ライフサイエンスコーパス: SELEX

1 SELEX analysis identified GC-rich RNA sequences as a com

2 SELEX assays and footprinting data indicate that DEAF-1

3 SELEX coupled with SPR is expected to speed up the selec

4 SELEX directed against the RNA-binding face of the STNV

5 SELEX experiments with human Fox-1 revealed highly selec

6 SELEX of the combined H4a and H4b region in satC generat

7 SELEX selections for repeats 5 and 2 enriched for oligon

8 SELEX with a N30 RNA pool yielded an aptamer (B6) that b

9 SELEX, however, is an iterative process requiring multip

10 SELEX-generated RNA aptamers are proving to be highly ef

11 A SELEX (systematic evolution of ligands by exponential en

12 A SELEX procedure using paired KH-domains defined the pref

13 eviously published KLF motif identified by a SELEX experiment, but the new motif is consistent with m

14 Exonization was promoted by a SELEX-predicted heptamer in Alu consensus sequence 222-2

15 sequence-randomized region was employed in a SELEX-type procedure to identify DNAs that bound strongl

16 We tested this hypothesis using a SELEX experimental design and found that non-specific RN

17 AEGIS-SELEX delivered an AEGIS aptamer (ZAP-2012) built from s

18 ower and utility of SELEX and offer an AEGIS-SELEX that could possibly generate receptors, ligands, a

19 The success of AEGIS-SELEX relies on various innovations, including (i) the a

20 This AEGIS-SELEX was designed to create AEGIS oligonucleotides that

21 After SELEX, the aptamers were identified by the alignment ana

22 algorithm, originally implemented to analyze SELEX data; extends the applicability of AptaMotif to HT

23 us on the novel applications of aptamers and SELEX, as well as opportunities to develop molecular too

24 led to diverse aptamers, both biological and SELEX-derived, using simple design rules.

25 Analyzing structural data and SELEX-seq experimental results, we deduced the DNA seque

26 ding specificity was analyzed using EMSA and SELEX.

27 s (uPBMs), genomic context PBMs (gcPBMs) and SELEX-seq data, we demonstrate that incorporating DNA sh

28 ing sites obtained from the B1H, DNase I and SELEX methodologies are presented.

29 ule using in vitro selection (referred to as SELEX).

30 A PCR-assisted site selection assay (SELEX) of recombinant OsWRKY47 protein showed that the p

31 ed on the integration of magnetic bead-based SELEX process with microfluidics technology.

32 ress this challenge, we have used cell-based SELEX (Systematic Evolution of Ligands by Exponential En

33 The cell-based SELEX is simple, fast, and robust.

34 he aptamers were selected using a cell-based SELEX strategy in our laboratory for cancer cells that,

35 mer sequence was selected using a cell-based SELEX strategy in our laboratory for CCRF-CEM acute leuk

36 dily conjugated to magnetic beads, MMS-based SELEX provides a general platform for rapid generation o

37 A surface plasmon resonance (SPR)-based SELEX approach has been used to raise RNA aptamers again

38 re in vitro selected using a new single-bead SELEX approach, which was rapid and consumed only ca. 45

39 Before SELEX, silane chemistry was used to prepare epoxide-func

40 BLI-SELEX is a one-step technique for rapidly generating apt

41 etry based in-vitro selection technique (BLI-SELEX) for fishing out specific aptamers against E. coli

42 on of an optimal binding sequence for BEN by SELEX (systematic evolution of ligands by exponential en

43 to unnatural-base DNA aptamers generated by SELEX using genetic alphabet expansion, without reducing

44 The RNA sequences identified by SELEX are structured and contain a five-nucleotide conse

45 target 17beta-estradiol (E2) was isolated by SELEX with dissociation constant of 50 nM and tethered t

46 r only a subset of the sequences obtained by SELEX leads to a much more accurate model.

47 the preferred DNA binding sequence of Opa by SELEX and shown that it is necessary and sufficient to a

48 n designed in the past either manually or by SELEX (Systematic Evolution of Ligands by Exponential En

49 o-recognition elements which are produced by SELEX (systematic evolution of ligands by exponential en

50 d neurotransmitters for aptamer selection by SELEX.

51 Using the Capture-SELEX procedure, we here describe the selection of an ap

52 rounds using capillary electrophoresis (CE)-SELEX.

53 the first report of aptamers isolated by CE-SELEX with higher affinity than those obtained for the s

54 ion of ligands by exponential enrichment (CE-SELEX) and had a dissociation constant (K(d)) of 112 nM.

55 ion of ligands by exponential enrichment (CE-SELEX) has previously been used to select aptamers for l

56 ion of ligands by exponential enrichment (CE-SELEX) is a powerful technique for isolating aptamers fo

57 onucleotide motifs are rarely reported in CE-SELEX studies.

58 sults also provided insight into why many CE-SELEX selections obtain pools with reduced affinities af

59 One of the unique characteristics of CE-SELEX is the relatively high heterogeneity of the ssDNA

60 ucleotide pool through multiple rounds of CE-SELEX selection against the target recombinant human vas

61 For the first time, we have performed CE-SELEX selection for a small-molecule target, N-methyl me

62 Capillary electrophoresis-SELEX (CE-SELEX) was used to select ssDNA aptamers with affinity f

63 was observed, supporting the premise that CE-SELEX selects a uniquely heterogeneous pool of high affi

64 Using human embryonic stem cell SELEX-Seq data, MPBind achieved high prediction accuracy

65 steria spp. were selected using a whole-cell SELEX (Systematic Evolution of Ligands by EXponential en

66 A method known as cell-SELEX (systematic evolution of ligands by exponential en

67 t ovarian cancer previously obtained by cell-SELEX (SELEX = systematic evolution of ligands by expone

68 is challenge, aptamers were selected by cell-SELEX (Systematic Evolution of Ligands by EXponential en

69 DNA aptamers generated by cell-SELEX against bacterial cells have gained increased inte

70 ecognized by aptamer M17A2 generated by cell-SELEX against MCF-7R cells.

71 identification of aptamers obtained by cell-SELEX can serve as a means to identify promising biomark

72 DNA aptamers generated by cell-SELEX offer an attractive alternative to antibodies, but

73 Here we screened the aptamer CH6 by cell-SELEX, specifically targeting both rat and human osteobl

74 selected a DNA aptamer against GCGR by cell-SELEX, which can specifically bind membrane protein of C

75 By applying newly developed cell-SELEX (cell-based systematic evolution of ligands by exp

76 We applied a newly developed cell-SELEX (Systematic Evolution of Ligands by EXponential en

77 n of Ligands by Exponential Enrichment (Cell-SELEX) and development of sandwich type aptamer-based co

78 n of Ligands by Exponential Enrichment (Cell-SELEX) to identify glioblastoma TIC-specific nucleic aci

79 seful to study and improve experimental cell-SELEX designs to increase selection efficiency.

80 report a DNA aptamer probe evolved from cell-SELEX that can recognize thrombospondin-1 protein in hum

81 Thus, with the aptamer obtained from cell-SELEX, real-time modification of live-cell membrane prot

82 DNA aptamers (generated with a modified cell-SELEX procedure to display low-nanomolar affinity for th

83 ch served as target in eleven rounds of cell-SELEX with multiple subtractive counter-selections again

84 After six rounds of cell-SELEX, high-throughput sequencing and bioinformatics ana

85 ells using a combined approach based on cell-SELEX, state-of-the-art applications of quantitative rea

86 This protocol, cell-SELEX (systematic evolution of ligands by exponential en

87 new results (compared with our reported cell-SELEX methodology) in addition to the generation of apta

88 ed the procedure STACS (Specific TArget Cell-SELEX).

89 ucement); and the second result is that cell-SELEX can be used for adhesive cells and thus open the d

90 The cell-SELEX uses whole live cells as targets to select aptamer

91 tact vaccinia virus were selected using cell-SELEX technique and integrated into impedimetric sensors

92 In this study, using Cell-SELEX with positive selection for TICs and negative sele

93 almonella enteritidis were selected via Cell-SELEX technique.

94 efficient method of affinity chromatography-SELEX followed by a quantitative binding (QuMFRA) assay

95 ned efficiently with affinity chromatography-SELEX, but those sequences alone provide a weight matrix

96 A classic SELEX process was designed employing magnetic beads for

97 High-Throughput (HT) SELEX combines SELEX (Systematic Evolution of Ligands by EXponential En

98 In this study, a conventional SELEX approach was applied against the kinase domain of

99 st high-affinity aptamers as in conventional SELEX.

100 In contrast to the conventional SELEX methodology, selection and mutation of aptamer seq

101 DNA aptamers selected using the conventional SELEX protocol, and their application in an ELISA assay

102 (Kd 14nM), screened by new in-situ developed SELEX method using phenylboronic acid on microtitre plat

103 A doped SELEX was performed on a known MBNL1-binding site.

104 During SELEX, the ligand evolution was assured by a differentia

105 on of ligands by exponential enrichment (egg-SELEX) and identified a panel of ssDNA aptamers specific

106 Capillary electrophoresis-SELEX (CE-SELEX) was used to select ssDNA aptamers with

107 lution of Ligands by EXponential enrichment (SELEX) (in vitro).

108 lution of ligands by exponential enrichment (SELEX) analysis, the enormous datasets generated in the

109 lution of ligands by exponential enrichment (SELEX) and NMR spectroscopy to demonstrate that the majo

110 lution of ligands by exponential enrichment (SELEX) approach.

111 lution of ligands by exponential enrichment (SELEX) approaches, the ability of NECEEM to select aptam

112 lution of ligands by exponential enrichment (SELEX) due to its small size and scarcity of reactive gr

113 lution of ligands by exponential enrichment (SELEX) exhibited dissociation constants in the nanomolar

114 lution of ligands by exponential enrichment (SELEX) experiment.

115 lution of ligands by exponential enrichment (SELEX) in conjunction with high throughput sequencing wa

116 lution of ligands by exponential enrichment (SELEX) in vitro, which allows for sensitive detection of

117 lution of ligands by exponential enrichment (SELEX) is a screening technique that involves the progre

118 n of ligands through exponential enrichment (SELEX) is a well-established method for generating nucle

119 lution of Ligands by Exponential Enrichment (SELEX) method, which can generate a nucleic acid-based p

120 lution of ligands by exponential enrichment (SELEX) method.

121 lution of Ligands by Exponential Enrichment (SELEX) methodology and the description of the first apta

122 lution of Ligands by EXponential Enrichment (SELEX) offers an iterative process to discover these apt

123 lution of ligands by exponential enrichment (SELEX) or random binding site selection (RBSS).

124 lution of ligands by exponential enrichment (SELEX) procedure, we have identified two consensus seque

125 lution of ligands by exponential enrichment (SELEX) process enables the isolation of aptamers from ra

126 lution of ligands by exponential enrichment (SELEX) process is used for the isolation of specific, hi

127 lution of ligands by exponential enrichment (SELEX) process to discover slow off-rate modified aptame

128 lution of Ligands by Exponential Enrichment (SELEX) protocol capable of selecting xeno-nucleic acid (

129 lution of ligands by exponential enrichment (SELEX) protocol identified a single, efficiently cleaved

130 lution of Ligands by EXponential Enrichment (SELEX) represents a state-of-the-art technology to isola

131 lution of Ligands by EXponential enrichment (SELEX) rounds display poor binding activity.

132 lution of ligands by exponential enrichment (SELEX) technique is a powerful and effective aptamer-sel

133 lution of ligands by exponential enrichment (SELEX) technique.

134 lution of ligands by exponential enrichment (SELEX) to identify the preferred binding sequence of ETR

135 lution of ligands by exponential enrichment (SELEX) to isolate RNA aptamers against aminoglycoside an

136 lution of ligands by exponential enrichment (SELEX) to isolate RNA aptamers that bind the Caenorhabdi

137 uation of ligands by exponential enrichment (SELEX) to systematically identify additional DNA sequenc

138 lution of ligands by exponential enrichment (SELEX) using nitrocellulose membranes.

139 lution of ligands by exponential enrichment (SELEX) was a labor-intensive and time-consuming process,

140 lution of ligands by exponential enrichment (SELEX) was used to identify RNA sequences that bind Mbl

141 lution of ligands by exponential enrichment (SELEX)) are often labor-intensive and time-consuming.

142 lution of ligands by exponential enrichment (SELEX), we found a single 58-nt aptamer sequence that as

143 lution of ligands by exponential enrichment (SELEX), we have selected a group of RNA aptamers against

144 lution of Ligands by EXponential Enrichment (SELEX), we identified aptamers against DUX4 with specifi

145 lution of ligands by exponential enrichment (SELEX), we identified DNA sequences that bound to the HT

146 lution of ligands by exponential enrichment (SELEX), we identify DNA aptamers that bind specifically

147 lution of ligands by exponential enrichment (SELEX).

148 lution of ligands by exponential enrichment (SELEX).

149 lution of ligands by exponential enrichment (SELEX).

150 lution of ligands by exponential enrichment (SELEX).

151 lution of Ligands by EXponential enrichment (SELEX).

152 lution of ligands by exponential enrichment (SELEX).

153 ution of ligands via exponential enrichment (SELEX).

154 lution of ligands by exponential enrichment (SELEX).

155 olution of ligand by exponential enrichment (SELEX).

156 lution of ligands by exponential enrichment (SELEX).

157 ion of splicing and polyadenylation by ESRP, SELEX-Seq analysis was performed, coupling traditional S

158 mers derived from combinatorial experiments (SELEX or phage display).

159 itro RNA-binding site selection experiments (SELEX) identified distinct binding motif specificities f

160 of Ligands by Exponential Enrichment (FluMag-SELEX) method to isolate a urea specific DNA aptamer wit

161 o fIXa, which was previously determined from SELEX measurements.

162 ith the facile recovery of these motifs from SELEX experiments.

163 regulatory motifs, substitute for functional SELEX in most cases, and provide insights about splicing

164 We have now carried out a refined functional SELEX screen for motifs that can act as ESEs in response

165 nstrate the feasibility of employing genomic SELEX to identify vertebrate transcription factor bindin

166 Evolution of these single-hairpin SELEX winners in plants resulted in satC that can accumu

167 However, SELEX is a lengthy, labor-intensive, iterative process r

168 High-Throughput (HT) SELEX combines SELEX (Systematic Evolution of Ligands by

169 We applied these methods to an HT-SELEX experiment developing aptamers against Interleukin

170 eloped novel in-silico methods to analyze HT-SELEX data and utilized them to study the emergence of p

171 we developed a novel framework to analyze HT-SELEX data.

172 to compare output results from different HT-SELEX cycles.

173 parison of solution PCR- and ddPCR-driven HT-SELEX demonstrated that PCR method affected not only the

174 the emergence of polymerase errors during HT-SELEX.

175 to identify target-specific aptamers from HT-SELEX data and secondary structure information.

176 presence of motif-free sequences in late HT-SELEX rounds and their enrichment in weak binders allows

177 ms for estimating binding motifs based on HT-SELEX data.

178 published motifs estimated using the same HT-SELEX data, we demonstrate that BEESEM provides signific

179 oinformatics analysis coupled with SELEX (HT-SELEX) to thoroughly investigate the effects of initial

180 roarrays (PBM) and high-throughput SELEX (HT-SELEX), have enabled rapid measurements of the specifici

181 coupled with high-throughput sequencing (HT-SELEX), creates billions of random sequences capable of

182 extends the applicability of AptaMotif to HT-SELEX data and introduces new functionalities, as the po

183 In this study, we use HT-SELEX derived populations to study the landscape of RNAs

184 The model is validated using HT-SELEX and generated datasets, and by comparing to some e

185 of 239 and 56 TFs extracted from in vitro HT-SELEX binding assays and in vivo ChIP-seq data, respecti

186 proach to analyze the results of in vitro HT-SELEX experiments for TF-DNA binding.

187 icities using high-throughput RNA-SELEX (HTR-SELEX).

188 focusing in spiral microfluidic channels, I-SELEX enables stringent partitioning of cells (efficienc

189 Here we use a novel strategy (I-SELEX) to discover high affinity aptamers that selective

190 These findings validate I-SELEX as a broadly applicable aptamer discovery platform

191 This perspective covers recent advances in SELEX methodology for improving efficiency of the SELEX

192 This review summarizes recent advances in SELEX that improve the affinity and specificity of DNAzy

193 et concentration, on selection efficiency in SELEX and identify strategies to control these uncertain

194 For instance, in SELEX experiments, each urn could represent a random RNA

195 f our approach to identify binding motifs in SELEX data.

196 entification of sequence-structure motifs in SELEX-derived aptamers.

197 eic acid libraries improves success rates in SELEX experiments and facilitates the identification of

198 Target immobilization plays a key role in SELEX and other ligand enrichment methods, particularly

199 stationary phase to serve as the targets in SELEX.

200 e a variety of RNA binding assays, including SELEX, to characterize the interaction in vitro and a mo

201 (ddPCR) has been recently incorporated into SELEX selection protocols to putatively reduce the propa

202 i-Mb aptamer was generated by five iterative SELEX (Systematic evolution of ligands by exponential en

203 We present here an alternative M-SELEX method, which employs a disposable microfluidic ch

204 Our microfluidic SELEX (M-SELEX) method exploits a number of unique phenomena that

205 t studies suggest that microfluidic SELEX (M-SELEX) technology can accelerate aptamer isolation by en

206 model to demonstrate the efficiency of the M-SELEX process, we describe here the isolation of DNA apt

207 on of ligands by exponential enrichment (MAI-SELEX), a technique designed for the efficient selection

208 Using MAI-SELEX, we have isolated two groups of 2'-fluoro-modified

209 In this marriage, SELEX adds DNA specificity determination to the YSD plat

210 tspot, we used an in vitro selection method (SELEX) that revealed an 18-bp consensus sequence for Atf

211 isting of a magnetic bead-based microfluidic SELEX chip and a competitive assay chip to automate the

212 Our microfluidic SELEX (M-SELEX) method exploits a number of unique pheno

213 Recent studies suggest that microfluidic SELEX (M-SELEX) technology can accelerate aptamer isolat

214 synthesized DNA oligonucleotides as in most SELEX studies, we utilized zebrafish genomic DNA to isol

215 the assignment of motifs to 200 TFs with no SELEX-derived motifs, roughly a 50% increase compared to

216 Mapped AtTopoIIA sites but not SELEX sites were strongly associated with T-DNA integrat

217 The advent of SELEX (systematic evolution of ligands by exponential en

218 NMR analysis of SELEX and gC sequences revealed that sequences able to b

219 Our experimental results and analysis of SELEX publications spanning 13 years implicate the alkal

220 At the same time, the combination of SELEX with novel sequencing technologies is beginning to

221 Combination of SELEX-seq and genome-wide DNA binding data allows differ

222 chieves the full microfluidic integration of SELEX, thereby enabling highly efficient isolation of ap

223 peline to Predict the BIND: ing potential of SELEX-derived aptamers.

224 candidates were isolated in three rounds of SELEX within a total process time of approximately 10 ho

225 After five rounds of SELEX, ETR-3 selected UG-rich sequences, in particular U

226 After five rounds of SELEX, MBNL1 selected pyrimidine-rich RNAs containing YG

227 Through four rounds of SELEX, we identified aptamers binding to Cry j 2.

228 ion of aptamers in the first three rounds of SELEX, while SELEX with conventional PCR failed in a num

229 ep toward expanding the power and utility of SELEX and offer an AEGIS-SELEX that could possibly gener

230 We performed ADAPT, a variant of SELEX, on exosomes secreted by VCaP prostate cancer cell

231 A-binding domains using a refined version of SELEX-seq.

232 Like other SELEX methods, repeated cycles (typically 5-15) of selec

233 onuclease single-strand recovery step in our SELEX to direct aptamers to the surface of erythrocytes

234 s is needed to understand effects on overall SELEX performance.

235 the enriched sequences, but also the overall SELEX efficiency and aptamer efficacy.

236 Here we performed parallel SELEX experiments to compare the impact of two different

237 an experimental and computational platform, SELEX-seq, that can be used to determine the relative af

238 Post-SELEX aptamer engineering can improve aptamer performanc

239 Post-SELEX optimization of one Bn-dU and one Nap-dU SOMAmer l

240 alized for the efficient and systematic post-SELEX development of aptamers for down-stream applicatio

241 containing sequences present early in the R1 SELEX process to identify novel anti-p65 RNA aptamers, t

242 Adding to this uncertainty, repeating SELEX under identical conditions may lead to variable ou

243 e interactions, we have developed an RNA-RNA SELEX approach for mapping the sequences involved in int

244 Using RNA SELEX and bioinformatics, we identified multiple regions

245 heir specificities using high-throughput RNA-SELEX (HTR-SELEX).

246 random library using the in vitro screening SELEX approach.

247 ness in plants by in vivo genetic selection (SELEX) resulted in winning sequences that contain an H4a

248 of GTF3 to random oligonucleotide selection (SELEX) to assess their DNA binding potentials.

249 iline-based quencher via in vitro selection (SELEX).

250 an cancer previously obtained by cell-SELEX (SELEX = systematic evolution of ligands by exponential e

251 of 542 human TFs with methylation-sensitive SELEX (systematic evolution of ligands by exponential en

252 tro selection combined with deep sequencing (SELEX-seq).

253 followed by high-throughput DNA sequencing (SELEX-seq) on several floral MADS domain protein homo- a

254 igands by exponential enrichment sequencing (SELEX-seq), chromatin immunoprecipitation sequencing (Ch

255 s selected against cell lines using standard SELEX.

256 ning the library using a structure-switching SELEX approach, a high affinity SA aptamer was identifie

257 y an in vitro selection process, also termed SELEX (Systematic Evolution of Ligands by EXponential en

258 terial system is, however, more limited than SELEX, and some eukaryotic factors may not express or fo

259 ressed on the surface of yeast, we show that SELEX can yield binding specificity motifs and identify

260 is is, to our knowledge, the first time that SELEX is applied to a vertebrate genome.

261 The SELEX procedure, coupled with high-throughput sequencing

262 The SELEX rounds were toggled against four pairs of aminogly

263 The mapped AtTopoIIA cleavage sites and the SELEX sites differed in their genomic distribution and a

264 nity were isolated from a RNA library by the SELEX (Systematic Evolution of Ligands by EXponential en

265 oside-aptamer recognition highlighted by the SELEX results.

266 In vivo, however, the SELEX sites improved polyadenylation in proviral clones

267 By immobilizing the SELEX library instead of SA and screening the library us

268 ides and selecting for slow off-rates in the SELEX procedure, we have evolved a special class of apta

269 This putative CsrA binding site matched the SELEX-derived binding site consensus sequence in 8 out o

270 methodology for improving efficiency of the SELEX procedure and enhancing affinity and specificity o

271 RNase footprinting of one of the SELEX RNA sequences with Mbl showed that Mbl binds both

272 Using the SELEX-identified motifs to search the human genome, we i

273 This SELEX (systematic evolution of ligands by exponential en

274 Consistent with this, SELEX-binding sites for the SR proteins ASF/SF2, 9G8, an

275 inding microarrays (PBM) and high-throughput SELEX (HT-SELEX), have enabled rapid measurements of the

276 s have been identified using high-throughput SELEX sequencing.

277 pensive, facile protein-matrix generation to SELEX.

278 a feature-based generalized linear model to SELEX probe counts.

279 s, encoded by the binding affinities, toward SELEX targets.

280 analysis was performed, coupling traditional SELEX with high-throughput sequencing.

281 h varying genome compositions and for tuning SELEX pools to optimize the chance of finding specific f

282 sponding yeast one-hybrid system and, unlike SELEX, it does not require purification of the TF(s).

283 Here the authors use SELEX to generate a modified DNA aptamer which specifica

284 Here, we use SELEX, RNA structure probing, and RNA footprinting to sh

285 We used SELEX (systematic evolution of ligands by exponential en

286 ral genome involved in this process, we used SELEX (systematic evolution of ligands by exponential en

287 recombinant murine PrP (rPrP(90-231)) using SELEX methodology.

288 Aptamers are selected using SELEX, Systematic Evolution of Ligands by EXponential en

289 synthesis of modified aptamer libraries via SELEX.

290 terize its tripartite consensus sequence via SELEX (systematic evolution of ligands by exponential en

291 AFF-R with nanomolar affinity using in vitro SELEX technology.

292 we characterized this role using an in vivo SELEX approach.

293 C) was previously identified through in vivo SELEX.

294 This is the first study in which SELEX targeted bacterial cells at different growth phase

295 rs in the first three rounds of SELEX, while SELEX with conventional PCR failed in a number of attemp

296 ogy and bioinformatics analysis coupled with SELEX (HT-SELEX) to thoroughly investigate the effects o

297 SPR coupled with SELEX from the first to the last round allowed identifyi

298 X-SELEX is initiated by the synthesis of diverse repertoir

299 enrichment by exponential amplification' (X-SELEX).

300 This approach, which we term YSD-SELEX, represents a simple and rapid first principles ap