WorldWideScience

Sample records for service cas registry

  1. Facility Registry Service (FRS)

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Facility Registry Service (FRS) provides an integrated source of comprehensive (air, water, and waste) environmental information about facilities across EPA,...

  2. Data Element Registry Services

    Data.gov (United States)

    U.S. Environmental Protection Agency — Data Element Registry Services (DERS) is a resource for information about value lists (aka code sets / pick lists), data dictionaries, data elements, and EPA data...

  3. Tenth anniversary of CAS ONLINE service : What CAS services should be in the new era of chemical information

    Science.gov (United States)

    Kostakos, Charles N.

    Chemical Abstracts Service celebrated 10th anniversary of CAS online information service in 1990. A speech given on the occasion reviewed history of the CAS ONLINE, in relation to its most important benefits for scientists and engineers. The development of STN international, the network through which CAS ONLINE is accessible around the world, was also discussed in the speech. The CAS ONLINE now contains a wide variety of files relating to chemical field including CA file, Registry file. CA previews,. CASREACT, CIN. MARPAT, etc for supplying chemical information worldwide.

  4. Service registry design: an information service approach

    NARCIS (Netherlands)

    Ferreira Pires, Luis; Wang, J.; van Oostrum, Arjen; Wijnhoven, Alphonsus B.J.M.

    2010-01-01

    A service registry is a Service-Oriented Architecture (SOA) component that keeps a ‘catalogue’ of available services. It stores service specifications so that these specifications can be found by potential users. Discussions on the design of service registries currently focus on technical issues,

  5. Environmental Agents Service (EAS) Registry System of Records

    Data.gov (United States)

    Department of Veterans Affairs — The Environmental Agent Service (EAS) Registries is the information system encompassing the Ionizing Radiation Registry (IRR), the Agent Orange Registry (AOR), and...

  6. EPA Facility Registry Service (FRS): RADINFO

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web feature service contains location and facility identification information from EPA's Facility Registry Service (FRS) for the subset of facilities that link...

  7. EPA Facility Registry Service (FRS): NEI

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web feature service contains location and facility identification information from EPA's Facility Registry Service (FRS) for the subset of facilities that link...

  8. EPA Facility Registry Service (FRS): BIA

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web feature service contains location and facility identification information from EPA's Facility Registry Service (FRS) for the subset of facilities that link...

  9. EPA Facility Registry Service (FRS): BRAC

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web feature service contains location and facility identification information from EPA's Facility Registry Service (FRS) for the subset of facilities that link...

  10. EPA Facility Registry Service (FRS): NCDB

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web feature service contains location and facility identification information from EPA's Facility Registry Service (FRS) for the subset of facilities that link...

  11. EPA Facility Registry Service (FRS): TRI

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web feature service contains location and facility identification information from EPA's Facility Registry Service (FRS) for the subset of facilities that link...

  12. EPA Facility Registry Service (FRS): ICIS

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web feature service contains location and facility identification information from EPA's Facility Registry Service (FRS) for the subset of facilities that link...

  13. EPA Facility Registry Service (FRS): RBLC

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web feature service contains location and facility identification information from EPA's Facility Registry Service (FRS) for the subset of facilities that link...

  14. EPA Facility Registry Service (FRS): ACRES

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web feature service consists of location and facility identification information from EPA's Facility Registry Service (FRS) for the subset of sites that link to...

  15. EPA Facility Registry Service (FRS): LANDFILL

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web feature service contains location and facility identification information from EPA's Facility Registry Service (FRS) for the subset of non-hazardous waste...

  16. EPA Facility Registry Service (FRS): CAMDBS

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web feature service contains location and facility identification information from EPA's Facility Registry Service (FRS) for the subset of facilities that link...

  17. EPA Facility Registry Service (FRS): SDWIS

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web feature service contains location and facility identification information from EPA's Facility Registry Service (FRS) for the subset of facilities that link...

  18. EPA Facility Registry Service (FRS): RCRA

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web feature service contains location and facility identification information from EPA's Facility Registry Service (FRS) for the subset of hazardous waste...

  19. EPA Facility Registry Service (FRS): RMP

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web feature service contains location and facility identification information from EPA's Facility Registry Service (FRS) for the subset of facilities that link...

  20. EPA Linked Open Data: Facility Registry Service

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Facility Registry Service (FRS) identifies facilities, sites, or places subject to environmental regulation or of environmental interest to EPA programs or...

  1. EPA Facility Registry Service (FRS): OIL

    Data.gov (United States)

    U.S. Environmental Protection Agency — This dataset contains location and facility identification information from EPA's Facility Registry Service (FRS) for the subset of facilities that link to the Oil...

  2. EPA Linked Open Data: Substance Registry Service

    Data.gov (United States)

    U.S. Environmental Protection Agency — Substance Registry Services (SRS) is the Environmental Protection Agency's (EPA) central system for information about substances that are tracked or regulated by EPA...

  3. An active registry for bioinformatics web services.

    NARCIS (Netherlands)

    Pettifer, S.; Thorne, D.; McDermott, P.; Attwood, T.; Baran, J.; Bryne, J.C.; Hupponen, T.; Mowbray, D.; Vriend, G.

    2009-01-01

    SUMMARY: The EMBRACE Registry is a web portal that collects and monitors web services according to test scripts provided by the their administrators. Users are able to search for, rank and annotate services, enabling them to select the most appropriate working service for inclusion in their

  4. SOA - Service Registry and Repository

    Data.gov (United States)

    Social Security Administration — SOA is an approach utilizing reusable components or services in order to build applications by plugging in the appropriate components. It utilizes COTS databases as...

  5. The GEOSS Component and Service Registry

    Science.gov (United States)

    Di, L.; Bai, Y.; Shen, D.; Shao, Y.; Shrestha, R.; Wang, H.; Nebert, D. D.

    2011-12-01

    Petabytes of Earth science data have been accumulated through space- and air-borne Earth observation programs during the last several decades. The data are valuable both scientifically and socioeconomically. The value of these data could be further increased significantly if the data from these programs can be easily discovered, accessed, integrated, and analyzed. The Global Earth Observation System of Systems (GEOSS) is addressing this need. Coordinated by the Group on Earth Observations (or GEO), a voluntary partnership of 86 governments, the European Commission, and 61 intergovernmental, international, and regional organizations has been working on implementing GEOSS for a number of years. After four years of international collaboration, the GEOSS Common Infrastructure (GCI) has been established. GCI consists of the Standards and Interoperability Registry (SIR), the Component and Service Registry (CSR), the GEO clearinghouse, and the GEO Portal. The SIR maintains the list of the public standards recognized by the GEO. CSR provides a centralized registry for available Earth Observation resources. The GEO clearinghouse works as a single search facility for GEOSS-wide resources and the GEO Portal provides an integrated Web-based interfaces for users. Since January 2007, researchers at CSISS, GMU have collaborated with officials from the Federal Geographic Data Committee (FGDC) on designing, implementing, maintaining, and upgrading CSR. Currently CSR provides the following capabilities for data providers: user registration, resource registration, and service interface registration. The CSR clients can discover the resources registered in CSR through OGC Catalog for Web (CSW), UUDI, and other standard interfaces. During the resource registration process, providers may define detailed descriptive information for their resources, in particular, the targeted societal benefit area and sub-areas of focus, and the targeted critical Earth Observations. The service

  6. Functional principles of registry-based service discovery

    NARCIS (Netherlands)

    Sundramoorthy, V.; Tan, C.; Hartel, P.H.; Hartog, den J.I.; Scholten, J.

    2005-01-01

    As Service Discovery Protocols (SDP) are becoming increasingly important for ubiquitous computing, they must behave according to predefined principles. We present the functional Principles of Service Discovery for robust, registry-based service discovery. A methodology to guarantee adherence to

  7. EPA Facility Registry Service (FRS): RCRA_INACTIVE

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web feature service contains location and facility identification information from EPA's Facility Registry Service (FRS) for the subset of hazardous waste...

  8. EPA Facility Registry Service (FRS): Facility Interests Dataset - Intranet

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web feature service consists of location and facility identification information from EPA's Facility Registry Service (FRS) for all sites that are available in...

  9. EPA Facility Registry Service (FRS): ALL FRS INTERESTS LAYER

    Data.gov (United States)

    U.S. Environmental Protection Agency — This data provides location and attribute information on all facilities in EPA's Facility Registry Service (FRS) for a internet web feature service . The FRS is an...

  10. EPA Facility Registry Service (FRS): AIRS_AQS

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web feature service contains location and facility identification information from EPA's Facility Registry Service (FRS) for the subset of facilities that link...

  11. EPA Facility Registry Service (FRS): Facility Interests Dataset

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web feature service consists of location and facility identification information from EPA's Facility Registry Service (FRS) for all sites that are available in...

  12. EPA Facility Registry Service (FRS): RCRA_ACTIVE

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web feature service contains location and facility identification information from EPA's Facility Registry Service (FRS) for the subset of active hazardous...

  13. EPA Facility Registry Service (FRS): RCRA_LQG

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web feature service contains location and facility identification information from EPA's Facility Registry Service (FRS) for the subset of facilities that link...

  14. EPA Facility Registry Service (FRS): AIRS_AFS

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web feature service contains location and facility identification information from EPA's Facility Registry Service (FRS) for the subset of facilities that link...

  15. EPA Facility Registry Service (FRS): RCRA_TRANS

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web feature service contains location and facility identification information from EPA's Facility Registry Service (FRS) for the subset of facilities that link...

  16. EPA Facility Registry Service (FRS): RCRA_TSD

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web feature service contains location and facility identification information from EPA's Facility Registry Service (FRS) for the subset of Hazardous Waste...

  17. EPA Facility Registry Service (FRS): CERCLIS_NPL

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web feature service contains location and facility identification information from EPA's Facility Registry Service (FRS) for the subset of facilities that are...

  18. EPA Facility Registry Service (FRS): PCS_NPDES_MAJOR

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web feature service contains location and facility identification information from EPA's Facility Registry Service (FRS) for the subset of facilities that are...

  19. EPA Facility Registry Service (FRS): PCS_NPDES

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web feature service contains location and facility identification information from EPA's Facility Registry Service (FRS) for the subset of facilities that link...

  20. EPA Facility Registry Service (FRS): Facility Interests Dataset - Intranet Download

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web feature service consists of location and facility identification information from EPA's Facility Registry Service (FRS) for all sites that are available in...

  1. EPA Facility Registry Service (FRS): AIRS_AFS_MAJOR

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web feature service contains location and facility identification information from EPA's Facility Registry Service (FRS) for the subset of facilities that link...

  2. EPA Facility Registry Service (FRS): Facility Interests Dataset - Intranet Download

    Data.gov (United States)

    U.S. Environmental Protection Agency — This downloadable data package consists of location and facility identification information from EPA's Facility Registry Service (FRS) for all sites that are...

  3. EPA Facility Registry Service (FRS): ER_EPLAN

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web feature service contains location and facility identification information from EPA's Facility Registry System (FRS) for the subset of facilities that link...

  4. EPA Facility Registry Service (FRS): Facility Interests Dataset Download

    Data.gov (United States)

    U.S. Environmental Protection Agency — This downloadable data package consists of location and facility identification information from EPA's Facility Registry Service (FRS) for all sites that are...

  5. EPA Facility Registry Service (FRS): ER_TRI

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web feature service contains location and facility identification information from EPA's Facility Registry System (FRS) for the subset of facilities that link...

  6. EPA Facility Registry Service (FRS): ER_TSCA

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web feature service contains location and facility identification information from EPA's Facility Registry System (FRS) for the subset of facilities that link...

  7. EPA Facility Registry Service (FRS): Wastewater Treatment Plants

    Data.gov (United States)

    U.S. Environmental Protection Agency — This GIS dataset contains data on wastewater treatment plants, based on EPA's Facility Registry Service (FRS), EPA's Integrated Compliance Information System (ICIS)...

  8. EPA Facility Registry Service (FRS): ER_WWTP_NPDES

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web feature service contains location and facility identification information from EPA's Facility Registry System (FRS) for the subset of Waste Water Treatment...

  9. EPA Facility Registry Service (FRS): ER_CERCLIS

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web feature service contains location and facility identification information from EPA's Facility Registry System (FRS) for the subset of facilities that link...

  10. EPA Facility Registry Service (FRS): ER_RMP

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web feature service contains location and facility identification information from EPA's Facility Registry System (FRS) for the subset of facilities that link...

  11. EPA Facility Registry Service (FRS): ER_RCRATSD

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web feature service contains location and facility identification information from EPA's Facility Registry System (FRS) for the subset of facilities that link...

  12. Environmental Protection Agency (EPA) Facility Registry Service (FRS) Power Plants

    Data.gov (United States)

    Department of Homeland Security — This GIS dataset contains data on wastewater treatment plants, based on EPA's Facility Registry Service (FRS) and NPDES, along with Clean Watersheds Needs Survey...

  13. BioSWR--semantic web services registry for bioinformatics.

    Directory of Open Access Journals (Sweden)

    Dmitry Repchevsky

    Full Text Available Despite of the variety of available Web services registries specially aimed at Life Sciences, their scope is usually restricted to a limited set of well-defined types of services. While dedicated registries are generally tied to a particular format, general-purpose ones are more adherent to standards and usually rely on Web Service Definition Language (WSDL. Although WSDL is quite flexible to support common Web services types, its lack of semantic expressiveness led to various initiatives to describe Web services via ontology languages. Nevertheless, WSDL 2.0 descriptions gained a standard representation based on Web Ontology Language (OWL. BioSWR is a novel Web services registry that provides standard Resource Description Framework (RDF based Web services descriptions along with the traditional WSDL based ones. The registry provides Web-based interface for Web services registration, querying and annotation, and is also accessible programmatically via Representational State Transfer (REST API or using a SPARQL Protocol and RDF Query Language. BioSWR server is located at http://inb.bsc.es/BioSWR/and its code is available at https://sourceforge.net/projects/bioswr/under the LGPL license.

  14. BioSWR – Semantic Web Services Registry for Bioinformatics

    Science.gov (United States)

    Repchevsky, Dmitry; Gelpi, Josep Ll.

    2014-01-01

    Despite of the variety of available Web services registries specially aimed at Life Sciences, their scope is usually restricted to a limited set of well-defined types of services. While dedicated registries are generally tied to a particular format, general-purpose ones are more adherent to standards and usually rely on Web Service Definition Language (WSDL). Although WSDL is quite flexible to support common Web services types, its lack of semantic expressiveness led to various initiatives to describe Web services via ontology languages. Nevertheless, WSDL 2.0 descriptions gained a standard representation based on Web Ontology Language (OWL). BioSWR is a novel Web services registry that provides standard Resource Description Framework (RDF) based Web services descriptions along with the traditional WSDL based ones. The registry provides Web-based interface for Web services registration, querying and annotation, and is also accessible programmatically via Representational State Transfer (REST) API or using a SPARQL Protocol and RDF Query Language. BioSWR server is located at http://inb.bsc.es/BioSWR/and its code is available at https://sourceforge.net/projects/bioswr/under the LGPL license. PMID:25233118

  15. BioSWR--semantic web services registry for bioinformatics.

    Science.gov (United States)

    Repchevsky, Dmitry; Gelpi, Josep Ll

    2014-01-01

    Despite of the variety of available Web services registries specially aimed at Life Sciences, their scope is usually restricted to a limited set of well-defined types of services. While dedicated registries are generally tied to a particular format, general-purpose ones are more adherent to standards and usually rely on Web Service Definition Language (WSDL). Although WSDL is quite flexible to support common Web services types, its lack of semantic expressiveness led to various initiatives to describe Web services via ontology languages. Nevertheless, WSDL 2.0 descriptions gained a standard representation based on Web Ontology Language (OWL). BioSWR is a novel Web services registry that provides standard Resource Description Framework (RDF) based Web services descriptions along with the traditional WSDL based ones. The registry provides Web-based interface for Web services registration, querying and annotation, and is also accessible programmatically via Representational State Transfer (REST) API or using a SPARQL Protocol and RDF Query Language. BioSWR server is located at http://inb.bsc.es/BioSWR/and its code is available at https://sourceforge.net/projects/bioswr/under the LGPL license.

  16. RIFM fragrance ingredient safety assessment, isobornyl isovalerate, CAS registry number 7779-73-9.

    Science.gov (United States)

    Api, A M; Belsito, D; Bhatia, S; Bruze, M; Calow, P; Dagli, M L; Dekant, W; Fryer, A D; Kromidas, L; La Cava, S; Lapczynski, A; Liebler, D C; O'Brien, D; Parakhia, R; Penning, T M; Politano, V T; Ritacco, G; Salvito, D; Schultz, T W; Shen, J; Sipes, I G; Wall, B; Wilcox, D K

    2017-12-01

    This material was evaluated for genotoxicity, repeated dose toxicity, developmental toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization potential, as well as, environmental safety. Data from the suitable read across analog isobornyl acetate (CAS # 125-12-2) show that this material is not genotoxic, provided a MOE > 100 for the repeated dose, developmental and reproductive endpoints, and does not have skin sensitization potential. The local respiratory toxicity endpoint was completed using the TTC (threshold of Toxicological Concern) for a Cramer Class II material (0.47 mg/day). The phototoxicity/photoallergenicity endpoint was completed based on suitable UV spectra. The environmental endpoint was completed as described in the RIFM Framework. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. 77 FR 22284 - Notice of Establishment of a Veterinary Services Stakeholder Registry

    Science.gov (United States)

    2012-04-13

    ... DEPARTMENT OF AGRICULTURE Animal and Plant Health Inspection Service [Docket No. APHIS-2012-0013] Notice of Establishment of a Veterinary Services Stakeholder Registry AGENCY: Animal and Plant Health... a Veterinary Services (VS) Stakeholder Registry, an email subscription service for individuals and...

  18. EPA Facility Registry Service (FRS): ER_FRP

    Data.gov (United States)

    U.S. Environmental Protection Agency — This dataset contains location and facility identification information from EPA's Facility Registry System (FRS) for the subset of facilities that link to Facility...

  19. Environmental Protection Agency (EPA) Facility Registry Service (FRS) Wastewater Treatment Plants

    Data.gov (United States)

    Department of Homeland Security — This GIS dataset contains data on wastewater treatment plants, based on EPA's Facility Registry Service (FRS) and NPDES, along with Clean Watersheds Needs Survey...

  20. Les TIC au service du microcrédit : le cas des correspondants ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Les TIC au service du microcrédit : le cas des correspondants bancaires au Brésil. Bien qu'il ait été prouvé que les programmes de microfinance constituaient un outil efficace pour lutter contre la pauvreté dans les pays en développement, ils tardent à prendre leur envol en Amérique latine, en particulier au Brésil.

  1. Utilization of chemical abstracts service (CAS) data bases

    International Nuclear Information System (INIS)

    Ehrhardt, F.; Gesellschaft Deutscher Chemiker, Berlin

    1979-04-01

    A method is developed describing the economic utilization of the Chemical Abstracts Service data bases CA Condensates and Chemical Abstracts Subject Index Alertin order to supplement the data base of the IDC-Inorganica-Documentationsystem built up to meet the peculiarities of the inorganic chemistry. The method consists of EDP-Programs and processes at which special authority files for coded compound and subject entries play an important role. One of the advantages of the method is that the intellectual effort necessary to create such a data base is reduced to a minimum. The authority files may be also used for orther purposes. (orig.) 891 WB 892 MB [de

  2. EPA Facility Registry Service (FRS): FRS_ESF3

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web service contains the following layers: WWTP -NPDES and WTP. The WWTP-NPDES facilties have associated CONTACTS, NAIP, SIC, and STATE IDs information. Layers...

  3. EPA Facility Registry Service (FRS): FRS_ESF10

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web service contains the following layers: RMP, TRI, FRP, RCRATSD, CERCLIS, TSCA, and E-PLAN facilities and their associated CONTACTS, CHEMICALS, NAIP, SIC, and...

  4. Evolution of Web Services in EOSDIS: Search and Order Metadata Registry (ECHO)

    Science.gov (United States)

    Mitchell, Andrew; Ramapriyan, Hampapuram; Lowe, Dawn

    2009-01-01

    During 2005 through 2008, NASA defined and implemented a major evolutionary change in it Earth Observing system Data and Information System (EOSDIS) to modernize its capabilities. This implementation was based on a vision for 2015 developed during 2005. The EOSDIS 2015 Vision emphasizes increased end-to-end data system efficiency and operability; increased data usability; improved support for end users; and decreased operations costs. One key feature of the Evolution plan was achieving higher operational maturity (ingest, reconciliation, search and order, performance, error handling) for the NASA s Earth Observing System Clearinghouse (ECHO). The ECHO system is an operational metadata registry through which the scientific community can easily discover and exchange NASA's Earth science data and services. ECHO contains metadata for 2,726 data collections comprising over 87 million individual data granules and 34 million browse images, consisting of NASA s EOSDIS Data Centers and the United States Geological Survey's Landsat Project holdings. ECHO is a middleware component based on a Service Oriented Architecture (SOA). The system is comprised of a set of infrastructure services that enable the fundamental SOA functions: publish, discover, and access Earth science resources. It also provides additional services such as user management, data access control, and order management. The ECHO system has a data registry and a services registry. The data registry enables organizations to publish EOS and other Earth-science related data holdings to a common metadata model. These holdings are described through metadata in terms of datasets (types of data) and granules (specific data items of those types). ECHO also supports browse images, which provide a visual representation of the data. The published metadata can be mapped to and from existing standards (e.g., FGDC, ISO 19115). With ECHO, users can find the metadata stored in the data registry and then access the data either

  5. Tools and data services registry: a community effort to document bioinformatics resources

    Science.gov (United States)

    Ison, Jon; Rapacki, Kristoffer; Ménager, Hervé; Kalaš, Matúš; Rydza, Emil; Chmura, Piotr; Anthon, Christian; Beard, Niall; Berka, Karel; Bolser, Dan; Booth, Tim; Bretaudeau, Anthony; Brezovsky, Jan; Casadio, Rita; Cesareni, Gianni; Coppens, Frederik; Cornell, Michael; Cuccuru, Gianmauro; Davidsen, Kristian; Vedova, Gianluca Della; Dogan, Tunca; Doppelt-Azeroual, Olivia; Emery, Laura; Gasteiger, Elisabeth; Gatter, Thomas; Goldberg, Tatyana; Grosjean, Marie; Grüning, Björn; Helmer-Citterich, Manuela; Ienasescu, Hans; Ioannidis, Vassilios; Jespersen, Martin Closter; Jimenez, Rafael; Juty, Nick; Juvan, Peter; Koch, Maximilian; Laibe, Camille; Li, Jing-Woei; Licata, Luana; Mareuil, Fabien; Mičetić, Ivan; Friborg, Rune Møllegaard; Moretti, Sebastien; Morris, Chris; Möller, Steffen; Nenadic, Aleksandra; Peterson, Hedi; Profiti, Giuseppe; Rice, Peter; Romano, Paolo; Roncaglia, Paola; Saidi, Rabie; Schafferhans, Andrea; Schwämmle, Veit; Smith, Callum; Sperotto, Maria Maddalena; Stockinger, Heinz; Vařeková, Radka Svobodová; Tosatto, Silvio C.E.; de la Torre, Victor; Uva, Paolo; Via, Allegra; Yachdav, Guy; Zambelli, Federico; Vriend, Gert; Rost, Burkhard; Parkinson, Helen; Løngreen, Peter; Brunak, Søren

    2016-01-01

    Life sciences are yielding huge data sets that underpin scientific discoveries fundamental to improvement in human health, agriculture and the environment. In support of these discoveries, a plethora of databases and tools are deployed, in technically complex and diverse implementations, across a spectrum of scientific disciplines. The corpus of documentation of these resources is fragmented across the Web, with much redundancy, and has lacked a common standard of information. The outcome is that scientists must often struggle to find, understand, compare and use the best resources for the task at hand. Here we present a community-driven curation effort, supported by ELIXIR—the European infrastructure for biological information—that aspires to a comprehensive and consistent registry of information about bioinformatics resources. The sustainable upkeep of this Tools and Data Services Registry is assured by a curation effort driven by and tailored to local needs, and shared amongst a network of engaged partners. As of November 2015, the registry includes 1785 resources, with depositions from 126 individual registrations including 52 institutional providers and 74 individuals. With community support, the registry can become a standard for dissemination of information about bioinformatics resources: we welcome everyone to join us in this common endeavour. The registry is freely available at https://bio.tools. PMID:26538599

  6. The design, construction and implementation of a computerised trauma registry in a developing South African metropolitan trauma service.

    Science.gov (United States)

    Laing, G L; Bruce, J L; Aldous, C; Clarke, D L

    2014-01-01

    The Pietermaritzburg Metropolitan Trauma Service formerly lacked a robust computerised trauma registry. This made surgical audit difficult for the purpose of quality of care improvement and development. We aimed to design, construct and implement a computerised trauma registry within our service. Twelve months following its implementation, we sought to examine and report on the quality of the registry. Formal ethical approval to maintain a computerised trauma registry was obtained prior to undertaking any design and development. Appropriate commercial software was sourced to develop this project. The registry was designed as a flat file. A flat file is a plain text or mixed text and binary file which usually contains one record per line or physical record. Thereafter the registry file was launched onto a secure server. This provided the benefits of access security and automated backups. Registry training was provided to clients by the developer. The exercise of data capture was then integrated into the process of service delivery, taking place at the endpoint of patient care (discharge, transfer or death). Twelve months following its implementation, the compliance rates of data entry were measured. The developer of this project managed to design, construct and implement an electronic trauma registry into the service. Twelve months following its implementation the data were extracted and audited to assess the quality. A total of 2640 patient entries were captured onto the registry. Compliance rates were in the order of eighty percent and client satisfaction rates were high. A number of deficits were identified. These included the omission of weekend discharges and underreporting of deaths. The construction and implementation of the computerised trauma registry was the beginning of an endeavour to continue improvements in the quality of care within our service. The registry provided a reliable audit at twelve months post implementation. Deficits and limitations were

  7. Using registries to integrate bioinformatics tools and services into workbench environments

    DEFF Research Database (Denmark)

    Ménager, Hervé; Kalaš, Matúš; Rapacki, Kristoffer

    2016-01-01

    The diversity and complexity of bioinformatics resources presents significant challenges to their localisation, deployment and use, creating a need for reliable systems that address these issues. Meanwhile, users demand increasingly usable and integrated ways to access and analyse data, especially......, a software component that will ease the integration of bioinformatics resources in a workbench environment, using their description provided by the existing ELIXIR Tools and Data Services Registry....

  8. 41 CFR 102-33.95 - What is the process for budgeting to acquire commercial aviation services (CAS)?

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false What is the process for budgeting to acquire commercial aviation services (CAS)? 102-33.95 Section 102-33.95 Public Contracts and... Parts The Process for Budgeting to Acquire Government Aircraft § 102-33.95 What is the process for...

  9. Towards a global service registry for the world-wide LHC computing grid

    International Nuclear Information System (INIS)

    Field, Laurence; Pradillo, Maria Alandes; Girolamo, Alessandro Di

    2014-01-01

    The World-Wide LHC Computing Grid encompasses a set of heterogeneous information systems; from central portals such as the Open Science Grid's Information Management System and the Grid Operations Centre Database, to the WLCG information system, where the information sources are the Grid services themselves. Providing a consistent view of the information, which involves synchronising all these informations systems, is a challenging activity that has lead the LHC virtual organisations to create their own configuration databases. This experience, whereby each virtual organisation's configuration database interfaces with multiple information systems, has resulted in the duplication of effort, especially relating to the use of manual checks for the handling of inconsistencies. The Global Service Registry aims to address this issue by providing a centralised service that aggregates information from multiple information systems. It shows both information on registered resources (i.e. what should be there) and available resources (i.e. what is there). The main purpose is to simplify the synchronisation of the virtual organisation's own configuration databases, which are used for job submission and data management, through the provision of a single interface for obtaining all the information. By centralising the information, automated consistency and validation checks can be performed to improve the overall quality of information provided. Although internally the GLUE 2.0 information model is used for the purpose of integration, the Global Service Registry in not dependent on any particular information model for ingestion or dissemination. The intention is to allow the virtual organisation's configuration databases to be decoupled from the underlying information systems in a transparent way and hence simplify any possible future migration due to the evolution of those systems. This paper presents the Global Service Registry architecture, its advantages

  10. Towards a Global Service Registry for the World-Wide LHC Computing Grid

    Science.gov (United States)

    Field, Laurence; Alandes Pradillo, Maria; Di Girolamo, Alessandro

    2014-06-01

    The World-Wide LHC Computing Grid encompasses a set of heterogeneous information systems; from central portals such as the Open Science Grid's Information Management System and the Grid Operations Centre Database, to the WLCG information system, where the information sources are the Grid services themselves. Providing a consistent view of the information, which involves synchronising all these informations systems, is a challenging activity that has lead the LHC virtual organisations to create their own configuration databases. This experience, whereby each virtual organisation's configuration database interfaces with multiple information systems, has resulted in the duplication of effort, especially relating to the use of manual checks for the handling of inconsistencies. The Global Service Registry aims to address this issue by providing a centralised service that aggregates information from multiple information systems. It shows both information on registered resources (i.e. what should be there) and available resources (i.e. what is there). The main purpose is to simplify the synchronisation of the virtual organisation's own configuration databases, which are used for job submission and data management, through the provision of a single interface for obtaining all the information. By centralising the information, automated consistency and validation checks can be performed to improve the overall quality of information provided. Although internally the GLUE 2.0 information model is used for the purpose of integration, the Global Service Registry in not dependent on any particular information model for ingestion or dissemination. The intention is to allow the virtual organisation's configuration databases to be decoupled from the underlying information systems in a transparent way and hence simplify any possible future migration due to the evolution of those systems. This paper presents the Global Service Registry architecture, its advantages compared to the

  11. EMI Registry Design

    CERN Document Server

    Memon, S

    2011-01-01

    Grid services are the fundamental building blocks of today's Distributed Computing Infrastructures (DCI). The discovery of services in the DCI is a primary function that is a precursor to other tasks such as workload and data management. In this context, a service registry can be used to fulfil such a requirement. Existing service registries, such as the ARC Information Index or UNICORE Registry, are examples that have proven themselves in production environments. Such implementations provide a centralized service registry, however, todays DCIs, such as EGI, are based on a federation model. It is therefore necessary for the service registry to mirror such a model in order for it to seamlessly fit into the operational and management requirements - a DCI built using federated approach. This document presents an architecture for a federated service registry and a prototype based on this architecture, the EMI Registry. Special attention is given to how the federated service registry is robust to environment failu...

  12. 78 FR 1825 - Notice of Establishment of an Animal and Plant Health Inspection Service Stakeholder Registry

    Science.gov (United States)

    2013-01-09

    ... CONTACT: Ms. Hallie Zimmers, Advisor for State and Stakeholder Relations, Legislative and Public Affairs... communication with our many and diverse stakeholders. To join the registry and receive messages, stakeholders... subscriptions may access the expanded registry at: https://public.govdelivery.com/accounts/USDAAPHIS/subscriber...

  13. RIFM fragrance ingredient safety assessment, acetic acid, C7-9-branched alkyl esters, C8-rich, CAS Registry Number 108419-32-5.

    Science.gov (United States)

    Api, A M; Belsito, D; Botelho, D; Browne, D; Bruze, M; Burton, G A; Buschmann, J; Calow, P; Dagli, M L; Date, M; Dekant, W; Deodhar, C; Fryer, A D; Joshi, K; La Cava, S; Lapczynski, A; Liebler, D C; O'Brien, D; Parakhia, R; Patel, A; Penning, T M; Ritacco, G; Romine, J; Salvito, D; Schultz, T W; Sipes, I G; Thakkar, Y; Tsang, S; Wahler, J

    2017-12-01

    The use of this material under current conditions is supported by existing information. This material was evaluated for genotoxicity, repeated dose toxicity, developmental and reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, as well as environmental safety. Data show that this material is not genotoxic. Data from the suitable read across analog isoamyl acetate (CAS# 123-92-2) show that this material does not have skin sensitization potential. The reproductive and local respiratory toxicity endpoints were completed using the TTC (Threshold of Toxicological Concern) for a Cramer Class I material (0.03 mg/kg/day and 1.4 mg/day, respectively). The repeated dose and developmental endpoint was completed using data on the target material, which provided a MOE > 100. The phototoxicity/photoallergenicity endpoint was completed based on suitable UV spectra. The environmental endpoint was completed as described in the RIFM Framework. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Perspectives d'introduction d'un marketing des services au sein des banques publiques Algériennes : Cas de la B.A.D.R.

    OpenAIRE

    Lachachi-taleb, Meriem

    2014-01-01

    Le premier chapitre présente les fondements théoriques relatifs au marketing des services ainsi qu'au concept de servuction et enfin au marketing mix des services dans le deuxiéme chapitre.Le troisiéme chapitre est consacré au marketing bancaire et au plan marketing dans le chapitre suivant, une étude de cas au sein de la B.A.D.R.Banque.

  15. Contextualized B2B Registries

    OpenAIRE

    Radetzki, U; Boniface, M.J.; Surridge, M.

    2007-01-01

    Abstract. Service discovery is a fundamental concept underpinning the move towards dynamic service-oriented business partnerships. The business process for integrating service discovery and underlying registry technologies into busi-ness relationships, procurement and project management functions has not been examined and hence existing Web Service registries lack capabilities required by business today. In this paper we present a novel contextualized B2B registry that supports dynamic regist...

  16. The GEOSS User Requirement Registry (URR): A Cross-Cutting Service-Oriented Infrastructure Linking Science, Society and GEOSS

    Science.gov (United States)

    Plag, H.-P.; Foley, G.; Jules-Plag, S.; Ondich, G.; Kaufman, J.

    2012-04-01

    The Group on Earth Observations (GEO) is implementing the Global Earth Observation System of Systems (GEOSS) as a user-driven service infrastructure responding to the needs of users in nine interdependent Societal Benefit Areas (SBAs) of Earth observations (EOs). GEOSS applies an interdisciplinary scientific approach integrating observations, research, and knowledge in these SBAs in order to enable scientific interpretation of the collected observations and the extraction of actionable information. Using EOs to actually produce these societal benefits means getting the data and information to users, i.e., decision-makers. Thus, GEO needs to know what the users need and how they would use the information. The GEOSS User Requirements Registry (URR) is developed as a service-oriented infrastructure enabling a wide range of users, including science and technology (S&T) users, to express their needs in terms of EOs and to understand the benefits of GEOSS for their fields. S&T communities need to be involved in both the development and the use of GEOSS, and the development of the URR accounts for the special needs of these communities. The GEOSS Common Infrastructure (GCI) at the core of GEOSS includes system-oriented registries enabling users to discover, access, and use EOs and derived products and services available through GEOSS. In addition, the user-oriented URR is a place for the collection, sharing, and analysis of user needs and EO requirements, and it provides means for an efficient dialog between users and providers. The URR is a community-based infrastructure for the publishing, viewing, and analyzing of user-need related information. The data model of the URR has a core of seven relations for User Types, Applications, Requirements, Research Needs, Infrastructure Needs, Technology Needs, and Capacity Building Needs. The URR also includes a Lexicon, a number of controlled vocabularies, and

  17. Cas Wepener

    African Journals Online (AJOL)

    Owner

    Dubbelfoto is die eerste kortverhaalbundel van die teoloog Cas Wepener wat tot dusver veral akademiese artikels en godsdienstige boeke geskryf het. Die bundel se titel gee besondere prominensie aan die gegewe van die foto ter- wyl die motto wat gehaal is uit Roland Barthes se Camera Lucida die aandag vestig op die ...

  18. Achieving Interoperability Through Base Registries for Governmental Services and Document Management

    Science.gov (United States)

    Charalabidis, Yannis; Lampathaki, Fenareti; Askounis, Dimitris

    As digital infrastructures increase their presence worldwide, following the efforts of governments to provide citizens and businesses with high-quality one-stop services, there is a growing need for the systematic management of those newly defined and constantly transforming processes and electronic documents. E-government Interoperability Frameworks usually cater to the technical standards of e-government systems interconnection, but do not address service composition and use by citizens, businesses, or other administrations.

  19. Publishing and Discovering Business Services on Private Business Registry in B2B Environment

    Directory of Open Access Journals (Sweden)

    Nizamuddin Channa

    2013-07-01

    Full Text Available The need of data and information is crucial to the human users. WWW (World Wide Web plays a major role for fulfilling their needs, but sometimes all the purposes of human users are not achieved from the limited structure of the data available on the internet. However, the requirements of the accessibility of the data by users have also been changed and the same data is required in machine understandable form. IT (Information Technology has become mandatory to convert the existing web from people-centric to software application-centric. The WS (Web Services provide the suitable solution for application-to-application interoperability and integration over the Internet. WS is a promising technology that make available extensible and logical infrastructure for application to application communication constructed based on the current Web standards. The most accepted charm of the WS architecture is SOA (Service Oriented Architecture. The major roles involved in the WS infrastructure are service broker, service consumer/client and service provider. The technical pillars of WSs involve SOAP (Simple Object Access Protocol, WSDL (Web Service Description Language and UDDI (Universal Description and Directory Service. By looking at the core pillars of the SOA triangle, we have investigated and explored all implementation aspects of the WSDL, SOAP and UDDI. We have further explored what UDDI is, structure of UDDI. How to create and publish WSDL into UDDI via SOAP, Operations of UDDI, how to access UDDI using java and SOAP clients. The extensive exploration of the work on UDDI implementation, help the researchers benefiting from our implementations into their core web service researches such as composition, discovery, choreography, orchestration Semantic WS.

  20. Effect of weather and time on trauma events determined using emergency medical service registry data.

    Science.gov (United States)

    Lin, Li-Wei; Lin, Hsiao-Yu; Hsu, Chien-Yeh; Rau, Hsiao-Hsien; Chen, Ping-Ling

    2015-09-01

    Trauma admissions are associated with weather and temporal factors; however, previous study results regarding these factors are contradictory. We hypothesised that weather and temporal factors have different effects on specific trauma events in an emergency medical service (EMS) system. EMS data from January 1, 2009, to December 31, 2010, were obtained from the fire department of Taipei City and associated with the local weather data. EMS trauma events were categorised into total trauma, traffic accidents (TAs), motorbike accidents (MBAs), and falls. Hourly data on trauma patients were analysed using the zero-inflated Poisson model. The hourly incidence of total trauma increased with the magnitude of precipitation (incidence rate ratio [IRR]=1.06, 1.09, and 1.11 in light, moderate, and heavy rain, respectively), and this effect was more prominent in fall patients than in patients with other injuries (IRR=1.07, 1.21, and 1.32). However, the hourly incidence of TAs and MBAs was associated only with light rain (IRR=1.11 and 1.06, respectively). An hour of sunshine exposure was associated with an increase in the hourly incidence of all groups, and higher temperatures were associated with an increased hourly incidence of total trauma, TAs, and MBAs, but not falls. The hourly incidence of falls increased only in late fall and winter. Compared with the hourly incidence between 3 am and 7 am, the hourly incidence of all groups plateaued between 7 am and 11 pm and declined from 11 pm to 3 am. During the plateau period, 2 peaks in the incidence of TAs (IRR=5.03 and 5.07, respectively) and MBAs (IRR=5.81 and 5.51, respectively) were observed during 7-11 am and 3-7 pm. The hourly incidence of total trauma, TAs, and MBAs plateaued during workdays, peaked on Fridays, declined on Saturdays, and troughed on Sundays. The incidence of falls increased only on Mondays (IRR=1.09). Weather and temporal factors had different impacts on the incidence of traffic-related accidents and falls

  1. United States transuranium and uranium registries - 25 years of growth, research, and service. Annual report, April 1992--September 1993

    International Nuclear Information System (INIS)

    Kathren, R.L.; Harwick, L.A.; Toohey, R.E.; Russell, J.J.; Filipy, R.E.; Dietert, S.E.; Hunacek, M.M.; Hall, C.A.

    1994-01-01

    The Registries originated in 1968 as the National Plutonium Registry with the name changed to the United States Transuranium Registry the following year to reflect a broader concern with the heavier actinides as well. Initially, the scientific effort of the USTR was directed towards study of the distribution and dose of plutonium and americium in occupationally exposed persons, and to assessment of the effects of exposure to the transuranium elements on health. This latter role was reassessed during the 1970's when it was recognized that the biased cohort of the USTR was inappropriate for epidemiologic analysis. In 1978, the administratively separate but parallel United States Uranium Registry was created to carry out similar work among persons exposed to uranium and its decay products. A seven member scientific advisory committee provided guidance and scientific oversight. In 1992, the two Registries were administratively combined and transferred from the purview of a Department of Energy contractor to Washington State University under the provisions of a grant. Scientific results for the first twenty-five years of the Registries are summarized, including the 1985 publication of the analysis of the first whole body donor. Current scientific work in progress is summarized along with administrative activities for the period

  2. United States transuranium and uranium registries - 25 years of growth, research, and service. Annual report, April 1992--September 1993

    Energy Technology Data Exchange (ETDEWEB)

    Kathren, R.L.; Harwick, L.A.; Toohey, R.E.; Russell, J.J.; Filipy, R.E.; Dietert, S.E.; Hunacek, M.M.; Hall, C.A.

    1994-10-01

    The Registries originated in 1968 as the National Plutonium Registry with the name changed to the United States Transuranium Registry the following year to reflect a broader concern with the heavier actinides as well. Initially, the scientific effort of the USTR was directed towards study of the distribution and dose of plutonium and americium in occupationally exposed persons, and to assessment of the effects of exposure to the transuranium elements on health. This latter role was reassessed during the 1970`s when it was recognized that the biased cohort of the USTR was inappropriate for epidemiologic analysis. In 1978, the administratively separate but parallel United States Uranium Registry was created to carry out similar work among persons exposed to uranium and its decay products. A seven member scientific advisory committee provided guidance and scientific oversight. In 1992, the two Registries were administratively combined and transferred from the purview of a Department of Energy contractor to Washington State University under the provisions of a grant. Scientific results for the first twenty-five years of the Registries are summarized, including the 1985 publication of the analysis of the first whole body donor. Current scientific work in progress is summarized along with administrative activities for the period.

  3. The CAS Classroom

    Science.gov (United States)

    Garner, Sue

    2004-01-01

    The Victorian Curriculum and Assessment Authority (VCAA) Computer Algebra System (CAS)Pilot study (2001-2005) is monitoring the use of CAS in senior secondary mathematics. This article explores the author's experiences in the CAS classroom and delineates changes in teaching style, as a result of the introduction of CAS into the senior mathematics…

  4. Situation a-didactique et dispositif d’apprentissage instrumenté : cas de construction de projets de service

    Directory of Open Access Journals (Sweden)

    Bernard Coulibaly

    2011-01-01

    Full Text Available Dans cette contribution nous tentons d’analyser une situation didactique instrumentée sur une plate forme d’apprentissage à distance, situation dans laquelle des étudiants de Master 2 professionnel sont invités à réaliser un projet de service fictif. Cet apprentissage s’opère en groupe de 3 à 4 étudiants et vise l’acquisition de compétences en matière de conduite de projet de service dans le domaine de l’ingénierie en milieu socio-éducatif. L’article analyse, à partir des traces d’interaction, le processus de construction de ces savoir-faire en management de projet. Il met en évidence les stratégies de contournement et d’adaptation que les ��tudiants élaborent pour échapper aux contraintes d’une situation didactique fondée sur un dispositif pédagogique instrumenté .Il permet ainsi de comprendre le rôle que des apprenants peuvent jouer dans la conception d’une situation didactique.In this paper we analyze an instrumented didactic situation that takes place on a distance learning platform. In this situation students in a professional master’s degree curriculum are invited to create a fictitious service project. They have to achieve this task in groups of 3 to 4 students. The task aims at making students acquire competences in terms of project management in the field of educational engineering. The article analyzes the process of building these skills in project management from traces of interaction. It highlights the strategies of circumvention and adaptation that students develop to escape the constraints of a teaching situation based on an instrumented educational device. It helps understand the role that learners can play in the design of a teaching situation.

  5. Clinical Case Registries (CCR)

    Data.gov (United States)

    Department of Veterans Affairs — The Clinical Case Registries (CCR) replaced the former Immunology Case Registry and the Hepatitis C Case Registry with local and national databases. The CCR:HIV and...

  6. Converged Registries Solution (CRS)

    Data.gov (United States)

    Department of Veterans Affairs — The Converged Registries platform is a hardware and software architecture designed to host individual patient registries and eliminate duplicative development effort...

  7. Surgeon length of service and risk-adjusted outcomes: linked observational analysis of the UK National Adult Cardiac Surgery Audit Registry and General Medical Council Register.

    Science.gov (United States)

    Hickey, Graeme L; Grant, Stuart W; Freemantle, Nick; Cunningham, David; Munsch, Christopher M; Livesey, Steven A; Roxburgh, James; Buchan, Iain; Bridgewater, Ben

    2014-09-01

    To explore the relationship between in-hospital mortality following adult cardiac surgery and the time since primary clinical qualification for the responsible consultant cardiac surgeon (a proxy for experience). Retrospective analysis of prospectively collected national registry data over a 10-year period using mixed-effects multiple logistic regression modelling. Surgeon experience was defined as the time between the date of surgery and award of primary clinical qualification. UK National Health Service hospitals performing cardiac surgery between January 2003 and December 2012. All patients undergoing coronary artery bypass grafts and/or valve surgery under the care of a consultant cardiac surgeon. All-cause in-hospital mortality. A total of 292,973 operations performed by 273 consultant surgeons (with lengths of service from 11.2 to 42.0 years) were included. Crude mortality increased approximately linearly until 33 years service, before decreasing. After adjusting for case-mix and year of surgery, there remained a statistically significant (p=0.002) association between length of service and in-hospital mortality (odds ratio 1.013; 95% CI 1.005-1.021 for each year of 'experience'). Consultant cardiac surgeons take on increasingly complex surgery as they gain experience. With this progression, the incidence of adverse outcomes is expected to increase, as is demonstrated in this study. After adjusting for case-mix using the EuroSCORE, we observed an increased risk of mortality in patients operated on by longer serving surgeons. This finding may reflect under-adjustment for risk, unmeasured confounding or a real association. Further research into outcomes over the time course of surgeon's careers is required. © The Royal Society of Medicine.

  8. Nanomaterial Registry

    Data.gov (United States)

    U.S. Department of Health & Human Services — By leveraging and developing a set of Minimal Information About Nanomaterials (MIAN), ontology and standards through a community effort, it has developed a data...

  9. Ponction biopsies rénales dans le Service de Néphrologie de Fès: indications et résultats: à propos de 522 cas

    Science.gov (United States)

    Mbarki, Houda; Belghiti, Khadija Alaoui; Harmouch, Taoufiq; Najdi, Adil; Arrayhani, Mohamed; Sqalli, Tarik

    2016-01-01

    L'apport de la ponction biopsie rénale (PBR) dans le diagnostic, le choix thérapeutique et l’évaluation pronostique des néphropathies est considérable. Aucune étude marocaine n'a évalué la pratique et l'apport de la PBR. Notre objectif est d’étudier les indications de la PBR, déterminer la fréquence des maladies rénales identifiées par PBR dans notre région et de faire une confrontation entre les données clinico-biologiques et le diagnostic historique. Notre étude menée entre Janvier 2009 et Décembre 2012, est rétrospective. Nous avons inclus tous les patients du service de Néphrologie du CHU Hassan II de Fès ayant bénéficié d'une biopsie de reins natifs. 522 PBR ont été réalisées. Nous avons exclu 8 biopsies devant le manque de renseignements et avons donc retenu 514. L’âge moyen des patients au moment de la PBR est de 39 ±17 ans (3-82 ans). Le sex ratio est de 0,9. Le syndrome néphrotique est le diagnostic clinique le plus fréquent à tous les âges (58,2%). Les néphropathies glomérulaires représentent 94,2% des maladies rénales diagnostiquées, leur distribution varie selon l’âge des patients. La PBR a confirmé le premier diagnostic suspecté cliniquement dans 40,65% des cas, alors qu'elle a révélé un diagnostic inattendu chez 22,5% d'entre eux. Le diagnostic syndromique permet d'orienter vers la maladie rénale la plus probable et de guider les thérapeutiques urgentes en attendant les résultats de la PBR. Mais il ne peut en aucun remplacer la PBR qui reste le gold standard. PMID:27583085

  10. On Domain Registries and Website Content

    DEFF Research Database (Denmark)

    Schwemer, Sebastian Felix

    2018-01-01

    such as Internet access service providers, hosting platforms, and websites that link to content. This article shows that in recent years, however, that the (secondary) liability of domain registries and registrars, and more specifically country code top-level domain registries (ccTLDs) for website content, has...... been tested in several EU Member States. The article investigates tendencies in the national lower-court jurisprudence and explores to what extent the liability exemption regime of the E-Commerce Directive applies to domain registries. The analysis concludes that whereas domain registries fall under...

  11. Applying Registry Services to Spaceflight Technologies to Aid in the Assignment of Assigned Numbers to Disparate Systems and their Technologies to Further Enable Interoperability

    Science.gov (United States)

    Bradford, Robert N.; Nichols, Kelvin F.; Witherspoon, Keith R.

    2006-01-01

    To date very little effort has been made to provide interoperability between various space agency projects. To effectively get to the Moon and beyond systems must interoperate. To provide interoperability, standardization and registries of various technologies will be required. These registries will be created as they relate to space flight. With the new NASA Moon/Mars initiative, a requirement to standardize and control the naming conventions of very disparate systems and technologies is emerging. The need to provide numbering to the many processes, schemas, vehicles, robots, space suits and technologies (e.g. versions), to name a few, in the highly complex Constellation initiative is imperative. The number of corporations, developer personnel, system interfaces, people interfaces will require standardization and registries on a scale not currently envisioned. It would only take one exception (stove piped system development) to weaken, if not, destroy interoperability. To start, a standardized registry process must be defined that allows many differing engineers, organizations and operators the ability to easily access disparate registry information across numerous technological and scientific disciplines. Once registries are standardized the need to provide registry support in terms of setup and operations, resolution of conflicts between registries and other issues will need to be addressed. Registries should not be confused with repositories. No end user data is "stored" in a registry nor is it a configuration control system. Once a registry standard is created and approved, the technologies that should be registered must be identified and prioritized. In this paper, we will identify and define a registry process that is compatible with the Constellation initiative and other non related space activities and organizations. We will then identify and define the various technologies that should use a registry to provide interoperability. The first set of

  12. Analysis of occupational doses of workers on the dose registry of the Federal Radiation Protection Service in 2000 and 2001

    International Nuclear Information System (INIS)

    Ogundare, F.O.; Balogun, F.A.

    2003-01-01

    In 2000 and 2001 about 279 and 221 radiation workers, respectively, were monitored by the Federal Radiation Protection Service, University of Ibadan, in Nigeria. The distribution of the occupational doses shows that the majority of workers received doses below 4 mSv in each of the two years. The radiation workers in the two years are classified into two occupational categories: medicine and industry. The mean annual effective doses, collective doses and the collective dose distribution ratios for workers in each category and the entire monitored workers were calculated. The mean annual effective doses were compared with their corresponding worldwide values quoted by UNSCEAR. In each of the two years, a few workers in industry received doses higher than 50 mSv. The collective dose distribution ratio was found to be about 0.49, which is very close to the highest value of 0.5 in the range of values considered by UNSCEAR as normal for this parameter. This suggests that extra measures have to be taken, particularly in industry, to ensure that the proportion of workers at risk does not go outside this normal range. The occupational doses were also modelled by both the log-normal and Weibull distributions. Both distributions were found to describe the data in almost the same way. (author)

  13. Substance Identification Information from EPA's Substance Registry

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Substance Registry Services (SRS) is the authoritative resource for basic information about substances of interest to the U.S. EPA and its state and tribal...

  14. Linking Medicare, Medicaid, and Cancer Registry Data...

    Data.gov (United States)

    U.S. Department of Health & Human Services — Linking Medicare, Medicaid, and Cancer Registry Data to Study the Burden of Cancers in West Virginia In the United States, the elderly carry an unequal burden of...

  15. EPA Facility Registry System (FRS): NCES

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web feature service contains location and facility identification information from EPA's Facility Registry System (FRS) for the subset of facilities that link...

  16. EPA Facility Registry System (FRS): NEPT

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web feature service contains location and facility identification information from EPA's Facility Registry System (FRS) for the subset of facilities that link...

  17. Asteroid named after CAS scientist

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ An asteroid has been named after CAS astronomy historian XI Zezong with the approval of the International Minor Planet Nomenclature Committee (IMPNC), announced China's National Astronomical Observatories at CAS (NAOC) on 17 August.

  18. Second generation registry framework.

    Science.gov (United States)

    Bellgard, Matthew I; Render, Lee; Radochonski, Maciej; Hunter, Adam

    2014-01-01

    Information management systems are essential to capture data be it for public health and human disease, sustainable agriculture, or plant and animal biosecurity. In public health, the term patient registry is often used to describe information management systems that are used to record and track phenotypic data of patients. Appropriate design, implementation and deployment of patient registries enables rapid decision making and ongoing data mining ultimately leading to improved patient outcomes. A major bottleneck encountered is the static nature of these registries. That is, software developers are required to work with stakeholders to determine requirements, design the system, implement the required data fields and functionality for each patient registry. Additionally, software developer time is required for ongoing maintenance and customisation. It is desirable to deploy a sophisticated registry framework that can allow scientists and registry curators possessing standard computing skills to dynamically construct a complete patient registry from scratch and customise it for their specific needs with little or no need to engage a software developer at any stage. This paper introduces our second generation open source registry framework which builds on our previous rare disease registry framework (RDRF). This second generation RDRF is a new approach as it empowers registry administrators to construct one or more patient registries without software developer effort. New data elements for a diverse range of phenotypic and genotypic measurements can be defined at any time. Defined data elements can then be utilised in any of the created registries. Fine grained, multi-level user and workgroup access can be applied to each data element to ensure appropriate access and data privacy. We introduce the concept of derived data elements to assist the data element standards communities on how they might be best categorised. We introduce the second generation RDRF that

  19. Tools and data services registry

    DEFF Research Database (Denmark)

    Ison, Jon; Rapacki, Kristoffer; Ménager, Hervé

    2016-01-01

    Life sciences are yielding huge data sets that underpin scientific discoveries fundamental to improvement in human health, agriculture and the environment. In support of these discoveries, a plethora of databases and tools are deployed, in technically complex and diverse implementations, across...... a spectrum of scientific disciplines. The corpus of documentation of these resources is fragmented across the Web, with much redundancy, and has lacked a common standard of information. The outcome is that scientists must often struggle to find, understand, compare and use the best resources for the task...

  20. Tools and data services registry

    DEFF Research Database (Denmark)

    Ison, Jon; Rapacki, Kristoffer; Ménager, Hervé

    2016-01-01

    Life sciences are yielding huge data sets that underpin scientific discoveries fundamental to improvement in human health, agriculture and the environment. In support of these discoveries, a plethora of databases and tools are deployed, in technically complex and diverse implementations, across a...

  1. CRISPR-Cas

    NARCIS (Netherlands)

    Jackson, Simon A.; McKenzie, Rebecca E.; Fagerlund, Robert D.; Kieper, Sebastian N.; Fineran, Peter C.; Brouns, Stan J.J.

    2017-01-01

    Bacteria and archaea are engaged in a constant arms race to defend against the ever-present threats of viruses and invasion by mobile genetic elements. The most flexible weapons in the prokaryotic defense arsenal are the CRISPR-Cas adaptive immune systems. These systems are capable of selective

  2. Linkage between the Danish National Health Service Prescription Database, the Danish Fetal Medicine Database, and other Danish registries as a tool for the study of drug safety in pregnancy

    Directory of Open Access Journals (Sweden)

    Pedersen LH

    2016-05-01

    Full Text Available Lars H Pedersen,1,2 Olav B Petersen,1,2 Mette Nørgaard,3 Charlotte Ekelund,4 Lars Pedersen,3 Ann Tabor,4 Henrik T Sørensen3 1Department of Clinical Medicine, Aarhus University, 2Department of Obstetrics and Gynecology, 3Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, 4Department of Fetal Medicine, Rigshospitalet, Copenhagen, Denmark Abstract: A linked population-based database is being created in Denmark for research on drug safety during pregnancy. It combines information from the Danish National Health Service Prescription Database (with information on all prescriptions reimbursed in Denmark since 2004, the Danish Fetal Medicine Database, the Danish National Registry of Patients, and the Medical Birth Registry. The new linked database will provide validated information on malformations diagnosed both prenatally and postnatally. The cohort from 2008 to 2014 will comprise 589,000 pregnancies with information on 424,000 pregnancies resulting in live-born children, ~420,000 pregnancies undergoing prenatal ultrasound scans, 65,000 miscarriages, and 92,000 terminations. It will be updated yearly with information on ~80,000 pregnancies. The cohort will enable identification of drug exposures associated with severe malformations, not only based on malformations diagnosed after birth but also including those having led to termination of pregnancy or miscarriage. Such combined data will provide a unique source of information for research on the safety of medications used during pregnancy. Keywords: malformations, teratology, therapeutic drug monitoring, epidemiological methods, registries

  3. Use of general practice, diagnostic investigations and hospital services before and after cancer diagnosis - a population-based nationwide registry study of 127,000 incident adult cancer patients

    Directory of Open Access Journals (Sweden)

    Christensen Karina

    2012-07-01

    Full Text Available Abstract Background Knowledge of patterns in cancer patients’ health care utilisation around the time of diagnosis may guide health care resource allocation and provide important insights into this groups’ demand for health care services. The health care need of patients with comorbid conditions far exceeds the oncology capacity and it is therefore important to elucidate the role of both primary and secondary care. The aim of this paper is to describe the use of health care services amongst incident cancer patients in Denmark one year before and one year after cancer diagnosis. Methods The present study is a national population-based case–control (1:10 registry study. All incident cancer patients (n = 127,210 diagnosed between 2001 and 2006 aged 40 years or older were identified in the Danish Cancer Registry. Data from national health registries were provided for all cancer patients and for 1,272,100 controls. Monthly consultation frequencies, monthly proportions of persons receiving health services and three-month incidence rate ratios for one year before and one year after the cancer diagnosis were calculated. Data were analysed separately for women and men. Results Three months before their diagnosis, cancer patients had twice as many general practitioner (GP consultations, ten to eleven times more diagnostic investigations and five times more hospital contacts than the reference population. The demand for GP services peaked one month before diagnosis, the demand for diagnostic investigations one month after diagnosis and the number of hospital contacts three months after diagnosis. The proportion of cancer patients receiving each of these three types of health services remained more than 10% above that of the reference population from two months before diagnosis until the end of the study period. Conclusions Cancer patients’ health service utilisation rose dramatically three months before their diagnosis. This increase applied to

  4. How type II CRISPR-Cas establish immunity through Cas1-Cas2-mediated spacer integration.

    Science.gov (United States)

    Xiao, Yibei; Ng, Sherwin; Nam, Ki Hyun; Ke, Ailong

    2017-10-05

    CRISPR (clustered regularly interspaced short palindromic repeats) and the nearby Cas (CRISPR-associated) operon establish an RNA-based adaptive immunity system in prokaryotes. Molecular memory is created when a short foreign DNA-derived prespacer is integrated into the CRISPR array as a new spacer. Whereas the RNA-guided CRISPR interference mechanism varies widely among CRISPR-Cas systems, the spacer integration mechanism is essentially identical. The conserved Cas1 and Cas2 proteins form an integrase complex consisting of two distal Cas1 dimers bridged by a Cas2 dimer. The prespacer is bound by Cas1-Cas2 as a dual-forked DNA, and the terminal 3'-OH of each 3' overhang serves as an attacking nucleophile during integration. The prespacer is preferentially integrated into the leader-proximal region of the CRISPR array, guided by the leader sequence and a pair of inverted repeats inside the CRISPR repeat. Spacer integration in the well-studied Escherichia coli type I-E CRISPR system also relies on the bacterial integration host factor. In type II-A CRISPR, however, Cas1-Cas2 alone integrates spacers efficiently in vitro; other Cas proteins (such as Cas9 and Csn2) have accessory roles in the biogenesis phase of prespacers. Here we present four structural snapshots from the type II-A system of Enterococcus faecalis Cas1 and Cas2 during spacer integration. Enterococcus faecalis Cas1-Cas2 selectively binds to a splayed 30-base-pair prespacer bearing 4-nucleotide 3' overhangs. Three molecular events take place upon encountering a target: first, the Cas1-Cas2-prespacer complex searches for half-sites stochastically, then it preferentially interacts with the leader-side CRISPR repeat, and finally, it catalyses a nucleophilic attack that connects one strand of the leader-proximal repeat to the prespacer 3' overhang. Recognition of the spacer half-site requires DNA bending and leads to full integration. We derive a mechanistic framework to explain the stepwise spacer

  5. EMI Registry Development Plan

    CERN Document Server

    Memon, S.; Szigeti, G.; Field, L.

    2012-01-01

    This documents describes the overall development plan of the EMI Registry product, the plan focuses on the realisation of the EMI Registry specification as defined in the document. It is understood that during the course of the development phase the specification will likely evolve and the changes will be fed into the specification document.

  6. The Qingdao Twin Registry

    DEFF Research Database (Denmark)

    Duan, Haiping; Ning, Feng; Zhang, Dongfeng

    2013-01-01

    In 1998, the Qingdao Twin Registry was initiated as the main part of the Chinese National Twin Registry. By 2005, a total of 10,655 twin pairs had been recruited. Since then new twin cohorts have been sampled, with one longitudinal cohort of adolescent twins selected to explore determinants of me...

  7. Assessing Ontario's Personal Support Worker Registry

    Directory of Open Access Journals (Sweden)

    Audrey Laporte

    2013-08-01

    Full Text Available In response to the growing role of personal support workers (PSWs in the delivery of health care services to Ontarians, the Ontario government has moved forward with the creation of a PSW registry. This registry will be mandatory for all PSWs employed by publicly funded health care employers, and has the stated objectives of better highlighting the work that PSWs do in Ontario, providing a platform for PSWs and employers to more easily access the labour market, and to provide government with information for human resources planning. In this paper we consider the factors that brought the creation of a PSW registry onto the Ontario government’s policy agenda, discuss how the registry is being implemented, and provide an analysis of the strengths and weaknesses of this policy change.

  8. 76 FR 36896 - Notice of Establishment of a New Plant Protection and Quarantine Stakeholder Registry

    Science.gov (United States)

    2011-06-23

    ... Quarantine Stakeholder Registry AGENCY: Animal and Plant Health Inspection Service, USDA. ACTION: Notice.... FOR FURTHER INFORMATION CONTACT: For information on the PPQ Stakeholder Registry, contact Ms. Donna L... Quarantine (PPQ) stakeholder registry is an email subscription service that allows individuals to receive...

  9. Payments for Environmental Services: Can They Work? Systèmes de paiement pour services environnementaux : une solution efficace ? Le cas du Mexique Pago por Servicios Ambientales: ¿Pueden funcionar? El caso de México

    Directory of Open Access Journals (Sweden)

    Helena García Romero

    2012-06-01

    Full Text Available Payments for Environmental Services (PES Programs can be useful policy instruments for achieving conservation objectives through incentive mechanisms.  However, the success of such programs depends on the particular solutions that are given to political economy constraints and challenges. The Mexican case provides helpful lessons on this topic, in addition to design and implementation insights.The Mexican PES program has been in place since 2003.  It strives to protect well-conserved forests and to have a social impact through payments made to the most marginalized communities.  Nevertheless, its impact in terms of avoided deforestation is not very high. This is due to targeting failures that arise from an internal trade-off between social and conservation goals.  In order to align both objectives the continuous negotiation of goals and targeting mechanisms between the different stakeholders: government, bureaucracy, non-government organizations (NGOs, and local communities must be kept in mind. Understanding and anticipating this policy process can ensure the desirable outcomes of PES programs in terms of poverty alleviation and conservation.Les programmes de systèmes de paiement pour services environnementaux (PES - Payments for Environmental Services peuvent être des instruments d’intervention efficaces pour atteindre les objectifs en matière de conservation des écosystèmes grâce aux mesures d’incitation qu’ils englobent. La réussite de ce type de programmes dépend toutefois des solutions spécifiques mises en place pour répondre aux contraintes et problématiques de l’économie politique. Le cas du Mexique permet de tirer des enseignements utiles à ce sujet et donne des éclairages sur la manière de concevoir et de mettre en oeuvre ces programmes.Le programme PES est mis en oeuvre au Mexique depuis 2003. Il vise à protéger les forêts préservées et à avoir un impact social en rémunérant les communautés les plus

  10. [Trauma registry and injury].

    Science.gov (United States)

    Shapira, S C

    2001-10-01

    The trauma registry network constitutes an essential database in every injury prevention system. In order to rationally estimate the extent of injury in general, and injuries from traffic accidents in particular, the trauma registry systems should contain the most comprehensive and broad database possible, in line with the operational definitions. Ideally, the base of the injury pyramid should also include mild injuries and even "near-misses". The Israeli National Trauma Registry has come a long way in the last few years. The eventual inclusion of all trauma centers in Israel will enable the establishment of a firm base for the allocation of resources by decision-makers.

  11. Danish Hip Arthroscopy Registry

    DEFF Research Database (Denmark)

    Mygind-Klavsen, Bjarne; Grønbech Nielsen, Torsten; Maagaard, Niels

    2016-01-01

    Danish Hip Arthroscopy Registry (DHAR) was initiated in 2012 as a web-based prospective registry. The purpose of this study was to evaluate and report the epidemiologic and perioperative data of the first 2000 procedures in a Danish hip arthroscopy population and to describe the development of DHAR...... was 0.65 and HAGOS sub-scores were 51 (pain), 49 (symptoms), 53 (ADL), 35 (sport), 20 (physical activity) and 29, respectively. We conclude that patients undergoing hip arthroscopy report considerable pain, loss of function, reduced level of activity and reduced quality-of-life prior to surgery....... The problems with development and maintaining a large clinical registry are described and further studies are needed to validate data completeness. We consider the development of a national clinical registry for hip arthroscopy as a successful way of developing and maintaining a valuable clinical...

  12. 911 Master PSAP Registry

    Data.gov (United States)

    Federal Communications Commission — Updated as of 5Oct2017. The Registry lists PSAPs by an FCC assigned identification number, PSAP Name, State, County, City, and provides information on any type of...

  13. La Greffe de Peau dans le Traitement des Sequelles de la Main Brulee. A Propos de 152 Cas - Experience du Service de Chirurgie Plastique du Centre Hospitalier Universitaire Ibn-Sina, Rabat, Maroc

    Science.gov (United States)

    El Mazouz, S.; Fejjal, N.; Hafidi, J.; Cherkab, L.; Mejjati, H.; Belfqih, R.; Gharib, N.; Abbassi, A.

    2010-01-01

    Summary La main est fréquemment exposée aux brûlures, entraînant des séquelles esthétiques et fonctionnelles. Le traitement de ces séquelles est surtout chirurgical et consiste en la greffe de peau, dont le type dépend de la localisation de la brûlure et du type des séquelles. Dans ce travail rétrospectif, nous rapportons une série de 152 cas de brûlures des mains colligés au service de chirurgie plastique du Centre Hospitalier Universitaire Ibn-Sina de Rabat sur une période de dix ans, allant de 1998 à 2007. Les indications thérapeutiques dépendent du type de séquelles et de la localisation de la brûlure. En tout, 97 patients ont bénéficié d'une greffe cutanée, dont 76% par greffe de peau totale, 21% par greffe de peau demi-épaisse et 3% par peau fine. Les séquelles des brûlures des mains posent un problème thérapeutique majeur, malgré la diversité des procédés chirurgicaux, d'où l'intérêt de la prévention. PMID:21991196

  14. CAS School in Germany

    CERN Multimedia

    CERN Accelerator School

    The CERN Accelerator School (CAS), the Helmholtz Centre for Heavy Ion Research GmbH (GSI) and the Technische Universität Darmstadt (TU Darmstadt) jointly organised a course on General Accelerator Physics, at intermediate level, at TU Darmstadt from 27 September to 9 October 2009.   Participants in the CERN Accelerator School in Darmstadt, Germany. The Intermediate-level course followed established practice, with lectures on core topics in the mornings and specialised courses in the afternoons. The latter provided "hands-on" education and experience in the three selected topics: "RF Measurement Techniques", "Beam Instrumentation and Diagnostics" and "Optics Design and Correction". These proved to be highly successful, with participants choosing one course and following the topic throughout the school. Guided studies, tutorials, seminars and a poster session completed the programme. A visit to GSI and the F...

  15. 42 CFR 483.156 - Registry of nurse aides.

    Science.gov (United States)

    2010-10-01

    ... the registry because they have performed no nursing or nursing-related services for a period of 24... individual was found not guilty in a court of law, or the State is notified of the individual's death. (2) The registry must remove entries for individuals who have performed no nursing or nursing-related...

  16. Current situation and challenge of registry in China.

    Science.gov (United States)

    Zhang, Yang; Feng, Yuji; Qu, Zhi; Qi, Yali; Zhan, Siyan

    2014-09-01

    Increasing emphasis has been placed on registries for an organized system used in developing clinical research to improve health care. China has sufficient data that can be applied broadly, but the heterogeneity and irregularity of registries limit their applicability. This article aims to describe the status of registries in China and the related challenges. Patient registries for observational studies were retrieved from the International Clinical Trials Registry to quantitatively evaluate the number of comparatively high-quality registries in China. A literature search was also performed to provide support and updates. A total of 64 patient registries were retrieved from ClinicalTrials.gov using disease, product, and health service as criteria. The sample sizes ranged from 15 to 30,400, with only 12 registries marked as completed. This article describes and compares the detailed information in many aspects. The efficient use of registries has already made considerable progress in China; however, registries still require standardization, high-quality transition, and coordinated development.

  17. The Danish Heart Registry

    DEFF Research Database (Denmark)

    Özcan, Cengiz; Juel, Knud; Lassen, Jens Flensted

    2016-01-01

    AIM: The Danish Heart Registry (DHR) seeks to monitor nationwide activity and quality of invasive diagnostic and treatment strategies in patients with ischemic heart disease as well as valvular heart disease and to provide data for research. STUDY POPULATION: All adult (≥15 years) patients...... undergoing coronary angiography (CAG), percutaneous coronary intervention (PCI), coronary artery bypass grafting, and heart valve surgery performed across all Danish hospitals were included. MAIN VARIABLES: The DHR contains a subset of the data stored in the Eastern and Western Denmark Heart Registries (EDHR...

  18. The Western Denmark Heart Registry

    DEFF Research Database (Denmark)

    Schmidt, Morten; Maeng, Michael; Madsen, Morten

    2018-01-01

    The WDHR (Western Denmark Heart Registry) is a seminational, multicenter-based registry with longitudinal registration of detailed patient and procedure data since 1999. The registry includes as of January 1, 2017 approximately 240,000 coronary angiographies, 90,000 percutaneous coronary interven......The WDHR (Western Denmark Heart Registry) is a seminational, multicenter-based registry with longitudinal registration of detailed patient and procedure data since 1999. The registry includes as of January 1, 2017 approximately 240,000 coronary angiographies, 90,000 percutaneous coronary...

  19. Cancer Registry Data

    Centers for Disease Control (CDC) Podcasts

    2017-05-24

    Dr. Loria Pollack, a Senior Medical Epidemiologist, talks about the importance of cancer registry data to understanding how cancer affects the United States–now and in the future.  Created: 5/24/2017 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 5/24/2017.

  20. Danish Hip Arthroscopy Registry

    DEFF Research Database (Denmark)

    Mygind-Klavsen, Bjarne; Lund, Bent; Nielsen, Torsten Grønbech

    2018-01-01

    PURPOSE: Predictors of outcome after femoroacetabular impingement (FAI) surgery are not well-documented. This study presents data from the Danish Hip Arthroscopy Registry (DHAR) for such analyses. The purpose of this study was to identify predictors of poor outcome after FAI surgery in a Danish FAI...

  1. The Danish Twin Registry

    DEFF Research Database (Denmark)

    Skytthe, Axel; Ohm Kyvik, Kirsten; Vilstrup Holm, Niels

    2011-01-01

    Introduction: The Danish Twin Registry is a unique source for studies of genetic, familial and environmental factors on life events, health conditions and diseases. Content: More than 85,000 twin pairs born 1870-2008 in Denmark. Validity and coverage: Four main ascertainment methods have been emp...

  2. Environmental Protection Agency (EPA) Facility Registry Service (FRS) Emergency Response (ER) Toxic Substances Control Act (TSCA) Facilities - Oil and Hazardous Materials

    Data.gov (United States)

    Department of Homeland Security — The purpose of this web feature service is to provide users with access to integrated facility information from FRS, limited to the subset of facilities that link to...

  3. The EuroMyositis registry

    DEFF Research Database (Denmark)

    Lilleker, James B; Vencovsky, Jiri; Wang, Guochun

    2018-01-01

    AIMS: The EuroMyositis Registry facilitates collaboration across the idiopathic inflammatory myopathy (IIM) research community. This inaugural report examines pooled Registry data. METHODS: Cross-sectional analysis of IIM cases from 11 countries was performed. Associations between clinical subtyp...

  4. The national dose registry of Canada

    International Nuclear Information System (INIS)

    1982-04-01

    In 1951, when the National Dosimetry Service was established by the Department of National Health and Welfare, a system of centralized records was created as an integral part of the new service. Over the last few years the dose record system has expanded in size and content, and improvements have been made in the physical methods of record storage. In addition to the 250 000 individual dose records from the National Dosimetry Service, the National Dose Registry now includes internal tritium and external doses from nuclear generating stations, and radon daughter exposures submitted by uranium mining companies. With the increase in the use of radiation in the medical, industrial and research fields, it is becoming more important to have a comprehensive and readily accessible centralized record system. The Canadian National Dose Registry is particularly suited for continuing health risk studies of radiation workers and provides a base for future epidemiological studies

  5. 41 CFR 102-33.440 - Who must report CAS cost and utilization data?

    Science.gov (United States)

    2010-07-01

    ...-MANAGEMENT OF GOVERNMENT AIRCRAFT Reporting Information on Government Aircraft Commercial Aviation Services... agencies, except the Armed Forces and U.S. intelligence agencies, must report CAS cost and utilization data...

  6. Corrélats des enquêtes conjointes des services de protection de l'enfance et des services de police sur les abus sexuels d'enfants : résultats de l'Étude canadienne sur l'incidence des signalements de cas de violence et de négligence envers les enfants 2008

    Directory of Open Access Journals (Sweden)

    L. Tonmyr

    2015-01-01

    Full Text Available Introduction : Dans cette étude, nous examinons la fréquence des enquêtes conjointes menées par les services de protection de l'enfance et les services de police dans les cas d'abus sexuels en comparaison des autres types de maltraitance. Nous examinons également les associations, dans les enquêtes conjointes, entre les caractéristiques relatives à l'enfant, celles relatives au pourvoyeur de soins de l'enfant, celles relatives aux mauvais traitements eux-mêmes et celles relatives à l'enquête, en nous intéressant plus particulièrement aux enquêtes sur les abus sexuels. Méthodologie : Nous avons analysé par régression logistique les données de l'Étude canadienne sur l'incidence des signalements de cas de violence et de négligence envers les enfants 2008. Résultats : D'après les données, les enquêtes conjointes portent en premier lieu sur les abus sexuels (55 %, puis sur la violence physique, la négligence et la violence psychologique. La corroboration des mauvais traitements, les mauvais traitements graves, le placement, l'intervention des tribunaux de la jeunesse et l'orientation d'un membre de la famille vers des services spécialisés sont plus fréquents quand les services de police participent à l'enquête. Conclusion : Cette étude vient bonifier l'information limitée dont on dispose sur les corrélats des enquêtes conjointes menées par les agences de protection de l'enfance et les services de police. D'autres recherches devront être effectuées pour déterminer l'efficacité de ces enquêtes conjointes.

  7. The Brazilian Twin Registry.

    Science.gov (United States)

    Ferreira, Paulo H; Oliveira, Vinicius C; Junqueira, Daniela R; Cisneros, Lígia C; Ferreira, Lucas C; Murphy, Kate; Ordoñana, Juan R; Hopper, John L; Teixeira-Salmela, Luci F

    2016-12-01

    The Brazilian Twin Registry (BTR) was established in 2013 and has impelled twin research in South America. The main aim of the initiative was to create a resource that would be accessible to the Brazilian scientific community as well as international researchers interested in the investigation of the contribution of genetic and environmental factors in the development of common diseases, phenotypes, and human behavior traits. The BTR is a joint effort between academic and governmental institutions from Brazil and Australia. The collaboration includes the Federal University of Minas Gerais (UFMG) in Brazil, the University of Sydney and University of Melbourne in Australia, the Australian Twin Registry, as well as the research foundations CNPq and CAPES in Brazil. The BTR is a member of the International Network of Twin Registries. Recruitment strategies used to register twins have been through participation in a longitudinal study investigating genetic and environmental factors for low back pain occurrence, and from a variety of sources including media campaigns and social networking. Currently, 291 twins are registered in the BTR, with data on demographics, zygosity, anthropometrics, and health history having been collected from 151 twins using a standardized self-reported questionnaire. Future BTR plans include the registration of thousands of Brazilian twins identified from different sources and collaborate nationally and internationally with other research groups interested on twin studies.

  8. L’usage politique de l’islam : l’universel au service d’un État. Le cas du Maroc The Political Use of Islam. The Universal in the Service of a State. The Moroccan Case

    Directory of Open Access Journals (Sweden)

    Abdessamad Belhaj

    2011-03-01

    Full Text Available Lorsqu’il s’agit d’étudier les rapports des pays arabes à la mondialisation, il est nécessaire d’évoquer l’islam. En tant que facteur local, la symbolique islamique offre des ressources de légitimation au pouvoir. Le cas marocain illustre bien la manière dont les rapports existant entre le Makhzen et le répertoire religieux (Amīr al-Mu’minīne, la bayca , la chérifibilité…  font de l’introduction de la modernité un simple espace virtuel et fonctionnel. L’émergence de la contestation islamiste participe à la consécration du répertoire traditionnel. D’autre part, depuis les trois dernières décennies, l’essor de l’islam mondialisé offre au Maroc des opportunités politiques à l’échelle mondiale. Ceci est observable au niveau du rôle joué par le pays dans le cadre de la diplomatie islamique (OCI, ISESCO…  ou au niveau de son positionnement dans l’islam européen. La gestion de l’interaction entre l’islam local et l’islam global, adaptée à la conjoncture internationale, assure le maintien au pouvoir du régime.One cannot study the relationships between Arab countries and globalization without taking Islam into account for it offers symbolic support to legitimizing local power. Morocco is a good example : the relations between the royal court (Makhzen and Islamic features such as being the Commander of the Faithful or Sheriffhood make of modernity a mere virtual or functional sphere. Even the emergence of Islamic contestation contributes to the consecration of the traditional repertory. On the other hand, the rise of world Islam during the last thirty years has opened up political opportunities for Morocco on the international stage – for instance the agencies of Islamic diplomacy (OCI, ISESCO or the quest for a new role in European Islam. By managing the interaction between the local and the global, the regime is able to keep itself in power.

  9. L’optimisation juridique du paiement pour services environnementaux en faveur de la préservation des services environnementaux : le cas du Cameroun et de la République Démocratique du Congo

    Directory of Open Access Journals (Sweden)

    Blaise-Pascal Ntirumenyerwa Mihigo

    2017-02-01

    Full Text Available The study starts from a hypothesis on the coherence and compatibility of the legal instruments in force in Cameroon and in the Democratic Republic of Congo (DRC with the optimization of payment for environmental services (PES and the preservation of environmental services. This study has employed a legal approach and interviews in order to investigate whether there is coherence and compatibility or not between the two variables of this hypothesis: (1 the legal instruments in force in Cameroon and in the DRC and (2 the optimization of PES and the preservation of environmental services. This study consists of three parts. The first part deals with the theoretical framework of PES and the place of PES in the legal order. In this first part, the definition of an optimal PES, the indicators of an optimal PES and the categories of legal frameworks on PES have been revealed. These are the fundamental elements to conduct a systematic analysis in the second and third parts. Based on these fundamental elements, the study analyses the legal instru- ments from international, regional (Africa and domestic (Cameroon and the DRC levels and investigates through field research two PES projects, one in Cameroon called “PES comminatory project” and another in the DRC called “REDD CBFF-Luki” respectively in the second and the third parts. From the analysis of these legal instruments and the investigation of these two PES projects, it has become apparent that there is a lack of coherence and compatibility between the legal instruments and these two PES projects in Cameroon and in the DRC, and the optimization of PES and the preservation of environmental services in the Congo Basin in general, especially in these two States. Useful recommendations have been made to eradicate these shortcomings. Key words: payment for environmental services, environmental services, Congo Basin

  10. The Danish Schizophrenia Registry

    DEFF Research Database (Denmark)

    Baandrup, Lone; Cerqueira, Charlotte; Haller, Lea

    2016-01-01

    Aim of database: To systematically monitor and improve the quality of treatment and care of patients with schizophrenia in Denmark. In addition, the database is accessible as a resource for research. Study population: Patients diagnosed with schizophrenia and receiving mental health care...... to the data for use in specific research projects by applying to the steering committee. Conclusion: The Danish Schizophrenia Registry represents a valuable source of informative data to monitor and improve the quality of care of patients with schizophrenia in Denmark. However, continuous resources and time...

  11. eRegistries: Electronic registries for maternal and child health.

    Science.gov (United States)

    Frøen, J Frederik; Myhre, Sonja L; Frost, Michael J; Chou, Doris; Mehl, Garrett; Say, Lale; Cheng, Socheat; Fjeldheim, Ingvild; Friberg, Ingrid K; French, Steve; Jani, Jagrati V; Kaye, Jane; Lewis, John; Lunde, Ane; Mørkrid, Kjersti; Nankabirwa, Victoria; Nyanchoka, Linda; Stone, Hollie; Venkateswaran, Mahima; Wojcieszek, Aleena M; Temmerman, Marleen; Flenady, Vicki J

    2016-01-19

    The Global Roadmap for Health Measurement and Accountability sees integrated systems for health information as key to obtaining seamless, sustainable, and secure information exchanges at all levels of health systems. The Global Strategy for Women's, Children's and Adolescent's Health aims to achieve a continuum of quality of care with effective coverage of interventions. The WHO and World Bank recommend that countries focus on intervention coverage to monitor programs and progress for universal health coverage. Electronic health registries - eRegistries - represent integrated systems that secure a triple return on investments: First, effective single data collection for health workers to seamlessly follow individuals along the continuum of care and across disconnected cadres of care providers. Second, real-time public health surveillance and monitoring of intervention coverage, and third, feedback of information to individuals, care providers and the public for transparent accountability. This series on eRegistries presents frameworks and tools to facilitate the development and secure operation of eRegistries for maternal and child health. In this first paper of the eRegistries Series we have used WHO frameworks and taxonomy to map how eRegistries can support commonly used electronic and mobile applications to alleviate health systems constraints in maternal and child health. A web-based survey of public health officials in 64 low- and middle-income countries, and a systematic search of literature from 2005-2015, aimed to assess country capacities by the current status, quality and use of data in reproductive health registries. eRegistries can offer support for the 12 most commonly used electronic and mobile applications for health. Countries are implementing health registries in various forms, the majority in transition from paper-based data collection to electronic systems, but very few have eRegistries that can act as an integrating backbone for health

  12. Spacer capture and integration by a type I-F Cas1-Cas2-3 CRISPR adaptation complex.

    Science.gov (United States)

    Fagerlund, Robert D; Wilkinson, Max E; Klykov, Oleg; Barendregt, Arjan; Pearce, F Grant; Kieper, Sebastian N; Maxwell, Howard W R; Capolupo, Angela; Heck, Albert J R; Krause, Kurt L; Bostina, Mihnea; Scheltema, Richard A; Staals, Raymond H J; Fineran, Peter C

    2017-06-27

    CRISPR-Cas adaptive immune systems capture DNA fragments from invading bacteriophages and plasmids and integrate them as spacers into bacterial CRISPR arrays. In type I-E and II-A CRISPR-Cas systems, this adaptation process is driven by Cas1-Cas2 complexes. Type I-F systems, however, contain a unique fusion of Cas2, with the type I effector helicase and nuclease for invader destruction, Cas3. By using biochemical, structural, and biophysical methods, we present a structural model of the 400-kDa Cas1 4 -Cas2-3 2 complex from Pectobacterium atrosepticum with bound protospacer substrate DNA. Two Cas1 dimers assemble on a Cas2 domain dimeric core, which is flanked by two Cas3 domains forming a groove where the protospacer binds to Cas1-Cas2. We developed a sensitive in vitro assay and demonstrated that Cas1-Cas2-3 catalyzed spacer integration into CRISPR arrays. The integrase domain of Cas1 was necessary, whereas integration was independent of the helicase or nuclease activities of Cas3. Integration required at least partially duplex protospacers with free 3'-OH groups, and leader-proximal integration was stimulated by integration host factor. In a coupled capture and integration assay, Cas1-Cas2-3 processed and integrated protospacers independent of Cas3 activity. These results provide insight into the structure of protospacer-bound type I Cas1-Cas2-3 adaptation complexes and their integration mechanism.

  13. Expanding CRISPR/Cas9 Genome Editing Capacity in Zebrafish Using SaCas9

    OpenAIRE

    Feng, Yan; Chen, Cheng; Han, Yuxiang; Chen, Zelin; Lu, Xiaochan; Liang, Fang; Li, Song; Qin, Wei; Lin, Shuo

    2016-01-01

    The type II CRISPR/Cas9 system has been used widely for genome editing in zebrafish. However, the requirement for the 5′-NGG-3′ protospacer-adjacent motif (PAM) of Cas9 from Streptococcus pyogenes (SpCas9) limits its targeting sequences. Here, we report that a Cas9 ortholog from Staphylococcus aureus (SaCas9), and its KKH variant, successfully induced targeted mutagenesis with high frequency in zebrafish. Confirming previous findings, the SpCas9 variant, VQR, can also induce targeted mutation...

  14. Danish National Lymphoma Registry

    DEFF Research Database (Denmark)

    Arboe, Bente; Josefsson, Pär; Jørgensen, Judit

    2016-01-01

    AIM OF DATABASE: The Danish National Lymphoma Registry (LYFO) was established in order to monitor and improve the diagnostic evaluation and the quality of treatment of all lymphoma patients in Denmark. STUDY POPULATION: The LYFO database was established in 1982 as a seminational database including...... all lymphoma patients referred to the departments of hematology. The database became nationwide on January 1, 2000. MAIN VARIABLES: The main variables include both clinical and paraclinical variables as well as details of treatment and treatment evaluation. Up to four forms are completed for each......-100 years) and a male/female ratio of 1.23:1. Patients can be registered with any of 42 different subtypes according to the World Health Organization classifications. CONCLUSION: LYFO is a nationwide database for all lymphoma patients in Denmark and includes detailed information. This information is used...

  15. Danish Prostate Cancer Registry

    DEFF Research Database (Denmark)

    Helgstrand, J Thomas; Klemann, Nina; Røder, Martin Andreas

    2016-01-01

    of SNOMED codes were identified. A computer algorithm was developed to transcode SNOMED codes into an analyzable format including procedure (eg, biopsy, transurethral resection, etc), diagnosis, and date of diagnosis. For validation, ~55,000 pathological reports were manually reviewed. Prostate-specific...... antigen, vital status, causes of death, and tumor-node-metastasis classification were integrated from national registries. RESULTS: Of the 161,525 specimens from 113,801 males identified, 83,379 (51.6%) were sets of prostate biopsies, 56,118 (34.7%) were transurethral/transvesical resections......BACKGROUND: Systematized Nomenclature of Medicine (SNOMED) codes are computer-processable medical terms used to describe histopathological evaluations. SNOMED codes are not readily usable for analysis. We invented an algorithm that converts prostate SNOMED codes into an analyzable format. We...

  16. Pediatric Clinical Trials Conducted in South Korea from 2006 to 2015: An Analysis of the South Korean Clinical Research Information Service, US ClinicalTrials.gov and European Clinical Trials Registries.

    Science.gov (United States)

    Choi, Sheung-Nyoung; Lee, Ji-Hyun; Song, In-Kyung; Kim, Eun-Hee; Kim, Jin-Tae; Kim, Hee-Soo

    2017-12-01

    The status of pediatric clinical trials performed in South Korea in the last decade, including clinical trials of drugs with unapproved indications for children, has not been previously examined. The aim was to provide information regarding the current state of pediatric clinical trials and create a basis for future trials performed in South Korea by reviewing three databases of clinical trials registrations. We searched for pediatric clinical studies (participants South Korea between 2006 and 2015 registered on the Clinical Research Information Service (CRIS), ClinicalTrials.gov, and the European Clinical Trials Registry (EuCTR). Additionally, we reviewed whether unapproved indications were involved in each trial by comparing the trials with a list of authorized trials provided by the Ministry of Food and Drug Safety (MFDS). The primary and secondary outcomes were to determine the change in number of pediatric clinical trials with unapproved indications over time and to assess the status of unauthorized pediatric clinical trials from the MFDS and the publication of articles after these clinical trials, respectively. We identified 342 clinical studies registered in the CRIS (n = 81), ClinicalTrials.gov (n = 225), and EuCTR (n = 36), of which 306 were reviewed after excluding duplicate registrations. Among them, 181 studies were interventional trials dealing with drugs and biological agents, of which 129 (71.3%) involved unapproved drugs. Of these 129 trials, 107 (82.9%) were authorized by the MFDS. Pediatric clinical trials in South Korea aiming to establish the safety and efficacy of drugs in children are increasing; however, non-MFDS-authorized studies remain an issue.

  17. Les tuberculomes intracraniens: à propos de 125 cas

    Science.gov (United States)

    Moufid, Faycal; Oulali, Noureddine; El Fatemi, Nizare; Gana, Rachid; Maaqili, Rachid; Bellakhdar, Fouad

    2012-01-01

    Les tuberculomes intracrâniens représentent l'une des localisations les plus graves de la tuberculose, leur incidence varie en fonction du contexte représentant 0,2% des processus intracrâniens dans les pays occidentaux et 5 à 10% des masses intracrâniennes dans les pays en voie de développement. Nous rapportons une étude rétrospective de 125 cas. L'hypertension intracrânienne (45%) et le déficit neurologique (36%) sont les signes cliniques les plus fréquents. La lésion était localisée dans 60% des cas en sus-tentoriel et dans 40% des cas en sous-tentoriel. L'approche thérapeutique a consisté en un abord direct du tuberculome dans 67 cas (53%), une biopsie stéréotaxique dans 32 cas (25%), le traitement médical en première intention sans confirmation histologique dans 26 cas (20%). Avant 1993 notre service ne disposait pas de cadre de stéréotaxie, notre attitude thérapeutique consistait soit en un abord direct de la lésion dans 70% des cas, soit un traitement antituberculeux en première intention sans confirmation histologique (30%). Cette attitude était corrélée à une mortalité et morbidité non négligeables respectivement 3% et 10%. Après 1993; le taux d'abords direct a chuté a 38%, avec 47% de biopsies stéréotaxiques et seulement 13% des patients traités par antibacillaires sans preuve histologique. Ceci s'est accompagné d'une réduction significative de mortalité a 1,4% (p = 0,0003) et de morbidité a 2% (p = 0,0027). PMID:22937196

  18. EPA Facility Registry Service (FRS): Power Plants

    Data.gov (United States)

    U.S. Environmental Protection Agency — This GIS dataset contains data on power plants, based on the Energy Information Administration's EIA-860 dataset and supplemented with data from EPA's Facility...

  19. EPA Facility Registry Service (FRS): CERCLIS

    Data.gov (United States)

    U.S. Environmental Protection Agency — This data provides location and attribute information on Facilities regulated under the Comprehensive Environmental Responsibility Compensation and Liability...

  20. Danish Hip Arthroscopy Registry (DHAR)

    DEFF Research Database (Denmark)

    Lund, Bent; Mygind-Klavsen, Bjarne; Grønbech Nielsen, Torsten

    2017-01-01

    The Danish Hip Arthroscopy Registry (DHAR) was initiated in January 2012 as a web-based prospective registry. The purpose of this study was to evaluate and report the first registry based outcome data of a national population with radiological and clinical femoroacetabular impingement (FAI......) data from DHAR between January 2012 and November 2015 were extracted. Radiological pincer-type FAI was defined as LCE > 35° and cam FAI as alpha-angle > 55°. These data were combined with FAI surgical data such as osteochondroplasty and labral repair or resection. PROMs consisting of HAGOS, EQ-5 D...

  1. Embedded Fragments Registry (EFR)

    Data.gov (United States)

    Department of Veterans Affairs — In 2009, the Department of Defense estimated that approximately 40,000 service members who served in OEF/OIF may have embedded fragment wounds as the result of small...

  2. Semiotic and discursive variables in cas-based didactical engineering

    DEFF Research Database (Denmark)

    Winsløw, Carl

    2003-01-01

    CAS, didactical engeneering, Maple, semiotics, undergraduate teaching, mathematics, education, didactics......CAS, didactical engeneering, Maple, semiotics, undergraduate teaching, mathematics, education, didactics...

  3. CRISPR-Cas: Adapting to change.

    Science.gov (United States)

    Jackson, Simon A; McKenzie, Rebecca E; Fagerlund, Robert D; Kieper, Sebastian N; Fineran, Peter C; Brouns, Stan J J

    2017-04-07

    Bacteria and archaea are engaged in a constant arms race to defend against the ever-present threats of viruses and invasion by mobile genetic elements. The most flexible weapons in the prokaryotic defense arsenal are the CRISPR-Cas adaptive immune systems. These systems are capable of selective identification and neutralization of foreign DNA and/or RNA. CRISPR-Cas systems rely on stored genetic memories to facilitate target recognition. Thus, to keep pace with a changing pool of hostile invaders, the CRISPR memory banks must be regularly updated with new information through a process termed CRISPR adaptation. In this Review, we outline the recent advances in our understanding of the molecular mechanisms governing CRISPR adaptation. Specifically, the conserved protein machinery Cas1-Cas2 is the cornerstone of adaptive immunity in a range of diverse CRISPR-Cas systems. Copyright © 2017, American Association for the Advancement of Science.

  4. Using CRISPR-Cas systems as antimicrobials.

    Science.gov (United States)

    Bikard, David; Barrangou, Rodolphe

    2017-06-01

    Although CRISPR-Cas systems naturally evolved to provide adaptive immunity in bacteria and archaea, Cas nucleases can be co-opted to target chromosomal sequences rather than invasive genetic elements. Although genome editing is the primary outcome of self-targeting using CRISPR-based technologies in eukaryotes, self-targeting by CRISPR is typically lethal in bacteria. Here, we discuss how DNA damage introduced by Cas nucleases in bacteria can efficiently and specifically lead to plasmid curing or drive cell death. Specifically, we discuss how various CRISPR-Cas systems can be engineered and delivered using phages or phagemids as vectors. These principles establish CRISPR-Cas systems as potent and programmable antimicrobials, and open new avenues for the development of CRISPR-based tools for selective removal of bacterial pathogens and precise microbiome composition alteration. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. CasA mediates Cas3-catalyzed target degradation during CRISPR RNA-guided interference.

    Science.gov (United States)

    Hochstrasser, Megan L; Taylor, David W; Bhat, Prashant; Guegler, Chantal K; Sternberg, Samuel H; Nogales, Eva; Doudna, Jennifer A

    2014-05-06

    In bacteria, the clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) DNA-targeting complex Cascade (CRISPR-associated complex for antiviral defense) uses CRISPR RNA (crRNA) guides to bind complementary DNA targets at sites adjacent to a trinucleotide signature sequence called the protospacer adjacent motif (PAM). The Cascade complex then recruits Cas3, a nuclease-helicase that catalyzes unwinding and cleavage of foreign double-stranded DNA (dsDNA) bearing a sequence matching that of the crRNA. Cascade comprises the CasA-E proteins and one crRNA, forming a structure that binds and unwinds dsDNA to form an R loop in which the target strand of the DNA base pairs with the 32-nt RNA guide sequence. Single-particle electron microscopy reconstructions of dsDNA-bound Cascade with and without Cas3 reveal that Cascade positions the PAM-proximal end of the DNA duplex at the CasA subunit and near the site of Cas3 association. The finding that the DNA target and Cas3 colocalize with CasA implicates this subunit in a key target-validation step during DNA interference. We show biochemically that base pairing of the PAM region is unnecessary for target binding but critical for Cas3-mediated degradation. In addition, the L1 loop of CasA, previously implicated in PAM recognition, is essential for Cas3 activation following target binding by Cascade. Together, these data show that the CasA subunit of Cascade functions as an essential partner of Cas3 by recognizing DNA target sites and positioning Cas3 adjacent to the PAM to ensure cleavage.

  6. Achieving a milestone: AMOR is now archived in Portico and indexed in CAS

    Directory of Open Access Journals (Sweden)

    R.N Sugitha Nadarajah

    2016-10-01

    Full Text Available The journal of Advances in Modern Oncology Research (AMOR is proud to announce its partnership with Portico, a leading digital preservation service provider, to ensure the long term accessibility of its published contents. In addition, it is now indexed by the gold standard of chemical information database Chemical Abstracts Services (CAS after publishing only six bimonthly issues, dating back to October 2015. AMOR’s Editor-in-Chief Dr. Omar Abdel-Rahman proudly shares: “Our vision is to be far more than just a journal, we want to be a platform that publishes high quality cancer research contents from all over the world. I think we are progressing, at an acceptable pace, in that direction."The Portico archive is a “centralized repository of tens of thousands of e-journals, e-books, and other electronic content, replicated to ensure security,” according to the registry organization. “Content comes into the archive under formal preservation agreements with publishers. Content providers submit source files to Portico, and we repackage these source files into an archival format and provide long-term archival management and format migration as needed. Our approach is driven by our commitment to meeting clear preservation goals,” it states. AMOR’s Managing Editor Dr. TS Jong, when asked to comment about the impact of this development, adds: “AMOR is committed towards meeting the highest international publication standards and as such, has a clear archiving and indexing roadmap to sustain our growth. The journal acknowledges the importance of ensuring the continuous accessibility of our published articles in multiple repositories. Therefore, we are delighted with the recent partnership between AMOR and Portico, a well-known third-party repository service provider, to safeguard the long-term availability of our contents.”Archiving AMOR’s articles within Portico ensures that the materials published are always available for access. In

  7. Review of patient registries in dermatology.

    Science.gov (United States)

    DiMarco, Gabriella; Hill, Dane; Feldman, Steven R

    2016-10-01

    Patient registries are datasets containing information on patients with a particular disease or patients who are undergoing a specific treatment. Our objective was to search for and catalog the types of registries being used in dermatology and investigate their characteristics and uses. We searched Google, the Registry of Patient Registries, Orphanet, and ClinicalTrials.gov to compile a list of dermatology disease registries. We also conducted a literature review on the uses of dermatology registries using PubMed. We identified 48 dermatology patient registries, with 23 distinct diseases represented. We also identified 11 registries used for postmarketing surveillance of skin disease. Our search was limited to registries in English. Registries are commonly used for the study of rare dermatologic diseases and for postsurveillance monitoring of systemic therapies in more common dermatologic diseases, such as psoriasis. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  8. [Detection of CRSPR-Cas system in Streptococcus thermophiles].

    Science.gov (United States)

    Li, Wan; Liang, Hongzhang; Zhang, Danqing; Wang, Nana; Tang, Yaru; Li, Bailiang; Huo, Guicheng

    2016-04-14

    We aimed to detect the CRSPR-Cas system of six Streptococcus thermophilus. Bioinformatics method was used to predict CRSPR-Cas system of nine S. thermophilus that published in National Center for Biotechnology Information. Four primers were designed according to the flanking sequences of standard strains and the CRISPR-Cas system of six S. thermophilus have been detected by PCR method. S. thermophilus S4 had a Cas9 gene, others all had Cas9 gene, Cas10 gene and Cas9* gene. In addition, 79 and KLDS3.0207 still had Cas3 gene. Signature genes amplification of CRSPR-Cas system could predict the type of CRSPR-Cas system in unsequenced strains, these findings will help establish the foundation for the study of CRSPR-Cas system in lactic acid bacteria.

  9. 78 FR 54956 - Agency Information Collection (Open Burn Pit Registry Airborne Hazard Self-Assessment...

    Science.gov (United States)

    2013-09-06

    ...: Open Burn Pit Registry Airborne Hazard Self-Assessment Questionnaire, VA Form 10-10066. Type of Review... services to Open Burn Pit Registry participants and improve VA's ability to understand the health effects... DEPARTMENT OF VETERANS AFFAIRS [OMB Control No. 2900-NEW] Agency Information Collection (Open Burn...

  10. 78 FR 44625 - Proposed Information Collection (Open Burn Pit Registry Airborne Hazard Self-Assessment...

    Science.gov (United States)

    2013-07-24

    ... DEPARTMENT OF VETERANS AFFAIRS Proposed Information Collection (Open Burn Pit Registry Airborne... to ``OMB Control No. 2900--NEW, Open Burn Pit Registry Airborne Hazard Self-Assessment Questionnaire... health effects of service members' exposure to toxic airborne chemicals and fumes caused by open burn...

  11. Modification of CAS-protocol for improvement of security web-applications from unauthorized access

    Directory of Open Access Journals (Sweden)

    Alexey I Igorevich Alexandrov

    2017-07-01

    Full Text Available Dissemination of information technologies and the expansion of their application demand constantly increasing security level for users, operating with confidential information and personal data. The problem of setting up secure user identification is probably one of the most common tasks, which occur in the process of software development. Today, despite the availability of a large amount of authentication tools, new solutions, mechanisms and technologies are being introduced regularly. Primarily, it is done to increase the security level of data protection against unauthorized access. This article describes the experience of using central user authentication service based on CAS-protocol (CAS – Central Authentication Service and free open source software, analyzing its main advantages and disadvantages and describing the possibility of its modification, which would increase security of web-based information systems from being accessed illegally. The article contains recommendations for setting a maximum time limit for users working on services, integrated with central authentication; and, analyses the research of implementing modern web-technologies while using user authentication system based on CAS-protocol. In addition, it describes the ways of CAS-server modernization for developing additional modules: a module for collecting and analyzing the use of information systems, and another one, for a user management system. Furthermore, CAS-protocol can be used at universities and other organizations for creating a unified information environment in education.

  12. Fragmentation of the CRISPR-Cas Type I-B signature protein Cas8b.

    Science.gov (United States)

    Richter, Hagen; Rompf, Judith; Wiegel, Julia; Rau, Kristina; Randau, Lennart

    2017-11-01

    CRISPR arrays are transcribed into long precursor RNA species, which are further processed into mature CRISPR RNAs (crRNAs). Cas proteins utilize these crRNAs, which contain spacer sequences that can be derived from mobile genetic elements, to mediate immunity during a reoccurring virus infection. Type I CRISPR-Cas systems are defined by the presence of different Cascade interference complexes containing large and small subunits that play major roles during target DNA selection. Here, we produce the protein and crRNA components of the Type I-B CRISPR-Cas complex of Clostridium thermocellum and Methanococcus maripaludis. The C. thermocellum Cascade complexes were reconstituted and analyzed via size-exclusion chromatography. Activity of the heterologous M. maripaludis CRISPR-Cas system was followed using phage lambda plaques assays. The reconstituted Type-I-B Cascade complex contains Cas7, Cas5, Cas6b and the large subunit Cas8b. Cas6b can be omitted from the reconstitution protocol. The large subunit Cas8b was found to be represented by two tightly associated protein fragments and a small C-terminal Cas8b segment was identified in recombinant complexes and C. thermocellum cell lysate. Production of Cas8b generates a small C-terminal fragment, which is suggested to fulfill the role of the missing small subunit. A heterologous, synthetic M. maripaludis Type I-B system is active in E. coli against phage lambda, highlighting a potential for genome editing using endogenous Type-I-B CRISPR-Cas machineries. This article is part of a Special Issue entitled "Biochemistry of Synthetic Biology - Recent Developments" Guest Editor: Dr. Ilka Heinemann and Dr. Patrick O'Donoghue. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. CAS at the Cockcroft Institute

    CERN Multimedia

    2007-01-01

    The CERN Accelerator School (CAS) and the UK’s new centre for accelerator science, the Cockcroft Institute, jointly organised a course on General Accelerator Physics, at intermediate level, at the Cockcroft Institute, Daresbury, UK, from 16 to 28 September 2007. The venue took advantage of the excellent new facilities in the Institute and the existing infrastructure of the adjacent Daresbury Laboratory. The intermediate level course followed established practice, with lectures on core topics in the mornings and specialised courses in the afternoons. The latter provided "hands-on" education and experience in the three selected topics: "RF Measurements Techniques", "Beam Instrumentation and Diagnostics" and "Optics Design and Correction". These proved to be highly successful, with participants choosing one course and following the topic throughout the school. Guided studies, tutorials, seminars and a poster session completed the prog...

  14. The value of trauma registries.

    Science.gov (United States)

    Moore, Lynne; Clark, David E

    2008-06-01

    Trauma registries are databases that document acute care delivered to patients hospitalised with injuries. They are designed to provide information that can be used to improve the efficiency and quality of trauma care. Indeed, the combination of trauma registry data at regional or national levels can produce very large databases that allow unprecedented opportunities for the evaluation of patient outcomes and inter-hospital comparisons. However, the creation and upkeep of trauma registries requires a substantial investment of money, time and effort, data quality is an important challenge and aggregated trauma data sets rarely represent a population-based sample of trauma. In addition, trauma hospitalisations are already routinely documented in administrative hospital discharge databases. The present review aims to provide evidence that trauma registry data can be used to improve the care dispensed to victims of injury in ways that could not be achieved with information from administrative databases alone. In addition, we will define the structure and purpose of contemporary trauma registries, acknowledge their limitations, and discuss possible ways to make them more useful.

  15. Méningiome intracrânien multiple: expérience du service de neurochirurgie CHU Avicenne Rabat - Salé, à propos de 4 cas et revue de la literature

    Science.gov (United States)

    Djoubairou, Ben Ousmanou; Karekezi, Claire; Moussé, Nabil; Doleagbenou, Agbéko Komlan; Gana, Rachid; El Abbadi, Najia; El Maaqili, Moulay Rachid

    2014-01-01

    Les méningiomes intracrâniennes multiples sont définies comme la présence d'au moins deux méningiomes sur des sites intracrâniens différents et ceci en absence de neurofibromatose. C'est une tumeur rare dont la prévalence varie entre 1-10%. Le but de notre travail était de décrire les caractéristiques cliniques, radiologiques, histologiques d'une série de 4 patients porteurs de méningiome multiple et en déduire les facteurs de risques de survenue de cette pathologie. Préciser la qualité d'exérèse chirurgicale de la lésion selon la classification de Simpson. Rapporter les suites postopératoires ainsi que le suivie à long termes des patients afin de préciser leur qualité de vie. Il s'agit d'une étude rétrospective portant sur 4 cas de Méningiomes intracrâniens multiples sur 174 patients opérés pour méningiome au CHU Avicenne entre Janvier 2000 à Décembre 2013. En s'aidant des données cliniques, imageries, chirurgicales, histologiques mentionnée dans le dossier médical de chaque patient. Notre série est constitué de 4 patients (3 femmes pour 1 homme), d'un âge allant de 42-50 ans (moyenne d’âge= 45,5 ans). Nous avons identifié 21 méningiomes (17 en sus tentoriel et 4 en sous tentoriel), aucun cas de décès ni d'infection postopératoire dans notre échantillon. Le pronostic reste bon malgré le nombre de lésion nécessitant parfois plusieurs interventions chirurgicales. PMID:25419331

  16. Danish Hip Arthroscopy Registry (DHAR)

    DEFF Research Database (Denmark)

    Lund, Bent; Mygind-Klavsen, Bjarne; Grønbech Nielsen, Torsten

    2017-01-01

    The Danish Hip Arthroscopy Registry (DHAR) was initiated in January 2012 as a web-based prospective registry. The purpose of this study was to evaluate and report the first registry based outcome data of a national population with radiological and clinical femoroacetabular impingement (FAI......) undergoing hip arthroscopic treatment. Our primary hypothesis was that patients undergoing hip arthroscopy would improve significantly in pain, quality of life and sports related outcome measurements in Patient Related Outcome Measures (PROM). Peri-operative data and Patient Reported Outcome Measures (PROM......-5 D demonstrated improvement after 1 and 2 years from 0.66 pre-op to 0.78 at 2 years. HSAS improved significantly from 2.5 to 3.3. Pain score data demonstrated improvement in NRS-rest 39 to 17 and NRS Walk 49 to 22 at follow-up. We conclude that patients with FAI undergoing hip arthroscopy...

  17. A need for national registry of radiation workers

    International Nuclear Information System (INIS)

    Marathe, P.K.; Krishnan, D.; Massand, O.P.; Dhond, R.V.

    1988-01-01

    In India about 33000 radiation workers are monitored regularly from a centralised Personnel Monitoring Service conducted by the Division of Radiological Protection, B.A.R.C. In view of the large dose data accumulated over the past thirty years it is only logical to investigate for biological effects if any. The need to initiate National Registry of Radiation Workers (NRRW) is pointed out. Such a registry is in force in U.K., Canada, France and Japan etc. Even in case of negative findings, such an exercise would help in allaying fears among radiation workers in particular and the public in general. (author)

  18. Pre-hospital electrocardiogram triage with tele-cardiology support is associated with shorter time-to-balloon and higher rates of timely reperfusion even in rural areas: data from the Bari- Barletta/Andria/Trani public emergency medical service 118 registry on primary angioplasty in ST-elevation myocardial infarction.

    Science.gov (United States)

    Brunetti, Natale Daniele; Di Pietro, Gaetano; Aquilino, Ambrogio; Bruno, Angela I; Dellegrottaglie, Giulia; Di Giuseppe, Giuseppe; Lopriore, Claudio; De Gennaro, Luisa; Lanzone, Saverio; Caldarola, Pasquale; Antonelli, Gianfranco; Di Biase, Matteo

    2014-09-01

    We report the preliminary data from a regional registry on ST-elevation myocardial infarction (STEMI) patients treated with primary angioplasty in Apulia, Italy; the region is covered by a single public health-care service, a single public emergency medical service (EMS), and a single tele-medicine service provider. Two hundred and ninety-seven consecutive patients with STEMI transferred by regional free public EMS 1-1-8 for primary-PCI were enrolled in the study; 123 underwent pre-hospital electrocardiograms (ECGs) triage by tele-cardiology support and directly referred for primary-PCI, those remaining were just transferred by 1-1-8 ambulances for primary percutaneous coronary intervention (PCI) (diagnosis not based on tele-medicine ECG; already hospitalised patients, emergency-room without tele-medicine support). Time from first ECG diagnostic for STEMI to balloon was recorded; a time-to-balloon primary-PCI). Pre-hospital triage with tele-cardiology ECG in an EMS registry from an area with more than one and a half million inhabitants was associated with shorter time-to-balloon and higher rates of timely treated patients, even in 'rural' areas. © The European Society of Cardiology 2014.

  19. The Toxicology Investigators Consortium Case Registry--the 2014 Experience.

    Science.gov (United States)

    Rhyee, Sean H; Farrugia, Lynn; Campleman, Sharan L; Wax, Paul M; Brent, Jeffrey

    2015-12-01

    The Toxicology Investigators Consortium (ToxIC) Case Registry was established in 2010 by the American College of Medical Toxicology. The Registry includes all medical toxicology consultations performed at participating sites. The Registry was queried for all cases entered between January 1 and December 31, 2014. Specific data reviewed for analysis included demographics (age, gender, ethnicity), source of consultation, reasons for consultation, agents involved in toxicological exposures, signs, symptoms, clinical findings, fatalities, and treatment. In 2014, 9172 cases were entered in the Registry across 47 active member sites. Females accounted for 51.1 % of cases. The majority (65.1 %) of cases were adults between the ages of 19 and 65. Caucasians made up the largest identified ethnic group (48.9 %). Most Registry cases originated from the inpatient setting (93.5 %), with a large majority of these consultations coming from the emergency department or inpatient admission services. Intentional and unintentional pharmaceutical exposures continued to be the most frequent reasons for consultation, accounting for 61.7 % of cases. Among cases of intentional pharmaceutical exposure, 62.4 % were associated with a self-harm attempt. Non-pharmaceutical exposures accounted for 14.1 % of Registry cases. Similar to the past years, non-opioid analgesics, sedative-hypnotics, and opioids were the most commonly encountered agents. Clinical signs or symptoms were noted in 81.9 % of cases. There were 89 recorded fatalities (0.97 %). Medical treatment (e.g., antidotes, antivenom, chelators, supportive care) was rendered in 62.3 % of cases. Patient demographics and exposure characteristics in 2014 Registry cases remain similar to prior years. The majority of consultations arose in the acute care setting (emergency department or inpatient) and involved exposures to pharmaceutical products. Among exposures, non-opioid analgesics, sedative/hypnotics, and opioids were the most frequently

  20. A newly discovered Bordetella species carries a transcriptionally active CRISPR-Cas with a small Cas9 endonuclease

    Science.gov (United States)

    The Cas9 endonuclease of the Type II-a clustered regularly interspersed short palindromic repeats (CRISPR), of Streptococcus pyogenes (SpCas9) has been adapted as a widely used tool for genome editing and genome engineering. Herein, we describe a gene encoding a novel Cas9 ortholog (BpsuCas9) and th...

  1. Cas9 specifies functional viral targets during CRISPR-Cas adaptation.

    Science.gov (United States)

    Heler, Robert; Samai, Poulami; Modell, Joshua W; Weiner, Catherine; Goldberg, Gregory W; Bikard, David; Marraffini, Luciano A

    2015-03-12

    Clustered regularly interspaced short palindromic repeat (CRISPR) loci and their associated (Cas) proteins provide adaptive immunity against viral infection in prokaryotes. Upon infection, short phage sequences known as spacers integrate between CRISPR repeats and are transcribed into small RNA molecules that guide the Cas9 nuclease to the viral targets (protospacers). Streptococcus pyogenes Cas9 cleavage of the viral genome requires the presence of a 5'-NGG-3' protospacer adjacent motif (PAM) sequence immediately downstream of the viral target. It is not known whether and how viral sequences flanked by the correct PAM are chosen as new spacers. Here we show that Cas9 selects functional spacers by recognizing their PAM during spacer acquisition. The replacement of cas9 with alleles that lack the PAM recognition motif or recognize an NGGNG PAM eliminated or changed PAM specificity during spacer acquisition, respectively. Cas9 associates with other proteins of the acquisition machinery (Cas1, Cas2 and Csn2), presumably to provide PAM-specificity to this process. These results establish a new function for Cas9 in the genesis of prokaryotic immunological memory.

  2. A thermostable Cas9 with increased lifetime in human plasma

    OpenAIRE

    Harrington, LB; Paez-Espino, D; Staahl, BT; Chen, JS; Ma, E; Kyrpides, NC; Doudna, JA

    2017-01-01

    © 2017 The Author(s). CRISPR-Cas9 is a powerful technology that has enabled genome editing in a wide range of species. However, the currently developed Cas9 homologs all originate from mesophilic bacteria, making them susceptible to degradation and unsuitable for applications requiring cleavage at elevated temperatures. Here, we show that the Cas9 protein from the thermophilic bacterium Geobacillus stearothermophilus (GeoCas9) catalyzes RNA-guided DNA cleavage at elevated temperatures. GeoCas...

  3. AKRO/SF: Catch Accounting System (CAS)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Catch Accounting System (CAS) creates total catch estimates for the groundfish fisheries in the Bering Sea/Aleutian Islands and Gulf of Alaska. Each year, quotas...

  4. The new CAS-DIS digital ionosonde

    Directory of Open Access Journals (Sweden)

    Wang Shun

    2013-04-01

    Full Text Available A high quality digital ionosonde called the Chinese Academy of Sciences digital ionosonde (CAS-DIS has been developed for investigations of the ionosphere. Two important features are used for the CAS-DIS; first, the technique of analog down-conversion has been replaced by the new approach of digital down-conversion technology. Secondly, to solve the problem of large instantaneous receiving bandwidth in digital receivers, an analog narrowband tracking filter is used for the CAS-DIS. The center frequency of the filter tracks the carrier frequency transmitted in real-time, to ensure that the frequency components are filtered out of the effective bandwidth. This report describes the system architecture of the CAS-DIS, its main features, and its test results for ionosphere detection. 

  5. The European Cystic Fibrosis Society Patient Registry: valuable lessons learned on how to sustain a disease registry.

    Science.gov (United States)

    Viviani, Laura; Zolin, Anna; Mehta, Anil; Olesen, Hanne Vebert

    2014-06-07

    Disease registries have the invaluable potential to provide an insight into the natural history of the disease under investigation, to provide useful information (e.g. through health indicators) for planning health care services and to identify suitable groups of patients for clinical trials enrolment. However, the establishment and maintenance of disease registries is a burdensome initiative from economical and organisational points of view and experience sharing on registries management is important to avoid waste of resources. The aim of this paper is to discuss the problems embedded in the institution and management of an international disease registry to warn against common mistakes that can derail the best of intentions: we share the experience of the European Cystic Fibrosis Society Patient Registry, which collects data on almost 30,000 patients from 23 countries. We discuss the major problems that researchers often encounter in the creation and management of disease registries: definition of the aims the registry has to reach, definition of the criteria for patients referral to the registry, definition of the information to record, set up of a data quality process, handling of missing data, maintenance of data confidentiality, regulation of data use and dissemination of research results. We give examples on how many crucial aspects were solved by the European Cystic Fibrosis Society Patient Registry regarding objectives, inclusion criteria and variables definition, data management, data quality controls, missing data handling, confidentiality maintenance, data use and results dissemination. We suggest an extensive literature research and discussions in working groups with different stake holders, including patient representatives, on the objectives, inclusion criteria and the information to record. We propose to pilot the recording of few variables and test the applicability of their definition first. The use of a shared electronic platform for data

  6. Phylogeny of Cas9 determines functional exchangeability of dual-RNA and Cas9 among orthologous type II CRISPR-Cas systems

    Science.gov (United States)

    Fonfara, Ines; Le Rhun, Anaïs; Chylinski, Krzysztof; Makarova, Kira S.; Lécrivain, Anne-Laure; Bzdrenga, Janek; Koonin, Eugene V.; Charpentier, Emmanuelle

    2014-01-01

    The CRISPR-Cas-derived RNA-guided Cas9 endonuclease is the key element of an emerging promising technology for genome engineering in a broad range of cells and organisms. The DNA-targeting mechanism of the type II CRISPR-Cas system involves maturation of tracrRNA:crRNA duplex (dual-RNA), which directs Cas9 to cleave invading DNA in a sequence-specific manner, dependent on the presence of a Protospacer Adjacent Motif (PAM) on the target. We show that evolution of dual-RNA and Cas9 in bacteria produced remarkable sequence diversity. We selected eight representatives of phylogenetically defined type II CRISPR-Cas groups to analyze possible coevolution of Cas9 and dual-RNA. We demonstrate that these two components are interchangeable only between closely related type II systems when the PAM sequence is adjusted to the investigated Cas9 protein. Comparison of the taxonomy of bacterial species that harbor type II CRISPR-Cas systems with the Cas9 phylogeny corroborates horizontal transfer of the CRISPR-Cas loci. The reported collection of dual-RNA:Cas9 with associated PAMs expands the possibilities for multiplex genome editing and could provide means to improve the specificity of the RNA-programmable Cas9 tool. PMID:24270795

  7. CIRSE Vascular Closure Device Registry

    NARCIS (Netherlands)

    Reekers, Jim A.; Müller-Hülsbeck, Stefan; Libicher, Martin; Atar, Eli; Trentmann, Jens; Goffette, Pierre; Borggrefe, Jan; Zeleňák, Kamil; Hooijboer, Pieter; Belli, Anna-Maria

    2011-01-01

    Vascular closure devices are routinely used after many vascular interventional radiology procedures. However, there have been no major multicenter studies to assess the safety and effectiveness of the routine use of closure devices in interventional radiology. The CIRSE registry of closure devices

  8. The danish multiple sclerosis registry

    DEFF Research Database (Denmark)

    Brønnum-Hansen, Henrik; Koch-Henriksen, Nils; Stenager, Egon

    2011-01-01

    Introduction: The Danish Multiple Sclerosis (MS) Registry was established in 1956. Content: The register comprises data on all Danes who had MS in 1949 or who have been diagnosed since. Data on new cases and updated information on persons with an MS diagnosis already notified are continuously...

  9. CRISPR-Cas9 Structures and Mechanisms.

    Science.gov (United States)

    Jiang, Fuguo; Doudna, Jennifer A

    2017-05-22

    Many bacterial clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) systems employ the dual RNA-guided DNA endonuclease Cas9 to defend against invading phages and conjugative plasmids by introducing site-specific double-stranded breaks in target DNA. Target recognition strictly requires the presence of a short protospacer adjacent motif (PAM) flanking the target site, and subsequent R-loop formation and strand scission are driven by complementary base pairing between the guide RNA and target DNA, Cas9-DNA interactions, and associated conformational changes. The use of CRISPR-Cas9 as an RNA-programmable DNA targeting and editing platform is simplified by a synthetic single-guide RNA (sgRNA) mimicking the natural dual trans-activating CRISPR RNA (tracrRNA)-CRISPR RNA (crRNA) structure. This review aims to provide an in-depth mechanistic and structural understanding of Cas9-mediated RNA-guided DNA targeting and cleavage. Molecular insights from biochemical and structural studies provide a framework for rational engineering aimed at altering catalytic function, guide RNA specificity, and PAM requirements and reducing off-target activity for the development of Cas9-based therapies against genetic diseases.

  10. CRISPR-Cas: biology, mechanisms and relevance

    Science.gov (United States)

    Hille, Frank

    2016-01-01

    Prokaryotes have evolved several defence mechanisms to protect themselves from viral predators. Clustered regularly interspaced short palindromic repeats (CRISPR) and their associated proteins (Cas) display a prokaryotic adaptive immune system that memorizes previous infections by integrating short sequences of invading genomes—termed spacers—into the CRISPR locus. The spacers interspaced with repeats are expressed as small guide CRISPR RNAs (crRNAs) that are employed by Cas proteins to target invaders sequence-specifically upon a reoccurring infection. The ability of the minimal CRISPR-Cas9 system to target DNA sequences using programmable RNAs has opened new avenues in genome editing in a broad range of cells and organisms with high potential in therapeutical applications. While numerous scientific studies have shed light on the biochemical processes behind CRISPR-Cas systems, several aspects of the immunity steps, however, still lack sufficient understanding. This review summarizes major discoveries in the CRISPR-Cas field, discusses the role of CRISPR-Cas in prokaryotic immunity and other physiological properties, and describes applications of the system as a DNA editing technology and antimicrobial agent. This article is part of the themed issue ‘The new bacteriology’. PMID:27672148

  11. Thyroid Cancer and Tumor Collaborative Registry (TCCR).

    Science.gov (United States)

    Shats, Oleg; Goldner, Whitney; Feng, Jianmin; Sherman, Alexander; Smith, Russell B; Sherman, Simon

    2016-01-01

    A multicenter, web-based Thyroid Cancer and Tumor Collaborative Registry (TCCR, http://tccr.unmc.edu) allows for the collection and management of various data on thyroid cancer (TC) and thyroid nodule (TN) patients. The TCCR is coupled with OpenSpecimen, an open-source biobank management system, to annotate biospecimens obtained from the TCCR subjects. The demographic, lifestyle, physical activity, dietary habits, family history, medical history, and quality of life data are provided and may be entered into the registry by subjects. Information on diagnosis, treatment, and outcome is entered by the clinical personnel. The TCCR uses advanced technical and organizational practices, such as (i) metadata-driven software architecture (design); (ii) modern standards and best practices for data sharing and interoperability (standardization); (iii) Agile methodology (project management); (iv) Software as a Service (SaaS) as a software distribution model (operation); and (v) the confederation principle as a business model (governance). This allowed us to create a secure, reliable, user-friendly, and self-sustainable system for TC and TN data collection and management that is compatible with various end-user devices and easily adaptable to a rapidly changing environment. Currently, the TCCR contains data on 2,261 subjects and data on more than 28,000 biospecimens. Data and biological samples collected by the TCCR are used in developing diagnostic, prevention, treatment, and survivorship strategies against TC.

  12. The Mid-Atlantic Twin Registry, revisited.

    Science.gov (United States)

    Lilley, Emily C H; Silberg, Judy L

    2013-02-01

    The Mid-Atlantic Twin Registry (MATR) is a population-based registry of more than 56,000 twins primarily born or living in Virginia, North Carolina, and South Carolina. The MATR employs several methods of ascertaining twins, and devotes considerable resources to tracking and maintaining communication with MATR participants. Researchers may utilize the MATR for administration of research services including study recruitment, collection of DNA, archival data set creation, as well as data collection through mailed, phone, or online surveys. In addition, the MATR houses the MATR Repository, with over 1,200 blood samples available for researchers interested in DNA genotyping. For over 35 years MATR twins have participated in research studies with investigators from diverse scientific disciplines and various institutions. These studies, which have resulted in numerous publications, have covered a range of topics, including the human microbiome, developmental psychopathology, depression, anxiety, substance use, epigenetics of aging, children of twins, pre-term birth, social attitudes, seizures, eating disorders, as well as sleep homeostasis. Researchers interested in utilizing twins are encouraged to contact the MATR to discuss potential research opportunities.

  13. Agency for Toxic Substances and Disease Registry

    Science.gov (United States)

    ... Z # Search Form Controls Search The CDC submit Agency for Toxic Substances and Disease Registry Note: Javascript ... gov . Recommend on Facebook Tweet Share Compartir The Agency for Toxic Substances and Disease Registry (ATSDR) , based ...

  14. Registries Help Moms Measure Medication Risks

    Science.gov (United States)

    ... in the case of the North American Antiepileptic Drug Pregnancy Registry, which studies the effects of drugs for ... is taking. For example, the North American Antiepileptic Drug Pregnancy Registry website lists more than 30 medications being ...

  15. [Registries for rare diseases : OSSE - An open-source framework for technical implementation].

    Science.gov (United States)

    Storf, Holger; Schaaf, Jannik; Kadioglu, Dennis; Göbel, Jens; Wagner, Thomas O F; Ückert, Frank

    2017-05-01

    Meager amounts of data stored locally, a small number of experts, and a broad spectrum of technological solutions incompatible with each other characterize the landscape of registries for rare diseases in Germany. Hence, the free software Open Source Registry for Rare Diseases (OSSE) was created to unify and streamline the process of establishing specific rare disease patient registries. The data to be collected is specified based on metadata descriptions within the registry framework's so-called metadata repository (MDR), which was developed according to the ISO/IEC 11179 standard. The use of a central MDR allows for sharing the same data elements across any number of registries, thus providing a technical prerequisite for making data comparable and mergeable between registries and promoting interoperability.With OSSE, the foundation is laid to operate linked patient registries while respecting strong data protection regulations. Using the federated search feature, data for clinical studies can be identified across registries. Data integrity, however, remains intact since no actual data leaves the premises without the owner's consent. Additionally, registry solutions other than OSSE can participate via the OSSE bridgehead, which acts as a translator between OSSE registry networks and non-OSSE registries. The pseudonymization service Mainzelliste adds further data protection.Currently, more than 10 installations are under construction in clinical environments (including university hospitals in Frankfurt, Hamburg, Freiburg and Münster). The feedback given by the users will influence further development of OSSE. As an example, the installation process of the registry for undiagnosed patients at University Hospital Frankfurt is described in more detail.

  16. Registries in European post-marketing surveillance

    DEFF Research Database (Denmark)

    Bouvy, Jacoline C; Blake, Kevin; Slattery, Jim

    2017-01-01

    at gaining further insight into the European Medicines Agency's (EMA) requests for new registries and registry studies using existing registries and to review the experience gained in their conduct. METHODS: European Public Assessment Reports were consulted to identify products for which a request...

  17. Quality of trauma care and trauma registries.

    Science.gov (United States)

    Pino Sánchez, F I; Ballesteros Sanz, M A; Cordero Lorenzana, L; Guerrero López, F

    2015-03-01

    Traumatic disease is a major public health concern. Monitoring the quality of services provided is essential for the maintenance and improvement thereof. Assessing and monitoring the quality of care in trauma patient through quality indicators would allow identifying opportunities for improvement whose implementation would improve outcomes in hospital mortality, functional outcomes and quality of life of survivors. Many quality indicators have been used in this condition, although very few ones have a solid level of scientific evidence to recommend their routine use. The information contained in the trauma registries, spread around the world in recent decades, is essential to know the current health care reality, identify opportunities for improvement and contribute to the clinical and epidemiological research. Copyright © 2014 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.

  18. The Canadian Registry for Pulmonary Fibrosis: Design and Rationale of a National Pulmonary Fibrosis Registry

    Directory of Open Access Journals (Sweden)

    Christopher J. Ryerson

    2016-01-01

    Full Text Available Background. The relative rarity and diversity of fibrotic interstitial lung disease (ILD have made it challenging to study these diseases in single-centre cohorts. Here we describe formation of a multicentre Canadian registry that is needed to describe the outcomes of fibrotic ILD and to enable detailed healthcare utilization analyses that will be the cornerstone for future healthcare planning. Methods. The Canadian Registry for Pulmonary Fibrosis (CARE-PF is a prospective cohort anticipated to consist of at least 2,800 patients with fibrotic ILD. CARE-PF will be used to (1 describe the natural history of fibrotic ILD, specifically determining the incidence and outcomes of acute exacerbations of ILD subtypes and (2 determine the impact of ILD and acute exacerbations of ILD on health services use and healthcare costs in the Canadian population. Consecutive patients with fibrotic ILD will be recruited from five Canadian ILD centres over a period of five years. Patients will be followed up as clinically indicated and will complete standardized questionnaires at each clinic visit. Prespecified outcomes and health services use will be measured based on self-report and linkage to provincial health administrative databases. Conclusion. CARE-PF will be among the largest prospective multicentre ILD registries in the world, providing detailed data on the natural history of fibrotic ILD and the healthcare resources used by these patients. As the largest and most comprehensive cohort of Canadian ILD patients, CARE-PF establishes a network for future clinical research and early phase clinical trials and provides a platform for translational and basic science research.

  19. Primary healthcare-based diabetes registry in Puducherry: Design and methods

    Directory of Open Access Journals (Sweden)

    Subitha Lakshminarayanan

    2017-01-01

    Full Text Available Background: Diabetes registries monitor the population prevalence and incidence of diabetes, monitor diabetes control program, provide information of quality of care to health service providers, and provide a sampling frame for interventional studies. This study documents the process of establishing a prospective diabetes registry in a primary health-care setting in Puducherry. Methods: This is a facility-based prospective registry conducted in six randomly selected urban health centers in Puducherry, with enrollment of all known patients with diabetes attending chronic disease clinics. Administrative approvals were obtained from Government Health Services. Manuals for training of medical officers, health-care workers, and case report forms were developed. Diabetes registry was prepared using Epi Info software. Results: In the first phase, demographic characteristics, risk factors, complications, coexisting chronic conditions, lifestyle and medical management, and clinical outcomes were recorded. Around 2177 patients with diabetes have been registered in six Primary Health Centres out of a total of 2948 participants seeking care from chronic disease clinic. Registration coverage ranges from 61% to 105% in these centers. Conclusion: This study has documented methodological details, and learning experiences gained while developing a diabetes registry at the primary health care level and the scope for upscaling to a Management Information System for Diabetes and a State-wide Registry. Improvement in patient care through needs assessment and quality assurance in service delivery is an important theme envisioned by this registry.

  20. [CRISPR/CAS9, the King of Genome Editing Tools].

    Science.gov (United States)

    Bannikov, A V; Lavrov, A V

    2017-01-01

    The discovery of CRISPR/Cas9 brought a hope for having an efficient, reliable, and readily available tool for genome editing. CRISPR/Cas9 is certainly easy to use, while its efficiency and reliability remain the focus of studies. The review describes the general principles of the organization and function of Cas nucleases and a number of important issues to be considered while planning genome editing experiments with CRISPR/Cas9. The issues include evaluation of the efficiency and specificity for Cas9, sgRNA selection, Cas9 variants designed artificially, and use of homologous recombination and nonhomologous end joining in DNA editing.

  1. The Danish Lung Cancer Registry

    DEFF Research Database (Denmark)

    Jakobsen, Erik; Rasmussen, Torben Riis

    2016-01-01

    AIM OF DATABASE: The Danish Lung Cancer Registry (DLCR) was established by the Danish Lung Cancer Group. The primary and first goal of the DLCR was to improve survival and the overall clinical management of Danish lung cancer patients. STUDY POPULATION: All Danish primary lung cancer patients since...... 2000 are included into the registry and the database today contains information on more than 50,000 cases of lung cancer. MAIN VARIABLES: The database contains information on patient characteristics such as age, sex, diagnostic procedures, histology, tumor stage, lung function, performance...... the results are commented for local, regional, and national audits. Indicator results are supported by descriptive reports with details on diagnostics and treatment. CONCLUSION: DLCR has since its creation been used to improve the quality of treatment of lung cancer in Denmark and it is increasingly used...

  2. CIRSE Vascular Closure Device Registry

    International Nuclear Information System (INIS)

    Reekers, Jim A.; Müller-Hülsbeck, Stefan; Libicher, Martin; Atar, Eli; Trentmann, Jens; Goffette, Pierre; Borggrefe, Jan; Zeleňák, Kamil; Hooijboer, Pieter; Belli, Anna-Maria

    2011-01-01

    Purpose: Vascular closure devices are routinely used after many vascular interventional radiology procedures. However, there have been no major multicenter studies to assess the safety and effectiveness of the routine use of closure devices in interventional radiology. Methods: The CIRSE registry of closure devices with an anchor and a plug started in January 2009 and ended in August 2009. A total of 1,107 patients were included in the registry. Results: Deployment success was 97.2%. Deployment failure specified to access type was 8.8% [95% confidence interval (95% CI) 5.0–14.5] for antegrade access and 1.8% (95% CI 1.1–2.9) for retrograde access (P = 0.001). There was no difference in deployment failure related to local PVD at the access site. Calcification was a reason for deployment failure in only 5.9 cm, and two vessel occlusions. Conclusion: The conclusion of this registry of closure devices with an anchor and a plug is that the use of this device in interventional radiology procedures is safe, with a low incidence of serious access site complications. There seems to be no difference in complications between antegrade and retrograde access and other parameters.

  3. CIRSE Vascular Closure Device Registry

    Science.gov (United States)

    Müller-Hülsbeck, Stefan; Libicher, Martin; Atar, Eli; Trentmann, Jens; Goffette, Pierre; Borggrefe, Jan; Zeleňák, Kamil; Hooijboer, Pieter; Belli, Anna-Maria

    2010-01-01

    Purpose Vascular closure devices are routinely used after many vascular interventional radiology procedures. However, there have been no major multicenter studies to assess the safety and effectiveness of the routine use of closure devices in interventional radiology. Methods The CIRSE registry of closure devices with an anchor and a plug started in January 2009 and ended in August 2009. A total of 1,107 patients were included in the registry. Results Deployment success was 97.2%. Deployment failure specified to access type was 8.8% [95% confidence interval (95% CI) 5.0–14.5] for antegrade access and 1.8% (95% CI 1.1–2.9) for retrograde access (P = 0.001). There was no difference in deployment failure related to local PVD at the access site. Calcification was a reason for deployment failure in only 5.9 cm, and two vessel occlusions. Conclusion The conclusion of this registry of closure devices with an anchor and a plug is that the use of this device in interventional radiology procedures is safe, with a low incidence of serious access site complications. There seems to be no difference in complications between antegrade and retrograde access and other parameters. PMID:20981425

  4. A Broad-Spectrum Inhibitor of CRISPR-Cas9.

    Science.gov (United States)

    Harrington, Lucas B; Doxzen, Kevin W; Ma, Enbo; Liu, Jun-Jie; Knott, Gavin J; Edraki, Alireza; Garcia, Bianca; Amrani, Nadia; Chen, Janice S; Cofsky, Joshua C; Kranzusch, Philip J; Sontheimer, Erik J; Davidson, Alan R; Maxwell, Karen L; Doudna, Jennifer A

    2017-09-07

    CRISPR-Cas9 proteins function within bacterial immune systems to target and destroy invasive DNA and have been harnessed as a robust technology for genome editing. Small bacteriophage-encoded anti-CRISPR proteins (Acrs) can inactivate Cas9, providing an efficient off switch for Cas9-based applications. Here, we show that two Acrs, AcrIIC1 and AcrIIC3, inhibit Cas9 by distinct strategies. AcrIIC1 is a broad-spectrum Cas9 inhibitor that prevents DNA cutting by multiple divergent Cas9 orthologs through direct binding to the conserved HNH catalytic domain of Cas9. A crystal structure of an AcrIIC1-Cas9 HNH domain complex shows how AcrIIC1 traps Cas9 in a DNA-bound but catalytically inactive state. By contrast, AcrIIC3 blocks activity of a single Cas9 ortholog and induces Cas9 dimerization while preventing binding to the target DNA. These two orthogonal mechanisms allow for separate control of Cas9 target binding and cleavage and suggest applications to allow DNA binding while preventing DNA cutting by Cas9. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Evolution and classification of the CRISPR-Cas systems

    Science.gov (United States)

    S. Makarova, Kira; H. Haft, Daniel; Barrangou, Rodolphe; J. J. Brouns, Stan; Charpentier, Emmanuelle; Horvath, Philippe; Moineau, Sylvain; J. M. Mojica, Francisco; I. Wolf, Yuri; Yakunin, Alexander F.; van der Oost, John; V. Koonin, Eugene

    2012-01-01

    The CRISPR–Cas (clustered regularly interspaced short palindromic repeats–CRISPR-associated proteins) modules are adaptive immunity systems that are present in many archaea and bacteria. These defence systems are encoded by operons that have an extraordinarily diverse architecture and a high rate of evolution for both the cas genes and the unique spacer content. Here, we provide an updated analysis of the evolutionary relationships between CRISPR–Cas systems and Cas proteins. Three major types of CRISPR–Cas system are delineated, with a further division into several subtypes and a few chimeric variants. Given the complexity of the genomic architectures and the extremely dynamic evolution of the CRISPR–Cas systems, a unified classification of these systems should be based on multiple criteria. Accordingly, we propose a `polythetic' classification that integrates the phylogenies of the most common cas genes, the sequence and organization of the CRISPR repeats and the architecture of the CRISPR–cas loci. PMID:21552286

  6. Engineered CRISPR-Cas9 nucleases with altered PAM specificities.

    Science.gov (United States)

    Kleinstiver, Benjamin P; Prew, Michelle S; Tsai, Shengdar Q; Topkar, Ved V; Nguyen, Nhu T; Zheng, Zongli; Gonzales, Andrew P W; Li, Zhuyun; Peterson, Randall T; Yeh, Jing-Ruey Joanna; Aryee, Martin J; Joung, J Keith

    2015-07-23

    Although CRISPR-Cas9 nucleases are widely used for genome editing, the range of sequences that Cas9 can recognize is constrained by the need for a specific protospacer adjacent motif (PAM). As a result, it can often be difficult to target double-stranded breaks (DSBs) with the precision that is necessary for various genome-editing applications. The ability to engineer Cas9 derivatives with purposefully altered PAM specificities would address this limitation. Here we show that the commonly used Streptococcus pyogenes Cas9 (SpCas9) can be modified to recognize alternative PAM sequences using structural information, bacterial selection-based directed evolution, and combinatorial design. These altered PAM specificity variants enable robust editing of endogenous gene sites in zebrafish and human cells not currently targetable by wild-type SpCas9, and their genome-wide specificities are comparable to wild-type SpCas9 as judged by GUIDE-seq analysis. In addition, we identify and characterize another SpCas9 variant that exhibits improved specificity in human cells, possessing better discrimination against off-target sites with non-canonical NAG and NGA PAMs and/or mismatched spacers. We also find that two smaller-size Cas9 orthologues, Streptococcus thermophilus Cas9 (St1Cas9) and Staphylococcus aureus Cas9 (SaCas9), function efficiently in the bacterial selection systems and in human cells, suggesting that our engineering strategies could be extended to Cas9s from other species. Our findings provide broadly useful SpCas9 variants and, more importantly, establish the feasibility of engineering a wide range of Cas9s with altered and improved PAM specificities.

  7. Versatile Cas9-driven subpopulation selection toolbox for Lactococcus lactis

    NARCIS (Netherlands)

    Els, van der Simon; James, Jennelle K.; Kleerebezem, Michiel; Bron, Peter A.

    2018-01-01

    CRISPR-Cas9 technology has been exploited for the removal or replacement of genetic elements in a wide range of prokaryotes and eukaryotes. Here, we describe the extension of the Cas9 application toolbox to the industrially important dairy species Lactococcus lactis. The Cas9 expression vector

  8. Rational Design of Mini-Cas9 for Transcriptional Activation.

    Science.gov (United States)

    Ma, Dacheng; Peng, Shuguang; Huang, Weiren; Cai, Zhiming; Xie, Zhen

    2018-04-20

    Nuclease dead Cas9 (dCas9) has been widely used for modulating gene expression by fusing with different activation or repression domains. However, delivery of the CRISPR/Cas system fused with various effector domains in a single adeno-associated virus (AAV) remains challenging due to the payload limit. Here, we engineered a set of downsized variants of Cas9 including Staphylococcus aureus Cas9 (SaCas9) that retained DNA binding activity by deleting conserved functional domains. We demonstrated that fusing FokI nuclease domain to the N-terminal of the minimal SaCas9 (mini-SaCas9) or to the middle of the split mini-SaCas9 can trigger efficient DNA cleavage. In addition, we constructed a set of compact transactivation domains based on the tripartite VPR activation domain and self-assembled arrays of split SpyTag:SpyCatch peptides, which are suitable for fusing to the mini-SaCas9. Lastly, we produced a single AAV containing the mini-SaCas9 fused with a downsized transactivation domain along with an optimized gRNA expression cassette, which showed efficient transactivation activity. Our results highlighted a practical approach to generate down-sized CRISPR/Cas9 and gene activation systems for in vivo applications.

  9. The Danish Heart Failure Registry

    DEFF Research Database (Denmark)

    Schjødt, Inge; Nakano, Anne; Egstrup, Kenneth

    2016-01-01

    AIM OF DATABASE: The aim of the Danish Heart Failure Registry (DHFR) is to monitor and improve the care of patients with incident heart failure (HF) in Denmark. STUDY POPULATION: The DHFR includes inpatients and outpatients (≥18 years) with incident HF. Reporting to the DHFR is mandatory......: The main variables recorded in the DHFR are related to the indicators for quality of care in patients with incident HF: performance of echocardiography, functional capacity (New York Heart Association functional classification), pharmacological therapy (angiotensin converting enzyme/angiotensin II...

  10. The Danish National Prescription Registry

    DEFF Research Database (Denmark)

    Kildemoes, Helle Wallach; Toft Sørensen, Henrik; Hallas, Jesper

    2011-01-01

    Introduction: Individual-level data on all prescription drugs sold in Danish community pharmacies has since 1994 been recorded in the Register of Medicinal Products Statistics of the Danish Medicines Agency. Content: The register subset, termed the Danish National Prescription Registry (DNPR......), contains information on dispensed prescriptions, including variables at the level of the drug user, the prescriber, and the pharmacy. Validity and coverage: Reimbursement-driven record keeping, with automated bar-code-based data entry provides data of high quality, including detailed information...

  11. Hernie de Spiegel: a propos d’un cas

    Directory of Open Access Journals (Sweden)

    Karim Ibn Majdoub Hassani

    2010-02-01

    Full Text Available La hernie de Spiegel ou hernie ventrale latérale est une déhiscence inhabituelle apparaissant sur la ligne ou fascia semi-lunaire de Spiegel. C’est une entité clinique rare, représente 0.10 à 1 pourcent des hernies. Aussi, nous a-t-il paru opportun de rapporter ce cas colligé dans le service de chirurgie B du CHU Hassan II de Fès. Nous rapportons l’observation d’une patiente âgée de 60 ans, sans antécédent particulier qui présentais une tuméfaction para ombilicale gauche augmentant progressivement de volume, Une hernie de Spiegel a été suspectée à l’examen clinique, et le diagnostic d’éventration antérolatérale gauche a été retenu à la tomodensitométrie abdominale. Une cure de la hernie par plaque de prolène a été réalisée et les suites opératoires étaient simples. La hernie de Spiegel est une affection rare, son diagnostic clinique peut être difficile. Elle est asymptomatique dans 90 pourcent des cas et Son diagnostic positif est radiologique. Le risque d’étranglement non négligeable impose un traitement chirurgical une fois le diagnostic est confirmé.

  12. Boosting plant immunity with CRISPR/Cas

    OpenAIRE

    Chaparro-Garcia, Angela; Kamoun, Sophien; Nekrasov, Vladimir

    2015-01-01

    CRISPR/Cas has recently been transferred to plants to make them resistant to geminiviruses, a damaging family of DNA viruses. We discuss the potential and the limitations of this method. See related Research: http://www.genomebiology.com/2015/16/1/238

  13. CRISPR-Cas : Adapting to change

    NARCIS (Netherlands)

    Jackson, Simon A.; McKenzie, R.E.; Fagerlund, Robert D.; Kieper, S.N.; Fineran, Peter C.; Brouns, S.J.J.

    2017-01-01

    Bacteria and archaea are engaged in a constant arms race to defend against the ever-present threats of viruses and invasion by mobile genetic elements. The most flexible weapons in the prokaryotic defense arsenal are the CRISPR-Cas adaptive immune systems. These systems are capable of selective

  14. CRISPR-Cas9 gene editing

    NARCIS (Netherlands)

    Oude Blenke, Erik; Evers, Martijn J.W.; Mastrobattista, Enrico; Oost, van der John

    2016-01-01

    The CRISPR-Cas9 gene editing system has taken the biomedical science field by storm, initiating rumors about future Nobel Prizes and heating up a fierce patent war, but also making significant scientific impact. The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), together with

  15. Cas9-triggered chain ablation of cas9 as a gene drive brake

    OpenAIRE

    Wu, Bing; Luo, Liqun; Gao, Xiaojing J.

    2016-01-01

    With the advent of clustered, regularly interspaced, short palindromic repeats (CRISPR)–CRISPR-associated protein 9 (Cas9) technology, researchers can construct gene drives that can bias the inheritance of edited alleles to alter entire populations. As demonstrated with the mutagenic chain reaction in Drosophila4, the CRISPR-Cas9 system can propagate genomic modification together with the genome-editing machinery itself. Although gene drives might have the potential to control insect-borne di...

  16. Cas9 versus Cas12a/Cpf1: Structure-function comparisons and implications for genome editing.

    Science.gov (United States)

    Swarts, Daan C; Jinek, Martin

    2018-05-22

    Cas9 and Cas12a are multidomain CRISPR-associated nucleases that can be programmed with a guide RNA to bind and cleave complementary DNA targets. The guide RNA sequence can be varied, making these effector enzymes versatile tools for genome editing and gene regulation applications. While Cas9 is currently the best-characterized and most widely used nuclease for such purposes, Cas12a (previously named Cpf1) has recently emerged as an alternative for Cas9. Cas9 and Cas12a have distinct evolutionary origins and exhibit different structural architectures, resulting in distinct molecular mechanisms. Here we compare the structural and mechanistic features that distinguish Cas9 and Cas12a, and describe how these features modulate their activity. We discuss implications for genome editing, and how they may influence the choice of Cas9 or Cas12a for specific applications. Finally, we review recent studies in which Cas12a has been utilized as a genome editing tool. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications Regulatory RNAs/RNAi/Riboswitches > Biogenesis of Effector Small RNAs RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes. © 2018 Wiley Periodicals, Inc.

  17. La prise en compte des innovations en matière de mobilité dans la planification urbaine : le cas des Services de transports personnalisés (STP)

    OpenAIRE

    Castex, Élodie; Frère, Séverine; Groux, Annette

    2017-01-01

    Cet article s’intéresse à la façon dont la planification peut ou non permettre aux politiques de déplacements d’innover, de prendre en compte des nouveaux besoins et formes de mobilité. S’appuyant sur un travail de recherche qui porte sur la place des modes de transports alternatifs que sont le covoiturage, l’autopartage, le vélo-en-libre-service et le transport à la demande dans les politiques publiques, cet article tentera de comprendre comment les modes de déplacement innovants sont pris e...

  18. Immunization registries in the EMR Era

    Science.gov (United States)

    Stevens, Lindsay A.; Palma, Jonathan P.; Pandher, Kiran K.; Longhurst, Christopher A.

    2013-01-01

    Background: The CDC established a national objective to create population-based tracking of immunizations through regional and statewide registries nearly 2 decades ago, and these registries have increased coverage rates and reduced duplicate immunizations. With increased adoption of commercial electronic medical records (EMR), some institutions have used unidirectional links to send immunization data to designated registries. However, access to these registries within a vendor EMR has not been previously reported. Purpose: To develop a visually integrated interface between an EMR and a statewide immunization registry at a previously non-reporting hospital, and to assess subsequent changes in provider use and satisfaction. Methods: A group of healthcare providers were surveyed before and after implementation of the new interface. The surveys addressed access of the California Immunization Registry (CAIR), and satisfaction with the availability of immunization information. Information Technology (IT) teams developed a “smart-link” within the electronic patient chart that provides a single-click interface for visual integration of data within the CAIR database. Results: Use of the tool has increased in the months since its initiation, and over 20,000 new immunizations have been exported successfully to CAIR since the hospital began sharing data with the registry. Survey data suggest that providers find this tool improves workflow and overall satisfaction with availability of immunization data. (p=0.009). Conclusions: Visual integration of external registries into a vendor EMR system is feasible and improves provider satisfaction and registry reporting. PMID:23923096

  19. Desserte ferroviaire à grande vitesse, activation des ressources spécifiques et développement du tourisme : le cas de l’agglomération rémoise High speed rail service, specific resources activation, and tourist development: the case of Rheims

    Directory of Open Access Journals (Sweden)

    Sylvie Bazin

    2012-12-01

    Full Text Available La LGV est-européenne a été mise en service le 10 juin 2007. Les acteurs économiques des territoires desservis attendent beaucoup de cette arrivée notamment en matière de développement des tourismes urbain et d’affaires. Mais un tel développement n’est pas automatique. C’est l’appropriation collective de l’innovation que constitue la desserte à grande vitesse dans un territoire qui est au coeur de ses effets positifs. En effet, cette appropriation collective constitue une innovation relationnelle de laquelle peuvent naître des innovations de services complémentaires en matière de tourisme susceptibles de valoriser les ressources spécifiques existantes (patrimoine historique, culturel, gastronomique, etc.. Ainsi, si l’existence de ressources spécifiques joue un rôle pour les villes desservies, les efforts coordonnés des acteurs pour favoriser la “mise en tourisme” de la ville sont également décisifs. L’analyse est illustrée par le cas de l’agglomération rémoise.The East European High-Speed Rail started on June 10, 2007. Economic actors of beneficiary territories are expecting a lot of positive effects such as the development of urban and business tourisms. But such development is not automatic. The collective appropriation of the innovations linked to a High-Speed Rail Service seems to be central for generating positive effects. Indeed, this collective appropriation constitutes a relational innovation, which may give birth to additional services innovations in tourism that could enhance the value of existing specific resources (historical, cultural, gastronomic, etc. and turn them into assets. Thus, if the availability of specific resources plays a specific role for the connected cities, coordinated efforts of actors to promote the tourist development of the city are also decisive. We will illustrate our subject with the case of Rheims.

  20. Support for immunization registries among parents of vaccinated and unvaccinated school-aged children: a case control study

    Directory of Open Access Journals (Sweden)

    Pan William KY

    2006-09-01

    Full Text Available Abstract Background Immunizations have reduced childhood vaccine preventable disease incidence by 98–100%. Continued vaccine preventable disease control depends on high immunization coverage. Immunization registries help ensure high coverage by recording childhood immunizations administered, generating reminders when immunizations are due, calculating immunization coverage and identifying pockets needing immunization services, and improving vaccine safety by reducing over-immunization and providing data for post-licensure vaccine safety studies. Despite substantial resources directed towards registry development in the U.S., only 48% of children were enrolled in a registry in 2004. Parental attitudes likely impact child participation. Consequently, the purpose of this study was to assess the attitudes of parents of vaccinated and unvaccinated school-aged children regarding: support for immunization registries; laws authorizing registries and mandating provider reporting; opt-in versus opt-out registry participation; and financial worth and responsibility of registry development and implementation. Methods A case control study of parents of 815 children exempt from school vaccination requirements and 1630 fully vaccinated children was conducted. Children were recruited from 112 elementary schools in Colorado, Massachusetts, Missouri, and Washington. Surveys administered to the parents, asked about views on registries and perceived utility and safety of vaccines. Parental views were summarized and logistic regression models compared differences between parents of exempt and vaccinated children. Results Surveys were completed by 56.1% of respondents. Fewer than 10% of parents were aware of immunization registries in their communities. Among parents aware of registries, exempt children were more likely to be enrolled (65.0% than vaccinated children (26.5% (p value = 0.01. A substantial proportion of parents of exempt children support immunization

  1. Naturally Occurring Off-Switches for CRISPR-Cas9.

    Science.gov (United States)

    Pawluk, April; Amrani, Nadia; Zhang, Yan; Garcia, Bianca; Hidalgo-Reyes, Yurima; Lee, Jooyoung; Edraki, Alireza; Shah, Megha; Sontheimer, Erik J; Maxwell, Karen L; Davidson, Alan R

    2016-12-15

    CRISPR-Cas9 technology would be enhanced by the ability to inhibit Cas9 function spatially, temporally, or conditionally. Previously, we discovered small proteins encoded by bacteriophages that inhibit the CRISPR-Cas systems of their host bacteria. These "anti-CRISPRs" were specific to type I CRISPR-Cas systems that do not employ the Cas9 protein. We posited that nature would also yield Cas9 inhibitors in response to the evolutionary arms race between bacteriophages and their hosts. Here, we report the discovery of three distinct families of anti-CRISPRs that specifically inhibit the CRISPR-Cas9 system of Neisseria meningitidis. We show that these proteins bind directly to N. meningitidis Cas9 (NmeCas9) and can be used as potent inhibitors of genome editing by this system in human cells. These anti-CRISPR proteins now enable "off-switches" for CRISPR-Cas9 activity and provide a genetically encodable means to inhibit CRISPR-Cas9 genome editing in eukaryotes. VIDEO ABSTRACT. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Unification of Cas protein families and a simple scenario for the origin and evolution of CRISPR-Cas systems

    Directory of Open Access Journals (Sweden)

    Wolf Yuri I

    2011-07-01

    Full Text Available Abstract Background The CRISPR-Cas adaptive immunity systems that are present in most Archaea and many Bacteria function by incorporating fragments of alien genomes into specific genomic loci, transcribing the inserts and using the transcripts as guide RNAs to destroy the genome of the cognate virus or plasmid. This RNA interference-like immune response is mediated by numerous, diverse and rapidly evolving Cas (CRISPR-associated proteins, several of which form the Cascade complex involved in the processing of CRISPR transcripts and cleavage of the target DNA. Comparative analysis of the Cas protein sequences and structures led to the classification of the CRISPR-Cas systems into three Types (I, II and III. Results A detailed comparison of the available sequences and structures of Cas proteins revealed several unnoticed homologous relationships. The Repeat-Associated Mysterious Proteins (RAMPs containing a distinct form of the RNA Recognition Motif (RRM domain, which are major components of the CRISPR-Cas systems, were classified into three large groups, Cas5, Cas6 and Cas7. Each of these groups includes many previously uncharacterized proteins now shown to adopt the RAMP structure. Evidence is presented that large subunits contained in most of the CRISPR-Cas systems could be homologous to Cas10 proteins which contain a polymerase-like Palm domain and are predicted to be enzymatically active in Type III CRISPR-Cas systems but inactivated in Type I systems. These findings, the fact that the CRISPR polymerases, RAMPs and Cas2 all contain core RRM domains, and distinct gene arrangements in the three types of CRISPR-Cas systems together provide for a simple scenario for origin and evolution of the CRISPR-Cas machinery. Under this scenario, the CRISPR-Cas system originated in thermophilic Archaea and subsequently spread horizontally among prokaryotes. Conclusions Because of the extreme diversity of CRISPR-Cas systems, in-depth sequence and structure

  3. CKD.QLD: establishment of a chronic kidney disease [CKD] registry in Queensland, Australia.

    Science.gov (United States)

    Venuthurupalli, Sree K; Hoy, Wendy E; Healy, Helen G; Cameron, Anne; Fassett, Robert G

    2017-06-07

    Chronic kidney disease [CKD] is recognised as a global public health problem. Until recently, the majority of information informing on CKD has been generated from renal registries reporting on patients with end-stage kidney disease [ESKD] and on renal replacement therapy [RRT]. There has been a paucity of information on pre-dialysis CKD cohorts, and many issues related to these poorly described populations are unresolved. To this end, international organizations have called for CKD surveillance systems across all countries. In Australia, we have responded by developing the Chronic Kidney Disease in Queensland [CKD.QLD] with three main platforms consisting of CKD Registry, clinical trials and development of biobank. This registry which is the core component of CKD surveillance was conceptualized specifically for the pre-dialysis population in the public health system in Queensland, Australia. Recruitment started in May 2011, and to date the Registry has evolved as one of the largest CKD cohorts in the world with recruitment close to 7000 patients. The Registry has had many outcomes, including being the nidus for Australia's first National Health and Medical Research Council [NHMRC] CKD Centre of Research Excellence [CKD.CRE]. The Registry, with its linkage to Queensland Health datasets, is reporting, and is expected to continue generating, significant information on multiple aspects of CKD, its trajectory, management and patient outcomes. Intent of the CKD.CRE is to facilitate an expanded Registry network that has representation from health services, both public and private, across Australia.

  4. Use of general practice, diagnostic investigations and hospital services before and after cancer diagnosis - a population-based nationwide registry study of 127,000 incident adult cancer patients

    DEFF Research Database (Denmark)

    Christensen, Karina Garnier; Fenger-Grøn, Morten; Flarup, Kaare Rud

    2012-01-01

    BACKGROUND: Knowledge of patterns in cancer patients' health care utilisation around the time of diagnosis may guide health care resource allocation and provide important insights into this groups' demand for health care services. The health care need of patients with comorbid conditions far...... demand for GP services one year after their diagnosis highlights the importance of close coordination and communication between the primary and the secondary healthcare sector....

  5. The Danish adult diabetes registry

    DEFF Research Database (Denmark)

    Jørgensen, Marit Eika; Kristensen, Jette K.; Husted, Gitte Reventlov

    2016-01-01

    Aim of the database: The aim of the Danish Adult Diabetes Registry (DADR) is to provide data from both the primary health care sector (general practice [GP]) and the secondary sector (specialized outpatient clinics) to assess the quality of treatment given to patients with diabetes. The indicators...... represent process and outcome indicators selected from the literature. Study population: The total diabetes population in Denmark is estimated to be ∼300,000 adult diabetes patients. Approximately 10% have type 1 diabetes, which is managed mainly in the secondary sector, and 90% have type 2 diabetes......, glucose-, blood pressure-, and lipid-lowering treatment (yes/no), insulin pump treatment (yes/ no), and date of last eye and foot examination. Descriptive data: In 2014, the annual report included data regarding over 38,000 patients from outpatient clinics, which is assumed to have included almost all...

  6. The Danish National Chronic Lymphocytic Leukemia Registry

    DEFF Research Database (Denmark)

    da Cunha-Bang, Caspar; Geisler, Christian Hartmann; Enggaard, Lisbeth

    2016-01-01

    AIM: In 2008, the Danish National Chronic Lymphocytic Leukemia Registry was founded within the Danish National Hematology Database. The primary aim of the registry is to assure quality of diagnosis and care of patients with chronic lymphocytic leukemia (CLL) in Denmark. Secondarily, to evaluate...

  7. Windows registry forensics advanced digital forensic analysis of the Windows registry

    CERN Document Server

    Carvey, Harlan

    2011-01-01

    Harlan Carvey brings readers an advanced book on Windows Registry - the most difficult part of Windows to analyze in forensics! Windows Registry Forensics provides the background of the Registry to help develop an understanding of the binary structure of Registry hive files. Approaches to live response and analysis are included, and tools and techniques for postmortem analysis are discussed at length. Tools and techniques will be presented that take the analyst beyond the current use of viewers and into real analysis of data contained in the Registry. This book also has a DVD containing tools, instructions and videos.

  8. Clinical disease registries in acute myocardial infarction.

    Science.gov (United States)

    Ashrafi, Reza; Hussain, Hussain; Brisk, Robert; Boardman, Leanne; Weston, Clive

    2014-06-26

    Disease registries, containing systematic records of cases, have for nearly 100 years been valuable in exploring and understanding various aspects of cardiology. This is particularly true for myocardial infarction, where such registries have provided both epidemiological and clinical information that was not readily available from randomised controlled trials in highly-selected populations. Registries, whether mandated or voluntary, prospective or retrospective in their analysis, have at their core a common study population and common data definitions. In this review we highlight how registries have diversified to offer information on epidemiology, risk modelling, quality assurance/improvement and original research-through data mining, transnational comparisons and the facilitation of enrolment in, and follow-up during registry-based randomised clinical trials.

  9. Les kystes hydatiques du foie rompus dans les voies biliaires: à propos de 120 cas

    Science.gov (United States)

    Moujahid, Mountassir; Tajdine, Mohamed Tarik

    2011-01-01

    Etude rétrospective rapportant une série de kystes hydatiques rompus dans les voies biliaires colligés dans le service de chirurgie de l'hôpital militaire Avicenne à Marrakech. Entre 1990 à 2008, sur 536 kystes hydatiques du foie opérés dans le service, 120 étaient compliqués de rupture dans les voies biliaires soit 22,38%. Il y avait 82hommes et 38 femmes. L’âge moyen était de 35 ans avec des extrêmes allant de 10 à 60 ans. La clinique était dominée par la crise d'angiocholite ou une douleur du flanc droit. L'ictère était isolé dans huit cas. La fistule biliokystique était latente dans plus de 50% des cas. Le traitement a consisté en une résection du dôme saillant dans103cas (85,84%), une périkystectomie chez 11 malades (9,16%) et une lobectomie gauche dans six cas (5%). Le traitement de la fistule bilio kystique a consisté en une suture chez 36malades et un drainage bipolaire dans 25 cas, La déconnexion kysto-biliaire ou cholédocotomie trans hépatico kystique selon Perdomo était pratiquée dans 49cas et une anastomose bilio-digestive cholédoco-duodénale dans 10 cas. La durée moyenne d'hospitalisation était de 20jours. Nous déplorons deux décès par choc septique et un troisième par encéphalopathie secondaire à une cirrhose biliaire. La morbidité était représentée par huit abcès sous phrénique, douze fistules biliaires prolongées et deux occlusions intestinales. Les kystes hydatiques rompus dans les voies biliaires représentent la complication la plus grave de cette pathologie bénigne. Le traitement repose sur des méthodes radicales qui sont d'une efficacité reconnue, mais de réalisation dangereuse et les méthodes conservatrices, en particulier la déconnexion kysto-biliaire qui est une méthode simple et qui donne de bons résultats à court et à long terme. PMID:22384289

  10. CAS Introduction to Accelerator Physics in Bulgaria

    CERN Multimedia

    CERN Bulletin

    2010-01-01

    The CERN Accelerator School (CAS) and the Institute for Nuclear Research & Nuclear Energy (INRNE – Bulgarian Academy of Sciences) jointly organised a course on Introduction to Accelerators, at the Grand Hotel Varna, Bulgaria, from 19 September to 1 October, 2010.   CERN Accelerator School group photo. The course was extremely well attended with 109 participants representing 34 different nationalities, coming from countries as far away as Australia, Canada and Vietnam. The intensive programme comprised 39 lectures, 3 seminars, 4 tutorials where the students were split into three groups, a poster session where students could present their own work, and 7 hours of guided and private study. Feedback from the participants was extremely positive, praising the expertise and enthusiasm of the lecturers, as well as the high standard and excellent quality of their lectures. For the first time at CAS, the CERN Director-General, Rolf Heuer, visited the school and presented a seminar entitled...

  11. CAS - Great success for the DSP course

    CERN Multimedia

    2007-01-01

    The CERN Accelerator School (CAS) and the Uppsala University jointly organized a specialized school on "Digital Signal Processing" in Sigtuna, Sweden from 1-9 June, 2007. This course was a "première" in many ways: firstly the topic had never been addressed by CAS, and secondly the structure of the course differed from the usual specialized courses in the sense that it was composed of 32 hours of theoretical lectures in the mornings and 16 hours "hands-on" courses in the afternoons. The latter, which have been designed by CERN experts, had some logistic implications in transporting computers and circuit boards (DSP and FPGA) to Sweden. The principle of this new approach was extremely well received by the accelerator community and 97 participants representing 23 different nationalities (80% of the participants originating from the CERN Member States) attended the course. As illustrated by the very positive feedback received from th...

  12. Le mal de Pott: à propos de 82 cas

    Directory of Open Access Journals (Sweden)

    Badr Fedoul

    2011-03-01

    Full Text Available Nous rapportant dans cette étude, les résultats de l’expérience du service de neurochirurgie du CHU Hassan II de Fès dans la prise en charge du mal de pott dans la région de Fès. Il s’agit d’une étude rétrospective de quatre-vingt-deux cas; étalée sur une période de cinq ans (janvier 2002 au décembre 2006. L’objectif de ce travail était d’illustrer les différents aspects épidémiologiques, diagnostiques et thérapeutiques de la localisation vertébrale de la tuberculose dans notre pratique. L'âge moyen de nos patients était de 43,1 ans, avec une légère prédominance féminine (53,82%. La durée d'évolution de la maladie était longue (dix mois en moyenne; ceci est expliquée par la symptomatologie initiale insidieuse faite de rachialgies (98,78% et une admission des patients au stade de complications neurologiques (41,46%. La radiographie standard était réalisée chez tous nos patients, et complétée par la TDM dans 86.58% des cas ce qui a permis de déceler la prédominance de l'atteinte dorsale et lombaire. L'IRM est l'examen de choix, elle était demandée chez tous les malades déficitaires (37,8%.Tous nos patients ont bénéficié d'un traitement antibacillaire associé à une immobilisation du foyer pottique. Une décompression par voie antérieure était réalisée chez 29 patients (35,36 %; alors que la laminectomie n'était pratiquée que chez 5 patients (6.09 %, tandis que l'évacuation de l'abcès de psoas était réalisée chez 25 patients (30,48 %. Le diagnostic de certitude histologique était posé dans 51 cas (62,19%. Les meilleurs résultats étaient obtenus chez les malades opérés par voie antérieure, 26 cas (89,65% de récupération totale et 3 cas (10,34% partielle. L'évolution vers la consolidation et la fusion vertébrale était la règle chez tous nos malades et ceci au bout de 4 à 18 mois après le traitement.

  13. Annotation and Classification of CRISPR-Cas Systems.

    Science.gov (United States)

    Makarova, Kira S; Koonin, Eugene V

    2015-01-01

    The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas (CRISPR-associated proteins) is a prokaryotic adaptive immune system that is represented in most archaea and many bacteria. Among the currently known prokaryotic defense systems, the CRISPR-Cas genomic loci show unprecedented complexity and diversity. Classification of CRISPR-Cas variants that would capture their evolutionary relationships to the maximum possible extent is essential for comparative genomic and functional characterization of this theoretically and practically important system of adaptive immunity. To this end, a multipronged approach has been developed that combines phylogenetic analysis of the conserved Cas proteins with comparison of gene repertoires and arrangements in CRISPR-Cas loci. This approach led to the current classification of CRISPR-Cas systems into three distinct types and ten subtypes for each of which signature genes have been identified. Comparative genomic analysis of the CRISPR-Cas systems in new archaeal and bacterial genomes performed over the 3 years elapsed since the development of this classification makes it clear that new types and subtypes of CRISPR-Cas need to be introduced. Moreover, this classification system captures only part of the complexity of CRISPR-Cas organization and evolution, due to the intrinsic modularity and evolutionary mobility of these immunity systems, resulting in numerous recombinant variants. Moreover, most of the cas genes evolve rapidly, complicating the family assignment for many Cas proteins and the use of family profiles for the recognition of CRISPR-Cas subtype signatures. Further progress in the comparative analysis of CRISPR-Cas systems requires integration of the most sensitive sequence comparison tools, protein structure comparison, and refined approaches for comparison of gene neighborhoods.

  14. Annotation and Classification of CRISPR-Cas Systems

    Science.gov (United States)

    Makarova, Kira S.; Koonin, Eugene V.

    2018-01-01

    The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas (CRISPR-associated proteins) is a prokaryotic adaptive immune system that is represented in most archaea and many bacteria. Among the currently known prokaryotic defense systems, the CRISPR-Cas genomic loci show unprecedented complexity and diversity. Classification of CRISPR-Cas variants that would capture their evolutionary relationships to the maximum possible extent is essential for comparative genomic and functional characterization of this theoretically and practically important system of adaptive immunity. To this end, a multipronged approach has been developed that combines phylogenetic analysis of the conserved Cas proteins with comparison of gene repertoires and arrangements in CRISPR-Cas loci. This approach led to the current classification of CRISPR-Cas systems into three distinct types and ten subtypes for each of which signature genes have been identified. Comparative genomic analysis of the CRISPR-Cas systems in new archaeal and bacterial genomes performed over the 3 years elapsed since the development of this classification makes it clear that new types and subtypes of CRISPR-Cas need to be introduced. Moreover, this classification system captures only part of the complexity of CRISPR-Cas organization and evolution, due to the intrinsic modularity and evolutionary mobility of these immunity systems, resulting in numerous recombinant variants. Moreover, most of the cas genes evolve rapidly, complicating the family assignment for many Cas proteins and the use of family profiles for the recognition of CRISPR-Cas subtype signatures. Further progress in the comparative analysis of CRISPR-Cas systems requires integration of the most sensitive sequence comparison tools, protein structure comparison, and refined approaches for comparison of gene neighborhoods. PMID:25981466

  15. EPA Facility Registry System (FRS): NCES

    Science.gov (United States)

    This web feature service contains location and facility identification information from EPA's Facility Registry System (FRS) for the subset of facilities that link to the National Center for Education Statistics (NCES). The primary federal database for collecting and analyzing data related to education in the United States and other Nations, NCES is located in the U.S. Department of Education, within the Institute of Education Sciences. FRS identifies and geospatially locates facilities, sites or places subject to environmental regulations or of environmental interest. Using vigorous verification and data management procedures, FRS integrates facility data from EPA00e2??s national program systems, other federal agencies, and State and tribal master facility records and provides EPA with a centrally managed, single source of comprehensive and authoritative information on facilities. This data set contains the subset of FRS integrated facilities that link to NCES school facilities once the NCES data has been integrated into the FRS database. Additional information on FRS is available at the EPA website http://www.epa.gov/enviro/html/fii/index.html.

  16. La tuberculose sternale: à propos de 2 cas | Ouarssani | Pan African ...

    African Journals Online (AJOL)

    On rapporte deux cas de tuberculose sternale âgés respectivement de 45 ans et de 10ans, colligés au service de pneumologie, l'examen histologique et bactériologique ont permis d'affirmer le diagnostic de tuberculose, et le traitement antibacillaire a permis une évolution favorable .A la lumière de ces observations, les ...

  17. BioShaDock: a community driven bioinformatics shared Docker-based tools registry.

    Science.gov (United States)

    Moreews, François; Sallou, Olivier; Ménager, Hervé; Le Bras, Yvan; Monjeaud, Cyril; Blanchet, Christophe; Collin, Olivier

    2015-01-01

    Linux container technologies, as represented by Docker, provide an alternative to complex and time-consuming installation processes needed for scientific software. The ease of deployment and the process isolation they enable, as well as the reproducibility they permit across environments and versions, are among the qualities that make them interesting candidates for the construction of bioinformatic infrastructures, at any scale from single workstations to high throughput computing architectures. The Docker Hub is a public registry which can be used to distribute bioinformatic software as Docker images. However, its lack of curation and its genericity make it difficult for a bioinformatics user to find the most appropriate images needed. BioShaDock is a bioinformatics-focused Docker registry, which provides a local and fully controlled environment to build and publish bioinformatic software as portable Docker images. It provides a number of improvements over the base Docker registry on authentication and permissions management, that enable its integration in existing bioinformatic infrastructures such as computing platforms. The metadata associated with the registered images are domain-centric, including for instance concepts defined in the EDAM ontology, a shared and structured vocabulary of commonly used terms in bioinformatics. The registry also includes user defined tags to facilitate its discovery, as well as a link to the tool description in the ELIXIR registry if it already exists. If it does not, the BioShaDock registry will synchronize with the registry to create a new description in the Elixir registry, based on the BioShaDock entry metadata. This link will help users get more information on the tool such as its EDAM operations, input and output types. This allows integration with the ELIXIR Tools and Data Services Registry, thus providing the appropriate visibility of such images to the bioinformatics community.

  18. Services

    International Nuclear Information System (INIS)

    Hardeman, F.

    1998-01-01

    The objectives of the services section is (1) to offer complete services in health-physics measurements according to international quality standards, (2) to improve continuously these measurement techniques and to follow up international recommendations and legislation concerning the surveillance of workers, (3) to support and advise nuclear and non-nuclear industry on problems of radioactive contamination. Achievements related to gamma spectrometry, whole-body counting, beta and alpha spectrometry, dosimetry, radon measurements, calibration, instrumentation, and neutron activation analysis are described

  19. Linkage between the Danish National Health Service Prescription Database, the Danish Fetal Medicine Database, and other Danish registries as a tool for the study of drug safety in pregnancy

    DEFF Research Database (Denmark)

    Pedersen, Lars Henning; Petersen, Olav Bjørn; Nørgaard, Mette

    2016-01-01

    A linked population-based database is being created in Denmark for research on drug safety during pregnancy. It combines information from the Danish National Health Service Prescription Database (with information on all prescriptions reimbursed in Denmark since 2004), the Danish Fetal Medicine...

  20. Cas4 Facilitates PAM-Compatible Spacer Selection during CRISPR Adaptation

    OpenAIRE

    Sebastian N. Kieper; Cristóbal Almendros; Juliane Behler; Rebecca E. McKenzie; Franklin L. Nobrega; Anna C. Haagsma; Jochem N.A. Vink; Wolfgang R. Hess; Stan J.J. Brouns

    2018-01-01

    Summary: CRISPR-Cas systems adapt their immunological memory against their invaders by integrating short DNA fragments into clustered regularly interspaced short palindromic repeat (CRISPR) loci. While Cas1 and Cas2 make up the core machinery of the CRISPR integration process, various class I and II CRISPR-Cas systems encode Cas4 proteins for which the role is unknown. Here, we introduced the CRISPR adaptation genes cas1, cas2, and cas4 from the type I-D CRISPR-Cas system of Synechocystis sp....

  1. CRISPR-Cas9 Based Engineering of Actinomycetal Genomes

    DEFF Research Database (Denmark)

    Tong, Yaojun; Charusanti, Pep; Zhang, Lixin

    2015-01-01

    . To facilitate the genetic manipulation of actinomycetes, we developed a highly efficient CRISPR-Cas9 system to delete gene(s) or gene cluster(s), implement precise gene replacements, and reversibly control gene expression in actinomycetes. We demonstrate our system by targeting two genes, actIORF1 (SCO5087......) and actVB (SCO5092), from the actinorhodin biosynthetic gene cluster in Streptomyces coelicolor A3(2). Our CRISPR-Cas9 system successfully inactivated the targeted genes. When no templates for homology-directed repair (HDR) were present, the site-specific DNA double-strand breaks (DSBs) introduced by Cas9....... Moreover, we developed a system to efficiently and reversibly control expression of target genes, deemed CRISPRi, based on a catalytically dead variant of Cas9 (dCas9). The CRISPR-Cas9 based system described here comprises a powerful and broadly applicable set of tools to manipulate actinomycetal genomes....

  2. The Western Denmark Cardiac Computed Tomography Registry

    DEFF Research Database (Denmark)

    Nielsen, Lene Hüche; Nørgaard, Bjarne Linde; Tilsted, Hans-Henrik

    2014-01-01

    BACKGROUND: As a subregistry to the Western Denmark Heart Registry (WDHR), the Western Denmark Cardiac Computed Tomography Registry (WDHR-CCTR) is a clinical database established in 2008 to monitor and improve the quality of cardiac computed tomography (CT) in Western Denmark. OBJECTIVE: We...... examined the content, data quality, and research potential of the WDHR-CCTR. METHODS: We retrieved 2008-2012 data to examine the 1) content; 2) completeness of procedure registration using the Danish National Patient Registry as reference; 3) completeness of variable registration comparing observed vs...

  3. Disabling Cas9 by an anti-CRISPR DNA mimic.

    Science.gov (United States)

    Shin, Jiyung; Jiang, Fuguo; Liu, Jun-Jie; Bray, Nicolas L; Rauch, Benjamin J; Baik, Seung Hyun; Nogales, Eva; Bondy-Denomy, Joseph; Corn, Jacob E; Doudna, Jennifer A

    2017-07-01

    CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 gene editing technology is derived from a microbial adaptive immune system, where bacteriophages are often the intended target. Natural inhibitors of CRISPR-Cas9 enable phages to evade immunity and show promise in controlling Cas9-mediated gene editing in human cells. However, the mechanism of CRISPR-Cas9 inhibition is not known, and the potential applications for Cas9 inhibitor proteins in mammalian cells have not been fully established. We show that the anti-CRISPR protein AcrIIA4 binds only to assembled Cas9-single-guide RNA (sgRNA) complexes and not to Cas9 protein alone. A 3.9 Å resolution cryo-electron microscopy structure of the Cas9-sgRNA-AcrIIA4 complex revealed that the surface of AcrIIA4 is highly acidic and binds with a 1:1 stoichiometry to a region of Cas9 that normally engages the DNA protospacer adjacent motif. Consistent with this binding mode, order-of-addition experiments showed that AcrIIA4 interferes with DNA recognition but has no effect on preformed Cas9-sgRNA-DNA complexes. Timed delivery of AcrIIA4 into human cells as either protein or expression plasmid allows on-target Cas9-mediated gene editing while reducing off-target edits. These results provide a mechanistic understanding of AcrIIA4 function and demonstrate that inhibitors can modulate the extent and outcomes of Cas9-mediated gene editing.

  4. Department of Defense Birth and Infant Health Registry: Select Reproductive Health Outcomes, 2003-2014 (Open Access Publisher’s Version)

    Science.gov (United States)

    2017-11-01

    along with prior Registry analyses, pro- vide reassurance that military service is not independently associated with increased risks for select...deliveries are included in the Registry’s infant population due to standard exclusions . November 2017 Vol. 24 No. 11 MSMR Page 49 leveraging Registry data...exposure and adverse event detection in the Military Health System. Pharmacoepidemiol Drug Saf. 2015;24(5):510–517. 13. MacDorman MF, Gregory EC. Fetal

  5. Control of gene expression by CRISPR-Cas systems

    Science.gov (United States)

    2013-01-01

    Clustered regularly interspaced short palindromic repeats (CRISPR) loci and their associated cas (CRISPR-associated) genes provide adaptive immunity against viruses (phages) and other mobile genetic elements in bacteria and archaea. While most of the early work has largely been dominated by examples of CRISPR-Cas systems directing the cleavage of phage or plasmid DNA, recent studies have revealed a more complex landscape where CRISPR-Cas loci might be involved in gene regulation. In this review, we summarize the role of these loci in the regulation of gene expression as well as the recent development of synthetic gene regulation using engineered CRISPR-Cas systems. PMID:24273648

  6. La tuberculose extra-ganglionnaire primitive de la sphère ORL: à propos de 15 cas

    Science.gov (United States)

    Touati, Mohamed Mliha; Darouassi, Youssef; Chihani, Mehdi; Lakouichmi, Mohammed; Tourabi, Khalid; Ammar, Haddou; Bouaity, Brahim

    2014-01-01

    Les localisations ORL extra ganglionnaires de la tuberculose sont rares. La symptomatologie clinique ainsi que les examens paracliniques sont souvent trompeurs,posant ainsi le problème de diagnostic différentiel avec la pathologie tumorale. Nous rapportons 15 cas de localisations extra ganglionnaires de tuberculose, colligés au service ORL et CCF de l'Hopital Militaire Avicenne de Marrakech colligés entre 2009 et 2013. L’âge moyen de nos patients est de 33 ans. L’étude topographique a montré 6 cas au niveau du cavum, un cas de miliaire tuberculeuse pharyngée, 4 cas laryngés; 2 localisations auriculaires; 1 parotidienne et 1 localisation sous maxillaire. Le diagnostic était anatomopathologiquedans tous les cas. Tous nos patients ont reçu un traitement antituberculeux avec une bonne évolution. Mots-clés: Tuberculose, amygdale, rhinopharynx, larynx, glandes salivaires,Oreille moyenne. PMID:25815100

  7. Veterans Affairs Central Cancer Registry (VACCR)

    Data.gov (United States)

    Department of Veterans Affairs — The Veterans Affairs Central Cancer Registry (VACCR) receives and stores information on cancer diagnosis and treatment constraints compiled and sent in by the local...

  8. Occupational dose assessment and national dose registry system in Iran

    International Nuclear Information System (INIS)

    Jafari-Zadeh, M.; Nazeri, F.; Hosseini-Pooya, S. M.; Taheri, M.; Gheshlaghi, F.; Kardan, M. R.; Babakhani, A.; Rastkhah, N.; Yousefi-Nejad, F.; Darabi, M.; Oruji, T.; Gholamali-Zadeh, Z.; Karimi-Diba, J.; Kazemi-Movahed, A. A.; Dashti-Pour, M. R.; Enferadi, A.; Jahanbakhshian, M. H.; Sadegh-Khani, M. R.

    2011-01-01

    This report presents status of external and internal dose assessment of workers and introducing the structure of National Dose Registry System of Iran (NDRSI). As well as types of individual dosemeters in use, techniques for internal dose assessment are presented. Results obtained from the International Atomic Energy Agency intercomparison programme on measurement of personal dose equivalent H p (10) and consistency of the measured doses with the delivered doses are shown. Also, implementation of dosimetry standards, establishment of quality management system, authorisation and approval procedure of dosimetry service providers are discussed. (authors)

  9. Toxic substances registry system: Index of material safety data sheets

    Science.gov (United States)

    1993-01-01

    The Material Safety Data Sheets (MSDS's) listed in this index reflect product inventories and associated MSDS's which were submitted to the Toxic Substances Registry database maintained by the Base Operations Contractor at the Kennedy Space Center. The purpose of this index is to provide KSC government, contractor, and tenant organizations a means to access information on the hazards associated with these chemicals. The Toxic Substance Registry Service (TSRS) was established to manage information dealing with the storage and use of toxic and otherwise hazardous materials at KSC. As a part of this service, the BOC Environmental Health Services maintains a central repository of MSDS's which were provided to TSRS. The data on the TSRS are obtained from NASA, contractor, and tenant organizations who use or store hazardous materials at KSC. It is the responsibility of these organizations to conduct inventories, obtain MSDS's, distribute Hazard Communication information to their employees, and otherwise implement compliance with appropriate Federal, State, and NASA Hazard Communication and Worker Right-to-Know regulations and policies.

  10. Definition, epidemiology and registries of pulmonary hypertension.

    Science.gov (United States)

    Awdish, R; Cajigas, H

    2016-05-01

    Pulmonary arterial hypertension (PAH) is a subcategory of pulmonary hypertension (PH) that comprises a group of disorders with similar pulmonary vascular pathology. Though PH is common, the estimated incidence of IPAH is 1-3 cases per million, making it a rare disease. The hemodynamic definition of PAH is a mean pulmonary artery pressure at rest >OR = 25 mm Hg in the presence of a pulmonary capillary wedge pressure registries. These registries have been indispensable in the characterization and mapping of the natural history of the disease. Equations and risk calculators derived from registries have given clinicians a basis for risk stratification and prognostication. The sequential accumulation of data since the registries began in the 1980s allows for comparisons to be made. Patients who are differentiated by treatment eras and environments can be contrasted. Variability among inclusion criteria similarly allows for comparisons of these subpopulations. This article provides an overview of available registries, highlights insights provided by each and discusses key issues around the interpretation and extrapolation of data from PAH registries. Registries have allowed us to appreciate the improvement in survival afforded by modern therapy and enhanced detection of this disease. Moving forward, a more global approach to registries is needed, as is enhanced collaboration and centralization.

  11. Occupational Disease Registries-Characteristics and Experiences.

    Science.gov (United States)

    Davoodi, Somayeh; Haghighi, Khosro Sadeghniat; Kalhori, Sharareh Rostam Niakan; Hosseini, Narges Shams; Mohammadzadeh, Zeinab; Safdari, Reza

    2017-06-01

    Due to growth of occupational diseases and also increase of public awareness about their consequences, attention to various aspects of diseases and improve occupational health and safety has found great importance. Therefore, there is the need for appropriate information management tools such as registries in order to recognitions of diseases patterns and then making decision about prevention, early detection and treatment of them. These registries have different characteristics in various countries according to their occupational health priorities. Aim of this study is evaluate dimensions of occupational diseases registries including objectives, data sources, responsible institutions, minimum data set, classification systems and process of registration in different countries. In this study, the papers were searched using the MEDLINE (PubMed) Google scholar, Scopus, ProQuest and Google. The search was done based on keyword in English for all motor engines including "occupational disease", "work related disease", "surveillance", "reporting", "registration system" and "registry" combined with name of the countries including all subheadings. After categorizing search findings in tables, results were compared with each other. Important aspects of the registries studied in ten countries including Finland, France, United Kingdom, Australia, Czech Republic, Malaysia, United States, Singapore, Russia and Turkey. The results show that surveyed countries have statistical, treatment and prevention objectives. Data sources in almost the rest of registries were physicians and employers. The minimum data sets in most of them consist of information about patient, disease, occupation and employer. Some of countries have special occupational related classification systems for themselves and some of them apply international classification systems such as ICD-10. Finally, the process of registration system was different in countries. Because occupational diseases are often

  12. Workload and time management in central cancer registries: baseline data and implication for registry staffing.

    Science.gov (United States)

    Chapman, Susan A; Mulvihill, Linda; Herrera, Carolina

    2012-01-01

    The Workload and Time Management Survey of Central Cancer Registries was conducted in 2011 to assess the amount of time spent on work activities usually performed by cancer registrars. A survey including 39 multi-item questions,together with a work activities data collection log, was sent by email to the central cancer registry (CCR) manager in each of the 50 states and the District of Columbia. Twenty-four central cancer registries (47%) responded to the survey.Results indicate that registries faced reductions in budgeted staffing from 2008-2009. The number of source records and total cases were important indicators of workload. Four core activities, including abstracting at the registry, visual editing,case consolidation, and resolving edit reports, accounted for about half of registry workload. We estimate an average of 12.4 full-time equivalents (FTEs) are required to perform all cancer registration activities tracked by the survey; however,estimates vary widely by registry size. These findings may be useful for registries as a benchmark for their own registry workload and time-management data and to develop staffing guidelines.

  13. Quality Registries in Sweden, Healthcare Improvements and Elderly Persons with Cognitive Impairments.

    Science.gov (United States)

    Mattsson, Titti

    2016-12-01

    Policy-makers, the medical industry and researchers are demonstrating a keen interest in the potential of large registries of patient data, both nationally and internationally. The registries offer promising ways to measure and develop operational quality within health and medical care services. As a result of certain favourable patient data regulations and government funding, the development of quality registries is advanced in Sweden. The combination of increasing demand for more cost-efficient healthcare that can accommodate the demographic development of a rapidly ageing population, and the emergence of eHealth with an increasing digitalisation of patient data, calls attention to quality registries as a possible way for healthcare improvements. However, even if the use of registries has many advantages, there are some drawbacks from a patient privacy point of view. This article aims to analyse this growing interdependence of quality registries for the healthcare sector. It discusses some lessons from the Swedish case, with particular focus on the collection of data from elderly persons with cognitive impairments.

  14. Oral cancer in Libya and development of regional oral cancer registries: A review.

    Science.gov (United States)

    BenNasir, E; El Mistiri, M; McGowan, R; Katz, R V

    2015-10-01

    The aims of this paper are three-fold: (1) to summarize the current epidemiological data on oral cancer in Libya as reported in the published literature and as compared to other national oral cancer rates in the region; (2) to present both the history of the early development, and future goals, of population-based oral cancer tumor registries in Libya as they partner with the more established regional and international population-based cancer tumor registries; and, (3) to offer recommendations that will likely be required in the near future if these nascent, population-based Libyan oral cancer registries are to establish themselves as on-going registries for describing the oral cancer disease patterns and risk factors in Libya as well as for prevention and treatment. This comprehensive literature review revealed that the current baseline incidence of oral cancer in Libya is similar to those of other North Africa countries and China, but is relatively low compared to the United Kingdom, the United States, and India. The recently established Libyan National Cancer Registry Program, initiated in 2007, while envisioning five cooperating regional cancer registries, continues to operate at a relatively suboptimal level. Lack of adequate levels of national funding continue to plague its development…and the accompanying quality of service that could be provided to the Libyan people.

  15. CAS - CERN Accelerator School: Power Converters

    CERN Document Server

    2015-01-01

    These proceedings collate lectures given at the twenty-eighth specialized course organised by the CERN Accelerator School (CAS). The course was held at the Hotel du Parc, Baden, Switzerland from 7 - 14 May 2014, in collaboration with the Paul Scherrer Institute. Following introductory lectures on accelerators and the requirements on power converters, the course covered components and topologies of the different types of power converters needed for particle accelerators. Issues of design, control and exploitation in a sometimes-hostile environment were addressed. Site visits to ABB and PSI provided an insight into state-of-the-art power converter production and operation, while topical seminars completed the programme.

  16. Recent Advances in Genome Editing Using CRISPR/Cas9

    Science.gov (United States)

    Ding, Yuduan; Li, Hong; Chen, Ling-Ling; Xie, Kabin

    2016-01-01

    The CRISPR (clustered regularly interspaced short palindromic repeat)-Cas9 (CRISPR-associated nuclease 9) system is a versatile tool for genome engineering that uses a guide RNA (gRNA) to target Cas9 to a specific sequence. This simple RNA-guided genome-editing technology has become a revolutionary tool in biology and has many innovative applications in different fields. In this review, we briefly introduce the Cas9-mediated genome-editing method, summarize the recent advances in CRISPR/Cas9 technology, and discuss their implications for plant research. To date, targeted gene knockout using the Cas9/gRNA system has been established in many plant species, and the targeting efficiency and capacity of Cas9 has been improved by optimizing its expression and that of its gRNA. The CRISPR/Cas9 system can also be used for sequence-specific mutagenesis/integration and transcriptional control of target genes. We also discuss off-target effects and the constraint that the protospacer-adjacent motif (PAM) puts on CRISPR/Cas9 genome engineering. To address these problems, a number of bioinformatic tools are available to help design specific gRNAs, and new Cas9 variants and orthologs with high fidelity and alternative PAM specificities have been engineered. Owing to these recent efforts, the CRISPR/Cas9 system is becoming a revolutionary and flexible tool for genome engineering. Adoption of the CRISPR/Cas9 technology in plant research would enable the investigation of plant biology at an unprecedented depth and create innovative applications in precise crop breeding. PMID:27252719

  17. New CRISPR-Cas systems from uncultivated microbes

    Science.gov (United States)

    Burstein, David; Harrington, Lucas B.; Strutt, Steven C.; Probst, Alexander J.; Anantharaman, Karthik; Thomas, Brian C.; Doudna, Jennifer A.; Banfield, Jillian F.

    2017-02-01

    CRISPR-Cas systems provide microbes with adaptive immunity by employing short DNA sequences, termed spacers, that guide Cas proteins to cleave foreign DNA. Class 2 CRISPR-Cas systems are streamlined versions, in which a single RNA-bound Cas protein recognizes and cleaves target sequences. The programmable nature of these minimal systems has enabled researchers to repurpose them into a versatile technology that is broadly revolutionizing biological and clinical research. However, current CRISPR-Cas technologies are based solely on systems from isolated bacteria, leaving the vast majority of enzymes from organisms that have not been cultured untapped. Metagenomics, the sequencing of DNA extracted directly from natural microbial communities, provides access to the genetic material of a huge array of uncultivated organisms. Here, using genome-resolved metagenomics, we identify a number of CRISPR-Cas systems, including the first reported Cas9 in the archaeal domain of life, to our knowledge. This divergent Cas9 protein was found in little-studied nanoarchaea as part of an active CRISPR-Cas system. In bacteria, we discovered two previously unknown systems, CRISPR-CasX and CRISPR-CasY, which are among the most compact systems yet discovered. Notably, all required functional components were identified by metagenomics, enabling validation of robust in vivo RNA-guided DNA interference activity in Escherichia coli. Interrogation of environmental microbial communities combined with in vivo experiments allows us to access an unprecedented diversity of genomes, the content of which will expand the repertoire of microbe-based biotechnologies.

  18. Review of U.S. registries for psoriasis.

    Science.gov (United States)

    Amin, Mina; No, Daniel J; Wu, Jashin J

    2017-12-01

    Patient registries are databases comprised of standardized clinical data for a specific population of patients with a particular disease or medical condition. Information from patient registries allows clinicians to assess long-lasting outcomes in patients with a specific disease, such as psoriasis. Our primary objective was to identify available psoriasis registries in the United States (U.S.) and evaluate the application of patient registries compared to clinical trials. We searched Google, the Registry of Patient Registries, Orphanet and ClinicalTrials.gov to create a list of U.S. psoriasis registries. We also performed a literature review on the application of psoriasis registries using PubMed. We identified 6 psoriasis patient registries in the United States. Patient registries are frequently used for psoriasis in the U.S. and provide important information about the safety, efficacy and long-term effects of systemic therapies.

  19. Highly specific targeted mutagenesis in plants using Staphylococcus aureus Cas9

    OpenAIRE

    Hidetaka Kaya; Masafumi Mikami; Akira Endo; Masaki Endo; Seiichi Toki

    2016-01-01

    The CRISPR/Cas9 system is an efficient and convenient tool for genome editing in plants. Cas9 nuclease derived from Streptococcus pyogenes (Sp) is commonly used in this system. Recently, Staphylococcus aureus Cas9 (SaCas9)-mediated genome editing was reported in human cells and Arabidopsis. Because SaCas9 (1053 a.a.) is smaller than SpCas9 (1368 a.a.), SaCas9 could have substantial advantages for delivering and expressing Cas9 protein, especially using virus vectors. Since the protospacer adj...

  20. A newly discovered Bordetella species carries a transcriptionally active CRISPR-Cas with a small Cas9 endonuclease.

    Science.gov (United States)

    Ivanov, Yury V; Shariat, Nikki; Register, Karen B; Linz, Bodo; Rivera, Israel; Hu, Kai; Dudley, Edward G; Harvill, Eric T

    2015-10-26

    Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated genes (cas) are widely distributed among bacteria. These systems provide adaptive immunity against mobile genetic elements specified by the spacer sequences stored within the CRISPR. The CRISPR-Cas system has been identified using Basic Local Alignment Search Tool (BLAST) against other sequenced and annotated genomes and confirmed via CRISPRfinder program. Using Polymerase Chain Reactions (PCR) and Sanger DNA sequencing, we discovered CRISPRs in additional bacterial isolates of the same species of Bordetella. Transcriptional activity and processing of the CRISPR have been assessed via RT-PCR. Here we describe a novel Type II-C CRISPR and its associated genes-cas1, cas2, and cas9-in several isolates of a newly discovered Bordetella species. The CRISPR-cas locus, which is absent in all other Bordetella species, has a significantly lower GC-content than the genome-wide average, suggesting acquisition of this locus via horizontal gene transfer from a currently unknown source. The CRISPR array is transcribed and processed into mature CRISPR RNAs (crRNA), some of which have homology to prophages found in closely related species B. hinzii. Expression of the CRISPR-Cas system and processing of crRNAs with perfect homology to prophages present in closely related species, but absent in that containing this CRISPR-Cas system, suggest it provides protection against phage predation. The 3,117-bp cas9 endonuclease gene from this novel CRISPR-Cas system is 990 bp smaller than that of Streptococcus pyogenes, the 4,017-bp allele currently used for genome editing, and which may make it a useful tool in various CRISPR-Cas technologies.

  1. Production of Purified CasRNPs for Efficacious Genome Editing.

    Science.gov (United States)

    Lingeman, Emily; Jeans, Chris; Corn, Jacob E

    2017-10-02

    CRISPR-Cas systems have been harnessed as modular genome editing reagents for functional genomics and show promise to cure genetic diseases. Directed by a guide RNA, a Cas effector introduces a double stranded break in DNA and host cell DNA repair leads to the introduction of errors (e.g., to knockout a gene) or a programmed change. Introduction of a Cas effector and guide RNA as a purified Cas ribonucleoprotein complex (CasRNP) has recently emerged as a powerful approach to alter cell types and organisms. Not only does CasRNP editing exhibit increased efficacy and specificity, it avoids optimization and iteration of species-specific factors such as codon usage, promoters, and terminators. CasRNP editing has been rapidly adopted for research use in many contexts and is quickly becoming a popular method to edit primary cells for therapeutic application. This article describes how to make a Cas9 RNP and outlines its use for gene editing in human cells. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

  2. Engineering the Caenorhabditis elegans genome with CRISPR/Cas9

    NARCIS (Netherlands)

    Waaijers, Selma; Boxem, Mike

    2014-01-01

    The development in early 2013 of CRISPR/Cas9-based genome engineering promises to dramatically advance our ability to alter the genomes of model systems at will. A single, easily produced targeting RNA guides the Cas9 endonuclease to a specific DNA sequence where it creates a double strand break.

  3. CATO--A Guided User Interface for Different CAS

    Science.gov (United States)

    Janetzko, Hans-Dieter

    2017-01-01

    CATO is a new user interface, written in Java and developed by the author as a response to the significant difficulties faced by students who only sporadically use computer algebra systems (CAS). The usage of CAS in mathematical lectures should be an integral part of mathematical instruction. However, difficulties arise for those students who have…

  4. From Calculus to Dynamical Systems through DGS and CAS

    Science.gov (United States)

    García, Jeanett López; Zamudio, Jorge Javier Jiménez

    2015-01-01

    Several factors have motivated the use of CAS or DGS in the teaching-learning process, such as: the development of new technologies, the availability of computers, and the widespread use of the Internet, among others. Even more, the trend to include CAS and DGS in the curricula of some undergraduate studies has resulted in the instruction of the…

  5. NSP-CAS Protein Complexes: Emerging Signaling Modules in Cancer.

    Science.gov (United States)

    Wallez, Yann; Mace, Peter D; Pasquale, Elena B; Riedl, Stefan J

    2012-05-01

    The CAS (CRK-associated substrate) family of adaptor proteins comprises 4 members, which share a conserved modular domain structure that enables multiple protein-protein interactions, leading to the assembly of intracellular signaling platforms. Besides their physiological role in signal transduction downstream of a variety of cell surface receptors, CAS proteins are also critical for oncogenic transformation and cancer cell malignancy through associations with a variety of regulatory proteins and downstream effectors. Among the regulatory partners, the 3 recently identified adaptor proteins constituting the NSP (novel SH2-containing protein) family avidly bind to the conserved carboxy-terminal focal adhesion-targeting (FAT) domain of CAS proteins. NSP proteins use an anomalous nucleotide exchange factor domain that lacks catalytic activity to form NSP-CAS signaling modules. Additionally, the NSP SH2 domain can link NSP-CAS signaling assemblies to tyrosine-phosphorylated cell surface receptors. NSP proteins can potentiate CAS function by affecting key CAS attributes such as expression levels, phosphorylation state, and subcellular localization, leading to effects on cell adhesion, migration, and invasion as well as cell growth. The consequences of these activities are well exemplified by the role that members of both families play in promoting breast cancer cell invasiveness and resistance to antiestrogens. In this review, we discuss the intriguing interplay between the NSP and CAS families, with a particular focus on cancer signaling networks.

  6. Teaching Undergraduate Mathematics Using CAS Technology: Issues and Prospects

    Science.gov (United States)

    Tobin, Patrick C.; Weiss, Vida

    2016-01-01

    The use of handheld CAS technology in undergraduate mathematics courses in Australia is paradoxically shrinking under sustained disapproval or disdain from the professional mathematics community. Mathematics education specialists argue with their mathematics colleagues over a range of issues in course development and this use of CAS or even…

  7. CRISPR/Cas13 as a Tool for RNA Interference

    KAUST Repository

    Ali, Zahir

    2018-03-28

    Almost all biological processes involve RNA, making it crucial to develop tools for manipulation of the transcriptome. The bacterial CRISPR/Cas13 system was recently rewired to facilitate RNA manipulation in eukaryotes, including plants. We discuss here the opportunities and limitations of using CRISPR/Cas13 in plants for various types of RNA manipulation.

  8. Progress Scored in Management Information System at CAS

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ CAS initiative to upgrade its management information system (MIS) is making significant progress. Recently, 116 CAS subordinates have completed their online trial operation of a MIS project at the Academy, called Academia Resource Planning (ARP), marking an important phased achievement of the initiative.

  9. Class 2 CRISPR-Cas RNA-guided endonucleases

    DEFF Research Database (Denmark)

    Stella, Stefano; Alcón, Pablo; Montoya, Guillermo

    2017-01-01

    CRISPR-Cas is a bacterial defense system against phage infection and nucleic acid invasion. Class 2 type II CRISPR-Cas9 has also been widely used for genome engineering. Here, we review novel insights into the CRISPR class 2 type V enzymes, specifically Cpf1 and C2c1, which display different DNA-...

  10. CRISPR/Cas9 based genome editing of Penicillium chrysogenum

    NARCIS (Netherlands)

    Pohl, Carsten; Kiel, Jan A K W; Driessen, Arnold J M; Bovenberg, Roel A L; Nygård, Yvonne

    2016-01-01

    CRISPR/Cas9 based systems have emerged as versatile platforms for precision genome editing in a wide range of organisms. Here we have developed powerful CRISPR/Cas9 tools for marker-based and marker-free genome modifications in Penicillium chrysogenum, a model filamentous fungus and industrially

  11. CAS CERN Accelerator School vacuum technology. Proceedings

    International Nuclear Information System (INIS)

    Turner, S.

    1999-01-01

    These proceedings present the lectures given at the twelfth specialized course organized by the CERN Accelerator School (CAS), the topic this time being 'Vacuum Technology'. Despite the importance of vacuum technology in the design and operation of particle accelerators at CERN and at the many other accelerators already installed around the world, this was the first time that CAS has organized a course devoted entirely to this topic. Perhaps this reflects the facts that vacuum has become one of the more critical aspects of future accelerators, and that many of the pioneers in the accelerator field are being replaced by new, younger personnel. The lectures start with the basic concepts of the physics and technology of vacuum followed by detailed descriptions of the many different types of gas-pumping devices and methods to measure the pressures achieved. The outgassing characteristics of the different materials used in the construction of vacuum systems and the optimisation of cleaning methods to reduce this outgassing are then explained together with the effects of the residual gases on the particle beams. Then follow chapters on leak detection, materials and vacuum system engineering. Finally, seminars are presented on designing vacuum systems, the history of vacuum devices, the LHC (large hadron collider) vacuum system, vacuum systems for electron storage rings, and quality assurance for vacuum. (orig.)

  12. ISHKS joint registry: A preliminary report.

    Science.gov (United States)

    Pachore, Jawahir A; Vaidya, Shrinand V; Thakkar, Chandrasekhar J; Bhalodia, Haresh Kumar P; Wakankar, Hemant M

    2013-09-01

    Total knee arthroplasty (TKA) and total hip arthroplasty (THA) are the most widely practiced surgical options for arthritis all over the world and its application is rising in India. Indian Society of Hip and Knee Surgeons (ISHKS) has established a joints registry and has been collecting data for last 6 years. All members of ISHKS are encouraged to actively participate in the registry. A simple two page knee and hip form can be downloaded from the website www.ishks.com. The information collected includes patient demographics, indication for surgery, implant details and in case of revision arthroplasty: the details of implants removed and the cause of failure of primary arthroplasty. These forms are mailed to the central registry office and the data is fed in computerized registry. Data collection started in October 2006. Joint registry is a very important initiative of ISHKS and till date, have data of 34,478 TKAs and 3604 THAs, contributed by 42 surgeons across India. Some important observations have emerged. Data of 34,478 TKAs was assessed: These included 8612 males (25%) and 25,866 females (75%). Average age was 64.4 years (Osteoarthritis range: 45 to 88 years; Rheumatoid arthritis range: 22 to 74 years). Average body mass index was 29.1 (Range: 18.1 to 42.9). The indication for TKA was osteoarthritis in 33,444 (97%) and rheumatoid arthritis in 759 (2.2%). Total of 3604 THA procedures were recorded. These included 2162 (60%) male patients and 1442 (40%) female patients. Average age was 52 years (Range 17 to 85 years) and average BMI was 25.8 (Range: 17.3 to 38.5). The indications for THA was AVN in 49%. The registry will become more meaningful in years to come. Active participation of all arthroplasty surgeons across India is vital for the success of the joints registry.

  13. CRISPR-Cas Technologies and Applications in Food Bacteria.

    Science.gov (United States)

    Stout, Emily; Klaenhammer, Todd; Barrangou, Rodolphe

    2017-02-28

    Clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) proteins form adaptive immune systems that occur in many bacteria and most archaea. In addition to protecting bacteria from phages and other invasive mobile genetic elements, CRISPR-Cas molecular machines can be repurposed as tool kits for applications relevant to the food industry. A primary concern of the food industry has long been the proper management of food-related bacteria, with a focus on both enhancing the outcomes of beneficial microorganisms such as starter cultures and probiotics and limiting the presence of detrimental organisms such as pathogens and spoilage microorganisms. This review introduces CRISPR-Cas as a novel set of technologies to manage food bacteria and offers insights into CRISPR-Cas biology. It primarily focuses on the applications of CRISPR-Cas systems and tools in starter cultures and probiotics, encompassing strain-typing, phage resistance, plasmid vaccination, genome editing, and antimicrobial activity.

  14. Coaching and engaging. Developing teaching with CAS in High School

    DEFF Research Database (Denmark)

    Bang, Henrik Peter; Grønbæk, Niels; Larsen, Claus Richard

    The extensive use of CAS at upper secondary school in Denmark provides a laboratory for research on the development of standards for CAS teaching. The poster focuses on action research into teachers developing lessons and student activities in an ongoing collaboration between university and high ...... schools on use of CAS in mathematics teaching. Coaches1 mediate design processes, reflection and documentation, and enable sharing. We discuss coaching as a valuable part of action research, and how to draw findings from the collaboration.......The extensive use of CAS at upper secondary school in Denmark provides a laboratory for research on the development of standards for CAS teaching. The poster focuses on action research into teachers developing lessons and student activities in an ongoing collaboration between university and high...

  15. Exploiting CRISPR-Cas to manipulate Enterococcus faecalis populations.

    Science.gov (United States)

    Hullahalli, Karthik; Rodrigues, Marinelle; Palmer, Kelli L

    2017-06-23

    CRISPR-Cas provides a barrier to horizontal gene transfer in prokaryotes. It was previously observed that functional CRISPR-Cas systems are absent from multidrug-resistant (MDR) Enterococcus faecalis , which only possess an orphan CRISPR locus, termed CRISPR2, lacking cas genes. Here, we investigate how the interplay between CRISPR-Cas genome defense and antibiotic selection for mobile genetic elements shapes in vitro E. faecalis populations. We demonstrate that CRISPR2 can be reactivated for genome defense in MDR strains. Interestingly, we observe that E. faecalis transiently maintains CRISPR targets despite active CRISPR-Cas systems. Subsequently, if selection for the CRISPR target is present, toxic CRISPR spacers are lost over time, while in the absence of selection, CRISPR targets are lost over time. We find that forced maintenance of CRISPR targets induces a fitness cost that can be exploited to alter heterogeneous E. faecalis populations.

  16. Linked Registries: Connecting Rare Diseases Patient Registries through a Semantic Web Layer.

    Science.gov (United States)

    Sernadela, Pedro; González-Castro, Lorena; Carta, Claudio; van der Horst, Eelke; Lopes, Pedro; Kaliyaperumal, Rajaram; Thompson, Mark; Thompson, Rachel; Queralt-Rosinach, Núria; Lopez, Estrella; Wood, Libby; Robertson, Agata; Lamanna, Claudia; Gilling, Mette; Orth, Michael; Merino-Martinez, Roxana; Posada, Manuel; Taruscio, Domenica; Lochmüller, Hanns; Robinson, Peter; Roos, Marco; Oliveira, José Luís

    2017-01-01

    Patient registries are an essential tool to increase current knowledge regarding rare diseases. Understanding these data is a vital step to improve patient treatments and to create the most adequate tools for personalized medicine. However, the growing number of disease-specific patient registries brings also new technical challenges. Usually, these systems are developed as closed data silos, with independent formats and models, lacking comprehensive mechanisms to enable data sharing. To tackle these challenges, we developed a Semantic Web based solution that allows connecting distributed and heterogeneous registries, enabling the federation of knowledge between multiple independent environments. This semantic layer creates a holistic view over a set of anonymised registries, supporting semantic data representation, integrated access, and querying. The implemented system gave us the opportunity to answer challenging questions across disperse rare disease patient registries. The interconnection between those registries using Semantic Web technologies benefits our final solution in a way that we can query single or multiple instances according to our needs. The outcome is a unique semantic layer, connecting miscellaneous registries and delivering a lightweight holistic perspective over the wealth of knowledge stemming from linked rare disease patient registries.

  17. The Entity Registry System: Publishing and Consuming Linked Data in Poorly Connected Environments

    NARCIS (Netherlands)

    Guéret, Christophe; Cudré-Mauroux, Philippe

    2014-01-01

    Sixty-five percent of the world's population is deprived of ICT-enhanced data-sharing because of poor access to digital technology. The ExaScale Infolab and Data Archiving and Networked Services (DANS) have designed a new framework, the "Entity Registry System" (ERS), and produced a reference

  18. #DDOD Use Case: Improve National Death Registry for use with outcomes research

    Data.gov (United States)

    U.S. Department of Health & Human Services — SUMMARY DDOD use case request to improve National Death Registry for use with outcomes research. WHAT IS A USE CASE? A “Use Case” is a request that was made by the...

  19. The design and rationale of the primary angioplasty registry of Kerala

    Directory of Open Access Journals (Sweden)

    Jabir A

    2017-11-01

    Conclusions: The primary angioplasty registry of Kerala would help analyze the quality and outcomes of primary PCI services in Kerala, thereby yielding insights that can help limit unacceptable procedural variations in the performance of primary PCI. Identifying deviations from guideline based therapies can form the basis of quality improvement programs, which in turn will enable hospitals to achieve better patient outcomes.

  20. The relational clinical database: a possible solution to the star wars in registry systems.

    Science.gov (United States)

    Michels, D K; Zamieroski, M

    1990-12-01

    In summary, having data from other service areas available in a relational clinical database could resolve many of the problems existing in today's registry systems. Uniting sophisticated information systems into a centralized database system could definitely be a corporate asset in managing the bottom line.

  1. Not all predicted CRISPR-Cas systems are equal: isolated cas genes and classes of CRISPR like elements.

    Science.gov (United States)

    Zhang, Quan; Ye, Yuzhen

    2017-02-06

    The CRISPR-Cas systems in prokaryotes are RNA-guided immune systems that target and deactivate foreign nucleic acids. A typical CRISPR-Cas system consists of a CRISPR array of repeat and spacer units, and a locus of cas genes. The CRISPR and the cas locus are often located next to each other in the genomes. However, there is no quantitative estimate of the co-location. In addition, ad-hoc studies have shown that some non-CRISPR genomic elements contain repeat-spacer-like structures and are mistaken as CRISPRs. Using available genome sequences, we observed that a significant number of genomes have isolated cas loci and/or CRISPRs. We found that 11%, 22% and 28% of the type I, II and III cas loci are isolated (without CRISPRs in the same genomes at all or with CRISPRs distant in the genomes), respectively. We identified a large number of genomic elements that superficially reassemble CRISPRs but don't contain diverse spacers and have no companion cas genes. We called these elements false-CRISPRs and further classified them into groups, including tandem repeats and Staphylococcus aureus repeat (STAR)-like elements. This is the first systematic study to collect and characterize false-CRISPR elements. We demonstrated that false-CRISPRs could be used to reduce the false annotation of CRISPRs, therefore showing them to be useful for improving the annotation of CRISPR-Cas systems.

  2. Sulfonamide inhibition studies of two β-carbonic anhydrases from the ascomycete fungus Sordaria macrospora, CAS1 and CAS2.

    Science.gov (United States)

    Vullo, Daniela; Lehneck, Ronny; Pöggeler, Stefanie; Supuran, Claudiu T

    2018-12-01

    The two β-carbonic anhydrases (CAs, EC 4.2.1.1) recently cloned and purified from the ascomycete fungus Sordaria macrospora, CAS1 and CAS2, were investigated for their inhibition with a panel of 39 aromatic, heterocyclic, and aliphatic sulfonamides and one sulfamate, many of which are clinically used agents. CAS1 was efficiently inhibited by tosylamide, 3-fluorosulfanilamide, and 3-chlorosulfanilamide (K I s in the range of 43.2-79.6 nM), whereas acetazolamide, methazolamide, topiramate, ethoxzolamide, dorzolamide, and brinzolamide were medium potency inhibitors (K I s in the range of 360-445 nM). CAS2 was less sensitive to sulfonamide inhibitors. The best CAS2 inhibitors were 5-amino-1,3,4-thiadiazole-2-sulfonamide (the deacetylated acetazolamide precursor) and 4-hydroxymethyl-benzenesulfonamide, with K I s in the range of 48.1-92.5 nM. Acetazolamide, dorzolamide, ethoxzolamide, topiramate, sulpiride, indisulam, celecoxib, and sulthiame were medium potency CAS2 inhibitors (K I s of 143-857 nM). Many other sulfonamides showed affinities in the high micromolar range or were ineffective as CAS1/2 inhibitors. Small changes in the structure of the inhibitor led to important differences of the activity. As these enzymes may show applications for the removal of anthropically generated polluting gases, finding modulators of their activity may be crucial for designing environmental-friendly CO 2 capture processes.

  3. [Types of medical registries - definitions, methodological aspects and quality of the scientific work with registries].

    Science.gov (United States)

    Mathis-Edenhofer, Stefan; Piso, Brigitte

    2011-12-01

    This work presents a comprehensive list of registry definitions including broader and narrower definitions. Compared to each other different methodological issues can be identified. Some of these issues are common for all registry types; some can be assigned more easily to a specific registry type. Instruments for evaluating the quality of registers reflect many of the mentioned aspects. Generally, and especially at registers with a descriptive or exploratory research dimension it is important to consider their intended purpose and in about it was achieved. This includes, for instance, whether the purpose and the methodology are coordinated. From the start of registration an initiator should be - based on the purpose - aware of the methodological dimension of the registry. This helps to apply the correct type of the registry, the appropriate guidance and, ultimately, the arguments for the effort (cost-benefit ratio).

  4. Artificial Nutritional Support Registries: systematic review.

    Science.gov (United States)

    Castelló-Botía, I; Wanden-Berghe, C; Sanz-Valero, J

    2009-01-01

    The nutritional registries are data bases through which we obtain the information to understand the nutrition of populations. Several main nutrition societies of the world have these types of registries, outstanding the NADYA (Home artificial and Ambulatory nutrition) group in Spain. The object of this study is to determine by means of a systematic review, the existent scientific production in the international data bases referred to nutritional support registries. Descriptive transversal study of the results of a critical bibliographic research done in the bioscience data bases: MEDLINE, EMBASE, The Cochrane Library, ISI (Web of Sciences), LILACS, CINHAL. A total of 20 original articles related to nutritional registries were found and recovered. Eleven registries of eight countries were identified: Australia, Germany, Italy, Japan, Spain, Sweden, United Status and United Kingdom. The Price Index was of 65% and all the articles were published in the last 20 years. The Price Index highlights the innovativeness of this practice. The articles related to nutritional support are heterogeneous with respect to data and population, which exposes this as a limitation for a combined analysis.

  5. The National Mental Health Registry (NMHR).

    Science.gov (United States)

    Aziz, A A; Salina, A A; Abdul Kadir, A B; Badiah, Y; Cheah, Y C; Nor Hayati, A; Ruzanna, Z Z; Sharifah Suziah, S M; Chee, K Y

    2008-09-01

    The National Mental Health Registry (NMHR) collects information about patients with mental disorder in Malaysia. This information allows us to estimate the incidence of selected mental disorders, and to evaluate risk factors and treatment in the country. The National Mental Health Registry (NMHR) presented its first report in 2004, a year after its establishment. The report focused on schizophrenia as a pioneer project for the National Mental Health Registry. The development of the registry has progressed with data collected from government-based facilities, the academia and the private sector. The 2003-2005 report was recently published and distributed. Since then the registry has progressed to include suicides and other mental illnesses such as depression. The NMHR Report 2003-2005 provides detailed information about the profile of persons with Schizophrenia who presented for the first time to various psychiatry and mental health providers throughout Malaysia. More detailed description regarding pharmacotherapy is reported and few cross tabulations done in an effort to provide better understanding and more clinically meaningful reports.

  6. ISHKS joint registry: A preliminary report

    Directory of Open Access Journals (Sweden)

    Jawahir A Pachore

    2013-01-01

    form can be downloaded from the website www.ishks.com. The information collected includes patient demographics, indication for surgery, implant details and in case of revision arthroplasty: the details of implants removed and the cause of failure of primary arthroplasty. These forms are mailed to the central registry office and the data is fed in computerized registry. Data collection started in October 2006. Results: Joint registry is a very important initiative of ISHKS and till date, have data of 34,478 TKAs and 3604 THAs, contributed by 42 surgeons across India. Some important observations have emerged. Data of 34,478 TKAs was assessed: These included 8612 males (25% and 25,866 females (75%. Average age was 64.4 years (Osteoarthritis range: 45 to 88 years; Rheumatoid arthritis range: 22 to 74 years. Average body mass index was 29.1 (Range: 18.1 to 42.9. The indication for TKA was osteoarthritis in 33,444 (97% and rheumatoid arthritis in 759 (2.2%. Total of 3604 THA procedures were recorded. These included 2162 (60% male patients and 1442 (40% female patients. Average age was 52 years (Range 17 to 85 years and average BMI was 25.8 (Range: 17.3 to 38.5. The indications for THA was AVN in 49%. Conclusion: The registry will become more meaningful in years to come. Active participation of all arthroplasty surgeons across India is vital for the success of the joints registry.

  7. Interference activity of a minimal Type I CRISPR–Cas system from Shewanella putrefaciens

    Science.gov (United States)

    Dwarakanath, Srivatsa; Brenzinger, Susanne; Gleditzsch, Daniel; Plagens, André; Klingl, Andreas; Thormann, Kai; Randau, Lennart

    2015-01-01

    Type I CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)–Cas (CRISPR-associated) systems exist in bacterial and archaeal organisms and provide immunity against foreign DNA. The Cas protein content of the DNA interference complexes (termed Cascade) varies between different CRISPR-Cas subtypes. A minimal variant of the Type I-F system was identified in proteobacterial species including Shewanella putrefaciens CN-32. This variant lacks a large subunit (Csy1), Csy2 and Csy3 and contains two unclassified cas genes. The genome of S. putrefaciens CN-32 contains only five Cas proteins (Cas1, Cas3, Cas6f, Cas1821 and Cas1822) and a single CRISPR array with 81 spacers. RNA-Seq analyses revealed the transcription of this array and the maturation of crRNAs (CRISPR RNAs). Interference assays based on plasmid conjugation demonstrated that this CRISPR-Cas system is active in vivo and that activity is dependent on the recognition of the dinucleotide GG PAM (Protospacer Adjacent Motif) sequence and crRNA abundance. The deletion of cas1821 and cas1822 reduced the cellular crRNA pool. Recombinant Cas1821 was shown to form helical filaments bound to RNA molecules, which suggests its role as the Cascade backbone protein. A Cascade complex was isolated which contained multiple Cas1821 copies, Cas1822, Cas6f and mature crRNAs. PMID:26350210

  8. Interference activity of a minimal Type I CRISPR-Cas system from Shewanella putrefaciens.

    Science.gov (United States)

    Dwarakanath, Srivatsa; Brenzinger, Susanne; Gleditzsch, Daniel; Plagens, André; Klingl, Andreas; Thormann, Kai; Randau, Lennart

    2015-10-15

    Type I CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-Cas (CRISPR-associated) systems exist in bacterial and archaeal organisms and provide immunity against foreign DNA. The Cas protein content of the DNA interference complexes (termed Cascade) varies between different CRISPR-Cas subtypes. A minimal variant of the Type I-F system was identified in proteobacterial species including Shewanella putrefaciens CN-32. This variant lacks a large subunit (Csy1), Csy2 and Csy3 and contains two unclassified cas genes. The genome of S. putrefaciens CN-32 contains only five Cas proteins (Cas1, Cas3, Cas6f, Cas1821 and Cas1822) and a single CRISPR array with 81 spacers. RNA-Seq analyses revealed the transcription of this array and the maturation of crRNAs (CRISPR RNAs). Interference assays based on plasmid conjugation demonstrated that this CRISPR-Cas system is active in vivo and that activity is dependent on the recognition of the dinucleotide GG PAM (Protospacer Adjacent Motif) sequence and crRNA abundance. The deletion of cas1821 and cas1822 reduced the cellular crRNA pool. Recombinant Cas1821 was shown to form helical filaments bound to RNA molecules, which suggests its role as the Cascade backbone protein. A Cascade complex was isolated which contained multiple Cas1821 copies, Cas1822, Cas6f and mature crRNAs. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  9. Impact on outcome of different types of carotid stent: results from the European Registry of Carotid Artery Stenting.

    Science.gov (United States)

    Stabile, Eugenio; Giugliano, Giuseppe; Cremonesi, Alberto; Bosiers, Marc; Reimers, Bernhard; Setacci, Carlo; Cao, Piergiorgio; Schmidt, Andrej; Sievert, Horst; Peeters, Patrick; Nikas, Dimitrios; Sannino, Anna; de Donato, Gianmarco; Parlani, Giambattista; Castriota, Fausto; Hornung, Marius; Rubino, Paolo; Esposito, Giovanni; Tesorio, Tullio

    2016-06-12

    Conflicting data exist on the impact on outcome of the use of different stent types during carotid artery stenting (CAS). The aim of this study was to evaluate clinical outcomes according to different carotid stent design among the population of the European Registry of Carotid Artery Stenting (ERCAS). The present study was conducted in 1,604 patients who underwent neuroprotected CAS in ERCAS. All types of commercially available carotid stent were used. Open-cell design stents were classified according to free cell area into 7.5 mm2. A total of 713 closed-cell, 456 hybrid-cell, 238 7.5 mm2 open-cell stents were implanted. Overall, the 30-day stroke and death rate was 1.37%. At 30 days, 19 strokes occurred (1.18%): eight in the group of patients treated with a closed-cell (1.12%), two in those with a hybrid-cell (0.44%), three in those with a 7.5 mm2 open-cell stent (3.05%) (p=0.045). Data of the present study suggest that, in the setting of neuroprotected CAS performed in high-volume centres by properly trained operators, the use of an open-cell design stent with a free cell area >7.5 mm2 may be associated with an increased 30-day stroke risk.

  10. A Model-Driven, Science Data Product Registration Service

    Science.gov (United States)

    Hardman, S.; Ramirez, P.; Hughes, J. S.; Joyner, R.; Cayanan, M.; Lee, H.; Crichton, D. J.

    2011-12-01

    The Planetary Data System (PDS) has undertaken an effort to overhaul the PDS data architecture (including the data model, data structures, data dictionary, etc.) and to deploy an upgraded software system (including data services, distributed data catalog, etc.) that fully embraces the PDS federation as an integrated system while taking advantage of modern innovations in information technology (including networking capabilities, processing speeds, and software breakthroughs). A core component of this new system is the Registry Service that will provide functionality for tracking, auditing, locating, and maintaining artifacts within the system. These artifacts can range from data files and label files, schemas, dictionary definitions for objects and elements, documents, services, etc. This service offers a single reference implementation of the registry capabilities detailed in the Consultative Committee for Space Data Systems (CCSDS) Registry Reference Model White Book. The CCSDS Reference Model in turn relies heavily on the Electronic Business using eXtensible Markup Language (ebXML) standards for registry services and the registry information model, managed by the OASIS consortium. Registries are pervasive components in most information systems. For example, data dictionaries, service registries, LDAP directory services, and even databases provide registry-like services. These all include an account of informational items that are used in large-scale information systems ranging from data values such as names and codes, to vocabularies, services and software components. The problem is that many of these registry-like services were designed with their own data models associated with the specific type of artifact they track. Additionally these services each have their own specific interface for interacting with the service. This Registry Service implements the data model specified in the ebXML Registry Information Model (RIM) specification that supports the various

  11. Mr.CAS-A minimalistic (pure) Ruby CAS for fast prototyping and code generation

    Science.gov (United States)

    Ragni, Matteo

    There are Computer Algebra System (CAS) systems on the market with complete solutions for manipulation of analytical models. But exporting a model that implements specific algorithms on specific platforms, for target languages or for particular numerical library, is often a rigid procedure that requires manual post-processing. This work presents a Ruby library that exposes core CAS capabilities, i.e. simplification, substitution, evaluation, etc. The library aims at programmers that need to rapidly prototype and generate numerical code for different target languages, while keeping separated mathematical expression from the code generation rules, where best practices for numerical conditioning are implemented. The library is written in pure Ruby language and is compatible with most Ruby interpreters.

  12. The Danish National Acute Leukemia Registry

    DEFF Research Database (Denmark)

    Østgård, Lene Sofie Granfeldt; Nørgaard, Jan Maxwell; Raaschou-Jensen, Klas Kræsten

    2016-01-01

    AIM OF DATABASE: The main aim of the Danish National Acute Leukemia Registry (DNLR) was to obtain information about the epidemiology of the hematologic cancers acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome (MDS). STUDY POPULATION: The registry...... was established in January 2000 by the Danish Acute Leukemia Group and has been expanded over the years. It includes adult AML patients diagnosed in Denmark since 2000, ALL patients diagnosed since 2005, and MDS patients diagnosed since 2010. The coverage of leukemia patients exceeds 99%, and the coverage of MDS...... years. To ensure this high coverage, completeness, and quality of data, linkage to the Danish Civil Registration System and the Danish National Registry of Patients, and several programmed data entry checks are used. CONCLUSION: The completeness and positive predictive values of the leukemia data have...

  13. United States Transuranium and Uranium Registries

    International Nuclear Information System (INIS)

    Kathren, R.L.; Filipy, R.E.; Dietert, S.E.

    1991-06-01

    This report summarizes the primary scientific activities of the United States Transuranium and Uranium Registries for the period October 1, 1989 through September 30, 1990. The Registries are parallel human tissue research programs devoted to the study of the actinide elements in humans. To date there have been 261 autopsy or surgical specimen donations, which include 11 whole bodies. The emphasis of the Registry was directed towards quality improvement and the development of a fully computerized data base that would incorporate not only the results of postmortem radiochemical analysis, but also medical and monitoring information obtained during life. Human subjects reviews were also completed. A three compartment biokinetic model for plutonium distribution is proposed. 2 tabs

  14. An international registry for primary ciliary dyskinesia

    DEFF Research Database (Denmark)

    Werner, Claudius; Lablans, Martin; Ataian, Maximilian

    2016-01-01

    Primary ciliary dyskinesia (PCD) is a rare autosomal recessive disorder leading to chronic upper and lower airway disease. Fundamental data on epidemiology, clinical presentation, course and treatment strategies are lacking in PCD. We have established an international PCD registry to realise...... an unmet need for an international platform to systematically collect data on incidence, clinical presentation, treatment and disease course.The registry was launched in January 2014. We used internet technology to ensure easy online access using a web browser under www.pcdregistry.eu. Data from 201...... methods in addition to classical clinical symptoms. Preliminary analysis of lung function data demonstrated a mean annual decline of percentage predicted forced expiratory volume in 1 s of 0.59% (95% CI 0.98-0.22).Here, we present the development of an international PCD registry as a new promising tool...

  15. CAS Introduction to Accelerator Physics in Spain

    CERN Multimedia

    CERN Bulletin

    2012-01-01

    The CERN Accelerator School (CAS) and the University of Granada jointly organised a course called "Introduction to Accelerator Physics" in Granada, Spain, from 28 October to 9 November, 2012.   The course attracted over 200 applicants, of whom 139 were selected to attend. The students were of 25 different nationalities, coming from countries as far away as Australia, China, Guatemala and India. The intensive programme comprised 38 lectures, 3 seminars, 4 tutorials where the students were split into three groups, a poster session and 7 hours of guided and private study. Feedback from the students was very positive, praising the expertise of the lecturers, as well as the high standard and quality of their lectures. CERN's Director-General, Rolf Heuer, gave a public lecture at the Parque de las Ciencias entitled "The Large Hadron Collider: Unveiling the Universe". In addition to the academic programme, the students had the opportunity to visit the well...

  16. The ultraviolet variations of iota Cas

    Science.gov (United States)

    Molnar, M. R.; Mallama, A. D.; Soskey, D. G.; Holm, A. V.

    1976-01-01

    The Ap variable star iota Cas was observed with the photometers on OAO-2 covering the spectral range 1430-4250 A. The ultraviolet light curves show a double wave with primary minimum and maximum at phase ? 0.00 and 0.35, respectively. Secondary minimum light is at phase ? 0.65 with secondary maximum at phase ? 0.85. The light curves longward of 3150 A vary in opposition to those shortward of this 'null region'. Ground-based coude spectra show that the Fe II and Cr II line strengths have a double-wave variation such that maximum strength occurs at minimum ultraviolet light. We suggest that the strong ultraviolet opacities due to photoionization and line blanketing by these metals may cause the observed photometric variations. We have also constructed an oblique-rotator model which shows iron and chromium lying in a great circle band rather than in circular spots.

  17. CAS Accelerator Physics held in Erice, Italy

    CERN Multimedia

    CERN Accelerator School

    2013-01-01

    The CERN Accelerator School (CAS) recently organised a specialised course on Superconductivity for Accelerators, held at the Ettore Majorana Foundation and Centre for Scientific Culture in Erice, Italy from 24 April-4 May, 2013.   Photo courtesy of Alessandro Noto, Ettore Majorana Foundation and Centre for Scientific Culture. Following a handful of summary lectures on accelerator physics and the fundamental processes of superconductivity, the course covered a wide range of topics related to superconductivity and highlighted the latest developments in the field. Realistic case studies and topical seminars completed the programme. The school was very successful with 94 participants representing 23 nationalities, coming from countries as far away as Belorussia, Canada, China, India, Japan and the United States (for the first time a young Ethiopian lady, studying in Germany, attended this course). The programme comprised 35 lectures, 3 seminars and 7 hours of case study. The case studies were p...

  18. CAS Accelerator Physics (Ion Sources) in Slovakia

    CERN Multimedia

    CAS School

    2012-01-01

    The CERN Accelerator School (CAS) and the Slovak University of Technology jointly organised a specialised course on ion sources, held at the Hotel Senec, Senec, Slovakia, from 29 May to 8 June, 2012.   Following some background lectures on accelerator physics and the fundamental processes of atomic and plasma physics, the course covered a wide range of topics related to ion sources and highlighted the latest developments in the field. Realistic case studies and topical seminars completed the programme. The school was very successful, with 69 participants representing 25 nationalities. Feedback from the participants was extremely positive, reflecting the high standard of the lectures. The case studies were performed with great enthusiasm and produced some excellent results. In addition to the academic programme, the participants were able to take part in a one-day excursion consisting of a guided tour of Bratislava and free time. A welcome event was held at the Hotel Senec, with s...

  19. CAS course on Plasma Wake Acceleration

    CERN Multimedia

    CERN Accelerator School

    2015-01-01

    The CERN Accelerator School (CAS) recently organised a specialised course on Plasma Wake Acceleration, held at CERN, Geneva, Switzerland, from 23 to 29 November 2014.    Following a number of introductory lectures on laser and plasma physics, as well as an overview of conventional accelerators and their limitations, the course covered a large number of aspects of plasma wake acceleration schemes: the creation of plasma by high power lasers or particle beams, a description of the plasma creation process through simulations and the characteristics of the accelerated particle beams, including results of the latest achievements. Lectures on beam diagnostics, the applications of plasma accelerated beams, and topical seminars completed the programme.  The course was very successful, with 109 students of 26 nationalities attending; most participants coming from European counties, but also from the US, Israel, India, South Korea, Russia and Ukraine. Feedback from the participants was...

  20. Adaptation in CRISPR-Cas Systems.

    Science.gov (United States)

    Sternberg, Samuel H; Richter, Hagen; Charpentier, Emmanuelle; Qimron, Udi

    2016-03-17

    Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) proteins constitute an adaptive immune system in prokaryotes. The system preserves memories of prior infections by integrating short segments of foreign DNA, termed spacers, into the CRISPR array in a process termed adaptation. During the past 3 years, significant progress has been made on the genetic requirements and molecular mechanisms of adaptation. Here we review these recent advances, with a focus on the experimental approaches that have been developed, the insights they generated, and a proposed mechanism for self- versus non-self-discrimination during the process of spacer selection. We further describe the regulation of adaptation and the protein players involved in this fascinating process that allows bacteria and archaea to harbor adaptive immunity. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. CAS medium-size nuclear plants

    International Nuclear Information System (INIS)

    Vogelweith, L.; Weiss, A.

    1977-01-01

    CEA has developed a range of pressurized water reactors of the type CAS Compact, which are adapted to civil ship propulsion, or to electric power production, combined possibly with heat production, up to outputs equivalent to 125MW(e). Nuclear plants equipped with these reactors are suitable for medium-size electric networks, especially in developing countries, because they are easily adaptable, owing to their flexibility; they can be installed and used in a variety of ways (on land, floating installation, combination of electric power and other production, etc.); they can be used as training reactors by countries wishing to limit their investment plans before undertaking a wider nuclear development. Examples of two possible realizations are presented: as a floating plant, and as a combined electric and desalting plant. (author)

  2. Nucleosome breathing and remodeling constrain CRISPR-Cas9 function

    Science.gov (United States)

    Isaac, R Stefan; Jiang, Fuguo; Doudna, Jennifer A; Lim, Wendell A; Narlikar, Geeta J; Almeida, Ricardo

    2016-01-01

    The CRISPR-Cas9 bacterial surveillance system has become a versatile tool for genome editing and gene regulation in eukaryotic cells, yet how CRISPR-Cas9 contends with the barriers presented by eukaryotic chromatin is poorly understood. Here we investigate how the smallest unit of chromatin, a nucleosome, constrains the activity of the CRISPR-Cas9 system. We find that nucleosomes assembled on native DNA sequences are permissive to Cas9 action. However, the accessibility of nucleosomal DNA to Cas9 is variable over several orders of magnitude depending on dynamic properties of the DNA sequence and the distance of the PAM site from the nucleosome dyad. We further find that chromatin remodeling enzymes stimulate Cas9 activity on nucleosomal templates. Our findings imply that the spontaneous breathing of nucleosomal DNA together with the action of chromatin remodelers allow Cas9 to effectively act on chromatin in vivo. DOI: http://dx.doi.org/10.7554/eLife.13450.001 PMID:27130520

  3. CRISPR/Cas9 for cancer research and therapy.

    Science.gov (United States)

    Zhan, Tianzuo; Rindtorff, Niklas; Betge, Johannes; Ebert, Matthias P; Boutros, Michael

    2018-04-16

    CRISPR/Cas9 has become a powerful method for making changes to the genome of many organisms. First discovered in bacteria as part of an adaptive immune system, CRISPR/Cas9 and modified versions have found a widespread use to engineer genomes and to activate or to repress the expression of genes. As such, CRISPR/Cas9 promises to accelerate cancer research by providing an efficient technology to dissect mechanisms of tumorigenesis, identify targets for drug development, and possibly arm cells for cell-based therapies. Here, we review current applications of the CRISPR/Cas9 technology for cancer research and therapy. We describe novel Cas9 variants and how they are used in functional genomics to discover novel cancer-specific vulnerabilities. Furthermore, we highlight the impact of CRISPR/Cas9 in generating organoid and mouse models of cancer. Finally, we provide an overview of the first clinical trials that apply CRISPR/Cas9 as a therapeutic approach against cancer. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. CRISPR/Cas9 in Genome Editing and Beyond.

    Science.gov (United States)

    Wang, Haifeng; La Russa, Marie; Qi, Lei S

    2016-06-02

    The Cas9 protein (CRISPR-associated protein 9), derived from type II CRISPR (clustered regularly interspaced short palindromic repeats) bacterial immune systems, is emerging as a powerful tool for engineering the genome in diverse organisms. As an RNA-guided DNA endonuclease, Cas9 can be easily programmed to target new sites by altering its guide RNA sequence, and its development as a tool has made sequence-specific gene editing several magnitudes easier. The nuclease-deactivated form of Cas9 further provides a versatile RNA-guided DNA-targeting platform for regulating and imaging the genome, as well as for rewriting the epigenetic status, all in a sequence-specific manner. With all of these advances, we have just begun to explore the possible applications of Cas9 in biomedical research and therapeutics. In this review, we describe the current models of Cas9 function and the structural and biochemical studies that support it. We focus on the applications of Cas9 for genome editing, regulation, and imaging, discuss other possible applications and some technical considerations, and highlight the many advantages that CRISPR/Cas9 technology offers.

  5. CRISPR/Cas9 Based Genome Editing of Penicillium chrysogenum.

    Science.gov (United States)

    Pohl, C; Kiel, J A K W; Driessen, A J M; Bovenberg, R A L; Nygård, Y

    2016-07-15

    CRISPR/Cas9 based systems have emerged as versatile platforms for precision genome editing in a wide range of organisms. Here we have developed powerful CRISPR/Cas9 tools for marker-based and marker-free genome modifications in Penicillium chrysogenum, a model filamentous fungus and industrially relevant cell factory. The developed CRISPR/Cas9 toolbox is highly flexible and allows editing of new targets with minimal cloning efforts. The Cas9 protein and the sgRNA can be either delivered during transformation, as preassembled CRISPR-Cas9 ribonucleoproteins (RNPs) or expressed from an AMA1 based plasmid within the cell. The direct delivery of the Cas9 protein with in vitro synthesized sgRNA to the cells allows for a transient method for genome engineering that may rapidly be applicable for other filamentous fungi. The expression of Cas9 from an AMA1 based vector was shown to be highly efficient for marker-free gene deletions.

  6. Engineering Plant Immunity via CRISPR/Cas13a System

    KAUST Repository

    Aljedaani, Fatimah R.

    2018-05-01

    Viral diseases constitute a major threat to the agricultural production and food security throughout the world. Plants cope with the invading viruses by triggering immune responses and small RNA interference (RNAi) systems. In prokaryotes, CRISPR/Cas systems function as an adaptive immune system to provide bacteria with resistance against invading phages and conjugative plasmids. Interestingly, CRISPR/Cas9 system was shown to interfere with eukaryotic DNA viruses and confer resistance against plant DNA viruses. The majority of the plant viruses have RNA genomes. The aim of this study is to test the ability of the newly discovered CRISPR/Cas13a immune system, that targets and cleaves single stranded RNA (ssRNA) in prokaryotes, to provide resistance against RNA viruses in plants. Here, I employ the CRISPR/Cas13a system for molecular interference against Turnip Mosaic Virus (TuMV), a plant RNA virus. The results of this study established the CRISPR/Cas13a as a molecular interference machinery against RNA viruses in plants. Specifically, my data show that the CRISPR/Cas13a machinery is able to interfere with and degrade the TuMV (TuMV-GFP) RNA genome. In conclusion, these data indicate that the CRISPR/Cas13 systems can be employed for engineering interference and durable resistance against RNA viruses in diverse plant species.

  7. CRISPR/Cas9-mediated viral interference in plants

    KAUST Repository

    Ali, Zahir

    2015-11-11

    Background The CRISPR/Cas9 system provides bacteria and archaea with molecular immunity against invading phages and conjugative plasmids. Recently, CRISPR/Cas9 has been used for targeted genome editing in diverse eukaryotic species. Results In this study, we investigate whether the CRISPR/Cas9 system could be used in plants to confer molecular immunity against DNA viruses. We deliver sgRNAs specific for coding and non-coding sequences of tomato yellow leaf curl virus (TYLCV) into Nicotiana benthamiana plants stably overexpressing the Cas9 endonuclease, and subsequently challenge these plants with TYLCV. Our data demonstrate that the CRISPR/Cas9 system targeted TYLCV for degradation and introduced mutations at the target sequences. All tested sgRNAs exhibit interference activity, but those targeting the stem-loop sequence within the TYLCV origin of replication in the intergenic region (IR) are the most effective. N. benthamiana plants expressing CRISPR/Cas9 exhibit delayed or reduced accumulation of viral DNA, abolishing or significantly attenuating symptoms of infection. Moreover, this system could simultaneously target multiple DNA viruses. Conclusions These data establish the efficacy of the CRISPR/Cas9 system for viral interference in plants, thereby extending the utility of this technology and opening the possibility of producing plants resistant to multiple viral infections.

  8. Common variables in European pancreatic cancer registries

    DEFF Research Database (Denmark)

    De Leede, E. M.; Sibinga Mulder, B. G.; Bastiaannet, E.

    2016-01-01

    Background Quality assurance of cancer care is of utmost importance to detect and avoid under and over treatment. Most cancer data are collected by different procedures in different countries, and are poorly comparable at an international level. EURECCA, acronym for European Registration of Cancer...... registries, as well as specific pancreatic cancer audits/registries, were invited to participate in EURECCA Pancreas. Participating countries were requested to share an overview of their collected data items. Of the received datasets, a shared items list was made which creates insight in similarities between...

  9. The Danish Neuro-Oncology Registry

    DEFF Research Database (Denmark)

    Hansen, Steinbjørn; Nielsen, Jan; Laursen, René J

    2016-01-01

    BACKGROUND: The Danish Neuro-Oncology Registry (DNOR) is a nationwide clinical cancer database that has prospectively registered data on patients with gliomas since January 2009. The purpose of this study was to describe the establishment of the DNOR and further to evaluate the database completen......BACKGROUND: The Danish Neuro-Oncology Registry (DNOR) is a nationwide clinical cancer database that has prospectively registered data on patients with gliomas since January 2009. The purpose of this study was to describe the establishment of the DNOR and further to evaluate the database...

  10. Tumeur de Frantz: deux nouveaux cas

    Science.gov (United States)

    Bellarbi, Salma; Sina, Mohamed; Jahid, Ahmed; Zouaidia, Fouad; Bernoussi, Zakia; Mahassini, Najat

    2013-01-01

    A travers cet article, nous détaillons les caractéristiques clinico-pathologiques et discutons l'histogenèse de la tumeur de Frantz. Deux patients opérés pour tumeur de Frantz. Ils ont eu un traitement chirurgical seul. L'étude morphologique était couplée à un examen immuno-histochimique (IHC) utilisant les anticorps anti CD10, anti- vimentine, anti-énolase neuronale spécifique (NSE), anti-synaptophysine, anti-chromogranine A et anti-cytokératine. Un immuno-marquage à l'anti-oestrogène et l'anti-progestérone a été réalisé dans un cas. Il s'agissait d'une femme âgée de 45ans et d'un garçon de 12 ans. Les aspects échographiques et scannographiques étaient non spécifiques. Une exérèse chirurgicale complète a été réalisée dans les deux cas. L'analyse histologique évoquait une tumeur de Frantz. Le diagnostic a été retenu après étude immuno-histohimique. L'évolution était favorable sans récidive avec respectivement un recul de 18 et 16 mois. La tumeur de Frantz est une entité rare. Son diagnostic repose sur l'examen anatomopathologique complété par l'étude immuno-histochimique. Son pronostic est excellent après résection chirurgicale. PMID:23503717

  11. A web-based, patient driven registry for Angelman syndrome: the global Angelman syndrome registry.

    Science.gov (United States)

    Napier, Kathryn R; Tones, Megan; Simons, Chloe; Heussler, Helen; Hunter, Adam A; Cross, Meagan; Bellgard, Matthew I

    2017-08-01

    Angelman syndrome (AS) is a rare neurodevelopmental disorder that is characterised by severe global developmental delays, ataxia, loss of speech, epilepsy, sleep disorders, and a happy disposition. There is currently no cure for AS, though several pharmaceutical companies are anticipating drug trials for new therapies to treat AS. The Foundation for Angelman Therapeutics (FAST) Australia therefore identified a need for a global AS patient registry to identify patients for recruitment for clinical trials.The Global AS Registry was deployed in September 2016 utilising the Rare Disease Registry Framework, an open-source tool that enables the efficient creation and management of patient registries. The Global AS Registry is web-based and allows parents and guardians worldwide to register, provide informed consent, and enter data on individuals with AS. 286 patients have registered in the first 8 months since deployment.We demonstrate the successful deployment of the first patient-driven global registry for AS. The data generated from the Global AS Registry will be crucial in identifying patients suitable for clinical trials and in informing research that will identify treatments for AS, and ultimately improve the lives of individuals and their families living with AS.

  12. Programmable RNA recognition and cleavage by CRISPR/Cas9.

    Science.gov (United States)

    O'Connell, Mitchell R; Oakes, Benjamin L; Sternberg, Samuel H; East-Seletsky, Alexandra; Kaplan, Matias; Doudna, Jennifer A

    2014-12-11

    The CRISPR-associated protein Cas9 is an RNA-guided DNA endonuclease that uses RNA-DNA complementarity to identify target sites for sequence-specific double-stranded DNA (dsDNA) cleavage. In its native context, Cas9 acts on DNA substrates exclusively because both binding and catalysis require recognition of a short DNA sequence, known as the protospacer adjacent motif (PAM), next to and on the strand opposite the twenty-nucleotide target site in dsDNA. Cas9 has proven to be a versatile tool for genome engineering and gene regulation in a large range of prokaryotic and eukaryotic cell types, and in whole organisms, but it has been thought to be incapable of targeting RNA. Here we show that Cas9 binds with high affinity to single-stranded RNA (ssRNA) targets matching the Cas9-associated guide RNA sequence when the PAM is presented in trans as a separate DNA oligonucleotide. Furthermore, PAM-presenting oligonucleotides (PAMmers) stimulate site-specific endonucleolytic cleavage of ssRNA targets, similar to PAM-mediated stimulation of Cas9-catalysed DNA cleavage. Using specially designed PAMmers, Cas9 can be specifically directed to bind or cut RNA targets while avoiding corresponding DNA sequences, and we demonstrate that this strategy enables the isolation of a specific endogenous messenger RNA from cells. These results reveal a fundamental connection between PAM binding and substrate selection by Cas9, and highlight the utility of Cas9 for programmable transcript recognition without the need for tags.

  13. CRISPR/Cas9 advances engineering of microbial cell factories

    DEFF Research Database (Denmark)

    Jakociunas, Tadas; Jensen, Michael Krogh; Keasling, Jay D.

    2016-01-01

    interspaced palindromic repeats (CRISPR) and its associated proteins (Cas) have become the method of choice for precision genome engineering in many organisms due to their orthogonality, versatility and efficacy. Here we review the strategies adopted for implementation of RNA-guided CRISPR/Cas9 genome editing......-RNAs will be highlighted. Finally, this review will provide a perspective on the immediate challenges and opportunities foreseen by the use of CRISPR/Cas9 genome engineering and regulation in the context of metabolic engineering....

  14. Optimizing CRISPR/Cas9 for the Diatom Phaeodactylum tricornutum

    Directory of Open Access Journals (Sweden)

    Daniel Stukenberg

    2018-06-01

    Full Text Available CRISPR/Cas9 is a powerful tool for genome editing. We constructed an easy-to-handle expression vector for application in the model organism Phaeodactylum tricornutum and tested its capabilities in order to apply CRISPR/Cas9 technology for our purpose. In our experiments, we targeted two different genes, screened for mutations and analyzed mutated diatoms in a three-step process. In the end, we identified cells, showing either monoallelic or homo-biallelic targeted mutations. Thus, we confirm that application of the CRISPR/Cas9 system for P. tricornutum is very promising, although, as discussed, overlooked pitfalls have to be considered.

  15. Utilisation of diagnostic computerised tomography imaging and immediate clinical outcomes in older people with stroke before and after introduction of the National Service Framework for older people. A comparative study of hospital-based stroke registry data (1997-2003): Norfolk experience.

    Science.gov (United States)

    Myint, Phyo K; Vowler, Sarah L; Redmayne, Oliver; Fulcher, Robert A

    2006-07-01

    how the National Service Framework (NSF) for older people in England might be associated with changes in clinically relevant stroke outcome has not been investigated. We looked for changes in computerised tomography (CT) scan rate, inpatient case-fatality rate (CFR), length of acute hospital stay and discharge destination for older people with stroke, compared with their younger counterparts, for a period before, and after, the introduction of the NSF. two periods, 4 years before and 2 years after the publication of the NSF, were selected to compare the above outcomes between three age categories: or = 85 years of age. Annual summary data for these periods were compared for the magnitude of changes in all age categories for all outcomes measured between pre- and post-NSF periods. n = 5,219. Utilisation of CT imaging had increased in all age groups post-NSF, with the most significant improvement in the oldest group. This change was associated with a greater proportion of people who had CT in this age group being discharged home in the post-NSF period. There was no change in the mortality from stroke in any age group during the study. Although the length of acute hospital stay increased, this was associated with a higher percentage of home discharges particularly in > 65-year olds, suggesting better clinical outcome in those who survived. in this single-centre analysis, the post-NSF period appeared to be associated with improvement in outcome in older people with stroke. Continual monitoring using stroke registry data may help to assess whether these effects are sustained in the longer term.

  16. Department of Defense Birth and Infant Health Registry: select reproductive health outcomes, 2003-2014.

    Science.gov (United States)

    Bukowinski, Anna T; Conlin, Ava Marie S; Gumbs, Gia R; Khodr, Zeina G; Chang, Richard N; Faix, Dennis J

    2017-11-01

    Established following a 1998 directive, the Department of Defense Birth and Infant Health Registry (Registry) team conducts surveillance of select reproductive health outcomes among military families. Data are compiled from the Military Health System Data Repository and Defense Manpower Data Center to define the Registry cohort and outcomes of interest. Outcomes are defined using ICD-9/ICD-10 and Current Procedural Terminology codes, and include: pregnancy outcomes (e.g., live births, losses), birth defects, preterm births, and male:female infant sex ratio. This report includes data from 2003-2014 on 1,304,406 infants among military families and 258,332 pregnancies among active duty women. Rates of common adverse infant and pregnancy outcomes were comparable to or lower than those in the general US population. These observations, along with prior Registry analyses, provide reassurance that military service is not independently associated with increased risks for select adverse reproductive health outcomes. The Registry's diverse research portfolio demonstrates its unique capabilities to answer a wide range of questions related to reproductive health. These data provide the military community with information to identify successes and areas for improvement in prevention and care.

  17. 78 FR 69414 - Toxic Substances Control Act Chemical Testing; Receipt of Test Data

    Science.gov (United States)

    2013-11-19

    ...; Acute emulsion polymerization in Inhalation Toxicity in paper, textile, fiber, and Rats; Bacterial.../ Reproduction Development Toxicity. Note: CAS No. = Chemical Abstracts Service Registry Number. Authority: 15 U...

  18. Centralisation, décentralisation et accès aux services urbains : le cas de l’enlèvement des ordures ménagères à Abidjan Centralization, decentralization, access to urban public services : waste collection in Abidjan

    Directory of Open Access Journals (Sweden)

    Amandine Henry

    2013-03-01

    Full Text Available Cet article traite de l’inégalité d’accès aux services publics urbains dans les pays en développement et, plus particulièrement, de la question de l’accès au service d’enlèvement des ordures ménagères à Abidjan. Cette question est étroitement liée au mouvement de centralisation, décentralisation et recentralisation qui a affecté la gestion de ce service au cours des dernières décennies. Chaque étape de l’avancée de la Côte d’Ivoire dans le processus de décentralisation a provoqué des changements institutionnels dans la gestion des ordures ménagères à Abidjan ; tous ont eu des effets spécifiques sur l’accès de la population à ce service. Ces effets sont étudiés à l’échelle des communes et des quartiers à travers une enquête de terrain, et sont liés aux caractéristiques socio-économiques des quartiers. Une analyse comparative entre deux communes de standing opposé, ainsi que l’examen des aspects historiques de la problématique, s’attachent à identifier les facteurs-clés d’une telle inégalité d’accès au service d’enlèvement des ordures ménagères à Abidjan.This paper deals with the inequality of access to the urban public utilities in developing countries, and more accurately with the issue of the access to the waste collection in Abidjan. This question is closely linked with the centralization, decentralization and recentralization movements that affected this service management for the last decades. Each stage of the decentralization process in Ivory Coast brought institutional changes in waste collection management in Abidjan. Each of them had specific consequences on the access of people to this service. These consequences are investigated on a local scale and are linked to the socio-economic characteristics of the studied areas. Together with the focus on the historical aspects of the problematic, a comparative analysis between two districts of opposite standing attempts

  19. A guild of 45 CRISPR-associated (Cas protein families and multiple CRISPR/Cas subtypes exist in prokaryotic genomes.

    Directory of Open Access Journals (Sweden)

    Daniel H Haft

    2005-11-01

    Full Text Available Clustered regularly interspaced short palindromic repeats (CRISPRs are a family of DNA direct repeats found in many prokaryotic genomes. Repeats of 21-37 bp typically show weak dyad symmetry and are separated by regularly sized, nonrepetitive spacer sequences. Four CRISPR-associated (Cas protein families, designated Cas1 to Cas4, are strictly associated with CRISPR elements and always occur near a repeat cluster. Some spacers originate from mobile genetic elements and are thought to confer "immunity" against the elements that harbor these sequences. In the present study, we have systematically investigated uncharacterized proteins encoded in the vicinity of these CRISPRs and found many additional protein families that are strictly associated with CRISPR loci across multiple prokaryotic species. Multiple sequence alignments and hidden Markov models have been built for 45 Cas protein families. These models identify family members with high sensitivity and selectivity and classify key regulators of development, DevR and DevS, in Myxococcus xanthus as Cas proteins. These identifications show that CRISPR/cas gene regions can be quite large, with up to 20 different, tandem-arranged cas genes next to a repeat cluster or filling the region between two repeat clusters. Distinctive subsets of the collection of Cas proteins recur in phylogenetically distant species and correlate with characteristic repeat periodicity. The analyses presented here support initial proposals of mobility of these units, along with the likelihood that loci of different subtypes interact with one another as well as with host cell defensive, replicative, and regulatory systems. It is evident from this analysis that CRISPR/cas loci are larger, more complex, and more heterogeneous than previously appreciated.

  20. The Danish National Acute Leukemia Registry

    DEFF Research Database (Denmark)

    Østgård, Lene Sofie Granfeldt; Nørgaard, Jan Maxwell; Raaschou-Jensen, Klas Kræsten

    2016-01-01

    years. To ensure this high coverage, completeness, and quality of data, linkage to the Danish Civil Registration System and the Danish National Registry of Patients, and several programmed data entry checks are used. CONCLUSION: The completeness and positive predictive values of the leukemia data have...

  1. Validation of the Netherlands pacemaker patient registry

    NARCIS (Netherlands)

    Dijk, WA; Kingma, T; Hooijschuur, CAM; Dassen, WRM; Hoorntje, JCA; van Gelder, LM

    1997-01-01

    This paper deals with the validation of the information stored in the Netherlands central pacemaker patient database. At this moment the registry database contains information on more than 70500 patients, 85000 pacemakers and 90000 leads. The validation procedures consisted of an internal

  2. Costing Tool for International Cancer Registries

    Centers for Disease Control (CDC) Podcasts

    2016-11-21

    A health economist at CDC talks about a new tool for estimating how much it costs to run cancer registries in developing countries.  Created: 11/21/2016 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 11/21/2016.

  3. Airborne Hazards and Open Burn Pit Registry

    Science.gov (United States)

    ... this problem if you are in a high security environment where this is disabled by a network policy. The Registry will work in JavaScript-enabled browsers such as: Google Chrome 17+ Mozilla Firefox 12+ Internet Explorer 10+ Safari 5+ Safari iOS 5+ Android 2.3+ If you are using a compatible ...

  4. [History of the cancer registry in Mexico].

    Science.gov (United States)

    Allende-López, Aldo; Fajardo-Gutiérrez, Arturo

    2011-01-01

    A cancer registry is to record the data which let us to know the epidemiology of neoplasm, but led us take a decision in medical policy about this health problem that benefit patients. In this paper we did a brief historical review about models and attempts for having a cancer registry in Mexico. However, since 1940 "the fight against cancer" was declared, we have not had a confident cancer registry today validated and built with data from whole the country. In 1982, the Registro Nacional del Cancer was created. The design and validation of a registration card in four hospitals were the main results. In 1988, the Registro Nacional del Cancer was reinforced with a computerized system for facilitation the data capture. In 1994, it was signed the first interinstitutional agreement that led to Registro Histopatol6gico de Neoplasias Malignas. In 1996, the Instituto Mexicano del Seguro Social established a cancer registry in children in Mexico with the intention to have data from this population.

  5. 50 CFR 600.1410 - Registry process.

    Science.gov (United States)

    2010-10-01

    ... United States § 600.1410 Registry process. (a) A person may register through the NMFS web site at www... state registration or U.S. Coast Guard documentation number; home port or principal area of operation... website. (b) Individuals must submit their name; address; telephone number; date of birth; region(s) of...

  6. Correlating Orphaned Windows Registry Data Structures

    Directory of Open Access Journals (Sweden)

    Damir Kahved

    2009-06-01

    Full Text Available Recently, it has been shown that deleted entries of the Microsoft Windows registry (keys may still reside in the system files once the entries have been deleted from the active database. Investigating the complete keys in context may be extremely important from both a Forensic Investigation point of view and a legal point of view where a lack of context can bring doubt to an argument. In this paper we formalise the registry behaviour and show how a retrieved value may not maintain a relation to the part of the registry it belonged to and hence lose that context. We define registry orphans and elaborate on how they can be created inadvertently during software uninstallation and other system processes. We analyse the orphans and attempt to reconstruct them automatically. We adopt a data mining approach and introduce a set of attributes that can be applied by the forensic investigator to match values to their parents. The heuristics are encoded in a Decision Tree that can discriminate between keys and select those which most likely owned a particular orphan value.

  7. The Savant Syndrome Registry: A Preliminary Report.

    Science.gov (United States)

    Treffert, Darold A; Rebedew, David L

    2015-08-01

    A registry has been established to document certain characteristics on a sizeable worldwide sample of individuals with savant syndrome, a rare but remarkable condition in which persons with developmental disabilities, brain injury, or brain disease have some spectacular "islands" of skill or ability that stand in jarring, marked contrast to overall handicap. Of the 319 savants included in the registry, 90% are congenital savants, while 10% are acquired savants. The registry includes individuals from 33 countries, with 70% from the United States or Canada. Sex distribution was 79% male vs. 21% female (4:1). This report summarizes the findings in the congenital savant syndrome category of the registry. Among the individuals with congenital savant syndrome, the most common underlying disability was Autistic Spectrum Disorder (75%); various other central nervous system (CNS) disorders were present in the other 25%. Fifty-five percent possessed a single special skill, while 45% had multiple skills. Music was the most frequent principal skill followed by art, memory, mathematics, calendar calculating, language, visual-spatial/mechanical, athletic, computer, extrasensory perception, and other skills.

  8. Mexican registry of pulmonary hypertension: REMEHIP.

    Science.gov (United States)

    Sandoval Zarate, Julio; Jerjes-Sanchez, Carlos; Ramirez-Rivera, Alicia; Zamudio, Tomas Pulido; Gutierrez-Fajardo, Pedro; Elizalde Gonzalez, Jose; Leon, Mario Seoane Garcia De; Gamez, Miguel Beltran; Abril, Francisco Moreno Hoyos; Michel, Rodolfo Parra; Aguilar, Humberto Garcia

    REMEHIP is a prospective, multicentre registry on pulmonary hypertension. The main objective will be to identify the clinical profile, medical care, therapeutic trends and outcomes in adult and pediatric Mexican patients with well-characterized pulmonary hypertension. REMEHIP a multicenter registry began in 2015 with a planned recruitment time of 12 months and a 4-year follow-up. The study population will comprise a longitudinal cohort study, collecting data on patients with prevalent and incident pulmonary hypertension. Will be included patients of age >2 years and diagnosis of pulmonary hypertension by right heart catheterization within Group 1 and Group 4 of the World Health Organization classification. The structure, data collection and data analysis will be based on quality current recommendations for registries. The protocol has been approved by institutional ethics committees in all participant centers. All patients will sign an informed consent form. Currently in Mexico, there is a need of observational registries that include patients with treatment in the everyday clinical practice so the data could be validated and additional information could be obtained versus the one from the clinical trials. In this way, REMEHIP emerges as a link among randomized clinical trials developed by experts and previous Mexican experience. Copyright © 2016 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

  9. Clinical Case Registries: Simultaneous Local and National Disease Registries for Population Quality Management

    Science.gov (United States)

    Backus, Lisa I.; Gavrilov, Sergey; Loomis, Timothy P.; Halloran, James P.; Phillips, Barbara R.; Belperio, Pamela S.; Mole, Larry A.

    2009-01-01

    The Department of Veterans Affairs (VA) has a system-wide, patient-centric electronic medical record system (EMR) within which the authors developed the Clinical Case Registries (CCR) to support population-centric delivery and evaluation of VA medical care. To date, the authors have applied the CCR to populations with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Local components use diagnosis codes and laboratory test results to identify patients who may have HIV or HCV and support queries on local care delivery with customizable reports. For each patient in a local registry, key EMR data are transferred via HL7 messaging to a single national registry. From 128 local registry systems, over 60,000 and 320,000 veterans in VA care have been identified as having HIV and HCV, respectively, and entered in the national database. Local and national reports covering demographics, resource usage, quality of care metrics and medication safety issues have been generated. PMID:19717794

  10. The Italian Registry of Antiphospholipid Antibodies.

    Science.gov (United States)

    Finazzi, G

    1997-01-01

    The clinical importance of antiphospholipid antibodies (APA) derives from their association with a syndrome of venous and arterial thrombosis, recurrent fetal loss and thrombocytopenia known as the antiphospholipid syndrome (APS). The Italian Registry of Antiphospholipid Antibodies was set up in 1989 for the purpose of collecting a large number of patients with lupus anticoagulant (LA) or anticardiolipin antibodies (ACA) for clinical studies in order to obtain more information on the clinical features of APS. The Italian Registry has completed two clinical studies and proposed an international trial on the treatment of APS patients. These activities of the Registry are reviewed herein. Additional information has been obtained from pertinent articles and abstracts published in journals covered by the Science Citation Index and Medline. The first study of the Registry was a retrospective analysis of enrolled patients which showed that: a) the prevalence of thrombosis and thrombocytopenia was similar in cases with idiopathic APA or APA secondary to systemic lupus erythematosus, and b) the rate of thrombosis was significantly reduced in patients with severe thrombocytopenia but not in those with only a mild reduction of the platelet count. The second study was a prospective survey of the natural history of the disease, showing that a) previous thrombosis and ACA titer > 40 units were independent predictors of subsequent vascular complications; b) a history of miscarriage or thrombosis is significantly associated with adverse pregnancy outcome; c) hematological malignancies can develop during follow-up and patients with APA should be considered at increased risk of developing NHL. Thus the possibility of a hematologic neoplastic disease should be borne in mind in the initial evaluation and during the follow-up of these patients. The latest initiative of the Registry was the proposal of an international, randomized clinical trial (WAPS study) aimed at assessing the

  11. EPA Facility Registry Service (FRS): ER_STATE_ID

    Data.gov (United States)

    U.S. Environmental Protection Agency — To improve public health and the environment, the United States Environmental Protection Agency (USEPA) collects information about facilities, sites, or places...

  12. EPA Facility Registry Service (FRS): ER_WTP

    Data.gov (United States)

    U.S. Environmental Protection Agency — To improve public health and the environment, the United States Environmental Protection Agency (USEPA) collects information about facilities, sites, or places...

  13. EPA Facility Registry Service (FRS): ER_SIC

    Data.gov (United States)

    U.S. Environmental Protection Agency — To improve public health and the environment, the United States Environmental Protection Agency (USEPA) collects information about facilities, sites, or places...

  14. EPA Facility Registry Service (FRS): NPDES Sub Facilities

    Data.gov (United States)

    U.S. Environmental Protection Agency — As authorized by the Clean Water Act, the National Pollutant Discharge Elimination System (NPDES), permit program controls water pollution by regulating point...

  15. EPA Facility Registry Service (FRS): ER_NAICS

    Data.gov (United States)

    U.S. Environmental Protection Agency — To improve public health and the environment, the United States Environmental Protection Agency (USEPA) collects information about facilities, sites, or places...

  16. EPA Facility Registry Service (FRS): ER_CONTACTS

    Data.gov (United States)

    U.S. Environmental Protection Agency — To improve public health and the environment, the United States Environmental Protection Agency (USEPA) collects information about facilities, sites, or places...

  17. EPA Facility Registry Service (FRS): AIRS_AFS Sub Facilities

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Air Facility System (AFS) contains compliance and permit data for stationary sources regulated by EPA, state and local air pollution agencies. The sub facility...

  18. Engineering Plant Immunity via CRISPR/Cas13a System

    KAUST Repository

    Aljedaani, Fatimah R.

    2018-01-01

    systems function as an adaptive immune system to provide bacteria with resistance against invading phages and conjugative plasmids. Interestingly, CRISPR/Cas9 system was shown to interfere with eukaryotic DNA viruses and confer resistance against plant DNA

  19. CRISPR/Cas13 as a Tool for RNA Interference

    KAUST Repository

    Ali, Zahir; Mahas, Ahmed; Mahfouz, Magdy M.

    2018-01-01

    Almost all biological processes involve RNA, making it crucial to develop tools for manipulation of the transcriptome. The bacterial CRISPR/Cas13 system was recently rewired to facilitate RNA manipulation in eukaryotes, including plants. We discuss

  20. CRISPR/Cas9-mediated viral interference in plants

    KAUST Repository

    Ali, Zahir; Abulfaraj, Aala A.; Idris, Ali; Ali, Shawkat; Tashkandi, Manal; Mahfouz, Magdy M.

    2015-01-01

    These data establish the efficacy of the CRISPR/Cas9 system for viral interference in plants, thereby extending the utility of this technology and opening the possibility of producing plants resistant to multiple viral infections.

  1. CRISPR-Cas systems: prokaryotes upgrade to adaptive immunity

    Science.gov (United States)

    Barrangou, Rodolphe; Marraffini, Luciano A.

    2014-01-01

    Summary Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), and associated proteins (Cas) comprise the CRISPR-Cas system, which confers adaptive immunity against exogenic elements in many bacteria and most archaea. CRISPR-mediated immunization occurs through the uptake of DNA from invasive genetic elements such as plasmids and viruses, followed by its integration into CRISPR loci. These loci are subsequently transcribed and processed into small interfering RNAs that guide nucleases for specific cleavage of complementary sequences. Conceptually, CRISPR-Cas shares functional features with the mammalian adaptive immune system, while also exhibiting characteristics of Lamarckian evolution. Because immune markers spliced from exogenous agents are integrated iteratively in CRISPR loci, they constitute a genetic record of vaccination events and reflect environmental conditions and changes over time. Cas endonucleases, which can be reprogrammed by small guide RNAs have shown unprecedented potential and flexibility for genome editing, and can be repurposed for numerous DNA targeting applications including transcriptional control. PMID:24766887

  2. Diagnostic ?tiologique du diab?te insipide central: ? propos de 41 cas

    OpenAIRE

    Chaker, Fatma; Chihaoui, Melika; Yazidi, Meriem; Slimane, Hedia

    2016-01-01

    La survenue d'un syndrome polyuro-polydipsiqueavec des urines hypotoniques n?cessite une strat?gie diagnostique rigoureuse. Le but de cette ?tude ?tait d??tudier les modalit?s de diagnostic du diab?te insipide central. A travers une ?tude r?trospective de 41 cas de diab?te insipide central(DIC) collig?s au service d'Endocrinologie ? l'h?pital de la Rabta de Tunis, allant de l'ann?e 1990 ? l'an 2013, nous avons relev? les circonstances de d?couverte du DIC, les anomalies du bilan ant?-hypophys...

  3. Mariage non consommé et vaginisme: à propos de trois cas Clinique

    Science.gov (United States)

    2017-01-01

    Le vaginisme est un problème de couple. Il est source de mariages non consommés, d’infertilité et d’altération de la qualité de la relation sexuelle du couple. Par trois cas cliniques illustratifs rapportés de notre pratique clinique quotidienne et suivis sur deux années en consultation du service de psychiatrie de l’Hôpital Militaire Moulay Ismail de Meknès, nous essayons de clarifier les motifs de rencontre pour vaginisme, ses aspects cliniques et relationnels et ses particularités culturelles. PMID:28819482

  4. Developing the Safety of Atrial Fibrillation Ablation Registry Initiative (SAFARI) as a collaborative pan-stakeholder critical path registry model: a Cardiac Safety Research Consortium "Incubator" Think Tank.

    Science.gov (United States)

    Al-Khatib, Sana M; Calkins, Hugh; Eloff, Benjamin C; Kowey, Peter; Hammill, Stephen C; Ellenbogen, Kenneth A; Marinac-Dabic, Danica; Waldo, Albert L; Brindis, Ralph G; Wilbur, David J; Jackman, Warren M; Yaross, Marcia S; Russo, Andrea M; Prystowsky, Eric; Varosy, Paul D; Gross, Thomas; Pinnow, Ellen; Turakhia, Mintu P; Krucoff, Mitchell W

    2010-10-01

    Although several randomized clinical trials have demonstrated the safety and efficacy of catheter ablation of atrial fibrillation (AF) in experienced centers, the outcomes of this procedure in routine clinical practice and in patients with persistent and long-standing persistent AF remain uncertain. Brisk adoption of this therapy by physicians with diverse training and experience highlights potential concerns regarding the safety and effectiveness of this procedure. Some of these concerns could be addressed by a national registry of AF ablation procedures such as the Safety of Atrial Fibrillation Ablation Registry Initiative that was initially proposed at a Cardiac Safety Research Consortium Think Tank meeting in April 2009. In January 2010, the Cardiac Safety Research Consortium, in collaboration with the Duke Clinical Research Institute, the US Food and Drug Administration, the American College of Cardiology, and the Heart Rhythm Society, held a follow-up meeting of experts in the field to review the construct and progress to date. Other participants included the National Heart, Lung, and Blood Institute; the Centers for Medicare and Medicaid Services; the Agency for Healthcare Research and Quality; the AdvaMed AF working group; and additional industry representatives. This article summarizes the discussions that occurred at the meeting of the state of the Safety of Atrial Fibrillation Ablation Registry Initiative, the identification of a clear pathway for its implementation, and the exploration of solutions to potential issues in the execution of this registry. Copyright © 2010 Mosby, Inc. All rights reserved.

  5. Iranian Joint Registry(Iranian National Hip and Knee Arthroplasty Registry

    Directory of Open Access Journals (Sweden)

    Hamidreza Aslani

    2016-04-01

    Full Text Available Periodic evaluation and monitoring the health and economic outcome of joint replacement surgery is a common and popular process under the territory of joint registries in many countries. In this article we introduce the methodology used for the foundation of the National Iranian Joint Registry (IJR with a joint collaboration of the Social Security Organization (SSO and academic research departments considering the requirements of the Iran’s Ministry of Health and Education.

  6. BioShaDock: a community driven bioinformatics shared Docker-based tools registry [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    François Moreews

    2015-12-01

    Full Text Available Linux container technologies, as represented by Docker, provide an alternative to complex and time-consuming installation processes needed for scientific software. The ease of deployment and the process isolation they enable, as well as the reproducibility they permit across environments and versions, are among the qualities that make them interesting candidates for the construction of bioinformatic infrastructures, at any scale from single workstations to high throughput computing architectures. The Docker Hub is a public registry which can be used to distribute bioinformatic software as Docker images. However, its lack of curation and its genericity make it difficult for a bioinformatics user to find the most appropriate images needed. BioShaDock is a bioinformatics-focused Docker registry, which provides a local and fully controlled environment to build and publish bioinformatic software as portable Docker images. It provides a number of improvements over the base Docker registry on authentication and permissions management, that enable its integration in existing bioinformatic infrastructures such as computing platforms. The metadata associated with the registered images are domain-centric, including for instance concepts defined in the EDAM ontology, a shared and structured vocabulary of commonly used terms in bioinformatics. The registry also includes user defined tags to facilitate its discovery, as well as a link to the tool description in the ELIXIR registry if it already exists. If it does not, the BioShaDock registry will synchronize with the registry to create a new description in the Elixir registry, based on the BioShaDock entry metadata. This link will help users get more information on the tool such as its EDAM operations, input and output types. This allows integration with the ELIXIR Tools and Data Services Registry, thus providing the appropriate visibility of such images to the bioinformatics community.

  7. Cas4-Dependent Prespacer Processing Ensures High-Fidelity Programming of CRISPR Arrays.

    Science.gov (United States)

    Lee, Hayun; Zhou, Yi; Taylor, David W; Sashital, Dipali G

    2018-04-05

    CRISPR-Cas immune systems integrate short segments of foreign DNA as spacers into the host CRISPR locus to provide molecular memory of infection. Cas4 proteins are widespread in CRISPR-Cas systems and are thought to participate in spacer acquisition, although their exact function remains unknown. Here we show that Bacillus halodurans type I-C Cas4 is required for efficient prespacer processing prior to Cas1-Cas2-mediated integration. Cas4 interacts tightly with the Cas1 integrase, forming a heterohexameric complex containing two Cas1 dimers and two Cas4 subunits. In the presence of Cas1 and Cas2, Cas4 processes double-stranded substrates with long 3' overhangs through site-specific endonucleolytic cleavage. Cas4 recognizes PAM sequences within the prespacer and prevents integration of unprocessed prespacers, ensuring that only functional spacers will be integrated into the CRISPR array. Our results reveal the critical role of Cas4 in maintaining fidelity during CRISPR adaptation, providing a structural and mechanistic model for prespacer processing and integration. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Nordic registry-based cohort studies: Possibilities and pitfalls when combining Nordic registry data.

    Science.gov (United States)

    Maret-Ouda, John; Tao, Wenjing; Wahlin, Karl; Lagergren, Jesper

    2017-07-01

    All five Nordic countries (Denmark, Finland, Iceland, Norway and Sweden) have nationwide registries with similar data structure and validity, as well as personal identity numbers enabling linkage between registries. These resources provide opportunities for medical research that is based on large registry-based cohort studies with long and complete follow-up. This review describes practical aspects, opportunities and challenges encountered when setting up all-Nordic registry-based cohort studies. Relevant articles describing registries often used for medical research in the Nordic countries were retrieved. Further, our experiences of conducting this type of study, including planning, acquiring permissions, data retrieval and data cleaning and handling, and the possibilities and challenges we have encountered are described. Combining data from the Nordic countries makes it possible to create large and powerful cohorts. The main challenges include obtaining all permissions within each country, usually in the local language, and retrieving the data. These challenges emphasise the importance of having experienced collaborators within each country. Following the acquisition of data, data management requires the understanding of the differences between the variables to be used in the various countries. A concern is the long time required between initiation and completion. Nationwide Nordic registries can be combined into cohorts with high validity and statistical power, but the considerable expertise, workload and time required to complete such cohorts should not be underestimated.

  9. CRISPR/Cas9: Transcending the Reality of Genome Editing.

    Science.gov (United States)

    Chira, Sergiu; Gulei, Diana; Hajitou, Amin; Zimta, Alina-Andreea; Cordelier, Pierre; Berindan-Neagoe, Ioana

    2017-06-16

    With the expansion of the microbiology field of research, a new genome editing tool arises from the biology of bacteria that holds the promise of achieving precise modifications in the genome with a simplicity and versatility that surpasses previous genome editing methods. This new technique, commonly named CRISPR/Cas9, led to a rapid expansion of the biomedical field; more specifically, cancer characterization and modeling have benefitted greatly from the genome editing capabilities of CRISPR/Cas9. In this paper, we briefly summarize recent improvements in CRISPR/Cas9 design meant to overcome the limitations that have arisen from the nuclease activity of Cas9 and the influence of this technology in cancer research. In addition, we present challenges that might impede the clinical applicability of CRISPR/Cas9 for cancer therapy and highlight future directions for designing CRISPR/Cas9 delivery systems that might prove useful for cancer therapeutics. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  10. Applications of CRISPR/Cas System to Bacterial Metabolic Engineering

    Directory of Open Access Journals (Sweden)

    Suhyung Cho

    2018-04-01

    Full Text Available The clustered regularly interspaced short palindromic repeats/CRISPR-associated (CRISPR/Cas adaptive immune system has been extensively used for gene editing, including gene deletion, insertion, and replacement in bacterial and eukaryotic cells owing to its simple, rapid, and efficient activities in unprecedented resolution. Furthermore, the CRISPR interference (CRISPRi system including deactivated Cas9 (dCas9 with inactivated endonuclease activity has been further investigated for regulation of the target gene transiently or constitutively, avoiding cell death by disruption of genome. This review discusses the applications of CRISPR/Cas for genome editing in various bacterial systems and their applications. In particular, CRISPR technology has been used for the production of metabolites of high industrial significance, including biochemical, biofuel, and pharmaceutical products/precursors in bacteria. Here, we focus on methods to increase the productivity and yield/titer scan by controlling metabolic flux through individual or combinatorial use of CRISPR/Cas and CRISPRi systems with introduction of synthetic pathway in industrially common bacteria including Escherichia coli. Further, we discuss additional useful applications of the CRISPR/Cas system, including its use in functional genomics.

  11. Editing plants for virus resistance using CRISPR-Cas.

    Science.gov (United States)

    Green, J C; Hu, J S

    This minireview summarizes recent advancements using the clustered regularly interspaced palindromic repeats-associated nuclease systems (CRISPR-Cas) derived from prokaryotes to breed plants resistant to DNA and RNA viruses. The CRISPR-Cas system represents a powerful tool able to edit and insert novel traits into plants precisely at chosen loci offering enormous advantages to classical breeding. Approaches to engineering plant virus resistance in both transgenic and non-transgenic plants are discussed. Iterations of the CRISPR-Cas system, FnCas9 and C2c2 capable of editing RNA in eukaryotic cells offer a particular advantage for providing resistance to RNA viruses which represent the great majority of known plant viruses. Scientists have obtained conflicting results using gene silencing technology to produce transgenic plants resistant to geminiviruses. CRISPR-Cas systems engineered in plants to target geminiviruses have consistently reduced virus accumulation providing increased resistance to virus infection. CRISPR-Cas may provide novel and reliable approaches to control geminiviruses and other ssDNA viruses such as Banana bunchy top virus (BBTV).

  12. Efficient CRISPR/Cas9-based gene knockout in watermelon.

    Science.gov (United States)

    Tian, Shouwei; Jiang, Linjian; Gao, Qiang; Zhang, Jie; Zong, Mei; Zhang, Haiying; Ren, Yi; Guo, Shaogui; Gong, Guoyi; Liu, Fan; Xu, Yong

    2017-03-01

    CRISPR/Cas9 system can precisely edit genomic sequence and effectively create knockout mutations in T0 generation watermelon plants. Genome editing offers great advantage to reveal gene function and generate agronomically important mutations to crops. Recently, RNA-guided genome editing system using the type II clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (Cas9) has been applied to several plant species, achieving successful targeted mutagenesis. Here, we report the genome of watermelon, an important fruit crop, can also be precisely edited by CRISPR/Cas9 system. ClPDS, phytoene desaturase in watermelon, was selected as the target gene because its mutant bears evident albino phenotype. CRISPR/Cas9 system performed genome editing, such as insertions or deletions at the expected position, in transfected watermelon protoplast cells. More importantly, all transgenic watermelon plants harbored ClPDS mutations and showed clear or mosaic albino phenotype, indicating that CRISPR/Cas9 system has technically 100% of genome editing efficiency in transgenic watermelon lines. Furthermore, there were very likely no off-target mutations, indicated by examining regions that were highly homologous to sgRNA sequences. Our results show that CRISPR/Cas9 system is a powerful tool to effectively create knockout mutations in watermelon.

  13. 14 CFR 47.19 - FAA Aircraft Registry.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false FAA Aircraft Registry. 47.19 Section 47.19... REGISTRATION General § 47.19 FAA Aircraft Registry. Each application, request, notification, or other communication sent to the FAA under this Part must be mailed to the FAA Aircraft Registry, Department of...

  14. 14 CFR 49.11 - FAA Aircraft Registry.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false FAA Aircraft Registry. 49.11 Section 49.11... AIRCRAFT TITLES AND SECURITY DOCUMENTS General § 49.11 FAA Aircraft Registry. To be eligible for recording, a conveyance must be mailed to the FAA Aircraft Registry, Department of Transportation, Post Office...

  15. A review of national shoulder and elbow joint replacement registries

    DEFF Research Database (Denmark)

    Rasmussen, Jeppe V; Olsen, Bo S; Fevang, Bjørg-Tilde S

    2012-01-01

    The aim was to review the funding, organization, data handling, outcome measurements, and findings from existing national shoulder and elbow joint replacement registries; to consider the possibility of pooling data between registries; and to consider wether a pan european registry might be feasible....

  16. Mutations in Cas9 Enhance the Rate of Acquisition of Viral Spacer Sequences during the CRISPR-Cas Immune Response.

    Science.gov (United States)

    Heler, Robert; Wright, Addison V; Vucelja, Marija; Bikard, David; Doudna, Jennifer A; Marraffini, Luciano A

    2017-01-05

    CRISPR loci and their associated (Cas) proteins encode a prokaryotic immune system that protects against viruses and plasmids. Upon infection, a low fraction of cells acquire short DNA sequences from the invader. These sequences (spacers) are integrated in between the repeats of the CRISPR locus and immunize the host against the matching invader. Spacers specify the targets of the CRISPR immune response through transcription into short RNA guides that direct Cas nucleases to the invading DNA molecules. Here we performed random mutagenesis of the RNA-guided Cas9 nuclease to look for variants that provide enhanced immunity against viral infection. We identified a mutation, I473F, that increases the rate of spacer acquisition by more than two orders of magnitude. Our results highlight the role of Cas9 during CRISPR immunization and provide a useful tool to study this rare process and develop it as a biotechnological application. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Examination of CRISPR/Cas9 design tools and the effect of target site accessibility on Cas9 activity.

    Science.gov (United States)

    Lee, Ciaran M; Davis, Timothy H; Bao, Gang

    2018-04-01

    What is the topic of this review? In this review, we analyse the performance of recently described tools for CRISPR/Cas9 guide RNA design, in particular, design tools that predict CRISPR/Cas9 activity. What advances does it highlight? Recently, many tools designed to predict CRISPR/Cas9 activity have been reported. However, the majority of these tools lack experimental validation. Our analyses indicate that these tools have poor predictive power. Our preliminary results suggest that target site accessibility should be considered in order to develop better guide RNA design tools with improved predictive power. The recent adaptation of the clustered regulatory interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system for targeted genome engineering has led to its widespread application in many fields worldwide. In order to gain a better understanding of the design rules of CRISPR/Cas9 systems, several groups have carried out large library-based screens leading to some insight into sequence preferences among highly active target sites. To facilitate CRISPR/Cas9 design, these studies have spawned a plethora of guide RNA (gRNA) design tools with algorithms based solely on direct or indirect sequence features. Here, we demonstrate that the predictive power of these tools is poor, suggesting that sequence features alone cannot accurately inform the cutting efficiency of a particular CRISPR/Cas9 gRNA design. Furthermore, we demonstrate that DNA target site accessibility influences the activity of CRISPR/Cas9. With further optimization, we hypothesize that it will be possible to increase the predictive power of gRNA design tools by including both sequence and target site accessibility metrics. © 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.

  18. Clinical trial registries: a practical guide for sponsors and researchers of medicinal products

    National Research Council Canada - National Science Library

    Foote, MaryAnn

    2006-01-01

    ... Industry perspective on public clinical trial registries and results databases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ...

  19. Using the IR as a Research Data Registry

    KAUST Repository

    Grenz, Daryl M.

    2018-05-01

    As data and software become increasingly common research outputs, universities have an opportunity to expand their existing efforts to record affiliated publications so that they also capture information about research data releases. At KAUST we have taken several steps to put our repository on a path towards becoming a reliable registry for information about the existence and location of research data released by affiliated researchers. These included developing a process to retrospectively retrieve and register information about datasets with machine-readable relationships to publications already in the repository, and updates to our active publications tracking procedures so that data availability statements are retrieved at the time of harvesting and checked for references to research data. The presentation will conclude by discussing how these efforts help put the repository in a position to provide expanded services in support of improved research data management, including access to and preservation of research data not explicitly linked to a formal publication.

  20. The Spanish National Dose Registry and Spanish radiation passbooks

    International Nuclear Information System (INIS)

    Hernandez, A.; Martin, A.; Villanueva, I.; Amor, I.; Butragueno, J.L.

    2001-01-01

    The Spanish National Dose Registry (BDN) is the Nuclear Safety Council's (CSN) national database of occupational exposure to radiation. Each month BDN receives records of individual external doses from approved dosimetry services. The dose records include information regarding the occupational activities of exposed workers. The dose information and the statistical analysis prepared by the BDN are a useful tool for effective operational protection of occupationally exposed workers and a support for the CSN in the development and application of the ALARA principle. The Spanish radiation passbook was introduced in 1990 and since then CSN, as regulatory authority, has required that all outside workers entering controlled areas should have radiation passbooks. Nowadays, CSN has implemented improvements in the Spanish radiation Passbooks, taking into account previous experience and Directive 96/29/EURATOM. (author)

  1. Towards a national trauma registry for the United Arab Emirates

    Directory of Open Access Journals (Sweden)

    Barka Ezedin

    2010-07-01

    Full Text Available Abstract Background Trauma is a major health problem in the United Arab Emirates (UAE as well as worldwide. Trauma registries provide large longitudinal databases for analysis and policy improvement. We aim in this paper to report on the development and evolution of a national trauma registry using a staged approach by developing a single-center registry, a two-center registry, and then a multi-center registry. The three registries were established by developing suitable data collection forms, databases, and interfaces to these databases. The first two registries collected data for a finite period of time and the third is underway. The steps taken to establish these registries depend on whether the registry is intended as a single-center or multi-center registry. Findings Several issues arose and were resolved during the development of these registries such as the relational design of the database, whether to use a standalone database management system or a web-based system, and the usability and security of the system. The inclusion of preventive medicine data elements is important in a trauma registry and the focus on road traffic collision data elements is essential in a country such as the UAE. The first two registries provided valuable data which has been analyzed and published. Conclusions The main factors leading to the successful establishment of a multi-center trauma registry are the development of a concise data entry form, development of a user-friendly secure web-based database system, the availability of a computer and Internet connection in each data collection center, funded data entry personnel well trained in extracting medical data from the medical record and entering it into the computer, and experienced personnel in trauma injuries and data analysis to continuously maintain and analyze the registry.

  2. Cohort Profile : The National Academy of Sciences-National Research Council Twin Registry (NAS-NRC Twin Registry)

    NARCIS (Netherlands)

    Gatz, Margaret; Harris, Jennifer R.; Kaprio, Jaakko; McGue, Matt; Smith, Nicholas L.; Snieder, Harold; Spiro, Avron; Butler, David A.

    The National Academy of Sciences-National Research Council Twin Registry (NAS-NRC Twin Registry) is a comprehensive registry of White male twin pairs born in the USA between 1917 and 1927, both of the twins having served in the military. The purpose was medical research and ultimately improved

  3. A Cas9 transgenic Plasmodium yoelii parasite for efficient gene editing.

    Science.gov (United States)

    Qian, Pengge; Wang, Xu; Yang, Zhenke; Li, Zhenkui; Gao, Han; Su, Xin-Zhuan; Cui, Huiting; Yuan, Jing

    2018-06-01

    The RNA-guided endonuclease Cas9 has applied as an efficient gene-editing method in malaria parasite Plasmodium. However, the size (4.2 kb) of the commonly used Cas9 from Streptococcus pyogenes (SpCas9) limits its utility for genome editing in the parasites only introduced with cas9 plasmid. To establish the endogenous and constitutive expression of Cas9 protein in the rodent malaria parasite P. yoelii, we replaced the coding region of an endogenous gene sera1 with the intact SpCas9 coding sequence using the CRISPR/Cas9-mediated genome editing method, generating the cas9-knockin parasite (PyCas9ki) of the rodent malaria parasite P. yoelii. The resulted PyCas9ki parasite displays normal progression during the whole life cycle and possesses the Cas9 protein expression in asexual blood stage. By introducing the plasmid (pYCs) containing only sgRNA and homologous template elements, we successfully achieved both deletion and tagging modifications for different endogenous genes in the genome of PyCas9ki parasite. This cas9-knockin PyCas9ki parasite provides a new platform facilitating gene functions study in the rodent malaria parasite P. yoelii. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Cas9 in Genetically Modified Food Is Unlikely to Cause Food Allergy.

    Science.gov (United States)

    Nakajima, Osamu; Nishimaki-Mogami, Tomoko; Kondo, Kazunari

    2016-01-01

    Genome editing has undergone rapid development during the last three years. It is anticipated that genetically modified organisms (GMOs) for food purposes will be widely produced using the clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR)/Cas9 system in the near future. However, the Cas9 gene may then enter the genomes of GMOs for food if the breeding process is not strictly managed, which could lead to the Cas9 protein or associated peptides being produced within these organisms. A variety of peptides could theoretically be produced from the Cas9 gene by using open reading frames different from that of Cas9 in the GMOs. In this study, Cas9 and the peptides potentially encoded by Cas9 genes were studied regarding their immunogenicity, in terms of the digestibility of Cas9 and the homology of the peptides to food allergens. First, the digestibility and thermal stability of Cas9 were studied. Digestibility was tested with natural or heat-denatured Cas9 in simulated gastric fluid in vitro. The two types of Cas9 were digested rapidly. Cas9 was also gradually degraded during heat treatment. Second, the peptides potentially encoded by Cas9 genes were examined for their homology to food allergens. Specifically, an 8-mer exact match search and a sliding 80-mer window search were performed using allergen databases. One of the peptides was found to have homology with a food allergen.

  5. Agile Model Driven Development of Electronic Health Record-Based Specialty Population Registries

    Science.gov (United States)

    Kannan, Vaishnavi; Fish, Jason C.; Willett, DuWayne L.

    2018-01-01

    The transformation of the American healthcare payment system from fee-for-service to value-based care increasingly makes it valuable to develop patient registries for specialized populations, to better assess healthcare quality and costs. Recent widespread adoption of Electronic Health Records (EHRs) in the U.S. now makes possible construction of EHR-based specialty registry data collection tools and reports, previously unfeasible using manual chart abstraction. But the complexities of specialty registry EHR tools and measures, along with the variety of stakeholders involved, can result in misunderstood requirements and frequent product change requests, as users first experience the tools in their actual clinical workflows. Such requirements churn could easily stall progress in specialty registry rollout. Modeling a system’s requirements and solution design can be a powerful way to remove ambiguities, facilitate shared understanding, and help evolve a design to meet newly-discovered needs. “Agile Modeling” retains these values while avoiding excessive unused up-front modeling in favor of iterative incremental modeling. Using Agile Modeling principles and practices, in calendar year 2015 one institution developed 58 EHR-based specialty registries, with 111 new data collection tools, supporting 134 clinical process and outcome measures, and enrolling over 16,000 patients. The subset of UML and non-UML models found most consistently useful in designing, building, and iteratively evolving EHR-based specialty registries included User Stories, Domain Models, Use Case Diagrams, Decision Trees, Graphical User Interface Storyboards, Use Case text descriptions, and Solution Class Diagrams. PMID:29750222

  6. Registry of Mineral and Petroleum Titles

    Energy Technology Data Exchange (ETDEWEB)

    Maclellan, I. M.; Kaizer, J. L.; McCulloch, P. D.; Ratcliffe, R.; Wenning, A. S. [Nova Scotia Dept. of Natural Resources, Halifax, NS (Canada)

    2000-07-01

    Activities of the Nova Scotia Registry of Mineral and Petroleum Titles are described, including statistical information about staking and mining activity in the province during 1999. In terms of activities, the Registry receives applications and issues licenses and leases for mineral and petroleum rights, receives statements of exploration expenditures and assessment reports that pertain to renewal of licenses and leases, maintains maps showing the disposition of lands under license or lease, and maintains a system of prospector registration. In addition, the Registry processes applications for underground gas storage rights and treasure trove rights and maintains a database of information concerning production and employment in Nova Scotia mines and quarries. At the end 1999 there were 230,660 hectares under exploration licence. Exploration expenditures, including engineering, economic and feasibility studies during 1999 totalled $4.2 million, mostly by junior mining companies searching for industrial mineral commodities. Mining activity during 1999 generated revenues of $340 million. Coal production dropped by 25 per cent, due mainly to the closure of the Phalen Mine. Gypsum production was up to 7.9 million tonnes; shipments of cement, barite and clay products also increased during 1999; salt production remained unchanged from 1998 with 842,000 tonnes. Production of construction aggregates totalled 10.6 million tonnes, down slightly from the year before. Mineral industry employment was roughly 2,500 persons, down by 24 per cent from 1998 levels, due primarily to the closure of the Phalen Mine.

  7. Comparative analysis of CRISPR-Cas systems in Klebsiella genomes.

    Science.gov (United States)

    Shen, Juntao; Lv, Li; Wang, Xudong; Xiu, Zhilong; Chen, Guoqiang

    2017-04-01

    Prokaryotic CRISPR-Cas system provides adaptive immunity against invasive genetic elements. Bacteria of the genus Klebsiella are important nosocomial opportunistic pathogens. However, information of CRISPR-Cas system in Klebsiella remains largely unknown. Here, we analyzed the CRISPR-Cas systems of 68 complete genomes of Klebsiella representing four species. All the elements for CRISPR-Cas system (cas genes, repeats, leader sequences, and PAMs) were characterized. Besides the typical Type I-E and I-F CRISPR-Cas systems, a new Subtype I system located in the ABC transport system-glyoxalase region was found. The conservation of the new subtype CRISPR system between different species showed new evidence for CRISPR horizontal transfer. CRISPR polymorphism was strongly correlated both with species and multilocus sequence types. Some results indicated the function of adaptive immunity: most spacers (112 of 124) matched to prophages and plasmids and no matching housekeeping genes; new spacer acquisition was observed within the same sequence type (ST) and same clonal complex; the identical spacers were observed only in the ancient position (far from the leader) between different STs and clonal complexes. Interestingly, a high ratio of self-targeting spacers (7.5%, 31 of 416) was found in CRISPR-bearing Klebsiella pneumoniae (61%, 11 of 18). In some strains, there even were multiple full matching self-targeting spacers. Some self-targeting spacers were conserved even between different STs. These results indicated that some unknown mechanisms existed to compromise the function of self-targets of CRISPR-Cas systems in K. pneumoniae. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Les tumeurs malignes naso-sinusiennes: à propos de 32 cas et revues de la littérature

    Science.gov (United States)

    Darouassi, Youssef; Touati, Mohamed Mliha; Chihani, Mehdi; El Alami, Jihane; Bouaity, Brahim; Ammar, Haddou

    2015-01-01

    Sous l’appellation tumeurs malignes naso-sinusiennes est regroupé un vaste éventail de tumeurs, aux histologies et localisations variées, mais aux tableaux cliniques souvent similaires. Le diagnostic de ces tumeurs est difficile, nécessitant une approche multidisciplinaire, à savoir oto-rhino-laryngologique, radiologique et anatomopathologique. Notre étude rétrospective concerne 32 cas de tumeurs malignes naso-sinusiennes, colligées au service d’ORL de l’hôpital militaire Avicenne de Marrakech, entre Janvier 2004 et Décembre 2014. L’analyse des données a noté que la fréquence des tumeurs épithéliales (75% des cas) était supérieure à celle des tumeurs non épithéliales (25% des cas), avec en tête de file l’adénocarcinome de l’ethmoïde (31,25%) et le carcinome épidermoïde du sinus maxillaire (18,75%). Ces tumeurs surviennent le plus souvent chez le sujet âgé avec une moyenne d’âge de 52 ans et une répartition équitable entre les deux sexes. Le délai de consultation moyen était de 12 mois avec une symptomatologie dominée par un syndrome nasosinusien (71,8%), associé dans certains cas à des signes ophtalmologiques (12,5%) ou neurologiques (15,6%). Tous nos patients ont bénéficié d’un examen clinique notamment endoscopique, d’une exploration radiologique des tumeurs et de leurs extensions, et d’une confirmation diagnostique par un examen anatomopathologique. Le traitement a consisté en une exérèse chirurgicale de la tumeur dès que cela était possible, soit dans 81,3% des cas (26 patients), généralement complété par un traitement adjuvant radio-chimiothérapique (77%). Le suivi à un an de nos patients a permis de noter une bonne évolution pour 08 d’entre eux (25%), une récidive dans 6 cas (18,75%), le décès de neuf patients (28,1%), et l’absence d’information concernant les autres cas (28,1%). PMID:26985260

  9. Registry Assessment of Peripheral Interventional Devices (RAPID): Registry assessment of peripheral interventional devices core data elements.

    Science.gov (United States)

    Jones, W Schuyler; Krucoff, Mitchell W; Morales, Pablo; Wilgus, Rebecca W; Heath, Anne H; Williams, Mary F; Tcheng, James E; Marinac-Dabic, J Danica; Malone, Misti L; Reed, Terrie L; Fukaya, Rie; Lookstein, Robert A; Handa, Nobuhiro; Aronow, Herbert D; Bertges, Daniel J; Jaff, Michael R; Tsai, Thomas T; Smale, Joshua A; Zaugg, Margo J; Thatcher, Robert J; Cronenwett, Jack L

    2018-02-01

    The current state of evaluating patients with peripheral artery disease and more specifically of evaluating medical devices used for peripheral vascular intervention (PVI) remains challenging because of the heterogeneity of the disease process, the multiple physician specialties that perform PVI, the multitude of devices available to treat peripheral artery disease, and the lack of consensus about the best treatment approaches. Because PVI core data elements are not standardized across clinical care, clinical trials, and registries, aggregation of data across different data sources and physician specialties is currently not feasible. Under the auspices of the U.S. Food and Drug Administration's Medical Device Epidemiology Network initiative-and its PASSION (Predictable and Sustainable Implementation of the National Registries) program, in conjunction with other efforts to align clinical data standards-the Registry Assessment of Peripheral Interventional Devices (RAPID) workgroup was convened. RAPID is a collaborative, multidisciplinary effort to develop a consensus lexicon and to promote interoperability across clinical care, clinical trials, and national and international registries of PVI. The current manuscript presents the initial work from RAPID to standardize clinical data elements and definitions, to establish a framework within electronic health records and health information technology procedural reporting systems, and to implement an informatics-based approach to promote the conduct of pragmatic clinical trials and registry efforts in PVI. Ultimately, we hope this work will facilitate and improve device evaluation and surveillance for patients, clinicians, health outcomes researchers, industry, policymakers, and regulators. Copyright © 2017 Society for Vascular Surgery. All rights reserved.

  10. 77 FR 58141 - Public Buildings Service; Information Collection; Art-in-Architecture Program National Artist...

    Science.gov (United States)

    2012-09-19

    ... Buildings Service; Information Collection; Art-in- Architecture Program National Artist Registry (GSA Form... Information Collection 3090- 0274, Art-in-Architecture Program National Artist Registry (GSA Form 7437), by... corresponds with ``Information Collection 3090-0274, Art-in- Architecture Program National Artist Registry...

  11. Complementary Information Derived from CRISPR Cas9 Mediated Gene Deletion and Suppression. | Office of Cancer Genomics

    Science.gov (United States)

    CRISPR-Cas9 provides the means to perform genome editing and facilitates loss-of-function screens. However, we and others demonstrated that expression of the Cas9 endonuclease induces a gene-independent response that correlates with the number of target sequences in the genome. An alternative approach to suppressing gene expression is to block transcription using a catalytically inactive Cas9 (dCas9). Here we directly compare genome editing by CRISPR-Cas9 (cutting, CRISPRc) and gene suppression using KRAB-dCas9 (CRISPRi) in loss-of-function screens to identify cell essential genes.

  12. Crystal Structure of the Minimal Cas9 from Campylobacter jejuni Reveals the Molecular Diversity in the CRISPR-Cas9 Systems.

    Science.gov (United States)

    Yamada, Mari; Watanabe, Yuto; Gootenberg, Jonathan S; Hirano, Hisato; Ran, F Ann; Nakane, Takanori; Ishitani, Ryuichiro; Zhang, Feng; Nishimasu, Hiroshi; Nureki, Osamu

    2017-03-16

    The RNA-guided endonuclease Cas9 generates a double-strand break at DNA target sites complementary to the guide RNA and has been harnessed for the development of a variety of new technologies, such as genome editing. Here, we report the crystal structures of Campylobacter jejuni Cas9 (CjCas9), one of the smallest Cas9 orthologs, in complex with an sgRNA and its target DNA. The structures provided insights into a minimal Cas9 scaffold and revealed the remarkable mechanistic diversity of the CRISPR-Cas9 systems. The CjCas9 guide RNA contains a triple-helix structure, which is distinct from known RNA triple helices, thereby expanding the natural repertoire of RNA triple helices. Furthermore, unlike the other Cas9 orthologs, CjCas9 contacts the nucleotide sequences in both the target and non-target DNA strands and recognizes the 5'-NNNVRYM-3' as the protospacer-adjacent motif. Collectively, these findings improve our mechanistic understanding of the CRISPR-Cas9 systems and may facilitate Cas9 engineering. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Versatile Cas9-Driven Subpopulation Selection Toolbox for Lactococcus lactis.

    Science.gov (United States)

    van der Els, Simon; James, Jennelle K; Kleerebezem, Michiel; Bron, Peter A

    2018-04-15

    CRISPR-Cas9 technology has been exploited for the removal or replacement of genetic elements in a wide range of prokaryotes and eukaryotes. Here, we describe the extension of the Cas9 application toolbox to the industrially important dairy species Lactococcus lactis The Cas9 expression vector pLABTarget, encoding the Streptocccus pyogenes Cas9 under the control of a constitutive promoter, was constructed, allowing plug and play introduction of short guide RNA (sgRNA) sequences to target specific genetic loci. Introduction of a pepN -targeting derivative of pLABTarget into L. lactis strain MG1363 led to a strong reduction in the number of transformants obtained, which did not occur in a pepN deletion derivative of the same strain, demonstrating the specificity and lethality of the Cas9-mediated double-strand breaks in the lactococcal chromosome. Moreover, the same pLABTarget derivative allowed the selection of a pepN deletion subpopulation from its corresponding single-crossover plasmid integrant precursor, accelerating the construction and selection of gene-specific deletion derivatives in L. lactis Finally, pLABTarget, which contained sgRNAs designed to target mobile genetic elements, allowed the effective curing of plasmids, prophages, and integrative conjugative elements (ICEs). These results establish that pLABTarget enables the effective exploitation of Cas9 targeting in L. lactis , while the broad-host-range vector used suggests that this toolbox could readily be expanded to other Gram-positive bacteria. IMPORTANCE Mobile genetic elements in Lactococcus lactis and other lactic acid bacteria (LAB) play an important role in dairy fermentation, having both positive and detrimental effects during the production of fermented dairy products. The pLABTarget vector offers an efficient cloning platform for Cas9 application in lactic acid bacteria. Targeting Cas9 toward mobile genetic elements enabled their effective curing, which is of particular interest in the

  14. Tuning CRISPR-Cas9 Gene Drives in Saccharomyces cerevisiae

    Science.gov (United States)

    Roggenkamp, Emily; Giersch, Rachael M.; Schrock, Madison N.; Turnquist, Emily; Halloran, Megan; Finnigan, Gregory C.

    2018-01-01

    Control of biological populations is an ongoing challenge in many fields, including agriculture, biodiversity, ecological preservation, pest control, and the spread of disease. In some cases, such as insects that harbor human pathogens (e.g., malaria), elimination or reduction of a small number of species would have a dramatic impact across the globe. Given the recent discovery and development of the CRISPR-Cas9 gene editing technology, a unique arrangement of this system, a nuclease-based “gene drive,” allows for the super-Mendelian spread and forced propagation of a genetic element through a population. Recent studies have demonstrated the ability of a gene drive to rapidly spread within and nearly eliminate insect populations in a laboratory setting. While there are still ongoing technical challenges to design of a more optimal gene drive to be used in wild populations, there are still serious ecological and ethical concerns surrounding the nature of this powerful biological agent. Here, we use budding yeast as a safe and fully contained model system to explore mechanisms that might allow for programmed regulation of gene drive activity. We describe four conserved features of all CRISPR-based drives and demonstrate the ability of each drive component—Cas9 protein level, sgRNA identity, Cas9 nucleocytoplasmic shuttling, and novel Cas9-Cas9 tandem fusions—to modulate drive activity within a population. PMID:29348295

  15. Utilizing a diabetic registry to manage diabetes in a low-income Asian American population.

    Science.gov (United States)

    Seto, Winnie; Turner, Barbara S; Champagne, Mary T; Liu, Lynn

    2012-08-01

    Racial and income disparities persist in diabetes management in America. One third of African and Hispanic Americans with diabetes receive the recommended diabetes services (hemoglobin A1c [A1c] testing, retinal and foot examinations) shown to reduce diabetes complications and mortality, compared to half of whites with diabetes. National data for Asian Americans are limited, but studies suggest that those with language and cultural barriers have difficulty accessing health services. A diabetic registry has been shown to improve process and clinical outcomes in a population with diabetes. This study examined whether a community center that serves primarily low-income Asian American immigrants in Santa Clara County, California, could improve diabetes care and outcomes by implementing a diabetic registry. The registry was built using the Access 2007 software program. A total of 580 patients with diabetes were identified by reviewing charts, the appointment database, and reimbursement records from Medicaid, Medicare, and private insurance companies. Utilizing the registry, medical assistants contacted patients for follow-up appointments, and medical providers checked and tracked the patients' A1c results. Among the 431 patients who returned for treatment, the mean A1c was reduced from 7.27% to 6.97% over 8 months (P<0.001). Although 10.8% of the patients changed from controlled to uncontrolled diabetes post intervention, 32.6% of patients with uncontrolled diabetes converted to controlled diabetes (P<0.001). The diabetes control rate improved from 47% to 59% at the end of the study. This study demonstrated that a diabetic registry is an effective tool to manage an underserved population with diabetes, thereby reducing disparities in diabetes management.

  16. International Consortium of Vascular Registries Consensus Recommendations for Peripheral Revascularisation Registry Data Collection

    DEFF Research Database (Denmark)

    Behrendt, Christian-Alexander; Bertges, Daniel; Eldrup, Nikolaj

    2018-01-01

    intervention; (ix) complications; and (x) follow up. CONCLUSION: A modified Delphi study allowed 25 international vascular registry experts to achieve a consensus recommendation for a minimum core data set and an optimum data set for peripheral arterial revascularisation registries. Continued global...... via internet exchange and face to face discussions. In total, 187 different items from the various registry data forms were identified for potential inclusion in the recommended data set. Ultimately, 79 items were recommended for inclusion in minimum core data sets, including 65 items in the level 1...... data set, and an additional 14 items in the more specific level 2 and 3 recommended data sets. Data elements were broadly divided into (i) patient characteristics; (ii) comorbidities; (iii) current medications; (iv) lesion treated; (v) procedure; (vi) bypass; (vii) endarterectomy (viii) catheter based...

  17. Comparison of Various Nuclear Localization Signal-Fused Cas9 Proteins and Cas9 mRNA for Genome Editing in Zebrafish.

    Science.gov (United States)

    Hu, Peinan; Zhao, Xueying; Zhang, Qinghua; Li, Weiming; Zu, Yao

    2018-03-02

    The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system has been proven to be an efficient and precise genome editing technology in various organisms. However, the gene editing efficiencies of Cas9 proteins with a nuclear localization signal (NLS) fused to different termini and Cas9 mRNA have not been systematically compared. Here, we compared the ability of Cas9 proteins with NLS fused to the N-, C-, or both the N- and C-termini and N-NLS-Cas9-NLS-C mRNA to target two sites in the tyr gene and two sites in the gol gene related to pigmentation in zebrafish. Phenotypic analysis revealed that all types of Cas9 led to hypopigmentation in similar proportions of injected embryos. Genome analysis by T7 Endonuclease I (T7E1) assays demonstrated that all types of Cas9 similarly induced mutagenesis in four target sites. Sequencing results further confirmed that a high frequency of indels occurred in the target sites ( tyr1 > 66%, tyr2 > 73%, gol1 > 50%, and gol2 > 35%), as well as various types (more than six) of indel mutations observed in all four types of Cas9-injected embryos. Furthermore, all types of Cas9 showed efficient targeted mutagenesis on multiplex genome editing, resulting in multiple phenotypes simultaneously. Collectively, we conclude that various NLS-fused Cas9 proteins and Cas9 mRNAs have similar genome editing efficiencies on targeting single or multiple genes, suggesting that the efficiency of CRISPR/Cas9 genome editing is highly dependent on guide RNAs (gRNAs) and gene loci. These findings may help to simplify the selection of Cas9 for gene editing using the CRISPR/Cas9 system. Copyright © 2018 Hu et al.

  18. Meta-analysis of individual registry results enhances international registry collaboration.

    Science.gov (United States)

    Paxton, Elizabeth W; Mohaddes, Maziar; Laaksonen, Inari; Lorimer, Michelle; Graves, Stephen E; Malchau, Henrik; Namba, Robert S; Kärrholm, John; Rolfson, Ola; Cafri, Guy

    2018-03-28

    Background and purpose - Although common in medical research, meta-analysis has not been widely adopted in registry collaborations. A meta-analytic approach in which each registry conducts a standardized analysis on its own data followed by a meta-analysis to calculate a weighted average of the estimates allows collaboration without sharing patient-level data. The value of meta-analysis as an alternative to individual patient data analysis is illustrated in this study by comparing the risk of revision of porous tantalum cups versus other uncemented cups in primary total hip arthroplasties from Sweden, Australia, and a US registry (2003-2015). Patients and methods - For both individual patient data analysis and meta-analysis approaches a Cox proportional hazard model was fit for time to revision, comparing porous tantalum (n = 23,201) with other uncemented cups (n = 128,321). Covariates included age, sex, diagnosis, head size, and stem fixation. In the meta-analysis approach, treatment effect size (i.e., Cox model hazard ratio) was calculated within each registry and a weighted average for the individual registries' estimates was calculated. Results - Patient-level data analysis and meta-analytic approaches yielded the same results with the porous tantalum cups having a higher risk of revision than other uncemented cups (HR (95% CI) 1.6 (1.4-1.7) and HR (95% CI) 1.5 (1.4-1.7), respectively). Adding the US cohort to the meta-analysis led to greater generalizability, increased precision of the treatment effect, and similar findings (HR (95% CI) 1.6 (1.4-1.7)) with increased risk of porous tantalum cups. Interpretation - The meta-analytic technique is a viable option to address privacy, security, and data ownership concerns allowing more expansive registry collaboration, greater generalizability, and increased precision of treatment effects.

  19. Tuberculose pulmonaire révélée par un purpura thrombopénique chez l'enfant-à propos d'un cas clinique observé au service de pédiatrie des Cliniques Universitaires de Lubumbashi

    Science.gov (United States)

    Lubala, Toni Kasole; Mutombo, Augustin Mulangu; Munkana, Arthur Ndundula; Manika, Michel Muteya

    2012-01-01

    Nous rapportons le cas d'un enfant de 7 ans, de sexe masculin ayant présenté un purpura thrombopénique avec épistaxis, hématémèse, otorragies et pétéchies généralisées. Durant la même hospitalisation, nous avons mis en évidence une tuberculose pulmonaire documentée par la présence de bacilles acido-alcoolo résistants à l'examen des crachats. Nous avons observé une majoration du taux de plaquettes en une semaine de corticothérapie intraveineuse à haute dose, avant l'instauration d'une poly chimiothérapie antituberculeuse. Nous rappelons également la controverse que suscite la prise en charge de cette association rarement rapportée. PMID:23077696

  20. A Registry Framework Enabling Patient-Centred Care.

    Science.gov (United States)

    Bellgard, Matthew I; Napier, Kathryn; Render, Lee; Radochonski, Maciej; Lamont, Leanne; Graham, Caroline; Wilton, Steve D; Fletcher, Sue; Goldblatt, Jack; Hunter, Adam A; Weeramanthri, Tarun

    2015-01-01

    Clinical decisions rely on expert knowledge that draws on quality patient phenotypic and physiological data. In this regard, systems that can support patient-centric care are essential. Patient registries are a key component of patient-centre care and can come in many forms such as disease-specific, recruitment, clinical, contact, post market and surveillance. There are, however, a number of significant challenges to overcome in order to maximise the utility of these information management systems to facilitate improved patient-centred care. Registries need to be harmonised regionally, nationally and internationally. However, the majority are implemented as standalone systems without consideration for data standards or system interoperability. Hence the task of harmonisation can become daunting. Fortunately, there are strategies to address this. In this paper, a disease registry framework is outlined that enables efficient deployment of national and international registries that can be modified dynamically as registry requirements evolve. This framework provides a basis for the development and implementation of data standards and enables patients to seamlessly belong to multiple registries. Other significant advances include the ability for registry curators to create and manage registries themselves without the need to contract software developers, and the concept of a registry description language for ease of registry template sharing.

  1. RItA: The Italian severe/uncontrolled asthma registry.

    Science.gov (United States)

    Maio, S; Baldacci, S; Bresciani, M; Simoni, M; Latorre, M; Murgia, N; Spinozzi, F; Braschi, M; Antonicelli, L; Brunetto, B; Iacovacci, P; Roazzi, P; Pini, C; Pata, M; La Grasta, L; Paggiaro, P; Viegi, G

    2018-03-01

    The Italian severe/uncontrolled asthma (SUA) web-based registry encompasses demographic, clinical, functional, and inflammatory data; it aims to raise SUA awareness, identifying specific phenotypes and promoting optimal care. Four hundred and ninety three adult patients from 27 Italian centers (recruited in 2011-2014) were analyzed. Mean age was 53.8 years. SUA patients were more frequently female (60.6%), with allergic asthma (83.1%). About 30% showed late onset of asthma diagnosis/symptoms (>40 years); the mean age for asthma symptoms onset was 30.2 years and for asthma diagnosis 34.4 years. 97.1% used ICS (dose 2000 BDP), 93.6% LABA in association with ICS, 53.3% LTRAs, 64.1% anti-IgE, 10.7% theophylline, and 16.0% oral corticosteroids. Mean FEV 1 % pred of 75.1%, median values of 300/mm 3 of blood eosinophil count, 323 kU/L of serum total IgE, and 24 ppb of FENO were shown. Most common comorbidities were allergic rhinitis (62.4%), gastroesophageal reflux (42.1%), sinusitis (37.9%), nasal polyposis (30.2%), and allergic conjunctivitis (30.2%). 55.7% of SUA patients had exacerbations in the last 12 months, 9.7% emergency department visits, and 7.3% hospitalizations. Factors associated with exacerbation risk were obesity (OR, 95% CI 2.46, 1.11-5.41), psychic disorders (2.87, 0.89-9.30-borderline), nasal polyps (1.86, 0.88-3.89-borderline), partial/poor asthma treatment adherence (2.54, 0.97-6.67-borderline), and anti-IgE use in a protective way (0.26, 0.12-0.53). Comparisons to severe asthma multicenter studies and available registries showed data consistency across European and American populations. An international effort in the implementation of SUA patients' registries could help to better understand the clinical features and to manage severe asthma, representing a non-negligible socioeconomic burden for health services. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  2. Where the Semantic Web and Web 2.0 Meet Format Risk Management: P2 Registry

    Directory of Open Access Journals (Sweden)

    David Tarrant

    2011-03-01

    Full Text Available The Web is increasingly becoming a platform for linked data. This means making connections and adding value to data on the Web. As more data becomes openly available and more people are able to use the data, it becomes more powerful. An example is file format registries and the evaluation of format risks. Here the requirement for information is now greater than the effort that any single institution can put into gathering and collating this information. Recognising that more is better, the creators of PRONOM, JHOVE, GDFR and others are joining to lead a new initiative: the Unified Digital Format Registry. Ahead of this effort, a new RDF-based framework for structuring and facilitating file format data from multiple sources, including PRONOM, has demonstrated it is able to produce more links, and thus provide more answers to digital preservation questions - about format risks, applications, viewers and transformations - than the native data alone. This paper will describe this registry, P2, and its services, show how it can be used, and provide examples where it delivers more answers than the contributing resources. The P2 Registry is a reference platform to allow and encourage publication of preservation data, and also an examplar of what can be achieved if more data is published openly online as simple machine-readable documents. This approach calls for the active participation of the digital preservation community to contribute data by simply publishing it openly on the Web as linked data.

  3. Harnessing CRISPR-Cas systems for bacterial genome editing.

    Science.gov (United States)

    Selle, Kurt; Barrangou, Rodolphe

    2015-04-01

    Manipulation of genomic sequences facilitates the identification and characterization of key genetic determinants in the investigation of biological processes. Genome editing via clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) constitutes a next-generation method for programmable and high-throughput functional genomics. CRISPR-Cas systems are readily reprogrammed to induce sequence-specific DNA breaks at target loci, resulting in fixed mutations via host-dependent DNA repair mechanisms. Although bacterial genome editing is a relatively unexplored and underrepresented application of CRISPR-Cas systems, recent studies provide valuable insights for the widespread future implementation of this technology. This review summarizes recent progress in bacterial genome editing and identifies fundamental genetic and phenotypic outcomes of CRISPR targeting in bacteria, in the context of tool development, genome homeostasis, and DNA repair. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. CRISPR-Cas adaptation: insights into the mechanism of action.

    Science.gov (United States)

    Amitai, Gil; Sorek, Rotem

    2016-02-01

    Since the first demonstration that CRISPR-Cas systems provide bacteria and archaea with adaptive immunity against phages and plasmids, numerous studies have yielded key insights into the molecular mechanisms governing how these systems attack and degrade foreign DNA. However, the molecular mechanisms underlying the adaptation stage, in which new immunological memory is formed, have until recently represented a major unresolved question. In this Progress article, we discuss recent discoveries that have shown both how foreign DNA is identified by the CRISPR-Cas adaptation machinery and the molecular basis for its integration into the chromosome to form an immunological memory. Furthermore, we describe the roles of each of the specific CRISPR-Cas components that are involved in memory formation, and consider current models for their evolutionary origin.

  5. Exploiting CRISPR/Cas: Interference Mechanisms and Applications

    Directory of Open Access Journals (Sweden)

    André Plagens

    2013-07-01

    Full Text Available The discovery of biological concepts can often provide a framework for the development of novel molecular tools, which can help us to further understand and manipulate life. One recent example is the elucidation of the prokaryotic adaptive immune system, clustered regularly interspaced short palindromic repeats (CRISPR/CRISPR-associated (Cas that protects bacteria and archaea against viruses or conjugative plasmids. The immunity is based on small RNA molecules that are incorporated into versatile multi-domain proteins or protein complexes and specifically target viral nucleic acids via base complementarity. CRISPR/Cas interference machines are utilized to develop novel genome editing tools for different organisms. Here, we will review the latest progress in the elucidation and application of prokaryotic CRISPR/Cas systems and discuss possible future approaches to exploit the potential of these interference machineries.

  6. Applications of CRISPR/Cas9 in retinal degenerative diseases

    Science.gov (United States)

    Peng, Ying-Qian; Tang, Luo-Sheng; Yoshida, Shigeo; Zhou, Ye-Di

    2017-01-01

    Gene therapy is a potentially effective treatment for retinal degenerative diseases. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system has been developed as a new genome-editing tool in ophthalmic studies. Recent advances in researches showed that CRISPR/Cas9 has been applied in generating animal models as well as gene therapy in vivo of retinitis pigmentosa (RP) and leber congenital amaurosis (LCA). It has also been shown as a potential attempt for clinic by combining with other technologies such as adeno-associated virus (AAV) and induced pluripotent stem cells (iPSCs). In this review, we highlight the main points of further prospect of using CRISPR/Cas9 in targeting retinal degeneration. We also emphasize the potential applications of this technique in treating retinal degenerative diseases. PMID:28503441

  7. CRISPR/Cas9 mediates efficient conditional mutagenesis in Drosophila.

    Science.gov (United States)

    Xue, Zhaoyu; Wu, Menghua; Wen, Kejia; Ren, Menda; Long, Li; Zhang, Xuedi; Gao, Guanjun

    2014-09-05

    Existing transgenic RNA interference (RNAi) methods greatly facilitate functional genome studies via controlled silencing of targeted mRNA in Drosophila. Although the RNAi approach is extremely powerful, concerns still linger about its low efficiency. Here, we developed a CRISPR/Cas9-mediated conditional mutagenesis system by combining tissue-specific expression of Cas9 driven by the Gal4/upstream activating site system with various ubiquitously expressed guide RNA transgenes to effectively inactivate gene expression in a temporally and spatially controlled manner. Furthermore, by including multiple guide RNAs in a transgenic vector to target a single gene, we achieved a high degree of gene mutagenesis in specific tissues. The CRISPR/Cas9-mediated conditional mutagenesis system provides a simple and effective tool for gene function analysis, and complements the existing RNAi approach. Copyright © 2014 Xue et al.

  8. CRISPR-Cas9 gene editing in honeybee and pig

    DEFF Research Database (Denmark)

    Pen, Anja

    2018-01-01

    Creating animal models by using genome modification has gotten significantly more accessible thanks to the CRISPR-Cas9 technique. In this study, we aimed to the implement the CRISPR-Cas9 methodology in the European honeybee (Apis mellifera) and pig (Sus scrofa) for generation of animal models. We...... want to use these animal models to study the development of honeybees and the pathology of amyotrophic lateral sclerosis (ALS) in a pig model of human disease. In order to simplify the production of these animal models, we test the use of sperm mediated gene transfer (SMGT) in combination with CRISPR...... mechanisms of honeybee development using genome modification will aid in uncovering these complex genetic regulatory systems. In honeybees, we have attempted to induce genome modification in the cinnabar gene through microinjection and feeding of CRISPR-Cas9 components to larvae. Additionally, we tested...

  9. Determination of local chromatin composition by CasID.

    Science.gov (United States)

    Schmidtmann, Elisabeth; Anton, Tobias; Rombaut, Pascaline; Herzog, Franz; Leonhardt, Heinrich

    2016-09-02

    Chromatin structure and function are determined by a plethora of proteins whose genome-wide distribution is typically assessed by immunoprecipitation (ChIP). Here, we developed a novel tool to investigate the local chromatin environment at specific DNA sequences. We combined the programmable DNA binding of dCas9 with the promiscuous biotin ligase BirA* (CasID) to biotinylate proteins in the direct vicinity of specific loci. Subsequent streptavidin-mediated precipitation and mass spectrometry identified both known and previously unknown chromatin factors associated with repetitive telomeric, major satellite and minor satellite DNA. With super-resolution microscopy, we confirmed the localization of the putative transcription factor ZNF512 at chromocenters. The versatility of CasID facilitates the systematic elucidation of functional protein complexes and locus-specific chromatin composition.

  10. Exploiting CRISPR/Cas: Interference Mechanisms and Applications

    Science.gov (United States)

    Richter, Hagen; Randau, Lennart; Plagens, André

    2013-01-01

    The discovery of biological concepts can often provide a framework for the development of novel molecular tools, which can help us to further understand and manipulate life. One recent example is the elucidation of the prokaryotic adaptive immune system, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) that protects bacteria and archaea against viruses or conjugative plasmids. The immunity is based on small RNA molecules that are incorporated into versatile multi-domain proteins or protein complexes and specifically target viral nucleic acids via base complementarity. CRISPR/Cas interference machines are utilized to develop novel genome editing tools for different organisms. Here, we will review the latest progress in the elucidation and application of prokaryotic CRISPR/Cas systems and discuss possible future approaches to exploit the potential of these interference machineries. PMID:23857052

  11. Les Brulures Electriques par Haut Voltage - A Propos de 10 Cas

    Science.gov (United States)

    Belmir, R.; Fejjal, N.; El Omari, M.; El Mazouz, S.; Gharib, N.; Abassi, A.; Belmahi, A.

    2008-01-01

    Summary Les accidents électriques par haute tension (AEHT) provoquent des brûlures profondes par effet Joule le long des axes vasculo-nerveux entre les points d'entrée et de sortie, qui sont le siège de lésions délabrantes. Les Auteurs rapportent une série de dix cas d'AEHT admis au service de chirurgie réparatrice et de brûlés de l'Hôpital Ibn Sina de Rabat à travers laquelle ils étudient les caractéristiques épidémiologiques, cliniques et thérapeutiques. Tous les patients étaient des adultes de sexe masculin dont l'âge moyen était de 31 ans. Dans 70% des cas, ces brûlures étaient secondaires à un contact avec les distributeurs d'électricité avec une surface brûlée inférieure à 20%. Le traitement des lésions électrothermiques a nécessité des interventions itératives avec amputation des segments de membres nécrosés dans 70% des cas, dont les suites étaient marquées par des séquelles fonctionnelles invalidantes. La prévention des AEHT, en particulier pour les accidents du travail au sein des professions exposées, reste fondamentale. PMID:21991124

  12. CAS – A Journey Has Begun in Aotearoa New Zealand

    Directory of Open Access Journals (Sweden)

    Derek Smith

    2008-08-01

    Full Text Available This paper explores a journey through hand-held technology changes in mathematics teaching and learning and raises questions we as mathematics educators should be considering in the shorter and longer term. New Zealand is embarking on a Computer Algebraic Systems (CAS Pilot Programme in secondary school mathematics. The Ministry of Education and the New Zealand Qualifications Authority have selected secondary schools to be part of a pilot programme in the use of CAS technology in mathematics classes. The aim of the pilot programme is to improve teaching and learning of mathematics through the use of this technology. Six schools in 2005 used CAS technology with Year 9 (13-14 year olds students and, an additional 16 schools joined the programme in 2006. The pilot is planned to continue with an increasing number of schools in subsequent years. By the time students in the pilot schools reach Years 11, 12 and 13, alternative external assessments using the CAS technology will be available. Professional development support and assistance in obtaining and using the technology will be provided to the pilot schools. The project's emphasis in 2005 was on the Geometry and Algebra strands; the Statistics strand was added in 2006. By 2010 the first cohort of project programme students will have been through their secondary mathematics education via a CAS environment. New Zealand teachers have only a finite time to get into CAS technology and integrate it into their teaching practice. This paper discusses a research project based on a mathematics department professional development that is linked to the pilot.

  13. A Dutch Nationwide Bariatric Quality Registry: DATO.

    Science.gov (United States)

    Poelemeijer, Youri Q M; Liem, Ronald S L; Nienhuijs, Simon W

    2017-12-22

    In the Netherlands, the number of bariatric procedures increased exponentially in the 90s. To ensure and improve the quality of bariatric surgery, the nationwide Dutch Audit for Treatment of Obesity (DATO) was established in 2014. The audit was coordinated by the Dutch Institute for Clinical Auditing (DICA). This article provides a review of the aforementioned process in establishing a nationwide registry in the Netherlands. In collaboration with the DATO's scientific committee and other stakeholders, an annual list of several external quality indicators was formulated. This list consists of volume, process, and outcome indicators. In addition to the annual external indicators, the database permits individual hospitals to analyze their own data. The dashboard provides several standardized reports and detailed quality indicators, which are updated on a weekly base. Since the start, all 18 Dutch bariatric centers participated in the nationwide audit. A total of 21,941 cases were registered between 2015 and 2016. By 2016, the required variables were registered in 94.3% of all cases. A severe complicated course was seen in 2.87%, and mortality in 0.05% in 2016. The first-year follow-up shows a > 20% TWL in 86.1% of the registered cases. The DATO has become rapidly a mature registry. The well-organized structure of the national audit institution DICA and governmental funding were essential. However, most important were the bariatric teams themselves. The authors believe reporting the results from the registry has already contributed to more knowledge and acceptance by other health care providers.

  14. National registry of hemoglobinopathies in Spain (REPHem).

    Science.gov (United States)

    Cela, Elena; Bellón, José M; de la Cruz, María; Beléndez, Cristina; Berrueco, Rubén; Ruiz, Anna; Elorza, Izaskun; Díaz de Heredia, Cristina; Cervera, Aurea; Vallés, Griselda; Salinas, J Antonio; Coll, M Teresa; Bermúdez, Mar; Prudencio, Marta; Argilés, Bienvenida; Vecilla, Cruz

    2017-07-01

    Although highly prevalent throughout the world, the accurate prevalence of hemoglobinopathies in Spain is unknown. This study presents data on the national registry of hemoglobinopathies of patients with thalassemia major (TM), thalassemia intermedia (TI), and sickle cell disease (SCD) in Spain created in 2014. Fifty centers reported cases retrospectively. Data were registered from neonatal screening or from the first contact at diagnosis until last follow-up or death. Data of the 715 eligible patients were collected: 615 SCD (497 SS, 64 SC, 54 SBeta phenotypes), 73 thalassemia, 9 CC phenotype, and 18 other variants. Most of the SCD patients were born in Spain (65%), and 51% of these were diagnosed at newborn screening. Median age at the first diagnosis was 0.4 years for thalassemia and 1.0 years for SCD. The estimated incidence was 0.002 thalassemia cases and 0.03 SCD cases/1,000 live births. Median age was 8.9 years (0.2-33.7) for thalassemia and 8.1 years (0.2-32.8) for SCD patients. Stroke was registered in 16 SCD cases. Transplantation was performed in 43 TM and 23 SCD patients at a median age of 5.2 and 7.8 years, respectively. Twenty-one patients died (3 TM, 17 SCD, 1 CC) and 200 were lost to follow-up. Causes of death were related to transplantation in three patients with TM and three patients with SCD. Death did not seem to be associated with SCD in six patients, but nine patients died secondary to disease complications. Overall survival was 95% at 15 years of age. The registry provides data about the prevalence of hemoglobinopathies in Spain and will permit future cohort studies and the possibility of comparison with other registries. © 2016 Wiley Periodicals, Inc.

  15. Characterizing a thermostable Cas9 for bacterial genome editing and silencing

    NARCIS (Netherlands)

    Mougiakos, Ioannis; Mohanraju, Prarthana; Bosma, Elleke F.; Vrouwe, Valentijn; Finger Bou, Max; Naduthodi, Mihris I.S.; Gussak, Alex; Brinkman, Rudolf B.L.; Kranenburg, Van Richard; Oost, Van Der John

    2017-01-01

    CRISPR-Cas9-based genome engineering tools have revolutionized fundamental research and biotechnological exploitation of both eukaryotes and prokaryotes. However, the mesophilic nature of the established Cas9 systems does not allow for applications that require enhanced stability, including

  16. Characterizing a thermostable Cas9 for bacterial genome editing and silencing

    DEFF Research Database (Denmark)

    Mougiakos, Ioannis; Mohanraju, Prarthana; Bosma, Elleke Fenna

    2017-01-01

    CRISPR-Cas9-based genome engineering tools have revolutionized fundamental research and biotechnological exploitation of both eukaryotes and prokaryotes. However, the mesophilic nature of the established Cas9 systems does not allow for applications that require enhanced stability, including...

  17. Danish Registry of Childhood and Adolescent Diabetes

    Directory of Open Access Journals (Sweden)

    Svensson J

    2016-10-01

    Full Text Available Jannet Svensson,1 Charlotte Cerqueira,2 Per Kjærsgaard,3 Lene Lyngsøe,4 Niels Thomas Hertel,5 Mette Madsen,6 Henrik B Mortensen,1 Jesper Johannesen1 1Pediatric and Adolescent Department, Copenhagen University Hospital, Herlev and Gentofte, Herlev, 2Registry Support Centre (East – Epidemiology and Biostatistics, Research Centre for Prevention and Health, Capital Region of Denmark, Glostrup, 3Pediatric Department, County Hospital Herning, Herning, 4Pediatric and Adolescent Department, Nordsjællands Hospital, Hillerød, 5HC Andersen Childrens Hospital, Odense University Hospital, Odense, 6Pediatric Department, Aalborg University Hospital, Aalborg, Denmark Aim: The aims of the Danish Registry of Childhood and Adolescent Diabetes (DanDiabKids are to monitor and improve the quality of care for children and adolescents with diabetes in Denmark and to follow the incidence and prevalence of diabetes. Study population: The study population consists of all children diagnosed with diabetes before the age of 15 years since 1996. Since 2015, every child followed up at a pediatric center (<18 years of age will be included. Main variables: The variables in the registry are the quality indicators, demographic variables, associated conditions, diabetes classification, family history of diabetes, growth parameters, self-care, and treatment variables. The quality indicators are selected based on international consensus of measures of good clinical practice. The indicators are metabolic control as assessed by HbA1c, blood pressure, albuminuria, retinopathy, neuropathy, number of severe hypoglycemic events, and hospitalization with ketoacidosis. Descriptive data: The number of children diagnosed with diabetes is increasing with ~3% per year mainly for type 1 diabetes (ie, 296 new patients <15 years of age were diagnosed in 2014. The disease management has changed dramatically with more children treated intensively with multiple daily injections, insulin pumps

  18. The Danish Neuro-Oncology Registry

    DEFF Research Database (Denmark)

    Hansen, Steinbjørn

    2016-01-01

    AIM OF DATABASE: The Danish Neuro-Oncology Registry (DNOR) was established by the Danish Neuro-Oncology Group as a national clinical database. It was established for the purpose of supporting research and development in adult patients with primary brain tumors in Denmark. STUDY POPULATION: DNOR has...... advantage of reporting indicators is the related multidisciplinary discussions giving a better understanding of what actually is going on, thereby facilitating the work on adjusting the national guidelines in the Danish Neuro-Oncology Group. CONCLUSION: The establishment of DNOR has optimized the quality...

  19. [Computerization and the importance of information in health system, as in health care resources registry].

    Science.gov (United States)

    Troselj, Mario; Fanton, Davor

    2005-01-01

    The possibilities of creating a health care resources registry and its operating in Croatia as well as the importance of information in health system are described. At the Croatian Institute of Public Health, monitoring of human resources is performed through the national Health Workers Registry. It also covers basic data on all health units, bed capacities of health facilities included. The initiated health care computerization has urged the idea of forming one more database on physical resources, i.e. on registered medical devices and equipment, more complete. Linking these databases on health resources would produce a single Health Care Resources Registry. The concept views Health Care Resources Registry as part of the overall health information system with centralized information on the health system. The planned development of segments of a single health information system is based on the implementation of the accepted international standards and common network services. Network services that are based on verified Internet technologies are used within a safe, reliable and closed health computer network, which makes up the health intranet (WAN--Wide Area Network). The resource registry is a software solution based on the relational database that monitors history, thus permitting the data collected over a longer period to be analyzed. Such a solution assumes the existence of a directory service, which would replace the current independent software for the Health Workers Registry. In the Health Care Resources Registry, the basic data set encompasses data objects and attributes from the directory service. The directory service is compatible with the LDAP protocol (Lightweight Directory Access Protocol), providing services uniformly to the current records on human and physical resources. Through the storage of attributes defined according to the HL7 (Health Level Seven) standard, directory service is accessible to all applications of the health information system

  20. Evidence and practice in spine registries A systematic review, and recommendations for future design of registries

    NARCIS (Netherlands)

    van Hooff, M.L.; Jacobs, W.C.H.; Willems, P.C.; Wouters, M.W.J.M.; de Kleuver, M.; Peul, W.C.; Ostelo, R.W.J.G.; Fritzell, P.

    2015-01-01

    Background and purpose-We performed a systematic review and a survey in order to (1) evaluate the evidence for the impact of spine registries on the quality of spine care, and with that, on patient-related outcomes, and (2) evaluate the methodology used to organize, analyze, and report the "quality

  1. The Danish Multiple Sclerosis Registry. History, data collection and validity

    DEFF Research Database (Denmark)

    Koch-Henriksen, N; Rasmussen, S; Stenager, E

    2001-01-01

    The Danish Multiple Sclerosis Registry was formally established in 1956 but started operating in 1949 with a nationwide prevalence survey. Since then, the Registry has continued collecting data on new and old cases of multiple sclerosis (MS) or suspected MS from multiple sources. The Registry...... instrument for monitoring incidence and prevalence, analysing survival, performing genetic analysis, providing unselected patient samples for clinical analyses, performing case-control studies and prospective studies and estimating the need for treatment and care....

  2. CRISPR-Cas9-Mediated Genome Editing in Leishmania donovani.

    Science.gov (United States)

    Zhang, Wen-Wei; Matlashewski, Greg

    2015-07-21

    The prokaryotic CRISPR (clustered regularly interspaced short palindromic repeat)-Cas9, an RNA-guided endonuclease, has been shown to mediate efficient genome editing in a wide variety of organisms. In the present study, the CRISPR-Cas9 system has been adapted to Leishmania donovani, a protozoan parasite that causes fatal human visceral leishmaniasis. We introduced the Cas9 nuclease into L. donovani and generated guide RNA (gRNA) expression vectors by using the L. donovani rRNA promoter and the hepatitis delta virus (HDV) ribozyme. It is demonstrated within that L. donovani mainly used homology-directed repair (HDR) and microhomology-mediated end joining (MMEJ) to repair the Cas9 nuclease-created double-strand DNA break (DSB). The nonhomologous end-joining (NHEJ) pathway appears to be absent in L. donovani. With this CRISPR-Cas9 system, it was possible to generate knockouts without selection by insertion of an oligonucleotide donor with stop codons and 25-nucleotide homology arms into the Cas9 cleavage site. Likewise, we disrupted and precisely tagged endogenous genes by inserting a bleomycin drug selection marker and GFP gene into the Cas9 cleavage site. With the use of Hammerhead and HDV ribozymes, a double-gRNA expression vector that further improved gene-targeting efficiency was developed, and it was used to make precise deletion of the 3-kb miltefosine transporter gene (LdMT). In addition, this study identified a novel single point mutation caused by CRISPR-Cas9 in LdMT (M381T) that led to miltefosine resistance, a concern for the only available oral antileishmanial drug. Together, these results demonstrate that the CRISPR-Cas9 system represents an effective genome engineering tool for L. donovani. Leishmania donovani is the causative agent of fatal visceral leishmaniasis. To understand Leishmania infection and pathogenesis and identify new drug targets for control of leishmaniasis, more-efficient ways to manipulate this parasite genome are required. In this

  3. Les synovites villonodulaires du genou: à propos de 20 cas

    Science.gov (United States)

    Margad, Omar; Boukhris, Jalal; Azriouil, Ouahb; Daoudi, Mohamed; Mortaji, Aziz; Koulali, Khalid

    2017-01-01

    La synovite villonodulaire pigmentée (SVNP) est une prolifération bénigne rare de la synoviale des articulations, des bourses séreuses et des gaines tendineuses, d'étiopathogénie inconnue. Notre travail porte sur 20 cas de SVN du genou colligés à l'hôpital militaire Avicenne de Marrakech sur une période de 9 ans allant de janvier 2000 au décembre 2009 Il vise à identifier les spécificités de cette lésion, et à étudier ses principaux aspects anatomocliniques et pronostiques. L'incidence annuelle était de 2,2 cas par an. Ils étaient 15 hommes et 5 femmes, d'âge moyen de 32,5 ans, atteints du coté droit dans 55%des cas sous un mode mono articulaire chez 18 patients et bi articulaire chez un seul. La douleur et la tuméfaction étaient présentes dans 80% des cas, une masse palpable dans un cas, un syndrome méniscal a été retenu dans un cas, une mono arthrite septique dans 3 circonstances de même qu'un kyste poplité dans 2 autres. L'atteinte était diffuse dans 14 cas (70%), localisée dans 6 cas. L'imagerie par résonnance magnétique(IRM) pratiquée chez 5 patients était évocatrice chez 3, l'arthroscopie diagnostique a été utilisée chez 2 malades. La confirmation s'est faite à chaque fois à l'examen anatomopathlogique. Le traitement a consisté en une synovectomie subtotale dans 15 cas et en l'exérèse de la tumeur dans les autres formes localisées, 2 cas présentant une destruction ostéocartilagineuse ont nécessité une arthroplastie. L'évolution a été marquée par la survenue de 2 récidives sous la forme diffuse avec un recul de 3, 7 ans. On a noté une raideur avec atrophie quadricipitale chez 3 patients et une arthrolyse a été réalisée. Un cas de SVN confirmé par l'histologie s'est révélé être 5 mois après la synovectomie totale un Synovialosarcome monophasique envahissant l'os d'où l'indication de l'amputation. PMID:29255556

  4. Mismatch Negativity Responses in Children with a Diagnosis of Childhood Apraxia of Speech (CAS)

    Science.gov (United States)

    Froud, Karen; Khamis-Dakwar, Reem

    2012-01-01

    Purpose: To evaluate whether a hypothesis suggesting that apraxia of speech results from phonological overspecification could be relevant for childhood apraxia of speech (CAS). Method: High-density EEG was recorded from 5 children with CAS and 5 matched controls, ages 5-8 years, with and without CAS, as they listened to randomized sequences of CV…

  5. Suppression of HBV replication by the expression of nickase- and nuclease dead-Cas9.

    Science.gov (United States)

    Kurihara, Takeshi; Fukuhara, Takasuke; Ono, Chikako; Yamamoto, Satomi; Uemura, Kentaro; Okamoto, Toru; Sugiyama, Masaya; Motooka, Daisuke; Nakamura, Shota; Ikawa, Masato; Mizokami, Masashi; Maehara, Yoshihiko; Matsuura, Yoshiharu

    2017-07-21

    Complete removal of hepatitis B virus (HBV) DNA from nuclei is difficult by the current therapies. Recent reports have shown that a novel genome-editing tool using Cas9 with a single-guide RNA (sgRNA) system can cleave the HBV genome in vitro and in vivo. However, induction of a double-strand break (DSB) on the targeted genome by Cas9 risks undesirable off-target cleavage on the host genome. Nickase-Cas9 cleaves a single strand of DNA, and thereby two sgRNAs are required for inducing DSBs. To avoid Cas9-induced off-target mutagenesis, we examined the effects of the expressions of nickase-Cas9 and nuclease dead Cas9 (d-Cas9) with sgRNAs on HBV replication. The expression of nickase-Cas9 with a pair of sgRNAs cleaved the target HBV genome and suppressed the viral-protein expression and HBV replication in vitro. Moreover, nickase-Cas9 with the sgRNA pair cleaved the targeted HBV genome in mouse liver. Interestingly, d-Cas9 expression with the sgRNAs also suppressed HBV replication in vitro without cleaving the HBV genome. These results suggest the possible use of nickase-Cas9 and d-Cas9 with a pair of sgRNAs for eliminating HBV DNA from the livers of chronic hepatitis B patients with low risk of undesirable off-target mutation on the host genome.

  6. The role of Cas8 in type I CRISPR interference.

    Science.gov (United States)

    Cass, Simon D B; Haas, Karina A; Stoll, Britta; Alkhnbashi, Omer S; Sharma, Kundan; Urlaub, Henning; Backofen, Rolf; Marchfelder, Anita; Bolt, Edward L

    2015-05-05

    CRISPR (clustered regularly interspaced short palindromic repeat) systems provide bacteria and archaea with adaptive immunity to repel invasive genetic elements. Type I systems use 'cascade' [CRISPR-associated (Cas) complex for antiviral defence] ribonucleoprotein complexes to target invader DNA, by base pairing CRISPR RNA (crRNA) to protospacers. Cascade identifies PAMs (protospacer adjacent motifs) on invader DNA, triggering R-loop formation and subsequent DNA degradation by Cas3. Cas8 is a candidate PAM recognition factor in some cascades. We analysed Cas8 homologues from type IB CRISPR systems in archaea Haloferax volcanii (Hvo) and Methanothermobacter thermautotrophicus (Mth). Cas8 was essential for CRISPR interference in Hvo and purified Mth Cas8 protein responded to PAM sequence when binding to nucleic acids. Cas8 interacted physically with Cas5-Cas7-crRNA complex, stimulating binding to PAM containing substrates. Mutation of conserved Cas8 amino acid residues abolished interference in vivo and altered catalytic activity of Cas8 protein in vitro. This is experimental evidence that Cas8 is important for targeting Cascade to invader DNA. © 2015 Authors.

  7. 41 CFR 102-33.130 - If we hire CAS, what are our management responsibilities?

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false If we hire CAS, what are our management responsibilities? 102-33.130 Section 102-33.130 Public Contracts and Property... § 102-33.130 If we hire CAS, what are our management responsibilities? If you hire CAS, you are...

  8. Cas4 Facilitates PAM-Compatible Spacer Selection during CRISPR Adaptation

    NARCIS (Netherlands)

    Kieper, S.N.; Almendros, Cristóbal; Behler, Juliane; McKenzie, R.E.; Luzia De Nóbrega, F.; van Eijkeren-Haagsma, A.C.; Vink, J.N.A.; Hess, Wolfgang R.; Brouns, S.J.J.

    2018-01-01

    CRISPR-Cas systems adapt their immunological memory against their invaders by integrating short DNA fragments into clustered regularly interspaced short palindromic repeat (CRISPR) loci. While Cas1 and Cas2 make up the core machinery of the CRISPR integration process, various class I and II

  9. Cas4 Facilitates PAM-Compatible Spacer Selection during CRISPR Adaptation

    NARCIS (Netherlands)

    Kieper, Sebastian N.; Almendros, Cristóbal; Behler, Juliane; McKenzie, Rebecca E.; Nobrega, Franklin L.; Haagsma, Anna C.; Vink, Jochem N.A.; Hess, Wolfgang R.; Brouns, Stan J.J.

    2018-01-01

    CRISPR-Cas systems adapt their immunological memory against their invaders by integrating short DNA fragments into clustered regularly interspaced short palindromic repeat (CRISPR) loci. While Cas1 and Cas2 make up the core machinery of the CRISPR integration process, various class I and II

  10. On the Integration of Computer Algebra Systems (CAS) by Canadian Mathematicians: Results of a National Survey

    Science.gov (United States)

    Buteau, Chantal; Jarvis, Daniel H.; Lavicza, Zsolt

    2014-01-01

    In this article, we outline the findings of a Canadian survey study (N = 302) that focused on the extent of computer algebra systems (CAS)-based technology use in postsecondary mathematics instruction. Results suggest that a considerable number of Canadian mathematicians use CAS in research and teaching. CAS use in research was found to be the…

  11. Inconclusive studies on possible CRISPR-Cas off-targets should ...

    Indian Academy of Sciences (India)

    Sandeep Chakraborty

    Published online: 30 April 2018. Keywords. ... in gene-editing technologies have resulted from the simplicity of the single effector (Cas9) class 2 CRISPR-Cas ... a Cas9/gRNA concentration dependence on off-target activity (Pattanayak et al.

  12. Evaluating the completeness of the national ALS registry, United States.

    Science.gov (United States)

    Kaye, Wendy E; Wagner, Laurie; Wu, Ruoming; Mehta, Paul

    2018-02-01

    Our objective was to evaluate the completeness of the United States National ALS Registry (Registry). We compared persons with ALS who were passively identified by the Registry with those actively identified in the State and Metropolitan Area ALS Surveillance project. Cases in the two projects were matched using a combination of identifiers, including, partial social security number, name, date of birth, and sex. The distributions of cases from the two projects that matched/did not match were compared and Chi-square tests conducted to determine statistical significance. There were 5883 ALS cases identified by the surveillance project. Of these, 1116 died before the Registry started, leaving 4767 cases. We matched 2720 cases from the surveillance project to those in the Registry. The cases identified by the surveillance project that did not match cases in the Registry were more likely to be non-white, Hispanic, less than 65 years of age, and from western states. The methods used by the Registry to identify ALS cases, i.e. national administrative data and self-registration, worked well but missed cases. These findings suggest that developing strategies to identify and promote the Registry to those who were more likely to be missing, e.g. non-white and Hispanic, could be beneficial to improving the completeness of the Registry.

  13. The Three Mile Island Population Registry.

    Science.gov (United States)

    Goldhaber, M K; Tokuhata, G K; Digon, E; Caldwell, G G; Stein, G F; Lutz, G; Gur, D

    1983-01-01

    Shortly after the March 28, 1979, accident at the Three Mile Island (TMI) nuclear plant outside Harrisburg, Pa., the Pennsylvania Department of Health, in conjunction with the Centers for Disease Control and the U.S. Bureau of the Census, conducted a census of the 35,930 persons residing within 5 miles of the plant. With the help of 150 enumerators, demographic and health-related information was collected on each person to provide baseline data for future short- and long-term epidemiologic studies of the effects of the accident. Individual radiation doses were estimated on the basis of residential location and the amount of time each person spent in the 5-mile area during the 10 days after the accident. Health and behavioral resurveys of the population will be conducted approximately every 5 years. Population-mobility, morbidity, and mortality will be studied yearly by matching the TMI Population Registry with postal records, cancer registry records, and death certificate data. Because the radiation dose from TMI was extremely small, any increase in morbidity or mortality attributable to the accident would be so small as not to be measurable by present methods; however, adverse health effects as a result of psychological stress may occur. Also, a temporary increase in reporting of disease could occur because of increased surveillance and attention to health.

  14. Pediatric Contact Dermatitis Registry Inaugural Case Data.

    Science.gov (United States)

    Goldenberg, Alina; Mousdicas, Nico; Silverberg, Nanette; Powell, Douglas; Pelletier, Janice L; Silverberg, Jonathan I; Zippin, Jonathan; Fonacier, Luz; Tosti, Antonella; Lawley, Leslie; Wu Chang, Mary; Scheman, Andrew; Kleiner, Gary; Williams, Judith; Watsky, Kalman; Dunnick, Cory A; Frederickson, Rachel; Matiz, Catalina; Chaney, Keri; Estes, Tracy S; Botto, Nina; Draper, Michelle; Kircik, Leon; Lugo-Somolinos, Aida; Machler, Brian; Jacob, Sharon E

    2016-01-01

    Little is known about the epidemiology of allergic contact dermatitis (ACD) in US children. More widespread diagnostic confirmation through epicutaneous patch testing is needed. The aim was to quantify patch test results from providers evaluating US children. The study is a retrospective analysis of deidentified patch test results of children aged 18 years or younger, entered by participating providers in the Pediatric Contact Dermatitis Registry, during the first year of data collection (2015-2016). One thousand one hundred forty-two cases from 34 US states, entered by 84 providers, were analyzed. Sixty-five percent of cases had one or more positive patch test (PPT), with 48% of cases having 1 or more relevant positive patch test (RPPT). The most common PPT allergens were nickel (22%), fragrance mix I (11%), cobalt (9.1%), balsam of Peru (8.4%), neomycin (7.2%), propylene glycol (6.8%), cocamidopropyl betaine (6.4%), bacitracin (6.2%), formaldehyde (5.7%), and gold (5.7%). This US database provides multidisciplinary information on pediatric ACD, rates of PPT, and relevant RPPT reactions, validating the high rates of pediatric ACD previously reported in the literature. The registry database is the largest comprehensive collection of US-only pediatric patch test cases on which future research can be built. Continued collaboration between patients, health care providers, manufacturers, and policy makers is needed to decrease the most common allergens in pediatric consumer products.

  15. The national registry for radiation workers

    International Nuclear Information System (INIS)

    Kendall, G.M.; Dennis, J.A.

    1985-01-01

    The National Registry for Radiation Workers (NRRW) was set up by the National Radiological Protection Board in 1976. The analysis of registry data has four aims: a) To determine whether there is any evidence of differences in the causes of and ages at death of workers exposed to different levels of radiation and, if any differences are found, whether it seems likely that they can be attributed to radiation. b) To estimate the magnitude of the risk, if any differences are found, that seem likely to be attributable to radiation. c) To estimate bounds to the possible risk for particular types of malignancy, such as leukemia. d) To compare the mortality experience of radiation workers with national mortality data and also with that of other industrial groups for whom data exist. If current estimates of the risks of ionizing radiation are correct, very few deaths will be induced in the study population and it will be impossible to detect them statistically. The NRRW currently includes records for over 60,000 individuals. 6 refs

  16. Patient reported outcomes in hip arthroplasty registries.

    Science.gov (United States)

    Paulsen, Aksel

    2014-05-01

    PROs are used increasingly in orthopedics and in joint registries, but still many aspects of use in this area have not been examined in depth. To be able to introduce PROs in the DHR in a scientific fashion, my studies were warranted; the feasibility of four often used PROs (OHS, HOOS, EQ-5D and SF-12) was examined in a registry context. Having the PROs in the target language is an absolute necessity, so I translated, cross-culturally adapted and validated a Danish language version of an often used PRO (OHS), since this PRO had no properly developed Danish language version. To minimize data loss and to maximize the data quality I validated our data capture procedure, an up to date AFP system, by comparing scannable, paper-based PROs, with manual single-key- and double-key entered data. To help further registry-PRO studies, I calculated the number of patients needed to discriminate between subgroups of age, sex, diagnosis, and prosthesis type for each of four often used PROs (OHS, HOOS, EQ-5D and SF-12), and to simplify the clinical interpretation of PRO scores and PRO change scores in PRO studies, I estimated MCII and PASS for two often used PROs (EQ-5D and HOOS). The feasibility study included 5,747 THA patients registered in the DHR, and I found only minor differences between the disease-specific and the generic PROs regarding ceiling and floor effects as well as discarded items. The HOOS, the OHS, the SF-12, and the EQ-5D are all appropriate PROs for administration in a hip registry. I found that group sizes from 51 to 1,566 were needed for subgroup analysis, depending on descriptive factors and choice of PRO. The AFP study included 200 THA patients (398 PROs, 4,875 items and 21,887 data fields), and gave excellent results provided use of highly structured questionnaires. OMR performed equally as well as manual double-key entering, and better than single-key entering. The PRO translation and validation study included 2,278 patients (and 212 patients for the test

  17. Apport de l'imagerie dans le diagnostic des sacroiliites infectieuses : à propos de 19 cas

    Science.gov (United States)

    Abid, Hanen; Chaabouni, Salim; Frikha, Faten; Toumi, Nozha; Souissi, Basma; Lahiani, Dorra; Bahloul, Zouhir; Ben Mahfoudh, Khaireddine

    2014-01-01

    Les sacro-iliites infectieuses méritent d’être mieux connues. Leur diagnostic est souvent retardé en raison d'une symptomatologie trompeuse et des diffcultés d'exploration de l'articulation sacro-iliaque. Notre travail est basé sur une étude rétrospective portant sur les cas de SII, recueillis sur une période comprise entre 1997 et 2008 dans notre centre universitaire Sfax-Tunisie. Le diagnostic de sacro-iliite était retenu en présence d'arguments cliniques et radiologiques d'atteinte sacroiliaque. Nous rapportons dix neuf cas de sacroiliites infectieuses (10 hommes et 9 femmes), avec un âge moyen de 32 ans. L'atteinte était unilatérale dans tous les cas. Les radiographies standard faites dans tous les cas ont été suggestives dans 14 cas et normales dans les autres cas. La TDM faite dans 13 cas a montré, un abcès des parties molles dans 8 cas et un séquestre osseux dans 2 cas. L'IRM réalisée dans 8 cas, a objectivé une infiltration des parties molles dans tous les cas et un abcès dans 3 cas. Le germe a été identifié dans 9 cas (3 cas de tuberculose, 3 cas de brucellose, 2 sacro-iliites à pyogène et un cas de candidose). Cette identification était faite par biopsie dans 3 cas, hémocultures dans 2 cas, prélèvement au niveau de la porte d'entrée dans 1 cas et sérodiagnostic dans 3 cas. Pour les autres cas, l'origine pyogène a été retenue sur des arguments cliniques et biologiques. L'imagerie joue un rôle primordial dans le diagnostic précoce et l'orientation étiologique d'une sacroiliite infectieuse. PMID:25120884

  18. Genome Editing in Penicillium chrysogenum Using Cas9 Ribonucleoprotein Particles

    NARCIS (Netherlands)

    Pohl, Carsten; Mózsik, László; Driessen, Arnold J M; Bovenberg, Roel A L; Nygård, Yvonne I; Braman, Jeffrey Carl

    Several CRISPR/Cas9 tools have been recently established for precise genome editing in a wide range of filamentous fungi. This genome editing platform offers high flexibility in target selection and the possibility of introducing genetic deletions without the introduction of transgenic sequences .

  19. CRISPR-Cas systems: Prokaryotes upgrade to adaptive immunity.

    Science.gov (United States)

    Barrangou, Rodolphe; Marraffini, Luciano A

    2014-04-24

    Clustered regularly interspaced short palindromic repeats (CRISPR), and associated proteins (Cas) comprise the CRISPR-Cas system, which confers adaptive immunity against exogenic elements in many bacteria and most archaea. CRISPR-mediated immunization occurs through the uptake of DNA from invasive genetic elements such as plasmids and viruses, followed by its integration into CRISPR loci. These loci are subsequently transcribed and processed into small interfering RNAs that guide nucleases for specific cleavage of complementary sequences. Conceptually, CRISPR-Cas shares functional features with the mammalian adaptive immune system, while also exhibiting characteristics of Lamarckian evolution. Because immune markers spliced from exogenous agents are integrated iteratively in CRISPR loci, they constitute a genetic record of vaccination events and reflect environmental conditions and changes over time. Cas endonucleases, which can be reprogrammed by small guide RNAs have shown unprecedented potential and flexibility for genome editing and can be repurposed for numerous DNA targeting applications including transcriptional control. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Methods for Optimizing CRISPR-Cas9 Genome Editing Specificity

    Science.gov (United States)

    Tycko, Josh; Myer, Vic E.; Hsu, Patrick D.

    2016-01-01

    Summary Advances in the development of delivery, repair, and specificity strategies for the CRISPR-Cas9 genome engineering toolbox are helping researchers understand gene function with unprecedented precision and sensitivity. CRISPR-Cas9 also holds enormous therapeutic potential for the treatment of genetic disorders by directly correcting disease-causing mutations. Although the Cas9 protein has been shown to bind and cleave DNA at off-target sites, the field of Cas9 specificity is rapidly progressing with marked improvements in guide RNA selection, protein and guide engineering, novel enzymes, and off-target detection methods. We review important challenges and breakthroughs in the field as a comprehensive practical guide to interested users of genome editing technologies, highlighting key tools and strategies for optimizing specificity. The genome editing community should now strive to standardize such methods for measuring and reporting off-target activity, while keeping in mind that the goal for specificity should be continued improvement and vigilance. PMID:27494557

  1. 48 CFR 9903.201-2 - Types of CAS coverage.

    Science.gov (United States)

    2010-10-01

    ..., OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST... to the same cost accounting practices. The term includes Government-owned contractor-operated (GOCO... would prime contracts awarded to the same business unit. In measuring total net CAS-covered awards for a...

  2. Maximizing mutagenesis with solubilized CRISPR-Cas9 ribonucleoprotein complexes.

    Science.gov (United States)

    Burger, Alexa; Lindsay, Helen; Felker, Anastasia; Hess, Christopher; Anders, Carolin; Chiavacci, Elena; Zaugg, Jonas; Weber, Lukas M; Catena, Raul; Jinek, Martin; Robinson, Mark D; Mosimann, Christian

    2016-06-01

    CRISPR-Cas9 enables efficient sequence-specific mutagenesis for creating somatic or germline mutants of model organisms. Key constraints in vivo remain the expression and delivery of active Cas9-sgRNA ribonucleoprotein complexes (RNPs) with minimal toxicity, variable mutagenesis efficiencies depending on targeting sequence, and high mutation mosaicism. Here, we apply in vitro assembled, fluorescent Cas9-sgRNA RNPs in solubilizing salt solution to achieve maximal mutagenesis efficiency in zebrafish embryos. MiSeq-based sequence analysis of targeted loci in individual embryos using CrispRVariants, a customized software tool for mutagenesis quantification and visualization, reveals efficient bi-allelic mutagenesis that reaches saturation at several tested gene loci. Such virtually complete mutagenesis exposes loss-of-function phenotypes for candidate genes in somatic mutant embryos for subsequent generation of stable germline mutants. We further show that targeting of non-coding elements in gene regulatory regions using saturating mutagenesis uncovers functional control elements in transgenic reporters and endogenous genes in injected embryos. Our results establish that optimally solubilized, in vitro assembled fluorescent Cas9-sgRNA RNPs provide a reproducible reagent for direct and scalable loss-of-function studies and applications beyond zebrafish experiments that require maximal DNA cutting efficiency in vivo. © 2016. Published by The Company of Biologists Ltd.

  3. Cas A-A Y2K status report

    Science.gov (United States)

    Rudnick, L.

    2001-05-01

    Cas A has continued to be a rich source of information as new telescopes and detailed observations have become available. In this Y2K update, I focus on the observational findings over the last five years in the areas of ejecta mapping, hydrodynamic structure and kinematics, and high energy particles. Readers are unfortunately left to their own devices on the intriguing point source. .

  4. Application of the nanobiotechnology with the system CRISP-Cas

    Directory of Open Access Journals (Sweden)

    Liceth Xiomara Sáenz-Castiblanco

    2017-12-01

    Full Text Available Introduction: Nanobiotechnology and synthetic biology are sciences that impact today with the launching of innovative and beneficial applications for the human being. These sciences have been amalgamated to manufacture new components for the construction of totally artificial cells and the creation of synthetic biomolecules. Objective: To know the applications of nanobiotechnology related to the use of the system CRISPR/Cas in the storage of bacterial DNA and therapeutic alternatives. Materials and methods: A bibliographical review on the main applications of nanobiotechnology was carried out in ScienceDirect, SciELO, PubMed databases and in magazines such as: Nature Biotechnology, Biochemistry, Science and Journal Microbiology. Results: The literature review describes and analyzes the new nanobiotechnology applications used to write information in the genetic code of bacterial cells, in which the system is used based on short grouped and regularly interspaced palindromic repetitions (CRISPR/Cas and the production of synthetic DNA, as well as therapeutic alternatives related to gene therapy. Conclusion: Among the nanobiotechnology applications, two methods to record information in the DNA of bacterial cells Escherichia coli and Sulfolobus Tokodai have been shown, which are linked to the use of the system CRISPR/Cas and the production of synthetic DNA, as well as the use of CRISPR/Cas in gene and cellular therapy.

  5. Phage Genetic Engineering Using CRISPR–Cas Systems

    Directory of Open Access Journals (Sweden)

    Asma Hatoum-Aslan

    2018-06-01

    Full Text Available Since their discovery over a decade ago, the class of prokaryotic immune systems known as CRISPR–Cas have afforded a suite of genetic tools that have revolutionized research in model organisms spanning all domains of life. CRISPR-mediated tools have also emerged for the natural targets of CRISPR–Cas immunity, the viruses that specifically infect bacteria, or phages. Despite their status as the most abundant biological entities on the planet, the majority of phage genes have unassigned functions. This reality underscores the need for robust genetic tools to study them. Recent reports have demonstrated that CRISPR–Cas systems, specifically the three major types (I, II, and III, can be harnessed to genetically engineer phages that infect diverse hosts. Here, the mechanisms of each of these systems, specific strategies used, and phage editing efficacies will be reviewed. Due to the relatively wide distribution of CRISPR–Cas systems across bacteria and archaea, it is anticipated that these immune systems will provide generally applicable tools that will advance the mechanistic understanding of prokaryotic viruses and accelerate the development of novel technologies based on these ubiquitous organisms.

  6. CRISPR/CAS9 based engineering of actinomycetal genomes

    DEFF Research Database (Denmark)

    2016-01-01

    The present invention relates to CRISPR/Cas-based methods for generating random-sized deletions around at least one target nucleic acid sequence, or for generating precise indels around at least one target nucleic acid sequence, or for modulating transcription of at least one target nucleic acid...

  7. Evolution and classification of the CRISPR-Cas systems

    NARCIS (Netherlands)

    Makarova, K.S.; Brouns, S.J.J.; Oost, van der J.

    2011-01-01

    The CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated proteins) modules are adaptive immunity systems that are present in many archaea and bacteria. These defence systems are encoded by operons that have an extraordinarily diverse architecture and a high rate of

  8. Research Needed on the Use of CAS Standards and Guidelines.

    Science.gov (United States)

    Creamer, Don G.

    2003-01-01

    This article suggests research projects that would extend the knowledge base about the use of Council for the Advancement of Standards in Higher Education (CAS) standards and guidelines in useful ways. Included are five research questions and specific research methodologies to guide researchers. (Contains 20 references.) (Author)

  9. Preparing Students to Take SOA/CAS Exam FM/2

    Science.gov (United States)

    Marchand, Richard J.

    2014-01-01

    This paper provides suggestions for preparing students to take the actuarial examination on financial mathematics, SOA/CAS Exam FM/2. It is based on current practices employed at Slippery Rock University, a small public liberal arts university. Detailed descriptions of our Theory of Interest course and subsequent Exam FM/2 prep course are provided…

  10. Can an Arthroplasty Registry Help Decrease Transfusions in Primary Total Joint Replacement? A Quality Initiative.

    Science.gov (United States)

    Markel, David C; Allen, Mark W; Zappa, Nicole M

    2016-01-01

    Standardized care plans are effective at controlling cost and quality. Registries provide insights into quality and outcomes for use of implants, but most registries do not combine implant and care quality data. In 2012, several Michigan area hospitals and a major insurance provider formed a voluntary statewide total joint database/registry, the Michigan Arthroplasty Registry Collaborative Quality Initiative (MARCQI), to collect procedural, hospital, discharge, and readmission data. Noting substantial variation in transfusion practices after total joint arthroplasty (TJA) in our institutions, we used these prospectively collected data to examine whether awareness and education of the American Association of Blood Banks' (AABB) transfusion guidelines would result in decreased transfusions. (1) Can an established arthroplasty registry help implement a quality initiative (QI) designed to decrease the proportion of transfused postoperative patients undergoing TJA? (2) Do data-driven transfusion protocols decrease length of stay without increasing ischemic complications (myocardial infarctions and cerebrovascular accidents)? (3) Are decreased transfusion proportions associated with decreased readmissions, nonischemic morbidity (including deep vein thrombosis and deep prosthetic infection), and mortality in postoperative patients who had undergone TJA? After reviewing data from the recently established MARCQI registry, the orthopaedic department noticed many discrepancies and practice variances regarding blood transfusions among their providers. In October 2013, a QI was implemented to raise awareness of the discrepancies and education about the AABB guidelines was presented at the monthly orthopaedic service line meeting. A total of 1872 TJA cases were reviewed; 50 were excluded for incomplete data and two for intraoperative transfusions for the period before education (May 2012 to June 2013, n = 1240) and after education (November 2013 to April 2014, n = 580). Data

  11. Spectral Time Series of the Cas A Supernova

    Science.gov (United States)

    Rest, Armin

    2016-10-01

    We propose to obtain time-resolved spectroscopy of the outburst of the enigmatic historical supernova Cas A using STIS spectroscopy of light scattered by a narrow filament of interstellar dust. Our group has identified recent, high-surface brightness filaments that are likely to provide high signal-to-noise reproduction of the evolving spectrum of the Cas A outburst using verified, published techniques developed by us.The timescales to see any appreciable evolution in individual astrophysical objects are typically many orders of magnitudes larger than a human life. As a result, astronomers study large numbers of objects at different stages of their evolution to connect how a single object should change with time. Cas A can provide us with the ability, to look back in time to the point of explosion by observing its light echoes - SN light scattered off of dust in the Milky Way, which causes a time delay in reaching us. In obtaining spectra of light echoes, we have been able to determine the maximum-light characteristics of the SN. Our goal here is to obtain a single STIS spectrum of a bright Cas A LE, which will provide us a time series of spectra and a spatially resolved light curve of the Cas A SN. With these data, we will measure the properties of the cooling envelope after the shock breakout of the SN to estimate the radius of the progenitor star. We will then be able to connect the progenitor star to the explosion to the SN to the SNR.

  12. SD-CAS: Spin Dynamics by Computer Algebra System.

    Science.gov (United States)

    Filip, Xenia; Filip, Claudiu

    2010-11-01

    A computer algebra tool for describing the Liouville-space quantum evolution of nuclear 1/2-spins is introduced and implemented within a computational framework named Spin Dynamics by Computer Algebra System (SD-CAS). A distinctive feature compared with numerical and previous computer algebra approaches to solving spin dynamics problems results from the fact that no matrix representation for spin operators is used in SD-CAS, which determines a full symbolic character to the performed computations. Spin correlations are stored in SD-CAS as four-entry nested lists of which size increases linearly with the number of spins into the system and are easily mapped into analytical expressions in terms of spin operator products. For the so defined SD-CAS spin correlations a set of specialized functions and procedures is introduced that are essential for implementing basic spin algebra operations, such as the spin operator products, commutators, and scalar products. They provide results in an abstract algebraic form: specific procedures to quantitatively evaluate such symbolic expressions with respect to the involved spin interaction parameters and experimental conditions are also discussed. Although the main focus in the present work is on laying the foundation for spin dynamics symbolic computation in NMR based on a non-matrix formalism, practical aspects are also considered throughout the theoretical development process. In particular, specific SD-CAS routines have been implemented using the YACAS computer algebra package (http://yacas.sourceforge.net), and their functionality was demonstrated on a few illustrative examples. Copyright © 2010 Elsevier Inc. All rights reserved.

  13. PinAPL-Py: A comprehensive web-application for the analysis of CRISPR/Cas9 screens.

    Science.gov (United States)

    Spahn, Philipp N; Bath, Tyler; Weiss, Ryan J; Kim, Jihoon; Esko, Jeffrey D; Lewis, Nathan E; Harismendy, Olivier

    2017-11-20

    Large-scale genetic screens using CRISPR/Cas9 technology have emerged as a major tool for functional genomics. With its increased popularity, experimental biologists frequently acquire large sequencing datasets for which they often do not have an easy analysis option. While a few bioinformatic tools have been developed for this purpose, their utility is still hindered either due to limited functionality or the requirement of bioinformatic expertise. To make sequencing data analysis of CRISPR/Cas9 screens more accessible to a wide range of scientists, we developed a Platform-independent Analysis of Pooled Screens using Python (PinAPL-Py), which is operated as an intuitive web-service. PinAPL-Py implements state-of-the-art tools and statistical models, assembled in a comprehensive workflow covering sequence quality control, automated sgRNA sequence extraction, alignment, sgRNA enrichment/depletion analysis and gene ranking. The workflow is set up to use a variety of popular sgRNA libraries as well as custom libraries that can be easily uploaded. Various analysis options are offered, suitable to analyze a large variety of CRISPR/Cas9 screening experiments. Analysis output includes ranked lists of sgRNAs and genes, and publication-ready plots. PinAPL-Py helps to advance genome-wide screening efforts by combining comprehensive functionality with user-friendly implementation. PinAPL-Py is freely accessible at http://pinapl-py.ucsd.edu with instructions and test datasets.

  14. A non-inheritable maternal Cas9-based multiple-gene editing system in mice

    OpenAIRE

    Takayuki Sakurai; Akiko Kamiyoshi; Hisaka Kawate; Chie Mori; Satoshi Watanabe; Megumu Tanaka; Ryuichi Uetake; Masahiro Sato; Takayuki Shindo

    2016-01-01

    The CRISPR/Cas9 system is capable of editing multiple genes through one-step zygote injection. The preexisting method is largely based on the co-injection of Cas9 DNA (or mRNA) and guide RNAs (gRNAs); however, it is unclear how many genes can be simultaneously edited by this method, and a reliable means to generate transgenic (Tg) animals with multiple gene editing has yet to be developed. Here, we employed non-inheritable maternal Cas9 (maCas9) protein derived from Tg mice with systemic Cas9...

  15. Production of genome-edited pluripotent stem cells and mice by CRISPR/Cas.

    Science.gov (United States)

    Horii, Takuro; Hatada, Izuho

    2016-01-01

    Clustered regularly at interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) nucleases, so-called CRISPR/Cas, was recently developed as an epoch-making genome engineering technology. This system only requires Cas9 nuclease and single-guide RNA complementary to a target locus. CRISPR/Cas enables the generation of knockout cells and animals in a single step. This system can also be used to generate multiple mutations and knockin in a single step, which is not possible using other methods. In this review, we provide an overview of genome editing by CRISPR/Cas in pluripotent stem cells and mice.

  16. European Registry of Carotid Artery Stenting: results from a prospective registry of eight high volume EUROPEAN institutions.

    Science.gov (United States)

    Stabile, Eugenio; Garg, Pallav; Cremonesi, Alberto; Bosiers, Marc; Reimers, Bernhard; Setacci, Carlo; Cao, Piergiorgio; Schmidt, Andrej; Sievert, Horst; Peeters, Patrick; Nikas, Dimitry; Werner, Martin; de Donato, Gianmarco; Parlani, Giambattista; Castriota, Fausto; Hornung, Marius; Mauri, Laura; Rubino, Paolo

    2012-08-01

    Carotid endarterectomy (CEA) is the standard revascularization therapy to prevent stroke in patients with carotid artery disease. Carotid artery stenting (CAS) could be considered a potential alternative in patients at high surgical risk. Recent clinical trials have challenged this concept due a relatively high incidence of post-CAS adverse events, which occurred in low volume centers. The aim of this study was to evaluate the outcomes associated with neuroprotected CAS in selected high volume centers. From January 2007 to December 2007, 1,611 patients underwent neuroprotected CAS in eight European Centers. For each patients, clinical, procedural, and one month follow-up data from all patients have been collected. An independent clinical events committee adjudicated the events. Overall in hospital death was 0.06% (one patient), whereas in-hospital stroke was 0.49% (eight patients). Between hospital discharge and 30 days three additional patients died (0.18%) and 10 patients experienced a stroke (0.67%). Overall 30 days mortality was 0.24% (four patients) and stroke incidence 1.12% (18 patients). The 30 day stroke/death rate was 1.36%. CAS is a reasonable alternative to CEA to treat carotid artery atherosclerosis in well-experienced high volume centers. These data suggest that future prospective trials comparing CAS and CEA outcomes should include only centers highly experienced in both treatment modalities. Copyright © 2012 Wiley Periodicals, Inc.

  17. All-in-One CRISPR-Cas9/FokI-dCas9 Vector-Mediated Multiplex Genome Engineering in Cultured Cells.

    Science.gov (United States)

    Sakuma, Tetsushi; Sakamoto, Takuya; Yamamoto, Takashi

    2017-01-01

    CRISPR-Cas9 enables highly convenient multiplex genome engineering in cultured cells, because it utilizes generic Cas9 nuclease and an easily customizable single-guide RNA (sgRNA) for site-specific DNA double-strand break induction. We previously established a multiplex CRISPR-Cas9 assembly system for constructing an all-in-one vector simultaneously expressing multiple sgRNAs and Cas9 nuclease or other Cas9 variants including FokI-dCas9, which supersedes the wild-type Cas9 with regard to high specificity. In this chapter, we describe a streamlined protocol to design and construct multiplex CRISPR-Cas9 or FokI-dCas9 vectors, to introduce them into cultured cells by lipofection or electroporation, to enrich the genomically edited cells with a transient puromycin selection, to validate the mutation efficiency by Surveyor nuclease assay, and to perform off-target analyses. We show that our protocol enables highly efficient multiplex genome engineering even in hard-to-transfect HepG2 cells.

  18. CasEMBLR: Cas9-Facilitated Multiloci Genomic Integration of in Vivo Assembled DNA Parts in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Jakociunas, Tadas; Rajkumar, Arun Stephen; Zhang, Jie

    2015-01-01

    , we present a method for marker-free multiloci integration of in vivo assembled DNA parts. By the use of CRISPR/Cas9-mediated one-step double-strand breaks at single, double and triple integration sites we report the successful in vivo assembly and chromosomal integration of DNA parts. We call our...

  19. The Danish National Multiple Myeloma Registry

    DEFF Research Database (Denmark)

    Gimsing, Peter; Holmström, Morten Orebo; Klausen, Tobias Wirenfelt

    2016-01-01

    AIM: The Danish National Multiple Myeloma Registry (DMMR) is a population-based clinical quality database established in January 2005. The primary aim of the database is to ensure that diagnosis and treatment of plasma cell dyscrasia are of uniform quality throughout the country. Another aim...... diagnosed patients with multiple myeloma (MM), smoldering MM, solitary plasmacytomas, and plasma cell leukemia in Denmark are registered annually; ~350 patients. Amyloid light-chain amyloidosis, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome......), monoclonal gammopathy of undetermined significance and monoclonal gammopathy of undetermined significance with polyneuropathy have been registered since 2014. MAIN VARIABLES: The main registered variables at diagnosis are patient demographics, baseline disease characteristics, myeloma-defining events...

  20. The Danish Registry of Diabetic Retinopathy

    DEFF Research Database (Denmark)

    Andersen, Nis; Hjortdal, Jesper Østergaard; Schielke, Katja Christina

    2016-01-01

    . Denmark (5.5 million inhabitants) has ~320,000 diabetes patients with an annual increase of 27,000 newly diagnosed patients. The Danish Registry of Diabetic Retinopathy (DiaBase) collects data on all diabetes patients aged ≥18 years who attend screening for diabetic eye disease in hospital eye departments...... and in private ophthalmological practice. In 2014-2015, DiaBase included data collected from 77,968 diabetes patients. Main variables: The main variables provide data for calculation of performance indicators to monitor the quality of diabetic eye screening and development of diabetic retinopathy. Data...... with respect to age, sex, best corrected visual acuity, screening frequency, grading of diabetic retinopathy and maculopathy at each visit, progression/regression of diabetic eye disease, and prevalence of blindness were obtained. Data analysis from DiaBase’s latest annual report (2014-2015) indicates...

  1. Danish Registry of Childhood and Adolescent Diabetes

    DEFF Research Database (Denmark)

    Svensson, Jannet; Cerqueira, Charlotte; Kjærsgaard, Per

    2016-01-01

    children diagnosed with diabetes before the age of 15 years since 1996. Since 2015, every child followed up at a pediatric center (years of age) will be included. MAIN VARIABLES: The variables in the registry are the quality indicators, demographic variables, associated conditions, diabetes......, neuropathy, number of severe hypoglycemic events, and hospitalization with ketoacidosis. DESCRIPTIVE DATA: The number of children diagnosed with diabetes is increasing with ∼3% per year mainly for type 1 diabetes (ie, 296 new patients years of age were diagnosed in 2014). The disease management has...... classification, family history of diabetes, growth parameters, self-care, and treatment variables. The quality indicators are selected based on international consensus of measures of good clinical practice. The indicators are metabolic control as assessed by HbA1c, blood pressure, albuminuria, retinopathy...

  2. The Danish Registry of Diabetic Retinopathy

    DEFF Research Database (Denmark)

    Andersen, Nis; Hjortdal, Jesper Østergaard; Schielke, Katja Christina

    2016-01-01

    . Denmark (5.5 million inhabitants) has ~320,000 diabetes patients with an annual increase of 27,000 newly diagnosed patients. The Danish Registry of Diabetic Retinopathy (DiaBase) collects data on all diabetes patients aged ≥18 years who attend screening for diabetic eye disease in hospital eye departments...... and in private ophthalmological practice. In 2014-2015, DiaBase included data collected from 77,968 diabetes patients. MAIN VARIABLES: The main variables provide data for calculation of performance indicators to monitor the quality of diabetic eye screening and development of diabetic retinopathy. Data...... with respect to age, sex, best corrected visual acuity, screening frequency, grading of diabetic retinopathy and maculopathy at each visit, progression/regression of diabetic eye disease, and prevalence of blindness were obtained. Data analysis from DiaBase's latest annual report (2014-2015) indicates...

  3. The Corrona US registry of rheumatic and autoimmune diseases.

    Science.gov (United States)

    Kremer, Joel M

    2016-01-01

    The Corrona US national registry collects data concerning patient status from both the rheumatologist and patient at routine clinical encounters. Corrona has functioning disease registries in rheumatoid arthritis, psoriatic arthritis, spondyloarthropathies, psoriasis and inflammatory bowel disease. Corrona merges data concerning long-term effectiveness and safety, as well as comparative and cost effectiveness of agents to treat these autoimmune diseases.

  4. Data quality in the Danish National Acute Leukemia Registry

    DEFF Research Database (Denmark)

    Ostgård, Lene Sofie Granfeldt; Nørgaard, Jan Maxwell; Severinsen, Marianne Tang

    2013-01-01

    The Danish National Acute Leukemia Registry (DNLR) has documented coverage of above 98.5%. Less is known about the quality of the recorded data.......The Danish National Acute Leukemia Registry (DNLR) has documented coverage of above 98.5%. Less is known about the quality of the recorded data....

  5. Paper 6: EUROCAT member registries: organization and activities

    DEFF Research Database (Denmark)

    Greenlees, Ruth; Neville, Amanda; Addor, Marie-Claude

    2011-01-01

    EUROCAT is a network of population-based congenital anomaly registries providing standardized epidemiologic information on congenital anomalies in Europe. There are three types of EUROCAT membership: full, associate, or affiliate. Full member registries send individual records of all congenital a...

  6. Cancer incidence in Morocco: report from Casablanca registry 2005 ...

    African Journals Online (AJOL)

    Introduction: Few population-based cancer registries are in place in developing countries. In order to know the burden of cancer in Moroccan population, cancer registry initiative was put in place in the Casablanca district, the biggest city of Morocco. Methods: The data collected covers 3.6 millions inhabitant and included ...

  7. 37 CFR 201.25 - Visual Arts Registry.

    Science.gov (United States)

    2010-07-01

    ... the copyright law. Visual Arts Registry Statements which are illegible or fall outside of the scope of... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Visual Arts Registry. 201.25 Section 201.25 Patents, Trademarks, and Copyrights COPYRIGHT OFFICE, LIBRARY OF CONGRESS COPYRIGHT OFFICE...

  8. Development of the SIOPE DIPG network, registry and imaging repository

    DEFF Research Database (Denmark)

    Veldhuijzen van Zanten, Sophie E M; Baugh, Joshua; Chaney, Brooklyn

    2017-01-01

    was developed, The SIOPE DIPG Registry and Imaging Repository, to centrally collect data of DIPG patients. As for April 2016, clinical data as well as MR-scans of 694 patients have been entered into the SIOPE DIPG Registry/Imaging Repository. The median progression free survival is 6.0 months (95% Confidence...

  9. Versatile High-Throughput Fluorescence Assay for Monitoring Cas9 Activity.

    Science.gov (United States)

    Seamon, Kyle J; Light, Yooli K; Saada, Edwin A; Schoeniger, Joseph S; Harmon, Brooke

    2018-06-05

    The RNA-guided DNA nuclease Cas9 is now widely used for the targeted modification of genomes of human cells and various organisms. Despite the extensive use of Clustered Regularly Interspaced Palindromic Repeats (CRISPR) systems for genome engineering and the rapid discovery and engineering of new CRISPR-associated nucleases, there are no high-throughput assays for measuring enzymatic activity. The current laboratory and future therapeutic uses of CRISPR technology have a significant risk of accidental exposure or clinical off-target effects, underscoring the need for therapeutically effective inhibitors of Cas9. Here, we develop a fluorescence assay for monitoring Cas9 nuclease activity and demonstrate its utility with S. pyogenes (Spy), S. aureus (Sau), and C. jejuni (Cje) Cas9. The assay was validated by quantitatively profiling the species specificity of published anti-CRISPR (Acr) proteins, confirming the reported inhibition of Spy Cas9 by AcrIIA4 and Cje Cas9 by AcrIIC1 and no inhibition of Sau Cas9 by either anti-CRISPR. To identify drug-like inhibitors, we performed a screen of 189 606 small molecules for inhibition of Spy Cas9. Of 437 hits (0.2% hit rate), six were confirmed as Cas9 inhibitors in a direct gel electrophoresis secondary assay. The high-throughput nature of this assay makes it broadly applicable for the discovery of additional Cas9 inhibitors or the characterization of Cas9 enzyme variants.

  10. Cas9, Cpf1 and C2c1/2/3-What's next?

    Science.gov (United States)

    Nakade, Shota; Yamamoto, Takashi; Sakuma, Tetsushi

    2017-05-04

    Since the rapid emergence of clustered regulatory interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) system, developed as a genome engineering tool in 2012-2013, most researchers in the life science field have had a fixated interest in this fascinating technology. CRISPR-Cas9 is an RNA-guided DNA endonuclease system, which consists of Cas9 nuclease defining a few targeting base via protospacer adjacent motif complexed with easily customizable single guide RNA targeting around 20-bp genomic sequence. Although Streptococcus pyogenes Cas9 (SpCas9), one of the Cas9 proteins that applications in genome engineering were first demonstrated, still has wide usage because of its high nuclease activity and broad targeting range, there are several limitations such as large molecular weight and potential off-target effect. In this commentary, we describe various improvements and alternatives of CRISPR-Cas systems, including engineered Cas9 variants, Cas9 homologs, and novel Cas proteins other than Cas9. These variations enable flexible genome engineering with high efficiency and specificity, orthogonal genetic control at multiple gene loci, gene knockdown, or fluorescence imaging of transcripts mediated by RNA targeting, and beyond.

  11. The Revolution Continues: Newly Discovered Systems Expand the CRISPR-Cas Toolkit.

    Science.gov (United States)

    Murugan, Karthik; Babu, Kesavan; Sundaresan, Ramya; Rajan, Rakhi; Sashital, Dipali G

    2017-10-05

    CRISPR-Cas systems defend prokaryotes against bacteriophages and mobile genetic elements and serve as the basis for revolutionary tools for genetic engineering. Class 2 CRISPR-Cas systems use single Cas endonucleases paired with guide RNAs to cleave complementary nucleic acid targets, enabling programmable sequence-specific targeting with minimal machinery. Recent discoveries of previously unidentified CRISPR-Cas systems have uncovered a deep reservoir of potential biotechnological tools beyond the well-characterized Type II Cas9 systems. Here we review the current mechanistic understanding of newly discovered single-protein Cas endonucleases. Comparison of these Cas effectors reveals substantial mechanistic diversity, underscoring the phylogenetic divergence of related CRISPR-Cas systems. This diversity has enabled further expansion of CRISPR-Cas biotechnological toolkits, with wide-ranging applications from genome editing to diagnostic tools based on various Cas endonuclease activities. These advances highlight the exciting prospects for future tools based on the continually expanding set of CRISPR-Cas systems. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Structural Basis for the Altered PAM Specificities of Engineered CRISPR-Cas9.

    Science.gov (United States)

    Hirano, Seiichi; Nishimasu, Hiroshi; Ishitani, Ryuichiro; Nureki, Osamu

    2016-03-17

    The RNA-guided endonuclease Cas9 cleaves double-stranded DNA targets bearing a PAM (protospacer adjacent motif) and complementarity to the guide RNA. A recent study showed that, whereas wild-type Streptococcus pyogenes Cas9 (SpCas9) recognizes the 5'-NGG-3' PAM, the engineered VQR, EQR, and VRER SpCas9 variants recognize the 5'-NGA-3', 5'-NGAG-3', and 5'-NGCG-3' PAMs, respectively, thus expanding the targetable sequences in Cas9-mediated genome editing applications. Here, we present the high-resolution crystal structures of the three SpCas9 variants in complexes with a single-guide RNA and its altered PAM-containing, partially double-stranded DNA targets. A structural comparison of the three SpCas9 variants with wild-type SpCas9 revealed that the multiple mutations synergistically induce an unexpected displacement in the phosphodiester backbone of the PAM duplex, thereby allowing the SpCas9 variants to directly recognize the altered PAM nucleotides. Our findings explain the altered PAM specificities of the SpCas9 variants and establish a framework for further rational engineering of CRISPR-Cas9. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Evolved Cas9 variants with broad PAM compatibility and high DNA specificity.

    Science.gov (United States)

    Hu, Johnny H; Miller, Shannon M; Geurts, Maarten H; Tang, Weixin; Chen, Liwei; Sun, Ning; Zeina, Christina M; Gao, Xue; Rees, Holly A; Lin, Zhi; Liu, David R

    2018-04-05

    A key limitation of the use of the CRISPR-Cas9 system for genome editing and other applications is the requirement that a protospacer adjacent motif (PAM) be present at the target site. For the most commonly used Cas9 from Streptococcus pyogenes (SpCas9), the required PAM sequence is NGG. No natural or engineered Cas9 variants that have been shown to function efficiently in mammalian cells offer a PAM less restrictive than NGG. Here we use phage-assisted continuous evolution to evolve an expanded PAM SpCas9 variant (xCas9) that can recognize a broad range of PAM sequences including NG, GAA and GAT. The PAM compatibility of xCas9 is the broadest reported, to our knowledge, among Cas9 proteins that are active in mammalian cells, and supports applications in human cells including targeted transcriptional activation, nuclease-mediated gene disruption, and cytidine and adenine base editing. Notably, despite its broadened PAM compatibility, xCas9 has much greater DNA specificity than SpCas9, with substantially lower genome-wide off-target activity at all NGG target sites tested, as well as minimal off-target activity when targeting genomic sites with non-NGG PAMs. These findings expand the DNA targeting scope of CRISPR systems and establish that there is no necessary trade-off between Cas9 editing efficiency, PAM compatibility and DNA specificity.

  14. I RBH - First Brazilian Hypertension Registry.

    Science.gov (United States)

    Jardim, Paulo César Brandão Veiga; Souza, Weimar Kunz Sebba Barroso de; Lopes, Renato Delascio; Brandão, Andréa Araújo; Malachias, Marcus V Bolívar; Gomes, Marco Mota; Moreno Júnior, Heitor; Barbosa, Eduardo Costa Duarte; Póvoa, Rui Manoel Dos Santos

    2016-08-01

    A registry assessing the care of hypertensive patients in daily clinical practice in public and private centers in various Brazilian regions has not been conducted to date. Such analysis is important to elucidate the effectiveness of this care. To document the current clinical practice for the treatment of hypertension with identification of the profile of requested tests, type of administered treatment, level of blood pressure (BP) control, and adherence to treatment. National, observational, prospective, and multicenter study that will include patients older than 18 years with hypertension for at least 4 weeks, following up in public and private centers and after signing a consent form. The study will exclude patients undergoing dialysis, hospitalized in the previous 30 days, with class III or IV heart failure, pregnant or nursing, with severe liver disease, stroke or acute myocardial infarction in the past 30 days, or with diseases with a survival prognosis crisis, cardiocirculatory events, and cardiovascular death, while secondary outcomes will be hospitalization for heart failure and requirement of dialysis. A subgroup analysis of 15% of the sample will include noninvasive central pressure evaluation at baseline and study end. The estimated sample size is 3,000 individuals for a prevalence of 5%, sample error of 2%, and 95% confidence interval. The results will be presented after the final evaluation, which will occur at the end of a 1-year follow-up. The analysis of this registry will improve the knowledge and optimize the treatment of hypertension in Brazil, as a way of modifying the prognosis of cardiovascular disease in the country.

  15. Chemical and Biophysical Modulation of Cas9 for Tunable Genome Engineering.

    Science.gov (United States)

    Nuñez, James K; Harrington, Lucas B; Doudna, Jennifer A

    2016-03-18

    The application of the CRISPR-Cas9 system for genome engineering has revolutionized the ability to interrogate genomes of mammalian cells. Programming the Cas9 endonuclease to induce DNA breaks at specified sites is achieved by simply modifying the sequence of its cognate guide RNA. Although Cas9-mediated genome editing has been shown to be highly specific, cleavage events at off-target sites have also been reported. Minimizing, and eventually abolishing, unwanted off-target cleavage remains a major goal of the CRISPR-Cas9 technology before its implementation for therapeutic use. Recent efforts have turned to chemical biology and biophysical approaches to engineer inducible genome editing systems for controlling Cas9 activity at the transcriptional and protein levels. Here, we review recent advancements to modulate Cas9-mediated genome editing by engineering split-Cas9 constructs, inteins, small molecules, protein-based dimerizing domains, and light-inducible systems.

  16. Methods for decoding Cas9 protospacer adjacent motif (PAM) sequences: A brief overview.

    Science.gov (United States)

    Karvelis, Tautvydas; Gasiunas, Giedrius; Siksnys, Virginijus

    2017-05-15

    Recently the Cas9, an RNA guided DNA endonuclease, emerged as a powerful tool for targeted genome manipulations. Cas9 protein can be reprogrammed to cleave, bind or nick any DNA target by simply changing crRNA sequence, however a short nucleotide sequence, termed PAM, is required to initiate crRNA hybridization to the DNA target. PAM sequence is recognized by Cas9 protein and must be determined experimentally for each Cas9 variant. Exploration of Cas9 orthologs could offer a diversity of PAM sequences and novel biochemical properties that may be beneficial for genome editing applications. Here we briefly review and compare Cas9 PAM identification assays that can be adopted for other PAM-dependent CRISPR-Cas systems. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Advantages and limitations of national arthroplasty registries. The need for multicenter registries: the Rempro-SBQ

    Directory of Open Access Journals (Sweden)

    Luiz Sérgio Marcelino Gomes

    Full Text Available Abstract While the value of national arthroplasty registries (NAR for quality improvement in total hip arthroplasty (THA has already been widely reported, some methodological limitations associated with observational epidemiological studies that may interfere with the assessment of safety and efficacy of prosthetic implants have recently been described in the literature. Among the main limitations of NAR, the need for at least 80% compliance of all health institutions covered by the registry is emphasized; completeness equal or greater than 90% of all THA performed; restricted data collection; use of revision surgery as the sole criterion for outcome; and the inability of establishing a definite causal link with prosthetic dysfunction. The present article evaluates the advantages and limitations of NAR, in the light of current knowledge, which point to the need for a broader data collection and the use of more structured criteria for defining outcomes. In this scenario, the authors describe of idealization, conceptual and operational structure, and the project of implantation and implementation of a multicenter registry model, called Rempro-SBQ, which includes healthcare institutions already linked to the Brazilian Hip Society (Sociedade Brasileira de Quadril [SBQ]. This partnership enables the collection of more reliable and comprehensive data at a higher hierarchical level, with a significant reduction in maintenance and financing costs. The quality improvement actions supported by SBQ may enhance its effectiveness and stimulate greater adherence for collecting, storing, interpreting, and disseminating information (feedback.

  18. Advantages and limitations of national arthroplasty registries. The need for multicenter registries: the Rempro-SBQ.

    Science.gov (United States)

    Gomes, Luiz Sérgio Marcelino; Roos, Milton Valdomiro; Takata, Edmilson Takehiro; Schuroff, Ademir Antônio; Alves, Sérgio Delmonte; Camisa Júnior, Antero; Miranda, Ricardo Horta

    2017-01-01

    While the value of national arthroplasty registries (NAR) for quality improvement in total hip arthroplasty (THA) has already been widely reported, some methodological limitations associated with observational epidemiological studies that may interfere with the assessment of safety and efficacy of prosthetic implants have recently been described in the literature. Among the main limitations of NAR, the need for at least 80% compliance of all health institutions covered by the registry is emphasized; completeness equal or greater than 90% of all THA performed; restricted data collection; use of revision surgery as the sole criterion for outcome; and the inability of establishing a definite causal link with prosthetic dysfunction. The present article evaluates the advantages and limitations of NAR, in the light of current knowledge, which point to the need for a broader data collection and the use of more structured criteria for defining outcomes. In this scenario, the authors describe of idealization, conceptual and operational structure, and the project of implantation and implementation of a multicenter registry model, called Rempro-SBQ, which includes healthcare institutions already linked to the Brazilian Hip Society (Sociedade Brasileira de Quadril [SBQ]). This partnership enables the collection of more reliable and comprehensive data at a higher hierarchical level, with a significant reduction in maintenance and financing costs. The quality improvement actions supported by SBQ may enhance its effectiveness and stimulate greater adherence for collecting, storing, interpreting, and disseminating information (feedback).

  19. Rationale and design of a large registry on renal denervation: the Global SYMPLICITY registry.

    Science.gov (United States)

    Böhm, Michael; Mahfoud, Felix; Ukena, Christian; Bauer, Axel; Fleck, Eckart; Hoppe, Uta C; Kintscher, Ulrich; Narkiewicz, Krzysztof; Negoita, Manuela; Ruilope, Luis; Rump, L Christian; Schlaich, Markus; Schmieder, Roland; Sievert, Horst; Weil, Joachim; Williams, Bryan; Zeymer, Uwe; Mancia, Giuseppe

    2013-08-22

    Hypertension is a global healthcare concern associated with a wide range of comorbidities. The recognition that elevated sympathetic drive plays an important role in the pathogenesis of hypertension led to the use of renal artery denervation to interrupt the efferent and afferent sympathetic nerves between the brain and kidneys to lower blood pressure. Clinical trials of the Symplicity™ renal denervation system have demonstrated that radiofrequency ablation of renal artery nerves is safe and significantly lowers blood pressure in patients with severe resistant (systolic BP >160 mmHg) hypertension. Smaller ancillary studies in hypertensive patients suggest a benefit from renal denervation in a variety of conditions such as chronic kidney disease, glucose intolerance, sleep apnoea and heart failure. The Global SYMPLICITY registry, which incorporates the GREAT SYMPLICITY registry initiated in Germany, is being conducted worldwide to evaluate the safety and efficacy of treatment with the Symplicity renal denervation system in real-world uncontrolled hypertensive patients, looking first at subjects with severe resistant hypertension to confirm the results of prior clinical trials, but then also subjects with a wider range of baseline blood pressure and coexisting comorbidities. The rationale, design and first baseline data from the Global SYMPLICITY registry are presented.

  20. Rapid and tunable method to temporally control gene editing based on conditional Cas9 stabilization. | Office of Cancer Genomics

    Science.gov (United States)

    The CRISPR/Cas9 system is a powerful tool for studying gene function. Here, we describe a method that allows temporal control of CRISPR/Cas9 activity based on conditional Cas9 destabilization. We demonstrate that fusing an FKBP12-derived destabilizing domain to Cas9 (DD-Cas9) enables conditional Cas9 expression and temporal control of gene editing in the presence of an FKBP12 synthetic ligand. This system can be easily adapted to co-express, from the same promoter, DD-Cas9 with any other gene of interest without co-modulation of the latter.

  1. Limitations of drug registries to evaluate orphan medicinal products for the treatment of lysosomal storage disorders

    NARCIS (Netherlands)

    Hollak, Carla E. M.; Aerts, Johannes M. F. G.; Aymé, Ségolène; Manuel, Jeremy

    2011-01-01

    Orphan drugs are often approved under exceptional circumstances, requiring submission of additional data on safety and effectiveness through registries. These registries are mainly focused on one drug only and data is frequently incomplete. Some registries also address phenotypic heterogeneity and

  2. Insights into the CRISPR/Cas system of Gardnerella vaginalis

    Directory of Open Access Journals (Sweden)

    Pleckaityte Milda

    2012-12-01

    Full Text Available Abstract Background Gardnerella vaginalis is identified as the predominant colonist of the vaginal tracts of women diagnosed with bacterial vaginosis (BV. G. vaginalis can be isolated from healthy women, and an asymptomatic BV state is also recognised. The association of G. vaginalis with different clinical phenotypes could be explained by different cytotoxicity of the strains, presumably based on disparate gene content. The contribution of horizontal gene transfer to shaping the genomes of G. vaginalis is acknowledged. The CRISPR loci of the recently discovered CRISPR/Cas microbial defence system provide a historical view of the exposure of prokaryotes to a variety of foreign genetic elements. Results The CRISPR/Cas loci were analysed using available sequence data from three G. vaginalis complete genomes and 18 G. vaginalis draft genomes in the NCBI database, as well as PCR amplicons of the genomic DNA of 17 clinical isolates. The cas genes in the CRISPR/Cas loci of G. vaginalis belong to the E. coli subtype. Approximately 20% of the spacers had matches in the GenBank database. Sequence analysis of the CRISPR arrays revealed that nearly half of the spacers matched G. vaginalis chromosomal sequences. The spacers that matched G. vaginalis chromosomal sequences were determined to not be self-targeting and were presumably neither constituents of mobile-element-associated genes nor derived from plasmids/viruses. The protospacers targeted by these spacers displayed conserved protospacer-adjacent motifs. Conclusions The CRISPR/Cas system has been identified in about one half of the analysed G. vaginalis strains. Our analysis of CRISPR sequences did not reveal a potential link between their presence and the virulence of the G. vaginalis strains. Based on the origins of the spacers found in the G. vaginalis CRISPR arrays, we hypothesise that the transfer of genetic material among G. vaginalis strains could be regulated by the CRISPR/Cas mechanism. The

  3. Chromosomal Targeting by the Type III-A CRISPR-Cas System Can Reshape Genomes in Staphylococcus aureus

    OpenAIRE

    Guan, Jing; Wang, Wanying; Sun, Baolin

    2017-01-01

    ABSTRACT CRISPR-Cas (clustered regularly interspaced short palindromic repeat [CRISPR]-CRISPR-associated protein [Cas]) systems can provide protection against invading genetic elements by using CRISPR RNAs (crRNAs) as a guide to locate and degrade the target DNA. CRISPR-Cas systems have been classified into two classes and five types according to the content of cas genes. Previous studies have indicated that CRISPR-Cas systems can avoid viral infection and block plasmid transfer. Here we show...

  4. Glocal clinical registries: pacemaker registry design and implementation for global and local integration--methodology and case study.

    Directory of Open Access Journals (Sweden)

    Kátia Regina da Silva

    Full Text Available The ability to apply standard and interoperable solutions for implementing and managing medical registries as well as aggregate, reproduce, and access data sets from legacy formats and platforms to advanced standard formats and operating systems are crucial for both clinical healthcare and biomedical research settings.Our study describes a reproducible, highly scalable, standard framework for a device registry implementation addressing both local data quality components and global linking problems.We developed a device registry framework involving the following steps: (1 Data standards definition and representation of the research workflow, (2 Development of electronic case report forms using REDCap (Research Electronic Data Capture, (3 Data collection according to the clinical research workflow and, (4 Data augmentation by enriching the registry database with local electronic health records, governmental database and linked open data collections, (5 Data quality control and (6 Data dissemination through the registry Web site. Our registry adopted all applicable standardized data elements proposed by American College Cardiology / American Heart Association Clinical Data Standards, as well as variables derived from cardiac devices randomized trials and Clinical Data Interchange Standards Consortium. Local interoperability was performed between REDCap and data derived from Electronic Health Record system. The original data set was also augmented by incorporating the reimbursed values paid by the Brazilian government during a hospitalization for pacemaker implantation. By linking our registry to the open data collection repository Linked Clinical Trials (LinkedCT we found 130 clinical trials which are potentially correlated with our pacemaker registry.This study demonstrates how standard and reproducible solutions can be applied in the implementation of medical registries to constitute a re-usable framework. Such approach has the potential to

  5. Glocal Clinical Registries: Pacemaker Registry Design and Implementation for Global and Local Integration – Methodology and Case Study

    Science.gov (United States)

    da Silva, Kátia Regina; Costa, Roberto; Crevelari, Elizabeth Sartori; Lacerda, Marianna Sobral; de Moraes Albertini, Caio Marcos; Filho, Martino Martinelli; Santana, José Eduardo; Vissoci, João Ricardo Nickenig; Pietrobon, Ricardo; Barros, Jacson V.

    2013-01-01

    Background The ability to apply standard and interoperable solutions for implementing and managing medical registries as well as aggregate, reproduce, and access data sets from legacy formats and platforms to advanced standard formats and operating systems are crucial for both clinical healthcare and biomedical research settings. Purpose Our study describes a reproducible, highly scalable, standard framework for a device registry implementation addressing both local data quality components and global linking problems. Methods and Results We developed a device registry framework involving the following steps: (1) Data standards definition and representation of the research workflow, (2) Development of electronic case report forms using REDCap (Research Electronic Data Capture), (3) Data collection according to the clinical research workflow and, (4) Data augmentation by enriching the registry database with local electronic health records, governmental database and linked open data collections, (5) Data quality control and (6) Data dissemination through the registry Web site. Our registry adopted all applicable standardized data elements proposed by American College Cardiology / American Heart Association Clinical Data Standards, as well as variables derived from cardiac devices randomized trials and Clinical Data Interchange Standards Consortium. Local interoperability was performed between REDCap and data derived from Electronic Health Record system. The original data set was also augmented by incorporating the reimbursed values paid by the Brazilian government during a hospitalization for pacemaker implantation. By linking our registry to the open data collection repository Linked Clinical Trials (LinkedCT) we found 130 clinical trials which are potentially correlated with our pacemaker registry. Conclusion This study demonstrates how standard and reproducible solutions can be applied in the implementation of medical registries to constitute a re-usable framework

  6. CRISPR-cas loci profiling of Cronobacter sakazakii pathovars.

    Science.gov (United States)

    Ogrodzki, Pauline; Forsythe, Stephen James

    2016-12-01

    Cronobacter sakazakii sequence types 1, 4, 8 and 12 are associated with outbreaks of neonatal meningitis and necrotizing enterocolitis infections. However clonality results in strains which are indistinguishable using conventional methods. This study investigated the use of clustered regularly interspaced short palindromic repeats (CRISPR)-cas loci profiling for epidemiological investigations. Seventy whole genomes of C. sakazakii strains from four clonal complexes which were widely distributed temporally, geographically and origin of source were profiled. All strains encoded the same type I-E subtype CRISPR-cas system with a total of 12 different CRISPR spacer arrays. This study demonstrated the greater discriminatory power of CRISPR spacer array profiling compared with multilocus sequence typing, which will be of use in source attribution during Cronobacter outbreak investigations.

  7. CRISPR/Cas-Mediated Knockin in Human Pluripotent Stem Cells.

    Science.gov (United States)

    Verma, Nipun; Zhu, Zengrong; Huangfu, Danwei

    2017-01-01

    Fluorescent reporter and epitope-tagged human pluripotent stem cells (hPSCs) greatly facilitate studies on the pluripotency and differentiation characteristics of these cells. Unfortunately traditional procedures to generate such lines are hampered by a low targeting efficiency that necessitates a lengthy process of selection followed by the removal of the selection cassette. Here we describe a procedure to generate fluorescent reporter and epitope tagged hPSCs in an efficient one-step process using the CRISPR/Cas technology. Although the method described uses our recently developed iCRISPR platform, the protocols can be adapted for general use with CRISPR/Cas or other engineered nucleases. The transfection procedures described could also be used for additional applications, such as overexpression or lineage tracing studies.

  8. CRISPR-Cas adaptive immune systems of the sulfolobales

    DEFF Research Database (Denmark)

    Garrett, Roger Antony; Shah, Shiraz Ali; Erdmann, Susanne

    2015-01-01

    The Sulfolobales have provided good model organisms for studying CRISPR-Cas systems of the crenarchaeal kingdom of the archaea. These organisms are infected by a wide range of exceptional archaea-specific viruses and conjugative plasmids, and their CRISPR-Cas systems generally exhibit extensive...... structural and functional diversity. They carry large and multiple CRISPR loci and often multiple copies of diverse Type I and Type III interference modules as well as more homogeneous adaptation modules. These acidothermophilic organisms have recently provided seminal insights into both the adaptation...... process, the diverse modes of interference, and their modes of regulation. The functions of the adaptation and interference modules tend to be loosely coupled and the stringency of the crRNA-DNA sequence matching during DNA interference is relatively low, in contrast to some more streamlined CRISPR...

  9. Application of CRISPR/Cas9 Technology to HBV

    Directory of Open Access Journals (Sweden)

    Guigao Lin

    2015-11-01

    Full Text Available More than 240 million people around the world are chronically infected with hepatitis B virus (HBV. Nucleos(tide analogs and interferon are the only two families of drugs to treat HBV currently. However, none of these anti-virals directly target the stable nuclear covalently closed circular DNA (cccDNA, which acts as a transcription template for viral mRNA and pre-genomic RNA synthesis and secures virus persistence. Thus, the fact that only a small number of patients treated achieve sustained viral response (SVR or cure, highlights the need for new therapies against HBV. The clustered regularly interspaced short palindromic repeats (CRISPR/Cas9 gene editing system can specifically target the conserved regions of the HBV genome. This results in robust viral suppression and provides a promising tool for eradicating the virus. In this review, we discuss the function and application of the CRISPR/Cas9 system as a novel therapy for HBV.

  10. CRISPR-Cas9 Toolkit for Actinomycete Genome Editing

    DEFF Research Database (Denmark)

    Tong, Yaojun; Robertsen, Helene Lunde; Blin, Kai

    2018-01-01

    engineering approaches for boosting known and discovering novel natural products. In order to facilitate the genome editing for actinomycetes, we developed a CRISPR-Cas9 toolkit with high efficiency for actinomyces genome editing. This basic toolkit includes a software for spacer (sgRNA) identification......, a system for in-frame gene/gene cluster knockout, a system for gene loss-of-function study, a system for generating a random size deletion library, and a system for gene knockdown. For the latter, a uracil-specific excision reagent (USER) cloning technology was adapted to simplify the CRISPR vector...... construction process. The application of this toolkit was successfully demonstrated by perturbation of genomes of Streptomyces coelicolor A3(2) and Streptomyces collinus Tü 365. The CRISPR-Cas9 toolkit and related protocol described here can be widely used for metabolic engineering of actinomycetes....

  11. CAS - CERN Accelerator School: Course on Digital Signal Processing

    CERN Document Server

    Digital Signal Processing; CAS 2007

    2008-01-01

    These proceedings present the lectures given at the twenty-first specialized course organized by the CERN Accelerator School (CAS), the topic being Digital Signal Processing. The course was held in Sigtuna, Sweden, from 31 May–9 June 2007. This is the first time this topic has been selected for a specialized course. Taking into account the number of related applications currently in use in accelerators around the world, it was recognized that such a topic should definitively be incorporated into the CAS series of specialized courses. The specific aim of the course was to introduce the participants to the use and programming of Digital Signal Processors (DSPs) and Field Programmable Gate Arrays (FPGAs) evaluation boards. The course consisted of lectures in the mornings covering fundamental background knowledge in mathematics, controls theory, design tools, programming hardware platforms, and implementation details. In the afternoons the students split into two groups with people working in pairs. One group w...

  12. CAS - CERN Accelerator School: Specialised course on Magnets

    CERN Document Server

    CAS 2009

    2010-01-01

    These proceedings present the lectures given at the twenty-third specialized course organized by the CERN Accelerator School (CAS), the topic being 'Magnets'. The course was held in Bruges, Belgium, from 16 to 25 June 2009. This is the first time this topic has been selected for a specialized course. Taking into account the number of related applications currently in use in accelerators around the world, but, even more important, the worrying decrease in the corresponding expertise in the different laboratories, it was recognized that such a topic should definitively be incorporated into the CAS series of specialized courses. The specific aim of the course was to introduce the participants to the basics of resistive magnet design and its underlying theoretical concepts. The first part of the school dealt with basic introductory courses such as Maxwell's equations for magnets, beam optics, physics and measurement of magnetic materials, the different types of resistive magnets and their respective performance, ...

  13. A Scalable Framework and Prototype for CAS e-Science

    Directory of Open Access Journals (Sweden)

    Yuanchun Zhou

    2007-07-01

    Full Text Available Based on the Small-World model of CAS e-Science and the power low of Internet, this paper presents a scalable CAS e-Science Grid framework based on virtual region called Virtual Region Grid Framework (VRGF. VRGF takes virtual region and layer as logic manage-unit. In VRGF, the mode of intra-virtual region is pure P2P, and the model of inter-virtual region is centralized. Therefore, VRGF is decentralized framework with some P2P properties. Further more, VRGF is able to achieve satisfactory performance on resource organizing and locating at a small cost, and is well adapted to the complicated and dynamic features of scientific collaborations. We have implemented a demonstration VRGF based Grid prototype—SDG.

  14. The Danish National Chronic Myeloid Neoplasia Registry

    Directory of Open Access Journals (Sweden)

    Bak M

    2016-10-01

    Full Text Available Marie Bak,1 Else Helene Ibfelt,2 Thomas Stauffer Larsen,3 Dorthe Rønnov-Jessen,4 Niels Pallisgaard,5 Ann Madelung,6 Lene Udby,1 Hans Carl Hasselbalch,1 Ole Weis Bjerrum,7 Christen Lykkegaard Andersen1,7 1Department of Hematology, Zealand University Hospital, University of Copenhagen, Roskilde, 2Research Centre for Prevention and Health, Rigshospitalet Glostrup, University of Copenhagen, Glostrup, 3Department of Hematology, Odense University Hospital, Odense, 4Department of Hematology, Vejle Hospital, Vejle, 5Department of Surgical Pathology, Zealand University Hospital, University of Copenhagen, Roskilde, 6Department of Surgical Pathology, Zealand University Hospital, University of Copenhagen, Næstved, 7Department of Hematology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark Aim: The Danish National Chronic Myeloid Neoplasia Registry (DCMR is a population-based clinical quality database, introduced to evaluate diagnosis and treatment of patients with chronic myeloid malignancies. The aim is to monitor the clinical quality at the national, regional, and hospital departmental levels and serve as a platform for research. Study population: The DCMR has nationwide coverage and contains information on patients diagnosed at hematology departments from January 2010 onward, including patients with essential thrombocythemia, polycythemia vera, myelofibrosis, unclassifiable myeloproliferative neoplasms, chronic myelomonocytic leukemia, and chronic myeloid leukemia. Main variables: Data are collected using standardized registration forms (so far up to four forms per patient, which are consecutively filled out online at time of diagnosis, after 2-year and 5-year follow-ups, and at end of follow-up. The forms include variables that describe clinical/paraclinical assessments, treatment, disease progression, and survival – disease-specific variables – as well as variables that are identical for all chronic myeloid malignancies. Descriptive

  15. Excision of Nucleopolyhedrovirus Form Transgenic Silkworm Using the CRISPR/Cas9 System

    Directory of Open Access Journals (Sweden)

    Zhanqi Dong

    2018-02-01

    Full Text Available The CRISPR/Cas9-mediated genome engineering has been shown to efficiently suppress infection by disrupting genes of the pathogen. We recently constructed transgenic lines expressing CRISPR/Cas9 and the double sgRNA target Bombyx mori nucleopolyhedrovirus (BmNPV immediate early-1 (ie-1 gene in the silkworm, respectively, and obtained four transgenic hybrid lines by G1 generation hybridization: Cas9(-/sgRNA(-, Cas9(+/sgRNA(-, Cas9(-/sgRNA(+, and Cas9(+/sgRNA(+. We demonstrated that the Cas9(+/sgRNA(+ transgenic lines effectively edited the target site of the BmNPV genome, and large fragment deletion was observed after BmNPV infection. Further antiviral analysis of the Cas9(+/sgRNA(+ transgenic lines shows that the median lethal dose (LD50 is 1,000-fold higher than the normal lines after inoculation with occlusion bodies. The analysis of economic characters and off-target efficiency of Cas9(+/sgRNA(+ transgenic hybrid line showed no significant difference compared with the normal lines. Our findings indicate that CRISPR/Cas9-mediated genome engineering more effectively targets the BmNPV genomes and could be utilized as an insect antiviral treatment.

  16. Excision of Nucleopolyhedrovirus Form Transgenic Silkworm Using the CRISPR/Cas9 System.

    Science.gov (United States)

    Dong, Zhanqi; Dong, Feifan; Yu, Xinbo; Huang, Liang; Jiang, Yaming; Hu, Zhigang; Chen, Peng; Lu, Cheng; Pan, Minhui

    2018-01-01

    The CRISPR/Cas9-mediated genome engineering has been shown to efficiently suppress infection by disrupting genes of the pathogen. We recently constructed transgenic lines expressing CRISPR/Cas9 and the double sgRNA target Bombyx mori nucleopolyhedrovirus (BmNPV) immediate early-1 ( ie-1 ) gene in the silkworm, respectively, and obtained four transgenic hybrid lines by G1 generation hybridization: Cas9(-)/sgRNA(-), Cas9(+)/sgRNA(-), Cas9(-)/sgRNA(+), and Cas9(+)/sgRNA(+). We demonstrated that the Cas9(+)/sgRNA(+) transgenic lines effectively edited the target site of the BmNPV genome, and large fragment deletion was observed after BmNPV infection. Further antiviral analysis of the Cas9(+)/sgRNA(+) transgenic lines shows that the median lethal dose (LD50) is 1,000-fold higher than the normal lines after inoculation with occlusion bodies. The analysis of economic characters and off-target efficiency of Cas9(+)/sgRNA(+) transgenic hybrid line showed no significant difference compared with the normal lines. Our findings indicate that CRISPR/Cas9-mediated genome engineering more effectively targets the BmNPV genomes and could be utilized as an insect antiviral treatment.

  17. Delivery strategies of the CRISPR-Cas9 gene-editing system for therapeutic applications.

    Science.gov (United States)

    Liu, Chang; Zhang, Li; Liu, Hao; Cheng, Kun

    2017-11-28

    The CRISPR-Cas9 genome-editing system is a part of the adaptive immune system in archaea and bacteria to defend against invasive nucleic acids from phages and plasmids. The single guide RNA (sgRNA) of the system recognizes its target sequence in the genome, and the Cas9 nuclease of the system acts as a pair of scissors to cleave the double strands of DNA. Since its discovery, CRISPR-Cas9 has become the most robust platform for genome engineering in eukaryotic cells. Recently, the CRISPR-Cas9 system has triggered enormous interest in therapeutic applications. CRISPR-Cas9 can be applied to correct disease-causing gene mutations or engineer T cells for cancer immunotherapy. The first clinical trial using the CRISPR-Cas9 technology was conducted in 2016. Despite the great promise of the CRISPR-Cas9 technology, several challenges remain to be tackled before its successful applications for human patients. The greatest challenge is the safe and efficient delivery of the CRISPR-Cas9 genome-editing system to target cells in human body. In this review, we will introduce the molecular mechanism and different strategies to edit genes using the CRISPR-Cas9 system. We will then highlight the current systems that have been developed to deliver CRISPR-Cas9 in vitro and in vivo for various therapeutic purposes. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Functional Insights Revealed by the Kinetic Mechanism of CRISPR/Cas9.

    Science.gov (United States)

    Raper, Austin T; Stephenson, Anthony A; Suo, Zucai

    2018-02-28

    The discovery of prokaryotic adaptive immunity prompted widespread use of the RNA-guided clustered regularly interspaced short palindromic repeat (CRISPR)-associated (Cas) endonuclease Cas9 for genetic engineering. However, its kinetic mechanism remains undefined, and details of DNA cleavage are poorly characterized. Here, we establish a kinetic mechanism of Streptococcus pyogenes Cas9 from guide-RNA binding through DNA cleavage and product release. Association of DNA to the binary complex of Cas9 and guide-RNA is rate-limiting during the first catalytic turnover, while DNA cleavage from a pre-formed ternary complex of Cas9, guide-RNA, and DNA is rapid. Moreover, an extremely slow release of DNA products essentially restricts Cas9 to be a single-turnover enzyme. By simultaneously measuring the contributions of the HNH and RuvC nuclease activities of Cas9 to DNA cleavage, we also uncovered the kinetic basis by which HNH conformationally regulates the RuvC cleavage activity. Together, our results provide crucial kinetic and functional details regarding Cas9 which will inform gene-editing experiments, guide future research to understand off-target DNA cleavage by Cas9, and aid in the continued development of Cas9 as a biotechnological tool.

  19. RNA-guided transcriptional regulation in planta via synthetic dCas9-based transcription factors

    KAUST Repository

    Piatek, Agnieszka Anna

    2014-11-14

    Targeted genomic regulation is a powerful approach to accelerate trait discovery and development in agricultural biotechnology. Bacteria and archaea use clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) regulatory systems for adaptive molecular immunity against foreign nucleic acids introduced by invading phages and conjugative plasmids. The type II CRISPR/Cas system has been adapted for genome editing in many cell types and organisms. A recent study used the catalytically inactive Cas9 (dCas9) protein combined with guide-RNAs (gRNAs) as a DNA-targeting platform to modulate gene expression in bacterial, yeast, and human cells. Here, we modified this DNA-targeting platform for targeted transcriptional regulation in planta by developing chimeric dCas9-based transcriptional activators and repressors. To generate transcriptional activators, we fused the dCas9 C-terminus with the activation domains of EDLL and TAL effectors. To generate a transcriptional repressor, we fused the dCas9 C-terminus with the SRDX repression domain. Our data demonstrate that dCas9 fusion with the EDLL activation domain (dCas9:EDLL) and the TAL activation domain (dCas9:TAD), guided by gRNAs complementary to selected promoter elements, induce strong transcriptional activation on Bs3

  20. Broadening the targeting range of Staphylococcus aureus CRISPR-Cas9 by modifying PAM recognition.

    Science.gov (United States)

    Kleinstiver, Benjamin P; Prew, Michelle S; Tsai, Shengdar Q; Nguyen, Nhu T; Topkar, Ved V; Zheng, Zongli; Joung, J Keith

    2015-12-01

    CRISPR-Cas9 nucleases target specific DNA sequences using a guide RNA but also require recognition of a protospacer adjacent motif (PAM) by the Cas9 protein. Although longer PAMs can potentially improve the specificity of genome editing, they limit the range of sequences that Cas9 orthologs can target. One potential strategy to relieve this restriction is to relax the PAM recognition specificity of Cas9. Here we used molecular evolution to modify the NNGRRT PAM of Staphylococcus aureus Cas9 (SaCas9). One variant we identified, referred to as KKH SaCas9, showed robust genome editing activities at endogenous human target sites with NNNRRT PAMs, thereby increasing SaCas9 targeting range by two- to fourfold. Using GUIDE-seq, we show that wild-type and KKH SaCas9 induce comparable numbers of off-target effects in human cells. Our strategy for evolving PAM specificity does not require structural information and therefore should be applicable to a wide range of Cas9 orthologs.

  1. RNA-guided transcriptional regulation in planta via synthetic dCas9-based transcription factors

    KAUST Repository

    Piatek, Agnieszka Anna; Ali, Zahir; Baazim, Hatoon; Li, Lixin; Abulfaraj, Aala A.; Alshareef, Sahar; Aouida, Mustapha; Mahfouz, Magdy M.

    2014-01-01

    Targeted genomic regulation is a powerful approach to accelerate trait discovery and development in agricultural biotechnology. Bacteria and archaea use clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) regulatory systems for adaptive molecular immunity against foreign nucleic acids introduced by invading phages and conjugative plasmids. The type II CRISPR/Cas system has been adapted for genome editing in many cell types and organisms. A recent study used the catalytically inactive Cas9 (dCas9) protein combined with guide-RNAs (gRNAs) as a DNA-targeting platform to modulate gene expression in bacterial, yeast, and human cells. Here, we modified this DNA-targeting platform for targeted transcriptional regulation in planta by developing chimeric dCas9-based transcriptional activators and repressors. To generate transcriptional activators, we fused the dCas9 C-terminus with the activation domains of EDLL and TAL effectors. To generate a transcriptional repressor, we fused the dCas9 C-terminus with the SRDX repression domain. Our data demonstrate that dCas9 fusion with the EDLL activation domain (dCas9:EDLL) and the TAL activation domain (dCas9:TAD), guided by gRNAs complementary to selected promoter elements, induce strong transcriptional activation on Bs3

  2. Cas9-nickase-mediated genome editing corrects hereditary tyrosinemia in rats.

    Science.gov (United States)

    Shao, Yanjiao; Wang, Liren; Guo, Nana; Wang, Shengfei; Yang, Lei; Li, Yajing; Wang, Mingsong; Yin, Shuming; Han, Honghui; Zeng, Li; Zhang, Ludi; Hui, Lijian; Ding, Qiurong; Zhang, Jiqin; Geng, Hongquan; Liu, Mingyao; Li, Dali

    2018-05-04

    Hereditary tyrosinemia type I (HTI) is a metabolic genetic disorder caused by mutation of fumarylacetoacetate hydrolase (FAH). Because of the accumulation of toxic metabolites, HTI causes severe liver cirrhosis, liver failure, and even hepatocellular carcinoma. HTI is an ideal model for gene therapy, and several strategies have been shown to ameliorate HTI symptoms in animal models. Although CRISPR/Cas9-mediated genome editing is able to correct the Fah mutation in mouse models, WT Cas9 induces numerous undesired mutations that have raised safety concerns for clinical applications. To develop a new method for gene correction with high fidelity, we generated a Fah mutant rat model to investigate whether Cas9 nickase (Cas9n)-mediated genome editing can efficiently correct the Fah First, we confirmed that Cas9n rarely induces indels in both on-target and off-target sites in cell lines. Using WT Cas9 as a positive control, we delivered Cas9n and the repair donor template/single guide (sg)RNA through adenoviral vectors into HTI rats. Analyses of the initial genome editing efficiency indicated that only WT Cas9 but not Cas9n causes indels at the on-target site in the liver tissue. After receiving either Cas9n or WT Cas9-mediated gene correction therapy, HTI rats gained weight steadily and survived. Fah-expressing hepatocytes occupied over 95% of the liver tissue 9 months after the treatment. Moreover, CRISPR/Cas9-mediated gene therapy prevented the progression of liver cirrhosis, a phenotype that could not be recapitulated in the HTI mouse model. These results strongly suggest that Cas9n-mediated genome editing is a valuable and safe gene therapy strategy for this genetic disease. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Evolution of resistance against CRISPR/Cas9 gene drive

    OpenAIRE

    Clark, Andrew; Unckless, Robert; Messer, Philipp

    2016-01-01

    CRISPR/Cas9 gene drive (CGD) promises to be a highly adaptable approach for spreading genetically engineered alleles throughout a species, even if those alleles impair reproductive success. CGD has been shown to be effective in laboratory crosses of insects, yet it remains unclear to what extent potential resistance mechanisms will affect the dynamics of this process in large natural populations. Here we develop a comprehensive population genetic framework for modeling CGD dynamics, which inc...

  4. Communications en cas de catastrophe faisant appel aux TIC pour ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Communications en cas de catastrophe faisant appel aux TIC pour les collectivités vulnérables des Caraïbes. De récents événements survenus dans les Caraïbes ont mis en relief les insuffisances des mesures régionales et nationales de préparation aux catastrophes. On manque particulièrement de systèmes d'alerte ...

  5. Application of the nanobiotechnology with the system CRISP-Cas

    OpenAIRE

    Liceth Xiomara Sáenz-Castiblanco; Maritza Angarita-Merchán; Diana Paola Lopez-Velandia

    2017-01-01

    Introduction: Nanobiotechnology and synthetic biology are sciences that impact today with the launching of innovative and beneficial applications for the human being. These sciences have been amalgamated to manufacture new components for the construction of totally artificial cells and the creation of synthetic biomolecules. Objective: To know the applications of nanobiotechnology related to the use of the system CRISPR/Cas in the storage of bacterial DNA and therapeutic alternatives. Materia...

  6. Cas d'une loi exponentielle Bayesian predict

    African Journals Online (AJOL)

    DK

    Avec des données groupées : Cas d'une loi exponentielle. Bayesian predictions of order statistics with grouped data: The case of an exponential law. Assia Chadli* & Asma Meradji. Laboratoire LaPS, Département de Mathématiques, Faculté des Sciences. Université Badji Mokhtar Annaba, BP 12, 23000, Annaba, Algérie.

  7. Building Cre Knockin Rat Lines Using CRISPR/Cas9.

    Science.gov (United States)

    Ma, Yuanwu; Zhang, Lianfeng; Huang, Xingxu

    2017-01-01

    Conditional gene inactivation strategy helps researchers to study the gene functions that are critical in embryogenesis or in defined tissues of adulthood. The Cre/loxP system is widely used for conditional gene inactivation/activation in cells or organisms. Cre knockin animal lines are essential for gene expression or inactivation in a spatially and temporally restricted manner. However, to generate a Cre knockin line by traditional approach is laborious. Recently, the clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR/Cas9) has been proven as a simple and efficient genome-editing tool. We have used CRISPR/Cas9 system to generate rat strains that carry Cre genes in different targeted gene loci by direct delivery of gRNAs/Cas9/donors into fertilized eggs. Here, we described a stepwise procedure for the generation of Cre knockin rat, including target site selection, RNA preparation, the construction of the template donor, pronuclear injection, and the genotyping of precise Cre insertion in F 0 rats. Taken together, the establishment of Cre knockin line can be achieved within 6 weeks.

  8. Sensitizing pathogens to antibiotics using the CRISPR-Cas system.

    Science.gov (United States)

    Goren, Moran; Yosef, Ido; Qimron, Udi

    2017-01-01

    The extensive use of antibiotics over the last century has resulted in a significant artificial selection pressure for antibiotic-resistant pathogens to evolve. Various strategies to fight these pathogens have been introduced including new antibiotics, naturally-derived enzymes/peptides that specifically target pathogens and bacteriophages that lyse these pathogens. A new tool has recently been introduced in the fight against drug-resistant pathogens-the prokaryotic defense mechanism-clustered regularly interspaced short palindromic repeats-CRISPR associated (CRISPR-Cas) system. The CRISPR-Cas system acts as a nuclease that can be guided to cleave any target DNA, allowing sophisticated, yet feasible, manipulations of pathogens. Here, we review pioneering studies that use the CRISPR-Cas system to specifically edit bacterial populations, eliminate their resistance genes and combine these two strategies in order to produce an artificial selection pressure for antibiotic-sensitive pathogens. We suggest that intelligent design of this system, along with efficient delivery tools into pathogens, may significantly reduce the threat of antibiotic-resistant pathogens. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. CRISPR/Cas-mediated targeted mutagenesis in Daphnia magna.

    Directory of Open Access Journals (Sweden)

    Takashi Nakanishi

    Full Text Available The water flea Daphnia magna has been used as an animal model in ecology, evolution, and environmental sciences. Thanks to the recent progress in Daphnia genomics, genetic information such as the draft genome sequence and expressed sequence tags (ESTs is now available. To investigate the relationship between phenotypes and the available genetic information about Daphnia, some gene manipulation methods have been developed. However, a technique to induce targeted mutagenesis into Daphnia genome remains elusive. To overcome this problem, we focused on an emerging genome editing technique mediated by the clustered regularly interspaced short palindromic repeats/CRISPR-associated (CRISPR/Cas system to introduce genomic mutations. In this study, we targeted a functionally conserved regulator of eye development, the eyeless gene in D. magna. When we injected Cas9 mRNAs and eyeless-targeting guide RNAs into eggs, 18-47% of the survived juveniles exhibited abnormal eye morphology. After maturation, up to 8.2% of the adults produced progenies with deformed eyes, which carried mutations in the eyeless loci. These results showed that CRISPR/Cas system could introduce heritable mutations into the endogenous eyeless gene in D. magna. This is the first report of a targeted gene knockout technique in Daphnia and will be useful in uncovering Daphnia gene functions.

  10. Marrow donor registry and cord blood bank in Taiwan.

    Science.gov (United States)

    Lee, Tsung Dao

    2002-08-01

    Unrelated Bone marrow transplant was initiated thirty years ago. Though there are over millions of donors registered with the bone marrow registries worldwide, Asian patients rarely find a match with all these donors. Tzu Chi Marrow Donor Registry was established to meet this need. It has become the largest Asian marrow donor registry in the world. With the introduction of high technology to test the HLA of the donors and recipients, the success rate of bone marrow transplant is greatly improved among Asian countries. 50% of blood disease Asian patients who cannot find a bone marrow matched donor will be complemented by the establishment of cord blood banks in Taiwan.

  11. Italian registry of cardiac magnetic resonance

    Energy Technology Data Exchange (ETDEWEB)

    Francone, Marco [Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome (Italy); Di Cesare, Ernesto, E-mail: ernesto.dicesare@cc.univaq.it [Dipartimento di Scienze Cliniche Applicate e Biotecnologie, Università di L’Aquila (Italy); Cademartiri, Filippo [Cardio-Vascular Imaging Unit, Giovanni XXIII Hospital, Monastier di Treviso, TV (Italy); Erasmus Medical Center University, Rotterdam (Netherlands); Pontone, Gianluca [IRCCS Centro Cardiologico Monzino (Italy); Lovato, Luigi [Policlinico S. Orsola Bologna (Italy); Matta, Gildo [Azienda ospedaliera G Brotzu Cagliari (Italy); Secchi, Francesco [IRCCS Policlinico San Donato, Radiology Unit, Milan (Italy); Maffei, Erica [Cardio-Vascular Imaging Unit, Giovanni XXIII Hospital, Monastier di Treviso, TV (Italy); Erasmus Medical Center University, Rotterdam (Netherlands); Pradella, Silvia [Azienda Ospedaliera Universitaria Careggi (Italy); Carbone, Iacopo [Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome (Italy); Marano, Riccardo [Policlinico Gemelli, Università Cattolica Roma (Italy); Bacigalupo, Lorenzo [Ospedale Galliera, Genova (Italy); Chiodi, Elisabetta [Ospedale S. Anna Ferrara (Italy); Donato, Rocco [Azienda Ospedaliera Universitaria G. Martino, Me (Italy); Sbarbati, Stefano [Ospedale Madre Giuseppina Vannini, Roma (Italy); De Cobelli, Francesco [IRCCS S. Raffaele, Università Vita Salute, Milano (Italy); Di Renzi, Paolo [Fate Bene Fratelli Isola tiberina, Roma (Italy); Ligabue, Guido; Mancini, Andrea [Azienda Ospedaliera-Universitaria Policlinico di Modena (Italy); Palmieri, Francesco [Diparimento di Diagnostica per immagini e radiologia interventistica, Ospedale S. Maria delle Grazie, Pozzuoli, Napoli (Italy); and others

    2014-01-15

    Objectives: Forty sites were involved in this multicenter and multivendor registry, which sought to evaluate indications, spectrum of protocols, impact on clinical decision making and safety profile of cardiac magnetic resonance (CMR). Materials and methods: Data were prospectively collected on a 6-month period and included 3376 patients (47.2 ± 19 years; range 1–92 years). Recruited centers were asked to complete a preliminary general report followed by a single form/patient. Referral physicians were not required to exhibit any specific certificate of competency in CMR imaging. Results: Exams were performed with 1.5 T scanners in 96% of cases followed by 3 T (3%) and 1 T (1%) magnets and contrast was administered in 84% of cases. The majority of cases were performed for the workup of inflammatory heart disease/cardiomyopathies representing overall 55.7% of exams followed by the assessment of myocardial viability and acute infarction (respectively 6.9% and 5.9% of patients). In 49% of cases the final diagnosis provided was considered relevant and with impact on patient's clinical/therapeutic management. Safety evaluation revealed 30 (0.88%) clinical events, most of which due to patient's preexisting conditions. Radiological reporting was recorded in 73% of exams. Conclusions: CMR is performed in a large number of centers in Italy with relevant impact on clinical decision making and high safety profile.

  12. Le syndrome néphrotique idiopathique (SNI) de l’enfant à Dakar: à propos de 40 cas

    Science.gov (United States)

    Keita, Younoussa; Lemrabott, Ahmed Tall; Sylla, Assane; Niang, Babacar; Ka, El Hadji Fary; Dial, Chérif Mohamed; Ndongo, Aliou Abdoulaye; Sow, Amadou; Moreira, Claude; Niang, Abdou; Ndiaye, Ousmane; Diouf, Boucar; Sall, Mouhamadou Guélaye

    2017-01-01

    Introduction L’objectif de ce travail était d’analyser les caractéristiques diagnostiques, thérapeutiques et évolutives de l’enfant atteint de néphrose dans un service de pédiatrie de Dakar. Méthodes L’étude était réalisée au service de pédiatrie de l’hôpital Aristide Le Dantec. Il s’agissait d’une étude rétrospective sur une période de 03 ans allant du 1er janvier 2012 au 31 décembre 2014. Ont été inclus tous les patients âgés de 02 ans à 12 ans présentant un tableau de Syndrome néphrotique idiopathique. Résultats Quarante cas de néphrose étaient colligés soit une prévalence de 23% parmi les néphropathies prises en charge dans le service. L’âge moyen était de 7,11± 3,14 ans. Le syndrome néphrotique était pur chez 72,5% (n=29) des patients. Les œdèmes des membres inférieurs étaient présents chez 100% des patients, l’oligurie dans 55% (n=22) et l’HTA dans 5% (n=2) des cas. La protéinurie moyenne était de 145,05 ± 85,54 mg/kg/24heures. La protidémie moyenne était de 46,42 ±7,88 g/L et l’albuminémie moyenne de 17,90 ± 7,15 g/L. Trente-neuf patients avaient reçu une corticothérapie à base de prednisone. La corticosensibilité était retenue chez 77% (n=30) des patients et la corticorésistance chez 13% (n=5) des cas. Le facteur de mauvaise réponse à la corticothérapie était un niveau de protéinurie initiale supérieure à 150 mg/kg/jour (p = 0,024). La biopsie rénale était réalisée chez 18% (n=7) des patients et retrouvait dans 57,2% (n=4) des cas une hyalinose segmentaire et focale. Le cyclophosphamide et l’azathioprine étaient associés aux corticoïdes dans 10% (n=4) des cas chacun. Le taux de rémission globale était de 89,8%. L’évolution vers l’insuffisance rénale chronique était notée chez trois (03) des patients. Conclusion La néphrose représentait près du quart des néphropathies prises en charge dans notre service. Le taux de rémission globale était élevé. Le

  13. The Pediatric Emergency Care Applied Research Network Registry: A Multicenter Electronic Health Record Registry of Pediatric Emergency Care.

    Science.gov (United States)

    Deakyne Davies, Sara J; Grundmeier, Robert W; Campos, Diego A; Hayes, Katie L; Bell, Jamie; Alessandrini, Evaline A; Bajaj, Lalit; Chamberlain, James M; Gorelick, Marc H; Enriquez, Rene; Casper, T Charles; Scheid, Beth; Kittick, Marlena; Dean, J Michael; Alpern, Elizabeth R

    2018-04-01

     Electronic health record (EHR)-based registries allow for robust data to be derived directly from the patient clinical record and can provide important information about processes of care delivery and patient health outcomes.  A data dictionary, and subsequent data model, were developed describing EHR data sources to include all processes of care within the emergency department (ED). ED visit data were deidentified and XML files were created and submitted to a central data coordinating center for inclusion in the registry. Automated data quality control occurred prior to submission through an application created for this project. Data quality reports were created for manual data quality review.  The Pediatric Emergency Care Applied Research Network (PECARN) Registry, representing four hospital systems and seven EDs, demonstrates that ED data from disparate health systems and EHR vendors can be harmonized for use in a single registry with a common data model. The current PECARN Registry represents data from 2,019,461 pediatric ED visits, 894,503 distinct patients, more than 12.5 million narrative reports, and 12,469,754 laboratory tests and continues to accrue data monthly.  The Registry is a robust harmonized clinical registry that includes data from diverse patients, sites, and EHR vendors derived via data extraction, deidentification, and secure submission to a central data coordinating center. The data provided may be used for benchmarking, clinical quality improvement, and comparative effectiveness research. Schattauer.

  14. CRISPR-Cas Systems in Bacteroides fragilis, an Important Pathobiont in the Human Gut Microbiome

    Science.gov (United States)

    Tajkarimi, Mehrdad; Wexler, Hannah M.

    2017-01-01

    Background: While CRISPR-Cas systems have been identified in bacteria from a wide variety of ecological niches, there are no studies to describe CRISPR-Cas elements in Bacteroides species, the most prevalent anaerobic bacteria in the lower intestinal tract. Microbes of the genus Bacteroides make up ~25% of the total gut microbiome. Bacteroides fragilis comprises only 2% of the total Bacteroides in the gut, yet causes of >70% of Bacteroides infections. The factors causing it to transition from benign resident of the gut microbiome to virulent pathogen are not well understood, but a combination of horizontal gene transfer (HGT) of virulence genes and differential transcription of endogenous genes are clearly involved. The CRISPR-Cas system is a multi-functional system described in prokaryotes that may be involved in control both of HGT and of gene regulation. Results: Clustered regularly interspaced short palindromic repeats (CRISPR) elements in all strains of B. fragilis (n = 109) with publically available genomes were identified. Three different CRISPR-Cas types, corresponding most closely to Type IB, Type IIIB, and Type IIC, were identified. Thirty-five strains had two CRISPR-Cas types, and three strains included all three CRISPR-Cas types in their respective genomes. The cas1 gene in the Type IIIB system encoded a reverse-transcriptase/Cas1 fusion protein rarely found in prokaryotes. We identified a short CRISPR (3 DR) with no associated cas genes present in most of the isolates; these CRISPRs were found immediately upstream of a hipA/hipB operon and we speculate that this element may be involved in regulation of this operon related to formation of persister cells during antimicrobial exposure. Also, blood isolates of B. fragilis did not have Type IIC CRISPR-Cas systems and had atypical Type IIIB CRISPR-Cas systems that were lacking adjacent cas genes. Conclusions: This is the first systematic report of CRISPR-Cas systems in a wide range of B. fragilis strains

  15. CRISPR-Cas Systems in Bacteroides fragilis, an Important Pathobiont in the Human Gut Microbiome

    Directory of Open Access Journals (Sweden)

    Mehrdad Tajkarimi

    2017-11-01

    Full Text Available Background: While CRISPR-Cas systems have been identified in bacteria from a wide variety of ecological niches, there are no studies to describe CRISPR-Cas elements in Bacteroides species, the most prevalent anaerobic bacteria in the lower intestinal tract. Microbes of the genus Bacteroides make up ~25% of the total gut microbiome. Bacteroides fragilis comprises only 2% of the total Bacteroides in the gut, yet causes of >70% of Bacteroides infections. The factors causing it to transition from benign resident of the gut microbiome to virulent pathogen are not well understood, but a combination of horizontal gene transfer (HGT of virulence genes and differential transcription of endogenous genes are clearly involved. The CRISPR-Cas system is a multi-functional system described in prokaryotes that may be involved in control both of HGT and of gene regulation.Results: Clustered regularly interspaced short palindromic repeats (CRISPR elements in all strains of B. fragilis (n = 109 with publically available genomes were identified. Three different CRISPR-Cas types, corresponding most closely to Type IB, Type IIIB, and Type IIC, were identified. Thirty-five strains had two CRISPR-Cas types, and three strains included all three CRISPR-Cas types in their respective genomes. The cas1 gene in the Type IIIB system encoded a reverse-transcriptase/Cas1 fusion protein rarely found in prokaryotes. We identified a short CRISPR (3 DR with no associated cas genes present in most of the isolates; these CRISPRs were found immediately upstream of a hipA/hipB operon and we speculate that this element may be involved in regulation of this operon related to formation of persister cells during antimicrobial exposure. Also, blood isolates of B. fragilis did not have Type IIC CRISPR-Cas systems and had atypical Type IIIB CRISPR-Cas systems that were lacking adjacent cas genes.Conclusions: This is the first systematic report of CRISPR-Cas systems in a wide range of B

  16. The Mataró Stroke Registry: a 10-year registry in a community hospital.

    Science.gov (United States)

    Palomeras Soler, E; Fossas Felip, P; Casado Ruiz, V; Cano Orgaz, A; Sanz Cartagena, P; Muriana Batiste, D

    2015-06-01

    A prospective stroke registry leads to improved knowledge of the disease. We present data on the Mataró Hospital Registry. In February-2002 a prospective stroke registry was initiated in our hospital. It includes sociodemographic data, previous diseases, clinical, topographic, etiological and prognostic data. We have analyzed the results of the first 10 years. A total of 2,165 patients have been included, 54.1% male, mean age 73 years. The most frequent vascular risk factor was hypertension (65.4%). Median NIHSS on admission: 3 (interquartile range, 1-8). Stroke subtype: 79.7% ischemic strokes, 10.9% hemorrhagic, and 9.4% TIA. Among ischemic strokes, the etiology was cardioembolic in 26.5%, large-vessel disease in 23.7%, and small-vessel in 22.9%. The most frequent topography of hemorrhages was lobar (47.4%), and 54.8% were attributed to hypertension. The median hospital stay was 8 days. At discharge, 60.7% of patients were able to return directly to their own home, and 52.7% were independent for their daily life activities. After 3 months these percentages were 76.9% and 62.9%, respectively. Hospital mortality was 6.5%, and after 3 months 10.9%. Our patient's profile is similar to those of other series, although the severity of strokes was slightly lower. Length of hospital stay, short-term and medium term disability, and mortality rates are good, if we compare them with other series. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  17. The Prostate Cancer Registry: monitoring patterns and quality of care for men diagnosed with prostate cancer.

    Science.gov (United States)

    Evans, Sue M; Millar, Jeremy L; Wood, Julie M; Davis, Ian D; Bolton, Damien; Giles, Graham G; Frydenberg, Mark; Frauman, Albert; Costello, Antony; McNeil, John J

    2013-04-01

    To establish a pilot population-based clinical registry with the aim of monitoring the quality of care provided to men diagnosed with prostate cancer. All men aged >18 years from the contributing hospitals in Victoria, Australia, who have a diagnosis of prostate cancer confirmed by histopathology report notified to the Victorian Cancer Registry are eligible for inclusion in the Prostate Cancer Registry (PCR). A literature review was undertaken aiming to identify existing quality indicators and source evidence-based guidelines from both Australia and internationally. A Steering Committee was established to determine the minimum dataset, select quality indicators to be reported back to clinicians, identify the most effective recruitment strategy, and provide a governance structure for data requests; collection, analysis and reporting of data; and managing outliers. A minimum dataset comprising 72 data items is collected by the PCR, enabling ten quality indicators to be collected and reported. Outcome measures are risk adjusted according to the established National Comprehensive Cancer Network and Cancer of the Prostate Risk Assessment Score (surgery only) risk stratification model. Recruitment to the PCR occurs concurrently with mandatory notification to the state-based Cancer Registry. The PCR adopts an opt-out consent process to maximize recruitment. The data collection approach is standardized, using a hybrid of data linkage and manual collection, and data collection forms are electronically scanned into the PCR. A data access policy and escalation policy for mortality outliers has been developed. The PCR provides potential for high-quality population-based data to be collected and managed within a clinician-led governance framework. This approach satisfies the requirement for health services to establish quality assessment, at the same time as providing clinically credible data to clinicians to drive practice improvement. © 2012 THE AUTHORS. BJU INTERNATIONAL

  18. Antiviral Goes Viral: Harnessing CRISPR/Cas9 to Combat Viruses in Humans.

    Science.gov (United States)

    Soppe, Jasper Adriaan; Lebbink, Robert Jan

    2017-10-01

    The clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) systems are RNA-guided sequence-specific prokaryotic antiviral immune systems. In prokaryotes, small RNA molecules guide Cas effector endonucleases to invading foreign genetic elements in a sequence-dependent manner, resulting in DNA cleavage by the endonuclease upon target binding. A rewired CRISPR/Cas9 system can be used for targeted and precise genome editing in eukaryotic cells. CRISPR/Cas has also been harnessed to target human pathogenic viruses as a potential new antiviral strategy. Here, we review recent CRISPR/Cas9-based approaches to combat specific human viruses in humans and discuss challenges that need to be overcome before CRISPR/Cas9 may be used in the clinic as an antiviral strategy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Establishment of the Fox Chase Network Breast Cancer Risk Registry

    National Research Council Canada - National Science Library

    Daly, Mary

    1997-01-01

    .... The development of the Fox Chase Cancer Center Breast Cancer Risk Registry was proposed to facilitate research in the epidemiologic and genetic predictors of disease and will permit evaluation...

  20. Recent progress of the United States transuranium and uranium registries

    International Nuclear Information System (INIS)

    Kathren, R.L.

    1986-01-01

    This paper provides a brief overview of the history and objectives of the US Transuranium and Uranium Registries along with a discussion of some recent activities and accomplishments of these two parallel programs. 17 refs

  1. Functional requirements regarding medical registries--preliminary results.

    Science.gov (United States)

    Oberbichler, Stefan; Hörbst, Alexander

    2013-01-01

    The term medical registry is used to reference tools and processes to support clinical or epidemiologic research or provide a data basis for decisions regarding health care policies. In spite of this wide range of applications the term registry and the functional requirements which a registry should support are not clearly defined. This work presents preliminary results of a literature review to discover functional requirements which form a registry. To extract these requirements a set of peer reviewed articles was collected. These set of articles was screened by using methods from qualitative research. Up to now most discovered functional requirements focus on data quality (e. g. prevent transcription error by conducting automatic domain checks).

  2. Clinical features of paediatric pulmonary hypertension : a registry study

    NARCIS (Netherlands)

    Berger, Rolf M. F.; Beghetti, Maurice; Humpl, Tilman; Raskob, Gary E.; Ivy, D. Dunbar; Jing, Zhi-Cheng; Bonnet, Damien; Schulze-Neick, Ingram; Barst, Robyn J.

    2012-01-01

    Background Paediatric pulmonary hypertension, is an important cause of morbidity and mortality, and is insufficiently characterised in children. The Tracking Outcomes and Practice in Pediatric Pulmonary Hypertension (TOPP) registry is a global, prospective study designed to provide information about

  3. RNA-guided Transcriptional Regulation in Plants via dCas9 Chimeric Proteins

    KAUST Repository

    Baazim, Hatoon

    2014-05-01

    Developing targeted genome regulation approaches holds much promise for accelerating trait discovery and development in agricultural biotechnology. Clustered Regularly Interspaced Palindromic Repeats (CRISPRs)/CRISPR associated (Cas) system provides bacteria and archaea with an adaptive molecular immunity mechanism against invading nucleic acids through phages and conjugative plasmids. The type II CRISPR/Cas system has been adapted for genome editing purposes across a variety of cell types and organisms. Recently, the catalytically inactive Cas9 (dCas9) protein combined with guide RNAs (gRNAs) were used as a DNA-targeting platform to modulate the expression patterns in bacterial, yeast and human cells. Here, we employed this DNA-targeting system for targeted transcriptional regulation in planta by developing chimeric dCas9-based activators and repressors. For example, we fused to the C-terminus of dCas9 with the activation domains of EDLL and TAL effectors, respectively, to generate transcriptional activators, and the SRDX repression domain to generate transcriptional repressor. Our data demonstrate that the dCas9:EDLL and dCas9:TAD activators, guided by gRNAs complementary to promoter elements, induce strong transcriptional activation on episomal targets in plant cells. Moreover, our data suggest that the dCas9:SRDX repressor and the dCas9:EDLL and dCas9:TAD activators are capable of markedly repressing or activating, respectively, the transcription of an endogenous genomic target. Our data indicate that the CRISPR/dCas9:TFs DNA targeting system can be used in plants as a functional genomic tool and for biotechnological applications.

  4. System-level perturbations of cell metabolism using CRISPR/Cas9

    DEFF Research Database (Denmark)

    Jakociunas, Tadas; Jensen, Michael Krogh; Keasling, Jay

    2017-01-01

    CRISPR/Cas9 (clustered regularly interspaced palindromic repeats and the associated protein Cas9) techniques have made genome engineering and transcriptional reprogramming studies more advanced and cost-effective. For metabolic engineering purposes, the CRISPR-based tools have been applied...... previously possible. In this mini-review we highlight recent studies adopting CRISPR/Cas9 for systems-level perturbations and model-guided metabolic engineering....

  5. Modelling of slag emulsification and slag reduction in CAS-OB process

    OpenAIRE

    Sulasalmi, P. (Petri)

    2016-01-01

    Abstract Composition Adjustment by Sealed argon bubbling – Oxygen Blowing (CAS-OB) process is a ladle treatment process that was developed for chemical heating and alloying of steel. The main stages of the process are heating, (possible) alloying and reduction of slag. The CAS-OB process aims for homogenization and control of the composition and temperature of steel. In this dissertation, a mathematical reaction model was developed for the slag reduction stage of the CAS-OB process. Sl...

  6. The Danish Neuro-Oncology Registry

    Directory of Open Access Journals (Sweden)

    Hansen S

    2016-10-01

    Full Text Available Steinbjørn Hansen Department of Oncology, Odense University Hospital and Institute of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark Aim of database: The Danish Neuro-Oncology Registry (DNOR was established by the Danish Neuro-Oncology Group as a national clinical database. It was established for the purpose of supporting research and development in adult patients with primary brain tumors in Denmark. Study population: DNOR has registered clinical data on diagnostics and treatment of all adult patients diagnosed with glioma since January 1, 2009, which numbers approximately 400 patients each year. Main variables: The database contains information about symptoms, presurgical magnetic resonance imaging (MRI characteristics, performance status, surgical procedures, residual tumor on postsurgical MRI, postsurgical complications, diagnostic and histology codes, radiotherapy, and chemotherapy. Descriptive data: DNOR publishes annual reports on descriptive data. During the period of registration, postoperative MRI is performed in a higher proportion of the patients (Indicator II, and a higher proportion of patients have no residual tumor after surgical resection of the primary tumor (Indicator IV. Further data are available in the annual reports. The indicators reflect only minor elements of handling brain tumor patients. Another advantage of reporting indicators is the related multidisciplinary discussions giving a better understanding of what actually is going on, thereby facilitating the work on adjusting the national guidelines in the Danish Neuro-Oncology Group. Conclusion: The establishment of DNOR has optimized the quality in handling primary brain tumor patients in Denmark by reporting indicators and facilitating a better multidisciplinary collaboration at a national level. DNOR provides a valuable resource for research. Keywords: brain neoplasms, brain cancer, glioma, clinical quality indicators

  7. Les leishmanioses cutanées à Leishmania major et à Leishmania tropica au Maroc: aspects épidémio-cliniques comparatifs de 268 cas

    Science.gov (United States)

    Chiheb, Soumia; Slaoui, Widad; Mouttaqui, Tarik; Riyad, Meriem; Benchikhi, Hakima

    2014-01-01

    Introduction Depuis 1995, le Maroc a connu une réactivation des foyers de leishmanioses cutanées (LC) à L. major et une nouvelle répartition géographique des foyers à L. tropica. Le but de cette étude est de comparer les aspects épidémio-cliniques associés aux LC potentiellement dûes à L. major et à L. tropica. Méthodes Une étude rétrospective a colligé 268 cas de LC au service de dermatologie du CHU Ibn Rochd de Casablanca entre Janvier 1995 et Septembre 2010. Les données étaient analysées par Epi info version 3.5.1. Le test X2 était appliqué (Différence significative = p< 0,05). Résultats Deux cent soixante-huit cas de LC ont été colligés, dont 160 femmes et 108 hommes. Ils ont été répartis en 123 patients originaires des foyers à L.major et 145 patients originaires des foyers à L. tropica. L'aspect ulcéronodulaire, ulcérovégétant ou végétant était retrouvé dans 58 cas (47,2%) des cas de LC à L. major versus 24 cas (16,7%) dans la L.C à L. tropica. L'aspect papulonodulaire était retrouvé dans 84 cas (58%) de LC à L. tropica contre 41 cas (33,3%) de LC à L. major. Conclusion Dans la LC à L. major, l'atteinte des membres et les aspects cliniques végétant ou ulcéro-végétant restent toujours prédominants. Dans la L.C à L. tropica, l'atteinte papulonodulaire unique du visage reste prédominante mais des formes ulcéronodulaires, végétantes ou ulcérovégétantes existent également dans les foyers récents à L. tropica, prêtant à confusion cliniquement avec des LC à L. major. PMID:25810796

  8. Patient registries: useful tools for clinical research in myasthenia gravis.

    Science.gov (United States)

    Baggi, Fulvio; Mantegazza, Renato; Antozzi, Carlo; Sanders, Donald

    2012-12-01

    Clinical registries may facilitate research on myasthenia gravis (MG) in several ways: as a source of demographic, clinical, biological, and immunological data on large numbers of patients with this rare disease; as a source of referrals for clinical trials; and by allowing rapid identification of MG patients with specific features. Physician-derived registries have the added advantage of incorporating diagnostic and treatment data that may allow comparison of outcomes from different therapeutic approaches, which can be supplemented with patient self-reported data. We report the demographic analysis of MG patients in two large physician-derived registries, the Duke MG Patient Registry, at the Duke University Medical Center, and the INNCB MG Registry, at the Istituto Neurologico Carlo Besta, as a preliminary study to assess the consistency of the two data sets. These registries share a common structure, with an inner core of common data elements (CDE) that facilitate data analysis. The CDEs are concordant with the MG-specific CDEs developed under the National Institute of Neurological Disorders and Stroke Common Data Elements Project. © 2012 New York Academy of Sciences.

  9. Utility of an Australasian registry for children undergoing radiation treatment

    International Nuclear Information System (INIS)

    Ahern, Verity

    2014-01-01

    The aim of this study was to evaluate the utility of an Australasian registry ('the Registry') for children undergoing radiation treatment (RT). Children under the age of 16years who received a course of radiation between January 1997 and December 2010 and were enrolled on the Registry form the subjects of this study. A total of 2232 courses of RT were delivered, predominantly with radical intent (87%). Registrations fluctuated over time, but around one-half of children diagnosed with cancer undergo a course of RT. The most prevalent age range at time of RT was 10–15years, and the most common diagnoses were central nervous system tumours (34%) and acute lymphoblastic leukaemia (20%). The Registry provides a reflection of the patterns of care of children undergoing RT in Australia and a mechanism for determining the resources necessary to manage children by RT (human, facilities and emerging technologies, such as proton therapy). It lacks the detail to provide information on radiotherapy quality and disease outcomes which should be the subject of separate audit studies. The utility of the Registry has been hampered by its voluntary nature and varying needs for consent. Completion of registry forms is a logical requirement for inclusion in the definition of a subspecialist in paediatric radiation oncology.

  10. Presenting an Evaluation Model for the Cancer Registry Software.

    Science.gov (United States)

    Moghaddasi, Hamid; Asadi, Farkhondeh; Rabiei, Reza; Rahimi, Farough; Shahbodaghi, Reihaneh

    2017-12-01

    As cancer is increasingly growing, cancer registry is of great importance as the main core of cancer control programs, and many different software has been designed for this purpose. Therefore, establishing a comprehensive evaluation model is essential to evaluate and compare a wide range of such software. In this study, the criteria of the cancer registry software have been determined by studying the documents and two functional software of this field. The evaluation tool was a checklist and in order to validate the model, this checklist was presented to experts in the form of a questionnaire. To analyze the results of validation, an agreed coefficient of %75 was determined in order to apply changes. Finally, when the model was approved, the final version of the evaluation model for the cancer registry software was presented. The evaluation model of this study contains tool and method of evaluation. The evaluation tool is a checklist including the general and specific criteria of the cancer registry software along with their sub-criteria. The evaluation method of this study was chosen as a criteria-based evaluation method based on the findings. The model of this study encompasses various dimensions of cancer registry software and a proper method for evaluating it. The strong point of this evaluation model is the separation between general criteria and the specific ones, while trying to fulfill the comprehensiveness of the criteria. Since this model has been validated, it can be used as a standard to evaluate the cancer registry software.

  11. Non-viral delivery systems for CRISPR/Cas9-based genome editing: Challenges and opportunities.

    Science.gov (United States)

    Li, Ling; Hu, Shuo; Chen, Xiaoyuan

    2018-07-01

    In recent years, CRISPR (clustered regularly interspaced short palindromic repeat)/Cas (CRISPR-associated) genome editing systems have become one of the most robust platforms in basic biomedical research and therapeutic applications. To date, efficient in vivo delivery of the CRISPR/Cas9 system to the targeted cells remains a challenge. Although viral vectors have been widely used in the delivery of the CRISPR/Cas9 system in vitro and in vivo, their fundamental shortcomings, such as the risk of carcinogenesis, limited insertion size, immune responses and difficulty in large-scale production, severely limit their further applications. Alternative non-viral delivery systems for CRISPR/Cas9 are urgently needed. With the rapid development of non-viral vectors, lipid- or polymer-based nanocarriers have shown great potential for CRISPR/Cas9 delivery. In this review, we analyze the pros and cons of delivering CRISPR/Cas9 systems in the form of plasmid, mRNA, or protein and then discuss the limitations and challenges of CRISPR/Cas9-based genome editing. Furthermore, current non-viral vectors that have been applied for CRISPR/Cas9 delivery in vitro and in vivo are outlined in details. Finally, critical obstacles for non-viral delivery of CRISPR/Cas9 system are highlighted and promising strategies to overcome these barriers are proposed. Published by Elsevier Ltd.

  12. Single-stranded DNA cleavage by divergent CRISPR-Cas9 enzymes

    Science.gov (United States)

    Ma, Enbo; Harrington, Lucas B.; O’Connell, Mitchell R.; Zhou, Kaihong; Doudna, Jennifer A.

    2015-01-01

    Summary Double-stranded DNA (dsDNA) cleavage by Cas9 is a hallmark of type II CRISPR-Cas immune systems. Cas9–guide RNA complexes recognize 20-base-pair sequences in DNA and generate a site-specific double-strand break, a robust activity harnessed for genome editing. DNA recognition by all studied Cas9 enzymes requires a protospacer adjacent motif (PAM) next to the target site. We show that Cas9 enzymes from evolutionarily divergent bacteria can recognize and cleave single-stranded DNA (ssDNA) by an RNA-guided, PAM-independent recognition mechanism. Comparative analysis shows that in contrast to the type II-A S. pyogenes Cas9 that is widely used for genome engineering, the smaller type II-C Cas9 proteins have limited dsDNA binding and unwinding activity and promiscuous guide-RNA specificity. These results indicate that inefficiency of type II-C Cas9 enzymes for genome editing results from a limited ability to cleave dsDNA, and suggest that ssDNA cleavage was an ancestral function of the Cas9 enzyme family. PMID:26545076

  13. CRISPR/Cas9-Advancing Orthopoxvirus Genome Editing for Vaccine and Vector Development.

    Science.gov (United States)

    Okoli, Arinze; Okeke, Malachy I; Tryland, Morten; Moens, Ugo

    2018-01-22

    The clustered regularly interspaced short palindromic repeat (CRISPR)/associated protein 9 (Cas9) technology is revolutionizing genome editing approaches. Its high efficiency, specificity, versatility, flexibility, simplicity and low cost have made the CRISPR/Cas9 system preferable to other guided site-specific nuclease-based systems such as TALENs (Transcription Activator-like Effector Nucleases) and ZFNs (Zinc Finger Nucleases) in genome editing of viruses. CRISPR/Cas9 is presently being applied in constructing viral mutants, preventing virus infections, eradicating proviral DNA, and inhibiting viral replication in infected cells. The successful adaptation of CRISPR/Cas9 to editing the genome of Vaccinia virus paves the way for its application in editing other vaccine/vector-relevant orthopoxvirus (OPXV) strains. Thus, CRISPR/Cas9 can be used to resolve some of the major hindrances to the development of OPXV-based recombinant vaccines and vectors, including sub-optimal immunogenicity; transgene and genome instability; reversion of attenuation; potential of spread of transgenes to wildtype strains and close contacts, which are important biosafety and risk assessment considerations. In this article, we review the published literature on the application of CRISPR/Cas9 in virus genome editing and discuss the potentials of CRISPR/Cas9 in advancing OPXV-based recombinant vaccines and vectors. We also discuss the application of CRISPR/Cas9 in combating viruses of clinical relevance, the limitations of CRISPR/Cas9 and the current strategies to overcome them.

  14. CRISPR/Cas9 Inhibits Multiple Steps of HIV-1 Infection.

    Science.gov (United States)

    Yin, Lijuan; Hu, Siqi; Mei, Shan; Sun, Hong; Xu, Fengwen; Li, Jian; Zhu, Weijun; Liu, Xiaoman; Zhao, Fei; Zhang, Di; Cen, Shan; Liang, Chen; Guo, Fei

    2018-05-09

    CRISPR/Cas9 is an adaptive immune system where bacteria and archaea have evolved to resist the invading viruses and plasmid DNA by creating site-specific double-strand breaks in DNA. This study tested this gene editing system in inhibiting human immunodeficiency virus type 1 (HIV-1) infection by targeting the viral long terminal repeat and the gene coding sequences. Strong inhibition of HIV-1 infection by Cas9/gRNA was observed, which resulted not only from insertions and deletions (indels) that were introduced into viral DNA due to Cas9 cleavage, but also from the marked decrease in the levels of the late viral DNA products and the integrated viral DNA. This latter defect might have reflected the degradation of viral DNA that has not been immediately repaired after Cas9 cleavage. It was further observed that Cas9, when solely located in the cytoplasm, inhibits HIV-1 as strongly as the nuclear Cas9, except that the cytoplasmic Cas9 does not act on the integrated HIV-1 DNA and thus cannot be used to excise the latent provirus. Together, the results suggest that Cas9/gRNA is able to target and edit HIV-1 DNA both in the cytoplasm and in the nucleus. The inhibitory effect of Cas9 on HIV-1 is attributed to both the indels in viral DNA and the reduction in the levels of viral DNA.

  15. CRISPR/Cas9—Advancing Orthopoxvirus Genome Editing for Vaccine and Vector Development

    Science.gov (United States)

    Okoli, Arinze; Okeke, Malachy I.; Tryland, Morten; Moens, Ugo

    2018-01-01

    The clustered regularly interspaced short palindromic repeat (CRISPR)/associated protein 9 (Cas9) technology is revolutionizing genome editing approaches. Its high efficiency, specificity, versatility, flexibility, simplicity and low cost have made the CRISPR/Cas9 system preferable to other guided site-specific nuclease-based systems such as TALENs (Transcription Activator-like Effector Nucleases) and ZFNs (Zinc Finger Nucleases) in genome editing of viruses. CRISPR/Cas9 is presently being applied in constructing viral mutants, preventing virus infections, eradicating proviral DNA, and inhibiting viral replication in infected cells. The successful adaptation of CRISPR/Cas9 to editing the genome of Vaccinia virus paves the way for its application in editing other vaccine/vector-relevant orthopoxvirus (OPXV) strains. Thus, CRISPR/Cas9 can be used to resolve some of the major hindrances to the development of OPXV-based recombinant vaccines and vectors, including sub-optimal immunogenicity; transgene and genome instability; reversion of attenuation; potential of spread of transgenes to wildtype strains and close contacts, which are important biosafety and risk assessment considerations. In this article, we review the published literature on the application of CRISPR/Cas9 in virus genome editing and discuss the potentials of CRISPR/Cas9 in advancing OPXV-based recombinant vaccines and vectors. We also discuss the application of CRISPR/Cas9 in combating viruses of clinical relevance, the limitations of CRISPR/Cas9 and the current strategies to overcome them. PMID:29361752

  16. Multiple mechanisms for CRISPR-Cas inhibition by anti-CRISPR proteins.

    Science.gov (United States)

    Bondy-Denomy, Joseph; Garcia, Bianca; Strum, Scott; Du, Mingjian; Rollins, MaryClare F; Hidalgo-Reyes, Yurima; Wiedenheft, Blake; Maxwell, Karen L; Davidson, Alan R

    2015-10-01

    The battle for survival between bacteria and the viruses that infect them (phages) has led to the evolution of many bacterial defence systems and phage-encoded antagonists of these systems. Clustered regularly interspaced short palindromic repeats (CRISPR) and the CRISPR-associated (cas) genes comprise an adaptive immune system that is one of the most widespread means by which bacteria defend themselves against phages. We identified the first examples of proteins produced by phages that inhibit a CRISPR-Cas system. Here we performed biochemical and in vivo investigations of three of these anti-CRISPR proteins, and show that each inhibits CRISPR-Cas activity through a distinct mechanism. Two block the DNA-binding activity of the CRISPR-Cas complex, yet do this by interacting with different protein subunits, and using steric or non-steric modes of inhibition. The third anti-CRISPR protein operates by binding to the Cas3 helicase-nuclease and preventing its recruitment to the DNA-bound CRISPR-Cas complex. In vivo, this anti-CRISPR can convert the CRISPR-Cas system into a transcriptional repressor, providing the first example-to our knowledge-of modulation of CRISPR-Cas activity by a protein interactor. The diverse sequences and mechanisms of action of these anti-CRISPR proteins imply an independent evolution, and foreshadow the existence of other means by which proteins may alter CRISPR-Cas function.

  17. Selected papers from the 2nd IEEEE Nordic Circuits and Systems Conference (NorCAS), 2016

    DEFF Research Database (Denmark)

    Sparsø, Jens

    2018-01-01

    This special issue includes selected papers from the 2nd IEEEE Nordic Circuits and Systems Conference (NorCAS), held in Linköping, Sweden, October 24-25, 2016. The IEEE NorCAS conference is the main circuits and systems event of the Nordic and Baltic countries representing both academia and the e......This special issue includes selected papers from the 2nd IEEEE Nordic Circuits and Systems Conference (NorCAS), held in Linköping, Sweden, October 24-25, 2016. The IEEE NorCAS conference is the main circuits and systems event of the Nordic and Baltic countries representing both academia...

  18. Diagnostic étiologique du diabète insipide central: à propos de 41 cas

    Science.gov (United States)

    Chaker, Fatma; Chihaoui, Melika; Yazidi, Meriem; Slimane, Hedia

    2016-01-01

    La survenue d'un syndrome polyuro-polydipsiqueavec des urines hypotoniques nécessite une stratégie diagnostique rigoureuse. Le but de cette étude était d’étudier les modalités de diagnostic du diabète insipide central. A travers une étude rétrospective de 41 cas de diabète insipide central(DIC) colligés au service d'Endocrinologie à l'hôpital de la Rabta de Tunis, allant de l'année 1990 à l'an 2013, nous avons relevé les circonstances de découverte du DIC, les anomalies du bilan anté-hypophysaire etde l'imagerie hypophysaire. Le DIC était post opératoire chez 20 patients. La diurèse moyenne de 24 heures était significativement plus élevée chez les patients ayant un DIC en dehors d'un contexte chirurgical. L’épreuve de restriction hydrique était concluante chez tous les patients qui en ont bénéficié. En dehors d'un contexte neurochirurgical, les causes infiltratives étaient retrouvées chez 6 patientset les causes tumorales chez 6 patients. Le DIC était associé à une selle turcique vide dans 1 cas et idiopathique chez 3 malades. L'imagerie par résonnance magnétique hypothalamo-hypophysaire et le bilan anté-hypophysaire sont systématiques en dehors d'un contexte de chirurgie hypophysaire et d'une polydipsie primaire évidente. PMID:27642481

  19. CRISPR-Cas9-Edited Site Sequencing (CRES-Seq): An Efficient and High-Throughput Method for the Selection of CRISPR-Cas9-Edited Clones.

    Science.gov (United States)

    Veeranagouda, Yaligara; Debono-Lagneaux, Delphine; Fournet, Hamida; Thill, Gilbert; Didier, Michel

    2018-01-16

    The emergence of clustered regularly interspaced short palindromic repeats-Cas9 (CRISPR-Cas9) gene editing systems has enabled the creation of specific mutants at low cost, in a short time and with high efficiency, in eukaryotic cells. Since a CRISPR-Cas9 system typically creates an array of mutations in targeted sites, a successful gene editing project requires careful selection of edited clones. This process can be very challenging, especially when working with multiallelic genes and/or polyploid cells (such as cancer and plants cells). Here we described a next-generation sequencing method called CRISPR-Cas9 Edited Site Sequencing (CRES-Seq) for the efficient and high-throughput screening of CRISPR-Cas9-edited clones. CRES-Seq facilitates the precise genotyping up to 96 CRISPR-Cas9-edited sites (CRES) in a single MiniSeq (Illumina) run with an approximate sequencing cost of $6/clone. CRES-Seq is particularly useful when multiple genes are simultaneously targeted by CRISPR-Cas9, and also for screening of clones generated from multiallelic genes/polyploid cells. © 2018 by John Wiley & Sons, Inc. Copyright © 2018 John Wiley & Sons, Inc.

  20. Cas5d Protein Processes Pre-crRNA and Assembles into a Cascade-like Interference Complex in Subtype I-C/Dvulg CRISPR-Cas System

    Energy Technology Data Exchange (ETDEWEB)

    Nam, Ki Hyun; Haitjema, Charles; Liu, Xueqi; Ding, Fran; Wang, Hongwei; DeLisa, Matthew P.; Ke, Ailong (Yale); (Cornell); (Tsinghua)

    2012-10-10

    Clustered regularly interspaced short palindromic repeats (CRISPRs), together with an operon of CRISPR-associated (Cas) proteins, form an RNA-based prokaryotic immune system against exogenous genetic elements. Cas5 family proteins are found in several type I CRISPR-Cas systems. Here, we report the molecular function of subtype I-C/Dvulg Cas5d from Bacillus halodurans. We show that Cas5d cleaves pre-crRNA into unit length by recognizing both the hairpin structure and the 3 single stranded sequence in the CRISPR repeat region. Cas5d structure reveals a ferredoxin domain-based architecture and a catalytic triad formed by Y46, K116, and H117 residues. We further show that after pre-crRNA processing, Cas5d assembles with crRNA, Csd1, and Csd2 proteins to form a multi-sub-unit interference complex similar to Escherichia coli Cascade (CRISPR-associated complex for antiviral defense) in architecture. Our results suggest that formation of a crRNA-presenting Cascade-like complex is likely a common theme among type I CRISPR subtypes.