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1                                              SELEX analysis identified GC-rich RNA sequences as a com
2                                              SELEX assays and footprinting data indicate that DEAF-1
3                                              SELEX assays identified consensus binding sites that per
4                                              SELEX coupled with SPR is expected to speed up the selec
5                                              SELEX directed against the RNA-binding face of the STNV
6                                              SELEX experiments with human Fox-1 revealed highly selec
7                                              SELEX of the combined H4a and H4b region in satC generat
8                                              SELEX selections for repeats 5 and 2 enriched for oligon
9                                              SELEX was used to identify DNA sequences favorable for g
10                                              SELEX with a N30 RNA pool yielded an aptamer (B6) that b
11                                              SELEX, however, is an iterative process requiring multip
12                                              SELEX-generated RNA aptamers are proving to be highly ef
13                                            A SELEX (systematic evolution of ligands by exponential en
14                                            A SELEX procedure using paired KH-domains defined the pref
15 eviously published KLF motif identified by a SELEX experiment, but the new motif is consistent with m
16 ed IRP6, was cloned from C. diphtheriae by a SELEX-like procedure.
17                Exonization was promoted by a SELEX-predicted heptamer in Alu consensus sequence 222-2
18 sequence-randomized region was employed in a SELEX-type procedure to identify DNAs that bound strongl
19 d the first case to report the presence of a SELEX-derived RNA aptamer in living organisms.
20 howed that g5p binds with high affinity to a SELEX-selected G-rich 58-mer DNA oligomer, I-3, that for
21                                      Using a SELEX (systematic evolution of ligands by exponential en
22            We tested this hypothesis using a SELEX experimental design and found that non-specific RN
23                                        AEGIS-SELEX delivered an AEGIS aptamer (ZAP-2012) built from s
24 ower and utility of SELEX and offer an AEGIS-SELEX that could possibly generate receptors, ligands, a
25                         The success of AEGIS-SELEX relies on various innovations, including (i) the a
26                                   This AEGIS-SELEX was designed to create AEGIS oligonucleotides that
27                                        After SELEX, the aptamers were identified by the alignment ana
28 algorithm, originally implemented to analyze SELEX data; extends the applicability of AptaMotif to HT
29 led to diverse aptamers, both biological and SELEX-derived, using simple design rules.
30 ding specificity was analyzed using EMSA and SELEX.
31 s (uPBMs), genomic context PBMs (gcPBMs) and SELEX-seq data, we demonstrate that incorporating DNA sh
32 ing sites obtained from the B1H, DNase I and SELEX methodologies are presented.
33 ule using in vitro selection (referred to as SELEX).
34         A PCR-assisted site selection assay (SELEX) of recombinant OsWRKY47 protein showed that the p
35 acement sequences, only a few of the 10-base SELEX (systematic evolution of ligands by exponential en
36 ed on the integration of magnetic bead-based SELEX process with microfluidics technology.
37 ress this challenge, we have used cell-based SELEX (Systematic Evolution of Ligands by Exponential En
38                               The cell-based SELEX is simple, fast, and robust.
39 he aptamers were selected using a cell-based SELEX strategy in our laboratory for cancer cells that,
40 mer sequence was selected using a cell-based SELEX strategy in our laboratory for CCRF-CEM acute leuk
41 dily conjugated to magnetic beads, MMS-based SELEX provides a general platform for rapid generation o
42      A surface plasmon resonance (SPR)-based SELEX approach has been used to raise RNA aptamers again
43 re in vitro selected using a new single-bead SELEX approach, which was rapid and consumed only ca. 45
44                                       Before SELEX, silane chemistry was used to prepare epoxide-func
45 on of an optimal binding sequence for BEN by SELEX (systematic evolution of ligands by exponential en
46                      RNA aptamers derived by SELEX (systematic evolution of ligands by exponential en
47  to unnatural-base DNA aptamers generated by SELEX using genetic alphabet expansion, without reducing
48              The RNA sequences identified by SELEX are structured and contain a five-nucleotide conse
49 target 17beta-estradiol (E2) was isolated by SELEX with dissociation constant of 50 nM and tethered t
50 r only a subset of the sequences obtained by SELEX leads to a much more accurate model.
51 the preferred DNA binding sequence of Opa by SELEX and shown that it is necessary and sufficient to a
52 n designed in the past either manually or by SELEX (Systematic Evolution of Ligands by Exponential En
53 o-recognition elements which are produced by SELEX (systematic evolution of ligands by exponential en
54 d neurotransmitters for aptamer selection by SELEX.
55                            Using the Capture-SELEX procedure, we here describe the selection of an ap
56  rounds using capillary electrophoresis (CE)-SELEX.
57  the first report of aptamers isolated by CE-SELEX with higher affinity than those obtained for the s
58 ion of ligands by exponential enrichment (CE-SELEX) and had a dissociation constant (K(d)) of 112 nM.
59 ion of ligands by exponential enrichment (CE-SELEX) has previously been used to select aptamers for l
60 ion of ligands by exponential enrichment (CE-SELEX) is a powerful technique for isolating aptamers fo
61 onucleotide motifs are rarely reported in CE-SELEX studies.
62 sults also provided insight into why many CE-SELEX selections obtain pools with reduced affinities af
63      One of the unique characteristics of CE-SELEX is the relatively high heterogeneity of the ssDNA
64 ucleotide pool through multiple rounds of CE-SELEX selection against the target recombinant human vas
65     For the first time, we have performed CE-SELEX selection for a small-molecule target, N-methyl me
66          Capillary electrophoresis-SELEX (CE-SELEX) was used to select ssDNA aptamers with affinity f
67 was observed, supporting the premise that CE-SELEX selects a uniquely heterogeneous pool of high affi
68              Using human embryonic stem cell SELEX-Seq data, MPBind achieved high prediction accuracy
69 steria spp. were selected using a whole-cell SELEX (Systematic Evolution of Ligands by EXponential en
70    The human embryonic stem cells whole-cell SELEX-Seq data are available at http://www.morgridge.net
71                       A method known as cell-SELEX (systematic evolution of ligands by exponential en
72 t ovarian cancer previously obtained by cell-SELEX (SELEX = systematic evolution of ligands by expone
73 is challenge, aptamers were selected by cell-SELEX (Systematic Evolution of Ligands by EXponential en
74 ecognized by aptamer M17A2 generated by cell-SELEX against MCF-7R cells.
75  identification of aptamers obtained by cell-SELEX can serve as a means to identify promising biomark
76               DNA aptamers generated by cell-SELEX offer an attractive alternative to antibodies, but
77     Here we screened the aptamer CH6 by cell-SELEX, specifically targeting both rat and human osteobl
78  selected a DNA aptamer against GCGR by cell-SELEX, which can specifically bind membrane protein of C
79             By applying newly developed cell-SELEX (cell-based systematic evolution of ligands by exp
80            We applied a newly developed cell-SELEX (Systematic Evolution of Ligands by EXponential en
81 n of Ligands by Exponential Enrichment (Cell-SELEX) and development of sandwich type aptamer-based co
82 n of Ligands by Exponential Enrichment (Cell-SELEX) to identify glioblastoma TIC-specific nucleic aci
83 report a DNA aptamer probe evolved from cell-SELEX that can recognize thrombospondin-1 protein in hum
84    Thus, with the aptamer obtained from cell-SELEX, real-time modification of live-cell membrane prot
85                     After six rounds of cell-SELEX, high-throughput sequencing and bioinformatics ana
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          High-Throughput (HT) SELEX combines SELEX (Systematic Evolution of Ligands by EXponential En
97              In contrast to the conventional SELEX methodology, selection and mutation of aptamer seq
98 DNA aptamers selected using the conventional SELEX protocol, and their application in an ELISA assay
99 Kd 14nM), screened by new in-situ developed SELEX method using phenylboronic acid on microtitre plat
100                                      A doped SELEX was performed on a known MBNL1-binding site.
101                                       During SELEX, the ligand evolution was assured by a differentia
102 ces from random RNA sequence libraries (i.e. SELEX) we find that tight binding to PP7 coat protein is
103 on of ligands by exponential enrichment (egg-SELEX) and identified a panel of ssDNA aptamers specific
104                    Capillary electrophoresis-SELEX (CE-SELEX) was used to select ssDNA aptamers with
105 lution of Ligands by EXponential enrichment (SELEX) (in vitro).
106 lution of ligands by exponential enrichment (SELEX) analysis, the enormous datasets generated in the
107 lution of ligands by exponential enrichment (SELEX) approach.
108 lution of ligands by exponential enrichment (SELEX) approaches, the ability of NECEEM to select aptam
109 lution of ligands by exponential enrichment (SELEX) exhibited dissociation constants in the nanomolar
110 lution of ligands by exponential enrichment (SELEX) experiment.
111 lution of ligands by exponential enrichment (SELEX) in conjunction with high throughput sequencing wa
112 lution of ligands by exponential enrichment (SELEX) is a screening technique that involves the progre
113 n of ligands through exponential enrichment (SELEX) is a well-established method for generating nucle
114 lution of Ligands by Exponential Enrichment (SELEX) method, which can generate a nucleic acid-based p
115 lution of ligands by exponential enrichment (SELEX) method.
116 lution of Ligands by EXponential Enrichment (SELEX) offers an iterative process to discover these apt
117 lution of ligands by exponential enrichment (SELEX) or random binding site selection (RBSS).
118 lution of ligands by exponential enrichment (SELEX) procedure, we have identified two consensus seque
119 lution of ligands by exponential enrichment (SELEX) process is used for the isolation of specific, hi
120 lution of ligands by exponential enrichment (SELEX) process to discover slow off-rate modified aptame
121 lution of ligands by exponential enrichment (SELEX) process.
122 lution of Ligands by Exponential Enrichment (SELEX) protocol capable of selecting xeno-nucleic acid (
123 lution of ligands by exponential enrichment (SELEX) protocol identified a single, efficiently cleaved
124 lution of Ligands by EXponential Enrichment (SELEX) represents a state-of-the-art technology to isola
125 lution of Ligands by EXponential enrichment (SELEX) rounds display poor binding activity.
126 lution of ligands by exponential enrichment (SELEX) technique is a powerful and effective aptamer-sel
127 lution of ligands by exponential enrichment (SELEX) technique.
128 lution of ligands by exponential enrichment (SELEX) to identify the preferred binding sequence of ETR
129 lution of ligands by exponential enrichment (SELEX) to identify the sequence specificity of the poten
130 lution of ligands by exponential enrichment (SELEX) to isolate RNA aptamers against aminoglycoside an
131 lution of ligands by exponential enrichment (SELEX) to isolate RNA aptamers that bind the Caenorhabdi
132 uation of ligands by exponential enrichment (SELEX) to systematically identify additional DNA sequenc
133 lution of ligands by exponential enrichment (SELEX) using nitrocellulose membranes.
134 lution of ligands by exponential enrichment (SELEX) was used to identify RNA sequences that bind Mbl
135 lution of ligands by exponential enrichment (SELEX)) are often labor-intensive and time-consuming.
136 lution of ligands by exponential enrichment (SELEX), we found a single 58-nt aptamer sequence that as
137 lution of ligands by exponential enrichment (SELEX), we have selected a group of RNA aptamers against
138 ution of ligands via exponential enrichment (SELEX).
139 lution of ligands by exponential enrichment (SELEX).
140 lution of ligands by exponential enrichment (SELEX).
141 lution of ligands by exponential enrichment (SELEX).
142 olution of ligand by exponential enrichment (SELEX).
143 lution of ligands by exponential enrichment (SELEX).
144 lution of ligands by exponential enrichment (SELEX).
145 lution of ligands by exponential enrichment (SELEX).
146 lution of ligands by exponential enrichment (SELEX).
147 ion of splicing and polyadenylation by ESRP, SELEX-Seq analysis was performed, coupling traditional S
148 mers derived from combinatorial experiments (SELEX or phage display).
149 itro RNA-binding site selection experiments (SELEX) identified distinct binding motif specificities f
150 of Ligands by Exponential Enrichment (FluMag-SELEX) method to isolate a urea specific DNA aptamer wit
151 tein binding were inferred in each case from SELEX RNA sequence comparisons and confirmed by mutagene
152 o fIXa, which was previously determined from SELEX measurements.
153 ith the facile recovery of these motifs from SELEX experiments.
154 regulatory motifs, substitute for functional SELEX in most cases, and provide insights about splicing
155 We have now carried out a refined functional SELEX screen for motifs that can act as ESEs in response
156 nstrate the feasibility of employing genomic SELEX to identify vertebrate transcription factor bindin
157             Results from primer-free genomic SELEX were compared with the results from two other geno
158     After four rounds of primer-free genomic SELEX, most cloned sequences overlapped at a segment wit
159                                   In genomic SELEX, these fixed sequences may form base pairs with th
160 ared with the results from two other genomic SELEX protocols.
161                         Here, we use genomic SELEX (systematic evolution of ligands by exponential en
162            Evolution of these single-hairpin SELEX winners in plants resulted in satC that can accumu
163                                     However, SELEX is a lengthy, labor-intensive, iterative process r
164                         High-Throughput (HT) SELEX combines SELEX (Systematic Evolution of Ligands by
165            We applied these methods to an HT-SELEX experiment developing aptamers against Interleukin
166 eloped novel in-silico methods to analyze HT-SELEX data and utilized them to study the emergence of p
167 we developed a novel framework to analyze HT-SELEX data.
168  to compare output results from different HT-SELEX cycles.
169 parison of solution PCR- and ddPCR-driven HT-SELEX demonstrated that PCR method affected not only the
170 the emergence of polymerase errors during HT-SELEX.
171 to identify target-specific aptamers from HT-SELEX data and secondary structure information.
172 ms for estimating binding motifs based on HT-SELEX data.
173 published motifs estimated using the same HT-SELEX data, we demonstrate that BEESEM provides signific
174 oinformatics analysis coupled with SELEX (HT-SELEX) to thoroughly investigate the effects of initial
175 roarrays (PBM) and high-throughput SELEX (HT-SELEX), have enabled rapid measurements of the specifici
176  coupled with high-throughput sequencing (HT-SELEX), creates billions of random sequences capable of
177 extends the applicability of AptaMotif to HT-SELEX data and introduces new functionalities, as the po
178                     In this study, we use HT-SELEX derived populations to study the landscape of RNAs
179 of 239 and 56 TFs extracted from in vitro HT-SELEX binding assays and in vivo ChIP-seq data, respecti
180  focusing in spiral microfluidic channels, I-SELEX enables stringent partitioning of cells (efficienc
181              Here we use a novel strategy (I-SELEX) to discover high affinity aptamers that selective
182                    These findings validate I-SELEX as a broadly applicable aptamer discovery platform
183 et concentration, on selection efficiency in SELEX and identify strategies to control these uncertain
184                             For instance, in SELEX experiments, each urn could represent a random RNA
185 f our approach to identify binding motifs in SELEX data.
186 entification of sequence-structure motifs in SELEX-derived aptamers.
187 eic acid libraries improves success rates in SELEX experiments and facilitates the identification of
188    Target immobilization plays a key role in SELEX and other ligand enrichment methods, particularly
189  stationary phase to serve as the targets in SELEX.
190 Single-stranded DNA or RNA libraries used in SELEX experiments usually include primer-annealing seque
191 e a variety of RNA binding assays, including SELEX, to characterize the interaction in vitro and a mo
192  (ddPCR) has been recently incorporated into SELEX selection protocols to putatively reduce the propa
193 i-Mb aptamer was generated by five iterative SELEX (Systematic evolution of ligands by exponential en
194 mer for testing as a tumor-selective ligand, SELEX (systematic evolution of ligands by exponential en
195 n RNA element initially identified by CFI(m)-SELEX.
196             We present here an alternative M-SELEX method, which employs a disposable microfluidic ch
197                    Our microfluidic SELEX (M-SELEX) method exploits a number of unique phenomena that
198 t studies suggest that microfluidic SELEX (M-SELEX) technology can accelerate aptamer isolation by en
199 model to demonstrate the efficiency of the M-SELEX process, we describe here the isolation of DNA apt
200 on of ligands by exponential enrichment (MAI-SELEX), a technique designed for the efficient selection
201                                    Using MAI-SELEX, we have isolated two groups of 2'-fluoro-modified
202                            In this marriage, SELEX adds DNA specificity determination to the YSD plat
203 tspot, we used an in vitro selection method (SELEX) that revealed an 18-bp consensus sequence for Atf
204 isting of a magnetic bead-based microfluidic SELEX chip and a competitive assay chip to automate the
205                             Our microfluidic SELEX (M-SELEX) method exploits a number of unique pheno
206     Recent studies suggest that microfluidic SELEX (M-SELEX) technology can accelerate aptamer isolat
207  synthesized DNA oligonucleotides as in most SELEX studies, we utilized zebrafish genomic DNA to isol
208  in vitro randomisation experiments (namely, SELEX and phage display) reported in the literature.
209  the assignment of motifs to 200 TFs with no SELEX-derived motifs, roughly a 50% increase compared to
210               Mapped AtTopoIIA sites but not SELEX sites were strongly associated with T-DNA integrat
211                              NMR analysis of SELEX and gC sequences revealed that sequences able to b
212         At the same time, the combination of SELEX with novel sequencing technologies is beginning to
213                               Combination of SELEX-seq and genome-wide DNA binding data allows differ
214 -binding site was supported by comparison of SELEX target structure with that of the native human alp
215 chieves the full microfluidic integration of SELEX, thereby enabling highly efficient isolation of ap
216 peline to Predict the BIND: ing potential of SELEX-derived aptamers.
217 DNA sequences selected after eight rounds of SELEX were mostly G-rich, with multiple copies of CPuGGP
218  candidates were isolated in three rounds of SELEX within a total process time of approximately 10 ho
219                         After five rounds of SELEX, ETR-3 selected UG-rich sequences, in particular U
220                         After five rounds of SELEX, MBNL1 selected pyrimidine-rich RNAs containing YG
221                       Through four rounds of SELEX, we identified aptamers binding to Cry j 2.
222 ion of aptamers in the first three rounds of SELEX, while SELEX with conventional PCR failed in a num
223 tion procedure from the 4-6 weeks typical of SELEX to several days.
224 tion and further support the feasible use of SELEX RNA strategy in demonstrating the functional relev
225 ep toward expanding the power and utility of SELEX and offer an AEGIS-SELEX that could possibly gener
226 A-binding domains using a refined version of SELEX-seq.
227 ially isolated by selection-amplification or SELEX, and for locating nucleotides critical for functio
228                                   Like other SELEX methods, repeated cycles (typically 5-15) of selec
229 s is needed to understand effects on overall SELEX performance.
230 the enriched sequences, but also the overall SELEX efficiency and aptamer efficacy.
231  an experimental and computational platform, SELEX-seq, that can be used to determine the relative af
232                                         Post-SELEX optimization of one Bn-dU and one Nap-dU SOMAmer l
233 alized for the efficient and systematic post-SELEX development of aptamers for down-stream applicatio
234                                     The post-SELEX RNA obtained after 16 rounds of selection exhibite
235                                     Previous SELEX results suggested that interactions of Mnt with po
236 containing sequences present early in the R1 SELEX process to identify novel anti-p65 RNA aptamers, t
237        Adding to this uncertainty, repeating SELEX under identical conditions may lead to variable ou
238  The binding specificities of the respective SELEX RNAs were confirmed by testing their interactions
239 ed to select its optimal binding site by RNA SELEX and revealed a strong preference for the extended
240 e interactions, we have developed an RNA-RNA SELEX approach for mapping the sequences involved in int
241                                    Using RNA SELEX and bioinformatics, we identified multiple regions
242  random library using the in vitro screening SELEX approach.
243 ness in plants by in vivo genetic selection (SELEX) resulted in winning sequences that contain an H4a
244        Results of in vivo genetic selection (SELEX: systematic evolution of ligands by exponential en
245 of GTF3 to random oligonucleotide selection (SELEX) to assess their DNA binding potentials.
246 iline-based quencher via in vitro selection (SELEX).
247 an cancer previously obtained by cell-SELEX (SELEX = systematic evolution of ligands by exponential e
248  of 542 human TFs with methylation-sensitive SELEX (systematic evolution of ligands by exponential en
249 tro selection combined with deep sequencing (SELEX-seq).
250  followed by high-throughput DNA sequencing (SELEX-seq) on several floral MADS domain protein homo- a
251 s selected against cell lines using standard SELEX.
252 y an in vitro selection process, also termed SELEX (Systematic Evolution of Ligands by EXponential en
253 terial system is, however, more limited than SELEX, and some eukaryotic factors may not express or fo
254 ressed on the surface of yeast, we show that SELEX can yield binding specificity motifs and identify
255 is is, to our knowledge, the first time that SELEX is applied to a vertebrate genome.
256                                          The SELEX procedure, coupled with high-throughput sequencing
257                                          The SELEX RNAs specifically inhibited the HCV IRES function
258                                          The SELEX rounds were toggled against four pairs of aminogly
259  The mapped AtTopoIIA cleavage sites and the SELEX sites differed in their genomic distribution and a
260 nity were isolated from a RNA library by the SELEX (Systematic Evolution of Ligands by EXponential en
261 oside-aptamer recognition highlighted by the SELEX results.
262                        In vivo, however, the SELEX sites improved polyadenylation in proviral clones
263 ides and selecting for slow off-rates in the SELEX procedure, we have evolved a special class of apta
264  This putative CsrA binding site matched the SELEX-derived binding site consensus sequence in 8 out o
265             RNase footprinting of one of the SELEX RNA sequences with Mbl showed that Mbl binds both
266                             We have used the SELEX (systematic evolution of ligands by exponential en
267                   We have therefore used the SELEX method to identify RNA aptamers that recognize FAD
268                                    Using the SELEX-identified motifs to search the human genome, we i
269                                         This SELEX (systematic evolution of ligands by exponential en
270                        Consistent with this, SELEX-binding sites for the SR proteins ASF/SF2, 9G8, an
271 inding microarrays (PBM) and high-throughput SELEX (HT-SELEX), have enabled rapid measurements of the
272 s have been identified using high-throughput SELEX sequencing.
273 pensive, facile protein-matrix generation to SELEX.
274  a feature-based generalized linear model to SELEX probe counts.
275 s, encoded by the binding affinities, toward SELEX targets.
276 analysis was performed, coupling traditional SELEX with high-throughput sequencing.
277 ificity of the Dazl protein: (i) traditional SELEX and (ii) a novel tri-hybrid screen.
278 h varying genome compositions and for tuning SELEX pools to optimize the chance of finding specific f
279 sponding yeast one-hybrid system and, unlike SELEX, it does not require purification of the TF(s).
280                         Here the authors use SELEX to generate a modified DNA aptamer which specifica
281                                 Here, we use SELEX, RNA structure probing, and RNA footprinting to sh
282                                      We used SELEX (systematic evolution of ligands by exponential en
283 ral genome involved in this process, we used SELEX (systematic evolution of ligands by exponential en
284                                        Using SELEX (systematic evolution of ligands by exponential en
285                                     By using SELEX, we have obtained sets of high affinity RNA target
286                  Aptamers are selected using SELEX, Systematic Evolution of Ligands by EXponential en
287  synthesis of modified aptamer libraries via SELEX.
288 terize its tripartite consensus sequence via SELEX (systematic evolution of ligands by exponential en
289 AFF-R with nanomolar affinity using in vitro SELEX technology.
290  we characterized this role using an in vivo SELEX approach.
291 ted to in vivo functional selection (in vivo SELEX).
292             This is the first study in which SELEX targeted bacterial cells at different growth phase
293 rs in the first three rounds of SELEX, while SELEX with conventional PCR failed in a number of attemp
294 and bU nucleotides are fully compatible with SELEX, and that these analogs could be used to make boro
295 ogy and bioinformatics analysis coupled with SELEX (HT-SELEX) to thoroughly investigate the effects o
296                             SPR coupled with SELEX from the first to the last round allowed identifyi
297 ate the compatibility of this technique with SELEX.
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

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