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1 to PT2385, indicating that these effects are on-target.
2 pinal structures as is the case when walking on targets.
3 na backgrounds with altered activities based on target 35S::MIMICRY172 (MIM172), 35S::TARGET OF EARLY
4 major cellular target, leading to selective on-target accumulation of hydroxylated HIF-alpha in a co
6 mouse GPR84, both ligands acted as effective on-target activators and with high co-operativity in the
8 fied framework improves predictions for both on-target activities and off-target efficiencies of spCa
11 y compound VUF16839 (14d) combines nanomolar on-target activity (pK(i) = 8.5, pEC(50) = 9.5) with wea
12 es in the genome with relative ease, but the on-target activity and off-target effects of individual
13 s a powerful tool in genome engineering, the on-target activity and off-target effects of the system
14 ks (CNN) approach to predict Cpf1 guide RNAs on-target activity and off-target effects using their ma
17 ms located in protospacer regions can impair on-target activity as a result of mismatch tolerance.
18 tions in the FokI domain that preserved full on-target activity but showed a reduction in off-target
22 structural features that are more favored by on-target activity is the more common strategy in select
30 iagnostic methods achieved to date are based on targeted amplicon and unbiased metagenomic shotgun NG
31 ted, bead-based approach, that does not rely on target amplification or any additional signal amplifi
33 xt-generation sequencing methods have relied on target amplification prior to sequencing, introducing
35 h heart disease diagnoses, and next embarked on targeted analyses of CAD in 3893 cases and 4197 contr
42 of the PAM-sequence compatibilities and the on-target and off-target activities of Cas9 from Strepto
45 rstand how CRISPR/Cas9 discriminates between on-targets and off-targets, we have developed a single-m
47 a-high contrast by programming surface folds on targeted area with a thin optical indicator layer.
51 number of biosensor architectures that rely on target binding-induced changes in the rate of electro
52 nsor for detection of a small molecule based on target binding-induced inhibition of magnetic nanopar
54 sentation to acceptor cells and capacity for on-target binding at both cell-type-specific and tissue-
55 cleotide changes that increase efficiency of on-target binding to the inclusion of larger functional
59 their inability to migrate, plant cells rely on targeted cell division and expansion to regenerate wo
60 n repertoires of proteins directly presented on target cells and cross-presented by professional APC,
61 cific extracellular vesicle-associated cargo on target cells have stoked interest in extracellular ve
64 classes, reducing chemokine receptor levels on target cells or eliminating competent chemokine recep
65 Env) of HIV-1 to CD4 and chemokine receptors on target cells triggers refolding of the gp41 transmemb
66 okines that are up to 1,000-fold more potent on target cells, allowing specific signaling in selected
67 inating cells, as well as vesicle deposition on target cells, depend on interactions with macrophages
68 the loss of host-encoded inhibitory ligands on target cells, including MHC class I (MHC-I) molecules
69 y which the HH signal is received by patched on target cells, transduced across the cell membrane by
70 urveillance for signatures of "altered self" on target cells, via a membrane-linked gammadelta TCR re
75 tive binding profile of 24 was translated to on-target cellular activity in model lymphoma cell lines
77 over-activation, we present a strategy based on targeting complexes of D(1)R and histamine H(3) recep
78 target test tube contains a set of desired "on-target" complexes, each with a target secondary struc
88 This review presents some recent research on targeted delivery for cancer therapy and also discuss
89 ws them with additional characteristics like on-target delivery, and conjugation with immunotherapeut
90 ategy will inspire new insights and thoughts on targeting design and will speed up precision medicine
91 e activity of thousands of guides, we refine on-target design rules and develop a comprehensive set o
92 d ligands) in the fabrication process limits on-target design, impeding material diversity and availa
94 on-toxic and inactive until brought together on target DNA by adjacently bound programmable DNA-bindi
97 f-target RNA-editing activity and comparable on-target DNA-editing activity that are also among the s
98 ificant GDMT opportunities, with no patients on target doses of beta-blocker, sacubitril/valsartan, a
101 potential to use PROTAC technology to reduce on-target drug toxicities and rescue the therapeutic pot
102 -target DNA editing while maintaining robust on-target editing at most positions targetable by canoni
103 duces off-target mutagenesis while retaining on-target editing efficiencies with Cas9 and base editor
106 t, H122A, R33A]) that display comparable DNA on-target editing frequencies, whilst eliciting a 12- to
107 We optimize conditions for selection-free on-target editing in patient-derived HSCs as a nearly co
109 ur results reveal high frequency (up to 90%) on-target editing with no evidence of off-target cleavag
110 s with minimal optimization while preserving on-target editing, and they can be multiplexed to suppre
113 tent immunological activity, not only as an "on-target effect" originating within irradiated cancer c
115 rentiated chemical series is consistent with on-target effects posing significant challenges to the c
116 d alleles generated by CRISPR, as unintended on-target effects that fail to be detected by simple PCR
118 (sgRNAs) in 6 cells lines and show that the on-target efficacies are comparable, but CRISPR technolo
119 D2006 (AsCpf1 and LbCpf1, respectively) have on-target efficiencies in human cells comparable with th
120 However, testing gene editing strategies for on-target efficiency and off-target events using persona
124 ficant effects on clinical symptoms, but not on target engagement, suggesting a higher dose may yet b
126 Next-generation sequencing was performed on target enriched sequence libraries prepared directly
127 uman papillomavirus (HPV) typing assay based on target enrichment and whole-genome sequencing (eWGS).
130 Replipore sequencing, has the potential for on target examination of DNA replication in a wide range
138 ll rates of cleavage and activity versus the on-target gene in cells and in mice were only minimally
139 ty SpyCas9 that maintained the same level of on-target gene modification, the off-target effects incl
140 ncoKB, TP53 mutations based on their effects on target-gene transactivation, effects of cancer mutati
142 increases p27-cJun recruitment to and action on target genes to drive oncogenic pathways and repress
146 ness problem after CRISPR-Cas treatment, and on-target genome editing side effect in undesired tissue
151 evelopment of antimicrobial strategies based on targeting host mitochondrial metabolism independent o
152 Using immunodeficient SCID mice, we focused on targeting human brain tumors with these VSV-EBOVs.
153 ntially outperforms previous scoring methods on target identification on HIP and HOP assays, respecti
158 ivo pharmacokinetic profiles and show potent on target inhibition of eIF4E phosphorylation in cells.
161 gene editing rates, and effectively reduces on-target insertion and deletion rates in knock-in appli
162 evidence for an antimetastatic therapy based on targeting integrin beta3 (beta3), which is selectivel
163 evaluate the current state of the literature on targeted interventions in higher education with an ey
164 r drug development efforts have been focused on targeting it, most notably by inhibiting its AURKB ki
165 600 plasmids and 1700 fly lines with a focus on targeting kinases, phosphatases and transcription fac
166 nces in transgenic Populus trichocarpa based on targeted knockdowns of specific monolignol genes.
168 ueing face; (2) effects of target congruency on target-locked N1 and P3 were modulated by gaze conver
170 delines for control of schistosomiasis based on targeted mass drug administration (MDA) and, in 2017,
171 oprotein (HDL) apolipoproteomic score, based on targeted mass spectrometry of HDL-associated apolipop
173 of timely therapeutic intervention(s) based on targeting mediators or pathways that influence I/R in
174 ecreted as soluble monomers that oligomerize on target membranes in the so-called prepore state; afte
175 enhanced, an effect that is believed to rely on targeted memory reactivation (TMR) induced by the sen
177 agement strategies should additionally focus on targeting metabolic components, including weight mana
178 help developing therapeutic strategies based on targeting metabolism to ameliorate deficits in effort
179 Investigation of the Hct variation effect on target metabolites revealed that it affected the conc
181 the present work, we propose a method based on targeted metabolomics to identify the polyphenols pre
184 Argonaute-catalysed endonucleolytic cleavage on target mRNAs at various sites within partially paired
189 nd its detection methods with specific focus on targeting native collagens as well as denatured colla
191 ation of the LC has more specific influences on target networks than had initially been imagined.
195 st combination therapies are developed based on targets of existing drugs, which only represent a sma
197 eltaT cells may offer the potential to avoid on-target, off-tumor toxicity and allo-reactivity in the
198 issues to demonstrate that both efficacy and on-target, off-tumor toxicity can be studied in our prec
200 umour-associated antigens (TAAs) can lead to on-target-off-tumour toxicity and to resistance, owing t
201 treatment of NPM1c(+)HLA-A2(+) AML may limit on-target-off-tumour toxicity and tumour resistance.
202 positive HCC cells and does not cause severe on-target/off-tumor toxicity in a human CD147 transgenic
206 mains, but the effects of these interactions on targeting or protein mobility are elusive so far.
207 been ascribed to largely mutually exclusive on-target or off-target mechanisms in which tumors eithe
209 can help to quickly identify new promising (on-target) or unintended (off-target) effects of drugs.
210 proteins) would have a negligible impact on on-target organisms in the guilds or predators and paras
211 e sex steroid concentrations and bioactivity on target organs in mice expressing a human SHBG transge
212 l stiffness, the impact of aortic stiffening on target organs, noninvasive methods for the measuremen
215 Here we describe a novel workflow based on targeted phenotypic culturing linked to large-scale w
219 ur findings suggest that chromatin access of on-target pioneer factors is primarily driven by the pro
220 nd task in which choices could only be based on target positions, participants consistently chose amo
222 We investigate two types of multi-targets: on-targets predicted through perfect sequence complement
223 (gRNA) scaffold and the development of gRNA on-target prediction algorithms, have since been made to
224 verreliance of the perceptual choice circuit on target preferring neurons and a failure to appropriat
225 urgent prioritisation of programmes focused on targeted prevention, early identification, and effect
226 rrently, there are two main approaches based on target/probe hybridization reported in the literature
227 resulted in decreased HIF-1alpha enrichment on target promoters and lower expression of select HIF-1
229 ntly bind to amino acids other than cysteine on target proteins such as glutathione S-transferase pi
230 Proteome-wide detection of SUMOylation sites on target proteins typically requires ectopic expression
231 ential inhibitory effects of these molecules on target proteins were investigated using docking and m
233 beta-N-acetylglucosamine to Ser/Thr residues on target proteins, is increasingly recognized as a crit
234 palmitoyl-CoA, to specific cysteine residues on target proteins, which affects their stability, local
237 and complex gibberellin (GA) response relies on targeted proteolysis of DELLA proteins mediated by a
238 wever, this requires rapid identification of on-target reads while most mapping methods require compu
240 can be greatly improved in assays dependent on target recognition by pairs of antibodies using in si
241 died in the paediatric setting, with a focus on target relevance, available efficacy and safety data,
242 o-laryngeal movement during swallowing based on targets required for closing the hyo-laryngeal area f
245 ages of visual objects had a dramatic effect on target selection, acting much like spatial cues used
246 egies to overcome these challenges, focusing on target selection, polypharmacology, and personalized
248 -capture using TBD probes generates a modest on-target sequencing ratio, while two successive rounds
249 l inhibitors of PERK's kinase activity cause on-target side effects that have precluded their further
252 ression of imprecise editing outcomes at the on-target site as key design parameters that control the
253 enrichment in co-occupancy with PBX proteins on target sites and exists in the same complex with PBX
254 ning the transcription factor residence time on target sites.Both transcription binding kinetics and
255 ons/deletions (indels) can result in altered on-target sites and novel potent off-target sites, which
256 characterize unintended larger deletions at on-target sites that frequently evade common genotyping
260 ting directly from whole blood, assays based on target-specific polymerase chain reaction or metageno
261 ecreased off-target delivery without loss of on-target specificity, and greater immunological stealth
264 H NMR-based metabolomics analysis is focused on targeted studies related to concentrations of the sma
266 terminal domain of IL-33 to its receptor ST2 on targets such as CD4(+) Th2 cells, ILC2, and mast cell
269 erapy, melanoma treatment is currently based on targeting the BRAF/MEK/ERK signaling pathway and immu
270 ent of novel AD therapeutic strategies based on targeting the D-isomerized Abeta, rather than natural
272 e iron by lysing erythrocytes, which depends on targeting the host receptor Duffy antigen receptor fo
273 o eradicate these tumors focus predominantly on targeting the proliferation of rapidly growing cancer
276 these results suggest that closing the door on targeting the type 1 IFN pathway in SLE may be premat
277 arch proposes a combinatorial approach based on targeting the very mechanisms of resistance to gemcit
278 days, the number of clinical trials focusing on targeted therapies for uncommon drivers is growing ex
279 mplications for heritability, but its impact on targeted therapies has not been fully appreciated.
285 formation that could inform treatments based on targeting these distinct molecules that define TRPM4
287 hanisms by which these immune cells converge on target tissues, interact with fibroblasts and promote
289 targeted therapies are usually secondary to "on target toxicities." Management is largely supportive
291 emplify this paradigm shift, but intolerable on-target toxicities in more prolific normal tissues hav
292 er, many MEK inhibitors are limited owing to on-target toxicities(5-7) and drug resistance(8-10).
295 studies in model organisms have raised some on-target toxicity concerns(5-8), the biological consequ
296 n resistance mechanism is the acquisition of on-target TRK kinase domain mutations, which interfere w
299 t formulations cannot retain fire retardants on target vegetation for extended periods of time throug