U.S. flag

An official website of the United States government

Dot gov

The .gov means it's official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you're on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Assessment of the DNA Damaging Potential of Environmental Chemicals Using a Quantitative High-throughput Screening Approach to Measure p53 Activation

Witt KL, Hsieh JH, Smith-Roe SL, Xia M, Huang R, Zhao J, Auerbach SS, Hur J, Tice RR.
Environmental and Molecular Mutagenesis (2017) DOI: https://doi.org/10.1002/em.22112 PMID: 28714573


Publication


Abstract

Genotoxicity potential is a critical component of any comprehensive toxicological profile. Compounds that induce DNA or chromosomal damage often activate p53, a transcription factor essential to cell cycle regulation. Thus, within the US Tox21 Program, we screened a library of ∼10,000 (∼8,300 unique) environmental compounds and drugs for activation of the p53-signaling pathway using a quantitative high-throughput screening assay employing HCT-116 cells (p53+/+ ) containing a stably integrated β-lactamase reporter gene under control of the p53 response element (p53RE). Cells were exposed (-S9) for 16 hr at 15 concentrations (generally 1.2 nM to 92 μM) three times, independently. Excluding compounds that failed analytical chemistry analysis or were suspected of inducing assay interference, 365 (4.7%) of 7,849 unique compounds were concluded to activate p53. As part of an in-depth characterization of our results, we first compared them with results from traditional in vitro genotoxicity assays (bacterial mutation, chromosomal aberration); ∼15% of known, direct-acting genotoxicants in our library activated the p53RE. Mining the Comparative Toxicogenomics Database revealed that these p53 actives were significantly associated with increased expression of p53 downstream genes involved in DNA damage responses. Furthermore, 53 chemical substructures associated with genotoxicity were enriched in certain classes of p53 actives, for example, anthracyclines (antineoplastics) and vinca alkaloids (tubulin disruptors). Interestingly, the tubulin disruptors manifested unusual nonmonotonic concentration response curves suggesting activity through a unique p53 regulatory mechanism. Through the analysis of our results, we aim to define a role for this assay as one component of a comprehensive toxicological characterization of large compound libraries. Environ. Mol. Mutagen. 58:494-507, 2017.

Figures


Figure 1. Distribution of potency and efficacy values.

(a) Distribution of potency and efficacy values for compounds active in the p53RE assay. (b) Distribution of potency and efficacy values for structural fingerprints that are enriched with compounds active in the p53RE assay. POD, point of departure; PPV, positive predictive value.

Figure 2. Association analysis between chemical activity in the p53RE assay.

Association analysis between chemical activity in the p53RE assay and chemical‐induced increased expression of downstream genes in the p53 signaling pathway. Blue text: chemical‐gene data applied in the analysis; pink background: significant association between chemical activity in the p53RE assay and chemical‐induced increased expression of the gene. Plot created by KEGG Mapper, http://www.kegg.jp/kegg/mapper.html.

Figure 3. Association analysis between chemical activity in the p53RE assay and chemical annotations

Association analysis between chemical activity in the p53RE assay and chemical annotations. Terms for chemical annotations are taken directly from the DrugMatrix and DrugBank databases; ATC: WHO drug classification system (ATC) identifiers. For additional descriptions of the categories, please refer to Supporting Information, Methods.

Figure 4. Distribution of the fold change of the EC50 values, and Examples of dose–response curves.

(a) Distribution of the fold change of the EC50 values for the cell viability data and the EC50 values for the p53RE ratio data. Dotted vertical lines indicate 3.2‐fold difference between ratio data and cytotoxicity, where cytotoxicity occurs at higher concentrations (right side) or lower concentrations (left side) than the p53RE response.
(b) Examples of dose–response curves of known (docetaxel) and potential (chromomycin A3) tubulin inhibitors. Purple: ratio data; black: cell viability data. Plots generated by https://ntp.niehs.nih.gov/sandbox/tox21-curve-visualization/.

Tables


Table 1. Protocol for the p53RE qHTS Assay

Table 2. Association analysis.

Association analysis between chemical activity in the p53RE assay and chemical‐induced increased expression of downstream genes in the p53 signaling pathway

Table 3. Comparison of p53RE qHTS Assay Activity Calls and QSAR Model Predictions.

Comparison of p53RE qHTS Assay Activity Calls and QSAR Model Predictions for Bacterial Mutagenicity or Traditional Genotoxicity Assay Results

Supplemental Materials


Supporting Information

SettingsRequest history8.3.17PHP Version1.25sRequest Duration23MBMemory UsageAuth statusGET paper/{id}
status
200 OK
full_url
https://cebs-ext.niehs.nih.gov/cebs/paper/4117
action_name
paper
controller_action
Modules\BinViews\Http\Controllers\PublicationManuscriptController@show
Theme
Open Button Position
Hide Empty Tabs
Autoshow
Reset to defaults
status
200 OK
full_url
https://cebs-ext.niehs.nih.gov/cebs/paper/4117
action_name
paper
controller_action
Modules\BinViews\Http\Controllers\PublicationManuscriptController@show
uri
GET paper/{id}
controller
Modules\BinViews\Http\Controllers\PublicationManuscriptController@show
file
modules/BinViews/Http/Controllers/PublicationManuscriptController.php:70-94
middleware
web
duration
1.27s
peak_memory
28MB
response
text/html; charset=UTF-8
request_format
html
request_query
[]
request_request
[]
request_headers
0 of 0
array:16 [ "x-forwarded-for" => array:1 [ 0 => "3.135.222.93" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate, br, zstd" ] "sec-fetch-dest" => array:1 [ 0 => "document" ] "sec-fetch-user" => array:1 [ 0 => "?1" ] "sec-fetch-mode" => array:1 [ 0 => "navigate" ] "sec-fetch-site" => array:1 [ 0 => "none" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "sec-ch-ua-platform" => array:1 [ 0 => ""Windows"" ] "sec-ch-ua-mobile" => array:1 [ 0 => "?0" ] "sec-ch-ua" => array:1 [ 0 => ""HeadlessChrome";v="129", "Not=A?Brand";v="8", "Chromium";v="129"" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] "connection" => array:1 [ 0 => "keep-alive" ] "host" => array:1 [ 0 => "cebs-ext.niehs.nih.gov" ] ]
request_cookies
[]
response_headers
0 of 0
array:3 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Fri, 04 Apr 2025 05:13:03 GMT" ] ]
session_attributes
0 of 0
array:1 [ "_token" => "t16lH4dpwqPIgNy6UtAuC94RcSTZ3lalYGigb8Ab" ]
  • warninglog[01:13:03] LOG.warning: Creation of dynamic property Vistronix\Saga\Services\PrivateNetworkService::...
  • Booting (571ms)time
  • Application (683ms)time
  • Routing (8.41ms)
  • Preparing Response (477ms)
  • 1 x Application (54.49%)
    683ms
    1 x Booting (45.51%)
    571ms
    1 x Preparing Response (38.07%)
    477ms
    1 x Routing (0.67%)
    8.41ms
    79 templates were rendered
    • 1x binviews::layouts.manuscriptmanuscript.blade.php#?blade
    • 4x ariadne::spools.style-itemstyle-item.blade.php#?blade
    • 4x ariadne::spools.script-itemscript-item.blade.php#?blade
    • 2x ariadne::nav.breadcrumbsbreadcrumbs.blade.php#?blade
    • 1x navnav.blade.php#?blade
    • 1x ariadne::nav.navbarnavbar.blade.php#?blade
    • 1x ariadne::nav.foundation-navfoundation-nav.blade.php#?blade
    • 12x ariadne::spools.linklink.blade.php#?blade
    • 1x ariadne::nav.ariadne-navariadne-nav.blade.php#?blade
    • 1x ariadne::nav.table-of-contentstable-of-contents.blade.php#?blade
    • 4x ariadne::spools.headlineheadline.blade.php#?blade
    • 8x binviews::partials.filesfiles.blade.php#?blade
    • 9x binviews::partials.file_link_itemfile_link_item.blade.php#?blade
    • 1x ariadne::layouts.ariadneariadne.blade.php#?blade
    • 1x ariadne::imports.meta-primarymeta-primary.blade.php#?blade
    • 1x ariadne::imports.metadatametadata.blade.php#?blade
    • 4x ariadne::spools.metadata-itemmetadata-item.blade.php#?blade
    • 1x ariadne::imports.stylesheets-primarystylesheets-primary.blade.php#?blade
    • 1x ariadne::imports.stylesheetsstylesheets.blade.php#?blade
    • 2x ariadne::spools.rellink-itemrellink-item.blade.php#?blade
    • 1x ariadne::imports.headscripts-primaryheadscripts-primary.blade.php#?blade
    • 2x ariadne::imports.scriptlistscriptlist.blade.php#?blade
    • 1x ariadne::content.analyticsanalytics.blade.php#?blade
    • 1x ariadne::access.noscript-supportnoscript-support.blade.php#?blade
    • 1x ariadne::access.skip-navskip-nav.blade.php#?blade
    • 1x ariadne::access.vpn-checkvpn-check.blade.php#?blade
    • 1x ariadne::header.headerheader.blade.php#?blade
    • 1x ariadne::access.javascript-recommended-checkjavascript-recommended-check.blade.php#?blade
    • 1x ariadne::spools.messagemessage.blade.php#?blade
    • 1x ariadne::header.official-govofficial-gov.blade.php#?blade
    • 1x ariadne::header.ntpsharedntpshared.blade.php#?blade
    • 1x ariadne::access.javascript-required-checkjavascript-required-check.blade.php#?blade
    • 1x ariadne::content.messagesmessages.blade.php#?blade
    • 1x ariadne::footer.footerfooter.blade.php#?blade
    • 1x ariadne::footer.ntpsharedntpshared.blade.php#?blade
    • 1x ariadne::footer.closercloser.blade.php#?blade
    • 1x ariadne::access.download-playersdownload-players.blade.php#?blade
    • 1x ariadne::imports.bodyscripts-primarybodyscripts-primary.blade.php#?blade
    uri
    GET paper/{id}
    middleware
    web
    controller
    Modules\BinViews\Http\Controllers\PublicationManuscriptController@show
    as
    paper
    file
    modules/BinViews/Http/Controllers/PublicationManuscriptController.php:70-94
    32 statements were executed (9 duplicates)Show only duplicates114ms
    • PublicationManuscriptController.php#87CEBSBINConnection Established
      Backtrace
      • modules/BinViews/Http/Controllers/PublicationManuscriptController.php:87
      • vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:44
      • vendor/laravel/framework/src/Illuminate/Routing/Route.php:266
      • vendor/laravel/framework/src/Illuminate/Routing/Route.php:212
    • OracleBuilder.php#159CEBSBIN3.82msselect * from (select * from "BIN" where "BIN"."BIN_ID" = 4117 and "IS_DELETED" != 'T' and "BIN_TYPE" = 'Publication' and "REVIEW_STATUS" = 'public') where rownum = 1
      Bindings
      • 0: 4117
      • 1: T
      • 2: Publication
      • 3: public
      Hints
      • Use SELECT * only if you need all columns from table
      • The != operator is not standard. Use the <> operator to test for inequality instead.
      Backtrace
      • vendor/yajra/laravel-oci8/src/Oci8/Query/OracleBuilder.php:159
      • modules/BinViews/Http/Controllers/PublicationManuscriptController.php:87
      • vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:44
      • vendor/laravel/framework/src/Illuminate/Routing/Route.php:266
    • OracleBuilder.php#159CEBSBIN2.61msselect * from "BIN" where "BIN_ID" = 4117
      Bindings
      • 0: 4117
      Hints
      • Use SELECT * only if you need all columns from table
      Backtrace
      • vendor/yajra/laravel-oci8/src/Oci8/Query/OracleBuilder.php:159
      • modules/BinViews/Services/BreadcrumbService.php:32
      • modules/BinViews/Routes/breadcrumbs.php:55
      • vendor/diglactic/laravel-breadcrumbs/src/Generator.php:64
      • vendor/diglactic/laravel-breadcrumbs/src/Generator.php:42
    • OracleBuilder.php#159CEBSBIN7.21msselect * from "BIN_CHARACTERISTICS" where "BIN_CHARACTERISTICS"."BIN_ID" = 4117 and "BIN_CHARACTERISTICS"."BIN_ID" is not null
      Bindings
      • 0: 4117
      Hints
      • Use SELECT * only if you need all columns from table
      Backtrace
      • vendor/yajra/laravel-oci8/src/Oci8/Query/OracleBuilder.php:159
      • modules/BinViews/Models/PublicationManuscript.php:115
      • view::binviews::layouts.manuscript:32
      • vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
    • OracleBuilder.php#159CEBSBIN10.03msselect * from "BIN_LIBRARY" where "BIN_LIBRARY"."BIN_ID" = 4117 and "BIN_LIBRARY"."BIN_ID" is not null and "IS_DELETED" != 'T' order by "LIBRARY_NAME" asc
      Bindings
      • 0: 4117
      • 1: T
      Hints
      • Use SELECT * only if you need all columns from table
      • The != operator is not standard. Use the <> operator to test for inequality instead.
      Backtrace
      • vendor/yajra/laravel-oci8/src/Oci8/Query/OracleBuilder.php:159
      • modules/BinViews/Models/PublicationManuscript.php:67
      • view::binviews::layouts.manuscript:36
      • vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
    • OracleBuilder.php#159CEBSBIN1.56msselect * from (select * from "BIN_LIBRARY_GROUP" where "BIN_LIBRARY_GROUP"."LIBRARY_GROUP_ID" = 19 and "BIN_LIBRARY_GROUP"."LIBRARY_GROUP_ID" is not null) where rownum = 1
      Bindings
      • 0: 19
      Hints
      • Use SELECT * only if you need all columns from table
      Backtrace
      • vendor/yajra/laravel-oci8/src/Oci8/Query/OracleBuilder.php:159
      • modules/BinViews/Models/PublicationManuscript.php:75
      • modules/BinViews/Models/PublicationManuscript.php:71
      • view::binviews::layouts.manuscript:36
      • vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
    • OracleBuilder.php#159CEBSBIN1.46msselect * from (select * from "BIN_LIBRARY_GROUP" where "BIN_LIBRARY_GROUP"."LIBRARY_GROUP_ID" = 20 and "BIN_LIBRARY_GROUP"."LIBRARY_GROUP_ID" is not null) where rownum = 1
      Bindings
      • 0: 20
      Hints
      • Use SELECT * only if you need all columns from table
      Backtrace
      • vendor/yajra/laravel-oci8/src/Oci8/Query/OracleBuilder.php:159
      • modules/BinViews/Models/PublicationManuscript.php:75
      • modules/BinViews/Models/PublicationManuscript.php:71
      • view::binviews::layouts.manuscript:36
      • vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
    • OracleBuilder.php#159CEBSBIN1.41msselect * from (select * from "BIN_LIBRARY_GROUP" where "BIN_LIBRARY_GROUP"."LIBRARY_GROUP_ID" = 20 and "BIN_LIBRARY_GROUP"."LIBRARY_GROUP_ID" is not null) where rownum = 1
      Bindings
      • 0: 20
      Hints
      • Use SELECT * only if you need all columns from table
      Backtrace
      • vendor/yajra/laravel-oci8/src/Oci8/Query/OracleBuilder.php:159
      • modules/BinViews/Models/PublicationManuscript.php:75
      • modules/BinViews/Models/PublicationManuscript.php:71
      • view::binviews::layouts.manuscript:36
      • vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
    • OracleBuilder.php#159CEBSBIN1.33msselect * from (select * from "BIN_LIBRARY_GROUP" where "BIN_LIBRARY_GROUP"."LIBRARY_GROUP_ID" = 20 and "BIN_LIBRARY_GROUP"."LIBRARY_GROUP_ID" is not null) where rownum = 1
      Bindings
      • 0: 20
      Hints
      • Use SELECT * only if you need all columns from table
      Backtrace
      • vendor/yajra/laravel-oci8/src/Oci8/Query/OracleBuilder.php:159
      • modules/BinViews/Models/PublicationManuscript.php:75
      • modules/BinViews/Models/PublicationManuscript.php:71
      • view::binviews::layouts.manuscript:36
      • vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
    • OracleBuilder.php#159CEBSBIN1.55msselect * from (select * from "BIN_LIBRARY_GROUP" where "BIN_LIBRARY_GROUP"."LIBRARY_GROUP_ID" = 20 and "BIN_LIBRARY_GROUP"."LIBRARY_GROUP_ID" is not null) where rownum = 1
      Bindings
      • 0: 20
      Hints
      • Use SELECT * only if you need all columns from table
      Backtrace
      • vendor/yajra/laravel-oci8/src/Oci8/Query/OracleBuilder.php:159
      • modules/BinViews/Models/PublicationManuscript.php:75
      • modules/BinViews/Models/PublicationManuscript.php:71
      • view::binviews::layouts.manuscript:36
      • vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
    • OracleBuilder.php#159CEBSBIN1.32msselect * from (select * from "BIN_LIBRARY_GROUP" where "BIN_LIBRARY_GROUP"."LIBRARY_GROUP_ID" = 23 and "BIN_LIBRARY_GROUP"."LIBRARY_GROUP_ID" is not null) where rownum = 1
      Bindings
      • 0: 23
      Hints
      • Use SELECT * only if you need all columns from table
      Backtrace
      • vendor/yajra/laravel-oci8/src/Oci8/Query/OracleBuilder.php:159
      • modules/BinViews/Models/PublicationManuscript.php:75
      • modules/BinViews/Models/PublicationManuscript.php:71
      • view::binviews::layouts.manuscript:36
      • vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
    • OracleBuilder.php#159CEBSBIN1.42msselect * from (select * from "BIN_LIBRARY_GROUP" where "BIN_LIBRARY_GROUP"."LIBRARY_GROUP_ID" = 21 and "BIN_LIBRARY_GROUP"."LIBRARY_GROUP_ID" is not null) where rownum = 1
      Bindings
      • 0: 21
      Hints
      • Use SELECT * only if you need all columns from table
      Backtrace
      • vendor/yajra/laravel-oci8/src/Oci8/Query/OracleBuilder.php:159
      • modules/BinViews/Models/PublicationManuscript.php:75
      • modules/BinViews/Models/PublicationManuscript.php:71
      • view::binviews::layouts.manuscript:36
      • vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
    • OracleBuilder.php#159CEBSBIN2.21msselect * from (select * from "BIN_LIBRARY_GROUP" where "BIN_LIBRARY_GROUP"."LIBRARY_GROUP_ID" = 21 and "BIN_LIBRARY_GROUP"."LIBRARY_GROUP_ID" is not null) where rownum = 1
      Bindings
      • 0: 21
      Hints
      • Use SELECT * only if you need all columns from table
      Backtrace
      • vendor/yajra/laravel-oci8/src/Oci8/Query/OracleBuilder.php:159
      • modules/BinViews/Models/PublicationManuscript.php:75
      • modules/BinViews/Models/PublicationManuscript.php:71
      • view::binviews::layouts.manuscript:36
      • vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
    • OracleBuilder.php#159CEBSBIN1.34msselect * from (select * from "BIN_LIBRARY_GROUP" where "BIN_LIBRARY_GROUP"."LIBRARY_GROUP_ID" = 21 and "BIN_LIBRARY_GROUP"."LIBRARY_GROUP_ID" is not null) where rownum = 1
      Bindings
      • 0: 21
      Hints
      • Use SELECT * only if you need all columns from table
      Backtrace
      • vendor/yajra/laravel-oci8/src/Oci8/Query/OracleBuilder.php:159
      • modules/BinViews/Models/PublicationManuscript.php:75
      • modules/BinViews/Models/PublicationManuscript.php:71
      • view::binviews::layouts.manuscript:36
      • vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
    • OracleBuilder.php#159CEBSBIN6.29msselect "BIN_FILE".*, "BIN_LIBRARY_FILES"."LIBRARY_ID" as "LARAVEL_THROUGH_KEY" from "BIN_FILE" inner join "BIN_LIBRARY_FILES" on "BIN_LIBRARY_FILES"."FILE_ID" = "BIN_FILE"."FILE_ID" where "BIN_LIBRARY_FILES"."LIBRARY_ID" = 8603 and "IS_DELETED" != 'T'
      Bindings
      • 0: 8603
      • 1: T
      Hints
      • The != operator is not standard. Use the <> operator to test for inequality instead.
      Backtrace
      • vendor/yajra/laravel-oci8/src/Oci8/Query/OracleBuilder.php:159
      • view::binviews::layouts.manuscript:52
      • vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:75
    • OracleBuilder.php#159CEBSBIN3.93msselect "BIN_FILE".*, "BIN_LIBRARY_FILES"."LIBRARY_ID" as "LARAVEL_THROUGH_KEY" from "BIN_FILE" inner join "BIN_LIBRARY_FILES" on "BIN_LIBRARY_FILES"."FILE_ID" = "BIN_FILE"."FILE_ID" where "BIN_LIBRARY_FILES"."LIBRARY_ID" = 8864 and "IS_DELETED" != 'T'
      Bindings
      • 0: 8864
      • 1: T
      Hints
      • The != operator is not standard. Use the <> operator to test for inequality instead.
      Backtrace
      • vendor/yajra/laravel-oci8/src/Oci8/Query/OracleBuilder.php:159
      • view::binviews::layouts.manuscript:52
      • vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:75
    • OracleBuilder.php#159CEBSBIN16.2msselect * from "BIN_REVIEW" where "BIN_REVIEW"."FILE_ID" = '1de240ff62ed87f901631cd938e5012f' and "BIN_REVIEW"."FILE_ID" is not null
      Bindings
      • 0: 1de240ff62ed87f901631cd938e5012f
      Hints
      • Use SELECT * only if you need all columns from table
      Backtrace
      • vendor/yajra/laravel-oci8/src/Oci8/Query/OracleBuilder.php:159
      • modules/BinViews/Models/File.php:63
      • modules/BinViews/Models/Library.php:65
      • modules/BinViews/Models/Library.php:64
      • view::binviews::layouts.manuscript:54
    • OracleBuilder.php#159CEBSBIN3.12msselect "BIN_FILE".*, "BIN_LIBRARY_FILES"."LIBRARY_ID" as "LARAVEL_THROUGH_KEY" from "BIN_FILE" inner join "BIN_LIBRARY_FILES" on "BIN_LIBRARY_FILES"."FILE_ID" = "BIN_FILE"."FILE_ID" where "BIN_LIBRARY_FILES"."LIBRARY_ID" = 8865 and "IS_DELETED" != 'T'
      Bindings
      • 0: 8865
      • 1: T
      Hints
      • The != operator is not standard. Use the <> operator to test for inequality instead.
      Backtrace
      • vendor/yajra/laravel-oci8/src/Oci8/Query/OracleBuilder.php:159
      • view::binviews::layouts.manuscript:52
      • vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:75
    • OracleBuilder.php#159CEBSBIN4.93msselect * from "BIN_REVIEW" where "BIN_REVIEW"."FILE_ID" = '1de240ff62ed87f901631cd9a20f0130' and "BIN_REVIEW"."FILE_ID" is not null
      Bindings
      • 0: 1de240ff62ed87f901631cd9a20f0130
      Hints
      • Use SELECT * only if you need all columns from table
      Backtrace
      • vendor/yajra/laravel-oci8/src/Oci8/Query/OracleBuilder.php:159
      • modules/BinViews/Models/File.php:63
      • modules/BinViews/Models/Library.php:65
      • modules/BinViews/Models/Library.php:64
      • view::binviews::layouts.manuscript:54
    • OracleBuilder.php#159CEBSBIN2.35msselect "BIN_FILE".*, "BIN_LIBRARY_FILES"."LIBRARY_ID" as "LARAVEL_THROUGH_KEY" from "BIN_FILE" inner join "BIN_LIBRARY_FILES" on "BIN_LIBRARY_FILES"."FILE_ID" = "BIN_FILE"."FILE_ID" where "BIN_LIBRARY_FILES"."LIBRARY_ID" = 8867 and "IS_DELETED" != 'T'
      Bindings
      • 0: 8867
      • 1: T
      Hints
      • The != operator is not standard. Use the <> operator to test for inequality instead.
      Backtrace
      • vendor/yajra/laravel-oci8/src/Oci8/Query/OracleBuilder.php:159
      • view::binviews::layouts.manuscript:52
      • vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:75
    • OracleBuilder.php#159CEBSBIN3.88msselect * from "BIN_REVIEW" where "BIN_REVIEW"."FILE_ID" = '1de240ff62ed87f901631cd9ee5a0131' and "BIN_REVIEW"."FILE_ID" is not null
      Bindings
      • 0: 1de240ff62ed87f901631cd9ee5a0131
      Hints
      • Use SELECT * only if you need all columns from table
      Backtrace
      • vendor/yajra/laravel-oci8/src/Oci8/Query/OracleBuilder.php:159
      • modules/BinViews/Models/File.php:63
      • modules/BinViews/Models/Library.php:65
      • modules/BinViews/Models/Library.php:64
      • view::binviews::layouts.manuscript:54
    • OracleBuilder.php#159CEBSBIN2.45msselect "BIN_FILE".*, "BIN_LIBRARY_FILES"."LIBRARY_ID" as "LARAVEL_THROUGH_KEY" from "BIN_FILE" inner join "BIN_LIBRARY_FILES" on "BIN_LIBRARY_FILES"."FILE_ID" = "BIN_FILE"."FILE_ID" where "BIN_LIBRARY_FILES"."LIBRARY_ID" = 8869 and "IS_DELETED" != 'T'
      Bindings
      • 0: 8869
      • 1: T
      Hints
      • The != operator is not standard. Use the <> operator to test for inequality instead.
      Backtrace
      • vendor/yajra/laravel-oci8/src/Oci8/Query/OracleBuilder.php:159
      • view::binviews::layouts.manuscript:52
      • vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:75
    • OracleBuilder.php#159CEBSBIN3.49msselect * from "BIN_REVIEW" where "BIN_REVIEW"."FILE_ID" = '1de240ff62ed87f901631cda30a30132' and "BIN_REVIEW"."FILE_ID" is not null
      Bindings
      • 0: 1de240ff62ed87f901631cda30a30132
      Hints
      • Use SELECT * only if you need all columns from table
      Backtrace
      • vendor/yajra/laravel-oci8/src/Oci8/Query/OracleBuilder.php:159
      • modules/BinViews/Models/File.php:63
      • modules/BinViews/Models/Library.php:65
      • modules/BinViews/Models/Library.php:64
      • view::binviews::layouts.manuscript:54
    • OracleBuilder.php#159CEBSBIN2.47msselect "BIN_FILE".*, "BIN_LIBRARY_FILES"."LIBRARY_ID" as "LARAVEL_THROUGH_KEY" from "BIN_FILE" inner join "BIN_LIBRARY_FILES" on "BIN_LIBRARY_FILES"."FILE_ID" = "BIN_FILE"."FILE_ID" where "BIN_LIBRARY_FILES"."LIBRARY_ID" = 8863 and "IS_DELETED" != 'T'
      Bindings
      • 0: 8863
      • 1: T
      Hints
      • The != operator is not standard. Use the <> operator to test for inequality instead.
      Backtrace
      • vendor/yajra/laravel-oci8/src/Oci8/Query/OracleBuilder.php:159
      • view::binviews::layouts.manuscript:52
      • vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:75
    • OracleBuilder.php#159CEBSBIN4.19msselect * from "BIN_REVIEW" where "BIN_REVIEW"."FILE_ID" = '1de240ff62ed87f901631cda98270133' and "BIN_REVIEW"."FILE_ID" is not null
      Bindings
      • 0: 1de240ff62ed87f901631cda98270133
      Hints
      • Use SELECT * only if you need all columns from table
      Backtrace
      • vendor/yajra/laravel-oci8/src/Oci8/Query/OracleBuilder.php:159
      • modules/BinViews/Models/File.php:63
      • modules/BinViews/Models/Library.php:65
      • modules/BinViews/Models/Library.php:64
      • view::binviews::layouts.manuscript:54
    • OracleBuilder.php#159CEBSBIN2.31msselect "BIN_FILE".*, "BIN_LIBRARY_FILES"."LIBRARY_ID" as "LARAVEL_THROUGH_KEY" from "BIN_FILE" inner join "BIN_LIBRARY_FILES" on "BIN_LIBRARY_FILES"."FILE_ID" = "BIN_FILE"."FILE_ID" where "BIN_LIBRARY_FILES"."LIBRARY_ID" = 8866 and "IS_DELETED" != 'T'
      Bindings
      • 0: 8866
      • 1: T
      Hints
      • The != operator is not standard. Use the <> operator to test for inequality instead.
      Backtrace
      • vendor/yajra/laravel-oci8/src/Oci8/Query/OracleBuilder.php:159
      • view::binviews::layouts.manuscript:52
      • vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:75
    • OracleBuilder.php#159CEBSBIN3.4msselect * from "BIN_REVIEW" where "BIN_REVIEW"."FILE_ID" = '1de240ff62ed87f901631cdb454a0134' and "BIN_REVIEW"."FILE_ID" is not null
      Bindings
      • 0: 1de240ff62ed87f901631cdb454a0134
      Hints
      • Use SELECT * only if you need all columns from table
      Backtrace
      • vendor/yajra/laravel-oci8/src/Oci8/Query/OracleBuilder.php:159
      • modules/BinViews/Models/File.php:63
      • modules/BinViews/Models/Library.php:65
      • modules/BinViews/Models/Library.php:64
      • view::binviews::layouts.manuscript:54
    • OracleBuilder.php#159CEBSBIN2.34msselect "BIN_FILE".*, "BIN_LIBRARY_FILES"."LIBRARY_ID" as "LARAVEL_THROUGH_KEY" from "BIN_FILE" inner join "BIN_LIBRARY_FILES" on "BIN_LIBRARY_FILES"."FILE_ID" = "BIN_FILE"."FILE_ID" where "BIN_LIBRARY_FILES"."LIBRARY_ID" = 8868 and "IS_DELETED" != 'T'
      Bindings
      • 0: 8868
      • 1: T
      Hints
      • The != operator is not standard. Use the <> operator to test for inequality instead.
      Backtrace
      • vendor/yajra/laravel-oci8/src/Oci8/Query/OracleBuilder.php:159
      • view::binviews::layouts.manuscript:52
      • vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:75
    • OracleBuilder.php#159CEBSBIN3.39msselect * from "BIN_REVIEW" where "BIN_REVIEW"."FILE_ID" = '1de240ff62ed87f901631cdb94df0135' and "BIN_REVIEW"."FILE_ID" is not null
      Bindings
      • 0: 1de240ff62ed87f901631cdb94df0135
      Hints
      • Use SELECT * only if you need all columns from table
      Backtrace
      • vendor/yajra/laravel-oci8/src/Oci8/Query/OracleBuilder.php:159
      • modules/BinViews/Models/File.php:63
      • modules/BinViews/Models/Library.php:65
      • modules/BinViews/Models/Library.php:64
      • view::binviews::layouts.manuscript:54
    • OracleBuilder.php#159CEBSBIN2.77msselect "BIN_FILE".*, "BIN_LIBRARY_FILES"."LIBRARY_ID" as "LARAVEL_THROUGH_KEY" from "BIN_FILE" inner join "BIN_LIBRARY_FILES" on "BIN_LIBRARY_FILES"."FILE_ID" = "BIN_FILE"."FILE_ID" where "BIN_LIBRARY_FILES"."LIBRARY_ID" = 8870 and "IS_DELETED" != 'T'
      Bindings
      • 0: 8870
      • 1: T
      Hints
      • The != operator is not standard. Use the <> operator to test for inequality instead.
      Backtrace
      • vendor/yajra/laravel-oci8/src/Oci8/Query/OracleBuilder.php:159
      • view::binviews::layouts.manuscript:52
      • vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:75
    • OracleBuilder.php#159CEBSBIN3.58msselect * from "BIN_REVIEW" where "BIN_REVIEW"."FILE_ID" = '1de240ff62ed87f901636f5b8486040d' and "BIN_REVIEW"."FILE_ID" is not null
      Bindings
      • 0: 1de240ff62ed87f901636f5b8486040d
      Hints
      • Use SELECT * only if you need all columns from table
      Backtrace
      • vendor/yajra/laravel-oci8/src/Oci8/Query/OracleBuilder.php:159
      • modules/BinViews/Models/File.php:63
      • modules/BinViews/Models/Library.php:65
      • modules/BinViews/Models/Library.php:64
      • view::binviews::layouts.manuscript:54
    • OracleBuilder.php#159CEBSBIN3.33msselect * from "BIN_REVIEW" where "BIN_REVIEW"."FILE_ID" = '1de240ff62ed87f901636f5b84be040e' and "BIN_REVIEW"."FILE_ID" is not null
      Bindings
      • 0: 1de240ff62ed87f901636f5b84be040e
      Hints
      • Use SELECT * only if you need all columns from table
      Backtrace
      • vendor/yajra/laravel-oci8/src/Oci8/Query/OracleBuilder.php:159
      • modules/BinViews/Models/File.php:63
      • modules/BinViews/Models/Library.php:65
      • modules/BinViews/Models/Library.php:64
      • view::binviews::layouts.manuscript:54
    • OracleBuilder.php#159CEBSBIN1.89msselect * from "BIN" where "BIN_ID" = 4117
      Bindings
      • 0: 4117
      Hints
      • Use SELECT * only if you need all columns from table
      Backtrace
      • vendor/yajra/laravel-oci8/src/Oci8/Query/OracleBuilder.php:159
      • modules/BinViews/Services/BreadcrumbService.php:32
      • modules/BinViews/Routes/breadcrumbs.php:55
      • vendor/diglactic/laravel-breadcrumbs/src/Generator.php:64
      • vendor/diglactic/laravel-breadcrumbs/src/Generator.php:42
    Modules\BinViews\Models\Library
    9Library.php#?
    Modules\BinViews\Models\LibraryGroup
    9LibraryGroup.php#?
    Modules\BinViews\Models\File
    9File.php#?
    Modules\BinViews\Models\Review
    9Review.php#?
    Modules\BinViews\Models\Characteristic
    5Characteristic.php#?
    Modules\BinViews\Models\PublicationManuscript
    3PublicationManuscript.php#?
      web
      null
        _token
        t16lH4dpwqPIgNy6UtAuC94RcSTZ3lalYGigb8Ab
        ClearShow all
        Date ↕MethodURLData
        #12025-04-04 01:13:04GET/cebs/paper/41171793244