Advances in Alzheimer's Research

Volume: 2

Methods for Studying and Structure–Function Relationships of Non-Fibrillar Protein Assemblies in Alzheimer's Disease and Related Disorders

Author(s): Farid Rahimi and Gal Bitan

Pp: 291-374 (84)

DOI: 10.2174/9781608058525114020014

* (Excluding Mailing and Handling)

Abstract

Several neurodegenerative diseases, including Alzheimer's, Parkinson's, Huntington's, and prion diseases, are characterized by intra- and/or extracellular deposition of fibrillar proteinaceous aggregates, and by extensive, neuron loss. Related non-neuropathic systemic diseases, e.g., light-chain and senile systemic amyloidoses, and other organ-specific diseases, such as dialysis-related amyloidosis and type-2 diabetes, also are characterized by deposition of aggregated proteins. It is debated whether these hallmark lesions are causative. Substantial evidence suggests that the aggregates are the end state of protein misfolding whereas the actual culprits likely are transient, non-fibrillar assemblies preceding the aggregates. The non-fibrillar, oligomeric assemblies are believed to initiate pathogenesis, leading to synaptic dysfunction, neuron loss, and pathognomonic brain atrophy. It is hypothesized that nonfibrillar assemblies or fibril-derived fragments may promote anatomical progression of pathology, or even disease transmissibility, akin to misfolded prions.

Amyloid β-protein (Aβ), which is believed to cause Alzheimer's disease, is considered an archetypal amyloidogenic protein. Intense studies have led to nominal, functional, and structural descriptions of oligomeric Aβ assemblies. However, the dynamic and metastable nature of Aβ oligomers renders their study difficult. Different results generated using different methodologies under different experimental settings further complicate this complex area of research and identification of the exact pathogenic assemblies in vivo seems daunting.

In this chapter we review structural, functional, and biological experiments used to produce and study non-fibrillar Aβ assemblies, and highlight similar studies of proteins involved in related diseases. We discuss challenges that contemporary researchers are facing and future research prospects in this demanding, yet highly important, field.

Related Journals
Related Books
© 2025 Bentham Science Publishers | Privacy Policy
Request history8.2.27PHP Version352msRequest Duration26MBMemory UsageGET chapter/{id}/{param?}Route
  • warninglog[23:25:17] LOG.warning: Optional parameter $id declared before required parameter $request is implic...
  • Booting (148ms)time
  • Application (205ms)time
  • 1 x Application (58.12%)
    205ms
    1 x Booting (41.88%)
    148ms
    12 templates were rendered
    • ebook.chapter_detailschapter_details.blade.php#?blade
    • layouts.chapter_header_sectionchapter_header_section.blade.php#?blade
    • ebook.chapter_top_bannerchapter_top_banner.blade.php#?blade
    • ebook.chapter_bottom_bannerchapter_bottom_banner.blade.php#?blade
    • ebook.ebook_right_bannerebook_right_banner.blade.php#?blade
    • includes.inc_related_journalsinc_related_journals.blade.php#?blade
    • includes.inc_related_ebooksinc_related_ebooks.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 chapter/{id}/{param?}
    middleware
    web, check_user_access
    controller
    App\Http\Controllers\ChapterController@GetChapterDetails
    namespace
    App\Http\Controllers
    where
    as
    chapter
    file
    app/Http/Controllers/ChapterController.php:1350-1704
    19 statements were executed119ms
    • 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 ('316440840','',1,1739834717,1739834717) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1739834717
      4.09msalphaeurekaselec_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 ('316440840','/chapter/6729',1,1739834717,1739834717)
      270μsalphaeurekaselec_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 >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) 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 >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) 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 >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) 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 >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) 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 >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) 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 >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 316440840 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316440840) limit 1
      89.93msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 316440840
      • 1: 316440840
      • 2: 316440840
      • 3: 316440840
      • 4: 316440840
      • 5: 316440840
      • 6: 316440840
      • 7: 316440840
      • 8: 316440840
      • 9: 316440840
      • 10: 316440840
      • 11: 316440840
      • 12: 316440840
      • 13: 316440840
      • 14: 316440840
      • 15: 316440840
      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 * from `chapter` where `chapter_id` = '6729' limit 1
      1.12msalphaeurekaselec_live_10_06_2022ChapterController.php#1406
      Bindings
      • 0: 6729
      Backtrace
      • 16. app/Http/Controllers/ChapterController.php:1406
      • 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 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`.`chapter_id` = '6729' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      980μsalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 6729
      Backtrace
      • 13. app/Models/Author.php:86
      • 14. app/Http/Controllers/ChapterController.php:1411
      • 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 `keywords` where `chapter_id` = '6729'
      1.05msalphaeurekaselec_live_10_06_2022ChapterController.php#1415
      Bindings
      • 0: 6729
      Backtrace
      • 15. app/Http/Controllers/ChapterController.php:1415
      • 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
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select * from `ebook` where `ebook_id` = 366 limit 1
      3.83msalphaeurekaselec_live_10_06_2022ChapterController.php#1430
      Bindings
      • 0: 366
      Backtrace
      • 16. app/Http/Controllers/ChapterController.php:1430
      • 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 count(*) as aggregate 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` = `e`.`ebook_id` where subject_id IN (select subject_id FROM subject_ebook WHERE ebook_id=366) and se.ebook_id!=366 and v.ebook_status='1'
      9.54msalphaeurekaselec_live_10_06_2022Subject.php#238
      Backtrace
      • 16. app/Models/Subject.php:238
      • 17. app/Http/Controllers/ChapterController.php:1434
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 19. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select distinct 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` = `e`.`ebook_id` where subject_id IN (select subject_id FROM subject_ebook WHERE ebook_id=366) and se.ebook_id!=366 and v.ebook_status='1' limit 10 offset 0
      1.14msalphaeurekaselec_live_10_06_2022Subject.php#238
      Backtrace
      • 14. app/Models/Subject.php:238
      • 15. app/Http/Controllers/ChapterController.php:1434
      • 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 count(*) as aggregate from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where subject_id IN (select subject_id FROM subject_ebook WHERE ebook_id=366)
      590μsalphaeurekaselec_live_10_06_2022Subject.php#255
      Backtrace
      • 16. app/Models/Subject.php:255
      • 17. app/Http/Controllers/ChapterController.php:1435
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 19. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select distinct j.nid as journal_nid,j.title,j.subtitle,j.issn,j.eissn,j.keyword,sj.journal_id,j.image_file_name,j.flyer_link from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where subject_id IN (select subject_id FROM subject_ebook WHERE ebook_id=366) limit 10 offset 0
      660μsalphaeurekaselec_live_10_06_2022Subject.php#255
      Backtrace
      • 14. app/Models/Subject.php:255
      • 15. app/Http/Controllers/ChapterController.php:1435
      • 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 `e`.*, `a`.*, `y`.`year`, `e`.`ebook_volume_id` as `ebook_volume_id`, `a`.`ebook_volume_id` as `ebk_vol_id`, `e`.`ebook_id` as `ebk_ebook_id` from `ebook_volume` as `e` left join `author` as `a` on `e`.`ebook_volume_id` = `a`.`ebook_volume_id` left join `year` as `y` on `y`.`id` = `e`.`year_id` where `e`.`ebook_volume_id` = 1532 and `e`.`is_uploaded` = 1
      950μsalphaeurekaselec_live_10_06_2022EbookVolume.php#271
      Bindings
      • 0: 1532
      • 1: 1
      Backtrace
      • 13. app/Models/EbookVolume.php:271
      • 14. app/Http/Controllers/ChapterController.php:1438
      • 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(*) rcd from `ebook_volume` where `ebook_id` = 366 and ebook_volume_id <> 1532 limit 1
      400μsalphaeurekaselec_live_10_06_2022EbookVolume.php#999
      Bindings
      • 0: 366
      Backtrace
      • 14. app/Models/EbookVolume.php:999
      • 15. app/Http/Controllers/ChapterController.php:1462
      • 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 count(*) as total_count, content_type_access_id as access_type from ebook_access where content_type_id = '6729' and content_type = 'c' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      400μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ChapterController.php:1465
      • 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 ebook_access where content_type_id = '1532' 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) )
      400μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ChapterController.php:1478
      • 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,"ebook_volume" as access_level,"" as chapter_id from `user_access_ebook_volume_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316440840 and j.to_ip >=316440840 )) and ((j.from_date <= 1739834717 and j.to_date >= 1739834717 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 1532) 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,"ebook_volume" as access_level,"" as chapter_id from `user_access_ebook_volume_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316440840 and j.to_ip >=316440840 )) and ((j.from_date <= 1739834717 and j.to_date >= 1739834717 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 1532) 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,"ebook_volume" as access_level,"" as chapter_id from `user_access_ebook_volume_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316440840 and j.to_ip >=316440840 )) and ((j.from_date <= 1739834717 and j.to_date >= 1739834717 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 1532)
      890μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1518
      • 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,"chapter" as access_level, j.chapter_id from `user_access_chapter_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316440840 and j.to_ip >=316440840 )) and ((j.from_date <= 1739834717 and j.to_date >= 1739834717 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 6729) 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,"chapter" as access_level, j.chapter_id from `user_access_chapter_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316440840 and j.to_ip >=316440840 )) and ((j.from_date <= 1739834717 and j.to_date >= 1739834717 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 6729) 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,"chapter" as access_level, j.chapter_id from `user_access_chapter_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 316440840 and j.to_ip >=316440840 )) and ((j.from_date <= 1739834717 and j.to_date >= 1739834717 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 6729)
      930μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1549
      • 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 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` where `b`.`banner_ebook` = 1 and `bd`.`content_type` = 'B' and `bd`.`content_id` = 1532 and `b`.`banner_from_date` <= 1739834717 and `b`.`banner_to_date` >= 1739834717 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.71msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 1532
      • 3: 1739834717
      • 4: 1739834717
      • 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='0a4f6da223b447dedf7613234a58dc88'
      300μsalphaeurekaselec_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\Chapter
    1Chapter.php#?
    App\Models\Keywords
    1Keywords.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        iJLcvEum1h9MAcWhqi2xHLsTgq7WoNTB8dHcMXjV
        uc_cart_id
        0a4f6da223b447dedf7613234a58dc88
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/6729" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/6729
        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 => "fpestid=lbwvGiXYriJVwA0g4i4Z5mNBVQ18k4lyIQO0xc9NQFqIW1_8-KR3YjdX9XGmJUZ0OicdEg; wayfindertarget=eyJpdiI6IlIwSDNLZUlPOTN0UUt5Q2hCNkJ5OUE9PSIsInZhbHVlIjoiMTQ3TzdpN291UFIzVnViemVJMHRoMHVmbWhMS2RvdlZ1R0dVNUYrcndDU3UySVNtTnBGV0FWenVjWUlZY1IyMSIsIm1hYyI6ImFkZWJmYjYzNGJlYmRhN2FjNTdlNmU3ZjRjMDc1YWRmNTNjNzFhZmU5OGRiYWM5MDFhMWNmYzI5ZGY4MWYwN2UiLCJ0YWciOiIifQ%3D%3D; XSRF-TOKEN=eyJpdiI6IjdYd0ZmYWErQXowcWgrcEJBS2h3b3c9PSIsInZhbHVlIjoidDFodHdEMWR4ckpkT1hDbFB3ZGdkbGRzMlE4ZXF4aHB0bDh2VXBtS2xXaUZ3Y0lFMTMyWm5jWEo5MGtxN3Bub3BKWU5TNnRyQUNFQmZKblFOMzVKeENSR0dQdFNDY00vTzgvN2RWK3JyNnFMYTZwbXVLd2I2aG5lMzl4aWVyYzAiLCJtYWMiOiJkMWYyNTA3Yzc2N2I4MDBiODg4NWM1NzYyNmUyYmE1M2VkNmRhMDRkMDY5MDAzNTYwNjcyNDc1MDU1YTA1Y2I5IiwidGFnIjoiIn0%3D; alphaeurekaselectnet_session=eyJpdiI6IkFmeTZTUHYyb253UUZMY0haaUhaelE9PSIsInZhbHVlIjoiM3Vuam5qc21qMmNQSDhjZ2Q1b25vTjNaN05BM2VOajZ5REdBdXZLSE40bEFoank1Y2Z4YUdUMEVkVGgzZEZiajdUVkJGK2lKVWhIemZkQVA5M2szT1RNZ0wvekdGcjM4QlZUWlVaY3hNMUhZazFwTS9ZYjBwbjhXQkRubzQxK3QiLCJtYWMiOiI0YjZiMGQ4NmJiMmRjODYxMGU3NTU1YWQ2ZTM2NDQzZGZhMDc4MGMyYzQwMjMxZTkwYmU0ZjNlYzk5NTM5NTNiIiwidGFnIjoiIn0%3Dfpestid=lbwvGiXYriJVwA0g4i4Z5mNBVQ18k4lyIQO0xc9NQFqIW1_8-KR3YjdX9XGmJUZ0OicdEg; wayfindertarget=eyJpdiI6IlIwSDNLZUlPOTN0UUt5Q2hCNkJ5OUE9PSIsInZhbHVlIjoiMTQ3Tzdp" ] "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:4 [ "fpestid" => null "wayfindertarget" => null "XSRF-TOKEN" => "iJLcvEum1h9MAcWhqi2xHLsTgq7WoNTB8dHcMXjV" "alphaeurekaselectnet_session" => "hBSpNBBaU6E6YRzi8axP2rh6FSYg5dBF5jDllRuL" ]
        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 => "Mon, 17 Feb 2025 23:25:17 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6InVURjZ2MDBEUlRIbFVNSlBaN3RUOHc9PSIsInZhbHVlIjoic1hWOTlQaHZLOVVzMGdySDZYMUJvZDN5eUU3Tzhmb1ZXOVlxZTRmVUxsMHVEditQYWNnbzdSRVBuOGJzNVYyZnN0NlZKcmE0OHozeFIwUTVZK3p2WXdJNlpvZkY2T0xya3dNb1VQTjZ1czJ1NnVRMzY4MGt5RDZtUC96QURHRWsiLCJtYWMiOiJiMGExNWRmNmU2ZDk0MWJlMmEyODA3NzBlNTBiYTNkYmNjNTMyMjFlNWMzYmRlMmQ0ZDE1ZDQ3ZmU0NDc4NTI1IiwidGFnIjoiIn0%3D; expires=Thu, 20 Feb 2025 11:25:17 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6InVURjZ2MDBEUlRIbFVNSlBaN3RUOHc9PSIsInZhbHVlIjoic1hWOTlQaHZLOVVzMGdySDZYMUJvZDN5eUU3Tzhmb1ZXOVlxZTRmVUxsMHVEditQYWNnbzdSRVBuOGJzNVYyZnN0NlZKc" 1 => "alphaeurekaselectnet_session=eyJpdiI6InZMcG1MekFZS3NBYkVjMU5ab1ZyREE9PSIsInZhbHVlIjoidUlPZHRJVHJJUjdqb3htM1BRaEhKVTZRUEMvdzhEcmNiL2JjUTFMM21JbkhXYTM3TVl4WHMrSVFXQXQ4Skx0TUxQQWVtckt1bmZKbVBVZ2V2Q1ZQLzZQMUM3UkE4Mi9TdVA4bFd3MDQ2ZkFNQUc5dUJsMklOWDRaRVVRWGp3cEciLCJtYWMiOiJkYWRlYTViNzQxMzYxMzEzYzlhZWVjMjJhYjlkNzE4YmYwNzRjNjViMDM1MDEyNzQ5Y2I3Nzc5MzA2NGFkMDhjIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6InZMcG1MekFZS3NBYkVjMU5ab1ZyREE9PSIsInZhbHVlIjoidUlPZHRJVHJJUjdqb3htM1BRaEhKVTZRUEMvdzhEcmNiL2JjUTFMM21JbkhXYTM3TVl4WHMrSVF" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6InVURjZ2MDBEUlRIbFVNSlBaN3RUOHc9PSIsInZhbHVlIjoic1hWOTlQaHZLOVVzMGdySDZYMUJvZDN5eUU3Tzhmb1ZXOVlxZTRmVUxsMHVEditQYWNnbzdSRVBuOGJzNVYyZnN0NlZKcmE0OHozeFIwUTVZK3p2WXdJNlpvZkY2T0xya3dNb1VQTjZ1czJ1NnVRMzY4MGt5RDZtUC96QURHRWsiLCJtYWMiOiJiMGExNWRmNmU2ZDk0MWJlMmEyODA3NzBlNTBiYTNkYmNjNTMyMjFlNWMzYmRlMmQ0ZDE1ZDQ3ZmU0NDc4NTI1IiwidGFnIjoiIn0%3D; expires=Thu, 20-Feb-2025 11:25:17 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6InVURjZ2MDBEUlRIbFVNSlBaN3RUOHc9PSIsInZhbHVlIjoic1hWOTlQaHZLOVVzMGdySDZYMUJvZDN5eUU3Tzhmb1ZXOVlxZTRmVUxsMHVEditQYWNnbzdSRVBuOGJzNVYyZnN0NlZKc" 1 => "alphaeurekaselectnet_session=eyJpdiI6InZMcG1MekFZS3NBYkVjMU5ab1ZyREE9PSIsInZhbHVlIjoidUlPZHRJVHJJUjdqb3htM1BRaEhKVTZRUEMvdzhEcmNiL2JjUTFMM21JbkhXYTM3TVl4WHMrSVFXQXQ4Skx0TUxQQWVtckt1bmZKbVBVZ2V2Q1ZQLzZQMUM3UkE4Mi9TdVA4bFd3MDQ2ZkFNQUc5dUJsMklOWDRaRVVRWGp3cEciLCJtYWMiOiJkYWRlYTViNzQxMzYxMzEzYzlhZWVjMjJhYjlkNzE4YmYwNzRjNjViMDM1MDEyNzQ5Y2I3Nzc5MzA2NGFkMDhjIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6InZMcG1MekFZS3NBYkVjMU5ab1ZyREE9PSIsInZhbHVlIjoidUlPZHRJVHJJUjdqb3htM1BRaEhKVTZRUEMvdzhEcmNiL2JjUTFMM21JbkhXYTM3TVl4WHMrSVF" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "iJLcvEum1h9MAcWhqi2xHLsTgq7WoNTB8dHcMXjV" "uc_cart_id" => "0a4f6da223b447dedf7613234a58dc88" "_previous" => array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/6729" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-17 23:25:17GET/chapter/6729112193