lecture 09 ch 7&9 allosteric hemoglobin opst-2

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Page 1: Lecture 09 Ch 7&9 Allosteric Hemoglobin Opst-2

7/24/2019 Lecture 09 Ch 7&9 Allosteric Hemoglobin Opst-2

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!"#$%&" ( )* + ,-. (

 /0012$"&3# 4&1$"3-2 ,-. 5"6170183-

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7/24/2019 Lecture 09 Ch 7&9 Allosteric Hemoglobin Opst-2

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7/24/2019 Lecture 09 Ch 7&9 Allosteric Hemoglobin Opst-2

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!"#$%&% ( )& #*+ ,+ -.%*+ /0)$+ 1223415678696:86;;

 /- 9:$&"6"0; 41$"-$ <-*383$1& 1=

>,-$*3-" ?:3.1&".%#$,2"

)@ABC/! BC@D)CD@9 ?EC59 9FGAH9I<F5<J<C?@

)?H4!9> /FK H9)5/F<BH

?E <F5<J<C<?F

C9<IL+MN OMIOPI#;,-1IQI

3218%$1:;R*"-;0SIQI6"$*;0ITI

$*3,U10"#,&81:;03# ,#3.S 32 ,- ":$&"6"0;

R1$"-$ 3-*383$1& 1= :,-$*3-"

1:3.1&".%#$,2"V B$",.; 2$,$" W3-"$3#2

6",2%&"6"-$2 ":*383$ 63:". $;R"3-*383$31- X3$* Y 3 ,-. Y 3Z [,0%"2 1= \VM

± NVNT × \N]\N 6 ,-. (± NVNT×

\N]\N 6^ &"2R"#$3["0;V

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7/24/2019 Lecture 09 Ch 7&9 Allosteric Hemoglobin Opst-2

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 /..3$31-,0 E,#$1&2

$*,$ /=="#$ 9-U;6" /#$3[3$;

\V 9-U;6" 9:R&"2231- !"["02

MV )1[,0"-$ H1.3=3#,$31-2

PV 9-[3&1-6"-$,0 E,#$1&2

QV <-*383$1&2

TV @"7%0,$1&; H10"#%0"2 O/0012$"&3# @"7%0,$1&2S

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7/24/2019 Lecture 09 Ch 7&9 Allosteric Hemoglobin Opst-2

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7/24/2019 Lecture 09 Ch 7&9 Allosteric Hemoglobin Opst-2

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)"&$,3- 9-U;6"2 ,&" B"-23$3[" @"7%0,$1&;

413-$2 3- H"$,8103# 4,$*X,;2

_ /0012$"&3# "-U;6"2 *,[" `1$*"& 2*,R"2a

_   !""#$ `1$*"&a $%&'&#$ `2*,R"a

_ J3-.3-7 1= 61.%0,$1& ,$ 1-" 23$" ,=="#$2 2%82$&,$" ,==3-3$;

,$ 1$*"& 23$"2

_ C*" b61.%0,$1&c 6,; 8"

_ $*" 2%82$&,$" 3$2"0= O#11R"&,$3[3$;S

?@_ , &"7%0,$1&; 610"#%0" 1$*"& $*,- $*" 2%82$&,$"

O,0012$"&3# &"7%0,$31-S

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 /0012$"&3# @"7%0,$31-I#1-$&10 1= , &",#$31- R,$*X,; 8; ,

6".3,$1& $*,$ #1-["&$2 ,- ,0012$"&3#

R&1$"3- =&16 b,#$3["c $1 ,- b3-,#$3["c 2$,$"

)"00%0,& `C*"&612$,$a

9:V E"".8,#W <-*383$31-

I/2 0"["0 1= <210"%#3-" &32"2^

R,$*X,; -"".2 $1 8" ̀ $%&-". .1X-a

I<210"%#3-" 83-.2 9-U;6" \ ,$

,0012$"&3# &"7%0,$1&; 23$" ,-.

#1-["&$2 $1 0"22 ,#$3[" 2$,$"

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7/24/2019 Lecture 09 Ch 7&9 Allosteric Hemoglobin Opst-2

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<- $*" R&"2"-#" 1=

,0012$"&3# 3-*383$1&^

"-U;6" *,2 01X ,==3-3$;

=1& 2%82$&,$"

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7/24/2019 Lecture 09 Ch 7&9 Allosteric Hemoglobin Opst-2

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<- $*" R&"2"-#" 1=

,0012$"&3# ,#$3[,$1&̂"-U;6" *,2 *37*,==3-3$; =1& 2%82$&,$"

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 /0012$"&3# 9-U;6"2 9:*383$ )11R"&,$3[3$;

_ C*" ̀ ,#$3["a ["&2%2 ̀ 3-,#$3["a 2$,$" 1= ,0012$"&3# "-U;6"2 32

-1$ 1-0; ."R"-."-$ %R1- ,0012$"&3# &"7%0,$1&2

_ @ O&"0,:".^ ,#$3["S [2 C O$"-2"^ 3-,#$3["S =1&62

_ B%82$&,$" 83-.3-7 ,021 ,=="#$2 `,#$3["a ["&2%2 `3-,#$3["a

2$,$"

_ ?=$"-^ 83-.3-7 1= 2%82$&,$" $1 1-" 2%8%-3$ #1-["&$2 1$*"&2%8%-3$O2S $1 ,#$3[" 2$,$"

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d*; ,&" ,0012$"&3# "-U;6"2

O,2 1RR12". $1 HH "-U;6"2S

2"-23$3[" $1 ,0012$"&3# &"7%0,$31-e

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 /0012$"&3# 9-U;6"2 9:*383$ )11R"&,$3[3$;

_ /0012$"&3# &"7%0,$31-f#11R"&,$3[3$; 32 R122380" X3$*

)*!%&'+!',  R&1$"3-2 1-0;

_ 9:,6R0"g 4123$3[" )11R"&,$3[3$;

_ J3-.3-7 1= 2%82$&,$" $1 1-" 2%8%-3$ 3-#&",2"2,#$3[3$;f,==3-3$; 1= &"6,3-3-7 2%8%-3$2 OC! @

#1-["&231-S

_ M H1."02

_ )1-#"&$". H1."0

_ B"h%"-$3,0 H1."0

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)1-#"&$". H1."0

I/00 2%8%-3$2 "3$*"& 3- @ 1& C =1&6

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B"h%"-$3,0 H1."0

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4123$3[" )11R"&,$3[3$; R&1.%#"2 ,237613.,0 #%&["

d*;e

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 /0012$"&3# 9-U;6"2 B"-2" B37-,02

_ /0012$"&3# @"7%0,$1&2

_ /0$*1%7* ,0012$"&3# "-U;6"2 %-."&71 <=><&?#&) *)@)*

&"7%0,$31- OR123$3[" #11R"&,$3[3$;S^ #**%<&)?.A ?)B=*#&%?<,&" #&3$3#,00; 36R1&$,-$ 3- 6,3-$,3-3-7 ,RR&1R&3,$" 0"["02

1= "-U;6,$3# ,#$3[3$;

_ H,-3="2$2 ,2 bE"".8,#W <-*383$31-c O1& R123$3["

2$36%0,$31-S

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!

IB%82$&,$" 83-.2

I`C&,R2a $*" @ O,#$3["S =1&6

I*,2 7&",$"& ,==3-3$; =1&

2%82"h%"-$ 2%82$&,$"

610"#%0"2 O,..3$31-,0 ,[,30,80"83-.3-7 23$"S

"!

I/0012$"&3# &"7%0,$1& 83-.2

I`C&,R2a $*" @ O,#$3["S =1&6

I*,2 7&",$"& ,==3-3$; =1&

2%82$&,$" 610"#%0"2

"#$ %#$

I/0012$"&3# &"7%0,$1& 83-.2

I`C&,R2a $*" C O3-,#$3["S

=1&6

I*,2 0"22 ,==3-3$; =1&

2%82$&,$" 610"#%0"2

!&'()*+),%-./&0,/

23(-)-4, 5336,*+)-4-)7

23(-)-4, #883(),*-0

$,9&8+)-3.

:,9+)-4, #883(),*-0

$,9&8+)-3.

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<2 )C4 , HH 3-*383$1& 1& ,- ,0012$"&3# &"7%0,$1&e

4123$3[" 1& -"7,$3[" "=="#$2e

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<2 /C4 , R123$3[" 1& -"7,$3[" ,0012$"&3# &"7%0,$1&e

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H3#*,"032IH"-$"- <-*383$31-

[2V /0012$"&3# @"7%0,$31-

_   ;; ,.<7=,( /3 .3) &./,*93 +883(),*-0 *,9&8+)-3.

 i   5+. ', -.>-'-),/ '7 )3?-.( 3* /*&9( @;; -.>-'-)-3.A

 i   #0)-4-)7 -( +BB,0),/ '7 C!D +./ C2D

 i   E&) :FG -. )>, (+=, H+7 )>+) +883(),*-0 *,9&8+)3*( +./ C!D +BB,0)+883(),*-0 6*3),-.(

_   I. 683) 3B C!D 4( J3 %%%%%>76,*'38-0 0&*4,

_   #883(),*-0 ,.<7=,( >+4, /-()-.0) 6>7(-0+8 +./ K-.,)-0 6*36,*)-,(

 i  L&+),*.+*7 ()*&0)&*,

 i   #883(),*-0 ,.<7=,( M(,.(,N (-9.+8( +./ *,(63./

_   :FG )>, (+=, +( + ;; ,.<7=, ',-.9 -.>-'-),/ '7 + )3?-. 3* /*&9 i   !&'&.-)( /-(68+7 0336,*+)-4-)7 @*,(63./ )3 (-9.+8( (&0> +( C!D +./

6*,(,.0, 3B +883(),*-0 *,9&8+)3*(A +./ ,?-() -. )H3 ()+),( @+0)-4, 3*-.+0)-4, #O# P*,8+?,/Q 3* P),.(,QA

_   I. 683) 3B C!D 4( J3%%%%%%!-9=3-/+8 0&*4,

G>, +'-8-)7 3B +883(),*-0 6*3),-.( )3 (,.(, +./ *,(63./ )3 (-9.+8( -( B&./+=,.)+8

)3 34,*+88 033*/-.+)-3. 3B 0,88&8+* 6*30,((,(

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_ )16R,&" ,-. #1-$&,2$ 1:;7"- 83-.3-7 3- 6;170183- [2 *"6170183-

_ K32#%22 $*" 610"#%0,& 8,232 =1& #11R"&,$3[3$; 3- 1:;7"- 83-.3-7 $1

*"6170183-

_ 9:R01&" ,0012$"&3# &"7%0,$1&2 1= *"6170183-

_ J"#16" =,6303,& X3$* 23#W0" #"00 ,-"63, ,-. )? "=="#$2 1- *"6170183-

!",&-3-7 ?8j"#$3["2

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?:;7"- C&,-2R1&$

,-. /0012$"&3# @"7%0,$31-

_ H;170183-

_ F"". ,[,30,80" 1:;7"- =1& 6"$,810326

_ 4&1$"3- 23."I#*,3-2 0,#W ,==3-3$; =1& ?M

_ ?&7,-16"$,003# #16R1%-.2 2%#* ,2

*"6" ,&" 61&" 2%3$,80" i B10%$31-g

_ ),R$%&" 1:;7"- 610"#%0"2 X3$* *"6"

2"h%"2$"&". 3-23." $*" 6;170183-

R&1$"3-

_ /001X2 1:;7"- $1 .3==%2" $*&1%7*

6%2#0" #"002 ,2 -"".".

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H;170183- ,-. ?:;7"- J3-.3-7

5"6" 32 ,

R&12$*"$3#

7&1%R

_ H;170183- #16R12". 1= k l *"03#"2

_ / i 5

_ B"h%"2$"&2 1:;7"- %23-7 *"6"

R&12$*"$3# 7&1%R

_ 5;.&1R*183# R1#W"$ 8"$X""-

*"03#"2 9 ,-. E

_ 4&1$"#$2 3&1- 1= *"6" =&16

1:3.,$31-

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_ <- E"Mm 2$,$"

_ ),- =1&6 M ,..3$31-,0

81-.2^ 1-" 1- ",#* 23." 1=

R0,-,& R1&R*;&3- &3-7

_ ?-" R123$31- #11&.3-,$".

X3$* 532 23." #*,3-

_ ?$*"& ,[,30,80" =1& 1:;7"-

83-.3-7

4&1R31-,$" 7&1%R2 ":R12". $1

210["-$

CX1 [3-;0 7&1%R2 8%&3". 3-

*;.&1R*183# R1#W"$ 1= 6;170183-

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d*; *"6170183- O8%$ -1$ 6;170183-S

32 , 711. 1:;7"- %'!+$-#'%&' 

_ H;170183- 32 , 61-16"& O\ *"6" 7&1%RS

_ 5"6170183- 32 , $"$&,6"& _ Q *"6" 7&1%R2

_ /0012$"&3# R&1$"3- O*,2 h%,$"&-,&; 2$&%#$%&"S

)11R"&,$3[3$;

 /0012$"&3# @"7%0,$31-

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Q *"6"I81%-. 2%8%-3$2 3-

*"6170183- n Q ?M

610"#%0"2 #,- 8" 81%-.

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)1%0. H;170183- d1&W

,2 , o11. ?M C&,-2R1&$"&e

_ R?M 3- 0%-72 32 ,81%$ \P W4,g 3$ 83-.2 1:;7"- X"00

_ R?M 3- $322%"2 32 ,81%$ Q W4,g 3$ X300 -1$ &"0",2" 3$p

   H  ;  1  7   0  1   8   3  -

   ?  :  ;  7  "  -  I   J  1  %

  -   .   E  &  ,  #   $   3  1  -

;&(08,

( +B),*,?,*0-(,

R&.9( 3.

3?79,.

)*,+)=,.)

R&.9(

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5"6170183-

_ E1%-. 3- @J)2IIIPNN 630031- 610"#%0"2 R"& @J)

_ 4&36,&; 1:;7"- $&,-2R1&$ *"6" R&1$"3-

_ C"$&,6"& 1= $X1 2%8%-3$2 O$X1 3."-$3#,0 .36"&2g ,\8\^ ,M8MS

_ 9,#* 2%8%-3$ 32 23630,& $1 6;170183-_ <&1- 2$,8303U". X3$*3- *"6" R&12$*"$3# 7&1%R

_ B"h%"2$"&". 3- *;.&1R*183# R1#W"$

_ 532 Ek 037,-.2 E" 31-

_ 532 9+ =1&62 *;.&17"- 81-. X3$* ?M

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B$&1-7 *;.&1R*183#3-$"&,#$31-2 2$,8303U" lq

2%8%-3$2

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K36"&2 *"0. 3-,221#3,$31- 8; X",W 31-3#

,-. *;.&17"- 81-.2

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5"6170183-

_ 537* ,==3-3$; =1& 1:;7"- ,$ *37* R,&$3,0R&"22%&" 1= ?M OR?MS ,-. 01X ,==3-3$;

=1& 1:;7"- ,$ 01X R?M

 i / R01$ 1= =&,#$31-,0 2,$%&,$31- O1:;7"-

83-.3-7S ,-. 1:;7"- #1-#"-$&,$31-

OR?MS 32 237613.,0

 i 4,&$3#%0,&0; &"2R1-23[" $1 #*,-7"2 3-

R?M ,$ 61."&,$" #1-#"-$&,$31-

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5"6170183-

H%2#0"2

,=$"&":"&#32"

!%-72 1-

1:;7"-$&",$6"-$

!%-72

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5"6170183-

H%2#0"2

,=$"&":"&#32"

!%-72 1-

1:;7"-$&",$6"-$

!%-72

S+8B 3B3?79,.

*,8,+(,/

#88 3B

3?79,.

*,8,+(,/

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I 0+.N) 8,) 93T

#) )>, 3?79,. 03.0,.)*+)-3. B3&./ -. =&(08,

)-((&,( /&*-.9 )>, -.-)-+8 6>+(,( 3B ,?,*0-(,

UV ;73983'-. H-88 ', >-9>87 (+)&*+),/ H-)>3?79,.

WV S,=3983'-. H-88 ', >-9>87 (+)&*+),/ H-)>

3?79,.

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I 0+.N) 8,) 93T

#) )>, 3?79,. 03.0,.)*+)-3. B3&./ -. =&(08,

)-((&,( /&*-.9 )>, -.-)-+8 6>+(,( 3B ,?,*0-(,

UV S,=3983'-. H-88 *,8,+(, 3?79,. )3 .3&*-(>0,88(

WV ;73983'-. H-88 *,8,+(, 3?79,. )3 .3&*-(>

0,88(

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_ )16R,&" ,-. #1-$&,2$ 1:;7"- 83-.3-7 3- 6;170183- [2 *"6170183-

_ K32#%22 $*" 610"#%0,& 8,232 =1& #11R"&,$3[3$; 3- 1:;7"- 83-.3-7 $1

*"6170183-

_ 9:R01&" ,0012$"&3# &"7%0,$1&2 1= *"6170183-

_ J"#16" =,6303,& X3$* 23#W0" #"00 ,-"63, ,-. )? "=="#$2 1- *"6170183-

!",&-3-7 ?8j"#$3["2

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51X ),- 58 /==3-3$;

=1& ?:;7"- )*,-7" !3W" C*32e

5"6170183- *,2 6%0$3R0" 83-.3-7 23$"2

 /-. $*" 83-.3-7 23$"2 3-$"&,#$ X3$* ",#* 1$*"& 

 i B37-,0 =1& #11R"&,$3[3$;f,0012$"&3# &"7%0,$31- #166%-3#,$".

$*&1%7* 31-3# 81-.2 O2,0$ 8&3.7"2S ,$ $*" 3-$"&=,#" 8"$X""-

2%8%-3$2

C*" =1%&$* ?M 610"#%0" $,W"- %R 8; *"6170183- 83-.2

X3$* r\NN $36"2 7&",$"& ,==3-3$; $*,- =3&2$

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<- ."1:;*"6170183-^ E" *,2 1-0; T

037,-.2

!3"2 2037*$0; 1%$23." *"6" &3-7

<- ,221#3,$31- X3$* 532 Ek

d*"- 1:;7"-,$".^ 3&1- &32"2 3-$1 &3-7

4%002 E *"03: ,2 X"00

@1$,$"2 "-$3&" lq .36"& 

! )?FE?@H/C<?F/! )5/Fo9

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 /2 1:;7"-,$31- ,0$"&2 2%8%-3$

R123$31-^ $*" *"6170183-

610"#%0" #*,-7"2 3-

h%,$"&-,&; 2$&%#$%&"

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G+K, =, H-)> 73&XX

#B),* 3?79,. '-./( )>, -*3. -. )>, >,=, *-.9 3B

>,=3983'-.Y

UV G>, -*3. +)3= ',03=,( 8+*9,*

WV S-( Z[ +.0>3*( )>, -*3. +)3= 3&)(-/, )>,

63*6>7*-. *-.9

\V G>, >,=, 9*3&6 /-((30-+),(]V I3.-0 '3./( -. )>, +86>+Y',)+ /-=,* -.),*B+0,

+*, /-(*&6),/

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@ ,-. C B$,$"2 1= 5"6170183-

C n C"-2" 2$,$" O."1:;*"6170183-S

 i ?M 83-.3-7 $&377"&2 , C @ #1-=1&6,$31-,0 #*,-7"

@ n @"0,:". 2$,$"^ *37*"& ,==3-3$; =1& ?M $*,- $*" C 2$,$"

)1-=1&6,$31-,0 #*,-7" =&16 $*" C 2$,$" $1 $*" @ 2$,$"

3-[10["2 .32&%R$3-7 31- R,3&2 8"$X""- $*" !" .36"&

3-$"&=,#" i !1X ?M 2$,$"^ 31-3# 3-$"&,#$31- ,$ 3-$"&=,#"

 i DR1- ?M 83-.3-7^ 3&1- 2*3=$2 R123$31-^ 61["2 ,221#3,$". 532 ,-.

.32&%R$2 $*" 3-$"&=,#"

_ C =1&6g 2,0$ 8&3.7" 3-$,#$

_ @ =1&6g 2,0$ 8&3.7" .32&%R$".

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@"#,00g K36"&2 *"0.

$17"$*"& 8; X",W 31-3#

,-. *;.&17"- 81-.2

<- b$,%$c C 2$,$"^ k

61&" 2,0$ 8&3.7"2

8"$X""- 2%8%-3$2 $*,-

b&"0,:".c @ =1&6

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s%,$"&-,&; 5"6170183- ":*383$2

#11R"&,$3[3$; X3$* 3-#&",23-7 1:;7"-

,[,30,8303$;

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C*" 1:;7"- .3221#3,$31- #%&[" =1&

6;170183- *,2 , *;R"&8103# 2*,R" $*,$&"=0"#$2 $*" =,#$ $*,$g

\V H;170183- &"["&2380; 83-.2 , 23-70"

610"#%0" 1= 1:;7"-

MV H;170183-c2 Q 2%8%-3$2 #11R"&,$" 3-83-.3-7 1:;7"-

PV C*" ."1:; =1&6 1= 6;170183- 32 3- $*" @I

2$,$"

QV H;170183- *,2 , 01X"& 1:;7"- ,==3-3$;$*,- *"6170183-

TV H;170183- *,2 *"6" ,-. *"6170183-.1"2 -1$

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_ )16R,&" ,-. #1-$&,2$ 1:;7"- 83-.3-7 3- 6;170183- [2 *"6170183-

_ K32#%22 $*" 610"#%0,& 8,232 =1& #11R"&,$3[3$; 3- 1:;7"- 83-.3-7 $1

*"6170183-

_ 9:R01&" ,0012$"&3# &"7%0,$1&2 1= *"6170183-

_ J"#16" =,6303,& X3$* 23#W0" #"00 ,-"63, ,-. )? "=="#$2 1- *"6170183-

!",&-3-7 ?8j"#$3["2

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5"6170183- ,-. ?:;7"- C&,-2R1&$

<- 1&."& $1 83-. 1:;7"- 3- $*" 0%-72 ,-. &"0",2" 1:;7"- 3-$322%"2tV

5"6170183-c2 ,==3-3$; =1& 1:;7"- 32 &"7%0,$". 8; ,$ 0",2$ Q

=,#$1&2 i ?M 0"["02 O)11R"&,$3[3$;S

 i ,-. /0012$"&3# @"7%0,$1&2

_ )?M 0"["02

_ R5_ M^PIJ4o

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5"6170183- ,-. )?M 9:R1&$

)?M 32 R&1.%#". 8; 6"$,810326 3- $322%"2 ,-. 6%2$ 8" ":R1&$".

 i K3==%2"2 $1 @J)2^ =1&62 #,&81-3# ,#3.!83#,&81-,$"

 i /021^ ":R1&$". 3- $*" =1&6 1= , #,&8,6,$" 1- FI$"&63-3 1=

*"6170183- 2%8%-3$2

 i )1-="&2 -"7,$3[" #*,&7" 1- $"&63-,0 ,63-1 7&1%R2^ X*3#* 03" 3- lq

3-$"&=,#"

_ F"7,$3[" #*,&7"II=,[1&2 2,0$ 8&3.7" =1&6,$31-

)?M 81%-. $1 *"6170183- 2$,8303U"2 C =1&6 i @"0",2" ?M

58IF5M m )?M   58IF5I)??I m 5m

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R5 9=="#$ 1- ?M J3-.3-7 $1 5"6170183-

J011. 3- 0%-72 R5 u 8011. 3- #,R300,&3"2 1= 6"$,8103#,00; ,#$3[" $322%"2

58 ,==3-3$; =1& 1:;7"- ."R"-."-$ %R1- R5

 i ?:;7"- &"0",2". ,$ 01X"& R5vC 2$,$" =,[1&".

_ <1-3# 81-.2 .%" $1 R&1$1-,$". 1= 532 &"23.%"2 ,$ .36"& 3-$"&=,#"

 i ?:;7"- 2"h%"2$"&". ,$ *37*"& R5 i@ 2$,$" =,[1&".

s%"2$31-2g

<- 0%-72g 537*"& R5^ 537* 1:;7"-vX*3#* =1&6 R&".163-,$"2e

<- 6"$,8103#,00; ,#$3[" $322%"2g !1X"& R5^ !1X 1:;7"-vd*3#* =1&6

R&".163-,$"2e

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R5 9=="#$ 1- ?M J3-.3-7 $1 5"6170183-

<- $322%"2^ 1:;*"6170183- 3- @I2$,$"

O."R&1$1-,$". 23." #*,3-2S ,##"R$2 R&1$1-2

&"0",2". .%&3-7 6"$,810326 O3V"V 0,#$3# ,#3. 1&

#,&81-3# ,#3.S

@! C #1-["&231- =,[1&2 &"0",2" 1= 1:;7"-

<- 0%-72^ ."1:;*"6170183- 3- C 2$,$" &"0",2"2

R&1$1-2 3- *37*"& R5 "-[3&1-6"-$ O.%" $1

":*,0,$31- 1= )?MS

C! @ #1-["&231- =,[1&2 83-.3-7 1:;7"-

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I)?M 32 $&,-2R1&$". $1 0%-72 1- 58 ,-. ,2 83#,&81-,$"

I5m 31-2^ X*3#* #1-$&38%$" $1 -%0? )CC)A&D ,&" 7"-"&,$". .%&3-7

83#,&81-,$" =1&6,$31-

v83-. 532 &"23.%"2 $1 =,[1& C 2$,$"I1:;7"- &"0",2"

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<- $*" 0%-72^ &".%#". )?M #1-#"-$&,$31- .%" $1 ":*,0,$31-

I=,[1&2 83#,&81-,$" m 5m ! )?M ,-. 5M?

I3-#&",23-7 R5 0",.2 $1 ."R&1$1-,$31- 1= 532 &"23.%"2v@ 2$,$" =,[1&".

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J<o 4<)CD@9g

_ 537* w)?Mx ,-. w5mx 2$,8303U" C =1&6 1= 58 3- $322%"2

_ !1X w)?Mx ,-. w5mx 0",. $1 C!@ #1-["&231- 3- 0%-72

.#""&/% #0,1&+ 23&'& 4#$% !5*+6!+% 

7&"89&' #0,1&+ 23&'& 4#$% +&&6&6 

@"7%0,$31- 1= ? J3-.3-7 8;

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@"7%0,$31- 1= ?M J3-.3-7 8;

M^PIJ32R*12R*170;#"&,$" OM^PIJ4oS

M^PIJ4o ."#&",2"2 *"6170183-c2 1:;7"- ,==3-3$;

 i J3-.2 ."1:;*"6170183- ,-. 2$,8303U"2 C 2$,$"

 i !"["02 &"7%0,$". $1 ,..&"22 *;R1:3# 23$%,$31-2

E"$,0 *"6170183- 0,#W2 M^PIJ4o 83-.3-7 23$"I6,$"&-,0 ! ="$,0 1:;7"- $&,-2="& 

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d*3#* =,#$1&2 2"&[" $1 &"0",2" 1:;7"- 3-

$322%"2g

\V !1X )?M

MV 90"[,$". w5mx

PV !1X M^P J4o

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_ )16R,&" ,-. #1-$&,2$ 1:;7"- 83-.3-7 3- 6;170183- [2 *"6170183-

_ K32#%22 $*" 610"#%0,& 8,232 =1& #11R"&,$3[3$; 3- 1:;7"- 83-.3-7 $1

*"6170183-

_ 9:R01&" ,0012$"&3# &"7%0,$1&2 1= *"6170183-

_ J"#16" =,6303,& X3$* 23#W0" #"00 ,-"63, ,-. )? "=="#$2 1- *"6170183-

!",&-3-7 ?8j"#$3["2

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o"-"$3# 6%$,$31- 3- *"6170183- 7"-"

I1-" -1-#1-2"&[,$3[" ,63-1 ,#3. 2%82$3$%$31-I,77&"7,$"2 %-."& *;R1:3# #1-.3$31-2

B3#W0" #"00 ,-"63,

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),&81- H1-1:3." 41321-3-7

)? 83-.2 $37*$0; $1 *"6170183- 3&1-

J3-.3-7 1= )? 1- 1-" *"6" 23$" -"7,$3["0; ,=="#$2 1:;7"-

83-.3-7 1- &"6,3-3-7 23$"2