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Sample records for outsmarting flu viruses

  1. Toward Design of a Universal Flu Vaccine

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Toward Design of a Universal Flu Vaccine Print Worldwide, influenza causes substantial deaths and yearly economic burdens, but the highly changeable nature of the flu virus ...

  2. Toward Design of a Universal Flu Vaccine

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Toward Design of a Universal Flu Vaccine Print Worldwide, influenza causes substantial deaths and yearly economic burdens, but the highly changeable nature of the flu virus...

  3. Toward Design of a Universal Flu Vaccine

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Toward Design of a Universal Flu Vaccine Toward Design of a Universal Flu Vaccine Print Wednesday, 30 January 2013 00:00 Worldwide, influenza causes substantial deaths and yearly economic burdens, but the highly changeable nature of the flu virus complicates the production of an effective vaccine. The Centers for Disease Control and Prevention (CDC) estimates that the effectiveness of this year's flu vaccine is about 62%. For comparison, this number for childhood vaccines is routinely well over

  4. Forecasting Flu

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Forecasting Flu March 6, 2016 Forecasting Flu What if we could forecast infectious diseases the same way we forecast the weather, and predict how diseases like Dengue, Typhus or Zika were going to spread? Using real-time data from Wikipedia and social media, Sara del Valle and her team from Los Alamos National Laboratory have developed a global disease-forecasting system that will improve the way we respond to epidemics. Using this model, individuals and public health officials can monitor

  5. Toward Design of a Universal Flu Vaccine

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Toward Design of a Universal Flu Vaccine Print Worldwide, influenza causes substantial deaths and yearly economic burdens, but the highly changeable nature of the flu virus complicates the production of an effective vaccine. The Centers for Disease Control and Prevention (CDC) estimates that the effectiveness of this year's flu vaccine is about 62%. For comparison, this number for childhood vaccines is routinely well over 90%. One factor in determining the vaccine's effectiveness is how closely

  6. Toward Design of a Universal Flu Vaccine

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Toward Design of a Universal Flu Vaccine Print Worldwide, influenza causes substantial deaths and yearly economic burdens, but the highly changeable nature of the flu virus complicates the production of an effective vaccine. The Centers for Disease Control and Prevention (CDC) estimates that the effectiveness of this year's flu vaccine is about 62%. For comparison, this number for childhood vaccines is routinely well over 90%. One factor in determining the vaccine's effectiveness is how closely

  7. Toward Design of a Universal Flu Vaccine

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Toward Design of a Universal Flu Vaccine Print Worldwide, influenza causes substantial deaths and yearly economic burdens, but the highly changeable nature of the flu virus complicates the production of an effective vaccine. The Centers for Disease Control and Prevention (CDC) estimates that the effectiveness of this year's flu vaccine is about 62%. For comparison, this number for childhood vaccines is routinely well over 90%. One factor in determining the vaccine's effectiveness is how closely

  8. Structure and Receptor Specificity of an Avian Flu Antigen

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    and Receptor Specificity of an Avian Flu Antigen Print To date, the H5N1 avian influenza viruses, which are currently circulating in domestic and wild birds on three...

  9. Structure and Receptor Specificity of an Avian Flu Antigen

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Structure and Receptor Specificity of an Avian Flu Antigen Print To date, the H5N1 avian influenza viruses, which are currently circulating in domestic and wild birds on three...

  10. Structure and Receptor Specificity of an Avian Flu Antigen

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    and Receptor Specificity of an Avian Flu Antigen Print To date, the H5N1 avian influenza viruses, which are currently circulating in domestic and wild birds on three continents,...

  11. Structure and Receptor Specificity of an Avian Flu Antigen

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Structure and Receptor Specificity of an Avian Flu Antigen Structure and Receptor Specificity of an Avian Flu Antigen Print Wednesday, 25 July 2007 00:00 To date, the H5N1 avian influenza viruses, which are currently circulating in domestic and wild birds on three continents, have only a limited ability to infect humans. However, with continued outbreaks of the virus in poultry and wild birds, the potential for the emergence of a human-adapted H5 virus, either by reassortment (the mixing of

  12. The forecast calls for flu

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Laboratory found a way to forecast the flu season and even next week's sickness trends. ... Laboratory found a way to forecast the flu season and even next week's sickness trends. ...

  13. Structure and Receptor Specificity of an Avian Flu Antigen

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Structure and Receptor Specificity of an Avian Flu Antigen Print To date, the H5N1 avian influenza viruses, which are currently circulating in domestic and wild birds on three continents, have only a limited ability to infect humans. However, with continued outbreaks of the virus in poultry and wild birds, the potential for the emergence of a human-adapted H5 virus, either by reassortment (the mixing of genetic material from similar viruses) or mutation, is seen as a major threat to public

  14. Structure and Receptor Specificity of an Avian Flu Antigen

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Structure and Receptor Specificity of an Avian Flu Antigen Print To date, the H5N1 avian influenza viruses, which are currently circulating in domestic and wild birds on three continents, have only a limited ability to infect humans. However, with continued outbreaks of the virus in poultry and wild birds, the potential for the emergence of a human-adapted H5 virus, either by reassortment (the mixing of genetic material from similar viruses) or mutation, is seen as a major threat to public

  15. Structure and Receptor Specificity of an Avian Flu Antigen

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Structure and Receptor Specificity of an Avian Flu Antigen Print To date, the H5N1 avian influenza viruses, which are currently circulating in domestic and wild birds on three continents, have only a limited ability to infect humans. However, with continued outbreaks of the virus in poultry and wild birds, the potential for the emergence of a human-adapted H5 virus, either by reassortment (the mixing of genetic material from similar viruses) or mutation, is seen as a major threat to public

  16. Structure and Receptor Specificity of an Avian Flu Antigen

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    and Receptor Specificity of an Avian Flu Antigen Print To date, the H5N1 avian influenza viruses, which are currently circulating in domestic and wild birds on three continents, have only a limited ability to infect humans. However, with continued outbreaks of the virus in poultry and wild birds, the potential for the emergence of a human-adapted H5 virus, either by reassortment (the mixing of genetic material from similar viruses) or mutation, is seen as a major threat to public health

  17. Toward Design of a Universal Flu Vaccine

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Toward Design of a Universal Flu Vaccine Toward Design of a Universal Flu Vaccine Print Wednesday, 30 January 2013 00:00 Worldwide, influenza causes substantial deaths and yearly ...

  18. Better predicting flu outbreaks with Wikipedia

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Better predicting flu outbreaks with Wikipedia Better predicting flu outbreaks with Wikipedia Scientists at Los Alamos National Laboratory have the ability to forecast the upcoming flu season and other infectious diseases by analyzing views of Wikipedia articles May 14, 2015 From Left: Kyle Hickmann, Nick Generous, Geoffrey Fairchild, James Hyman (back), Alina Deshpande and Sara Del Valle (front). From Left: Kyle Hickmann, Nick Generous, Geoffrey Fairchild, Reid Priedhorsky (back), Alina

  19. Picture of the Week: Forecasting Flu

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    3 Forecasting Flu What if we could forecast infectious diseases the same way we forecast the weather, and predict how diseases like Dengue, Typhus or Zika were going to spread? March 6, 2016 flu epidemics modellled using social media Watch the video on YouTube. Forecasting Flu What if we could forecast infectious diseases the same way we forecast the weather, and predict how diseases like Dengue, Typhus or Zika were going to spread? Using real-time data from Wikipedia and social media, Sara del

  20. Our view: Vaccinate now, prevent flu later

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    scientists can say this because of the model they have constructed. December 24, 2015 Man sneezing Model suggests still time to get your flu shot and be protected. "There's no...

  1. February most likely month for flu season to peak

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    February most likely month for flu season to peak February most likely month for flu season to peak The Los Alamos team's model is an ongoing research project that forecasts the current flu season probabilistically, similar to best-practice forecasts of weather, presidential elections, and sporting events. December 20, 2015 The Los Alamos team's model is an ongoing research project that forecasts the current flu season probabilistically, similar to best-practice forecasts of weather,

  2. Battling bird flu by the numbers

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Battling bird flu by the numbers Battling bird flu by the numbers Lab theorists have developed a mathematical tool that could help health experts and crisis managers determine in real time whether an emerging infectious disease such as avian influenza H5N1 is poised to spread globally. May 27, 2008 Los Alamos National Laboratory sits on top of a once-remote mesa in northern New Mexico with the Jemez mountains as a backdrop to research and innovation covering multi-disciplines from bioscience,

  3. Occ. Med. Offers Staff Flu Vaccines by Appointment | Jefferson...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Occ. Med. Offers Staff Flu Vaccines by Appointment Occupational Medicine is now accepting appointments from Jefferson Lab staff for Influenza vaccinations. If you would like to be...

  4. Point-of-Care Flu Diagnosis | GE Global Research

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    device that can diagnose the flu and other infectious diseases such as malaria, E. coli and salmonella at the point of care. In addition to making an accurate diagnosis,...

  5. Flu shots available beginning Oct. 5 | The Ames Laboratory

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    battle the flu Wash hands regularly with soap and water, use hand sanitizer Sneeze and cough into a sleeve or tissue Stay home when sick Regularly sanitize work surfaces and...

  6. Fast pandemic detection tool ready to fight flu

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Fast pandemic detection tool ready to fight flu Fast pandemic detection tool ready to fight flu Researchers are developing new tools for rapidly characterizing biological pathogens that could give rise to potentially deadly pandemics such as Influenza A (H1N1). June 9, 2009 Los Alamos National Laboratory sits on top of a once-remote mesa in northern New Mexico with the Jemez mountains as a backdrop to research and innovation covering multi-disciplines from bioscience, sustainable energy sources,

  7. Toward Design of a Universal Flu Vaccine

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    large structural differences from CR9114, indicating that, while they bind to a similar region on various viruses, they employ different strategies for neutralizing those...

  8. Toward Design of a Universal Flu Vaccine

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    which antibodies can be raised. Influenza A viruses are classified into subtypes, such as H1N1 or H3N2, based on antibody responses to HA and NA. Human antibodies are large...

  9. City of Chicago won't sweat the flu with Argonne's help | Argonne...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    on their toes." This particular exercise followed the spread of an imaginary flu from Egypt. By the time the flu "arrived" in Chicago, more than 15,000 cases had been reported...

  10. Structure and Receptor Specificity of an Avian Flu Antigen

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    combined effects could allow the Viet04 virus to escape entrapment by mucins in the lungs and increase binding to susceptible human epithelial cells. These mutations therefore...

  11. Structural Basis of Preexisting Immunity to the 2009 H1N1 Pandemic Influenza Virus

    SciTech Connect (OSTI)

    Xu, Rui; Ekiert, Damian C.; Krause, Jens C.; Hai, Rong; Crowe, Jr., James E.; Wilson, Ian A.

    2010-05-25

    The 2009 H1N1 swine flu is the first influenza pandemic in decades. The crystal structure of the hemagglutinin from the A/California/04/2009 H1N1 virus shows that its antigenic structure, particularly within the Sa antigenic site, is extremely similar to those of human H1N1 viruses circulating early in the 20th century. The cocrystal structure of the 1918 hemagglutinin with 2D1, an antibody from a survivor of the 1918 Spanish flu that neutralizes both 1918 and 2009 H1N1 viruses, reveals an epitope that is conserved in both pandemic viruses. Thus, antigenic similarity between the 2009 and 1918-like viruses provides an explanation for the age-related immunity to the current influenza pandemic.

  12. Science Summary

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    that can take out an unprecedented number of different types of flu viruses, including H5N1 'bird flu' and the 1918 H1N1 'Spanish flu', which killed millions around the world...

  13. Generating electricity from viruses

    ScienceCinema (OSTI)

    Lee, Seung-Wuk

    2014-06-23

    Berkeley Lab's Seung-Wuk Lee discusses "Generating electricity from viruses" in this Oct. 28, 2013 talk, which is part of a Science at the Theater event entitled Eight Big Ideas.

  14. Generating electricity from viruses

    SciTech Connect (OSTI)

    Lee, Seung-Wuk

    2013-10-31

    Berkeley Lab's Seung-Wuk Lee discusses "Generating electricity from viruses" in this Oct. 28, 2013 talk, which is part of a Science at the Theater event entitled Eight Big Ideas.

  15. Production of virus resistant plants

    DOE Patents [OSTI]

    Dougherty, William G. (Philomath, OR); Lindbo, John A. (Kent, WA)

    1996-01-01

    A method of suppressing virus gene expression in plants using untranslatable plus sense RNA is disclosed. The method is useful for the production of plants that are resistant to virus infection.

  16. Production of virus resistant plants

    DOE Patents [OSTI]

    Dougherty, W.G.; Lindbo, J.A.

    1996-12-10

    A method of suppressing virus gene expression in plants using untranslatable plus sense RNA is disclosed. The method is useful for the production of plants that are resistant to virus infection. 9 figs.

  17. From Shakespeare to Viruses

    ScienceCinema (OSTI)

    Kim, Sung-Hou

    2013-05-29

    Berkeley Lab scientists have created a unique new tool for analyzing and comparing long sets of data, be it the genomes of mammals or viruses, or the works of Shakespeare. The results of the Shakespeare analysis surprised scholars with their accuracy.

  18. From Shakespeare to Viruses

    ScienceCinema (OSTI)

    Sung-Hou Kim

    2010-01-08

    Berkeley Lab scientists have created a unique new tool for analyzing and comparing long sets of data, be it the genomes of mammals or viruses, or the works of Shakespeare. The results of the Shakespeare analysis surprised scholars with their accuracy

  19. Computer virus information update CIAC-2301

    SciTech Connect (OSTI)

    Orvis, W.J.

    1994-01-15

    While CIAC periodically issues bulletins about specific computer viruses, these bulletins do not cover all the computer viruses that affect desktop computers. The purpose of this document is to identify most of the known viruses for the MS-DOS and Macintosh platforms and give an overview of the effects of each virus. The authors also include information on some windows, Atari, and Amiga viruses. This document is revised periodically as new virus information becomes available. This document replaces all earlier versions of the CIAC Computer virus Information Update. The date on the front cover indicates date on which the information in this document was extracted from CIAC`s Virus database.

  20. Stanford Synchrotron Radiation Lightsource

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    the design principles of natural functional sites. The team targeted a surface on the influenza hemagglutinin protein that enables flu viruses to attach to and invade cells lining...

  1. Immunogenic compositions comprising human immunodeficiency virus...

    Office of Scientific and Technical Information (OSTI)

    Patent: Immunogenic compositions comprising human immunodeficiency virus (HIV) mosaic Nef proteins Citation Details In-Document Search Title: Immunogenic compositions comprising...

  2. Recombinant herpes simplex virus useful for treating neoplastic disease

    DOE Patents [OSTI]

    Whitley, Richard J.; Roizman, Bernard

    2010-06-29

    Recombinant herpes simplex viruses comprising DNA encoding cytokines and methods for treating neoplastic diseases using the inventive recombinant viruses are disclosed.

  3. Human immunodeficiency virus type 1 clade M mosaic gag polypeptides...

    Office of Scientific and Technical Information (OSTI)

    Patent: Human immunodeficiency virus type 1 clade M mosaic gag polypeptides Citation Details In-Document Search Title: Human immunodeficiency virus type 1 clade M mosaic gag ...

  4. Structure and Mutagenesis of the Parainfluenza Virus 5Hemagglutinin...

    Office of Scientific and Technical Information (OSTI)

    and Mutagenesis of the Parainfluenza Virus 5 Hemagglutinin-Neuraminidase Stalk Domain ... Title: Structure and Mutagenesis of the Parainfluenza Virus 5 Hemagglutinin-Neuraminidase ...

  5. Structure of the Newcastle disease virus hemagglutinin-neuraminidase...

    Office of Scientific and Technical Information (OSTI)

    virus hemagglutinin-neuraminidase (HN) ectodomain reveals a four-helix bundle stalk Citation Details In-Document Search Title: Structure of the Newcastle disease virus ...

  6. Human immunodeficiency virus type 1 clade M mosaic gag polypeptides...

    Office of Scientific and Technical Information (OSTI)

    Patent: Human immunodeficiency virus type 1 clade M mosaic gag polypeptides Citation Details In-Document Search Title: Human immunodeficiency virus type 1 clade M mosaic gag...

  7. Designer Proteins Target Epstein-Barr-Virus-Associated Cancer

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Designer Proteins Target Epstein-Barr-Virus-Associated Cancer Designer Proteins Target Epstein-Barr-Virus-Associated Cancer Print Wednesday, 03 December 2014 00:00 Immortality is...

  8. Microsoft Word - 1918flu.doc

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    required for influenza infection. One patch, unique to both human and avian H1, H2 and H5 subtypes, is adjacent to the cleavage site, and may be involved in either trimer...

  9. Treatment of tumors with genetically engineered herpes virus

    DOE Patents [OSTI]

    Weichselbaum, Ralph R; Roizman, Bernard; Whitley, Richard J

    2012-11-27

    Disclosed are methods for treating cancer by administering an effective amount of a modified Herpes simplex virus.

  10. Structure of the Triatoma virus capsid

    SciTech Connect (OSTI)

    Squires, Gaëlle; Pous, Joan; Agirre, Jon; Rozas-Dennis, Gabriela S.; Costabel, Marcelo D.; Marti, Gerardo A.; Navaza, Jorge; Bressanelli, Stéphane; Guérin, Diego M. A.; Rey, Felix A.

    2013-06-01

    The crystallographic structure of TrV shows specific morphological and functional features that clearly distinguish it from the type species of the Cripavirus genus, CrPV. The members of the Dicistroviridae family are non-enveloped positive-sense single-stranded RNA (+ssRNA) viruses pathogenic to beneficial arthropods as well as insect pests of medical importance. Triatoma virus (TrV), a member of this family, infects several species of triatomine insects (popularly named kissing bugs), which are vectors for human trypanosomiasis, more commonly known as Chagas disease. The potential use of dicistroviruses as biological control agents has drawn considerable attention in the past decade, and several viruses of this family have been identified, with their targets covering honey bees, aphids and field crickets, among others. Here, the crystal structure of the TrV capsid at 2.5 Ć resolution is reported, showing that as expected it is very similar to that of Cricket paralysis virus (CrPV). Nevertheless, a number of distinguishing structural features support the introduction of a new genus (Triatovirus; type species TrV) under the Dicistroviridae family. The most striking differences are the absence of icosahedrally ordered VP4 within the infectious particle and the presence of prominent projections that surround the fivefold axis. Furthermore, the structure identifies a second putative autoproteolytic DDF motif in protein VP3, in addition to the conserved one in VP1 which is believed to be responsible for VP0 cleavage during capsid maturation. The potential meaning of these new findings is discussed.

  11. Serial femtosecond X-ray diffraction of enveloped virus microcrystals

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Lawrence, Robert M.; Conrad, Chelsie E.; Zatsepin, Nadia A.; Grant, Thomas D.; Liu, Haiguang; James, Daniel; Nelson, Garrett; Subramanian, Ganesh; Aquila, Andrew; Hunter, Mark S.; et al

    2015-08-20

    Serial femtosecond crystallography (SFX) using X-ray free-electron lasers has produced high-resolution, room temperature, time-resolved protein structures. We report preliminary SFX of Sindbis virus, an enveloped icosahedral RNA virus with ~700 Å diameter. Microcrystals delivered in viscous agarose medium diffracted to ~40 Å resolution. Small-angle diffuse X-ray scattering overlaid Bragg peaks and analysis suggests this results from molecular transforms of individual particles. Viral proteins undergo structural changes during entry and infection, which could, in principle, be studied with SFX. This is a pertinent step toward determining room temperature structures from virus microcrystals that may enable time-resolved studies of enveloped viruses.

  12. HIV virus spread and evolution studied through computer modeling

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    and the actual, rapid evolution of the virus (phylogenetics) within each patient's body. "We have developed novel ways of estimating epidemics dynamics such as who infected...

  13. Genomics-enabled sensor platform for rapid detection of viruses...

    Office of Scientific and Technical Information (OSTI)

    platforms for preclinical and field testing that utilize the assays developed in goal 1. We generated and characterized suitable primersmore for West Nile Virus RNA detection. ...

  14. Serial femtosecond X-ray diffraction of enveloped virus microcrystals

    SciTech Connect (OSTI)

    Lawrence, Robert M.; Conrad, Chelsie E.; Zatsepin, Nadia A.; Grant, Thomas D.; Liu, Haiguang; James, Daniel; Nelson, Garrett; Subramanian, Ganesh; Aquila, Andrew; Hunter, Mark S.; Liang, Mengning; Boutet, Sébastien; Coe, Jesse; Spence, John C. H.; Weierstall, Uwe; Liu, Wei; Fromme, Petra; Cherezov, Vadim; Hogue, Brenda G.

    2015-08-20

    Serial femtosecond crystallography (SFX) using X-ray free-electron lasers has produced high-resolution, room temperature, time-resolved protein structures. We report preliminary SFX of Sindbis virus, an enveloped icosahedral RNA virus with ~700 Ć diameter. Microcrystals delivered in viscous agarose medium diffracted to ~40 Ć resolution. Small-angle diffuse X-ray scattering overlaid Bragg peaks and analysis suggests this results from molecular transforms of individual particles. Viral proteins undergo structural changes during entry and infection, which could, in principle, be studied with SFX. This is a pertinent step toward determining room temperature structures from virus microcrystals that may enable time-resolved studies of enveloped viruses.

  15. Designer Proteins Target Epstein-Barr-Virus-Associated Cancer

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Designer Proteins Target Epstein-Barr-Virus-Associated Cancer Print Immortality is not a good thing for cells, and in fact, cells will destroy themselves in a process called apoptosis when they are a danger to other cells. For instance, when a cell is infected by a virus it becomes an unwilling factory for the virus, which uses the cell machinery to produce ever more copies of itself. Eventually, if the cell doesn't die, it will spew all those new viruses into the bloodstream. The process of

  16. Designer Proteins Target Epstein-Barr-Virus-Associated Cancer

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Designer Proteins Target Epstein-Barr-Virus-Associated Cancer Print Immortality is not a good thing for cells, and in fact, cells will destroy themselves in a process called apoptosis when they are a danger to other cells. For instance, when a cell is infected by a virus it becomes an unwilling factory for the virus, which uses the cell machinery to produce ever more copies of itself. Eventually, if the cell doesn't die, it will spew all those new viruses into the bloodstream. The process of

  17. Designer Proteins Target Epstein-Barr-Virus-Associated Cancer

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Designer Proteins Target Epstein-Barr-Virus-Associated Cancer Print Immortality is not a good thing for cells, and in fact, cells will destroy themselves in a process called apoptosis when they are a danger to other cells. For instance, when a cell is infected by a virus it becomes an unwilling factory for the virus, which uses the cell machinery to produce ever more copies of itself. Eventually, if the cell doesn't die, it will spew all those new viruses into the bloodstream. The process of

  18. Designer Proteins Target Epstein-Barr-Virus-Associated Cancer

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Designer Proteins Target Epstein-Barr-Virus-Associated Cancer Print Immortality is not a good thing for cells, and in fact, cells will destroy themselves in a process called apoptosis when they are a danger to other cells. For instance, when a cell is infected by a virus it becomes an unwilling factory for the virus, which uses the cell machinery to produce ever more copies of itself. Eventually, if the cell doesn't die, it will spew all those new viruses into the bloodstream. The process of

  19. Designer Proteins Target Epstein-Barr-Virus-Associated Cancer

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Designer Proteins Target Epstein-Barr-Virus-Associated Cancer Designer Proteins Target Epstein-Barr-Virus-Associated Cancer Print Wednesday, 03 December 2014 00:00 Immortality is not a good thing for cells, and in fact, cells will destroy themselves in a process called apoptosis when they are a danger to other cells. For instance, when a cell is infected by a virus it becomes an unwilling factory for the virus, which uses the cell machinery to produce ever more copies of itself. Eventually, if

  20. ALS Capabilities Reveal Multiple Functions of Ebola Virus

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Reveal Multiple Functions of Ebola Virus Print A central dogma of molecular biology is that a protein's sequence dictates its fold, and the fold dictates its function....

  1. Immobilization and One-Dimensional Arrangement of Virus Capsids...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    and One-Dimensional Arrangement of Virus Capsids with Nanoscale Precision Using DNA Origami Authors: Stephanopoulos, N., Liu, M., Tong, G., Li, Z., Liu, Y., Yan, H., and...

  2. Structural Rearrangement in Ebola Virus Protein VP40 Creates...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    lab revealed how the filaments undergo electrostatically driven rearrangements and polymerization to build and bud Ebola virus virions. Atomic models built from their structures...

  3. Genomics-enabled sensor platform for rapid detection of viruses...

    Office of Scientific and Technical Information (OSTI)

    platforms for preclinical and field testing that utilize the assays developed in goal 1. We generated and characterized suitable primers more for West Nile Virus RNA detection. ...

  4. Tobacco mosaic virus: A biological building block for micro/nano...

    Office of Scientific and Technical Information (OSTI)

    Tobacco mosaic virus: A biological building block for micronanobio systems Citation Details In-Document Search Title: Tobacco mosaic virus: A biological building block for micro...

  5. Chimeric human parainfluenza virus bearing the Ebola virus glycoprotein as the sole surface protein is immunogenic and highly protective against Ebola virus challenge

    SciTech Connect (OSTI)

    Bukreyev, Alexander Marzi, Andrea; Feldmann, Friederike; Zhang Liqun; Dorward, David W.; Pickles, Raymond J.; Feldmann, Heinz; Collins, Peter L.

    2009-01-20

    We generated a new live-attenuated vaccine against Ebola virus (EBOV) based on a chimeric virus HPIV3/{delta}F-HN/EboGP that contains the EBOV glycoprotein (GP) as the sole transmembrane envelope protein combined with the internal proteins of human parainfluenza virus type 3 (HPIV3). Electron microscopy analysis of the virus particles showed that they have an envelope and surface spikes resembling those of EBOV and a particle size and shape resembling those of HPIV3. When HPIV3/{delta}F-HN/EboGP was inoculated via apical surface of an in vitro model of human ciliated airway epithelium, the virus was released from the apical surface; when applied to basolateral surface, the virus infected basolateral cells but did not spread through the tissue. Following intranasal (IN) inoculation of guinea pigs, scattered infected cells were detected in the lungs by immunohistochemistry, but infectious HPIV3/{delta}F-HN/EboGP could not be recovered from the lungs, blood, or other tissues. Despite the attenuation, the virus was highly immunogenic, and a single IN dose completely protected the animals against a highly lethal intraperitoneal challenge of guinea pig-adapted EBOV.

  6. A replication-deficient rabies virus vaccine expressing Ebola virus glycoprotein is highly attenuated for neurovirulence

    SciTech Connect (OSTI)

    Papaneri, Amy B.; Wirblich, Christoph; Cann, Jennifer A.; Cooper, Kurt; Jahrling, Peter B.; Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick MD, 21702 ; Schnell, Matthias J.; Blaney, Joseph E.

    2012-12-05

    We are developing inactivated and live-attenuated rabies virus (RABV) vaccines expressing Ebola virus (EBOV) glycoprotein for use in humans and endangered wildlife, respectively. Here, we further characterize the pathogenesis of the live-attenuated RABV/EBOV vaccine candidates in mice in an effort to define their growth properties and potential for safety. RABV vaccines expressing GP (RV-GP) or a replication-deficient derivative with a deletion of the RABV G gene (RV{Delta}G-GP) are both avirulent after intracerebral inoculation of adult mice. Furthermore, RV{Delta}G-GP is completely avirulent upon intracerebral inoculation of suckling mice unlike parental RABV vaccine or RV-GP. Analysis of RV{Delta}G-GP in the brain by quantitative PCR, determination of virus titer, and immunohistochemistry indicated greatly restricted virus replication. In summary, our findings indicate that RV-GP retains the attenuation phenotype of the live-attenuated RABV vaccine, and RV{Delta}G-GP would appear to be an even safer alternative for use in wildlife or consideration for human use.

  7. Structural basis for the antibody neutralization of Herpes simplex virus

    Office of Scientific and Technical Information (OSTI)

    (Journal Article) | SciTech Connect Structural basis for the antibody neutralization of Herpes simplex virus Citation Details In-Document Search Title: Structural basis for the antibody neutralization of Herpes simplex virus The gD-E317-Fab complex crystal revealed the conformational epitope of human mAb E317 on HSV gD, providing a molecular basis for understanding the viral neutralization mechanism. Glycoprotein D (gD) of Herpes simplex virus (HSV) binds to a host cell surface receptor,

  8. Virus Assemblies as Templates for Nanocircuits

    SciTech Connect (OSTI)

    James N Culver; Michael T Harris

    2011-08-31

    The goals of this project were directed at the identification and characterization of bio-mineralization processes and patterning methods for the development of nano scale materials and structures with novel energy and conductive traits. This project utilized a simple plant virus as a model template to investigate methods to attach and coat metals and other inorganic compounds onto biologically based nanotemplates. Accomplishments include: the development of robust biological nanotemplates with enhanced inorganic coating activities; novel coating strategies that allow for the deposition of a continuous inorganic layer onto a bio-nanotemplate even in the absence of a reducing agent; three-dimensional patterning methods for the assemble of nano-featured high aspect ratio surfaces and the demonstrated use of these surfaces in enhancing battery and energy storage applications. Combined results from this project have significantly advanced our understanding and ability to utilize the unique self-assembly properties of biologically based molecules to produce novel materials at the nanoscale level.

  9. Structure of the Ebola Virus Glycoprotein Bound to an Antibody...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Structure of the Ebola Virus Glycoprotein Bound to an Antibody from a Human Survivor Print Ebolavirus, one of two members of the family of filoviruses, causes a severe hemorrhagic...

  10. ALS Capabilities Reveal Multiple Functions of Ebola Virus

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Functions of Ebola Virus Print Friday, 13 June 2014 10:25 A central dogma of molecular biology is that a protein's sequence dictates its fold, and the fold dictates its function....

  11. Designer Proteins Target Epstein-Barr-Virus-Associated Cancer

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Designer Proteins Target Epstein-Barr-Virus-Associated Cancer Print Immortality is not a good thing for cells, and in fact, cells will destroy themselves in a process called...

  12. Nanomachines: How Viruses Work, and How We Can Stop Them

    ScienceCinema (OSTI)

    Carolyn Bertozzi

    2010-01-08

    Nature's Nasty Nanomachines: How Viruses Work, and How We Can Stop Them. Carolyn Bertozzi, director of Berkeley Lab's Molecular Foundry, discusses this topic at a Feb. 21, 2009 Nano*High talk.

  13. ALS Capabilities Reveal Multiple Functions of Ebola Virus

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    ALS Capabilities Reveal Multiple Functions of Ebola Virus ALS Capabilities Reveal Multiple Functions of Ebola Virus Print Friday, 13 June 2014 10:25 A central dogma of molecular biology is that a protein's sequence dictates its fold, and the fold dictates its function. Scientists typically expect that a protein has a singular structure (with some conformational variation), and that when an experimental structure is solved, it can used to understand the known biological function(s) of the

  14. Human immunodeficiency virus type 1 clade M mosaic gag polypeptides

    Office of Scientific and Technical Information (OSTI)

    (Patent) | SciTech Connect Patent: Human immunodeficiency virus type 1 clade M mosaic gag polypeptides Citation Details In-Document Search Title: Human immunodeficiency virus type 1 clade M mosaic gag polypeptides The present invention relates to mosaic HIV-1 group M Gag sequences and to a composition comprising same. Authors: Korber, Bette T ; Perkins, Simon ; Bhattacharya, Tanmoy ; Fischer, William M ; Theiler, James ; Letvin, Norman ; Haynes, Barton F ; Hahn, Beatrice H ; Yusim, Karina ;

  15. Multidisciplinary team aids understanding of Hepatitis C virus and possible

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    cure Multidisciplinary team aids understanding of Hepititus C virus Community Connections: Your link to news and opportunities from Los Alamos National Laboratory Latest Issue:Mar. 2016 all issues All Issues » submit Multidisciplinary team aids understanding of Hepatitis C virus and possible cure Computer simulations model cellular development. March 1, 2013 Centers for Disease Control World Map of Hepititus C Centers for Disease Control World Map of Hepatitis C. Contacts Editor Linda

  16. High molecular weight polysaccharide that binds and inhibits virus

    DOE Patents [OSTI]

    Konowalchuk, Thomas W

    2014-01-14

    This invention provides a high molecular weight polysaccharide capable of binding to and inhibiting virus and related pharmaceutical formulations and methods on inhibiting viral infectivity and/or pathogenicity, as well as immunogenic compositions. The invention further methods of inhibiting the growth of cancer cells and of ameliorating a symptom of aging. Additionally, the invention provides methods of detecting and/or quantifying and/or isolating viruses.

  17. Solid flexible electrochemical supercapacitor using Tobacco mosaic virus

    Office of Scientific and Technical Information (OSTI)

    nanostructures and ALD ruthenium oxide (Journal Article) | SciTech Connect Solid flexible electrochemical supercapacitor using Tobacco mosaic virus nanostructures and ALD ruthenium oxide Citation Details In-Document Search Title: Solid flexible electrochemical supercapacitor using Tobacco mosaic virus nanostructures and ALD ruthenium oxide Authors: Gnerlich, Markus ; Pomerantseva, Ekaterina ; Gregorczyk, Keith ; Ketchum, D ; Rubloff, Gary W ; Ghodssi, Reza Publication Date: 2013-10-24 OSTI

  18. Structure of the Newcastle disease virus hemagglutinin-neuraminidase (HN)

    Office of Scientific and Technical Information (OSTI)

    ectodomain reveals a four-helix bundle stalk (Journal Article) | SciTech Connect of the Newcastle disease virus hemagglutinin-neuraminidase (HN) ectodomain reveals a four-helix bundle stalk Citation Details In-Document Search Title: Structure of the Newcastle disease virus hemagglutinin-neuraminidase (HN) ectodomain reveals a four-helix bundle stalk The paramyxovirus hemagglutinin-neuraminidase (HN) protein plays multiple roles in viral entry and egress, including binding to sialic acid

  19. Dengue Virus Infection Perturbs Lipid Homeostasis in Infected Mosquito Cells

    SciTech Connect (OSTI)

    Perera, Rushika M.; Riley, Catherine; Isaac, Georgis; Hopf- Jannasch, Amber; Moore, Ronald J.; Weitz, Karl K.; Pasa-Tolic, Ljiljana; Metz, Thomas O.; Adamec, Jiri; Kuhn, Richard J.

    2012-03-22

    Dengue virus causes {approx}50-100 million infections per year and thus is considered one of the most aggressive arthropod-borne human pathogen worldwide. During its replication, dengue virus induces dramatic alterations in the intracellular membranes of infected cells. This phenomenon is observed both in human and vector-derived cells. Using high-resolution mass spectrometry of mosquito cells, we show that this membrane remodeling is directly linked to a unique lipid repertoire induced by dengue virus infection. Specifically, 15% of the metabolites detected were significantly different between DENV infected and uninfected cells while 85% of the metabolites detected were significantly different in isolated replication complex membranes. Furthermore, we demonstrate that intracellular lipid redistribution induced by the inhibition of fatty acid synthase, the rate-limiting enzyme in lipid biosynthesis, is sufficient for cell survival but is inhibitory to dengue virus replication. Lipids that have the capacity to destabilize and change the curvature of membranes as well as lipids that change the permeability of membranes are enriched in dengue virus infected cells. Several sphingolipids and other bioactive signaling molecules that are involved in controlling membrane fusion, fission, and trafficking as well as molecules that influence cytoskeletal reorganization are also up regulated during dengue infection. These observations shed light on the emerging role of lipids in shaping the membrane and protein environments during viral infections and suggest membrane-organizing principles that may influence virus-induced intracellular membrane architecture.

  20. Enteric viruses in a mangrove lagoon, survival and shellfish incidence

    SciTech Connect (OSTI)

    Lopez de Cardona, I.; Bermudez, M.; Billmire, E.; Hazen, T.C.

    1988-12-31

    Mangrove oysters (Crassostrea rhizophorae) were screened for enteric viruses. For 18 months oysters were collected from Cano Boqueron, a tropical mangrove lagoon on the southwest coast of Puerto Rico. This popular tourist resort has two primary sewage treatment plants which service 158 single family cabanas. In spite of the heavy seasonal input of sewage to Cano Boqueron and high densities of fecal coliform bacteria, enteric viruses were not detected in shellfish meat. Because no viruses were detected in the oysters, a virus survival study was performed. Poliovirus type 1 was placed in diffusion chambers in situ at two sites in Cano Boqueron. More than 95% of the poliovirus inactivation occurred within 24 h. Virus inactivation was significantly different by site, indicating different inactivation rates within the lagoon. Chamber studies done simultaneously with Escherichia coli did not reveal differences between sites. It is suggested that the sewage effluent had an antiviral effect in the absence of an antibacterial effect. This study demonstrates the importance for establishing microbial contamination standards for shellfish growing waters in the tropics based upon in situ studies with tropical species, e.g. mangrove oyster.

  1. Pandemic Flu Planning | Y-12 National Security Complex

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    on employee safety and communications. History of pandemics In 1918 and 1919, an Influenza Pandemic occurred in three waves in the United States. Learn more. Resources you can...

  2. FLU5A425 | netl.doe.gov

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    ... 2002; for five research teams) and Ocean Drilling Program Leg 204 (63 cores; ... in Leg 204 corehole. The current research is divided into four interrelated tasks. ...

  3. ORISE: Pandemic Flu Toolkits | How ORISE is Making a Difference

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    workshops that have been presented to the Asia-Pacific Economic Cooperation (APEC) and other nations around the world. By developing training toolkits and providing...

  4. Structure and Mutagenesis of the Parainfluenza Virus 5

    Office of Scientific and Technical Information (OSTI)

    Hemagglutinin-Neuraminidase Stalk Domain Reveals a Four-Helix Bundle and the Role of the Stalk in Fusion Promotion (Journal Article) | SciTech Connect and Mutagenesis of the Parainfluenza Virus 5 Hemagglutinin-Neuraminidase Stalk Domain Reveals a Four-Helix Bundle and the Role of the Stalk in Fusion Promotion Citation Details In-Document Search Title: Structure and Mutagenesis of the Parainfluenza Virus 5 Hemagglutinin-Neuraminidase Stalk Domain Reveals a Four-Helix Bundle and the Role of

  5. Development of simulation tools for virus shell assembly. Final report

    SciTech Connect (OSTI)

    Berger, Bonnie

    2001-01-05

    Prof. Berger's major areas of research have been in applying computational and mathematical techniques to problems in biology, and more specifically to problems in protein folding and genomics. Significant progress has been made in the following areas relating to virus shell assembly: development has been progressing on a second-generation self-assembly simulator which provides a more versatile and physically realistic model of assembly; simulations are being developed and applied to a variety of problems in virus assembly; and collaborative efforts have continued with experimental biologists to verify and inspire the local rules theory and the simulator. The group has also worked on applications of the techniques developed here to other self-assembling structures in the material and biological sciences. Some of this work has been conducted in conjunction with Dr. Sorin Istrail when he was at Sandia National Labs.

  6. Structural Rearrangement in Ebola Virus Protein VP40 Creates Multiple

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Functions | Stanford Synchrotron Radiation Lightsource Structural Rearrangement in Ebola Virus Protein VP40 Creates Multiple Functions Monday, March 31, 2014 Figure 1. Three structures of VP40. Top, a butterfly-shaped dimer structure critical for membrane trafficking. Middle, a rearranged hexameric structure essential for building and releasing nascent virions. Bottom, an RNA-binding octameric ring that controls transcription in infected cells. As x-ray crystallographers, we often assume

  7. ALS Capabilities Reveal Multiple Functions of Ebola Virus

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    ALS Capabilities Reveal Multiple Functions of Ebola Virus Print A central dogma of molecular biology is that a protein's sequence dictates its fold, and the fold dictates its function. Scientists typically expect that a protein has a singular structure (with some conformational variation), and that when an experimental structure is solved, it can used to understand the known biological function(s) of the protein. Recently, researchers used beamline capabilities at the ALS to demonstrate that a

  8. ALS Capabilities Reveal Multiple Functions of Ebola Virus

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    ALS Capabilities Reveal Multiple Functions of Ebola Virus Print A central dogma of molecular biology is that a protein's sequence dictates its fold, and the fold dictates its function. Scientists typically expect that a protein has a singular structure (with some conformational variation), and that when an experimental structure is solved, it can used to understand the known biological function(s) of the protein. Recently, researchers used beamline capabilities at the ALS to demonstrate that a

  9. ALS Capabilities Reveal Multiple Functions of Ebola Virus

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    ALS Capabilities Reveal Multiple Functions of Ebola Virus Print A central dogma of molecular biology is that a protein's sequence dictates its fold, and the fold dictates its function. Scientists typically expect that a protein has a singular structure (with some conformational variation), and that when an experimental structure is solved, it can used to understand the known biological function(s) of the protein. Recently, researchers used beamline capabilities at the ALS to demonstrate that a

  10. Virus-based Piezoelectric Energy Generation - Energy Innovation Portal

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Energy Storage Energy Storage Electricity Transmission Electricity Transmission Advanced Materials Advanced Materials Find More Like This Return to Search Virus-based Piezoelectric Energy Generation Lawrence Berkeley National Laboratory Contact LBL About This Technology Publications: PDF Document Publication Bacteriophage_Commercial Analysis_EERE_20130521 ps.pdf (1,100 KB) Technology Marketing Summary Researchers at Berkeley Lab have demonstrated that the piezoelectric and liquid-crystalline

  11. HIV virus spread and evolution studied through computer modeling

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    HIV and evolution studied through computer modeling HIV virus spread and evolution studied through computer modeling This approach distinguishes between susceptible and infected individuals to capture the full infection history, including contact tracing data for infected individuals. November 19, 2013 Scanning electron micrograph of HIV-1 budding (in green) from cultured lymphocytes. The image has been colored to highlight important features. Scanning electron micrograph of HIV-1 budding (in

  12. ALS Capabilities Reveal Multiple Functions of Ebola Virus

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    ALS Capabilities Reveal Multiple Functions of Ebola Virus Print A central dogma of molecular biology is that a protein's sequence dictates its fold, and the fold dictates its function. Scientists typically expect that a protein has a singular structure (with some conformational variation), and that when an experimental structure is solved, it can used to understand the known biological function(s) of the protein. Recently, researchers used beamline capabilities at the ALS to demonstrate that a

  13. Structure of the Ebola virus glycoprotein bound to an antibody from a human

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    survivor 8 Structure of the Ebola virus glycoprotein bound to an antibody from a human survivor Ebolavirus: The ebolavirus causes a severe hemorrhagic fever with 50-90% lethality for which no vaccines or treatments are yet available. The more frequent re-emergence of the virus, its high prevalence among wildlife, and ease of importation of the virus make it a significant public health concern. A team of researchers have recently determined the crystal structure of the oligomeric, viral

  14. West Nile virus isolated from Virginia opossum (Didelphis virginiana) in Northwest Missouri 2012

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Bosco-Lauth, Angela; Harmon, Jessica; Lash, R. Ryan; Weiss, Sonja; Langevin, Stanley; Savage, Harry; Marvin S. Godsey, Jr.; Burkhalter, Kristen; Root, J. Jeffrey; Gidlewski, Thomas; et al

    2014-12-01

    We describe the isolation of West Nile virus (WNV; Flaviviridae, flavivirus) from blood of a Virginia opossum (Didelphis virginiana) collected in northwestern Missouri, USA in August 2012. Furthermore, sequencing determined that the virus was related to lineage 1a WNV02 strains. We discuss the role of wildlife in WNV disease epidemiology.

  15. Venezuelan equine encephalitis virus entry mechanism requires late endosome formation and resists cell membrane cholesterol depletion

    SciTech Connect (OSTI)

    Kolokoltsov, Andrey A.; Fleming, Elisa H.; Davey, Robert A. . E-mail: radavey@utmb.edu

    2006-04-10

    Virus envelope proteins determine receptor utilization and host range. The choice of receptor not only permits specific targeting of cells that express it, but also directs the virus into specific endosomal trafficking pathways. Disrupting trafficking can result in loss of virus infectivity due to redirection of virions to non-productive pathways. Identification of the pathway or pathways used by a virus is, thus, important in understanding virus pathogenesis mechanisms and for developing new treatment strategies. Most of our understanding of alphavirus entry has focused on the Old World alphaviruses, such as Sindbis and Semliki Forest virus. In comparison, very little is known about the entry route taken by more pathogenic New World alphaviruses. Here, we use a novel contents mixing assay to identify the cellular requirements for entry of a New World alphavirus, Venezuelan equine encephalitis virus (VEEV). Expression of dominant negative forms of key endosomal trafficking genes shows that VEEV must access clathrin-dependent endocytic vesicles for membrane fusion to occur. Unexpectedly, the exit point is different from Old World alphaviruses that leave from early endosomes. Instead, VEEV also requires functional late endosomes. Furthermore, unlike the Old World viruses, VEEV entry is insensitive to cholesterol sequestration from cell membranes and may reflect a need to access an endocytic compartment that lacks cholesterol. This indicates fundamental differences in the entry route taken by VEEV compared to Old World alphaviruses.

  16. Inhibition of lytic infection of pseudorabies virus by arginine depletion

    SciTech Connect (OSTI)

    Wang, H.-C. [Department of Veterinary Medicine, College of Veterinary Medicine, National Chung-Hsing University, Taichung 402, Taiwan (China); Kao, Y.-C. [Department of Veterinary Medicine, College of Veterinary Medicine, National Chung-Hsing University, Taichung 402, Taiwan (China); Chang, T-J. [Department of Veterinary Medicine, College of Veterinary Medicine, National Chung-Hsing University, Taichung 402, Taiwan (China); Wong, M.-L. [Department of Veterinary Medicine, College of Veterinary Medicine, National Chung-Hsing University, Taichung 402, Taiwan (China)]. E-mail: mlwong@dragon.nchu.edu.tw

    2005-08-26

    Pseudorabies virus (PRV) is a member of Alphahepesviruses; it is an enveloped virus with a double-stranded DNA genome. Polyamines (such as spermine and spermidine) are ubiquitous in animal cells and participate in cellular proliferation and differentiation. Previous results of our laboratory showed that the PRV can accomplish lytic infection either in the presence of exogenous spermine (or spermidine) or depletion of cellular polyamines. The amino acid arginine is a precursor of polyamine biosynthesis. In this work, we investigated the role of arginine in PRV infection. It was found that the plaque formation of PRV was inhibited by arginase (enzyme catalyzing the conversion of arginine into ornithine and urea) treatment whereas this inhibition can be reversed by exogenous arginine, suggesting that arginine is essential for PRV proliferation. Western blotting was conducted to study the effect of arginine depletion on the levels of structural proteins of PRV in virus-infected cells. Four PRV structural proteins (gB, gE, UL47, and UL48) were chosen for examination, and results revealed that the levels of viral proteins were obviously reduced in long time arginase treatment. However, the overall protein synthesis machinery was apparently not influenced by arginase treatment either in mock or PRV-infected cells. Analyzing with native gel, we found that arginase treatment affected the mobility of PRV structural proteins, suggesting the conformational change of viral proteins by arginine depletion. Heat shock proteins, acting as molecular chaperons, participate in protein folding and translocation. Our results demonstrated that long time arginase treatment could reduce the expression of cellular heat shock proteins 70 (hsc70 and hsp70), and transcriptional suppression of heat shock protein 70 gene promoter was one of the mechanisms involved in this reduced expression.

  17. LINGUISTIC ANALYSIS OF THE NUCLEOPROTEIN GENE OF INFLUENZA A VIRUS

    SciTech Connect (OSTI)

    A. SKOURIKHINE; T. BURR

    2000-05-01

    We applied linguistic analysis approach, specifically N-grams, to classify nucleotide and amino acids sequences of nucleoprotein (NP) gene of the Influenza A virus isolated from a range of hosts and geographic regions. We considered letter frequency (1-grams), letter pairs frequency (2-grams) and triplets' frequency (3-grams). Classification trees based on 1,2,3-grams variables were constructed for the same NP nucleotide and amino acids strains and their classification efficiency were compared with the clustering obtained using phylogenetic analysis. The results have shown that disregarding positional information for a NP gene can provide the same level of recognition accuracy like alternative more complex classification techniques.

  18. Crystal structures of the reverse transcriptase-associated ribonuclease H domain of xenotropic murine leukemia-virus related virus

    SciTech Connect (OSTI)

    Zhou, Dongwen; Chung, Suhman; Miller, Maria; Le Grice, Stuart F.J.; Wlodawer, Alexander

    2012-06-19

    The ribonuclease H (RNase H) domain of retroviral reverse transcriptase (RT) plays a critical role in the life cycle by degrading the RNA strands of DNA/RNA hybrids. In addition, RNase H activity is required to precisely remove the RNA primers from nascent (-) and (+) strand DNA. We report here three crystal structures of the RNase H domain of xenotropic murine leukemia virus-related virus (XMRV) RT, namely (i) the previously identified construct from which helix C was deleted, (ii) the intact domain, and (iii) the intact domain complexed with an active site {alpha}-hydroxytropolone inhibitor. Enzymatic assays showed that the intact RNase H domain retained catalytic activity, whereas the variant lacking helix C was only marginally active, corroborating the importance of this helix for enzymatic activity. Modeling of the enzyme-substrate complex elucidated the essential role of helix C in binding a DNA/RNA hybrid and its likely mode of recognition. The crystal structure of the RNase H domain complexed with {beta}-thujaplicinol clearly showed that coordination by two divalent cations mediates recognition of the inhibitor.

  19. Non-coding RNAs and heme oxygenase-1 in vaccinia virus infection

    SciTech Connect (OSTI)

    Meseda, Clement A.; Srinivasan, Kumar; Wise, Jasen; Catalano, Jennifer; Yamada, Kenneth M.; Dhawan, Subhash

    2014-11-07

    Highlights: • Heme oxygenase-1 (HO-1) induction inhibited vaccinia virus infection of macrophages. • Reduced infectivity inversely correlated with increased expression of non-coding RNAs. • The regulation of HO-1 and ncRNAs suggests a novel host defense response against vaccinia virus infection. - Abstract: Small nuclear RNAs (snRNAs) are <200 nucleotide non-coding uridylate-rich RNAs. Although the functions of many snRNAs remain undetermined, a population of snRNAs is produced during the early phase of infection of cells by vaccinia virus. In the present study, we demonstrate a direct correlation between expression of the cytoprotective enzyme heme oxygenase-1 (HO-1), suppression of selective snRNA expression, and inhibition of vaccinia virus infection of macrophages. Hemin induced HO-1 expression, completely reversed virus-induced host snRNA expression, and suppressed vaccinia virus infection. This involvement of specific virus-induced snRNAs and associated gene clusters suggests a novel HO-1-dependent host-defense pathway in poxvirus infection.

  20. Structure of the Ebola Virus Glycoprotein Bound to an Antibody from a Human

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Survivor Structure of the Ebola Virus Glycoprotein Bound to an Antibody from a Human Survivor Print Ebolavirus, one of two members of the family of filoviruses, causes a severe hemorrhagic fever with 50-90% human mortality. That no vaccines or treatments are yet available combined with the frequent re-emergence of the virus, its high prevalence among wildlife, and ease of importation of the virus make it a significant public health concern. A team of researchers from the Scripps Research

  1. Structure of the Ebola Virus Glycoprotein Bound to an Antibody from a Human

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Survivor Structure of the Ebola Virus Glycoprotein Bound to an Antibody from a Human Survivor Print Ebolavirus, one of two members of the family of filoviruses, causes a severe hemorrhagic fever with 50-90% human mortality. That no vaccines or treatments are yet available combined with the frequent re-emergence of the virus, its high prevalence among wildlife, and ease of importation of the virus make it a significant public health concern. A team of researchers from the Scripps Research

  2. Structure of the Ebola Virus Glycoprotein Bound to an Antibody from a Human

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Survivor Structure of the Ebola Virus Glycoprotein Bound to an Antibody from a Human Survivor Print Ebolavirus, one of two members of the family of filoviruses, causes a severe hemorrhagic fever with 50-90% human mortality. That no vaccines or treatments are yet available combined with the frequent re-emergence of the virus, its high prevalence among wildlife, and ease of importation of the virus make it a significant public health concern. A team of researchers from the Scripps Research

  3. Structure of the Ebola Virus Glycoprotein Bound to an Antibody from a Human

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Survivor Structure of the Ebola Virus Glycoprotein Bound to an Antibody from a Human Survivor Structure of the Ebola Virus Glycoprotein Bound to an Antibody from a Human Survivor Print Wednesday, 26 November 2008 00:00 Ebolavirus, one of two members of the family of filoviruses, causes a severe hemorrhagic fever with 50-90% human mortality. That no vaccines or treatments are yet available combined with the frequent re-emergence of the virus, its high prevalence among wildlife, and ease of

  4. Structure of the Ebola Virus Glycoprotein Bound to an Antibody from a Human

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Survivor Structure of the Ebola Virus Glycoprotein Bound to an Antibody from a Human Survivor Print Ebolavirus, one of two members of the family of filoviruses, causes a severe hemorrhagic fever with 50-90% human mortality. That no vaccines or treatments are yet available combined with the frequent re-emergence of the virus, its high prevalence among wildlife, and ease of importation of the virus make it a significant public health concern. A team of researchers from the Scripps Research

  5. Genomics-enabled sensor platform for rapid detection of viruses related to

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    disease outbreak. (Technical Report) | SciTech Connect Genomics-enabled sensor platform for rapid detection of viruses related to disease outbreak. Citation Details In-Document Search Title: Genomics-enabled sensor platform for rapid detection of viruses related to disease outbreak. Bioweapons and emerging infectious diseases pose growing threats to our national security. Both natural disease outbreak and outbreaks due to a bioterrorist attack are a challenge to detect, taking days after the

  6. Genomics-enabled sensor platform for rapid detection of viruses related to

    Office of Scientific and Technical Information (OSTI)

    disease outbreak. (Technical Report) | SciTech Connect SciTech Connect Search Results Technical Report: Genomics-enabled sensor platform for rapid detection of viruses related to disease outbreak. Citation Details In-Document Search Title: Genomics-enabled sensor platform for rapid detection of viruses related to disease outbreak. Bioweapons and emerging infectious diseases pose growing threats to our national security. Both natural disease outbreak and outbreaks due to a bioterrorist attack

  7. Tobacco mosaic virus: A biological building block for micro/nano/bio

    Office of Scientific and Technical Information (OSTI)

    systems (Journal Article) | SciTech Connect Tobacco mosaic virus: A biological building block for micro/nano/bio systems Citation Details In-Document Search Title: Tobacco mosaic virus: A biological building block for micro/nano/bio systems Authors: Fan, Xiao Z ; Pomerantseva, Ekaterina ; Gnerlich, Markus ; Brown, Adam ; Gerasopoulos, K ; McCarthy, M ; Culver, James ; Ghodssi, Reza Publication Date: 2013-01-01 OSTI Identifier: 1160750 DOE Contract Number: SC0001160 Resource Type: Journal

  8. Chimeric SV40 virus-like particles induce specific cytotoxicity and protective immunity against influenza A virus without the need of adjuvants

    SciTech Connect (OSTI)

    Kawano, Masaaki; Morikawa, Katsuma; Suda, Tatsuya; Ohno, Naohito; Matsushita, Sho; Akatsuka, Toshitaka; Handa, Hiroshi; Matsui, Masanori

    2014-01-05

    Virus-like particles (VLPs) are a promising vaccine platform due to the safety and efficiency. However, it is still unclear whether polyomavirus-based VLPs are useful for this purpose. Here, we attempted to evaluate the potential of polyomavirus VLPs for the antiviral vaccine using simian virus 40 (SV40). We constructed chimeric SV40-VLPs carrying an HLA-A{sup ⁎}02:01-restricted, cytotoxic T lymphocyte (CTL) epitope derived from influenza A virus. HLA-A{sup ⁎}02:01-transgenic mice were then immunized with the chimeric SV40-VLPs. The chimeric SV40-VLPs effectively induced influenza-specific CTLs and heterosubtypic protection against influenza A viruses without the need of adjuvants. Because DNase I treatment of the chimeric SV40-VLPs did not disrupt CTL induction, the intrinsic adjuvant property may not result from DNA contaminants in the VLP preparation. In addition, immunization with the chimeric SV40-VLPs generated long-lasting memory CTLs. We here propose that the chimeric SV40-VLPs harboring an epitope may be a promising CTL-based vaccine platform with self-adjuvant properties. - Highlights: ‱ We constructed chimeric SV40-VLPs carrying an influenza virus-derived CTL epitope. ‱ Chimeric SV40-VLPs induce influenza-specific CTLs in mice without adjuvants. ‱ Chimeric SV40-VLPs induce heterosubtypic protection against influenza A viruses. ‱ Chimeric SV40-VLPs induce long-lasting memory CTLs. ‱ Chimeric SV40-VLPs is a promising vaccine platform with self-adjuvant properties.

  9. Human monoclonal antibodies derived from a patient infected with 2009 pandemic influenza A virus broadly cross-neutralize group 1 influenza viruses

    SciTech Connect (OSTI)

    Pan, Yang; Sasaki, Tadahiro; Du, Anariwa; and others

    2014-07-18

    Highlights: • Influenza infection can elicit heterosubtypic antibodies to group 1 influenza virus. • Three human monoclonal antibodies were generated from an H1N1-infected patient. • The antibodies predominantly recognized ?-helical stem of viral hemagglutinin (HA). • The antibodies inhibited HA structural activation during the fusion process. • The antibodies are potential candidates for future antibody therapy to influenza. - Abstract: Influenza viruses are a continuous threat to human public health because of their ability to evolve rapidly through genetic drift and reassortment. Three human monoclonal antibodies (HuMAbs) were generated in this study, 1H11, 2H5 and 5G2, and they cross-neutralize a diverse range of group 1 influenza A viruses, including seasonal H1N1, 2009 pandemic H1N1 (H1N1pdm) and avian H5N1 and H9N2. The three HuMAbs were prepared by fusing peripheral blood lymphocytes from an H1N1pdm-infected patient with a newly developed fusion partner cell line, SPYMEG. All the HuMAbs had little hemagglutination inhibition activity but had strong membrane-fusion inhibition activity against influenza viruses. A protease digestion assay showed the HuMAbs targeted commonly a short ?-helix region in the stalk of the hemagglutinin. Furthermore, Ile45Phe and Glu47Gly double substitutions in the ?-helix region made the HA unrecognizable by the HuMAbs. These two amino acid residues are highly conserved in the HAs of H1N1, H5N1 and H9N2 viruses. The HuMAbs reported here may be potential candidates for the development of therapeutic antibodies against group 1 influenza viruses.

  10. 2012 Feature Stories | NREL

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Cell Pushes Efficiency Higher Award-Winning PV Cell Pushes Efficiency Higher NREL and Solar Junction outsmart the solar spectrum and set a world record with a 44%-efficient solar...

  11. 2012 News | Awards and Honors | NREL

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    RSS. December 28, 2012 Award-Winning PV Cell Pushes Efficiency Higher NREL and Solar Junction outsmart the solar spectrum and set a world record with a 44%-efficient solar cell....

  12. Adaptive immunity and histopathology in frog virus 3-infected Xenopus

    SciTech Connect (OSTI)

    Robert, Jacques . E-mail: robert@mail.rochester.edu; Morales, Heidi; Buck, Wayne; Cohen, Nicholas; Marr, Shauna; Gantress, Jennifer

    2005-02-20

    Xenopus has been used as an experimental model to evaluate the contribution of adaptive cellular immunity in amphibian host susceptibility to the emerging ranavirus FV3. Conventional histology and immunohistochemistry reveal that FV3 has a strong tropism for the proximal tubular epithelium of the kidney and is rarely disseminated elsewhere in Xenopus hosts unless their immune defenses are impaired or developmentally immature as in larvae. In such cases, virus is found widespread in most tissues. Adults, immunocompromised by depletion of CD8{sup +} T cells or by sub-lethal {gamma}-irradiation, show increased susceptibility to FV3 infection. Larvae and irradiated (but not normal) adults can be cross-infected through water by infected adult conspecifics (irradiated or not). The natural MHC class I deficiency and the absence of effect of anti-CD8 treatment on both larval CD8{sup +} T cells and larval susceptibility to FV3 are consistent with an inefficient CD8{sup +} T cell effector function during this developmental period.

  13. Selective destruction of cells infected with human immunodeficiency virus

    DOE Patents [OSTI]

    Keener, William K.; Ward, Thomas E.

    2003-09-30

    Compositions and methods for selectively killing a cell containing a viral protease are disclosed. The composition is a variant of a protein synthesis inactivating toxin wherein a viral protease cleavage site is interposed between the A and B chains. The variant of the type II ribosome-inactivating protein is activated by digestion of the viral protease cleavage site by the specific viral protease. The activated ribosome-inactivating protein then kills the cell by inactivating cellular ribosomes. A preferred embodiment of the invention is specific for human immunodeficiency virus (HIV) and uses ricin as the ribosome-inactivating protein. In another preferred embodiment of the invention, the variant of the ribosome-inactivating protein is modified by attachment of one or more hydrophobic agents. The hydrophobic agent facilitates entry of the variant of the ribosome-inactivating protein into cells and can lead to incorporation of the ribosome-inactivating protein into viral particles. Still another preferred embodiment of the invention includes a targeting moiety attached to the variants of the ribosome-inactivating protein to target the agent to HIV infectable cells.

  14. Selective Destruction Of Cells Infected With The Human Immunodeficiency Virus

    DOE Patents [OSTI]

    Keener, William K.; Ward, Thomas E.

    2006-03-28

    Compositions and methods for selectively killing a cell containing a viral protease are disclosed. The composition is a varient of a protein synthesis inactivating toxin wherein a viral protease cleavage site is interposed between the A and B chains. The variant of the type II ribosome-inactivating protein is activated by digestion of the viral protease cleavage site by the specific viral protease. The activated ribosome-inactivating protein then kills the cell by inactivating cellular ribosomes. A preferred embodiment of the invention is specific for human immunodeficiency virus (HIV) and uses ricin as the ribosome-inactivating protein. In another preferred embodiment of the invention, the variant of the ribosome-inactivating protein is modified by attachment of one or more hydrophobic agents. The hydrophobic agent facilitates entry of the variant of the ribosome-inactivating protein into cells and can lead to incorporation of the ribosome-inactivating protein into viral particles. Still another preferred embodiment of the invention includes a targeting moiety attached to the variants of the ribosome-inactivating protein to target the agent to HIV infectable cells.

  15. Crystal Structure of a Virus-Encoded Putative Glycosyltransferase

    SciTech Connect (OSTI)

    Xiang, Ye; Baxa, Ulrich; Zhang, Ying; Steven, Alasdair C.; Lewis, Gentry L.; Van Etten, James L.; Rossmann, Michael G.

    2010-11-22

    The chloroviruses (family Phycodnaviridae), unlike most viruses, encode some, if not most, of the enzymes involved in the glycosylation of their structural proteins. Annotation of the gene product B736L from chlorovirus NY-2A suggests that it is a glycosyltransferase. The structure of the recombinantly expressed B736L protein was determined by X-ray crystallography to 2.3-{angstrom} resolution, and the protein was shown to have two nucleotide-binding folds like other glycosyltransferase type B enzymes. This is the second structure of a chlorovirus-encoded glycosyltransferase and the first structure of a chlorovirus type B enzyme to be determined. B736L is a retaining enzyme and belongs to glycosyltransferase family 4. The donor substrate was identified as GDP-mannose by isothermal titration calorimetry and was shown to bind into the cleft between the two domains in the protein. The active form of the enzyme is probably a dimer in which the active centers are separated by about 40 {angstrom}.

  16. P1-Substituted Symmetry-Based Human Immunodeficiency Virus Protease Inhibitors with Potent Antiviral Activity against Drug-Resistant Viruses

    SciTech Connect (OSTI)

    DeGoey, David A.; Grampovnik, David J.; Chen, Hui-Ju; Flosi, William J.; Klein, Larry L.; Dekhtyar, Tatyana; Stoll, Vincent; Mamo, Mulugeta; Molla, Akhteruzzaman; Kempf, Dale J.

    2013-03-07

    Because there is currently no cure for HIV infection, patients must remain on long-term drug therapy, leading to concerns over potential drug side effects and the emergence of drug resistance. For this reason, new and safe antiretroviral agents with improved potency against drug-resistant strains of HIV are needed. A series of HIV protease inhibitors (PIs) with potent activity against both wild-type (WT) virus and drug-resistant strains of HIV was designed and synthesized. The incorporation of substituents with hydrogen bond donor and acceptor groups at the P1 position of our symmetry-based inhibitor series resulted in significant potency improvements against the resistant mutants. By this approach, several compounds, such as 13, 24, and 29, were identified that demonstrated similar or improved potencies compared to 1 against highly mutated strains of HIV derived from patients who previously failed HIV PI therapy. Overall, compound 13 demonstrated the best balance of potency against drug resistant strains of HIV and oral bioavailability in pharmacokinetic studies. X-ray analysis of an HIV PI with an improved resistance profile bound to WT HIV protease is also reported.

  17. Rapid detection of Ebola virus with a reagent-free, point-of-care biosensor

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Baca, Justin T.; Severns, Virginia; Lovato, Debbie; Branch, Darren W.; Larson, Richard S.

    2015-04-14

    Surface acoustic wave (SAW) sensors can rapidly detect Ebola antigens at the point-of-care without the need for added reagents, sample processing, or specialized personnel. This preliminary study demonstrates SAW biosensor detection of the Ebola virus in a concentration-dependent manner. The detection limit with this methodology is below the average level of viremia detected on the first day of symptoms by PCR. We observe a log-linear sensor response for highly fragmented Ebola viral particles, with a detection limit corresponding to 1.9 × 10⁎ PFU/mL prior to virus inactivation. We predict greatly improved sensitivity for intact, infectious Ebola virus. This point-of-care methodologymore » has the potential to detect Ebola viremia prior to symptom onset, greatly enabling infection control and rapid treatment. This biosensor platform is powered by disposable AA batteries and can be rapidly adapted to detect other emerging diseases in austere conditions.« less

  18. Rapid detection of Ebola virus with a reagent-free, point-of-care biosensor

    SciTech Connect (OSTI)

    Baca, Justin T.; Severns, Virginia; Lovato, Debbie; Branch, Darren W.; Larson, Richard S.

    2015-04-14

    Surface acoustic wave (SAW) sensors can rapidly detect Ebola antigens at the point-of-care without the need for added reagents, sample processing, or specialized personnel. This preliminary study demonstrates SAW biosensor detection of the Ebola virus in a concentration-dependent manner. The detection limit with this methodology is below the average level of viremia detected on the first day of symptoms by PCR. We observe a log-linear sensor response for highly fragmented Ebola viral particles, with a detection limit corresponding to 1.9 Ś 10? PFU/mL prior to virus inactivation. We predict greatly improved sensitivity for intact, infectious Ebola virus. This point-of-care methodology has the potential to detect Ebola viremia prior to symptom onset, greatly enabling infection control and rapid treatment. This biosensor platform is powered by disposable AA batteries and can be rapidly adapted to detect other emerging diseases in austere conditions.

  19. Three dimensional colorimetric assay assemblies

    DOE Patents [OSTI]

    Charych, Deborah (Albany, CA); Reichart, Anke (Albany, CA)

    2000-01-01

    A direct assay is described using novel three-dimensional polymeric assemblies which change from a blue to red color when exposed to an analyte, in one case a flu virus. The assemblies are typically in the form of liposomes which can be maintained in a suspension, and show great intensity in their color changes. Their method of production is also described.

  20. Apple latent spherical virus vectors for reliable and effective virus-induced gene silencing among a broad range of plants including tobacco, tomato, Arabidopsis thaliana, cucurbits, and legumes

    SciTech Connect (OSTI)

    Igarashi, Aki; Yamagata, Kousuke; Sugai, Tomokazu; Takahashi, Yukari; Sugawara, Emiko; Tamura, Akihiro; Yaegashi, Hajime; Yamagishi, Noriko; Takahashi, Tsubasa; Isogai, Masamichi; Takahashi, Hideki; Yoshikawa, Nobuyuki

    2009-04-10

    Apple latent spherical virus (ALSV) vectors were evaluated for virus-induced gene silencing (VIGS) of endogenous genes among a broad range of plant species. ALSV vectors carrying partial sequences of a subunit of magnesium chelatase (SU) and phytoene desaturase (PDS) genes induced highly uniform knockout phenotypes typical of SU and PDS inhibition on model plants such as tobacco and Arabidopsis thaliana, and economically important crops such as tomato, legume, and cucurbit species. The silencing phenotypes persisted throughout plant growth in these plants. In addition, ALSV vectors could be successfully used to silence a meristem gene, proliferating cell nuclear antigen and disease resistant N gene in tobacco and RCY1 gene in A. thaliana. As ALSV infects most host plants symptomlessly and effectively induces stable VIGS for long periods, the ALSV vector is a valuable tool to determine the functions of interested genes among a broad range of plant species.

  1. Structure of the Newcastle disease virus F protein in the post-fusion conformation

    SciTech Connect (OSTI)

    Swanson, Kurt; Wen, Xiaolin; Leser, George P.; Paterson, Reay G.; Lamb, Robert A.; Jardetzky, Theodore S. (Stanford-MED); (NWU); (HHMI)

    2010-11-17

    The paramyxovirus F protein is a class I viral membrane fusion protein which undergoes a significant refolding transition during virus entry. Previous studies of the Newcastle disease virus, human parainfluenza virus 3 and parainfluenza virus 5 F proteins revealed differences in the pre- and post-fusion structures. The NDV Queensland (Q) F structure lacked structural elements observed in the other two structures, which are key to the refolding and fusogenic activity of F. Here we present the NDV Australia-Victoria (AV) F protein post-fusion structure and provide EM evidence for its folding to a pre-fusion form. The NDV AV F structure contains heptad repeat elements missing in the previous NDV Q F structure, forming a post-fusion six-helix bundle (6HB) similar to the post-fusion hPIV3 F structure. Electrostatic and temperature factor analysis of the F structures points to regions of these proteins that may be functionally important in their membrane fusion activity.

  2. A C. elegans-based foam for rapid on-site detection of residual live virus.

    SciTech Connect (OSTI)

    Negrete, Oscar A.; Branda, Catherine; Hardesty, Jasper O. E.; Tucker, Mark David; Kaiser, Julia N.; Kozina, Carol L.; Chirica, Gabriela S.

    2012-02-01

    In the response to and recovery from a critical homeland security event involving deliberate or accidental release of biological agents, initial decontamination efforts are necessarily followed by tests for the presence of residual live virus or bacteria. Such 'clearance sampling' should be rapid and accurate, to inform decision makers as they take appropriate action to ensure the safety of the public and of operational personnel. However, the current protocol for clearance sampling is extremely time-intensive and costly, and requires significant amounts of laboratory space and capacity. Detection of residual live virus is particularly problematic and time-consuming, as it requires evaluation of replication potential within a eukaryotic host such as chicken embryos. The intention of this project was to develop a new method for clearance sampling, by leveraging Sandia's expertise in the biological and material sciences in order to create a C. elegans-based foam that could be applied directly to the entire contaminated area for quick and accurate detection of any and all residual live virus by means of a fluorescent signal. Such a novel technology for rapid, on-site detection of live virus would greatly interest the DHS, DoD, and EPA, and hold broad commercial potential, especially with regard to the transportation industry.

  3. Lung Irradiation Increases Mortality After Influenza A Virus Challenge Occurring Late After Exposure

    SciTech Connect (OSTI)

    Manning, Casey M.; Johnston, Carl J.; Department of Pediatrics, University of Rochester Medical Center, Rochester, New York ; Reed, Christina K.; Lawrence, B. Paige; Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York ; Williams, Jacqueline P.; Finkelstein, Jacob N.

    2013-05-01

    Purpose: To address whether irradiation-induced changes in the lung environment alter responses to a viral challenge delivered late after exposure but before the appearance of late lung radiation injury. Methods and Materials: C57BL/6J mice received either lung alone or combined lung and whole-body irradiation (0-15 Gy). At 10 weeks after irradiation, animals were infected with 120 HAU influenza virus strain A/HKx31. Innate and adaptive immune cell recruitment was determined using flow cytometry. Cytokine and chemokine production and protein leakage into the lung after infection were assessed. Results: Prior irradiation led to a dose-dependent failure to regain body weight after infection and exacerbated mortality, but it did not affect virus-specific immune responses or virus clearance. Surviving irradiated animals displayed a persistent increase in total protein in bronchoalveolar lavage fluid and edema. Conclusions: Lung irradiation increased susceptibility to death after infection with influenza virus and impaired the ability to complete recovery. This altered response does not seem to be due to a radiation effect on the immune response, but it may possibly be an effect on epithelial repair.

  4. Identification of full-length transmitted/founder viruses and their progeny in primary HIV-1 infection

    SciTech Connect (OSTI)

    Korber, Bette; Hraber, Peter; Giorgi, Elena; Bhattacharya, T

    2009-01-01

    Identification of transmitted/founder virus genomes and their progeny by is a novel strategy for probing the molecular basis of HIV-1 transmission and for evaluating the genetic imprint of viral and host factors that act to constrain or facilitate virus replication. Here, we show in a cohort of twelve acutely infected subjects (9 clade B; 3 clade C), that complete genomic sequences of transmitted/founder viruses could be inferred using single genome amplification of plasma viral RNA, direct amplicon sequencing, and a model of random virus evolution. This allowed for the precise identification, chemical synthesis, molecular cloning, and biological analysis of those viruses actually responsible for productive clinical infection and for a comprehensive mapping of sequential viral genomes and proteomes for mutations that are necessary or incidental to the establishment of HIV-1 persistence. Transmitted/founder viruses were CD4 and CCR5 tropic, replicated preferentially in activated primary T-Iymphocytes but not monocyte-derived macrophages, and were effectively shielded from most heterologous or broadly neutralizing antibodies. By 3 months of infection, the evolving viral quasispecies in three subjects showed mutational fixation at only 2-5 discreet genomic loci. By 6-12 months, mutational fixation was evident at 18-27 genomic loci. Some, but not all, of these mutations were attributable to virus escape from cytotoxic Tlymphocytes or neutralizing antibodies, suggesting that other viral or host factors may influence early HIV -1 fitness.

  5. Surveillance for Western equine encephalitis St. Louis encephalitis and West Nile viruses using reverse transcription loop-mediated isothermal amplification

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Meagher, Robert J.; Ball, Cameron Scott; Langevin, Stanley A.; Fang, Ying; Wheeler, Sarah S.; Coffey, Lark L.

    2016-01-25

    In this study, collection of mosquitoes and testing for vector-borne viruses is a key surveillance activity that directly influences the vector control efforts of public health agencies, including determining when and where to apply insecticides. Vector control districts in California routinely monitor for three human pathogenic viruses including West Nile virus (WNV), Western equine encephalitis virus (WEEV), and St. Louis encephalitis virus (SLEV). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) offers highly sensitive and specific detection of these three viruses in a single multiplex reaction, but this technique requires costly, specialized equipment that is generally only available in centralized publicmore » health laboratories. We report the use of reverse transcription loop-mediated isothermal amplification (RT-LAMP) to detect WNV, WEEV, and SLEV RNA extracted from pooled mosquito samples collected in California, including novel primer sets for specific detection of WEEV and SLEV, targeting the nonstructural protein 4 (nsP4) gene of WEEV and the 3’ untranslated region (3’-UTR) of SLEV. Our WEEV and SLEV RT-LAMP primers allowed detection of <0.1 PFU/reaction of their respective targets in <30 minutes, and exhibited high specificity without cross reactivity when tested against a panel of alphaviruses and flaviviruses. Furthermore, the SLEV primers do not cross-react with WNV, despite both viruses being closely related members of the Japanese encephalitis virus complex. The SLEV and WEEV primers can also be combined in a single RT-LAMP reaction, with discrimination between amplicons by melt curve analysis. Although RT-qPCR is approximately one order of magnitude more sensitive than RT-LAMP for all three targets, the RT-LAMP technique is less instrumentally intensive than RT-qPCR and provides a more cost-effective method of vector-borne virus surveillance.« less

  6. Ocean Viruses: Tiny entities with Global Impacts ( JGI Seventh Annual User Meeting 2012: Genomics of Energy and Environment)

    ScienceCinema (OSTI)

    Sullivan, Matthew B [University of Arizona

    2013-01-15

    Matt Sullivan from the University of Arizona on "Ocean Viruses: Tiny Entities with Global Impacts" at the 7th Annual Genomics of Energy & Environment Meeting on March 22, 2012 in Walnut Creek, Calif.

  7. Ocean Viruses: Tiny entities with Global Impacts ( JGI Seventh Annual User Meeting 2012: Genomics of Energy and Environment)

    SciTech Connect (OSTI)

    Sullivan, Matthew B [University of Arizona] [University of Arizona

    2012-03-22

    Matt Sullivan from the University of Arizona on "Ocean Viruses: Tiny Entities with Global Impacts" at the 7th Annual Genomics of Energy & Environment Meeting on March 22, 2012 in Walnut Creek, Calif.

  8. Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses

    SciTech Connect (OSTI)

    Moody, M.  Anthony; Gao, Feng; Gurley, Thaddeus  C.; Amos, Joshua  D.; Kumar, Amit; Hora, Bhavna; Marshall, Dawn  J.; Whitesides, John  F.; Xia, Shi-Mao; Parks, Robert; Lloyd, Krissey  E.; Hwang, Kwan-Ki; Lu, Xiaozhi; Bonsignori, Mattia; Finzi, Andrés; Vandergrift, Nathan  A.; Alam, S.  Munir; Ferrari, Guido; Shen, Xiaoying; Tomaras, Georgia  D.; Kamanga, Gift; Cohen, Myron  S.; Sam, Noel  E.; Kapiga, Saidi; Gray, Elin S.; Tumba, Nancy  L.; Morris, Lynn; Zolla-Pazner, Susan; Gorny, Miroslaw  K.; Mascola, John  R.; Hahn, Beatrice H.; Shaw, George  M.; Sodroski, Joseph  G.; Liao, Hua-Xin; Montefiori, David C.; Hraber, Peter T.; Korber, Bette T.; Haynes, Barton F.

    2015-09-09

    The third variable (V3) loop and the CD4 binding site (CD4bs) of the viral envelope are frequently targeted by neutralizing antibodies (nAbs) in HIV-1-infected individuals. In chronic infection, virus escape mutants repopulate the plasma and V3 and CD4bs nAbs emerge that can neutralize heterologous tier 1 easy-to-neutralize, but not tier 2 difficult-to-neutralize HIV-1 isolates. However, neutralization sensitivity of autologous plasma viruses to this type of nAb response has not been studied. We describe the development and evolution in vivo of antibodies distinguished by their target specificity for V3and CD4bs epitopes on autologous tier 2 viruses but not on heterologous tier 2 viruses. A surprisingly high fraction of autologous circulating viruses was sensitive to these antibodies. These findings demonstrate a role for V3 and CD4bs antibodies in constraining the native envelope trimer in vivo to a neutralization-resistant phenotype, explaining why HIV-1 transmission generally occurs by tier 2 neutralization-resistant viruses.

  9. Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Moody, M.  Anthony; Gao, Feng; Gurley, Thaddeus  C.; Amos, Joshua  D.; Kumar, Amit; Hora, Bhavna; Marshall, Dawn  J.; Whitesides, John  F.; Xia, Shi-Mao; Parks, Robert; et al

    2015-09-09

    The third variable (V3) loop and the CD4 binding site (CD4bs) of the viral envelope are frequently targeted by neutralizing antibodies (nAbs) in HIV-1-infected individuals. In chronic infection, virus escape mutants repopulate the plasma and V3 and CD4bs nAbs emerge that can neutralize heterologous tier 1 easy-to-neutralize, but not tier 2 difficult-to-neutralize HIV-1 isolates. However, neutralization sensitivity of autologous plasma viruses to this type of nAb response has not been studied. We describe the development and evolution in vivo of antibodies distinguished by their target specificity for V3and CD4bs epitopes on autologous tier 2 viruses but not on heterologous tiermore » 2 viruses. A surprisingly high fraction of autologous circulating viruses was sensitive to these antibodies. These findings demonstrate a role for V3 and CD4bs antibodies in constraining the native envelope trimer in vivo to a neutralization-resistant phenotype, explaining why HIV-1 transmission generally occurs by tier 2 neutralization-resistant viruses.« less

  10. Transmitted virus fitness and host T cell responses collectively define divergent infection outcomes in two HIV-1 recipients

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Yue, Ling; Pfafferott, Katja J.; Baalwa, Joshua; Conrod, Karen; Dong, Catherine C.; Chui, Cecilia; Rong, Rong; Claiborne, Daniel T.; Prince, Jessica L.; Tang, Jianming; et al

    2015-01-08

    Control of virus replication in HIV-1 infection is critical to delaying disease progression. While cellular immune responses are a key determinant of control, relatively little is known about the contribution of the infecting virus to this process. To gain insight into this interplay between virus and host in viral control, we conducted a detailed analysis of two heterosexual HIV-1 subtype A transmission pairs in which female recipients sharing three HLA class I alleles exhibited contrasting clinical outcomes: R880F controlled virus replication while R463F experienced high viral loads and rapid disease progression. Near full-length single genome amplification defined the infecting transmitted/foundermore » (T/F) virus proteome and subsequent sequence evolution over the first year of infection for both acutely infected recipients. T/F virus replicative capacities were compared in vitro, while the development of the earliest cellular immune response was defined using autologous virus sequence-based peptides. The R880F T/F virus replicated significantly slower in vitro than that transmitted to R463F. While neutralizing antibody responses were similar in both subjects, during acute infection R880F mounted a broad T cell response, the most dominant components of which targeted epitopes from which escape was limited. In contrast, the primary HIV-specific T cell response in R463F was focused on just two epitopes, one of which rapidly escaped. This comprehensive study highlights both the importance of the contribution of the lower replication capacity of the transmitted/founder virus and an associated induction of a broad primary HIV-specific T cell response, which was not undermined by rapid epitope escape, to long-term viral control in HIV-1 infection. It underscores the importance of the earliest CD8 T cell response targeting regions of the virus proteome that cannot mutate without a high fitness cost, further emphasizing the need for vaccines that elicit a breadth of T cell responses to conserved viral epitopes.« less

  11. Recombination enhances HIV-1 envelope diversity by facilitating the survival of latent genomic fragments in the plasma virus population

    SciTech Connect (OSTI)

    Immonen, Taina T.; Conway, Jessica M.; Romero-Severson, Ethan O.; Perelson, Alan S.; Leitner, Thomas; Kouyos, Roger Dimitri

    2015-12-22

    HIV-1 is subject to immune pressure exerted by the host, giving variants that escape the immune response an advantage. Virus released from activated latent cells competes against variants that have continually evolved and adapted to host immune pressure. Nevertheless, there is increasing evidence that virus displaying a signal of latency survives in patient plasma despite having reduced fitness due to long-term immune memory. We investigated the survival of virus with latent envelope genomic fragments by simulating within-host HIV-1 sequence evolution and the cycling of viral lineages in and out of the latent reservoir. Our model incorporates a detailed mutation process including nucleotide substitution, recombination, latent reservoir dynamics, diversifying selection pressure driven by the immune response, and purifying selection pressure asserted by deleterious mutations. We evaluated the ability of our model to capture sequence evolution in vivo by comparing our simulated sequences to HIV-1 envelope sequence data from 16 HIV-infected untreated patients. Empirical sequence divergence and diversity measures were qualitatively and quantitatively similar to those of our simulated HIV-1 populations, suggesting that our model invokes realistic trends of HIV-1 genetic evolution. Moreover, reconstructed phylogenies of simulated and patient HIV-1 populations showed similar topological structures. Our simulation results suggest that recombination is a key mechanism facilitating the persistence of virus with latent envelope genomic fragments in the productively infected cell population. Recombination increased the survival probability of latent virus forms approximately 13-fold. Prevalence of virus with latent fragments in productively infected cells was observed in only 2% of simulations when we ignored recombination, while the proportion increased to 27% of simulations when we allowed recombination. We also found that the selection pressures exerted by different fitness landscapes influenced the shape of phylogenies, diversity trends, and survival of virus with latent genomic fragments. Furthermore, our model predicts that the persistence of latent genomic fragments from multiple different ancestral origins increases sequence diversity in plasma for reasonable fitness landscapes.

  12. Structure of the paramyxovirus parainfluenza virus 5 nucleoprotein-?RNA complex

    SciTech Connect (OSTI)

    Alayyoubi, Maher; Leser, George P.; Kors, Christopher A.; Lamb, Robert A.

    2015-04-07

    Parainfluenza virus 5 (PIV5) is a member of the Paramyxoviridae family of membrane-enveloped viruses with a negative-sense RNA genome that is packaged and protected by long filamentous nucleocapsid-helix structures (RNPs). These RNPs, consisting of ~2,600 protomers of nucleocapsid (N) protein, form the template for viral transcription and replication. We have determined the 3D X-ray crystal structure of the nucleoprotein (N)-RNA complex from PIV5 to 3.11-Ć resolution. The structure reveals a 13-mer nucleocapsid ring whose diameter, cavity, and pitch/height dimensions agree with EM data from early studies on the Paramyxovirinae subfamily of native RNPs, indicating that it closely represents one-turn in the building block of the RNP helices. The PIV5-N nucleocapsid ring encapsidates a nuclease resistant 78-nt RNA strand in its positively charged groove formed between the N-terminal (NTD) and C-terminal (CTD) domains of its successive N protomers. Six nucleotides precisely are associated with each N protomer, with alternating three-base-in three-base-out conformation. The binding of six nucleotides per protomer is consistent with the "rule of six" that governs the genome packaging of the Paramyxovirinae subfamily of viruses. PIV5-N protomer subdomains are very similar in structure to the previously solved Nipah-N structure, but with a difference in the angle between NTD/CTD at the RNA hinge region. Based on the Nipah-N structure we modeled a PIV5-N open conformation in which the CTD rotates away from the RNA strand into the inner spacious nucleocapsid-ring cavity. This rotation would expose the RNA for the viral polymerase activity without major disruption of the nucleocapsid structure.

  13. Dynamics of lipid droplets induced by the hepatitis C virus core protein

    SciTech Connect (OSTI)

    Lyn, Rodney K.; Department of Chemistry, University of Ottawa, Ottawa ; Kennedy, David C.; Stolow, Albert; Ridsdale, Andrew; Pezacki, John Paul

    2010-09-03

    Research highlights: {yields} Hepatitis C virus uses lipid droplets (LD) onto which HCV core proteins bind. {yields} HCV core proteins on LDs facilitate viral particle assembly. {yields} We used a novel combination of CARS, two-photon fluorescence, and DIC microscopies. {yields} Particle tracking experiments show that core slowly affects LD localization. {yields} Particle tracking measured the change in speed and directionality of LD movement. -- Abstract: The hepatitis C virus (HCV) is a global health problem, with limited treatment options and no vaccine available. HCV uses components of the host cell to proliferate, including lipid droplets (LD) onto which HCV core proteins bind and facilitate viral particle assembly. We have measured the dynamics of HCV core protein-mediated changes in LDs and rates of LD movement on microtubules using a combination of coherent anti-Stokes Raman scattering (CARS), two-photon fluorescence (TPF), and differential interference contrast (DIC) microscopies. Results show that the HCV core protein induces rapid increases in LD size. Particle tracking experiments show that HCV core protein slowly affects LD localization by controlling the directionality of LD movement on microtubules. These dynamic processes ultimately aid HCV in propagating and the molecules and interactions involved represent novel targets for potential therapeutic intervention.

  14. Synergized resmethrin and corticosterone alter the chicken's response to west nile virus

    SciTech Connect (OSTI)

    Jankowski, Mark David; Franson, J Christian; Mostl, Erich; Porter, Warren P; Hofmeister, Erik K

    2009-01-01

    Debate concerning arbovirus control strategies remains contentious because concern regarding the relative risk of viral infection and environmental toxicant exposure is high but inadequately characterized. Taking this into account, mosquito control agencies employ aerial insecticides only after arbovirus surveillance data indicate high local mosquito-infection-rates. Successfully mitigating the risk of adult-mosquito-control insecticides ('adulticides') to non-target species such as humans, domestic animals, fish, beneficial insects and wildlife, while increasing their efficacy to reduce arbovirus outbreak intensity requires targeted scientific data from animal toxicity studies and environmental monitoring activities. Wild birds are an important reservoir host for WNv and are potentially exposed to insecticides used for mosquito control. However, no risk assessments have evaluated whether insecticides augment or extend the potential transmissibility of West Nile virus (WNv) in birds. In order to augment existing resmethrin risk assessments, we aimed to determine whether synergized resmethrin (SR) may cause chickens to develop an elevated or extended WN viremia and if subacute stress may affect its immunotoxicity. We distributed 40 chickens into four groups then exposed them prior to and during WNv infection with SR (50 {mu}g/l resmethrin + 150 {mu}g/l piperonyl butoxide) and/or 20 mg/I corticosterone (CORT) in their drinking-water. Corticosterone was given for 10 continuous days and SR was given for 3 alternate days starting the 3rd day of CORT exposure, then chickens were subcutaneously inoculated with WNv on the 5th day of CORT treatment. Compared to controls, CORT treatment extended and elevated viremia, enhanced WNv-specific antibody and increased the percentage of birds that shed oral virus, whereas SR treatment extended viremia, depressed WNv-specific IgG, and increased the percentage of CORT-treated birds that shed oral virus. Corticosterone and SR independently and interactively altered immunity to WNv in chickens. Further characterization of how variations in SR-exposure to and CORT levels in chickens and wild birds relate to laboratory WNv-infection trials is warranted in order to place these findings into an epidemiological context.

  15. Improving the Capacity of Sodium Ion Battery Using a Virus-Templated Nanostructured Composite Cathode

    SciTech Connect (OSTI)

    Moradi, M; Li, Z; Qi, JF; Xing, WT; Xiang, K; Chiang, YM; Belcher, AM

    2015-05-01

    In this work we investigated an energy-efficient biotemplated route to synthesize nanostructured FePO4 for sodium-based batteries. Self-assembled M13 viruses and single wall carbon nanotubes (SWCNTs) have been used as a template to grow amorphous FePO4 nanoparticles at room temperature (the active composite is denoted as Bio-FePO4-CNT) to enhance the electronic conductivity of the active material. Preliminary tests demonstrate a discharge capacity as high as 166 mAh/g at C/10 rate, corresponding to composition Na0.9FePO4, which along with higher C-rate tests show this material to have the highest capacity and power performance reported for amorphous FePO4 electrodes to date.

  16. Relative concordance of human immunodeficiency virus oligomeric and monomeric envelope in CCR5 coreceptor usage

    SciTech Connect (OSTI)

    Teeravechyan, Samaporn; Suphaphiphat, Pirada; Essex, Max; Lee, Tun-Hou

    2008-01-20

    A major difference between binding and fusion assays commonly used to study the human immunodeficiency virus (HIV) envelope is the use of monomeric envelope for the former assay and oligomeric envelope for the latter. Due to discrepancies in their readouts for some mutants, envelope regions involved in CCR5 coreceptor usage were systematically studied to determine whether the discordance is due to inherent differences between the two assays or whether it genuinely reflects functional differences at each entry step. By adding the binding inhibitor TAK-779 to delay coreceptor binding kinetics in the fusion assay, the readouts were found comparable between the assays for the mutants analysed in this study. Our finding indicates that monomeric binding reflects oligomeric envelope-CCR5 interaction, thus discordant results between binding and fusion assays do not necessarily indicate differences in coreceptor usage by oligomeric envelope and monomeric gp120.

  17. Cell cycle regulation of human immunodeficiency virus type 1 integration in T cells: antagonistic effects of nuclear envelope breakdown and chromatin condensation

    SciTech Connect (OSTI)

    Mannioui, Abdelkrim . E-mail: karim.mannioui@chu-stlouis.fr; Schiffer, Cecile . E-mail: cecile.schiffer@voila.fr; Felix, Nathalie . E-mail: nathalie.felix@chu-stlouis.fr

    2004-11-10

    We examined the influence of mitosis on the kinetics of human immunodeficiency virus type 1 integration in T cells. Single-round infection of cells arrested in G1b or allowed to synchronously proceed through division showed that mitosis delays virus integration until 18-24 h postinfection, whereas integration reaches maximum levels by 15 h in G1b-arrested cells. Subcellular fractionation of metaphase-arrested cells indicated that, while nuclear envelope disassembly facilitates docking of viral DNA to chromatin, chromosome condensation directly antagonizes and therefore delays integration. As a result of the balance between the two effects, virus integration efficiency is eventually up to threefold greater in dividing cells. At the single-cell level, using a green fluorescent protein-expressing reporter virus, we found that passage through mitosis leads to prominent asymmetric segregation of the viral genome in daughter cells without interfering with provirus expression.

  18. Iowa State University | OSTI, US Dept of Energy, Office of Scientific and

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Technical Information Iowa State University Spotlights Home DOE Applauds ISU Science and Technical Programs Ames Laboratory is a DOE National Laboratory operated under contract by Iowa State University Physicist developing, improving designer optical materials Chemists discover proton mechanism used by flu virus to infect cells ISU, Ames Lab's Bryden & McCorkle win 2010 R&D 100 Award New tool for cell research may help unravel secrets of disease Beardshear Hall ISU's vision is to

  19. Identification of the heparin binding site on adeno-associated virus serotype 3B (AAV-3B)

    SciTech Connect (OSTI)

    Lerch, Thomas F.; Chapman, Michael S.

    2012-02-05

    Adeno-associated virus is a promising vector for gene therapy. In the current study, the binding site on AAV serotype 3B for the heparan sulfate proteoglycan (HSPG) receptor has been characterized. X-ray diffraction identified a disaccharide binding site at the most positively charged region on the virus surface. The contributions of basic amino acids at this and other sites were characterized using site-directed mutagenesis. Both heparin and cell binding are correlated to positive charge at the disaccharide binding site, and transduction is significantly decreased in AAV-3B vectors mutated at this site to reduce heparin binding. While the receptor attachment sites of AAV-3B and AAV-2 are both in the general vicinity of the viral spikes, the exact amino acids that participate in electrostatic interactions are distinct. Diversity in the mechanisms of cell attachment by AAV serotypes will be an important consideration for the rational design of improved gene therapy vectors.

  20. Identification of the heparin binding site on adeno-associated virus serotype 3B (AAV-3B)

    SciTech Connect (OSTI)

    Lerch, Thomas F.; Chapman, Michael S.

    2012-05-24

    Adeno-associated virus is a promising vector for gene therapy. In the current study, the binding site on AAV serotype 3B for the heparan sulfate proteoglycan (HSPG) receptor has been characterized. X-ray diffraction identified a disaccharide binding site at the most positively charged region on the virus surface. The contributions of basic amino acids at this and other sites were characterized using site-directed mutagenesis. Both heparin and cell binding are correlated to positive charge at the disaccharide binding site, and transduction is significantly decreased in AAV-3B vectors mutated at this site to reduce heparin binding. While the receptor attachment sites of AAV-3B and AAV-2 are both in the general vicinity of the viral spikes, the exact amino acids that participate in electrostatic interactions are distinct. Diversity in the mechanisms of cell attachment by AAV serotypes will be an important consideration for the rational design of improved gene therapy vectors.

  1. Towards understanding of Nipah virus attachment protein assembly and the role of protein affinity and crowding for membrane curvature events.

    SciTech Connect (OSTI)

    Stachowiak, Jeanne C.; Hayden, Carl C.; Negrete, Oscar A.; Davis, Ryan Wesley; Sasaki, Darryl Yoshio

    2013-10-01

    Pathogenic viruses are a primary threat to our national security and to the health and economy of our world. Effective defense strategies to combat viral infection and spread require the development of understanding of the mechanisms that these pathogens use to invade the host cell. We present in this report results of our research into viral particle recognition and fusion to cell membranes and the role that protein affinity and confinement in lipid domains plays in membrane curvature in cellular fusion and fission events. Herein, we describe 1) the assembly of the G attachment protein of Nipah virus using point mutation studies to define its role in viral particle fusion to the cell membrane, 2) how lateral pressure of membrane bound proteins induce curvature in model membrane systems, and 3) the role of membrane curvature in the selective partitioning of molecular receptors and specific affinity of associated proteins.

  2. Development and Characterization of A Multiplexed RT-PCR Species Specific Assay for Bovine and one for Porcine Foot-and-Mouth Disease Virus Rule-Out

    SciTech Connect (OSTI)

    Smith, S M; Danganan, L; Tammero, L; Vitalis, B; Lenhoff, R; Naraghi-arani, P; Hindson, B

    2007-08-06

    Lawrence Livermore National Laboratory (LLNL), in collaboration with the Department of Homeland Security (DHS) and the United States Department of Agriculture (USDA), Animal and Plant Health Inspection Services (APHIS) has developed candidate multiplexed assays that may potentially be used within the National Animal Health Laboratory Network (NAHLN), the National Veterinary Services Laboratory (Ames, Iowa) and the Plum Island Animal Disease Center (PIADC). This effort has the ability to improve our nation's capability to discriminate between foreign animal diseases and those that are endemic using a single assay, thereby increasing our ability to protect food and agricultural resources with a diagnostic test which could enhance the nation's capabilities for early detection of a foreign animal disease. In FY2005 with funding from the DHS, LLNL developed the first version (Version 1.0) of a multiplexed (MUX) nucleic-acid-based RT-PCR assay that included signatures for foot-and-mouth disease virus (FMDV) detection with rule-out tests for two other foreign animal diseases (FADs) of swine, Vesicular Exanthema of Swine (VESV) and Swine Vesicular Disease Virus (SVDV), and four other domestic viral diseases Bovine Viral Diarrhea Virus (BVDV), Bovine Herpes Virus 1 (BHV-1), Bluetongue virus (BTV) and Parapox virus complex (which includes Bovine Papular Stomatitis Virus [BPSV], Orf of sheep, and Pseudocowpox). In FY06, LLNL has developed Bovine and Porcine species-specific panel which included existing signatures from Version 1.0 panel as well as new signatures. The MUX RT-PCR porcine assay for detection of FMDV includes the FADs, VESV and SVD in addition to vesicular stomatitis virus (VSV) and porcine reproductive and respiratory syndrome (PRRS). LLNL has also developed a MUX RT-PCR bovine assay for detection of FMDV with rule out tests for the two bovine FADs malignant catarrhal fever (MCF), rinderpest virus (RPV) and the domestic diseases vesicular stomatitis virus (VSV), bovine viral diarrhea virus (BVDV), infectious bovine rhinotracheitus virus (BHV-1), bluetongue virus (BTV), and the Parapox viruses (which are of two bovine types) bovine papular stomatitis virus (BPSV) and psuedocowpox (PCP). A timeline for this development is presented in Table 1. The development of the Version 1.0 panel for FMDV rule-out and the most current efforts aimed to designed species specific panels has spanned over 2 1/2 years with multiple collaborative partnerships. This document provides a summary of the development, testing and performance data at OIE Stage 1 Feasibility into Stage 2 Assay Development and Standardization1 (see Table 2), gathered as of June 30th, 2007 for the porcine and bovine MUX assay panels. We present an overview of the identification and selection of candidate genetic signatures, the assay development process, and preliminary performance data for each of the individual signatures as characterized in the multiplexed format for the porcine and bovine panels. The Stage 1 Feasibility data of the multiplexed panels is presented in this report also includes relevant data acquired from the Version 1.0 panel as supporting information where appropriate. In contrast to last years effort, the development of the bovine and porcine panels is pending additional work to complete analytical characterization of FMDV, VESV, SVD, RPV and MCF. The signature screening process and final panel composition impacts this effort. The unique challenge presented this year was having strict predecessor limitations in completing characterization, where efforts at LLNL must precede efforts at PIADC, such challenges were alleviated in the 2006 reporting by having characterization data from the interlaboratory comparison and at Plum Island under AgDDAP project. We will present an addendum at a later date with additional data on the characterization of the porcine and bovine multiplex assays when that data is available. As a summary report, this document does not provide the details of signature generation, evaluation, and testing, nor does it provide spec

  3. The Chlorella variabilis NC64A Genome Reveals Adaptation to Photosymbiosis, Coevolution with Viruses, and Cryptic Sex

    SciTech Connect (OSTI)

    Blanc, Guillaume; Duncan, Garry A.; Agarakova, Irina; Borodovsky, Mark; Gurnon, James; Kuo, Alan; Lindquist, Erika; Lucas, Susan; Pangailinan, Jasmyn; Polle, Juergen; Salamov, Asaf; Terry, Astrid; Yamada, Takashi; Dunigan, David D.; Grigoriev, Igor V.; Claverie, Jean-Michel; Etten, James L. Van

    2010-05-06

    Chlorella variabilis NC64A, a unicellular photosynthetic green alga (Trebouxiophyceae), is an intracellular photobiont of Paramecium bursaria and a model system for studying virus/algal interactions. We sequenced its 46-Mb nuclear genome, revealing an expansion of protein families that could have participated in adaptation to symbiosis. NC64A exhibits variations in GC content across its genome that correlate with global expression level, average intron size, and codon usage bias. Although Chlorella species have been assumed to be asexual and nonmotile, the NC64A genome encodes all the known meiosis-specific proteins and a subset of proteins found in flagella. We hypothesize that Chlorella might have retained a flagella-derived structure that could be involved in sexual reproduction. Furthermore, a survey of phytohormone pathways in chlorophyte algae identified algal orthologs of Arabidopsis thaliana genes involved in hormone biosynthesis and signaling, suggesting that these functions were established prior to the evolution of land plants. We show that the ability of Chlorella to produce chitinous cell walls likely resulted from the capture of metabolic genes by horizontal gene transfer from algal viruses, prokaryotes, or fungi. Analysis of the NC64A genome substantially advances our understanding of the green lineage evolution, including the genomic interplay with viruses and symbiosis between eukaryotes.

  4. Structure of unliganded HSV gD reveals a mechanism for receptor-mediated activation of virus entry

    SciTech Connect (OSTI)

    Krummenacher, Claude; Supekar, Vinit M.; Whitbeck, J. Charles; Lazear, Eric; Connolly, Sarah A.; Eisenberg, Roselyn J.; Cohen, Gary H.; Wiley, Don C.; Carfi, Andrea

    2010-07-19

    Herpes simplex virus (HSV) entry into cells requires binding of the envelope glycoprotein D (gD) to one of several cell surface receptors. The 50 C-terminal residues of the gD ectodomain are essential for virus entry, but not for receptor binding. We have determined the structure of an unliganded gD molecule that includes these C-terminal residues. The structure reveals that the C-terminus is anchored near the N-terminal region and masks receptor-binding sites. Locking the C-terminus in the position observed in the crystals by an intramolecular disulfide bond abolished receptor binding and virus entry, demonstrating that this region of gD moves upon receptor binding. Similarly, a point mutant that would destabilize the C-terminus structure was nonfunctional for entry, despite increased affinity for receptors. We propose that a controlled displacement of the gD C-terminus upon receptor binding is an essential feature of HSV entry, ensuring the timely activation of membrane fusion.

  5. Molecular basis of endosomal-membrane association for the dengue virus envelope protein

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Rogers, David M.; Kent, Michael S.; Rempe, Susan B.

    2015-01-02

    Dengue virus is coated by an icosahedral shell of 90 envelope protein dimers that convert to trimers at low pH and promote fusion of its membrane with the membrane of the host endosome. We provide the first estimates for the free energy barrier and minimum for two key steps in this process: host membrane bending and protein–membrane binding. Both are studied using complementary membrane elastic, continuum electrostatics and all-atom molecular dynamics simulations. The predicted host membrane bending required to form an initial fusion stalk presents a 22–30 kcal/mol free energy barrier according to a constrained membrane elastic model. Combined continuummore »and molecular dynamics results predict a 15 kcal/mol free energy decrease on binding of each trimer of dengue envelope protein to a membrane with 30% anionic phosphatidylglycerol lipid. The bending cost depends on the preferred curvature of the lipids composing the host membrane leaflets, while the free energy gained for protein binding depends on the surface charge density of the host membrane. The fusion loop of the envelope protein inserts exactly at the level of the interface between the membrane's hydrophobic and head-group regions. As a result, the methods used in this work provide a means for further characterization of the structures and free energies of protein-assisted membrane fusion.« less

  6. Rational design and adaptive management of combination therapies for Hepatitis C virus infection

    SciTech Connect (OSTI)

    Ke, Ruian; Loverdo, Claude; Qi, Hangfei; Sun, Ren; Lloyd-Smith, James O.; Kouyos, Roger Dimitri

    2015-06-30

    Recent discoveries of direct acting antivirals against Hepatitis C virus (HCV) have raised hopes of effective treatment via combination therapies. Yet rapid evolution and high diversity of HCV populations, combined with the reality of suboptimal treatment adherence, make drug resistance a clinical and public health concern. We develop a general model incorporating viral dynamics and pharmacokinetics/ pharmacodynamics to assess how suboptimal adherence affects resistance development and clinical outcomes. We derive design principles and adaptive treatment strategies, identifying a high-risk period when missing doses is particularly risky for de novo resistance, and quantifying the number of additional doses needed to compensate when doses are missed. Using data from large-scale resistance assays, we demonstrate that the risk of resistance can be reduced substantially by applying these principles to a combination therapy of daclatasvir and asunaprevir. By providing a mechanistic framework to link patient characteristics to the risk of resistance, these findings show the potential of rational treatment design.

  7. Molecular basis of endosomal-membrane association for the dengue virus envelope protein

    SciTech Connect (OSTI)

    Rogers, David M.; Kent, Michael S.; Rempe, Susan B.

    2015-01-02

    Dengue virus is coated by an icosahedral shell of 90 envelope protein dimers that convert to trimers at low pH and promote fusion of its membrane with the membrane of the host endosome. We provide the first estimates for the free energy barrier and minimum for two key steps in this process: host membrane bending and protein–membrane binding. Both are studied using complementary membrane elastic, continuum electrostatics and all-atom molecular dynamics simulations. The predicted host membrane bending required to form an initial fusion stalk presents a 22–30 kcal/mol free energy barrier according to a constrained membrane elastic model. Combined continuum and molecular dynamics results predict a 15 kcal/mol free energy decrease on binding of each trimer of dengue envelope protein to a membrane with 30% anionic phosphatidylglycerol lipid. The bending cost depends on the preferred curvature of the lipids composing the host membrane leaflets, while the free energy gained for protein binding depends on the surface charge density of the host membrane. The fusion loop of the envelope protein inserts exactly at the level of the interface between the membrane's hydrophobic and head-group regions. As a result, the methods used in this work provide a means for further characterization of the structures and free energies of protein-assisted membrane fusion.

  8. Primary Radiation Therapy for Head-and-Neck Cancer in the Setting of Human Immunodeficiency Virus

    SciTech Connect (OSTI)

    Klein, Emily A.; Guiou, Michael; Farwell, D. Gregory; Luu, Quang; Lau, Derick H.; Stuart, Kerri; Vaughan, Andrew; Vijayakumar, Srinivasan; Chen, Allen M.

    2011-01-01

    Purpose: To analyze outcomes after radiation therapy for head-and-neck cancer among a cohort of patients with human immunodeficiency virus (HIV). Methods and Materials: The medical records of 12 patients with serologic evidence of HIV who subsequently underwent radiation therapy to a median dose of 68 Gy (range, 64-72 Gy) for newly diagnosed squamous cell carcinoma of the head and neck were reviewed. Six patients (50%) received concurrent chemotherapy. Intensity-modulated radiotherapy was used in 6 cases (50%). All patients had a Karnofsky performance status of 80 or 90. Nine patients (75%) were receiving antiretroviral therapies at the time of treatment, and the median CD4 count was 460 (range, 266-800). Toxicity was graded according to the Radiation Therapy Oncology Group / European Organization for the Treatment of Cancer toxicity criteria. Results: The 3-year estimates of overall survival and local-regional control were 78% and 92%, respectively. Acute Grade 3+ toxicity occurred in 7 patients (58%), the most common being confluent mucositis (5 patients) and moist skin desquamation (4 patients). Two patients experienced greater than 10% weight loss, and none experienced more than 15% weight loss from baseline. Five patients (42%) experienced treatment breaks in excess of 10 cumulative days, although none required hospitalization. There were no treatment-related fatalities. Conclusions: Radiation therapy for head-and-neck cancer seems to be relatively well tolerated among appropriately selected patients with HIV. The observed rates of toxicity were comparable to historical controls without HIV.

  9. Human immunodeficiency virus contains an epitope immunoreactive with thymosin. cap alpha. /sub 1/ and the 30-amino acid synthetic p17 group-specific antigen peptide HGP-30

    SciTech Connect (OSTI)

    Naylor, P.H.; Naylor, C.W.; Badamchian, M.; Wada, S.; Goldstein, A.L.; Wang, S.S.; Sun, D.K.; Thornton, A.H.; Sarin, P.S.

    1987-05-01

    The authors have reported that an antiserum prepared against thymosin ..cap alpha../sub 1/ (which shares a region of homology with the p17 protein of the acquired immunodeficiency syndrome (AIDS)-associated human immunodeficiency virus) effectively neutralized the AIDs virus and prevented its replication in H9 cells. Using HPLC and immunoblot analysis, they have identified from a clone B, type III human T-lymphotropic virus (HTLV-IIIB) extracts a protein with a molecular weight of 17,000 that is immunoreactive with thymosin ..cap alpha../sub 1/. In contrast, no immunoreactivity was found in retroviral extracts from a number of nonhuman species including feline, bovine, simian, gibbon, and murine retroviruses. Heterologous antiserum prepared against a 30-amino acid synthetic peptide analogue (HGP-30) does not cross-react with thymosin ..cap alpha../sub 1/ but does react specifically with the p17 protein of the AIDS virus in a manner identical to that seen with an HTLV-IIIB p17-specific monoclonal antibody. The demonstration that this synthetic analogue is immunogenic and that antibodies to HGP-30 cross-react not only with synthetic peptide but also with the HTLV-IIIB p17 viral protein provides an additional, and potentially more specific, candidate for development of a synthetic peptide vaccine for AIDS. In addition, the p17 synthetic peptide (HGP-3) may prove to be useful in a diagnostic assay for the detection of AIDS virus infection in seronegative individuals.

  10. Inhibition of hepatitis B virus (HBV) by LNA-mediated nuclear interference with HBV DNA transcription

    SciTech Connect (OSTI)

    Sun, Zhen; Department of Biochemistry and Molecular Biology, Program in Molecular Cell Biology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058 ; Xiang, Wenqing; Guo, Yajuan; Chen, Zhi; Liu, Wei; Lu, Daru

    2011-06-10

    Highlights: {yields} LNA-modified oligonucleotides can pass through the plasma membrane of cultured cells even without using transfection machinery. {yields} LNA-modified oligonucleotides passed efficiently across the cell membrane, and lipid-coating facilitated translocation from the cytoplasm to the nucleus. {yields} LNA-oligonucleotide designed to target nuclear HBV DNA efficiently suppresses HBV replication and transcription in cultured hepatic cells. -- Abstract: Silencing target genes with small regulatory RNAs is widely used to investigate gene function and therapeutic drug development. Recently, triplex-based approaches have provided another attractive means to achieve targeted gene regulation and gene manipulation at the molecular and cellular levels. Nuclear entry of oligonucleotides and enhancement of their affinity to the DNA targets are key points of such approaches. In this study, we developed lipid-based transport of a locked-nucleic-acid (LNA)-modified oligonucleotide for hepatitis B virus (HBV) DNA interference in human hepatocytes expressing HBV genomic DNA. In these cells, the LNA-modified oligonucleotides passed efficiently across the cell membrane, and lipid-coating facilitated translocation from the cytoplasm to the nucleus. The oligonucleotide specifically targeting HBV DNA clearly interfered with HBV DNA transcription as shown by a block in pregenomic RNA (pgRNA) production. The HBV DNA-targeted oligonucleotide suppressed HBV DNA replication and HBV protein production more efficiently than small interfering RNAs directed to the pgRNA. These results demonstrate that fusion with lipid can carry LNA-modified oligonucleotides to the nucleus where they regulate gene expression. Interfering with HBV DNA transcription by LNA-modified oligonucleotides has strong potential as a new strategy for HBV inhibition.

  11. Both core and F proteins of hepatitis C virus could enhance cell proliferation in transgenic mice

    SciTech Connect (OSTI)

    Hu, Wen-Ta; Li, Hui-Chun; Lee, Shen-Kao; Ma, Hsin-Chieh; Yang, Chee-Hing; Chen, Hung-Ling; Lo, Shih-Yen; Department of Laboratory Medicine, Buddhist Tzu Chi General Hospital, Hualien, Taiwan

    2013-05-24

    Highlights: •HCV core and F proteins could induce hepatocyte proliferation in the transgenic mice. •?-Catenin signaling pathway was activated by core protein in the transgenic mice. •?-Catenin signaling pathway was activated by myc-F protein in the transgenic mice. •Expression of SMA protein was enhanced by core but not myc-F protein. -- Abstract: The role of the protein encoded by the alternative open reading frame (ARF/F/core+1) of the Hepatitis C virus (HCV) genome in viral pathogenesis remains unknown. The different forms of ARF/F/core+1 protein were labile in cultured cells, a myc-tag fused at the N-terminus of the F protein made it more stable. To determine the role of core and F proteins in HCV pathogenesis, transgenic mice with either protein expression under the control of Albumin promoter were generated. Expression of core protein and F protein with myc tag (myc-F) could be detected by Western blotting analysis in the livers of these mice. The ratio of liver to body weight is increased for both core and myc-F transgenic mice compared to that of wild type mice. Indeed, the proliferating cell nuclear antigen protein, a proliferation marker, was up-regulated in the transgenic mice with core or myc-F protein. Further analyses by microarray and Western blotting suggested that ?-catenin signaling pathway was activated by either core or myc-F protein in the transgenic mice. These transgenic mice were further treated with either Diethynitrosamine (a tumor initiator) or Phenobarbital (a tumor promoter). Phenobarbital but not Diethynitrosamine treatment could increase the liver/body weight ratio of these mice. However, no tumor formation was observed in these mice. In conclusion, HCV core and myc-F proteins could induce hepatocyte proliferation in the transgenic mice possibly through ?-catenin signaling pathway.

  12. Binding of undamaged double stranded DNA to vaccinia virus uracil-DNA glycosylase

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Schormann, Norbert; Banerjee, Surajit; Ricciardi, Robert; Chattopadhyay, Debasish

    2015-06-02

    Background: Uracil-DNA glycosylases are evolutionarily conserved DNA repair enzymes. However, vaccinia virus uracil-DNA glycosylase (known as D4), also serves as an intrinsic and essential component of the processive DNA polymerase complex during DNA replication. In this complex D4 binds to a unique poxvirus specific protein A20 which tethers it to the DNA polymerase. At the replication fork the DNA scanning and repair function of D4 is coupled with DNA replication. So far, DNA-binding to D4 has not been structurally characterized. Results: This manuscript describes the first structure of a DNA-complex of a uracil-DNA glycosylase from the poxvirus family. This alsomore » represents the first structure of a uracil DNA glycosylase in complex with an undamaged DNA. In the asymmetric unit two D4 subunits bind simultaneously to complementary strands of the DNA double helix. Each D4 subunit interacts mainly with the central region of one strand. DNA binds to the opposite side of the A20-binding surface on D4. In comparison of the present structure with the structure of uracil-containing DNA-bound human uracil-DNA glycosylase suggests that for DNA binding and uracil removal D4 employs a unique set of residues and motifs that are highly conserved within the poxvirus family but different in other organisms. Conclusion: The first structure of D4 bound to a truly non-specific undamaged double-stranded DNA suggests that initial binding of DNA may involve multiple non-specific interactions between the protein and the phosphate backbone.« less

  13. The Role of a Host Protein (TIP) in the Resistance Response of Arabidopsis to Turnip Crinkle Virus Infection.

    SciTech Connect (OSTI)

    T. Jack Morris, School of Biological Sciences, University of Nebraska, Lincoln, NE 68588-0118

    2008-10-20

    Our research on Turnip crinkle virus (TCV) has shown that the viral capsid protein (CP) is both a virulence factor as well as the elicitor of a hypersensitive resistance response (HR) to the virus in Arabidopsis. Initially, we identified a protein from Arabidopsis that specifically interacted with the viral CP using a yeast two-hybrid screen. This protein, designated TIP for TCV-Interacting Protein, is a member of the NAC family of plant transcription factors implicated in the regulation of development and senescence. When TCV CP was mutated to eliminate its ability to interact with TIP, the corresponding virus mutants broke the HR-mediated resistance conferred by the HRT resistance (R) gene in Arabidopsis ecotype Dijon (Di)-17. This result suggested that TIP is a component of the signal transduction pathway that leads to the genetically specified TCV resistance. We next confirmed that TIP and the viral CP interact in plant cells and that this interaction prevents nuclear localization of this transcription factor. We demonstrated that TCV CP suppresses post-transcriptional gene silencing (PTGS), a newly discovered RNA-mediated defense system in plants. Together these results suggest that the CP is a virulence factor that could well be functioning through its interaction with TIP. We have proposed a model involving the role of TIP and CP in triggering HR mediated plant defense that fits with the current thinking about how gene-for-gene resistance may function. A unique component of our system is the opportunity to link R-gene function with the newly discovered RNA silencing pathway that is not only a potent defense against viral pathogens, but also regulates early development in plants. In the current funding period we made several significant findings: First, we completed an array analysis comparing gene expression in Arabidopsis infected with TCV and a mutant virus unable to bind TIP. Second, we produced transgenic lines that over-express and inducibly under-express TIP. These accomplishments now form the basis for our continued effort towards providing a complete understanding of molecular events leading to susceptible and resistant interactions between TCV and Arabidopsis plants. Our data strongly suggest that TIP is involved in activating the SA-mediated defense pathway and that TCV CP acts to repress this role of TIP.

  14. Release of the herpes simplex virus 1 protease by self cleavage is required for proper conformation of the portal vertex

    SciTech Connect (OSTI)

    Yang, Kui; Wills, Elizabeth G.; Baines, Joel D.

    2012-07-20

    We identify an NLS within herpes simplex virus scaffold proteins that is required for optimal nuclear import of these proteins into infected or uninfected nuclei, and is sufficient to mediate nuclear import of GFP. A virus lacking this NLS replicated to titers reduced by 1000-fold, but was able to make capsids containing both scaffold and portal proteins suggesting that other functions can complement the NLS in infected cells. We also show that Vp22a, the major scaffold protein, is sufficient to mediate the incorporation of portal protein into capsids, whereas proper portal immunoreactivity in the capsid requires the larger scaffold protein pU{sub L}26. Finally, capsid angularization in infected cells did not require the HSV-1 protease unless full length pU{sub L}26 was expressed. These data suggest that the HSV-1 portal undergoes conformational changes during capsid maturation, and reveal that full length pU{sub L}26 is required for this conformational change.

  15. Activation/proliferation and apoptosis of bystander goat lymphocytes induced by a macrophage-tropic chimeric caprine arthritis encephalitis virus expressing SIV Nef

    SciTech Connect (OSTI)

    Bouzar, Baya Amel; Rea, Angela; Hoc-Villet, Stephanie; Garnier, Celine; Guiguen, Francois; Jin Yuhuai; Narayan, Opendra; Chebloune, Yahia . E-mail: ychebloune@kumc.edu

    2007-08-01

    Caprine arthritis encephalitis virus (CAEV) is the natural lentivirus of goats, well known for its tropism for macrophages and its inability to cause infection in lymphocytes. The viral genome lacks nef, tat, vpu and vpx coding sequences. To test the hypothesis that when nef is expressed by the viral genome, the virus became toxic for lymphocytes during replication in macrophages, we inserted the SIVsmm PBj14 nef coding sequences into the genome of CAEV thereby generating CAEV-nef. This recombinant virus is not infectious for lymphocytes but is fully replication competent in goat macrophages in which it constitutively expresses the SIV Nef. We found that goat lymphocytes cocultured with CAEV-nef-infected macrophages became activated, showing increased expression of the interleukin-2 receptor (IL-2R). Activation correlated with increased proliferation of the cells. Interestingly, a dual effect in terms of apoptosis regulation was observed in exposed goat lymphocytes. Nef was found first to induce a protection of lymphocytes from apoptosis during the first few days following exposure to infected macrophages, but later it induced increased apoptosis in the activated lymphocytes. This new recombinant virus provides a model to study the functions of Nef in the context of infection of macrophages, but in absence of infection of T lymphocytes and brings new insights into the biological effects of Nef on lymphocytes.

  16. A human monoclonal antibody derived from a vaccinated volunteer recognizes heterosubtypically a novel epitope on the hemagglutinin globular head of H1 and H9 influenza A viruses

    SciTech Connect (OSTI)

    Boonsathorn, Naphatsawan; Panthong, Sumolrat; Chittaganpitch, Malinee; Phuygun, Siripaporn; Waicharoen, Sunthareeya; Prachasupap, Apichai; Yasugi, Mayo; Ono, Ken-ichiro; and others

    2014-09-26

    Highlights: • A human monoclonal antibody against influenza virus was produced from a volunteer. • The antibody was generated from the PBMCs of the volunteer using the fusion method. • The antibody neutralized heterosubtypically group 1 influenza A viruses (H1 and H9). • The antibody targeted a novel epitope in globular head region of the hemagglutinin. • Sequences of the identified epitope are highly conserved among H1 and H9 subtypes. - Abstract: Most neutralizing antibodies elicited during influenza virus infection or by vaccination have a narrow spectrum because they usually target variable epitopes in the globular head region of hemagglutinin (HA). In this study, we describe a human monoclonal antibody (HuMAb), 5D7, that was prepared from the peripheral blood lymphocytes of a vaccinated volunteer using the fusion method. The HuMAb heterosubtypically neutralizes group 1 influenza A viruses, including seasonal H1N1, 2009 pandemic H1N1 (H1N1pdm) and avian H9N2, with a strong hemagglutinin inhibition activity. Selection of an escape mutant showed that the HuMAb targets a novel conformational epitope that is located in the HA head region but is distinct from the receptor binding site. Furthermore, Phe114Ile substitution in the epitope made the HA unrecognizable by the HuMAb. Amino acid residues in the predicted epitope region are also highly conserved in the HAs of H1N1 and H9N2. The HuMAb reported here may be a potential candidate for the development of therapeutic/prophylactic antibodies against H1 and H9 influenza viruses.

  17. An intrinsically disordered peptide from Ebola virus VP35 controls viral RNA synthesis by modulating nucleoprotein-RNA interactions

    SciTech Connect (OSTI)

    Leung, Daisy  W.; Borek, Dominika; Luthra, Priya; Binning, Jennifer  M.; Anantpadma, Manu; Liu, Gai; Harvey, Ian B.; Su, Zhaoming; Endlich-Frazier, Ariel; Pan, Juanli; Shabman, Reed  S.; Chiu, Wah; Davey, Robert  A.; Otwinowski, Zbyszek; Basler, Christopher  F.; Amarasinghe, Gaya  K.

    2015-04-01

    During viral RNA synthesis, Ebola virus (EBOV) nucleoprotein (NP) alternates between an RNA-template-bound form and a template-free form to provide the viral polymerase access to the RNA template. In addition, newly synthesized NP must be prevented from indiscriminately binding to noncognate RNAs. Here, we investigate the molecular bases for these critical processes. We identify an intrinsically disordered peptide derived from EBOV VP35 (NPBP, residues 20–48) that binds NP with high affinity and specificity, inhibits NP oligomerization, and releases RNA from NP-RNA complexes in vitro. The structure of the NPBP/ΔNPNTD complex, solved to 3.7 Å resolution, reveals how NPBP peptide occludes a large surface area that is important for NP-NP and NP-RNA interactions and for viral RNA synthesis. Together, our results identify a highly conserved viral interface that is important for EBOV replication and can be targeted for therapeutic development.

  18. Human non-neutralizing HIV-1 envelope monoclonal antibodies limit the number of founder viruses during SHIV mucosal infection in rhesus macaques

    SciTech Connect (OSTI)

    Santra, Sampa; Tomaras, Georgia D.; Warrier, Ranjit; Nicely, Nathan I.; Liao, Hua -Xin; Pollara, Justin; Liu, Pinghuang; Alam, S. Munir; Zhang, Ruijun; Cocklin, Sarah L.; Shen, Xiaoying; Duffy, Ryan; Xia, Shi -Mao; Schutte, Robert J.; Pemble IV, Charles W.; Dennison, S. Moses; Li, Hui; Chao, Andrew; Vidnovic, Kora; Evans, Abbey; Klein, Katja; Kumar, Amit; Robinson, James; Landucci, Gary; Forthal, Donald N.; Montefiori, David C.; Kaewkungwal, Jaranit; Nitayaphan, Sorachai; Pitisuttithum, Punnee; Rerks-Ngarm, Supachai; Robb, Merlin L.; Michael, Nelson L.; Kim, Jerome H.; Soderberg, Kelly A.; Giorgi, Elena E.; Blair, Lily; Korber, Bette T.; Moog, Christiane; Shattock, Robin J.; Letvin, Norman L.; Schmitz, Joern E.; Moody, M. A.; Gao, Feng; Ferrari, Guido; Shaw, George M.; Haynes, Barton F.; Douek, Daniel C.

    2015-08-03

    HIV-1 mucosal transmission begins with virus or virus-infected cells moving through mucus across mucosal epithelium to infect CD4? T cells. Although broadly neutralizing antibodies (bnAbs) are the type of HIV-1 antibodies that are most likely protective, they are not induced with current vaccine candidates. In contrast, antibodies that do not neutralize primary HIV-1 strains in the TZM-bl infection assay are readily induced by current vaccine candidates and have also been implicated as secondary correlates of decreased HIV-1 risk in the RV144 vaccine efficacy trial. Here, we have studied the capacity of anti-Env monoclonal antibodies (mAbs) against either the immunodominant region of gp41 (7B2 IgG1), the first constant region of gp120 (A32 IgG1), or the third variable loop (V3) of gp120 (CH22 IgG1) to modulate in vivo rectal mucosal transmission of a high-dose simian-human immunodeficiency virus (SHIV-BaL) in rhesus macaques. 7B2 IgG1 or A32 IgG1, each containing mutations to enhance Fc function, was administered passively to rhesus macaques but afforded no protection against productive clinical infection while the positive control antibody CH22 IgG1 prevented infection in 4 of 6 animals. Enumeration of transmitted/founder (T/F) viruses revealed that passive infusion of each of the three antibodies significantly reduced the number of T/F genomes. Some antibodies that bind HIV-1 Env but fail to neutralize virus in traditional neutralization assays may limit the number of T/F viruses involved in transmission without leading to enhancement of viral infection. For one of these mAbs, gp41 mAb 7B2, we provide the first co-crystal structure in complex with a common cyclical loop motif demonstrated to be critical for infection by other retroviruses.

  19. Human non-neutralizing HIV-1 envelope monoclonal antibodies limit the number of founder viruses during SHIV mucosal infection in rhesus macaques

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Santra, Sampa; Tomaras, Georgia D.; Warrier, Ranjit; Nicely, Nathan I.; Liao, Hua -Xin; Pollara, Justin; Liu, Pinghuang; Alam, S. Munir; Zhang, Ruijun; Cocklin, Sarah L.; et al

    2015-08-03

    HIV-1 mucosal transmission begins with virus or virus-infected cells moving through mucus across mucosal epithelium to infect CD4âș T cells. Although broadly neutralizing antibodies (bnAbs) are the type of HIV-1 antibodies that are most likely protective, they are not induced with current vaccine candidates. In contrast, antibodies that do not neutralize primary HIV-1 strains in the TZM-bl infection assay are readily induced by current vaccine candidates and have also been implicated as secondary correlates of decreased HIV-1 risk in the RV144 vaccine efficacy trial. Here, we have studied the capacity of anti-Env monoclonal antibodies (mAbs) against either the immunodominant regionmore » of gp41 (7B2 IgG1), the first constant region of gp120 (A32 IgG1), or the third variable loop (V3) of gp120 (CH22 IgG1) to modulate in vivo rectal mucosal transmission of a high-dose simian-human immunodeficiency virus (SHIV-BaL) in rhesus macaques. 7B2 IgG1 or A32 IgG1, each containing mutations to enhance Fc function, was administered passively to rhesus macaques but afforded no protection against productive clinical infection while the positive control antibody CH22 IgG1 prevented infection in 4 of 6 animals. Enumeration of transmitted/founder (T/F) viruses revealed that passive infusion of each of the three antibodies significantly reduced the number of T/F genomes. Some antibodies that bind HIV-1 Env but fail to neutralize virus in traditional neutralization assays may limit the number of T/F viruses involved in transmission without leading to enhancement of viral infection. For one of these mAbs, gp41 mAb 7B2, we provide the first co-crystal structure in complex with a common cyclical loop motif demonstrated to be critical for infection by other retroviruses.« less

  20. Structure of the vesicular stomatitis virus nucleocapsid in complex with the nucleocapsid-binding domain of the small polymerase cofactor, P

    SciTech Connect (OSTI)

    Green, Todd J.; Luo, Ming

    2009-10-05

    The negative-strand RNA viruses (NSRVs) are unique because their nucleocapsid, not the naked RNA, is the active template for transcription and replication. The viral polymerase of nonsegmented NSRVs contains a large polymerase catalytic subunit (L) and a nonenzymatic cofactor, the phosphoprotein (P). Insight into how P delivers the polymerase complex to the nucleocapsid has long been pursued by reverse genetics and biochemical approaches. Here, we present the X-ray crystal structure of the C-terminal domain of P of vesicular stomatitis virus, a prototypic nonsegmented NSRV, bound to nucleocapsid-like particles. P binds primarily to the C-terminal lobe of 2 adjacent N proteins within the nucleocapsid. This binding mode is exclusive to the nucleocapsid, not the nucleocapsid (N) protein in other existing forms. Localization of phosphorylation sites within P and their proximity to the RNA cavity give insight into how the L protein might be oriented to access the RNA template.

  1. Development and Characterization of a Multiplexed RT-PCR Species Specific Assay for Bovine and one for Porcine Foot-and-Mouth Disease Virus Rule-Out Supplemental Materials

    SciTech Connect (OSTI)

    Smith, S; Danganan, L; Tammero, L; Lenhoff, R; Naraghi-arani, P; Hindson, B

    2007-08-06

    Lawrence Livermore National Laboratory (LLNL), in collaboration with the Department of Homeland Security (DHS) and the United States Department of Agriculture (USDA), Animal and Plant Health Inspection Services (APHIS) has developed advanced rapid diagnostics that may be used within the National Animal Health Laboratory Network (NAHLN), the National Veterinary Services Laboratory (Ames, Iowa) and the Plum Island Animal Disease Center (PIADC). This effort has the potential to improve our nation's ability to discriminate between foreign animal diseases and those that are endemic using a single assay, thereby increasing our ability to protect animal populations of high economic importance in the United States. Under 2005 DHS funding we have developed multiplexed (MUX) nucleic-acid-based PCR assays that combine foot-and-mouth disease virus (FMDV) detection with rule-out tests for two other foreign animal diseases Vesicular Exanthema of Swine (VESV) and Swine Vesicular Disease (SVD) and four other domestic viral diseases Bovine Viral Diarrhea Virus (BVDV), Bovine Herpes Virus 1 (BHV-1 or Infectious Bovine Rhinotracheitus IBR), Bluetongue virus (BTV) and Parapox virus complex (which includes Bovine Papular Stomatitis Virus BPSV, Orf of sheep, and Pseudocowpox). Under 2006 funding we have developed a Multiplexed PCR [MUX] porcine assay for detection of FMDV with rule out tests for VESV and SVD foreign animal diseases in addition to one other domestic vesicular animal disease vesicular stomatitis virus (VSV) and one domestic animal disease of swine porcine reproductive and respiratory syndrome (PRRS). We have also developed a MUX bovine assay for detection of FMDV with rule out tests for the two bovine foreign animal diseases malignant catarrhal fever (MCF), rinderpest virus (RPV) and the domestic diseases vesicular stomatitis virus (VSV), bovine viral diarrhea virus (BVDV), infectious bovine rhinotracheitus virus (BHV-1), bluetongue virus (BTV), and the Parapox viruses which are of two bovine types bovine papular stomatitis virus (BPSV) and psuedocowpox (PCP). This document provides details of signature generation, evaluation, and testing, as well as the specific methods and materials used. A condensed summary of the development, testing and performance of the multiplexed assay panel was presented in a 126 page separate document, entitled 'Development and Characterization of A Multiplexed RT-PCR Species Specific Assay for Bovine and one for Porcine Foot-and-Mouth Disease Virus Rule-Out'. This supplemental document provides additional details of large amount of data collected for signature generation, evaluation, and testing, as well as the specific methods and materials used for all steps in the assay development and utilization processes. In contrast to last years effort, the development of the bovine and porcine panels is pending additional work to complete analytical characterization of FMDV, VESV, VSV, SVD, RPV and MCF. The signature screening process and final panel composition impacts this effort. The unique challenge presented this year was having strict predecessor limitations in completing characterization, where efforts at LLNL must preceed efforts at PIADC, such challenges were alleviated in the 2006 reporting by having characterization data from the interlaboratory comparison and at Plum Island under AgDDAP project. We will present an addendum at a later date with additional data on the characterization of the porcine and bovine multiplex assays when that data is available.

  2. Palmitoylation of the feline immunodeficiency virus envelope glycoprotein and its effect on fusion activity and envelope incorporation into virions

    SciTech Connect (OSTI)

    Gonzalez, Silvia A.; Paladino, Monica G.; Affranchino, Jose L.

    2012-06-20

    The feline immunodeficiency virus (FIV) envelope glycoprotein (Env) possesses a short cytoplasmic domain of 53 amino acids containing four highly conserved cysteines at Env positions 804, 811, 815 and 848. Since palmitoylation of transmembrane proteins occurs at or near the membrane anchor, we investigated whether cysteines 804, 811 and 815 are acylated and analyzed the relevance of these residues for Env functions. Replacement of cysteines 804, 811 and 815 individually or in combination by serine residues resulted in Env glycoproteins that were efficiently expressed and processed. However, mutations C804S and C811S reduced Env fusogenicity by 93% and 84%, respectively, compared with wild-type Env. By contrast, mutant C815S exhibited a fusogenic capacity representing 50% of the wild-type value. Remarkably, the double mutation C804S/C811S abrogated both Env fusion activity and Env incorporation into virions. Finally, by means of Click chemistry assays we demonstrated that the four FIV Env cytoplasmic cysteines are palmitoylated.

  3. An intrinsically disordered peptide from Ebola virus VP35 controls viral RNA synthesis by modulating nucleoprotein-RNA interactions

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Leung, Daisy  W.; Borek, Dominika; Luthra, Priya; Binning, Jennifer  M.; Anantpadma, Manu; Liu, Gai; Harvey, Ian B.; Su, Zhaoming; Endlich-Frazier, Ariel; Pan, Juanli; et al

    2015-04-01

    During viral RNA synthesis, Ebola virus (EBOV) nucleoprotein (NP) alternates between an RNA-template-bound form and a template-free form to provide the viral polymerase access to the RNA template. In addition, newly synthesized NP must be prevented from indiscriminately binding to noncognate RNAs. Here, we investigate the molecular bases for these critical processes. We identify an intrinsically disordered peptide derived from EBOV VP35 (NPBP, residues 20–48) that binds NP with high affinity and specificity, inhibits NP oligomerization, and releases RNA from NP-RNA complexes in vitro. The structure of the NPBP/ΔNPNTD complex, solved to 3.7 Å resolution, reveals how NPBP peptide occludesmore » a large surface area that is important for NP-NP and NP-RNA interactions and for viral RNA synthesis. Together, our results identify a highly conserved viral interface that is important for EBOV replication and can be targeted for therapeutic development.« less

  4. Role for a region of helically unstable DNA within the Epstein-Barr virus latent cycle origin of DNA replication oriP in origin function

    SciTech Connect (OSTI)

    Polonskaya, Zhanna; Benham, Craig J.; Hearing, Janet . E-mail: jhearing@ms.cc.sunysb.edu

    2004-10-25

    The minimal replicator of the Epstein-Barr virus (EBV) latent cycle origin of DNA replication oriP is composed of two binding sites for the Epstein-Barr virus nuclear antigen-1 (EBNA-1) and flanking inverted repeats that bind the telomere repeat binding factor TRF2. Although not required for minimal replicator activity, additional binding sites for EBNA-1 and TRF2 and one or more auxiliary elements located to the right of the EBNA-1/TRF2 sites are required for the efficient replication of oriP plasmids. Another region of oriP that is predicted to be destabilized by DNA supercoiling is shown here to be an important functional component of oriP. The ability of DNA fragments of unrelated sequence and possessing supercoiled-induced DNA duplex destabilized (SIDD) structures, but not fragments characterized by helically stable DNA, to substitute for this component of oriP demonstrates a role for the SIDD region in the initiation of oriP-plasmid DNA replication.

  5. In vivo subcellular localization of Mal de Rio Cuarto virus (MRCV) non-structural proteins in insect cells reveals their putative functions

    SciTech Connect (OSTI)

    Maroniche, Guillermo A.; Mongelli, Vanesa C.; Llauger, Gabriela; Alfonso, Victoria; Taboga, Oscar

    2012-09-01

    The in vivo subcellular localization of Mal de Rio Cuarto virus (MRCV, Fijivirus, Reoviridae) non-structural proteins fused to GFP was analyzed by confocal microscopy. P5-1 showed a cytoplasmic vesicular-like distribution that was lost upon deleting its PDZ binding TKF motif, suggesting that P5-1 interacts with cellular PDZ proteins. P5-2 located at the nucleus and its nuclear import was affected by the deletion of its basic C-termini. P7-1 and P7-2 also entered the nucleus and therefore, along with P5-2, could function as regulators of host gene expression. P6 located in the cytoplasm and in perinuclear cloud-like inclusions, was driven to P9-1 viroplasm-like structures and co-localized with P7-2, P10 and {alpha}-tubulin, suggesting its involvement in viroplasm formation and viral intracellular movement. Finally, P9-2 was N-glycosylated and located at the plasma membrane in association with filopodia-like protrusions containing actin, suggesting a possible role in virus cell-to-cell movement and spread.

  6. Joint environmental assessment 1997--2001 of the California Department of Food and Agriculture Curly Top Virus Control Program for Bureau of Land Management and Department of Energy

    SciTech Connect (OSTI)

    1997-03-01

    The DOE, Naval Petroleum reserves in California (NPRC), proposes to sign an Amendment to the Cooperative Agreement and Supplement with the California Department of Food and Agriculture (CDFA) to extend the term of the Curly Top Virus Control Program (CTVCP) in California. This program involves Malathion spraying on NPRC lands to control the beet leafhopper, over a five year period from 1997 through 2001. It is expected that approximately 330 acres on Naval Petroleum Reserve Number 1 (NPR-1) and approximately 9,603 acres on Naval Petroleum Reserve Number 2 (NPR-2) will be treated with Malathion annually by CDFA during the course of this program. The actual acreage subject to treatment can vary from year to year. Pursuant to the requirements of the National Environmental Policy Act of 1969 (NEPA), as amended, the potential impacts of the proposed action were analyzed in a Joint Environmental Assessment (DOE/EA-1011) with the US Department of Interior, Bureau of Land Management (BLM) acting as lead agency, in consultation with the CDFA, and the DOE acting as a cooperating agency. Based on the analysis in the EA, DOE has determined that the conduct of the Curly Top Virus Control Program in California is not a major Federal action significantly affecting the quality of the human environment, within the meaning of the NEPA. Therefore, the preparation of an Environmental Impact Statement is not required and DOE is consequently issuing a FONSI.

  7. Overexpression of the human BCL-2 gene product results in growth enhancement of Epstein-Barr virus-immortalized B cells

    SciTech Connect (OSTI)

    Tsujimoto, Yoshihide (Wistar Institute of Anatomy and Biology, Philadelphia, PA (USA))

    1989-03-01

    The biological activity of the human BCL-2 gene product was analyzed in an Epstein-Barr virus (EBV)-infected human lymphoblastoid B-cell line transfected with BCL-2 sequences driven by the simian virus 40 promoter and enhancer. Overproduction of the BCL-2 protein conferred a selective growth advantage to the EBV-infected B cells as compared with control transfectants in low-serum medium and also after seeding at limiting dilution but did not render the cells tumorigenic in athymic nude mice. This growth enhancement was also seen in cells transfected with the BCL-2 gene with its own promoter juxtaposed to the immunoglobulin heavy chain gene enhancer, which represents the translocated form of the BCL-2 gene observed in follicular lymphomas with the t(14;18) translocation. The growth advantage of EBV-infected B cells overproducing the BCL-2 protein is neither due to the enhanced growth factor production nor due to an enhanced sensitivity of the BCL-2 transfectants to interleukins 1 or 6, although both lymphokines are known to stimulate proliferation of EBV-infected B-cell lines. The growth advantage of EBV-infected B-cell lines. The growth advantage of EBV-infected B cells by overproduction of the BCL-2 protein suggests the direct involvement of the BCL-2 gene product in the pathogenesis of follicular lymphoma.

  8. News Item

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Outsmarting Thermodynamics in Self-assembly of Nanostructures If you can uniformly break the symmetry of nanorod pairs in a colloidal solution, you're one step closer to achieving new and exciting metamaterial properties. The development of an innovative self-assembly route could surpass the conventional thermodynamic limit in chemical synthetic systems and lead to the production of nanostructures that have historically been considered impossible to assemble. But traditional thermodynamic-driven

  9. Molecular Foundry

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    NEWS ARCHIVE < News and Highlights Research Performed by Foundry Industrial Users Honored by Nanotechnology Journal User work on printable photonics was selected as a Highlight of the Year by Nanotechnology in the area of "patterning and nano fabrication". [MORE] Outsmarting Thermodynamics in Self-assembly of Nanostructures Foundry user - and Materials Sciences Division Director - reports method for symmetry-breaking in feedback-driven self-assembly of optical metamaterials. [MORE]

  10. NREL: Photovoltaics Research - News Release Archives

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    2 December 28, 2012 Award-Winning PV Cell Pushes Efficiency Higher NREL and Solar Junction outsmart the solar spectrum and set a world record with a 44%-efficient solar cell. December 4, 2012 NREL Teams with Berkeley Lab to Analyze Solar Pricing Trends and Benchmark "Soft" Costs for PV Systems The U.S. Department of Energy's (DOE)'s National Renewable Energy Laboratory (NREL) and Lawrence Berkeley National Laboratory (LBL) jointly released two reports examining solar photovoltaic (PV)

  11. NREL: Solar Research - News Release Archives

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    2 December 28, 2012 Award-Winning PV Cell Pushes Efficiency Higher NREL and Solar Junction outsmart the solar spectrum and set a world record with a 44%-efficient solar cell. December 4, 2012 NREL Teams with Berkeley Lab to Analyze Solar Pricing Trends and Benchmark "Soft" Costs for PV Systems The U.S. Department of Energy's (DOE)'s National Renewable Energy Laboratory (NREL) and Lawrence Berkeley National Laboratory (LBL) jointly released two reports examining solar photovoltaic (PV)

  12. NREL: Technology Transfer - News Release Archives

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    2 October 25, 2012 NREL's Industry Growth Forum The U.S. Department of Energy's National Renewable Energy Laboratory (NREL) 25th Industry Growth Forum this week attracted nearly 400 investors, entrepreneurs, scientists and policymakers to Denver. December 28, 2012 Award-Winning PV Cell Pushes Efficiency Higher NREL and Solar Junction outsmart the solar spectrum and set a world record with a 44%-efficient solar cell. December 20, 2012 Concentrated Solar Power with Thermal Energy Storage Can Help

  13. Non-destructive observation of intact bacteria and viruses in water by the highly sensitive frequency transmission electric-field method based on SEM

    SciTech Connect (OSTI)

    Ogura, Toshihiko

    2014-08-08

    Highlights: • We developed a high-sensitive frequency transmission electric-field (FTE) system. • The output signal was highly enhanced by applying voltage to a metal layer on SiN. • The spatial resolution of new FTE method is 41 nm. • New FTE system enables observation of the intact bacteria and virus in water. - Abstract: The high-resolution structural analysis of biological specimens by scanning electron microscopy (SEM) presents several advantages. Until now, wet bacterial specimens have been examined using atmospheric sample holders. However, images of unstained specimens in water using these holders exhibit very poor contrast and heavy radiation damage. Recently, we developed the frequency transmission electric-field (FTE) method, which facilitates the SEM observation of biological specimens in water without radiation damage. However, the signal detection system presents low sensitivity. Therefore, a high EB current is required to generate clear images, and thus reducing spatial resolution and inducing thermal damage to the samples. Here a high-sensitivity detection system is developed for the FTE method, which enhances the output signal amplitude by hundredfold. The detection signal was highly enhanced when voltage was applied to the metal layer on silicon nitride thin film. This enhancement reduced the EB current and improved the spatial resolution as well as the signal-to-noise ratio. The spatial resolution of a high-sensitive FTE system is 41 nm, which is considerably higher than previous FTE system. New FTE system can easily be utilised to examine various unstained biological specimens in water, such as living bacteria and viruses.

  14. Heme oxygenase-1 induction alters chemokine regulation and ameliorates human immunodeficiency virus-type-1 infection in lipopolysaccharide-stimulated macrophages

    SciTech Connect (OSTI)

    Zhou, Zhao-Hua; Kumari, Namita; Nekhai, Sergei; Clouse, Kathleen A.; Wahl, Larry M.; Yamada, Kenneth M.; Dhawan, Subhash

    2013-06-07

    Highlights: •Lipopolysaccharide stimulation of heme oxygenase-1 (HO-1) ameliorated HIV-1 infection of primary human macrophages. •The partial protection by HO-1 against HIV infection was associated with induction of chemokines such as MIP1? and MIP1?. •This mechanism explains lipopolysaccharide-stimulated HO-1-mediated inhibition of HIV-1 infection of macrophages. -- Abstract: We have elucidated a putative mechanism for the host resistance against HIV-1 infection of primary human monocyte-derived macrophages (MDM) stimulated with lipopolysaccharide (LPS). We show that LPS-activated MDM both inhibited HIV-1 entry into the cells and were refractory to post-entry productive viral replication. LPS-treated cells were virtually negative for mature virions as revealed by transmission electron microscopy. LPS activation of MDM markedly enhanced the expression of heme oxygenase-1 (HO-1), a potent inducible cytoprotective enzyme. Increased HO-1 expression was accompanied by elevated production of macrophage inflammatory chemokines (MIP1? and MIP1?) by LPS-activated MDM, significantly decreased surface chemokine receptor-5 (CCR-5) expression, and substantially reduced virus replication. Treatment of cells with HO-1 inhibitor SnPP IX (tin protoporphyrin IX) attenuated the LPS-mediated responses, HIV-1 replication and secretion of MIP1?, MIP1?, and LD78? chemokines with little change in surface CCR-5 expression. These results identify a novel role for HO-1 in the modulation of host immune response against HIV infection of MDM.

  15. The tale of a modern animal plague: Tracing the evolutionary history and determining the time-scale for foot and mouth disease virus

    SciTech Connect (OSTI)

    Tully, Damien C. Fares, Mario A.

    2008-12-20

    Despite significant advances made in the understanding of its epidemiology, foot and mouth disease virus (FMDV) is among the most unexpected agricultural devastating plagues. While the disease manifests itself as seven immunologically distinct strains their origin, population dynamics, migration patterns and divergence times remain unknown. Herein we have assembled a comprehensive data set of gene sequences representing the global diversity of the disease and inferred the time-scale and evolutionary history for FMDV. Serotype-specific rates of evolution and divergence times were estimated using a Bayesian coalescent framework. We report that an ancient precursor FMDV gave rise to two major diversification events spanning a relatively short interval of time. This radiation event is estimated to have taken place towards the end of the 17th and the beginning of the 18th century giving us the present circulating Euro-Asiatic and South African viral strains. Furthermore our results hint that Europe acted as a possible hub for the disease from where it successfully dispersed elsewhere via exploration and trading routes.

  16. Structural Analysis of a Viral Ovarian Tumor Domain Protease from the Crimean-Congo Hemorrhagic Fever Virus in Complex with Covalently Bonded Ubiquitin

    SciTech Connect (OSTI)

    Capodagli, Glenn C.; McKercher, Marissa A.; Baker, Erica A.; Masters, Emily M.; Brunzelle, Joseph S.; Pegan, Scott D.

    2014-10-02

    Crimean-Congo hemorrhagic fever (CCHF) virus is a tick-borne, negative-sense, single-stranded RNA [ssRNA(-)] nairovirus that produces fever, prostration, and severe hemorrhages in humans. With fatality rates for CCHF ranging up to 70% based on several factors, CCHF is considered a dangerous emerging disease. Originally identified in the former Soviet Union and the Congo, CCHF has rapidly spread across large sections of Europe, Asia, and Africa. Recent reports have identified a viral homologue of the ovarian tumor protease superfamily (vOTU) within its L protein. This protease has subsequently been implicated in downregulation of the type I interferon immune response through cleavage of posttranslational modifying proteins ubiquitin (Ub) and the Ub-like interferon-simulated gene 15 (ISG15). Additionally, homologues of vOTU have been suggested to perform similar roles in the positive-sense, single-stranded RNA [ssRNA(+)] arteriviruses. By utilizing X-ray crystallographic techniques, the structure of vOTU covalently bound to ubiquitin propylamine, a suicide substrate of the enzyme, was elucidated to 1.7 {angstrom}, revealing unique structural elements that define this new subclass of the OTU superfamily. In addition, kinetic studies were carried out with aminomethylcoumarin (AMC) conjugates of monomeric Ub, ISG15, and NEDD8 (neural precursor cell expressed, developmentally downregulated 8) substrates in order to provide quantitative insights into vOTU's preference for Ub and Ub-like substrates.

  17. Flow cytometric detection of human immunodeficiency virus type 1 proviral DNA by the polymerase chain reaction incorporating digoxigenin- or fluorescein-labeled dUTP

    SciTech Connect (OSTI)

    Yang, Gang; Olson, J.C.; Pu, R.; Vyas, G.N.

    1995-10-01

    Serological assays are routinely used in the laboratory diagnosis of human immunodeficiency virus type-1 (HrV-1) infection, but the polymerase chain reaction (PCR) is ultimately the most sensitive and direct method for establishing definitive diagnosis. As an alternative to the conventional radioactive PCR procedure we have developed and evaluated a pair of rapid nonradioisotopic flow cytometric detection methods. Using heminested PCR we directly incorporated fluorescein-12-dUTP (fluo-dUTP) or digoxigenin-11-dUTP (dig-dUTP) into the PCR-amplicons. The labeled amplicons were hybridized with biotinylated antisense and sense probes, followed by capture of the hybrid DNA using streptavidin-coated beads which were finally analyzed in a flow cytometer by (1) direct detection of the fluorescence intensity of the amplicons incorporating fluo-dUTP and (2) immunodetection of the amplicons incorporating dig-dUTP by anti-digoxigenin IgG labeled with fluorescein isothiocyanate (FITC). Although both assays were functionally comparable with radiolabeled probe in reliably detecting as low as five copies of HIV-1 proviral DNA sequences, the immunodetection of dig-dUTP consistently yielded higher mean channel fluorescence and gave a stable signal over an extended period of 12-14 weeks. In testing a panel of 20 pedigreed PBMC specimens from blood donors with or without HIV-1 infection, the results of both flow cytometric assays were identical with those of the conventional radioactive procedure. Therefore, we conclude that the dig-dUTP incorporation in amplicons, hybridization with a pair of sense-antisense biotinylated probes and immunodetection of hybrids by flow cytometric analyses is the nonisotopic method of choice for PCR-diagnosis of HIV-1 infection. 21 refs., 2 figs., 4 tabs.

  18. Structure and Mutagenesis of the Parainfluenza Virus 5 Hemagglutinin-Neuraminidase Stalk Domain Reveals a Four-Helix Bundle and the Role of the Stalk in Fusion Promotion

    SciTech Connect (OSTI)

    Bose, Sayantan; Welch, Brett D.; Kors, Christopher A.; Yuan, Ping; Jardetzky, Theodore S.; Lamb, Robert A.

    2014-10-02

    Paramyxovirus entry into cells requires the fusion protein (F) and a receptor binding protein (hemagglutinin-neuraminidase [HN], H, or G). The multifunctional HN protein of some paramyxoviruses, besides functioning as the receptor (sialic acid) binding protein (hemagglutinin activity) and the receptor-destroying protein (neuraminidase activity), enhances F activity, presumably by lowering the activation energy required for F to mediate fusion of viral and cellular membranes. Before or upon receptor binding by the HN globular head, F is believed to interact with the HN stalk. Unfortunately, until recently none of the receptor binding protein crystal structures have shown electron density for the stalk domain. Parainfluenza virus 5 (PIV5) HN exists as a noncovalent dimer-of-dimers on the surface of cells, linked by a single disulfide bond in the stalk. Here we present the crystal structure of the PIV5-HN stalk domain at a resolution of 2.65 {angstrom}, revealing a four-helix bundle (4HB) with an upper (N-terminal) straight region and a lower (C-terminal) supercoiled part. The hydrophobic core residues are a mix of an 11-mer repeat and a 3- to 4-heptad repeat. To functionally characterize the role of the HN stalk in F interactions and fusion, we designed mutants along the PIV5-HN stalk that are N-glycosylated to physically disrupt F-HN interactions. By extensive study of receptor binding, neuraminidase activity, oligomerization, and fusion-promoting functions of the mutant proteins, we found a correlation between the position of the N-glycosylation mutants on the stalk structure and their neuraminidase activities as well as their abilities to promote fusion.

  19. ARM - Field Campaign - Columbia Basin Wind Energy Study

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    govCampaignsColumbia Basin Wind Energy Study Campaign Links Outsmarting the Wind -- U.S. News Science Old meteorological techniques used in new wind farm study -- EcoSeed ARM Data Discovery Browse Data Comments? We would love to hear from you! Send us a note below or call us at 1-888-ARM-DATA. Send Campaign : Columbia Basin Wind Energy Study 2010.09.27 - 2011.05.31 Lead Scientist : Larry Berg For data sets, see below. Abstract The primary focus of this study was to obtain a multi-season data set

  20. 2010 | U.S. DOE Office of Science (SC)

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    0 News News Home Featured Articles 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 Science Headlines Science Highlights Presentations & Testimony News Archives Communications and Public Affairs Contact Information Office of Science U.S. Department of Energy 1000 Independence Ave., SW Washington, DC 20585 P: (202) 586-5430 Featured Articles 2010 Print Text Size: A A A FeedbackShare Page A line of windmills in the sunset 12.27.10From the Labs Outsmarting the Wind External link

  1. Activated Carbon Injection

    SciTech Connect (OSTI)

    2014-07-16

    History of the Clean Air Act and how the injection of carbon into a coal power plant's flu smoke can reduce the amount of mercury in the smoke.

  2. 1

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    can say this because of the model they have constructed. Using historical data, a mathematical representation of how flu spreads through a population, and data for the current...

  3. One Vaccine Leads to Another

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    particular-have led to vaccines against other diseases, like the flu and bacterial meningitis. Often, nontoxic forms of various disease toxins are used to make vaccines,...

  4. ORISE: Process and Program Evaluation

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    (measles, mumps and rubella) vaccine Immunization of health care workers against 2009 influenza A (H1N1) Vaccination of CDC employees against seasonal flu Factors influencing...

  5. Activated Carbon Injection

    ScienceCinema (OSTI)

    None

    2014-07-22

    History of the Clean Air Act and how the injection of carbon into a coal power plant's flu smoke can reduce the amount of mercury in the smoke.

  6. ALSNews Vol. 338

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    to the future of scientific research. Read more... Toward Design of a Universal Flu Vaccine Scientists have determined the structures of antibodies that protect against broad...

  7. Impact of mammalian megaherbivores on global methane examined

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    that this winter's flu season is most likely to peak in February across much of the United States. The scientists can say this because of the model they have constructed....

  8. Site Index - HPMC Occupational Health Services

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Flu Prevention Hand Washing Healthy Sleep Heat Stress Radon Signs of a Heart Attack "Cough CPR:" Urban Myth Signs of a Stroke Coping with Stress & Change Skin Cancer Awareness...

  9. SSRL HEADLINES September 2000

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    the Flu". The School seemed a great success for students and tutors alike with much being learned and information exchanged. A SMB Summer School will become an annual event at...

  10. SSRL HEADLINES November 2009

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    ... Flu Symptoms include fever, cough, sore throat, runny or stuffy nose, body aches, ... Cover your nose and mouth with a tissue when you cough or sneeze. Throw the tissue in the ...

  11. DOE - NNSA/NSO -- SiteLines - Issue 137

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    ... human flu and include fever, cough, sore throat, body aches, headache, chills and fatigue. ... What you can do to stay healthy: q Cover your nose and mouth with a tissue when you cough ...

  12. DOE - NNSA/NSO -- SiteLines - Issue 138

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    ... human flu and include fever, cough, sore throat, body aches, headache, chills and fatigue. ... yourself and others: q Cover your nose and mouth with a tissue when you cough or sneeze. ...

  13. Designing Turbulence Los Alamos Institutes

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    ... On April 1, 2009, a 10-year-old boy was admitted to an urgent care clinic in San Diego County, California, with flu-like symptoms: fever, cough, and vomiting. By chance, the clinic ...

  14. 2014 - 09 | Jefferson Lab

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    Appraisal Process Begins Today, 9292014 Mon, 09292014 - 2:02pm Occupational Medicine Offers Staff Flu Vaccines by Appointment Thu, 09252014 - 7:45am 12 GeV CEBAF...

  15. Welcome to Stanford Synchrotron Radiation Lightsource | Stanford...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    SSRL Science in SLAC Today Q&A: Biologist Describes Milestone toward a Universal Flu Vaccine SSRL Upgrades, Adds Equipment for Next Round of Experiments X-ray Microscope Reveals...

  16. Press Releases | Stanford Synchrotron Radiation Lightsource

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    Highlight) May 5, 2010 Scientists Reveal How Genetic Mutations May Cause Type 1 Diabetes (see Scripps News & Views) May 3, 2010 Why Young Are Most Affected by Swine Flu...

  17. ORISE: H1N1 Media Analysis | How ORISE is Making a Difference

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    H1N1 map This map represents the geographic origin or location of daily news articles related to H1N1 flu. The map is generated out of ORISE's Auto-INFORM database, which...

  18. Designer Proteins Target Epstein-Barr-Virus-Associated Cancer

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    "de novo" is not a new field, but until recently designer proteins were rarely also functional. In this study, new design approaches were defined and then used successfully...

  19. ALS Capabilities Reveal Multiple Functions of Ebola Virus

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    Society for the Promotion of Science, and the Japan Ministry of Education, Culture, Sports, Science, and Technology. Operation of the ALS is supported by the U.S. Department of...

  20. Immunogenic compositions comprising human immunodeficiency virus (HIV) mosaic Nef proteins

    DOE Patents [OSTI]

    Korber, Bette T. (Los Alamos, NM); Perkins, Simon (Los Alamos, NM); Bhattacharya, Tanmoy (Los Alamos, NM); Fischer, William M. (Los Alamos, NM); Theiler, James (Los Alamos, NM); Letvin, Norman (Boston, MA); Haynes, Barton F. (Durham, NC); Hahn, Beatrice H. (Birmingham, AL); Yusim, Karina (Los Alamos, NM); Kuiken, Carla (Los Alamos, NM)

    2012-02-21

    The present invention relates to mosaic clade M HIV-1 Nef polypeptides and to compositions comprising same. The polypeptides of the invention are suitable for use in inducing an immune response to HIV-1 in a human.

  1. Human immunodeficiency virus type 1 clade M mosaic gag polypeptides

    DOE Patents [OSTI]

    Korber, Bette T; Perkins, Simon; Bhattacharya, Tanmoy; Fischer, William M; Theiler, James; Letvin, Norman; Haynes, Barton F; Hahn, Beatrice H; Yusim, Karina; Kuiken, Carla

    2015-04-21

    The present invention relates to mosaic HIV-1 group M Gag sequences and to a composition comprising same.

  2. Mosaic protein and nucleic acid vaccines against hepatitis C virus

    DOE Patents [OSTI]

    Yusim, Karina; Korber, Bette T. M.; Kuiken, Carla L.; Fischer, William M.

    2013-06-11

    The invention relates to immunogenic compositions useful as HCV vaccines. Provided are HCV mosaic polypeptide and nucleic acid compositions which provide higher levels of T-cell epitope coverage while minimizing the occurrence of unnatural and rare epitopes compared to natural HCV polypeptides and consensus HCV sequences.

  3. Designer Proteins Target Epstein-Barr-Virus-Associated Cancer

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    analysis. A small number of the top proteins were expressed and purified from E. coli, and further binding tests selected two proteins that bound to BHRF1 with acceptable...

  4. ALS Capabilities Reveal Multiple Functions of Ebola Virus

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    up the question of whether there are other transformers or morpheeins that exist in biology and may even be linked to human disease. Research conducted by: Z.A. Bornholdt,...

  5. This is a paper model of the MS2 virus

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Researchers hope that MS2 therapies will help them around this problem. One cause of diabetes is an auto-immune reaction in which a person's immune system attacks the islet cells...

  6. Text and Structural Data Mining of Influenza Mentions in Web and Social Media

    SciTech Connect (OSTI)

    Corley, Courtney D.; Cook, Diane; Mikler, Armin R.; Singh, Karan P.

    2010-02-22

    Text and structural data mining of Web and social media (WSM) provides a novel disease surveillance resource and can identify online communities for targeted public health communications (PHC) to assure wide dissemination of pertinent information. WSM that mention influenza are harvested over a 24-week period, 5-October-2008 to 21-March-2009. Link analysis reveals communities for targeted PHC. Text mining is shown to identify trends in flu posts that correlate to real-world influenza-like-illness patient report data. We also bring to bear a graph-based data mining technique to detect anomalies among flu blogs connected by publisher type, links, and user-tags.

  7. Slide 1

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    95 Wa ste Sit es Re me dia ted 9 23 ,00 0 To ns of So il Re mo ved Fin al Re me dia tio n of 61 8-1 0 & 618 -11 Bu ria l Gr ou nd s Co mp let e 40 0 A re a Fa st Flu...

  8. Analysis of phases in the structure determination of an icosahedral virus

    SciTech Connect (OSTI)

    Plevka, Pavel; Kaufmann, BĂ€rbel; Rossmann, Michael G.

    2012-03-15

    The constraints imposed on structure-factor phases by noncrystallographic symmetry (NCS) allow phase improvement, phase extension to higher resolution and hence ab initio phase determination. The more numerous the NCS redundancy and the greater the volume used for solvent flattening, the greater the power for phase determination. In a case analyzed here the icosahedral NCS phasing appeared to have broken down, although later successful phase extension was possible when the envelope around the NCS region was tightened. The phases from the failed phase-determination attempt fell into four classes, all of which satisfied the NCS constraints. These four classes corresponded to the correct solution, opposite enantiomorph, Babinet inversion and opposite enantiomorph with Babinet inversion. These incorrect solutions can be seeded from structure factors belonging to reciprocal-space volumes that lie close to icosahedral NCS axes where the structure amplitudes tend to be large and the phases tend to be 0 or {pi}. Furthermore, the false solutions can spread more easily if there are large errors in defining the envelope designating the region in which NCS averaging is performed.

  9. Mosaic clade M human immunodeficiency virus type 1 (HIV-1) envelope immunogens

    DOE Patents [OSTI]

    Korber, Bette T. (Los Alamos, NM); Fischer, William (Los Alamos, NM); Liao, Hua-Xin (Durham, NC); Haynes, Barton F. (Durham, NC); Letvin, Norman (Boston, MA); Hahn; Beatrice H. (Birmingham, AL)

    2011-05-31

    The present invention relates to mosaic clade M HIV-1 Env polypeptides and to compositions comprising same. The polypeptides of the invention are suitable for use in inducing an immune response to HIV-1 in a human.

  10. Nucleic acids encoding mosaic clade M human immunodeficiency virus type 1 (HIV-1) envelope immunogens

    DOE Patents [OSTI]

    Korber, Bette T; Fischer, William; Liao, Hua-Xin; Haynes, Barton F; Letvin, Norman; Hahn, Beatrice H

    2015-04-21

    The present invention relates to nucleic acids encoding mosaic clade M HIV-1 Env polypeptides and to compositions and vectors comprising same. The nucleic acids of the invention are suitable for use in inducing an immune response to HIV-1 in a human.

  11. Nucleic acids encoding modified human immunodeficiency virus type 1 (HIV-1) group M consensus envelope glycoproteins

    DOE Patents [OSTI]

    Haynes, Barton F. (Durham, NC); Gao, Feng (Durham, NC); Korber, Bette T. (Los Alamos, NM); Hahn, Beatrice H. (Birmingham, AL); Shaw, George M. (Birmingham, AL); Kothe, Denise (Birmingham, AL); Li, Ying Ying (Hoover, AL); Decker, Julie (Alabaster, AL); Liao, Hua-Xin (Chapel Hill, NC)

    2011-12-06

    The present invention relates, in general, to an immunogen and, in particular, to an immunogen for inducing antibodies that neutralizes a wide spectrum of HIV primary isolates and/or to an immunogen that induces a T cell immune response. The invention also relates to a method of inducing anti-HIV antibodies, and/or to a method of inducing a T cell immune response, using such an immunogen. The invention further relates to nucleic acid sequences encoding the present immunogens.

  12. Viruses in laboratory-reared cactus moth, Cactoblastis cactorum (Lepidoptera: Pyralidae)

    SciTech Connect (OSTI)

    Marti, O.G.; Myers, R.E.; Carpenter, J.E.; Styer, E.L.

    2007-03-15

    The cactus moth, Cactoblastis cactorum (Lepidoptera: Pyralidae: Phycitinae), is a non-native species threatening a variety of native cacti, particularly endangered species of Opuntia (Zimmerman et al. 2001), on the coast of the Gulf of Mexico. Cactoblastis cactorum populations have expanded from Florida northward along the Atlantic coast as far as Charleston, SC, and westward along the Gulf of Mexico to Dauphin Island, south of Mobile, AL. It is feared that further movement to the west will allow C. cactorum to enter the US desert Southwest and Mexico, particularly the latter. Numerous cactus species, especially those of the genera Opuntia and Nopalea, are native to the U.S. and Mexico. Local economies based on agricultural and horticultural uses of cacti could be devastated by C. cactorum (Vigueras and Portillo 2001). A bi-national control program between the US and Mexico is being developed, utilizing the sterile insect technique (SIT). In the SIT program, newly emerged moths are irradiated with a {sup 60}Co source and released to mate with wild individuals. The radiation dose completely sterilizes the females and partially sterilizes the males. When irradiated males mate with wild females, the F1 progeny of these matings are sterile. In order for the SIT program to succeed, large numbers of moths must be reared from egg to adult on artificial diet in a quarantined rearing facility (Carpenter et al. 2001). Irradiated insects must then be released in large numbers at the leading edge of the invasive population and at times which coincide with the presence of wild individuals available for mating. Mortality from disease in the rearing colony disrupts the SIT program by reducing the numbers of insects available for release.

  13. Discovery of Disease Co-occurrence Patterns from Electronic Healthcare Reimbursement Claims Data

    SciTech Connect (OSTI)

    Ramanathan, Arvind; Pullum, Laura L; Hobson, Tanner C; Quinn, Shannon; Chennubhotla, Chakra; Valkova, Silvia

    2014-01-01

    Effective public health surveillance is important for national secu- rity. With novel emerging infectious diseases being reported across different parts of the world, there is a need to build effective bio- surveillance systems that can track, monitor and report such events in a timely manner. Additionally, there is a need to identify sus- ceptible geographic regions/populations where these diseases may have a significant impact and design preemptive strategies to tackle them. With the digitization of health related information through electronic health records (EHR) and electronic healthcare claim re- imbursements (eHCR), there is a tremendous opportunity to ex- ploit these datasets for public health surveillance. In this paper, we present our analysis on the use of eHCR data for bio-surveillance by studying the 2009-2010 H1N1 pandemic flu season. We present a novel approach to extract spatial and temporal patterns of flu in- cidence across the United States (US) from eHCRs and find that a small, but distinct set of break-out patterns govern the flu and asthma incidence rates across the entire country. Further, we ob- serve a distinct temporal lag in the onset of flu when compared to asthma across geographic regions in the US. The patterns extracted from the data collectively indicate how these break-out patterns are coupled, even though the flu represents an infectious disease whereas asthma represents a typical chronic condition. Taken to- gether, our approach demonstrates how mining eHCRs can provide novel insights in tackling public health concerns.

  14. Search for: All records | SciTech Connect

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    Selective deposition of nanostructured ruthenium oxide using Tobacco mosaic virus for ... Solid flexible electrochemical supercapacitor using Tobacco mosaic virus nanostructures ...

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    ... Selective deposition of nanostructured ruthenium oxide using Tobacco mosaic virus for ... Solid flexible electrochemical supercapacitor using Tobacco mosaic virus nanostructures ...

  16. News Item

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    4, 2014 Time: 11:00 am Speaker: Dr. David Baker, University of Washington Title: Design of Protein Structures, Functions and Assemblies Location: 67-3111 Chemla Room Hosted by Ron Zuckermann Abstract: I will describe recent advances in computational protein design which allow the generation of new protein structures and functions. I will describe the use of these methods to design ultra-stable idealized proteins, flu neutralizing proteins, high affinity ligand binding proteins, and self

  17. new Global Bio Lab

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    pandemic detection tool ready to fight flu June 9, 2009 Los Alamos and Agilent Technologies develop first high-throughput system to be deployed at UCLA's new Global Bio Lab LOS ALAMOS, New Mexico, June 9, 2009-In a joint effort by national laboratory-, university- and private-sector institutions, researchers are developing new tools for rapidly characterizing biological pathogens that could give rise to potentially deadly pandemics such as Influenza A (H1N1).The first tool, an automated

  18. 2016 | U.S. DOE Office of Science (SC)

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    6 News News Home Featured Articles Science Headlines 2015 2014 2013 2016 Beam-Beam Compensation Scheme Doubles Proton-Proton Collision Rates at RHIC External link PPPL Physicists Simulate Innovative Method for Starting Up Tokamaks Without Using a Solenoid External link ORNL on Team Officially Recognized for Elements 115, 117 Discovery External link Q&A: Biologist Describes Milestone Toward a Universal Flu Vaccine External link Finding New Ways to Optimize Old Codes External link A Nanoscale

  19. Los Alamos National Lab: National Security Science

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Science in 60 Flu Video of the Week Forecasting epidemics like weather Real-time data from Wikipedia and social media helps to model disease spread watch cube sat awardees Los Alamos in the News Kudos to "cube" satellite scientists Agile space systems delivered for DOE, military more mosquito Los Alamos in the News Why is Zika now a threat? Population growth, rising temperatures, embryonic immune systems says Lab scientist more Van Allen Belts video screenshot Picture of the Week

  20. The effects of 5-fluorouracil and doxorubicin on expression of human immunodeficiency virus type 1 long terminal repeat

    SciTech Connect (OSTI)

    Panozzo, J.; Akan, E.; Griffiths, T.D.; Woloschak, G.E.

    1996-03-01

    Previous work by many groups has documented induction of the HIV-LTR following exposure of cells to ultraviolet light and other DNA damaging agents. Our experiments set out to determine the relative activation or repression of the HIV-LTR in response to two classes of chemotherapeutic agents: Doxorubicin is a DNA-damage inducing agent, and 5-fluorouracil has an antimetabolic mode of action. Using HeLa cells stably transfected with a construct in which HIV-LTR drives expression of the chloramphenicol acetyl transferase reporter gene, we demonstrated an up to 10-fold induction following doxorubicin treatment in 24 h post-treatment. This induction was repressed by treatment with salicylic acid, suggesting a role for prostaglandin/cyclo-oxygenase pathways and/or NFKB in the inductive response. Induction by 5-fluorouracil, in contrast, was more modest (two-fold at most) though it was consistently elevated over controls.

  1. Search for: All records | SciTech Connect

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    ... that inhibits the replication of many viruses such as Moloney murine leukemia virus (MLV) and Sindbis virus (SIN) by preventing the accumulation of viral mRNA in the cytoplasm. ...

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    ... and development of computational tools to predict virus-host protein interactions. ... goal 1. We generated and characterized suitable primers for West Nile Virus RNA detection. ...

  3. Selective deposition of nanostructured ruthenium oxide using...

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    ruthenium oxide using Tobacco mosaic virus for micro-supercapacitors in solid Nafion ... Title: Selective deposition of nanostructured ruthenium oxide using Tobacco mosaic virus ...

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    renormalization (3) trajectories (3) aids virus (2) lattice field theory (2) perturbation ... Full Text Available December 2014 Human immunodeficiency virus type 1 clade M mosaic gag ...

  5. Recombination enhances HIV-1 envelope diversity by facilitating...

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    plasma virus population Prev Next Title: Recombination enhances HIV-1 envelope diversity by facilitating the survival of latent genomic fragments in the plasma virus ...

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    renormalization (3) trajectories (3) aids virus (2) lattice field theory (2) perturbation ... Immunogenic compositions comprising human immunodeficiency virus (HIV) mosaic Nef proteins ...

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    ... are host cell targets for the matrix (M) protein of vesicular stomatitis virus (VSV). ... by the vesicular stomatitis virus matrix protein to inhibit host cell nuclear export. ...

  8. Structure of the cleavage-activated prefusion form of the parainfluenz...

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    the parainfluenza virus 5 fusion protein Citation Details In-Document Search Title: Structure of the cleavage-activated prefusion form of the parainfluenza virus 5 fusion protein ...

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    ... Structure of the Newcastle disease virus hemagglutinin-neuraminidase (HN) ectodomain ... Mutations of the Newcastle disease virus HN stalk region have been shown to affect both F ...

  10. Solid flexible electrochemical supercapacitor using Tobacco mosaic...

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    mosaic virus nanostructures and ALD ruthenium oxide Citation Details In-Document Search Title: Solid flexible electrochemical supercapacitor using Tobacco mosaic virus ...

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    for the patterning and templated synthesis of virus-structured nanomaterials in two- and three-dimensional microfabricated architectures using the Tobacco mosaic virus (TMV). ...

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    ... from the Crimean-Congo Hemorrhagic Fever Virus in Complex with Covalently Bonded ... Crimean-Congo hemorrhagic fever (CCHF) virus is a tick-borne, negative-sense, ...

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    ... (3) carcinomas (2) chemotherapy (2) aids virus (1) applied life sciences (1) beam ... immunodeficiency virus-positive (HIV+) and 3 post-solid organ transplant ID patients. ...

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    ... replication competent virus is detected even when other forms may have been transmitted. ... of latent genomic fragments in the plasma virus population Immonen, Taina T. ; Conway, ...

  15. Strategic Priming with Multiple Antigens can Yield Memory Cell...

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    ... Protective vaccines against smallpox (Vaccinia virus) produce T cell populations that are ... CD8+ T cell immunodominance in primary and secondary influenza virus infections. J. Exp. ...

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    of latent genomic fragments in the plasma virus population Immonen, Taina T. ; Conway, ... Virus released from activated latent cells competes against variants that have continually ...

  17. Recombination elevates the effective evolutionary rate and facilitates...

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    replication competent virus is detected even when other forms may have been transmitted. ... Subject: 59 BASIC BIOLOGICAL SCIENCES HV-1; MTCT; transmittedfounder virus; ...

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    ... of latent genomic fragments in the plasma virus population Immonen, Taina T. ; Conway, ... Virus released from activated latent cells competes against variants that have continually ...

  19. "Title","Creator/Author","Publication Date","OSTI Identifier...

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    ... Virus andor bacteria are pathogens that can be transported by the disclosed method. ... Virus andor bacteria are pathogens that can be transported by the disclosed method. ...

  20. Rational design and adaptive management of combination therapies...

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    therapies for Hepatitis C virus infection Prev Next Title: Rational design and adaptive management of combination therapies for Hepatitis C virus infection Recent ...

  1. Rational Design and Adaptive Management of Combination Therapies...

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    of Combination Therapies for Hepatitis C Virus Infection CrossMark click for updates n ... Design and Adaptive Management of Combination Therapies for Hepatitis C Virus Infection. ...

  2. Analysis of the Argonne distance tabletop exercise method.

    SciTech Connect (OSTI)

    Tanzman, E. A.; Nieves, L. A.; Decision and Information Sciences

    2008-02-14

    The purpose of this report is to summarize and evaluate the Argonne Distance Tabletop Exercise (DISTEX) method. DISTEX is intended to facilitate multi-organization, multi-objective tabletop emergency response exercises that permit players to participate from their own facility's incident command center. This report is based on experience during its first use during the FluNami 2007 exercise, which took place from September 19-October 17, 2007. FluNami 2007 exercised the response of local public health officials and hospitals to a hypothetical pandemic flu outbreak. The underlying purpose of the DISTEX method is to make tabletop exercising more effective and more convenient for playing organizations. It combines elements of traditional tabletop exercising, such as scenario discussions and scenario injects, with distance learning technologies. This distance-learning approach also allows playing organizations to include a broader range of staff in the exercise. An average of 81.25 persons participated in each weekly webcast session from all playing organizations combined. The DISTEX method required development of several components. The exercise objectives were based on the U.S. Department of Homeland Security's Target Capabilities List. The ten playing organizations included four public health departments and six hospitals in the Chicago area. An extent-of-play agreement identified the objectives applicable to each organization. A scenario was developed to drive the exercise over its five-week life. Weekly problem-solving task sets were designed to address objectives that could not be addressed fully during webcast sessions, as well as to involve additional playing organization staff. Injects were developed to drive play between webcast sessions, and, in some cases, featured mock media stories based in part on player actions as identified from the problem-solving tasks. The weekly 90-minute webcast sessions were discussions among the playing organizations that were moderated by a highly-qualified public health physician, who reviewed key scenario developments and player actions, as well as solicited input from each playing organization. The exercise control structure included trusted agents who oversaw exercise planning, playing organization points of contact to ensure exercise coordination, and exercise controller/evaluators to initiate and oversee exercise play. A password-protected exercise website was designed for FluNami 2007 to serve as a compartmentalized central information source, and for transmitting exercise documents. During the course of FluNami 2007, feedback on its quality was collected from players and controller/evaluators. Player feedback was requested at the conclusion of each webcast, upon completion of each problem-solving task, and on October 17, 2007, after the final webcast session had ended. The overall average score given to FluNami 2008 by the responding players was 3.9 on a five-point scale. In addition, suggestions for improving the process were provided by Argonne controller/evaluators after the exercise concluded. A series of recommendations was developed based on feedback from the players and controller/evaluators. These included improvements to the exercise scope and objectives, the problem-solving tasks, the scenarios, exercise control, the webcast sessions, the exercise website, and the player feedback process.

  3. Hybrid fluidized bed combuster

    DOE Patents [OSTI]

    Kantesaria, Prabhudas P. (Windsor, CT); Matthews, Francis T. (Poquonock, CT)

    1982-01-01

    A first atmospheric bubbling fluidized bed furnace is combined with a second turbulent, circulating fluidized bed furnace to produce heat efficiently from crushed solid fuel. The bed of the second furnace receives the smaller sizes of crushed solid fuel, unreacted limestone from the first bed, and elutriated solids extracted from the flu gases of the first bed. The two-stage combustion of crushed solid fuel provides a system with an efficiency greater than available with use of a single furnace of a fluidized bed.

  4. BSM Newsletter February 2016

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    February 2016 At the Bradbury Latest Issue:March 2016 all issues All Issues » submit IN THIS ISSUE What do you think of our new look and feel? A short survey on our new look February most likely month for flu season to peak From our pages Inspecting a microscope A new artifact joins our collection Tobacco and radiation? Our science question of the month Top 10 science stories of the year From our pages Conifer disapperance due to climate change? From our pages EVENTS What's the matter with

  5. Science on Tap - Forecasting illness

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Science on Tap - Forecasting illness Science on Tap - Forecasting illness WHEN: Mar 17, 2016 5:30 PM - 7:00 PM WHERE: UnQuarked Wine Room 145 Central Park Square, Los Alamos, New Mexico 87544 USA CONTACT: Linda Anderman (505) 665-9196 CATEGORY: Bradbury INTERNAL: Calendar Login Event Description Mark your calendars for this event held every third Thursday from 5:30 to 7 p.m. A short presentation is followed by a lively discussion on a different subject each month. Forecasting the flu (and other

  6. 2009 - 09 | Jefferson Lab

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    September 2009 Mon, 09/28/2009 - 3:00pm Lab Staff, Users, Students, Guests Celebrate 25 Years of Science Tuesday, Sept. 29 Wed, 09/23/2009 - 3:00pm Secretary Chu Visits JLab for Anniversary Event Mon, 09/21/2009 - 3:00pm Important Parking, Traffic Guidance Before, During 25th Anniversary Event Thu, 09/17/2009 - 3:00pm JLab Guidance Regarding Flu Prevention Tue, 09/15/2009 - 3:00pm Lab Computing: critical patches to be delivered tonight Thu, 09/10/2009 - 3:00pm Large-format printer in Document

  7. 2011 - 09 | Jefferson Lab

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    September 2011 Tue, 09/27/2011 - 3:00pm Performance Appraisal Process Begins 9/27/2011 Mon, 09/26/2011 - 3:00pm Occ. Med. Offers Staff Flu Vaccines by Appointment Thu, 09/15/2011 - 3:00pm JLab Adopts Event Policy to Avoid Scheduling Conflicts Tue, 09/13/2011 - 3:00pm CS Parking Lot Closed During Test Lab Exterior Painting Thu, 09/01/2011 - 3:00pm United Way Annual Appeal Underway at JLab Thu, 09/01/2011 - 3:00pm Invitation to Celebrate JLab Founding Director's Contributions

  8. Microsoft Word - Oct-2015 Newsletter_tah.docx

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Special Lecture: Jews in Theory featuring Jack Shlachter 3:00 PM to 4:00 PM Scientist in the Spotlight Is the Flu in Your Future? 10:00 AM to 12:00 PM Ada Lovelace Day Events Science on Tap 5:30 PM to 7:00 PM @ UnQuarked Wine Room 145 Central Park Square Los Alamos, New Mexico Women in STEM Panel 7:00 PM to 8:30 PM @ Mesa Public Library 2400 Central Avenue Los Alamos, New Mexico Nuclear Science Week Visit the museum and learn about nuclear science High-Tech Halloween 4:00 PM to 6:30 PM

  9. May

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    May /newsroom/_assets/images/newsroom-icon.jpg May We are your source for reliable, up-to-date news and information; our scientists and engineers can provide technical insights on our innovations for a secure nation. Los Alamos National Laboratory sits on top of a once-remote mesa in northern New Mexico with the Jemez mountains as a backdrop to research and innovation covering multi-disciplines from bioscience, sustainable energy sources, to plasma physics and new materials. Battling bird flu by

  10. A role for granulocyte-macrophage colony-stimulating factor in the regulation of CD8{sup +} T cell responses to rabies virus

    SciTech Connect (OSTI)

    Wanjalla, Celestine N.; Goldstein, Elizabeth F.; Wirblich, Christoph; Schnell, Matthias J.

    2012-05-10

    Inflammatory cytokines have a significant role in altering the innate and adaptive arms of immune responses. Here, we analyzed the effect of GM-CSF on a RABV-vaccine vector co-expressing HIV-1 Gag. To this end, we immunized mice with RABV expressing HIV-1 Gag and GM-CSF and analyzed the primary and recall CD8{sup +} T cell responses. We observed a statistically significant increase in antigen presenting cells (APCs) in the spleen and draining lymph nodes in response to GM-CSF. Despite the increase in APCs, the primary and memory anti HIV-1 CD8{sup +} T cell response was significantly lower. This was partly likely due to lower levels of proliferation in the spleen. Animals treated with GM-CSF neutralizing antibodies restored the CD8{sup +} T cell response. These data define a role of GM-CSF expression, in the regulation of the CD8{sup +} T cell immune responses against RABV and has implications in the use of GM-CSF as a molecular adjuvant in vaccine development.

  11. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... is described for unliganded Vaccinia virus poly(A) polymerase monomer (VP55), showing ... Vaccinia virus poly(A) polymerase (VP55) is the only known polymerase that can translocate ...

  12. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... AAnn Arbor660 (AA ca) (H2N2) virus in mice and ferrets to evaluate its use in the event of an H2 influenza pandemic. The AA ca virus was restricted in replication in the ...

  13. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    Assembly of the Ebola Virus Nucleoprotein from a Chaperoned VP35 Complex Kirchdoerfer, ... Structure of Hepatitis C virus envelope glycoprotein E1 antigenic site 314-324 in complex ...

  14. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ...erazine-2-carboxamides to the hepatitis C virus polymerase Gentles, Robert G. ; Sheriff, ... These compounds bind to the hepatitis C virus non-structural protein 5B (NS5B), and ...

  15. Structural basis for the antibody neutralization of Herpes simplex...

    Office of Scientific and Technical Information (OSTI)

    of Herpes simplex virus Citation Details In-Document Search Title: Structural basis for the antibody neutralization of Herpes simplex virus The gD-E317-Fab complex ...

  16. Patents -- Ivar Giaever (1976)

    Office of Scientific and Technical Information (OSTI)

    and separating select viruses, bacteria and other cells from multi-cell, bacteria or virus populations. US 3,975,238 METHOD AND APPARATUS FOR DETECTING MOLECULES IN SOLUTIONS --...

  17. SN-03 Rate Hearing (7i) Files (ratecases/sn03)

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    for any problems that may occur. Although these documents have been scanned by BPA anti-virus software, BPA cannot guarantee the files are virus-free. Notes: Some directories may...

  18. ORNL-5904 DE82 C19734 ORNL-5904 Cootr»* No. W 7405-eng-2o

    Office of Scientific and Technical Information (OSTI)

    ... R.; Mitra, S. "Restriction Map of the Single-Stranded DNA Genome of Kilham Rat Virus ... of the Restriction of the Endogenous Virus of the RFMUn Mouse," p 255. Abstracts of ...

  19. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... F Fsub 1-ATPase as biosensor to detect single virus Liu, XiaoLong ; The Key Laboratory ... as a biosensor (immuno-rotary biosensor) for the purpose of capturing single virus. ...

  20. Time-Resolved Small-Angle X-ray Scattering Studies Revealed Three Kinetic

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Stages of a T=4 Virus Maturation June 2010 Time-Resolved Small-Angle X-ray Scattering Studies Revealed Three Kinetic Stages of a T=4 Virus Maturation Most eukaryotic viruses, including HIV, influenza and herpes viruses, undergo maturation when transitioning from the noninfectious provirion to the infectious virion. Maturation processes involve reorganization of viral quaternary structure to defend viral gene from the cellular defense mechanism and lead to effective transfection. Nudaurelia

  1. Rational design and adaptive management of combination therapies for

    Office of Scientific and Technical Information (OSTI)

    Hepatitis C virus infection (Journal Article) | DOE PAGES DOE PAGES Search Results Accepted Manuscript: Rational design and adaptive management of combination therapies for Hepatitis C virus infection « Prev Next » Title: Rational design and adaptive management of combination therapies for Hepatitis C virus infection Recent discoveries of direct acting antivirals against Hepatitis C virus (HCV) have raised hopes of effective treatment via combination therapies. Yet rapid evolution and high

  2. Dr. Andrew Russo

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Disabling a Killer Virus The CAMD Protein Crystallography beamline was used to determine the structure of a protein that the Venezuelan Equine Encephalitis (VEE) virus requires for replication. VEE is a mosquito-borne virus found in Central and South America, and southern Texas. Periodic outbreaks infect tens of thousands of people and kill hundreds of thousands of horses, donkeys and mules. The virus was developed into a biological weapon during the Cold War by both the United States and the

  3. INL Cyber Security Research (2008)

    Broader source: Energy.gov [DOE]

    Cybersecurity research at INL will help protect critical infrastructure control system computers against worms and other viruses.

  4. Design Construction and Operation of a Supercritical Carbon Dioxide (sCO2) Loop for Investigation of Dry Cooling and Natural Circulation Potential for Use in Advanced Small Modular Reactors Utilizing sCO2 Power Conversion Cycles.

    SciTech Connect (OSTI)

    Middleton, Bobby D.; Rodriguez, Salvador B.; Carlson, Matthew David

    2015-11-01

    This report outlines the work completed for a Laboratory Directed Research and Development project at Sandia National Laboratories from October 2012 through September 2015. An experimental supercritical carbon dioxide (sCO 2 ) loop was designed, built, and o perated. The experimental work demonstrated that sCO 2 can be uti lized as the working fluid in an air - cooled, natural circulation configuration to transfer heat from a source to the ultimate heat sink, which is the surrounding ambient environment in most ca ses. The loop was also operated in an induction - heated, water - cooled configuration that allows for measurements of physical parameters that are difficult to isolate in the air - cooled configuration. Analysis included the development of two computational flu id dynamics models. Future work is anticipated to answer questions that were not covered in this project.

  5. Forecasting the 2013–2014 influenza season using Wikipedia

    SciTech Connect (OSTI)

    Hickmann, Kyle S.; Fairchild, Geoffrey; Priedhorsky, Reid; Generous, Nicholas; Hyman, James M.; Deshpande, Alina; Del Valle, Sara Y.; Salathé, Marcel

    2015-05-14

    Infectious diseases are one of the leading causes of morbidity and mortality around the world; thus, forecasting their impact is crucial for planning an effective response strategy. According to the Centers for Disease Control and Prevention (CDC), seasonal influenza affects 5% to 20% of the U.S. population and causes major economic impacts resulting from hospitalization and absenteeism. Understanding influenza dynamics and forecasting its impact is fundamental for developing prevention and mitigation strategies. We combine modern data assimilation methods with Wikipedia access logs and CDC influenza-like illness (ILI) reports to create a weekly forecast for seasonal influenza. The methods are applied to the 2013-2014 influenza season but are sufficiently general to forecast any disease outbreak, given incidence or case count data. We adjust the initialization and parametrization of a disease model and show that this allows us to determine systematic model bias. In addition, we provide a way to determine where the model diverges from observation and evaluate forecast accuracy. Wikipedia article access logs are shown to be highly correlated with historical ILI records and allow for accurate prediction of ILI data several weeks before it becomes available. The results show that prior to the peak of the flu season, our forecasting method produced 50% and 95% credible intervals for the 2013-2014 ILI observations that contained the actual observations for most weeks in the forecast. However, since our model does not account for re-infection or multiple strains of influenza, the tail of the epidemic is not predicted well after the peak of flu season has passed.

  6. Forecasting the 2013–2014 influenza season using Wikipedia

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Hickmann, Kyle S.; Fairchild, Geoffrey; Priedhorsky, Reid; Generous, Nicholas; Hyman, James M.; Deshpande, Alina; Del Valle, Sara Y.; Salathé, Marcel

    2015-05-14

    Infectious diseases are one of the leading causes of morbidity and mortality around the world; thus, forecasting their impact is crucial for planning an effective response strategy. According to the Centers for Disease Control and Prevention (CDC), seasonal influenza affects 5% to 20% of the U.S. population and causes major economic impacts resulting from hospitalization and absenteeism. Understanding influenza dynamics and forecasting its impact is fundamental for developing prevention and mitigation strategies. We combine modern data assimilation methods with Wikipedia access logs and CDC influenza-like illness (ILI) reports to create a weekly forecast for seasonal influenza. The methods are appliedmore » to the 2013-2014 influenza season but are sufficiently general to forecast any disease outbreak, given incidence or case count data. We adjust the initialization and parametrization of a disease model and show that this allows us to determine systematic model bias. In addition, we provide a way to determine where the model diverges from observation and evaluate forecast accuracy. Wikipedia article access logs are shown to be highly correlated with historical ILI records and allow for accurate prediction of ILI data several weeks before it becomes available. The results show that prior to the peak of the flu season, our forecasting method produced 50% and 95% credible intervals for the 2013-2014 ILI observations that contained the actual observations for most weeks in the forecast. However, since our model does not account for re-infection or multiple strains of influenza, the tail of the epidemic is not predicted well after the peak of flu season has passed.« less

  7. Activation of the PI3K-Akt pathway by human T cell leukemia virus type 1 (HTLV-1) oncoprotein Tax increases Bcl3 expression, which is associated with enhanced growth of HTLV-1-infected T cells

    SciTech Connect (OSTI)

    Saito, Kousuke; Saito, Mineki; Taniura, Naoko; Okuwa, Takako; Ohara, Yoshiro

    2010-08-01

    Bcl3 is a member of the I{kappa}B family that regulates genes involved in cell proliferation and apoptosis. Recent reports indicated that Bcl3 is overexpressed in HTLV-1-infected T cells via Tax-mediated transactivation, and acts as a negative regulator of viral transcription. However, the role of Bcl3 in cellular signal transduction and the growth of HTLV-1-infected T cells have not been reported. In this study, we showed that the knockdown of Bcl3 by short hairpin RNA inhibited the growth of HTLV-1-infected T cells. Although phosphatidylinositol-3 kinase (PI3K) inhibitor reduced Bcl3 expression, inactivation of glycogen synthase kinase 3 (GSK3), an effector kinase of the PI3K/Akt signaling pathway, restored Bcl3 expression in Tax-negative but not in Tax-positive T cells. Our results indicate that the overexpression of Bcl3 in HTLV-1-infected T cells is regulated not only by transcriptional but also by post-transcriptional mechanisms, and is involved in overgrowth of HTLV-1-infected T cells.

  8. Architecture for removable media USB-ARM

    DOE Patents [OSTI]

    Shue, Craig A.; Lamb, Logan M.; Paul, Nathanael R.

    2015-07-14

    A storage device is coupled to a computing system comprising an operating system and application software. Access to the storage device is blocked by a kernel filter driver, except exclusive access is granted to a first anti-virus engine. The first anti-virus engine is directed to scan the storage device for malicious software and report results. Exclusive access may be granted to one or more other anti-virus engines and they may be directed to scan the storage device and report results. Approval of all or a portion of the information on the storage device is based on the results from the first anti-virus engine and the other anti-virus engines. The storage device is presented to the operating system and access is granted to the approved information. The operating system may be a Microsoft Windows operating system. The kernel filter driver and usage of anti-virus engines may be configurable by a user.

  9. A bio-synthetic interface for discovery of viral entry mechanisms.

    SciTech Connect (OSTI)

    Gutzler, Mike; Maar, Dianna; Negrete, Oscar; Hayden, Carl C.; Sasaki, Darryl Yoshio; Stachowiak, Jeanne C.; Wang, Julia

    2010-09-01

    Understanding and defending against pathogenic viruses is an important public health and biodefense challenge. The focus of our LDRD project has been to uncover the mechanisms enveloped viruses use to identify and invade host cells. We have constructed interfaces between viral particles and synthetic lipid bilayers. This approach provides a minimal setting for investigating the initial events of host-virus interaction - (i) recognition of, and (ii) entry into the host via membrane fusion. This understanding could enable rational design of therapeutics that block viral entry as well as future construction of synthetic, non-proliferating sensors that detect live virus in the environment. We have observed fusion between synthetic lipid vesicles and Vesicular Stomatitis virus particles, and we have observed interactions between Nipah virus-like particles and supported lipid bilayers and giant unilamellar vesicles.

  10. Stanford Synchrotron Radiation Lightsource

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    The Lassa Virus Nucleoprotein Appears to Exhibit Conformational Control of Genome Binding January 2013 SSRL Science Summary by Lori Ann White, SLAC Office of Communications Figure Surface representation of the Lassa virus nucleoprotein showing the RNA bound in between the two sub-domains, highlighting, in particular, a deep pocket that could be a prime target for anti-virals. (Courtesy of the Ollmann Saphire lab, The Scripps Research Institute.) Lassa virus is endemic in Western Africa, and is

  11. Be aware of Zika on business, spring break travel | The Ames Laboratory

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Be aware of Zika on business, spring break travel People traveling to tropical climates on business or for spring break vacations should take precautions to avoid contracting the zika virus, according the Centers for Disease Control. The zika virus is one of several mosquito-borne that have been on the upswing in Central and South America and the Carribean. To learn more about the zika virus, check out this information

  12. 1

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    deciphers HIV attack plan March 29, 2013 Scientists get inside look at how AIDS virus grooms its assault team LOS ALAMOS, N. M., March 29, 2013-A new study by Los Alamos National Laboratory and University of Pennsylvania scientists defines previously unknown properties of transmitted HIV-1, the virus that causes AIDS. The viruses that successfully pass from a chronically infected person to a new individual are both remarkably resistant to a powerful initial human immune-response mechanism, and

  13. ALSNews Vol. 354

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    4 Print ALS Capabilities Reveal Multiple Functions of Ebola Virus ebola Researchers at the ALS have demonstrated that a protein of Ebola virus, termedVP40, undergoes dramatic refolding rearrangements to achieve three entirely different structures for three entirely separate functions in the virus life cycle. Read more... Contact: Erica Saphire An Inside Look at a MOF in Action mof Researchers have recorded the first in situ electronic-structure observations of the adsorption of carbon dioxide

  14. ALSNews Vol. 354

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    4 ALSNews Vol. 354 Print Tuesday, 24 June 2014 08:51 ALS Capabilities Reveal Multiple Functions of Ebola Virus ebola Researchers at the ALS have demonstrated that a protein of Ebola virus, termedVP40, undergoes dramatic refolding rearrangements to achieve three entirely different structures for three entirely separate functions in the virus life cycle. Read more... Contact: Erica Saphire An Inside Look at a MOF in Action mof Researchers have recorded the first in situ electronic-structure

  15. ALSNews Vol. 354

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    4 Print ALS Capabilities Reveal Multiple Functions of Ebola Virus ebola Researchers at the ALS have demonstrated that a protein of Ebola virus, termedVP40, undergoes dramatic refolding rearrangements to achieve three entirely different structures for three entirely separate functions in the virus life cycle. Read more... Contact: Erica Saphire An Inside Look at a MOF in Action mof Researchers have recorded the first in situ electronic-structure observations of the adsorption of carbon dioxide

  16. ALSNews Vol. 354

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    4 Print ALS Capabilities Reveal Multiple Functions of Ebola Virus ebola Researchers at the ALS have demonstrated that a protein of Ebola virus, termedVP40, undergoes dramatic refolding rearrangements to achieve three entirely different structures for three entirely separate functions in the virus life cycle. Read more... Contact: Erica Saphire An Inside Look at a MOF in Action mof Researchers have recorded the first in situ electronic-structure observations of the adsorption of carbon dioxide

  17. ALSNews Vol. 354

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    4 Print ALS Capabilities Reveal Multiple Functions of Ebola Virus ebola Researchers at the ALS have demonstrated that a protein of Ebola virus, termedVP40, undergoes dramatic refolding rearrangements to achieve three entirely different structures for three entirely separate functions in the virus life cycle. Read more... Contact: Erica Saphire An Inside Look at a MOF in Action mof Researchers have recorded the first in situ electronic-structure observations of the adsorption of carbon dioxide

  18. ALSNews Vol. 354

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    ALSNews Vol. 354 Print ALS Capabilities Reveal Multiple Functions of Ebola Virus ebola Researchers at the ALS have demonstrated that a protein of Ebola virus, termedVP40, undergoes dramatic refolding rearrangements to achieve three entirely different structures for three entirely separate functions in the virus life cycle. Read more... Contact: Erica Saphire An Inside Look at a MOF in Action mof Researchers have recorded the first in situ electronic-structure observations of the adsorption of

  19. Recombination enhances HIV-1 envelope diversity by facilitating the

    Office of Scientific and Technical Information (OSTI)

    survival of latent genomic fragments in the plasma virus population (Journal Article) | DOE PAGES Recombination enhances HIV-1 envelope diversity by facilitating the survival of latent genomic fragments in the plasma virus population « Prev Next » Title: Recombination enhances HIV-1 envelope diversity by facilitating the survival of latent genomic fragments in the plasma virus population HIV-1 is subject to immune pressure exerted by the host, giving variants that escape the immune

  20. LOS ALAMOS, N.M., Nov. 19, 2013-Researchers at Los Alamos National Laboratory

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    virus spread and evolution studied through computer modeling November 19, 2013 LOS ALAMOS, N.M., Nov. 19, 2013-Researchers at Los Alamos National Laboratory are investigating the complex relationships between the spread of the HIV virus in a population (epidemiology) and the actual, rapid evolution of the virus (phylogenetics) within each patient's body. "We have developed novel ways of estimating epidemics dynamics such as who infected whom, and the true population incidence of infection

  1. Selective deposition of nanostructured ruthenium oxide using Tobacco mosaic

    Office of Scientific and Technical Information (OSTI)

    virus for micro-supercapacitors in solid Nafion electrolyte (Journal Article) | SciTech Connect Journal Article: Selective deposition of nanostructured ruthenium oxide using Tobacco mosaic virus for micro-supercapacitors in solid Nafion electrolyte Citation Details In-Document Search Title: Selective deposition of nanostructured ruthenium oxide using Tobacco mosaic virus for micro-supercapacitors in solid Nafion electrolyte Authors: Gnerlich, Markus ; Ben-Yoav, Hadar ; Culver, James ;

  2. Structure of the cleavage-activated prefusion form of the parainfluenza

    Office of Scientific and Technical Information (OSTI)

    virus 5 fusion protein (Journal Article) | SciTech Connect of the cleavage-activated prefusion form of the parainfluenza virus 5 fusion protein Citation Details In-Document Search Title: Structure of the cleavage-activated prefusion form of the parainfluenza virus 5 fusion protein Authors: Welch, Brett D. ; Liu, Yuanyuan ; Kors, Christopher A. ; Leser, George P. ; Jardetzky, Theodore S. ; Lamb, Robert A. [1] ; Stanford-MED) [2] + Show Author Affiliations NWU ( Publication Date: 2014-08-26

  3. Science On Tap - Phylogenetics and Epidemics

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    and the actual, rapid evolution of the virus (phylogenetics) within each patient's body. "We have developed novel ways of estimating epidemics dynamics such as who infected...

  4. LOS ALAMOS, N.M., Nov. 19, 2013-Researchers at Los Alamos National...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    and the actual, rapid evolution of the virus (phylogenetics) within each patient's body. "We have developed novel ways of estimating epidemics dynamics such as who infected...

  5. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    of Ligands Targeting a Novel Site on the Integrase Enzyme of Human Immunodeficiency Virus;8197;1 Wielens, Jerome ; Headey, Stephen J. ; Deadman, John J. ; Rhodes, David I. ;...

  6. Tailored Terahertz Pulses from a Laser-Modulated Electron Beam

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    viruses and atoms-scientists have the entire electromagnetic spectrum at their disposal: radio waves, microwaves, and infrared light below the visible spectrum, and ultraviolet...

  7. Broad Distribution of Energetically Important Contacts across...

    Office of Scientific and Technical Information (OSTI)

    Language: ENGLISH Subject: 59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; AFFINITY; AIDS VIRUS; DISTRIBUTION; HYPOTHESIS; PROTEINS Word Cloud More Like This Full Text ...

  8. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Hatch, Anson V. ; Singh, Anup K. ; Sommer, Gregory J. Abstract not provided. January 2008 A Novel Approach to Unknown Virus Identification in Clinical Samples. La Bauve, Elisa ; ...

  9. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Track Viral Evolution - A sensitive technique developed at the Laboratory can identify virus mutations that may jump frommore host to host; and (5) Data for Defense: New ...

  10. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... platforms for preclinical and field testing that utilize the assays developed in goal 1. We generated and characterized suitable primers for West Nile Virus RNA detection. ...

  11. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... sciences (2) basic biological sciences (2) hydrogen (2) acrolein (1) adducts (1) aids virus (1) animal cells (1) antibodies (1) arginine (1) biological radiation effects (1) ...

  12. Investigation of type-I interferon dysregulation by arenaviruses...

    Office of Scientific and Technical Information (OSTI)

    infection assays, molecular virology analysis of Arenavirus nucleoprotein structure-function, and development of computational tools to predict virus-host protein interactions. ...

  13. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... module, c) a dielectrophoresis virus filter module, d) an isotachophoresis nucleic acid filter module, e) a lyses module, and f) an isotachophoresis-based nucleic acid filter. ...

  14. Self-assembled Ni/TiO{sub 2} nanocomposite anodes synthesized...

    Office of Scientific and Technical Information (OSTI)

    Ni(core)TiOsub 2(shell) nanocomposite anodes were fabricated on three-dimensional, self-assembled nanotemplates of Tobacco mosaic virus using atomic layer deposition, exhibiting ...

  15. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    platforms for preclinical and field testing that utilize the assays developed in goal 1. We generated and characterized suitable primers for West Nile Virus RNA detection. ...

  16. The FELICIA bulletin board system and the IRBIS anonymous FTP server: Computer security information sources for the DOE community. CIAC-2302

    SciTech Connect (OSTI)

    Orvis, W.J.

    1993-11-03

    The Computer Incident Advisory Capability (CIAC) operates two information servers for the DOE community, FELICIA (formerly FELIX) and IRBIS. FELICIA is a computer Bulletin Board System (BBS) that can be accessed by telephone with a modem. IRBIS is an anonymous ftp server that can be accessed on the Internet. Both of these servers contain all of the publicly available CIAC, CERT, NIST, and DDN bulletins, virus descriptions, the VIRUS-L moderated virus bulletin board, copies of public domain and shareware virus- detection/protection software, and copies of useful public domain and shareware utility programs. This guide describes how to connect these systems and obtain files from them.

  17. "Title","Creator/Author","Publication Date","OSTI Identifier...

    Office of Scientific and Technical Information (OSTI)

    developed in goal 1. We generated and characterized suitable primers for West Nile Virus RNA detection. Both optical and electrochemical transduction technologies were...

  18. disease outbreak. Brozik, Susan Marie; Manginell, Ronald Paul...

    Office of Scientific and Technical Information (OSTI)

    developed in goal 1. We generated and characterized suitable primers for West Nile Virus RNA detection. Both optical and electrochemical transduction technologies were...

  19. TITLE AUTHORS SUBJECT SUBJECT RELATED DESCRIPTION PUBLISHER AVAILABILI...

    Office of Scientific and Technical Information (OSTI)

    assays developed in goal We generated and characterized suitable primers for West Nile Virus RNA detection Both optical and electrochemical transduction technologies were...

  20. ALSNews Vol. 338

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    aid in the eventual development of a universal vaccine, protecting against all types of influenza viruses and eliminating the guesswork that limits vaccine effectiveness. Read...

  1. CPL4001840-20151231100208

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    este mensaje, ni se responsabiliza de los posibles perjuicios de cualquier naturaleza derivados de la captura de datos, virus informaticos o manipulaciones efectuadas por terceros....

  2. 1

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Stopping executions, saving computers with new malware detection tool October 21, 2009 Virus detection takes a smarter turn with information- based approach Los Alamos, New Mexico,...

  3. Science and Technology Review December 2011 (Technical Report...

    Office of Scientific and Technical Information (OSTI)

    Track Viral Evolution - A sensitive technique developed at the Laboratory can identify virus mutations that may jump from host to host; and (5) Data for Defense: New Software...

  4. Modular microfluidic system for biological sample preparation...

    Office of Scientific and Technical Information (OSTI)

    filter module, b) a dielectrophoresis bacteria filter module, c) a dielectrophoresis virus filter module, d) an isotachophoresis nucleic acid filter module, e) a lyses module,...

  5. BSL Fact Sheet_r02_12-08-2005_keb.pub

    National Nuclear Security Administration (NNSA)

    virus, severe acute respiratory syndrome (SARS), monkeypox, and annual outbreaks of influenza. To control epidemics and protect the public health, medical researchers must...

  6. SEQUEDEX

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    diseases (whether arising from bacteria, parasites, or viruses; characterizing gut, oral and skin microbiomes of humans, livestock, and pets; metagenomics of soils, rivers,...

  7. Work with Biological Materials

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    cells, viruses), plant or soil samples (USDA quarantines), recombinant DNA, or blood-borne pathogen. Biological Use Authorization The great majority of biological work at...

  8. Calendar Year 2001 | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    of the Purchase of Protective Force Respirators April 5, 2001 Audit Report: IG-0500 Virus Protection Strategies and Cyber Security Incident Reporting April 3, 2001 Special...

  9. HIV evolution in early infection: selection pressures, patterns...

    Office of Scientific and Technical Information (OSTI)

    host environment and immune responses typically experienced by the newly transmitted virus. For example, sites that tend to evolve rapidly across multiple early-infection...

  10. Nanomaterial Composites for Next Generation Water Filters: Cooperative Research and Development Final Report, CRADA Number CRD-06-197

    SciTech Connect (OSTI)

    Ginley, D.

    2013-04-01

    Under this CRADA, the Parties will produce and test a composite filter element that will remove particles, bacteria and viruses to produce safe drinking water.

  11. Research deciphers HIV attack plan

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Korber. "Through this study we now better understand the biology that defines that resilience." Scientists get inside look at how AIDS virus grooms its assault team LOS ALAMOS,...

  12. Discovery and Preclinical Characterization of theCyclopropylindoloben...

    Office of Scientific and Technical Information (OSTI)

    clopropylindolobenzazepine BMS-791325, A Potent Allosteric Inhibitor of the Hepatitis C Virus NS5B Polymerase Citation Details In-Document Search Title: Discovery and Preclinical...

  13. News Item

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    protein can do - self-assemble into a precise structure that recognizes viruses and bacteria - but are more durable than natural molecules and can be stored without refrigeration. ...

  14. Relationships between HIV spread and evolution examined

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    material of the virus. The researchers aim to utilize the HIV genetic footprint in mathematical models to reconstruct accurately how epidemics spread. The model systems could be...

  15. 1

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    material of the virus. The researchers aim to utilize the HIV genetic footprint in mathematical models to reconstruct accurately how epidemics spread. The model systems could be...

  16. DOE Grant DEFG02-95ER25253 Final Report Development of Simulation...

    Office of Scientific and Technical Information (OSTI)

    ... has been conducted, in collaboration with Garcea, on developing non-kinetic models of papovaviruses, a class of animal viruses including some believed to cause cancer in humans. ...

  17. EA-1363: Finding of No Significant Impact

    Broader source: Energy.gov [DOE]

    Joint Environmental Assessment 2002-2006 of the California Department Of Food and Agriculture Curly Top Virus Control Program for Bureau Of Land Management and Department Of Energy

  18. STANFORD SYNCHROTRON RADIATION LIGHTSOURCE The Stanford Synchrotron...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    the very nature of bacteria and viruses, exposed how genetic mutations may cause diabetes, and mapped the structures of proteins for use in biology and medicine. Opportunities...

  19. Anti-influenza M2e antibody

    DOE Patents [OSTI]

    Bradbury, Andrew M.

    2013-04-16

    Humanized recombinant and monoclonal antibodies specific for the ectodomain of the influenza virus M2 ion channel protein are disclosed. The antibodies of the invention have anti-viral activity and may be useful as anti-viral therapeutics and/or prophylactic/vaccine agents for inhibiting influenza virus replication and for treating individuals infected with influenza.

  20. Anti-influenza M2e antibody

    DOE Patents [OSTI]

    Bradbury, Andrew M. (Santa Fe, NM)

    2011-12-20

    Humanized recombinant and monoclonal antibodies specific for the ectodomain of the influenza virus M2 ion channel protein are disclosed. The antibodies of the invention have anti-viral activity and may be useful as anti-viral therapeutics and/or prophylactic/vaccine agents for inhibiting influenza virus replication and for treating individuals infected with influenza.

  1. Viral chemotherapy. Volume 2

    SciTech Connect (OSTI)

    Shugar, D.

    1985-01-01

    This book contains seven chapters. Some of the chapter titles are: Molecular aspects of RNA tumor virus-induced carcinogenesis; Trifluorothymidine; Effects of antiviral nucleoside analogs on purine metabolism; Development of drug resistance and dependence in viruses; and Low molecular weight interferon inducers: Structure and biology.

  2. Three-Dimensional Reconstruction of the Giant Mimivirus Particle with an X-Ray Free-Electron Laser

    SciTech Connect (OSTI)

    Ekeberg, Tomas

    2015-05-26

    This dataset contains the diffraction patterns that were used for the first three-dimensional reconstruction of a virus using FEL data. The sample was the giant mimivirus particle, which is one of the largest known viruses with a diameter of 450 nm. The dataset consists of the 198 diffraction patterns that were used in the analysis.

  3. Detection of bioagents using a shear horizontal surface acoustic wave biosensor

    DOE Patents [OSTI]

    Larson, Richard S; Hjelle, Brian; Hall, Pam R; Brown, David C; Bisoffi, Marco; Brozik, Susan M; Branch, Darren W; Edwards, Thayne L; Wheeler, David

    2014-04-29

    A biosensor combining the sensitivity of surface acoustic waves (SAW) generated at a frequency of 325 MHz with the specificity provided by antibodies and other ligands for the detection of viral agents. In a preferred embodiment, a lithium tantalate based SAW transducer with silicon dioxide waveguide sensor platform featuring three test and one reference delay lines was used to adsorb antibodies directed against Coxsackie virus B4 or the negative-stranded category A bioagent Sin Nombre virus (SNV). Rapid detection of increasing concentrations of viral particles was linear over a range of order of magnitude for both viruses, and the sensor's selectivity for its target was not compromised by the presence of confounding Herpes Simplex virus type 1 The biosensor was able to delect SNV at doses lower than the load of virus typically found in a human patient suffering from hantavirus cardiopulmonary syndrome (HCPS).

  4. Economic and policy implications of pandemic influenza.

    SciTech Connect (OSTI)

    Smith, Braeton J.; Starks, Shirley J.; Loose, Verne W.; Brown, Theresa Jean; Warren, Drake E.; Vargas, Vanessa N.

    2010-03-01

    Pandemic influenza has become a serious global health concern; in response, governments around the world have allocated increasing funds to containment of public health threats from this disease. Pandemic influenza is also recognized to have serious economic implications, causing illness and absence that reduces worker productivity and economic output and, through mortality, robs nations of their most valuable assets - human resources. This paper reports two studies that investigate both the short- and long-term economic implications of a pandemic flu outbreak. Policy makers can use the growing number of economic impact estimates to decide how much to spend to combat the pandemic influenza outbreaks. Experts recognize that pandemic influenza has serious global economic implications. The illness causes absenteeism, reduced worker productivity, and therefore reduced economic output. This, combined with the associated mortality rate, robs nations of valuable human resources. Policy makers can use economic impact estimates to decide how much to spend to combat the pandemic influenza outbreaks. In this paper economists examine two studies which investigate both the short- and long-term economic implications of a pandemic influenza outbreak. Resulting policy implications are also discussed. The research uses the Regional Economic Modeling, Inc. (REMI) Policy Insight + Model. This model provides a dynamic, regional, North America Industrial Classification System (NAICS) industry-structured framework for forecasting. It is supported by a population dynamics model that is well-adapted to investigating macro-economic implications of pandemic influenza, including possible demand side effects. The studies reported in this paper exercise all of these capabilities.

  5. I Am Science - and So Can You!

    SciTech Connect (OSTI)

    DiChristina, Mariette

    2013-05-08

    Science is humanity’s best invention for getting at the truth about how things work (a.k.a. “basic research”) and solving problems (“applied”). I can even make a claim that most people are interested in science topics—they just don’t think of them as “science.” Consider how many of today’s top headlines have a critical science underpinning: energy supply, social change from digital innovations, efforts to treat cancer and other diseases, emerging infectious agents like bird flu, climate change, and so on. Clearly, a basic understanding about science is more vital than ever. At the same time, we see two trends: the collapse of traditional science journalism jobs as newspapers have cut thousands of positions and a greater access to—and a larger readership for—science-related materials than the world has ever known. Put another way, just when the public needs the Fourth Estate most, it’s instead drowning in a sea of 24/7 misinformation (a.k.a. “the Internet”). What’s a busy scientist to do to help engage the lay public? Glad you asked.

  6. Multiplex Degenerate Primer Design for Targeted Whole Genome Amplification of Many Viral Genomes

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Gardner, Shea N.; Jaing, Crystal J.; Elsheikh, Maher M.; Peña, José; Hysom, David A.; Borucki, Monica K.

    2014-01-01

    Background . Targeted enrichment improves coverage of highly mutable viruses at low concentration in complex samples. Degenerate primers that anneal to conserved regions can facilitate amplification of divergent, low concentration variants, even when the strain present is unknown. Results . A tool for designing multiplex sets of degenerate sequencing primers to tile overlapping amplicons across multiple whole genomes is described. The new script, run_tiled_primers, is part of the PriMux software. Primers were designed for each segment of South American hemorrhagic fever viruses, tick-borne encephalitis, Henipaviruses, Arenaviruses, Filoviruses, Crimean-Congo hemorrhagic fever virus, Rift Valley fever virus, and Japanese encephalitis virus.more » Each group is highly diverse with as little as 5% genome consensus. Primer sets were computationally checked for nontarget cross reactions against the NCBI nucleotide sequence database. Primers for murine hepatitis virus were demonstrated in the lab to specifically amplify selected genes from a laboratory cultured strain that had undergone extensive passage in vitro and in vivo. Conclusions . This software should help researchers design multiplex sets of primers for targeted whole genome enrichment prior to sequencing to obtain better coverage of low titer, divergent viruses. Applications include viral discovery from a complex background and improved sensitivity and coverage of rapidly evolving strains or variants in a gene family.« less

  7. Characterization of a novel insect-specific flavivirus from Brazil: Potential for inhibition of infection of arthropod cells with medically important flaviviruses.

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Kenney, Joan L.; Solberg, Owen D.; Langevin, Stanley A.; Brault, Aaron C.

    2014-01-12

    In the past decade, there has been an upsurge in the number of newly described insect-specific flaviviruses isolated pan-globally. We recently described the isolation of a novel flavivirus (tentatively designated ‘Nhumirim virus’; NHUV) that represents an example of a unique subset of apparently insect-specific viruses that phylogenetically affiliate with dual-host mosquito-borne flaviviruses despite appearing to be limited to replication in mosquito cells. We characterized the in vitro growth potential and 3' untranslated region (UTR) sequence homology with alternative flaviviruses, and evaluated the virus’s capacity to suppress replication of representative Culex spp.-vectored pathogenic flaviviruses in mosquito cells. Only mosquito cell linesmore » were found to support NHUV replication, further reinforcing the insect-specific phenotype of this virus. Analysis of the sequence and predicted RNA secondary structures of the 3' UTR indicated NHUV to be most similar to viruses within the yellow fever serogroup and Japanese encephalitis serogroup, and viruses in the tick-borne flavivirus clade. NHUV was found to share the fewest conserved sequence elements when compared with traditional insect-specific flaviviruses. This suggests that, despite apparently being insect specific, this virus probably diverged from an ancestral mosquito-borne flavivirus. Co-infection experiments indicated that prior or concurrent infection of mosquito cells with NHUV resulted in a significant reduction in virus production of West Nile virus (WNV), St Louis encephalitis virus (SLEV) and Japanese encephalitis virus. As a result, the inhibitory effect was most effective against WNV and SLEV with over a 106-fold and 104-fold reduction in peak titres, respectively.« less

  8. Decades of Discovery

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    9 6/1/2011 6.10 Putting a Virus to Practical Use A virus is usually viewed as a problem, but T7 turned out to be useful, even valuable. In 1982, Brookhaven National Laboratory scientists, led by biologist William Studier, finished determining the DNA sequence of T7, a bacteriophage (bacteria-eating virus) that had the longest DNA sequence then known. When T7 invades a host cell, it makes proteins that turn off the host genes and turn on T7 genes. Researchers correlated the genetic map with T7's

  9. Microsoft Word - 1-Cover DisclaimerTitle Blue Final.doc

    National Nuclear Security Administration (NNSA)

    Fire Marshal. The roadside areas that had the highest risk of wildland fires were in Areas 29 and 30 (Section 13.5). A West Nile Virus sampling program on the NTS continued in 2006. Biologists conducted 14 trapping sessions at 8 sites on the NTS. A total of 111 individuals representing 6 species was captured and analyzed. One Culiseta inornata mosquito tested positive for the virus, but the test result is suspected to be false. Six injured hawks from the NTS tested negative for the virus

  10. Investigation of the mode of binding of a novel series ofN-benzyl...

    Office of Scientific and Technical Information (OSTI)

    of the hepatitis C viral polymerase are described herein. These compounds bind to the hepatitis C virus non-structural protein 5B (NS5B), and co-crystal structures of select...

  11. Slide 1

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    for Hanford Advisory Board Health, Safety, and Environmental Protection Committee E.M. Bowers, RL A.R. Johnson, MSA J.M. Rodriguez, MSA June 15, 2010 2 West Nile Virus - Awareness...

  12. Structural Molecular Biology, SSRL

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    cellular sacs full of digestive enzymes that break down bacteria, viruses and worn-out cell parts for recycling. When this recycling process goes awry, it can cause rare metabolic...

  13. Rf2a and rf2b transcription factors

    DOE Patents [OSTI]

    Beachy, Roger N. (St. Louis, MO); Petruccelli, Silvana (La Plata, AR); Dai, Shunhong (St. Louis, MO)

    2007-10-02

    A method of activating the rice tungro bacilliform virus (RTBV) promoter in vivo is disclosed. The RTBV promoter is activated by exposure to at least one protein selected from the group consisting of Rf2a and Rf2b.

  14. Researchers Funded by the DOE "Genomes to Life" Program Achieve...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    in stitching together a genome of a phage, or a virus of bacteria. An article by Dr. ... the National Institutes of Health and the Department of Energy's Office of Science. ...

  15. JC3 Bulletin Archive | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    A vulnerability was reported in McAfee VirusScan Enterprise. February 27, 2013 V-100: Adobe Flash Player Bugs Let Remote Users Execute Arbitrary Code Several vulnerabilities were...

  16. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... These permuted enzymes are widespread in virus, pathogenic bacteria, and eukaryotes. We determined the crystal structure of a member of the YaeFYiiX-like family from Bacillus ...

  17. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Release from PD-1 inhibitory signaling revives 'exhausted' virus-specific T cells in chronic viral infections. Here we present the crystal structure of murine PD-1 in complex with ...

  18. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... (amino acids 91-346) that closely resemble the corresponding domains of vaccinia virus topoisomerase IB. The five amino acids of DraTopIB that comprise the catalytic pentad ...

  19. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Structure of a Dengue Virus Envelope Protein Late-Stage Fusion Intermediate Klein, Daryl E. ; Choi, Jason L. ; Harrison, Stephen C. ; CH-Boston) February 2013 Shape change in the ...

  20. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Innate immunity is our first line of defense against a pathogenic bacteria or virus. A comprehensive 'system-level' understanding of innate immunity pathways such as toll-like ...

  1. Search for: All records | DOE Patents

    Office of Scientific and Technical Information (OSTI)

    ... the cell walls or membrane of host cells one at a time so that a particular substance (e.g. a molecular tag, nucleic acid, bacteria, virus etc.) can be introduced into the cell. ...

  2. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    Everything41 Electronic Full Text0 Citations41 Multimedia0 Datasets0 Software0 Filter Results Filter by Subject crystal structure (11) aids virus (7) design (7) synthesis (7) ...

  3. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... ; Bevilacqua, Philip C. ; Golden, Barbara L. ; Penn) The hepatitis delta virus (HDV) ribozyme and HDV-like ribozymes are self-cleaving RNAs found throughout all kingdoms of life. ...

  4. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Hyuk-Soo ; Blobel, Gnter ; Ren, Yi mRNA export factor 1 (Rae1) and nucleoporin 98 (Nup98) are host cell targets for the matrix (M) protein of vesicular stomatitis virus (VSV). ...

  5. 'Let the phage do the work': Using the phage P22 coat protein structures as a framework to understand its folding and assembly mutants

    SciTech Connect (OSTI)

    Teschke, Carolyn M., E-mail: Teschke@uconn.ed [Departments of Molecular and Cell Biology, and Chemistry, 91 N. Eagleville Rd., U-3125, University of Connecticut, Storrs, CT 06269-3125 (United States); Parent, Kristin N. [Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA (United States)

    2010-06-05

    The amino acid sequence of viral capsid proteins contains information about their folding, structure and self-assembly processes. While some viruses assemble from small preformed oligomers of coat proteins, other viruses such as phage P22 and herpesvirus assemble from monomeric proteins (Fuller and King, 1980). The subunit assembly process is strictly controlled through protein:protein interactions such that icosahedral structures are formed with specific symmetries, rather than aberrant structures. dsDNA viruses commonly assemble by first forming a precursor capsid that serves as a DNA packaging machine. DNA packaging is accompanied by a conformational transition of the small precursor procapsid into a larger capsid for isometric viruses. Here we highlight the pseudo-atomic structures of phage P22 coat protein and rationalize several decades of data about P22 coat protein folding, assembly and maturation generated from a combination of genetics and biochemistry.

  6. CoverSheet

    Office of Scientific and Technical Information (OSTI)

    that would be inappropriate and ineffective. For example, it seems likely that anti-virus tools will be a required compo- nent of the cyber health report scorecard for desktop...

  7. Domain-level rocking motion within a polymerase that translocates...

    Office of Scientific and Technical Information (OSTI)

    nucleic acid An X-ray crystallographic structure is described for unliganded Vaccinia virus poly(A) polymerase monomer (VP55), showing the first domain-level structural isoforms...

  8. ALSNews Vol. 278

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    from spambots. You need JavaScript enabled to view it To date, the H5N1 avian influenza viruses, which are currently circulating in domestic and wild birds on three...

  9. Science Summary

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    has found structural similarity between last year's H1N1 strain and the 1918 influenza virus that also caused a pandemic. They used SSRL Beam Line 9-2 to solve the 3D...

  10. Validating Computer-Designed Proteins for Vaccines

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    apply to a variety of other vaccine targets, such as human immunodeficiency virus and influenza. Wanted: Dead or Computed As strange as it sounds, most vaccines are composed of...

  11. ORISE: Postdoctoral Research Experiences - Zaheer Ahmed

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    to train and research in different labs around the world including those in Hong Kong, Egypt, the United Kingdom, and Italy. "We were able to control the influenza virus in...

  12. Five Livermore and LANL Scientists Named "Most Influential Scientific...

    National Nuclear Security Administration (NNSA)

    of a multinational team whose work contributed to the understanding of the Hepatitis C virus and a possible cure. Bette Korber, LANL (top right) Korber's work focuses on the human...

  13. Environment/Health/Safety (EHS)

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    has been in the news. Measles is a highly contagious respiratory disease caused by a virus. It spreads through the air through coughing and sneezing. Measles can be spread days...

  14. LA-8318-MS Informal Report I

    Office of Scientific and Technical Information (OSTI)

    ... D. (E-3) 2-75 QUANTITATION OF CELL FUSION BY TWENTY-ONE STRAINS OF NEWCASTLE DISEASE VIRUS USING FLOW MICROFLUOROMETRY. J. GEN. VIROL., V.41. P.27-36. 1978. CRAM, L. SCOTT (H-10) ...

  15. Validating Computer-Designed Proteins for Vaccines

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Computed As strange as it sounds, most vaccines are composed of actual dead viruses and bacteria. The idea is that presenting a dead form of the pathogen will fake your body into...

  16. ALSNews Vol. 278

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    is being protected from spambots. You need JavaScript enabled to view it To date, the H5N1 avian influenza viruses, which are currently circulating in domestic and wild birds on...

  17. Microsoft Word - h1n1

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    N. Engl. J. Med. 361, 1945-1952 (2009) 4. Krause, J.C., et al. Naturally Occurring Human Monoclonal Antibodies Neutralize both 1918 and 2009 Pandemic Influenza A (H1N1) Viruses....

  18. Structural Basis of Pre-existing Immunity to the 2009 H1N1 Pandemic...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    N. Engl. J. Med. 361, 1945-1952 (2009) Krause, J.C., et al. Naturally Occurring Human Monoclonal Antibodies Neutralize both 1918 and 2009 Pandemic Influenza A (H1N1) Viruses....

  19. T-612: False Positive Detection Generic.dx!yxk in DAT 6329

    Broader source: Energy.gov [DOE]

    This issue can affect all McAfee anti-virus products utilizing this DAT, however it will manifest itself only on endpoints such as VirusScan. Spsgui.exe - This file is typically found only on workstations that have the SAP client installed. This file is loaded by the SAP client when it starts up and is used to send and receive faxes inside the SAP application.

  20. Vaccine to control the viral infection of fish

    DOE Patents [OSTI]

    Leong, Jo-Ann C.

    1994-10-11

    Subunit vaccines and their use for immunizing fish against infection by viruses are disclosed. In particular, plasmid pG8 is constructed by joining, with the plasmid pUC8, DNA which encodes the glycoprotein of infectious hematopoietic necrosis virus (IHNV). E. coli cells are transformed by pG8, whereby pure viral antigen is produced to provide a vaccine for the control of IHNV in fish.

  1. Vaccine to Control the Viral Infection of Fish.

    DOE Patents [OSTI]

    Leong, JoAnn Ching

    1994-10-11

    Subunit vaccines and their use for immunizing fish against infection by viruses are disclosed. In particular, plasmid pG8 is constructed by joining, with the plasmid pUC8, DNA which encodes the glycoprotein of infectious hematopoietic necrosis virus (IHNV). E. coli cells are transformed by pG8, whereby pure viral antigen is produced to provide a vaccine for the control of IHNV in fish. 10 figs.

  2. 1

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Computer modeling reveals how surprisingly potent hepatitis C drug works February 19, 2013 LOS ALAMOS, N.M., Feb. 19, 2013-A study by researchers from Los Alamos National Laboratory and a multinational team reveals how daclatasvir, a direct-acting antiviral agent in development for the treatment of hepatitis C virus (HCV), targets one of its proteins and causes the fastest viral decline ever seen with anti-HCV drugs - within 12 hours of treatment. Chronic infection with hepatitis C virus affects

  3. Antibody evolution could guide HIV vaccine development

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Antibody evolution could guide HIV vaccine development Antibody evolution could guide HIV vaccine development The antibody studied is called a broadly cross-reactive neutralizing antibody, and details of its generation could provide a blueprint for effective vaccination. April 4, 2013 Co-evolution of virus and antibody - The evolution of the viral protein (green) from 14 weeks through 100 weeks post-transmission is compared to the maturation of the human antibody. Co-evolution of virus and

  4. 1

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    is Zika now a threat? February 25, 2016 Why is Zika now a threat? Mostly innocuous and fairly unknown until a few weeks ago, the Zika virus is suddenly dominating the news. Under scrutiny is the virus's putative link with a congenital birth defect called microcephaly, which causes babies to be born with abnormally small heads and undeveloped brains. Read the full story at HuffPost Science

  5. Ig-0500.PDF

    Office of Environmental Management (EM)

    21 AUDIT REPORT VIRUS PROTECTION STRATEGIES AND CYBER SECURITY INCIDENT REPORTING U.S. DEPARTMENT OF ENERGY OFFICE OF INSPECTOR GENERAL OFFICE OF AUDIT SERVICES APRIL 2001 DOE/IG-0500 April 5, 2001 MEMORANDUM FOR THE SECRETARY FROM: Gregory H. Friedman (Signed) Inspector General SUBJECT: INFORMATION: Audit Report on "Virus Protection Strategies and Cyber Security Incident Reporting" BACKGROUND Information Technology (IT) plays an integral role in the programs and operations of the

  6. Construction and biological activities of the first infectious cDNA clones of the genus Foveavirus

    SciTech Connect (OSTI)

    Meng, Baozhong; Venkataraman, Srividhya; Li, Caihong; Wang, Weizhou; Dayan-Glick, Cathy; Mawassi, Munir

    2013-01-20

    Grapevine rupestris stem pitting-associated virus (GRSPaV, genus Foveavirus, family Betaflexiviridae) is one of the most prevalent viruses in grapevines and is associated with three distinct diseases: rupestris stem pitting, vein necrosis and Syrah decline. Little is known about the biology and pathological properties of GRSPaV. In this work, we engineered a full-length infectious cDNA clone for GRSPaV and a GFP-tagged variant, both under the transcriptional control of Cauliflower mosaic virus 35 S promoter. We demonstrated that these cDNA clones were infectious in grapevines and Nicotiana benthamiana through fluorescence microscopy, RT-PCR, Western blotting and immuno electron microscopy. Interestingly, GRSPaV does not cause systemic infection in four of the most commonly used herbaceous plants, even in the presence of the movement proteins of two other viruses which are known to complement numerous movement-defective viruses. These infectious clones are the first of members of Foveavirus which would allow further investigations into mechanisms governing different aspects of replication for GRSPaV and perhaps related viruses.

  7. Nowcasting influenza outbreaks using open-source media report.

    SciTech Connect (OSTI)

    Ray, Jaideep; Brownstein, John S.

    2013-02-01

    We construct and verify a statistical method to nowcast influenza activity from a time-series of the frequency of reports concerning influenza related topics. Such reports are published electronically by both public health organizations as well as newspapers/media sources, and thus can be harvested easily via web crawlers. Since media reports are timely, whereas reports from public health organization are delayed by at least two weeks, using timely, open-source data to compensate for the lag in %E2%80%9Cofficial%E2%80%9D reports can be useful. We use morbidity data from networks of sentinel physicians (both the Center of Disease Control's ILINet and France's Sentinelles network) as the gold standard of influenza-like illness (ILI) activity. The time-series of media reports is obtained from HealthMap (http://healthmap.org). We find that the time-series of media reports shows some correlation ( 0.5) with ILI activity; further, this can be leveraged into an autoregressive moving average model with exogenous inputs (ARMAX model) to nowcast ILI activity. We find that the ARMAX models have more predictive skill compared to autoregressive (AR) models fitted to ILI data i.e., it is possible to exploit the information content in the open-source data. We also find that when the open-source data are non-informative, the ARMAX models reproduce the performance of AR models. The statistical models are tested on data from the 2009 swine-flu outbreak as well as the mild 2011-2012 influenza season in the U.S.A.

  8. Generation and distribution of PAHs in the process of medical waste incineration

    SciTech Connect (OSTI)

    Chen, Ying; Zhao, Rongzhi; Xue, Jun; Li, Jinhui

    2013-05-15

    Highlights: ? PAHs generation and distribution features of medical waste incineration are studied. ? More PAHs were found in fly ash than that in bottom ash. ? The highest proportion of PAHs consisted of the seven most carcinogenic ones. ? Increase of free oxygen molecule and burning temperature promote PAHs degradation. ? There is a moderate positive correlation between total PCDD/Fs and total PAHs. - Abstract: After the deadly earthquake on May 12, 2008 in Wenchuan county of China, several different incineration approaches were used for medical waste disposal. This paper investigates the generation properties of polycyclic aromatic hydrocarbons (PAHs) during the incineration. Samples were collected from the bottom ash in an open burning slash site, surface soil at the open burning site, bottom ash from a simple incinerator, bottom ash generated from the municipal solid waste (MSW) incinerator used for medical waste disposal, and bottom ash and fly ash from an incinerator exclusively used for medical waste. The species of PAHs were analyzed, and the toxicity equivalency quantities (TEQs) of samples calculated. Analysis results indicate that the content of total PAHs in fly ash was 1.8 Ś 10{sup 3} times higher than that in bottom ash, and that the strongly carcinogenic PAHs with four or more rings accumulated sensitively in fly ash. The test results of samples gathered from open burning site demonstrate that Acenaphthylene (ACY), Acenaphthene (ACE), Fluorene (FLU), Phenanthrene (PHE), Anthracene (ANT) and other PAHs were inclined to migrate into surrounding environment along air and surface watershed corridors, while 4- to 6-ring PAHs accumulated more likely in soil. Being consistent with other studies, it has also been confirmed that increases in both free oxygen molecules and combustion temperatures could promote the decomposition of polycyclic PAHs. In addition, without the influence of combustion conditions, there is a positive correlation between total PCDD/Fs and total PAHs, although no such relationship has been found for TEQ.

  9. Structural Basis for a Switch in Receptor Binding Specificity of Two H5N1 Hemagglutinin Mutants

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Zhu, Xueyong; Viswanathan, Karthik; Raman, Rahul; Yu, Wenli; Sasisekharan, Ram; Wilson, Ian A.

    2015-11-01

    Avian H5N1 influenza viruses continue to spread in wild birds and domestic poultry with sporadic infection in humans. Receptor binding specificity changes are a prerequisite for H5N1 viruses and other zoonotic viruses to be transmitted among humans. Previous reported hemagglutinin (HA) mutants from ferret-transmissible H5N1 viruses of A/Viet Nam/1203/04 and A/Indonesia/5/05 showed slightly increased, but still very weak, binding to human receptors. From mutagenesis and glycan array studies, we previously identified two H5N1 HA mutants that could more effectively switch receptor specificity to human-like α2-6 linked sialosides with avidity comparable to wild-type H5 HA binding to avian-like α2-3 linked sialosides.more »Here, crystal structures of these two H5 HA mutants free and in complex with human and avian glycan receptor analogues reveal the structural basis for their preferential binding to human receptors. These findings suggest continuous surveillance should be maintained to monitor and assess human-to-human transmission potential of H5N1 viruses.« less

  10. Quantitative real-time single particle analysis of virions

    SciTech Connect (OSTI)

    Heider, Susanne; Metzner, Christoph

    2014-08-15

    Providing information about single virus particles has for a long time been mainly the domain of electron microscopy. More recently, technologies have been developed—or adapted from other fields, such as nanotechnology—to allow for the real-time quantification of physical virion particles, while supplying additional information such as particle diameter concomitantly. These technologies have progressed to the stage of commercialization increasing the speed of viral titer measurements from hours to minutes, thus providing a significant advantage for many aspects of virology research and biotechnology applications. Additional advantages lie in the broad spectrum of virus species that may be measured and the possibility to determine the ratio of infectious to total particles. A series of disadvantages remain associated with these technologies, such as a low specificity for viral particles. In this review we will discuss these technologies by comparing four systems for real-time single virus particle analysis and quantification. - Highlights: ‱ We introduce four methods for virus particle-based quantification of viruses. ‱ They allow for quantification of a wide range of samples in under an hour time. ‱ The additional measurement of size and zeta potential is possible for some.

  11. Hematology, Parasitology, and Serology of Free-Ranging Coyotes (Canis latrans) from South Carolina.

    SciTech Connect (OSTI)

    Miller, Debra, Lee; Schrecengost, Joshua; Merrill, Anita; Kilgo, John; Ray, H., Scott; Karl V. Miller, Karl, V.; Baldwin, Charles, A.

    2009-07-01

    ABSTRACT: Blood and feces were collected from 34 adult (19 males, 15 females) and seven juvenile (three males, one female, three not reported) free-ranging coyotes (Canis latrans) on the US Department of Energy’s Savannah River Site (South Carolina, USA). Significant (P,0.05) hematologic differences by sex were noted for red blood cell counts, hemoglobin, and hematocrit. Biochemical differences by sex occurred only for albumen (P,0.05). Twentyone adults were antibody positive for at least one of four viruses: canine adenovirus type 1 (CAV-1; 68%), West Nile virus (WNV; 60%), Eastern equine encephalitis virus (EEEV; 38%), and Canine distemper virus (CDV; 15%). Of the seven Leptospira serovars tested for, seven (25%) of 28 adults were positive for one or more of five serovars: Pomona, Grippotyphosa, Icterohaemorrhagiae, Bratislava, and Autumnalis. Three (43%) of seven juveniles had seropositivity for a virus, one each for CDV, CAV-1, and WNV. No juveniles were seropositive for EEEV or any of the seven Leptospira serovars. Blood smears of 12 adults were positive for Dirofilaria immitis microfilaria, but blood smears from all juveniles were negative. Parvovirus was identified by electron microscopy from the feces of one adult. Ancylostoma spp., Trichuris spp., and Isospora spp. were observed in fecal samples. These data may aid in understanding the role of coyotes in disease ecology.

  12. Use of Cre/loxP recombination to swap cell binding motifs on the adenoviral capsid protein IX

    SciTech Connect (OSTI)

    Poulin, Kathy L.; Tong, Grace; Vorobyova, Olga; Pool, Madeline; Kothary, Rashmi; Parks, Robin J.

    2011-11-25

    We used Cre/loxP recombination to swap targeting ligands present on the adenoviral capsid protein IX (pIX). A loxP-flanked sequence encoding poly-lysine (pK-binds heparan sulfate proteoglycans) was engineered onto the 3'-terminus of pIX, and the resulting fusion protein allowed for routine virus propagation. Growth of this virus on Cre-expressing cells removed the pK coding sequence, generating virus that could only infect through alternative ligands, such as a tyrosine kinase receptor A (TrkA)-binding motif engineered into the capsid fibre protein for enhanced infection of neuronal cells. We used a similar approach to swap the pK motif on pIX for a sequence encoding a single-domain antibody directed towards CD66c for targeted infection of cancer cells; Cre-mediated removal of the pK-coding sequence simultaneously placed the single-domain antibody coding sequence in frame with pIX. Thus, we have developed a simple method to propagate virus lacking native viral tropism but containing cell-specific binding ligands. - Highlights: > We describe a method to grow virus lacking native tropism but containing novel cell-binding ligands. > Cre/loxP recombination was used to modify the adenovirus genome. > A targeting ligand present on capsid protein IX was removed or replaced using recombination. > Cre-loxP was also used to 'swap' the identity of the targeting ligand present on pIX.

  13. Final Technical Report: Viral Infection of Subsurface Microorganisms and Metal/Radionuclide Transport

    SciTech Connect (OSTI)

    Weber, Karrie A.; Bender, Kelly S.; Li, Yusong

    2013-09-28

    Microbially mediated metabolisms have been identified as a significant factor either directly or indirectly impacting the fate and transport of heavy metal/radionuclide contaminants. To date microorganisms have been isolated from contaminated environments. Examination of annotated finished genome sequences of many of these subsurface isolates from DOE sites, revealed evidence of prior viral infection. To date the role that viruses play influencing microbial mortality and the resulting community structure which directly influences biogeochemical cycling in soils and sedimentary environments remains poorly understood. The objective of this exploratory study was to investigate the role of viral infection of subsurface bacteria and the formation of contaminant-bearing viral particles. This objective was approached by examining the following working hypotheses: (i) subsurface microorganisms are susceptible to viral infections by the indigenous subsurface viral community, and (ii) viral surfaces will adsorb heavy metals and radionuclides. Our results have addressed basic research needed to accomplish the BER Long Term Measure to provide sufficient scientific understanding such that DOE sites would be able to incorporate coupled physical, chemical and biological processes into decision making for environmental remediation or natural attenuation and long-term stewardship by establishing viral-microbial relationships on the subsequent fate and transport of heavy metals and radionuclides. Here we demonstrated that viruses play a significant role in microbial mortality and community structure in terrestrial subsurface sedimentary systems. The production of viral-like particles within subsurface sediments in response to biostimulation with dissolved organic carbon and a terminal electron acceptor resulted in the production of viral-like particles. Organic carbon alone did not result in significant viral production and required the addition of a terminal electron acceptor (nitrate), indicating that nutrients are not limiting viral production, but rather substrates that can be converted into energy for host metabolism. Our results also revealed that cell abundance was not correlated to the mineralization of organic carbon, but rather viruses were positively correlated with carbon mineralization. This is a result of viral-mediated cell lysis and demonstrates that viruses are sensitive indicators of microbial activity. Viruses as an indicator of microbial activity was not unique to batch culture studies as results obtained from an in situ field experiment conducted at the DOE Old Rifle Field site. This study revealed that viral abundance increased in response to the injection of oxygenated groundwater and influx of dissolved organic carbon whereas cell abundance changes were minimal. However, the extent to which viral-mediated cell lysis alters organic matter pools subsequently influencing microbial community structure and biogeochemical function remains a critical question in subsurface biogeochemical cycling. The production of significant numbers of viruses in groundwater has implications for nanoparticulate metal as well as carbon transport in groundwater. We have demonstrated that the virus surface is reactive and will adsorb heavy metals. Thus viruses can promote colloidal contaminant mobility. Interestingly, the presence of heavy metals has a positive effect on infectivity of the phage, increasing phage infection which could lead to further production of viruses. Together, the results indicate that the sorption of metals to the surface of viruses could not only contribute to nanoparticulate metal as well as carbon transport but could also enhance infectivity further contributing to cell lysis which could subsequently influence biogeochemical cycling. As more viruses infect host microbial populations the high concentration of metals would enhance infection, resulting in cell lysis, and decreasing the metabolically active host population while yielding greater numbers of viruses capable of transporting contaminats. Additional studie

  14. Reduced expression of Autographa californica nucleopolyhedrovirus ORF34, an essential gene, enhances heterologous gene expression

    SciTech Connect (OSTI)

    Salem, Tamer Z.; Department of Microbial Molecular Biology, AGERI, Agricultural Research Center, Giza 12619; Division of Biomedical Sciences, Zewail University, Zewail City of Science and Technology, Giza 12588 ; Zhang, Fengrui; Thiem, Suzanne M.

    2013-01-20

    Autographa californica multiple nucleopolyhedrovirus ORF34 is part of a transcriptional unit that includes ORF32, encoding a viral fibroblast growth factor (FGF) and ORF33. We identified ORF34 as a candidate for deletion to improve protein expression in the baculovirus expression system based on enhanced reporter gene expression in an RNAi screen of virus genes. However, ORF34 was shown to be an essential gene. To explore ORF34 function, deletion (KO34) and rescue bacmids were constructed and characterized. Infection did not spread from primary KO34 transfected cells and supernatants from KO34 transfected cells could not infect fresh Sf21 cells whereas the supernatant from the rescue bacmids transfection could recover the infection. In addition, budded viruses were not observed in KO34 transfected cells by electron microscopy, nor were viral proteins detected from the transfection supernatants by western blots. These demonstrate that ORF34 is an essential gene with a possible role in infectious virus production.

  15. Evaluation of an Experimental Re-introduction of Sockeye Salmon into Skaha Lake; Year 2 of 3, 2001 Technical Report.

    SciTech Connect (OSTI)

    Fisher, Christopher; Machin, Deanna; Wright, Howie

    2002-04-01

    This report summarizes the findings from YEAR 2 of a three-year disease risk assessment. The Okanagan Nation Fisheries Commission (ONFC) and the Colville Confederated Tribes (CCT) are investigating the risks involved in re-introducing sockeye salmon into Skaha Lake, part of their historical range (Ernst and Vedan 2000). The disease risk assessment compares the disease and infection status of fish above and below McIntyre Dam (the present limit of sockeye migration). The disease agents identified that are of a particular concern are: infectious pancreatic necrosis virus (IPNV), infectious haematopoietic necrosis virus type 2 (IHNV type2), erythrocytic inclusion body syndrome virus (EIBSV), the whirling disease agent (Myxobolus cerebralis), and the ceratomyxosis agent (Ceratomyxa shasta).

  16. Structure of the uncleaved ectodomain of the paramyxovirus (hPIV3) fusion protein

    SciTech Connect (OSTI)

    Yin, Hsien-Sheng; Paterson, Reay G.; Wen, Xiaolin; Lamb, Robert A.; Jardetzky, Theodore S. (NWU)

    2010-03-08

    Class I viral fusion proteins share common mechanistic and structural features but little sequence similarity. Structural insights into the protein conformational changes associated with membrane fusion are based largely on studies of the influenza virus hemagglutinin in pre- and postfusion conformations. Here, we present the crystal structure of the secreted, uncleaved ectodomain of the paramyxovirus, human parainfluenza virus 3 fusion (F) protein, a member of the class I viral fusion protein group. The secreted human parainfluenza virus 3 F forms a trimer with distinct head, neck, and stalk regions. Unexpectedly, the structure reveals a six-helix bundle associated with the postfusion form of F, suggesting that the anchor-minus ectodomain adopts a conformation largely similar to the postfusion state. The transmembrane anchor domains of F may therefore profoundly influence the folding energetics that establish and maintain a metastable, prefusion state.

  17. Palmitoylation of SARS-CoV S protein is necessary for partitioning into detergent-resistant membranes and cell-cell fusion but not interaction with M protein

    SciTech Connect (OSTI)

    McBride, Corrin E.; Machamer, Carolyn E.

    2010-09-15

    Coronaviruses are enveloped RNA viruses that generally cause mild disease in humans. However, the recently emerged coronavirus that caused severe acute respiratory syndrome (SARS-CoV) is the most pathogenic human coronavirus discovered to date. The SARS-CoV spike (S) protein mediates virus entry by binding cellular receptors and inducing fusion between the viral envelope and the host cell membrane. Coronavirus S proteins are palmitoylated, which may affect function. Here, we created a non-palmitoylated SARS-CoV S protein by mutating all nine cytoplasmic cysteine residues. Palmitoylation of SARS-CoV S was required for partitioning into detergent-resistant membranes and for cell-cell fusion. Surprisingly, however, palmitoylation of S was not required for interaction with SARS-CoV M protein. This contrasts with the requirement for palmitoylation of mouse hepatitis virus S protein for interaction with M protein and may point to important differences in assembly and infectivity of these two coronaviruses.

  18. Radioimmunoassays of hidden viral antigens

    SciTech Connect (OSTI)

    Neurath, A.R. (Lindsley F. Kimbell Research Inst., New York, NY); Strick, N.; Baker, L.; Krugman, S.

    1982-07-01

    Antigens corresponding to infectious agents may be present in biological specimens only in a cryptic form bound to antibodies and, thus, may elude detection. We describe a solid-phase technique for separation of antigens from antibodies. Immune complexes are precipitated from serum by polyethylene glycol, dissociated with NaSCN, and adsorbed onto nitrocellulose or polystyrene supports. Antigens remain topographically separated from antibodies after removal of NaSCN and can be detected with radiolabeled antibodies. Genomes from viruses immobilized on nitrocellulose can be identified by nucleic acid hybridization. Nanogram quantities of sequestered hepatitis B surface and core antigens and picogram amounts of hepatitis B virus DNA were detected. Antibody-bound adenovirus, herpesvirus, and measles virus antigens were discerned by the procedure.

  19. Analysis of sensitivity and rapid hybridization of a multiplexed Microbial Detection Microarray

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Thissen, James B.; McLoughlin, Kevin; Gardner, Shea; Gu, Pauline; Mabery, Shalini; Slezak, Tom; Jaing, Crystal

    2014-06-01

    Microarrays have proven to be useful in rapid detection of many viruses and bacteria. Pathogen detection microarrays have been used to diagnose viral and bacterial infections in clinical samples and to evaluate the safety of biological drug materials. A multiplexed version of the Lawrence Livermore Microbial Detection Array (LLMDA) was developed and evaluated with minimum detectable concentrations for pure unamplified DNA viruses, along with mixtures of viral and bacterial DNA subjected to different whole genome amplification protocols. In addition the performance of the array was tested when hybridization time was reduced from 17 h to 1 h. The LLMDA wasmore » able to detect unamplified vaccinia virus DNA at a concentration of 14 fM, or 100,000 genome copies in 12 ΌL of sample. With amplification, positive identification was made with only 100 genome copies of input material. When tested against human stool samples from patients with acute gastroenteritis, the microarray detected common gastroenteritis viral and bacterial infections such as rotavirus and E. coli. Accurate detection was found but with a 4-fold drop in sensitivity for a 1 h compared to a 17 h hybridization. The array detected 2 ng (equivalent concentration of 15.6 fM) of labeled DNA from a virus with 1 h hybridization without any amplification, and was able to identify the components of a mixture of viruses and bacteria at species and in some cases strain level resolution. Sensitivity improved by three orders of magnitude with random whole genome amplification prior to hybridization; for instance, the array detected a DNA virus with only 20 fg or 100 genome copies as input. This multiplexed microarray is an efficient tool to analyze clinical and environmental samples for the presence of multiple viral and bacterial pathogens rapidly.« less

  20. Universal Serial Bus Architecture for Removable Media (USB-ARM)

    Energy Science and Technology Software Center (OSTI)

    2011-03-09

    USB-ARM creates operating system drivers which sit between removable media and the user and applications. The drivers isolate the media and submit the contents of the media to a virtual machine containing an entire scanning system. This scanning system may include traditional anti-virus, but also allows more detailed analysis of files, including dynamic run-time analysis, helping to prevent “zero-day” threats not already identified in anti-virus signatures. Once cleared, the media is presented to the operatingmore »system, at which point it becomes available to users and applications.« less

  1. New insights into HIV-1 vaccine design

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    New insights into HIV-1 vaccine design New insights into HIV-1 vaccine design Scientists have created a computational model that could change the way that researchers look at possibilities for an HIV-1 vaccine. September 17, 2015 An HIV virus attacking a T cell An HIV virus attacking a T cell Contact Los Alamos National Laboratory Nick Njegomir Communications Office (505) 665-9394 Email "An effective HIV-1 vaccine has proven elusive, partly due to the difficulty of causing an immune

  2. Link Alpha V

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    v A B C D E F G H I J K L M N O P Q R S T V W Y Z Filter by alpha... A B C D E F G H I J K L M N O P Q R S T U V W Y Z Vacation Policy Vanpool Commuting Program for Employees Vehicle Accident Report Vehicles: Information on Parking at the Lab Video Conferencing & Video Streaming services Video Conferencing Cart Video: Streaming Video Virus (computer virus) Protection & Software Visa and Immigration Services Vision Care Plan (UC Vision Plan) Visitor Information Visitor Pass Request

  3. Role of a reducing environment in disassembly of the herpesvirus tegument

    SciTech Connect (OSTI)

    Newcomb, William W.; Jones, Lisa M.; Dee, Alexander; Chaudhry, Farid; Brown, Jay C.

    2012-09-15

    Initiation of infection by herpes family viruses involves a step in which most of the virus tegument becomes detached from the capsid. Detachment takes place in the host cell cytosol near the virus entry site and it is followed by dispersal of tegument proteins and disappearance of the tegument as a distinct entity. Here we describe the results of experiments designed to test the idea that the reducing environment of the cytosol may contribute to tegument detachment and disassembly. Non-ionic detergent was used to remove the membrane of purified herpes simplex virus under control and reducing conditions. The effects on the tegument were then examined by SDS-PAGE and electron microscopy. Protein analysis demonstrated that most major tegument proteins were removed under both oxidizing and reducing conditions except for UL49 which required a reducing environment. It is proposed therefore that the reducing conditions in the cytosol are involved in removal of UL49 protein. Electron microscopic analysis revealed that capsids produced under oxidizing conditions contained a coating of protein that was absent in reduced virions and which correlated uniquely with the presence of UL49. This capsid-associated layer is suggested to be the location of UL49 in the extracted virion.

  4. Human retroviruses and AIDS 1994

    SciTech Connect (OSTI)

    Myers, G.; Korber, B.; Wain-Hobson, S.; Jeang, Kuan-Teh; Henderson, L.E.; Pavlakis, G.N.

    1995-01-01

    This compendium, including accompanying floppy diskettes, is the result of an effort to compile and rapidly publish all relevant molecular data concerning the human immunodeficiency viruses (HIV) and related retroviruses. The scope of the compendium and database is best summarized by the five parts it comprises: (I) Nucleic Acid Alignments and Sequences; (II) Amino Acid Alignments; (III) Analysis; (IV) Related Sequences; (V) Database communications.

  5. Modular microfluidic system for biological sample preparation

    DOE Patents [OSTI]

    Rose, Klint A.; Mariella, Jr., Raymond P.; Bailey, Christopher G.; Ness, Kevin Dean

    2015-09-29

    A reconfigurable modular microfluidic system for preparation of a biological sample including a series of reconfigurable modules for automated sample preparation adapted to selectively include a) a microfluidic acoustic focusing filter module, b) a dielectrophoresis bacteria filter module, c) a dielectrophoresis virus filter module, d) an isotachophoresis nucleic acid filter module, e) a lyses module, and f) an isotachophoresis-based nucleic acid filter.

  6. Three-dimensional colorimetric assay assemblies

    DOE Patents [OSTI]

    Charych, Deborah (Albany, CA); Reichert, Anke (Albany, CA)

    2001-01-01

    A direct assay is described using novel three-dimensional polymeric assemblies which change from a blue to red color when exposed to an analyte, in one case a flue virus. The assemblies are typically in the form of liposomes which can be maintained in a suspension, and show great intensity in their color changes. Their method of production is also described.

  7. Airborne spread of foot-and-mouth disease - model intercomparison

    SciTech Connect (OSTI)

    Gloster, J; Jones, A; Redington, A; Burgin, L; Sorensen, J H; Turner, R; Dillon, M; Hullinger, P; Simpson, M; Astrup, P; Garner, G; Stewart, P; D'Amours, R; Sellers, R; Paton, D

    2008-09-04

    Foot-and-mouth disease is a highly infectious vesicular disease of cloven-hoofed animals caused by foot-and-mouth disease virus. It spreads by direct contact between animals, by animal products (milk, meat and semen), by mechanical transfer on people or fomites and by the airborne route - with the relative importance of each mechanism depending on the particular outbreak characteristics. Over the years a number of workers have developed or adapted atmospheric dispersion models to assess the risk of foot-and-mouth disease virus spread through the air. Six of these models were compared at a workshop hosted by the Institute for Animal Health/Met Office during 2008. A number of key issues emerged from the workshop and subsequent modelling work: (1) in general all of the models predicted similar directions for 'at risk' livestock with much of the remaining differences strongly related to differences in the meteorological data used; (2) determination of an accurate sequence of events is highly important, especially if the meteorological conditions vary substantially during the virus emission period; and (3) differences in assumptions made about virus release, environmental fate, and subsequent infection can substantially modify the size and location of the downwind risk area. Close relationships have now been established between participants, which in the event of an outbreak of disease could be readily activated to supply advice or modelling support.

  8. Superhydrophobic surfaces

    DOE Patents [OSTI]

    Wang, Evelyn N; McCarthy, Matthew; Enright, Ryan; Culver, James N; Gerasopoulos, Konstantinos; Ghodssi, Reza

    2015-03-24

    Surfaces having a hierarchical structure--having features of both microscale and nanoscale dimensions--can exhibit superhydrophobic properties and advantageous condensation and heat transfer properties. The hierarchical surfaces can be fabricated using biological nanostructures, such as viruses as a self-assembled nanoscale template.

  9. Appreciating HIV-1 diversity: subtypic differences in ENV

    SciTech Connect (OSTI)

    Gnanakaran, S; Shen, Tongye; Lynch, Rebecca M; Derdeyn, Cynthia A

    2008-01-01

    Human immunodeficiency virus type 1 (HIV-1) group M is responsible for the current AIDS pandemic and exhibits exceedingly high levels of viral genetic diversity around the world, necessitating categorization of viruses into distinct lineages, or subtypes. These subtypes can differ by around 35% in the envelope (Env) glycoproteins of the virus, which are displayed on the surface of the virion and are targets for both neutralizing antibody and cell-mediated immune responses. This diversity reflects the remarkable ability of the virus to adapt to selective pressures, the bulk of which is applied by the host immune response, and represents a serious obstacle for developing an effective vaccine with broad coverage. Thus, it is important to understand the underlying biological consequences of inter-subtype diversity. Recent studies have revealed that the HIV-1 subtypes exhibit phenotypic differences that result from subtle differences in Env structure, particularly within the highly immunogenic V3 domain, which participates directly in viral entry. This review will therefore explore current research that describes subtypic differences in Env at the genetic and phenotypic level, focusing in particular on V3, and highlighting recent discoveries about the unique features of subtype C Env, which is the most prevalent subtype globally.

  10. Reversibly immobilized biological materials in monolayer films on electrodes

    DOE Patents [OSTI]

    Weaver, Paul F. (Golden, CO); Frank, Arthur J. (Lakewood, CO)

    1993-01-01

    Methods and techniques are described for reversibly binding charged biological particles in a fluid medium to an electrode surface. The methods are useful in a variety of applications. The biological materials may include microbes, proteins, and viruses. The electrode surface may consist of reversibly electroactive materials such as polyvinylferrocene, silicon-linked ferrocene or quinone.

  11. Science Headlines

    Office of Science (SC) Website

    -0500 12B69234-E106-461C-B008-1A4F342D3F6Dhttp:1.usa.gov20feQ3S A Respiratory Virus Provides Clues to Possible Treatments Purdue University researchers, working at the...

  12. News

    Office of Science (SC) Website

    glaciers. 12B69234-E106-461C-B008-1A4F342D3F6Dhttp:1.usa.gov20feQ3S A Respiratory Virus Provides Clues to Possible Treatments Purdue University researchers, working at the...

  13. Reversibly immobilized biological materials in monolayer films on electrodes

    DOE Patents [OSTI]

    Weaver, P.F.; Frank, A.J.

    1993-05-04

    Methods and techniques are described for reversibly binding charged biological particles in a fluid medium to an electrode surface. The methods are useful in a variety of applications. The biological materials may include microbes, proteins, and viruses. The electrode surface may consist of reversibly electroactive materials such as polyvinylferrocene, silicon-linked ferrocene or quinone.

  14. Physicochemical stability and inactivation of human and simian rotaviruses

    SciTech Connect (OSTI)

    Meng, Z.D.; Birch, C.; Heath, R.; Gust, I.

    1987-04-01

    The effects of various physical and chemical treatments on the stability of a human serotype 1 rotavirus and simian agent 11 (SA11) were compared by using a fluorescence focus assay. The infectivity of both strains was retained after storage at room temperature for 14 days, 4 degree C for 22 days, and -20 degree C for 32 days; lyophilization; and treatment at pH 3 to 11. Both viruses were inactivated at pH 12, as was the human virus at pH 2, although this pH resulted in only partial inactivation of SA11. The human virus also appeared to be more sensitive than SA11 to the action of ether and chloroform. The infectivity of both viruses was lost after UV irradiation for 15 min and after treatment with 8% formaldehyde for 5 min, 70% (vol/vol) ethanol for 30 min, and 2% lysol, 2% phenol, and 1% H/sub 2/O/sub 2/ for 1 h each.

  15. Sialic acid-dependent cell entry of human enterovirus D68

    SciTech Connect (OSTI)

    Liu, Yue; Sheng, Ju; Baggen, Jim; Meng, Geng; Xiao, Chuan; Thibaut, Hendrik J.; van Kuppeveld, Frank J. M.; Rossmann, Michael G.

    2015-11-13

    Human enterovirus D68 (EV-D68) is a causative agent of childhood respiratory diseases and has now emerged as a global public health threat. Nevertheless, knowledge of the tissue tropism and pathogenesis of EV-D68 has been hindered by a lack of studies on the receptor-mediated EV-D68 entry into host cells. Here we demonstrate that cell surface sialic acid is essential for EV-D68 to bind to and infect susceptible cells. Crystal structures of EV-D68 in complex with sialylated glycan receptor analogues show that they bind into the ‘canyon’ on the virus surface. The sialic acid receptor induces a cascade of conformational changes in the virus to eject a fatty-acid-like molecule that regulates the stability of the virus. Furthermore, virus binding to a sialic acid receptor and to immunoglobulin-like receptors used by most other enteroviruses share a conserved mechanism for priming viral uncoating and facilitating cell entry.

  16. Forensic Proteomics of Poxvirus Production

    SciTech Connect (OSTI)

    Wunschel, David S.; Tulman, Edan; Engelmann, Heather E.; Clowers, Brian H.; Geary, Steven J.; Robinson, Aaron C.; Liao, Xiaofen

    2013-08-27

    The field of microbial forensics has recently sought to develop methods to discern biological signatures to indicate production methods for biological agents. Viral agents have received less attention to date. Their obligate propagation in living cells makes purification from cellular material a challenge. This leads to potential carryover of protein-rich signature of their production system. Here we have explored a proteomic analysis of Vaccinia virus as a model poxvirus system in which to compare samples of virus propagated in different cell lines and subjected to different purification schemes. The proteomic data sets indicated viral, host cell and culture medium proteins, and several layers of data analysis were applied to build confidence in the peptide identification and capture information on the taxonomic utility of each. The analysis showed clear shifts in protein profiles with virus purification, with successive gradient purification steps showing different levels of viral protein enrichment. Peptides from cellular proteins, including those present in purified virus preparations, provided signatures which enabled discrimination of cell line substrates, including distinguishing between cells derived from different primate species. The ability to discern multiple aspects of viral production demonstrates the potential value of proteomic analysis as tool for microbial forensics.

  17. Sialic acid-dependent cell entry of human enterovirus D68

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Liu, Yue; Sheng, Ju; Baggen, Jim; Meng, Geng; Xiao, Chuan; Thibaut, Hendrik J.; van Kuppeveld, Frank J. M.; Rossmann, Michael G.

    2015-11-13

    Human enterovirus D68 (EV-D68) is a causative agent of childhood respiratory diseases and has now emerged as a global public health threat. Nevertheless, knowledge of the tissue tropism and pathogenesis of EV-D68 has been hindered by a lack of studies on the receptor-mediated EV-D68 entry into host cells. Here we demonstrate that cell surface sialic acid is essential for EV-D68 to bind to and infect susceptible cells. Crystal structures of EV-D68 in complex with sialylated glycan receptor analogues show that they bind into the ‘canyon’ on the virus surface. The sialic acid receptor induces a cascade of conformational changes inmore » the virus to eject a fatty-acid-like molecule that regulates the stability of the virus. Furthermore, virus binding to a sialic acid receptor and to immunoglobulin-like receptors used by most other enteroviruses share a conserved mechanism for priming viral uncoating and facilitating cell entry.« less

  18. Programmed cell death

    SciTech Connect (OSTI)

    1995-12-31

    The purpose of this conference to provide a multidisciplinary forum for exchange of state-of-the-art information on the role programmed cell death plays in normal development and homeostasis of many organisms. This volume contains abstracts of papers in the following areas: invertebrate development; immunology/neurology; bcl-2 family; biochemistry; programmed cell death in viruses; oncogenesis; vertebrate development; and diseases.

  19. QER- Comment of Petr Gladkov

    Broader source: Energy.gov [DOE]

    We decided all questions ENVIRONMENTALLY CLEAN energy the future of humanity official site ET Energy Corp: http://www.etenergycorp.com/ not official site ET Energy Corp. - For more advanced understanding and a deep dive into the essence of the proposed technologies: https://sites.google.com/site/scisyhpphysicspg1/ This email is free from viruses and malware because avast! Antivirus protection is active.

  20. Mathematical Modeling of Hepatitis C Prevalence Reduction with Antiviral Treatment Scale-Up in Persons Who Inject Drugs in Metropolitan Chicago

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Echevarria, Desarae; Gutfraind, Alexander; Boodram, Basmattee; Major, Marian; Del Valle, Sara; Cotler, Scott J.; Dahari, Harel

    2015-08-21

    New direct-acting antivirals (DAAs) provide an opportunity to combat hepatitis C virus (HCV) infection in persons who inject drugs (PWID). Here we use a mathematical model to predict the impact of a DAA-treatment scale-up on HCV prevalence among PWID and the estimated cost in metropolitan Chicago.

  1. Exploring Viral Genomics at Lawrence Livermore National Laboratory

    SciTech Connect (OSTI)

    Kilpatrick, K; Hiddessen, A

    2007-08-22

    This summer I had the privilege of working at Lawrence Livermore National Laboratory under the Nonproliferation, Homeland and International Security Directorate in the Chemical and Biological Countermeasures Division. I worked exclusively on the Viral Identification and Characterization Initiative (VICI) project focusing on the development of multiplexed polymerase chain reaction (PCR) assays. The goal of VICI is to combine several disciplines such as molecular biology, microfluidics, and bioinformatics in order to detect viruses and identify them in order to effectively and quickly counter infectious disease, natural or engineered. The difficulty in such a countermeasure is that little is known about viral diversity due to the ever changing nature of these organisms. In response, VICI is developing a new microfluidic bioanalytical platform to detect known and unknown viruses by analyzing every virus in a sample by isolating them into picoliter sized droplets on a microchip and individually analyzing them. The sample will be injected into a channel of oil to form droplets that will contain viral nucleic acids that will be amplified using PCR. The multiplexed PCR assay will produce a series of amplicons for a particular virus genome that provides an identifying signature. A device will then detect whether or not DNA is present in the droplet and will sort the empty droplets from the rest. From this point, the amplified DNA is released from the droplets and analyzed using capillary gel electrophoresis in order to read out the series of amplicons and thereby determine the identity of each virus. The following figure depicts the microfluidic process. For the abovementioned microfluidic process to work, a method for detecting amplification of target viral nucleic acids that does not interfere with the multiplexed biochemical reaction is required for downstream sorting and analysis. In this report, the successful development of a multiplexed PCR assay using SYBR Green I as a fluorescent dye to detect amplification of viral DNA that can later be integrated into microfluidic PCR system for sorting and analysis is shown.

  2. Nucleic acid sequences encoding D1 and D1/D2 domains of human coxsackievirus and adenovirus receptor (CAR)

    DOE Patents [OSTI]

    Freimuth, Paul I.

    2010-04-06

    The invention provides recombinant human CAR (coxsackievirus and adenovirus receptor) polypeptides which bind adenovirus. Specifically, polypeptides corresponding to adenovirus binding domain D1 and the entire extracellular domain of human CAR protein comprising D1 and D2 are provided. In another aspect, the invention provides nucleic acid sequences encoding these domains and expression vectors for producing the domains and bacterial cells containing such vectors. The invention also includes an isolated fusion protein comprised of the D1 polypeptide fused to a polypeptide which facilitates folding of D1 when expressed in bacteria. The functional D1 domain finds application in a therapeutic method for treating a patient infected with a CAR D1-binding virus, and also in a method for identifying an antiviral compound which interferes with viral attachment. The invention also provides a method for specifically targeting a cell for infection by a virus which binds to D1.

  3. Nanosize electropositive fibrous adsorbent

    DOE Patents [OSTI]

    Tepper, Frederick; Kaledin, Leonid

    2005-01-04

    Aluminum hydroxide fibers approximately 2 nanometers in diameter and with surface areas ranging from 200 to 650 m.sup.2 /g have been fount to be highly electropositive. When dispersed in water they are able to attach to and retain electronegative particles. When combined into a composite filter with other fibers or particles they can filter bacteria and nano size particulates such as viruses and colloidal particles at high flux through the filter. Such filters can be used for purification and sterilization of water, biological, medical and pharmaceutical fluids, and as a collector/concentrator for detection and assay of mirobes and viruses. The alumina fibers are also capable of filtering sub-micron inorganic and metallic particles to produce ultra pure water. The fibers are suitable as a substrate for growth of cells. Macromolicules such as proteins may be separated from each other based on their electronegative charges.

  4. Sub-micron filter

    DOE Patents [OSTI]

    Tepper, Frederick; Kaledin, Leonid

    2009-10-13

    Aluminum hydroxide fibers approximately 2 nanometers in diameter and with surface areas ranging from 200 to 650 m.sup.2/g have been found to be highly electropositive. When dispersed in water they are able to attach to and retain electronegative particles. When combined into a composite filter with other fibers or particles they can filter bacteria and nano size particulates such as viruses and colloidal particles at high flux through the filter. Such filters can be used for purification and sterilization of water, biological, medical and pharmaceutical fluids, and as a collector/concentrator for detection and assay of microbes and viruses. The alumina fibers are also capable of filtering sub-micron inorganic and metallic particles to produce ultra pure water. The fibers are suitable as a substrate for growth of cells. Macromolecules such as proteins may be separated from each other based on their electronegative charges.

  5. Predicting Individual Affect of Health Interventions to Reduce HPV Prevalence

    SciTech Connect (OSTI)

    Corley, Courtney D.; Mihalcea, Rada; Mikler, Armin R.; Sanfilippo, Antonio P.

    2011-04-01

    Recently, human papilloma virus has been implicated to cause several throat and oral cancers and hpv is established to cause most cervical cancers. A human papilloma virus vaccine has been proven successful to reduce infection incidence in FDA clinical trials and it is currently available in the United States. Current intervention policy targets adolescent females for vaccination; however, the expansion of suggested guidelines may extend to other age groups and males as well. This research takes a first step towards automatically predicting personal beliefs, regarding health intervention, on the spread of disease. Using linguistic or statistical approaches, sentiment analysis determines a texts affective content. Self-reported HPV vaccination beliefs published in web and social media are analyzed for affect polarity and leveraged as knowledge inputs to epidemic models. With this in mind, we have developed a discrete-time model to facilitate predicting impact on the reduction of HPV prevalence due to arbitrary age and gender targeted vaccination schemes.

  6. Software speeds detection of diseases and cancer-treatment targets

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Software speeds detection of diseases Software speeds detection of diseases and cancer-treatment targets The Lab has released an updated version of software that is now capable of identifying DNA from viruses and all parts of the Tree of Life. December 1, 2014 With Sequedex, a laptop computer can analyze DNA sequences faster than any current DNA sequencer can create them. With Sequedex, a laptop computer can analyze DNA sequences faster than any current DNA sequencer can create them. Contact

  7. Systems Biology in Prokaryote - Eukaryote Symbiosis | Stanford Synchrotron

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Radiation Lightsource Systems Biology in Prokaryote - Eukaryote Symbiosis Monday, June 25, 2012 - 12:00pm SLAC, SSRL Main Conference Room, 137-322 Allen M. Orville, Brookhaven National Laboratory Frontier challenges for macromolecular crystallography (MX) now include determining structures of trapped reactive intermediates, large macromolecules and viruses, membrane proteins, protein-protein complexes, and protein-nucleic acid complexes. Although structure and function are intimately linked,

  8. FNAL central email systems

    SciTech Connect (OSTI)

    Schmidt, Jack; Lilianstrom, Al; Pasetes, Ray; Hill, Kevin; /Fermilab

    2004-10-01

    The FNAL Email System is the primary point of entry for email destined for an employee or user at Fermilab. This centrally supported system is designed for reliability and availability. It uses multiple layers of protection to help ensure that: (1) SPAM messages are tagged properly; (2) All mail is inspected for viruses; and (3) Valid mail gets delivered. This system employs numerous redundant subsystems to accomplish these tasks.

  9. Science Summary

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    10 image Outside view of the T=4 subunit arrangement. » Links Scientific Highlight Johnson Lab » Share this Article Laboratree Ologeez SciLink LabSpaces Following the pH-dependent Conformational Changes of a Maturing Viral Capsid summary written by Raven Hanna The capsid that surrounds viruses is formed from subunit proteins that interact in specific ways to form a tight shell. The processes of coming together and forming interactions are multistep and complex and are fundamental events to

  10. 1

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Software speeds detection of diseases and cancer-treatment targets December 1, 2014 New technology puts bioinformatics within easy reach of health-care professionals, researchers and others LOS ALAMOS, N.M., Dec. 1, 2014-Los Alamos National Laboratory has released an updated version of powerful, award-winning bioinformatics software that is now capable of identifying DNA from viruses and all parts of the Tree of Life-putting diverse problems such as identifying pathogen-caused diseases,

  11. ALSNews Vol. 332

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    2 Print Hidden Rotational Symmetries in Magnetic Domain Patterns rotational symmetries While ubiquitous in nature, symmetry is not always evident. The first observation of hidden rotational symmetries in a magnetic system gives scientists a toolbox for discovering hidden symmetries in diverse material systems. Read more... Contact: Keoki Seu Borrowing from Nature to Produce Highly Structured Biomimetic Materials biomemetic materials Researchers have turned a benign virus into an engineering tool

  12. ALSNews Vol. 332

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    2 Print Hidden Rotational Symmetries in Magnetic Domain Patterns rotational symmetries While ubiquitous in nature, symmetry is not always evident. The first observation of hidden rotational symmetries in a magnetic system gives scientists a toolbox for discovering hidden symmetries in diverse material systems. Read more... Contact: Keoki Seu Borrowing from Nature to Produce Highly Structured Biomimetic Materials biomemetic materials Researchers have turned a benign virus into an engineering tool

  13. ALSNews Vol. 332

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    ALSNews Vol. 332 Print Hidden Rotational Symmetries in Magnetic Domain Patterns rotational symmetries While ubiquitous in nature, symmetry is not always evident. The first observation of hidden rotational symmetries in a magnetic system gives scientists a toolbox for discovering hidden symmetries in diverse material systems. Read more... Contact: Keoki Seu Borrowing from Nature to Produce Highly Structured Biomimetic Materials biomemetic materials Researchers have turned a benign virus into an

  14. Real Time Diagnostics for Algae-final-sm

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Real-time Monitoring And Diagnostics Detecting pathogens and predators to quickly recover from pond crashes Algal Pond Crash Detection Sandia National Laboratories is developing a suite of complementary technologies to help the emerging algae industry detect and quickly recover from algal pond crashes, an obstacle to large-scale algae cultivation for biofuels. Because of the way algae is grown and produced in most algal ponds, they are prone to attack by fungi, rotifers, viruses or other

  15. An Unusual Mechanism for the Antimicrobial Target Flavine-dependant

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Thymidylate Synthase (FTDS) An Unusual Mechanism for the Antimicrobial Target Flavine-dependant Thymidylate Synthase (FTDS) Classical thymidylate synthases, encoded by the thyA and TYMS genes, are present in most eukaryotes, including humans, and are frequently targeted by chemotherapeutic and antibiotic drugs. A recently discovered class of thymidylate synthases, the FDTSs encoded by the thyX gene has been found primarily in prokaryotes and viruses including several pathogens and biological

  16. High temperature flow-through device for rapid solubilization and analysis

    SciTech Connect (OSTI)

    West, Jason A. A.; Hukari, Kyle W.; Patel, Kamlesh D.; Peterson, Kenneth A.; Renzi, Ronald F.

    2009-09-22

    Devices and methods for thermally lysing of biological material, for example vegetative bacterial cells and bacterial spores, are provided. Hot solution methods for solubilizing bacterial spores are described. Systems for direct analysis are disclosed including thermal lysers coupled to sample preparation stations. Integrated systems capable of performing sample lysis, labeling and protein fingerprint analysis of biological material, for example, vegetative bacterial cells, bacterial spores and viruses are provided.

  17. Alamos National Laboratory theoretical biologists Bette Korber, Will Fischer, Sydeaka

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    strategy expands immune responses March 3, 2010 Mosaic vaccines show promise in reducing the spread of deadly virus LOS ALAMOS, New Mexico, March 3, 2010-Two teams of researchers-including Los Alamos National Laboratory theoretical biologists Bette Korber, Will Fischer, Sydeaka Watson, and James Szinger-have announced an HIV vaccination strategy that has been shown to expand the breadth and depth of immune responses in rhesus monkeys. Rhesus monkeys provide the best animal model currently

  18. High temperature flow-through device for rapid solubilization and analysis

    DOE Patents [OSTI]

    West, Jason A. A.; Hukari, Kyle W.; Patel, Kamlesh D.; Peterson, Kenneth A.; Renzi, Ronald F.

    2013-04-23

    Devices and methods for thermally lysing of biological material, for example vegetative bacterial cells and bacterial spores, are provided. Hot solution methods for solubilizing bacterial spores are described. Systems for direct analysis are disclosed including thermal lysers coupled to sample preparation stations. Integrated systems capable of performing sample lysis, labeling and protein fingerprint analysis of biological material, for example, vegetative bacterial cells, bacterial spores and viruses are provided.

  19. Patents -- Ivar Giaever (1977-1979)

    Office of Scientific and Technical Information (OSTI)

    7 - 1979) Giaever Page * Resources with Additional Information * Patents (1976, 1980-2008) US 4,011,308 METHOD FOR SURFACE IMMUNOLOGICAL DETECTION OF BIOLOGICAL PARTICLES BY THE USE OF TAGGED ANTIBODIES -- Giaever, Ivar; March 8, 1977 The detection of immunologically reactive biological particles such as viruses, bacteria and other cells is obtained by detection of the occurrence of an immunological reaction on a substrate between the particle to be detected and its tagged antibody. A first

  20. OSTI, US Dept of Energy, Office of Scientific and Technical Information |

    Office of Scientific and Technical Information (OSTI)

    Speeding access to science information from DOE and Beyond Microbes: Engines of Life by Kathy Chambers on Tue, Dec 1, 2015 Image credit: Lawrence Berkeley National Laboratory Image credit: Lawrence Berkeley National Laboratory Microbes - bacteria, fungi, protozoa, algae, and viruses - are the engines of life. Microbiomes or microbe communities account for 60% of living matter and are the most diverse life form on earth. The problem is that very little is understood about microbes and how

  1. New global HIV vaccine design shows promise in monkeys

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    New global HIV vaccine design shows promise in monkeys New global HIV vaccine design shows promise in monkeys These vaccines are specifically designed to present the most common forms of parts of the virus that can be recognized by the immune system. October 30, 2013 Bette Korber of Los Alamos National Laboratory, who developed a component of a new vaccine against HIV, now being tested in monkeys. Bette Korber of Los Alamos National Laboratory, who developed a component of a new vaccine against

  2. ORISE: Travelers' Health Campaign | How ORISE is Making a Difference

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Travelers' Health Campaign Travelers' Health Campaign takes critical messages worldwide Travelers' Health Campaign poster Click image to enlarge Traveling can be a dangerous transmitter of germs, bacteria and viruses such as H1N1. That makes airports, ship docks, train stations and bus depots among the most important places to spread the word about healthy practices and precautions. The Oak Ridge Institute for Science and Education (ORISE) has played a key role in preparing to get the

  3. Synthetic Biology: Engineering, Evolution and Design (SEED) Conference 2014

    SciTech Connect (OSTI)

    Voigt, Christopher

    2014-07-01

    SEED2014 focused on advances in the science and technology emerging from the field of synthetic biology. We broadly define this as technologies that accelerate the process of genetic engineering. It highlighted new tool development, as well as the application of these tools to diverse problems in biotechnology, including therapeutics, industrial chemicals and fuels, natural products, and agriculture. Systems spanned from in vitro experiments and viruses, through diverse bacteria, to eukaryotes (yeast, mammalian cells, plants).

  4. Probing Spatial, Electronic Structures with X-ray Scattering, Spectroscopic

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Techniques | Stanford Synchrotron Radiation Lightsource Probing Spatial, Electronic Structures with X-ray Scattering, Spectroscopic Techniques Wednesday, September 5, 2012 - 10:45am SLAC, Bldg. 137, Room 226 Gang Chen Seminar: Structures at atomic scales are traditionally determined through X-ray crystallography that amplifies scattering intensities by introducing spatial periodicity. For amorphous materials and many macromolecules, such as viruses, proteins and biofilms, it is hard to

  5. Foreign DNA Capture during CRISPR-CAS Adaptive Immunity

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Foreign DNA Capture during CRISPR-CAS Adaptive Immunity Foreign DNA Capture during CRISPR-CAS Adaptive Immunity Print Thursday, 21 January 2016 16:45 While we humans view bacteria as the enemy, bacteria have enemies too, for example, viruses. To protect themselves, bacteria have developed an adaptive-type immune system that revolves around a unit of DNA known as CRISPR, which stands for Clustered Regularly Interspaced Short Palindromic Repeats. A CRISPR unit of DNA is made up of

  6. Closer to HIV vaccine goal with new insight into viral factors

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Closer to HIV vaccine goal with new insight into viral factors New insight into viral factors that facilitate HIV transmission Understanding viral factors that facilitate transmission of HIV infection is critical to developing vaccines. February 14, 2012 Scientists work at the National Stable Isotope Resource LANL scientists found that the infected donor's predominant virus subpopulation in the genital tract differed from that in the blood. Comparing the HIV sequence population in each newly

  7. Lab partners with local company to market protein technology

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Protein technology Lab partners with local company to market protein technology Theranostech Inc. honed its skills in protein purification by developing an efficient test for Human Immunodeficiency Virus (HIV). July 14, 2008 Los Alamos National Laboratory sits on top of a once-remote mesa in northern New Mexico with the Jemez mountains as a backdrop to research and innovation covering multi-disciplines from bioscience, sustainable energy sources, to plasma physics and new materials. Los Alamos

  8. Crystal Structure of Cascade | Stanford Synchrotron Radiation Lightsource

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Crystal Structure of Cascade Friday, January 30, 2015 Immune pathways protect all organisms from infection by genetic invaders such as viruses. It was recently discovered that prokaryotes protect against invasion by bacteriophages via an RNA based adaptive immune system, called the CRISPR system (1, 2). By acting as a barrier to the exchange of genetic information, a major route for the acquisition of antibiotic-resistance and virulence factors, the CRISPR system modulates the evolution of

  9. Cybersecurity Expert Jim Mellander Retiring from NERSC

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Cybersecurity Expert Jim Mellander Retiring from NERSC Cybersecurity Expert Jim Mellander Retiring from NERSC From Detecting Sniffers to Protecting Credentials, He's Left His Mark in Cybersecurity October 22, 2014 Contact: Kathy Kincade, +1 510 495 2124, kkincade@lbl.gov mellander NERSC is losing one of its cybersecurity experts, but not to a bug or a virus. Jim Mellander, senior cybersecurity engineer at NERSC, is retiring November 1. He's been with NERSC since 2009 and affiliated with Berkeley

  10. DOE Science Showcase - Microbes | OSTI, US Dept of Energy, Office of

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Scientific and Technical Information Microbes Cells of the bacteria Shewanella putrefaciens CN32. Courtesy Department of Energy Microbes - bacteria, fungi, protozoa, algae, and viruses are mysterious engines of life. Microbiomes, or microbe communities, account for 60% of living matter and are the most diverse life form on earth yet little has been known about how they function. Recent advances in gene-sequencing technology have expanded our knowledge of microbiomes, and microbiomes research

  11. Layout 1

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    1 Yucca Mountain Pursuing a License MiniSAR offers promise Foams fight SARS virus What is Sandia's world-class science, technology, and engineering work define the Lab's value to the nation. These capabilities must remain on the cutting edge, because the security of the U.S. depends directly upon them. Sandia's Laboratory Directed Research and Development ( ) Program provides the flexibility to invest in long- term, high-risk, and potentally high-pay-off research and development that stretches

  12. How Dynein Binds to Microtubules

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    How Dynein Binds to Microtubules Print Cytoplasmic dynein is a protein complex responsible for the transport of a large variety of cargoes, from specific RNAs and proteins to whole organelles, in a directional fashion along microtubules that serve as cellular conveyor belts. Consistent with this central role, cytoplasmic dynein is associated with a number of disease-related processes, including the transport of viruses, neurodegeneration, and the mitotic checkpoint malfunctions that lead to

  13. How Dynein Binds to Microtubules

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    How Dynein Binds to Microtubules Print Cytoplasmic dynein is a protein complex responsible for the transport of a large variety of cargoes, from specific RNAs and proteins to whole organelles, in a directional fashion along microtubules that serve as cellular conveyor belts. Consistent with this central role, cytoplasmic dynein is associated with a number of disease-related processes, including the transport of viruses, neurodegeneration, and the mitotic checkpoint malfunctions that lead to

  14. How Dynein Binds to Microtubules

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    How Dynein Binds to Microtubules Print Cytoplasmic dynein is a protein complex responsible for the transport of a large variety of cargoes, from specific RNAs and proteins to whole organelles, in a directional fashion along microtubules that serve as cellular conveyor belts. Consistent with this central role, cytoplasmic dynein is associated with a number of disease-related processes, including the transport of viruses, neurodegeneration, and the mitotic checkpoint malfunctions that lead to

  15. How Dynein Binds to Microtubules

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    How Dynein Binds to Microtubules How Dynein Binds to Microtubules Print Wednesday, 29 April 2009 00:00 Cytoplasmic dynein is a protein complex responsible for the transport of a large variety of cargoes, from specific RNAs and proteins to whole organelles, in a directional fashion along microtubules that serve as cellular conveyor belts. Consistent with this central role, cytoplasmic dynein is associated with a number of disease-related processes, including the transport of viruses,

  16. Superhydrophobic surfaces (Patent) | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    Patent: Superhydrophobic surfaces Citation Details In-Document Search Title: Superhydrophobic surfaces Surfaces having a hierarchical structure--having features of both microscale and nanoscale dimensions--can exhibit superhydrophobic properties and advantageous condensation and heat transfer properties. The hierarchical surfaces can be fabricated using biological nanostructures, such as viruses as a self-assembled nanoscale template. Authors: Wang, Evelyn N ; McCarthy, Matthew ; Enright, Ryan ;

  17. The Energy

    Energy Savers [EERE]

    NATIONAL AND HOMELAND SECURITY Continued next page Network Interconnectivity The business world is online. So are hackers. The dangers and complica- tions of controlling corporate network access and informa- tion flow from unauthorized users has been a consistent problem since the Inter- net's inception. The guiding principal seems to be that if a programmer can build it, a hacker can destroy it. A virtual back and forth battle of patches and worms, upgrades and viruses has evolved. In addition,

  18. 03-08-2010 NNSA-B-10-0097

    National Nuclear Security Administration (NNSA)

    8-2010 NNSA-B-10-0097 Sandia National Laboratories/New Mexico (SNL/NM) proposes to perform neutron reflectivity and fluorescence microscopy studies of the structure and activity of the negative factor (Nef) protein from Human Immunodeficiency Virus (HIV) bound to lipid membranes. Some of the proposed work with the recombinant proteins - the neutron reflection (NR) - would be performed at national neutron-scattering user facilities across the country; initial work would be performed at the

  19. Audit Report: IG-0500 | Department of Energy

    Energy Savers [EERE]

    00 Audit Report: IG-0500 April 5, 2001 Virus Protection Strategies and Cyber Security Incident Reporting Information Technology (IT) plays an integral role in the programs and operations of the Department of Energy. In Fiscal Year 2001, the Department budgeted $1.4 billion for the acquisition and maintenance of IT related resources, a portion of which supports the Advanced Strategic Computing Initiative. These resources, and the programs they support, are vulnerable to malicious software,

  20. Transformation of gram positive bacteria by sonoporation

    DOE Patents [OSTI]

    Yang, Yunfeng; Li, Yongchao

    2014-03-11

    The present invention provides a sonoporation-based method that can be universally applied for delivery of compounds into Gram positive bacteria. Gram positive bacteria which can be transformed by sonoporation include, for example, Bacillus, Streptococcus, Acetobacterium, and Clostridium. Compounds which can be delivered into Gram positive bacteria via sonoporation include nucleic acids (DNA or RNA), proteins, lipids, carbohydrates, viruses, small organic and inorganic molecules, and nano-particles.

  1. What is Malware

    Broader source: Energy.gov (indexed) [DOE]

    What is Malware? Computer users of all ages have heard different terms such as virus, worm, or Trojan that describe malicious code or programs that can infect computers and mobile devices. In today's world, these different terms are now called malware. Simply put, malware is a computer program used to perform malicious actions. In fact, the term malware is a combination of the words malicious and software. Cyber criminals can use malware to infect a computing device, and then take control of the

  2. Multiplexed Molecular Assays for Rapid Rule-Out of Foot-and-Mouth Disease

    SciTech Connect (OSTI)

    Lenhoff, R; Naraghi-Arani, P; Thissen, J; Olivas, J; Carillo, C; Chinn, C; Rasmussen, M; Messenger, S; Suer, L; Smith, S M; Tammero, L; Vitalis, E; Slezak, T R; Hullinger, P J; Hindson, B J; Hietala, S; Crossley, B; Mcbride, M

    2007-06-26

    A nucleic acid-based multiplexed assay was developed that combines detection of foot-and-mouth disease virus (FMDV) with rule-out assays for two other foreign animal diseases and four domestic animal diseases that cause vesicular or ulcerative lesions indistinguishable from FMDV infection in cattle, sheep and swine. The FMDV 'look-alike' diagnostic assay panel contains five PCR and twelve reverse transcriptase PCR (RT-PCR) signatures for a total of seventeen simultaneous PCR amplifications for seven diseases plus incorporating four internal assay controls. It was developed and optimized to amplify both DNA and RNA viruses simultaneously in a single tube and employs Luminex{trademark} liquid array technology. Assay development including selection of appropriate controls, a comparison of signature performance in single and multiplex testing against target nucleic acids, as well of limits of detection for each of the individual signatures is presented. While this assay is a prototype and by no means a comprehensive test for FMDV 'look-alike' viruses, an assay of this type is envisioned to have benefit to a laboratory network in routine surveillance and possibly for post-outbreak proof of freedom from foot-and-mouth disease.

  3. A comprehensive collection of systems biology data characterizing the host response to viral infection

    SciTech Connect (OSTI)

    Aevermann, Brian D.; Pickett, Brett E.; Kumar, Sanjeev; Klem, Edward B.; Agnihothram, Sudhakar; Askovich, Peter S.; Bankhead, Armand; Bolles, Meagan; Carter, Victoria; Chang, Jean H.; Clauss, Therese R. W.; Dash, Pradyot; Diercks, Alan H.; Eisfeld, Amie J.; Ellis, Amy L.; Fan, Shufang; Ferris, Martin T.; Gralinski, Lisa; Green, Richard; Gritsenko, Marina A.; Hatta, Masato; Heegel, Robert A.; Jacobs, Jon M.; Jeng, Sophia; Josset, Laurence; Kaiser, Shari M.; Kelly, Sarah; Law, Gale Lynn; Li, Chengjun; Li, Jiangning; Long, Casey; Luna, Maria L.; Matzke, Melissa M.; McDermott, Jason E.; Menachery, Vineet; Metz, Thomas O.; Mitchell, Hugh D.; Monroe, Matthew E.; Navarro, Garnet; Neumann, Gabriele; Podyminogin, Rebecca L.; Purvine, Samuel O.; Rosenberger, Carrie; Sanders, Catherine J.; Schepmoes, Athena A.; Shukla, Anil K.; Sims, Amy; Sova, Pavel; Tam, Vincent C.; Tchitchek, Nicholas; Thomas, Paul G.; Tilton, Susan C.; Totura, Allison L.; Wang, Jing; Webb-Robertson, Bobbie-Jo M.; Wen, Ji; Weiss, Jeffrey M.; Yang, Feng; Yount, Boyd; Zhang, Qibin; Mcweeney, Shannon K.; Smith, Richard D.; Waters, Katrina M.; Kawaoka, Yoshihiro; Baric, Ralph; Aderem, Alan; Katze, Michael G.; Scheuermann, Richard H.

    2014-10-14

    The Systems Biology for Infectious Diseases Research program was established by the U.S. National Institute of Allergy and Infectious Diseases to investigate host-pathogen interactions at a systems level. This program generated 47 transcriptomic and proteomic datasets from 30 studies that investigate in vivo and in vitro host responses to viral infections. Human pathogens in the Orthomyxoviridae and Coronaviridae families, especially pandemic H1N1 and avian H5N1 influenza A viruses and severe acute respiratory syndrome coronavirus (SARS-CoV), were investigated. Study validation was demonstrated via experimental quality control measures and meta-analysis of independent experiments performed under similar conditions. Primary assay results are archived at the GEO and PeptideAtlas public repositories, while processed statistical results together with standardized metadata are publically available at the Influenza Research Database (www.fludb.org) and the Virus Pathogen Resource (www.viprbrc.org). As a result, by comparing data from mutant versus wild-type virus and host strains, RNA versus protein differential expression, and infection with genetically similar strains, these data can be used to further investigate genetic and physiological determinants of host responses to viral infection.

  4. Mos1 transposon-based transformation of fish cell lines using baculoviral vectors

    SciTech Connect (OSTI)

    Yokoo, Masako; Fujita, Ryosuke; Innate Immunity Laboratory, Graduate School of Life Science and Creative Research Institution, Hokkaido University, Sapporo 001-0021 ; Nakajima, Yumiko; Yoshimizu, Mamoru; Kasai, Hisae; Asano, Shin-ichiro; Bando, Hisanori

    2013-09-13

    Highlights: ‱The baculovirus vector infiltrates the cells of economic important fishes. ‱Drosophila Mos1 transposase expressed in fish cells maintains its ability to localize to the nucleus. ‱The baculoviral vector carrying Mos1 is a useful tool to stably transform fish cells. -- Abstract: Drosophila Mos1 belongs to the mariner family of transposons, which are one of the most ubiquitous transposons among eukaryotes. We first determined nuclear transportation of the Drosophila Mos1-EGFP fusion protein in fish cell lines because it is required for a function of transposons. We next constructed recombinant baculoviral vectors harboring the Drosophila Mos1 transposon or marker genes located between Mos1 inverted repeats. The infectivity of the recombinant virus to fish cells was assessed by monitoring the expression of a fluorescent protein encoded in the viral genome. We detected transgene expression in CHSE-214, HINAE, and EPC cells, but not in GF or RTG-2 cells. In the co-infection assay of the Mos1-expressing virus and reporter gene-expressing virus, we successfully transformed CHSE-214 and HINAE cells. These results suggest that the combination of a baculovirus and Mos1 transposable element may be a tool for transgenesis in fish cells.

  5. The Crystal Structure of the RNA-Dependent RNA Polymerase from Human Rhinovirus: A Dual Function Target for Common Cold Antiviral Therapy

    SciTech Connect (OSTI)

    Love, Robert A.; Maegley, Karen A.; Yu, Xiu; Ferre, RoseAnn; Lingardo, Laura K.; Diehl, Wade; Parge, Hans E.; Dragovich, Peter S.; Fuhrman, Shella A.

    2010-11-16

    Human rhinoviruses (HRV), the predominant members of the Picornaviridae family of positive-strand RNA viruses, are the major causative agents of the common cold. Given the lack of effective treatments for rhinoviral infections, virally encoded proteins have become attractive therapeutic targets. The HRV genome encodes an RNA-dependent RNA polymerase (RdRp) denoted 3D{sup pol}, which is responsible for replicating the viral genome and for synthesizing a protein primer used in the replication. Here the crystal structures for three viral serotypes (1B, 14, and 16) of HRV 3D{sup pol} have been determined. The three structures are very similar to one another, and to the closely related poliovirus (PV) 3D{sup pol} enzyme. Because the reported PV crystal structure shows significant disorder, HRV 3D{sup pol} provides the first complete view of a picornaviral RdRp. The folding topology of HRV 3D{sup pol} also resembles that of RdRps from hepatitis C virus (HCV) and rabbit hemorrhagic disease virus (RHDV) despite very low sequence homology.

  6. A comprehensive collection of systems biology data characterizing the host response to viral infection

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Aevermann, Brian D.; Pickett, Brett E.; Kumar, Sanjeev; Klem, Edward B.; Agnihothram, Sudhakar; Askovich, Peter S.; Bankhead, Armand; Bolles, Meagan; Carter, Victoria; Chang, Jean H.; et al

    2014-10-14

    The Systems Biology for Infectious Diseases Research program was established by the U.S. National Institute of Allergy and Infectious Diseases to investigate host-pathogen interactions at a systems level. This program generated 47 transcriptomic and proteomic datasets from 30 studies that investigate in vivo and in vitro host responses to viral infections. Human pathogens in the Orthomyxoviridae and Coronaviridae families, especially pandemic H1N1 and avian H5N1 influenza A viruses and severe acute respiratory syndrome coronavirus (SARS-CoV), were investigated. Study validation was demonstrated via experimental quality control measures and meta-analysis of independent experiments performed under similar conditions. Primary assay results are archivedmore » at the GEO and PeptideAtlas public repositories, while processed statistical results together with standardized metadata are publically available at the Influenza Research Database (www.fludb.org) and the Virus Pathogen Resource (www.viprbrc.org). As a result, by comparing data from mutant versus wild-type virus and host strains, RNA versus protein differential expression, and infection with genetically similar strains, these data can be used to further investigate genetic and physiological determinants of host responses to viral infection.« less

  7. Quantitative multiplex detection of biomarkers on a waveguide-based biosensor using quantum dots

    SciTech Connect (OSTI)

    Xie, Hongzhi; Mukundan, Harshini; Martinez, Jennifer S; Swanson, Basil I; Anderson, Aaron S; Grace, Kevin

    2009-01-01

    The quantitative, simultaneous detection of multiple biomarkers with high sensitivity and specificity is critical for biomedical diagnostics, drug discovery and biomarker characterization [Wilson 2006, Tok 2006, Straub 2005, Joos 2002, Jani 2000]. Detection systems relying on optical signal transduction are, in general, advantageous because they are fast, portable, inexpensive, sensitive, and have the potential for multiplex detection of analytes of interest. However, conventional immunoassays for the detection of biomarkers, such as the Enzyme Linked Immunosorbant Assays (ELISAs) are semi-quantitative, time consuming and insensitive. ELISA assays are also limited by high non-specific binding, especially when used with complex biological samples such as serum and urine (REF). Organic fluorophores that are commonly used in such applications lack photostability and possess a narrow Stoke's shift that makes simultaneous detection of multiple fluorophores with a single excitation source difficult, thereby restricting their use in multiplex assays. The above limitations with traditional assay platforms have resulted in the increased use of nanotechnology-based tools and techniques in the fields of medical imaging [ref], targeted drug delivery [Caruthers 2007, Liu 2007], and sensing [ref]. One such area of increasing interest is the use of semiconductor quantum dots (QDs) for biomedical research and diagnostics [Gao and Cui 2004, Voura 2004, Michalet 2005, Chan 2002, Jaiswal 2004, Gao 2005, Medintz 2005, So 2006 2006, Wu 2003]. Compared to organic dyes, QDs provide several advantages for use in immunoassay platforms, including broad absorption bands with high extinction coefficients, narrow and symmetric emission bands with high quantum yields, high photostablility, and a large Stokes shift [Michalet 2005, Gu 2002]. These features prompted the use of QDs as probes in biodetection [Michalet 2005, Medintz 2005]. For example, Jaiswal et al. reported long term multiple color imaging of live cells using QD-bioconjugates [Jaiswal 2003]. Gao [Gao 2004] and So [So 2006] have used QDs as probes for in-vivo cancer targeting and imaging. Medintz et al. reported self-assembled QD-based biosensors for detection of analytes based on energy transfer [Medintz 2003]. Others have developed an approach for multiplex optical encoding of biomolecules using QDs [Han 2001]. Immunoassays have also benefited from the advantages of QDs. Recently, dihydrolipoic acid (DHLA) capped-QDs have been attached to antibodies and used as fluorescence reporters in plate-based multiplex immunoassays [Goodman 2004]. However, DHLA-QDs are associated with low quantum efficiency and are unstable at neutral pH. These problems limit the application of this technology to the sensitive detection of biomolecules, especially in complex biological samples. Thus, the development of a rapid, sensitive, quantitative, and specific multiplex platform for the detection of biomarkers in difficult samples remains an elusive target. The goal stated above has applications in many fields including medical diagnostics, biological research, and threat reduction. The current decade alone has seen the development of a need to rapidly and accurately detect potential biological warfare agents. For example, current methods for the detection of anthrax are grossly inadequate for a variety of reasons including long incubation time (5 days from time of exposure to onset of symptoms) and non-specific ('flu-like') symptoms. When five employees of the United State Senate were exposed to B. anthracis in the mail (2001), only one patient had a confirmed diagnosis before death. Since then, sandwich immunoassays using both colorimetric and fluorescence detectors have been developed for key components of the anthrax lethal toxin, namely protective antigen (PA), lethal factor (LF), and the edema factor [Mourez 2001]. While these platforms were successful in assays against anthrax toxins, the sensitivity was poor. Furthermore, no single platform exists for the simultaneous and quantitative detection of mul

  8. Genetic disruption of KSHV major latent nuclear antigen LANA enhances viral lytic transcriptional program

    SciTech Connect (OSTI)

    Li Qiuhua; Zhou Fuchun; Ye Fengchun; Gao Shoujiang

    2008-09-30

    Following primary infection, KSHV establishes a lifelong persistent latent infection in the host. The mechanism of KSHV latency is not fully understood. The latent nuclear antigen (LANA or LNA) encoded by ORF73 is one of a few viral genes expressed during KSHV latency, and is consistently detected in all KSHV-related malignancies. LANA is essential for KSHV episome persistence, and regulates the expression of viral lytic genes through epigenetic silencing, and inhibition of the expression and transactivation function of the key KSHV lytic replication initiator RTA (ORF50). In this study, we used a genetic approach to examine the role of LANA in regulating KSHV lytic replication program. Deletion of LANA did not affect the expression of its adjacent genes vCyclin (ORF72) and vFLIP (ORF71). In contrast, the expression levels of viral lytic genes including immediate-early gene RTA, early genes MTA (ORF57), vIL-6 (ORF-K2) and ORF59, and late gene ORF-K8.1 were increased before and after viral lytic induction with 12-O-tetradecanoyl-phorbol-13-acetate and sodium butyrate. This enhanced expression of viral lytic genes was also observed following overexpression of RTA with or without simultaneous chemical induction. Consistent with these results, the LANA mutant cells produced more infectious virions than the wild-type virus cells did. Furthermore, genetic repair of the mutant virus reverted the phenotypes to those of wild-type virus. Together, these results have demonstrated that, in the context of viral genome, LANA contributes to KSHV latency by regulating the expression of RTA and its downstream genes.

  9. FY09 Final Report for LDRD Project: Understanding Viral Quasispecies Evolution through Computation and Experiment

    SciTech Connect (OSTI)

    Zhou, C

    2009-11-12

    In FY09 they will (1) complete the implementation, verification, calibration, and sensitivity and scalability analysis of the in-cell virus replication model; (2) complete the design of the cell culture (cell-to-cell infection) model; (3) continue the research, design, and development of their bioinformatics tools: the Web-based structure-alignment-based sequence variability tool and the functional annotation of the genome database; (4) collaborate with the University of California at San Francisco on areas of common interest; and (5) submit journal articles that describe the in-cell model with simulations and the bioinformatics approaches to evaluation of genome variability and fitness.

  10. Human Retroviruses and AIDS. A compilation and analysis of nucleic acid and amino acid sequences: I--II; III--V

    SciTech Connect (OSTI)

    Myers, G.; Korber, B.; Wain-Hobson, S.; Smith, R.F.; Pavlakis, G.N.

    1993-12-31

    This compendium and the accompanying floppy diskettes are the result of an effort to compile and rapidly publish all relevant molecular data concerning the human immunodeficiency viruses (HIV) and related retroviruses. The scope of the compendium and database is best summarized by the five parts that it comprises: (I) HIV and SIV Nucleotide Sequences; (II) Amino Acid Sequences; (III) Analyses; (IV) Related Sequences; and (V) Database Communications. Information within all the parts is updated at least twice in each year, which accounts for the modes of binding and pagination in the compendium.

  11. Multiplex detection of respiratory pathogens

    DOE Patents [OSTI]

    McBride, Mary (Brentwood, CA); Slezak, Thomas (Livermore, CA); Birch, James M. (Albany, CA)

    2012-07-31

    Described are kits and methods useful for detection of respiratory pathogens (influenza A (including subtyping capability for H1, H3, H5 and H7 subtypes) influenza B, parainfluenza (type 2), respiratory syncytial virus, and adenovirus) in a sample. Genomic sequence information from the respiratory pathogens was analyzed to identify signature sequences, e.g., polynucleotide sequences useful for confirming the presence or absence of a pathogen in a sample. Primer and probe sets were designed and optimized for use in a PCR based, multiplexed Luminex assay to successfully identify the presence or absence of pathogens in a sample.

  12. Influenza sensor

    DOE Patents [OSTI]

    Swanson, Basil I. (Los Alamos, NM); Song, Xuedong (Los Alamos, NM); Unkefer, Clifford (Los Alamos, NM); Silks, III, Louis A. (Los Alamos, NM); Schmidt, Jurgen G. (Los Alamos, NM)

    2003-09-30

    A sensor for the detection of tetrameric multivalent neuraminidase within a sample is disclosed, where a positive detection indicates the presence of a target virus within the sample. Also disclosed is a trifunctional composition of matter including a trifunctional linker moiety with groups bonded thereto including (a) an alkyl chain adapted for attachment to a substrate, (b) a fluorescent moiety capable of generating a fluorescent signal, and (c) a recognition moiety having a spacer group of a defined length thereon, the recognition moiety capable of binding with tetrameric multivalent neuraminidase.

  13. Influenza Sensor

    DOE Patents [OSTI]

    Swanson, Basil I. (Los Alamos, NM); Song, Xuedong (Los Alamos, NM); Unkefer, Clifford (Los Alamos, NM); Silks, III, Louis A. (Los Alamos, NM); Schmidt, Jurgen G. (Los Alamos, NM)

    2006-03-28

    A sensor for the detection of tetrameric multivalent neuraminidase within a sample is disclosed, where a positive detection indicates the presence of a target virus within the sample. Also disclosed is a trifunctional composition of matter including a trifunctional linker moiety with groups bonded thereto including (a) an alkyl chain adapted for attachment to a substrate, (b) a fluorescent moiety capable of generating a fluorescent signal, and (c) a recognition moiety having a spacer group of a defined length thereon, the recognition moiety capable of binding with tetrameric multivalent neuraminidase.

  14. Influenza Sensor

    DOE Patents [OSTI]

    Swanson, Basil I. (Los Alamos, NM); Song, Xuedong (Los Alamos, NM); Unkefer, Clifford (Los Alamos, NM); Silks, III, Louis A. (Los Alamos, NM); Schmidt, Jurgen G. (Los Alamos, NM)

    2005-05-17

    A sensor for the detection of tetrameric multivalent neuraminidase within a sample is disclosed, where a positive detection indicates the presence of a target virus within the sample. Also disclosed is a trifunctional composition of matter including a trifunctional linker moiety with groups bonded thereto including (a) an alkyl chain adapted for attachment to a substrate, (b) a fluorescent moiety capable of generating a fluorescent signal, and (c) a recognition moiety having a spacer group of a defined length thereon, the recognition moiety capable of binding with tetrameric multivalent neuraminidase.

  15. Modular Automated Processing System (MAPS) for analysis of biological samples.

    SciTech Connect (OSTI)

    Gil, Geun-Cheol; Chirica, Gabriela S.; Fruetel, Julia A.; VanderNoot, Victoria A.; Branda, Steven S.; Schoeniger, Joseph S.; Throckmorton, Daniel J.; Brennan, James S.; Renzi, Ronald F.

    2010-10-01

    We have developed a novel modular automated processing system (MAPS) that enables reliable, high-throughput analysis as well as sample-customized processing. This system is comprised of a set of independent modules that carry out individual sample processing functions: cell lysis, protein concentration (based on hydrophobic, ion-exchange and affinity interactions), interferent depletion, buffer exchange, and enzymatic digestion of proteins of interest. Taking advantage of its unique capacity for enclosed processing of intact bioparticulates (viruses, spores) and complex serum samples, we have used MAPS for analysis of BSL1 and BSL2 samples to identify specific protein markers through integration with the portable microChemLab{trademark} and MALDI.

  16. Investigation of type-I interferon dysregulation by arenaviruses : a multidisciplinary approach.

    SciTech Connect (OSTI)

    Kozina, Carol L.; Moorman, Matthew Wallace; Branda, Catherine; Wu, Meiye; Manginell, Ronald Paul; Ricken, James Bryce; James, Conrad D.; Negrete, Oscar A.; Misra, Milind; Carson, Bryan D.

    2011-09-01

    This report provides a detailed overview of the work performed for project number 130781, 'A Systems Biology Approach to Understanding Viral Hemorrhagic Fever Pathogenesis.' We report progress in five key areas: single cell isolation devices and control systems, fluorescent cytokine and transcription factor reporters, on-chip viral infection assays, molecular virology analysis of Arenavirus nucleoprotein structure-function, and development of computational tools to predict virus-host protein interactions. Although a great deal of work remains from that begun here, we have developed several novel single cell analysis tools and knowledge of Arenavirus biology that will facilitate and inform future publications and funding proposals.

  17. The future of electron microscopy

    SciTech Connect (OSTI)

    Zhu, Yimei; Durr, Hermann

    2015-04-01

    Seeing is believing. So goes the old adage and seen evidence is undoubtedly satisfying because it can be interpreted easily, though not always correctly. For centuries, humans have developed such instruments as telescopes that observe the heavens and microscopes that reveal bacteria and viruses. The 2014 Nobel Prize in Chemistry was awarded to Eric Betzig, Stefan Hell, and William Moerner for their foundational work on superresolution fluorescence microscopy in which they overcame the Abbe diffraction limit for the resolving power of conventional light microscopes. (See Physics Today, December 2014, page 18.) That breakthrough enabled discoveries in biological research and testifies to the importance of modern microscopy.

  18. Protein folding and non-conventional drug design: a primer for nuclear structure physicists

    SciTech Connect (OSTI)

    Broglia, R.A. [Dipartimento di Fisica, Universita di Milano, Via Celoria 16, I-20133 Milan (Italy); INFN, Sezione di Milano, Via Celoria 16, I-20133 Milan (Italy); Niels Bohr Institute, University of Copenhagen, 2100 Copenhagen (Denmark); Tiana, G.; Provasi, D. [Dipartimento di Fisica, Universita di Milano, Via Celoria 16, I-20133 Milan (Italy); INFN, Sezione di Milano, Via Celoria 16, I-20133 Milan (Italy)

    2004-02-27

    Some of the paradigms emerging from the study of the phenomena of phase transitions in finite many-body systems, like e.g. the atomic nucleus can be used at profit to solve the protein folding problem within the framework of simple (although not oversimplified) models. From this solution a paradigm emerges for the design of non-conventional drugs, which inhibit enzymatic action without inducing resistance (mutations). The application of these concepts to the design of an inhibitor to the HIV-protease central in the life cycle of the HIV virus is discussed.

  19. The future of electron microscopy

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Zhu, Yimei; Durr, Hermann

    2015-04-01

    Seeing is believing. So goes the old adage and seen evidence is undoubtedly satisfying because it can be interpreted easily, though not always correctly. For centuries, humans have developed such instruments as telescopes that observe the heavens and microscopes that reveal bacteria and viruses. The 2014 Nobel Prize in Chemistry was awarded to Eric Betzig, Stefan Hell, and William Moerner for their foundational work on superresolution fluorescence microscopy in which they overcame the Abbe diffraction limit for the resolving power of conventional light microscopes. (See Physics Today, December 2014, page 18.) That breakthrough enabled discoveries in biological research and testifiesmore » to the importance of modern microscopy.« less

  20. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    Switch to Detail View for this search SciTech Connect Search Results Page 1 of 2 Search for: All records Creators/Authors contains: "Gellman, Samuel H" × Sort by Relevance Sort by Date (newest first) Sort by Date (oldest first) Sort by Relevance « Prev Select page number Go to page: 1 of 2 1 » Next » Everything17 Electronic Full Text0 Citations17 Multimedia0 Datasets0 Software0 Filter Results Filter by Subject proteins (4) basic biological sciences (3) aids virus (2) applied life

  1. AFV CoverSheet

    Office of Scientific and Technical Information (OSTI)

    1253 (Accepted Manuscript) Recombination Enhances HIV-1 Envelope Diversity by Facilitating the Survival of Latent Genomic Fragments in the Plasma Virus Population Immonen, Taina Tuulia Conway, Jessica M Romero-Severson, Ethan Perelson, Alan S. Leitner, Thomas Kenneth Provided by the author(s) and the Los Alamos National Laboratory (2016-01-13). To be published in: PLoS Computational Biology; Vol.11, iss.12, p.e1004625, Dec, 2015 DOI to publisher's version: 10.1371/journal. pcbi.1004625 Permalink

  2. Crystal Structure of the Hexameric Assembly Unit of the HIV Capsid

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Crystal Structure of the Hexameric Assembly Unit of the HIV Capsid The ribonucleoprotein genomic complex of human immunodeficiency virus type 1 (HIV-1) is encased within the mature capsid, a predominantly cone-shaped shell assembled from ~1,500 copies of the viral CA protein [1]. Packaging of the viral genome and its associated enzymes into the capsid is required for their delivery into host cells. To form a closed shell the CA protein assembles into ~250 hexamers. The CA hexamer consists of a

  3. Link Alpha M

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    m A B C D E F G H I J K L M N O P Q R S T V W Y Z Filter by alpha... A B C D E F G H I J K L M N O P Q R S T U V W Y Z Macintosh User Group (LBNL-MUG) Mail Services (Facilities Dep't.) Malware/Virus Protection and Prevention Mammary: Human Mammary Epithelial Cell (HMEC) Map: Berkeley Lab Global Talent Map Map: Lab Shuttle Bus Map Maps: Berkeley Lab Interactive Site Map Maps: Berkeley Lab Printable Site Map Massage Material Safety Data Sheets: MSDSs Material Transfer Agreements Materials Sciences

  4. Membranes Key to Biorefinery Success | GE Global Research

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Miming living organisms processes for biorefineries Click to email this to a friend (Opens in new window) Share on Facebook (Opens in new window) Click to share (Opens in new window) Click to share on LinkedIn (Opens in new window) Click to share on Tumblr (Opens in new window) Miming living organisms processes for biorefineries Jimmy Lopez 2015.09.10 Membranes play a key role in the human body, filtering out bacteria and viruses and also ensuring cells absorb essential nutrients. They are

  5. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    Switch to Detail View for this search SciTech Connect Search Results Page 1 of 1 Search for: All records Creators/Authors contains: "Wu, jianguo" × Sort by Relevance Sort by Date (newest first) Sort by Date (oldest first) Sort by Relevance « Prev Next » Everything6 Electronic Full Text1 Citations5 Multimedia0 Datasets0 Software0 Filter Results Filter by Subject applied life sciences (4) gene regulation (3) viruses (3) cell proliferation (2) human populations (2) nitric oxide (2)

  6. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    Switch to Detail View for this search SciTech Connect Search Results Page 1 of 5 Search for: All records Creators/Authors contains: "Yuan, Fang" × Sort by Relevance Sort by Date (newest first) Sort by Date (oldest first) Sort by Relevance « Prev Select page number Go to page: 1 of 5 1 » Next » Everything41 Electronic Full Text0 Citations41 Multimedia0 Datasets0 Software0 Filter Results Filter by Subject crystal structure (11) aids virus (7) design (7) synthesis (7) enzymes (6)

  7. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    Switch to Detail View for this search SciTech Connect Search Results Page 2 of 2 Search for: All records Creators/Authors contains: "Gellman, Samuel H" × Sort by Relevance Sort by Date (newest first) Sort by Date (oldest first) Sort by Relevance « Prev Select page number Go to page: 2 of 2 2 » Next » Everything17 Electronic Full Text0 Citations17 Multimedia0 Datasets0 Software0 Filter Results Filter by Subject proteins (4) basic biological sciences (3) aids virus (2) applied life

  8. An Insertion Mutation That Distorts Antibody Binding Site Architecture Enhances Function of a Human Antibody

    SciTech Connect (OSTI)

    Krause, Jens C.; Ekiert, Damian C.; Tumpey, Terrence M.; Smith, Patricia B.; Wilson, Ian A.; Crowe, Jr., James E.

    2011-09-02

    The structural and functional significance of somatic insertions and deletions in antibody chains is unclear. Here, we demonstrate that a naturally occurring three-amino-acid insertion within the influenza virus-specific human monoclonal antibody 2D1 heavy-chain variable region reconfigures the antibody-combining site and contributes to its high potency against the 1918 and 2009 pandemic H1N1 influenza viruses. The insertion arose through a series of events, including a somatic point mutation in a predicted hot-spot motif, introduction of a new hot-spot motif, a molecular duplication due to polymerase slippage, a deletion due to misalignment, and additional somatic point mutations. Atomic resolution structures of the wild-type antibody and a variant in which the insertion was removed revealed that the three-amino-acid insertion near the base of heavy-chain complementarity-determining region (CDR) H2 resulted in a bulge in that loop. This enlarged CDR H2 loop impinges on adjacent regions, causing distortion of the CDR H1 architecture and its displacement away from the antigen-combining site. Removal of the insertion restores the canonical structure of CDR H1 and CDR H2, but binding, neutralization activity, and in vivo activity were reduced markedly because of steric conflict of CDR H1 with the hemagglutinin antigen.

  9. Final Report for DOE grant no. DE-FG02-04ER63883: Can soil genomics predict the impact of precipitation on nitrous oxide flux from soil

    SciTech Connect (OSTI)

    Egbert Schwartz

    2008-12-15

    Nitrous oxide is a potent greenhouse gas that is released by microorganisms in soil. However, the production of nitrous oxide in soil is highly variable and difficult to predict. Future climate change may have large impacts on nitrous oxide release through alteration of precipitation patterns. We analyzed DNA extracted from soil in order to uncover relationships between microbial processes, abundance of particular DNA sequences and net nitrous oxide fluxes from soil. Denitrification, a microbial process in which nitrate is used as an electron acceptor, correlated with nitrous oxide flux from soil. The abundance of ammonia oxidizing archaea correlated positively, but weakly, with nitrous oxide production in soil. The abundance of bacterial genes in soil was negatively correlated with gross nitrogen mineralization rates and nitrous oxide release from soil. We suggest that the most important control over nitrous oxide production in soil is the growth and death of microorganisms. When organisms are growing nitrogen is incorporated into their biomass and nitrous oxide flux is low. In contrast, when microorganisms die, due to predation or infection by viruses, inorganic nitrogen is released into the soil resulting in nitrous oxide release. Higher rates of precipitation increase access to microorganisms by predators or viruses through filling large soil pores with water and therefore can lead to large releases of nitrous oxide from soil. We developed a new technique, stable isotope probing with 18O-water, to study growth and mortality of microorganisms in soil.

  10. Ecological succession and viability of human-associated microbiota on restroom surfaces

    SciTech Connect (OSTI)

    Gibbons, Sean M.; Schwartz, Tara; Fouquier, Jennifer; Mitchell, Michelle; Sangwan, Naseer; Gilbert, Jack A.; Kelley, Scott T.; Elkins, C. A.

    2014-11-14

    Human-associated bacteria dominate the built environment (BE). Following decontamination of floors, toilet seats, and soap dispensers in four public restrooms, in situ bacterial communities were characterized hourly, daily, and weekly to determine their successional ecology. The viability of cultivable bacteria, following the removal of dispersal agents (humans), was also assessed hourly. A late-successional community developed within 5 to 8 h on restroom floors and showed remarkable stability over weeks to months. Despite late-successional dominance by skin- and outdoor-associated bacteria, the most ubiquitous organisms were predominantly gut-associated taxa, which persisted following exclusion of humans. Staphylococcus represented the majority of the cultivable community, even after several hours of human exclusion. Methicillin-resistant Staphylococcus aureus (MRSA)-associated virulence genes were found on floors but were not present in assembled Staphylococcus pan-genomes. Viral abundances, which were predominantly enterophages, human papilloma virus, and herpesviruses, were significantly correlated with bacterial abundances and showed an unexpectedly low virus-to-bacterium ratio in surface-associated samples, suggesting that bacterial hosts are mostly dormant on BE surfaces.

  11. Competitive exclusion by autologous antibodies can prevent broad HIV-1 antibodies from arising

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Luo, Shishi; Perelson, Alan S.

    2015-08-31

    The past decade has seen the discovery of numerous broad and potent monoclonal antibodies against HIV type 1 (HIV-1). Eliciting these antibodies via vaccination appears to be remarkably difficult, not least because they arise late in infection and are highly mutated relative to germline antibody sequences. Here, using a computational model, we show that broad antibodies could in fact emerge earlier and be less mutated, but that they may be prevented from doing so as a result of competitive exclusion by the autologous antibody response. We further find that this competitive exclusion is weaker in infections founded by multiple distinctmore » strains, with broadly neutralizing antibodies emerging earlier than in infections founded by a single strain. Our computational model simulates coevolving multitype virus and antibody populations. Broadly neutralizing antibodies may therefore be easier for the adaptive immune system to generate than previously thought. As a result, if less mutated broad antibodies exist, it may be possible to elicit them with a vaccine containing a mixture of diverse virus strains.« less

  12. Competitive exclusion by autologous antibodies can prevent broad HIV-1 antibodies from arising

    SciTech Connect (OSTI)

    Luo, Shishi; Perelson, Alan S.

    2015-08-31

    The past decade has seen the discovery of numerous broad and potent monoclonal antibodies against HIV type 1 (HIV-1). Eliciting these antibodies via vaccination appears to be remarkably difficult, not least because they arise late in infection and are highly mutated relative to germline antibody sequences. Here, using a computational model, we show that broad antibodies could in fact emerge earlier and be less mutated, but that they may be prevented from doing so as a result of competitive exclusion by the autologous antibody response. We further find that this competitive exclusion is weaker in infections founded by multiple distinct strains, with broadly neutralizing antibodies emerging earlier than in infections founded by a single strain. Our computational model simulates coevolving multitype virus and antibody populations. Broadly neutralizing antibodies may therefore be easier for the adaptive immune system to generate than previously thought. As a result, if less mutated broad antibodies exist, it may be possible to elicit them with a vaccine containing a mixture of diverse virus strains.

  13. Array of nucleic acid probes on biological chips for diagnosis of HIV and methods of using the same

    DOE Patents [OSTI]

    Chee, Mark (Palo Alto, CA); Gingeras, Thomas R. (Santa Clara, CA); Fodor, Stephen P. A. (Palo Alto, CA); Hubble, Earl A. (Mountain View, CA); Morris, MacDonald S. (San Jose, CA)

    1999-01-19

    The invention provides an array of oligonucleotide probes immobilized on a solid support for analysis of a target sequence from a human immunodeficiency virus. The array comprises at least four sets of oligonucleotide probes 9 to 21 nucleotides in length. A first probe set has a probe corresponding to each nucleotide in a reference sequence from a human immunodeficiency virus. A probe is related to its corresponding nucleotide by being exactly complementary to a subsequence of the reference sequence that includes the corresponding nucleotide. Thus, each probe has a position, designated an interrogation position, that is occupied by a complementary nucleotide to the corresponding nucleotide. The three additional probe sets each have a corresponding probe for each probe in the first probe set. Thus, for each nucleotide in the reference sequence, there are four corresponding probes, one from each of the probe sets. The three corresponding probes in the three additional probe sets are identical to the corresponding probe from the first probe or a subsequence thereof that includes the interrogation position, except that the interrogation position is occupied by a different nucleotide in each of the four corresponding probes.

  14. Recombinant soluble adenovirus receptor

    DOE Patents [OSTI]

    Freimuth, Paul I. (East Setauket, NY)

    2002-01-01

    Disclosed are isolated polypeptides from human CAR (coxsackievirus and adenovirus receptor) protein which bind adenovirus. Specifically disclosed are amino acid sequences which corresponds to adenovirus binding domain D1 and the entire extracellular domain of human CAR protein comprising D1 and D2. In other aspects, the disclosure relates to nucleic acid sequences encoding these domains as well as expression vectors which encode the domains and bacterial cells containing such vectors. Also disclosed is an isolated fusion protein comprised of the D1 polypeptide sequence fused to a polypeptide sequence which facilitates folding of D1 into a functional, soluble domain when expressed in bacteria. The functional D1 domain finds application for example in a therapeutic method for treating a patient infected with a virus which binds to D1, and also in a method for identifying an antiviral compound which interferes with viral attachment. Also included is a method for specifically targeting a cell for infection by a virus which binds to D1.

  15. The Structure of the Poxvirus A33 Protein Reveals a Dimer of Unique C-Type Lectin-Like Domains

    SciTech Connect (OSTI)

    Su, Hua-Poo; Singh, Kavita; Gittis, Apostolos G.; Garboczi, David N. (NIH)

    2010-11-03

    The current vaccine against smallpox is an infectious form of vaccinia virus that has significant side effects. Alternative vaccine approaches using recombinant viral proteins are being developed. A target of subunit vaccine strategies is the poxvirus protein A33, a conserved protein in the Chordopoxvirinae subfamily of Poxviridae that is expressed on the outer viral envelope. Here we have determined the structure of the A33 ectodomain of vaccinia virus. The structure revealed C-type lectin-like domains (CTLDs) that occur as dimers in A33 crystals with five different crystal lattices. Comparison of the A33 dimer models shows that the A33 monomers have a degree of flexibility in position within the dimer. Structural comparisons show that the A33 monomer is a close match to the Link module class of CTLDs but that the A33 dimer is most similar to the natural killer (NK)-cell receptor class of CTLDs. Structural data on Link modules and NK-cell receptor-ligand complexes suggest a surface of A33 that could interact with viral or host ligands. The dimer interface is well conserved in all known A33 sequences, indicating an important role for the A33 dimer. The structure indicates how previously described A33 mutations disrupt protein folding and locates the positions of N-linked glycosylations and the epitope of a protective antibody.

  16. Modelling hepatitis C therapy—predicting effects of treatment

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Perelson, Alan S.; Guedj, Jeremie

    2015-06-30

    Mathematically modelling changes in HCV RNA levels measured in patients who receive antiviral therapy has yielded many insights into the pathogenesis and effects of treatment on the virus. By determining how rapidly HCV is cleared when viral replication is interrupted by a therapy, one can deduce how rapidly the virus is produced in patients before treatment. This knowledge, coupled with estimates of the HCV mutation rate, enables one to estimate the frequency with which drug resistant variants arise. Modelling HCV also permits the deduction of the effectiveness of an antiviral agent at blocking HCV replication from the magnitude of themore » initial viral decline. One can also estimate the lifespan of an HCV-infected cell from the slope of the subsequent viral decline and determine the duration of therapy needed to cure infection. The original understanding of HCV RNA decline under interferon-based therapies obtained by modelling needed to be revised in order to interpret the HCV RNA decline kinetics seen when using direct-acting antiviral agents (DAAs). In addition, there also exist unresolved issues involving understanding therapies with combinations of DAAs, such as the presence of detectable HCV RNA at the end of therapy in patients who nonetheless have a sustained virologic response.« less

  17. Ecological succession and viability of human-associated microbiota on restroom surfaces

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Gibbons, Sean M.; Schwartz, Tara; Fouquier, Jennifer; Mitchell, Michelle; Sangwan, Naseer; Gilbert, Jack A.; Kelley, Scott T.; Elkins, C. A.

    2014-11-14

    Human-associated bacteria dominate the built environment (BE). Following decontamination of floors, toilet seats, and soap dispensers in four public restrooms, in situ bacterial communities were characterized hourly, daily, and weekly to determine their successional ecology. The viability of cultivable bacteria, following the removal of dispersal agents (humans), was also assessed hourly. A late-successional community developed within 5 to 8 h on restroom floors and showed remarkable stability over weeks to months. Despite late-successional dominance by skin- and outdoor-associated bacteria, the most ubiquitous organisms were predominantly gut-associated taxa, which persisted following exclusion of humans. Staphylococcus represented the majority of the cultivablemore » community, even after several hours of human exclusion. Methicillin-resistant Staphylococcus aureus (MRSA)-associated virulence genes were found on floors but were not present in assembled Staphylococcus pan-genomes. Viral abundances, which were predominantly enterophages, human papilloma virus, and herpesviruses, were significantly correlated with bacterial abundances and showed an unexpectedly low virus-to-bacterium ratio in surface-associated samples, suggesting that bacterial hosts are mostly dormant on BE surfaces.« less

  18. Tracing the HIV-1 subtype B mobility in Europe: a phylogeographic approach

    SciTech Connect (OSTI)

    Leitner, Thomas; Paraskevis, D; Pybus, O; Magiorkinis, G; Hatzakis, A

    2008-01-01

    The prevalence and the origin of HIV-1 subtype B, the most prevalent circulating clade among the long-term residents in Europe, have been studied extensively. However the spatial diffusion of the epidemic from the perspective of the virus has not previously been traced. In the current study we inferred the migration history of HIV-1 subtype B by way of a phylogeography of viral sequences sampled from 16 European countries and Israel. Migration events were inferred from viral phylogenies by character reconstruction using parsimony. With regard to the spatial dispersal of the HIV subtype B sequences across viral phylogenies, in most of the countries in Europe the epidemic was introduced by multiple sources and subsequently spread within local networks. Poland provides an exception where most of the infections were the result of a single point introduction. According to the significant migratory pathways, we show that there are considerable differences across Europe. Specifically, Greece, Portugal, Serbia and Spain, provide sources shedding HIV-1; Austria, Belgium and Luxembourg, on the other hand, are migratory targets, while for Denmark, Germany, Italy, Israel, Norway, the Netherlands, Sweden, Switzerland and the UK we inferred significant bidirectional migration. For Poland no significant migratory pathways were inferred. Subtype B phylogeographies provide a new insight about the geographical distribution of viral lineages, as well as the significant pathways of virus dispersal across Europe, suggesting that intervention strategies should also address tourists, travellers and migrants.

  19. Improved Bacterial and Viral Recoveries from 'Complex' Samples using Electrophoretically Assisted Acoustic Focusing

    SciTech Connect (OSTI)

    Ness, K; Rose, K; Jung, B; Fisher, K; Mariella, Jr., R P

    2008-03-27

    Automated front-end sample preparation technologies can significantly enhance the sensitivity and reliability of biodetection assays [1]. We are developing advanced sample preparation technologies for biowarfare detection and medical point-of-care diagnostics using microfluidic systems with continuous sample processing capabilities. Here we report an electrophoretically assisted acoustic focusing technique to rapidly extract and enrich viral and bacterial loads from 'complex samples', applied in this case to human nasopharyngeal samples as well as simplified surrogates. The acoustic forces capture and remove large particles (> 2 {micro}m) such as host cells, debris, dust, and pollen from the sample. We simultaneously apply an electric field transverse to the flow direction to transport small ({le} 2 {micro}m), negatively-charged analytes into a separate purified recovery fluid using a modified H-filter configuration [Micronics US Patent 5,716,852]. Hunter and O'Brien combined transverse electrophoresis and acoustic focusing to measure the surface charge on large particles, [2] but to our knowledge, our work is the first demonstration combining these two techniques in a continuous flow device. Marina et al. demonstrated superimposed dielectrophoresis (DEP) and acoustic focusing for enhanced separations [3], but these devices have limited throughput due to the rapid decay of DEP forces. Both acoustic standing waves and electric fields exert significant forces over the entire fluid volume in microchannels, thus allowing channels with larger dimensions (> 100 {micro}m) and high throughputs (10-100 {micro}L/min) necessary to process real-world volumes (1 mL). Previous work demonstrated acoustic focusing of microbeads [4] and biological species [5] in various geometries. We experimentally characterized our device by determining the biological size-cutoff where acoustic radiation pressure forces no longer transport biological particles. Figure 1 shows images of E.Coli ({approx}1 {micro}m) and yeast ({approx}4-5 {micro}m) flowing in a microchannel (200 {micro}m deep, 500 {micro}m wide) at a flow rate of 10 {micro}L/min. The E.Coli does not focus in the acoustic field while the yeast focuses at the channel centerline. This result suggests the acoustic size-cutoff for biological particles in our device lies between 2 and 3 {micro}m. Transverse electrophoresis has been explored extensively in electric field flow fractionation [6] and isoelectric focusing devices [7]. We demonstrated transverse electrophoretic transport of a wide variety of negatively-charged species, including fluorophores, beads, viruses, E.Coli, and yeast. Figure 2 shows the electromigration of a fluorescently labeled RNA virus (MS2) from the lower half of the channel to the upper half region with continuous flow. We demonstrated the effectiveness of our electrophoretically assisted acoustic focusing device by separating virus-like particles (40 nm fluorescent beads, selected to aid in visualization) from a high background concentration of yeast contaminants (see Figure 3). Our device allows for the efficient recovery of virus into a pre-selected purified buffer while background contaminants are acoustically captured and removed. We also tested the device using clinical nasopharyngeal samples, both washes and lavages, and demonstrated removal of unknown particulates (>2 ?m size) from the sample. Our future research direction includes spiking known amounts of bacteria and viruses into clinical samples and performing quantitative off-chip analysis (real-time PCR and flow cytometry).

  20. Colloqium on Pathogenes, to be held November 6-9, 2003 in Key Largo, FL

    SciTech Connect (OSTI)

    Richard J Roberts, PI; Karen C. Cone, Program Director and Report Preparer

    2004-01-01

    The American Academy of Microbiology convened a colloquium November 6-7, 2003, in Key Largo, Florida, to discuss the application of genomic methods to the study of pathogenesis. Professionals in the fields of genomics, bacteriology, virology, eukaryotic microbiology, medicine, clinical diagnostics, bioinformatics, and forensics contributed their expertise to discussions on the recent advancements in the field and the outlook for future research. A number of recommendations were made for ensuring that progress in the field continues. The availability of genome sequences from pathogenic bacteria, viruses, and fungi and other eukaryotes has opened new horizons for the field of pathogenesis. The genomes of over 100 bacterial pathogens have been fully sequenced, and scientists are busy investigating the mechanisms that regulate the diversity of bacterial pathogens and their myriad abilities to evade host defenses. Close to 1,200 viral genomes have been sequenced, and virologists are now beginning to examine the genomes of those viruses that cause undetected, cryptic infections. These virus-host interactions can serve as a reservoir of viral genes that later emerge in novel pathogens with the potential to infect humans, economically important animals, or crops. A number of eukaryotic microbes, including several pathogenic fungi, have also been sequenced, revealing unimagined diversity among these important pathogens. Certain themes have emerged from analyses of pathogen genome sequences, and the possibility exists that a sequence-based “common thread” may be found linking pathogens from different taxa. The results of genome sequencing efforts have also informed the study of pathogenesis, helping to identify the ways in which pathogens bring about disease. The advances of the past several years have been great, and we are closer than ever to a comprehensive understanding of pathogenesis, but much work lies ahead. If the science is to move forward, the genome sequences of many more organisms are needed. The sequences of many hosts, pathogens, their nonpathogenic relatives, commensals, as well as a diverse array of microorganisms, are all needed to complete the picture of pathogenesis and provide a phylogenetic framework for understanding the phenomenon. Moreover, improvements are needed in the two most important tools of genomics: annotation methodologies and sequence databases.

  1. HIV classification using coalescent theory

    SciTech Connect (OSTI)

    Zhang, Ming; Letiner, Thomas K; Korber, Bette T

    2008-01-01

    Algorithms for subtype classification and breakpoint detection of HIV-I sequences are based on a classification system of HIV-l. Hence, their quality highly depend on this system. Due to the history of creation of the current HIV-I nomenclature, the current one contains inconsistencies like: The phylogenetic distance between the subtype B and D is remarkably small compared with other pairs of subtypes. In fact, it is more like the distance of a pair of subsubtypes Robertson et al. (2000); Subtypes E and I do not exist any more since they were discovered to be composed of recombinants Robertson et al. (2000); It is currently discussed whether -- instead of CRF02 being a recombinant of subtype A and G -- subtype G should be designated as a circulating recombination form (CRF) nd CRF02 as a subtype Abecasis et al. (2007); There are 8 complete and over 400 partial HIV genomes in the LANL-database which belong neither to a subtype nor to a CRF (denoted by U). Moreover, the current classification system is somehow arbitrary like all complex classification systems that were created manually. To this end, it is desirable to deduce the classification system of HIV systematically by an algorithm. Of course, this problem is not restricted to HIV, but applies to all fast mutating and recombining viruses. Our work addresses the simpler subproblem to score classifications of given input sequences of some virus species (classification denotes a partition of the input sequences in several subtypes and CRFs). To this end, we reconstruct ancestral recombination graphs (ARG) of the input sequences under restrictions determined by the given classification. These restritions are imposed in order to ensure that the reconstructed ARGs do not contradict the classification under consideration. Then, we find the ARG with maximal probability by means of Markov Chain Monte Carlo methods. The probability of the most probable ARG is interpreted as a score for the classification. To our knowledge, this particular problem was not addressed up to now. The software package Lamarc Kuhner et al. (2000) allows for sampling ARGs, but it assumes that recombination events only involve one breakpoint. However, in HIV recombinants usually have more than one breakpoint. Moreover, Lamarc does not perform an explicit breakpoint detection, but tries to find them by chance. Although this approach is suitable for most situations, it will not lead to satisfying results in case of highly recombining viruses with multiple breakpoints.

  2. Mineralization and optical characterization of copper oxide nanoparticles using a high aspect ratio bio-template

    SciTech Connect (OSTI)

    Zaman, Mohammed Shahriar [Department of Electrical and Computer Engineering, University of California, Riverside, California 92521 (United States); Haberer, Elaine D., E-mail: haberer@ucr.edu [Department of Electrical and Computer Engineering, University of California, Riverside, California 92521 (United States); Materials Science and Engineering Program, University of California, Riverside, California 92521 (United States)

    2014-10-21

    Organized chains of copper oxide nanoparticles were synthesized, without palladium (Pd) activation, using the M13 filamentous virus as a biological template. The interaction of Cu precursor ions with the negatively charged viral coat proteins were studied with Fourier transform infrared spectroscopy, transmission electron microscopy, and energy dispersive x-ray spectroscopy. Discrete nanoparticles with an average diameter of 4.5 nm and narrow size distribution were closely spaced along the length of the high aspect ratio templates. The synthesized material was identified as a mixture of cubic Cu?O and monoclinic CuO. UV/Vis absorption measurements were completed and a direct optical band gap of 2.87 eV was determined using Tauc's method. This value was slightly larger than bulk, signaling quantum confinement effects within the templated materials.

  3. Cytoplasmic bacteriophage display system

    DOE Patents [OSTI]

    Studier, F. William; Rosenberg, Alan H.

    1998-06-16

    Disclosed are display vectors comprising DNA encoding a portion of a structural protein from a cytoplasmic bacteriophage, joined covalently to a protein or peptide of interest. Exemplified are display vectors wherein the structural protein is the T7 bacteriophage capsid protein. More specifically, in the exemplified display vectors the C-terminal amino acid residue of the portion of the capsid protein is joined to the N-terminal residue of the protein or peptide of interest. The portion of the T7 capsid protein exemplified comprises an N-terminal portion corresponding to form 10B of the T7 capsid protein. The display vectors are useful for high copy number display or lower copy number display (with larger fusion). Compositions of the type described herein are useful in connection with methods for producing a virus displaying a protein or peptide of interest.

  4. Cytoplasmic bacteriophage display system

    DOE Patents [OSTI]

    Studier, F.W.; Rosenberg, A.H.

    1998-06-16

    Disclosed are display vectors comprising DNA encoding a portion of a structural protein from a cytoplasmic bacteriophage, joined covalently to a protein or peptide of interest. Exemplified are display vectors wherein the structural protein is the T7 bacteriophage capsid protein. More specifically, in the exemplified display vectors the C-terminal amino acid residue of the portion of the capsid protein is joined to the N-terminal residue of the protein or peptide of interest. The portion of the T7 capsid protein exemplified comprises an N-terminal portion corresponding to form 10B of the T7 capsid protein. The display vectors are useful for high copy number display or lower copy number display (with larger fusion). Compositions of the type described herein are useful in connection with methods for producing a virus displaying a protein or peptide of interest. 1 fig.

  5. Three-dimensional Structure of a Viral Genome-delivery Portal Vertex

    SciTech Connect (OSTI)

    A Olia; P Prevelige Jr.; J Johnson; G Cingolani

    2011-12-31

    DNA viruses such as bacteriophages and herpesviruses deliver their genome into and out of the capsid through large proteinaceous assemblies, known as portal proteins. Here, we report two snapshots of the dodecameric portal protein of bacteriophage P22. The 3.25-{angstrom}-resolution structure of the portal-protein core bound to 12 copies of gene product 4 (gp4) reveals a {approx}1.1-MDa assembly formed by 24 proteins. Unexpectedly, a lower-resolution structure of the full-length portal protein unveils the unique topology of the C-terminal domain, which forms a {approx}200-{angstrom}-long {alpha}-helical barrel. This domain inserts deeply into the virion and is highly conserved in the Podoviridae family. We propose that the barrel domain facilitates genome spooling onto the interior surface of the capsid during genome packaging and, in analogy to a rifle barrel, increases the accuracy of genome ejection into the host cell.

  6. Apparatus and method for transforming living cells

    DOE Patents [OSTI]

    Okandan, Murat; Galambos, Paul C.

    2003-11-11

    An apparatus and method are disclosed for in vitro transformation of living cells. The apparatus, which is formed as a microelectromechanical device by surface micromachining, can be used to temporarily disrupt the cell walls or membrane of host cells one at a time so that a particular substance (e.g. a molecular tag, nucleic acid, bacteria, virus etc.) can be introduced into the cell. Disruption of the integrity of the host cells (i.e. poration) can be performed mechanically or electrically, or by both while the host cells are contained within a flow channel. Mechanical poration is possible using a moveable member which has a pointed or serrated edge and which is driven by an electrostatic actuator to abrade, impact or penetrate the host cell. Electroporation is produced by generating a relatively high electric field across the host cell when the host cell is located in the flow channel between a pair of electrodes having a voltage applied therebetween.

  7. Concentration and separation of biological organisms by ultrafiltration and dielectrophoresis

    DOE Patents [OSTI]

    Simmons, Blake A. (San Francisco, CA); Hill, Vincent R. (Decatur, GA); Fintschenko, Yolanda (Livermore, CA); Cummings, Eric B. (Livermore, CA)

    2010-10-12

    Disclosed is a method for monitoring sources of public water supply for a variety of pathogens by using a combination of ultrafiltration techniques together dielectrophoretic separation techniques. Because water-borne pathogens, whether present due to "natural" contamination or intentional introduction, would likely be present in drinking water at low concentrations when samples are collected for monitoring or outbreak investigations, an approach is needed to quickly and efficiently concentrate and separate particles such as viruses, bacteria, and parasites in large volumes of water (e.g., 100 L or more) while simultaneously reducing the sample volume to levels sufficient for detecting low concentrations of microbes (e.g., <10 mL). The technique is also designed to screen the separated microbes based on specific conductivity and size.

  8. Evidence of an oncogenic gammaherpesvirus in domestic dogs

    SciTech Connect (OSTI)

    Huang, Shih-Hung; Kozak, Philip J.; Kim, Jessica; Habineza-Ndikuyeze, Georges; Meade, Charles; Gaurnier-Hausser, Anita; Patel, Reema; Robertson, Erle; and others

    2012-06-05

    In humans, chronic infection with the gammaherpesvirus Epstein-Barr virus is usually asymptomatic; however some infected individuals develop hematological and epithelial malignancies. The exact role of EBV in lymphomagenesis is poorly understood partly because of the lack of clinically relevant animal models. Here we report the detection of serological responses against EBV capsid antigens in healthy dogs and dogs with spontaneous lymphoma and that dogs with the highest antibody titers have B cell lymphoma. Moreover, we demonstrate the presence of EBV-like viral DNA and RNA sequences and Latent Membrane Protein-1 in malignant lymph nodes of dogs with lymphoma. Finally, electron microscopy of canine malignant B cells revealed the presence of classic herpesvirus particles. These findings suggest that dogs can be naturally infected with an EBV-like gammaherpesvirus that may contribute to lymphomagenesis and that dogs might represent a spontaneous model to investigate environmental and genetic factors that influence gammaherpesvirus-associated lymphomagenesis in humans.

  9. Putting the Squeeze on Biology: Biomolecules Under Pressure

    ScienceCinema (OSTI)

    Sol Gruner

    2010-01-08

    Modest pressures encountered in the biosphere (i.e., below a few kbar) have extraordinary effects on biomembranes and proteins. These include pressure denaturation of proteins, dramatic changes in protein-protein association, substrate binding, membrane ion transport, DNA transcription, virus infectivity, and enzyme kinetics. Yet all of the biomaterials involved are highly incompressible. The challenge to the physicist is to understand the structural coupling between these effects and pressure to elucidate the relevant mechanisms. X-ray diffraction studies of membranes and proteins under pressure will be described. It is seen that it is not so much the magnitude of the changes, but rather the differential compressibilities of different parts of the structure that are responsible for effects.

  10. 2011 Archaea: Ecology, Metabolism, & Molecular Biology

    SciTech Connect (OSTI)

    Keneth Stedman

    2011-08-05

    Archaea, one of three major evolutionary lineages of life, are a fascinating and diverse group of microbes with deep roots overlapping those of eukaryotes. The focus of the 'Archaea: Ecology Metabolism & Molecular Biology' GRC conference expands on a number of emerging topics highlighting new paradigms in archaeal metabolism, genome function and systems biology; information processing; evolution and the tree of life; the ecology and diversity of archaea and their viruses. The strength of this conference lies in its ability to couple a field with a rich history in high quality research with new scientific findings in an atmosphere of stimulating exchange. This conference remains an excellent opportunity for younger scientists to interact with world experts in this field.

  11. The Integrated Microbial Genomes (IMG) System: An Expanding Comparative Analysis Resource

    SciTech Connect (OSTI)

    Markowitz, Victor M.; Chen, I-Min A.; Palaniappan, Krishna; Chu, Ken; Szeto, Ernest; Grechkin, Yuri; Ratner, Anna; Anderson, Iain; Lykidis, Athanasios; Mavromatis, Konstantinos; Ivanova, Natalia N.; Kyrpides, Nikos C.

    2009-09-13

    The integrated microbial genomes (IMG) system serves as a community resource for comparative analysis of publicly available genomes in a comprehensive integrated context. IMG contains both draft and complete microbial genomes integrated with other publicly available genomes from all three domains of life, together with a large number of plasmids and viruses. IMG provides tools and viewers for analyzing and reviewing the annotations of genes and genomes in a comparative context. Since its first release in 2005, IMG's data content and analytical capabilities have been constantly expanded through regular releases. Several companion IMG systems have been set up in order to serve domain specific needs, such as expert review of genome annotations. IMG is available at .

  12. F{sub o}F{sub 1}-ATPase activity regulated by external links on {beta} subunits

    SciTech Connect (OSTI)

    Cheng, Jie; Zhang, Xiao-ai; Graduate School of the Chinese Academy of Sciences, Beijing 100049 ; Shu, Yao-Gen; Yue, Jia-Chang

    2010-01-01

    F{sub o}F{sub 1}-ATPase activity is regulated by external links on {beta} subunits with different molecular weight. It is inhibited when anti-{beta} subunit antibody, streptavidin and H9 antibody link on the {beta} subunits successively, but is activated when virus was binded. Western blotting indicated that the employed anti-{beta} antibody target was on the non-catalytic site of the {beta} subunit. Furthermore, an ESR study of spin-labeled ATP (SL-ATP) showed that the affinity of ATP to the holoenzyme increases with increasing external links on the {beta} subunits. This simple regulation method may have great potential in the design of rapid, free labeled, sensitive and selective biosensors.

  13. Method for concentration and separation of biological organisms by ultrafiltration and dielectrophoresis

    DOE Patents [OSTI]

    Simmons, Blake A.; Hill, Vincent R.; Fintschenko, Yolanda; Cummings, Eric B.

    2012-09-04

    Disclosed is a method for monitoring sources of public water supply for a variety of pathogens by using a combination of ultrafiltration techniques together dielectrophoretic separation techniques. Because water-borne pathogens, whether present due to "natural" contamination or intentional introduction, would likely be present in drinking water at low concentrations when samples are collected for monitoring or outbreak investigations, an approach is needed to quickly and efficiently concentrate and separate particles such as viruses, bacteria, and parasites in large volumes of water (e.g., 100 L or more) while simultaneously reducing the sample volume to levels sufficient for detecting low concentrations of microbes (e.g., <10 mL). The technique is also designed to screen the separated microbes based on specific conductivity and size.

  14. Flow-controlled magnetic particle manipulation

    DOE Patents [OSTI]

    Grate, Jay W [West Richland, WA; Bruckner-Lea, Cynthia J [Richland, WA; Holman, David A [Las Vegas, NV

    2011-02-22

    Inventive methods and apparatus are useful for collecting magnetic materials in one or more magnetic fields and resuspending the particles into a dispersion medium, and optionally repeating collection/resuspension one or more times in the same or a different medium, by controlling the direction and rate of fluid flow through a fluid flow path. The methods provide for contacting derivatized particles with test samples and reagents, removal of excess reagent, washing of magnetic material, and resuspension for analysis, among other uses. The methods are applicable to a wide variety of chemical and biological materials that are susceptible to magnetic labeling, including, for example, cells, viruses, oligonucleotides, proteins, hormones, receptor-ligand complexes, environmental contaminants and the like.

  15. 2009 Archaea: Ecology, Metabolism & Molecular Biology GRC

    SciTech Connect (OSTI)

    Dr. Julie Maupin- Furlow

    2009-07-26

    Archaea, one of three major evolutionary lineages of life, are a fascinating and diverse group of microbes with deep roots overlapping those of eukaryotes. The focus of the 'Archaea: Ecology Metabolism & Molecular Biology' GRC conference expands on a number of emerging topics highlighting new paradigms in archaeal metabolism, genome function and systems biology; information processing; evolution and the tree of life; the ecology and diversity of archaea and their viruses; and industrial applications. The strength of this conference lies in its ability to couple a field with a rich history in high quality research with new scientific findings in an atmosphere of stimulating exchange. This conference remains an excellent opportunity for younger scientists to interact with world experts in this field.

  16. Science and Technology Review December 2009

    SciTech Connect (OSTI)

    Bearinger, J P

    2009-11-17

    This month's issue has the following articles: (1) Advanced Materials for Our Past, Present, and Future - Commentary by Tomas Diaz de la Rubia; (2) A Defensive 'Coat' for Materials under Attack - Amorphous metal coatings provide the strength and corrosion resistance needed to protect military vessels and spent nuclear fuel containers; (3) Too Close for Comfort - Laboratory scientists are analyzing the feasibility of using nuclear explosives to disrupt or divert asteroids on a collision course with Earth; (4) Hyperion: A Titan of High-Performance Computing Systems - Livermore is collaborating with 10 computing industry leaders to create a test bed for Linux cluster hardware and software technologies; (5) Isolating Pathogens for Speedy Identification - An automated miniature device separates viruses, bacteria, genetic material, and proteins from nasal swabs and blood and urine samples for speedy identification.

  17. Sabin-to-Mahoney Transition Model of Quasispecies Replication

    Energy Science and Technology Software Center (OSTI)

    2009-05-31

    Qspp is an agent-based stochastic simulation model of the Poliovirus Sabin-to-Mahoney transition. This code simulates a cell-to-cell model of Poliovirus replication. The model tracks genotypes (virus genomes) as they are replicated in cells, and as the cells burst and release particles into the medium of a culture dish. An inoculum is then taken from the pool of virions and is used to inoculate cells on a new dish. This process repeats. The Sabin genotype comprisesmore » the initial inoculum. Nucleotide positions that match the Sabin1 (vaccine strain) and Mahoney (wild type) genotypes, as well as the neurovirulent phenotype (from the literature) are enumerated as constants.« less

  18. Science and Technology Review December 2010

    SciTech Connect (OSTI)

    Blobaum, K M

    2010-10-29

    This month's issue has the following articles: (1) More Insight to Better Understand Climate Change - Commentary by Tomas Diaz de la Rubia; (2) Strengthening Our Understanding of Climate Change - Researchers at the Center for Accelerator Mass Spectrometry are working to better understand climate variation and sharpen the accuracy of predictive models; (3) Precision Diagnostics Tell All - The National Ignition Facility relies on sophisticated diagnostic instruments for measuring the key physical processes that occur in high-energy-density experiments; (4) Quick Detection of Pathogens by the Thousands - Livermore scientists have developed a device that can simultaneously identify thousands of viruses and bacteria within 24 hours; and (5) Carbon Dioxide into the Briny Deep - A proposed technique for burying carbon dioxide underground could help mitigate the effects of this greenhouse gas while producing freshwater.

  19. APPLICATIONS OF LAYERED DOUBLE HYDROXIDES IN REMOVING OXYANIONS FROM OIL REFINING AND COAL MINING WASTEWATER

    SciTech Connect (OSTI)

    Song Jin; Paul Fallgren

    2006-03-01

    Western Research Institute (WRI), in conjunction with the U.S. Department of Energy (DOE), conducted a study of using the layered double hydroxides (LDH) as filter material to remove microorganisms, large biological molecules, certain anions and toxic oxyanions from various waste streams, including wastewater from refineries. Results demonstrate that LDH has a high adsorbing capability to those compounds with negative surface charge. Constituents studied include model bacteria, viruses, arsenic, selenium, vanadium, diesel range hydrocarbons, methyl tert-butyl ether (MTBE), mixed petroleum constituents, humic materials and anions. This project also attempted to modify the physical structure of LDH for the application as a filtration material. Flow characterizations of the modified LDH materials were also investigated. Results to date indicate that LDH is a cost-effective new material to be used for wastewater treatment, especially for the treatment of anions and oxyanions.

  20. SLAC All Access: Atomic, Molecular and Optical Science Instrument

    ScienceCinema (OSTI)

    Bozek, John

    2014-06-03

    John Bozek, a staff scientist at SLAC's Linac Coherent Light Source (LCLS) X-ray laser who manages the LCLS Soft X-ray Department, takes us behind the scenes at the Atomic, Molecular and Optical Science (AMO) instrument, the first of six experimental stations now operating at LCLS. Samples used in AMO experiments include atoms, molecules, clusters, and nanoscale objects such as protein crystals or viruses. Science performed at AMO includes fundamental studies of light-matter interactions in the extreme X-ray intensity of the LCLS pules, time-resolved studies of increasingly charged states of atoms and molecules, X-ray diffraction imaging of nanocrystals, and single-shot imaging of a variety of objects.