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Peter C. van den Akker, Anna M. G. Pasmooij, Hans Joenje, Robert M. W. Hofstra, Gerard J. te Meerman, Marcel F. Jonkman
A "late-but-fitter revertant cell" explains the high frequency of revertant mosaicism in epidermolysis bullosa
www.plosone.org
www.plosone.org
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q
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1 J
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BT
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1 TL
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[()]TJ
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Q
q
1 j
1 J
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BT
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[()]TJ
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Q
q
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BT
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1 TL
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(9)Tj
ET
Q
q
1 j
1 J
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BT
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ET
Q
q
1 j
1 J
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7.4999 0 0 6.6659 362.0976 288.2834 cm
BT
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q
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1 J
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[()]TJ
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Q
q
1 j
1 J
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BT
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Q
q
1 j
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(10)Tj
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Q
q
1 j
1 J
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BT
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[()]TJ
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(9)Tj
ET
Q
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(i.e.)Tj
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0.9468 0 Td
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1 J
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7.4999 0 0 6.6659 263.7354 503.8299 cm
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/F6 1 Tf
1 TL
-0.0053 Tc
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q
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/F6 1 Tf
1 TL
-0.004 Tc
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(\(corresponding)Tj
6.4005 0 Td
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1.0205 0 Td
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[()]TJ
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(10)Tj
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Q
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1 J
0 w
7.4999 0 0 6.6659 363.7417 503.8299 cm
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1 TL
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Q
q
1 j
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(BKs\))Tj
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1.0318 0 Td
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1.474 0 Td
(14)Tj
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Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 311.9244 490.8472 cm
BT
/F6 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(th)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 320.3149 486.4251 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
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(cell)Tj
1.559 0 Td
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4.5071 0 Td
(the)Tj
1.4683 0 Td
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q
1 j
1 J
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7.4999 0 0 6.6659 426.6708 490.8472 cm
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/F6 1 Tf
1 TL
-0.0053 Tc
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(14)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 435.9685 486.4251 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
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(=)Tj
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(16,384)Tj
2.8233 0 Td
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3.9628 0 Td
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1.0205 0 Td
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1.1508 0 Td
(reached)Tj
3.3506 0 Td
(before)Tj
2.7438 0 Td
(the)Tj
1.4683 0 Td
(4)Tj
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Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 470.6645 477.8645 cm
BT
/F6 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(th)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 479.0551 473.3858 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
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(week)Tj
2.245 0 Td
(of)Tj
1.0148 0 Td
(embryogenesis)Tj
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([)Tj
0.83 0.64 0.02 0 k
(37)Tj
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1.7802 0 Td
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4.5977 0 Td
[()]TJ
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(that)Tj
1.7801 0 Td
(at)Tj
0.9524 0 Td
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1.6668 0 Td
(have)Tj
2.0579 0 Td
(occurred)Tj
3.7983 0 Td
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1.8028 0 Td
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(~10,000)Tj
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(this)Tj
1.6724 0 Td
(conclusion)Tj
4.5808 0 Td
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3.4696 0 Td
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4.6828 0 Td
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1.627 0 Td
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1.9955 0 Td
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4.7622 0 Td
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5.3233 0 Td
(junctional)Tj
4.2803 0 Td
(EB)Tj
1.3663 0 Td
([)Tj
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(11)Tj
0 g
(].)Tj
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1.9842 0 Td
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5.9471 0 Td
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1.1792 0 Td
(the)Tj
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(developmental)Tj
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(model)Tj
2.7439 0 Td
(itself.)Tj
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2.2677 0 Td
(the)Tj
-35.3817 -1.2983 Td
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2.7439 0 Td
(ignores)Tj
3.1634 0 Td
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(loss)Tj
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(due)Tj
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(normal)Tj
3.1465 0 Td
(biologic)Tj
3.4129 0 Td
(processes,)Tj
4.1952 0 Td
(like)Tj
1.6498 0 Td
(apoptosis)Tj
3.991 0 Td
(and)Tj
1.7291 0 Td
(differentiation.)Tj
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-36.2151 -1.2983 Td
(the)Tj
1.4683 0 Td
(probability)Tj
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(that)Tj
1.7801 0 Td
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(mutations)Tj
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(the)Tj
1.4683 0 Td
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3.4186 0 Td
(of)Tj
1.0147 0 Td
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-35.7502 -1.2982 Td
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1.6668 0 Td
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(an)Tj
1.2019 0 Td
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1.3266 0 Td
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1.9559 0 Td
(used)Tj
2.058 0 Td
(a)Tj
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(con-)Tj
-35.342 -1.2982 Td
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(model)Tj
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1.0375 0 Td
(which)Tj
2.6475 0 Td
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1.3266 0 Td
(assumed)Tj
3.6737 0 Td
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1.7801 0 Td
(90%)Tj
1.9276 0 Td
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1.9219 0 Td
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-35.0926 -1.2983 Td
[()]TJ
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 205.285 315.7228 cm
BT
/F11 1 Tf
1 TL
-0.0053 Tc
0 0 Td
[()]TJ
ET
Q
q
1 j
1 J
0 w
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BT
/F6 1 Tf
1 TL
-0.004 Tc
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(=)Tj
0.7993 0 Td
(1.1)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 230.5133 321.8456 cm
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/F11 1 Tf
1 TL
-0.0053 Tc
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[()]TJ
ET
Q
q
1 j
1 J
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-0.004 Tc
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(,)Tj
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1.0147 0 Td
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[()]TJ
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(10)Tj
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Q
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1 j
1 J
0 w
7.4999 0 0 6.6659 471.9685 321.8456 cm
BT
/F6 1 Tf
1 TL
-0.0053 Tc
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(9)Tj
ET
Q
q
1 j
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BT
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-0.004 Tc
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(\(255)Tj
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1.4683 0 Td
(36)Tj
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[()]TJ
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(10)Tj
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Q
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1 j
1 J
0 w
7.4999 0 0 6.6659 353.7637 308.8629 cm
BT
/F6 1 Tf
1 TL
-0.0053 Tc
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(9)Tj
ET
Q
q
1 j
1 J
0 w
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BT
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1.8368 0 Td
(of)Tj
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(19.6)Tj
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[()]TJ
/F6 1 Tf
(10)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 526.8472 308.8629 cm
BT
/F6 1 Tf
1 TL
-0.0053 Tc
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(6)Tj
ET
Q
q
1 j
1 J
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BT
/F6 1 Tf
1 TL
-0.004 Tc
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(mitoses)Tj
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(\(152)Tj
1.9842 0 Td
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(2)Tj
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[()]TJ
/F6 1 Tf
(10)Tj
ET
Q
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1 j
1 J
0 w
7.4999 0 0 6.6659 371.3385 295.8236 cm
BT
/F6 1 Tf
1 TL
-0.0053 Tc
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(6)Tj
ET
Q
q
1 j
1 J
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BT
/F6 1 Tf
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-0.004 Tc
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(cells)Tj
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(of)Tj
1.0148 0 Td
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(1)Tj
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7.4999 0 0 6.6659 432.3968 295.8236 cm
BT
/F6 1 Tf
1 TL
-0.0053 Tc
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(2)Tj
ET
Q
q
1 j
1 J
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BT
/F6 1 Tf
1 TL
-0.004 Tc
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(recognizable)Tj
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(revertant)Tj
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2.914 0 Td
(then)Tj
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(no)Tj
1.2756 0 Td
(later)Tj
1.9899 0 Td
(than)Tj
2.0296 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4683 0 Td
(103)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 366.4062 269.8582 cm
BT
/F6 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(rd)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 375.307 265.3795 cm
BT
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261.7002 499.8898 l
f*
507.882 521.3897 m
507.882 499.3897 l
507.382 499.3897 l
507.382 521.3897 l
f*
507.382 499.3897 m
262.2002 499.3897 l
262.2002 499.8898 l
507.382 499.8898 l
f*
576 499.3897 m
507.882 499.3897 l
507.882 499.8898 l
576 499.8898 l
f*
262.2002 499.3897 m
262.2002 486.8898 l
261.7002 486.8898 l
261.7002 499.3897 l
f*
261.7002 486.8898 m
200.0001 486.8898 l
200.0001 487.3898 l
261.7002 487.3898 l
f*
507.882 499.3897 m
507.882 486.8898 l
507.382 486.8898 l
507.382 499.3897 l
f*
507.382 486.8898 m
262.2002 486.8898 l
262.2002 487.3898 l
507.382 487.3898 l
f*
576 486.8898 m
507.882 486.8898 l
507.882 487.3898 l
576 487.3898 l
f*
262.2002 486.8898 m
262.2002 464.8898 l
261.7002 464.8898 l
261.7002 486.8898 l
f*
261.7002 464.8898 m
200.0001 464.8898 l
200.0001 465.3899 l
261.7002 465.3899 l
f*
507.882 486.8898 m
507.882 464.8898 l
507.382 464.8898 l
507.382 486.8898 l
f*
507.382 464.8898 m
262.2002 464.8898 l
262.2002 465.3899 l
507.382 465.3899 l
f*
576 464.8898 m
507.882 464.8898 l
507.882 465.3899 l
576 465.3899 l
f*
262.2002 464.8898 m
262.2002 442.8899 l
261.7002 442.8899 l
261.7002 464.8898 l
f*
261.7002 442.8899 m
200.0001 442.8899 l
200.0001 443.3899 l
261.7002 443.3899 l
f*
507.882 464.8898 m
507.882 442.8899 l
507.382 442.8899 l
507.382 464.8898 l
f*
507.382 442.8899 m
262.2002 442.8899 l
262.2002 443.3899 l
507.382 443.3899 l
f*
576 442.8899 m
507.882 442.8899 l
507.882 443.3899 l
576 443.3899 l
f*
262.2002 442.8899 m
262.2002 420.8899 l
261.7002 420.8899 l
261.7002 442.8899 l
f*
261.7002 420.8899 m
200.0001 420.8899 l
200.0001 421.3899 l
261.7002 421.3899 l
f*
507.882 442.8899 m
507.882 420.8899 l
507.382 420.8899 l
507.382 442.8899 l
f*
507.382 420.8899 m
262.2002 420.8899 l
262.2002 421.3899 l
507.382 421.3899 l
f*
576 420.8899 m
507.882 420.8899 l
507.882 421.3899 l
576 421.3899 l
f*
262.2002 420.8899 m
262.2002 398.8899 l
261.7002 398.8899 l
261.7002 420.8899 l
f*
261.7002 398.8899 m
200.0001 398.8899 l
200.0001 399.39 l
261.7002 399.39 l
f*
507.882 420.8899 m
507.882 398.8899 l
507.382 398.8899 l
507.382 420.8899 l
f*
507.382 398.8899 m
262.2002 398.8899 l
262.2002 399.39 l
507.382 399.39 l
f*
576 398.8899 m
507.882 398.8899 l
507.882 399.39 l
576 399.39 l
f*
262.2002 398.8899 m
262.2002 386.39 l
261.7002 386.39 l
261.7002 398.8899 l
f*
261.7002 386.39 m
200.0001 386.39 l
200.0001 386.89 l
261.7002 386.89 l
f*
507.882 398.8899 m
507.882 386.39 l
507.382 386.39 l
507.382 398.8899 l
f*
507.382 386.39 m
262.2002 386.39 l
262.2002 386.89 l
507.382 386.89 l
f*
576 386.39 m
507.882 386.39 l
507.882 386.89 l
576 386.89 l
f*
262.2002 386.39 m
262.2002 373.89 l
261.7002 373.89 l
261.7002 386.39 l
f*
261.7002 373.89 m
200.0001 373.89 l
200.0001 374.3901 l
261.7002 374.3901 l
f*
507.882 386.39 m
507.882 373.89 l
507.382 373.89 l
507.382 386.39 l
f*
507.382 373.89 m
262.2002 373.89 l
262.2002 374.3901 l
507.382 374.3901 l
f*
576 373.89 m
507.882 373.89 l
507.882 374.3901 l
576 374.3901 l
f*
262.2002 373.89 m
262.2002 351.8901 l
261.7002 351.8901 l
261.7002 373.89 l
f*
261.7002 351.8901 m
200.0001 351.8901 l
200.0001 352.3901 l
261.7002 352.3901 l
f*
507.882 373.89 m
507.882 351.8901 l
507.382 351.8901 l
507.382 373.89 l
f*
507.382 351.8901 m
262.2002 351.8901 l
262.2002 352.3901 l
507.382 352.3901 l
f*
576 351.8901 m
507.882 351.8901 l
507.882 352.3901 l
576 352.3901 l
f*
262.2002 351.8901 m
262.2002 329.3722 l
261.7002 329.3722 l
261.7002 351.8901 l
f*
261.7002 329.3722 m
200.0001 329.3722 l
200.0001 329.8723 l
261.7002 329.8723 l
f*
507.882 351.8901 m
507.882 329.3722 l
507.382 329.3722 l
507.382 351.8901 l
f*
507.382 329.3722 m
262.2002 329.3722 l
262.2002 329.8723 l
507.382 329.8723 l
f*
576 329.3722 m
507.882 329.3722 l
507.882 329.8723 l
576 329.8723 l
f*
262.2002 329.3722 m
262.2002 306.8544 l
261.7002 306.8544 l
261.7002 329.3722 l
f*
261.7002 306.8544 m
200.0001 306.8544 l
200.0001 307.3544 l
261.7002 307.3544 l
f*
507.882 329.3722 m
507.882 306.8544 l
507.382 306.8544 l
507.382 329.3722 l
f*
507.382 306.8544 m
262.2002 306.8544 l
262.2002 307.3544 l
507.382 307.3544 l
f*
576 306.8544 m
507.882 306.8544 l
507.882 307.3544 l
576 307.3544 l
f*
262.2002 306.8544 m
262.2002 284.8544 l
261.7002 284.8544 l
261.7002 306.8544 l
f*
261.7002 284.8544 m
200.0001 284.8544 l
200.0001 285.3544 l
261.7002 285.3544 l
f*
507.882 306.8544 m
507.882 284.8544 l
507.382 284.8544 l
507.382 306.8544 l
f*
507.382 284.8544 m
262.2002 284.8544 l
262.2002 285.3544 l
507.382 285.3544 l
f*
576 284.8544 m
507.882 284.8544 l
507.882 285.3544 l
576 285.3544 l
f*
262.2002 284.8544 m
262.2002 262.8544 l
261.7002 262.8544 l
261.7002 284.8544 l
f*
261.7002 262.8544 m
200.0001 262.8544 l
200.0001 263.3545 l
261.7002 263.3545 l
f*
507.882 284.8544 m
507.882 262.8544 l
507.382 262.8544 l
507.382 284.8544 l
f*
507.382 262.8544 m
262.2002 262.8544 l
262.2002 263.3545 l
507.382 263.3545 l
f*
576 262.8544 m
507.882 262.8544 l
507.882 263.3545 l
576 263.3545 l
f*
262.2002 262.8544 m
262.2002 240.8545 l
261.7002 240.8545 l
261.7002 262.8544 l
f*
261.7002 240.8545 m
200.0001 240.8545 l
200.0001 241.3545 l
261.7002 241.3545 l
f*
507.882 262.8544 m
507.882 240.8545 l
507.382 240.8545 l
507.382 262.8544 l
f*
507.382 240.8545 m
262.2002 240.8545 l
262.2002 241.3545 l
507.382 241.3545 l
f*
576 240.8545 m
507.882 240.8545 l
507.882 241.3545 l
576 241.3545 l
f*
262.2002 240.8545 m
262.2002 218.8545 l
261.7002 218.8545 l
261.7002 240.8545 l
f*
261.7002 218.8545 m
200.0001 218.8545 l
200.0001 219.3545 l
261.7002 219.3545 l
f*
507.882 240.8545 m
507.882 218.8545 l
507.382 218.8545 l
507.382 240.8545 l
f*
507.382 218.8545 m
262.2002 218.8545 l
262.2002 219.3545 l
507.382 219.3545 l
f*
576 218.8545 m
507.882 218.8545 l
507.882 219.3545 l
576 219.3545 l
f*
262.2002 218.8545 m
262.2002 196.8545 l
261.7002 196.8545 l
261.7002 218.8545 l
f*
261.7002 196.8545 m
200.0001 196.8545 l
200.0001 197.3546 l
261.7002 197.3546 l
f*
507.882 218.8545 m
507.882 196.8545 l
507.382 196.8545 l
507.382 218.8545 l
f*
507.382 196.8545 m
262.2002 196.8545 l
262.2002 197.3546 l
507.382 197.3546 l
f*
576 196.8545 m
507.882 196.8545 l
507.882 197.3546 l
576 197.3546 l
f*
262.2002 196.8545 m
262.2002 174.8546 l
261.7002 174.8546 l
261.7002 196.8545 l
f*
261.7002 174.8546 m
200.0001 174.8546 l
200.0001 175.3546 l
261.7002 175.3546 l
f*
507.882 196.8545 m
507.882 174.8546 l
507.382 174.8546 l
507.382 196.8545 l
f*
507.382 174.8546 m
262.2002 174.8546 l
262.2002 175.3546 l
507.382 175.3546 l
f*
576 174.8546 m
507.882 174.8546 l
507.882 175.3546 l
576 175.3546 l
f*
262.2002 174.8546 m
262.2002 162.3546 l
261.7002 162.3546 l
261.7002 174.8546 l
f*
261.7002 162.3546 m
200.0001 162.3546 l
200.0001 162.8546 l
261.7002 162.8546 l
f*
507.882 174.8546 m
507.882 162.3546 l
507.382 162.3546 l
507.382 174.8546 l
f*
507.382 162.3546 m
262.2002 162.3546 l
262.2002 162.8546 l
507.382 162.8546 l
f*
576 162.3546 m
507.882 162.3546 l
507.882 162.8546 l
576 162.8546 l
f*
262.2002 162.3546 m
262.2002 140.3546 l
261.7002 140.3546 l
261.7002 162.3546 l
f*
261.7002 140.3546 m
200.0001 140.3546 l
200.0001 140.8547 l
261.7002 140.8547 l
f*
507.882 162.3546 m
507.882 140.3546 l
507.382 140.3546 l
507.382 162.3546 l
f*
507.382 140.3546 m
262.2002 140.3546 l
262.2002 140.8547 l
507.382 140.8547 l
f*
576 140.3546 m
507.882 140.3546 l
507.882 140.8547 l
576 140.8547 l
f*
262.2002 140.3546 m
262.2002 118.3547 l
261.7002 118.3547 l
261.7002 140.3546 l
f*
261.7002 118.3547 m
200.0001 118.3547 l
200.0001 118.8547 l
261.7002 118.8547 l
f*
507.882 140.3546 m
507.882 118.3547 l
507.382 118.3547 l
507.382 140.3546 l
f*
507.382 118.3547 m
262.2002 118.3547 l
262.2002 118.8547 l
507.382 118.8547 l
f*
576 118.3547 m
507.882 118.3547 l
507.882 118.8547 l
576 118.8547 l
f*
262.2002 118.3547 m
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261.7002 96.3547 l
261.7002 118.3547 l
f*
261.7002 96.3547 m
200.0001 96.3547 l
200.0001 96.8547 l
261.7002 96.8547 l
f*
507.882 118.3547 m
507.882 96.3547 l
507.382 96.3547 l
507.382 118.3547 l
f*
507.382 96.3547 m
262.2002 96.3547 l
262.2002 96.8547 l
507.382 96.8547 l
f*
576 96.3547 m
507.882 96.3547 l
507.882 96.8547 l
576 96.8547 l
f*
200.0001 96.3547 m
576 96.3547 l
576 95.8547 l
200.0001 95.8547 l
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513.6378 670.7906 m
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f*
513.6378 648.7937 m
521.2913 648.7937 l
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f*
513.6378 570.3307 m
521.2913 570.3307 l
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f*
513.6378 545.3291 m
521.2913 545.3291 l
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f*
513.6378 532.8 m
521.2913 532.8 l
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f*
513.6378 388.2898 m
521.2913 388.2898 l
h
f*
525.4299 388.2898 m
533.0835 388.2898 l
h
f*
513.6378 375.8173 m
521.2913 375.8173 l
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f*
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283.0677 330.8598 m
323.7732 330.8598 l
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283.0677 330.3496 l
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360.6236 307.8425 l
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f*
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7.9999 0 0 7.9999 265.2094 615.4015 cm
BT
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(2)Tj
ET
Q
q
1 j
1 J
0 w
7.9999 0 0 7.9999 394.9795 533.8771 cm
BT
/F6 1 Tf
1 TL
0 0 Td
(skin)Tj
14.4851 0 Td
([)Tj
0.83 0.64 0.02 0 k
(33)Tj
0 g
(])Tj
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(23,146)Tj
2.8488 0 Td
(cells)Tj
4.1387 0 Td
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(keratin)Tj
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(ocytes)Tj
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(mm)Tj
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Q
q
1 j
1 J
0 w
5.9998 0 0 5.3325 390.274 515.4519 cm
BT
/F6 1 Tf
1 TL
0 0 Td
(2)Tj
ET
Q
q
1 j
1 J
0 w
7.9999 0 0 7.9999 394.9795 511.8803 cm
BT
/F6 1 Tf
1 TL
0 0 Td
(skin)Tj
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(in)Tj
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(this)Tj
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(study)Tj
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(1.8)Tj
1.4102 0 Td
(m)Tj
ET
Q
q
1 j
1 J
0 w
5.9998 0 0 5.3325 217.8708 493.4551 cm
BT
/F6 1 Tf
1 TL
0 0 Td
(2)Tj
ET
Q
q
1 j
1 J
0 w
7.9999 0 0 7.9999 265.2094 489.8834 cm
BT
/F6 1 Tf
1 TL
0 0 Td
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3.5008 0 Td
(skin)Tj
1.9134 0 Td
(surface)Tj
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(in)Tj
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(adult)Tj
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(human)Tj
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(body)Tj
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(in)Tj
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(this)Tj
1.6937 0 Td
(study)Tj
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(3.3x10)Tj
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Q
q
1 j
1 J
0 w
5.9998 0 0 5.3325 220.8755 480.9259 cm
BT
/F6 1 Tf
1 TL
0 0 Td
(6)Tj
ET
Q
q
1 j
1 J
0 w
7.9999 0 0 7.9999 225.5811 477.411 cm
BT
/F6 1 Tf
1 TL
0 0 Td
(mm)Tj
ET
Q
q
1 j
1 J
0 w
5.9998 0 0 5.3325 238.6771 480.9259 cm
BT
/F6 1 Tf
1 TL
0 0 Td
(2)Tj
ET
Q
q
1 j
1 J
0 w
7.9999 0 0 7.9999 265.2094 477.411 cm
BT
/F6 1 Tf
1 TL
0 0 Td
(Average)Tj
3.5008 0 Td
(total)Tj
2.0268 0 Td
(DEJ)Tj
1.8708 0 Td
(surface)Tj
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(in)Tj
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(adult)Tj
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(human)Tj
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(body)Tj
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(in)Tj
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(this)Tj
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(study)Tj
-38.8561 -1.5591 Td
(36x10)Tj
ET
Q
q
1 j
1 J
0 w
5.9998 0 0 5.3325 219.0047 458.9291 cm
BT
/F6 1 Tf
1 TL
0 0 Td
(9)Tj
ET
Q
q
1 j
1 J
0 w
7.9999 0 0 7.9999 223.7102 455.4141 cm
BT
/F6 1 Tf
1 TL
0 0 Td
(cells)Tj
5.1874 0 Td
(Average)Tj
3.5008 0 Td
(total)Tj
2.0268 0 Td
(number)Tj
3.437 0 Td
(of)Tj
1.0276 0 Td
(basal)Tj
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(keratinocy)Tj
4.2449 0 Td
(tes)Tj
1.3252 0 Td
(in)Tj
1.0489 0 Td
(adult)Tj
2.2748 0 Td
(human)Tj
3.0969 0 Td
(body)Tj
6.4984 0 Td
(Calculated)Tj
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(in)Tj
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(this)Tj
-5.5276 -1.1905 Td
(study)Tj
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(\(36x10)Tj
ET
Q
q
1 j
1 J
0 w
5.9998 0 0 5.3325 221.7826 436.9322 cm
BT
/F6 1 Tf
1 TL
0 0 Td
(9)Tj
ET
Q
q
1 j
1 J
0 w
7.9999 0 0 7.9999 224.6173 433.4173 cm
BT
/F6 1 Tf
1 TL
0 0 Td
(1\))Tj
-3.0756 -1.1905 Td
(mitoses)Tj
8.1496 1.1905 Td
(Number)Tj
3.6213 0 Td
(of)Tj
1.0346 0 Td
(mitoses)Tj
3.2812 0 Td
(needed)Tj
3.1181 0 Td
(to)Tj
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(obtain)Tj
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(total)Tj
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(number)Tj
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(basal)Tj
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(keratino)Tj
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(cytes)Tj
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(in)Tj
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(this)Tj
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(study)Tj
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(35.1)Tj
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(generati)Tj
3.2456 0 Td
(ons)Tj
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3.6213 0 Td
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(generati)Tj
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(ons)Tj
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(of)Tj
1.0276 0 Td
(cells)Tj
1.9417 0 Td
(needed)Tj
3.1182 0 Td
(to)Tj
1.0417 0 Td
(obtain)Tj
2.7992 0 Td
(total)Tj
2.0268 0 Td
(number)Tj
3.4442 0 Td
(of)Tj
1.0275 0 Td
(basal)Tj
-25.9868 -1.1834 Td
(keratinocy)Tj
4.2449 0 Td
(tes)Tj
26.4616 1.1834 Td
(Calculated)Tj
4.4788 0 Td
(in)Tj
1.0488 0 Td
(this)Tj
-5.5276 -1.1834 Td
(study)Tj
-38.8561 -1.5662 Td
(1x10)Tj
ET
Q
q
1 j
1 J
0 w
5.9998 0 0 5.3325 215.2062 392.9385 cm
BT
/F6 1 Tf
1 TL
0 0 Td
(-9)Tj
ET
Q
q
1 j
1 J
0 w
7.9999 0 0 7.9999 265.2094 389.3669 cm
BT
/F6 1 Tf
1 TL
0 0 Td
(Approxim)Tj
4.1598 0 Td
(ate)Tj
1.3961 0 Td
(per)Tj
1.552 0 Td
(nucleotid)Tj
3.7843 0 Td
(e)Tj
0.659 0 Td
(point)Tj
2.3811 0 Td
(mutation)Tj
3.9473 0 Td
(rate)Tj
1.7646 0 Td
(per)Tj
1.552 0 Td
(mitosis)Tj
9.5103 0 Td
([)Tj
0.83 0.64 0.02 0 k
(26)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(28)Tj
0 g
(])Tj
-38.8561 -1.559 Td
(6x10)Tj
ET
Q
q
1 j
1 J
0 w
5.9998 0 0 5.3325 215.2062 380.4661 cm
BT
/F6 1 Tf
1 TL
0 0 Td
(9)Tj
ET
Q
q
1 j
1 J
0 w
7.9999 0 0 7.9999 219.9118 376.8944 cm
BT
/F6 1 Tf
1 TL
0 0 Td
(nucleotides)Tj
5.6622 0 Td
(Approxim)Tj
4.1599 0 Td
(ate)Tj
1.396 0 Td
(number)Tj
3.4371 0 Td
(of)Tj
1.0276 0 Td
(nucleotides)Tj
4.8118 0 Td
(per)Tj
1.552 0 Td
(genome)Tj
14.3221 0 Td
([)Tj
0.83 0.64 0.02 0 k
(34)Tj
0 g
(])Tj
-38.8561 -1.5661 Td
(6)Tj
0.7087 0 Td
(mutation)Tj
3.7133 0 Td
(s)Tj
3.7276 0 Td
(Expected)Tj
3.8977 0 Td
(numb)Tj
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(er)Tj
1.0347 0 Td
(of)Tj
1.0276 0 Td
(novel)Tj
2.4236 0 Td
(point)Tj
2.374 0 Td
(mutations)Tj
4.3158 0 Td
(per)Tj
1.5449 0 Td
(mitosis)Tj
11.6859 0 Td
(Calculated)Tj
4.4788 0 Td
(in)Tj
1.0488 0 Td
(this)Tj
-5.5276 -1.1835 Td
(study)Tj
-38.8561 -1.5661 Td
(216x10)Tj
ET
Q
q
1 j
1 J
0 w
5.9998 0 0 5.3325 222.8598 345.9401 cm
BT
/F6 1 Tf
1 TL
0 0 Td
(9)Tj
ET
Q
q
1 j
1 J
0 w
7.9999 0 0 7.9999 200.0125 332.9007 cm
BT
/F6 1 Tf
1 TL
0 0 Td
(mutation)Tj
3.7134 0 Td
(s)Tj
4.4362 1.1834 Td
(Expected)Tj
3.8977 0 Td
(numb)Tj
2.4024 0 Td
(er)Tj
1.0346 0 Td
(of)Tj
1.0276 0 Td
(point)Tj
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(mutation)Tj
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(s)Tj
0.5953 0 Td
(in)Tj
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(basal)Tj
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(keratinocy)Tj
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(tes)Tj
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(of)Tj
1.0275 0 Td
(human)Tj
-24.9238 -1.1834 Td
(body)Tj
2.2323 0 Td
(at)Tj
0.9709 0 Td
(adulthood)Tj
27.5034 1.1834 Td
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4.4787 0 Td
(in)Tj
1.0489 0 Td
(this)Tj
-5.5276 -1.1834 Td
(study)Tj
-38.8562 -1.6299 Td
(36x)Tj
8.1496 0 Td
(Average)Tj
3.5008 0 Td
(point)Tj
2.3812 0 Td
(mutation)Tj
3.9472 0 Td
(frequency)Tj
4.2166 0 Td
(of)Tj
1.0276 0 Td
(each)Tj
2.048 0 Td
(nucleotide)Tj
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(in)Tj
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(basal)Tj
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(keratinocy)Tj
4.2449 0 Td
(tes)Tj
1.3182 0 Td
(of)Tj
1.0346 0 Td
(human)Tj
3.0969 0 Td
(body)Tj
2.2323 0 Td
(at)Tj
0.9638 0 Td
(adulthood)Tj
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(in)Tj
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(this)Tj
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(study)Tj
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(105)Tj
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(number)Tj
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(of)Tj
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(somatic)Tj
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(mutation)Tj
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(s)Tj
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(expected)Tj
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(to)Tj
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(have)Tj
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(accumulate)Tj
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(d)Tj
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(adulthood)Tj
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(in)Tj
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(this)Tj
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(study)Tj
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(6)Tj
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(nucleotid)Tj
3.7843 0 Td
(es)Tj
3.6567 0 Td
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(target)Tj
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(nucleotides)Tj
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(a)Tj
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(reverse)Tj
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(mutation)Tj
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(in)Tj
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(REB)Tj
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(patients)Tj
3.4016 0 Td
(with)Tj
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(2)Tj
0.7087 0 Td
(nonsense)Tj
3.9685 0 Td
(mutation)Tj
3.7134 0 Td
(s)Tj
22.316 1.1906 Td
(Calculated)Tj
4.4787 0 Td
(in)Tj
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(this)Tj
-5.5276 -1.1906 Td
(study)Tj
-38.8562 -1.559 Td
(6x10)Tj
ET
Q
q
1 j
1 J
0 w
5.9998 0 0 5.3325 215.2062 256.9322 cm
BT
/F6 1 Tf
1 TL
0 0 Td
(-9)Tj
ET
Q
q
1 j
1 J
0 w
7.9999 0 0 7.9999 265.2094 253.3606 cm
BT
/F6 1 Tf
1 TL
0 0 Td
(Probability)Tj
4.6701 0 Td
(of)Tj
1.0346 0 Td
(a)Tj
0.6662 0 Td
(reverse)Tj
3.0756 0 Td
(point)Tj
2.374 0 Td
(mutation)Tj
3.9473 0 Td
(per)Tj
1.552 0 Td
(mitosis)Tj
13.3867 0 Td
(Calculated)Tj
4.4788 0 Td
(in)Tj
1.0488 0 Td
(this)Tj
-5.5276 -1.1905 Td
(study)Tj
-38.8561 -1.5591 Td
(1.6x10)Tj
ET
Q
q
1 j
1 J
0 w
5.9998 0 0 5.3325 220.8755 234.9354 cm
BT
/F6 1 Tf
1 TL
0 0 Td
(-94)Tj
ET
Q
q
1 j
1 J
0 w
7.9999 0 0 7.9999 265.2094 231.3637 cm
BT
/F6 1 Tf
1 TL
0 0 Td
(Probability)Tj
4.6701 0 Td
(that)Tj
1.8 0 Td
(no)Tj
1.2898 0 Td
(reverse)Tj
3.0756 0 Td
(mutation)Tj
3.9472 0 Td
(occurs)Tj
2.856 0 Td
(during)Tj
2.9551 0 Td
(total)Tj
2.0197 0 Td
(\(36x10)Tj
ET
Q
q
1 j
1 J
0 w
5.9998 0 0 5.3325 467.8866 234.9354 cm
BT
/F6 1 Tf
1 TL
0 0 Td
(9)Tj
ET
Q
q
1 j
1 J
0 w
7.9999 0 0 7.9999 470.7779 231.3637 cm
BT
/F6 1 Tf
1 TL
0 0 Td
(1\))Tj
-25.6962 -1.1905 Td
(mitoses)Tj
3.2811 0 Td
(\()Tj
/F11 1 Tf
[()]TJ
ET
Q
q
1 j
1 J
0 w
5.9998 0 0 5.3325 298.6015 220.5354 cm
BT
/F11 1 Tf
1 TL
0 0 Td
[()6()12()]TJ
ET
Q
q
1 j
1 J
0 w
7.9999 0 0 7.9999 306.4251 221.8393 cm
BT
/F6 1 Tf
1 TL
0 0 Td
(\))Tj
25.5545 1.1905 Td
(Calculated)Tj
4.4788 0 Td
(in)Tj
1.0488 0 Td
(this)Tj
-5.5276 -1.1905 Td
(study)Tj
-38.8561 -1.559 Td
(~1)Tj
8.1496 0 Td
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(that)Tj
1.7999 0 Td
(at)Tj
0.9708 0 Td
(least)Tj
2.0056 0 Td
(one)Tj
1.7149 0 Td
(reverse)Tj
3.0757 0 Td
(mutatio)Tj
3.1606 0 Td
(n)Tj
0.7866 0 Td
(occurs)Tj
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(during)Tj
2.948 0 Td
(total)Tj
2.0268 0 Td
(number)Tj
-26.0151 -1.1906 Td
(of)Tj
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(mitoses)Tj
3.2811 0 Td
(\()Tj
/F11 1 Tf
[()]TJ
/F6 1 Tf
1.1267 0 Td
(=)Tj
0.8079 0 Td
(1)Tj
0.7087 0 Td
()Tj
/F11 1 Tf
[()]TJ
ET
Q
q
1 j
1 J
0 w
5.9998 0 0 5.3325 329.3858 198.5385 cm
BT
/F11 1 Tf
1 TL
0 0 Td
[()6()12()]TJ
ET
Q
q
1 j
1 J
0 w
7.9999 0 0 7.9999 337.2094 199.8425 cm
BT
/F6 1 Tf
1 TL
0 0 Td
(\))Tj
21.7064 1.1905 Td
(Calculated)Tj
4.4788 0 Td
(in)Tj
1.0488 0 Td
(this)Tj
-5.5276 -1.1905 Td
(study)Tj
-38.8561 -1.559 Td
(216)Tj
1.6583 0 Td
(mutations)Tj
6.4914 0 Td
(Expected)Tj
3.8976 0 Td
(numb)Tj
2.4024 0 Td
(er)Tj
1.0347 0 Td
(of)Tj
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(reverse)Tj
3.0756 0 Td
(point)Tj
2.3811 0 Td
(mutation)Tj
3.7134 0 Td
(s)Tj
0.5953 0 Td
(during)Tj
2.948 0 Td
(\(36x10)Tj
ET
Q
q
1 j
1 J
0 w
5.9998 0 0 5.3325 455.5842 190.885 cm
BT
/F6 1 Tf
1 TL
0 0 Td
(9)Tj
ET
Q
q
1 j
1 J
0 w
7.9999 0 0 7.9999 458.4755 187.37 cm
BT
/F6 1 Tf
1 TL
0 0 Td
(1\))Tj
1.5661 0 Td
(mitoses)Tj
4.9819 0 Td
(Calculated)Tj
4.4788 0 Td
(in)Tj
1.0488 0 Td
(this)Tj
-5.5276 -1.1905 Td
(study)Tj
-38.8561 -1.5591 Td
(100)Tj
1.6583 0 Td
(mm)Tj
ET
Q
q
1 j
1 J
0 w
5.9998 0 0 5.3325 226.4314 168.8881 cm
BT
/F6 1 Tf
1 TL
0 0 Td
(2)Tj
ET
Q
q
1 j
1 J
0 w
7.9999 0 0 7.9999 265.2094 165.3732 cm
BT
/F6 1 Tf
1 TL
0 0 Td
(Minimal)Tj
3.7205 0 Td
(size)Tj
1.7008 0 Td
(of)Tj
1.0275 0 Td
(revertant)Tj
3.8764 0 Td
(patch)Tj
2.4449 0 Td
(to)Tj
1.0347 0 Td
(be)Tj
1.1693 0 Td
(clinically)Tj
3.8126 0 Td
(recogniza)Tj
3.8693 0 Td
(ble)Tj
8.0505 0 Td
([)Tj
0.83 0.64 0.02 0 k
(9)Tj
0 g
(],)Tj
0.83 0.64 0.02 0 k
1.6228 0 Td
(Fig)Tj
1.4953 0 Td
(1)Tj
0 g
-41.9742 -1.5661 Td
(2x10)Tj
ET
Q
q
1 j
1 J
0 w
5.9998 0 0 5.3325 215.2062 156.4157 cm
BT
/F6 1 Tf
1 TL
0 0 Td
(6)Tj
ET
Q
q
1 j
1 J
0 w
7.9999 0 0 7.9999 219.9118 152.844 cm
BT
/F6 1 Tf
1 TL
0 0 Td
(cells)Tj
5.6622 0 Td
(Number)Tj
3.6213 0 Td
(of)Tj
1.0346 0 Td
(basal)Tj
2.2253 0 Td
(keratin)Tj
2.8488 0 Td
(ocytes)Tj
2.7142 0 Td
(required)Tj
3.6709 0 Td
(for)Tj
1.4031 0 Td
(a)Tj
0.6662 0 Td
(revertan)Tj
3.3378 0 Td
(t)Tj
0.5315 0 Td
(patch)Tj
8.6528 0 Td
(Calculated)Tj
4.4788 0 Td
(in)Tj
1.0488 0 Td
(this)Tj
-5.5276 -1.1834 Td
(study)Tj
-38.8561 -1.5662 Td
(21)Tj
1.1835 0 Td
(generatio)Tj
3.7558 0 Td
(ns)Tj
3.2103 0 Td
(Number)Tj
3.6213 0 Td
(of)Tj
1.0346 0 Td
(generati)Tj
3.2457 0 Td
(ons)Tj
1.6583 0 Td
(needed)Tj
3.1111 0 Td
(to)Tj
1.0417 0 Td
(obtain)Tj
2.8063 0 Td
(2x10)Tj
ET
Q
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