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Filename: drivers/Session_files_driver.php
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Function: require_once
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Filename: Session/Session.php
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Function: require_once
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Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
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Function: _error_handler
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Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
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Function: _error_handler
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Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
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Function: require_once
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
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Function: _error_handler
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Filename: models/Detail_model.php
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Function: strpos
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Function: insertAPISummary
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Function: require_once
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Filename: helpers/my_audit_helper.php
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Function: formatAIDetailSummary
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Filename: controllers/Detail.php
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Backtrace:
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Line: 256
Function: _error_handler
File: /var/www/html/index.php
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Function: require_once
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 256
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 256
Function: _error_handler
File: /var/www/html/index.php
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Filename: controllers/Detail.php
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Function: _error_handler
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Filename: controllers/Detail.php
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Function: _error_handler
File: /var/www/html/index.php
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Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
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Function: _error_handler
File: /var/www/html/index.php
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Filename: controllers/Detail.php
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Function: _error_handler
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Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
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Function: _error_handler
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Function: _error_handler
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Message: file_get_contents(https://...@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
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Function: require_once
Complexes of cationic lipids and DNA (lipoplexes) are widely used for non-viral gene delivery and DNA vaccine development, but cationic lipids are toxic and promote non-specific interactions with cells, leading to poor efficacy. Near-neutral lipoplexes, on the other hand, can obviate toxicity, but a convenient means to target them to specific cells such as dendritic cells (DCs) has been lacking. Here, we show that a His-tagged flagellin-derived peptide (denoted 9Flg), previously reported to promote binding of liposomal antigen to TLR5-expressing cells, can be used to target near-neutral pDNA-lipoplexes incorporating the chelator lipid NTA(3)-DTDA (3(nitrilotriacetic acid)-ditetradecylamine) to DCs and other antigen-presenting cells (APCs). Thus, we show that pDNA-lipoplexes engrafted with 9Flg target pDNA to APCs in vitro and in vivo. Following i.v. administration, radiolabelled 9Flg-lipoplexes exhibited increased accumulation in spleen, lung and liver. Vaccination of C57BL/6 mice with 9Flg-lipoplexes containing either pcDNA3.1-SIIN (pSIIN) or a Kunjin virus replicon-based vector (pKUN), each encoding the epitope OVA(257-264) (SIINFEKL), induced Ag-specific T cell priming, and elicited strong cellular immunity as reflected by a marked increase in the number of Ag-responsive IFN-γ-producing CD8(+) T cells. Importantly, compared to i.m. injection of these SIINFEKL-encoding pDNAs in naked form, the i.v. administration of pSIIN or pKUN in 9Flg-lipoplexes to C57BL/6 mice induced a significantly more potent anti-tumour response in the B16-OVA melanoma tumour model. The targeting of near-neutral 9Flg-lipoplexes bearing pDNA encoding tumour antigens to TLR5 on APCs, therefore, is a powerful approach for developing more effective DNA vaccines and immunotherapies.
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Source |
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http://dx.doi.org/10.1016/j.vaccine.2011.07.045 | DOI Listing |
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