WWW.EL.Z-PDF.RU
БИБЛИОТЕКА  БЕСПЛАТНЫХ  МАТЕРИАЛОВ - Онлайн документы
 

Pages:     | 1 | 2 || 4 | 5 |   ...   | 15 |

«Антипролиферативное действие карнозина и его производных на опухолевые клетки нейрального происхождения ...»

-- [ Страница 3 ] --

ZD48a2V5d29yZD5PeHlnZW48L2tleXdvcmQ+PGtleXdvcmQ+UGVudG9zZXBob3NwaGF0ZXMvbWV0

YWJvbGlzbTwva2V5d29yZD48a2V5d29yZD5QZXJveGlkYXNlcy9tZXRhYm9saXNtPC9rZXl3b3Jk

PjxrZXl3b3JkPlBoYWdvY3l0b3Npczwva2V5d29yZD48a2V5d29yZD5SYXRzPC9rZXl3b3JkPjxr

ZXl3b3JkPlN1cGVyb3hpZGUgRGlzbXV0YXNlL21ldGFib2xpc208L2tleXdvcmQ+PC9rZXl3b3Jk

cz48ZGF0ZXM+PHllYXI+MTk3OTwveWVhcj48cHViLWRhdGVzPjxkYXRlPkp1bDwvZGF0ZT48L3B1

Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjAwMzEtOTMzMyAoUHJpbnQpJiN4RDswMDMxLTkzMzMgKExp

bmtpbmcpPC9pc2JuPjxhY2Nlc3Npb24tbnVtPjM3NTMyPC9hY2Nlc3Npb24tbnVtPjx1cmxzPjwv

dXJscz48cmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPk5MTTwvcmVtb3RlLWRhdGFiYXNlLXByb3Zp

ZGVyPjxsYW5ndWFnZT5lbmc8L2xhbmd1YWdlPjwvcmVjb3JkPjwvQ2l0ZT48L0VuZE5vdGU+

ADDIN EN.CITE.DATA [58, 59] или в цитоплазме с помощью глутатионпероксидазы (GPx) (H2O2 + 2GSH 2H2O + GSSG). Причем, GPx катализирует реакцию не только с H2O2, но и с ROOH приводя к образованию спиртов (ROH) PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NaWxsczwvQXV0aG9yPjxZZWFyPjE5NTc8L1llYXI+PFJl

Y051bT4yMDY8L1JlY051bT48RGlzcGxheVRleHQ+WzYwLCA2MV08L0Rpc3BsYXlUZXh0PjxyZWNv

cmQ+PHJlYy1udW1iZXI+MjA2PC9yZWMtbnVtYmVyPjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVO

IiBkYi1pZD0idzJ3ZnhhZmU2dmE5ejVlZXYybDU1YWE4c3hzYTU5OWVldjJzIj4yMDY8L2tleT48

L2ZvcmVpZ24ta2V5cz48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5

cGU+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPk1pbGxzLCBHLiBDLjwvYXV0aG9yPjwv

YXV0aG9ycz48L2NvbnRyaWJ1dG9ycz48dGl0bGVzPjx0aXRsZT5IZW1vZ2xvYmluIGNhdGFib2xp



c20uIEkuIEdsdXRhdGhpb25lIHBlcm94aWRhc2UsIGFuIGVyeXRocm9jeXRlIGVuenltZSB3aGlj

aCBwcm90ZWN0cyBoZW1vZ2xvYmluIGZyb20gb3hpZGF0aXZlIGJyZWFrZG93bjwvdGl0bGU+PHNl

Y29uZGFyeS10aXRsZT5KIEJpb2wgQ2hlbTwvc2Vjb25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+VGhl

IEpvdXJuYWwgb2YgYmlvbG9naWNhbCBjaGVtaXN0cnk8L2FsdC10aXRsZT48L3RpdGxlcz48cGVy

aW9kaWNhbD48ZnVsbC10aXRsZT5KIEJpb2wgQ2hlbTwvZnVsbC10aXRsZT48YWJici0xPlRoZSBK

b3VybmFsIG9mIGJpb2xvZ2ljYWwgY2hlbWlzdHJ5PC9hYmJyLTE+PC9wZXJpb2RpY2FsPjxhbHQt

cGVyaW9kaWNhbD48ZnVsbC10aXRsZT5KIEJpb2wgQ2hlbTwvZnVsbC10aXRsZT48YWJici0xPlRo

ZSBKb3VybmFsIG9mIGJpb2xvZ2ljYWwgY2hlbWlzdHJ5PC9hYmJyLTE+PC9hbHQtcGVyaW9kaWNh

bD48cGFnZXM+MTg5LTk3PC9wYWdlcz48dm9sdW1lPjIyOTwvdm9sdW1lPjxudW1iZXI+MTwvbnVt

YmVyPjxlZGl0aW9uPjE5NTcvMTEvMDE8L2VkaXRpb24+PGtleXdvcmRzPjxrZXl3b3JkPkhlbW9n

bG9iaW5zLyBtZXRhYm9saXNtPC9rZXl3b3JkPjxrZXl3b3JkPk94aWRvcmVkdWN0YXNlcy8gYmxv

b2Q8L2tleXdvcmQ+PC9rZXl3b3Jkcz48ZGF0ZXM+PHllYXI+MTk1NzwveWVhcj48cHViLWRhdGVz

PjxkYXRlPk5vdjwvZGF0ZT48L3B1Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjAwMjEtOTI1OCAoUHJp

bnQpJiN4RDswMDIxLTkyNTggKExpbmtpbmcpPC9pc2JuPjxhY2Nlc3Npb24tbnVtPjEzNDkxNTcz

PC9hY2Nlc3Npb24tbnVtPjx1cmxzPjwvdXJscz48cmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPk5M

TTwvcmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPjxsYW5ndWFnZT5lbmc8L2xhbmd1YWdlPjwvcmVj

b3JkPjwvQ2l0ZT48Q2l0ZT48QXV0aG9yPkNvaGVuPC9BdXRob3I+PFllYXI+MTk2MzwvWWVhcj48

UmVjTnVtPjIwNTwvUmVjTnVtPjxyZWNvcmQ+PHJlYy1udW1iZXI+MjA1PC9yZWMtbnVtYmVyPjxm

b3JlaWduLWtleXM+PGtleSBhcHA9IkVOIiBkYi1pZD0idzJ3ZnhhZmU2dmE5ejVlZXYybDU1YWE4

c3hzYTU5OWVldjJzIj4yMDU8L2tleT48L2ZvcmVpZ24ta2V5cz48cmVmLXR5cGUgbmFtZT0iSm91

cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9y

PkNvaGVuLCBHLjwvYXV0aG9yPjxhdXRob3I+SG9jaHN0ZWluLCBQLjwvYXV0aG9yPjwvYXV0aG9y

cz48L2NvbnRyaWJ1dG9ycz48dGl0bGVzPjx0aXRsZT5HTFVUQVRISU9ORSBQRVJPWElEQVNFOiBU

SEUgUFJJTUFSWSBBR0VOVCBGT1IgVEhFIEVMSU1JTkFUSU9OIE9GIEhZRFJPR0VOIFBFUk9YSURF





IElOIEVSWVRIUk9DWVRFUzwvdGl0bGU+PHNlY29uZGFyeS10aXRsZT5CaW9jaGVtaXN0cnk8L3Nl

Y29uZGFyeS10aXRsZT48YWx0LXRpdGxlPkJpb2NoZW1pc3RyeTwvYWx0LXRpdGxlPjwvdGl0bGVz

PjxwZXJpb2RpY2FsPjxmdWxsLXRpdGxlPkJpb2NoZW1pc3RyeTwvZnVsbC10aXRsZT48YWJici0x

PkJpb2NoZW1pc3RyeTwvYWJici0xPjwvcGVyaW9kaWNhbD48YWx0LXBlcmlvZGljYWw+PGZ1bGwt

dGl0bGU+QmlvY2hlbWlzdHJ5PC9mdWxsLXRpdGxlPjxhYmJyLTE+QmlvY2hlbWlzdHJ5PC9hYmJy

LTE+PC9hbHQtcGVyaW9kaWNhbD48cGFnZXM+MTQyMC04PC9wYWdlcz48dm9sdW1lPjI8L3ZvbHVt

ZT48ZWRpdGlvbj4xOTYzLzExLzAxPC9lZGl0aW9uPjxrZXl3b3Jkcz48a2V5d29yZD5DYXRhbGFz

ZTwva2V5d29yZD48a2V5d29yZD5Fcnl0aHJvY3l0ZXM8L2tleXdvcmQ+PGtleXdvcmQ+R2x1dGF0

aGlvbmU8L2tleXdvcmQ+PGtleXdvcmQ+SGVtb2x5c2lzPC9rZXl3b3JkPjxrZXl3b3JkPkh5ZHJv

Z2VuIFBlcm94aWRlPC9rZXl3b3JkPjxrZXl3b3JkPk1ldGFib2xpc208L2tleXdvcmQ+PGtleXdv

cmQ+TWV0aGVtb2dsb2Jpbjwva2V5d29yZD48a2V5d29yZD5QZXJveGlkYXNlczwva2V5d29yZD48

a2V5d29yZD5Qb3VsdHJ5PC9rZXl3b3JkPjxrZXl3b3JkPlJlc2VhcmNoPC9rZXl3b3JkPjwva2V5

d29yZHM+PGRhdGVzPjx5ZWFyPjE5NjM8L3llYXI+PHB1Yi1kYXRlcz48ZGF0ZT5Ob3YtRGVjPC9k

YXRlPjwvcHViLWRhdGVzPjwvZGF0ZXM+PGlzYm4+MDAwNi0yOTYwIChQcmludCkmI3hEOzAwMDYt

Mjk2MCAoTGlua2luZyk8L2lzYm4+PGFjY2Vzc2lvbi1udW0+MTQwOTM5MjA8L2FjY2Vzc2lvbi1u

dW0+PHVybHM+PC91cmxzPjxyZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+TkxNPC9yZW1vdGUtZGF0

YWJhc2UtcHJvdmlkZXI+PGxhbmd1YWdlPmVuZzwvbGFuZ3VhZ2U+PC9yZWNvcmQ+PC9DaXRlPjwv

RW5kTm90ZT5=

ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NaWxsczwvQXV0aG9yPjxZZWFyPjE5NTc8L1llYXI+PFJl

Y051bT4yMDY8L1JlY051bT48RGlzcGxheVRleHQ+WzYwLCA2MV08L0Rpc3BsYXlUZXh0PjxyZWNv

cmQ+PHJlYy1udW1iZXI+MjA2PC9yZWMtbnVtYmVyPjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVO

IiBkYi1pZD0idzJ3ZnhhZmU2dmE5ejVlZXYybDU1YWE4c3hzYTU5OWVldjJzIj4yMDY8L2tleT48

L2ZvcmVpZ24ta2V5cz48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5

cGU+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPk1pbGxzLCBHLiBDLjwvYXV0aG9yPjwv

YXV0aG9ycz48L2NvbnRyaWJ1dG9ycz48dGl0bGVzPjx0aXRsZT5IZW1vZ2xvYmluIGNhdGFib2xp



c20uIEkuIEdsdXRhdGhpb25lIHBlcm94aWRhc2UsIGFuIGVyeXRocm9jeXRlIGVuenltZSB3aGlj

aCBwcm90ZWN0cyBoZW1vZ2xvYmluIGZyb20gb3hpZGF0aXZlIGJyZWFrZG93bjwvdGl0bGU+PHNl

Y29uZGFyeS10aXRsZT5KIEJpb2wgQ2hlbTwvc2Vjb25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+VGhl

IEpvdXJuYWwgb2YgYmlvbG9naWNhbCBjaGVtaXN0cnk8L2FsdC10aXRsZT48L3RpdGxlcz48cGVy

aW9kaWNhbD48ZnVsbC10aXRsZT5KIEJpb2wgQ2hlbTwvZnVsbC10aXRsZT48YWJici0xPlRoZSBK

b3VybmFsIG9mIGJpb2xvZ2ljYWwgY2hlbWlzdHJ5PC9hYmJyLTE+PC9wZXJpb2RpY2FsPjxhbHQt

cGVyaW9kaWNhbD48ZnVsbC10aXRsZT5KIEJpb2wgQ2hlbTwvZnVsbC10aXRsZT48YWJici0xPlRo

ZSBKb3VybmFsIG9mIGJpb2xvZ2ljYWwgY2hlbWlzdHJ5PC9hYmJyLTE+PC9hbHQtcGVyaW9kaWNh

bD48cGFnZXM+MTg5LTk3PC9wYWdlcz48dm9sdW1lPjIyOTwvdm9sdW1lPjxudW1iZXI+MTwvbnVt

YmVyPjxlZGl0aW9uPjE5NTcvMTEvMDE8L2VkaXRpb24+PGtleXdvcmRzPjxrZXl3b3JkPkhlbW9n

bG9iaW5zLyBtZXRhYm9saXNtPC9rZXl3b3JkPjxrZXl3b3JkPk94aWRvcmVkdWN0YXNlcy8gYmxv

b2Q8L2tleXdvcmQ+PC9rZXl3b3Jkcz48ZGF0ZXM+PHllYXI+MTk1NzwveWVhcj48cHViLWRhdGVz

PjxkYXRlPk5vdjwvZGF0ZT48L3B1Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjAwMjEtOTI1OCAoUHJp

bnQpJiN4RDswMDIxLTkyNTggKExpbmtpbmcpPC9pc2JuPjxhY2Nlc3Npb24tbnVtPjEzNDkxNTcz

PC9hY2Nlc3Npb24tbnVtPjx1cmxzPjwvdXJscz48cmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPk5M

TTwvcmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPjxsYW5ndWFnZT5lbmc8L2xhbmd1YWdlPjwvcmVj

b3JkPjwvQ2l0ZT48Q2l0ZT48QXV0aG9yPkNvaGVuPC9BdXRob3I+PFllYXI+MTk2MzwvWWVhcj48

UmVjTnVtPjIwNTwvUmVjTnVtPjxyZWNvcmQ+PHJlYy1udW1iZXI+MjA1PC9yZWMtbnVtYmVyPjxm

b3JlaWduLWtleXM+PGtleSBhcHA9IkVOIiBkYi1pZD0idzJ3ZnhhZmU2dmE5ejVlZXYybDU1YWE4

c3hzYTU5OWVldjJzIj4yMDU8L2tleT48L2ZvcmVpZ24ta2V5cz48cmVmLXR5cGUgbmFtZT0iSm91

cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9y

PkNvaGVuLCBHLjwvYXV0aG9yPjxhdXRob3I+SG9jaHN0ZWluLCBQLjwvYXV0aG9yPjwvYXV0aG9y

cz48L2NvbnRyaWJ1dG9ycz48dGl0bGVzPjx0aXRsZT5HTFVUQVRISU9ORSBQRVJPWElEQVNFOiBU

SEUgUFJJTUFSWSBBR0VOVCBGT1IgVEhFIEVMSU1JTkFUSU9OIE9GIEhZRFJPR0VOIFBFUk9YSURF





IElOIEVSWVRIUk9DWVRFUzwvdGl0bGU+PHNlY29uZGFyeS10aXRsZT5CaW9jaGVtaXN0cnk8L3Nl

Y29uZGFyeS10aXRsZT48YWx0LXRpdGxlPkJpb2NoZW1pc3RyeTwvYWx0LXRpdGxlPjwvdGl0bGVz

PjxwZXJpb2RpY2FsPjxmdWxsLXRpdGxlPkJpb2NoZW1pc3RyeTwvZnVsbC10aXRsZT48YWJici0x

PkJpb2NoZW1pc3RyeTwvYWJici0xPjwvcGVyaW9kaWNhbD48YWx0LXBlcmlvZGljYWw+PGZ1bGwt

dGl0bGU+QmlvY2hlbWlzdHJ5PC9mdWxsLXRpdGxlPjxhYmJyLTE+QmlvY2hlbWlzdHJ5PC9hYmJy

LTE+PC9hbHQtcGVyaW9kaWNhbD48cGFnZXM+MTQyMC04PC9wYWdlcz48dm9sdW1lPjI8L3ZvbHVt

ZT48ZWRpdGlvbj4xOTYzLzExLzAxPC9lZGl0aW9uPjxrZXl3b3Jkcz48a2V5d29yZD5DYXRhbGFz

ZTwva2V5d29yZD48a2V5d29yZD5Fcnl0aHJvY3l0ZXM8L2tleXdvcmQ+PGtleXdvcmQ+R2x1dGF0

aGlvbmU8L2tleXdvcmQ+PGtleXdvcmQ+SGVtb2x5c2lzPC9rZXl3b3JkPjxrZXl3b3JkPkh5ZHJv

Z2VuIFBlcm94aWRlPC9rZXl3b3JkPjxrZXl3b3JkPk1ldGFib2xpc208L2tleXdvcmQ+PGtleXdv

cmQ+TWV0aGVtb2dsb2Jpbjwva2V5d29yZD48a2V5d29yZD5QZXJveGlkYXNlczwva2V5d29yZD48

a2V5d29yZD5Qb3VsdHJ5PC9rZXl3b3JkPjxrZXl3b3JkPlJlc2VhcmNoPC9rZXl3b3JkPjwva2V5

d29yZHM+PGRhdGVzPjx5ZWFyPjE5NjM8L3llYXI+PHB1Yi1kYXRlcz48ZGF0ZT5Ob3YtRGVjPC9k

YXRlPjwvcHViLWRhdGVzPjwvZGF0ZXM+PGlzYm4+MDAwNi0yOTYwIChQcmludCkmI3hEOzAwMDYt

Mjk2MCAoTGlua2luZyk8L2lzYm4+PGFjY2Vzc2lvbi1udW0+MTQwOTM5MjA8L2FjY2Vzc2lvbi1u

dW0+PHVybHM+PC91cmxzPjxyZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+TkxNPC9yZW1vdGUtZGF0

YWJhc2UtcHJvdmlkZXI+PGxhbmd1YWdlPmVuZzwvbGFuZ3VhZ2U+PC9yZWNvcmQ+PC9DaXRlPjwv

RW5kTm90ZT5=

ADDIN EN.CITE.DATA [60, 61].

Благодаря способности модулировать внутриклеточный уровень АФК антиоксиданты способны влиять на пролиферацию клеток. Как было отмечено выше (см. 1.1.1), в небольших количествах АФК индуцируют пролиферацию клеток. Снижение уровня Н2О2 за счет усиления экспрессии каталазы в эндотелиальных клетках и HER-2/Neu-трансформированных Rat-1 фибробластах приводило к ингибированию пролиферации этих клеток PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5aYW5ldHRpPC9BdXRob3I+PFllYXI+MjAwMjwvWWVhcj48

UmVjTnVtPjQ1OTwvUmVjTnVtPjxEaXNwbGF5VGV4dD5bNjIsIDYzXTwvRGlzcGxheVRleHQ+PHJl

Y29yZD48cmVjLW51bWJlcj40NTk8L3JlYy1udW1iZXI+PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0i

RU4iIGRiLWlkPSJ3MndmeGFmZTZ2YTl6NWVldjJsNTVhYThzeHNhNTk5ZWV2MnMiPjQ1OTwva2V5

PjwvZm9yZWlnbi1rZXlzPjxyZWYtdHlwZSBuYW1lPSJKb3VybmFsIEFydGljbGUiPjE3PC9yZWYt

dHlwZT48Y29udHJpYnV0b3JzPjxhdXRob3JzPjxhdXRob3I+WmFuZXR0aSwgTS48L2F1dGhvcj48

YXV0aG9yPkthdHVzaWMsIFouIFMuPC9hdXRob3I+PGF1dGhvcj5PJmFwb3M7QnJpZW4sIFQuPC9h

dXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjxhdXRoLWFkZHJlc3M+RGVwYXJ0bWVudCBv

ZiBFbmRvY3Jpbm9sb2d5LCBNYXlvIENsaW5pYyBhbmQgRm91bmRhdGlvbiwgUm9jaGVzdGVyLCBN

aW5uZXNvdGEgNTU5MDUsIFVTQS48L2F1dGgtYWRkcmVzcz48dGl0bGVzPjx0aXRsZT5BZGVub3Zp

cmFsLW1lZGlhdGVkIG92ZXJleHByZXNzaW9uIG9mIGNhdGFsYXNlIGluaGliaXRzIGVuZG90aGVs

aWFsIGNlbGwgcHJvbGlmZXJhdGlvbjwvdGl0bGU+PHNlY29uZGFyeS10aXRsZT5BbSBKIFBoeXNp

b2wgSGVhcnQgQ2lyYyBQaHlzaW9sPC9zZWNvbmRhcnktdGl0bGU+PGFsdC10aXRsZT5BbWVyaWNh

biBqb3VybmFsIG9mIHBoeXNpb2xvZ3kuIEhlYXJ0IGFuZCBjaXJjdWxhdG9yeSBwaHlzaW9sb2d5

PC9hbHQtdGl0bGU+PC90aXRsZXM+PHBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+QW0gSiBQaHlzaW9s

IEhlYXJ0IENpcmMgUGh5c2lvbDwvZnVsbC10aXRsZT48YWJici0xPkFtZXJpY2FuIGpvdXJuYWwg

b2YgcGh5c2lvbG9neS4gSGVhcnQgYW5kIGNpcmN1bGF0b3J5IHBoeXNpb2xvZ3k8L2FiYnItMT48

L3BlcmlvZGljYWw+PGFsdC1wZXJpb2RpY2FsPjxmdWxsLXRpdGxlPkFtIEogUGh5c2lvbCBIZWFy

dCBDaXJjIFBoeXNpb2w8L2Z1bGwtdGl0bGU+PGFiYnItMT5BbWVyaWNhbiBqb3VybmFsIG9mIHBo

eXNpb2xvZ3kuIEhlYXJ0IGFuZCBjaXJjdWxhdG9yeSBwaHlzaW9sb2d5PC9hYmJyLTE+PC9hbHQt

cGVyaW9kaWNhbD48cGFnZXM+SDI2MjAtNjwvcGFnZXM+PHZvbHVtZT4yODM8L3ZvbHVtZT48bnVt

YmVyPjY8L251bWJlcj48ZWRpdGlvbj4yMDAyLzExLzEzPC9lZGl0aW9uPjxrZXl3b3Jkcz48a2V5

d29yZD5BZGVub3ZpcmlkYWUvIGdlbmV0aWNzPC9rZXl3b3JkPjxrZXl3b3JkPkFwb3B0b3Npczwv

a2V5d29yZD48a2V5d29yZD5CbG90dGluZywgV2VzdGVybjwva2V5d29yZD48a2V5d29yZD5DYXRh

bGFzZS8gYmlvc3ludGhlc2lzL2dlbmV0aWNzPC9rZXl3b3JkPjxrZXl3b3JkPkNlbGwgRGl2aXNp

b24vcGh5c2lvbG9neTwva2V5d29yZD48a2V5d29yZD5DZWxsIExpbmU8L2tleXdvcmQ+PGtleXdv

cmQ+RE5BL2Jpb3N5bnRoZXNpczwva2V5d29yZD48a2V5d29yZD5FbmRvdGhlbGl1bSwgVmFzY3Vs

YXIvY3l0b2xvZ3kvIG1ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+RW56eW1lIEFjdGl2YXRp

b24vcGh5c2lvbG9neTwva2V5d29yZD48a2V5d29yZD5HZW5lIEV4cHJlc3Npb24vIHBoeXNpb2xv

Z3k8L2tleXdvcmQ+PGtleXdvcmQ+SHVtYW5zPC9rZXl3b3JkPjxrZXl3b3JkPkh5ZHJvZ2VuIFBl

cm94aWRlL21ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+T3hpZGFudHMvbWV0YWJvbGlzbTwv

a2V5d29yZD48a2V5d29yZD5UcmFuc2R1Y3Rpb24sIEdlbmV0aWM8L2tleXdvcmQ+PC9rZXl3b3Jk

cz48ZGF0ZXM+PHllYXI+MjAwMjwveWVhcj48cHViLWRhdGVzPjxkYXRlPkRlYzwvZGF0ZT48L3B1

Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjAzNjMtNjEzNSAoUHJpbnQpJiN4RDswMzYzLTYxMzUgKExp

bmtpbmcpPC9pc2JuPjxhY2Nlc3Npb24tbnVtPjEyNDI3NjAxPC9hY2Nlc3Npb24tbnVtPjx1cmxz

PjwvdXJscz48ZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+MTAuMTE1Mi9hanBoZWFydC4wMDM1OC4y

MDAxPC9lbGVjdHJvbmljLXJlc291cmNlLW51bT48cmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPk5M

TTwvcmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPjxsYW5ndWFnZT5lbmc8L2xhbmd1YWdlPjwvcmVj

b3JkPjwvQ2l0ZT48Q2l0ZT48QXV0aG9yPlByZXN0b248L0F1dGhvcj48WWVhcj4yMDAxPC9ZZWFy

PjxSZWNOdW0+NDYwPC9SZWNOdW0+PHJlY29yZD48cmVjLW51bWJlcj40NjA8L3JlYy1udW1iZXI+

PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0iRU4iIGRiLWlkPSJ3MndmeGFmZTZ2YTl6NWVldjJsNTVh

YThzeHNhNTk5ZWV2MnMiPjQ2MDwva2V5PjwvZm9yZWlnbi1rZXlzPjxyZWYtdHlwZSBuYW1lPSJK

b3VybmFsIEFydGljbGUiPjE3PC9yZWYtdHlwZT48Y29udHJpYnV0b3JzPjxhdXRob3JzPjxhdXRo

b3I+UHJlc3RvbiwgVC4gSi48L2F1dGhvcj48YXV0aG9yPk11bGxlciwgVy4gSi48L2F1dGhvcj48

YXV0aG9yPlNpbmdoLCBHLjwvYXV0aG9yPjwvYXV0aG9ycz48L2NvbnRyaWJ1dG9ycz48YXV0aC1h

ZGRyZXNzPkhhbWlsdG9uIFJlZ2lvbmFsIENhbmNlciBDZW50cmUgYW5kIERlcGFydG1lbnQgb2Yg

UGF0aG9sb2d5IGFuZCBNb2xlY3VsYXIgTWVkaWNpbmUsIEZhY3VsdHkgb2YgSGVhbHRoIFNjaWVu

Y2VzLCBNY01hc3RlciBVbml2ZXJzaXR5LCBIYW1pbHRvbiwgT250YXJpbyBMOFYgNUMyLCBDYW5h

ZGEuPC9hdXRoLWFkZHJlc3M+PHRpdGxlcz48dGl0bGU+U2NhdmVuZ2luZyBvZiBleHRyYWNlbGx1

bGFyIEgyTzIgYnkgY2F0YWxhc2UgaW5oaWJpdHMgdGhlIHByb2xpZmVyYXRpb24gb2YgSEVSLTIv

TmV1LXRyYW5zZm9ybWVkIHJhdC0xIGZpYnJvYmxhc3RzIHRocm91Z2ggdGhlIGluZHVjdGlvbiBv

ZiBhIHN0cmVzcyByZXNwb25zZTwvdGl0bGU+PHNlY29uZGFyeS10aXRsZT5KIEJpb2wgQ2hlbTwv

c2Vjb25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+VGhlIEpvdXJuYWwgb2YgYmlvbG9naWNhbCBjaGVt

aXN0cnk8L2FsdC10aXRsZT48L3RpdGxlcz48cGVyaW9kaWNhbD48ZnVsbC10aXRsZT5KIEJpb2wg

Q2hlbTwvZnVsbC10aXRsZT48YWJici0xPlRoZSBKb3VybmFsIG9mIGJpb2xvZ2ljYWwgY2hlbWlz

dHJ5PC9hYmJyLTE+PC9wZXJpb2RpY2FsPjxhbHQtcGVyaW9kaWNhbD48ZnVsbC10aXRsZT5KIEJp

b2wgQ2hlbTwvZnVsbC10aXRsZT48YWJici0xPlRoZSBKb3VybmFsIG9mIGJpb2xvZ2ljYWwgY2hl

bWlzdHJ5PC9hYmJyLTE+PC9hbHQtcGVyaW9kaWNhbD48cGFnZXM+OTU1OC02NDwvcGFnZXM+PHZv

bHVtZT4yNzY8L3ZvbHVtZT48bnVtYmVyPjEyPC9udW1iZXI+PGVkaXRpb24+MjAwMS8wMS8xMzwv

ZWRpdGlvbj48a2V5d29yZHM+PGtleXdvcmQ+QW5pbWFsczwva2V5d29yZD48a2V5d29yZD5DYXRh

bGFzZS8gbWV0YWJvbGlzbTwva2V5d29yZD48a2V5d29yZD5DZWxsIERpdmlzaW9uPC9rZXl3b3Jk

PjxrZXl3b3JkPkNlbGwgTGluZSwgVHJhbnNmb3JtZWQ8L2tleXdvcmQ+PGtleXdvcmQ+SHlkcm9n

ZW4gUGVyb3hpZGUvIG1ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+Sk5LIE1pdG9nZW4tQWN0

aXZhdGVkIFByb3RlaW4gS2luYXNlczwva2V5d29yZD48a2V5d29yZD5NaXRvZ2VuLUFjdGl2YXRl

ZCBQcm90ZWluIEtpbmFzZSAxL21ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+TWl0b2dlbi1B

Y3RpdmF0ZWQgUHJvdGVpbiBLaW5hc2UgMzwva2V5d29yZD48a2V5d29yZD5NaXRvZ2VuLUFjdGl2

YXRlZCBQcm90ZWluIEtpbmFzZXMvbWV0YWJvbGlzbTwva2V5d29yZD48a2V5d29yZD5PeGlkYXRp

dmUgU3RyZXNzPC9rZXl3b3JkPjxrZXl3b3JkPlBob3NwaG9yeWxhdGlvbjwva2V5d29yZD48a2V5

d29yZD5SYXRzPC9rZXl3b3JkPjxrZXl3b3JkPlJlY2VwdG9yLCBlcmJCLTIvcGh5c2lvbG9neTwv

a2V5d29yZD48L2tleXdvcmRzPjxkYXRlcz48eWVhcj4yMDAxPC95ZWFyPjxwdWItZGF0ZXM+PGRh

dGU+TWFyIDIzPC9kYXRlPjwvcHViLWRhdGVzPjwvZGF0ZXM+PGlzYm4+MDAyMS05MjU4IChQcmlu

dCkmI3hEOzAwMjEtOTI1OCAoTGlua2luZyk8L2lzYm4+PGFjY2Vzc2lvbi1udW0+MTExMzQwMDA8

L2FjY2Vzc2lvbi1udW0+PHVybHM+PC91cmxzPjxlbGVjdHJvbmljLXJlc291cmNlLW51bT4xMC4x

MDc0L2piYy5NMDA0NjE3MjAwPC9lbGVjdHJvbmljLXJlc291cmNlLW51bT48cmVtb3RlLWRhdGFi

YXNlLXByb3ZpZGVyPk5MTTwvcmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPjxsYW5ndWFnZT5lbmc8

L2xhbmd1YWdlPjwvcmVjb3JkPjwvQ2l0ZT48L0VuZE5vdGU+AG==

ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5aYW5ldHRpPC9BdXRob3I+PFllYXI+MjAwMjwvWWVhcj48

UmVjTnVtPjQ1OTwvUmVjTnVtPjxEaXNwbGF5VGV4dD5bNjIsIDYzXTwvRGlzcGxheVRleHQ+PHJl

Y29yZD48cmVjLW51bWJlcj40NTk8L3JlYy1udW1iZXI+PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0i

RU4iIGRiLWlkPSJ3MndmeGFmZTZ2YTl6NWVldjJsNTVhYThzeHNhNTk5ZWV2MnMiPjQ1OTwva2V5

PjwvZm9yZWlnbi1rZXlzPjxyZWYtdHlwZSBuYW1lPSJKb3VybmFsIEFydGljbGUiPjE3PC9yZWYt

dHlwZT48Y29udHJpYnV0b3JzPjxhdXRob3JzPjxhdXRob3I+WmFuZXR0aSwgTS48L2F1dGhvcj48

YXV0aG9yPkthdHVzaWMsIFouIFMuPC9hdXRob3I+PGF1dGhvcj5PJmFwb3M7QnJpZW4sIFQuPC9h

dXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjxhdXRoLWFkZHJlc3M+RGVwYXJ0bWVudCBv

ZiBFbmRvY3Jpbm9sb2d5LCBNYXlvIENsaW5pYyBhbmQgRm91bmRhdGlvbiwgUm9jaGVzdGVyLCBN

aW5uZXNvdGEgNTU5MDUsIFVTQS48L2F1dGgtYWRkcmVzcz48dGl0bGVzPjx0aXRsZT5BZGVub3Zp

cmFsLW1lZGlhdGVkIG92ZXJleHByZXNzaW9uIG9mIGNhdGFsYXNlIGluaGliaXRzIGVuZG90aGVs

aWFsIGNlbGwgcHJvbGlmZXJhdGlvbjwvdGl0bGU+PHNlY29uZGFyeS10aXRsZT5BbSBKIFBoeXNp

b2wgSGVhcnQgQ2lyYyBQaHlzaW9sPC9zZWNvbmRhcnktdGl0bGU+PGFsdC10aXRsZT5BbWVyaWNh

biBqb3VybmFsIG9mIHBoeXNpb2xvZ3kuIEhlYXJ0IGFuZCBjaXJjdWxhdG9yeSBwaHlzaW9sb2d5

PC9hbHQtdGl0bGU+PC90aXRsZXM+PHBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+QW0gSiBQaHlzaW9s

IEhlYXJ0IENpcmMgUGh5c2lvbDwvZnVsbC10aXRsZT48YWJici0xPkFtZXJpY2FuIGpvdXJuYWwg

b2YgcGh5c2lvbG9neS4gSGVhcnQgYW5kIGNpcmN1bGF0b3J5IHBoeXNpb2xvZ3k8L2FiYnItMT48

L3BlcmlvZGljYWw+PGFsdC1wZXJpb2RpY2FsPjxmdWxsLXRpdGxlPkFtIEogUGh5c2lvbCBIZWFy

dCBDaXJjIFBoeXNpb2w8L2Z1bGwtdGl0bGU+PGFiYnItMT5BbWVyaWNhbiBqb3VybmFsIG9mIHBo

eXNpb2xvZ3kuIEhlYXJ0IGFuZCBjaXJjdWxhdG9yeSBwaHlzaW9sb2d5PC9hYmJyLTE+PC9hbHQt

cGVyaW9kaWNhbD48cGFnZXM+SDI2MjAtNjwvcGFnZXM+PHZvbHVtZT4yODM8L3ZvbHVtZT48bnVt

YmVyPjY8L251bWJlcj48ZWRpdGlvbj4yMDAyLzExLzEzPC9lZGl0aW9uPjxrZXl3b3Jkcz48a2V5

d29yZD5BZGVub3ZpcmlkYWUvIGdlbmV0aWNzPC9rZXl3b3JkPjxrZXl3b3JkPkFwb3B0b3Npczwv

a2V5d29yZD48a2V5d29yZD5CbG90dGluZywgV2VzdGVybjwva2V5d29yZD48a2V5d29yZD5DYXRh

bGFzZS8gYmlvc3ludGhlc2lzL2dlbmV0aWNzPC9rZXl3b3JkPjxrZXl3b3JkPkNlbGwgRGl2aXNp

b24vcGh5c2lvbG9neTwva2V5d29yZD48a2V5d29yZD5DZWxsIExpbmU8L2tleXdvcmQ+PGtleXdv

cmQ+RE5BL2Jpb3N5bnRoZXNpczwva2V5d29yZD48a2V5d29yZD5FbmRvdGhlbGl1bSwgVmFzY3Vs

YXIvY3l0b2xvZ3kvIG1ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+RW56eW1lIEFjdGl2YXRp

b24vcGh5c2lvbG9neTwva2V5d29yZD48a2V5d29yZD5HZW5lIEV4cHJlc3Npb24vIHBoeXNpb2xv

Z3k8L2tleXdvcmQ+PGtleXdvcmQ+SHVtYW5zPC9rZXl3b3JkPjxrZXl3b3JkPkh5ZHJvZ2VuIFBl

cm94aWRlL21ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+T3hpZGFudHMvbWV0YWJvbGlzbTwv

a2V5d29yZD48a2V5d29yZD5UcmFuc2R1Y3Rpb24sIEdlbmV0aWM8L2tleXdvcmQ+PC9rZXl3b3Jk

cz48ZGF0ZXM+PHllYXI+MjAwMjwveWVhcj48cHViLWRhdGVzPjxkYXRlPkRlYzwvZGF0ZT48L3B1

Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjAzNjMtNjEzNSAoUHJpbnQpJiN4RDswMzYzLTYxMzUgKExp

bmtpbmcpPC9pc2JuPjxhY2Nlc3Npb24tbnVtPjEyNDI3NjAxPC9hY2Nlc3Npb24tbnVtPjx1cmxz

PjwvdXJscz48ZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+MTAuMTE1Mi9hanBoZWFydC4wMDM1OC4y

MDAxPC9lbGVjdHJvbmljLXJlc291cmNlLW51bT48cmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPk5M

TTwvcmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPjxsYW5ndWFnZT5lbmc8L2xhbmd1YWdlPjwvcmVj

b3JkPjwvQ2l0ZT48Q2l0ZT48QXV0aG9yPlByZXN0b248L0F1dGhvcj48WWVhcj4yMDAxPC9ZZWFy

PjxSZWNOdW0+NDYwPC9SZWNOdW0+PHJlY29yZD48cmVjLW51bWJlcj40NjA8L3JlYy1udW1iZXI+

PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0iRU4iIGRiLWlkPSJ3MndmeGFmZTZ2YTl6NWVldjJsNTVh

YThzeHNhNTk5ZWV2MnMiPjQ2MDwva2V5PjwvZm9yZWlnbi1rZXlzPjxyZWYtdHlwZSBuYW1lPSJK

b3VybmFsIEFydGljbGUiPjE3PC9yZWYtdHlwZT48Y29udHJpYnV0b3JzPjxhdXRob3JzPjxhdXRo

b3I+UHJlc3RvbiwgVC4gSi48L2F1dGhvcj48YXV0aG9yPk11bGxlciwgVy4gSi48L2F1dGhvcj48

YXV0aG9yPlNpbmdoLCBHLjwvYXV0aG9yPjwvYXV0aG9ycz48L2NvbnRyaWJ1dG9ycz48YXV0aC1h

ZGRyZXNzPkhhbWlsdG9uIFJlZ2lvbmFsIENhbmNlciBDZW50cmUgYW5kIERlcGFydG1lbnQgb2Yg

UGF0aG9sb2d5IGFuZCBNb2xlY3VsYXIgTWVkaWNpbmUsIEZhY3VsdHkgb2YgSGVhbHRoIFNjaWVu

Y2VzLCBNY01hc3RlciBVbml2ZXJzaXR5LCBIYW1pbHRvbiwgT250YXJpbyBMOFYgNUMyLCBDYW5h

ZGEuPC9hdXRoLWFkZHJlc3M+PHRpdGxlcz48dGl0bGU+U2NhdmVuZ2luZyBvZiBleHRyYWNlbGx1

bGFyIEgyTzIgYnkgY2F0YWxhc2UgaW5oaWJpdHMgdGhlIHByb2xpZmVyYXRpb24gb2YgSEVSLTIv

TmV1LXRyYW5zZm9ybWVkIHJhdC0xIGZpYnJvYmxhc3RzIHRocm91Z2ggdGhlIGluZHVjdGlvbiBv

ZiBhIHN0cmVzcyByZXNwb25zZTwvdGl0bGU+PHNlY29uZGFyeS10aXRsZT5KIEJpb2wgQ2hlbTwv

c2Vjb25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+VGhlIEpvdXJuYWwgb2YgYmlvbG9naWNhbCBjaGVt

aXN0cnk8L2FsdC10aXRsZT48L3RpdGxlcz48cGVyaW9kaWNhbD48ZnVsbC10aXRsZT5KIEJpb2wg

Q2hlbTwvZnVsbC10aXRsZT48YWJici0xPlRoZSBKb3VybmFsIG9mIGJpb2xvZ2ljYWwgY2hlbWlz

dHJ5PC9hYmJyLTE+PC9wZXJpb2RpY2FsPjxhbHQtcGVyaW9kaWNhbD48ZnVsbC10aXRsZT5KIEJp

b2wgQ2hlbTwvZnVsbC10aXRsZT48YWJici0xPlRoZSBKb3VybmFsIG9mIGJpb2xvZ2ljYWwgY2hl

bWlzdHJ5PC9hYmJyLTE+PC9hbHQtcGVyaW9kaWNhbD48cGFnZXM+OTU1OC02NDwvcGFnZXM+PHZv

bHVtZT4yNzY8L3ZvbHVtZT48bnVtYmVyPjEyPC9udW1iZXI+PGVkaXRpb24+MjAwMS8wMS8xMzwv

ZWRpdGlvbj48a2V5d29yZHM+PGtleXdvcmQ+QW5pbWFsczwva2V5d29yZD48a2V5d29yZD5DYXRh

bGFzZS8gbWV0YWJvbGlzbTwva2V5d29yZD48a2V5d29yZD5DZWxsIERpdmlzaW9uPC9rZXl3b3Jk

PjxrZXl3b3JkPkNlbGwgTGluZSwgVHJhbnNmb3JtZWQ8L2tleXdvcmQ+PGtleXdvcmQ+SHlkcm9n

ZW4gUGVyb3hpZGUvIG1ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+Sk5LIE1pdG9nZW4tQWN0

aXZhdGVkIFByb3RlaW4gS2luYXNlczwva2V5d29yZD48a2V5d29yZD5NaXRvZ2VuLUFjdGl2YXRl

ZCBQcm90ZWluIEtpbmFzZSAxL21ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+TWl0b2dlbi1B

Y3RpdmF0ZWQgUHJvdGVpbiBLaW5hc2UgMzwva2V5d29yZD48a2V5d29yZD5NaXRvZ2VuLUFjdGl2

YXRlZCBQcm90ZWluIEtpbmFzZXMvbWV0YWJvbGlzbTwva2V5d29yZD48a2V5d29yZD5PeGlkYXRp

dmUgU3RyZXNzPC9rZXl3b3JkPjxrZXl3b3JkPlBob3NwaG9yeWxhdGlvbjwva2V5d29yZD48a2V5

d29yZD5SYXRzPC9rZXl3b3JkPjxrZXl3b3JkPlJlY2VwdG9yLCBlcmJCLTIvcGh5c2lvbG9neTwv

a2V5d29yZD48L2tleXdvcmRzPjxkYXRlcz48eWVhcj4yMDAxPC95ZWFyPjxwdWItZGF0ZXM+PGRh

dGU+TWFyIDIzPC9kYXRlPjwvcHViLWRhdGVzPjwvZGF0ZXM+PGlzYm4+MDAyMS05MjU4IChQcmlu

dCkmI3hEOzAwMjEtOTI1OCAoTGlua2luZyk8L2lzYm4+PGFjY2Vzc2lvbi1udW0+MTExMzQwMDA8

L2FjY2Vzc2lvbi1udW0+PHVybHM+PC91cmxzPjxlbGVjdHJvbmljLXJlc291cmNlLW51bT4xMC4x

MDc0L2piYy5NMDA0NjE3MjAwPC9lbGVjdHJvbmljLXJlc291cmNlLW51bT48cmVtb3RlLWRhdGFi

YXNlLXByb3ZpZGVyPk5MTTwvcmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPjxsYW5ndWFnZT5lbmc8

L2xhbmd1YWdlPjwvcmVjb3JkPjwvQ2l0ZT48L0VuZE5vdGU+AG==

ADDIN EN.CITE.DATA [62, 63]. Понижение уровня АФК под действием синтетического антиоксиданта N-ацетил-цистеина (NAC) в клетках слизистой оболочки полости рта тажке приводило к замедлению пролиферативных процессов PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5OYXJnaTwvQXV0aG9yPjxZZWFyPjE5OTk8L1llYXI+PFJl

Y051bT40NjE8L1JlY051bT48RGlzcGxheVRleHQ+WzY0LCA2NV08L0Rpc3BsYXlUZXh0PjxyZWNv

cmQ+PHJlYy1udW1iZXI+NDYxPC9yZWMtbnVtYmVyPjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVO

IiBkYi1pZD0idzJ3ZnhhZmU2dmE5ejVlZXYybDU1YWE4c3hzYTU5OWVldjJzIj40NjE8L2tleT48

L2ZvcmVpZ24ta2V5cz48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5

cGU+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPk5hcmdpLCBKLiBMLjwvYXV0aG9yPjxh

dXRob3I+UmF0YW4sIFIuIFIuPC9hdXRob3I+PGF1dGhvcj5HcmlmZmluLCBELiBFLjwvYXV0aG9y

PjwvYXV0aG9ycz48L2NvbnRyaWJ1dG9ycz48YXV0aC1hZGRyZXNzPkRlcGFydG1lbnQgb2YgTW9s

ZWN1bGFyIE1pY3JvYmlvbG9neSBhbmQgSW1tdW5vbG9neSwgSm9obnMgSG9wa2lucyBVbml2ZXJz

aXR5IFNjaG9vbCBvZiBIeWdpZW5lIGFuZCBQdWJsaWMgSGVhbHRoLCBCYWx0aW1vcmUsIE1EIDIx

MjA1LCBVU0EuPC9hdXRoLWFkZHJlc3M+PHRpdGxlcz48dGl0bGU+cDUzLWluZGVwZW5kZW50IGlu

aGliaXRpb24gb2YgcHJvbGlmZXJhdGlvbiBhbmQgcDIxKFdBRjEvQ2lwMSktbW9kdWxhdGVkIGlu

ZHVjdGlvbiBvZiBjZWxsIGRlYXRoIGJ5IHRoZSBhbnRpb3hpZGFudHMgTi1hY2V0eWxjeXN0ZWlu

ZSBhbmQgdml0YW1pbiBFPC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPk5lb3BsYXNpYTwvc2Vjb25k

YXJ5LXRpdGxlPjxhbHQtdGl0bGU+TmVvcGxhc2lhIChOZXcgWW9yaywgTi5ZLik8L2FsdC10aXRs

ZT48L3RpdGxlcz48cGVyaW9kaWNhbD48ZnVsbC10aXRsZT5OZW9wbGFzaWE8L2Z1bGwtdGl0bGU+

PGFiYnItMT5OZW9wbGFzaWEgKE5ldyBZb3JrLCBOLlkuKTwvYWJici0xPjwvcGVyaW9kaWNhbD48

YWx0LXBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+TmVvcGxhc2lhPC9mdWxsLXRpdGxlPjxhYmJyLTE+

TmVvcGxhc2lhIChOZXcgWW9yaywgTi5ZLik8L2FiYnItMT48L2FsdC1wZXJpb2RpY2FsPjxwYWdl

cz41NDQtNTY8L3BhZ2VzPjx2b2x1bWU+MTwvdm9sdW1lPjxudW1iZXI+NjwvbnVtYmVyPjxlZGl0

aW9uPjIwMDAvMDgvMTA8L2VkaXRpb24+PGtleXdvcmRzPjxrZXl3b3JkPkFjZXR5bGN5c3RlaW5l

LyBwaGFybWFjb2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+QW50aW94aWRhbnRzLyBwaGFybWFjb2xv

Z3k8L2tleXdvcmQ+PGtleXdvcmQ+QXBvcHRvc2lzLyBkcnVnIGVmZmVjdHM8L2tleXdvcmQ+PGtl

eXdvcmQ+Q2VsbCBEaXZpc2lvbi9kcnVnIGVmZmVjdHM8L2tleXdvcmQ+PGtleXdvcmQ+Q2VsbHMs

IEN1bHR1cmVkPC9rZXl3b3JkPjxrZXl3b3JkPkN5Y2xpbi1EZXBlbmRlbnQgS2luYXNlIEluaGli

aXRvciBwMjE8L2tleXdvcmQ+PGtleXdvcmQ+Q3ljbGlucy8gcGh5c2lvbG9neTwva2V5d29yZD48

a2V5d29yZD5IdW1hbnM8L2tleXdvcmQ+PGtleXdvcmQ+UGhvc3Bob3J5bGF0aW9uPC9rZXl3b3Jk

PjxrZXl3b3JkPlJlYWN0aXZlIE94eWdlbiBTcGVjaWVzL21ldGFib2xpc208L2tleXdvcmQ+PGtl

eXdvcmQ+UmV0aW5vYmxhc3RvbWEgUHJvdGVpbi9tZXRhYm9saXNtPC9rZXl3b3JkPjxrZXl3b3Jk

PlR1bW9yIFN1cHByZXNzb3IgUHJvdGVpbiBwNTMvIHBoeXNpb2xvZ3k8L2tleXdvcmQ+PGtleXdv

cmQ+Vml0YW1pbiBFLyBwaGFybWFjb2xvZ3k8L2tleXdvcmQ+PC9rZXl3b3Jkcz48ZGF0ZXM+PHll

YXI+MTk5OTwveWVhcj48cHViLWRhdGVzPjxkYXRlPkRlYzwvZGF0ZT48L3B1Yi1kYXRlcz48L2Rh

dGVzPjxpc2JuPjE1MjItODAwMiAoUHJpbnQpJiN4RDsxNDc2LTU1ODYgKExpbmtpbmcpPC9pc2Ju

PjxhY2Nlc3Npb24tbnVtPjEwOTM1NTAyPC9hY2Nlc3Npb24tbnVtPjx1cmxzPjwvdXJscz48Y3Vz

dG9tMj5QTUMxNTA4MTIzPC9jdXN0b20yPjxyZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+TkxNPC9y

ZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+PGxhbmd1YWdlPmVuZzwvbGFuZ3VhZ2U+PC9yZWNvcmQ+

PC9DaXRlPjxDaXRlPjxBdXRob3I+U2F0bzwvQXV0aG9yPjxZZWFyPjIwMDk8L1llYXI+PFJlY051

bT40NjI8L1JlY051bT48cmVjb3JkPjxyZWMtbnVtYmVyPjQ2MjwvcmVjLW51bWJlcj48Zm9yZWln

bi1rZXlzPjxrZXkgYXBwPSJFTiIgZGItaWQ9Incyd2Z4YWZlNnZhOXo1ZWV2Mmw1NWFhOHN4c2E1

OTllZXYycyI+NDYyPC9rZXk+PC9mb3JlaWduLWtleXM+PHJlZi10eXBlIG5hbWU9IkpvdXJuYWwg

QXJ0aWNsZSI+MTc8L3JlZi10eXBlPjxjb250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5TYXRv

LCBOLjwvYXV0aG9yPjxhdXRob3I+VWVubywgVC48L2F1dGhvcj48YXV0aG9yPkt1Ym8sIEsuPC9h

dXRob3I+PGF1dGhvcj5TdXp1a2ksIFQuPC9hdXRob3I+PGF1dGhvcj5Uc3VraW11cmEsIE4uPC9h

dXRob3I+PGF1dGhvcj5BdHQsIFcuPC9hdXRob3I+PGF1dGhvcj5ZYW1hZGEsIE0uPC9hdXRob3I+

PGF1dGhvcj5Ib3JpLCBOLjwvYXV0aG9yPjxhdXRob3I+TWFlZGEsIEguPC9hdXRob3I+PGF1dGhv

cj5PZ2F3YSwgVC48L2F1dGhvcj48L2F1dGhvcnM+PC9jb250cmlidXRvcnM+PGF1dGgtYWRkcmVz

cz5MYWJvcmF0b3J5IG9mIEJvbmUgYW5kIEltcGxhbnQgU2NpZW5jZXMgKExCSVMpLCBXZWludHJh

dWIgQ2VudGVyIGZvciBSZWNvbnN0cnVjdGl2ZSBCaW90ZWNobm9sb2d5LCBEaXZpc2lvbiBvZiBB

ZHZhbmNlZCBQcm9zdGhvZG9udGljcywgQmlvbWF0ZXJpYWxzIGFuZCBIb3NwaXRhbCBEZW50aXN0

cnksIFVDTEEgU2Nob29sIG9mIERlbnRpc3RyeSwgTG9zIEFuZ2VsZXMsIENBLCBVU0EuPC9hdXRo

LWFkZHJlc3M+PHRpdGxlcz48dGl0bGU+Ti1BY2V0eWwgY3lzdGVpbmUgKE5BQykgaW5oaWJpdHMg

cHJvbGlmZXJhdGlvbiwgY29sbGFnZW4gZ2VuZSB0cmFuc2NyaXB0aW9uLCBhbmQgcmVkb3ggc3Ry

ZXNzIGluIHJhdCBwYWxhdGFsIG11Y29zYWwgY2VsbHM8L3RpdGxlPjxzZWNvbmRhcnktdGl0bGU+

RGVudCBNYXRlcjwvc2Vjb25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+RGVudGFsIG1hdGVyaWFscyA6

IG9mZmljaWFsIHB1YmxpY2F0aW9uIG9mIHRoZSBBY2FkZW15IG9mIERlbnRhbCBNYXRlcmlhbHM8

L2FsdC10aXRsZT48L3RpdGxlcz48cGVyaW9kaWNhbD48ZnVsbC10aXRsZT5EZW50IE1hdGVyPC9m

dWxsLXRpdGxlPjxhYmJyLTE+RGVudGFsIG1hdGVyaWFscyA6IG9mZmljaWFsIHB1YmxpY2F0aW9u

IG9mIHRoZSBBY2FkZW15IG9mIERlbnRhbCBNYXRlcmlhbHM8L2FiYnItMT48L3BlcmlvZGljYWw+

PGFsdC1wZXJpb2RpY2FsPjxmdWxsLXRpdGxlPkRlbnQgTWF0ZXI8L2Z1bGwtdGl0bGU+PGFiYnIt

MT5EZW50YWwgbWF0ZXJpYWxzIDogb2ZmaWNpYWwgcHVibGljYXRpb24gb2YgdGhlIEFjYWRlbXkg

b2YgRGVudGFsIE1hdGVyaWFsczwvYWJici0xPjwvYWx0LXBlcmlvZGljYWw+PHBhZ2VzPjE1MzIt

NDA8L3BhZ2VzPjx2b2x1bWU+MjU8L3ZvbHVtZT48bnVtYmVyPjEyPC9udW1iZXI+PGVkaXRpb24+

MjAwOS8wOC8xNTwvZWRpdGlvbj48a2V5d29yZHM+PGtleXdvcmQ+QWNldHlsY3lzdGVpbmUvYWRt

aW5pc3RyYXRpb24gJmFtcDsgZG9zYWdlLyBwaGFybWFjb2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+

QW5pbWFsczwva2V5d29yZD48a2V5d29yZD5BbnRpb3hpZGFudHMvYWRtaW5pc3RyYXRpb24gJmFt

cDsgZG9zYWdlLyBwaGFybWFjb2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+Q2VsbCBQcm9saWZlcmF0

aW9uL2RydWcgZWZmZWN0czwva2V5d29yZD48a2V5d29yZD5DZWxsIFN1cnZpdmFsL2RydWcgZWZm

ZWN0czwva2V5d29yZD48a2V5d29yZD5DZWxscywgQ3VsdHVyZWQ8L2tleXdvcmQ+PGtleXdvcmQ+

Q29sbGFnZW4vYW5hbHlzaXMvIGFudGFnb25pc3RzICZhbXA7IGluaGliaXRvcnMvZ2VuZXRpY3M8

L2tleXdvcmQ+PGtleXdvcmQ+Q29sbGFnZW4gVHlwZSBJL2FuYWx5c2lzL2FudGFnb25pc3RzICZh

bXA7IGluaGliaXRvcnM8L2tleXdvcmQ+PGtleXdvcmQ+Q29sbGFnZW4gVHlwZSBJSUkvYW5hbHlz

aXMvYW50YWdvbmlzdHMgJmFtcDsgaW5oaWJpdG9yczwva2V5d29yZD48a2V5d29yZD5Eb3NlLVJl

c3BvbnNlIFJlbGF0aW9uc2hpcCwgRHJ1Zzwva2V5d29yZD48a2V5d29yZD5EcnVnIENhcnJpZXJz

PC9rZXl3b3JkPjxrZXl3b3JkPkZyZWUgUmFkaWNhbCBTY2F2ZW5nZXJzL2FkbWluaXN0cmF0aW9u

ICZhbXA7IGRvc2FnZS8gcGhhcm1hY29sb2d5PC9rZXl3b3JkPjxrZXl3b3JkPkdsdXRhdGhpb25l

L2FuYWx5c2lzL2RydWcgZWZmZWN0czwva2V5d29yZD48a2V5d29yZD5IeWRyb2dlbiBQZXJveGlk

ZS9waGFybWFjb2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+TW91dGggTXVjb3NhL2N5dG9sb2d5LyBk

cnVnIGVmZmVjdHM8L2tleXdvcmQ+PGtleXdvcmQ+T3hpZGFudHMvcGhhcm1hY29sb2d5PC9rZXl3

b3JkPjxrZXl3b3JkPk94aWRhdGl2ZSBTdHJlc3MvIGRydWcgZWZmZWN0czwva2V5d29yZD48a2V5

d29yZD5Qcm9jb2xsYWdlbi1Qcm9saW5lIERpb3h5Z2VuYXNlL2FuYWx5c2lzL2FudGFnb25pc3Rz

ICZhbXA7IGluaGliaXRvcnM8L2tleXdvcmQ+PGtleXdvcmQ+UmF0czwva2V5d29yZD48a2V5d29y

ZD5SYXRzLCBTcHJhZ3VlLURhd2xleTwva2V5d29yZD48a2V5d29yZD5UcmFuc2NyaXB0aW9uLCBH

ZW5ldGljLyBkcnVnIGVmZmVjdHM8L2tleXdvcmQ+PC9rZXl3b3Jkcz48ZGF0ZXM+PHllYXI+MjAw

OTwveWVhcj48cHViLWRhdGVzPjxkYXRlPkRlYzwvZGF0ZT48L3B1Yi1kYXRlcz48L2RhdGVzPjxp

c2JuPjE4NzktMDA5NyAoRWxlY3Ryb25pYykmI3hEOzAxMDktNTY0MSAoTGlua2luZyk8L2lzYm4+

PGFjY2Vzc2lvbi1udW0+MTk2NzkzNDM8L2FjY2Vzc2lvbi1udW0+PHVybHM+PC91cmxzPjxlbGVj

dHJvbmljLXJlc291cmNlLW51bT4xMC4xMDE2L2ouZGVudGFsLjIwMDkuMDcuMDA2PC9lbGVjdHJv

bmljLXJlc291cmNlLW51bT48cmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPk5MTTwvcmVtb3RlLWRh

dGFiYXNlLXByb3ZpZGVyPjxsYW5ndWFnZT5lbmc8L2xhbmd1YWdlPjwvcmVjb3JkPjwvQ2l0ZT48

L0VuZE5vdGU+

ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5OYXJnaTwvQXV0aG9yPjxZZWFyPjE5OTk8L1llYXI+PFJl

Y051bT40NjE8L1JlY051bT48RGlzcGxheVRleHQ+WzY0LCA2NV08L0Rpc3BsYXlUZXh0PjxyZWNv

cmQ+PHJlYy1udW1iZXI+NDYxPC9yZWMtbnVtYmVyPjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVO

IiBkYi1pZD0idzJ3ZnhhZmU2dmE5ejVlZXYybDU1YWE4c3hzYTU5OWVldjJzIj40NjE8L2tleT48

L2ZvcmVpZ24ta2V5cz48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5

cGU+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPk5hcmdpLCBKLiBMLjwvYXV0aG9yPjxh

dXRob3I+UmF0YW4sIFIuIFIuPC9hdXRob3I+PGF1dGhvcj5HcmlmZmluLCBELiBFLjwvYXV0aG9y

PjwvYXV0aG9ycz48L2NvbnRyaWJ1dG9ycz48YXV0aC1hZGRyZXNzPkRlcGFydG1lbnQgb2YgTW9s

ZWN1bGFyIE1pY3JvYmlvbG9neSBhbmQgSW1tdW5vbG9neSwgSm9obnMgSG9wa2lucyBVbml2ZXJz

aXR5IFNjaG9vbCBvZiBIeWdpZW5lIGFuZCBQdWJsaWMgSGVhbHRoLCBCYWx0aW1vcmUsIE1EIDIx

MjA1LCBVU0EuPC9hdXRoLWFkZHJlc3M+PHRpdGxlcz48dGl0bGU+cDUzLWluZGVwZW5kZW50IGlu

aGliaXRpb24gb2YgcHJvbGlmZXJhdGlvbiBhbmQgcDIxKFdBRjEvQ2lwMSktbW9kdWxhdGVkIGlu

ZHVjdGlvbiBvZiBjZWxsIGRlYXRoIGJ5IHRoZSBhbnRpb3hpZGFudHMgTi1hY2V0eWxjeXN0ZWlu

ZSBhbmQgdml0YW1pbiBFPC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPk5lb3BsYXNpYTwvc2Vjb25k

YXJ5LXRpdGxlPjxhbHQtdGl0bGU+TmVvcGxhc2lhIChOZXcgWW9yaywgTi5ZLik8L2FsdC10aXRs

ZT48L3RpdGxlcz48cGVyaW9kaWNhbD48ZnVsbC10aXRsZT5OZW9wbGFzaWE8L2Z1bGwtdGl0bGU+

PGFiYnItMT5OZW9wbGFzaWEgKE5ldyBZb3JrLCBOLlkuKTwvYWJici0xPjwvcGVyaW9kaWNhbD48

YWx0LXBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+TmVvcGxhc2lhPC9mdWxsLXRpdGxlPjxhYmJyLTE+

TmVvcGxhc2lhIChOZXcgWW9yaywgTi5ZLik8L2FiYnItMT48L2FsdC1wZXJpb2RpY2FsPjxwYWdl

cz41NDQtNTY8L3BhZ2VzPjx2b2x1bWU+MTwvdm9sdW1lPjxudW1iZXI+NjwvbnVtYmVyPjxlZGl0

aW9uPjIwMDAvMDgvMTA8L2VkaXRpb24+PGtleXdvcmRzPjxrZXl3b3JkPkFjZXR5bGN5c3RlaW5l

LyBwaGFybWFjb2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+QW50aW94aWRhbnRzLyBwaGFybWFjb2xv

Z3k8L2tleXdvcmQ+PGtleXdvcmQ+QXBvcHRvc2lzLyBkcnVnIGVmZmVjdHM8L2tleXdvcmQ+PGtl

eXdvcmQ+Q2VsbCBEaXZpc2lvbi9kcnVnIGVmZmVjdHM8L2tleXdvcmQ+PGtleXdvcmQ+Q2VsbHMs

IEN1bHR1cmVkPC9rZXl3b3JkPjxrZXl3b3JkPkN5Y2xpbi1EZXBlbmRlbnQgS2luYXNlIEluaGli

aXRvciBwMjE8L2tleXdvcmQ+PGtleXdvcmQ+Q3ljbGlucy8gcGh5c2lvbG9neTwva2V5d29yZD48

a2V5d29yZD5IdW1hbnM8L2tleXdvcmQ+PGtleXdvcmQ+UGhvc3Bob3J5bGF0aW9uPC9rZXl3b3Jk

PjxrZXl3b3JkPlJlYWN0aXZlIE94eWdlbiBTcGVjaWVzL21ldGFib2xpc208L2tleXdvcmQ+PGtl

eXdvcmQ+UmV0aW5vYmxhc3RvbWEgUHJvdGVpbi9tZXRhYm9saXNtPC9rZXl3b3JkPjxrZXl3b3Jk

PlR1bW9yIFN1cHByZXNzb3IgUHJvdGVpbiBwNTMvIHBoeXNpb2xvZ3k8L2tleXdvcmQ+PGtleXdv

cmQ+Vml0YW1pbiBFLyBwaGFybWFjb2xvZ3k8L2tleXdvcmQ+PC9rZXl3b3Jkcz48ZGF0ZXM+PHll

YXI+MTk5OTwveWVhcj48cHViLWRhdGVzPjxkYXRlPkRlYzwvZGF0ZT48L3B1Yi1kYXRlcz48L2Rh

dGVzPjxpc2JuPjE1MjItODAwMiAoUHJpbnQpJiN4RDsxNDc2LTU1ODYgKExpbmtpbmcpPC9pc2Ju

PjxhY2Nlc3Npb24tbnVtPjEwOTM1NTAyPC9hY2Nlc3Npb24tbnVtPjx1cmxzPjwvdXJscz48Y3Vz

dG9tMj5QTUMxNTA4MTIzPC9jdXN0b20yPjxyZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+TkxNPC9y

ZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+PGxhbmd1YWdlPmVuZzwvbGFuZ3VhZ2U+PC9yZWNvcmQ+

PC9DaXRlPjxDaXRlPjxBdXRob3I+U2F0bzwvQXV0aG9yPjxZZWFyPjIwMDk8L1llYXI+PFJlY051

bT40NjI8L1JlY051bT48cmVjb3JkPjxyZWMtbnVtYmVyPjQ2MjwvcmVjLW51bWJlcj48Zm9yZWln

bi1rZXlzPjxrZXkgYXBwPSJFTiIgZGItaWQ9Incyd2Z4YWZlNnZhOXo1ZWV2Mmw1NWFhOHN4c2E1

OTllZXYycyI+NDYyPC9rZXk+PC9mb3JlaWduLWtleXM+PHJlZi10eXBlIG5hbWU9IkpvdXJuYWwg

QXJ0aWNsZSI+MTc8L3JlZi10eXBlPjxjb250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5TYXRv

LCBOLjwvYXV0aG9yPjxhdXRob3I+VWVubywgVC48L2F1dGhvcj48YXV0aG9yPkt1Ym8sIEsuPC9h

dXRob3I+PGF1dGhvcj5TdXp1a2ksIFQuPC9hdXRob3I+PGF1dGhvcj5Uc3VraW11cmEsIE4uPC9h

dXRob3I+PGF1dGhvcj5BdHQsIFcuPC9hdXRob3I+PGF1dGhvcj5ZYW1hZGEsIE0uPC9hdXRob3I+

PGF1dGhvcj5Ib3JpLCBOLjwvYXV0aG9yPjxhdXRob3I+TWFlZGEsIEguPC9hdXRob3I+PGF1dGhv

cj5PZ2F3YSwgVC48L2F1dGhvcj48L2F1dGhvcnM+PC9jb250cmlidXRvcnM+PGF1dGgtYWRkcmVz

cz5MYWJvcmF0b3J5IG9mIEJvbmUgYW5kIEltcGxhbnQgU2NpZW5jZXMgKExCSVMpLCBXZWludHJh

dWIgQ2VudGVyIGZvciBSZWNvbnN0cnVjdGl2ZSBCaW90ZWNobm9sb2d5LCBEaXZpc2lvbiBvZiBB

ZHZhbmNlZCBQcm9zdGhvZG9udGljcywgQmlvbWF0ZXJpYWxzIGFuZCBIb3NwaXRhbCBEZW50aXN0

cnksIFVDTEEgU2Nob29sIG9mIERlbnRpc3RyeSwgTG9zIEFuZ2VsZXMsIENBLCBVU0EuPC9hdXRo

LWFkZHJlc3M+PHRpdGxlcz48dGl0bGU+Ti1BY2V0eWwgY3lzdGVpbmUgKE5BQykgaW5oaWJpdHMg

cHJvbGlmZXJhdGlvbiwgY29sbGFnZW4gZ2VuZSB0cmFuc2NyaXB0aW9uLCBhbmQgcmVkb3ggc3Ry

ZXNzIGluIHJhdCBwYWxhdGFsIG11Y29zYWwgY2VsbHM8L3RpdGxlPjxzZWNvbmRhcnktdGl0bGU+

RGVudCBNYXRlcjwvc2Vjb25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+RGVudGFsIG1hdGVyaWFscyA6

IG9mZmljaWFsIHB1YmxpY2F0aW9uIG9mIHRoZSBBY2FkZW15IG9mIERlbnRhbCBNYXRlcmlhbHM8

L2FsdC10aXRsZT48L3RpdGxlcz48cGVyaW9kaWNhbD48ZnVsbC10aXRsZT5EZW50IE1hdGVyPC9m

dWxsLXRpdGxlPjxhYmJyLTE+RGVudGFsIG1hdGVyaWFscyA6IG9mZmljaWFsIHB1YmxpY2F0aW9u

IG9mIHRoZSBBY2FkZW15IG9mIERlbnRhbCBNYXRlcmlhbHM8L2FiYnItMT48L3BlcmlvZGljYWw+

PGFsdC1wZXJpb2RpY2FsPjxmdWxsLXRpdGxlPkRlbnQgTWF0ZXI8L2Z1bGwtdGl0bGU+PGFiYnIt

MT5EZW50YWwgbWF0ZXJpYWxzIDogb2ZmaWNpYWwgcHVibGljYXRpb24gb2YgdGhlIEFjYWRlbXkg

b2YgRGVudGFsIE1hdGVyaWFsczwvYWJici0xPjwvYWx0LXBlcmlvZGljYWw+PHBhZ2VzPjE1MzIt

NDA8L3BhZ2VzPjx2b2x1bWU+MjU8L3ZvbHVtZT48bnVtYmVyPjEyPC9udW1iZXI+PGVkaXRpb24+

MjAwOS8wOC8xNTwvZWRpdGlvbj48a2V5d29yZHM+PGtleXdvcmQ+QWNldHlsY3lzdGVpbmUvYWRt

aW5pc3RyYXRpb24gJmFtcDsgZG9zYWdlLyBwaGFybWFjb2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+

QW5pbWFsczwva2V5d29yZD48a2V5d29yZD5BbnRpb3hpZGFudHMvYWRtaW5pc3RyYXRpb24gJmFt

cDsgZG9zYWdlLyBwaGFybWFjb2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+Q2VsbCBQcm9saWZlcmF0

aW9uL2RydWcgZWZmZWN0czwva2V5d29yZD48a2V5d29yZD5DZWxsIFN1cnZpdmFsL2RydWcgZWZm

ZWN0czwva2V5d29yZD48a2V5d29yZD5DZWxscywgQ3VsdHVyZWQ8L2tleXdvcmQ+PGtleXdvcmQ+

Q29sbGFnZW4vYW5hbHlzaXMvIGFudGFnb25pc3RzICZhbXA7IGluaGliaXRvcnMvZ2VuZXRpY3M8

L2tleXdvcmQ+PGtleXdvcmQ+Q29sbGFnZW4gVHlwZSBJL2FuYWx5c2lzL2FudGFnb25pc3RzICZh

bXA7IGluaGliaXRvcnM8L2tleXdvcmQ+PGtleXdvcmQ+Q29sbGFnZW4gVHlwZSBJSUkvYW5hbHlz

aXMvYW50YWdvbmlzdHMgJmFtcDsgaW5oaWJpdG9yczwva2V5d29yZD48a2V5d29yZD5Eb3NlLVJl

c3BvbnNlIFJlbGF0aW9uc2hpcCwgRHJ1Zzwva2V5d29yZD48a2V5d29yZD5EcnVnIENhcnJpZXJz

PC9rZXl3b3JkPjxrZXl3b3JkPkZyZWUgUmFkaWNhbCBTY2F2ZW5nZXJzL2FkbWluaXN0cmF0aW9u

ICZhbXA7IGRvc2FnZS8gcGhhcm1hY29sb2d5PC9rZXl3b3JkPjxrZXl3b3JkPkdsdXRhdGhpb25l

L2FuYWx5c2lzL2RydWcgZWZmZWN0czwva2V5d29yZD48a2V5d29yZD5IeWRyb2dlbiBQZXJveGlk

ZS9waGFybWFjb2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+TW91dGggTXVjb3NhL2N5dG9sb2d5LyBk

cnVnIGVmZmVjdHM8L2tleXdvcmQ+PGtleXdvcmQ+T3hpZGFudHMvcGhhcm1hY29sb2d5PC9rZXl3

b3JkPjxrZXl3b3JkPk94aWRhdGl2ZSBTdHJlc3MvIGRydWcgZWZmZWN0czwva2V5d29yZD48a2V5

d29yZD5Qcm9jb2xsYWdlbi1Qcm9saW5lIERpb3h5Z2VuYXNlL2FuYWx5c2lzL2FudGFnb25pc3Rz

ICZhbXA7IGluaGliaXRvcnM8L2tleXdvcmQ+PGtleXdvcmQ+UmF0czwva2V5d29yZD48a2V5d29y

ZD5SYXRzLCBTcHJhZ3VlLURhd2xleTwva2V5d29yZD48a2V5d29yZD5UcmFuc2NyaXB0aW9uLCBH

ZW5ldGljLyBkcnVnIGVmZmVjdHM8L2tleXdvcmQ+PC9rZXl3b3Jkcz48ZGF0ZXM+PHllYXI+MjAw

OTwveWVhcj48cHViLWRhdGVzPjxkYXRlPkRlYzwvZGF0ZT48L3B1Yi1kYXRlcz48L2RhdGVzPjxp

c2JuPjE4NzktMDA5NyAoRWxlY3Ryb25pYykmI3hEOzAxMDktNTY0MSAoTGlua2luZyk8L2lzYm4+

PGFjY2Vzc2lvbi1udW0+MTk2NzkzNDM8L2FjY2Vzc2lvbi1udW0+PHVybHM+PC91cmxzPjxlbGVj

dHJvbmljLXJlc291cmNlLW51bT4xMC4xMDE2L2ouZGVudGFsLjIwMDkuMDcuMDA2PC9lbGVjdHJv

bmljLXJlc291cmNlLW51bT48cmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPk5MTTwvcmVtb3RlLWRh

dGFiYXNlLXByb3ZpZGVyPjxsYW5ndWFnZT5lbmc8L2xhbmd1YWdlPjwvcmVjb3JkPjwvQ2l0ZT48

L0VuZE5vdGU+

ADDIN EN.CITE.DATA [64, 65].

Исследование пролиферации эмбриональных мышиных фибробластов с различным уровнем экспрессии MnСОД выявило, что пролиферация клеток содержащих MnСОД (+/+) замедляется по мере увеличения плотности популяции (контактное торможение).

Частичное подавление экспрессии MnСОД приводило к тому, что MnСОД (+/-) клетки были нечувствительны к контактному торможению и продолжали пролиферировать. Рост MnСОД (-/-) фибробластов был существенно замедлен. Усиление экспрессии MnСОД в MnСОД (+/-) клетках приводило к замедлению пролиферации. Ингибирование MnСОД в клетках экспрессирующих MnСОД (+/+), наоборот, приводило к усилению пролиферации. Интересно отметить, что обработка MnСОД (+/-) клеток с помощью Tiron, ловушки для O2-•, приводила к понижению уровня O2-• и замедлению пролиферации, указывая на важную роль O2-• в поддержании пролиферации. Замедление пролиферации также сопровождалось повышением концентрации Н2О2, продукта работы MnСОД ADDIN EN.CITE <EndNote><Cite><Author>Sarsour</Author><Year>2008</Year><RecNum>59</RecNum><DisplayText>[66]</DisplayText><record><rec-number>59</rec-number><foreign-keys><key app="EN" db-id="w2wfxafe6va9z5eev2l55aa8sxsa599eev2s">59</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Sarsour, E. H.</author><author>Venkataraman, S.</author><author>Kalen, A. L.</author><author>Oberley, L. W.</author><author>Goswami, P. C.</author></authors></contributors><auth-address>Free Radical and Radiation Biology Program, Department of Radiation Oncology, University of Iowa, Iowa City, IA 52242, USA.</auth-address><titles><title>Manganese superoxide dismutase activity regulates transitions between quiescent and proliferative growth</title><secondary-title>Aging Cell</secondary-title><alt-title>Aging cell</alt-title></titles><periodical><full-title>Aging Cell</full-title><abbr-1>Aging cell</abbr-1></periodical><alt-periodical><full-title>Aging Cell</full-title><abbr-1>Aging cell</abbr-1></alt-periodical><pages>405-17</pages><volume>7</volume><number>3</number><edition>2008/03/12</edition><keywords><keyword>Cell Proliferation</keyword><keyword>Cells, Cultured</keyword><keyword>Cyclin B/metabolism</keyword><keyword>Cyclin B1</keyword><keyword>Cyclin D1/metabolism</keyword><keyword>Fibroblasts/cytology/metabolism</keyword><keyword>Humans</keyword><keyword>Hydrogen Peroxide/analysis</keyword><keyword>Reactive Oxygen Species/analysis/metabolism</keyword><keyword>Superoxide Dismutase/deficiency/ metabolism</keyword><keyword>Superoxides/analysis/metabolism</keyword></keywords><dates><year>2008</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>1474-9726 (Electronic)&#xD;1474-9718 (Linking)</isbn><accession-num>18331617</accession-num><urls></urls><custom2>PMC2538945</custom2><custom6>Nihms59373</custom6><electronic-resource-num>10.1111/j.1474-9726.2008.00384.x</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[66]. Исследование посттрансляционных модификаций в молекуле MnСОД выявило различия в сайтах метилирования в пролиферирующих и покоящихся клетках. Уровень метилирования MnСОД в активно пролиферирующих клетках был ниже, чем в клетках, пролиферация которых была замедленна PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TYXJzb3VyPC9BdXRob3I+PFllYXI+MjAxMjwvWWVhcj48

UmVjTnVtPjc3PC9SZWNOdW0+PERpc3BsYXlUZXh0PlsyN108L0Rpc3BsYXlUZXh0PjxyZWNvcmQ+

PHJlYy1udW1iZXI+Nzc8L3JlYy1udW1iZXI+PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0iRU4iIGRi

LWlkPSJ3MndmeGFmZTZ2YTl6NWVldjJsNTVhYThzeHNhNTk5ZWV2MnMiPjc3PC9rZXk+PC9mb3Jl

aWduLWtleXM+PHJlZi10eXBlIG5hbWU9IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBlPjxj

b250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5TYXJzb3VyLCBFLiBILjwvYXV0aG9yPjxhdXRo

b3I+S2FsZW4sIEEuIEwuPC9hdXRob3I+PGF1dGhvcj5YaWFvLCBaLjwvYXV0aG9yPjxhdXRob3I+

VmVlbnN0cmEsIFQuIEQuPC9hdXRob3I+PGF1dGhvcj5DaGF1ZGh1cmksIEwuPC9hdXRob3I+PGF1

dGhvcj5WZW5rYXRhcmFtYW4sIFMuPC9hdXRob3I+PGF1dGhvcj5SZWlnYW4sIFAuPC9hdXRob3I+

PGF1dGhvcj5CdWV0dG5lciwgRy4gUi48L2F1dGhvcj48YXV0aG9yPkdvc3dhbWksIFAuIEMuPC9h

dXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjxhdXRoLWFkZHJlc3M+RnJlZSBSYWRpY2Fs

IGFuZCBSYWRpYXRpb24gQmlvbG9neSBEaXZpc2lvbiwgRGVwYXJ0bWVudCBvZiBSYWRpYXRpb24g

T25jb2xvZ3ksIFVuaXZlcnNpdHkgb2YgSW93YSwgSW93YSBDaXR5LCBJQSA1MjI0MiwgVVNBLjwv

YXV0aC1hZGRyZXNzPjx0aXRsZXM+PHRpdGxlPk1hbmdhbmVzZSBzdXBlcm94aWRlIGRpc211dGFz

ZSByZWd1bGF0ZXMgYSBtZXRhYm9saWMgc3dpdGNoIGR1cmluZyB0aGUgbWFtbWFsaWFuIGNlbGwg

Y3ljbGU8L3RpdGxlPjxzZWNvbmRhcnktdGl0bGU+Q2FuY2VyIFJlczwvc2Vjb25kYXJ5LXRpdGxl

PjxhbHQtdGl0bGU+Q2FuY2VyIHJlc2VhcmNoPC9hbHQtdGl0bGU+PC90aXRsZXM+PHBlcmlvZGlj

YWw+PGZ1bGwtdGl0bGU+Q2FuY2VyIFJlczwvZnVsbC10aXRsZT48YWJici0xPkNhbmNlciByZXNl

YXJjaDwvYWJici0xPjwvcGVyaW9kaWNhbD48YWx0LXBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+Q2Fu

Y2VyIFJlczwvZnVsbC10aXRsZT48YWJici0xPkNhbmNlciByZXNlYXJjaDwvYWJici0xPjwvYWx0

LXBlcmlvZGljYWw+PHBhZ2VzPjM4MDctMTY8L3BhZ2VzPjx2b2x1bWU+NzI8L3ZvbHVtZT48bnVt

YmVyPjE1PC9udW1iZXI+PGVkaXRpb24+MjAxMi8wNi8yMDwvZWRpdGlvbj48a2V5d29yZHM+PGtl

eXdvcmQ+QW5pbWFsczwva2V5d29yZD48a2V5d29yZD5DZWxsIEN5Y2xlL2dlbmV0aWNzL3BoeXNp

b2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+Q2VsbCBQcm9saWZlcmF0aW9uPC9rZXl3b3JkPjxrZXl3

b3JkPkNlbGxzLCBDdWx0dXJlZDwva2V5d29yZD48a2V5d29yZD5FbWJyeW8sIE1hbW1hbGlhbjwv

a2V5d29yZD48a2V5d29yZD5FbmVyZ3kgTWV0YWJvbGlzbS9nZW5ldGljcy9waHlzaW9sb2d5PC9r

ZXl3b3JkPjxrZXl3b3JkPkdlbmUgS25vY2tvdXQgVGVjaG5pcXVlczwva2V5d29yZD48a2V5d29y

ZD5HbHVjb3NlL21ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+SHVtYW5zPC9rZXl3b3JkPjxr

ZXl3b3JkPk1hbW1hbHMvZ2VuZXRpY3MvbWV0YWJvbGlzbS9waHlzaW9sb2d5PC9rZXl3b3JkPjxr

ZXl3b3JkPk1ldGFib2xpYyBOZXR3b3JrcyBhbmQgUGF0aHdheXMvcGh5c2lvbG9neTwva2V5d29y

ZD48a2V5d29yZD5NaWNlPC9rZXl3b3JkPjxrZXl3b3JkPk1vZGVscywgTW9sZWN1bGFyPC9rZXl3

b3JkPjxrZXl3b3JkPk94eWdlbi9tZXRhYm9saXNtPC9rZXl3b3JkPjxrZXl3b3JkPlN1cGVyb3hp

ZGUgRGlzbXV0YXNlL2NoZW1pc3RyeS9nZW5ldGljcy9tZXRhYm9saXNtLyBwaHlzaW9sb2d5PC9r

ZXl3b3JkPjxrZXl3b3JkPlRyYW5zZmVjdGlvbjwva2V5d29yZD48L2tleXdvcmRzPjxkYXRlcz48

eWVhcj4yMDEyPC95ZWFyPjxwdWItZGF0ZXM+PGRhdGU+QXVnIDE8L2RhdGU+PC9wdWItZGF0ZXM+

PC9kYXRlcz48aXNibj4xNTM4LTc0NDUgKEVsZWN0cm9uaWMpJiN4RDswMDA4LTU0NzIgKExpbmtp

bmcpPC9pc2JuPjxhY2Nlc3Npb24tbnVtPjIyNzEwNDM1PC9hY2Nlc3Npb24tbnVtPjx1cmxzPjwv

dXJscz48Y3VzdG9tMj5QTUMzNDI5MTMwPC9jdXN0b20yPjxjdXN0b202Pk5paG1zMzkzNzk0PC9j

dXN0b202PjxlbGVjdHJvbmljLXJlc291cmNlLW51bT4xMC4xMTU4LzAwMDgtNTQ3Mi5jYW4tMTEt

MTA2MzwvZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+PHJlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj5O

TE08L3JlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj48bGFuZ3VhZ2U+ZW5nPC9sYW5ndWFnZT48L3Jl

Y29yZD48L0NpdGU+PC9FbmROb3RlPgB=

ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TYXJzb3VyPC9BdXRob3I+PFllYXI+MjAxMjwvWWVhcj48

UmVjTnVtPjc3PC9SZWNOdW0+PERpc3BsYXlUZXh0PlsyN108L0Rpc3BsYXlUZXh0PjxyZWNvcmQ+

PHJlYy1udW1iZXI+Nzc8L3JlYy1udW1iZXI+PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0iRU4iIGRi

LWlkPSJ3MndmeGFmZTZ2YTl6NWVldjJsNTVhYThzeHNhNTk5ZWV2MnMiPjc3PC9rZXk+PC9mb3Jl

aWduLWtleXM+PHJlZi10eXBlIG5hbWU9IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBlPjxj

b250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5TYXJzb3VyLCBFLiBILjwvYXV0aG9yPjxhdXRo

b3I+S2FsZW4sIEEuIEwuPC9hdXRob3I+PGF1dGhvcj5YaWFvLCBaLjwvYXV0aG9yPjxhdXRob3I+

VmVlbnN0cmEsIFQuIEQuPC9hdXRob3I+PGF1dGhvcj5DaGF1ZGh1cmksIEwuPC9hdXRob3I+PGF1

dGhvcj5WZW5rYXRhcmFtYW4sIFMuPC9hdXRob3I+PGF1dGhvcj5SZWlnYW4sIFAuPC9hdXRob3I+

PGF1dGhvcj5CdWV0dG5lciwgRy4gUi48L2F1dGhvcj48YXV0aG9yPkdvc3dhbWksIFAuIEMuPC9h

dXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjxhdXRoLWFkZHJlc3M+RnJlZSBSYWRpY2Fs

IGFuZCBSYWRpYXRpb24gQmlvbG9neSBEaXZpc2lvbiwgRGVwYXJ0bWVudCBvZiBSYWRpYXRpb24g

T25jb2xvZ3ksIFVuaXZlcnNpdHkgb2YgSW93YSwgSW93YSBDaXR5LCBJQSA1MjI0MiwgVVNBLjwv

YXV0aC1hZGRyZXNzPjx0aXRsZXM+PHRpdGxlPk1hbmdhbmVzZSBzdXBlcm94aWRlIGRpc211dGFz

ZSByZWd1bGF0ZXMgYSBtZXRhYm9saWMgc3dpdGNoIGR1cmluZyB0aGUgbWFtbWFsaWFuIGNlbGwg

Y3ljbGU8L3RpdGxlPjxzZWNvbmRhcnktdGl0bGU+Q2FuY2VyIFJlczwvc2Vjb25kYXJ5LXRpdGxl

PjxhbHQtdGl0bGU+Q2FuY2VyIHJlc2VhcmNoPC9hbHQtdGl0bGU+PC90aXRsZXM+PHBlcmlvZGlj

YWw+PGZ1bGwtdGl0bGU+Q2FuY2VyIFJlczwvZnVsbC10aXRsZT48YWJici0xPkNhbmNlciByZXNl

YXJjaDwvYWJici0xPjwvcGVyaW9kaWNhbD48YWx0LXBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+Q2Fu

Y2VyIFJlczwvZnVsbC10aXRsZT48YWJici0xPkNhbmNlciByZXNlYXJjaDwvYWJici0xPjwvYWx0

LXBlcmlvZGljYWw+PHBhZ2VzPjM4MDctMTY8L3BhZ2VzPjx2b2x1bWU+NzI8L3ZvbHVtZT48bnVt

YmVyPjE1PC9udW1iZXI+PGVkaXRpb24+MjAxMi8wNi8yMDwvZWRpdGlvbj48a2V5d29yZHM+PGtl

eXdvcmQ+QW5pbWFsczwva2V5d29yZD48a2V5d29yZD5DZWxsIEN5Y2xlL2dlbmV0aWNzL3BoeXNp

b2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+Q2VsbCBQcm9saWZlcmF0aW9uPC9rZXl3b3JkPjxrZXl3

b3JkPkNlbGxzLCBDdWx0dXJlZDwva2V5d29yZD48a2V5d29yZD5FbWJyeW8sIE1hbW1hbGlhbjwv

a2V5d29yZD48a2V5d29yZD5FbmVyZ3kgTWV0YWJvbGlzbS9nZW5ldGljcy9waHlzaW9sb2d5PC9r

ZXl3b3JkPjxrZXl3b3JkPkdlbmUgS25vY2tvdXQgVGVjaG5pcXVlczwva2V5d29yZD48a2V5d29y

ZD5HbHVjb3NlL21ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+SHVtYW5zPC9rZXl3b3JkPjxr

ZXl3b3JkPk1hbW1hbHMvZ2VuZXRpY3MvbWV0YWJvbGlzbS9waHlzaW9sb2d5PC9rZXl3b3JkPjxr

ZXl3b3JkPk1ldGFib2xpYyBOZXR3b3JrcyBhbmQgUGF0aHdheXMvcGh5c2lvbG9neTwva2V5d29y

ZD48a2V5d29yZD5NaWNlPC9rZXl3b3JkPjxrZXl3b3JkPk1vZGVscywgTW9sZWN1bGFyPC9rZXl3

b3JkPjxrZXl3b3JkPk94eWdlbi9tZXRhYm9saXNtPC9rZXl3b3JkPjxrZXl3b3JkPlN1cGVyb3hp

ZGUgRGlzbXV0YXNlL2NoZW1pc3RyeS9nZW5ldGljcy9tZXRhYm9saXNtLyBwaHlzaW9sb2d5PC9r

ZXl3b3JkPjxrZXl3b3JkPlRyYW5zZmVjdGlvbjwva2V5d29yZD48L2tleXdvcmRzPjxkYXRlcz48

eWVhcj4yMDEyPC95ZWFyPjxwdWItZGF0ZXM+PGRhdGU+QXVnIDE8L2RhdGU+PC9wdWItZGF0ZXM+

PC9kYXRlcz48aXNibj4xNTM4LTc0NDUgKEVsZWN0cm9uaWMpJiN4RDswMDA4LTU0NzIgKExpbmtp

bmcpPC9pc2JuPjxhY2Nlc3Npb24tbnVtPjIyNzEwNDM1PC9hY2Nlc3Npb24tbnVtPjx1cmxzPjwv

dXJscz48Y3VzdG9tMj5QTUMzNDI5MTMwPC9jdXN0b20yPjxjdXN0b202Pk5paG1zMzkzNzk0PC9j

dXN0b202PjxlbGVjdHJvbmljLXJlc291cmNlLW51bT4xMC4xMTU4LzAwMDgtNTQ3Mi5jYW4tMTEt

MTA2MzwvZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+PHJlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj5O

TE08L3JlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj48bGFuZ3VhZ2U+ZW5nPC9sYW5ndWFnZT48L3Jl

Y29yZD48L0NpdGU+PC9FbmROb3RlPgB=

ADDIN EN.CITE.DATA [27].

Опухолевые клетки часто характеризуются смещением редокс в более окисленное состояние, что происходит в результате усиления образования АФК и ослабления работы антиоксидантных ферментов PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DaGl1PC9BdXRob3I+PFllYXI+MjAxMjwvWWVhcj48UmVj

TnVtPjI4NDwvUmVjTnVtPjxEaXNwbGF5VGV4dD5bNjctNzBdPC9EaXNwbGF5VGV4dD48cmVjb3Jk

PjxyZWMtbnVtYmVyPjI4NDwvcmVjLW51bWJlcj48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIg

ZGItaWQ9Incyd2Z4YWZlNnZhOXo1ZWV2Mmw1NWFhOHN4c2E1OTllZXYycyI+Mjg0PC9rZXk+PC9m

b3JlaWduLWtleXM+PHJlZi10eXBlIG5hbWU9IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBl

Pjxjb250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5DaGl1LCBKLjwvYXV0aG9yPjxhdXRob3I+

RGF3ZXMsIEkuIFcuPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjxhdXRoLWFkZHJl

c3M+U2Nob29sIG9mIEJpb3RlY2hub2xvZ3kgYW5kIEJpb21vbGVjdWxhciBTY2llbmNlcywgVW5p

dmVyc2l0eSBvZiBOZXcgU291dGggV2FsZXMsIFN5ZG5leSwgTlNXIDIwNTIsIEF1c3RyYWxpYS48

L2F1dGgtYWRkcmVzcz48dGl0bGVzPjx0aXRsZT5SZWRveCBjb250cm9sIG9mIGNlbGwgcHJvbGlm

ZXJhdGlvbjwvdGl0bGU+PHNlY29uZGFyeS10aXRsZT5UcmVuZHMgQ2VsbCBCaW9sPC9zZWNvbmRh

cnktdGl0bGU+PGFsdC10aXRsZT5UcmVuZHMgaW4gY2VsbCBiaW9sb2d5PC9hbHQtdGl0bGU+PC90

aXRsZXM+PHBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+VHJlbmRzIENlbGwgQmlvbDwvZnVsbC10aXRs

ZT48YWJici0xPlRyZW5kcyBpbiBjZWxsIGJpb2xvZ3k8L2FiYnItMT48L3BlcmlvZGljYWw+PGFs

dC1wZXJpb2RpY2FsPjxmdWxsLXRpdGxlPlRyZW5kcyBDZWxsIEJpb2w8L2Z1bGwtdGl0bGU+PGFi

YnItMT5UcmVuZHMgaW4gY2VsbCBiaW9sb2d5PC9hYmJyLTE+PC9hbHQtcGVyaW9kaWNhbD48cGFn

ZXM+NTkyLTYwMTwvcGFnZXM+PHZvbHVtZT4yMjwvdm9sdW1lPjxudW1iZXI+MTE8L251bWJlcj48

ZWRpdGlvbj4yMDEyLzA5LzA3PC9lZGl0aW9uPjxrZXl3b3Jkcz48a2V5d29yZD5BbmltYWxzPC9r

ZXl3b3JkPjxrZXl3b3JkPkNlbGwgQ3ljbGU8L2tleXdvcmQ+PGtleXdvcmQ+Q2VsbCBQcm9saWZl

cmF0aW9uPC9rZXl3b3JkPjxrZXl3b3JkPkN5dG9raW5lcy9tZXRhYm9saXNtPC9rZXl3b3JkPjxr

ZXl3b3JkPkh1bWFuczwva2V5d29yZD48a2V5d29yZD5PeGlkYXRpb24tUmVkdWN0aW9uPC9rZXl3

b3JkPjxrZXl3b3JkPk94aWRhdGl2ZSBTdHJlc3M8L2tleXdvcmQ+PGtleXdvcmQ+U2lnbmFsIFRy

YW5zZHVjdGlvbjwva2V5d29yZD48L2tleXdvcmRzPjxkYXRlcz48eWVhcj4yMDEyPC95ZWFyPjxw

dWItZGF0ZXM+PGRhdGU+Tm92PC9kYXRlPjwvcHViLWRhdGVzPjwvZGF0ZXM+PGlzYm4+MTg3OS0z

MDg4IChFbGVjdHJvbmljKSYjeEQ7MDk2Mi04OTI0IChMaW5raW5nKTwvaXNibj48YWNjZXNzaW9u

LW51bT4yMjk1MTA3MzwvYWNjZXNzaW9uLW51bT48dXJscz48L3VybHM+PGVsZWN0cm9uaWMtcmVz

b3VyY2UtbnVtPjEwLjEwMTYvai50Y2IuMjAxMi4wOC4wMDI8L2VsZWN0cm9uaWMtcmVzb3VyY2Ut

bnVtPjxyZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+TkxNPC9yZW1vdGUtZGF0YWJhc2UtcHJvdmlk

ZXI+PGxhbmd1YWdlPmVuZzwvbGFuZ3VhZ2U+PC9yZWNvcmQ+PC9DaXRlPjxDaXRlPjxBdXRob3I+

R2l1czwvQXV0aG9yPjxZZWFyPjIwMDY8L1llYXI+PFJlY051bT40MTE8L1JlY051bT48cmVjb3Jk

PjxyZWMtbnVtYmVyPjQxMTwvcmVjLW51bWJlcj48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIg

ZGItaWQ9Incyd2Z4YWZlNnZhOXo1ZWV2Mmw1NWFhOHN4c2E1OTllZXYycyI+NDExPC9rZXk+PC9m

b3JlaWduLWtleXM+PHJlZi10eXBlIG5hbWU9IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBl

Pjxjb250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5HaXVzLCBELjwvYXV0aG9yPjxhdXRob3I+

U3BpdHosIEQuIFIuPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjx0aXRsZXM+PHRp

dGxlPlJlZG94IHNpZ25hbGluZyBpbiBjYW5jZXIgYmlvbG9neTwvdGl0bGU+PHNlY29uZGFyeS10

aXRsZT5BbnRpb3hpZCBSZWRveCBTaWduYWw8L3NlY29uZGFyeS10aXRsZT48YWx0LXRpdGxlPkFu

dGlveGlkYW50cyAmYW1wOyByZWRveCBzaWduYWxpbmc8L2FsdC10aXRsZT48L3RpdGxlcz48cGVy

aW9kaWNhbD48ZnVsbC10aXRsZT5BbnRpb3hpZCBSZWRveCBTaWduYWw8L2Z1bGwtdGl0bGU+PGFi

YnItMT5BbnRpb3hpZGFudHMgJmFtcDsgcmVkb3ggc2lnbmFsaW5nPC9hYmJyLTE+PC9wZXJpb2Rp

Y2FsPjxhbHQtcGVyaW9kaWNhbD48ZnVsbC10aXRsZT5BbnRpb3hpZCBSZWRveCBTaWduYWw8L2Z1

bGwtdGl0bGU+PGFiYnItMT5BbnRpb3hpZGFudHMgJmFtcDsgcmVkb3ggc2lnbmFsaW5nPC9hYmJy

LTE+PC9hbHQtcGVyaW9kaWNhbD48cGFnZXM+MTI0OS01MjwvcGFnZXM+PHZvbHVtZT44PC92b2x1

bWU+PG51bWJlcj43LTg8L251bWJlcj48ZWRpdGlvbj4yMDA2LzA4LzE3PC9lZGl0aW9uPjxrZXl3

b3Jkcz48a2V5d29yZD5BbmltYWxzPC9rZXl3b3JkPjxrZXl3b3JkPkZyZWUgUmFkaWNhbHMvbWV0

YWJvbGlzbTwva2V5d29yZD48a2V5d29yZD5IdW1hbnM8L2tleXdvcmQ+PGtleXdvcmQ+TmVvcGxh

c21zL2V0aW9sb2d5LyBtZXRhYm9saXNtLyBwYXRob2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+Tml0

cmljIE94aWRlL21ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+T3hpZGF0aW9uLVJlZHVjdGlv

bi9kcnVnIGVmZmVjdHMvcmFkaWF0aW9uIGVmZmVjdHM8L2tleXdvcmQ+PGtleXdvcmQ+UmFkaWF0

aW9uLCBJb25pemluZzwva2V5d29yZD48a2V5d29yZD5SZWFjdGl2ZSBOaXRyb2dlbiBTcGVjaWVz

L21ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+UmVhY3RpdmUgT3h5Z2VuIFNwZWNpZXMvbWV0

YWJvbGlzbTwva2V5d29yZD48a2V5d29yZD5TaWduYWwgVHJhbnNkdWN0aW9uPC9rZXl3b3JkPjxr

ZXl3b3JkPlhlbm9iaW90aWNzL3BoYXJtYWNvbG9neTwva2V5d29yZD48L2tleXdvcmRzPjxkYXRl

cz48eWVhcj4yMDA2PC95ZWFyPjxwdWItZGF0ZXM+PGRhdGU+SnVsLUF1ZzwvZGF0ZT48L3B1Yi1k

YXRlcz48L2RhdGVzPjxpc2JuPjE1MjMtMDg2NCAoUHJpbnQpJiN4RDsxNTIzLTA4NjQgKExpbmtp

bmcpPC9pc2JuPjxhY2Nlc3Npb24tbnVtPjE2OTEwNzcyPC9hY2Nlc3Npb24tbnVtPjx1cmxzPjwv

dXJscz48ZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+MTAuMTA4OS9hcnMuMjAwNi44LjEyNDk8L2Vs

ZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjxyZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+TkxNPC9yZW1v

dGUtZGF0YWJhc2UtcHJvdmlkZXI+PGxhbmd1YWdlPmVuZzwvbGFuZ3VhZ2U+PC9yZWNvcmQ+PC9D

aXRlPjxDaXRlPjxBdXRob3I+R3VwdGE8L0F1dGhvcj48WWVhcj4yMDEyPC9ZZWFyPjxSZWNOdW0+

Mjk5PC9SZWNOdW0+PHJlY29yZD48cmVjLW51bWJlcj4yOTk8L3JlYy1udW1iZXI+PGZvcmVpZ24t

a2V5cz48a2V5IGFwcD0iRU4iIGRiLWlkPSJ3MndmeGFmZTZ2YTl6NWVldjJsNTVhYThzeHNhNTk5

ZWV2MnMiPjI5OTwva2V5PjwvZm9yZWlnbi1rZXlzPjxyZWYtdHlwZSBuYW1lPSJKb3VybmFsIEFy

dGljbGUiPjE3PC9yZWYtdHlwZT48Y29udHJpYnV0b3JzPjxhdXRob3JzPjxhdXRob3I+R3VwdGEs

IFMuIEMuPC9hdXRob3I+PGF1dGhvcj5IZXZpYSwgRC48L2F1dGhvcj48YXV0aG9yPlBhdGNodmEs

IFMuPC9hdXRob3I+PGF1dGhvcj5QYXJrLCBCLjwvYXV0aG9yPjxhdXRob3I+S29oLCBXLjwvYXV0

aG9yPjxhdXRob3I+QWdnYXJ3YWwsIEIuIEIuPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0

b3JzPjxhdXRoLWFkZHJlc3M+Q3l0b2tpbmUgUmVzZWFyY2ggTGFib3JhdG9yeSwgRGVwYXJ0bWVu

dCBvZiBFeHBlcmltZW50YWwgVGhlcmFwZXV0aWNzLCBUaGUgVW5pdmVyc2l0eSBvZiBUZXhhcyBN

RCBBbmRlcnNvbiBDYW5jZXIgQ2VudGVyLCBIb3VzdG9uLCBUZXhhcywgVVNBLjwvYXV0aC1hZGRy

ZXNzPjx0aXRsZXM+PHRpdGxlPlVwc2lkZXMgYW5kIGRvd25zaWRlcyBvZiByZWFjdGl2ZSBveHln

ZW4gc3BlY2llcyBmb3IgY2FuY2VyOiB0aGUgcm9sZXMgb2YgcmVhY3RpdmUgb3h5Z2VuIHNwZWNp

ZXMgaW4gdHVtb3JpZ2VuZXNpcywgcHJldmVudGlvbiwgYW5kIHRoZXJhcHk8L3RpdGxlPjxzZWNv

bmRhcnktdGl0bGU+QW50aW94aWQgUmVkb3ggU2lnbmFsPC9zZWNvbmRhcnktdGl0bGU+PGFsdC10

aXRsZT5BbnRpb3hpZGFudHMgJmFtcDsgcmVkb3ggc2lnbmFsaW5nPC9hbHQtdGl0bGU+PC90aXRs

ZXM+PHBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+QW50aW94aWQgUmVkb3ggU2lnbmFsPC9mdWxsLXRp

dGxlPjxhYmJyLTE+QW50aW94aWRhbnRzICZhbXA7IHJlZG94IHNpZ25hbGluZzwvYWJici0xPjwv

cGVyaW9kaWNhbD48YWx0LXBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+QW50aW94aWQgUmVkb3ggU2ln

bmFsPC9mdWxsLXRpdGxlPjxhYmJyLTE+QW50aW94aWRhbnRzICZhbXA7IHJlZG94IHNpZ25hbGlu

ZzwvYWJici0xPjwvYWx0LXBlcmlvZGljYWw+PHBhZ2VzPjEyOTUtMzIyPC9wYWdlcz48dm9sdW1l

PjE2PC92b2x1bWU+PG51bWJlcj4xMTwvbnVtYmVyPjxlZGl0aW9uPjIwMTEvMTEvMjY8L2VkaXRp

b24+PGtleXdvcmRzPjxrZXl3b3JkPkNlbGwgVHJhbnNmb3JtYXRpb24sIE5lb3BsYXN0aWM8L2tl

eXdvcmQ+PGtleXdvcmQ+Q2xpbmljYWwgVHJpYWxzIGFzIFRvcGljPC9rZXl3b3JkPjxrZXl3b3Jk

PkRydWcgUmVzaXN0YW5jZSwgTmVvcGxhc208L2tleXdvcmQ+PGtleXdvcmQ+SHVtYW5zPC9rZXl3

b3JkPjxrZXl3b3JkPk5lb3BsYXNtcy8gbWV0YWJvbGlzbS9wcmV2ZW50aW9uICZhbXA7IGNvbnRy

b2wvdGhlcmFweTwva2V5d29yZD48a2V5d29yZD5SYWRpYXRpb24gVG9sZXJhbmNlPC9rZXl3b3Jk

PjxrZXl3b3JkPlJlYWN0aXZlIE94eWdlbiBTcGVjaWVzLyBtZXRhYm9saXNtPC9rZXl3b3JkPjwv

a2V5d29yZHM+PGRhdGVzPjx5ZWFyPjIwMTI8L3llYXI+PHB1Yi1kYXRlcz48ZGF0ZT5KdW4gMTwv

ZGF0ZT48L3B1Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjE1NTctNzcxNiAoRWxlY3Ryb25pYykmI3hE

OzE1MjMtMDg2NCAoTGlua2luZyk8L2lzYm4+PGFjY2Vzc2lvbi1udW0+MjIxMTcxMzc8L2FjY2Vz

c2lvbi1udW0+PHVybHM+PC91cmxzPjxjdXN0b20yPlBNQzMzMjQ4MTU8L2N1c3RvbTI+PGVsZWN0

cm9uaWMtcmVzb3VyY2UtbnVtPjEwLjEwODkvYXJzLjIwMTEuNDQxNDwvZWxlY3Ryb25pYy1yZXNv

dXJjZS1udW0+PHJlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj5OTE08L3JlbW90ZS1kYXRhYmFzZS1w

cm92aWRlcj48bGFuZ3VhZ2U+ZW5nPC9sYW5ndWFnZT48L3JlY29yZD48L0NpdGU+PENpdGU+PEF1

dGhvcj5DYWlybnM8L0F1dGhvcj48WWVhcj4yMDExPC9ZZWFyPjxSZWNOdW0+NDQ1PC9SZWNOdW0+

PHJlY29yZD48cmVjLW51bWJlcj40NDU8L3JlYy1udW1iZXI+PGZvcmVpZ24ta2V5cz48a2V5IGFw

cD0iRU4iIGRiLWlkPSJ3MndmeGFmZTZ2YTl6NWVldjJsNTVhYThzeHNhNTk5ZWV2MnMiPjQ0NTwv

a2V5PjwvZm9yZWlnbi1rZXlzPjxyZWYtdHlwZSBuYW1lPSJKb3VybmFsIEFydGljbGUiPjE3PC9y

ZWYtdHlwZT48Y29udHJpYnV0b3JzPjxhdXRob3JzPjxhdXRob3I+Q2Fpcm5zLCBSLiBBLjwvYXV0

aG9yPjxhdXRob3I+SGFycmlzLCBJLiBTLjwvYXV0aG9yPjxhdXRob3I+TWFrLCBULiBXLjwvYXV0

aG9yPjwvYXV0aG9ycz48L2NvbnRyaWJ1dG9ycz48YXV0aC1hZGRyZXNzPlRoZSBDYW1wYmVsbCBG

YW1pbHkgQ2FuY2VyIFJlc2VhcmNoIEluc3RpdHV0ZSwgVG9yb250bywgT04gTTU2IDJNOSwgQ2Fu

YWRhLjwvYXV0aC1hZGRyZXNzPjx0aXRsZXM+PHRpdGxlPlJlZ3VsYXRpb24gb2YgY2FuY2VyIGNl

bGwgbWV0YWJvbGlzbTwvdGl0bGU+PHNlY29uZGFyeS10aXRsZT5OYXQgUmV2IENhbmNlcjwvc2Vj

b25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+TmF0dXJlIHJldmlld3MuIENhbmNlcjwvYWx0LXRpdGxl

PjwvdGl0bGVzPjxwZXJpb2RpY2FsPjxmdWxsLXRpdGxlPk5hdCBSZXYgQ2FuY2VyPC9mdWxsLXRp

dGxlPjxhYmJyLTE+TmF0dXJlIHJldmlld3MuIENhbmNlcjwvYWJici0xPjwvcGVyaW9kaWNhbD48

YWx0LXBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+TmF0IFJldiBDYW5jZXI8L2Z1bGwtdGl0bGU+PGFi

YnItMT5OYXR1cmUgcmV2aWV3cy4gQ2FuY2VyPC9hYmJyLTE+PC9hbHQtcGVyaW9kaWNhbD48cGFn

ZXM+ODUtOTU8L3BhZ2VzPjx2b2x1bWU+MTE8L3ZvbHVtZT48bnVtYmVyPjI8L251bWJlcj48ZWRp

dGlvbj4yMDExLzAxLzI1PC9lZGl0aW9uPjxrZXl3b3Jkcz48a2V5d29yZD5DZWxsIFRyYW5zZm9y

bWF0aW9uLCBOZW9wbGFzdGljL2dlbmV0aWNzLyBtZXRhYm9saXNtPC9rZXl3b3JkPjxrZXl3b3Jk

PkdlbmUgRXhwcmVzc2lvbiBSZWd1bGF0aW9uLCBOZW9wbGFzdGljPC9rZXl3b3JkPjxrZXl3b3Jk

PkdlbmUgUmVndWxhdG9yeSBOZXR3b3Jrczwva2V5d29yZD48a2V5d29yZD5IdW1hbnM8L2tleXdv

cmQ+PGtleXdvcmQ+SW50cmFjZWxsdWxhciBTaWduYWxpbmcgUGVwdGlkZXMgYW5kIFByb3RlaW5z

L21ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+TmVvcGxhc21zL2dlbmV0aWNzLyBtZXRhYm9s

aXNtPC9rZXl3b3JkPjxrZXl3b3JkPk94aWRhdGlvbi1SZWR1Y3Rpb248L2tleXdvcmQ+PGtleXdv

cmQ+U2lnbmFsIFRyYW5zZHVjdGlvbjwva2V5d29yZD48a2V5d29yZD5UcmFuc2NyaXB0aW9uIEZh

Y3RvcnMvbWV0YWJvbGlzbTwva2V5d29yZD48L2tleXdvcmRzPjxkYXRlcz48eWVhcj4yMDExPC95

ZWFyPjxwdWItZGF0ZXM+PGRhdGU+RmViPC9kYXRlPjwvcHViLWRhdGVzPjwvZGF0ZXM+PGlzYm4+

MTQ3NC0xNzY4IChFbGVjdHJvbmljKSYjeEQ7MTQ3NC0xNzVYIChMaW5raW5nKTwvaXNibj48YWNj

ZXNzaW9uLW51bT4yMTI1ODM5NDwvYWNjZXNzaW9uLW51bT48dXJscz48L3VybHM+PGVsZWN0cm9u

aWMtcmVzb3VyY2UtbnVtPjEwLjEwMzgvbnJjMjk4MTwvZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+

PHJlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj5OTE08L3JlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj48

bGFuZ3VhZ2U+ZW5nPC9sYW5ndWFnZT48L3JlY29yZD48L0NpdGU+PC9FbmROb3RlPgB=

ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DaGl1PC9BdXRob3I+PFllYXI+MjAxMjwvWWVhcj48UmVj

TnVtPjI4NDwvUmVjTnVtPjxEaXNwbGF5VGV4dD5bNjctNzBdPC9EaXNwbGF5VGV4dD48cmVjb3Jk

PjxyZWMtbnVtYmVyPjI4NDwvcmVjLW51bWJlcj48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIg

ZGItaWQ9Incyd2Z4YWZlNnZhOXo1ZWV2Mmw1NWFhOHN4c2E1OTllZXYycyI+Mjg0PC9rZXk+PC9m

b3JlaWduLWtleXM+PHJlZi10eXBlIG5hbWU9IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBl

Pjxjb250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5DaGl1LCBKLjwvYXV0aG9yPjxhdXRob3I+

RGF3ZXMsIEkuIFcuPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjxhdXRoLWFkZHJl

c3M+U2Nob29sIG9mIEJpb3RlY2hub2xvZ3kgYW5kIEJpb21vbGVjdWxhciBTY2llbmNlcywgVW5p

dmVyc2l0eSBvZiBOZXcgU291dGggV2FsZXMsIFN5ZG5leSwgTlNXIDIwNTIsIEF1c3RyYWxpYS48

L2F1dGgtYWRkcmVzcz48dGl0bGVzPjx0aXRsZT5SZWRveCBjb250cm9sIG9mIGNlbGwgcHJvbGlm

ZXJhdGlvbjwvdGl0bGU+PHNlY29uZGFyeS10aXRsZT5UcmVuZHMgQ2VsbCBCaW9sPC9zZWNvbmRh

cnktdGl0bGU+PGFsdC10aXRsZT5UcmVuZHMgaW4gY2VsbCBiaW9sb2d5PC9hbHQtdGl0bGU+PC90

aXRsZXM+PHBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+VHJlbmRzIENlbGwgQmlvbDwvZnVsbC10aXRs

ZT48YWJici0xPlRyZW5kcyBpbiBjZWxsIGJpb2xvZ3k8L2FiYnItMT48L3BlcmlvZGljYWw+PGFs

dC1wZXJpb2RpY2FsPjxmdWxsLXRpdGxlPlRyZW5kcyBDZWxsIEJpb2w8L2Z1bGwtdGl0bGU+PGFi

YnItMT5UcmVuZHMgaW4gY2VsbCBiaW9sb2d5PC9hYmJyLTE+PC9hbHQtcGVyaW9kaWNhbD48cGFn

ZXM+NTkyLTYwMTwvcGFnZXM+PHZvbHVtZT4yMjwvdm9sdW1lPjxudW1iZXI+MTE8L251bWJlcj48

ZWRpdGlvbj4yMDEyLzA5LzA3PC9lZGl0aW9uPjxrZXl3b3Jkcz48a2V5d29yZD5BbmltYWxzPC9r

ZXl3b3JkPjxrZXl3b3JkPkNlbGwgQ3ljbGU8L2tleXdvcmQ+PGtleXdvcmQ+Q2VsbCBQcm9saWZl

cmF0aW9uPC9rZXl3b3JkPjxrZXl3b3JkPkN5dG9raW5lcy9tZXRhYm9saXNtPC9rZXl3b3JkPjxr

ZXl3b3JkPkh1bWFuczwva2V5d29yZD48a2V5d29yZD5PeGlkYXRpb24tUmVkdWN0aW9uPC9rZXl3

b3JkPjxrZXl3b3JkPk94aWRhdGl2ZSBTdHJlc3M8L2tleXdvcmQ+PGtleXdvcmQ+U2lnbmFsIFRy

YW5zZHVjdGlvbjwva2V5d29yZD48L2tleXdvcmRzPjxkYXRlcz48eWVhcj4yMDEyPC95ZWFyPjxw

dWItZGF0ZXM+PGRhdGU+Tm92PC9kYXRlPjwvcHViLWRhdGVzPjwvZGF0ZXM+PGlzYm4+MTg3OS0z

MDg4IChFbGVjdHJvbmljKSYjeEQ7MDk2Mi04OTI0IChMaW5raW5nKTwvaXNibj48YWNjZXNzaW9u

LW51bT4yMjk1MTA3MzwvYWNjZXNzaW9uLW51bT48dXJscz48L3VybHM+PGVsZWN0cm9uaWMtcmVz

b3VyY2UtbnVtPjEwLjEwMTYvai50Y2IuMjAxMi4wOC4wMDI8L2VsZWN0cm9uaWMtcmVzb3VyY2Ut

bnVtPjxyZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+TkxNPC9yZW1vdGUtZGF0YWJhc2UtcHJvdmlk

ZXI+PGxhbmd1YWdlPmVuZzwvbGFuZ3VhZ2U+PC9yZWNvcmQ+PC9DaXRlPjxDaXRlPjxBdXRob3I+

R2l1czwvQXV0aG9yPjxZZWFyPjIwMDY8L1llYXI+PFJlY051bT40MTE8L1JlY051bT48cmVjb3Jk

PjxyZWMtbnVtYmVyPjQxMTwvcmVjLW51bWJlcj48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIg

ZGItaWQ9Incyd2Z4YWZlNnZhOXo1ZWV2Mmw1NWFhOHN4c2E1OTllZXYycyI+NDExPC9rZXk+PC9m

b3JlaWduLWtleXM+PHJlZi10eXBlIG5hbWU9IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBl

Pjxjb250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5HaXVzLCBELjwvYXV0aG9yPjxhdXRob3I+

U3BpdHosIEQuIFIuPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjx0aXRsZXM+PHRp

dGxlPlJlZG94IHNpZ25hbGluZyBpbiBjYW5jZXIgYmlvbG9neTwvdGl0bGU+PHNlY29uZGFyeS10

aXRsZT5BbnRpb3hpZCBSZWRveCBTaWduYWw8L3NlY29uZGFyeS10aXRsZT48YWx0LXRpdGxlPkFu

dGlveGlkYW50cyAmYW1wOyByZWRveCBzaWduYWxpbmc8L2FsdC10aXRsZT48L3RpdGxlcz48cGVy

aW9kaWNhbD48ZnVsbC10aXRsZT5BbnRpb3hpZCBSZWRveCBTaWduYWw8L2Z1bGwtdGl0bGU+PGFi

YnItMT5BbnRpb3hpZGFudHMgJmFtcDsgcmVkb3ggc2lnbmFsaW5nPC9hYmJyLTE+PC9wZXJpb2Rp

Y2FsPjxhbHQtcGVyaW9kaWNhbD48ZnVsbC10aXRsZT5BbnRpb3hpZCBSZWRveCBTaWduYWw8L2Z1

bGwtdGl0bGU+PGFiYnItMT5BbnRpb3hpZGFudHMgJmFtcDsgcmVkb3ggc2lnbmFsaW5nPC9hYmJy

LTE+PC9hbHQtcGVyaW9kaWNhbD48cGFnZXM+MTI0OS01MjwvcGFnZXM+PHZvbHVtZT44PC92b2x1

bWU+PG51bWJlcj43LTg8L251bWJlcj48ZWRpdGlvbj4yMDA2LzA4LzE3PC9lZGl0aW9uPjxrZXl3

b3Jkcz48a2V5d29yZD5BbmltYWxzPC9rZXl3b3JkPjxrZXl3b3JkPkZyZWUgUmFkaWNhbHMvbWV0

YWJvbGlzbTwva2V5d29yZD48a2V5d29yZD5IdW1hbnM8L2tleXdvcmQ+PGtleXdvcmQ+TmVvcGxh

c21zL2V0aW9sb2d5LyBtZXRhYm9saXNtLyBwYXRob2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+Tml0

cmljIE94aWRlL21ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+T3hpZGF0aW9uLVJlZHVjdGlv

bi9kcnVnIGVmZmVjdHMvcmFkaWF0aW9uIGVmZmVjdHM8L2tleXdvcmQ+PGtleXdvcmQ+UmFkaWF0

aW9uLCBJb25pemluZzwva2V5d29yZD48a2V5d29yZD5SZWFjdGl2ZSBOaXRyb2dlbiBTcGVjaWVz

L21ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+UmVhY3RpdmUgT3h5Z2VuIFNwZWNpZXMvbWV0

YWJvbGlzbTwva2V5d29yZD48a2V5d29yZD5TaWduYWwgVHJhbnNkdWN0aW9uPC9rZXl3b3JkPjxr

ZXl3b3JkPlhlbm9iaW90aWNzL3BoYXJtYWNvbG9neTwva2V5d29yZD48L2tleXdvcmRzPjxkYXRl

cz48eWVhcj4yMDA2PC95ZWFyPjxwdWItZGF0ZXM+PGRhdGU+SnVsLUF1ZzwvZGF0ZT48L3B1Yi1k

YXRlcz48L2RhdGVzPjxpc2JuPjE1MjMtMDg2NCAoUHJpbnQpJiN4RDsxNTIzLTA4NjQgKExpbmtp

bmcpPC9pc2JuPjxhY2Nlc3Npb24tbnVtPjE2OTEwNzcyPC9hY2Nlc3Npb24tbnVtPjx1cmxzPjwv

dXJscz48ZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+MTAuMTA4OS9hcnMuMjAwNi44LjEyNDk8L2Vs

ZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjxyZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+TkxNPC9yZW1v

dGUtZGF0YWJhc2UtcHJvdmlkZXI+PGxhbmd1YWdlPmVuZzwvbGFuZ3VhZ2U+PC9yZWNvcmQ+PC9D

aXRlPjxDaXRlPjxBdXRob3I+R3VwdGE8L0F1dGhvcj48WWVhcj4yMDEyPC9ZZWFyPjxSZWNOdW0+

Mjk5PC9SZWNOdW0+PHJlY29yZD48cmVjLW51bWJlcj4yOTk8L3JlYy1udW1iZXI+PGZvcmVpZ24t

a2V5cz48a2V5IGFwcD0iRU4iIGRiLWlkPSJ3MndmeGFmZTZ2YTl6NWVldjJsNTVhYThzeHNhNTk5

ZWV2MnMiPjI5OTwva2V5PjwvZm9yZWlnbi1rZXlzPjxyZWYtdHlwZSBuYW1lPSJKb3VybmFsIEFy

dGljbGUiPjE3PC9yZWYtdHlwZT48Y29udHJpYnV0b3JzPjxhdXRob3JzPjxhdXRob3I+R3VwdGEs

IFMuIEMuPC9hdXRob3I+PGF1dGhvcj5IZXZpYSwgRC48L2F1dGhvcj48YXV0aG9yPlBhdGNodmEs

IFMuPC9hdXRob3I+PGF1dGhvcj5QYXJrLCBCLjwvYXV0aG9yPjxhdXRob3I+S29oLCBXLjwvYXV0

aG9yPjxhdXRob3I+QWdnYXJ3YWwsIEIuIEIuPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0

b3JzPjxhdXRoLWFkZHJlc3M+Q3l0b2tpbmUgUmVzZWFyY2ggTGFib3JhdG9yeSwgRGVwYXJ0bWVu

dCBvZiBFeHBlcmltZW50YWwgVGhlcmFwZXV0aWNzLCBUaGUgVW5pdmVyc2l0eSBvZiBUZXhhcyBN

RCBBbmRlcnNvbiBDYW5jZXIgQ2VudGVyLCBIb3VzdG9uLCBUZXhhcywgVVNBLjwvYXV0aC1hZGRy

ZXNzPjx0aXRsZXM+PHRpdGxlPlVwc2lkZXMgYW5kIGRvd25zaWRlcyBvZiByZWFjdGl2ZSBveHln

ZW4gc3BlY2llcyBmb3IgY2FuY2VyOiB0aGUgcm9sZXMgb2YgcmVhY3RpdmUgb3h5Z2VuIHNwZWNp

ZXMgaW4gdHVtb3JpZ2VuZXNpcywgcHJldmVudGlvbiwgYW5kIHRoZXJhcHk8L3RpdGxlPjxzZWNv

bmRhcnktdGl0bGU+QW50aW94aWQgUmVkb3ggU2lnbmFsPC9zZWNvbmRhcnktdGl0bGU+PGFsdC10

aXRsZT5BbnRpb3hpZGFudHMgJmFtcDsgcmVkb3ggc2lnbmFsaW5nPC9hbHQtdGl0bGU+PC90aXRs

ZXM+PHBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+QW50aW94aWQgUmVkb3ggU2lnbmFsPC9mdWxsLXRp

dGxlPjxhYmJyLTE+QW50aW94aWRhbnRzICZhbXA7IHJlZG94IHNpZ25hbGluZzwvYWJici0xPjwv

cGVyaW9kaWNhbD48YWx0LXBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+QW50aW94aWQgUmVkb3ggU2ln

bmFsPC9mdWxsLXRpdGxlPjxhYmJyLTE+QW50aW94aWRhbnRzICZhbXA7IHJlZG94IHNpZ25hbGlu

ZzwvYWJici0xPjwvYWx0LXBlcmlvZGljYWw+PHBhZ2VzPjEyOTUtMzIyPC9wYWdlcz48dm9sdW1l

PjE2PC92b2x1bWU+PG51bWJlcj4xMTwvbnVtYmVyPjxlZGl0aW9uPjIwMTEvMTEvMjY8L2VkaXRp

b24+PGtleXdvcmRzPjxrZXl3b3JkPkNlbGwgVHJhbnNmb3JtYXRpb24sIE5lb3BsYXN0aWM8L2tl

eXdvcmQ+PGtleXdvcmQ+Q2xpbmljYWwgVHJpYWxzIGFzIFRvcGljPC9rZXl3b3JkPjxrZXl3b3Jk

PkRydWcgUmVzaXN0YW5jZSwgTmVvcGxhc208L2tleXdvcmQ+PGtleXdvcmQ+SHVtYW5zPC9rZXl3

b3JkPjxrZXl3b3JkPk5lb3BsYXNtcy8gbWV0YWJvbGlzbS9wcmV2ZW50aW9uICZhbXA7IGNvbnRy

b2wvdGhlcmFweTwva2V5d29yZD48a2V5d29yZD5SYWRpYXRpb24gVG9sZXJhbmNlPC9rZXl3b3Jk

PjxrZXl3b3JkPlJlYWN0aXZlIE94eWdlbiBTcGVjaWVzLyBtZXRhYm9saXNtPC9rZXl3b3JkPjwv

a2V5d29yZHM+PGRhdGVzPjx5ZWFyPjIwMTI8L3llYXI+PHB1Yi1kYXRlcz48ZGF0ZT5KdW4gMTwv

ZGF0ZT48L3B1Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjE1NTctNzcxNiAoRWxlY3Ryb25pYykmI3hE

OzE1MjMtMDg2NCAoTGlua2luZyk8L2lzYm4+PGFjY2Vzc2lvbi1udW0+MjIxMTcxMzc8L2FjY2Vz

c2lvbi1udW0+PHVybHM+PC91cmxzPjxjdXN0b20yPlBNQzMzMjQ4MTU8L2N1c3RvbTI+PGVsZWN0

cm9uaWMtcmVzb3VyY2UtbnVtPjEwLjEwODkvYXJzLjIwMTEuNDQxNDwvZWxlY3Ryb25pYy1yZXNv

dXJjZS1udW0+PHJlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj5OTE08L3JlbW90ZS1kYXRhYmFzZS1w

cm92aWRlcj48bGFuZ3VhZ2U+ZW5nPC9sYW5ndWFnZT48L3JlY29yZD48L0NpdGU+PENpdGU+PEF1

dGhvcj5DYWlybnM8L0F1dGhvcj48WWVhcj4yMDExPC9ZZWFyPjxSZWNOdW0+NDQ1PC9SZWNOdW0+

PHJlY29yZD48cmVjLW51bWJlcj40NDU8L3JlYy1udW1iZXI+PGZvcmVpZ24ta2V5cz48a2V5IGFw

cD0iRU4iIGRiLWlkPSJ3MndmeGFmZTZ2YTl6NWVldjJsNTVhYThzeHNhNTk5ZWV2MnMiPjQ0NTwv

a2V5PjwvZm9yZWlnbi1rZXlzPjxyZWYtdHlwZSBuYW1lPSJKb3VybmFsIEFydGljbGUiPjE3PC9y

ZWYtdHlwZT48Y29udHJpYnV0b3JzPjxhdXRob3JzPjxhdXRob3I+Q2Fpcm5zLCBSLiBBLjwvYXV0

aG9yPjxhdXRob3I+SGFycmlzLCBJLiBTLjwvYXV0aG9yPjxhdXRob3I+TWFrLCBULiBXLjwvYXV0

aG9yPjwvYXV0aG9ycz48L2NvbnRyaWJ1dG9ycz48YXV0aC1hZGRyZXNzPlRoZSBDYW1wYmVsbCBG

YW1pbHkgQ2FuY2VyIFJlc2VhcmNoIEluc3RpdHV0ZSwgVG9yb250bywgT04gTTU2IDJNOSwgQ2Fu

YWRhLjwvYXV0aC1hZGRyZXNzPjx0aXRsZXM+PHRpdGxlPlJlZ3VsYXRpb24gb2YgY2FuY2VyIGNl

bGwgbWV0YWJvbGlzbTwvdGl0bGU+PHNlY29uZGFyeS10aXRsZT5OYXQgUmV2IENhbmNlcjwvc2Vj

b25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+TmF0dXJlIHJldmlld3MuIENhbmNlcjwvYWx0LXRpdGxl

PjwvdGl0bGVzPjxwZXJpb2RpY2FsPjxmdWxsLXRpdGxlPk5hdCBSZXYgQ2FuY2VyPC9mdWxsLXRp

dGxlPjxhYmJyLTE+TmF0dXJlIHJldmlld3MuIENhbmNlcjwvYWJici0xPjwvcGVyaW9kaWNhbD48

YWx0LXBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+TmF0IFJldiBDYW5jZXI8L2Z1bGwtdGl0bGU+PGFi

YnItMT5OYXR1cmUgcmV2aWV3cy4gQ2FuY2VyPC9hYmJyLTE+PC9hbHQtcGVyaW9kaWNhbD48cGFn

ZXM+ODUtOTU8L3BhZ2VzPjx2b2x1bWU+MTE8L3ZvbHVtZT48bnVtYmVyPjI8L251bWJlcj48ZWRp

dGlvbj4yMDExLzAxLzI1PC9lZGl0aW9uPjxrZXl3b3Jkcz48a2V5d29yZD5DZWxsIFRyYW5zZm9y

bWF0aW9uLCBOZW9wbGFzdGljL2dlbmV0aWNzLyBtZXRhYm9saXNtPC9rZXl3b3JkPjxrZXl3b3Jk

PkdlbmUgRXhwcmVzc2lvbiBSZWd1bGF0aW9uLCBOZW9wbGFzdGljPC9rZXl3b3JkPjxrZXl3b3Jk

PkdlbmUgUmVndWxhdG9yeSBOZXR3b3Jrczwva2V5d29yZD48a2V5d29yZD5IdW1hbnM8L2tleXdv

cmQ+PGtleXdvcmQ+SW50cmFjZWxsdWxhciBTaWduYWxpbmcgUGVwdGlkZXMgYW5kIFByb3RlaW5z

L21ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+TmVvcGxhc21zL2dlbmV0aWNzLyBtZXRhYm9s

aXNtPC9rZXl3b3JkPjxrZXl3b3JkPk94aWRhdGlvbi1SZWR1Y3Rpb248L2tleXdvcmQ+PGtleXdv

cmQ+U2lnbmFsIFRyYW5zZHVjdGlvbjwva2V5d29yZD48a2V5d29yZD5UcmFuc2NyaXB0aW9uIEZh

Y3RvcnMvbWV0YWJvbGlzbTwva2V5d29yZD48L2tleXdvcmRzPjxkYXRlcz48eWVhcj4yMDExPC95

ZWFyPjxwdWItZGF0ZXM+PGRhdGU+RmViPC9kYXRlPjwvcHViLWRhdGVzPjwvZGF0ZXM+PGlzYm4+

MTQ3NC0xNzY4IChFbGVjdHJvbmljKSYjeEQ7MTQ3NC0xNzVYIChMaW5raW5nKTwvaXNibj48YWNj

ZXNzaW9uLW51bT4yMTI1ODM5NDwvYWNjZXNzaW9uLW51bT48dXJscz48L3VybHM+PGVsZWN0cm9u

aWMtcmVzb3VyY2UtbnVtPjEwLjEwMzgvbnJjMjk4MTwvZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+

PHJlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj5OTE08L3JlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj48

bGFuZ3VhZ2U+ZW5nPC9sYW5ndWFnZT48L3JlY29yZD48L0NpdGU+PC9FbmROb3RlPgB=

ADDIN EN.CITE.DATA [67-70]. В отличие от нормальных клеток, в которых уровень GSH снижался по мере увеличения количества клеток (т.н. контактное торможение), уровень GSH в опухолевых клеток был постоянно высоким PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IdXR0ZXI8L0F1dGhvcj48WWVhcj4xOTk3PC9ZZWFyPjxS

ZWNOdW0+MjMwPC9SZWNOdW0+PERpc3BsYXlUZXh0Pls3MV08L0Rpc3BsYXlUZXh0PjxyZWNvcmQ+

PHJlYy1udW1iZXI+MjMwPC9yZWMtbnVtYmVyPjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVOIiBk

Yi1pZD0idzJ3ZnhhZmU2dmE5ejVlZXYybDU1YWE4c3hzYTU5OWVldjJzIj4yMzA8L2tleT48L2Zv

cmVpZ24ta2V5cz48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+

PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPkh1dHRlciwgRC4gRS48L2F1dGhvcj48YXV0

aG9yPlRpbGwsIEIuIEcuPC9hdXRob3I+PGF1dGhvcj5HcmVlbmUsIEouIEouPC9hdXRob3I+PC9h

dXRob3JzPjwvY29udHJpYnV0b3JzPjxhdXRoLWFkZHJlc3M+RGVwYXJ0bWVudCBvZiBCaW9sb2d5

LCBDYXRob2xpYyBVbml2ZXJzaXR5IG9mIEFtZXJpY2EsIFdhc2hpbmd0b24sIERDIDIwMDY0LCBV

U0EuPC9hdXRoLWFkZHJlc3M+PHRpdGxlcz48dGl0bGU+UmVkb3ggc3RhdGUgY2hhbmdlcyBpbiBk

ZW5zaXR5LWRlcGVuZGVudCByZWd1bGF0aW9uIG9mIHByb2xpZmVyYXRpb248L3RpdGxlPjxzZWNv

bmRhcnktdGl0bGU+RXhwIENlbGwgUmVzPC9zZWNvbmRhcnktdGl0bGU+PGFsdC10aXRsZT5FeHBl

cmltZW50YWwgY2VsbCByZXNlYXJjaDwvYWx0LXRpdGxlPjwvdGl0bGVzPjxwZXJpb2RpY2FsPjxm

dWxsLXRpdGxlPkV4cCBDZWxsIFJlczwvZnVsbC10aXRsZT48YWJici0xPkV4cGVyaW1lbnRhbCBj

ZWxsIHJlc2VhcmNoPC9hYmJyLTE+PC9wZXJpb2RpY2FsPjxhbHQtcGVyaW9kaWNhbD48ZnVsbC10

aXRsZT5FeHAgQ2VsbCBSZXM8L2Z1bGwtdGl0bGU+PGFiYnItMT5FeHBlcmltZW50YWwgY2VsbCBy

ZXNlYXJjaDwvYWJici0xPjwvYWx0LXBlcmlvZGljYWw+PHBhZ2VzPjQzNS04PC9wYWdlcz48dm9s

dW1lPjIzMjwvdm9sdW1lPjxudW1iZXI+MjwvbnVtYmVyPjxlZGl0aW9uPjE5OTcvMDUvMDE8L2Vk

aXRpb24+PGtleXdvcmRzPjxrZXl3b3JkPkFjZXR5bGN5c3RlaW5lL3BoYXJtYWNvbG9neTwva2V5

d29yZD48a2V5d29yZD5CdXRoaW9uaW5lIFN1bGZveGltaW5lL3BoYXJtYWNvbG9neTwva2V5d29y

ZD48a2V5d29yZD5DZWxsIERpdmlzaW9uL2RydWcgZWZmZWN0cy8gcGh5c2lvbG9neTwva2V5d29y

ZD48a2V5d29yZD5DZWxsIExpbmU8L2tleXdvcmQ+PGtleXdvcmQ+Q29udGFjdCBJbmhpYml0aW9u

L3BoeXNpb2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+Rmlicm9ibGFzdHMvY3l0b2xvZ3kvZHJ1ZyBl

ZmZlY3RzL21ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+Rmlicm9zYXJjb21hL21ldGFib2xp

c20vcGF0aG9sb2d5PC9rZXl3b3JkPjxrZXl3b3JkPkdsdXRhdGhpb25lL2NoZW1pc3RyeS8gcGh5

c2lvbG9neTwva2V5d29yZD48a2V5d29yZD5IdW1hbnM8L2tleXdvcmQ+PGtleXdvcmQ+TWFsZTwv

a2V5d29yZD48a2V5d29yZD5OZW9wbGFzbSBQcm90ZWlucy9tZXRhYm9saXNtPC9rZXl3b3JkPjxr

ZXl3b3JkPk94aWRhdGlvbi1SZWR1Y3Rpb248L2tleXdvcmQ+PGtleXdvcmQ+UHJvdGVpbiBCaW5k

aW5nPC9rZXl3b3JkPjxrZXl3b3JkPlB5cnJvbGlkb25lY2FyYm94eWxpYyBBY2lkPC9rZXl3b3Jk

PjxrZXl3b3JkPlRoaWF6b2xlcy9waGFybWFjb2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+VGhpYXpv

bGlkaW5lczwva2V5d29yZD48a2V5d29yZD5UcmFuc2NyaXB0aW9uIEZhY3RvcnMvIG1ldGFib2xp

c208L2tleXdvcmQ+PGtleXdvcmQ+VHVtb3IgQ2VsbHMsIEN1bHR1cmVkPC9rZXl3b3JkPjwva2V5

d29yZHM+PGRhdGVzPjx5ZWFyPjE5OTc8L3llYXI+PHB1Yi1kYXRlcz48ZGF0ZT5NYXkgMTwvZGF0

ZT48L3B1Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjAwMTQtNDgyNyAoUHJpbnQpJiN4RDswMDE0LTQ4

MjcgKExpbmtpbmcpPC9pc2JuPjxhY2Nlc3Npb24tbnVtPjkxNjg4MjM8L2FjY2Vzc2lvbi1udW0+

PHVybHM+PC91cmxzPjxlbGVjdHJvbmljLXJlc291cmNlLW51bT4xMC4xMDA2L2V4Y3IuMTk5Ny4z

NTI3PC9lbGVjdHJvbmljLXJlc291cmNlLW51bT48cmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPk5M

TTwvcmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPjxsYW5ndWFnZT5lbmc8L2xhbmd1YWdlPjwvcmVj

b3JkPjwvQ2l0ZT48L0VuZE5vdGU+AG==

ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IdXR0ZXI8L0F1dGhvcj48WWVhcj4xOTk3PC9ZZWFyPjxS

ZWNOdW0+MjMwPC9SZWNOdW0+PERpc3BsYXlUZXh0Pls3MV08L0Rpc3BsYXlUZXh0PjxyZWNvcmQ+

PHJlYy1udW1iZXI+MjMwPC9yZWMtbnVtYmVyPjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVOIiBk

Yi1pZD0idzJ3ZnhhZmU2dmE5ejVlZXYybDU1YWE4c3hzYTU5OWVldjJzIj4yMzA8L2tleT48L2Zv

cmVpZ24ta2V5cz48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+

PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPkh1dHRlciwgRC4gRS48L2F1dGhvcj48YXV0

aG9yPlRpbGwsIEIuIEcuPC9hdXRob3I+PGF1dGhvcj5HcmVlbmUsIEouIEouPC9hdXRob3I+PC9h

dXRob3JzPjwvY29udHJpYnV0b3JzPjxhdXRoLWFkZHJlc3M+RGVwYXJ0bWVudCBvZiBCaW9sb2d5

LCBDYXRob2xpYyBVbml2ZXJzaXR5IG9mIEFtZXJpY2EsIFdhc2hpbmd0b24sIERDIDIwMDY0LCBV

U0EuPC9hdXRoLWFkZHJlc3M+PHRpdGxlcz48dGl0bGU+UmVkb3ggc3RhdGUgY2hhbmdlcyBpbiBk

ZW5zaXR5LWRlcGVuZGVudCByZWd1bGF0aW9uIG9mIHByb2xpZmVyYXRpb248L3RpdGxlPjxzZWNv

bmRhcnktdGl0bGU+RXhwIENlbGwgUmVzPC9zZWNvbmRhcnktdGl0bGU+PGFsdC10aXRsZT5FeHBl

cmltZW50YWwgY2VsbCByZXNlYXJjaDwvYWx0LXRpdGxlPjwvdGl0bGVzPjxwZXJpb2RpY2FsPjxm

dWxsLXRpdGxlPkV4cCBDZWxsIFJlczwvZnVsbC10aXRsZT48YWJici0xPkV4cGVyaW1lbnRhbCBj

ZWxsIHJlc2VhcmNoPC9hYmJyLTE+PC9wZXJpb2RpY2FsPjxhbHQtcGVyaW9kaWNhbD48ZnVsbC10

aXRsZT5FeHAgQ2VsbCBSZXM8L2Z1bGwtdGl0bGU+PGFiYnItMT5FeHBlcmltZW50YWwgY2VsbCBy

ZXNlYXJjaDwvYWJici0xPjwvYWx0LXBlcmlvZGljYWw+PHBhZ2VzPjQzNS04PC9wYWdlcz48dm9s

dW1lPjIzMjwvdm9sdW1lPjxudW1iZXI+MjwvbnVtYmVyPjxlZGl0aW9uPjE5OTcvMDUvMDE8L2Vk

aXRpb24+PGtleXdvcmRzPjxrZXl3b3JkPkFjZXR5bGN5c3RlaW5lL3BoYXJtYWNvbG9neTwva2V5

d29yZD48a2V5d29yZD5CdXRoaW9uaW5lIFN1bGZveGltaW5lL3BoYXJtYWNvbG9neTwva2V5d29y

ZD48a2V5d29yZD5DZWxsIERpdmlzaW9uL2RydWcgZWZmZWN0cy8gcGh5c2lvbG9neTwva2V5d29y

ZD48a2V5d29yZD5DZWxsIExpbmU8L2tleXdvcmQ+PGtleXdvcmQ+Q29udGFjdCBJbmhpYml0aW9u

L3BoeXNpb2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+Rmlicm9ibGFzdHMvY3l0b2xvZ3kvZHJ1ZyBl

ZmZlY3RzL21ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+Rmlicm9zYXJjb21hL21ldGFib2xp

c20vcGF0aG9sb2d5PC9rZXl3b3JkPjxrZXl3b3JkPkdsdXRhdGhpb25lL2NoZW1pc3RyeS8gcGh5

c2lvbG9neTwva2V5d29yZD48a2V5d29yZD5IdW1hbnM8L2tleXdvcmQ+PGtleXdvcmQ+TWFsZTwv

a2V5d29yZD48a2V5d29yZD5OZW9wbGFzbSBQcm90ZWlucy9tZXRhYm9saXNtPC9rZXl3b3JkPjxr

ZXl3b3JkPk94aWRhdGlvbi1SZWR1Y3Rpb248L2tleXdvcmQ+PGtleXdvcmQ+UHJvdGVpbiBCaW5k

aW5nPC9rZXl3b3JkPjxrZXl3b3JkPlB5cnJvbGlkb25lY2FyYm94eWxpYyBBY2lkPC9rZXl3b3Jk

PjxrZXl3b3JkPlRoaWF6b2xlcy9waGFybWFjb2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+VGhpYXpv

bGlkaW5lczwva2V5d29yZD48a2V5d29yZD5UcmFuc2NyaXB0aW9uIEZhY3RvcnMvIG1ldGFib2xp

c208L2tleXdvcmQ+PGtleXdvcmQ+VHVtb3IgQ2VsbHMsIEN1bHR1cmVkPC9rZXl3b3JkPjwva2V5

d29yZHM+PGRhdGVzPjx5ZWFyPjE5OTc8L3llYXI+PHB1Yi1kYXRlcz48ZGF0ZT5NYXkgMTwvZGF0

ZT48L3B1Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjAwMTQtNDgyNyAoUHJpbnQpJiN4RDswMDE0LTQ4

MjcgKExpbmtpbmcpPC9pc2JuPjxhY2Nlc3Npb24tbnVtPjkxNjg4MjM8L2FjY2Vzc2lvbi1udW0+

PHVybHM+PC91cmxzPjxlbGVjdHJvbmljLXJlc291cmNlLW51bT4xMC4xMDA2L2V4Y3IuMTk5Ny4z

NTI3PC9lbGVjdHJvbmljLXJlc291cmNlLW51bT48cmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPk5M

TTwvcmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPjxsYW5ndWFnZT5lbmc8L2xhbmd1YWdlPjwvcmVj

b3JkPjwvQ2l0ZT48L0VuZE5vdGU+AG==

ADDIN EN.CITE.DATA [71]. Вероятно, поэтому опухолевые клетки были невосприимчивы к действию NAC, предшественнику GSH. Обработка клеток карциномы молочной железы с помощью NAC не приводила к восстановлению редокс и формированию G1 блока PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NZW5vbjwvQXV0aG9yPjxZZWFyPjIwMDU8L1llYXI+PFJl

Y051bT4zMDU8L1JlY051bT48RGlzcGxheVRleHQ+WzcyXTwvRGlzcGxheVRleHQ+PHJlY29yZD48

cmVjLW51bWJlcj4zMDU8L3JlYy1udW1iZXI+PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0iRU4iIGRi

LWlkPSJ3MndmeGFmZTZ2YTl6NWVldjJsNTVhYThzeHNhNTk5ZWV2MnMiPjMwNTwva2V5PjwvZm9y

ZWlnbi1rZXlzPjxyZWYtdHlwZSBuYW1lPSJKb3VybmFsIEFydGljbGUiPjE3PC9yZWYtdHlwZT48

Y29udHJpYnV0b3JzPjxhdXRob3JzPjxhdXRob3I+TWVub24sIFMuIEcuPC9hdXRob3I+PGF1dGhv

cj5Db2xlbWFuLCBNLiBDLjwvYXV0aG9yPjxhdXRob3I+V2Fsc2gsIFMuIEEuPC9hdXRob3I+PGF1

dGhvcj5TcGl0eiwgRC4gUi48L2F1dGhvcj48YXV0aG9yPkdvc3dhbWksIFAuIEMuPC9hdXRob3I+

PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjxhdXRoLWFkZHJlc3M+RnJlZSBSYWRpY2FsIGFuZCBS

YWRpYXRpb24gQmlvbG9neSBQcm9ncmFtLCBEZXBhcnRtZW50IG9mIFJhZGlhdGlvbiBPbmNvbG9n

eSwgVW5pdmVyc2l0eSBvZiBJb3dhLCBJb3dhIENpdHksIElBIDUyMjQyLCBVU0EuPC9hdXRoLWFk

ZHJlc3M+PHRpdGxlcz48dGl0bGU+RGlmZmVyZW50aWFsIHN1c2NlcHRpYmlsaXR5IG9mIG5vbm1h

bGlnbmFudCBodW1hbiBicmVhc3QgZXBpdGhlbGlhbCBjZWxscyBhbmQgYnJlYXN0IGNhbmNlciBj

ZWxscyB0byB0aGlvbCBhbnRpb3hpZGFudC1pbmR1Y2VkIEcoMSktZGVsYXk8L3RpdGxlPjxzZWNv

bmRhcnktdGl0bGU+QW50aW94aWQgUmVkb3ggU2lnbmFsPC9zZWNvbmRhcnktdGl0bGU+PGFsdC10

aXRsZT5BbnRpb3hpZGFudHMgJmFtcDsgcmVkb3ggc2lnbmFsaW5nPC9hbHQtdGl0bGU+PC90aXRs

ZXM+PHBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+QW50aW94aWQgUmVkb3ggU2lnbmFsPC9mdWxsLXRp

dGxlPjxhYmJyLTE+QW50aW94aWRhbnRzICZhbXA7IHJlZG94IHNpZ25hbGluZzwvYWJici0xPjwv

cGVyaW9kaWNhbD48YWx0LXBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+QW50aW94aWQgUmVkb3ggU2ln

bmFsPC9mdWxsLXRpdGxlPjxhYmJyLTE+QW50aW94aWRhbnRzICZhbXA7IHJlZG94IHNpZ25hbGlu

ZzwvYWJici0xPjwvYWx0LXBlcmlvZGljYWw+PHBhZ2VzPjcxMS04PC9wYWdlcz48dm9sdW1lPjc8

L3ZvbHVtZT48bnVtYmVyPjUtNjwvbnVtYmVyPjxlZGl0aW9uPjIwMDUvMDUvMTQ8L2VkaXRpb24+

PGtleXdvcmRzPjxrZXl3b3JkPkFjZXR5bGN5c3RlaW5lL3BoYXJtYWNvbG9neTwva2V5d29yZD48

a2V5d29yZD5BbnRpb3hpZGFudHMvIHBoYXJtYWNvbG9neTwva2V5d29yZD48a2V5d29yZD5CcmVh

c3QvIGN5dG9sb2d5L3BhdGhvbG9neTwva2V5d29yZD48a2V5d29yZD5CcmVhc3QgTmVvcGxhc21z

L21ldGFib2xpc20vIHBhdGhvbG9neTwva2V5d29yZD48a2V5d29yZD5DZWxsIEN5Y2xlIFByb3Rl

aW5zL21ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+Q2VsbCBMaW5lPC9rZXl3b3JkPjxrZXl3

b3JkPkVwaXRoZWxpYWwgQ2VsbHMvIGN5dG9sb2d5LyBkcnVnIGVmZmVjdHMvbWV0YWJvbGlzbS9w

YXRob2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+RzEgUGhhc2UvIGRydWcgZWZmZWN0czwva2V5d29y

ZD48a2V5d29yZD5IdW1hbnM8L2tleXdvcmQ+PGtleXdvcmQ+T3hpZGF0aW9uLVJlZHVjdGlvbi9k

cnVnIGVmZmVjdHM8L2tleXdvcmQ+PGtleXdvcmQ+U3VsZmh5ZHJ5bCBDb21wb3VuZHMvIHBoYXJt

YWNvbG9neTwva2V5d29yZD48L2tleXdvcmRzPjxkYXRlcz48eWVhcj4yMDA1PC95ZWFyPjxwdWIt

ZGF0ZXM+PGRhdGU+TWF5LUp1bjwvZGF0ZT48L3B1Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjE1MjMt

MDg2NCAoUHJpbnQpJiN4RDsxNTIzLTA4NjQgKExpbmtpbmcpPC9pc2JuPjxhY2Nlc3Npb24tbnVt

PjE1ODkwMDE3PC9hY2Nlc3Npb24tbnVtPjx1cmxzPjwvdXJscz48ZWxlY3Ryb25pYy1yZXNvdXJj

ZS1udW0+MTAuMTA4OS9hcnMuMjAwNS43LjcxMTwvZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+PHJl

bW90ZS1kYXRhYmFzZS1wcm92aWRlcj5OTE08L3JlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj48bGFu

Z3VhZ2U+ZW5nPC9sYW5ndWFnZT48L3JlY29yZD48L0NpdGU+PC9FbmROb3RlPgB=

ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NZW5vbjwvQXV0aG9yPjxZZWFyPjIwMDU8L1llYXI+PFJl

Y051bT4zMDU8L1JlY051bT48RGlzcGxheVRleHQ+WzcyXTwvRGlzcGxheVRleHQ+PHJlY29yZD48

cmVjLW51bWJlcj4zMDU8L3JlYy1udW1iZXI+PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0iRU4iIGRi

LWlkPSJ3MndmeGFmZTZ2YTl6NWVldjJsNTVhYThzeHNhNTk5ZWV2MnMiPjMwNTwva2V5PjwvZm9y

ZWlnbi1rZXlzPjxyZWYtdHlwZSBuYW1lPSJKb3VybmFsIEFydGljbGUiPjE3PC9yZWYtdHlwZT48

Y29udHJpYnV0b3JzPjxhdXRob3JzPjxhdXRob3I+TWVub24sIFMuIEcuPC9hdXRob3I+PGF1dGhv

cj5Db2xlbWFuLCBNLiBDLjwvYXV0aG9yPjxhdXRob3I+V2Fsc2gsIFMuIEEuPC9hdXRob3I+PGF1

dGhvcj5TcGl0eiwgRC4gUi48L2F1dGhvcj48YXV0aG9yPkdvc3dhbWksIFAuIEMuPC9hdXRob3I+

PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjxhdXRoLWFkZHJlc3M+RnJlZSBSYWRpY2FsIGFuZCBS

YWRpYXRpb24gQmlvbG9neSBQcm9ncmFtLCBEZXBhcnRtZW50IG9mIFJhZGlhdGlvbiBPbmNvbG9n

eSwgVW5pdmVyc2l0eSBvZiBJb3dhLCBJb3dhIENpdHksIElBIDUyMjQyLCBVU0EuPC9hdXRoLWFk

ZHJlc3M+PHRpdGxlcz48dGl0bGU+RGlmZmVyZW50aWFsIHN1c2NlcHRpYmlsaXR5IG9mIG5vbm1h

bGlnbmFudCBodW1hbiBicmVhc3QgZXBpdGhlbGlhbCBjZWxscyBhbmQgYnJlYXN0IGNhbmNlciBj

ZWxscyB0byB0aGlvbCBhbnRpb3hpZGFudC1pbmR1Y2VkIEcoMSktZGVsYXk8L3RpdGxlPjxzZWNv

bmRhcnktdGl0bGU+QW50aW94aWQgUmVkb3ggU2lnbmFsPC9zZWNvbmRhcnktdGl0bGU+PGFsdC10

aXRsZT5BbnRpb3hpZGFudHMgJmFtcDsgcmVkb3ggc2lnbmFsaW5nPC9hbHQtdGl0bGU+PC90aXRs

ZXM+PHBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+QW50aW94aWQgUmVkb3ggU2lnbmFsPC9mdWxsLXRp

dGxlPjxhYmJyLTE+QW50aW94aWRhbnRzICZhbXA7IHJlZG94IHNpZ25hbGluZzwvYWJici0xPjwv

cGVyaW9kaWNhbD48YWx0LXBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+QW50aW94aWQgUmVkb3ggU2ln

bmFsPC9mdWxsLXRpdGxlPjxhYmJyLTE+QW50aW94aWRhbnRzICZhbXA7IHJlZG94IHNpZ25hbGlu

ZzwvYWJici0xPjwvYWx0LXBlcmlvZGljYWw+PHBhZ2VzPjcxMS04PC9wYWdlcz48dm9sdW1lPjc8

L3ZvbHVtZT48bnVtYmVyPjUtNjwvbnVtYmVyPjxlZGl0aW9uPjIwMDUvMDUvMTQ8L2VkaXRpb24+

PGtleXdvcmRzPjxrZXl3b3JkPkFjZXR5bGN5c3RlaW5lL3BoYXJtYWNvbG9neTwva2V5d29yZD48

a2V5d29yZD5BbnRpb3hpZGFudHMvIHBoYXJtYWNvbG9neTwva2V5d29yZD48a2V5d29yZD5CcmVh

c3QvIGN5dG9sb2d5L3BhdGhvbG9neTwva2V5d29yZD48a2V5d29yZD5CcmVhc3QgTmVvcGxhc21z

L21ldGFib2xpc20vIHBhdGhvbG9neTwva2V5d29yZD48a2V5d29yZD5DZWxsIEN5Y2xlIFByb3Rl

aW5zL21ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+Q2VsbCBMaW5lPC9rZXl3b3JkPjxrZXl3

b3JkPkVwaXRoZWxpYWwgQ2VsbHMvIGN5dG9sb2d5LyBkcnVnIGVmZmVjdHMvbWV0YWJvbGlzbS9w

YXRob2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+RzEgUGhhc2UvIGRydWcgZWZmZWN0czwva2V5d29y

ZD48a2V5d29yZD5IdW1hbnM8L2tleXdvcmQ+PGtleXdvcmQ+T3hpZGF0aW9uLVJlZHVjdGlvbi9k

cnVnIGVmZmVjdHM8L2tleXdvcmQ+PGtleXdvcmQ+U3VsZmh5ZHJ5bCBDb21wb3VuZHMvIHBoYXJt

YWNvbG9neTwva2V5d29yZD48L2tleXdvcmRzPjxkYXRlcz48eWVhcj4yMDA1PC95ZWFyPjxwdWIt

ZGF0ZXM+PGRhdGU+TWF5LUp1bjwvZGF0ZT48L3B1Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjE1MjMt

MDg2NCAoUHJpbnQpJiN4RDsxNTIzLTA4NjQgKExpbmtpbmcpPC9pc2JuPjxhY2Nlc3Npb24tbnVt

PjE1ODkwMDE3PC9hY2Nlc3Npb24tbnVtPjx1cmxzPjwvdXJscz48ZWxlY3Ryb25pYy1yZXNvdXJj

ZS1udW0+MTAuMTA4OS9hcnMuMjAwNS43LjcxMTwvZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+PHJl

bW90ZS1kYXRhYmFzZS1wcm92aWRlcj5OTE08L3JlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj48bGFu

Z3VhZ2U+ZW5nPC9sYW5ndWFnZT48L3JlY29yZD48L0NpdGU+PC9FbmROb3RlPgB=

ADDIN EN.CITE.DATA [72]. Снижение внутриклеточного уровня GSH за счет ингибирования -глутамилцистеинсинтетазы с помощью DL-бутионин-S,R-сульфоксимина (BSO), приводило к смещению внутриклеточного редокс-статуса в более окисленное состояние и аресту клеточной пролиферации PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MZXVuZzwvQXV0aG9yPjxZZWFyPjE5OTM8L1llYXI+PFJl

Y051bT4yNTwvUmVjTnVtPjxEaXNwbGF5VGV4dD5bNzNdPC9EaXNwbGF5VGV4dD48cmVjb3JkPjxy

ZWMtbnVtYmVyPjI1PC9yZWMtbnVtYmVyPjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVOIiBkYi1p

ZD0idzJ3ZnhhZmU2dmE5ejVlZXYybDU1YWE4c3hzYTU5OWVldjJzIj4yNTwva2V5PjwvZm9yZWln

bi1rZXlzPjxyZWYtdHlwZSBuYW1lPSJKb3VybmFsIEFydGljbGUiPjE3PC9yZWYtdHlwZT48Y29u

dHJpYnV0b3JzPjxhdXRob3JzPjxhdXRob3I+TGV1bmcsIFMuIFcuPC9hdXRob3I+PGF1dGhvcj5N

aXRjaGVsbCwgSi4gQi48L2F1dGhvcj48YXV0aG9yPmFsLU5hYnVsc2ksIEkuPC9hdXRob3I+PGF1

dGhvcj5GcmllZG1hbiwgTi48L2F1dGhvcj48YXV0aG9yPk5ld3NvbWUsIEouPC9hdXRob3I+PGF1

dGhvcj5CZWxsZGVncnVuLCBBLjwvYXV0aG9yPjxhdXRob3I+S2FzaWQsIFUuPC9hdXRob3I+PC9h

dXRob3JzPjwvY29udHJpYnV0b3JzPjxhdXRoLWFkZHJlc3M+RGVwYXJ0bWVudCBvZiBSYWRpYXRp

b24gTWVkaWNpbmUsIExvbWJhcmRpIENhbmNlciBDZW50ZXIsIEdlb3JnZXRvd24gVW5pdmVyc2l0

eSwgV2FzaGluZ3RvbiwgREMgMjAwMDcuPC9hdXRoLWFkZHJlc3M+PHRpdGxlcz48dGl0bGU+RWZm

ZWN0IG9mIEwtYnV0aGlvbmluZSBzdWxmb3hpbWluZSBvbiB0aGUgcmFkaWF0aW9uIHJlc3BvbnNl

IG9mIGh1bWFuIHJlbmFsIGNhcmNpbm9tYSBjZWxsIGxpbmVzPC90aXRsZT48c2Vjb25kYXJ5LXRp

dGxlPkNhbmNlcjwvc2Vjb25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+Q2FuY2VyPC9hbHQtdGl0bGU+

PC90aXRsZXM+PHBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+Q2FuY2VyPC9mdWxsLXRpdGxlPjxhYmJy

LTE+Q2FuY2VyPC9hYmJyLTE+PC9wZXJpb2RpY2FsPjxhbHQtcGVyaW9kaWNhbD48ZnVsbC10aXRs

ZT5DYW5jZXI8L2Z1bGwtdGl0bGU+PGFiYnItMT5DYW5jZXI8L2FiYnItMT48L2FsdC1wZXJpb2Rp

Y2FsPjxwYWdlcz4yMjc2LTg1PC9wYWdlcz48dm9sdW1lPjcxPC92b2x1bWU+PG51bWJlcj43PC9u

dW1iZXI+PGVkaXRpb24+MTk5My8wNC8wMTwvZWRpdGlvbj48a2V5d29yZHM+PGtleXdvcmQ+QW5p

bWFsczwva2V5d29yZD48a2V5d29yZD5CdXRoaW9uaW5lIFN1bGZveGltaW5lPC9rZXl3b3JkPjxr

ZXl3b3JkPkNhcmNpbm9tYSwgUmVuYWwgQ2VsbC9tZXRhYm9saXNtL3BhdGhvbG9neS8gcmFkaW90

aGVyYXB5PC9rZXl3b3JkPjxrZXl3b3JkPkNlbGwgQWRoZXNpb24vcGh5c2lvbG9neTwva2V5d29y

ZD48a2V5d29yZD5DZWxsIERpdmlzaW9uL3BoeXNpb2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+Q2Vs

bCBTdXJ2aXZhbC9waHlzaW9sb2d5PC9rZXl3b3JkPjxrZXl3b3JkPkdsdXRhbWF0ZS1DeXN0ZWlu

ZSBMaWdhc2UvYW50YWdvbmlzdHMgJmFtcDsgaW5oaWJpdG9yczwva2V5d29yZD48a2V5d29yZD5H

bHV0YXRoaW9uZS9kZWZpY2llbmN5L21ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+SHVtYW5z

PC9rZXl3b3JkPjxrZXl3b3JkPktpZG5leSBOZW9wbGFzbXMvbWV0YWJvbGlzbS9wYXRob2xvZ3kv

IHJhZGlvdGhlcmFweTwva2V5d29yZD48a2V5d29yZD5NYWxlPC9rZXl3b3JkPjxrZXl3b3JkPk1l

dGhpb25pbmUgU3VsZm94aW1pbmUvIGFuYWxvZ3MgJmFtcDsgZGVyaXZhdGl2ZXMvcGhhcm1hY29s

b2d5PC9rZXl3b3JkPjxrZXl3b3JkPk1pY2U8L2tleXdvcmQ+PGtleXdvcmQ+TWljZSwgSW5icmVk

IEJBTEIgQzwva2V5d29yZD48a2V5d29yZD5NaWNlLCBOdWRlPC9rZXl3b3JkPjxrZXl3b3JkPlBo

ZW5vdHlwZTwva2V5d29yZD48a2V5d29yZD5SYWRpYXRpb24tU2Vuc2l0aXppbmcgQWdlbnRzLyBw

aGFybWFjb2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+VHVtb3IgQ2VsbHMsIEN1bHR1cmVkL2RydWcg

ZWZmZWN0czwva2V5d29yZD48L2tleXdvcmRzPjxkYXRlcz48eWVhcj4xOTkzPC95ZWFyPjxwdWIt

ZGF0ZXM+PGRhdGU+QXByIDE8L2RhdGU+PC9wdWItZGF0ZXM+PC9kYXRlcz48aXNibj4wMDA4LTU0

M1ggKFByaW50KSYjeEQ7MDAwOC01NDNYIChMaW5raW5nKTwvaXNibj48YWNjZXNzaW9uLW51bT44

MDk1ODQ4PC9hY2Nlc3Npb24tbnVtPjx1cmxzPjwvdXJscz48cmVtb3RlLWRhdGFiYXNlLXByb3Zp

ZGVyPk5MTTwvcmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPjxsYW5ndWFnZT5lbmc8L2xhbmd1YWdl

PjwvcmVjb3JkPjwvQ2l0ZT48L0VuZE5vdGU+

ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MZXVuZzwvQXV0aG9yPjxZZWFyPjE5OTM8L1llYXI+PFJl

Y051bT4yNTwvUmVjTnVtPjxEaXNwbGF5VGV4dD5bNzNdPC9EaXNwbGF5VGV4dD48cmVjb3JkPjxy

ZWMtbnVtYmVyPjI1PC9yZWMtbnVtYmVyPjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVOIiBkYi1p

ZD0idzJ3ZnhhZmU2dmE5ejVlZXYybDU1YWE4c3hzYTU5OWVldjJzIj4yNTwva2V5PjwvZm9yZWln

bi1rZXlzPjxyZWYtdHlwZSBuYW1lPSJKb3VybmFsIEFydGljbGUiPjE3PC9yZWYtdHlwZT48Y29u

dHJpYnV0b3JzPjxhdXRob3JzPjxhdXRob3I+TGV1bmcsIFMuIFcuPC9hdXRob3I+PGF1dGhvcj5N

aXRjaGVsbCwgSi4gQi48L2F1dGhvcj48YXV0aG9yPmFsLU5hYnVsc2ksIEkuPC9hdXRob3I+PGF1

dGhvcj5GcmllZG1hbiwgTi48L2F1dGhvcj48YXV0aG9yPk5ld3NvbWUsIEouPC9hdXRob3I+PGF1

dGhvcj5CZWxsZGVncnVuLCBBLjwvYXV0aG9yPjxhdXRob3I+S2FzaWQsIFUuPC9hdXRob3I+PC9h

dXRob3JzPjwvY29udHJpYnV0b3JzPjxhdXRoLWFkZHJlc3M+RGVwYXJ0bWVudCBvZiBSYWRpYXRp

b24gTWVkaWNpbmUsIExvbWJhcmRpIENhbmNlciBDZW50ZXIsIEdlb3JnZXRvd24gVW5pdmVyc2l0

eSwgV2FzaGluZ3RvbiwgREMgMjAwMDcuPC9hdXRoLWFkZHJlc3M+PHRpdGxlcz48dGl0bGU+RWZm

ZWN0IG9mIEwtYnV0aGlvbmluZSBzdWxmb3hpbWluZSBvbiB0aGUgcmFkaWF0aW9uIHJlc3BvbnNl

IG9mIGh1bWFuIHJlbmFsIGNhcmNpbm9tYSBjZWxsIGxpbmVzPC90aXRsZT48c2Vjb25kYXJ5LXRp

dGxlPkNhbmNlcjwvc2Vjb25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+Q2FuY2VyPC9hbHQtdGl0bGU+

PC90aXRsZXM+PHBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+Q2FuY2VyPC9mdWxsLXRpdGxlPjxhYmJy

LTE+Q2FuY2VyPC9hYmJyLTE+PC9wZXJpb2RpY2FsPjxhbHQtcGVyaW9kaWNhbD48ZnVsbC10aXRs

ZT5DYW5jZXI8L2Z1bGwtdGl0bGU+PGFiYnItMT5DYW5jZXI8L2FiYnItMT48L2FsdC1wZXJpb2Rp

Y2FsPjxwYWdlcz4yMjc2LTg1PC9wYWdlcz48dm9sdW1lPjcxPC92b2x1bWU+PG51bWJlcj43PC9u

dW1iZXI+PGVkaXRpb24+MTk5My8wNC8wMTwvZWRpdGlvbj48a2V5d29yZHM+PGtleXdvcmQ+QW5p

bWFsczwva2V5d29yZD48a2V5d29yZD5CdXRoaW9uaW5lIFN1bGZveGltaW5lPC9rZXl3b3JkPjxr

ZXl3b3JkPkNhcmNpbm9tYSwgUmVuYWwgQ2VsbC9tZXRhYm9saXNtL3BhdGhvbG9neS8gcmFkaW90

aGVyYXB5PC9rZXl3b3JkPjxrZXl3b3JkPkNlbGwgQWRoZXNpb24vcGh5c2lvbG9neTwva2V5d29y

ZD48a2V5d29yZD5DZWxsIERpdmlzaW9uL3BoeXNpb2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+Q2Vs

bCBTdXJ2aXZhbC9waHlzaW9sb2d5PC9rZXl3b3JkPjxrZXl3b3JkPkdsdXRhbWF0ZS1DeXN0ZWlu

ZSBMaWdhc2UvYW50YWdvbmlzdHMgJmFtcDsgaW5oaWJpdG9yczwva2V5d29yZD48a2V5d29yZD5H

bHV0YXRoaW9uZS9kZWZpY2llbmN5L21ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+SHVtYW5z

PC9rZXl3b3JkPjxrZXl3b3JkPktpZG5leSBOZW9wbGFzbXMvbWV0YWJvbGlzbS9wYXRob2xvZ3kv

IHJhZGlvdGhlcmFweTwva2V5d29yZD48a2V5d29yZD5NYWxlPC9rZXl3b3JkPjxrZXl3b3JkPk1l

dGhpb25pbmUgU3VsZm94aW1pbmUvIGFuYWxvZ3MgJmFtcDsgZGVyaXZhdGl2ZXMvcGhhcm1hY29s

b2d5PC9rZXl3b3JkPjxrZXl3b3JkPk1pY2U8L2tleXdvcmQ+PGtleXdvcmQ+TWljZSwgSW5icmVk

IEJBTEIgQzwva2V5d29yZD48a2V5d29yZD5NaWNlLCBOdWRlPC9rZXl3b3JkPjxrZXl3b3JkPlBo

ZW5vdHlwZTwva2V5d29yZD48a2V5d29yZD5SYWRpYXRpb24tU2Vuc2l0aXppbmcgQWdlbnRzLyBw

aGFybWFjb2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+VHVtb3IgQ2VsbHMsIEN1bHR1cmVkL2RydWcg

ZWZmZWN0czwva2V5d29yZD48L2tleXdvcmRzPjxkYXRlcz48eWVhcj4xOTkzPC95ZWFyPjxwdWIt

ZGF0ZXM+PGRhdGU+QXByIDE8L2RhdGU+PC9wdWItZGF0ZXM+PC9kYXRlcz48aXNibj4wMDA4LTU0

M1ggKFByaW50KSYjeEQ7MDAwOC01NDNYIChMaW5raW5nKTwvaXNibj48YWNjZXNzaW9uLW51bT44

MDk1ODQ4PC9hY2Nlc3Npb24tbnVtPjx1cmxzPjwvdXJscz48cmVtb3RlLWRhdGFiYXNlLXByb3Zp

ZGVyPk5MTTwvcmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPjxsYW5ndWFnZT5lbmc8L2xhbmd1YWdl

PjwvcmVjb3JkPjwvQ2l0ZT48L0VuZE5vdGU+

ADDIN EN.CITE.DATA [73].

Активность антиоксидантных ферментов в опухолевых клетках часто понижена по сравнению с нормальными клетками того же типа что, вероятно, является одной из причин активной пролиферации опухолевых клеток. Например, активность CuZnСОД и MnСОД в нормальных клетках печени мыши составляла, соответственно, 122 и 35 ед/мг, в то время как, в клетках гепатомы активность CuZnСОД падала до 40 ед/мг, а активность MnСОД вообще не определялась ADDIN EN.CITE <EndNote><Cite><Author>Oberley</Author><Year>1979</Year><RecNum>95</RecNum><DisplayText>[74]</DisplayText><record><rec-number>95</rec-number><foreign-keys><key app="EN" db-id="w2wfxafe6va9z5eev2l55aa8sxsa599eev2s">95</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Oberley, L. W.</author><author>Buettner, G. R.</author></authors></contributors><titles><title>Role of superoxide dismutase in cancer: a review</title><secondary-title>Cancer Res</secondary-title><alt-title>Cancer research</alt-title></titles><periodical><full-title>Cancer Res</full-title><abbr-1>Cancer research</abbr-1></periodical><alt-periodical><full-title>Cancer Res</full-title><abbr-1>Cancer research</abbr-1></alt-periodical><pages>1141-9</pages><volume>39</volume><number>4</number><edition>1979/04/01</edition><keywords><keyword>Animals</keyword><keyword>Cell Transformation, Neoplastic</keyword><keyword>Cells, Cultured</keyword><keyword>Humans</keyword><keyword>Hydrogen Peroxide/metabolism</keyword><keyword>Iron/metabolism</keyword><keyword>Manganese/metabolism</keyword><keyword>Models, Biological</keyword><keyword>Neoplasms/drug therapy/ metabolism</keyword><keyword>Oxidation-Reduction</keyword><keyword>Sulfhydryl Compounds/metabolism</keyword><keyword>Superoxide Dismutase/ deficiency</keyword><keyword>Superoxides/metabolism/therapeutic use</keyword></keywords><dates><year>1979</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0008-5472 (Print)&#xD;0008-5472 (Linking)</isbn><accession-num>217531</accession-num><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[74]. Повышение экспрессии MnСОД в опухолевых клетках приводило к замедлению опухолевого роста PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5PYmVybGV5PC9BdXRob3I+PFllYXI+MTk3OTwvWWVhcj48

UmVjTnVtPjk1PC9SZWNOdW0+PERpc3BsYXlUZXh0Pls3NC03Nl08L0Rpc3BsYXlUZXh0PjxyZWNv

cmQ+PHJlYy1udW1iZXI+OTU8L3JlYy1udW1iZXI+PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0iRU4i

IGRiLWlkPSJ3MndmeGFmZTZ2YTl6NWVldjJsNTVhYThzeHNhNTk5ZWV2MnMiPjk1PC9rZXk+PC9m

b3JlaWduLWtleXM+PHJlZi10eXBlIG5hbWU9IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBl

Pjxjb250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5PYmVybGV5LCBMLiBXLjwvYXV0aG9yPjxh

dXRob3I+QnVldHRuZXIsIEcuIFIuPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjx0

aXRsZXM+PHRpdGxlPlJvbGUgb2Ygc3VwZXJveGlkZSBkaXNtdXRhc2UgaW4gY2FuY2VyOiBhIHJl

dmlldzwvdGl0bGU+PHNlY29uZGFyeS10aXRsZT5DYW5jZXIgUmVzPC9zZWNvbmRhcnktdGl0bGU+

PGFsdC10aXRsZT5DYW5jZXIgcmVzZWFyY2g8L2FsdC10aXRsZT48L3RpdGxlcz48cGVyaW9kaWNh

bD48ZnVsbC10aXRsZT5DYW5jZXIgUmVzPC9mdWxsLXRpdGxlPjxhYmJyLTE+Q2FuY2VyIHJlc2Vh

cmNoPC9hYmJyLTE+PC9wZXJpb2RpY2FsPjxhbHQtcGVyaW9kaWNhbD48ZnVsbC10aXRsZT5DYW5j

ZXIgUmVzPC9mdWxsLXRpdGxlPjxhYmJyLTE+Q2FuY2VyIHJlc2VhcmNoPC9hYmJyLTE+PC9hbHQt

cGVyaW9kaWNhbD48cGFnZXM+MTE0MS05PC9wYWdlcz48dm9sdW1lPjM5PC92b2x1bWU+PG51bWJl

cj40PC9udW1iZXI+PGVkaXRpb24+MTk3OS8wNC8wMTwvZWRpdGlvbj48a2V5d29yZHM+PGtleXdv

cmQ+QW5pbWFsczwva2V5d29yZD48a2V5d29yZD5DZWxsIFRyYW5zZm9ybWF0aW9uLCBOZW9wbGFz

dGljPC9rZXl3b3JkPjxrZXl3b3JkPkNlbGxzLCBDdWx0dXJlZDwva2V5d29yZD48a2V5d29yZD5I

dW1hbnM8L2tleXdvcmQ+PGtleXdvcmQ+SHlkcm9nZW4gUGVyb3hpZGUvbWV0YWJvbGlzbTwva2V5

d29yZD48a2V5d29yZD5Jcm9uL21ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+TWFuZ2FuZXNl

L21ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+TW9kZWxzLCBCaW9sb2dpY2FsPC9rZXl3b3Jk

PjxrZXl3b3JkPk5lb3BsYXNtcy9kcnVnIHRoZXJhcHkvIG1ldGFib2xpc208L2tleXdvcmQ+PGtl

eXdvcmQ+T3hpZGF0aW9uLVJlZHVjdGlvbjwva2V5d29yZD48a2V5d29yZD5TdWxmaHlkcnlsIENv

bXBvdW5kcy9tZXRhYm9saXNtPC9rZXl3b3JkPjxrZXl3b3JkPlN1cGVyb3hpZGUgRGlzbXV0YXNl

LyBkZWZpY2llbmN5PC9rZXl3b3JkPjxrZXl3b3JkPlN1cGVyb3hpZGVzL21ldGFib2xpc20vdGhl

cmFwZXV0aWMgdXNlPC9rZXl3b3JkPjwva2V5d29yZHM+PGRhdGVzPjx5ZWFyPjE5Nzk8L3llYXI+

PHB1Yi1kYXRlcz48ZGF0ZT5BcHI8L2RhdGU+PC9wdWItZGF0ZXM+PC9kYXRlcz48aXNibj4wMDA4

LTU0NzIgKFByaW50KSYjeEQ7MDAwOC01NDcyIChMaW5raW5nKTwvaXNibj48YWNjZXNzaW9uLW51

bT4yMTc1MzE8L2FjY2Vzc2lvbi1udW0+PHVybHM+PC91cmxzPjxyZW1vdGUtZGF0YWJhc2UtcHJv

dmlkZXI+TkxNPC9yZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+PGxhbmd1YWdlPmVuZzwvbGFuZ3Vh

Z2U+PC9yZWNvcmQ+PC9DaXRlPjxDaXRlPjxBdXRob3I+Wmhvbmc8L0F1dGhvcj48WWVhcj4xOTk3

PC9ZZWFyPjxSZWNOdW0+MTMxPC9SZWNOdW0+PHJlY29yZD48cmVjLW51bWJlcj4xMzE8L3JlYy1u

dW1iZXI+PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0iRU4iIGRiLWlkPSJ3MndmeGFmZTZ2YTl6NWVl

djJsNTVhYThzeHNhNTk5ZWV2MnMiPjEzMTwva2V5PjwvZm9yZWlnbi1rZXlzPjxyZWYtdHlwZSBu

YW1lPSJKb3VybmFsIEFydGljbGUiPjE3PC9yZWYtdHlwZT48Y29udHJpYnV0b3JzPjxhdXRob3Jz

PjxhdXRob3I+WmhvbmcsIFcuPC9hdXRob3I+PGF1dGhvcj5PYmVybGV5LCBMLiBXLjwvYXV0aG9y

PjxhdXRob3I+T2JlcmxleSwgVC4gRC48L2F1dGhvcj48YXV0aG9yPlN0IENsYWlyLCBELiBLLjwv

YXV0aG9yPjwvYXV0aG9ycz48L2NvbnRyaWJ1dG9ycz48YXV0aC1hZGRyZXNzPlJhZGlhdGlvbiBS

ZXNlYXJjaCBMYWJvcmF0b3J5LCBUaGUgVW5pdmVyc2l0eSBvZiBJb3dhLCBJb3dhIENpdHkgNTIy

NDIsIFVTQS48L2F1dGgtYWRkcmVzcz48dGl0bGVzPjx0aXRsZT5TdXBwcmVzc2lvbiBvZiB0aGUg

bWFsaWduYW50IHBoZW5vdHlwZSBvZiBodW1hbiBnbGlvbWEgY2VsbHMgYnkgb3ZlcmV4cHJlc3Np

b24gb2YgbWFuZ2FuZXNlIHN1cGVyb3hpZGUgZGlzbXV0YXNlPC90aXRsZT48c2Vjb25kYXJ5LXRp

dGxlPk9uY29nZW5lPC9zZWNvbmRhcnktdGl0bGU+PGFsdC10aXRsZT5PbmNvZ2VuZTwvYWx0LXRp

dGxlPjwvdGl0bGVzPjxwZXJpb2RpY2FsPjxmdWxsLXRpdGxlPk9uY29nZW5lPC9mdWxsLXRpdGxl

PjxhYmJyLTE+T25jb2dlbmU8L2FiYnItMT48L3BlcmlvZGljYWw+PGFsdC1wZXJpb2RpY2FsPjxm

dWxsLXRpdGxlPk9uY29nZW5lPC9mdWxsLXRpdGxlPjxhYmJyLTE+T25jb2dlbmU8L2FiYnItMT48

L2FsdC1wZXJpb2RpY2FsPjxwYWdlcz40ODEtOTA8L3BhZ2VzPjx2b2x1bWU+MTQ8L3ZvbHVtZT48

bnVtYmVyPjQ8L251bWJlcj48ZWRpdGlvbj4xOTk3LzAxLzMwPC9lZGl0aW9uPjxrZXl3b3Jkcz48

a2V5d29yZD5BbmltYWxzPC9rZXl3b3JkPjxrZXl3b3JkPkNlbGwgRGl2aXNpb248L2tleXdvcmQ+

PGtleXdvcmQ+Q2xvbmUgQ2VsbHM8L2tleXdvcmQ+PGtleXdvcmQ+RE5BIFByaW1lcnM8L2tleXdv

cmQ+PGtleXdvcmQ+R2VuZSBFeHByZXNzaW9uPC9rZXl3b3JkPjxrZXl3b3JkPkdlbmVzLCBUdW1v

ciBTdXBwcmVzc29yPC9rZXl3b3JkPjxrZXl3b3JkPkdsaW9tYS9lbnp5bW9sb2d5LyBwYXRob2xv

Z3k8L2tleXdvcmQ+PGtleXdvcmQ+SHVtYW5zPC9rZXl3b3JkPjxrZXl3b3JkPk1pY2U8L2tleXdv

cmQ+PGtleXdvcmQ+TWljZSwgTnVkZTwva2V5d29yZD48a2V5d29yZD5NaWNyb3Njb3B5LCBJbW11

bm9lbGVjdHJvbjwva2V5d29yZD48a2V5d29yZD5Qb2x5bWVyYXNlIENoYWluIFJlYWN0aW9uPC9r

ZXl3b3JkPjxrZXl3b3JkPlJOQSwgTWVzc2VuZ2VyL2Jpb3N5bnRoZXNpczwva2V5d29yZD48a2V5

d29yZD5SZWNvbWJpbmFudCBQcm90ZWlucy9hbmFseXNpcy9iaW9zeW50aGVzaXM8L2tleXdvcmQ+

PGtleXdvcmQ+U3VwZXJveGlkZSBEaXNtdXRhc2UvYW5hbHlzaXMvIGJpb3N5bnRoZXNpczwva2V5

d29yZD48a2V5d29yZD5UcmFuc2ZlY3Rpb248L2tleXdvcmQ+PGtleXdvcmQ+VHJhbnNwbGFudGF0

aW9uLCBIZXRlcm9sb2dvdXM8L2tleXdvcmQ+PGtleXdvcmQ+VHVtb3IgQ2VsbHMsIEN1bHR1cmVk

PC9rZXl3b3JkPjwva2V5d29yZHM+PGRhdGVzPjx5ZWFyPjE5OTc8L3llYXI+PHB1Yi1kYXRlcz48

ZGF0ZT5KYW4gMzA8L2RhdGU+PC9wdWItZGF0ZXM+PC9kYXRlcz48aXNibj4wOTUwLTkyMzIgKFBy

aW50KSYjeEQ7MDk1MC05MjMyIChMaW5raW5nKTwvaXNibj48YWNjZXNzaW9uLW51bT45MDUzODQ1

PC9hY2Nlc3Npb24tbnVtPjx1cmxzPjwvdXJscz48ZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+MTAu

MTAzOC9zai5vbmMuMTIwMDg1MjwvZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+PHJlbW90ZS1kYXRh

YmFzZS1wcm92aWRlcj5OTE08L3JlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj48bGFuZ3VhZ2U+ZW5n

PC9sYW5ndWFnZT48L3JlY29yZD48L0NpdGU+PENpdGU+PEF1dGhvcj5PYmVybGV5PC9BdXRob3I+

PFllYXI+MTk4OTwvWWVhcj48UmVjTnVtPjIzMjwvUmVjTnVtPjxyZWNvcmQ+PHJlYy1udW1iZXI+

MjMyPC9yZWMtbnVtYmVyPjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVOIiBkYi1pZD0idzJ3Znhh

ZmU2dmE5ejVlZXYybDU1YWE4c3hzYTU5OWVldjJzIj4yMzI8L2tleT48L2ZvcmVpZ24ta2V5cz48

cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+PGNvbnRyaWJ1dG9y

cz48YXV0aG9ycz48YXV0aG9yPk9iZXJsZXksIEwuIFcuPC9hdXRob3I+PGF1dGhvcj5NY0Nvcm1p

Y2ssIE0uIEwuPC9hdXRob3I+PGF1dGhvcj5TaWVycmEtUml2ZXJhLCBFLjwvYXV0aG9yPjxhdXRo

b3I+S2FzZW1zZXQtU3QgQ2xhaXIsIEQuPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3Jz

PjxhdXRoLWFkZHJlc3M+UmFkaWF0aW9uIFJlc2VhcmNoIExhYm9yYXRvcnksIFVuaXZlcnNpdHkg

b2YgSW93YSwgSW93YSBDaXR5IDUyMjQyLjwvYXV0aC1hZGRyZXNzPjx0aXRsZXM+PHRpdGxlPk1h

bmdhbmVzZSBzdXBlcm94aWRlIGRpc211dGFzZSBpbiBub3JtYWwgYW5kIHRyYW5zZm9ybWVkIGh1

bWFuIGVtYnJ5b25pYyBsdW5nIGZpYnJvYmxhc3RzPC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPkZy

ZWUgUmFkaWMgQmlvbCBNZWQ8L3NlY29uZGFyeS10aXRsZT48YWx0LXRpdGxlPkZyZWUgcmFkaWNh

bCBiaW9sb2d5ICZhbXA7IG1lZGljaW5lPC9hbHQtdGl0bGU+PC90aXRsZXM+PHBlcmlvZGljYWw+

PGZ1bGwtdGl0bGU+RnJlZSBSYWRpYyBCaW9sIE1lZDwvZnVsbC10aXRsZT48YWJici0xPkZyZWUg

cmFkaWNhbCBiaW9sb2d5ICZhbXA7IG1lZGljaW5lPC9hYmJyLTE+PC9wZXJpb2RpY2FsPjxhbHQt

cGVyaW9kaWNhbD48ZnVsbC10aXRsZT5GcmVlIFJhZGljIEJpb2wgTWVkPC9mdWxsLXRpdGxlPjxh

YmJyLTE+RnJlZSByYWRpY2FsIGJpb2xvZ3kgJmFtcDsgbWVkaWNpbmU8L2FiYnItMT48L2FsdC1w

ZXJpb2RpY2FsPjxwYWdlcz4zNzktODQ8L3BhZ2VzPjx2b2x1bWU+Njwvdm9sdW1lPjxudW1iZXI+

NDwvbnVtYmVyPjxlZGl0aW9uPjE5ODkvMDEvMDE8L2VkaXRpb24+PGtleXdvcmRzPjxrZXl3b3Jk

PkJsb3R0aW5nLCBXZXN0ZXJuPC9rZXl3b3JkPjxrZXl3b3JkPkNlbGwgTGluZTwva2V5d29yZD48

a2V5d29yZD5DZWxsIFRyYW5zZm9ybWF0aW9uLCBOZW9wbGFzdGljPC9rZXl3b3JkPjxrZXl3b3Jk

PkZpYnJvYmxhc3RzL2Vuenltb2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+SHVtYW5zPC9rZXl3b3Jk

PjxrZXl3b3JkPkx1bmcvZW56eW1vbG9neTwva2V5d29yZD48a2V5d29yZD5TaW1pYW4gdmlydXMg

NDAvZ2VuZXRpY3M8L2tleXdvcmQ+PGtleXdvcmQ+U3VwZXJveGlkZSBEaXNtdXRhc2UvIG1ldGFi

b2xpc208L2tleXdvcmQ+PC9rZXl3b3Jkcz48ZGF0ZXM+PHllYXI+MTk4OTwveWVhcj48L2RhdGVz

Pjxpc2JuPjA4OTEtNTg0OSAoUHJpbnQpJiN4RDswODkxLTU4NDkgKExpbmtpbmcpPC9pc2JuPjxh

Y2Nlc3Npb24tbnVtPjI1NDAwNzA8L2FjY2Vzc2lvbi1udW0+PHVybHM+PC91cmxzPjxyZW1vdGUt

ZGF0YWJhc2UtcHJvdmlkZXI+TkxNPC9yZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+PGxhbmd1YWdl

PmVuZzwvbGFuZ3VhZ2U+PC9yZWNvcmQ+PC9DaXRlPjwvRW5kTm90ZT4A

ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5PYmVybGV5PC9BdXRob3I+PFllYXI+MTk3OTwvWWVhcj48

UmVjTnVtPjk1PC9SZWNOdW0+PERpc3BsYXlUZXh0Pls3NC03Nl08L0Rpc3BsYXlUZXh0PjxyZWNv

cmQ+PHJlYy1udW1iZXI+OTU8L3JlYy1udW1iZXI+PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0iRU4i

IGRiLWlkPSJ3MndmeGFmZTZ2YTl6NWVldjJsNTVhYThzeHNhNTk5ZWV2MnMiPjk1PC9rZXk+PC9m

b3JlaWduLWtleXM+PHJlZi10eXBlIG5hbWU9IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBl

Pjxjb250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5PYmVybGV5LCBMLiBXLjwvYXV0aG9yPjxh

dXRob3I+QnVldHRuZXIsIEcuIFIuPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjx0

aXRsZXM+PHRpdGxlPlJvbGUgb2Ygc3VwZXJveGlkZSBkaXNtdXRhc2UgaW4gY2FuY2VyOiBhIHJl

dmlldzwvdGl0bGU+PHNlY29uZGFyeS10aXRsZT5DYW5jZXIgUmVzPC9zZWNvbmRhcnktdGl0bGU+

PGFsdC10aXRsZT5DYW5jZXIgcmVzZWFyY2g8L2FsdC10aXRsZT48L3RpdGxlcz48cGVyaW9kaWNh

bD48ZnVsbC10aXRsZT5DYW5jZXIgUmVzPC9mdWxsLXRpdGxlPjxhYmJyLTE+Q2FuY2VyIHJlc2Vh

cmNoPC9hYmJyLTE+PC9wZXJpb2RpY2FsPjxhbHQtcGVyaW9kaWNhbD48ZnVsbC10aXRsZT5DYW5j

ZXIgUmVzPC9mdWxsLXRpdGxlPjxhYmJyLTE+Q2FuY2VyIHJlc2VhcmNoPC9hYmJyLTE+PC9hbHQt

cGVyaW9kaWNhbD48cGFnZXM+MTE0MS05PC9wYWdlcz48dm9sdW1lPjM5PC92b2x1bWU+PG51bWJl

cj40PC9udW1iZXI+PGVkaXRpb24+MTk3OS8wNC8wMTwvZWRpdGlvbj48a2V5d29yZHM+PGtleXdv

cmQ+QW5pbWFsczwva2V5d29yZD48a2V5d29yZD5DZWxsIFRyYW5zZm9ybWF0aW9uLCBOZW9wbGFz

dGljPC9rZXl3b3JkPjxrZXl3b3JkPkNlbGxzLCBDdWx0dXJlZDwva2V5d29yZD48a2V5d29yZD5I

dW1hbnM8L2tleXdvcmQ+PGtleXdvcmQ+SHlkcm9nZW4gUGVyb3hpZGUvbWV0YWJvbGlzbTwva2V5

d29yZD48a2V5d29yZD5Jcm9uL21ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+TWFuZ2FuZXNl

L21ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+TW9kZWxzLCBCaW9sb2dpY2FsPC9rZXl3b3Jk

PjxrZXl3b3JkPk5lb3BsYXNtcy9kcnVnIHRoZXJhcHkvIG1ldGFib2xpc208L2tleXdvcmQ+PGtl

eXdvcmQ+T3hpZGF0aW9uLVJlZHVjdGlvbjwva2V5d29yZD48a2V5d29yZD5TdWxmaHlkcnlsIENv

bXBvdW5kcy9tZXRhYm9saXNtPC9rZXl3b3JkPjxrZXl3b3JkPlN1cGVyb3hpZGUgRGlzbXV0YXNl

LyBkZWZpY2llbmN5PC9rZXl3b3JkPjxrZXl3b3JkPlN1cGVyb3hpZGVzL21ldGFib2xpc20vdGhl

cmFwZXV0aWMgdXNlPC9rZXl3b3JkPjwva2V5d29yZHM+PGRhdGVzPjx5ZWFyPjE5Nzk8L3llYXI+

PHB1Yi1kYXRlcz48ZGF0ZT5BcHI8L2RhdGU+PC9wdWItZGF0ZXM+PC9kYXRlcz48aXNibj4wMDA4

LTU0NzIgKFByaW50KSYjeEQ7MDAwOC01NDcyIChMaW5raW5nKTwvaXNibj48YWNjZXNzaW9uLW51

bT4yMTc1MzE8L2FjY2Vzc2lvbi1udW0+PHVybHM+PC91cmxzPjxyZW1vdGUtZGF0YWJhc2UtcHJv

dmlkZXI+TkxNPC9yZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+PGxhbmd1YWdlPmVuZzwvbGFuZ3Vh

Z2U+PC9yZWNvcmQ+PC9DaXRlPjxDaXRlPjxBdXRob3I+Wmhvbmc8L0F1dGhvcj48WWVhcj4xOTk3

PC9ZZWFyPjxSZWNOdW0+MTMxPC9SZWNOdW0+PHJlY29yZD48cmVjLW51bWJlcj4xMzE8L3JlYy1u

dW1iZXI+PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0iRU4iIGRiLWlkPSJ3MndmeGFmZTZ2YTl6NWVl

djJsNTVhYThzeHNhNTk5ZWV2MnMiPjEzMTwva2V5PjwvZm9yZWlnbi1rZXlzPjxyZWYtdHlwZSBu

YW1lPSJKb3VybmFsIEFydGljbGUiPjE3PC9yZWYtdHlwZT48Y29udHJpYnV0b3JzPjxhdXRob3Jz

PjxhdXRob3I+WmhvbmcsIFcuPC9hdXRob3I+PGF1dGhvcj5PYmVybGV5LCBMLiBXLjwvYXV0aG9y

PjxhdXRob3I+T2JlcmxleSwgVC4gRC48L2F1dGhvcj48YXV0aG9yPlN0IENsYWlyLCBELiBLLjwv

YXV0aG9yPjwvYXV0aG9ycz48L2NvbnRyaWJ1dG9ycz48YXV0aC1hZGRyZXNzPlJhZGlhdGlvbiBS

ZXNlYXJjaCBMYWJvcmF0b3J5LCBUaGUgVW5pdmVyc2l0eSBvZiBJb3dhLCBJb3dhIENpdHkgNTIy

NDIsIFVTQS48L2F1dGgtYWRkcmVzcz48dGl0bGVzPjx0aXRsZT5TdXBwcmVzc2lvbiBvZiB0aGUg

bWFsaWduYW50IHBoZW5vdHlwZSBvZiBodW1hbiBnbGlvbWEgY2VsbHMgYnkgb3ZlcmV4cHJlc3Np

b24gb2YgbWFuZ2FuZXNlIHN1cGVyb3hpZGUgZGlzbXV0YXNlPC90aXRsZT48c2Vjb25kYXJ5LXRp

dGxlPk9uY29nZW5lPC9zZWNvbmRhcnktdGl0bGU+PGFsdC10aXRsZT5PbmNvZ2VuZTwvYWx0LXRp

dGxlPjwvdGl0bGVzPjxwZXJpb2RpY2FsPjxmdWxsLXRpdGxlPk9uY29nZW5lPC9mdWxsLXRpdGxl

PjxhYmJyLTE+T25jb2dlbmU8L2FiYnItMT48L3BlcmlvZGljYWw+PGFsdC1wZXJpb2RpY2FsPjxm

dWxsLXRpdGxlPk9uY29nZW5lPC9mdWxsLXRpdGxlPjxhYmJyLTE+T25jb2dlbmU8L2FiYnItMT48

L2FsdC1wZXJpb2RpY2FsPjxwYWdlcz40ODEtOTA8L3BhZ2VzPjx2b2x1bWU+MTQ8L3ZvbHVtZT48

bnVtYmVyPjQ8L251bWJlcj48ZWRpdGlvbj4xOTk3LzAxLzMwPC9lZGl0aW9uPjxrZXl3b3Jkcz48

a2V5d29yZD5BbmltYWxzPC9rZXl3b3JkPjxrZXl3b3JkPkNlbGwgRGl2aXNpb248L2tleXdvcmQ+

PGtleXdvcmQ+Q2xvbmUgQ2VsbHM8L2tleXdvcmQ+PGtleXdvcmQ+RE5BIFByaW1lcnM8L2tleXdv

cmQ+PGtleXdvcmQ+R2VuZSBFeHByZXNzaW9uPC9rZXl3b3JkPjxrZXl3b3JkPkdlbmVzLCBUdW1v

ciBTdXBwcmVzc29yPC9rZXl3b3JkPjxrZXl3b3JkPkdsaW9tYS9lbnp5bW9sb2d5LyBwYXRob2xv

Z3k8L2tleXdvcmQ+PGtleXdvcmQ+SHVtYW5zPC9rZXl3b3JkPjxrZXl3b3JkPk1pY2U8L2tleXdv

cmQ+PGtleXdvcmQ+TWljZSwgTnVkZTwva2V5d29yZD48a2V5d29yZD5NaWNyb3Njb3B5LCBJbW11

bm9lbGVjdHJvbjwva2V5d29yZD48a2V5d29yZD5Qb2x5bWVyYXNlIENoYWluIFJlYWN0aW9uPC9r

ZXl3b3JkPjxrZXl3b3JkPlJOQSwgTWVzc2VuZ2VyL2Jpb3N5bnRoZXNpczwva2V5d29yZD48a2V5

d29yZD5SZWNvbWJpbmFudCBQcm90ZWlucy9hbmFseXNpcy9iaW9zeW50aGVzaXM8L2tleXdvcmQ+

PGtleXdvcmQ+U3VwZXJveGlkZSBEaXNtdXRhc2UvYW5hbHlzaXMvIGJpb3N5bnRoZXNpczwva2V5

d29yZD48a2V5d29yZD5UcmFuc2ZlY3Rpb248L2tleXdvcmQ+PGtleXdvcmQ+VHJhbnNwbGFudGF0

aW9uLCBIZXRlcm9sb2dvdXM8L2tleXdvcmQ+PGtleXdvcmQ+VHVtb3IgQ2VsbHMsIEN1bHR1cmVk

PC9rZXl3b3JkPjwva2V5d29yZHM+PGRhdGVzPjx5ZWFyPjE5OTc8L3llYXI+PHB1Yi1kYXRlcz48

ZGF0ZT5KYW4gMzA8L2RhdGU+PC9wdWItZGF0ZXM+PC9kYXRlcz48aXNibj4wOTUwLTkyMzIgKFBy

aW50KSYjeEQ7MDk1MC05MjMyIChMaW5raW5nKTwvaXNibj48YWNjZXNzaW9uLW51bT45MDUzODQ1

PC9hY2Nlc3Npb24tbnVtPjx1cmxzPjwvdXJscz48ZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+MTAu

MTAzOC9zai5vbmMuMTIwMDg1MjwvZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+PHJlbW90ZS1kYXRh

YmFzZS1wcm92aWRlcj5OTE08L3JlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj48bGFuZ3VhZ2U+ZW5n

PC9sYW5ndWFnZT48L3JlY29yZD48L0NpdGU+PENpdGU+PEF1dGhvcj5PYmVybGV5PC9BdXRob3I+

PFllYXI+MTk4OTwvWWVhcj48UmVjTnVtPjIzMjwvUmVjTnVtPjxyZWNvcmQ+PHJlYy1udW1iZXI+

MjMyPC9yZWMtbnVtYmVyPjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVOIiBkYi1pZD0idzJ3Znhh

ZmU2dmE5ejVlZXYybDU1YWE4c3hzYTU5OWVldjJzIj4yMzI8L2tleT48L2ZvcmVpZ24ta2V5cz48

cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+PGNvbnRyaWJ1dG9y

cz48YXV0aG9ycz48YXV0aG9yPk9iZXJsZXksIEwuIFcuPC9hdXRob3I+PGF1dGhvcj5NY0Nvcm1p

Y2ssIE0uIEwuPC9hdXRob3I+PGF1dGhvcj5TaWVycmEtUml2ZXJhLCBFLjwvYXV0aG9yPjxhdXRo

b3I+S2FzZW1zZXQtU3QgQ2xhaXIsIEQuPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3Jz

PjxhdXRoLWFkZHJlc3M+UmFkaWF0aW9uIFJlc2VhcmNoIExhYm9yYXRvcnksIFVuaXZlcnNpdHkg

b2YgSW93YSwgSW93YSBDaXR5IDUyMjQyLjwvYXV0aC1hZGRyZXNzPjx0aXRsZXM+PHRpdGxlPk1h

bmdhbmVzZSBzdXBlcm94aWRlIGRpc211dGFzZSBpbiBub3JtYWwgYW5kIHRyYW5zZm9ybWVkIGh1

bWFuIGVtYnJ5b25pYyBsdW5nIGZpYnJvYmxhc3RzPC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPkZy

ZWUgUmFkaWMgQmlvbCBNZWQ8L3NlY29uZGFyeS10aXRsZT48YWx0LXRpdGxlPkZyZWUgcmFkaWNh

bCBiaW9sb2d5ICZhbXA7IG1lZGljaW5lPC9hbHQtdGl0bGU+PC90aXRsZXM+PHBlcmlvZGljYWw+

PGZ1bGwtdGl0bGU+RnJlZSBSYWRpYyBCaW9sIE1lZDwvZnVsbC10aXRsZT48YWJici0xPkZyZWUg

cmFkaWNhbCBiaW9sb2d5ICZhbXA7IG1lZGljaW5lPC9hYmJyLTE+PC9wZXJpb2RpY2FsPjxhbHQt

cGVyaW9kaWNhbD48ZnVsbC10aXRsZT5GcmVlIFJhZGljIEJpb2wgTWVkPC9mdWxsLXRpdGxlPjxh

YmJyLTE+RnJlZSByYWRpY2FsIGJpb2xvZ3kgJmFtcDsgbWVkaWNpbmU8L2FiYnItMT48L2FsdC1w

ZXJpb2RpY2FsPjxwYWdlcz4zNzktODQ8L3BhZ2VzPjx2b2x1bWU+Njwvdm9sdW1lPjxudW1iZXI+

NDwvbnVtYmVyPjxlZGl0aW9uPjE5ODkvMDEvMDE8L2VkaXRpb24+PGtleXdvcmRzPjxrZXl3b3Jk

PkJsb3R0aW5nLCBXZXN0ZXJuPC9rZXl3b3JkPjxrZXl3b3JkPkNlbGwgTGluZTwva2V5d29yZD48

a2V5d29yZD5DZWxsIFRyYW5zZm9ybWF0aW9uLCBOZW9wbGFzdGljPC9rZXl3b3JkPjxrZXl3b3Jk

PkZpYnJvYmxhc3RzL2Vuenltb2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+SHVtYW5zPC9rZXl3b3Jk

PjxrZXl3b3JkPkx1bmcvZW56eW1vbG9neTwva2V5d29yZD48a2V5d29yZD5TaW1pYW4gdmlydXMg

NDAvZ2VuZXRpY3M8L2tleXdvcmQ+PGtleXdvcmQ+U3VwZXJveGlkZSBEaXNtdXRhc2UvIG1ldGFi

b2xpc208L2tleXdvcmQ+PC9rZXl3b3Jkcz48ZGF0ZXM+PHllYXI+MTk4OTwveWVhcj48L2RhdGVz

Pjxpc2JuPjA4OTEtNTg0OSAoUHJpbnQpJiN4RDswODkxLTU4NDkgKExpbmtpbmcpPC9pc2JuPjxh

Y2Nlc3Npb24tbnVtPjI1NDAwNzA8L2FjY2Vzc2lvbi1udW0+PHVybHM+PC91cmxzPjxyZW1vdGUt

ZGF0YWJhc2UtcHJvdmlkZXI+TkxNPC9yZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+PGxhbmd1YWdl

PmVuZzwvbGFuZ3VhZ2U+PC9yZWNvcmQ+PC9DaXRlPjwvRW5kTm90ZT4A

ADDIN EN.CITE.DATA [74-76]. Сходные данные были получены для каталазы и некоторых изоформ GPx. Снижение активности ферментов приводило к повышению уровня АФК, усилению пролиферативных процессов, а также способствовало развитию опухолевой трансформации PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CcmlnZWxpdXMtRmxvaGU8L0F1dGhvcj48WWVhcj4yMDA5

PC9ZZWFyPjxSZWNOdW0+NDY0PC9SZWNOdW0+PERpc3BsYXlUZXh0Pls3NywgNzhdPC9EaXNwbGF5

VGV4dD48cmVjb3JkPjxyZWMtbnVtYmVyPjQ2NDwvcmVjLW51bWJlcj48Zm9yZWlnbi1rZXlzPjxr

ZXkgYXBwPSJFTiIgZGItaWQ9Incyd2Z4YWZlNnZhOXo1ZWV2Mmw1NWFhOHN4c2E1OTllZXYycyI+

NDY0PC9rZXk+PC9mb3JlaWduLWtleXM+PHJlZi10eXBlIG5hbWU9IkpvdXJuYWwgQXJ0aWNsZSI+

MTc8L3JlZi10eXBlPjxjb250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5CcmlnZWxpdXMtRmxv

aGUsIFIuPC9hdXRob3I+PGF1dGhvcj5LaXBwLCBBLjwvYXV0aG9yPjwvYXV0aG9ycz48L2NvbnRy

aWJ1dG9ycz48YXV0aC1hZGRyZXNzPkRlcGFydG1lbnQgQmlvY2hlbWlzdHJ5IG9mIE1pY3JvbnV0

cmllbnRzLCBHZXJtYW4gSW5zdGl0dXRlIG9mIEh1bWFuIE51dHJpdGlvbiBQb3RzZGFtLVJlaGJy

dWVja2UsIEFydGh1ci1TY2hldW5lcnQtQWxsZWUgMTE0LTExNiwgRC0xNDU1OCBOdXRoZXRhbCwg

R2VybWFueS4gZmxvaGVAZGlmZS5kZTwvYXV0aC1hZGRyZXNzPjx0aXRsZXM+PHRpdGxlPkdsdXRh

dGhpb25lIHBlcm94aWRhc2VzIGluIGRpZmZlcmVudCBzdGFnZXMgb2YgY2FyY2lub2dlbmVzaXM8

L3RpdGxlPjxzZWNvbmRhcnktdGl0bGU+QmlvY2hpbSBCaW9waHlzIEFjdGE8L3NlY29uZGFyeS10

aXRsZT48YWx0LXRpdGxlPkJpb2NoaW1pY2EgZXQgYmlvcGh5c2ljYSBhY3RhPC9hbHQtdGl0bGU+

PC90aXRsZXM+PHBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+QmlvY2hpbSBCaW9waHlzIEFjdGE8L2Z1

bGwtdGl0bGU+PGFiYnItMT5CaW9jaGltaWNhIGV0IGJpb3BoeXNpY2EgYWN0YTwvYWJici0xPjwv

cGVyaW9kaWNhbD48YWx0LXBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+QmlvY2hpbSBCaW9waHlzIEFj

dGE8L2Z1bGwtdGl0bGU+PGFiYnItMT5CaW9jaGltaWNhIGV0IGJpb3BoeXNpY2EgYWN0YTwvYWJi

ci0xPjwvYWx0LXBlcmlvZGljYWw+PHBhZ2VzPjE1NTUtNjg8L3BhZ2VzPjx2b2x1bWU+MTc5MDwv

dm9sdW1lPjxudW1iZXI+MTE8L251bWJlcj48ZWRpdGlvbj4yMDA5LzAzLzE4PC9lZGl0aW9uPjxr

ZXl3b3Jkcz48a2V5d29yZD5BbmltYWxzPC9rZXl3b3JkPjxrZXl3b3JkPkNlbGwgVHJhbnNmb3Jt

YXRpb24sIE5lb3BsYXN0aWMvY2hlbWljYWxseSBpbmR1Y2VkLyBnZW5ldGljcy9tZXRhYm9saXNt

L3BhdGhvbG9neTwva2V5d29yZD48a2V5d29yZD5HbHV0YXRoaW9uZSBQZXJveGlkYXNlL2dlbmV0

aWNzL21ldGFib2xpc20vIHBoeXNpb2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+SHVtYW5zPC9rZXl3

b3JkPjxrZXl3b3JkPkh5ZHJvZ2VuIFBlcm94aWRlL2FkdmVyc2UgZWZmZWN0cy9tZXRhYm9saXNt

PC9rZXl3b3JkPjxrZXl3b3JkPkluZmxhbW1hdGlvbi9jb21wbGljYXRpb25zL21ldGFib2xpc208

L2tleXdvcmQ+PGtleXdvcmQ+TWljZTwva2V5d29yZD48a2V5d29yZD5Nb2RlbHMsIEJpb2xvZ2lj

YWw8L2tleXdvcmQ+PGtleXdvcmQ+TmVvcGxhc21zL2NvbXBsaWNhdGlvbnMvZ2VuZXRpY3MvbWV0

YWJvbGlzbTwva2V5d29yZD48L2tleXdvcmRzPjxkYXRlcz48eWVhcj4yMDA5PC95ZWFyPjxwdWIt

ZGF0ZXM+PGRhdGU+Tm92PC9kYXRlPjwvcHViLWRhdGVzPjwvZGF0ZXM+PGlzYm4+MDAwNi0zMDAy

IChQcmludCkmI3hEOzAwMDYtMzAwMiAoTGlua2luZyk8L2lzYm4+PGFjY2Vzc2lvbi1udW0+MTky

ODkxNDk8L2FjY2Vzc2lvbi1udW0+PHVybHM+PC91cmxzPjxlbGVjdHJvbmljLXJlc291cmNlLW51

bT4xMC4xMDE2L2ouYmJhZ2VuLjIwMDkuMDMuMDA2PC9lbGVjdHJvbmljLXJlc291cmNlLW51bT48

cmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPk5MTTwvcmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPjxs

YW5ndWFnZT5lbmc8L2xhbmd1YWdlPjwvcmVjb3JkPjwvQ2l0ZT48Q2l0ZT48QXV0aG9yPlNhZ29u

ZTwvQXV0aG9yPjxZZWFyPjE5ODQ8L1llYXI+PFJlY051bT40NjM8L1JlY051bT48cmVjb3JkPjxy

ZWMtbnVtYmVyPjQ2MzwvcmVjLW51bWJlcj48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIgZGIt

aWQ9Incyd2Z4YWZlNnZhOXo1ZWV2Mmw1NWFhOHN4c2E1OTllZXYycyI+NDYzPC9rZXk+PC9mb3Jl

aWduLWtleXM+PHJlZi10eXBlIG5hbWU9IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBlPjxj

b250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5TYWdvbmUsIEEuIEwuLCBKci48L2F1dGhvcj48

YXV0aG9yPkh1c25leSwgUi48L2F1dGhvcj48YXV0aG9yPkd1dGVyLCBILjwvYXV0aG9yPjxhdXRo

b3I+Q2xhcmssIEwuPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjx0aXRsZXM+PHRp

dGxlPkVmZmVjdCBvZiBjYXRhbGFzZSBvbiB0aGUgcHJvbGlmZXJhdGlvbiBvZiBodW1hbiBseW1w

aG9jeXRlcyB0byBwaG9yYm9sIG15cmlzdGF0ZSBhY2V0YXRlPC90aXRsZT48c2Vjb25kYXJ5LXRp

dGxlPkogSW1tdW5vbDwvc2Vjb25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+Sm91cm5hbCBvZiBpbW11

bm9sb2d5IChCYWx0aW1vcmUsIE1kLiA6IDE5NTApPC9hbHQtdGl0bGU+PC90aXRsZXM+PHBlcmlv

ZGljYWw+PGZ1bGwtdGl0bGU+SiBJbW11bm9sPC9mdWxsLXRpdGxlPjxhYmJyLTE+Sm91cm5hbCBv

ZiBpbW11bm9sb2d5IChCYWx0aW1vcmUsIE1kLiA6IDE5NTApPC9hYmJyLTE+PC9wZXJpb2RpY2Fs

PjxhbHQtcGVyaW9kaWNhbD48ZnVsbC10aXRsZT5KIEltbXVub2w8L2Z1bGwtdGl0bGU+PGFiYnIt

MT5Kb3VybmFsIG9mIGltbXVub2xvZ3kgKEJhbHRpbW9yZSwgTWQuIDogMTk1MCk8L2FiYnItMT48

L2FsdC1wZXJpb2RpY2FsPjxwYWdlcz4xNDg4LTk0PC9wYWdlcz48dm9sdW1lPjEzMzwvdm9sdW1l

PjxudW1iZXI+MzwvbnVtYmVyPjxlZGl0aW9uPjE5ODQvMDkvMDE8L2VkaXRpb24+PGtleXdvcmRz

PjxrZXl3b3JkPkFudGlib2R5LURlcGVuZGVudCBDZWxsIEN5dG90b3hpY2l0eS9kcnVnIGVmZmVj

dHM8L2tleXdvcmQ+PGtleXdvcmQ+Q2F0YWxhc2UvIHBoYXJtYWNvbG9neTwva2V5d29yZD48a2V5

d29yZD5IdW1hbnM8L2tleXdvcmQ+PGtleXdvcmQ+SHlkcm9nZW4gUGVyb3hpZGUvcGhhcm1hY29s

b2d5PC9rZXl3b3JkPjxrZXl3b3JkPktpbmV0aWNzPC9rZXl3b3JkPjxrZXl3b3JkPkx5bXBob2N5

dGUgQWN0aXZhdGlvbi8gZHJ1ZyBlZmZlY3RzPC9rZXl3b3JkPjxrZXl3b3JkPkx5bXBob2N5dGVz

L2ltbXVub2xvZ3kvbWV0YWJvbGlzbS9wYXRob2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+TW9ub2N5

dGVzL3BhdGhvbG9neTwva2V5d29yZD48a2V5d29yZD5PeGlkYXRpb24tUmVkdWN0aW9uPC9rZXl3

b3JkPjxrZXl3b3JkPk94eWdlbi9ibG9vZDwva2V5d29yZD48a2V5d29yZD5QaG9yYm9scy8gcGhh

cm1hY29sb2d5PC9rZXl3b3JkPjxrZXl3b3JkPlRldHJhZGVjYW5veWxwaG9yYm9sIEFjZXRhdGUv

IHBoYXJtYWNvbG9neTwva2V5d29yZD48L2tleXdvcmRzPjxkYXRlcz48eWVhcj4xOTg0PC95ZWFy

PjxwdWItZGF0ZXM+PGRhdGU+U2VwPC9kYXRlPjwvcHViLWRhdGVzPjwvZGF0ZXM+PGlzYm4+MDAy

Mi0xNzY3IChQcmludCkmI3hEOzAwMjItMTc2NyAoTGlua2luZyk8L2lzYm4+PGFjY2Vzc2lvbi1u

dW0+Njc0NzI5NTwvYWNjZXNzaW9uLW51bT48dXJscz48L3VybHM+PHJlbW90ZS1kYXRhYmFzZS1w

cm92aWRlcj5OTE08L3JlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj48bGFuZ3VhZ2U+ZW5nPC9sYW5n

dWFnZT48L3JlY29yZD48L0NpdGU+PC9FbmROb3RlPgB=

ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CcmlnZWxpdXMtRmxvaGU8L0F1dGhvcj48WWVhcj4yMDA5

PC9ZZWFyPjxSZWNOdW0+NDY0PC9SZWNOdW0+PERpc3BsYXlUZXh0Pls3NywgNzhdPC9EaXNwbGF5

VGV4dD48cmVjb3JkPjxyZWMtbnVtYmVyPjQ2NDwvcmVjLW51bWJlcj48Zm9yZWlnbi1rZXlzPjxr

ZXkgYXBwPSJFTiIgZGItaWQ9Incyd2Z4YWZlNnZhOXo1ZWV2Mmw1NWFhOHN4c2E1OTllZXYycyI+

NDY0PC9rZXk+PC9mb3JlaWduLWtleXM+PHJlZi10eXBlIG5hbWU9IkpvdXJuYWwgQXJ0aWNsZSI+

MTc8L3JlZi10eXBlPjxjb250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5CcmlnZWxpdXMtRmxv

aGUsIFIuPC9hdXRob3I+PGF1dGhvcj5LaXBwLCBBLjwvYXV0aG9yPjwvYXV0aG9ycz48L2NvbnRy

aWJ1dG9ycz48YXV0aC1hZGRyZXNzPkRlcGFydG1lbnQgQmlvY2hlbWlzdHJ5IG9mIE1pY3JvbnV0

cmllbnRzLCBHZXJtYW4gSW5zdGl0dXRlIG9mIEh1bWFuIE51dHJpdGlvbiBQb3RzZGFtLVJlaGJy

dWVja2UsIEFydGh1ci1TY2hldW5lcnQtQWxsZWUgMTE0LTExNiwgRC0xNDU1OCBOdXRoZXRhbCwg

R2VybWFueS4gZmxvaGVAZGlmZS5kZTwvYXV0aC1hZGRyZXNzPjx0aXRsZXM+PHRpdGxlPkdsdXRh

dGhpb25lIHBlcm94aWRhc2VzIGluIGRpZmZlcmVudCBzdGFnZXMgb2YgY2FyY2lub2dlbmVzaXM8

L3RpdGxlPjxzZWNvbmRhcnktdGl0bGU+QmlvY2hpbSBCaW9waHlzIEFjdGE8L3NlY29uZGFyeS10

aXRsZT48YWx0LXRpdGxlPkJpb2NoaW1pY2EgZXQgYmlvcGh5c2ljYSBhY3RhPC9hbHQtdGl0bGU+

PC90aXRsZXM+PHBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+QmlvY2hpbSBCaW9waHlzIEFjdGE8L2Z1

bGwtdGl0bGU+PGFiYnItMT5CaW9jaGltaWNhIGV0IGJpb3BoeXNpY2EgYWN0YTwvYWJici0xPjwv

cGVyaW9kaWNhbD48YWx0LXBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+QmlvY2hpbSBCaW9waHlzIEFj

dGE8L2Z1bGwtdGl0bGU+PGFiYnItMT5CaW9jaGltaWNhIGV0IGJpb3BoeXNpY2EgYWN0YTwvYWJi

ci0xPjwvYWx0LXBlcmlvZGljYWw+PHBhZ2VzPjE1NTUtNjg8L3BhZ2VzPjx2b2x1bWU+MTc5MDwv

dm9sdW1lPjxudW1iZXI+MTE8L251bWJlcj48ZWRpdGlvbj4yMDA5LzAzLzE4PC9lZGl0aW9uPjxr

ZXl3b3Jkcz48a2V5d29yZD5BbmltYWxzPC9rZXl3b3JkPjxrZXl3b3JkPkNlbGwgVHJhbnNmb3Jt

YXRpb24sIE5lb3BsYXN0aWMvY2hlbWljYWxseSBpbmR1Y2VkLyBnZW5ldGljcy9tZXRhYm9saXNt

L3BhdGhvbG9neTwva2V5d29yZD48a2V5d29yZD5HbHV0YXRoaW9uZSBQZXJveGlkYXNlL2dlbmV0

aWNzL21ldGFib2xpc20vIHBoeXNpb2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+SHVtYW5zPC9rZXl3

b3JkPjxrZXl3b3JkPkh5ZHJvZ2VuIFBlcm94aWRlL2FkdmVyc2UgZWZmZWN0cy9tZXRhYm9saXNt

PC9rZXl3b3JkPjxrZXl3b3JkPkluZmxhbW1hdGlvbi9jb21wbGljYXRpb25zL21ldGFib2xpc208

L2tleXdvcmQ+PGtleXdvcmQ+TWljZTwva2V5d29yZD48a2V5d29yZD5Nb2RlbHMsIEJpb2xvZ2lj

YWw8L2tleXdvcmQ+PGtleXdvcmQ+TmVvcGxhc21zL2NvbXBsaWNhdGlvbnMvZ2VuZXRpY3MvbWV0

YWJvbGlzbTwva2V5d29yZD48L2tleXdvcmRzPjxkYXRlcz48eWVhcj4yMDA5PC95ZWFyPjxwdWIt

ZGF0ZXM+PGRhdGU+Tm92PC9kYXRlPjwvcHViLWRhdGVzPjwvZGF0ZXM+PGlzYm4+MDAwNi0zMDAy

IChQcmludCkmI3hEOzAwMDYtMzAwMiAoTGlua2luZyk8L2lzYm4+PGFjY2Vzc2lvbi1udW0+MTky

ODkxNDk8L2FjY2Vzc2lvbi1udW0+PHVybHM+PC91cmxzPjxlbGVjdHJvbmljLXJlc291cmNlLW51

bT4xMC4xMDE2L2ouYmJhZ2VuLjIwMDkuMDMuMDA2PC9lbGVjdHJvbmljLXJlc291cmNlLW51bT48

cmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPk5MTTwvcmVtb3RlLWRhdGFiYXNlLXByb3ZpZGVyPjxs

YW5ndWFnZT5lbmc8L2xhbmd1YWdlPjwvcmVjb3JkPjwvQ2l0ZT48Q2l0ZT48QXV0aG9yPlNhZ29u

ZTwvQXV0aG9yPjxZZWFyPjE5ODQ8L1llYXI+PFJlY051bT40NjM8L1JlY051bT48cmVjb3JkPjxy

ZWMtbnVtYmVyPjQ2MzwvcmVjLW51bWJlcj48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIgZGIt

aWQ9Incyd2Z4YWZlNnZhOXo1ZWV2Mmw1NWFhOHN4c2E1OTllZXYycyI+NDYzPC9rZXk+PC9mb3Jl

aWduLWtleXM+PHJlZi10eXBlIG5hbWU9IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBlPjxj

b250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5TYWdvbmUsIEEuIEwuLCBKci48L2F1dGhvcj48

YXV0aG9yPkh1c25leSwgUi48L2F1dGhvcj48YXV0aG9yPkd1dGVyLCBILjwvYXV0aG9yPjxhdXRo

b3I+Q2xhcmssIEwuPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjx0aXRsZXM+PHRp

dGxlPkVmZmVjdCBvZiBjYXRhbGFzZSBvbiB0aGUgcHJvbGlmZXJhdGlvbiBvZiBodW1hbiBseW1w

aG9jeXRlcyB0byBwaG9yYm9sIG15cmlzdGF0ZSBhY2V0YXRlPC90aXRsZT48c2Vjb25kYXJ5LXRp

dGxlPkogSW1tdW5vbDwvc2Vjb25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+Sm91cm5hbCBvZiBpbW11

bm9sb2d5IChCYWx0aW1vcmUsIE1kLiA6IDE5NTApPC9hbHQtdGl0bGU+PC90aXRsZXM+PHBlcmlv

ZGljYWw+PGZ1bGwtdGl0bGU+SiBJbW11bm9sPC9mdWxsLXRpdGxlPjxhYmJyLTE+Sm91cm5hbCBv

ZiBpbW11bm9sb2d5IChCYWx0aW1vcmUsIE1kLiA6IDE5NTApPC9hYmJyLTE+PC9wZXJpb2RpY2Fs

PjxhbHQtcGVyaW9kaWNhbD48ZnVsbC10aXRsZT5KIEltbXVub2w8L2Z1bGwtdGl0bGU+PGFiYnIt

MT5Kb3VybmFsIG9mIGltbXVub2xvZ3kgKEJhbHRpbW9yZSwgTWQuIDogMTk1MCk8L2FiYnItMT48

L2FsdC1wZXJpb2RpY2FsPjxwYWdlcz4xNDg4LTk0PC9wYWdlcz48dm9sdW1lPjEzMzwvdm9sdW1l

PjxudW1iZXI+MzwvbnVtYmVyPjxlZGl0aW9uPjE5ODQvMDkvMDE8L2VkaXRpb24+PGtleXdvcmRz

PjxrZXl3b3JkPkFudGlib2R5LURlcGVuZGVudCBDZWxsIEN5dG90b3hpY2l0eS9kcnVnIGVmZmVj

dHM8L2tleXdvcmQ+PGtleXdvcmQ+Q2F0YWxhc2UvIHBoYXJtYWNvbG9neTwva2V5d29yZD48a2V5

d29yZD5IdW1hbnM8L2tleXdvcmQ+PGtleXdvcmQ+SHlkcm9nZW4gUGVyb3hpZGUvcGhhcm1hY29s

b2d5PC9rZXl3b3JkPjxrZXl3b3JkPktpbmV0aWNzPC9rZXl3b3JkPjxrZXl3b3JkPkx5bXBob2N5

dGUgQWN0aXZhdGlvbi8gZHJ1ZyBlZmZlY3RzPC9rZXl3b3JkPjxrZXl3b3JkPkx5bXBob2N5dGVz

L2ltbXVub2xvZ3kvbWV0YWJvbGlzbS9wYXRob2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+TW9ub2N5

dGVzL3BhdGhvbG9neTwva2V5d29yZD48a2V5d29yZD5PeGlkYXRpb24tUmVkdWN0aW9uPC9rZXl3

b3JkPjxrZXl3b3JkPk94eWdlbi9ibG9vZDwva2V5d29yZD48a2V5d29yZD5QaG9yYm9scy8gcGhh

cm1hY29sb2d5PC9rZXl3b3JkPjxrZXl3b3JkPlRldHJhZGVjYW5veWxwaG9yYm9sIEFjZXRhdGUv

IHBoYXJtYWNvbG9neTwva2V5d29yZD48L2tleXdvcmRzPjxkYXRlcz48eWVhcj4xOTg0PC95ZWFy

PjxwdWItZGF0ZXM+PGRhdGU+U2VwPC9kYXRlPjwvcHViLWRhdGVzPjwvZGF0ZXM+PGlzYm4+MDAy

Mi0xNzY3IChQcmludCkmI3hEOzAwMjItMTc2NyAoTGlua2luZyk8L2lzYm4+PGFjY2Vzc2lvbi1u

dW0+Njc0NzI5NTwvYWNjZXNzaW9uLW51bT48dXJscz48L3VybHM+PHJlbW90ZS1kYXRhYmFzZS1w

cm92aWRlcj5OTE08L3JlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj48bGFuZ3VhZ2U+ZW5nPC9sYW5n

dWFnZT48L3JlY29yZD48L0NpdGU+PC9FbmROb3RlPgB=

ADDIN EN.CITE.DATA [77, 78]

Резюмируя вышесказанное, важно отметить следующее: в клетке постоянно поддерживается баланс между про- и антиоксидантами. Наиболее распространенными прооксидантами являются АФК, к которым относятся: О2•-, Н2О2, НО•, ROO• и др. Основные регуляторы уровня внутриклеточных прооксидантов – антиоксиданты MnСОД, каталаза и GSH. Повышение уровня АФК приводит к гибели клетки, однако в небольших количествах АФК способны индуцировать пролиферативные процессы. Быстро делящиеся опухолевые клетки часто характеризуются повышенным уровнем АФК и пониженной активностью антиоксидантной системы, что возможно является одной из причин их активной пролиферации. Повышение антиоксидантной активности и понижение уровня АФК приводят к замедлению пролиферативных процессов, это открывает возможность контролировать пролиферацию опухолевых с помощью антиоксидантов.

РАЗДЕЛ 1.2.

Редокс-регуляция клеточной пролиферацииДля того чтобы понять, механизм редокс-регуляции пролиферации, необходимо вспомнить - что такое пролиферация. Пролиферация - это процесс увеличения количества клеток, определяющийся соотношением скоростей деления клеток и их гибели. Гибель клеток может происходить как в результате повреждения целостности клетки (некроз), так и путем активации внутриклеточных программ (апоптоз). Деление клетки строго регулируется как внутренними программами, так и внешними факторами (факторы роста, цитокины и др.), воздействующими на внутренние программы. Каждому делению предшествует комплекс последовательных внутриклеточных изменений, т.н. клеточный цикл, основная цель которого – удвоение содержимого клетки и его равномерное распределение между двумя дочерними клетками при делении.

1.2.1. Клеточный цикл и его регуляцияКлеточный цикл представляет собой высокоорганизованную и строго регулируемую последовательность переходов от G1 фазы к S, к G2 и митозу (М). Переход от одной фазы к другой регулируется последовательной экспрессией белков циклинов и активацией циклин-зависимых киназ (cyclin dependent kinase, CDK). CDK представляют собой серин/треоининовые протеинкиназы, которые активируются при соединении с циклинами и запускают события клеточного цикла, путем фосфорилирования соответствующих остатков в белках-мишенях ADDIN EN.CITE <EndNote><Cite><Author>Evans</Author><Year>1983</Year><RecNum>466</RecNum><DisplayText>[79]</DisplayText><record><rec-number>466</rec-number><foreign-keys><key app="EN" db-id="w2wfxafe6va9z5eev2l55aa8sxsa599eev2s">466</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Evans, T.</author><author>Rosenthal, E. T.</author><author>Youngblom, J.</author><author>Distel, D.</author><author>Hunt, T.</author></authors></contributors><titles><title>Cyclin: a protein specified by maternal mRNA in sea urchin eggs that is destroyed at each cleavage division</title><secondary-title>Cell</secondary-title><alt-title>Cell</alt-title></titles><periodical><full-title>Cell</full-title><abbr-1>Cell</abbr-1></periodical><alt-periodical><full-title>Cell</full-title><abbr-1>Cell</abbr-1></alt-periodical><pages>389-96</pages><volume>33</volume><number>2</number><edition>1983/06/01</edition><keywords><keyword>Alkaloids/pharmacology</keyword><keyword>Ammonia/pharmacology</keyword><keyword>Animals</keyword><keyword>Cell Division</keyword><keyword>Colchicine/pharmacology</keyword><keyword>Cytochalasins/metabolism</keyword><keyword>Egg Proteins/analysis/ physiology</keyword><keyword>Female</keyword><keyword>Methionine/metabolism</keyword><keyword>Ovum/metabolism</keyword><keyword>Paclitaxel</keyword><keyword>RNA, Messenger/ metabolism</keyword><keyword>Sea Urchins</keyword><keyword>Zygote/ metabolism</keyword></keywords><dates><year>1983</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>0092-8674 (Print)&#xD;0092-8674 (Linking)</isbn><accession-num>6134587</accession-num><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[79]. На Рис. 1.1. представлены основные циклин/CDK комплексы позвоночных, специфичные для той или иной фазы клеточного цикла. Уровень циклинов меняется по мере прогрессии клеточного цикла, приводя к колебаниям активности CDK (См. Рис. 1.1). Помимо циклинов активность CDK комплексов регулируется с помощью CDK-активирующей киназы (CDK-activating kinase, CAK), ингибиторов CDK (cyclin-dependent kinase inhibitor protein, CKI), а также протеолитическими процессами (убиквитинирование) PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BbGJlcnRzPC9BdXRob3I+PFllYXI+MjAwODwvWWVhcj48

UmVjTnVtPjIyNDwvUmVjTnVtPjxEaXNwbGF5VGV4dD5bODAsIDgxXTwvRGlzcGxheVRleHQ+PHJl

Y29yZD48cmVjLW51bWJlcj4yMjQ8L3JlYy1udW1iZXI+PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0i

RU4iIGRiLWlkPSJ3MndmeGFmZTZ2YTl6NWVldjJsNTVhYThzeHNhNTk5ZWV2MnMiPjIyNDwva2V5

PjwvZm9yZWlnbi1rZXlzPjxyZWYtdHlwZSBuYW1lPSJCb29rIj42PC9yZWYtdHlwZT48Y29udHJp

YnV0b3JzPjxhdXRob3JzPjxhdXRob3I+QWxiZXJ0cywgQi4sIEpvaG5zb24sIEEuLCBMZXdpcywg

Si4sIFJhZmYsIE0uLCBSb2JlcnRzLCBLLiwgV2FsdGVyLCBQLjwvYXV0aG9yPjwvYXV0aG9ycz48

L2NvbnRyaWJ1dG9ycz48dGl0bGVzPjx0aXRsZT5Nb2xlY3VsYXIgQmlvbG9neSBPZiBUaGUgQ2Vs

bC4gRmlmdGggRWRpdGlvbi48L3RpdGxlPjwvdGl0bGVzPjxkYXRlcz48eWVhcj4yMDA4PC95ZWFy

PjwvZGF0ZXM+PHB1Ymxpc2hlcj5OZXcgWW9yazogR2FybGFuZCBTY2llbmNlPC9wdWJsaXNoZXI+

PHVybHM+PC91cmxzPjwvcmVjb3JkPjwvQ2l0ZT48Q2l0ZT48QXV0aG9yPkdyYW5hPC9BdXRob3I+

PFllYXI+MTk5NTwvWWVhcj48UmVjTnVtPjI1OTwvUmVjTnVtPjxyZWNvcmQ+PHJlYy1udW1iZXI+

MjU5PC9yZWMtbnVtYmVyPjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVOIiBkYi1pZD0idzJ3Znhh

ZmU2dmE5ejVlZXYybDU1YWE4c3hzYTU5OWVldjJzIj4yNTk8L2tleT48L2ZvcmVpZ24ta2V5cz48

cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+PGNvbnRyaWJ1dG9y

cz48YXV0aG9ycz48YXV0aG9yPkdyYW5hLCBYLjwvYXV0aG9yPjxhdXRob3I+UmVkZHksIEUuIFAu

PC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjxhdXRoLWFkZHJlc3M+SW5zdGl0dXRl

IGZvciBDYW5jZXIgUmVzZWFyY2ggYW5kIE1vbGVjdWxhciBCaW9sb2d5LCBUZW1wbGUgVW5pdmVy

c2l0eSBTY2hvb2wgb2YgTWVkaWNpbmUsIFBoaWxhZGVscGhpYSwgUEEgMTkxNDAsIFVTQS48L2F1

dGgtYWRkcmVzcz48dGl0bGVzPjx0aXRsZT5DZWxsIGN5Y2xlIGNvbnRyb2wgaW4gbWFtbWFsaWFu

IGNlbGxzOiByb2xlIG9mIGN5Y2xpbnMsIGN5Y2xpbiBkZXBlbmRlbnQga2luYXNlcyAoQ0RLcyks

IGdyb3d0aCBzdXBwcmVzc29yIGdlbmVzIGFuZCBjeWNsaW4tZGVwZW5kZW50IGtpbmFzZSBpbmhp

Yml0b3JzIChDS0lzKTwvdGl0bGU+PHNlY29uZGFyeS10aXRsZT5PbmNvZ2VuZTwvc2Vjb25kYXJ5

LXRpdGxlPjxhbHQtdGl0bGU+T25jb2dlbmU8L2FsdC10aXRsZT48L3RpdGxlcz48cGVyaW9kaWNh

bD48ZnVsbC10aXRsZT5PbmNvZ2VuZTwvZnVsbC10aXRsZT48YWJici0xPk9uY29nZW5lPC9hYmJy

LTE+PC9wZXJpb2RpY2FsPjxhbHQtcGVyaW9kaWNhbD48ZnVsbC10aXRsZT5PbmNvZ2VuZTwvZnVs

bC10aXRsZT48YWJici0xPk9uY29nZW5lPC9hYmJyLTE+PC9hbHQtcGVyaW9kaWNhbD48cGFnZXM+

MjExLTk8L3BhZ2VzPjx2b2x1bWU+MTE8L3ZvbHVtZT48bnVtYmVyPjI8L251bWJlcj48ZWRpdGlv

bj4xOTk1LzA3LzIwPC9lZGl0aW9uPjxrZXl3b3Jkcz48a2V5d29yZD5BbmltYWxzPC9rZXl3b3Jk

PjxrZXl3b3JkPkNlbGwgQ3ljbGUvIHBoeXNpb2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+Q3ljbGlu

LURlcGVuZGVudCBLaW5hc2VzLyBhbnRhZ29uaXN0cyAmYW1wOyBpbmhpYml0b3JzLyBwaHlzaW9s

b2d5PC9rZXl3b3JkPjxrZXl3b3JkPkN5Y2xpbnMvIHBoeXNpb2xvZ3k8L2tleXdvcmQ+PGtleXdv

cmQ+RW56eW1lIEluaGliaXRvcnMvIHBoYXJtYWNvbG9neTwva2V5d29yZD48a2V5d29yZD5HZW5l

cywgVHVtb3IgU3VwcHJlc3Nvcjwva2V5d29yZD48a2V5d29yZD5IdW1hbnM8L2tleXdvcmQ+PC9r

ZXl3b3Jkcz48ZGF0ZXM+PHllYXI+MTk5NTwveWVhcj48cHViLWRhdGVzPjxkYXRlPkp1bCAyMDwv

ZGF0ZT48L3B1Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjA5NTAtOTIzMiAoUHJpbnQpJiN4RDswOTUw

LTkyMzIgKExpbmtpbmcpPC9pc2JuPjxhY2Nlc3Npb24tbnVtPjc2MjQxMzg8L2FjY2Vzc2lvbi1u

dW0+PHVybHM+PC91cmxzPjxyZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+TkxNPC9yZW1vdGUtZGF0

YWJhc2UtcHJvdmlkZXI+PGxhbmd1YWdlPmVuZzwvbGFuZ3VhZ2U+PC9yZWNvcmQ+PC9DaXRlPjwv

RW5kTm90ZT4A

ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BbGJlcnRzPC9BdXRob3I+PFllYXI+MjAwODwvWWVhcj48

UmVjTnVtPjIyNDwvUmVjTnVtPjxEaXNwbGF5VGV4dD5bODAsIDgxXTwvRGlzcGxheVRleHQ+PHJl

Y29yZD48cmVjLW51bWJlcj4yMjQ8L3JlYy1udW1iZXI+PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0i

RU4iIGRiLWlkPSJ3MndmeGFmZTZ2YTl6NWVldjJsNTVhYThzeHNhNTk5ZWV2MnMiPjIyNDwva2V5

PjwvZm9yZWlnbi1rZXlzPjxyZWYtdHlwZSBuYW1lPSJCb29rIj42PC9yZWYtdHlwZT48Y29udHJp

YnV0b3JzPjxhdXRob3JzPjxhdXRob3I+QWxiZXJ0cywgQi4sIEpvaG5zb24sIEEuLCBMZXdpcywg

Si4sIFJhZmYsIE0uLCBSb2JlcnRzLCBLLiwgV2FsdGVyLCBQLjwvYXV0aG9yPjwvYXV0aG9ycz48

L2NvbnRyaWJ1dG9ycz48dGl0bGVzPjx0aXRsZT5Nb2xlY3VsYXIgQmlvbG9neSBPZiBUaGUgQ2Vs

bC4gRmlmdGggRWRpdGlvbi48L3RpdGxlPjwvdGl0bGVzPjxkYXRlcz48eWVhcj4yMDA4PC95ZWFy

PjwvZGF0ZXM+PHB1Ymxpc2hlcj5OZXcgWW9yazogR2FybGFuZCBTY2llbmNlPC9wdWJsaXNoZXI+

PHVybHM+PC91cmxzPjwvcmVjb3JkPjwvQ2l0ZT48Q2l0ZT48QXV0aG9yPkdyYW5hPC9BdXRob3I+

PFllYXI+MTk5NTwvWWVhcj48UmVjTnVtPjI1OTwvUmVjTnVtPjxyZWNvcmQ+PHJlYy1udW1iZXI+

MjU5PC9yZWMtbnVtYmVyPjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVOIiBkYi1pZD0idzJ3Znhh

ZmU2dmE5ejVlZXYybDU1YWE4c3hzYTU5OWVldjJzIj4yNTk8L2tleT48L2ZvcmVpZ24ta2V5cz48

cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+PGNvbnRyaWJ1dG9y

cz48YXV0aG9ycz48YXV0aG9yPkdyYW5hLCBYLjwvYXV0aG9yPjxhdXRob3I+UmVkZHksIEUuIFAu

PC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjxhdXRoLWFkZHJlc3M+SW5zdGl0dXRl

IGZvciBDYW5jZXIgUmVzZWFyY2ggYW5kIE1vbGVjdWxhciBCaW9sb2d5LCBUZW1wbGUgVW5pdmVy

c2l0eSBTY2hvb2wgb2YgTWVkaWNpbmUsIFBoaWxhZGVscGhpYSwgUEEgMTkxNDAsIFVTQS48L2F1

dGgtYWRkcmVzcz48dGl0bGVzPjx0aXRsZT5DZWxsIGN5Y2xlIGNvbnRyb2wgaW4gbWFtbWFsaWFu

IGNlbGxzOiByb2xlIG9mIGN5Y2xpbnMsIGN5Y2xpbiBkZXBlbmRlbnQga2luYXNlcyAoQ0RLcyks

IGdyb3d0aCBzdXBwcmVzc29yIGdlbmVzIGFuZCBjeWNsaW4tZGVwZW5kZW50IGtpbmFzZSBpbmhp

Yml0b3JzIChDS0lzKTwvdGl0bGU+PHNlY29uZGFyeS10aXRsZT5PbmNvZ2VuZTwvc2Vjb25kYXJ5

LXRpdGxlPjxhbHQtdGl0bGU+T25jb2dlbmU8L2FsdC10aXRsZT48L3RpdGxlcz48cGVyaW9kaWNh

bD48ZnVsbC10aXRsZT5PbmNvZ2VuZTwvZnVsbC10aXRsZT48YWJici0xPk9uY29nZW5lPC9hYmJy

LTE+PC9wZXJpb2RpY2FsPjxhbHQtcGVyaW9kaWNhbD48ZnVsbC10aXRsZT5PbmNvZ2VuZTwvZnVs

bC10aXRsZT48YWJici0xPk9uY29nZW5lPC9hYmJyLTE+PC9hbHQtcGVyaW9kaWNhbD48cGFnZXM+

MjExLTk8L3BhZ2VzPjx2b2x1bWU+MTE8L3ZvbHVtZT48bnVtYmVyPjI8L251bWJlcj48ZWRpdGlv

bj4xOTk1LzA3LzIwPC9lZGl0aW9uPjxrZXl3b3Jkcz48a2V5d29yZD5BbmltYWxzPC9rZXl3b3Jk

PjxrZXl3b3JkPkNlbGwgQ3ljbGUvIHBoeXNpb2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+Q3ljbGlu

LURlcGVuZGVudCBLaW5hc2VzLyBhbnRhZ29uaXN0cyAmYW1wOyBpbmhpYml0b3JzLyBwaHlzaW9s

b2d5PC9rZXl3b3JkPjxrZXl3b3JkPkN5Y2xpbnMvIHBoeXNpb2xvZ3k8L2tleXdvcmQ+PGtleXdv

cmQ+RW56eW1lIEluaGliaXRvcnMvIHBoYXJtYWNvbG9neTwva2V5d29yZD48a2V5d29yZD5HZW5l

cywgVHVtb3IgU3VwcHJlc3Nvcjwva2V5d29yZD48a2V5d29yZD5IdW1hbnM8L2tleXdvcmQ+PC9r

ZXl3b3Jkcz48ZGF0ZXM+PHllYXI+MTk5NTwveWVhcj48cHViLWRhdGVzPjxkYXRlPkp1bCAyMDwv

ZGF0ZT48L3B1Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjA5NTAtOTIzMiAoUHJpbnQpJiN4RDswOTUw

LTkyMzIgKExpbmtpbmcpPC9pc2JuPjxhY2Nlc3Npb24tbnVtPjc2MjQxMzg8L2FjY2Vzc2lvbi1u

dW0+PHVybHM+PC91cmxzPjxyZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+TkxNPC9yZW1vdGUtZGF0

YWJhc2UtcHJvdmlkZXI+PGxhbmd1YWdlPmVuZzwvbGFuZ3VhZ2U+PC9yZWNvcmQ+PC9DaXRlPjwv

RW5kTm90ZT4A

ADDIN EN.CITE.DATA [80, 81]. Для полной активации комплекса циклин/CDK необходимо фосфорилирование CDK по Thr161 (CDK1), Thr160 (CDK2) или Thr172/177 (CDK4/6), которое осуществляется в ядре с помощью CAK PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5EdWNvbW11bjwvQXV0aG9yPjxZZWFyPjE5OTE8L1llYXI+

PFJlY051bT40OTQ8L1JlY051bT48RGlzcGxheVRleHQ+WzgzLTg1XTwvRGlzcGxheVRleHQ+PHJl

Y29yZD48cmVjLW51bWJlcj40OTQ8L3JlYy1udW1iZXI+PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0i

RU4iIGRiLWlkPSJ3MndmeGFmZTZ2YTl6NWVldjJsNTVhYThzeHNhNTk5ZWV2MnMiPjQ5NDwva2V5

PjwvZm9yZWlnbi1rZXlzPjxyZWYtdHlwZSBuYW1lPSJKb3VybmFsIEFydGljbGUiPjE3PC9yZWYt

dHlwZT48Y29udHJpYnV0b3JzPjxhdXRob3JzPjxhdXRob3I+RHVjb21tdW4sIEIuPC9hdXRob3I+

PGF1dGhvcj5CcmFtYmlsbGEsIFAuPC9hdXRob3I+PGF1dGhvcj5GZWxpeCwgTS4gQS48L2F1dGhv

cj48YXV0aG9yPkZyYW56YSwgQi4gUi4sIEpyLjwvYXV0aG9yPjxhdXRob3I+S2Fyc2VudGksIEUu

PC9hdXRob3I+PGF1dGhvcj5EcmFldHRhLCBHLjwvYXV0aG9yPjwvYXV0aG9ycz48L2NvbnRyaWJ1

dG9ycz48YXV0aC1hZGRyZXNzPkRpZmZlcmVudGlhdGlvbiBQcm9ncmFtLCBFdXJvcGVhbiBNb2xl

Y3VsYXIgQmlvbG9neSBMYWJvcmF0b3J5LCBIZWlkZWxiZXJnLCBGUkcuPC9hdXRoLWFkZHJlc3M+

PHRpdGxlcz48dGl0bGU+Y2RjMiBwaG9zcGhvcnlsYXRpb24gaXMgcmVxdWlyZWQgZm9yIGl0cyBp

bnRlcmFjdGlvbiB3aXRoIGN5Y2xpbjwvdGl0bGU+PHNlY29uZGFyeS10aXRsZT5FTUJPIEo8L3Nl

Y29uZGFyeS10aXRsZT48YWx0LXRpdGxlPlRoZSBFTUJPIGpvdXJuYWw8L2FsdC10aXRsZT48L3Rp

dGxlcz48cGVyaW9kaWNhbD48ZnVsbC10aXRsZT5FTUJPIEo8L2Z1bGwtdGl0bGU+PGFiYnItMT5U

aGUgRU1CTyBqb3VybmFsPC9hYmJyLTE+PC9wZXJpb2RpY2FsPjxhbHQtcGVyaW9kaWNhbD48ZnVs

bC10aXRsZT5FTUJPIEo8L2Z1bGwtdGl0bGU+PGFiYnItMT5UaGUgRU1CTyBqb3VybmFsPC9hYmJy

LTE+PC9hbHQtcGVyaW9kaWNhbD48cGFnZXM+MzMxMS05PC9wYWdlcz48dm9sdW1lPjEwPC92b2x1

bWU+PG51bWJlcj4xMTwvbnVtYmVyPjxlZGl0aW9uPjE5OTEvMTEvMTE8L2VkaXRpb24+PGtleXdv

cmRzPjxrZXl3b3JkPkFtaW5vIEFjaWQgU2VxdWVuY2U8L2tleXdvcmQ+PGtleXdvcmQ+QW5pbWFs

czwva2V5d29yZD48a2V5d29yZD5DREMyIFByb3RlaW4gS2luYXNlL2dlbmV0aWNzLyBtZXRhYm9s

aXNtPC9rZXl3b3JkPjxrZXl3b3JkPkN5Y2xpbnMvIG1ldGFib2xpc208L2tleXdvcmQ+PGtleXdv

cmQ+RWxlY3Ryb3Bob3Jlc2lzLCBHZWwsIFR3by1EaW1lbnNpb25hbDwva2V5d29yZD48a2V5d29y

ZD5FbGVjdHJvcGhvcmVzaXMsIFBvbHlhY3J5bGFtaWRlIEdlbDwva2V5d29yZD48a2V5d29yZD5H

ZW5lIEV4cHJlc3Npb248L2tleXdvcmQ+PGtleXdvcmQ+R2VuZXMsIEZ1bmdhbDwva2V5d29yZD48

a2V5d29yZD5IdW1hbnM8L2tleXdvcmQ+PGtleXdvcmQ+TW9sZWN1bGFyIFNlcXVlbmNlIERhdGE8

L2tleXdvcmQ+PGtleXdvcmQ+TXV0YWdlbmVzaXMsIFNpdGUtRGlyZWN0ZWQ8L2tleXdvcmQ+PGtl

eXdvcmQ+UGhvc3Bob3J5bGF0aW9uPC9rZXl3b3JkPjxrZXl3b3JkPlByb3RlaW4gQmlvc3ludGhl

c2lzPC9rZXl3b3JkPjxrZXl3b3JkPlNjaGl6b3NhY2NoYXJvbXljZXMvZ2VuZXRpY3M8L2tleXdv

cmQ+PGtleXdvcmQ+VGhyZW9uaW5lL2dlbmV0aWNzPC9rZXl3b3JkPjxrZXl3b3JkPlRyYW5zY3Jp

cHRpb24sIEdlbmV0aWM8L2tleXdvcmQ+PGtleXdvcmQ+WGVub3B1czwva2V5d29yZD48L2tleXdv

cmRzPjxkYXRlcz48eWVhcj4xOTkxPC95ZWFyPjxwdWItZGF0ZXM+PGRhdGU+Tm92PC9kYXRlPjwv

cHViLWRhdGVzPjwvZGF0ZXM+PGlzYm4+MDI2MS00MTg5IChQcmludCkmI3hEOzAyNjEtNDE4OSAo

TGlua2luZyk8L2lzYm4+PGFjY2Vzc2lvbi1udW0+MTgzMzE4NTwvYWNjZXNzaW9uLW51bT48dXJs

cz48L3VybHM+PGN1c3RvbTI+UE1DNDUzMDU3PC9jdXN0b20yPjxyZW1vdGUtZGF0YWJhc2UtcHJv

dmlkZXI+TkxNPC9yZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+PGxhbmd1YWdlPmVuZzwvbGFuZ3Vh

Z2U+PC9yZWNvcmQ+PC9DaXRlPjxDaXRlPjxBdXRob3I+SmVmZnJleTwvQXV0aG9yPjxZZWFyPjE5

OTU8L1llYXI+PFJlY051bT40OTM8L1JlY051bT48cmVjb3JkPjxyZWMtbnVtYmVyPjQ5MzwvcmVj

LW51bWJlcj48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIgZGItaWQ9Incyd2Z4YWZlNnZhOXo1

ZWV2Mmw1NWFhOHN4c2E1OTllZXYycyI+NDkzPC9rZXk+PC9mb3JlaWduLWtleXM+PHJlZi10eXBl

IG5hbWU9IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBlPjxjb250cmlidXRvcnM+PGF1dGhv

cnM+PGF1dGhvcj5KZWZmcmV5LCBQLiBELjwvYXV0aG9yPjxhdXRob3I+UnVzc28sIEEuIEEuPC9h

dXRob3I+PGF1dGhvcj5Qb2x5YWssIEsuPC9hdXRob3I+PGF1dGhvcj5HaWJicywgRS48L2F1dGhv

cj48YXV0aG9yPkh1cndpdHosIEouPC9hdXRob3I+PGF1dGhvcj5NYXNzYWd1ZSwgSi48L2F1dGhv

cj48YXV0aG9yPlBhdmxldGljaCwgTi4gUC48L2F1dGhvcj48L2F1dGhvcnM+PC9jb250cmlidXRv

cnM+PGF1dGgtYWRkcmVzcz5DZWxsdWxhciBCaW9jaGVtaXN0cnkgYW5kIEJpb3BoeXNpY3MgUHJv

Z3JhbSwgTWVtb3JpYWwgU2xvYW4tS2V0dGVyaW5nIENhbmNlciBDZW50ZXIsIE5ldyBZb3JrLCBO

ZXcgWW9yayAxMDAyMSwgVVNBLjwvYXV0aC1hZGRyZXNzPjx0aXRsZXM+PHRpdGxlPk1lY2hhbmlz

bSBvZiBDREsgYWN0aXZhdGlvbiByZXZlYWxlZCBieSB0aGUgc3RydWN0dXJlIG9mIGEgY3ljbGlu

QS1DREsyIGNvbXBsZXg8L3RpdGxlPjxzZWNvbmRhcnktdGl0bGU+TmF0dXJlPC9zZWNvbmRhcnkt

dGl0bGU+PGFsdC10aXRsZT5OYXR1cmU8L2FsdC10aXRsZT48L3RpdGxlcz48cGVyaW9kaWNhbD48

ZnVsbC10aXRsZT5OYXR1cmU8L2Z1bGwtdGl0bGU+PGFiYnItMT5OYXR1cmU8L2FiYnItMT48L3Bl

cmlvZGljYWw+PGFsdC1wZXJpb2RpY2FsPjxmdWxsLXRpdGxlPk5hdHVyZTwvZnVsbC10aXRsZT48

YWJici0xPk5hdHVyZTwvYWJici0xPjwvYWx0LXBlcmlvZGljYWw+PHBhZ2VzPjMxMy0yMDwvcGFn

ZXM+PHZvbHVtZT4zNzY8L3ZvbHVtZT48bnVtYmVyPjY1Mzg8L251bWJlcj48ZWRpdGlvbj4xOTk1

LzA3LzI3PC9lZGl0aW9uPjxrZXl3b3Jkcz48a2V5d29yZD5BZGVub3NpbmUgVHJpcGhvc3BoYXRl

L2NoZW1pc3RyeS9tZXRhYm9saXNtPC9rZXl3b3JkPjxrZXl3b3JkPkFsbG9zdGVyaWMgUmVndWxh

dGlvbjwva2V5d29yZD48a2V5d29yZD5BbWlubyBBY2lkIFNlcXVlbmNlPC9rZXl3b3JkPjxrZXl3

b3JkPkJpbmRpbmcgU2l0ZXM8L2tleXdvcmQ+PGtleXdvcmQ+Q0RDMi1DREMyOCBLaW5hc2VzPC9r

ZXl3b3JkPjxrZXl3b3JkPkNvbXB1dGVyIEdyYXBoaWNzPC9rZXl3b3JkPjxrZXl3b3JkPkNyeXN0

YWxsb2dyYXBoeSwgWC1SYXk8L2tleXdvcmQ+PGtleXdvcmQ+Q3ljbGljIEFNUC1EZXBlbmRlbnQg

UHJvdGVpbiBLaW5hc2VzL2NoZW1pc3RyeTwva2V5d29yZD48a2V5d29yZD5DeWNsaW4tRGVwZW5k

ZW50IEtpbmFzZSAyPC9rZXl3b3JkPjxrZXl3b3JkPkN5Y2xpbi1EZXBlbmRlbnQgS2luYXNlcy8g

Y2hlbWlzdHJ5L21ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+Q3ljbGlucy8gY2hlbWlzdHJ5

L21ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+RW56eW1lIEFjdGl2YXRpb248L2tleXdvcmQ+

PGtleXdvcmQ+RXNjaGVyaWNoaWEgY29saTwva2V5d29yZD48a2V5d29yZD5IdW1hbnM8L2tleXdv

cmQ+PGtleXdvcmQ+TW9sZWN1bGFyIFNlcXVlbmNlIERhdGE8L2tleXdvcmQ+PGtleXdvcmQ+UGhv

c3Bob3J5bGF0aW9uPC9rZXl3b3JkPjxrZXl3b3JkPlByb3RlaW4gQmluZGluZzwva2V5d29yZD48

a2V5d29yZD5Qcm90ZWluIENvbmZvcm1hdGlvbjwva2V5d29yZD48a2V5d29yZD5Qcm90ZWluIEZv

bGRpbmc8L2tleXdvcmQ+PGtleXdvcmQ+UHJvdGVpbi1TZXJpbmUtVGhyZW9uaW5lIEtpbmFzZXMv

IGNoZW1pc3RyeS9tZXRhYm9saXNtPC9rZXl3b3JkPjxrZXl3b3JkPlJlY29tYmluYW50IFByb3Rl

aW5zL2NoZW1pc3RyeTwva2V5d29yZD48a2V5d29yZD5UaHJlb25pbmUvY2hlbWlzdHJ5PC9rZXl3

b3JkPjwva2V5d29yZHM+PGRhdGVzPjx5ZWFyPjE5OTU8L3llYXI+PHB1Yi1kYXRlcz48ZGF0ZT5K

dWwgMjc8L2RhdGU+PC9wdWItZGF0ZXM+PC9kYXRlcz48aXNibj4wMDI4LTA4MzYgKFByaW50KSYj

eEQ7MDAyOC0wODM2IChMaW5raW5nKTwvaXNibj48YWNjZXNzaW9uLW51bT43NjMwMzk3PC9hY2Nl

c3Npb24tbnVtPjx1cmxzPjwvdXJscz48ZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+MTAuMTAzOC8z

NzYzMTNhMDwvZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+PHJlbW90ZS1kYXRhYmFzZS1wcm92aWRl

cj5OTE08L3JlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj48bGFuZ3VhZ2U+ZW5nPC9sYW5ndWFnZT48

L3JlY29yZD48L0NpdGU+PENpdGU+PEF1dGhvcj5EaWVobDwvQXV0aG9yPjxZZWFyPjE5OTc8L1ll

YXI+PFJlY051bT40OTI8L1JlY051bT48cmVjb3JkPjxyZWMtbnVtYmVyPjQ5MjwvcmVjLW51bWJl

cj48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIgZGItaWQ9Incyd2Z4YWZlNnZhOXo1ZWV2Mmw1

NWFhOHN4c2E1OTllZXYycyI+NDkyPC9rZXk+PC9mb3JlaWduLWtleXM+PHJlZi10eXBlIG5hbWU9

IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBlPjxjb250cmlidXRvcnM+PGF1dGhvcnM+PGF1

dGhvcj5EaWVobCwgSi4gQS48L2F1dGhvcj48YXV0aG9yPlNoZXJyLCBDLiBKLjwvYXV0aG9yPjwv

YXV0aG9ycz48L2NvbnRyaWJ1dG9ycz48YXV0aC1hZGRyZXNzPkhvd2FyZCBIdWdoZXMgTWVkaWNh

bCBJbnN0aXR1dGUsIERlcGFydG1lbnQgb2YgVHVtb3IgQ2VsbCBCaW9sb2d5LCBTdC4gSnVkZSBD

aGlsZHJlbiZhcG9zO3MgUmVzZWFyY2ggSG9zcGl0YWwsIE1lbXBoaXMsIFRlbm5lc3NlZSAzODEw

NSwgVVNBLjwvYXV0aC1hZGRyZXNzPjx0aXRsZXM+PHRpdGxlPkEgZG9taW5hbnQtbmVnYXRpdmUg

Y3ljbGluIEQxIG11dGFudCBwcmV2ZW50cyBudWNsZWFyIGltcG9ydCBvZiBjeWNsaW4tZGVwZW5k

ZW50IGtpbmFzZSA0IChDREs0KSBhbmQgaXRzIHBob3NwaG9yeWxhdGlvbiBieSBDREstYWN0aXZh

dGluZyBraW5hc2U8L3RpdGxlPjxzZWNvbmRhcnktdGl0bGU+TW9sIENlbGwgQmlvbDwvc2Vjb25k

YXJ5LXRpdGxlPjxhbHQtdGl0bGU+TW9sZWN1bGFyIGFuZCBjZWxsdWxhciBiaW9sb2d5PC9hbHQt

dGl0bGU+PC90aXRsZXM+PHBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+TW9sIENlbGwgQmlvbDwvZnVs

bC10aXRsZT48YWJici0xPk1vbGVjdWxhciBhbmQgY2VsbHVsYXIgYmlvbG9neTwvYWJici0xPjwv

cGVyaW9kaWNhbD48YWx0LXBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+TW9sIENlbGwgQmlvbDwvZnVs

bC10aXRsZT48YWJici0xPk1vbGVjdWxhciBhbmQgY2VsbHVsYXIgYmlvbG9neTwvYWJici0xPjwv

YWx0LXBlcmlvZGljYWw+PHBhZ2VzPjczNjItNzQ8L3BhZ2VzPjx2b2x1bWU+MTc8L3ZvbHVtZT48

bnVtYmVyPjEyPC9udW1iZXI+PGVkaXRpb24+MTk5Ny8xMi8zMTwvZWRpdGlvbj48a2V5d29yZHM+

PGtleXdvcmQ+M1QzIENlbGxzPC9rZXl3b3JkPjxrZXl3b3JkPkFuaW1hbHM8L2tleXdvcmQ+PGtl

eXdvcmQ+QmFzZSBTZXF1ZW5jZTwva2V5d29yZD48a2V5d29yZD5CaW9sb2dpY2FsIFRyYW5zcG9y

dCwgQWN0aXZlL2dlbmV0aWNzPC9rZXl3b3JkPjxrZXl3b3JkPkNlbGwgQ3ljbGUvZ2VuZXRpY3Mv

cGh5c2lvbG9neTwva2V5d29yZD48a2V5d29yZD5DZWxsIE51Y2xldXMvbWV0YWJvbGlzbTwva2V5

d29yZD48a2V5d29yZD5DeWNsaW4gRDEvY2hlbWlzdHJ5LyBnZW5ldGljcy8gbWV0YWJvbGlzbTwv

a2V5d29yZD48a2V5d29yZD5DeWNsaW4tRGVwZW5kZW50IEtpbmFzZSA0PC9rZXl3b3JkPjxrZXl3

b3JkPkN5Y2xpbi1EZXBlbmRlbnQgS2luYXNlcy9jaGVtaXN0cnkvIG1ldGFib2xpc208L2tleXdv

cmQ+PGtleXdvcmQ+Q3l0b3BsYXNtL21ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+RE5BIFBy

aW1lcnMvZ2VuZXRpY3M8L2tleXdvcmQ+PGtleXdvcmQ+TWFjcm9tb2xlY3VsYXIgU3Vic3RhbmNl

czwva2V5d29yZD48a2V5d29yZD5NaWNlPC9rZXl3b3JkPjxrZXl3b3JkPk11dGF0aW9uPC9rZXl3

b3JkPjxrZXl3b3JkPlBob3NwaG9yeWxhdGlvbjwva2V5d29yZD48a2V5d29yZD5Qb2x5bWVyYXNl

IENoYWluIFJlYWN0aW9uPC9rZXl3b3JkPjxrZXl3b3JkPlByb3RlaW4gQ29uZm9ybWF0aW9uPC9r

ZXl3b3JkPjxrZXl3b3JkPlByb3RlaW4tU2VyaW5lLVRocmVvbmluZSBLaW5hc2VzLyBtZXRhYm9s

aXNtPC9rZXl3b3JkPjxrZXl3b3JkPlByb3RvLU9uY29nZW5lIFByb3RlaW5zPC9rZXl3b3JkPjxr

ZXl3b3JkPlRyYW5zZmVjdGlvbjwva2V5d29yZD48L2tleXdvcmRzPjxkYXRlcz48eWVhcj4xOTk3

PC95ZWFyPjxwdWItZGF0ZXM+PGRhdGU+RGVjPC9kYXRlPjwvcHViLWRhdGVzPjwvZGF0ZXM+PGlz

Ym4+MDI3MC03MzA2IChQcmludCkmI3hEOzAyNzAtNzMwNiAoTGlua2luZyk8L2lzYm4+PGFjY2Vz

c2lvbi1udW0+OTM3Mjk2NzwvYWNjZXNzaW9uLW51bT48dXJscz48L3VybHM+PGN1c3RvbTI+UE1D

MjMyNTkyPC9jdXN0b20yPjxyZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+TkxNPC9yZW1vdGUtZGF0

YWJhc2UtcHJvdmlkZXI+PGxhbmd1YWdlPmVuZzwvbGFuZ3VhZ2U+PC9yZWNvcmQ+PC9DaXRlPjwv

RW5kTm90ZT5=

ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5EdWNvbW11bjwvQXV0aG9yPjxZZWFyPjE5OTE8L1llYXI+

PFJlY051bT40OTQ8L1JlY051bT48RGlzcGxheVRleHQ+WzgzLTg1XTwvRGlzcGxheVRleHQ+PHJl

Y29yZD48cmVjLW51bWJlcj40OTQ8L3JlYy1udW1iZXI+PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0i

RU4iIGRiLWlkPSJ3MndmeGFmZTZ2YTl6NWVldjJsNTVhYThzeHNhNTk5ZWV2MnMiPjQ5NDwva2V5

PjwvZm9yZWlnbi1rZXlzPjxyZWYtdHlwZSBuYW1lPSJKb3VybmFsIEFydGljbGUiPjE3PC9yZWYt

dHlwZT48Y29udHJpYnV0b3JzPjxhdXRob3JzPjxhdXRob3I+RHVjb21tdW4sIEIuPC9hdXRob3I+

PGF1dGhvcj5CcmFtYmlsbGEsIFAuPC9hdXRob3I+PGF1dGhvcj5GZWxpeCwgTS4gQS48L2F1dGhv

cj48YXV0aG9yPkZyYW56YSwgQi4gUi4sIEpyLjwvYXV0aG9yPjxhdXRob3I+S2Fyc2VudGksIEUu

PC9hdXRob3I+PGF1dGhvcj5EcmFldHRhLCBHLjwvYXV0aG9yPjwvYXV0aG9ycz48L2NvbnRyaWJ1

dG9ycz48YXV0aC1hZGRyZXNzPkRpZmZlcmVudGlhdGlvbiBQcm9ncmFtLCBFdXJvcGVhbiBNb2xl

Y3VsYXIgQmlvbG9neSBMYWJvcmF0b3J5LCBIZWlkZWxiZXJnLCBGUkcuPC9hdXRoLWFkZHJlc3M+

PHRpdGxlcz48dGl0bGU+Y2RjMiBwaG9zcGhvcnlsYXRpb24gaXMgcmVxdWlyZWQgZm9yIGl0cyBp

bnRlcmFjdGlvbiB3aXRoIGN5Y2xpbjwvdGl0bGU+PHNlY29uZGFyeS10aXRsZT5FTUJPIEo8L3Nl

Y29uZGFyeS10aXRsZT48YWx0LXRpdGxlPlRoZSBFTUJPIGpvdXJuYWw8L2FsdC10aXRsZT48L3Rp

dGxlcz48cGVyaW9kaWNhbD48ZnVsbC10aXRsZT5FTUJPIEo8L2Z1bGwtdGl0bGU+PGFiYnItMT5U

aGUgRU1CTyBqb3VybmFsPC9hYmJyLTE+PC9wZXJpb2RpY2FsPjxhbHQtcGVyaW9kaWNhbD48ZnVs

bC10aXRsZT5FTUJPIEo8L2Z1bGwtdGl0bGU+PGFiYnItMT5UaGUgRU1CTyBqb3VybmFsPC9hYmJy

LTE+PC9hbHQtcGVyaW9kaWNhbD48cGFnZXM+MzMxMS05PC9wYWdlcz48dm9sdW1lPjEwPC92b2x1

bWU+PG51bWJlcj4xMTwvbnVtYmVyPjxlZGl0aW9uPjE5OTEvMTEvMTE8L2VkaXRpb24+PGtleXdv

cmRzPjxrZXl3b3JkPkFtaW5vIEFjaWQgU2VxdWVuY2U8L2tleXdvcmQ+PGtleXdvcmQ+QW5pbWFs

czwva2V5d29yZD48a2V5d29yZD5DREMyIFByb3RlaW4gS2luYXNlL2dlbmV0aWNzLyBtZXRhYm9s

aXNtPC9rZXl3b3JkPjxrZXl3b3JkPkN5Y2xpbnMvIG1ldGFib2xpc208L2tleXdvcmQ+PGtleXdv

cmQ+RWxlY3Ryb3Bob3Jlc2lzLCBHZWwsIFR3by1EaW1lbnNpb25hbDwva2V5d29yZD48a2V5d29y

ZD5FbGVjdHJvcGhvcmVzaXMsIFBvbHlhY3J5bGFtaWRlIEdlbDwva2V5d29yZD48a2V5d29yZD5H

ZW5lIEV4cHJlc3Npb248L2tleXdvcmQ+PGtleXdvcmQ+R2VuZXMsIEZ1bmdhbDwva2V5d29yZD48

a2V5d29yZD5IdW1hbnM8L2tleXdvcmQ+PGtleXdvcmQ+TW9sZWN1bGFyIFNlcXVlbmNlIERhdGE8

L2tleXdvcmQ+PGtleXdvcmQ+TXV0YWdlbmVzaXMsIFNpdGUtRGlyZWN0ZWQ8L2tleXdvcmQ+PGtl

eXdvcmQ+UGhvc3Bob3J5bGF0aW9uPC9rZXl3b3JkPjxrZXl3b3JkPlByb3RlaW4gQmlvc3ludGhl

c2lzPC9rZXl3b3JkPjxrZXl3b3JkPlNjaGl6b3NhY2NoYXJvbXljZXMvZ2VuZXRpY3M8L2tleXdv

cmQ+PGtleXdvcmQ+VGhyZW9uaW5lL2dlbmV0aWNzPC9rZXl3b3JkPjxrZXl3b3JkPlRyYW5zY3Jp

cHRpb24sIEdlbmV0aWM8L2tleXdvcmQ+PGtleXdvcmQ+WGVub3B1czwva2V5d29yZD48L2tleXdv

cmRzPjxkYXRlcz48eWVhcj4xOTkxPC95ZWFyPjxwdWItZGF0ZXM+PGRhdGU+Tm92PC9kYXRlPjwv

cHViLWRhdGVzPjwvZGF0ZXM+PGlzYm4+MDI2MS00MTg5IChQcmludCkmI3hEOzAyNjEtNDE4OSAo

TGlua2luZyk8L2lzYm4+PGFjY2Vzc2lvbi1udW0+MTgzMzE4NTwvYWNjZXNzaW9uLW51bT48dXJs

cz48L3VybHM+PGN1c3RvbTI+UE1DNDUzMDU3PC9jdXN0b20yPjxyZW1vdGUtZGF0YWJhc2UtcHJv

dmlkZXI+TkxNPC9yZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+PGxhbmd1YWdlPmVuZzwvbGFuZ3Vh

Z2U+PC9yZWNvcmQ+PC9DaXRlPjxDaXRlPjxBdXRob3I+SmVmZnJleTwvQXV0aG9yPjxZZWFyPjE5

OTU8L1llYXI+PFJlY051bT40OTM8L1JlY051bT48cmVjb3JkPjxyZWMtbnVtYmVyPjQ5MzwvcmVj

LW51bWJlcj48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIgZGItaWQ9Incyd2Z4YWZlNnZhOXo1

ZWV2Mmw1NWFhOHN4c2E1OTllZXYycyI+NDkzPC9rZXk+PC9mb3JlaWduLWtleXM+PHJlZi10eXBl

IG5hbWU9IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBlPjxjb250cmlidXRvcnM+PGF1dGhv

cnM+PGF1dGhvcj5KZWZmcmV5LCBQLiBELjwvYXV0aG9yPjxhdXRob3I+UnVzc28sIEEuIEEuPC9h

dXRob3I+PGF1dGhvcj5Qb2x5YWssIEsuPC9hdXRob3I+PGF1dGhvcj5HaWJicywgRS48L2F1dGhv

cj48YXV0aG9yPkh1cndpdHosIEouPC9hdXRob3I+PGF1dGhvcj5NYXNzYWd1ZSwgSi48L2F1dGhv

cj48YXV0aG9yPlBhdmxldGljaCwgTi4gUC48L2F1dGhvcj48L2F1dGhvcnM+PC9jb250cmlidXRv

cnM+PGF1dGgtYWRkcmVzcz5DZWxsdWxhciBCaW9jaGVtaXN0cnkgYW5kIEJpb3BoeXNpY3MgUHJv

Z3JhbSwgTWVtb3JpYWwgU2xvYW4tS2V0dGVyaW5nIENhbmNlciBDZW50ZXIsIE5ldyBZb3JrLCBO

ZXcgWW9yayAxMDAyMSwgVVNBLjwvYXV0aC1hZGRyZXNzPjx0aXRsZXM+PHRpdGxlPk1lY2hhbmlz

bSBvZiBDREsgYWN0aXZhdGlvbiByZXZlYWxlZCBieSB0aGUgc3RydWN0dXJlIG9mIGEgY3ljbGlu

QS1DREsyIGNvbXBsZXg8L3RpdGxlPjxzZWNvbmRhcnktdGl0bGU+TmF0dXJlPC9zZWNvbmRhcnkt

dGl0bGU+PGFsdC10aXRsZT5OYXR1cmU8L2FsdC10aXRsZT48L3RpdGxlcz48cGVyaW9kaWNhbD48

ZnVsbC10aXRsZT5OYXR1cmU8L2Z1bGwtdGl0bGU+PGFiYnItMT5OYXR1cmU8L2FiYnItMT48L3Bl

cmlvZGljYWw+PGFsdC1wZXJpb2RpY2FsPjxmdWxsLXRpdGxlPk5hdHVyZTwvZnVsbC10aXRsZT48

YWJici0xPk5hdHVyZTwvYWJici0xPjwvYWx0LXBlcmlvZGljYWw+PHBhZ2VzPjMxMy0yMDwvcGFn

ZXM+PHZvbHVtZT4zNzY8L3ZvbHVtZT48bnVtYmVyPjY1Mzg8L251bWJlcj48ZWRpdGlvbj4xOTk1

LzA3LzI3PC9lZGl0aW9uPjxrZXl3b3Jkcz48a2V5d29yZD5BZGVub3NpbmUgVHJpcGhvc3BoYXRl

L2NoZW1pc3RyeS9tZXRhYm9saXNtPC9rZXl3b3JkPjxrZXl3b3JkPkFsbG9zdGVyaWMgUmVndWxh

dGlvbjwva2V5d29yZD48a2V5d29yZD5BbWlubyBBY2lkIFNlcXVlbmNlPC9rZXl3b3JkPjxrZXl3

b3JkPkJpbmRpbmcgU2l0ZXM8L2tleXdvcmQ+PGtleXdvcmQ+Q0RDMi1DREMyOCBLaW5hc2VzPC9r

ZXl3b3JkPjxrZXl3b3JkPkNvbXB1dGVyIEdyYXBoaWNzPC9rZXl3b3JkPjxrZXl3b3JkPkNyeXN0

YWxsb2dyYXBoeSwgWC1SYXk8L2tleXdvcmQ+PGtleXdvcmQ+Q3ljbGljIEFNUC1EZXBlbmRlbnQg

UHJvdGVpbiBLaW5hc2VzL2NoZW1pc3RyeTwva2V5d29yZD48a2V5d29yZD5DeWNsaW4tRGVwZW5k

ZW50IEtpbmFzZSAyPC9rZXl3b3JkPjxrZXl3b3JkPkN5Y2xpbi1EZXBlbmRlbnQgS2luYXNlcy8g

Y2hlbWlzdHJ5L21ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+Q3ljbGlucy8gY2hlbWlzdHJ5

L21ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+RW56eW1lIEFjdGl2YXRpb248L2tleXdvcmQ+

PGtleXdvcmQ+RXNjaGVyaWNoaWEgY29saTwva2V5d29yZD48a2V5d29yZD5IdW1hbnM8L2tleXdv

cmQ+PGtleXdvcmQ+TW9sZWN1bGFyIFNlcXVlbmNlIERhdGE8L2tleXdvcmQ+PGtleXdvcmQ+UGhv

c3Bob3J5bGF0aW9uPC9rZXl3b3JkPjxrZXl3b3JkPlByb3RlaW4gQmluZGluZzwva2V5d29yZD48

a2V5d29yZD5Qcm90ZWluIENvbmZvcm1hdGlvbjwva2V5d29yZD48a2V5d29yZD5Qcm90ZWluIEZv

bGRpbmc8L2tleXdvcmQ+PGtleXdvcmQ+UHJvdGVpbi1TZXJpbmUtVGhyZW9uaW5lIEtpbmFzZXMv

IGNoZW1pc3RyeS9tZXRhYm9saXNtPC9rZXl3b3JkPjxrZXl3b3JkPlJlY29tYmluYW50IFByb3Rl

aW5zL2NoZW1pc3RyeTwva2V5d29yZD48a2V5d29yZD5UaHJlb25pbmUvY2hlbWlzdHJ5PC9rZXl3

b3JkPjwva2V5d29yZHM+PGRhdGVzPjx5ZWFyPjE5OTU8L3llYXI+PHB1Yi1kYXRlcz48ZGF0ZT5K

dWwgMjc8L2RhdGU+PC9wdWItZGF0ZXM+PC9kYXRlcz48aXNibj4wMDI4LTA4MzYgKFByaW50KSYj

eEQ7MDAyOC0wODM2IChMaW5raW5nKTwvaXNibj48YWNjZXNzaW9uLW51bT43NjMwMzk3PC9hY2Nl

c3Npb24tbnVtPjx1cmxzPjwvdXJscz48ZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+MTAuMTAzOC8z

NzYzMTNhMDwvZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+PHJlbW90ZS1kYXRhYmFzZS1wcm92aWRl

cj5OTE08L3JlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj48bGFuZ3VhZ2U+ZW5nPC9sYW5ndWFnZT48

L3JlY29yZD48L0NpdGU+PENpdGU+PEF1dGhvcj5EaWVobDwvQXV0aG9yPjxZZWFyPjE5OTc8L1ll

YXI+PFJlY051bT40OTI8L1JlY051bT48cmVjb3JkPjxyZWMtbnVtYmVyPjQ5MjwvcmVjLW51bWJl

cj48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIgZGItaWQ9Incyd2Z4YWZlNnZhOXo1ZWV2Mmw1

NWFhOHN4c2E1OTllZXYycyI+NDkyPC9rZXk+PC9mb3JlaWduLWtleXM+PHJlZi10eXBlIG5hbWU9

IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBlPjxjb250cmlidXRvcnM+PGF1dGhvcnM+PGF1

dGhvcj5EaWVobCwgSi4gQS48L2F1dGhvcj48YXV0aG9yPlNoZXJyLCBDLiBKLjwvYXV0aG9yPjwv

YXV0aG9ycz48L2NvbnRyaWJ1dG9ycz48YXV0aC1hZGRyZXNzPkhvd2FyZCBIdWdoZXMgTWVkaWNh

bCBJbnN0aXR1dGUsIERlcGFydG1lbnQgb2YgVHVtb3IgQ2VsbCBCaW9sb2d5LCBTdC4gSnVkZSBD

aGlsZHJlbiZhcG9zO3MgUmVzZWFyY2ggSG9zcGl0YWwsIE1lbXBoaXMsIFRlbm5lc3NlZSAzODEw

NSwgVVNBLjwvYXV0aC1hZGRyZXNzPjx0aXRsZXM+PHRpdGxlPkEgZG9taW5hbnQtbmVnYXRpdmUg

Y3ljbGluIEQxIG11dGFudCBwcmV2ZW50cyBudWNsZWFyIGltcG9ydCBvZiBjeWNsaW4tZGVwZW5k

ZW50IGtpbmFzZSA0IChDREs0KSBhbmQgaXRzIHBob3NwaG9yeWxhdGlvbiBieSBDREstYWN0aXZh

dGluZyBraW5hc2U8L3RpdGxlPjxzZWNvbmRhcnktdGl0bGU+TW9sIENlbGwgQmlvbDwvc2Vjb25k

YXJ5LXRpdGxlPjxhbHQtdGl0bGU+TW9sZWN1bGFyIGFuZCBjZWxsdWxhciBiaW9sb2d5PC9hbHQt

dGl0bGU+PC90aXRsZXM+PHBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+TW9sIENlbGwgQmlvbDwvZnVs

bC10aXRsZT48YWJici0xPk1vbGVjdWxhciBhbmQgY2VsbHVsYXIgYmlvbG9neTwvYWJici0xPjwv

cGVyaW9kaWNhbD48YWx0LXBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+TW9sIENlbGwgQmlvbDwvZnVs

bC10aXRsZT48YWJici0xPk1vbGVjdWxhciBhbmQgY2VsbHVsYXIgYmlvbG9neTwvYWJici0xPjwv

YWx0LXBlcmlvZGljYWw+PHBhZ2VzPjczNjItNzQ8L3BhZ2VzPjx2b2x1bWU+MTc8L3ZvbHVtZT48

bnVtYmVyPjEyPC9udW1iZXI+PGVkaXRpb24+MTk5Ny8xMi8zMTwvZWRpdGlvbj48a2V5d29yZHM+

PGtleXdvcmQ+M1QzIENlbGxzPC9rZXl3b3JkPjxrZXl3b3JkPkFuaW1hbHM8L2tleXdvcmQ+PGtl

eXdvcmQ+QmFzZSBTZXF1ZW5jZTwva2V5d29yZD48a2V5d29yZD5CaW9sb2dpY2FsIFRyYW5zcG9y

dCwgQWN0aXZlL2dlbmV0aWNzPC9rZXl3b3JkPjxrZXl3b3JkPkNlbGwgQ3ljbGUvZ2VuZXRpY3Mv

cGh5c2lvbG9neTwva2V5d29yZD48a2V5d29yZD5DZWxsIE51Y2xldXMvbWV0YWJvbGlzbTwva2V5

d29yZD48a2V5d29yZD5DeWNsaW4gRDEvY2hlbWlzdHJ5LyBnZW5ldGljcy8gbWV0YWJvbGlzbTwv

a2V5d29yZD48a2V5d29yZD5DeWNsaW4tRGVwZW5kZW50IEtpbmFzZSA0PC9rZXl3b3JkPjxrZXl3

b3JkPkN5Y2xpbi1EZXBlbmRlbnQgS2luYXNlcy9jaGVtaXN0cnkvIG1ldGFib2xpc208L2tleXdv

cmQ+PGtleXdvcmQ+Q3l0b3BsYXNtL21ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+RE5BIFBy

aW1lcnMvZ2VuZXRpY3M8L2tleXdvcmQ+PGtleXdvcmQ+TWFjcm9tb2xlY3VsYXIgU3Vic3RhbmNl

czwva2V5d29yZD48a2V5d29yZD5NaWNlPC9rZXl3b3JkPjxrZXl3b3JkPk11dGF0aW9uPC9rZXl3

b3JkPjxrZXl3b3JkPlBob3NwaG9yeWxhdGlvbjwva2V5d29yZD48a2V5d29yZD5Qb2x5bWVyYXNl

IENoYWluIFJlYWN0aW9uPC9rZXl3b3JkPjxrZXl3b3JkPlByb3RlaW4gQ29uZm9ybWF0aW9uPC9r

ZXl3b3JkPjxrZXl3b3JkPlByb3RlaW4tU2VyaW5lLVRocmVvbmluZSBLaW5hc2VzLyBtZXRhYm9s

aXNtPC9rZXl3b3JkPjxrZXl3b3JkPlByb3RvLU9uY29nZW5lIFByb3RlaW5zPC9rZXl3b3JkPjxr

ZXl3b3JkPlRyYW5zZmVjdGlvbjwva2V5d29yZD48L2tleXdvcmRzPjxkYXRlcz48eWVhcj4xOTk3

PC95ZWFyPjxwdWItZGF0ZXM+PGRhdGU+RGVjPC9kYXRlPjwvcHViLWRhdGVzPjwvZGF0ZXM+PGlz

Ym4+MDI3MC03MzA2IChQcmludCkmI3hEOzAyNzAtNzMwNiAoTGlua2luZyk8L2lzYm4+PGFjY2Vz

c2lvbi1udW0+OTM3Mjk2NzwvYWNjZXNzaW9uLW51bT48dXJscz48L3VybHM+PGN1c3RvbTI+UE1D

MjMyNTkyPC9jdXN0b20yPjxyZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+TkxNPC9yZW1vdGUtZGF0

YWJhc2UtcHJvdmlkZXI+PGxhbmd1YWdlPmVuZzwvbGFuZ3VhZ2U+PC9yZWNvcmQ+PC9DaXRlPjwv

RW5kTm90ZT5=

ADDIN EN.CITE.DATA [83-85]. САК состоит из трех субъединиц: CDK7, циклин H и белка Mat1, который активирует комплекс циклин H/CDK7. Связывание с циклином приводит к конформационным изменениям в CDK, которые делают возможным фосфорилирование CDK с помощью CAK ADDIN EN.CITE <EndNote><Cite><Author>Porter</Author><Year>2003</Year><RecNum>471</RecNum><DisplayText>[86]</DisplayText><record><rec-number>471</rec-number><foreign-keys><key app="EN" db-id="w2wfxafe6va9z5eev2l55aa8sxsa599eev2s">471</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Porter, L. A.</author><author>Donoghue, D. J.</author></authors></contributors><auth-address>Department of Chemistry &amp; Biochemistry, University of California, San Diego, La Jolla, CA 92093-0367, USA.</auth-address><titles><title>Cyclin B1 and CDK1: nuclear localization and upstream regulators</title><secondary-title>Prog Cell Cycle Res</secondary-title><alt-title>Progress in cell cycle research</alt-title></titles><periodical><full-title>Prog Cell Cycle Res</full-title><abbr-1>Progress in cell cycle research</abbr-1></periodical><alt-periodical><full-title>Prog Cell Cycle Res</full-title><abbr-1>Progress in cell cycle research</abbr-1></alt-periodical><pages>335-47</pages><volume>5</volume><edition>2003/11/05</edition><keywords><keyword>Active Transport, Cell Nucleus/drug effects/genetics</keyword><keyword>Animals</keyword><keyword>Antineoplastic Agents/pharmacology</keyword><keyword>CDC2 Protein Kinase/drug effects/ genetics/metabolism</keyword><keyword>Cell Cycle/drug effects/ physiology</keyword><keyword>Cell Nucleus/drug effects/ metabolism</keyword><keyword>Cyclin B/drug effects/ genetics/metabolism</keyword><keyword>Cyclin B1</keyword><keyword>Drug Evaluation, Preclinical</keyword><keyword>Humans</keyword><keyword>Phosphorylation/drug effects</keyword></keywords><dates><year>2003</year></dates><isbn>1087-2957 (Print)&#xD;1087-2957 (Linking)</isbn><accession-num>14593728</accession-num><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[86]. Активность CAK-киназы постоянна на протяжении всего клеточного цикла ADDIN EN.CITE <EndNote><Cite><Author>Lolli</Author><Year>2005</Year><RecNum>465</RecNum><DisplayText>[87]</DisplayText><record><rec-number>465</rec-number><foreign-keys><key app="EN" db-id="w2wfxafe6va9z5eev2l55aa8sxsa599eev2s">465</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lolli, G.</author><author>Johnson, L. N.</author></authors></contributors><auth-address>Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford, Oxford, UK. graziano@biop.ox.ac.uk</auth-address><titles><title>CAK-Cyclin-dependent Activating Kinase: a key kinase in cell cycle control and a target for drugs?</title><secondary-title>Cell Cycle</secondary-title><alt-title>Cell cycle (Georgetown, Tex.)</alt-title></titles><periodical><full-title>Cell Cycle</full-title><abbr-1>Cell cycle (Georgetown, Tex.)</abbr-1></periodical><alt-periodical><full-title>Cell Cycle</full-title><abbr-1>Cell cycle (Georgetown, Tex.)</abbr-1></alt-periodical><pages>572-7</pages><volume>4</volume><number>4</number><edition>2005/05/07</edition><keywords><keyword>Animals</keyword><keyword>Antineoplastic Agents/pharmacology</keyword><keyword>Cell Cycle</keyword><keyword>Cyclin-Dependent Kinases/metabolism/ physiology</keyword><keyword>Gene Expression Regulation</keyword><keyword>Humans</keyword><keyword>Models, Biological</keyword><keyword>Models, Molecular</keyword><keyword>Neoplasms/ therapy</keyword><keyword>Receptor Protein-Tyrosine Kinases/ physiology</keyword></keywords><dates><year>2005</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>1551-4005 (Electronic)&#xD;1551-4005 (Linking)</isbn><accession-num>15876871</accession-num><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[87].

lefttopРисунок 1.1. Основные фазо-специфические комплексы циклинов с циклин-зависимыми киназами у позвоночных. Из ADDIN EN.CITE <EndNote><Cite><Author>Coller</Author><Year>2007</Year><RecNum>170</RecNum><DisplayText>[82]</DisplayText><record><rec-number>170</rec-number><foreign-keys><key app="EN" db-id="w2wfxafe6va9z5eev2l55aa8sxsa599eev2s">170</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Coller, H. A.</author></authors></contributors><auth-address>Department of Molecular Biology, Lewis Thomas Laboratory, Room 140, Princeton University, Princeton, New Jersey 08544-1014, USA. hcoller@princeton.edu</auth-address><titles><title>What&apos;s taking so long? S-phase entry from quiescence versus proliferation</title><secondary-title>Nat Rev Mol Cell Biol</secondary-title><alt-title>Nature reviews. Molecular cell biology</alt-title></titles><periodical><full-title>Nat Rev Mol Cell Biol</full-title><abbr-1>Nature reviews. Molecular cell biology</abbr-1></periodical><alt-periodical><full-title>Nat Rev Mol Cell Biol</full-title><abbr-1>Nature reviews. Molecular cell biology</abbr-1></alt-periodical><pages>667-70</pages><volume>8</volume><number>8</number><edition>2007/07/20</edition><keywords><keyword>Animals</keyword><keyword>DNA Replication/ physiology</keyword><keyword>G1 Phase/ physiology</keyword><keyword>Humans</keyword><keyword>S Phase/ physiology</keyword><keyword>Time Factors</keyword></keywords><dates><year>2007</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>1471-0072 (Print)&#xD;1471-0072 (Linking)</isbn><accession-num>17637736</accession-num><urls></urls><electronic-resource-num>10.1038/nrm2223</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[82], с изменениями. См. пояснения в тексте.

На сегодняшний день насчитывается два семейства CKI: INK4 и Cip/Kip. Семейство INK4 включает белки р15, р16, р18 и р19, которые специфически связываются с CDK4/6, препятствуя образованию комплекса с циклином D PEVuZE5vdGU+PENpdGU+PEF1dGhvcj52YW4gZGVuIEhldXZlbDwvQXV0aG9yPjxZZWFyPjIwMDU8

L1llYXI+PFJlY051bT41MDE8L1JlY051bT48RGlzcGxheVRleHQ+Wzg4LCA4OV08L0Rpc3BsYXlU

ZXh0PjxyZWNvcmQ+PHJlYy1udW1iZXI+NTAxPC9yZWMtbnVtYmVyPjxmb3JlaWduLWtleXM+PGtl

eSBhcHA9IkVOIiBkYi1pZD0idzJ3ZnhhZmU2dmE5ejVlZXYybDU1YWE4c3hzYTU5OWVldjJzIj41

MDE8L2tleT48L2ZvcmVpZ24ta2V5cz48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4x

NzwvcmVmLXR5cGU+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPnZhbiBkZW4gSGV1dmVs

LCBTLjwvYXV0aG9yPjwvYXV0aG9ycz48L2NvbnRyaWJ1dG9ycz48YXV0aC1hZGRyZXNzPk1hc3Nh

Y2h1c2V0dHMgR2VuZXJhbCBIb3NwaXRhbCBDYW5jZXIgQ2VudGVyLCBIYXJ2YXJkIE1lZGljYWwg

U2Nob29sLCBDaGFybGVzdG93biwgTUEgMDIxMjksIFVTQS4gaGV1dmVsQGhlbGl4Lm1naC5oYXJ2

YXJkLmVkdTwvYXV0aC1hZGRyZXNzPjx0aXRsZXM+PHRpdGxlPkNlbGwtY3ljbGUgcmVndWxhdGlv

bjwvdGl0bGU+PHNlY29uZGFyeS10aXRsZT5Xb3JtQm9vazwvc2Vjb25kYXJ5LXRpdGxlPjxhbHQt

dGl0bGU+V29ybUJvb2sgOiB0aGUgb25saW5lIHJldmlldyBvZiBDLiBlbGVnYW5zIGJpb2xvZ3k8

L2FsdC10aXRsZT48L3RpdGxlcz48cGVyaW9kaWNhbD48ZnVsbC10aXRsZT5Xb3JtQm9vazwvZnVs

bC10aXRsZT48YWJici0xPldvcm1Cb29rIDogdGhlIG9ubGluZSByZXZpZXcgb2YgQy4gZWxlZ2Fu

cyBiaW9sb2d5PC9hYmJyLTE+PC9wZXJpb2RpY2FsPjxhbHQtcGVyaW9kaWNhbD48ZnVsbC10aXRs

ZT5Xb3JtQm9vazwvZnVsbC10aXRsZT48YWJici0xPldvcm1Cb29rIDogdGhlIG9ubGluZSByZXZp

ZXcgb2YgQy4gZWxlZ2FucyBiaW9sb2d5PC9hYmJyLTE+PC9hbHQtcGVyaW9kaWNhbD48cGFnZXM+

MS0xNjwvcGFnZXM+PGVkaXRpb24+MjAwNy8xMi8wMTwvZWRpdGlvbj48a2V5d29yZHM+PGtleXdv

cmQ+QW5pbWFsczwva2V5d29yZD48a2V5d29yZD5DYWVub3JoYWJkaXRpcyBlbGVnYW5zLyBjeXRv

bG9neS9lbWJyeW9sb2d5L2dlbmV0aWNzPC9rZXl3b3JkPjxrZXl3b3JkPkNlbGwgQ3ljbGUvZ2Vu

ZXRpY3MvIHBoeXNpb2xvZ3k8L2tleXdvcmQ+PC9rZXl3b3Jkcz48ZGF0ZXM+PHllYXI+MjAwNTwv

eWVhcj48L2RhdGVzPjxpc2JuPjE1NTEtODUwNyAoRWxlY3Ryb25pYykmI3hEOzE1NTEtODUwNyAo

TGlua2luZyk8L2lzYm4+PGFjY2Vzc2lvbi1udW0+MTgwNTA0MjI8L2FjY2Vzc2lvbi1udW0+PHVy

bHM+PC91cmxzPjxlbGVjdHJvbmljLXJlc291cmNlLW51bT4xMC4xODk1L3dvcm1ib29rLjEuMjgu

MTwvZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+PHJlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj5OTE08

L3JlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj48bGFuZ3VhZ2U+ZW5nPC9sYW5ndWFnZT48L3JlY29y

ZD48L0NpdGU+PENpdGU+PEF1dGhvcj5Hb2xpYXM8L0F1dGhvcj48WWVhcj4yMDA0PC9ZZWFyPjxS

ZWNOdW0+NTAyPC9SZWNOdW0+PHJlY29yZD48cmVjLW51bWJlcj41MDI8L3JlYy1udW1iZXI+PGZv

cmVpZ24ta2V5cz48a2V5IGFwcD0iRU4iIGRiLWlkPSJ3MndmeGFmZTZ2YTl6NWVldjJsNTVhYThz

eHNhNTk5ZWV2MnMiPjUwMjwva2V5PjwvZm9yZWlnbi1rZXlzPjxyZWYtdHlwZSBuYW1lPSJKb3Vy

bmFsIEFydGljbGUiPjE3PC9yZWYtdHlwZT48Y29udHJpYnV0b3JzPjxhdXRob3JzPjxhdXRob3I+

R29saWFzLCBDLiBILjwvYXV0aG9yPjxhdXRob3I+Q2hhcmFsYWJvcG91bG9zLCBBLjwvYXV0aG9y

PjxhdXRob3I+Q2hhcmFsYWJvcG91bG9zLCBLLjwvYXV0aG9yPjwvYXV0aG9ycz48L2NvbnRyaWJ1

dG9ycz48YXV0aC1hZGRyZXNzPkRlcGFydG1lbnQgb2YgUGh5c2lvbG9neSwgQ2xpbmljYWwgVW5p

dCwgTWVkaWNhbCBGYWN1bHR5LCBVbml2ZXJzaXR5IG9mIElvYW5uaW5hLCBJb2FubmluYSwgR3Jl

ZWNlLjwvYXV0aC1hZGRyZXNzPjx0aXRsZXM+PHRpdGxlPkNlbGwgcHJvbGlmZXJhdGlvbiBhbmQg

Y2VsbCBjeWNsZSBjb250cm9sOiBhIG1pbmkgcmV2aWV3PC90aXRsZT48c2Vjb25kYXJ5LXRpdGxl

PkludCBKIENsaW4gUHJhY3Q8L3NlY29uZGFyeS10aXRsZT48YWx0LXRpdGxlPkludGVybmF0aW9u

YWwgam91cm5hbCBvZiBjbGluaWNhbCBwcmFjdGljZTwvYWx0LXRpdGxlPjwvdGl0bGVzPjxwZXJp

b2RpY2FsPjxmdWxsLXRpdGxlPkludCBKIENsaW4gUHJhY3Q8L2Z1bGwtdGl0bGU+PGFiYnItMT5J

bnRlcm5hdGlvbmFsIGpvdXJuYWwgb2YgY2xpbmljYWwgcHJhY3RpY2U8L2FiYnItMT48L3Blcmlv

ZGljYWw+PGFsdC1wZXJpb2RpY2FsPjxmdWxsLXRpdGxlPkludCBKIENsaW4gUHJhY3Q8L2Z1bGwt

dGl0bGU+PGFiYnItMT5JbnRlcm5hdGlvbmFsIGpvdXJuYWwgb2YgY2xpbmljYWwgcHJhY3RpY2U8

L2FiYnItMT48L2FsdC1wZXJpb2RpY2FsPjxwYWdlcz4xMTM0LTQxPC9wYWdlcz48dm9sdW1lPjU4

PC92b2x1bWU+PG51bWJlcj4xMjwvbnVtYmVyPjxlZGl0aW9uPjIwMDUvMDEvMTQ8L2VkaXRpb24+

PGtleXdvcmRzPjxrZXl3b3JkPkNlbGwgQ3ljbGUvIGdlbmV0aWNzPC9rZXl3b3JkPjxrZXl3b3Jk

PkNlbGwgUHJvbGlmZXJhdGlvbjwva2V5d29yZD48a2V5d29yZD5DZWxsIFRyYW5zZm9ybWF0aW9u

LCBOZW9wbGFzdGljL2dlbmV0aWNzPC9rZXl3b3JkPjxrZXl3b3JkPkN5Y2xpbi1EZXBlbmRlbnQg

S2luYXNlcy9tZXRhYm9saXNtPC9rZXl3b3JkPjxrZXl3b3JkPkN5Y2xpbnMvbWV0YWJvbGlzbTwv

a2V5d29yZD48a2V5d29yZD5GbG93IEN5dG9tZXRyeTwva2V5d29yZD48a2V5d29yZD5JbW11bm9o

aXN0b2NoZW1pc3RyeTwva2V5d29yZD48a2V5d29yZD5NaXRvc2lzL2dlbmV0aWNzPC9rZXl3b3Jk

PjxrZXl3b3JkPk5lb3BsYXNtcy9wYXRob2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+UHlyaW1pZGlu

ZXMvbWV0YWJvbGlzbTwva2V5d29yZD48L2tleXdvcmRzPjxkYXRlcz48eWVhcj4yMDA0PC95ZWFy

PjxwdWItZGF0ZXM+PGRhdGU+RGVjPC9kYXRlPjwvcHViLWRhdGVzPjwvZGF0ZXM+PGlzYm4+MTM2

OC01MDMxIChQcmludCkmI3hEOzEzNjgtNTAzMSAoTGlua2luZyk8L2lzYm4+PGFjY2Vzc2lvbi1u

dW0+MTU2NDY0MTE8L2FjY2Vzc2lvbi1udW0+PHVybHM+PC91cmxzPjxyZW1vdGUtZGF0YWJhc2Ut

cHJvdmlkZXI+TkxNPC9yZW1vdGUtZGF0YWJhc2UtcHJvdmlkZXI+PGxhbmd1YWdlPmVuZzwvbGFu

Z3VhZ2U+PC9yZWNvcmQ+PC9DaXRlPjwvRW5kTm90ZT4A

ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj52YW4gZGVuIEhldXZlbDwvQXV0aG9yPjxZZWFyPjIwMDU8

L1llYXI+PFJlY051bT41MDE8L1JlY051bT48RGlzcGxheVRleHQ+Wzg4LCA4OV08L0Rpc3BsYXlU

ZXh0PjxyZWNvcmQ+PHJlYy1udW1iZXI+NTAxPC9yZWMtbnVtYmVyPjxmb3JlaWduLWtleXM+PGtl

eSBhcHA9IkVOIiBkYi1pZD0idzJ3ZnhhZmU2dmE5ejVlZXYybDU1YWE4c3hzYTU5OWVldjJzIj41

MDE8L2tleT48L2ZvcmVpZ24ta2V5cz48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4x

NzwvcmVmLXR5cGU+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPnZhbiBkZW4gSGV1dmVs

LCBTLjwvYXV0aG9yPjwvYXV0aG9ycz48L2NvbnRyaWJ1dG9ycz48YXV0aC1hZGRyZXNzPk1hc3Nh

Y2h1c2V0dHMgR2VuZXJhbCBIb3NwaXRhbCBDYW5jZXIgQ2VudGVyLCBIYXJ2YXJkIE1lZGljYWwg

U2Nob29sLCBDaGFybGVzdG93biwgTUEgMDIxMjksIFVTQS4gaGV1dmVsQGhlbGl4Lm1naC5oYXJ2

YXJkLmVkdTwvYXV0aC1hZGRyZXNzPjx0aXRsZXM+PHRpdGxlPkNlbGwtY3ljbGUgcmVndWxhdGlv

bjwvdGl0bGU+PHNlY29uZGFyeS10aXRsZT5Xb3JtQm9vazwvc2Vjb25kYXJ5LXRpdGxlPjxhbHQt

dGl0bGU+V29ybUJvb2sgOiB0aGUgb25saW5lIHJldmlldyBvZiBDLiBlbGVnYW5zIGJpb2xvZ3k8

L2FsdC10aXRsZT48L3RpdGxlcz48cGVyaW9kaWNhbD48ZnVsbC10aXRsZT5Xb3JtQm9vazwvZnVs

bC10aXRsZT48YWJici0xPldvcm1Cb29rIDogdGhlIG9ubGluZSByZXZpZXcgb2YgQy4gZWxlZ2Fu

cyBiaW9sb2d5PC9hYmJyLTE+PC9wZXJpb2RpY2FsPjxhbHQtcGVyaW9kaWNhbD48ZnVsbC10aXRs

ZT5Xb3JtQm9vazwvZnVsbC10aXRsZT48YWJici0xPldvcm1Cb29rIDogdGhlIG9ubGluZSByZXZp

ZXcgb2YgQy4gZWxlZ2FucyBiaW9sb2d5PC9hYmJyLTE+PC9hbHQtcGVyaW9kaWNhbD48cGFnZXM+

MS0xNjwvcGFnZXM+PGVkaXRpb24+MjAwNy8xMi8wMTwvZWRpdGlvbj48a2V5d29yZHM+PGtleXdv

cmQ+QW5pbWFsczwva2V5d29yZD48a2V5d29yZD5DYWVub3JoYWJkaXRpcyBlbGVnYW5zLyBjeXRv

bG9neS9lbWJyeW9sb2d5L2dlbmV0aWNzPC9rZXl3b3JkPjxrZXl3b3JkPkNlbGwgQ3ljbGUvZ2Vu

ZXRpY3MvIHBoeXNpb2xvZ3k8L2tleXdvcmQ+PC9rZXl3b3Jkcz48ZGF0ZXM+PHllYXI+MjAwNTwv

eWVhcj48L2RhdGVzPjxpc2JuPjE1NTEtODUwNyAoRWxlY3Ryb25pYykmI3hEOzE1NTEtODUwNyAo

TGlua2luZyk8L2lzYm4+PGFjY2Vzc2lvbi1udW0+MTgwNTA0MjI8L2FjY2Vzc2lvbi1udW0+PHVy

bHM+PC91cmxzPjxlbGVjdHJvbmljLXJlc291cmNlLW51bT4xMC4xODk1L3dvcm1ib29rLjEuMjgu

MTwvZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+PHJlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj5OTE08

L3JlbW90ZS1kYXRhYmFzZS1wcm92aWRlcj48bGFuZ3VhZ2U+ZW5nPC9sYW5ndWFnZT48L3JlY29y



Pages:     | 1 | 2 || 4 | 5 |   ...   | 15 |
Похожие работы:

«МИНОБРНАУКИ РОССИЙСКОЙ ФЕДЕРАЦИИНАЦИОНАЛЬНЫЙ ИССЛЕДОВАТЕЛЬСКИЙ ТОМСКИЙ ГОСУДАРСТВЕННЫЙ УНИВЕРСИТЕТУТВЕРЖДАЮ И. о. декана философского факультета Е. В. Борисов _ сентября 2016 г.ПРОГРАММА ВСТУПИТЕЛЬ...»

«Вопросы к зачету по курсу "Природное наследие" Наследие как феномен. Основные признаки наследия. Основные категории наследия: природное, культурное и природно-культурное, нематериальное культурное наследие. Географичность феномена на...»

«План мероприятий в рамках проведения Года экологии в муниципальных образовательных учреждениях городского округа Самара 2017г. № Наименование мероприятий Сроки проведения Ответственные Информационно-организационные мероприятия...»

«Тема : Что нас окружает. Живая и неживая природа, изделия человека. Цель: сформировать у учащихся понятия о живом и неживом в природе и о рукотворном мире ; формировать умения классифицировать предметы; формироват...»

«"М.Тынышпаев атындаы аза клік жне коммуникациялар академиясы" А Атбе клік жне коммуникациялар колледжі М.Тынышпаев атындаы азККА Атбе колледжіні 2016-2017 оу жылындаы трбие жмысыны есебі Атбе, 2016ж "Баланы дрыс трбиелеу бл бізді артты шаымыз, жаман трбиелеу бл бізді келешек асіретіміз" А...»

«БИОТЕРРОРИЗМ: ФАКТЫ И КОМЕНТАРИИ О.М. Карабан, А.М.Дащук* В.П.Корж Харьковская академия последипломного образования Харьковский государственный медицинский университет * Ключевые слова: биопатогены, искусственное распространение, прогнозирование последствий, противобактериологическая защита...»

«Год экологии 2017: план мероприятий в школе ГБОУ №5 Центрального района Куратор Фомина В.В. учитель географии Цель: формирование активной гражданской позиции в сфере экологии у школьников.  Наименование мероприятия Сроки проведения Ответственн...»

«МИНИСТЕРСТВО ОБРАЗОВАНИЯ И НАУКИ РОССИЙСКОЙ ФЕДЕРАЦИИ ФГБОУ ВО Новосибирский национальный исследовательский государственный университет Факультет естественных наук УТВЕРЖДАЮ 75374540005 2306955106045Декан ФЕН НГУ, профессор _ Резников В.А. "_29_"_августа 2010 г. История России Учебно – методический комплекс каф...»

«МБОУ Малозиновьевская основная общеобразовательная школа Урожайность разных сортов картофеля, выращенных на пришкольном участке Исследовательская работа по биологии Выполнили: ученицы 8 класса Шоронова Анна Кузьмичева Надежда Руководитель: Акишенкова З. М. Д.Ма...»

«Утвержден приказом Федеральной службы по экологическому, технологическому и атомному надзору от 25 ноября 2016 г. № 494АДМИНИСТРАТИВНЫЙ РЕГЛАМЕНТПО ПРЕДОСТАВЛЕНИЮ ФЕДЕРАЛЬНОЙ СЛУЖБОЙ ПО ЭКОЛОГИЧЕСКОМУ, ТЕХНОЛОГИЧЕСКОМУ И АТОМНОМУ НАДЗОР...»

«МБОУ "Краснощёковская СОШ № 1" Алтайского края Исследовательская работа по теме: Правильная осанка – залог здоровья. Выполнила: Измайлова Анастасия, ученица 9 "Б" класса Руководитель: Гревцова Валентина Александровна, учитель химии и биологии 2012 г. Введение Приятно смотреть на стройного, подтянутого человека с правильной осанкой: лёг...»

«Введение в феномен посттравматического роста (ПТР) Все мы знаем высказывание, сделанное Ницше 1888 году: Всё в жизни, что меня не убивает, делает меня сильнее. Это выражение заключает в себе суть феномена посттравматического роста (ПТР), который будет рассмотрен с нейробиологической и клинической точек з...»

«-300165-577215Пилотный проект по экологическим проблемам речных бассейнов Даурии и Амура "Высыхающая Даурия" 00Пилотный проект по экологическим проблемам речных бассейнов Даурии и Амура "Высыхающая Даурия" 558736641186...»

«МОСКОВСКИЙ ИНСТИТУТ ЭЛЕКТРОНИКИ И МАТЕМАТИКИ НИУ ВШЭ Кафедра информационных технологий и автоматизированных системПОЯСНИТЕЛЬНАЯ ЗАПИСКА к дипломному проекту На тему: Оценка эффективности выделенных...»

«Приложение №. к договору № от Место для ввода даты.г. Требования в области охраны труда, промышленной безопасности и экологии Общество с ограниченной ответственностью "СИБУР Тольятти" / Акционерное общество "Тольяттисинтез" (ОГР...»

«Вопросы к экзамену по курсу "Ландшафтоведение" для студентов заочной формы обучения специальности 1-33 01 02 "Геоэкология", 1-31 02 01 "География" 2015/2016 учебный год Объект, предмет, цель, задачи ландшафтоведения Ландшафтная сфера и закономерности ее развития. Научные подходы и методы ландшафтоведен...»

«Челябинская область Муниципальное бюджетное учреждение "Центр методического и хозяйственного обеспечения" от 12.12.2012г. Аналитическая справка по итогам проведения школьного этапа всероссийской олимпиады школьников в 2012-2...»

«МИНИСТЕРСТВО ПРИРОДНЫХ РЕСУРСОВ И ЭКОЛОГИИ РОССИЙСКОЙ ФЕДЕРАЦИИФЕДЕРАЛЬНАЯ СЛУЖБА ПО ГИДРОМЕТЕОРОЛОГИИ И МОНИТОРИНГУ ОКРУЖАЮЩЕЙ СРЕДЫ Федеральное государственное бюджетное учреждение "Всероссийский научно-исследовательский институт гидр...»

«Общие сведения о ГИА 2017 Государственная итоговая аттестация в 9 классе Основной Государственный Экзамен (ОГЭ) в 11 классе Единый Государственный Экзамен (ЕГЭ) для отдельных категорий граждан Государственный Выпускной Экзамен (ГВЭ) 3810400685 Государственная итоговая аттестация (ГИА) – это осн...»

«МИНИСТЕРСТВО ОБРАЗОВАНИЯ И НАУКИ РОССИЙСКОЙ ФЕДЕРАЦИИ ФГАОУ ВО "Новосибирский национальный исследовательский государственный университет" Факультет естественных наукУТВЕРЖДАЮ: 997585113665 1143000124460Декан ФЕН НГУ, профессор _ Резников В.А. "29" августа 2014 г. Осн...»

«Российский химико-технологический университет им Д.И.Менделеева Экологические аспекты производства аммиака Мультимедийный курс для средней школы Состоит из двух частей – Информационный файл (Word 2007) и Презентация (Power Point 2007).Работа выполнена коллективом кафедры про...»

«Республиканское государственное казенное учреждение "Учебно – методический центр экологической безопасности и защиты населения" Методические рекомендации Безопасные весенние каникулы Йошкар-Ола 201...»

«Н.Л. ГАЛЕЕВА, г. Москва, школа No 196 Развивающие и диагностические задания в курсе общей биологии // Биология, ПС, №24, 29-37, 2002 Доступность и наглядность объектов изучения долгое время обеспечивали школьн...»

«Промежуточная аттестация 2 семестр 2016-17 уч.годГруппа Квалификационный экзамен Зачеты Экзамены 1 курс 19.02.10 Т-16,Т-26 Т-36, 316326 1. Иностранный язык – диф. зачет2. История – диф. зачет3. Физическая культура – диф.зачет4. ОБЖ – диф. зач...»

«Киселёва Татьяна Игоревна, учитель биологии первой категории МАОУ "СОШ № 7" г. Сорочинска Предмет: биология Класс: 11 УМК: Сивоглазов В. И. Биология. Общая биология. Базовый уровень: учеб. Для 10-11 кл. общеобра...»

«УДК 33:66 Экономическая эффективность плазмохимического метода переработки промышленных и бытовых отходов В.Ю. Рогов, А.В. Зарецкий, Ж.И. Лобанова, М.А. Макаров Национальный и...»

«Пояснительная записка Рабочая программа по биологии для 5 класса составлена на основе федерального государственного образовательного стандарта, учебного плана, примерной программы основного общего образования по биологии с учетом авторской пр...»

«ТЕСТЫ ПО МЕДИЦИНСКОЙ БИОЛОГИИ К ИТОГОВОМУ МОДУЛНОМУ КОНТРОЛЮ № 1 ДЛЯ СТУДЕНТОВ 1 КУРСА I-V МЕДИЦИНСКИХ ФАКУЛЬТЕТОВ 2014-2015 УЧ.ГОД1. Поддержание жизни на любом уровне связано с явлением репродукции. На каком уровне органи...»

«Методические рекомендациипо проведению государственной итоговой аттестации по образовательным программам основного общего образования по всем учебным предметам в форме государственного выпускного экзамена (письменная форма)Москва, 2017 Оглавлен...»








 
2018 www.el.z-pdf.ru - «Библиотека бесплатных материалов - онлайн документы»

Материалы этого сайта размещены для ознакомления, все права принадлежат их авторам.
Если Вы не согласны с тем, что Ваш материал размещён на этом сайте, пожалуйста, напишите нам, мы в течении 2-3 рабочих дней удалим его.