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Cecilia Jiménez-Sánchez, Mariló Olivares-Vicente, Celia Rodríguez-Pérez, María Herranz-López, Jesús Lozano-Sánchez, Antonio Segura-Carretero, Alberto Fernández-Gutiérrez, José Antonio Encinar, Vicente Micol
AMPK modulatory activity of olive–tree leaves phenolic compounds: Bioassay-guided isolation on adipocyte model and in silico approach
www.plosone.org
www.plosone.org
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(18)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(19)Tj
0 g
(].)Tj
3.2541 0 Td
(These)Tj
2.5682 0 Td
(findings)Tj
3.4923 0 Td
(led)Tj
1.4173 0 Td
(us)Tj
1.1055 0 Td
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1.0261 0 Td
(postulate)Tj
3.8324 0 Td
(that)Tj
1.7802 0 Td
(these)Tj
2.2563 0 Td
(compounds)Tj
4.955 0 Td
(could)Tj
2.4548 0 Td
(also)Tj
1.7688 0 Td
(have)Tj
2.0579 0 Td
(impor-)Tj
-33.715 -1.3039 Td
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(implications)Tj
5.176 0 Td
(in)Tj
1.0375 0 Td
(metabolic)Tj
4.1442 0 Td
(stress-related)Tj
5.4709 0 Td
(disorders)Tj
3.9401 0 Td
(such)Tj
2.0579 0 Td
(as)Tj
1.0148 0 Td
(obesity)Tj
3.0388 0 Td
(through)Tj
3.4469 0 Td
(AMPK-depen-)Tj
-31.1242 -1.2982 Td
(dent)Tj
2.0182 0 Td
(mechanisms.)Tj
-0.822 -1.2983 Td
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1.1111 0 Td
(this)Tj
1.6725 0 Td
(context,)Tj
3.4129 0 Td
(we)Tj
1.3266 0 Td
(have)Tj
2.0579 0 Td
(studied)Tj
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(the)Tj
1.474 0 Td
(capacity)Tj
3.4696 0 Td
(of)Tj
1.0148 0 Td
(an)Tj
1.2019 0 Td
(Olive-tree)Tj
4.2292 0 Td
(leaves)Tj
2.5625 0 Td
(extract)Tj
2.9311 0 Td
(to)Tj
1.0261 0 Td
(modulate)Tj
4.0025 0 Td
(tri-)Tj
-35.841 -1.2983 Td
(glyceride)Tj
3.821 0 Td
(accumulation)Tj
5.675 0 Td
(and)Tj
1.7347 0 Td
(AMPK)Tj
3.0274 0 Td
(activation)Tj
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(using)Tj
2.3867 0 Td
(the)Tj
1.4684 0 Td
(well-established)Tj
6.548 0 Td
(3T3-L1)Tj
3.1464 0 Td
(adipocyte)Tj
-31.9632 -1.3039 Td
(model.)Tj
2.9706 0 Td
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1.7802 0 Td
(characterization)Tj
6.6614 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(phenolic)Tj
3.685 0 Td
(extract)Tj
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(RP-HPLC-ESI-TOF/)Tj
-28.3009 -1.2982 Td
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1.8141 0 Td
(and)Tj
1.7291 0 Td
(semi-preparative)Tj
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(fractionation)Tj
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1.7008 0 Td
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(to)Tj
1.0262 0 Td
(identify)Tj
3.2938 0 Td
(putative)Tj
3.4412 0 Td
(candidates)Tj
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1.3833 0 Td
(the)Tj
-35.6879 -1.2983 Td
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(activity.)Tj
3.3448 0 Td
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0.9071 0 Td
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4.2179 0 Td
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1.7007 0 Td
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1.0262 0 Td
(obtain)Tj
2.7779 0 Td
(the)Tj
1.474 0 Td
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-34.3046 -1.3039 Td
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(variation)Tj
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(the)Tj
1.4683 0 Td
(molecular)Tj
4.2236 0 Td
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1.0148 0 Td
(the)Tj
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4.0591 0 Td
(compounds)Tj
4.955 0 Td
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1.2756 0 Td
(the)Tj
1.474 0 Td
(AMPK)Tj
3.0273 0 Td
(alpha-)Tj
-34.8715 -1.2983 Td
(2,)Tj
0.9184 0 Td
(beta)Tj
1.8822 0 Td
(and)Tj
1.7348 0 Td
(gamma)Tj
3.1917 0 Td
(subunits)Tj
3.617 0 Td
(to)Tj
1.0262 0 Td
(search)Tj
2.7609 0 Td
(for)Tj
1.3833 0 Td
(direct)Tj
2.5341 0 Td
(AMPK)Tj
3.0274 0 Td
(interaction.)Tj
4.8359 0 Td
(Finally,)Tj
3.1691 0 Td
(a)Tj
0.652 0 Td
(correlation)Tj
-30.733 -1.2983 Td
(between)Tj
3.5262 0 Td
(the)Tj
1.4684 0 Td
(most)Tj
2.2053 0 Td
(active)Tj
2.5228 0 Td
(Olive-tree)Tj
4.2293 0 Td
(leaves)Tj
2.5625 0 Td
(compounds)Tj
4.9549 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4683 0 Td
(cellular)Tj
3.1408 0 Td
(model)Tj
2.7439 0 Td
(and)Tj
1.7291 0 Td
(those)Tj
2.3358 0 Td
(bearing)Tj
-33.9248 -1.3039 Td
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(free)Tj
1.7291 0 Td
(energy)Tj
2.9083 0 Td
(values)Tj
2.6646 0 Td
(is)Tj
0.8504 0 Td
(proposed)Tj
3.9514 0 Td
(for)Tj
1.3833 0 Td
(the)Tj
1.4684 0 Td
(rational)Tj
3.3278 0 Td
(understanding)Tj
6.0718 0 Td
(of)Tj
1.0148 0 Td
(AMPK)Tj
3.0274 0 Td
(modulation)Tj
4.9039 0 Td
(by)Tj
-35.7503 -1.2982 Td
(the)Tj
1.4683 0 Td
(extract.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 518.2866 cm
BT
/F2 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
(Materials)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 483.2503 cm
BT
/F5 1 Tf
1 TL
-0.004 Tc
0 0 Td
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1.627 0 Td
(the)Tj
1.4684 0 Td
(semi-preparative)Tj
6.9505 0 Td
(fractionation)Tj
5.4141 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(Olive-tree)Tj
4.2293 0 Td
(leaves)Tj
2.5625 0 Td
(extract,)Tj
3.1578 0 Td
(all)Tj
1.1452 0 Td
(chemicals)Tj
4.1499 0 Td
(were)Tj
2.1203 0 Td
(of)Tj
-35.3081 -1.2982 Td
(analytical)Tj
4.0024 0 Td
(reagent)Tj
3.1862 0 Td
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2.4434 0 Td
(and)Tj
1.7291 0 Td
(were)Tj
2.1203 0 Td
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2.0636 0 Td
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1.0148 0 Td
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3.7588 0 Td
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4.0988 0 Td
(used)Tj
2.058 0 Td
(for)Tj
1.3889 0 Td
(the)Tj
1.4684 0 Td
(extraction)Tj
4.2576 0 Td
(was)Tj
1.7008 0 Td
(pur-)Tj
-35.2911 -1.2983 Td
(chased)Tj
2.9139 0 Td
(from)Tj
2.2054 0 Td
(Panreac)Tj
3.4185 0 Td
(\(Barcelona,)Tj
4.7509 0 Td
(Spain\).)Tj
3.0274 0 Td
(Acetic)Tj
2.7382 0 Td
(acid)Tj
1.8765 0 Td
(and)Tj
1.7292 0 Td
(acetonitrile)Tj
4.7281 0 Td
(for)Tj
1.3833 0 Td
(semi-preparative)Tj
-28.7714 -1.3039 Td
(HPLC)Tj
2.7495 0 Td
(were)Tj
2.1203 0 Td
(purchased)Tj
4.3314 0 Td
(from)Tj
2.2053 0 Td
(Fluka)Tj
2.4548 0 Td
(and)Tj
1.7291 0 Td
(Sigma-Aldrich)Tj
6.0831 0 Td
(\(Steinheim,)Tj
4.8359 0 Td
(Germany\),)Tj
4.5524 0 Td
(respectively.)Tj
-31.0618 -1.2983 Td
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2.7099 0 Td
(was)Tj
1.7007 0 Td
(purified)Tj
3.4073 0 Td
(by)Tj
1.1848 0 Td
(a)Tj
0.652 0 Td
(Milli-Q)Tj
3.2371 0 Td
(system)Tj
2.9367 0 Td
(from)Tj
2.2054 0 Td
(Millipore)Tj
3.9628 0 Td
(\(Bedford,)Tj
4.0081 0 Td
(MA,)Tj
2.0239 0 Td
(USA\).)Tj
2.6816 0 Td
(3T3-L1)Tj
3.1464 0 Td
(mouse)Tj
-33.8567 -1.2982 Td
(embryo)Tj
3.2995 0 Td
(fibroblasts)Tj
4.371 0 Td
(were)Tj
2.1203 0 Td
(purchased)Tj
4.3369 0 Td
(from)Tj
2.2054 0 Td
(the)Tj
1.4683 0 Td
(American)Tj
4.1896 0 Td
(Type)Tj
2.228 0 Td
(Culture)Tj
3.2768 0 Td
(Collection)Tj
4.354 0 Td
(\(Manassas,)Tj
-31.8498 -1.3039 Td
(VA,)Tj
1.8255 0 Td
(USA\).)Tj
2.6815 0 Td
(Dexamethasone)Tj
6.6217 0 Td
(\(DEX\),)Tj
3.0841 0 Td
(3-isobutyl-1-methylxanthine)Tj
11.673 0 Td
(\(IBMX\),)Tj
3.5886 0 Td
(insulin,)Tj
3.2145 0 Td
(penicillin)Tj
-32.6889 -1.2983 Td
(streptomycin,)Tj
5.7372 0 Td
(calf)Tj
1.6101 0 Td
(serum,)Tj
2.948 0 Td
(fetal)Tj
1.9106 0 Td
(bovine)Tj
2.9253 0 Td
(serum)Tj
2.7269 0 Td
(\(FBS\))Tj
2.4831 0 Td
(\(both)Tj
2.3981 0 Td
(being)Tj
2.4321 0 Td
(HyClone\),)Tj
4.3937 0 Td
(paraformaldehyde)Tj
-29.5651 -1.2983 Td
(solution,)Tj
3.7076 0 Td
(and)Tj
1.7292 0 Td
(Triton)Tj
2.8233 0 Td
(X-100)Tj
2.6532 0 Td
(were)Tj
2.1203 0 Td
(obtained)Tj
3.7303 0 Td
(from)Tj
2.211 0 Td
(Sigma-Aldrich)Tj
6.0775 0 Td
(\(Madrid,)Tj
3.8041 0 Td
(Spain\).)Tj
3.0273 0 Td
(Dulbecco's)Tj
-31.8838 -1.2982 Td
(modified)Tj
3.838 0 Td
(Eagle's)Tj
2.9254 0 Td
(medium)Tj
3.5999 0 Td
(\(DMEM\))Tj
3.9799 0 Td
(was)Tj
1.6894 0 Td
(purchased)Tj
4.3256 0 Td
(from)Tj
2.1997 0 Td
(Gibco)Tj
2.6306 0 Td
(\(ThermoFisher)Tj
6.2928 0 Td
(Scientific,)Tj
4.1159 0 Td
(Wal-)Tj
-35.5972 -1.304 Td
(tham,)Tj
2.5228 0 Td
(MA,)Tj
2.0239 0 Td
(USA\).)Tj
2.6816 0 Td
(Polyvinyldifluoride)Tj
7.9086 0 Td
(\(PVD\))Tj
2.8913 0 Td
(filters,)Tj
2.7042 0 Td
(0.22)Tj
/F12 1 Tf
1.8709 0 Td
[()]TJ
/F5 1 Tf
(m,)Tj
1.7688 0 Td
(were)Tj
2.126 0 Td
(obtained)Tj
3.7303 0 Td
(from)Tj
2.2054 0 Td
(Millipore)Tj
-32.4338 -1.2982 Td
(\(Bedford,)Tj
4.0081 0 Td
(MA,)Tj
2.0239 0 Td
(USA\),)Tj
2.6816 0 Td
(and)Tj
1.7291 0 Td
(Dulbecco's)Tj
4.5921 0 Td
(phosphate)Tj
4.3313 0 Td
(buffered)Tj
3.5773 0 Td
(saline)Tj
2.5002 0 Td
(\(PBS\))Tj
2.5171 0 Td
(was)Tj
1.6951 0 Td
(obtained)Tj
3.7361 0 Td
(from)Tj
-33.3919 -1.2983 Td
(Sigma-Aldrich)Tj
6.0774 0 Td
(\(St.)Tj
1.559 0 Td
(Louis,)Tj
2.6476 0 Td
(MO,)Tj
2.0863 0 Td
(USA\).)Tj
2.6815 0 Td
(The)Tj
1.7802 0 Td
(staining)Tj
3.4129 0 Td
(AdipoRed)Tj
4.2916 0 Td
(Assay)Tj
2.5171 0 Td
(Reagent)Tj
3.4356 0 Td
(was)Tj
1.6951 0 Td
(obtained)Tj
-32.1843 -1.3039 Td
(from)Tj
2.2053 0 Td
(Lonza)Tj
2.6589 0 Td
(\(Walkersville,)Tj
5.7203 0 Td
(MD)Tj
1.8538 0 Td
(USA\).)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 281.1401 cm
BT
/F0 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Preparation)Tj
5.3244 0 Td
(of)Tj
1.0441 0 Td
(the)Tj
1.5969 0 Td
(Olive-tree)Tj
4.5024 0 Td
(leaves)Tj
3.0756 0 Td
(extract)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 264.1322 cm
BT
/F5 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Olive-tree)Tj
4.2235 0 Td
(leaves)Tj
2.5625 0 Td
(\()Tj
/F10 1 Tf
[()-1()4( )7(\n)]TJ
2.3698 0 Td
[( )2()12()20()11(\r)4(\n)6( )7(\n)]TJ
/F5 1 Tf
(\))Tj
4.1442 0 Td
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2.2054 0 Td
(the)Tj
1.474 0 Td
(`Arbequina')Tj
4.9266 0 Td
(cultivar)Tj
3.2428 0 Td
(were)Tj
2.1259 0 Td
(used)Tj
2.058 0 Td
(in)Tj
1.0375 0 Td
(this)Tj
1.6724 0 Td
(study.)Tj
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-34.6561 -1.2982 Td
(were)Tj
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(air-dried)Tj
3.7587 0 Td
(in)Tj
1.0374 0 Td
(the)Tj
1.4684 0 Td
(laboratory,)Tj
4.5807 0 Td
(and)Tj
1.7292 0 Td
(sample)Tj
3.0217 0 Td
(extraction)Tj
4.2576 0 Td
(was)Tj
1.6951 0 Td
(performed)Tj
4.473 0 Td
(as)Tj
1.0148 0 Td
(described)Tj
4.0479 0 Td
(elsewhere)Tj
-33.2048 -1.3039 Td
([)Tj
0.83 0.64 0.02 0 k
(20)Tj
0 g
(].)Tj
2.0749 0 Td
(Briefly,)Tj
3.0784 0 Td
(dry)Tj
1.5704 0 Td
(leaves)Tj
2.5625 0 Td
(\(5)Tj
1.0375 0 Td
(g\))Tj
1.0261 0 Td
(were)Tj
2.1203 0 Td
(crushed)Tj
3.3845 0 Td
(and)Tj
1.7292 0 Td
(extracted)Tj
3.8834 0 Td
(via)Tj
1.3776 0 Td
(UltraTurrax)Tj
6.0095 0 Td
(T18)Tj
1.7858 0 Td
(basic)Tj
2.211 0 Td
(reagent)Tj
-33.8511 -1.2983 Td
(\(IKA,)Tj
2.4831 0 Td
(Staufen,)Tj
3.4412 0 Td
(Germany\))Tj
4.3257 0 Td
(using)Tj
2.3924 0 Td
(300)Tj
1.6441 0 Td
(mL)Tj
1.576 0 Td
(of)Tj
1.0148 0 Td
(MeOH/H)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 408.0755 223.4834 cm
BT
/F5 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(2)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 411.6472 225.1275 cm
BT
/F5 1 Tf
1 TL
-0.004 Tc
0 0 Td
(O)Tj
0.9637 0 Td
(\(80/20\).)Tj
3.3619 0 Td
(After)Tj
2.2847 0 Td
(solvent)Tj
3.0557 0 Td
(evaporation,)Tj
5.2101 0 Td
(the)Tj
-36.0394 -1.2982 Td
(extracts)Tj
3.2939 0 Td
(were)Tj
2.1203 0 Td
(reconstituted)Tj
5.4991 0 Td
(with)Tj
1.9956 0 Td
(MeOH/H)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 368.3905 210.444 cm
BT
/F5 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(2)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 371.9622 212.1448 cm
BT
/F5 1 Tf
1 TL
-0.004 Tc
0 0 Td
(O)Tj
0.9637 0 Td
(\(50/50\))Tj
3.1351 0 Td
(to)Tj
1.0262 0 Td
(achieve)Tj
3.1691 0 Td
(a)Tj
0.6576 0 Td
(concentration)Tj
5.8167 0 Td
(of)Tj
1.0148 0 Td
(50)Tj
1.1735 0 Td
(mg/mL.)Tj
-34.1515 -1.3039 Td
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2.5738 0 Td
(extraction)Tj
4.2577 0 Td
(replicates)Tj
3.9854 0 Td
(were)Tj
2.126 0 Td
(processed.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 165.9968 cm
BT
/F0 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Analytical)Tj
4.4409 0 Td
(characterization)Tj
7.1954 0 Td
(of)Tj
1.0441 0 Td
(the)Tj
1.5921 0 Td
(Olive-tree)Tj
4.5071 0 Td
(leaves)Tj
3.0709 0 Td
(extract)Tj
3.1985 0 Td
(and)Tj
1.8614 0 Td
(isolated)Tj
-26.9104 -1.1669 Td
(fractions)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 134.9858 cm
BT
/F5 1 Tf
1 TL
-0.004 Tc
0 0 Td
(The)Tj
1.7801 0 Td
(Olive-tree)Tj
4.2293 0 Td
(leaves)Tj
2.5625 0 Td
(extract)Tj
2.931 0 Td
(was)Tj
1.7007 0 Td
(analytically)Tj
4.7055 0 Td
(characterized)Tj
5.5616 0 Td
(by)Tj
1.1792 0 Td
(RP-HPLC-ESI-TOF/MS,)Tj
10.1763 0 Td
(per-)Tj
-34.8262 -1.2982 Td
(formed)Tj
3.1577 0 Td
(in)Tj
1.0318 0 Td
(an)Tj
1.2019 0 Td
(Agilent)Tj
3.1578 0 Td
(1200-HPLC)Tj
5.0003 0 Td
(system)Tj
2.9366 0 Td
(\(Agilent)Tj
3.4923 0 Td
(Technologies,)Tj
5.76 0 Td
(Waldbronn,)Tj
5.0966 0 Td
(Germany\))Tj
4.3313 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
-36.1811 -1.2983 Td
(Series)Tj
2.5398 0 Td
(Rapid)Tj
2.5908 0 Td
(Resolution)Tj
4.5241 0 Td
(equipped)Tj
3.9345 0 Td
(with)Tj
1.9955 0 Td
(a)Tj
0.652 0 Td
(vacuum)Tj
3.4072 0 Td
(degasser,)Tj
3.8154 0 Td
(autosampler,)Tj
5.3858 0 Td
(a)Tj
0.652 0 Td
(binary)Tj
2.8006 0 Td
(pump,)Tj
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