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Hyun Ju In, Heeji Lim, Jung-Ah Lee, Sang-Rae Lee, Yeung Bae Jin, Kang-Jin Jeong, Ji-Yeon Hyeon, Jung Sik Yoo, June-Woo Lee, Young Ki Choi, Sang-Won Lee
Enhanced neutralizing antibody response induced by inactivated enterovirus 71 in cynomolgus monkeys
www.plosone.org
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2.8233 0 Td
(T-cell)Tj
2.4264 0 Td
(lymphotropic)Tj
5.4822 0 Td
(virus)Tj
2.126 0 Td
(\(STLV\),)Tj
3.3335 0 Td
(tuberculosis,)Tj
5.057 0 Td
(every)Tj
-34.6845 -1.2982 Td
(year.)Tj
2.0466 0 Td
(As)Tj
1.2358 0 Td
(all)Tj
1.0942 0 Td
(collections)Tj
4.2973 0 Td
(of)Tj
0.9865 0 Td
(blood)Tj
2.4321 0 Td
(samples)Tj
3.2711 0 Td
(and)Tj
1.6838 0 Td
(vaccine)Tj
3.0784 0 Td
(administration)Tj
5.9471 0 Td
(were)Tj
2.0579 0 Td
(performed)Tj
4.3256 0 Td
(under)Tj
2.5399 0 Td
(anes-)Tj
-34.9963 -1.2983 Td
(thesia,)Tj
2.6418 0 Td
(the)Tj
1.423 0 Td
(primates)Tj
3.583 0 Td
(were)Tj
2.0579 0 Td
(anesthetized)Tj
4.9776 0 Td
(by)Tj
1.1509 0 Td
(an)Tj
1.1678 0 Td
(intramuscular)Tj
5.641 0 Td
(injection)Tj
3.6169 0 Td
(of)Tj
0.9865 0 Td
(ketamine)Tj
3.8041 0 Td
(\(5mg)Tj
2.2563 0 Td
(/kg\))Tj
1.7858 0 Td
(into)Tj
-35.0926 -1.3039 Td
(the)Tj
1.4116 0 Td
(thigh)Tj
2.2167 0 Td
(muscle.)Tj
3.1237 0 Td
(Blood)Tj
2.5002 0 Td
(samples)Tj
3.2598 0 Td
(were)Tj
2.0466 0 Td
(collected)Tj
3.5886 0 Td
(from)Tj
2.1317 0 Td
(the)Tj
1.4116 0 Td
(femoral)Tj
3.1861 0 Td
(vein,)Tj
2.0523 0 Td
(and)Tj
1.6724 0 Td
(the)Tj
1.4117 0 Td
(vaccine)Tj
3.0727 0 Td
(was)Tj
1.6441 0 Td
(admin-)Tj
-34.7298 -1.2983 Td
(istered)Tj
2.7779 0 Td
(to)Tj
0.9921 0 Td
(arm)Tj
1.7972 0 Td
(muscle.)Tj
3.1351 0 Td
(A)Tj
0.89 0 Td
(humane)Tj
3.4073 0 Td
(euthanasia)Tj
4.3143 0 Td
(procedure)Tj
4.1669 0 Td
(was)Tj
1.6554 0 Td
(performed)Tj
4.3256 0 Td
(by)Tj
1.1452 0 Td
(injecting)Tj
3.5773 0 Td
(pentobarbital)Tj
-32.1843 -1.2982 Td
(\(100)Tj
1.9218 0 Td
(mg/kg\))Tj
3.0387 0 Td
(intravenously)Tj
5.4539 0 Td
(under)Tj
2.5398 0 Td
(the)Tj
1.423 0 Td
(recommendation)Tj
6.9165 0 Td
(of)Tj
0.9808 0 Td
(the)Tj
1.4229 0 Td
(certified)Tj
3.3676 0 Td
(veterinarian,)Tj
5.0796 0 Td
(if)Tj
0.7427 0 Td
(the)Tj
1.423 0 Td
(animal)Tj
-34.3103 -1.2983 Td
(was)Tj
1.6497 0 Td
(diagnosed)Tj
4.1386 0 Td
(with)Tj
1.9332 0 Td
(certain)Tj
2.8743 0 Td
(diseases)Tj
3.2485 0 Td
(such)Tj
1.9956 0 Td
(as)Tj
0.9864 0 Td
(unknown)Tj
3.9685 0 Td
(fever,)Tj
2.3074 0 Td
(and)Tj
1.6837 0 Td
(severe)Tj
2.5852 0 Td
(diarrhea)Tj
3.4469 0 Td
(\(containing)Tj
-30.818 -1.3039 Td
(blood,)Tj
2.6418 0 Td
(mucus,)Tj
3.0104 0 Td
(and)Tj
1.6838 0 Td
(pus\),)Tj
2.1089 0 Td
(was)Tj
1.6498 0 Td
(moribund,)Tj
4.3823 0 Td
(or)Tj
1.0658 0 Td
(was)Tj
1.6498 0 Td
(not)Tj
1.525 0 Td
(eating/drinking)Tj
6.2362 0 Td
(and)Tj
1.6838 0 Td
(did)Tj
1.4967 0 Td
(not)Tj
1.525 0 Td
(show)Tj
2.2337 0 Td
(improve-)Tj
-32.893 -1.2983 Td
(ment)Tj
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(following)Tj
3.8381 0 Td
(medication)Tj
4.5751 0 Td
(or)Tj
1.0658 0 Td
(environmental)Tj
5.9017 0 Td
(enrichment.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 433.9275 cm
BT
/F12 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Production)Tj
4.9606 0 Td
(of)Tj
1.0677 0 Td
(inactivated)Tj
4.8379 0 Td
(EV71)Tj
2.4945 0 Td
(vaccines)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 416.9196 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(The)Tj
1.7801 0 Td
(KCDC-HFMDV1-EV7)Tj
9.2749 0 Td
(1)Tj
0.6916 0 Td
(vaccine)Tj
3.1975 0 Td
(strain)Tj
2.5001 0 Td
(\(C4a)Tj
2.1317 0 Td
(subgenotype\))Tj
5.5955 0 Td
(was)Tj
1.6952 0 Td
(isolated)Tj
3.2881 0 Td
(from)Tj
2.2054 0 Td
(a)Tj
0.6519 0 Td
(patient)Tj
-33.012 -1.2982 Td
(with)Tj
1.9955 0 Td
(HFMD)Tj
3.1465 0 Td
(in)Tj
1.0318 0 Td
(Korea)Tj
2.6305 0 Td
(in)Tj
1.0375 0 Td
(2012.)Tj
2.347 0 Td
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1.7802 0 Td
(strain)Tj
2.5001 0 Td
(was)Tj
1.7008 0 Td
(propagated,)Tj
4.9436 0 Td
(and)Tj
1.7291 0 Td
(viral)Tj
1.9899 0 Td
(titers)Tj
2.2451 0 Td
(were)Tj
2.1203 0 Td
(evaluated)Tj
3.9911 0 Td
(in)Tj
-35.189 -1.2983 Td
(Vero)Tj
2.2166 0 Td
(cells)Tj
1.9162 0 Td
(\(green)Tj
2.795 0 Td
(monkey)Tj
3.4696 0 Td
(kidney)Tj
2.9366 0 Td
(cells\))Tj
2.2621 0 Td
(using)Tj
2.3924 0 Td
(Dulbecco's)Tj
4.5864 0 Td
(modified)Tj
3.8495 0 Td
(Eagle)Tj
2.3584 0 Td
(medium)Tj
3.6056 0 Td
(\(DMEM\).)Tj
-32.3884 -1.3039 Td
(Viral)Tj
2.2336 0 Td
(titers)Tj
2.2394 0 Td
(were)Tj
2.1203 0 Td
(determined)Tj
4.8529 0 Td
(by)Tj
1.1792 0 Td
(microtitration)Tj
5.9017 0 Td
(using)Tj
2.3867 0 Td
(Vero)Tj
2.2167 0 Td
(cells)Tj
1.9219 0 Td
(and)Tj
1.7291 0 Td
(expressed)Tj
4.0932 0 Td
(as)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(50%)Tj
1.9332 0 Td
(tissue)Tj
-35.2911 -1.2983 Td
(culture)Tj
3.0387 0 Td
(infective)Tj
3.6113 0 Td
(dose)Tj
2.0409 0 Td
(\(TCID)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 313.8519 363.2881 cm
BT
/F7 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(50)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 320.9385 364.9322 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(\),)Tj
0.788 0 Td
(according)Tj
4.1839 0 Td
(to)Tj
1.0261 0 Td
(the)Tj
1.4684 0 Td
(Reed-Muench)Tj
5.913 0 Td
(method.)Tj
3.5489 0 Td
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1.7802 0 Td
(vaccine)Tj
3.1975 0 Td
(strain)Tj
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1.6951 0 Td
(inactivated)Tj
4.5978 0 Td
(using)Tj
2.3924 0 Td
(formaldehyde)Tj
5.7712 0 Td
(\(Sigma-Aldrich,)Tj
6.6444 0 Td
(St.)Tj
1.2189 0 Td
(Louis,)Tj
2.6475 0 Td
(MO,)Tj
2.0806 0 Td
(USA\))Tj
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(at)Tj
0.9524 0 Td
(37C)Tj
2.2224 0 Td
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1.389 0 Td
(5)Tj
0.6973 0 Td
(days)Tj
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(and)Tj
1.7292 0 Td
(mixed)Tj
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(with)Tj
2.0012 0 Td
(an)Tj
1.2019 0 Td
(equal)Tj
2.3584 0 Td
(volume)Tj
3.1974 0 Td
(of)Tj
1.0148 0 Td
(aluminum)Tj
4.4107 0 Td
(hydroxide)Tj
4.2916 0 Td
(\(InvivoGen,)Tj
5.0456 0 Td
(San)Tj
1.6781 0 Td
(Diego,)Tj
2.846 0 Td
(CA,)Tj
1.7915 0 Td
(USA\),)Tj
-34.2876 -1.2983 Td
(which)Tj
2.6476 0 Td
(is)Tj
0.8504 0 Td
(the)Tj
1.4683 0 Td
(most)Tj
2.2053 0 Td
(commonly)Tj
4.5468 0 Td
(used)Tj
2.0578 0 Td
(adjuvant)Tj
3.702 0 Td
(in)Tj
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(human)Tj
3.0784 0 Td
(vaccines.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 299.4519 cm
BT
/F12 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Immunization)Tj
6.2787 0 Td
(of)Tj
1.0678 0 Td
(monkeys)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 282.444 cm
BT
/F7 1 Tf
1 TL
-0.02 Tc
0 0 Td
(Five)Tj
1.8255 0 Td
(cynomolgus)Tj
4.9209 0 Td
(monkeys)Tj
3.719 0 Td
(\()Tj
/F8 1 Tf
[()28(\r)6()7(\r)6()7(\r)]TJ
3.5206 0 Td
[()9(\r\n)-3()1()4()1( )4()4(\r)16()-9()-4(\n)]TJ
/F7 1 Tf
(\),)Tj
4.8642 0 Td
(3)Tj
0.6803 0 Td
(years)Tj
2.1827 0 Td
(of)Tj
0.9808 0 Td
(age)Tj
1.4967 0 Td
(\(body)Tj
2.4774 0 Td
(weight)Tj
2.7893 0 Td
(of)Tj
0.9808 0 Td
(2.883.33)Tj
3.9004 0 Td
(kg\),)Tj
-34.3386 -1.2982 Td
(were)Tj
2.0579 0 Td
(randomly)Tj
4.0025 0 Td
(allocated)Tj
3.617 0 Td
(into)Tj
1.7744 0 Td
(two)Tj
1.6611 0 Td
(groups)Tj
2.8744 0 Td
(\(G1)Tj
1.7007 0 Td
(and)Tj
1.6838 0 Td
(G2\);)Tj
1.9105 0 Td
(monkeys)Tj
3.7191 0 Td
(in)Tj
1.0034 0 Td
(the)Tj
1.423 0 Td
(G1)Tj
1.3833 0 Td
(group)Tj
2.5285 0 Td
(\(n)Tj
1.0715 0 Td
(=)Tj
0.788 0 Td
(3\))Tj
1.0035 0 Td
(and)Tj
1.6837 0 Td
(G2)Tj
-35.8863 -1.2983 Td
(group)Tj
2.5284 0 Td
(\(n)Tj
1.0715 0 Td
(=)Tj
0.7881 0 Td
(2\))Tj
1.0034 0 Td
(were)Tj
2.058 0 Td
(intramuscularly)Tj
6.3098 0 Td
(administrated)Tj
5.5899 0 Td
(with)Tj
1.9332 0 Td
(0.5ml)Tj
2.3811 0 Td
(of)Tj
0.9808 0 Td
(20)Tj
/F13 1 Tf
1.1395 0 Td
[()]TJ
/F7 1 Tf
(g)Tj
1.1566 0 Td
(of)Tj
0.9864 0 Td
(inactivated)Tj
4.4164 0 Td
(EV71)Tj
2.3754 0 Td
(vaccine)Tj
-34.7185 -1.3039 Td
(mixed)Tj
2.6418 0 Td
(with)Tj
1.9332 0 Td
(2.5)Tj
1.3493 0 Td
(mg)Tj
1.474 0 Td
(alum)Tj
2.1827 0 Td
(or)Tj
1.0658 0 Td
(phosphate-buffered)Tj
7.7556 0 Td
(saline)Tj
2.4037 0 Td
(\(PBS\),)Tj
2.6419 0 Td
(respectively.)Tj
4.9039 0 Td
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1.7348 0 Td
(monkeys)Tj
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(in)Tj
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-34.8092 -1.2983 Td
(group)Tj
2.5284 0 Td
(were)Tj
2.058 0 Td
(boost)Tj
2.3187 0 Td
(vaccinated)Tj
4.2973 0 Td
(at)Tj
0.9184 0 Td
(4)Tj
0.6803 0 Td
(or)Tj
1.0658 0 Td
(8)Tj
0.6804 0 Td
(weeks)Tj
2.5284 0 Td
(after)Tj
1.9559 0 Td
(primary)Tj
3.3449 0 Td
(vaccination,)Tj
4.8586 0 Td
(using)Tj
2.3073 0 Td
(the)Tj
1.423 0 Td
(same)Tj
2.194 0 Td
(vaccine.)Tj
-33.1594 -1.2982 Td
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1.3492 0 Td
(animals)Tj
3.2145 0 Td
(were)Tj
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(provided)Tj
3.6907 0 Td
(by)Tj
1.1509 0 Td
(the)Tj
1.423 0 Td
(National)Tj
3.5603 0 Td
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3.2825 0 Td
(Research)Tj
3.6793 0 Td
(Center)Tj
2.8516 0 Td
(\(NPRC\))Tj
3.3846 0 Td
(of)Tj
0.9808 0 Td
(Korea.)Tj
2.7609 0 Td
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-33.3862 -1.2983 Td
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(and)Tj
1.6838 0 Td
(temperature)Tj
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(of)Tj
0.9864 0 Td
(monkeys)Tj
3.719 0 Td
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2.058 0 Td
(measured)Tj
3.9798 0 Td
(individually)Tj
4.7962 0 Td
(and)Tj
1.6838 0 Td
(recorded.)Tj
3.8777 0 Td
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2.5058 0 Td
(samples)Tj
-33.029 -1.3039 Td
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2.0579 0 Td
(collected)Tj
3.5943 0 Td
(\(12)Tj
1.9672 0 Td
(ml\))Tj
1.5761 0 Td
(at)Tj
0.9184 0 Td
(0,)Tj
0.8901 0 Td
(3,)Tj
0.89 0 Td
(7,)Tj
0.8901 0 Td
(12,)Tj
1.3493 0 Td
(28,)Tj
1.3493 0 Td
(and)Tj
1.6781 0 Td
(54)Tj
1.1395 0 Td
(weeks)Tj
2.5285 0 Td
(after)Tj
1.9559 0 Td
(vaccination.)Tj
4.8585 0 Td
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5.8507 0 Td
(analyses)Tj
-33.4939 -1.2983 Td
(were)Tj
2.0579 0 Td
(conducted)Tj
4.2803 0 Td
(using)Tj
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(an)Tj
1.1679 0 Td
(automated)Tj
4.3483 0 Td
(hematology)Tj
4.7452 0 Td
(analyzer)Tj
3.4129 0 Td
(\(CELL_DYN)Tj
5.3291 0 Td
(3700;)Tj
2.2677 0 Td
(Abbott,)Tj
3.1351 0 Td
(IL,)Tj
1.2756 0 Td
(USA\))Tj
-34.333 -1.2982 Td
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(to)Tj
0.9921 0 Td
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1.423 0 Td
(manufacturer's)Tj
6.0378 0 Td
(instructions.)Tj
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(experiments)Tj
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-34.0438 -1.304 Td
(accordance)Tj
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(with)Tj
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(the)Tj
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4.3654 0 Td
(of)Tj
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(the)Tj
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4.955 0 Td
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3.1237 0 Td
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2.0523 0 Td
(and)Tj
1.6781 0 Td
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(Committee)Tj
4.5978 0 Td
(\(KRIB-)Tj
-32.8023 -1.2982 Td
(B-AEC-14126\))Tj
5.9413 0 Td
(in)Tj
1.0035 0 Td
(the)Tj
1.423 0 Td
(Korea)Tj
2.5511 0 Td
(Research)Tj
3.6794 0 Td
(Institute)Tj
3.4356 0 Td
(of)Tj
0.9864 0 Td
(Bioscience)Tj
4.2803 0 Td
(and)Tj
1.6838 0 Td
(Biotechnology)Tj
5.7656 0 Td
(\(KRIBB\).)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 112.9889 cm
BT
/F12 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Serum)Tj
2.9386 0 Td
(neutralizing)Tj
5.3102 0 Td
(assay)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 95.9811 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(The)Tj
1.7801 0 Td
(serum)Tj
2.7269 0 Td
(neutralizing)Tj
5.0286 0 Td
(\(SN\))Tj
2.109 0 Td
(assay)Tj
2.2677 0 Td
(was)Tj
1.7008 0 Td
(conducted)Tj
4.4277 0 Td
(in)Tj
1.0318 0 Td
(96-well)Tj
3.1237 0 Td
(microplates)Tj
4.8869 0 Td
(containing)Tj
4.5298 0 Td
(confluent)Tj
-33.613 -1.2982 Td
(Vero)Tj
2.2166 0 Td
(cells)Tj
1.9162 0 Td
(that)Tj
1.7802 0 Td
(were)Tj
2.126 0 Td
(seeded)Tj
2.9026 0 Td
(24)Tj
1.1735 0 Td
(h)Tj
0.7484 0 Td
(before)Tj
2.7382 0 Td
(the)Tj
1.4684 0 Td
(experiment.)Tj
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1.7802 0 Td
(monkey)Tj
3.4696 0 Td
(sera)Tj
1.8141 0 Td
(were)Tj
2.1203 0 Td
(inactivated)Tj
4.5978 0 Td
(at)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I1 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 377.1212 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Enterovirus)Tj
5.1945 0 Td
(71)Tj
1.311 0 Td
(inactivate)Tj
4.1386 0 Td
(d)Tj
0.7654 0 Td
(vaccine)Tj
3.5504 0 Td
(in)Tj
0.978 0 Td
(cynomolgus)Tj
5.4709 0 Td
(monkey)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
81.5811 34.9228 m
237.8835 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
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