ATTENUATED STRAINS OF VIBRIO CHOLERAE WITH IMPROVED BIOLOGICAL SAFETY FEATURES IN FREEZE DRIED FORM FOR ORAL VACCINATION
The present invention discloses new live attenuated strains for oral immunization against cholera that are provided in freeze dried formulations for long term storage and administration to humans. These strains combine the two most important properties of live attenuated cholera vaccine candidates....
Gespeichert in:
| Hauptverfasser: | , , , , , , , , , , |
|---|---|
| Format: | Patent |
| Sprache: | eng ; fre |
| Schlagworte: | |
| Online-Zugang: | Volltext bestellen |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | |
| container_start_page | |
| container_title | |
| container_volume | |
| creator | MARRERO DOMINGUEZ, KAREN URRA VILLAVICENCIO, CARIDAD RODRIGUEZ GONZALEZ, BORIS LUIS SUZARTE PORTAL, EDITH MOREIRA HERNANDEZ, TOMAS MARCELINO SILVA LARRANAGA, YUSSUAN MARTINEZ GUTIERREZ, ERIEL LEDON PEREZ, TALENA YAMILE FANDO CALZADA, RAFAEL ALFREDO CAMPOS GOMEZ, JAVIER DELGADO RODRIGUEZ, HERMINIA DE LA CARIDAD |
| description | The present invention discloses new live attenuated strains for oral immunization against cholera that are provided in freeze dried formulations for long term storage and administration to humans. These strains combine the two most important properties of live attenuated cholera vaccine candidates. One such property is being well tolerated by people ingesting them. This was achieved by virtue of mutations already described in the art. The second property is having enhanced environmental safety due to the absence of VGJ.PHI. DNA in their genomes and also due to null mutations in the mshA gene or other spontaneous mutations conducive to the lack of MSHA type IV fimbria on the bacterial surface. This was done envisioning that VGJ.PHI. is a filamentous phage able to recombine with CTX.PHI. and disseminate the cholera toxin genes. This VGJ.PHI. phage as well as the VGJ.PHI.-CTX.PHI. recombinants uses the MSHA fibers as receptor. Being devoid of MSHA fimbria the vaccine candidates are protected from acquiring CTX.PHI. from the recombinant hybrid VGJ.PHI.-CTX.PHI.. Being devoid of VGJ.PHI., the vaccine candidates are impaired in the dissemination of CTX.PHI., via VGJ.PHI..
La présente invention concerne de nouvelles souches vivantes utilisées par voie orale pour immuniser un individu contre le choléra, lyophilisées en préparations permettant un stockage à long terme. Ces souches contiennent les deux propriétés les plus importantes que doivent posséder les candidats vaccinaux destinés à l'immunisation contre le choléra. Une de ces propriétés est définie par un niveau de réactogénicité réduit jusqu'à des niveaux acceptables, en raison de l'utilisation de mutations déjà connues et décrites dans les antériorités. L'autre propriété est définie par un meilleur indice de protection environnementale en raison de la suppression du gène mshA ou de mutations spontanées conduisant à l'absence du pilus MSHA sur la surface externe de la bactérie et à l'absence du phage VGJ.PHI. dans sa dotation génétique qui, s'ils étaient présents, permettraient l'introduction et la dissémination du phage CTX.PHI. assistée par VGJ.PHI.. |
| format | Patent |
| fullrecord | <record><control><sourceid>epo_EVB</sourceid><recordid>TN_cdi_epo_espacenet_CA2516581C</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>CA2516581C</sourcerecordid><originalsourceid>FETCH-epo_espacenet_CA2516581C3</originalsourceid><addsrcrecordid>eNqFzDEKwkAQheE0FqKewbmARZSI7WQzawbijkw2EW1CkLUSDcTC47uCvc37m483Td7oPbkGPRVQe0V2NYiFlnNlAVNKRYoEJ_Yl8OGo0kaYs1SyZ4MV1GjJn8ES-kapBnZglehCUChHakUP3wHRqFs0hh16FjdPJrf-PobFr7NkGZ9MuQrDswvj0F_DI7w6g-ss3Wa71Gz-iw-66zkN</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>patent</recordtype></control><display><type>patent</type><title>ATTENUATED STRAINS OF VIBRIO CHOLERAE WITH IMPROVED BIOLOGICAL SAFETY FEATURES IN FREEZE DRIED FORM FOR ORAL VACCINATION</title><source>esp@cenet</source><creator>MARRERO DOMINGUEZ, KAREN ; URRA VILLAVICENCIO, CARIDAD ; RODRIGUEZ GONZALEZ, BORIS LUIS ; SUZARTE PORTAL, EDITH ; MOREIRA HERNANDEZ, TOMAS MARCELINO ; SILVA LARRANAGA, YUSSUAN ; MARTINEZ GUTIERREZ, ERIEL ; LEDON PEREZ, TALENA YAMILE ; FANDO CALZADA, RAFAEL ALFREDO ; CAMPOS GOMEZ, JAVIER ; DELGADO RODRIGUEZ, HERMINIA DE LA CARIDAD</creator><creatorcontrib>MARRERO DOMINGUEZ, KAREN ; URRA VILLAVICENCIO, CARIDAD ; RODRIGUEZ GONZALEZ, BORIS LUIS ; SUZARTE PORTAL, EDITH ; MOREIRA HERNANDEZ, TOMAS MARCELINO ; SILVA LARRANAGA, YUSSUAN ; MARTINEZ GUTIERREZ, ERIEL ; LEDON PEREZ, TALENA YAMILE ; FANDO CALZADA, RAFAEL ALFREDO ; CAMPOS GOMEZ, JAVIER ; DELGADO RODRIGUEZ, HERMINIA DE LA CARIDAD</creatorcontrib><description>The present invention discloses new live attenuated strains for oral immunization against cholera that are provided in freeze dried formulations for long term storage and administration to humans. These strains combine the two most important properties of live attenuated cholera vaccine candidates. One such property is being well tolerated by people ingesting them. This was achieved by virtue of mutations already described in the art. The second property is having enhanced environmental safety due to the absence of VGJ.PHI. DNA in their genomes and also due to null mutations in the mshA gene or other spontaneous mutations conducive to the lack of MSHA type IV fimbria on the bacterial surface. This was done envisioning that VGJ.PHI. is a filamentous phage able to recombine with CTX.PHI. and disseminate the cholera toxin genes. This VGJ.PHI. phage as well as the VGJ.PHI.-CTX.PHI. recombinants uses the MSHA fibers as receptor. Being devoid of MSHA fimbria the vaccine candidates are protected from acquiring CTX.PHI. from the recombinant hybrid VGJ.PHI.-CTX.PHI.. Being devoid of VGJ.PHI., the vaccine candidates are impaired in the dissemination of CTX.PHI., via VGJ.PHI..
La présente invention concerne de nouvelles souches vivantes utilisées par voie orale pour immuniser un individu contre le choléra, lyophilisées en préparations permettant un stockage à long terme. Ces souches contiennent les deux propriétés les plus importantes que doivent posséder les candidats vaccinaux destinés à l'immunisation contre le choléra. Une de ces propriétés est définie par un niveau de réactogénicité réduit jusqu'à des niveaux acceptables, en raison de l'utilisation de mutations déjà connues et décrites dans les antériorités. L'autre propriété est définie par un meilleur indice de protection environnementale en raison de la suppression du gène mshA ou de mutations spontanées conduisant à l'absence du pilus MSHA sur la surface externe de la bactérie et à l'absence du phage VGJ.PHI. dans sa dotation génétique qui, s'ils étaient présents, permettraient l'introduction et la dissémination du phage CTX.PHI. assistée par VGJ.PHI..</description><language>eng ; fre</language><subject>BEER ; BIOCHEMISTRY ; CHEMISTRY ; COMPOSITIONS THEREOF ; CULTURE MEDIA ; ENZYMOLOGY ; HUMAN NECESSITIES ; HYGIENE ; MEASURING ; MEDICAL OR VETERINARY SCIENCE ; METALLURGY ; MICROBIOLOGY ; MICROORGANISMS OR ENZYMES ; MUTATION OR GENETIC ENGINEERING ; ORGANIC CHEMISTRY ; PEPTIDES ; PHYSICS ; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES ; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS ; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS ; SPIRITS ; TESTING ; TESTING STATIC OR DYNAMIC BALANCE OF MACHINES ORSTRUCTURES ; TESTING STRUCTURES OR APPARATUS NOT OTHERWISE PROVIDED FOR ; VINEGAR ; WINE</subject><creationdate>2012</creationdate><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://worldwide.espacenet.com/publicationDetails/biblio?FT=D&date=20120515&DB=EPODOC&CC=CA&NR=2516581C$$EHTML$$P50$$Gepo$$Hfree_for_read</linktohtml><link.rule.ids>230,308,780,885,25564,76547</link.rule.ids><linktorsrc>$$Uhttps://worldwide.espacenet.com/publicationDetails/biblio?FT=D&date=20120515&DB=EPODOC&CC=CA&NR=2516581C$$EView_record_in_European_Patent_Office$$FView_record_in_$$GEuropean_Patent_Office$$Hfree_for_read</linktorsrc></links><search><creatorcontrib>MARRERO DOMINGUEZ, KAREN</creatorcontrib><creatorcontrib>URRA VILLAVICENCIO, CARIDAD</creatorcontrib><creatorcontrib>RODRIGUEZ GONZALEZ, BORIS LUIS</creatorcontrib><creatorcontrib>SUZARTE PORTAL, EDITH</creatorcontrib><creatorcontrib>MOREIRA HERNANDEZ, TOMAS MARCELINO</creatorcontrib><creatorcontrib>SILVA LARRANAGA, YUSSUAN</creatorcontrib><creatorcontrib>MARTINEZ GUTIERREZ, ERIEL</creatorcontrib><creatorcontrib>LEDON PEREZ, TALENA YAMILE</creatorcontrib><creatorcontrib>FANDO CALZADA, RAFAEL ALFREDO</creatorcontrib><creatorcontrib>CAMPOS GOMEZ, JAVIER</creatorcontrib><creatorcontrib>DELGADO RODRIGUEZ, HERMINIA DE LA CARIDAD</creatorcontrib><title>ATTENUATED STRAINS OF VIBRIO CHOLERAE WITH IMPROVED BIOLOGICAL SAFETY FEATURES IN FREEZE DRIED FORM FOR ORAL VACCINATION</title><description>The present invention discloses new live attenuated strains for oral immunization against cholera that are provided in freeze dried formulations for long term storage and administration to humans. These strains combine the two most important properties of live attenuated cholera vaccine candidates. One such property is being well tolerated by people ingesting them. This was achieved by virtue of mutations already described in the art. The second property is having enhanced environmental safety due to the absence of VGJ.PHI. DNA in their genomes and also due to null mutations in the mshA gene or other spontaneous mutations conducive to the lack of MSHA type IV fimbria on the bacterial surface. This was done envisioning that VGJ.PHI. is a filamentous phage able to recombine with CTX.PHI. and disseminate the cholera toxin genes. This VGJ.PHI. phage as well as the VGJ.PHI.-CTX.PHI. recombinants uses the MSHA fibers as receptor. Being devoid of MSHA fimbria the vaccine candidates are protected from acquiring CTX.PHI. from the recombinant hybrid VGJ.PHI.-CTX.PHI.. Being devoid of VGJ.PHI., the vaccine candidates are impaired in the dissemination of CTX.PHI., via VGJ.PHI..
La présente invention concerne de nouvelles souches vivantes utilisées par voie orale pour immuniser un individu contre le choléra, lyophilisées en préparations permettant un stockage à long terme. Ces souches contiennent les deux propriétés les plus importantes que doivent posséder les candidats vaccinaux destinés à l'immunisation contre le choléra. Une de ces propriétés est définie par un niveau de réactogénicité réduit jusqu'à des niveaux acceptables, en raison de l'utilisation de mutations déjà connues et décrites dans les antériorités. L'autre propriété est définie par un meilleur indice de protection environnementale en raison de la suppression du gène mshA ou de mutations spontanées conduisant à l'absence du pilus MSHA sur la surface externe de la bactérie et à l'absence du phage VGJ.PHI. dans sa dotation génétique qui, s'ils étaient présents, permettraient l'introduction et la dissémination du phage CTX.PHI. assistée par VGJ.PHI..</description><subject>BEER</subject><subject>BIOCHEMISTRY</subject><subject>CHEMISTRY</subject><subject>COMPOSITIONS THEREOF</subject><subject>CULTURE MEDIA</subject><subject>ENZYMOLOGY</subject><subject>HUMAN NECESSITIES</subject><subject>HYGIENE</subject><subject>MEASURING</subject><subject>MEDICAL OR VETERINARY SCIENCE</subject><subject>METALLURGY</subject><subject>MICROBIOLOGY</subject><subject>MICROORGANISMS OR ENZYMES</subject><subject>MUTATION OR GENETIC ENGINEERING</subject><subject>ORGANIC CHEMISTRY</subject><subject>PEPTIDES</subject><subject>PHYSICS</subject><subject>PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES</subject><subject>PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS</subject><subject>SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS</subject><subject>SPIRITS</subject><subject>TESTING</subject><subject>TESTING STATIC OR DYNAMIC BALANCE OF MACHINES ORSTRUCTURES</subject><subject>TESTING STRUCTURES OR APPARATUS NOT OTHERWISE PROVIDED FOR</subject><subject>VINEGAR</subject><subject>WINE</subject><fulltext>true</fulltext><rsrctype>patent</rsrctype><creationdate>2012</creationdate><recordtype>patent</recordtype><sourceid>EVB</sourceid><recordid>eNqFzDEKwkAQheE0FqKewbmARZSI7WQzawbijkw2EW1CkLUSDcTC47uCvc37m483Td7oPbkGPRVQe0V2NYiFlnNlAVNKRYoEJ_Yl8OGo0kaYs1SyZ4MV1GjJn8ES-kapBnZglehCUChHakUP3wHRqFs0hh16FjdPJrf-PobFr7NkGZ9MuQrDswvj0F_DI7w6g-ss3Wa71Gz-iw-66zkN</recordid><startdate>20120515</startdate><enddate>20120515</enddate><creator>MARRERO DOMINGUEZ, KAREN</creator><creator>URRA VILLAVICENCIO, CARIDAD</creator><creator>RODRIGUEZ GONZALEZ, BORIS LUIS</creator><creator>SUZARTE PORTAL, EDITH</creator><creator>MOREIRA HERNANDEZ, TOMAS MARCELINO</creator><creator>SILVA LARRANAGA, YUSSUAN</creator><creator>MARTINEZ GUTIERREZ, ERIEL</creator><creator>LEDON PEREZ, TALENA YAMILE</creator><creator>FANDO CALZADA, RAFAEL ALFREDO</creator><creator>CAMPOS GOMEZ, JAVIER</creator><creator>DELGADO RODRIGUEZ, HERMINIA DE LA CARIDAD</creator><scope>EVB</scope></search><sort><creationdate>20120515</creationdate><title>ATTENUATED STRAINS OF VIBRIO CHOLERAE WITH IMPROVED BIOLOGICAL SAFETY FEATURES IN FREEZE DRIED FORM FOR ORAL VACCINATION</title><author>MARRERO DOMINGUEZ, KAREN ; URRA VILLAVICENCIO, CARIDAD ; RODRIGUEZ GONZALEZ, BORIS LUIS ; SUZARTE PORTAL, EDITH ; MOREIRA HERNANDEZ, TOMAS MARCELINO ; SILVA LARRANAGA, YUSSUAN ; MARTINEZ GUTIERREZ, ERIEL ; LEDON PEREZ, TALENA YAMILE ; FANDO CALZADA, RAFAEL ALFREDO ; CAMPOS GOMEZ, JAVIER ; DELGADO RODRIGUEZ, HERMINIA DE LA CARIDAD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-epo_espacenet_CA2516581C3</frbrgroupid><rsrctype>patents</rsrctype><prefilter>patents</prefilter><language>eng ; fre</language><creationdate>2012</creationdate><topic>BEER</topic><topic>BIOCHEMISTRY</topic><topic>CHEMISTRY</topic><topic>COMPOSITIONS THEREOF</topic><topic>CULTURE MEDIA</topic><topic>ENZYMOLOGY</topic><topic>HUMAN NECESSITIES</topic><topic>HYGIENE</topic><topic>MEASURING</topic><topic>MEDICAL OR VETERINARY SCIENCE</topic><topic>METALLURGY</topic><topic>MICROBIOLOGY</topic><topic>MICROORGANISMS OR ENZYMES</topic><topic>MUTATION OR GENETIC ENGINEERING</topic><topic>ORGANIC CHEMISTRY</topic><topic>PEPTIDES</topic><topic>PHYSICS</topic><topic>PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES</topic><topic>PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS</topic><topic>SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS</topic><topic>SPIRITS</topic><topic>TESTING</topic><topic>TESTING STATIC OR DYNAMIC BALANCE OF MACHINES ORSTRUCTURES</topic><topic>TESTING STRUCTURES OR APPARATUS NOT OTHERWISE PROVIDED FOR</topic><topic>VINEGAR</topic><topic>WINE</topic><toplevel>online_resources</toplevel><creatorcontrib>MARRERO DOMINGUEZ, KAREN</creatorcontrib><creatorcontrib>URRA VILLAVICENCIO, CARIDAD</creatorcontrib><creatorcontrib>RODRIGUEZ GONZALEZ, BORIS LUIS</creatorcontrib><creatorcontrib>SUZARTE PORTAL, EDITH</creatorcontrib><creatorcontrib>MOREIRA HERNANDEZ, TOMAS MARCELINO</creatorcontrib><creatorcontrib>SILVA LARRANAGA, YUSSUAN</creatorcontrib><creatorcontrib>MARTINEZ GUTIERREZ, ERIEL</creatorcontrib><creatorcontrib>LEDON PEREZ, TALENA YAMILE</creatorcontrib><creatorcontrib>FANDO CALZADA, RAFAEL ALFREDO</creatorcontrib><creatorcontrib>CAMPOS GOMEZ, JAVIER</creatorcontrib><creatorcontrib>DELGADO RODRIGUEZ, HERMINIA DE LA CARIDAD</creatorcontrib><collection>esp@cenet</collection></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>MARRERO DOMINGUEZ, KAREN</au><au>URRA VILLAVICENCIO, CARIDAD</au><au>RODRIGUEZ GONZALEZ, BORIS LUIS</au><au>SUZARTE PORTAL, EDITH</au><au>MOREIRA HERNANDEZ, TOMAS MARCELINO</au><au>SILVA LARRANAGA, YUSSUAN</au><au>MARTINEZ GUTIERREZ, ERIEL</au><au>LEDON PEREZ, TALENA YAMILE</au><au>FANDO CALZADA, RAFAEL ALFREDO</au><au>CAMPOS GOMEZ, JAVIER</au><au>DELGADO RODRIGUEZ, HERMINIA DE LA CARIDAD</au><format>patent</format><genre>patent</genre><ristype>GEN</ristype><title>ATTENUATED STRAINS OF VIBRIO CHOLERAE WITH IMPROVED BIOLOGICAL SAFETY FEATURES IN FREEZE DRIED FORM FOR ORAL VACCINATION</title><date>2012-05-15</date><risdate>2012</risdate><abstract>The present invention discloses new live attenuated strains for oral immunization against cholera that are provided in freeze dried formulations for long term storage and administration to humans. These strains combine the two most important properties of live attenuated cholera vaccine candidates. One such property is being well tolerated by people ingesting them. This was achieved by virtue of mutations already described in the art. The second property is having enhanced environmental safety due to the absence of VGJ.PHI. DNA in their genomes and also due to null mutations in the mshA gene or other spontaneous mutations conducive to the lack of MSHA type IV fimbria on the bacterial surface. This was done envisioning that VGJ.PHI. is a filamentous phage able to recombine with CTX.PHI. and disseminate the cholera toxin genes. This VGJ.PHI. phage as well as the VGJ.PHI.-CTX.PHI. recombinants uses the MSHA fibers as receptor. Being devoid of MSHA fimbria the vaccine candidates are protected from acquiring CTX.PHI. from the recombinant hybrid VGJ.PHI.-CTX.PHI.. Being devoid of VGJ.PHI., the vaccine candidates are impaired in the dissemination of CTX.PHI., via VGJ.PHI..
La présente invention concerne de nouvelles souches vivantes utilisées par voie orale pour immuniser un individu contre le choléra, lyophilisées en préparations permettant un stockage à long terme. Ces souches contiennent les deux propriétés les plus importantes que doivent posséder les candidats vaccinaux destinés à l'immunisation contre le choléra. Une de ces propriétés est définie par un niveau de réactogénicité réduit jusqu'à des niveaux acceptables, en raison de l'utilisation de mutations déjà connues et décrites dans les antériorités. L'autre propriété est définie par un meilleur indice de protection environnementale en raison de la suppression du gène mshA ou de mutations spontanées conduisant à l'absence du pilus MSHA sur la surface externe de la bactérie et à l'absence du phage VGJ.PHI. dans sa dotation génétique qui, s'ils étaient présents, permettraient l'introduction et la dissémination du phage CTX.PHI. assistée par VGJ.PHI..</abstract><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext_linktorsrc |
| identifier | |
| ispartof | |
| issn | |
| language | eng ; fre |
| recordid | cdi_epo_espacenet_CA2516581C |
| source | esp@cenet |
| subjects | BEER BIOCHEMISTRY CHEMISTRY COMPOSITIONS THEREOF CULTURE MEDIA ENZYMOLOGY HUMAN NECESSITIES HYGIENE MEASURING MEDICAL OR VETERINARY SCIENCE METALLURGY MICROBIOLOGY MICROORGANISMS OR ENZYMES MUTATION OR GENETIC ENGINEERING ORGANIC CHEMISTRY PEPTIDES PHYSICS PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS SPIRITS TESTING TESTING STATIC OR DYNAMIC BALANCE OF MACHINES ORSTRUCTURES TESTING STRUCTURES OR APPARATUS NOT OTHERWISE PROVIDED FOR VINEGAR WINE |
| title | ATTENUATED STRAINS OF VIBRIO CHOLERAE WITH IMPROVED BIOLOGICAL SAFETY FEATURES IN FREEZE DRIED FORM FOR ORAL VACCINATION |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-19T13%3A42%3A18IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-epo_EVB&rft_val_fmt=info:ofi/fmt:kev:mtx:patent&rft.genre=patent&rft.au=MARRERO%20DOMINGUEZ,%20KAREN&rft.date=2012-05-15&rft_id=info:doi/&rft_dat=%3Cepo_EVB%3ECA2516581C%3C/epo_EVB%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/&rfr_iscdi=true |