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Keiji Uchiyama, Mitsuru Tomita, Masashi Yano, Junji Chida, Hideyuki Hara, Nandita Rani Das, Anders Nykjaer, Suehiro Sakaguchi
Prions amplify through degradation of the VPS10P sorting receptor sortilin
www.plospathogens.org
www.plospathogens.org
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1 j
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1 TL
-0.004 Tc
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7.4999 0 0 6.6659 214.8661 412.4409 cm
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1 TL
-0.0053 Tc
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(Sc)Tj
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1 j
1 J
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1 TL
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7.4999 0 0 6.6659 429.2787 412.4409 cm
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1 TL
-0.0053 Tc
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(C)Tj
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q
1 j
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7.4999 0 0 6.6659 267.874 399.4582 cm
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1 TL
-0.0053 Tc
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(Sc)Tj
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q
1 j
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1 j
1 J
0 w
7.4999 0 0 6.6659 321.8456 386.4188 cm
BT
/F5 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(C)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 328.9889 381.9968 cm
BT
/F5 1 Tf
1 TL
-0.004 Tc
0 0 Td
(into)Tj
1.8425 0 Td
(PrP)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 362.3244 386.4188 cm
BT
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1 TL
-0.0053 Tc
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(Sc)Tj
ET
Q
q
1 j
1 J
0 w
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1 TL
-0.004 Tc
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1 J
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7.4999 0 0 6.6659 320.7685 373.4362 cm
BT
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1 TL
-0.0053 Tc
0 0 Td
(C)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 327.9685 369.0141 cm
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1 TL
-0.004 Tc
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(could)Tj
2.4491 0 Td
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1.1508 0 Td
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1 j
1 J
0 w
7.4999 0 0 6.6659 555.4204 373.4362 cm
BT
/F5 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(Sc)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 562.1102 369.0141 cm
BT
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1 TL
-0.004 Tc
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(.)Tj
-35.0133 -1.3039 Td
(PrP)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 226.885 360.4535 cm
BT
/F5 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(C)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 234.085 355.9748 cm
BT
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1 TL
-0.004 Tc
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0.8447 0 Td
(normally)Tj
3.8494 0 Td
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5.2214 0 Td
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1 j
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7.4999 0 0 6.6659 399.9118 347.4708 cm
BT
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1 TL
-0.0053 Tc
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(C)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 407.0551 342.9921 cm
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1 TL
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4.2009 0 Td
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6.0435 0 Td
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0.83 0.64 0.02 0 k
(7)Tj
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(].)Tj
1.5987 0 Td
(PrP)Tj
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Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 291.3448 321.4488 cm
BT
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1 TL
-0.0053 Tc
0 0 Td
(Sc)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 300.2456 317.0267 cm
BT
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1 TL
-0.004 Tc
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(is)Tj
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1.389 0 Td
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1.0148 0 Td
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1 j
1 J
0 w
7.4999 0 0 6.6659 333.2409 308.4661 cm
BT
/F5 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(C)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 340.3842 303.9874 cm
BT
/F5 1 Tf
1 TL
-0.004 Tc
0 0 Td
(and)Tj
1.7291 0 Td
(PrP)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 372.5858 308.4661 cm
BT
/F5 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(Sc)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 381.4866 303.9874 cm
BT
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1 TL
-0.004 Tc
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(to)Tj
1.0261 0 Td
(lysosomes)Tj
4.2633 0 Td
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3.4412 0 Td
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3.7927 0 Td
(or)Tj
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1 j
1 J
0 w
7.4999 0 0 6.6659 263.7921 295.4267 cm
BT
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1 TL
-0.0053 Tc
0 0 Td
(Sc)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 272.6929 291.0047 cm
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1 TL
-0.004 Tc
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(impairs)Tj
3.2598 0 Td
(the)Tj
1.4683 0 Td
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4.1556 0 Td
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4.371 0 Td
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ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 430.2425 295.4267 cm
BT
/F5 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(C)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 437.4425 291.0047 cm
BT
/F5 1 Tf
1 TL
-0.004 Tc
0 0 Td
(and)Tj
1.7291 0 Td
(PrP)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 469.644 295.4267 cm
BT
/F5 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(Sc)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 478.5448 291.0047 cm
BT
/F5 1 Tf
1 TL
-0.004 Tc
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1.3889 0 Td
(its)Tj
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3.617 0 Td
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3.4129 0 Td
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5.2214 0 Td
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1.9105 0 Td
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(8)Tj
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(9)Tj
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(deliver)Tj
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(a)Tj
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3.4583 0 Td
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1.0374 0 Td
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(extracellular)Tj
5.1307 0 Td
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3.3108 0 Td
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5.1477 0 Td
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3.203 0 Td
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1.474 0 Td
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-35.4157 -1.2983 Td
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(precursor)Tj
4.0932 0 Td
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3.1521 0 Td
(\(APP\)-cleaving)Tj
6.3156 0 Td
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3.3051 0 Td
(BACE1)Tj
3.1918 0 Td
([)Tj
0.83 0.64 0.02 0 k
(10)Tj
0 g
(])Tj
1.8482 0 Td
(and)Tj
1.7291 0 Td
(the)Tj
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5.5105 0 Td
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2.0579 0 Td
([)Tj
0.83 0.64 0.02 0 k
(11)Tj
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(].)Tj
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2.8006 0 Td
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2.8913 0 Td
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4.3653 0 Td
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(APP)Tj
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1.8425 0 Td
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(12)Tj
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(13)Tj
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2.9594 0 Td
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1.4682 0 Td
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4.9719 0 Td
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(\(AD\))Tj
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(12)Tj
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(15)Tj
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6.3609 0 Td
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1 J
0 w
7.4999 0 0 6.6659 470.7779 139.4645 cm
BT
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1 TL
-0.0053 Tc
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(C)Tj
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1 TL
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7.4999 0 0 6.6659 493.2283 113.4425 cm
BT
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1 TL
-0.0053 Tc
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(Sc)Tj
ET
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7.4999 0 0 6.6659 430.2992 581.4425 cm
BT
/F5 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(C)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 435.2881 577.0204 cm
BT
/F5 1 Tf
1 TL
-0.004 Tc
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(.)Tj
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(Co-immunoprecipitation)Tj
10.369 0 Td
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(antibody)Tj
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(\(Ab\))Tj
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1 j
1 J
0 w
7.4999 0 0 6.6659 554.3433 568.4598 cm
BT
/F5 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(C)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 550.9984 cm
BT
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1 TL
-0.004 Tc
0 0 Td
(with)Tj
1.9955 0 Td
(sortilin,)Tj
3.3109 0 Td
(but)Tj
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(Fig)Tj
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1.6044 0 Td
(S1)Tj
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1 J
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7.4999 0 0 6.6659 485.6881 555.4204 cm
BT
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1 TL
-0.0053 Tc
0 0 Td
(C)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 492.8881 550.9984 cm
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1 TL
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(also)Tj
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(1B)Tj
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1.8198 0 Td
(1C)Tj
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4.405 0 Td
(that)Tj
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1 j
1 J
0 w
7.4999 0 0 6.6659 532.6299 503.433 cm
BT
/F5 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(C)Tj
ET
Q
q
1 j
1 J
0 w
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1 TL
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1.0261 0 Td
(inter-)Tj
-35.0019 -1.3039 Td
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1.372 0 Td
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(cells,)Tj
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(N2a)Tj
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( )Tj
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4.8982 0 Td
(cells)Tj
1.9219 0 Td
(\()Tj
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(S2A)Tj
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(and)Tj
1.7291 0 Td
(S2B)Tj
1.7518 0 Td
(Fig)Tj
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(\).)Tj
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3.1634 0 Td
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1.9842 0 Td
(clearly)Tj
2.8233 0 Td
(indicates)Tj
3.7701 0 Td
(that)Tj
1.7745 0 Td
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q
1 j
1 J
0 w
7.4999 0 0 6.6659 467.433 451.4456 cm
BT
/F5 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(C)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 474.5763 447.0236 cm
BT
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1 TL
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(expression)Tj
4.4673 0 Td
(is)Tj
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6.2646 0 Td
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(anti-PrP)Tj
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(and)Tj
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(PrP)Tj
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Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 245.0267 425.4236 cm
BT
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1 TL
-0.0053 Tc
0 0 Td
(C)Tj
ET
Q
q
1 j
1 J
0 w
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1 TL
-0.004 Tc
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(.)Tj
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4.0762 0 Td
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7.4999 0 0 6.6659 468.737 399.4582 cm
BT
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1 TL
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(C)Tj
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Q
q
1 j
1 J
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1 TL
-0.004 Tc
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(.)Tj
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(Furthermore,)Tj
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7.4999 0 0 6.6659 214.8661 373.4362 cm
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1 TL
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(C)Tj
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7.4999 0 0 6.6659 315.1559 321.4488 cm
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1 TL
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7.4999 0 0 6.6659 334.0913 269.4614 cm
BT
/F5 1 Tf
1 TL
-0.0053 Tc
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(C)Tj
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Q
q
1 j
1 J
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