Generic placeholder image

Current Protein & Peptide Science

Editor-in-Chief

ISSN (Print): 1389-2037
ISSN (Online): 1875-5550

Review Article

Mixed Mode Chromatography, Complex Development for Large Opportunities

Author(s): Charlotte Cabanne* and Xavier Santarelli

Volume 20, Issue 1, 2019

Page: [22 - 27] Pages: 6

DOI: 10.2174/1389203718666171030104211

Price: $65

Abstract

Mixed mode chromatography resins with salt tolerance, large design space and orthogonal selectivity requires a slightly more complex development than traditional resins. It is important to screen several ligands and several binding and elution conditions. This allows taking full advantage of these resins. High-Throughput Screening (HTS) for Process Development should be done with the help of Design of Experiment (DoE). It could be performed in filter plates or Robocolumns, and assisted by liquid handling automated workstation. Modeling of the results allows the choice of optimal parameters that can then be validated and scaled up. All this leads to a better knowledge and robustness of the purification step.

Keywords: Mixed mode chromatography, high throughput process development, design of experiment, large opportunities, High-Throughput Screening (HTS), Design of Experiment (DoE).

Graphical Abstract

[1]
Yon, R.J. Chromatography of lipophilic proteins on adsorbents containing mixed hydrophobic and ionic groups. Biochem. J., 1972, 126, 765-767.
[2]
Er-El, Z.; Zaidenzaig, Y.; Shaltiel, S. Hydrocarbon-coated Sepharoses. Use in the purification of glycogen phosphorylase. Biochem. Biophys. Res. Commun., 1972, 49(2), 383-390.
[3]
Hofstee, B.H.J. Protein binding by agarose carrying hydrophobic groups in conjunction with charges. Biochem. Biophys. Res. Commun., 1973, 50(3), 751-757.
[4]
Porath, J.; Aspberg, K.; Drevin, H.; Axén, R. Preparation of cyanogen bromide-activated agarose gels. J. Chromatogr. A, 1973, 86, 53-56.
[5]
Hjertén, S.; Rosengren, J.; Pahlman, S. Hydrophobic interaction chromatography: The synthesis and the use of some alkyl and aryl derivatives of agarose. J. Chromatogr. A, 1974, 101, 281-288.
[6]
Shaltiel, S.; Er-El, Z. Hydrophobic chromatography: use for purification of glycogen synthetase. Proc. Natl. Acad. Sci. USA, 1973, 70(3), 778-781.
[7]
Hofstee, B.H.J.; Otillio, N.F. Non-ionic adsorption chromatography of proteins. J. Chromatogr. A, 1978, 159(1), 57-69.
[8]
Sasaki, I.; Gotoh, H.; Yamamoto, R.; Hasegawa, H.; Yamashita, J.; Horio, T. Hydrophobic-ionic chromatography. Its application to purification of porcine pancreas enzymes. J. Biochem., 1979, 86(5), 1537-1548.
[9]
Sasaki, I.; Gotoh, H.; Yamamoto, R.; Tanaka, H.; Takami, K.; Yamashita, K.; Yamashita, J.; Horio, T. Hydrophobic-ionic chromatography: its application to microbial glucose oxidase, hyaluronidase, cholesterol oxidase, and cholesterol esterase. J. Biochem., 1982, 91(5), 1555-1561.
[10]
Kennedy, L.A.; Kopaciewicz, W.; Regnier, F.E. Multimodal liquid chromatography columns for the separation of proteins in either the anion-exchange or hydrophobic- interaction mode. J. Chromatogr. A, 1986, 359, 73-84.
[11]
Bischoff, R.; McLaughlin, L.W. Nucleic acid resolution by mixed-mode chromatography. J. Chromatogr. A, 1984, 296, 329-337.
[12]
Burton, S.C.; Harding, D.R.K. Hydrophobic charge induction chromatography: salt independent protein adsorption and facile elution with aqueous buffers. J. Chromatogr. A, 1998, 814(1-2), 71-81.
[13]
Guerrier, L.; Girot, P.; Schwartz, W.; Boschetti, E. New method for the selective capture of antibodies under physiolgical conditions. Bioseparation, 2000, 9, 211-221.
[14]
Boschetti, E. Antibody separation by hydrophobic charge induction chromatography. Trends Biotechnol., 2002, 20(8), 333-337.
[15]
Arakawa, T.; Kita, Y.; Sato, H.; Ejima, D. MEP chromatography of antibody and Fc-fusion protein using aqueous arginine solution. Protein Expr. Purif., 2009, 63(2), 158-163.
[16]
Xia, H.F.; Lin, D.Q.; Wang, L.P.; Chen, Z.J.; Yao, S.J. Preparation and evaluation of cellulose adsorbents for hydrophobic charge induction chromatography. Ind. Eng. Chem. Res., 2008, 47, 9566-9572.
[17]
Zhao, G.; Peng, G.; Li, F.; Shi, Q.; Sun, Y. 5-Aminoindole, a new ligand for hydrophobic charge induction chromatography. J. Chromatogr. A, 2008, 1211, 90-98.
[18]
Shi, Q.H.; Shen, F.F.; Sun, S. Studies of lysozyme binding to histamine as a ligand for hydrophobic charge induction chromatography. Biotechnol. Prog., 2010, 26, 134-141.
[19]
Zhao, G.; Dong, X.Y.; Sun, Y. Ligands for mixed-mode protein chromatography: Principles, characteristics and design. J. Biotechnol., 2009, 144(1), 3-11.
[20]
Brenac Brochier, V.; Schapman, A.; Santambien, P.; Britsch, L. Fast purification process optimization using mixed-mode chromatography sorbents in pre-packed mini-columns. J. Chromatogr. A, 2008, 1177(2), 226-233.
[21]
Johansson, B.L.; Belew, M.; Eriksson, S.; Glad, G.; Lind, O.; Maloisel, J.L.; Norrman, N. Preparation and characterization of prototypes for multi-modal separation aimed for capture of positively charged biomolecules at high-salt conditions. J. Chromatogr. A, 2003, 1016(1), 35-49.
[22]
Johansson, B.L.; Belew, M.; Eriksson, S.; Glad, G.; Lind, O.; Maloisel, J.L.; Norrman, N. Preparation and characterization of prototypes for multi-modal separation media aimed for capture of negatively charged biomolecules at high salt conditions. J. Chromatogr. A, 2003, 1016(1), 21-33.
[23]
Woo, J.A.; Chen, H.; Snyder, M.A.; Chai, Y.; Frost, R.G.; Cramer, S.M. Defining the property space for chromatographic ligands from a homologous series of mixed-mode ligands. J. Chromatogr. A, 2015, 1407, 58-68.
[24]
Yoshimoto, N.; Minakuchi, K.; Itoh, D.; Isakari, Y.; Yamamoto, S. High-throughput process development methods for chromatography and precipitation of proteins: Advantages and precautions. Eng. Life Sci., 2013, 13(5), 446-455.
[25]
Cabanne, C.; Santarelli, X. Media selection in ion-exchange chromatography in a single microplate. Methods Mol. Biol., 2014, 1129, 45-51.
[26]
Kramarczyk, J.F. High-throughput screening of chromatographic resins and excipients for optimizing selectivity. Master Thesis, Tufts University. 2003.
[27]
Bergander, T.; Nilsson-Välimaa, K.; Öberg, K.; Lacki, K.M. High-throughput process development: determination of dynamic binding capacity using microtiter filter plates filled with chromatography resin. Biotechnol. Prog., 2008, 24(3), 632-639.
[28]
Charlton, H.; Galarza, B.; Beacon, B.; LeRiche, K.; Jones, R. Chromatography process development using 96-well microplate formats. BioPharm Int., 2006, 19, 20-27.
[29]
Baumann, P.; Baumgartner, K.; Hubbuch, J. Influence of binding pH and protein solubility on the dynamic binding capacity in hydrophobic interaction chromatography. J. Chromatogr. A, 2015, 1396, 77-85.
[30]
Bensch, M.; Schulze Wierling, P.; von Lieres, E.; Hubbuch, J. High throughput screening of chromatographic phases for rapid process development. Chem. Eng. Technol., 2005, 28, 1274-1284.
[31]
Rege, K.; Pepsin, M.; Falcon, B.; Steele, L.; Heng, M. High-throughput process development for recombinant protein purification. Biotechnol. Bioeng., 2006, 93, 618-630.
[32]
Thiemann, J.; Jankowski, J.; Rykl, J.; Kurzawski, S.; Pohl, T.; Wittmann-Lievold, B.; Schluter, H. Principle and applications of the protein-purification-parameter screening system. J. Chromatogr. A, 2004, 1043, 73-80.
[33]
Toueille, M.; Uzel, A.; Depoisier, J.F.; Gantier, R. Designing new monoclonal antibody purification processes using mixed-mode chromatography sorbents. J. Chromatogr. B., 2011, 879(13-14), 836-843.
[34]
Pezzini, J.; Joucla, G.; Gantier, R.; Toueille, M.; Lomenech, A.M.; Le Sénéchal, C.; Garbay, B.; Santarelli, X.; Cabanne, C. Antibody capture by mixed-mode chromatography: A comprehensive study from determination of optimal purification conditions to identification of contaminating host cell proteins. J. Chromatogr. A, 2011, 1218, 8197-8208.
[35]
Nfor, B.K.; Noverraz, M.; Chilamkurthi, S.; Verhaert, P.D.; van der Wielen, L.A.; Ottens, M. High-throughput isotherm determination and thermodynamic modeling of protein adsorption on mixed mode adsorbents. J. Chromatogr. A, 2010, 1217(44), 6829-6850.
[36]
Bhambure, R.; Gupta, D.; Rathore, A.S. A novel multimodal chromatography based single step purification process for efficient manufacturing of an E. coli based biotherapeutic protein product. J. Chromatogr. A, 2013, 1314, 188-198.
[37]
Sejergaard, L.; Karkov, H.S.; Krarup, J.K.; Hagel, A.B.; Cramer, S.M. Model-based process development for the purification of a modified human growth hormone using multimodal chromatography. Biotechnol. Prog., 2014, 30(5), 1057-1064.
[38]
Atkinson, A.C.; Tobias, R.D. Optimal experimental design in chromatography. J. Chromatogr. A, 2008, 1177(1), 1-11.
[39]
Lacki, K.M. High-throughput process development of chromatography steps: advantages and limitations of different formats used. Biotechnol. J., 2012, 7(10), 1192-1202.

Rights & Permissions Print Cite
© 2025 Bentham Science Publishers | Privacy Policy
Request history8.2.27PHP Version295msRequest Duration28MBMemory UsageGET article/{article_id}/{param?}Route
  • warninglog[05:10:47] LOG.warning: Optional parameter $article_id declared before required parameter $request i...
  • warninglog[05:10:48] LOG.warning: trim(): Passing null to parameter #1 ($string) of type string is deprecated ...
  • warninglog[05:10:48] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • Booting (91.87ms)time
  • Application (204ms)time
  • 1 x Application (68.9%)
    204ms
    1 x Booting (31.1%)
    91.87ms
    14 templates were rendered
    • articlearticle.blade.php#?blade
    • includes.article_top_bannerarticle_top_banner.blade.php#?blade
    • includes.article_referencearticle_reference.blade.php#?blade
    • export_citation_formexport_citation_form.blade.php#?blade
    • includes.article_bottom_bannerarticle_bottom_banner.blade.php#?blade
    • includes.inc_related_journalsinc_related_journals.blade.php#?blade
    • includes.inc_related_ebooksinc_related_ebooks.blade.php#?blade
    • includes.journal_rightmenujournal_rightmenu.blade.php#?blade
    • includes.journal_right_bannerjournal_right_banner.blade.php#?blade
    • layouts.appapp.blade.php#?blade
    • layouts._login_access_login_access.blade.php#?blade
    • layouts._header_header.blade.php#?blade
    • layouts._main_menu_main_menu.blade.php#?blade
    • layouts._footer_menu_footer_menu.blade.php#?blade
    uri
    GET article/{article_id}/{param?}
    middleware
    web, check_user_access
    controller
    App\Http\Controllers\ArticleController@GetArticleDetails
    namespace
    App\Http\Controllers
    where
    as
    article
    file
    app/Http/Controllers/ArticleController.php:1974-2510
    36 statements were executed, 4 of which were duplicates, 32 unique. Show only duplicated114ms
    • Connection Establishedalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 9. middleware::check_user_access:24
      • 10. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 11. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address (ip_address,visitor_agent,visitor_count, created_on,updated_on) VALUES ('51631602','',1,1740460247,1740460247) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1740460247
      1.23msalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 11. middleware::check_user_access:24
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address_detail (ip_address,visitor_url,visitor_count, created_on,updated_on) VALUES ('51631602','/article/86573',1,1740460247,1740460247)
      210μsalphaeurekaselec_live_10_06_2022UserAccessCheck.php#27
      Backtrace
      • 11. middleware::check_user_access:27
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_trail WHERE to_ip >= 51631602 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51631602) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_corporate WHERE to_ip >= 51631602 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51631602) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_token WHERE to_ip >= 51631602 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51631602) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_trail WHERE to_ip >= 51631602 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51631602) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_corporate WHERE to_ip >= 51631602 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51631602) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_token WHERE to_ip >= 51631602 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51631602) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 51631602 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51631602) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 51631602 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51631602) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 51631602 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51631602) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 51631602 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51631602) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 51631602 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51631602) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 51631602 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51631602) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 51631602 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51631602) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 51631602 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51631602) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 51631602 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51631602) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 51631602 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51631602) limit 1
      11.01msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 51631602
      • 1: 51631602
      • 2: 51631602
      • 3: 51631602
      • 4: 51631602
      • 5: 51631602
      • 6: 51631602
      • 7: 51631602
      • 8: 51631602
      • 9: 51631602
      • 10: 51631602
      • 11: 51631602
      • 12: 51631602
      • 13: 51631602
      • 14: 51631602
      • 15: 51631602
      Backtrace
      • 14. app/Models/UserAccess/UserAccess.php:784
      • 15. middleware::check_user_access:114
      • 16. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 18. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
    • SELECT at.type_name, p.copyright, p.publisher_location,m.month,y.year, a.publish_on, a.nid article_nid,a.article_id, a.pmid, a.issue_id, a.title, a.abstract,a.podcast,a.altmetric_score,a.altmetric_url,a.kudos_url, a.page_count, a.first_page, a.elocator, a.last_page, i.publication_date, a.file_name, a.file_path, a.doi, a.is_epub,a.epub_type, a.volume_id, a.is_uploaded, a.editor_choice, a.is_epub, j.image_file_name, a.article_no, a.art_type AS article_type, a.supplementary_filename,a.html_filename,a.prc_filename,a.epub_filename, a.graph_abs_lg_filename, a.graph_abs_sm_filename, a.oa_image_lg_filename, a.oa_image_sm_filename, j.journal_banner,a.animated_abstract,a.erratum_in,a.erratum_for, (CASE WHEN a.issue_id =0 THEN j.epub_price ELSE j.price END) AS sell_price, j.epub_price, j.nid AS jour_nid, j.title AS journal_title, j.issn, j.eissn,j.journal_id, j.subtitle AS jour_subtitle, v.volume_id,v.volume_name AS volume, v.year_id, i.title AS issue, i.month_id ,i.type issue_type, j.subtitle,j.formerly_title, ac.subtitle AS epub_title,a.crossmark_enabled,a.text_mining_urls,a.license_urls,a.created, a.receivedate, a.revisedate, a.acceptdate,js.js_title FROM article a LEFT JOIN article_section ac ON a.is_epub = ac.art_sec_id LEFT JOIN journal_section js ON a.js_id = js.js_id LEFT JOIN article_type at ON a.art_type = at.art_type_id LEFT JOIN issue i ON a.issue_id = i.issue_id LEFT JOIN month m ON m.id = i.month_id LEFT JOIN volume v ON v.volume_id = a.volume_id INNER JOIN year y ON y.id = v.year_id INNER JOIN journal j ON j.journal_id = a.journal_id INNER JOIN publisher p ON p.publisher_id = j.publisher_id WHERE a.article_id=86573
      760μsalphaeurekaselec_live_10_06_2022Article.php#408
      Backtrace
      • 11. app/Models/Article.php:408
      • 12. app/Http/Controllers/ArticleController.php:2515
      • 13. app/Http/Controllers/ArticleController.php:2035
      • 14. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 15. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `journal` where `journal_id` = 42 limit 1
      1.23msalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 42
      Backtrace
      • 14. app/Models/Journal.php:64
      • 15. app/Http/Controllers/ArticleController.php:2516
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=42) and sj.journal_id!=42 group by `j`.`nid`) as `aggregate_table`
      1.2msalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 16. app/Models/Subject.php:200
      • 17. app/Http/Controllers/ArticleController.php:2517
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=42) and sj.journal_id!=42 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      1.04msalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 14. app/Models/Subject.php:200
      • 15. app/Http/Controllers/ArticleController.php:2517
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=42) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      4msalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 16. app/Models/Subject.php:220
      • 17. app/Http/Controllers/ArticleController.php:2518
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=42) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      3.4msalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 14. app/Models/Subject.php:220
      • 15. app/Http/Controllers/ArticleController.php:2518
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `keywords` where `article_id` = '86573'
      940μsalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 86573
      Backtrace
      • 13. app/Models/Keywords.php:43
      • 14. app/Http/Controllers/ArticleController.php:2519
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `article_citation` where `article_id` = '86573'
      2.39msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 86573
      Backtrace
      • 13. app/Models/Article.php:1570
      • 14. app/Http/Controllers/ArticleController.php:2520
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select CONCAT_WS(' ',au.first_name, ' ', ifnull(au.initials,''), ' ', au.last_name) as authors, CONCAT(au.last_name, IFNULL(CONCAT(' ', au.initials), ''), ' ', au.first_name) AS authorsRIS, CONCAT_WS(' ',au.last_name, ' ', ifnull(au.initials,''), ' ', au.first_name) as authorsCiteAs, CONCAT_WS(' ',au.first_name, IFNULL(CONCAT(' ', au.initials), ''), IFNULL(CONCAT(' ', au.last_name), '')) as authorsmodal , `au`.*, `af`.`ror_id`, `af`.`institution`, `af`.`department`, `af`.`country`, `af`.`city`, `af`.`address`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.institution,','),''), ifnull(concat(af.department,','),''), ifnull(concat(af.address,','),''), ifnull(concat(af.city,','),''), ifnull(concat(af.country,','),''), ifnull(concat(af.postal_code,','),''), ifnull(concat(af.phone,','),''), ifnull(concat(af.fax,','),''))) SEPARATOR '|')) as `author_affiliation`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.web_view,','),''))) SEPARATOR '|')) as `web_view` from `author` as `au` left join `author_affiliation` as `af` on `au`.`author_id` = `af`.`author_id` where `au`.`article_id` = '86573' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      2.65msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 86573
      Backtrace
      • 13. app/Models/Author.php:86
      • 14. app/Http/Controllers/ArticleController.php:2533
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      370μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2535
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `subtitle` from `journal` where `continues_publication_journal` = 1
      770μsalphaeurekaselec_live_10_06_2022Article.php#1960
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/Article.php:1960
      • 14. app/Http/Controllers/ArticleController.php:2062
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • Select j.subtitle, v.volume_id as volume_id,v.year_id,y.year as year,v.volume_name, v.total_no_of_issues, i.issue_id as issue_id,i.title as issue, i.publication_date as issue_pub_date from journal j join volume v on j.journal_id = v.journal_id join issue i on v.volume_id = i.volume_id join article a on a.issue_id = i.issue_id join year y on v.year_id = y.id where j.journal_id = 42 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      41.33msalphaeurekaselec_live_10_06_2022Issue.php#298
      Backtrace
      • 11. app/Models/Issue.php:298
      • 12. app/Http/Controllers/ArticleController.php:2068
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 1 and a.journal_id = 42 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      13.8msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2070
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 4 and a.journal_id = 42 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      11.84msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2071
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select pdf, html, epub, prc from `article_metrics` where `article_id` = 86573 limit 1
      310μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 86573
      Backtrace
      • 14. app/Models/Article.php:744
      • 15. app/Http/Controllers/ArticleController.php:2091
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from content_by_diseases where content_id = 86573 and content_type = 'article' order by status desc limit 1
      350μsalphaeurekaselec_live_10_06_2022Article.php#751
      Backtrace
      • 11. app/Models/Article.php:751
      • 12. app/Http/Controllers/ArticleController.php:2094
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `node_meta` where `nid` = 156644 limit 1
      270μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 156644
      Backtrace
      • 14. app/Models/Meta.php:30
      • 15. app/Http/Controllers/ArticleController.php:2101
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      310μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2108
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `tbl_ht_submission` as `h` where `h`.`subtitle` = 'CPPS' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      440μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: CPPS
      Backtrace
      • 13. app/Models/Article.php:2025
      • 14. app/Http/Controllers/ArticleController.php:2112
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '86573' and content_type = 'a' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      480μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2186
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '8696' and content_type = 'i' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      450μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2207
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '2493' and content_type = 'v' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      410μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2231
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51631602 and j.to_ip >=51631602 )) and ((j.from_date <= 1740460247 and j.to_date >= 1740460247 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2493) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51631602 and j.to_ip >=51631602 )) and ((j.from_date <= 1740460247 and j.to_date >= 1740460247 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2493) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51631602 and j.to_ip >=51631602 )) and ((j.from_date <= 1740460247 and j.to_date >= 1740460247 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2493)
      2.02msalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2272
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51631602 and j.to_ip >=51631602 )) and ((j.from_date <= 1740460247 and j.to_date >= 1740460247 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 8696) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51631602 and j.to_ip >=51631602 )) and ((j.from_date <= 1740460247 and j.to_date >= 1740460247 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 8696) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51631602 and j.to_ip >=51631602 )) and ((j.from_date <= 1740460247 and j.to_date >= 1740460247 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 8696)
      830μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2297
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51631602 and j.to_ip >=51631602 )) and ((j.from_date <= 1740460247 and j.to_date >= 1740460247 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 86573) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51631602 and j.to_ip >=51631602 )) and ((j.from_date <= 1740460247 and j.to_date >= 1740460247 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 86573) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51631602 and j.to_ip >=51631602 )) and ((j.from_date <= 1740460247 and j.to_date >= 1740460247 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 86573)
      910μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2329
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `first_page` < '22' and is_uploaded = 1 and issue_id = 8696 order by cast(first_page as SIGNED) desc limit 1
      730μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 22
      Backtrace
      • 14. app/Models/Article.php:1819
      • 15. app/Http/Controllers/ArticleController.php:2470
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `last_page` > '27' and is_uploaded = 1 and issue_id = 8696 order by cast(first_page as SIGNED) asc limit 1
      650μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 27
      Backtrace
      • 14. app/Models/Article.php:1831
      • 15. app/Http/Controllers/ArticleController.php:2472
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `language_id` from `multilanguage` where `short_code` = 'en'
      250μsalphaeurekaselec_live_10_06_2022ArticleController.php#2497
      Bindings
      • 0: en
      Backtrace
      • 14. app/Http/Controllers/ArticleController.php:2497
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select `source_lang_label`, `target_lang_label` from `multilanguage_labels` where `target_lang_id` = 1
      370μsalphaeurekaselec_live_10_06_2022MultiLanguage.php#23
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/MultiLanguage.php:23
      • 14. app/Http/Controllers/ArticleController.php:2498
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `id` from `multilanguage_article` where `article_id` = 86573 limit 1
      3.88msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 86573
      Backtrace
      • 16. app/Http/Controllers/ArticleController.php:2506
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 42 and `b`.`banner_from_date` <= 1740460248 and `b`.`banner_to_date` >= 1740460248 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.62msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 42
      • 3: 1740460248
      • 4: 1740460248
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 42 and `b`.`banner_from_date` <= 1740460248 and `b`.`banner_to_date` >= 1740460248 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.63msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 42
      • 3: 1740460248
      • 4: 1740460248
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='db88c3593f119c0fe0d2d980213f3e5e'
      320μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\MultiLanguage
    1MultiLanguage.php#?
        _token
        q5jiKnI5Izxn4PXnOCmvEdume7KZWkCt2bJWyfKk
        uc_cart_id
        db88c3593f119c0fe0d2d980213f3e5e
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/article/86573" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/86573
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:17 [ "x-https" => array:1 [ 0 => "1" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] "priority" => array:1 [ 0 => "u=0, i" ] "cookie" => array:1 [ 0 => "wayfindertarget=eyJpdiI6IkN4ZTRBNTBBS3FoUXQ1YS9mSzBlamc9PSIsInZhbHVlIjoiWHNFaXFyQlNwazBGR1RaK0dxOUdITDV1ck9OY0ltcm92cE84V2hvU0w5OD0iLCJtYWMiOiJiNTU3MDllZjE2ZDEyY2E5Yzk0ZDg2YmMwNjY4MDQyNWY0OTg5MDE5MjhiMTgxYmNiZjFjNjAzODBmMjdiMGNmIiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6IkN4ZTRBNTBBS3FoUXQ1YS9mSzBlamc9PSIsInZhbHVlIjoiWHNFaXFyQlNwazBGR1RaK0dxOUdITDV1ck9OY0ltcm92cE84V2hvU0w5OD0iLCJtYWMiOiJiNTU3MDllZjE2ZDEy" ] "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" ] ]
        request_cookies
        0 of 0
        array:1 [ "wayfindertarget" => null ]
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Tue, 25 Feb 2025 05:10:48 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6Imp2cG40VXhGaXJhWE5kNEdhL0EwM1E9PSIsInZhbHVlIjoiejFOaEI4eEVFb3kvMytpQzR5bHpLYVRlMVRvTktualF0S0lraGhtWTVya0plbDY4bXpJR0l4bW5Oc012UnZIZG9jRms0bHhmQm9TSXlYQVdmRmN3d2VrTkdKS3BITjg4YTF4aHpCL3VZZDNnRVExdDEzVGswUnNhb1l0T3VZeHIiLCJtYWMiOiJlZWExMjI3YjU5YzFhY2IyOTU1YmEwOTEyMGU1YmVmYzE5MDE4YmRkYWQ1NTg4ODFiY2M0MTA1NmM1OTBkZThjIiwidGFnIjoiIn0%3D; expires=Thu, 27 Feb 2025 17:10:48 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6Imp2cG40VXhGaXJhWE5kNEdhL0EwM1E9PSIsInZhbHVlIjoiejFOaEI4eEVFb3kvMytpQzR5bHpLYVRlMVRvTktualF0S0lraGhtWTVya0plbDY4bXpJR0l4bW5Oc012UnZIZG9jRms0b" 1 => "alphaeurekaselectnet_session=eyJpdiI6IjBrRmV3dGszemJWa1VSajhLMWFId0E9PSIsInZhbHVlIjoiSlRNY0RCZ0xXbHJSZktld2I0Z3hVa3NpZ2dSZ0ZVYi9YbFRqMXhxZjJldm9nalRMM1FFTnZHbDVWcGFQUXN6YnoxVCtHTGIwbnJ4Y3V5WjZqekhsSXE4c3REdTgzTXNhTWJVeWVKVWdzcFFicG85aC8veTI4NGdBZHVQQ0NsKy8iLCJtYWMiOiJmMzUzZTU1MjBmYmUwZDY3ODg5OTMzYTcwZWVlNzIyZjk0NTY2Y2Y5ZDliYjUzZDc2NWY4ZWQ2NTYxZGU5M2ZiIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6IjBrRmV3dGszemJWa1VSajhLMWFId0E9PSIsInZhbHVlIjoiSlRNY0RCZ0xXbHJSZktld2I0Z3hVa3NpZ2dSZ0ZVYi9YbFRqMXhxZjJldm9nalRMM1FFTnZHbDV" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6Imp2cG40VXhGaXJhWE5kNEdhL0EwM1E9PSIsInZhbHVlIjoiejFOaEI4eEVFb3kvMytpQzR5bHpLYVRlMVRvTktualF0S0lraGhtWTVya0plbDY4bXpJR0l4bW5Oc012UnZIZG9jRms0bHhmQm9TSXlYQVdmRmN3d2VrTkdKS3BITjg4YTF4aHpCL3VZZDNnRVExdDEzVGswUnNhb1l0T3VZeHIiLCJtYWMiOiJlZWExMjI3YjU5YzFhY2IyOTU1YmEwOTEyMGU1YmVmYzE5MDE4YmRkYWQ1NTg4ODFiY2M0MTA1NmM1OTBkZThjIiwidGFnIjoiIn0%3D; expires=Thu, 27-Feb-2025 17:10:48 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6Imp2cG40VXhGaXJhWE5kNEdhL0EwM1E9PSIsInZhbHVlIjoiejFOaEI4eEVFb3kvMytpQzR5bHpLYVRlMVRvTktualF0S0lraGhtWTVya0plbDY4bXpJR0l4bW5Oc012UnZIZG9jRms0b" 1 => "alphaeurekaselectnet_session=eyJpdiI6IjBrRmV3dGszemJWa1VSajhLMWFId0E9PSIsInZhbHVlIjoiSlRNY0RCZ0xXbHJSZktld2I0Z3hVa3NpZ2dSZ0ZVYi9YbFRqMXhxZjJldm9nalRMM1FFTnZHbDVWcGFQUXN6YnoxVCtHTGIwbnJ4Y3V5WjZqekhsSXE4c3REdTgzTXNhTWJVeWVKVWdzcFFicG85aC8veTI4NGdBZHVQQ0NsKy8iLCJtYWMiOiJmMzUzZTU1MjBmYmUwZDY3ODg5OTMzYTcwZWVlNzIyZjk0NTY2Y2Y5ZDliYjUzZDc2NWY4ZWQ2NTYxZGU5M2ZiIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6IjBrRmV3dGszemJWa1VSajhLMWFId0E9PSIsInZhbHVlIjoiSlRNY0RCZ0xXbHJSZktld2I0Z3hVa3NpZ2dSZ0ZVYi9YbFRqMXhxZjJldm9nalRMM1FFTnZHbDV" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "q5jiKnI5Izxn4PXnOCmvEdume7KZWkCt2bJWyfKk" "uc_cart_id" => "db88c3593f119c0fe0d2d980213f3e5e" "_previous" => array:1 [ "url" => "https://alpha.eurekaselect.com/article/86573" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-25 05:10:48GET/article/86573314361