• Keine Ergebnisse gefunden

Untersuchungen zur biologischen Funktion der „Processing“-α1,2-Mannosidase IA mittels „knock out“-Mäusen

N/A
N/A
Protected

Academic year: 2022

Aktie "Untersuchungen zur biologischen Funktion der „Processing“-α1,2-Mannosidase IA mittels „knock out“-Mäusen"

Copied!
96
0
0

Wird geladen.... (Jetzt Volltext ansehen)

Volltext

(1)

Untersuchungen zur biologischen Funktion der „Processing“-α1,2-Mannosidase IA

mittels „knock out“-Mäusen

Dissertation

zur

Erlangung des Doktorgrades (Dr. rer. nat.) der

Mathematisch-Naturwissenschaftlichen Fakultät der

Rheinischen-Friedrich-Wilhelms-Universität Bonn

vorgelegt von Michaela Hauptmann

aus Lingen/Ems

Bonn 2008

(2)

Angefertigt mit Genehmigung der Mathematisch-Naturwissenschaftlichen Fakultät der Rheinischen-Friedrich-Wilhelms-Universität Bonn

1. Referent: Prof. Dr. Bause 2. Referent: Prof. Dr. Koch

Tag der Mündlichen Prüfung: 09.06.2008

Diese Dissertation ist auf dem Hochschulschriftenserver der ULB Bonn http://hss.ulb.uni-bonn.de/diss_online elektronisch publiziert.

Erscheinungsjahr: 2008

(3)

!

! "#$#%$#&$#'#

!( )$*

+),#%-#. /

!0 1#%$#,# 2

!3 #4##)&$#$#54&6 7 !/ 8%&$#)+#%#.%9:9#)4&; 3

!< /

(! <

(! +=##.9#%&59>%9#6*)

+'*.% # <

(! ! )#*9#9 <

(! !( #')9#%4%=# 2

(! !0 #?'=%9%+'*.% # @ (!( )#*$#****#?'=%9% #

A #*###*# (7

(!0 9#%)9: (<

(!0! #*:9:*"#$B##*## (<

#*%

(!0!( #$#59CD%6

#*#$#59%D%69#%9: (<

(!3 -:#$'A9#+##. 0

(!3! 49#+##.)A9:

): 0(

(!3! ! 9##'##E,#

9# %)9: 00

(!3! !( E),#$9#%)F

= 03

(4)

(!3! !0 ,#$9#)F

)): 02

(!3!( ?'#9#&A#

F$'%9: 0@

(!3!0 9#%4): :*

&$#$'*)A 37

0! 4# 30

3! **) /7

/! ?'* /(

/! 9 /(

/! ! &: /(

/! !( * * /0

/! !0 9:** //

/! !3 ":** //

/! !/ //

/! !< G9 //

/! !<! G9)" //

/! !<!( #= /<

/! !<!0 G9)% /<

/! !<!0! 9% %%=** /<

/! !<!0!( '%'))G5 7?"6)#'## /<

/! !<!0!0 &G /2

/! !<!0!3 $'G /2

/! !<!0!/ (?)** /2

/!( 9# /2

/!(! 9###9# /@

/!(! ! )#*##*'" /2 /!(! !( ##-*%45-**D%*':'#6 /@

(5)

/!(! !0 -#$*%=# /@

/!(! !3 A#*###*#%9#%

)&#$'- />

/!(! !/ #*4%H />

/!(! !< 9%?'* <7

/!(! !2 ##4 <

/!(! !@ ##'# <

/!(! !> #4%1* <(

/!(! ! 7 ##4%1* <(

/!(! ! -:'##*4*$#**9 <(

/!(! ! ( -:'##*49%A' <0

/!(! ! 0 4%)# <0

/!(! ! 3 %#&A <0

/!(! ! / %- <0

/!(! ! < #%"#%$ <3

/!(! ! 2 #94%# <3

/!(! ! @ $##*%1#%"# </

/!(! ! > #9*##* <<

/!(!( *$9# <<

/!(!(! -#**#A$ <<

/!(!(!( 4%-** <<

/!(!(!0 #1# <2

/!(!(!3 ##*%1: <@

/!(!(!/ -#))9* <@

/!(!(!< -#%1: <@

/!(!(!2 **##$ <@

(6)

/!(!0 <>

/!(!0! =#9% % <>

/!(!0! ! *= <>

/!(!0! !( )##*###*# 27

/!(!0! !0 #)##*###*# 27 /!(!0! !3 =$#$'%$#*###*%# 2

/!(!3 ?'* 20

/!(!3! %#9: 2(

/!(!3!( A) #*#9%9: 2(

/!(!3!0 '###/2"D<'A 20

/!(!3!3 B##%"#$ 20

/!(!3!/ I')=*: 2/

/!(!3!< % '9%D%% 2/

/!(!3!2 ##9#)9: 2<

/!(!/ &A):#-)) 2<

<! -* 22

<!( @7

<!0 : @/

<!3 4 @<

(7)

!" "

# $%#&

'

#"( )*+,#- %./0/0/1

"2 #%%33

#" #3%%

#'4 *,#3%

#'( #3%

# #% 5 2 #%533

#,6, #3336,%33

# 273

#2 3%7 8 , ,,%78 4" 49

4 4

5

#8 %3%,:,333%7

,%7

3

82 8%3,,23%

82 8%3,

7 7

2 %, ,#,),2375%

5 5,;)<:= 5

>

(8)

5# 5,#

? ?,3'

?4 ?5,3 45

'

' '

'

'( :,'3

7

(# 3#3

(4 ?

:/ 33:/

%%,53

33

" %"3

5

5

37'

2

5

# %

" "

2 2,7,#2, 2 2,#2,

2 2,;8%%3%=,,'3

35

2 7

@6@ >>

A6@ A3>

7 ,3 377

B, C,,+,"3,:,%, ,#,%

>

(9)

! !"#$

" $ $%& '

' (% ") * +

+ &$!"% ,

' (- " -- .

'' /0'"- !1()2")

(34 5

'+ 6!7"4 8!9"- ':

'; "& /0'"

- " ''

', < 8!9"-"4

(1"# '+

'= " "$ "# ';

'. 9$ $!$"# 2 1

> ?;: ',

'@ 2*A2*> ;:B '.

'5 $! 1$ -*)2 '@

': $! 1$ C-"D"E-*)2 '5

' $<!1

-"D""0-FDF"G$!"- <

"# =+ +:

'' G $> - -"D""0

-FD""G$!"- + '+ H* 8 (*3> %>

1$ C-"D"E"G$!"-* +;

'; (1-"D""G$!"G +, ', *(1-"D""

G$!"-*9 +=

'= - !(> (

(1-"D""G$!"-* +@

4

(10)

'. $> <<

G$!"- +5

'@ "&( ;:

'5 I ")> "&(

-"D""0G$!"-)

2 " ;

& 2 ( $ $ C2 E

J

(11)

!

"#"$ %&

'()*&+ %%&&

%&,

-. %&/$0%%&& '1'"#

&&'

. %&/1$*

2.#+")&+'

3 -.% $ &

1 & + -. %%+ &&.

"!+40'/5657/+1%

.% % & )+ "

8/+9,

': #% ;!5 )<.+* =.%&&

&&)

<': > ?.+ =.." -"+

-%+@-#:+%&&

;': & ;!5 )<.+ +

$4A+A+/56B7

= =.. )<!5 ;.+ & 8+/

=..$% /+4'/5C5D8'/56<D1 )/ 5557' =/ %&% ="/

-8.!@)'':'=#%+

%#8.!E.)%..

&&"=. )+=.1"=.. )/

E ).8 " +*+ ! =..

)<!B " @ 9 =." $ = +:' = !/ ).

>F&&? % / &. 0& + # 8.! )+""

! =.. )<!5 ;.+"

(12)

40 #/ 56C7' ) #% =..0&

=..! '=.. %%"/"

=.&=. ' =.!'

!

"#

F=..

-%+@.&:+

& + )& %&& * 4A+

A+/56B7'/1+*.

%% / ) & &&G

"%&).H.#I/HJ)9 4!/5CKD10&/5C5D1/56;7'

=& ;!5 )<.+ >+?$

&)&

α/<. 8. @)' '<:' )9 α/;. 8. +40&

<

(13)

'/56KDG'/56L7'=!5 )<.#

>?.-8.! ' 1 !6 )<. & 4#&/ <MMK7' )& 8.

" =% / .α./<.

! % 4 #&/ 56C7' = %/

/ & & + ;.!5.C )<./ !6.L )<

;.!0%%&4!#&/55M7'

$ %"&'

;

(14)

= !+I8+ . > ?.- + & + % %%+4A+

A+/56B7'$" .α/<.!@α/<.

!).N: α/<. !1"!B <

"!6 )<.#&4! '/55KD/555D%

0"/ <MMM7'= 8+ !.)& "

#& + α/<.!/ . %& "

1$ '

= 8/ ;!5 )<.# !B )<

/8. / .α1/<.

.!/O>+*-.?

' !B )<.#

& $/ 3 8%% /

>&-.? '

#*+3 %&- E ).8+!B )</ ).+

% ' 8%

)<!B <.#"!#/9 P.;IP.L.!. +O 4/ 5CC7' = )!; )<. " %%+

@ ).+ ./ %./ #%./ F%+: +

%%'%&1&+*-">?/%

&%&)'';'=1%$/

;!5 )<.+ #&

$ '

K

(15)

$ (% ()*%+"

&,

"( P. %>+*-.

?" - * % +@

/.P/<.!/ .P/<.!: 40& '/ 56KD

#1565D!'/55KD0"/5557'

8. /)&&#.A 040&'/56KD1/565DA '/ 55B7/ %& .&/ .

&/@!=:9%=

/ 8.'= %& % C.5" ..).#G //)

"0'@<MM;: /8.+ /J+*

8. % '

B

-# "=

1 .-N.#@), )&D ),.)%D! ,! D , D , D

#')',#DF,F:4A+A+/56B7

(16)

. %&/

9P.@MC=:2.@BK=:' F% /2. %"/J +* F P. % " ' =*

2.N.0=.#G "/

.A&8 *4'/55LD0 1/55CD'/<MMM7'

.P./<.!/ 56C " #& / )&&# * %+

411/55L7'$=)+*

% 40 '/ <MMB7' 3 / .P./<.

!%&.!& %=@C)#:/

@5)#:%"/=

@K;K )#:' + )&& & +*/

#G " + % # !=

++* . %41/"O++7'

) )& P/<. ! " !5 )</

!B )< +*/ A 8. α/<.

! @8.! : " .& + α/<.

!@ .α/<.!).N:'3 O

" α/<.! %& &' ) )G '3 .α/<.

!"#G @BB.L;Q:+/

#G * 8.! .

! @;;.KQ:' = " .

!+N')++/

+*+ %+. '& +&

+ 4% '/ 5567' F 8. ' .

! *#& +'#&

8.! 9 ! 1 & + !6. / .!P.1

L

(17)

!5 )< 1 " !B )< %% 4= '/ 55KD 0"/ 555D % 0"/ <MMM7' 0 8+ !& %/

1/&')&& /

"@ '#:!5.

!@α/<.!):/" α/<.!1N/

" " α/<. 1 !5 )<.#

%%4#1/565D1'/55<D11/55B7'=

' & @": ! 8.

!" &/+*&#& + % &' = " 8. .!

0+/=% ;!5 )<.+.J . %&%& O .& +

# . .3 '

> ?. O' = + # "/ + 3 9 #&/

& - "/ O/

. %& & + ) +*

#++F "'- +/.

& +1" .

"+'

- . "

=& + F. $ "

"'1/-.#

&%+/ '1'O/A+.

%&/+4#&/55MD#/55;D/<MMM7'=

. % * & + /"( / 1%G " % $I- + '!/#. %&%

C

(18)

@#% =.. )<.+/ E + )& : +O%"

/ + .8 ++ &-+' '1'0+ 8.α/<.!/

!5 )< & + !6 )<. *+*/

-/ '1' F / .α.! & 4/ 55;D

! '/55K7'=* # +)

" α. % %%+/

$ " . % " >.?./ % & %& O 4A+ A+/ 56B7' ) " % " . 80+/ ;!5 )<. +/ )&/+*

/ 9 #&

" $/ + .8 O

% / ++ &

- '

* 1 +*/ . - / '1'$/$

$/'&/

9/ 8 '1' F/ #

#"/4/565D/55;D

"/55LD#3/556D=%/5567'

F@: +0+*/

;. =.. )<!5 ;.+ %& "

)&* 40+ '/567')"#&

@5C5: "/ ) >#? +*

E -"+ + %&& -#

' F* >#+? & "

) &%&'=

6

(19)

1 +/ " =.. )<!5 ; * %& @ '1' =.. )<: = -#.% . %% 411/55B7'

" 0 ' @55K: " ! & .

!5.C )<.$+#*F

". %&8'#. %&/.%

!5.C )<.A / " N N . 8 N& .+ . & + ' ) . %&I.A& & BC/ +.

/ F& ' )9 &. %&/

+ + "/ " 8 &

& ' F++ . %& "=. , %&. %%+@ : %NIN.

>F? +*4/<MMMD80/<MMM7' . %& =+ NIN.$%

+ "/ 8 * / ) #9 +* $ "' 1 8)=@( : )& &8.

! 8' # / )& P/<.

! " ) ;!5 )<.# 8.

! 1 !6 )<. @!61: +*' !61

& +/'=!@(8P..

&: / +3 + . %& +*

8 ) $% @& =:

+*43'/55LD0'/<MM7'0+8.!

P/<.!+N.)!5.# +3

# N/ # +* .& = 4#&/<MMK7'

)&

" =% 1 .P./<.!

4#&/56C7'= %/++>

5

(20)

&R. /&& + ;..!."

). ;.!5.6 )<.-4!#&/55M7'1 /.P./<.!)>#+R*/

/ " 8 % . %& '+/

.P./<.!%8/ . NIN.#%/F. %&

O4$/<MMM7'

=1&1+*/& +-/

>+* -.R / $ +*

"F '

/ 0 % 102

)+A& ;!5 )<.+ . %/+.8/

*/#O. %&++.

+)" 1% %.

")+ . '

56M"A (#O . %&++/+

)"& *+*4( '/56MD"

#+ '/ 55B7' 1 F %+ A =.!+@SMQ =.!.:/ & AG

@ '1' &% 8 3O: +*' = " " #O . %&++/ "

F/N= T@>0 -+

%%?/ +* >0% + %& #%?: ' ) " )9 J %+ " 1 N= . " ++/ * &

#%&@ '1'8/=%+/1

M

(21)

#%:/ 4F /<MM<7'

3 9 $ %/ %&% / N= T &&,N= U "%& + =+"

%/ )+=.. ;!5 )<.- E + ' ) N= T %& %+

/ 9 . - ++4A '/555D!GF /<MMD#/<MM7')

" )9 J %+

E " $ @0%&%%: / - #+'=++ . %%

+*+ ! ++ . %& " +"

F I #=#./ 8% + N=

4= '/ <MMM7' " ( $ . %%O + +'=N= .%&/"<+

I+ )" " % =..$% @%& .: +

#O -. @%& .+:/ ' +'3 /&AG J %+/ +*/=

N= .9'

0#

()

&

%

"3435 6

)

&

7

12 %

&

@!!:

&

@!:

=..

,!5

)N<..

=α/;.

% +

!!<

!

) L

<<MLB LMC6B

LM<BC5 BKBBM

LM;KC LMKBLL

L&;';.

&;'<

BG<<.G

&<<';

S;MM

S<M

S;M

%.

8 +/

3.

N.

&/

%.

8

#+

'/55B

=A '/ 556D ( '/

556D /556 '/

555D 1 '/556

(22)

+

J

=..

!,!B

)<..

=α/;.

% +

=..!.

#%

=..!.

=+

=..

!,!C

)<..

=α/L.

% +

=..

, !

5 )<.

=P/;.

% + =.

!,!

)<.

=P/;.

% +

=..

).

&&

+ =.

!, )

<..

=2/K.

%.

+

=..

!,!@L:

@6: )<.

.=P.

%.

+

=.

),α.L.

=.

!β./

<..

)%

%+

@ :

α./<.

) ;

=!

!=

) <

) 6

) <

) C

)

) 5

! )<

N#

.

LMM LM6CBM

LM;BM;

LM6C55

LMKMK LM56M

LMCKK LMCK;

LM6M;

LM6MK

LMC5MB LMC5ML

5;BM LM6M5;

LMB5MC LM6BKM

LML5K LM6CCL

LM;B6B

<<MLC

<<MLL LM<LL

LM;;L

<LL<LB

;G<C

<MG;';

C&;'.&<

<<

&.&B'B

5G<<

G<;';

L&;';

G<;

KG<

<&<.;

&'<

<

K

K

B

B

<

<

L

K

!.

&/

0%&

O

!%

1

N.

&/0%&.

&.

&

! 8/

. O

! 8/

!.

&

0&.

&.

/0%&

.

&/

" O

!%

%.

8/

. +

A ) '1/

A'/

555

'/

<MMMDA '/<MMM

#'/

<MMD A '/<MM N /<MM<

N '/ <MM;D

# '/ <MMKD '/

<MMB '/

<MM;

3 '/

<MM;

A '/

<MMKD

# '/<MMK

F '/

<MMKD 3 '/<MMB

( '/

55K

= /<MMM

* '/

(23)

+

=.F.

&

@$%→

:

=.

,.

)%

. β/K

%+

"

&

N!.

&

1K )

N- C

.

LMBL;K

5

;

<

" O 0%.

&/

!%&

&&

&

"

1

<MMD * '/<MM

0 '/ <MM<D '/

<MM<

3 '/

<MMK

! '/<MMB

#0 % 1024+ 1%0/<MM;7 V-!!,-!!@&'II''''"I:'

)&& $ 8' " N . %%O@N= :+/+=+

4='/<MMMDO'/<MM<7'%&!

N= . " )+ .P/<. .P/;. .P/;.!.

'=&. %+* ! . WN.) " ) WN.

)*)/ &).#

" .+*'=+)" %@X ;Q:

&AG +* +*

3 !' =

! )8"%&!+' )++A*F A&+/ *&& F #' = " "

3 ' $ A&+

=%+ %")

#&+'=1& / +* +- F %/ -.G /

"'

;

(24)

8 9%) * ,3'3%+0:

#O . %&++ +* !/ /

!% @N= T:/ #%& )

"J %+ O @ ' ':' = = A/ )+

/ 8 ' & + + )%"+/

+*'"#O

". %&++ O/

( > ?.! +* N= T / % 1%G & + ' F* N= T

" %& @-.: ! / +* @!<. : +* .P/<.

!1' =)!<. @N= :+*

%& "EN= .'

# !<.+ !/ N= '1'

" O3/"&%)"/#&

4(/ '/55KD3 '/<MM7'=F .!1.)"

+* ! & # 4%/<MMC7'&N= .%&/ %+/

!'J 9//

F/ +* & # / P/<.! 1.=+ "

O'=1&/0">.?.

!") /+11%"

. %& P. % %%+

'

K

(25)

; ! )

= )&& " 1 + ( N F% %>+*-.?/

.P/<.! ) @!5.!: O' = P/<.! ) / .P/<.!1N/=%"

>.?. !B )< ' - " .P/<.

!-.& +8 A /""')

")>?.!/P/<.!

). & + ' )9 / F ! ). + + . & + !'

B

(26)

! "

!

"#"$ % &'()

")#!*" ( # +,-). ( # /0 &'() ") , 1! 2 34,,% /(##%)"

!

#"$%&" ""

5%6+,-).7 0(

# # ( ! / " # # 0"(6 . %!7 0" 82) ") 7#!*, 9, % 0(#

0:*$!';<==>82)?7,@

!.## (.") 0(

% " ( # :==A> ?

"70 # :B;A>! , @ # 0)@C " 4, :D!!'!D>!

1 +@#- %# 4 28)

?7#!. 0#

7 0"))@EF4 5"49 C 6 2, , ,(;;DGH :*!''<BI>!#71 0, 0%!

82)" "),

'J

(27)

0 %"!!'!

. &'()):"!!'">

:"!!'>$82)" K

")'I27#2 :2''I>!2')71 ) 0(2';;,) 0 DL MN 0 % ) 7(

7(47#MI=,7

!H147#2M)'I(#

,)C';;,#72'I!

"$ '%"()

* %6+,-).(#

))")5/@$ ") ( %)#!C) 0:D!!'!'MKD!!'!'<>!

")''+-)5( C)6 H1M=, H0 #(#@8 ,7C)6,!

$ 5 , # C)6 ( # ) C)

!) 7C)6 5C) !,6 5#"$HC)

'<

*

'MIDJ<=B';''''M'I

'MIDJ<=B';'''

##+%"#%*

(28)

65/@. %!"6

#, :D!'!J!'>("

:D!!'!> 0 :D!!'!D>! /# C)6( ) 6( C) (# 0 ,!E#6 ,7 0 ) #! C) :)4O

@C''5<JJPKC)4O@C'''''M=P'>!

, "$%- & ! "

*") : )/>

+,-). ( # . ( ,7 $) ") " , ") 0 ( ) :)2> C) :C)2> ! 0)2Q7'=I<,(<=DN#7 )"4N2! % 0' 2''D<D #72'!C) 2 0 M<I< ,( ';J=

#7 ,)C2'I<'<

2'I:"!!I">!")5:)C)2>#

,C)6":!!>4,@C, :D!!'!M>! @C)@ # DL)#7 #! ML)#7 2, 6).

( $@4 :$,2)@,)4 >) 6$@4)@, :@6>)@F!('BBG:"!!M!I>!

'=

(29)

,' M

M

##+$$"./ '%010"

2"! " " ")5#

@C, :D!!'!M>",

C)64,! ,'O'")K ,OC)

@C)@:M<I<,>K ,MO)@C)@:'=MI,>

" ! , ) #! C)2 , @C)@

," !3 ,(C)2,

@C)@#H1 7I(#7)2, @C)

@H1# #: ,M>!5#

:D!!'!B> :D!!'!<> #!

:, #%#@ %>

2, 6). ! 2, 6)")+,-) ."!M!)C) 2 # 0 %,% ! . # 1 % 4 )/!

'B

(30)

##,+&%%&" " ! "%- & %@C)@

"!! %)4:)2> %C)4:C)2>

3" #"4"&'%- &! "

)%5"%$ #6&7

)/ % ( ,#H,/(

4,F('B='K6 ('B='G!$

.( )/ # , / 0($@4)0 (7 ,, ? :+C -> 0 / , 0 :"!!I>! "

+C-('O';J 'O';<(#

)/ $ . , :!!$"4) (I'=

>! 5%4 2, 6)").# )/

4, 'B@89$ $') )/ #( # @ ! : %

@ C( *7 > . % #!

,.:D!!M!'!<>#

;

!

*

%- &

8,9#

,:9:#

(31)

)/ 5)"%"#$@4) : > $"4 :,2( ,( 3>) :D!!M!'!M>! )/(

$@4) $"4)#(1 ! )/( $"4) 6 %( # # '; 4

! M=I ) $"4) #!

#1H16#(

/ % C

@C ):D!!'!IKD!!'!'M>!

'

(32)

/ 7 C M=I )/ # / " :!!> # 3,)" #! # ")" 4, @C :D!!'!I>!/", 3,)"#@#(

./

"

! "

%- &

6 6 69

3 &

R

C'D SC';

R SC';

. $

03$

)*-/8 # 1*-,/: #

0 0""

#./

"

&

#

@C)

@

@C)

@

##9+3"$$& "$$ #./

"C#@C)@:C'D!C'; %34)"K!

C'; %">!( % 6+,-).##:8!.8$>!C Q ( % )$##!

*

1

&

(33)

01C)2(#@")@ :C'D>D N#7 C)2 2 'I 0 )@ :C';> ) 2'I:"!!I">!@

I(' @C)@ , #! / #

")"# )@:C';>#

")@ :>( 0 ,7 # :"!!I C>! 5 M(< 1 @C)5

#!

M=I )/.

")":6!'J(D(JM(''I(;MMJJ>#

#!, %,6"

!D3(#6#I('1@C)

@(#3,)"(")"(

#M(<1@C)@ (#!

M

9 #

)6!

#;" <=3 ,<<=3

< ,<<

>=3 ()

9=3 ()=3

> 9

##>+)%5"%$

#%- & ! "

"'"6& 7,,@C)

"#7 )/

:!'J(D(''I(MJJ>! , E#@C)@(#

", @ %3,)

"! ,

@C)@ (@

% ")"

, #!"#

@C)"7")/#!

(34)

/#"@C)#"@C) , )/ ))" %:D!!'!'M>!$#

7" ,!" @ ) 3,)#!",5 3,)"I(=15")"

I('1 ,, %:"!!I"C>! ,,#

1$ #J;;, #(

ML ) ,,! ) )"("!J(( ) ,

" % )/5#H1

#:I(=I('>!

/7 "7(#

@C ) )/

6, # :D!!M!'!I> FQ !( 'BB<G!

6, # @C( ))"

,C 4 1!

I

> # 9 #

=3

< > <, 9 ?,

)6!

##<+& %"*4"%$

" #"6& 7 )/

"# ). ) ! % / ,")5 %34)":I(=

>" % ":I('>

##!

(35)

3(" )/C TI;6#MA<MA!/

C"!<!

, )/( 6''I/

" : H3>!#

)/ H @ C , :6JM(D('J(;M>!4+-+-

!6''I"#%

C " ! . /# )/DJM %E#7(

D

!"#$% &"'$% !"($% !"#$%

#) ** ** + ,!"--.

/, ** ** + )-"--.

)& ** ** '&"--.

##! ** ** &/"--.

/-& ** ** + ,#"--.

&)) **

1%" ""$@%$" #"6& 7 "

##:+"44 46& 7 1%"'@A9? )/#

/ , ( 9E7 , C 57!!

(36)

6H"/C1 , 7#!

, 6"'$$'"B

, 6"'$$@%B"B*'4C %$

" #""6&7

$ , )/4)"#!

)E:D!!I!I>77(7

#H!#7/DJM#

E( # CD<8QJ)3 #(

1",!"#",,

@ !3: %*7> %!, (6JME#(4'4#

7 7 : 7 3>( # C7!I;)J;A #!56D#

3 2, 7 ( 1#U!

, 7% 1%" ""$ %"'4$" DE %'4$"

EB

7:73>#

CD<Q8J)7,!., ( 6(:"V8)>

) 5 ! 5 'B@89)7(,%$') )/#!"

74# (E74:"!!=

C7 W'> 6 D;A

! " ., C7 W' CD<Q8J)3 M=U:5')>('=) 5

J

(37)

1 , #! % .,CD<Q8J)477:C7 X'(C7WWM>1#!

, :D!!'!IK D!!'!'M> #

%CD<Q8J)4,(CD<Q8J) ,!E#, .,45):MI7>

# 1 @C ! " 4, % @C # "

( #,4#!/#3,)

#! " # @ #( # 6,!!:@C';8C'D#!C';8>!* , 1( # E# @C)" 4, %!"+@-"4,(

)/ JM#!@C)" 3,)(

# 7 )/ JM "! !B 2,

! ,')D@C)@(3,)",

@#( ,<)''@(,

@ %"!3( @C5 3,)"I('1@C)@: ,>(EM(=1

<

##8+1%B"F1%B"$"@9?G C7.,CD<Q8J3 ) ")"#$7 #!

(38)

@ % " : , =>!

:"V8)>4# )/JM(###I('@C)@

: ,M(ID>YM(=1@C)@: ,B(';''>(#

. " ! . MI 7

#'<45):';3(<7>!

( ")"#D;A

##!

45)#1(

:")8)>77+-")

!".,':5M)>(

@C ) , #! " !';

#7 @C)" ( #

"#"!!B3, , @C)@ # : ,')J> 7 @C)@ %

": ,=)'M>!#71(#53,)1I('

= 9 #

& ",9><:8? =3 DE DE D =3 DE DE D

=30"" 0""

##+4 "$%"'4$"B01

" #,"#4, %

@C#")51 , ! ,'!<O:

">K ,!=O3,:V8V>K ,M!BO =IIM:V8)>K ,I!';O =IIJ:V8)>K ,D!''O )/JM:V8)>K 34)@:C';8C'D>K@ % ")

":C';8>

(39)

1 @ # : , M>( 5 :")8)> 7 1M(=@C)@!: ,''M>!5 )/JM##M(=@I('1@

: ,BKI''>!'''7 7+-"):")8)>!

/"@C##"")8))4 ))" %! $#" #, (1 , ,, ) !! #! " !'' 2, ))" % E# :)8)> # 6 %E# 3, :V8V>)( :V8)> % ) /JM!3 Q ) 3,)#!

"#( "3,):V8V>1 YI(=: ,'>5:)8)>1 %

B 9 #

& ",9><:8?, D =3 DE E E D =3 DE E E

=30"" 0""

##?+4 "$%'4$"EB01"

#,"#4, %@C#

")51, ! ,'!=O :">K ,!BO )/JM:V8)>K ,M!';O3,K ,I!''O B;M :V8)>K ,D!'O =III:)8)>K ,J!'MO =IID:)8)>K34)@:C';8C'D>K

@ % ")":C';8>

(40)

",I15: ,T=III>!

# 5 "# " 5 :V8)> )/JM#: ,MT=IIMK , I>!

%@C) ))"(

")8))7 ") 7 #! "

,4)@C("V8V("V8)")8)) 7#" %#:D!!'!'D>!375"V8

V "V8))4 .# @

")#'1@C)@, #(

# 5 5 ")8)) # : >!

? " + - # )":D!!'!'BKD!!!<>(Q4 %#:"!'>!375")8))2,

"##: ,I>(#JB"@#

3,) : , > : , J> ")

")"H, 7!"))"H,

M;

9 #

> #

& " , 9

##+& %"*4()

& %5 '"E/DED

"=4 5"()6&

7 <,"# ,

!!

#! ,'O3,:V8V>K ,O =III:)8)>K ,MO =IIM:V8)>K ,IO ) /JM:V8)>!

=3 E DE D

(41)

,7,B1: ,'(MD>(

,( # H 2, 5 ,7,#!

9 0%B4 %5" $

3:"V8)>:")8)>7E @7,! # 4.3,)7"#%

6H,( 9#( . Q# ! "

., 3 :")8)>

:")8)> 7 : 7 ,

#4>!, %("

") 7* %!

M'

& ",9><

< ( (

##+="#4@ ""

E/DE"=4 U#'Z

, #, ! "#$

"H,#:)"6#! ")"6>! , '!O3,:V8V>K ,M!IO:)8)> K ,D!JO :V8)>

=3 =3 E E DE DE

(42)

9 (" 2%"#5#%B'""B

*%,% (") #")8))8 7 ")8))4 7 %( # 7 7:")8)>3,)3:"V8V>#!

:"V8)> 3 ! 7 57 ., " :"V8)> #! :")8)>

! ( 5 "

5, 7 7 ")8))7 #! 3 3 :")8)> 3,) :"V8V> #!

:"V8)>7,(#5U!(

" 7:")8)>3 !

*$# %* 7")8))3(#

7 . 3 / :V8V>3!/#%I D4#@@(9(!

/#9

!@/H.

/, . #! @ @ ,7, (#79,.

! !", Q#(#7@.

Q,!41

@/./, .(#5*#

3,):")8)>3#!, %( 7 ")8))3 H .!

!

M

(43)

9 " % %$% H"%$ " I@" @ 'B

H* % 7") 3 H 7 5 % ! 5 #7 9 # 4 ,7

@7 !E9#@7 7 ( # # 47 : )5> ! 7 ( 47 ( ! 5!49H147 ! 9 5, :>

:H,>(#[$

:@>!

/7 # E# # 3,)3 :")8)> 3 9 , !

$ 1 , * # 9 ") 3 3,)3 *

#H: 6H,#E#

4> ! 5% C 5 H#9:")8)>3,) 3@ (*<Z% (

$728 7 :D!!D> *% '; #! I;

.H1 Q, ! " !'M

*%(")8))9:"C>

3, : > #! # @7, , :H,> :" > 5

#:C>#!5 5!

, %( " + - 5 #( H 5#* % 7" 3

##!

MM

(44)

9 H#"%I'4 ' =#% "

"#$$#

( 5 "

:")8)>3#*" .

* %!*$#

("+-9#9 ( # , :")8)>

3# 3,)3I) :D!!I!<>! \ , # /, Q, ! "

, 7 # ( / 71 5 #! 9 71 ( . ! ,7

@H,!/,/,

MI

E *=3

1E

(=3 1"

3"B"

& B"

1"

3"B"

##,+B-6$B"#H"2%@I@"

%'4$"E=4 B"O ")8)(';

.H1KCO ")8)(I; .H1KO34(';

.H1KO34(I; .H1

(45)

: , # 9K . @H, >( # +- !

" !'I 2, :")8)>

3:">3,)3:C>:"

C>#!I6:>!//, , " 7 " :" C>!

#71 ( .,7

@H, ! . 1 ( , , :"( #1 @ >( # 7 #7 % % ! I%

6 ) * , 9:")8)>3,)3!379(

4 #( /, # "

#:>(#/7" 3 71#!+% -!.@H,

#:(#1@ >!

MD

*

##9+H#"%6'E=4 =#%';

.H1"O ")8)) 7 9I6:>KCO34)3 I6:>!#1@ (

#!

1

(

0"B"

0 J" "%

"

!

3$

E =3

3$

(46)

I6:")8)>3

\9 #(!!+-#(#

#2,"+-.+- 5/6!,

"!'J!3/("

, " 7 #")8))3 3,)3#M)IDA!"H #(3,)3

##M;AI!,

"+-(" 3 / HI6 ';;A:

"!!'I>!(9 :")8)> 3 5 ") ( (#7!

MJ

0"'"K#$"#"K6'

@"$#"%"6'L%M

## >+ & #B #"%" 6' E =4 B "

"#$$* # 7 ( 6

/, ,!"+-##(

.7 #!

(47)

9, I'4'=#%%#"%$B%$

!I!'!*(

5" 79#!

")8)) , 7 ( #(

# ! , 2, # # %O

$ :")8)> 3 3,)3 # , 7,!3#4.,H : 9 ,> ! "1

# ) :D!!I!<> I %,% ( 9)/: %(

>! 2, " !'J (#""(C4

" I6!3"!'J(

3,)3(##()/(#

( ##!

:")8)>4 32, 5)/##:>(# , ( # I; .H1 :C> ! . # ")8)) I% 6 , ( # 6 :")8)>3#:>!, %(

" 3(" , #:>!

M<

(48)

#%(. %.(

" 3 ( 3,) :"V8V>( :"V8)> :")8)> 7 ,

#( #:D!!I!I>!

9 6- ""@"%5#@=4 B

( " ") # 7 9 ") 3 ! , (:")8)>7 :")8)>3 #!6"#

") # ,59

" 3#!7!1(

", "

M=

1E3$

N=33$

(

##<+ " %%@#"%#"%6'E

=4 B# 79 , 6% %!" % #4/#

I! 3,)4:"!T/#>

")8)) 7:(C!T/#>'; .H1#!I;

.H1:C>Q,!"(C4!"

#I !

& "

=3 E E9?%

3$

3$

* 1

6

(49)

), # , 2,#!*%,% #))

"" %(H4#

")@7,Q(((Q4 :D!!'!'J>! ) " !'< " !

"!'<, "@$:T';;A>!

3(#")@7Q(

H:J;A#!D;A Q> 2,( #7 2, ';A : Q>

!\2,9#

MB

0(

, #

)" ;#" %" ' ;$ 6"J

##:+)"%"*4@"%"5#

"5#%=4

!

"+@ ,#;Z )"

"#!"@$!O P"# ")2,(

"@$

O@)"%"*4"

!"

*

(50)

4!:;;<>!("#

9(#(2,#(

5(#")8))7(,7, E+- #57#!#%(

" " , 9 ), H (

",7#57

9, 6 ('' B % % "% !"B"$

4 4"$ "&""""%5

( @)9 (H ), %! , .7 # $ C) ., 7 Q 5:5>#! )@"#!#7 # 7 9 ,2 4,(

7:"!!'=>!

5 ) /#

(Q

I;

9, <

<:

) 1II

##8+& %%("$%& "3"""

)4 ",I'MJ''E#7) ,24,%, 7 7 F !('B=MG!

(51)

\Q 4 5!U C)4,( ) ,77) ! ",, C 4, : ) > # )

@5)" #F@!(;;;K.H(;;G!

# C 4, )@ 7 Q 4 5 )@"!

5 4, )@ 4 #:"! !'B(

,>(#74 ,3,) #!

" ##7 : ,' #! M>! )@" 7

! 37 "H, C ) 7 7(#3,)#!")8))

!

I'

##+ "%N "$

& (& 0$@& "3"""

"E/"=4 01(

#, E# 7#!@

,(,

# )4 ") 4 )"6#! ,'O 34) K ,OC)) K , MO ")8))

,

'M ,$=

,$D 6N

&(&06

(52)

( / 4

" 74 5"")8))7,#!

("($. C) #( H &'()

") !

I

(53)

!"# $

!"##%##&""' !"#$&" !"#(

)%* +" # !"# # ,"# -#./ .#".

# # 0" # &"!"# 1' 2 +/1*"/#+#!"#3 +#

!" 0" !4& ( -# /1 !5", + # # #

&" !"# , # 0 ,"# -# !4& ( .#".67""'* 889:,+.#7"0 88897"044492

*44;9*44<=*(+//+##

,0"+ !"#(#&##

0"#(++0"##0 ,"#-#,!4& ( +.#".6-+#-44>9-*44 9##-454=*

# # , +* +/ $0% +#

!" # # !"# +/ 1? '",/, /1#+#.,/*@,# -##+#

&" !"#-#) 0+/1 ,#!"#(1*

"-"(.#7.+####"1",#

&" !"#$()%,A10#'##, 1'#++*"/1/"16:,+.

* 88B9:,+.*445=*/1/.""C'"##&"

!"#+D'"0#*

,#-##&" !"#(1?#@+*#,1'

# # (+ E'"' "F! + + # # ., /1

#3###('#&#1'1#D"./

'* -##/,,,#

"'"+#0":,+.$ 88B%(+/+##7##

/""C"&" !"#-E'"'"GF#!++

#* ( # !"# -& 1? + # #

&+ , 1? :"# # ","." #1 H* ( 1? # "

+' # , '" C' # I+

#"##:/",+*?+#'

"/""(11'#1*

C?#7# !"#( ,##0"#(+#

<

(54)

' ( ( & 0# $ *% # 1"#

+#J

*% 7#E/,FA'""/!($(++* *%

*% :1'"0"@,#,"/!(A'"$ * %

*% # ","" '",+" 1 # '" @

$ * * %

<*% K'"@'"!-".$ **%

>*% '"#H1),,$ **%

;*% A/ # , ! , )>B-IL;! "."

$!(ML% '",,$ ** %

B*% , # + "." $!(ML% : #

","."#1$!(L%!$ ** %

2,/,:##"."$!(ML%"","."

$!(L%:,K0"#,##,,+'+D"./1*

(:,A2#./!'(+

N/+ ' A # I+ $ *<%* , C #

"." $!(ML% : 3N # # &"./ "

1'"1!"#((+*11#?+#(/, .,,#,#",'##+*#, # /"" C" 0#* C D"./,C#","."#1!"#(!?+#

##+++E'"'"F!,"###"#D"

+11$! &#&"!"#-&%#,/"./(11' +"+#$*"*%6:,+. 88B92* 889H'*44<=*

2 , # !(L! # # # #

!"# (&#1' " /"./ '* " # +"+ # "

,1 A/0 # /"0" # !(L2+ A/

#2+#,!(L",#! '",,0"*

7#1##C#!"#(('01#

C#","."#12+'*2#!(L!,

#2+0/,##("."$!(

ML% '",, $ *<*%* # "11 # ","." #1

!"#(2+0"#1+"11##!(L!",

<<

(55)

1"/11#*

, 7 1? # # + C" # !"# (

&#1' # 0# # , + C"/1.' $*-* A.' "0 C"'1%* A # # D#A.'!(L##2+3',"/""

(11' +* # '* ( # ,'"'"/ (. # C"'" ","." #1 !"# (2+ ""

0// ' # +? # C"'1 , A 2#./

2++$ *<**9(++* *<%*-"+#,##1

####!"#(&#1'0+10, 1 N D # A.' "# 1 N # "0 C"'"+*

(3# , /""00 # # #

","."$!(L%2+"".+##+

#2#./2+,,*2##'#+#

&"./,+#,#">#

# ( + ". ","." $!(L% 2+

0#'A#'+$ *<** 9(++* *>#

*;%*##C#!"#("111#+#

".' '* , ?+/?1 "+ # # C'" +*

-11'#!(L+1###".,+

#,$#,@/'"',"/""A#'+%

,/,#!,,+*

A" # -1 + , #, "' /,, # # 3

!# $@D%+#*(,"/1#/,,

# ., 1 # # @D , - # -? 1N " # # /,, # @D # # "# ## ' , 3# , #

@,,+#1"*,A1'",,#:

# +1 # @ +* !#,* " @ # 1"-1+#+".

2#./2+,/,#!,,+#*2#

<>

(56)

" +# !"# (#1

#2#./".#"'#/,# #

!(L####$,#%*#/,K#"

+ ".,,+ $",,% 0"# # , # 0,*

#"+#/,+#@DE'++F*@#,+

#!(L0A##".+*@D

''+(+0"/,+"+"#$ *<**9 (++* *B%* -"+ # 7 #1 # # 1#

-11'#!(L##,#+1O

"11 0" 1'"1 * ?# #, +###!"#(,+"#,+#(+##'"' '+,*

-# #,!#".,+

## 1?# "C" #1?,+."62, #

!"" 44=* + ,2 # &.'"/" $@D% # # +#@''6:+"* 889-"K 889(0 8889"

888=*-".#@DD"$##,#'%#

,,+0' A"1 . # + , #, (1+ # D".//#',+#+"",* :"'"##D/#'

#I,## ,P+/#/"(Q:

('/" # : .'".* +# @D,# # ?+ # ) :,,#!,+0'####!"#1'"-0"

"' ., $&"# # !"#% /" "+

+#"#0",E,"F:./6,*459&0

* 45 =* :/" # &" # # E ,"F,# # 0# !"#$!"#()#1/1@1

# !"# % /" # # .'" $ - 0"

0# &.'".1 # , # &" "' #%

&.'',,0",'",/:./,+*

# ",, # # , # +#

"#' , :/" 0" @D + # , C 0" @D /,+#'"6!'* 889H"0* 88 =*?+

<;

(57)

1" 0# - # &" # . # .'"# +#

@''* " ,,++# @D&.'"/" # 3#

D,,,+#/""@D #@DC,/".,

#@D?+#1#+?'P0#62,4559&0#2, 45>=* @D&.'"/"/ # # /"". 0" # !,+

+/ "# # , '"#", 1 # # #

!+#'#"###"*/0,

".,,+# 6R * 88 9@" * 88 9' * 44;=* C'"0 # $# # # # 1 # +!"#(#1!%'N#,'####C

#!"#(#-".P +#"#'1#@D

&.'"/" , 1? &" +" # # 1"# 1'"

"#,#+##'N*

!710"!,"#+##&1?#K@DD"

##@DD"+,,C'"##"#C"

"#*+#","."#1@D2+1#"+"' R00"@D #@D1"6'444=*,?+#E'"'"F 2+ 1? # @D # # @DD" 1* C # @DD" # ' +# 6' 889 I * 44;9 ' * 44;9 :" * 44>=*

7"."@D2+#1+ ,#?*?+

+7#@D #@D#/,'#+#+#*

@D # E1 /, /"F + # # ('"",'" , /,,*-#('"",'"#,("."##

#-##/,'"/1+,, +#"#',@D D" N # 6:+" * 88=* # ('"",'" # # '"",!,+/"#+##@D D"$E"#/,/"F%*K ' # /,, # ## # # /0 / # D,,,+ " 3 C" , # '",,62, 88>=*,#-"+##@D D" # '/" # +# ## " + # -1/*

2#+##(+#1?##!L

<B

(58)

0" ,+K#"#@D!'+#

"11C'"1'+$#**#/,'N#@D

#%*+###A#!"#(('0#-#

#@D!'",/0##+##11#-".#@DD"

# C'"1' + !3 +1 #* + # # ( #

!"# (& +,, E ,"F,#' # E1'"F 'P#+##'N"#"+##C#

!"#(#**#11#"#D"PEF1 1'"1@DD"0##'1-#0"#

# #* @,,1# # 0"# + K#" # # ( # !"# (& , D"./ 1? + #, 3 # C'"1'# ##,#C#+!"#(

#1!+"11*,&#/""C"

!"# - E'"' "GF # # 6:,+. * 88B=*

?+###!"#(#-$#!"#)%,#

-#+/11*'+##

##"1",#&" !"#1?#"#D"+,,

&.'"/"/0"#$*-*!"#(S &.'"/"

!"# -S &.'"/" # I% # # # C +* # /1 C'"# !"#".,,#,C+,, &.'"/"

##+## !"#'",/#'*

! # !"# (#1 ! # # 0"# (+

!,"# + + #, &#1' ., 0" , E1?F

"#D" + * # I # + !,"#

++ + # ., # +# "#D" /1

$! &9!"#-&%*E'"'"F#! &#

!1?++,D"./#0T+,,,+,

!++)&''1$)&%62* 889H'*

44<=*,C#!"#-!,"##+'D+++#,

# &#1' ,"' 1? /# )&'' 1

#'*(#/":,+.*$ 88B%#,#

<5

(59)

C1?"I/"+,#+#"##

!"#-1'0"#'N*'N#+#

###(+##!"#(!,"#+1

# ! ?++ #* 3 # #"' + C ,#

1#!"#(&#1'0#'#

*+#0"#70"E'"'"F!

+#.,# &.'"/"+".#

1"0/#2##+""C'".,#

&.'"/""11 # 1 #, 2 1"," #

?+/#,)&''*

<4

(60)

!"#"

$%&'()*+ ,-./01$

/ " 2345 # .& 6 2341$

//" ,, 1$,$ 2 !"# 1" 17 184 !"#$ 7 56 #1$ 7 + 9 #0

: ; 7 + !"# + *- +0$.&-"$/-;$

!"# 1 &-;" + / %-- ( " / !"# 1 .& 0

<-&-&-.&

*,0

'= !"#1 $$-/

-+0:&'>&-+%.$(

?-2.14--9@/0AB-//0#

-/ < .& : $ 2 8740 :

&-&$-$/,"

-7,C<$$$.0

$;;-,2DE4

$,&2E4/0

:,$,&$C+$

$$/-/*;,.0 .$ "

E; $ &.&&;" / / 1&

;&0$&&-1:&;"

; + / ?,- + -

; /0 =/ - - $. &&;- /0 1E F/ & 0 $ .++"$,21E4F/""

1EGA9//"

F,.F/0F.++),/

$.$;$$/"/

F,.F///-"/1EG/0

".$1E-"/&&/

9H

(61)

-0 : 2*4 &' )"

&' $/, $/ ; ),0 : / . &'" && $ 7 /$$

,-.- ? ,$-+; -- $&

-I"&--$"00 7

$1&0:'/"*/$

- ,-. 2*!A4"C.&- / '/$ )/--0:

1&- .& & / .--/0& ,-.0:"

,$"/1718".-).$"

/ + 7, $ + / /F,.0)&&.&-&' !"#17"/2J//4 <)*/$$ ,-.$

.>-/&&0:'/"C !"#&'--)*/$$ ,-.

+ ? ,$-+; 1&$ !"#

/,$-$.-0

1$ // /" ? 1 -+;*+"/&&

7,K / )- & *,-. $

&'214-&;-*

/</&/0"-+&-&;

/-0)/1/$$1$-"

%&-(-K"/-I"/

&& )*K" %( &

&-&; ** + " - & 7 + : 0

9!

(62)

!"#

$%&'

(')* +,$ !(,

(%&' ((-./0 !"

. /!1''

%&%& 2+ !"', '3%%&' /45 !)

1%&' *.56/!7 !!+%'%

1'89

*)) ))1 !(

*++*%,) '*':/ !(,

")' ;&*")'<+= !('(%&

"$,')' "$,"(*- !%&' '$

))/>?*&@ ,A5- !&!

B /. ', (%&')') ! 7

)'8& "$% !B$%&'

%% (% !(,

3'&, !1

'13$'' * !+

''$' / !+

'*+%&'*'

' ?- !%

"* "*C55 !B'%

& +%&0% !&%D

!E'E&! !'D

(& !',

' - ? - ? - !1'

+%&8'$ B.? !'1 +%&83$, +2*?/ !F$

?

(63)

+G'E (+A-1'%' !, (

+'''))@ 3%A !(,

+,% +/-- +'''

+$' $)%& +%&&3$' ' "( ?.

! !"

0%&$, (','+B- +> >

0%&$ (''+' /(- !1H"'''D +'4+B- !(','%'%

0*4 !F'IB'1

0*'' ?--% !&%B(

,1

'' 1%? !(,

4 !? !F'IB'1

2)' +(-+ !+'%

7')' B8&E'))1BF+*H? ! (%''DB8&E')/?*(1+*A ! +D$E')A*-? !+)D()

%',%&E')()% !"

,(9(+'/%+G'%'),%'B

(9'

(%''90%*7')'J&%&' (%&9(+

(E)'1$"91+E'-K ?K -K',-K (,9DL'%,:(%,M-N9-ODAL

'%,:(%,MAC 9-O /$%&93 )''+

/'%&9,')1'%/B

%9(%*' "4

'*B,9J')'*>

',9')@P D- ',?D0*B8'

!%'(%'97)@P8+*7 73

A

(64)

!9 '% +> ?*%&' 1%' ++ 3' ? ' *- % "/ /

1$%*(9*+"Q +%*'- +%*R*4% )&

), '&%&>)',* ("B*?-, * %&*' '@' ' "8&' '%':+%' "

1'9%&'-:?',-:?

"'''%1$"9SQA?T*,MEHHUA/:O / 9M OD"+

')'9%>>*/'')*B E*)'E B!9'%

%&* )9 '4%BD %$',BD-:+@'

(!'1$"9'','' *1JP'',,$ -$*',-$*

D%&&&M/OD')JP'D* *) "4*$')*B G* /*B ?4$'8 *1JP'',,

%9 (&'$D ! 1%'D 1%' !'*/%*&')'E %&, /%%&, )'%&, 1% % /& &' ' &,4, '' &'

'%9-*BJ&%&' B'$4

>)''9,' 9*1'

&%9B

)9**1'*$')

%&9$' 4$' "')* >)*,*/ * * ) <,)'= &,$, '&$

&9 %'D (/D (D D ' &, "+ 1 *1 >+*

E

79/, /,

+,9 'J&%&' M OD J&%&' +%&$'%&P M- OD 'E' ? ', D + - K ? K ', KD %&' 8 ()N?:-5

+%&%&I+%&89 %$' '$' +*)9(+M!'O '%+ ,,%

+) %&'9!, %&&&*';)7)''*B'''%&')1

>$' !J B@$ 8 +*7' !% /+ 8 +*7' !,&,

%' +%&3'&1'' " %%'' 1*!@$J') L F+G* +%'

+)'1$"9(%+B&), 0',+(%&%9 *2

(65)

@/C:(5M'E%& %&3ED3',')(E'',', E 8%E')O ', ME%& $'D 3',') !*8 ',

@''%&'O3,'',!/&$M+E,O$E)'H

"α 1$%*(9!*Φ.%7∆-∆%C%-,-AN∆M*OC5NC)0)B M+O',-'1

>- ')'9!*%∆M*&,+*%(/OΦ.%7∆-∆%C%-, -AN∆M*OC5NC)0)BM+O',-'1

"*-$'+E'3,')3''',-?N?:>",&*

,E'M)'H -NN?OH

!

+3'%&','))$' 3,'J')'','%&',,'')$''$

HM-N.NO',+$ HM-N.NO&)H0)'))'%&'%&@',' )'' ) )@P ,' 1',)' , $' $)%&' $'H 1'%&'%& @', >)'' 3,' '%& & E)') ', ,%&

'M(' +@)E'O,$''')M@O'%& 3'''%&&

$'J)3,'H

! "#

(*,!8-,3,'-)' )"*4 -) /'H)J M8 (*' 3,' E@E%& - ) ) E))$'OD ' $ -?6/ - 5$''',%8A'H %&,$8&'J'''E"') ' +',:*' '%& %&,' '$ E))$' 3,' MEH(HK):%',B'%'O

Referenzen

ÄHNLICHE DOKUMENTE

Juli 2017: Beginn der Strukturierung der Digitalisate in der ULB Bonn und in der ULB Münster.

hoher Druck, hohe Temperatur 2) Catalytic HPHT Synthese:. hoher Druck, hohe

Für jeden OLAP-Würfel und jede gespeicherte Sicht auf die Daten können Rechte an unter- schiedliche Benutzergruppen vergeben werden, diese Rechte werden automatisch für

Als mitten in den Semes- terferien klar wurde, dass das Sommersemester 2020 nicht in gewohnter Weise stattfinden kann, war die Unsicherheit bei allen Stu- denten – aber auch bei

In der vorliegenden Arbeit wurde die Expression ausgewählter mRNA-Transkripte im Rückenmark von FGF-2 knock-out Mäusen untersucht, wobei im Vergleich mit Wildtyp-Mäusen

In den G3mTerc-/- Tieren kann lediglich in Leberzellen eine signifikante Abnahme der mittleren Telomerlänge in 12 Monate alten Mäusen beobachtet werden, während Niere und

Universitätsklinikum Bonn, Gynäkologische Endokrinologie und Reproduktionsmedizin, Zentrum für Frauenheilkunde und Geburtshilfe, Bonn..

Abbildung 20: Vergleich aller untersuchten Patientenpopulationen nach den Zellen mit aktivierter Kaspase-3 als gemeinsame Endstrecke der Apoptose für die zytotoxischen