%PDF-1.6
%
1 0 obj
<>
endobj
2 0 obj
<>stream
Ariadna S. Soto, Ignacio M. Fenoy, Vanesa R. Sanchez, Florencia March, Matías D. Perrone Sibilia, María de los Angeles Aldirico, Mariano S. Picchio, Nadia Arcon, Patricio L. Acosta, Fernando P. Polack, Valentina Martin, Alejandra Goldman
Toxoplasma gondii serine-protease inhibitor-1: A new adjuvant candidate for asthma therapy
www.plosone.org
www.plosone.org
endstream
endobj
3 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 13 0 R/Annots 14 0 R/Contents 15 0 R/TrimBox[0 0 612 792]>>
endobj
14 0 obj
[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 41 0 R 42 0 R]
endobj
16 0 obj
<>/Border[0 0 0]/Dest(Rpone.0187002.ref002)>>
endobj
17 0 obj
<>/Border[0 0 0]/Dest(Rpone.0187002.ref004)>>
endobj
18 0 obj
<>/Border[0 0 0]/Dest(Rpone.0187002.ref005)>>
endobj
19 0 obj
<>/Border[0 0 0]/Dest(Rpone.0187002.ref006)>>
endobj
20 0 obj
<>/Border[0 0 0]/Dest(Rpone.0187002.ref007)>>
endobj
21 0 obj
<>/Border[0 0 0]/Dest(Rpone.0187002.ref008)>>
endobj
22 0 obj
<>/Border[0 0 0]/Dest(Rpone.0187002.ref009)>>
endobj
23 0 obj
<>/Border[0 0 0]/Dest(Rpone.0187002.ref010)>>
endobj
24 0 obj
<>/Border[0 0 0]/Dest(Rpone.0187002.ref011)>>
endobj
25 0 obj
<>/Border[0 0 0]/Dest(Rpone.0187002.ref012)>>
endobj
26 0 obj
<>/Border[0 0 0]/Dest(Rpone.0187002.ref013)>>
endobj
27 0 obj
<>/Border[0 0 0]/Dest(Rpone.0187002.ref014)>>
endobj
28 0 obj
<>/Border[0 0 0]/Dest(Rpone.0187002.ref015)>>
endobj
29 0 obj
<>/Border[0 0 0]/Dest(Rpone.0187002.ref016)>>
endobj
30 0 obj
<>/Border[0 0 0]/Dest(Rpone.0187002.ref017)>>
endobj
31 0 obj
<>/Border[0 0 0]/Dest(Rpone.0187002.ref018)>>
endobj
32 0 obj
<>/Border[0 0 0]/Dest(Rpone.0187002.ref019)>>
endobj
33 0 obj
<>/Border[0 0 0]/Dest(Rpone.0187002.ref021)>>
endobj
34 0 obj
<>/Border[0 0 0]/Dest(Rpone.0187002.ref022)>>
endobj
35 0 obj
<>/Border[0 0 0]/Dest(Rpone.0187002.ref023)>>
endobj
36 0 obj
<>/Border[0 0 0]/Dest(Rpone.0187002.ref024)>>
endobj
37 0 obj
<>/Border[0 0 0]/Dest(Rpone.0187002.ref025)>>
endobj
38 0 obj
<>/Border[0 0 0]/Dest(Rpone.0187002.ref026)>>
endobj
39 0 obj
<>/Border[0 0 0]/Dest(Rpone.0187002.ref027)>>
endobj
40 0 obj
<>/Border[0 0 0]/Dest(Rpone.0187002.ref030)>>
endobj
41 0 obj
<>/Border[0 0 0]/A 43 0 R>>
endobj
43 0 obj
<>
endobj
42 0 obj
<>/Border[0 0 0]/A 44 0 R>>
endobj
44 0 obj
<>
endobj
15 0 obj
[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 68 0 R 69 0 R 70 0 R 71 0 R 72 0 R]
endobj
45 0 obj
<>stream
q
0.83 0.64 0.02 0 k
273.2598 680.315 m
278.022 680.315 l
h
f*
283.1811 680.315 m
287.9433 680.315 l
h
f*
511.3134 654.3496 m
516.0756 654.3496 l
h
f*
480.8126 628.3276 m
485.5748 628.3276 l
h
f*
487.7858 628.3276 m
492.548 628.3276 l
h
f*
203.4142 615.3449 m
208.1764 615.3449 l
h
f*
261.4677 615.3449 m
266.1732 615.3449 l
h
f*
280.4031 563.3008 m
289.8709 563.3008 l
h
f*
292.1386 563.3008 m
301.663 563.3008 l
h
f*
279.9496 537.3354 m
289.474 537.3354 l
h
f*
354.5008 537.3354 m
364.0252 537.3354 l
h
f*
253.1339 485.348 m
262.6016 485.348 l
h
f*
535.4646 485.348 m
544.989 485.348 l
h
f*
403.6535 472.3087 m
413.1213 472.3087 l
h
f*
415.389 472.3087 m
424.9134 472.3087 l
h
f*
244.3465 459.326 m
253.8709 459.326 l
h
f*
334.0913 433.3039 m
343.6157 433.3039 l
h
f*
348.7748 433.3039 m
358.2992 433.3039 l
h
f*
472.5354 433.3039 m
482.0598 433.3039 l
h
f*
366.1228 420.3213 m
375.5906 420.3213 l
h
f*
203.4142 381.3165 m
212.9386 381.3165 l
h
f*
499.9748 381.3165 m
509.4992 381.3165 l
h
f*
428.3717 368.3339 m
437.8961 368.3339 l
h
f*
270.4819 290.3244 m
280.0063 290.3244 l
h
f*
285.1654 290.3244 m
294.6898 290.3244 l
h
f*
0 g
1 j
1 J
0 w
10 0 0 10 200.0125 707.4141 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(treatment)Tj
4.1272 0 Td
(of)Tj
1.0148 0 Td
(allergic)Tj
3.0897 0 Td
(conditions)Tj
4.4731 0 Td
(depend)Tj
3.1804 0 Td
(on)Tj
1.2699 0 Td
(antihistamines)Tj
6.0718 0 Td
(and)Tj
1.7234 0 Td
(anti-inflammatory)Tj
7.6025 0 Td
(agents;)Tj
2.9707 0 Td
(how-)Tj
-35.5235 -1.3039 Td
(ever,)Tj
2.1089 0 Td
(the)Tj
1.457 0 Td
(long)Tj
1.9786 0 Td
(term)Tj
2.126 0 Td
(use)Tj
1.525 0 Td
(of)Tj
1.0034 0 Td
(these)Tj
2.2451 0 Td
(drugs)Tj
2.4661 0 Td
(may)Tj
1.9162 0 Td
(lead)Tj
1.8425 0 Td
(to)Tj
1.0148 0 Td
(the)Tj
1.4627 0 Td
(appearance)Tj
4.7395 0 Td
(of)Tj
1.0034 0 Td
(side)Tj
1.7915 0 Td
(effects)Tj
2.7156 0 Td
(and)Tj
1.7234 0 Td
(the)Tj
1.457 0 Td
(genera-)Tj
-34.5767 -1.2982 Td
(tion)Tj
1.8425 0 Td
(of)Tj
1.0148 0 Td
(resistance)Tj
4.1272 0 Td
([)Tj
0.83 0.64 0.02 0 k
(2)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(4)Tj
0 g
(].)Tj
2.5965 0 Td
(Therefore,)Tj
4.3937 0 Td
(immunotherapy)Tj
6.735 0 Td
(is)Tj
0.8448 0 Td
(currently)Tj
3.8891 0 Td
(an)Tj
1.2019 0 Td
(alternative)Tj
4.422 0 Td
(treatment)Tj
4.1329 0 Td
(to)Tj
-35.2004 -1.2983 Td
(antihistamines,)Tj
6.2985 0 Td
(bronchodilators)Tj
6.6274 0 Td
(and)Tj
1.7291 0 Td
(corticosteroids.)Tj
-13.4588 -1.2983 Td
(It)Tj
0.8617 0 Td
(is)Tj
0.8447 0 Td
(well)Tj
1.8198 0 Td
(known)Tj
3.0047 0 Td
(that)Tj
1.7802 0 Td
(allergy)Tj
2.863 0 Td
(may)Tj
1.9275 0 Td
(be)Tj
1.1509 0 Td
(down)Tj
2.4888 0 Td
(modulated)Tj
4.5297 0 Td
(by)Tj
1.1792 0 Td
(certain)Tj
2.9877 0 Td
(infections)Tj
4.1556 0 Td
([)Tj
0.83 0.64 0.02 0 k
(5)Tj
0 g
(].)Tj
1.5987 0 Td
(The)Tj
1.7858 0 Td
(knowl-)Tj
-34.1742 -1.3039 Td
(edge)Tj
2.0579 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(mechanisms)Tj
5.2101 0 Td
(participating)Tj
5.3291 0 Td
(in)Tj
1.0318 0 Td
(this)Tj
1.6781 0 Td
(process)Tj
3.1804 0 Td
(offered)Tj
3.0501 0 Td
(novel)Tj
2.3981 0 Td
(therapeutic)Tj
4.7338 0 Td
(approaches)Tj
4.7395 0 Td
(for)Tj
-35.892 -1.2982 Td
(allergic)Tj
3.0954 0 Td
(diseases)Tj
3.3788 0 Td
(by)Tj
1.1792 0 Td
(using)Tj
2.3925 0 Td
(immunomodulatory)Tj
8.4018 0 Td
(microbe's)Tj
4.1159 0 Td
(components)Tj
5.176 0 Td
([)Tj
0.83 0.64 0.02 0 k
(6)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(7)Tj
0 g
(].)Tj
2.3017 0 Td
(In)Tj
1.1055 0 Td
(this)Tj
1.6781 0 Td
(context,)Tj
3.4073 0 Td
(we)Tj
-36.2322 -1.2983 Td
([)Tj
0.83 0.64 0.02 0 k
(8)Tj
0 g
(])Tj
1.3719 0 Td
(and)Tj
1.7235 0 Td
(others)Tj
2.7099 0 Td
([)Tj
0.83 0.64 0.02 0 k
(9)Tj
0 g
(])Tj
1.3719 0 Td
(have)Tj
2.0523 0 Td
(previously)Tj
4.3483 0 Td
(shown)Tj
2.846 0 Td
(that)Tj
/F13 1 Tf
1.7745 0 Td
[()97()19()-4()11()10()4()10()6()]TJ
4.9946 0 Td
[( )2()11(\n)6()12()12()]TJ
/F8 1 Tf
2.6532 0 Td
(infection)Tj
3.787 0 Td
(decreases)Tj
3.9629 0 Td
(the)Tj
1.4683 0 Td
(subse-)Tj
-35.0643 -1.3039 Td
(quent)Tj
2.5228 0 Td
(development)Tj
5.4084 0 Td
(of)Tj
1.0148 0 Td
(allergic)Tj
3.1011 0 Td
(lung)Tj
2.0069 0 Td
(inflammation.)Tj
5.9244 0 Td
(These)Tj
2.5682 0 Td
(results)Tj
2.8063 0 Td
(led)Tj
1.4173 0 Td
(us)Tj
1.1111 0 Td
(to)Tj
1.0205 0 Td
(search)Tj
2.7609 0 Td
(for)Tj
1.389 0 Td
(parasite)Tj
-33.0517 -1.2983 Td
(proteins)Tj
3.5149 0 Td
(with)Tj
1.9956 0 Td
(immunomodulatory)Tj
8.4018 0 Td
(properties)Tj
4.2803 0 Td
(that)Tj
1.7745 0 Td
(could)Tj
2.4548 0 Td
(be)Tj
1.1508 0 Td
(used)Tj
2.058 0 Td
(for)Tj
1.3889 0 Td
(allergy)Tj
2.8573 0 Td
(treatments.)Tj
4.7225 0 Td
(The)Tj
/F13 1 Tf
1.7858 0 Td
[()]TJ
/F8 1 Tf
(.)Tj
/F13 1 Tf
-36.3852 -1.2983 Td
[( )2()11(\n)6()12()12()]TJ
/F8 1 Tf
2.6532 0 Td
(protease)Tj
3.5603 0 Td
(inhibitor-1)Tj
4.6034 0 Td
(\(TgPI-1\))Tj
3.702 0 Td
(is)Tj
0.8504 0 Td
(a)Tj
0.652 0 Td
(four)Tj
1.9162 0 Td
(domain)Tj
3.3222 0 Td
(protein)Tj
3.1521 0 Td
(that)Tj
1.7801 0 Td
(belongs)Tj
3.2768 0 Td
(to)Tj
1.0262 0 Td
(Kazal-type)Tj
4.4673 0 Td
(serine)Tj
-34.9622 -1.3039 Td
(protease)Tj
3.5546 0 Td
(inhibitors)Tj
4.1442 0 Td
([)Tj
0.83 0.64 0.02 0 k
(10)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(11)Tj
0 g
(].)Tj
3.2485 0 Td
(Biochemical)Tj
5.142 0 Td
(studies)Tj
2.9877 0 Td
(with)Tj
1.9956 0 Td
(a)Tj
0.6519 0 Td
(recombinant)Tj
5.3688 0 Td
(form)Tj
2.2054 0 Td
(of)Tj
1.0148 0 Td
(this)Tj
1.6781 0 Td
(protein)Tj
3.1521 0 Td
(have)Tj
-35.1437 -1.2982 Td
(shown)Tj
2.8459 0 Td
(its)Tj
1.1452 0 Td
(ability)Tj
2.6986 0 Td
(to)Tj
1.0261 0 Td
(inhibit)Tj
2.9027 0 Td
(a)Tj
0.6519 0 Td
(broad)Tj
2.5682 0 Td
(range)Tj
2.4605 0 Td
(of)Tj
1.0148 0 Td
(serine-proteases,)Tj
6.8881 0 Td
(including)Tj
4.0422 0 Td
(trypsin,)Tj
3.2655 0 Td
(chymotrypsin,)Tj
-31.5097 -1.2983 Td
(neutrophil)Tj
4.456 0 Td
(elastase)Tj
3.1974 0 Td
([)Tj
0.83 0.64 0.02 0 k
(12)Tj
0 g
(])Tj
1.8539 0 Td
(and)Tj
1.7291 0 Td
(subtilisin)Tj
3.8721 0 Td
([)Tj
0.83 0.64 0.02 0 k
(13)Tj
0 g
(].)Tj
2.075 0 Td
(It)Tj
0.8617 0 Td
(has)Tj
1.542 0 Td
(been)Tj
2.1203 0 Td
(reported)Tj
3.6624 0 Td
(that)Tj
1.7744 0 Td
(many)Tj
2.4775 0 Td
(serine)Tj
2.6192 0 Td
(protease)Tj
-32.241 -1.3039 Td
(inhibitors)Tj
4.1385 0 Td
(such)Tj
2.0636 0 Td
(as)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(secretory)Tj
3.8551 0 Td
(leukocyte)Tj
4.0195 0 Td
(protease)Tj
3.5547 0 Td
(inhibitor)Tj
3.7814 0 Td
(\(SLPI\))Tj
2.8119 0 Td
(and)Tj
1.7348 0 Td
(the)Tj
1.4683 0 Td
(serum)Tj
2.7213 0 Td
(protease)Tj
-32.6322 -1.2983 Td
(inhibitor)Tj
/F14 1 Tf
3.7813 0 Td
()Tj
/F8 1 Tf
(1-antitrypsin)Tj
5.9811 0 Td
(\(hAAT\))Tj
3.4072 0 Td
(possess)Tj
3.1125 0 Td
(immunomodulatory)Tj
8.4018 0 Td
(properties.)Tj
4.5014 0 Td
(These)Tj
2.5682 0 Td
(properties)Tj
-31.7535 -1.2982 Td
(include)Tj
3.1804 0 Td
(the)Tj
1.474 0 Td
(inhibition)Tj
4.2236 0 Td
(of)Tj
1.0148 0 Td
(inflammatory)Tj
5.7089 0 Td
(responses)Tj
4.0932 0 Td
(by)Tj
1.1849 0 Td
(preventing)Tj
4.5354 0 Td
(the)Tj
1.4684 0 Td
(activation)Tj
4.1555 0 Td
(of)Tj
1.0148 0 Td
(nuclear)Tj
3.1918 0 Td
(factor)Tj
/F14 1 Tf
-35.2457 -1.2983 Td
()Tj
/F8 1 Tf
(B)Tj
1.3379 0 Td
(\(NF-)Tj
/F14 1 Tf
()Tj
/F8 1 Tf
(B\))Tj
3.634 0 Td
([)Tj
0.83 0.64 0.02 0 k
(14)Tj
0 g
(])Tj
1.8482 0 Td
(or)Tj
1.0998 0 Td
(by)Tj
1.1792 0 Td
(up-regulating)Tj
5.6636 0 Td
(IL-10)Tj
2.3981 0 Td
(and)Tj
1.7348 0 Td
(TGF-)Tj
/F14 1 Tf
()Tj
/F8 1 Tf
2.9083 0 Td
(production)Tj
4.7168 0 Td
(by)Tj
1.1792 0 Td
(macrophages)Tj
5.5049 0 Td
([)Tj
0.83 0.64 0.02 0 k
(15)Tj
0 g
(];)Tj
2.0806 0 Td
(the)Tj
-35.2854 -1.3039 Td
(development)Tj
5.4084 0 Td
(of)Tj
1.0148 0 Td
(antigen-specific)Tj
6.5253 0 Td
(T)Tj
0.8334 0 Td
(regulatory)Tj
4.32 0 Td
(cells)Tj
1.9219 0 Td
([)Tj
0.83 0.64 0.02 0 k
(16)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(17)Tj
0 g
(])Tj
3.0273 0 Td
(and)Tj
1.7292 0 Td
(the)Tj
1.4683 0 Td
(reduction)Tj
4.1159 0 Td
(of)Tj
1.0148 0 Td
(B-lymphocyte)Tj
-31.3793 -1.2983 Td
(responses)Tj
4.0932 0 Td
([)Tj
0.83 0.64 0.02 0 k
(18)Tj
0 g
(].)Tj
-2.897 -1.2983 Td
(In)Tj
1.1111 0 Td
(addition,)Tj
3.8211 0 Td
(it)Tj
0.788 0 Td
(is)Tj
0.8448 0 Td
(known)Tj
3.0047 0 Td
(that)Tj
1.7801 0 Td
(both)Tj
2.058 0 Td
(endogenous)Tj
5.0626 0 Td
(and)Tj
1.7291 0 Td
(exogenous)Tj
4.4504 0 Td
(proteases)Tj
3.9174 0 Td
(play)Tj
1.8709 0 Td
(significant)Tj
-31.6344 -1.3039 Td
(roles)Tj
2.1259 0 Td
(in)Tj
1.0375 0 Td
(asthma)Tj
3.0954 0 Td
(pathophysiology)Tj
6.8088 0 Td
([)Tj
0.83 0.64 0.02 0 k
(19)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(21)Tj
0 g
(].)Tj
3.5489 0 Td
(Mast)Tj
2.2054 0 Td
(cell)Tj
1.559 0 Td
(serine)Tj
2.6136 0 Td
(proteases)Tj
3.9174 0 Td
([)Tj
0.83 0.64 0.02 0 k
(22)Tj
0 g
(],)Tj
2.075 0 Td
(matrix)Tj
2.8799 0 Td
(metalloprotei-)Tj
-31.8668 -1.2982 Td
(nase-9)Tj
2.8119 0 Td
(\(MMP-9\))Tj
4.0705 0 Td
(and)Tj
1.7291 0 Td
(neutrophil)Tj
4.4561 0 Td
(elastase)Tj
3.2031 0 Td
([)Tj
0.83 0.64 0.02 0 k
(23)Tj
0 g
(])Tj
1.8482 0 Td
(showed)Tj
3.2541 0 Td
(to)Tj
1.0262 0 Td
(be)Tj
1.1452 0 Td
(present)Tj
3.1634 0 Td
(in)Tj
1.0375 0 Td
(elevated)Tj
3.4526 0 Td
(levels)Tj
2.3754 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4683 0 Td
(air-)Tj
-36.0791 -1.2983 Td
(ways)Tj
2.1543 0 Td
(of)Tj
1.0148 0 Td
(asthmatic)Tj
4.0818 0 Td
(patients)Tj
3.3676 0 Td
(suggesting)Tj
4.405 0 Td
(an)Tj
1.2019 0 Td
(imbalance)Tj
4.3199 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4683 0 Td
(protease/anti-prot)Tj
7.2624 0 Td
(ease)Tj
1.8595 0 Td
(system.)Tj
3.1634 0 Td
(In)Tj
-35.3364 -1.3039 Td
(this)Tj
1.6724 0 Td
(regard,)Tj
3.0387 0 Td
(it)Tj
0.788 0 Td
(has)Tj
1.5421 0 Td
(been)Tj
2.1203 0 Td
(demonstrated)Tj
5.7599 0 Td
(that)Tj
1.7802 0 Td
(neutrophil)Tj
4.456 0 Td
(elastase)Tj
3.1975 0 Td
(promotes)Tj
4.0251 0 Td
(bronchoconstriction)Tj
-28.3802 -1.2983 Td
([)Tj
0.83 0.64 0.02 0 k
(24)Tj
0 g
(])Tj
1.8481 0 Td
(and)Tj
1.7348 0 Td
(stimulates)Tj
4.252 0 Td
(the)Tj
1.474 0 Td
(secretion)Tj
3.8437 0 Td
(of)Tj
1.0148 0 Td
(mucin5AC)Tj
4.6261 0 Td
(from)Tj
2.2054 0 Td
(airway)Tj
2.8686 0 Td
(epithelial)Tj
3.8721 0 Td
(cells)Tj
1.9162 0 Td
([)Tj
0.83 0.64 0.02 0 k
(25)Tj
0 g
(].)Tj
2.0806 0 Td
(Also,)Tj
2.2394 0 Td
(it)Tj
0.788 0 Td
(has)Tj
-34.7638 -1.2983 Td
(been)Tj
2.1203 0 Td
(shown)Tj
2.8516 0 Td
(that)Tj
1.7745 0 Td
(trypsin)Tj
3.0387 0 Td
(can)Tj
1.6271 0 Td
(activate)Tj
3.2541 0 Td
(human)Tj
3.0784 0 Td
(eosinophils)Tj
4.7509 0 Td
([)Tj
0.83 0.64 0.02 0 k
(26)Tj
0 g
(].)Tj
-21.2994 -1.2982 Td
(Therefore,)Tj
4.3936 0 Td
(targeting)Tj
3.7928 0 Td
(proteolytic)Tj
4.5354 0 Td
(activity)Tj
3.1181 0 Td
(with)Tj
1.9955 0 Td
(inhibitors)Tj
4.1443 0 Td
(could)Tj
2.4491 0 Td
(lead)Tj
1.8538 0 Td
(to)Tj
1.0262 0 Td
(a)Tj
0.6519 0 Td
(reduction)Tj
4.1159 0 Td
(of)Tj
1.0148 0 Td
(prote-)Tj
-34.2876 -1.3039 Td
(ases)Tj
1.7971 0 Td
(induced)Tj
3.4696 0 Td
(inflammatory)Tj
5.7033 0 Td
(diseases.)Tj
3.6056 0 Td
(Moreover,)Tj
4.3993 0 Td
(the)Tj
1.4684 0 Td
(immunomodulating)Tj
8.3508 0 Td
(ability)Tj
2.6929 0 Td
(of)Tj
1.0148 0 Td
(serine)Tj
2.6135 0 Td
(prote-)Tj
-35.1153 -1.2983 Td
(ases)Tj
1.7971 0 Td
(inhibitors)Tj
4.1442 0 Td
(makes)Tj
2.7553 0 Td
(these)Tj
2.2507 0 Td
(proteins)Tj
3.5149 0 Td
(interesting)Tj
4.4957 0 Td
(to)Tj
1.0205 0 Td
(be)Tj
1.1509 0 Td
(studied)Tj
3.1521 0 Td
(as)Tj
1.0148 0 Td
(candidates)Tj
4.4673 0 Td
(for)Tj
1.389 0 Td
(asthma)Tj
-31.1525 -1.2983 Td
(immunotherapy.)Tj
6.9618 0 Td
(In)Tj
1.1055 0 Td
(this)Tj
1.6781 0 Td
(regard,)Tj
3.0387 0 Td
(and)Tj
1.7291 0 Td
(so)Tj
1.0885 0 Td
(far,)Tj
1.5364 0 Td
(the)Tj
1.4683 0 Td
(effect)Tj
2.3641 0 Td
(of)Tj
1.0148 0 Td
(serine)Tj
2.6192 0 Td
(protease)Tj
3.5546 0 Td
(inhibitors)Tj
4.1443 0 Td
(on)Tj
1.2756 0 Td
(allergic)Tj
-33.579 -1.3039 Td
(inflammation)Tj
5.6976 0 Td
(have)Tj
2.0579 0 Td
(mostly)Tj
2.9083 0 Td
(been)Tj
2.1203 0 Td
(studied)Tj
3.1578 0 Td
(in)Tj
1.0318 0 Td
(monotherapy)Tj
5.6296 0 Td
(protocols)Tj
3.9571 0 Td
(by)Tj
1.1849 0 Td
(treating)Tj
3.3278 0 Td
(the)Tj
1.4684 0 Td
(animals)Tj
-32.5415 -1.2982 Td
(without)Tj
3.3278 0 Td
(allergen)Tj
3.3789 0 Td
([)Tj
0.83 0.64 0.02 0 k
(27)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(30)Tj
0 g
(].)Tj
-5.5105 -1.2983 Td
(With)Tj
2.279 0 Td
(this)Tj
1.6781 0 Td
(background)Tj
5.0286 0 Td
(and)Tj
1.7292 0 Td
(facing)Tj
2.6475 0 Td
(the)Tj
1.4683 0 Td
(need)Tj
2.143 0 Td
(to)Tj
1.0261 0 Td
(find)Tj
1.8482 0 Td
(new)Tj
1.8766 0 Td
(molecules)Tj
4.2009 0 Td
(for)Tj
1.3833 0 Td
(the)Tj
1.474 0 Td
(treatment)Tj
4.1329 0 Td
(of)Tj
1.0148 0 Td
(aller-)Tj
-35.1267 -1.3039 Td
(gies,)Tj
1.9615 0 Td
(we)Tj
1.3266 0 Td
(analyzed)Tj
3.702 0 Td
(the)Tj
1.4684 0 Td
(potential)Tj
3.7644 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(serine)Tj
2.6135 0 Td
(protease)Tj
3.5546 0 Td
(inhibitor-1)Tj
4.6092 0 Td
(from)Tj
/F13 1 Tf
2.2053 0 Td
[()]TJ
/F8 1 Tf
(.)Tj
/F13 1 Tf
1.0375 0 Td
[( )2()11(\n)6()12()12()]TJ
/F8 1 Tf
2.6532 0 Td
(for)Tj
1.3889 0 Td
(treating)Tj
-32.7682 -1.2983 Td
(respiratory)Tj
4.5977 0 Td
(allergies.)Tj
3.6794 0 Td
(For)Tj
1.627 0 Td
(this)Tj
1.6725 0 Td
(purpose,)Tj
3.6736 0 Td
(we)Tj
1.3267 0 Td
(studied)Tj
3.1521 0 Td
(its)Tj
1.1451 0 Td
(efficacy)Tj
3.2259 0 Td
(either)Tj
2.5284 0 Td
(administered)Tj
5.4936 0 Td
(alone)Tj
2.3754 0 Td
(or)Tj
1.0998 0 Td
(in)Tj
-35.5972 -1.2983 Td
(combination)Tj
5.3461 0 Td
(with)Tj
1.9955 0 Td
(the)Tj
1.474 0 Td
(allergen.)Tj
3.6 0 Td
(We)Tj
1.6101 0 Td
(found)Tj
2.6192 0 Td
(that)Tj
1.7801 0 Td
(both)Tj
2.058 0 Td
(treatments)Tj
4.4957 0 Td
(with)Tj
2.0012 0 Td
(rTgPI-1)Tj
3.3903 0 Td
(ameliorate)Tj
4.4446 0 Td
(the)Tj
-34.8148 -1.3039 Td
(disease)Tj
3.016 0 Td
(manifestations.)Tj
6.3042 0 Td
(Moreover,)Tj
4.3937 0 Td
(administration)Tj
6.1681 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(serine-protease)Tj
6.3042 0 Td
(inhibitor)Tj
3.7814 0 Td
(concomi-)Tj
-32.4508 -1.2982 Td
(tantly)Tj
2.5001 0 Td
(with)Tj
1.9956 0 Td
(the)Tj
1.4683 0 Td
(allergen)Tj
3.3789 0 Td
(resulted)Tj
3.4015 0 Td
(in)Tj
1.0375 0 Td
(decreased)Tj
4.1329 0 Td
(allergen-specific)Tj
6.7011 0 Td
(T)Tj
0.8277 0 Td
(cell)Tj
1.5647 0 Td
(proliferation)Tj
5.2667 0 Td
(and)Tj
1.7291 0 Td
(expan-)Tj
-34.0041 -1.2983 Td
(sion)Tj
1.9048 0 Td
(of)Tj
1.0148 0 Td
(FoxP3)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 254.5511 204.8314 cm
BT
/F8 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(+)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 261.0708 200.4094 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Tregs.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 170.022 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
(Animals)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 134.9858 cm
BT
/F8 1 Tf
1 TL
-0.01 Tc
0 0 Td
(BALB/c)Tj
3.3165 0 Td
(\(H-2)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 252.2834 139.4645 cm
BT
/F8 1 Tf
1 TL
-0.0133 Tc
0 0 Td
(d)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 256.1952 134.9858 cm
BT
/F8 1 Tf
1 TL
-0.01 Tc
0 0 Td
(\))Tj
0.5499 0 Td
(mice)Tj
2.1316 0 Td
(were)Tj
2.0976 0 Td
(obtained)Tj
3.685 0 Td
(from)Tj
2.1827 0 Td
(the)Tj
1.4513 0 Td
(animal)Tj
2.9367 0 Td
(facilities)Tj
3.4356 0 Td
(of)Tj
1.0034 0 Td
(the)Tj
1.4514 0 Td
(School)Tj
2.8686 0 Td
(of)Tj
1.0035 0 Td
(Veterinary)Tj
4.4447 0 Td
(Sci-)Tj
-34.8602 -1.2982 Td
(ences,)Tj
2.5909 0 Td
(University)Tj
4.3425 0 Td
(of)Tj
0.9978 0 Td
(Buenos)Tj
3.1351 0 Td
(Aires,)Tj
2.5172 0 Td
(Argentina,)Tj
4.4276 0 Td
(and)Tj
1.7122 0 Td
(maintained)Tj
4.7281 0 Td
(in)Tj
1.0205 0 Td
(our)Tj
1.6101 0 Td
(animal)Tj
2.931 0 Td
(facilities)Tj
3.4355 0 Td
(for)Tj
1.372 0 Td
(use)Tj
-34.8205 -1.2983 Td
(throughout)Tj
4.7168 0 Td
(these)Tj
2.2223 0 Td
(experiments.)Tj
5.2951 0 Td
(Mice)Tj
2.1996 0 Td
(were)Tj
2.1033 0 Td
(used)Tj
2.0353 0 Td
(at)Tj
0.9411 0 Td
(the)Tj
1.4513 0 Td
(age)Tj
1.5251 0 Td
(of)Tj
1.0034 0 Td
(6)Tj
0.686 0 Td
(to)Tj
1.0148 0 Td
(8)Tj
0.6916 0 Td
(weeks.)Tj
2.795 0 Td
(All)Tj
1.3776 0 Td
(procedures)Tj
4.6148 0 Td
(requir-)Tj
-34.6731 -1.3039 Td
(ing)Tj
1.4797 0 Td
(animals)Tj
3.2882 0 Td
(were)Tj
2.1032 0 Td
(approved)Tj
3.9231 0 Td
(by)Tj
1.1678 0 Td
(the)Tj
1.4514 0 Td
(Independent)Tj
5.2837 0 Td
(Ethics)Tj
2.6306 0 Td
(Committee)Tj
4.6884 0 Td
(for)Tj
1.3663 0 Td
(the)Tj
1.4514 0 Td
(Care)Tj
2.0862 0 Td
(and)Tj
1.7122 0 Td
(Use)Tj
1.7234 0 Td
(of)Tj
-34.3556 -1.2983 Td
(Experimental)Tj
5.5332 0 Td
(Animals)Tj
3.5375 0 Td
(of)Tj
1.0035 0 Td
(National)Tj
3.6396 0 Td
(University)Tj
4.3427 0 Td
(of)Tj
1.0035 0 Td
(San)Tj
1.661 0 Td
(Martin)Tj
2.9991 0 Td
(\(CICUAE)Tj
4.1726 0 Td
(protocol)Tj
3.5489 0 Td
(ID)Tj
1.2869 0 Td
(#)Tj
0.686 0 Td
(005/16\).)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 478.8283 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Adjuvant)Tj
4.0464 0 Td
(for)Tj
1.3678 0 Td
(asthma)Tj
3.4512 0 Td
(therapy)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.01870)Tj
4.089 0 Td
(02)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
(17)Tj
ET
Q
q
0.83 0.64 0.02 0 k
1 j
1 J
0 w
88.8945 707.6409 m
149.8394 707.6409 l
h
f*
0 g
7.9999 0 0 7.9999 36 708.7181 cm
BT
/F10 1 Tf
1 TL
-0.025 Tc
0 0 Td
(Aires,)Tj
2.3102 0 Td
(Argentina,)Tj
3.9898 0 Td
(\()Tj
0.83 0.64 0.02 0 k
(http://cic.gb)Tj
4.7055 0 Td
(a.gov.ar/)Tj
0 g
(\).)Tj
3.9757 0 Td
(The)Tj
-14.9812 -1.3748 Td
(funders)Tj
3.0472 0 Td
(had)Tj
1.5874 0 Td
(no)Tj
1.1693 0 Td
(role)Tj
1.6087 0 Td
(in)Tj
0.8929 0 Td
(study)Tj
2.2607 0 Td
(design,)Tj
2.8984 0 Td
(data)Tj
1.793 0 Td
(collection)Tj
-15.2576 -1.3748 Td
(and)Tj
1.5874 0 Td
(analysis,)Tj
3.4087 0 Td
(decision)Tj
3.2953 0 Td
(to)Tj
0.9496 0 Td
(publish,)Tj
3.1464 0 Td
(or)Tj
0.9993 0 Td
(preparation)Tj
4.4362 0 Td
(of)Tj
-17.8229 -1.3748 Td
(the)Tj
1.3677 0 Td
(manuscript.)Tj
/F9 1 Tf
-1.3677 -2.126 Td
(Competing)Tj
4.3795 0 Td
(interests)Tj
3.3307 0 Td
(:)Tj
/F10 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 -1.3748 Td
(that)Tj
1.6228 0 Td
(no)Tj
1.1693 0 Td
(competing)Tj
4.1599 0 Td
(interests)Tj
ET
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
endstream
endobj
68 0 obj
<>stream
endstream
endobj
69 0 obj
<>stream
endstream
endobj
70 0 obj
<>stream
endstream
endobj
71 0 obj
<>stream
endstream
endobj
72 0 obj
<>stream
BT
10.3394 -7.6252 Td
(exist.)Tj
ET
Q
endstream
endobj
73 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 13 0 R/Annots 75 0 R/Contents 76 0 R/TrimBox[0 0 612 792]>>
endobj
75 0 obj
[77 0 R 78 0 R 79 0 R 80 0 R 81 0 R 82 0 R]
endobj
77 0 obj
<>/Border[0 0 0]/Dest(Rpone.0187002.ref010)>>
endobj
78 0 obj
<>/Border[0 0 0]/Dest(Rpone.0187002.ref010)>>
endobj
79 0 obj
<>/Border[0 0 0]/Dest(Rpone.0187002.ref031)>>
endobj
80 0 obj
<>/Border[0 0 0]/Dest(Rpone.0187002.ref032)>>
endobj
81 0 obj
<>/Border[0 0 0]/Dest(Rpone.0187002.ref010)>>
endobj
82 0 obj
<>/Border[0 0 0]/A 83 0 R>>
endobj
83 0 obj
<>
endobj
76 0 obj
[84 0 R 85 0 R 86 0 R 87 0 R 88 0 R 89 0 R 90 0 R 91 0 R]
endobj
84 0 obj
<>stream
q
0.83 0.64 0.02 0 k
535.3512 688.0252 m
544.5354 688.0252 l
h
f*
242.3055 610.0157 m
251.4898 610.0157 l
h
f*
253.5874 610.0157 m
262.8283 610.0157 l
h
f*
264.926 610.0157 m
274.1102 610.0157 l
h
f*
409.3795 244.9701 m
418.9039 244.9701 l
h
f*
0 g
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 706.0535 cm
BT
/F0 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Expression)Tj
5.1071 0 Td
(and)Tj
1.8661 0 Td
(purification)Tj
4.989 0 Td
(of)Tj
1.0442 0 Td
(the)Tj
1.5968 0 Td
(recombinant)Tj
5.6552 0 Td
(protein)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 689.1023 cm
BT
/F8 1 Tf
1 TL
-0.02 Tc
0 0 Td
(The)Tj
1.7347 0 Td
(recombinant)Tj
5.1931 0 Td
(TgPI-1)Tj
2.9253 0 Td
(protein)Tj
3.0387 0 Td
(\(rTgPI-1\))Tj
3.9288 0 Td
(was)Tj
1.6498 0 Td
(previously)Tj
4.1952 0 Td
(generated)Tj
3.9912 0 Td
(by)Tj
1.1508 0 Td
(Pszenny)Tj
3.4129 0 Td
(et)Tj
0.9128 0 Td
(al.)Tj
1.0771 0 Td
([)Tj
0.83 0.64 0.02 0 k
(10)Tj
0 g
(].)Tj
1.9956 0 Td
(The)Tj
-35.206 -1.3039 Td
(rTgPI-1)Tj
3.2824 0 Td
(coding)Tj
2.863 0 Td
(region)Tj
2.7043 0 Td
(of)Tj
0.9807 0 Td
(the)Tj
1.423 0 Td
(mature)Tj
2.9991 0 Td
(protein)Tj
3.0387 0 Td
(\(from)Tj
2.4661 0 Td
(residue)Tj
3.0104 0 Td
(25)Tj
1.1395 0 Td
(to)Tj
0.9978 0 Td
(the)Tj
1.4173 0 Td
(end,)Tj
1.8822 0 Td
(residue)Tj
3.0104 0 Td
(294\))Tj
1.9218 0 Td
(was)Tj
1.6498 0 Td
(cloned)Tj
-34.7865 -1.2982 Td
(into)Tj
1.7744 0 Td
(the)Tj
1.423 0 Td
(BamHI)Tj
3.0784 0 Td
(and)Tj
1.6838 0 Td
(KpnI)Tj
2.2393 0 Td
(restriction)Tj
4.1783 0 Td
(sites)Tj
1.8538 0 Td
(of)Tj
0.9808 0 Td
(the)Tj
1.423 0 Td
(pQE30)Tj
2.9253 0 Td
(expression)Tj
4.303 0 Td
(vector,)Tj
2.8119 0 Td
(which)Tj
2.5682 0 Td
(produces)Tj
3.7531 0 Td
(a)Tj
-34.9963 -1.2983 Td
(recombinant)Tj
5.193 0 Td
(protein)Tj
3.0387 0 Td
(with)Tj
1.9332 0 Td
(a)Tj
0.6407 0 Td
(6x-His)Tj
2.8119 0 Td
(tag)Tj
1.3663 0 Td
(at)Tj
0.9184 0 Td
(the)Tj
1.423 0 Td
(N-terminus)Tj
4.7678 0 Td
(\(rTgPI-1\).)Tj
4.1386 0 Td
(The)Tj
1.7291 0 Td
(recombinant)Tj
5.1931 0 Td
(protein)Tj
-33.1538 -1.3039 Td
(includes)Tj
3.4185 0 Td
(the)Tj
1.4173 0 Td
(four)Tj
1.8539 0 Td
(kazal-type)Tj
4.1272 0 Td
(domains.)Tj
/F13 1 Tf
3.7814 0 Td
[(\r)-4()-3()13()6()2()-9()4()13()18()4()]TJ
4.4503 0 Td
[()7()10()12()]TJ
/F8 1 Tf
1.4967 0 Td
(M15)Tj
2.0183 0 Td
(transformed)Tj
4.9946 0 Td
(with)Tj
1.9332 0 Td
(plasmid)Tj
3.2768 0 Td
(pQE30-)Tj
-32.7682 -1.2983 Td
(TgPI-1)Tj
2.9253 0 Td
(was)Tj
1.6497 0 Td
(kindly)Tj
2.6646 0 Td
(provided)Tj
3.6907 0 Td
(by)Tj
1.1508 0 Td
(Dr.)Tj
1.5024 0 Td
(Angel)Tj
2.5058 0 Td
(\(IIB-INTECH,)Tj
5.896 0 Td
(UNSAM\).)Tj
4.1953 0 Td
(For)Tj
1.5817 0 Td
(expression,)Tj
4.5127 0 Td
(as)Tj
0.9808 0 Td
(previously)Tj
-33.2558 -1.2982 Td
(described)Tj
3.9061 0 Td
([)Tj
0.83 0.64 0.02 0 k
(10)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(31)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(32)Tj
0 g
(],)Tj
4.2576 0 Td
(a)Tj
0.6349 0 Td
(single)Tj
2.4378 0 Td
(colony)Tj
2.812 0 Td
(was)Tj
1.6497 0 Td
(grown)Tj
2.7156 0 Td
(overnight)Tj
3.9401 0 Td
(at)Tj
0.9184 0 Td
(37C)Tj
2.1657 0 Td
(in)Tj
1.0035 0 Td
(Luria-Bertani)Tj
5.4198 0 Td
(broth)Tj
2.3527 0 Td
(supple-)Tj
-34.2139 -1.304 Td
(mented)Tj
3.1634 0 Td
(with)Tj
1.9332 0 Td
(ampicillin)Tj
4.0989 0 Td
(\(100)Tj
/F15 1 Tf
1.9219 0 Td
[()]TJ
/F8 1 Tf
(g/ml\))Tj
2.8346 0 Td
(and)Tj
1.6781 0 Td
(kanamycin)Tj
4.5014 0 Td
(\(50)Tj
/F15 1 Tf
1.4683 0 Td
[()]TJ
/F8 1 Tf
(g/ml\),)Tj
3.0387 0 Td
(diluted)Tj
2.9254 0 Td
(ten)Tj
1.4456 0 Td
(times)Tj
2.3074 0 Td
(and)Tj
1.6838 0 Td
(grown)Tj
2.7156 0 Td
(at)Tj
-35.7163 -1.2982 Td
(37C)Tj
2.1599 0 Td
(until)Tj
2.0296 0 Td
(OD600nm)Tj
4.388 0 Td
(=)Tj
0.7824 0 Td
(0.4.)Tj
1.559 0 Td
(rTgPI-1)Tj
3.2825 0 Td
(expression)Tj
4.303 0 Td
(was)Tj
1.6498 0 Td
(induced)Tj
3.3562 0 Td
(by)Tj
1.1508 0 Td
(the)Tj
1.4173 0 Td
(addition)Tj
3.4696 0 Td
(of)Tj
0.9865 0 Td
(isopropyl-)Tj
/F14 1 Tf
()Tj
/F8 1 Tf
(-d-)Tj
-30.5346 -1.2983 Td
(thiogalactopyranoside)Tj
8.7023 0 Td
(at)Tj
0.924 0 Td
(final)Tj
1.9219 0 Td
(concentration)Tj
5.6126 0 Td
(of)Tj
0.9808 0 Td
(1)Tj
0.6803 0 Td
(mM.)Tj
2.1089 0 Td
(After)Tj
2.2054 0 Td
(3)Tj
0.6803 0 Td
(h)Tj
0.7313 0 Td
(of)Tj
0.9808 0 Td
(growth,)Tj
3.1918 0 Td
(cells)Tj
1.8368 0 Td
(were)Tj
2.058 0 Td
(pelleted)Tj
3.1974 0 Td
(and)Tj
-35.8126 -1.2983 Td
(resuspended)Tj
5.0569 0 Td
(in)Tj
1.0035 0 Td
(lysis)Tj
1.8312 0 Td
(buffer)Tj
2.5284 0 Td
(\(8M)Tj
1.8766 0 Td
(Urea;)Tj
2.3357 0 Td
(20)Tj
1.1395 0 Td
(mM)Tj
1.8992 0 Td
(NaH)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 395.6031 557.4047 cm
BT
/F8 1 Tf
1 TL
-0.0266 Tc
0 0 Td
(2)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 399.0047 559.1055 cm
BT
/F8 1 Tf
1 TL
-0.02 Tc
0 0 Td
(PO)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 411.7606 557.4047 cm
BT
/F8 1 Tf
1 TL
-0.0266 Tc
0 0 Td
(4)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 415.1622 559.1055 cm
BT
/F8 1 Tf
1 TL
-0.02 Tc
0 0 Td
(;)Tj
0.4251 0 Td
(300)Tj
1.5988 0 Td
(mM)Tj
1.9048 0 Td
(NaCl;)Tj
2.4435 0 Td
(10)Tj
1.1395 0 Td
(mM)Tj
1.8992 0 Td
(imidazole;)Tj
4.1896 0 Td
(pH)Tj
-35.1153 -1.3039 Td
(7.47.6\).)Tj
3.5093 0 Td
(Cells)Tj
2.0806 0 Td
(were)Tj
2.058 0 Td
(lysed)Tj
2.1543 0 Td
(on)Tj
1.2415 0 Td
(ice)Tj
1.287 0 Td
(by)Tj
1.1508 0 Td
(sonication)Tj
4.2236 0 Td
(and)Tj
1.6838 0 Td
(centrifuged)Tj
4.609 0 Td
(at)Tj
0.9184 0 Td
(10,000)Tj
/F15 1 Tf
[()]TJ
/F8 1 Tf
(g)Tj
3.7304 0 Td
(at)Tj
0.9184 0 Td
(4C)Tj
1.7064 0 Td
(for)Tj
1.338 0 Td
(20)Tj
1.1395 0 Td
(min)Tj
1.8028 0 Td
(to)Tj
-35.5518 -1.2982 Td
(prepare)Tj
3.1635 0 Td
(a)Tj
0.6406 0 Td
(supernatant.)Tj
5.0173 0 Td
(The)Tj
1.7348 0 Td
(supernatant)Tj
4.8018 0 Td
(was)Tj
1.6555 0 Td
(loaded)Tj
2.7892 0 Td
(onto)Tj
2.0182 0 Td
(the)Tj
1.4173 0 Td
(Ni)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 442.148 537.5055 cm
BT
/F8 1 Tf
1 TL
-0.0266 Tc
0 0 Td
(+2)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 449.6881 533.0834 cm
BT
/F8 1 Tf
1 TL
-0.02 Tc
0 0 Td
(-nitriloacetic)Tj
5.125 0 Td
(acid)Tj
1.8084 0 Td
(resin)Tj
2.109 0 Td
(affinity)Tj
-34.0098 -1.2982 Td
(column)Tj
3.1975 0 Td
(\(GE)Tj
1.7972 0 Td
(Healthcare)Tj
4.405 0 Td
(Life)Tj
1.6781 0 Td
(Sciences\),)Tj
3.9685 0 Td
(previously)Tj
4.1895 0 Td
(equilibrated)Tj
4.8302 0 Td
(with)Tj
1.9332 0 Td
(lysis)Tj
1.8311 0 Td
(buffer.)Tj
2.7383 0 Td
(The)Tj
1.7348 0 Td
(column)Tj
3.1974 0 Td
(was)Tj
-35.5008 -1.3039 Td
(then)Tj
1.9503 0 Td
(washed)Tj
3.084 0 Td
(with)Tj
1.9333 0 Td
(10)Tj
1.1395 0 Td
(volumes)Tj
3.4469 0 Td
(of)Tj
0.9864 0 Td
(wash)Tj
2.16 0 Td
(buffer)Tj
2.5285 0 Td
(\(20)Tj
1.4627 0 Td
(mM)Tj
1.9049 0 Td
(NaH)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 424.8566 505.4173 cm
BT
/F8 1 Tf
1 TL
-0.0266 Tc
0 0 Td
(2)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 428.2582 507.0614 cm
BT
/F8 1 Tf
1 TL
-0.02 Tc
0 0 Td
(PO)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 441.0141 505.4173 cm
BT
/F8 1 Tf
1 TL
-0.0266 Tc
0 0 Td
(4)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 444.4157 507.0614 cm
BT
/F8 1 Tf
1 TL
-0.02 Tc
0 0 Td
(;)Tj
0.4251 0 Td
(0.5)Tj
1.3493 0 Td
(M)Tj
1.0999 0 Td
(NaCl;)Tj
2.4434 0 Td
(20)Tj
1.1395 0 Td
(mM)Tj
1.8992 0 Td
(imidazole;)Tj
-32.7965 -1.2982 Td
(pH)Tj
1.474 0 Td
(7.4\))Tj
1.6724 0 Td
(and)Tj
1.6781 0 Td
(eluted)Tj
2.5739 0 Td
(with)Tj
1.9332 0 Td
(elution)Tj
2.9253 0 Td
(buffer)Tj
2.5285 0 Td
(\(20)Tj
1.4627 0 Td
(mM)Tj
1.9048 0 Td
(NaH)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 400.422 492.4346 cm
BT
/F8 1 Tf
1 TL
-0.0266 Tc
0 0 Td
(2)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 403.8236 494.0787 cm
BT
/F8 1 Tf
1 TL
-0.02 Tc
0 0 Td
(PO)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 416.5795 492.4346 cm
BT
/F8 1 Tf
1 TL
-0.0266 Tc
0 0 Td
(4)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 419.9811 494.0787 cm
BT
/F8 1 Tf
1 TL
-0.02 Tc
0 0 Td
(;)Tj
0.4251 0 Td
(0.5M)Tj
2.2281 0 Td
(NaCl;)Tj
2.4434 0 Td
(250)Tj
1.5987 0 Td
(mM)Tj
1.8992 0 Td
(imidazole;)Tj
4.1953 0 Td
(pH)Tj
-34.7865 -1.2982 Td
(7.4\).)Tj
1.8822 0 Td
(The)Tj
1.7348 0 Td
(purified)Tj
3.2825 0 Td
(recombinant)Tj
5.1931 0 Td
(protein)Tj
3.0387 0 Td
(was)Tj
1.6497 0 Td
(quantitated)Tj
4.6091 0 Td
(by)Tj
1.1508 0 Td
(Bradford's)Tj
4.2406 0 Td
(method.)Tj
-0.004 Tc
-25.5852 -1.3039 Td
(Before)Tj
2.8176 0 Td
(mouse)Tj
2.8573 0 Td
(treatment,)Tj
4.3596 0 Td
(rTgPI-1)Tj
3.3959 0 Td
(was)Tj
1.6951 0 Td
(dialyzed)Tj
3.515 0 Td
(against)Tj
3.0272 0 Td
(PBS)Tj
1.8369 0 Td
(and)Tj
1.7291 0 Td
(endotoxins)Tj
4.6715 0 Td
(were)Tj
2.1259 0 Td
(removed)Tj
-33.2274 -1.2983 Td
(with)Tj
1.9956 0 Td
(Detoxi-Gel)Tj
/F15 1 Tf
[()]TJ
/F8 1 Tf
5.108 0 Td
(Endotoxin)Tj
4.4617 0 Td
(Removing)Tj
4.3257 0 Td
(Columns)Tj
3.8947 0 Td
(\(Thermo)Tj
3.8153 0 Td
(Fisher)Tj
2.6986 0 Td
(Scientific,)Tj
4.1329 0 Td
(Pierce)Tj
2.6872 0 Td
(Biotech-)Tj
-33.1197 -1.2983 Td
(nology\),)Tj
3.515 0 Td
(filtered)Tj
3.0614 0 Td
(throughout)Tj
4.7792 0 Td
(a)Tj
0.6576 0 Td
(0.22)Tj
/F15 1 Tf
1.8708 0 Td
[()]TJ
/F8 1 Tf
(m-pore)Tj
3.7134 0 Td
(membrane)Tj
4.5693 0 Td
(and)Tj
1.7292 0 Td
(stored)Tj
2.7099 0 Td
(at)Tj
/F15 1 Tf
0.9524 0 Td
[()]TJ
/F8 1 Tf
(80C.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 413.0645 cm
BT
/F0 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Western)Tj
3.9118 0 Td
(blot)Tj
1.8095 0 Td
(analysis)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 396.0566 cm
BT
/F8 1 Tf
1 TL
-0.02 Tc
0 0 Td
(For)Tj
1.576 0 Td
(Western)Tj
3.4979 0 Td
(blot)Tj
1.7178 0 Td
(analysis,)Tj
3.4072 0 Td
(purified)Tj
3.2825 0 Td
(protein)Tj
3.0388 0 Td
(was)Tj
1.6554 0 Td
(incubated)Tj
4.0308 0 Td
(at)Tj
0.9184 0 Td
(100C)Tj
2.6249 0 Td
(for)Tj
1.338 0 Td
(5)Tj
0.6803 0 Td
(min)Tj
1.8085 0 Td
(in)Tj
1.0034 0 Td
(loading)Tj
3.1011 0 Td
(buffer,)Tj
-33.681 -1.2982 Td
(separated)Tj
3.8664 0 Td
(by)Tj
1.1508 0 Td
(SDS-PAGE)Tj
4.6545 0 Td
(\(12%)Tj
2.2053 0 Td
(gel\))Tj
1.6328 0 Td
(and)Tj
1.6838 0 Td
(transferred)Tj
4.4617 0 Td
(onto)Tj
2.0125 0 Td
(PVDF)Tj
2.6759 0 Td
(membrane)Tj
4.4391 0 Td
(\(GE\))Tj
2.1203 0 Td
(using)Tj
2.313 0 Td
(an)Tj
1.1679 0 Td
(Electro-)Tj
-34.384 -1.3039 Td
(transfer)Tj
3.1861 0 Td
(unit)Tj
1.7971 0 Td
(\(Bio-Rad\).)Tj
4.252 0 Td
(The)Tj
1.7348 0 Td
(membranes)Tj
4.7848 0 Td
(were)Tj
2.058 0 Td
(sequentially)Tj
4.7678 0 Td
(incubated)Tj
4.0365 0 Td
(with)Tj
1.9332 0 Td
(mouse)Tj
2.778 0 Td
(polyclonal)Tj
4.1895 0 Td
(anti-)Tj
-35.5178 -1.2983 Td
(rTgPI-1)Tj
3.2824 0 Td
(antibody)Tj
3.634 0 Td
(\(1:1000\))Tj
3.3732 0 Td
(or)Tj
1.0659 0 Td
(anti-Histidine)Tj
5.6239 0 Td
(\(1:3000;)Tj
3.2598 0 Td
(Sigma\))Tj
2.931 0 Td
(and)Tj
1.6781 0 Td
(alkaline)Tj
3.1918 0 Td
(phosphatase)Tj
4.9492 0 Td
(conjugated)Tj
-32.9893 -1.2983 Td
(goat)Tj
1.8595 0 Td
(anti-mouse)Tj
4.5977 0 Td
(IgG)Tj
1.6895 0 Td
(\(1:5000;)Tj
3.2655 0 Td
(Sigma\).)Tj
3.1351 0 Td
(After)Tj
2.2053 0 Td
(washing,)Tj
3.6056 0 Td
(the)Tj
1.4174 0 Td
(reaction)Tj
3.3675 0 Td
(was)Tj
1.6498 0 Td
(developed)Tj
4.1272 0 Td
(by)Tj
1.1508 0 Td
(the)Tj
1.423 0 Td
(addition)Tj
-33.4939 -1.3039 Td
(of)Tj
0.9807 0 Td
(nitroblue)Tj
3.7758 0 Td
(tetrazolium/5-bromo-4-chloro-3)Tj
12.58 0 Td
(-indolyl)Tj
3.2372 0 Td
(phosphate)Tj
4.1896 0 Td
(\(NBT/BCIP\))Tj
5.142 0 Td
(substrate.)Tj
3.8664 0 Td
(PageRu-)Tj
-33.7717 -1.2982 Td
(ler)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 209.9338 322.5259 cm
BT
/F8 1 Tf
1 TL
-0.0266 Tc
0 0 Td
(TM)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 223.0866 318.0472 cm
BT
/F8 1 Tf
1 TL
-0.02 Tc
0 0 Td
(Prestained)Tj
4.2746 0 Td
(Protein)Tj
3.0784 0 Td
(Ladder)Tj
2.948 0 Td
(\(Thermo)Tj
3.7077 0 Td
(Scientific\))Tj
4.0705 0 Td
(was)Tj
1.6498 0 Td
(used)Tj
1.9955 0 Td
(as)Tj
0.9808 0 Td
(molecular)Tj
4.0762 0 Td
(marker.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 289.0204 cm
BT
/F0 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Trypsin-inhibitory)Tj
7.7339 0 Td
(activity)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 272.0125 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Trypsin-inhibitory)Tj
7.7158 0 Td
(activity)Tj
3.1181 0 Td
(of)Tj
1.0148 0 Td
(rTgPI-1)Tj
3.3959 0 Td
(was)Tj
1.6951 0 Td
(checked)Tj
3.4696 0 Td
(before)Tj
2.7382 0 Td
(mouse)Tj
2.8573 0 Td
(treatment)Tj
4.1386 0 Td
(by)Tj
1.1792 0 Td
(12.5%)Tj
-31.3226 -1.2982 Td
(SDS-PAGE)Tj
4.7848 0 Td
(in)Tj
1.0375 0 Td
(0.15%)Tj
2.6248 0 Td
(gelatin)Tj
2.9084 0 Td
(containing)Tj
4.524 0 Td
(gels,)Tj
1.9446 0 Td
(without)Tj
3.3278 0 Td
(prior)Tj
2.2564 0 Td
(reduction)Tj
4.1102 0 Td
(and)Tj
1.7348 0 Td
(boiling,)Tj
3.2485 0 Td
(a)Tj
0.6576 0 Td
(technique)Tj
-33.1594 -1.2983 Td
(commonly)Tj
4.5467 0 Td
(used)Tj
2.0579 0 Td
(for)Tj
1.389 0 Td
(detection)Tj
3.9345 0 Td
(of)Tj
1.0148 0 Td
(proteolytic)Tj
4.5354 0 Td
(activity)Tj
3.1181 0 Td
([)Tj
0.83 0.64 0.02 0 k
(10)Tj
0 g
(].)Tj
2.0749 0 Td
(Porcine)Tj
3.3222 0 Td
(trypsin)Tj
3.0387 0 Td
(\(50)Tj
1.508 0 Td
(ng\))Tj
1.5761 0 Td
(\(Sigma-)Tj
-32.1163 -1.3039 Td
(Aldrich\))Tj
3.6056 0 Td
(was)Tj
1.7008 0 Td
(incubated)Tj
4.1782 0 Td
(with)Tj
1.9956 0 Td
(or)Tj
1.0998 0 Td
(without)Tj
3.3279 0 Td
(1)Tj
/F15 1 Tf
0.6973 0 Td
[()]TJ
/F8 1 Tf
(g)Tj
1.1905 0 Td
(of)Tj
1.0148 0 Td
(rTgPI-1)Tj
3.3959 0 Td
(in)Tj
1.0318 0 Td
(the)Tj
1.474 0 Td
(activity)Tj
3.1125 0 Td
(buffer)Tj
2.6305 0 Td
(\(25)Tj
1.508 0 Td
(mM)Tj
1.9332 0 Td
(Tris)Tj
-33.8964 -1.2983 Td
(HCl,)Tj
2.1203 0 Td
(pH)Tj
1.508 0 Td
(7.2,)Tj
1.6214 0 Td
(50)Tj
1.1678 0 Td
(mM)Tj
1.9333 0 Td
(NaCl\))Tj
2.6418 0 Td
(at)Tj
0.9525 0 Td
(37C)Tj
2.228 0 Td
(for)Tj
1.3833 0 Td
(15)Tj
1.1735 0 Td
(min)Tj
1.8539 0 Td
(and)Tj
1.7291 0 Td
(then)Tj
2.0182 0 Td
(subjected)Tj
3.9685 0 Td
(to)Tj
1.0262 0 Td
(electrophoresis.)Tj
6.4743 0 Td
(The)Tj
1.7801 0 Td
(gel)Tj
-35.5802 -1.2982 Td
(was)Tj
1.6894 0 Td
(washed)Tj
3.1748 0 Td
(twice)Tj
2.3074 0 Td
(with)Tj
1.9899 0 Td
(0.1%)Tj
2.1486 0 Td
(Triton)Tj
2.812 0 Td
(X-100,)Tj
2.8686 0 Td
(20)Tj
1.1679 0 Td
(min)Tj
1.8482 0 Td
(each,)Tj
2.245 0 Td
(incubated)Tj
4.1726 0 Td
(at)Tj
0.941 0 Td
(37C)Tj
2.2224 0 Td
(in)Tj
1.0261 0 Td
(the)Tj
1.4627 0 Td
(activity)Tj
3.1124 0 Td
(buffer)Tj
-35.189 -1.3039 Td
(overnight)Tj
4.0818 0 Td
(and)Tj
1.7291 0 Td
(stained)Tj
3.0841 0 Td
(with)Tj
1.9956 0 Td
(Coomassie)Tj
4.5637 0 Td
(Brilliant)Tj
3.4753 0 Td
(Blue)Tj
2.0012 0 Td
(R-250.)Tj
2.8403 0 Td
(The)Tj
1.7859 0 Td
(gelatinase)Tj
4.1215 0 Td
(activity)Tj
3.1181 0 Td
(was)Tj
1.6951 0 Td
(visual-)Tj
-34.4917 -1.2983 Td
(ized)Tj
1.8481 0 Td
(as)Tj
1.0148 0 Td
(white)Tj
2.4208 0 Td
(bands)Tj
2.6022 0 Td
(on)Tj
1.2756 0 Td
(a)Tj
0.6519 0 Td
(blue)Tj
1.9219 0 Td
(background,)Tj
5.2554 0 Td
(which)Tj
2.6532 0 Td
(represented)Tj
4.9096 0 Td
(areas)Tj
2.2394 0 Td
(of)Tj
1.0147 0 Td
(proteolysis.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 151.9937 cm
BT
/F0 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Experimental)Tj
5.9858 0 Td
(protocol)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 134.9858 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Sensitization)Tj
5.3291 0 Td
(was)Tj
1.6951 0 Td
(achieved)Tj
3.702 0 Td
(by)Tj
1.1849 0 Td
(two)Tj
1.7064 0 Td
(intraperitoneal)Tj
6.1795 0 Td
(injections)Tj
4.1215 0 Td
(of)Tj
1.0148 0 Td
(0.2)Tj
1.3947 0 Td
(ml)Tj
1.2869 0 Td
(PBS)Tj
1.8312 0 Td
(containing)Tj
4.5297 0 Td
(chicken)Tj
-33.9758 -1.2982 Td
(egg)Tj
1.5703 0 Td
(white)Tj
2.4208 0 Td
(albumin)Tj
3.5716 0 Td
(\(OVA\))Tj
3.0274 0 Td
(\(grade)Tj
2.7836 0 Td
(V)Tj
0.9128 0 Td
(Sigma-Aldrich\))Tj
6.4176 0 Td
(\(20)Tj
/F15 1 Tf
1.5137 0 Td
[()]TJ
/F8 1 Tf
(g\))Tj
1.5307 0 Td
(and)Tj
1.7291 0 Td
(alum)Tj
2.2507 0 Td
(\(2)Tj
1.0318 0 Td
(mg\))Tj
1.8482 0 Td
(one)Tj
1.7007 0 Td
(week)Tj
2.2451 0 Td
(apart.)Tj
-34.5541 -1.2983 Td
(One)Tj
1.9388 0 Td
(week)Tj
2.2451 0 Td
(later,)Tj
2.2223 0 Td
(mice)Tj
2.1487 0 Td
(were)Tj
2.1259 0 Td
(exposed)Tj
3.4469 0 Td
(to)Tj
1.0205 0 Td
(aerosols)Tj
3.4356 0 Td
(of)Tj
1.0148 0 Td
(allergen)Tj
3.3732 0 Td
(\(3%)Tj
1.7971 0 Td
(\(w/v\)\))Tj
2.7099 0 Td
(OVA)Tj
2.3414 0 Td
(in)Tj
1.0375 0 Td
(PBS)Tj
1.8312 0 Td
(for)Tj
1.3889 0 Td
(20)Tj
1.1736 0 Td
(min)Tj
-35.2514 -1.3039 Td
(on)Tj
1.2755 0 Td
(3)Tj
0.6917 0 Td
(consecutive)Tj
4.8812 0 Td
(days.)Tj
2.2224 0 Td
(Aerosol)Tj
3.3221 0 Td
(exposure)Tj
3.8155 0 Td
(was)Tj
1.6951 0 Td
(performed)Tj
4.473 0 Td
(within)Tj
2.812 0 Td
(individual)Tj
4.2859 0 Td
(compartments)Tj
6.0434 0 Td
(of)Tj
1.0148 0 Td
(a)Tj
-36.5326 -1.2983 Td
(mouse)Tj
2.8573 0 Td
(pie)Tj
1.4286 0 Td
(chamber)Tj
3.7247 0 Td
(using)Tj
2.3924 0 Td
(a)Tj
0.652 0 Td
(nebulizer)Tj
3.9458 0 Td
(\(SAN-UP,)Tj
4.3313 0 Td
(Argentina,)Tj
4.4844 0 Td
(OVA)Tj
2.3471 0 Td
(solution)Tj
3.4809 0 Td
(flux)Tj
1.7461 0 Td
(0.33)Tj
1.8765 0 Td
(ml/min)Tj
3.2485 0 Td
(in)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 478.8283 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Adjuvant)Tj
4.0464 0 Td
(for)Tj
1.3678 0 Td
(asthma)Tj
3.4512 0 Td
(therapy)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.01870)Tj
4.089 0 Td
(02)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
85 0 obj
<>stream
endstream
endobj
86 0 obj
<>stream
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
BT
66.402 0 Td
(17)Tj
ET
Q
endstream
endobj
92 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 13 0 R/Annots 96 0 R/Contents 97 0 R/TrimBox[0 0 612 792]>>
endobj
95 0 obj
<>stream
x1%uIHDzp2F#
R#A'M XY,ȉ x$6v0`dD*2y⪙$f
rLL@&147?Z^VU:{9~;Ϯ^vUO҉xzt⽥{ @ @ ,& C`q=! @ @ @ 8qZ@ď1݃ @ @ KOUz^X_|Uv=2_Uz'^'C @ @ @ 82
8N^EC?O?B @ @ 8Cl% JAB[ni;,Dd@ @ @ p~J}Uz駯^z>J=frs#RƐpC
rHB @ @ p~>PA["" C{"hܘ"ܾ}aׯ; ?0
8-$ @ @ @ G+bO۷®B7"PJ#1V"F3 @ @ @`~*
ozR/}yHZ4bG;"d0
U;j5 @ @ Pq.WAb?PZP,J
%5t@ @ @ 0N`Xdr8_\~Kcm_2=BS @ @ BA^zɞyh!v8o
͛7GS+hO@ @ @ nrV"G"K
%DBS @ @ pbq_
/z2O=ԍ7}dH{キ;/IHoiK˕ @ @ @ 8v9`zDv
(Q^pqaQ鈘`* @ @ @"ǸA%G2mx%A
^J2+A @ @ ph}8_([o[>4
)>ʜ問G;tΝRէP:`V"@ @ @ pAq
a 8=J$1oQߏV@IH#F]ksAx$@ @ @ 8y%0?TAD6 _49
x1BԕC B "@ @ @ GGU}ttojp|mou?|cx kpToR%v96AV矷6mC @ @ @X8
|9^p!re
o'$:#CPA[#0$@ @ @ C/]=~J}