&KURPLXPVWUHVVLQSODQWV
6.3DQGD
DQG6&KRXGKXU\
5HVHDUFK,QVWLWXWHIRU%LRUHVRXUFHV2ND\DPD8QLYHUVLW\.XUDVKLNL±-DSDQ3ODQW%LRFKHPLVWU\/DERUDWRU\6FKRRO
RI/LIH6FLHQFHV$VVDP&HQWUDO8QLYHUVLW\6LOFKDU±,QGLD&RUUHVSRQGLQJDXWKRUGUVNSBDX#\DKRRFRP
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¿FLHQF\LVDQLPSRUWDQWIDFWRULQJHQHUDWLQJR[LGDWLYHVWUHVVLQSODQWVXQGHUFKURPLXPVWUHVV+RZHYHU ERWKPHWDOORWKLRQHLQVDQGRUJDQLFDFLGVDUHLPSRUWDQWLQSODQWVDVFRPSRQHQWVRIWROHUDQFHPHFKDQLVPVDQGDUHDOVRLQYROYHG LQGHWR[L¿FDWLRQRIWKLVWR[LFPHWDO
.H\ZRUGVDQWLR[LGDQWVFKURPLXPIHQWRQUHDFWLRQVPHWDOORWKLRQHLQVR[LGDWLYHVWUHVV
(VWUHVVHGHFURPRHPSODQWDV(VWHDUWLJRDSUHVHQWDXPDUHYLVmRVREUHRPHFDQLPVRGHHVWUHVVHGHFURPRHPSODQWDV2 FURPRpXPPHWDOWy[LFRTXHSRGHFDXVDUVHYHURVGDQRVDSODQWDVHDQLPDLV(VWUHVVHR[LGDWLYRLQGX]LGRSRUFURPRHQYROYH SHUR[LGDomRGHOLStGHRVHPSODQWDVRTXHFDXVDGDQRVVHYHURVjVPHPEUDQDVFHOXODUHV2HVWUHVVHR[LGDWLYRLQGX]LGRSHOR FURPRLQLFLDDGHJUDGDomRGHSLJPHQWRVIRWRVVLQWpWLFRVOHYDQGRjGLPLQXLomRGRFUHVFLPHQWR6XDDOWDFRQFHQWUDomRSRGH FDXVDUGLVW~UELRVjXOWUDHVWUXWXUDGRVFORURSODVWRVHFRQVHTHQWHPHQWHDIHWDURSURFHVVRIRWRVVLQWpWLFR$VVLPFRPRRFREUH HRIHUURRFURPRpWDPEpPXPPHWDOUHGR[HHVVHFRPSRUWDPHQWRH[FHGHRGHRXWURVPHWDLVFRPR&R)H=Q1LHWF2 FRPSRUWDPHQWRUHGR[SRGHHQWmRVHUDWULEXtGRDRGLUHWRHQYROYLPHQWRGRFURPRHPLQGX]LUHVWUHVVHR[LGDWLYRHPSODQWDV2 FURPRSRGHDIHWDURPHWDEROLVPRDQWLR[LGDQWHHPSODQWDV(Q]LPDVDQWLR[LGDQWHVFRPR62'&$732;H*5VmRVXVFHWtYHLV DRFURPRUHVXOWDQGRHPGHFOtQLRGDVVXDVDWLYLGDGHVFDWDOtWLFDV(VVHGHFOtQLRQDH¿FLrQFLDDQWLR[LGDQWHpXPLPSRUWDQWHIDWRU QDJHUDomRGRHVWUHVVHR[LGDWLYRHPSODQWDVVREHVWUHVVHSRUFURPR1RHQWDQWRPHWDORWLRQHtQDVHiFLGRVRUJkQLFRVVmRLPSRU WDQWHVFRPSRQHQWHVHPSODQWDVFRPRPHFDQLVPRVGHWROHUkQFLDHHVWmRHQYROYLGRVQDGHVWR[L¿FDomRGHVVHPHWDOWy[LFR 3DODYUDVFKDYHDQWLR[LGDQWHVFURPRHVWUHVVHR[LGDWLYRPHWDORWLRQHtQDVUHDo}HVGH)HQWRQ
,1752'8&7,21
&KURPLXP &U LV WKH VHYHQWK PRVW DEXQGDQW PHWDO LQ WKH HDUWK¶V FUXVW .DW] DQG 6DOHP DQG DQ LPSRUWDQW HQYLURQPHQWDO FRQWDPLQDQW UHOHDVHG LQWR WKH DWPRVSKHUH GXH WR LWV KXJH LQGXVWULDO XVH 1ULDJX DQG 1LHERHU ,QQDWXUH&UH[LVWVLQWZRGLIIHUHQWVWDEOHR[LGDWLRQVWDWHV WULYDOHQW&U,,,DQGKH[DYDOHQW&U9,FKURPLXP%RWK&U,,,
DQG &U9, GLIIHU LQ WHUPV RI PRELOLW\ ELRDYDLODELOLW\ DQG
WR[LFLW\&U9,LVIRXQGWREHPRUHWR[LFWKDQ&U,,,3DQGDDQG
3DWUD &U9, IRUPV FKURPDWH DQG GLFKURPDWH DQG LV
KLJKO\VROXEOHLQZDWHU&U,,,RQWKHRWKHUKDQGLVOHVVVROXEOH
LQ ZDWHU DQG LV UHTXLUHG LQ WUDFH DPRXQWV DV DQ LQRUJDQLF QXWULHQW IRU DQLPDOV %RWK FKURPDWH DQG GLFKURPDWH DUH FRQVLGHUHG WR EH QHJDWLYHO\ FKDUJHG DQG WKHUH LV D OLPLWHG FKDQFH RI LW EHLQJ DGVRUEHG E\ RUJDQLF PDWHULDOV &U9,LV
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
KDVEHHQVWXGLHGLQPDQ\KLJKHUDQGORZHUSODQWV&U,,,LV
WKRXJKWHVVHQWLDOIRUDQLPDOVLQWUDFHDPRXQWVFDQEHWR[LF DQGLQGXFHVR[LGDWLYHVWUHVV3DQGDDQG3DWUD&U,,,
LV WR[LF WR SODQWV HYHQ DW ORZ FRQFHQWUDWLRQ DQG UHSRUWHG WR FDXVHV VHYHUH R[LGDWLYH GDPDJH WR SODQW FHOOV ,W FDQ DIIHFWJURZWKZDWHUEDODQFHSLJPHQWFRQWHQWDQGLQLWLDWH OLSLG SHUR[LGDWLRQ FDXVLQJ R[LGDWLYH GDPDJH WR SODQWV %RQHWHWDO3RVFKHQULHGHUHWDO%DUFHORDQG
3RVFKHQULHGHU3DQGDDQG3DWUD&U9,RQWKH
RWKHUKDQGLVPRUHSK\WRWR[LFWKDQ&U,,,+DQHWDO
DQG UHWDUGV JURZWK UHGXFHV WKH QXPEHU RI SDOLVDGH DQG VSRQJ\SDUHQFK\PDFHOOVLQOHDYHVDQGLQFUHDVHVWKHQXPEHU RIYDFXROHVDQGHOHFWURQGHQVHPDWHULDODORQJWKHZDOOVRI [\OHPDQGSKORHP+DQHWDO$VDFRQVHTXHQFHRI D ZLGH UDQJH RI DELRWLF VWUHVVHV LQFOXGLQJ KHDY\ PHWDOV WR[LFUHDFWLYHR[\JHQVSHFLHV526OLNH+222+
HWF DUH SURGXFHG +HDY\ PHWDOV XVXDOO\ IRUP 526 HLWKHU GLUHFWO\RUWKURXJKLQYROYHPHQWLQDUHGR[UHDFWLRQ&UZDV WKRXJKWWREHDQRQUHGR[PHWDOWKDWFRXOGQRWSDUWLFLSDWH LQ)HQWRQUHDFWLRQVKRZHYHURWKHUVWXGLHVKDYHVKRZQWKDW &U FDQ LQGHHG SDUWLFLSDWH LQ )HQWRQ UHDFWLRQV SURYLQJ LWV UHGR[ FKDUDFWHU 6KL DQG 'DODO &U UHDFWLYLW\ FDQ EHFRQVLGHUHGIURPLWVLQWHUDFWLRQZLWKJOXWDWKLRQH1$'+ DQG +2IRUPLQJ 2+ UDGLFDOV LQ FHOOIUHH V\VWHPV 6KL
DQG'DODO$L\DUHWDO3URGXFWLRQRI+2
2+ DQG 2
XQGHU &U VWUHVV KDV EHHQ GHPRQVWUDWHG LQ
PDQ\SODQWVJHQHUDWLQJR[LGDWLYHVWUHVVOHDGLQJWRGDPDJH RI '1$ SURWHLQV DQG SLJPHQWV DV ZHOO DV LQLWLDWLQJ OLSLG
SHUR[LGDWLRQ %DJFKL HW DO 3DQGD DQG 3DWUD 3DQGD HW DO 3DQGD &KRXGKXU\ DQG 3DQGD 7KHVRXUFHRIFKURPLXPDQGVXEVHTXHQWLPSRVLWLRQ RIR[LGDWLYHVWUHVVLVVXPPDUL]HGLQ¿JXUH
)LJXUH'LIIHUHQWVRXUFHVRIFKURPLXPDQGWKHLULQYROYHPHQWLQ LQGXFLQJR[LGDWLYHVWUHVVLQSODQWV
&U HIIHFWV LQ UHODWLRQ WR SK\WRWR[LFLW\ KDYH EHHQ LQYHVWLJDWHGE\PDQ\ZRUNHUVRQLPSRUWDQWFURSSODQWVDQG DOVR LQ ORZHU SODQWV OLNH PRVVHV 7XUQHU DQG 5XVW 0F*UDWK9D]TXH]HWDO%LVKQRLHWDO 3DQGDDQG3DWUD3DQGDDQG3DWUD'L[LWHWDO 3DQGDHWDODE3DQGD3DQGDDQG.KDQ 3DQGD HW DO &KRXGKXU\ DQG 3DQGD 3DQGD DQG &KRXGKXU\ +DQ HW DO DQG LW KDV EHHQFOHDUO\GHPRQVWUDWHGWKDW&U9,LVPRUHSK\WRWR[LFWKDQ
&U,,, 3DQGD DQG 3DWUD +DQ HW DO 6RLO DQG
6KDQNHU HW DO &U VWUHVV HVSHFLDOO\ &U9, FDQQRW
LQGXFHSK\WRFKHODWLQV3&VVXJJHVWLQJDUROHIRU07VLQ&U GHWR[L¿FDWLRQDQGWROHUDQFHLQSODQWV6KDQNHUHWDO 7KLV UHYLHZ GHVFULEHV WKH SK\VLRORJLFDO DQG PROHFXODU DVSHFWVRI&UVWUHVVLQSODQWV,WIRFXVHVRQWKHSK\WRWR[LFLW\ RI &U JHQHUDWLQJ R[LGDWLYH VWUHVV YLD 526 DQG DOVR RQ WKH VXEVHTXHQWDQWLR[LGDQWPHWDEROLVPDQGWKHUHGR[EHKDYLRXU RI &U 'HWDLOHG DFFRXQWV RQ KRZ P\FRUKL]DV DQG 07V DUH LQYROYHG LQ &U GHWR[L¿FDWLRQ DQG WROHUDQFH KDYH EHHQ LQFOXGHGLQWKLVUHYLHZ
&KURPLXPWR[LFLW\LQSODQWV
+HDY\PHWDOVOLNH=Q)H&X0QDUHHVVHQWLDOIRUSODQW JURZWK DQG LPSRUWDQW FRQVWLWXHQWV RI PDQ\ HQ]\PHV RI PHWDEROLFLPSRUWDQFH2WKHUPHWDOVOLNH3E&G$V6H&U DQG$ODUHELRORJLFDOO\QRQHVVHQWLDODQGWR[LFDERYHFHUWDLQ WKUHVKROGOHYHOV&ULVWR[LFWRSODQWVDQGGRHVQRWSOD\DQ\ UROHLQSODQWPHWDEROLVP'L[LWHWDO$FFXPXODWLRQ RI&UE\SODQWVFDQUHGXFHJURZWKLQGXFHFKORURVLVLQ\RXQJ OHDYHV UHGXFH SLJPHQW FRQWHQW DOWHU HQ]\PDWLF IXQFWLRQ GDPDJH URRW FHOOV DQG FDXVH XOWUDVWUXFWXUDO PRGL¿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
3K\WRWR[LFHIIHFWVRI&URQSODQWJURZWKKDYHEHHQWKRU RXJKO\VWXGLHGLQPDQ\SODQWVSHFLHVOLNHPRVVHVULFHSHD ZKHDWHWFLQUHODWLRQWRR[LGDWLYHVWUHVV&UH[SRVXUHDWWKH PLFURPRODU UDQJH FDQ OHDG WR VHYHUH SK\WRWR[LF V\PSWRPV LQ SODQW FHOOV %RWK &U,,,DQG &U9, FDQ UHGXFH FKORURSK\OO
FRQWHQWDQGWKHUHE\LQKLELWJURZWK3DQGDDQG3DWUD
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¿FDQWDPRXQWVRI&ULQWKHLUWLVVXHVZLWKGHFUHDVHVLQWKH ELRPDVV RI WKH SODQW 6HQ HW DO *XSWD HW DO 9DMSD\HHHWDO,QDTXDWLFSODQWVXSWDNH DQGELRDFFXPXODWLRQRI&UFDQLQÀ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
9DOOLVQHULD VSLUDOLV DQG RWKHU DTXDWLF SODQWV KRZHYHU DQ LQFUHDVH LQ FDURWHQRLGV FRQWHQW ZDV VHHQ XQGHU &U WUHDW PHQW 5DOSK DQG %XUFKHWW 7ULSDWL DQG 6PLWK 9DMSD\HHHWDO7KHLQFUHDVHLQFDURWHQRLGVFRQWHQW PD\DFWDVDQDQWLR[LGDQWWRVFDYHQJH526JHQHUDWHGDVD UHVXOWRI&UWR[LFLW\
EUDQHVPDNLQJWKHPVXVFHSWLEOHWRR[LGDWLYHGDPDJH3DQGD 8QGHU&UOLSLGSHUR[LGDWLRQFDQEHLQLWLDWHGUHVXOWLQJ LQR[LGDWLYHVWUHVV526WKDWDUHFRPPRQFRQVHTXHQFHVRI PRVWELRWLFDQGDELRWLFVWUHVVHVDUHDOVRIRUPHGDVDUHVXOW &UWR[LFLW\'L[LWHWDO3DQGDHWDO&KRXGKXU\ DQG3DQGD,QPDQ\FURSSODQWVOLNHULFHZKHDWSHD DQGDOVRLQORZHUSODQWVVLJQL¿FDQWLQFUHDVHVLQ526SURGXF WLRQFDQEHREVHUYHGZLWKFRQFRPLWDQWLQFUHDVHVLQOLSLGSHU R[LGDWLRQ3DQGDDQG3DWUD%HKUDHWDO 3DQGDDQG3DWUD'L[LWHWDO3DQGDDQG3DWUD 3DQGD3DQGDHWDO&KRXGKXU\DQG3DQGD +LJKSURGXFWLRQRI+2DQG2UDGLFDOVZHUHUH
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
PD\DOVRELQGWRF\WRFKURPHD'L[LWHWDO$QRWKHU
DOWHUQDWLYHPHFKDQLVPLVWKHJHQHUDWLRQRI2UDGLFDOVLQWKH
PLWRFKRQGULD6FDQGDOLRV9UDQRYDHWDO,QSHD SODQWVWKHWUHDWPHQWRI&UDWGLIIHUHQWFRQFHQWUDWLRQVVKRZHG WKDW 2 LV JHQHUDWHG LQ WKH F\WRFKURPHE UHJLRQ FRPSOH[
,,,RIURRWPLWRFKRQGULD7KH2JHQHUDWLRQDWWKLVVSHFL¿F
VLWHZDVKLJKXQGHU&U'L[LWHWDO7KH&ULQGXFHG LQKLELWLRQRIHOHFWURQWUDQVSRUWLVUHSUHVHQWHGLQ¿JXUH
)HQWRQW\SHDQGUHGR[UHDFWLRQVRIFKURPLXP
7KHR[LGDWLRQUHGXFWLRQRUUHGR[UHDFWLRQVRFFXULQERWK VRLODQGDTXDWLFHQYLURQPHQWV7KH)HQWRQW\SHUHDFWLRQVLQ
YROYHWUDQVLWLRQPHWDOVDQGK\GURJHQSHUR[LGHRUK\GURSHUR[ LGHOHDGLQJWRWKHIRUPDWLRQR[LGL]LQJVSHFLHV*ROGVWHLQDQG &]DVSNL7KHUHGR[UHDFWLRQVWKDWRFFXULQWKHVRLODUH LPSRUWDQWLQDOWHULQJPRELOLW\DQGSK\WRWR[LFLW\7KHLQYROYH PHQW RI FKURPLXP LQ WKH )HQWRQ UHDFWLRQ LV QRW YHU\ ZHOO XQGHUVWRRGRUVWXGLHG6WULOHHWDO%HVLGHWKHZHOO NQRZQUHGR[PHWDOVOLNH&XDQG)H&UDOVRDSSHDUVWRSDU WLFLSDWHLQ5HGR[RU)HQWRQUHDFWLRQV6KLDQG'DODO 7KHR[LGDWLRQVWDWHRI&ULVLPSRUWDQWEHFDXVHWKHFRPPRQ WULSOHWR[LGDWLRQVWDWH&U,,,LVQRWWR[LFDVFRPSDUHGWRWKH
KH[DYDOHQWIRUP&DUWHU0QLQERWKWKHWULYDOHQWDQG WHWUDYDOHQWVWDWHR[LGL]HV&U,,,WR&U9,ZKLOH)H6DQGRUJDQLF
PDWWHULQWKHVRLOFDQUHGXFH&U9,WRWKHPRUHVWDEOHDQGOHVV
SK\WRWR[LF&U,,,&U,,,DQG+
2FDQFDXVHEUHDNDJHRIWKH
'1$VWUDQGDWS+WREXWQRWDWS+DQGLWLVEHOLHYHGWKDW &U,,,DQG&U,,HQWHUVWKH)HQWRQUHDFWLRQ6WULOHHWDO
'XULQJUDGLFDOR[LGDWLRQRI&U,,,&U,9DQG&U9LQWHUPHGLDWHV
DUHWKRXJKWWREHLQYROYHG6WULOHHWDO%HVLGH&U,9
DQG&U9RWKHUVSHFLHVOLNHWKL\O*6DQGK\GUR[\OUDGLFDOV 2+ DUH FRQVLGHUHG WR EH WR[LF DQG FDUFLQRJHQLF $OFHGR
DQG:HWWHUKDKQ7KH(65VWXGLHVDWS+DQGIRU &U,,,+
2VKRZHGWKDWWKHORZHUR[LGDWLRQVWDWHVRI&UFDQ
HIIHFWLYHO\SDUWLFLSDWHLQJHQHUDWLQJR[LGL]LQJVSHFLHVZLWKRXW JHQHUDWLQJ&U9,6WULOHHWDO$WKLJKHUS+WKH
R[LGDWLRQRI&U,,,LVUDSLG$OWKRXJKWKHFRQFHQWUDWLRQ&U9,
UHDFKHVDVWHDG\VWDWHWKHSURGXFWLRQRIR[LGL]LQJVSHFLHVOLNH &U,9DQG&U9SURFHHGVDWDVORZPHDVXUDEOHUDWH6WULOHHWDO
7KLVUHVXOWLQGLFDWHVWKDWERWK&U,9DQG&U9DUHFDWD
O\WLFDOO\ DFWLYH DQG SRVVHVV WKH FDSDELOLW\ WR JHQHUDWH 526
VXFKDVWKHK\GUR[\OUDGLFDO2+6WULOHHWDO7KH
FDWDO\WLFDFWLYLW\RI&U,,,LVPXFKKLJKHULQD)HQWRQUHDFWLRQ
V\VWHPFRPSDUHGWRRWKHUPHWDOVOLNH&R,,&G,,=Q,,0Q,,
DQG)H,,,EXWORZHUWKDQ&X,,6WULOHHWDO
&KURPLXPLQGXFHGR[LGDWLYHVWUHVV
2QHRIWKHFRPPRQUHVSRQVHVWRDZLGHUDQJHRIELRWLF DQG DELRWLF VWUHVVHV LV WKH JHQHUDWLRQ RI UHDFWLYH R[\JHQ VSHFLHVRU526526DUHSURGXFHGLQFHOOVDVDQLQWHUPHGLDWH SURGXFWGXULQJWKHUHGXFWLRQRI2WR+2+HDY\PHWDOVDUH NQRZQWRLQLWLDWH526SURGXFWLRQZKLFKLVLPSOLFDWHGDVD VWUHVVUHVSRQVH'LHW]HWDO&ULVDWR[LFKHDY\PHWDO WKDW FDQ JHQHUDWH 526 OLNH +2 2 2+ ZKLFK FDXVH
R[LGDWLYH GDPDJH WR SODQWV 3DQGD DQG 3DWUD 'L[LWHWDO3DQGD3DQGDDQG.KDQ 3DQGDHWDO&KRXGKXU\DQG3DQGD
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
7D[LWKHOLXPQHSDOHQVHDQG3RO\WULFKXPFRPPXQHH[SRVXUH RI &U LQLWLDWHG WKH SURFHVV RI OLSLG SHUR[LGDWLRQ YLD IUHH UDGLFDOJHQHUDWLRQ&KRXGKXU\DQG3DQGD3DQGDDQG &KRXGKXU\
$QWLR[LGDQW UHVSRQVHV LQ SODQWV WR FKURPLXPLQGXFHG R[LGDWLYHVWUHVV
,Q PRVW RI WKH DHURELF RUJDQLVPV WKHUH LV D QHHG WR HIIHFWLYHO\ HOLPLQDWH WKH WR[LF R[\JHQ VSHFLHV 526 JHQHUDWHGDVDUHVXOWRIHQYLURQPHQWDOVWUHVVHV3ODQWVKDYH GHYHORSHG D FRPSOH[ DQWLR[LGDQW V\VWHP E\ ZKLFK WKH\ VFDYHQJHWKH526WKHUHE\SURWHFWLQJWKHFHOOIURPR[LGDWLYH DWWDFN 526 DUH SURGXFHG DV LQWHUPHGLDWH SURGXFWV LQ D QXPEHURIPHWDEROLFUHDFWLRQVLQYDULRXVFHOOXODURUJDQHOOHV JHQHUDWHG E\ R[LGDWLYH VWUHVV LQ SODQWV ¿JXUH +HDY\ PHWDOV DUH NQRZQ WR JHQHUDWH WKHVH WR[LF 526 VXFK DV +222+2+
HWFZKLFKGHJUDGHLPSRUWDQWFHOOXODU
FRPSRQHQWVE\LQGXFLQJR[LGDWLYHVWUHVV'LHW]HWDO 3DQGD ,Q RUGHU WR FRQWURO WKH OHYHO RI 526 DQG SURWHFWWKHFHOOVIURPR[LGDWLYHLQMXU\SODQWVKDYHGHYHORSHG DFRPSOH[DQWLR[LGDQWGHIHQVHV\VWHPWRVFDYHQJHWKH526 DQGWKHVHDQWLR[LGDQWV\VWHPVLQFOXGHYDULRXVHQ]\PHVDQG QRQHQ]\PHVZKLFKPD\DOVRSOD\DVLJQL¿FDQWUROHLQ526 VLJQDOLQJLQSODQWV9UDQRYDHWDO7KHDQWLR[LGDQW UHVSRQVH RI SODQWV WR PHWDOLQGXFHG R[LGDWLYH VWUHVV LV YDULDEOH DQG GHSHQGV RQ WKH W\SH RI SODQW DQG WKH PHWDO LQYROYHG+RZHYHUXQOLNHRWKHUKHDY\PHWDOVOLNH&G=Q DQG )H LQIRUPDWLRQ RQ WKH DQWLR[LGDQW PHWDEROLVP IRU &U VWUHVVLVVFDUFH
7KH DQWLR[LGDQW HQ]\PHV FDWDODVH &$7 JXDLDFRO SHUR[LGDVH *3[ JOXWDWKLRQH UHGXFWDVH *5 DVFRUEDWH SHUR[LGDVH $3[ DQG VXSHUR[LGH GLVPXWDVH 62' KDYH EHHQ WKRURXJKO\ VWXGLHG IRU SODQWV OLNH ULFH ZKHDW SHD DQGHYHQLQORZHUSODQWVOLNHPRVVHV&$7LVDQLPSRUWDQW KHPHFRQWDLQLQJ HQ]\PH WKDW FDWDO\VHV WKH GLVPXWDWLRQ RI +2 WR +2 DQG R[\JHQ DQG LV ORFDOL]HG LQ WKH SHUR[LVRPHV&$7LVDQLQGLVSHQVDEOHHQ]\PHUHTXLUHGIRU 526GHWR[L¿FDWLRQLQSODQWV$FWLYLW\RI&$7LQUHVSRQVH WR&UKDVEHHQVWXGLHGLQPDQ\FURSSODQWVOLNHULFHZKHDW JUHHQJUDPDQGHYHQLQORZHUSODQWVOLNHPRVVHV3DQGDDQG 3DWUD3DQGDDQG'DVK3DQGDDQG3DWUD 3DQGD 3DQGD HW DO 3DQGD DQG &KRXGKXU\&KRXGKXU\DQG3DQGD,QULFH&U FDQHLWKHULQGXFH&$7DFWLYLW\RUVXSSUHVVLW7UHDWPHQWRI GHYHORSLQJZKHDWVHHGOLQJVWRGLIIHUHQWFRQFHQWUDWLRQVRI&U VKRZHGYDULHGUHVSRQVHV,QPRVWRIWKHVWXGLHVFRQGXFWHG D JUDGXDO GHFUHDVH LQ &$7 DFWLYLW\ ZDV REVHUYHG LQ SODQWV
ZKLOHLQPRVVHVERWKDOOHYLDWLRQDQGGHFOLQHZDVREVHUYHG 3DQGDDQG3DWUD3DQGD3DQGDHW DO 3DQGD DQG &KRXGKXU\ &KRXGKXU\ DQG3DQGD,QZKHDWUHVSRQVHWR&UZDVDOVRYDULDEOH ([SRVXUHRI&UWRGHYHORSLQJZKHDWVHHGOLQJVGHFUHDVHGWKH &$7DFWLYLW\DIWHUGDQGGRI&UWUHDWPHQWDWDQG P0 3DQGD DQG 3DWUD 0RUHRYHU DW PXFK KLJKHU FRQFHQWUDWLRQV DQG P0 VHYHUH LQKLELWLRQ LQ &$7 DFWLYLW\ZDVREVHUYHGDIWHUGDQGGRI&UWUHDWPHQW3DQGD HWDO$VLPLODULQKLELWLRQRI&$7ZDVUHSRUWHGZKHQ &U ZDV VXSSOLHG LQ DGGLWLRQ WR QLWURJHQ QXWULWLRQ LQ ZKHDW 3DQGDHWDO
0HFKDQLVPRIFKURPLXPGHWR[L¿FDWLRQWKHSRVVLEOHUROH RIPHWDOORWKLRQLQHVDQGRUJDQLFDFLGV
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¿FDWLRQLQSODQWVDQGLWKDVEHHQUHSRUWHGIRUVRUJKXP WKDW07OLNHSURWHLQVDUHH[SUHVVHGXQGHU&UVWUHVV6KDQNHU HWDO07VDUHWKHSURGXFWRIP51$WUDQVODWLRQDQG DUH FKDUDFWHUL]HG DV ORZ PROHFXODU ZHLJKW F\VWHLQHULFK PHWDOELQGLQJSURWHLQ.DJL7KHUROHRI07VRUHYHQ 3&V LQ &U GHWR[L¿FDWLRQ LQ SODQWV KDV QRW EHHQ WKRURXJKO\ VWXGLHG FRPSDUHG WR WKDW RWKHU KHDY\ PHWDOV OLNH &G +J &X HWF DQG FRQVHTXHQWO\ WKHUH LV YHU\ OLWWOH LQIRUPDWLRQ DERXWWKHLQYROYHPHQWRIWKHVHPHWDOELQGLQJOLJDQGVLQ&U GHWR[L¿FDWLRQLQSODQWV$VWXG\RI&U9,HIIHFWVRQWKH07
JHQH H[SUHVVLRQ XVLQJ &U WROHUDQW DQG VXVFHSWLEOH YDULHWLHV UHYHDOHGDKLJKLQWHQVLW\EDQGPDWFKLQJWKHJHQHRILQWHUHVW LQ WKH WROHUDQW YDULHW\ FRPSDUHG WR WKH VXVFHSWLEOH RQH 6KDQNHUHWDO7KLVVXJJHVWVWKDWXQGHU&UVWUHVV WKHUHFRXOGEHKLJKWUDQVFULSWLRQUDWHVRI07VSDUWLFXODUO\ LQ WKH WROHUDQW YDULHW\ 6KDQNHU HW DO 7KH UROH RI 3&VLQUHJXODWLQJPHWDOWR[LFLW\KDVEHHQUHSRUWHGLQSODQWV ,WZDVVXJJHVWHGWKDWWKHSURGXFWLRQRI526DQG+2DVD UHVXOWRI&UH[SRVXUHPLJKWKDYHWULJJHUHGVLJQDOVWRLQGXFH 07P51$WUDQVFULSWLRQ6KDQNHUHWDO7KXV07V
PD\KDYHDYHU\LPSRUWDQWUROHLQ&UGHWR[L¿FDWLRQLQSODQWV SRVVLEO\ E\ ELQGLQJ &U LRQV DQG PDNLQJ WKHP QRQWR[LF +RZHYHUWKHUROHRI07VLQ&UGHWR[L¿FDWLRQLQSODQWVLVQRW ZHOOXQGHUVWRRGQRUWKRURXJKO\VWXGLHGVRWKHLUUROHLQWKLV UHVSHFWVWLOOUHPDLQVDFKDOOHQJHIRUWKHIXWXUH
7KHURRWFRQWDLQVRUJDQLFDFLGVWKDWELQGWRPHWDOVIURP KLJKO\LQVROXEOHIRUPVLQWKHVRLODQGDFLGVOLNHFLWULFDFLGDQG PDOLFDFLGVFDQDFWDVHVVHQWLDOOLJDQGVIRUPHWDOV5DXVHU 7KH UROH RI FLWULF DFLG LQ UHJXODWLQJ$O ,,, DQG 1L ,,
GHWR[L¿FDWLRQLQSODQWVKDVEHHQFOHDUO\GHPRQVWUDWHG<DQJ HW DO 7KH URRW H[XGDWHV DUH YHU\ LPSRUWDQW DJHQWV WKDWIRUPFRPSOH[HVZLWKWUDFHPHWDOVDQGDIIHFWWKHLUUHGR[ EHKDYLRXU +DOH DQG *ULI¿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¿FDQWUROHLQ&U GHWR[L¿FDWLRQLVVWLOOQRWFRPSOHWHO\XQGHUVWRRG
&21&/86,21
7KH XQGHUVWDQGLQJ RI WKH EDVLF PHFKDQLVP LQYROYHG LQ FKURPLXP XSWDNH WUDQVSRUW DFFXPXODWLRQ DQG GHWR[L¿FDWLRQ LQSODQWVWRJHWKHUZLWKLWVSK\VLRORJLFDOHIIHFWVLVQHFHVVDU\IRU WKHSK\WRUHPHGLDWLRQRIWKHFKURPLXPSROOXWHGHQYLURQPHQWV XVLQJPROHFXODUDQGJHQHWLFWHFKQLTXHV7KHVHDSSURDFKHVPD\ LQFOXGHWKHLGHQWL¿FDWLRQRIK\SHUDFFXPXODWRUVWKDWFDQSURYLGH HI¿FLHQW SK\WRUHPHGLDWLRQ RI FKURPLXPSROOXWHG VRLOV WKH VWXG\RIELRFKHPLFDODQGPROHFXODUUHVSRQVHVRIWKHVHSODQWV WRFKURPLXPDQGWKHLGHQWL¿FDWLRQRIJHQHVWKDWH[SUHVV3&VRU 07VLQYROYHGLQWKHGHWR[L¿FDWLRQRIWKHPHWDOZLWKLQWKHSODQW 7KHVHWHFKQRORJLHVZLOOSURYHXVHIXOLQHQYLURQPHQWDOFOHDQXS SURFHGXUHVDQGVXEVHTXHQWUHVWRUDWLRQRIVRLOIHUWLOLW\
5()(5(1&(6
$OFHGR-$:HWWHUKDKQ5&KURPLXPWR[LFLW\DQGFDU FLQRJHQHVLV,Q5LFKWHU*:6ROH].$LVHQ3&RKHQ* HGV,QWHUQDWLRQDOUHYLHZRIH[SHULPHQWDOSDWKRORJ\SS $FDGHPLF3UHVV1HZ<RUN
$WWD$O\0$6KHKDWD1*.REELD70(IIHFWRIFREDOW RQWRPDWRSODQWJURZWKDQGPLQHUDOFRQWHQW$QQ$JULO 6FL&DLUR
%DJFKL&-RVKL66%DJFKL0%DOPRRUL-%HQQHU(-.XV]\Q VNL&$&DGPLXP±DQG&KURPLXP±LQGXFHGR[ LGDWLYHVWUHVV'1$GDPDJHDQGDSRSWRWLFFHOOGHDWKLQ FXOWXUHGKXPDQFKURQLFP\HORJHQRXVOHXNHPLF.FHOO SURP\HORF\WLFOHXNHPLF+/±FHOOVDQGQRUPDOKXPDQ SHULSKHUDOEORRGPRQRQXFOHDUFHOOV-%LRO0RO7R[LFRO ±
%DUFHOR-3RVFKHQULHGHU&&KURPLXPLQSODQWV,Q &DUDWL67RWWDUHOOL)6HTPL3HGV&KURPLXPHQYLURQ PHQWDOLVVXHSS±)UDQFRWDQJDWL3UHVV0LODQ %DUOHWW5-&KURPLXPF\FOLQJLQVRLODQGZDWHU/LQNV
JDSVDQGPHWKRGV(QYLURQ+HDOWK3HUVS± %DUOHWW5--DPHV%50RELOLW\DQGELRDYDLODELOLW\RI
FKURPLXPLQVRLOV,Q1ULDJX-21LHERHU(HGV&KURPL XPLQQDWXUDODQGKXPDQHQYLURQPHQWSS±-RKQ :LOH\DQG6RQV,QF1HZ<RUN
%DV]\QVNL7.URO0:ROLQND'(IIHFWRIFKURPDWH RQSKRWRV\QWKHWLFDSSDUDWXVRI/HPQDPLQRU/,Q$NR\ QRJORX * HG 3KRWRV\QWKHVLV ,, (OHFWURQ WUDQVSRUW DQG SKRWRSKRVSKRU\ODWLRQSS±%DOERQ,QWHUQDWLRQDO 6FLHQFH6HUYLFHV
%DVVL0&RUUDGL0*5HDOLQL0(IIHFWVRIFKURPL XP9,RQWZRIUHVKZDWHUSODQWV/HPQDPLQRUDQG3LV WLDVWUDWLRWHV0RUSKRORJLFDOREVHUYDWLRQV&\WRELRV ±
%LVKQRL15$QLWD'*XSWD9.6KDZDQH\6.(I IHFWRIFKURPLXPRQVHHGJHUPLQDWLRQVHHGOLQJJURZWKDQG \LHOGRISHDV$JULF(FRO(FRV\W±
%RQHW$3RVFKHQULHGHU&%DUFHOR-&KURPLXP,,,LRQ LQWHUDFWLRQLQ)HGH¿FLHQWDQG)HVXI¿FLHQWEHDQSODQWV, *URZWKDQG1XWULHQWFRQWHQW-3ODQW1XWU± &DOWDGR'$0F)DGGHQ.07KRPDV5*DUODQG:LOGGXQJ
5(2UJDQLFFRQVWLWXHQWDQGFRPSOH[DWLRQRI1LFN HO,,&DGPLXP,,DQG3OXWRQLXP9,LQVR\EHDQ[\ OHPH[XGDWHV3ODQW3K\VLRO±
&DUWHU'(2[LGDWLRQUHGXFWLRQRIPHWDOLRQV(QYL URQ+HDOWK3HUVS±
&KRXGKXU\63DQGD6.7R[LFHIIHFWVR[LGDWLYHVWUHVV DQGXOWUDVWUXFWXUDOFKDQJHVLQPRVV7D[LWKHOLXPQHSDOHQVH 6FKZDHJU%URWKXQGHUFKURPLXQDQGOHDGSK\WRWR[LFL W\:DWHU$LU6RLO3ROOXW6XEPLWWHG
&RUUDGL0*%LDQFKL$$OEDVLQL$&KURPLXPWR[ LFLW\LQ6DOYLDVFODUHD(IIHFWVRIKH[DYDOHQWFKURPLXP RQVHHGJHUPLQDWLRQDQGVHHGOLQJGHYHORSPHQW(QYLURQ ([S%RW±
&REEHWW&*ROGVEURXJK33K\WRFKHODWLQVDQGPHWDO ORWKLRQHLQV5ROHLQKHDY\PHWDOGHWR[L¿FDWLRQDQGKRPH RVWDVLV$QQ5HY3ODQW%LRO±
&REEHWW&3K\WRFKHODWLQVDQGWKHLUUROHLQKHDY\PHW DOGHWR[L¿FDWLRQ3ODQW3K\VLRO±
'DYLV-U)73XU\HDU-'1HZWRQ5-(JLOOD-1*URVVL-$6 0\FRUKL]DOIXQJLHQKDQFHVDFFXPXODWLRQDQGWRO HUDQFHRIFKURPLXPLQVXQÀRZHU+DOLDQWKXVDQQXXV -3ODQW3K\VLRO
'L[LW93DQGH\96K\DP5&KURPLXPLRQVLQDFWL YDWHHOHFWURQWUDQVSRUWDQGHQKDQFHVXSHUR[LGHJHQHUDWLRQ LQYLYRLQSHD3LVXPVDWLYXP/FY$]DGURRWPLWRFKRQ GULD3ODQW&HOO(QY
'LHW].-%DLHU0.UDPHU8)UHHUDGLFDOVDQGUHDF WLYHR[\JHQVSHFLHVDVPHGLDWRURIKHDY\PHWDOWR[LFLW\LQ SODQWV,Q3UDVDG019+DJHPH\HU-HGV+HDY\PHWDO VWUHVVLQSODQWV)URPPROHFXOHVWRHFRV\VWHPSS± 6SULQJHU±9HUODJ%HUOLQ
*ROGVWHLQ6&]DVSNL*7UDQVLWLRQPHWDOVDQGR[\JHQ UDGLFDOV,Q5LFKWHU*6ROH].$LVHQ3&RKHQ*HGV ,QWHUQDWLRQDO UHYLHZ RI H[SHULPHQWDO SDWKRORJ\ SS $FDGHPLF3UHVV1HZ<RUN
*XSWD06LQKD6&KDQGUD38SWDNHDQGWR[LFLW\RI PHWDOLQ6FULSXVODFXVWULV/-(QYLURQ6FL+HDOWK
+DOH 0* *ULI¿Q *- (IIHFW RI LQMXU\ RQ H[XGDWLRQ IURPLPPDWXUHDQGPDWXUHSODQWIUXLWV3ODQW3K\VLRO$E VWUDFWV
+DQ);6ULGKDU%%00RQWV'/6X<3K\WRDYDLO DELOLW\DQGWR[LFLW\RIWULYDOHQWDQGKH[DYDOHQWFKURPLXP WR%UDVVLFDMXQFHD1HZ3K\WRO
-DPHV%5%DUOHWW5-%HKDYLRURIFKURPLXPLQVRLOV 9,,QWHUDFWLRQVEHWZHHQR[LGDWLRQ±UHGXFWLRQDQGRUJDQ LFFRPSOH[DWLRQ-(QYLURQ4XDO
.DJL-+52YHUYLHZRIPHWDOORWKLRQHLQ0HWKRGV(Q ]\PRO
.DW]6$6DOHP+7KHELRORJLFDODQGHQYLURQPHQWDO FKHPLVWU\RIFKURPLXP9HUODJVJHVHOOVFKDIWPE+:HLQ KHLP3DSSHODOODH3RVWIDFK
.UXSD=%DV]\QVNL76RPHDVSHFWRIKHDY\PHWDOWR[ LFLW\WRZDUGVSKRWRV\QWKHWLFDSSDUDWXV±GLUHFWDQGLQGL UHFWHIIHFWRIOLJKWDQGGDUNUHDFWLRQV$FWD3K\VLRO3ODQW
/LX'+-DLQJ:6/L0;(IIHFWRIFKURPLXPRQURRW JURZWKDQGFHOOGLYLVLRQRI$OOLXPFHSD,VUDHO-3ODQW6FL
0F*UDWK637KHXSWDNHDQGWUDQVORFDWLRQRIWLQDQG KH[DYDOHQWFKURPLXPDQGHIIHFWVRQWKHJURZWKRIRDWLQ ÀRZHULQJ QXWULHQW VROXWLRQ DQG LQ VRLO 1HZ 3K\WRO
0F*UDWK63&KURPLXPDQG1LFNHO,Q$OORZD\%-HGV+HDY\PHWDOVLQVRLOSS&KDSPDQDQG+DOO /RQGRQ8.
1D\DUL+)6]DODL7.DGDU,&DVWKR3*HUPLQDWLRQ FKDUDFWHULVWLFV RI SHD VHHGV RULJLQDWLQJ IURP D ¿HOG WUL DOWUHDWHGZLWKGLIIHUHQWOHYHORIKDUPIXOHOHPHQWV$FWD $JURQ+XQJ
1LHERHU(5LFKDUGVRQ'+67KHUHSODFHRIWKHQRQ GHVFULSWWHUPKHDY\PHWDOV!!E\DELRORJLFDOO\DQG FKHPLFDOO\VLJQL¿FDQWFODVVL¿FDWLRQRIPHWDOLRQV(QYL URQ3ROOXW6HU%
15&>1DWLRQDO5HVHDUFK&RXQFLO@&RPPLWWHHRQEL RORJLFDOHIIHFWRIDWPRVSKHULFSROOXWDQWVFKURPLXP1DWO $FDG6FL:DVKLQJWRQ'&
3DQGD6.3DUWD+.3K\VLRORJ\RIFKURPLXPWR[LFLW\LQ SODQWV±$5HYLHZ3ODQW3K\VLRO%LRFKHP 3DQGD 6. 3DWUD +. $OWHUDWLRQ RI QLWUDWH UHGXFWDVH
DFWLYLW\E\FKURPLXPLRQVLQH[FLVHGZKHDWOHDYHV,QG-$JULF%LRFKHP
3DQGD6.'DVK05HJXODWLRQRIVHQHVFHQFHE\&U9, LRQVLQH[FLVHGZKHDWOHDYHV-1DW%RW6RF 3DQGD6.3DWUD+.'RHV&U,,,SURGXFHVR[LGDWLYHGDP
DJHLQH[FLVHGZKHDWOHDYHV-3ODQW%LRO 3DQGD6.0DKDSDWUD63DWUD+.&KURPLXPWR[LF
LW\DQGZDWHUVWUHVVVLPXODWLRQHIIHFWVLQLQWDFWVHQHVFLQJ OHDYHVRIJUHHQJUDP9LJQDUDGLDWD/YDU:LOFN]HFN. ,Q3DQGD6.HG$GYDQFHVLQVWUHVVSK\VLRORJ\RISODQWV SS6FLHQWL¿F3XEOLVKHUV,QGLD
3DQGD6..KDQ0+$QWLR[LGDQWHI¿FLHQF\LQULFH 2U\]DVDWLYD/OHDYHVXQGHUKHDY\PHWDOWR[LFLW\-3ODQW %LRO
3DQGD6.+HDY\PHWDOSK\WRWR[LFLW\LQGXFHVR[LGDWLYH VWUHVVLQ7D[LWKHOLXPVS&XUU6FL
3DQGD6.&KDXGKXU\,.KDQ0++HDY\PHWDOVLQ GXFHOLSLGSHUR[LGDWLRQDQGDIIHFWVDQWLR[LGDQWVLQZKHDW OHDYHV%LRO3ODQW
3DQGD 6. &KRXGKXU\ 6 &KDQJHV LQ QLWUDWH UHGXFW DVH15DFWLYLW\DQGR[LGDWLYHVWUHVVLQPRVV3RO\WULFKXP FRPPXQHVXEMHFWHGWRFKURPLXPFRSSHUDQG]LQFWR[LFL W\%UD]-3ODQW3K\VLRO6XEPLWWHG
3DQGD6.7KHELRORJ\RIR[LGDWLYHVWUHVVLQJUHHQFHOOV $5HYLHZ,Q3DQGD6.HG$GYDQFHVRIVWUHVVSK\VLRORJ\ RISODQWVSS6FLHQWL¿F3XEOLVKHUV-KRGSXU,QGLD 3DQGD6.&KRXGKXU\6&KDQJHVLQQLWUDWHUHGXFWDVH
DFWLYLW\OLSLGSHUR[LGDWLRQDQGDQWLR[LGDQWV\VWHPLQPRVV
3RO\WULFKXPVSVXEMHFWHGWRKH[DYDOHQWFKURPLXPWUHDW PHQW%UD]O-3ODQW3K\VLRO6XEPLWWHG06 3RVFKHQULHGHU &9D]TXH] 0' %RQHW$ %DUFHOR - &KURPLXP,,,LURQLQWHUDFWLRQLQLURQVXI¿FLHQWDQGLURQ GH¿FLHQW EHDQ SODQWV ,, 8OWUDVWUXFWXUDO DVSHFWV - 3ODQW 1XWU
5DL 817ULSDWL 5' .XPDU 1 %LRDFFXPXODWLRQ RI FKURPLXPDQGWR[LFLW\RQJURZWKSKRWRV\QWKHWLFSLJPHQWV SKRWRV\QWKHVLVLQYLYRQLWUDWHUHGXFWDVHDFWLYLW\DQGSUR WHLQLQDFKORURFRFFDOHDQJUHHQDOJD*ODXFRF\VWLVQRVWRFKL QHDUXP,W]LJVRKQ&KHPRVSKHUH
5DOSK 3- %XUFKHWW 0' 3KRWRV\QWKHWLF UHVSRQVH RI
+DORSKLOD RYDOLV WR KHDY\ PHWDO VWUHVV (QYLURQ 3ROOXW
5R\6,KDQWROD5+DQQLHQ23HUR[LGDVHDFWLYLW\LQ ODNH PDFURSK\WHV DQG LWV UHODWLRQ WR SROOXWLRQ WROHUDQFH (QYLURQ([S%RW
6KL;'DODO16&KURPLXP9DQGK\GUR[\OUDGLFDOIRU PDWLRQGXULQJWKHJOXWDWKLRQHUHGXFWDVH±FDWDO\]HGUHGXFWLRQ RIFKURPLXP9,%LRFKHP%LRSK\V5HV
6RORPRQVRQ/3%DUEHU0-$VVLPLODWRU\QLWUDWHUHGXFW DVHIXQFWLRQDOSURSHUWLHVDQGUHJXODWLRQ$QQ5HY3ODQW 3K\VLRODQG3ODQW0RO%LRO
6HQ$. 0RQGRO 1* 0RQGDO 6 6WXGLHV RI XSWDNH DQGWR[LFHIIHFWVRI&U9,RQ3LVLWDVWUDWLRLWHV:DW6FL 7HFK
6WULOH0.RODU-6HOLK96.RFDU'3LKODU%$FRP SDUDWLYHVWXG\RIVHYHUDOWUDQVLWLRQPHWDOVLQ)HQWRQOLNH UHDFWLRQV\VWHPDWFLUFXP±QHXWUDOS+$FWD&KLQ6ORY
6ULYDVWDYD66ULYDVWDYD63UDNDVK66ULYDVWDYD00 )DWHRIWULYDOHQWFKURPLXPLQSUHVHQFHRIRUJDQLFDFLGV &KHP6SHF%LRDYDLO
6KDQNHU$.'MDQDJXLUDPDQ06XGKDJDU5-D\DUDP.3DWK PDQDEKDQ*([SUHVVLRQRIPHWDOORWKLRQHLQV±OLNH SURWHLQP51$LQVRUJKXPFXOWLYDUVXQGHUFKURPLXP9, VWUHVV&XUU6FL
6FDQGDOLRV-*2[\JHQVWUHVVDQGVXSHUR[LGHGLVPXWDVH 3ODQW3K\VLRO
7XUQHU0$5XVW5+(IIHFWVRIFKURPLXPRQJURZWK DQGPLQHUDOQXWULWLRQRIVR\EHDQ6RLO6FL6RF$PPHU 3URF
7ULSDWL5'6PLWK6(IIHFWRIFKURPLXP9,RQJURZWK DQGSK\VLRORJ\RIJLDQWGXFNZHHG6SLURGHOODSRO\UUKL]D
/6FKLOHLGHQ,Q<XQXV016LQJK/GH.RN-HGV (QYLURQPHQWDO 6WUHVV ,QGLFDWLRQ 0LWLJDWLRQ DQG (FR ± &RQVHUYDWLRQSS.OXZHU$FDGHPLF3XEOLVKHUV 7KH1RUWKODQGV
9DMSD\HH36KDUPD6&5DL817ULSDWL5'<XQXV0 %LRDFFXPXODWLRQRIFKURPLXPDQGWR[LFLW\WRSKRWRV\QWKHW LFSLJPHQWVQLWUDWHUHGXFWDVHDFWLYLW\DQGSURWHLQFRQWHQWRI 1HOXPERQXFLIHUD*DHWUQ&KHPRVSKHUH 9DMSD\HH37ULSDWL5'5DL81$OL0%6LQJK61
&KURPLXPDFFXPXODWLRQUHGXFHVFKORURSK\OOELRV\QWKHVLV QLWUDWHUHGXFWDVHDFWLYLW\DQGSURWHLQFRQWHQWRI1\PSKDHD
DOED&KHPRVSKHUH
9DMSD\HH35DL81$OL0%7ULSDWL5'<DGDY96LQKD6 6LQJK61&KURPLXP±LQGXFHGSK\VLRORJLFFKDQJ HVLQ9DOOLVQHULDVSLUDOLV/DQGLWVUROHLQSK\WRUHPHGD WLRQRIWDQQHU\HIÀXHQWV%XOO(QYLURQ&RQW7R[LFRO
9RQ%XUJ5/LX'&KURPLXPDQGKH[DYDOHQWFKUR PLXP-$SSO7R[LFRO
9UDQRYD(,Q]H'9DQ%UHXVHJHP)6LJQDOWUDQVGXF WLRQGXULQJR[LGDWLYHVWUHVV-([S%RW 9D]TXH]0'3RVFKHQULHGHU&%DUFHOR-&KURPLXP
9,LQGXFHGVWUXFWXUDOFKDQJHVLQEXVKEHDQSODQWV3KDVH ROXVYXOJDULV/$QQ%RW
<DQJ01:DQJ-:DQJ6+;X//6DOLF\OLFDFLGLQ GXFHDOXPLQXPWROHUDQFHE\PRGXODWLRQRIFLWUDWHHIÀX[
IURPURRWVRI&DVVLDWRUD/3ODQWD