scieee AI-readable full text Open interactive document viewer

Glycerol valorisation as biofuel: Glycerol acetals production by Simulated Moving Bed Reactor

Rui Pedro Vieira Faria

Full text

    )DFXOGDGHGH(QJHQKDULDGD8QLYHUVLGDGHGR3RUWR  *O\FHUROYDORULVDWLRQDVELRIXHOV *O\FHURODFHWDOVSURGXFWLRQE\6LPXODWHG0RYLQJ %HG5HDFWRU 'LVVHUWDWLRQ3UHVHQWHGWR)DFXOGDGHGH(QJHQKDULDGD8QLYHUVLGDGHGR3RUWRIRUWKH GHJUHHRI3K'LQ&KHPLFDODQG%LRORJLFDO(QJLQHHULQJ  E\ 5XL3HGUR9LHLUD)DULD 6XSHUYLVRU3URI'U$OtULR(5RGULJXHV &RVXSHUYLVRU'U&DUOD603HUHLUD    /DERUDWRU\RI6HSDUDWLRQDQG5HDFWLRQ(QJLQHHULQJ$VVRFLDWH/DERUDWRU\/65(/&0 'HSDUWPHQWRI&KHPLFDO(QJLQHHULQJ)DFXOW\RI(QJLQHHULQJ8QLYHUVLW\RI3RUWR                                                )(83/65(/&08QLYHUVLGDGHGR3RUWR 5XL3HGUR9LHLUD)DULD $OOULJKWVUHVHUYHG   $FNQRZOHGJPHQWV )LUVW DQGIRUHPRVW,ZLVK WRWKDQNWR P\VXSHUYLVRU3URIHVVRU$OtULR5RGULJXHVIRUKLV YDOXDEOH DGYLFHV DQG LQVLJKWV ,W LV UHDOO\ D SOHDVXUH WR ZRUN ZLWK VRPHRQH ZLWK VR PXFK NQRZOHGJHWRVKDUH ,DOVRRZHP\GHHSHVWJUDWLWXGHWR'U&DUOD3HUHLUDP\FRVXSHUYLVRUZKRGHYRWHGVR PXFKRIKHUSUHFLRXVWLPHDQGDWWHQWLRQZKHQHYHU,UHTXHVWHG,WZDVIRUVXUHWKDWNLQGRI GHGLFDWLRQ DQG FRPPLWPHQW WKDW PDGH KHU VXFK D UHPDUNDEOH SURIHVVLRQDO« DQG DQ H[WUDRUGLQDU\SHUVRQ 7KHUHVHDUFKOHDGLQJWRWKHUHVXOWVSUHVHQWHGLQWKLV7KHVLVZRXOGQRWEHSRVVLEOHZLWKRXW WKH ILQDQFLDO VXSSRUW IURP WKH (XURSHDQ 8QLRQ 6HYHQWK )UDPHZRUN 3URJUDPPH )3 XQGHU*UDQW$JUHHPHQW(XUR%LR5HI 7KH UHOHYDQW FRQWULEXWLRQV RI 'U 9LYLDQD 6LOYD DQG 3URIHVVRU -RVp 0LJXHO /RXUHLUR HVSHFLDOO\DWWKHHDUOLHUVWDJHVRIP\3K'FDQQRWEHIRUJRWWHQDVZHOO ,ZRXOGDOVROLNHWRWKDQNDOOP\3URIHVVRUVDQGFROOHDJXHVDWWKH/65(IRUWKHLUNLQGQHVV DQG VXSSRUW , IHHO YHU\ IRUWXQDWH IRU EHLQJ D SDUW RI VXFK D TXDOLILHG DQG SURIHVVLRQDO UHVHDUFKWHDP ,WLVZLWKLPPHQVHJUDWLWXGHWKDW,DFNQRZOHGJHWKHKHOSRIP\IHOORZODEPDWHV'kQLD &RQVWDQWLQR DQG %UXQR 6DQWRV :RUNLQJ WRJHWKHU RYHU WKH ODVW WKUHH \HDUV ZDV D YHU\ HQULFKLQJH[SHULPHQWERWKSHUVRQDOO\DQGLQWHOOHFWXDOO\ 7RDOOP\ORQJWLPHIULHQGVWKDQN\RXIRUDOOWKHPRPHQWVRIUHOD[DWLRQDQGIXQWKDWZH KDYHVKDUHG/LIHVHHPVHDVLHUZKHQ\RXDUHDURXQG , FDQQRW ILQG ZRUGV WR H[SUHVV P\ JUDWLWXGH WR P\ 3DUHQWV DQG P\ 6LVWHU 7KHLU XQFRQGLWLRQDO ORYH DQG VXSSRUW HQFRXUDJHG PH LQ HYHU\ PRPHQW RI P\ OLIH , RZH WKHP HYHU\WKLQJ,DPWRGD\ )LQDOO\DQGPRVWLPSRUWDQWO\,DPSURIRXQGO\JUDWHIXOWRP\:LIH-RDQDIRUKHUORYH WHQGHUQHVVSDWLHQFHDQGXQGHUVWDQGLQJ7KDQN\RXIRUDOO\RXDUHLQP\OLIH      5HVXPR 2SULQFLSDOREMHWLYRGDLQYHVWLJDomRGHVHQYROYLGDDRORQJRGRSUHVHQWHSURJUDPDGRXWRUDO IRL D YDORUL]DomR GR JOLFHURO REWLGR FRPR H[FHGHQWH GXUDQWH R SURFHVVR GH SURGXomR GH ELRGLHVHO DWUDYpV GD VXD WUDQVIRUPDomR HP DFHWDO HWtOLFR GH JOLFHURO *($ UHFRUUHQGR DR UHDWRU GH OHLWR PyYHO VLPXODGR FRPR HVWUDWpJLD GH LQWHQVLILFDomR GH SURFHVVRV WHQGR HP YLVWDDLPSOHPHQWDomRGHXPSURFHVVRLQGXVWULDOHILFLHQWHHVXVWHQWiYHO3DUDHVWHHIHLWRIRL QHFHVViULD D VHOHomR GH XP FDWDOLVDGRUDGVRUYHQWH DGHTXDGR H D REWHQomR GH GDGRV IXQGDPHQWDLV GD FLQpWLFD GD UHDomR TXtPLFD GH VtQWHVH GR UHIHULGR DFHWDO H GH GDGRV GH DGVRUomRGHWRGRVRVFRPSRVWRVGHVWHVLVWHPDUHDFLRQDOXVDQGRRVyOLGRHVFROKLGR 1XPD SULPHLUD IDVH IRL HODERUDGR XP HVWXGR HQYROYHQGR WHVWHV FLQpWLFRV D  FDWDOLVDGRUHVGLVSRQtYHLVFRPHUFLDOPHQWH]HyOLWRVHUHVLQDVGHSHUPXWDLyQLFDWHQGRVLGR VHOHFLRQDGDDUHVLQDGHSHUPXWDLyQLFD$PEHUO\VWZHW3URFHGHXVHDRHVWXGRGHWDOKDGR GD UHDomR HQWUH JOLFHURO H DFHWDOGHtGR QXP UHDWRU IHFKDGR GHWHUPLQDQGR RV SULQFLSDLV SDUkPHWURV GH HTXLOtEULR WHUPRGLQkPLFR H FLQpWLFRV WHQGR VLGR SURSRVWR R PRGHOR GH /DQJPXLU+LQVKHOZRRG+RXJHQ:DWVRQ SDUD D OHL GH YHORFLGDGHV 6HJXLGDPHQWH IRL GHVHQYROYLGD XPD PHWRGRORJLD SDUD D HVFROKD GH VROYHQWHV SDUD SURFHVVRV LQWHJUDGRV GH UHDomRDGVRUomR$DSOLFDomRGHVWDPHWRGRORJLDDRVLVWHPDHPHVWXGRSHUPLWLXLGHQWLILFDUR GLPHWLO VXOIy[LGR FRPR R VROYHQWH PDLV DSURSULDGR WHQGRVH DQDOLVDGR R LPSDFWR GD LQWURGXomRGHVWDHVSpFLHQRPHLRUHDFLRQDO 'DGRV UHODWLYRV DR HTXLOtEULR GH DGVRUomR IRUDP REWLGRV DWUDYpV GH WHVWHV QXPD FROXQD FURPDWRJUiILFD UHFRUUHQGR D XPD PHWRGRORJLD GH DQiOLVH IURQWDO H RV UHVXOWDGRV IRUDP DMXVWDGRVDXPDLVRWpUPLFDGH/DQJPXLUPXOWLFRPSRQHQWH $HVWUDWpJLDGHLQWHQVLILFDomRGHSURFHVVRVDGRWDGDEDVHDGDQDLQWHJUDomRGHSURFHVVRV GHDGVRUomRHUHDomRSHUPLWLXHIHWXDUDVtQWHVHGH*($QXPUHDWRUFURPDWRJUiILFRFRQWtQXR GHOHLWRIL[R $WUDYpV GD UHDOL]DomR GH HQVDLRV H[SHULPHQWDLV QXP UHDWRU GH OHLWR PyYHO VLPXODGR j HVFDODSLORWRGHPRQVWURXVHTXHDSURGXomRGH*($DWUDYpVGHVWDWHFQRORJLDpSRVVtYHO 0RGHORV PDWHPiWLFRV FRPSOH[RV FRQWHPSODQGR IHQyPHQRV GH WUDQVIHUrQFLD GH PDVVD UHDomR H DGVRUomR IRUDP GHVHQYROYLGRV SDUD FDGD XPD GDV WHFQRORJLDV DQWHULRUPHQWH UHIHULGDV UHDWRU IHFKDGR UHDWRU FURPDWRJUiILFR GH OHLWR IL[R H UHDWRU GH OHLWR PyYHO VLPXODGRSHUPLWLQGRQmRVyDSURIXQGDURFRQKHFLPHQWRDFHUFDGHFDGDXPGHVWHVSURFHVVRV PDVWDPEpPSURFHGHUjRWLPL]DomRGDVVXDVFRQGLo}HVGHRSHUDomR      Y  /LVWRI)LJXUHV )LJXUH²:RUOGUHJLVWHUHGDQGSUHGLFWHGHQHUJ\FRQVXPSWLRQEHWZHHQDQG    )LJXUH&RQYHQWLRQDOJO\FHURODSSOLFDWLRQVDGDSWHG    )LJXUH²*O\FHUROJOREDOSURGXFWLRQDQGSULFHVHYROXWLRQDGDSWHG    )LJXUH²*($PHPEHUHGULQJLVRPHUDDQGFDQGPHPEHUHGULQJLVRPHUE DQGG  )LJXUH²6FKHPHIRUWKHUHDFWLRQPHFKDQLVPRIWKHFRQGHQVDWLRQRIJO\FHUROZLWK DFHWDOGHK\GH    )LJXUH²)ORZVKHHWIRUWKHFRQWLQXRXVSURGXFWLRQRIELRGLHVHOFRQWDLQLQJDJO\FHURO DFHWDODGGLWLYHREWDLQHGE\DQDFHWDOL]DWLRQUHDFWLRQDGDSWHG    )LJXUH²)ORZVKHHWIRUWKHFRQWLQXRXVSURGXFWLRQRIELRGLHVHOFRQWDLQLQJDJO\FHURO DFHWDODGGLWLYHREWDLQHGE\WUDQVDFHWDOL]DWLRQUHDFWLRQDGDSWHG    )LJXUH²*($LVRPHUVLQWHUFRQYHUVLRQLQWKHSUHVHQFHù   − ⋅  PRO GP RI SHUFKORULFDFLGLQEHQ]HQHDW . DGDSWHG    )LJXUH²,VRPHUVUDWLRHYROXWLRQGXULQJWKHV\QWKHVLVRI*($DW . DGDSWHG    )LJXUH²7HPSHUDWXUHSURILOHDORQJWLPHIRUFXUUHQWO\XVHG)6,,DQGF\FOLFDFHWDOV IURPJO\FHURODGDSWHG    )LJXUH²6FKHPHRID70%5DDQGD60%5EXQLW  )LJXUH6HWXSXVHGIRUWKHUPRG\QDPLFHTXLOLEULXPH[SHULPHQWV  )LJXUH6FKHPHRIWKHVHWXSXVHGIRUNLQHWLFH[SHULPHQWV  )LJXUH/LQHDUL]DWLRQRIWKHYDOXHVRIHTXLOLEULXPFRQVWDQWVDFFRUGLQJWR9DQ·W+RII HTXDWLRQ  )LJXUH(YROXWLRQRIWKHHTXLOLEULXPFRQVWDQWRIWKHDFHWDOL]DWLRQRIJO\FHUROZLWKWKH OHQJWKRIWKHDOGHK\GHFKDLQ  )LJXUH&DWDO\VWSHUIRUPDQFHVLQWHUPVRIJO\FHUROFRQYHUVLRQDIWHU K DQG K    7 . =   3 EDU = LQLWLDODFHWDOGHK\GHJO\FHUROPRODUUDWLR  ZW RI FDWDO\VW    YL  )LJXUH&DWDO\VWVSHUIRUPDQFHVLQWHUPVRIJO\FHUROFRQYHUVLRQRYHUDQ K SHULRG   7 . =   3 EDU = LQLWLDODFHWDOGHK\GHJO\FHUROPRODUUDWLR  ZW RI FDWDO\VW  )LJXUH²(IIHFWRIWKHVWLUULQJVSHHGLQWKHUHDFWLRQUDWHDVDPHDVXUHPHQWRIH[WHUQDO PDVVWUDQVIHUOLPLWDWLRQV  7 . =   3 EDU = LQLWLDODFHWDOGHK\GHJO\FHURO PRODUUDWLR  ZW RIXQVLHYHG$PEHUO\VWVWLUULQJVSHHGRI USP   )LJXUH(IIHFWRIWKHFDWDO\VWDPRXQWRQWKHUHDFWLRQUDWH  7 . =   3 EDU =  LQLWLDODFHWDOGHK\GHJO\FHUROPRODUUDWLRXQVLHYHG$PEHUO\VWVWLUULQJVSHHGRI  USP   )LJXUH(IIHFWRIWHPSHUDWXUHRQWKHUHDFWLRQUDWH  3 EDU = LQLWLDO DFHWDOGHK\GHJO\FHUROPRODUUDWLRXQVLHYHG$PEHUO\VWVWLUULQJVSHHGRI USP   )LJXUH(IIHFWRIWKHLQLWLDOUHDFWDQWPRODUUDWLRRQWKHUHDFWLRQUDWH  7 . =   3 EDU =   ZW  RIXQVLHYHG$PEHUO\VWVWLUULQJVSHHGRI USP   )LJXUH(IIHFWRQWKHUHDFWLRQUDWHRIWKHSUHVHQFHRISURGXFWVLQWKHLQLWLDOPL[WXUH   3 EDU = LQLWLDODFHWDOGHK\GHJO\FHUROPRODUUDWLR  ZW  RIXQVLHYHG $PEHUO\VWVWLUULQJVSHHGRI USP   )LJXUH(IIHFWRIFDWDO\VWSDUWLFOHVL]HRQWKHUHDFWLRQUDWH  7 . =   3 EDU = LQLWLDODFHWDOGHK\GHJO\FHUROPRODUUDWLR ZW RI$PEHUO\VWVWLUULQJ VSHHGRI USP   )LJXUH(IIHFWRISDUWLFOHVL]HRQFRQYHUVLRQSURILOHLQVLGHWKHFDWDO\VW PLQ DIWHU WKHEHJLQQLQJRIWKHUHDFWLRQ  7 . =   3 EDU = LQLWLDO DFHWDOGHK\GHJO\FHUROPRODUUDWLR  ZW  RIXQVLHYHG$PEHUO\VW  )LJXUH7HUQDU\SKDVHGLDJUDPIRUJO\FHURODFHWRQLWULOHZDWHUDQG JO\FHURODFHWRQLWULOH*($PL[WXUHVLQPRODUFRPSRVLWLRQVDW .   )LJXUH$GVRUSWLRQRQ$PEHUO\VWGHWHUPLQHGE\VZHOOLQJWHVWVSHUIRUPHGDW .  IRU K   )LJXUH&RPSDULVRQRIWKHSHUIRUPDQFHRIWKHVROYHQWVRQWKHNLQHWLFVRIWKH DFHWDOL]DWLRQUHDFWLRQ  7 . =   3 EDU = LQLWLDODFHWDOGHK\GHJO\FHURO PRODUUDWLRVROYHQWPRODUIUDFWLRQRI  ZW RIWKHWRWDOUHDFWDQWVPDVVRI XQVLHYHG$PEHUO\VWVWLUULQJVSHHGRI USP   )LJXUH(IIHFWRIWKHVWLUULQJVSHHGLQWKHUHDFWLRQUDWHDVDPHDVXUHPHQWRIH[WHUQDO PDVVWUDQVIHUOLPLWDWLRQV  7 . =   3 EDU = LQLWLDODFHWDOGHK\GHJO\FHURO PRODUUDWLRVROYHQWPRODUIUDFWLRQRI  ZW RIXQVLHYHG$PEHUO\VW VWLUULQJVSHHGRI USP   )LJXUH(IIHFWRIWHPSHUDWXUHRQWKHUHDFWLRQUDWH  3 EDU = LQLWLDO DFHWDOGHK\GHJO\FHUROPRODUUDWLRVROYHQWPRODUIUDFWLRQRIVWLUULQJVSHHGRI  USP   )LJXUH(IIHFWRIWKHUHDFWDQWVPRODUUDWLRRQWKHUHDFWLRQUDWH  7 . =   3 EDU = VROYHQWPRODUIUDFWLRQRIVWLUULQJVSHHGRI USP     YLL  )LJXUH(IIHFWRIWKHVROYHQWPRODUIUDFWLRQRQWKHUHDFWLRQUDWH  7 . =   3 EDU = LQLWLDODFHWDOGHK\GHJO\FHUROPRODUUDWLRVWLUULQJVSHHGRI USP   )LJXUH²6FKHPHRIWKHVHWXSXVHGIRUWUDFHUDQGEUHDNWKURXJKH[SHULPHQWV  )LJXUH²6FKHPHRIWKHIL[HGEHGFROXPQDDQGWKHPDVVWUDQVIHUPHFKDQLVP EHWZHHQWKHEXONIOXLGDQGWKHFDWDO\VWDGVRUEHQWSDUWLFOHVE  )LJXUH7UDFHUUHVLGHQFHWLPHGLVWULEXWLRQFXUYHV  )LJXUH/DQJPXLUFRPSHWLWLYHDGVRUSWLRQLVRWKHUPIRUWKHELQDU\JO\FHUROD²'062 ERYHU$PEHUO\VWDW  .   )LJXUH/DQJPXLUFRPSHWLWLYHDGVRUSWLRQLVRWKHUPIRUWKHELQDU\:DWHUD²'062 ERYHU$PEHUO\VWDW  .   )LJXUH/DQJPXLUFRPSHWLWLYHDGVRUSWLRQLVRWKHUPIRUWKHELQDU\*($D²'062E RYHU$PEHUO\VWDW  .   )LJXUH([SHULPHQWDODQGSUHGLFWHGEUHDNWKURXJKFXUYHVIRUWKHELQDU\JO\FHURO '062DW  . DQGDIORZUDWHRIDSSUR[LPDWHO\   P/ PLQ − ⋅   )LJXUH([SHULPHQWDODQGSUHGLFWHGEUHDNWKURXJKFXUYHVIRUWKHELQDU\ZDWHU'062 DW  . DQGIORZUDWHVRIDSSUR[LPDWHO\   P/ PLQ − ⋅ DDQG   P/ PLQ − ⋅ E  )LJXUH([SHULPHQWDODQGSUHGLFWHGEUHDNWKURXJKFXUYHVIRUWKHELQDU\*($'062DW  . DQGIORZUDWHVRIDSSUR[LPDWHO\   P/ PLQ − ⋅ DDQG   P/ PLQ − ⋅ E  )LJXUH²6\QWKHVLVRI*($LQDIL[HGEHGDGVRUSWLYHUHDFWRUDW  . E\IHHGLQJD VROXWLRQFRQWDLQLQJ   − ⋅ PRO / RIDFHWDOGHK\GH   − ⋅ PRO / RIJO\FHURODQG   − ⋅ PRO / RI'062DW   − ⋅ P/ PLQ DDQGUHJHQHUDWLRQRIWKHEHGZLWKSXUH '062DW   − ⋅ P/ PLQ E  )LJXUH²,QWHUQDOFRQFHQWUDWLRQSURILOHVRIWKHIL[HGEHGDGVRUSWLYHUHDFWRU  PLQ D  P LQ E  PLQ FDQG  PLQ GDIWHUWKHEHJLQQLQJRIWKHV\QWKHVLVRI*($E\ IHHGLQJDVROXWLRQFRQWDLQLQJ   − ⋅ PRO / RIDFHWDOGHK\GH   − ⋅ PRO / RI JO\FHURODQG   − ⋅ PRO / RI'062DW   − ⋅ P/ PLQ   = 7 .   )LJXUH(IIHFWRIVSDFHWLPHRQWKHPD[LPXPDFKLHYDEOHFRQYHUVLRQIRUWKH V\QWKHVLVRI*($LQDIL[HGEHGDGVRUSWLYHUHDFWRU  = 7 .   =3H  DFHWDOGHK\GHJO\FHURO'062PRODUUDWLRRI  )LJXUH([SHULPHQWDODQGVLPXODWHGEUHDNWKURXJKFXUYHVREWDLQHGE\IHHGLQJ   − ⋅ PRO / RIZDWHU   − ⋅ PRO / RI*($DQG   − ⋅ PRO / RI'062DWD IORZUDWHRI   − ⋅ P/ PLQ WRDIL[HGEHGVDWXUDWHGZLWK   − ⋅ PRO / RIZDWHUDQG   − ⋅ PRO / RI'062DW  .   )LJXUH([SHULPHQWDODQGVLPXODWHGEUHDNWKURXJKFXUYHVREWDLQHGE\IHHGLQJ   − ⋅ PRO / RIZDWHUDQG   − ⋅ PRO / RI'062DWDIORZUDWHRI   − ⋅ P/ PLQ WR DIL[HGEHGVDWXUDWHGZLWK   − ⋅ PRO / RIZDWHU   − ⋅ PRO / RI*($DQG   − ⋅ PRO / RI'062DW  .     YLLL  )LJXUH([SHULPHQWDODQGVLPXODWHGEUHDNWKURXJKFXUYHVREWDLQHGE\IHHGLQJ   − ⋅ PRO / RIZDWHU   − ⋅ PRO / RI*($DQG   − ⋅ PRO / RI'062DWD IORZUDWHRI   − ⋅ P/ PLQ WRDIL[HGEHGVDWXUDWHGZLWK   − ⋅ PRO / RIZDWHUDQG   − ⋅ PRO / RI'062DW  .   )LJXUH([SHULPHQWDODQGVLPXODWHGEUHDNWKURXJKFXUYHVREWDLQHGE\IHHGLQJ   − ⋅ PRO / RIZDWHUDQG   − ⋅ PRO / RI'062DWDIORZUDWHRI   − ⋅ P/ PLQ WR DIL[HGEHGVDWXUDWHGZLWK   − ⋅ PRO / RIZDWHU   − ⋅ PRO / RI*($DQG   − ⋅ PRO / RI'062DW  .   )LJXUH²6FKHPDWLFFRPSDULVRQEHWZHHQ70%5DDQG60%5ERSHUDWLRQPRGH  )LJXUH²/,&26(360%5SLORWXQLW  )LJXUH²([WUDFWDDQGUDIILQDWHEH[SHULPHQWDOFRQFHQWUDWLRQKLVWRU\  )LJXUH²([SHULPHQWDO60%5LQWHUQDOFRQFHQWUDWLRQSURILOHVDWWKHILUVWWKLUGDQG WZHOIWKF\FOHVF\FOLFVWHDG\VWDWHKLJKOLJKWHGZLWKDGRWWHGOLQH  )LJXUH²([SHULPHQWDODQGVLPXODWHG60%5LQWHUQDOFRQFHQWUDWLRQSURILOHVDWWKH F\FOLFVWHDG\VWDWH =  7 .  =   ) $F [ =   ) *O\ [ =   ) '062 [ =   ' '062 [ − = ⋅   ) 4 P/ PLQ  − = ⋅   ' 4 P/ PLQ  − = ⋅   ; 4 P/ PLQ  − = ⋅   5 4 P/ PLQ  − = ⋅   5HF 4 P/ PLQ  = V W PLQ DQGDFRQILJXUDWLRQ  )LJXUH²([SHULPHQWDODQGWKHRUHWLFDO60%5FRQFHQWUDWLRQSURILOHVDWWKHF\FOLFVWHDG\ VWDWHFRQVLGHULQJDGHYLDWLRQRI ± RQWKHUDIILQDWHVWUHDPIORZUDWH   5 4 P/ PLQ − = ⋅ DDQG   5 4 P/ PLQ − = ⋅ E  )LJXUH²([SHULPHQWDODQGWKHRUHWLFDO60%5FRQFHQWUDWLRQSURILOHVDWWKHF\FOLFVWHDG\ VWDWHFRQVLGHULQJDGHYLDWLRQRI ± RQWKHUHF\FOLQJVWUHDPIORZUDWH  )LJXUH²,QILQLWHGLOXWLRQGLIIXVLRQFRHIILFLHQWIRUJO\FHURODFHWDOGHK\GHZDWHUDQG *($LQ'062DW . HVWLPDWHGE\GLIIHUHQWFRUUHODWLRQV  )LJXUH²([SHULPHQWDODQGWKHRUHWLFDO60%5FRQFHQWUDWLRQSURILOHVDWWKHF\FOLFVWHDG\ VWDWHFRQVLGHULQJWKH6LGGLTL/XFDVFRUUHODWLRQIRUWKHHVWLPDWLRQRIWKHGLIIXVLYLWLHV  )LJXUH²([SHULPHQWDODQGWKHRUHWLFDO60%5FRQFHQWUDWLRQSURILOHVDWWKHF\FOLF VWHDG\VWDWHFRQVLGHULQJWKH0DFNLH0HDUHVHTXDWLRQIRUWKHHVWLPDWLRQRIWKH WRUWXRVLW\  )LJXUH²*O\FHURODFHWDOGHK\GHZDWHU*($DQG'062H[WHUQDOPDVVWUDQVIHU FRHIILFLHQWVHVWLPDWHGE\GLIIHUHQWFRUUHODWLRQV  )LJXUH²([SHULPHQWDODQGWKHRUHWLFDO60%5FRQFHQWUDWLRQSURILOHVDWWKHF\FOLF VWHDG\VWDWHFRQVLGHULQJWKH'ZLYHGL8SDGK\D\FRUUHODWLRQIRUWKHHVWLPDWLRQRIWKH H[WHUQDOPDVVWUDQVIHUFRHIILFLHQWV  )LJXUH²([SHULPHQWDODQGWKHRUHWLFDO60%5FRQFHQWUDWLRQSURILOHVDWWKHF\FOLF VWHDG\VWDWHFRQVLGHULQJDFDWDO\VWGHDFWLYDWLRQRI    L[  )LJXUH²%UHDNWKURXJKFXUYHVSHUIRUPHGLQWKHIL[HGEHGDGVRUSWLYHUHDFWRUDQGLQD VLQJOH60%5FROXPQIRUZDWHU'062DDQG*($'062EELQDU\PL[WXUHVDW .  DQGIORZUDWHVRIDSSUR[LPDWHO\  P/ PLQ − ⋅   )LJXUH²([SHULPHQWDODQGWKHRUHWLFDO60%5FRQFHQWUDWLRQSURILOHVDWWKHF\FOLF VWHDG\VWDWHFRQVLGHULQJWKHFRUUHFWHGDGVRUSWLRQSDUDPHWHUVIRUWKHDJHG $PEHUO\VW     [  /LVWRI7DEOHV 7DEOH²5HIHUHQFHIXHOVFKDUDFWHULVWLFV    7DEOH²,QIOXHQFHRIEOHQGLQJJO\FHURODFHWDOVDQGUDSHVHHGPHWK\OHVWHUVZLWKGLHVHO RQSDUWLFOHPDWWHUDQG [ 12 HPLVVLRQV    7DEOH²(IIHFWRQSDUWLFOHVHPLVVLRQVRIWKHDGGLWLRQRI*($WRJDVRLO    7DEOH²/LWHUDWXUHUHYLHZRIFDWDO\VWVXVHGLQDFHWDOL]DWLRQUHDFWLRQV  7DEOH,RQ([FKDQJH5HVLQVWHVWHGLQFDWDO\VWVFUHHQLQJH[SHULPHQWV  7DEOH.LQHWLFH[SHULPHQWVRSHUDWLQJFRQGLWLRQV  7DEOH5HODWLYHPROHFXODUYROXPHDQGVXUIDFHDUHDRISXUHVSHFLHV81,)$& SDUDPHWHUV    7DEOH²%LQDU\LQWHUDFWLRQSDUDPHWHUVIRUWKH81,)$&JURXSVSUHVHQWHGLQ7DEOH    7DEOH²(TXLOLEULXPH[SHULPHQWVFRQGLWLRQVDQGUHVXOWV  3 EDU = DQG   ZW RI $PEHUO\VWZHWXVHGLQDOOH[SHULPHQWV  7DEOH6WDQGDUGHQWKDOS\DQGIUHH*LEEVHQHUJ\RIIRUPDWLRQIRUDOOWKHVSHFLHV  7DEOH(IIHFWRIWKHDOGHK\GHFKDLQOHQJWKRQWKHHTXLOLEULXPFRQYHUVLRQRIWKH DFHWDOL]DWLRQRIJO\FHURODW .   7DEOH(VWLPDWHGNLQHWLFSDUDPHWHUVIRUWKH3+DQG/++:PRGHOVDQGUHVSHFWLYH REMHFWLYHIXQFWLRQYDOXHV  7DEOH.LQHWLFH[SHULPHQWVRSHUDWLQJFRQGLWLRQV  7DEOH²3ULPDU\OLVWRIVROYHQWV  7DEOH5DQNRIVROYHQWVE\SURFHVVSHUIRUPDQFHDQGSURFHVVLPSDFWEDVHGRQWKHLU SURSHUWLHV  7DEOH.LQHWLFSDUDPHWHUVHVWLPDWHGIRUWKHDFHWDOL]DWLRQRIJO\FHUROLQSUHVHQFHRI '062  7DEOH²&RUUHFWHGHVWLPDWLRQRIWKHNLQHWLFSDUDPHWHUVIRUWKHDFHWDOL]DWLRQRI JO\FHUROLQSUHVHQFHRI'062    [L  7DEOH²$PEHUO\VWZHWSK\VLFDOSURSHUWLHV  7DEOH²)L[HGEHGFROXPQSURSHUWLHV  7DEOH²%LQDU\EUHDNWKURXJKH[SHULPHQWDOFRQGLWLRQV  7DEOH²7HUQDU\EUHDNWKURXJKH[SHULPHQWDOFRQGLWLRQV  7DEOH7UDFHUH[SHULPHQWVUHVXOWV  7DEOH²*O\FHUROZDWHU*($DQG'062/DQJPXLUDGVRUSWLRQFRPSHWLWLYHSDUDPHWHUV RYHU$PEHUO\VW  7DEOH²$YHUDJH60%5FROXPQVSURSHUWLHV  7DEOH60%5RSHUDWLQJFRQGLWLRQV  7DEOH0DWKHPDWLFDOPRGHOIRUWKHGHVFULSWLRQRIWKHM WK IL[HGEHGFROXPQRIWKH 60%5ZLWK ∈ ª º ¬ ¼  F Q M  7DEOH60%5SHUIRUPDQFHSDUDPHWHUV  7DEOH%LQDU\EUHDNWKURXJKH[SHULPHQWDOFRQGLWLRQV         &KDSWHU ,QWURGXFWLRQ 7KHVLV)UDPHZRUNDQG3UHVHQWDWLRQ $WWKHSUHVHQWWLPHSHWUROHXPLVVWLOODWWKHFHQWUHRIHQHUJ\DQGWUDQVSRUWDWLRQIXHOV SURGXFWLRQDQGPRVWRIWKHFRXQWULHVZRUOGZLGHDUHGUDVWLFDOO\GHSHQGHQWRQWKLVVRXUFHRI HQHUJ\+RZHYHURYHUWKHODVWGHFDGHVWKHLQFUHDVLQJHQYLURQPHQWDOFRQFHUQVDORQJZLWK WKH DZDUHQHVV RI WKH GHFOLQH RI SHWUROHXP UHVHUYHV DQG LWV FRQVHTXHQW SULFH UDLVLQJ DQG PDUNHWLQVWDELOLW\KDYHEHHQSURPSWLQJWKHGHYHORSPHQWRIDOWHUQDWLYHVWRIRVVLOUHVRXUFHV DQGWKHLPSOHPHQWDWLRQRI´JUHHQHUµSROLFLHV6HYHUDOUHQHZDEOHHQHUJ\VRXUFHVVXFKDVVXQ ZLQG ZDYHV JHRWKHUPDO DQG ELRPDVV KDYH EHHQ LGHQWLILHG DV VXVWDLQDEOH VXEVWLWXWHV IRU SHWUROHXP<HWWKHVWDWHRIWKHDUWRIPRVWRIWKHWHFKQRORJLHVDVVRFLDWHGWRWKHVHUHVRXUFHV LV QRW VXIILFLHQWO\ DGYDQFHG IRU LWV SUHYDOHQFH SULPDULO\ GXH WR LWV UHVWULFWHG HFRQRPLF YLDELOLW\ %LRIXHOV GHULYHG IURP ELRPDVV RQ WKH RWKHU KDQG VHHP WR RYHUFRPH WKH LPSOLFDWLRQV EURXJKWE\WKHH[FHVVLYHXVHRIIRVVLOIXHOVEHLQJDVXVWDLQDEOHHQYLURQPHQWDOO\IULHQGO\DQG FRVWHIIHFWLYHDOWHUQDWLYH,QWKLVW\SHRIIXHOVFDQEHLQFOXGHGHWKDQRODQDOFRKROSURGXFHG IURP FRUQ RU VXJDUFDQH IRU LQVWDQFH ELRGLHVHO PRQRDON\O HVWHUV SURGXFHG WKURXJK WKH UHDFWLRQRIDYHJHWDEOHRLORUDQLPDOIDWZLWKDQDOFRKROVXFKDVPHWKDQRORUHWKDQRODQG ELRJDVPDLQO\REWDLQHGIURPGLJHVWHGRUJDQLFPDWHULDO ,QWKHIXWXUHDWUDQVLWLRQWRZDUGVDELREDVHGHFRQRP\LVH[SHFWHGLQZKLFKELRUHILQHU\ SURFHVVHV ZLOO KDYH D PDMRU UROH +RZHYHU FXUUHQW ELRUHILQHULHV DUH IRFXVHG LQ OLPLWHG IHHGVWRFNDQGSURFHVVLQJWHFKQRORJLHVSURGXFLQJH[FOXVLYHO\DELRIXHO7KHPDMRULW\RIWKH E\SURGXFWVDQGRWKHUFKHPLFDOVSURGXFHGLQWKHVHXQLWVDUHQHJOHFWHGZKLFKFRQVHTXHQWO\ OHDGV WR D GHFUHDVH RI WKH DGGHG YDOXH RI WKH ELRPDVV FKDLQ 5HJDUGLQJ WKH SUHYLRXVO\ PHQWLRQHGGUDZEDFNVD(XURSHDQFROODERUDWLYHSURMHFWZDVFUHDWHGXQGHUWKHGHVLJQDWLRQRI ´(852SHDQ PXOWLOHYHO LQWHJUDWHG %,25()LQHU\ GHVLJQ IRU VXVWDLQDEOH ELRPDVV SURFHVVLQJµ (XUR%LR5HI²SURMHFWZLWKLQZKLFKWKLVZRUNLVGHYHORSHG(XUR%LR5HILQYROYHVHQWLWLHV , 1752'8&7,21     IURP LPSRUWDQW (XURSHDQ LQGXVWULDO JURXSV WR UHVHDUFK ,QVWLWXWHV DQG 8QLYHUVLWLHV IURP  FRXQWULHVZLWKWKHSXUSRVHRIUHSODFLQJWKHH[LVWLQJFRQYHQWLRQDOELRUHILQHULHVE\LQWHJUDWHG ELRUHILQHULHV WKDW ZLOO EH EDVHG RQ WKH SURFHVVLQJ RI VHYHUDO IHHGVWRFN WKURXJK GLIIHUHQW WHFKQRORJLHV LQ RUGHU WR DFKLHYH D GLYHUVLILFDWLRQ RI WKH ILQDO SURGXFWV ,Q WKLV ZD\ WKH SURGXFWLRQ RI ELRIXHOV IURP ELRPDVV DORQJ ZLWK WKH SURGXFWLRQ RI PDUNHWDEOH ELRFKHPLFDO SURGXFWVRIKLJKDGGHGYDOXHZLOOHQKDQFHWKHHIIHFWLYHQHVVRIWKHZKROHELRPDVVFKDLQ 2Q WKH YDQJXDUG RI 5' DQG SURFHVV LQQRYDWLRQ WKH ´/DERUDWRU\ RI 6HSDUDWLRQ DQG 5HDFWLRQ(QJLQHHULQJµ/65(RIWKH´)DFXOGDGHGH(QJHQKDULDGD8QLYHUVLGDGHGR3RUWRµKDG UHFRJQL]HG WKH DIRUHPHQWLRQHG QHHGV RI ELREDVHG LQGXVWU\ DV ZHOO MRLQLQJ (XUR%LR5HI SURMHFW6KDULQJLWVH[SHULHQFHLQLQWHJUDWHGSURFHVVHVHVSHFLDOO\HIILFLHQWHQYLURQPHQWDOO\ IULHQGO\ DQG HFRQRPLFDOO\ DWWUDFWLYH UHDFWLYH VHSDUDWLRQ WHFKQRORJLHV DQG LWV SURIRXQG NQRZOHGJH RI WKH HQHUJ\ LQGXVWU\ /65( LGHQWLI\ JO\FHURO DV D VXLWDEOH IHHGVWRFN IRU WKH V\QWKHVLV RI *O\FHURO(WK\O $FHWDO*($ DSRWHQWLDODGGLWLYHIRUERWKSHWUR DQGELRGLHVHO WKURXJKWKHXVHRID6LPXODWHG0RYLQJ%HG5HDFWRU60%5 *O\FHUROLVDE\SURGXFWRIWKHELRGLHVHOSURGXFWLRQ2QFH(XURSHLVWKHZRUOG·VOHDGLQJ SURGXFHU RI WKLV NLQG RI IXHOV DQG ZLWK WKH H[SHFWHG LQFUHDVH RI LWV PDUNHW JO\FHURO LV EHFRPLQJZLGHO\DYDLODEOHDWORZHUSULFHVWXUQLQJLWLQWRDQLQWHUHVWLQJUDZPDWHULDOIRUWKH V\QWKHVLV RI QHZ DGGHG YDOXH SURGXFWV VLQFH LWV FRQYHQWLRQDO PDUNHW FDQ·W DEVRUE WKLV VXUSOXV $FHWDOV DUH FRPPRQO\ XVHG LQ SHUIXPHV DQG IODYRXULQJ LQGXVWULHV DV ZHOO DV VWDUWLQJ PDWHULDOV IRU DJULFXOWXUDO FKHPLFDOV RU LQWHUPHGLDWHV IRU SKDUPDFHXWLFDOV SURGXFWV 0RUH UHFHQWO\ DWWHQWLRQ KDV EHHQ GUDZQ WR WKH XVH RI WKHVH R[\JHQDWHG RUJDQLF FRPSRXQGV DV DGGLWLYHV IRU IXHOV SUHGRPLQDQWO\ IRU LWV DELOLW\ WR UHGXFH SDUWLFOH HPLVVLRQ DQG LPSURYH HQJLQHVSHUIRUPDQFHV$FHWDOVV\QWKHVLVZKLFKLQYROYHVWKHUPRG\QDPLFHTXLOLEULXPOLPLWHG UHDFWLRQV KDV DOUHDG\ EHHQ VXFFHVVIXOO\ DFKLHYHG RQ FRQWLQXRXV FRXQWHUFXUUHQW FKURPDWRJUDSKLF60%5LQSUHYLRXV/65(WHDPZRUNV7KHDGYDQWDJHRIXVLQJWKLVXQLWLVWKH SRVVLELOLW\WRLQWHJUDWHFKHPLFDOUHDFWLRQDQGFKURPDWRJUDSKLFVHSDUDWLRQRIWKHSURGXFWVLQ D VLQJOH GHYLFH OHDGLQJ WR D FRQYHUVLRQ RI WKH UHDFWDQWV DERYH WKH HTXLOLEULXP OLPLW LQ D KLJKO\HIILFLHQWSURFHVV 7KHUHIRUHQRWRQO\*($V\QWKHVLVLVLQDJUHHPHQWZLWKWKHSULQFLSOHVRIWKHLQWHJUDWHG ELRUHILQHU\WKDWLVLQWHQGHGWREHLPSOHPHQWHGLQDQHDUIXWXUHDVLWVSURGXFWLRQWKURXJKWKH 60%5WHFKQRORJ\LVH[SHFWHGWREHDFRVWHIIHFWLYHDQGHQYLURQPHQWDOIULHQGO\SURFHVV   * /<&(52/$&(7$/6352'8&7,21%< 6 ,08/$7(' 0 29,1* % (' 5 ($&725     %LRGLHVHOFUXGHJO\FHULQHVWLOOKDVWRXQGHUJRVHYHUDOSURFHVVLQJVWHSVLQFOXGLQJVHSDUDWLRQ IURPXQUHDFWHGPHWKDQRODQGS+DGMXVWPHQWVXQWLOLWDFKLHYHVWKHUHTXLUHGSXULW\VWDQGDUGV IRU LWV FRQYHQWLRQDO DSSOLFDWLRQV +RZHYHU WKRVH LQGXVWULHV GHPDQG IRU JO\FHURO KDV EHHQ ODUJHO\VXUSDVVHGGXHWRWKHLQWHQVLILFDWLRQRIELRGLHVHOSURGXFWLRQ 7KHJURZLQJLQWHUHVWRIWKHVFLHQWLILFFRPPXQLW\RQSURFHVVHVXVLQJJO\FHURODVUHQHZDEOH RUJDQLF EXLOGLQJ EORFN LQ RUGHU WR KDQGOH LWV VXUSOXV KDV UHVXOWHG LQ WKH SXEOLFDWLRQ RI QXPHURXVZRUNVVXPPDUL]HGLQVHYHUDOUHYLHZVRYHUWKLVVXEMHFW   $PRQJ WKH JO\FHURO GHULYHG SURGXFWV F\FOLF DFHWDOV DQG NHWDOV VHHP WR KDYH IRXQG D SURPLQHQWSRVLWLRQ&RQYHQWLRQDOO\XVHGLQIRRGDQGFRVPHWLFVLQGXVWULHVDVZHOODVLQVHYHUDO V\QWKHVLV SURFHVVHV WKLV IDPLO\ RI FRPSRXQGV KDYH UHFHQWO\ UHYHDOHG DQ RXWVWDQGLQJ SRWHQWLDODVIXHODGGLWLYHVDOORZLQJQRWRQO\WKHUHGXFWLRQRIIXHOVHPLVVLRQVERWKSDUWLFOH PDWWHUDQGH[KDXVWJDVHV  EXWDOVRLPSURYLQJIXHOVIOXLGSURSHUWLHV  DVFORXGRUIUHH]LQJ SRLQWIRULQVWDQFH7KHLUKLJKVROXELOLW\LQELRPDVVDQGSHWUROHXPGHULYHGGLHVHOVSUHVHQWVDQ DGGLWLRQDODGYDQWDJH 6RONHWDOJO\FHUROIRUPDOJO\FHUROHWK\ODFHWDODQGJO\FHUROEXW\ODFHWDODUHWKHJO\FHURO GHULYHG DFHWDOV WKDW KDYH EHHQ PRUH LQWHQVLYHO\ VWXGLHG LQ WKH RSHQ OLWHUDWXUH 7KHVH FRPSRXQGV DUH JHQHUDOO\ REWDLQHG WKURXJK WKH FRQGHQVDWLRQ RI JO\FHURO ZLWK DFHWRQH   IRUPDOGHK\GH    DFHWDOGHK\GH   DQG EXW\UDOGHK\GH   UHVSHFWLYHO\ 7KH UHDFWLRQ RI JO\FHUROZLWKDOGHK\GHVSURGXFHVWZRDFHWDOVRQHSUHVHQWLQJDILYHPHPEHUHGULQJD GLR[RODQHGHULYDWLYHDQGDQRWKHUSUHVHQWLQJDVL[PHPEHUHGULQJDGLR[DQHGHULYDWLYH GHSHQGLQJRQLIWKHSULPDU\RUVHFRQGDU\K\GUR[\OJURXSIURPJO\FHUROKDVUHDFWHGZLWKWKH DOGHK\GH,WKDVEHHQUHSRUWHGWKDWWKHSURFHVVIRUWKHIRUPDWLRQRIWKHILYHPHPEHUHGLV NLQHWLFDOO\ IDYRXUHG ZKLOH WKH IRUPDWLRQ RI WKH VL[ PHPEHUHG ULQJ LV WKHUPRG\QDPLFDOO\ IDYRXUHG  ,QWKHFDVHRIWKHUHDFWLRQRIJO\FHUROZLWKDFHWRQHRQWKHRWKHUKDQGRQO\WKH ILYHPHPEHUHGULQJLVDOPRVWH[FOXVLYHO\IRUPHG   $FHWDOL]DWLRQVDUHWKHUPRG\QDPLFOLPLWHGUHDFWLRQVWKDWSURGXFHZDWHUDVE\SURGXFW   7KHVHUHDFWLRQVDUHXVXDOO\SHUIRUPHGXQGHUDFLGFDWDO\VLV7KHOLVWRIVXJJHVWHGFDWDO\VWVLV H[WHQVLYH DQG LQFOXGHV GLIIHUHQW W\SHV RI PDWHULDOV ,QRUJDQLF DFLGV     LRQ H[FKDQJH UHVLQV    ]HROLWHV   VLOLFDEDVHG PHVRSRURXV PDWHULDOV   DQG HYHQ LRQLF OLTXLGV   FDWDO\WLFDFWLYLW\KDVEHHQDVVHVVHG+RZHYHUWKH\LHOGVDFKLHYHGZKHQLRQH[FKDQJHUHVLQV DUHXVHGDVFDWDO\VWWRJHWKHUZLWKWKHDGYDQWDJHVDULVLQJIURPKHWHURJHQHRXVFDWDO\VLVFDQ EHFRQVLGHUHGDVDVWURQJLQGLFDWRURIWKHVXSHULRUSHUIRUPDQFHRIWKLVNLQGRIFDWDO\VWVIRU WKLVSDUWLFXODUUHDFWLRQ 7KHUHIRUH WDNLQJ LQ FRQVLGHUDWLRQ DOO WKH SUHYLRXVO\ H[SRVHG LQIRUPDWLRQ RQH FDQ FRQFOXGH WKDW WKH SURGXFWLRQ RI F\FOLF DFHWDOV WKURXJK WKH FRQVXPSWLRQ RI VRPH RI WKH H[FHHGLQJDPRXQWRIJO\FHUROUHDFKLQJWKHPDUNHWIURPWKHELRGLHVHOSURGXFWLRQSURFHVVDQG WKHLU LQFRUSRUDWLRQ LQ WKH ILQDO ELRIXHO IRUPXODWLRQ ZLOO UHSUHVHQW DQ HIIHFWLYH YDORULVDWLRQ VWUDWHJ\ IRU WKLV FRPSRXQG IUDPHG ZLWKLQ WKH VXVWDLQDELOLW\ SULQFLSOHV RI LQWHJUDWHG ELRUHILQHULHV 6 7$7(2)7+( $ 57     )RFXVLQJRQ*($ *O\FHURO (WK\O $FHWDO *($ DOVR WHUPHG HWK\OLGHQH JO\FHURO LV D FRORXUOHVV OLTXLG DW URRP WHPSHUDWXUH   ZLWK D VOLJKW RGRXU WKDW EHFRPHV PRUH LQWHQVH DQG VLPLODU WR DFHWDOGHK\GHV ZKHQ H[SRVHG WR PRLVW DLU GXH WR LWV K\GURO\VLV ,W FRQVLVWV LQ DQ LVRPHULF PL[WXUHRIILYHDQGVL[PHPEHUHGULQJDFHWDOVWKDWFRPSULVHVWKHIROORZLQJFRPSRXQGVFLV K\GUR[\PHWK\OGLR[DQHWUDQVK\GUR[\PHWK\OGLR[DQHFLVK\GUR[\PHWK\O PHWK\OGLR[RODQHDQGWUDQVK\GUR[\PHWK\OPHWK\OGLR[RODQH)LJXUH   D FLV    K\GUR[\PHWK\O    PHWK\O    GLR[RODQH  E FLV    K\GUR[\    PHWK\O    GLR[DQH   F WUDQV    K\GUR[\PHWK\O    PHWK\O    GLR[RODQH  G WUDQV    K\GUR[\    PHWK\O    GLR[DQH  )LJXUH     ²  *($  PHPEHUHGULQJLVRPHUDDQGFDQG  PHPEHUHGULQJLVRPHUEDQG G  *($ V\QWKHVLV ZDV ILUVW UHSRUWHG LQ  LQ D ZRUN SXEOLVKHG E\ +DUQLW]N\ DQG 0HQVFKXWNLQH  WKURXJKWKHFRQGHQVDWLRQRIJO\FHUROZLWKDFHWDOGHK\GHLQDVHDOHGWXEHDW  . $OWKRXJKDOPRVWRQHDQGDKDOIFHQWXU\KDVJRQHVLQFHLWZDVSULPDULO\V\QWKHVL]HG OLWHUDWXUHIRFXVLQJRQWKLVDFHWDOLVUDWKHUVFDUFHZKHQFRPSDUHGZLWKQRQF\FOLFDFHWDOVRU RWKHUJO\FHUROGHULYDWLYHVDVVRONHWDODF\FOLFNHWDOIRUPHGE\WKHUHDFWLRQRIJO\FHUROZLWK DFHWRQHIRULQVWDQFH +RZHYHUDPRQJWKHSRVVLEOHJO\FHUROEDVHGSURGXFWVDFHWDOVKDYH EHHQ UHSRUWHG DV HIIHFWLYH JUHHQ GLHVHO DGGLWLYHV DQG *($ LV RQH RI LWV PRVW SURPLVLQJ GHULYDWLYHV VLQFH LW LV DEOH WR UHGXFH SDUWLFOH HPLVVLRQ DQG HYHQ LPSURYH HQJLQHV SHUIRUPDQFHV  * /<&(52/$&(7$/6352'8&7,21%< 6 ,08/$7(' 0 29,1* % (' 5 ($&725     *($6\QWKHVLV $FHWDOL]DWLRQ5HDFWLRQ 7KH GLUHFW FRQGHQVDWLRQ RI JO\FHURO ZLWK DFHWDOGHK\GH LV DQ DFLG FDWDO\VHG HTXLOLEULXP OLPLWHGUHDFWLRQLQZKLFKZDWHULVIRUPHGDVDE\SURGXFWDFFRUGLQJWRHTXDWLRQ      *O\FHURO  $FHWDOGHK\GH  *($   PHPEHUHG ULQJLVRPHU  *($   PHPEHUHG ULQJLVRPHU :DWHU  $V YHULILHG IRU RWKHU DFHWDOL]DWLRQV WKLV UHDFWLRQ VKRXOG EH H[RWKHUPLF 'HVSLWH WKH DEVHQFH RI UHOLDEOH WKHUPRG\QDPLF GDWD DQ HTXLOLEULXP FRQYHUVLRQ DERYH  DW DSSUR[LPDWHO\  .  LV H[SHFWHG FRQVLGHULQJ WKH UHVXOWV IRU WKH UHDFWLRQ RI JO\FHURO ZLWK RWKHUDOGHK\GHV   7KHDFHWDOL]DWLRQUHDFWLRQLVWKHPRVWFRPPRQSDWKZD\IRUWKHV\QWKHVLVRI*($DQGLW KDVWKHDGYDQWDJHRYHURWKHUPHWKRGVRIGHSHQGLQJRQO\RQIHHGVWRFNWKDWPLJKWEHREWDLQHG IURPELRPDVVJO\FHUROLVDE\SURGXFWIURPWKHELRGLHVHOSURGXFWLRQDQGDFHWDOGHK\GHPD\ EHSURGXFHGE\GHK\GURJHQDWLRQRUSDUWLDOR[LGDWLRQRIELRHWKDQRO  2QWKHRWKHUKDQGLWV PDMRUGUDZEDFNLVUHODWHGZLWKWKHWKHUPRG\QDPLFHTXLOLEULXPOLPLWDWLRQ+RZHYHUVHYHUDO VWUDWHJLHV DUHZLGHO\ HPSOR\HG WR RYHUFRPH WKLVSUREOHP RI DFHWDOL]DWLRQ UHDFWLRQV DV WKH XVHRIDQH[FHVVRIUHDFWDQW  RUWKHXVHRIDUHDFWLYHVHSDUDWLRQPHWKRGIRUWKHFRQWLQXRXV UHPRYDORIZDWHUHLWKHUE\H[WUDFWLRQD]HRWURSLFGLVWLOODWLRQRUDQRWKHUPHWKRG   $QRWKHULVVXHWKDWVKRXOGEHWDNHQLQWRDFFRXQWZKHQGHDOLQJZLWKWKHDFHWDOL]DWLRQRI JO\FHUROZLWKDFHWDOGHK\GH FRQFHUQVWRWKH K\SRWKHWLFDOIRUPDWLRQRIVLGHSURGXFWV GXHWR WKH ROLJRPHUL]DWLRQ RI DFHWDOGHK\GH LQ DFLGLF PHGLD &URWRQDOGHK\GH KH[DGLHQDO DQG SDUDOGHK\GH  ZHUHLGHQWLILHGDVSRVVLEOHVLGHSURGXFWVKRZHYHUDVORQJDVDFHWDOGHK\GH LVQRWSUHVHQWLQODUJHH[FHVVWKHIRUPDWLRQRIWKHVHFRPSRXQGVPLJKWEHQHJOHFWHG 7KH PHFKDQLVP SURSRVHG IRU WKLVUHDFWLRQ   )LJXUH FRPSULVHV WKH IRUPDWLRQ RI DQ KHPLDFHWDOIURPJO\FHUROSULPDU\RUVHFRQGDU\K\GUR[\OJURXSFRQVLGHUHGWKHOLPLWLQJVWHS DQG LWV GHK\GUDWLRQ IRUPLQJ D FDUERFDWLRQ ZKLFK E\ D QXFOHRSKLOLF VXEVWLWXWLRQ PHFKDQLVP 6  1 ZLWK DQ R[\JHQ IURP RQH RI WKH UHPDLQLQJ K\GUR[\O JURXSV RI WKH JO\FHURO PROHFXOH OHDGVWRWKHFORVXUHRIWKHKHWHURDWRPULQJIRUPLQJWKHF\FOLFDFHWDO'HSHQGLQJRQZKLFK K\GUR[\OJURXSSULPDU\RUVHFRQGDU\LVLQYROYHGLQHDFKVWHSWKHSURGXFWRIWKHUHDFWLRQ PLJKWEHWKHVL[PHPEHUHGULQJRUWKHILYHPHPEHUHGULQJLVRPHU  6 7$7(2)7+( $ 57      )LJXUH     ²  6FKHPHIRUWKHUHDFWLRQPHFKDQLVPRIWKHFRQGHQVDWLR QRIJO\FHUROZLWK DFHWDOGHK\GH    $VSUHYLRXVO\PHQWLRQHG+DUQLW]N\DQG0HQVFKXWNLQH  ZHUHWKHILUVWDXWKRUVWRVXJJHVW WKH V\QWKHVLV RI WKHVH DFHWDOV WKURXJK DQ DFHWDOL]DWLRQ UHDFWLRQ E\ KHDWLQJ JO\FHURO DQG DFHWDOGHK\GHWR . LQDVHDOHGWXEH7KHSURGXFWREWDLQHGLQWKHLUZRUNZDVRQO\VOLJKWO\ VROXEOHLQZDWHUDQGERLOHGDWWHPSHUDWXUHVUDQJLQJIURP . WR . SUREDEO\GXHWR WKH SUHVHQFH RI VRPH LPSXULWLHV )ROORZLQJ D VLPLODU SURFHGXUH 1HI  DOVR REWDLQHG *($ KRZHYHU LWV ILQDO SURGXFW ZDV VRPHZKDW GLIIHUHQW IURP WKDW REWDLQHG E\ +DUQLW]N\ DQG 0HQVFKXWNLQH VLQFH LW ZDV VROXEOH LQ ZDWHU $Q DQDORJRXV LQFRQVLVWHQF\ ZDV IRXQG IRU WKH V\QWKHVLV RI EHQ]\OLGHQH JO\FHURO E\ +DUQLW]N\ DQG 0HQVFKXWNLQH DQG RWKHU DXWKRUV   7KLV IDFWZDVPRVWSUREDEO\UHODWHGZLWKWKHDVVD\RIWKHSURGXFWVREWDLQHGE\WKHHDUOLHUDXWKRUV DQG PLJKW EH WKH MXVWLILFDWLRQ IRU WKH GLIIHUHQFHV REVHUYHG LQ WKH ILQDO SURGXFW RI WKH FRQGHQVDWLRQ RI JO\FHURO ZLWK DFHWDOGHK\GH DV ZHOO 'HVSLWH WKDW DVSHFW XQWLO WKDW GDWH QHLWKHU+DUQLW]N\DQG0HQVFKXWNLQHQRU1HIZHUHDEOHWKURXJKWKHLUZRUNVWRVXJJHVWWKH * /<&(52/$&(7$/6352'8&7,21%< 6 ,08/$7(' 0 29,1* % (' 5 ($&725     VL[ PHPEHUHG ULQJ RU WKH ILYH PHPEHUHG ULQJ VWUXFWXUH DV WKH PROHFXODU FRQILJXUDWLRQ RI *($DOWKRXJKERWKUHFRJQL]HGWKHPDVSRVVLEOHWKLVVXEMHFWZDVRQO\FODULILHGLQDZRUNE\ +LOOHWDO  GLVFXVVHGODWHURQ 0DJOLR HW DO   DOVR SXEOLVKHG D VWXG\ IRU WKH V\QWKHVLV DQG TXDQWLILFDWLRQ RI *($ 7KH SURFHGXUHIROORZHGLQFOXGHGWKHXVHRIQDSKWKDERLOLQJSRLQW . DVVROYHQWDQGS WROXHQHVXOIRQLF DFLG 376$ DV FDWDO\VW $FHWDOGHK\GH ZDV SURJUHVVLYHO\ DGGHG WR D IODVN FRQWDLQLQJ JO\FHURO WKH VROYHQW DQG WKH FDWDO\VW DQG WKHQ WKH UHVXOWLQJ KHWHURJHQHRXV PL[WXUHZDVNHSWDWFRQVWDQWWHPSHUDWXUH . XQGHUUHIOX[IRUWKUHHKRXUV$IWHUWKDW SHULRG RI WLPH WKH GHQVHU SKDVH FRQWDLQLQJ *($ ZDV VHSDUDWHG IURP WKH VROYHQW QHXWUDOL]HGGULHGDQGILOWHUHG*($ZDVWKHQVHSDUDWHGIURPDFHWDOGHK\GHDQGJO\FHUROE\ WZR FRQVHFXWLYH GLVWLOODWLRQV DWPRVSKHULF DQG YDFXXP GLVWLOODWLRQ IRU HDFK UHDFWDQW UHVSHFWLYHO\REWDLQLQJDFRORXUOHVVOLTXLG7KLVSURFHVVDFKLHYHGD\LHOG ,Q6KHYFKXNHWDO  SURFHHGHGWRDGHHSHUVWXG\RIWKHDFHWDOL]DWLRQRIJO\FHURO ZLWKORZHUDOGHK\GHVDFHWDOGHK\GHSURSLRQDOGHK\GHDQGEXW\UDOGHK\GH7KHUHDFWLRQVZHUH SHUIRUPHG XQGHU YLJRURXV VWLUULQJ IRU D SHULRG RI RQH KRXU LQ D WHPSHUDWXUH FRQWUROOHG UHDFWRUDWWDFKHGWRDUHIOX[FRQGHQVHU7KHPRODUUDWLREHWZHHQJO\FHURODQGWKHDOGHK\GH ZDVDQG376$ZDVXVHGDVFDWDO\VWUHSUHVHQWLQJRIWKHPRODUDPRXQWRIJO\FHURO7KH UHDFWLRQSURGXFWZDVVXEVHTXHQWO\VXEMHFWHGWRWZRUHGXFHGSUHVVXUHGLVWLOODWLRQVLQRUGHUWR UHPRYH WKH UHPDLQLQJ UHDFWDQWV ILQDOO\ DWWDLQLQJ D FRORXUOHVV OLTXLG 7KLV OLTXLG ZDV FRPSRVHGE\DQLVRPHULFPL[WXUHRIF\FOLFDFHWDOVWKHFLVDQGWUDQVIRUPVRIWKHVL[DQG ILYHPHPEHUHGULQJVZLWKDERLOLQJSRLQWRI .  . DWPP+JZKHQDFHWDOGHK\GH ZDVXVHGDVVWDUWLQJPDWHULDOZLWKD\LHOGRIDSSUR[LPDWHO\7KLVSURFHGXUHDOORZHGWKH GHWHUPLQDWLRQ RI NLQHWLF DQG HTXLOLEULXP SDUDPHWHUV IRU WKHVH DFHWDOL]DWLRQ UHDFWLRQV +RZHYHU UHVXOWV UHSRUWHG E\ 6KHYFKXN VHHP WR EH LQFRQVLVWHQW VLQFH LW LV QRW SRVVLEOH WR REVHUYHDWUHQGEHWZHHQWKHHTXLOLEULXPFRQVWDQWRUUHDFWLRQUDWHZLWKWKHLQFUHDVHRIWKH OHQJWKRIWKHDOGHK\GHFKDLQLQRSSRVLWLRQWRZKDWZDVSRVVLEOHWRFRQFOXGHIURPDVWXG\ SHUIRUPHGE\ Silva HWDO  ZKHUHWKHLQFUHDVHRIWKHVL]HRIWKHDOGHK\GHFKDLQIURP  & WR  & OHDGWRDVLJQLILFDQWGHFUHDVHLQWKHDFHWDOL]DWLRQHTXLOLEULXPFRQYHUVLRQDQGNLQHWLFV ZLWKDPD[LPXPFRQYHUVLRQDIWHUKRXUVRIWRUHVSHFWLYHO\ ,QRUGHU WR LPSURYH WKH \LHOG RI WKLV SURFHVV 6KHYFKXN SURSRVHGD VOLJKW FKDQJH LQ LWV SURFHGXUH2QFHDFHWDOL]DWLRQVDUHHTXLOLEULXPOLPLWHGUHDFWLRQVWKHXVHRIH[FHVVRIRQHRI WKHUHDFWDQWVSUHIHUDEO\WKHDOGHK\GHGXHWRLWVORZHUHQHUJ\UHTXLUHPHQWVIRUUHFRYHU\RU LWVJUDGXDOIHHGLQJWRWKHV\VWHPZHUHVXJJHVWHGDVFRQYHUVLRQHQKDQFLQJVWUDWHJLHV $ILQDOFRQFOXVLRQWKDWFDQEHZLWKGUDZQIURP6KHYFKXNVWXG\UHJDUGVWRWKHLQIOXHQFHRI WKHXVHRIVROYHQWVLQDFHWDOL]DWLRQRIJO\FHUROZLWKORZHUDOGHK\GHV&RQWUDU\WRZKDWZDV REVHUYHG IRU WKH V\QWKHVLV RI F\FOLF NHWDOV ZKHUH WKH XVH RI DQ DSSURSULDWH VROYHQW DFHWRQLWULOH DQG GLR[RODQH IRU LQVWDQFH FRXOG LQFUHDVH WKH SURFHVV \LHOG WKH FRQGHQVDWLRQ RI JO\FHURO ZLWK DOGHK\GHV ZDV QHJDWLYHO\ DIIHFWHG E\ WKH XVH RI GLIIHUHQW 6 7$7(2)7+( $ 57     RUJDQLFVROYHQWVLQFOXGLQJWHWUDK\GURIXUDQGLPHWK\OIRUPDPLGHDFHWRQLWULOHF\FORKH[DQH GLR[DQHDQGKH[DQH )ROORZLQJDSURFHGXUHVLPLODUWRZKDWZDVSUHYLRXVO\UHSRUWHGE\0DLOODUGHWDO  LQ )HUUHLUD HW DO   SHUIRUPHG WKH V\QWKHVLV RI *($ IURP DFHWDOGHK\GH DQG JO\FHURO XVLQJ WROXHQHDVVROYHQWDQG376$DVFDWDO\VWZLWKVRGLXPVXOSKDWHXQGHUUHIOX[FRQGLWLRQVRYHU DWHQKRXUSHULRG7KHSURGXFWRIWKHUHDFWLRQZDVWKHQSXULILHGE\GLVWLOODWLRQDQGH[WUDFWLRQ ZLWKHWKHUZKLFKZDVSRVWHULRUO\UHPRYHGE\HYDSRUDWLRQ7KHDQDO\VLVRIWKHHYROXWLRQRI HDFKLVRPHUE\WKHVHDXWKRUVFRUURERUDWHGWKHPHFKDQLVPSUHVHQWHGRQ)LJXUHDVLWZLOO EHGLVFXVVHGDIWHUZDUGVLQ6HFWLRQ $ZDUHRIWKHDGYDQWDJHVRIWKHXVHRIKHWHURJHQHRXVFDWDO\VWVDQGUHDFWLYH VHSDUDWLRQ XQLWV 0LOOHU HW DO   SDWHQWHG D FRQWLQXRXV SURFHVV IRU WKH V\QWKHVLV RI *($ EOHQGHG LQ ELRGLHVHO 7KH SURFHVV FRPSULVHV WZR SULPDU\ UHDFWRUV RQH WR ZKLFK DQ DOFRKRO DQG D WULJO\FHULGH DUH IHG DQG SDUWLDOO\ FRQYHUWHG WR ELRGLHVHO DQG JO\FHURO DV D E\SURGXFW E\ WUDQVHVWHULILFDWLRQWRIDWW\DFLGHVWHUV)$(DQGDQRWKHULQZKLFKDQDOGHK\GHLVSURGXFHGE\ FDWDO\WLF R[LGDWLRQ RI DQ DOFRKRO 7KH RXWOHW VWUHDPV RI WKHVH UHDFWRUV DUH WKHQ IHG WR D UHDFWLYH GLVWLOODWLRQ FROXPQ ZKHUH WKH DOFRKRO DQG WKH WULJO\FHULGH VXIIHU IXUWKHU WUDQVHVWHULILFDWLRQ DQG JO\FHURO UHDFWV ZLWK WKH SUHYLRXVO\ V\QWKHVL]HG DOGHK\GH WR IRUP D JO\FHURODFHWDO)LJXUH   )LJXUH     ²  )ORZVKHHWIRUWKH  FRQWLQXRXV SURGXFWLRQRIELRGLHVHOFRQWDLQLQJDJO\FHURO DFHWDODGGLWLYHREWDLQHGE\DQDFHWDOL]DWLRQUHDFWLRQDGDSWHG    (WKDQROLVUHFRPPHQGHGDVWKHDOFRKROWREHXVHGLQWUDQVHVWHULILFDWLRQUHDFWLRQIRUWKLV SURFHVVLQVWHDGRIPHWKDQRORURWKHUORZHUDOFRKROVIURP & WR & LQFRQWUDVWWRFRPPRQ EDWFK)$(SURGXFWLRQPHWKRGVZKHUHLQH[SHQVLYHPHWKDQROEHFRPHVDGYDQWDJHRXVRQFHLW GRHV QRW GLVVROYH QHLWKHU LQ ELRGLHVHO QRU JO\FHURO RIIHULQJ DQ HFRQRPLFDO PHDQ RI VHSDUDWLRQ+RZHYHUDVDFRQWLQXRXVSURFHVVZDVLQWHQGHGWREHLPSOHPHQWHGLQWKLVZRUN * /<&(52/$&(7$/6352'8&7,21%< 6 ,08/$7(' 0 29,1* % (' 5 ($&725     DQGDVLQJOHSKDVHV\VWHPZDVUHTXLUHGVRWKDWWKHDGGLWLRQRIPDVVWUDQVIHUUHVLVWDQFHVFRXOG EHDYRLGHGHWKDQRODEHWWHUVROYHQWIRUELRGLHVHODQGJO\FHUROWKDQPHWKDQROZDVVHOHFWHG DVDOFRKROIHHGVWRFN)XUWKHUPRUHDFHWDOGHK\GHLVWKHUHFRPPHQGHGDOGHK\GHRQFHLWFDQ UHDGLO\EHSURGXFHGE\FDWDO\WLFR[LGDWLRQRIHWKDQRO 6HYHUDOVWUDWHJLHVZHUHDGRSWHGE\WKHDXWKRUVWRHQKDQFHWKLVSURFHVV\LHOG7KHILUVW UHJDUGVWRWKHXVHRILRQH[FKDQJHUHVLQV+HWHURJHQHRXVFDWDO\VLVDYRLGVVHYHUDOSUREOHPVRI WKH XVH RI VROXEOH LQRUJDQLF DFLGV DV 376$ FDWDO\VW SURSRVHG E\ WKH PDMRULW\ RI SULRU DXWKRUVVXFKDVLWVQHXWUDOL]DWLRQDIWHUWKHUHDFWLRQDQGWKHVHSDUDWLRQDQGSXULILFDWLRQRI WKHGHVLUHGSURGXFW$OXPLQRVLOLFDWHVVROLGFDWDO\VWVVXFKDV]HROLWHV<%($DQG=60IRU LQVWDQFHUHYHDOHGWREHJRRGFDWDO\VWVIRUDFHWDOL]DWLRQVKRZHYHUDFLGLRQH[FKDQJHUHVLQV KDYHEHHQGHPRQVWUDWHGDVSDUWLFXODUO\HIIHFWLYHIRUWKLVW\SHRIUHDFWLRQ   7KHVHFRQG \LHOGHQKDQFLQJVWUDWHJ\LVUHODWHGWRWKHXVHRIDUHDFWLYHVHSDUDWLRQXQLW7KHRXWOHWVWUHDP RI WKHWUDQVHVWHULILFDWLRQUHDFWRUFRPSRVHGE\D PL[WXUHRIELRGLHVHOJO\FHUROXQUHDFWHG YHJHWDEOHRLODQGDOFRKRORQFHWKLVLVDQHTXLOLEULXPOLPLWHGUHDFWLRQLVIHGDWWKHWRSRID FRQWLQXRXVFRXQWHUFXUUHQWIORZUHDFWLYHGLVWLOODWLRQFROXPQZKLOHWKHDFHWDOGHK\GHVWUHDP VWLOO FRQWDLQLQJ VRPH HWKDQRO LV IHG DW WKH ERWWRP RI WKLV FROXPQ 7KXV WKH KHDYLHU FRPSRXQGV )$( WULJO\FHULGH DQG JO\FHURO PRYH GRZQZDUGV LQ WKH FROXPQ ZKHUHDV WKH OLJKWHUFRPSRXQGVHWKDQRODFHWDOGHK\GHDQGZDWHUPRYHXSZDUGVSURPRWLQJWKHFRQWDFW RI DOO WKRVH VSHFLHV DW WKH FROXPQ UHDFWLYH ]RQH ZKLFK H[WHQGV WKH FRQYHUVLRQ RI WULJO\FHULGHVZLWKHWKDQRODQGDOORZVWKHIRUPDWLRQRIWKHJO\FHURODFHWDOILQDOO\DFKLHYLQJD VWUHDP FRQWDLQLQJ WKH ELRGLHVHO ZLWK *($ DW WKH ERWWRP RI WKH FROXPQ DQG D VWUHDP FRQWDLQLQJHWKDQRODFHWDOGHK\GHDQGZDWHUDWLWVWRSWKDWFDQEHGLVWLOOHGLQDQDGGLWLRQDO XQLWLQRUGHUWRUHF\FOHWKHDOFRKRODQGWKHDOGHK\GHDQGUHPRYHZDWHUIURPWKHV\VWHP 7KH DVVHVVPHQW RI WKLV SURFHVV ZDV FRQGXFWHG RQO\ E\ FRPSXWDWLRQDO VLPXODWLRQ XVLQJ $VSHQ3OXV  VRIWZDUH+RZHYHULWVEHQHILWVDUHFOHDUVLQFHQRWRQO\LWVXJJHVWVDFRQWLQXRXV SURFHVVIRUWKHSURGXFWLRQRIELRGLHVHOFRQWDLQLQJDJO\FHURODFHWDODGGLWLYHWKDWFDQLPSURYH WKHIXHOSHUIRUPDQFHE\UHGXFLQJLWVSDUWLFXODWHHPLVVLRQXSWR  DVLWUHSUHVHQWVDFRVW HIIHFWLYHDQGHQYLURQPHQWDOIULHQGO\SDWKZD\IRUELRGLHVHOSURGXFWLRQLQFUHDVLQJWKHSURFHVV \LHOGE\DSSUR[LPDWHO\WKURXJKWKHLQFRUSRUDWLRQRIJO\FHUROLQJO\FHURODFHWDOIRUPLQ WKHILQDOSURGXFWDQGHOLPLQDWLQJWKHKLJKFRVWVDQGHQHUJ\UHTXLUHPHQWVRIWKHVHSDUDWLRQRI WKLVSRO\DOFRKRO 7KH PDMRU GUDZEDFN RI WKLV SURFHVV LV UHODWHG WR WKH IRUPDWLRQ RI ZDWHU GXULQJ WKH V\QWKHVLVRIWKHJO\FHURODFHWDOZKLFKFDQOHDGWRWKHK\GURO\VLVRIWKH)$(DQGSURPRWHWKH GLPLQLVKLQJRIWKHFDWDO\WLFDFWLYLW\RIWKHLRQH[FKDQJHUHVLQ$OWKRXJKWKHXVHRIDUHDFWLYH GLVWLOODWLRQ SURFHVV DWWHPSWV WR PLQLPL]H WKLV IDFW E\ WKH FRQWLQXRXV ZDWHU UHPRYDO WKLV SUREOHPFDQEHFRPSOHWHO\HOLPLQDWHGE\SURFHHGLQJWRDWUDQVDFHWDOL]DWLRQUHDFWLRQLQVWHDG RIWKHGLUHFWFRQGHQVDWLRQRIJO\FHUROZLWKDFHWDOGHK\GHDVLWZLOOEHGLVFXVVHGLQIXUWKHU GHWDLOLQ6HFWLRQ 6 7$7(2)7+( $ 57     ,Q RQH RI WKH ODWHVW ZRUNV UHJDUGLQJ WKH V\QWKHVLV RI *($ $JLUUH HW DO   VWXGLHG WKH NLQHWLFEHKDYLRXURIWKHDFHWDOL]DWLRQUHDFWLRQ7KHH[SHULPHQWVZHUHSHUIRUPHGLQDEDWFK UHDFWRU ZLWK D UHIOX[ FRQGHQVHU ZKHUH WKH UHDFWDQWV ZHUH SXW LQ FRQWDFW ,Q RUGHU WR GHFUHDVHWKHYLVFRVLW\RIWKHLQLWLDOJO\FHURODFHWDOGHK\GHPL[WXUHRIZDWHUZDVDGGHG WRWKHLQWHQGHGJO\FHURODPRXQW7KHDXWKRUVDOVRVWDWHWKDWJO\FHUROZLWKDQDVVD\DERYH LV GLIILFXOW WR REWDLQ IURP WKH LQGXVWULDO ELRGLHVHO SURFHVV ZKLFK ZRXOG MXVWLI\ WKH LQWURGXFWLRQ RI ZDWHU DV ZHOO $OWKRXJK ZDWHU LV RQH RI WKH SURGXFWV RI WKH UHDFWLRQ LWV DGGLWLRQWRWKHV\VWHPGLGQRWGHFUHDVHVLJQLILFDQWO\WKHHTXLOLEULXPFRQYHUVLRQZKLFKZDV DOZD\V FORVH WR  7KH UHDFWLRQ ZDV LQ IDFW FRQVLGHUHG LUUHYHUVLEOH IRU WKH UDQJH RI FRQGLWLRQVVWXGLHG 7KH DFHWDOL]DWLRQ UHDFWLRQ PHFKDQLVP LV DOVR GLVFXVVHG LQ WKH SDSHU $OWKRXJK QR H[SHULPHQWDO HYLGHQFHV DUH SUHVHQWHG E\ WKH DXWKRUV D PHFKDQLVP FRQVLGHULQJ WKH IRUPDWLRQRIWKHKHPLDFHWDOLQWHUPHGLDWHVLPLODUWRWKHSUHVHQWHGLQ)LJXUHLVDVVXPHG $Q LQWHUHVWLQJ UHPDUN UHJDUGLQJ WKLV UHDFWLRQ LV WKH IDFW WKDW WKH DFHWDO IRUPDWLRQ RFFXUV HYHQLQWKHDEVHQFHRIWKHFDWDO\VWHYLGHQFHGE\WKHWHPSHUDWXUHLQFUHDVHZKHQWKHWZR UHDFWDQWVDUHPL[HGEXWWKHUHDFWLRQUDWHLVWRRORZ $VLPSOHILUVWRUGHUUHDFWLRQUDWHPRGHOWRZDUGVDFHWDOGHK\GHZDVFRQVLGHUHGWRGHVFULEH WKH H[SHULPHQWDO NLQHWLF UHVXOWV LQ WKH SUHVHQFH RI $PEHUO\VW 7KH DEVHQFH RI H[WHUQDO PDVVWUDQVIHUUHVLVWDQFHVZDVGHPRQVWUDWHGZKLOHLQWUDSDUWLFOHUHVLVWDQFHVZHUHQHJOHFWHG )RUWHPSHUDWXUHVUDQJLQJIURP . WR . DQGDJO\FHUROWRDFHWDOGHK\GHPRODUUDWLRRI DUHDFWLRQDFWLYDWLRQHQHUJ\RI − ⋅  NPRO ZDVREVHUYHG7KLVYDOXHLVLQDJUHHPHQW ZLWKWKDWSXEOLVKHGE\WKHVDPHDXWKRUVIRUWKHFRQGHQVDWLRQRIJO\FHUROZLWKIRUPDOGHK\GH  − ⋅  NPRO  DQGZLWKWKHSXEOLVKHGE\1DQGDHWDOIRUWKHFRQGHQVDWLRQRIJO\FHUROZLWK DFHWRQH  − ⋅  NPRO   $ ILQDO UHPDUN VKRXOG EH OHIW WR WKH IRUPDWLRQ RI WULR[DQH DV D VHFRQGDU\ SURGXFW ZKHQ DFHWDOGHK\GH LV SUHVHQW LQ H[FHVV IRUPHG DIWHU JO\FHURO EHLQJ FRPSOHWHO\FRQVXPHG  7UDQVDFHWDOL]DWLRQ5HDFWLRQ ,QWKHSUHVHQFHRIDQDFLGFDWDO\VWJO\FHUROUHDFWVZLWKDQDFHWDOH[RWKHUPLFDOO\WRIRUP *($LVRPHULFPL[WXUHSUHVHQWHGLQ)LJXUHDQGWKHFRUUHVSRQGLQJDOFRKROVDFFRUGLQJWR HTXDWLRQ     $FHWDO *O\FHURO  *($  PHPEHUHG ULQJLVRPHU *($  PHPEHUHG ULQJLVRPHU $OFRKROV   * /<&(52/$&(7$/6352'8&7,21%< 6 ,08/$7(' 0 29,1* % (' 5 ($&725     ,QDSDWHQW'HOIRUWHWDO  GHVFULEHGWKHV\QWKHVLVRI*($YLDWUDQVDFHWDOL]DWLRQRI GLHWKR[\HWKDQH '(( ZLWK JO\FHURO LQ D EDWFK UHDFWRU DW URRP WHPSHUDWXUH IRU IRXU KRXUV7KHDFLGLRQH[FKDQJHUHVLQ$PEHUO\VWZDVXVHGDVFDWDO\VWDQG'((ZDVSUHVHQWLQ H[FHVV LQLWLDO UHDFWDQWV PRODU UDWLR '((JO\FHURO ODUJHU WKDQ  $IWHU ILOWHULQJ WKH ILQDO UHDFWLRQ PL[WXUH WR UHPRYH WKHFDWDO\VW *($ ZDV LVRODWHG E\ GLVWLOODWLRQRI WKH UHPDLQLQJ UHDFWDQWVDQGE\SURGXFWVXQGHUUHGXFHGSUHVVXUHREWDLQLQJDFRORXUOHVVOLTXLGVROXEOHLQJDV RLOFRPSULVLQJWKHIRXULVRPHUVRIWKLVDFHWDO $V GLVFXVVHG LQ 6HFWLRQ   0LOOHU HW DO SDWHQWHG ZRUN   IRU WKH SURGXFWLRQ RI ELRGLHVHO FRQWDLQLQJ JO\FHURO DFHWDOV DV DGGLWLYHV PHQWLRQHG WKH QHJDWLYH LPSDFW RI WKH SUHVHQFH RI ZDWHU IRUPHG DV D SURGXFW RI WKH GLUHFW FRQGHQVDWLRQ RI JO\FHURO ZLWK DOGHK\GHVLQWKHFDWDO\WLFDFWLYLW\RIWKHSURSRVHGLRQH[FKDQJHUHVLQVDQGLQWKHTXDOLW\RI WKH ILQDO IXHO +HQFH WUDQVDFHWDOL]DWLRQ UHDFWLRQ ZDV SURSRVHG DV SUHIHUDEOH URXWH IRU REWDLQLQJWKHJO\FHURODFHWDODGGLWLYHVLQFHLQVWHDGRIZDWHUWKHE\SURGXFWRIWKLVUHDFWLRQ LV DQ DOFRKRO WKDW FDQ EH LQWHJUDWHG LQ WKH ELRGLHVHO FRPSRVLWLRQ 7KHUHIRUH WKLV SURFHVV ZRXOGFRPSULVHWZRUHDFWRUVLQDQLQLWLDOVWDJHUHDFWRULVUHVSRQVLEOHIRUWKHFRQYHUVLRQRI HWKDQRODQGWULJO\FHULGHLQWRIDWW\DFLGHWK\OHVWHU)$((DQGJO\FHURODQGUHDFWRUIRUWKH FRQYHUVLRQRIHWKDQRODQGDFHWDOGHK\GHLQWR'((DQGZDWHU$SUHVVXUHVZLQJDGVRUSWLRQXQLW ZLOOHQVXUHWKHUHPRYDORIZDWHUIURPWKHRXWOHWVWUHDPRIUHDFWRU7KLVVWUHDPZLOOWKHQ EHIHGWRWKHERWWRPRIDFRQWLQXRXVFRXQWHUFXUUHQWIORZUHDFWLYHGLVWLOODWLRQFROXPQZKLOH WKHRXWOHWVWUHDPRIUHDFWRULVLQWURGXFHGRQWKHWRSRIWKLVFROXPQ&RQVHTXHQWO\OLJKWHU FRPSRXQGVDVHWKDQRODQG'((ZLOOPRYHXSZDUGVLQWKHFROXPQZKLOHKHDYLHUFRPSRXQGV DV )$( WULJO\FHULGH DQG JO\FHURO ZLOO WUDYHO LQ WKH RSSRVLWH GLUHFWLRQ )URP WKHVH UHYHUVH PRYHPHQWVDQGWKHFRQWDFWRIDOOWKHVSHFLHVLQWKHFHQWUDOSDUWRIWKHUHDFWLYHGLVWLOODWLRQ FROXPQUHDFWLYH]RQHWKHWUDQVHVWHULILFDWLRQOLPLWHGUHDFWLRQZLOOEHGLVSODFHGLQIDYRXURI WKHSURGXFWVDQG*($V\QWKHVLVE\WUDQVDFHWDOL]DWLRQRI'((ZLWKJO\FHUROZLOOEHDFKLHYHG 7ZRILQDOVWUHDPVZLOOEHREWDLQHGIURPWKLVXQLWWKHWRSVWUHDPZLOOEHFRPSRVHGRIPDLQO\ XQUHDFWHG HWKDQRO DQG '(( WKH ERWWRP VWUHDP ZLOO EH FRQVWLWXWHG E\ D PL[WXUH RI WKH ELRGLHVHODQGWKH*($DGGLWLYH)LJXUH  6 7$7(2)7+( $ 57     )LJXUH     ²  )ORZVKHHWIRUWKHFRQWLQXRXVSURGXFWLRQRIELRGLHVHOFRQWDLQ LQJDJO\FHURO DFHWDODGGLWLYHREWDLQHGE\WUDQVDFHWDOL]DWLRQUHDFWLRQDGDSWHG    $GHHSVWXG\RIWKHWUDQVDFHWDOL]DWLRQUHDFWLRQZDVXQGHUWDNHQE\;L+RQJHWDO  ,QDQ LQLWLDO VWDJH WKH H[LVWHQFH RI VHFRQGDU\ UHDFWLRQV ZDV DVVHVVHG EHLQJ SRVVLEOH WR LGHQWLI\ VHYHUDOE\SURGXFWVLQFOXGLQJDQKHPLDFHWDOIURPJO\FHUROHWK\OYLQ\OHWKHUDQGVRPHRILWV ROLJRPHUV DQG D FRPSOH[ FRPSRXQG FRQWDLQLQJ WZR DFHWDO VWUXFWXUHV UHVXOWLQJ IURP WKH DOFRKRO H[FKDQJH RI WKH IUHH K\GUR[\O JURXS RI *($ ZLWK '(( $OWKRXJK QR UHDFWLRQ PHFKDQLVPZDVVXJJHVWHGE\WKHDXWKRUVWKHGHWHFWLRQRIWKHKHPLDFHWDOOHDGVWREHOLHYH WKDWWKLVLVDVWHSZLVHUHDFWLRQZKHUHWKHKHPLDFHWDODFWVDVDQLQWHUPHGLDWHRIWKHILQDO SURGXFW *LYHQ WKDW D WZR SKDVH PL[WXUH LV REWDLQHG ZKHQ JO\FHURO LV PL[HG ZLWK '(( WKH HYDOXDWLRQ RI WKH XVH RI D VROYHQW WR RYHUFRPH WKLV SUREOHP ZDV SHUIRUPHG (WKDQRO ZDV LGHQWLILHGDVDVXLWDEOHVROYHQWIRUWKLVUHDFWLRQ7KHDGGLWLRQRISDUWVRIHWKDQROWRD JO\FHURO'((PL[WXUHKDVSURYHQWREHDEOHWRHOLPLQDWHWKHPLVFLELOLW\SUREOHPVEHWZHHQWKH UHDFWDQWVZKLOHSDUWVZKHUHUHTXLUHGIRUDPL[WXUH6LQFHHWKDQROLVDSURGXFWIURP WKHWUDQVDFHWDOL]DWLRQLWVXVHDVVROYHQWZDVH[SHFWHGWRSURPRWHDVLJQLILFDQWGHFUHDVHRQ WKH HTXLOLEULXP FRQYHUVLRQ +RZHYHU GXH WR WKH KLJK YDOXH RI WKH HTXLOLEULXP FRQVWDQW UHSRUWHGIRUWKLVUHDFWLRQRQO\DVOLJKWGHFOLQHRIWKHHTXLOLEULXPFRQYHUVLRQZDVREVHUYHG IURPWRZKHQFRPSDUHGWRWKHVROYHQWIUHHV\QWKHVLVDVVXPLQJLQHLWKHUFDVHD JO\FHURO'((UDWLR )URP WKH FRQFHQWUDWLRQEDVHG HTXLOLEULXP FRQVWDQW VWXG\ IRU WKH *($ IRUPDWLRQ DQ HQWKDOS\ RI  − ⋅  NPRO  ZDV HVWLPDWHG 7KH PRVW VLJQLILFDQW FRQFOXVLRQ WKDW FDQ EH ZLWKGUDZQIURPWKHVHUHVXOWVLVWKHH[RWKHUPLFEHKDYLRXURIWKHWUDQVDFHWDOL]DWLRQDVLWLV REVHUYHG IRU DFHWDOL]DWLRQ UHDFWLRQV DVZHOODQGLWV KLJKYDOXHRIHTXLOLEULXP FRQVWDQWDV SUHYLRXVO\PHQWLRQHG ,Q WKH VDPH SDSHU WKH DXWKRUV VWXG\ WKH NLQHWLF EHKDYLRXU RI WKH UHDFWLRQ LQ WKH SUHVHQFHRI$PEHUO\VW7KHH[LVWHQFHRIPLOGLQWUDSDUWLFOHPDVVWUDQVIHUUHVLVWDQFHVZDV * /<&(52/$&(7$/6352'8&7,21%< 6 ,08/$7(' 0 29,1* % (' 5 ($&725      7DEOH²5HIHUHQFHIXHOVFKDUDFWHULVWLFV   3URSHUWLHV 5HIHUHQFH)XHO 5HIHUHQFH)XHO 'HQVLW\NJͼP     &HWDQH1XPEHU   6XOSKXU&RQWHQWSSP   2[\JHQ   &DUERQ   ,QLWLDO%RLOLQJ3RLQW.   )LQDO%RLOLQJ3RLQW.   $URPDWLFV     :KHQXVHGZLWKRXWDQ\DGGLWLYHUHIHUHQFHIXHOVDQGSUHVHQWHGSDUWLFOHVHPLVVLRQVRI DSSUR[LPDWHO\  − ⋅  J NP   DQG  − ⋅  J NP  ZKLOH WKH SROOXWDQWV HPLVVLRQV QDPHO\  [ 12 ZHUHDSSUR[LPDWHO\ − ⋅  J NP DQG − ⋅  J NP UHVSHFWLYHO\ 5HVXOWVUHODWLYHWREOHQGVZLWKUHIHUHQFHIXHOVKRZQWKDW*($YROLQUHIHUHQFHIXHO ZDVDEOHWRUHGXFHSDUWLFOHPDWWHUHPLVVLRQLQDSSUR[LPDWHO\KDYLQJRQO\DVOLJKWO\ QHJDWLYH LPSDFW RQ WKH [ 12  *%$  YRO LQ UHIHUHQFH IXHO  WKH RWKHU DFHWDO XQGHU HYDOXDWLRQKDGDVLPLODUEHKDYLRXULQZKDWFRQFHUQVSDUWLFOHVHPLVVLRQVSURPRWLQJDQHYHQ ORZHU LQFUHDVH LQ WKH [ 12  %RWK FRPSRXQGV SUHVHQWHG VLJQLILFDQW EHWWHU UHVXOWV ZKHQ FRPSDUHG WR UDSHVHHG PHWK\O HVWHU  YRO LQ UHIHUHQFH IXHO  ZKLFK KDG D QHJOLJLEOH LQIOXHQFHRQERWKSDUDPHWHUV *($YROLQUHIHUHQFHIXHODSSHDUVWRKDYHQRHIIHFWRQHPLVVLRQVZKHQEOHQGHG ZLWKUHIHUHQFHIXHO*%$RQWKHRWKHUKDQGZKHQSUHVHQWLQYROLQUHIHUHQFHIXHO ZDVDEOHWRUHPDUNDEO\UHGXFHWKHSDUWLFOHVHPLVVLRQVXSWRDJDLQVWOHVVWKDQZKHQ RQO\YRORIWKLVFRPSRXQGZDVEOHQGHG)RUFRPSDULVRQDSSUR[LPDWHO\RIUHGXFWLRQ RQ WKH HPLVVLRQ RI SDUWLFOH PDWWHU ZDV DFKLHYHG IRU UDSHVHHG PHWK\O HVWHU  YRO LQ UHIHUHQFHIXHO$VXPPDU\RIWKHVHUHVXOWVLVSUHVHQWHGLQ7DEOH  6 7$7(2)7+( $ 57     7DEOH²,QIOXHQFHRIEOHQGLQJJO\FHURODFHWDOVDQGUDSHVHHGPHWK\OHVWHUVZLWKGLHVHORQ SDUWLFOHPDWWHUDQG [ 12 HPLVVLRQV   *O\FHURO'HULYDWLYHYRO 5HIHUHQFH)XHO 5HIHUHQFH)XHO 3DUWLFOHV(PLVVLRQV 12 [ 3DUWLFOHV(PLVVLRQV 12 [  *($     *%$     *%$     5DSHVHHG0HWK\O(VWHU     5DSHVHHG0HWK\O(VWHU       ,QDSDWHQWRQWKHXVHRIDFHWDOVDVGLHVHOIXHODGGLWLYHVZDVSXEOLVKHG  7KLVZRUN DOVRLVVXHGWKHHIIHFWRIWKHXVHRIDFHWDOVLQWKHDPRXQWRIVROLGSROOXWDQWV HPLWWHGZLWK H[KDXVWJDVHV7KHWHVWVZHUHSHUIRUPHGLQDFFRUGDQFHZLWK(XURSHDQGLUHFWLYH&( PRGLILHG E\ WKH GLUHFWLYH (& ZKLFK FRQVLGHUV D F\FOH GHQRPLQDWHG 09(*V (XUR  WKDWFRPSULVHV DQXUEDQ SKDVH ZLWK D OHQJWK RI  NP (&(F\FOHDQGD VXEXUEDQ SKDVH NP ORQJ(8'&F\FOH8QGHUWKHVHFRQGLWLRQVZKHQLQYROXPHRI*($ZDV DGGHGWRWKHWHVWHGJDVRLODUHGXFWLRQRQSDUWLFOHVHPLVVLRQVRIZDVREVHUYHGIRU (&(DQGIRU(8'&FRPSDULQJZLWKJDVRLO(PLVVLRQVDEVROXWHYDOXHVGHWHUPLQHGZLWKLQ WKLVZRUNDUHSUHVHQWHGLQ7DEOH  7DEOH²(IIHFWRQSDUWLFOHVHPLVVLRQVRIWKHDGGLWLRQRI*($WRJDVRLO   )XHO 3DUWLFOHHPLVVLRQVJͼNP   (&(&\FOH (8'&&\FOH 09(*&\FOH *DV2LO        *DV2LO *($      0RUHRYHU GXH WR WKH SUHVHQFH RI D IUHH K\GUR[\O JURXS F\FOLF DFHWDOV PLJKW XQGHUJR WUDQVFDUERQDWLRQ UHDFWLRQV LQ RUGHU WR SURGXFH JO\FHURO DFHWDO FDUERQDWHV 7KLV UHDFWLRQ LV XVXDOO\ FDWDO\VHG E\ EDVHV DQG WKH SURGXFW FDQ DOVR EH XVHG DV IXHO DGGLWLYH SUHVHQWLQJ VLPLODUUHVXOWVWRWKRVHRIJO\FHURODFHWDOV   /LPLWDWLRQV WR WKH XVH RI JO\FHURO F\FOLF DFHWDOV DV DGGLWLYHV IRU JDVROLQH DUH PDLQO\ UHODWHGWRPLVFLELOLW\SUREOHPV7KHSUHVHQFHRIIUHHK\GUR[\OJURXSVLQWKHVHFRPSRXQGVKDV EHHQLQGLFDWHGDVWKHFDXVHIRUWKLVSKDVHLQFRPSDWLELOLW\$VROXWLRQIRUWKLVSUREOHPFRXOG FRQVLVWRQWKHDON\ODWLRQRIWKLVJURXSWKDWZRXOGDOORZUHDFKLQJVXIILFLHQWVROXELOLW\RIWKH DFHWDOLQK\GURFDUERQEDVHGIXHOVDYRLGLQJWKHLQIOXHQFHRIWKHK\GUR[\OLQWKHLQWHUDFWLRQRI WKHVHVSHFLHV$QDOWHUQDWLYHVWUDWHJ\WRRYHUFRPHWKLVSUREOHPZDVVXJJHVWHGFRQVLVWLQJLQ * /<&(52/$&(7$/6352'8&7,21%< 6 ,08/$7(' 0 29,1* % (' 5 ($&725     WKH VLPXOWDQHRXV DGGLWLRQ RI DQ DOFRKRO XVXDOO\ HWKDQRO WR WKH JDVROLQH   ,Q IDFW WKLV SURFHGXUHQRWRQO\HOLPLQDWHGWKHPLVFLELOLW\SUREOHPVRIDFHWDOVDVLWKDVSURYHGWREHDQ HIILFLHQW SURFHVV IRU LQFUHDVLQJ WKH RFWDQH QXPEHU RI WKH IXHO *($ ZDV RQH RI WKH FRPSRXQGVHYDOXDWHG$QDPRXQWRIRIWKLVDFHWDOSOXVRIHWKDQRODOOSHUFHQWDJHV E\ ZHLJKW ZHUH DGGHG WR D PRGHO PL[WXUH RI LVRRFWDQHQKHSWDQH  OHDGLQJ WR D VLJQLILFDQW LQFUHDVH RI  XQLWV LQ WKH RFWDQH QXPEHU RI WKH ILQDO IXHO FRPSRVLWLRQ )XUWKHUPRUH WKLV ZRUN DOVR PHQWLRQV WKDW WKH XVH RI WKHVH PL[WXUHV RI F\FOLF DFHWDOV DQG DOFRKROVDUHDEOHWRHQKDQFHWKHVWDELOLW\RIWKHIXHOKDYLQJDSRVLWLYHLPSDFWRQLQWHUQDO FRPEXVWLRQHQJLQHV 7KHQRWRULRXVUHVXOWVIURPWKHXVHRIF\FOLFDFHWDOVRIJO\FHURODVHQYLURQPHQWDOIULHQGO\ DGGLWLYHV SURPSWHG WKH GHYHORSPHQW RI SURFHVVHV WKDW LQWHJUDWH WKH SURGXFWLRQ RI WKHVH FRPSRXQGVVLPXOWDQHRXVO\WRELRGLHVHOSURGXFWLRQDOORZLQJWKHUHFRYHU\RIWKHJO\FHURODQG LQFUHDVLQJWKHRYHUDOOSURFHVV\LHOG$QH[DPSOHRIWKLVLVWKHSDWHQWVXEPLWWHGE\0LOOHUHW DO   SUHYLRXVO\ GLVFXVVHG 7KH SURFHVV FRQVLVWV RQD WUDQVHVWHULILFDWLRQXQLW WR SURGXFH DQ HTXLOLEULXPPL[WXUHRIELRGLHVHOJO\FHURODQGXQUHDFWHGDOFRKRODQGWULJO\FHULGHVZKLOHLQD SDUDOOHOXQLWWKHUDZPDWHULDOIRUWKHF\FOLFDFHWDODOGHK\GHRUDFHWDOLVEHLQJV\QWKHVLVHG %RWKRXWOHWVWUHDPVRIWKHVHXQLWVDUHIHGWRDGLVWLOODWLRQFROXPQ$ELRGLHVHOFRQWDLQLQJDQ DFHWDOGHULYHGIURPJO\FHUROLVREWDLQHGDVILQDOSURGXFW,QWKLVZRUNDXWKRUVGHVFULEHWKH SDUWLFXODUSURFHVVIRUWKHSURGXFWLRQRI*($DVDGGLWLYHIRUWKHELRGLHVHO$QRWKHUH[DPSOHRI LQWHJUDWHGSURGXFWLRQRIELRGLHVHODQGWKHUHVSHFWLYHF\FOLFDFHWDODGGLWLYHZDVUHSRUWHGLQ +LOOLRQHWDOSDWHQW  $VSHFLILFKHWHURJHQHRXVFDWDO\VWFRQVWLWXWHGE\DQR[LGHDQGRUDQ DOXPLQLXPR[LGHRIPHWDOVVXFKDV]LQFWLWDQLXP]LUFRQLDRUELVPXWKIRULQVWDQFHVKRXOGEH XVHG WR SURPRWH WKH WUDQVHVWHULILFDWLRQ UHDFWLRQ IRU WKH SURGXFWLRQ RI D FRQYHQWLRQDO ELRGLHVHODQGIUHHJO\FHURODVLPSXULW\7KLVJO\FHUROFRXOGWKHQEHXVHGIRUWKHV\QWKHVLVRI F\FOLFDFHWDOVDGGLWLYHVWKURXJKUHDFWLRQZLWKWKHFRUUHVSRQGHQWDOGHK\GHDQGWKHSURGXFW LVILQDOO\LQWURGXFHGLQELRGLHVHO  -HW)XHO$GGLWLYH 7KHORZWHPSHUDWXUHVIRXQGDWWKHKLJKDOWLWXGHVDWZKLFKDLUFUDIWVIO\PLJKWLQGXFHWKH IRUPDWLRQRILFHIURPWKHZDWHUGLVVROYHGLQWKHMHWIXHOZKHQLWLVORDGHGRQWRWKHDLUFUDIW ZKLFKVHSDUDWHVIURPWKHIXHODVLWVWHPSHUDWXUHGURSV7KHSUHVHQFHRILFHFU\VWDOVLQWKH IXHO OLQHV FDQ FDXVH VHYHUH SUREOHPV WKURXJK WKH UHGXFWLRQ RI IXHO IORZ WR WKH HQJLQH $OWKRXJK PRVW FRPPHUFLDO DLUFUDIWV KDYH KHDWHUV RQ WKHLU PDLQ ILOWHUV SUHYHQWLQJ LFH GHSRVLWLQJE\PHOWLQJLWPDQ\PLOLWDU\DLUFUDIWGRQRWKDYHWKRVHKHDWHUVDQGWKHUHIRUHWKH XVHRIDYLDWLRQIXHODGGLWLYHVWRDYRLGWKLVSUREOHPEHFRPHVQHFHVVDU\7KHVHDGGLWLYHVDUH FRPPRQO\ UHIHUUHG WR DV )XHO 6\VWHP ,FLQJ ,QKLELWRUV )6,, DQG FRQVLVW RQ FKHPLFDO FRPSRXQGVWKDWGLVVROYHZLWKZDWHUSUHIHUHQWLDOO\RYHUWKHMHWIXHOORZHULQJVLJQLILFDQWO\LWV IUHH]LQJSRLQWVRWKDWQRLFHFU\VWDOVDUHIRUPHG7KHVHFRPSRXQGVDUHDGGHGLQYHU\VPDOO 6 7$7(2)7+( $ 57     DPRXQWVDQGE\YROXPHRQFHWKH\DUHRQO\VOLJKWO\VROXEOHLQIXHODQGXVXDOO\ QRWDWWKHUHILQHU\EXWDWVRPHSRLQWLQWKHIXHOGLVWULEXWLRQFKDLQVLQFHWKH\IRUPDYHU\ YLVFRXVSKDVHZLWKZDWHUWKDWVHSDUDWHVIURPWKHIXHO $WWKHSUHVHQWWLPHGLHWK\OHQHJO\FROPRQRHWK\OHWKHU'L(*0(LVWKHPRVWFRPPRQO\ XVHG)6,,UHJXODWHGXQGHU0,/'7/%  LQWKH8QLWHG6WDWHVDQG'HIHQFH6WDQGDUG ,VVXH    LQ WKH 8QLWHG .LQJGRP UHSODFLQJ HWK\OHQH JO\FRO PRQRHWK\O HWKHU (*0( UHJXODWHGE\0,/,(  LQWKH8QLWHG6WDWHVRQFHLWLVOHVVWR[LFDQGKDVDKLJKHUIODVK SRLQW+RZHYHU'L(*0(UHSUHVHQWVDSHUVRQDOKD]DUGZKHQZDWHUFRQWDLQLQJWKLVFRPSRXQG LVGUDLQHGIURPWKHIXHOV\VWHPDQGDQHQYLURQPHQWDOKD]DUGVLQFHJO\FROVUHTXLUHDKLJK DPRXQW RI R[\JHQ IRU LWV GHFRPSRVLWLRQ HYHQWXDOO\ FDXVLQJ WKH GHDWK RI VRPH DTXDWLF RUJDQLVPVDVWKHZDWHUJHWVLPSRYHULVKHGLQR[\JHQIRULQVWDQFH3URS\OHQHJO\FROXVHGDVD ZLQJGHLFHUZDVVXJJHVWHGDVDQDOWHUQDWLYH)6,,EXWLWVKLJKFRVWSHUXQLWHIIHFWLYHQHVVKDV GLVFRXUDJHGLWVXVH,QDGGLWLRQWKLVFRPSRXQGLVDOVRWR[LFDOWKRXJKOHVVWKDQ'L(*0(DQG (*0( &RQVHTXHQWO\ VWXGLHV KDYH EHHQ FRQGXFWHG LQ RUGHU WR ILQG D OHVV WR[LF DQG OHVV H[SHQVLYHFRPSRXQGWREHXVHGDV)6,,*O\FHURODFHWDOVDQGNHWDOVKDYHEHHQLGHQWLILHGDV VXLWDEOHGHLFLQJDGGLWLYHVLQSUHYLRXVZRUNV  ,QWKRVHZRUNVLWLVVXJJHVWHGWKHV\QWKHVLV RI WKLV VXEVWDQFHV WKURXJK WKH UHDFWLRQ RI JO\FHURO ZLWK IRUPDOGHK\GH DFHWDOGHK\GH DQG NHWRQH IROORZHG E\ D SXULILFDWLRQ SURFHVV OHDGLQJ WR WKH IRUPDWLRQ RI GLR[RODQH PHWKDQRO PHWK\OGLR[RODQHPHWKDQRO *($ ILYH PHPEHUHGULQJ LVRPHU DQG  GLPHWK\OGLR[RODQHPHWKDQROUHVSHFWLYHO\$OOWKHJO\FHURODFHWDOVWHVWHGSUHVHQWHGD SHUIRUPDQFHDVLFLQJLQKLELWRUVLPLODUWRWKDWRI'L(*0(DQGGLSURS\OHQHJO\FRODVVKRZQLQ )LJXUH   )XUWKHUPRUH WKHVH FRPSRXQGV ZHUH WHVWHG IRU IXHO LQVWDELOLW\ DQG LQFRPSDWLELOLW\ UHDFWLRQVDFFRUGLQJWRWKH$670PHWKRG'  LQWKHMHWIXHO-3UHYHDOLQJWKDWWKLV DGGLWLYHVVKRXOGEHVWDEOHLQWKHIXHOIRUDWOHDVWRQHWRWZR\HDUVZLWKRXWLQGXFLQJVHGLPHQW IRUPDWLRQ QRU SHUR[LGDWLRQ 7KH UHVXOWV REWDLQHG IRU JO\FHURO DFHWDOV DQG NHWDOV PLJKW EH DVVRFLDWHGWRWKHSUHVHQFHRIDK\GUR[\OJURXSLQWKHVHFRPSRXQGVWKDWFRXOGERQGWRZDWHU GLVVROYHGLQWKHIXHODQGWKHDEVHQFHRIRWKHUKHWHURDWRPIXQFWLRQDOJURXSVWKDWFRXOGOHDG WR VHGLPHQWV IRUPDWLRQ 7KH EHQHILWV RI XVLQJ WKHVH VXEVWDQFHV DV DOWHUQDWLYH )6,, DUH SDUWLFXODUO\ VLJQLILFDQW ZKHQ KHDOWK DQG HQYLURQPHQWDO FRQVHTXHQFHV RI LWV XVH DUH FRQVLGHUHGLQFRPSDULVRQZLWKFRQYHQWLRQDOGHLFLQJDJHQWV 7KHXVHRIDFHWDOVDQGNHWDOVRIJO\FHURODVZLQJGHLFHULVVWLOOXQGHULQYHVWLJDWLRQ  * /<&(52/$&(7$/6352'8&7,21%< 6 ,08/$7(' 0 29,1* % (' 5 ($&725      )LJXUH     ²  7HPSHUDWXUHSURILOHDORQJWLPHIRUFXUUHQWO\XVHG)6,,DQGF\FOLFDFHWDOVIURP JO\FHURODGDSWHG     3URFHVV,QWHQVLILFDWLRQ0XOWLIXQFWLRQDO 5HDFWRUV 3URFHVV ,QWHQVLILFDWLRQ KDV EHHQ SUHVHQWHG DV WKH SDUDGLJP RI VXVWDLQDEOH SURFHVV HQJLQHHULQJDOORZLQJWRRYHUFRPHWKHHQYLURQPHQWDODQGHFRQRPLFFKDOOHQJHVRIFKHPLFDO LQGXVWU\&KHPLFDOLQGXVWULDOSURFHVVHVDUHEDVHGRQDQDVVRFLDWLRQRIVHYHUDOUHDFWLRQDQG VHSDUDWLRQ VWHSV 0RVW FRPPRQO\ HDFK LQGXVWULDO XQLW LV UHVSRQVLEOH HLWKHU IRU UHDFWLRQ RU VHSDUDWLRQ+RZHYHULQUHFHQW\HDUVWKHXVHRIK\EULGXQLWVZKHUHERWKRIWKHVHSURFHVVHV RFFXUVLPXOWDQHRXVO\LQDVLQJOHDSSDUDWXVKDVEHHQUHFRJQL]HGDVDSDUWLFXODUO\HIILFLHQW VROXWLRQIURPSURFHVVVWDQGSRLQW 7KH FRQFHSW EHKLQG WKHVH WHFKQRORJLHV LV UHODWHG WR WKH HTXLOLEULXP GLVSODFHPHQW SURPRWHGE\WKHFRQWLQXRXVUHPRYDORIRQHSURGXFWRIWKHUHDFWLRQPHGLXPZKLFKDFFRUGLQJ WR/H&KDWHOLHU·VODZZLOOUHVXOWLQDVKLIWLQJRIWKHUHDFWLRQIDYRXULQJSURGXFWVIRUPDWLRQ DQG WKHUHIRUH LQFUHDVLQJ FRQYHUVLRQ 7KLV IDFW DOORZV WKLV VRUW RI XQLWV WR EH DEOH WR RYHUFRPHWKHUPRG\QDPLFOLPLWDWLRQVWKDWDUHDVVRFLDWHGWRDQXPEHURIUHDFWLRQV 7KH SRWHQWLDO WR UHGXFH FDSLWDO LQYHVWPHQW LV JHQHUDOO\ HQGRUVHG WR PXOWLIXQFWLRQDO UHDFWRUVVLQFHLQVWHDGRIXVLQJDWOHDVWWZRXQLWVWRREWDLQWKHILQDOSURGXFWWKHLQWHJUDWHG SURFHVVZLOORQO\UHTXLUHRQH  )XUWKHUPRUHDPRQJWKHDGYDQWDJHVRIK\EULGUHDFWRUVWKH ϮϯϬ ϮϰϬ ϮϱϬ ϮϲϬ ϮϳϬ ϮϴϬ ϮϵϬ ϯϬϬ Ϭ ϭϬϬ ϮϬϬ ϯϬϬ ϰϬϬ d;<Ϳ dŝŵĞ;ŵŝŶͿ ϮͲŵĞƚŚLJůͲϭϯͲĚŝŽdžŽůĂŶĞͲϰͲŵĞƚŚĂŶŽů ĚŝĞƚŚLJůĞŶĞŐůLJĐŽůŵŽŶŽŵĞƚŚLJůĞŚƚĞƌ ϭϯͲĚŝŽdžŽůĂŶĞͲϰͲŵĞƚŚĂŶŽů ĚŝƉƌŽƉLJůĞŶĞŐůLJĐŽů 6 7$7(2)7+( $ 57     SRVVLELOLW\ WR UHGXFH HQHUJ\ FRQVXPSWLRQ LPSURYH VHOHFWLYLW\ WRZDUGV D SURGXFW DQG RYHUFRPHWKHUPRG\QDPLFOLPLWDWLRQVVXFKDVD]HRWURSHVDUHEURDGO\DFNQRZOHGJHG   $ PXOWLSOLFLW\ RI VHSDUDWLRQ SULQFLSOHV FDQ EH FRPELQHG ZLWK UHDFWLRQ GLVWLOODWLRQ FKURPDWRJUDSK\ PHPEUDQH VHSDUDWLRQ FU\VWDOOL]DWLRQ H[WUDFWLRQ SHUYDSRUDWLRQ DPRQJ RWKHUV2QHRIWKHILUVWUHSRUWHGPXOWLIXQFWLRQDOUHDFWRUVFRQVLVWHGRQDGLVWLOODWLRQFROXPQ ILOOHGZLWKDFDWDO\WLFDFWLYHSDFNLQJIRUPHWK\ODFHWDWHSURGXFWLRQ  ,QWKLVSDUWLFXODUFDVH WKHUHDFWDQWVZHUHLQWURGXFHGLQWKHGLVWLOODWLRQFROXPQZKHUHFRQYHUVLRQRYHUWKHFDWDO\VW RFFXUUHG $W WKH VDPH WLPH WKH UHDFWLRQ SURGXFWV ZHUH VHSDUDWHG E\ GLVWLOODWLRQ FRQVHTXHQWO\RYHUFRPLQJHTXLOLEULXPOLPLWDWLRQV 1HYHUWKHOHVVWR ZLWKGUDZ DOOWKH EHQHILWV RI WKH XVH RI LQWHJUDWHG UHDFWLRQ VHSDUDWLRQ SURFHVVHV D GHHS VWXG\ RI LWV SHUIRUPDQFH DQG DFFXUDWH RSWLPLVDWLRQ RI LWV RSHUDWLRQDO YDULDEOHVDQGSURFHVVGHVLJQLVUHTXLUHG 6LPXODWHG0RYLQJ%HG5HDFWRU&RQFHSWDQG$SSOLFDWLRQV &RQWLQXRXVFRXQWHUFXUUHQWFKURPDWRJUDSKLFSURFHVVHVWDNHDGYDQWDJHRIWKHGLIIHUHQFHV LQWKHDGVRUSWLRQH[LVWLQJEHWZHHQFKHPLFDOVDQGHQKDQFHWKHPWKURXJKWKHPD[LPL]DWLRQRI WKH DGVRUSWLRQ GULYLQJ IRUFH UHVXOWLQJ IURP WKH FRXQWHU FXUUHQW RSHUDWLRQ PRGH PDNLQJ LW SRVVLEOH WR SURFHHG WR VHSDUDWLRQV WKDW ZRXOG EH WRR GLIILFXOW RU LPSRVVLEOH WKURXJK WUDGLWLRQDO PHWKRGV +RZHYHU WKH LPSOHPHQWDWLRQ RI D 7UXH 0RYLQJ %HG 70% SURFHVV SUHVHQWVUHVWULFWLYHWHFKQLFDOLVVXHVUHODWHGZLWKWKHPRWLRQRIWKHVROLGDVSDUWLFOHVDEUDVLRQ GHSHQGHQFH RI WKH EXON IOXLGL]DWLRQ RQ WKH IOXLG YHORFLW\ RU EDFNPL[LQJ HIIHFWV DPRQJ RWKHUV,Q%URXJKWRQDQG*HUKROG  GHYHORSHGDQGSDWHQWHGWKH6LPXODWHG0RYLQJ%HG 60%DXQLWFRQVLVWLQJLQDVHWRILQWHUFRQQHFWHGIL[HGEHGFROXPQVFDSDEOHRIRYHUFRPLQJ WKHSUREOHPVRIWKH70%WKURXJKWKHVLPXODWLRQRIWKHVROLGPRYHPHQWE\DV\QFKURQRXVVKLIW RIDOOLQOHWDQGRXWOHWVWUHDPVSRVLWLRQLQWKHGLUHFWLRQRIWKHIOXLGIORZ2YHUWKH\HDUVWKLV WHFKQRORJ\ KDV EHHQ WKH VFRSH RI VHYHUDO UHVHDUFK ZRUNV DLPLQJ DOWHUQDWLYH RSHUDWLRQ PRGHV   GHVLJQ DQG RSWLPL]DWLRQ   DPRQJ RWKHU WHFKQLFDO DVSHFWV   DQG KDV XQGHUJRQH VLJQLILFDQW GHYHORSPHQWV PHHWLQJ WKH QHHGV RI LPSRUWDQW LQGXVWULDO SURFHVVHV 3ULPDULO\ LPSOHPHQWHG E\ 823 ,QF LQ WKH ´6RUEH[  µ SURFHVV   WKH 60% KDV EHHQ ODUJHO\ DSSOLHGLQWKHSHWURFKHPLFDOILHOGIRUWKHSXULILFDWLRQRIS[\OHQHLQWKH´3DUH[  µSURFHVV RUIRUWKHVHSDUDWLRQRIROHILQVIURPSDUDIILQVLQWKH´2OH[  µSURFHVVIRULQVWDQFH%HVLGHV WKH ODUJHVFDOH SHWURFKHPLFDO SURFHVVHV WKH 60% KDV DOVR IRXQG DSSOLFDWLRQV LQ ILQH FKHPLVWU\DQGSKDUPDFHXWLFVDVLQWKHFKLUDOVHSDUDWLRQXQLWVIURP129$6(3&RPSDQ\ )ROORZLQJ WKH SULQFLSOHV RI LQWHJUDWHG SURFHVVHV WKURXJK WKH DVVRFLDWLRQ RI WKH 60% VHSDUDWLRQSURFHVVZLWKFKHPLFDOUHDFWLRQDQHZWHFKQRORJ\GHQRPLQDWHG6LPXODWHG0RYLQJ %HG 5HDFWRU 60%5 ZDV JHQHUDWHG &RQYHQWLRQDOO\ WKH 60%5 FRQVLVWV RQ D VHW RI LQWHU FRQQHFWHGFROXPQVDVVHPEOHGLQVHULHVSDFNHGZLWKDPL[WXUHRIDFDWDO\VWDQGDVHOHFWLYH DGVRUEHQWRUDVROLGWKDWDFWVDVERWK$VLQWKH60%WKHFRXQWHUFXUUHQWPRYHPHQWRIWKH * /<&(52/$&(7$/6352'8&7,21%< 6 ,08/$7(' 0 29,1* % (' 5 ($&725     VROLGLVVLPXODWHGE\WKHV\QFKURQL]HGSHULRGLFVKLIWLQJRILQOHWVDQGRXWOHWVIRURQHFROXPQ GLVWDQFHLQWKHGLUHFWLRQRIWKHIOXLGIORZ*HQHUDOO\WKHUHDUHWZRLQOHWVWUHDPVIHHGDQG GHVRUEHQWDQGWZRRXWOHWVWUHDPVH[WUDFWDQGUDIILQDWH7KHUHDFWDQWVDUHLQWURGXFHGLQWKH XQLWWKURXJKWKHIHHGVWUHDPZKLOHWKHPRVWDQGOHDVWDGVRUEHGVSHFLHVDUHFROOHFWHGLQWKH H[WUDFWDQGUDIILQDWHUHVSHFWLYHO\7KHSRVLWLRQRIWKHLQOHWDQGRXWOHWVWUHDPVGHILQHVWKH GLYLVLRQRIWKHXQLWLQIRXUVHFWLRQV •6HFWLRQ , EHWZHHQ GHVRUEHQW DQG H[WUDFW SRUWV WKH PRUH VWURQJO\ DGVRUEHG SURGXFW GHVRUEV IURP WKH VROLG UHJHQHUDWLQJ LW )RU WKDW SXUSRVH WKH KLJKHVW IORZUDWHZLWKLQWKHXQLWLVUHTXLUHGLQWKLVVHFWLRQ •6HFWLRQ,,EHWZHHQH[WUDFWDQGIHHGSRUWVUHDFWLRQWDNHVSODFHDQGWKHPRUH VWURQJO\DGVRUEHGSURGXFWLVWUDQVSRUWHGZLWKWKHVROLGSKDVHWRZDUGVWKHH[WUDFW SRUWZKHUHLWLVZLWKGUDZQ7KHOHVVVWURQJO\DGVRUEHGSURGXFWLVWUDQVSRUWHGZLWK WKHOLTXLGLQGLUHFWLRQRIWKHUDIILQDWHSRUW •6HFWLRQ ,,, EHWZHHQ IHHG DQG UDIILQDWH SRUWV UHDFWLRQ DQG VHSDUDWLRQ RFFXU LGHQWLFDOO\ WR 6HFWLRQ ,, KRZHYHU DQ KLJKHU FRQFHQWUDWLRQ RI WKH OHVV DGVRUEHG SURGXFWLVREVHUYHGZKLFKLVFROOHFWHGLQWKHUDIILQDWHVWUHDP •6HFWLRQ ,9 EHWZHHQ UDIILQDWH DQG GHVRUEHQW SRUWV DGVRUSWLRQ RI WKH OHVV UHWDLQHG SURGXFW RFFXUV OHDGLQJ WR WKH UHJHQHUDWLRQ RI WKH GHVRUEHQW ZKLFK LV UHF\FOHGWR6HFWLRQ,  $GHVFULSWLYHVFKHPHRIWKH70%5DQGWKH60%5LVSUHVHQWHGLQ)LJXUH  D  E    )LJXUH     ²  6FKHPHRID 70%5DDQGD 60%5  E  XQLW     7KH GLIIHUHQFHV LQ WKH FRQFHQWUDWLRQ SURILOHV RI HDFK FRPSRXQG ZLWKLQ WKH XQLW DV D FRQVHTXHQFH RI WKH GLIIHUHQFHV LQ WKH DGVRUEHQW VHOHFWLYLW\ WRZDUGV HDFK RQH DUH WKH H[SODQDWLRQIRUWKH60%5VHSDUDWLRQDQGHTXLOLEULXPGLVSODFHPHQWFDSDFLWLHV+RZHYHUDQ 6 7$7(2)7+( $ 57     LPSRUWDQW UHPDUN PXVW EH DGGUHVVHG WR WKH IDFW WKDW DOWKRXJK WKH 60%5 WHFKQRORJ\ FDQ DFKLHYHFRQYHUVLRQZLWKUHFRYHU\RIWKHGHVLUHGSURGXFWVLQFHWKHRXWOHWVWUHDPV DUHGLOXWHGLQWKHGHVRUEHQWIXUWKHUVWHSVDUHQHFHVVDU\WRUHF\FOHWKHGHVRUEHQWEDFNWRWKH 60%5DQGSXULI\WKHSURGXFWV 60%5 HIIHFWLYHQHVV DQG IOH[LELOLW\ DVVXUH WKH SRWHQWLDO RI LWV DSSOLFDWLRQ LQ QXPHURXV SURFHVVHV   3DUWLFXODUO\ LQWHUHVWLQJ UHVXOWV KDYH EHHQ UHSRUWHG IRU WKH SURGXFWLRQ RI R[\JHQDWHG FRPSRXQGV GXH WR WKH SHUIRUPDQFH RI WKLV FKURPDWRJUDSKLF UHDFWRU LQ DFHWDOL]DWLRQ  HWKHULILFDWLRQ  HVWHULILFDWLRQDQGWUDQVHVWHULILFDWLRQ  UHDFWLRQVWKDW LQFOXVLYHO\ OHG WR WKH GHYHORSPHQW RI D IHZ SDWHQWHG SURFHVVHV     'HVSLWH WKH WKHUPRG\QDPLF OLPLWDWLRQV RI WKH SUHYLRXVO\ PHQWLRQHG UHDFWLRQV FRQYHUVLRQ YDOXHV RI DSSUR[LPDWHO\  ZHUH DFKLHYHG ZLWK WKH 60%5 +LJK SURGXFWV SXULW\ DERYH  LQ H[WUDFWDQGUDIILQDWHVWUHDPVZHUHDOVRSRVVLEOHWRREWDLQUHJDUGOHVVRIWKHV\VWHPVWXGLHG 7KHXVHRIWKH60%5WHFKQRORJ\LQDQDFHWDOL]DWLRQUHDFWLRQZDVILUVWDVVHVVHGE\6LOYDHW DO  WKURXJKWKHSURGXFWLRQRI'((E\UHDFWLQJHWKDQRODQGDFHWDOGHK\GH$PEHUO\VW ZDVXVHGDVVROLGSKDVHFDWDO\VWDGVRUEHQWDQGEHVLGHVEHLQJXVHGDVUHDFWDQWHWKDQROZDV DOVR XVHG DV GHVRUEHQW DJHQW 7KH EHVW H[SHULPHQWDO SHUIRUPDQFH IRU WKLV SURFHVV ZDV DFKLHYHGZKHQWKHVZLWFKLQJWLPHZDVVHWWR PLQ DQGDPL[WXUHFRQWDLQLQJLQPROHV RIDFHWDOGHK\GHZDVIHGWRWKHXQLWDW  P/ PLQ − ⋅ ZKLOHWKHUDIILQDWHZDVFROOHFWHGDW  P/ PLQ − ⋅  7KHVH H[SHULPHQWDO FRQGLWLRQV DOORZHG DQ DFHWDOGHK\GH FRQYHUVLRQ RI DSSUR[LPDWHO\  DQG D UDIILQDWH VWUHDP SXULW\ RI  7KH SURGXFWLYLW\ DQG GHVRUSWLRQ FRQVXPSWLRQ ZHUH  − − ⋅ ⋅   3URG $GV NJ / GD\  DQG   'HV 3URG / NJ − ⋅  UHVSHFWLYHO\ 6LPXODWLRQ VWXGLHVGHPRQVWUDWHGWKDWLWZRXOGEHSRVVLEOHWRLPSURYHWKHXQLWSHUIRUPDQFH$PD[LPXP SURGXFWLYLW\RI − − ⋅ ⋅   3URG $GV NJ / GD\ ZLWKDUDIILQDWHSXULW\RIZDVUHSRUWHGWRJHWKHU ZLWKDGHVRUEHQWFRQVXPSWLRQRI  'HV 3URG / NJ − ⋅  *LYHQWKHSRVLWLYHUHVXOWVREWDLQHGIRUWKH'((SURGXFWLRQLQWKH60%5WKHV\QWKHVLVRI GLPHWKR[\HWKDQH   DQG GLEXWKR[\HWKDQH   ZHUH DOVR VWXGLHG )RU WKHVH SURFHVVHVWKH UHVSHFWLYH DOFRKRO ZDV XVHG DV GHVRUEHQW DQG UHDFWHG ZLWKDFHWDOGHK\GHLQ WKH SUHVHQFH RI $PEHUO\VW $ SDUWLFXODUO\ KLJK SURGXFWLYLW\ ZDV REWDLQHG IRU  GLEXWKR[\HWKDQH7KHRSWLPL]HGYDOXHDFKLHYHGE\VLPXODWLRQZDV − − ⋅ ⋅   3URG $GV NJ / GD\    &RQFOXVLRQ 7KHELEOLRJUDSKLFUHVHDUFKSUHVHQWHGLQWKLV&KDSWHUDOORZHGWKHLGHQWLILFDWLRQRI*($DV DKLJKDGGHGYDOXHSURGXFW7KHHQYLURQPHQWDOEHQHILWVRIWKLVDFHWDODUHQRWRQO\UHODWHG * /<&(52/$&(7$/6352'8&7,21%< 6 ,08/$7(' 0 29,1* % (' 5 ($&725     ZLWKLWVSURGXFWLRQSURFHVVPDNLQJXVHRIUHQHZDEOHIHHGVWRFNDQGSUHVHQWLQJLWVHOIDVDQ DX[LOLDU\SURFHVVIRUWKHFRQVXPSWLRQRIWKHH[FHVVRIJO\FHUROJHQHUDWHGE\WKHLQFUHDVLQJ ELRGLHVHOSURGXFWLRQEXWDOVRZLWKLWVSRWHQWLDOILQDODSSOLFDWLRQDVDIXHODGGLWLYHZKLFKLV H[SHFWHGWRUHGXFHSDUWLFXODWHDQGJUHHQKRXVHJDVHPLVVLRQV 3URFHVV LQWHQVLILFDWLRQ KDV EHHQ UHSRUWHG DV RQH RI WKH PRVW LQQRYDWLYH DQG HIILFLHQW DGYDQFHVLQSURFHVVHQJLQHHULQJ$PRQJVWWKHGLYHUVHLQWHJUDWHGSURGXFWLRQXQLWVGHYHORSHG WKH60%5KDVVWRRGRXWE\LWVXQLTXHIOH[LELOLW\DQGSHUIRUPDQFH)URPWKHUHVXOWVSUHVHQWHG E\WKLVWHFKQRORJ\RQWKHSURGXFWLRQRIVHYHUDOR[\JHQDWHGFRPSRXQGVLQSDUWLFXODUDFHWDOV RQHFDQH[SHFWLWVVXFFHVVIXODSSOLFDWLRQLQWKHV\QWKHVLVRI*($ 7KHUHIRUH LW FDQ EH FRQFOXGHG WKDW WKH SURGXFWLRQ RI *($ E\ 60%5 LQWHQGHG WR EH DFKLHYHGWKURXJKWKHZRUNGHYHORSHGLQWKLVGLVVHUWDWLRQLVIUDPHGZLWKLQWKHSULQFLSOHVRID ELREDVHGHFRQRP\SURSRVLQJWKHLPSOHPHQWDWLRQRI´JUHHQHUµSURFHVVHVLQLQWHJUDWHGELR UHILQHULHV   1RWDWLRQ $EEUHYLDWLRQV $670 $PHULFDQ6RFLHW\IRU7HVWLQJDQG0DWHULDOV '(( GLHWKR[\HWKDQH 'L(*0( 'LHWK\OHQH*O\FRO0RQRHWK\O(WKHU (&( (FRQRPLF&RPPLVVLRQIRU(XURSH (*0( (WK\OHQH*O\FRO0RQRHWK\O(WKHU (8'& ([WUD8UEDQ'ULYLQJ&\FOH (XUR%LR5HI (852SHDQ PXOWLOHYHO LQWHJUDWHG %,25()LQHU\ GHVLJQ IRU VXVWDLQDEOH ELRPDVV SURFHVVLQJ )6,, )XHO6\VWHP,FLQJ,QKLELWRUV *%$ *O\FHURO%XW\O$FHWDO *& *DV&KURPDWRJUDSKHU *($ *O\FHURO(WK\O$FHWDO )$( )DWW\$FLG(VWHU )$(( )DWW\$FLG(WK\O(VWHU /'  0HGLDQ/HWKDO'RVH /65( /DERUDWRU\RI6HSDUDWLRQDQG5HDFWLRQ(QJLQHHULQJ 0,/ 8QLWHG6WDWHV0LOLWDU\6SHFLILFDWLRQ 06', 0D[LPL]HG6XUYH\GHULYHG'DLO\,QWDNH 6 7$7(2)7+( $ 57     P7$0', 0RGLILHG7KHRUHWLFDO$GGHG0D[LPXP'DLO\,QWDNH 09(* 0RWRU9HKLFOH(PLVVLRQV*URXS 1)3$ 1DWLRQDO)LUH3URWHFWLRQ$JHQF\ 2(&' 2UJDQLVDWLRQIRU(FRQRPLF&RRSHUDWLRQDQG'HYHORSPHQW 376$ S7ROXHQHVXOIRQLF$FLG 60% 6LPXODWHG0RYLQJ%HG 60%5 6LPXODWHG0RYLQJ%HG5HDFWRU 7&' 7KHUPDO&RQGXFWLYLW\'HWHFWRU 81,)$& 8QLYHUVDO)XQFWLRQDO$FWLYLW\&RHIILFLHQW   5HIHUHQFHV  ,QWHUQDWLRQDO (QHUJ\ 2XWORRN  86 (QHUJ\ ,QIRUPDWLRQ $GPLQLVWUDWLRQ ZZZHLDJRYIRUHFDVWVLHRSGISGIDFFHVVHGLQ6HSWHPEHU  3DQZDU 1/ 6& .DXVKLN DQG 6 .RWKDUL 5ROH RI UHQHZDEOH HQHUJ\ VRXUFHV LQ HQYLURQPHQWDO SURWHFWLRQ $ UHYLHZ 5HQHZDEOH DQG 6XVWDLQDEOH (QHUJ\ 5HYLHZV S  .UDORYD,DQG-6M|EORP%LRIXHOV²5HQHZDEOH(QHUJ\6RXUFHV$5HYLHZ-RXUQDORI 'LVSHUVLRQ6FLHQFHDQG7HFKQRORJ\S  :HLODQG3%LRJDVSURGXFWLRQFXUUHQWVWDWHDQGSHUVSHFWLYHV$SSOLHG0LFURELRORJ\ DQG%LRWHFKQRORJ\S  'HPLUEDV$3ROLWLFDOHFRQRPLFDQGHQYLURQPHQWDOLPSDFWVRIELRIXHOV$UHYLHZ $SSOLHG(QHUJ\6XSSOHPHQWS66  <XVXI11$16..DPDUXGLQDQG=<DDNXE2YHUYLHZRQWKHFXUUHQWWUHQGVLQ ELRGLHVHOSURGXFWLRQ(QHUJ\&RQYHUVLRQDQG0DQDJHPHQWS  6RUGD * 0 %DQVH DQG & .HPIHUW $Q RYHUYLHZ RI ELRIXHO SROLFLHV DFURVV WKH ZRUOG(QHUJ\3ROLF\S  'HPLUEDV 0) DQG 0 %DODW 5HFHQW DGYDQFHV RQ WKH SURGXFWLRQ DQG XWLOL]DWLRQ WUHQGVRIELRIXHOV$JOREDOSHUVSHFWLYH(QHUJ\&RQYHUVLRQDQG0DQDJHPHQW ²S  3UDPDQLN 7 DQG 6 7ULSDWKL %LRGLHVHO &OHDQ IXHO RI WKH IXWXUH 1HZ SURFHVVLQJ WHFKQRORJLHV XQFRYHU PHDQV WR SURGXFH ORZVXOIXU ELRPDVVEDVHG GLHVHO +\GURFDUERQ3URFHVVLQJS  5LEHLUR 10 $& 3LQWR &0 4XLQWHOOD *2 GD 5RFKD /6* 7HL[HLUD //1 *XDULHLUR 0 GR &DUPR 5DQJHO 0&& 9HORVR 0-& 5H]HQGH 5 6HUSD GD &UX] $0GH2OLYHLUD($7RUUHVDQG-%GH$QGUDGH7KH5ROHRI$GGLWLYHVIRU'LHVHO DQG 'LHVHO %OHQGHG (WKDQRO RU %LRGLHVHO )XHOV࣯ $ 5HYLHZ (QHUJ\  )XHOV  S  6FKDUOHPDQQ -3: DQG :) /DXUDQFH (QYLURQPHQWDO VFLHQFH +RZ JUHHQ DUH ELRIXHOV"6FLHQFHS  8OJLDWL 6 $ &RPSUHKHQVLYH (QHUJ\ DQG (FRQRPLF $VVHVVPHQW RI %LRIXHOV :KHQ ´*UHHQµ,V1RW(QRXJK&ULWLFDO5HYLHZVLQ3ODQW6FLHQFHVS  +LOO-(1HOVRQ'7LOPDQ63RODVN\DQG'7LIIDQ\(QYLURQPHQWDOHFRQRPLF DQG HQHUJHWLF FRVWV DQG EHQHILWV RI ELRGLHVHO DQG HWKDQRO ELRIXHOV 3URFHHGLQJV RI WKH1DWLRQDO$FDGHP\RI6FLHQFHVS  .HOORZD\ $ DQG 3 'DRXWLGLV 3URFHVV 6\QWKHVLV RI %LRUHILQHULHV 2SWLPL]DWLRQ RI %LRPDVV &RQYHUVLRQ WR )XHOV DQG &KHPLFDOV ,QGXVWULDO  (QJLQHHULQJ &KHPLVWU\ 5HVHDUFK      &KDSWHU 7KHUPRG\QDPLFDQG.LQHWLF 6WXG\RI*($6\QWKHVLVWKURXJKDQ $FHWDOL]DWLRQ5HDFWLRQ  $'$37(' )520 )DULD 539 3HUHLUD &60 6LOYD 9070 /RXUHLUR -0 5RGULJXHV$(*O\FHURO9DORUL]DWLRQDV%LRIXHO7KHUPRG\QDPLFDQG.LQHWLF6WXG\RIWKH $FHWDOL]DWLRQ RI *O\FHURO ZLWK $FHWDOGHK\GH ,QGXVWULDO  (QJLQHHULQJ &KHPLVWU\ 5HVHDUFK S    ,QWURGXFWLRQ *O\FHURO (WK\O $FHWDO *($ LV DQ LVRPHULF PL[WXUH FRPSRVHG E\ WKH ILYH DQG VL[ PHPEHUHG ULQJ DFHWDOV K\GUR[\PHWK\OGLR[DQH DQG K\GUR[\PHWK\OPHWK\O GLR[RODQHUHVSHFWLYHO\%RWKLVRPHUVDVVXPHFLVDQGWUDQVFRQILJXUDWLRQV*HQHUDOO\*($LV V\QWKHVL]HG E\ WKH GLUHFW DFHWDOL]DWLRQ RI JO\FHURO ZLWK DFHWDOGHK\GH   RU E\ WKH WUDQVDFHWDOL]DWLRQ RI GLHWKR[\HWKDQH '(( ZLWK JO\FHURO   7KH GLUHFW DFHWDOL]DWLRQ URXWHSUHVHQWVDEHWWHUUHDFWLRQPDVVHIILFLHQF\  WKDQWKHWUDQVDFHWDOL]DWLRQDQGGHSHQGVRQ IHHGVWRFN WKDW FDQ EH REWDLQHG H[FOXVLYHO\ IURP ELRPDVV JO\FHURO LV D E\SURGXFW IURP ELRGLHVHO SURGXFWLRQ   DQG DFHWDOGHK\GH LV SURGXFHG IURP ELRHWKDQRO   7R SURFHHG WR WKH WUDQVDFHWDOL]DWLRQRI'((WKHVDPHIHHGVWRFNFRXOGEHXVHGKRZHYHUDQDGGLWLRQDOUHDFWLRQ VWHSZRXOGEHUHTXLUHGIRUWKHV\QWKHVLVRIWKHSUHFXUVRUDFHWDOIROORZHGE\DXQLWWRSURFHHG WR LWV VHSDUDWLRQ IURP WKH XQUHDFWHG FRPSRXQGV DQG E\SURGXFWV 2Q WKH RWKHU KDQG WKH 7 +(502'<1$0,&$1' . ,1(7,& 6 78'<2) *($  6 <17+(6,67+528*+$1 $ &(7$/,=$7,21 5 ($&7,21     PDMRUGUDZEDFNRIWKHDFHWDOL]DWLRQUHDFWLRQVLVWKHIRUPDWLRQRIZDWHUZKLFKLVXQGHVLUDEOH LQ VRPH *($ ILQDO DSSOLFDWLRQV LQFOXGLQJ LWV XVH DV IXHO DGGLWLYH 1HYHUWKHOHVV ZDWHUIUHH *($FDQEHREWDLQHGE\WKHXVHRIDQLQWHJUDWHGUHDFWLRQîVHSDUDWLRQWHFKQRORJ\VXFKDVWKH VLPXODWHGPRYLQJEHGUHDFWRUZKLFKKDVDOUHDG\SURYHGWREHHIILFLHQWLQRWKHUDFHWDOL]DWLRQ SURFHVVHV   )RU WKHVH UHDVRQV WKH DFHWDOL]DWLRQ ZLOO EH WKH DGRSWHG SDWKZD\ IRU WKH V\QWKHVLVRI*($LQWKHSUHVHQWZRUN 7KHPHFKDQLVPSURSRVHG  IRUWKHUHDFWLRQEHWZHHQJO\FHURODQGDFHWDOGHK\GHFRPSULVHV WKH IRUPDWLRQ RI DQ KHPLDFHWDO IURP D JO\FHURO SULPDU\ RU VHFRQGDU\ K\GUR[\O JURXS FRQVLGHUHG WKH OLPLWLQJ VWHS DQG LWV GHK\GUDWLRQ IRUPLQJ D FDUERFDWLRQ WKDW WKURXJK D QXFOHRSKLOLFVXEVWLWXWLRQPHFKDQLVP61ZLWKDQR[\JHQIURPRQHRIWKHUHPDLQLQJK\GUR[\O JURXSVRIWKHJO\FHUROPROHFXOHOHDGVWRWKHFORVXUHRIWKHKHWHURDWRPULQJWKHUHE\IRUPLQJ WKHF\FOLFDFHWDO'HSHQGLQJRQZKLFKK\GUR[\OJURXSSULPDU\RUVHFRQGDU\LVLQYROYHGLQ HDFKVWHSWKHSURGXFWRIWKHUHDFWLRQPLJKWEHWKHVL[RUILYHPHPEHUHGULQJLVRPHU $FHWDOL]DWLRQV DUH H[RWKHUPLF UHDFWLRQV WKDW SUHVHQW VLJQLILFDQW WKHUPRG\QDPLF OLPLWDWLRQV  6HYHUDODFLGFDWDO\VWVKDYHDOUHDG\EHHQDSSOLHGWRWKLVW\SHRIUHDFWLRQVRYHUD ZLGHUDQJHRIRSHUDWLQJFRQGLWLRQV7DEOHSUHVHQWVDQRYHUYLHZRIWKHGLIIHUHQWFDWDO\VWV XVHGLQDFHWDOL]DWLRQV    7DEOH²/LWHUDWXUHUHYLHZRIFDWDO\VWVXVHGLQDFHWDOL]DWLRQUHDFWLRQV $FLG&DWDO\VLV &DWDO\VW &RQGLWLRQV 7LPHK <LHOG +RPRJHQHRXV FDWDO\VWV &KORULGULFDFLG   5HDFWDQWVQKHSWDQDOJO\FHUROPRO &DWDO\VWPROPRO 7HPSHUDWXUH. 6ROYHQWGLR[DQHPROPRO   S7ROXHQHVXOIRQLF DFLG   5HDFWDQWVJO\FHUROIRUPDOGHK\GHPRO &DWDO\VWPROPRO 7HPSHUDWXUH. 6ROYHQW6ROYHQWIUHH   ,RQ([FKDQJH 5HVLQV $PEHUO\VW   5HDFWDQWVJO\FHUROEXWDQDOPRO &DWDO\VWPP 7HPSHUDWXUH. 6ROYHQWGLPHWK\OVXOIR[LGHPP   $PEHUO\VW   5HDFWDQWVIRUPDOGHK\GHJO\FHUROPRO &DWDO\VWPP 7HPSHUDWXUH. 6ROYHQW&KORURIRUPPROPRO   * /<&(52/$&(7$/6352'8&7,21%< 6 ,08/$7(' 0 29,1* % (' 5 ($&725     $FLG&DWDO\VLV &DWDO\VW &RQGLWLRQV 7LPHK <LHOG =HROLWHV +6=   5HDFWDQWV6WDQRORQHHWK\OHQHJO\FROPRO &DWDO\VWPP 7HPSHUDWXUH1$ 6ROYHQW7ROXHQHPROPRO   =60   5HDFWDQWVJO\FHUROIRUPDOGHK\GHPRO &DWDO\VWPP 7HPSHUDWXUH. 6ROYHQW6ROYHQWIUHH   6LOLFDEDVHG 0HVRSRURXV 0DWHULDOV 0R2  6L2   5HDFWDQWVQKHSWDQDOJO\FHUROPRO &DWDO\VWPP 7HPSHUDWXUH. 6ROYHQW7ROXHQHPROPRO   0&0   5HDFWDQWVEHQ]DOGHK\GHPHWKDQROPRO &DWDO\VWPP 5RRPWHPSHUDWXUH 6ROYHQW6ROYHQWIUHH   /HZLVDFLG $X&O   5HDFWDQWVQKHSWDQDOJO\FHURO &DWDO\VWPROPRO 7HPSHUDWXUH. 6ROYHQWGLR[DQHPROPRO   ,RQLFOLTXLG >+PLP@  3:  2   5HDFWDQWVSURSDQDOJO\FRO &DWDO\VWPROPRO 7HPSHUDWXUH1$ 6ROYHQW7ROXHQHPP   &OD\0LQHUDOV 0RQWPRULOORQLWH .   5HDFWDQWVEHQ]DOGHK\GHJO\FHUROPRO &DWDO\VWPP 7HPSHUDWXUH1$ 6ROYHQW&KORURIRUPPROPRO    7KHEHQHILWVRIKHWHURJHQHRXVFDWDO\VLVRYHUKRPRJHQHRXVFDWDO\VLVDUHZHOONQRZQDQG DUHPDLQO\UHODWHGZLWKWKHHDVHRIVHSDUDWLRQDQG SXULILFDWLRQRIWKHGHVLUHGSURGXFWDQG WKH DEVHQFH RI WKH QHHG IRU QHXWUDOL]DWLRQ VWHSV $PRQJ WKH KHWHURJHQHRXV FDWDO\VWV PHQWLRQHGDOXPLQRVLOLFDWHVVXFKDV]HROLWHVSUHVHQWJRRGSHUIRUPDQFHVKRZHYHUDFLGLRQ H[FKDQJH UHVLQV KDYH GHPRQVWUDWHG WR EH SDUWLFXODUO\ HIIHFWLYH IRU WKLV W\SH RI UHDFWLRQ DFKLHYLQJ KLJKHU \LHOGV DSSUR[LPDWHO\  LQ VKRUW SHULRGV RI WLPH   )XUWKHUPRUH WKHVH W\SHRIFDWDO\VWVKDYHEHHQVSHFLILFDOO\DSSOLHGLQWKHUHDFWLRQRIJO\FHUROZLWKVHYHUDOOLQHDU FKDLQDOGHK\GHV  ZLWKFRQVLGHUDEOHVXFFHVV 7KHNLQHWLFVRIDFHWDOL]DWLRQDQGWUDQVDFHWDOL]DWLRQUHDFWLRQVIRUWKHV\QWKHVLVRIJO\FHURO DFHWDOV FDWDO\VHG E\ LRQ H[FKDQJH UHVLQV KDV EHHQ GHVFULEHG E\ WKH SVHXGRKRPRJHQHRXV 7 +(502'<1$0,&$1' . ,1(7,& 6 78'<2) *($  6 <17+(6,67+528*+$1 $ &(7$/,=$7,21 5 ($&7,21     UHDFWLRQUDWHODZLQPRVWRIWKHUHSRUWHGZRUNV  2QWKHRWKHUKDQGWKHIRUPDWLRQRI JO\FHURO NHWDOV IRU LQVWDQFH WKURXJK WKH UHDFWLRQ EHWZHHQ JO\FHURO DQG DFHWRQH ZDV GHVFULEHG E\ D /DQJPXLU+LQVKHOZRRG+RXJHQ:DWVRQ EDVHG PRGHO   +RZHYHU VLPLODU UHDFWLRQ DFWLYDWLRQ HQHUJLHV ZHUH HVWLPDWHG IRU DOO SUHYLRXVO\ FLWHG ZRUNV ZLWK YDOXHV FRPSULVHGEHWZHHQ  NPRO − ⋅DQG  NPRO − ⋅ ,QWKHSUHVHQWFKDSWHUDFRPSUHKHQVLYHVWXG\RIWKHDFHWDOL]DWLRQUHDFWLRQOHDGLQJWRWKH V\QWKHVLVRI*($ZDVGHYHORSHG6LJQLILFDQWWKHUPRG\QDPLFHTXLOLEULXPGDWDZDVFROOHFWHG 7KURXJKWKHGHSHQGHQFHRIWKHFKHPLFDOHTXLOLEULXPFRQVWDQWRQWHPSHUDWXUHWKHUHDFWLRQ VWDQGDUG *LEEV IUHH HQHUJ\ DQG HQWKDOS\ ZHUH GHWHUPLQHG FRQVLGHULQJ D QRQLGHDO OLTXLG SKDVH UHDFWLRQ DQG FRPSXWLQJ WKH DFWLYLW\ RI HDFK VSHFLHV WKURXJK WKH 81,)$& JURXS FRQWULEXWLRQ PHWKRG $Q H[WHQVLYH VFUHHQLQJ RI FRPPHUFLDO FDWDO\VWV JDWKHUHG IURP D OLWHUDWXUH UHYLHZ RQ DFHWDOL]DWLRQV ZDV SHUIRUPHG  2QFH WKH PRVW VXLWDEOH FDWDO\VW ZDV VHOHFWHGWKHHIIHFWVRIVHYHUDOYDULDEOHVRQWKHUHDFWLRQUDWHZHUHH[SHULPHQWDOO\HYDOXDWHG ZLWKWKHSXUSRVHRIILQGLQJDPRGHOWKDWFRXOGEHDEOHWRSURYLGHDQDFFXUDWHGHVFULSWLRQRI WKH UHDFWLRQ NLQHWLFV RYHU D ZLGH UDQJH RI RSHUDWLQJ FRQGLWLRQV 7KH SVHXGRKRPRJHQHRXV DQG/DQJPXLUî+LQVKHOZRRGî+RXJHQî:DWVRQUHDFWLRQUDWHODZVZHUHDVVHVVHGFRQVLGHULQJWKH HIIHFWRIWKHUHDFWLRQVSHFLHVGLIIXVLRQPHFKDQLVPVLQVLGHWKHFDWDO\VWSDUWLFOHV   ([SHULPHQWDO'HVFULSWLRQ &KHPLFDOVDQG&DWDO\VWV 7KHFKHPLFDOVXVHGZHUHSURSDQRO!EXWDQRO!DFHWDOGHK\GH! DQGJO\FHURO!LQZDWHUIURP6LJPD$OGULFK'RUVHW8. 6HYHUDO FRPPHUFLDO VWURQJDFLG LRQH[FKDQJH UHVLQV 5RKP  +DDV ZHUH WHVWHG DV FDWDO\VWV7DEOHSUHVHQWVWKHLUEULHIFKDUDFWHUL]DWLRQ  * /<&(52/$&(7$/6352'8&7,21%< 6 ,08/$7(' 0 29,1* % (' 5 ($&725     7DEOH,RQ([FKDQJH5HVLQVWHVWHGLQFDWDO\VWVFUHHQLQJH[SHULPHQWV ,RQH[FKDQJH UHVLQ 7\SH 3K\VLFDO )RUP 3DUWLFOH6L]H PP ,RQ([FKDQJH &DSDFLW\HTNJ 6XUIDFH $UHDP   $PEHUO\VW:HW6WURQJDFLG 2SDTXH EHDGV ²   $PEHUO\VW:HW6WURQJDFLG 2SDTXH EHDGV ²   $PEHUO\VW:HW6WURQJDFLG 2SDTXH EHDGV    $PEHUO\VW:HW6WURQJDFLG 2SDTXH EHDGV 1$   $PEHUO\VW:HW6WURQJDFLG 2SDTXH EHDGV 1$ 1$ 1$ $PEHUO\VW:HW6WURQJDFLG 2SDTXH EHDGV    $PEHUO\VW&+ :HW6WURQJDFLG 2SDTXH EHDGV ²   1DILRQ6$&6WURQJDFLG *UDQXOHV PHVK    3ULRUWRLWVXVHWKHUHVLQZDVZDVKHGVHYHUDOWLPHVZLWKGHLRQL]HGZDWHUWKHQZDVKHG ZLWKHWKDQRODQGILQDOO\GULHGDW . XQWLOWKHPDVVUHPDLQHGFRQVWDQW7KLVSURFHGXUHZDV DGRSWHGLQRUGHUWRDYRLGDQ\GHFUHDVHRIWKHUHDFWLRQUDWHSURPRWHGE\WKHDGVRUSWLRQRI ZDWHURQHRIWKHUHDFWLRQSURGXFWVRQWKHFDWDO\VWVXUIDFH =HROLWHV+%($+0),+025DQG0ROHFXODU6LHYH$VXSSOLHGE\6G&KHPLH ZHUH DOVR WHVWHG DV FDWDO\VWV ZLWK DQG ZLWKRXW SUHYLRXV FRQGLWLRQLQJ 7KH FRQGLWLRQLQJ FRQVLVWHGRIVHYHUDOZDVKHVZLWKHWKDQROIROORZHGE\ K RIFDOFLQDWLRQDW .  ([SHULPHQWDO6HWXSDQG3URFHGXUH 7KHUPRG\QDPLF(TXLOLEULXP 7KHUPRG\QDPLF HTXLOLEULXP H[SHULPHQWV ZHUH FDUULHG RXW LQ D  P/  VWDLQOHVV VWHHO EDWFKUHDFWRUHTXLSSHGZLWKWHPSHUDWXUHDQGSUHVVXUHVHQVRUV+HDWZDVSURYLGHGWKURXJKD KHDWLQJ SODWH ZLWK H[WHUQDO WHPSHUDWXUH FRQWURO RI WKH UHDFWLRQ PHGLD $ FRQQHFWLRQ WR D KHOLXPSUHVVXUL]HGOLQHDOORZHGSUHVVXUHFRQWURO)LJXUH  7 +(502'<1$0,&$1' . ,1(7,& 6 78'<2) *($  6 <17+(6,67+528*+$1 $ &(7$/,=$7,21 5 ($&7,21      )LJXUH       6HW  XSXVHGIRUWKHUPRG\QDPLFHTXLOLEULXPH[SHULPHQWV   ([SHULPHQWV ZHUH SHUIRUPHG DW WHPSHUDWXUHV ZLWKLQ WKH UDQJH RI  .  WR  .  7R NHHSWKHUHDFWLRQPL[WXUHLQWKHOLTXLGSKDVHRYHUWKHZKROHRSHUDWLQJWHPSHUDWXUHUDQJH WKHSUHVVXUHZDVVHWWR EDU ZLWKKHOLXP'LIIHUHQWLQLWLDOFRPSRVLWLRQVZHUHWHVWHG7KH UHDFWLRQVSURFHHGHGXQWLOQRIXUWKHUFKDQJHVLQWKHFRPSRVLWLRQZHUHGHWHFWHG  &DWDO\VW6FUHHQLQJ 5HDFWLRQVZHUHFDUULHGRXWLQDJODVV P/ FORVHGYHVVHORSHUDWLQJLQEDWFKPRGHDW DWPRVSKHULF SUHVVXUH 6DPSOHV ZHUH FROOHFWHG ZLWK D V\ULQJH WKURXJK D VDPSOLQJ WXEH LPPHUVHG LQ WKH UHDFWLRQ PHGLXP 7KH PL[WXUH ZDV VWLUUHG DQG NHSW DW . ZLWK D WKHUPRVWDWLFZDWHUEDWK(TXLPRODUPL[WXUHVRIJO\FHURODQGDFHWDOGHK\GHDSSUR[LPDWHO\ P/ ZHUHSUHSDUHGDQGWKHUHDFWLRQVZHUHFDUULHGRXWLQWKHSUHVHQFHRIDFDWDO\VWZHLJKW SHUFHQWDJHRIUHODWLYHWRWKHWRWDOPDVVDW EDU )RUWKHVHFRQGLWLRQVYDSRXUîOLTXLG HTXLOLEULXP 9/( FDOFXODWLRQV VKRZHG WKDW WKH WRWDO QXPEHU RI PROHV LQ WKH YDSRXU SKDVH UHSUHVHQWHGRIWKHQXPEHURIPROHVLQWKHOLTXLGSKDVHDQGRIWKHQXPEHURIPROHV LQWKHJDVSKDVHDERYHWKHOLTXLGZDVDFHWDOGHK\GH 7KH FDWDO\VWV WKDW SUHVHQWHG WKH EHVW SHUIRUPDQFHV LQ WKH LQLWLDO H[SHULPHQWV ZHUH IXUWKHUWHVWHGRQDJODVVMDFNHWHG / FORVHGYHVVHO%FKL/DERUDWRU\(TXLSPHQW)ODZLO 6ZLW]HUODQGRSHUDWLQJLQEDWFKPRGHHTXLSSHGZLWKSUHVVXUHDQGWHPSHUDWXUHVHQVRUVDQG DEORZRIIYDOYH)LJXUHDQGPHFKDQLFDOO\VWLUUHGDW USP 7KHWHPSHUDWXUHZDVNHSW DW . WKURXJKDZDWHUEDWK/$8'$/DXGD.|QLJVKRIHQ*HUPDQ\7KHSUHVVXUHZDVVHW WR EDU WRNHHSWKHUHDFWLRQPL[WXUHLQWKHOLTXLGSKDVH  * /<&(52/$&(7$/6352'8&7,21%< 6 ,08/$7(' 0 29,1* % (' 5 ($&725       )LJXUH       6FKHPHRIWKHVHW  XSXVHGIRUNLQHWLFH[SHULPHQWV   5HDFWLRQ.LQHWLFV 7KHNLQHWLFVWXGLHVZHUHFDUULHGRXWLQWKHUHDFWLRQVHWXSSUHVHQWHGLQ)LJXUH7KH HIIHFWV RI SDUDPHWHUV VXFK DV VWLUULQJ VSHHG  USP î USP  FDWDO\VW DYHUDJH SDUWLFOH GLDPHWHU P µ DQG P µ DQGORDGLQJ  ZW DQG  ZW RIWKHWRWDOPDVVRIWKH UHDFWLRQPHGLXPWHPSHUDWXUH . î . DQGLQLWLDOFRPSRVLWLRQZHUHHYDOXDWHG7KH SUHVVXUHZDVVHWWR EDU ZLWKKHOLXPWRNHHSDOORIWKHFRPSRXQGVLQWKHOLTXLGSKDVH 7KH YDSRXU SUHVVXUHV RI DFHWDOGHK\GH DQG JO\FHURO DUH  EDU  DQG DSSUR[LPDWHO\ ]HUR UHVSHFWLYHO\ DW  .  ZKLFK ZDV WKH KLJKHVW WHPSHUDWXUH VWXGLHG $W  EDU  IRU DQ HTXLPRODU PL[WXUH RI DFHWDOGHK\GH DQG JO\FHURO DSSUR[LPDWHO\  P/  9/( FDOFXODWLRQV VKRZHGWKDWWKHWRWDOQXPEHURIPROHVLQWKHYDSRXUSKDVHZDVRIWKHWRWDOQXPEHURI PROHVLQWKHOLTXLGSKDVHDQGWKDWRIWKHJDVZDVKHOLXP 7KHRSHUDWLQJFRQGLWLRQVIRUHDFKH[SHULPHQWDUHVXPPDUL]HGLQ7DEOH  7 +(502'<1$0,&$1' . ,1(7,& 6 78'<2) *($  6 <17+(6,67+528*+$1 $ &(7$/,=$7,21 5 ($&7,21     7DEOH.LQHWLFH[SHULPHQWVRSHUDWLQJFRQGLWLRQV  7HPSHUDWXUH . ,QLWLDOPRODU UDWLR &DW/RDGLQJ ZW 3UHVVXUH EDU &DW3DUWLFOH VL]HP                                                                     ,QLWLDOUHDFWLRQPL[WXUHFRQWDLQHGZDWHUDQG*($ ,QLWLDOUHDFWLRQPL[WXUHFRQWDLQHGZDWHUDQG*($ $QDO\WLFDO0HWKRGV $OO VDPSOHV ZHUH DQDO\VHG LQ D JDV FKURPDWRJUDSK 6KLPDG]X *&  3OXV XVLQJ  SURSDQRO DV WKH VROYHQW DQG EXWDQRO DV WKH LQWHUQDO VWDQGDUG 7KH FRPSRXQGV ZHUH VHSDUDWHGXVLQJDVLOLFDFDSLOODU\FROXPQ&3:D[&% P ù PP LGILOPWKLFNQHVVRI  P µ  DQG TXDQWLILHG E\ D WKHUPDO FRQGXFWLYLW\ GHWHFWRU +HOLXP 1 ZDV XVHG DV WKH FDUULHU JDV DW D IORZ UDWH RI   P/ PLQ − ⋅  7KH WHPSHUDWXUHV RI WKH LQMHFWRU DQG WKHUPDO FRQGXFWLYLW\GHWHFWRUZHUHVHWWR . 7KHLQLWLDOFROXPQWHPSHUDWXUHZDV . IRU PLQ  WKH WHPSHUDWXUH ZDV WKHQ LQFUHDVHG DW   . PLQ − ⋅  WR  . DQG VXEVHTXHQWO\ KHOG FRQVWDQWIRUWKHIROORZLQJ PLQ    7KHUPRG\QDPLF(TXLOLEULXP &RQVLGHULQJ WKH JOREDO H[SUHVVLRQ IRU WKH QRQLGHDO OLTXLGSKDVH UHDFWLRQ EHWZHHQ DFHWDOGHK\GHDQGJO\FHUROSUHVHQWHGLQHTXDWLRQWKHFKHPLFDOHTXLOLEULXPFRQVWDQWIRU WKLV UHDFWLRQ HT .  FDQ EH H[SUHVVHG DV D IXQFWLRQ RI WKH DFWLYLWLHV RI ERWK UHDFWDQWV DQG SURGXFWVDFFRUGLQJWRHTXDWLRQ * /<&(52/$&(7$/6352'8&7,21%< 6 ,08/$7(' 0 29,1* % (' 5 ($&725     i GEA W GEA W GEA W eq i i Ac Gly Ac Gly Ac Gly a a x x K a a a x x ν γ γ γ γ = = = ∏    ZKHUH L D LVWKHDFWLYLW\RIFRPSRXQG L  L ν LVWKHVWRLFKLRPHWULFFRHIILFLHQWRIFRPSRXQG L LQWKHUHDFWLRQ L [ LVWKHPRODUIUDFWLRQRIFRPSRXQG L DQG L γ LVWKHDFWLYLW\FRHIILFLHQW RIFRPSRXQG L  )RU WKH FRPSXWDWLRQ RI WKH DFWLYLW\ FRHIILFLHQWV WKH XQLYHUVDO IXQFWLRQDO DFWLYLW\ FRHIILFLHQW81,)$&PRGHOZDVDSSOLHG7KLVJURXSFRQWULEXWLRQPHWKRGUHTXLUHVWKHXVHRI SDUDPHWHUVVXFKDVWKHUHODWLYHPROHFXODUYROXPHVDQGVXUIDFHDUHDVRISXUHVSHFLHVDVZHOO DVWKHLQWHUDFWLRQSDUDPHWHUVEHWZHHQWKHGLIIHUHQWJURXSVRIHDFKPROHFXOH7KHYDOXHVIRU WKHVHSDUDPHWHUVDUHSUHVHQWHGLQ7DEOHDQG7DEOH  7DEOH5HODWLYHPROHFXODUYROXPHDQGVXUIDFHDUHDRISXUHVSHFLHV81,)$&SDUDPHWHUV   &RPSRXQG *URXS 6XEJURXS *URXS1DPH ν νν ν L  5 N  4 N  $FHWDOGHK\GH   &+  FKDLQHQGJURXS      +&2    *O\FHURO   &+  FKDLQPLGGOHJURXS      &+FKDLQPLGGOHJURXS      2+    :DWHU   +  2    *($   &+  FKDLQHQGJURXS      &+  FKDLQPLGGOHJURXS      &+FKDLQPLGGOHJURXS      2+      &+  2      &+2      7DEOH²%LQDU\LQWHUDFWLRQSDUDPHWHUVIRUWKH81,)$&JURXSVSUHVHQWHGLQ7DEOH   D PN                                      7 +(502'<1$0,&$1' . ,1(7,& 6 78'<2) *($  6 <17+(6,67+528*+$1 $ &(7$/,=$7,21 5 ($&7,21     ,W VKRXOG EH QRWLFHG WKDW IRU WKLV SDUWLFXODU V\VWHP D VLPSOLILFDWLRQ ZDV DVVXPHG DFFRUGLQJZKLFKWKHJURXSSDUWLWLRQIRUDOO*($LVRPHUVZDVWKHVDPHDOORZLQJWRKDQGOHWKH LVRPHULF PL[WXUH DV D VLQJOH FRPSRXQG $OWKRXJK WKLV VLPSOLILFDWLRQ PLJKW LQWURGXFH VRPH HUURUVLQWKHHQVXLQJFDOFXODWLRQVLWVPDJQLWXGHVKRXOGEHQHJOLJLEOHVLQFHRQHLVGHDOLQJZLWK DQLVRPHULFPL[WXUHDQGLWVFRPSRQHQWVDUHH[SHFWHGWRSUHVHQWVLPLODUSURSHUWLHV 7KH FKHPLFDO HTXLOLEULXP FRQVWDQW FDQ DOVR EH H[SUHVVHG DV D IXQFWLRQ RI WKH UHDFWLRQ VWDQGDUG*LEEVIUHHHQHUJ\  * ∆ DQGWHPSHUDWXUH . DFFRUGLQJWRHTXDWLRQ  0 exp ν § · ∆ = − = ¨ ¸ © ¹ ∏ i eq i i G K a RT    ZKHUH 5 LVWKHLGHDOJDVFRQVWDQW)XUWKHUPRUHHTXDWLRQGHVFULEHVWKHUHODWLRQVKLS EHWZHHQ WKH UHDFWLRQ VWDQGDUG *LEEV IUHH HQHUJ\ ZLWK WKH UHDFWLRQ VWDQGDUG HQWKDOS\ DQG HQWURS\  + ∆ DQG  6 ∆ UHVSHFWLYHO\  0 0 0 G H T S ∆ = ∆ − ∆    :LWK WKH SXUSRVH RI HYDOXDWLQJ WKH FKHPLFDO HTXLOLEULXP FRQVWDQW IRU WKH V\QWKHVLV RI *($VHYHUDOH[SHULPHQWVZHUHSHUIRUPHGUHDFWLQJJO\FHURODQGDFHWDOGHK\GHZLWKGLIIHUHQW LQLWLDO PRODU UDWLRV DW YDULRXV WHPSHUDWXUHV DQG WKH UHDFWLRQ HTXLOLEULXP FRPSRVLWLRQ RI HDFKFRPSRXQGZDVPHDVXUHG7KHUHVXOWVDUHVKRZQLQ7DEOH  7DEOH²(TXLOLEULXPH[SHULPHQWVFRQGLWLRQVDQGUHVXOWV  3 EDU = DQG   ZW RI $PEHUO\VWZHWXVHGLQDOOH[SHULPHQWV U $FHW*O\ 7. /LPLWLQJ5HDFWDQW &RQYHUVLRQ L L L [ ν νν ν ∏ ∏∏ ∏  L L L ν νν ν γ γγ γ ∏ ∏∏ ∏ . HT                                                                    * /<&(52/$&(7$/6352'8&7,21%< 6 ,08/$7(' 0 29,1* % (' 5 ($&725      )LJXUH     ²  (IIHFWRIWKHVWLUULQJVSHHGLQWKHUHDFWLRQUDWHDVDPHDVXUHPHQWRIH[WHUQDO PDVVWUDQVIHUOLPLWDWLRQV  7 . =   3 EDU = LQLWLDODFHWDOGHK\GHJO\FHUROPRODU UDWLR  ZW RIXQVLHYHG$PEHUO\VWVWLUULQJVSHHGRI USP   )LJXUHVKRZVQRGLIIHUHQFHVEHWZHHQWKHNLQHWLFVRIWKHUHDFWLRQVSHUIRUPHGDW USP  DQG  USP  7KLV LQGLFDWHV WKDW IRU VWLUULQJ VSHHGV DERYH  USP  WKH H[WHUQDO UHVLVWDQFHVWRPDVVWUDQVIHUVKRXOGEHFRPHQHJOLJLEOH,QRUGHUWRDVVXUHWKLVDQGGHFUHDVH WKH FRPSOH[LW\ RI WKH VWXGLHG V\VWHP D VWLUULQJ VSHHG RI  USP  ZDV GHILQHG IRU WKH IROORZLQJH[SHULPHQWV ([SHULPHQWV ZHUH DOVR SHUIRUPHG XVLQJ VDPSOHV RI $PEHUO\VW ZLWK DYHUDJH SDUWLFOH GLDPHWHUV RI  P µ  DQG  P µ  NHHSLQJ WKH UHPDLQLQJ YDULDEOHV FRQVWDQW 7KHVH H[SHULPHQWVZHUHSHUIRUPHGDWWKHKLJKHVWWHPSHUDWXUHLQWKHUDQJHVWXGLHG . VLQFH DW WKHVH FRQGLWLRQV WKH HIIHFW RI WKH PDVV WUDQVIHU SKHQRPHQRQ EHFRPHV PRUH VLJQLILFDQW FRPSDULQJWRNLQHWLFHIIHFWV6LPLODUO\WRSUHYLRXVO\UHSRUWHGVWXGLHVUHJDUGLQJDFHWDOL]DWLRQ UHDFWLRQVFDWDO\VHGE\WKHLRQH[FKDQJHUHVLQ$PEHUO\VW  WKHVHH[SHULPHQWVDOORZHGWR FRQFOXGHWKDWWKLVUHDFWLRQWDNHVSODFHLQWKHSUHVHQFHRILQWHUQDOPDVVWUDQVIHUOLPLWDWLRQV ,QVHFWLRQDPRUHGHWDLOHGGLVFXVVLRQRYHUWKLVWRSLFZLOOEHFRQGXFWHG   Ϭй ϮϬй ϰϬй ϲϬй ϴϬй ϭϬϬй Ϭ ϭϬϬ ϮϬϬ ϯϬϬ ϰϬϬ ϱϬϬ ϲϬϬ ŽŶǀĞƌƐŝŽŶ dŝŵĞ;ŵŝŶͿ ϰϱϬƌƉŵ ϯϬϬƌƉŵ ϮϱϬƌƉŵ 7 +(502'<1$0,&$1' . ,1(7,& 6 78'<2) *($  6 <17+(6,67+528*+$1 $ &(7$/,=$7,21 5 ($&7,21     0DWKHPDWLFDO0RGHODQG1XPHULFDO6ROXWLRQ $ PDWKHPDWLFDO PRGHO ZDV LPSOHPHQWHG FRQVLGHULQJ D EDWFK UHDFWRU RSHUDWLQJ XQGHU LVRWKHUPDOFRQGLWLRQV3UHOLPLQDU\UHVXOWVVKRZHGWKDWLIWKHVWLUULQJVSHHGZDVVHWWR USP H[WHUQDOPDVVWUDQVIHUUHVLVWDQFHVZHUHQHJOLJLEOH2QWKHRWKHUKDQGWKHSRVVLELOLW\ RI WKH H[LVWHQFH RI LQWHUQDO PDVVWUDQVIHU OLPLWDWLRQV RI WKH VSHFLHV WKURXJK WKH FDWDO\VW SDUWLFOHV SRUHV PXVW EH FRQVLGHUHG $PEHUO\VW KDV D ELGLVSHUVH SRUH VL]H GLVWULEXWLRQ FRQWDLQLQJ PLFUR DQG PDFURSRUHV   7KH UHDFWDQWV VKRXOG ILUVW GLIIXVH WKURXJK WKH PDFURSRUHVWRWKHH[WHUQDOVXUIDFHRIPLFURVSKHUHVDQGWKHQSHQHWUDWHLQWRWKHJHOSKDVH,Q WKLVZRUNGLIIXVLRQWKURXJKWKHPDFURSRUHVRIWKHSDUWLFOHVDQGUHDFWLRQDWWKHPLFURVSKHUH DFWLYH VLWHV ZHUH FRQVLGHUHG 'LIIXVLRQ LQVLGH WKH JHO PLFURVSKHUHV ZDV FRQVLGHUHG WR EH LQILQLWHO\IDVW7KLVDSSURDFKKDVEHHQFRUURERUDWHGE\VHYHUDOZRUNV   7DNLQJ LQWR DFFRXQW WKH SUHYLRXV VWDWHPHQWV WKH PDVV EDODQFHV IRU WKH EXON DQG LQWUDSDUWLFOHIOXLGFDQEHZULWWHQDFFRUGLQJWRHTXDWLRQVDQG  , , , 1 3 ε ε = ∂ ∂§ · − = − ¨ ¸ ∂ ∂ © ¹ P p i b i b eff i p b r R C CD t R r   ( ) , , 2 , 2 11 p i p i p eff i p i s C C D r t r r r ε ε ν ρ ∂ ∂ § · ∂ = + − ℜ ¨ ¸ ∂ ∂ ∂ © ¹   ,QWKHVHHTXDWLRQVWKHLQGH[ L UHIHUVWRDUHDFWLRQVSHFLHVDFHWDOGHK\GHJO\FHURO*($ RU ZDWHU  E L &  DQG  S L &  UHSUHVHQW WKH PRODU FRQFHQWUDWLRQV HYDOXDWHG LQ WKH EXON DQG LQWUDSDUWLFOH IOXLG UHVSHFWLYHO\ S 5  UHSUHVHQWV WKH FDWDO\VW SDUWLFOH UDGLXV  HII L '  LV WKH HIIHFWLYHGLIIXVLRQFRHIILFLHQW E ε DQG S ε DUHWKHEXONDQGWKHFDWDO\VWSDUWLFOHSRURVLWLHV UHVSHFWLYHO\IRUWKHVHWH[SHULPHQWVSHUIRUPHGWKHEXONSRURVLW\YDOXHUDQJHGIURPWR  ρ V LVWKHVROLGGHQVLW\ L ν LVWKHVWRLFKLRPHWULFFRHIILFLHQWDQG ℜ LVWKHUHDFWLRQ UDWHEDVHGRQWKHORFDOLQWUDSDUWLFOH FRPSRVLWLRQ7KHPHWKRGIRU FRPSXWLQJ WKHHIIHFWLYH GLIIXVLRQ FRHIILFLHQWV DQG WKH SK\VLFDO SURSHUWLHV RI WKH UHDFWLRQ VSHFLHV UHTXLUHG IRU WKDW SXUSRVHDUHGHVFULEHGLQ$SSHQGL[ )RUWKLVPRGHORQHFDQDVVXPHWKHIROORZLQJLQLWLDOFRQGLWLRQV  0 , , 0 b i b i t C C = → =   0 , , 0 p i p i t C C = → =   * /<&(52/$&(7$/6352'8&7,21%< 6 ,08/$7(' 0 29,1* % (' 5 ($&725     DQGERXQGDU\FRQGLWLRQV  , 0 0 p i C r t ∂ = → = ∂   , , = = → = p p b i p i r R r R C C   7KHUHDFWLRQUDWHZDVGHVFULEHGE\WZRGLIIHUHQWPRGHOVSVHXGRKRPRJHQHRXV3+DQG /DQJPXLUî+LQVKHOZRRGî+RXJHQî:DWVRQ /++: 7KH 3+ PRGHO FRQVLGHUV D UHYHUVLEOH UHDFWLRQRIILUVWRUGHULQHDFKVSHFLHVDQGFDQEHH[SUHVVHGLQWHUPVRIDFWLYLWLHVDVVKRZQLQ HTXDWLRQ  § · ℜ = − ¨ ¸ ¨ ¸ © ¹ GEA W c Ac Gly eq a a k a a K    ZKHUH F N UHSUHVHQWVWKHUHDFWLRQNLQHWLFFRQVWDQW 7KH/++: PRGHO KDV DOUHDG\ EHHQ XVHG WRGHVFULEH WKHUHDFWLRQ RI DFHWDOGHK\GH ZLWK VHYHUDOOLQHDUFKDLQDOFRKROVPHWKDQRO  HWKDQRO  DQGEXWDQRO  $VVWDWHGE\SUHYLRXV DXWKRUVWKLVPRGHOFRPSULVHVWKHDGVRUSWLRQRIERWKUHDFWDQWVWKHVXUIDFHUHDFWLRQEHWZHHQ WKHP WR IRUP DQ DGVRUEHG KHPLDFHWDO WKH VXUIDFH UHDFWLRQ ZLWK WKH IRUPDWLRQ RI ZDWHU FRQVLGHUHG WKH UDWHGHWHUPLQLQJ VWHS WKH VXUIDFH UHDFWLRQ ZLWK WKH IRUPDWLRQ RI WKH DFHWDODQGWKHGHVRUSWLRQRIERWKSURGXFWV$GGLWLRQDOO\$PEHUO\VWKDVGHPRQVWUDWHGD KLJKHU DGVRUSWLRQ FDSDFLW\ IRU ZDWHU WKDQ IRU WKH RWKHU UHDFWLRQ VSHFLHV 7KHUHIRUH WKH /++:PRGHOFDQEHH[SUHVVHGE\WKHVLPSOLILHGHTXDWLRQ    ( ) 2 , 1 § · − ¨ ¸ ¨ ¸ © ¹ ℜ = + GEA W Ac Gly eq c s W W a a a a K k K a    ZKHUH  V : . UHSUHVHQWVWKHZDWHUDGVRUSWLRQHTXLOLEULXPFRQVWDQW 7KHWHPSHUDWXUHGHSHQGHQFHRIWKHUHDFWLRQNLQHWLFDQGHTXLOLEULXPDGVRUSWLRQFRQVWDQWV LV H[SUHVVHG E\ WKH $UUKHQLXV HTXDWLRQ  DQG 9DQ·W +RII HTXDWLRQ  HTXDWLRQV UHVSHFWLYHO\  7 +(502'<1$0,&$1' . ,1(7,& 6 78'<2) *($  6 <17+(6,67+528*+$1 $ &(7$/,=$7,21 5 ($&7,21     0exp a c c E k k RT § · = − ¨ ¸ © ¹   0 , , , exp ∆ § · = − ¨ ¸ © ¹ s W s W s W H K K RT   7KH YDULDEOHV  F N  DQG  : V .  UHSUHVHQW WKH $UUKHQLXV DQG 9DQ·W +RII HTXDWLRQV SUH H[SRQHQWLDO IDFWRUV UHVSHFWLYHO\ ZKLOH D (  UHSUHVHQWV WKH UHDFWLRQ DFWLYDWLRQ HQHUJ\ DQG : V +∆ UHSUHVHQWVZDWHUDGVRUSWLRQHQWKDOS\ 7KHFRPPHUFLDOVRIWZDUHJ35206*HQHUDO3URFHVV0RGHOOLQJ6\VWHPYHUVLRQZDV XVHGWRVROYHWKHPRGHOHTXDWLRQVIURPHTXDWLRQWRDQGWRHVWLPDWHWKHYDOXHVRI WKHXQNQRZQSDUDPHWHUV D ( DQG  F N IRUWKH3+PRGHODQG D (   F N  : V +∆ DQG  : V . IRU WKH /++: PRGHO 7KHSDUWLDO GLIIHUHQWLDO HTXDWLRQV ZHUH WUHDWHG XVLQJ J35206 QXPHULFDO VROYHU '$62/9 GLVFUHWLVLQJ WKH UDGLDO GRPDLQ WKURXJK D FHQWUHG ILQLWHHOHPHQW PHWKRG RI VHFRQG RUGHU DQG XVLQJ  QRQXQLIRUP GLVFUHWLVDWLRQ LQWHUYDOV 7KH HVWLPDWLRQ RI WKH SDUDPHWHUV IRU WKH SURSRVHG UHDFWLRQ UDWH PRGHOV ZDV FDUULHG RXW XVLQJ WKH J35206 ´3DUDPHWHU(VWLPDWLRQµWRRO7KHH[SHULPHQWDOGDWDZHUHILWWHGE\WKHPD[LPXPOLNHOLKRRG PHWKRG,WVREMHFWLYHIXQFWLRQ Φ LVJLYHQE\  ( ) ( ) ( ) 2 exp mod 2 2 1 1 1 ln 2 min ln 2 2 j NM NE jk jk jk j k jk X X N θ π σ σ = =  ½ ª º − ° ° « » Φ = + + ® ¾ « » ° ° ¬ ¼ ¯ ¿ ¦ ¦    ZKHUH θ LVWKHVHWRISDUDPHWHUVWREHHVWLPDWHG H[S MN ; DQG PRG MN ; DUHWKH WK N PHDVXUHG DQGSUHGLFWHGYDOXHVUHVSHFWLYHO\IRUWKHFRQYHUVLRQLQH[SHULPHQW M   MN σ LVWKHYDULDQFH LQFRQYHUVLRQ 1 UHSUHVHQWVWKHWRWDOQXPEHURIPHDVXUHPHQWVGXULQJDOOH[SHULPHQWV 1(  UHSUHVHQWV WKH QXPEHU RI H[SHULPHQWV SHUIRUPHG DQG M 10  UHSUHVHQWV WKH QXPEHU RI PHDVXUHPHQWV RI FRQYHUVLRQ YDOXHV PDGH LQ H[SHULPHQW M  7KH SDUDPHWHU HVWLPDWLRQ WROHUDQFHZDVVHWWR  DQGDFRQVWDQWYDULDQFHPRGHOZDVDVVXPHG .LQHWLF3DUDPHWHUV(VWLPDWLRQ 7RGHWHUPLQHWKHXQNQRZQFRQVWDQWVRIHDFKPRGHODSDUDPHWULFVWXG\ZDVSHUIRUPHGLQ ZKLFK WKH HIIHFWV RI FKDQJHV LQ GHVLJQ YDULDEOHV VXFK DV WKH LQLWLDO UHDFWLRQ PHGLXP * /<&(52/$&(7$/6352'8&7,21%< 6 ,08/$7(' 0 29,1* % (' 5 ($&725     FRPSRVLWLRQWHPSHUDWXUHFDWDO\VWORDGLQJDQGSDUWLFOHVL]HZHUHDVVHVVHGDFFRUGLQJWRWKH H[SHULPHQWVSUHVHQWHGLQ7DEOH ([SHULPHQWV  DOORZHG D ILUVW HVWLPDWLRQ RI WKH DSSDUHQW UHDFWLRQ DFWLYDWLRQ HQHUJ\ WKURXJKWKHLQLWLDOUHDFWLRQUDWHPHWKRGDQGWKH$UUKHQLXVHTXDWLRQ$YDOXHRI  NPRO − ⋅ ZDVREWDLQHGZKLFKZDVXVHGDVDQLQLWLDOHVWLPDWHIRUWKHDFWLYDWLRQHQHUJ\RIWKHHQVXLQJ SDUDPHWHUHVWLPDWLRQV:KHQDGVRUSWLRQSDUDPHWHUVZHUHLQFOXGHGLQWKHUHDFWLRQUDWHODZ E\ WKH /++: PRGHO WKH YDOXH GHWHUPLQHG E\ *UDFࡤD HW DO   IRU WKH ZDWHU HQWKDOS\ RI DGVRUSWLRQ   NPRO − − ⋅  ZDV XVHG DV WKH LQLWLDO HVWLPDWH IRU WKLV YDULDEOH 7DEOH  VXPPDUL]HV WKH UHVXOWV REWDLQHG E\ WKH SDUDPHWHU HVWLPDWLRQ SURFHGXUH LPSOHPHQWHG IRU ERWK WKH 3+ DQG /++: UHDFWLRQ UDWH ODZV )RU HDFK WKH DEVHQFH RU SUHVHQFH RI LQWHUQDO PDVVWUDQVIHUUHVLVWDQFHVZDVDVVHVVHG  7DEOH(VWLPDWHGNLQHWLFSDUDPHWHUVIRUWKH3+DQG/++:PRGHOVDQGUHVSHFWLYH REMHFWLYHIXQFWLRQYDOXHV 3DUDPHWHU 3+ 3+Z0DVV 7UDQVI5HV /++: /++:Z0DVV  7UDQVI5HV ( )  D ( NPRO − ⋅     ( )    PLQ F FDW N PRO J − − ⋅ ⋅ [  [   [   [   ( )  V : + NPRO − ∆ ⋅       V : .   [   [   ) REM 1(      7KH LQFUHDVH REVHUYHG LQ WKH YDOXH RI WKH DFWLYDWLRQ HQHUJ\ ZKHQ D UHVLVWDQFH WR WKH GLIIXVLRQRIWKHFRPSRXQGVWKURXJKWKHFDWDO\VWSDUWLFOHVSRUHVZDVFRQVLGHUHGIRUWKH3+ DQG/++:PRGHOVLVDQLQGLFDWLRQWKDWWKLVSKHQRPHQRQPXVWEHWDNHQLQWRDFFRXQW7KLVLV DOVRHYLGHQFHGE\WKHH[SHULPHQWDOUHVXOWVWKDWZLOOEHVKRZQLQ)LJXUHDQG)LJXUH &RQVLGHULQJ WKLV IDFW DQG WKH UHVXOWV SUHVHQWHG LQ 7DEOH  IRU WKH REMHFWLYH IXQFWLRQ IRU HDFK PRGHO RQH FDQ FRQFOXGH WKDW WKH /++: PRGHO LQFOXGLQJ LQWUDSDUWLFOH PDVV WUDQVIHU OLPLWDWLRQVFDQGHVFULEHWKHH[SHULPHQWDOUHVXOWVPRUHDFFXUDWHO\WKDQWKHUHPDLQLQJPRGHOV )RUWKLVPRGHOLWZDVSRVVLEOHWRGHWHUPLQHDUHDFWLRQDFWLYDWLRQHQHUJ\RI  NPRO − ⋅DQG DZDWHUHQWKDOS\RIDGVRUSWLRQRIî  NPRO − ⋅ 7KHYDOXHHVWLPDWHGIRUWKHUHDFWLRQDFWLYDWLRQHQHUJ\LQWKLVZRUNLVHTXLYDOHQWWRWKRVH IRXQGE\RWKHUDXWKRUVIRUVHYHUDODFHWDOL]DWLRQVLQYROYLQJJO\FHUROFDWDO\VHGE\LRQH[FKDQJH UHVLQV$VSUHYLRXVO\PHQWLRQHG$JLUUHHWDOVWXGLHGWKHNLQHWLFEHKDYLRXURIWKHUHDFWLRQRI JO\FHUROZLWKIRUPDOGHK\GH  DQGDFHWDOGHK\GH  XVLQJ$PEHUO\VWDVFDWDO\VW7KHYDOXHV UHSRUWHG IRU WKH UHDFWLRQ DFWLYDWLRQ HQHUJLHV ZHUH   NPRO − ⋅ DQG   NPRO − ⋅ 7 +(502'<1$0,&$1' . ,1(7,& 6 78'<2) *($  6 <17+(6,67+528*+$1 $ &(7$/,=$7,21 5 ($&7,21     UHVSHFWLYHO\ +RZHYHU LQ FRPSDULVRQ ZLWK WKH SUHVHQW ZRUN WKH DXWKRUV FRQVLGHUHG D GLIIHUHQWNLQHWLFPRGHOWKH3+PRGHODQGDVVXPHGWKDWLQWHUQDODQGH[WHUQDOPDVVWUDQVIHU OLPLWDWLRQVZHUHQHJOLJLEOH,QDSXEOLFDWLRQIURP1DQGDHWDO  DVWXG\RIWKHNLQHWLFVRIWKH UHDFWLRQEHWZHHQJO\FHURODQGDFHWRQHFDWDO\VHGE\$PEHUO\VWLVFDUULHGRXW7KHDXWKRUV XVHDUDWHODZEDVHGRQWKH/++:PRGHODVLQWKHFXUUHQWZRUNEXWDVVXPHWKHDEVHQFHRI DQ\ UHVLVWDQFHV WR PDVV WUDQVIHU $ YDOXH RI   NPRO − ⋅ ZDV HVWLPDWHG IRU WKH UHDFWLRQ DFWLYDWLRQHQHUJ\)RUWKHUHDFWLRQRIEXW\UDOGHK\GHZLWKJO\FHUROFDWDO\VHGE\$PEHUO\VW UHSRUWHG E\ *XHPH] HW DO   DQ DSSDUHQW UHDFWLRQ DFWLYDWLRQ HQHUJ\ RI   NPRO − ⋅ ZDV SUHGLFWHGXVLQJD3+PRGHO 0RUHRYHUWKHUHVXOWVREWDLQHGIRUWKHV\QWKHVLVRI*($WKURXJKDQDFHWDOL]DWLRQUHDFWLRQ FDQEHFRPSDUHGZLWKWKHUHVXOWVREWDLQHGE\;L+RQJHW DO  E\WKHWUDQVDFHWDOL]DWLRQRI '((ZLWKJO\FHURO$VOLJKWO\KLJKHUDFWLYDWLRQHQHUJ\RI  NPRO − ⋅ZDVREWDLQHGIRUWKH WUDQVDFHWDOL]DWLRQ UHDFWLRQ GHVFULEHG E\ D VHFRQG RUGHU NLQHWLF PRGHO FRQVLGHULQJ WKH SUHVHQFHRILQWUDSDUWLFOHPDVVWUDQVIHUUHVLVWDQFHV $PRUHGHWDLOHGGLVFXVVLRQRYHUWKHVXLWDELOLW\RIWKH/++:NLQHWLFPRGHOLQSUHGLFWLRQ RIWKHEHKDYLRXURIWKHSUHVHQWDFHWDOL]DWLRQUHDFWLRQLVSHUIRUPHGLQWKHIROORZLQJVHFWLRQV WKURXJKWKHDQDO\VLVRIWKHH[SHULPHQWDOUHVXOWVREWDLQHGLQWKHSDUDPHWULFVWXG\FDUULHGRXW (IIHFWRI&DWDO\VW/RDGLQJ 7KHLQFUHDVHRIWKHFDWDO\VWORDGLQJIURP  ZW WR  ZW PDVVRIFDWDO\VWRYHUWKH WRWDOPDVVRIUHDFWDQWVZDVH[SHULPHQWDOO\WHVWHGDQGOHGWRDQH[SHFWHGLQFUHDVHLQWKH LQLWLDOUHDFWLRQUDWHRIDSSUR[LPDWHO\DVLWFDQEHREVHUYHGIURP)LJXUH7KLVIDFWLV GXHWRWKHLQFUHDVHLQWKHQXPEHURIDYDLODEOHDFLGFDWDO\WLFVLWHVWKDWZLOOUHVXOWLQDKLJKHU UHDFWLRQUDWH * /<&(52/$&(7$/6352'8&7,21%< 6 ,08/$7(' 0 29,1* % (' 5 ($&725      )LJXUH       (IIHFWRIWKHFDWDO\VWDPRXQWRQWKHUHDFWLRQUDWH  7 . =   3 EDU =   LQLWLDODFHWDOGHK\GHJO\FHUROPRODUUDWLRXQVLHYHG$PEHUO\VWVWLUULQJVSHHGRI USP   7KHPRGHOFRUUHFWO\GHVFULEHVWKHHIIHFWRIWKHLQFUHDVHDQGGHFUHDVHRIFDWDO\VWORDGLQJ (IIHFWRI7HPSHUDWXUH ([SHULPHQWVZHUHSHUIRUPHGDWWHPSHUDWXUHVUDQJLQJIURP . WR . WRDVVHVVWKH HIIHFW RI WKLV YDULDEOH RQ WKH UHDFWLRQ UDWH 2QFH DJDLQ WKH H[SHULPHQWDO UHVXOWV DQG WKH PRGHOSUHVHQWHGWKHVDPHEHKDYLRXU7KHFRQYHUVLRQYHUVXVWLPHSORWSUHVHQWHGLQ)LJXUH VKRZVWKDWDVWKHWHPSHUDWXUHLQFUHDVHGWKHUHDFWLRQEHFDPHIDVWHUDVH[SHFWHGE\WKH $UUKHQLXVHTXDWLRQ+RZHYHUWKHHTXLOLEULXPFRQYHUVLRQGHFUHDVHGIRUKLJKHUWHPSHUDWXUH YDOXHVDVDFRQVHTXHQFHRIWKHH[RWKHUPLFFKDUDFWHURIWKHDFHWDOL]DWLRQRIJO\FHURO  Ϭй ϮϬй ϰϬй ϲϬй ϴϬй ϭϬϬй Ϭ ϭϬϬ ϮϬϬ ϯϬϬ ϰϬϬ ϱϬϬ ŽŶǀĞƌƐŝŽŶ dŝŵĞ;ŵŝŶͿ ϬϰǁƚйĂƚĂůLJƐƚ;džƉͿ ϬϰǁƚйĂƚĂůLJƐƚ;DŽĚĞůͿ ϬϮǁƚйĂƚĂůLJƐƚ;džƉͿ ϬϮǁƚйĂƚĂůLJƐƚ;DŽĚĞůͿ 7 +(502'<1$0,&$1' . ,1(7,& 6 78'<2) *($  6 <17+(6,67+528*+$1 $ &(7$/,=$7,21 5 ($&7,21      )LJXUH       (IIHFWRIWHPSHUDWXUHRQWKHUHDFWLRQUDWH  3 EDU = LQLWLDO DFHWDOGHK\GHJO\FHUROPRODUUDWLRXQVLHYHG$PEHUO\VWVWLUULQJVSHHGRI USP   (IIHFWRIWKH,QLWLDO&RPSRVLWLRQRIWKH5HDFWLRQ0HGLXP 7KH FRQYHUVLRQ DV D IXQFWLRQ RI WLPH IRU DQ HTXLPRODU PL[WXUH RI JO\FHURO DQG DFHWDOGHK\GHZDVFRPSDUHGZLWKWKHFRQYHUVLRQIRUDPL[WXUHZLWKDQDFHWDOGHK\GHJO\FHURO PRODUUDWLRRIWRDQDO\VHWKHHIIHFWRIWKHLQLWLDOPRODUUDWLRRIWKHUHDFWDQWV)LJXUH   Ϭй ϮϬй ϰϬй ϲϬй ϴϬй ϭϬϬй Ϭ ϱϬ ϭϬϬ ϭϱϬ ϮϬϬ ŽŶǀĞƌƐŝŽŶ dŝŵĞ;ŵŝŶͿ dсϯϱϴ<ϬϰǁƚйĂƚ;džƉͿ dсϯϱϴ<ϬϰǁƚйĂƚ;DŽĚĞůͿ dсϯϱϯ<ϬϰǁƚйĂƚ;džƉͿ dсϯϱϯ<ϬϰǁƚйĂƚ;DŽĚĞůͿ dсϯϯϯ<ϬϰǁƚйĂƚ;džƉͿ dсϯϯϯ<ϬϰǁƚйĂƚ;DŽĚĞůͿ dсϯϱϯ<ϬϮǁƚйĂƚ;džƉͿ dсϯϱϯ<ϬϮǁƚйĂƚ;DŽĚĞůͿ dсϯϯϯ<ϬϮǁƚйĂƚ;džƉͿ dсϯϯϯ<ϬϮǁƚйĂƚ;DŽĚĞůͿ dсϯϭϯ<ϬϮǁƚйĂƚ;džƉͿ dсϯϭϯ<ϬϮǁƚйĂƚ;DŽĚĞůͿ * /<&(52/$&(7$/6352'8&7,21%< 6 ,08/$7(' 0 29,1* % (' 5 ($&725      )LJXUH       (IIHFWRIWKHLQLWLDOUHDFWDQWPRODUUDWLRRQWKHUHDFWLRQUDWH  7 . =   3 EDU =   ZW  RIXQVLHYHG$PEHUO\VWVWLUULQJVSHHGRI USP   )URPWKH UHVXOWVVKRZQLQ)LJXUHLWFDQEHREVHUYHGWKDWWKHUHDFWLRQSURFHHGHG IDVWHU ZKHQ RQH RI WKH UHDFWDQWV ZDV XVHG LQ H[FHVV DV FRXOG EH SUHGLFWHG E\ WKH LPSOHPHQWHGPRGHO 7KHHIIHFWRIWKHSUHVHQFHRIWKHSURGXFWVLQWKHLQLWLDOUHDFWLRQPL[WXUHZDVDOVRWHVWHG )LJXUH  Ϭй ϮϬй ϰϬй ϲϬй ϴϬй ϭϬϬй Ϭ ϭϬϬ ϮϬϬ ϯϬϬ ϰϬϬ ϱϬϬ ŽŶǀĞƌƐŝŽŶ dŝŵĞ;ŵŝŶͿ ϭϮϱĐĞƚ'ůLJZĂƚŝŽ;džƉͿ ϭϮϱĐĞƚ'ůLJZĂƚŝŽ;DŽĚĞůͿ ϭϬĐĞƚ'ůLJZĂƚŝŽ;džƉͿ ϭϬĐĞƚ'ůLJZĂƚŝŽ;DŽĚĞůͿ 7 +(502'<1$0,&$1' . ,1(7,& 6 78'<2) *($  6 <17+(6,67+528*+$1 $ &(7$/,=$7,21 5 ($&7,21      )LJXUH       (IIHFWRQWKHUHDFWLRQUDWHRIWKHSUHVHQFHRISURGXFWVLQWKHLQLWLDOPL[WXUH   3 EDU = LQLWLDODFHWDOGHK\GHJO\FHUROPRODUUDWLR  ZW  RIXQVLHYHG$PEHUO\VW VWLUULQJVSHHGRI USP   $V H[SHFWHG WKH LQLWLDO UHDFWLRQ UDWH ZDV ORZHU ZKHQ *($ DQG ZDWHU ZHUH LQWURGXFHG LQWR WKH LQLWLDO PL[WXUH 7KHVH UHVXOWV DUH UHODWHG WR WKH FKDQJH LQ WKH ´GULYLQJ IRUFHµ WR UHDFKHTXLOLEULXPSURPRWHGE\WKHGLIIHUHQWLQLWLDOFRPSRVLWLRQVRIWKHUHDFWLRQPHGLXP7KH PRGHOGRHVQRWILWWKLVEHKDYLRXUDVDFFXUDWHO\DVIRUWKHRWKHUH[SHULPHQWV7KHUHDFWLRQ UDWHSUHGLFWHGE\WKHPRGHOZDVVOLJKWO\KLJKHUWKDQWKHH[SHULPHQWDOYDOXH+RZHYHUWKH UHVXOWVDUHVWLOOVDWLVIDFWRU\ (YDOXDWLRQRI0DVV7UDQVIHU/LPLWDWLRQV ,QVHFWLRQLWZDVSRVVLEOHWRFRQILUPWKDWLIWKHVWLUULQJVSHHGZDVVHWWR USP  WKHH[WHUQDOUHVLVWDQFHWRPDVVWUDQVIHUFRXOGEHUHGXFHGXQWLOLWEHFRPHVLUUHOHYDQW )XUWKHUPRUHVLQFH$PEHUO\VWDFLGVLWHFRQFHQWUDWLRQZDVUHSRUWHGWREHLQGHSHQGHQW RILWVSDUWLFOHVL]H  WKHDVVHVVPHQWRIWKHH[LVWHQFHRILQWUDSDUWLFOHPDVVWUDQVIHUOLPLWDWLRQV ZDV EDVHG RQ WKH UHDFWLRQ NLQHWLF EHKDYLRXU ZKHQ FDWDO\VHG E\ SDUWLFOHV ZLWK DYHUDJH GLDPHWHUVRI P µ DQG P µ DVVKRZQLQ)LJXUH  Ϭй ϮϬй ϰϬй ϲϬй ϴϬй ϭϬϬй Ϭ ϭϬϬ ϮϬϬ ϯϬϬ ϰϬϬ ϱϬϬ ŽŶǀĞƌƐŝŽŶ dŝŵĞ;ŵŝŶͿ dсϯϰϯ<dž;tͿсdž;'Ϳсϳй;džƉͿ dсϯϰϯ<dž;tͿсdž;'Ϳсϳй;DŽĚĞůͿ dсϯϮϯ<dž;tͿсdž;'Ϳсϭϱй;džƉͿ dсϯϮϯ<dž;tͿсdž;'Ϳсϭϱй;DŽĚĞůͿ * /<&(52/$&(7$/6352'8&7,21%< 6 ,08/$7(' 0 29,1* % (' 5 ($&725      'D6LOYD&;$9/&*RQDOYHVDQG&-$0RWD:DWHUWROHUDQW]HROLWHFDWDO\VW IRUWKHDFHWDOLVDWLRQRIJO\FHURO*UHHQ&KHPLVWU\S  6LOYD 3+5 9/& *RQoDOYHV DQG &-$ 0RWD *O\FHURO DFHWDOV DV DQWLIUHH]LQJ DGGLWLYHVIRUELRGLHVHO%LRUHVRXUFH7HFKQRORJ\S  'HXWVFK - $ 0DUWLQ DQG + /LHVNH ,QYHVWLJDWLRQV RQ KHWHURJHQHRXVO\ FDWDO\VHG FRQGHQVDWLRQVRIJO\FHUROWRF\FOLFDFHWDOV-RXUQDORI&DWDO\VLVS   %DOOLQL 5 * %RVLFD % )UXOODQWL 5 0DJJL * 6DUWRUL DQG ) 6FKURHU  'LR[RODQHV IURP FDUERQ\O FRPSRXQGV RYHU ]HROLWH +6= DV D UHXVDEOH KHWHURJHQHRXVFDWDO\VW7HWUDKHGURQ/HWWHUVS  8PEDUNDU6%79.RWEDJL$9%LUDGDU53DVULFKD-&KDQDOH0.'RQJDUH $60DPHGH&/DQFHORWDQG(3D\HQ$FHWDOL]DWLRQRIJO\FHUROXVLQJPHVRSRURXV 0R2VXE!VXE!6L2VXE!VXE! VROLG DFLG FDWDO\VW -RXUQDO RI 0ROHFXODU &DWDO\VLV$&KHPLFDOS  7DQDND < 1 6DZDPXUD DQG 0 ,ZDPRWR +LJKO\ HIIHFWLYH DFHWDOL]DWLRQ RI DOGHK\GHVDQGNHWRQHVZLWKPHWKDQRORQVLOLFHRXVPHVRSRURXVPDWHULDO7HWUDKHGURQ /HWWHUVS  'DL < %' /L +' 4XDQ DQG &; / >+PLP@3:2 $ KLJKHIILFLHQW DQG JUHHQ FDWDO\VW IRU WKH DFHWDOL]DWLRQ RI FDUERQ\O FRPSRXQGV &KLQHVH &KHPLFDO /HWWHUVS  $JLUUH , , *DUFtD - 5HTXLHV 9/ %DUULR 0% *HPH] -) &DPEUD DQG 3/ $ULDV *O\FHURO DFHWDOV NLQHWLF VWXG\ RI WKH UHDFWLRQ EHWZHHQ JO\FHURO DQG IRUPDOGHK\GH%LRPDVVDQG%LRHQHUJ\S  *HPH] 0% - 5HTXLHV , $JLUUH 3/ $ULDV 9/ %DUULR DQG -) &DPEUD $FHWDOL]DWLRQ UHDFWLRQ EHWZHHQ JO\FHURO DQG QEXW\UDOGHK\GH XVLQJ DQ DFLGLF LRQ H[FKDQJH UHVLQ .LQHWLF PRGHOOLQJ &KHPLFDO (QJLQHHULQJ -RXUQDO   S   1DQGD 05 = <XDQ : 4LQ +6 *KD]LDVNDU 0$ 3RLULHU DQG && ;X 7KHUPRG\QDPLF DQG NLQHWLF VWXGLHV RI D FDWDO\WLF SURFHVV WR FRQYHUW JO\FHURO LQWR VRONHWDODVDQR[\JHQDWHGIXHODGGLWLYH)XHO3DUW$S  3ROLQJ%(-03UDXVQLW]DQG-32&RQQHOO3URSHUWLHVRI*DVHVDQG/LTXLGVWK (GLWLRQ0F*UDZ+LOO  6LOYD 9070 DQG $( 5RGULJXHV .LQHWLF VWXGLHV LQ D EDWFK UHDFWRU XVLQJ LRQ H[FKDQJH UHVLQ FDWDO\VWV IRU R[\JHQDWHV SURGXFWLRQ 5ROH RI PDVV WUDQVIHU PHFKDQLVPV&KHPLFDO(QJLQHHULQJ6FLHQFHS  *UDoD16/63DLV90706LOYDDQG$(5RGULJXHV2[\JHQDWHGELRIXHOVIURP EXWDQRO IRU GLHVHO EOHQGV 6\QWKHVLV RI WKH DFHWDO GLEXWR[\HWKDQH FDWDO\]HG E\ DPEHUO\VW LRQH[FKDQJH UHVLQ ,QGXVWULDO DQG (QJLQHHULQJ &KHPLVWU\ 5HVHDUFK S  4XLQWD )HUUHLUD 50 &$ $OPHLGD&RVWD DQG $( 5RGULJXHV +HWHURJHQHRXV 0RGHOV RI 7XEXODU 5HDFWRUV 3DFNHG ZLWK ,RQ([FKDQJH 5HVLQV࣯ 6LPXODWLRQ RI WKH 07%(6\QWKHVLV,QGXVWULDO(QJLQHHULQJ&KHPLVWU\5HVHDUFKS   ,KP6.-+$KQDQG<'-R,QWHUDFWLRQRI5HDFWLRQDQG0DVV7UDQVIHULQ,RQ ([FKDQJH5HVLQ&DWDO\VWV,QGXVWULDO(QJLQHHULQJ&KHPLVWU\5HVHDUFK S  'RJX7($\GLQ1%R].0XUWH]DRJOXDQG*'RJX'LIIXVLRQ5HVLVWDQFHVDQG &RQWULEXWLRQRI6XUIDFH'LIIXVLRQLQ7$0(DQG7$((3URGXFWLRQ8VLQJ$PEHUO\VW ,QWHUQDWLRQDO-RXUQDORI&KHPLFDO5HDFWRU(QJLQHHULQJ  6XQGPDFKHU.56=KDQJDQG8+RIIPDQQ0DVVWUDQVIHUHIIHFWVRQNLQHWLFVRI QRQLGHDO OLTXLG SKDVH HWK\O WHUWEXW\O HWKHU IRUPDWLRQ &KHPLFDO (QJLQHHULQJ  7HFKQRORJ\S  *DQGL *. 9070 6LOYD DQG $( 5RGULJXHV 3URFHVV GHYHORSPHQW IRU GLPHWK\ODFHWDO V\QWKHVLV 7KHUPRG\QDPLFV DQG UHDFWLRQ NLQHWLFV ,QGXVWULDO DQG (QJLQHHULQJ&KHPLVWU\5HVHDUFKS  6LOYD9070 DQG $( 5RGULJXHV 6\QWKHVLVRI GLHWK\ODFHWDOWKHUPRG\QDPLFDQG NLQHWLFVWXGLHV&KHPLFDO(QJLQHHULQJ6FLHQFHS 7 +(502'<1$0,&$1' . ,1(7,& 6 78'<2) *($  6 <17+(6,67+528*+$1 $ &(7$/,=$7,21 5 ($&7,21      )LJXHLUHGR -/ DQG )5 5LEHLUR &DWiOLVH KHWHURJpQHD  QG  HG  )XQGDomR &DORXVWH*XOEHQNLDQ  ;X =3 DQG .7 &KXDQJ (IIHFW RI LQWHUQDO GLIIXVLRQ RQ KHWHURJHQHRXV FDWDO\WLF HVWHULILFDWLRQ RI DFHWLF DFLG &KHPLFDO (QJLQHHULQJ 6FLHQFH   S    /HYHQVSLHO2&KHPLFDO5HDFWLRQ(QJLQHHULQJUG(GLWLRQ-RKQ:LOH\6RQV  3|SNHQ7/*|W]HDQG-*PHKOLQJ5HDFWLRQNLQHWLFVDQGFKHPLFDOHTXLOLEULXPRI KRPRJHQHRXVO\ DQG KHWHURJHQHRXVO\ FDWDO\]HG DFHWLF DFLG HVWHULILFDWLRQ ZLWK PHWKDQRO DQG PHWK\O DFHWDWH K\GURO\VLV ,QGXVWULDO DQG (QJLQHHULQJ &KHPLVWU\ 5HVHDUFKS       &KDSWHU 6HOHFWLRQRID6ROYHQWIRUDQ ,QWHJUDWHG5HDFWLYH²$GVRUSWLYH3URFHVV IRUWKH6\QWKHVLVRI*($  $'$37(' )520 )DULD 539 3HUHLUD &60 6LOYD 9070 /RXUHLUR -0 5RGULJXHV $( *O\FHURO YDORULVDWLRQ DV ELRIXHOV 6HOHFWLRQ RI D VXLWDEOH VROYHQW IRU DQ LQQRYDWLYHSURFHVVIRUWKHV\QWKHVLVRI*($&KHPLFDO(QJLQHHULQJ-RXUQDOS     ,QWURGXFWLRQ 7KH UHVHDUFK XQGHUWDNHQ LQ WKH SUHYLRXV FKDSWHU KDV FRQWULEXWHG WR D GHHSHU XQGHUVWDQGLQJRIWKHSKHQRPHQDXQGHUO\LQJWKHDFHWDOL]DWLRQUHDFWLRQEHWZHHQJO\FHURODQG DFHWDOGHK\GHXVLQJ$PEHUO\VWLRQH[FKDQJHUHVLQDVDFLGFDWDO\VW7KHDGYDQWDJHVRIWKLV UHDFWLRQURXWHRYHUDOWHUQDWLYHURXWHVIRUWKHV\QWKHVLVRI*O\FHURO(WK\O$FHWDO*($KDYH DOUHDG\EHHQH[SRVHG7KHIRUPDWLRQRIZDWHUDVDVHFRQGDU\SURGXFWUHSUHVHQWVWKHPDMRU GUDZEDFNRIWKLVUHDFWLRQ$V*($LVLQWHQGHGWREHDSSOLHGDVDIXHODGGLWLYHZDWHUPXVW RQO\EHSUHVHQWLQUHVLGXDODPRXQWVLQWKHILQDOSURGXFW&RQVHTXHQWO\WKHDVVD\UHTXLUHGIRU *($PLJKWLPSO\VLJQLILFDQWVHSDUDWLRQFRVWV,QWKLVVFHQDULRWKHXVHRIDPXOWLIXQFWLRQDO UHDFWRU LQWHJUDWLQJ UHDFWLRQ DQG VHSDUDWLRQ SURFHVVHV LQ D VLQJOH XQLW FRXOG UHSUHVHQW DQ HIILFLHQWVROXWLRQ 6 (/(&7,212)$ 6 2/9(17)25$1 , 17(*5$7(' 5 ($&7,9( ²$ '62537,9( 3 52&(66)257+( 6 <17+(6,62) *($    0XOWLIXQFWLRQDO UHDFWRUV SULQFLSOHV IDOO XQGHU WKH IUDPHZRUN RI WKH VWDWH RI WKH DUW RI SURFHVVLQWHQVLILFDWLRQVWUDWHJLHV7KURXJKWKHFRQWLQXRXVUHPRYDORIWKHSURGXFWVIURPWKH UHDFWLRQPHGLDWKHVHXQLWVSURPRWHWKHWKHUPRG\QDPLFHTXLOLEULXPGLVSODFHPHQWIDYRXULQJ SURGXFWV IRUPDWLRQ DQGLQFUHDVLQJ WKH UHDFWLRQ H[WHQW 7KHVH K\EULG XQLWV DUH DOVR DEOHWR LPSURYH WKH VHOHFWLYLW\ WRZDUGV D SURGXFW DQG KDYH WKH SRWHQWLDO WR UHGXFH FDSLWDO LQYHVWPHQW DQG HQHUJ\ FRQVXPSWLRQ )RU WKHVH UHDVRQV PXOWLIXQFWLRQDO UHDFWRUV DUH FRQVLGHUHG DV D VXVWDLQDEOH DSSURDFK WR WKH HQYLURQPHQWDO DQG HFRQRPLF FKDOOHQJHV RI SURFHVVHQJLQHHULQJ   7KHLPSOHPHQWDWLRQRIPXOWLIXQFWLRQDOUHDFWRUV IRU DFHWDOV\QWKHVLVKDVSUHVHQWHGYHU\ VDWLVIDFWRU\ UHVXOWV   7KH SURGXFWLRQ RI GLPHWKR[\HWKDQH   '0( GLHWKR[\HWKDQH   '(( DQG GLEXWKR[\HWKDQH   '%( ZDV DFKLHYHG E\ WKH GLUHFW DFHWDOL]DWLRQ RI DFHWDOGHK\GHZLWKPHWKDQROHWKDQRODQGEXWDQROUHVSHFWLYHO\LQD6LPXODWHG0RYLQJ%HG 5HDFWRU60%57KLVXQLWFRQVWLWXWHGE\DVHULHVRILQWHUFRQQHFWHGFKURPDWRJUDSKLFFROXPQV SDFNHGZLWK$PEHUO\VWZKLFKFDQDFWERWKDVFDWDO\VWDQGDGVRUEHQWZDVDEOHWRVKLIW WKHUHDFWLRQWKHUPRG\QDPLFHTXLOLEULXPWKURXJKWKHVHOHFWLYHDGVRUSWLRQRIZDWHUUHPRYLQJ WKLVXQGHVLUHGFRPSRXQGIURPWKHILQDOSURGXFWVWUHDP7KXVRQHFDQDVVXPHWKDWWKH60%5 PLJKW EHD VXLWDEOH WHFKQRORJ\ IRU WKH SURGXFWLRQ RI *($ IURP JO\FHURODQG DFHWDOGHK\GH 7KLVVWDWHPHQWLVFRUURERUDWHGE\WKHSDWHQWLQJRIDQLQGXVWULDOSURFHVVIRUWKHSURGXFWLRQRI F\FOLFDFHWDOVLQD60%5E\$5.(0$)UDQFH   ,QPRVW60%5DSSOLFDWLRQVUHSRUWHGLQWKHRSHQOLWHUDWXUHRQHRIWKHUHDFWDQWVZDVXVHG DVGHVRUEHQW   KRZHYHULQWKH*($V\QWKHVLVE\GLUHFWFRQGHQVDWLRQRIJO\FHUROZLWK DFHWDOGHK\GHWKLVPHWKRGRORJ\FDQQRWEHDSSOLHG*O\FHUROGXHWRLWVKLJKYLVFRVLW\ZRXOG VLJQLILFDQWO\LQFUHDVHWKHSUHVVXUHGURSLQWKHRSHUDWLRQXQLWDVZHOODVDGGDPDVVWUDQVIHU UHVLVWDQFHWRWKHV\VWHP3OXVLWVKLJKERLOLQJSRLQWZRXOGUHSUHVHQWDQLQFUHDVHLQWKHILQDO SURGXFW SXULILFDWLRQ FRVWV $FHWDOGHK\GH RQ WKH RWKHU KDQG LQ WKH SUHVHQFH RI DQ DFLG FDWDO\VWZLOOXQGHUJRROLJRPHUL]DWLRQUHDFWLRQV  WKXVLQRUGHUWRGHFUHDVHWKHSRVVLELOLW\ RIVLGHSURGXFWVIRUPDWLRQDFHWDOGHK\GHDPRXQWPXVWEHNHSWDVORZDVSRVVLEOH7KHUHIRUH DQRWKHUFRPSRXQGPXVWEHVHOHFWHGDVVROYHQWDQGSDUWLFXODUDWWHQWLRQPXVWEHDGGUHVVHGWR WKH DQDO\VLV RI SDUDPHWHUV UHODWHG WR LWV UHDFWLYLW\ DQG SK\VLFDO SURSHUWLHV ZLWK IRFXV RQ DGVRUSWLRQ $OWKRXJK VRPH V\VWHPDWLF VROYHQW VFUHHQLQJ PHWKRGRORJLHV KDYH EHHQ SXEOLVKHG QRQH ZDVVSHFLILFDOO\GHYHORSHGIRU60%5V7KH\DUHHLWKHUIRUVLPSOHUFKURPDWRJUDSKLFV\VWHPV    IRU JHQHULF RUJDQLF V\QWKHVLV SURFHVVHV   RU PDLQO\ RULHQWHG IRU WKH LGHQWLILFDWLRQ RI JUHHQVROYHQWV   ,QRUGHUWRVXSSUHVVWKLVQHFHVVLW\DILUVWDSSURDFKIRUDVLPSOHEXWH[SHGLWLRXVVROYHQW VFUHHQLQJPHWKRGRORJ\IRUUHDFWLYH²DGVRUSWLYHSURFHVVHVVXFKDVWKH60%5ZDVGHYHORSHGLQ WKLV&KDSWHU$OLVWFRPSULVLQJWKHPRVWFRPPRQVROYHQWVLQFKHPLFDOSURFHVVHVZDVFRPSLOHG DQG VHTXHQWLDOO\ UHGXFHG EDVHG RQ WKHRUHWLFDOSDUDPHWHUV UHODWHG ZLWK UHDFWLYH²DGVRUSWLYH SURFHVVHV UHTXLUHPHQWV 7KH VROYHQWV WKDW SUHVHQWHG WKH EHVW UHVXOWV RQ WKH WKHRUHWLFDO * /<&(52/$&(7$/6352'8&7,21%< 6 ,08/$7(' 0 29,1* % (' 5 ($&725     VFUHHQLQJZKHUHWKHQVXEMHFWHGWRH[SHULPHQWDOWHVWVWRDVVHVVLWVPLVFLELOLW\DGVRUSWLRQDQG UHDFWLRQ SURSHUWLHV ZLWK WKH VSHFLHV SUHVHQW LQ WKH VWXGLHG V\QWKHVLV V\VWHP DOORZLQJ WKH VHOHFWLRQRIDVXLWDEOHVROYHQWIRUWKHSURGXFWLRQRI*($LQD60%5 )LQDOO\ D NLQHWLF PRGHO ZDV SURSRVHG IRU WKH GLUHFW DFHWDOL]DWLRQ RI JO\FHURO ZLWK DFHWDOGHK\GHLQWKHSUHVHQFHRIWKHVHOHFWHGVROYHQW$SDUDPHWULFVWXG\FRPSULVLQJDZLGH UDQJHRIRSHUDWLQJFRQGLWLRQVZDVSHUIRUPHGLQRUGHUWRGHWHUPLQHWKHNLQHWLFSDUDPHWHUVIRU WKLVUHDFWLRQ7KHUHVXOWVZHUHFRPSDUHGZLWKWKRVHREWDLQHGIRUWKHVROYHQWIUHHUHDFWLRQ UHSRUWHGLQWKHSUHYLRXVFKDSWHU   ([SHULPHQWDO'HVFULSWLRQ &KHPLFDOVDQG&DWDO\VWV 7KHFKHPLFDOVXVHGLQWKHH[SHULPHQWDOWHVWVZHUHDFHWDOGHK\GH!JO\FHURO! DFHWRQLWULOH ! DQG QQGLPHWK\OIRUPDPLGH ! SXUFKDVHG IURP 6LJPD²$OGULFK DQG GLPHWK\OVXOIR[LGH!SXUFKDVHGIURP9:5,QWHUQDWLRQDO 5RKP+DDV$PEHUO\VWZHWLRQH[FKDQJHUHVLQZDVXVHGDVFDWDO\VW6LQFHZDWHULVD UHDFWLRQ SURGXFW DQG DGVRUEV VWURQJO\ RQ $PEHUO\VW WR DYRLG WKH FRQWDPLQDWLRQ RI WKH UHVLQ ZLWK DLU PRLVWXUH D SUHWUHDWPHQW SURFHGXUH ZDV LPSOHPHQWHG WR DVVXUH WKH XVH RI DQK\GURXV UHVLQ LQ DGVRUSWLRQ DQG UHDFWLRQ WHVWV +HQFH $PEHUO\VW ZDV ZDVKHG VHYHUDO WLPHV ZLWK GHLRQL]HG ZDWHU WKHQ ZDVKHG ZLWK HWKDQRO DQG GULHG DW  .  XQWLO WKH PDVV UHPDLQHGFRQVWDQWSULRUWRLWVXVH  ([SHULPHQWDO6HWXSDQG3URFHGXUH 6ROYHQW6HOHFWLRQ0HWKRGRORJ\0LVFLELOLW\7HVWV 0LVFLELOLW\ WHVWV ZHUH SHUIRUPHG E\ SUHSDULQJ VHYHUDO ELQDU\ PL[WXUHV FRQWDLQLQJ WKH VROYHQWDQGRQHRIWKHUHDFWDQWVWRZKLFKZDWHURU*($ZDVDGGHGLQORZDPRXQWVXQWLOSKDVH VSOLW RU WKH IRUPDWLRQ RI D VLQJOH SKDVH V\VWHP ZDV REVHUYHG GHSHQGLQJ RQ LI WKH LQLWLDO ELQDU\PL[WXUHSUHVHQWHGRQHRUWZRSKDVHVUHVSHFWLYHO\7KHWHVWVZHUHSHUIRUPHGLQ P/  FORVHGWHVWWXEHVNHSWDW . E\DZDWHUEDWK/$8'$/DXGD².|QLJVKRIHQ*HUPDQ\7KH VDPSOHVZHUH LQLWLDOO\VWLUUHG LQ D YRUWH[PL[HU DQG WKHQ DOORZHGWRVWDQG WR SURPRWHWKH SKDVHVHSDUDWLRQ 6 (/(&7,212)$ 6 2/9(17)25$1 , 17(*5$7(' 5 ($&7,9( ²$ '62537,9( 3 52&(66)257+( 6 <17+(6,62) *($     6ROYHQW6HOHFWLRQ0HWKRGRORJ\$GVRUSWLRQ7HVWV $PEHUO\VW ZHW DGVRUSWLRQ FDSDFLW\ WRZDUGV ZDWHU *($ DQG WKH VROYHQWV ZDV HVWLPDWHG WKURXJK VZHOOLQJ H[SHULPHQWV SHUIRUPHG LQ  P/  JUDGXDWHG F\OLQGHUV ZKHUH D NQRZQDPRXQWRIVRUEHQWDSSUR[LPDWHO\ J ZDVSXWLQFRQWDFWZLWK P/ RIVRUEDWHDWD FRQVWDQWWHPSHUDWXUHRI . WHPSHUDWXUHZDVNHSWWKLVORZLQRUGHUWRDYRLGHYDSRUDWLRQ IRUDSHULRGRI K 7KHILQDOVRUEHQWYROXPHZDVUHJLVWHUHG7KHVRUEHQWZDVILOWHUHGDQG ZHLJKWHG DQG LWV DGVRUSWLRQ FDSDFLW\ IRU D JLYHQ FRPSRXQG ZDV FRQVLGHUHG WR EH DQ DSSUR[LPDWLRQRILWVPDVVGLIIHUHQFHEHWZHHQWKHEHJLQQLQJDQGWKHHQGRIWKHH[SHULPHQWV 7KHSURFHGXUHZDVSHUIRUPHGDWOHDVWWKUHHWLPHVIRUHDFKFRPSRXQG  6ROYHQW6HOHFWLRQ0HWKRGRORJ\5HDFWLRQ7HVWV %DWFK UHDFWLRQV ZHUH FDUULHG RXW LQ D  P/  VWDLQOHVV VWHHO YHVVHO HTXLSSHG ZLWK D VDPSOLQJYDOYHDQGWHPSHUDWXUHDQGSUHVVXUHVHQVRUVRSHUDWLQJDW . DQG EDU )LJXUH $PDJQHWLFKRWSODWHVWLUUHUZLWKH[WHUQDOWHPSHUDWXUHFRQWUROZDVXVHGWRVXSSO\KHDW DQGWRVWLUWKHUHDFWLRQPL[WXUHVFRPSRVHGE\ PPRO RIDFHWDOGHK\GHDQGJO\FHUROGLOXWHG LQ  RI VROYHQW PRODU EDVLV $PEHUO\VW ZHW   ZW  ZDV XVHG DV FDWDO\VW 7KH H[SHULPHQWVZHUHFDUULHGRXWIRU K 6DPSOHVZHUHFROOHFWHGDWSUHGHILQHGWLPHLQWHUYDOV DQGDQDO\VHGE\JDVFKURPDWRJUDSK\DVGHVFULEHGLQVHFWLRQ  5HDFWLRQ.LQHWLFVLQWKH3UHVHQFHRIWKH6HOHFWHG6ROYHQW 7KHGHWHUPLQDWLRQRI WKH NLQHWLFV RI WKHDFHWDOL]DWLRQ RI JO\FHURO ZLWK DFHWDOGHK\GH LQ WKH SUHVHQFH RI WKH VHOHFWHG VROYHQW ZDV FDUULHG RXW LQ D FORVHG JODVVMDFNHWHG  /  YHVVHO %üFKL/DERUDWRU\(TXLSPHQW)ODZLO6ZLW]HUODQGPHFKDQLFDOO\VWLUUHGDQGHTXLSSHGZLWKD EORZRIIYDOYHSUHVVXUHDQGWHPSHUDWXUHVHQVRUV)LJXUH7KHUHDFWRUZDVRSHUDWHGLQ EDWFK PRGH DQG LWV WHPSHUDWXUH ZDV FRQWUROOHG WKURXJK D ZDWHU EDWK /$8'$ /DXGD² .|QLJVKRIHQ*HUPDQ\ 7KH NLQHWLF VWXG\ ZDV SHUIRUPHG HYDOXDWLQJ WKH HIIHFW RI SDUDPHWHUV VXFK DV VWLUULQJ VSHHGUSPDQGUSPWHPSHUDWXUH .  . DQG . LQLWLDODFHWDOGHK\GHWR JO\FHURO PRODU UDWLR   DQG  VROYHQW PRODU IUDFWLRQ   DQG  DQG FDWDO\VWORDGLQJ  ZW DQG  ZW RIWKHWRWDOUHDFWLRQPHGLXPPDVVDFFRUGLQJWRWKH H[SHULPHQWVGHVFULEHGLQ7DEOH7KHSUHVVXUHZDVVHWWR EDU ZLWKKHOLXPIRUDOOWKH H[SHULPHQWV9DSRXU²OLTXLGHTXLOLEULXPFDOFXODWLRQVLQGLFDWHGWKDWDWWKLVSUHVVXUHHYHQDW * /<&(52/$&(7$/6352'8&7,21%< 6 ,08/$7(' 0 29,1* % (' 5 ($&725     WKHKLJKHURSHUDWLQJWHPSHUDWXUHWKHPRODUDPRXQWRIWKHUHDFWLRQPHGLXPVSHFLHVLQWKH YDSRXU SKDVH ZRXOG QRW H[FHHG  RI WKH WRWDO PRODU DPRXQW LQWURGXFHG LQ WKH UHDFWRU DQGWKHUHIRUHWKHYDSRXUSKDVHZRXOGEHPDLQO\FRQVWLWXWHGE\KHOLXP  7DEOH.LQHWLFH[SHULPHQWVRSHUDWLQJFRQGLWLRQV ([S 1R 6WLUULQJ VSHHGUSP 7HPSHUDWXUH . ,QLWLDOUHDFWDQWV PRODUUDWLR 6ROYHQWPRODU IUDFWLRQQQ &DWDO\VW ORDGLQJZW                                                        6DPSOHVZHUHFROOHFWHGDWSUHGHILQHGWLPHLQWHUYDOVDQGDQDO\VHGE\JDVFKURPDWRJUDSK\ DVGHVFULEHGLQVHFWLRQ(DFKUHDFWLRQNLQHWLFH[SHULPHQWZDVSHUIRUPHGRQO\RQFHLQ RUGHUWRNHHSWKHWHVWVPDQDJHDEOHDQGGXHWRKLJKUHDFWDQWVFRQVXPSWLRQ  $QDO\WLFDO0HWKRGV 6DPSOHVFROOHFWHGLQWKHUHDFWLRQVROYHQWVFUHHQLQJSURFHGXUHGHILQHGLQVHFWLRQ ZHUHDQDO\VHGLQDJDVFKURPDWRJUDSK6KLPDG]X*&3OXVXVLQJDWKHUPDOFRQGXFWLYLW\ GHWHFWRU+HOLXP1  PLQ P/ − ⋅ ZDVXVHGDVWKHFDUULHUJDVIRUWKHVHSDUDWLRQRIWKH FRPSRXQGVLQ D&3:D[&% FROXPQZLWKDOHQJWKRI P  PP  RI LQWHUQDO GLDPHWHU DQG D ILOP WKLFNQHVV RI  P µ  7KH SURSHU FROXPQ WHPSHUDWXUH SURJUDP ZDV GHILQHG IRU HDFKVROYHQW 7KH VDPH JDV FKURPDWRJUDSK\ HTXLSPHQW ZDV XVHG IRU WKH DQDO\VLV RI WKH VDPSOHV FROOHFWHGLQWKHGHWDLOHG NLQHWLFVWXG\RIWKHDFHWDOL]DWLRQUHDFWLRQLQWKHSUHVHQFHRIWKH VHOHFWHGVROYHQWGHVFULEHGLQVHFWLRQ7KHDQDO\VHVZHUHSHUIRUPHGE\LQMHFWLQJ / µ RIVDPSOHWRZKLFKDVSOLWUDWLRRIZDVDSSOLHG7KHWHPSHUDWXUHVRIWKHLQMHFWRU DQGWKHWKHUPDOFRQGXFWLYLW\GHWHFWRUZHUHVHWWR . 7KHFROXPQZDVLQLWLDOO\NHSWDW  .  IRU  PLQ  DQG LWV WHPSHUDWXUH ZDV WKHQ LQFUHDVHG DW D UDWH RI   . PLQ − ⋅  XQWLO LW UHDFKHG . DQGKHOGFRQVWDQWDWWKDWYDOXHIRUWKHIROORZLQJ PLQ $IWHUWKLVSHULRGWKH 6 (/(&7,212)$ 6 2/9(17)25$1 , 17(*5$7(' 5 ($&7,9( ²$ '62537,9( 3 52&(66)257+( 6 <17+(6,62) *($    FROXPQWHPSHUDWXUHZDVGHFUHDVHGWR . DWDUDWHRI  . PLQ − ⋅ 7KHWRWDODQDO\VLVWLPH ZDV PLQ +HOLXP1DWDIORZUDWHRI  PLQ P/ − ⋅ ZDVDOVRXVHGDVWKHFDUULHUJDV   6ROYHQW6HOHFWLRQ6WUDWHJ\IRU5HDFWLYH $GVRUSWLYH,QWHJUDWHG3URFHVVHV $V SUHYLRXVO\ VWDWHG QRQH RI WKH UHDFWDQWV RI WKH *($ V\QWKHVLV E\ PHDQV RI DQ DFHWDOL]DWLRQ UHDFWLRQ FDQ EH XVHG DV VROYHQW LQ WKH 60%5 WHFKQRORJ\ GXH WR SK\VLFDO RU FKHPLFDOFRQVWUDLQV7KHUHIRUHDWZRVWDJHPHWKRGRORJ\ZDVGHYHORSHGDQGDSSOLHGIRUWKH VHOHFWLRQRIWKHPRVWVXLWDEOHVROYHQWIRUWKHSURGXFWLRQRIWKLVDFHWDOE\UHDFWLYH²DGVRUSWLYH SURFHVVHV 7KH PHWKRGRORJ\ FRPSULVHV D WKHRUHWLFDO UDWLQJ SURFHGXUH DLPLQJ WKH LGHQWLILFDWLRQ RI FRPPRQ VROYHQWV XVHG LQ VLPLODU SURFHVVHV EDVHG RQ DQ H[WHQVLYH ELEOLRJUDSKLFUHVHDUFKRIWKHLUSURSHUWLHVDQGDSSOLFDWLRQV7KHQDVKRUWHUOLVWRISRWHQWLDO VROYHQWV ZDV VXEMHFWHG WR D ULJRURXV SHUIRUPDQFH HYDOXDWLRQ LQ D VHW RI H[SHULPHQWV WR GHWHUPLQHWKHLPSDFWRIWKHLUXVHLQWKHILQDO*($SURGXFWLRQSURFHVV )RU WKLV SXUSRVH D W\SLFDO VHW RI RSHUDWLQJ FRQGLWLRQV ZDV GHILQHG 7KH SURFHVV WHPSHUDWXUH ZDV VHW WR  .  DW D SUHVVXUH RI  EDU  DQG DQ LQLWLDO UHDFWLRQ PHGLXP FRPSRVLWLRQ RI  LQ WHUPV RI PRODU IUDFWLRQV RI DFHWDOGHK\GH JO\FHURO DQG VROYHQWUHVSHFWLYHO\ZDVHVWDEOLVKHG  7KHRUHWLFDO%DVHG6ROYHQW6FUHHQLQJ ,Q WKLV VWHS RI WKH VROYHQW VFUHHQLQJ PHWKRGRORJ\ D SULPDU\ OLVW RI DSSUR[LPDWHO\  VROYHQWVZDVHODERUDWHG 7DEOHDQGWKHQVHTXHQWLDOO\UHGXFHGFRQVLGHULQJWKUHHPDMRU SURFHVV YDULDEOHV VROYHQW UHDFWLYLW\ VROYHQW SK\VLFDO VWDWH DW WKH UHDFWLRQ FRQGLWLRQV DQG K\SRWKHWLFDOSKDVHVSOLWSURPRWHGE\WKHXVHRIWKHVROYHQW6XEVHTXHQWO\DUDWLQJV\VWHP VSHFLILFDOO\GHYHORSHGIRUWKHHYDOXDWLRQRIWKHSRWHQWLDORIDFRPSRXQGWRDFWDVVROYHQWLQD UHDFWLYHDGVRUSWLYH SURFHVV ZDV DSSOLHG WR WKH UHGXFHG VROYHQW OLVW $V D UHVXOW WKUHH SRWHQWLDOXVHIXOVROYHQWVZHUHLGHQWLILHG  * /<&(52/$&(7$/6352'8&7,21%< 6 ,08/$7(' 0 29,1* % (' 5 ($&725     7DEOH²3ULPDU\OLVWRIVROYHQWV 6ROYHQW &$61R 6ROYHQW &$61R 6ROYHQW &$61R 7ULFKORURWULIOXRURHWKDQH  %XW\ODFHWDWH  /DFWLFDFLG  7ULFKORUREHQ]HQH  %XW\OFKORULGH  0HWKDQRO  GLFKORUREHQ]HQH  &KORUREHQ]HQH  0HWK\ODFHWDWH  'LPHWKR[\HWKDQH  &KORURIRUP    0HWK\OHWK\ONHWRQH  WULPHWK\OEHQ]HQH  &LWULFDFLG  0HWK\OLVRDP\ONHWRQH  GLFKORUREHQ]HQH  &\FORKH[DQH    0HWK\OLVREXW\ONHWRQH  GLR[RODQH  &\FORKH[DQRO  0HWK\OQSURS\ONHWRQH  GLR[DQH     &\FORKH[DQRQH  0HWK\OWHUWEXW\OHWKHU  EXWDQRO  &\FORSHQWDQH  0HWK\OS\UUROLGRQH  KHSWDQRO  'HFDQH  QQGLPHWK\OIRUPDPLGH    KH[DQRO  'LEURPRPHWKDQH  QEXW\UDOGHK\GH  KH[HQH  'LFKORURPHWKDQH    1RQDQH  KH[\QH  'LHWK\OHWKHU  2FWDQH  RFWDQRO  'LHWK\OHQHJO\FRO  RGLFKORUREHQ]HQH  SHQWDQRO  'LPHWK\ODFHWDPLGH  2[DOLFDFLG  SURSDQRO  'LPHWK\OFDUERQDWH  R[\OHQH  DPLQRHWKDQRO  'LPHWK\OVXOIR[LGH    3HQWDQH  EXWDQRO  'RGHFDQH  3URSLRQDOGHK\GH  EXWDQRQH  (WKDQRO  3URS\OHQHFDUERQDWH  PHWK\OEXWDQH  (WK\O$FHWDWH  S[\OHQH  SHQWDQRO  (WK\OHQHFDUERQDWH  3\ULGLQH  SHQWDQRQH  (WK\OHQHGLFKORULGH  WHUWEXW\ODOFRKRO  SURSDQRO  (WK\OHQHJO\FRO  WHUWEXW\OPHWK\OHWKHU  SHQWDQRO  )RUPDOGHK\GH  WHWUDFKORURPHWKDQH  SHQWDQRQH  )RUPLFDFLG  7HWUDK\GURIXUDQ    $FHWLFDFLG  *O\FHURO  7ROXHQH    $FHWRQH  +HSWDQH  7ULHWK\ODPLQH  $FHWRQLWULOH    +H[DQH    7ULIOXRURDFHWLFDFLG  $FU\ORQLWULOH  ,VREXWDQRO  9DOHUDOGHK\GH  %HQ]HQH    ,VREXW\UDOGHK\GH  :DWHU  %HQ]RQLWULOH  ,VRRFWDQH    %HQ]\ODOFRKRO  ,VRSURS\ODFHWDWH    6ROYHQWVXVHGLQSUHYLRXVDFHWDOL]DWLRQUHDFWLRQVWXGLHV  )RFXVLQJRQ3UHGLFWDEO\6XLWDEOH6ROYHQWV 7DNLQJ LQWR FRQVLGHUDWLRQ WKH GHYHORSPHQW RI D SURFHVV IRU WKH SURGXFWLRQ RI *($ E\ 60%5VROYHQWVWKDWKDYHEHHQUHSRUWHGDVUHDFWLYHZLWKDQ\RIWKHUHDFWDQWVRUSURGXFWVRI 6 (/(&7,212)$ 6 2/9(17)25$1 , 17(*5$7(' 5 ($&7,9( ²$ '62537,9( 3 52&(66)257+( 6 <17+(6,62) *($    WKHVHOHFWHGV\QWKHVLVURXWHVXFKDVDOFRKROVDOGHK\GHVNHWRQHVDQGFDUER[\OLFDFLGVZHUH FRQVLGHUHGDVXQVXLWDEOHIRUWKHSURFHVVLQWHQGHGWREHLPSOHPHQWHGDQGFRQVHTXHQWO\ZHUH HOLPLQDWHGIURPWKHSULPDU\OLVW 'XH WR RSHUDWLRQDO UHTXLUHPHQWV RI WKH 60%5 XQLW WKH VROYHQW WR EH XVHG VKRXOG SUHIHUDEO\ EH DW WKHOLTXLG VWDWH 0DNLQJ XVHRI SXEOLVKHG GDWD LQWKH RSHQ OLWHUDWXUH WKH PHOWLQJ SRLQW RI HDFK VROYHQW ZDV FRPSLOHG DQG LWV ERLOLQJ SRLQW GHWHUPLQHG WKURXJK WKH $QWRLQHHTXDWLRQ  DWWKHSUHYLRXVO\PHQWLRQHGSUHVVXUHYDOXHV$SSO\LQJDVDIHW\IDFWRURI ±  .  WR WKH SKDVH FKDQJH WHPSHUDWXUHV FRQVLGHUHG WKH VROYHQWV IRU ZKLFK WKH PHOWLQJ SRLQW ZDV DERYH  .  DQG WKH ERLOLQJ SRLQW ZDV EHORZ  .  ZHUH H[FOXGHG IURP WKH VFUHHQLQJ ,Q WKH IROORZLQJ VROYHQW VFUHHQLQJ VWHS D VWXG\ ZDV FDUULHG RXW LQ RUGHU WR DYRLG WKH DGGLWLRQ RI DQRWKHU PDVV WUDQVIHU UHVLVWDQFH WKURXJK WKH SURPRWLRQ RI WKH IRUPDWLRQ RI PXOWLSOHSKDVHV\VWHPV$VSHQ3OXV  VRIWZDUHZDVXVHGWRHVWLPDWHPLVFLELOLW\RIWKHVROYHQW ZLWKWKHLQLWLDOUHDFWLRQPHGLXPDWWKHGHILQHGRSHUDWLQJFRQGLWLRQVFRQVLGHULQJWKH81,)$& PRGHOIRUFRPSXWLQJWKHDFWLYLW\RIHDFKVSHFLHV,IWKHDUHDRIWKHPLVFLELOLW\UHJLRQRIWKH WHUQDU\SKDVHGLDJUDPIRUDVSHFLILFVROYHQWZDVORZHUWKDQWKDWVROYHQWZDVH[FOXGHG IURP WKH VROYHQWV OLVW ,W PXVW EH QRWLFHG WKDW GXH WR ODFN RI GDWD IRU GLR[RODQH FKORURIRUP GLPHWK\O VXOIR[LGH DQG QQGLPHWK\OIRUPDPLGH WKHVH VROYHQWV FRXOG QRW EH H[FOXGHG $IWHUWKHDSSOLFDWLRQRIWKHFULWHULDHVWDEOLVKHGIRUWKHVHTXHQWLDOHOLPLQDWLRQRIVROYHQWV IURPWKHOLVWSUHVHQWHGLQ7DEOHLWZDVSRVVLEOHWRLGHQWLI\DVKRUWHUOLVWRISUHGLFWDEO\ XVHIXO VROYHQWV FRPSULVLQJ GLPHWKR[\HWKDQH GLR[RODQH GLR[DQH DFHWRQLWULOH DFU\ORQLWULOH FKORURIRUP GLFKORURPHWKDQH GLPHWK\O FDUERQDWH GLPHWK\O VXOIR[LGH HWK\O DFHWDWHPHWK\ODFHWDWHQQGLPHWK\OIRUPDPLGHWHWUDFKORURPHWKDQHDQGWHWUDK\GURIXUDQ  6ROYHQWV5DWLQJE\LWV3UHGLFWHG3URFHVV3HUIRUPDQFHDQG,PSDFW :KHQ GHVLJQLQJ DQ LQGXVWULDO SURFHVV WZR PDLQ TXHVWLRQV PXVW EH FRQVLGHUHG SURFHVV SHUIRUPDQFHDQGSURFHVVLPSDFW 5HJDUGLQJ WKHVWXGLHGSURFHVVWKHDFHWDOL]DWLRQUHDFWLRQFDWDO\VHGE\ DQLRQH[FKDQJH UHVLQ LQ D 60%5 XQLW RQH FDQ SURPSWO\ FRQFOXGH WKDW SRODULW\ ZLOO EH D NH\ SHUIRUPDQFH SDUDPHWHU2QRQHKDQGDKLJKO\SRODUPHGLXPIDYRXUVWKHDFHWDOL]DWLRQUHDFWLRQRQFHLWV UDWHGHWHUPLQLQJVWHSLVWKHIRUPDWLRQRIDFDWLRQIURPWKHSURWRQDWHGKHPLDFHWDO  DQGD SRODUPHGLDDOORZVWKHVWDELOL]DWLRQRIWKHLQWHUPHGLDWHFDWLRQV  2QWKHRWKHUKDQGDVDQ LRQH[FKDQJHUHVLQZLOOEHXVHGDVFDWDO\VWDGVRUEHQWWKHVRUSWLRQSURSHUWLHVRIWKHVROYHQWV FDQ EH URXJKO\ DSSUR[LPDWHG E\ WKHLU SRODULW\ :DWHU LV D KLJKO\ SRODU FRPSRXQG DQG ZLOO DGVRUELQODUJHDPRXQWVLQ$PEHUO\VWWKXVWKHGHFUHDVHRIVROYHQWFRQVXPSWLRQWKDWZLOO DFWDVGHVRUEHQWLQWKH60%5SURFHVVZLOOEHIDYRXUHGLIDKLJKO\SRODUVROYHQWLVFKRVHQ,Q * /<&(52/$&(7$/6352'8&7,21%< 6 ,08/$7(' 0 29,1* % (' 5 ($&725      )LJXUH       (IIHFWRIWKHVWLUULQJVSHHGLQWKHUHDFWLRQUDWHDVDPHDVXUHPHQWRIH[WHUQDO PDVVWUDQVIHUOLPLWDWLRQV  7 . =   3 EDU = LQLWLDODFHWDOGHK\GHJO\FHUROPRODU UDWLRVROYHQWPRODUIUDFWLRQRI  ZW RIXQVLHYHG$PEHUO\VWVWLUULQJVSHHGRI USP   1R VLJQLILFDQW GLIIHUHQFHV DUH REVHUYHG LQ WKH NLQHWLF EHKDYLRXU RI WKH H[SHULHQFHV SUHVHQWHGLQ)LJXUH7KHUHIRUHRQHFDQDVVXPHWKDWVHWWLQJDVWLUULQJVSHHGRI USP  ZLOOHOLPLQDWHWKHH[WHUQDOUHVLVWDQFHVWRPDVVWUDQVIHU 7KH LQWURGXFWLRQ RI DQ LQHUW VROYHQW LQ D UHDFWLRQ PHGLD FDQ OHDG WR FKDQJHV LQ WKH LQWUDSDUWLFOH GLIIXVLRQ RI WKH VSHFLHV LQVLGH WKH FDWDO\VW SRUHV +RZHYHU FRQVLGHULQJ WKH SK\VLFDO SURSHUWLHV PDLQO\ YLVFRVLW\ PRODU YROXPH DQG PRODU PDVV RI WKH VROYHQW UHDFWDQWVDQGSURGXFWVRIWKHDFHWDOL]DWLRQLWLVQRWUHDVRQDEOHWRDGPLWWKDWWKHLQWHUQDO PDVV WUDQVIHU UHVLVWDQFHV REVHUYHG IRU WKH VROYHQWIUHH UHDFWLRQ ZLOO EHFRPH QHJOLJLEOH 7KHUHIRUHIRUWKHPDWKHPDWLFDOPRGHOGHYHORSHGZLOOWDNHWKLVIDFWRULQWRDFFRXQW  0DWKHPDWLFDO0RGHODQG1XPHULFDO6ROXWLRQ $FRPSOHWHPDWKHPDWLFDOPRGHORIDEDWFKUHDFWRURSHUDWLQJXQGHULVRWKHUPDOFRQGLWLRQV LQWKHDEVHQFHRIH[WHUQDOPDVVWUDQVIHUUHVLVWDQFHVEXWLQFOXGLQJWKHLQWUDSDUWLFOHGLIIXVLRQ RI WKH VSHFLHV DQG WKH WHPSHUDWXUH GHSHQGHQFH RI WKH UHDFWLRQ NLQHWLF HTXLOLEULXP DQG DGVRUSWLRQFRQVWDQWVWKURXJKWKH$UUKHQLXVDQG9DQ·W+RIIODZVUHVSHFWLYHO\ZDVGHYHORSHG VLPLODUO\WRWKHPRGHOIRUWKHVROYHQWIUHHDFHWDOL]DWLRQUHDFWLRQSUHVHQWHGLQ6HFWLRQ (TXDWLRQVWR Ϭй ϭϬй ϮϬй ϯϬй ϰϬй ϱϬй ϲϬй ϳϬй Ϭ ϭϬϬ ϮϬϬ ϯϬϬ ϰϬϬ ϱϬϬ ϲϬϬ ŽŶǀĞƌƐŝŽŶ dŝŵĞ;ŵŝŶͿ ϳϬϬƌƉŵ ϱϬϬƌƉŵ 6 (/(&7,212)$ 6 2/9(17)25$1 , 17(*5$7(' 5 ($&7,9( ²$ '62537,9( 3 52&(66)257+( 6 <17+(6,62) *($    2QO\WZRVOLJKWDGMXVWPHQWVZHUHPDGHWRWKHSULRUPRGHOUHJDUGLQJWKHDGGLWLRQRI'062 WRWKHUHDFWLRQV\VWHP 7KHILUVWPRGLILFDWLRQLVUHODWHGWRWKHQRQLGHDOEHKDYLRXURIWKHVWXGLHGPL[WXUH7KH DSSOLFDWLRQRIWKH81,)$&PRGHODVLQWKHSUHYLRXVFKDSWHULVLPSRVVLEOHVLQFHWKHELQDU\ LQWHUDFWLRQ SDUDPHWHU EHWZHHQ WKH DOGHK\GH JURXS DQG '062 LV QRW DYDLODEOH LQ WKH RSHQ OLWHUDWXUH 7KH ODFN RI ELQDU\ LQWHUDFWLRQ SDUDPHWHUV IRU V\VWHPV LQYROYLQJ *($ PDNHV LW LPSRVVLEOH WR GHWHUPLQH WKH DFWLYLW\ FRHIILFLHQWV RI HDFK VSHFLHV WKURXJK RWKHU FRPPRQ PHWKRGVVXFKDV:LOVRQ157/RU81,48$&  7KHUHIRUHVLQFHLWZDVLPSRVVLEOHWRSUHGLFWWKH GHYLDWLRQVRIWKHPL[WXUHIURPWKHLGHDOEHKDYLRXUWKURXJKWKHLQWURGXFWLRQRIWKHDFWLYLW\ FRHIILFLHQW IRU HDFK VSHFLHV WKH PRGHO HTXDWLRQV ZHUH VROYHG LQ WHUPV RI FRQFHQWUDWLRQV 7KLVLPSOLHGWKHUHFDOFXODWLRQRIWKHHTXLOLEULXPFRQVWDQWEDVHGRQFRQFHQWUDWLRQVIURPWKH GDWD SUHVHQWHG LQ VHFWLRQ  &RQVLGHULQJ WKLV WKH QHZ YDOXH HVWLPDWHG IRU WKH VWDQGDUG UHDFWLRQ*LEEVIUHHHQHUJ\ZDV  NPRO − ⋅ 7KH VHFRQG PRGLILFDWLRQ ZDV LQWURGXFHG LQ WKH UHDFWLRQ UDWH ODZ $OWKRXJK WKH VDPH UHDFWLRQ UDWH PRGHO ZDV DGPLWWHG WKH /DQJPXLU+LQVKHOZRRG+RXJHQ:DWVRQ /++: GLIIHUHQW FRQVLGHUDWLRQV KDG WR EH DVVXPHG ZLWK UHVSHFW WR WKH DGVRUSWLRQ RI WKH VSHFLHV 7KLV PRGHO DVVXPHV WKH DGVRUSWLRQ RI ERWK UHDFWDQWV IROORZHG E\ D VXUIDFH UHDFWLRQ WKDW RULJLQDWHVDKHPLDFHWDOFRQVLGHUHGDVWKHUDWHGHWHUPLQLQJVWHS7ZRVXEVHTXHQWVXUIDFH UHDFWLRQVZLOOOHDGWRWKHIRUPDWLRQRIDGVRUEHGZDWHUDQGDFHWDODQGWKHILQDOVWHSLVWKH GHVRUSWLRQ RI ERWK SURGXFWV ,Q WKH SUHYLRXV FKDSWHU IROORZLQJ D SURFHGXUH VXJJHVWHG E\ VHYHUDO DXWKRUV IRU RWKHU DFHWDOL]DWLRQV  RQO\ ZDWHU DGVRUSWLRQ ZDV WDNHQ LQWR DFFRXQW VLQFH WKLV FRPSRXQG DGVRUSWLRQ LV VLJQLILFDQWO\ KLJKHU WKDQ WKDW RI WKH UHPDLQLQJ UHDFWLRQ VSHFLHV +RZHYHU IRU WKLV V\VWHP DV '062 LV WKH PDMRU FRPSRXQG DQG LW LV D YHU\ SRODU VROYHQWZKLFKLQGLFDWHVWKDWLWZLOODGVRUEVWURQJO\RQ$PEHUO\VWLWVDGVRUSWLRQPXVWDOVR EH FRQVLGHUHG 7KHUHIRUH WKH UHDFWLRQ UDWH ODZ SUHVHQWHG LQ HTXDWLRQ  ZDV PRGLILHG DFFRUGLQJWRHTXDWLRQ  ( ) 2 , , 1 § · − ¨ ¸ ¨ ¸ © ¹ ℜ = + + GEA W Ac Gly eq c s W W s D D C C C C K k K C K C    ,QWKLVHTXDWLRQ ℜ UHSUHVHQWVWKHUHDFWLRQUDWHEDVHGRQORFDOLQWUDSDUWLFOHFRPSRVLWLRQ RI DFHWDOGHK\GH JO\FHURO *($ ZDWHU DQG '062 $FHW & *O\ &  *($ & : &  DQG ' &  UHVSHFWLYHO\  V : . DQG  V ' . UHSUHVHQWZDWHUDQG'062DGVRUSWLRQHTXLOLEULXPFRQVWDQWV7KH GHSHQGHQFHRI'062DGVRUSWLRQHTXLOLEULXPFRQVWDQWFDQDOVREHH[SUHVVHGE\WKH9DQ·W+RII ODZDVVKRZQLQHTXDWLRQ  * /<&(52/$&(7$/6352'8&7,21%< 6 ,08/$7(' 0 29,1* % (' 5 ($&725     0 , , , exp s D s D s D H K K RT ∆ § · = − ¨ ¸ © ¹   7KHYDULDEOH   V ' . UHSUHVHQWWKH9DQ·W+RIIHTXDWLRQSUHH[SRQHQWLDOIDFWRUIRU'062 DQG  V ' + ∆ UHSUHVHQWV'062DGVRUSWLRQHQWKDOS\ 7KH PRGHO HTXDWLRQV ZHUH VROYHG ZLWK J35206 *HQHUDO 3URFHVV 0RGHOOLQJ 6\VWHP YHUVLRQXVLQJRQHRILWVLQWHJUDWHGVROYHUV'$62/9GLVFUHWLVLQJWKHUDGLDOGLPHQVLRQLQ QRQXQLIRUPLQWHUYDOVDQGPDNLQJXVHRIDVHFRQGRUGHUFHQWUHGILQLWHGLIIHUHQFHPHWKRG 7KH GHWHUPLQDWLRQ RI WKH XQNQRZQ SDUDPHWHUV D (   F N  : V +∆   V ' + ∆   : V .  DQG   V ' .  ZDVFDUULHGRXWXVLQJWKH´3DUDPHWHU(VWLPDWLRQµWRRODQGILWWLQJWKHH[SHULPHQWDOGDWDE\ WKH PD[LPXPOLNHOLKRRG PHWKRG DVVXPLQJ D FRQVWDQW YDULDQFH PRGHO DQG VHWWLQJ WKH HVWLPDWLRQWROHUDQFHWR   −  )RUWKHGHWHUPLQDWLRQRIWKHHUURUVDVVRFLDWHGWRWKHSDUDPHWHUVHVWLPDWHGD-DFNNQLIH PHWKRGRORJ\  ZDVDSSOLHGFRQVLGHULQJJURXSVRIH[SHULPHQWVZKHUHRQHH[SHULPHQWZDV UHPRYHGIURPWKHRULJLQDOVHWRIH[SHULPHQWVH[SHULPHQWZDVQRWWDNHQLQWRDFFRXQWVLQFH QRH[WHUQDOPDVVWUDQVIHUOLPLWDWLRQVZHUHREVHUYHGDQGWKHUHIRUHWKHUHVXOWVDUHVLPLODUWR WKRVH REWDLQHG LQ H[SHULPHQW  DQG LW ZDV FRQVLGHUHG WKDW WKH VDPH ´ZHLJKWµ VKRXOG EH JLYHQ WR HYHU\ H[SHULPHQW UHSUHVHQWLQJ D XQLTXH VHW RI RSHUDWLQJ FRQGLWLRQV RQ WKH SDUDPHWHUHVWLPDWLRQSURFHGXUH  .LQHWLF3DUDPHWHUV(VWLPDWLRQ ,Q RUGHU WR PDNH D PRUH REMHFWLYH DVVHVVPHQW RI WKH TXDOLW\ RI WKH ILWWLQJ RI WKH H[SHULPHQWV FRQVLGHULQJ WKH SDUDPHWHUV HVWLPDWHG IRU WKH PDWKHPDWLFDO PRGHO LPSOHPHQWHGLWVFRUUHODWLRQFRHIILFLHQW  &RUUHO 5 ZDVFRPSXWHGDFFRUGLQJWRHTXDWLRQ  ( ) () 2 exp mod , , 1 1 2 2 exp exp , 1 1 1 = = = = − = − − ¦¦ ¦¦ NE NP i j i j i j Correl NE NP i j i j X X R X X   ZKHUH H[S MN ; DQG PRG MN ; DUHWKH WK N PHDVXUHGDQGSUHGLFWHGYDOXHVUHVSHFWLYHO\IRUWKH FRQYHUVLRQLQH[SHULPHQW M  H[S ; LVWKHDYHUDJHWKHH[SHULPHQWDOFRQYHUVLRQYDOXHV 1( LV 6 (/(&7,212)$ 6 2/9(17)25$1 , 17(*5$7(' 5 ($&7,9( ²$ '62537,9( 3 52&(66)257+( 6 <17+(6,62) *($    WKH QXPEHU RI H[SHULPHQWV SHUIRUPHG DQG 13  LV WKH QXPEHU RI GDWD SRLQWV FROOHFWHG SHU H[SHULPHQW 0DNLQJ XVH RI WKH NLQHWLF GDWD JDWKHUHG WKURXJK WKH H[SHULPHQWDO SDUDPHWULF VWXG\ VXPPDUL]HG LQ 7DEOH  DQG FRQVLGHULQJ WKH PDWKHPDWLFDO PRGHO DQG LWV QXPHULFDO UHVROXWLRQDVGHVFULEHGLQ6HFWLRQLWZDVSRVVLEOHWRHVWLPDWHWKHNLQHWLFSDUDPHWHUV SUHVHQWHGLQ7DEOH  7DEOH.LQHWLFSDUDPHWHUVHVWLPDWHGIRUWKHDFHWDOL]DWLRQRIJO\FHUROLQSUHVHQFHRI '062 3DUDPHWHUXQLWV (VWLPDWHG9DOXH 6WDQGDUG(UURU ( )  D ( NPRO − ⋅    ( )      F FDW N GP PRO J V − − − ⋅ ⋅ ⋅  [   [   ( )  V : + NPRO − ∆ ⋅   ( )  V ' + NPRO − ∆ ⋅   ( )    V : . GP PRO − ⋅ [   [   ( )    V ' . GP PRO − ⋅ [   [    $VLWFDQEHREVHUYHGIURPWKHYDOXHVSUHVHQWHGLQ7DEOHWKHHVWLPDWLRQRIWKHVL[ SDUDPHWHUVIRUWKHSUHYLRXVO\GHVFULEHGPRGHOOHGWRODUJHVWDQGDUGHUURUV)RULQVWDQFHWKH VWDQGDUGHUURUVIRUWKHSUHH[SRQHQWLDOIDFWRUVIURPWKH$UUKHQLXVDQGWKH9DQ·W+RIIODZV DFKLHYHGDSSUR[LPDWHO\RILWVDEVROXWHYDOXHV)XUWKHUPRUHFRQWUDU\WRWKHH[SHFWHG WKH HVWLPDWLRQ SURFHGXUH VXJJHVWHG WKDW '062 FRXOG KDYH D KLJKHU DGVRUSWLRQ HTXLOLEULXP FRQVWDQW WKDQ ZDWHU UHJDUGOHVV WKH SDUDPHWHUV HVWLPDWLRQ HUURUV ZKLFK LV QRW WUXH IRU $PEHUO\VW DV LQGLFDWHG E\ WKH VZHOOLQJ WHVWV SUHVHQWHG LQ 6HFWLRQ  7KXV WKH VROXWLRQIRXQGWRHQKDQFHWKHNLQHWLFSDUDPHWHUVHVWLPDWLRQSUHFLVLRQDQGDWWHPSWWRDYRLG WKH LQFRQVLVWHQFLHV SUHVHQWHG FRPSULVHG WKH UHGXFWLRQ RI WKH QXPEHU RI SDUDPHWHUV WR EH GHWHUPLQHG 6LQFHWKHUDQJHRIRSHUDWLQJWHPSHUDWXUHVFDQEHFRQVLGHUHGQDUURZ . WKHHIIHFWRI WHPSHUDWXUHRQWKHDGVRUSWLRQHTXLOLEULXPZDVFRQVLGHUHGQHJOLJLEOHDQGHTXDWLRQVDQG ZHUHUHPRYHGIURPWKHILQDOPRGHO7KLVDVVXPSWLRQZDVEDVHGRQWKHUHVXOWVSXEOLVKHG IRURWKHUDFHWDOL]DWLRQUHDFWLRQVEHWZHHQDFHWDOGHK\GHDQGVHYHUDODOFRKROVGHVFULEHGE\D /++: UDWH ODZ   LQ ZKLFK LW LV SRVVLEOH WR REVHUYH D PRUH VLJQLILFDQW WHPSHUDWXUH GHSHQGHQFHRIWKHNLQHWLFFRQVWDQWZKHQFRPSDUHGWRWKHDGVRUSWLRQFRQVWDQW)RULQVWDQFH IRUWKHDFHWDOL]DWLRQOHDGLQJWRWKHV\QWKHVLVRI'%(  FRQVLGHULQJDWHPSHUDWXUHUDQJHIURP  . WR . WKHZDWHUDGVRUSWLRQFRQVWDQWLVH[SHFWHGWRGHFUHDVHWRDSSUR[LPDWHO\RQH * /<&(52/$&(7$/6352'8&7,21%< 6 ,08/$7(' 0 29,1* % (' 5 ($&725     WKLUGRILWVYDOXHZKLOHWKHLQFUHDVHRIWKHUHDFWLRQNLQHWLFFRQVWDQWUHDFKHVWHQWLPHVLWV YDOXHIURPWKHORZHUWRWKHKLJKHUWHPSHUDWXUH+HQFHWKHQHZYDOXHVHVWLPDWHGIRUWKH VLPSOLILHGPRGHOSDUDPHWHUV D (   F N  : V . DQG  V ' . DUHSUHVHQWHGLQ7DEOH  7DEOH²&RUUHFWHGHVWLPDWLRQRIWKHNLQHWLFSDUDPHWHUVIRUWKHDFHWDOL]DWLRQRIJO\FHUROLQ SUHVHQFHRI'062 3DUDPHWHUXQLWV (VWLPDWHG9DOXH 6WDQGDUG(UURU ( )  D ( NPRO − ⋅    ( )      F FDW N GP PRO J V − − − ⋅ ⋅ ⋅  [   [   ( )   V : . GP PRO − ⋅ [   [   ( )   V ' . GP PRO − ⋅ [   [     7KH YDOXH GHWHUPLQHG IRU WKH ILWWLQJ FRUUHODWLRQ FRHIILFLHQW XVLQJ WKH SDUDPHWHUV SUHVHQWHGLQ7DEOHZDVLQGLFDWLQJWKDWWKHPRGHOGHVFULEHVZLWKKLJKDFFXUDF\WKH NLQHWLF EHKDYLRXU RI WKLV UHDFWLRQ RYHU WKH UDQJH RI H[SHULPHQWDO FRQGLWLRQV WHVWHG 7KH HVWLPDWHGSDUDPHWHUVSUHFLVLRQZDVFRQVLGHUDEO\LPSURYHGZLWKDQHUURURIDSSUR[LPDWHO\ DVVRFLDWHGWRWKHGHWHUPLQDWLRQRIWKHUHDFWLRQDFWLYDWLRQHQHUJ\DQGDPD[LPXPHUURURI DSSUR[LPDWHO\IRUWKH$UUKHQLXVSUHH[SRQHQWLDOIDFWRU $GLYHUJHQFHLVREVHUYHGZKHQFRPSDULQJWKHUHDFWLRQDFWLYDWLRQHQHUJ\REWDLQHGIRUWKH V\QWKHVLV RI *($ LQ WKH SUHVHQFH RI '062 DQG WKH VROYHQWIUHH UHDFWLRQ UHSRUWHG LQ WKH SUHYLRXVFKDSWHUIRUZKLFKDYDOXHRI  NPRO − ⋅ZDVHVWLPDWHG7KLVGHYLDWLRQPLJKW UHOD\ LQ VHYHUDO IDFWRUV )LUVWRI DOOWKH IRUPHU PRGHO LQ WKH DEVHQFH RI WKHVROYHQW KDV EHHQGHVFULEHGLQWHUPVRIDFWLYLWLHVZKLOHWKHPRGHOIRUWKLVQHZV\VWHPGRHVQRWDFFRXQW IRUWKHQRQLGHDOLW\RIWKHOLTXLGSKDVHGXHWRODFNRISDUDPHWHUVIRUWKHFRPSXWDWLRQRIWKH DFWLYLW\FRHIILFLHQWVDVSUHYLRXVO\GLVFXVVHG$GGLWLRQDOO\WKHLQIOXHQFHRIWKHWHPSHUDWXUH RQWKHDGVRUSWLRQHTXLOLEULXPZDVQRWFRQVLGHUHGIRUWKHUHDFWLRQLQWKHSUHVHQFHRI'062 VLQFHWKHQXPEHURISDUDPHWHUVWREHHVWLPDWHGZRXOGQRWDOORZDFRQVLVWHQWGHWHUPLQDWLRQ RIWKHLUYDOXHV$VDFRQVHTXHQFHWKHHVWLPDWHGDFWLYDWLRQHQHUJ\YDOXHPLJKWKDYHVXIIHUHG VRPH GHYLDWLRQV WR FRPSHQVDWH WKH HIIHFW RI WKH HQWKDOSLHV RI DGVRUSWLRQ LQ WKH UHDFWLRQ UDWH )LQDOO\ WKH KLJK SRODULW\ RI '062 DQG LWV FRUUHVSRQGLQJ DIILQLW\ WRZDUGV WKH UHVLQ PLJKW EH OHDGLQJ WR WKH KLQGHULQJ RI VRPH RI WKH DYDLODEOH DFWLYH VLWHV RI WKH FDWDO\VW GHFUHDVLQJWKHRYHUDOOUHDFWLRQUDWH7KHGLUHFWFRPSDULVRQEHWZHHQWKHDGVRUSWLRQFRQVWDQW YDOXHVKHUHUHSRUWHGDQGWKRVHIRUWKHVROYHQWIUHHV\VWHPLVQRWDOORZHG7KHWZRPRGHOV KDYHGLIIHUHQWFRQVLGHUDWLRQVRYHUWKHQRQLGHDOLW\RIWKHPL[WXUHDQGWKHYDOXHVHVWLPDWHG IRU WKHVH FRQVWDQWV DUH DIIHFWHG E\ WKHP +RZHYHU LW LV LPSRUWDQW WR PHQWLRQ WKDW DV 6 (/(&7,212)$ 6 2/9(17)25$1 , 17(*5$7(' 5 ($&7,9( ²$ '62537,9( 3 52&(66)257+( 6 <17+(6,62) *($    H[SHFWHG GXH WR WKH ZHOONQRZQ KLJK DIILQLW\ RI ZDWHU WRZDUGV LRQ H[FKDQJH UHVLQV DV $PEHUO\VW D KLJKHU DGVRUSWLRQ FDSDFLW\ ZDV HVWLPDWHG IRU ZDWHU WKDQ IRU '062 1HYHUWKHOHVV LW LV LPSRUWDQW WR XQGHUOLQH WKDW QR GLUHFW PHDVXUHPHQW RI WKH DGVRUSWLRQ FRQVWDQWVZDVSHUIRUPHG,QVWHDGWKHYDOXHVSUHVHQWHGZHUHREWDLQHGWKURXJKWKHILWWLQJRI NLQHWLFGDWD,QDQ\FDVHLWLVLQWHQGHGWKDWWKRVHYDOXHVDUHFRKHUHQWEHWZHHQWKHPDQGLI QRWDFFXUDWHDWOHDVWWKH\VKRXOGKDYHVRPHSK\VLFDOPHDQLQJ ,Q WKH VXEVHTXHQW VHFWLRQ D PRUH GHWDLOHG DQDO\VLV RI WKH H[SHULPHQWDO DQG SUHGLFWHG NLQHWLFEHKDYLRXUZLOOEHDGGUHVVHG  (IIHFWRI7HPSHUDWXUH $VGHVFULEHE\WKH$UUKHQLXVODZWKHUHDFWLRQUDWHVKRXOGEHIDYRXUHGE\WKHLQFUHDVHRI WHPSHUDWXUH7KDWWUHQGLVREVHUYHGLQWKHH[SHULPHQWDOUHVXOWVSUHVHQWHGLQ)LJXUH   )LJXUH       (IIHFWRIWHPSHUDWXUHRQWKHUHDFWLRQUDWH  3 EDU = LQLWLDO DFHWDOGHK\GHJO\FHUROPRODUUDWLRVROYHQWPRODUIUDFWLRQRIVWLUULQJVSHHGRI USP   )LJXUHDOVRVKRZVWKDWWKHPRGHOLVDEOHWRGHVFULEHDFFXUDWHO\WKHHIIHFWRIFKDQJHV LQ WKH UHDFWLRQ WHPSHUDWXUH ZLWKLQ D UDQJH IURP  .  WR  .  LQGHSHQGHQWO\ IURP WKH FDWDO\VWORDGLQJ Ϭй ϮϬй ϰϬй ϲϬй ϴϬй ϭϬϬй Ϭ ϭϬϬ ϮϬϬ ϯϬϬ ϰϬϬ ϱϬϬ ŽŶǀĞƌƐŝŽŶ dŝŵĞ;ŵŝŶͿ dсϯϰϯ<ϬϯϬǁƚйĂƚ;džƉͿ dсϯϰϯ<ϬϯϬǁƚйĂƚ;DŽĚĞůͿ dсϯϮϯ<ϬϯϬǁƚйĂƚ;džƉͿ dсϯϮϯ<ϬϯϬǁƚйĂƚ;DŽĚĞůͿ dсϯϮϯ<ϬϭϱǁƚйĂƚ;džƉͿ dсϯϮϯ<ϬϭϱǁƚйĂƚ;DŽĚĞůͿ dсϯϬϯ<ϬϭϱǁƚйĂƚ;džƉͿ dсϯϬϯ<ϬϭϱǁƚйĂƚ;DŽĚĞůͿ * /<&(52/$&(7$/6352'8&7,21%< 6 ,08/$7(' 0 29,1* % (' 5 ($&725     $OWKRXJKWKHHTXLOLEULXPUHVXOWVDUHQRWSUHVHQWHGWRDOORZDEHWWHUXQGHUVWDQGLQJRIWKH NLQHWLFEHKDYLRXUWKURXJKWKHFRQYHUVLRQFXUYHVSUHVHQWHGLWZDVREVHUYHGWKDWHTXLOLEULXP FRQYHUVLRQ GHFUHDVHG ZLWK LQFUHDVLQJ WHPSHUDWXUHV DFFRUGLQJ WR WKH H[SHFWHG IRU DQ H[RWKHUPLFUHDFWLRQDVLVWKHFDVHRIDFHWDOL]DWLRQV  (IIHFWRIWKH5HDFWDQWV0RODU5DWLR 7KH PRGHO KDV DOVR VKRZQ WR EH LQ UHDVRQDEOH DJUHHPHQW ZLWK WKH H[SHULPHQWDO REVHUYDWLRQV ZKHQ FKDQJHV RQ WKH LQLWLDO FRPSRVLWLRQ RI WKH UHDFWLRQ PHGLXP ZHUH SURPRWHG$KLJKHUUHDFWLRQUDWHZDVDFKLHYHGZKHQDQH[FHVVRIHLWKHURIWKHUHDFWDQWVZDV XVHGDVSUHVHQWHGLQ)LJXUHZKHUHWKHUDWHVIRUPL[WXUHVZLWKDQLQLWLDODFHWDOGHK\GHWR JO\FHUROPRODUUDWLRRIDQGDUHSORWWHG   )LJXUH       (IIHFWRIWKHUHDFWDQWVPRODUUDWLRRQWKHUHDFWLRQUDWH  7 . =   3 EDU =  VROYHQWPRODUIUDFWLRQRIVWLUULQJVSHHGRI USP   +RZHYHU JUHDWHU GLIILFXOWLHV DUH REVHUYHG LQ WKH SUHGLFWLRQ RI WKH HIIHFW RI WKLV SDUDPHWHURQWKHNLQHWLFEHKDYLRXUZKHQFRPSDUHGZLWKWKHHIIHFWRIWHPSHUDWXUH7KRVH GHYLDWLRQV PLJKW EH UHODWHG ZLWK WKH PDMRU LPSDFW WKDW FKDQJHV LQ WKH UHDFWLRQ PHGLXP Ϭй ϮϬй ϰϬй ϲϬй ϴϬй ϭϬϬй Ϭ ϭϬϬ ϮϬϬ ϯϬϬ ϰϬϬ ϱϬϬ ŽŶǀĞƌƐŝŽŶ dŝŵĞ;ŵŝŶͿ ƌĂƚŝŽсϮϬϭϬϯϬǁƚйĂƚ;džƉͿ ƌĂƚŝŽсϮϬϭϬϯϬǁƚйĂƚ;DŽĚĞůͿ ƌĂƚŝŽсϭϬϬϬϯϬǁƚйĂƚ;džƉͿ ƌĂƚŝŽсϭϬϬϬϯϬǁƚйĂƚ;DŽĚĞůͿ ƌĂƚŝŽсϬϱϬϬϭϱǁƚйĂƚ;džƉͿ ƌĂƚŝŽсϬϱϬϬϭϱǁƚйĂƚ;DŽĚĞůͿ ƌĂƚŝŽсϭϬϬϬϭϱǁƚйĂƚ;džƉͿ ƌĂƚŝŽсϭϬϬϬϭϱǁƚйĂƚ;DŽĚĞůͿ 6 (/(&7,212)$ 6 2/9(17)25$1 , 17(*5$7(' 5 ($&7,9( ²$ '62537,9( 3 52&(66)257+( 6 <17+(6,62) *($    FRPSRVLWLRQ KDYH RQ WKH DFWLYLW\ FRHIILFLHQWV RI WKH VSHFLHV SUHVHQW LQ WKH PL[WXUH ZKLFK FRXOGQRWEHDFFRXQWHGIRUE\WKHPRGHOGXHWRWKHSUHYLRXVO\PHQWLRQHGUHDVRQV 5HJDUGLQJWKHHIIHFWRIWKHFDWDO\VWORDGLQJLWZDVSRVVLEOHWRYHULI\WKDWDQLQFUHDVHRI RQWKLVYDULDEOHZLOOOHDGWRDQHTXLYDOHQWLQFUHDVHRIWKHH[SHULPHQWDOUHDFWLRQUDWH HVWLPDWHG E\ WKH LQLWLDO UHDFWLRQ UDWH PHWKRG $ VLPLODU EHKDYLRXU ZDV REVHUYHG IRU WKH PRGHOSUHGLFWLRQ  (IIHFWRIWKH6ROYHQW0RODU)UDFWLRQ 7KHGLOXWLRQDSSOLHGWRWKHUHDFWDQWVFDQEHDQH[WUHPHO\LPSRUWDQWIDFWRUDIIHFWLQJWKH UHDFWLRQNLQHWLFV7KHUHIRUHH[SHULPHQWVZHUHSHUIRUPHGSUHSDULQJUHDFWLYHPL[WXUHVZLWK HTXLPRODUDPRXQWVRIDFHWDOGHK\GHDQGJO\FHURODQG'062PRODUIUDFWLRQVUDQJLQJIURP WR7KHUHVXOWVDUHSUHVHQWHGLQ)LJXUH   )LJXUH       (IIHFWRIWKHVROYHQWPRODUIUDFWLRQRQWKHUHDFWLRQUDWH  7 . =   3 EDU =  LQLWLDODFHWDOGHK\GHJO\FHUROPRODUUDWLRVWLUULQJVSHHGRI USP   7KHUHDFWLRQSURFHHGHGDWORZHUUDWHVZKHQWKHVROYHQWDPRXQWZDVHQODUJHGGXHWRWKH GLOXWLRQ IDFWRU DSSOLHG WR WKH UHDFWLYH VSHFLHV )LJXUH  7KH REVHUYHG FKDQJHV LQ WKH Ϭй ϮϬй ϰϬй ϲϬй ϴϬй ϭϬϬй Ϭ ϭϬϬ ϮϬϬ ϯϬϬ ϰϬϬ ϱϬϬ ŽŶǀĞƌƐŝŽŶ dŝŵĞ;ŵŝŶͿ džƐŽůǀсϱϬйϬϯϬǁƚйĂƚ;džƉͿ džƐŽůǀсϱϬйϬϯϬǁƚйĂƚ;DŽĚĞůͿ džƐŽůǀсϳϱйϬϯϬǁƚйĂƚ;džƉͿ džƐŽůǀсϳϱйϬϯϬǁƚйĂƚ;DŽĚĞůͿ džƐŽůǀсϮϱйϬϭϱǁƚйĂƚ;džƉͿ džƐŽůǀсϮϱйϬϭϱǁƚйĂƚ;DŽĚĞůͿ džƐŽůǀсϱϬйϬϭϱǁƚйĂƚ;džƉͿ džƐŽůǀсϱϬйϬϭϱǁƚйĂƚ;DŽĚĞůͿ * /<&(52/$&(7$/6352'8&7,21%< 6 ,08/$7(' 0 29,1* % (' 5 ($&725     NLQHWLFV PLJKW DOVR EH UHODWHG ZLWK WKH KLQGHULQJ RI WKH DYDLODEOH DFWLYH VLWHV E\ '062 ZKLFKGXHWRLWVKLJKSRODULW\SUHVHQWVDKLJKDIILQLW\WRZDUGV$PEHU\VW  &RQFOXVLRQV $OWKRXJK VRPH VROYHQW VFUHHQLQJ PHWKRGRORJLHV KDYH EHHQ UHSRUWHG LQ WKH RSHQ OLWHUDWXUH QRQH ZDV VSHFLILFDOO\ RULHQWHG IRU LQWHJUDWHG UHDFWLYH²DGVRUSWLYH SURFHVVHV +HQFHLQWKLVFKDSWHUDSURPSWDQGFRQFLVHPHWKRGRORJ\ZDVGHYHORSHGIRUWKHVHOHFWLRQRI DVROYHQWIRUD60%5XQLWFRPSULVLQJWZRGLIIHUHQWVWDJHVILUVWDQH[WHQVLYHOLVWRIWKHPRVW FRPPRQO\ XVHG VROYHQWV LQ FKHPLFDO SURFHVVHV ZDV UHGXFHG WKURXJK WKH DSSOLFDWLRQ RI D UDWLQJSURFHGXUHEDVHGRQWKHLUSURSHUWLHVDQGWKHQH[SHULPHQWDOWHVWVZHUHSHUIRUPHGZLWK WKHVROYHQWVVHOHFWHGIURPWKHSUHYLRXVVFUHHQLQJVWHS :KHQ WKH PHWKRGRORJ\ GHYHORSHG ZDV DSSOLHG WR WKH V\QWKHVLV RI *($ WKURXJK WKH DFHWDOL]DWLRQUHDFWLRQEHWZHHQJO\FHURODQGDFHWDOGHK\GHFDWDO\VHGE\$PEHUO\VW'062 KDV GHPRQVWUDWHG WR EH WKH PRVW VXLWDEOH VROYHQW IRU WKLV UHDFWLRQ SUHVHQWLQJ WRS SHUIRUPDQFHV RQ DOPRVW HYHU\ WRSLF ,W SURYHG WR EH XQUHDFWLYH DQG PLVFLEOH ZLWK WKH UHDFWLRQ PHGLXP DQG PRVW LPSRUWDQWO\ LW SUHVHQWHG DQ DGVRUSWLRQ FDSDFLW\ WKDW FDQ SUHGLFWDEO\UHGXFHWKHVROYHQWFRQVXPSWLRQRQDIXWXUH60%5XQLW0RUHRYHULWVXVHKDVORZ KHDOWKDQGHQYLURQPHQWDOLPSDFW $GHWDLOHGNLQHWLFVWXG\RIWKHDFHWDOL]DWLRQUHDFWLRQLQWKHSUHVHQFHRI'062DOORZHGWKH GHVFULSWLRQ RI WKH UHDFWLRQ UDWH ODZ E\ D /++: PRGHO $ FRPSOHWH PDWKHPDWLFDO PRGHO LQFOXGLQJ PDVV WUDQVIHU UHVLVWDQFHV ZDV GHYHORSHG DQG SURYHG WR EH DEOH WR SUHGLFW WKH HIIHFWRQWKHUHDFWLRQUDWHSURPRWHGE\FKDQJHVLQWKHGHVLJQYDULDEOHVZLWKKLJKDFFXUDF\ SUHVHQWLQJ DFRUUHODWLRQFRHIILFLHQWRI)RU WKLVPRGHOD YDOXH RI  NPRO − ⋅ZDV HVWLPDWHGIRUWKHUHDFWLRQDFWLYDWLRQHQHUJ\:KHQFRPSDUHGZLWKWKHVROYHQWIUHHUHDFWLRQ WKH DGGLWLRQ RI '062 WR WKH V\VWHP DSSHDUV WR KDYH VRPH LPSDFW RQ WKH UHDFWLRQ SHUIRUPDQFHDVFRQVHTXHQFHRIWKHGLOXWLRQIDFWRUDQGWKHUHGXFWLRQRIDYDLODEOHFDWDO\VW DFWLYHVLWHVLPSRVHGE\LWVSUHVHQFH   1RWDWLRQ $EEUHYLDWLRQV '%( GLEXWKR[\HWKDQH 6 (/(&7,212)$ 6 2/9(17)25$1 , 17(*5$7(' 5 ($&7,9( ²$ '62537,9( 3 52&(66)257+( 6 <17+(6,62) *($    '(( GLHWKR[\HWKDQH '0( GLPHWKR[\HWKDQH '0) QQGLPHWK\OIRUPDPLGH '062 'LPHWK\O6XOIR[LGH *($ *O\FHURO(WK\O$FHWDO J35206 *HQHUDO3URFHVV0RGHOOLQJ6\VWHP /++: /DQJPXLU+LQVKHOZRRG+RXJHQ:DWVRQ 157/ 1RQ5DQGRP7ZR/LTXLG 60%5 6LPXODWHG0RYLQJ%HG5HDFWRU 81,)$& 8QLYHUVDO)XQFWLRQDO$FWLYLW\&RHIILFLHQW 81,48$& 8QLYHUVDO4XDVL&KHPLFDO    6\PEROV L & 0RODUFRQFHQWUDWLRQRIFRPSRXQGLLQWKHLQWUDSDUWLFOHIOXLG  PRO GP − ⋅  '  'LSROHPRPHQW    D ( 5HDFWLRQ$FWLYDWLRQ(QHUJ\  NPRO − ⋅  * ∆ 6WDQGDUGUHDFWLRQ*LEEVIUHHHQHUJ\  NPRO − ⋅  V ' + ∆ '062HQWKDOS\RIDGVRUSWLRQ  NPRO − ⋅  V : +∆ :DWHUHQWKDOS\RIDGVRUSWLRQ  NPRO − ⋅ HT . 5HDFWLRQ(TXLOLEULXPFRQVWDQW  F N 5HDFWLRQNLQHWLFFRQVWDQW    FDW GP PRO J PLQ − − ⋅ ⋅ ⋅   F N  $UUKHQLXVSUH  H[SRQHQWLDOIDFWRUIRUWKHUHDFWLRQNLQHWLF FRQVWDQW    FDW GP PRO J PLQ − − ⋅ ⋅ ⋅   V ' . '062DGVRUSWLRQHTXLOLEULXPFRQVWDQW   GP PRO − ⋅    V ' .  9DQ·W+RIISUH  H[SRQHQWLDOIDFWRUIRU'062DGVRUSWLRQ HTXLOLEULXPFRQVWDQW   GP PRO − ⋅   V : . :DWHUDGVRUSWLRQHTXLOLEULXPFRQVWDQW   GP PRO − ⋅    V : .  9DQ·W+RIISUH  H[SRQHQWLDOIDFWRUIRUZDWHUDGVRUSWLRQ HTXLOLEULXPFRQVWDQW   GP PRO − ⋅   /' 0HGLDQOHWKDOGRVH  PJ NJ − ⋅  1(  1XPEHURINLQHWLFH[SHULPHQWVSHUIRUPHG    * /<&(52/$&(7$/6352'8&7,21%< 6 ,08/$7(' 0 29,1* % (' 5 ($&725     ([SHULPHQWDO'HVFULSWLRQ &KHPLFDOV&DWDO\VWVDQG$GVRUEHQWV )RU WKH H[SHULPHQWV GHVFULEHG LQ WKLV &KDSWHU WKH IROORZLQJ FKHPLFDO FRPSRXQGV ZHUH DSSOLHG EOXH GH[WUDQ DFHWDOGHK\GH ! DQG JO\FHURO ! SXUFKDVHG IURP 6LJPD² $OGULFKGLPHWK\OVXOIR[LGH!IURP3URODERDQGZDWHUSXULILHGLQRXUODERUDWRULHV 7KH FKURPDWRJUDSKLF FROXPQ XVHG ZDV SDFNHG ZLWK $PEHUO\VW ZHW IURP 5RKP  +DDV 7KLV PDFURUHWLFXODU LRQ H[FKDQJH UHVLQ FRPSRVHG E\ D VW\UHQH GLYLQ\OEHQ]HQH SRO\PHULFPDWUL[IXQFWLRQDOL]HGZLWKVXOIRQLFJURXSV  62 + DFWVVLPXOWDQHRXVO\DVFDWDO\VW DQGDGVRUEHQWIRUWKHVWXGLHGV\VWHP7DEOHVXPPDUL]HVWKHPDLQSK\VLFDOSURSHUWLHVRI $PEHUO\VWZHWSURYLGHGE\WKHVXSSOLHUDQGUHSRUWHGLQWKHRSHQOLWHUDWXUH    7DEOH²$PEHUO\VWZHWSK\VLFDOSURSHUWLHV 3URSHUW\ 9DOXH $FLG6LWHV&RQFHQWUDWLRQ HT+ NJ +   6XUIDFHDUHD  P J   $YHUDJHSRUHGLDPHWHU QP   $YHUDJHSDUWLFOHGLDPHWHU P µ   3RURVLW\   ([SHULPHQWDO6HWXSDQG3URFHGXUH &KURPDWRJUDSKLF&ROXPQ&KDUDFWHUL]DWLRQ 7UDFHUH[SHULPHQWVZHUHFDUULHGRXWLQRUGHUWRDVVHVVWKHK\GURG\QDPLFVRIWKHIL[HG EHGXVHGIRUWKHGHWHUPLQDWLRQRIDGVRUSWLRQGDWDDQGIRUWKHV\QWKHVLVRI*($DGGUHVVHGLQ WKH SUHVHQW &KDSWHU 7KHVH H[SHULPHQWV FRQVLVWHG LQ WKH LQMHFWLRQ RI  / µ  SXOVHV RI D VROXWLRQRIEOXHGH[WUDQLQ'062DSSUR[LPDWHO\  J / − ⋅ LQWKHIL[HGEHGDQGUHFRUGLQJWKH RXWOHWFRQFHQWUDWLRQSURILOHXVLQJD899,6GHWHFWRU*LOVRQ0RGHO DW QP )LJXUH  SUHVHQWV D VFKHPH RI WKH H[SHULPHQWDO VHWXS XVHG ZKLFK FRPSULVHV D +LJK 3UHVVXUH /LTXLG &KURPDWRJUDSK\ +3/& SXPS *LOVRQ 0RGHO  D MDFNHWHG JODVV FROXPQ SDFNHG ZLWK $PEHUO\VW ZHW GHVFULEHG LQ 7DEOH  D WKHUPRVWDWLF EDWK /$8'$ /DXGD² 6 2537,21 ( 1+$1&(' 5 ($&7,9( 3 52&(66)257+( 6 <17+(6,62) *($  7 +( ) ,;(' % (' $ '62537,9( 5 ($&725     .|QLJVKRIHQ *HUPDQ\ DQG D GHWHFWRU SRVLWLRQHG DW WKH RXWOHW RI WKH DIRUHPHQWLRQHG FROXPQ   )LJXUH     ²  6FKHPHRIWKH  VHW  XS  XVHGIRUWUDFHUDQGEUHDNWKURXJKH[SHULPHQWV     7DEOH²)L[HGEHGFROXPQSURSHUWLHV 3URSHUW\ 9DOXH &DWDO\VW$GVRUEHQWZHLJKW J   &ROXPQOHQJWK FP   &ROXPQGLDPHWHU FP   %XONGHQVLW\ − ⋅J FP    7KH H[SHULPHQWV ZHUH SHUIRUPHG XQGHU LVRWKHUPDO FRQGLWLRQV  .  DQG IORZ UDWHV UDQJLQJIURP  PLQP/ − ⋅ WR  PLQP/ − ⋅   * /<&(52/$&(7$/6352'8&7,21%< 6 ,08/$7(' 0 29,1* % (' 5 ($&725     $GVRUSWLRQ(TXLOLEULXP,VRWKHUPV %LQDU\EUHDNWKURXJKH[SHULPHQWVZHUHSHUIRUPHGIRUWKHGHWHUPLQDWLRQRIWKHDGVRUSWLRQ HTXLOLEULXPLVRWKHUPVRIWKHVSHFLHVSUHVHQWLQWKH*($V\QWKHVLVDW . 7KHEUHDNWKURXJK FXUYHVZHUHREWDLQHGEDVHGRQDIURQWDODQDO\VLVWHFKQLTXHE\VHTXHQWLDOO\IHHGLQJVHYHUDO ELQDU\PL[WXUHVRINQRZQFRPSRVLWLRQRIDUHDFWDQWRUDSURGXFWRIWKHDFHWDOL]DWLRQUHDFWLRQ DQG '062 WR D IL[HG EHG DFFRUGLQJ WR WKH GHVFULEHG LQ 7DEOH  (DFK H[SHULPHQW SURFHHGHGXQWLOQRFKDQJHVZHUHREVHUYHGLQWKHRXWOHWVWUHDPFRPSRVLWLRQ  7DEOH²%LQDU\EUHDNWKURXJKH[SHULPHQWDOFRQGLWLRQV %LQDU\ 0L[WXUH ( (( ( ) )) ) 4 P/  PLQ − −− − ⋅ ⋅⋅ ⋅  &RPSRXQG   &RPSRXQG    ( (( ( ) )) ) & PRO GP   − −− − ⋅ ⋅⋅ ⋅  ( (( ( ) )) ) )HHG & PRO GP  − −− − ⋅ ⋅⋅ ⋅  ( (( ( ) )) ) & PRO GP   − −− − ⋅ ⋅⋅ ⋅  ( (( ( ) )) ) )HHG & PRO GP  − −− − ⋅ ⋅⋅ ⋅  *O\FHURO  '062                                     :DWHU  '062                                                                                                             *($  '062                                                                                           6 2537,21 ( 1+$1&(' 5 ($&7,9( 3 52&(66)257+( 6 <17+(6,62) *($  7 +( ) ,;(' % (' $ '62537,9( 5 ($&725      7KH VHWXS XVHG LQ WKHVH H[SHULPHQWV ZDV VLPLODU WR WKH SUHVHQWHG LQ )LJXUH  +RZHYHU LQVWHDG RI XVLQJ DQ RQOLQH 899,6 GHWHFWRU VDPSOHV ZHUH FROOHFWHG SHULRGLFDOO\ DQG DQDO\VHG LQ D JDV FKURPDWRJUDSK *&  3OXV 6KLPDG]X -DSDQ HTXLSSHG ZLWK D WKHUPDOFRQGXFWLYLW\GHWHFWRUDQGD&3:D[&%FROXPQ$JLOHQW7HFKQRORJLHV8QLWHG6WDWHV RI$PHULFDWKURXJKWKHDQDO\WLFDOPHWKRGGHVFULEHGLQ6HFWLRQ  *($6\QWKHVLVLQD)L[HG%HG$GVRUSWLYH5HDFWRU 7KH VWXG\ RI WKH SURGXFWLRQ RI *($ E\ D VRUSWLRQ HQKDQFHG UHDFWLYH SURFHVV ZDV SHUIRUPHGE\IHHGLQJWHUQDU\UHDFWLYHPL[WXUHVFRQWDLQLQJERWKDFHWDOL]DWLRQUHDFWDQWVDQG '062RUERWKSURGXFWVDQG'062WRDIL[HGEHGUHDFWRURSHUDWLQJLVRWKHUPDOO\DW  . DQG PRQLWRULQJ WKH RXWOHW FRQFHQWUDWLRQ KLVWRULHV WKURXJKRXW WKH H[SHULPHQWV 7KH IHHG FRPSRVLWLRQDQGIORZUDWHVDUHVXPPDUL]HGLQ7DEOH 7KH VHWXS DQG DQDO\WLFDO PHWKRG XVHG LQ WKHVH H[SHULPHQWV ZHUH WKH VDPH DV WKH UHSRUWHGLQ6HFWLRQVDQG  7DEOH²7HUQDU\EUHDNWKURXJKH[SHULPHQWDOFRQGLWLRQV 7HUQDU\ 0L[WXUH 4  ( (( ( ) )) ) P/  PLQ − −− − ⋅ ⋅⋅ ⋅  &RPSRXQG   &RPSRXQG   &RPSRXQG  &  ( (( ( ) )) ) PRO GP  − −− − ⋅ ⋅⋅ ⋅  )HHG & ( (( ( ) )) ) PRO GP  − −− − ⋅ ⋅⋅ ⋅   &  ( (( ( ) )) ) PRO GP  − −− − ⋅ ⋅⋅ ⋅  )HHG & ( (( ( ) )) ) PRO GP  − −− − ⋅ ⋅⋅ ⋅   &  ( (( ( ) )) ) PRO GP  − −− − ⋅ ⋅⋅ ⋅  )HHG & ( (( ( ) )) ) PRO GP  − −− − ⋅ ⋅⋅ ⋅  $FHWDOGHK\GH    *O\FHURO  '062                   :DWHU  *($  '062                                       7KH)L[HG%HG$GVRUSWLYH5HDFWRU 7KH H[SHULPHQWDO DQG PRGHO UHVXOWV REWDLQHG WKURXJKRXW WKH VWXG\ RI WKH DGVRUSWLRQ HTXLOLEULXPDQGWKHG\QDPLFIL[HGEHGRSHUDWLRQDUHUHSRUWHGZLWKLQWKLV6HFWLRQ  * /<&(52/$&(7$/6352'8&7,21%< 6 ,08/$7(' 0 29,1* % (' 5 ($&725     0DWKHPDWLFDO0RGHOOLQJDQG1XPHULFDO6ROXWLRQ ,QRUGHUWRSUHGLFWDEUHDNWKURXJKFXUYHRUDQLQWHUQDOFRQFHQWUDWLRQSURILOHRIDIL[HG EHGDGVRUSWLYHUHDFWRUWKURXJKDPDWKHPDWLFDOPRGHORQHPXVWKDYHLQWRDFFRXQWFRQYHFWLYH HIIHFWVWKHPDVVWUDQVIHUIURPWKHEXONSKDVHWRWKHVROLGSRUHVWKHDGVRUSWLRQNLQHWLFVDQG HTXLOLEULXP DQG WKH FKHPLFDO UHDFWLRQV RFFXUULQJ EHWZHHQ WKH SUHVHQW VSHFLHV 6HYHUDO PRGHOV KDYH EHHQ SURSRVHG WR GHVFULEH WKLV FKURPDWRJUDSKLF UHDFWRU    )RU WKH VWXGLHG V\VWHPWKHIROORZLQJDVVXPSWLRQVZHUHFRQVLGHUHG  ,VRWKHUPDORSHUDWLRQ  &RQVWDQWEHGOHQJWKDQGSDFNLQJSRURVLW\  3OXJIORZPRGHOZLWKD[LDOGLVSHUVLRQDQGQHJOLJLEOHUDGLDOGLVSHUVLRQ  9HORFLW\YDULDWLRQVUHVXOWLQJIURPEXONFRPSRVLWLRQFKDQJHV  0DVVWUDQVIHUGHVFULEHGE\WKHOLQHDUGULYLQJIRUFHPRGHO  &KHPLFDOUHDFWLRQRFFXUULQJH[FOXVLYHO\DWWKHFDWDO\VWDFWLYHVLWHV  7KH PDVV WUDQVIHU PHFKDQLVP DGRSWHG LQ WKLV PRGHO IRUFHV WKH GLVWLQFWLRQ RI WKH EXON PRELOHSKDVHIURPWKHVWDJQDQWIOXLGSKDVHLQVLGHWKHDGVRUEHQWSDUWLFOHSRUHVDQGWKHVROLG SKDVHZKHUHWKHFRPSRXQGVDGVRUEDVUHSUHVHQWHGLQ)LJXUH    )LJXUH     ²  6FKHPHRIWKHIL[HGEHGFROXPQ  D  DQGWKHPDVVWUDQVIHUPHFKDQLVPEHWZHHQ WKHEXONIOXLGDQGWKHFDWDO\VWDGVRUEHQWSDUWLFOHVE  &RQVHTXHQWO\ VHSDUDWH EXON DQG SDUWLFOH PDVV EDODQFH HTXDWLRQV PXVW EH ZULWWHQ DV VKRZQLQHTXDWLRQVWR  6 2537,21 ( 1+$1&(' 5 ($&7,9( 3 52&(66)257+( 6 <17+(6,62) *($  7 +( ) ,;(' % (' $ '62537,9( 5 ($&725     ( ) ( ) 2 , , , , , , 2 16 ε ε ∂ ∂ ∂ − + + − = ∂ ∂ ∂ b i b i b i b LDF i b i p i ax b p uC C C k C C D t z d z   ( ) , , 1= + − PT i p p i p i C C q ε ε  ( ) ( ) , , , , , 6 1 ∂ = − + ℜ ∂ − PT i b LDF i b i p i i p i p b Ck C C C t d ρ νε   ZKHUH  E L & DQG  37 L & UHSUHVHQWWKHEXONDQGSDUWLFOHFRQFHQWUDWLRQVRIFRPSRXQG L ZLWK WKH ODWWHU EHLQJ UHODWHG WR WKH DYHUDJH SRUH DQG DGVRUEHG FRQFHQWUDWLRQV  S L &  DQG L T  UHVSHFWLYHO\ W LVWLPH ] LVWKHD[LDOFRRUGLQDWH X LVWKHLQWHUVWLWLDOIOXLGYHORFLW\ D[ ' LV WKHD[LDOGLVSHUVLRQFRHIILFLHQW  /') L N LVWKHJOREDOPDVVWUDQVIHUFRHIILFLHQWRIFRPSRXQG L  E ε  DQG S ε  DUH WKH EHG DQG SDUWLFOH SRURVLW\ E ρ  LV WKH EXON GHQVLW\ S G  LV WKH SDUWLFOH GLDPHWHU L ν  LV WKH VWRLFKLRPHWULF FRHIILFLHQW RI FRPSRXQG L  DQG ℜ  LV WKH UHDFWLRQ UDWH GHVFULEHG LQ WHUPV RI FRQFHQWUDWLRQV E\ WKH /DQJPXLU+LQVKHOZRRG+RXJHQ:DWVRQ /++: ODZHTXDWLRQDFFRUGLQJWRWKHNLQHWLFVWXG\SUHVHQWHGLQ6HFWLRQ )RU WKH UHVROXWLRQ RI WKLV V\VWHP RI SDUWLDO GLIIHUHQWLDO HTXDWLRQV DQ LQLWLDO FRQGLWLRQ FRUUHVSRQGLQJWRWKHVDWXUDWLRQRIWKHIL[HGEHGSULRUWRWKHH[SHULPHQWVDQGWZRERXQGDU\ FRQGLWLRQV IRUPXODWHG E\ 'DQFNZHUWV IRU WKH LQOHW DQG RXWOHW RI WXEXODU UHDFWRUV   ZHUH GHILQHGDFFRUGLQJWRHTXDWLRQVWR   0 , , , 0,= ∀ → = = b i p i b i t z C C C    , , , 0 0 0, = = ∂ = ∀ → = − ∂ b i in i b i ax z z C z t uC u C D z   , , 0 b i z L C z L t z = ∂ = ∀ → = ∂   $VWKHEXONFRQFHQWUDWLRQLVFRQWLQXRXVO\FKDQJLQJWKURXJKRXWDFKURPDWRJUDSKLFSURFHVV WKHIOXLGLQWHUVWLWLDOYHORFLW\LVH[SHFWHGWRXQGHUJRVOLJKWIOXFWXDWLRQVGXHWRWKHGLIIHUHQW PRODUYROXPHV  0 L 9 RIWKHVSHFLHVLQYROYHG7KHVHYDULDWLRQVZHUHDFFRXQWHGIRUEDVHGRQ WKHWRWDOPDVVEDODQFHDQGDUHH[SUHVVHGE\HTXDWLRQDQGWKHFRUUHVSRQGLQJERXQGDU\ FRQGLWLRQHTXDWLRQ  * /<&(52/$&(7$/6352'8&7,21%< 6 ,08/$7(' 0 29,1* % (' 5 ($&725     ( ) , , , , 1 16 = − ∂= − − ∂ ¦ NC b LDF i M i b i p i i b p uk V C C z d ε ε   0 0, = = ∀ → = z z t u u   7KH GHWHUPLQDWLRQ RI WKH JOREDO PDVV WUDQVIHU FRHIILFLHQW  /') L N  DV D IXQFWLRQ RI WKH LQWHUQDODQGH[WHUQDOPDVV WUDQVIHUFRHIILFLHQWV  LQW L N DQG  H[W L N UHVSHFWLYHO\ZDVFDUULHG RXWE\HVWDEOLVKLQJDQDQDORJ\WRWKHDVVRFLDWLRQRIUHVLVWRUVLQVHULHVLQHOHFWULFDOV\VWHPV HTXDWLRQDVFRPPRQO\UHSRUWHGLQWKHRSHQOLWHUDWXUH    , t, int, 1 1 1 ε = + LDF i ex i p i k k k    1RGLUHFWPHDVXUHRIWKHPDVVWUDQVIHUFRHIILFLHQWVZDVSHUIRUPHGLQWKLVZRUN,QVWHDG WKHLUYDOXHVZHUHHVWLPDWHGEDVHGRQFRUUHODWLRQV7KHLQWHUQDOPDVVWUDQVIHUFRHIILFLHQWZDV FRPSXWHGDFFRUGLQJWRHTXDWLRQ    , , 10 = eff i int i p D kd    ZKHUH  HII L '  LV WKH HIIHFWLYH GLIIXVLRQ FRHIILFLHQW RI FRPSRXQG L  LQ D PXOWLFRPSRQHQW PL[WXUH GHWHUPLQHG E\ DSSO\LQJ WKH 3HUNLQV DQG *HDQNRSOLV   PL[LQJ UXOH WR WKH LQILQLWH GLOXWLRQGLIIXVLRQFRHIILFLHQWVHVWLPDWHGE\WKH6FKHLEHO  HTXDWLRQDQGDVVXPLQJDSDUWLFOH WRUWXRVLW\ YDOXH HTXDO WR WKH LQYHUVH RI WKH SDUWLFOH SRURVLW\ DV UHSRUWHG E\ :DNDR DQG 6PLWK  VHH$SSHQGL[IRUPRUHGHWDLOV 7KH H[WHUQDO PDVV WUDQVIHU FRHIILFLHQW ZDV SUHGLFWHG E\ WKH :LOVRQ DQG *HDQNRSOLV FRUUHODWLRQ  GHVFULEHGE\HTXDWLRQ  ( ) 0.33 1.09 p p b Sh Re Sc ε =    7KH6KHUZRRG5H\QROGVHYDOXDWHGDWWKHSDUWLFOHFRQGLWLRQVDQG6FKPLGWGLPHQVLRQOHVV QXPEHUV S 6K  S 5H DQG 6F DUHGHILQHGE\HTXDWLRQVDQGFRUUHVSRQGLQJO\  6 2537,21 ( 1+$1&(' 5 ($&7,9( 3 52&(66)257+( 6 <17+(6,62) *($  7 +( ) ,;(' % (' $ '62537,9( 5 ($&725     , , = ext i p p i m k d Sh D   = ρ µ p p ud Re  , i m Sc D µ ρ =   ,WPXVWEHPHQWLRQHGWKDWWKHDSSOLFDWLRQRIWKLVFRUUHODWLRQLVOLPLWHGWRV\VWHPVZKHUH WKHSDUWLFOH5H\QROGVQXPEHUUDQJHVIURPWR 7RFRPSOHWHWKHIL[HGEHGUHDFWRUPRGHODGHVFULSWLRQRIWKHDGVRUSWLRQHTXLOLEULXPZDV UHTXLUHG 3UHYLRXV DXWKRUV KDYH DWWHPSWHG WR H[SODLQ WKH VRUSWLRQ SKHQRPHQD LQ LRQ H[FKDQJH SRO\PHULF UHVLQV PDNLQJ XVHRI PRGHOVWKDW DFFRXQWIRU LWV VZHOOLQJ DQGSRO\PHU SKDVHDFWLYLWLHVVXFKDVWKHPRGLILHG)ORU\+XJJLQVPRGHO  +RZHYHUPRUHUHFHQWVWXGLHV GHPRQVWUDWHG WKDW WKLV PRGHO LV QRW DEOH WR SUHGLFW WKH PXOWLFRPSRQHQW DGVRUSWLRQ HTXLOLEULXP RYHU UHVLQV ZLWK KLJK FURVVOLQN GHJUHHV WKDW FRQWDLQ KLJKO\ SRODU IXQFWLRQDO JURXSV   7KH/DQJPXLUPRGHOKDVEHHQLQGLFDWHGDVDQLQWHUHVWLQJDOWHUQDWLYHIRUWKH GHVFULSWLRQ RI WKH DGVRUSWLRQ HTXLOLEULXP IRU UHDFWLYHDGVRUSWLYH SURFHVVHV FRPSULVLQJ DFHWDOL]DWLRQUHDFWLRQV  7KHPRGHOLVHDV\WRDSSO\QRWUHTXLULQJH[WHQVLYHFRPSXWDWLRQ DQG LW ZDV DEOH WR SUHGLFW ZLWK VLJQLILFDQW DFFXUDF\ WKH H[SHULPHQWDO DGVRUSWLRQ GDWD UHSRUWHG 7KH/DQJPXLUPRGHOLVEDVHGRQIRXUVWDWHPHQWV  0ROHFXOHVDGVRUEDWORFDOL]HGDFWLYHVLWHV  (DFKVLWHFDQKROGRQO\RQHDGVRUEDWHPROHFXOHIRUPLQJDPRQROD\HUDWWKHDGVRUEHQW VXUIDFH  $OOVLWHVDUHHQHUJHWLFDOO\HTXLYDOHQW  $GVRUEHGPROHFXOHVGRQRWLQWHUDFWZLWKPROHFXOHVDGVRUEHGRQVXUURXQGLQJVLWHV  $VLPSOHNLQHWLFGHULYDWLRQRIWKLVPRGHODOORZVWKHGHWHUPLQDWLRQRIWKHPDWKHPDWLFDO H[SUHVVLRQWKDWGHVFULEHVWKHDGVRUSWLRQHTXLOLEULXPLVRWKHUPIRUDPXOWLFRPSRQHQWV\VWHP 7KLVH[SUHVVLRQLVSUHVHQWHGLQHTXDWLRQ  max,i , , 1 = + ¦ i p i iNC j p i j Q K C q K C    * /<&(52/$&(7$/6352'8&7,21%< 6 ,08/$7(' 0 29,1* % (' 5 ($&725     ZKHUH  PD[ L 4 LVWKHPRQROD\HUFDSDFLW\DQG L . LVWKHDGVRUSWLRQHTXLOLEULXPFRQVWDQWIRU FRPSRXQG L  $OWKRXJK WKH UHVXOWV SURYLGHG E\ WKH PRGHO DUH LQ JRRG DJUHHPHQW ZLWK WKH H[SHULPHQWDO GDWD SXEOLVKHG LW LV NQRZQ WKDW WKH /DQJPXLU HTXLOLEULXP PRGHO LV QRW D UHOLDEOH GHVFULSWLRQ RI WKH SK\VLFDO SKHQRPHQD EHKLQG DGVRUSWLRQ LQ LRQ H[FKDQJH UHVLQV QDPHO\ UHJDUGLQJ WKH PRQROD\HU DGVRUSWLRQ DVVXPSWLRQ )RU WKLV DVVXPSWLRQ WR EH FRUURERUDWHG WKH PD[LPXP PRODU FDSDFLW\ RI D FHUWDLQ DGVRUEHQW VKRXOG EH WKH VDPH IRU HYHU\ VSHFLHV ZKLFK LV QRW YHULILHG ZKHQ WKLV YDOXH LV PHDVXUHG IRU PROHFXOHV RI ZLGHO\ GLIIHUHQWVL]HV+RZHYHUVWXGLHVKDYHEHHQSUHVHQWHGZHUHDFRQVWDQWPRQROD\HUFDSDFLW\ KDVEHHQDVVXPHGLQWHUPVRIPDVV  RUYROXPH  IRUDOOVSHFLHVLQVWHDGRIPRODUDPRXQW 7KH GHYHORSHG PDWKHPDWLFDO PRGHO ZDV LPSOHPHQWHG LQ J35206 *HQHUDO 3URFHVV 0RGHOOLQJ6\VWHPYHUVLRQ7KHD[LDOGLPHQVLRQZDVGLVFUHWL]HGLQILQLWHHOHPHQWVD WKLUGRUGHURUWKRJRQDOFROORFDWLRQPHWKRG2&)(0ZDVDSSOLHGDQGWKHV\VWHPRIHTXDWLRQV ZDVVROYHGXVLQJWKH'$62/9LQWHJUDWHGVROYHU  &KURPDWRJUDSKLF&ROXPQ&KDUDFWHUL]DWLRQ ,QRUGHUWRHVWLPDWHWKHIL[HGEHGSRURVLW\DQGWKH3HFOHWQXPEHU 3H ZKLFKUHODWHVWKH FRQYHFWLYH DQG D[LDO GLVSHUVLRQ HIIHFWV WKURXJK HTXDWLRQ  WUDFHU H[SHULPHQWV ZHUH SHUIRUPHG LQ D EHG RI VSKHULFDO $PEHUO\VW SDUWLFOHV VDWXUDWHG ZLWK '062 DQG RSHUDWHG LVRWKHUPDOO\DW  .   ax uL Pe D =    7KHFROXPQUHVSRQVHWRDQLQMHFWLRQRID   NJ P − ⋅VROXWLRQRIEOXHGH[WUDQLQ'062DW GLIIHUHQWIORZUDWHVZDVPRQLWRUHGXVLQJD899,6GHWHFWRU'XHWRWKHGLOXWLRQLPSRVHGWR WKH WUDFHU VSHFLHV LW ZDV UHDVRQDEOH WR DVVXPH D SURSRUWLRQDO UHODWLRQ EHWZHHQ LWV FRQFHQWUDWLRQDQGWKHGHWHFWRUVLJQDO 7KHEOXHGH[WUDQKLJKPROHFXODUVL]HSUHFOXGHVLWVSHQHWUDWLRQLQ$PEHUO\VWSDUWLFOH SRUHV7KHUHIRUHWKHEHGSRURVLW\FRXOGEHFRPSXWHGWKURXJKWKHUDWLREHWZHHQWKHVSDFH WLPH τ DQGWKHPHDQUHVLGHQFHWLPH U W GHWHUPLQHGIURPWKHILUVWVWDWLVWLFDOPRPHQWRI WKH UHVLGHQFH WLPH GLVWULEXWLRQ FXUYHV HTXDWLRQ  7KH 3HFOHW QXPEHU RQ WKH RWKHU KDQGZDVHVWLPDWHGEDVHGRQWKHYDULDQFHRIWKHH[SHULPHQWDOUHVLGHQFHWLPHGLVWULEXWLRQ FXUYHVGHWHUPLQHGE\LWVVHFRQGVWDWLVWLFDOPRPHQWHTXDWLRQ7DEOHSUHVHQWVWKH IL[HG EHG FKDUDFWHULVWLFV H[SHULPHQWDOO\ GHWHUPLQHG E\ WKH WUDFHU H[SHULPHQWV E\ WKH PRPHQWVPHWKRG   6 2537,21 ( 1+$1&(' 5 ($&7,9( 3 52&(66)257+( 6 <17+(6,62) *($  7 +( ) ,;(' % (' $ '62537,9( 5 ($&725     ( ) ( ) ( ) 0 ∞ = ³ out out C t E t C t dt   ( ) 0 r b FB tE t dt t V Q ετ ∞ = = ³  ( ) ( ) 2 2 22 0 2 2 r r tr t t Pe t t E t dt σ ∞ = = − ³   7KHYDULDEOHV ( ) ( W  )% 9 DQG 4 UHSUHVHQWWKHUHVLGHQFHWLPHGLVWULEXWLRQWKHIL[HGEHG UHDFWRUYROXPHDQGWKHIHHGIORZUDWHUHVSHFWLYHO\  7DEOH7UDFHUH[SHULPHQWVUHVXOWV ( (( ( ) )) ) 4 P/  PLQ − −− − ⋅ ⋅⋅ ⋅  ( (( ( ) )) ) U W PLQ  E ε εε ε   W σ σσ σ  3H                       $VUHDFWLRQDGVRUSWLRQDQGPDVVWUDQVIHUPHFKDQLVPVEHWZHHQWKHEXONDQGWKHSDUWLFOH DUH DEVHQW LQ WUDFHU H[SHULPHQWV WKH IL[HG EHG PRGHO SUHVHQWHG LQ 6HFWLRQ  FDQ EH UHGXFHGWRDVLPSOHGLVSHUVLYHIORZPDVVEDODQFHHTXDWLRQDQGWKHUHVSHFWLYHLQLWLDO DQGERXQGDU\FRQGLWLRQVHTXDWLRQVWR  2 , , , 2 ∂ ∂ ∂ + = ∂ ∂ ∂ b i b i b i ax C C C u D t z z    )LJXUHVKRZVWKHH[SHULPHQWDODQGVLPXODWHGUHVLGHQFHWLPHGLVWULEXWLRQFXUYHV  * /<&(52/$&(7$/6352'8&7,21%< 6 ,08/$7(' 0 29,1* % (' 5 ($&725        )LJXUH       ([SHULPHQWDODQGSUHGLFWHGEUHDNWKURXJKFXUYHVIRUWKHELQDU\ *($  '062DW  . DQGIORZUDWHVRIDSSUR[LPDWHO\   P/ PLQ − ⋅ DDQG   P/ PLQ − ⋅ E   7KH GLUHFW REVHUYDWLRQ RI WKH SUHYLRXV ILJXUHV LQGLFDWHV WKDW WKH PRGHO LV LQ JRRG DJUHHPHQW ZLWK WKH H[SHULPHQWV 1HYHUWKHOHVV WKH TXDOLW\ RI WKH SUHVHQWHG ILWWLQJV ZDV TXDQWLILHGE\FRPSXWLQJLWVFRUUHODWLRQFRHIILFLHQW  &RUUHO 5 DFFRUGLQJWRHTXDWLRQ ϬϬ ϯϱ ϳϬ ϭϬϱ ϭϰϬ ϬϬ Ϯϱ ϱϬ ϳϱ ϭϬϬ Ϭ ϯϱ ϳϬ ϭϬϱ ϭϰϬ ϭϳϱ ϮϭϬ D^K ;ŵŽůͼ>ͲϭͿ ' ;ŵŽůͼ>ͲϭͿ dŝŵĞ;ŵŝŶͿ ';džƉͿ ';DŽĚĞůͿ D^K;džƉͿ D^K;DŽĚĞůͿ ĂͿ ϬϬ ϯϱ ϳϬ ϭϬϱ ϭϰϬ ϬϬ Ϯϱ ϱϬ ϳϱ ϭϬϬ Ϭ ϭϬϬ ϮϬϬ ϯϬϬ ϰϬϬ ϱϬϬ D^K ;ŵŽůͼ>ͲϭͿ ' ;ŵŽůͼ>ͲϭͿ dŝŵĞ;ŵŝŶͿ ';džƉͿ ';DŽĚĞůͿ D^K;džƉͿ D^K;DŽĚĞůͿ ďͿ 6 2537,21 ( 1+$1&(' 5 ($&7,9( 3 52&(66)257+( 6 <17+(6,62) *($  7 +( ) ,;(' % (' $ '62537,9( 5 ($&725      ( ) () 2 exp mod , , , , , , 1 1 1 2 2 mod exp , , , , 1 1 1 1 = = = = = = − = − − ¦¦¦ ¦¦¦ NC NE NP out i j k out i j k i j k Correl NC NE NP out i j k out i i j k C C R C C    ZKHUH 1&  1(  DQG 13  DUH WKH QXPEHU RI FRPSRXQGV H[SHULPHQWV DQG GDWD SRLQWV UHVSHFWLYHO\7KHKLJKYDOXHREWDLQHGIRUWKLVSDUDPHWHU  DOORZHGWRFRQILUPWKDWWKH PDWKHPDWLFDOPRGHOLPSOHPHQWHGZDVLQIDFWDEOHWRDFFXUDWHO\GHVFULEHWKHEUHDNWKURXJK FXUYHVIRUDOOVSHFLHVFRQVLGHULQJWKHHVWLPDWHGDGVRUSWLRQSDUDPHWHUV  *($6\QWKHVLVLQD)L[HG%HG$GVRUSWLYH5HDFWRU 7KH V\QWKHVLV RI *($ LQ D IL[HG EHG DGVRUSWLYH UHDFWRU ZDV DFKLHYHG E\ IHHGLQJ DQ HTXLPRODUPL[WXUHFRQWDLQLQJDFHWDOGHK\GHJO\FHURODQG'062WRDIL[HGEHGSDFNHGZLWK $PEHUO\VW SUHYLRXVO\ VDWXUDWHG ZLWK '062 DW D IORZUDWH RI   − ⋅ P/ PLQ 7KH WHPSHUDWXUHZDVNHSWDW  . DQGWKHHTXLSPHQWZDVRSHUDWHGDWDWPRVSKHULFSUHVVXUH $IWHU UHDFKLQJ WKH VWHDG\ VWDWH DSSUR[LPDWHO\  PLQ  DIWHU WKH EHJLQQLQJ RI WKH H[SHULPHQWWKHUHDFWLRQPHGLDZDVHOXWHGIURPWKHUHDFWRUE\IHHGLQJDSXUH'062VWUHDP DW   − ⋅ P/ PLQ  7KH H[SHULPHQWDO UHVXOWV DUH SUHVHQWHG LQ )LJXUH  WRJHWKHU ZLWK WKH VLPXODWLRQV REWDLQHG WKURXJK WKH PDWKHPDWLFDO PRGHO GHYHORSHG LQ 6HFWLRQ  DQG WKH DGVRUSWLRQ DQG UHDFWLRQ GDWD SUHYLRXVO\ FROOHFWHG +RZHYHU RQH PXVW PHQWLRQ WKDW WKH DFHWDOGHK\GH DGVRUSWLRQ LVRWKHUP ZDV LPSRVVLEOH WR EH GHWHUPLQHG VLQFH WKLV FRPSRXQG XQGHUJRHVROLJRPHUL]DWLRQUHDFWLRQVZKHQLQFRQWDFWZLWKDFLGV  ,QVWHDGWKHDGVRUSWLRQ SDUDPHWHUV IRU WKLV FRPSRXQG ZHUH DVVXPHG WR EH HTXDO WR WKRVH REWDLQHG IRU JO\FHURO EDVHGRQ WKHVLPLODULW\ RIWKH EUHDNWKURXJK FXUYHV RI WKHWZRFRPSRXQGVLQ WKH IL[HG EHG DGVRUSWLYHUHDFWRU  * /<&(52/$&(7$/6352'8&7,21%< 6 ,08/$7(' 0 29,1* % (' 5 ($&725       )LJXUH     ²  6\QWKHVLVRI*($LQ  DIL[HGEHGDGVRUSWLYHUHDFWRU  DW  .  E\IHHGLQJ D  VROXWLRQFRQWDLQLQJ   − ⋅ PRO / RIDFHWDOGHK\GH   − ⋅ PRO / RIJO\FHURODQG   − ⋅ PRO / RI'062DW   − ⋅ P/ PLQ DDQGUHJHQHUDWLRQRIWKHEHGZLWKSXUH'062DW   − ⋅ P/ PLQ E  ϬϬ ϯϱ ϳϬ ϭϬϱ ϭϰϬ ϬϬ ϱϬ ϭϬϬ ϭϱϬ ϮϬϬ ϮϱϬ ϯϬϬ ;ŵŽůͼ>ͲϭͿ dŝŵĞ;ŵŝŶͿ ';džƉͿ ';DŽĚĞůͿ tĂƚĞƌ;džƉͿ tĂƚĞƌ;DŽĚĞůͿ 'ůLJĐĞƌŽů;džƉͿ 'ůLJĐĞƌŽů;DŽĚĞůͿ ĐĞƚĂůĚĞŚLJĚĞ;džƉͿ ĐĞƚĂůĚĞŚLJĚĞ;DŽĚĞůͿ D^K;džƉͿ D^K;DŽĚĞůͿ ĂͿ ϬϬ ϯϱ ϳϬ ϭϬϱ ϭϰϬ ϬϬ ϱϬ ϭϬϬ ϭϱϬ ϮϬϬ ;ŵŽůͼ> Ͳϭ Ϳ dŝŵĞ;ŵŝŶͿ ';džƉͿ ';DŽĚĞůͿ tĂƚĞƌ;džƉͿ tĂƚĞƌ;DŽĚĞůͿ 'ůLJĐĞƌŽů;džƉͿ 'ůLJĐĞƌŽů;DŽĚĞůͿ ĐĞƚĂůĚĞŚLJĚĞ;džƉͿ ĐĞƚĂůĚĞŚLJĚĞ;DŽĚĞůͿ D^K;džƉͿ D^K;DŽĚĞůͿ ďͿ 6 2537,21 ( 1+$1&(' 5 ($&7,9( 3 52&(66)257+( 6 <17+(6,62) *($  7 +( ) ,;(' % (' $ '62537,9( 5 ($&725     )LJXUHDVKRZVWKDWJO\FHURODQGDFHWDOGHK\GHZHUHWKHILUVWVSHFLHVWRHOXWHIURP WKH IL[HG EHG UHDFWRU DIWHU DSSUR[LPDWHO\  PLQ  7KH FRQWLQXHG FRQWDFW EHWZHHQ WKH UHDFWDQWVDQGWKHDFLGLRQH[FKDQJHUHVLQFDWDO\VWSURPRWHGWKHIRUPDWLRQRIZDWHUDQG*($ DFKLHYLQJ FRQFHQWUDWLRQV DERYH   − ⋅ PRO /  DW WKH VWHDG\ VWDWH   PLQ  7KH HOXWLRQ RI *($ EHIRUH ZDWHU FRXOG EH DQWLFLSDWHG E\ WKH DGVRUSWLRQ HTXLOLEULXP UHVXOWV IRUPHUO\ REWDLQHG 7KH UHDFWLRQ VWRLFKLRPHWU\ ZRXOG LPSO\ WKDW ZKHQ DQ HTXLPRODU PL[WXUH RI DFHWDOGHK\GHDQGJO\FHUROLVIHGWRDIL[HGEHGDGVRUSWLYHUHDFWRUWKHRXWOHWFRQFHQWUDWLRQRI ERWKUHDFWDQWVDQGERWKSURGXFWVDWWKHVWHDG\VWDWHVKRXOGEHWKHVDPH7KLVEHKDYLRXUZDV QRW REVHUYHG IRU WKH H[SHULPHQW SUHVHQWHG LQ )LJXUH  D VLQFH WKH IHHG VROXWLRQ FRQWDLQHG XQHYHQ DPRXQWV RI WKH UHDFWDQWV DQG D VOLJKW FRQWDPLQDWLRQ ZLWK ZDWHU 1HYHUWKHOHVV WKHVH IDFWV ZHUH WDNHQ LQWR DFFRXQW LQ WKH FRPSXWDWLRQ RI WKH VLPXODWHG UHVXOWV7KHUHJHQHUDWLRQVWHSSUHVHQWHGLQ)LJXUHEZDVSHUIRUPHGVXEVHTXHQWO\WR WKH UHDFWLRQ VWHS ZLWK WKH HOXWLRQ RI DOO WKH FRPSRXQGV IROORZLQJ WKH VDPH RUGHU DV WKH UHSRUWHGIRUWKHSUHFHGLQJH[SHULPHQW $GGLWLRQDOO\)LJXUHGHPRQVWUDWHVWKDWWKHPRGHOZDVDEOHWRHVWLPDWHWKHHYROXWLRQ RIWKHRXWOHWVWUHDPFRQFHQWUDWLRQRIHDFKFRPSRXQGZLWKWLPH$FRUUHODWLRQFRHIILFLHQWRI ZDVGHWHUPLQHGIRUWKHILWWLQJRIWKHH[SHULPHQWDOGDWDDFFRUGLQJWRHTXDWLRQ )RUDEHWWHUXQGHUVWDQGLQJRIWKHG\QDPLFEHKDYLRXURIWKHIL[HGEHGUHDFWRUWKHLQWHUQDO FRQFHQWUDWLRQSURILOHVDORQJWKHQRUPDOL]HGD[LDOFRRUGLQDWHDUHSUHVHQWHGLQ)LJXUHIRU VHYHUDOLQVWDQWVGXULQJWKHUHDFWLRQVWHS  * /<&(52/$&(7$/6352'8&7,21%< 6 ,08/$7(' 0 29,1* % (' 5 ($&725              )LJXUH²,QWHUQDOFRQFHQWUDWLRQSURILOHVRIWKHIL[HGEHGDGVRUSWLYHUHDFWRU  PLQ D  P LQ E  PLQ F DQG  PLQ GDIWHUWKHEHJLQQLQJRIWKHV\QWKHVLVRI*($E\IHHGLQJDVROXWLRQFRQWDLQLQJ   − ⋅ PRO / RI DFHWDOGHK\GH   − ⋅ PRO / RIJO\FHURODQG   − ⋅ PRO / RI'062DW   − ⋅ P/ PLQ   = 7 .   :KHQWKHPL[WXUHFRQWDLQLQJDFHWDOGHK\GHJO\FHURODQG'062LVLQWURGXFHGLQWKHIL[HG EHGDGVRUSWLYHUHDFWRUERWKUHDFWDQWVGLIIXVHWKURXJKUHVLQSRUHVDQGDGVRUEDWLWVDFWLYH VLWHVGLVSODFLQJ'062DVVKRZQLQ)LJXUHD7KHDFHWDOL]DWLRQUHDFWLRQWDNHVSODFHLQ WKH VROLG SKDVH DQG DGVRUEHG *($ DQG ZDWHU DUH IRUPHG DFFRUGLQJ WR WKH UHDFWLRQ VWRLFKLRPHWU\ 'XH WR LWV ORZHU DIILQLW\ WRZDUGV WKH DFLG VXOIRQLF JURXSV RI WKH UHVLQ *($ HOXWHV EHIRUH ZDWHU DSSUR[LPDWHO\ DW  PLQ  DQG  PLQ  UHVSHFWLYHO\ $Q LQWHUQDO FRQFHQWUDWLRQ SURILOH LQ DQ LQVWDQW FRPSULVHG EHWZHHQ *($ DQG ZDWHU HOXWLRQ WLPHV LV SUHVHQWHGLQ)LJXUHE,WLVSRVVLEOHWRREVHUYHIURP)LJXUHFWKDWWKHVHFWLRQRI WKHIL[HGEHGUHDFWRUFORVHUWRLWVLQOHWZKHUHUHDFWLRQRFFXUVDWWKHKLJKHVWUDWHUHDFKHV WKHVWHDG\VWDWHLQDOPRVW  PLQ KRZHYHUWKHSURSDJDWLRQRIWKHUHDFWLYHIURQWDORQJWKH D[LDO GLPHQVLRQ RI WKH UHDFWRU DQG WKH VLPXOWDQHRXV VHOHFWLYH DGVRUSWLRQ RI WKH SURGXFWV SUHVHUYHV WKH GULYLQJ IRUFH RI WKH FKHPLFDO UHDFWLRQ IRU D ORQJHU SHULRG RI WLPH 7KH FRQFHQWUDWLRQSURILOHVHYROXWLRQSURFHHGVXQWLOWKHUHVLQLVFRPSOHWHO\VDWXUDWHGZLWKZDWHU ϬϬ ϯϱ ϳϬ ϭϬϱ ϭϰϬ ϬϬ ϬϮ Ϭϰ Ϭϲ Ϭϴ ϭϬ ;ŵŽůͼ>ͲϭͿ nj> ĂͿ ϬϬ ϯϱ ϳϬ ϭϬϱ ϭϰϬ ϬϬ ϬϮ Ϭϰ Ϭϲ Ϭϴ ϭϬ ;ŵŽůͼ>ͲϭͿ nj> ďͿ ϬϬ ϯϱ ϳϬ ϭϬϱ ϭϰϬ ϬϬ ϬϮ Ϭϰ Ϭϲ Ϭϴ ϭϬ ;ŵŽůͼ> Ͳϭ Ϳ nj> ĐͿ ϬϬ ϯϱ ϳϬ ϭϬϱ ϭϰϬ ϬϬ ϬϮ Ϭϰ Ϭϲ Ϭϴ ϭϬ ;ŵŽůͼ> Ͳϭ Ϳ nj> ĚͿ 'ůLJĐĞƌŽů ĐĞƚĂůĚĞŚLJĚĞ tĂƚĞƌ ' D^K 6 2537,21 ( 1+$1&(' 5 ($&7,9( 3 52&(66)257+( 6 <17+(6,62) *($  7 +( ) ,;(' % (' $ '62537,9( 5 ($&725     $IWHU WKLV PRPHQW WKH VHSDUDWLRQ EHWZHHQ *($ DQG ZDWHU EHFRPHV LPSRVVLEOH WKH RXWOHW VWUHDPFRPSRVLWLRQUHPDLQVFRQVWDQWDQGWKHUHDFWRUUHDFKHVLWVILQDOVWHDG\VWDWHREVHUYHG LQ)LJXUHG )RU WKH RSHUDWLQJ FRQGLWLRQV VHW LQ WKH UHDFWLRQ VWHS WKH H[SHULPHQWDO VWHDG\ VWDWH FRQYHUVLRQLQWKHFKURPDWRJUDSKLFUHDFWRUGLGQRWRYHUFRPH7KLVYDOXHLVVLJQLILFDQWO\ EHORZWKHHTXLOLEULXPFRQYHUVLRQDW  . ZKLFKLV$VLPXODWLRQVWXG\VXPPDUL]HGLQ )LJXUH  VKRZHG WKDW WKH UHDFWLRQ HTXLOLEULXP FRQYHUVLRQ IRU DQ HTXLPRODU PL[WXUH RI DFHWDOGHK\GH JO\FHURO DQG '062 FRXOG RQO\ EH DFKLHYHG IRU D UHDFWRU VSDFH WLPH RI DSSUR[LPDWHO\  PLQ  )XUWKHUPRUH LW ZDV SRVVLEOH WR GHWHUPLQH WKDW DOWKRXJK WKH FRQYHUVLRQDWWKHVWHDG\VWDWHPXVWQHYHUH[FHHGWKHHTXLOLEULXPFRQYHUVLRQLQWKHWUDQVLHQW VWDWH DV D FRQVHTXHQFH RI WKH FRPELQDWLRQ RI WKH UHDFWLRQ DQG DGVRUSWLRQ SKHQRPHQD DOUHDG\UHSRUWHGIRUWKHIL[HGEHGUHDFWRULWVYDOXHFDQEHPRPHQWDULO\RYHUFRPHUHDFKLQJ DPD[LPXPRIDSSUR[LPDWHO\IRUVSDFHWLPHVKLJKHUWKDQ  PLQ    )LJXUH       (IIHFWRI VSDFH  WLPHRQWKHPD[LPXPDFKLHYDEOHFRQYHUVLRQ IRUWKHV\QWKHVLV RI*($LQDIL[HGEHGDGVRUSWLYHUHDFWRU  = 7 .   =3H DFHWDOGHK\GHJO\FHURO'062 PRODUUDWLRRI   ,Q RUGHU WR FRPSOHPHQW WKH UHSRUWHG ZRUN DQG WR KDYH D GHHSHU XQGHUVWDQGLQJ RI WKH EHKDYLRXURIWKHIL[HGEHGUHDFWRUDQHZVHWRIH[SHULPHQWVZDVSHUIRUPHGE\IHHGLQJDQG HOXWLQJVHYHUDOZDWHU*($'062PL[WXUHVRINQRZQFRPSRVLWLRQWRWKHUHDFWRUDW  . DQG  EDU  7DEOH  SUHVHQWV D VXPPDU\ RI WKH H[SHULPHQWV SHUIRUPHG 7KH VLPXODWHG EUHDNWKURXJK FXUYHV REWDLQHG ZLWK WKH DGVRUSWLRQ SDUDPHWHUV SUHYLRXVO\ HVWLPDWHG DUH SUHVHQWHGIURP)LJXUHWR)LJXUHDORQJZLWKWKHH[SHULPHQWDOGDWD ϮϬй ϰϬй ϲϬй ϴϬй ϭϬϬй ϭ ϭϬ ϭϬϬ ϭϬϬϬ ŽŶǀĞƌƐŝŽŶ ʏ ;ŵŝŶͿ ^ƚĞĂĚLJ^ƚĂƚĞŽŶǀĞƌƐŝŽŶ DĂdžŝŵƵŵŽŶǀĞƌƐŝŽŶ ƋƵŝůŝďƌŝƵŵŽŶǀĞƌƐŝŽŶ * /<&(52/$&(7$/6352'8&7,21%< 6 ,08/$7(' 0 29,1* % (' 5 ($&725      )LJXUH       ([SHULPHQWDODQGVLPXODWHGEUHDNWKURXJKFXUYHVR EWDLQHGE\IHHGLQJ   − ⋅ PRO / RIZDWHU   − ⋅ PRO / RI*($DQG   − ⋅ PRO / RI'062DWDIORZUDWHRI   − ⋅ P/ PLQ WRDIL[HGEHGVDWXUDWHGZLWK   − ⋅ PRO / RIZDWHUDQG   − ⋅ PRO / RI '062DW  .    )LJXUH       ([SHULPHQWDODQGVLPXODWHGEUHDNWKURXJKFXUYHVREWDLQHGE\IHHGLQJ   − ⋅ PRO / RIZDWHUDQG   − ⋅ PRO / RI'062DWDIORZUDWHRI   − ⋅ P/ PLQ WRDIL[HG EHGVDWXUDWHGZLWK   − ⋅ PRO / RIZDWHU   − ⋅ PRO / RI*($DQG   − ⋅ PRO / RI'062 DW  .  ϭϭϬ ϭϭϲ ϭϮϮ ϭϮϴ ϭϯϰ ϭϰϬ ϬϬ Ϭϰ Ϭϴ ϭϮ ϭϲ ϮϬ ϬϬ ϭϬϬ ϮϬϬ ϯϬϬ ϰϬϬ ϱϬϬ ϲϬϬ  D^K ;ŵŽůͼ> Ͳϭ Ϳ ;ŵŽůͼ> Ͳϭ Ϳ dŝŵĞ;ŵŝŶͿ ';džƉͿ ';DŽĚĞůͿ tĂƚĞƌ;džƉͿ tĂƚĞƌ;DŽĚĞůͿ D^K;džƉͿ D^K;DŽĚĞůͿ ϭϭϬ ϭϭϲ ϭϮϮ ϭϮϴ ϭϯϰ ϭϰϬ ϬϬ Ϭϰ Ϭϴ ϭϮ ϭϲ ϮϬ ϬϬ ϭϬϬ ϮϬϬ ϯϬϬ ϰϬϬ ϱϬϬ ϲϬϬ  D^K ;ŵŽůͼ> Ͳϭ Ϳ ;ŵŽůͼ> Ͳϭ Ϳ dŝŵĞ;ŵŝŶͿ ';džƉͿ ';DŽĚĞůͿ tĂƚĞƌ;džƉͿ tĂƚĞƌ;DŽĚĞůͿ D^K;džƉͿ D^K;DŽĚĞůͿ 6 2537,21 ( 1+$1&(' 5 ($&7,9( 3 52&(66)257+( 6 <17+(6,62) *($  7 +( ) ,;(' % (' $ '62537,9( 5 ($&725      )LJXUH       ([SHULPHQWDODQGVLPXODWHGEUHDNWKURXJKFXUYHVREWDLQHGE\IHHGLQJ   − ⋅ PRO / RIZDWHU   − ⋅ PRO / RI*($DQG   − ⋅ PRO / RI'062DWDIORZUDWHRI   − ⋅ P/ PLQ WRDIL[HGEHGVDWXUDWHGZLWK   − ⋅ PRO / RIZDWHUDQG   − ⋅ PRO / RI '062DW  .    )LJXUH       ([SHULPHQWDODQGVLPXODWHGEUHDNWKURXJKFXUYHVREWDLQHGE\IHHGLQJ   − ⋅ PRO / RIZDWHUDQG   − ⋅ PRO / RI'062DWDIORZUDWHRI   − ⋅ P/ PLQ WRDIL[HG EHGVDWXUDWHGZLWK   − ⋅ PRO / RIZDWHU   − ⋅ PRO / RI*($DQG   − ⋅ PRO / RI'062 DW  .  ϭϮϬ ϭϮϰ ϭϮϴ ϭϯϮ ϭϯϲ ϭϰϬ ϬϬ Ϭϰ Ϭϴ ϭϮ ϭϲ ϮϬ ϬϬ ϭϬϬ ϮϬϬ ϯϬϬ ϰϬϬ ϱϬϬ ϲϬϬ  D^K ;ŵŽůͼ> Ͳϭ Ϳ ;ŵŽůͼ> Ͳϭ Ϳ dŝŵĞ;ŵŝŶͿ ';džƉͿ ';DŽĚĞůͿ tĂƚĞƌ;džƉͿ tĂƚĞƌ;DŽĚĞůͿ D^K;džƉͿ D^K;DŽĚĞůͿ ϭϮϬ ϭϮϰ ϭϮϴ ϭϯϮ ϭϯϲ ϭϰϬ ϬϬ Ϭϰ Ϭϴ ϭϮ ϭϲ ϮϬ ϬϬ ϭϬϬ ϮϬϬ ϯϬϬ ϰϬϬ ϱϬϬ ϲϬϬ  D^K ;ŵŽůͼ> Ͳϭ Ϳ ;ŵŽůͼ> Ͳϭ Ϳ dŝŵĞ;ŵŝŶͿ ';džƉͿ ';DŽĚĞůͿ tĂƚĞƌ;džƉͿ tĂƚĞƌ;DŽĚĞůͿ D^K;džƉͿ D^K;DŽĚĞůͿ * /<&(52/$&(7$/6352'8&7,21%< 6 ,08/$7(' 0 29,1* % (' 5 ($&725      'XHWRWKHKLJKYDOXHRIWKHUHDFWLRQWKHUPRG\QDPLFHTXLOLEULXPFRQVWDQWRIWKHVWXGLHG DFHWDOL]DWLRQWKHH[WHQWRIWKHUHYHUVHUHDFWLRQZDVVRORZWKDWRQO\WUDFHVRIWKHUHDFWDQWV FRXOG EH GHWHFWHG DOWKRXJK WKHLU YDOXHV ZHUH EHORZ WKH TXDQWLILFDWLRQ OLPLWV RI WKH DQDO\WLFDOPHWKRGXVHG7KXVDGVRUSWLRQZDVWKHSKHQRPHQRQZLWKJUHDWHULPSDFWLQWKHVH H[SHULPHQWV DQG WKH UHVXOWV SUHVHQWHG ZHUH FRQVLGHUHG WR EH IRFXVHG H[FOXVLYHO\ RQ WKH VHSDUDWLRQRIWKHSURGXFWVRIWKHDFHWDOL]DWLRQUHDFWLRQ 7ZRGLVWLQJXLVKHGIURQWVDUHREVHUYHGIRUDOOVHWVRIH[SHULPHQWDOFRQGLWLRQVWHVWHG$V H[SHFWHGWKURXJKWKHUHVXOWVUHSRUWHGVRIDUZDWHUGHPRQVWUDWHGDKLJKHUDIILQLW\WRZDUGV $PEHUO\VWWKDQ*($DQG'062 )URPWKHREVHUYDWLRQRI)LJXUHWR)LJXUHRQHFDQFRQFOXGHWKDWRQFHDJDLQ WKH PRGHO LV LQ JRRG DJUHHPHQW ZLWK WKH H[SHULPHQWDO GDWD REWDLQHG 7KLV VWDWHPHQW LV FRUURERUDWHGE\WKHFRUUHODWLRQFRHIILFLHQWHTXDWLRQ 7KHUHOHYDQFHRIWKHODWHVWH[SHULPHQWVLVUHODWHGZLWKWKHLQVLJKWWKDWWKH\SURYLGHRYHU WKHEHKDYLRXURIWKHVHSDUDWLRQUHJLRQVRIWKH60%5ZKHUHZDWHU*($DQG'062DUHWKH PDMRU FRPSRXQGV ZKLFK DORQJZLWKLWV UHDFWLRQ]RQH KDYH DGHHS LPSDFW RQ WKHRYHUDOO 60%5SHUIRUPDQFH   &RQFOXVLRQV 7KH LQYHVWLJDWLRQ SUHVHQWHG WKURXJKRXW WKLV &KDSWHU DLPHG WKH DVVHVVPHQW RI WKH V\QWKHVLV RI *($ WKURXJK WKH DFHWDOL]DWLRQ RI JO\FHURO ZLWK DFHWDOGHK\GH LQ D IL[HG EHG DGVRUSWLYHUHDFWRUSDFNHGZLWK$PEHUO\VWZHW)RUWKDWSXUSRVHFRPSOH[PDVVWUDQVIHU DGVRUSWLRQDQGUHDFWLRQSKHQRPHQDPXVWEHDGGUHVVHG 7UDFHUH[SHULPHQWVZHUHFRQGXFWHGLQRUGHUWRVWXG\WKHK\GURG\QDPLFVRIWKHIL[HGEHG DGVRUSWLYH UHDFWRU ,W ZDV SRVVLEOH WR FRQFOXGH WKDW D SOXJ IORZ PRGHO FRQVLGHULQJ D[LDO GLVSHUVLRQ DQG QHJOHFWLQJ GLVSHUVLYH HIIHFWV DORQJ WKH UDGLDO GLPHQVLRQ FRXOG HIIHFWLYHO\ GHVFULEH WKH UHVSRQVH RI WKH XQLW WR DQ LQMHFWLRQ RI WKH WUDFHU IRU IORZUDWHV EHWZHHQ   − ⋅ P/ PLQ DQG   − ⋅ P/ PLQ 7KH3HFOHWQXPEHUZDVXVHGDVDPHDVXUHPHQWRIWKHUDWLR EHWZHHQ WKH FRQYHFWLYH DQG GLVSHUVLYH HIIHFWV IRU ZKLFK DQ DYHUDJH YDOXH RI  ZDV HVWLPDWHG $GVRUSWLRQHTXLOLEULXPGDWDDW  . ZHUHREWDLQHGE\SHUIRUPLQJVHYHUDOEUHDNWKURXJK H[SHULPHQWVZLWKQRQUHDFWLYHSDLUVRIFRPSRXQGVIROORZLQJDIURQWDODQDO\VLVPHWKRGRORJ\ 7KH H[SHULPHQWDO GDWD FROOHFWHG ZHUH ILWWHG E\ D /DQJPXLUFRPSHWLWLYHDGVRUSWLRQ PRGHO 7KHYDOXHVGHWHUPLQHGIRUJO\FHUROZDWHU*($DQG'062DGVRUSWLRQHTXLOLEULXPFRQVWDQWV ZHUH   ±  / PRO − ⋅    ±  / PRO − ⋅    ±  / PRO − ⋅  DQG   ± 6 2537,21 ( 1+$1&(' 5 ($&7,9( 3 52&(66)257+( 6 <17+(6,62) *($  7 +( ) ,;(' % (' $ '62537,9( 5 ($&725      / PRO − ⋅  UHVSHFWLYHO\ 7KHLU PRQROD\HU PD[LPXP FDSDFLWLHV ZHUH   ±  $GV PRO / − ⋅    ±  $GV PRO / − ⋅    ±  $GV PRO / − ⋅ DQG   ±  $GV PRO / − ⋅ E\WKHVDPHRUGHU +HQFHLWLVSRVVLEOHWRFRQILUPWKDW$PEHUO\VWKDVDKLJKVHOHFWLYLW\WRZDUGVZDWHU2Q WKH RWKHU KDQG *($ SUHVHQWHG WKH ORZHVW DGVRUSWLRQ 7KH GHWHUPLQDWLRQ RI DGVRUSWLRQ HTXLOLEULXP GDWD IRU DFHWDOGHK\GH ZDV QRW SRVVLEOH VLQFH WKLV DOGHK\GH UHDFWV IRUPLQJ ROLJRPHUV LQ WKH SUHVHQFH RI DFLGV +RZHYHU WKH H[SHULPHQWDO UHVXOWV LQGLFDWHG WKDW WKH DGVRUSWLRQSDUDPHWHUVHVWLPDWHGIRUJO\FHUROUHSUHVHQWDJRRGHVWLPDWHIRUWKHGHVFULSWLRQRI DFHWDOGHK\GHDGVRUSWLRQHTXLOLEULXP *($ ZDV V\QWKHVLVHG E\ IHHGLQJ   − ⋅ P/ PLQ RI DQ HTXLPRODU PL[WXUH RI DFHWDOGHK\GH JO\FHURO DQG '062 WR D IL[HG EHG DGVRUSWLYH UHDFWRU VDWXUDWHG ZLWK '062 RSHUDWLQJ XQGHU LVRWKHUPDOFRQGLWLRQV$FRQYHUVLRQRIDSSUR[LPDWHO\ZDVDFKLHYHGDWWKHVWHDG\VWDWH 7KHFRQWDFWWLPHEHWZHHQWKHUHDFWDQWVDQGWKHFDWDO\VWSURYHGWREHLQVXIILFLHQWWRUHDFK WKH  UHSUHVHQWLQJ HTXLOLEULXP FRQYHUVLRQ 6LPXODWLRQ VWXGLHV VKRZHG WKDW D VSDFH WLPH DERYH  PLQ ZRXOGEHUHTXLUHGIRUWKDWSXUSRVHDQGWKLVYDOXHFRXOGEHRYHUFRPHE\ LQ D WUDQVLHQW VWDWH DV D FRQVHTXHQFH RI WKH GLIIHUHQW DIILQLW\ RI WKH UHVLQ WRZDUGV HDFK FRPSRXQGLIWKHVSDFHWLPHZDVKLJKHUWKDQ  PLQ  )HHGLQJ D WHUQDU\ PL[WXUH FRQWDLQLQJ ZDWHU *($ DQG '062 WR D IL[HG EHG DGVRUSWLYH UHDFWRUGHPRQVWUDWHGWKDWWKHH[WHQWRIWKHLQYHUVHDFHWDOL]DWLRQUHDFWLRQLVVRORZWKDWLW FDQEHQHJOHFWHG7KHUHIRUHWKHEUHDNWKURXJKFXUYHVREWDLQHGIRUWKHVHFRQGLWLRQVSURYLGHG LPSRUWDQWLQIRUPDWLRQDERXWWKHVHSDUDWLRQRIWKHWHUQDU\PL[WXUHLQDIL[HGEHGZKLFKFDQ EH XVHIXO IRU WKH XQGHUVWDQGLQJ RI WKH EHKDYLRXU RI WKH VHSDUDWLRQ UHJLRQV RI WKH 60%5 SURFHVVLQWHQGHGWREHLPSOHPHQWHGLQWKHQH[W&KDSWHU 6LPXOWDQHRXVO\WRWKHH[SHULPHQWVSHUIRUPHGLQHDFKRIWKHSUHYLRXVO\GHVFULEHGVWDJHV DPDWKHPDWLFDOPRGHOZDVGHYHORSHGLQRUGHUWRHVWLPDWHWKHLQWHUQDOFRQFHQWUDWLRQSURILOHV DQGEUHDNWKURXJKFXUYHVRIDIL[HGEHGDGVRUSWLYHUHDFWRU%HVLGHVWKHDVVXPSWLRQVDOUHDG\ VWDWHGDVWKHLVRWKHUPDORSHUDWLRQWKHSOXJIORZZLWKD[LDOGLVSHUVLRQDQGWKHGHVFULSWLRQRI WKH DGVRUSWLRQ HTXLOLEULXP E\ PXOWLFRPSRQHQW /DQJPXLU LVRWKHUPV WKH PDVV WUDQVIHU ZDV FRQVLGHUHG WR IROORZ D OLQHDU GULYLQJ IRUFH PHFKDQLVP DQG WKH FKHPLFDO UHDFWLRQ ZDV GHVFULEHG E\ WKH/++: PRGHO DFFRUGLQJ WR WKH VWXG\ SUHVHQWHG LQWKH SUHYLRXV &KDSWHU 7KH KLJK YDOXHV GHWHUPLQHG IRU WKH FRUUHODWLRQ FRHIILFLHQW UHJDUGLQJ WKH ILWWLQJ RI WKH H[SHULPHQWDOGDWDDERYHIRUDOOFDVHVFRQILUPVWKHVXLWDELOLW\RIWKHGHYHORSHGPRGHO  