%PDF-1.6
%
1 0 obj
<>
endobj
2 0 obj
<>stream
Beatrice Mao, Cynthia F. Moss, Gerald S. Wilkinson
Age-dependent gene expression in the inner ear of big brown bats (Eptesicus fuscus)
www.plosone.org
www.plosone.org
endstream
endobj
3 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 12 0 R/Annots 13 0 R/Contents 14 0 R/TrimBox[0 0 612 792]>>
endobj
13 0 obj
[15 0 R 16 0 R 17 0 R 18 0 R 19 0 R 20 0 R 21 0 R 22 0 R 23 0 R 24 0 R 25 0 R 26 0 R 27 0 R 28 0 R 29 0 R 30 0 R 31 0 R 32 0 R 33 0 R 34 0 R 35 0 R 36 0 R 37 0 R 38 0 R 39 0 R 40 0 R]
endobj
15 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186667.ref010)>>
endobj
16 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186667.ref011)>>
endobj
17 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186667.ref017)>>
endobj
18 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186667.ref018)>>
endobj
19 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186667.ref019)>>
endobj
20 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186667.ref020)>>
endobj
21 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186667.ref021)>>
endobj
22 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186667.ref022)>>
endobj
23 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186667.ref023)>>
endobj
24 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186667.ref028)>>
endobj
25 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186667.ref026)>>
endobj
26 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186667.ref029)>>
endobj
27 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186667.ref030)>>
endobj
28 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186667.ref031)>>
endobj
29 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186667.ref032)>>
endobj
30 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186667.ref033)>>
endobj
31 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186667.ref034)>>
endobj
32 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186667.ref035)>>
endobj
33 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186667.ref036)>>
endobj
34 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186667.ref037)>>
endobj
35 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186667.ref026)>>
endobj
36 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186667.ref029)>>
endobj
37 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186667.ref024)>>
endobj
38 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186667.ref038)>>
endobj
39 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186667.ref039)>>
endobj
40 0 obj
<>/Border[0 0 0]/A 41 0 R>>
endobj
41 0 obj
<>
endobj
14 0 obj
[42 0 R 43 0 R 44 0 R 45 0 R 46 0 R 47 0 R 48 0 R 49 0 R 50 0 R 51 0 R 52 0 R 53 0 R 54 0 R 55 0 R 56 0 R 57 0 R 58 0 R 59 0 R 60 0 R 61 0 R 62 0 R 63 0 R 64 0 R 65 0 R 66 0 R 67 0 R]
endobj
42 0 obj
<>stream
q
0.83 0.64 0.02 0 k
433.1339 693.2976 m
442.6583 693.2976 l
h
f*
203.4142 602.3055 m
212.9386 602.3055 l
h
f*
218.0976 602.3055 m
227.622 602.3055 l
h
f*
434.7213 550.3181 m
444.2457 550.3181 l
h
f*
328.4787 537.3354 m
338.0031 537.3354 l
h
f*
338.4 511.3134 m
347.9244 511.3134 l
h
f*
418.9039 498.3307 m
428.4283 498.3307 l
h
f*
433.5874 498.3307 m
443.1118 498.3307 l
h
f*
354.6142 459.326 m
364.0819 459.326 l
h
f*
369.2976 459.326 m
378.7654 459.326 l
h
f*
338.0031 433.3039 m
347.4709 433.3039 l
h
f*
352.6866 433.3039 m
362.1543 433.3039 l
h
f*
480.6425 407.3386 m
490.1669 407.3386 l
h
f*
494.589 407.3386 m
504.1134 407.3386 l
h
f*
358.9795 368.3339 m
368.5039 368.3339 l
h
f*
235.4457 316.3465 m
244.9701 316.3465 l
h
f*
236.6362 303.3071 m
246.1039 303.3071 l
h
f*
533.1402 290.3244 m
542.6079 290.3244 l
h
f*
364.8756 277.3417 m
374.3433 277.3417 l
h
f*
338.0031 251.3197 m
347.5276 251.3197 l
h
f*
510.2929 212.315 m
519.8173 212.315 l
h
f*
524.9764 212.315 m
534.5008 212.315 l
h
f*
406.148 186.3496 m
415.6157 186.3496 l
h
f*
420.0945 186.3496 m
429.6189 186.3496 l
h
f*
434.0409 186.3496 m
443.5654 186.3496 l
h
f*
0 g
1 j
1 J
0 w
10 0 0 10 200.0125 707.4141 cm
BT
/F9 1 Tf
1 TL
-0.004 Tc
0 0 Td
(stands)Tj
2.7495 0 Td
(in)Tj
1.0375 0 Td
(contrast)Tj
3.4583 0 Td
(with)Tj
2.0012 0 Td
(the)Tj
1.4683 0 Td
(occurrence)Tj
4.6602 0 Td
(of)Tj
1.0148 0 Td
(age-related)Tj
4.6204 0 Td
(hearing)Tj
3.2598 0 Td
(loss)Tj
1.6895 0 Td
(\(presbycusis\))Tj
5.4765 0 Td
(in)Tj
1.0374 0 Td
(humans,)Tj
-32.4734 -1.3039 Td
(which)Tj
2.6475 0 Td
(has)Tj
1.542 0 Td
(been)Tj
2.126 0 Td
(estimated)Tj
4.0705 0 Td
(to)Tj
1.0262 0 Td
(be)Tj
1.1508 0 Td
(40%)Tj
1.9276 0 Td
(among)Tj
2.9933 0 Td
(those)Tj
2.3414 0 Td
(over)Tj
1.9729 0 Td
(70)Tj
1.1736 0 Td
([)Tj
0.83 0.64 0.02 0 k
(10)Tj
0 g
(].)Tj
-21.7756 -1.2982 Td
(The)Tj
1.7858 0 Td
(importance)Tj
4.8302 0 Td
(of)Tj
1.0148 0 Td
(hearing)Tj
3.2541 0 Td
(to)Tj
1.0262 0 Td
(echolocators)Tj
5.2497 0 Td
(has)Tj
1.542 0 Td
(been)Tj
2.126 0 Td
(illustrated)Tj
4.2179 0 Td
(by)Tj
1.1849 0 Td
(a)Tj
0.652 0 Td
(number)Tj
3.4185 0 Td
(of)Tj
1.0148 0 Td
(recent)Tj
2.7099 0 Td
(stud-)Tj
-35.223 -1.2983 Td
(ies)Tj
1.2699 0 Td
(examining)Tj
4.4617 0 Td
(the)Tj
1.4683 0 Td
(molecular)Tj
4.2179 0 Td
(evolution)Tj
4.0025 0 Td
(of)Tj
1.0148 0 Td
(genes)Tj
2.4378 0 Td
(involved)Tj
3.651 0 Td
(in)Tj
1.0375 0 Td
(hearing)Tj
3.2541 0 Td
(in)Tj
1.0375 0 Td
(bats.)Tj
2.0466 0 Td
(Several)Tj
3.0501 0 Td
(genes)Tj
-32.9497 -1.2983 Td
(known)Tj
3.0047 0 Td
(from)Tj
2.2053 0 Td
(human)Tj
3.0784 0 Td
(and)Tj
1.7291 0 Td
(mouse)Tj
2.8573 0 Td
(studies)Tj
2.9877 0 Td
(to)Tj
1.0262 0 Td
(be)Tj
1.1508 0 Td
(crucial)Tj
2.914 0 Td
(for)Tj
1.3833 0 Td
(normal)Tj
3.1465 0 Td
(hearing,)Tj
3.4865 0 Td
(such)Tj
2.058 0 Td
(as)Tj
1.0148 0 Td
(transmem-)Tj
-32.0426 -1.3039 Td
(brane)Tj
2.5058 0 Td
(channel-like)Tj
5.1533 0 Td
(1)Tj
0.6973 0 Td
(\()Tj
/F14 1 Tf
[()75()6()]TJ
/F9 1 Tf
(\))Tj
3.1011 0 Td
(and)Tj
/F14 1 Tf
1.7348 0 Td
[()2()20()8()9( )7(\n)12(\r)8()14()]TJ
/F9 1 Tf
(,)Tj
7.1263 0 Td
(exhibit)Tj
2.9763 0 Td
(convergence)Tj
5.2327 0 Td
(between)Tj
3.532 0 Td
(the)Tj
1.4683 0 Td
(two)Tj
1.7121 0 Td
(dis-)Tj
-35.24 -1.2982 Td
(tantly)Tj
2.5001 0 Td
(related)Tj
2.9423 0 Td
(groups)Tj
2.9707 0 Td
(of)Tj
1.0148 0 Td
(echolocating)Tj
5.2894 0 Td
(bats,)Tj
2.0466 0 Td
(or)Tj
1.0999 0 Td
(even)Tj
2.0693 0 Td
(between)Tj
3.5262 0 Td
(echolocating)Tj
5.2951 0 Td
(bats)Tj
1.8198 0 Td
(and)Tj
1.7292 0 Td
(whales,)Tj
3.1237 0 Td
(such)Tj
-35.4271 -1.2983 Td
(that)Tj
1.7744 0 Td
(gene)Tj
2.0863 0 Td
(trees)Tj
2.0976 0 Td
(sometimes)Tj
4.4958 0 Td
(group)Tj
2.6078 0 Td
(echolocators)Tj
5.2497 0 Td
(together)Tj
3.5377 0 Td
(to)Tj
1.0261 0 Td
(the)Tj
1.4683 0 Td
(exclusion)Tj
3.9912 0 Td
(of)Tj
1.0148 0 Td
(non-echolocators)Tj
-29.3497 -1.3039 Td
([)Tj
0.83 0.64 0.02 0 k
(11)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(17)Tj
0 g
(].)Tj
3.5432 0 Td
(While)Tj
2.6532 0 Td
(the)Tj
1.4684 0 Td
(results)Tj
2.8063 0 Td
(of)Tj
1.0148 0 Td
(these)Tj
2.2563 0 Td
(studies)Tj
2.9877 0 Td
(are)Tj
1.4457 0 Td
(compelling,)Tj
4.9096 0 Td
(the)Tj
1.4683 0 Td
(amount)Tj
3.3562 0 Td
(or)Tj
1.0998 0 Td
(timing)Tj
2.8857 0 Td
(of)Tj
1.0148 0 Td
(gene)Tj
-32.91 -1.2983 Td
(expression)Tj
4.4617 0 Td
(may)Tj
1.9332 0 Td
(also)Tj
1.7631 0 Td
(contribute)Tj
4.3937 0 Td
(to)Tj
1.0261 0 Td
(different)Tj
3.6567 0 Td
(phenotypes)Tj
4.7962 0 Td
(without)Tj
3.3335 0 Td
(requiring)Tj
3.9685 0 Td
(changes)Tj
3.4015 0 Td
(in)Tj
1.0375 0 Td
(coding)Tj
-33.7717 -1.2983 Td
(sequence.)Tj
4.0818 0 Td
(Recent)Tj
2.9594 0 Td
(studies)Tj
2.9877 0 Td
(have)Tj
2.0579 0 Td
(shown)Tj
2.8516 0 Td
(that)Tj
1.7745 0 Td
(changes)Tj
3.4072 0 Td
(in)Tj
1.0318 0 Td
(gene)Tj
2.0807 0 Td
(regulation)Tj
4.3086 0 Td
(can)Tj
1.6271 0 Td
(influence)Tj
3.9174 0 Td
(the)Tj
1.4684 0 Td
(physi-)Tj
-34.5541 -1.3039 Td
(cal)Tj
1.3209 0 Td
(differences)Tj
4.5694 0 Td
(between)Tj
3.5263 0 Td
(bats)Tj
1.8198 0 Td
(and)Tj
1.7291 0 Td
(other)Tj
2.3471 0 Td
(mammals:)Tj
4.3823 0 Td
(transgenic)Tj
4.3597 0 Td
(mice)Tj
2.1543 0 Td
(possessing)Tj
4.3937 0 Td
(bat)Tj
1.457 0 Td
(limb)Tj
2.0636 0 Td
(enhanc-)Tj
-34.1232 -1.2982 Td
(ers)Tj
1.3719 0 Td
(exhibit)Tj
2.9764 0 Td
(prolonged)Tj
4.3369 0 Td
(expression)Tj
4.4618 0 Td
(of)Tj
1.0148 0 Td
(limb)Tj
2.0636 0 Td
(elongation)Tj
4.4617 0 Td
(genes)Tj
2.4434 0 Td
([)Tj
0.83 0.64 0.02 0 k
(18)Tj
0 g
(])Tj
1.8539 0 Td
(and)Tj
1.7291 0 Td
(develop)Tj
3.3165 0 Td
(significantly)Tj
-30.03 -1.2983 Td
(longer)Tj
2.7779 0 Td
(limbs)Tj
2.4208 0 Td
(than)Tj
2.0296 0 Td
(control)Tj
3.1237 0 Td
(mice)Tj
2.1543 0 Td
([)Tj
0.83 0.64 0.02 0 k
(19)Tj
0 g
(].)Tj
-11.3101 -1.3039 Td
(The)Tj
1.7858 0 Td
(big)Tj
1.457 0 Td
(brown)Tj
2.8403 0 Td
(bat)Tj
1.457 0 Td
(\()Tj
/F14 1 Tf
[()14()12( )11()8()10(\n)4()1()-4()]TJ
4.0988 0 Td
[()-8()-4()-3()1()-4()]TJ
/F9 1 Tf
(\))Tj
2.914 0 Td
(is)Tj
0.8504 0 Td
(an)Tj
1.2019 0 Td
(insectivore)Tj
4.5638 0 Td
(that)Tj
1.7801 0 Td
(hunts)Tj
2.4831 0 Td
(in)Tj
1.0375 0 Td
(edge)Tj
2.058 0 Td
(spaces)Tj
2.7382 0 Td
(between)Tj
-32.4621 -1.2983 Td
(open)Tj
2.2166 0 Td
(and)Tj
1.7292 0 Td
(cluttered)Tj
3.7587 0 Td
(environments)Tj
5.7939 0 Td
([)Tj
0.83 0.64 0.02 0 k
(20)Tj
0 g
(].)Tj
2.075 0 Td
(This)Tj
1.9899 0 Td
(behavior)Tj
3.7077 0 Td
(requires)Tj
3.4753 0 Td
(the)Tj
1.4683 0 Td
(disambiguation)Tj
6.4516 0 Td
(of)Tj
1.0148 0 Td
(cascades)Tj
-33.681 -1.2982 Td
(of)Tj
1.0147 0 Td
(echoes)Tj
2.8857 0 Td
(from)Tj
2.2053 0 Td
(multiple)Tj
3.566 0 Td
(objects)Tj
2.999 0 Td
(into)Tj
1.8369 0 Td
(separate)Tj
3.4866 0 Td
(percepts)Tj
3.5546 0 Td
([)Tj
0.83 0.64 0.02 0 k
(21)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(22)Tj
0 g
(],)Tj
3.5433 0 Td
(which)Tj
2.6532 0 Td
(must)Tj
2.2223 0 Td
(occur)Tj
2.4775 0 Td
(quickly)Tj
-32.4451 -1.2983 Td
(enough)Tj
3.2201 0 Td
(to)Tj
1.0261 0 Td
(inform)Tj
3.0217 0 Td
(motor)Tj
2.7213 0 Td
(decisions)Tj
3.9061 0 Td
(in)Tj
1.0375 0 Td
(flight.)Tj
2.5341 0 Td
(Because)Tj
3.3959 0 Td
(echolocation)Tj
5.3291 0 Td
(and)Tj
1.7348 0 Td
(flight)Tj
2.3131 0 Td
(are)Tj
1.4456 0 Td
(critical)Tj
2.9537 0 Td
(for)Tj
1.3833 0 Td
(a)Tj
-36.0224 -1.3039 Td
(young)Tj
2.7212 0 Td
(bat's)Tj
2.0353 0 Td
(survival,)Tj
3.5602 0 Td
(the)Tj
1.4741 0 Td
(development)Tj
5.4084 0 Td
(of)Tj
1.0148 0 Td
(hearing)Tj
3.2598 0 Td
(occurs)Tj
2.829 0 Td
(concurrently)Tj
5.3688 0 Td
(with)Tj
1.9956 0 Td
(echolocation)Tj
5.3347 0 Td
(calls)Tj
-35.0019 -1.2983 Td
(and)Tj
1.7291 0 Td
(the)Tj
1.4683 0 Td
(motor)Tj
2.7269 0 Td
(skills)Tj
2.194 0 Td
(involved)Tj
3.651 0 Td
(in)Tj
1.0375 0 Td
(flight)Tj
2.3131 0 Td
([)Tj
0.83 0.64 0.02 0 k
(23)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(28)Tj
0 g
(].)Tj
3.5432 0 Td
(The)Tj
1.7802 0 Td
(echolocation)Tj
5.3348 0 Td
(calls)Tj
1.9332 0 Td
(of)Tj
1.0148 0 Td
(juvenile)Tj
3.3675 0 Td
(big)Tj
1.457 0 Td
(brown)Tj
-33.5506 -1.2983 Td
(bats)Tj
1.8198 0 Td
(undergo)Tj
3.5886 0 Td
(significant)Tj
4.388 0 Td
(changes)Tj
3.4072 0 Td
(between)Tj
3.5263 0 Td
(birth)Tj
2.194 0 Td
(and)Tj
1.7291 0 Td
(three)Tj
2.2621 0 Td
(weeks)Tj
2.6078 0 Td
(of)Tj
1.0148 0 Td
(age,)Tj
1.7688 0 Td
(becoming)Tj
4.184 0 Td
(shorter)Tj
3.0784 0 Td
(in)Tj
-35.5689 -1.3039 Td
(duration)Tj
3.702 0 Td
(and)Tj
1.7291 0 Td
(higher)Tj
2.8006 0 Td
(in)Tj
1.0375 0 Td
(frequency)Tj
4.1896 0 Td
([)Tj
0.83 0.64 0.02 0 k
(26)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(29)Tj
0 g
(].)Tj
3.5432 0 Td
(These)Tj
2.5682 0 Td
(changes)Tj
3.4016 0 Td
(in)Tj
1.0374 0 Td
(echolocation)Tj
5.3348 0 Td
(call)Tj
1.5647 0 Td
(frequencies)Tj
-30.9087 -1.2982 Td
(likely)Tj
2.3527 0 Td
(coincide)Tj
3.6056 0 Td
(with)Tj
2.0013 0 Td
(changes)Tj
3.4015 0 Td
(in)Tj
1.0375 0 Td
(their)Tj
2.109 0 Td
(hearing,)Tj
3.4809 0 Td
(because)Tj
3.3222 0 Td
(the)Tj
1.4683 0 Td
(frequency)Tj
4.1839 0 Td
(place)Tj
2.2677 0 Td
(map)Tj
1.9899 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(cochlea)Tj
-33.7037 -1.2983 Td
(changes)Tj
3.4015 0 Td
(as)Tj
1.0148 0 Td
(it)Tj
0.788 0 Td
(matures,)Tj
3.6794 0 Td
(with)Tj
1.9956 0 Td
(higher)Tj
2.8062 0 Td
(frequency)Tj
4.1839 0 Td
(hearing)Tj
3.2599 0 Td
(developing)Tj
4.5977 0 Td
(later)Tj
1.9956 0 Td
([)Tj
0.83 0.64 0.02 0 k
(30)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7348 0 Td
(31)Tj
0 g
(].)Tj
1.7405 0 Td
(Additionally,)Tj
-31.1979 -1.3039 Td
(the)Tj
1.4683 0 Td
(call)Tj
1.5704 0 Td
(frequencies)Tj
4.7848 0 Td
(of)Tj
1.0148 0 Td
(five)Tj
1.6498 0 Td
(species)Tj
2.999 0 Td
(of)Tj
1.0148 0 Td
(bats)Tj
1.8198 0 Td
(were)Tj
2.126 0 Td
(lower)Tj
2.4491 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4683 0 Td
(first)Tj
1.8029 0 Td
(year)Tj
1.9048 0 Td
(of)Tj
1.0148 0 Td
(life)Tj
1.4457 0 Td
(than)Tj
2.0296 0 Td
(later)Tj
1.9956 0 Td
(in)Tj
1.0318 0 Td
(adult-)Tj
-34.6278 -1.2983 Td
(hood,)Tj
2.5114 0 Td
(suggesting)Tj
4.405 0 Td
(that)Tj
1.7802 0 Td
(fine-tuning)Tj
4.7508 0 Td
(of)Tj
1.0148 0 Td
(echolocation)Tj
5.3348 0 Td
(calls)Tj
1.9275 0 Td
(may)Tj
1.9276 0 Td
(occur)Tj
2.4774 0 Td
(well)Tj
1.8199 0 Td
(after)Tj
2.0352 0 Td
(the)Tj
1.4684 0 Td
(development)Tj
-31.453 -1.2983 Td
(of)Tj
1.0147 0 Td
(hearing)Tj
3.2542 0 Td
(is)Tj
0.8504 0 Td
(complete)Tj
3.8778 0 Td
(\(summarized)Tj
5.5275 0 Td
(in)Tj
1.0318 0 Td
([)Tj
0.83 0.64 0.02 0 k
(32)Tj
0 g
(]\).)Tj
-14.3602 -1.2982 Td
(Because)Tj
3.3958 0 Td
(of)Tj
1.0148 0 Td
(their)Tj
2.109 0 Td
(dependence)Tj
5.006 0 Td
(on)Tj
1.2755 0 Td
(hearing)Tj
3.2599 0 Td
(for)Tj
1.3833 0 Td
(survival)Tj
3.3392 0 Td
(and)Tj
1.7291 0 Td
(their)Tj
2.1089 0 Td
(relatively)Tj
3.8381 0 Td
(well-developed)Tj
-29.6558 -1.3039 Td
(auditory)Tj
3.6056 0 Td
(systems,)Tj
3.5263 0 Td
(echolocating)Tj
5.2894 0 Td
(bats)Tj
1.8198 0 Td
(provide)Tj
3.2882 0 Td
(a)Tj
0.6576 0 Td
(valuable)Tj
3.4923 0 Td
(opportunity)Tj
5.0343 0 Td
(to)Tj
1.0261 0 Td
(examine)Tj
3.6 0 Td
(postnatal)Tj
-31.3396 -1.2983 Td
(hearing)Tj
3.2541 0 Td
(development)Tj
5.4141 0 Td
(in)Tj
1.0318 0 Td
(an)Tj
1.2019 0 Td
(auditory)Tj
3.6113 0 Td
(specialist.)Tj
4.0422 0 Td
(Laryngeally)Tj
4.8359 0 Td
(echolocating)Tj
5.2951 0 Td
(bats)Tj
1.8198 0 Td
(possess)Tj
3.1124 0 Td
(larger)Tj
-33.6186 -1.2983 Td
(cochlea)Tj
3.2031 0 Td
([)Tj
0.83 0.64 0.02 0 k
(33)Tj
0 g
(])Tj
1.8538 0 Td
(relative)Tj
3.1351 0 Td
(to)Tj
1.0262 0 Td
(basicranial)Tj
4.5127 0 Td
(width)Tj
2.5285 0 Td
(than)Tj
2.0296 0 Td
(non-echolocating)Tj
7.2453 0 Td
(or)Tj
1.0941 0 Td
(non-laryngeally)Tj
6.5027 0 Td
(echolocat-)Tj
-33.1311 -1.3039 Td
(ing)Tj
1.5023 0 Td
(bats)Tj
1.8198 0 Td
([)Tj
0.83 0.64 0.02 0 k
(34)Tj
0 g
(].)Tj
2.075 0 Td
(Bats)Tj
1.8935 0 Td
(using)Tj
2.3868 0 Td
(constant-frequency)Tj
7.9596 0 Td
(calls)Tj
1.9332 0 Td
(also)Tj
1.7632 0 Td
(exhibit)Tj
2.9763 0 Td
(overrepresentation)Tj
7.7726 0 Td
(of)Tj
1.0148 0 Td
(dominant)Tj
-33.0971 -1.2982 Td
(call)Tj
1.5703 0 Td
(frequencies)Tj
4.7849 0 Td
(in)Tj
1.0318 0 Td
(basilar)Tj
2.8403 0 Td
(membrane)Tj
4.5694 0 Td
(\(BM\))Tj
2.3698 0 Td
(dimensions)Tj
4.8528 0 Td
(and)Tj
1.7292 0 Td
(spiral)Tj
2.4207 0 Td
(ganglion)Tj
3.7021 0 Td
(density)Tj
3.101 0 Td
([)Tj
0.83 0.64 0.02 0 k
(35)Tj
0 g
(],)Tj
2.075 0 Td
(and)Tj
-35.0473 -1.2983 Td
(extremely)Tj
4.1442 0 Td
(short)Tj
2.2847 0 Td
(hair)Tj
1.8198 0 Td
(cells)Tj
1.9219 0 Td
(and)Tj
1.7291 0 Td
(stereocilia)Tj
4.2463 0 Td
([)Tj
0.83 0.64 0.02 0 k
(36)Tj
0 g
(].)Tj
2.0749 0 Td
(A)Tj
0.9014 0 Td
(recent)Tj
2.71 0 Td
(study)Tj
2.3924 0 Td
(showed)Tj
3.2485 0 Td
(that)Tj
1.7801 0 Td
(echolocating)Tj
5.2894 0 Td
(bats)Tj
-34.5427 -1.3039 Td
(sustain)Tj
3.016 0 Td
(a)Tj
0.652 0 Td
(high)Tj
2.0125 0 Td
(prenatal)Tj
3.4923 0 Td
(cochlear)Tj
3.5773 0 Td
(growth)Tj
3.0727 0 Td
(rate)Tj
1.7462 0 Td
(throughout)Tj
4.7792 0 Td
(development)Tj
5.4084 0 Td
(compared)Tj
4.2463 0 Td
(to)Tj
1.0205 0 Td
(non-echo-)Tj
-33.0234 -1.2983 Td
(locating)Tj
3.4072 0 Td
(bats)Tj
1.8198 0 Td
(and)Tj
1.7291 0 Td
(other)Tj
2.3528 0 Td
(mammals)Tj
4.1499 0 Td
([)Tj
0.83 0.64 0.02 0 k
(37)Tj
0 g
(],)Tj
2.0806 0 Td
(but)Tj
1.5534 0 Td
(which)Tj
2.6475 0 Td
(genes)Tj
2.4434 0 Td
(change)Tj
3.0388 0 Td
(expression)Tj
4.4673 0 Td
(during)Tj
2.931 0 Td
(bat)Tj
1.457 0 Td
(cochlear)Tj
-34.0778 -1.2983 Td
(development)Tj
5.4084 0 Td
(is)Tj
0.8504 0 Td
(unknown.)Tj
4.303 0 Td
(Here,)Tj
2.4321 0 Td
(we)Tj
1.3266 0 Td
(report)Tj
2.7099 0 Td
(on)Tj
1.2756 0 Td
(the)Tj
1.4683 0 Td
(expression)Tj
4.4674 0 Td
(of)Tj
1.0148 0 Td
(selected)Tj
3.3448 0 Td
(hearing-related)Tj
6.3326 0 Td
(genes)Tj
-34.9339 -1.3039 Td
(in)Tj
1.0318 0 Td
(the)Tj
1.474 0 Td
(inner)Tj
2.3754 0 Td
(ears)Tj
1.8141 0 Td
(of)Tj
1.0148 0 Td
(young)Tj
2.7213 0 Td
(big)Tj
1.457 0 Td
(brown)Tj
2.8403 0 Td
(bats)Tj
1.8198 0 Td
(over)Tj
1.9786 0 Td
(a)Tj
0.6519 0 Td
(two-week)Tj
4.0876 0 Td
(period)Tj
2.8346 0 Td
(during)Tj
2.9253 0 Td
(which)Tj
2.6533 0 Td
(their)Tj
2.1032 0 Td
(calls)Tj
1.9333 0 Td
(rap-)Tj
-35.7163 -1.2982 Td
(idly)Tj
1.7121 0 Td
(increase)Tj
3.4752 0 Td
(in)Tj
1.0375 0 Td
(frequency,)Tj
4.4107 0 Td
(becoming)Tj
4.1839 0 Td
(more)Tj
2.3414 0 Td
(similar)Tj
2.982 0 Td
(to)Tj
1.0262 0 Td
(adult)Tj
2.2563 0 Td
(echolocation)Tj
5.3348 0 Td
(calls)Tj
1.9275 0 Td
([)Tj
0.83 0.64 0.02 0 k
(26)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(29)Tj
0 g
(].)Tj
3.5433 0 Td
(Because)Tj
-34.2309 -1.2983 Td
(these)Tj
2.2506 0 Td
(pronounced)Tj
5.1251 0 Td
(frequency)Tj
4.1895 0 Td
(shifts)Tj
2.3188 0 Td
(in)Tj
1.0374 0 Td
(vocalizations)Tj
5.3802 0 Td
(have)Tj
2.0636 0 Td
(been)Tj
2.1203 0 Td
(reported)Tj
3.6623 0 Td
(to)Tj
1.0205 0 Td
(coincide)Tj
3.6113 0 Td
(with)Tj
1.9956 0 Td
(fre-)Tj
-34.7752 -1.2983 Td
(quency)Tj
3.101 0 Td
(shifts)Tj
2.3244 0 Td
(in)Tj
1.0375 0 Td
(hearing)Tj
3.2542 0 Td
(in)Tj
1.0374 0 Td
(several)Tj
2.9367 0 Td
(bat)Tj
1.457 0 Td
(species)Tj
2.999 0 Td
(\(e.g.,)Tj
2.126 0 Td
([)Tj
0.83 0.64 0.02 0 k
(24)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7348 0 Td
(38)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.3946 0 Td
(39)Tj
0 g
(]\),)Tj
2.0807 0 Td
(examining)Tj
4.456 0 Td
(gene)Tj
2.0806 0 Td
(expression)Tj
-32.0199 -1.3039 Td
(during)Tj
2.9253 0 Td
(this)Tj
1.6781 0 Td
(period)Tj
2.8289 0 Td
(may)Tj
1.9333 0 Td
(provide)Tj
3.2881 0 Td
(insight)Tj
2.9537 0 Td
(into)Tj
1.8425 0 Td
(the)Tj
1.4684 0 Td
(regulatory)Tj
4.3199 0 Td
(changes)Tj
3.4016 0 Td
(associated)Tj
4.2576 0 Td
(with)Tj
1.9956 0 Td
(the)Tj
1.4683 0 Td
(devel-)Tj
-34.3613 -1.2983 Td
(opment)Tj
3.3335 0 Td
(of)Tj
1.0148 0 Td
(high)Tj
2.0069 0 Td
(frequency)Tj
4.1896 0 Td
(hearing.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 131.0173 cm
BT
/F3 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Materials)Tj
4.5071 0 Td
(and)Tj
1.989 0 Td
(methods)Tj
/F0 1 Tf
-6.4961 -1.5023 Td
(Subjects)Tj
4.011 0 Td
(and)Tj
1.8662 0 Td
(sample)Tj
3.4063 0 Td
(preparation)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 95.9811 cm
BT
/F9 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Pregnant)Tj
3.8664 0 Td
(female)Tj
/F14 1 Tf
2.8573 0 Td
[()14()12( )11()8()10(\n)4()1()-4()]TJ
3.7587 0 Td
[()-8()-4()-3()1()-4()]TJ
/F9 1 Tf
2.5738 0 Td
(were)Tj
2.1203 0 Td
(captured)Tj
3.7474 0 Td
(in)Tj
1.0318 0 Td
(the)Tj
1.4684 0 Td
(wild)Tj
1.9502 0 Td
(under)Tj
2.6192 0 Td
(a)Tj
0.652 0 Td
(permit)Tj
2.9139 0 Td
(from)Tj
2.2111 0 Td
(the)Tj
1.4683 0 Td
(Maryland)Tj
-33.2388 -1.2982 Td
(Department)Tj
5.0909 0 Td
(of)Tj
1.0148 0 Td
(Natural)Tj
3.2655 0 Td
(Resources.)Tj
4.4674 0 Td
(All)Tj
1.3946 0 Td
(twelve)Tj
2.7496 0 Td
(juvenile)Tj
3.3676 0 Td
(subjects)Tj
3.3788 0 Td
(were)Tj
2.126 0 Td
(born)Tj
2.1543 0 Td
(in)Tj
1.0318 0 Td
(captivity.)Tj
3.8608 0 Td
(Because)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
/I0 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 350.1921 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Age-depen)Tj
4.8047 0 Td
(dent)Tj
2.1331 0 Td
(gene)Tj
2.3953 0 Td
(expression)Tj
4.9678 0 Td
(in)Tj
0.9779 0 Td
(the)Tj
1.5874 0 Td
(inner)Tj
2.3953 0 Td
(ear)Tj
1.6441 0 Td
(of)Tj
1.0347 0 Td
(big)Tj
1.5236 0 Td
(brown)Tj
2.8985 0 Td
(bats)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
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(ONE)Tj
2.3669 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8198 0 Td
(1/journal.po)Tj
5.1236 0 Td
(ne.01866)Tj
4.089 0 Td
(67)Tj
0 g
2.0906 0 Td
(October)Tj
3.7276 0 Td
(26,)Tj
1.5874 0 Td
(2017)Tj
33.5908 0 Td
(2)Tj
0.7654 0 Td
(/)Tj
0.496 0 Td
(15)Tj
/F11 1 Tf
-0.025 Tc
-66.402 84.0904 Td
(decision)Tj
3.2882 0 Td
(to)Tj
0.9496 0 Td
(publish,)Tj
3.1465 0 Td
(or)Tj
0.9992 0 Td
(preparation)Tj
4.4433 0 Td
(of)Tj
0.9496 0 Td
(the)Tj
-13.7764 -1.3748 Td
(manuscript.)Tj
/F10 1 Tf
0 -2.126 Td
(Competing)Tj
4.3795 0 Td
(interests)Tj
3.3307 0 Td
(:)Tj
/F11 1 Tf
0.4819 0 Td
(The)Tj
1.5875 0 Td
(authors)Tj
3.0401 0 Td
(have)Tj
1.963 0 Td
(declared)Tj
-14.7827 -1.3749 Td
(that)Tj
1.6228 0 Td
(no)Tj
1.1693 0 Td
(competing)Tj
4.1599 0 Td
(interests)Tj
ET
endstream
endobj
43 0 obj
<>stream
endstream
endobj
44 0 obj
<>stream
endstream
endobj
45 0 obj
<>stream
endstream
endobj
46 0 obj
<>stream
endstream
endobj
47 0 obj
<>stream
endstream
endobj
48 0 obj
<>stream
endstream
endobj
49 0 obj
<>stream
endstream
endobj
50 0 obj
<>stream
endstream
endobj
51 0 obj
<>stream
endstream
endobj
52 0 obj
<>stream
endstream
endobj
53 0 obj
<>stream
endstream
endobj
54 0 obj
<>stream
endstream
endobj
55 0 obj
<>stream
endstream
endobj
56 0 obj
<>stream
endstream
endobj
57 0 obj
<>stream
endstream
endobj
58 0 obj
<>stream
endstream
endobj
59 0 obj
<>stream
endstream
endobj
60 0 obj
<>stream
endstream
endobj
61 0 obj
<>stream
endstream
endobj
62 0 obj
<>stream
endstream
endobj
63 0 obj
<>stream
endstream
endobj
64 0 obj
<>stream
endstream
endobj
65 0 obj
<>stream
endstream
endobj
66 0 obj
<>stream
endstream
endobj
67 0 obj
<>stream
BT
10.3394 79.2147 Td
(exist.)Tj
ET
Q
endstream
endobj
68 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 12 0 R/Annots 69 0 R/Contents 70 0 R/TrimBox[0 0 612 792]>>
endobj
69 0 obj
[71 0 R 72 0 R 73 0 R 74 0 R 75 0 R 76 0 R 77 0 R 78 0 R 79 0 R 80 0 R 81 0 R 82 0 R 83 0 R 84 0 R]
endobj
71 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186667.ref040)>>
endobj
72 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186667.ref028)>>
endobj
73 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186667.ref041)>>
endobj
74 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186667.ref042)>>
endobj
75 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186667.ref043)>>
endobj
76 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186667.ref044)>>
endobj
77 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186667.ref045)>>
endobj
78 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186667.ref046)>>
endobj
79 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186667.ref016)>>
endobj
80 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186667.ref016)>>
endobj
81 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186667.ref047)>>
endobj
82 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186667.t001)>>
endobj
83 0 obj
<>/Border[0 0 0]/Dest(Rpone.0186667.t002)>>
endobj
84 0 obj
<>/Border[0 0 0]/A 85 0 R>>
endobj
85 0 obj
<>
endobj
70 0 obj
[86 0 R 87 0 R 88 0 R 89 0 R 90 0 R 91 0 R 92 0 R 93 0 R 94 0 R 95 0 R 96 0 R 97 0 R 98 0 R 99 0 R]
endobj
86 0 obj
<>stream
q
0.83 0.64 0.02 0 k
504.6803 693.2976 m
514.0346 693.2976 l
h
f*
492.4913 667.3323 m
501.8457 667.3323 l
h
f*
389.8205 511.3134 m
399.2882 511.3134 l
h
f*
433.8142 459.326 m
443.2819 459.326 l
h
f*
447.7606 459.326 m
457.285 459.326 l
h
f*
410.4 393.9024 m
419.9244 393.9024 l
h
f*
313.7953 380.9197 m
323.3197 380.9197 l
h
f*
516.4724 380.9197 m
525.9402 380.9197 l
h
f*
516.6992 367.937 m
526.1669 367.937 l
h
f*
536.4283 354.8976 m
545.9528 354.8976 l
h
f*
437.6693 341.915 m
447.1937 341.915 l
h
f*
455.074 341.915 m
484.2142 341.915 l
h
f*
344.0126 159.9307 m
373.2094 159.9307 l
h
f*
0 g
1 j
1 J
0 w
10 0 0 10 200.0125 707.4141 cm
BT
/F9 1 Tf
1 TL
-0.01 Tc
0 0 Td
(they)Tj
1.8935 0 Td
(were)Tj
2.0919 0 Td
(group-housed)Tj
5.7543 0 Td
(and)Tj
1.7008 0 Td
(cluster)Tj
2.8233 0 Td
(together,)Tj
3.702 0 Td
(exact)Tj
2.228 0 Td
(dates)Tj
2.2281 0 Td
(of)Tj
0.9921 0 Td
(birth)Tj
2.1543 0 Td
(could)Tj
2.4151 0 Td
(not)Tj
1.5477 0 Td
(be)Tj
1.1339 0 Td
(directly)Tj
3.1747 0 Td
(recorded.)Tj
-33.8397 -1.3039 Td
(Instead,)Tj
3.3278 0 Td
(forearm)Tj
3.3959 0 Td
(length)Tj
2.6929 0 Td
(was)Tj
1.6781 0 Td
(measured)Tj
4.0648 0 Td
(with)Tj
1.9729 0 Td
(calipers)Tj
3.2145 0 Td
(and)Tj
1.7121 0 Td
(used)Tj
2.0353 0 Td
(to)Tj
1.0148 0 Td
(estimate)Tj
3.4979 0 Td
(age)Tj
1.525 0 Td
([)Tj
0.83 0.64 0.02 0 k
(40)Tj
0 g
(].)Tj
2.0466 0 Td
(Forearm)Tj
-32.1786 -1.2982 Td
(length)Tj
2.6928 0 Td
(is)Tj
0.8334 0 Td
(a)Tj
0.652 0 Td
(more)Tj
2.313 0 Td
(accurate)Tj
3.5093 0 Td
(age)Tj
1.525 0 Td
(estimator)Tj
3.9458 0 Td
(than)Tj
2.007 0 Td
(mass)Tj
2.1713 0 Td
(for)Tj
1.3663 0 Td
(big)Tj
1.44 0 Td
(brown)Tj
2.8119 0 Td
(bats,)Tj
2.0126 0 Td
(and)Tj
1.7121 0 Td
(results)Tj
2.7666 0 Td
(from)Tj
2.1827 0 Td
(formulae)Tj
-33.9418 -1.2983 Td
(relating)Tj
3.2258 0 Td
(forearm)Tj
3.3902 0 Td
(length)Tj
2.6929 0 Td
(to)Tj
1.0148 0 Td
(age)Tj
1.525 0 Td
(do)Tj
1.2416 0 Td
(not)Tj
1.559 0 Td
(differ)Tj
2.3471 0 Td
(between)Tj
3.4866 0 Td
(wild)Tj
1.9218 0 Td
(and)Tj
1.7122 0 Td
(captive)Tj
2.999 0 Td
(bats)Tj
1.7972 0 Td
([)Tj
0.83 0.64 0.02 0 k
(28)Tj
0 g
(].)Tj
2.0466 0 Td
(Estimated)Tj
4.1612 0 Td
(ages)Tj
-35.121 -1.2983 Td
(ranged)Tj
2.9536 0 Td
(from)Tj
2.1827 0 Td
(postnatal)Tj
3.8097 0 Td
(day)Tj
1.6158 0 Td
(\(PND\))Tj
2.9026 0 Td
(9)Tj
0.6917 0 Td
(to)Tj
1.0148 0 Td
(19.)Tj
1.3776 0 Td
(Juveniles)Tj
3.7474 0 Td
(were)Tj
2.0976 0 Td
(weighed,)Tj
3.719 0 Td
(anesthetized)Tj
5.091 0 Td
(with)Tj
1.9729 0 Td
(isoflurane)Tj
-33.1764 -1.3039 Td
(and)Tj
1.7121 0 Td
(euthanized)Tj
4.5524 0 Td
(via)Tj
1.3549 0 Td
(decapitation.)Tj
5.3121 0 Td
(All)Tj
1.3833 0 Td
(procedures)Tj
4.6148 0 Td
(were)Tj
2.0976 0 Td
(in)Tj
1.0205 0 Td
(accordance)Tj
4.6771 0 Td
(with)Tj
1.9729 0 Td
(the)Tj
1.4514 0 Td
(National)Tj
3.6453 0 Td
(Institutes)Tj
-33.7944 -1.2982 Td
(of)Tj
1.0034 0 Td
(Health's)Tj
/F14 1 Tf
3.4412 0 Td
[()13()12(\n)4()4()]TJ
2.5512 0 Td
[()9()11()]TJ
1.2926 0 Td
[( )10()6()]TJ
1.4003 0 Td
[()-2()16()20()]TJ
2.0579 0 Td
[()16()6()]TJ
1.7122 0 Td
[()39()-3()]TJ
1.6157 0 Td
[()11()]TJ
0.9411 0 Td
[()-3()22()4()11()20()22( )11()11()-20()]TJ
4.5241 0 Td
[()30()18(\n)12()6()11( )-4()]TJ
/F9 1 Tf
(,)Tj
3.6736 0 Td
(and)Tj
1.7122 0 Td
(were)Tj
2.0976 0 Td
(approved)Tj
3.9231 0 Td
(by)Tj
1.1735 0 Td
(the)Tj
1.4514 0 Td
(Johns)Tj
-34.5711 -1.2983 Td
(Hopkins)Tj
3.6396 0 Td
(University)Tj
4.3427 0 Td
(Institutional)Tj
5.0853 0 Td
(Animal)Tj
3.1861 0 Td
(Care)Tj
2.0863 0 Td
(and)Tj
1.7121 0 Td
(Use)Tj
1.7235 0 Td
(Committee)Tj
4.6884 0 Td
(\(protocol)Tj
3.8835 0 Td
(BA14A111\).)Tj
5.0513 0 Td
(Sam-)Tj
-35.3988 -1.3039 Td
(ples)Tj
1.7404 0 Td
(were)Tj
2.1033 0 Td
(also)Tj
1.7405 0 Td
(obtained)Tj
3.685 0 Td
(from)Tj
2.1826 0 Td
(two)Tj
1.6895 0 Td
(adult)Tj
2.228 0 Td
(individuals)Tj
4.5808 0 Td
(under)Tj
2.5908 0 Td
(a)Tj
0.6463 0 Td
(protocol)Tj
3.549 0 Td
(approved)Tj
3.9288 0 Td
(by)Tj
1.1678 0 Td
(the)Tj
1.4513 0 Td
(University)Tj
-33.2841 -1.2983 Td
(of)Tj
1.0034 0 Td
(Maryland)Tj
4.0819 0 Td
(Institutional)Tj
5.0796 0 Td
(Animal)Tj
3.1861 0 Td
(Care)Tj
2.0863 0 Td
(and)Tj
1.7121 0 Td
(Use)Tj
1.7235 0 Td
(Committee)Tj
4.6885 0 Td
(\(R-13-76\).)Tj
-0.004 Tc
-22.3652 -1.2983 Td
(Inner)Tj
2.4548 0 Td
(ear)Tj
1.4513 0 Td
(samples,)Tj
3.6056 0 Td
(consisting)Tj
4.269 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(entire)Tj
2.5512 0 Td
(otic)Tj
1.7178 0 Td
(capsule)Tj
3.1521 0 Td
(\(both)Tj
2.3981 0 Td
(cochleae)Tj
3.6283 0 Td
(and)Tj
1.7348 0 Td
(vestibular)Tj
-30.6423 -1.3039 Td
(organs\),)Tj
3.4695 0 Td
(were)Tj
2.126 0 Td
(collected)Tj
3.736 0 Td
(immediately)Tj
5.2044 0 Td
(post-mortem)Tj
5.4935 0 Td
(and)Tj
1.7292 0 Td
(placed)Tj
2.7892 0 Td
(into)Tj
1.8425 0 Td
(liquid)Tj
2.5625 0 Td
(nitrogen)Tj
3.651 0 Td
(prior)Tj
2.2564 0 Td
(to)Tj
-34.8602 -1.2982 Td
(storage)Tj
3.0784 0 Td
(at)Tj
0.9524 0 Td
(-80C)Tj
2.5795 0 Td
(until)Tj
2.109 0 Td
(extraction.)Tj
4.4787 0 Td
(Both)Tj
2.1316 0 Td
(left)Tj
1.4797 0 Td
(and)Tj
1.7291 0 Td
(right)Tj
2.1487 0 Td
(cochleae)Tj
3.6283 0 Td
(from)Tj
2.2053 0 Td
(an)Tj
1.2019 0 Td
(individual)Tj
4.2916 0 Td
(were)Tj
2.1203 0 Td
(pooled)Tj
-34.1345 -1.2983 Td
(and)Tj
1.7291 0 Td
(processed)Tj
4.1329 0 Td
(together.)Tj
3.7643 0 Td
(Samples)Tj
3.498 0 Td
(were)Tj
2.1203 0 Td
(homogenized)Tj
5.6522 0 Td
(with)Tj
1.9956 0 Td
(a)Tj
0.652 0 Td
(mortar)Tj
3.0217 0 Td
(and)Tj
1.7291 0 Td
(pestle)Tj
2.4945 0 Td
(while)Tj
2.3641 0 Td
(submerged)Tj
-33.1538 -1.3039 Td
(in)Tj
1.0318 0 Td
(liquid)Tj
2.5681 0 Td
(nitrogen.)Tj
3.8721 0 Td
(RNA)Tj
2.2621 0 Td
(extraction)Tj
4.2576 0 Td
(was)Tj
1.7007 0 Td
(performed)Tj
4.4674 0 Td
(using)Tj
2.3868 0 Td
(a)Tj
0.6576 0 Td
(mirVana)Tj
3.7871 0 Td
(kit)Tj
1.2812 0 Td
(\(Ambion\),)Tj
4.4617 0 Td
(with)Tj
1.9956 0 Td
(added)Tj
-34.7298 -1.2983 Td
(proteinase)Tj
4.3709 0 Td
(K)Tj
0.8958 0 Td
(\(Sigma)Tj
3.016 0 Td
(Aldrich\))Tj
3.6113 0 Td
(to)Tj
1.0262 0 Td
(improve)Tj
3.5773 0 Td
(yield)Tj
2.143 0 Td
([)Tj
0.83 0.64 0.02 0 k
(41)Tj
0 g
(].)Tj
2.0749 0 Td
(All)Tj
1.3946 0 Td
(samples)Tj
3.3846 0 Td
(were)Tj
2.1203 0 Td
(treated)Tj
2.999 0 Td
(with)Tj
1.9956 0 Td
(TURBO)Tj
-32.6095 -1.2982 Td
(DNA-free)Tj
4.2349 0 Td
(DNAse)Tj
3.1578 0 Td
(\(Ambion\))Tj
4.2349 0 Td
(and)Tj
1.7291 0 Td
(cleaned)Tj
3.2485 0 Td
(with)Tj
1.9956 0 Td
(isopropanol)Tj
5.0059 0 Td
(and)Tj
1.7292 0 Td
(ethanol.)Tj
3.4299 0 Td
(Sample)Tj
3.1351 0 Td
(quality)Tj
2.9536 0 Td
(was)Tj
-34.8545 -1.2983 Td
(checked)Tj
3.4639 0 Td
(on)Tj
1.2755 0 Td
(a)Tj
0.652 0 Td
(Nanodrop)Tj
4.371 0 Td
(spectrophotometer)Tj
7.8179 0 Td
(and)Tj
1.7291 0 Td
(reverse)Tj
3.0501 0 Td
(transcribed)Tj
4.7508 0 Td
(with)Tj
1.9956 0 Td
(M-MLV)Tj
3.5886 0 Td
(\(Thermo)Tj
-32.6945 -1.3039 Td
(Fisher\))Tj
3.0387 0 Td
(using)Tj
2.3867 0 Td
(a)Tj
0.6577 0 Td
(50/50)Tj
2.4491 0 Td
(mix)Tj
1.7745 0 Td
(of)Tj
1.0148 0 Td
(oligo-dT)Tj
3.702 0 Td
(and)Tj
1.7291 0 Td
(random)Tj
3.4299 0 Td
(primers)Tj
3.3505 0 Td
(to)Tj
1.0205 0 Td
(lower)Tj
2.4548 0 Td
(the)Tj
1.4683 0 Td
(risk)Tj
1.7178 0 Td
(of)Tj
1.0148 0 Td
(bias)Tj
1.7858 0 Td
(or)Tj
1.0999 0 Td
(trun-)Tj
-34.0949 -1.2983 Td
(cated)Tj
2.3243 0 Td
(transcripts)Tj
4.4731 0 Td
(associated)Tj
4.2576 0 Td
(with)Tj
1.9956 0 Td
(a)Tj
0.6576 0 Td
(single)Tj
2.5285 0 Td
(priming)Tj
3.4753 0 Td
(method)Tj
3.3278 0 Td
([)Tj
0.83 0.64 0.02 0 k
(42)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7348 0 Td
(43)Tj
0 g
(].)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 425.0267 cm
BT
/F0 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Gene)Tj
2.6409 0 Td
(selection)Tj
4.115 0 Td
(and)Tj
1.8614 0 Td
(primer)Tj
3.0237 0 Td
(design)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 408.0188 cm
BT
/F9 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Candidate)Tj
4.3426 0 Td
(genes)Tj
2.4434 0 Td
(were)Tj
2.1204 0 Td
(selected)Tj
3.3505 0 Td
(based)Tj
2.4718 0 Td
(on)Tj
1.2756 0 Td
(one)Tj
1.6951 0 Td
(or)Tj
1.0998 0 Td
(more)Tj
2.3414 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(following)Tj
3.9799 0 Td
(criteria:)Tj
3.3051 0 Td
(upregulated)Tj
4.9833 0 Td
(in)Tj
-35.892 -1.3039 Td
(an)Tj
1.2018 0 Td
(echolocating)Tj
5.2894 0 Td
(bat)Tj
1.4627 0 Td
(vs.)Tj
1.2586 0 Td
(a)Tj
0.652 0 Td
(non-echolocating)Tj
7.2509 0 Td
(bat)Tj
1.457 0 Td
(\(e.g.,)Tj
2.126 0 Td
([)Tj
0.83 0.64 0.02 0 k
(44)Tj
0 g
(]\);)Tj
2.4151 0 Td
(upregulated)Tj
4.9833 0 Td
(in)Tj
1.0375 0 Td
(an)Tj
1.2018 0 Td
(adult)Tj
2.2507 0 Td
(mouse)Tj
2.863 0 Td
(rela-)Tj
-35.4498 -1.2982 Td
(tive)Tj
1.661 0 Td
(to)Tj
1.0262 0 Td
(juvenile)Tj
3.3675 0 Td
(mouse)Tj
2.8573 0 Td
(\(e.g.,)Tj
2.126 0 Td
([)Tj
0.83 0.64 0.02 0 k
(45)Tj
0 g
(]\);)Tj
2.4208 0 Td
(expressed)Tj
4.0932 0 Td
(in)Tj
1.0318 0 Td
(mid-)Tj
2.1883 0 Td
(to)Tj
1.0261 0 Td
(late-)Tj
1.9729 0 Td
(development)Tj
5.4085 0 Td
(\(e.g.,)Tj
2.126 0 Td
([)Tj
0.83 0.64 0.02 0 k
(46)Tj
0 g
(]\);)Tj
2.4151 0 Td
(evidence)Tj
-33.7207 -1.2983 Td
(of)Tj
1.0147 0 Td
(parallel)Tj
3.1351 0 Td
(or)Tj
1.0999 0 Td
(convergent)Tj
4.6828 0 Td
(evolution)Tj
4.0025 0 Td
(between)Tj
3.5263 0 Td
(echolocating)Tj
5.295 0 Td
(bats)Tj
1.8199 0 Td
(and)Tj
1.7291 0 Td
(whales)Tj
2.897 0 Td
(\(e.g.,)Tj
2.126 0 Td
([)Tj
0.83 0.64 0.02 0 k
(16)Tj
0 g
(]\);)Tj
2.4151 0 Td
(evidence)Tj
-33.7434 -1.3039 Td
(of)Tj
1.0147 0 Td
(parallel)Tj
3.1351 0 Td
(or)Tj
1.0999 0 Td
(convergent)Tj
4.6828 0 Td
(evolution)Tj
4.0025 0 Td
(between)Tj
3.5263 0 Td
(distantly)Tj
3.6566 0 Td
(related)Tj
2.948 0 Td
(echolocating)Tj
5.2895 0 Td
(bats)Tj
1.8198 0 Td
(\(e.g.,)Tj
2.126 0 Td
([)Tj
0.83 0.64 0.02 0 k
(16)Tj
0 g
(]\);)Tj
2.4151 0 Td
(or)Tj
-35.7163 -1.2983 Td
(involved)Tj
3.651 0 Td
(in)Tj
1.0318 0 Td
(formation)Tj
4.2632 0 Td
(of)Tj
1.0148 0 Td
(essential)Tj
3.583 0 Td
(cochlear)Tj
3.5773 0 Td
(structures)Tj
4.1839 0 Td
(\(e.g.,)Tj
2.1203 0 Td
([)Tj
0.83 0.64 0.02 0 k
(47)Tj
0 g
(];)Tj
0.83 0.64 0.02 0 k
2.0806 0 Td
(Table)Tj
2.4378 0 Td
(1)Tj
0 g
(\).)Tj
1.2643 0 Td
(For)Tj
1.627 0 Td
(each)Tj
2.0296 0 Td
(gene,)Tj
2.3017 0 Td
(all)Tj
-35.1663 -1.2982 Td
(available)Tj
3.668 0 Td
(mRNA)Tj
3.0784 0 Td
(transcripts)Tj
4.473 0 Td
(from)Tj
/F14 1 Tf
2.2053 0 Td
[()14()12( )11()8()10(\n)4()1()-4()]TJ
3.7588 0 Td
[()-8()-4()-3()1()-4()]TJ
/F9 1 Tf
2.5738 0 Td
(and)Tj
1.7291 0 Td
(all)Tj
1.1509 0 Td
(bats)Tj
1.8198 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(genus)Tj
/F14 1 Tf
2.5454 0 Td
[(!)47()3()12( )7(\n)-4()]TJ
/F9 1 Tf
2.8857 0 Td
(\(another)Tj
-32.3714 -1.2983 Td
(genus)Tj
2.5454 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4684 0 Td
(same)Tj
2.2563 0 Td
(family,)Tj
2.9537 0 Td
(Vespertilionidae\),)Tj
7.3644 0 Td
(were)Tj
2.1203 0 Td
(downloaded)Tj
5.1533 0 Td
(from)Tj
2.211 0 Td
(GenBank)Tj
3.9628 0 Td
(\(NCBI\))Tj
3.2202 0 Td
(and)Tj
-34.2933 -1.3039 Td
(aligned)Tj
3.1294 0 Td
(using)Tj
2.3924 0 Td
(Clustal)Tj
2.9934 0 Td
(Omega)Tj
3.1124 0 Td
(\(EMBL-EBI\).)Tj
5.5445 0 Td
(Sequences)Tj
4.3313 0 Td
(from)Tj
/F14 1 Tf
2.2054 0 Td
[(!)47()3()12( )7(\n)-4()]TJ
/F9 1 Tf
2.8913 0 Td
(spp.)Tj
1.8368 0 Td
(were)Tj
2.126 0 Td
(included)Tj
3.7077 0 Td
(in)Tj
1.0375 0 Td
(order)Tj
-35.3081 -1.2983 Td
(to)Tj
1.0261 0 Td
(reduce)Tj
2.914 0 Td
(the)Tj
1.4683 0 Td
(risk)Tj
1.7178 0 Td
(of)Tj
1.0148 0 Td
(designing)Tj
4.0932 0 Td
(primers)Tj
3.3505 0 Td
(in)Tj
1.0375 0 Td
(regions)Tj
3.1635 0 Td
(with)Tj
1.9955 0 Td
(polymorphic)Tj
5.3802 0 Td
(sites.)Tj
2.1543 0 Td
(All)Tj
1.4003 0 Td
(primer)Tj
2.9877 0 Td
(pairs)Tj
-33.7037 -1.2983 Td
(were)Tj
2.1203 0 Td
(designed)Tj
3.7643 0 Td
(within)Tj
2.812 0 Td
(the)Tj
1.474 0 Td
(same)Tj
2.2564 0 Td
(exon)Tj
2.1656 0 Td
(to)Tj
1.0205 0 Td
(permit)Tj
2.9196 0 Td
(preliminary)Tj
4.9436 0 Td
(testing)Tj
2.88 0 Td
(on)Tj
1.2756 0 Td
(genomic)Tj
3.6737 0 Td
(DNA.)Tj
-30.1094 -1.3039 Td
(To)Tj
1.3379 0 Td
(identify)Tj
3.2995 0 Td
(exons)Tj
2.5228 0 Td
(in)Tj
1.0375 0 Td
(an)Tj
/F14 1 Tf
1.2019 0 Td
[()14()12( )11()8()10(\n)4()1()-4()]TJ
3.7587 0 Td
[()-8()-4()-3()1()-4()]TJ
/F9 1 Tf
2.5738 0 Td
(transcript,)Tj
4.337 0 Td
(exonic)Tj
2.8517 0 Td
(regions)Tj
3.1634 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
/F14 1 Tf
1.474 0 Td
[(!)47()3()12( )7(\n)-4()]TJ
2.8857 0 Td
[( )12()4()1(\n)12()-8()10(")-8()-4()]TJ
/F9 1 Tf
-32.6549 -1.2982 Td
(transcript,)Tj
4.3369 0 Td
(as)Tj
1.0148 0 Td
(identified)Tj
4.0592 0 Td
(in)Tj
1.0318 0 Td
(Ensembl,)Tj
3.9231 0 Td
(were)Tj
2.1203 0 Td
(blasted)Tj
3.0161 0 Td
(against)Tj
3.033 0 Td
(the)Tj
1.4684 0 Td
(transcript)Tj
4.1102 0 Td
(for)Tj
/F14 1 Tf
1.3833 0 Td
[()14()12( )11()8()10(\n)4()1()-4()]TJ
3.7644 0 Td
[()-8()-4()-3()1()-4()]TJ
/F9 1 Tf
(.)Tj
2.7949 0 Td
(If)Tj
-36.0564 -1.2983 Td
(the)Tj
/F14 1 Tf
1.4683 0 Td
[(!)47()3()12( )7(\n)-4()]TJ
/F9 1 Tf
2.8856 0 Td
(transcript)Tj
4.1102 0 Td
(was)Tj
1.7008 0 Td
(not)Tj
1.5704 0 Td
(available)Tj
3.668 0 Td
(in)Tj
1.0375 0 Td
(Ensembl,)Tj
3.9174 0 Td
(the)Tj
1.4741 0 Td
(mouse)Tj
2.8573 0 Td
(\()Tj
/F14 1 Tf
[(!)29()-4()]TJ
2.2903 0 Td
[()18()-4()-3()1()4( )12()-4()]TJ
/F9 1 Tf
(\))Tj
4.1839 0 Td
(transcript)Tj
4.1159 0 Td
(was)Tj
-35.2797 -1.3039 Td
(used)Tj
2.0579 0 Td
(instead.)Tj
3.3052 0 Td
(If)Tj
0.8504 0 Td
(the)Tj
1.4683 0 Td
(exonic)Tj
2.8573 0 Td
(region)Tj
2.8006 0 Td
(was)Tj
1.7008 0 Td
(conserved)Tj
4.2576 0 Td
(among)Tj
/F14 1 Tf
2.9934 0 Td
[()14()12( )11()8()10(\n)4()1()-4()]TJ
/F9 1 Tf
3.7643 0 Td
(and)Tj
/F14 1 Tf
1.7292 0 Td
[(!)47()3()12( )7(\n)-4()]TJ
/F9 1 Tf
2.8856 0 Td
(spp.,)Tj
2.0636 0 Td
(it)Tj
0.7881 0 Td
(was)Tj
-33.5223 -1.2983 Td
(entered)Tj
3.2371 0 Td
(into)Tj
1.8368 0 Td
(Primer-BLAST)Tj
6.2759 0 Td
(\(NCBI\).)Tj
3.4412 0 Td
(Potential)Tj
3.8041 0 Td
(primer)Tj
2.9877 0 Td
(pairs)Tj
2.1713 0 Td
(were)Tj
2.126 0 Td
(checked)Tj
3.4639 0 Td
(for)Tj
1.389 0 Td
(specificity)Tj
-30.733 -1.2982 Td
(against)Tj
/F14 1 Tf
3.0273 0 Td
[()14()12( )11()8()10(\n)4()1()-4()]TJ
3.7587 0 Td
[()-8()-4()-3()1()-4()]TJ
/F9 1 Tf
2.5739 0 Td
(RefSeq)Tj
2.9593 0 Td
(data,)Tj
2.1374 0 Td
(potential)Tj
3.7643 0 Td
(for)Tj
1.3833 0 Td
(cross-)Tj
2.5966 0 Td
(and)Tj
1.7291 0 Td
(self-dimerization,)Tj
7.2566 0 Td
(and)Tj
1.7348 0 Td
(potential)Tj
3.7587 0 Td
(to)Tj
-36.68 -1.304 Td
(form)Tj
2.2053 0 Td
(hairpins)Tj
3.5149 0 Td
(using)Tj
2.3868 0 Td
(Beacon)Tj
3.1351 0 Td
(Designer)Tj
3.8211 0 Td
(\(Premier)Tj
3.7927 0 Td
(Biosoft\).)Tj
3.5943 0 Td
(Only)Tj
2.2167 0 Td
(primers)Tj
3.3505 0 Td
(that)Tj
1.7802 0 Td
(were)Tj
2.1203 0 Td
(100%)Tj
2.4037 0 Td
(con-)Tj
-34.3216 -1.2982 Td
(served)Tj
2.7779 0 Td
(across)Tj
2.6815 0 Td
(all)Tj
1.1452 0 Td
(known)Tj
3.0047 0 Td
(transcripts)Tj
4.4731 0 Td
(from)Tj
/F14 1 Tf
2.2053 0 Td
[()14()12( )11()8()10(\n)4()1()-4()]TJ
/F9 1 Tf
3.7587 0 Td
(and)Tj
/F14 1 Tf
1.7292 0 Td
[(!)47()3()12( )7(\n)-4()]TJ
/F9 1 Tf
2.8856 0 Td
(spp.)Tj
1.8425 0 Td
(were)Tj
2.1203 0 Td
(used)Tj
2.0636 0 Td
(for)Tj
1.3833 0 Td
(quantitative)Tj
-32.0709 -1.2983 Td
(PCR.)Tj
2.2903 0 Td
(Primer)Tj
3.0274 0 Td
(sequences)Tj
4.2236 0 Td
(are)Tj
1.4457 0 Td
(given)Tj
2.3811 0 Td
(in)Tj
0.83 0.64 0.02 0 k
1.0318 0 Td
(Table)Tj
2.4434 0 Td
(2)Tj
0 g
(.)Tj
-15.6471 -1.2983 Td
(Five-point)Tj
4.3823 0 Td
(dilution)Tj
3.4129 0 Td
(series)Tj
2.4264 0 Td
(\(1:3)Tj
1.7348 0 Td
(or)Tj
1.0999 0 Td
(1:4\))Tj
1.7348 0 Td
(were)Tj
2.1259 0 Td
(performed)Tj
4.4674 0 Td
(for)Tj
1.389 0 Td
(each)Tj
2.0239 0 Td
(gene)Tj
2.0806 0 Td
(and)Tj
1.7348 0 Td
(only)Tj
1.9729 0 Td
(primer)Tj
2.9934 0 Td
(pairs)Tj
-34.7752 -1.3039 Td
(with)Tj
1.9955 0 Td
(efficiencies)Tj
4.6261 0 Td
(greater)Tj
3.0047 0 Td
(than)Tj
2.0296 0 Td
(90%)Tj
1.9276 0 Td
(after)Tj
2.0352 0 Td
(exclusion)Tj
3.9912 0 Td
(of)Tj
1.0148 0 Td
(non-linear)Tj
4.4674 0 Td
(dilutions)Tj
3.77 0 Td
(\(typically)Tj
3.9005 0 Td
(at)Tj
0.9524 0 Td
(the)Tj
1.4684 0 Td
(high-)Tj
-35.1834 -1.2982 Td
(est)Tj
1.3039 0 Td
(or)Tj
1.0941 0 Td
(lowest)Tj
2.744 0 Td
(concentration)Tj
5.8166 0 Td
(of)Tj
1.0148 0 Td
(template\))Tj
4.0195 0 Td
(were)Tj
2.126 0 Td
(selected)Tj
3.3449 0 Td
(for)Tj
1.3889 0 Td
(use.)Tj
1.7575 0 Td
(Post-amplification)Tj
7.6138 0 Td
(melt)Tj
2.0069 0 Td
(curves)Tj
-34.2309 -1.2983 Td
(were)Tj
2.1203 0 Td
(checked)Tj
3.4695 0 Td
(to)Tj
1.0205 0 Td
(ensure)Tj
2.88 0 Td
(each)Tj
2.0239 0 Td
(product)Tj
3.3959 0 Td
(consisted)Tj
3.9345 0 Td
(of)Tj
1.0148 0 Td
(a)Tj
0.6576 0 Td
(single,)Tj
2.7552 0 Td
(narrow)Tj
3.1351 0 Td
(peak,)Tj
2.3188 0 Td
(and)Tj
1.7291 0 Td
(gel)Tj
1.3549 0 Td
(electrophore-)Tj
-31.8101 -1.3039 Td
(sis)Tj
1.2075 0 Td
(was)Tj
1.7008 0 Td
(performed)Tj
4.4674 0 Td
(for)Tj
1.3889 0 Td
(each)Tj
2.0239 0 Td
(amplicon)Tj
3.9855 0 Td
(to)Tj
1.0262 0 Td
(ensure)Tj
2.8743 0 Td
(a)Tj
0.6519 0 Td
(single)Tj
2.5342 0 Td
(product)Tj
3.3902 0 Td
(of)Tj
1.0148 0 Td
(correct)Tj
3.0387 0 Td
(size)Tj
1.6895 0 Td
(was)Tj
1.6951 0 Td
(produced)Tj
-32.6889 -1.2983 Td
(during)Tj
2.9253 0 Td
(amplification.)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
/I0 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 350.1921 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Age-depen)Tj
4.8047 0 Td
(dent)Tj
2.1331 0 Td
(gene)Tj
2.3953 0 Td
(expression)Tj
4.9678 0 Td
(in)Tj
0.9779 0 Td
(the)Tj
1.5874 0 Td
(inner)Tj
2.3953 0 Td
(ear)Tj
1.6441 0 Td
(of)Tj
1.0347 0 Td
(big)Tj
1.5236 0 Td
(brown)Tj
2.8985 0 Td
(bats)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
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(ONE)Tj
2.3669 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8198 0 Td
(1/journal.po)Tj
5.1236 0 Td
(ne.01866)Tj
4.089 0 Td
(67)Tj
0 g
2.0906 0 Td
(October)Tj
3.7276 0 Td
(26,)Tj
1.5874 0 Td
(2017)Tj
33.5908 0 Td
(3)Tj
0.7654 0 Td
(/)Tj
ET
endstream
endobj
87 0 obj
<>stream
endstream
endobj
88 0 obj
<>stream
endstream
endobj
89 0 obj
<>stream
endstream
endobj
90 0 obj
<>stream
endstream
endobj
91 0 obj
<>stream
endstream
endobj
92 0 obj
<>stream
endstream
endobj
93 0 obj
<>stream
endstream
endobj
94 0 obj
<>stream
endstream
endobj
95 0 obj
<>stream
endstream
endobj
96 0 obj
<>stream
endstream
endobj
97 0 obj
<>stream
endstream
endobj
98 0 obj
<>stream
endstream
endobj
99 0 obj
<>stream
BT
66.402 0 Td
(15)Tj
ET
Q
endstream
endobj
100 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 12 0 R/Annots 103 0 R/Contents 104 0 R/TrimBox[0 0 612 792]>>
endobj
102 0 obj
<>
endobj
105 0 obj
<>
endobj
108 0 obj
<>stream
MinionPro-Regular 6 )
H? HD H\ ' - 3 > H N T Z ` j q t { +2=CIU[cnz~
"(.9CIOU[elov|&-8>DPV^iuy &+/49@DGLPU[]_ahjmru|
&-4;BIPW^elsz
")07>ELSZahov} %,3:AHOV]dkry#/;JTey ! ( / 6 = D K R Y ` g n u |
$
+
2
9
@
G
N
U
\
c
j
q
x
'.5<CJQX_fmt{ #*18?FMT[bkry
"
)
0
7
>
E
J
O
W
d
q
v
$+29@GNU\cjqx '.5<CJQX_fmt{ #*18?FMT[bipw~
&-4;BIPW^elsz !(/6=DOVcpuz-B\v$<Tdy*5@Tanz!2>O_fmt{ $-6?HQZclu~ )2;DMV^gpy $-6?HQZclu~ )2;DM\enwcommaaccentAbreveAmacronAogonekAEacuteCacuteCcaronCcircumflexCdotaccentDcaronDcroatEbreveEcaronEdotaccentEmacronEngEogonekGbreveGcircumflexGcommaaccentGdotaccentHbarHcircumflexIbreveIJImacronIogonekItildeJcircumflexKcommaaccentLacuteLcaronLcommaaccentLdotNacuteNcaronNcommaaccentObreveOhungarumlautOmacronOslashacuteRacuteRcaronRcommaaccentSacuteScedillaScircumflexScommaaccentTbarTcaronTcommaaccentUbreveUhungarumlautUmacronUogonekUringUtildeWacuteWcircumflexWdieresisWgraveYcircumflexYgraveZacuteZdotaccentIdotaccentabreveamacronaogonekaeacutecacuteccaronccircumflexcdotaccentdcarondcroatebreveecaronedotaccentemacronengeogonekgbrevegcircumflexgcommaaccentgdotaccenthbarhcircumflexibreveijimacroniogonekitildejcircumflexkcommaaccentlacutelcaronlcommaaccentldotnacutencaronncommaaccentobreveohungarumlautomacronoslashacuteracutercaronrcommaaccentsacutescedillascircumflexscommaaccenttbartcarontcommaaccentubreveuhungarumlautumacronuogonekuringutildewacutewcircumflexwdieresiswgraveycircumflexygravezacutezdotaccentkgreenlandiclongsnapostrophetonosdieresistonosAlphaBetaGammaDeltaEpsilonZetaEtaThetaIotaKappaLambdaMuNuXiOmicronPiRhoSigmaTauUpsilonPhiChiPsiOmegaAlphatonosEpsilontonosEtatonosIotatonosIotadieresisOmicrontonosUpsilontonosUpsilondieresisOmegatonosuni1FBBuni1F09uni1F0Duni1F0Buni1F0Funi1FB8uni1FBAuni1FBCuni1F89uni1F8Duni1F8Buni1F8Funi1F88uni1F8Cuni1F8Auni1F8Euni1F08uni1F0Cuni1F0Auni1F0Euni1FB9uni1FC9uni1F19uni1F1Duni1F1Buni1FC8uni1F18uni1F1Cuni1F1Auni1FCBuni1F29uni1F2Duni1F2Buni1F2Funi1FCAuni1FCCuni1F99uni1F9Duni1F9Buni1F9Funi1F98uni1F9Cuni1F9Auni1F9Euni1F28uni1F2Cuni1F2Auni1F2Euni1FDBuni1F39uni1F3Duni1F3Buni1F3Funi1FD8uni1FDAuni1F38uni1F3Cuni1F3Auni1F3Euni1FD9uni1FFBuni1F69uni1F6Duni1F6Buni1F6Funi1FFAuni1FFCuni1FA9uni1FADuni1FABuni1FAFuni1FA8uni1FACuni1FAAuni1FAEuni1F68uni1F6Cuni1F6Auni1F6Euni1FF9uni1F49uni1F4Duni1F4Buni1FF8uni1F48uni1F4Cuni1F4Auni1FECuni1FEBuni1F59uni1F5Duni1F5Buni1F5Funi1FE8uni1FEAuni1FE9alphabetagammadeltaepsilonzetaetathetaiotakappalambdanuxiomicronpirhosigmatauupsilonphichipsiomegaalphatonosepsilontonosetatonosiotatonosiotadieresisomicrontonosupsilontonosupsilondieresisomegatonosiotadieresistonosupsilondieresistonosuni03C2uni0374uni0375uni037Euni03D0uni03DAuni03DEuni03E0uni03F0uni1FBDuni1FBEuni1FC1uni1FCDuni1FCEuni1FCFuni1FDDuni1FDEuni1FDFuni1FEDuni1FEEuni1FFEuni1F00uni1F01uni1F02uni1F03uni1F04uni1F05uni1F06uni1F07uni1F10uni1F11uni1F12uni1F13uni1F14uni1F15uni1F20uni1F21uni1F22uni1F23uni1F24uni1F25uni1F26uni1F27uni1F30uni1F31uni1F32uni1F33uni1F34uni1F35uni1F36uni1F37uni1F40uni1F41uni1F42uni1F43uni1F44uni1F45uni1F50uni1F51uni1F52uni1F53uni1F54uni1F55uni1F56uni1F57uni1F60uni1F61uni1F62uni1F63uni1F64uni1F65uni1F66uni1F67uni1F70uni1F71uni1F72uni1F73uni1F74uni1F75uni1F76uni1F77uni1F78uni1F79uni1F7Auni1F7Buni1F7Cuni1F7Duni1F80uni1F81uni1F82uni1F83uni1F84uni1F85uni1F86uni1F87uni1F90uni1F91uni1F92uni1F93uni1F94uni1F95uni1F96uni1F97uni1FA0uni1FA1uni1FA2uni1FA3uni1FA4uni1FA5uni1FA6uni1FA7uni1FB0uni1FB1uni1FB2uni1FB3uni1FB6uni1FB7uni1FC2uni1FC3uni1FC4uni1FC6uni1FC7uni1FD0uni1FD1uni1FD2uni1FD3uni1FD6uni1FD7uni1FE0uni1FE1uni1FE2uni1FE3uni1FE4uni1FE5uni1FE6uni1FF2uni1FF3uni1FF4uni1FF6uni1FF7uni1FB4uni1FE7uniEFD5anoteleiauni03D1uni03D5uni03D6franclirapesetaEuroafii61289estimatedpartialdiffproductsummationuni2219radicalinfinityintegralapproxequalnotequallessequalgreaterequallozengeuni02C9uniEFEDuniEFEEuniEFF1uniEFF2uniEFF3uniEFF5uniEFF7AcuteCaronDieresisDieresisAcuteDieresisGraveGraveHungarumlautMacroncyrBrevecyrFlexdblGravecyrbrevecyrflexdblgravedieresisacutedieresisgraveuniF635uniF637uniF638uniF639uniF6DCuniF63AuniF63BuniF63CuniF63DuniF63EuniF63FuniF640uniF641uniF642uniF628uniF643uniF644uniF645uniF646uniF647uniF648uniF649uniF64AuniF64BuniF64CuniF64DuniF64EuniF64FuniF650uniF651uniF652uniF653uniF654uniF655uniF656uniF657uniF658uniF659uniF65AuniF65BuniF65CuniF65DuniF65EuniF65FuniF660uniF629uniF62AuniF62BuniF62CuniF62DuniF661uniF662uniF663uniF664uniF665uniF666uniF667uniF668uniF669uniF66AuniF66BuniF66CuniF62EuniF62FuniF630uniF631uniF632uniF66DuniF66EuniF66FuniF670uniF671uniF672uniF673uniF674uniF675uniF676uniF677uniF678uniF679uniF67AuniF67BuniF67CuniF67DuniF67EuniF67FuniF680uniF681uniF682uniF683uniF684uniF685uniF686uniF687uniF688uniF689uniF68AuniF68BuniF68CuniF68DuniF68EuniF68FuniF690uniF691uniF692uniF693uniF694uniF695uniF696uniF697uniF698uniF699uniF69AuniF69BuniF69CuniF69DuniF69EuniF69FuniF6A0uniF6A1uniF6A2uniF6A3uniF6A4uniF6A5uniF6A6uniF6A7uniF6A8uniF6A9uniF6AAuniF6ABuniF6ACuniF6ADuniF6AEuniF6AFuniF6B0uniF6B1uniF6B2uniF6B3uniF6B4uniF6B5uniF6B6uniF6B7uniF6B8uniF6B9uniF6BAuniF6BBuniF6BCuniF6BDuniF633c_hc_kc_tf_bf_f_bf_f_hf_f_kf_f_tf_hf_jf_f_jf_kf_ts_puniFB06T_hlongs_blongs_hlongs_ilongs_klongs_llongs_longsuniFB05longs_longs_ilongs_longs_la.ende.endm.endn.endr.endK.altR.altk.altcaron.altcommaaccent.altpeseta.altAlphaiotasub.altAlphaiotasubasper.altAlphaiotasubasperacute.altAlphaiotasubaspergrave.altAlphaiotasubaspertilde.altAlphaiotasublenis.altAlphaiotasublenisacute.altAlphaiotasublenisgrave.altAlphaiotasublenistilde.altEtaiotasub.altEtaiotasubasper.altEtaiotasubasperacute.altEtaiotasubaspergrave.altEtaiotasubaspertilde.altEtaiotasublenis.altEtaiotasublenisacute.altEtaiotasublenisgrave.altEtaiotasublenistilde.altOmegaiotasub.altOmegaiotasubasper.altOmegaiotasubasperacute.altOmegaiotasubaspergrave.altOmegaiotasubaspertilde.altOmegaiotasublenis.altOmegaiotasublenisacute.altOmegaiotasublenisgrave.altOmegaiotasublenistilde.altEuro.fittedcent.fittedcolonmonetary.fitteddollar.fittedflorin.fittedfranc.fittedlira.fittednumbersign.fittedsterling.fittedyen.fittedEuro.oldstylecolonmonetary.oldstyleestimated.oldstyleflorin.oldstylefranc.oldstylelira.oldstylenumbersign.oldstylesterling.oldstyleyen.oldstylefranc.taboldstylelira.taboldstyleorn.001orn.002orn.003orn.004orn.005orn.006orn.007orn.008orn.009orn.010orn.011orn.012orn.013orn.014orn.015orn.016orn.017orn.018orn.019orn.020orn.021orn.022orn.023afii10023afii10031afii10022afii10049T_h.caronafii10070afii10196afii10026afii10021afii10846afii10193afii10107afii10024afii10195afii10041afii10037afii10109afii10053afii10045afii10108afii10040afii10104afii10036afii10078afii10074afii10060afii10046afii10052afii10087afii10050afii10145afii10057afii10059afii10146afii10088afii10101afii10054afii10058Rholenisafii10025afii10099afii10068afii10035afii10048afii10089afii10105afii10085afii10020afii10077afii10106afii10019afii10076afii10110afii10100afii10090afii10028afii10095afii10147afii10066afii10098afii10082afii10061afii10103afii10102afii10083afii10027afii10072afii10039afii61352afii10069afii10094afii10038afii10034afii10148afii10032afii10194afii10033afii10075afii10017afii10081afii10056afii10084afii10044afii10030afii10051afii10047afii10018afii10080afii10042afii10071afii10029afii10062afii10065afii10097T_h.commaaccentafii10096afii10079afii10091afii10093afii10064afii10043afii10092uni2215uni021Bafii10073afii10067uni00A0uni021Aafii10086afii10055uni0394uni03BCuni03A9uni00ADCopyright 2000 Adobe Systems Incorporated. All Rights Reserved. U.S. Patent Des. 337,604.Minion is either a registered trademark or a trademark of Adobe Systems Incorporated in the United States and/or other countries.Minion Pro RegularMinion Pro% i WZ5:`v22> % I
/
2
I
o
#3p~U
D
e
!o#]emE %<Jeov~EMfjtFp|,S-AZ0=DK +^&7NQy(/S_dl 5Rk$=Valsz"'-@T_gos{ ) . > N ^ d n v ~ !!!!'!3!?!H!Q!Z!]!c!i!n!s!x!!!!!!!!!!!!!"""#"'"3"?"K"W"c"k"s"{""""""""""""""c&oEr^7 JB@H *W2c~sp&m!1= 4:$kYyywRvzwrZnon?˘iNUddLoLݪ
~}}vywS6vO(Zp^TrǕ؍8x`?NYwUVYWE}zyMhummR~Kfowx}|txcBzuyBpOwTxql[LPҩy}~Bxxhzqlc#T0@9
5/j,X^M8Uruuoquvqiff{bE<H8XUo^bb_rMG'Н=[W}yQSSۚ$P|TzTyT'
ajqyzx||rrpwttozpj`lWHrʥaiqyo
|rqpxt@tpyqjalVHr]yt/m'mDx]pIsn8AgmxpQAz4wv~s}~vstzf|oęgfeoszvwzxu$wny|YgJO-ʆea]>9+ZhchAB_\?#^|m[5v-<<[FL LHHq˂~XxAo4uFabfqaf%f+rrs}ǔcqW "* ڟŇՊvx|po~}wUJN<0o-כtzr[ {"!coч~^o]/6'orsBp0ZlZqRoGt{_Fpq|iiMkTratap`DabuvCICpAϦ{~{lpˇBDDpӐ qoكtYoNU)gI_Z`yӔodžF/INlw71oC
ŸԱȗГnoՆ3$811xrdcQD:0] ;hJjp~djmplXhZfYxnmmyf^#MR:AgszvT]jjZ?_ynZQ{sNHyZdƨ]O틯֯}ޣDyZ{kvumofFMk_VYЄ#ms^@L A_!Z Z|蒯}~rqyg|usqrwgmazԬqbfZBoل5|%69o<3oZMZJuׇ3c T{ddmvrjY_VpŇkrkGpφ}8Fgsmy]pWSy/OBR7WXjfeolw}v84o~}xUGP~72pC
~㿊IK
NϪb98IPq
`y[~XsłI\FL
ދ.R۲vhl_@oۅ8(85oq͗ƫ>(3XOG7]_\i^%"Ba:Jy.}eu}|wzq]is|~ґϐuCDDEp
ؑ~P|xhcMp^},
qkuGuzwv~s}~ust}e{nęgfR5BcH
蠓`
i
`c
v
y
蠚}xsnyvrpyh&T~Y|S|Q4xrqxvrpyhrqVVrm