China 51. NationalChungHsingUniversity,Taiwan 14. ChineseUniversity,HongKong,China 52. SirnakUniversitesiRektorlugu,Turkey 15. Xi’an Jiaotong-Liverpool University, Jiangsu, China 53. UnitedArabEmiratesUniversity,UAE 54. BristolUniversity,UnitedKingdom 16. Kunming Institute of Science and Technology, China 55. UniversityofBath,UnitedKingdom 17. PekingUniversityHealthScienceCentre,Beijing, China 57. UniversityofSussex,UnitedKingdom 56. UniversityofSurrey,UnitedKingdom 18. UniversityofTartu,Estonia 58. CambridgeUniversity,UnitedKingdom 19. LavalUniversity,France 59. UniversityofSheffield,UnitedKingdom 20. EcoleCentraledeNantes,France 60. KingsCollegeLondon,UnitedKingdom 21. IITRoorkeeIndia 61. UniversityofLiverpool,UnitedKingdom 22. NITTiruchirappalli,India 62. UniversityofManchester,UnitedKingdom 23. ChristianMedicalCollege,India 63. UniversityofHertfordshire,UnitedKingdom 24. JawaharlalNehruUniversity,India 64. UniversityCollegeLondon,UnitedKingdom 25. IndianInstituteofTechnologyMadras(IITM),India 65. UniversityofSouthampton,UnitedKingdom 26. AirlanggaUniversity,Indonesia 66. UniversityWestofEngland,UnitedKingdom 27. SyiahKualaUniversity,Indonesia 67. YaleUniversity,USA 28. UniversityofSiena,Italy 68. A&MUniversity,USA 29. HoseiUniversity,Japan 69. UniversityofTexas,USA 30. KyotoUniversity,Japan 70. ColumbiaUniversity,USA 31. NihonUniversity,Japan 71. UniversityofMichigan,USA 32. HokkaidoUniversity,Japan 72. StonyBrookUniversity,USA 33. NagoyaInstituteofTechnology,Japan 73. UniversityofPittsburgh,USA 34. NationalInstituteofInfectiousDiseases,Japan 74. UniversityofSouthFlorida,USA 35. KobeUniversityResearchCenterforInlandSeas, Japan 75. PennsylvaniaStateUniversity,USA 36. UniversidaddeColima,Mexico 77. CancerInstituteofNewJersey,USA 37. LeidenUniversity,Netherlands 78. WilliamCareyUniversity,Mississippi,USA 38. LeidenUniversityMedicalCentre,Netherlands 79. UnitedStatesMilitaryCancerInstitute,USA HIR Annual report 2011.indb 140 76. UniformedServicesUniversity,USA 24/05/2012 9:44:59 High Impact Research Annual Report 2011 141 HIR PUBLICATIONS 1. AhmadyA,HashimMA,ArouaMK.Experimental Investigation on the Solubility and Initial Rate of Absorption of CO2 in aqueous Mixtures of Methyldiethanolamine with the Ionic Liquid 1-Butyl-3-methylimidazoliumTetrafluoroborate,J. Chem.Eng.Data.2010;55:5733-5738. 2. SairiNA,YusoffR,AliasY,ArouaMK.Solubilities of CO2 in aqueous N-methyldiethanolamine and guanidinium trifluoromethanesulfonate ionic liquidsystemsatelevatedpressures,FluidPhase Equilibria.2011;300:89–94. 3. Ahmady A, Hashim MA, Aroua MK. Solubility of Carbon Dioxide in the aqueous mixtures of Methyldiethanolamine with three types of Imidazolium-based Ionic Liquids, Fluid Phase Equilibria.2011;309:76–82. 4. Ahmady A, Hashim MA, Aroua MK. Density, viscosity,physicalsolubilityanddiffusivityofCO2 inaqueousMDEA+[bmim][BF4]solutionsfrom 303 to 333 K. Chemical Engineering Journal (in press). 5. Hamah-AliB,AliBA,YusoffR,ArouaMK.Corrosion ofCarbonSteelinAqueousCarbonatedSolution of MEA/ [bmim] [DCA], Int. J. Electrochem. Sci. 2011;6:181-198. 6. Lam SK, Burke D, Capeding MR, et al. Preparingforintroductionofdenguevaccine: Recommendationsfromthe1st Denguev2VAsiaPacificMeetingVaccine 2011;29:9417-22. 7. Lam SK, Burke D, Gubler D, Mendez-Galvan J, Thomas L. Call for a World Dengue Day Lancet December 2011; doi:10,1016/S01406736(11)61922-3. 8. 9. NgeowYF,WongYL,NgKP,OngCS,WahWah Aung. Rapid, cost-effective application of Tibilia TBRapidtestforcultureconfirmationofliveand heat-killed Mycobacterium tuberculosis. J Clin Microbiol2011;49:2776-2777. ChongPP,SelvaratnamL,AbbasAA,KamarulT. Human peripheral blood derived mesenchymal stem cells demonstrates similar characteristics and chondrogenic differentiation potential to bonemarrowderivedmesenchymalstemcells.J OrthopRes.2011Sept15doi:10.1002/jor.21556. 10. KrishnamurithyG,ShilpaPN,AhmadRE,Sulaiman S,NgCL,KamarulT.Humanamnioticmembrane as a chondrocyte carrier vehicle/substrate: in vitro study. J Biomed Mater Res A. 2011 Dec 1; 99(3):500-6.doi:10.1002/jbm.a.33184. 11. Appanna R, Ponnampalavanar S, Lum LCS See, Devi S. Susceptible and protective HLA class 1 alleles against dengue fever and dengue hemorrhagic fever patients in a Malaysian population.PLoSOne,2010.5(9). 12. Alhoot MA, Wang SM, Sekaran SD. Inhibition of Dengue Virus Entry and Multiplication into Monocytes Using RNA Interference. PLoS Negl TropDis.2011;5(11):e1410.doi:10.1371/journal. pntd.0001410. HIR Annual report 2011.indb 141 13. KufianMZ,AzizMF,ShukurMF,RahimAS,Ariffin NE,ShuhaimiNEA,MajidSR,YahyaR,ArofAK. PMMA-LiBOB Gel Electrolyte for Application in LithiumIonBatteries,SolidStateIonics,2011.(In press). 14. Vincent-Chong VK, Ismail SM, Rahman ZAA, SharifahNA,AnwarA,PradeepPJ,Ramanathan A, Karen-Ng LP, Kallarakkal TG, Mustafa WMW, Abraham MT, Tay KK, Zain RB. Genome wide analysis of oral squamous cell carcinomas revealed over expression of ISG15, Nestin and WNT11.OralDisease2011(inpress). 15. Ismail MA, Tamchek N, Muhammad Rosdi AH, Dambul KD’ Selvaraj J, Abd Rahim, N, Sandoghchi SR, Adikan, FRM. A Fiber Bragg Grating-Bimetal Temperature Sensor for Solar PanelInverters.SENSORS2011;11:8665-8673. 16. Hassan MRA, Tamchek N, Abas AF, Johar RM, MahamdAdikanFR.Dual-phasesensingforearly detectionofprepregstructuralfailuresviaetched claddingBragggrating.SensorsandActuatorsA. Physical2011;171:126-130. 17. Mahamd Adikan FR, Sandoghchi S, Chong W, Simpson R, Mahdi MA, Webb A, Gates J, HolmesC.DirectUVWrittenOpticalWaveguides in Flexible Glass Flat Fiber Chips’, Journal of Selected Topics in Quantum Electronics, IEEE JournalofSelectedTopicsinQuantumElectronics 2011(inpress). 18. Chan YF, Sam IC, Wee KL, and AbuBakar S. Enterovirus 71 in Malaysia: A decade later. NeurologyAsia.2011;16:1-15. 19. Ayu SM, Lai LR, Chan YF, Hatim A, Hairi NN, Ayob A , Sam IC. Seroprevalence survey of Chikungunya virus in Bagan Panchor, Malaysia. AmJTropMedHyg.2010;83:1245-8. 20. SamIC,ChuaCL,ChanYF.Chikungunyavirus diagnosisinthedevelopingworld:apressing need.ExpertRevAntiInfectTher.2011;9:108991. 21. Zubir A, Kazi SN, Badarudin A. Numerical investigation of the effect of various thermopyhsical properties on convection heat transfer performance of flowing nanofluid in a circular tube. Applied Thermal Engineering, December2012.(Inpress) 22. Rubio-Godoy M, Paladini G, Freeman MA, García-Vásquez A, Shinn AP. Morphological and molecular characterisation of Gyrodactylus salmonis(Platyhelminthes,Monogenea)collected in Mexico from rainbow trout (Oncorhynchus mykiss Walbaum). Vet Parasitol 2011 Doi:10.1016/j.vetpar.2011.11.005. 23. UrawaS,FreemanMA,JohnsonSC,JonesSRM, Yokoyama H. Geographical variation in spore morphology,genesequencesandhostspecificity of Myxobolus arcticus (Myxozoa) infecting salmonid nerve tissues. Dis Aquat Org 2011 Oct;96:229-37.DOI:10.3354/dao02398. 24/05/2012 9:44:59 142 High Impact Research Annual Report 2011 24. KristmundssonÁ,HelgasonS,BambirSH,Eydal M, Freeman MA. Margolisiella islandica sp. nov. (Apicomplexa: Eimeridae) infecting Iceland scallop Chlamys islandica (Müller, 1776) in Icelandic waters. J Invert Path 2011 Nov; 108: 139-146.DOI:10.1016/j.jip.2011.08.001. 25. LimCL, HonarvarB,ThungKH,ParamesranR. FastcomputationofexactZernikemomentsusing cascaded digital filters. Information Sciences. 2011:181:3638-3651. 26. Chan KG, Atkinson Mathee K, Sam CK, S.R. Chhabra SR, M. Cámara M, C.L. Koh CL, WilliamsP.CharacterizationofN-acylhomoserine lactone degrading bacteria associated with the Zingiber officinale (ginger) rhizosphere: Coexistence of quorum quenching and quorum sensinginAcinetobacterandBurkholderia.BMC Microbiology 2011; 11: 51. doi:10.1186/14712180-11-51. 27. Wong CS, Yin WF, Choo YM, Sam CK, Koh CL, ChanKG.Coexistenceofquorumquenchingand quorumsensingintropicalmarinePseudomonas aeruginosa strain MW3A. World Journal Microbiology Biotechnology 2011 doi 10.1007/ s11274-011-0836-x. 28. Chong YM, Yin WF, Ho CY, Mustafa MR, Abdul Hadi AH, Awang K, Narrima P, Chong- CL, Appleton DR, Chan KG. Malabaricone C from Myristica cinnamomea Exhibits Anti-Quorum Sensing Activity. Journal of Natural Product. 2011, 74 (10), pp 2261–2264. DOI: 10.1021/ np100872k 29. Lim HN, Huang NM Loo CH. Facile preparation of graphene-based chitosan films: Enhanced thermal, mechanical and antibacterial properties, Journal of Non-Crystalline Solids. (In Press). 30. Huang NM, Lim HN, Chia CH, Yarmo MA, Muhamad MR, Simple room-temperature preparation of high-yield large-area grapheme oxide, International Journal of Nanomedicine, 2011;6:3443-3448. 31. ChandramathiS,SureshK,AnitaZB,Kuppusamy UR. Infections of Blastocystis hominis and Microsporidia in Cancer Patients: Are They Opportunistic?TransactionsoftheRoyalSociety ofTropicalMedicineandHygiene.(Inpress). 32. Chan KH, Chandramathi S, Suresh K, Chua KH, Kuppusamy UR. Effects of Symptomatic and AsymptomaticIsolatesofBlastocystisHominison ColorectalCancerCellLine,HCT116.Parasitology Research.(Inpress) 33. Tiekink ERT, Zukerman-Schpector J. Emerging supramolecular synthons: C–H…κ(chelate) interactions in metal bis(1,1-dithiolates). Chem Commun.2011;47:6623–5. 34. Zukerman-Schpector J, Otero-de-la-Roza A, Luanã V, Tiekink ERT. Supramolecular architectures based on As(lone pair)…κ(aryl) interactions.ChemCommun.2011;47:7608–10. HIR Annual report 2011.indb 142 35. Câmpian MV, Haiduc I, Lönnecke P, Tiekink ERT. Crystal and molecular structures of two triphenylleadxanthates,Ph3Pb(S2COR),R=Me and i-Pr, featuring weak intramolecular Pb...O interactions.ZKristallogr.2011;226:780–5. 36. NazirR,MazharM,WakeelT,AkhtarMJ,Siddique M, Nadeem M, Khan NA, Shah R. Pyrolysis Mechanism of Trisbipyridineiron(II) Chloride to IronNanoparticles.JThermAnalCalorim.2011 doi:10.1007/s10973-011-1919-5. 37. Ehsan MA, Tahir AA. Hamid M, Mazha M, Wijayanatha KGU, Zeller M. Deposition of iron titanate/titaniaceramiccompositethinfilmsfrom single molecular precursor. Inorganica chemical Acta.2011;376:189-194. 38. Sultan M, Mazhar M, Tahir AA Wijayantha KGU, Zeller M. Isostructural copper-zinc mixed metal complexes for single source CuZnO composite thinfilms:.DaltonTransections2011.doi10.1039/ c1dt10560D 39. Crystalline 3Cu-PbO ceramic composite thin films from Pb2(OAc)4(U-O)3Cu6(dmae)4Cl4. C7H8.1.7H2O:Muhammad Shahid,Mazhar Hamid,Muhammad Mazhar, Javed Akhtar, Matthias Zeller,Allen D.Hunter. Inorganic ChemistryCommunications.2011;14:288-291. 40. Alam N, Shahid M, Mazhar M, Aljassabi S, Zeller M, Hunter AD. Catena-poly[[[tetrakis(4methylpyridine-kN)copper(II))]-U-sulphatoK2O:O]4.393-hydrate. Acta Cryst. 2011; E67 : 375-376. 41. TajS,MuhammadMD,ChaudhryMA,MazharM. Lithium, rubidium and cesium ion removal using potassium iron(III)hexacyanoferrate(II) supported on polymethylmethacrylate(PMMA). J.Radioanal NuclChem.2011;288:79-88. 42. Alam N, Ehsan MA, Zeller M, Mazhar M, Arifin Z. Bis(O-n-butyl dithiocarbonato-K2S,S)bis(pyridine-kN)manganese (II). Acta Cryst. E67,m1064. 43. Alam N, Zeller M, Ahmed Tajidi NS, Arifin Z, Mazhar M. Catena-poly[[diaquabis(3-methylpyridine-kN)cobalt(II)]-u-sulphato-K2O:O’]..Acta Cryst.2011E67,m1065-1066. 44. TanWR,ChanCS,YogarajahP,CondellJ.AFusion Approach for Effecient Human Skin Detection, IEEE Transactions on Industrial Informatics. (In Press) 45. Arafat MM, Dinan B, Haseeb ASMA, Akbar SA. Gas Sensors Based on One Dimensional NanostructuredMetalOxides:AReview.Sensors (2012)(Accepted). 46. Zak AK, Abd. Majid WH. Effect of solvent on structure and optical properties of PZT nanoparticles prepared by sol–gel method in infraredregion.CeramInt.2011;37:753-8. 47. ZakAK,Abd.MajidWH,EbrahimizadehAbrishami M,YousefiR,HosseiniSM.X-rayanalysisofZnO nanoparticles by Williamson–Hall and size–strain plotmethods,SolidStateSci.2011;13:251-6. 24/05/2012 9:44:59 High Impact Research Annual Report 2011 48. Zak AK, Gan WC, Abd. Majid WH, Darroudi M, Velayutham TS. Experimental and Theoretical Dielectric Studies of PVDF/PZT Nanocomposite ThinFilms.CeramInt.2011;37:1653-60. 54. NguiR,IshakS,ChuenCS,MahmudR,LianYLA. Prevalenceandriskfactorsofintestinalparasitism in rural and remote West Malaysia. 2011; PLoS NTD5(3):e974. 49. Zak AK, Razli R, Abd. Majid WH, Darroudi M. Synthesis and characterization of narrow size distribution of zinc oxide nanoparticles. Int J Nanomed.2011;6:1399–1403. 55. Ngui R, Lim YAL, Amir NF, Nissapatorn V, Mahmud R 2011. Seroprevalence and sources oftoxoplasmosisamongOrangAsli(Indigenous) Communities in Peninsular Malaysia. American Journal of Tropical Medicine and Hygiene 2011; 85:660-666. 50. Zak AK, Yousefi R, Abd. Majid WH, Muhamad MR.FacilesynthesisandX-raypeckbroadening studiesofZn1-xMgxOnanoparticles.CeramInt.. doi:10.1016/j.ceramint.2011.10.042 (Article in press). 51. Razali R, Zak AK, Abd. Majid WH, Darroudi M. Solvothermal synthesis of microsphere ZnO nanostructures in DEA media. Ceram Int. 2011; 37:3657-63. 52. VelayuthamTS,AbdMajidWH,AhmadAB,Gan SN. Electrical behaviour of polyurethane derived from polyols synthesized with glycerol, phthalic anhydrideandoleicacid.JApplPolymSci.2011; 121:1796-1803. 143 56. Ngui R, Ching LS, Kai TT, Roslan MA, Lim YAL. Molecular identification of hookworm infections inruralandremoteareasofPeninsularMalaysia. American Journal of Tropical Medicine and Hygiene2011.(Acceptedforpublication). 57. OoiR.ConversionofheattolightusingTownes’ maser-laser engine: Quantum optics and thermodynamic analysis. Physical Review 2011; A 83;043838. 58. Ooi R. Near-Field and Particle Size Effects in Nonlinear Optical Scattering. PIERS 2011; 117: 479. 53. Hany A. Childhood Adrenal Cortical Carcinoma as a Sentinel Cancer for Detecting Families with Germline TP53 Mutations, Clinical Genetics (acceptedforpublication). HIR Annual report 2011.indb 143 24/05/2012 9:44:59 144 High Impact Research Annual Report 2011 HIR PAPER PRESENTATION 1. Aziz N, Yusoff R, Aroua MK. CO2 Absorption UsingMixturesofIonicLiquidandAlkanolamines 3rd International Congress on Green Process Engineering, 6-8 December 201, Seri Pacific Hotel,KualaLumpur,Malaysia.Abstractno163, pp.73. 2. Ngeow YF. Molecular characterization of MDRTB strains in Malaysia. 1st AMDI International Biohealth Science Conference,29 Nov-1 Dec, 2010,Penang. 3. Mei YS, Ling NS, Peng NK. Molecular approach in characterization of Cladosporium isolates. In Symposium on leveraging on microbial diversity for a sustainable future, Bayview Beach resort, Penang, 8th – 11th December 2011. Poster presentation. 4. GopalK,AmirhamedH,KamarulT.Uniaxialtensile loadinginfluencescellproliferationandapoptosis inadultbonemarrowderivedMesenchymalstem cells. 41st Malaysian Orthopaedic association annual scientific meeting. 22nd – 24th May 2011, Kuala Lumpur Convention Centre. Abstract No.P016,pp140. 5. KufianMZ,YusufSNF,MajidSR,ArofAK.PMMALiBOB Gel Electrolyte for lithium Ion Batteries, Posterpresentation,XIIInternationalSymposium onPolymerElectrolytes,29August-3September 2010Padova,Italy. 6. Samin SM, Md. Isa KB, Othman L, Osman Z. “Li-IonconductionandStructuralStudiesofGPE basedonPolymethymethacrylate”,presentedat Malaysia Polymer International Conference, 18 – 20 Oct 2011, Bangi, Selangor, (selected to be publishedinJurnalSainsMalaysiana). 7. Ghazali MIM, Othman L, Md Isa KB, Osman Z. “Ionic Conductivity and Structural Studies of PMMA+EC+PC+LiBF4GelPolymerElectrolytes”, presented at Malaysia Polymer International Conference, 18 – 20 Oct 2011, Bangi, Selangor, (selected to be published in Jurnal Sains Malaysiana). 8. 9. MdIsaKB,OthmanL,MansorM,OsmanZ.“Ionic Conductivity And Transference Number Studies of PVDF-HFP/PMMA – (EC+PC) Gel Polymer Electrolytes Containing Lithium Salt”, presented atMalaysiaPolymerInternationalConference,18 – 20 Oct 2011, Bangi, Selangor, (selected to be publishedinJurnalSainsMalaysiana). 11. Vincent-Chong VK, Rahman ZAA, Ismail SM, Zakaria Z, Pradeep PJ, Kallarakkal TG, Ramanathan A, Karen-Ng LP, Tay KK, Zain RB. Recurrent amplicon of nestin and its mRNA expression in oral squamous cell carcinoma (OSCC). 4th Regional Conference on Molecular Medicine (RCMM), 9-11 October 2011, G-Hotel, Penang,Malaysia.Abstractno.OP13;pp37. 12. Kong YH, Syed Zanaruddin SN, Ghani WMN, RahmanZAA,AbrahamMT,RamanathanA,Lau SH, Zain RB, Cheong SC. Expression of EMT markersisassociatedwithpatternofinvasionin oralcancer.4thRegionalConferenceonMolecular Medicine,(RCMM),9-11October2011,G-Hotel, Penang, Malaysia. Abstract no. OP11; pp35 (AwardedtheBestOralPresentation). 13. Dambul KD, Tamchek N, Sandoghchi SR, Abu Hassan MR, Tee DC, Mahamd Adikan FR. ‘Fabrication and Characterization of Flat Fibers’, 2ndInternationalConferenceonPhotonics2011 (ICP2011),Sabah,Malaysia,pp.27-30,October 2011. 14. JahanshahiP,SandoghchiSR,ParviziA,Mahamd Adikan FR. “Three-dimensional Modeling of Surface Plasmon Resonance Based Biosensor”, COMSOL Conference 2011 Boston, Boston, Massachusetts02466,USA. 15. ChanSY,SamIC,ChanYF.DifferentialProteome analysis of human colon adenocarcinoma cells infected with enterovirus 71 and coxsackievirus A16. 1st International Symposium of Infectious DiseasesandSignalTransductionResearch.1920November2011,Tainan,Taiwan. 16. Tan CW, Chan YF, Tan EL, Sim KM, Poh CL. Inhibition of enterovirus 71 infections by a novel peptidederivedfromenterovirus71capsidprotein VP1. 1st International Symposium of Infectious DiseasesandSignalTransductionResearch.1920November2011,Tainan,Taiwan. 17. Chan YF. Enterovirus 71: a decade later. 9th Biennial Convention of the Asean Neurological Associaiton (ASNA): Neuroinfection symposium. 2-5November,2011. 18. Chan YF. Phylogenetic designation of EV71 genotypes and subgenotypes. The 1st InternationalSymposiumofVaccineDevelopment againstHumanHand-Foot-and-MouthDiseases. 4-5September2011,Zhunan,Taiwan. Othman L, Samin SM, Zainol NH Md Isa KB, OsmanZ.“LithiumIonConductionStudiesofGel PolymerElectrolytesBasedonPMMA”,presented atMalaysiaPolymerInternationalConference,18 –20Oct2011,Bangi,Selangor. 19. Sam IC. The burden of infectious diseases in Southeast Asia. Microsystems Technologies for African Health, μ-Med-A 2011, 7-9 September 2011, Protea Hotel, Kruger Gate, Mpumalanga, SouthAfrica. 10. Osman Z, Zulkifli MF, Md Isa KB, Othman L. “PreparationandCharacterizationofGelPolymer ElectrolytesBasedonPVDF-HFP/PMMABlend”, presented at Malaysia Polymer International Conference,18–20Oct2011,Bangi,Selangor. 20. ChiamCW,ChanYF,OngKC,WongKT,SamIC. NeurovirulencevariationofdifferentChikungunya virus genotypes in ICR suckling mice. 16th Biological Sciences Graduate Congress, 12-13 December 2011, National University Singapore, Singapore. HIR Annual report 2011.indb 144 24/05/2012 9:44:59 High Impact Research Annual Report 2011 21. FreemanMA,HorákA,EydalM,KeelingP.X-cell parasitesofAtlanticcodarebasaldinoflagellates. VI European Congress of Protistology (ECOP VI). 25th-29th July 2011 Freie Universität Berlin, Germany.OralAbstractpp64. 22. Chan KG, Chong TM., Sam SC, Koh CL. SalD, a lactonase in Staphylococcus sp. L1, and its predicted homologues. 4th ASM Conference on Cell-CellCommunicationinBacteria.6-9Nov 2011.Miami,USA.56:25. 23. Soh Y, Chhabra SR, Halliday N, Williams P, Chan KG. Inactivation of the Pseudomonas aeruginosa quinolone signal molecule, PQS by Achromobacter xylosoxidans. 6-9 Nov 2011. Miami,USA.56:26. 24. Lee IL,Suresh K. Blastocystis spp: Evidence of its occurrence in water sources in Peninsular Malaysia. Oral presentation at the 47th Annual Scientific Seminar of Malaysian Soceity of ParasitologyandTropicalMedicineatInstituteof MedicalUniversity3rd -4th March2011. 25. Afzan MY, Suresh K. Phenotypic and genotypic characterization of Trichomonas vaginalis. Oral presentation at the 47th Annual Scientific Seminar of Malaysian Society of Parasitology and Tropical Medicine at Institute of Medical University3rd -4th March2011. 26. Ronald VS, Abdullah AN, Govindasamy V, Musa S,AbuKasimNH.HumanDentalStemCellsand TheirPlasticityPotentials.JDentRes90B,(www. dentalresearch.org)(ISI-CitedAbstract) (ISI-Cited Publication) IADR Singapore, SEA 28th- 30th October2011. 27. Abdullah AN, Ronald VS, Govindasamy V, Musa S, Abu Kasim NH. Dental Pulp Stem Cells : Hepatocyte Differentiation in Animal-free Serum. J Dent Res 90B, (www.dentalresearch.org) (ISI- Cited Abstract) (ISI-Cited Publication) IADR Singapore,SEA28th-30thOctober2011. 28. TiekinkERT.Crystal Engineering: Steric Bulk as a Design Element - Implications for Luminescence and Nanoparticle Generation. Departmental Seminar,April26th2011,DepartmentofChemistry. UniversitiBruneiDarussalem. 29. Tiekink ERT. Emerging supramolecular syntrons: Stabilisation of crystal structures by C.H… pi(chelate ring) and by metal(lone pair)…pi(aryl) interactions.DepartmentalSeminar,October13th 2011, Department of Chemistry. University of Malaya. 30. Tiekink ERT. Emerging supramolecular syntrons: Stabilisation of crystal structures by C.H… pi(chelate ring) and by metal(lone pair)…pi(aryl) interactions. Keynote Speaker, October 17th 2011, 3rd Asian Conference on Coordination Chemistry(ACCC-3). 145 32. YeoGN,WoonKL.InfluenceofSeriesResistance, ShuntResistanceandInterfacePropertiesonFill FactorofP3HT/PCBMOrganicPhotovoltaic-26th RegionalConferenceonSolidStateScienceand Technology 2011, 22-24 November 2011, The Royale Bintang Seremban, Negeri Sembilan, Malaysia.RCSSSTAbstractnoC10. 33. Abdullah Norbani, Mohammad Isa Mohamadin Mixed-Valence Low Bandgap Photovoltaic Material: [Cu(II)Cu(I)(R)3(RH)2CH3COCH3 (R = C6H5COO; L =CH3COCH2C(OH)(CH3)2) 2011 InternationalConferenceonEnergy,Environment andSustainableDevelopment. 34. A.K. Zak, W.H. Abd. Majid, W. C. Gan, “Experimental and Theoretical Dielectric Studies of PVDF/PZT Nanocomposite Thin Films”, International Symposium on Advanced Materials forOpticsMicroelectronicsandNanaoelectronics, AMOMEN’2011, Kénitra Morocco, 27-29 Oct. 2011-InvitedSpeaker. 35. RehanaRazali,W.Abd.Majidetal,“Solvothermal synthesis of microsphere ZnO nanostructures in DEA media”, International Symposium on Advanced Materials for Optics Microelectronics and Nanaoelectronics, AMOMEN’2011, Kénitra Morocco,27-29Oct.2011-PosterPresentation. 36. Soo Sin CHOONG, Zarina Adbul LATIFF, Mahfuzah MOHAMED, Leon Li Wen LIM, Kok SiongCHEN,LelamekalaVENGIDASAN,Hadibiah RAZALI, Eni Juraida ABDUL RAHMAN, Hany ARIFFIN,Childhood Adrenocortical Carcinoma as a Sentinel Cancer of Li-Fraumeni Syndrome. 16th Biological Sciences Graduate Congress, 12nd -14th December 2011, National University ofSingapore,Singapore. 37. Choo, Y. M. “Malaysian Terrestrial Plants and Microorganisms: Source of New Leads”, The 6th International Conference on Cutting-Edge OrganicChemistryinAsia11-15December2011 Hong Kong. Invited oral presentation. Abstract No.IL-8. 38. RomanoNgui,YvonneA.L.Lim,RebeccaTraub, Rohela Mahmud, Mohd Sani Mistam. Zoonotic transmission of Ancylostoma ceylanicum among humananddomesticanimalsinendemicareasof Malaysia. JITMM 2011. December 1-2, Centara Grand & Bangkok Convention Centre, Central World,Bangkok,Thailand. 39. “Superconducting Photonic Crystal with Nanostrips for Mid-Infrared Applications”, Ooi C. H. Raymond, Malaysia Annual Physics Conference2010(PERFIK-2010):AIPConference ProceedingsVolume:1328Pages:24-27(2011). 31. LimCH,ChanCS.AFrameworkonFuzzyIntrusion Detection.IWACIII,Suzhou,China.2011. HIR Annual report 2011.indb 145 24/05/2012 9:44:59 146 High Impact Research Annual Report 2011 HIR GUIDELINES Introduction The high impact research grants from the University ofMalayaaretofundprojectswhichwillresultinthe publicationofmanuscriptsinTier1ISI/WebofScience journals.Assuch,theemphasiswillbeonfundamental research which will lead to the generation of new knowledge rather than on the development of new productsorpatents.Itisalsoaimedatgeneratingmore researchcapabilitiesandexpertisewithintheuniversity andthismayresultfromcollaborationwithIvyLeague universitiesoverseas. Thesegrantswillbehandleddifferentlyfromallexisting grantsandwillbeadministeredundertheChancellery. The Vice-Chancellor will be Chairman of the High Impact Research Committee which will evaluate the projects, decide on its suitability for funding and monitortheirprogress. Each project initial funding will have a ceiling of RM500,000 over 2 years, but those which receive more funding will be expected to out-perform those withlessfunding.Theinitialfundingwillbefor2years with the proviso that projects with excellent outcome will receive further funding. To make projects more cost-effective, each Tier 1 paper should not exceed RM60,000.Projectsrequestingformorethan40%of totalbudgetforequipmentwillnotbeconsidered. • Allocation cannot be used for study fees. The maximum wages/allowances for temporary or contract personnel will be based on prevailing rates. TravelandTransportation(V21000) Includes travel and transportation expenses for domesticandoverseastripswhicharedirectlyrelated totheproject. Overseastripsmustmeetthefollowingcriteria: • Attendingconferences,seminarsorworkshopsto presenttheresultsoftheproject. • Conducting a portion of the required research when domestic facilities and expertise are inadequate. • Thevenuefortheabovemustbesuitableinterms offacilities,expertiseandtechnologytransfer. • Travel is limited to economy class using the shortest direct routes. Travel is only allowed on MASorAirAsiacarriersexceptunderextenuating circumstances. Rentals(V24000) All projects must have international partnerships. Each PI will have only 1 HIR funded project under the Chancellory HIR Fund. Those who are about to complete their current project and have met their targetsmaybeconsideredforasecondgrant. • Eligibility ResearchMaterialsandSupplies (V27000) All academic staff, senior research fellows, research fellows,andexpatriatesattachedtotheuniversityare eligibletoapply. Post-doctoral researchers must apply in the name of theirsupervisorsoramemberoftheacademicstaff. ScopeofFunding Only projects which will result in Tier 1 ISI/Web of Science publications will be funded. Successful PIs will need to sign a contract to agree to the terms of funding. Thefundingcanbeutilizedforthefollowingcategories: • Only rental expenses for building space, equipment, transportation and any other items directlyrelatedtotheprojectshouldbeincluded. Rentalofvehiclesforthepurposeoftransportation mustbefromalicensedtransportcompany. Onlyexpensesforresearchmaterialsandsupplies directlyrelatedtotheprojectshouldbeincluded. MinorModificationsandRepairs (V28000) • Onlyexpensesforminormodificationsandrepairs of the laboratory, equipment or any other items directlyrelatedtotheprojectshouldbeincluded. • The maintenance costs of existing equipment usedduringthedurationofprojectperiodshould alsobeincluded. WagesandAllowancesforTemporaryand ContractPersonnel(V11000) • Includes wages and allowances for temporary andcontractpersonnelwhoaredirectlyengaged intheproject. HIR Annual report 2011.indb 146 24/05/2012 9:45:00 High Impact Research Annual Report 2011 SpecialServices(V29000) PUBLICATIONS • Services directly related to the project such as consultancy, payment for enumerators, usage of computer facilities, chemical analysis, data processingandpatentregistration. Researchersshouldonlypublishtheirresearchfindings in Tier 1 ISI/Web of Science journals. All publications must indicate and acknowledge the University of Malayaasthesourceoffunding. • Engagementofforeignexpert(s)willbeconsidered onacase-bycasebasis. ThePImustindicateintheapplicationformthenumber ofTier1publicationsexpectedfromtheproject,aswell as a list of five Tier 1 journals which the publications willappearin. EquipmentandAccessories(V35000) • • Special equipment and accessories purchased, includingaccessoriestoupgradethecapabilityof existingequipmentdirectlyrelatedtotheproject. Funding for special equipment and accessories has to be reasonable and should have a direct bearingontheproject. VariationsinProjectCosting Requests for variations in funding after a project has been approved must be made to the Committee for approval. ProjectExtension Requestsforprojectextensionsmustbemadetothe Committee6monthsbeforethecompletiondateofthe project. The maximum extension period is not more than6months. AcceptanceofOffer Applicants must accept or decline the offer within 14 days after notification. Upon acceptance, the PI will needtosignacontractwiththeuniversitytofulfillall thetermsandconditionsasstated. OwnershipofResearchEquipment All research equipment purchased under the project belongstotheuniversityandshouldbemadeavailable tootherresearchers.Theuniversityreservestheright tore-locatetheequipmentattheendoftheproject. 147 FINANCIALREPORT AFinancialreportmustbesubmittedatthesametime astheprogressreport. PROJECTIMPLEMENTATIONAND MONITORING • PROJECTIMPLEMENTATION AllprojectsfundedbytheHighImpactResearchGrant must be conducted in accordance withtherulesand conditions governed by research in the university. Projects which involve experimentation with humans or animals will require approval from the respective Ethics Committees prior to the fund being released. The projects will be closely monitored to ensure that theyarecarriedoutsuccessfully. • PROGRESSREPORT(PR) 1. Thefirstprogressreportmustbesubmitted 8monthsafterthebeginningoftheproject. Thesecondreportshouldbe16monthsafter theprojecthasstarted. 2. FailuretosubmittheProgressReportbythe stipulateddatelinesmayresultinsuspension oftheprogresspayments. 3. The End of Project Report (EPR) is to be submitted3monthsafterthecompletionof theproject 4. In addition to reviewing the above reports, the Committee may, from time to time, conduct on-site monitoring of projects and colloquiums. Note: Failure to complete the project satisfactorily mayresultintheresearcherbeingbarredfrommaking futureapplicationsforuniversityresearchfunding. HIR Annual report 2011.indb 147 24/05/2012 9:45:00 148 High Impact Research Annual Report 2011 SOP FOR THE MANAGEMENT OF HIR FUND (AFTER APPROVAL BY HIR COMMITTEE) 1. Received approval letter, account number and SOPforHIRFundManagement. 2. ResearchAssistant (Master) RM2,500-RM4,000 Spending should start immediately according to thefollowingfinanciallimits:- ResearchAssistant (Degree) RM1,200-RM2,500 (Please state the documentation) ProjectAssistant(SPM/ Diploma) RM800-RM1,500 account number in all a) b) ForpurchaseofitemsbelowRM5,000 ForpurchaseofitemsmorethanRM5,000 toRM20,000 c) ForpurchaseofitemsmorethanRM20,000 toRM50,000 d) ForpurchaseofitemsmorethanRM50,000 toRM100,000 e) Forpurchaseofitemsmorethan RM100,000toRM500,000 f) Forpurchaseofitemsmorethan RM500,000 All expenses must be made according to approved allocation by each vote. 3. 5. RecruitmentProcess: i. PItoforwardallrelevantdocumentsforeach candidatetotheHIRSecretariat: 1. Application form with passport size photograph 2. (Can be downloaded from http://www. hir.um.edu.my) 3. 1 copy of RA’s Bank account number (CIMBonly-forsalarycrediting) 4. 1 copy of passport front page (foreignersonly) Any transfer between the votes needs the VC’s approval. ii. Allappointmentof RAs will be submitted to HIR Secretariat. Monthly salary offered will be based onthesalaryrangeaccordingtoRAqualification andexperienceasfollows: HIRSecretariatwillprocessandissueLetter of Appointment to RA; copies to PI, Bursar andHumanResourceDepartment. iii. UponstartofdutyPItoforwardReportDuty ofthecandidatestotheHIRSecretariatand copytoBursar’sOfficetoinitiatepaymentof salaries. SeniorResearcher(PhD& 5yearsexperience RM5,000-RM7,000 HIRPost-Doc(PhD) RM4,000-RM6,000 4. PIreceivesexpensereportsfromBursar’sOffice– Reconcileandconfirm. ContactPerson: VC’sOffice SitiZawahirZubir 03-79673400 zawahirzubir@gmail.com VC’sOffice AzbullahCheIbrahim 03-79673231 azbullahibrahim@gmail.com VC’sOffice NurAinValerieCasseraBintiRapoi 03-79677763 navalcas@um.edu.my VC’sOffice HamizahHusain 03-79677791 hamizah_husain@um.edu.my VC’sOffice SarinaRamli 03-79677790 rienaramli@um.edu.my Bursar HalizaHarun 03-79673205 halizahr@um.edu.my AssistantBursar NorshahidayuAli 03-79673270 shahidayu@um.edu.my ProcurementUnit PuteriHeirzereinMegatZamry 03-79676996 put3mz@um.edu.my PaymentUnit Dr.NoorHashimTaib 03-79673403 nhashim@um.edu.my FacultyofMedicine SitiFatimahZahraMohdAnuar 03-79677515 fatimah_zahra@ummc.edu.my FacultyofEngineering NoorlainiewatiAbdullah 03-79677684 laini@um.edu.my FacultyofScience AzianAwang 03-79674201 azianawang@um.edu.my FacultyofDentistry IntanSuhanaHamid 03-79676454 intansuhana@um.edu.my FacultyofComputerScience &InformationTechnology MuhamadAfiqZainiAlamar 03-79676382 afiq.almar@um.edu.my Secretariat, HighImpactResearchGrant OfficeoftheViceChancellor Level9,ChancelloryUniversityofMalaya 50603KualaLumpur hirgrant@gmail.com http://www.hir.um.edu.my HIR Annual report 2011.indb 148 24/05/2012 9:45:00 High Impact Research Annual Report 2011 HIR Annual report 2011.indb 149 149 24/05/2012 9:45:00 150 High Impact Research Annual Report 2011 GUIDELINES ON TECHNICAL EVALUATION 1. Doestheprojectmeettheexpectationsofthe HIRGrantScheme? TheHIRGrantSchemefromtheUniversityofMalaya is to fund projects which will result in publications in Tier 1/ISI WoS journals. As such, the emphasis is on fundamentalresearchwhichwillleadtothegeneration ofnewknowledgeratherthanonthedevelopmentof newproductsorpatents. 2. DothePrincipalInvestigator(PI)andthe researchteamhavetheexpertiseand thenecessarytrackrecordinconducting researchinthisarea? Itisimportanttolookattheprofessionalqualifications andpastperformanceofthePIandhisteam.Weshould refer to the records of the researchers with regard to the type of projects funded, whether completed or on-going and the outcome of those funded projects. TheCVsofthePIandhiscollaboratorswillbeagood indicatoroftheirrecordsandpreviousexperiences. The budget should reflect on this collaboration, with exchangesofvisitsbetweenthecollaboratingcentres. Prominent Malaysian scientists working overseas should be invited to participate in HIR projects and funds provided to encourage them to be actively involved. There should be documentary evidence to show that the collaboration is active and meaningful andwillleadtoanoutcomeofmutualbenefit. 7. AppropriatenessofResearchMethodology Theresearchmethodologyintheapplicationformmust containsufficientinformationfortheHIRCommitteeto determinethefeasibilityoftheproject.FlowandGrant charts of research activities must be provided and the respective milestones and dates of achievements provided. These will serve for the monitoring of the projectoutcomes. 8. ResearchBudget Inordertoavoidduplication,wemustensurethatthe HIR project has not been funded elsewhere. There shouldbeasubstantialdifferencebetweenthisproject andthosepreviouslyconductedbytheresearchers. Thebudgetrequestshouldberealisticandreflectthe targetandcost-benefitsoftheproject.Theguidelines fortheutilizationofHIRbudgetshouldgenerallybein linewiththeguidelinesassetupbyothergovernment ministriessuchasMOSTIandMoHE.However,more flexibility will be allowed here subject to the approval oftheVice-ChancellorwhoistheChairmanoftheHIR Committee(refertoScopeofFundingintheGuidelines forHighImpactResearchGrants). 4. Creditabilityofresearchobjectives 9. Cost-effectivenessofHIRProjects The research objectives must be clear, accurate and consistent and the proposed methodology relevant to meet the set goals. It is important to ensure the objectives are not too ambitious and that the goals are achievable within the time period set. Objectives mustbesetinsuchawaythattheyareverifiableupon completionoftheproject. The cost-effectiveness of the HIR project should be relatedtothebudgetrequestandthenumberofTier 1 publications. If the merits of two proposals are the same,thenitisobviousthattheonewithbettercostbenefitswillbegivenpriority.Asaruleofthumb,under theSAGAResearchProgrammeofMOSTIunderRMK 8,thecost-benefitsofSAGAprojectsaveragetoabout RM46,000perISIpublication.Requestsforequipment must be related to the project and must be justified. Althoughthereisnocapontherequestforequipment budgetvis-à-visthetotalbudget,thegeneralpractice withgovernmentfundinghasbeen40%oftotalbudget forequipment. 3. Whatotherfundingsourceshavebeen awardedpreviously? 5. Outputexpected The primary output expected of HIR funded projects areTier1ISI/WoSpublicationsandanyotheroutcome issecondary.AlistofTier1journalsshouldbeprovided by the PI and the number of expected publications mustreflectthecost-benefitoftheprojectoutputand budgetrequest. 6. ResearchCollaboration Research collaboration is strongly encouraged and emphasis should be placed on international collaboration with Ivy League universities and institutions that can lead to the transfer of cuttingedgetechnologiesandthetrainingofUMresearchers. HIR Annual report 2011.indb 150 10. HIRRecommendationsfollowingTechnical Review HIR Committee Members should convey to the PI the reasons that their recommendation to projects that have been rejected. PIs are then advised to look for funding elsewhere (MOSTI RMK10, MoHE or FRGS). Projects which require large budgets may be considered under the category “Commissioned Research”andtheprojectsubjectedtomorestringent evaluationandthePIinterviewed. 24/05/2012 9:45:00