close

Вход

Забыли?

вход по аккаунту

?

en fr Study of viral and cellular factors involved in hepatitis C virus escape during liver transplantation Etude des facteurs viraux et cellulaires impliqués dans l'échappement du virus de l'hépatite C au cours de la transplantation hépatique

код для вставки
!""
#$%
&
#
'
$
&
!
(#$
)*
+,
*
-.+/
0)
0*
**
*1
0+2
10#+
*3
'*
45
6"%
(0()
7
#7
%
8!!#
(9*
7
"!'7
5
8#"8
()
7
!7
$#%!#
*)
'7
"!'7
1
1
/LVWHGHVDEUpYLDWLRQV
αSMA : Smooth Muscle Actin α, alphaactine des cellules musculaires lisses
EAE : Experimental Autoimmune
Encephalomyelitis
ARN : Acide RiboNucléique
EGF : Epidermal Growth Factor
BACTH : Bacterial Adenylate Cyclase Two
EGFL7 : EGF-Like domain-containing
protein 7
Hybride
EGFR: Epidermal Growth Factor Receptor
CD3 : Cluster de Différenciation 3
EGFRvIII : Epidermal Growth Factor
Receptor variant III
CD4 : Cluster de Différenciation 4
CD31 Cluster de Différenciation 31
CD133 : Cluster de Différenciation 133
EGR-1 : Early Growth Response protein -1
eNOS : endothelial Nitric Oxide Synthase
ERK 1/ 2 : Extracellular signal-Regulated
CDKN2A : Cyclin-Dependent Kinase
inhibitor 2A
Kinases 1/ 2
CHO: Chinese Hamster Ovary
FAK : Focal Adhesion Kinase
C-KIT : V-kit Hardy-Zuckerman 4 feline
sarcoma viral oncogene homolog
FGFb: basic Fibroblast Growth Factor
C-MET : Met proto-oncogene, (Hepatocyte
Growth Factor Receptor)
FGFR1 / 2 / 3 / 4: Fibroblast Growth Factor
Receptor 1 / 2 / 3 / 4
FlnA : Filamin-A
CPA : Cellules Présentatrices d’Antigènes
FLT-3: Fms-Like Tyrosine kinase -3
CRMP : Collapsin Response Mediator
Protein
CUB : Complement binding protein
homology
CXCR-4 : C-X-C chemokine Receptor
type-4
GABRA1: Gamma-AminoButyric Acid
Receptor subunit alpha-1
GBM : Glioblastome Multiforme
GAPs : GTPase-Activating Proteins
GDP : Guanosine DiPhosphate
DAP12 : DNAX Activation Protein
GEFs : Guanine Exchange Factors
DCC : Deleted in Colorectal Cancer
GIPC : GAIP Interacting Protein, C
terminus
DLL4: Delta Like Ligand -4
GLUT-1 : Glucose Transporter -1
GPI : Glycosyl Phosphatidyl Inositol
GSK-3β : Glycogen Synthase Kinas-3β
NEFL : Neurofilaments
GTP : Guanosine TriPhosphate
NRARP: Notch-Regulated Ankyrin Repeat
Protein
Gy : Gray
NRP1 : Neuropiline-1
HDAC7 : Histone Deacetylase 7
NRP2 : Neuropiline-2
HER2 : Human Epidermal growth factor
Receptor-2
NF1 : Neurofibromin-1
NFAT : Nuclear Factor of Activated T-cells
HGF : Hepatocyte Growth Factor
NG2 : Neural/Glial antigen-2
HIF-1α/ β: Hypoxia Inducible Factor α / β
NIP : Neuropilin Interacting Protein
HTLV-1 : Human T-cell Lymphotropic
Nr-CAM : Neuronal Cell Adhesion
Virus type 1
Molecule
IDH1/IDH2 : Isocitrate Dehydrogenase 1/
2
OMS : Organisation Mondiale de la Santé
IQGAP : IQ containing GTPase Activation
Protein
OTK : Off-track
ITAM : Immunoreceptor Tyrosine-based
Activation Motif
PAK : p21 Activated Kinase
IRM : Imagerie par Résonnance
Magnétique
PDGFA/ B : Platelet-Derived Growth
Factor A/ B
PDGF-BB: homodimère composé de deux
Platelet-Derived Growth Factor B
JNK : c-Jun N-terminal Kinase
PDGFR α/ β : Platelet-Derived Growth
Factor Receptor α/ β
L1CAM : L1 Cell Adhesion Molecule
PAI-1: Plasminogen Activator Inhibitor -1
LARG : Leukemia Associated Rho6GEF
PDZ : PSD-95/Dlg/ZO-1
PI3K : Phosphatidylinositol 3 Kinase
MAM : Meprin/A5/µ-phosphatase
PKC : Protein Kinase C
MAPK : Mitogen-Activated Protein Kinases
PKD : Protein Kinase D
MBP : Myelin Basic Protein
PLC-γ : Phospholipase C-gamma
MDM2 : Mouse Double Minute 2
PlexA1 : Plexine A1
mTOR : mechanistic Target Of Rapamycin
PlGF: Placental Growth Factor
MTP : Membrane Targeting Peptide
PTEN : Phosphatase and TENsin homolog
pVHL : von Hippel-Lindau Ce
Ras : Rat sarcoma viral oncogene
homolog
Raf : V-raf murine sarcoma viral oncogene
homolog
TGF-βR I / II : Transforming Growth Factor
beta Receptor I / II
TIMPs: Tissue Inhibitors of
Metalloproteases
TM : Transmembranaire
TNF-α : Tumor Necrosis Factor-α
TP53 : Tumor protein p53
RB : Retinoblastoma-1
Treg : Regulatory T cells
RMN : Résonance Magnétique Nucléaire
RnTPSNC : Recensement National des
Tumeurs Primitives du Système Nerveux
Central
RON : Récepteur d'Origine Nantais
TREM2 : Triggering Receptor Expressed
on Myeloid cells 2
TsAd : T-cell specific Adaptator
VE-cadherin : Vascular Endothelial
cadherin
SDF-1α : Stromal cell-Derived Factor-1α
VEGF: Vascular Endothelial Growth Factor
Sema3A : Sémaphorine 3A
siRNA : small interfering RNA
shRNA : small hairpin RNA
Shb : Src homology 2 domain containing
adaptor protein B
SHH: Sonic Hedgehog
SAPK1: Stress-Activated Protein Kinase 1
SEA : sérine, acide glutamique, alanine
SMRs : Small Multidrug Resistance
proteins
SOX4 : SRY-related HMG-box
SYT1 : Synaptotagmin-1
TCR : T Cell Receptor
TEP : Tomographie par Emission de
Positrons
TGFβ : Transforming Growth Factor beta
VEGFR-1 / -2 / -3 : Vascular Endothelial
Growth Factor Receptor 1 / 2 / 3
!
"#
$%
!!!&!
'#
!
(
'%(&
)
!
*&
*,!
!&
*,(
"
+
)
)
)
#
$%
!&!
'
--
!(
,
./$0
0 ,&--
1 !#%#-
1 %#
1 %-
2%
3-
"
+
)
+
( $
)
$
2!!!&
3
-
./$01
!'(!
!
.-
../$01
41",(!&#!
-
-
-
!5#!6
! ! *
+ ! ,
& -
. !
! 3,!5#!6
!!-!$71"$8
!!-
!6
( ! ' *
/ ,
*
0!1&
2& .&& ) -()/3(
*4
5
-()/3(%& & 4" 6 && ) $-()/3(
!
' 4 +&
4
) )
)
& !
.&&'!
9
!&:;<./
9
9
-##
!
-()/3( '!
. 7
4,
-()/3(
.'!& ,
6&-()/3(8
,
-()/3('!
,
-()/3(' !
,
(
$) 9-
,
*
-
$) :
& .
& ,4 4
-()(
$! $(
$)/3(
"
,
-()(
$'!
&) $
"
" -()(
$'!
"
6
' !
8
"
"!
*
!!,
"
*!!,
9!
+=
=
*
!(!
*
!
)=
+=
*
*
@
!
-
=
=
(
=
$
/9!
*
*
!(
(>
4, ?
9,
(
"
?
4
(A
4
,
?
?
!
"##$%
' (' )* '+ '* ' + '" )
(')*"+"'
"
'
)
+) * " ' ') )
',(')*' ' ' ) )
- ' ) )
'
!.%"!#.%! "##%""
'
' * ' + ') .
'
'+
&#.
- ) ' ') / +)" ! % !
" ##$%" ' " ) ) !
% ) !
% ' !0 .% ) " ' )
' !# .%" ' ! .%" ' 1 * !
' 2
'" 0 .% ) 2" ('
' +* ) ('
( ! .%
''+
*3''
' ') (' )* ! 4-% '5
'
6
-'
&"&7## ### +7 8 !/9 "
##%:'4
;'9') ('4)*-
!:;9 4-%',&"07#####+7'+ < != " ##$% '+ '
+ ' ') (' )* '
'
'+ ' , '
)'
!>
'"##?%
&
) ' ' +
' '
'" ' ) '(')*!)
&.%
!
' &# . ' ') ('
)*)
'?
#####+
(
/)
&###
)*5"
,&"&
## ### !?" '' " ''% -8 " 8 " ' ( '
!*"
#####8<
"&
#####8
)&%
@,&#"
*'"
)'*'?"A
#####$&$A8
''
$"?
#####$#$8''
B
#&,
'#
&0.8
''-
' A *' ! * '
"
1"
"?8
''"8
''!=5
"#%
"
/ ) ' * ' ) -=(A?C
AA!C/:4>@[email protected]=4"AA%
##$!
"##$%
?
('5
&& 5
(
& /
$33
B
!!
9!!
!
C
$!!
,
,
,
$333
!
!
"!
"!
,
,
$ 3. 7$B98
0,
0
!
*%&!
*%&!
"!
"!
$33
B
!!
9!!
!
"&!
,
,
"!
$333
!
!
9&!
3
#
"D
!
$33
B !!
9!!
!
C
,
,
,
$333
0
!
9&!
0
"D!
,7
$B98
C
C
#" $% [email protected]:":
"#%
#$%%&'&($)&*+,$-).,/(/##0#$&-/
'"
"
,'(
'
)
'''
' ) *' '+'
'
'
)
+
(
')
(
'
'
(
(
' ' * ( ' )*(
(
'
(
',('
')
('
/')*
D
#$%%&'&($)&*+,$-1-$2/
E '
)'"
)
' , F " ( " ) '
" !#%
!F
' )" ' + '' (
' (" G
(
' (' , " '" ' ('+(
- ' + ' (' + )
) ' 3 ' / +
) * ' ' )/
)'8'#.,&#.
'+8
$
!F
B&.
'!G
7#####+
%B'H!1'*
#%
- ' ) 3 '' '
I+J" ' + '' ' IJ '
(''"
'
)' !''7%)
+)
)
) ) )' * " ' ''
' C?$" +' '
( "0 . !KL'
" AA?% '
[email protected] *' ( '* ' ("
)'
(
''
)
'
(
' " (" ' ('
+HB)
'8H
')!BBB
BM%
(
'F
(
' + " ) ' , '+ ) ( +* + + - (
' ( ' (
(
''
(
*'#.
(* '
( , ) (
' +
" +
' ) ( *
+
)
')
')
')
(
' ' '
' (
'
(
'
+B
"
')
'
(
)B
'
0
- ' " '
'
'
(" + " '+*/
'
"
,
( ) EEN (
' EE+ , +
' / ' '
( ( ) 3 (
' '' ''
( '+ , '
("
(
+)(
''+"
B ( " " ' ''
' + ('
(
'
"I)*
( '+ '
' * '
(
'*'
'BBJ*
'
( ) 3 '3
'
'
!F
-
'
)'
'
F (
' " (
' (
'
B # . ' !: " #% )'8)'
(1&
* #"??7### ### + 8 !="#%B))
)
,)
!
'BB%"
'
-
' '
' "
)/"
'3'
"
) *3'' )" +
'!BM%3')
+
"
+ '" ' BB - )
)
)(
"
!0".*'
%
,
-
'
A
B ! # #
# # # 7 %
-1
# &' @=##
)8
),
('B
, )
+) ) ) 8
! (F
@
+
''
'!6=%"')
(/5""A?7#####!="##%
+
6
"7#####*/O6=
&#
. ' *" ) , )
### 5!P
"#%+8''
) 1 1 ' )
? !
% +
'
'8
''!"&
''%
- ' (' )* ' / *'
)")*
"?./
'8
)((
"
)
(*)
'*
(
+"
'"
(
' * ''
'
"
6=
' '8
,
"(
*)'
(6=I)J
IJ
##$
)
6=IJ
I)J 6= '"
'
"
+
'
6=-
)
)
+
, )
' , )
')+
'F''*
'
'"
)
("
'('*
6=,
+''
'
IJ
6=''
'
)
6=,
'
"
(
'
+
'
#
$
*(>
9!
(
)
' ;<5' *
$
$
! *
/
2
9!,
/
) " $ @@'
L#6
+/
9
H
6=,
6="
,+
(
'"
(
'")'
('
6= " +) (
' , 'Q '
3 #$%%&'&($)&*+,$-#*($#&%$)&*+
' ) 3 , ''+ ' ) !% ) ! %
!
)%
' )
' ,$#.
)8
' )
' ,$#.
)8
)
"
+ ' '(" ' '' '
" '' '
$(#$%%&'&($)&*+2/$&+)/++/
/ 5" )
(' @ !'
" ###% / + "
" / ' )
)
'
'
'
@" * F (
' ( *
+)
F
[email protected](
6=F9(
7
@) " @ (
'
/ R , ( ' ) ' ' ' 3 + ' +' ) +
'
' ) 3 '' ) '
'"
','
,
+'
&4&)/%2/%(#$%%&'&($)&*+%
- "
'
+)
+H)"
*)+'3'
+)
'3' , '3' / " '
*
"
( ' )
?A . !-
" AA$% " ')
+&#.'3'
'3' +
! " AA?% 4
)
' , + +
'9
"
+ + * +
*' ) ' , ) * +
))'!68"AA%
"
'+")
'
('
*
'
@H
" '
' )
/ + '" ' '
!- 6
' @ : 42
L" ##0% + )
" ' '
+')'
) ' "&E
++=5EF=5+
,33
*9:EE)=5
&333 *9:EE=5
$,$B9*9:+EEE=5
4
'+
* "# & ; F;' )
(*'
),
@L"##A
)+%
)
,-
('S')
''
'
('-('S'
' +' '
" + *
!
+' '
)'%" (
1
)
'* 3 ) '* ;
('S' '
)
' , *' '
' ) ' :
!B:% *' " + ;
'
/'
9
!;/9% ' + @H
' ' '
'3'(
+
) ( " ' )
)
)
' ) ) *'
) .,
)F
1 F H '* ' (
''*
' ) ' 9)'
F
)')+
'
9 * '
!'
%
)'
('
F
'
'
''*
*'3''
(
'
'
F)'
))!
*%
F
'
'
'
' ' * ' +
'(
'
6;
,)
86=
' ) L( ;'
8
' !> " ##&% '
B> '+ 3 +
( '
! "
##A%"!T"##A%
* /
* !
5
-
'' " ' )
, ' - ) , '
' ( - '
)
S ( " *
( ' " " ' ''
'("
' ( ) " " )
'
B'
*
'
'
) 9 " ' ''
)'('
'
+ (
'+")
*
'
9,
9(
.
4-
."
.1B
9
!!!&
9$9*
*%
24
0. B>U B
(
B>U B
(
''7U '' 7 & +
'
[email protected](L+
;9&U'
&[email protected]=7-U
( L +
@7=7- :=U +
' -C7?U ( L 7?
--4U(9BCU
L9;/4U
'
@C;UM
L'('
')
'
';:U' '(:U
'
) '
45U +
' :U M ' ' ) '
@9CU '
) L 9-U
- 9C-U L - /65:U
'
2
965:VU)
2
VM/65:U)
2 >65:U ( 2 -CB;U)L >(PL' ' ) '
6;U #?'([email protected]'( [email protected] :":"#%
9 ' '" ) '
'
' "A"#""$"A"
'
'$!:"AAA%"! 'WL"###%"!:
" #% - ' + ,
' ) )
' ' H
' ' ) !
0% ' )
'
!
'' )
:@9C [email protected]';:%" S(!))
;9&:=!
+
'
%" ' )
M/65 !M /
6
2
5
% !W " ##$% )
'+
' !8('
*(
(
!B>7B>%%"!LC"##$%
2
.
'
'+
''
- S , ' + '
)
'
"','
"
'
@H
*')
1,
("
)6='
)'
) ' , '
! " ##% !
1+% *
/65: 965:" '
9;/4" '
' #" '
,
BM"
(
)''
;9&
!LC"##$%
9
6=
)
"
'
' '
)' )
'
) ' ) ( '
* 9 *'" '
(
!B>%
)7
'BB"BBB
,
'
6=
"'
)
6='!9
"##0%"!4
+2"##A%
&
0
5++
2
' 2!#(
!
!-
!
= 0
5 [email protected]
[email protected]
0
5+++
5++
5+++
?"@A
?4"@A
!
!
?"@A
?"@A
9
() 932;
"2$01
9"
"34GH10
""*/4
/-&
-
!
##;30E
"3G"2$01
/ -'/$01
-;/1
/-&
-
%
#
2
9
'/$01
""*/4
"34GH10
-
##
4(;;
-'5 940
9
*"
9
"*/4
-9/*E
2;3
##
*4040B
>5
!
1$&# ++')
(
L
!/65:965:V%
)
&
)
)')
:=)
'+
'+
'
'
)
45U
+
'9;/4U
'
9BCU
LU''&+
'
'U'
'
;9&U'
&[email protected]=U(L+
@7=
-CU(L:=U
+
'->:U
'
'B>U
(
B>U
(
'U'
X6
,)'
'
Y
'
'
8(
@!:"#%2-
'
+
'
!ML"##%
)
,9
"),4"+,-
,('[email protected]+
[email protected]"@:5U'">B5U>(
*+
>>U
>
"/;U>
(
2
"-U-"->BUL;45U'
"
45Z=U
[[email protected]@
"#% ('
B>
)
''
)
)6=
46
!9
"##%+'
B>
)
' - )
'
;9&
*
965:[email protected] )
' '
BBBBB) +
6=
!
"##?%
>)5
'"
('
)
'
)"+
9*'"
A
A ) / ) (
" )
'
'
*'!WL"##?%"!B
:
;(
(
6
;A#"##?%
,
)
'
(
!B+ " ##&% '
;9& " " (' ) ( ( ' ' B)'"
)
'
6=" ' '
' #" [email protected] '
/65: ) & . 6=
' &# . " '
/65: ) *
' /65: ) ' " /65:)BBBQ 6='
@" )' ' ' ' ' '
- ) ' - 6
'
@ ) ' ' '
'
''-
+
,
+'
!-6
'
@ : 42
L" ##0% ) ( 4" 9
"
?
- ('* !
12% !ML " ##% *
'/65:
(-"'
45
(
(('*"*
96:5V
,'
B> ( 9
( 4 *
'
*
''
4/5
!4
'%"
[email protected]=:@!6'''
+(
+% T;! (
'
%
* "$
' ( )' '
+ (
!
" ( (% / '(')*'
'+*
),.
' '
- ) 3 ' '' - ! " ##+% ' ' + ' * '+ !"#%"!;
"#%
)',
'
' '
'''
S
-")
! >>%4
'+3'
',
!-'"##$%"!9
2"
##&% )
' '
'')
K7\
,(
L
M/65"/65"565+965!M
)"##?%
- )* (' )
' )
) - " +
)
'
+"
'**
*
' ) '+
)
!-+ " ##$% - ' '!>P8"#%
$
6 7
/"
!!
/
99 9,
,
*
"!
3 4 $% + )
F
!/9-%
)'
H,')
!/-%
, '
)* 2 +
' , )* *F F ; ) @-'W"# *) & $% '
)* + )
+) )
' '+(
!: 5''" AA&% '
'8!
3+%'
+"
'' '
D
")
) ' - )
' ' " * )" * +
'+(
)
' ' )* 7) S ''
! 2K"##A%*'
'
)*
I !+
'
% !
32% ) '* ) H
'+' * )* H, ' ' ( '+*
+ '' '
'*)
'
'*
(
*'+""'
8
*(
''
">B5V
!>(
* B+ 5
V% (
*( +H +(
M> !)
>% , ' '' '
* - + ]
'
>B5V ) )
3 ( ' ) >B5\ ' ' )
*
+,(
*
''*'
''+'M/[email protected]"="-""/%!5"##A%" 5V
-^-: !P8"##?%
)*
)
)
*
(
*]
)' )
!
5+% D
+ *' ' ( )" ,H
M/65)
) '+ )
'
' ' * )
) , '
9
) '
<
) * " ) ) " ; " ) 0
"I
>
1799"8
0*
0!&
2!(!
.&
0-
"!,!E#
-#7./$08
9
> B
0%
1!
$(!*
,!
!&
0-
/6 1
!>
22& ' *&(!
9#
B
##
(
0
',%
9!
0-
2! ,
,7*39"E"38
52 # #6 /
'
'
+ ;2/
L
; " -
'
" M/U ) " 9U
'* '
" M/65:U ) 2 " U L " 4:9U
" >B5VU * + " ;9U ''+( '* '
" 96-VU
9
*
' ) '' )
" M/65U ) 2 "
565U +
+ 2 " @U " -U - " 965=U ) 2
=" @U " 4:@:9U L( " 965U 2 "
/65$U /65L '
$" 5U ' ) " ;B9U ; +
'
"9U'
)
+
"9>U
((
*(
'
";U(
L2B/65
'
(
'"965:\U)
2
\
!4:9% +H '"H
S'
) M/65" 4;->" [email protected]/ ' ' !
52% )
; )
' S )" L " " ) )
' ' )
'
'' 4
"M/65:"
K4;" 4:@:9 !4
: @L( : 9
%" 965 !9 6
2
5
%"565
/65$!-'W"#%
5' ) ) ' + !
5"% )
E
!
'
6
'
'
% 965=" D " ;65\" = 4
)
,
)'(+
";B9
!; B+
% [email protected] !9'
@)
B+
%
S ''+ +" +
H
)
+
'*
' )
'
'
H
S 9 ' )
'''
"')
3'
)* )
/ )
)*
'
)'
B ' '' * '
)
'
)
)* * !
7+% -" '
) ) ' , )
' )
'''")++)*+
'"
*(,,
&### _' !;>B4 4 6:@T" A&&% -" )
(
* '
'
(
* >B5V
!
%" !> 5
L'"AA?%B'
'
(
)
) - )* ) '' )* *"
" ' + '+
'*
'
"
)*')
)()'
A
2) 9- -#-!-
2 && '
(
!(!
#-!-
7 4 + '
)" )
) * 2 '
) ''( / '' , '
+ ) " '
, ( )
(
-''''
'
)*@-'W"# '
) ' , '
)* )* !- " ###+%
'
'!/>"##%"!:
M " ##% '
'
'
+ '' )!
!
72%%
@H
" ) '
, '
)* '' ' * '
( ! "#%"!
7"%-+
)**'
- M/" ' " ' 965:\" V @" /65: M/65: S ' '! ("#%
0
#
0
%
'
+
'
'',
' ' * + '
)
H
, '
'B*''+
+!
%'
-' !6` K% -' L( +
'
))@4(
* ' L( ' 3 ' )
'''
')
'
,"A'
!K"##%
! "##&%'
'
$#B
!) )
' ' '*'' H% , ?# 6( !6(% ' '
;'
8
' !
'' ' ;'
% L( - ' ( H
" '
H)
+'),
)';'
8
'&H
#
'
( 0H
-
'+
'
'
'
)! "##&%-'
'3
')
),
)
+ 7
) 7
'
)
'
0 #
- )* ' ) 'H )
+ +
' '' '
'
- + ' ' '
*'
' + ' ( '
'
*'@H
+ ) 3 ) - ) ' , ' )
' " ) " " '
+ ) ' '' 'M/65"
D
965
" ) '
*" '3 *
+
)
H
'
H
=)8'+ [email protected])a '' +
:
% '
M/[email protected] '
* + '
' '
) ' 9 *'" ' + ;8'+ !> '' 6%" + >/: ' '
' ( (
L + ' + * " ) '
+ '
) ) '
)+ B
4
b30"(EC,
b;!,!
b"
,
4!
b30",EC(
b2!,!
b9
,
2
3!&
b"
b4!
8 9%
+ : ) 'F ( + + ',
))*
2 )* '
* '*F * "
'M/65"
)))*
(
' '
)* !
"# " '
F ' )
+ + " '
) / ")*
(
* ' '
'
- )
' )
+'@W"##$ )
''6++'/65:
'' + + /65: >/: /" '
) '' 9C- !KL " ##%" ';: !6 " ##&%" : !K' " ##?%"
:!4
'"##%+
0)
9%
'
'
5
L'A$!5
L'"A$%"+
)*
*
)
' '' )
'
' *( +
'
)*)*
'')
''
"
)
(*
'''+M/65
'*''+ -"
8 " ' '
3
/ " '
)* '
'
'
''
'
!
8%
S + ' (
)
)
'" " @ " '
++)
)
) ' )+
'
)*
+
*'
-
)
8
(
*(
*
)
)
' '
'
' + " ''
7
''
)
'(' , '
'+
' !K
>(" #%" !C "
#% " (
* +, + + '
+
, +
''
)
'
'
++
',
'
)
'",
")'
' B' + ) ) " I
0
4
(!
9
I
,
(
0
4
$ # $ $
+ M
'H + 2 M
'H +
' + + @U
Q +565U+
+
+
2
QULQ/65U'
2
Q/65:U/65
Q/:CU*
LQ 565:U 565 Q >@-U (Q >65U ( 2 Q [email protected]
W LQ :9U Q @9CU '
) LQ /CU '
)
L LQ ';:U ''' '(Q 4B-U 4
'[email protected]:9U
([email protected]+
%
('Q965U)
2
Q965:U965
Q9-U
-Q
9BCU
(
LQ 9C-U
L -Q:;CU (
LQ >>U Q
;@;U)
QM/65U)
2
QM/65:UM/65
@;L"#
'' )
+
'
'
' ' + +
'
')
)
!
+%=)8'+
" ## * /O ) '' '
*"
'
""
)"
+
+
'##A//
+H
BBB ' +
' ) '
'' *' +!+
M/65:"965:"C5;%
M+!'
'M/65:7"'965:C%
)
+
'
'
' ' ' ' , ' +
)
)* '
) + / " '
'* +
' ' '
)
" '
)
!:+ " ###%" !CL " ##% )
)
,*
M/65F 965" 965" 565+" ;45V !'
%" L" "
"/;
M/65:!
/
)"##A%!;
'
"#%
5'"
S
'"
) , , +) '3
'''')!) 0*
#$
3' '
)" )*
'
',
'
! " ##?%" !=
" ##?% - ) '' *' ) !
'3' %
'
)+ , '
, +
' )
)* '
''
:AA#A$" + c ' )
4
M'
+" '
+ )
>> )'
+
')!
2%
3' ) H
'')
'
'
'
@")
)
'
( ' '
-
'+
'+ + '
*' '+ '
F'
)
'+
+'''
'
F
" '
7)
' * ) + F
*@
'
)+
'
)+
'
)
' '
'
B''
+
'+
'
'+
@69B
'9 B
-F
'+F
[email protected]/%
F $ '
'
' '4'
/
'
)"
'9 B!9*"
'
" B% '
) ' 4' \
'
' + ) , ?
'
''+
'$
,''+
69B !(
(
(
% & '
'+
;
'
)+*&
?
'''
[email protected]"##0
9
'
'' '
'
'+)
'
S)
'
"+
+
''*
)
'
' ' '
! "
#%9''
)
'*'"'
'
!4" /" '
% ) '
S'
7
'
!"#%"
!9"##%"!;'
"#%B"H)
')++
'* * '' )
7+
' ( ' '
" '+ '
+ ''+
' '+* (
!:
"
##A%
: 6 #
#%$%
9
'
'
' A ) 0 !6
' " AAA% ) 8 )+" ,$8)+08)!
%-'
' )
''+F'
?/!;"#%
'
)3"'
"
0" ''+ '' '
" " &" ?" , ''+69B!6(
(9
(B
%
'
$ 3' ' " &
'
)'*
'
)*
)F $ @4C"##0
'
"""$0
'''
+"
& '+
" ' ' + -' ) ' ) / ''" 4'" ' &## ' ' ' - ' ) '
' ) !5 "
AA$%"!C
L"AA%
' '
')\'*
[email protected]
" ##%" !
) " ##%" ! " ##% - ' ' ) '' /;" :4 * -
'
+
!C
"AA$%
'
+ * @ " ' ''+
3)
'
"
?H
S'3''"
+
'++ , !>
" AA?% '
)?
)
'
'
)
* !C
' " AA0%" !W " ##%" ! "
##%"!4
"##%
' " '
+ '
''+ ) ' * *
!
)% B * *
, '/
!%*'*!9*%)
'
+!-)"##$%
!6"##&%
'
? ' ) * ' @ '? * *@ !9*@% '
('
) '[email protected] * 9*@ !: " ##0% ' 9*@ !:dL " ##0%" !
L " #%" !L ;
'
L"#% '?='*9*@! "
##&% 9*@ !;2(' " ##% '
& **'=/" '*9*=H
S)
!6
"##%
*
!"
##%'*=' '-!
"#%')
')9*=),*
'&@ H
S )
' *
[email protected] " ##%
?
/
/
/
9,
./$0
./$0
./$0
./$0B
./$0
./$02
./$0/
./$00
"$0
./$0
./$0
./$0
./$0
./$02
"$0
# F / 6 # (!
+
* '*,9*-
'
('!-++9
"##&%
B * '+ + '
'* * - ) )
'+
'
!
& 6C
' M/65 $ M/[email protected] H M/655 965 !-
" ##%" !
L " ##$% M/[email protected] ' ''+ , )
) A0A !5 >8"
A0A%"!6
28"A0A%B
''
* , M/[email protected] + )
'
$ ' !M/[email protected]" M/[email protected]&" M/[email protected]?&" M/[email protected]?&+"
M/[email protected]"M/[email protected]"M/[email protected]#?%"!>
L"AA%"!9
L"###%
M/65=
*
'
')
M/[email protected] !
" AA?%" !
" AA?+% M/65- M/65
' + ) ( 4 -
'
'
''
)!W
L
)"
AA?%"! L"AAA%
M/65/
')
)*
' !( " AA%" !( " AAA%" !K " AAA% ''+'"M/655"
))"
'*
M/65?& !T'8L " ##&% e 965" '
, H
' !
" AA%" !> K" AA%"
!
"AA%"!-
"AA$%
4
!4:9% + M/[email protected] !9 " ##$%" M/[email protected]?& ! L " AA0%" M/65= !L " AAA%" M/65-" M/65 !Cff " ##?%" M/65/ !K " AAA%" M/655 !T'8L
" ##&% 965 ! " AA0% !# % 4:9 M/65
@&"M/[email protected]?&!68'9
L"###%"M/[email protected]! >
" ##$%" M/65-" M/65 !Cff " ##?% 965 !68'
9
L"###%
$
-
)*9
*'" M/[email protected]?& ' >=" !> = '% * , 4:9 ! L " AA0%" !9 " ##$% ' 965+ M/65=?& ' ' , '
, M/[email protected]?& S ) 4:9
!"AA0%!'L"##%!MC
"##$%
-
' * '
" ( , H
M/65 * *@ M/65 *
' ' H + M/65"
)'++' 4:9 7
M/65:
'
4:9,*
965== !
'
' '
* 9) 2 =% ' !=H " ##?%" '(' ! " ##% ;65\ S (
''('
(;",
4:9!6L9
''"##0%4
'
)>65! "##0%
565!"""$%
!K"##&%''+"
'
)'
'
''+
!T
+"#%
!>"##0%
#%9
3D
57$
'* * ' '+*
)
' '
(' )* S '
*
'
)'
)
!C
L;)"#%'
S
*
'@
S
0
*
!
" AA% -
S + '
('" '
" * ' (' ''+ ' '
'
'=" - '5 '
('
'/'
!:"###%-
*'
*
4:9/"4:9
*' ' ('
' , 4:9
('
'@,4:9)
'5'4:9!-"AA$%
'*'
+
'
'
S
'
'@ '-
)4:9"4:9
4:974:9!"##%
*
'@'
)
* !6
5L" AAA%" ! ) " AAA%" != " ##%" != "
##% S 8 '
+ *
-" '@ '5
'
g
)
, )' ' ! L 4" ##%"
! ( " ##&% 4:9 *' '+(
! " ##%" [email protected] " ##% , ! 28 " ##A%" !6 " ##A% '+
)*'
'
''
'*
) '" '" *
*
" !K'( -" ##?%" !='
=
" #% )*
)
*
'
(
! -
2" ##% ''+ ' *@ '
' ('
)* *' ! " ##$% ( '
(' '
!=
" ##$%" !K'( " ##0% 9*@ *' *
, '@ * '[email protected] ?= ! " ##&% /
*
" 9*@ ' +
' *
!="##%) '5+
*
'
!; " ##A% B * '+ '
" * 9 *'" *
' 9*@ +
A
S '@ !;L " AAA%
-" *
' ' ) 9*@ '3'
, '@!:
'"###%-'
*
'@ , ' +
O *' '
'*
'9*
)
'
*
'
!9
M " ##A% <
4:9M/65:)
)
*
9*
!-)"##$%"!=
"##%
) ' '* 4:99*@ / '
'
*'
,
)
!5H"##%
*' '@
H
S
'
) !H " ##?% )
( ' ) S '
( )
' ! '
"
##%"! L("##%"!; "##%9'
" g '
( ) ) '@)
''! L(
"##%O'
*
)
'
'(
!K'"
##$% O '@" 4:9 9*@" ( *
' ' '(
* '
''(
"'
'@
+ +
' ( * '(
!9
"#%'S+"'
( ' + '
!K
2HL" AA0%" !K
2HL" ##%" !- "
###%" !- " ##%" !C' " ##0% - )
'@ + )+ ' ( !: " ###% S ( '@!-
"##%9''" '@''
''
+
()
' ( ' '' =9 !( = 9
%
#
'@ '
+
)+ ( +
' '@ '" ' ),
'@! ("
#%
;
'
, " '
' N '3' )
' (' )* '
'
3D
57 ' '+ ' ' 9 *'" ) (' '
)
!
"##A%-*(''3'
'
)
'
)
@)"*
4:9''
)
!5)" ##?%"!K"##%"4:9
'+''+) M/65:!=L"
##&%*
4:9'+
+
'
'
)* M/[email protected] !C2' " ##0% 4:9
' ) 565 ' '' ,
!K " ##&% 6 4:9 ) ' +
( 674:9 '
M/65 M/65: ' )
@9C !) L%7W4C !W 4
' L% *
6 *
' 4:9 , '
!>"##0%
4:9 ' '
)
' ('
)4:9
'
M/65 M/65 @" =" -" / 965" *
)
' 4:9 *' ) )*('!>8
"##%"!/'"##&%'
4:9)
')'+(
!
#' "&' H
% +) 8 C '
')!CL2"AA$%"!C2L"AAA%
C , ) !L
(' " ##&% *')
'4:9+M/65"'
'@"'
')
'(')*
' ' )
' (' ) ) ' '
'
')!6"##%-
)
' ) 8 C '@ -" * ) ' ' ) ' '
))3
! "##%-)*
)
+
'@
' ! % , '
* ' '
) ) *
4:9 '+ *
4:9 '
' ' &"&' H
)
'
'
'
)* '
!CL2"AA&%*+
'@M/65'
C+"
!
" AAA%" ! L " AA0% H
'' *
'4:9
!M " ##$%" [email protected]
" ##$% " 4:9 '' 'H M/65: , ' M/65 M/65: '
! L " ##%"! 6+ 9
" ##&% - 4:9
' M/[email protected] M/65: !KL " ##%"
! > " ##$+% * ' 4:9
M/65: ' ) H
<
'
)M/65
'*
! L " ##%" !9 " ##$%"
+) '
)'M/65!KL"##%"! >
" ##$+% O '+ (
'
'*+M/65!>8
"
#%
'
9P
'-'
, '
''
4:9 M/65:" '
'!9"##0%
'
' * " " '* '*
' ;
* *' *' '
N!;
(
LCL"
##$% '
'- 9*@ + )
'
'
')
H
!=
2"##%!C
" ##A%*
,
4:9 +
)+
''M/65
'
'/
M/65 ' + + S +
'
)*
)
!5L'"#%"
*
* ) '
!'
''
* ) '
D% ) '
)* 8 !
9*@
9*@
)!>8
"##&%
8+!
*'9*=
9*%"!'
"##A%
S*@')
'' '?
+
'(
!;
(
L"
##% '* 9*@" M/65: ;C '3')
'(
(
!;
(
L"
##+%'3'"9**'))*
'
8 !) P2 " ##%" !6 " ##%" !6 "
##&%8
8+!;
Mh88"##%'"
)* 6 !6 " ##&% '
'/ 9* S )
' ) '' 4:9 -
) ' + )' ' ' +
' '
+ '
M/65 '
'
*
9*M/65
'
9*
M/65
,
'
+
) +
)
4
7 M/65: M/65 - +
'- ) , '
9* , !C' "
#%/"
'9*
'
+
M/65: !5% * M/65!P('"#%
9''
64'
*
@
) / " )* '
+
:[email protected] *@ *@ ' 565+ M/65 ' , '
+ )
" '
'
'*+9*@M/65:9*@
565:!%''
(
,
)
/" ) ' ) S '?= +
!C
"#%
'+ '
'
'* *(')
+H
+ '
7
'
'
3D
57$
)
' ' (' * +
')(')*
) ''
'
" )
S'
)*'''
'
+ ( ' ','
''
'B*'
) ! '@% !4:9" 4:9" 9*@" 9*@" 9*@% ' ) *' S !6
'8 " ##&% 9*@ ) g ,
;:/!
*
'(
%!
''+'''
+%@9
[email protected]^ )
% ! ''+ , ;:/ )
% S '
!;L "
##?% ('
' 9*@ ' + " ' !>2 "
##?%
'
*('
" 9* '+ ' * +
'!C"##$%"!P"##A%
''
'
'
' S '
(C '@'
'
!6
'8"##&%" '@+
'
(
!L+
" #% :''" '
'@ S +
)
'
-
'@,4:9+
9*@,;:/!>("#%H
'@
)* 8 ' ' )
' '= , '
! "##0%
57 ' '' ' '
) @ )
"[email protected]%
''"
)
(,)('('
)H,
* ('
( ; ('
( ; ( ''
'
" * 4:9
,
''
")
"
''
('''
9 *'" 9*@ *' + ,
)
('
( ; ' (
!-
;"##0%"!;M"#%-
9*@,
) '
'* ) ;:/ @9 , '? !;L " ##?%
9*@ '
('
(' !;L' " ##% '
+ " *'@
)
,'
('
( !
('
( ;% )
' ! "
##$% '@74:979*@)'
''
+ '
'
( ('
( = )
&
('
( ; !T''
" ##0% <
, +" (' '' 9*@ (
L''
!K"##%
'
'
9* S '
('
( =
''
!>
"#%
('
(!-
"##0%
B'+
('
(;
[email protected]:9"+
4:9'
' ' '' ' ('
( ; ! " ##0% - '
4:9 ' ) '' )
('
( ;" S ')C
4:9! '
"#%
)+4:9('
(;-i
% , '
('
( ; $ % , '
; % ) ) /@/ !/*' @
''
/
'(%
4
'' ' * ( ('
( ; ; !
S ('% *
4:9 ; +
*
4:9 !T)"#%"!K"#%;65\
'
*
4:9
B?)
;65\''
!)"
'
%
)
'
*
4:9 ('
( ;
!K " #% O '
'
'
'
'*
*
4:9;
,
'
'
'
-
'
'
('
(;
'
S M/65 ' !> "
#%;'''
+
('
(
;'
''*4:9 '@!
"
#% - S '* 7* ' ) W ) '
'
*
?
5
$
/3(
2
3&
$
!
$#
72E+++8E
7CE++8
4,
!
706(E++8
5
!
$#
7!IE
++8E7GA6
++8
!
!
"
7(E
++8E 7B( ++8E7,
++8
!
!
#!
7E+++8E
7.#(JE
++8
!
!
!
9#
706(E++8E
7;E++8E
7"6(6E++8
!
#
!
$#!
7CE++8E
7B,E++8
!
2!
9#
7"6(E++8E
7GE++8
(!
!
"
#
7KE+8
#
!
3#
7;E++8
!
!>L
!
9#
7GE++8
9!
!
"
76E
++8
#)F 9 +
$
'* ' '
'+' ' > K+ )
+'+!>K+"#%4D)'",
)'
"'
)"'
++
('''"'
+*'
"
* )
)
'
) +
"4:9*'
'+'
)
"")! 8-+(
"##%"
""
)
'
''
+
'"
+
'!5L"##%"'!C"##?%"!9L
" #% '
' ! ' @L" ##% " *
)+
+
!#)%-*
,)'"'
' , ') ) - ' ! " ###%" !M)8 " ##%" ! "
##%"
'
!H
"##%"
)!"##?%"!=+
"##$%"
!9L"##%"
'
(!^"
#%
'
)
!>"
##% - * ' !=
' " ##%"
! " ###%" ! " ##% 9 '" '' ''
' ) +
" *
@:4 /
'
*
4:9 ) (
' ' <
6=!#
(
'BB)?6=%/'
)4:9)
'"*
4:9')) ')
*
4:9*)+"(
$
''
)
+ , '
) + , '
)
M/65: M/65 - $
' *' 4:9 ' M/65:" M/65: '+ '
''M/65:*
4:9'
'
)
>657 )
)
'
!' '% !> "
##$%" ! " ##$% " 4:9 >65 '
'
! "
##0%-
)''
4:9
'
'*'4:9-
, M/65?& " '
" '
)* '
*" , L M/65 , '
' !
" ###%
' + ) '
' *' 4:9 !9L " ##%" ' '
) ' ' *' 4:9" '
))
@9C!K(
"##&%-
'
+,'
!
L% '
'
- )
'
M/65?&74:97M/65: ' '
<
'"*
4:9
+
''O0$6
'' ) )' + " '
* '
S !> " ##$% + '
*
4:9 '
:[email protected] '
))
'
'
' !>
" ##$%
34:9
''+'
''
49:"
'+"
) M/65 '
)*)
')
M/65 '
) (" ' *
')*+ B
+
4:9+'
)'
)* ) M/65" +*M/65!9"##$+%
0
S'
'+
)*'
'''
*!-88"#%
'+
'@'+'
'
'
" + , )
'
!= " ##A% 9*@ *' !6+
)L"#%'
,
' ' !; " #% O '
^ )' *
' ' 9*@ 4:9)
'
!>"
#%O('
'
'"'
'
9*@
)
'
'
'
!=L " ##A% O '?
' (
M/65: <
9*@ - '*
'
)'
'
''
'3'
L!-
"##A%O
'
9*@)M/65:565:
+
' )
'
)!C"#%B'+
S * '
(
' '* , ''+"
'
,'3'
5'"9*'
'
*'<
+'"'"
')
'
'!:
L"##&%"!:
L"
##A% / 9* '+ '* / "
*
*
'/"
"
'9*+
'
' ' <
" '/ ' )
'
+ '
)* ' '
8 != " #% :'' * )
' , H
" % <
" g ' / '
)9*
" )* '
!-88 " ##%" +%
")
9*)>+=
+
)
'!-88"##%
A
;
,
'*
'
)
*
. 9
!4:9% '
, A0$ 1 , [email protected]&%
)
'!;L"A0$% '
, *
g ' *
*
! "AA&%B
* ) S ''+ '
'@!C
L"AA$%"!>;)"AA$%
' '
! '=" '-" '/ '5%!-"AA$%"!;L"AA0% ,'
*
,*M/[email protected]?&! L
" AA0% ) 4:9 + ) 'M/65"M/[email protected]!9"##$%"M/65=!L
"AAA%"M/65-!Cff"##?%M/65/!K"AAA%
')
''965!"AA0%
B ' * !4:9% ) '
-
( 6
' ;) !- " AA$%"
!C
L"AA$%-
""*'
'))[email protected]"4:9*'
-
=)',4:9')'
5)
*
!-"AA$%*
)'
@
'' + # , &# , 4:9!;L"AA0%-
''
4:9")*'
4:9M/[email protected]?&&"M/65-965!68'9
L
"###%
#
;
,
,$
(!
/
#
%
B
'+
*F , 9 + * ''+/
*
'-O=!
''+%!
'
%"*
'
'
*
MMBB!5M75MBBB%!
'
++%
'@!'[email protected]&7_
%
'
' 7 M/65 '
+7+" '
' "
4 C" ##0 2 >
'
'
' ''+ 4:9":
"##0"-
'
''+'
4:94:9
'
(6***6
>
*(
)
##L"
'
' * !)
0# %" '
''+ !& % ' (
' !)
#
%*.
'
!-
"AA$%'+ '
'
0#.
'''+!
*+%
-
' * ) & !
*+% ) ,
*'4'
'@"
*
'
'
* '' - - '
-O=!
''+
'
(%
'=)*
' + + '
* M MBB !5M7MBBB%
' H*''+ - @ !'[email protected]&7_
% '
)
'(
_'%
'
4'
'@
-' ' @ = / *
*
''3''
'M/65')
'=!4L'"AA0%'
'@
*
'@''*
M/65?&!6
"##%
*
'=4:9'
* '
* * !
"
AAA+%
' = *
M/65?&" 965 M/65-"!'L"##%"!6"##%"!Cff"##?%B
*
"
"'*
M/65
?& 965 , 4:9 !'L " ##% *
'
+
++!MC
"##$%
) ' +)
'
4:[email protected]
"##$%
' @ *
' '' '
'
/ " '+ )
' " '
) H
* + ' +
'@ " * ''
'
+ '
+
'
!4L'"AA0%"!6"AA0%!:8
" AAA% 4'
" '
H
+ ' - !4L' " AA0% / " '
'
' * ' '''+(
'4:9 ' '
'
'
'++ , * '
''+
,
-
'
'
)'!
*2<"%)*
'''
'
S
'
''+4:9",,''+''
' ''+ 4:9 * 4:9 [email protected]
'@ !4L' " AA0% - ''
) !- " AA$% )* +
'
'
' ''+ '
4:9
(6***6***6
!:
"##0%-
)
'''+N
'' S '
4:9" ')
,
+
'
'
"
'
'
,H
*
!-"AA$%!4L'"
AA0%@"4:9
)
)
-" + '
'
*/65:4:9
'
* * ' - '+ '
-'
/@! F"/F'"@F%!K"##%-
' /@
)^
,
''
) ' 9P !9 A&77P% 4B9 !- :"
AAA% ' 9P ' (
' 4:9 ) '
" 6B9- !' ( (
%"!M"AA0%)(4:9
M/65: !='>
" #% - '3' + ,
)
)
) @L '* M/6574:9 !K"##$%C6B9-
)* '* * 8 8+ !K " ##?% '+ ( +) 8 C 4:9 + ) '
(
' 4:9 8 + )
' ' ) !5 "
#%"+
M/65:
/:C
'
! " #% (
'' [email protected]
!5'@" % ' '
! "#%(
+'
'* M/65?&7M/65: !6
" ###%" !- "
##?% ' ) ' (
' 4:9
-8
''"
4:9
+
'
' # !#% B '
A *
? " *')&$L+-8
'
'0!:
" AAA%" !:
" ###%" ! " ##% ) '
+ 4:9F 4:9" 4:9" BBB4:9" BM4:9 !6
" ###%"
!:
" ###% !-L
2L " ##% -8 8+" '
*
4:9"4:94:9+!T"
##%!=
)L'"##%
'
+4:9+!%!=
)L'"
##%
4:9 + '
' !%B
'
*
?
&L+!
"##Q:
"AAA%B(*
'"?+"*
&3**
')"4:94:9+")
'3' ' )" 4:9!$%" 4:9!%" 4:9+!#% 4:9!&% O ' + ' !4:9" !:
"
###% -8 8+ ) ' * 4:9" +!T"##%!=
)L'"##%
:F
'B''
+
'C
0F , (!
M/65:
" M/65: + M/65: ) 4
!4:9% !4:9% )
9> [email protected]'
[email protected]"
#
-
''''"4:9
,
)
@
*
'+*
$
* ) '
B ' *@@ * ) ' '* '' 4:9 * +H
'!)
BB%
6C3
M/65" M/65: !5%" M/65: !C:75L% M/65:!5%)
*4:9!
0%
M/65: ) ) 4:9 !5 "
###%" + *
M/[email protected]?& 4:9 M/65: 3
''
'
4:9 M/65: 9 " '@'
+
'
4:9
M/65:!="##%'
))
@9L/:C70!="##%
M/[email protected]?& ' M/65: 4:9
+
4:9)M/[email protected]?&
M/65)
M/65:+
+
! L"AA0%'
"
+
''
M/65:4:9
M/[email protected]?& ] '
'* ! L " ##%" !4 " ##% - M/65 + ' '* ' *
M/65: +
!KL " ##%
4
' ) M/65: !68'9
L " ###%
) M/65: M/65: ) '
1F 9
' '* ) !4:9% ) 2 !M/65:%"(
L>
(
2
/;"
[email protected]"\*@"@"@"@4
,)M/65:"*
4:[email protected]@
4C"##0
!5) " ##?% M/[email protected] M/65- )
4:9M/65:
!5) " ##?% /" * 4:9 M/65: ) (
*
M/65- M/65M/65:!Cff"##?%
. '
[email protected] [email protected] (
' '
- ''+ ? '
''
+&
'(+
BBB! "AA%
[email protected] ' ' !=d''
:H" AA?% ' ) '
'* 4:9 [email protected] ' *""'' '@!
1% - ' *
) + '@
'
!-"###%,
" '* )
@9 C [email protected] 4:9 )
'* '@
!-"##%[email protected]",")4:9
'* '= '5!5L"##&%
=
4:9 9 *'" '
" ;65\:B ;65\:BB ) 4:9
');65\!6L9
''"##0%'3'"
-/; ) 4:9 ) >65 ! " ##$%" ! "##0%4:9
''
'*)
'
'965:V
'('!="##%565:!K"##&%"
6
6O;!68"##?%),4:9
6O;"
)4:9,)>;M!>';
('
)(% 4:9V&\
(
'
!M'+"##A%
&
*'
!T
+"#%/"
)
*
/65:4:9')
/65!:88
"#%
B*
'+
4:9B
H
+ ' +
' H
+
)+
H
) 9
-
''''"
4:9
' )
'+))
,
6 $)
*)')'6;9:
:
:
:(
7
(
69 !
% ) 6;9 !
%-)
S
''
[email protected] !6;9) % ( (
( 6;9 69 6/5!*
%,)
69
6;9!MK
"##%"!=
"##$%'
6;9" :
" :" - :
@" ' ' '
(
'
'
' '
!>" AA0% :
' :
H
S (
(
6;9
)')
S)*
?
6
+:
10#+
*/## 3
!"#$%&
'(#")*+,
") %$& #- *./- 0 , *
0
$3
""
+%&'#$
"%$&"(
!"#$
1 " #(23 0 , #.- 0 '4- -(
!-" ##?% : +
'' '+ ' !4
+ " AA0%" ') ' '
!BL2 " ##?% : ''):
[email protected]#'
''+:
@:
:
@
)'
/+"9*@
)[email protected]:9"
6/5
) 6;9 *
'@ 4:9 9*@[email protected]:9)
)+):,
!C
8'
"AA$%"!
3+%:6;9
'
- 9*@ , % '
) [email protected] ! ) L% % )
L
BC % (
) ) , !>' :(" ##0% - ' , ('
' " )
*' S
*
[email protected]"##%-H
'* ' [email protected]:9 9*@" 6;9:6;9*
M *-*
))
[email protected]*@
):'
!'"##%"!;
(
L"
##&%!
32%)
:+
9BC
)
(
@L6 C\!6(
(C\%"!-+
" ##?% 9;/4 !9
;/4 '
% '+ '@,+
)
[email protected]
!-+
"##?%
-:9 !
'
% (
' '
' '
/ *' )
' (')*
S*
!6
'"AA&%
B*&
8'''-:9
'
) " ) 4
' -' / '
' !K '" AA$% @ '@
$
6
+,
10#+
*/#
!
!"
#$%%"&'(
)*
&#
!
!"'$+&
!
!"' !
!"
, - -. - / #
"# -
4:9" 9*@ ) 5( 5 ) , ) -L& (
6 C \ (
-L& + ( -:9 ) & !=
2 " ##%" !O "
##&% !
5% - ' (
(
'' ;&#A" ;& &0 -:9 (
-:9 :
L * '
+ )
*
[email protected]' " ##&% -:9 ) 3 '
'
'
(
1,
)
(
[email protected]!4'"##%
6 6C3
)
M/65: (
))
+
'
'
" " ) M/65: (
) ) L '' *
'
!
7%
(
;(#&;(#&A
)
'*'M/65:!C
"AAA%;($&
''
)
-''
!9-c%))
@9C!77/C7/:C%)9C-
'
)
!;L"##%)
9-c'
+
'
)
)
9C-)
[email protected]; /6: !>
2
"##$%"!L
)"AAA%9C-)'9C
!
L % ( >@-$" (
+
'
!K"
##0%
+ ! '
( \ % '
9BC
!9
(
L%)');($&
'
)
'
!>
')"##%)
9BC)
'3'))
@L79C=)
!(
"##%"!5H
K"AAA%"!
"##?%'+),
))
4 !
*(%"!5L'"##%
(
;( )
'
)
'
(
S - [email protected]!'"##%;(A&
;@!;
0
6
+;
%60-
! !"#$%&!'
(
)() &!
$$*# + + ( + )+ )( &!$$,)
-
) &!$.#,$.#"
))
) /012/3$%/
3
4/)+.$$'
% ) ) ' '
'+ ) !'
" ##&% '" ) :" '+ ) !6) 6L"
##?% )
M/65: )
[email protected] !
L%" *[email protected]!Be
6;9)
%!e-
K"
##%"!;(
"##%
'
''
'
M/65: ' (
(
9-c *' ) ;(?AM/65:! 2
"AA$%B*
( ' > ! (" (
(%!B
"AA0%'
:
6;9-:
+
M/65:
M/65: <
4:9 '' '
*'
+)'
4:9)M/65:e*'4:9!K+
" AA%" ' ) +
4:9 !9 "
##$%"
4:9!W"##?%"!/)"
#%
:[email protected]+4:9!>8
"#%"
'
M/65:
)
4:94:9
'*
+ ) M/65: !9 " ##$% -
' 3 '
+ M/65: , ''+ !>
' P(" ##0% "
4:9 '''
(
# - M/65"
H
S
'
'
!/) " #% # - )
'
''[email protected]!
L%9(L=
M/65 + ' (
[email protected]" '
*
[email protected]
(
# -
*
9(L)'!/)"#%*
4:9
(
[email protected],
'H;(A$"'
(
;(#$ '' ' + !>8
" #%" ''
9(L - ) 4:9 ;(#$ , S '
) )
9(L7
#-
A
*
;. #$% 4:9+
*
)*
")
'
' +
4:9 , + '
* ) M/65?& 6 )
' 7 ! '@%" ' +7+ ! M/65?&% ! " ##$%" !9 " ##$+%
- '
" + )' +
' '@ +
'
M/65 " '
'
'
)'
B ' + '
' M/65 '
'
4:9?0&@ B ''
'+
)+)8'+
*
!+ '
% B " *
!' % !+
" #% ,
)
'
'
!KL"#%
)
''+(+
M/65?&4:9
LAA$',)
@;K99:''*
$M/65?&"+*'
+7+ 4:9 +
M/65 9 ''" '
+ '
( ' '
' ! 8 " ##?% - '3' '" , )
" ) H
+ ' (' ' )
'
!; " ##?%" !; " ##$%" !;
' " ##A% O '
&#
, ] '
( !H
'
',''+%'
,''+
'
) (
* + ) ' )
*
4:9! '"##?%
6
+
''+(+
4:9M/65: !6
"##&%-
'
'
)
'
' +
'
)
''
[email protected]% - '
, ( ' )
'
O+(0
'/60$"
'-'M/65?&"+
M/65?&4:9 !W " ##?% @ )*" '
')
+
' + - '
)
'
) M/65: 4:9" +
'
)
'
'
!W)"##%
<
(!60%+
, 49: " !48L"##%
)* :
, * -:[email protected]
(%,*'-'
<
4:9!;"##A%-
H
4:9 '' '"1,
*
'
--:
) 3 ) *' +
'
!CH"#%-
)
' ' + ' ' '
)
+ )
+ 4:9 ' '+ + '
))
+ '
+
49: ! 6+ 9
"
##?% ) , + *
" , +
M/65?& , 49:" 4:9M/65:
&
*
*
*
"
*
%
=+>
*
?
'<
50
<
*
=+0-7
*
%#>
6
-. 1 ! "
#$% ! &#%' ( %() &% (
*
)!'*!"
!
"+,-$&
./0112'
("'
+
M/65:
4:9
''
M/56
0 & $
''
*'
AA0 '
)
('
( = '
) [email protected]:% !-
' " AA0% - * M/ 9: ',*-'3'"
)
*@,'
+8
'S
* '' '
''+ *
4:9
'
!;'
"AAA% '/
*'*
)4:9 !6"##&%
*
'[email protected],%!;'
"AAA%@
'''+!9*@,9*@%"=
'''+!9*=,
9*=%" - ''+ 9*- 9* O '
)9*="
"
!"AA?%
>
*
''+)
#L"
'
'!
8%@*'4'*
)
' '"'++,
)8'
'''
) (
'' ' ' ' ) ' 9 B
!9*" '
" B% : ! : % '
) ' '(''
+!BL"B9;
;B6%(
)*=
)8('"
&
("')
(,''+
'
''*
[email protected]"##%
' ''+ '
) ' B
'+*'
(6***6
''
)
)'
(
'
'
' 9! *9*%)
?##
' ! ' - -% ) (
)
')+M
'--
-
'--
')
',)[email protected]!6;9
)
% !:
' " ###+% S ' +
)
:
6;9::
'M+*
:
6;9 ) 8 )+ '
(
+ !C:C 9*@ ::C 9*=% H
S ) 6/5 !6
* % '' [email protected]:9 9*@ 9P:
6/5 @:6 !L' :
6/5% 9*= !:
' "
###+%"!>"##%"!'"##%-
'(
'
' ' (
+ + )
' (
' ' ) * ! ) =LL"
AA%"!;
-
'
"##%-
'
(
' ( '' ;(
C
!;'
"AAA%
* ' 9*@ 9*= ) '(
'"
)9*=')*@
@ [email protected] " ##% !O " ##% / ) '
' - *' *@ * ' '[email protected]!4
"##%"*=
'(
'!;
" ##$% *@ ' '@ , 4:9 !W "
#% - ' ' * ''
9*@4:9"
' '!;L
'"##%
9*@ , '
' '
)
+
!;L '"##%
-'
*@!>"##A%*=
&
6
-+ " 1
0 !"#
$% &'
(')*$)# +,
--
& #--
&./+ )0
&+ )&
-1&2*%334$
*
! % ) +
)'[email protected]
"##%
1 / ' ) * [email protected]" @" @" @ % '* '
- BB
% 5B ' " '3' * )
) ' (
L !
% @" ;C
!L%,9*@
'@!K+
" ##% 8 )+ '? 8 )+ !;
(
L "
##+%'3'"M/65:3
* /" '?
' '* ;C9*@" )
'
'* 9*@
M/65:" '
, )" S +
'
'* ' !;
(
L " ##% -
' '('
'
)'
'?!-
"##A%
'3'" *@ ) M/65: ' (
M/65 !C " #% 9* ' ' '* ) 4:9 M/65: '/
'
)!%
/;>65!>
(6
25
%B
''
'(''
+!B9;%
* '' * /; *= '
'* , , '
)
/; &
, '!6
"##%-(
)+'()
*=+
/; '
'
' ! ) "
##%
/+=''+'/65:"
9*=
'/"
'
(
'*
S ! 28 " ##% )
9*= ''+
'3'
9 '
)
'
))
:
@9*=
)/+=
' '
) )
:
@ )
! 28 " ##0% O '
' /+=9*
'/!-88"##%
;:/ ! * '(
% @9 *' (' '' *' '
"'
'
;:/
''+ ' ''
+
@9 [email protected]^ @)
9
% ' ''+ '
B;@ !B''
(
+ )
'
%
' ) L
'' *' (L @9 '
B;@
*;:/-*)
'
'*) *@
'?
,'
L +
!;L"##?%
/"+
')*
* '
'' :
+
! %
!>h8 " #% -- ! % $&4;:! "##&%
'+
'
*
N ' '* ) '+*
"*'3'+)
) @ " ]
&&
)
+ '* ' +
' S ' * ' B" H ) '
'''+
'
S
'
&?
!
" "
!
6
--&
<
**3
#
# #
-8(
(
"
''+
&,#.
! )@L"###%"!5+"
##% - + '
'
,&#.+'')
''+ A$&" +
''
D)''+!>
O2" A$&% ' '
''+
'V
''+
!
%
'+
,''+
* '
+7 (
'
)*
''''+
+7 (
) *
'' ' ''+ - ''+ '
, # ' ''+ V" '
* \ '
0 , !
+% \
! 8"##%
*'
,
+
(
'
*''+
'
(
)
'' ) ''+
) (
+ * *
, ' , ''+ ' ''+ '
;
S ) ) " *
" " H
" 8('" '
)
!>"#%
&$
)#%+''+'
'
'
D 4
A$2
4
)
''+'"
'''
D
@/'"##&
-
)''+'
, ' )+ + ( (
' '
* ) ''
* '' '' , ''+)
''++
'
,A$"1*)* 4
'
'
D ! 4
" A$% !
)+% - '
+
'''
'
'
'+dL
+
''+
''
*'
! '+dL"A$&%@H
"
'
'* ' '
" '+ '
''+" '
''+
+
,'
'''
D
'' !/'" ##&% !
, )2% )
* )+ ''
''+ ! L
C'" AA% '+ 3 +8 ''' -
, ''+)
"(
' , ''+ )
E
''
''+! 8"A0#%"! [email protected]("A0%"!/"AA%
- ''+ 3 , * + , '' +
/
" * '' ' g '
''+<
<
('
! =L
)" ##$%" ! 4'" ##A%" !2
'
" ##%
' ''+)
'
'
'*
!6+"A0?%-
)
+ ''+ ('
!="##0%"!2"##?%"!
@L"##A%
&0
6
[email protected]&
5*)
**3
#3
$3
3 3 ! "#$%&%'
#
' '
' ''+
) +
''+ '
I ,*J !E;2
'
E%9
/'AA#
!9
/'" AA#% + -
'' '
'
* " ' '
V ''+ <
)
''+
' '* - '
3
' ' ' '
1 * ) ' +
*''+!/'"##%
'
" ''+ ''+ *' '+ ''+
'
''+*''
H
S ,
*
-
'
'
)'
,
'
!-+"##%@H
")
+ + '+
' ' - '* ) ''+
'*
S)
+
;
) )' '
)
''+ H
'' '
',''+'S
'', "
(
''+ '+ '* ''+ + ) 3 )+
* ' ' '
('+'
+
!2 " ##?%" !=" ##0%" !
@L" ##A% @" (' ( '
)' !
* +9/% % % % '
)')
%
,''+!2"##?%"
!
@L" ##A% '+ '
)' )
&A
6
-A&
5
*
**
%#3
!" #$$%
'
'' '
''+ / )*" +
' '
''+
(
(
@[email protected]%"
''+ (
( / " +
'
' '''+'
'
!:4% )
* ! ' =
'" AA&%" !C8 " AA$%" ! ' " ##%
e )" ( +
' '
''[email protected]'+
' '
+))
)
!=
'"A0A%
''+
)
('
''
'
'
'
"'
F$&B**6M**6M**;0$!''
" AA% N [email protected] '' 6***6 ' ' '*' * MK
(
')
)
+'! "##%"!=
2"##&%!
0%*6
)
) " " '+ M H - '+
' ( E
+
] '' '' !
>"AA0%
''+ )
M K" , , '
(
*'
'
) S +
' B * (
"+'
'+
(
+(-V>
!
( K" AA0% +
!-% + (
'
,
"
'' ) ' (
) !W)
" AAA% " (
'
! "##%
?#
9 " ' ',
')
''+ ' * + !j&
. )'% ) +
9*'"! %
)
[email protected]' " ##% ' ''
!4%!-
'"###%"!%"'!e%"
'!/%
((
,*
!P
" ##%" !6L
2L " ##%" !P
" ###% ''
)','
'
+
(
+
!2
"##%
) '
6***6 )
" '
'* , H
' ''+ !- /'"##%"! "##%B)''(
@ ' ' '
''+)
.'
)
! " ###% B ' '
''+ ' '
)
'
' [email protected] ="AA0%"!:/'"###%"!"##%'
6***6'
* ( ' '+' - '' ' '
M K (
'3'" '
'*** '" '' '
''+" ' , '' (
!6%"[email protected]%"! %
!;%
6***6
3
''
'+ 3 ' S ' )
'
'
'
, * ' ' !
?
)
% ! /'" ##%" !
" ##%"
!(L"##%
'
6***6 '
( E( 8 ' , '
' )
!C'"##&%B*'EE8
)
' '
'' +
'
)3
!%" !B% ) !M% ! " AA%" !: "
##%
/" '
' '' - '
(
**
**; ***
**; '
!2
" ##% -" '
, " ' )
' H +'+
@" '
''+ ( ' '('
* 4 & #% #
'
' ''+ ) / " '
' + , '
- '
'H '''+
* #
6=
, ) (
L !:;C% ' &0 ''+
# ' O ' ) :;C
'
,
'
' '
?
''+
'
'
'''+!5"##A%'
'
':;C'*
)
(
(
' + ,
)
':;C
''('
''+'
'
4'/+=8
!='"
A0?% B '' '
' ) !M% ' !/% '
''+ - '
)
)
) '
+ (
' !=' K+" A00%" ! ' " AA?%
O )
'
+
'
'
, ,
)
)'!=)"##%"
'
' ''+ ' '
*
' H*''+ , ''+
!"#%
'3''"8'"
''+!/+="/+="/+="/+=%
'
'!
"##%
'
! " ##% ''+ ' '
'* ) * '
6***6 ' ''+ /+= /+= !5' "
##%" !/ " ##A%" !-(' " ##% '
) ' ''+ !;% /+= :4!=
)"##0%
'
'/+=/+='
H" )' '
6***6 !'
( 8% + '
'
;*** ***6
(
-
' '
'
'+ ' '
) /+= ' '
'
+'
'
'
!6+"##%"!)"##%
=
:;C ( " /@"
"'
'
S
'
''+ '
' !=
) " ##0+% - '
( 8 @***6***6 ?
4' /@ , '
***6**@***M**'
'
'
!=
)"##%
' ''+ 565: '
' ' !K+ " AA?%" !4
5" AA?%"
!B2'
" ##&% '
' ''+ )
' , ) /
" '
' ; 565: , ' (
!
)
'
1% !K " ##&%" 565: (
' =
)
" ' , '
' ' ' ' 1"
!98( " AA?%" '
' ; 56: ) '' G
!=
) " AA?% (
' 6
8
!("AA&%"!K+
"AA$%565:"
''
4"'
;
)
)
)
'
!="##%
:;C ( ' ''+ '
'
S ; '
'*/"!-'"
AA%" !6 " AAA%" ' 965: ! " ##&%"
!5'-
L"##&%"!;+ "##A%"!"##%"!
6
"#%"!9"#%":/;!CH"##?%"!-
'+
=L'
" ##0%" !=H " #% M/65: ' ; )
'
'
!
='>
"##%
* !>".!?
:-96 ' ''+
) 0## ''+ B ( ) $ '
''+ '
$ , ' ' +
* ' ''+ '
4' $ ) -' B
) 3 ) ' " " '
?
"'
!'""
"
%"
'
*
!
%" '
L" !
'
(
% *
' '
+ ) '* 6'!6V"6\6c%-
)
'*
6*"
6V
'*
69'
6;9"
')''
:-96 ) ' ' ' '* 3
* ' ' '
''+ ( H
S 9
*'" ' ''+ @@ +
'
' , '
!;) "
##&% \ * '
'
'''+
; ;& !> " #% ' ''+ :-96
'+*'
6***6"'
' ' '
6***6 + ,
'
'
'
8);:-96
!)
" ##% -" * ! ( '
' ' ' '
'% '' *' !C
"##?%"
'!6
"##%"!6
"##&%"!6
"##0%"
'&>;-!"
##0% @" ' ; '* '*
'
+
)'*
:-96
*) '*'<
+'
'' " '
!>(" ##% ' ) '
*" ' ''+ ) ?&
(
)
'
')
V
\ B * 0 V )
? \ )
'
'+
+
)
O
'''+!V"VBB+"
V" \" \ \$% '
' ' ''3'
'
'! /'"##+%-
' ''+ '
'*
'
'
''/"
' , )
'
' )
" '+ ' ''+
' ' '
+ !
"##?%
*
' )
!P " ##$%" ! "
##A%
'
' ''+ ' '''(!""%!2L8"##$%"
'(9!
'
';'+'
-
;
" !9
L
2L " ##$% !99% '( ' ; !4 +"
##%'3'"'
';/
4
!>+ " AAA%" !T
L " ##?% /" )* '
'
' ; (
+) !:
( "
##%" !=
2 " ##%" !=
2 =" ##?%" '* [email protected]:/ '
)*
(
)''+!58"
##%
** =
(
D" /
:" +
'
'
' '
'
D ' ] '
'
* ; '
'
!-
"##%"!C+8L("##%e"
??
'
'
P!:"
##%' ' ''
''''
!/+5'"##$%
9:: 3 '' *' (
L'
'''+
3
!6-)"##?%,
"
@99!'(
%"
= ! H
L8" ##A%" ; ! "
##%"@9>
'*c
;
L
!6
("#%
'
';
'
'*
'
0 .
#
$% "''"
''+ )
, [email protected]
K" ##% - ' +
'''+
' '
+ AA$ ('
( ;" !
" AA$% - '
0 ''+ ) " ' !V\% ) ] ) - !- % ' '
!- kk% '" !-lm - lc% '
'*
;-: ' )
('
( ; ''
' ''+ V ) '+
+
+V
-ml!
"AA#%O''
'''+
;-:V"+')
('
(;
'''
L ' " '
))
''
'
' ('
( ; '' H)" )*'+(
'-
?$
''
' ('
( ; !6n " ###% - '
) ' !' '
% ' '
' , ' ' '' ) ( " ' , !6+ " ##&% '
(
+ ''
[email protected]'
"##?%
S
'''+
'
'*
)
))''+!+("AA%"!-8
"##$%"!C'
" ##A%" !
" #% - )* '
' +
' ''+ '3 ) !=
" ##$%"
!9
"##%"!=
8"#%"! "#%
O
'
'*
'' ! :" ' : % - ' ''+ * + , ) '
* !( ' +
% " ' ''+ + '
''+ : + + , +
!9
+" #% *
" ''+ ) '
''+ @; !>' %
'
+ ' ? + +
'
'
!"#%
'
) )* '
7'
'
>+T)*
'
'
'
+ + ' ''+ ' !T " ##$% - ) ->@9 !
' ''+ % + ' ' ' ->@9 '
'VBB+\V)\B
')
'''++'
'
VBB+V)
- ) ) '* +" VBB+\ '' ?0
->@9 ' +
'''
(
->@9VBB+
) VBB+\ ' +
!-
" ##0%" !6(L " ##A% 9 ''" '
'
''+
+
'\+
+VBB+\
)
! "#%
1 ;%
+
) ' (''
'''+
+
' )* +
/65: /+= )*
'''+
' ' (
+ , !=
"##%-
*(
F @ *' /65: CM ) *' /+= * " ,''++'
(
+ )
H
'' )
/:C ' ' ''+ ' ' ; /65: /+= -> ' '
)+!=
"##&%
@ )*" +
, '
3-
'';
)
+,
'
' 4:9" ' '+ +
, * ) + ' ' + , ' ) 4:9 1 , '
'* *' M/65: != " ##%" != " ##% * !9d" ##% '
( 6***6 '
?A
6
-B&
)
5)
='>
**
*
**
3
''+4:9''+*
+(+!
(';
*%"5:/;!))
;
(,
'% )
( '
4:9 + '
' ' ''+ !:
"
##0% ( '' ' ''+ 4:9!;94:9%++
",+
!# %"
*
*
- *'4:9
9*@
, '@-;94:9+
'
'
4:9
('
'@
M/65
4:9
),&#.
B,
')
+
( '' ' ; , +
@ ," 3 ( -
' S 4:9 " '
" )* ) ' '" '
+ ' ) , *
4:9 '
'
H , )* @ '
" ' )
;+
''*!
1%
$#
+HF
-
''
)
)
"
'''+
H'
'
,
S )* '
+
) '
'
'''+4:9'
!:
"
##0% - )* ' +
, ' (
+
+ ' ''+ 4:9 '
+
O +
, H ' '' + ' !4 " ##%
*"'
)''
)
)
'
;94:9 ' '
'
*' +H , ' ;94:9 ' ''+
+
'
+H")3
"
,
) " *@ -
'')4:9
'@B)
''
(6***6
' (
'
'
''+
$
,:+,
$
) ''+
'''
4:9!;94:9%'
+
4:9'
'
*' *
;94:9 )
' ' '
'' +
+
4:95'" '
)
*
)F9*@
$
9BF
-
+
,'+
'''+
'
$
! * 0 ! * 6
-:&
8 !"#$% !$"#$&!
"#$%!$"#$
'()*+$,&-&%.
6
-,&
*
**
C)
*5
=#'>
"#6&&&$#
# 9 &
@#A
''
++'
''+4:9
+H:
+:)
=
(
-!:
"##0%@
)*" 3 !;94:9%
'' , +
+
'
-
''
)
)
"
*'
'
''
4:9
+
',
'
" '
'
-"+##)
'
;94:9
) )
' '
7
''
'-'H
'
"H
)
))
+")(
'",'
' H )
, ) ' !>OM/-% ' '" ('
'
BM
'+
+565/65
S"
'
'*
'
+
'+,
? ) '' $&## !
3% H
;94:9 , #$ )' '
'''
'
)
'+
??.
!j#"#&%
'++!$#.%!j##&%O
)
) ' ;94:9 ( '
6***6
')"'
*'
$&
! * 1 = D > 6
-;&
#'
!"#$%&
03.4#'()*!+-./$012$
"
!#'()*! " +,#'()*!+-./$012$
"
03
.5.6
789$:;<
#
@)
;94:9" H''
+
'
''+
D
'+(
! [email protected]% - '
' + '
' +)
)* ,
+'
;94:9
''+ 4:9 ) , ## . 8 ' N ) ) >
H
''
'+(
) '
+
N H
, $o- ) )
' '+(
H
' !
5% @ ' H
" '+(
)
'"
+
) , $o- @ H
+
'" ''+
D')B
+
)* )
'" H
) )
+,F#_
9= "M/65,#_7'"
;94:9#$ ";94:9'#$ '+
@+
8
)
,
)*
'H
'
''
S"
+)
(
'
)* '+ )* ' !
7% / M/65 !#"7'%" +) ' ) '+ )* ' i?$ . !U% S9
;94:9'3
M/65!0.7M/65"j#"#&%!U0%
';9
4:9''M/65!AA.%!U#%'+
'
;94:9 + + M/65
$?
Oncogene (2010) 29, 2381–2392
& 2010 Macmillan Publishers Limited All rights reserved 0950-9232/10 $32.00
www.nature.com/onc
ORIGINAL ARTICLE
Peptide-based interference of the transmembrane domain of neuropilin-1
inhibits glioma growth in vivo
C Nasarre1, M Roth1, L Jacob1, L Roth1, E Koncina1, A Thien1, G Labourdette1, P Poulet2,
P Hubert3, G Crémel1, G Roussel1, D Aunis1 and D Bagnard1
1
INSERM U575, Physiopathologie du Système Nerveux, Strasbourg, France; 2Laboratoire de Neuroimagerie et Neurosciences
Cognitives, Institut de Physique Biologique, Strasbourg, France and 3LISM, CNRS UPR 9027, Marseille, France
Angiogenesis in glioblastoma is largely dependent on
vascular endothelial growth factor (VEGF) signalling.
Consistently, the VEGF coreceptor NRP1 promotes
angiogenesis and tumour growth in gliomas. Here, we
provide data showing that an innovative peptidic tool
targeting the transmembrane domain of NRP1 efficiently
blocks rat and human glioma growth in vivo. We show
both in vivo and in vitro that the antitumour effect results
from the anti-proliferative, anti-migratory and antiangiogenic properties of the compound. The proposed
NRP1 antagonizing peptide is therefore a promising novel
class of anti-angiogenic drugs that might prolong glioma
patient survival. Our results finally show for the first time
that the transmembrane domain of important signalling
receptors can be antagonized in vivo thereby providing a
new avenue towards the development of atypical antagonists with strong therapeutic potential.
Oncogene (2010) 29, 2381–2392; doi:10.1038/onc.2010.9;
published online 8 February 2010
Keywords: neuropilin; glioma; angiogenesis; peptide;
tumour growth
Introduction
Glioblastoma multiform (glioma, grade IV astrocytoma) is one of the most severe and frequent brain
tumours. The median survival time of patients is not
exceeding 15 months due to the lack of efficient
treatments. The highly invasive phenotype of tumour
cells is associated to formation of new blood vessels
favouring tumour growth (Jain et al., 2007). Recent
preclinical and clinical data suggest that anti-angiogenic
strategies may be useful to fight glioma development
(Jain et al., 2006; Xu et al., 2009). To address the need of
new strategies to interfere with glioma growth by
inhibition of neovascularization, we tested a peptidebased inhibition of neuropilin-1 (NRP1). This transCorrespondence: Dr D Bagnard, INSERM U682, De l’homéostasie
tissulaire au cancer et à l’inflammation, 3 Avenue Molière, Strasbourg
67200, France.
E-mail: [email protected]
Received 24 August 2009; revised 19 December 2009; accepted 3 January
2010; published online 8 February 2010
membrane protein, initially described for its role during
nervous system development (Bagri and TessierLavigne, 2002), is a positive modulator of vascular
endothelial growth factor receptor 2 (VEGFR2) and is
thereby a crucial fine-tuning element of angiogenesis
(Jocic and Staton, 1993; Hong et al., 2007). Moreover,
consistent with several descriptions of its importance in
tumourigenesis and tumour progression (GuttmannRaviv et al., 2006), NRP1 promotes human glioma
progression (Hu et al., 2007). Hence, recent data
show that VEGF blockade upregulates inflammatory
pathways and NRP1, thereby presenting NRP1 as
a potential target for improving anti-VEGF therapy
(Xu et al., 2009). Our previous work showed that the
transmembrane domain of NRP1 contains a GxxxG
dimerizing motif required to trigger efficient signalling
(Roth et al., 2008). Genetic or peptide-based inhibition
of the transmembrane domain appeared sufficient to
block NRP1 oligomerization and subsequent biological
functions. Here, we found in models of orthotopic
and heterotopic brain tumours that synthetic peptides
targeting the transmembrane domain of NRP1 (pTMNRP1) inhibit rat and human glioma growth in vivo.
This antitumour effect relates to the inhibition of
VEGF-dependent cell migration and cell proliferation,
and to anti-angiogenic effect of the peptide as shown
in situ by the reduction of microvessels density and
neoangiogenesis (Taguchi et al., 2004; Uzzan et al.,
2004) both in rat and in human glioma. We confirmed
this action mechanism by using an in vitro and in vivo
angiogenesis assay. Overall, our data not only show that
the use of peptides antagonizing NRP1 is a very potent
therapeutic strategy to treat glioma, but also exemplify
that the transmembrane domain of proteins is an
outstanding target to design innovative drugs.
Results
pTM-NRP1 is an anti-angiogenic agent
Considering the important function of NRP1 in angiogenesis, we evaluated both in vitro and in vivo how
addition of pTM-NRP1 would interfere with blood
vessel formation. This hypothesis was supported by our
previous results showing that pTM-NRP1 reduced
VEGF165 binding to NRP1 (Roth et al., 2008). First,
Inhibition of glioma growth using neuroplin-1 peptide
C Nasarre et al
2382
4
ns
8000
ns
6000
4000
2000
ut
P1
m
P1
R
R
-N
3
2
ns
ns
+
-
+
ns
1
0
VEGF pTM-NRP1 pTM-NRP1mut -
+
-
+
+
-
+
+
+p
TM
-N
M
+p
T
co
n
tr
ol
0
*
*
Proliferative
index (24h)
Number of Cells
(6h incubation)
10000
cont
+VEGF
+VEGF +pTM-NRP1
VEGF +pTM-NRP1mut
Cell aggregates with
migration (%)
100
80
60
40
20
0
VEGF
pTM-NRP1
-
+
-
+
+
+
-
pTM-NRP1mut
-
-
-
+
Figure 1 Inhibition of human umbilical vein endothelial cells (HUVEC) proliferation and migration. MTT assay performed at 6 h
incubation revealed no acute toxicity of the TM peptides (a). Vascular endothelial growth factor 165 (VEGF165)-induced HUVEC was
blocked by pTM-NRP1 but not by pTM-NRP1mut (b). VEGF165-induced migration of HUVEC cells from microaggregates grown in
chicken plasma was blocked by pTM-NRP1 but not by pTM-NRP1mut (c).
we verified that pTM-NRP1 had no acute toxic effect on
human umbilical vein endothelial cells (HUVEC cells;
PromoCell GmbH, Heidelberg, Germany) grown 6 h in
the presence of the peptides as seen in Figure 1a.
Second, we monitored cell proliferation using MTT
assay after 24 h incubation. This approach revealed that
pTM-NRP1 or pTM-NRP1mut (an inactive control
peptide in which the three glycines of the dimerizing
motif have been replaced by three valines) (Roth et al.,
2008) had no effect on HUVEC cells proliferation in
control culture conditions (low serum, low VEGF).
However, pTM-NRP1 but not pTM-NRP1mut prevented
VEGF-induced HUVEC cells proliferation (Figure 1b).
We next examined the migration of HUVEC cells grown
in a 3D matrix composed of chicken plasma coagulated
with thrombin. This substrate allowed cells to migrate
from microaggregates of HUVEC cells incubated with
or without VEGF and peptides. As seen in Figure 1c,
HUVEC cells formed chains of migrating cells on
addition of 100 ng/ml VEGF165. Interestingly, this
VEGF165-induced migration was abolished in cells
treated with pTM-NRP1 but not in the case of pTMNRP1mut treatment. Consistently, the anti-angiogenic
effect of pTM-NRP1 was revealed in the matrigel assay
Oncogene
(Matrigel; Millipore, Molsheim, France) favouring tube
formation. In our hands, we observed a dense network
of endothelial cells forming tube-like structures within
4–6 h (Figure 2). Interestingly, the addition of pTMNRP1 inhibited tube formation. The use of various
concentrations of the peptide revealed a significant effect
from 10 8 M reaching a maximal inhibition with 10 7 M
(data not shown). Quantitative analysis of this antiangiogenic effect performed by counting number of
tubes or network complexity (number of branch points
or intersections) showed a threefold reduction of
angiogenesis in the presence of pTM-NRP1. In all
cases, pTM-NRP1mut had no effect on tube formation
(see Figure 2). Hence, we confirmed the anti-angiogenic
effect of pTM-NRP1 using the in vivo CAM (chick
chorioallantoic membrane) assay. In this case, the
addition of 20 mg/ml VEGF165 induced blood vessels
formation and sprouting. Strikingly, VEGF165-induced
blood vessels formation was abolished in the presence of
pTM-NRP1 but not in the case of pTM-NRP1mut
treatment (Figure 3). Altogether, these results showed
that pTM-NRP1 inhibits VEGF-induced endothelial
cells proliferation and migration and subsequent proangiogenic effects.
Inhibition of glioma growth using neuroplin-1 peptide
C Nasarre et al
ns
40
30
20
*
10
R
P1
m
ut
P1
l
0
+pTM-NRP1mut
Number of intersections
+p
T
M
+p
-N
TM
R
-N
co
n
+pTM-NRP1
50
tr
o
control
Number of tube-like structures
2383
150
ns
100
50
*
ut
m
R
P1
-N
+p
TM
-N
M
+p
T
co
nt
ro
l
R
P1
0
Figure 2 pTM-NRP1 blocks in vitro angiogenesis. Human umbilical vein endothelial cells (HUVEC) were grown for 4–6 h on
matrigel to allow tube-like structure formation in the presence or not of TM peptide. Quantification of angiogenesis was performed by
counting number of tube-like structures or number of intersections. Phase-contrast images obtained using a macroscope (Leica,
Nanterre, France). Scale bar ¼ 100 mm. *Po0.05.
pTM-NRP1 stably integrates tumour cell membranes and
blocks NRP1 function
We next evaluated how pTM-NRP1 could be used as a
therapeutic treatment in cancer. First, we focused on the
rat glioma model C6 cell line (American Type Culture
Collection (ATCC, Manassas, VA, USA) CCL-107)
recapitulating characteristic features of human glioma
(Wang et al., 2001; Grobben et al., 2002). We verified
that our clone of C6 cells expressed significant levels of
NRP1 using both RT–PCR and immunocytochemistry
(Figure 4a). Moreover, we determined that pTM-NRP1
integrates the membrane of C6 cells within 1 h using
a biotinylated version of the peptide revealed with
rhodamine-conjugated streptavidin (Figure 4b). These
control experiments also showed that significant amount
of pTM-NRP1 is still detectable at the membrane after
24 h incubation. Long-term analysis of pTM-NRP1
membrane incorporation using confocal microscopy
revealed cell-surface clearance of peptide after 96 h
(data not shown). Consistent with our previous description of the action mechanism of the peptide (Roth et al.,
2008), we found in C6 cells that pTM-NRP1 altered
oligomerization of NRP1 on addition of Sema3A
(Figure 5a), a semaphorin involved in glioma migration
(Nasarre et al., 2009) and shown to promote glioma
dispersal through an autocrine mechanism (Bagci et al.,
2009). Moreover, although not inducing acute toxicity
in C6 cells (see Figure 5b), the addition of pTM-NPR1
induced a significant reduction of cell proliferation
( 32%, Po0.05, Figure 5c). Interestingly, the reduction
of the proliferative capacity of C6 cells when blocking
the transmembrane domain of NRP1 was confirmed
in flow cytometry analysis performed with C6 cells
stably expressing a dominant-negative form of NRP1
(Roth et al., 2008) that also caused a significant
reduction ( 26.5%, Po0.05) of C6 cells proliferation
(see Supplementary Figure 2). Hence, similar to what we
obtained with HUVEC cells, we found that VEGF165induced C6 migration was abolished by pTM-NRP1
but not by pTM-NRP1mut. Indeed, we rarely observed
cells exiting microaggregate in the absence of VEGF
treatment (o3% of the aggregates over a total of
182 cases) after 24 h culture. The observed migrating
chains in the presence of VEGF (in 93% of tumour
aggregates, n ¼ 180) mimicked what is frequently
observed for invasive cells or migrating progenitors
in the brain (Garcia-Verdugo et al., 1998). The addition
of pTM-NRP1 in the culture medium suppressed
VEGF-dependent C6 cells migration (2% of aggregates
presenting chains of migration, n ¼ 161, Figure 4c)
Oncogene
Inhibition of glioma growth using neuroplin-1 peptide
C Nasarre et al
2384
1)
2)
3)
Number of blood vessels (%)
300
4)
*
*
200
ns
100
-N
-N
R
P1
m
ut
R
P1
F
EG
F+
EG
4)
V
3)
VE
G
pT
F+
M
pT
M
2)
V
1)
P
B
S
0
Figure 3 pTM-NRP1 blocks in vivo angiogenesis. The CAM (chick chorioallantoic membrane) assay served to evaluate antiangiogenic properties of pTM-NRP1 in vivo. Microphotographs and corresponding camera lucida drawing were obtained after 24 h
incubation with phosphate-buffered saline (PBS) (1), VEGF165 (2), VEGF165 þ pTM-NRP1 (3) or VEGF165 þ pTM-NRP1mut (4).
The number of blood vessel in the region incubated with different solutions served to quantify the angiogenic effects. *Po0.05.
whereas pTM-NPR1mut did not prevent VEGF-induced
chain formation (96% of aggregates presenting chains of
migration, n ¼ 179, Figure 5d).
Thus, pTM-NRP1 is able to block Sema3A- and
VEGF-related NRP1 functions in C6 cells. This resulted
in decreased proliferation and migration of the C6
tumour cells.
pTM-NRP1 prevents glioma growth in vivo
We further explored the therapeutic potential of pTMNRP1 in a model of orthotopic brain tumour (Grobben
et al., 2002). We stained C6 cells with PKH26 (Sigma,
Saint Quentin Fallavier, France) to easily determine
tumour extent and cell dissemination by fluorescent
examination of brain slices (see Supplementary Figure
1). We standardized our conditions to have comparable
tumours 8 days after injections. For treatments, cells
Oncogene
were incubated with the active peptides (pTM-NRP1
10 8 M) before tumour cell transplantation for at least 2 h
on ice in culture medium. We transplanted 106 cells per
animal using a stereotaxic frame to implant the tumour
cells in the striatum. In control conditions, we obtained
large tumours often giving rise to secondary tumours
developing at a distance of the injection site. This shows
the highly invasive behaviour of these tumour cells
often seen migrating along the corpus callosum (see
Supplementary Figure 1; Grobben et al., 2002). We used
magnetic resonance imaging (MRI) to analyze tumour
progression in control (three cases) and pTM-NRP1
(three cases) treated animals. As seen in Figure 6a, after
8 days, the growth of pTM-NRP1-treated C6 cells was
dramatically reduced compared to control cells being
almost not detectable in certain cases with MRI. To
confirm these data, we extended the analysis to increase
the number of cases and we included an additional
Inhibition of glioma growth using neuroplin-1 peptide
C Nasarre et al
2385
no RT
Cos
Cos-NPR1
C6
GAPDH
NRP1
No peptide
+1h
+4h
+24h
Figure 4 Expression of neuropilin-1 (NRP1) in C6 cells and incorporation of pTM-NRP1. (a) NRP1 expression in C6 cells was
confirmed by either RT–PCR or immunocytochemistry. The specificity of the immunostaining is shown with COS cells (not expressing
NRP1, negative control) and COS-NRP1 (transfected COS stably expressing NRP1, positive control). (b) Time-lapse sequence
showing the incorporation of a biotinylated version of pTM-NRP1 peptide revealed with Streptavidin-Cy3. Note the persistence of
peptide in the membrane after 24 h incubation.
control group of animals receiving cells preincubated
with the mutated inactive version of NRP1 peptide
(pTM-NRP1mut 10 8 M). The histological analysis of the
brains confirmed that blocking NRP1 with pTM-NRP1
(12 cases) inhibits tumour growth (up to 80%) in a
remarkably reproducible manner (12 out of 12 cases). In
control experiments (no treatment of the cells, 12 cases
or incubation with pTM-NRP1mut, 7 cases), C6 cells
developed large tumours with secondary implantations
often lying at the ventricle border (see Figure 6b). This
reduction of tumour growth can be related to the
inhibition of cell proliferation and cell migration
observed in vitro.
Local and intraperitoneal administration of pTM-NRP1
inhibits glioma growth in vivo
At this point, our data supported the use of pTM-NRP1
as a novel pharmacological agent to treat glioma.
However, because tumour cells were preincubated with
the peptide before intracranial transplantations, we had
to verify the therapeutic potential in predeveloped
tumours. We therefore decided to perform local injections of the peptides directly in the tumour surrounding.
Unfortunately, we failed to perform this experiment in
tumours implanted into the brain due to numerous
animal deaths on additional injections and poor
diffusion of the peptide from the injection point. Thus,
we decided to use a heterotopic brain tumour model
consisting in the graft of the tumour cells in the flank of
athymic nude mice (Kelland, 2004). This allowed us to
perform multiple injections of the peptide around
developing tumours and allowed the use of a human
glioma cell line. In fact, the transmembrane domain of
NRP1 is 100% conserved in mouse, rat or human. This,
besides pointing out the importance of this domain from
a phylogenic point of view, allowed us to use the same
peptidic tool, targeting both the human tumour cells
and the host blood vessels. We choose the glioma cell
line U373MG expressing high level of NRP1 (Hu et al.,
2007) (data not shown). To this end, we transplanted
U373MG cells in mice and checked for tumour
apparition after few days. We usually obtained visible
tumours under the skin of animals within 4 days. At
this point, we randomized mice in two groups receiving subcutaneous injections of phosphate-buffered
saline (PBS) or 10 7 M pTM-NRP1 in PBS for a period
of 10 days. To further characterize evolution of
individual tumours, we estimated tumour volume in
blind condition every day (volume ¼ (a2 b)/2, aob)
(Hu et al., 2007) using a calliper on subcutaneous
administration of first dose of treatments (PBS or 10 7 M
pTM-NRP1). As depicted in Figure 7a, the growth
rate (final volume/initial volume) of U373MG tumours
reached 7.9-folds in control conditions while not
exceeding 3.6-folds in animals receiving daily local
administration of pTM-NRP1 (Figure 7a). Consistently,
the determination of final tumour weight confirmed
Oncogene
Inhibition of glioma growth using neuroplin-1 peptide
C Nasarre et al
Number of cells (6h incubation)
2386
NRP1 (%)
60
*
**
30
0
Proliferatve index (24h)
monomer
3
+Sema3A
+pTM-NRP1mut
6000
4000
2000
0
cont
10-8M
10-7M
10-6M
10-6M
oligomer
dimer
+pTM-NRP1
2
+pTM-NRP1mut
*
1
0
cont
+pTM-NRP1
8000
+ Sema3A
+ pTM-NRP1
10
-6M
10-6M
Cell aggregates with migration (%)
control
10000
120
100
80
60
40
20
0
VEGF
pTM-NRP1
-
+
-
+
+
+
-
pTM-NRP1mut
-
-
-
+
Figure 5 Functional effects of pTM-NRP1 on C6 glioma cells. (a) Sucrose gradient analysis of neuropilin-1 (NRP1)
oligomerization(11). As previously shown for other cell types, pTM-NRP1 prevents NRP1 oligomerization on ligand binding
(Sema3A). (*Po0.05, three independent experiments). (b) MTT assay served to determine the lack of cell toxicity of the peptide
(number of cells obtained in six different culture wells per condition from three independent experiments). (c) The MTT assay also
served to determine the proliferative index (number of cells at 24 h/number of cells at 6 h) of the cells after 24 h incubation with peptides
(six different culture wells per condition from three independent experiments). (d) C6 cells migration assay. Microaggregates of C6 cells
are grown in a 3D matrix. Addition of pTM-NRP1 blocks VEGF165-induced cell migration.
the significant reduction of tumour growth (1.7±1.1 g in
control n ¼ 19 versus 0.9±0.7 g in pTM-NRP1-receiving
group n ¼ 20, Po0.001, Figure 7b). Control experiments conducted with C6 wild-type cells and C6
cells stably expressing a full-length NRP1 mutated in
its transmembrane domain also showed a reduction of
glioma growth when inhibiting the transmembrane
domain of NRP1 (see Supplementary Figure 3). Strikingly, we observed during U373 tumour resection a
dramatic reduction of tumour perfusion in treated
animals (see Figure 7c). Although numerous and large
blood vessels colonized the tumours in control conditions, rare and small vessels were seen in pTM-NRP1treated animals. To further analyze the reduction of
blood vessels formation in treated tumours, we performed histological analysis of tumour samples
(from smallest, medium and largest tumours of the
two groups). Quantification of blood vessels using
isolectin-B4 revealed a sixfold reduction of blood vessels
number in animals receiving pTM-NRP1 (16.4±6.5
vessel per mm2 in control tumours versus 2.6±1.5
vessels per mm2 in pTM-NRP1-treated tumours,
Po0.05). Similar results were obtained using CD31
(endothelial cells) or CD34 (neoangiogenesis) (Goldbrunner et al., 2000) as blood vessel markers
(Figure 8). Thus, the antitumour effect of pTM-NRP1
in human glioma can also be correlated to antiangiogenic effect.
Oncogene
Hence, we decided to test whether intraperitoneal (IP)
injection of pTM-NRP1 might induce similar therapeutic effect. As a first step, we monitored the distribution
of a rhodamine-conjugated peptide (Rhod-pTM-NRP1)
using a live in vivo imaging system (Berthold, Thoiry,
France). As seen in Figure 9a, we observed a large
distribution of the peptide 15 min after injection. The
tumour mass was clearly stained whereas low level of
staining could be monitored in the brain. Interestingly,
the histological examination of tumours from animals
receiving IP injections of Rhod-pTM-NRP1 confirmed
the distribution of the peptide in the tumour mass. A
close examination showed staining of intratumour blood
vessels accompanied by diffusion of the peptide in the
surrounding tissue (Figure 9b). This result therefore
suggested that IP treatment could be used in the model
of human glioma xenografts previously used for local
administration of the peptide. Indeed, as depicted in
Figure 9c, daily IP injections induced a 50% reduction
of the tumour mass comparable to the effect obtained
with local injection.
Discussion
As a conclusion, our data show that antagonizing the
transmembrane domain of NRP1 is an outstanding
strategy to inhibit tumour growth in vivo. In the case of
Inhibition of glioma growth using neuroplin-1 peptide
C Nasarre et al
2387
Control
+pTM-NRP1
Ctx
CC
LV Hp
Control
Str
+ pTM-NRP1
+ pTM-NRP1mut
T
T
Figure 6 pTM-NRP1 inhibits tumour development in vivo. (a) 3D reconstruction of tumour bulks obtained from magnetic resonance
imaging (MRI; 4.7 T) pictures of control (case 1 out of 3) and pTM-NRP1-treated animals (case 1 out of 3). Note the reduction of the
tumour volume in case of the treated animals. (b) Histological analysis of brains. Tumour cells were stained before transplantation with
a red fluorescent marker (PKH26). Note the reduction of tumour size and the lack of secondary tumours in pTM-NRP1-treated
animals. Sagittal view, images were taken using a macroscope (Leica) equipped with fluorescence light (left, bright field; middle, red
fluorescence; right, overlay). (T, tumour bulk; Ctx, cortex; LV, lateral ventricle; Str, striatum; CC, corpus callosum; Hp, hippocampus).
glioma, the observed reduction of tumour progression
relates to the inhibition of VEGF-related proliferative
and migratory promoting effects and defaults of
neoangiogenesis. We have shown the anti-angiogenic
property of pTM-NRP1 in two different models
(matrigel assay and CAM assay). In all cases, we show
that lack of tube formation or vessel formation and
sprouting is not due to acute toxicity but due to the
inhibition of endothelial cells proliferation and migration in response to VEGF. Moreover, pTM-NRP1
directly induces reduction of tumour cell proliferation
and migration. These inhibitions can be correlated to the
interference of NRP1 oligomerization as previously
described (Roth et al., 2008). Interestingly, the addition
of pTM-NRP1 before tumour cells transplantation
reduced the growth capacity of glioma into the brain.
This is reflected by a strong reduction of the tumour
bulk and lack of tumour cell dissemination. A recent
study shows that Sema3A stimulates glioma cells
dispersal by an autocrine mechanism (Bagci et al.,
2009). Thus, it is tempting to speculate that the observed
reduction of tumour growth and dissemination in the
presence of pTM-NRP1 is the consequence of the
inhibition of this mechanism. Strikingly, pTM-NRP1
can also be used to reduce the growth of well-developed
tumours. Our data show that pTM-NRP1 can target
both the tumour cells and host blood vessels when
administrated locally (subcutaneously) or intraperitoneally thereby decreasing tumour expansion. The increas-
ing importance of NRP1 during physiological and
pathological angiogenesis recently stimulated the design
of various strategies to modulate NRP1 functions.
Function-blocking antibodies showed successful application to inhibit tumour growth and vascular remodelling (Gamse et al., 2002; Hong et al., 2007). Peptidebased strategies have already been proposed by other
groups to interfere with VEGF-A/NRP1 (Barr et al.,
2005; Slimani et al., 2006; Starzec et al., 2006; Tirand
et al., 2006) or Sema/NRP1 interactions (Williams et al.,
2005). Bicyclical peptide mimetic (Giordano et al., 2005;
Jia et al., 2006) or synthetic inhibitor (Bedjeguelal et al.,
2006) showed promising results. However, the peptide
used in this study is targeting a very particular domain,
the transmembrane domain of NRP1. This domain has
been ignored so far because of the lack of efficient tools
allowing detailed analysis of this hydrophobic environment. Although initially described for glycophorin-A
(Lemmon et al., 1992), the function of the transmembrane domain is nowadays a growing field of interest
because within this particular domain, the targeted
motif has crucial implications in diverse pathological
situations as shown by the consequence of various point
mutations of the TM domain of c-neu receptor
(Bargmann and Weinberg, 1988; Weiner et al., 1989),
FGFR3 receptor (Meyers et al., 1995; Webster and
Donoghue, 1996; Orian-Rousseau and Ponta, 2008),
FGFR2 (Forbes et al., 2002) or RET (Tessitore et al.,
1999). In all cases, the effects relate to the GxxxG motif
Oncogene
Inhibition of glioma growth using neuroplin-1 peptide
C Nasarre et al
Tumor volume increase (Vn/V1)
2388
control
+pTM-NRP1
10
5
0
0
2
4
6
8
10
days
Final tumor weigth (g)
5
4
*
3
2
1
0
Control
cont
+pTM-NRP1
+pTM-NRP1
2008) or NRP1 (Roth et al., 2008). We believe that
blockade of NRP1 transmembrane domain provides an
exquisite therapeutic tool because the biological effects
of NRP1 are significantly blocked at picomolar dosage
of the peptide (Roth et al., 2008) with a total inhibition
of the biological functions of NRP1 obtained at 10 7 M.
This peptide possesses natural targeting properties due
to its biophysical characteristics (hydrophobic) that
allow rapid integration to the targeted cell membrane.
Moreover, this peptide showed no toxicity for various
cell types in culture (including hepatocytes, data not
shown) and exhibits a very low immunogenicity profile
together with good stability (up to 48 h at the
membrane, low sensitivity to proteases when reaching
the membrane) compatible with in vivo use and
sustained efficacy. More importantly, this peptide acts
at the level of endothelial cells to prevent angiogenesis
but also inhibits tumour cell proliferation and migration
thereby interfering with the three key events favouring
tumour growth. Future investigations, together with
blood–brain barrier crossing evaluation, will address
various strategies devoted to ensure efficient systemic
delivery of the peptides for future clinical evaluation.
Although 30–50% of the drugs are currently targeting
G-protein-coupled receptors, the use of pharmacological agents interfering with the TM domain of bitopic
receptors may represent a major advance towards the
design of new classes of efficient therapeutic agents for
cancer treatment (Bennasroune et al., 2004) or other
pathological areas such as neurodegenerative disorders
(Marchesi, 2005). To our knowledge, pTM-NRP1 is the
first drug of this kind that shows a therapeutic potential.
Materials and methods
Figure 7 Local administration of pTM-NRP1 inhibits human
glioma growth. (a) Heterotopic xenografts of U373MG human
glioma cells. Visible tumours were obtained 3–4 days after
transplantation. At this point, we performed daily subcutaneous
injections of phosphate-buffered saline (PBS) (control) or pTMNRP1 (10–7 M). The experiment was stopped after 10 days
treatment on decision of the veterinary in charge of the animal
facility based on too strong diminution of grooming, general
mobility and loss of body weight in the group of control animals.
Tumour growth was monitored in blind conditions every day using
a calliper. The graph represents the daily average tumour volume
from 19 control and 20 treated tumours. (b) Box plot representation. Results represent tumour weight determined immediately
after resection of the tumours. In each box the dark lozenge is
showing the mean, the vertical bar the median. Statistical analysis
confirmed the significance of the measured reduction of tumour
weight (*Po0.05). (c) Microphotograph showing the reduced
perfusion of treated tumours.
(or equivalent small amino-acid-xxx-small amino-acid
motif) that is supposed to drive the dimerization of the
transmembrane domains (Senes et al., 2004). This has
been clearly shown for APP (Kienlen-Campard et al.,
Oncogene
Cell lines
Cells were grown in a 5% CO2 atmosphere, at 37 1C. C6 cells
(ATCC CCL-107) come from rat glioblastoma. They were
grown in modified Eagle’s medium (Fisher Scientifique,
Illkirch, France) with 10% fetal calf serum (SVF; Interchim,
Montluc¸on, France), glutamine 0.5 mM (Fisher Scientifique)
and antibiotics: 100 U/ml penicillin and 100 mg/ml streptomycin (Sigma). Human glioma cell line U373MG (our
collection) was cultured in DMEM supplemented with 10%
fetal calf serum.
Peptides
Peptides have been synthesized within the Neurosciences
IFR37’s proteomic facility by Mr B Guérold, by automatic
peptide synthesis (Fmoc chemistry; Applied System, Courtaboeuf, France), and have been analysed by mass spectrometry.
One peptide is the transmembrane sequence of NRP1:
ILITIIAMSALGVLLGAVCGVVLYRKR (TM peptide). In
the second one, glycines have been replaced by valines:
ILITIIAMSALVVLLVAVCVVVLYRKR (mutated TM
peptide) (Roth et al., 2008). Peptides purity estimated by
RP-HPLC (Beckman, Roissy, France) is more than 90%.
Magnetic resonance imaging
MRI acquisitions were performed with a 4.7 T, 20 cm system.
The magnet and gradient coils are from Magnex Scientific
Inhibition of glioma growth using neuroplin-1 peptide
C Nasarre et al
2389
control
-7
+pTM-NRP1 10 M
Isolectin-B4
IsoB4 positive vessels/mm2
20
10
0
**
cont
+pTMNRP1
CD31 positive vessels/mm2
CD31
20
10
**
0
cont
+pTMNRP1
CD34 positive vessels/mm2
CD34
20
10
0
**
cont
+pTMNRP1
Figure 8 Anti-angiogenic effect of pTM-NRP1 in vivo. Histological analysis of tumours. We used isolectin-B4, CD31 and CD34 to
stain blood vessels in the tumour bulk. All three markers allowed us to visualize hot spots composed of several blood vessels. We
determined number of blood vessels per mm2 by counting vessels from all hot spots present on three different slices (randomly chosen)
from three different tumours (reflecting the smallest, medium and largest tumours of the two groups). Scale bar ¼ 100 mm. **Po0.001.
Ltd. (Oxon, UK) and the MR spectrometer from SMIS Ltd.
(now MR Solutions Ltd., Guildford, UK). We used a fast
spin-echo imaging sequence consisting of 15 contiguous
coronal slices acquisition with a 3.8 s repetition time. Four
echoes were recorded with a 40 ms spin-echo time and a 80 ms
effective echo time, the second echo being located at the centre
of K space. The slice thickness was 1 mm, and the field of
view 40 40 mm2 with a data matrix 256 256, leading to a
resolution of 156 mm. The number of acquisition for each
profile was fixed to 2. The resulted acquisition time was
approximately 8 min.
In vitro assays (proliferation, migration and angiogenesis)
C6 or HUVEC cell aggregates were prepared as previously
described (Nasarre et al., 2005) to be grown in the 3D matrix
(plasma clot) and treated with VEGF165 (100 ng/ml; R&D,
Lille, France). For the proliferation and cell death assay,
the cells were incubated at a known density in 60 mm
dishes (Dutscher, Brumath, France) (100 103 cells). MTT
(Promega, Charbonnière-les-Bains, France) and tube-like
formation assay (in vitro angiogenesis assay; Chemicon) were
performed using manufacturer’s instructions. Oligomerization
assays were performed as previously described (Roth et al.,
2008). RT–PCR were performed at 30 cycles, Tm ¼ 58 1C
using NRP1 sense 50 -ACAGTGGCACAGGTGATGAC-30 and
NRP1 anti-sense 50 -TCCAGGGCAGATAGGTTC-30 primers.
Chick embryo chorioallantoic membrane assay
The CAM assay was performed using Leghorn embryonated
eggs. After 4 days incubation, the embryos were transfer to a
Petri dish. The CAMs were grown for additional 4 days before
deposition of reservoirs in a region containing one large vessel.
Reservoirs were filled with 20 ml solution of PBS, pTM-NRP1
(10 7 M), pTM-NRP1mut (10 7 M), VEGF165 (20 mg/ml) or
combinations of these factors. After 24 h incubation, micro-
photographs were taken for quantification of vessel growth.
Camera lucida drawing was systematically performed to allow
better counting of new blood vessels and sprouting; the entire
analysis being performed in blind conditions.
In vivo assays (orthotopic and heterotopic xenografts)
We conducted all in vivo experiments under the supervision
and control of the veterinary in charge of the animal facility
of the Centre for Neurochemistry (IFR37, Strasbourg) in
accordance with the Guide for the Care and Use of Laboratory
Animals (NRC, 1996) and the European Directive 86/609. C6
cells (ATCC CCL-107) were stained before transplantation
using PKH26 and according to manufacturer’s instructions
(Sigma). Cells were incubated with peptides (pTM-NRP1
10 8 M or pTM-NRP1mut 10 8 M) before injections for at least
2 h on ice in culture medium (composed of modified Eagle’s
medium with 5000 U/ml penicillin, 5 mg/ml streptomycin,
200 mM L-glutamine and 10% fetal calf serum). Rats (Janvier,
France), all males weighing 250–350 g, were anesthetized
by IP injection of a mixture of tiletamine-zolazepam
(50 ml/100 g) (Zoletil 100; Virbac, Carros, France), and
xylazine (50 ml/100 g) (Rompun 2%; Bayer, Puteaux, France).
Cell suspensions were implanted using a stereotaxic set up at
the depth of 5 mm, 1 mm anterior to the bregma and 3 mm
lateral corresponding to the anterior striatum with a 10 ml
Hamilton syringe. After injection, the needle was kept in place
for 5 min, then slowly removed at 0.5 mm/15 s. The scalp
incision was closed with stainless steal wound clips and the
animals allowed recovering under a heat lamp before they are
returned to their cage. All injections were performed in the left
striatum. After a survival period of 8 days, the animals were
killed by a lethal IP injection of pentobarbital before transcardiac perfusion with a prerinse of 100 ml PBS followed
by 500 ml of 2% formaldehyde. Heterotopic tumours were
produced by injecting 106 cells in the flank of pathogen-free
Oncogene
Inhibition of glioma growth using neuroplin-1 peptide
C Nasarre et al
2390
(Berthold) equipped with dedicated anaesthesia chamber and
appropriate filters for fluorescence detection.
Histology and immunocytochemistry
The brains were postfixed during 2 h at 4 1C and sagittal
sections (70 mm) were prepared on a vibratome. One group of
sections was mounted in PBS-glycerol (v/v) for microscopic
observation, and another one was treated for immunostaining.
Ectopic tumours were embedded in PEG before immunoreactions as previously described (Klosen et al., 1993). Sections
were first incubated in PBS containing 5% calf normal serum
for 15 min at room temperature to block nonspecific binding
sites. A second incubation was performed for 1 h at room
temperature and then overnight at 4 1C with appropriate
primary antibodies (anti-mouse CD34 or anti-mouse CD31;
Clinisciences s.a.s, Montrouge, France) or 30 min at room
temperature for Isolectin-B4 (FL-1201; Biovalley, Meaux,
France) staining. The sections were washed six times during
5 min in PBS, and were then incubated with secondary
antibody coupled to Alexa-488 (1:500; Interchim) for 3 h at
room temperature. Sections were washed six times during
5 min in PBS and were finally mounted in PBS-glycerol (v/v)
before microscopic analysis. In case of IP injections of RhodpTM-NRP1, tumours were collected 20 min after injections,
fixed and sliced for direct observation of slices using
appropriate epifluorescence microscope.
Tumor weigth (g)
4
3
*
2
1
0
ntr
co
ol
P1
NR
TM
+p
Figure 9 Intraperitoneal administration of pTM-NRP1 inhibits
human glioma growth. (a) Distribution of rhodamine-conjugated
pTM-NRP1 15 min after IP injection shown by in vivo live imaging.
The intensity of staining is indicated with a color code (blue ¼ low
to red ¼ high). The two Eppendorf tubes seen on the picture show
the test solution (Rhod-pTM-NRP1 in PBS) and a control solution
(PBS). Note that the tumour mass seen at the dorsal part of the
mouse is stained with the peptide. (b) Histological examination of
tumours from animals receiving Rhod-pTM-NRP1. Note that
intratumoural blood vessels and adjacent tissue are stained with the
peptide. (c) Daily intraperitoneal (IP) injection of pTM-NRP1 is
able to reduce the growth of well-developed tumours (U373MG
human cell line) implanted into the flank of nude mice up to 50%
(*Po0.05).
BALB/c nu/nu mice (Charles River Laboratories, L’Arbresle,
France) maintained in individual cages. For that, the mice, all
males or all females, were anesthetized in a Plexiglas box
flushed with oxygen containing 3% isoflurane, and then
maintained anesthetized by 2% isoflurane inhalation using a
facial mask. The cell suspension was taken into a 1 ml syringe
and transplanted in the flanks of the mouse subcutaneously
(100 ml, 106 cells). Live imaging of fluorescent peptide
distribution was performed using the NightOwl bioimager
Oncogene
Statistics
We performed two independent samples comparison using
Student’s t-test for n430 and Mann–Whitney analysis for
no30 for quantitative data (number of cells, tumour
weight, number of vessels, number of branch points). Normal
distribution of the values was checked using GraphPad software
(Curri, Strasbourg). We performed w2-analysis for qualitative
data (presence or not of chains of cell migration). A minimum
of three independent experiments was performed for in vitro
assays (proliferation, migration and angiogenesis). The number
of animals used for in vivo analysis takes into account ethical
reasons. Sample size calculation was determined by postulating
an effect size of 20% (d, differences between two means of
tumour volume) given an allocation ratio of one (similar-sized
population) and using continuity correction (Uitenbroek, 1997).
We used power ¼ 0.8 and a ¼ 0.05. Thus, the data presented are
from one experiment for MRI acquisition composed of three
controls and three treated rats (Figure 1a), three independent
experiments composed of three experimental groups of animals
for histological analysis of orthotopic brain tumours (giving
a total of 12 control, 12 pTM-NRP1- and 7 pTM-NRP1muttreated rats, Figure 1b); one experiment composed of two
groups of 10 mice (giving a total of 19 heterotopic control
tumours and 20 heterotopic-treated tumours for U373MG cells,
Figure 7; one dead animal at day 6 was excluded from control
group). In all experiments, animals were randomized before
treatment delivery that was performed in blind conditions. The
experiment performed with U373MG cells has been stopped
after 10 days treatment by decision of the veterinary in charge
of the animal facility due to serious impairment of living
conditions of the mice of one of the two groups (retrospectively
identified as the control group).
Conflict of interest
The authors declare no conflict of interest.
Inhibition of glioma growth using neuroplin-1 peptide
C Nasarre et al
2391
Acknowledgements
We thank Dr Sophie Reibel-Foisset and Mr Nicolas Lethenet
for excellent assistance with in vivo experiments and animal
care. This work was supported by INSERM, ACI JC
(No. 5327), ARC, ANR Emergence bio, FRC/Rotary international to Dominique Bagnard. Cécile Nasarre was supported by Pharmaxon and La Ligue Contre le Cancer.
References
Bagci T, Wu JK, Pfannl R, Ilag LL, Jay DG. (2009). Autocrine
semaphorin 3A signaling promotes glioblastoma dispersal.
Oncogene 28: 3537–3550.
Bagri A, Tessier-Lavigne M. (2002). Neuropilins as semaphorin
receptors: in vivofunctions in neuronal cell migration and axon
guidance. Adv Exp Med Biol 515: 13–31.
Bargmann CI, Weinberg RA. (1988). Oncogenic activation of the neuencoded receptor protein by point mutation and deletion. EMBO J
7: 2043–2052.
Barr MP, Byrne AM, Duffy AM, Condron CM, Devocelle M,
Harriott P et al. (2005). A peptide corresponding to the neuropilin1-binding site on VEGF(165) induces apoptosis of neuropilin-1expressing breast tumour cells. Br J Cancer 92: 328–333.
Bedjeguelal K, Bienayme H, Dumoulin A, Poigny S, Schmitt P, Tam
E. (2006). Discovery of protein-protein binding disruptors using
multi-component condensations small molecules. Bioorg Med Chem
Lett 16: 3998–4001.
Bennasroune A, Gardin A, Aunis D, Cremel G, Hubert P. (2004).
Tyrosine kinase receptors as attractive targets of cancer therapy.
Crit Rev Oncol Hematol 50: 23–38.
Forbes LV, Gale RE, Pizzey A, Pouwels K, Nathwani A, Linch DC.
(2002). An activating mutation in the transmembrane domain of the
granulocyte colony-stimulating factor receptor in patients with
acute myeloid leukemia. Oncogene 21: 5981–5989.
Gamse JT, Shen YC, Thisse C, Thisse B, Raymond PA, Halpern ME
et al. (2002). Otx5 regulates genes that show circadian expression in
the zebrafish pineal complex. Nat Genet 30: 117–121.
Garcia-Verdugo JM, Doetsch F, Wichterle H, Lim DA, AlvarezBuylla A. (1998). Architecture and cell types of the adult
subventricular zone: in search of the stem cells. J Neurobiol 36:
234–248.
Giordano RJ, Anobom CD, Cardo-Vila M, Kalil J, Valente AP,
Pasqualini R et al. (2005). Structural basis for the interaction of a
vascular endothelial growth factor mimic peptide motif and its
corresponding receptors. Chem Biol 12: 1075–1083.
Goldbrunner RH, Wagner S, Roosen K, Tonn JC. (2000). Models for
assessment of angiogenesis in gliomas. J Neurooncol 50: 53–62.
Grobben B, De Deyn PP, Slegers H. (2002). Rat C6 glioma as
experimental model system for the study of glioblastoma growth
and invasion. Cell Tissue Res 310: 257–270.
Guttmann-Raviv N, Kessler O, Shraga-Heled N, Lange T, Herzog Y,
Neufeld G. (2006). The neuropilins and their role in tumorigenesis
and tumor progression. Cancer Lett 231: 1–11.
Hong TM, Chen YL, Wu YY, Yuan A, Chao YC, Chung YC et al.
(2007). Targeting neuropilin 1 as an antitumor strategy in lung
cancer. Clin Cancer Res 13: 4759–4768.
Hu B, Guo P, Bar-Joseph I, Imanishi Y, Jarzynka MJ, Bogler O et al.
(2007). Neuropilin-1 promotes human glioma progression through
potentiating the activity of the HGF/SF autocrine pathway.
Oncogene 26: 5577–5586.
Jain RK, di Tomaso E, Duda DG, Loeffler JS, Sorensen AG,
Batchelor TT. (2007). Angiogenesis in brain tumours. Nat Rev
Neurosci 8: 610–622.
Jain RK, Duda DG, Clark JW, Loeffler JS. (2006). Lessons from
phase III clinical trials on anti-VEGF therapy for cancer. Nat Clin
Pract Oncol 3: 24–40.
Jia H, Bagherzadeh A, Hartzoulakis B, Jarvis A, Lohr M, Shaikh S
et al. (2006). Characterization of a bicyclic peptide neuropilin-1
(NP-1) antagonist (EG3287) reveals importance of vascular
endothelial growth factor exon 8 for NP-1 binding and role of
NP-1 in KDR signaling. J Biol Chem 281: 13493–13502.
Jocic Z, Staton RD. (1993). Reduplication after right middle cerebral
artery infarction. Brain Cogn 23: 222–230.
Kelland LR. (2004). Of mice and men: values and liabilities of the
athymic nude mouse model in anticancer drug development. Eur J
Cancer 40: 827–836.
Kienlen-Campard P, Tasiaux B, Van Hees J, Li M, Huysseune S, Sato
T et al. (2008). Amyloidogenic processing but not amyloid precursor
protein (APP) intracellular C-terminal domain production requires
a precisely oriented APP dimer assembled by transmembrane
GxxxG motifs. J Biol Chem 283: 7733–7744.
Klosen P, Maessen X, van den Bosch de Aguilar P. (1993). PEG
embedding for immunocytochemistry: application to the analysis of
immunoreactivity loss during histological processing. J Histochem
Cytochem 41: 455–463.
Lemmon MA, Flanagan JM, Treutlein HR, Zhang J, Engelman DM.
(1992). Sequence specificity in the dimerization of transmembrane
alpha-helices. Biochemistry 31: 12719–12725.
Marchesi VT. (2005). An alternative interpretation of the amyloid
Abeta hypothesis with regard to the pathogenesis of Alzheimer’s
disease. Proc Natl Acad Sci USA 102: 9093–9098.
Meyers GA, Orlow SJ, Munro IR, Przylepa KA, Jabs EW. (1995).
Fibroblast growth factor receptor 3 (FGFR3) transmembrane
mutation in Crouzon syndrome with Acanthosis nigricans. Nat
Genet 11: 462–464.
Nasarre C, Koncina E, Labourdette G, Cremel G, Roussel G, Aunis D
et al. (2009). Neuropilin-2 acts as a modulator of Sema3Adependent glioma cell migration. Cell Adh Migr 3: 383–389.
Nasarre P, Kusy S, Constantin B, Castellani V, Drabkin HA, Bagnard
D et al. (2005). Semaphorin SEMA3F has a repulsing activity on
breast cancer cells and inhibits E-cadherin-mediated cell adhesion.
Neoplasia 7: 180–189.
Orian-Rousseau V, Ponta H. (2008). Adhesion proteins meet
receptors: a common theme? Adv Cancer Res 101: 63–92.
Roth L, Nasarre C, Dirrig-Grosch S, Aunis D, Cremel G, Hubert P
et al. (2008). Transmembrane domain interactions control biological
functions of neuropilin-1. Mol Biol Cell 19: 646–654.
Senes A, Engel DE, DeGrado WF. (2004). Folding of helical
membrane proteins: the role of polar, GxxxG-like and proline
motifs. Curr Opin Struct Biol 14: 465–479.
Slimani H, Guenin E, Briane D, Coudert R, Charnaux N, Starzec A
et al. (2006). Lipopeptide-based liposomes for DNA delivery into
cells expressing neuropilin-1. J Drug Target 14: 694–706.
Starzec A, Vassy R, Martin A, Lecouvey M, Di Benedetto M, Crepin
M et al. (2006). Antiangiogenic and antitumor activities of peptide
inhibiting the vascular endothelial growth factor binding to
neuropilin-1. Life Sci 79: 2370–2381.
Taguchi A, Soma T, Tanaka H, Kanda T, Nishimura H, Yoshikawa H
et al. (2004). Administration of CD34+ cells after stroke enhances
neurogenesis via angiogenesis in a mouse model. J Clin Invest 114:
330–338.
Tessitore A, Sinisi AA, Pasquali D, Cardone M, Vitale D, Bellastella A
et al. (1999). A novel case of multiple endocrine neoplasia type 2A
associated with two de novo mutations of the RET protooncogene.
J Clin Endocrinol Metab 84: 3522–3527.
Tirand L, Frochot C, Vanderesse R, Thomas N, Trinquet E, Pinel S
et al. (2006). A peptide competing with VEGF165 binding on
neuropilin-1 mediates targeting of a chlorin-type photosensitizer
and potentiates its photodynamic activity in human endothelial
cells. J Control Release 111: 153–164.
Uitenbroek DG. (1997). Binomial SISA. http://www.quantitativeskills.com/sisa/distributions/binomial.htm.
Oncogene
Inhibition of glioma growth using neuroplin-1 peptide
C Nasarre et al
2392
Uzzan B, Nicolas P, Cucherat M, Perret GY. (2004). Microvessel
density as a prognostic factor in women with breast cancer: a
systematic review of the literature and meta-analysis. Cancer Res 64:
2941–2955.
Wang AC, Dai X, Luu B, Conrad DJ. (2001). Peroxisome proliferatoractivated receptor-gamma regulates airway epithelial cell activation.
Am J Respir Cell Mol Biol 24: 688–693.
Webster MK, Donoghue DJ. (1996). Constitutive activation of
fibroblast growth factor receptor 3 by the transmembrane domain
point mutation found in achondroplasia. EMBO J 15: 520–527.
Weiner DB, Liu J, Cohen JA, Williams WV, Greene MI. (1989). A
point mutation in the neu oncogene mimics ligand induction of
receptor aggregation. Nature 339: 230–231.
Williams G, Eickholt BJ, Maison P, Prinjha R, Walsh FS, Doherty P.
(2005). A complementary peptide approach applied to the design of
novel semaphorin/neuropilin antagonists. J Neurochem 92: 1180–1190.
Xu L, Duda DG, di Tomaso E, Ancukiewicz M, Chung DC, Lauwers
GY. et al. (2009). Direct evidence that bevacizumab, an anti-VEGF
antibody, up-regulates SDF1alpha, CXCR4, CXCL6, and neuropilin 1
in tumors from patients with rectal cancer. Cancer Res 69: 7905–7910.
Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)
Oncogene
9BBF
9
)
;94:9'
'
''
+
$$
<
#
!
"
6
/.&
# $ !"#$ % & '
()&*$+*!
,)-$.
(*
(*$/*),)0
$ &* 1$ /223 %$
$/22-
+ . !"#$
%&
! -
-
'&'()*
!
+,
/0
)'1
-
+ &
023.
#
6
/+&
*
! "# "$%
"
#&"$%
.%4.9
;. $#
" & 9% 4.9
;.
+
' ) ;94:9 ' '" ' ) * ) , ' '
' ' )* -" - = 9
) )' "H'
- '
) '' '
+
+ ' )
'@'
'"HH
+
@/'-
5
)
' '
- '
' ' ' '
+
)'
>
)8%'')*)
'
) " - )* )
'
(
'*)
! 9 9#% *' +
*
) ' '3' ! 90 9% /" ' *
, )* * * ) ' ' ! 9 9#% ' ' 4
)
,'
')
)
))
'
B 3'!
)%
"
*
,9<
)H
!999%
$0
< =D >
+..
:A
A.
'0!+
=+.0:'>
6
/-&
"*
'0!+
#3
$3
!"#$%&'()
)*+,-*./.0+&)'0
1
2)
324*50000.
H
## _ 9= )
! " ' ( , $ _% S" ;94:9!,
# $ %"
@'
H
" (* ) * '( . 9 +
) ')
=
5B;-!
(
% 7##' = '+
(
+
,''+#
'
,
o-
'
*
)
'
,
' ' ' '
!M M
+% '
D '
P B' P ' P @*
-' + !/*F 0& '" /'F &#
'% '
D E' ' +)
+)
9
' ;94:9" H ( , ( S
);94:9 "'+?,0'
'
) ' + ) ) + !
) +%
'
,'
(
S
"
''##."'
''
+ ! '
' )' )
' % '
'
)0".!j####%
'
) ) ;94:9 ,
S!
) 2%-
'+'
''3''
"
M/65!:
%
+
0 . , # '7L !=
" #%" &### ;94:[email protected]"'
)
'
3;94:9
' ' , '
H,
-
'' )
) ! BB%" 4:9
) M/65: ' ' *" )
M/65: M/65 - )
M/65:
$A
% 6 0- D
7
77
+..
A.
.
%
6
%
6
E
'
0!
6
//&
"*
'0!+
5
%60-
!" #! $%& ! '()
*!+%,-./,00120
*!.343,0.,00120
.5
67738000673800
'
+)
;94:9,
) +
' @" H ) M/65: ' ! >OM/-% ' (
;($&
' '
!K " ##0% 1 ,
(' 2 /B @ ) (
)) '
,
M/65!
''##.
*% *' . , ) ' ' ) !$ _% ' " )
+) +
(
) + )
' ) M/[email protected] , ## 7' #
'
(
M/65:'&$.!j#"##%
,
S);94:9,#$ ' ) M/65 , ## 7' # ' '
'
) &"0 . !j#"#&% (
M/65: , M/65
,
"'3''
'++"
'
)
4:9)
6'
'
'
) (
M/65: . , #
_7'!9"##$%
@")'
4:9
'
(
M/65:
M/65
+ 4.9;. 6 ;94:9 H, '
) * 5:/; ' ) '3' ) '''+6(
@"
'
6***6"
) )
' ' ''+ 4:9 g )
' ( ) '
6***6***6 !:
" ##0% 4:9p 9
, " * =
4
)
* ;94:9 ' ''+ *
0#
$
"
%
1
6
#
!
!
F
+
+
+
+
!
" = :..
B..
A..
@..
/..
-..
+..
.
0+..
0-..
6
/@&
'
$
'0!+
*
**
!" !" #$ G0
1
<
!+
-= 0 >
+. 0 +
+. 0 -
D ++,
+..
;.
/:/
,.
:.
B.
+3.+. 0 ;
+3.+. 0 ,
+3.+. 0 :
+3.+. 0 B
='>
6
/A&
1
!+
++,
'%
*
'0!+
<3
#
!"#$$%&"&"'
(%&')$"""*+*" %&,'"&-
%" ' " ' % %%" . "&"' &"& / 0
'&1""23&"""-
4555
('
'
4
)
+)
'
'
4:94:9!
)*%-
''+
)
'4:9,
) 4:9 4
)
)
# . ) '''+4:9)
$"?.)
'
''+ 9*@ 9 " +) ) ' ''+M/65: \-'
;94:9 ) )4:99*@')M/65:\
) ( 9 4.9;. #$
;94:9++
"'
'
+
'"-?
+
'
'" O$6 !4 " ##% )
")'
*' ' * O06 *'
' 4:9 / " )
) *
4:9 ''
(
':;e9-:!
)0+)02%*
4:9 * O06 * O$6 B
)
";;'
O06)'
, #$ !j#"###% '*''"A.,
# ?!
)0"%
9
)
))
" H '
O06 - '
*''
'
-
')
'
'
+
''
)
('
H
# H
, H
g ' )
' ## '' ' H
## _ 9= ) ! , $ _%" ;94:9 !#$ % )1+ '
'
'
'
!)
')
''
0
* * D
1"
I<
(-.2(.
+...
;..
,..
@..
/
/
#, %
# ".67$&"%
/..
-..
+..
.
0+..
-.
+A
+.
A
.
.
A
+.
+A
-.
1 H *
1 H *
-.
+A
+.
A
.
!+
+.0:'
6 /B& "* '0!+ * * <<
)
0
++,
'%# !" #$% !" & &" " " '" " ( &") '" "* $3
+&' ," &! "&" -'".
"" /0"3 -
& -
'" 1 1/. 1 1. 1 1/ 1 1 "-
& &2 11.3
'"#
4)5.%
)3,%6 % 4.9;.
' ' H
' , '
( ' '
S%" # . '* '
)
!
+ " " :/-B ;% A# . !
9 :
9:" :/-B ;% 4
)
)
* ' ' '
;94:9 S" *
)'!j#"###%!
)1"%"
* ' ' ' !W#7W#%" )
+) ) !j#"#&% B ' "?? S!U#%,?"#
);94:9!U#%!
)1/% -
)* ) ;94:9 + '
'
* # &
$#
)
'
' ' " ' '' ) @,
'
'' ! +
"
'
) ' ' ''+%" '
@" )
'+ ) ' ''+ 4:9!
)3%'
!9-4:9%
)4'
'''+
''
6***6*'
!9-4:9%
)-'
'''+)
*' '
6***6 ' !9-4:9% -'
'''+')*'
6***6
-
+H)
)+
0
! * H =D >
+..
A.
.
+
>
-
>
/
>
'
!
!
'
@
>
+
'
A
+
!
>
'
+
"
!
+
6
/,&
8
*
*
! " "#
6
/;&
*
/:/
'%3
!"# $ %&& ' ( )
*
+,-& &. /0
* 4 9% B:("
*" ' ) ;94:9 '
) 0 . S !j#"##% '+ !
)5% H
9-4:9 )
'
) & . !j#"###% '+ " 9-4:9 9-4:9 '
'
) ? . !j##&% '+ S"'+;94:9
!9-4:9%
+
';94:9
* 49
9
)'
'
'
H
O$6 ) M/65
''
'' I
J * ] '
M/65" IJ + ] '
S"'
)M/65##7']&.
!
)7%;94:9)'
, # . !j#"#&% ' " ' ' )' !j#"#&%" &.,#.
9-4:9",&.
9-4:9
,0.
9-4:99-4:9'
;94:9!j#"#&%;
'+''
'
'
;94:9
*) 49
5'" H '
O$6
IJ
)'
'
*"
'',
#H
')
!
*8+
*82% '
( ' S #"& !U0%" 0
+3A
+3.
.3A
/
-
$
.3.
+
6
@.&
"*
*
<<
0
)
/:/'%3
# $ !"
) 9-4:9 #"? !U0%" )
*
9
"
'
('
9-4:9
)',#"A?!U0%!U#"##A#%'3''
9-4:9 )' , #"# !U0% !U#"##% 9
'
*
'
))
0
9BBBF
+
9*@+
' ''+ )
'
'
+
'
0&
&$# .9+ #
# & #
:'F
+
''+")
')')
&'
'
'
*"
'
'
*
9*@
))
')
')
+
'4
)
'
'''+9*@,
'
'
''
')4
"9*@"9*@9*@@
)
)
+";99*@"''
'''+9*@ +
+
;99*@'
4:99*@9*@
9*@-+')
9*
@ '' : '' @C; (
M/65: 4
)
9*@)*+
6=-*
')*
)
'('+'
))
B'+
9*@H
S
"S
'
;99*@+
'
+)
"
+
'
)
'
)*))
''+
D'+(
";99*@'
'
6=
'!O$6"O06%"+
'
')
<
"'
'
'
O$6O06
(
'",'9>-"
'
))
+
'
'
'
*'
)4
)
'
'
*
9*@
!4->?%;99*@+
'
!+
)'
'
%)
'3
'
',
0?
'
4->?
8
/
"'
9*@'
6=
*
'
+ ' * ,
+
'''+'
+
'
+
"'
"
'
-;99*@
''+
''
'6=
0$
!"##$%&#'#
()!#!*#+*&%#
#,% % -# .//01 -'%2 # ( .//31 - 4 ./0/14 5 6, # %
,
# # 6 7
,
% # 6, 6
% , % %
64 ,
8
2#6,#
6
, % #% % # #
-&, 4 ./001 -&# 4 ./0.14 %6
%%##, 6%# ##%
2% 6
#% , 2 -22 #
./091 2% ,
-# 4 .//:1 -)# 4
./0014,
#,,,6 # ,#-)#2##./0/1-&6#74./0.1-;
4./0914
##6% %##, 66
6%4
,8###%
6 %6 ,# ,#66
,8 # 6 #% #
##,66
#, #%
#
8%## #<
%% 4%%*
8 6# # 6 # #
## 6% % % 6 -4./0914## ,
%% * 2% #,% 6 * 6 %
#
6 2 -)(1 # # %4 = 6
% 6 # 6 %7 6
6 # # # % # ,
% 6 % #
- # , ./0/1 - 4
./0/14 =## 6 # -+1 , #
#6)(
#%>&6 -#
#./0/1#
6
%-?./0/1# "
-(6 4 ./0/1 7
% - 4 ./0/14 %%
+ * , % #% #% %% 8
# 6 4 = 8 #+6 70 6##%6
-)4.//@1
%#%6%
6
-&%
4
.//:14 2% # 2% +6 )0 -7)01 %% #4 )0 8 # % #
9"7# # # 6 -&%
4 .//:1 #
5>7## % ,, -2 4 ./0.14 6#7)0 #
%#%%,#
,,#
%%-4./0/14%%
#+ ,
6 %-%,./0/1#
+76% # 6 %-
4./0/1462
#
#66+
6
#
7#4 , 6 % %% # 6 + 7
-? ./0/1 # 6 A6 6
%6%7#
62%%
4&#
7)0 #
## 6 8 6
%%%% 6 70##, 6 #
#%# 6 6 )0 #
%66%%
2%
4
87"0 6 2 %% 6 )0
-%40:::1-)4.///16
%
26%
,,4?%
#7#2-&"1
)0<87"0 + # 4 # 2% + 6 87"0 -78"01 #
#
% 6 # 2# 5>7#
# #4 66
#
*
6 # 6 )0<87"0 # #
6 87"0 )7 ,4 ,, ,# 6
78"0 ,# 7%%
, 6 87"0 8 % 6 %
,6 #4',##687"0,2
6 % , # , % 6 , #, # 6
4
)0 #%%#
%%,
-&#.//B1-+%4.///1-'#4.//B14,)0
2
%% , # * %% %% %
6
-#C # 2 ./0.14 = 6 %% # 8 6 )0 % % 6
# 2 %
4"%87"0 # %#
6%%
#6# 6 )0 # , # ## -% 4 0:::1 -2 4 0:::1 -) 4 .///14
2 %% % # , #
# 87"0 6 7# # % % -
4 ./0/14 ## , , 6 6 % 6# # % 6 )# # "
-#, 4 .//:1 -
" )
2
.//@1-%0"0&14'6# ##6 ,[email protected]#
B:: % # 8 % % , 6 87"0 # #
#
6 ,, # 8 % , 6 87"0
- E/4/B0)#
# E/4//3"
%7214
8 6 %
, 6 87"0 6# 7 -?
&81 6 .:3 6 -% 014 *,687"08 ,#
%#6
%#,68 6
4=##,6#
%# -"
%# =1 % % %# % -1 8# % 8 4 # == # %# === # , 6 87"0
%#%#=#=5-%0+142%,8 687"0
% 6# ,% )7F)
,# /4:0 [email protected] 6# 6 87"0 6 @ C
-% 0>14 ; #6% 87"0 %
<#%
2 6%%# 87"0 # %% 6 )0 8 6
%%4
'#%#%%6% #6
# 6 ,,# % %4 % # # # 6 8
6 + 4 6 )0 #
8"0# 6#+'##
6
#6#66#42%*#6
6 6 +0 )07+. )0 # 8
#% 3 H -% ."
14#
#%##
%%6 7
9.I ,%4 -% ." 1 # # 7#6#
% 6 0.8880G888./ #
# /43 4 ' H +9 8"0 # +0 )07+. )0 # 6 #[email protected]%.&#. 14
%%J99I
# JBI ,% 6 # +. )07+9 8"0 # +0 )07
+98"0 ,4+.)07+98"0
8#2
6
# "00 # "0B 6 +. )0 # : 6 +9 8"0 -
#
#/431-%.&14
#
#
/4D,# +0)0-5..#5.G1#+98"0-5./#
".91 -% . 14 " , 6 6 %
9"4 ; % 6 +0 )07+. 8"07+9 8"0
, *
2 - 0 H1 ,# 6 6 +0 )07+.
8"0 # -% .+ 14 + # % ## %%6 799I,%4.GH+98"0 #66#
#A#+0)07+.8"0#6
# 6 -B/ H1 -% .> # . 14 +0
)07+98"0##+.8"07+98"0#
#
% ## % % * 79GI # 7B3I ,4 8# % 6 0.8880G888./ 6 +0 )0 # 2 # 00 03 # 0: 6 +. 8"0 # +9 8"04 " ,
6 6 % 9&4 % %9)0+#987"0+#
%#
# 6 7# 8 , % -% .14##% # 2%+687"0
# % + #% %
#
4
6 8 + 6 87"0 # 7# 2
% 6 6 + - 4 #
,14 + *
6 87"0 # , % #%
)0 # 6 87" 6 78 # #6 6 4 8 6# ## %6
)0 # 87"0 + -% B"14
6# 2 %6
7# 6
87"0 # ,# , + 6 87"B ,
# 87". # 87"94 "## #% + 6
87&0
>5>)705>)7.5>)79">).=%&0#
%6
87"0+ 6
8887
26-%B&14
"6
)
-)&
1
#
# 87"0 ##
4#
6&",
87"0 + # %6
# )0 -
, 6 &" 1 5>)7. -
%,
6&"1-%B14= C#
#
6 #
2%+ 8 #66
6 # 6 # #% 8
# 6
466
#+ #6
#
8 6
64
!
" , # % % # #<
%6
##%6% #
%
+ 6 4 # 78"0 8 6 6# 8 % -+72 %7"#
1 -#*, 4 ./0914 " 6% 3" ,# 70<87"0 8 6
#4 , ##678"0#
#.:K#
66 70<87"0
84,6#9"7#
#
7 687"0
)0%6
#
# 678"0-%3&14##
6 # 2# 7 6 87"B 5>
-%314
%#78"0 # , % 6 87"0 % # ,
%#4
" 87"0 )7 ,% 4 9" )7 )
0 ,# # *# -4.//B1-#&
2./0.14%>="7#-)L+1
78"0 %6
# 9"7#
# )
0 ,
66
%)7
,
6%#-%G"14,
9""2 %#%6)#0
87"04'#9"7#
#6"2 2#
##678"0-%G&14,#%%# 7%%
66
687"0-(%4./0014=##% 65>)7.
%>="6#78"0%6
#
#5>7#
#
65>)7.-%G14
78"0 % A
%% 687"0
4
#"
" ,#
2%%# %%
687"0
-(%4./0014; 78"0 5>7##5>)7
. 42%,#87"0 ,#,
6 % -% D"14 =% # , 8 %87"04 "##8 6# # #, % # # , 8#
87"0 , % - 6% 014 #
%%#687"0#%# %
%%4
6
6 6# #7 6 ?5> % %4=## 6###6 78"0%6
2#72
[email protected] E ///@D1 -% D&14 6 5>7#
#
?5> % 6# , % 7 -7G9K E ////.MN7%
">"&
-4./0.1-+4.//@1
-% D14 , 9+ % > # % # 5>7#
# % # ##% 87"0
# -% D+14 6 ,# 7%%
, 6
87"0 # ,
#, 6 7
6
2 4 = 6# 8 6 87"0 #, % #
, -% @"1 # # # 6 78"0 %6
#5>7#
# ,
%#
8-%@&@14"%
6# 7%%
66
687"0###66
6%#%78"04
## %
*
6 78"07## 87"0 6 6# 6 4 ; 6# #7# #
#
6 % ?9D9 % 8 66
0/ 7D -7.3K O
/4///0;1-%:"14&
87"0,,#
%
6# 9+ % 4 ?9D9 % %%% -
72 #16.B 5>4?#
#
5> -0// %<1 #
# % 6# ,#% 9+
, #
# - 4 ./0/14 2% 5>7#
# % # ##% 78"0 0/ 7D -% :&14
6% 6,# 7%6
687"0 6#8 6# 678"0
##
2 A 6 %4 =## %6%
?9D9 62 6 # #
6# #
# 6 78"0 - 6 0/ 7D1 %6
#
#6%-7BBK E ///BB1-%:+14"6 6 %)>=
#0//K6
##9D3K+
-+1#G.3K)- ) 1-%:146,#7
,678"0 #8%68 %
%
#6#8 6 %[email protected]
14" 6
?9D9
##678"[email protected]
#
# 6
# # # -% 0/"14 %6# # %#,3#6 #6./#6%4"
6% 0/& % , 8 6 8 % [email protected]
6# % %% # % #
##
,%A
6 #,
#4 *, 6 # % *# % 6#%#
6#, %2#D3K
#
6 ,%# % # -0B9D "? -" ?1 ,93B:"?78"0
,%% M O/4///01-%0/0/+14
6 % 6 # . 6 0/ ## # 4, %[email protected]/
0//K6%)-) 1-%0/>14=#
6
78"0 8%% #
# # 6 %
4 ; 6# 6 6, ## % 9 , 6
6 3 BD3K#
##
#
% -3.3.
,9.:.
1-%00"00&14,#%6
6
6 # , % +90 % 6# 0043 K #
6
7
# # , % ,% 78"0 -% 00
00+14
6###6% ,,
8 # 7 6, # 7%%
66
6 78"0
%#,4
%,#
#6#
6
6-)##.//:1-5,###./0.1 -P4./0.14
6%-4./001-4./0.14#
##
,878"0#66
%
-1%4
# # GBB #,# 6 - 4
./0/14" 6%0."8 87"0
7
2 4 , F7) ,# GBB 8# %
,8 68"0
#,-..436#1%#==
-.94. 6#1 -% 0.&14 ; 8 6# 6% # :G7 , # -9/ 1 #
6 6 #,# %% 6 6 7#
% 4=
#,#,%#[email protected]<704:: 9/
6B#
42%##678"0
6
0/7: #
# 994DK #
6 6 [email protected]:J<7 049D3 9/1
#% 6 # % -% 0.14 ##66
# ##, ,, 6#
8%6%8 4GBB%6#626#
#6
7
#7
8"04 # % 6
, 6 GBB7
-GBB7
1 % , % 6 -% 0.+14 ; #, , 3 # # 6 6
#
,%%6
,678"0-6
6# ,6*,%% #-
4 ./0/14 ; ,# #, 6 0B 6 ./
%6# -% 0.>14 , 7
# # %,
#
-36./
14
687"0 %
78"0 #%6%##, 4
##%#6 70#87
"0
86%%4;6#87"0,2
6%,#
%%
6
6
4
; #6# # 6 87"0 2 % 6 #
% # %
6
6 % %%4 , #, # % # 2% 6
87"0
7
4
#,66
#
%%%#
7###, ,,4
; 6% %% # 6 66 #,
#%#%##6,6
687"0
6##
,
4
#, 626#6&6
%,
%4=##
#6
6 2 # % 6 ,, %%6&
##%6 %6
&4 8 =+0 %
2 - 16&-4.//:1#>) 6
6*&-.3K
99K-"# 4.//B14"% %,##-4
.//31-%4 .//31 ## %
# #
, 26#%66
# 2% % # -% 4 .//314 # 6
, 2 #% 6 # #
,
4 6# 8 6 87"0 # %# 6
% #6% % -%# =1 # -# ==<===1 # % 87"0
-#=514%8 6%#%6
#
6 ,,#6%87"08 ,#%
#
%
24 %
,687"0##
#6 -Q4.//D14%8 #
6 87"0 8 , 4 = #2% 6687"08 %6
##
, %
87"0 # ,# -R4.//D14=%% 6##
87"0 #
,#48 687"0#
,
# 6#, %%%%4
%% 2 6 , - # ./0/1 #
6%,-4.//D1 %
,687"0
6
8 7
##,4&,#,,
# #
7%%
687"04
,2 #6 6?5>
2
2#7#6
87"0 -(% 4 ./0014 &
# #
#% 6 5> 87"0 87"07## # % # # , 6
*,,65>#% )05>)7.4;,
8
### 7%%
%#
+0,
2# )0 -& 4 ./0/1 -; 4 .//31 -2 #
#C.//@1
87"0#
#
%66
6
84=##
%,##
6 )0 # 87"0 + % 6 # #
% #< 6 4 6 + #6
#
%7#
#4
##
##6, 66
#%) -
4./0/1%-?./0/12-#,./0.145
,6>)*7
-"2 ,4./091->#4./0914+
% 6 ,4 # 6 ,# 8
6 6
8 # # -
00888038880:1 6,% #66 6 )0 # 87
"0 # # % %4 =% 87"0 + % 6 G
%
-: 007031 %% 888 2 6 % #66 6
6 86
%6
4%%#,
6
#
#
#%#
6
, 6
4 , 6# + ,
6
8&0 7> 5>)707.79 >)7. =% S0 + 8# %6
8"0 +4 8
6 888 6 66
%% 4 ) *
#6% 6
6
4 # 6 87"0 #66
%%%
6
46%% #
2%
# , 66
#
4;#
#%6)0,
#-)
4 .//@1 - 4 ./0/14 # % 8 % # 7
6
6 + 6 8"0 #
2% *
6 # ## 6 )0 87"B4 66
#
-)
70 ,1 #
-"2#5>). 1%% 687"0 9"5>487"07# #
6
%
% #4,
86
9"
# % # -%
#1 # 5> 8
6
,,# 6%% -)22.//D14
6#% # , 6 78"0 # 6
%%,,4; #
#
#%
, %%,766
6%
)>=
->4.//:14;6##66 6
##-0//K?9D9#@/[email protected]
14 # #
6 6 % #
6
%4=
# ### #
6 % ## 6,
, #%%
64&,#78"0#
6#
%% , 4 2% #
%# 7#,#%
#
-GBB
- 4./0/14&# % ,6 87"08 % 6#78"0 # 64 #
%
2%
87"0 #
# 4 "## GBB 7
# 78"0 #
,,4 (% 6 6 % -) # # .//:1
#6# 87"0 % # % 4 2#%66#6
% 4
= # #6# 87"0 #%
# %
2 6
%4 ; 6# 7%%
, 6 ,,# 6 # %4 ## # 6 % 87"0 % # %# # 2% , *
4 # %##%
##%#%%# ,%
###
4
?9D9 -/@/G0:/01 # [email protected] % # 6 >" # " ,4 % 9DI 3 K '. +
T
#6# >% # -+> =&'1 # 0/ K 6 # 3 K 6
6 6 -1 -=&'1 0// ?< 0// H%< -%14
?5>-?
5>#1 ,##6-70..//1#
>70-
,
>#701 ,##6+>,'%7
% -= 6 &% 5 1 % ># #(-7..00/1 #6/4/.<>#
/4//B<> #
-
1/40%<
&
-
1 0 %< :/ U%<
#
0U%< 4 GBB 6
6 #
6 % 6 #2# ,## #7
# -?, 6 #% #% 14 6 # #7"#-
1.K6&.D -
1.
67%-
10K6
7 -%1#./%<6
>
-"1#- 14
### 6# # # -
14 # #% *
6
87"0V"=5=5=5"5="P()(-7
#
# 0.B/
([email protected] #% ? D/./G1 6# 78"04 # #)7:/K
#%6
#
4
# 6 % # 6 ? &8 -&0D/0G
<./@9<@/G<@/9<@/014
#
68"0
66
-3H
21#78####%0//K -.
6 03 1 0// K -. 6 03 1 :3 K :/ K
D/ K # -0 0/ ,1 % ,
# # 66 -0/ EG % W'D3:1 .8 0/ ,4 "6 2% -& J 3 K 1 6 ./ 787"0#-"
9.:G/70//1###
2% BI ,% # 6 0<0//4 " 8, % #-983&16
##-7
5
W=70///1#60<.//&60 4
# & -983 1 # #% 8# 2# 0 K .'. -% W0//:1 #% ./ 4
# # 6
6 % ,# % "& 8# -> 5
2 (7G0//14 +"& 6 ### -2 6
5
14 ### D/ K :/ K :3 K
0//K
## 6663
#%>2-%W/9:@:14
6 #%# % ,## %
,
6 %4)"8
#6
#
6 & %
# 6 4 )" 6 %# ==
"
# 6
-)3G../314 )" ,6
87"0 )" 8
# )% #% 6
C
-
)
=
4 >#814 )" # + =
-=,%1 # , # % % +" ) ( -6
%14F,,
-)F7)1
6# % * >8 8 -6 %1 % D3// ) ) -6 %1 6% 6
C 4
* 8"0 -4B9.9.:1 # *6 8"0 )"4 #%.H
+"4 "##"+ 6
%%*""+ -::::::/314
68"0)"*
% 66
#6%VX
-&81E
-8"01Y
-"+1 )" * E .Z-X
-& 8"0114 >
, # .Z-X
-"
==8"014
[" #\ -
" )
2 .//@1 #
###
6
"
#
- V<<
%7
#4
44%,<
%<
%.4A M=?"14)"#%8 6
# "668?099" #4
, 6
B:: 6( ,,4
[)##\ -#,4.//:1#->6"6687
?099]].
1
###
6
"
- V<<
%4
44%,<
%<2 4
M=?"16..G&#
[email protected] 4 ) # )" # % >8 6
-"66814=
& 6#%#,680
8 66 % 80 [email protected]]] 4 & 8 , # 6 8 %# [%
80\ % # , 8 # [80\% 4"( 7,, 6#%%7
2%6
6,,#66
% - #
14
! "
7%# #
-7+1 # ,% #
6
6,)0#N"0####
+' -0.7#777%
797 1 # 4 )'" 6
2% -, B434B1 -5 + 4 .//31 - .//@1 #4 # ## #
# ")==6
76#
,.40-2#2.//B1-24.//D1-
4.//@14=%
# % 5+ 6 - 4 0::G1
- V<<424
4#<)
<,#<14 " ## # 6 #
,## #04
#
$ %&
" 7# # 6 # " 6
&# #7## 6
#64&" (.3# [email protected] #
#%6
# %%*
6##66+6#
.3#[email protected]%6#
4+6&0/0-
71>4
% # #
# 7
# :G7 >" 6# , #
# -& # &, ./0.14
#*
### -014
"
&#% 8 6# 6
&
./// -&
=
41 ./ I4 ,# # %
6
# -:/// 1 ,# 3 % ## 7
% ##
#6
4&6 ,#A
#
6.3/U%<./#
- B431663U<
## 6
# # #4 ?
# % 2# A
% 0 4 6 #7 # # 8"0 # # # ## 66 % 0/ >> D4B03//4//3K-,<,16
./#9+"'
#4#7)0 ##6
6 &
,# ## 6 #66 % #
A
# 6 6 3 U<4 &2 6
# 6 2%# 4
=A
6 9/H 0 + # % 6
#%
8 4;##2
6 #7 #
4
= , 6 # % -97-B3 7+7. 717.37#
#1 6 #% 6
C -% [email protected] ?"14 ' # ## 3D/ % >=" # ->@//&[email protected]#
###60////
:G #
% #
-%%60/ [email protected]/7G1
#%,
% -+ %% 6 /4D .H D./ H14 6 ,#6.B
#,#6#0//H6 #
6##-0<3/&16
2-3%<1###
6B
4"6
# -0//H1###
6#% #3D/4
!
"%%%6?9D9#>
#%%%# *
, #
# - 4 ./0/14 03 9/ %%% # # % , ,# ./ H 6 2 -% 6 79.GG1 # ./ H 6 [email protected]/H6&J./H0////?%[email protected]"6B3
% . 6 # % 5> -0// %< /:B
1 78"0 " 0/7D ### #4 %%% # 6 03 9DI4 F6
# # # #6%%%
%,6%%%
'!
>8 6#
#%#6#?6"
->[email protected]#> +
, ,6%
-)6
"<33<G.</.<0914 ,# 6# # # 4 " 6
#%'.4"
2 #
66
4 %6 #
#A
%0/ G
626 %7
6)=#
-, =
1##,#
%4
6 # 8% 8 6# 8%
% 9 K 6 # # # . K 6 %6
24
20%# #
626 -0//H0/ G
[email protected]= #6+-D.H16
% 78"00/ 7D#,
# #% D ./ # -6 ?9D9 # [email protected]
,1 #,60//94"#6 6
##
# 6%%-?9D91 # 6%
[email protected]
[email protected]
%% 6#%
%';&[email protected]/,,=%%,3##6
6
4
GBB
8 %6
#,5 # , 87"0 # # %6 # #, 4 ;
6# %6%60/ G
626./#
7
# 6 0 78"0 0/7D 4 "6 3 # 6
6 #, % ## % %' -&#1 %
#8
[email protected]/<G./ ,14
"
!
6 *# %#
0/H
2 4
# 6 # & 0N3 68# " B K #% ./ #
# /4/. K 2% -& J3 K 1 #% 0 -)14 # # ,% BI 2%
4;##
%%+90->"70&+7%
V33
/.DB10<3/9- /G73D/10<.//87"0-)L+"&G39G10<3/4"6%
-9631
##-#27#27
2=
D0070G3703.D037BD3703/##0<0///6
21###
6:/4"6%&
#
+"= -BC G7##7.7 # 0<9//// 1 6 0/ 4 , 6#
%#% #-,
%
7
2
[email protected]:14
#6B#6
##[email protected]/I'
724 72 2 0/ H 2 4 # 6##
% 6
2 - "&3:..1 # # %% 87"0 -)L+
"&G39G10<3/4
7
68# " B K #% 0 # 2% ###
#%0
()
, %% % % - >G.31 ?5> ##0////<6 :G7 4 6#% 6
C
"7%%
66
*6# % 6
4
%%
*)+
75>)7. -00D31 #
>=" 27&# 6 %%
% # , 6 # 5>)7.4 ?5> ## 6G7 #63/////
.6
##,#,%4
#,
-+D.
H178"0 # 60 0/7D
#5>0G3
0// %< #% 0/ 4 ,%6. # #% 6
C
4
%
(%
" 6# % % %%4 "6 B # 9DI ##6##4"%
6##B#6# 6
,%
%%
,4), 6#./H5>0G3-./H%<1
6
5>0G3 -./ H%<1 J 78"0 -0/7D14 "6 .B 7 % 2 6 *6
6 , %4 # #% 6# %6 #,# %M %
6##
#4
"
,-
#6 0#87"0#+2
6 '2 &
4 = 6 ?9D9 # %
, 6 .B 6 68 B K 6## 6 0/ 4 #6&J/4.K#%0/4#
#,%BI87"0-)L+"&G39G10<3/# 0-
%%
" # -&%# 4 .//01 -&%# 4 .//B14 8 #
#%6
^
4
6 78"0 ) %% 6# 7
=")
"
, " ( 6*=
4-&(0.314?9D9
## G7 #63// ///
. 6
# #
,# ,%4 # ,
-+ D. H1 78"0 #600/7D6
9"-)L+)
9" 0.3/797/.31 #% 9/ 0// %<4 %
#
#%6
^
4 .
?9D9
###6G/////
G7 #
,#,%4&6 8
#0/ 7D67
8"05
-+D./H1#%04# 9"
0//%<9/5>0//%<#%0/4"6 #& # & J /4. K # -)
[email protected]//01#36,#4= # 7 87"0 # -)L+ "&G39G1 H" &# - 09/7/D070/01 # % 7
- 09/7/B.7D/014 % # #% 6
^ 4
,# @ K +<"> % # 6# -;142#
2%-&<0K<3K21
60)4#-)7 72)72%%WB/G/
# W:.D. ,1 # 7 _ - %% W.0BB1 #
,% BI4 "6 , -9 3 &< 0 K1 #
#-77)>
W":9B5#77)>
WN":901 # 0 ) &<0 K <3 K 24 , 6# % ,#7# # 8# 8 -"
W)0/301 #% 6
4 =% 6 7 *###2>>'> -%&=%%?(14
/%
!
# % 6
# -)" % 1 6
%6#,#
# %4%:G7
#69/
%3/H6
##%B#4"6
# 6% # % 6 4#6
## #[email protected]
4
6%
##,#%6 #B 6
#%,4
/
6#%;-6 O9/1*
-6 *, #1 % # 6 -?"14 7, %, 6%%##,6O/4/3
##
%6
4
#6,
2#% #6-?"14"6
# # 8 6# 6 , - 6 %
%%5>)7. )
""14
"# (4+4&(4"4&
2444&%44
&4;42)4&4#4+4-.//B14=
#
6>),===
%%
%#
#,6 %
%6
44
4>8 44
D//YD/D4
"2 ,"4P4+)4>#44>#44;+4>4(4
#+4>4-./0914"
#
6>
4
33DY3G:4
&%
4;4(46)4=%44#+44-.//:14"
9"
%% %# 4'
%939DY933/4
&%#+454(44+644
"4;4&44
&4#4-.//014 9"7,
#%6
70G3
#%# 6 %
6
#
44
4'6644
4
4999.Y99B04
&%#+44+444)4"+4
& 44 # 4 -.//B14 +66 " 2 , #%
9"7#
# 6 %
444
4
D..YD904
&44&44"4#(44-./0/14 70%
7#,#%6
%%
4&
44
.:YB/4
&#>45"4)#&4#5
,"44-./0.14%6
7
%
%44&
4
4>#[email protected]
&,)4=#474,;4(4#4&4-./0014%
%V
24
)4B/33YB/G/4
&6#744)44##"4(4-./0.14)
#
6
%% V
#6%444'
4'6644
"4
44'
4
B/.GYB/9B4
&4#4-.//B145
#%6
-5>1
70C#
4"="
4
4=4
#4.3DY.G94
&4;4#4>"4R 24%
(4>4"#)4
4+
4#44-./0/14+66 866
72%
44
)4'6644"4"
4
)[email protected]
")
2-.//@14 ,%
#6%%#
40/G0Y0/[email protected]
4P4P474
()44&+4(4(44##44-./0.14
"
#
%%%6
4 3..Y3.G4
4#
#+4-./0/14878
,,#
>&
%%4"#4%4.::Y90.4
+4;4F4%(474%4,;4)24
#+44
4"44-.//@14"
, 6%%,
%7# #%,
,,% 09/
,%4
)400G.Y00G:4
5+ +4#>4&4642"4>4#&#444
-.//314)'"V668#644 440D/[email protected]
+%4;N4)
444%"4#"4-.///14
>8 #%6 70
4=44
4=4
[email protected]:.4
>>4"44&%4
44%+4#)4+
4
"
24444-.//:14 ,
#
V,#)>=%#-,04014>44
'864>%40::/[email protected]
.BD4
># 44 + )4 "4;4 "2 , "4 (,
>4 % P4 44 P4+4>4;+4>44-./09146
%
,6>
43B9Y33G4
2P4##C44-.//@14 70
66%%
6
70
,6# %
,442
4
&49/.Y90/4
4"4PN4#4+#44&4)6#44
#"&-./0/14,,6 #%#
%####
#?#4
4
)4'6644"4"
4
)4.BB9Y.BB:4
244+4))4;F4&2,44#4&2
4
;4244-./0.14"
5>75>).7 70%%
%72
,#%44>8 4#43/DY3./4
4#,(4-./0.14
7
#%)(
,#
6#4&
4& 4"
::3Y0//34
%4>4+"4744474#4;4(
4464"4;444-.//314%
%#
66#%44>%44#4
::DY0//94
%"4&42)42+4P%+4;%44)4#
"# (4-.//314%
66
6 #%6
#>),===
%6 44
)4'6644"4"
4
)4
0BG.Y0BGG4
#>44-.//014%V%
##44),44
0./Y0.:4
4(4#&
24-./0.148
%V 6,
,%6 %#
%%
#
6
4446
[email protected]/34
44+474(4!4&%#+4#%4-./0/14
%7 %#
%#
7
V
`"#4%4909Y9.B4
;4+2"4#
(4-0::G145+V,
#
444
[email protected]@4
)4(4#>4+#+446644"44#&
44
-.//D14"%%44),4
4G0/YG..4
(64&4548&444'4
44
'
,474#(7 #4-./0/14;6# #`"#4%[email protected]
(%&4)
45,2"4('4#6#4-./001487"B
%#%%
65>#
%%4 &# [email protected]:G4
>4#,(4-./0/14)
2#V
#
##%
4"#4%4.B:Y.3B4
4&a
2#44&4)4#!+4=
(4244#
544-.//314
%6
6>) 6
#>),===
,#
%444#4&44
:0DY:.G4
#,4R2474(,P444"4#&(4-.//:14
)#V % ##
%%,
44
)4)03DY0GD4
4"4#&#54-./0/147
%
-)1
#V" #%66#4"#4%4
[email protected]
2474#2"4>4-.//B14
,68% 6
#4& [email protected]:BY9://4
244)#44P6,4+44##5"44-.//D14
")==6
6#V
%##6
4444&
[email protected]@.B4
4>44+44#544#4-.//@14
6 ##
V
#
%# A
44 440DB/Y0D3.4
Q4;44"4
444'4> =4?4&Q
4
4 &Q
4;4'6644-.//D14"
68%#
6
9" 4=44
4=4
.B.0Y.B994
4)4
4)4(
>4"4#44
4!44-./0/14 #7#6
6#
6 70%%,,4'
%[email protected]:.4
2444"4)4-./0914%#V ,%
#6
%%#
43/G4
#"4+4+ 4#;4P4-.//:14"%%
6%7%#
%44),44G0/YG./4
4#=44-./0/14%%V%#,44
'
409.GB04
'%24#(4-.//314> #%#%6%4"
4-&41:9Y0/@4
'# 4 2% 4 4 2 4 " P4 % "4 (A 4 P2
4?P4#24-.//B14',8 6 0-)01%
# %%4"
)43BDY33.4
)4)
75444&664
4
4
4+)4#
44-./0014>8 6
2
+099
%#,6 %4
0G.Y0DB4
#C44#2P4-./0.14 6
,,#%#4'
%
:.0Y:9:4
)#+4"44(4&4+A#"4%4 44
#)4>4#4>4.#4;4(2 2444-./0014",6
5><5>)7%# 6
%444 4
4B0BYB.D4
)&4'"44#Q
"4;4-.///148< 8# 8%#
% 9"4
4+,4
:3Y0/B4
)#2=4##;444-./0/14%# 6
V%%
%4
40Y0/4
)44##44-.//:14
%
86
#%4
0GD/Y0GD94
)22)4-.//D145
#%6
-5>1%%
%44),4'
440D:Y.094
)44+%7
4"+4!44#&%#+4
-.//@14#
%
6
6 704
4&4GBGYG3B4
4P44=#"4664+
4>4&
&42(4%7N(44-.//:14=
##%0
#09.
%
2%444'
4'6644"4
4
4'
4B03/YB03B4
%,"4&4-./0/14 %%%%#
4"#4%4.33Y.GD4
224N4#=4-./0914"# 4
00:.Y00:@4
#*,"4R"452>4#%4b#%'4(+4
(4#474#%?4+A244-./0914 6
# #"70
#S7#
#
,4'
%
9G/GY9G034
24"424;%442P4()44A
4#44-0:::1487 70
866
7
9"
43:YG:4
%4"%44R4%4=4%4#"4;%
44#4444-0:::148%66
6
# # =7
# ,4 [email protected]/4
54R45)44#=445 =44
R4#
4-./0.14>#
#6 66
#
,#8 76 4'9:3B94
44
4#"4-.//B14
,6 87"0
%#)
44&44990::Y99./34
?44-./0/14
6#
%
%%4"#4%[email protected]
5,#4>4##44-./0.14
V
#,,%
[email protected]
;4%4+4#4-./0914)
#
,
%%#%%
444=,4
90:/Y9.//4
;+44)44+
444444>4+##4
%#4;4"45 44-.//314=
6 #%%6
70# 6
,66%
6
7.44&4409B3DY09BGB4
PP4)4#>)44-./0.146
6#
44&
4>>#[email protected]
RN4 4NF4#P4-.//D14c>8 68"0%
# %%# 6d4R%;%;(
RR444%[email protected]
$
$V
8"0%# %
26%,4
-"1 8"0 % 8 ,, 6 & 4 -"1 "
# -&1 )# ( , #
% ,, 6 4 #
6# % # , 6 8 4 %72 # %6
6 ,, #66
4-1 ) , % %8 %68"0#66% 4&
28
% %6
6 V B/ H4 -+1 F6
6 87"0
8 #% %# 6 " =E "
%# = " ==E
"
%#=="
%#===&E47,##
7O/4/3MO/4//0MO/4///04->1)7*)8 687"[email protected]
& 487"08 #8 6%#==="
-==1 4
$%&
% #
+' 6
6 )0 #
8"0 + 4 % 8 #
6
6 4 8 # -2 6
%
#1 ,% #
24 # *
#
#
/43O#O/4G#*
#
% #
-# e 0 14 % # % * # ##
/4GO#O/4D/[email protected]/4:14
V
#%.)0#08"0+4-"1#+0)07
. 0M -&1 # +. )07+9 8"0M -1 #+0 )07
+9 8"04 ##V #% 0 )0 # . 8"0 +4 -+1
# +0 )07+. 8"0M ->1 # +0 )07+9 8"0M
-1 # +. 8"07+9 8"04 &V -1 " 6 + 8
%#
6
9)0#98"0
+#+'#%%D.H4
$'V
9+ # 6 8"0<)0 4( 6
% # # # -%.1%%# # #-
P"#
214)0
6%##48"06%#%4-"16.
)0##08"0#-&160)0#.8"0
#4
$ (V
# 6 87"0 *
4
-"1 &
"# 7# #% , 7 #678"0#6 ,
7
4
6 # & %
# , -"?14 R *
, 6 # # > %, 6
#4 0V 0M8"0"."9"BV8"0"."9#"B4
-&1 &
"# 7# #% %, #678"048&0V8&0M
>V %6
M5>)7
0 . 9V 5
># )
0 . # 9M V "M
>).V> #
)
7.M=S0V=%S0*
6#66
-16
-&
1*6678"0
# 2% #4 =
# -)?14+66*
#V8"0V8"0M 0V 0M5>).V5
>#
)
.4
$)V
78"0 #
8 "0 4 -"1 +2 % 78"0-0/7D1#
68"07)0
?9D9
4
O/4/34-&1= 68"0?9D9#5
-+
D. H1 9" -0// %<1 9" J 78"0 -0/7D14 6 V , 6
8"04)% V,6 04-1= 687"0?9D9
#5
-+D.H15>-0//%<15>J78"0-0/7D14
6 V,6 04)% V,687"B4
$*&
78"0 #
#
%% %%# 9" # 5>4
-"178"0 )"
,#
#0//%<6 9"?9D9
4O/4//04-&1 #"2"2##;&
?9D9#,
-+D.H1 9"-0//%<1 9"J7
8"0 -0/7D14 *6
6 K 7"2<"2 #66 #4
O /4///04 -1 78"0 #
5>)7. #
# 5>
-0//%<1?5>
4O/4/3O/4//04
$+&
78"0 #
%,4-"1
% %
8 687"0,
72
%4
VB/
H4-&1+678"0%%
66
630/7D
%% ?5> %4 O /4//04 -1 = #
, , 678"0?5>%#
#5>-0//%<1#
N%
4 6 #66 #
,4 O
/4///04 -+1 + 6 6 78"0 -0/7D1 2 5>
-0//%<1 #
# % 6 > %%% %% 9+ 4 O
/4/3O/4//04
$,&
78"0 #
%% ,,4 -"1 % % 8 687"0#,6
2
4
V
B/H4 -&1 % # # #% 6 , 6# 6
,6.B
5>-0//%<15>J78"0-0/7D14
-1 6 # , " *6# # # 8
24O/4/34
$-&
78"0%6?9D9
4 -"1+6#7# #
7 6, 66
6 78"0 6 .B % ?9D94
O /4///04 -&1 + 6 6 78"0 -0/7D1 2 %6?9D9#
#5>-0//%<16
%%%%%9+
# 84 O /4/3 O /4//04 -1 ;6 % % % ,6 #,##-% [email protected] #
,%, ### % -#2E0/1D<04
0//K6# ##9D3K##G.3
K 4 -+1&82 66%6?9D94O
/4//04
$.&
78"0 % [email protected] 4 -"1 + 6 #7
# # 7 6, 66
6 78"0 6 .B % [email protected]/4//0O/4///04-&1 ) , % % 2
6%,./#8 % 4-1# %
,6
%[email protected]
14>
#,##,6
6 # 6 *4 # A
6 ,
-D.
H1#78"0-0/7D19 24
*#,
3 # -?"V " ?14 -+1 6 # % , %6
#66
# % 78"0 -0/7D14O /4///0 -V #4 ->1 ;6 % % % , 6
#,##-%E0/1
#,%,
#
## % -#2E0/14#@/K6#
## -e9/K#
14
$&
78"0 6 # %% ,,4 -"1 ) % 6 9 % [email protected] 4 -&1 &8 2 6
6,#8 #6#69 ,
/40f64
O/4/34 -1) % 6+90%
[email protected]
4-+1&82% 6
%*6
6K+90 Hf64
O/4/34
$%
78"0 7# # %4-"1 ) ,
% 6 -%1 8"0 -#1 # % -1 % GBB % 4 -&1 )7*) 8 6 87"0 " ==V
"
==#GBB4-1+6#
6 6
8"70 -0/7D1 # # # ,
-D.H1 E ////34 -+1
) , % % % 6 3 #4 &
2 %%# ,
-D.H1 ## M %%# 8"0 -0/7D1 ##
4->1F6 6#
GBB
E///D34
/
/
)0#8"0+*
2 6 , *
%, ? #- V<<4 4%<14 %6##A#
##%[email protected]
#*
##% 6#
#4
26
+*
,7#[email protected]
6####
#
##
4
-. # 81 #4 ' # 6 9
+
#%.)0+#08"0+
#
#69+
#%0)0#.8"04#
#9)0#98"0
4
+ # # % *# #% +' -0.7#7
77%
797 1 6 7*# +'
2 6 ")== - V<<#4
4%4<
%<14 N P R
#[email protected]:4.:[email protected] ,#
#0/[email protected] ##
03BG/
4
## 8%
-R814>
###88
#%#6888 66 ,
4 +% # 6 # # - 6 # #% 1 ,# 6 6 # 4 ; #
+ #G6
4
>
6 % ##*#6 6%+
9//(4 #%
60
# # # # % % &#
%-&#40:@B14 #%7 -# #
%
## #0
%
6/43 #
6B4380/737014" 6/4/B/ #6
#
4##
6#/4:
#04.#/4/#04. ,4
# #60H
*6 +'4
# 6 #66 # #% 6 ## # 66
% , 6 #4 #%%%,#40-.)0+J0
8"0+1.-0)0J.8"0+1#9-89
)0+J98"0+1 6#,[email protected]/H#D.H ,4
/
" 6#% ,##
2%-5+ 4
.//31 - 4 .//@14 =78 #
-#
6 6 8 2 # 78 #
- #
8
21 #4 " # 6 # #
/434% #6
%,%#
2#
6# 48786
8
#6
4
= ## )+ -) * +,1 6%##%
##6 #6
#% # 6 # -)+ ,
/4914
/
/0
*
6 #,#&"4
/
!0
-" !
"" #$"$%&'"!" &(!)*+# -&1
% % 2 6 87"0 8 ,
72 #4&
2#%%#,4
VB/H
$
'
'
,
:
+...
%
B
5
$
'
+..
%
A
$
'
@
%
$
'
.
%
.
/
+3.
$
'
%
-
.
$
-3.
'
%
@...
$
/...
%
%#
+
-...
'
A.
K
.3...A
$
1 # + 1 5 * 8
1#+
[email protected];>
1 2
=#6 " "
> =6
1#
+
@
.
J 1#+
=K-A.>
%
+
/
+
K
+
K
+
""
+
.
'
"
K
@
+...
$
K
+..
%
"
+3A
"
"
.
#
.
#
#
1
1 # + 1 = 5 2# 5 * ">
# + 1 = * L *
J 1#+
=K;@>
8
1#+
=K;/>
K
[email protected]+
A.
-...
/...
5
5
+/
+-
++
+.
A
@
/
-
+
@...
"81
=*>
'+
!+0'-
!+
"81
=*>
'-
!+0'/
1#+
'/
1#+
'+
!+
M-,
-:
-B
-A
%[email protected]
-/
--
#-+
%-.
+;
+,
+:
%+B
+A
#[email protected]
+/
'+-
#++
"+.
";
,
":
B
"A
@
#/
-
+
"81
=*>
'+
!+0'/
1#+
'/
1#+
-,
#-:
"-B
-A
[email protected]
#-/
--
"-+
-.
+;
+,
+:
+B
%+A
%[email protected]
%+/
%+-
%++
"+.
%;
,
":
#B
A
@
/
-
+
-,
#-:
"-B
-A
[email protected]
#-/
--
"-+
-.
+;
+,
+:
+B
%+A
%[email protected]
%+/
%+-
%++
"+.
%;
,
":
#B
A
@
/
-
+
M- ,
- :
- B
- A
%- @
- /
- # - +
%- .
+ ;
+ ,
+ :
% + B
+ A
# + @
+ /
'+ #+ +
"+ . "; , " :
B
" A
@ # /
+
M- ,
- :
- B
- A
%- @
- /
- # - +
% - .
+ ;
+ ,
+ :
% + B
+ A
# + @
+ /
'+ #+ +
"+ .
"; , " :
B
" A
@ # /
+
'-
!+
'+
!+
M- ,
- :
- B
- A
%- @
- /
- - # - + %- .
+ ; + , + : % + B + A
# + @ + /
' + - #+ +
"+ . "; , " :
B
" A
@ # /
+
'-
!+
"81
=*>
'+
!+0'/
1#+
"81
=*>
'+
!+0'-
1#+
'/
1#+
'-
1#+
"81
=*>
'-
1#+0'/
1#+
'-
1#+
M-,
#-:
"-B
-A
[email protected]
#-/
--
"-+
-.
+;
+,
+:
+B
%+A
%[email protected]
%+/
%+-
%++
"+.
%;
,
":
#B
A
@
/
-
+
M-,
#-:
"-B
-A
[email protected]
#-/
--
"-+
-.
+;
+,
+:
+B
%+A
%[email protected]
%+/
%+-
%++
"+.
%;
,
":
#B
A
@
/
-
+
M-,
#-:
"-B
-A
[email protected]
#-/
--
"-+
-.
+;
+,
+:
+B
%+A
%[email protected]
%+/
%+-
%++
"+.
%;
,
":
#B
A
@
/
-
+
'+
!+
M- ,
# - :
"- B - A
- @
# - /
- "- + - .
+ ;
+ ,
+ :
+ B
% + A
% + @
% + /
% + % + +
"+ . % ;
,
" :
# B
A
@
/
+
M- ,
- :
- B
- A
%- @
- /
- # - +
%- .
+ ;
+ ,
+ :
% + B
+ A
# + @
+ /
'+ #+ +
"+ . "; , " :
" A
@ # /
+
M- ,
- :
- B
- A
%- @
- /
- # - +
%- .
+ ;
+ ,
+ :
% + B
+ A
# + @
+ /
'+ #+ +
"+ . "; , " :
B
" A
@ # /
+
'+
!+
'/
1
#+
5*
<
'
/
'
!+ E / '
1#+
'/
'B
'A
='+0'-0'@>0='A0'/>
* F
.
,
.
B
.
3;
.
.
.
3/
3B
'+
'+0'-0'@
@
'+0'-
.
-
'-
3.
'B
='+0'-0'@>0='A0'/>0'B
.
'A0'B0'/
'A0'/
'A0'B
'@
!+0!+1#+
%M
'
##
!+01#+01#+
%M
'
%
!
6
1
+
#
0-
+
.
+..
,.
B.
@.
-.
*
+
+
+
#
0
++
0
8
6
6
-
#
+
5
$
6
%
%
%
1
'
%
*
0
0
+
+
?
0
0
0
+
0
0
0
#
#
1
1
1
#
#
#
1
1
1
#
+
5
#
1
?
1
0/
0-
0+
1
1
1
#
#
#
+
+
+
+
#
5
#
1
1
*
?
0
0
0
0
*
!
?
0
+
0
0
' 0
= 1 #
+ = $ >
0 5 = # > $ 0 5 1
1
1
1
+
#
#
#
/
-
+
5
#
$ $ 0 0 5 5 = # > -..
+..
-..
+..
#
+
+.
1
.
0
'
! *
'01
#+
-.
#" 1#+
0
!+
! * <
! + 0 1 # + + 0 1 # +
< ! !! = >D > + +
= D
11 ## + +
= D= >D > [email protected]
+-.
+..
+..
,.
,.
B.
B.
*/#
+..
A.
*/#
*/#
E
'01
-A.
-..
+A.
+..
A.
.
%6
%6
E
'01#+
%6
%6
E
'01#+
*
/#
*
/#
E
'01#+
11 #
# @@
=
D= D
>
>
! ! + =D >
+ = D >
*/#
E
'01
*
/#
*
/#
E
'01#+
.
%6
%6
E
'01#+
%6
%6
E
'01#+
+..
1
,.
B.
#
'
E
*
#
*
/
'
0
/
1
#
0
+
5 D
# # 5 =D >
"
#
"
$%&%
= D > 0 # N 2 # N 0
=#
D N = D > !
+..
A.
.
*/#
*/#
E
'0
1#+
*/#
*/#
E
'0
1#+
% -6 0
0 - 5 % 6
A.
.
+..
%6
%6
E
'01#+
%6
%6
E
'0
1#+
1
#+
" " >
= D > = D
'
(
&
+..
A.
.
.3,
= + 2 >
>
= + 2
,
%6
%6
E
'01#+
B
O
.3...+
@
-
.
.
+
-
/
@
A
*
=>
B
*
=>
:
,
;
+.
.3B
[email protected]
.3-
.3.
'01#+
'01#+
+..
%6
%6
E
'01#+
J
= D >
1 1 J * =D >
$
%6
%6 E '0
1#+
,.
B.
@.
-.
.
%6
%6
E
'01#+
%6
%6
E
'0
1#+
#" 10#+
)*+$
)*
<< = D >
! !
** +A.
+..
A.
%6
%6
%6
E
'01
#+
%6
E
'01#+
'
,.
B.
.
+3.+. 0 ;
+3.+.
+3.+.
+3.+.
'01#+
='>
0,
0:
0B
'01#+
='>
)*+$
)*
J *
J = D
>
= D >
+..
+..
B.
@.
-.
@..
/..
+..
J
0A.
!"#$%
0+..
6 *
.
%6
%6
E
'01#+
%6
%6
E
'0
1#+
A.
,.
.
6 * J = >
* * =D >
* D D
< <
.3+A
.3+.
.3.A
.3..
'01
#+
'01#+
+..
,
,.
'
B.
.
+3.+. 0 ;
+3.+. 0 ,
+3.+. 0 :
+3.+. 0 B
='>
'01#+
='>
$
-.
&%
'()
+A
+.
A
.
.
A
+.
+A
+A
+.
A
-.
(A2(.
(+.2(.
(+A2(.
(-.2(.
-.
.
D
* * * = D > % J * ( - . 2( . D <
** % J J D
=#
>
6 = #
J >
( - . 2
'01#+
'01#+
+...
;..
,..
@..
*
!"#$%
/..
-..
+..
.
0+..
#" 8/
<< 1 1 = 8 / >
'
$
,
B
@
#" /+
D D / + F * P
<
* / + F * P '
$
B
@
'01#+
'01#+
'01#+
'01#+
$+ %,
D <
* +
$
1 # + 1 < * = D1 #
>
+ 1 =< % # 8 >
!2
#"
.
!*
.
.
!*
$
@.
&%
10#+2
#"
-A
-.
-
+
#
""
#
""
%
[email protected]@
[email protected]@
+..
A.
'01#+
+.0;'
'01#+
,.
B.
-.
'()
'01#+
'
!"#$"#
%&'(&(((((%%%%'&''%&)*+*
,-"!.,+/
&%& &&%('%%('(''%)+*+
"#
."#
/
%&'&((%%%&&'&&'%&)*+*
"#."#/
%(%(((%%%%& '%')*+*
"# ."#/
%&'&'((%%&&&''%&)*+*
"#."#/
0'(%('( %%%('&&&'%)++*
, (%&(''& %%%%%(%1%**+
'2(+!
,%2%& % ' %1%%% %&+**
'2(+!
&&&%'( '&1%%%'&&%+ '*+*
'2(+!
2&'&%'( ('&'1'%%%%&,++*
(
&2& %&&('('&( &%%&)(&++*
32+
&&&''(&%%'''%(''(&%&*++
&!./
&&&'(''(&'%&(%%%%&1*%%*+
"45657"
2476-75
2
2
"75
"4568
/
00
4.9;.$#&
4
'
)
;94:9
B'" H ' N) ' !>OM/-% + '' ' '
)* - '
+ ' ' '
'''''
)
'+'
-
H
''
)
''+
D
'+
'
-
+'''+4:9
),##
. 8 " '
' , '
+ ) '
' )
'+ *' !
" % -" (' ) ,
' !
" '* ) '
* , " '
' '+(
% '+ ) '
) )
' 5 , H ' ) '
))
+)
')
* '* '3' ' '
(
)
' ) ' , " )(
)
))
'')-3
'
'
'
'
!H,0
% ) +)
'
4:9 *' ' ' IJ
'
)!I;J%
g
,
S
)!6
" ##%" !5 " #% +
'
''+ 4:9 ;94:9 ' ' '
'
B " ) '+ I J ' ) ' '"'
4:9'*'
0A
S ) !>8
" ##%" !/' " ##&% )
3
',
*
'''+
/" '
' ' '* ' ' '
)* * )' )* ( ' ( '+ 46 ) $ ' H
)
'
'[email protected]
0 .Q )
' )
9 " '
" '
'
)
0#.
-" '
, * + M/65"M/65:
4:9"'+
+' / " '3' '
' + M/65:" M/[email protected] M/65: !=
" #% + ' M/65 4:9 !9 " ##$% '
* # . M/65:" 0 . M/65 @" ' M/65:#.'
4:9-
+
+,
#'7L
4:9#'7L
M/65
?&##,&###
;94:9
, #$ !) , "& _7L% 4
)
'
;94:9H,#? '*
'
'*'/"
'
)'
'
'
) '* 4
)
'
!="##%
'*
;94:9
'*)
' (
M/65: M/65 >OM/-'');94:9,+
M/65: - ) ' (
;($&''
!>
') " ##%" !K " ##0% B ' ;94:9 )
M/65:
'' (
;(#& ;(#&A )
)
M/65:!C"AAA%-'
(
M/65:*<
'
;94:9)
'''+4:9
A#
'3
'
'
'4:9
)
M/65:'*
M/65
+
4:9M/65:
-" * [email protected];> =
'
( '''+4:9M/65:@"
+)
' 4:97M/65:"
'+
'**
" ) ' ; '
*
'
'
"
' '*
4.9;. &$# % =
' ) + ' '
'
'
'
6***6 / " ;94:9 ' ( '
6***6***6 ' )" '
) '
''+4:9/)";94:9'
8 ) ' ''+ 4:9 - * '
* ''+ !0# . '
%
-
'
4'
)'
'
6***6
'
4:9-
) * ' 4:94:9 , ''+ !- " AA0% ' " '
''+ 9*@" ) 4:9" + )' ) ' ; 4:9 -"
)
+)
))
';
\M/65:"*
4:9BH
) '
''+ (
@ '
' '
6***6 !:
"##0%@"
'''+4:9
'' ,
'
6***6"'
A
' '
H
S ' )'
(' ' +
'
'
''+ 4:9 - ) + '*
'
+
' ' ''+ - )
'H)
+
'
) (4.9;.C
)
'
)
+
'
;94:9 '
'' + '
''+ 4:9 )
" BB
!9-4:9% ) -' ' ''+ ) *''
6***6
B!9-4:9%
)
4'
'''
6***6
'"
BBB!9-4:9%
*'
6***6++
'
!)
'O$%
'
'
M/65+
'3'
)9-4:9)'
- * '
'
''+ 4:9 ' -'" ) ' '
6***6 '
'
4'
3
*'
'
-
'
'*
B ) (
) * ''
4:9
)
' ) 4:9" 4:9" M/65: 9*@ - S'
* '
''+ H, '
'
-'>'
'
'
'
4'
'
>)
>!/"##A%
A
'*'
" 9-4:9 9-
4:9
B
*,
* 6:@MT
!6 @) >(
(% ) (
+ "$?
9-4:9
'+,#"&&"#?
9-4:9
9-4:9)'-)(
+9-4:9'++,
!"$#% @" +
+
+
+
' B ' ,
!
'':
'%
'
+
+
/ " H, ' ( +
+
;94:9 , ' , +
+ +
) !4 " ##%
3' + ) ' +
+)
/ " " + '
B
'
6***6'
''
'
) * '
+
9"'+
+H
'
[email protected];> /)"(('
=
'
5:/; ' '
',
"
('
'
!'
+'
%'+'
' ''+ ' S
'
'
A
* 4.9;.$#
4
')
'-
)
;94:9 '
+
')*
'
' ! -?% ' !O$6%
*' ' 4:9 W ) ( '
O06";94:9'
,' ;; ' ( '
''(
''*'
((
'*/)";;'
)+*'
)
'
'
' )' + - '
S4:9
''-
' ) M/65: M/65 @" ' '
!)
&.%'
(
M/65:!
&.%
+)
@"'
*
+)))
'
'
'
")+
'
+
)
'' 565" 965" ;65
+"965
>65 '
)
'
!K"
##&%" ! " #%" !6L 9
''" ##0%" != " ##%"
! "##0%'
+
+
++
;
';94:9!
'+
(
'% + '
- ) + ))
'
' *
''
'*
]+
)
' '
? . * S # . , ;'
8
' ) O$6 O ++
'
'
#.
, + ' (
L + -" A
(
'+'*
)
,
0 4.9;.$%#
@ )
'" ;94:9 ' + !#$ "&_7L%+
'
+
* ;94:9 $ ' (
'' *' ( ' !>/96% "
'
d!"0"$%
!H,'
H
%
"
'
")
('"*
'+
+ @" '3' 4:9 *' '+*"+
+
-
) ' 6 4:9 '
*
+!+
"#%9
"
,@)!M/65%
'+*
!'
" '
" 9 "##$%B
'+;94:9) @)
)
'+
'*
O
*
'
'8)
'
' '+" ''
/"'3'
,
!C>%
)
''8
!;)*'
=
'
H'
@;;-
O) +
% /" ' ') H
'''
*+
+
-
+ ' * ' ''+
g*
*
/
' B-9 !''+) % ''
+)!/8"##A%
A&
/ +
'+ +
+
;94:9 +
''
" +
!' 9'% )
' + !
''%H
1*)*'
9
())
'
' 69 ) * * ' )*
' S
('
( ;
'
'
'
1 .9+%%%
!24
@H
)
' +
' ' 6= ,/"
'
'
)
"
6=
'(
6=9
+
' ) H
) '
B> 3 ' +
6= ! " ##A% /65"'*
)BBB
B/65:!/65:)BBB%''
)6=!&.,.%
[email protected]"##%3')
+!"##&%"
!>'+ " ##&%" '(
6; , '''''
,
'
*L('
8
'!>"##&%
@" ' + '
) )* +
' '*
"
*'
'
''
' + '
" H
'
*
9*@
))
(
'/
")*
*
(
'
+!6B%"'
(!6BBBBB%!6BM%
61,
+
"'))
S
>9C"
)
+
+
)
6=O (e9-:*
9*@
A?
+
' *
*@ ' B +
( ' (' ' '
)
)
'
*
*@ B ] ) )
' +' ('
+
'!ML"##%
" ( * + "
:'+ ;[email protected]" )' 0$ AA 6="
''
*
9*@)
!j##%" !j####&% ) 9*@ )*
9*@3
''
' ') ) 6= <
'" *
9*@ ' ') '!d"##$%
"
)
'
'+'
+
)@
"'
'+
( '
O )
"'"
'
*'1"'
6=!'
%
)*
9*@)
- 3 * ;
+
" '+ 9*@ ' ' '
/
"
*
+
()'+,1
+)
*
(
)
' +
' +
!O06" O$6" O0$6% *' ' ' ' ' '
7)
'
"
)
''
6=
9'"
)
'
*
9*@
)
)*+
'(9
"
+)
*@ '3'" 8 " )* +* '+(
!/ /0%
*' 9*@ B '+ 9*@ *' *
7
* ' - ) 9*@ A$
'
B ' )
*
) ( ' " *
9*@ ) '
) ' !P
"
##$% - *
9*@ )* '
* * +) *
9*@ ) ')6=)'',
'
!W"##$%
"
)
''
9*@
'*'
+
' ! 4->?% ,
(
' BB , " * " ) '
') )
6= !T " #% ) *
9*@
'
+,)
6=/"+
M/65
'*
4:9M/65: ' ' !>'L " #% B
;99*@ + ' +
4:9M/65:
9*@M/65: +
, +
'
'* , +
3 4 9+ D &
9*@ '' ) '+*
!4:9" 4:9" [email protected]" M/65:" 9*@" ;C" ;:/ @9% B ' ( ) !'
" M/65% - ) ' '' ' *''+ )" )
'
"
' " ' ''+ 9*@ + , '
'
' ' @" ' )* ' ''+ '' ' , '
'* *@ B ' ' ' ; ' ' * -
'9*@*
*
'
"
A0
) !) ' * '' (% '
) !) ' * '3'% !;L '" ##% ''" )
''+ ) 6 , - '
(' '
'
'
''+-
'
*(
^:4
' (' ' + ' ; !C8 " AA$%" !=
) "
##0% '
'
3 '" '
'
'
)'*
'
" '+ + '
!
'"
"
'
q%
)
('''+
'
) '
- )
'
@"
'+'
6***6&***A
';9*@
'
'
'
''
'
)4:9
'*
'
' '+ ''+ +
- '
; 9*@ ) '
' ; 4:9 ';9*@4:9+'
'-
'
'
'
'''+
,
)+)+
)+
"
''
*'
( *
H
''+
" *
'
)" '
'" ' ' '
) ?
' ''+ ! 9*@ 4:9% '
(' (' '+* +) -
'
)+
'
'
' *
) + ' ''< '* ''+ @ ," )+ '' ' S '
)'
-" ' 8 ! '% '+
) ( (' - )
'
)
F (' [email protected];> != @( -( ;2
AA
,%
.
B4
"
!>E?
*2+"B
>(+% - +
) 9
>+,B *'''+3
''++/
-
)
" ;0 ;&" * ' 8(' ( (
!C'
) " ##% !
*% ' ; " * ' +
, 8('
+) @9('
) / -
) 8(' ( @9
( , * ' 3'
"P"
\
[email protected];> ' + ) '
' ' ) , '
"
''(';
*:
)
'
'
' !:
" ##0% " @9 (
+ (' +
, ''+" ('[email protected]/^! /'"##%
-
'"")
+)
'
'
' '''))
'
'
9*@9*@ )' + ' ,
'
'
4:94:9"
'
9*@4:9'+''
'
),
9*@9*@ - ' ' '
( [email protected] " % *=
;F
4:94:9r4:99*@r9*@9*@
- ' ' ; 9*@ ,
'
'4:9
)
'
'
' - 9*@ 3 * ''+/"
'
?(!6A"66&%
+
' - ' ' * '
6***6 " ) '3' -
+)
'
+
)
'
' ' ) 4:9 B )'' )
) ##
S ''+ 9*@ ' )
H, *3'' / +
' ''+ !9*=" -/;" M/65:""" >/:" B
\% '
) ; 9*@ '
6***6 / )" ) ) 9*@" 9*@"
' 9*@ ' '+
' - ) ) )
+ ) * S *@
@" [email protected];> 3 * '* ' '' +
)
-
''
"
([email protected];>'
;'9*@'*'
"
' ' - , ' ' +
'
5 4.9.+#.+9;.
@)
)'
+)
'
'*1,''
';*@"
H ' *' '
''
('
L*'''
4:9 9*@ ' '* " ))*W
+
!W"#%9
" ;99*@ )
'
'+
' , ''+ W ' '
''
+
, '3' F
'
4:99*@)
'
" '* 4:979*@ ' '
)
H!):%[email protected]"M/65:
% B )
, * @ '* '+ )
+ O '
' +
'@
+
'O0$6!*'4:9%
#
'
,'*
+
"",'
)
=
+
'
'@*'6='
+ != " ##A% "
'@ +
'
('
(;!-
"##?%)
'
@" +
'
'* '@
,'''
* '
;99*@ - 3 + *@ * ' ' 6= ('+!=
6" AAA% )* = '
+ '@ " +
'*
4:99*@ ;99*@ )
)
7 4.9.+ $# 9% +
'
)
' '
'+*'')
'),+
)
'
'
)* (* ' = )''" '*M/65M/65:N''
' " )
' ) *
9*@
)*+
6=
)* )
' ''+ D '+(
-*
'
)''
(
'(e
9-: ' >OM/- >/- -" *
9*@ )* ) S 9*@ 9
S 9*@ ' H + )
'
'H*
@
'
)*)*
/ +
) WL(6
8 )
L
L
2*@8
8+'
'
-
#
* ' ) *' )* ' +)
'+(
' '
+' )* '* *
) * '' ' ))'9
'
'';99*@H
S " +
* 9*@ M/65: !-
" ##A% " '? ! M/65% (
M/65:'9*@O'
' 9*@ 9*@ >OM/- M/65 +
:[email protected] 9*@ 9*@ '
9*@
'
'*)M/65: '
)!C"#%
5 , " )
)
) ' ;99*@ 9*@ 9*@ ''
M/65 '
9*@
9*@
'+;99*@"
[email protected];> '
9*@ 9*@ '
''+ @" ) + *@@
'
'*)M/65:'
)'
)
M/65
;99*@
9*@9*@ +
,
'
)
M/65: - '
* '
;99*@ +
(
M/65:
M/65
8 4.9.+$# 9
) ;99*@" H +
'
6= '" O$6 ' ) ;99*@ " , # $ "
"& _7L H
)
H
# H
-
#
)*
)*
)
)*+$
)*
*+ $
$
)*+$
9.+
','
(
)
+'
; 4:9 -
' , " )
'
)
)-
+,'
+
+
)
' +
( ;9
9*@ '' + +
" '
+).
S-'+
'
H @ " ' ' '
"H
*
) +
' +
' !O06% - *' ' + ' )
''
61
('42=
"=&0#%"
)
))
'
'
)))
,
')
'*'
:/-B ; !/ " ##A%" '
0# . '
''
)
' ' ' (!
#H
%'-
'
(',
''+"
+)
'
'
-''
9> ' ' S
@" '
;99*@ - ) '
) 3 '
'
' '' '* ' 5'" +
8 IJ ! S % '
# . )
'
'
1#H
'-'
;99*@ '+ !
* %
#
($#C
'
''+ , '
' +
'+
+
# " = '+ '
'
' + ' '' +
'
'
" 5:/;" [email protected];>" L" ''
" ( " '
)+-
+
+
'
'
'
+ ' ' ''+'')
-
'
'''7
'H'
)
'
) '+* 4:9 9*@
)*
)3
''''
+)
+
,
'+
'
'@'"
'++
3 + '3' + ( (
+
H
)4
)
)
'3 '
" +
' +
)+ )
' ) ( ''F '
''+
#&
##$%
#?
##$%
@'" " " W !##% >** L 2 ''+
W
=
$%%"0AsA#$
@82" >" KLL" " B" @" ('" C" L" T" " C" [email protected]" T"
5H2" @" 8
" C" 6
'" T" !##% 9
(
+( B
L(
'
@
2
44
&"?$s$
@"C"='"C"5"@"=L"W-"6"-"="9-" "=K"
WL" :=" W'" - !##% B''
' /65:)BBB '( (
' )
W 4
/*
4
'$"$##s$#$
@'
" @" @" " =" M" -" T4" ;
" B" " 4 !##?% (
(
;
!;-:%''+(
+'(
)
))
=
'=
(@%('$"0$As000
@L
" @" >'" W9" ) (" C" 4" M" L" W" =
" [email protected]"
:HL" C:" " " >
''" -" 9d" @K" !##% '
@
+'
4
$)"&0As&A0
@
" [email protected]" K" 9" (" W" T" W" " K-" 2L" " " C" =
2'"
CC" /
" W" '" K" !##$% 7+
(
'*
)
'
M/65+/=W#'"A#sA
@" W" 5L" " P" @" 5L" !##% -8
'7
* M/65 +) 8
2+
+
4
':$*"&&s$#
@'" 4" " -" C2
" T" T
'" ;" C2+" " >
" @" 5L" T"
@'
" " 6
'" T" BL" " !##&% 9
(
+( :
L -:9)(
2
-=
#*"AA$sAA0
@L" B;" =" @; !AA0% ( ''+ =
'=
(@%&#)"s0
@L" :" K" [email protected] !##% ''
+
F
2'4:)
)$"#s$
@" " =+" " 588" 9" " 9" @" 9" ) " WK" -
'
"
9" ;'
" !##% 5
'
+( )W=
-'#(+"##As##
@" "-
"9"588"9"6
"65"=+""6
" "-
'
"9"
;'
"!##%9*=
'
&@/=:*"
$#s$
=+" ;" C(" " >" ;" " " '" 4" C
" /" (" "
5L" C" ;LL" C" 5H" !##$% 4
'
' 2 )+()
+
6(
%,*"$#s$
=" ;" K" WC" 9" :" B" " W(" 6 !##A% @
'
@
'
+
'
#+"&$s&&#
=""M"-"C" ;"("4"
'""9"@K"="5"=
8"W"
;
'" 4 !##% '
@) 2 ?& +
''
+('
W4
W 4
#%"s
#$
=" " " 4" (
" " 9" " " " :
" 6" @" " ="
5" ;
'" 4 !##% @9 L )
'
@
-4
#*"$s$
=" @" -" >W" T
" @" 9" W" ;)" !##% (
' *
+ +( '
'(-%%$"0&sAA
=L" @" 9
" WT" '+" " =L" 5/" P
"-" :
" " M"
M" " @" 5
" " =L" " !##A% t*
'u '
'>'$,"?$s$
=" B" >" @" =" " " > !##% v/'
( +
'w
4
*'"s#
="B"6+"@"@
'"@"="/"+("9">"@";
";"C
"6"
" W9" M" @" !#% ) '
( -4 '
5F '6
:(
#####$4
%$"$#s$0
=" 6"=(("-" 2
"[email protected]"C("-!##%4
)
2
'(''=
'W&#("As#
='>
"C"@
"@/":"/"="9!#%4
'
M/65: L :+ ) +( ( =
%%+" 0?s
0?
=H" " " C" " C" " " @'
" [email protected]" " 6" =H" C
!##?% = ) 2 '
( )
'
''
-
&*"0$s00#
="W"9""-+L"T" "C">+L"4" '""C(8)";"d"
"6f" " "B"!##%-
'
'
(
2 565: @!00% - : '#" 0#s0$
=
" " K" e" " :/" >
" T" " e" >H'" @=" 2" K" ="
":"W4!##?%6
''
'
+()
[email protected]'
4&&&"$&?s$?#
='" -B" K+" :@ !A00% )
+(
'
/=W("#s#&
='"-B">"-"K+":@!A0?%)
+(
'
''+
'
0&-&*"?As?&$
=" " :" M" " >" 5=" " >" " 9" "
="5"5++
""-'
"-"-""!##$%5+'
+LF
'
(
#"###W4
+&"0AsAA
="=!##0%@(')2
''+-
- '*"#0s#A
=L" 9" K+" W" TL
" :" 8
8
)" ;" '" W C" " -6"
/" [email protected]" M" @ !##&% 4
) 2 '
'+(-:)'"&$s?&
=)" @W" '
" @" " W" :
" @" *
" @ !##% '8
4 ''+ ' +
t
'
2u+(
'=
'(!
%&)"0s0#
#0
=
" @" " W" >" C" :
" 6" >" W" -)" " " 5 !##%
M/65: !C:75L% ' *
2 '
/ )
+4
''"#&sA
=
" :" :
" 5" K
" " P'(L" " :L" 5" -
)" " " @"
9(
2L" =" @'" :> !#% 4
M/65: 2
2
M/65M/65:4&+&"#s
=H" " 5L
)" " 9
H
)" !#% @ :/;
''+ ' '
+( ))
;^[email protected];('4
'',"s#
=
"@"5L
)""6"@"6
" "@""-'"6">+"9
!##% ;''+ +
/+= =
- %*"
?s$
=
"@"6"@"@8"-"-"/"6
" """@-
"
@" @" " -'" 6" >+" 9 !##&% B+
+( ''+ '
-
- '#"s
=" /" 6" @ !AAA% t
+u =
( ( ))
'4
4T4%"#0sA
=" 5" =
" W" 6" !##% B
) (
)
'+((
'
(W4
:'*"As&
='
" 9" =
" @ !#% *
+ 4
:) W
=4
+
4
9((%)"?s
=5
!#% /'
'
5A0#
#9M
="M"4'"W"
"9"5'"@"C
L">""W"K'
"
!#%@
'
;9
(%"?As?&0
=
" B" e" 5W" 6+" " -
" ;" -
" B:" " T !##$% ;
)
''
) )( +( >BM ) ) '
[email protected] /[email protected]' /*=
#%"As#
=
)"/M")"C "M
(L("9/"/'
(L"T ";L"/4" +
"@6"-"
MM" CL
)" 9" /'
)" :6" @)" @ !##0% '''+
'
2
/+='+(
)W=
-'#+$"?A&#s?A&?
=
)" /M" (8" " M
(L(" 9/" 6
L" M" /'
(L" T " " @@"
@'L
"/"/'
)":6"@)"@ !##0+% >
'
)(
'''+ '
(
L/@
W=
-'#+$"A0&sAA&
=
)" /M" (8" " M
(L(" 9/" )" C " ;L" /4" /'
(L" T "
" @@" /'
)" :6" @)" @ !##% ' /@
''+
'F>*L)('
(
L=
(W)+"
00s00A
=
8"/":
+;
"-" +
"6"-
"M"""6"=":
)
"9"5("
4" >
''" :" 8" > !#% B )
+
L' )
+(()
'''+
'@); %'"A#&s
A
#A
=
)"W":
"5""""""@"
*"9
!AA?%-
''
'
+
+
2
"(
(@9
4
AA
&%("s0
=
'"=W"C
2"KW""M;!A0A% ('''+(
''+(
W=
-'#'&"#s#$
=
" W" :'" >" K
" @ !##$% 6/5 [email protected] ' '6
-%#)"0?&s0$$
=
)L'" /" 6
" C" =(" 4" )
" @W" P
" T" =L" ;" =L" -6"
P
" B" C+" !##% /*
' )
8+6/*96/9&"?s$#
=
2" " =" @; !##?% -
'
(
+) ''+
'9
[email protected] O @%,$"0$0s00
=
2" /" /'" " =" @; !##% ( (
+)
''+
'
'8
=
'(!
%&%"&0?s&0??
=
2"WO!##&% )''+
+'4&$+"&0s&0A
=
'" >" " > !##% M 2 !M/65% +
( '
@9B @ 9
+
B''
%%#"&$s?
=
":"M'""C
L
"4"@2"K""6/""CW"-
"W!##$%
=
( '
' '
'
* +( '
*''4)
#"
=
2"-="5"""""W""^"K++"@"W"":"[email protected]"/"
[email protected] !##% 9*@ '
)
' )
-'+/%#+"#$s#0#
=
2""W
+";"/L
"="5"6";
""
"-"e":P"";"'""
>" - !##% @'" ( C &7&" '
'
'
@ 2
W4
W 4
#&"0AAsA##
=d''
" ;" :H" 56 !AA?% 7
*
''
+'(-4
+
'"&0s&A
-L
2L"5-"^"">"="-" T!##%B
2
))(
4
'6
'+&"0sA
-">":"::!AAA%-
8
F
9 A&77P '
2 (
' ' W4
W 4
%)"?&As?&$
-+" -" 9
" >" C
L" " >
" ;" 5" -" >'" =" " /T" 6+"
K" 5L" " @" " !##$% @ ) + '
' --%%"?As0
- 6
' @ : 42
L !##0% -
') ' 8
' +
' 2( 4 &**" #?s#?0
-
"T"W"K:"e"9":
"@"-
"T!AA$%9
2
F
8
) ' +( :[email protected] ) =
' =
(
:-
''#$*"AsA0
#
-
" [email protected]" )
)" :B" " K" =" W " " K5" T" > !##0%
-
'
( +
''+
=
'(!
%&("0?##s0?#?
-'" 9" W" :C !#% '' 4&($"A0s#$
-88"@"5"M"-""-'"@" 28"W":88
" ":
("-"
-"-"=
"@" "B"!##% '/9*)'
))''W-B)%#,"?0s?A0
-88"@"5"^"W
"B"-""@
"5"6"@" "
" M" @" 88
" " " /" !#% (' )( '
@+'
'
'
'
@
;
'+M=
$%"$s$A
-"M"-
"@" ""5) "-":
"6!###%@(
'
( ) L +2 '@ 2(*
4
#("$sA
-" M" 5L" W" :
" 6 !##% '
@ (
*
'+([email protected]
-4
#'"0As##
-
" @" 88" :" 488
" " " " 9
" @ !##A% ; *@
) ) 2 L= ' )) 2 ' '
' -
:')"0&sA
-+" " " " " @" " @B !##% '* F
)'
W- %#$"#As#
-++ 9
" B" -" @" 9L'" :W" )
" M" ;'
" "
;
'" 4" =" @" =
'" !##&% + -## '
'
( '' * - * =" )( B
B''
%("As$
-+
"4>"@'"@B">
":"9H":""[email protected]"W
"6/"/L
"=W
!##?%9;/4
'@
2
W- %%)"A&sA&$
-" @" 4('" @" 9
" W" 9" W" ;" = !###% 46
)
(
'+'
W4
W 4
#,"?#s?
-" @" ;
" KK" :L" :" ;" = !##% 9'(
(
'
4/W$&'"?&s$
-" T " ;
'
" /" " " W
" :" W" :C" " !###+%
+
) '
F ( 2 2 +
9
[email protected] O @)("?#0s?
-"9!##?%5
:
4:)
-=
("&s?
-)" " -
" " T
" T" 5L" " )" W" 6(" " " " =
" -"
W";">
"-/"!##$%6
'/79*+(
2*
+)
'4
*'"0#$s0
-'"=" " /"T'"C"6
)"/"C" -:!AA% +
+= ''+ ' ) '
+ 9
4 @ O @ )," $?s
$#
-">"-
"@">"P"6
'"- ";)"!AA$%4
"
)''+
'("(
'
'/
'BM+
'BBB4
%)"&$s&&A
-";K"-"5""@@"@
""9":;";LL
"/M"/+"
@":[email protected]'
)"-"L
)"/";
'L":"!##?% )
+'
+(()-%,"$0s$A&
-
"TB"L-
"W "@'"K=">("@""5"/"[email protected]"-(
"C"
:8" / !##0% 9* (
'
)( ('
(
'B''(#)"000s0A0
-
'" -" 6L
2L" >" " W" 6
" K5 !###% @' '
''+*4 =
("?s??
-8
" T" -" 4" 9" 5" 9" /B" +
" W !##$% ;''+
' - ) )
(
F )
) //
'8
)
)'
')(WM
+%"$s0
-'" M" 8" 9" ;+
" 4" :
)
)" B" :8 @+" @ !##$%
>/6/>66B'
'
2"'2"
'
(-=
-=%("?&s$
-
" :B" :
L'" " " " =L" W" >
" !##% @ '
(W4
'+*"?s$0
-
'+
=L'" " " P" :'" =" >" C" >+" >" C" :" 6
" O"
:
" " :" 5" " 4" !##0% -8
:/; ''+ ' '
?A 2 ) '( (
'/W/
/5/
%*+"0s0?
-
'":"W
":"=
":5"9""6"9"M=
";"9L""
5" ;" =" :" -
" WB" !AA0% @ *)
'
(
L
''
(+
)'
"M/ 9:
B''(+"$s0
-
" 4"C";" )L(""4'">">"TB"
">5!##%
'8
(
' +( ''+
'9
[email protected] O @)+"$As0
-
" K" W
" 9-" " =K" T" @W" 9" C !AA$% B'
)
( +) '(
'-()"0sA
-
" W" *" W" '
" ;" -
K" !##% M/65
;=
' #+"00sA
-" @:" /'" !##% '
" '
''+
- =
%$"s$
-('" 5" " !##% ;''+ ** )
) /+=
[email protected]&"AAs
'
" -" =)
" 5" M" 9" 5=
" - !###% v6
'F K> @>
[email protected]
#,"s0
2
" W9" K" W " /'" !##% )
''+W
=
$%'"$AAs0#&
2
" W9" (L" :@" +" -" /'" !##% *
( '
''+ W =
$$%"
&&s?
("M"(":"L"C":'"4!##%B
(
)
2
75C)
))
(
L
W=
-'#('"$?0?s$?A
"6"K
" :";"/"6)
""6("-")"@/"=""
M
"9"5L""=
)"W"!#% +(
(;
'+(
'
*4*,%"&s&?
2" B-" L8" C: !##$% ;''+ ' ( '( 2 ( ( '
( ( 9
[email protected] O @%,&"#$0s#$0$
"C""6"H'"">"B"" "MM8"9W"=H" C"
=H" !##% ;'
) 965= '
'(' ' (
'
24:9
-)"#A
">"K"^":
"""4" "9"4("@"6"@!###%/*
'
(
'BW-WB-++"&0s&A
" " ='>
" C !##% ;''+ '' '
')M/65:'[email protected] /[email protected]' /*=
#&"
s0
" @C" C
+" 5W" +
)L(" " >++" /" 5'" C6 !##% * '
+( 6***6' ''+ ** ' W =
$&%"AAsAA0
(" @" K" [email protected] !AA0% +' '* ' +
2 '
2 ') =
( W (*" ?&s?#
" 9" " " T
" 6 !#% ;''+ +
'8
'
9'
()"&?As&$
+("WK":
+" W"=
("=">"/ !AA%
8
' ''
( ) ( ''+ (
)(WM
''"$0s$&?
/+"@P"5'"C6!##$%'8
(
''+
''W
=
$''"&$s&
/""C
" -" 8"9!AA%'
)'
''+(
+(('(
'+ #*&"$As0
/'"@"T""
(
""
+"5"9""="-!##&%M
)
'F
'
+)
2
LBW)=
&)"
&As?$
/"/@";"9"=
"W" 28">" ""5
":"("W"
@+L" " 62(" " (" " !##A% 42 )
'
F):/-B ;!)
%/W-*/AA#&*"0s$
/ >" " =
" =" 9
" 5" :
" @" -
" -" B+" @" " T" L"
C" ;
'" W" /'" @" !##% @ 2 ) '' +
'
)8
F+)
''(=W4
%$$"A$sA0
/9" " 9
)
" " W" @" " >" M" @" C
" 6" " W9"
+" " 8" M" " W5" !##% B )
(''
6
"54
'
(#$"#s$
/'"!##&%'+'
'
4&$+"&$0s&0#
/'" " -" T" -" -4" -" @:" *
" @" (" @" " @ "
"O"2"//":(L"TC"!##%'+
F+(
2
'
5/= ***"s&
/8"/"5""=+"/!##A%>
2''+
+((
(
''+4&*)"$s$0
/" -" -('" 5" " !##A% ;2
6***6L '
'
'/+=''+
'W
=
$+)"#s?
/)" B" T'H" " =
" 6" 9(" -" L" -" P(" B-" 5L" 9
!#% 4
#- (
(
2
'
'
-=
$%"$s0&
5+""W
"C")
>H"6"O""="!##%9
'''+
'9
'%,"sA
5L""9""@+'""9("C">
+":">
8"9">
'""
@H" !##% ) ) 2 '
+
'-)&"&0s?
5L" W" W" 5" =" @" 5
" :" 42+" >" P
" >" >
(
=" -" =
8
" "
:
" 6" 6'" " !##&% )( '
= ''4
&+"?s$&
5"@" 28"e")
"C"4
'
"/""":+"-!#%;
(
' ' + " + '
))-'+/%$+"0&sA
5"@"M"W"9"@"""5""9
"WK":+"-!#%
4:9 '
( ' '
=
%#%"&s?
5)"="@'"@"=
"9"=
"W"+
"9"5
"9"
"">"W9"
4" 6" )" 9" !##?% 4
2 M/65: M/65: '
'
))'
=
%,+"s&#
58" /" x8 )
" " =" " K
'" 9" >L" !##%
;''+
' ' [email protected]:/' ''+ W - %#$"
$s0#
5" " C
" @" C
+(" >" :" [email protected] !AA$% L '
+ '+ 2 ' + + + 4
%)"&As&&
5" 4" >8" KW !A0A% 9( ) +
2
)
=
'=
(:-
''%'%"0&s
0&0
5" -" /" -" " !##A% ; ''+ ' '
(
L
#"&?
5'" W" "W"=;"4!##%@)'
)
2
''+
'
+=9
[email protected] O @))"&A$s&A#
5
L'" W !A$% ;'
F '
4 / W #+*" 0s
0?
5" 9" 88
" " '" ;" -'" 9 !##A% :
+(
*('+
')-%'"?$s$A
5'-
L" " /2" @9=" *
" @" T" C/" /(" " /'" " '
" !##&% (
'
''+
)
2
+
W
=
$&*"A#$sA
5" 6" 6" C-" M
" @ !###% ; 2 )
2
W=
-'#(*"??A#s??A&
5H
" T" K" C !AAA% @L ' (
+( )
2
'W=
-'#(&"?As?&
5H">"P"=" "C";L"W" LL"!##%/*
"
'
@ ':[email protected] + ' + ( =:)%&"s
5L'""6
";"C'+"@"B8'"T"@"W"T"-"=L"6">"9"
W" :C !##% 9
' * ( )
2
)'+(9
[email protected] O @)+"?#s?#A
5L'"T"L""C
L">">'""T
"T""5"6
'"5"4"
C"4L2" B"O'"@!#% '/9*)( '
('W-B)%#%"A$sA0&
6+
)L"94" '":@";";"K" :">""6":!#%
'
* 2 ' + '
6 &+)"
?s?A
6" "-)"-M!##?%'8
'
'F
'
/
='#,"$s$?
6"M"5L"-!AAA% '
BBB
(
-4
%&"#s?
6
" " =+" :" 6'" P" " >e" ;L'" " L" " C+" !###% B
+ + )
2
FB))
*
'
)(9
[email protected] O @
)("&$s&$0
6" /" =L" W-" " W" C+" WB" ='" C" =
" W" 9+" W"
WL":="L" :"
":5"!##&%9BB
'
'!--B$$A%
+
''
'F4
--;'6
(W-
[email protected]' -
#$"&As&#
6
" T" " " -" K" '
" !###% (" ( (
' '
+9P
"+'
W-9(
%+&"$s$A
6" @" @8" -" -" /" +" ;" @" " -'" 6" >+" 9 !AAA%
+
''+ ' 2 (
@ +
[email protected] /[email protected]' /*=
%$"$s&$
6)" W" 6L" W !##?% M/65 '+( +( '
+
(
M/4-=
+"s
&
6+"" "4" "T!##%;2
'
2''+
'"
'
'8
'8
W=
-'#()"$$s0
6+"" e" 5W" =
" B" -
" B:" " T !##&% ' ;-:''+
'+;)
)
))
[email protected] /=W
[email protected]' /*=
%)"A#sA
6" >" :+" -" @+'
" @" 5H2" >" '" " =
8" - !##%
4
)
)
('
)([email protected]'@
@#$%"&#s&#A
68" " " T" '+" " 5
" W" =
" M" W)" " @" =" )
/" 9" >)L" 4" 9" -" !##?% 4
)
) ' ;
('
)((WM
+,"?0s?0&
6" :W" O" /:" 6" C" )
" M" 6(" " C
L" @
!AA0%4
'
BMF
+
(4
#%"#$As#A
6
" :W" @
+
'" -" -yM" " C" W" M" @9" 9" :" @'"
5-"@"K!##&% +
)
2
'''
-'=
%#"#$&s#0
6
" "-
" "-
"9"@" "6
"6"=+"";'
""
-
'
" 9 !##% ; '
)) 2 +( 2
4-=
&"$#s$
6"@"""/"[email protected]!##%9*'
))
')-("#$s?
68"W"="9-">
"W/""5'"@>"-
"W6"ML"[email protected]"
" -" W !AA% B ( ( 2 ' 4
( &%" $s$
6L"T"9
''"6W!##0%4
'
2
+")
'"
'
(;)(WL
=
+&"#s
#
68'9
L"P"-
";">8
"T"4"6!###%4
)
2
!M/65%
'M/65&M/65?&v
wW
=
-'#(*"0##s0#&
6
("WB"":
""
8"T "C
)("BM"T">!#%B
;
L
''+
'+
'8
9
("00$&
6n"69"d"6"@":"C
"W"/L"@>!###%;
;
''
[email protected]'
;'L6;("
###s##
6
'8" -" =9" =" 6" 5" " =" '" 9" L(" ;" M
" "
)" " -" - !##&% /*
'
@ F
L)
')
)(
[email protected]'@
@#$&"As#
6
'"-"C
L"@"
"T"9d"@":"W!AAA%O4
'
'
7-
-)("&&s&&
6
'" T" 4L'" 5" '" 9" '" !AA&% -
2
' +( O4-4 $('"&#As
&
?
6
28" " @+'" [email protected]" " W !A0A% B
8
)
'
+(()
9
4
@ O @+'"$s$&
6+" =" " @9" " -" 8" > !A0?% B
+2 8''+9
[email protected] O @+$"?&0s??
6L
2L">""W"6
"K5!##%9
)
'
''+9
[email protected] O @)+"00#s00&
6(L"=">"-/"K
" 9!##A%
+
)
+(
BB++->@9 W;
'+>'
W;>("As?
6" -" '+" =W" KL" 6=" 9'" =" (" W" :
+'" W " 6(" "
C
L"@!##%-8
+
'
@)
2
?&W=
-'#(("0#?As0#$?
6"-":
8"/:":'"M" ";"58"=":"W"C
L"@"
6(" !##% 4
)( '
M/65 ))
')-*"&s&$
6"-"T
"T")"W":'"M""5""W">
"-/"W";"
C
L" @" 6(" !##&% '
/ * ) (
$,("?&s?0
6"@"4
"@"6""@""M'+"" "6"=
"5
!##A% )
' ) '+(
'
*
[email protected] /=W#$"?0s$0
6
"K" ""W)"[email protected]!##% ;
''+'
'
'
'
'W=
-'#(+"0&s00
6
" K" " " 58
" " K" >" W)" [email protected] !##&% -
L 6 F ''+ '
' ' )
9
[email protected] O @%,#"$A&s$&##
6
" K" O8" /" CL
)" " +" W-" " " 58
" " W)" [email protected] !##0%
'
'
'(
*
)/=W
#("As#
>"@!AA0%:
6;9(
L
#()"&#As&
>'L"9""W":'":"K"e"=L
)"W"""
("9"=L"W"
W" 5" K" L" W" !#% @
M/65M/65:4
'
''L)+('
2W/*#,)"&#$s&#
>" " 5
L'" W !AA?% 9 ' '' 2'
-+'"&s?
>" " K+" :@ !#% >'L F * - %&&"
??s?$
>" /" K8" :/" T
" -W" L" :" '(" /" " @ !##%
/*
(" )) " ' '
@'W 9
#+"$s&?
>"K">8""@+" "@"-" L'"-"C" "@+"W" 2";"
L" " K
" @" !#% 4
( -i5
*i
(;''
'
'
2W/*#,)"##s#?
$
>"/"P8"!#%'
'
)8
@'
W9
%+%"?s
>" "K">@!AA%@+
'
2
!965%
*''+)
6
25
- 28
)"&As?0
>(" " 4L'" ;" ;" " C
'" ;" C'
" @" ;L(" >
!#%
+('
@4&+*"?As$
>" P" ;)" !AA$% 4
*
'
'
BBB-),"$As$&
>" >" T" ;" ;'" W:" P" ^ !##A% -( * @
)
+
'
) 9
[email protected] O @%,'"&?#s&?&
>'" W" :(" @W !##0% '' :
6;9F 2 '))
4:)
-=
)"?A#s$#
>" /" Bz" C" /
" @ !#% @ ''+ W
9
':%,"s
>" /" " @-" 6
" ;" >'
" 5" ;+
" 4" K" " C
" W"
>" [email protected]" " K" " " !##&% 6; + '
'
8
'
+
'4/W$*#"AA$s##
>'+" @=" >L(" :" L" " T" " K+" W" 6+" " 2(" :" @" C !##&% 9
' 2 /65:)BBB +
' '
' - - : W @' @
- : %%" ?s
??
>
":"O2"94!A$&%;'
'
''+
+
+(
'
(4#*("0s
>h8" :" -+
" @" 5*" -" :+" -" -
" W>" -
" W5"
/L
" =W" 9)" W6" @2" K !#% :
+
'
'
)
+W4
W 4
$%"?$s?0$
>8
"="9("-"=
"6">8
L"="P("B-!#%M/65+
4:9 M/65 '
'
" '* '
+24:9M/65:")[email protected];(#$
(
=
- ##"
$??s$$?
>8
"T"C'"-"C"4":":"4"6!##%*
))%,)"&sA
>8
" T" 6':))" 4" 4" 6 !##&% )
'L +
+
+
) '
) ( 9+ @'
@
@#$#"#$s#&&
>
"/" 2
"=!##$% +(
2
)
)
;
'+>'
)("&&s?
>
'" " 9
" W" -(" =W !##?% ;'
'(
+'
O "A0&AAA4
+"$s$
0
>
"/C"-
"=9">
";":
("C/"P'''"@6"W" "C
"6"
;" W9T !#% 9* ) ' '
''
WB''
='A&#%+'"&?#s&?
>
" W" 6" 4K" +'" 6" T
" 6" >L'(" " 92
" ;
!AA?% =
/9>'( 4L ''+
4$+$"$s$&
>
'" B:" P(" B- !##0% M 2 *
) C: (' 2
+
+
2
- #,"&?As&$A
>
')" C" -
" W" :
(" -" >fL)" :" :'" 4" '
" ;" -
K" " K" !##% ; + + (
$& )
2
!M/65%
M/65'
W
=
-'#()"?$s$&
>
";"-"T"K"TT"T"@"-
"T-"-"T-"K">"T" -"9" >" "WT"!##$%;
'
(
--:[email protected]'@
-:%$"$&As$?0
>
L"[email protected]"5"4"K"W"-"6""=""K!AA%;)
2
'(F
'
8
)
:[email protected]
/
='*"0#?s0
>" >"T"4K"K">"-"K5">"-"K
";T"W"T;">
";"
-" T !##0% 6" ) " ) M/65: '
'
)
#("$?s$&
>"="6
"9"=W
"B"B'"T"W8(L"W"=
""LL";">
";"
4L2" :" -" T !##$% 4
'
' ' )(
>657 5
2(
#'"&&$$s&&0?
>">"
";5"6
'"- !##%9*='*
+('
(+)::
@4
$#"As&
>">T"-"TT"
"K-";"TK"T"->W">" ">"9
>!#% ^
(' /@7*'(''+
'
'
29
("0?$
>" W" -" " P" WW" >" ^T !#% -( ' \
6
+4 =
#,"As
&
>+" " C'" :" " !AAA% ''+ '
')
/W- %%##$"&s
>2" WT" " WT" 9L" >" C'" C " C'" CC" :(" >W" " WC" >" =6"
C'"WK""="!##?%@
9^[email protected]
('
'2)+L
+
' ( '
C
B W /+
:-
/5
4
5
O @%("&As?#
>(":!##%BF+
"
'-%%,"?$s?0$
B+"@""T"9
"6"=
"-">
^"C"CH""
L"C" "
" H" W" @" @" !##&% ;2
( '
' 2 '@4
*+"0s0$
B
:
;(
(6
;A#"-
"6"=L("=" 2"/"
WL" :" " =" ='" " =L" W" 5L" C" '" " !##?%
A
9BBB
'
(
(
'2
(
'*
'FB
:
;(
(6
;A#W
-
[email protected]' -
#&"$#$s$
BL2" T" C
" >" 4" !##?% ' 6;9 : )
) )()
'
'
4
&,,"0s
B
" 4" K" -" /n'" O" -
K" !AA0% B
)
2 (
(
+ > '
'
W=
-'#($"#s0
B2'
";"T
"""/" "W";
'"W">
)"C!##&% (
8
565: ''+ 'F '
=
'=
(@%''+"#s$
W":C";
'
"/""6"
"W " "@6"=
";;!##$%
@
+'
4:)4
+"?#s?
W" =W-" :
+
" :@" 98=x" 5" =" ->" " CW" +
" -" W
"/T!##% +
'
*4&'("0s
W"=W-"L";"K"[email protected]"-"P" +
"-" W
"/T!#%
4
L '
* ( '* 4 =
%)"AsAA
W)"@"@
"-C"W">">8
"="686"@"K"4"/"C"@":"
(" :" -'" -" !##% ' '
+
)
2
@!M/[email protected]%
W-'*$"&s?
W)
" " /" " 6
+L" " '" !AAA% >*L (
''+ F ( ''+ * =
( W ((" ?#As
?0
WL":="=">"='"CM"6"-"@":"2""5(">"9" "
5" "=
2"9"!##?%@!QA%!#Q#%'
'+
A + 2 ' - : ''"
A0&sA0?
W" >" =8" @" >8
L" =" W)" @" n" " L" " @" :" -" "
;L""/
""!##?%-8
+(
!49%
!/60$% ) '
) 2 *
0 49
+
49C:W=
-'#+%"As&#
W
L
)"M"9H
"C"C"@"-
)"""B"CLL"/" L""CLL"
4"@
"C!AA?%@
))
2
"M/65-"
5!M/65:%C:!M/65:%
(
L/=W%*"A#sA0
C" ;" T
" T" B8" T" 4H" @" /8" T" 4L'" C" 4
" !##$%
9* ( * L '
W - =
' %,%"
As$
C'
)" 6" O'" @" " !##% 9
+2 =
'
(
(:[email protected] ( +
' ) +( + 2
(+
('W
+
=
$"$s0
CH" C" W
L" /" =
:'
" -/" P" @W" C(" @" /L" ="
" 5-" " =" =" " CH" >" !#% ; 'L'('
'=
%%("A#sA$
#
Cff";">L'"[email protected]"CL
" "W""">"4"6";'
""
@
" C !##?% 5
M/65- M/65 2 [email protected] /[email protected]' /*=
#,"?s$
C2'">""^"6
"C")"@"WL
+
""-+ 8" " '8"
@" /
'" " ='>
" C" CH" " !##0% 4
M/65
)
[email protected]
8
=
%%#"?0s?A
C2L" ;" CL2" ;" =LL" T" " T" +
" " T" ;" 5H2" >
!AAA% @ ' '+(
) '
) -'+ / %#'"
0A&sA#
C" =" W
" : " '
" - !#% >B5V >B5VF + )( (
*
'
2
4:)-%#"As
C":":":P"
"^";++"@W">":K";
'"[email protected]!AAA%
M 2 C: (
L )( +(
(
2
)
(
W=
-'#(&"?&s??#
C/:4>@4" WK" @=4" :5 !AA% @ ' ' 9
(
-#&"$s$&
C" =" :+
28" 4" M)L(" @" C" " 4" 6 !#% 9*@
'
'
'
+( ' M/65 +565
=
%%+"0&sA?
C'" W" " KW" 6
" 4" T
" T" 6" - !#% '
/9*
M/65 )
' ) +L ''
6)#*"AAs
C'"W>">(";"-"@:"/'"!##A%
('
''+
'
'>BM=
'=
(@%(++"0#s0
C'" "W
";W"+"@"T"" '"WW"=
2"WO!##&%;''+
(8F(
''+
9
4 @ O @%,#"$0s0
CL2";" '
"@"C2L'"@"C
">"5H2">!AA&%)*
''+ " " ' ' ' )
('")
(''+)-'+/%#%"#As0
CL2" ;" '8" " +
" " >" ;" ;" " =LL" T" T" ;" 5H2">!AA$%4
'
BBB7''
)(
)
H
'4
%)"AA&s##&
CH" "C
L2"C"9H""@+"-"B+h{8"-5!##?% ''+ ' :/; )
+( /[email protected] '
#*"$#0?s$#A&
C
'" @" '" " @'" :>" 9d" @K !AA0% ; '
)
)( *
'
'8
W =
-' #($"
$?s$
C
"C"482";"5""@" "T''"/"W
"C";L";"
L"
:" T'" > !##A% [email protected];@? '
' 2 +(
'
*9
[email protected] O @%,'"AsA0
C
L"@";)"!#%''
2F
'-
>+9=
$
C
L" @" " W" 6
'" - !AA% ; '
'(
''+
2
'
-(*"0AsAA
C
L" @" )
" M" :
2" /6" ;" T;" 6" :W" 6(" !AA$%
4
'
BBB
-),"$&s$?
C
" @" 5" " C
+(" >" :" [email protected] !AA$% @ $# '
2
'
' ) '
'( ''+
4
%)"&s&$
C
"9":)"9W":H+("O"C
">6!##?%'
- F
'
'9
[email protected] O @
%,$"#&s#&A
C
8'":" " "@'" "'"!AA$%:
'(6;9
2
'
F +2 '*( +( ->" :" (
+(:
@(
-=
%("#s
C""K
L"C"=L":" '"-" ""=";"="K/"
" : !##?% -
)*
)) '(
L'L'#,"A&#sA&
C+8L(" C5" :" K" 68L" :" -
" W" C" :" K
2" " 4'" "
""C'd"O!##% '+(
''+
'
'
(
-=
-=%%"#s&
C'" ;" " M" -" e" -
" e" K" -" @" W" =dL" K !##0%
+
L '(
'
=W4
%$%"$As$&0
CL"9"O+"O"=
"9"=
L'"@"5+":" )
""K""
'8" C !##% B+
' 2 ))
+( ('
' 2 '
+
( ) 2 -:'%"??s??0
" --" /2" @9=" " !##&% 9
) +2
''+'
+
)
')/&
)
2
+
WM
()"AsAA
'" " >
" 5" W
" 6" >
" W !##% 9
(
(
M/65:
M/65)
-'
@9C70
#$"s&
'
" :/" '
" /W" -" W !##A% @
'
9*
'
')
'
)=
$$%"AAs#A
" @" P" ^" 5" @" P" P" :)
" 5" " C" 9" -"
P"W"K"T")"6"!#%;
(
'
'
M/[email protected]
)-#*"&?s?0
"/ "
""="="4+'"-"P
("-"=2"W")
"C"2"
C"
(""58>"K"!##%B(
'
'
4&,)"0?#sA
" " @L" B; !##A% B
'
(' ''+
9
9+9
%+"s&0
"">"W!AA0%B
''++(L
+
L
+
9
$%"&#s&A
H
" " -
" =" +L" >" ='+" -" :
" W" ='+" / !##%
/*
M/65" '
/@5" ''
49 49))+
"'
"W9
#,,"?s$
"@"="B"9" "M"@"5
"6"-
""":!###%
M/65 )*
( 8 '
)*
'
'BW-WB-+)"?$s$
" ;" C'" -" 6+" >" O'" ; !##A% ; BB++''+
'**''+/=W#+"
&s?
''
" @" 5" W" ;" >:" P" W" /'" !AA%
( '8
''+ =
'( !
%
$%"$As$&
" T" '
" " >H '":" MM" " 4
" @-" "
" >'" " )
" K !##$% -
' ('
( '
+( 4
7 '
@'
9
[email protected] O @%,&"&&&s&&&#
"K-"" " 2L" "-("T"9"e"-"T"/+
"-"T" W"
C
"@K"K"^"!##$%5
+
L+
'
'(+
(+(W
=
$''"0&s0A
":"4'">T!##A%
'+
''+/*-:$%*"0$s
0$0
2
" " '
" C !##% ''+
8 $#("?s&#
"6"T"^"P"P";"9"4">"@+L"B:"""B)""=L"C"
T"W !##?%@(
*
'
-i'
+
' - *" ?$
">"W
"P " '"@>:"5
"9W"-"^"6"C-">"^!##% +
'
*
)''(
' '[email protected]@A:
'*2
9*--%&#"$As$?
" " =fL" " 4
" =:" 6" " B'" C" 6
L" >" -
" M9
!##&% - /65: '
+ /65:)BBB )
(
(
'W
=6+$"A$sA?
" T" /'" " 6" !##% 6
' ( ''+ 'F+ )'
6
'=
$"##&
" W=" W(" " " " " [email protected] !##A% M/[email protected] '
)(')
)=
$$&"As
'
@F
" 4" L" >" K" " -)" KC" =" 9-" W
)" @" "
=K" C" 9 !##$% ; ##$ K> '
)
('@4
!=%%%&"A$s#A
)" [email protected]" >
" C" )" 4" )" W" " B" W
" /T" /
" :
!##% ; + '
) +( (
/@4 =
%,"0s00
"9"K)"M"K+"P!#%;*'*F('
W-=
%)'"A&s#?
/
)" @C" 9
" T" 6
" W5 !##A% +
' )
)
2
(--:[email protected]'
@
-:%*"&0As&AA
" =>" " ;@ !##?% B '
-
-=
%+"&$As&0?
"T":+"":"[email protected]!AA%-
F
+
(
2
-(*"$s$
(" W" 5" C" 5'" =" " @@" :
+
" @W !AA% >
'
)
2
+(
*)
)WM
'+"0sA
6+" 5" 9
" @ !##&% + M/65 ' M/65
F '
'
@' W 9(
> -
9(
#++">0&s0?#
6+" 5" 9
" @ !##?% ; + M/65 F-
'
9
-
'=
#"0#
C8" C:" 9" W>" /'" !AA$% @ ''+ * 'F
'
#('"s
" /" ;'
" " " 9" -'
" " 6
" " =
" " ;'" 5"
4" =6" ;
" " -
'
" 9 !AA?% @ '( ''+ 2
'
(
/;
(
2
9
[email protected] O @)$"?$s
?$0
" [email protected]" 9L
)" /" " W !#% - ' F '"
("(--#%"0sA?
""6
"M"M
"6"=
)"9"9
"6!AA%B
'[email protected]
)'+(
9
4
@ O @++"A?$sA$
""6
"M"M
"6"5
"6"@L
)""@
"C"M
"
" " CW" -
" WT" 9
" 6 !AA% ;2
) ':[email protected] " 2 !965%" + ' '
'
+"A&sA
"/@"="-"K"9T"
""
"C":
"@"C(""5"="
" :" " 4" !##?% L ' 8 '( ( +
' +( ( 2
'
(
+
'-:''"&#s&
" M" W
" -" :(+" >" ;L" 4" C'
" @" CL" >" ;
)""K"K"5":>!#% '
-6
9*
=+)
'
-4
&'"As
H">>"-" "4
" 9"4
": "KL"@"K"6":
"C/"
" 6" -
'
" @ !##?% @ ) '@ '
H('+()'
W4
W 4
#'"$#s$0
L";"
"="C";">'"O" L" "C+""/L
"O"
@
"C!AAA%+
)
2
=
(
'
W=
-'#(&"$s
'L":"6'"P"C"/"6"4"6"W"C+"!##%
4
+)
2
?&"
2
"
)++
'W=
-'#(("00s0&
"5"@"P">'"@6" ":">L
"[email protected]!##0%)(
'
&>;
/=:)"?s?A
" 4" =
" W " C" : !AA#% ;''+ '+(
;
'* #&)"$s$$
" 4" -
" " ;(
" W" 9
" W" >
" -" =" M !AA$% ;
''+'
;
;'
4$"0s00
" " T
" @" =" @" ;)" " :+" W !##% +( '
#)$"
0$s0$&
" C" 5('" ;" ;L" " 5H
L" " C'" >" BL" !##%
' ' *
2 '+(
:6 ( 6 -
)
-)"0s0A
'
" ;" =
'" " *" W" =" ;" '+" @" " 9" K" "
KL"-" e"W>"K"-" !##&%M/65
TA&
'
; @'
/=W#&"s&
L":" 4(=-)" C;" 9(" @" =" ;-" -
" @" C
L"
@ !#% ;''+ '
' '''4&(,"&As?
"@"6n8";"C
"!##$%>
(
2
')
-:'("##As#?
" -" ;'L" >" (82" T" @'
" " '" " " ; !#%
;''+ * ''+ + H*''+
'4
9
[email protected] O @%%,"??s?&
2" //" P
" " /'" !##?% (' * ''+-%#("$s&#
" >" ;" KC-" 5'" :/" W" CL(" K !##% /*
)
2
'4
$&&"
?&s?0
""
'L("/"@'"B" ":" L"/;!##$% '
[email protected]
L+2)
('4)
#"
0
L
)" " K
" @" >
8'd" >" =" =:" >
" / !AAA% M
2
*
'+(
/6:=
)$"0s0
" 9" (=
" -" -
" @ !#% 4
) F
*
p4:)-%%"00sA$
(L":@"C'" "-"@:"/'""=
2"WO"+"-!##%;
( 6^^^6 '
''+ ** '
+( ''
W=
-'#()"?&As?&A$
" W" =" =" C" -" ''
" @ !##% ; ''+
'
/+=
''+W=
-'#(("$#s$
(""-""K"@"K+"W"@">6"P""8"
-" =d" " :8" >W" " - !AAA% @ ) ) 2 &
+( )" M/65/" ' ) M/65: !C:%
+
M/65:!5%
(
L/=W%+"?s$
("[email protected]"
2" W"
"B:"98("[email protected]"W+"/K!AA&%5+
+
2
!565:% ''+ '
-
8
(
' 2 46%%"?s?
" >e" L" " 5" " @
" W" :" [email protected]" C+" !AAA%
4
' 7'
BBB +
'
(F '
)
2
?&W-=
%&'"s
" >e" L" " 5" " @
" W" :" [email protected]" C+" !AAA+%
4
' 7'
BBB +
'
(F '
)
2
?&W-=
%&'"s
" >e" " 9" " >" L" " C+" !###% 4
*
+(
'
'
'
[email protected] /= W 9+ 5 @' /*=
%&"&s&A
"M"=L
)"!##$% =
[email protected]/-
=
))"As#
" " >8" =" ;" " -
'
" @" +(" " :" :" ='" >" 4" 6 !AA0% 4
2 W =
-' #($"
$s$0
)" C " =
)" /M" 9
)
)" T/" =
)" M" -" MM" @)"
@ !##% ''+ ' ' /+= /+=
(
LW
=
&,,"s
"@"K"=-" "/6!AA?%+)+(
(
'
+
W4
+*"#As#A
" " 68" 4" C" [email protected]" " W/" L" -" K" " ;" " W" W9"
>" @W" K" " !#% 48 ''+
*' *
>BM+(''+
''''+W
M
+'"A#sA
6
"-">
'" "@
" "6" "9
(L("@@"K""P""
=dL" W" O" @ !#% >(
+ ' +( ' ) 2 !965:% \ ''+ ' W =
-'#+("?$0s?0?
L
('" T " 6+" >9" 5" 4" 6" -" @
" W !##&% 9
))M/65
'
)
'
)+L
)-'+/%$#"AsA&
d"K"6"[email protected]" 28"W"-("6"/
"B">8"O"=d"9"6"
;"=d"K"'" "!##$%@
*
'
@2
'BW-WB-%#%"s
4L'"5";L"";L";"C+":6" '" !AA0%4
*
'''
7BBB
2
4
#%"#As
##
48L" " " " >
" ^" ;L" ;" " ^" ;
" 6 !##% 8
+ =
%%'"#AAs#$
?
4" -" :
" " W
+" " :
" " C
" /" ;" @" +
" 6" 9
" 9"
>+"9"-'"6"!##%9+
''+
'
+
'
2))
#)"0sA
4
" C" 5" : !AA?% )
+
+ 2 +( '
*" ''+" L ' W =
-'#(%"&#As&#&$
4"6"C"">8
"T!##%;
4
4
2(
L
M/[email protected])/*=
*%*"0sA#
4"9"+"-!##%
'8
'(
+(''+*
'
=
'(!
%&)"?0A?s?A#
4'";"5L"T"C
"C"T'";""T"C'">"C+"C
!##%-:9
84'+'
(
*
24-=
*"0As0?
4
+" -" 8" B" " 6" 9" " >" @" -" 9 !AA0% @ 2
''+
:
'(":"
'
'+(
'
W-=
%&%"0$sA$
4
+2" "K+";"C"9"L">!##A%B>'
'
)
(
+
'--:[email protected]'@
-:%*"?##s?##$
4
";"T"4""/""T"4
""T'"4";
(
L";"O('"
"6
'"T"C'
"@"!##% +
'
*
4&'("s$
4
'"9!##%;+!W9'%-B)
/
###$"sA
-
" =9" ;" W9T !##0% ; )
) '
* ''('F9*@
B''
:&%"$s
"/C"C''"W"C'"9 "@+";!AA%^(
6-4
8"2
"
#*&"&As&
" W" C" 6" *
" @ !##% '8
+)
965+
''+ ' +( H*''+ =
'
=
(@%()+"?#&s?&
L" >" C"9 !##$% 62( '( ( +
'
@'W9
%(,"&s&
'"B"BL2"T"C
">"4"!##%; '
9*
=6;9)
:: $,*"0?s0?&
L"@";
'
L"T!#%@
'[email protected]*
(
4
*$)"0s&
L+
""C'";"5H"T"
8L" "4L"T"/
'
">" "T";
('"T"
L"T!#% '
@*'
8
) 2 ?&
'
( '
F '
( @ :' '$" ###s##A
" =" 9H
" C" C" @" )
/" 6" W
L
)" M" L" " " @"
9
" :5" @
" C" /L
" O !AA?% M 2 =" )
2
9
[email protected] O @)$"&$?s&0
$
" =" 9H
" C" )
/" 6" -
)" " @
" C" /L
" O !AA?+%
6
' 8
'
' ) 2 =
!M/65=%8
'W=
-'#(%"A#sA$
"@C"'+"@"C"W"-
K"!##?%M/65
)
4:)
-=
("&As$
">";
L";"4"">L">"@+"T";"@"CH'">"T'8L">"
O('" T" 4L'" !##% )*
!4:9% 2
'
'@:#&"&$s&&
" :" >
" @" CL" 4" " " " " C('" T" C
" B !##?%
/*
'
" ) 2 " ''
'
)
'F
) 2 '
)
'>'9
$("s&
L" PC" L'" [email protected]" '" @B !##$% M 2 '(
F)2=
-
$+"&0s?0
)
"-"-" "='"CW!##%
'8
"+
"
'
+((
@L'8
'
''+
'
(6
W=
-'#(+"A?AsA$$
9"e"-("T"K"T":
"4";
":C"9"5"="@";)""
C
" @K"K":W !##$%4
+ M/65 '
W=
-'#+#"#As#&?
9"e"-("T""K-" 2L" "L"W":
"4";
":C"C
2L"W"
T" 5"9
"6"!##$+%=
L
)2
M/65
+'
2--%%"&s?$
9L" @@" 5" 5" " K=" @'" @" 8" " :'" 4" =+" "
=" -" C+" " /" !##% 4
' F
*
"
"
@'W9
%'&"As&
9
"K"W
" "P"^""W->"(":W"@"9"L
"9"-"
>" "B"6"6"!##0%@
'(
'
+
'
'
' $#%"0#$s0
9"/=!##%/
F+
+(
4:)-%,"?&s0#
9
M" /" " " T
" T" W" ;" @+" !##A% ( ('
+( '9*
4&*)"0s0?
9
"@B"9"-" 2"5W"B"" '"5W"@)":"6
+""
M+" :" 4(" C4" TL
)L
" " !##% 4
' '--%+"??As?0
9" " ;+ " C" >
" " '
" !#% @ @'
@
+
-
);''+9
@)
9)6
25
\
:
B+
W=
-'#++"$$s$0?
9
"6"@
" "K'"@"
(
" ";))"M"
L"B"6"W"
"
C " '" @" " >" !#% - '
(
' '(
)
(' = W 4
%$&"
&?s?$
0
9L"@"'
8(L"@"'
L""L":"C
2"" +" "=""
6
" C !#% ; M/65 " " ' )
('
(L'BW-WB-%$$"0AsA?
9
L
2L" " C'" " 9" " 9" @K" +" -" =
2" WO !##$%
;''+
'
'(
8
''F
+'
'(
=
'(!
%&'"?s$
9
L"P"-
";"4"6!###%;M/65)F
"
"
' '>8#*"?sA
9
"W" /'"!AA#%'+
'8
F2
'
=
'(!
%#)"#s#$
9
""T
L
('"--"9'
"""="@H
""-
":"9"@"
" @ !##% M ( +
''+ W M
+&"
?$?#s?$?0
9
" =/" +" - !#% * +( ' ' ++(''[email protected]'
[email protected]'
*'"AsA?
9" -" >
" " " @@" O8" 4" C" " >" 4" '
" "
4" 6" @" >6 !##0% 4
M/65: '* 9P
+
'
W=
-'#+$"&#s&
98("[email protected]"98L"K"P""6
+""="K"='"W"-("W-">"
=" )
" :" 2" " !AA?% 5+
+ 2 '
= )
((
'46%$"AsA
9
2"=K">":"4
"K" "e"=L"W""W" ";"9
"
"9L"WC"L
L
"B"!##&%/*
4
"L
W"
'))
-:'*"&s?
9d"@K!##%;
7*
'*@)/*=
*%*"$s
0#
e"W>"-
K"!##%M/65)
L
L/*-:#'$"$s0
:"[email protected]!###% '
)+)+-
4
+
%,"00sA
:"=C"K":4"=" >"="!AAA%
'
'-
%%"?s?$
:"W"CH"6" '"B"P"T"6
"M"C'""5
"-" "C" +
"
" " 5" !##0% 9*@ " '[email protected]" '
'44
%%"#sA
:8"W"5""C
"@" :"[email protected]!AAA%@
')
'
+(*
'
'
W4
W 4
%)"$0$#s$00#
:" " L
" =" =" " @" " :
'
" M" @
" W-" L(" 4"
P" =" +8L" -" =" 5" !###% *
'
!-:97OB9% + ( + -4
%'"s$
:" " B+" @" (" 5" " " >
^" C" " WT !#%
9'(+'
$()"A0sAA?
A
:M""9":"=
"";
" "B)"6"-";""6"9"/@"
" 6" " " !##% ;'
)8
) +
' 'L4&'+"0s00
:" M" P
" " " >" *" @" " @" ;" =" =
" 5"
=" 5" @
" :" 5++
9(" 9" !#% 5 + '
+F &(
&$&?=9
P 28#%"?s?
:"K"5''"B!AA&%M
@:)-)=
%%"$sA
:88
" " :+
28" 4" :
" /" 8" " " 6" 4
'" W" 4" 6" ;'
" !#% 4
/65
-
:(#"&0#s&0
:
'" =" '(" @" '" " 9d" @K !###% 9*7
'*
'
+(*
'
@))$"A&s#
:
'" =" :'" =" C+" =" >
)" B" 9d" @K !###+% ; '
@
'(()(
'6;95/= &+'"?0s$
:
L" B" MH" C" :" W" " K9W !##A% 9* +
(
*
'
)'
'=--)"A$
:
" " =" @>" 9" /@" C+" !AAA% >' '
#")(6
'*("&As?#
:
" " 6
" " C+" !###% 6
' 8
'
F +
) +
'6
'(,"s
:
" " 4" -" 6
" " @" " -'" 6" >+" 9" =" !##0%;''+
'
+
=
-%)"??s?&
:
""C
"/" LL" "-'"6"@""="!##A%;'(
'
F
')
'
(-
- ''"?As???
:
(" :" " :" " !##% (
+) ''+ '
'8
)=
'(!
%&$"A?sA$#
:" K" =L" M" C'd" O" " !##% ; +2 '+ (
''+ ' ''+
8W=
-'#()"$s$A
:+" W" C'" W" 82" ;" P" " K" " " 5" '" @
!###%@M/65+
('
+
'
))+
)
4
4T4#"#?s
:dL" @/" " 6/" " 5" 5H2" >" " CW !##0% '
[email protected]
*
'
4)
$"
:" K9" /'" !###% ; 6***6 '
F '2
L ''+
**
W
=
#)'"AsAA
'" 96" +dL" !A$&% =
2 '
+
''+ 9
4
@ O @(#"s
(" @" C'" ->" L(" W9" -
" /" >" :" 6(" " C
L" @
!##&% '
'
( '
' W
4
W 4
#*"?s?#
#
L
" T" C'" @ !AA% -
''8 ' ''+ '
)')+(
')'
(W-=
%#*"&s
?
" 4" 6+" " " T !##% ; '
!e** % ) ''+ ' '8
))
=
'(!
%&$"#As
8-+(
" " " 4" 8
" WW" " K" -(
28" /" =+" ;W"
9(
2L(" =" 8" @:" -" 6" -
-
" - !##% 6 )( +
[email protected]'
(@'W9
%'$"&#&s&?
)" BM" =LL" !AA% ; ''+ ' (
';-=
&"AsA$
"""T"9" "B+"@""W"("5"/>" "=
"="
L"C">
^"C"!##A%B
(
'
'
+
'L
'W-
[email protected]' -
#("&#s
&
""@"C6":
2"5"(""=8"@6!##0%4
*
( ; 2 B''(#+"#s
" " ;L" " " C" >" ;" 5H2" > !AA&% *
2
" *" ^
( *
+ W
4
W 4
%*"AsA&&
2
" @" ;L" ;" T'" " +(" !AA$% ; ( ?A
(
L !M/65:% 'H
+ 9-''
=
'=
(:-
''#$+"0$sA
" !AA% - @ 4 T @ '$$"#&s
" " /'" !##% [email protected]/^" '' ''++
''+W=
-'#(+"#&s
""/'"!##%
2
'+
'''+*
W
=
$&$"$AAs0#
""/'"!##+%B)
)'
''+
'
+(7+W=
-'#()"A0#sA0?
" 45 !##&% ; $& ' )
' 9
4
+
(("#s
8"6/!##%;
+
''+
=
'=
(@
%*'*"#0s$
28"e""->"M"W":+"-!##A%4
2(
2
9
[email protected] %,'"
??s??A
(" "5
":"5+""=("=";(
" """ ":"
""
T" K" " : !#% ;
+
' 'L ' ) )
''( +
' W 4
W 4
$#" A&#s
A?#
">:"=
L" "C
"4"@2" "8+"W"MH"@"5"@":+"
-" =L" " >
28" @ !#% ; (
' ' )5/= "@"6""/'"!###% (
'
''+F6***6'
(
2++
+
W
=
#)'"AsA?
"@"O+*="B"/'"!##%;->(
+
F ' +( ( ''+ * 9
4
@ O @)+"A#&?sA#?
"@"/"/"6
"K5!##%5
''+
F
"6***6L
'
- =
%&"?&s$A
"6"M'+""P)" "
"6"=L"-"-)"5"P''
""
9'
" " ;'
" " " " !##% - '
)
'
+(+
4&#&"AsA$
" W" C
)(" BM" " ;" '
" C=" " -4" )
)" :B"
=" 9-" 6" 5" =" W " 6
" K5 !#% -
'
\
''[email protected]'-' %$$"$0s0
" " =+" C:" 6" -K !##% B
+2 /+= /+=
''+
'+(''+5/= *%)"#s#$
8"9"@("/!A0%=(
'
(
(
@4
[email protected] &%'"&0s?&
8" 9" " " C
" / !A0#% '
+( ''+
((
(4#+*"&#s&
"C"-
2"-K!##%6'
(
'
(-
>+9=
#"##0
)" @" P)" B" 5'" 6" " :" >" P" =
" B" '" /" =8" @
!AAA% '
'
W4
'($"A?sA$
>" 4" C" " 9" -" C
" W" @" >" 4" 6 !##$%
4
M/65'
+(M/65:
[email protected] /=W#%"A&sA?
>" 4" C" " 9" -" C
" W" @" >" 4" 6 !##$+%
4
M/65'
+(M/65:
[email protected] /[email protected]' /*=
#%"A&sA?
"T"" ""^"W
+"W"-""4"T"W"e"K";"T"K!#%@
' ) + - ) ( >
=' *'" &#$s
&&
" W" 4
" 6 !A$% ; '
'
''+ %(*"$#s$
" C"-L"B">";"L"9=!##%-')
('
'
#$"$?$s$$
" C" >2L" -" -L" B" " [email protected]" =(" W" >" ;" >L'" :"
-'
" " L" 9= !##+% B
' + '
4&$#"A?s#
L" ;" 4" : !##% 42 '
' )
' ;
4
#&"#$s
'">"6"/"=""-
":"-*"4" 8"@"M(":"
)("
" 9" T6" -
" @ !##?% + ' [email protected] )( *
W;%&"?As$#?
'" W " WL" := !###% 6 'F "
"
'
5
=
WM+*"s
'" "=
'"=W!AA&%'
**
''++(
4:9
[email protected] O @)#"00sA
'" " '" - " =
'" =W !AA?% (
+
)
)+'''+
7+=
4
=
$"&s&0
'" " "" L" "6
+L""P
*""@'
" !##% ''+'
(
@''++(=
'(!
%
&,"?&&s?&&0
" " =" @" CLL" 4" :8 @'
)" -" :'" " K" /-"
@
L" :" >" T" " W" C'
" K" !#% ; 2
7
2(+
2
'
+
'-%*#"#?&s#$?
" T" '
" ;" 5'
)L" " " " " 5" " >" 9
" "
T"">
'":"C" " !#%;
+
'
)
9
[email protected] O @%,+"$s0#
L" " ;L'" " " >e" 4" 6" C+" !AA0% 4
*+(
'
'
)
2
-)#"$&s$&
L" "
">e"4
'"";L'" "C+"!##%M/65?&'
'
'* M/65: M/65?&
+W-=
'+*"&$s?0
'
" =" " -" -" KW" @+8" " =(
" !#% 4
)(*'
''
'(9
[email protected] O
@%,+"##s#&
L(" 4" -
" 5" =" =" >(
" C" e *" 5" =
6
" /"
-
" @" P" =" ;
'" W !##% '
+( '
W 4
W 4
##" &AAs
?##
" 9K !##% @ )2 ( '' +
';
-:;#"#&s#
L" @" )"C"-" -"M"@"
'";"4"/":
" " '
"
:W"
8":"C";"!AAA%=
(
)
2
)
) ( 2 ) '
' W =
-' #(&"
$s?
8"@"M(":""@"
)(""=
""-""9"6T
!##?% @
'
) + ) 2
+
()"$#s0
" W" =H" " *" 4C" -" :" =H" C !##%
4
(*'(
)'
'
' +F + 'L +
BW-WB-%,%"#As
)" ;W" @L" B; !###% '
'* ' ) ''+
'p9
$)"$s#
)" " -" " 5L" @" K'
" " C
" B" " 6 !##% 9* =
'
'F * = '
WB)'
%$,"??s?&
'" " @L" @ !##% B *
M/65
!5;" C:"
4:9% '+
2 '
'
) " )
("''
'@
'"A&s#
":"
"K9")="W"K""5"=";
"W="="
C" =" @@" " -" =
" O" !##&% :
( ' H)'
8
'
+
'4/W$*#"A0$sAA?
'
"T";""T";"@L"T"4
H(
"T";''L"4!##%6
'
+()
))-'+/
%#+"s#
H
" / " L8" C: !##A% + '8
=4B9
''+
'=
'(!
%&+"&#?s&#
" /" 9
|" W" =" " @" " ;
+'" 6" L
):
" ; !##0%
4
"
)(=
%%%"
#?s#&
" 5" B
" C" O'" " '8" " L2" T" +
" " " ;" ;+
" "
;L'" " T" ;" !##&% 9* ' *
) ) +
''+'
(
)+W4
W 4
#*" ?0s?$
"@"P"^"
2":"C
"T9"C
''"= "
"94!##0%
'
= "&(
*()' + '
'
/
='##"$#s0
28" W" C" :" '" !##% 9*=7:
6/5' :
@
)
)
)
(
L/+= W-=
%'*"0?As00#
28" W" K
8" ;" '" !##0% /+= ' ( )*=W=
-'#+$"0AsA#
2":"K"=!##A%@)
)
'-
:%,&"&$?s&00
(" [email protected]" >" /" n+" K" P
" -" >
" " 4)" [email protected]" C
" : !#%
B+
-4 '(
+( '
@ W 4
W 4
$%"$As$0
;L" " ;H" ;" @'" ;" ;L'" ;" 5H2" > !A0$% + ) ^
) '
+
)=
%##"A#s##
;L" ;" '"
4
#)"AsA
!##% 9* +
+( * ' '
;L" ;" 4L'" 5" W" P" C+" :6" '" !AA0% '
@
/
44
%"
0$sA
;L";"5
"@"4L'"5"K">"L'"T" C+":6"5H2">"
'" !AAA% 9*
'* ' '
@
-))"&As?A
;L";"T'" "-"C" +("!##%@
(
C:75L M/[email protected] )
9-'' [email protected]
()
/=W#,"$?0s$$0
;L'" >" ;L" 4" 4L2" T" ;
'" " ;" " 5" :>"
:(+">";)""T
"T"L
";"!##% '
(
('+()'(
BB4B''
%%"&As?##
;L" 4" ;L'" >" ;
(
L" ;" ;H'" ;" L
" ;" TL2" C" 8" "
T''
""9"M:" 8L"C"!##?%9*@
[email protected]
''
+
'
4-=
+"?&s?
;+ " C" " " =" 54" C" /" " W" 6" " /'"
"*
"@"'
"!##A%@''+
'
+
) ') /& ' )
)
2
+
WM
+$"A$$sA$0&
;'
"!#%/'
'
'H
(
--##"&s&
;'
""@" "-">">"P""6B" ">"-
"@"K+""
6
'"- "9
""!AAA%9*'(
''+"
"69B
'
)+-))"$s0#
;" " " ;" L'" T" C'" " T
" ;" " " '8" ;
!#% B
8
) 8+ '
4
&++"
&s#
;2('" >" T
" T" " 5" " CW" 5H2" > !##% :
'
?= *@ ' H
' '
( + W
4
W 4
$,"$#As$#?#
;(
" C" >
" @" >" --K !##% 4
)
2
L '
)
+ >> >/ : 2M/65:7C:*
):'&"$s0
;" ;" " C4" C
'H" M:" :
" / !##A% - '
")"
9
[email protected] O @%,'"?&$s??
;)""8
)";":
+"5":
+
"-:!##&%
'8
''+ ' ' @@ 9
9+ 9
%&"
$$s0?
;
'"4"=""=2"9";""M":"5
"-"6'"5"
=+>(
+" !##A% 9
H ( 8 + )
))
W9
'9
+
=)'"#s#0
;>B4 4" :>" 6:@T" > !A&&% ; ' ' +'
(=W-)"&As&A
&
;";M";
')
"4">
""5
"@"=
("/"5H
" ">
""
("^"
" T" -
" !#% B
) ;9: F/:6
''
'F)
)'
9A9^[email protected]
;" " 5
" -" M" :" ;
'" 4" ;" /" 9" " M
" "
6'" 5" =+>(
+" !##?% @ ' 2 M/65?& + '
(
8
('
)( ' W -
: W -
: %%%" &s
?
;" " ;
'" 4" " " '" " 5
" -" " =" 6'" 5" =+>(
+" !##$% +
H
( 8
F ))
)
( + =
5 -' $*"
0#?s0
;
" M" " M" 9
" 5" :
" @" 9
" 5" 4
" " " " 5
"5"9
"6!#%-'
'
F
))22
8
[email protected] /[email protected]' /*=
#("s
;
'
"/" ""C'
"K ""6"@L"9C"58
""@
"
-" 5
" 9" K" 9T" 9
L" :" !#% 6
+
' +(FL
t+
u)8
'
-:
(%"As0
;
" T" -" 9" >
" 9C" @)" : " " " ;'" K" " " 9L" >K" =L" !##$% = :" :" :
) :
6;9 '
+8'8
*=
'W=
-'#+#"$&s$
;
Mh88"W"6"@"5" "=L"W"M49'"5'"-"-" "
/"[email protected]"K"=!##% '
*
)
))-("$s
;
(
L" ;" CL" > !##$% '
)
' @)
/*=
',,"#As$
;
(
L" ;" P" >" C'
" @" ;L" 4" T+L" " >" C" >
" " CL" > !##% 6 '(
)
' +( '?
)4-=
'"#s
;
(
L";"P">"C'
"@";L"4" "5"C'"W"@
L"C"T+L"
" >
" " 5H2" >" !##+% '? '
" 9*@" 2 L )
2
(6)%+"&s$
;
(
L" ;" T
" W" '
" ;" P" >" C'
" @" >
" " CL" >
!##&%[email protected]:9
'@'*
44
+"$s
$A
;" ; " :+
" /" -'" :" W
" " -" " ;)" " >" :"
6(" " C
L" @ !##A% '
+
'
-4 4&'#"#?&s#?A
;M" >" @)
" /" =n" -" " 4" " !#% ) '
7; ''
) *@7
')(/WB''
&%"&s?
;
""-
'
"9!##% '
F
))
24:)-#"0As##
?
;">>"":>!##%6'
+(*
;
4
#*"$s$&Q
$&s$?
O"T"'";" L"T" 8L">"T" "T'"4"4L'"5";L"
C" B" T" L
+" C" !##&% '
@ ' ) -L& 6 C+ (
-:9F '
''
(
''(*
@8'6-)
-
%,"?&s$A
O" >" ;" " T
L
'8
" ;" '8" ; !##% 9*@ *=
( (
' ' =
' =
( : -
'' $,," A$s
A
M'+""-2"9;"@
"CB" 28"W9"Cn"B"@"/"-)"5"
4
'" W-" >'" W" =
" 5" !##A% 4
76B9- &+
9
=
("&
MC
"-K"W
"@"9'"="4"="='(">"("W!##$%
+
+
=
'9
[email protected] O
@%,&"?&s?&$
M)8" 9W" P" " =H" " -" :" *" 4C" :+" @" ;"
W=" =H" C !##% *
' +
'
:%,"#?$s#$
ML" :6K" >
(" [email protected]" 9
'" /" K" M" e" T" KL
" " " -:"
" " 6
+" ;" )" W9" !##% B ' ( (
)+(
+
'8+(+
'965:@"B>"/65:"
45--%("A0s#
M
)"@"6":":(
"[email protected]!##?%='
'4:)-'"
&s?
M" B:" K
" @ !##% ; + 2 '
#)&"AAs#
M" W" 28" e" :+" - !##$% ) ' 4:9 ))-'+/%$&"0s0
M" " " ^" P
" 6" P" =" 5" 6 !AA0% 6B9-" 9P '
"(2-'
:6 [email protected]
[email protected] O @)*"#s&
K'("C/"-">W!##?%@*
()
'F
2(
*p4
:)W=4
+
4
9((%#"A0s#A
K'("C/">"9>"-""-">W!##0%9*@*@
'
('
+
)=
$%*"0s
&0
KL'
" >" @
(" " 4L('" ;" 4'" 6" T''
" " ;'L" " >L2" C !AA?% 9
C?$ + + B=
'
+
(2
(
'-(("$s0#
K+" W" -
K" " +" @" +(" " >" -> !AA%
C: 5" 2
) 2
W=
-'#')"?A00s?AA&
K" >" '" !AA$% = -:9 ' ' ' )
(
('W4
'')"?s?A
$
K""P">"K"9" L" "L
(("!##%4
'
) '+( 7) 2 '
W=
-'#(+"000s00?#
K" " L
((" " ^" ^ !##?% - ' :6 [email protected] )(
'
[email protected] /[email protected]' /*=
#,"&s&&
K""" C"C
H'";"^"^"C
)5":"/LL" -"L
(("
!##$%4
'
&7*
'
))9
#"?
K" " " ^" 9" " M" /" =+(" :" " /4 !##0% -
'
+( M/65 ( $ 9
[email protected] O @%,*"$$0s$$
K+" C" " W !AA?% -
) )
+
+ 2 +(''+
'
'
/=W%*"
&#s&$
K+"C"
"W!AA$%565:)
L
F
'
;6;B6%$"$0s0
K"W"="@"6
+"""T"-
"@"9L"-4"^
"
>" (" W" 5(" @=" :
" 6" !#% 4
* ('
)
(;"+
'
5
*i;W/*
#,)"$s$" K" >" " T" /" T" ;" W9T !##% 9*@'
@ ;
L
(
L
'W/*#,("AsA&$
K" -" :" -6" " " 9(" W" ;(" -W" ;+" W/" " "
>" -K" @" 5" M
" -" !##&% B
' +
2 2 )( +
+ 2 W
=
-'#+,"&$s?
K" " >" -" =
(" /" )" 9" )" :" KL" 9-" K" B:"
WffLf"W":'"P!##%@
'
(2+
+
' !=-4O% 2 !6 2% 2 '( ' ' 4
*"$As00
K("W "6("W"5"5"=)"@"-("5" 8"" '
":""K"
/)" =" C+" " !##&% )*
'
)
@9C'
=W-)$"s
KL" 6=" '+" =W" :
+'" W !##% M 2 ' '* + (
M/65!?&%M/65!%W=
-'#('"&&#s&&
K"C/"-+"W")" B"5+";"/)"K/"BL2" "5"W"T"^"
2" 4W" " 4W" !##&% ( )
565:+
@'W>'6('"?s?$
KL"K"9)"MC" -'+"-")="W"-"@5"-""
" K" K" " >
" " +" " !##% 9 BBB ( 8
' 2 ' ' +
' W - [email protected]' -
#+"?0s$
0
K'" "-"-"(""
2";"'"W" '":@" 28"=" '
)"
:" C(" !##?% )( )
' +F 'L +
4:)
)*"0&s0
K'"@"9
"6"@
" "="@";""9'"5";
'"W"
P"="+8L"-!##$% '
@5FL(('('
p=W4
%$,"&&s&?&
K
"K:">("9!#%;(
*(4:)- %%"
As#
K+"";'
""="W"-
'
"9"
""6
'"- !##%
; ''+ L 2 9* 2' '
*
4
$#"&s?
K""MLL
";""@@" )
("W"5'" ="-"-"M"@"L"
;" @
" C" L" @ !AAA% M 2 !M/65%L '
)4P+
M/65:
9
[email protected] O @)'"#$s
#$?
K
2HL" 6 !AA0% -
' )( (
W4
W 4
%+"?#s?#A
K
2HL"6!##%
(
'('
=W4
%#*"0sA
^" T" " 9" P" ^" K" W" 6" " K" T !#% 9
'
'
(
'9
+"&&
T)" " )" -" )" " 6" W" 8
" " =(=L
" "
@
(" [email protected]" )" 5" >" :" C" W" !#% 4
+
(;'
(;+))
W/*#,)"
$s$" sA
T''
" " 8L" C" L
" ;" " ;" ;L" 4" ;L'" >" 8" "
;""-
"@" "5"!##0%9*@)(;('
(
BB''
#,"s#
T'8L" T" ;
L" T" ;L" C" " ; !##&% B
+ L )
' ) 2 !M/655% +
L M/[email protected]?&=
'(!
%&&"00&0s00?
T" >" 9
" K" W" 6" " :" :" [email protected]" T" K" C
" B" =
>+"B"W
" ":"6W"!##A%B>B>'
'4/
W$',"$?&s$$
T" ^" " " T" " T
" W" L" @" 5
8" 6" 9" 4" >
" /" ;" e
!#% @ - *
) +
'
+(2*)'
9
[email protected] O @%,+"&As&A?
T
+" O"-
" " "O" W)" C" 6" P" T" " @
" ;" -
" T"
8+
"@";
" "!#%4
''
2+(
+
+'+('
'
)
'-:(#"#$s#&A
T" >" L(" W " =" =K" K" : " M" 6" )
)" :B" " W" -
"
[email protected]" =" W " 6
" K5 !##$% -
'
''+ $%*"0$s0
A
T
L" ";"-T"4)"6">"C">" 4"-+"@"-"@""->
!##?% ; )+ ''+ ' 4 )
)(
-=
#'"?&A0s??#0
T" >>" >
" -" " -= !##% -
'+(
*
8+
6/*96/9&"$s$0
P8""L(
)"T"""@"@"/(""8""T">"M
"/="
42
'+" /K !##?% >(
*+ M/65 -^-: +
'F '
' )
+ B) W ;
9
+'"s
P"T" "C""C:"""="W"T
"T"/"[email protected]
!##A% ;-' )
* " ) L)=
$#*"0sA
P
"^"-""^"e""T!##$%v/*
9*@
'
2'
wP
K-KCPP
-W6
%,"?&s?0
P
" 5^" -
" W" :" K9" =" @;" /'" !###% B
(
+
)
''+
4 =
("&s?#
P
" 5^" " >W" =" @;" /'" !##% 9
)
(''+9
[email protected] O @)+"&#s&&
P" W" -'" -M" C'" " '
L" " " ;@" " => !##$%
:' + + ''+ * =
%%,"$&s0
P
" ":"M"">"*" @"=
"5"5++
9("9"="
5" C" -" 5++
" " 5=" " !#% v5 + '
+F
#"### " ' w 4
*+"s
M P2" =" >'
" @W-6" " K9W" =+" W9>" =" >6"
9+" 6K" M =
L
)" > !##% 9/^B4" ) * '( ''+" * ) ' )
(' '
'+(
)([email protected]'@
@##*"?s
P('" ;" 6(" -" =
" W" " C" 5(" C" " 9-" >2" "
C2" @" =" >6" @
" " !#% '
9* '
)M/65
(
5)-#%"#s
#
Документ
Категория
Без категории
Просмотров
9
Размер файла
7 964 Кб
Теги
1/--страниц
Пожаловаться на содержимое документа