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Sample records for psychology cas dr

  1. 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.

  2. 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 ...

  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. Large Customers (DR Sellers)

    Energy Technology Data Exchange (ETDEWEB)

    Kiliccot, Sila [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2011-10-25

    State of the large customers for demand response integration of solar and wind into electric grid; openADR; CAISO; DR as a pseudo generation; commercial and industrial DR strategies; California regulations

  5. A Tribute to Dr. Willy Lens

    Directory of Open Access Journals (Sweden)

    Maarten Vansteenkiste

    2016-07-01

    Full Text Available Dr. Willy Lens, born on December 10th, 1943, passed away on August 29th, 2014. With his passing, the motivation community has lost a seminal member, a mentor, and a friend. Dr. Lens – a Fellow of the Association for Psychological Science and Founding Fellow of the American Educational Research Association – made fundamental contributions to the study of motivation both through his own work and through his caring and thoughtful mentorship of a large community of scholars. With this tribute, we want to honor Dr. Willy Lens’ significance to psychology and education as well as his positive influence, both personally and professionally, on the lives of dozens of scholars. With his contagious enthusiasm and caring mentorship, Willy was an example for our academic community and with this tribute we express our gratitude for the privilege to have collaborated with him.

  6. Galande, Dr Sanjeev

    Indian Academy of Sciences (India)

    Elected: 2010 Section: General Biology. Galande, Dr Sanjeev Ph.D. (IISc). Date of birth: 20 September 1967. Specialization: Epigenetics, Chromatin Biology, Gene Regulation, Genomics and Proteomics Address: Centre for Excellence in Epigenetics, Indian Institute of Science Education, & Research, Dr Homi Bhabha Road, ...

  7. Drømmejobbet

    DEFF Research Database (Denmark)

    Harrebye, Silas

    2012-01-01

    Medarbejdere vil i fremtiden også kunne arbejde, mens de sover. Virksomheder tilbyder snart deres ansatte interne kurser i ‘lucid dreaming’. Disse giver mulighed for, at man i sine drømme bliver bevidst om, at man drømmer og således kan manipulere dem. Det skal nu udnyttes. Management...

  8. Thiagarajan, Dr Pazhamaneri Subramaniam

    Indian Academy of Sciences (India)

    Elected: 1995 Section: Mathematical Sciences. Thiagarajan, Dr Pazhamaneri Subramaniam Ph.D. (Rice), FNASc. Date of birth: 9 November 1948. Specialization: Distributed Probabilistic Systems, Hybrid Systems and Computational Systems Biology Address: Laboratory of System Pharmacology, Harvard Medical School, ...

  9. Mishra, Dr A C

    Indian Academy of Sciences (India)

    Elected: 2009 Section: Medicine. Mishra, Dr A C . Ph.D. (Pune), FNA. Date of birth: 1 July 1950. Specialization: Human Viral Infection & Zoonotic Diseases, Public Health Address: Director, Interactive Research School of Health Affairs, Bharati Vidyapeeth University, ...

  10. Hazarika, Dr Nabajit

    Indian Academy of Sciences (India)

    Hazarika, Dr Nabajit Ph.D. (Tezpur). Date of birth: 17 January 1986. Specialization: Remote Sensing, GIS Applications, Fluvial Geomorphology, Landuse Landcover Studies Address: Dept. of Environmental Science, Nagaland University, Lumami 798 627, Nagaland Contact: Residence: 94354 81256, 97066 71256

  11. Gaia DR2 documentation

    Science.gov (United States)

    van Leeuwen, F.; de Bruijne, J. H. J.; Arenou, F.; Bakker, J.; Blomme, R.; Busso, G.; Cacciari, C.; Castañeda, J.; Cellino, A.; Clotet, M.; Comoretto, G.; Eyer, L.; González-Núñez, J.; Guy, L.; Hambly, N.; Hobbs, D.; van Leeuwen, M.; Luri, X.; Manteiga, M.; Pourbaix, D.; Roegiers, T.; Salgado, J.; Sartoretti, P.; Tanga, P.; Ulla, A.; Utrilla Molina, E.; Abreu, A.; Altmann, M.; Andrae, R.; Antoja, T.; Audard, M.; Babusiaux, C.; Bailer-Jones, C. A. L.; Barache, C.; Bastian, U.; Beck, M.; Berthier, J.; Bianchi, L.; Biermann, M.; Bombrun, A.; Bossini, D.; Breddels, M.; Brown, A. G. A.; Busonero, D.; Butkevich, A.; Cantat-Gaudin, T.; Carrasco, J. M.; Cheek, N.; Clementini, G.; Creevey, O.; Crowley, C.; David, M.; Davidson, M.; De Angeli, F.; De Ridder, J.; Delbò, M.; Dell'Oro, A.; Diakité, S.; Distefano, E.; Drimmel, R.; Durán, J.; Evans, D. W.; Fabricius, C.; Fabrizio, M.; Fernández-Hernández, J.; Findeisen, K.; Fleitas, J.; Fouesneau, M.; Galluccio, L.; Gracia-Abril, G.; Guerra, R.; Gutiérrez-Sánchez, R.; Helmi, A.; Hernandez, J.; Holl, B.; Hutton, A.; Jean-Antoine-Piccolo, A.; Jevardat de Fombelle, G.; Joliet, E.; Jordi, C.; Juhász, Á.; Klioner, S.; Löffler, W.; Lammers, U.; Lanzafame, A.; Lebzelter, T.; Leclerc, N.; Lecoeur-Taïbi, I.; Lindegren, L.; Marinoni, S.; Marrese, P. M.; Mary, N.; Massari, D.; Messineo, R.; Michalik, D.; Mignard, F.; Molinaro, R.; Molnár, L.; Montegriffo, P.; Mora, A.; Mowlavi, N.; Muinonen, K.; Muraveva, T.; Nienartowicz, K.; Ordenovic, C.; Pancino, E.; Panem, C.; Pauwels, T.; Petit, J.; Plachy, E.; Portell, J.; Racero, E.; Regibo, S.; Reylé, C.; Rimoldini, L.; Ripepi, V.; Riva, A.; Robichon, N.; Robin, A.; Roelens, M.; Romero-Gómez, M.; Sarro, L.; Seabroke, G.; Segovia, J. C.; Siddiqui, H.; Smart, R.; Smith, K.; Sordo, R.; Soria, S.; Spoto, F.; Stephenson, C.; Turon, C.; Vallenari, A.; Veljanoski, J.; Voutsinas, S.

    2018-04-01

    The second Gaia data release, Gaia DR2, encompasses astrometry, photometry, radial velocities, astrophysical parameters (stellar effective temperature, extinction, reddening, radius, and luminosity), and variability information plus astrometry and photometry for a sample of pre-selected bodies in the solar system. The data collected during the first 22 months of the nominal, five-year mission have been processed by the Gaia Data Processing and Analysis Consortium (DPAC), resulting into this second data release. A summary of the release properties is provided in Gaia Collaboration et al. (2018b). The overall scientific validation of the data is described in Arenou et al. (2018). Background information on the mission and the spacecraft can be found in Gaia Collaboration et al. (2016), with a more detailed presentation of the Radial Velocity Spectrometer (RVS) in Cropper et al. (2018). In addition, Gaia DR2 is accompanied by various, dedicated papers that describe the processing and validation of the various data products. Four more Gaia Collaboration papers present a glimpse of the scientific richness of the data. In addition to this set of refereed publications, this documentation provides a detailed, complete overview of the processing and validation of the Gaia DR2 data. Gaia data, from both Gaia DR1 and Gaia DR2, can be retrieved from the Gaia archive, which is accessible from https://archives.esac.esa.int/gaia. The archive also provides various tutorials on data access and data queries plus an integrated data model (i.e., description of the various fields in the data tables). In addition, Luri et al. (2018) provide concrete advice on how to deal with Gaia astrometry, with recommendations on how best to estimate distances from parallaxes. The Gaia archive features an enhanced visualisation service which can be used for quick initial explorations of the entire Gaia DR2 data set. Pre-computed cross matches between Gaia DR2 and a selected set of large surveys are

  12. Dr Math at your service

    CSIR Research Space (South Africa)

    Butgereit, L

    2012-10-01

    Full Text Available In this presentation the author explains how the Dr Math service works; how tutors are recruited to act as Dr Math; and how school pupils can reach Dr Math for help with their mathematics homework....

  13. 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.

  14. Dr Pugh: a poisoner?

    Science.gov (United States)

    Paull, J D; Morris, G M

    2012-07-01

    On 16 February 1845 the Reverend W. H. Browne, rector of St John's Church in Launceston, Van Diemen's Land, wrote in his journal, "My dear Wife died very suddenly almost immediately after and in consequence of taking a preparation of Hyd. Cyan. Acid prepared & supplied by Dr Pugh". This journal entry raises a number of questions. Was Dr Pugh treating a condition which he thought merited that treatment or was it a ghastly mistake? Was Caroline Browne suffering from pulmonary tuberculosis? Was hydrocyanic acid an accepted treatment at that time? Did Mrs Browne take the wrong dose? Was an incorrect concentration of the drug prepared by Dr Pugh? Did he use the wrong pharmacopoeia in preparing the hydrocyanic acid? Why was there no inquest? Only some of these questions can be answered.

  15. The DR-2 project

    DEFF Research Database (Denmark)

    Ølgaard, Povl Lebeck

    2003-01-01

    state of the reactor and to determine, which radionuclides remain where in the reactor in what amounts. The first part of the reactor to be investigated was the reactor tank. The lids at the reactor top wereremoved, air samples taken and smear test made in the tank. Then the control rods, the magnet....... At the start of the project the activity in DR-2 was about 45-50 GBq. Now it is about 5-10 GBq. Based on the results of the DR-2 project it is believed that the reactor can readily bedismantled and decommissioned....

  16. 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

  17. Gupta, Dr Chhitar Mal

    Indian Academy of Sciences (India)

    Gupta, Dr Chhitar Mal Ph.D. (Agra), FNA, FNASc, FAMS, FTWAS Council Service: 1998-2000. Date of birth: 1 September 1944. Specialization: Membrane Biology, Bio-organic Chemistry and Molecular Biophysics Address: Distinguished Professor and Infosys Chair, Institute of Bioinformatics & Applied Biotechnology, Room ...

  18. Mohanty, Dr Debasisa

    Indian Academy of Sciences (India)

    Home; Fellowship. Fellow Profile. Elected: 2012 Section: General Biology. Mohanty, Dr Debasisa Ph.D. (IISc), FNASc, FNA. Date of birth: 30 November 1966. Specialization: Bioinformatics, Computational & Structural Biology, Biophysics Address: National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110 067, ...

  19. Bal, Dr Dattatreya Vaman

    Indian Academy of Sciences (India)

    Home; Fellowship. Fellow Profile. Elected: 1943 Section: Animal Sciences. Bal, Dr Dattatreya Vaman Ph.D. (Liverpool). Date of birth: 25 August 1905. Date of death: 1 April 1999. Specialization: Marine Zoology, Oceanography. Fisheries and Aquaculture Last known address: 104, Swaroop Complex, Karve Road, Pune 411 ...

  20. Banerjee, Dr Srikumar

    Indian Academy of Sciences (India)

    Fellow Profile. Elected: 1990 Section: Engineering & Technology. Banerjee, Dr Srikumar Ph.D. (IIT, Kharagpur), FNA, FNAE, FNASc, FTWAS Council Service: 2007-12; Vice-President: 2010-12. Date of birth: 25 April 1946. Specialization: Materials Science, Physical Metallurgy, Phase Transformations, Nuclear Fuel Cycle, ...

  1. Drømmebilleder

    DEFF Research Database (Denmark)

    Fausing, Bent

    2014-01-01

    Bogen beskriver i en række intense analyser forbindelsen mellem ydre og indre billeder: altså mellem de moderne mediers billedverden og drømmens og erindringens indre billeder. I fokus for undersøgelsen er desuden kønnet, altså hvordan billeder viser, omformer eller skjuler kønnet, 'det andet', s...

  2. Agrewala, Dr Javed Naim

    Indian Academy of Sciences (India)

    Agrewala, Dr Javed Naim Ph.D. (Agra), FNA, FNASc. Date of birth: 14 May 1961. Specialization: Immunology, Vaccine, Drug Discovery Address: Chief Scientist, Immunology Laboratory, Institute of Microbial Technology, Sector 39A, Chandigarh 160 036, U.T.. Contact: Office: (0172) 666 5261. Residence: (0172) 666 5514

  3. Anil, Dr Arga Chandrashekar

    Indian Academy of Sciences (India)

    Home; Fellowship. Fellow Profile. Elected: 2015 Section: Earth & Planetary Sciences. Anil, Dr Arga Chandrashekar Ph.D. (Karnatak). Date of birth: 23 January 1959. Specialization: Biological Oceanography, Marine Ecology, Marine Biology Address: Chief Scientist, National Institute of Oceanography, Dona Paula 403 004, ...

  4. Prakash, Dr Vishweshwaraiah

    Indian Academy of Sciences (India)

    Prakash, Dr Vishweshwaraiah Ph.D. (Mysore), FNASc, FNAE, FRSC,FNAAS. Date of birth: 23 November 1951. Specialization: S&T Policy, Physical Biochemistry, Chemistry of Macromolecules, Biophysics of Proteins, Enzymes & Thermodynamics, Food Chemistry, Nutrition, Food Biotechnology and Food Science Address: ...

  5. Salunke, Dr Dinakar Mashnu

    Indian Academy of Sciences (India)

    Fellow Profile. Elected: 2001 Section: General Biology. Salunke, Dr Dinakar Mashnu Ph.D. (IISc), FNASc, FNA, FTWAS. Date of birth: 1 July 1955. Specialization: Structural Biology, Macromolecular Crystallography and Immunology Address: Director, International Centre for Genetic Engineering, & Biotechnology, Aruna Asaf ...

  6. Paranjpe, Dr Pramod Anand

    Indian Academy of Sciences (India)

    Elected: 1975 Section: Engineering & Technology. Paranjpe, Dr Pramod Anand D.Sc. Tech. (ETH Zurich). Date of birth: 1 April 1934. Specialization: Turbomachinery and Jet Propulsion Systems Address: 'Bahaar', 5, Hindustan Estate, Road No. 13, Kalyaninagar, Pune 411 006, Maharashtra Contact: Residence: (020) 2668 ...

  7. Bhawalkar, Dr Dilip Devidas

    Indian Academy of Sciences (India)

    Fellow Profile. Elected: 1986 Section: Physics. Bhawalkar, Dr Dilip Devidas Ph.D. (Southampton), FNA, FNASc. Date of birth: 16 October 1940. Specialization: Lasers and laser Instrumentation Address: 26, Paramanu Nagar, Indore 452 013, M.P.. Contact: Office: (0731) 232 2707. Residence: (0731) 232 0031. Mobile: 93032 ...

  8. Babu, Dr Cherukuri Raghavendra

    Indian Academy of Sciences (India)

    Fellow Profile. Elected: 1990 Section: Plant Sciences. Babu, Dr Cherukuri Raghavendra D.Phil. (Calcutta). Date of birth: 30 June 1940. Specialization: Biosystematics, Ecology and Population Genetics Address: Professor Emeritus, CEMDE, School of Environmental Studies, University of Delhi, Delhi 110 007, U.T.. Contact:

  9. Brahm Prakash, Dr

    Indian Academy of Sciences (India)

    Home; Fellowship. Fellow Profile. Elected: 1972 Section: Engineering & Technology. Brahm Prakash, Dr Ph.D. (Panjab), FNA 1974-76. Date of birth: 21 August 1912. Date of death: 3 January 1984. Specialization: Metallurgy. YouTube; Twitter; Facebook; Blog ...

  10. Budhani, Dr Ramesh Chandra

    Indian Academy of Sciences (India)

    Budhani, Dr Ramesh Chandra Ph.D. (IIT, Delhi), FNASc, FNA. Date of birth: 3 February 1955. Specialization: Renewable Energy, Nanoscale Systems, Experimental Condensed Matter Physics, Superconductivity and Magnetism Address: Department of Physics, Lasers & Photonics, Indian Institute of Technology, Kanpur 208 ...

  11. Ghosh, Dr Pushpito Kumar

    Indian Academy of Sciences (India)

    Home; Fellowship. Fellow Profile. Elected: 2010 Section: Chemistry. Ghosh, Dr Pushpito Kumar Ph.D. (Princeton). Date of birth: 29 May 1954. Specialization: Processes Research, Water Purification, Renewable Energy, R&D Management Address: A-604, Punit Park, Plot No. 182/C, Sector 17, Merol, Navi Mumbai 400 706, ...

  12. Varadarajan, Dr Srinivasan

    Indian Academy of Sciences (India)

    Elected: 1972 Section: Chemistry. Varadarajan, Dr Srinivasan Ph.D. (Delhi and Cantab), D.Sc. (h.c.), D.Litt. (h.c.), FNA, FNAE, FTWAS Council Service:1974-88; Vice-President: 1977-79; President: 1980-82. Date of birth: 31 March 1928. Specialization: Organic & Biological Chemistry, Molecular Biology, Engineering Design ...

  13. Brahmayya Sastry, Dr Podila

    Indian Academy of Sciences (India)

    Elected: 1978 Section: Medicine. Brahmayya Sastry, Dr Podila Ph.D. (McGill). Date of birth: 24 May 1913. Date of death: 28 May 1993. Specialization: Physiology, Neurophysiology and Placental Physiology Last known address: Sitaramanilayam, Plot No. 9, Doctors Co-Operative Housing Colony, Waltair, Visakhapatnam ...

  14. Majumdar, Dr Subeer Suhash

    Indian Academy of Sciences (India)

    Fellow Profile. Elected: 2014 Section: Animal Sciences. Majumdar, Dr Subeer Suhash Ph.D. (nagpur), FNA, FNASc. Date of birth: 21 May 1961. Specialization: Animal Biotechnology, Transgenic Animals, Endocrinology Address: Director, National Institute of Animal Biotechnology, Gopan Pally, Hyderabad 500 046, A.P.

  15. Sirsat, Dr Satyavati Motiram

    Indian Academy of Sciences (India)

    Sirsat, Dr Satyavati Motiram Ph.D. (Mumbai). Date of birth: 7 October 1925. Date of death: 10 July 2010. Specialization: Medical Research (Cancer) & Ultrastructural Pathology and Hospice Care of the Dying Last known address: Bhagirathi Sadan, 17th Road, Khar, Mumbai 400 052. YouTube · Twitter · Facebook · Blog ...

  16. Nandicoori, Dr Vinay Kumar

    Indian Academy of Sciences (India)

    Home; Fellowship. Fellow Profile. Elected: 2018 Section: General Biology. Nandicoori, Dr Vinay Kumar Ph.D. (IISc), FNASc. Date of birth: 1 March 1969. Specialization: Molecular & Cellular Biology, Cell Signalling, Cell Biology Address: National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110 067, U.T.; Contact ...

  17. Mukhopadhyay, Dr Amitabha

    Indian Academy of Sciences (India)

    Fellow Profile. Elected: 2010 Section: General Biology. Mukhopadhyay, Dr Amitabha Ph.D. (Jadavpur), FNASc, FNA. Date of birth: 5 February 1959. Specialization: Cell Biology, Host-Pathogen Interactions, Drug Delivery Address: Staff Scientist VII, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110 067, ...

  18. Gangal, Dr Sharad Vishwanath

    Indian Academy of Sciences (India)

    Gangal, Dr Sharad Vishwanath Ph.D. (Mumbai), FNASc. Date of birth: 2 May 1937. Specialization: Allergy, Immunology and Biochemistry Address: Lakshmi Niwas, Opp. Santoshi Mata Temple (B Cabin), Sane Guruji Path, Naupada, Thane 400 602, Maharashtra Contact: Residence: (022) 2537 6961. Mobile: 93249 24307

  19. Chitnis, Dr Chetan Eknath

    Indian Academy of Sciences (India)

    Home; Fellowship. Fellow Profile. Elected: 2009 Section: Medicine. Chitnis, Dr Chetan Eknath Ph.D. (UC, Berkeley), FNA. Date of birth: 3 April 1961. Specialization: Molecular Parasitology, Vaccine Development for Malaria and Molecular & Cell Biology Address: Head, Malaria Parasite Biology & Vaccine, Institut Pasteur, 28, ...

  20. Mukhopadhyay, Dr Sangita

    Indian Academy of Sciences (India)

    Elected: 2013 Section: Medicine. Mukhopadhyay, Dr Sangita Ph.D. (Utkal), FNASc. Date of birth: 1 January 1966. Specialization: Immunology, Cell Signalling, Communicable Diseases Address: Group Leader, Molecular Cell Biology, Centre for DNA Fingerprinting & Diagnostics, Nampally, Hyderabad 500 001, A.P.. Contact ...

  1. Bhandari, Dr Nita

    Indian Academy of Sciences (India)

    Elected: 2015 Section: Medicine. Bhandari, Dr Nita Ph.D. (JNU), FAMS. Date of birth: 9 November 1955. Specialization: Nutrition-Infection Interaction, Child Health, Nutritional Interventions, Clinical Evaluation of Vaccine Address: President & Director, Centre for Health R&D Society for Applied Studies, 45, Kalu Sarai, New ...

  2. Nageswara Rao, Dr Gullapalli

    Indian Academy of Sciences (India)

    Nageswara Rao, Dr Gullapalli M.D. (Opthal.) (AIIMS), FAMS, FACS, FRCS, FNASc. Date of birth: 1 September 1945. Specialization: Cornea, Community Eye Health and Eye Care Policy & Planning Address: Distinguished Chair of Eye Health, LV Prasad Eye Institute, LV Prasad Marg, Banjara Hills, Hyderabad 500 034, A.P.

  3. Chandrasekaran, Dr Chidambara

    Indian Academy of Sciences (India)

    Fellow Profile. Elected: 1945 Section: Mathematical Sciences. Chandrasekaran, Dr Chidambara Ph.D. (London) 1962-64. Date of birth: 30 October 1911. Date of death: 4 January 2000. Specialization: Statistics, Public Health and Demography Last known address: 'Sri Kripa', 79/3, Benson Cross Road, Bengaluru 560 046.

  4. Chandrashekar, Dr Tavarekere Kalliah

    Indian Academy of Sciences (India)

    Fellow Profile. Elected: 2000 Section: Chemistry. Chandrashekar, Dr Tavarekere Kalliah Ph.D. (IISc), FNASc, FNA, FTWAS Council Service: 2013-15. Date of birth: 1 January 1956. Specialization: Bio-inorganic Chemistry, Synthetic Inorganic Chemistry and Catalysis Address: Senior Professor, School of Chemical Sciences, ...

  5. Watve, Dr Milind Gajanan

    Indian Academy of Sciences (India)

    Date of birth: 12 December 1957. Specialization: Wildlife Ecology & Animal Cognition, Evolutionary Biology, Computational Biology and Microbial Diversity Address: Professor, Biology, Indian Institute of Science Education & Research, Dr Homi Bhabha Road, Pashan, Pune 411 008, Maharashtra Contact: Office: (020) 2590 ...

  6. Gangal, Dr Sudha Gajanan

    Indian Academy of Sciences (India)

    Gangal, Dr Sudha Gajanan Ph.D. (Mumbai), FNA Council Service: 1995-97. Date of birth: 25 August 1934. Specialization: Cancer & Basic Immunology, Cell Biology and Genetic Diseases Address: 4, Mahavishnu Apartments, Dahanukar Colony A, Kothrud, Pune 411 029, Maharashtra Contact: Residence: (020) 2538 4382, ...

  7. Amarjit Singh, Dr

    Indian Academy of Sciences (India)

    Home; Fellowship. Fellow Profile. Elected: 1974 Section: Engineering & Technology. Amarjit Singh, Dr Ph.D. (Harvard). Date of birth: 19 November 1924. Specialization: Millimeter Wave Tubes, Microwave Tubes and Microwave Electronics Address: 12, Auburn Court, Vernon Hills, IL 60061, USA Contact: Residence: ...

  8. Chandy, Dr Mammen

    Indian Academy of Sciences (India)

    Home; Fellowship. Fellow Profile. Elected: 2008 Section: Medicine. Chandy, Dr Mammen MD (Madras), FRACP, FRCPA. Date of birth: 30 August 1949. Specialization: Hematology, Bone Marrow Transplantation and Molecular Genetics of Blood Diseases Address: Director, Tata Memorial Centre, 14, Major Arterial Road, ...

  9. Thakur, Dr Vikram Chandra

    Indian Academy of Sciences (India)

    Home; Fellowship. Fellow Profile. Elected: 1991 Section: Earth & Planetary Sciences. Thakur, Dr Vikram Chandra Ph.D. (London). Date of birth: 15 January 1940. Specialization: Structural Geology, Tectonics of Himalayan Geology and Active Tectonics Address: 9/12 (Lane 9), Ashirwad Eclave, Dehra Dun 248 001, ...

  10. Shivaji, Dr Sisinthy

    Indian Academy of Sciences (India)

    Home; Fellowship. Fellow Profile. Elected: 2011 Section: Animal Sciences. Shivaji, Dr Sisinthy Ph.D. (Delhi), FNASc. Date of birth: 17 June 1950. Specialization: Anti-Microbial Resistance, Gut Microbiome, Eye Disease, Conservation Biology, Mammalian Sperm Function, Bacterial Biodiversity of Cold Habitats, Cold ...

  11. Dikshit, Dr Madhu

    Indian Academy of Sciences (India)

    Home; Fellowship. Fellow Profile. Elected: 2000 Section: Medicine. Dikshit, Dr Madhu Ph.D. (Kanpur), FNASc, FNA Council Service: 2016. Date of birth: 21 November 1957. Specialization: Redox Biology, Cardiovascular Pharmacology, Molecular Pharmacology, Neutrophiles and Nitric Oxide Synthase Address: Department ...

  12. Chaddah, Dr Praveen

    Indian Academy of Sciences (India)

    Home; Fellowship. Fellow Profile. Elected: 1993 Section: Physics. Chaddah, Dr Praveen Ph.D. (Mumbai), FNA, FNASc. Date of birth: 20 December 1951. Specialization: Superconductivity, Low Temperature Physics and Phase Transitions Address: Flat 702, Block 24, Heritage City, MG Road (near Metro Station), Gurgaon ...

  13. Sengupta, Dr Sagar

    Indian Academy of Sciences (India)

    Sengupta, Dr Sagar Ph.D. (IISc), FNA, FNASc. Date of birth: 23 June 1968. Specialization: Cancer Biology, Cell Signalling, Mytochondrial Biology Address: National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110 067, U.T.. Contact: Office: (011) 2670 3786. Residence: (0124) 422 7107. Mobile: 93131 05470

  14. Sharma, Dr Ram Swaroop

    Indian Academy of Sciences (India)

    Home; Fellowship. Fellow Profile. Elected: 1989 Section: Earth & Planetary Sciences. Sharma, Dr Ram Swaroop Ph.D. (Basel), FNA. Date of birth: 10 July 1937. Specialization: Metamorphic Petrology, Mineralogy and Precambrian Geology Address: 70/36, Pratapnagar, Sector 7, Sanganer (RHB), Jaipur 302 033, Rajasthan

  15. Shastry, Dr B Sriram

    Indian Academy of Sciences (India)

    Shastry, Dr B Sriram Ph.D. (Mumbai), FNA, FNASc, FTWAS. Date of birth: 26 November 1950. Specialization: Strongly-Correlated Fermi Systems, Quantum Integrable Systems Address: Distinguished Professor, Department of Physics, University of California, Santa Cruz, CA 95064, USA Contact: Office: (+1-831) 459 5849

  16. Dr Satish R. Shetye

    Indian Academy of Sciences (India)

    Elected: 1992 Section: Earth & Planetary Sciences. Shetye, Dr Satish Ramnath Ph.D. (Washington), FNA, FNASc. Council Service: 1998-2003. Date of birth: 25 October 1950. Specialization: Physical Oceanography Address: Vice Chancellor, Goa University, Taleigao Plateau 403 206, Goa Contact: Office: (0832) 651 9001

  17. Valluri, Dr Sitaram Rao

    Indian Academy of Sciences (India)

    Home; Fellowship. Fellow Profile. Elected: 1971 Section: Engineering & Technology. Valluri, Dr Sitaram Rao Ph.D. (Caltech). Date of birth: 25 June 1924. Specialization: Metal Fatigue Address: 'Prashanthi', 659, 100 Feet Road, Indiranagar, Bengaluru 560 038, Karnataka Contact: Residence: (080) 2525 8294. YouTube ...

  18. Authikesavalu, Dr Munisamy

    Indian Academy of Sciences (India)

    Home; Fellowship. Fellow Profile. Elected: 1948 Section: Medicine. Authikesavalu, Dr Munisamy MBBS (Madras), MS (Minneapolis), FRCS. Date of birth: 16 August 1906. Date of death: 22 September 1973. Specialization: Experimental Surgery, Ophthalmology, Otolaryngology Last known address: 5-C, Lavelle Cross Road, ...

  19. Sharma, Dr Surendra Kumar

    Indian Academy of Sciences (India)

    Elected: 2010 Section: Medicine. Sharma, Dr Surendra Kumar Ph.D. (AIIMS), MD (PGIMER, Chandigarh), FNASc, FNA. Date of birth: 22 February 1951. Specialization: Environmental Medicine, Infectious Diseases, Internal Medicine, Pulmonary & Critical Care and Sleep Medicine Address: B-5/3, B Block, Sector 13, RK ...

  20. Jameel, Dr Shahid

    Indian Academy of Sciences (India)

    Jameel, Dr Shahid Ph.D. (Washington State Univ.), FNASc, FNA. Date of birth: 8 August 1957. Specialization: Molecular Biology and Molecular Virology Address: Chief Executive Officer, The Wellcome Trust/DBT India Alliance, 8-2-684/3/K/19, Kaushik Society, Road NO. 12, Banjara Hills, Hyderabad 500 034, A.P.. Contact:

  1. Santhanam, Dr Vaidyanathaswamy

    Indian Academy of Sciences (India)

    Elected: 1974 Section: Plant Sciences. Santhanam, Dr Vaidyanathaswamy Ph.D. (Madras). Date of birth: 31 July 1925. Specialization: Plant Breeding & Genetics, Research Management and Cotton Development Address: 'Shri Abhirami', 107, Venkataswamy Road West, R S Puram Post, Coimbatore 641 002, T.N.. Contact:

  2. Shivanna, Dr Kundaranahalli Ramalingaiah

    Indian Academy of Sciences (India)

    Elected: 1985 Section: Plant Sciences. Shivanna, Dr Kundaranahalli Ramalingaiah Ph.D. (Delhi), FNA, FNAAS, FNASc. Date of birth: 30 June 1940. Specialization: Pollen Biology, Reproductive Ecology and Conservation Biology Address: Odekar Farms, Nandihalli, via Thovinakere, Tumkur 572 138, Karnataka Contact:

  3. Barua, Dr Asok Kumar

    Indian Academy of Sciences (India)

    Elected: 1987 Section: Physics. Barua, Dr Asok Kumar Ph.D. (Calcutta). Date of birth: 1 July 1936. Specialization: Solid State Materials, Thin Film Technology and Thin Film Solar Cells Address: Honorary Emeritus Professor, Indian Institute of Engineering Science & Technology, Shibpur, Howrah 711 103, W.B.. Contact:

  4. Jena, Dr Prafulla Kumar

    Indian Academy of Sciences (India)

    Jena, Dr Prafulla Kumar Ph.D. (Utkal). Date of birth: 27 December 1931. Specialization: Extractive Metallurgy, Mineral Processing, Environmental Engineering and Materials Processing Address: Chairman, Institute of Advance Technology and Environmental Studies, 80A-831A Lewis Road, Bhubaneswar 751 002, Orissa

  5. David, Dr Joy Caesarina

    Indian Academy of Sciences (India)

    Home; Fellowship. Fellow Profile. Elected: 1982 Section: Medicine. David, Dr Joy Caesarina M.B.B.S., M.S. (Madras). Date of birth: 3 May 1927. Date of death: 20 April 2004. Specialization: Neuropharmacology Last known address: 292, 4th Main, 1st Block, Koramangala, Bengaluru 560 034. YouTube; Twitter; Facebook ...

  6. Chandy, Dr Jacob

    Indian Academy of Sciences (India)

    Elected: 1961 Section: Medicine. Chandy, Dr Jacob MBBS (Madras), FRCS (c) Council Service: 1962-70. Date of birth: 23 January 1910. Date of death: 23 June 2007. Specialization: Neurology, Neurosurgery and Medical Education Last known address: Paarra, Matteethra, Kottayam 686 004. YouTube; Twitter; Facebook ...

  7. Mishra, Dr Rakesh K

    Indian Academy of Sciences (India)

    Mishra, Dr Rakesh K Ph.D. (Allahabad), FNASc, FNA. Date of birth: 14 April 1961. Specialization: Genomics, Chromatin, Epigenetics Address: Director, Centre for Cellular & Molecular Biology, Uppal Road, Hyderabad 500 007, A.P.. Contact: Office: (040) 2719 2600. Residence: (040) 2720 6400. Mobile: 94419 02188

  8. Ranganathan, Dr Darshan

    Indian Academy of Sciences (India)

    Elected: 1991 Section: Chemistry. Ranganathan, Dr Darshan Ph.D. (Delhi), FNA. Date of birth: 4 June 1941. Date of death: 4 June 2001. Specialization: Organic Chemistry, Bio-Organic Chemistry and Supramolecular Chemistry Last known address: Scientist, Indian Institue of Chemical, Technology, Uppal Road, Hyderabad ...

  9. Panda, Dr Subrat Kumar

    Indian Academy of Sciences (India)

    Panda, Dr Subrat Kumar M.B.B.S. (Utkal), M.D. (Path.) (AIIMS), FNA. Date of birth: 18 November 1954. Specialization: Liver Pathology, Viral Hepatitis and Molecular Biology/Virology Address: Professor, Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110 029, U.T.. Contact:

  10. Gurjar, Dr Mukund Keshao

    Indian Academy of Sciences (India)

    Gurjar, Dr Mukund Keshao Ph.D. (Nagpur and London), FNASc. Date of birth: 28 August 1952. Specialization: Carbohydrate Chemistry and Synthetic Organic Chemistry Address: Director, R&D, Emcure Pharmaceuticals Limited, P2, ITBT Park Phase II, Hinjwadi, Pune 411 057, Maharashtra Contact: Office: (020) 3982 1350, ...

  11. Kulkarni, Dr Mohan Gopalkrishna

    Indian Academy of Sciences (India)

    Elected: 1996 Section: Engineering & Technology. Kulkarni, Dr Mohan Gopalkrishna Ph.D. (Mumbai), FNAE. Date of birth: 14 November 1950. Specialization: Polymer Science & Engineering, Intellectual Property Address: Emeritus Scientist, Unit for R&D of Information Products, Tapovan, NCL Campus, Pashan Road, Pune ...

  12. Sethunathan, Dr Nambrattil

    Indian Academy of Sciences (India)

    Fellow Profile. Elected: 1986 Section: Plant Sciences. Sethunathan, Dr Nambrattil Ph.D. (Madras), FNA, FNAAS, FNASc. Date of birth: 2 June 1937. Specialization: Environmental Microbiology Address: Flat No. 103, Ushodaya Apartments, Sri Venkateswara Officers' Colony, Ramakrishnapuram, Secunderabad 500 056, A.P.

  13. Parnaik, Dr Veena Krishnaji

    Indian Academy of Sciences (India)

    Elected: 2008 Section: Animal Sciences. Parnaik, Dr Veena Krishnaji Ph.D. (Ohio State), FNA. Date of birth: 22 August 1953. Specialization: Cell Biology, Molecular Biology, Lamins and Nuclear Organisation Address: INSA Senior Scientist, Centre for Cellular & Molecular Biology, Uppal Road, Hyderabad 500 007, A.P.

  14. Sengupta, Dr Sagar

    Indian Academy of Sciences (India)

    Fellow Profile. Elected: 2017 Section: General Biology. Sengupta, Dr Sagar Ph.D. (IISc), FNA, FNASc. Date of birth: 23 June 1968. Specialization: Cancer Biology, Cell Signalling, Mytochondrial Biology Address: National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110 067, U.T.. Contact: Office: (011) 2670 3786

  15. Basu, Dr Sandip Kumar

    Indian Academy of Sciences (India)

    Fellow Profile. Elected: 1992 Section: General Biology. Basu, Dr Sandip Kumar Ph.D. (Calcutta), FNASc, FNA, FTWAS Council Service: 1995-97. Date of birth: 1 January 1944. Specialization: Cell Biology, Molecular Biology and Microbial Genetics Address: FD-426, Sector 3, Bidhan Nagar, Kolkata 700 106, W.B.. Contact:

  16. Adhya, Dr Samit

    Indian Academy of Sciences (India)

    Elected: 1999 Section: General Biology. Adhya, Dr Samit Ph.D. (New York), FNA. Date of birth: 29 September 1953. Specialization: Mitochondrial Biology, Molecular Genetics of Parasites, Intracellular RNA Trafficking and DNA Diagnostics Address: CSIR Emeritus Scientist, Indian Inst. of Chemical Biology, 4, Raja S.C. ...

  17. Apte, Dr Shree Kumar

    Indian Academy of Sciences (India)

    Elected: 2008 Section: General Biology. Apte, Dr Shree Kumar Ph.D. (Gujarat), FNA, FNASc, FNAAS. Date of birth: 18 October 1952. Specialization: Molecular Biology & Biotechnology, Physiology and Stress Biology of Bacteria & Plants Address: Emeritus Professor, Homi Bhabha National Institute, Anushakti Nagar, ...

  18. Mukerji, Dr Mitali

    Indian Academy of Sciences (India)

    Elected: 2014 Section: Medicine. Mukerji, Dr Mitali Ph.D. (IISc). Date of birth: 13 November 1967. Specialization: Functional Genomics, Population Genomics, Ayurgenomics Address: Sr Principal Scientist, Genomics & Molecualr Medicine, Institute of Genomics & Integrative Biology, Sukhdev Vihar, Mathura Road, New Delhi ...

  19. 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

  20. 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

  1. 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

  2. Gaia DR1 documentation

    Science.gov (United States)

    van Leeuwen, F.; de Bruijne, J. H. J.; Arenou, F.; Comoretto, G.; Eyer, L.; Farras Casas, M.; Hambly, N.; Hobbs, D.; Salgado, J.; Utrilla Molina, E.; Vogt, S.; van Leeuwen, M.; Abreu, A.; Altmann, M.; Andrei, A.; Babusiaux, C.; Bastian, U.; Biermann, M.; Blanco-Cuaresma, S.; Bombrun, A.; Borrachero, R.; Brown, A. G. A.; Busonero, D.; Busso, G.; Butkevich, A.; Cantat-Gaudin, T.; Carrasco, J. M.; Castañeda, J.; Charnas, J.; Cheek, N.; Clementini, G.; Crowley, C.; Cuypers, J.; Davidson, M.; De Angeli, F.; De Ridder, J.; Evans, D.; Fabricius, C.; Findeisen, K.; Fleitas, J. M.; Gracia, G.; Guerra, R.; Guy, L.; Helmi, A.; Hernandez, J.; Holl, B.; Hutton, A.; Klioner, S.; Lammers, U.; Lecoeur-Taïbi, I.; Lindegren, L.; Luri, X.; Marinoni, S.; Marrese, P.; Messineo, R.; Michalik, D.; Mignard, F.; Montegriffo, P.; Mora, A.; Mowlavi, N.; Nienartowicz, K.; Pancino, E.; Panem, C.; Portell, J.; Rimoldini, L.; Riva, A.; Robin, A.; Siddiqui, H.; Smart, R.; Sordo, R.; Soria, S.; Turon, C.; Vallenari, A.; Voss, H.

    2017-12-01

    We present the first Gaia data release, Gaia DR1, consisting of astrometry and photometry for over 1 billion sources brighter than magnitude 20.7 in the white-light photometric band G of Gaia. The Gaia Data Processing and Analysis Consortium (DPAC) processed the raw measurements collected with the Gaia instruments during the first 14 months of the mission, and turned these into an astrometric and photometric catalogue. Gaia DR1 consists of three parts: an astrometric data set which contains the positions, parallaxes, and mean proper motions for about 2 million of the brightest stars in common with the Hipparcos and Tycho-2 catalogues (the primary astrometric data set) and the positions for an additional 1.1 billion sources (the secondary astrometric data set). The primary set forms the realisation of the Tycho-Gaia Astrometric Solution (TGAS). The second part of Gaia DR1 is the photometric data set, which contains the mean G-band magnitudes for all sources. The third part consists of the G-band light curves and the characteristics of 3000 Cepheid and RR Lyrae stars observed at high cadence around the south ecliptic pole. The positions and proper motions in the astrometric data set are given in a reference frame that is aligned with the International Celestial Reference Frame (ICRF) to better than 0.1 mas at epoch J2015.0, and non-rotating with respect to the ICRF to within 0.03 mas yr^-1. For the primary astrometric data set, the typical standard error for the positions and parallaxes is about 0.3 mas, while for the proper motions the typical standard error is about 1 mas yr^-1. Whereas it has been suggested in Gaia Collaboration et al. (2016a) that a systematic component of ∼0.3 mas should be 'added' (in quadrature) to the parallax uncertainties, Brown (2017) clarifies that reported parallax standard errors already include local systematics as a result of the calibration of the TGAS parallax uncertainties by comparison to Hipparcos parallaxes. For the subset of

  3. Dr. Sheehan on Running.

    Science.gov (United States)

    Sheehan, George A.

    This book is both a personal and technical account of the experience of running by a heart specialist who began a running program at the age of 45. In its seventeen chapters, there is information presented on the spiritual, psychological, and physiological results of running; treatment of athletic injuries resulting from running; effects of diet…

  4. Drømmefabrikken

    Directory of Open Access Journals (Sweden)

    Paulo Affonso Grisolli

    1994-09-01

    Full Text Available Som mangeårig producent af telenovelaer både i Brasilien og Portugal, kender Grisolli alle sider af telenovelaen: Novelaen som de fattiges drøm om rigdom og succes, novelaen som et redskab i TV-kanalernes kamp om seerne, som exportvare, som glansbillede under det brasillianske dik- tatur, som industriprodukt og som politisk igangsætter. I denne artikel be- skriver Grisolli sine erfaringer med gode og dårlige sider af telenovela- fascinationen i Latinamerika og præsenterer en ny genre, som er på vej frem i Brasilien, mini-serien. Artiklen er Grisollis foredrag på Folkekirkens Nødhjælps Konference om TV og Video i Latinamerika, november 1992.

  5. 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...

  6. From Mxit to Dr Math

    CSIR Research Space (South Africa)

    Botha, Adèle

    2013-02-01

    Full Text Available In 2007, Laurie Butgereit, a researcher at the CSIR Meraka Institute, started to use Mxit as a communication channel to tutor her son in mathematics. Her son and a number of his friends logged in, and Dr Math was born. At the inception of Dr Math...

  7. How Dr. Pierce Promoted Himself

    Data.gov (United States)

    Department of the Interior — This article is about Dr. Raymond V Pierce who owned St. Vincent Island before it became a refuge. The doctor painted advertisements for his famous “Woman’s Tonic”...

  8. Dr Stanislaw Huskowski, Mayor of Wroclaw, Poland

    CERN Multimedia

    Patrice Loïez

    2002-01-01

    Dr Stanislaw Huskowski, Mayor of Wroclaw, Poland visiting the ATLAS magnet assembly hall, building 180. From l to r: Mr Carlo Lamprecht, State Councillor, Dr Stanislaw Huskowski and Dr Peter Jenni, ATLAS Spokesperson

  9. Dr Stanislaw Huskowski, Mayor of Wroclaw, Poland

    CERN Multimedia

    Patrice Loïez

    2002-01-01

    Dr Stanislaw Huskowski, Mayor of Wroclaw, Poland visiting the ATLAS magnet assembly hall, building 180 with Mr Carlo Lamprecht, State Councillor, Dr Stanislaw Huskowski and Dr Peter Jenni, ATLAS Spokesperson

  10. Dr Luigi Orlando, Dr Sergio Ceccuzzi, Dr. Armando Sbrana, Europa Metalli, Italy, Dr Albert Scherger, Member of KM Europa Metal AG, Osnabr ck, Germany, Prof. Filippo Menzinger, Scientific Attaché, Permanent Mission of Italy in Geneva

    CERN Multimedia

    Patrice Loïez

    2001-01-01

    Photo 01: Dr Lyn Evans and Dr Luigi Orlando Photo 04: L. to r.: Dr Lyn Evans, Dr Luigi Orlando, Prof. Luciano Maiani and Prof. Filippo Menzinger Photo 06: L. to r.: Prof. Philippo Menzinger, Dr Armando Sbrana, Prof. Luciano Maiani, Dr Albert Scherger, Dr Lyn Evans, Dr Luigi Orlando, Dr Sergio Ceccuzzi, visiting the LHC superconducting magnet test hall, SM18

  11. Tribute to Dr Jacques Rogge

    DEFF Research Database (Denmark)

    Bourgois, Jan G; Dumortier, Jasmien; Callewaert, Margot

    2017-01-01

    'A tribute to Dr J. Rogge' aims to systematically review muscle activity and muscle fatigue during sustained submaximal quasi-isometric knee extension exercise (hiking) related to Olympic dinghy sailing as a tribute to Dr Rogge's merits in the world of sports. Dr Jacques Rogge is not only...... of invasive needle electromyography (EMG) during a specific sailing technique (hiking) on a self-constructed sailing ergometer. Hiking is a bilateral and multi-joint submaximal quasi-isometric movement which dinghy sailors use to optimize boat speed and to prevent the boat from capsizing. Large stresses...... are generated in the anterior muscles that cross the knee and hip joint, mainly employing the quadriceps at an intensity of 30-40% maximal voluntary contraction (MVC), sometimes exceeding 100% MVC. Better sailing level is partially determined by a lower rate of neuromuscular fatigue during hiking and for ≈60...

  12. Ali, Dr Moizuddin Abdul Salim

    Indian Academy of Sciences (India)

    ... Section: Animal Sciences. Ali, Dr Moizuddin Abdul Salim D.Sc. (Andhra), D.Sc. (h.c.), FNA. Date of birth: 12 November 1896. Date of death: 20 June 1987. Specialization: Ecology, Zoogeography, Nature Conservation, Ornithology Last known address: No. 46, Pali Hill, Bombay 400 050. YouTube; Twitter; Facebook; Blog ...

  13. DR. MIKA MAJALE MEMORIAL LECTURE

    African Journals Online (AJOL)

    He had four children Irene Majale,. Prof. Mike Majale (Architect) Victoria Majale Ojiambo and Chris Majale. Dr. Majale died on 21st April 1978. As an orthopaedic Surgeon he worked at Kenyatta. National Hospital (KNH), Kabete Orthopaedic Unit and. Armed Forces Memorial Hospital. He did not do any private practice.

  14. Murty, Dr Thutupalli Gopala Krishna

    Indian Academy of Sciences (India)

    Elected: 2002 Section: Engineering & Technology. Murty, Dr Thutupalli Gopala Krishna Ph.D. (Adelaide). Date of birth: 11 February 1944. Specialization: Optical Engineering, Thin Film Technology, Electro-Optical Instrumentation and Atmospheric Science Technologies Address: 848, 8th B Main, 17th Cross, ISRO Layout, ...

  15. Dr. John Marburger visits DESY

    CERN Multimedia

    2003-01-01

    Dr. John Marburger, Director of the United States Office of Science and Technology Policy, visited the research center DESY in Hamburg. The American physicist wanted to inform himself about the status of the TESLA X-ray laser and the TESLA linear collider as well as the international collaboration at DESY (1/2 page).

  16. 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.

  17. 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...

  18. Sproglige drømmerier

    DEFF Research Database (Denmark)

    Farø, Ken Joensen

    2015-01-01

    blev tidligere brugt i Danmarks Radio som pausesignal, afspillet på en spilledåse. Ak ja, det var dengang. Gå ind på nettet og lyt til den, hvis du ikke kender melodien. Det er national kulturarv. Mange bevingede ord indeholder en form af ”drøm(me)”, fx Martin Luther Kings ”I have a Dream”. Eller...

  19. Discursive Psychology

    NARCIS (Netherlands)

    Molder, te H.F.M.

    2016-01-01

    Discursive psychology examines how psychological issues are made relevant and put to use in everyday talk. Unlike traditional psychological perspectives, discursive psychology does not approach the question of what psychology comprises and explains from an analyst's perspective. Instead, the focus

  20. FOREWORD: Dr Trevor J Hicks Dr Trevor J Hicks

    Science.gov (United States)

    Goossens, Darren

    2009-03-01

    This issue of Journal of Physics: Condensed Matter has been assembled to recognize the valuable contribution of Dr Trevor J Hicks to the field of neutron scattering and magnetism. Trevor began his study of magnetism as a PhD student at Monash University in Melbourne in the early 1960s, working with Professor Jack Smith. From the very beginning magnetism in alloys, and disordered systems in general, became a key aspect of his career. After a postdoctoral position at Harwell working with Dr Graeme Low Trevor returned to Australia and took up a position with Monash. He soon became a key figure in developing the capability for neutron scattering using the HIFAR reactor at the Australian Atomic Energy Commission, now the Australian Nuclear Science and Technology Organisation, ANSTO. The instrumentation was always developed to further his studies of magnetism. The development of polarization analysis measurements of diffuse magnetic scattering, first using iron filters and then his own design of supermirror benders for beam polarization, took place through the 1970s, 1980s and into the 1990s. Throughout this time, Trevor mentored a series of PhD students and postdoctoral fellows, many of whom have contributed to this issue (and, indeed, guest edited it). As befits a scientist and university academic for whom teaching has always been important, Trevor has not only created a strong body of significant research, he has also made a major contribution to preparing several generations of neutron scattering scientists, and this issue reflects that. When I approached Journal of Physics: Condensed Matter with a proposal for an issue in honour of Trevor, the response was immediate and positive. It is with great pleasure that I present the result of that proposal. The great diversity of the content, all centred on neutron scattering and magnetism, reflects the breadth of Trevor's own career and of the scientists with whom he has interacted. Finally, I would like to make some

  1. In Memoriam: Dr. Frank John Fenner

    Centers for Disease Control (CDC) Podcasts

    This podcast reflects on one of the greatest pioneers in virology, Dr. Frank John Fenner. Dr. Frederick Murphy, a member of EID's editorial board and the Institute of Medicine, and professor of Pathology at the University of Texas Medical Branch in Galveston, shares professional and personal stories of Dr. Frank Fenner.

  2. Interview with Dr Anna Matamala

    Directory of Open Access Journals (Sweden)

    Lucinea Marcelino Villela

    2016-09-01

    In this interview, which took place in June 2016, Dr Anna Matamala described some details about her long professional experience in Audiovisual Translation, especially in dubbing from English into Catalan, and we talked about many other things like her interest in lexicography, her point of view on some contemporary topics in Audiovisual Translation Studies: the use of technology, the relation between AVT and Accessibility Studies, AVT and Filmmaking fields, the importance of keeping in touch with other countries and even continents outside Europe, and she also gave some advice to the new generation of Translation students.

  3. Interview with Dr Anna Matamala

    Directory of Open Access Journals (Sweden)

    Lucinea Marcelino Villela

    2016-12-01

    Full Text Available In this interview, which took place in June 2016, Dr Anna Matamala described some details about her long professional experience in Audiovisual Translation, especially in dubbing from English into Catalan, and we talked about many other things like her interest in lexicography, her point of view on some contemporary topics in Audiovisual Translation Studies: the use of technology, the relation between AVT and Accessibility Studies, AVT and Filmmaking fields, the importance of keeping in touch with other countries and even continents outside Europe, and she also gave some advice to the new generation of Translation students.

  4. 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...

  5. Invisible Wounds of War: Recommendations for Addressing Psychological and Cognitive Injuries

    National Research Council Canada - National Science Library

    Tanielian, Terri

    2008-01-01

    My testimony will briefly discuss several recommendations for addressing the psychological and cognitive injuries among servicemembers returning from deployments to Operations Enduring Freedom and Iraqi Freedom. Dr...

  6. 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.

  7. 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.

  8. 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.

  9. [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.

  10. Application of ophthalmic ultrasonographyin DR

    Directory of Open Access Journals (Sweden)

    Ya-Ke Li

    2018-02-01

    Full Text Available AIM: To investigate the value of ultrasonography in diabetic retinopathy(DR. METHODS: Totally 103 cases(103 eyesof type 2 diabetes mellitus were selected from May 2015 to May 2017 in our hospital, there were 32 patients 32 eyes with non diabetic retinopathy(NDR, 40 patients 40 eyes with non proliferative diabetic retinopathy(NPDR, and 31 patients 31 eyes with proliferative diabetic retinopathy(PDR, 40 healthy volunteers(40 eyeswere selected as control group, the maximum systolic blood flow velocity(PSV, end diastolic velocity(EDVand resistance index(RIof the central retinal artery(CRA, posterior ciliary artery(PCAand ophthalmic artery(OAwere detected by color Doppler ultrasound. RESULTS: The difference of PSV, EDV and RI of CRA, PCA and OA in each group was statistically significant(PPPPCONCLUSION: Color Doppler ultrasound monitoring the hemodynamic changes of ocular blood vessels in diabetes can provide evidence for early detection of diabetic retinopathy.

  11. 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...

  12. In Memoriam: Dr. Frank John Fenner

    Centers for Disease Control (CDC) Podcasts

    2011-04-22

    This podcast reflects on one of the greatest pioneers in virology, Dr. Frank John Fenner. Dr. Frederick Murphy, a member of EID's editorial board and the Institute of Medicine, and professor of Pathology at the University of Texas Medical Branch in Galveston, shares professional and personal stories of Dr. Frank Fenner.  Created: 4/22/2011 by National Center for Emerging Zoonotic and Infectious Diseases (NCEZID).   Date Released: 4/26/2011.

  13. Dr. von Braun Briefing Walt Disney

    Science.gov (United States)

    1965-01-01

    Dr. von Braun began his association with Walt Disney in the 1950s when the rocket scientist appeared in three Disney television productions related to the exploration of space. Years later, Dr. von Braun invited Disney and his associates to tour the Marshall Space Flight Center (MSFC) in Huntsville, Alabama. This photograph is dated April 13, 1965. From left are R.J. Schwinghamer from the MSFC, Disney, B.J. Bernight, and Dr. von Braun.

  14. China's Investment Leade Dr, Alyce Su

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    @@ I. Professional Background Dr. Alyce Su specializes in investment managemeng, managing portfolios consisted of investment opportunities originated from China's growth and internationalization, both'outbound and inbound.

  15. 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...

  16. 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.

  17. 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...

  18. 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...

  19. 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. 

  20. Dr Valter Rukavina - amateur painter.

    Science.gov (United States)

    Glavocic, Daina

    2008-01-01

    In this essay Dr Valter Rukavina (Rijeka 1896-1972), excellent specialist in infectious diseases and professor of the Rijeka University School of Medicine, is presented as successful amateur painter. He had been refining his talent through relentless practice since the school days, complementing it with skills and advice from established painters he associated with. He favoured figurative, realistic and somewhat romantic expression for his themes such as coastal landscapes, marinas, Quarnero sceneries, still life in tempera or oil, and drawings in ink or sepia. Despite partial colour blindness, he successfully used colour. He featured in a number of group exhibitions such as that of amateur painters of Rijeka in 1950, of painters physicians of Yugoslavia (Zagreb, 1956), in the Second International Exhibition of Contemporary Art (Florence, 1964), exhibition of the Rijeka branch of the Croatian Association of Visual Artists (Belgrade, 1966), and the 1969 exhibition in Opatija. His native city hosted two one-man exhibitions, the first retrospective in 1971, while he was still alive, and the second posthumous in 2007, with a good selection of his life's work.

  1. 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

  2. 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.

  3. 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

  4. Gaia DR2 documentation Chapter 7: Variability

    Science.gov (United States)

    Eyer, L.; Guy, L.; Distefano, E.; Clementini, G.; Mowlavi, N.; Rimoldini, L.; Roelens, M.; Audard, M.; Holl, B.; Lanzafame, A.; Lebzelter, T.; Lecoeur-Taïbi, I.; Molnár, L.; Ripepi, V.; Sarro, L.; Jevardat de Fombelle, G.; Nienartowicz, K.; De Ridder, J.; Juhász, Á.; Molinaro, R.; Plachy, E.; Regibo, S.

    2018-04-01

    This chapter of the Gaia DR2 documentation describes the models and methods used on the 22 months of data to produce the Gaia variable star results for Gaia DR2. The variability processing and analysis was based mostly on the calibrated G and integrated BP and RP photometry. The variability analysis approach to the Gaia data has been described in Eyer et al. (2017), and the Gaia DR2 results are presented in Holl et al. (2018). Detailed methods on specific topics will be published in a number of separate articles. Variability behaviour in the colour magnitude diagram is presented in Gaia Collaboration et al. (2018c).

  5. An Interview with Dr. Walter Lear

    Directory of Open Access Journals (Sweden)

    The Editors

    2009-03-01

    Full Text Available In this issue of the English version of Social Medicine we are publishing the first of several pamphlets loaned to us by the US Health Activism History Collection. To introduce this collection we travelled to Philadelphia on June 18, 2008 to interview Dr. Walter J. Lear. Dr Lear, born in 1923, is the person responsible for the collection. In a wide-ranging interview in his home Dr. Lear discussed his personal background, the origins and purpose of the collection, the impact of the McCarthy period on the US health left, as well as his vision for the future.

  6. [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.

  7. Abd-Allah, Dr. Adel-Gamil

    African Journals Online (AJOL)

    Abd-Allah, Dr. Adel-Gamil. Vol 12, No 4 (2000) - Articles CORRELATION BETWEEN UTERINE ARTERY FLOW VELOCITY WAVEFORMS AND ENDOMETRIAL HISTOPATHOLOGY IN WOMEN WITH PERIMENOPAUSAL AND POSTMENOPAUSAL BLEEDING. Details. ISSN: 1110-5607. AJOL African Journals Online.

  8. Raghavarao, Dr Karumanchi Srisaila Mallikarjuna S

    Indian Academy of Sciences (India)

    Elected: 2014 Section: Engineering & Technology. Raghavarao, Dr Karumanchi Srisaila Mallikarjuna S Ph.D. (Mumbai), FNAE, FNAAS. Specialization: Food Engineering, Biotechnology Address: Chief Scientist, Department of Food Engineering, Central Food Technological Research Institute, Mysore 570 020, Karnataka

  9. Dr. Shi Hanzhang's Experience in Treating Andropathy

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ Dr. Shi Hanzhang (施汉章) of Dongzhimen Hospital affiliated to Beijing University of Traditional Chinese Medicine is experienced in both teaching and clinical practice, especially in treating andropathy, such as sexual disorder, infertility, and hyperplasia of the prostate. The author has the honour to follow him for study and really learned a lot from him. A brief introduction to Dr. Shi's way of thinking in treatment is as follows.

  10. Implementing Python for DrRacket

    OpenAIRE

    Ramos, Pedro Palma; Leitão, António Menezes

    2014-01-01

    The Python programming language is becoming increasingly popular in a variety of areas, most notably among novice programmers. On the other hand, Racket and other Scheme dialects are considered excellent vehicles for introducing Computer Science concepts. This paper presents an implementation of Python for Racket and the DrRacket IDE. This allows Python programmers to use Racket libraries and vice versa, as well as using DrRacket's pedagogic features. In particular, it allows architects and d...

  11. 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.

  12. 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

  13. Modulation of TRAIL resistance in colon carcinoma cells: Different contributions of DR4 and DR5

    International Nuclear Information System (INIS)

    Geelen, Caroline MM van; Pennarun, Bodvael; Le, Phuong TK; Vries, Elisabeth GE de; Jong, Steven de

    2011-01-01

    rhTRAIL is a therapeutic agent, derived from the TRAIL cytokine, which induces apoptosis in cancer cells by activating the membrane death receptors 4 and 5 (DR4 and DR5). Here, we investigated each receptor's contribution to rhTRAIL sensitivity and rhTRAIL resistance. We assessed whether agonistic DR4 or DR5 antibodies could be used to circumvent rhTRAIL resistance, alone or in combination with various chemotherapies. Our study was performed in an isogenic model comprised of the SW948 human colon carcinoma cell line and its rhTRAIL resistant sub-line SW948-TR. Effects of rhTRAIL and agonistic DR4/DR5 antibodies on cell viability were measured using MTT assays and identification of morphological changes characteristic of apoptosis, after acridine orange staining. Sensitivity to the different death receptor ligands was stimulated using pretreatment with the cytokine IFN-gamma and the proteasome inhibitor MG-132. To investigate the mechanisms underlying the changes in rhTRAIL sensitivity, alterations in expression levels of targets of interest were measured by Western blot analysis. Co-immunoprecipitation was used to determine the composition of the death-inducing signalling complex at the cell membrane. SW948 cells were sensitive to all three of the DR-targeting agents tested, although the agonistic DR5 antibody induced only weak caspase 8 cleavage and limited apoptosis. Surprisingly, agonistic DR4 and DR5 antibodies induced equivalent DISC formation and caspase 8 cleavage at the level of their individual receptors, suggesting impairment of further caspase 8 processing upon DR5 stimulation. SW948-TR cells were cross-resistant to all DR-targeting agents as a result of decreased caspase 8 expression levels. Caspase 8 protein expression was restored by MG-132 and IFN-gamma pretreatment, which also re-established sensitivity to rhTRAIL and agonistic DR4 antibody in SW948-TR. Surprisingly, MG-132 but not IFN-gamma could also increase DR5-mediated apoptosis in SW948

  14. Modulation of TRAIL resistance in colon carcinoma cells: Different contributions of DR4 and DR5

    Directory of Open Access Journals (Sweden)

    de Vries Elisabeth GE

    2011-01-01

    Full Text Available Abstract Background rhTRAIL is a therapeutic agent, derived from the TRAIL cytokine, which induces apoptosis in cancer cells by activating the membrane death receptors 4 and 5 (DR4 and DR5. Here, we investigated each receptor's contribution to rhTRAIL sensitivity and rhTRAIL resistance. We assessed whether agonistic DR4 or DR5 antibodies could be used to circumvent rhTRAIL resistance, alone or in combination with various chemotherapies. Methods Our study was performed in an isogenic model comprised of the SW948 human colon carcinoma cell line and its rhTRAIL resistant sub-line SW948-TR. Effects of rhTRAIL and agonistic DR4/DR5 antibodies on cell viability were measured using MTT assays and identification of morphological changes characteristic of apoptosis, after acridine orange staining. Sensitivity to the different death receptor ligands was stimulated using pretreatment with the cytokine IFN-gamma and the proteasome inhibitor MG-132. To investigate the mechanisms underlying the changes in rhTRAIL sensitivity, alterations in expression levels of targets of interest were measured by Western blot analysis. Co-immunoprecipitation was used to determine the composition of the death-inducing signalling complex at the cell membrane. Results SW948 cells were sensitive to all three of the DR-targeting agents tested, although the agonistic DR5 antibody induced only weak caspase 8 cleavage and limited apoptosis. Surprisingly, agonistic DR4 and DR5 antibodies induced equivalent DISC formation and caspase 8 cleavage at the level of their individual receptors, suggesting impairment of further caspase 8 processing upon DR5 stimulation. SW948-TR cells were cross-resistant to all DR-targeting agents as a result of decreased caspase 8 expression levels. Caspase 8 protein expression was restored by MG-132 and IFN-gamma pretreatment, which also re-established sensitivity to rhTRAIL and agonistic DR4 antibody in SW948-TR. Surprisingly, MG-132 but not IFN

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. 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

  20. 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

  1. 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...

  2. 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.

  3. Investigative psychology

    OpenAIRE

    Canter, David V.

    2010-01-01

    The domain of Investigative Psychology covers all aspects of psychology that are relevant to the conduct of criminal or civil investigations. Its focus is on the ways in which criminal activities may be examined and understood in order for the detection of crime to be effective and legal proceedings to be appropriate. As such Investigative Psychology is concerned with psychological input to the full range of issues that relate to the management, investigation and prosecution of crime

  4. Modulation of TRAIL resistance in colon carcinoma cells : Different contributions of DR4 and DR5

    NARCIS (Netherlands)

    van Geelen, Caroline M. M.; Pennarun, Bodvael; Le, Phuong T. K.; de Vries, Elisabeth G. E.; de Jong, Steven

    2011-01-01

    Background: rhTRAIL is a therapeutic agent, derived from the TRAIL cytokine, which induces apoptosis in cancer cells by activating the membrane death receptors 4 and 5 (DR4 and DR5). Here, we investigated each receptor's contribution to rhTRAIL sensitivity and rhTRAIL resistance. We assessed whether

  5. Dr. Wernher von Braun and Dr. Ernst Stuhlinger Sign Citizenship Certificates

    Science.gov (United States)

    1955-01-01

    The members of the Peenemuende team and their family members were awarded the United States citizenship on April 14, 1955. Pictured here is Dr. Ernst Stuhlinger (middle) and Dr. Wernher von Braun signing U.S. citizenship certificates. Martin Schilling is at left.

  6. CRISPR-Cas9, a tool to efficiently increase the development of recombinant African swine fever viruses.

    Science.gov (United States)

    Borca, Manuel V; Holinka, Lauren G; Berggren, Keith A; Gladue, Douglas P

    2018-02-16

    African swine fever virus (ASFV) causes a highly contagious disease called African swine fever. This disease is often lethal for domestic pigs, causing extensive losses for the swine industry. ASFV is a large and complex double stranded DNA virus. Currently there is no commercially available treatment or vaccine to prevent this devastating disease. Development of recombinant ASFV for producing live-attenuated vaccines or studying the involvement of specific genes in virus virulence has relied on the relatively rare event of homologous recombination in primary swine macrophages, causing difficulty to purify the recombinant virus from the wild-type parental ASFV. Here we present the use of the CRISPR-Cas9 gene editing system as a more robust and efficient system to produce recombinant ASFVs. Using CRISPR-Cas9 a recombinant virus was efficiently developed by deleting the non-essential gene 8-DR from the genome of the highly virulent field strain Georgia07 using swine macrophages as cell substrate.

  7. Dræb, dræb, dræb! Nej ... liiiige et øjeblik: De machiavelliske følelser i Game of Thrones

    DEFF Research Database (Denmark)

    Schubart, Rikke

    2013-01-01

    Blogindlæg om Machiavelliske følelser i HBO tv-serien Game of Thrones: "Dræb, dræb, dræb! Nej ... liiiige et øjeblik: De machiavelliske følelser i Game of Thrones"......Blogindlæg om Machiavelliske følelser i HBO tv-serien Game of Thrones: "Dræb, dræb, dræb! Nej ... liiiige et øjeblik: De machiavelliske følelser i Game of Thrones"...

  8. Positive Psychology

    Science.gov (United States)

    Peterson, Christopher

    2009-01-01

    Positive psychology is a deliberate correction to the focus of psychology on problems. Positive psychology does not deny the difficulties that people may experience but does suggest that sole attention to disorder leads to an incomplete view of the human condition. Positive psychologists concern themselves with four major topics: (1) positive…

  9. Kantian Psychologism

    NARCIS (Netherlands)

    Sperber, P.|info:eu-repo/dai/nl/377312894

    2017-01-01

    For more than a hundred years now, the dominant view amongst scholars has been that Kant's philosophy has nothing to do with psychology, or, at the very least, that psychology is inessential to Kant's philosophical project. In the early reception of Kant's work, however, psychology played a central

  10. [Dr. Atanasije Puljo: pioneer of Serbian dentistry].

    Science.gov (United States)

    Jovananović, Svetlana; Milovanović, Srdjan; Zagradjanin, Danica; Milovanović, Nebojša; Puzović, Dragana

    2012-01-01

    This paper describes the life and work of Dr. Atanasije Puljo (1878-1944). He was a volunteer in the Balkan wars, an active participant in the First World War; he was the first who noted the importance of team-work of a dentist and a surgeon in the care of jaw and facial injuries. He established primacy in this field, as he came up with this brilliant idea three years before other colleagues. His method of treatment of the upper jaw neglected fractures, called the Balkan method, was recognized worldwide. Dr. Puljo is the pioneer of dental radiology in Serbia, founder of the Odontology Clinic of the Medical Faculty and main supporter of the establishment of the School of Dentistry. Merits of Dr. Atanasije Puljo, medical practitioner with a broad knowledge in different fields, remain within the academic institution that was founded by this pioneer of dentistry in Serbia.

  11. Dr. David Syz, State Secretary for Economic Affairs, Switzerland

    CERN Multimedia

    Patrice Loïez

    2003-01-01

    Photo 01: Dr. David Syz (left) with Professor Roger Cashmore, Research Director for Collider Programmes.Photo 02: Dr. David Syz signing the VIP visitors' book, with Prof. Roger Cashmore.Photo 03: Dr. David Syz signing the VIP visitors' book.Photo 04: Handshake between Dr. David Syz (left) and Prof. Roger Cashmore.

  12. 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.

  13. Mathematical psychology.

    Science.gov (United States)

    Batchelder, William H

    2010-09-01

    Mathematical psychology is a sub-field of psychology that started in the 1950s and has continued to grow as an important contributor to formal psychological theory, especially in the cognitive areas of psychology such as learning, memory, classification, choice response time, decision making, attention, and problem solving. In addition, there are several scientific sub-areas that were originated by mathematical psychologists such as the foundations of measurement, stochastic memory models, and psychologically motivated reformulations of expected utility theory. Mathematical psychology does not include all uses of mathematics and statistics in psychology, and indeed there is a long history of such uses especially in the areas of perception and psychometrics. What is most unique about mathematical psychology is its approach to theory construction. While accepting the behaviorist dictum that the data in psychology must be observable and replicable, mathematical models are specified in terms of unobservable formal constructs that can predict detailed aspects of data across multiple experimental and natural settings. By now almost all the substantive areas of cognitive and experimental psychology have formal mathematical models and theories, and many of these are due to researchers that identify with mathematical psychology. Copyright © 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. Copyright © 2010 John Wiley & Sons, Ltd.

  14. Socioecological psychology.

    Science.gov (United States)

    Oishi, Shigehiro

    2014-01-01

    Socioecological psychology investigates humans' cognitive, emotional, and behavioral adaption to physical, interpersonal, economic, and political environments. This article summarizes three types of socioecological psychology research: (a) association studies that link an aspect of social ecology (e.g., population density) with psychology (e.g., prosocial behavior), (b) process studies that clarify why there is an association between social ecology and psychology (e.g., residential mobility → anxiety → familiarity seeking), and (c) niche construction studies that illuminate how psychological states give rise to the creation and maintenance of a social ecology (e.g., familiarity seeking → dominance of national chain stores). Socioecological psychology attempts to bring the objectivist perspective to psychological science, investigating how objective social and physical environments, not just perception and construal of the environments, affect one's thinking, feeling, and behaviors, as well as how people's thinking, feeling, and behaviors give rise to social and built environments.

  15. 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

  16. 2700-IJBCS-Article-Dr Matar Seck

    African Journals Online (AJOL)

    hp

    of Maytenus senegalensis in the management of sickle cell disease. © 2016 International ... En plus de l'anémie, la vaso-occlusion, résultant de la ... crises de douleur, de la fièvre et des douleurs ... vaso-occlusives dans la drépanocytose. Ces.

  17. Dr. Ding Hou 80 years young

    NARCIS (Netherlands)

    Baas, Pieter; Adema, Frits

    2001-01-01

    Eleven October 2001 is the 80th birthday of Dr. Ding Hou, much appreciated Honorary Staff Member of our Nationaal Herbarium Nederland. Time to reflect on the life and career of this modest but highly productive and talented botanist. Ding Hou was born in 1921 in Hsingkan, Kiangsi Province, China.

  18. DR and CR: Recent advances in technology

    International Nuclear Information System (INIS)

    Schaefer-Prokop, C.M.; De Boo, D.W.; Uffmann, M.; Prokop, M.

    2009-01-01

    After some initial reluctance, nowadays transition from conventional analogue-to-digital radiographic technique is realized in the vast majority of institutions. The eventual triumph of digital over conventional technique is related to its undoubted advantages with respect to image quality and improved image handling in the context of a picture archiving and communication system. CR represents the older system, which matured over decades and experienced some important recent improvements with respect to dose efficiency and work-flow efficiency that strengthened its position. It represents a very versatile, economically attractive system that is equally suited for integrated systems as well as for cassette-based imaging at the bedside. DR systems offer superb image quality and realistic options for dose reduction based on their high dose efficiency. While for a long time only integrated systems were on the market suited for a large patient throughput, also mobile DR systems became recently available. While for the next years, it is likely that DR and CR systems will coexist, the long term perspective of CR will depend on further innovations with respect to dose efficiency and signal-to-noise characteristics while for DR economical aspects and broader availability of mobile systems will play a role.

  19. Reminiscences by Dr. I.I. Rabi

    International Nuclear Information System (INIS)

    Rabi, I.I.

    1973-01-01

    Dr. I.I. Rabi, Professor of Physics, Columbia University, Nobel Laureate, adviser to presidents and an original member of the scientific advisory committees both of the United Nations and the IAEA, delivered the following address at the Salazar Atomic Centre, Mexico, in October 1972 he spoke on 'reminiscences from scientific advisory services to governments and international organizations'. (author)

  20. Confessions of a Dr Math tutor

    CSIR Research Space (South Africa)

    Butgereit, L

    2015-06-01

    Full Text Available Mathematics look different on a small 3-inch screen of an inexpensive cell phone when compared to a 3-meter whiteboard in a mathematics classroom. Dr Math uses cell phone or mobile data "chat" technologies to assist primary and secondary school...

  1. Stop words for “Dr Math”

    CSIR Research Space (South Africa)

    Butgereit, L

    2011-05-01

    Full Text Available “Dr Math” is a facility where primary and secondary school pupils can use MXit on their cell phones to get help with their mathematics homework. Pupils use an abbreviated “MXit lingo” leaving out most vowels and substituting various numerals...

  2. Dr. Francis Collins Is New NIH Director

    Science.gov (United States)

    ... Ph.D., a physician and geneticist, is the new Director of the National Institutes of Health (NIH), part of the U.S. Department of Health and Human Services. President Barack Obama nominated Dr. Collins, who served as Director of ...

  3. The great neurosis of Dr. Joseph Gerard.

    Science.gov (United States)

    Lefrère, Jean-Jacques; Rouillon, Frédéric

    2013-01-01

    The Great Neurosis, of Dr. Joseph Gerard, was published in 1889 in Paris. The book, intended for the general public, shows the different varieties of neuroses through picturesque and instructive examples. Its scientific and medical value is poor, but provides us with the various meanings of the word 'neurosis' in the late nineteenth century. Copyright © 2013 S. Karger AG, Basel.

  4. Dr. Andrew Foster: A Literature Review

    Science.gov (United States)

    Runnels, Joel

    2017-01-01

    Often compared to Laurent Clerc, Thomas Gallaudet, and Alexander Graham Bell, Dr. Andrew Foster was a deaf African American who founded 32 schools for the deaf in 13 African nations. The 60th anniversary of his arrival in Liberia and Ghana and the 30th anniversary of his tragic death in a Rwanda airplane accident both occur in 2017. Renewed…

  5. Chamber of Commerce reception for Dr. Lucas

    Science.gov (United States)

    1986-01-01

    Dr. William R. Lucas, Marshall's fourth Center Director (1974-1986), delivers a speech in front of a picture of the lunar landscape with Earth looming in the background while attending a Huntsville Chamber of Commerce reception honoring his achievements as Director of Marshall Space Flight Center (MSFC).

  6. In Memoriam Dr. J. H. Kern

    NARCIS (Netherlands)

    Kalkman, C.

    1974-01-01

    On 29 July 1974 dr. J. H. Kern died at the age of 70. At the occasion of his official retirement from the Rijksherbarium staff (January 1969) Van Steenis and Van Ooststroom gave due recognition to his achievements in tropical botany and to his share in the progress of the knowledge of the Dutch

  7. Underwater Gliders by Dr. Kevin Smith [video

    OpenAIRE

    Naval Postgraduate School Physics

    2015-01-01

    NPS Physics NPS Physics Research Projects Underwater glider research is currently underway in the physics department at the naval postgraduate in Monterey Ca. Dr. Kevin Smith is a specialist in underwater acoustics and sonar systems. He and his team are currently focused on autonomous underwater gliders and developing systems capable of detecting parameters in the ocean and listening for various sources of sound.

  8. 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...

  9. 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...

  10. 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.

  11. 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

  12. [Political psychology].

    Science.gov (United States)

    Resch, Mária; Bella, Tamás

    2013-04-21

    In Hungary one can mostly find references to the psychological processes of politics in the writings of publicists, public opinion pollsters, philosophers, social psychologists, and political analysts. It would be still important if not only legal scientists focusing on political institutions or sociologist-politologists concentrating on social structures could analyse the psychological aspects of political processes; but one could also do so through the application of the methods of political psychology. The authors review the history of political psychology, its position vis-à-vis other fields of science and the essential interfaces through which this field of science, which is still to be discovered in Hungary, connects to other social sciences. As far as its methodology comprising psycho-biographical analyses, questionnaire-based queries, cognitive mapping of interviews and statements are concerned, it is identical with the psychiatric tools of medical sciences. In the next part of this paper, the focus is shifted to the essence and contents of political psychology. Group dynamics properties, voters' attitudes, leaders' personalities and the behavioural patterns demonstrated by them in different political situations, authoritativeness, games, and charisma are all essential components of political psychology, which mostly analyses psychological-psychiatric processes and also involves medical sciences by relying on cognitive and behavioural sciences. This paper describes political psychology, which is basically part of social sciences, still, being an interdisciplinary science, has several ties to medical sciences through psychological and psychiatric aspects.

  13. Dr. von Braun and Dr. Stuhlinger With a Model of the Nuclear-Electric Vehicles

    Science.gov (United States)

    2004-01-01

    In this photo, taken at the Walt Disney Studios in California, Dr. Wernher von Braun and Dr. Ernst Stuhlinger are shown discussing the concepts of nuclear-electric spaceships designed to undertake the mission to the planet Mars. As a part of the Disney 'Tomorrowland' series on the exploration of space, the nuclear-electric vehicles were shown in the last three television films, entitled 'Mars and Beyond,' which first aired in December 1957.

  14. 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....

  15. 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....

  16. Decommissioning of DR 1, Final report

    International Nuclear Information System (INIS)

    Lauridsen, Kurt

    2006-01-01

    The report describes the decommissioning activities carried out at the 2kW homogeneous reactor DR 1 at Risoe National Laboratory. The decommissioning work took place from summer 2004 until late autumn 2005. The components with the highest activity, the core vessel the recombiner and the piping and valves connected to these, were dismantled first by Danish Decommissioning's own technicians. Demolition of the control rod house and the biological shield as well as the removal of the floor in the reactor hall was carried out by an external demolition contractor. The building was emptied and left for other use. Clearance measurements of the building showed that radionuclide concentrations were everywhere below the clearance limit set by the Danish nuclear regulatory authorities. Furthermore, measurements on the surrounding area showed that there was no contamination that could be attributed to the operation and decommissioning of DR 1. (au)

  17. Decommissioning of DR 1, Final report

    Energy Technology Data Exchange (ETDEWEB)

    Lauridsen, Kurt

    2006-01-15

    The report describes the decommissioning activities carried out at the 2kW homogeneous reactor DR 1 at Risoe National Laboratory. The decommissioning work took place from summer 2004 until late autumn 2005. The components with the highest activity, the core vessel the recombiner and the piping and valves connected to these, were dismantled first by Danish Decommissioning's own technicians. Demolition of the control rod house and the biological shield as well as the removal of the floor in the reactor hall was carried out by an external demolition contractor. The building was emptied and left for other use. Clearance measurements of the building showed that radionuclide concentrations were everywhere below the clearance limit set by the Danish nuclear regulatory authorities. Furthermore, measurements on the surrounding area showed that there was no contamination that could be attributed to the operation and decommissioning of DR 1. (au)

  18. Analysis of DR4 haplotypes in insulin dependent diabetes (IDD)

    International Nuclear Information System (INIS)

    Monos, D.S.; Radka, S.F.; Zmijewski, C.M.; Kamoun, M.

    1986-01-01

    Population studies indicate that HLA-DR4 is implicated in the susceptibility of IDD. However, biochemical characterization of the serologically defined DR4 haplotype from normal individuals revealed five DR4 and three DQW3 molecular forms. Hence, in this study, they investigated the heterogeneity of the DR4 haplotype, using B-lymphoblastoid cell lines (B-LCL) generated from patients with IDD and seropositive for DR4. Class II molecules, metabolically labeled with 35 S-methionine, were immunoprecipitated with monoclonal antibodies specific for DR(L243), DQ(N297), DQW3(IVD12) or DR and DQ(SG465) and analyzed by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). The isoelectrofocusing (IEF) conditions employed in this study allow representation only of the DR4 haplotype from either DR3/4 or DR4/4 cell lines. The analysis of six different DR4 haplotypes from seven IDD patients, revealed the presence of two DR4 β and two DQW3 β chains. Three of the six DR4 β haplotypes analyzed shared the same DR4 β chain and three others shared a different one. Additionally five of the six haplotypes shared a different one. Additionally five of the six haplotypes shared the same DQW3 β chain and only one was carrying a different one. Different combinations of the two DR4 and two DQW3 β chains constitute three distinct patterns of DR4 haplotypes. These results suggest the prevalence of a DQW3 β chain in the small sample of IDD patients studied. Studies of a large number of patients should clarify whether IDD is associated with unique variants of DR4 or DQW3 β chains

  19. Psychological behaviorism and behaviorizing psychology

    Science.gov (United States)

    Staats, Arthur W.

    1994-01-01

    Paradigmatic or psychological behaviorism (PB), in a four-decade history of development, has been shaped by its goal, the establishment of a behaviorism that can also serve as the approach in psychology (Watson's original goal). In the process, PB has become a new generation of behaviorism with abundant heuristic avenues for development in theory, philosophy, methodology, and research. Psychology has resources, purview and problem areas, and nascent developments of many kinds, gathered in chaotic diversity, needing unification (and other things) that cognitivism cannot provide. Behaviorism can, within PB's multilevel framework for connecting and advancing both psychology and behaviorism. PMID:22478175

  20. [Homage to Professor Dr. Nicasio Etchepareborda].

    Science.gov (United States)

    1998-11-01

    During a solemn academic act, de Main Classroom of the Facultad de Odontologia de Buenos Aires was named after Prof. Dr. Nicasio Etchepareborda. He has been the first professor at the Escuela de Odontologia and its organizer, after having obtained his Dentistry degree at the Dental School of Paris, in 1882. The new school was founded in 1891, and its activities began the following year.

  1. Discursive Psychology

    NARCIS (Netherlands)

    Molder, te H.

    2015-01-01

    Discursive psychology was established in the United Kingdom by the end of the 1980s, mainly in response to the dominant cognitivist approach in social psychology. While it borrowed notions from poststructuralism and sociology of science, it is most akin to conversation analysis. Discursive

  2. Psychological experiment

    NARCIS (Netherlands)

    Boven, Martijn; Emmanuel, Steven M.; McDonald, William; Stewart, Jon

    2015-01-01

    For Kierkegaard the ‘psychological experiment’ is a literary strategy. It enables him to dramatize an existential conflict in an experimental mode. Kierkegaard’s aim is to study the source of movement that animates the existing individual (this is the psychological part). However, he is not

  3. Rational Emotive Behavioural Therapy: The Evolution of a Revolution: Interview With Dr. Debbie Joffe Ellis, Work Partner and Wife of Dr. Albert Ellis, the Creator of REBT.

    Science.gov (United States)

    Ellis, Debbie Joffe; Rovira, Montse

    2015-02-01

    Recognized as one of the most influential thinkers and psychologists, Albert Ellis PhD (1913-2007) revolutionized Psychology when he created the first cognitive psychotherapy, Rational Emotive Behavioral Therapy. After he passed away, Dr. Debbie Joffe Ellis continues spreading his legacy around the world. Psychologist, lecturer, writer, trainer, she dedicates her life to disseminate REBT and extend it through different statements, from the social to the educational, from the academic to the clinical. In this interview, she goes through her own history and her husband's one, bringing us closer to understanding Albert Ellis as the leading figure in his field, and the oneness they experienced through their professional and personal relationship.

  4. 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.

  5. Coverage of Russian psychological contributions in American psychology textbooks.

    Science.gov (United States)

    Aleksandrova-Howell, Maria; Abramson, Charles I; Craig, David Philip Arthur

    2012-01-01

    Internationalizing psychology is an important component of current globalization trends. American textbooks on the history of psychology and introductory psychology were surveyed for the presence of historical and contemporary important Russian psychologists to assess the current status of Russian-American crossfertilization. Of a list of 97 important Russian psychologists, as determined by the editors of the Russian journal Methodology and History in Psychology, less than 22% are mentioned in the reviewed texts. The most common names were Pavlov, Luria, and Vygotsky. As the internet is arguably the single most important factor affecting the increase of international communication and dissemination of knowledge, we also searched for these 97 names on various websites, most notably Wikipedia and Google. Forty-one internet sites contained some amount of biographical information about Russian psychologists. On Wikipedia, 14 Russian psychologists had articles documenting biographical information. We also developed a rubric to determine the amount of information available on the internet for these psychologists and compared Wikipedia's mean score with various other websites. Wikipedia pages on average had a significantly higher score than the rest of the internet. Recommendations to improve Russian coverage in America are provided and include: (1) developing pages on Wikipedia and other virtual venues highlighting Russian contributions, (2) soliciting articles for US journals from Russian psychologists, and (3) incorporating Russian contributions in introductory and historical textbooks. We provide a partial bibliography of Russian contributions that can be used by authors of such textbooks. We would like to thank Dr Viktor Fedorovich Petrenko and Dr Igor Nikolaevich Karitsky from the journal Methodology and History of Psychology for supplying the names of the Russian psychologists. We would also like to express our appreciation to Robert García for reviewing and

  6. Gaia DR1 documentation Chapter 6: Variability

    Science.gov (United States)

    Eyer, L.; Rimoldini, L.; Guy, L.; Holl, B.; Clementini, G.; Cuypers, J.; Mowlavi, N.; Lecoeur-Taïbi, I.; De Ridder, J.; Charnas, J.; Nienartowicz, K.

    2017-12-01

    This chapter describes the photometric variability processing of the Gaia DR1 data. Coordination Unit 7 is responsible for the variability analysis of over a billion celestial sources. In particular the definition, design, development, validation and provision of a software package for the data processing of photometrically variable objects. Data Processing Centre Geneva (DPCG) responsibilities cover all issues related to the computational part of the CU7 analysis. These span: hardware provisioning, including selection, deployment and optimisation of suitable hardware, choosing and developing software architecture, defining data and scientific workflows as well as operational activities such as configuration management, data import, time series reconstruction, storage and processing handling, visualisation and data export. CU7/DPCG is also responsible for interaction with other DPCs and CUs, software and programming training for the CU7 members, scientific software quality control and management of software and data lifecycle. Details about the specific data treatment steps of the Gaia DR1 data products are found in Eyer et al. (2017) and are not repeated here. The variability content of the Gaia DR1 focusses on a subsample of Cepheids and RR Lyrae stars around the South ecliptic pole, showcasing the performance of the Gaia photometry with respect to variable objects.

  7. Words of gratitude to Dr. Michel Huguet

    International Nuclear Information System (INIS)

    Yoshikawa, Masaji

    2003-01-01

    It is impossible for the Japanese fusion community, in particular for those associated with the ITER Project,to hear about the retirement of Dr. Michel Huguet without a great amount of gratitude, recollections, warm feelings, and the inevitable sadness. He was a first-generation ITER EDA person. Three months after the signing of the ITER EDA Agreement in July 1992, he arrived at the Naka Joint Work Site as Deputy Director of the ITER Central Team and Head of the site and he stayed for more than ten years. The Naka site was for design and technical co-ordination in the areas of magnets, plasma control and heating, plant systems, buildings, etc. Dr. Huguet was considered a highly qualified person to fill the position, since he had been successful as Deputy Director in similar areas in the JET Joint Undertaking. During the ITER EDA he co-ordinated the R and D activities in areas for which the Naka Joint Work Site was responsible. These R and D results permitted the completion of the ITER design in the above areas under his supervision. We thank Dr. Huguet for his achievements and contributions to ITER. He played a crucial role in establishing the convincing scientific and technical basis for ITER implementation. This was only made possible by his broad abilities and his dedication to the cause of fusion in general and ITER in particular

  8. 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

  9. Treating Cataracts: Dr. Rachel Bishop's Top Tips for Your Eyes

    Science.gov (United States)

    ... please turn JavaScript on. Feature: Treating Cataracts Dr. Rachel Bishop's Top Tips for Your Eyes Past Issues / ... exams, a healthy lifestyle, and eye protection. Dr. Rachel Bishop, chief of consult services at the National ...

  10. Potensi dan Efektivitas Pemungutan Retribusi RSUD Dr. Agoesdjam Ketapang

    OpenAIRE

    B61110063, JAMALUDIN

    2014-01-01

    This study entitled Potential and Effectiveness of retribution collecting in RSUD Dr. Agoesdjam Ketapang which aims to identify and analyze the potential retribution of RSUD Dr . Agoesdjam and also to investigate and analyze the effectiveness of the retribution collecting in RSUD Dr. Agoesdjam . This study uses secondary data , from 2008 to 2012 that were obtained from the Regional Revenue Office of Ketapang and RSUD Dr. Agoesdjam Ketapang . The method of this study is descriptive. To analyz...

  11. HLA-DR expression and disease activity in ulcerative colitis

    DEFF Research Database (Denmark)

    Poulsen, L O; Elling, P; Sørensen, Flemming Brandt

    1986-01-01

    and 3 months later. The rectal epithelial cells were HLA-DR-positive in all patients at the first two examinations. After 3 months five patients had changed to an HLA-DR-negative stage, whereas the other seven patients remained HLA-DR-positive. Closer analyses showed that expression/nonexpression of HLA...

  12. 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.

  13. Award for Distinguished Contributions to the International Advancement of Psychology.

    Science.gov (United States)

    2017-12-01

    This award is given to individuals who have made sustained and enduring contributions to international cooperation and the advancement of knowledge in psychology. The 2017 recipient of the APA Award for Distinguished Contributions to the International Advancement of Psychology was selected by the 2016 Committee on International Relations in Psychology (CIRP). The members of the 2016 CIRP were Melissa Morgan Consoli, PhD, and Arpana G. Inman, PhD (Co-chairs); Rehman Abdulrehman, PhD; Gonzalo Bacigalupe, EdD; Frederic Bemak, EdD; Brigitte Khoury, PhD; Susan Nolan, PhD; Nancy Sidun, PsyD; and Danny Wedding, PhD. Dr. Morgan Consoli, Dr. Inman, Dr. Nolan, and Doctor Sidun were members of the subcommittee for the 2017 award. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  14. Dr. Yu Wang, Director, Natural Science Division, National Science Council, Taiwan

    CERN Document Server

    Patrice Loïez

    2001-01-01

    Photo 01: L. to r.: Dr. Philippe Bloch, CERN CMS ECAL Deputy Project Manager, Dr. Yu Wang, Dr. Etiennette Auffray, CERN, responsible of the CERN ECAL Regional Centre. Photo 02: L. to r.: Dr. Yu Wang, Dr. Philippe Bloch, Dr. Apollo GO, National Central University, Taiwan, Dr. Etiennette Auffray.

  15. Psychology and modern life challenges: the 2nd Middle East and North Africa Regional Conference of Psychology, Amman, Jordan, 2007.

    Science.gov (United States)

    Knowles, Michael; Sabourin, Michel

    2008-04-01

    The Second Middle East and North Africa Regional Conference of Psychology was held in Amman from 27 April - 1 May 2007 under the Royal Patronage of Her Majesty Queen Rania Al-Abdullah and the auspices of the International Union of Psychological Science, the International Association of Applied Psychology, and the International Association of Cross-Cultural Psychology. It was hosted by the Jordanian Psychological Association whose President was Dr. Asaad Zuby. The President of the Conference and the Local Organizing Committee was Dr. Adnan Farah, the Chair of the Scientific Program Committee was Dr. Mohammad Rimawi, and the Chair of the Regional Advisory Committee was Dr. Marwan Dwairy. The Conference succeeded in attracting participants from 28 countries, including 15 from the Middle East and North Africa region. The Scientific Program explored ways and means to promote the role of psychology in meeting life challenges at regional and international levels. The Conference concluded with the signing of a formal Declaration which called upon governments, academic and professional institutions and organizations, non-governmental organization and other civil society groups, and the United Nations, to work together and to make every possible effort individually and collectively to achieve these goals.

  16. 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.

  17. 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

  18. 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.

  19. Psychological Treatment

    Science.gov (United States)

    ... cognitive-behavioral therapy ), relaxation therapy , hypnotherapy , and biofeedback therapy . Psychological treatments can also be combined. Review of well- ... Antidepressant Medications Newer IBS Medications Probiotics and Antibiotics ... Cognitive Behavioral Therapy Relaxation Techniques for IBS Take Part in Online ...

  20. Description of Work for Borehole Sampling at the 116-DR-1and 116-DR-2 Trenches

    International Nuclear Information System (INIS)

    Bergstrom, K. A.

    1999-01-01

    This description of work (DOW) details the sampling and analysis activities for characterizing the deep zone soils below the 116-DR-1and 116-DR-2 trenches, which are located in the 100-DR- 1 Operable Unit (OU), and will serve as a guide for the personnel performing the work. The ''deep zone'' refers to the portion of the vadose zone between the bottom of the waste site and the water table. The scope of work includes drilling a borehole (B8786), sampling vadose zone and upper saturated zone soils at ∼ 1-m intervals, collecting a water sample below the top of the water table, and analyzing the samples for all contaminants of concern (COCs). Specific procedures for defined tasks are covered under the Bechtel Hanford, Inc. (BHI)manual, BHI-EE-01, Environmental Investigations Procedures

  1. [Psychological harassment].

    Science.gov (United States)

    Puech, Paloma; Pitcho, Benjamin

    2013-04-01

    Two types of harassment are distinguished: sexual and psychological. In the private sector, according to French labour laws and the penal code, psychological harassment is actionable. It is up to the employer to prove the absence of harassment. The sanctions incurred can be up to 5 years imprisonment and a 150,000 euro fine and various measures of compensation for damages can be envisaged.

  2. Dr. David Syz, State Secretary for Economic Affairs, Switzerland

    CERN Multimedia

    Maximilien Brice

    2003-01-01

    Dr. David Syz, State Secretary for Economic Affairs, Switzerland, toured the assembly hall of the ATLAS experiment on a recent visit to CERN.Photos 01, 02: Dr. Peter Jenni, spokesperson for the ATLAS experiment (second from left), explains to Dr. David Syz (fourth from left) and accompanying visitors the process of integration of a 26-metre-long coil of the barrel toroid magnet system into its coil casing.Photo 03: Dr. Peter Jenni (extreme right) with Dr. David Syz (front row, fourth from right) behind a stack of 26-metre-long 'racetrack' coils awaiting integration into their coil casings.

  3. Prof. DR. F. C. Eloff - An appreciation

    Directory of Open Access Journals (Sweden)

    G de Graaff

    1984-12-01

    Full Text Available I have been requested to write an appreciation of the man to whom these proceedings of a symposium on the Kalahari Ecosystem are dedicated @ Prof. Dr. F. C. Eloff, or Fritz as he is popularly referred to. I undertook the task with some trepidation and the only claim to the honour to write this article may be the fact that I have known Professor Eloff since 1949 when I was a green-shanked first year veterinary student at the University of Pretoria where he lectured in zoology to the new students.

  4. HLA-DR typing by radioimmunoassay

    International Nuclear Information System (INIS)

    Tosi, R.; Tanigaki, N.; Centis, D.; Rossi, P.L.; Alfano, G.; Ferrara, G.B.; Pressman, D.

    1980-01-01

    A radioimmunoassay procedure is described by which peripheral blood lymphocytes can be typed for HLA-DR specificities. The major advantages of this method are the following: simple and reproducible procedure, no need for B lymphocyte separation, no need for optimal viability, and no need for preabsorption of antisera with platelets. This method will find an application in the genetic and biochemical analysis of the HLA complex, and in the clinical tests of Ia antigens for diagnostic or prognostic purposes and in retrospective transplant studies

  5. Whither Psychology.

    Science.gov (United States)

    Halpern, Diane F

    2017-07-01

    Contemporary psychology is experiencing tremendous growth in neuroscience, and there is every indication that it will continue to gain in popularity notwithstanding the scarcity of academic positions for newly minted Ph.Ds. Despite the general perception that brain correlates "explain" or "cause" the mind and behavior, these correlates have not yet proven useful in understanding psychological processes, although they offer the possibility of early identification of some disorders. Other recent developments in psychology include increased emphasis on applications and more global representation among researchers and participants. In thinking about the way we want psychology to evolve, psychologists need to pay more than lip service to the idea that complex questions in psychology require multiple levels of analysis with contributions from biological (brain, hormones, and genetics), individual differences and social and cultural perspectives. Early career psychologists who can attain a breadth of knowledge will be well-positioned for a team approach to psychological inquiry. Finally, I offer the belief that an emphasis on enhancing critical thinking skills at all levels of education offers the best hope for the future.

  6. 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...

  7. 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.

  8. 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.

  9. 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.

  10. 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…

  11. 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…

  12. 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.

  13. 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…

  14. 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.

  15. 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.

  16. 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-...

  17. 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

  18. 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.)

  19. HLA-DR expression and disease activity in ulcerative colitis

    DEFF Research Database (Denmark)

    Poulsen, L O; Elling, P; Sørensen, Flemming Brandt

    1986-01-01

    In 12 patients with active ulcerative colitis (UC) the rectal epithelial cells were analyzed for HLA-DR antigens by an immunohistochemical technique. The clinical, rectoscopic, and histologic stages were also determined. The investigations were carried out at the beginning of the study and 2 weeks...... and 3 months later. The rectal epithelial cells were HLA-DR-positive in all patients at the first two examinations. After 3 months five patients had changed to an HLA-DR-negative stage, whereas the other seven patients remained HLA-DR-positive. Closer analyses showed that expression/nonexpression of HLA-DR...... antigens on rectal epithelial cells of patients with UC could not be predicted from the clinical, rectoscopic, or histologic findings. HLA-DR expression is normally restricted to immunocompetent cells. The presence of HLA-DR antigens on epithelial cells may be a consequence of immunological reactions...

  20. 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.

  1. 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...

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. Political psychology.

    Science.gov (United States)

    Stone, Susanna; Johnson, Kate M; Beall, Erica; Meindl, Peter; Smith, Benjamin; Graham, Jesse

    2014-07-01

    Political psychology is a dynamic field of research that offers a unique blend of approaches and methods in the social and cognitive sciences. Political psychologists explore the interactions between macrolevel political structures and microlevel factors such as decision-making processes, motivations, and perceptions. In this article, we provide a broad overview of the field, beginning with a brief history of political psychology research and a summary of the primary methodological approaches in the field. We then give a more detailed account of research on ideology and social justice, two topics experiencing a resurgence of interest in current political psychology. Finally, we cover research on political persuasion and voting behavior. By summarizing these major areas of political psychology research, we hope to highlight the wide variety of theoretical and methodological approaches of cognitive scientists working at the intersection of psychology and political science. WIREs Cogn Sci 2014, 5:373-385. doi: 10.1002/wcs.1293 For further resources related to this article, please visit the WIREs website. The authors have declared no conflicts of interest for this article. © 2014 John Wiley & Sons, Ltd.

  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. Enrico Fermi Awards Ceremony for Dr. Mildred S. Dresselhaus and Dr. Burton Richter, May 2012 (Presentations, including remarks by Energy Secretary, Dr. Steven Chu)

    International Nuclear Information System (INIS)

    Chu, Steven

    2012-01-01

    The Fermi Award is a Presidential award and is one of the oldest and most prestigious science and technology honors bestowed by the U.S. Government. On May 7, 2012 it was conferred upon two exceptional scientists: Dr. Mildred Dresselhaus, 'for her scientific leadership, her major contributions to science and energy policy, her selfless work in science education and the advancement of diversity in the scientific workplace, and her highly original and impactful research,' and Dr. Burton Richter, 'for the breadth of his influence in the multiple disciplines of accelerator physics and particle physics, his profound scientific discoveries, his visionary leadership as SLAC Director, his leadership of science, and his notable contributions in energy and public policy.' Dr. John Holder, Director of the White House Office of Science and Technology Policy, opened the ceremony, and Dr. Bill Brinkman, Director of DOE's Office of Science introduced the main speaker, Dr. Steven Chu, U.S. Energy Secretary.

  10. 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.

  11. 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...

  12. 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.

  13. 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...

  14. 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...

  15. 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...

  16. 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.

  17. 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)

  18. Decommissioning of DR 2. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Strufe, N.

    2009-02-15

    This report describes the work of dismantling and demolishing reactor DR 2, the waste volumes generated, the health physical conditions and the clearance procedures used for removed elements and waste. Since the ultimate goal for the decommissioning project was not clearance of the building, but downgrading the radiological classification of the building with a view to converting it to further nuclear use, this report documents how the lower classification was achieved and the known occurrence of remaining activity. The report emphasises some of the deliberations made and describes the lessons learned through this decommissioning project. The report also intends to contribute towards the technical basis and experience basis for further decommissioning of the nuclear facilities in Denmark. (au)

  19. Interview with Professor Dr. Daniel Spreng

    International Nuclear Information System (INIS)

    Nagel, C.; Kilchmann, A.

    2004-01-01

    This interview with Professor Dr. Daniel Spreng of the Center for Energy Policy and Economics (CEPE) in Zuerich, Switzerland, deals with questions concerning research in the area of energy economics. In particular, the situation in Switzerland, where mains-connected sources of energy such as electricity and gas play an important role in energy supply, is looked at in the light of market liberalisation. Various approaches to the liberalisation of gas and electricity systems are discussed and the costs of liberalised supply systems are compared with those of the present monopolistic situation. Also, energy reserves and the use of the gas distribution system in a future hydrogen-based energy supply scenario are looked at. Projects currently being worked on at the CEPE are reviewed

  20. Gaia DR2 documentation Chapter 3: Astrometry

    Science.gov (United States)

    Hobbs, D.; Lindegren, L.; Bastian, U.; Klioner, S.; Butkevich, A.; Stephenson, C.; Hernandez, J.; Lammers, U.; Bombrun, A.; Mignard, F.; Altmann, M.; Davidson, M.; de Bruijne, J. H. J.; Fernández-Hernández, J.; Siddiqui, H.; Utrilla Molina, E.

    2018-04-01

    This chapter of the Gaia DR2 documentation describes the models and processing steps used for the astrometric core solution, namely, the Astrometric Global Iterative Solution (AGIS). The inputs to this solution rely heavily on the basic observables (or astrometric elementaries) which have been pre-processed and discussed in Chapter 2, the results of which were published in Fabricius et al. (2016). The models consist of reference systems and time scales; assumed linear stellar motion and relativistic light deflection; in addition to fundamental constants and the transformation of coordinate systems. Higher level inputs such as: planetary and solar system ephemeris; Gaia tracking and orbit information; initial quasar catalogues and BAM data are all needed for the processing described here. The astrometric calibration models are outlined followed by the details processing steps which give AGIS its name. We also present a basic quality assessment and validation of the scientific results (for details, see Lindegren et al. 2018).

  1. The cold neutron source in DR 3

    International Nuclear Information System (INIS)

    Jensen, K.; Leth, j.A.

    1980-09-01

    A description of the cold neutron source in DR 3 is given. The moderator of the cold neutron source is supercritical hydrogen at about 30degK and 15 bar abs. The necessary cooling capacity is supplied by two Philips Stirling B20 cryogenerators. The hydrogen is circulated between the cryogenerators and the in-pile moderator chamber by small fans. The safety of the facility is based on the use of triple containment preventing contact between hydrogen and air. The triple containment is achieved by enclosing the high vacuum system, surrounging the hydrogen system, in a helium blanket. The achieved spectrum of the thermal neutron flux and the gain factor are given as well as the experience from more than 5 years of operation. Finally some work on extension of the facility to operate two cold sources is reported. (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. 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

  9. Dr. Hans Chang, Director, Physics Research Committee, Stichting voor Fundamenteel Onderzoek der Materie (FOM), Dr. Joris Van Enst, Head of Science Policy Division, Ministry of Education, Culture and S cience, Dr. Jan Bezemer, NL Delegate CERN, Netherlands

    CERN Multimedia

    Patrice Loiez

    1999-01-01

    Dr. Hans Chang, Director, Physics Research Committee, Stichting voor Fundamenteel Onderzoek der Materie (FOM), Dr. Joris Van Enst, Head of Science Policy Division, Ministry of Education, Culture and S cience, Dr. Jan Bezemer, NL Delegate CERN, Netherlands

  10. 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.

  11. Psychological IVF

    DEFF Research Database (Denmark)

    Adrian, Stine Willum

    2015-01-01

    ’. This theoretical work has three aims. First, it seeks to illustrate how the story of psychological IVF offers a rich range of materializations of emotions. Secondly, this work proposes a feminist materialist conceptualization of emotions that is both non-representational and posthuman. This conceptualization draws...

  12. Space psychology

    Science.gov (United States)

    Parin, V. V.; Gorbov, F. D.; Kosmolinskiy, F. P.

    1974-01-01

    Psychological selection of astronauts considers mental responses and adaptation to the following space flight stress factors: (1) confinement in a small space; (2) changes in three dimensional orientation; (3) effects of altered gravity and weightlessness; (4) decrease in afferent nerve pulses; (5) a sensation of novelty and danger; and (6) a sense of separation from earth.

  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. Goldie Brangman Remembers the Operation to Save Dr King.

    Science.gov (United States)

    Koch, Evan; Brangman, Goldie

    2015-12-01

    In September 1958 the Rev Dr Martin Luther King Jr was stabbed and nearly assassinated. Surgeons at Harlem Hospital in New York City removed a 17.8-cm (7-in)-long letter opener from Dr King's chest. Certified Registered Nurse Anesthetist Goldie Brangman remembers this event because she participated in Dr King's anesthetic. This article correlates Brangman's memories with published accounts of the event. It also places the event within the context of the modern civil rights movement that Dr King led.

  16. 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.

  17. 95 GHz methanol masers near DR 21 and DR 21(OH)

    International Nuclear Information System (INIS)

    Plambeck, R.L.; Menten, K.M.

    1990-01-01

    The BIMA array is used to map the 95-GHz 8(0) to 7 1A(+) transition of methanol and the 98-GHz J = 2-1 transition of CS toward the DR 21(OH) and DR 21 star-forming regions. Several strong methanol masers were found. The positions of the two brightest masers were measured with an accuracy of about + or - 0.3 arcsec. Toward DR 21(OH), the positions, velocities, and line shapes of the 95 GHz masers are in excellent agreement with those of the 84-GHz 5(-1) to 4 () methanol masers previously mapped by Batrla and Menten (1988), demonstrating that maser emission in both transitions originates from the same clumps of gas. The methanol masers are offset from CS emission peaks and from other known infrared and maser sources; they may possibly be clustered along the interface between outflows, traced by shock-excited H2 emission, and dense ambient gas, traced by CS emission. 25 refs

  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. 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.

  3. Dr. Hall and the work cure.

    Science.gov (United States)

    Reed, Kathlyn L

    2005-01-01

    Herbert James Hall, MD (1870-1923), was a pioneer in the systematic and organized study of occupation as therapy for persons with nervous and mental disorders that he called the "work cure." He began his work in 1904 during the early years of the Arts and Crafts Movement in the United States. His primary interest was the disorder neurasthenia, a condition with many symptoms including chronic fatigue, stress, and inability to work or perform everyday tasks. The prevailing treatment of the day was absolute bed rest known as the "rest cure." Hall believed that neurasthenia was not caused by overwork but by faulty living habits that could be corrected through an ordered life schedule and selected occupations. He identified several principles of therapy that are still used today including graded activity and energy conservation. Dr. Adolph Meyer credits Hall for organizing the ideas on the therapeutic use of occupation (Meyer, 1922). Hall also provided the name American Occupational Therapy Association for the professional organization and served as the fourth president. For his many contributions to the profession Hall deserves to be recognized as a major contributor to the development and organization of occupational therapy.

  4. Dr. Rudolph Binion: professor, mentor, psychohistorian.

    Science.gov (United States)

    Szaluta, Jacques

    2015-01-01

    As the title of my paper indicates, Dr. Rudolph Binion was my professor, mentor, and a leading psychohistorian. My paper in memoriam to Rudolph Binion is intended as both a retrospective and an introspective account of my relationship with him, as he had a pivotal influence on me when he was my professor at Columbia University. His help and influence continued after I left graduate school. In my paper I also deal with the enormous stresses of navigating through graduate school, for those students whose goal was to earn the Ph.D. degree. Some examinations were dreaded, For Example The "Examination in Subjects," popularly called the "Oral Exam." The "incubation" period was long indeed, frequently averaging nearly ten years, and it was an ordeal, as the rate of attrition was very high. There is then also the question of "ego strength" and that of "transference" toward the professor. Graduate school is indeed a long and strenuous challenge. I took a seminar in modern French history, a requirement for the Master's degree with Professor Binion, which was consequential for me, as he taught me to be objective in writing history. Professor Binion was a demanding and outstanding teacher.

  5. SDSS DR7 WHITE DWARF CATALOG

    Energy Technology Data Exchange (ETDEWEB)

    Kleinman, S. J.; Nitta, A. [Gemini Observatory, 670 North A' ohoku Place, Hilo, HI 96720 (United States); Kepler, S. O.; Pelisoli, Ingrid; Pecanha, Viviane; Costa, J. E. S. [Instituto de Fisica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Koester, D. [Institut fuer Theoretische Physik und Astrophysik, Universitaet Kiel, D-24098 Kiel (Germany); Krzesinski, J. [Mt. Suhora Observatory, Pedagogical University of Cracow, ul. Podchorazych 2, 30-084 Cracow (Poland); Dufour, P.; Lachapelle, F.-R.; Bergeron, P. [Departement de Physique, Universite de Montreal, C. P. 6128, Succ. Centre-Ville, Montreal, Quebec H3C 3J7 (Canada); Yip, Ching-Wa [Department of Physics and Astronomy, The Johns Hopkins University, 3701 San Martin Drive, Baltimore, MD 21218 (United States); Harris, Hugh C. [United States Naval Observatory, Flagstaff Station, 10391 West Naval Observatory Road, Flagstaff, AZ 86001-8521 (United States); Eisenstein, Daniel J. [Harvard Smithsonian Center for Astrophysics, 60 Garden Street, MS 20, Cambridge, MA 02138 (United States); Althaus, L.; Corsico, A., E-mail: hch@nofs.navy.mil [Facultad de Ciencias Astronomicas y Geofisicas, Paseo del Bosque S/N, (1900) La Plata (Argentina)

    2013-01-15

    We present a new catalog of spectroscopically confirmed white dwarf stars from the Sloan Digital Sky Survey (SDSS) Data Release 7 spectroscopic catalog. We find 20,407 white dwarf spectra, representing 19,712 stars, and provide atmospheric model fits to 14,120 DA and 1011 DB white dwarf spectra from 12,843 and 923 stars, respectively. These numbers represent more than a factor of two increase in the total number of white dwarf stars from the previous SDSS white dwarf catalogs based on DR4 data. Our distribution of subtypes varies from previous catalogs due to our more conservative, manual classifications of each star in our catalog, supplementing our automatic fits. In particular, we find a large number of magnetic white dwarf stars whose small Zeeman splittings mimic increased Stark broadening that would otherwise result in an overestimated log g if fit as a non-magnetic white dwarf. We calculate mean DA and DB masses for our clean, non-magnetic sample and find the DB mean mass is statistically larger than that for the DAs.

  6. A Tribute to Prof Dr Da Ruan

    CERN Document Server

    Kerre, Etienne

    2013-01-01

    This volume is a tribute to Professor Dr Da Ruan, who passed away suddenly on July 31, 2011, aged 50. The flood of emails that spread throughout the fuzzy logic research community with the tragic news was testimony to the respect and liking felt for this remarkable man. Da was a hardworking , highly productive scientist who, during his short life, published 35 books and more than 250 research papers in highly ranked journals and conference proceedings. He established two successful conferences, FLINS and ISKE, as well as the international journal, JCIS. This book is a collection of contributions from 88 of Da's academic friends from 47 institutes, presented in 60 chapters and over 70 pictures. A Foreword by Lotfi Zadeh begins Da's story. Section 1 provides an overview of Da's funeral on August 6, 2011. Part II outlines Da’s scientific life, his education, scientific career, publications and keynote talks. Part III presents testimonials by Da's colleagues of academic activities, including guest professorship...

  7. 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.

  8. 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.

  9. 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).

  10. 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.

  11. Dr. Irene Sänger-Bredt, a life for astronautics

    Science.gov (United States)

    Zaganescu, Nicolae-Florin

    2004-12-01

    Irene Bredt (b.1911 at Bonn) obtained her Doctorate in Physics in 1937; in the same year she became a scientific researcher at the German Research Center for Aviation at Trauen, led by Prof. Dr. Eugen Sänger. Soon, the young but efficient Dr. Irene Bredt became the first assistant of Dr. Sänger, who married her (1951). During 1973-1978, Dr. Bredt was in correspondence with Prof. Dr. Nikolae-Florin Zaganescu and helped him to familiarize the Romanian readers with Prof. Sänger's life and achievements. As for Dr. Bredt's life, she specified three main periods of her activity: 1937-1942, when she was researcher in charge of thermodynamic problems of liquid-fuelled rocket engines at Trauen 1942-1945, when she was Senior Researcher in charge of Ramjet in flight performances at Ainring, and also coauthored the Top Secret Technical report entitled 'A Rocket Engine for a Long-Range Bomber', which was finished in 1941 but edited only in 1944 the post world war II period, when she was Scientific Advisor or Director at various civil and military research institutes, universities, etc. Dr. Irene Sänger-Bredt helped her husband to develop many scientific theories like Ramjet thermodynamic theory, and photon rocket theory and also in establishing IAF and IAA. In 1970, Dr. Irene Sänger-Bredt was honored with 'Hermann Oberth Gold Medal' for her impressive scientific activity.

  12. Interview with Smithsonian NASM Spacesuit Curator Dr. Cathleen Lewis

    Science.gov (United States)

    Lewis, Cathleen; Wright, Rebecca

    2012-01-01

    Dr. Cathleen Lewis was interviewed by Rebecca Wright during the presentation of an "Interview with Smithsonian NASM Spacesuit Curator Dr. Cathleen Lewis" on May 14, 2012. Topics included the care, size, and history of the spacesuit collection at the Smithsonian and the recent move to the state-of-the-art permanent storage facility at the Udvar-Hazy facility in Virginia.

  13. Celebrating the Life and Legacy of Dr. John Hope Franklin

    Science.gov (United States)

    Harris, Robert L., Jr.; Levering-Lewis, David; French, John D.; Wharton, Clifton R., Jr.

    2009-01-01

    Dr. John Hope Franklin chronicled the experiences of African-Americans like no one before him, forcing America to recognize Black history as American history. His contributions were innumerable and his impact was abiding. In celebration of his life and legacy, the authors profile the celebrated scholar and activist, Dr. John Hope Franklin.

  14. Dr. Albert Carr--Science Educator 1930-2000

    Science.gov (United States)

    Lopez, Leslie

    2013-01-01

    The very first issue of "Educational Perspectives" was published in October of 1962. Dr. Albert Carr wrote one of the inaugural essays on the topic of current developments in science education, and he went on to write several other articles for the journal. This article shares why Dr. Albert Carr's colleagues remember him for his…

  15. Profile Interview: Dr. Patrick Dongosolo Kamalo – Consultant ...

    African Journals Online (AJOL)

    Dr. Yohane Gadama (YG), an MMJ intern, interviews Dr. Patrick Dongosolo Kamalo (PDK) on his work as Malawi's only local practicing neurosurgeon, the launch of Blantyre Institute of Neurological Sciences (BINS) and the beginning of Neurosurgery training in Malawi ...

  16. Dr. Praveen Chaudhari named director of Brookhaven National Laboratory

    CERN Multimedia

    2003-01-01

    "Brookhaven Science Associates announced today the selection of Dr. Praveen Chaudhari as Director of the U.S. Department of Energy's Brookhaven National Laboratory. Dr. Chaudhari, who will begin his new duties on April 1, joins Brookhaven Lab after 36 years of distinguished service at IBM as a scientist and senior manager of research" (1 page).

  17. Association of differentiated thyroid carcinoma with HLA-DR7

    International Nuclear Information System (INIS)

    Sridama, V.; Hara, Y.; Fauchet, R.; DeGroot, L.J.

    1985-01-01

    Seventy-four American white thyroid cancer patients were typed for HLA-A, B, and DR antigens. A significant increase in HLA-DR7 was found in the nonradiation-associated thyroid cancer patients (42.5%, 20/47 cases), compared to 22.8% of 979 normal controls. The association is stronger in the follicular and mixed papillary-follicular subgroup (52.0%, 13/25 cases, P corrected less than 0.01). The occurrence of various malignancies in family members was found in 57.9% of HLA-DR7 positive patients, versus 20% of HLA-DR7 negative patients, in a retrospective record review. Although the frequency of HLA-DR7 was not increased in the radiation-associated thyroid cancer patients (22.2%, 6/27 cases), the interval from the irradiation date to the onset date of thyroid cancer was shorter in HLA-DR7 positive cases (17.3 +/- 6.2 years) than in HLA-DR7 negative patients (29.4 +/- 11.5 years). This data suggest that HLA-DR7 is associated with and may influence development of thyroid cancer

  18. 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.

  19. Dr. Martin Luther King, Jr. as Spiritual Leader

    Directory of Open Access Journals (Sweden)

    Andrea Pierce

    2013-09-01

    Full Text Available The purpose of this paper is to explore Dr. Martin Luther King Jr.’s spiritual leadership through his “I Have a Dream” speech. The paper explores the three characteristics of spiritual leadership as posed by Fry’s (2003 spiritual leadership theory: vision, hope/faith and altruistic love. The research draws upon these characteristics through qualitative content analysis of Dr. Martin Luther King Jr.’s “I Have a Dream” speech to illustrate Dr. King’s leadership as that of a spiritual leader. The research advances the spiritual leadership theory by establishing Dr. Martin Luther King Jr. as a spiritual leader. Through the illustration of Dr. King’s spiritual leadership, the characteristics of a spiritual leader are given tangible understanding.

  20. 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.

  1. Comparaison du Srōš Drōn avec le Drōn Yašt

    OpenAIRE

    Redard, Céline

    2015-01-01

    This paper draws a parallel between two texts having the same textual base: The Srōš Drōn, derived from the Long Liturgy and the Drōn Yašt, belonging to the short liturgies. The goal is to establish the similarities and the discrepancies between these two texts. Peer reviewed

  2. Psychology Faculty Perceptions of Abnormal Psychology Textbooks

    Science.gov (United States)

    Rapport, Zachary

    2011-01-01

    The problem. The purpose of the current study was to investigate the perceptions and opinions of psychology professors regarding the accuracy and inclusiveness of abnormal psychology textbooks. It sought answers from psychology professors to the following questions: (1) What are the expectations of the psychology faculty at a private university of…

  3. Psychology of religion: perspectives from cultural psychology

    NARCIS (Netherlands)

    Belzen, J.A.

    2010-01-01

    After a brief introduction, this paper tries to establish what type of psychology the psychology of religion is. Having introduced cultural psychology in general, some theories applicable in research on religion are presented, and some examples of cultural psychological research of religious

  4. Profil épidémiologique des hémoglobinopathies: étude transversale descriptive autour du cas index

    Science.gov (United States)

    Dahmani, Fatima; Benkirane, Souad; Kouzih, Jaafar; Woumki, Aziz; Mamad, Hassan; Masrar, Azlarab

    2017-01-01

    Les hémoglobinopathies sont des affections constitutionnelles conséquentes à des anomalies des hémoglobines. Elles sont souvent graves dans leurs formes majeures, leur prise en charge est lourde avec un grand impact psycho-social sur les patients et leur famille. Classées parmi les maladies rares, elles sont encore insuffisamment connues des professionnels de santé. Cette méconnaissance est à l'origine d'une errance diagnostique, d'un retard dans leur prise en charge et par conséquent une morbidité et une mortalité élevée chez ces patients. L'Organisation Mondiale de la Santé (OMS) a publié en 2008 des données concernant l'épidémiologie des hémoglobinopathies: plus de 330000 cas naissent chaque année avec une hémoglobinopathie (83% des cas de drépanocytose, 17% des cas de thalassémie). Les troubles de l'hémoglobine sont responsables d'environ 3,4% des décès chez les moins de 5 ans. A l'échelle mondiale, 7% environ des femmes enceintes seraient porteuses d'une forme de la thalassémie et 1% des couples sont à risque. Toutefois, elles sont relativement fréquentes dans certaines régions du globe où les mariages consanguins sont communs. Afin de décrire les caractéristiques épidémiologiques des familles à risque d'hémoglobinopathies (étude autour du cas) dont les cas index sont suivis au service de pédiatrie à l'Hôpital Provincial El Idrisi de Kenitra au Maroc, une étude transversale descriptive a été réalisée durant deux enquêtes la première en mai 2015 et la deuxième en juin de la même année lors des journées de vaccination des cas index contre le pneumocoque. Après avoir recueilli les données épidémiologiques de nos patients, nous avons réalisé une étude biologique comportant: l'hémogramme avec étude morphologique des globules rouges en coloration MGG et numération automatique des réticulocytes; les électrophorèses de l'hémoglobine à pH alcalin (8.8) et secondairement à pH acide (5.4) sur gel d

  5. 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.

  6. 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.

  7. Prava trećih država u gospodarskom pojasu obalne države

    Directory of Open Access Journals (Sweden)

    Marina Vokić Žužul

    2003-12-01

    Full Text Available Predmet ovoga rada je analiza prava koja u gospodarskom pojasu obalne države mogu ostvarivati sve obalne i neobalne države. uz detaljan prikaz pravnog uređenja materije u odredbama Konvencije o pravu mora iz 1982., razmatraju se i vladajuća gledišta međunarodnopravne doktrine te rješenja u zakonodavstvima pojedinih zemalja. Posebna pozornost je posvećena ostvarivanju tuh prava u potencijalnom hrvatskom gospodarskom pojasu, prvenstveno mogućim zahtjevima od strane susjednih neobalnih država i država u nepovoljnom geografskom položaju. Sva pitanja razmatrana u ovom radu upućuju na zaključak da ispunjavanje dužnosti prema drugim državama u budućem gospodarskom pojasu RH ne bi trebalo imati utjecaja na donošenje odluke o njegovom proglašenju.

  8. 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.

  9. Impact of Disordered Eating and Psychological Functioning on Overweight Adolescents Participating in a Placebo-Controlled Medication and Behavioral Weight Loss Trial

    Science.gov (United States)

    2009-11-23

    episodes in bulimia nervosa: possible influences of the serotonin system. Psychological Medicine, 35(11), 1553-1562. Steinberg, E., Tanofsky-Kraff, M...HEALTH Ph.D. Degrees Interdisciplinary -Emerging Infectious Diseases -Molecular & Cell Biology -Neuroscience Departmental -Clinical Psychology ...Environmental Health Sciences -Medical Psychology -Medical Zoology Physician Scientist (MDlPh.D.) Doctor of Public Health (Dr.P.H.) Master of

  10. Dr. Steve Thompson, Chief Executive, The Royal Society of New Zealand

    CERN Multimedia

    Maximilien Brice

    2002-01-01

    L. to r.: Dr Austin Ball, Deputy Technical Coordinator, CMS experiment; Dr Roland Horisberger, Paul Scherrer Institute and CERN, CMS experiment; Dr Steve Thompson, Chief Executive, The Royal Society of New Zealand; Dr Michel Della Negra, Spokesman, CMS experiment and Dr Alick Macpherson, Paul Scherrer Institute and CERN, CMS experiment, in the CMS Silicon Tracker assembly hall.

  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. [Dr. Luis Cifuentes Delatte. Memories and teaching].

    Science.gov (United States)

    Pérez Albacete, Mariano

    2008-12-01

    With the celebration of the centenary of the birth of Dr. Luis Cifuentes Delatte, due to his great scientific personality, we want to emphasize two features that, taken from his works and memories, we consider have not been emphasized enough: his role as historian of urology, both for the histories he narrated of his life experiences and the historical exposition of several pathologies, and also his teaching as professor of several generations of urologists, with the objective of trying to get to know his great human quality as he demonstrated over his life and showed in his writings. We review his books and works, lectures and published papers, in addition the news about his person we have collected from the media, and after analysis, mainly of his memories, we extract data reflecting his personality, and they way he thought and behaved. Since he was young he went with his father to the international urology meetings where he met a great number of personalities in the World of Urology; he extended his training with them, and later on they got to have a great relationship. He travelled around Europe and United States before and after Second World War, respectively, with stays in the most prestigious centers, which he described meticulously. He also reported his activity during the first two years he directed the Department of Urology at the Hospital La Princesa in Madrid and cited the series of collaborators he had. In his research works he made an ample description of historical development as introduction to the various pathologies he analyzed in depth. The reading of the narration of his trips, that he did in the convulse International time he lived, offers details which enable us to know firsthand the situation of urology and the human side of the actors he had relation with, and the social life they had, in addition to data about their families and daily life. As a researcher in transcendental chapters in urological pathology we emphasize his historical

  13. 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.

  14. 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

  15. 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

  16. 1016-IJBCS-Article-Dr Koffi Mathias Yao

    African Journals Online (AJOL)

    DR GATSING

    d'alcool, de sexe masculin dont 50 sujets témoins et 346 sujets tests répartis en deux groupes : 173 ont ... deux groupes de sujets tests ont des performances semblables comme ce fut le cas ..... Harris DS, Everhart ET, Mendelson J, Jones.

  17. Psychological barriers

    DEFF Research Database (Denmark)

    Skinner, T. C.

    2004-01-01

    Type 2 diabetes treatment outcomes ultimately depend on patients and their ability to make long-term behavioural changes that support good self-care and metabolic control. Patients' perceptions about diabetes and diabetes-related complications can have a strong influence on their emotional well...... of lifestyle changes and pharmacological therapy in preventing future complications. Negative emotions and preconceptions about treatment can also discourage adherence to treatment plans. 'Psychological Insulin resistance' caused by fear and concerns about insulin and daily insulin injections can discourage...... many patients from starting insulin therapy, even if oral agents have failed. Depression, stress and anxiety represent further obstacles to optimum self-care and the attainment of glucose goals. Healthcare professionals should endeavour to understand and accommodate these issues when setting personal...

  18. 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.

  19. Grantee Spotlight: Dr. Kolawole Okuyemi - Improving Cervical Cancer Screening Attitudes

    Science.gov (United States)

    Dr. Kolawole Okuyumi is studying cervical cancer screening attitudes and behaviors of African immigrants and refugees (Ethiopians, Nigerians, and Somalis) in Minnesota, and introducing “cancer” and “cervix” to their everyday vocabulary.

  20. 105-DR large sodium fire facility closure Plan. Revision 2

    International Nuclear Information System (INIS)

    Ruck, F.A. III.

    1995-03-01

    The 105-DR Large Sodium Fire Facility (LSFF), which was operated 1972-1986, was a research laboratory that occupied the former ventilation supply room on the SW side of the 105-DR Reactor Facility. (The 105-DR defense reactor was shut down in 1964.) LSFF was used to investigate fire and safety aspects of large sodium or other metal alkali fires in the LMFBR facilities; it was also used to store and treat alkali metal waste. This closure plan presents a description of the unit, the history of the waste managed, and the procedures that will be followed to close the LSFF as an Alkali Metal Treatment Facility. No future use of LSFF is expected. It is located within the 100-DR-2 (source) and 100-HR-3 (groundwater) operable units, which will be addressed through the RCRA facility investigation/corrective measures study process

  1. Glaucoma: Eye-to-Eye with Dr. Rachel Bishop

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Glaucoma Eye-to-Eye with Dr. Rachel Bishop Past ... nerves are pale and cupped—signs of advanced glaucoma. Yet the patient wasn't aware of any ...

  2. Decommissioning of DR 2. Experiences learnt from the completion

    International Nuclear Information System (INIS)

    Strufe, N.

    2009-10-01

    The report describes experiences gathered from the decommissioning of DR 2. The experiences encompasses planning and management of the project, methods of accomplishment, and various materials categories. Additionally, the report describes the experience with specific tools used in the project

  3. Dr. Ted Trimble: Why I Do Cancer Research

    Science.gov (United States)

    In a video, Dr. Ted Trimble talks about the importance of cancer research. World Cancer Research Day commemorates the important role research and cancer researchers play in reducing the global burden of cancer.

  4. Grading diabetic retinopathy (DR using the Scottish grading protocol

    Directory of Open Access Journals (Sweden)

    Sonia Zachariah

    2016-04-01

    Full Text Available Although traditionally the features of DR have been identified through direct ophthalmoscopy or slit lamp biomicroscopy, digital photography is more sensitive than direct ophthalmoscopy and is comparable to slit lamp examination by a trained observer.

  5. Dr. Omalu Talks Childhood, Concussions, and CTE | Poster

    Science.gov (United States)

    Dr. Bennet Omalu, the famed forensic pathologist who discovered Chronic Traumatic Encephalopathy (CTE), recently spoke at NCI at Frederick about his upbringing as well as the trials he faced while working to educate the NFL about CTE.

  6. Dr Abraham Pais, 82, physicist and science historian dies

    CERN Document Server

    Glanz, J

    2000-01-01

    Obituary of Dr. Pais who died of heart failure in Copenhagen. He helped build the conceptual foundations of particle physics and then became a science historian, writing a critically acclaimed biography of Einstein (1 pg).

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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...

  13. 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.

  14. 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

  15. Portrait of Dr. Von Braun with Walt Disney, 1954.

    Science.gov (United States)

    1954-01-01

    Marshall Center Director Dr. Wernher Von Braun is pictured with Walt Disney during a visit to the Marshall Space Flight Center in 1954. In the 1950s, Dr. Von Braun while working in California on the Saturn project, also worked with Disney studios as a technical director in making three films about Space Exploration for television. Disney's tour of Marshall in 1965 was Von Braun's hope for a renewed public interest in the future of the Space Program at NASA.

  16. The research contributions of Dr. Paul Van Deusen

    Science.gov (United States)

    Thomas B. Lynch; Francis A. Roesch; John Paul McTague; Jeffrey H. Gove; Gregory A. Reams; Aaron R. Weiskittel

    2015-01-01

    Dr. Paul Van Deusen’s recent passing concluded a rich 30+-year research career dedicated to development and implementation of quantitative methods for forestry and natural resources. Since the early part of his career as a biometrician with the USDA Forest Service Southern Research Station in the 1980s-1990s and continuing with his later employment at NCASI, Dr. Van...

  17. Dr. David Syz, State Secretary for Economic Affairs, Switzerland

    CERN Multimedia

    Maximilien Brice

    2003-01-01

    Dr. David Syz, State Secretary for Economic Affairs, Switzerland is seen here (seventh from right) visiting the assembly hall for the ATLAS experiment during his recent visit to CERN. To his right is Dr. Peter Jenni (blue shirt), spokesperson for the ATLAS Collaboration. The horizontal metal cylinder behind the group is one of the eight vacuum vessels for the superconducting coils of the ATLAS barrel toroid magnet system.

  18. 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.

  19. [Sexuality education on the Internet : From Dr. Sommer to Dr. Google].

    Science.gov (United States)

    Döring, Nicola

    2017-09-01

    Female and male adolescents in Germany are increasingly using the Internet to find information about sexuality and sexual health. This review paper summarizes what we know about the status quo of online sexuality education in Germany.Based on a systematic literature review including 40 papers from international, peer-reviewed journals spanning 2010-2017, this paper first describes different aspects of the sexuality-related online search behavior of adolescents: its prevalence, predictors, topics and contexts. One main finding is the fact that adolescents use a computer or smartphone to type their sexuality-related questions into the search engine Google or the search engine of the video platform YouTube.Based on 54 online searches, this paper subsequently presents the kind of sexuality-related online content adolescents find if they ask "Dr. Google" for sexual advice; a collection of 1236 authentic sexuality-related questions of adolescents was used for this analysis. It turned out that online sexuality education offered by leading professional organizations like the BZgA ("Bundeszentrale für gesundheitliche Aufklärung") or pro familia was nearly invisible, while numerous other providers of online sex education consistently appeared in the top Google search results. Among them were the "Dr. Sommer" team of the youth magazine Bravo; online healthcare and advice portals; online forums; the online encyclopedia Wikipedia and, above all, sex education channels on YouTube. In this paper, the latter are presented in more detail for the first time.The third part of the paper addresses the quality of online sexual education over four main areas of quality evaluation. The presentation of the status quo ends with some recommendations both for future research and for sexuality education in practice.

  20. Dr. Tulp's Anatomy Lesson by Rembrandt: the third day hypothesis.

    Science.gov (United States)

    Afek, Arnon; Friedman, Tal; Kugel, Chen; Barshack, Iris; Lurie, Doron J

    2009-07-01

    An autopsy was an important event in 17th century Holland. Autopsies were held in an 'anatomy theater' and performed according to a fixed protocol that often took up to 3 days to complete. Of the five group portraits painted by Rembrandt over the course of his career, two were anatomy lessons given by Dr. Tulp and Dr. Deyman. An examination of Rembrandt's painting Dr. Tulp's Anatomy Lesson (1632) and an X-ray image of the painting, as compared to other paintings of anatomy lessons from the same period, reveal interesting differences, such as positioning, and light and shadow. Not only was the autopsy not performed according to the usual protocol, but in this painting Rembrandt created a unique dramatic scene in his effort to tell a story. We suggest that Dr. Tulp and Rembrandt "modified" the painting of Dr. Tulp's anatomy lesson to emphasize Dr. Tulp's position as the greatest anatomist of his era--"Vesalius of Amsterdam," and as a way of demonstrating God's greatness by highlighting the hand as a symbol of the most glorious of God's creations.

  1. 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

  2. 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...

  3. Psychology and Gender.

    Science.gov (United States)

    Henley, Nancy M.

    1985-01-01

    Considers recent efforts within the field of psychology to understand issues involving gender. Demonstrates patterns of development within feminist psychology and its relation to mainstream psychology. Examines status of the field, two case studies, and new research. (Author/SA)

  4. Volume celebrating the 60th birthday of Professor Dr. Franz Fie; Professor Dr. Franz Fiedler zum 60. Geburtstag

    Energy Technology Data Exchange (ETDEWEB)

    Beheng, K.D. [ed.

    1998-01-01

    This report was compiled in honor of Professor Dr. Franz Fiedler on the occasion of his 60th birthday on 7 January 1998. Its contributions deal with mesoscale modelling, the propagation of air pollutants, measurements of precipitation using radar, and prediction models. (orig./KW) [Deutsch] Dieser Bericht wurde aus Anlass des 60. Geburtstags von Herrn Prof. Dr. Franz Fiedler am 7. Januar 1998 zusammengestellt. Die Beitraege behandeln mesoskalige Modellierung, Ausbreitung von Luftschadstoffen, Niederschlagsmessung mit Radar und Vorhersagemodelle. (orig.)

  5. 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

  6. 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

  7. Psychology Ethics in Introductory Psychology Textbooks

    Science.gov (United States)

    Zucchero, Renee' A.

    2011-01-01

    Previous research revealed that introductory psychology textbooks included limited information about psychology ethics. This study reviewed 48 current introductory psychology textbooks for research and other APA ethics content. These textbooks included slightly more total ethics content and were more thorough in their review of research ethics…

  8. 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…

  9. 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.

  10. 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.

  11. 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...

  12. 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

  13. 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

  14. 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…

  15. 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.

  16. Teaching medicine with the help of "Dr. House".

    Science.gov (United States)

    Jerrentrup, Andreas; Mueller, Tobias; Glowalla, Ulrich; Herder, Meike; Henrichs, Nadine; Neubauer, Andreas; Schaefer, Juergen R

    2018-01-01

    TV series such as "House MD", "Grey´s Anatomy" or "Emergency Room" are well perceived by medical students. Seminars featuring medical TV series such as "House MD" might serve as door-opener to attract medical students to learn more about rare diseases. The TV series "House MD" is troublesome for the main character Dr. House is an excellent diagnostician but at the same time a rather misanthropic person. Therefore, lecturing medicine with the help of "House MD" requires constant evaluation. From 2008 to 2016 we are using the well-known TV series "House MD" continuously to attract medical students and teach them about rare diseases as well as diagnostic strategies. We collected from 213 students a detailed questionnaire assessing their learning experience. 76.6% of our students (n = 157) reported to watching medical dramas on a regular basis. The Dr. House seminar was compared to traditional seminars and our students reported an improved learning effect (69.9%), better concentration (89.7%), higher motivation to participate (88.7%), and more fun (86.7%) (all pHouse's behavior quite critically. Likert assessment on a 5-point scale identified strong disagreement with Dr. House´s interpersonal skills in dealing with his colleagues (median = 1) and patients (median = 1). At the same time, the students strongly agreed with his outstanding diagnostic (median = 5) and therapeutic capabilities (median = 4). Medical students visiting a Dr. House teaching seminar are highly motivated to learn more about rare diseases. They were positively influenced by TV series such as Dr. House to improve their diagnostic and clinical skills. At the same time, they are critical enough not to see Dr. House as a role model for their own personality. Well performed medical TV shows such as Dr. House can successfully be used in an educational setting to motivate medical students to come into seminars to learn more about rare diseases.

  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. Editing for performance: Dr Johnson and the stage Editing for performance: Dr Johnson and the stage

    Directory of Open Access Journals (Sweden)

    Peter Hollland

    2008-04-01

    Full Text Available I want to begin by quoting one of Dr Johnson’s notes on Hamlet, a passage that, though entirely characteristic, may be less than familiar to many. Johnson is commenting on the punctuation of a passage and is concerned about a sequence of dashes towards the end of the play: To a literary friend of mine I am indebted for the following very acute observation: “Throughout this play,” says he, “there is nothing more beautiful than these dashes; by their gradual elongation, they distinctly mark the balbuciation and the increasing difficulty of utterance observable in a dying man.” To which let me add, that, although dashes are in frequent use with our tragic poets, yet they are seldom introduced with so good an effect as in the present instance. (qtd. in Wells 1: 69 Johnson’s reliance on others—and their cloaked identity—is something we are used to. So too Johnson’s yearning here both to generalize about tragic practice and to praise the particular local effect in Shakespeare can be paralleled frequently elsewhere. I want to begin by quoting one of Dr Johnson’s notes on Hamlet, a passage that, though entirely characteristic, may be less than familiar to many. Johnson is commenting on the punctuation of a passage and is concerned about a sequence of dashes towards the end of the play: To a literary friend of mine I am indebted for the following very acute observation: “Throughout this play,” says he, “there is nothing more beautiful than these dashes; by their gradual elongation, they distinctly mark the balbuciation and the increasing difficulty of utterance observable in a dying man.” To which let me add, that, although dashes are in frequent use with our tragic poets, yet they are seldom introduced with so good an effect as in the present instance. (qtd. in Wells 1: 69 Johnson’s reliance on others—and their cloaked identity—is something we are used to. So too Johnson’s yearning here both to

  19. 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 .

  20. 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.

  1. 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

  2. 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...

  3. 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.

  4. 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. .

  5. 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.

  6. 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.

  7. 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...

  8. 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

  9. 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)

  10. 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…

  11. 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

  12. Overall properties of the Gaia DR1 reference frame

    Science.gov (United States)

    Liu, N.; Zhu, Z.; Liu, J.-C.; Ding, C.-Y.

    2017-03-01

    Aims: The first Gaia data release (Gaia DR1) provides 2191 ICRF2 sources with their positions in the auxiliary quasar solution and five astrometric parameters - positions, parallaxes, and proper motions - for stars in common between the Tycho-2 catalogue and Gaia in the joint Tycho-Gaia astrometric solution (TGAS). We aim to analyze the overall properties of Gaia DR1 reference frame. Methods: We compare quasar positions of the auxiliary quasar solution with ICRF2 sources using different samples and evaluate the influence on the Gaia DR1 reference frame owing to the Galactic aberration effect over the J2000.0-J2015.0 period. Then we estimate the global rotation between TGAS with Tycho-2 proper motion systems to investigate the property of the Gaia DR1 reference frame. Finally, the Galactic kinematics analysis using the K-M giant proper motions is performed to understand the property of Gaia DR1 reference frame. Results: The positional comparison between the auxiliary quasar solution and ICRF2 shows negligible orientation and validates the declination bias of -0.1mas in Gaia quasar positions with respect to ICRF2. Galactic aberration effect is thought to cause an offset 0.01mas of the Z axis direction of Gaia DR1 reference frame. The global rotation between TGAS and Tycho-2 proper motion systems, obtained by different samples, shows a much smaller value than the claimed value 0.24mas yr-1. For the Galactic kinematics analysis of the TGAS K-M giants, we find possible non-zero Galactic rotation components beyond the classical Oort constants: the rigid part ωYG = -0.38±0.15mas yr-1 and the differential part ω^primeYG = -0.29±0.19mas yr-1 around the YG axis of Galactic coordinates, which indicates possible residual rotation in Gaia DR1 reference frame or problems in the current Galactic kinematical model. Conclusions: The Gaia DR1 reference frame is well aligned to ICRF2, and the possible influence of the Galactic aberration effect should be taken into consideration

  13. 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.

  14. 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.

  15. 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...

  16. 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.

  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. Mainstreaming Culture in Psychology

    Science.gov (United States)

    Cheung, Fanny M.

    2012-01-01

    Despite the "awakening" to the importance of culture in psychology in America, international psychology has remained on the sidelines of psychological science. The author recounts her personal and professional experience in tandem with the stages of development in international/cross-cultural psychology. Based on her research in cross-cultural…

  19. 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...

  20. Tun Dr. Mahathir’s Leadership Communication: The Confucian Perspective

    Directory of Open Access Journals (Sweden)

    Cheah Joyce Lynn-Sze

    2017-01-01

    Full Text Available Previous studies have provided valuable insights into the impact of culture on the concept of leadership communication. However, only a few studies that focused on exploring and understanding the values of Confucianism and its impact on the Chinese culture, especially in Malaysia. Thus, this study is among the first study to examine the leadership communication from the perspective of Confucianism towards the leadership of Dr. Mahathir from the perspective of the Chinese community in Malaysia. This study aims to assess the role of Confucian values in Dr. Mahathir’s leadership communication. This study interviewed 15 Chinese leaders. The findings reveal that three main Confucian values are relevant to Dr. Mahathir’s leadership communication. The Confucian values are Zhi (wisdom, Xin (trust and Xiao (filial piety. This study provides a new perspective on leadership communication from the context of cultural diversity in Malaysia which emphasizes on Confucian values.

  1. HLA Dr beta 1 alleles in Pakistani patients with rheumatoid arthritis

    International Nuclear Information System (INIS)

    Naqi, N.; Ahmed, T.A.; Bashir, M.M.

    2011-01-01

    Objective: To determine frequencies of HLA DR beta 1 alleles in rheumatoid arthritis in Pakistani patients. Study Design: Cross sectional / analytical study. Place and Duration of Study: Department of Immunology, Armed Forces Institute of Pathology, Rawalpindi in collaboration with Rheumatology departments of Military Hospital, Rawalpindi and Fauji Foundation Hospital, Rawalpindi, from January 2009 to January 2010. Methodology: HLA DR beta 1 genotyping of one hundred Pakistani patients, diagnosed as having RA as per American College of Rheumatology revised criteria 1987, was done. HLA DR beta 1 genotyping was carried out at allele group level (DR beta 1*01-DR beta 1*16) by sequence specific primers in RA patients. Comparison of HLA DR beta 1 allele frequencies between patients and control groups was made using Pearson's chi-square test to find possible association of HLA DR?1 alleles with RA in Pakistani rheumatoid patients. Results: HLA DR beta 1*04 was expressed with significantly increased frequency in patients with rheumatoid arthritis (p <0.05). HLA DR?1*11 was expressed statistically significantly more in control group as compared to rheumatoid patients indicating a possible protective effect. There was no statistically significant difference observed in frequencies of HLA DR beta 1 allele *01, DR beta 1 allele *03, DR beta 1 allele *07, DR beta 1 allele *08, DR beta 1 allele *09, DR beta 1 allele *10, DR beta 1 allele *12, DR beta 1 allele *13, DR beta 1 allele *14, DR?1 allele *15 and DR beta 1 allele *16 between patients and control groups. Conclusion: The identification of susceptible HLA DR beta 1 alleles in Pakistani RA patients may help physicians to make early decisions regarding initiation of early intensive therapy with disease modifying anti rheumatic medicines and biological agents decreasing disability in RA patients. (author)

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Professor Bakytzhan Abdiraiym Rector of the L. Gumilov Eurasian National University, Astana, Kazakhstan accompanied by Prof. Kairat Kuterbekov, Dr Bekzat Prmantayeva, Dr Kuralay Maksut with the Director-General, Dr Tadeusz Kurtyka, Adviser for Non-Member States, Mrs Julia Andreeva, Department of Information Technologies and Dr Nikolai Zimine, ATLAS Collaboration, Joint Institute for Nuclear Research, Dubna

    CERN Document Server

    Maximilien Brice

    2011-01-01

    Professor Bakytzhan Abdiraiym Rector of the L. Gumilov Eurasian National University, Astana, Kazakhstan accompanied by Prof. Kairat Kuterbekov, Dr Bekzat Prmantayeva, Dr Kuralay Maksut with the Director-General, Dr Tadeusz Kurtyka, Adviser for Non-Member States, Mrs Julia Andreeva, Department of Information Technologies and Dr Nikolai Zimine, ATLAS Collaboration, Joint Institute for Nuclear Research, Dubna

  8. 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.

  9. 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.

  10. Dr. William O. Coffee and his absorption cure for cataract.

    Science.gov (United States)

    Ferry, A P

    1989-08-01

    Dr. William O. Coffee was an ophthalmologist who conducted an office and mail-order practice in the Midwest from the 1880s until 1927. His main stock in trade was a self-discovered absorption cure for a variety of ocular diseases, with particular emphasis on the medical cure of cataracts. Dr. Coffee's career was a checkered one, marked by dubious credentials, exuberant self-promotion, unlikely and exaggerated claims of medical successes, plagiarism, and rejection by the medical "establishment." Certain parallels may be drawn between his activities and some currently observed practices in ophthalmology.

  11. Dr Jacob van der Land, marine biologist extraordinary

    OpenAIRE

    Bruggen, van, A.C.

    2001-01-01

    This contribution is an attempt to sketch the life and works of Dr Jacob van der Land, curator of worms and chief marine biologist of the National Museum of Natural History, on the occasion of his official retirement. Born in 1935, Jacob van der Land read biology at Leiden University (1958-1964), where he obtained his Ph.D. in 1970 on a treatise on the Priapulida under the supervision of Prof. Dr L.D. Brongersma. In 1964 he was appointed curator of worms in the museum. Later on he took over l...

  12. The Psychological Impact of Awaiting Breast Diagnosis: A Preliminary Picture

    Science.gov (United States)

    Dr. Sweeny is a social psychologist by training, but she applies the theories and methods of social psychology to address patients' experiences with their health and healthcare. Over the years, her work has examined topics ranging from bad news delivery to physician-patient communication to screening decisions. Her current research program focuses on the stressful but understudied experience of awaiting uncertain news, including news about one's health. She developed the uncertainty navigation model as a theoretical framework for understanding the thoughts, feelings, and behaviors that emerge during the wait for health-relevant news. Her work has provided broad and novel insights into this difficult experience, including how waiting experiences unfold over time, the nature of distress during waiting periods, the relative effectiveness of various strategies people can use to cope with uncertainty, and the implications of stressful waiting periods for sleep and health. Dr. Sweeny’s work has been funded by the National Science Foundation and published in top journals, including Annals of Behavioral Medicine, Health Psychology Review, Journal of Personality & Social Psychology, Psychological Bulletin, and Psychological Science. She received the inaugural Early Career Award from the Social Personality Health Network, and in 2016 she was awarded the APA Distinguished Scientific Award for an Early Career Contribution to Health Psychology. In her other life, Dr. Sweeny is a Middle Eastern dance performer and instructor, a yoga enthusiast, and an avid hiker. If you are a person with a disability and require an assistive device, services or other reasonable accommodations to participate in this activity, please contact the Cancer Prevention Fellowship Program at (240) 276-5626 at least one week in advance of the lecture date to discuss your accommodation needs.

  13. 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.

  14. 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

  15. Cognitive psychology and depth psychology backgrounds

    International Nuclear Information System (INIS)

    Fritzsche, A.F.

    1986-01-01

    The sixth chapter gives an insight into the risk perception process which is highly determined by emotions, and, thus, deals with the psychological backgrounds of both the conscious cognitive and the subconscious intuitive realms of the human psyche. The chapter deals with the formation of opinion and the origination of an attitude towards an issue; cognitive-psychological patterns of thinking from the field of risk perception; the question of man's rationality; pertinent aspects of group behaviour; depth psychological backgrounds of the fear of technology; the collective subconscious; nuclear energy as a preferred object of projection for various psychological problems of modern man. (HSCH) [de

  16. Dr. David Sawyer, Mickey Mouse and Dr. David Brown attend a ceremony at Ronald McNair Middle School

    Science.gov (United States)

    1999-01-01

    Dr. David Sawyer (left), Superintendent of the Brevard County School District, Mickey Mouse, and Dr. David Brown, a NASA astronaut, attend a tribute to NASA astronaut Ronald McNair held in the gymnasium of Ronald McNair Magnet School in Cocoa, Fla. During the tribute, Walt Disney World presented a portrait of McNair to the school, which had previously been renamed for the fallen astronaut. McNair was one of a crew of seven who lost their lives during an accident following launch of the Space Shuttle Challenger in January 1986.

  17. 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...

  18. Historizing epistemology in psychology.

    Science.gov (United States)

    Jovanović, Gordana

    2010-12-01

    The conflict between the psychometric methodological framework and the particularities of human experiences reported in psychotherapeutic context led Michael Schwarz to raise the question whether psychology is based on a methodological error. I take this conflict as a heuristic tool for the reconstruction of the early history of psychology, which bears witness to similar epistemological conflicts, though the dominant historiography of psychology has largely forgotten alternative conceptions and their valuable insights into complexities of psychic phenomena. In order to work against the historical amnesia in psychology I suggest to look at cultural-historical contexts which decisively shaped epistemological choices in psychology. Instead of keeping epistemology and history of psychology separate, which nurtures individualism and naturalism in psychology, I argue for historizing epistemology and for historical psychology. From such a historically reflected perspective psychology in contemporary world can be approached more critically.

  19. Psychological Theories of Acculturation

    DEFF Research Database (Denmark)

    Ozer, Simon

    2017-01-01

    advancements, together with greater mobility. Acculturation psychology aims to comprehend the dynamic psychological processes and outcomes emanating from intercultural contact. Acculturation psychology has been a growing field of research within cross-cultural psychology. Today, psychological theories......The proliferation of cultural transition and intercultural contact has highlighted the importance of psychological theories of acculturation. Acculturation, understood as contact between diverse cultural streams, has become prevalent worldwide due to technological, economical, and educational...... of acculturation also include cognate disciplines such as cultural psychology, social psychology, sociology, and anthropology.The expansion of psychological theories of acculturation has led to advancements in the field of research as well as the bifurcation of epistemological and methodological approaches...

  20. Dr. von Braun With a Model of a Launch Vehicle

    Science.gov (United States)

    1950-01-01

    Dr. von Braun stands beside a model of the upper stage (Earth-returnable stage) of the three-stage launch vehicle built for the series of the motion picture productions of space flight produced by Walt Disney in the mid-1950's.

  1. Professor Oberth and Dr. von Braun at ARS Banquet

    Science.gov (United States)

    1961-01-01

    Dr. Wernher von Braun holds the coveted Hermarn Oberth award presented to him by Professor Oberth during the banquet hosted by the Alabama Section of the American Rocket Society (ARS), on October 19, 1961. The Oberth award was given for outstanding technical contributions to the field of astronautics or for the promotion and advancement of astronautical sciences.

  2. Highlight: Dr David Butler-Jones on fighting pandemics | CRDI ...

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

    15 avr. 2016 ... Dr David Butler-Jones, professor in the Faculty of Medicine at the University of Manitoba and former Chief Medical Health Officer of Canada, delivered a lecture on lessons learned from the 2009 flu pandemic in Canada. He also commented on India's draft National Health Policy 2015 at the India ...

  3. Shepard Award Winners, Part 1: Dr. Stephen Thacker

    Centers for Disease Control (CDC) Podcasts

    2009-07-22

    This podcast highlights the accomplishments of Dr. Stephen Thacker, recipient of the prestigious 2009 CDC Charles C. Shepard Award.  Created: 7/22/2009 by Centers for Disease Control and Prevention (CDC).   Date Released: 7/22/2009.

  4. Shepard Award Winners, Part 2: Dr. Tracie Williams

    Centers for Disease Control (CDC) Podcasts

    2009-07-29

    This podcast highlights the accomplishments of Dr. Tracie Williams, recipient of the prestigious 2009 CDC Charles C. Shepard Award.  Created: 7/29/2009 by Centers for Disease Control and Prevention (CDC).   Date Released: 7/29/2009.

  5. Shepard Award Winners, Part 3: Dr. Larissa Roux

    Centers for Disease Control (CDC) Podcasts

    2009-09-22

    This podcast highlights the accomplishments of Dr. Larissa Roux, recipient of the prestigious 2009 CDC Charles C. Shepard Award.  Created: 9/22/2009 by Centers for Disease Control and Prevention (CDC).   Date Released: 9/22/2009.

  6. Researcher Profile: An Interview With Dr. Rebecca J. Travnichek

    Directory of Open Access Journals (Sweden)

    Rebecca J. Travnichek

    2011-04-01

    Full Text Available

    Dr. Rebecca Travnichek is a Family Financial Education Specialist with University of Missouri Extension. Dr. Travnichek currently serves as the Annual Conference Program Chair. She is also very active in the Association for Financial Counseling and Planning Education, where she serves on the Board of Directors. Dr. Travnichek has participated in leadership development programs at the state and national levels. She was involved in the initial proposal development of the Financial Security for All Community of Practice with eXtension and continues to be involved through several roles. She is active in the National Extension Association of Family and Consumer Sciences at the national and state levels, serving in multiple leadership roles. For the past three years, Dr. Travnichek has also served as the Editor of the Journal of the National Extension Association of Family and Consumer Sciences. She represents the type of person who makes the Financial Therapy Association a dynamic organization linking practitioners and academicians.

  7. Rembrandt's anatomy lesson of Dr. Deijman of 1656 dissected

    NARCIS (Netherlands)

    Ijpma, Frank F. A.; Middelkoop, Norbert E.; van Gulik, Thomas M.

    2013-01-01

    More than 350 years ago, Rembrandt painted Anatomy Lesson of Dr. Deijman. This group portrait, featuring important members of the Amsterdam Guild of Surgeons, belongs to the series of paintings of the guild. Rembrandt's masterpiece is one of the most famous historical images of a dissection of the

  8. The Effects of Dr. Oz on Health Behaviors and Attitudes

    Science.gov (United States)

    Crouch, Elizabeth; Dickes, Lori A.; Davis, Amanda; Zarandy, Joy

    2016-01-01

    Background: Consumption of social media has quickly evolved into a primary source of health information for many consumers. This seems to be particularly true for individuals seeking to modify chronic health conditions like weight loss, obesity, and obesity-related diseases. Purpose: This study explores whether watching Dr. Oz weight loss episodes…

  9. Obituary Dr A. W. Kloos (1880—1952)

    NARCIS (Netherlands)

    Ooststroom, van S.J.

    1952-01-01

    At the end of the previous number of “Blumea” could just be inserted the death notice of one of the honorary collaborators of the Rijksherbarium, Dr Ir A. W. Kloos, who passed away in his home at Dordrecht on June 3rd, 1952. A more detailed obituary may follow here. Abraham Willem Kloos was born at

  10. Improving College Students English Learning with Dr. Eye Android Mid

    Science.gov (United States)

    Yang, Ju Yin; Che, Pei-Chun

    2015-01-01

    This paper investigates college students' English language learning through use of Dr. Eye Android handheld mobile Internet device (MID). Compared to related studies, students' English learning using MIDs has not been evaluated and fully understood in the field of higher education. Quantitatively, the researchers used TOEIC pretest and posttest to…

  11. Dr Skateboard's Action Science: Teaching Physics in Context

    Science.gov (United States)

    Robertson, William H.

    2009-01-01

    In order to create student interest and promote new connections to the understanding of fundamental physics concepts, there is a need for new approaches and methods that are both contemporary and relevant. Dr Skateboard's Action Science, a curriculum supplement comprising video instruction and classroom activities, is an example that focuses on…

  12. Dr. Vernon W. Hughes, 81, authority on the subatomic

    CERN Multimedia

    Lavietes, S

    2002-01-01

    "Dr. Vernon W. Hughes, a Yale physicist whose investigation of particles called muons poked holes in standard subatomic theory and provided evidence for the existence of previously undetected matter, died at Yale-New Haven Hospital last Tuesday" (1/2 page).

  13. Dr Jacob van der Land, marine biologist extraordinary

    NARCIS (Netherlands)

    Bruggen, van A.C.

    2001-01-01

    This contribution is an attempt to sketch the life and works of Dr Jacob van der Land, curator of worms and chief marine biologist of the National Museum of Natural History, on the occasion of his official retirement. Born in 1935, Jacob van der Land read biology at Leiden University (1958-1964),

  14. 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.

  15. 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.

  16. 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...

  17. 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.

  18. 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....

  19. 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...

  20. 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, ...

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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

  9. 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.

  10. 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...

  11. 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 ...

  12. 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...

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. Historiography of Czech psychology

    Czech Academy of Sciences Publication Activity Database

    Hoskovcová, S.; Hoskovec, J.; Plháková, A.; Šebek, M.; Švancara, J.; Vobořil, Dalibor

    2010-01-01

    Roč. 13, č. 3 (2010), s. 309-334 ISSN 1093-4510 Institutional research plan: CEZ:AV0Z70250504 Keywords : Czech psychologists * Czechoslovak psychology * ideologic influences on psychology Subject RIV: AN - Psychology Impact factor: 0.500, year: 2010

  19. Teachers and Psychological Reports.

    Science.gov (United States)

    Rogers, George W., Jr.

    The importance of the written psychological report is explored, and, in particular, its relationship to teachers' needs and requirements is discussed. Additionally, the characteristics of a "good" psychological report are listed, and teachers are advised to use these criteria in evaluating the psychological reports they are receiving. (Author)

  20. Psychology in Mexico

    Science.gov (United States)

    Ruiz, Eleonora Rubio

    2011-01-01

    The first formal psychology course taught in Mexico was in 1896 at Mexico's National University; today, National Autonomous University of Mexico (UNAM in Spanish). The modern psychology from Europe and the US in the late 19th century were the primary influences of Mexican psychology, as well as psychoanalysis and both clinical and experimental…

  1. What is Political Psychology?

    Science.gov (United States)

    Deutsch, Morton

    1983-01-01

    Political psychology is the study of the bidirectional interaction of political and psychological processes. This academic discipline was founded after the First World War by Harold D. Lasswell. The content of political psychology is discussed and illustrative studies of the field are briefly summarized. (CS)

  2. Psychology in India

    Science.gov (United States)

    Sushma, B.; Padmaja, G.

    2011-01-01

    Psychology forms the basis of every human activity. The scope of psychology is increasingly widening in various economic, political, social, cultural and technological aspects. Though the application of psychology is extending to various aspects of life, it needs to be indigenised to address the dynamic needs in the various socio-economic contexts…

  3. HLA-DR-expressing cells and T-lymphocytes in sural nerve biopsies

    DEFF Research Database (Denmark)

    Schrøder, H D; Olsson, T; Solders, G

    1988-01-01

    was confirmed. HLA-DR expression was found in all biopsies and thus was not restricted to any particular type of neuropathy. The HLA-DR expression appeared to correlate with severity and activity of the neuropathy. HLA-DR-expressing macrophages wrapping myelinated fibers were prominent in primary demyelinating......Thirty-five sural nerve biopsies were stained immunohistochemically for HLA-DR antigen. HLA-DR was expressed on nonmyelinating Schwann cells, macrophages, vascular endothelium, and perineurium. By means of double immunofluorescence staining the identity of the HLA-DR presenting structures...

  4. 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.

  5. 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....

  6. 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...

  7. Optimization on scoliosis examination on Canons DR system

    DEFF Research Database (Denmark)

    Precht, Helle

    2007-01-01

    recordings of scoliosis today are carried out on CR systems even though most radiological departments have DR systems available. Theoretically speaking the two modalities are similar regarding dose and image quality. In this project consequently, the focus will be to obtain images of equal dose and quality...... at a DR system when using different receptors during the exam. This is a completely new opportunity, as it has earlier been difficult to compare distinct scintilators connected to the receptors due to unlike processing of the image. Given that Canon have released a receptor with CsI scintilator we...... in which theory is used as a background for the test setup and later audit appraisal. Two tests are carried out on two different hospitals with each their receptor, and afterwards the results are compared. To guarantee comparable tests the results are verified through status checks and statistical t...

  8. Dr. Harry Whelan With the Light Emitting Diode Probe

    Science.gov (United States)

    1999-01-01

    The red light from the Light Emitting Diode (LED) probe shines through the fingers of Dr. Harry Whelan, a pediatric neurologist at the Children's Hospital of Wisconsin in Milwaukee. Dr. Whelan uses the long waves of light from the LED surgical probe to activate special drugs that kill brain tumors. Laser light previously has been used for this type of surgery, but the LED light illuminates through all nearby tissues, reaching parts of tumors that shorter wavelengths of laser light carnot. The new probe is safer because the longer wavelengths of light are cooler than the shorter wavelengths of laser light, making the LED less likely to injure normal brain tissue near the tumor. Also, it can be used for hours at a time while still remaining cool to the touch. The probe was developed for photodynamic cancer therapy under a NASA Small Business Innovative Research Program grant. The program is part of NASA's Technology Transfer Department at the Marshall Space Flight Center.

  9. INTAS Secretary General Dr. J. Sinnaeve visiting Athena experiment.

    CERN Multimedia

    Patrice Loiez

    2002-01-01

    Photo 1: INTAS Secretary General Dr. J. Sinnaeve, N. Koulberg, Prof. H. Bokemeyer Head of Physics at INTAS, D.O.Williams and Rolf Landua visiting ATHENA. Photo 2: Prof. H. Bokemeyer Head of Physics at INTAS, INTAS Secretary General J. Sinnaeve and Rolf Landua visiting ATHENA. Photo 3: In the control room of ATHENA, Rolf Landua, Prof. H. Bokemeyer Head of Physics at INTAS and INTAS Secretary General Dr. J. Sinnaeve. INTAS is an independent International Association formed by the European Community, European Union´s Member States and like minded countries acting to preserve and promote the valuable scientific potential of the NIS partner countries through East-West Scientific co-operation.

  10. DR Experiments in the 60 years since the Bates paper

    International Nuclear Information System (INIS)

    Johnsen, Rainer

    2011-01-01

    About 60 years have passed since David Bates in a 1950 Physical Review Letter to the Editor first clarified the dissociative recombination mechanism (DR) of molecular ions and provided the conceptual basis for the process that plays an important role in the ionospheres of Earth and other planets, the interstellar medium, and electrical discharges. His visionary (and characteristically 'terse') thumbnail sketch of the DR mechanism only hinted at the subtleties that have kept atomic theorists and experimentalists busy for many years. In my talk, I will focus on experiments on N 2 + recombination, beginning with plasma afterglows, and then move on to the 'after'-afterglow period that is now dominated by the powerful storage-ring methods.

  11. N2R vs. DR Network Infrastructure Evaluation

    DEFF Research Database (Denmark)

    Pedersen, Jens Myrup; Roost, Lars Jessen; Toft, Per Nesager

    2007-01-01

    Recent development of Internet-based services has set higher requirements to network infrastructures in terms of more bandwidth, lower delays and more reliability. Theoretical research within the area of Structural Quality of Service (SQoS) has introduced a new type of infrastructure which meet...... these requirements: N2R infrastructures. This paper contributes to the ongoing research with a case study from North Jutland. An evaluation of three N2R infrastructures compared to a Double Ring (DR) infrastructure will provide valuable information of the practical applicability of N2R infrastructures. In order...... to study if N2R infrastructures perform better than the DR infrastructure, a distribution network was established based on geographical information system (GIS) data. Nodes were placed with respect to demographic and geographical factors. The established distribution network was investigated with respect...

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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...

  19. DR services in Fiji: attitudes, barriers and screening practices

    Directory of Open Access Journals (Sweden)

    Bridget Kool

    2015-06-01

    Full Text Available The aim of this study was to describe the attitudes and perceptions of primary health care doctors in Fiji regarding the importance of eye care in diabetes mellitus (DM management, to explore current eye care practice, and to investigate awareness and use of relevant clinical practice guidelines. The study builds on earlier research conducted in Fiji that identified a rapid increase of late-stage DR patients presenting for treatment, at a time when surgery was the only option.

  20. Postdoctoral Fellowship for Dr. Lindholm, Underwater Physiology and Medicine

    Science.gov (United States)

    2008-05-01

    hypoxia close to loss of consciousness during apnea seems to be of similar intensity as in the "steady state" situation of hypobaric hypoxia during...for outstanding scientific contribution to advances in the undersea or hyperbaric biomedical field 2006 4. Pendergast DR: Honoree of the SUNY Research...2. Lindholm P and Lundgren CEG. Alveolar gas composition before and after maximal breath-holds in competitive divers. , Undersea and Hyperbaric

  1. Tun Dr. Mahathir’s Leadership Communication: The Confucian Perspective

    OpenAIRE

    Cheah Joyce Lynn-Sze; Yusof Norhafezah; Ahmad Mohd Khairie

    2017-01-01

    Previous studies have provided valuable insights into the impact of culture on the concept of leadership communication. However, only a few studies that focused on exploring and understanding the values of Confucianism and its impact on the Chinese culture, especially in Malaysia. Thus, this study is among the first study to examine the leadership communication from the perspective of Confucianism towards the leadership of Dr. Mahathir from the perspective of the Chinese community in Malaysia...

  2. 105-DR Large Sodium Fire Facility closure plan

    International Nuclear Information System (INIS)

    1993-05-01

    The Hanford Site, located northwest of the city of Richland, Washington, houses reactors, chemical-separation systems, and related facilities used for the production of special nuclear materials, and activities associated with nuclear energy development. The 105-DR Large Sodium Fire Facility (LSFF), which was in operation from about 1972 to 1986, was a research laboratory that occupied the former ventilation supply room on the southwest side of the 105-DR Reactor facility. The LSFF was established to provide a means of investigating fire and safety aspects associated with large sodium or other metal alkali fires in the liquid metal fast breeder reactor (LMFBR) facilities. The 105-DR Reactor facility was designed and built in the 1950's and is located in the 100-D Area of the Hanford Site. The building housed the 105-DR defense reactor, which was shut down in 1964. The LSFF was initially used only for engineering-scale alkali metal reaction studies. In addition, the Fusion Safety Support Studies program sponsored intermediate-size safety reaction tests in the LSFF with lithium and lithium lead compounds. The facility has also been used to store and treat alkali metal waste, therefore the LSFF is subject to the regulatory requirements for the storage and treatment of dangerous waste. Closure will be conducted pursuant to the requirements of the Washington Administrative Code (WAC) 173-303-610. This closure plan presents a description of the facility, the history of waste managed, and the procedures that will be followed to close the LSFF as an Alkali Metal Treatment Facility. No future use of the LSFF is expected

  3. 105-DR Large Sodium Fire Facility closure activities evaluation report

    International Nuclear Information System (INIS)

    Adler, J.G.

    1996-01-01

    This report evaluates the closure activities at the 105-DR Large Sodium Fire Facility. The closure activities discussed include: the closure activities for the structures, equipment, soil, and gravel scrubber; decontamination methods; materials made available for recycling or reuse; and waste management. The evaluation compares these activities to the regulatory requirements and closure plan requirements. The report concludes that the areas identified in the closure plan can be clean closed

  4. 105-DR Large Sodium Fire Facility closure plan. Revision 1

    Energy Technology Data Exchange (ETDEWEB)

    1993-05-01

    The Hanford Site, located northwest of the city of Richland, Washington, houses reactors, chemical-separation systems, and related facilities used for the production of special nuclear materials, and activities associated with nuclear energy development. The 105-DR Large Sodium Fire Facility (LSFF), which was in operation from about 1972 to 1986, was a research laboratory that occupied the former ventilation supply room on the southwest side of the 105-DR Reactor facility. The LSFF was established to provide a means of investigating fire and safety aspects associated with large sodium or other metal alkali fires in the liquid metal fast breeder reactor (LMFBR) facilities. The 105-DR Reactor facility was designed and built in the 1950`s and is located in the 100-D Area of the Hanford Site. The building housed the 105-DR defense reactor, which was shut down in 1964. The LSFF was initially used only for engineering-scale alkali metal reaction studies. In addition, the Fusion Safety Support Studies program sponsored intermediate-size safety reaction tests in the LSFF with lithium and lithium lead compounds. The facility has also been used to store and treat alkali metal waste, therefore the LSFF is subject to the regulatory requirements for the storage and treatment of dangerous waste. Closure will be conducted pursuant to the requirements of the Washington Administrative Code (WAC) 173-303-610. This closure plan presents a description of the facility, the history of waste managed, and the procedures that will be followed to close the LSFF as an Alkali Metal Treatment Facility. No future use of the LSFF is expected.

  5. ORAC-DR: A generic data reduction pipeline infrastructure

    Science.gov (United States)

    Jenness, Tim; Economou, Frossie

    2015-03-01

    ORAC-DR is a general purpose data reduction pipeline system designed to be instrument and observatory agnostic. The pipeline works with instruments as varied as infrared integral field units, imaging arrays and spectrographs, and sub-millimeter heterodyne arrays and continuum cameras. This paper describes the architecture of the pipeline system and the implementation of the core infrastructure. We finish by discussing the lessons learned since the initial deployment of the pipeline system in the late 1990s.

  6. 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.

  7. 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.

  8. Cas3 is a single-stranded DNA nuclease and ATP-dependent helicase in the CRISPR/Cas immune system.

    Science.gov (United States)

    Sinkunas, Tomas; Gasiunas, Giedrius; Fremaux, Christophe; Barrangou, Rodolphe; Horvath, Philippe; Siksnys, Virginijus

    2011-04-06

    Clustered regularly interspaced short palindromic repeat (CRISPR) is a recently discovered adaptive prokaryotic immune system that provides acquired immunity against foreign nucleic acids by utilizing small guide crRNAs (CRISPR RNAs) to interfere with invading viruses and plasmids. In Escherichia coli, Cas3 is essential for crRNA-guided interference with virus proliferation. Cas3 contains N-terminal HD phosphohydrolase and C-terminal Superfamily 2 (SF2) helicase domains. Here, we provide the first report of the cloning, expression, purification and in vitro functional analysis of the Cas3 protein of the Streptococcus thermophilus CRISPR4 (Ecoli subtype) system. Cas3 possesses a single-stranded DNA (ssDNA)-stimulated ATPase activity, which is coupled to unwinding of DNA/DNA and RNA/DNA duplexes. Cas3 also shows ATP-independent nuclease activity located in the HD domain with a preference for ssDNA substrates. To dissect the contribution of individual domains, Cas3 separation-of-function mutants (ATPase(+)/nuclease(-) and ATPase(-)/nuclease(+)) were obtained by site-directed mutagenesis. We propose that the Cas3 ATPase/helicase domain acts as a motor protein, which assists delivery of the nuclease activity to Cascade-crRNA complex targeting foreign DNA.

  9. Practitioner Profile: An Interview with Dr. Jerry Gale, LMFT

    Directory of Open Access Journals (Sweden)

    Jerry Gale

    2012-06-01

    Full Text Available Dr. Jerry Gale is an Associate Professor and the Clinical Director of the Marriage and Family Therapy Doctoral Program at the University of Georgia. He is a Licensed Marriage and Family Therapist and an approved supervisor of the American Association of Marriage and Family Therapists. He earned a B.A. from the University of Michigan, a MEd from the University of Arizona, and a Ph.D. from Texas Tech University. Over the course of his career, Dr. Gale has authored three books and over 60 articles and book chapters. He is a co-developer of a relational financial therapy approach that combines financial counseling with family therapy and has extensive training in clinical hypnosis, couples therapy, and family therapy, as well as mindfulness meditation. He is the recipient of the American Family Therapy Academy 2006 Outstanding Research Award. In addition to his work at the University of Georgia, Dr. Gale conducts therapy at Athens Associates for Counseling and Psychotherapy.

  10. Dr.LiTHO: a development and research lithography simulator

    Science.gov (United States)

    Fühner, Tim; Schnattinger, Thomas; Ardelean, Gheorghe; Erdmann, Andreas

    2007-03-01

    This paper introduces Dr.LiTHO, a research and development oriented lithography simulation environment developed at Fraunhofer IISB to flexibly integrate our simulation models into one coherent platform. We propose a light-weight approach to a lithography simulation environment: The use of a scripting (batch) language as an integration platform. Out of the great variety of different scripting languages, Python proved superior in many ways: It exhibits a good-natured learning-curve, it is efficient, available on virtually any platform, and provides sophisticated integration mechanisms for existing programs. In this paper, we will describe the steps, required to provide Python bindings for existing programs and to finally generate an integrated simulation environment. In addition, we will give a short introduction into selected software design demands associated with the development of such a framework. We will especially focus on testing and (both technical and user-oriented) documentation issues. Dr.LiTHO Python files contain not only all simulation parameter settings but also the simulation flow, providing maximum flexibility. In addition to relatively simple batch jobs, repetitive tasks can be pooled in libraries. And as Python is a full-blown programming language, users can add virtually any functionality, which is especially useful in the scope of simulation studies or optimization tasks, that often require masses of evaluations. Furthermore, we will give a short overview of the numerous existing Python packages. Several examples demonstrate the feasibility and productiveness of integrating Python packages into custom Dr.LiTHO scripts.

  11. Relationship between drug resistance and the clustered, regularly interspaced, short, palindromic repeat-associated protein genes cas1 and cas2 in Shigella from giant panda dung.

    Science.gov (United States)

    Ren, Lu; Deng, Lin-Hua; Zhang, Ri-Peng; Wang, Cheng-Dong; Li, De-Sheng; Xi, Li-Xin; Chen, Zhen-Rong; Yang, Rui; Huang, Jie; Zeng, Yang-Ru; Wu, Hong-Lin; Cao, San-Jie; Wu, Rui; Huang, Yong; Yan, Qi-Gui

    2017-02-01

    To detect drug resistance in Shigella obtained from the dung of the giant panda, explore the factors leading to drug resistance in Shigella, understand the characteristics of clustered, regularly interspaced, short, palindromic repeats (CRISPR), and assess the relationship between CRISPR and drug resistance. We collected fresh feces from 27 healthy giant pandas in the Giant Panda Conservation base (Wolong, China). We identified the strains of Shigella in the samples by using nucleotide sequence analysis. Further, the Kirby-Bauer paper method was used to determine drug sensitivity of the Shigella strains. CRISPR-associated protein genes cas1 and cas2 in Shigella were detected by polymerase chain reaction (PCR), and the PCR products were sequenced and compared. We isolated and identified 17 strains of Shigella from 27 samples, including 14 strains of Shigella flexneri, 2 strains of Shigella sonnei, and 1 strain of Shigella dysenteriae. Further, drug resistance to cefazolin, imipenem, and amoxicillin-clavulanic acid was identified as a serious problem, as multidrug-resistant strains were detected. Further, cas1 and cas2 showed different degrees of point mutations. The CRISPR system widely exists in Shigella and shares homology with that in Escherichia coli. The cas1 and cas 2 mutations contribute to the different levels of resistance. Point mutations at sites 3176455, 3176590, and 3176465 in cas1 (a); sites 3176989, 3176992, and 3176995 in cas1 (b); sites 3176156 and 3176236 in cas2 may affect the resistance of bacteria, cause emergence of multidrug resistance, and increase the types of drug resistance.

  12. Dr. Lindberg's Legacy : Charting A New Course | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... more. Don also created the National Center for Biotechnology Information (NCBI). NCBI has been a focal point ... with Dr. Lindberg (right) and National Center for Biotechnology Information Director Dr. David Lipman (center) at a ...

  13. Assaying Break and Nick-Induced Homologous Recombination in Mammalian Cells Using the DR-GFP Reporter and Cas9 Nucleases

    NARCIS (Netherlands)

    Vriend, Lianne E. M.; Jasin, Maria; Krawczyk, Przemek M.

    2014-01-01

    Thousands of DNA breaks occur daily in mammalian cells, including potentially tumorigenic double-strand breaks (DSBs) and less dangerous but vastly more abundant single-strand breaks (SSBs). The majority of SSBs are quickly repaired, but some can be converted to DSBs, posing a threat to the

  14. Survey of clustered regularly interspaced short palindromic repeats and their associated Cas proteins (CRISPR/Cas) systems in multiple sequenced strains of Klebsiella pneumoniae.

    Science.gov (United States)

    Ostria-Hernández, Martha Lorena; Sánchez-Vallejo, Carlos Javier; Ibarra, J Antonio; Castro-Escarpulli, Graciela

    2015-08-04

    In recent years the emergence of multidrug resistant Klebsiella pneumoniae strains has been an increasingly common event. This opportunistic species is one of the five main bacterial pathogens that cause hospital infections worldwide and multidrug resistance has been associated with the presence of high molecular weight plasmids. Plasmids are generally acquired through horizontal transfer and therefore is possible that systems that prevent the entry of foreign genetic material are inactive or absent. One of these systems is CRISPR/Cas. However, little is known regarding the clustered regularly interspaced short palindromic repeats and their associated Cas proteins (CRISPR/Cas) system in K. pneumoniae. The adaptive immune system CRISPR/Cas has been shown to limit the entry of foreign genetic elements into bacterial organisms and in some bacteria it has been shown to be involved in regulation of virulence genes. Thus in this work we used bioinformatics tools to determine the presence or absence of CRISPR/Cas systems in available K. pneumoniae genomes. The complete CRISPR/Cas system was identified in two out of the eight complete K. pneumoniae genomes sequences and in four out of the 44 available draft genomes sequences. The cas genes in these strains comprises eight cas genes similar to those found in Escherichia coli, suggesting they belong to the type I-E group, although their arrangement is slightly different. As for the CRISPR sequences, the average lengths of the direct repeats and spacers were 29 and 33 bp, respectively. BLAST searches demonstrated that 38 of the 116 spacer sequences (33%) are significantly similar to either plasmid, phage or genome sequences, while the remaining 78 sequences (67%) showed no significant similarity to other sequences. The region where the CRISPR/Cas systems were located is the same in all the Klebsiella genomes containing it, it has a syntenic architecture, and is located among genes encoding for proteins likely involved in

  15. Granice podmorskih prostora jadranskih država

    Directory of Open Access Journals (Sweden)

    Marina Vokić Žužul

    2015-09-01

    Full Text Available U ovome radu analiziraju se sve dosada utvrđene granice jadranskog podmorja kao i one koje tak valja utvrditi, posebice u svjetlu novih istraživanja njegovih prirodnih bogatstava. Uz Hrvatsku i Italiju, koje dijele najveći dio morskog dna i podzemlja u Jadranu, pravo na epikontinentski pojas imaju i Crna Gora te Albanija. Dvije jadranske države s kratkim obalama – Bosna i Hercegovina te Slovenija, države su u nepovoljnome geografskom položaju koje ne mogu imati epikontinentski pojas kao prirodni produžetak svoga kopnenog područja. Podmorski prostori tih država završavaju stoga na vanjskoj granici njihovih teritorijalnih mora. Osim razmatranja tih granica i sporazumno utvrđenih granica epikontinentskih pojaseva, autorice se kritički osvrću i na jednostrane akte Slovenije o proglašenju njezinoga epikontinentskog pojasa iz 2005. godine kao potpuno pravno neutemeljene akte. U središtu pozornosti ovoga rada je razmatranje granice koja dijeli podmorske prostore Hrvatske i Italije kao buduće granice dviju država i nad morskim dnom. Ta bi granična crta, u skladu s Konvencijom UN-a o pravu mora, trebala postati – jedinstvena morska granica njihovih epikontinentskih i gospodarskih pojaseva (odnosno ekološke zone Italije i zaštićenoga ekološko-ribolovnog pojasa Republike Hrvatske. Takva višefunkcionalna jedinstvena granična crta u najboljem je interesu pravne sigurnosti u svim načinima korištenja mora, a u međunarodnoj sudskoj i arbitražnoj praksi posljednjih desetljeća u potpunosti je zamijenila povlačenje različitih crta razgraničenja za više pojaseva u istome morskom prostoru. S obzirom na rezultate nedavno provedenih istraživanja potencijalnih nalazišta nafte i plina u južnom Jadranu, u radu se upozorava i na potrebu što skorijeg povlačenja crte bočnog razgraničenja epikontinentskih pojaseva Hrvatske i Crne Gore. Autorice analiziraju moguće pravce te nove granice, uzimajući u obzir znatno odstupanje od

  16. CRISPR/Cas9: at the cutting edge of hepatology

    Science.gov (United States)

    Pankowicz, Francis P; Jarrett, Kelsey E; Lagor, William R; Bissig, Karl-Dimiter

    2018-01-01

    Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 genome engineering has revolutionised biomedical science and we are standing on the cusp of medical transformation. The therapeutic potential of this technology is tremendous, however, its translation to the clinic will be challenging. In this article, we review recent progress using this genome editing technology and explore its potential uses in studying and treating diseases of the liver. We discuss the development of new research tools and animal models as well as potential clinical applications, strategies and challenges. PMID:28487442

  17. CRISPR-Cas: evolution of an RNA-based adaptive immunity system in prokaryotes.

    Science.gov (United States)

    Koonin, Eugene V; Makarova, Kira S

    2013-05-01

    The CRISPR-Cas (clustered regularly interspaced short palindromic repeats, CRISPR-associated genes) is an adaptive immunity system in bacteria and archaea that functions via a distinct self-non-self recognition mechanism that is partially analogous to the mechanism of eukaryotic RNA interference (RNAi). The CRISPR-Cas system incorporates fragments of virus or plasmid DNA into the CRISPR repeat cassettes and employs the processed transcripts of these spacers as guide RNAs to cleave the cognate foreign DNA or RNA. The Cas proteins, however, are not homologous to the proteins involved in RNAi and comprise numerous, highly diverged families. The majority of the Cas proteins contain diverse variants of the RNA recognition motif (RRM), a widespread RNA-binding domain. Despite the fast evolution that is typical of the cas genes, the presence of diverse versions of the RRM in most Cas proteins provides for a simple scenario for the evolution of the three distinct types of CRISPR-cas systems. In addition to several proteins that are directly implicated in the immune response, the cas genes encode a variety of proteins that are homologous to prokaryotic toxins that typically possess nuclease activity. The predicted toxins associated with CRISPR-Cas systems include the essential Cas2 protein, proteins of COG1517 that, in addition to a ligand-binding domain and a helix-turn-helix domain, typically contain different nuclease domains and several other predicted nucleases. The tight association of the CRISPR-Cas immunity systems with predicted toxins that, upon activation, would induce dormancy or cell death suggests that adaptive immunity and dormancy/suicide response are functionally coupled. Such coupling could manifest in the persistence state being induced and potentially providing conditions for more effective action of the immune system or in cell death being triggered when immunity fails.

  18. Mobile Genetic Elements and Evolution of CRISPR-Cas Systems: All the Way There and Back

    Science.gov (United States)

    Makarova, Kira S.

    2017-01-01

    Abstract The Clustered Regularly Interspaced Palindromic Repeats (CRISPR)-CRISPR-associated proteins (Cas) systems of bacterial and archaeal adaptive immunity show multifaceted evolutionary relationships with at least five classes of mobile genetic elements (MGE). First, the adaptation module of CRISPR-Cas that is responsible for the formation of the immune memory apparently evolved from a Casposon, a self-synthesizing transposon that employs the Cas1 protein as the integrase and might have brought additional cas genes to the emerging immunity loci. Second, a large subset of type III CRISPR-Cas systems recruited a reverse transcriptase from a Group II intron, providing for spacer acquisition from RNA. Third, effector nucleases of Class 2 CRISPR-Cas systems that are responsible for the recognition and cleavage of the target DNA were derived from transposon-encoded TnpB nucleases, most likely, on several independent occasions. Fourth, accessory nucleases in some variants of types I and III toxin and type VI effectors RNases appear to be ultimately derived from toxin nucleases of microbial toxin–antitoxin modules. Fifth, the opposite direction of evolution is manifested in the recruitment of CRISPR-Cas systems by a distinct family of Tn7-like transposons that probably exploit the capacity of CRISPR-Cas to recognize unique DNA sites to facilitate transposition as well as by bacteriophages that employ them to cope with host defense. Additionally, individual Cas proteins, such as the Cas4 nuclease, were recruited by bacteriophages and transposons. The two-sided evolutionary connection between CRISPR-Cas and MGE fits the “guns for hire” paradigm whereby homologous enzymatic machineries, in particular nucleases, are shuttled between MGE and defense systems and are used alternately as means of offense or defense. PMID:28985291

  19. For Dr. Nancy Snyderman's Parents, Staying Close to Family Is Key

    Science.gov (United States)

    ... to move closer to their daughter and her family, as part of the next chapter in their lives. Photo courtesy of Dr. Nancy Snyderman As Chief Medical Editor for NBC News and host of the popular MSNBC show, Dr. Nancy , Dr. ...

  20. Agonistic Human Monoclonal Antibodies against Death Receptor 4 (DR4) | NCI Technology Transfer Center | TTC

    Science.gov (United States)

    The National Cancer Institute is seeking parties interested in licensing human monoclonal antibodies (mAbs) that bind to death receptor 4 ("DR4"). The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and its functional receptors, DR4 and DR5, have been recognized as promising targets for cancer treatment.

  1. Human immune responsiveness to Lolium perenne pollen allergen Lol p III (rye III) is associated with HLA-DR3 and DR5.

    Science.gov (United States)

    Ansari, A A; Freidhoff, L R; Meyers, D A; Bias, W B; Marsh, D G

    1989-05-01

    A well-characterized allergen of Lolium perenne (perennial rye grass) pollen, Lol p III, has been used as a model antigen to study the genetic control of the human immune response. Associations between HLA type and IgE or IgG antibody (Ab) responsiveness to Lol p III were studied in two groups of skin-test-positive Caucasoid adults (N = 135 and 67). We found by nonparametric and parametric analyses that immune responsiveness to Lol p III was significantly associated with HLA-DR3 and DR5. No association was found between any DQ type and immune responsiveness to Lol p III. Geometric mean IgE or IgG Ab levels to Lol p III were not different between B8+, DR3+ subjects and B8-, DR3+ subjects, showing that HLA-B8 had no influence on the association. Lol p III IgG Ab data obtained on subjects after grass antigen immunotherapy showed that 100% of DR3 subjects and 100% of DR5 subjects were Ab+. A comparison of all the available protein sequences of DRB gene products showed that the first hypervariable region of DR3 and DR5 (and DRw6), and no other region, contains the sequence Glu9-Tyr-Ser-Thr-Ser13. Our observations are consistent with the possibility that immune responsiveness to the allergen Lol p III is associated with this amino acid sequence in the first hypervariable region of the DR beta 1 polypeptide chain.

  2. Engineering resistance against Tomato yellow leaf curl virus via the CRISPR/Cas9 system in tomato

    KAUST Repository

    Mahfouz, Magdy M.; Tashkandi, Manal; Ali, Zahir; Aljedaani, Fatimah R.; Shami, Ashwag

    2017-01-01

    CRISPR/Cas systems confer molecular immunity against phages and conjugative plasmids in prokaryotes. Recently, CRISPR/Cas9 systems have been used to confer interference against eukaryotic viruses. Here, we engineered Nicotiana benthamiana and tomato

  3. Ethnographic Fieldwork in psychology

    DEFF Research Database (Denmark)

    Tanggaard, Lene

    2014-01-01

    It is argued in the present article that ethnographic fieldwork can serve useful methodological ends within psychology and open the discipline to the cultural landscape of psychological phenomena in everyday life in social practices. Furthermore, a positive case is made for the soundness...... of ethnographic fieldwork. That is, rather than disputing the claim that qualitative methods can serve scientific ends, it is argued that ethnographic fieldwork is suitable for studying the constitution of psychological phenomena in social practices across time....

  4. Psychology and criminal justice

    OpenAIRE

    Adler, Joanna R.

    2013-01-01

    This chapter is designed to give the reader a flavour of a few areas in which psychology has been applied to criminal justice. It begins by providing some historical context and showing the development of some applications of psychology to criminal justice. The chapter is broadly split into 3 sections: Pre Trial; Trial; and Post Trial. In most of this chapter, the areas considered assess how psychology has had an influence on the law and how psychologists work within criminal justice settings...

  5. Strategic Psychological Operations management

    OpenAIRE

    Sokoloski, Joseph A.

    2005-01-01

    United States Military Psychological Operations are engaged in a type of mass marketing of ideas. To accomplish this The United States Army Civil Affairs and Psychological Operations Command (USACAPOC) employs active and reserve PSYOP units to conduct PSYOP campaigns. However the methodology used to manage these campaigns often hinders the effective employment of timely and effective Psychological Operations. PSYOP has a difficult job to accomplish but PSYOP does not have the proper managemen...

  6. Baculoviral delivery of CRISPR/Cas9 facilitates efficient genome editing in human cells

    NARCIS (Netherlands)

    Hindriksen, Sanne; Bramer, Arne J; Truong, My Anh; Vromans, Martijn J M; Post, Jasmin B; Verlaan-Klink, Ingrid; Snippert, Hugo J; Lens, Susanne M A; Hadders, Michael A

    2017-01-01

    The CRISPR/Cas9 system is a highly effective tool for genome editing. Key to robust genome editing is the efficient delivery of the CRISPR/Cas9 machinery. Viral delivery systems are efficient vehicles for the transduction of foreign genes but commonly used viral vectors suffer from a limited

  7. 76 FR 79545 - Cost Accounting Standards: Change to the CAS Applicability Threshold for the Inflation Adjustment...

    Science.gov (United States)

    2011-12-22

    ... Cost Accounting Standards: Change to the CAS Applicability Threshold for the Inflation Adjustment to... Federal Procurement Policy, Cost Accounting Standards Board. ACTION: Final rule. SUMMARY: The Office of Federal Procurement Policy (OFPP), Cost Accounting Standards (CAS) Board (Board), has adopted, without...

  8. Computational Neural Modeling of Speech Motor Control in Childhood Apraxia of Speech (CAS)

    Science.gov (United States)

    Terband, Hayo; Maassen, Ben; Guenther, Frank H.; Brumberg, Jonathan

    2009-01-01

    Purpose: Childhood apraxia of speech (CAS) has been associated with a wide variety of diagnostic descriptions and has been shown to involve different symptoms during successive stages of development. In the present study, the authors attempted to associate the symptoms of CAS in a particular developmental stage with particular…

  9. Phonological Awareness and Early Reading Development in Childhood Apraxia of Speech (CAS)

    Science.gov (United States)

    McNeill, B. C.; Gillon, G. T.; Dodd, B.

    2009-01-01

    Background: Childhood apraxia of speech (CAS) is associated with phonological awareness, reading, and spelling deficits. Comparing literacy skills in CAS with other developmental speech disorders is critical for understanding the complexity of the disorder. Aims: This study compared the phonological awareness and reading development of children…

  10. Computational neural modeling of speech motor control in childhood apraxia of speech (CAS).

    NARCIS (Netherlands)

    Terband, H.R.; Maassen, B.A.M.; Guenther, F.H.; Brumberg, J.

    2009-01-01

    PURPOSE: Childhood apraxia of speech (CAS) has been associated with a wide variety of diagnostic descriptions and has been shown to involve different symptoms during successive stages of development. In the present study, the authors attempted to associate the symptoms of CAS in a particular

  11. An Undergraduate Laboratory Class Using CRISPR/Cas9 Technology to Mutate Drosophila Genes

    Science.gov (United States)

    Adame, Vanesa; Chapapas, Holly; Cisneros, Marilyn; Deaton, Carol; Deichmann, Sophia; Gadek, Chauncey; Lovato, TyAnna L.; Chechenova, Maria B.; Guerin, Paul; Cripps, Richard M.

    2016-01-01

    CRISPR/Cas9 genome editing technology is used in the manipulation of genome sequences and gene expression. Because of the ease and rapidity with which genes can be mutated using CRISPR/Cas9, we sought to determine if a single-semester undergraduate class could be successfully taught, wherein students isolate mutants for specific genes using…

  12. Efficient fdCas9 Synthetic Endonuclease with Improved Specificity for Precise Genome Engineering

    KAUST Repository

    Aouida, Mustapha; Eid, Ayman; Ali, Zahir; Cradick, Thomas; Lee, Ciaran; Deshmukh, Harshavardhan; Atef, Ahmed; Abu Samra, Dina Bashir Kamil; Gadhoum, Samah Zeineb; Merzaban, Jasmeen; Bao, Gang; Mahfouz, Magdy M.

    2015-01-01

    The Cas9 endonuclease is used for genome editing applications in diverse eukaryotic species. A high frequency of off-target activity has been reported in many cell types, limiting its applications to genome engineering, especially in genomic medicine. Here, we generated a synthetic chimeric protein between the catalytic domain of the FokI endonuclease and the catalytically inactive Cas9 protein (fdCas9). A pair of guide RNAs (gRNAs) that bind to sense and antisense strands with a defined spacer sequence range can be used to form a catalytically active dimeric fdCas9 protein and generate double-strand breaks (DSBs) within the spacer sequence. Our data demonstrate an improved catalytic activity of the fdCas9 endonuclease, with a spacer range of 15–39 nucleotides, on surrogate reporters and genomic targets. Furthermore, we observed no detectable fdCas9 activity at known Cas9 off-target sites. Taken together, our data suggest that the fdCas9 endonuclease variant is a superior platform for genome editing applications in eukaryotic systems including mammalian cells.

  13. p53 inhibits CRISPR-Cas9 engineering in human pluripotent stem cells.

    Science.gov (United States)

    Ihry, Robert J; Worringer, Kathleen A; Salick, Max R; Frias, Elizabeth; Ho, Daniel; Theriault, Kraig; Kommineni, Sravya; Chen, Julie; Sondey, Marie; Ye, Chaoyang; Randhawa, Ranjit; Kulkarni, Tripti; Yang, Zinger; McAllister, Gregory; Russ, Carsten; Reece-Hoyes, John; Forrester, William; Hoffman, Gregory R; Dolmetsch, Ricardo; Kaykas, Ajamete

    2018-06-11

    CRISPR/Cas9 has revolutionized our ability to engineer genomes and conduct genome-wide screens in human cells 1-3 . Whereas some cell types are amenable to genome engineering, genomes of human pluripotent stem cells (hPSCs) have been difficult to engineer, with reduced efficiencies relative to tumour cell lines or mouse embryonic stem cells 3-13 . Here, using hPSC lines with stable integration of Cas9 or transient delivery of Cas9-ribonucleoproteins (RNPs), we achieved an average insertion or deletion (indel) efficiency greater than 80%. This high efficiency of indel generation revealed that double-strand breaks (DSBs) induced by Cas9 are toxic and kill most hPSCs. In previous studies, the toxicity of Cas9 in hPSCs was less apparent because of low transfection efficiency and subsequently low DSB induction 3 . The toxic response to DSBs was P53/TP53-dependent, such that the efficiency of precise genome engineering in hPSCs with a wild-type P53 gene was severely reduced. Our results indicate that Cas9 toxicity creates an obstacle to the high-throughput use of CRISPR/Cas9 for genome engineering and screening in hPSCs. Moreover, as hPSCs can acquire P53 mutations 14 , cell replacement therapies using CRISPR/Cas9-enginereed hPSCs should proceed with caution, and such engineered hPSCs should be monitored for P53 function.

  14. CRISPR/Cas9 delivery with one single adenoviral vector devoid of all viral genes.

    Science.gov (United States)

    Ehrke-Schulz, Eric; Schiwon, Maren; Leitner, Theo; Dávid, Stephan; Bergmann, Thorsten; Liu, Jing; Ehrhardt, Anja

    2017-12-07

    The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 system revolutionized the field of gene editing but viral delivery of the CRISPR/Cas9 system has not been fully explored. Here we adapted clinically relevant high-capacity adenoviral vectors (HCAdV) devoid of all viral genes for the delivery of the CRISPR/Cas9 machinery using a single viral vector. We present a platform enabling fast transfer of the Cas9 gene and gRNA expression units into the HCAdV genome including the option to choose between constitutive or inducible Cas9 expression and gRNA multiplexing. Efficacy and versatility of this pipeline was exemplified by producing different CRISPR/Cas9-HCAdV targeting the human papillomavirus (HPV) 18 oncogene E6, the dystrophin gene causing Duchenne muscular dystrophy (DMD) and the HIV co-receptor C-C chemokine receptor type 5 (CCR5). All CRISPR/Cas9-HCAdV proved to be efficient to deliver the respective CRISPR/Cas9 expression units and to introduce the desired DNA double strand breaks at their intended target sites in immortalized and primary cells.

  15. Single step production of Cas9 mRNA for zygote injection.

    Science.gov (United States)

    Redel, Bethany K; Beaton, Benjamin P; Spate, Lee D; Benne, Joshua A; Murphy, Stephanie L; O'Gorman, Chad W; Spate, Anna M; Prather, Randall S; Wells, Kevin D

    2018-03-01

    Production of Cas9 mRNA in vitro typically requires the addition of a 5´ cap and 3´ polyadenylation. A plasmid was constructed that harbored the T7 promoter followed by the EMCV IRES and a Cas9 coding region. We hypothesized that the use of the metastasis associated lung adenocarcinoma transcript 1 (Malat1) triplex structure downstream of an IRES/Cas9 expression cassette would make polyadenylation of in vitro produced mRNA unnecessary. A sequence from the mMalat1 gene was cloned downstream of the IRES/Cas9 cassette described above. An mRNA concentration curve was constructed with either commercially available Cas9 mRNA or the IRES/ Cas9/triplex, by injection into porcine zygotes. Blastocysts were genotyped to determine if differences existed in the percent of embryos modified. The concentration curve identified differences due to concentration and RNA type injected. Single step production of Cas9 mRNA provides an alternative source of Cas9 for use in zygote injections.

  16. Promoting Cas9 degradation reduces mosaic mutations in non-human primate embryos

    Science.gov (United States)

    Tu, Zhuchi; Yang, Weili; Yan, Sen; Yin, An; Gao, Jinquan; Liu, Xudong; Zheng, Yinghui; Zheng, Jiezhao; Li, Zhujun; Yang, Su; Li, Shihua; Guo, Xiangyu; Li, Xiao-Jiang

    2017-01-01

    CRISPR-Cas9 is a powerful new tool for genome editing, but this technique creates mosaic mutations that affect the efficiency and precision of its ability to edit the genome. Reducing mosaic mutations is particularly important for gene therapy and precision genome editing. Although the mechanisms underlying the CRSIPR/Cas9-mediated mosaic mutations remain elusive, the prolonged expression and activity of Cas9 in embryos could contribute to mosaicism in DNA mutations. Here we report that tagging Cas9 with ubiquitin-proteasomal degradation signals can facilitate the degradation of Cas9 in non-human primate embryos. Using embryo-splitting approach, we found that shortening the half-life of Cas9 in fertilized zygotes reduces mosaic mutations and increases its ability to modify genomes in non-human primate embryos. Also, injection of modified Cas9 in one-cell embryos leads to live monkeys with the targeted gene modifications. Our findings suggest that modifying Cas9 activity can be an effective strategy to enhance precision genome editing. PMID:28155910

  17. Mutagenesis of FAD2 genes in peanut with CRISPR/Cas9

    Science.gov (United States)

    The CRISPR/Cas9 system is known for its precise and efficient gene-editing of a targeted region in a variety of organisms including plants. We targeted FAD2 gene region to perform CRISPR/Cas9 gene-editing in peanut. The FAD2 gene encodes fatty acid desaturase which catalyzes the conversion of oleic ...

  18. CRISPR/Cas systems: new players in gene regulation and bacterial physiology

    Directory of Open Access Journals (Sweden)

    David eWeiss

    2014-04-01

    Full Text Available CRISPR-Cas systems are bacterial defenses against foreign nucleic acids derived from bacteriophages, plasmids or other sources. These systems are targeted in an RNA-dependent, sequence-specific manner, and are also adaptive, providing protection against previously encountered foreign elements. In addition to their canonical function in defense against foreign nucleic acid, their roles in various aspects of bacterial physiology are now being uncovered. We recently revealed a role for a Cas9-based Type II CRISPR-Cas system in the control of endogenous gene expression, a novel form of prokaryotic gene regulation. Cas9 functions in association with two small RNAs to target and alter the stability of an endogenous transcript encoding a bacterial lipoprotein (BLP. Since BLPs are recognized by the host innate immune protein Toll-like Receptor 2 (TLR2, CRISPR-Cas-mediated repression of BLP expression facilitates evasion of TLR2 by the intracellular bacterial pathogen Francisella novicida, and is essential for its virulence. Here we describe the Cas9 regulatory system in detail, as well as data on its role in controlling virulence traits of Neisseria meningitidis and Campylobacter jejuni. We also discuss potential roles of CRISPR-Cas systems in the response to envelope stress and other aspects of bacterial physiology. Since ~45% of bacteria and ~83% of Archaea encode these machineries, the newly appreciated regulatory functions of CRISPR-Cas systems are likely to play broad roles in controlling the pathogenesis and physiology of diverse prokaryotes.

  19. Efficient fdCas9 Synthetic Endonuclease with Improved Specificity for Precise Genome Engineering

    KAUST Repository

    Aouida, Mustapha

    2015-07-30

    The Cas9 endonuclease is used for genome editing applications in diverse eukaryotic species. A high frequency of off-target activity has been reported in many cell types, limiting its applications to genome engineering, especially in genomic medicine. Here, we generated a synthetic chimeric protein between the catalytic domain of the FokI endonuclease and the catalytically inactive Cas9 protein (fdCas9). A pair of guide RNAs (gRNAs) that bind to sense and antisense strands with a defined spacer sequence range can be used to form a catalytically active dimeric fdCas9 protein and generate double-strand breaks (DSBs) within the spacer sequence. Our data demonstrate an improved catalytic activity of the fdCas9 endonuclease, with a spacer range of 15–39 nucleotides, on surrogate reporters and genomic targets. Furthermore, we observed no detectable fdCas9 activity at known Cas9 off-target sites. Taken together, our data suggest that the fdCas9 endonuclease variant is a superior platform for genome editing applications in eukaryotic systems including mammalian cells.

  20. Using local chromatin structure to improve CRISPR/Cas9 efficiency in zebrafish.

    Science.gov (United States)

    Chen, Yunru; Zeng, Shiyang; Hu, Ruikun; Wang, Xiangxiu; Huang, Weilai; Liu, Jiangfang; Wang, Luying; Liu, Guifen; Cao, Ying; Zhang, Yong

    2017-01-01

    Although the CRISPR/Cas9 has been successfully applied in zebrafish, considerable variations in efficiency have been observed for different gRNAs. The workload and cost of zebrafish mutant screening is largely dependent on the mutation rate of injected embryos; therefore, selecting more effective gRNAs is especially important for zebrafish mutant construction. Besides the sequence features, local chromatin structures may have effects on CRISPR/Cas9 efficiency, which remain largely unexplored. In the only related study in zebrafish, nucleosome organization was not found to have an effect on CRISPR/Cas9 efficiency, which is inconsistent with recent studies in vitro and in mammalian cell lines. To understand the effects of local chromatin structure on CRISPR/Cas9 efficiency in zebrafish, we first determined that CRISPR/Cas9 introduced genome editing mainly before the dome stage. Based on this observation, we reanalyzed our published nucleosome organization profiles and generated chromatin accessibility profiles in the 256-cell and dome stages using ATAC-seq technology. Our study demonstrated that chromatin accessibility showed positive correlation with CRISPR/Cas9 efficiency, but we did not observe a clear correlation between nucleosome organization and CRISPR/Cas9 efficiency. We constructed an online database for zebrafish gRNA selection based on local chromatin structure features that could prove beneficial to zebrafish homozygous mutant construction via CRISPR/Cas9.

  1. Engineering Plants for Geminivirus Resistance with CRISPR/Cas9 System

    KAUST Repository

    Zaidi, Syed Shan-e-Ali; Mansoor, Shahid; Ali, Zahir; Tashkandi, Manal; Mahfouz, Magdy M.

    2016-01-01

    The CRISPR/Cas9 system is an efficient genome-editing platform for diverse eukaryotic species, including plants. Recent work harnessed CRISPR/Cas9 technology to engineer resistance to geminiviruses. Here, we discuss opportunities, emerging developments, and potential pitfalls for using this technology to engineer resistance against single and multiple geminivirus infections in plants.

  2. Comparison of CRISPR/Cas9 expression constructs for efficient targeted mutagenesis in rice.

    Science.gov (United States)

    Mikami, Masafumi; Toki, Seiichi; Endo, Masaki

    2015-08-01

    The CRISPR/Cas9 system is an efficient tool used for genome editing in a variety of organisms. Despite several recent reports of successful targeted mutagenesis using the CRISPR/Cas9 system in plants, in each case the target gene of interest, the Cas9 expression system and guide-RNA (gRNA) used, and the tissues used for transformation and subsequent mutagenesis differed, hence the reported frequencies of targeted mutagenesis cannot be compared directly. Here, we evaluated mutation frequency in rice using different Cas9 and/or gRNA expression cassettes under standardized experimental conditions. We introduced Cas9 and gRNA expression cassettes separately or sequentially into rice calli, and assessed the frequency of mutagenesis at the same endogenous targeted sequences. Mutation frequencies differed significantly depending on the Cas9 expression cassette used. In addition, a gRNA driven by the OsU6 promoter was superior to one driven by the OsU3 promoter. Using an all-in-one expression vector harboring the best combined Cas9/gRNA expression cassette resulted in a much improved frequency of targeted mutagenesis in rice calli, and bi-allelic mutant plants were produced in the T0 generation. The approach presented here could be adapted to optimize the construction of Cas9/gRNA cassettes for genome editing in a variety of plants.

  3. Repetitive DNA Reeling by the Cascade-Cas3 Complex in Nucleotide Unwinding Steps

    NARCIS (Netherlands)

    Loeff, Luuk; Brouns, Stan J.J.; Joo, Chirlmin

    2018-01-01

    CRISPR-Cas provides RNA-guided adaptive immunity against invading genetic elements. Interference in type I systems relies on the RNA-guided Cascade complex for target DNA recognition and the Cas3 helicase/nuclease protein for target degradation. Even though the biochemistry of CRISPR interference

  4. CAS Panel Proposes Priorities for Earth Science in Next Two Decades

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    @@ CAS member Zhao Zhongxian, director of Working Committee on Consultation and Evaluation of the CAS Academic Divisions (CASAD),has announced that the Academic Division of Earth Sciences has drafted a consultative report on planning and strategic studies of the mid- and long-term development for earth sciences in China.

  5. In vivo genome editing via CRISPR/Cas9 mediated homology-independent targeted integration

    KAUST Repository

    Suzuki, Keiichiro; Tsunekawa, Yuji; Herná ndez-Bení tez, Reyna; Wu, Jun; Zhu, Jie; Kim, Euiseok J.; Hatanaka, Fumiyuki; Yamamoto, Mako; Araoka, Toshikazu; Li, Zhe; Kurita, Masakazu; Hishida, Tomoaki; Li, Mo; Aizawa, Emi; Guo, Shicheng; Chen, Song; Goebl, April; Soligalla, Rupa Devi; Qu, Jing; Jiang, Tingshuai; Fu, Xin; Jafari, Maryam; Esteban, Concepcion Rodriguez; Berggren, W. Travis; Lajara, Jeronimo; Nuñ ez-Delicado, Estrella; Guillen, Pedro; Campistol, Josep M.; Matsuzaki, Fumio; Liu, Guang-Hui; Magistretti, Pierre J.; Zhang, Kun; Callaway, Edward M.; Zhang, Kang; Belmonte, Juan Carlos Izpisua

    2016-01-01

    regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9)3, 4 technology, here we devise a homology-independent targeted integration (HITI) strategy, which allows for robust DNA knock-in in both dividing and non-dividing cells in vitro and, more

  6. Diverse evolutionary roots and mechanistic variations of the CRISPR-Cas systems

    NARCIS (Netherlands)

    Mohanraju, Prarthana; Makarova, Kira S.; Zetsche, Bernd; Zhang, Feng; Koonin, Eugene V.; Oost, van der John

    2016-01-01

    Adaptive immunity had been long thought of as an exclusive feature of animals. However, the discovery of the CRISPR-Cas defense system, present in almost half of prokaryotic genomes, proves otherwise. Because of the everlasting parasite-host arms race, CRISPR-Cas has rapidly evolved through

  7. Structure of a CRISPR-associated protein Cas2 from Desulfovibrio vulgaris

    Energy Technology Data Exchange (ETDEWEB)

    Samai, Poulami; Smith, Paul; Shuman, Stewart [Molecular Biology Program, Sloan-Kettering Institute for Cancer Research (United States)

    2010-12-01

    A 1.35 Å resolution crystal structure of Cas2 from the bacterium Desulfovibrio vulgaris (DvuCas2) is reported. CRISPRs (clustered regularly interspaced short palindromic repeats) provide bacteria and archaea with RNA-guided acquired immunity to invasive DNAs. CRISPR-associated (Cas) proteins carry out the immune effector functions. Cas2 is a universal component of the CRISPR system. Here, a 1.35 Å resolution crystal structure of Cas2 from the bacterium Desulfovibrio vulgaris (DvuCas2) is reported. DvuCas2 is a homodimer, with each protomer consisting of an N-terminal βαββαβ ferredoxin fold (amino acids 1–78) to which is appended a C-terminal segment (amino acids 79–102) that includes a short 3{sub 10}-helix and a fifth β-strand. The β5 strands align with the β4 strands of the opposite protomers, resulting in two five-stranded antiparallel β-sheets that form a sandwich at the dimer interface. The DvuCas2 dimer is stabilized by a distinctive network of hydrophilic cross-protomer side-chain interactions.

  8. Optimization of genome engineering approaches with the CRISPR/Cas9 system

    DEFF Research Database (Denmark)

    Li, Kai; Wang, Gang; Andersen, Troels

    2014-01-01

    Designer nucleases such as TALENS and Cas9 have opened new opportunities to scarlessly edit the mammalian genome. Here we explored several parameters that influence Cas9-mediated scarless genome editing efficiency in murine embryonic stem cells. Optimization of transfection conditions and enrichi...

  9. Antiviral Goes Viral : Harnessing CRISPR/Cas9 to Combat Viruses in Humans

    NARCIS (Netherlands)

    Soppe, Jasper Adriaan; Lebbink, Robert Jan

    2017-01-01

    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

  10. Engineering Plants for Geminivirus Resistance with CRISPR/Cas9 System

    KAUST Repository

    Zaidi, Syed Shan-e-Ali

    2016-02-14

    The CRISPR/Cas9 system is an efficient genome-editing platform for diverse eukaryotic species, including plants. Recent work harnessed CRISPR/Cas9 technology to engineer resistance to geminiviruses. Here, we discuss opportunities, emerging developments, and potential pitfalls for using this technology to engineer resistance against single and multiple geminivirus infections in plants.

  11. Structure of a CRISPR-associated protein Cas2 from Desulfovibrio vulgaris

    International Nuclear Information System (INIS)

    Samai, Poulami; Smith, Paul; Shuman, Stewart

    2010-01-01

    A 1.35 Å resolution crystal structure of Cas2 from the bacterium Desulfovibrio vulgaris (DvuCas2) is reported. CRISPRs (clustered regularly interspaced short palindromic repeats) provide bacteria and archaea with RNA-guided acquired immunity to invasive DNAs. CRISPR-associated (Cas) proteins carry out the immune effector functions. Cas2 is a universal component of the CRISPR system. Here, a 1.35 Å resolution crystal structure of Cas2 from the bacterium Desulfovibrio vulgaris (DvuCas2) is reported. DvuCas2 is a homodimer, with each protomer consisting of an N-terminal βαββαβ ferredoxin fold (amino acids 1–78) to which is appended a C-terminal segment (amino acids 79–102) that includes a short 3 10 -helix and a fifth β-strand. The β5 strands align with the β4 strands of the opposite protomers, resulting in two five-stranded antiparallel β-sheets that form a sandwich at the dimer interface. The DvuCas2 dimer is stabilized by a distinctive network of hydrophilic cross-protomer side-chain interactions

  12. Structural Plasticity of PAM Recognition by Engineered Variants of the RNA-Guided Endonuclease Cas9.

    Science.gov (United States)

    Anders, Carolin; Bargsten, Katja; Jinek, Martin

    2016-03-17

    The RNA-guided endonuclease Cas9 from Streptococcus pyogenes (SpCas9) forms the core of a powerful genome editing technology. DNA cleavage by SpCas9 is dependent on the presence of a 5'-NGG-3' protospacer adjacent motif (PAM) in the target DNA, restricting the choice of targetable sequences. To address this limitation, artificial SpCas9 variants with altered PAM specificities have recently been developed. Here we report crystal structures of the VQR, EQR, and VRER SpCas9 variants bound to target DNAs containing their preferred PAM sequences. The structures reveal that the non-canonical PAMs are recognized by an induced fit mechanism. Besides mediating sequence-specific base recognition, the amino acid substitutions introduced in the SpCas9 variants facilitate conformational remodeling of the PAM region of the bound DNA. Guided by the structural data, we engineered a SpCas9 variant that specifically recognizes NAAG PAMs. Taken together, these studies inform further development of Cas9-based genome editing tools. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. 78 FR 40665 - Cost Accounting Standards: CAS 413 Pension Adjustments for Extraordinary Events

    Science.gov (United States)

    2013-07-08

    ... Accounting Standards: CAS 413 Pension Adjustments for Extraordinary Events AGENCY: Cost Accounting Standards...: The Office of Federal Procurement Policy (OFPP), Cost Accounting Standards (CAS) Board, is conducting... Extraordinary Events. This is the first step in a four- step process that may result in a final rule. As part of...

  14. Auditing the Functional Part of the CAS Software

    Directory of Open Access Journals (Sweden)

    Adamyk Oksana V.

    2017-11-01

    Full Text Available The article is aimed at determining the order and methodology of auditing the functional component of the software for an computer accounting system (CAS. It has been found that software auditing should be performed separately for each of its components. The components of the functional part of the CAS software are the database management system (DBMS and the application software supporting the accountance automation. For auditing of the first component part are used such techniques as general evaluation, subject check of the embedded algorithms of information processing. Auditing the client software algorithms is carried out by means of the control data method, which is reduced to such procedures as creation of another database of test data with imaginary objects and its processing by the client program, as well as introduction in a copy of the real database of imaginary objects (employees, creditors, material values and the formation of reporting. Not only the current methods of calculation or evaluation of accounting objects, but all of the software, are subject to mandatory verification. This will avoid errors if the enterprise accounting policy changes.

  15. The linear collider alignment and survey (LiCAS) project

    International Nuclear Information System (INIS)

    Bingham, Richard; Botcherby, Edward; Coe, Paul; Grzelak, Grzegorz; Mitra, Ankush; Reichold, Armin; Prenting, Johannes

    2003-01-01

    For the next generation of Linear Colliders (LC) the precision alignment of accelerator components will be critical. The DESY applied geodesy group has developed the concept of an automated 'survey train'. The train runs along the accelerator wall measuring the 3D position of a set of equispaced reference markers. This reference structure is then used to align the accelerator components. The LiCAS group is developing a measurement system for the survey train. It will use a combination of Laser Straightness Monitors (SM) and Frequency Scanning Interferometry (FSI). FSI is an interferometric length measurement technique originally developed for the online alignment of the ATLAS Inner Detector. This novel combination of optical techniques is expected to overcome the limitations of traditional open air survey. The authors describe the LiCAS project, the measurement systems and their integration into the survey train. The technical parameters and constraints will be mentioned. There will also be brief discussion of the second phase of the project to allow on-line monitoring of the LC alignment. (author)

  16. CAS-NETL-PNNL CEP Program Final Report

    Energy Technology Data Exchange (ETDEWEB)

    King, David L.; Spies, Kurt A.; Rainbolt, James E.; Zhang, Keling

    2014-03-31

    This collaborative joint research project is in the area of advanced gasification and conversion, within the CAS-NETL-PNNL Memorandum of Understanding. The goal is the development and testing of an integrated warm syngas cleanup process. This effort is focused on an advanced, integrated system for capture and removal of alkali, sulfur, PH3, AsH3, chloride, and CO2, leading to a future process demonstration at a CAS gasification facility. Syngas produced by gasification can be used for production of fuels (Fischer-Tropsch, SNG, mixed alcohols), chemicals (MeOH, NH3), and hydrogen for fuel cells and IGCC. To employ this syngas, especially for synthesis reactions, contained impurities must be removed to sub-ppmv levels [1]. Commercially available approaches to remove contaminant species suffer from inefficiencies, employing solvents at ambient or lower temperature along with backup sacrificial sorbents, whereas syngas utilization occurs at higher temperatures. The efficiency and economics syngas utilization can be significantly improved if all the contaminants and CO2 are removed at temperatures higher than the chemical synthesis reaction temperatures (> 250 °C) [2].

  17. 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.

  18. Center for Deployment Psychology

    Data.gov (United States)

    Federal Laboratory Consortium — The Center for Deployment Psychology was developed to promote the education of psychologists and other behavioral health specialists about issues pertaining to the...

  19. Psychology in Japan.

    Science.gov (United States)

    Imada, Hiroshi; Tanaka-Matsumi, Junko

    2016-06-01

    The purpose of this article is to provide information about Japan and its psychology in advance of the 31st International Congress of Psychology (ICP), to be held in Yokohama, Japan, in 2016. The article begins with the introduction of the Japanese Psychological Association (JPA), the hosting organization of the ICP 2016, and the Japanese Union of Psychological Associations consisting of 51 associations/societies, of which the JPA is a member. This is followed by a brief description of a history of psychology of Japan, with emphasis on the variation in our approach to psychology in three different periods, that is, the pre- and post-Pacific War periods, and the post-1960 period. Next, the international contributions of Japanese psychology/psychologists are discussed from the point of view of their visibility. Education and training in psychology in Japanese universities is discussed with a final positive remark about the long-awaited enactment of the Accredited Psychologist Law in September, 2015. © 2016 International Union of Psychological Science.

  20. Nonlinear dynamics in psychology

    Directory of Open Access Journals (Sweden)

    Stephen J. Guastello

    2001-01-01

    Full Text Available This article provides a survey of the applications of nonlinear dynamical systems theory to substantive problems encountered in the full scope of psychological science. Applications are organized into three topical areas – cognitive science, social and organizational psychology, and personality and clinical psychology. Both theoretical and empirical studies are considered with an emphasis on works that capture the broadest scope of issues that are of substantive interest to psychological theory. A budding literature on the implications of NDS principles in professional practice is reported also.