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  • Spacecraft Design, Testing and Performance  (16)
  • Humans  (6)
  • 2005-2009  (22)
  • 1970-1974
  • 1935-1939
  • 1
    Publication Date: 2008-05-16
    Description: The potential impact of pandemic influenza makes effective measures to limit the spread and morbidity of virus infection a public health priority. Antiviral drugs are seen as essential requirements for control of initial influenza outbreaks caused by a new virus, and in pre-pandemic plans there is a heavy reliance on drug stockpiles. The principal target for these drugs is a virus surface glycoprotein, neuraminidase, which facilitates the release of nascent virus and thus the spread of infection. Oseltamivir (Tamiflu) and zanamivir (Relenza) are two currently used neuraminidase inhibitors that were developed using knowledge of the enzyme structure. It has been proposed that the closer such inhibitors resemble the natural substrate, the less likely they are to select drug-resistant mutant viruses that retain viability. However, there have been reports of drug-resistant mutant selection in vitro and from infected humans. We report here the enzymatic properties and crystal structures of neuraminidase mutants from H5N1-infected patients that explain the molecular basis of resistance. Our results show that these mutants are resistant to oseltamivir but still strongly inhibited by zanamivir owing to an altered hydrophobic pocket in the active site of the enzyme required for oseltamivir binding. Together with recent reports of the viability and pathogenesis of H5N1 (ref. 7) and H1N1 (ref. 8) viruses with neuraminidases carrying these mutations, our results indicate that it would be prudent for pandemic stockpiles of oseltamivir to be augmented by additional antiviral drugs, including zanamivir.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Collins, Patrick J -- Haire, Lesley F -- Lin, Yi Pu -- Liu, Junfeng -- Russell, Rupert J -- Walker, Philip A -- Skehel, John J -- Martin, Stephen R -- Hay, Alan J -- Gamblin, Steven J -- MC_U117512711/Medical Research Council/United Kingdom -- MC_U117512723/Medical Research Council/United Kingdom -- MC_U117570592/Medical Research Council/United Kingdom -- MC_U117584222/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- England -- Nature. 2008 Jun 26;453(7199):1258-61. doi: 10.1038/nature06956. Epub 2008 May 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MRC-National Institute for Medical Research, Mill Hill, London NW7 1AA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18480754" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Crystallography, X-Ray ; *Drug Resistance, Viral ; Enzyme Inhibitors/chemistry/metabolism/pharmacology ; Humans ; Influenza A Virus, H1N1 Subtype/drug effects/enzymology/genetics ; Influenza A Virus, H5N1 Subtype/*drug effects/*enzymology/genetics ; Influenza, Human/virology ; Kinetics ; Models, Molecular ; Molecular Conformation ; Mutation/*genetics ; Neuraminidase/antagonists & inhibitors/*chemistry/*genetics/metabolism ; Oseltamivir/chemistry/metabolism/*pharmacology ; Protein Binding ; Zanamivir/pharmacology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2009-08-04
    Description: Polymerization of actin filaments directed by the actin-related protein (Arp)2/3 complex supports many types of cellular movements. However, questions remain regarding the relative contributions of Arp2/3 complex versus other mechanisms of actin filament nucleation to processes such as path finding by neuronal growth cones; this is because of the lack of simple methods to inhibit Arp2/3 complex reversibly in living cells. Here we describe two classes of small molecules that bind to different sites on the Arp2/3 complex and inhibit its ability to nucleate actin filaments. CK-0944636 binds between Arp2 and Arp3, where it appears to block movement of Arp2 and Arp3 into their active conformation. CK-0993548 inserts into the hydrophobic core of Arp3 and alters its conformation. Both classes of compounds inhibit formation of actin filament comet tails by Listeria and podosomes by monocytes. Two inhibitors with different mechanisms of action provide a powerful approach for studying the Arp2/3 complex in living cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2780427/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2780427/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nolen, B J -- Tomasevic, N -- Russell, A -- Pierce, D W -- Jia, Z -- McCormick, C D -- Hartman, J -- Sakowicz, R -- Pollard, T D -- F32 GM074374-02/GM/NIGMS NIH HHS/ -- GM-066311/GM/NIGMS NIH HHS/ -- GM074374-02/GM/NIGMS NIH HHS/ -- P01 GM066311/GM/NIGMS NIH HHS/ -- P01 GM066311-01A1/GM/NIGMS NIH HHS/ -- P30 EB009998/EB/NIBIB NIH HHS/ -- England -- Nature. 2009 Aug 20;460(7258):1031-4. doi: 10.1038/nature08231. Epub 2009 Aug 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19648907" target="_blank"〉PubMed〈/a〉
    Keywords: Actin Cytoskeleton/drug effects/metabolism ; Actin-Related Protein 2/antagonists & inhibitors/chemistry/metabolism ; Actin-Related Protein 2-3 Complex/*antagonists & inhibitors/chemistry/metabolism ; Actin-Related Protein 3/antagonists & inhibitors/chemistry/metabolism ; Actins/chemistry/metabolism ; Animals ; Biopolymers/chemistry/metabolism ; Cattle ; Cell Line ; Crystallography, X-Ray ; Humans ; Hydrophobic and Hydrophilic Interactions ; Indoles/classification/metabolism/pharmacology ; Listeria/physiology ; Models, Molecular ; Monocytes/immunology ; Protein Conformation/drug effects ; Schizosaccharomyces ; Thiazoles/chemistry/classification/metabolism/pharmacology ; Thiophenes/classification/metabolism/pharmacology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2007-12-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Denofrio, Lauren A -- Russell, Brandy -- Lopatto, David -- Lu, Yi -- New York, N.Y. -- Science. 2007 Dec 21;318(5858):1872-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18096791" target="_blank"〉PubMed〈/a〉
    Keywords: Biological Science Disciplines/*education ; Chemistry/*education ; *Curriculum ; Humans ; *Mentors ; Teaching/*methods
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2008-04-19
    Description: Antigenic and genetic analysis of the hemagglutinin of approximately 13,000 human influenza A (H3N2) viruses from six continents during 2002-2007 revealed that there was continuous circulation in east and Southeast Asia (E-SE Asia) via a region-wide network of temporally overlapping epidemics and that epidemics in the temperate regions were seeded from this network each year. Seed strains generally first reached Oceania, North America, and Europe, and later South America. This evidence suggests that once A (H3N2) viruses leave E-SE Asia, they are unlikely to contribute to long-term viral evolution. If the trends observed during this period are an accurate representation of overall patterns of spread, then the antigenic characteristics of A (H3N2) viruses outside E-SE Asia may be forecast each year based on surveillance within E-SE Asia, with consequent improvements to vaccine strain selection.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Russell, Colin A -- Jones, Terry C -- Barr, Ian G -- Cox, Nancy J -- Garten, Rebecca J -- Gregory, Vicky -- Gust, Ian D -- Hampson, Alan W -- Hay, Alan J -- Hurt, Aeron C -- de Jong, Jan C -- Kelso, Anne -- Klimov, Alexander I -- Kageyama, Tsutomu -- Komadina, Naomi -- Lapedes, Alan S -- Lin, Yi P -- Mosterin, Ana -- Obuchi, Masatsugu -- Odagiri, Takato -- Osterhaus, Albert D M E -- Rimmelzwaan, Guus F -- Shaw, Michael W -- Skepner, Eugene -- Stohr, Klaus -- Tashiro, Masato -- Fouchier, Ron A M -- Smith, Derek J -- DP1-OD000490-01/OD/NIH HHS/ -- MC_U117512723/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2008 Apr 18;320(5874):340-6. doi: 10.1126/science.1154137.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Zoology, University of Cambridge, Cambridge, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18420927" target="_blank"〉PubMed〈/a〉
    Keywords: Antigenic Variation ; Asia/epidemiology ; Asia, Southeastern/epidemiology ; *Disease Outbreaks ; Europe/epidemiology ; Evolution, Molecular ; Forecasting ; Hemagglutinin Glycoproteins, Influenza Virus/genetics/*immunology ; Humans ; *Influenza A Virus, H3N2 Subtype/classification/genetics/immunology/isolation & ; purification ; Influenza Vaccines ; Influenza, Human/*epidemiology/virology ; North America/epidemiology ; Oceania ; Phylogeny ; Population Surveillance ; Seasons ; South America/epidemiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2008-08-30
    Description: The archaeology of pre-Columbian polities in the Amazon River basin forces a reconsideration of early urbanism and long-term change in tropical forest landscapes. We describe settlement and land-use patterns of complex societies on the eve of European contact (after 1492) in the Upper Xingu region of the Brazilian Amazon. These societies were organized in articulated clusters, representing small independent polities, within a regional peer polity. These patterns constitute a "galactic" form of prehistoric urbanism, sharing features with small-scale urban polities in other areas. Understanding long-term change in coupled human-environment systems relating to these societies has implications for conservation and sustainable development, notably to control ecological degradation and maintain regional biodiversity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Heckenberger, Michael J -- Russell, J Christian -- Fausto, Carlos -- Toney, Joshua R -- Schmidt, Morgan J -- Pereira, Edithe -- Franchetto, Bruna -- Kuikuro, Afukaka -- New York, N.Y. -- Science. 2008 Aug 29;321(5893):1214-7. doi: 10.1126/science.1159769.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Anthropology, University of Florida, Gainesville, FL 32611, USA. mheck@ufl.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18755979" target="_blank"〉PubMed〈/a〉
    Keywords: Agriculture/history ; *Archaeology ; Biodiversity ; Brazil ; Cities/*history ; *Culture ; Ecosystem ; Environment Design ; History, Ancient ; Humans ; Residence Characteristics ; Rivers ; *Trees
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2009-05-26
    Description: Since its identification in April 2009, an A(H1N1) virus containing a unique combination of gene segments from both North American and Eurasian swine lineages has continued to circulate in humans. The lack of similarity between the 2009 A(H1N1) virus and its nearest relatives indicates that its gene segments have been circulating undetected for an extended period. Its low genetic diversity suggests that the introduction into humans was a single event or multiple events of similar viruses. Molecular markers predictive of adaptation to humans are not currently present in 2009 A(H1N1) viruses, suggesting that previously unrecognized molecular determinants could be responsible for the transmission among humans. Antigenically the viruses are homogeneous and similar to North American swine A(H1N1) viruses but distinct from seasonal human A(H1N1).〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3250984/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3250984/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Garten, Rebecca J -- Davis, C Todd -- Russell, Colin A -- Shu, Bo -- Lindstrom, Stephen -- Balish, Amanda -- Sessions, Wendy M -- Xu, Xiyan -- Skepner, Eugene -- Deyde, Varough -- Okomo-Adhiambo, Margaret -- Gubareva, Larisa -- Barnes, John -- Smith, Catherine B -- Emery, Shannon L -- Hillman, Michael J -- Rivailler, Pierre -- Smagala, James -- de Graaf, Miranda -- Burke, David F -- Fouchier, Ron A M -- Pappas, Claudia -- Alpuche-Aranda, Celia M -- Lopez-Gatell, Hugo -- Olivera, Hiram -- Lopez, Irma -- Myers, Christopher A -- Faix, Dennis -- Blair, Patrick J -- Yu, Cindy -- Keene, Kimberly M -- Dotson, P David Jr -- Boxrud, David -- Sambol, Anthony R -- Abid, Syed H -- St George, Kirsten -- Bannerman, Tammy -- Moore, Amanda L -- Stringer, David J -- Blevins, Patricia -- Demmler-Harrison, Gail J -- Ginsberg, Michele -- Kriner, Paula -- Waterman, Steve -- Smole, Sandra -- Guevara, Hugo F -- Belongia, Edward A -- Clark, Patricia A -- Beatrice, Sara T -- Donis, Ruben -- Katz, Jacqueline -- Finelli, Lyn -- Bridges, Carolyn B -- Shaw, Michael -- Jernigan, Daniel B -- Uyeki, Timothy M -- Smith, Derek J -- Klimov, Alexander I -- Cox, Nancy J -- DP1 OD000490-01/OD/NIH HHS/ -- DP1-OD000490-01/OD/NIH HHS/ -- HHSN266200700010C/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2009 Jul 10;325(5937):197-201. doi: 10.1126/science.1176225. Epub 2009 May 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉WHO Collaborating Center for Influenza, Centers for Disease Control and Prevention (CDC), Atlanta, GA 30333, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19465683" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Viral/immunology ; Antigens, Viral/genetics/*immunology ; Disease Outbreaks ; Evolution, Molecular ; Genes, Viral ; Genetic Variation ; Genome, Viral ; Hemagglutination Inhibition Tests ; Hemagglutinin Glycoproteins, Influenza Virus/chemistry/genetics/immunology ; Humans ; Influenza A Virus, H1N1 Subtype/classification/*genetics/*immunology/isolation & ; purification ; Influenza A Virus, H3N2 Subtype/genetics ; Influenza A virus/genetics ; Influenza, Human/epidemiology/immunology/*virology ; Mutation ; Neuraminidase/genetics ; Orthomyxoviridae Infections/veterinary/virology ; Phylogeny ; Reassortant Viruses/genetics ; Swine ; Swine Diseases/virology ; Viral Matrix Proteins/genetics ; Viral Nonstructural Proteins/genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2018-06-06
    Description: The use of spacecraft formations creates new and more demanding requirements for orbit determination accuracy. In addition to absolute navigation requirements, there are typically relative navigation requirements that are based on the size or shape of the formation. The difficulty in meeting these requirements is related to the relative dynamics of the spacecraft orbits and the frequency of the formation maintenance maneuvers. This paper examines the effects of bi-weekly formation maintenance maneuvers on the absolute and relative orbit determination accuracy for the four-spacecraft Magnetospheric Multiscale (MMS) formation. Results are presented from high fidelity simulations that include the effects of realistic orbit determination errors in the maneuver planning process. Solutions are determined using a high accuracy extended Kalman filter designed for onboard navigation. Three different solutions are examined, considering the effects of process noise and measurement rate on the solutions.
    Keywords: Spacecraft Design, Testing and Performance
    Type: Proceedings of the 20th International Symposium on Space Flight Dynamics; NASA/CP-2007-214158
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  • 8
    Publication Date: 2019-07-18
    Description: In this paper, we present in situ observations of surface waves at the magnetopause and oscillatory magnetospheric field lines, and coordinated observations Pc5 waves at geosynchronous orbit by the GOES spacecraft, and on the ground by CANOPUS and 210 Degree Magnetic Meridian (210MMJ magnetometer arrays. On February 7,2002 during a highspeed solar wind stream, the Polar spacecraft was skimming the magnetopause in a post-noon meridian plane for approximately 3 hours. During this interval, it made two short excursions and a few partial crossings into the magnetosheath and observed quasi-periodic cold ion bursts in the region adjacent to the magnetopause current layer. The multiple magnetopause crossings as well as the velocity of the cold ion bursts indicate that the magnetopause was oscillating with about 6 minute period. Simultaneous observations of Pc5 waves at geosynchronous orbit by the GOES spacecraft and on the ground by the CANOPUS magnetometer array reveal that these magnetospheric pulsations were forced oscillations of magnetic field lines directly driven by the magnetopause oscillations. The magnetospheric pulsations occurred only in a limited longitudinal region in the post-noon dayside sector, and were not a global phenomenon as one would expect for global field line resonance. Thus, the magnetopause oscillations at the source were also limited to a localized region spanning about 4 hours in local time.
    Keywords: Spacecraft Design, Testing and Performance
    Type: 2005 Chapman Conference on Magnetospheric ULF Waves; Mar 21, 2005 - Mar 25, 2005; San Diego, CA; United States
    Format: text
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  • 9
    Publication Date: 2019-07-13
    Description: Orion is the next vehicle for human space travel. Humans will be sustained in space by the Orion subystem, environmental control and life support (ECLS). The ECLS concept at the subsystem level is outlined by function and technology. In the past two years, the interface definition with other subsystems has increased through different integrated studies. The paper presents the key requirements and discusses three recent studies (e.g., unpressurized cargo) along with the respective impacts on the ECLS design moving forward.
    Keywords: Spacecraft Design, Testing and Performance
    Type: SAE-08ICES-01-0198 , JSC-CN-15794 , International Conference on Environmental Sciences; Jun 30, 2008 - Jul 03, 2008; San Francisco, CA; United States
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  • 10
    Publication Date: 2019-07-13
    Description: The United States Space Operational Space Shuttle Fleet Consists of three shuttles with an average age of 19.7 years. Shuttles are exposed to corrosive conditions while undergoing final closeout for missions at the launch pad and extreme conditions during ascent, orbit, and descent that may accelerate the corrosion process. Structural corrosion under TPS could progress undetected (without tile removal) and eventually result in reduction in structural capability sufficient to create negative margins of . safety and ultimate loss of local structural capability.
    Keywords: Spacecraft Design, Testing and Performance
    Type: KSC-2007-054 , Aging Aircraft 2007; Apr 16, 2007 - Apr 19, 2007; Palm Springs, CA; United States
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