Abstract：
:An accurate prediction of the outcome of a given drug treatment requires quantitative values for all parameters and concentrations involved as well as a detailed characterization of the network of interactions where the target molecule is embedded. Here, we present a high-throughput in silico screening of all potential networks of three interacting nodes to study the effect of the initial conditions of the network in the efficiency of drug inhibition. Our study shows that most network topologies can induce multiple dose-response curves, where the treatment has an enhanced, reduced or even no effect depending on the initial conditions. The type of dual response observed depends on how the potential bistable regimes interplay with the inhibition of one of the nodes inside a nonlinear pathway architecture. We propose that this dependence of the strength of the drug on the initial state of activation of the pathway may be affecting the outcome and the reproducibility of drug studies and clinical trials.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Doldán-Martelli V,Míguez DGdoi
10.1038/s41598-018-30913-9subject
Has Abstractpub_date
2018-08-21 00:00:00pages
12495issue
1issn
2045-2322pii
10.1038/s41598-018-30913-9journal_volume
8pub_type
杂志文章abstract：:CRISPR-Cas9/gRNA exhibits therapeutic efficacy against latent human immunodeficiency virus (HIV) genome but the delivery of this therapeutic cargo to the brain remains as a challenge. In this research, for the first time, we demonstrated magnetically guided non-invasive delivery of a nano-formulation (NF), composed of...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-019-40222-4
更新日期：2019-03-08 00:00:00
abstract：:Thermal rectifiers whose forward heat fluxes are greater than reverse counterparts have been extensively studied. Here we have discovered, idealized, and derived the ultimate limit of such rectification ratios, which are partially validated by numerical simulations, experiments, and micro-scale Hamiltonian-oscillator ...
journal_title：Scientific reports
pub_type： 杂志文章
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更新日期：2015-08-04 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
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更新日期：2020-12-03 00:00:00
abstract：:A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper. ...
journal_title：Scientific reports
pub_type： 已发布勘误
doi：10.1038/s41598-018-26061-9
更新日期：2018-05-15 00:00:00
abstract：:Yield-phenology relation is a critical issue affecting rainfed maize field productivity in semiarid east African Plateau (EAP). We first introduced Chinese ridge-furrow mulching (RFM) system to EAP, using three maize cultivars with early-, mid- and late-maturing traits as test materials. A two-year field experiment wa...
journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/s41598-017-03372-x
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journal_title：Scientific reports
pub_type： 杂志文章
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更新日期：2020-09-11 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
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更新日期：2016-11-08 00:00:00
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pub_type： 杂志文章
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journal_title：Scientific reports
pub_type： 杂志文章
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更新日期：2013-10-29 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
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更新日期：2018-06-20 00:00:00
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pub_type： 杂志文章
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更新日期：2020-02-06 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
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更新日期：2016-02-02 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
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更新日期：2015-05-20 00:00:00
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journal_title：Scientific reports
pub_type： 杂志文章
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更新日期：2019-09-24 00:00:00
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pub_type： 杂志文章
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journal_title：Scientific reports
pub_type： 杂志文章
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更新日期：2019-10-16 00:00:00
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pub_type： 杂志文章
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journal_title：Scientific reports
pub_type： 杂志文章
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更新日期：2017-06-01 00:00:00
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journal_title：Scientific reports
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更新日期：2017-04-03 00:00:00
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journal_title：Scientific reports
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journal_title：Scientific reports
pub_type： 杂志文章
doi：10.1038/srep34463
更新日期：2016-10-03 00:00:00
