74 ).20;51 /;),20)4 )+ /; " ##! #'`#!$ MMM FF H= M F HECE = =HJE? AI - 5) - - +)*4-4) 2 +0), -4 6 ) +-.4-50 0 07) / 2 56-4 9 + 56) -; 56-2),4) 21,7+61. ; +)4,1) 15+0-1) + 2)415.1 818 ),1 51 1+ 4-57 65,AF=HJ A JI B*E A@E?= - CE AAHE C 2DOIE CO= @*E FDOIE?I = @2A@E=JHE?I +=IA 9AIJAH 4AIAHLA7 ELAHIEJO + ALA = @ 0 75) 6DEIIJK@OJAIJA@JDAH >KIJ AII B KH? FKJ=JE = @A B O?=H@E= AJ=> EI >O? F=HE CHAIF IAIJ JM @EBBAHA JE FKJIMEJDANFAHE A J= @=J= >J=E A@E FECIK @AHIE E =H? @EJE I )?? H@E C O = =>HKFJ= @=CH=@K= HA@K?JE E? H =HOB M BIE E =H =C EJK@AMAHAE F A A JA@= @KIA@=I @A E FKJ )BJAHB MHA@K?JE IHA=?DA@$BH? JH L= KAI EI?DA E=M=I AFJ? IJ= JB H$ E E > JDCH KFI KHDOF JDAIAIMAHAJD=J JDAIAJM B M HA@K?JE FH BE AIM K @HAIK JE @EBBAHA JJH= IEA JI??A JH=JE I= @B KN H=JAIMDE AD=LE CIE E =HIJA=@O IJ=JAL= KAI= @ KH @A IE K =JA@ HAIF IAIM K @FHA@E?JJDAANFAHE A J= HAIK JIE = = AIJDAJE A@IME A @A B O?=H@E= EI?DA E= 6DAJM @EBBAHA JEI?DA E= E @K?JE F=JJAH IHAIK JA@E JDA I= A@A?HA=IAE IJA=@O IJ=JA 8 = @E IE E =HIJA=@O IJ=JAL= KAIB H AJ=> EJA??A JH=JE I= @B KNH=JAI=J$ E BEI?DA E= 9DE A> JDJDAIE K =JA@= @ ANFAHE A J= HAIK JIID MA@@A?HA=IA@C O? CA??A JH=JE =??K K =JE B =?J=JA = @ AJ =?J=JAHA A=IAMEJDEI?DA E= JDA IAJ BC O? CA @AF AJE = @JDA IMEJ?DJ =?J=JAABB KNMAHA HAH=FE@E JDAANFAHE A JIJD= E JDAIE K =JE I 6DEIIJK@O@A IJH=JAIJDAKJE EJO B? FKJAH @A IB HFHA@E?JE CANFAHE A J= KJ? AIE IJK@EAI B AJ=> E?HACK =JE K @AHFDOIE CE?= = @F=JD CE?=? @EJE I AO9 H@I?=H@E=? AJ=> EI? FKJAHIE K =JE I C O? OIEI DA=HJ =?J=JA 1 64,7+61 O?=H@E= EI?DA E=EIJDAHAIK J B=@A?HA=IAE O?=H@E= > @B M HA =JELAJ JDA H = B MHAGKEHA@J AAJJDA@A = @B H NOCA 6DAHA=HA K AH KI AJ=> E?@AH= CA A JIJD=J=HA=? IAGKA?A BEI?DA E=E? K@E C
# =@A?HA=IAE JDAH=JA B=AH >E?)62IO JDAIEI = E?HA=IAE JDAHA@ NIJ=JA ),0 ), =@A?HA=IAE JDAH=JA BFOHKL=JA= @B=JJO=?E@ NE@=JE = @= IMEJ?DBH AJ =?J=JAKFJ= AJ AJ =?J=JAHA A=IA>OJDA O?=H@EK 6DAANJA J BJDAIA AJ=> E?@AH= CA A JID=I>AA ID M J >A@AFA @A J JDAIALAHEJO JOFA B IAJCH=@K= H=>HKFJ = @@KH=JE BJDAHA@K?JE E B M % 9AHA?A J O@ALA FA@=? FKJ=JE = @A JD=JIE K =JAI?=H@E=? AJ=> EI K @AH H = = @EI?DA E?? @EJE I& 7 E AFHALE KI @A I B?=H@E=? AJ=> EI MDE?DB?KIA@ C O? OIEI= @ HJDA?EJHE?=?E@?O? A= @? IE@AHA@C K? IA=IJDA OA AHCOI KH?A' KH @A E? HF H=JA@ =?AJO + )B H =JE BH JDA NE@=JE B> JD?=H> DO@H=JAIC K? IA= @ =?J=JA= @B=JJO=?E@I KH @A = I E? HF H=JA@IALAH= AO? JH AJ=> EJAI),2 )62 ),0 ), =?AJO + ) = @BHAA + )E J JDA HACK =JE BFOHKL=JA NE@=JE C O? OIEI =?J=JAFH @K?JE JDA?EJHE?=?E@?O? A = @ NE@=JELAFD IFD HO =JE 1 KHFHALE KIF=FAH JDA@ALA F A J BJDA @A MAB K @C @ =CHAA A JMDA MA? F=HA@ @A IE K =JA@HAIK JIMEJDFHALE KI O FK> EIDA@@=J=BH FECI @ CI= @DK = I D MALAHFH IFA?JELAL= E@=JE IJK@EAID=LA J>AA FAHB H A@ 6DKI E JDEIIJK@O KHC = M=IJ JAIJJDA H >KIJ AII B KH @A B O?=H@E= AJ=> EI &>OAL= K=JE CJDA =CHAA A J>AJMAA @A HAIF IAI= @ANFAHE A J= @=J= >J=E A@E KH => K @AHIE E =H? @EJE I )?? H@E C O = =>HKFJIJAF= @=CH=@K= H= F HA@K?JE E B M BIE E =H =C EJK@AMAHAE F A A JA@= @KIA@=I @A E FKJ 6DAH= FHA@K?JE M=IA E?EJA@ LAH=! E FAHE @?AB M HA@K?JE IHA=?DA@$ EI?DA E=M=I =E J=E A@? IJ= JB H$ E KJAIE > JDCH KFI 4AIK JI B @A IE K =JE IBH JDAJM B MHA@K?JE F=JJAH I MAHA? F=HA@J @=J=BH E LEL IME AANFAHE A JI 2HALE KIIJK@EAIID M JD=J=CH=@K= IAJ B O?=H@E= EI?DA E=EI=II?E=JA@MEJD AIIA A@ AJ=> E?@AH= CA A JIMDA? F=HA@J JD IA?=KIA@>O=IK@@A IAJ B EI?DA E= % 9ADOF JDAIE A@JD=JJDAHAIF IAIJ JDAIAB M HA@K?JE FH BE AIME @EIF =O@EBBAHA JJH= IEA JI??A JH=JE = @B KNH=JAI>KJIE E =H IJA=@O IJ=JAL= KAI = @JD=J KH @A IE K =JA@HAIF IAIME FHA@E?JJDA HAIK JI BJDA= E = ANFAHE A JI )6-41) 5), -60,5 @A 5E K =JE I E H @EBE?=JE IJ KHFHALE KI O@ALA FA@ @A &MAHA =@AI JD=JK @AH H = B M? @EJE IJDA??A JH=JE = @B KNL= KAI =J?DA@ KHANFAHE A J= L= KAI? A?JA@ @KHE CJDA EI?DA E?IJA=@OIJ=JA>=IA E AFAHE @6=> AI # 5E K =JE IMAHAJDA FAHB H A@B HJDAJM @EBBAHA JB ME FKJIIJAF= @H= FHA@K?JE IE B M 6DA AJ=> E? IFA?EAI= @HA=?JE IE? K@A@E JDA @A =HA@AFE?JA@E.ECKHA )I= E EJE= L= KAFH > A JDAF=H= AJAHL= KAIE? K@E CE EJE= B KNAIφ λ =N = @ L= KAIMAHAIAJ>=IA@ @=J= BH JDA EI?DA E?IJA=@OIJ=JAFAHE @JD=JMA? A?JA@BH KHE LEL IME AANFAHE A JI
# 6DAE EJE= JEIIKA??A JH=JE L= KAIMAHA= A @A@J HAB A?JJD IA A=IKHA@ANFAHE A J= O 6=> A 6DAKF@=JA@F=H= AJAHI=HA EIJA@E 6=> AI # 2=HJEJE? ABBE?EA JIMAHAAIJE =JA@ BH E EJE= IJK@OIJ=JAL= KAIB H=HJAHE= LA KI= @JEIIKA??A JH=JE I= @JDAH=JA B AJ KFJ= A HHA A=IA& 6DA =JDA =JE?= HAFHAIA J=JE BJDA @A EI=IAJ B@EBBAHA JE= = @ = CA>H=E?AGK=JE IJD=JB H = E EJE= L= KAFH > A 6DA @A M=I? @A@E. 464) = @ JDAAGK=JE IMAHAI LA@KIE C 5,-5 = E F E?EJE JACH=J H@ALA FA@>O0E @ =HID= @ @AIEC A@AIFA?E= OB HIJEBB= @IF=HIAIOIJA I 6DA 5,-5I BJM=HAEI=L=E => AB H@ M =@ =JDJJF MMM AJ E> HC = E= J @A FH C I @AI B ) E = 2HAF=H=JE -NFAHE A JIMAHAFAHB H A@ $@ AIJE?FECI A= MAECDJ!% C 6DAIAIJK@EAI MAHA? @K?JA@E =?? H@=?AMEJDJDA/KE@AB HJDA+=HA= @7IA B => H=J HO) E = I 10 2K> E?=JE K >AH&#!= @JDA1 IJEJKJE = ) E = +=HA= @7IA+ EJJAA=J+=IA9AIJAH 4AIAHLA7 ELAHIEJO 9AKIA@=FHALE KI O@ALA FA@ FA?DAIJ @A JD=J= MIB HIE K J= A KI A=IKHA A JI B O?=H@E= IK>IJH=JAKJE E =JE C K? IA =?J=JA = @B=JJO=?E@I AJ=> EJA??A JH=JE IE =HJAHE= = @? H =HOLA KI> @ = @JEIIKAIK>IJH=JA??A JH=JE I #. ME C= LAH ECDJB=IJ = E = IMAHAIA@=JA@MEJD$ C C B6A = E CELA EI B KH= A#>O KJD Glycogen Glucose Glucose-6-Phosphate O 2 ATP ADP NAD + ADP Lactate NADH ATP Pyruvate NADH NAD + ETC ATP ADP NAD + H 2 O NADH Fatty Acid Acetyl-CoA ATP PC NAD + ADP Cr NADH CO 2.ECKHA 5?DA =JE?@AFE?JE BJDA AJ=> E?HA=?JE IE? HF H=JA@E JDA? FKJ=JE = @A
# 6=> A 1 EJE= +?A JH=JE I 6EIIKA +?A JH=JE C 4ABAHA?A / '.) ' /2 % /;!! ' 6/! " 2; )! && )+ "$ ".+ && " + )2 "! " '$!!# +!# ), " ),2 " 2+ & &! ),0 "# )62!!& )HJAHE= +?A JH=JE 4ABAHA?A / " '.) # ' ) & #! %%! + &!,A JAI@=J=BH FHAIA JIJK@O )>>HALE=JE I / C K? IA.) B=JJO=?E@I /2 C K? IA$ FD IFD=JA /; C O? CA 6/ JHEC O?AHE@A 2; FOHKL=JA ) =?J=JA )+ =?AJO + ).+ BHAA + ) + )2 J J= + )F ), NE@E A@ E? JE = E@A=@A E A@E K? A JE@A 2+ FD IFD?HA=JE A ),0 HA@K?A@ E? JE = E@A=@A E A@E K? A JE@A 6=> A * @ 6EIIKA2=HJEJE + ABBE?EA JI 2=HJEJE + ABBE?EA J 8= KA 4ABAHA?A I/! $& I.) %" I2; $'# % I )!&,A JAI@=J=BH FHAIA JIJK@O E JK>=JA@LE=JH=?DA J O =E J=E A@MEJDEI B KH= A %# #= @ AJ= E A" C C DH = @LA JE =JA@J =E J=E > @C=IAIE JDA H = H= CA2 0C 2+!# "# 0C = @F0%!# % "#" 6DADA=HJM=IANF IA@LE== E@ E AIJAH J OMEJD= ABJ IE@AHE> HAIA?JE = @IKIFA @A@E =FAHE?=H@E= I E C )BA H= LAE M=I?= K =JA@JDH KCDMDE?D DAF=HE M=IE BKIA@J FHALA J? JJE C 7 C> KI B MA@>O#7 C DHE L = @= JHEC O?AHE@AA K IE 1 JH= EFE@! C DHELMAHAE BKIA@J H=EIA?EH?K =JE CBHAAB=JJO =?E@I..)J DK = ALA I $ )BA H= =HJAHOM=I?= K =JA@= @KIA@J FHE AJDA FAHBKIE E AKIE C=H AHFK F 6DA ABJ= JAHE H@AI?A @E C? H =HO=HJAHO ),M=I?= K =JA@=> LAJDABEHIJ@E=C = >H=?D= @FAHBKIA@MEJD> @IKFF EA@BH JDABA H= =HJAHO
#! 6=> A! 1 EJE=. KNAI CMAJMJ E. KN. KN8= KA 4ABAHA?A φ / /2 " ' φ.) 6/ $!" φ.) )+ " φ /2 2; " ' φ /2 /; ' φ /; /2 ' φ 6/.)!" φ 2; ) $ φ 2; )+ %! φ ) 2; # φ )+ + $ φ 0 & φ +4 2+ φ 2+ +4 φ )+ + )2! φ + )2.+! φ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
# # 120 STEP PROTOCOL LAD Blood Flow (% of normal control flow) 100 80 60 40 20 0 120-20 0 20 40 60 Time (min) RAMP PROTOCOL LAD Blood Flow (% of normal control flow) 100 80 60 40 20 0-60 -40-20 0 20 40 60 Time (min).eckha 5JK@OFH J? I )2H J? B HIJAF HA@K?JE E B M * 2H J? B HH= FHA@K?JE E > @B M * @F =I = I= F AI + LE= I = @ I=JKH=JA@I= E?O E?=?E@ 55)I= F AIMAHA? A?JA@=JIEN@EBBAHA J > @I= F AJE AF E JI " + C K? IA = @ " + =?J=JA??A JH=JE IMAHAE A@E=JA O@AFH JAE E A@E E?A? @ FAH?D HE?=?E@ L L 6DAOMAHAJDA = = O A@B HC K? IA= @ =?J=JAKIE CA O =JE? IFA?JH FD J AJHE?=II=OI! # 6DAIFA?EBE?H=@E =?JELEJO B " + C K? IAM=I A=IKHA@ @AFH JAE E A@> @I= F AIKIE CE AN?D= CAHAIE?DH =J CH=FDO= @> @ " +??A JH=JE M=I=IIAIIA@>OJH=FFE CEJE DO= E ADO@H NE@A =IFHALE KI O@AI?HE>A@' 2 =I =B=JJO=?E@= @! 0 A=JA??A JH=JE IMAHA A=IKHA@=IFHALE KI O@AI?HE>A@!! 0 M=I A=IKHA@>O@AJAH E E CJDA@EBBAHA?AE @F BM=JAH@EIJE A@BH F =I =KIE C =0E? = IJE JAI/ =II +KIJ 5D F " 6DAA HE?D A J B =?J=JAMEJD! + =?J=JAM=I A=IKHA@E F =I =@AFH JAE E A@MEJDI= E?O E?=?E@KIE C/+ 5= = OIEI BJDAJAHJ >KJO @E AJDO IE O 6*, 5@AHEL=JELA=IFHALE KI O@AI?HE>A@ #
# $ 6DAJEIIKA>E FIEAIJ= A @KHE CJDAE EJE= IJ=JA= @=BJAH% E # E = @$ E BJDA$ HA@K?JE E B MMAHAKIA@J A=IKHAJDAJEIIKA ALA I B)62 ),2 C O? CA = @ =?J=JA 6EIIKA ALA I B)62= @),2MAHA A=IKHA@ K E AJHE?= O>O AJD @IFHALE KI O@AI?HE>A@ $ 6EIIKAC O? CA M=I A=IKHA@MEJDFAH?D HE?=?E@ANJH=?JIKIE CJDA= O C K? IE@=IA AJD @>O AJD @IFHALE KI O@AI?HE>A@ % 6EIIKA =?J=JA A=IKHA A JIMAHA? F AJA@MEJD= A O =JE? IFA?JH B K H AJHE?=II=O KIE C @EBEA@JA?D EGKAIE E =HJ JD=J BJDA> @ =?J=JA=II=O 6DA! CH= FK?D>E FIOJ= A =JJDA?? KIE BA=?DANFAHE A JM=IKIA@J A=IKHA ), = @ JHEC O?AHE@A ALA I 6EIIKAM=IANJH=?JA@E E?A? @?D H B H AJD= L L = @ JHEC O?AHE@A ALA IMAHA A=IKHA@KIE C= A O =JE?IFA?JH FD J AJHE?=II=O6HEC O?AHE@A- EJ 9= +DA E?= I 4E?D @ 8) ), M=I A=IKHA@IFA?JH FD J AJHE?= OKIE C=FHALE KI O @AI?HE>A@ AJD @ & +=?K =JE I 6DA AJKFJ= AI CMAJMAECDJ E B HC K? IA =?J=JA = @BHAAB=JJO=?E@IMAHA?=?K =JA@>=IA@ JDAFH @K?J BJDA=HJAHE= = @? H =HOLA KIIK>IJH=JA@EBBAHA?A= @JDA H = E A@ O?=H@E= > @B M CMAJMAECDJ E 6DAH=JAI BAN CA KIC K? IA= @ B=JJO=?E@ NE@=JE MAHA?=?K =JA@=IJDAFH @K?J BJDAHA A=IA BAEJDAH " + H! 0 @F = @ H = E A@ O?=H@E= > @B M @ELE@A@>OJDA=HJAHE= IFA?EBE?H=@E =?JELEJO BC K? IA H BHAAB=JJO=?E@I@F! 5E K J= A KI =?J=JAKFJ= A= @HA A=IAMAHA?=?K =JA@BH JDA! + =?J=JAA HE?D A J= @> @ =?J=JA??A JH=JE I=IFHALE KI O@AI?HE>A@ 6DAH=JAI BC K? IA= @B=JJO=?E@KFJ= A= @ NE@=JE = @JDAH=JAI B =?J=JAKFJ= A= @FH @K?JE MAHA KIA@E @AJAH E E CJDAE EJE= B KNL= KAI6=> A! O?=H@E= > @B MM=I A=IKHA@BH JDA?= E>H=JA@FK FB M BJDAFAHBKIE?EH?KEJ= @ H = E A@>O@ELE@E C>OJDAMAECDJ BJDADA=HJ >AE CFAHBKIA@>OJDA ),% 6DA 82 IAC A J A CJD F=HA=M=I?=?K =JA@ BB E ABH =FFH NE =JA O!? IA?KJELA DA=HJ>A=JI>OKIE CI BJM=HA@ALA FA@E =J => 6DEIM=IKIA@=I= E @AN BJDAANJAH = M H BJDA= JAHE HBHAAM= BJDA ABJLA JHE? A= @M=IANFHAIIA@=I=BH=?JE BJDAE EJE= IJ=JA L= KAI 6DA 82 IAC A J A CJD F=HA= K JEF EA@>OJDADA=HJH=JAM=IKIA@=I= E @AN BJDA ANJAH = F MAH BJDA= JAHE HM= 5J=JEIJE?= ) = OIEI 6HEC O?AHE@A = @ ),??A JH=JE IMAHA? F=HA@>AJMAA JDA ),= @?EH?K B AN+.:? JH >A@= @>AJMAA IJAF= @H= FCH KFIKIE C=JM M=O= = OIEI BL=HE=?A 7FJ= AI B C K? IA =?J=JA = @BHAAB=JJO=?E@ = DA @O = E?F=H= AJAHI HACE = = JAHE HM= M H = @ F MAHE @E?AI = @C O? CA = @)62??A JH=JE MAHA? F=HA@KIE C=JM M=OHAFA=JA@ A=IKHA= = OIEI BL=HE=?A KIE C=5JK@A J AM = AK IJAIJB HF IJD?? F=HEI I ) JAIJIB HIEC EBE?=?AMAHAFAHB H A@=JJDA # ALA BIEC EBE?=?A= @= L= KAI=HAHAF HJA@=I A= I 5-4-57 65 5E K =JE 4AIK JI= @-NFAHE A J=,=J= 4= FEI?DA E=M=IE @K?A@>O@A?HA=IE CB MBH J " %$ " C E J! C E B H =? H =HO> @B ME = E A=H = AH LAH! E MDE AIJAFEI?DA E=M=IE @K?A@>O@A?HA=IE CJDA
# % B MJDAI= A =C EJK@A %! # C E J ' C E LAH E 6 JAIJJDAH >KIJ AII B KH? FKJ=JE = @A MEJDKF@=JA@ E EJE=? @EJE I= @F=H= AJAHL= KAI MA? F=HA@JDA??A JH=JE I= @ B KNH=JAIJD=JMAHA A=IKHA@ANFAHE A J= OMEJDJDA? HHAIF @E C @A IE K =JA@HAIK JI 9EJDJDAE JH @K?JE BEI?DA E= JDAHAM=I= E A@E=JA@A?HA=IAE O?=H@E= NOCA? IK FJE 8.ECKHA!)= @=FH F HJE =JA @A?HA=IAE )62.ECKHA!* 6DA @A IE K =JE IB H> JDJDAIJAF= @H= F ID M=#@A?HA=IAE 8 MDE AANFAHE A J= OJDA@A?HA=IAIMAHA#" = @#& HAIFA?JELA O6=> A$ 6DAIAHAIK JIID MJD=JJDAJM @EBBAHA JB MHA@K?JE FH BE AIHAIK JE IE E =HIJA=@O IJ=JA@A?HA=IAIE 8 6DA@A?HA=IAIE )62B HIJAFMAHA"= @"B HANFAHE A J= = @ IE K =JA@ HAIFA?JELA O MDE AJD IAB HH= FEI?DA E=MAHA$'= @" 6=> A$ 0A @O = E?L= KAIBH E LEL IME AANFAHE A JI Ramp Reduction in Blood Flow 60% Reduction in Blood Flow HR (beats/ min) Baseline -15-5 6 30 60 Step 111 ± 3.3 113 ± 5.5 120 ± 9.3 112 ± 6.3 Ramp 115 ± 4.8 118 ± 9.3 119 ± 9.9 114 ± 7.1 119 ± 8.5 127 ± 9.4 Peak LVP (mm Hg) Step 88 ± 3.4 83 ± 4.7* 80 ± 5.2* 79 ± 4.1* Ramp 87 ± 2.0 82 ± 2.5 79 ± 4.6 80 ± 5.4* 79 ± 5.2* 75 ± 3.5* dp/dt max (mm Hg/s) Step 2341 ± 105 2014 ± 132 2008 ± 137 2101 ± 175 Ramp 2503 ± 212 2453 ± 211 2065 ± 104 2052 ± 154 2180 ± 239 2032 ± 149 dp/dt min (mm Hg/s) Step -1978 ± 137-1764 ± 211-1628 ± 178-1548 ± 141 Ramp -2101 ± 114-1733 ± 89-1481 ± 64-1638 ± 159-1530 ± 109-1482 ± 73 MVO 2 (µmol/g/min) Step 2.43 ± 0.11 1.12 ± 0.08* 0.95 ± 0.09* 0.88 ± 0.06* Ramp 2.75 ± 0.12 2.51 ± 0.26 1.58 ± 0.14 1.14 ± 0.09* 1.09 ± 0.13* 1.03 ± 0.09* Work (mm Hg mm) Step 1.00 0.65 ± 0.11 0.65 ± 0.15 0.56 ± 0.12* Ramp 1.00 0.84 ± 0.10 0.64 ± 0.10 0.56 ± 0.11 0.45 ± 0.12 0.35 ± 0.12* Power (mm Hg mm/s) Step 1.00 0.68 ± 0.12 0.69 ± 0.16 0.61 ± 0.15 Ramp 1.00 0.83 ± 0.08 0.62 ± 0.08 0.53 ± 0.09 0.43 ± 0.10 0.37 ± 0.13 8= KAI=HA A= I 5-MEJD%FECIE JDAH= FCH KF= @'FECIE JDAIJAFCH KF 04 DA=HJH=JA @2 @J BEHIJ@AHEL=JELA BFHAIIKHA 82 ABJLA JHE?K =HFHAIIKHA 8 O?=H@E=? IK FJE 9 H = @F MAH=HAANFHAIIA@=IJDABH=?JE BJDA>=IA E AL= KA 2 #? F=HA@J >=IA E A
# &.ECKHA! O?=H@E= NOCA? IK FJE 8 )= @)62??A JH=JE?D= CAI*,=IDA@ E AIHAFHAIA J @A IE K =JA@HAIF IAIBH H= FE @K?JE BEI?DA E=MDE AI E@ E AIHAFHAIA JHAIF IAIBH IJAFE @K?JE BEI?DA E= 6DA FA?EH? AIHAFHAIA JANFAHE A J= @=J=BH JDAIJAFCH KFMEJDJDABE A@?EH? AIHAFHAIA JANFAHE A J= @=J=BH JDAH= FCH KF F #>AJMAA JDAIJAFLI H= FCH KFI
# ' ) JDAH? IAGKA?A BEI?DA E=EI= =??A AH=JE BC O? OIEIJD=JHAIK JI E E?HA=IA@KJE E =JE BC O? CA =??K K =JE B =?J=JAE JDADA=HJ = @= IMEJ?DBH AJ =?J=JAKFJ= AJ AJ =?J=JAHA A=IA>OJDADA=HJ 1 JDAIJAFCH KF C O? CA? JA J@A?HA=IA@ =BJAH$ E KJAI BEI?DA E= >O&! "E JDA = E = ANFAHE A JI= @>O%$E JDAIE K =JE I.ECKHA") 1 JDAH= F CH KF C O? CA? JA J@A?HA=IA@>O&!!E JDAANFAHE A JIMDE AJDA @A FHA@E?JA@= &&@A?HA=IA.ECKHA") -LA JD KCDJDAIJA=@O IJ=JA C O? CA??A JH=JE L= KAIMAHAIE E =HE = B KH?=IAIIJAFLI H= F= @ ANFAHE A JILI IE K =JE I=BJAH$ E KJAI BEI?DA E= JDAJH= IEA J>AD=LE H M=I@EBBAHA JMDA ANFAHE A JIMAHA? F=HA@J? FKJAHIE K =JE I -NFAHE A J= O C O? CA??A JH=JE @A?HA=IA@E =DOFAH> E? HANF A JE= = AHMDE AJDA @A FHA@E?JA@= E A=H@A?HA=IAE C O? CA??A JH=JE HAC=H@ AII BB M HA@K?JE F=JJAH 6DKI JDAANFAHE A J= H=JA BC O? CA KJE E =JE E?HA=IA@ HAH=FE@ OE EJE= O= @J=FAHA@ BBGKE? AHJD= JD=J FHA@E?JA@>OJDA? FKJAH @A.ECKHA") =?J=JA=??K K =JE = @JDAIMEJ?DBH AJKFJ= AJ AJHA A=IA B =?J=JA >OJDADA=HJHAIK JIBH JDAE?HA=IA@H=JA BC O? OIEI >IAHLA@@KHE C EI?DA E= 6DA @A IE K =JA@HAIK JIB HJEIIKA =?J=JABEJMEJDE JDAIJ= @=H@ AHH H>=HI BJDA A=IKHA@??A JH=JE I = @E?HA=IA@JM J JDHAAB @=> LA E EJE= L= KAIE > JDCH KFI.ECKHA"* )IM=IJDA?=IAMEJDC O? CA >HA= @ M JDA @A IE K =JA@JE A? KHIA B =?J=JA=??K K =JE J =IJAF HA@K?JE E > @B MM=II MAHJD= IAA ANFAHE A J= O 6DA @A IE K =JA@HAIK JIID MA@=@A =OE JDAIMEJ?DBH AJ =?J=JAKFJ= AJ AJ HA A=IA = @=CHA=JAHH=JA B =?J=JAHA A=IABH J $ E KJAI BEI?DA E=? F=HA@J JDAANFAHE A J= @=J=.ECKHA# 9DE A> JDJDAIE K =JA@= @ ANFAHE A J= HAIK JIID MA@@A?HA=IA@C O? CA??A JH=JE =??K K =JE B =?J=JA = @ AJ =?J=JAHA A=IAMEJDEI?DA E= JDA IAJ BJDAH=JA BE?HA=IA B C O? CA OIEI= @JDAIMEJ?DJ =?J=JAABB KN??KHHA@I AH= @ HAH=FE@ O E JDAANFAHE A JIJD= E JDAIE K =JE I 6DKI JDAANFAHE A J= H=JA B C O? CA KJE E =JE = @ =?J=JAFH @K?JE E?HA=IA@ HAH=FE@ OE EJE= O= @ J=FAHA@ BBGKE? AHJD= JD=JFHA@E?JA@>OJDA? FKJAH @A = O?D= CAIE @K?A@>OEI?DA E= E? K@E CJDAE?HA=IA@H=JA BC O? OIEI = @@A?HA=IA@H=JAI B NOCA? IK FJE = @A A?JH JH= IF HJ?D=E B KN HAIK JE =@A?HA=IAE JDA??A JH=JE B ), = @= E?HA=IAE JDAHA@ N IJ=JA ),0 ), 6DA O?=H@E= ),? JA JIMAHA " = @!' I CE JDA EI?DA E?+.:FAHBKIE JAHHEJ HOB HJDAIJAF= @ H= FCH KFI HAIFA?JELA O = @JDAOMAHAHA@K?A@>O "= @ # $ E JDAEI?DA E? ),JAHHEJ HO 6DA @A IE K =JE HAIK JIFHA@E?JA@@A?HA=IAI MAHA"= @""B HIJAF= @H= F HAIFA?JELA O MDE?DB MA@=JE A? KHIA IE E =HJ 8 6DAANFAHE A J= HAIK JI= @JDA @A IE K =JA@HAIK JI> JD ID M=@A?HA=IAE JDA??A JH=JE B ), = @JDA @A FHA@E?JI=IALA B @E?HA=IAE JDAHA@ NH=JE
#!.ECKHA" / O? CA )= @ =?J=JA*??A JH=JE?D= CAI,=IDA@ E AIHAFHAIA J @A IE K =JA@HAIF IAIBH H= FE @K?JE BEI?DA E=MDE AI E@ E AIHAFHAIA JHAIF IAIBH IJAFE @K?JE BEI?DA E= 6DA FA?EH? AIHAFHAIA JANFAHE A J= @=J=BH JDAIJAFCH KFMEJD JDABE A@?EH? AIHAFHAIA JANFAHE A J= @=J=BH JDAH= FCH KF
#!.ECKHA# AJ =?J=JAKFJ= A>OJDADA=HJ 6DAF IEJELAL= KAIHAFHAIA J AJ =?J=JAKFJ= AMDE AJDA AC=JELAL= KAIID M AJ =?J=JAHA A=IA>OJDADA=HJ 6DAFA= =?J=JAHA A=IA>OJDADA=HJM=I IEC EBE?= J O@EBBAHA J>AJMAA JDAIJAF= @H= FCH KFIF # + F=HEI B5JAF= @4= F 8= KAIB HJDA A=IKHA@DA @O = E?L=HE=> AI=HAFHAIA JA@E 6=> A$ 6DAHAMAHA IEC EBE?= J@EBBAHA?AI>AJMAA JDAIJAF= @H= FCH KFI HAC=H@E C= O BJDAIAL= KAI 2A= ABJLA JHE?K =HFHAIIKHA 82B H> JD CH KFI? >E A@M=IIEC EBE?= J ODECDAH=J>=IA E AJD= =J= OJE AF E J @KHE CJDA$ E B$HA@K?JE E > @B M 0 MALAH 82L= KAIMAHA J IEC EBE?= J O@EBBAHA JBH A=?D JDAH>AO @$ E 6=> A$ 9 H = @F MAH =J$ E MAHAIEC EBE?= J O@EBBAHA JBH JD IA=J$ E O?=H@E= NOCA? IK FJE M=IIEC EBE?= J O@EBBAHA J>AJMAA >=IA E AL= KAI= @L= KAI @KHE CJDA$HA@K?JE E > @B M 2A= =?J=JAHA A=IAM=ICHA=JAHE JDAIJAFCH KF ' C E JD= E JDAH= FCH KF $' C E 2 # 0 MALAH @EBBAHA?AM=I IAA >AJMAA JDACH KFIE JEIIKA =?J=JA??A JH=JE =?J=JAFH @K?JE = @ IJA=@O IJ=JA =?J=JAHA A=IA=JJDAA @ BJDA$ E B$HA@K?JE E > @B M 6DAJEIIKA)62??A JH=JE M=I MAHE JDAH= FCH KF2 # 6DAHAM=I @EBBAHA?AE C K? IA NE@=JE B=JJO=?E@ NE@=JE C O? CA??A JH=JE H = O BJDA JDAH A=IKHA@IFA?EAI??A JH=JE I HB KNAI
#!,15+7551 9AFHALE KI OFHAIA JA@ @A IE K =JE IB H$ E =J=$HA@K?JE E > @B M= @L= E@=JA@JDAIE K =JE IMEJDHAJH IFA?JELAANFAHE A J= @=J=& 1 JDAFHAIA JIJK@O MAFH IFA?JELA O? F=HA@ @A IE K =JA@= @ ANFAHE A J= HAIK JIBH JM @EBBAHA JB M HA@K?JE FH BE AI ID ME CJDA H >KIJ AII= @ E EJ=JE I BJDA @A 6DAJM @EBBAHA JE @K?JE F=JJAH I B $EI?DA E=HAIK JA@E JDAI= A@A?HA=IAE IJA=@O IJ=JA 8 = @E IE E =H IJA=@O IJ=JAL= KAIB H AJ=> EJA??A JH=JE I= @B KNAI @A IE K =JE I E HAIF IAJ IJAF= @H= F> @B MHA@K?JE I=CHAA@MA MEJDI A BJDA ANFAHE A J= @=J=A C =?J=JA??A JH=JE BE = C O? CA??A JH=JE MDE A I A BJDAHAIK JID=@@EBBAHA J?D= CAIE =C EJK@A= @JE A? KHIAIA C 8 =?J=JAHA A=IA C O? CA @AF AJE 9AD=LA@ALA FA@JDABEHIJ? FKJ=JE = @A B O?=H@E= A AHCO AJ=> EI JD=JE? HF H=JAIJDA AO?=H> IK>IJH=JAI BDK = O?=H@E= AJ=> EI 1 JDEIIJK@OMAJAIJA@JDA @A MEJDJM @EBBAHA JE @K?JE I B EI?DA E=. H> JDB MHA@K?JE IKIA@ KH @A IE K =JA@HAIK JI=CHAA@ HA =JELA OMA MEJDJDAANFAHE A J= @=J=MA? A?JA@BH JDA? HHAIF @E CE LEL = E = IJK@EAI= @ JDAHFHALE KI OFK> EIDA@@=J= 6DAJE A? KHIAIB HJDA @A?HA=IAIE 8 )62 ), = @C O? CA @EBBAHA@>AJMAA JDAIJAF= @ H= FCH KFI= JD KCDJDAEH A=IKHA@= @ @A IE K =JA@IJA=@O IJ=JAL= KAI MAHAIE E =H 6DAI= AHA =JE IDEFIDA @B HJDA=??K K =JE B =?J=JA= @JDA IMEJ?DBH AJ =?J=JAKFJ= AJ AJHA A=IA 9AIA A?JA@JDAJM @EBBAHA JB M HA@K?JE FH BE AIE H@AHJ ID MJDA =>E EJO BJDA @A J =??KH=JA OFHA@E?J?D= CAI??KHHE CBH > JDB M HA@K?JE IKIE C=IE C AIAJ BF=H= AJAHL= KAI 6DAIJAFB M HA@K?JE FH BE A M=IIA A?JA@>A?=KIAEJEIJDA IJ? OKIA@ AJD @ BB M HA@K?JE E ANFAHE A J= IJK@EAI BEI?DA E= = @EJHAIK JIE =H=FE@HA@K?JE E 8 NE@=JELAFD IFD HO =JE = @=?JEL=JE BC O? OIEI 1 =@@EJE FHALE KI IJK@EAIID MA@JD=JJDAH= FB MHA@K?JE FH BE AHAIK JIE AII=?JEL=JE B C O? OIEI % )IIAA E.ECKHA!) JDAHAIK JI=CHAA@MEJD KHDOF JDAIEI JD=JJDAJM AJD @I B> @B MHA@K?JE HAIK JE IE E =H@A?HA=IAIE 8 = JD KCDMEJD@EBBAHA JJE A? KHIAI 6DAANFAHE A J= HAIK JI##= @#& @A?HA=IAIE 8 B HIJAF= @H= F HAIFA?JELA OID MA@= =HCAH@A?HA=IAJD= FHA@E?JA@>OJDA @A # 6DAE EJE= ANFAHE A J= 8 L= KAI $= @ & CMAJMJB HIJAF= @H= F HAIFA?JELA OBH KH?KHHA JIJK@OMAHA IK>IJ= JE= O MAHJD= FHALE KI OFK> EIDA@ANFAHE A J= L= KAI MDE?DH= CA@ BH % #J # CMAJMJ E MEJD= =LAH=CA B" & CMAJMJ E = @ = A@E= L= KA B" % CMAJMJ E # %! % '!! 6DHAAFHALE KI IJK@EAIE L LE C=$HA@K?JE E > @B MHAIK JA@E "$ "' = @# @A?HA=IAIE 8 @KAJ EI?DA E=# $!! KH @A IE K =JA@HAIK JI MEJD=#HA@K?JE E 8 =HA? F=H=> AMEJDJDAIAFHALE KIHAIK JI
#!! ) JDAH@EBBAHA?A>AJMAA KHANFAHE A J= @=J== @FK> EIDA@@=J=BH JDAHE LEL FECIJK@EAIEIJDA>=IA E A> @B ML= KAI 6DAH= CA B H = > @B ML= KAIHAF HJA@H= CA@BH %J "! C E # %! %!!#= @ KHANFAHE A J= > @B MM=I %!= @ %$ C E B HIJAF= @ H= FCH KFI HAIFA?JELA O ) JD KCD KH A=IKHA@ANFAHE A J= L= KAIB H 8 = @> @B M=HA MAHJD= I AFK> EIDA@L= KAIMEJDIE E =HFHAFI JDAIA?KHHA JL= KAI=CHAAMEJDJD IAHA?A J OFK> EIDA@KIE CJDAI= AFHAF=H=JE '.KHJDAH HA @KHE CJDAIAANFAHE A JIJDAIME AMAHA JEI?DA E? H IJHAIIA@@KHE CJDAE EJE= IJ=JA =IALE@A?A@>OJDA =? B AJ =?J=JAFH @K?JE JDAHA =JELA O MDA=HJH=JAI = @IJ=> A 8FHAIIKHAI 6DA??A JH=JE B ), EIANFA?JA@J @A?HA=IAMEJD= E?HA=IAE ),0??A JH=JE @KHE CEI?DA E= 7 B HJK =JA O JDAHAEI E EJA@@=J==L=E => A JDA??A JH=JE I B ), = @ ),0@KAJ JDA@EBBE?K JO B A=IKHE CJDA KH @A IE K =JA@HAIK JIHAB A?JJDAIA?D= CAI= @MA=JJA FJA@J A=IKHA JDA > JDKIE CJDAJAH E = FK?D>E FIEAI? A?JA@@KHE CJDAANFAHE A JI 6DA A=IKHA@@A?HA=IAIE ), MAHA AIIJD= JD IAFHA@E?JA@>OJDA @A = @ JDAHAM=I @EBBAHA?A>AJMAA JDAIJAF= @H= FCH KFI 1 H@AHJ IAJJDA E EJE=??A JH=JE L= KAB H ),0E JDA @A MAKIA@=>=IA E AH=JE B H ),0J ), BH FHALE KI OFK> EIDA@L= KAI 6=> A!$!%= @ KH A=IKHA@ ), L= KAIJ?=?K =JAJDA? HHAIF @E C ),0??A JH=JE ) JD KCD KH A=IKHA A JI B ), FH LE@AKIABK E IECDJE J JDAF IIE> A?D= CAIE JDAFOHE@E A K? A JE@AF MEJDJDAE JH @K?JE BEI?DA E= JDA =? B JDAHANFAHE A J= @=J=E JDA=HA= = AIEJ@EBBE?K JJ @H=M? A=H?? KIE I BH KH@=J= 9DE AJDAIJA=@O IJ=JAANFAHE A J= L= KAIB HJEIIKAC O? CA = @ =?J=JA? JA J=J$ E KJAI BEI?DA E==CHAA@HA=I => OMA MEJDIE K =JA@HAIK JI JDA @A IE K =JA@JE A? KHIAI@KHE CJDAJH= IEJE J $EI?DA E= =CCA@ >ADE @B H> JD AJ=> EJAI 5FA?EBE?= O JDA @A @E@ JFHA@E?JJDAH=FE@>KHIJ E C O? CA @AF AJE = @ =?J=JAFH @K?JE @KHE CJDAE EJE= E KJAI BEI?DA E= HJDA@A? E ABH #J $ E 1 JDEI?=IA ANFAHE A J= @=J=IKCCAIJIJDA @A? F A JIJD=J AA@J >AHALEIA@>OE? HF H=JE C HA>E?DA E?= @AJ=E H? JH A?D= EI IA C HA=?JE I H? JH AHI 6DEI? K @ A=@J = >AJJAH? HHAIF @A?A>AJMAA @A IE K =JE I= @ANFAHE A J= HAIK JI@KHE C JDA@O = E?FD=IA BJDAHAIF IA 0 MALAH IE?A KI? A>E FIEAIJ A=IKHA C O? CA? JA JE JDA O?=H@EK =HA@EBBE?K JJ J= ABHAGKA J O JDAH AJD @I B @A L= E@=JE AA@J >AE F A A JA@J FH LE@AA KCDE LEL @=J=J @AI?HE>AJDAJE A? KHIA BC O? CA @AF AJE 6DAI KCCEID AII BI A BJDA HAIF IAI E A O??KHI>A?=KIA M? JH AHI BC O? CA OIEI= @ C O? OIEI=HA EIIE CE JDA?KHHA J @A 6DA=@@EJE BE HC= E?FD IFD=JA 2 E?OJ I E?+= = @JDA=@A E A K? A JE@AI) 2 =@A IE A 1 2 E IE A MDE?D? JH AOHACK =J HOA O AIE JDAIAF=JDM=OI ID K @DA FIFAA@KF JDAIAJE A? KHIAI 6DAO=HA JE? K@A@E JDA @A @KAJ =? BHA E=> A@=J= = @= = OJE?= A=IKHA A JI=FF E?=> AJ KHE LEL ANFAHE A J= FHAF=H=JE 1
#!" H@AHJ =??KH=JA O @A JDAHAIF IAI B2 E += = @=@A E A AJ=> EJAIEJ M K @>A A?AII=HOJ E?HA=IAJDA? F ANEJO BJDAHA=?JE IE? K@A@JDA @A = @J >J=E I AHA= EIJE?ANFAHE A J= L= KAI 1 =@@EJE KH @A @ AI J IAF=H=JAJDA?OJ I E?? F=HJ A JBH JDA EJ?D @HE= =@@EJE B=?OJ I E?? F=HJ A JM K @E?HA=IAJDAIA IEJELEJO BC O? OIEIJ HACK =J HO AJ=> EJAI E JDA?OJ I + HJ=II=AJ= HA?A J O@ALA FA@= E JACH=JA@JDAH E AJE? @A @AI?HE>E C? JH B?=H@E=? EJ?D @HE= >E A AHCAJE?I = @@A IJH=JA@JDA E F HJ=?A B EJ?D @HE= =JHEN+= E =J?DE CA AHCOIKFF OMEJD@A = @ E?=H@E=? O?OJAI!& 9DE AJDEIE F HJ= J @A EILAHOKIABK B H K @AHIJ= @E C?=H@E=? EJ?D @HE= BK?JE EJ@ AI JE? K@AC O? OIEI H B=JJO=?E@ NE@=JE = @EJ?= J>A@EHA?J O=FF EA@J E LEL? @EJE I + A=H O BKJKHA @A @ALA F A J= @IK>IAGKA JL= E@=JE IJK@EAIID K @=E J E? HF H=JAJDAIA AO AJ=> EJAI= @ K JEF A?A? F=HJ A JI 1 IK =HO MAFHAIA J=? FKJ=JE = @A BDK = E A O?=H@E= A AHCO AJ=> EI JD=JE? HF H=JAI> JDB=JJO=?E@= @?=H> DO@H=JA AJ=> EI 9AJAIJA@JDA @A MEJDJM @EBBAHA JE @K?JE I B$EI?DA E= =H= FHA@K?JE? F AJA@ LAH! E = @=IJAFHA@K?JE? F AJA@ LAH E 6DAHAIK JI=CHAA@MEJD KHDOF JDAIAIJD=JJDAJM AJD @I B> @ B MHA@K?JE HAIK JE IE E =HIJA=@O IJ=JA AJ=> EJAL= KAI = JD KCDJDAJE A? KHIAI=HA@EBBAHA J 6DAIJA=@O IJ=JAANFAHE A J= L= KAIB HJEIIKAC O? CA = @ =?J=JA? JA J=J$ E KJAI BEI?DA E==CHAA@MA MEJDIE K =JA@HAIK JI D MALAHJDA @A IE K =JA@JE A? KHIAI@KHE CJDAJH= IEJE J $EI?DA E= =CCA@>ADE @B H> JDIK>IJH=JAI 1?? KIE JDEIIJK@O@A IJH=JAIJDA KJE EJO B? FKJAH @A IB HFHA@E?JE CANFAHE A J= KJ? AIE IJK@EAI B AJ=> E?HACK =JE K @AHFDOIE CE?= = @F=JD CE?=? @EJE I.KJKHA @A I D MALAH AA@J E? HF H=JA HA? F AN? JH A?D= EI IJ HA =??KH=JA OFHA@E?J@O = E??D= CAI )? M A@CA A JI 6DEIM H M=IIKFF HJA@>OJDA =JE = 1 IJEJKJAI B0A= JD / $$!' )5) 5*4110. # = @JDA) AHE?= 0A=HJ)II?E=JE '$$!##8 6DA =KJD HIMEIDJ JD= =LAA 5D=H = *HE@CAJJA+DHEIJ FDAH = @,H A I +D=LA B HJDAEH =IIEIJ=?A 4-.-4- +-5 )H=E)- /H=KAH5- ) IA A+/ 2= JA O/)= @*HEIJ M, AJ=> E?=@=FJ=JE J = CH=@K= HA@K?JE E O?=H@E= > @B M +EH?K =JE ''# ' "" # )H=E)- 2= JA O/) ) IA A+/ *HEIJ M = @*HEIJ M, )?JELA@ M HACK =JE B O?=H@E= A AHCOHAGKEHA A JI@KHE CFH CA@ @AH=JAEI?DA E=E IME A +EH?4AI '' $' "#& "$'! 2= JA O/) = A5) 4DA 95 ) IA A+/ )H=E) *HEIJ M = @*HEIJ M, 4ACA AH=JE B O?=H@E= FD IFD?HA=JE AE FECI@AIFEJA? JE KA@ @AH=JAEI?DA E= +EH? 4AI '' $% "& "'!
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