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  • 1
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    [Review] Latency reversal and viral clearance to cure HIV-1 (2016)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2016-07-22
    Description: Research toward a cure for human immunodeficiency virus type 1 (HIV-1) infection has joined prevention and treatment efforts in the global public health agenda. A major approach to HIV eradication envisions antiretroviral suppression, paired with targeted therapies to enforce the expression of viral antigen from quiescent HIV-1 genomes, and immunotherapies to clear latent infection. These strategies are targeted to lead to viral eradication—a cure for AIDS. Paired testing of latency reversal and clearance strategies has begun, but additional obstacles to HIV eradication may emerge. Nevertheless, there is reason for optimism that advances in long-acting antiretroviral therapy and HIV prevention strategies will contribute to efforts in HIV cure research and that the implementation of these efforts will synergize to markedly blunt the effect of the HIV pandemic on society. Authors: David M. Margolis, J. Victor Garcia, Daria J. Hazuda, Barton F. Haynes
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    HIV reservoirs: what, where and how to target them (2015)
    Springer Nature
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    Publication Date: 2015-12-12
    Description: Nature Reviews Microbiology 14, 55 (2016). doi:10.1038/nrmicro.2015.5 Authors: Melissa J. Churchill, Steven G. Deeks, David M. Margolis, Robert F. Siliciano & Ronald Swanstrom One of the main challenges in the fight against HIV infection is to develop strategies that are able to eliminate the persistent viral reservoir that harbours integrated, replication-competent provirus within host cellular DNA. This reservoir is resistant to antiretroviral therapy (ART) and to clearance by
    Print ISSN: 1740-1526
    Electronic ISSN: 1740-1534
    Topics: Biology , Medicine
    Published by Springer Nature
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  • 3
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    Eradicating HIV-1 infection: seeking to clear a persistent pathogen (2014)
    Springer Nature
    Details
    Publication Date: 2014-10-17
    Description: Nature Reviews Microbiology 12, 750 (2014). doi:10.1038/nrmicro3352 Authors: Nancie M. Archin, Julia Marsh Sung, Carolina Garrido, Natalia Soriano-Sarabia & David M. Margolis Effective antiretroviral therapy (ART) blunts viraemia, which enables HIV-1-infected individuals to control infection and live long, productive lives. However, HIV-1 infection remains incurable owing to the persistence of a viral reservoir that harbours integrated provirus within host cellular DNA. This latent infection is unaffected by
    Print ISSN: 1740-1526
    Electronic ISSN: 1740-1534
    Topics: Biology , Medicine
    Published by Springer Nature
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  • 4
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    Temperature oscillations in the north atlantic (2007)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2007-09-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schlesinger, M E -- Ramankutty, N -- Andronova, N -- Margolis, M -- Kerr, R A -- New York, N.Y. -- Science. 2000 Jul 28;289(5479):547b-8b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17832062" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 5
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    Underinvestment: the energy technology and R&D policy challenge (1999)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1999-07-31
    Description: This Viewpoint examines data on international trends in energy research and development (R&D) funding, patterns of U.S. energy technology patents and R&D funding, and U.S. R&D intensities across selected sectors. The data present a disturbing picture: (i) Energy technology funding levels have declined significantly during the past two decades throughout the industrial world; (ii) U.S. R&D spending and patents, both overall and in the energy sector, have been highly correlated during the past two decades; and (iii) the R&D intensity of the U.S. energy sector is extremely low. It is argued that recent cutbacks in energy R&D are likely to reduce the capacity of the energy sector to innovate. The trends are particularly troubling given the need for increased international capacity to respond to emerging risks such as global climate change.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Margolis -- Kammen -- New York, N.Y. -- Science. 1999 Jul 30;285(5428):690-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Science, Technology and Environmental Policy (STEP) Program, Woodrow Wilson School of Public and International Affairs, Princeton University, Princeton, NJ 08544-1013, USA. Energy and Resources Group (ERG), University of California, Berkele.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10426983" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 6
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    Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-07-28
    Description: Despite antiretroviral therapy, proviral latency of human immunodeficiency virus type 1 (HIV-1) remains a principal obstacle to curing the infection. Inducing the expression of latent genomes within resting CD4(+) T cells is the primary strategy to clear this reservoir. Although histone deacetylase inhibitors such as suberoylanilide hydroxamic acid (also known as vorinostat, VOR) can disrupt HIV-1 latency in vitro, the utility of this approach has never been directly proven in a translational clinical study of HIV-infected patients. Here we isolated the circulating resting CD4(+) T cells of patients in whom viraemia was fully suppressed by antiretroviral therapy, and directly studied the effect of VOR on this latent reservoir. In each of eight patients, a single dose of VOR increased both biomarkers of cellular acetylation, and simultaneously induced an increase in HIV RNA expression in resting CD4(+) cells (mean increase, 4.8-fold). This demonstrates that a molecular mechanism known to enforce HIV latency can be therapeutically targeted in humans, provides proof-of-concept for histone deacetylase inhibitors as a therapeutic class, and defines a precise approach to test novel strategies to attack and eradicate latent HIV infection directly.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3704185/" 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/PMC3704185/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Archin, N M -- Liberty, A L -- Kashuba, A D -- Choudhary, S K -- Kuruc, J D -- Crooks, A M -- Parker, D C -- Anderson, E M -- Kearney, M F -- Strain, M C -- Richman, D D -- Hudgens, M G -- Bosch, R J -- Coffin, J M -- Eron, J J -- Hazuda, D J -- Margolis, D M -- AI084553/AI/NIAID NIH HHS/ -- AI095052/AI/NIAID NIH HHS/ -- AI096113/AI/NIAID NIH HHS/ -- AI50410/AI/NIAID NIH HHS/ -- P30 AI050410/AI/NIAID NIH HHS/ -- R34 AI084553/AI/NIAID NIH HHS/ -- RR024383/RR/NCRR NIH HHS/ -- U01 AI095052/AI/NIAID NIH HHS/ -- U19 AI096113/AI/NIAID NIH HHS/ -- UL1 RR025747/RR/NCRR NIH HHS/ -- England -- Nature. 2012 Jul 25;487(7408):482-5. doi: 10.1038/nature11286.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22837004" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation/drug effects ; Anti-HIV Agents/*therapeutic use ; Biomarkers/metabolism ; CD4-Positive T-Lymphocytes/cytology/drug effects/metabolism/virology ; Gene Expression Regulation, Viral/drug effects ; HIV Infections/blood/*drug therapy/*virology ; HIV-1/*drug effects/genetics/*growth & development ; Histone Deacetylase Inhibitors/administration & dosage/adverse ; effects/pharmacology ; Histones/drug effects/metabolism ; Humans ; Hydroxamic Acids/administration & dosage/adverse effects/*pharmacology ; Proviruses/drug effects/genetics/growth & development ; RNA, Viral/biosynthesis/blood ; Risk Assessment ; Up-Regulation/drug effects ; Viremia/drug therapy/virology ; Virus Latency/*drug effects
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 7
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    The challenge of finding a cure for HIV infection (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-03-07
    Description: Although combination therapy for HIV infection represents a triumph for modern medicine, chronic suppressive therapy is required to contain persistent infection in reservoirs such as latently infected CD4+ lymphocytes and cells of the macrophage-monocyte lineage. Despite its success, chronic suppressive therapy is limited by its cost, the requirement of lifelong adherence, and the unknown effects of long-term treatment. This review discusses our current understanding of suppressive antiretroviral therapy, the latent viral reservoir, and the needs for and challenges of attacking this reservoir to achieve a cure.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Richman, Douglas D -- Margolis, David M -- Delaney, Martin -- Greene, Warner C -- Hazuda, Daria -- Pomerantz, Roger J -- New York, N.Y. -- Science. 2009 Mar 6;323(5919):1304-7. doi: 10.1126/science.1165706.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉San Diego VA Healthcare System and University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0679, USA. drichman@ucsd.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19265012" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS Vaccines ; Animals ; Anti-HIV Agents/economics/*therapeutic use ; Antiretroviral Therapy, Highly Active/adverse effects/economics ; CD4-Positive T-Lymphocytes/virology ; Clinical Trials as Topic ; Drug Discovery ; HIV/*drug effects/physiology ; HIV Infections/*drug therapy/virology ; Humans ; Viremia/drug therapy ; Virus Latency/*drug effects ; Virus Replication/drug effects
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 8
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    Terawatt-scale photovoltaics: Trajectories and challenges (2017)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2017-04-15
    Keywords: Physics, Applied, Economics, Engineering
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 9
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    The scientist's summer reading list (2019)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2019
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 10
    Electronic Resource
    Electronic Resource
    Specific inhibition of human leukocyte elastase by substituted alpha-pyrones (1984)
    Springer
    Cellular and molecular life sciences 40 (1984), S. 361-362 
    Details
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Severala-pyrones have been synthesized and investigated for their in vitro inhibitory activity usinga-chymotrypsin (a-CT), porcine pancreatic elastase, (PPE) and human leukocyte elastase (HLE). 4-Hydroxy-6-undecyl-2H-pyran-2-one4, 4-Hydroxy-6-[(1-butyl)heptyl]-2H-pyran-2-one5 and 4-Methoxy-6-[(1-butyl)heptyl]-2H-pyran-2-one6 were found to be specific inhibitors of HLE. These compounds constitute a promising new class of HLE inhibitors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01952552
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    Paper (German National Licenses)
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