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  • 1
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    Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine (2011)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2011-05-13
    Description: The acquired immunodeficiency syndrome (AIDS)-causing lentiviruses human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) effectively evade host immunity and, once established, infections with these viruses are only rarely controlled by immunological mechanisms. However, the initial establishment of infection in the first few days after mucosal exposure, before viral dissemination and massive replication, may be more vulnerable to immune control. Here we report that SIV vaccines that include rhesus cytomegalovirus (RhCMV) vectors establish indefinitely persistent, high-frequency, SIV-specific effector memory T-cell (T(EM)) responses at potential sites of SIV replication in rhesus macaques and stringently control highly pathogenic SIV(MAC239) infection early after mucosal challenge. Thirteen of twenty-four rhesus macaques receiving either RhCMV vectors alone or RhCMV vectors followed by adenovirus 5 (Ad5) vectors (versus 0 of 9 DNA/Ad5-vaccinated rhesus macaques) manifested early complete control of SIV (undetectable plasma virus), and in twelve of these thirteen animals we observed long-term (〉/=1 year) protection. This was characterized by: occasional blips of plasma viraemia that ultimately waned; predominantly undetectable cell-associated viral load in blood and lymph node mononuclear cells; no depletion of effector-site CD4(+) memory T cells; no induction or boosting of SIV Env-specific antibodies; and induction and then loss of T-cell responses to an SIV protein (Vif) not included in the RhCMV vectors. Protection correlated with the magnitude of the peak SIV-specific CD8(+) T-cell responses in the vaccine phase, and occurred without anamnestic T-cell responses. Remarkably, long-term RhCMV vector-associated SIV control was insensitive to either CD8(+) or CD4(+) lymphocyte depletion and, at necropsy, cell-associated SIV was only occasionally measurable at the limit of detection with ultrasensitive assays, observations that indicate the possibility of eventual viral clearance. Thus, persistent vectors such as CMV and their associated T(EM) responses might significantly contribute to an efficacious HIV/AIDS vaccine.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3102768/" 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/PMC3102768/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hansen, Scott G -- Ford, Julia C -- Lewis, Matthew S -- Ventura, Abigail B -- Hughes, Colette M -- Coyne-Johnson, Lia -- Whizin, Nathan -- Oswald, Kelli -- Shoemaker, Rebecca -- Swanson, Tonya -- Legasse, Alfred W -- Chiuchiolo, Maria J -- Parks, Christopher L -- Axthelm, Michael K -- Nelson, Jay A -- Jarvis, Michael A -- Piatak, Michael Jr -- Lifson, Jeffrey D -- Picker, Louis J -- HHSN261200800001E/PHS HHS/ -- HHSN272200900037C/PHS HHS/ -- P51 RR00163/RR/NCRR NIH HHS/ -- R01 AI060392/AI/NIAID NIH HHS/ -- R01 AI060392-05/AI/NIAID NIH HHS/ -- R24 RR016001/RR/NCRR NIH HHS/ -- R56 AI060392/AI/NIAID NIH HHS/ -- R56 AI060392-06/AI/NIAID NIH HHS/ -- U24 OD010850/OD/NIH HHS/ -- England -- Nature. 2011 May 26;473(7348):523-7. doi: 10.1038/nature10003. Epub 2011 May 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vaccine and Gene Therapy Institute, Department of Molecular Microbiology, Oregon Health & Science University, Beaverton, Oregon 97006, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21562493" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS Vaccines/immunology ; Animals ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; Cytomegalovirus/genetics ; DNA, Viral/analysis ; Genetic Vectors/genetics ; Immunity, Mucosal/immunology ; Immunologic Memory/*immunology ; Macaca mulatta/blood/immunology/virology ; Male ; RNA, Viral/analysis ; SAIDS Vaccines/genetics/*immunology ; Simian Acquired Immunodeficiency Syndrome/blood/*immunology/*prevention & ; control/virology ; Simian Immunodeficiency Virus/growth & development/*immunology/isolation & ; purification/*pathogenicity ; T-Lymphocytes/*immunology ; Time Factors ; Vaccines, DNA/genetics/immunology ; Viral Load ; Virus Replication
    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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  • 2
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    Evasion of CD8+ T cells is critical for superinfection by cytomegalovirus (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-04-03
    Description: Cytomegalovirus (CMV) can superinfect persistently infected hosts despite CMV-specific humoral and cellular immunity; however, how it does so remains undefined. We have demonstrated that superinfection of rhesus CMV-infected rhesus macaques (RM) requires evasion of CD8+ T cell immunity by virally encoded inhibitors of major histocompatibility complex class I (MHC-I) antigen presentation, particularly the homologs of human CMV US2, 3, 6, and 11. In contrast, MHC-I interference was dispensable for primary infection of RM, or for the establishment of a persistent secondary infection in CMV-infected RM transiently depleted of CD8+ lymphocytes. These findings demonstrate that US2-11 glycoproteins promote evasion of CD8+ T cells in vivo, thus supporting viral replication and dissemination during superinfection, a process that complicates the development of preventive CMV vaccines but that can be exploited for CMV-based vector development.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2883175/" 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/PMC2883175/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hansen, Scott G -- Powers, Colin J -- Richards, Rebecca -- Ventura, Abigail B -- Ford, Julia C -- Siess, Don -- Axthelm, Michael K -- Nelson, Jay A -- Jarvis, Michael A -- Picker, Louis J -- Fruh, Klaus -- AI040101/AI/NIAID NIH HHS/ -- P51 RR000163/RR/NCRR NIH HHS/ -- P51 RR000163-460222/RR/NCRR NIH HHS/ -- P51 RR000163-486829/RR/NCRR NIH HHS/ -- P51 RR000163-496081/RR/NCRR NIH HHS/ -- P51 RR000163-508648/RR/NCRR NIH HHS/ -- R01 AI021640/AI/NIAID NIH HHS/ -- R01 AI021640-26/AI/NIAID NIH HHS/ -- R01 AI059457/AI/NIAID NIH HHS/ -- R01 AI059457-01A2/AI/NIAID NIH HHS/ -- R01 AI059457-02/AI/NIAID NIH HHS/ -- R01 AI059457-03/AI/NIAID NIH HHS/ -- R01 AI059457-04/AI/NIAID NIH HHS/ -- R01 AI059457-05/AI/NIAID NIH HHS/ -- R01 AI060392/AI/NIAID NIH HHS/ -- RR00163/RR/NCRR NIH HHS/ -- RR016001/RR/NCRR NIH HHS/ -- RR016025/RR/NCRR NIH HHS/ -- RR18107/RR/NCRR NIH HHS/ -- T32 AI007472/AI/NIAID NIH HHS/ -- T32 HL007781/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2010 Apr 2;328(5974):102-6. doi: 10.1126/science.1185350.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vaccine and Gene Therapy Institute, Oregon Health and Science University, 505 Northwest 185th Avenue, Beaverton, OR 97006, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20360110" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigen Presentation ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/*immunology ; Cytomegalovirus/genetics/immunology/*physiology ; Cytomegalovirus Infections/*immunology/*virology ; Cytomegalovirus Vaccines/immunology ; Disease Models, Animal ; Gene Products, gag/immunology ; Genes, Viral ; Histocompatibility Antigens Class I/immunology ; *Immune Evasion ; Immunologic Factors/genetics/*physiology ; Macaca mulatta ; Male ; Simian Immunodeficiency Virus/genetics/immunology ; Superinfection ; Viral Proteins/genetics/*physiology ; Virus Replication ; Virus Shedding
    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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  • 3
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    Coding potential of laboratory and clinical strains of human cytomegalovirus (2003)
    National Academy of Sciences
    Details
    Publication Date: 2003-12-01
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 4
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    The faint radio source population at 15.7 GHz - II. Multi-wavelength properties (2015)
    Oxford University Press
    Details
    Publication Date: 2015-09-27
    Description: A complete, flux density limited sample of 96 faint (〉0.5 mJy) radio sources is selected from the 10C survey at 15.7 GHz in the Lockman Hole. We have matched this sample to a range of multi-wavelength catalogues, including Spitzer Extragalactic Representative Volume Survey, Spitzer Wide-area Infrared Extragalactic survey, United Kingdom Infrared Telescope Infrared Deep Sky Survey and optical data; multi-wavelength counterparts are found for 80 of the 96 sources and spectroscopic redshifts are available for 24 sources. Photometric redshifts are estimated for the sources with multi-wavelength data available; the median redshift of the sample is 0.91 with an interquartile range of 0.84. Radio-to-optical ratios show that at least 94 per cent of the sample are radio loud, indicating that the 10C sample is dominated by radio galaxies. This is in contrast to samples selected at lower frequencies, where radio-quiet AGN and star-forming galaxies are present in significant numbers at these flux density levels. All six radio-quiet sources have rising radio spectra, suggesting that they are dominated by AGN emission. These results confirm the conclusions of Paper I that the faint, flat-spectrum sources which are found to dominate the 10C sample below ~1 mJy are the cores of radio galaxies. The properties of the 10C sample are compared to the Square Kilometre Array Design Studies Simulated Skies; a population of low-redshift star-forming galaxies predicted by the simulation is not found in the observed sample.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 5
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    Mechanism of APC/CCDC20 activation [Biochemistry] (2016)
    National Academy of Sciences
    Details
    Publication Date: 2016-05-12
    Description: Chromosome segregation and mitotic exit are initiated by the 1.2-MDa ubiquitin ligase APC/C (anaphase-promoting complex/cyclosome) and its coactivator CDC20 (cell division cycle 20). To avoid chromosome missegregation, APC/CCDC20 activation is tightly controlled. CDC20 only associates with APC/C in mitosis when APC/C has become phosphorylated and is further inhibited by a...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 6
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    A protein-based therapeutic for human cytomegalovirus infection (2000)
    National Academy of Sciences
    Details
    Publication Date: 2000-02-18
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 7
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    Chemokine-based toxin targeting the viral 7TM US28 [Microbiology] (2015)
    National Academy of Sciences
    Details
    Publication Date: 2015-07-08
    Description: The use of receptor–ligand interactions to direct toxins to kill diseased cells selectively has shown considerable promise for treatment of a number of cancers and, more recently, autoimmune disease. Here we move the fusion toxin protein (FTP) technology beyond cancer/autoimmune therapeutics to target the human viral pathogen, human cytomegalovirus (HCMV),...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 8
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    GPZ: non-stationary sparse Gaussian processes for heteroscedastic uncertainty estimation in photometric redshifts (2016)
    Oxford University Press
    Details
    Publication Date: 2016-08-07
    Description: The next generation of cosmology experiments will be required to use photometric redshifts rather than spectroscopic redshifts. Obtaining accurate and well-characterized photometric redshift distributions is therefore critical for Euclid , the Large Synoptic Survey Telescope and the Square Kilometre Array. However, determining accurate variance predictions alongside single point estimates is crucial, as they can be used to optimize the sample of galaxies for the specific experiment (e.g. weak lensing, baryon acoustic oscillations, supernovae), trading off between completeness and reliability in the galaxy sample. The various sources of uncertainty in measurements of the photometry and redshifts put a lower bound on the accuracy that any model can hope to achieve. The intrinsic uncertainty associated with estimates is often non-uniform and input-dependent, commonly known in statistics as heteroscedastic noise. However, existing approaches are susceptible to outliers and do not take into account variance induced by non-uniform data density and in most cases require manual tuning of many parameters. In this paper, we present a Bayesian machine learning approach that jointly optimizes the model with respect to both the predictive mean and variance we refer to as Gaussian processes for photometric redshifts (GP z ). The predictive variance of the model takes into account both the variance due to data density and photometric noise. Using the Sloan Digital Sky Survey (SDSS) DR12 data, we show that our approach substantially outperforms other machine learning methods for photo-z estimation and their associated variance, such as tpz and annz2 . We provide a matlab and python implementations that are available to download at https://github.com/OxfordML/GPz .
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 9
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    The faint radio source population at 15.7 GHz - II. Multi-wavelength properties (2015)
    Oxford University Press
    Details
    Publication Date: 2015-09-19
    Description: A complete, flux density limited sample of 96 faint (〉0.5 mJy) radio sources is selected from the 10C survey at 15.7 GHz in the Lockman Hole. We have matched this sample to a range of multi-wavelength catalogues, including Spitzer Extragalactic Representative Volume Survey, Spitzer Wide-area Infrared Extragalactic survey, United Kingdom Infrared Telescope Infrared Deep Sky Survey and optical data; multi-wavelength counterparts are found for 80 of the 96 sources and spectroscopic redshifts are available for 24 sources. Photometric redshifts are estimated for the sources with multi-wavelength data available; the median redshift of the sample is 0.91 with an interquartile range of 0.84. Radio-to-optical ratios show that at least 94 per cent of the sample are radio loud, indicating that the 10C sample is dominated by radio galaxies. This is in contrast to samples selected at lower frequencies, where radio-quiet AGN and star-forming galaxies are present in significant numbers at these flux density levels. All six radio-quiet sources have rising radio spectra, suggesting that they are dominated by AGN emission. These results confirm the conclusions of Paper I that the faint, flat-spectrum sources which are found to dominate the 10C sample below ~1 mJy are the cores of radio galaxies. The properties of the 10C sample are compared to the Square Kilometre Array Design Studies Simulated Skies; a population of low-redshift star-forming galaxies predicted by the simulation is not found in the observed sample.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 10
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    The link between accretion mode and environment in radio-loud active galaxies (2015)
    Oxford University Press
    Details
    Publication Date: 2015-09-27
    Description: The interactions between radio-loud AGN and their environments play an important rôle in galaxy and cluster evolution. Recent work has demonstrated fundamental differences between high- and low-excitation radio galaxies (HERGs and LERGs), and shown that they may have different relationships with their environments. In the Chandra Large Project ERA (Environments of Radio-loud AGN), we made the first systematic X-ray environmental study of the cluster environments of radio galaxies at a single epoch ( z  ~ 0.5), and found tentative evidence for a correlation between radio luminosity and cluster X-ray luminosity. We also found that this relationship appeared to be driven by the LERG subpopulation. We have now repeated the analysis with a low-redshift sample ( z  ~ 0.1), and found strong correlations between radio luminosity and environment richness and between radio luminosity and central density for the LERGs but not for the HERGs. These results are consistent with models in which the HERGs are fuelled from accretion discs maintained from local reservoirs of gas, while LERGs are fuelled more directly by gas ingested from the intracluster medium. Comparing the samples, we found that although the maximum environment richness of the HERG environments is similar in both samples, there are poorer HERG environments in the z  ~ 0.1 sample than in the z  ~ 0.5 sample. We have therefore tentative evidence of evolution of the HERG environments. We found no differences between the LERG subsamples for the two epochs, as would be expected if radio and cluster luminosities are related.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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