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Filename: drivers/Session_files_driver.php
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Function: require_once
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Filename: Session/Session.php
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Function: require_once
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Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
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Function: _error_handler
File: /var/www/html/index.php
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Function: require_once
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Filename: controllers/Detail.php
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Backtrace:
File: /var/www/html/application/controllers/Detail.php
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Function: _error_handler
File: /var/www/html/index.php
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Function: require_once
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
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Function: _error_handler
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Function: require_once
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
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Function: _error_handler
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Function: require_once
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Filename: models/Detail_model.php
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Function: strpos
File: /var/www/html/application/controllers/Detail.php
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Function: insertAPISummary
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Function: require_once
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Filename: controllers/Detail.php
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Function: _error_handler
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Function: require_once
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Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
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Function: _error_handler
File: /var/www/html/index.php
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
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Function: _error_handler
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Filename: controllers/Detail.php
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Function: _error_handler
File: /var/www/html/index.php
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Filename: controllers/Detail.php
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Function: _error_handler
File: /var/www/html/index.php
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Filename: controllers/Detail.php
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Function: _error_handler
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Function: _error_handler
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Filename: controllers/Detail.php
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Function: _error_handler
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Message: file_get_contents(https://...@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
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File: /var/www/html/application/helpers/my_audit_helper.php
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Function: file_get_contents
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Function: simplexml_load_file_from_url
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Function: getPubMedXML
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Function: GetPubMedArticleOutput_2016
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Function: pubMedSearch_Global
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Function: pubMedGetRelatedKeyword
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Function: require_once
In vitro screens using cellular preparations expressing human Ether-à-go-go related gene (hERG) potassium channels have become an intrinsic tool for evaluating cardiac liability of compounds during early preclinical stage development. Although hERG channel blocking effects are most reliably evaluated using the low-throughput, manual patch clamp technique, methods and technologies that yield hERG activity data in multiwell format are required to address increased throughput requirements. In most cases, multiwell approaches to measuring hERG activity involve achieving a reasonable balance between throughput and data fidelity. Here we compared two functional multiwell hERG assays: a fluorescence-based fluorometric imaging plate reader (FLIPR(®)) screen measuring thallium (Tl(+)) influx through hERG channels and an automated patch clamp assay using an IonWorks Quattro(®). Mean Z' values for FLIPR-Tl(+) and IonWorks Quattro assays were similar, 0.57 ± 0.09 (±SD; n = 10) versus 0.63 ± 0.11 (n = 12), respectively. IC₅₀ determinations for a set of 17 reference compounds were used to evaluate potency shifts relative to conventional voltage clamp data. The reference compound set included members that are known to exert severe potency shifts in multiwell assays. Mean potency shift values for FLIPR-Tl(+) and IonWorks Quattro assays were 117- and 8-fold, respectively. On the basis of reduced potency shifts and low data variability, we conclude that the IonWorks Quattro screen was a better predictor of hERG activity in conventional whole-cell patch clamp than the Tl(+) influx assay.
Download full-text PDF |
Source |
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http://dx.doi.org/10.1089/adt.2010.0267 | DOI Listing |
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