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Protein & Peptide Letters

Editor-in-Chief

ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

General Research Article

Beyond B-Cell Epitopes: Curating Positive Data on Antipeptide Paratope Binding to Support Peptide-Based Vaccine Design

Author(s): Salvador Eugenio C. Caoili*

Volume 28, Issue 8, 2021

Published on: 18 February, 2021

Page: [953 - 962] Pages: 10

DOI: 10.2174/0929866528666210218215624

Price: $65

Abstract

Background: B-cell epitope prediction is a computational approach originally developed to support the design of peptide-based vaccines for inducing protective antibody-mediated immunity, as exemplified by neutralization of biological activity (e.g., pathogen infectivity). Said approach is benchmarked against experimentally obtained data on paratope-epitope binding; but such data are curated primarily on the basis of immune-complex structure, obscuring the role of antigen conformational disorder in the underlying immune recognition process.

Objective: This work aimed to critically analyze the curation of epitope-paratope binding data that are relevant to B-cell epitope prediction for peptide-based vaccine design.

Methods: Database records on neutralizing monoclonal antipeptide antibody immune-complex structure were retrieved from the Immune Epitope Database (IEDB) and analyzed in relation to other data from both IEDB and external sources including the Protein Data Bank (PDB) and published literature, with special attention to data on conformational disorder among paratope-bound and unbound peptidic antigens.

Results: Data analysis revealed key examples of antipeptide antibodies that recognize conformationally disordered B-cell epitopes and thereby neutralize the biological activity of cognate targets (e.g., proteins and pathogens), with inconsistency noted in the mapping of some epitopes due to reliance on immune-complex structural details, which vary even among experiments utilizing the same paratope-epitope combination (e.g., with the epitope forming part of a peptide or a protein).

Conclusion: The results suggest an alternative approach to curating paratope-epitope binding data based on neutralization of biological activity by polyclonal antipeptide antibodies, with reference to immunogenic peptide sequences and their conformational disorder in unbound antigen structures.

Keywords: Epitopes, paratopes, antigens, antibodies, peptides, proteins, vaccines, conformational disorder.

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[1]
Caoili, S.E. Antibodies, synthetic peptides and related constructs for planetary health based on green chemistry in the Anthropocene. Future Sci. OA, 2018, 4(3), FSO275.
[http://dx.doi.org/10.4155/fsoa-2017-0101] [PMID: 29568564]
[2]
Nandy, A.; Dey, S.; Roy, P.; Basak, S.C. Epidemics and peptide vaccine response: a brief review. Curr. Top. Med. Chem., 2018, 18(26), 2202-2208.
[http://dx.doi.org/10.2174/1568026618666181112144745] [PMID: 30417788]
[3]
Arnon, R. Synthetic vaccines--a dream or reality. Adv. Exp. Med. Biol., 1972, 31(0), 209-222.
[http://dx.doi.org/10.1007/978-1-4684-3225-1_17] [PMID: 4137226]
[4]
Malonis, R.J.; Lai, J.R.; Vergnolle, O. Peptide-based vaccines: current progress and future challenges. Chem. Rev., 2020, 120(6), 3210-3229.
[http://dx.doi.org/10.1021/acs.chemrev.9b00472] [PMID: 31804810]
[5]
Johnson, A.T. The technology hype cycle. IEEE Pulse, 2015, 6(2), 50.
[http://dx.doi.org/10.1109/MPUL.2014.2386491] [PMID: 25946758]
[6]
Shinnick, T.M.; Sutcliffe, J.G.; Green, N.; Lerner, R.A. Synthetic peptide immunogens as vaccines. Annu. Rev. Microbiol., 1983, 37, 425-446.
[http://dx.doi.org/10.1146/annurev.mi.37.100183.002233] [PMID: 6357058]
[7]
Brown, F. The Leeuwenhoek Lecture, 1993. Peptide vaccines: dream or reality? Philos. Trans. R. Soc. Lond. B Biol. Sci., 1994, 344(1308), 213-219.
[http://dx.doi.org/10.1098/rstb.1994.0062] [PMID: 7521966]
[8]
Hans, D.; Young, P.R.; Fairlie, D.P. Current status of short synthetic peptides as vaccines. Med. Chem., 2006, 2(6), 627-646.
[http://dx.doi.org/10.2174/1573406410602060627] [PMID: 17105445]
[9]
Trier, N.; Hansen, P.; Houen, G. Peptides, antibodies, peptide antibodies and more. Int. J. Mol. Sci., 2019, 20(24), 6289.
[http://dx.doi.org/10.3390/ijms20246289] [PMID: 31847088]
[10]
Potocnakova, L.; Bhide, M.; Pulzova, L.B. An introduction to B-cell epitope mapping and in silico epitope prediction. J. Immunol. Res., 2016, 2016, 6760830.
[http://dx.doi.org/10.1155/2016/6760830] [PMID: 28127568]
[11]
Sanchez-Trincado, J.L.; Gomez-Perosanz, M.; Reche, P.A. Fundamentals and methods for T- and B-cell epitope prediction. J. Immunol. Res., 2017, 2017, 2680160.
[http://dx.doi.org/10.1155/2017/2680160] [PMID: 29445754]
[12]
Hos, B.J.; Tondini, E.; van Kasteren, S.I.; Ossendorp, F. Approaches to improve chemically defined synthetic peptide vaccines. Front. Immunol., 2018, 9, 884.
[http://dx.doi.org/10.3389/fimmu.2018.00884] [PMID: 29755468]
[13]
Patronov, A.; Doytchinova, I. T-cell epitope vaccine design by immunoinformatics. Open Biol., 2013, 3(1), 120139.
[http://dx.doi.org/10.1098/rsob.120139] [PMID: 23303307]
[14]
Desai, D.V.; Kulkarni-Kale, U. T-cell epitope prediction methods: an overview. Methods Mol. Biol., 2014, 1184, 333-364.
[http://dx.doi.org/10.1007/978-1-4939-1115-8_19] [PMID: 25048134]
[15]
Oyarzun, P.; Kobe, B. Computer-aided design of T-cell epitope-based vaccines: addressing population coverage. Int. J. Immunogenet., 2015, 42(5), 313-321.
[http://dx.doi.org/10.1111/iji.12214] [PMID: 26211755]
[16]
Chen, S.W.; Van Regenmortel, M.H.; Pellequer, J.L. Structure-activity relationships in peptide-antibody complexes: implications for epitope prediction and development of synthetic peptide vaccines. Curr. Med. Chem., 2009, 16(8), 953-964.
[http://dx.doi.org/10.2174/092986709787581914] [PMID: 19275605]
[17]
MacRaild, C.A.; Richards, J.S.; Anders, R.F.; Norton, R.S. Antibody recognition of disordered antigens. Structure, 2016, 24(1), 148-157.
[http://dx.doi.org/10.1016/j.str.2015.10.028] [PMID: 26712277]
[18]
Kaufmann, S.H.E. Immunology’s coming of age. Front. Immunol., 2019, 10, 684.
[http://dx.doi.org/10.3389/fimmu.2019.00684] [PMID: 31001278]
[19]
Jerne, N.K. Immunological speculations. Annu. Rev. Microbiol., 1960, 14, 341-358.
[http://dx.doi.org/10.1146/annurev.mi.14.100160.002013] [PMID: 13789973]
[20]
Van Regenmortel, M.H. What is a B-cell epitope? Methods Mol. Biol., 2009, 524, 3-20.
[http://dx.doi.org/10.1007/978-1-59745-450-6_1] [PMID: 19377933]
[21]
Skwarczynski, M.; Toth, I. Peptide-based synthetic vaccines. Chem. Sci. (Camb.), 2016, 7(2), 842-854.
[http://dx.doi.org/10.1039/C5SC03892H] [PMID: 28791117]
[22]
Van Regenmortel, M.H. From absolute to exquisite specificity. Reflections on the fuzzy nature of species, specificity and antigenic sites. J. Immunol. Methods, 1998, 216(1-2), 37-48.
[http://dx.doi.org/10.1016/S0022-1759(98)00069-6] [PMID: 9760214]
[23]
Martini, S.; Nielsen, M.; Peters, B.; Sette, A. The Immune Epitope Database and Analysis Resource Program 2003-2018: reflections and outlook. Immunogenetics, 2020, 72(1-2), 57-76.
[http://dx.doi.org/10.1007/s00251-019-01137-6] [PMID: 31761977]
[24]
Caoili, S.E. Hybrid methods for B-cell epitope prediction. Methods Mol. Biol., 2014, 1184, 245-283.
[http://dx.doi.org/10.1007/978-1-4939-1115-8_14] [PMID: 25048129]
[25]
Burley, S.K.; Berman, H.M.; Bhikadiya, C.; Bi, C.; Chen, L.; Di Costanzo, L.; Christie, C.; Dalenberg, K.; Duarte, J.M.; Dutta, S.; Feng, Z.; Ghosh, S.; Goodsell, D.S.; Green, R.K.; Guranovic, V.; Guzenko, D.; Hudson, B.P.; Kalro, T.; Liang, Y.; Lowe, R.; Namkoong, H.; Peisach, E.; Periskova, I.; Prlic, A.; Randle, C.; Rose, A.; Rose, P.; Sala, R.; Sekharan, M.; Shao, C.; Tan, L.; Tao, Y.P.; Valasatava, Y.; Voigt, M.; Westbrook, J.; Woo, J.; Yang, H.; Young, J.; Zhuravleva, M.; Zardecki, C. RCSB Protein Data Bank: biological macromolecular structures enabling research and education in fundamental biology, biomedicine, biotechnology and energy. Nucleic Acids Res., 2019, 47(D1), D464-D474.
[http://dx.doi.org/10.1093/nar/gky1004] [PMID: 30357411]
[26]
Lu, Z. PubMed and beyond: a survey of web tools for searching biomedical literature. Database (Oxford), 2011, 2011, baq036.
[http://dx.doi.org/10.1093/database/baq036] [PMID: 21245076]
[27]
Kabsch, W.; Sander, C. Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers, 1983, 22(12), 2577-2637.
[http://dx.doi.org/10.1002/bip.360221211] [PMID: 6667333]
[28]
DeForte, S.; Uversky, V.N. Order, disorder, and everything in between. Molecules, 2016, 21(8), 1090.
[http://dx.doi.org/10.3390/molecules21081090] [PMID: 27548131]
[29]
Uversky, V.N. Flexibility of the “rigid” classics or rugged bottom of the folding funnels of myoglobin, lysozyme, RNase A, chymotrypsin, cytochrome c, and carboxypeptidase A1. Intrinsically Disord. Proteins, 2017, 5(1), e1355205.
[http://dx.doi.org/10.1080/21690707.2017.1355205] [PMID: 30250772]
[30]
Dauter, Z.; Wlodawer, A. Progress in protein crystallography. Protein Pept. Lett., 2016, 23(3), 201-210.
[http://dx.doi.org/10.2174/0929866523666160106153524] [PMID: 26732246]
[31]
Arai, M. Unified understanding of folding and binding mechanisms of globular and intrinsically disordered proteins. Biophys. Rev., 2018, 10(2), 163-181.
[http://dx.doi.org/10.1007/s12551-017-0346-7] [PMID: 29307002]
[32]
Shingler, K.L.; Cifuente, J.O.; Ashley, R.E.; Makhov, A.M.; Conway, J.F.; Hafenstein, S. The enterovirus 71 procapsid binds neutralizing antibodies and rescues virus infection in vitro. J. Virol., 2015, 89(3), 1900-1908.
[http://dx.doi.org/10.1128/JVI.03098-14] [PMID: 25428877]
[33]
Grzesiek, S.; Döbeli, H.; Gentz, R.; Garotta, G.; Labhardt, A.M.; Bax, A. 1H, 13C, and 15N NMR backbone assignments and secondary structure of human interferon-gamma. Biochemistry, 1992, 31(35), 8180-8190.
[http://dx.doi.org/10.1021/bi00150a009] [PMID: 1525157]
[34]
Vanhaverbeke, C.; Simorre, J.P.; Sadir, R.; Gans, P.; Lortat-Jacob, H. NMR characterization of the interaction between the C-terminal domain of interferon-gamma and heparin-derived oligosaccharides. Biochem. J., 2004, 384(Pt 1), 93-99.
[http://dx.doi.org/10.1042/BJ20040757] [PMID: 15270718]
[35]
Liao, S.Y.; Fritzsching, K.J.; Hong, M. Conformational analysis of the full-length M2 protein of the influenza A virus using solid-state NMR. Protein Sci., 2013, 22(11), 1623-1638.
[http://dx.doi.org/10.1002/pro.2368] [PMID: 24023039]
[36]
Caruso, A.; Viani, E.; Tiberio, L.; Pollara, P.; Monti, E.; Bonfanti, C.; Gao, J.; Landolfo, S.; Balsari, A.; Turano, A. Inhibition of the biological activity of human interferon-gamma by antipeptide antibodies. J. Interferon Res., 1992, 12(1), 49-54.
[http://dx.doi.org/10.1089/jir.1992.12.49] [PMID: 1573282]
[37]
Caoili, S.E. Benchmarking B-cell epitope prediction for the design of peptide-based vaccines: problems and prospects. J. Biomed. Biotechnol., 2010, 2010, 910524.
[http://dx.doi.org/10.1155/2010/910524] [PMID: 20368996]
[38]
Caoili, S.E. An integrative structure-based framework for predicting biological effects mediated by antipeptide antibodies. J. Immunol. Methods, 2015, 427, 19-29.
[http://dx.doi.org/10.1016/j.jim.2015.09.002] [PMID: 26410103]
[39]
Grifoni, A.; Sidney, J.; Zhang, Y.; Scheuermann, R.H.; Peters, B.; Sette, A. A sequence homology and bioinformatic approach can predict candidate targets for immune responses to SARS-CoV-2. Cell Host Microbe, 2020, 27(4), 671-680.e2.
[http://dx.doi.org/10.1016/j.chom.2020.03.002] [PMID: 32183941]
[40]
Kalita, P.; Padhi, A.K.; Zhang, K.Y.J.; Tripathi, T. Design of a peptide-based subunit vaccine against novel coronavirus SARS-CoV-2. Microb. Pathog., 2020, 145, 104236.
[http://dx.doi.org/10.1016/j.micpath.2020.104236] [PMID: 32376359]
[41]
Lin, L.; Ting, S.; Yufei, H.; Wendong, L.; Yubo, F.; Jing, Z. Epitope-based peptide vaccines predicted against novel coronavirus disease caused by SARS-CoV-2. Virus Res., 2020, 288, 198082.
[http://dx.doi.org/10.1016/j.virusres.2020.198082] [PMID: 32621841]
[42]
Crooke, S.N.; Ovsyannikova, I.G.; Kennedy, R.B.; Poland, G.A. Immunoinformatic identification of B cell and T cell epitopes in the SARS-CoV-2 proteome. Sci. Rep., 2020, 10(1), 14179.
[http://dx.doi.org/10.1038/s41598-020-70864-8] [PMID: 32843695]
[43]
Singh, A.; Thakur, M.; Sharma, L.K.; Chandra, K. Designing a multi-epitope peptide based vaccine against SARS-CoV-2. Sci. Rep., 2020, 10(1), 16219.
[http://dx.doi.org/10.1038/s41598-020-73371-y] [PMID: 33004978]
[44]
Khairkhah, N.; Aghasadeghi, M.R.; Namvar, A.; Bolhassani, A. Design of novel multiepitope constructs-based peptide vaccine against the structural S, N and M proteins of human COVID-19 using immunoinformatics analysis. PLoS One, 2020, 15(10), e0240577.
[http://dx.doi.org/10.1371/journal.pone.0240577] [PMID: 33057358]
[45]
Di Natale, C.; Marasco, D.; La Manna, S.; De Benedictis, I.; Brandi, P. Perspectives in peptide-based vaccination strategies for SARS-CoV-2 pandemic. Front. Pharmacol., 2020, 11, 578382.
[http://dx.doi.org/10.3389/fphar.2020.578382] [PMID: 33343349]

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    • 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=114369
      930μsalphaeurekaselec_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` = 51 limit 1
      1.04msalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 51
      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=51) and sj.journal_id!=51 group by `j`.`nid`) as `aggregate_table`
      1.17msalphaeurekaselec_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=51) and sj.journal_id!=51 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      1.03msalphaeurekaselec_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=51) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      4.09msalphaeurekaselec_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=51) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      3.57msalphaeurekaselec_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` = '114369'
      930μsalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 114369
      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` = '114369'
      2.75msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 114369
      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` = '114369' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      1.53msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 114369
      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
      220μsalphaeurekaselec_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
      430μsalphaeurekaselec_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 = 51 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      22.5msalphaeurekaselec_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 = 51 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      18.27msalphaeurekaselec_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 = 51 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      16.38msalphaeurekaselec_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` = 114369 limit 1
      230μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 114369
      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 = 114369 and content_type = 'article' order by status desc limit 1
      250μsalphaeurekaselec_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 a.nid article_nid,a.title article_title,j.title journal_title from content_by_diseases cd inner join article a on a.article_id=cd.content_id inner join journal j on j.journal_id=a.journal_id where cd.pid = 295 and cd.sub_disease_id = 300 and content_id!=114369 and cd.content_type = 'article' order by rand() limit 20
      146msalphaeurekaselec_live_10_06_2022Article.php#769
      Backtrace
      • 11. app/Models/Article.php:769
      • 12. app/Http/Controllers/ArticleController.php:2098
      • 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` = 191579 limit 1
      220μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 191579
      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
      200μsalphaeurekaselec_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` = 'PPL' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      250μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: PPL
      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 = '114369' 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) )
      340μsalphaeurekaselec_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 = '10790' 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) )
      260μsalphaeurekaselec_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 = '2944' 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) )
      240μsalphaeurekaselec_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 <= 314566045 and j.to_ip >=314566045 )) and ((j.from_date <= 1739834394 and j.to_date >= 1739834394 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2944) 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 <= 314566045 and j.to_ip >=314566045 )) and ((j.from_date <= 1739834394 and j.to_date >= 1739834394 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2944) 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 <= 314566045 and j.to_ip >=314566045 )) and ((j.from_date <= 1739834394 and j.to_date >= 1739834394 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2944)
      6.46msalphaeurekaselec_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 <= 314566045 and j.to_ip >=314566045 )) and ((j.from_date <= 1739834394 and j.to_date >= 1739834394 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 10790) 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 <= 314566045 and j.to_ip >=314566045 )) and ((j.from_date <= 1739834394 and j.to_date >= 1739834394 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 10790) 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 <= 314566045 and j.to_ip >=314566045 )) and ((j.from_date <= 1739834394 and j.to_date >= 1739834394 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 10790)
      550μsalphaeurekaselec_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 <= 314566045 and j.to_ip >=314566045 )) and ((j.from_date <= 1739834394 and j.to_date >= 1739834394 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 114369) 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 <= 314566045 and j.to_ip >=314566045 )) and ((j.from_date <= 1739834394 and j.to_date >= 1739834394 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 114369) 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 <= 314566045 and j.to_ip >=314566045 )) and ((j.from_date <= 1739834394 and j.to_date >= 1739834394 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 114369)
      540μsalphaeurekaselec_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` < '953' and is_uploaded = 1 and issue_id = 10790 order by cast(first_page as SIGNED) desc limit 1
      480μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 953
      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` > '962' and is_uploaded = 1 and issue_id = 10790 order by cast(first_page as SIGNED) asc limit 1
      360μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 962
      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'
      180μsalphaeurekaselec_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
      180μsalphaeurekaselec_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` = 114369 limit 1
      2.39msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 114369
      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` = 51 and `b`.`banner_from_date` <= 1739834394 and `b`.`banner_to_date` >= 1739834394 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.1msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 51
      • 3: 1739834394
      • 4: 1739834394
      • 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` = 51 and `b`.`banner_from_date` <= 1739834394 and `b`.`banner_to_date` >= 1739834394 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.07msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 51
      • 3: 1739834394
      • 4: 1739834394
      • 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='bebd6b7b7cae0bc4b3ec4e823a98e924'
      190μsalphaeurekaselec_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
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        uc_cart_id
        bebd6b7b7cae0bc4b3ec4e823a98e924
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/article/114369" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
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        status_code
        200
        
        status_text
        OK
        format
        html
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        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
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        response_headers
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        ClearShow all
        Date ↕MethodURLData
        #12025-02-17 23:19:54GET/article/114369414371