ライフサイエンスコーパス: on-target

1 proprioceptors in the neck, to keep the head on target.

2 pinal structures as is the case when walking on targets.

3 itatory inputs, and form fewer release sites on targets.

4 na backgrounds with altered activities based on target 35S::MIMICRY172 (MIM172), 35S::TARGET OF EARLY

5 dies suggesting that KPT-330 efficacy relies on targeting abundantly expressed XPO1, followed by the

6 major cellular target, leading to selective on-target accumulation of hydroxylated HIF-alpha in a co

7 SpCas9-HF1 retains on-target activities comparable to wild-type SpCas9 with

8 ervations that different sgRNAs have varying on-target activities.

9 r class as well as demonstration of cellular on target activity of the most potent and selective inhi

10 eate optimized sgRNA libraries that maximize on-target activity and minimize off-target effects to en

11 es in the genome with relative ease, but the on-target activity and off-target effects of individual

12 genome-wide specificity without compromising on-target activity in human cells.

13 Despite on-target activity in small-diameter dorsal root ganglia

14 A small-molecule SERCA inhibitor has on-target activity in two mouse models of human leukemia

15 structural features that are more favored by on-target activity is the more common strategy in select

16 A powerful way to enhance ON-target activity of therapeutic T cells is to engineer

17 Despite pharmacodynamic evidence for robust on-target activity, the compounds exhibited modest, thou

18 off-targeting while maintaining the intended on-target activity.

19 mitoses and cellular ploidy, consistent with on-target activity.

20 ti-obesity drug development is thus focusing on targeting adipocytes that store excess fat.

21 of PI3K/mTOR signaling resulted in multiple on-target adverse events.

22 h the majority of discovery programs focused on targeting allosteric sites, with allosteric ligands n

23 on on the food intake side is mainly focused on target analysis.

24 Laboratory studies on target analytes showed that the ionization conditions

25 We include studies on target and nontarget species, with an emphasis on qua

26 ib showed benefits that might depend on both on-target and immunological off-target effects.

27 RNAs, though the variables that control its on-target and off-target activity remain poorly characte

28 with Cas9 mRNA and single guide RNAs induces on-target and off-target mutations that are transmissibl

29 Graphical visualization of on-target and off-target sites in the genome is provided

30 ndonuclease-associated adverse effects, both on-target and off-target; and oncogene activation caused

31 The relationship among H3 IA dose, time on target, and peripheral pharmacokinetics was further i

32 erapeutic regimens for prostate cancer focus on targeting androgen receptor (AR) signaling.

33 cine formulations, which are currently based on targeting antigens such as the circumsporozoite prote

34 Although prior work has focused on targeting AR directly, co-activators of AR signaling,

35 fects on the gut are described, with a focus on targets at the level of the epithelium.

36 eins will complement and potentially improve on targeting Bcl-2 protein interactions with BH3 mimetic

37 nsor for detection of a small molecule based on target binding-induced inhibition of magnetic nanopar

38 Whilst most focus has been on targeting binding-site cysteine residues, targeting n

39 cally limited for this indication because of on-target bradycardia as a serious adverse effect.

40 The on-target cardiotoxic effects of trastuzumab were owing

41 racellular vesicles that move to the synapse on target cell contact.

42 in the extracellular milieu and multimerize on target cell membranes.

43 we show that GzmB-activated p53 accumulates on target cell mitochondria and interacts with Bcl-2.

44 enicity influenza A viruses (LP IAVs) depend on target cell proteases to cleave their viral glycoprot

45 Heparan sulfates on target cell surfaces can act as receptors for exosome

46 viruses, these proteases are known to reside on target cell surfaces.

47 s to CD40, leading to many effects depending on target cell type.

48 s of this mode of epithelial cell plasticity on targeted cell lysis by cytotoxic T lymphocytes (CTL).

49 inds either sialic acid or protein receptors on target cells and a trimeric fusion protein (F) that m

50 decreased activation of EGF receptor (EGFR) on target cells and, eventually, dampening a positive EG

51 2/3 and NK group 2, member D (NKG2D) ligands on target cells by a mechanism involving c-Myc induction

52 oxin from Pseudomonas aeruginosa, Tse6, acts on target cells by degrading the universally essential d

53 erapy, and the recognition of "missing-self" on target cells is crucial for promoting NK cell-mediate

54 ulfate on exosomes captures fibronectin, and on target cells it acts as a receptor for fibronectin.

55 classes, reducing chemokine receptor levels on target cells or eliminating competent chemokine recep

56 ind to G protein-coupled receptors expressed on target cells to initiate signaling cascades and induc

57 ring activation that bind specific receptors on target cells to mediate effects; (ii) the multimolecu

58 ited meandering trajectories, and stabilized on target cells to which they delivered membraneous vesi

59 IL-17, a proinflammatory cytokine that acts on target cells via a heterodimeric receptor formed by I

60 form multivalent antigen-antibody complexes on target cells were key determinants of ADCC potency, w

61 okines that are up to 1,000-fold more potent on target cells, allowing specific signaling in selected

62 inating cells, as well as vesicle deposition on target cells, depend on interactions with macrophages

63 gement can facilitate receptor cross-linking on target cells, or induce retrograde FcgammaR signals t

64 cues and act via cognate cytokine receptors on target cells, stimulating specific intracellular sign

65 to Axl, a receptor tyrosine kinase expressed on target cells.

66 ls and their ligands, HLA class I molecules, on target cells.

67 mechanisms of LPA generation and how it acts on target cells.

68 diseases, and exert a wide range of effects on target cells.

69 ects sphingosine-1-phosphate (S1P) signaling on targeted cells that bear the S1P receptors S1P1, S1P3

70 gineered a TALEN variant that exhibits equal on-target cleavage activity but tenfold lower average of

71 etween sequence features of sgRNAs and their on-target cleavage efficiencies remains limited, largely

72 educe off-target effects and maintain robust on-target cleavage.

73 on ability should show a U-shaped dependency on target-clutter similarity, which is confirmed experim

74 target test tube contains a set of desired "on-target" complexes, each with a target secondary struc

75 , producing a steep, higher-order dependence on target concentration.

76 reconstruction was generated, growth screens on targeted conditions of interest were performed, and c

77 Here we develop AcTakines (Activity-on-Target cytokines), optimized (mutated) immunocytokine

78 nanoparticle shape at different size regimes on targeting, cytotoxicity, and cellular mechanics.

79 nates responses throughout development based on targeted degradation of plant-specific transcriptiona

80 n intermingle or occupy separate territories on target dendrites.

81 eves 95% SNP detection sensitivity at a mean on-target depth of 40 reads, whereas WGS only requires a

82 guals showed similar behavioural performance on target detection presented in words and nonwords, sug

83 crease off-target cleavage without affecting on-target disruption in 293T cells.

84 re heterogeneous and their structure depends on target-distractor distance.

85 nt antitumor activity, which relied entirely on targeting Dll4 expressed by tumor stromal cells but n

86 es allow for proper control of toxicity from on-target DNA damage.

87 ion in developing lymphocytes by generating "on-target" DNA breaks at matched pairs of bona fide reco

88 On-target drug delivery remains a challenge in cancer pr

89 In cultured cells, RGNs on-target editing activity had been varied when gRNAs wa

90 tion of HF-BE3, while maintaining comparable on-target editing levels.

91 the amount of guide RNA with a reduction in on-target editing.

92 tent immunological activity, not only as an "on-target effect" originating within irradiated cancer c

93 block infection, independent of the intended on-target effect.

94 ed cells, its use in vivo has a deleterious "on target" effect on liver and kidney function.

95 secretion and can exert a genomic footprint on target effector T (Teff) cells.

96 Current lead compounds 4 and 5 exhibit on-target effects by specifically blocking the MARV VP40

97 rmacogenetic approaches to separate specific on-target effects from nonspecific off-target effects.

98 Together, these data validate on-target effects of BTK inhibition in the tissue compar

99 wever, recent studies have shown deleterious on-target effects of systemic TGR5 agonists.

100 rentiated chemical series is consistent with on-target effects posing significant challenges to the c

101 nds has been hampered owing to their adverse on-target effects.

102 (sgRNAs) in 6 cells lines and show that the on-target efficacies are comparable, but CRISPR technolo

103 aks, but there are few known rules governing on-target efficacy of this system.

104 an be designed as biased agonists to promote on-target efficacy without on-target side effects.

105 D2006 (AsCpf1 and LbCpf1, respectively) have on-target efficiencies in human cells comparable with th

106 arameters for the design of sgRNAs with high on-target efficiencies, especially in the context of hig

107 We also evaluate on-target efficiency prediction algorithms against avail

108 data from our labs, we find that the optimal on-target efficiency prediction model strongly depends o

109 the sgRNA are significantly correlated with on-target efficiency.

110 ously reported CAR T cell studies only focus on targeting EGFRvIII.

111 diets may exceed the expected benefits based on targeting either risk factor alone.

112 Next-generation sequencing was performed on target enriched sequence libraries prepared directly

113 uman papillomavirus (HPV) typing assay based on target enrichment and whole-genome sequencing (eWGS).

114 scuss potential new therapies that are based on targeting ERG.

115 the effect of this relevance-based shifting on target-evoked brain activity was dissociable from the

116 ncy of miRNA family members and their impact on target expression in an in vivo setting.

117 of ADC in vivo can be hard to predict based on target expression pattern alone.

118 fect that Argonaute scarcity conditions have on target expression variation.

119 ective clear cell renal cell carcinoma in an on-target fashion.

120 er's center-of-mass will facilitate stepping on target footholds.

121 evidence and provide much-needed information on targets for effective interventions.

122 re an enzyme from one canonical pathway acts on targets from other pathways.

123 y one agonist or modulator from another, but on-target from off-target receptor or functional pathway

124 ts and to predict their pathological effects on target gene expression for clinical purposes.

125 nhibitor blocked effects of CREB acetylation on target gene expression, our results demonstrate how c

126 binding sites that have a significant impact on target gene expression.

127 to DXR; however, this binding had no effect on target gene expression.

128 Interestingly, the effect of feedback on target gene induction is greatly reduced when the str

129 interacts with TFIID to facilitate assembly on target gene promoters remains elusive.

130 he point of transcriptional complex assembly on target gene promoters.

131 zation and requires the canonical AP-1 sites on target gene promoters.

132 8 to compete with E2F2 for E2f-binding sites on target gene promoters.

133 s been sequenced, to date there is no report on targeted gene deletion in U. virens and no molecular

134 results indicate the importance of balancing on-target gene cleavage potency with off-target effects:

135 The increase in on-target gene editing is locus-independent and specific

136 izing hPSCs in G2/M with ABT phase increases on-target gene editing, defined as correct targeting cas

137 m of phenotypic outcomes due to differential on-target gene suppression or perturbation of off-target

138 Yki and its binding partner, Scalloped (Sd), on target-gene promoters and is essential for Yki to dri

139 Control by PTF1A is direct on target genes and indirect through a ten-member transc

140 , but the activity of Smads and their impact on target genes are further regulated by a wide variety

141 t the relatively subtle effects of microRNAs on target genes can have broad effects in developmental

142 ically active SRF, but enhanced SRF activity on target genes involved in proliferation.

143 ely expressed repressive E2F4/p130 complexes on target genes upon EWS-FLI1 modulation.

144 biological activities and regulatory effects on target genes, however, enhancers should be further cl

145 blocks, with highly context-specific effects on target genes.

146 that interact with steroid response elements on target genes.

147 approach for studying brain circuits relies on targeting genetically encoded sensors and effectors t

148 es by 5,000-fold or more without sacrificing on-target genome editing efficiencies.

149 Based on targeted glycine substitutions in the Env fusion mach

150 re genotype accuracy by the concordance with on-target GWAS genotypes and between 80 pairs of sequenc

151 Here, we report efficient, on-target, homology-directed repair (HDR) editing of the

152 ntially outperforms previous scoring methods on target identification on HIP and HOP assays, respecti

153 ion and explore the impact of these findings on target identification.

154 blood-induced joint damage warrants studies on targeting IL-1beta to potentially prevent joint degen

155 Focusing on targeted immuno-modulation, we describe local deliver

156 On target in vivo coverage of PDE10A in rat brain was as

157 esions, implicating its enzyme activity acts on targets in the focal adhesion complex.

158 of these hyperactive hippocampal projections on targets in the limbic neocortex could contribute to c

159 ng PD-L1E-bearing lymphocytes, suggesting an on-target in vivo effect of pidilizumab.

160 Ly49 receptors can bind to MHC class I on targets (in trans) and also to MHC class I on the NK-

161 is 50-fold lower than existing assays based on target-induced conformational change.

162 ossessing antitumor activity consistent with on-target inhibition of cell cycle CDKs.

163 This reflects on-target inhibition of the ATP1A1 Na(+)/K(+) pump, whic

164 or of EZH2 and EZH1, demonstrating UNC1999's on-target inhibition.

165 PD was an on-target inhibitor of RB phosphorylation and blocked G1

166 wn about the impact of entrapment neuropathy on target innervation and the relationship of nerve fibr

167 the underpinning biophysical science, based on targeted input from expert research communities and o

168 or into neonatal and adult mice and achieved on-target integration into approximately 0.5% of the alb

169 e established that F9 was produced only from on-target integration, and ribosomal skipping was highly

170 evidence for an antimetastatic therapy based on targeting integrin beta3 (beta3), which is selectivel

171 evaluate the current state of the literature on targeted interventions in higher education with an ey

172 in alloreactive T cells, but lead to severe on-target intestinal toxicity.

173 r drug development efforts have been focused on targeting it, most notably by inhibiting its AURKB ki

174 ia and thrombocytopenia thought to be due to on-target JAK2 inhibition.

175 31, 2014, were selected for inclusion based on targeted keyword searches, manual review of bibliogra

176 increase in IC50) by the modification, while on-target knockdown was improved (2-fold reduction in IC

177 ologic therapy without cardiotoxicity, based on targeting KV11.1.

178 ntroducing highly electron-withdrawing atoms on targeted ligands, the energy barrier was significantl

179 ple the observed antitumor efficacy from the on-target liver toxicity.

180 and growth of SHH-subgroup MB in vivo, in an on-target manner, leading to increased survival.

181 f hCD27 are consistent with previous reports on targeting mCD27 and provide a rationale for the clini

182 ve with dominant-negative MK2, suggesting an on-target mechanism of action.

183 of serum, and demonstrates highly specific, on-target mechanism of action.

184 cts of siRNAs are unrelated to the intended "on-target" mechanism, defined by full complementarity of

185 mitochondrial apoptosis pathway, suggesting on-target mechanisms.

186 ecreted as soluble monomers that oligomerize on target membranes in the so-called prepore state; afte

187 ssembly of a 2:1 syntaxin-1a:SNAP-25 complex on target membranes that kinetically alters the binding

188 is-regulatory iron-responsive elements (IRE) on target messenger RNAs (mRNA).

189 s, it is important to focus research efforts on targeting mitochondrial dysfunction in the failing he

190 of genetic disease mechanisms relies mostly on targeted mouse mutants that are derived from engineer

191 binding to partially complementary sequences on target mRNA transcripts, thereby causing their degrad

192 complex, but the molecular events that occur on target mRNAs are poorly resolved.

193 Argonaute-catalysed endonucleolytic cleavage on target mRNAs at various sites within partially paired

194 downstream machinery with time of residence on target mRNAs.

195 proteins by stalling ribosomal translocation on target mRNAs.

196 y control (QC) method suitable for DIA based on targeted MS/MS acquisition is detailed.

197 es, and provides a simple method to increase on-target mutagenesis in plants using CRISPR/Cas9.

198 els where off-target mutagenesis is low, but on-target mutagenesis remains relatively high.

199 nd its detection methods with specific focus on targeting native collagens as well as denatured colla

200 The on-target nature of findings was evaluated in Indiana P-

201 ronology of drug discovery campaigns focused on targeting Nek2.

202 tes an acute direct excitatory effect of PDF on target neurons to control neuronal output.

203 n tissues, leading to the discovery of 2,556 on-target, novel transcripts.

204 ss spectrometry and olfactometry (MDGC-MS-O) on targeted odorant fractions.

205 s ATP synthase subunit beta and is dependent on target of rapamycin (TOR) downstream.

206 vo efficacy across the NCLs with an emphasis on targets of action.

207 ven by CpG methylation converges exclusively on targets of the Polycomb repressive complex 2 which re

208 shared antigens has the potential to lead to on-target off-tumor toxicities, as observed in recent tr

209 the treatment is associated with prolonged "on-target off-tumor" toxicities due to the targeted elim

210 tumor burden; however, in rare cases, lethal on-target/off-tumor effects have been reported.

211 ved residues in the ectodomain has no effect on targeting or fusion, although short deletions that in

212 mains, but the effects of these interactions on targeting or protein mobility are elusive so far.

213 been ascribed to largely mutually exclusive on-target or off-target mechanisms in which tumors eithe

214 inate irradiated cancer cells, either as an "on-target" or as on "off-target" effect.

215 tecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from ta

216 proteins) would have a negligible impact on on-target organisms in the guilds or predators and paras

217 e sex steroid concentrations and bioactivity on target organs in mice expressing a human SHBG transge

218 however, remain unclear and differ depending on target organs.

219 ft cancer models, with a high correlation to on-target pharmacodynamic activity, and possesses favora

220 monstrate arbitrary single-qubit gates based on targeted phase shifts, an approach that can be applie

221 Here we describe a novel workflow based on targeted phenotypic culturing linked to large-scale w

222 Ascl1 acts as an "on-target" pioneer factor by immediately occupying most

223 the goal of malaria elimination will depend on targeting Plasmodium pathways essential across all li

224 hs, we did country-by-country analyses based on target population, incremental coverage increase, and

225 nd task in which choices could only be based on target positions, participants consistently chose amo

226 A sequences that are optimized for both high on-target potency and low off-target effect.

227 Compound 31 displayed improved LipE and on-target potency in both biochemical and cellular reado

228 reducing off-targeting without jeopardizing on-target potency.

229 (gRNA) scaffold and the development of gRNA on-target prediction algorithms, have since been made to

230 urgent prioritisation of programmes focused on targeted prevention, early identification, and effect

231 ls, attachment of both moieties is dependant on target-probe hybridisation straightening the loop.

232 resulted in decreased HIF-1alpha enrichment on target promoters and lower expression of select HIF-1

233 rostate, activating E2F3 cooperates with ETS on target promoters.

234 ls significantly alter the activity of NR2F2 on target promoters.

235 n cell are the prerequisite for its function on target protein.

236 sferred ubiquitin to surface exposed lysines on target proteins and even catalyzed the formation of b

237 s that mediate binding to acetylated lysines on target proteins to regulate gene expression.

238 Proteome-wide detection of SUMOylation sites on target proteins typically requires ectopic expression

239 oactive labeling to characterize methylation on target proteins.

240 enzymes, and the effect of this modification on target proteins.

241 At a mean on-target read depth of 20X, commonly used for rare dise

242 in batches of 48 generated, on average, 81% on-target reads per sample and 100% genome coverage with

243 -sequencing experiments can be combined with on-target reads to accurately estimate the ancestry of e

244 can be greatly improved in assays dependent on target recognition by pairs of antibodies using in si

245 the potential to cause lethal toxicity from on-target recognition of normal tissues, and there is a

246 o-laryngeal movement during swallowing based on targets required for closing the hyo-laryngeal area f

247 ing next-generation inhibitors to circumvent on-target resistance mechanisms, as well as ongoing stra

248 nstead function by increasing the dwell time on target RNA.

249 ranscriptional signature was concurrent with on-target RNA reduction and preceded transaminitis.

250 Through its actions on target RNAs, AUF1 preserves genomic integrity, in agr

251 O) proteins to partially complementary sites on target RNAs.

252 ability to perform in situ chemical analysis on target samples in their native states in the undistur

253 g TF dynamics and influence of the epigenome on target search parameters.

254 analysis to evaluate the effects of isomiRs on target selection.

255 and frailty, therapeutic opportunities based on targeting senescent cells and the SASP, and potential

256 Striking on-target sensitivity was achieved with the BCL2-specifi

257 lly by designing oligos that do not have any on-target sequence match at all, yet can strongly reprod

258 ng optimization increased the yield of total on-target sequencing data 2-fold compared to the previou

259 ry DNA architectures autonomously based only on target shape.

260 otection in ischemic tissue while minimizing on-target side effects associated with NMDAR blockade in

261 l inhibitors of PERK's kinase activity cause on-target side effects that have precluded their further

262 onists to promote on-target efficacy without on-target side effects.

263 designing pathway-specific drugs that avoid on-target side effects.

264 Current approaches to cancer treatment focus on targeting signal transduction pathways.

265 higher than) those observed at the intended on-target site.

266 ning the transcription factor residence time on target sites.Both transcription binding kinetics and

267 ons/deletions (indels) can result in altered on-target sites and novel potent off-target sites, which

268 leosomes affect Cas9 binding and activity at on-target sites, but their impact at off-target sites is

269 peak, but generally at lower rates than the on-target sites.

270 ce of microRNA seeds instead of the intended on-target space of protein-coding genes.

271 factors: conservation effectiveness (impact on target species), private costs (especially reductions

272 culated according to type of new agent based on target specificity.

273 he SPIM imaging arm, we were able to improve on targeting speed and precision.

274 eveloped an immunostimulatory strategy based on targeted Stat3 silencing in Toll-like receptor 9 (TLR

275 cts hippocampal dynamics and their influence on target structures, such as ventral striatum.

276 and high-quality graphene patterns directly on target substrates, which opens a door for fabricating

277 beam processing, UV exposure, or wet etching on target substrates.

278 The P3 amplitude was larger for probes on targets than on distractors, regardless of whether at

279 rat neonatal cardiac myocytes was dependent on targeting the AKAP5-PKA complex to the C-terminal tai

280 ety of preclinical models, generally focused on targeting the diseased locus itself; however, limited

281 is of recent drug discovery efforts has been on targeting the epigenome, including DNA methylation an

282 sease-modifying treatment for epilepsy based on targeting the P2X7 receptor.

283 on successful treatment of symptoms but also on targeting the pathological mechanisms of disease, ide

284 ilitate therapeutic interventions that focus on targeting the PLK1-mediated and/or FoxM1-mediated sig

285 o eradicate these tumors focus predominantly on targeting the proliferation of rapidly growing cancer

286 , but realizing their full potential depends on targeting the sensor to distinct cell types.

287 We focused our ZFN approach on targeting the type 2 vertebrate-like cryptochrome gen

288 of novel biomarkers, and increased emphasis on targeting therapies toward physiological basis of dis

289 C that should be considered in future trials on targeted therapy and monitoring of response.

290 ading to emerging treatment strategies based on targeted therapy.

291 for ACT and how to manage expected off-tumor/on-target toxicities.

292 y tumor-specific targets to avoid off-tumor, on-target toxicity.

293 ng the effect of these multiple variant SNPs on target transcript levels has been a major challenge.

294 The effects on target transcript levels tend to be modest and can be

295 al thermogenesis and support a renewed focus on targeting UCP3 in metabolic physiology.

296 ic interventions in FXS have focused largely on targets upstream of translational control to normaliz

297 Despite the millions of dollars spent on target validation and drug optimization in preclinica

298 Controlling siRNA on-target versus microRNA (miRNA)-like off-target potenc

299 ome of these advances, with special emphasis on target volume and organ-at-risk delineation, use of m

300 nesis and minimizing wasted animal husbandry on targets with poor activity.