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  • 1
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    GWAS of HIV-1 control [Genetics] (2015)
    National Academy of Sciences
    Details
    Publication Date: 2015-11-25
    Description: Previous genome-wide association studies (GWAS) of HIV-1–infected populations have been underpowered to detect common variants with moderate impact on disease outcome and have not assessed the phenotypic variance explained by genome-wide additive effects. By combining the majority of available genome-wide genotyping data in HIV-infected populations, we tested for association between...
    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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  • 2
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    Spatial patterns in zooplankton communities across the eastern Canadian sub-Arctic and Arctic waters: insights from stable carbon ({delta}13C) and nitrogen ({delta}15N) isotope ratios (2011)
    Oxford University Press
    Details
    Publication Date: 2011-11-24
    Description: This study defined the status quo of biogeographic domains and examined spatial patterns of stable isotopes (SIs) of carbon and nitrogen in relation to biophysical groupings to gain greater insight into how mesozooplankton may respond to continuous environmental change in the Canadian Arctic and sub-Arctic regions. Mesozooplankton communities were sampled during the summer of 2007 along a transect from Belle-Isle Strait, NFL, to Kugluktuk, NU (Canada), and during the early autumn of 2009 along a transect extending from Pelly Bay to Hall Beach, NU. Five broad water mass types corresponded to geographical regions. In general, we found relationships between water mass and species composition; however, this relationship was not always straightforward. Mesozooplankton community composition varied along the transect, revealing eight species assemblages. Calanus finmarchicus was abundant in the warmer and saltier Atlantic waters of the Labrador Sea, whereas Calanus hyperboreus , Calanus glacialis and Metridia longa were most abundant in the cold Arctic waters of Central Baffin Bay and in the eastern portion of the Canadian Arctic Archipelago. Nitrogen and carbon SI analysis revealed that 15 N (but not 13 C) varied spatially for C. glacialis , C. hyperboreus , Paraeuchaeta spp. and Themisto libellula . 15 N values were less enriched in Davis Strait and more enriched in the Gulf of Boothia. Seasonality, oceanic fronts and changes in the trophic structure at the base of each regional food web may explain some of the observed variability. This study represents the first broad-scale characterization of the composition and isotopic signatures for mesozooplankton communities ranging from the sub-Arctic Atlantic to the western Central Arctic Archipelago. Our study provides a baseline of the zooplankton community for monitoring species biogeographical range.
    Print ISSN: 0142-7873
    Electronic ISSN: 1464-3774
    Topics: Biology
    Published by Oxford University Press
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  • 3
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    Spin-dependent two-electron emission from ferromagnetic Fe(001) (2011)
    American Physical Society (APS)
    Details
    Publication Date: 2011-10-12
    Description: Author(s): F. Giebels, H. Gollisch, R. Feder, F. O. Schumann, C. Winkler, and J. Kirschner [Phys. Rev. B 84, 165421] Published Tue Oct 11, 2011
    Keywords: Surface physics, nanoscale physics, low-dimensional systems
    Print ISSN: 1098-0121
    Electronic ISSN: 1095-3795
    Topics: Physics
    Published by American Physical Society (APS)
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  • 4
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    Genetic acceleration of AIDS progression by a promoter variant of CCR5 (1998)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1998-12-04
    Description: The CCR5 gene encodes a cell surface chemokine receptor molecule that serves as the principal coreceptor, with CD4, for macrophage-tropic (R5) strains of human immunodeficiency virus-type 1 (HIV-1). Genetic association analysis of five cohorts of people with acquired immunodeficiency syndrome (AIDS) revealed that infected individuals homozygous for a multisite haplotype of the CCR5 regulatory region containing the promoter allele, CCR5P1, progress to AIDS more rapidly than those with other CCR5 promoter genotypes, particularly in the early years after infection. Composite genetic epidemiologic analyses of genotypes bearing CCR5P1, CCR5-Delta32, CCR2-64I, and SDF1-3'A affirmed distinct regulatory influences for each gene on AIDS progression. An estimated 10 to 17 percent of patients who develop AIDS within 3.5 years of HIV-1 infection do so because they are homozygous for CCR5P1/P1, and 7 to 13 percent of all people carry this susceptible genotype. The cumulative and interactive influence of these AIDS restriction genes illustrates the multigenic nature of host factors limiting AIDS disease progression.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Martin, M P -- Dean, M -- Smith, M W -- Winkler, C -- Gerrard, B -- Michael, N L -- Lee, B -- Doms, R W -- Margolick, J -- Buchbinder, S -- Goedert, J J -- O'Brien, T R -- Hilgartner, M W -- Vlahov, D -- O'Brien, S J -- Carrington, M -- N01-CO-56000/CO/NCI NIH HHS/ -- New York, N.Y. -- Science. 1998 Dec 4;282(5395):1907-11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Science Applications International Corporation (SAIC), National Cancer Institute, Frederick MD 21702, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9836644" target="_blank"〉PubMed〈/a〉
    Keywords: Acquired Immunodeficiency Syndrome/genetics/mortality/*physiopathology ; Alleles ; Chemokine CXCL12 ; Chemokines, CXC/genetics ; Cohort Studies ; Disease Progression ; Genes, Dominant ; Genes, Recessive ; Genetic Predisposition to Disease ; Genotype ; HIV Infections/genetics/physiopathology ; *Hiv-1 ; Haplotypes ; Heterozygote ; Homozygote ; Humans ; *Promoter Regions, Genetic ; Proportional Hazards Models ; Receptors, CCR2 ; Receptors, CCR5/*genetics ; *Receptors, Chemokine ; Receptors, Cytokine/*genetics ; Risk Factors ; Survival Rate
    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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    An asymmetric distribution of positrons in the Galactic disk revealed by gamma-rays (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-01-11
    Description: Gamma-ray line radiation at 511 keV is the signature of electron-positron annihilation. Such radiation has been known for 30 years to come from the general direction of the Galactic Centre, but the origin of the positrons has remained a mystery. Stellar nucleosynthesis, accreting compact objects, and even the annihilation of exotic dark-matter particles have all been suggested. Here we report a distinct asymmetry in the 511-keV line emission coming from the inner Galactic disk ( approximately 10-50 degrees from the Galactic Centre). This asymmetry resembles an asymmetry in the distribution of low mass X-ray binaries with strong emission at photon energies 〉20 keV ('hard' LMXBs), indicating that they may be the dominant origin of the positrons. Although it had long been suspected that electron-positron pair plasmas may exist in X-ray binaries, it was not evident that many of the positrons could escape to lose energy and ultimately annihilate with electrons in the interstellar medium and thus lead to the emission of a narrow 511-keV line. For these models, our result implies that up to a few times 10(41) positrons escape per second from a typical hard LMXB. Positron production at this level from hard LMXBs in the Galactic bulge would reduce (and possibly eliminate) the need for more exotic explanations, such as those involving dark matter.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Weidenspointner, Georg -- Skinner, Gerry -- Jean, Pierre -- Knodlseder, Jurgen -- von Ballmoos, Peter -- Bignami, Giovanni -- Diehl, Roland -- Strong, Andrew W -- Cordier, Bertrand -- Schanne, Stephane -- Winkler, Christoph -- England -- Nature. 2008 Jan 10;451(7175):159-62. doi: 10.1038/nature06490.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre d'Etude Spatiale des Rayonnements, CNRS/UPS, BP 44346, Toulouse Cedex 4, France. Georg.Weidenspointner@hll.mpg.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18185581" target="_blank"〉PubMed〈/a〉
    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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  • 6
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    Riboswitches. A riboswitch-containing sRNA controls gene expression by sequestration of a response regulator (2014)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2014-08-26
    Description: The ethanolamine utilization (eut) locus of Enterococcus faecalis, containing at least 19 genes distributed over four polycistronic messenger RNAs, appears to be regulated by a single adenosyl cobalamine (AdoCbl)-responsive riboswitch. We report that the AdoCbl-binding riboswitch is part of a small, trans-acting RNA, EutX, which additionally contains a dual-hairpin substrate for the RNA binding-response regulator, EutV. In the absence of AdoCbl, EutX uses this structure to sequester EutV. EutV is known to regulate the eut messenger RNAs by binding dual-hairpin structures that overlap terminators and thus prevent transcription termination. In the presence of AdoCbl, EutV cannot bind to EutX and, instead, causes transcriptional read through of multiple eut genes. This work introduces riboswitch-mediated control of protein sequestration as a posttranscriptional mechanism to coordinately regulate gene expression.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356242/" 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/PMC4356242/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉DebRoy, Sruti -- Gebbie, Margo -- Ramesh, Arati -- Goodson, Jonathan R -- Cruz, Melissa R -- van Hoof, Ambro -- Winkler, Wade C -- Garsin, Danielle A -- P30 DK056338/DK/NIDDK NIH HHS/ -- R01 AI076406/AI/NIAID NIH HHS/ -- R01 AI110432/AI/NIAID NIH HHS/ -- R01 GM099790/GM/NIGMS NIH HHS/ -- R01AI076406/AI/NIAID NIH HHS/ -- R01GM099790/GM/NIGMS NIH HHS/ -- R56 AI110432/AI/NIAID NIH HHS/ -- R56AI110432/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2014 Aug 22;345(6199):937-40. doi: 10.1126/science.1255091.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Molecular Genetics, The University of Texas Health Science Center at Houston, TX 77030, USA. ; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA. ; Department of Biochemistry, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. ; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA. danielle.a.garsin@uth.tmc.edu wwinkler@umd.edu. ; Department of Microbiology and Molecular Genetics, The University of Texas Health Science Center at Houston, TX 77030, USA. danielle.a.garsin@uth.tmc.edu wwinkler@umd.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25146291" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Cobamides/*metabolism ; Enterococcus faecalis/*genetics/metabolism ; Ethanolamine/*metabolism ; *Gene Expression Regulation, Bacterial ; Molecular Sequence Data ; Nucleic Acid Conformation ; RNA, Messenger/chemistry/genetics/*metabolism ; *Response Elements ; Riboswitch/genetics/*physiology ; *Transcription, Genetic
    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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  • 7
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    Contrasting genetic influence of CCR2 and CCR5 variants on HIV-1 infection and disease progression. Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC), ALIVE Study (1997)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1997-08-15
    Description: The critical role of chemokine receptors (CCR5 and CXCR4) in human immunodeficiency virus-type 1 (HIV-1) infection and pathogenesis prompted a search for polymorphisms in other chemokine receptor genes that mediate HIV-1 disease progression. A mutation (CCR2-64I) within the first transmembrane region of the CCR2 chemokine and HIV-1 receptor gene is described that occurred at an allele frequency of 10 to 15 percent among Caucasians and African Americans. Genetic association analysis of five acquired immunodeficiency syndrome (AIDS) cohorts (3003 patients) revealed that although CCR2-64I exerts no influence on the incidence of HIV-1 infection, HIV-1-infected individuals carrying the CCR2-64I allele progressed to AIDS 2 to 4 years later than individuals homozygous for the common allele. Because CCR2-64I occurs invariably on a CCR5-+-bearing chromosomal haplotype, the independent effects of CCR5-Delta32 (which also delays AIDS onset) and CCR2-64I were determined. An estimated 38 to 45 percent of AIDS patients whose disease progresses rapidly (less than 3 years until onset of AIDS symptoms after HIV-1 exposure) can be attributed to their CCR2-+/+ or CCR5-+/+ genotype, whereas the survival of 28 to 29 percent of long-term survivors, who avoid AIDS for 16 years or more, can be explained by a mutant genotype for CCR2 or CCR5.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Smith, M W -- Dean, M -- Carrington, M -- Winkler, C -- Huttley, G A -- Lomb, D A -- Goedert, J J -- O'Brien, T R -- Jacobson, L P -- Kaslow, R -- Buchbinder, S -- Vittinghoff, E -- Vlahov, D -- Hoots, K -- Hilgartner, M W -- O'Brien, S J -- New York, N.Y. -- Science. 1997 Aug 15;277(5328):959-65.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Science Applications International Corp. Frederick, National Cancer Institute, Frederick, MD 21702-1201, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9252328" target="_blank"〉PubMed〈/a〉
    Keywords: Acquired Immunodeficiency Syndrome/*genetics/immunology/mortality/virology ; African Continental Ancestry Group ; Cohort Studies ; Disease Progression ; European Continental Ancestry Group ; Genotype ; HIV Infections/*genetics/immunology/mortality/virology ; *Hiv-1 ; Haplotypes ; Heterozygote ; Humans ; *Mutation ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single-Stranded Conformational ; Proportional Hazards Models ; Receptors, CCR2 ; Receptors, CCR5 ; *Receptors, Chemokine ; Receptors, Cytokine/*genetics ; Receptors, HIV/*genetics ; Survival Analysis
    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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  • 8
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    Three-dimensional structure of herpes simplex virus from cryo-electron tomography (2003)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2003-11-25
    Description: Herpes simplex virus, a DNA virus of high complexity, consists of a nucleocapsid surrounded by the tegument-a protein compartment-and the envelope. The latter components, essential for infectivity, are pleiomorphic. Visualized in cryo-electron tomograms of isolated virions, the tegument was seen to form an asymmetric cap: On one side, the capsid closely approached the envelope; on the other side, they were separated by approximately 35 nanometers of tegument. The tegument substructure was particulate, with some short actin-like filaments. The envelope contained 600 to 750 glycoprotein spikes that varied in length, spacing, and in the angles at which they emerge from the membrane. Their distribution was nonrandom, suggesting functional clustering.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grunewald, Kay -- Desai, Prashant -- Winkler, Dennis C -- Heymann, J Bernard -- Belnap, David M -- Baumeister, Wolfgang -- Steven, Alasdair C -- AI33077/AI/NIAID NIH HHS/ -- R01 AI033077/AI/NIAID NIH HHS/ -- R01 AI033077-10/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2003 Nov 21;302(5649):1396-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Structural Biology, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14631040" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Capsid/chemistry/ultrastructure ; Cercopithecus aethiops ; Cryoelectron Microscopy ; Herpesvirus 1, Human/*chemistry/physiology/*ultrastructure ; Humans ; Image Processing, Computer-Assisted ; Lipid Bilayers ; Nucleocapsid/ultrastructure ; Tomography ; Vero Cells ; Viral Envelope Proteins/analysis/ultrastructure ; Virion/ultrastructure
    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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  • 9
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    Tuberous sclerosis complex is required for tumor maintenance in MYC-driven Burkitt's lymphoma (2018)
    Springer Nature
    Details
    Publication Date: 2018
    Description: 〈p〉The tuberous sclerosis complex (TSC) 1/2 is a negative regulator of the nutrient-sensing kinase mechanistic target of rapamycin complex (mTORC1), and its function is generally associated with tumor suppression. Nevertheless, biallelic loss of function of TSC1 or TSC2 is rarely found in malignant tumors. Here, we show that TSC1/2 is highly expressed in Burkitt's lymphoma cell lines and patient samples of human Burkitt's lymphoma, a prototypical MYC-driven cancer. Mechanistically, we show that MYC induces TSC1 expression by transcriptional activation of the TSC1 promoter and repression of miR-15a. TSC1 knockdown results in elevated mTORC1-dependent mitochondrial respiration enhanced ROS production and apoptosis. Moreover, TSC1 deficiency attenuates tumor growth in a xenograft mouse model. Our study reveals a novel role for TSC1 in securing homeostasis between MYC and mTORC1 that is required for cell survival and tumor maintenance in Burkitt's lymphoma. The study identifies TSC1/2 inhibition and/or mTORC1 hyperactivation as a novel therapeutic strategy for MYC-driven cancers.〈/p〉
    Print ISSN: 0261-4189
    Electronic ISSN: 1460-2075
    Topics: Biology , Medicine
    Published by Springer Nature on behalf of The European Molecular Biology Organization (EMBO).
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  • 10
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    Genetic restriction of AIDS pathogenesis by an SDF-1 chemokine gene variant. ALIVE Study, Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC) (1998)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1998-02-07
    Description: Stromal-derived factor (SDF-1) is the principal ligand for CXCR4, a coreceptor with CD4 for T lymphocyte cell line-tropic human immunodeficiency virus-type 1 (HIV-1). A common polymorphism, SDF1-3'A, was identified in an evolutionarily conserved segment of the 3' untranslated region of the SDF-1 structural gene transcript. In the homozygous state, SDF1-3'A/3'A delays the onset of acquired immunodeficiency syndrome (AIDS), according to a genetic association analysis of 2857 patients enrolled in five AIDS cohort studies. The recessive protective effect of SDF1-3'A was increasingly pronounced in individuals infected with HIV-1 for longer periods, was twice as strong as the dominant genetic restriction of AIDS conferred by CCR5 and CCR2 chemokine receptor variants in these populations, and was complementary with these mutations in delaying the onset of AIDS.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Winkler, C -- Modi, W -- Smith, M W -- Nelson, G W -- Wu, X -- Carrington, M -- Dean, M -- Honjo, T -- Tashiro, K -- Yabe, D -- Buchbinder, S -- Vittinghoff, E -- Goedert, J J -- O'Brien, T R -- Jacobson, L P -- Detels, R -- Donfield, S -- Willoughby, A -- Gomperts, E -- Vlahov, D -- Phair, J -- O'Brien, S J -- New York, N.Y. -- Science. 1998 Jan 16;279(5349):389-93.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Science Applications International Corporation (SAIC), National Cancer Institute, Frederick, MD 21702, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9430590" target="_blank"〉PubMed〈/a〉
    Keywords: Acquired Immunodeficiency Syndrome/genetics/*immunology/virology ; Adult ; Chemokine CXCL12 ; Chemokines/chemistry/*genetics/physiology ; *Chemokines, CXC ; Cohort Studies ; Continental Population Groups ; Disease Progression ; Genes ; Genetic Variation ; Genotype ; HIV Infections/genetics/*immunology/virology ; HIV-1/*physiology ; Heterozygote ; Humans ; Male ; Molecular Sequence Data ; Odds Ratio ; Polymorphism, Genetic ; Receptors, CCR2 ; Receptors, CCR5/genetics/physiology ; Receptors, CXCR4/metabolism ; Receptors, Chemokine/genetics/physiology ; Survival Analysis ; T-Lymphocytes/virology
    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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