• No results found

Marc A. Seelen





 



  Blocking complement factor B activation reduces renal injury and inflammation in a rat brain death model

Frontiers of Immunology; 2019

Neeltina M. Jager Judith E. van Zanden Marta Subias

Henri G. D. Leuvenink Mohamed R. Daha

Santiago Rodriquez de Cordoba Felix Poppelaars

Marc A. Seelen

559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager Processed on: 10-5-2021 Processed on: 10-5-2021 Processed on: 10-5-2021

Processed on: 10-5-2021 PDF page: 180PDF page: 180PDF page: 180PDF page: 180

 QXP

'(&(

"(&#)(#"

'!.+06(9?0%,( /!?7:7! %0696/74-/99(0/6!6!96(!<! %60.6(/X ! 06&/ 0/067R

/ 6(/ !9'O 9'! (66!<!67(-! -077 0% 6(/ %:/9(0/7 6!7:-97 (/ '!.0 ?/.( (/79(-(9?O

'06.0/-'/&!7/ (..:/0-0&(-9(<9(0/R!!/9-?O6(/ !9''7!!/7'0=/90

:7!9(<9(0/0%9'!0.4-!.!/97?79!.O='('(7 <!67!-?770(9! =(9'6!/---0&6%9

0:90.!(/6!(4(!/97R0 :-9(0/0%9'!0.4-!.!/97?79!.(/9'!6(/X !  0/06.(&'9

!  460.(7(/& 7969!&? 90 (.460<! 06&/ 5:-(9? !%06! 96/74-/99(0/R '(7 79: ?

(/<!79(&9! 9'!!%%!90%/(/'((906?/9(0 ?&(/790.4-!.!/9%9060/6(/ !9'X (/ :! 6!/-(/%-..9(0// (/+:6?R



(#

6(/ !9'=7(/ :! (/.-!(7'!6697?(/%-9(/&--00/9'!9!6(/9'!!4( :6-

74!R/9(X%906Z/9(X[067-(/!=7 .(/(79!6! (/96<!/0:7-?fd.(/:9!7!%06!9'!

(/ :9(0/0%6(/ !9'Z/xlW&60:4[R'.X04!69! 6977!6<! 70/960-7Z/xh[R%9!6h

'0:670%6(/ !9'O6!/-%:/9(0/O6!/-(/+:6?/ (/%-..9(0/=!6!77!77! R



') ('

6!96!9.!/9 =(9'/9(X 6!7:-9!  (/ 7(&/(%(/9-? -!77 7?79!.( /  -0- 0.4-!.!/9

9(<9(0/ 9'/ (/ 7-(/!X96!9!  697 %9!6 6(/ !9'R 06!0<!6O /9(X 96!9.!/9

46!7!6<! 6!/-%:/9(0/O6!%-!9! ?7(&/(%(/9-?6! :! 7!6:.6!9(/(/!-!<!-70.46!  90 7-(/!X96!9!  697 %9!6 h '0:67 0% 6(/ !9'R :69'!6.06!O /9(X 7(&/(%(/9-?

99!/:9!  '(790-0&(- (/+:6?O 7 7!!/ ? 6! :!  9::-6 (/+:6? 706!7O -0=!6 6!/- &!/!

!>46!77(0/-!<!-7Zzkiu[/ 6!/- !407(9(0/0%,( /!?(/+:6?.6,!6XeR/ (9(0/O/9(X

96!9.!/97(&/(%(/9-?46!<!/9! 6!/-.604'&!(/%-:>/ 6! :! 7?79!.( Xj-!<!-7

0.46! 907-(/!X96!9! 697%9!66(/ !9'R 79-?O6!/-&!/!!>46!77(0/0% XjOX e/ Xe=!6!7(&/(%(/9-?6! :! (/69796!9! =(9'/9(XR



#" )'#"

'(779: ?7'0=79'9 0/0646!96!9.!/9=(9'/9(X46!7!6<! 6!/-%:/9(0/O6! :!  6!/- .&!/ (/%-..9(0/46(069096/74-/99(0/R'!6!%06!O(/'((9(0/0%%906(/

06&/ 0/067.(&'9!460.(7(/&7969!&?906! :!6(/ !9'X(/ :! 6!/-(/+:6?/  (/%-..9(0/R

 

559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager Processed on: 10-5-2021 Processed on: 10-5-2021 Processed on: 10-5-2021

Processed on: 10-5-2021 PDF page: 181PDF page: 181PDF page: 181PDF page: 181

 QXQ

"(&#)(#"

-9'0:&'9'!%(!- 0%6!/-96/74-/99(0/'7. !':&!460&6!770<!69'!-79id?!67O0/!

0%9'!.(/'--!/&!76!.(/79'! (746(9?!9=!!/ !./ / 7:44-?0%6!/---0&6%97R 

'!6!%06!O(/6!7(/&!%%06976!. !90!>4/ O:9-7090049(.(@!9'!:66!/9 0/06400-R

( /!?76!6!96(!<! %60.-(<(/& 0/067O !!7! %9!6(6:-906? !9'Z[ 0/067/  !!7! %9!66(/ !9'Z[ 0/067R!74(9!9'!(/6!7(/&/:.!60%-(<(/& 0/067O9'!

.+06(9?0%,( /!?76!79(--6!96(!<! %60.6(/X !  0/067R 

0=!<!6O 6(/ !9' (/ :!7 4'?7(0-0&(- (79:6/!7 '69!6(7!  ?

'!.0 ?/.( '/&!7O .!90-( (79:6/!7O /  (..:/0-0&(- !6/&!.!/97R

'!6!%06!O,( /!?76!96(!<! %60.6(/X !  0/067&(<!(/%!6(066!7:-97O6!%-!9! ?'(&'!6

69!0% !-?! &6%9%:/9(0/9'/9'!(6-(<(/&0:/9!64697R/(.4069/9 !/0.(/906(/

6(/ !9'X(/ :!  6!/- (/%-..9(0/ (7 9(<9(0/ 0% 9'! 0.4-!.!/9 7?79!.R '!

0.4-!.!/97?79!./!9(<9! ?9'6!! (%%!6!/949'=?7Q9'!-77(-49'=?Z[O

9'!-!9(/49'=?Z [/ 9'!-9!6/9(<!49'=?Z[R9(<9(0/0%!'0%9'!7!9'6!!

49'=?7 6!7:-97 (/ 9'! -!<&! 0% 0.4-!.!/9 0.40/!/9 g (/90 g /  gR

:7!5:!/9-?O9(<9(0/0%g-! 7909'!%06.9(0/0%9'!i0/<!697!7O='('-!<!i

(/90i/ iRi(79'!(/(9(-4609!(/%069'!%06.9(0/0%iXmO-70,/0=/79'!

.!.6/! 99, 0.4-!> Z[R '!  (/ :!7 9'! %06.9(0/ 0% 406!7 (/ 9'! !--

.!.6/!O='('6!7:-97(/!---?7(7R!7( !7OiXm(/ :!79(77:!(/+:6?<((/96!--:-6460X (/%-..906?7(&/-(/&49'=?7R/ (9(0/O9'!/4'?-90>(/7g/ i6!460 :! O

='('460<0,!(/%-:>/ 9(<9(0/0%(/%-..906?!--7R

6-?79: (!7-6! ?'<! !.0/7969! 9'!46!7!/!0%0.4-!.!/9g(/,( /!?7

%60.6(/X ! 697Rg !407(9(0/=77!!/0/!/ 09'!-(-!--7/ (/9'!&-0.!6:-(0%

X !6(<!  ,( /!?7O ='(-! /0 g !407(9(0/ =7 07!6<!  (/ 6!/- (047(!7 %60. -(<(/&

0/067R/-(/!=(9'9'!7!6!7:-97Og  !407(9(0/=7 !9!9! (/6!/-(047(!7%60.':./

6(/X !  0/067!%06!6!4!6%:7(0/O='('7:&&!799'9g =7 !407(9! 7 (6!96!7:-9

0%6(/ !9'(97!-%R0.4-!.!/9g9(<9(0/6!7:-97(/9'!460 :9(0/0%9'! 0=/796!.

9(<9(0/460 :97i/ iXmO='('6!09'7?79!.(--?/ -0--?:46!&:-9! (/9'!

6(/X !  0/06R  '!7!79: (!7 !.0/7969!9'99'!0.4-!.!/97?79!.(79(<9! (/

6(/X !  0/067R'!6!%06!O(/'((9(0/0%9'!0.4-!.!/97?79!..(&'9!/9969(<!

7969!&?9099!/:9!6(/ !9'X(/ :! 6!/-(/+:6?/ (/%-..9(0/R

 409!/9(- 96&!9 %06 (/9!6<!/9(0/ (/ 9'! 6(/X !  0/06 .(&'9 ! 0.4-!.!/9

%906R906(70/!0%9'!,!?0.40/!/976!5:(6! %069(<9(0/0%9'!0.4-!.!/9

R O/9(<!%6&.!/90%%906O(77(&/(%(/9-?!-!<9! (/4-7.%60.6(/X !  0/067 0.46!  90 -(<(/& 0/067R  '!7! !-!<9!  4-7. -!<!-7 0%  6! 407(9(<!-?

066!-9!  =(9' 7?79!.( iXm -!<!-7 (/ 6(/X !  0/067R (&' 7?79!.( iXm -!<!-7 (/

6(/X !  0/0676!770(9! =(9''(&'!6(/( !/!0%:9!6!+!9(0/(/9'!6!(4(!/9R  / (9(0/O-0-6!/-!>46!77(0/0%%906=77(&/(%(/9-?(/6!7! (/,( /!?7%60.6(/X !  0/0670.46! 90,( /!?7%60.-(<(/& 0/06797!-(/!R '!7!79: (!7 !.0/7969!

9'9%906(709'7?79!.(--?/ -0--?:46!&:-9! (/,( /!?7%60.6(/X !  0/067R

8

559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager Processed on: 10-5-2021 Processed on: 10-5-2021 Processed on: 10-5-2021

Processed on: 10-5-2021 PDF page: 182PDF page: 182PDF page: 182PDF page: 182

 QXR

'!6!%06!O(/'((9(0/0%%9060:- !6(9(-904609!9&(/796(/ !9'X(/ :! 6!/-

(/+:6?R 0 0:6 ,/0=-! &!O /0 79: (!7 '<! (/<!79(&9!  ='!9'!6 (/'((9(0/ 0% %906  (7

9'!64!:9(--? !%%!9(<! (/ 6(/X !  0/067R :6 79: ? (.!  90 (/<!79(&9! ='!9'!6

(/'((9(0/0%%906/99!/:9!6(/ !9'X(/ :! 6!/-(/+:6?/ (/%-..9(0/R0 0

70O=!46!96!9! 697=(9'.0/0-0/-/9(0 ?&(/79%906Z/9(X[/ 7:7!5:!/9-?

7:+!9! 69790h'0:670%6(/ !9'R!%0:/ 9'946!96!9.!/90%9'! 0/06=(9'/9(X

7(&/(%(/9-?(.460<! 6!/-%:/9(0/O6! :! 6!/- .&!/ (/%-..9(0/(/6(/X

! 69746(069096/74-/99(0/R 

559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager Processed on: 10-5-2021 Processed on: 10-5-2021 Processed on: 10-5-2021

Processed on: 10-5-2021 PDF page: 183PDF page: 183PDF page: 183PDF page: 183

 QXS

(& " (#'

,$&!"( #)( "

/9'(779: ?Off697=!6!6/ 0.-? (<( ! (/909'!%0--0=(/&&60:47Z(&:6!e[Q

X 6(/ !9'=(9'7-(/!Z0/960-&60:4[Z/xl[

X 6(/ !9'=(9'/9(X%906Z/9(X[Z/xl[

F '.X04!69(0/=(9'7-(/!Z/xh[

 ,)?7$+ &-)- .&+/') $%+#*+9,'7 

,$+3/$+2#?2#2/50-)$+2#-$3/)0-2#/,3"#!/,+2,)2/),/#,)$+

2#0(3))+$+!)20),5)7,4/SP*$+320BHI)$+,/HI+2$F!2,/H+2$FI50*$+$02/

4$2#!*,/)4$+RP*$+320!,/2#$+32$,+,!/$+2#B!2/T#,3/0,!/$+2#?/20

5/0/$!$+),,?3/$++($+705/,))2B+HI0#*F,-/2/20?#,)50

/$))$+2#0(3))5$2#,32$+0/2$,+,!2#)),,+2#2/+/205/4+2$)2!,/SP*$+320

3+/+02#0$!,/0/$!$B/4$2$,+0A\?2/*$+2$,+@+2$F?+2$F!2,/B



('

 :-9.-!(7'!6ghhW 7 697Z/<(&0O:-(/OO[!9=!!/fidXgdd&6.7=!6!

:7! R976!!(<! %00 / =9!6 R--!>4!6(.!/97=!6!4!6%06.! 99'!-0-

/(.-%(-(9?0%9'!/(<!67(9?! (-!/96!60/(/&!/06 (/&909'!>4!6(.!/970/

/(.- 9 Zemmj[ (77:!  ? 9'! (/(796? 0% :-( !-9'O !-%6! /  40697 0% 9'!

!9'!6-/ 7R

8

559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager Processed on: 10-5-2021 Processed on: 10-5-2021 Processed on: 10-5-2021

Processed on: 10-5-2021 PDF page: 184PDF page: 184PDF page: 184PDF page: 184

 QXT

&"($&#)&

09!79='!9'!6(/'((9(0/0%9'!0.4-!.!/94609!97&(/796(/ !9'X(/ :! 6!/-

(/+:6?O =! 96!9!  6(/X !  697 =(9'  .0:7! /9(X':./ .0/0-0/- /9(0 ? &(/79

%906ZflRhRf[460 :! (/9'!-06906?0%460%R 6R/9(&00 6(5:!@ !06 09

(/'((906?/9(0 ?O='('96&!97/!<0-:9(0/6?X0/7!6<! !4(904!(/9'!%6&.!/90%

%906R/9(X!%%((!/9-?(/'((979'!%06.9(0/0%9'!g4600/<!697!(/':./7O697

/ 09'!674!(!7?-0,(/&9'!(/9!69(0/!9=!!/9'! 0.(/0%%906/ gR 

=!/9?.(/:9!7!%06!9'!0/%(6.9(0/0%6(/ !9'Ol.&0%4:6(%(! /9(X(/909-

<0-:.!0%kidJ-O=7 .(/(79!6! <(9'!%!.06-<!(/R-(/!O:7! (/9'!0/960-&60:4/  7'.X04!69! &60:4O=7-70 .(/(79!6! <(9'!%!.06-<!(/99'!7.!9(.!/ (/9'!

7.!<0-:.!7/9(XR6(/ !9'=7(/ :! 7 !76(! 46!<(0:7-?R 6(!%-?O697=!6!

/!79'!9(7! O(/9:9! / <!/9(-9! R!.4!69:6!/ .!/69!6(-46!77:6!Z[=!6!

0/9(/:0:7-?.0/(906! / 6!&:-9! Rh0&69?--00/9'!9!6Z =6 7 (%!7(!/!7

O6<(/!O[=74-! (/9'!!4( :6-74!9'60:&'%60/90-9!6-06!'0-!(/9'!7,:--

/ (/%-9! 7-0=-?R/ :9(0/0%6(/ !9'=70.4-!9! %9!6gd.(/:9!7/ 9'!4/!

9!790/%(6.! 6(/ !9'R:7!5:!/9-?O/!79'!7(=779044! / 9'!<!/9(-906=7

7=(9'! 90.(>0%iduf/ idu.! (-(6R0<!ld.. &=70/7( !6! 90

!/06.09!/7(<!R'!/ 6044! !-0=ld.. &OdRe,&W '? 60>?!9'?-796'70-:9(0/

Z X79!6(- eduO 6!7!/(:7 (O   0.:6&O !6./?[ / O (% /!!776?O dRde .&W.-

/06!4(/!4'6(/!=!6! .(/(79!6! R.>(.:.0%lddJ-0%%-:( =7 .(/(79!6!  :6(/&h

'0:670%6(/ !9'R-:(  .(/(7969(0/=70.46-!(/--&60:47Z-!e[R-00 O:6(/!

/ ,( /!?7=!6!'6<!79! %9!6h'0:670%6(/ !9'R ( /!?7=!6!!.! ! (/46%%(/

067/4X%60@!/(/-(5:( /(960&!// 90&!9'!6=(9'9'!7!6:./ :6(/!7906! 9XldER'.X 04!69!  697 :/ !6=!/9 9'! 7.! 7:6&(- 460! :6!O :9 =(9'0:9 9'! (/7!69(0/ 0% 9'!

--00/9'!9!6O/ 0/-?6!!(<! 7-(/!R'.X04!69! 697=!6!<!/9(-9! %06gd.(/:9!7

:/ !6/!79'!7(=(9'.(>9:6!0%fRiu(70%-:6/!/ eddufR%9!6gd.(/:9!7O7'.X 04!69! 697=!6!76(%(! R



" )"(#"

0(/<!79(&9!6!/-%:/9(0/O7!6:.6!9(/(/!-!<!-7=!6!.!7:6! 99'!9(.!0%76(%(!O

:7(/&0'!0 :-67?79!.Z0'!O7!-O=(9@!6-/ [R



"  #&$# #-

6%%(/ 7!9(0/7 Zh }.[ =!6! 79(/!  =(9' !6(0 ( ( X'(%% 79(/R (790-0&(- (/+:6?O

6!%-!9!  ? :9! 9::-!7 /!607(7 Z[ =7 !9!6.(/!  7!.(X5:/9(99(<!-? ? 9=0

07!6<!67:7(/&9'!%0--0=(/&706(/&7?79!.Qdx/0PexdXeduPfxedXfiuP

gxfiXidu/ hxziduR



559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager Processed on: 10-5-2021 Processed on: 10-5-2021 Processed on: 10-5-2021

Processed on: 10-5-2021 PDF page: 185PDF page: 185PDF page: 185PDF page: 185

 QXU

?90,(/!7%9!66(/ !9'R09-=7!>969! %60.%60@!/,( /!?7:7(/&9'!@0-

.!9'0  Z/<(960&!/O -9'.O [ /  7! .4-(%(9(0/ 6 ! Z!6,[O 06 (/& 90

./:%9:6!6T7(/796:9(0/7R!/0.(0/9.(/9(0/=7<!6(%(! ?X5:7(/&IX

9(/46(.!67O(/='('9'! (9(0/0%6!<!67!96/76(497!=70.(99! R



'-"(''"%

7?/9'!7(7=74!6%06.! ?9'! (9(0/0%dRi}-79!6(-!=9!6Oh}-i>%(679796/ :%%!6

46(.!67Z:44-!.!/96?-!e[R'!.(>9:6!=79'!/(/:9! %06id.(/:9!79gkER

%9!69'9O9'!6!<!67!96/76(497!=7(/9(<9! ?(/:9(/&9'!.(>9:6!9kdE%06ei

.(/:9!7R '! 5./ 44-(!  (07?79!.7 kmdd  X5 7?79!. Z(07?79!.7O 6-7 O

[=7:7! 90.4-(%?/  !9!9460 :97O:7(/&6!!/Z44-(! (07?79!.7O

079!6 (9?O [R X<-:!7 =!6! 066!9!  %06 8X9(/ /  &!/! !>46!77(0/ <-:!7 =!6!

!>46!77! 7fX||ZQ9'6!7'0- ?-![R



-7.4609!(/-!<!-70% Xj=!6! !9!6.(/! ?69!/@?.!X-(/,! (..:/0706!/977?

Z^ ?79!.7P idjO (/& 0/O >0/O  [R -- 7.4-!7 =!6! /-?@!  (/ :4-(9! /  .!7:6! 9/049(- !/7(9?0%hid/.R



:$#; Q PFQBU PBX PFQBU PBTWY

&))%# %:$#; PBRYU PFQBY PBRU PFRBXX PBYXY

:$$ ; QPP YPFQQP QPS WYFQQU PBWXW

/4$2$,+0A@$+2/.3/2$)/+"? @#7/,672#7)02/#0,)32$,+?@*+/2/$)

-/003/B

559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager Processed on: 10-5-2021 Processed on: 10-5-2021 Processed on: 10-5-2021

Processed on: 10-5-2021 PDF page: 186PDF page: 186PDF page: 186PDF page: 186

 QXV

8 

9g  =74!6%06.! O7 !76(! 46!<(0:7-?O90.!7:6!0.4-!.!/99(<9(0/

%9!6h'0:670%6(/ !9'R /6(!%O69g =749:6! =(9'.0/0-0/-.0:7!/9(X

g/9(0 ?Z7XflfmhO/9(6:@OO[R6(9/9(X':./g =7:7! 7 !9!9(0/

/9(0 ?Z,0[/ &09/9(X6(9X Z,0[=(9'gOgTOiOiTX!96.!9'?-!/@( (/!Z[

X-:!77:7969!R.4-!(/:9(0//  !9!9(0/79!47=!6!4!6%06.! %06jd.(/:9!79

gkER!%06!g =7.!7:6! O--7.4-!7=!6!40-?!9'?-!/!&-?0-Z[46!(4(99! R

46!(4(99(0/(76!5:(6! 7(/!%6!!g 7'6!7!4(904!7=(9'(/99gR--4-7.7.4-!7

=!6!eQe (-:9! =(9'ffu(/dRe069!W:%%!6Z4 lRgf[R.4-!7=!6!(/:9! 

%06 g '0:67 0/ (! /  7:7!5:!/9-? !/96(%:&!  %06 ed .(/ 9 hddd 64. 9 hER '!/O

7:4!6/9/97=!6!0--!9! / :7! %06g 5:/9(%(9(0/R79/ 6 :6<!=7. !

:7(/&@?.07/X9(<9! 400-! 694-7.R

'!.0:/90%g (/9'!7.4-!7=7 !9!6.(/! %60.9'!79/ 6 :6<!/ !>46!77! (/

6(966?:/(97W.-R.4-!7=!6!/-?@! (/ :4-(9!/ .!7:6! 9/0%hid/.

ZXgOehfd.:-9(-!-0:/9!6O!6,(/-.!6O-9'.O[R



!!)"#'(#!'(&-

%60@!/7!9(0/7Zh}.[%(>! (/!90/!R..:/0'(790'!.(796?%06,( /!?(/+:6?.0-!:-!Xe

Z Xe[ /  .604'&!7 ZXe[ =!6! 4!6%06.!  0/ %06.-(/X%(>! O 46%%(/X!.! !  7!9(0/7R6%%(/7!9(0/7Zh}.[=!6! !46%%(/(@! O6!'? 69! O/ /9(&!/76!96(!<! ?

0(-(/&9'!7!9(0/7%06gd.(/:9!7(/dReW -Z4 m[R--7!9(0/7=!6!-0,! =(9'

'? 60&!/4!60>( 7!%06gd.(/:9!7/ (/:9! =(9'9'!46(.6?/9(0 ?%06e'0:69

600.9!.4!69:6!Z-!f[R%9!6=7'(/&=(9'4'074'9!:%%!6! 7-(/!Z[O9'!7-( !7

=!6! (/:9!  =(9' 9'! 446046(9! '067!6 (7' 4!60>( 7!X0/+:&9!  7!0/ 6? /  9!69(6?/9(0 (!7Z,0O64(/9!6(O[(/eu70-:9(0/%06gd.(/:9!7R'!6!9(0/

=7 !<!-04! ? (9(0/0%gX.(/0XmX!9'?-6@0-!ZP,0[06gOgX (.(/0!/@( (/!

ZP !6,O 6.79 9O !6./?[ /  gdu R !9(0/7 =!6! 0:/9!679(/!  =(9'

'!.90>?-(// !.! ! (/5:9!>.0:/9(/&&!/9Z!6,[R065:/9(99(<!!<-:9(0/

0% hl/ Xe(/9'!6!/-069!>Ohd7/47'0970%9'!6!/-069!>=!6!9,!/%60.9'!

!'.6,!6=!6!9'!/0:/9! :7(/&4!6(0.&!04!/-?7(70%9=6!Z0+!9(<!id>X fdd>[Z !((07?79!.7O(79OO[Rg OiXm/  Xe7!9(0/7=!6!706! 7!.(X 5:/9(99(<!-??9=007!6<!679.&/(%(9(0/0%fd>Rg / iXm=!6!706! ?9'!

%0--0=(/&706(/&7?79!.Qdx/079(/(/&PexdXfiuPfxfiXiduPgxidXkiu/ hxkiXeddu

!>46!77(0/(/9'!069(-9::-!7R Xe=7706! 4!6%(!- O7 !76(! ?</(..!6!/

  /6(!%Odx/079(/(/&OtxdXefRiuOexefRiXfiuOfxfiXiduOgxidXkiuOhxkiX edduR





559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager Processed on: 10-5-2021 Processed on: 10-5-2021 Processed on: 10-5-2021

Processed on: 10-5-2021 PDF page: 187PDF page: 187PDF page: 187PDF page: 187

 QXW

9!79=7:7! 900.46!9'! (%%!6!/!7!9=!!/9=0&60:47R0/%!660/(066!9(0/=7

:7! 900:/9%06.:-9(4-!0.46(70/7R--799(79(-9!797=!6!fX9(-! / 4X<-:!-!77

9'/ dRdi =7 0/7( !6!  7(&/(%(/9R 0/X46.!96( 9 6! 46!7!/9!  7 .! (/ {

(/9!65:69(-!6/&!/ 46.!96( 96! (74-?! 7.!/{79/ 6  !<(9(0/Z[R



C9G /,8+ ,30*,+,),+)+2$F/2

**/+22(,*-)6

559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager Processed on: 10-5-2021 Processed on: 10-5-2021 Processed on: 10-5-2021

Processed on: 10-5-2021 PDF page: 188PDF page: 188PDF page: 188PDF page: 188

 QXX

') ('

&(!"(+("(2(#&$&*"(#('-'(!" # #!$ !"((*(#""

&('')((#&"(

0(/<!79(&9!='!9'!69'!0.4-!.!/97?79!.(79(<9! (/0:6696(/ !9'.0 !-O=!

!9!6.(/! 7?79!.(/ -0-0.4-!.!/99(<9(0/-!<!-7%9!6h'0:670%6(/ !9'R

?79!.( g  -!<!-7 =!6! 7(&/(%(/9-? (/6!7!  %9!6 9'! (/ :9(0/ 0% 6(/ !9' ='!/

0.46! 907'.X04!69! 697O='('(/ (9!79'99'!0.4-!.!/97?79!.=7(/ !! 

9(<9! :40/6(/ !9'Z(&:6!f[R



 ,)@70*+$ %#&#&$'#$%+#-#*+)B&,)*&) %+7 

HI702*$S)4)0,!/$+F/202/25$2#0)$+,/+2$F!2,/B)0*S)4)05/

2/*$+!2/T#,3/0,!/$+2#BS50-23/730$+"*,+,),+)*,30+2$FS

+2$,7?225$2#/$2+2$F#3*+S+2$,7+",2+2$F/$2F BHI/+)UFY

-,0$2$,++HI/+)S-,0$2$,+$+!/,8+02$,+0!/,*HI0#*F,-/2/20?0)$+F2/2

/20++2$F!2,/2/2/20!2/T#,3/0,!/$+2#B2/0#,5+0*$+_B2

50+)78730$+"++#$2+7F202+,+!//,+$-,02F#,202?02/$0(0,42#/0

+,2 0$"+$!$+2 $!!/+0 25+ 2# /$+F /20B HJ-^PBPU@ JJ-^PBPQ@ JJJ-^PBPPQIB #

0# )$+ /-/0+20 2# *+ ,! 2# 0#*F,-/2 /20B M $+$2 0$"+$!$+2 $!!/+0

25+2#/$+F/20 0#*F,-/2/20HM-^PBPU@MM-^PBPQ@MMM-^PBPPQIB

559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager Processed on: 10-5-2021 Processed on: 10-5-2021 Processed on: 10-5-2021

Processed on: 10-5-2021 PDF page: 189PDF page: 189PDF page: 189PDF page: 189

 QXY

!>9O=!77!77! ='!9'!696!9.!/9=(9'/9(X=7-!9046!<!/97?79!.(0.4-!.!/9

9(<9(0/(/697R6!96!9.!/9=(9'/9(X46!<!/9! 0.4-!.!/99(<9(0/7(&/(%(/9-?O

7'0=/ ? 6! :! g  -!<!-7 0.46! 907-(/!X96!9! 697Z(&:6!f[R / (9(0/O=!

!9!6.(/! ='!9'!696!9.!/9=(9'/9(X-! 90-!77-0-0.4-!.!/99(<9(0/R'!6!

=7/07(&/(%(/9(/6!7!(/iXm !407(9(0/%9!6h'0:670%6(/ !9'0.46! 907'.X 04!69! 697Z(&:6!f[R 0=!<!6O6!/-g  !407(9(0/=77(&/(%(/9-?(/6!7! (/6(/X ! 6970.46! 907'.X04!69! 697Z(&:6!f[R/ (9(0/O6(/X ! 69746!96!9! 

=(9' /9(X '  7(&/(%(/9-? -!77 g  !407(9(0/ 9'/ 7-(/!X96!9!  697 Z(&:6! fX[R

<!6--O/9(X7(&/(%(/9-?46!<!/9! 09'7?79!.(/ -0-0.4-!.!/99(<9(0/0/9'!

-!<!-0%g%9!6h'0:670%6(/ !9'R



"(2(#&$&'&*'&" )"(#""((")('&" ")&-(&&"(

0 !9!6.(/!='!9'!696!9.!/9=(9'/9(X=7-!9046!7!6<!6!/-%:/9(0// 4609!9

&(/796!/-(/+:6?O=!.!7:6! 7!6:.6!9(/(/!-!<!-7O706! %06'(790-0&(-(/+:6?/  (/<!79(&9! ,( /!?(/+:6?.0-!:-!XeZ Xe[-!<!-7(/9'!,( /!?R(679O4-7.6!9(/(/!

-!<!-7=!6!7(&/(%(/9-?!-!<9! (/6(/X ! 6970.46! 907'.X04!69! 697Z(&:6!

g[R 6!96!9.!/9 =(9' /9(X 46!7!6<!  6!/- %:/9(0/O 6!%-!9!  ? 7(&/(%(/9-? -0=!6

7!6:.6!9(/(/!-!<!-79'/7-(/!X96!9! 697%9!66(/ !9'Z(&:6!g[R 0=!<!6O7!6:.

6!9(/(/!-!<!-7(//9(X96!9! 697=!6!79(--7(&/(%(/9-?'(&'!69'/(/7'.X04!69!  697R!0/ O/9(X96!9! 697' 7(&/(%(/9-?-!776!/-(/+:6?9'/7-(/!X96!9! 6(/X ! 697O !.0/7969! ?-0=!6-!<!-70%6!/-9::-6/!607(7Z(&:6!g[R'(6 O.

!>46!77(0/0% XeO4609!(/='('(7.(/-?!>46!77! 0/ .&! 6!/-!4(9'!-(-!--7 O

=7 7(&/(%(/9-? :46!&:-9!  (/ 6(/X !  697 0.46!  90 7'.X04!69!  697R

6!96!9.!/9=(9'/9(X6!7:-9! (/7(&/(%(/9-?-0=!6 Xe&!/!!>46!77(0/-!<!-7O='('

(/ (9!76! :9(0/(/6!/-9::-6 .&!Z(&:6!g[R 79-?O=!/-?@! 6!/- Xe

!407(9(0/?4!6%06.(/&(..:/0'(790'!.(796?R6(/X ! 697' 7(&/(%(/9-?.06! X e4609!(/ !407(9(0/(/9'!460>(.-6!/-9::-!79'/7'.X04!69! 697R%9!66(/ !9'O

Xe79(/(/&=746(.6(-?7!!/(/9'!069(0.! :--6?+:/9(0/R/9(X96!9! 697'  7(&/(%(/9-? -!77 Xe !407(9(0/ 9'/ 7-(/!X96!9!  697 Z(&:6! gX[R ,!/ 90&!9'!6O

9'!7! 9 7'0= 9'9 46!96!9.!/9 =(9' /9(X 46!7!6<!  6!/- %:/9(0/ /  99!/:9! 

6(/ !9'X(/ :! 6!/-(/+:6?R



8

559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager Processed on: 10-5-2021 Processed on: 10-5-2021 Processed on: 10-5-2021

Processed on: 10-5-2021 PDF page: 190PDF page: 190PDF page: 190PDF page: 190

 QYP

 

























 ,)A7%#,%+ &%%)%# %!,)0,'&%) %+. +*# %&)%+ 9+&)7

HI+)!3+2$,+/!)27-)0*/2$+$+)4)0,!/$+F/202/25$2#0)$+,/+2$F

,*-/2,0#*F,-/2/20B/3*/2$+$+)4)05/*03/22$*,!0/$!$BHI

33)/*"50/!)20-/+2",!32233)/+/,0$0$+2#/+),/26BHI+)

FQ "+ 6-/00$,+ $+ /$+F + 0#*F,-/2 /20 2/2 5$2# 0)$+ ,/ +2$F 50

2/*$+7.3+2$22$4/)F2$*B#*6-/00$,+,! FQ/)2$42,<F2$+5002

2Q$+0#*F,-/2/20?2#,2#/4)30/)3)2,/$+")7BHI+) FQ-,0$2$,+

Q-/!$)BHI FQ-,0$2$,+$+0#*F,-/2/20?$+0)$+F2/2/20+$++2$F2/2

/20B 2 / 0#,5+ 0 *$+ _ B 2 50 +)78 7 30$+"  ++ #$2+7F 202 +

,+!//,+$-,02F#,202?J,42#/0+,20$"+$!$+2$!!/+025+2#/$+F/20B

HJ-^PBPU@JJ-^PBPQIB#0#)$+/-/0+202#*+,!2#0#*F,-/2/20BM$+$2

0$"+$!$+2$!!/+025+2#/$+F/20 0#*F,-/2/20HM-^PBPU@MM-^PBPQ@

MMM-^PBPPQIB

 







   

   

559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager Processed on: 10-5-2021 Processed on: 10-5-2021 Processed on: 10-5-2021

Processed on: 10-5-2021 PDF page: 191PDF page: 191PDF page: 191PDF page: 191

 QYQ

"(2(#&&)''-'(! 2; * '",$&''#" * '#$&#2" !!(#&-"'

"("-

077!77='!9'!60.4-!.!/9(/'((9(0/=(9'/9(X(/%-:!/!76(/ !9'X(/ :! 6!/-

-!<!-7=!6!7(&/(%(/9-?'(&'!6(/7-(/!X96!9! 6(/X ! 6979'/(/7'.X04!69! 697

Z(&:6! hO 4ydRdde[R 6!96!9.!/9 =(9' /9(X 46!<!/9!  9'! (/6!7! 0% 7?79!.( Xj

7(&/(%(/9-?0.46! 907-(/!X96!9! 697%9!66(/ !9'Z(&:6!hO4ydRdi[R!>9O=!

!9!6.(/! 6!/-.-!<!-70%.:-9(4-!460X(/%-..906?&!/!7R%9!6h'0:670%6(/

XeO'!.0,(/!Xe/ 404907(769(0W-Xf=!6!--7(&/(%(/9-?:46!&:-9! 

0.46! 907'.X04!69! 697Z(&:6!hX [R'!7! 9 !.0/7969!9'90:6696(/

!9'.0 !-.(.(79'!(/+:6?7!!/(/':./6(/X !  0/067R 9796!9! =(9'/9(X

7'0=! 7(&/(%(/9-?-0=!6&!/!!>46!77(0/70%460X(/%-..906??90,(/! XjZ(&:6!hXO

4ydRde[R!7( !7O6!/-&!/!!>46!77(0/-!<!-70%Xe/ Xe=!6!7(&/(%(/9-?-0=!6

(//9(X96!9! 6979'/(/7-(/!X96!9! 697%9!6h'0:670%6(/ !9'Z(&:6!hXO

7(&/(%(/9-?Z(&:6!hX[R6!9.!/9=(9'/9(X ( /096! :!9'!404907(769(0W-X f(/9'!,( /!?:40/6(/ !9'Z(&:6!h [R-90&!9'!6O9'!6!7:-97 !.0/7969!9'9/9(X

99!/:9!79'!460X(/%-..906?6!740/7!:40/6(/ !9'R



 

 

8

559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager Processed on: 10-5-2021 Processed on: 10-5-2021 Processed on: 10-5-2021

Processed on: 10-5-2021 PDF page: 192PDF page: 192PDF page: 192PDF page: 192

 QYR

 ,)B7)&9 %#$$+&)0%/')** &%#-#* %+" %0+)B&,)*&) %+7

HI702*$ FV)4)0,!/$+F/202/25$2#0)$+,/+2$F,*-/2,0#*F,-/2

/20!2/T#,3/0,!/$+2#B/2+87*F)$+($**3+,0,/+20072/*$+-)0*)4)0

,! FVB))0*-)05/+)78$+3-)$2+*03/2+,!TUP+*B/,F$+!)**2,/7

"+ 6-/00$,+0 $+ 2# ($+70 ,! /$+F /20 2/2 5$2# 0)$+ ,/ +2$F!2,/ B *

/2$,B2/0#,5+06-/00$,+/)2$42,<F2$+0022Q$+0#*F,-/2/20?2#,2#/

4)30/)3)2,/$+")7B2/0#,5+0*$+_B250+)78730$+"++

#$2+7F202+,+!//,+$-,02F#,202?02/$0(0,42#/0+,20$"+$!$+2$!!/+0

25+2#/$+F/20HJ-^PBPU@JJ-^PBPQIB#0#)$+/-/0+202#0#*F,-/2/20B

M$+$20$"+$!$+2$!!/+025+2#/$+F/20 0#*F,-/2/20HM-^PBPU@

MM-^PBPQ@MMM-^PBPPQIB





&(!"(+("(2(#&&)'(" ),#!&#$'(&9#)&'#&"

(

0 0.4-!9! 9'! 6!/- (/%-..906? 460%(-!O =! !9!6.(/!  9'! (/%-:> 0% /!:9604'(-7 /  .604'&!7 ? (..:/0'(790'!.(796?R %9!6 h '0:67 0% 6(/ !9'O 9'! /:.!6 0%

.604'&!7 ZXe[ /  /!:9604'(-7 Z hl[ (/ 9'! ,( /!? =!6! 7(&/(%(/9-? (/6!7!  (/

6(/X ! 6970.46! 907'.X04!69! 697R!>9O=!(/<!79(&9! 9'!!%%!90%/9(X

0/9'!(/%-:>0%-!:,0?9!7(/9'!,( /!?R/6(/X ! 697O96!9.!/9=(9'/9(X-! 90

7(&/(%(/96! :! /:.!60%.604'&!79'/(/7-(/!X96!9! 697Z(&:6!iXO4ydRde[R

/  (9(0/O 9'! 70-:9! /:.!6 0% /!:9604'(-7 =7 -0=!6 (/ /9(X 96!9!  697 9'/ (/

7-(/!X96!9! 697Z(&:6!iX [R/0/-:7(0/O46!96!9.!/9=(9'/9(X7!!.79099!/:9!

9'!(/%-:>0%(/%(-969(/&-!:,0?9!7O!74!(--?.604'&!7O(/9'!,( /!?:40/6(/ !9'R





559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager Processed on: 10-5-2021 Processed on: 10-5-2021 Processed on: 10-5-2021

Processed on: 10-5-2021 PDF page: 193PDF page: 193PDF page: 193PDF page: 193

 QYS

 

 ,)C7% #+)+#,"&0+* %+" %0+)) %+ %*# %&)%+ 9+&)+)+)+*7

+!$)2/2)3(,720$+($+70,!0#*F,-/2+/$+F/202/25$2#0)$+,/+2$F

!2,/BHI+)+32/,-#$)$+!)36500,/$+!/,8+02$,+0!/,*HI0#*F,-/2/20?HI

/$+F /20 2/2 5$2# 0)$+ ,/ HI /$+F /20 2/2 5$2# +2$F!2,/ B HI +)

*/,-#"$+!)36500,/$+-/!!$+F*02$,+0!/,*HI0#*F,-/2/20?HI/$+F

/202/25$2#0)$+,/H I+2$F!2,/B2$,+05/.3PV+2$!$!,/2#+3*/,!-,0$2$4

/-/0+22RPP6*"+$!$2$,+B2/0#,5+0*$+_B250+)78730$+"

++ #$2+7F 202 + ,+!//,+$ -,02F#, 202? 02/$0(0 ,4 2# /0 +,2 0$"+$!$+2

$!!/+025+2#/$+F/20HJ-^PBPUIB#0#)$+/-/0+202#0#*F,-/2

/20BM$+$20$"+$!$+2$!!/+025+2#/$+F/20 0#*F,-/2/20

HM-^PBPU@MM-^PBPQIB 

8

559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager Processed on: 10-5-2021 Processed on: 10-5-2021 Processed on: 10-5-2021

Processed on: 10-5-2021 PDF page: 194PDF page: 194PDF page: 194PDF page: 194

 QYT

')''#"

/9'(779: ?O=!(/<!79(&9! ='!9'!6(/'((9(0/0%%906/99!/:9!6(/ !9'X(/ :!  6!/-(/+:6?/ (/%-..9(0/(/697R0'(!<!9'(7O=!46!96!9! 697=(9'.0/0-0/-

/9(0 ?&(/79%906Z/9(X[/ 7:7!5:!/9-?7:+!9! 9'!69790h'0:670%6(/

!9'R ! %0:/  9'9 /9(X 46!7!6<!  6!/- %:/9(0/O 6! :!  6!/- (/+:6? /  6!/-

(/%-..9(0/(/6(/X ! 697R(679O=!79: (! 9'!!%%!90%/9(X96!9.!/90/7?79!.(

/ -0-0.4-!.!/99(<9(0/R!07!6<! 7(&/(%(/9-?-0=!64-7.-!<!-70%g (//9(X

 96!9!  697 9'/ (/ 7-(/!X96!9!  697 %9!6 h '0:67 0% 6(/ !9'R '!7! 6!7:-97

!.0/7969!9'996!9.!/9=(9'/9(X-! 790-!777?79!.(0.4-!.!/99(<9(0/O='('

.(&'9!(.4069/9!:7!'(&'7?79!.(0.4-!.!/9-!<!-7(/9'! 0/066!770(9! =(9'

:9!6!+!9(0/0%':./6!/---0&6%97R / (9(0/O9'!46!7!/979: ? !.0/7969!79'9

46!96!9.!/9=(9'/9(X6!7:-9! (/7(&/(%(/9-?-!77-0-0.4-!.!/9g  !407(9(0/R%

(.4069/!O 7(/! 46!<(0:7 79: (!7 '<! 7'0=/ 9'9 6!/- 0.4-!.!/9 g 7?/9'!7(7 (7

770(9! =(9':9!6!/-96/74-/96!+!9(0// :9!4079X(7'!.(6!/-%(-:6!R  

!>9O=!(/<!79(&9! 9'!!%%!90%96!9.!/9=(9'/9(X0/6!/-%:/9(0// 6!/-

(/+:6?%9!6h'0:670%6(/ !9'R6!9.!/9=(9'/9(X46!7!6<! 6!/-%:/9(0/(/6(/X !  697R 0=!<!6O 7!6:. 6!9(/(/! -!<!-7 (/ /9(X 96!9!  697 =!6! 79(-- '(&'!6 9'/

6!9(/(/! -!<!-7 .!7:6!  (/ 7'.X04!69!  697R !  76(!  9'! 7!  7.-- (%%! 6! /! 7 (/

7!6:.6!9(/(/!-!<!-7909'!'!.0 ?/.('/&!77!!/ :6(/&6(/ !9'O='('=!6!/09

7!!/(/7'.X04!69! 697R'!6!%06!O6977:+!9! 906(/ !9'6!!(<! .06!%-:( 9'/

7'.X04!69!  697O ='(' !>4-(/7 9'! 07!6<!  (%%!6!/!7 (/ 4-7. 6!9(/(/! -!<!-7

!9=!!//9(X96!9! 697/ 7'.X04!69! 697Z-!e[R/ (9(0/O=!07!6<! /

!  697R (.(-6 07!6<9(0/7 =!6! 0/! ? (+0!6   O ='0 7'0=!  9'9 Xe (7

7:79/9(--? :46!&:-9!  (/ ':./ 6(/X !  0/067R  '! %9 9'9 09' Xe &!/!

!>46!77(0/ -!<!-7 /  Xe !407(9(0/ =!6! 6! :!  (/ /9(X 96!9!  697 7!!.7 90 !

(.4069/97(/! Xe(7,/0=/90!/(/ !4!/ !/946! (9(<!.6,!6%066!/-%:/9(0/(/

6!(4(!/97%9!66!/-96/74-/99(0/R 79-?O7(/!=!07!6<! 9'996!9.!/9=(9'/9(X

-!  90 -0=! 6 &! /!  ! >46! 77(0/ -! <! -7 0% XjO Xe /  Xe %9!6 6(/ !9'O (9 (7

7:&&!79!  9'9 /9(X 6! :!7 6(/ !9'X(/ :!  6!/- (/%-..9(0/R /9!6!79(/&-?O 697

j-!<!-70:- !!>4-(/! ?9'!%99'9/ %6&.!/97'<!<6(!9?0%(0-0&(-

9(<(9(!7(/ !4!/ !/90%9'!4609!0-?9(9(<(9?R /(.4069/9-(.(99(0/0%9'(779: ?(7

9'!%99'9/9(X=7/09 .(/(79!6! %9!69'!0/%(6.9(0/0%6(/ !9'R/9(X=7

 .(/(79!6! fd.(/:9!7!%06!9'!0/%(6.9(0/0%6(/ !9'O='('(7(.4077(-!906!-(@!

(/-(/(-469(!R'!6!%06!O9'(779: ?7!9X:47!6<!774600%0%46(/(4-!90(/<!79(&9!

9'!!%%!90%/9(X0/6(/ !9'X(/ :! 6!/-(/+:6?(/697R06!6!7!6'(7/!! ! 90

!<-:9!9'!!%%!90%/9(X :6(/& (%%!6!/99(.!40(/979'60:&'0:99'!6(/ !9'4!6(0 R

/9'!:66!/979: ?O=! ( /09(/-: !&60:4=(9'/9(X .(/(7969(0/%9!69'!(/ :9(0/

0%6(/ !9'R'!049(.-9(.!40(/90%(/9!6<!/9(0/=0:- !!9=!!/gdXmd.(/:9!7%9!6

9'!(/ :9(0/0%6(/ !9'O='('-!<!70/-?fXg'0:6790!<-:9!9'!!%%!90%/9(X

559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager Processed on: 10-5-2021 Processed on: 10-5-2021 Processed on: 10-5-2021

Processed on: 10-5-2021 PDF page: 195PDF page: 195PDF page: 195PDF page: 195

 QYU

96!9.!/90/6!/-(/+:6?(/0:66(/ !9'.0 !-%06697R!0/7( !69'(79007'069O7(/!

9'!.>(.:.!%%!90%/9(X96!9.!/9(7446!/9%9!6h'0:67R '!6!%06!O=!0/7( !6

(97/!>979!490(/<!79(&9!9'!!%%!90%/9(X96!9.!/9%9!69'!(/ :9(0/0%6(/ !9'

(/-6&!6/(.-.0 !-%066(/ !9'R/09'!6-(.(99(0/0%9'(779: ?(79'9=!0/-?:7!  .-!697O90(6:.<!/97!>X6!-9!  (%%!6!/!7(/0.4-!.!/9-!<!-7/ %:/9(0/-(9?R 

 79: ? 4!6%06.!  ? ':6./    -6! ? !.0/7969!  9'! 409!/9(- 0%

0.4-!.!/9%906(/'((9(0/(/.0:7!.0 !-0%6!/-(7'!.(X6!4!6%:7(0/(/+:6?R/

(/'((906?.0/0-0/-/9(0 ?90.0:7!%906=7:7! O='('7(&/(%(/9-?46!7!6<!  6!/-%:/9(0// -! 90-!776!/-(/+:6?R':7O%9067!!.790!460.(7(/&96&!990

(.460<!6!/-96/74-/90:90.!O(/09'9'! 0/067=!--7(/9'!6!(4(!/9R 0=!<!6O

96!9.!/90%9'! 0/06.(&'9!.06!!/!%((-9'/0%9'!6!(4(!/9O7(/!9'!0.4-!.!/9

7?79!.(7-6! ?9(<9! (/9'! 0/06/ 7'7!!/7'0=/90%%!99'!%:/9(0/0%9'!

6!/- --0&6%9R   ,!/ 90&!9'!6O 9'!7! 6!7:-97 6!9!  /!= =(/ 0= 0% 044069:/(9? %06

0.4-!.!/9X96&!9! 9'!64(!7(/9'!6!/-96/74-/99(0/7!99(/&R 0=!<!6O='!/96!9(/&

9'! 0/06O(97'0:- !0/7( !6! 9'9--06&/7=(--!96!9! =(9'9'!7.! 6:&/ 7.!

07! 0% 96!9.!/9R '(-! 0:6 79: ? 7'0=7 9'9 9'! 5:-(9? 0% 9'! ,( /!? (.460<!7 %60.

96!9.!/9=(9'/9(X(/9'! 0/06O9'(7(7/09?!9(/<!79(&9! %069'!09'!606&/7R7!  0/-(9!69:6!O9'!'!69.?-70!/!%(9%60.96!9.!/9=(9'/9(XR':/ 7'0=! 9'9

7?79!.(-!<!-70%%906(/09'.(!/ ':./6!407(9(<!-?066!-9! =(9'.?06 (-

/!607(7%9!66 ((7'!.(X6!4!6%:7(0/(/+:6?R/ (9(0/O7!/!0%%9066!7:-9! (/

7(&/(%(/9.?06 (-4609!9(0/%9!66 ((7'!.(X6!4!6%:7(0/(/+:6?R -9'0:&'-!77(7

,/0=/0:9%906(/09'!606&/7 :6(/&96/74-/99(0/O%906'7!!/ !76(! 90

4-?4(<09-60-!(/.:-9(4-!460X(/%-..906? (7!7!.0 !-7O7:'76!9(/-(/+:6?/ 

69'6(9(7R-90&!9'!6O9'!7!407(9(<!%(/ (/&76!7:-9! (/9'! !<!-04.!/90%9'!64!:9(

96&!97&(/79%906R

:66!/9-?O9=0 6:&79'9/(/'((9%9066!9!79! (/-(/(-96(-7R/!0%9'!.

(7 dfgO7.--.0-!:-!9'9(/ 79'!9(<!7(9!0%%906R dfg(7:66!/9-?9!79! (/

 !!/9-?O 0/(7

 (/ 49(!/97 =(9' &!X6!-9!  .:-6 (7!7!R 6(0:7 &!/97 9'9 96&!9 %906  6! 

:66!/9-?:/ !6 !<!-04.!/9O%06!>.4-!7(&(/79%906Z-/?-.[R'!7!96(-7O

.?700/-! 909'!-(/(-<(-(-(9?0%0/!06.06!0.4-!.!/9(/'((90679'996&!9

%906R

/0/-:7(0/O=!7'0=9'9/9(X46!96!9.!/9(/6(/X !  0/0669746!7!6<!7

6!/-%:/9(0// 4609!97&(/796!/-(/+:6?/ 6!/-(/%-..9(0/R'!6!%06!O/9(X

96!9.!/9.(&'9!409!/9(-9'!64?906! :!6(/ !9'X(/ :! 6!/-(/+:6?46(0690

96/74-/99(0/R



 

8

559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager Processed on: 10-5-2021 Processed on: 10-5-2021 Processed on: 10-5-2021

Processed on: 10-5-2021 PDF page: 196PDF page: 196PDF page: 196PDF page: 196

 QYV

 



,''#$%+)0#?7



%9*'  (') $)*7





) $)*





) $)*(,%*



$'#  + &%#%+

<F2$+ UdFFSd

UdFFSd WT

 UdFFSd

UdFFSd WT

)FR UdFFSd

UdFFSd WP

FQ< UDFFSD

SDFFUD QPV

FV UdFFSd

UdFFSd XY

FQX UDFFSD

UDFFS VR

FQ UdFFSd

UdFFSd WU

FQ UdFFSd

UdFFSd WX

F0)2$+ UdFFSd?

UdFFSd XP

FQ UdFFSd

UdFFSd XT

/4$2$,+0A<F2$+?<2F2$+@?)FRF00,$2-/,2$+@)FR?F)))7*-#,*-/,2$+

FQ?403)/))#0$,+*,)3)FQB

559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager Processed on: 10-5-2021 Processed on: 10-5-2021 Processed on: 10-5-2021

Processed on: 10-5-2021 PDF page: 197PDF page: 197PDF page: 197PDF page: 197

 QYW

8

&"'

^J :7197/85-/9/9"7/9(1/-1:/!9(1/J7&/897/85-/9"!(/--G@@"7G@!1/179@5"G@

17&/J:-(8'"!_]^dJ "88"!"59"."7^G_]_]J'9958INN>>>J":7197/85-/9J17&N899(89( 8N

_J 18G ":="/(/, G/117 G-1"& J (!/"@&7%98%71.7(/!"!!1/178I/%"7(176:-(9@17

155179:/(9@%17(.571="."/9F %/%*J_]]dHd_UdVIdfdQe]bJ!1(I^]J^]`eN8+J,(Jb]]_a]]

`J 799 G8'""7G ,8 J 1 -8@/9'"8(81% 1.5-"."/9 1.51/"/9`7"&:-9"8 :9"7"/-

97/85-/97"+" 9(1/J*J_]]_HeUcVIbe_QbedJ!1(I^]J^]`eN/.]c]_Qbe_

aJ "&-G:!7( (G9"-G"9-J".7/"99 ,@ 1.5-"."/9I9'"88".-@/!(1-1&@1%

9"7.(/- 1.5-"."/9 1.5-"?"8J$$+%&#)J_]^^Hb^U^VIabQc]J!1(I^]J^]]dN8^_]_cQ]^^Qe_`fQb

bJ -5179 J1.5-"."/9Q%(7891%9>15798J%# J_]]^H`aaI^]beR^]ccJ

cJ -5179 J1.5-"."/9J" 1/!1%9>15798J ,@G18"/G"!8J%# J

_]]^H`aaU^bVI^^a]Q^^aaJ!1(I^]J^]bcN _]]^]a^_`aa^b]c

dJ ../ G'G/1/ G ":="/(/, G-1"& G""-"/J71889-,"9>""/ 1.5-"."/9

/!91--Q-(,"7" "5917 9(=9(1/(/7"-9(1/91!1/177(/!"9'/!7"/-(8 '".(Q7"5"7%:8(1/(/+:7@J

$ (%)'#%*J_]^^H^^UaVIcc]QccfJ!1(I^]J^^^^N+J^c]]Qc^a`J_]^^J]`adbJ?

eJ 155"-78G""-"/J1.5-"."/9Q."!(9"!(/%-..9(1//!(/+:7@(/7(/!"!17&/!1/178J

&#$$+%&#J_]^dHeaUeaVIddQe`J!1(I^]J^]^cN+J.1-(..J_]^cJ^^J]]a

fJ ../ G(+1"7G '::78G"9-J 1 -7"/- 1.5-"."/9`(/!: 9(1/@!1/177(/!"9'(8

881 (9"!>(9'7"!: "!7"/---1&7%9%:/ 9(1/%9"797/85-/99(1/J'(&# #(%)'#%*J

_]^^H_cUdVI_`abQ_`baJ!1(I^]J^]f`N/!9N&%6d^d

^]J ../ G""-"/G1"78G"9-J@89".(  1.5-"."/9 9(=9(1/(/!" "8"!!1/178(8

881 (9"!>(9' :9"7"+" 9(1/%9"77"/-97/85-/99(1/(/9'"7" (5("/9J(%)'#%** &%J

_]^^Hf_U_VI^c`Q^cfJ!1(I^]J^]fdNJ]]^`"`^e___ f]

^^J =/"7,'1="/G../ G/(+,G"9-J1.5-"."/9."!(9"!7"/-(/%-..9(1/

(/!: "!@!1/177(/!"9'I1-"1%7"/-bQb(/9"7 9(1/J$ (%)'#%*J_]^`H^`UaVIedbQ ee_J!1(I^]J^^^^N+9J^_^`]

^_J @!189G155"-78G=/ 119"/G"9-J&"/!"?Q881 (9"!'/&"81%1.5-"."/9

 9(=(9@/!1.5-"."/9 "="-8(/ "-9'@: 8(/15:-9(1/J(&%*$$+%&#J_]^eHfI_ccaJ

!1(I^]J``efN%(..:J_]^eJ]_cca

^`J "8"/8G ( G(/& G"9-J?57"88(1/1%1.5-"."/91.51/"/98(%%"78"9>""/ (!/"@--1&7%98

%71. (=(/&/!" "8"!1/178J $&'(&#J_]]fH_]UeVI^e`fQ^eb^J

!1(I^]J^ce^NJ_]]e^^^^ab

^aJ :)8G179+!G891-!(G"9-J1="-/9(1!@&(/89 :./ 9179'9-1 ,8

17.9(1/1%9'"`71 1/="798"/!/'((981.5-"."/9 9(=9(1/(/(8"8"1!"-8J 

$$+%&#J_]^aH^f`U^^VIbbcdQbbdbJ!1(I^]Ja]afN+(..:/1-J^a]_]^`

^bJ 1-,"79  GK9 79G/(+,G99"/8 G-1"& G ":="/(/, J'"&7!:-1/8"97(/

!"9.1!"-I7"-"=/9.1!"-9189:!@17&/!1/9(1//!(98 1/8"6:"/ "81/9'"1:9 1."%9"7

97/85-/99(1/J % $J_]]dHa^U`c`VJ!1(I^]J^_beN]]_`cdd]dde^_e_eae

^cJ =/(.."7"/G=/!"/ ":="-G(--@G,,"7G=/117 G9"&"./J::-7,(!/"@(/+:7@

.1-" :-"Q^U Q^V(/':./7"/-!(8"8"J *&#J_]]dH_^_U_VI_]fQ_^dJ!1(I^]J^]]_N59'J_^db

^dJ ../ G 1"&"7G1/"8 '/8,"7 G"9-J7&"9(/& 1.5-"."/9 9(=9(1/(/7(/Q!"!!1/178

(.571="87"/-%:/ 9(1/%9"797/85-/99(1/J(%)'#$$+%&#J_]^^H_aUaVI_``Q_`dJ

!1(I^]J^]^cN+J97(.J_]^^J]`J]]^

^eJ =/"7 1"="/ G"7 1789 G1-".G"9-J%%" 981%7(/!"9'/!'".1!@/.( 899:81/

%:/ 9(1//!(..:/1-1&(  9(=9(1/1%9'"519"/9(-!1/17-(="7(/9'"79J%%+(J_]]]H_`_UcVIe]aQ e^`J!1(I^]J^]fdN]]]]]cbeQ_]]]^_]]]Q]]]]f

^fJ 777G'1:G (/G ,8 J 1 -"?97=8 :-7511-1%`(8!"9"7.(//91%5189(8 '".( 

 :9"7"/-%(-:7"J J_]]cH_]U_VI_^dQ__cJ!1(I^]J^]fcN%+J]bQadad 1.

_]J ../ G'G ":="/(/,  G"9-J881 (9(1/1% 1.5-"."/9`&"/"=7(/98>(9'7"/-

97/85-/91:9 1."1%!" "8"! 7!( !"!!1/17,(!/"@8J$ (%)'#%*J_]^_H^_U`VIcc]QcceJ

!1(I^]J^^^^N+J^c]]Qc^a`J_]^^J]`ee]J?

_^J

^dbfJ!1(I^]J^^^^N+J^c]]Qc^a`J_]]fJ]_d^`J?

__J (/G/&J (!/"@(/+:7@.1-" :-"Q^(/,(!/"@!(8"8"J% #J_]^cH`eU^]VI^bcdQ^bd`J

!1(I^]J^]e]N]eec]__J_]^cJ^^f`e^c



559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager Processed on: 10-5-2021 Processed on: 10-5-2021 Processed on: 10-5-2021

Processed on: 10-5-2021 PDF page: 198PDF page: 198PDF page: 198PDF page: 198

 QYX

_`J >(G"7:(G(8'(.G"9-J/">515919( 59'>@%179'" 1.5-"."/9% 917Q!"7(="!

%7&."/9J ##/) &#J_]]]H^ebU_VI_e]Q_f_J!1(I^]J^]]_N^]fdQacb_U_]]]^^V^ebI_i_e]IIQ ^`j`J]JH_Q 

_aJ 1-"78G':7./ J'"-9"7/9(="59'>@1% 1.5-"."/9(/!(8"8"I155179:/(9("8%17

_bJ 1-G1771>G."7(:8 J/!%7&."/981%% 917 9(=9(1/I7&."/9571!: 9(1/G

(1-1&( - 9(=(9("8G/"1"5(915""?57"88(1//!6:/9(99(1/(/ -(/( -8.5-"8J&$'#$%*%#$$J

^fefHcU`VI^dbQ_]aJ!1(I^]J^^bfN]]]ac`]f`

_cJ .(9'J7(/!"9'I(."%17/(/9"7/9(1/- 1/8"/8:8J( %)*J_]^_H^]eI(cQ(fJ

!1(I^]J^]f`N+N"7`bb

_dJ 19(. G -7Q1'..!G:"-"7G"9-J"?.99"78I@89".(  1.5-"."/9 9(=(9@1%%".-"

bd Nc /! N .( "(8-(.(9"!@8"7:.9"7.(/-59'>@ 1.51/"/98J&#$$+%&#J

_]^cHdcI^`Q_^J!1(I^]J^]^cN+J.1-(..J_]^cJ]cJ]]a

_eJ ':7./ G +:/1=( G!"-89"(/ G(-,"81/G 1-"78J  ,1%%:/ 9(1/--9"7/9(="

1.5-"."/959'>@."-(179"8(8 '".(  :9"7"/-%(-:7"(/.( "J $$+%&#J_]]`H^d]U`VI^b^dQ

^b_`J!1(I^]Ja]afN+(..:/1-J^d]J`J^b^d

_fJ ':7./ G1@"7G +:/1=( G"9-J7"9."/9>(9'/(/'((917@.1/1 -1/-/9(1!@91

.1:8"% 9175719" 98.( "%71.(/!: 9(1/1%515918(8/!7"/-(8 '".(N7"5"7%:8(1/(/+:7@J $

&'(&#J_]]cH^dU`VId]dQd^bJ!1(I^]J^ce^NJ_]]b]d]cfe

`]J =//!"/ G &"7G'G78.:8G ":="/(/, G""-"/J1.5-"."/9

'"75":9( 8(/9'":-9(Q7&/1/17I1171/K9F(&%*$$+%&#J_]^fH^]I`_fJ

!1(I^]J``efN%(..:J_]^fJ]]`_f

`^J ':/G !!!(/G (: G"9-J 9(=9(1/1% 1.5-"."/9% 917 1/97(:9"891.:7(/"/!':./

.@1 7!(-(8 '".(N7"5"7%:8(1/(/+:7@J &%J_]^dH^_UcVI"]^dfab]J

!1(I^]J^`d^N+1:7/-J51/"J]^dfab]

`_J >"(&7! G98:.191 G.(9' G"9-J/'((9(1/1%9'"-9"7/9(=" 1.5-"."/959'>@57"8"7="8

5'1917" "59178%9"77"9(/-(/+:7@J (%)#J_]^bH__UdVI_fdJ!1(I^]J^^_cN8 (97/8-."!J^ae_

``J /!G':7./ G 7:8G"9-J-9"7/9(=" 1.5-"."/959'>@ 9(=9(1/(8"88"/9(-%17

(/%-..9(1//!+1(/9!"897: 9(1/(/9'"588(="97/8%"7.1!"-1% 1--&"/Q(/!: "!79'7(9(8J 

$$+%&#J_]^cH^ddU`VI^f]aQ^f^_J!1(I^]Ja]afN+(..:/1-J^ddJ`J^f]a

`aJ 9:!@1%%"9@/!%%(  @1% ]_`(/9("/98(9' (!/"@(8"8":8"!@/%-..9(1/J

'9958INN -(/( -97(-8J&1=N 9_N8'1>N]``d`ac^

`bJ

`cJ (8(9/1G7199J1>7! 1.5-"."/9(/'((9(1/_J]I"?9&"/"79(1//9( 1.5-"."/9&"/98

%17571?@8.-/1 9:7/-'".1&-1(/:7(J$  $*&#J_]^eHf`UaVIbcaQbddJ!1(I^]J^]]_N+'J_b]^c

559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager 559099-L-sub01-bw-Jager Processed on: 10-5-2021 Processed on: 10-5-2021 Processed on: 10-5-2021

Processed on: 10-5-2021 PDF page: 199PDF page: 199PDF page: 199PDF page: 199

 QYY



 

8

Download het nu "University of Groninge..."

Outline

GERELATEERDE DOCUMENTEN