HAL Id: hal-02141343
https://hal.archives-ouvertes.fr/hal-02141343
Submitted on 17 Jul 2019HAL is a multi-disciplinary open access archive for the deposit and dissemination of sci-entific research documents, whether they are pub-lished or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers.
L’archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d’enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
Distributed under a Creative Commons Attribution| 4.0 International License
Optimizing the Heck-Matsuda Reaction in Flow with a
Constraint-Adapted Direct Search Algorithm
Daniel Cortes-Borda, Ksenia V. Kutonova, Corentin Jamet, Marina E.
Trusova, Francoise Zammattio, Charlotte Truchet, Mireia Rodriguez-Zubiri,
Francois-Xavier Felpin
To cite this version:
Daniel Cortes-Borda, Ksenia V. Kutonova, Corentin Jamet, Marina E. Trusova, Francoise Zammattio, et al.. Optimizing the Heck-Matsuda Reaction in Flow with a Constraint-Adapted Direct Search Algorithm. Organic Process Research and Development, American Chemical Society, 2016, 20 (11), pp.1979-1987. �10.1021/acs.oprd.6b00310�. �hal-02141343�
ϭ
2SWLPL]LQJWKH+HFN0DWVXGD5HDFWLRQLQ)ORZZLWKD&RQVWUDLQW$GDSWHG
'LUHFW6HDUFK$OJRULWKP
'DQLHO&RUWpV%RUGDDE.VHQLD9.XWRQRYDF&RUHQWLQ-DPHWD0DULQD(7UXVRYDF)UDQoRLVH =DPPDWWLRD&KDUORWWH7UXFKHWE0LUHLD5RGULJXH]=XELULD)UDQoRLV;DYLHU)HOSLQ DG
D8QLYHUVLWpGH1DQWHV8)5GHV6FLHQFHVHWGHV7HFKQLTXHV&156805/,1$UXHGH
OD+RXVVLQLqUH1DQWHV&HGH[)UDQFH
E8QLYHUVLWpGH1DQWHV8)5GHV6FLHQFHVHWGHV7HFKQLTXHV&156805&(,6$0UXH
GHOD+RXVVLQLqUH1DQWHV&HGH[)UDQFH
F 'HSDUWPHQW RI %LRWHFKQRORJ\ DQG 2UJDQLF &KHPLVWU\ 1DWLRQDO 5HVHDUFK 7RPVN 3RO\WHFKQLF
8QLYHUVLW\7RPVN5XVVLD
G,QVWLWXW8QLYHUVLWDLUHGH)UDQFHUXH'HVFDUWHV3DULV&HGH[)UDQFH
Ϯ
ϯ
$EVWUDFW
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
.H\ZRUGV
ϰ
,QWURGXFWLRQ
)RU GHFDGHV FKHPLVWV KDYH PDLQO\ IRFXVHG WKHLU FUHDWLYLW\ RQ FKHPLFDO SURFHVVHV ZKLOH SD\LQJ OLWWOH DWWHQWLRQ WR WKH UHDFWLRQ YHVVHO $V D FRQVHTXHQFH WKH YDVW PDMRULW\ RI V\QWKHWLF ZRUNUHSRUWHGVRIDUKDYHEHHQLQYHQWHGLQEDWFKDOWKRXJKPDQ\VXFFHVVIXOWUDQVSRVLWLRQVXQGHU IORZ FRQGLWLRQV KDYH EHHQ UHSRUWHG WKHVH ODVW \HDUV )ORZ FKHPLVWU\ RIIHUV PDQ\ VLJQLILFDQW LPSURYHPHQWVRYHUEDWFKFKHPLVWU\VXFKDVEHWWHUPDVVDQGKHDWWUDQVIHUHIILFLHQWPL[LQJVDIHW\ HQKDQFHPHQW UHGXFHG UHDFWLRQ WLPH DQG ZDVWH KLJKHU UHSURGXFLELOLW\ DV ZHOO DV EHQHILWV UHVXOWLQJIURPDXWRPDWLRQ7KHPLQLDWXUL]DWLRQRIIORZGHYLFHVPDNHVWKHPSHUIHFWO\VL]HGIRU WKH VFUHHQLQJ DQG RSWLPL]DWLRQ RI UHDFWLRQV LQYROYLQJ KLJK DGGHG YDOXH FRPSRXQGV VXFK DV HODERUDWHGLQWHUPHGLDWHVRUH[SHQVLYHRUJDQRPHWDOOLFFDWDO\VWV
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
$ PXFK PRUH DSSHDOLQJ VWUDWHJ\ FRQVLVWV LQ LQWHJUDWLQJ D IHHGEDFN ZLWK LQWHOOLJHQW DOJRULWKPV 7KLV DSSURDFK HQDEOHV RSWLPL]DWLRQ V\VWHPV WR DQDO\]H SUHYLRXV UHDFWLRQ GDWD LQ RUGHUWRDGDSWDQGPRGLI\WKHIROORZLQJH[SHULPHQWVLQDVKRUWWLPHIUDPH7KLVUHVHDUFKOLQH KDVEHHQSLRQHHUHGE\GH0HOORDQGFRZRUNHUVIRUWKHV\QWKHVLVRI&G6HQDQRSDUWLFOHVDQGXS WR QRZ WKH JURXSV RI -HQVHQ 3ROLDNRII &URQLQ /H\ /DSNLQ DQG %RXUQH KDYH FRQWULEXWHG WR WKLV HPHUJLQJ EXW VWLOO XQH[SORUHG UHVHDUFK DUHD 7KH FKDOOHQJH DVVRFLDWHG ZLWK
ϱ
LQWHOOLJHQWRSWLPL]DWLRQV\VWHPVUHVXOWVLQWKHQHHGWRSHUIRUPDFRQVWUDLQHGRSWLPL]DWLRQZLWKRXW NQRZOHGJHDQGDSULRULRQWKHYDOXHRIUHDFWLRQSDUDPHWHUVPDNLQJWKHRSWLPL]DWLRQRIFRPSOH[ UHDFWLRQVDFKDOOHQJHEH\RQGFODVVLFDORSWLPL]DWLRQWHFKQLTXHV
2SWLPL]DWLRQ RI UHDFWLRQV LQYROYLQJ RUJDQRPHWDOOLF FDWDO\VWV DUH XVXDOO\ WLPHFRQVXPLQJ VLQFHWKHRSWLPDOFRQGLWLRQVGHSHQGQRWRQO\RQWKHYDOXHRIZHOONQRZQSDUDPHWHUVLQFOXGLQJ WKHWHPSHUDWXUHWLPHDQGFRQFHQWUDWLRQEXWDOVRLQPDQ\H[DPSOHVRQWKHXVHRIDGGLWLYHVVXFK DVEDVHDQGOLJDQGDPRQJRWKHUV2XUWHDPKDVDORQJVWDQGLQJLQWHUHVWIRUSDOODGLXPFDWDO\]HG +HFN UHDFWLRQV LQYROYLQJ DUHQHGLD]RQLXP VDOWV DV DU\ODWLQJ DJHQWV DQG ZH GHYHORSHG VHYHUDO PHWKRGRORJLHVERWKLQEDWFKDQGIORZPRGHVIROORZLQJDWUDGLWLRQDOHPSLULFDODSSURDFKIRU UHDFWLRQVRSWLPL]DWLRQ:KLOHWKH3GFDWDO\]HGDU\ODWLRQRIDFWLYDWHGDONHQHVVXFKDVDFU\ODWHVRU VW\UHQHVZLWKGLD]RQLXPVDOWVLVQRZZHOOPDVWHUHGWKHDU\ODWLRQRIXQDFWLYDWHGDF\FOLFDONHQHV LVRQHRIWKHV\QWKHWLFFKDOOHQJHVLQWKLVUHVHDUFKOLQHWKDWKDVEHHQSLRQHHUHGE\WKHWHDPVRI &RUUHLDDQG6LJPDQ:HDOVRUHFHQWO\UHSRUWHGRXURZQFRQWULEXWLRQWRWKLVUHVHDUFKDUHDZLWK WKHGHYHORSPHQWRIDVLPSOHFDWDO\WLFV\VWHPXVLQJS\ULGLQHPHWKDQRODVLQH[SHQVLYHOLJDQG )URPWKHVHVWXGLHVZHOHDUQHGWKDWWKHDU\ODWLRQRIDF\FOLFDONHQHVLUHTXLUHVWKHXVHRIDOLJDQG IRUVWDELOL]LQJ3GFRPSOH[HVDQGLLKDVRQO\IRXQGVXFFHVVLQEDWFKPRGHZKLOHWKHXVHRIIORZ FRQGLWLRQV UHPDLQ XQNQRZQ 7KHUHIRUH ZH ZRQGHUHG LI WKH EHWWHU PDVV DQG KHDW WUDQVIHU DQG HIILFLHQW PL[LQJ RIIHUHG E\ IORZ FKHPLVWU\ FRXOG DOORZ 3GFDWDO\]HG DU\ODWLRQ RI XQDFWLYDWHG DONHQHVZLWKGLD]RQLXPVDOWVZLWKRXWWKHXVHRI DQ\ DGGLWLYHLQFOXGLQJEDVHDQGOLJDQGIRUWKH VDNHRIZDVWHUHGXFWLRQH[SHULPHQWDOVLPSOLFLW\DQGHQYLURQPHQWDOFRQFHUQV:HUHDVRQHGWKDW IRUWDFNOLQJVXFKDFKDOOHQJLQJWDVNZLWKXQFHUWDLQFKDQFHVRIVXFFHVVWKHXVHRIDQRSWLPL]LQJ DOJRULWKPLQWHJUDWLQJD IHHGEDFNLQWRWKHRSWLPL]DWLRQFRXOGVSHHGXSWKHSURFHVVDQGLQFUHDVH WKHRSSRUWXQLW\RIILQGLQJDGHTXDWHH[SHULPHQWDOFRQGLWLRQV ,QWKLVSDSHUZHGHVFULEHRXUUHFHQWILQGLQJVRQWKHXVHRIDPRGLILHG6LPSOH[DOJRULWKPIRU WKHRSWLPL]DWLRQRID+HFN0DWVXGDUHDFWLRQLQDIORZGHYLFHLQYROYLQJWKHDU\ODWLRQRIEXWHQ GLRO2XUZRUNFXOPLQDWHGZLWKWKHRSWLPL]DWLRQRIWKH FRXSOLQJZLWKDVWRQLVKLQJO\VLPSOH H[SHULPHQWDO FRQGLWLRQV QRW UHTXLULQJ DQ\ DGGLWLYH LQFOXGLQJ EDVH DQG OLJDQG 0RUHRYHU WKH PRGLILHGVLPSOH[DOJRULWKPVKRZHGJUHDWIOH[LELOLW\VLQFHWKHH[SHULPHQWDOFRQGLWLRQVFRXOGEH WXQHG DFFRUGLQJ WR WKH QDWXUH RI WKH REMHFWLYH IXQFWLRQ ZKLFK FRXOG EH HLWKHU WKH \LHOG WKH SURGXFWLYLW\PJKRUWKHXQLWDU\FRVW¼J
ϲ
5HVXOWVDQGGLVFXVVLRQ
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
DSSDUHQWIRUPDWLRQRI3G13VDIWHUPLQRIVWLUULQJ7KHH[SHULPHQWDOVHWXSFRQVLVWHGLQWZR ZD\VHTXLSSHGZLWKP/ORRSV6FKHPH/RRS$ZDVORDGHGZLWKDVROXWLRQRIDQGLQ '0)0H2+ZLWKDFRQFHQWUDWLRQRI0DQGORRS%ZDVILOOHGZLWKDVROXWLRQRI3G7)$LQ
ϳ
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³EODFN ER[´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
ϴ
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
)LJXUH *HRPHWULFDO WUDQVIRUPDWLRQV RI WKH VLPSOH[ D UHIOHFWLRQ E H[SDQVLRQ F LQVLGH
FRQWUDFWLRQGRXWVLGHFRQWUDFWLRQHVKULQN
6LQFH WKH 1HOGHU0HDG DOJRULWKP KDV QRW EHHQ LQLWLDOO\ GHYHORSHG IRU WKH VSHFLILFLWLHV RI FKHPLFDO UHDFWLRQV LW ZDV PRGLILHG DQG LPSOHPHQWHG LQ 0DWODE WR L KDQGOH WKH UHVWULFWLRQV LPSRVHGE\WKHXSSHUDQGORZHUERXQGVRIYDULDEOHVDQGLLGLYHUVLI\WKHVHDUFKWRHVFDSHIURP ORFDORSWLPDDQGILQGEHWWHURSWLPDSRWHQWLDOO\WKHJOREDORSWLPXPLQPXOWLRSWLPDIXQFWLRQV 7KHIORZGLDJUDPRIWKHPRGLILHGPHWKRGLVJLYHQLQ)LJXUH
ϵ
)LJXUH)ORZGLDJUDPRIWKHDGDSWHG1HOGHU0HDGRSWLPL]DWLRQDOJRULWKP
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
ϭϬ
VLPSOH[HVDUHDOVRQRWVXLWDEOHVLQFHWKHVHDUFKPLJKWEHLQWHUUXSWHGSUHPDWXUHO\ZKHQLWUHDFKHV WKH ERXQGDU\ RI WKH IHDVLEOH GRPDLQ RI WKH IXQFWLRQ 7\SLFDOO\ WKH LQLWLDO VLPSOH[ LV JLYHQ E\ IL[LQJ RQH RI WKH YHUWLFHV RI WKH VLPSOH[ DV D UDQGRP SRLQW ;RLQ WKH IHDVLEOH GRPDLQ RI WKH
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ۏ ێ ێ ێ ۍܺͳܺͳ ݀ ܺͳ ܺʹ ܺʹ ܺʹ ݀ ڮ ܺ݊ ܺ݊ ܺ݊ ڭ ڭ ڰ ڭ ܺͳ ܺʹ ڮ ܺ݊ ݀ےۑ ۑ ۑ ې 7DEOH9DOXHVRIWKHYDULDEOHVLQWKHIHDVLEOHGRPDLQ
9DULDEOH /RZHUERXQG 8SSHUERXQG
7HPSHUDWXUH&
5HVLGHQFHWLPHPLQ
(TXLYDOHQWRI
&DWDO\VWORDGLQJPRO
&RQVWUDLQW DGDSWDWLRQV 7KH 1HOGHU0HDG 6LPSOH[ PHWKRG LV D GLUHFW VHDUFK RSWLPL]DWLRQ DOJRULWKPIRUXQFRQVWUDLQHGSUREOHPV+RZHYHUWKHYDULDEOHVRIFKHPLFDOUHDFWLRQVDUHOLPLWHG E\ SK\VLFDO FKHPLFDO DQG HFRQRPLF IDFWRUV UHTXLULQJ WR UHVWULFW WKH VHDUFK VSDFH 7KH XVXDO VWUDWHJ\WRUHVWULFWWKHUHVHDUFKVSDFH FRQVLVWVLQLPSRVLQJSHQDOWLHVRQWKHSRLQWVYLRODWLQJWKH
ϭϭ
UHVWULFWLRQV IRUFLQJ WKH VLPSOH[ WR UHPDLQ ZLWKLQ WKH GHOLPLWHG GRPDLQ +RZHYHU ZKHQ WKH RSWLPXPOLHVRQWKHERXQGDU\ZKLFKLVYHU\OLNHO\LQRXUFDVHWKHPHWKRGUHTXLUHVVXFFHVVLYH FRQWUDFWLRQVDQGQXPHURXVHYDOXDWLRQIXQFWLRQVWRSODFHWKHSRLQWRQWKHERUGHUVHH)LJXUH6 ,QRUGHUWRUHGXFHWKHQXPEHURIFRVWO\H[SHULPHQWVZHPRGLILHGWKHDOJRULWKPWRFRQWUDFWWKH VLPSOH[E\SURMHFWLQJWKHSRLQWIDOOLQJRXWRIWKHIHDVLEOHGRPDLQRQWKHERXQGDU\DVVKRZQLQ )LJXUHRQDVLPSOLILHGGLPHQVLRQH[DPSOH
)LJXUH 0RGLILFDWLRQ RI WKH 1HOGHU0HDG PHWKRG WR SURMHFW WKH SRLQWV IDOOLQJ RXW RI WKH
IHDVLEOH GRPDLQ RQ WKHERXQGDU\ 7KH UHIOHFWHG SRLQW $¶ OHDGV WR DQ H[SDQVLRQ $¶¶ RXW RI WKH IHDVLEOHGRPDLQZKLFKLVSURMHFWHGRQWKHERXQGDU\DW$¶¶
'LPHQVLRQDOLW\ UHGXFWLRQ RI WKH VHDUFK ,W LV ZRUWK PHQWLRQLQJ WKDW LQ DQ QGLPHQVLRQ SUREOHPRQO\XSWRQSRLQWVRIWKHVLPSOH[FDQEHSURMHFWHGRQWKHERXQGDU\VLQFHSURMHFWLQJWKH
QSRLQWVRQWKHERXQGDU\ZRXOGLSUHYHQWWKHVLPSOH[IURPHVFDSLQJIURPWKHERXQGDU\LI UHTXLUHG DQGLL DIIHFW WKHFRQYH[LW\RIWKHVLPSOH[)LJXUH67RSUHYHQWWKHPHWKRGIURP SURMHFWLQJ PRUH WKDQ Q SRLQWV RI WKH VLPSOH[ RQ WKH ERXQGDU\ ZH PRGLILHG WKH DOJRULWKP WR
ϭϮ
UHGXFHWKHGLPHQVLRQRIWKHVHDUFKDQGH[SORUHWKHERXQGDU\ZKHUHWKHQSRLQWVDUHSURMHFWHG 2XU PRGLILFDWLRQ FRQVLVWV LQ VWRSSLQJ WKH QGLPHQVLRQ 1HOGHU0HDG VHDUFK ZKHQ WKH PHWKRG DWWHPSWVWRSURMHFWWKHQWKSRLQWVRQWKHERXQGDU\DQGVWDUWLQJDQHZQGLPHQVLRQVHDUFK RYHUWKHERXQGDU\ZKHUHWKHQSRLQWVRIWKHVLPSOH[DUHSURMHFWHGVHHVXSSRUWLQJLQIRUPDWLRQIRU GHWDLOV)LJXUHV66
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
ϭϯ
)LJXUH 'LPHQVLRQ UHSUHVHQWDWLRQ RI WKH WUDQVODWLRQ RI WKH UHIOHFWHG VLPSOH[ LQ RUGHU WR
UHFRYHU WKH GLPHQVLRQ RI WKH VHDUFK 7KH VLPSOH[ $¶%¶& LV UHIOHFWHG SHUSHQGLFXODUO\ WR WKH XSSHU ERXQG RI YDULDEOH DQG WUDQVODWHG WRZDUGV WKH RSWLPXP IRXQG RQ WKH ERXQGDU\ FRQVWUDLQHGRSWLPXP7KHGLPHQVLRQVHDUFKUHVWDUWVZLWKWKHVLPSOH[0127KHSHQDOWLHV RQWKHH[SORUHGUHJLRQVRIWKHERXQGDU\IRUFHWKHUHIOHFWHGSRLQW1¶ WRFRQWUDFWWRZDUGV1¶
6WRSSLQJFULWHULD7\SLFDOO\WKH1HOGHU0HDGVHDUFKLVWHUPLQDWHGLZKHQHLWKHUWKHVLPSOH[ JHWVVPDOOHQRXJKDURXQGWKHRSWLPXPRULLWKHVWDQGDUGGHYLDWLRQRIWKHIXQFWLRQYDOXHVDWWKH YHUWLFHVDUHYHU\VPDOOUHTXLULQJDQH[WHQVLYHQXPEHURIH[SHULPHQWV:LWKWKHDLPRIUHGXFLQJ WKH QXPEHU RI H[SHQVLYH H[SHULPHQWV ZH DGGLWLRQDOO\ LPSOHPHQWHG WKH IROORZLQJ VWRSSLQJ FULWHULDFRQVLGHULQJWKDWWKHVHDUFKVWRSVZKHQDQ\RIWKHVWRSSLQJFULWHULDLVUHDFKHG
LLL,IWKHREMHFWLYHIXQFWLRQLVERXQGHGE\DNQRZQH[SHFWHGYDOXHHJRIUHDFWLRQ\LHOG WKHVHDUFKVWRSVZLWKRXWSHUIRUPLQJIXUWKHUH[SHULPHQWV
LY 7KH PHWKRG VWRSV DIWHU KDYLQJ SHUIRUPHG D SUHGHILQHG PD[LPXP QXPEHU RI IXQFWLRQ HYDOXDWLRQV7KHEHVWSRLQWREWDLQHGDORQJWKHH[SORUDWLRQLVFRQVLGHUHGDVWKHRSWLPXPEXWWKH & $¶ %¶ 2 2¶ 0 1 0¶ 1¶ 9D UL D E OH 9DULDEOH 7UDQVODWLRQ 5HIOHFWLRQ 1¶ *OREDORSWLPXP &RQVWUDLQHGRSWLPXP 1HOGHU0HDGIXQ HYDO 5HVWULFWLRQV 3HQDOL]HGSRLQWV
ϭϰ
XVHU PLJKW FRQVLGHU LW XVHIXO WR UHVWDUW WKH PHWKRG IURP D QHZ UDQGRP SRLQW WR ILQG RWKHU SRWHQWLDORSWLPDLQWKHXQH[SORUHGGRPDLQ
Y 1HDUE\ DQ RSWLPXP WKH VLPSOH[ FRQWUDFWV DQG VKULQNV XQWLO DOO WKH YHUWLFHV RI WKH VLPSOH[ DSSURDFK WR WKH RSWLPXP $V WKLV SURFHVV FRVWV QXPHURXV IXQFWLRQ HYDOXDWLRQV ZH VWRS WKH VHDUFK ZKHQ WKH EHVW UHVXOW REWDLQHG LV QRW LPSURYHG DIWHU Q FRQVHFXWLYH VLPSOH[HV WKH QXPEHURIVLPSOH[HVLVGLIIHUHQWIURPWKHQXPEHURIH[SHULPHQWVIRUGHWDLOVSOHDVHUHIHUWRWKH VXSSRUWLQJ LQIRUPDWLRQ 7KH QXPEHU RI DOORZHG DWWHPSWV WR UHSODFH WKH RSWLPXP Q FRUUHVSRQGVWRWKHQXPEHURIWKHYHUWLFHVRIWKHVLPSOH[PHDQLQJWKDWHDFKSRLQWKDVDWOHDVWRQH RSSRUWXQLW\ WR EH UHSODFHG 7KLV VKRUWFXW VWRSSLQJ FULWHULRQ LV PHDQW WR UHDFK QHDU RSWLPDO RU RSWLPDOUHVXOWVZLWKLQDORZQXPEHURIIXQFWLRQHYDOXDWLRQV,WLVDFWLYDWHGLQWZRFDVHVHLWKHU ZKHQWKHVLPSOH[IDOOVLQDYDOOH\RIWKHREMHFWLYHIXQFWLRQZLWKRXWLPSURYLQJWKHUHVXOWRUZKHQ WKH VHDUFK LV IRFXVHG LQ WKH QHLJKERUKRRG RI DQ RSWLPD ZLWK DV\PSWRWLFDO LPSURYHPHQW RI WKH UHVXOW ,Q ERWK FDVHV WKH XVHU LQ WKH IHHGEDFN VWDJH FRXOG VWLOO GHFLGH WR FRQWLQXH YLD GLYHUVLILFDWLRQLQFDVHRIIDOOLQJLQDYDOOH\RIWKHREMHFWLYHIXQFWLRQRUYLDLQWHQVLILFDWLRQLQ FDVHRIIDOOLQJLQWKHQHLJKERUKRRGRIDQRSWLPD
8VHU GHFLVLRQ ,QWHQVLILFDWLRQ GLYHUVLILFDWLRQ DQG WHUPLQDWLRQ 2SWLPL]DWLRQ SUREOHPV WUHDWHG DV D ³EODFN ER[´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
ϭϱ
LL'LYHUVLILFDWLRQ7KH1HOGHU0HDGPHWKRGLVDGLUHFWVHDUFKRSWLPL]DWLRQDOJRULWKPZKLFK LVQRWDEOHWRHVFDSHIURPDORFDORSWLPXP,QRUGHUWRHVFDSHIURPDORFDORSWLPXPDQGGLYHUVLI\ WKHVHDUFKWKHXVHUFDQGHFLGHWRUHVWDUWWKH1HOGHU0HDGPHWKRGIURPDUDQGRPSRLQWRXWVLGH RI WKH H[SORUHG GRPDLQ ZKLOH XVLQJ SHQDOWLHV WR SUHYHQW WKH DOJRULWKP IURP IDOOLQJ LQ DOUHDG\ H[SORUHGUHJLRQV7KLVPXOWLVWDUWVWUDWHJ\LVVXLWDEOHWRWDFNOHPXOWLRSWLPDREMHFWLYHIXQFWLRQV
LLL 7HUPLQDWLRQ 7KH XVHU FDQ GHFLGH WR VWRS WKH PHWKRG ZLWKRXW SHUIRUPLQJ DQ\ IXUWKHU H[SHULPHQW ZKHQ HLWKHU WKH QXPEHU RI HYDOXDWLRQV LV WRR KLJK RU WKH UHVXOW REWDLQHG ILOOV WKH H[SHFWDWLRQV
,WLVZRUWKPHQWLRQLQJWKDWWKHDOJRULWKPLVDEOHWRUXQDXWRPDWLFDOO\ZLWKRXWXVHULQWHUDFWLRQ :H FRQVLGHU KRZHYHU WKDW WKH XVHU IHHGEDFN LV FHUWDLQO\ D JXDUDQWHH IRU REWDLQLQJ WKH EHVW SRVVLEOHUHVXOWLQDPLQLPXPQXPEHURIH[SHULPHQWV
2SWLPL]DWLRQ RI WKH +HFN0DWVXGD UHDFWLRQ 7KH PRGLILHG 1HOGHU0HDG DOJRULWKP ZDV
XVHGIRUWKHRSWLPL]DWLRQRIWKUHHGLIIHUHQWREMHFWLYHIXQFWLRQHJLPD[LPL]DWLRQRIWKH\LHOG LLPD[LPL]DWLRQRIWKHSURGXFWLYLW\H[SUHVVHGDVPJKDQGLLLPLQLPL]DWLRQRIWKHSURGXFWLRQ FRVWH[SUHVVHGDV¼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
ϭϲ
2SWLPXPLL PJK
2SWLPXPLLL ¼J
L0D[LPL]DWLRQRIWKH\LHOG)URPWKHLQLWLDOH[SHULPHQWVIRUPLQJWKHILUVWVLPSOH[WKHEHVW
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
ϭϳ
)LJXUHD5HVXOWVRIWKHPD[LPL]DWLRQRIWKH\LHOGLQGLPHQVLRQE5HSUHVHQWDWLRQRIWKH
GLPHQVLRQH[SHULPHQWDOFRQGLWLRQVRIWKHPD[LPL]DWLRQRIWKH\LHOG
LL0D[LPL]DWLRQRIWKH WKURXJKSXWPJK:KLOHLQEDWFKWKHPD[LPL]DWLRQRIWKH \LHOGLV
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
ϭϴ WRVWRSWKHRSWLPL]DWLRQLQWKHIHHGEDFNVWDJHRIWKHDOJRULWKP7KHDOJRULWKPUHTXLUHGRQO\ H[SHULPHQWV)LJXUHELQFOXGLQJWKHGLPHQVLRQUHGXFWLRQDQGGLPHQVLRQUHFRYHU\WRUHDFKWKH VWRSSLQJFULWHULRQVHH7DEOH6LQ6XSSRUWLQJ,QIRUPDWLRQIRUGHWDLOVRQWKHH[SHULPHQWV )LJXUHD5HVXOWVRIWKHPD[LPL]DWLRQRIWKHWKURXJKSXW7KHLQLWLDOVLPSOH[FRUUHVSRQGVWR
WKH GLPHQVLRQ VHDUFK DQG SRLQWV WR WKH GLPHQVLRQ VHDUFK E 5HSUHVHQWDWLRQ RI WKH GLPHQVLRQH[SHULPHQWDOFRQGLWLRQVRIWKHPD[LPL]DWLRQRIWKHWKURXJKSXW
LLL 0LQLPL]DWLRQ RI WKH SURGXFWLRQ FRVW RI SURGXFW ¼J :KLOH WKH PD[LPL]DWLRQ RI WKH
WKURXJKSXWLVDQLPSRUWDQWSDUDPHWHUUHODWHGWRWKHUHDFWLRQHIILFLHQF\LWGRHVQRWFRQVLGHUWKH FRVWRIWKHSURGXFWV\QWKHVLV,QWKHLQGXVWULDOHQYLURQPHQWERWKWKHWKURXJKSXWDQGWKHFRVWDUH FUXFLDOSDUDPHWHUVIRUHYDOXDWLQJWKHHFRQRPLFYLDELOLW\RIDV\QWKHVLV7KHPD[LPL]DWLRQRIWKH \LHOGRUWKHWKURXJKSXWRIDFDWDO\WLFUHDFWLRQDUHRIWHQSODJXHGE\DKLJKORDGLQJRIWKHFDWDO\VW ZKLFKLVXVXDOO\DQH[SHQVLYHUHDJHQW2XURSWLPL]DWLRQVDUHQRH[FHSWLRQVLQFHRXUFRQGLWLRQV
ϭϵ
UHODWHG WR WKH EHVW \LHOG DQG KLJKHVW WKURXJKSXW UHTXLUH DQG PRO 3G UHVSHFWLYHO\ 7KHUHIRUH ZH GHFLGHG WR RSWLPL]H WKH SURGXFWLRQ FRVW 3& RI SURGXFW ZKLFK LV JLYHQ E\ HTXDWLRQZKHUH(LVWKHSRZHUFRQVXPSWLRQHOHFWULFLW\DQG&LVWKHFRVWRIFKHPLFDOVVWDUWLQJ PDWHULDOV DQG FDWDO\VW SHU JUDP RI FRPSRXQG SURGXFHG ( ZDV FRPSXWHG DV WKH SRZHU FRQVXPSWLRQRIWZRSXPSV(SDQGDQRYHQ(RZKLOH&LVWKHDGGLWLRQRIWKHFRVWRIGLD]RQLXP
VDOW&GVGLRO&GDQG3GFDWDO\VW&3G7KHSRZHUFRQVXPSWLRQRIWKHSXPSVDQGRYHQDUH
JLYHQDVDIXQFWLRQRIWLPHLQHTXDWLRQVDQGUHVSHFWLYHO\ ZKHUH :SDQG :RLVWKHDYHUDJH
SRZHU RI WKH SXPSV DQG RYHQ UHVSHFWLYHO\ W LV WKH WLPH DQG &H LV WKH FRVW RI HOHFWULFLW\ ¼N:K IRU )UDQFH LQ :LWK IORZ UDWHV UDQJLQJ IURP WR POPLQ WKH SRZHU FRQVXPSWLRQ:SZDVPHDVXUHGDVN:SHUSXPSZKLOHWKHDYHUDJHSRZHUFRQVXPSWLRQRI WKHRYHQLQN:LVJLYHQE\DOLQHDUIXQFWLRQRIWKHWHPSHUDWXUHLQHTXDWLRQLQWKHRSHUDWLRQDO UDQJHRIWR& ܲܥ ൌ ܧ ܥ ܧ ൌ ܹ ݐ ܥ ܧ ൌ ܹ ݐ ܥ ܹ ൌ ͲǤͲͲͳܶ െ ͲǤͲ͵͵ͻ 5HJDUGLQJWKHFRVWRIFKHPLFDOVZHQHJOHFWHGWKHVROYHQWVDQGWKHFRVWRIVWDUWLQJPDWHULDOV DQGFDWDO\VWPDWHULDOVZDVHVWDEOLVKHGDVIROORZGLD]RQLXPVDOW ¼JGLRO ¼J DQG3GFDWDO\VW ¼J7KHREMHFWLYHRIWKLVVWXG\ZDVWRVKRZWKHSRZHURIDOJRULWKPWR KHOSFKHPLVWVLQPLQLPL]LQJWKHFRVWRIDFKHPLFDOV\QWKHVLVEXWZHZHUHDZDUHWKDWWKHYDOXHV FRPSXWHG UHIOHFWHG DQ LQFRPSOHWH SDUW RI WKH FRVW VLQFH VHYHUDO SDUDPHWHUV LQFOXGLQJ LVRODWLRQ SXULILFDWLRQWUDQVSRUWDWLRQDQGVDODU\H[SHQVHVZHUHQRWFRQVLGHUHG
$IWHU WKH LQLWLDO VLPSOH[ WKH RSWLPL]DWLRQ VWDUWHG ZLWKRXW IDOOLQJ LQ WKH ERXQGDULHV RI WKH IHDVLEOH GRPDLQ DQG QR GLPHQVLRQDOLW\ UHGXFWLRQ ZDV UHTXLUHG $IWHU H[SHULPHQWV WKH DOJRULWKP IRXQG D SRWHQWLDO RSWLPXP FRUUHVSRQGLQJ WR FD ¼J )LJXUH D 7KH DOJRULWKP FRQWLQXHG WKH VHDUFK DQG JHQHUDWHG Q VLPSOH[HV FRUUHVSRQGLQJ WR H[SHULPHQWV EXW XQIRUWXQDWHO\ ZLWKRXW LPSURYLQJ WKH UHVXOW 6LQFH WKLV YDOXH ZDV FRQVLGHUHG XQDFFHSWDEOH ZH GHFLGHGWRFRQWLQXHWKH VHDUFK YLDWKHIHHGEDFNVWDJHWRLPSURYHWKHUHVXOWDWWKHH[SHQVHRI QHZ H[SHULPHQWV LQWHQVLILFDWLRQ $ QHZ RSWLPXP SRLQW FRUUHVSRQGLQJ WR FD ¼J ZDV
ϮϬ
ORFDWHGDWWKHWKH[SHULPHQWDQGWKHPHWKRGVHDUFKVWRSSHGEHFDXVHWKHH[SORUDWLRQUHDFKHGWKH SUHGHILQHGPD[LPXPQXPEHURIH[SHULPHQWVDFFHSWHGE\WKHXVHUH[SHULPHQWV)LJXUHE VKRZVWKHH[SHULPHQWDOFRQGLWLRQVRIWKHSRLQWVQRWLQJWKDWWKHPDMRULPSURYHPHQWVRQWKH UHVXOWVDUHDWWDLQHGLQWKHILUVWH[SHULPHQWVVHH7DEOH6LQ6XSSRUWLQJ,QIRUPDWLRQIRUGHWDLOV 5HPDUNDEO\ LQ WKLV VWXG\ ZH ZHUH DEOH WR UHGXFH WKH SURGXFWLRQ FRVW E\ D IDFWRU RI DSSUR[LPDWHO\IURPFDWR¼JLQRQO\H[SHULPHQWV
)LJXUHD5HSUHVHQWDWLRQRIWKHGLPHQVLRQH[SHULPHQWDOFRQGLWLRQVRIWKHPLQLPL]DWLRQRI
WKHSURGXFWLRQFRVWRIE5HVXOWVRIWKHPLQLPL]DWLRQRIWKHSURGXFWLRQFRVWRISURGXFWZLWK D±GLPHQVLRQVHDUFK
Ϯϭ
&RQFOXVLRQ
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
([SHULPHQWDOVHFWLRQ
0DWHULDOV $OO FRPPHUFLDO UHDJHQWV ZHUH XVHG DV UHFHLYHG IURP 6LJPD$OGULFK )LVFKHU
6FLHQWLILF /WG DQG $OID $HVDU ([WUD SXUH PHWKDQRO DQG '0) ZHUH XVHG ZLWKRXW IXUWKHU SXULILFDWLRQ 0HWKRGV3XULILFDWLRQRISURGXFWZDVFDUULHGRXWE\IODVKFROXPQFKURPDWRJUDSK\XVLQJVLOLFD JHO±PP$QDO\WLFDOWKLQOD\HUFKURPDWRJUDSK\7/&ZDVSHUIRUPHGRQPPVLOLFD JHO)SODWHV9LVXDOL]DWLRQZDVDFFRPSOLVKHGXVLQJD89ODPSQP+DQG&105 VSHFWUDZHUHUHFRUGHGDW0+]DQG0+]UHVSHFWLYHO\DQGWKH\DUHUHSRUWHGDVįYDOXHV SSP UHODWLYH WR UHVLGXDO &'&O į + SSP DQG &'&O į & SSP DV LQWHUQDO
VWDQGDUGV/RZUHVROXWLRQPDVVVSHFWURVFRS\/506ZDVSHUIRUPHGXVLQJFKHPLFDOLRQL]DWLRQ &,+LJKUHVROXWLRQPDVVVSHFWURVFRS\+506ZDVUHFRUGHGRQDQRUELWUDSVSHFWURPHWHU7KH *&DQDO\VHVZHUHSHUIRUPHGRQD*&),'$JLOHQW$FKURPDWRJUDSKHTXLSSHGZLWKDP +3 FDSLOODU\ FROXPQ 7KH *&06 DQDO\VHV ZHUH UHFRUGHG RQ D 75$&( *& 8OWUD 7KHUPR6FLHQWLILFDSSDUDWXVHTXLSSHGZLWKDP7506VLOLFDFDSLOODU\FROXPQDQGD'64,,
ϮϮ TXDGUXSROHDQDO\VHU7KHUPR6FLHQWLILF6DPSOHORRSVDQGUHDFWRUVZHUHPDGHRXWRI3((.ZLWK DPPLQWHUQDOGLDPHWHU7PL[HUVZHUHPDGHRXWRI3((.ZLWKDQLQWHUQDOYROXPHRIȝ/ DQGFRQQHFWLQJWXELQJZDVPDGHRXWRI3)$ZLWKDPPLQWHUQDOGLDPHWHU 5HDFWLRQVHWXSIRUWKH2SWLPL]DWLRQRIWKH+HFNí0DWVXGD5HDFWLRQ8VLQJD)ORZ'HYLFH 7KHH[SHULPHQWDOVHWXSFRQVLVWHGLQWZRZD\VHTXLSSHGZLWKP/ORRSV$'0)0H2+ VROXWLRQ RI EXWHQGLRO 0 DQG WKH UHTXLUHG DPRXQW RI FKORUREHQ]HQH GLD]RQLXP WHWUDIOXRURERUDWHZHUHORDGHGLQORRS$P/DW&$VROXWLRQRIWKHUHTXLUHGDPRXQWRI 3G7)$LQ'0)0H2+ZDVORDGHGLQORRS%P/DW&(DFKZD\ZDVSXPSHG
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
ORDGLQJ 7KH SURFHVV ZDV UHSHDWHG XQWLO UHDFKLQJ WKH WHUPLQDWLRQ FULWHULRQ RI WKH RSWLPL]DWLRQ DOJRULWKP
3URGXFWZDVREWDLQHGDVDPL[WXUHRIGLDVWHUHRPHUV7KH105GDWDDUHFRQVLVWHQWZLWK OLWHUDWXUHSUHFHGHQWD0DMRUGLDVWHUHRPHU+1050+]&'&OįSSPP
+P+GG+- +]W+- +]GG+- +]P+V+GG+- +]GGG+- +]0LQRUGLDVWHUHRPHU +1050+]&'&OįP+ G+- +]W+- +]GG+- +]V+ P+GGG+- +]GGG+- +]&105 0+]&'&OįSSP
Ϯϯ $FNQRZOHGJPHQW 7KLVZRUNZDVVXSSRUWHGE\WKH³5pJLRQGHV3D\VGHOD/RLUH´LQWKHIUDPHZRUNRIWKH³3DULV 6FLHQWLILTXH5pJLRQDX[´'&%JUDWHIXOO\DFNQRZOHGJHWKH³5pJLRQGHV3D\VGHOD/RLUH´IRUD JUDQW);)LVPHPEHURIWKH³,QVWLWXW8QLYHUVLWDLUHGH)UDQFH,8)´ 6XSSRUWLQJ,QIRUPDWLRQ
3UHOLPLQDU\ VLPXODWLRQV RI WKH DOJRULWKP DGGLWLRQDO GHVFULSWLRQV RI WKH VLPSOH[ PHWKRG RSWLPL]DWLRQYDOXHVRIWKHYDULDEOHVIRUDOOH[SHULPHQWV105DQG*&06VSHFWUDRIWKHSURGXFW DUHSURYLGHG 5HIHUHQFHV
D /H\ 6 9 &KHP 5HF E 3URWDVRYD / 1 %XOXW 0 2UPHURG ' %XHNHQKRXGW $ %HUWRQ - 6WHYHQV & 9 2UJ 3URFHVV 5HV 'HY F &KLQQXVDP\7<XGKD66+DJHU0.UHLWPHLHU35HLVHU2&KHP6XV&KHP G1RHO7%XFKZDOG6/&KHP6RF5HYH0F4XDGH'76HHEHUJHU3 +-2UJ&KHPI6LSRV**\ROODL96LSĘF]7'RUPiQ*.RFVLV/ -RQHV5'DUYDV)-)ORZ&KHPJ3ORXIIH30DFFKL$5REHUJH'02UJ 3URFHVV5HV'HYK3RUWD5%HQDJOLD03XJOLVL$2UJ3URFHVV5HV'HY D:HJQHU-&H\ODQ6.LUVFKQLQJ$&KHP&RPPXQE3RHFKODXHU 3&ROEHUJ-)LVKHU(-DQVHQ0-RKQVRQ0'.RHQLJ6*/DZOHU0/DSRUWH7 0DQOH\ - 0DUWLQ % 2¶.HDUQH\0F0XOODQ $ 2UJ 3URFHVV 5HV 'HY F 9DFFDUR / /DQDUL ' 0DUURFFKL $ 6WUDSSDYHFFLD * *UHHQ &KHP G %U]R]RZVNL 0 2¶%ULHQ 0 /H\ 6 9 3RO\]RV $ $FF &KHP 5HV H *XWPDQQ%&DQWLOOR'.DSSH&2$QJHZ&KHP,QW(GI/H\69 )LW]SDWULFN ' ( ,QJKDP 5 - 0\HUV 5 0 $QJHZ &KHP ,QW (G J
Ϯϰ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p--2UJ&KHP
D5DVKHHG0:LUWK7$QJHZ&KHP,QW(GE)DEU\'&6XJLRQR (5XHSLQJ0,VU-&KHPF)DEU\'&6XJLRQR(5XHSLQJ05HDFW
&KHP(QJG6DQV9&URQLQ/&KHP6RF5HYH5HL]PDQ
%--HQVHQ.)$FF&KHP5HV
.ULVKQDGDVDQ 6 %URZQ 5 - & GH0HOOR $ - GH0HOOR - & /DE RQ D &KLS D0F0XOOHQ-3-HQVHQ.)2UJ3URFHVV5HV'HYE0F0XOOHQ- 3 6WRQH 0 7 %XFKZDOG 6 / -HQVHQ . ) $QJHZ &KHP ,QW (G F 0RRUH-6-HQVHQ.)2UJ3URFHVV5HV'HYG5HL]PDQ%--HQVHQ. )&KHP&RPPXQ D%RXUQH5$6NLOWRQ5$3DUURWW$-,UYLQH'-3ROLDNRII02UJ3URFHVV5HV 'HYE3DUURWW$-%RXUQH5$$NLHQ*5,UYLQH'-3ROLDNRII0 $QJHZ &KHP ,QW (G F $PDUD = 6WUHQJ ( 6 6NLOWRQ 5 $ -LQ -
Ϯϱ 6DQV93RUZRO/'UDJRQH9&URQLQ/&KHP6FL )LW]SDWULFN'(%DWWLORFFKLR&/H\692UJ3URFHVV5HV'HY +RXEHQ&3HUHPH]KQH\1=XERY$.RVHN-/DSNLQ$$2UJ3URFHVV5HV'HY D+ROPHV1$NLHQ*5%ODFNHU$-:RRGZDUG5/0HDGRZV5(%RXUQH5 $5HDFW&KHP(QJE+ROPHV1$NLHQ*56DYDJH5-'6WDQHWW\& %D[HQGDOH,5%ODFNHU$-7D\ORU%$:RRGZDUG5/0HDGRZV5(%RXUQH5$ 5HDFW&KHP(QJ
D )HOSLQ ); 1DVVDU+DUG\ / /H &DOORQQHF ) )RXTXHW ( 7HWUDKHGURQ E2JHU1G¶+DOOXLQ0/H*URJQHF()HOSLQ);2UJ3URFHVV5HV'HY
F2JHU1/H*URJQHF()HOSLQ);2UJ&KHP)URQW
D/H&DOORQQHF))RXTXHW()HOSLQ);2UJ/HWWE6XVSHUUHJXL 10LTXHX.6RWLURSRXORV-0/H&DOORQQHF))RXTXHW()HOSLQ);&KHP(XU-
F )HOSLQ);0LTXHX.6RWLURSRXORV-0)RXTXHW( ,EDUJXUHQ2
/DXGLHQ - &KHP (XU - G 2JHU 1 /H&DOORQQHF ) -DFTXHPLQ ' )RXTXHW(/H*URJQHF()HOSLQ);$GY6\QWK&DWDOH2JHU1/H *URJQHF()HOSLQ);&KHP&DW&KHPI.XWRQRYD.97UXVRYD0( 6WDQNHYLFK$93RVWQLNRY36)LOLPRQRY9'%HLOVWHLQ-2UJ&KHP 2JHU1/H*URJQHF()HOSLQ);-2UJ&KHP D7D\ORU-*0RUR$9&RUUHLD&5'(XU-2UJ&KHPE5RJODQV $3OD4XLQWDQD$0RUHQR0DxDV0&KHP5HYF6FKPLGW%(OL]DURY 1 &KHP &RPPXQ G 6FKPLGW % (OL]DURY 1 %HUJHU 5 +|OWHU ) 2UJ
%LRPRO&KHPH6FKPLGW%:ROI)%UXQQHU+(XU-2UJ&KHP
D 2OLYHLUD & & $QJQHV 5 $ &RUUHLD & 5 ' - 2UJ &KHP E 2OLYHLUD&&3IDOW]$&RUUHLD&5'$QJHZ&KHP,QW(G
:HUQHU(:0HL76%XUFNOH$-6LJPDQ066FLHQFH
.KRGMD:/HFODLU$5XOO%DUUXOO-=DPPDWWLR).XWRQRYD.97UXVRYD0( )HOSLQ);5RGULJXH]=XELUL01HZ-&KHP
Ϯϲ D$KPHG%%DUURZ':LUWK7$GY6\QWK&DWDOE$KPHG2PHU %%DUURZ'$:LUWK77HWUDKHGURQ/HWWF1DOLYHOD.67LOOH\0 0F*XLUH0$2UJDQ0*&KHP(XU- D0DOHW6DQ]/0DGU]DN-/H\69%D[HQGDOH,52UJ%LRPRO&KHP E6PLWK&-1LNELQ1/H\69/DQJH+%D[HQGDOH,52UJ%LRPRO&KHP
F 6PLWK & - 6PLWK & ' 1LNELQ 1 /H\ 6 9 %D[HQGDOH , 5 2UJ
%LRPRO&KHPG&KHUQ\DN1%XFKZDOG6/-$P&KHP6RF
H+X';2¶%ULHQ0/H\692UJ/HWWI/L%:LGOLFND' %RXFKHU 6 +D\ZDUG & /XFDV - 0XUUD\ - & 2¶1HLO % 7 3ILVWHUHU ' 6DPS / 9DQ$OVWHQ-;LDQJ<<RXQJ-2UJ3URFHVV5HV'HYJ<X=/Y< <X&2UJ3URFHVV5HV'HYK&KHQ0%XFKZDOG6/$QJHZ&KHP,QW (GL:DQJ;&XQ\*'1RsO7$QJHZ&KHP,QW(G M%KD\D9-RVKL5.XONDUQL$-)ORZ&KHPN6KXNOD&$.XONDUQL$ $5DQDGH995HDFW&KHP(QJ 1HOGHU-$0HDG5&RPSXW-
5DYLQGUDQ $ 5DJVGHOO . 0 5HNODLWLV * 9 (QJLQHHULQJ 2SWLPL]DWLRQ 0HWKRGV DQG
$SSOLFDWLRQV-RKQ:LOH\ 6RQV,QF
.KRGMD:/HFODLU$5XOO%DUUXOO-=DPPDWWLR).XWRQRYD.97UXVRYD0( )HOSLQ);5RGULJXH]=XELUL01HZ-&KHPFQMJ