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  • 1
    Publication Date: 2012-02-22
    Description: Trimethylation of histone H3 on lysine 27 (H3K27me3) is a repressive posttranslational modification mediated by the histone methyltransferase EZH2. EZH2 is a component of the polycomb repressive complex 2 and is overexpressed in many cancers. In B-cell lymphomas, its substrate preference is frequently altered through somatic mutation of the EZH2 Y641 residue. Herein, we identify mutation of EZH2 A677 to a glycine (A677G) among lymphoma cell lines and primary tumor specimens. Similar to Y641 mutant cell lines, an A677G mutant cell line revealed aberrantly elevated H3K27me3 and decreased monomethylated H3K27 (H3K27me1) and dimethylated H3K27 (H3K27me2). A677G EZH2 possessed catalytic activity with a substrate specificity that was distinct from those of both WT EZH2 and Y641 mutants. Whereas WT EZH2 displayed a preference for substrates with less methylation [unmethylated H3K27 (H3K27me0):me1:me2 kcat/Km ratio = 9:6:1] and Y641 mutants preferred substrates with greater methylation (H3K27me0:me1:me2 kcat/Km ratio = 1:2:13), the A677G EZH2 demonstrated nearly equal efficiency for all three substrates (H3K27me0:me1:me2 kcat/Km ratio = 1.1:0.6:1). When transiently expressed in cells, A677G EZH2, but not WT EZH2, increased global H3K27me3 and decreased H3K27me2. Structural modeling of WT and mutant EZH2 suggested that the A677G mutation acquires the ability to methylate H3K27me2 through enlargement of the lysine tunnel while preserving activity with H3K27me0/me1 substrates through retention of the Y641 residue that is crucial for orientation of these smaller substrates. This mutation highlights the interplay between Y641 and A677 residues in the substrate specificity of EZH2 and identifies another lymphoma patient population that harbors an activating mutation of EZH2.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 2
    Publication Date: 2012-07-11
    Description: Author(s): Max C. Watson, Erik G. Brandt, Paul M. Welch, and Frank L. H. Brown Thermal fluctuations of lipid orientation are analyzed to infer the bending rigidity of lipid bilayers directly from molecular simulations. Compared to the traditional analysis of thermal membrane undulations, the proposed method is reliable down to shorter wavelengths and allows for determination o... [Phys. Rev. Lett. 109, 028102] Published Tue Jul 10, 2012
    Keywords: Soft Matter, Biological, and Interdisciplinary Physics
    Print ISSN: 0031-9007
    Electronic ISSN: 1079-7114
    Topics: Physics
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  • 3
    Publication Date: 2015-03-04
    Description: We generated genome-wide data from 69 Europeans who lived between 8,000-3,000 years ago by enriching ancient DNA libraries for a target set of almost 400,000 polymorphisms. Enrichment of these positions decreases the sequencing required for genome-wide ancient DNA analysis by a median of around 250-fold, allowing us to study an order of magnitude more individuals than previous studies and to obtain new insights about the past. We show that the populations of Western and Far Eastern Europe followed opposite trajectories between 8,000-5,000 years ago. At the beginning of the Neolithic period in Europe, approximately 8,000-7,000 years ago, closely related groups of early farmers appeared in Germany, Hungary and Spain, different from indigenous hunter-gatherers, whereas Russia was inhabited by a distinctive population of hunter-gatherers with high affinity to a approximately 24,000-year-old Siberian. By approximately 6,000-5,000 years ago, farmers throughout much of Europe had more hunter-gatherer ancestry than their predecessors, but in Russia, the Yamnaya steppe herders of this time were descended not only from the preceding eastern European hunter-gatherers, but also from a population of Near Eastern ancestry. Western and Eastern Europe came into contact approximately 4,500 years ago, as the Late Neolithic Corded Ware people from Germany traced approximately 75% of their ancestry to the Yamnaya, documenting a massive migration into the heartland of Europe from its eastern periphery. This steppe ancestry persisted in all sampled central Europeans until at least approximately 3,000 years ago, and is ubiquitous in present-day Europeans. These results provide support for a steppe origin of at least some of the Indo-European languages of Europe.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Haak, Wolfgang -- Lazaridis, Iosif -- Patterson, Nick -- Rohland, Nadin -- Mallick, Swapan -- Llamas, Bastien -- Brandt, Guido -- Nordenfelt, Susanne -- Harney, Eadaoin -- Stewardson, Kristin -- Fu, Qiaomei -- Mittnik, Alissa -- Banffy, Eszter -- Economou, Christos -- Francken, Michael -- Friederich, Susanne -- Pena, Rafael Garrido -- Hallgren, Fredrik -- Khartanovich, Valery -- Khokhlov, Aleksandr -- Kunst, Michael -- Kuznetsov, Pavel -- Meller, Harald -- Mochalov, Oleg -- Moiseyev, Vayacheslav -- Nicklisch, Nicole -- Pichler, Sandra L -- Risch, Roberto -- Rojo Guerra, Manuel A -- Roth, Christina -- Szecsenyi-Nagy, Anna -- Wahl, Joachim -- Meyer, Matthias -- Krause, Johannes -- Brown, Dorcas -- Anthony, David -- Cooper, Alan -- Alt, Kurt Werner -- Reich, David -- GM100233/GM/NIGMS NIH HHS/ -- R01 HG006399/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 Jun 11;522(7555):207-11. doi: 10.1038/nature14317. Epub 2015 Mar 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Australian Centre for Ancient DNA, School of Earth and Environmental Sciences &Environment Institute, University of Adelaide, Adelaide, South Australia 5005, Australia. ; 1] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA. ; Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA. ; 1] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA [3] Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115, USA. ; Institute of Anthropology, Johannes Gutenberg University of Mainz, D-55128 Mainz, Germany. ; 1] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA [3] Max Planck Institute for Evolutionary Anthropology, D-04103 Leipzig, Germany [4] Key Laboratory of Vertebrate Evolution and Human Origins of Chinese Academy of Sciences, IVPP, CAS, Beijing 100049, China. ; Institute for Archaeological Sciences, University of Tubingen, D-72070 Tubingen, Germany. ; 1] Institute of Archaeology, Research Centre for the Humanities, Hungarian Academy of Science, H-1014 Budapest, Hungary [2] Romisch Germanische Kommission (RGK) Frankfurt, D-60325 Frankfurt, Germany. ; Archaeological Research Laboratory, Stockholm University, 114 18 Stockholm, Sweden. ; Departments of Paleoanthropology and Archaeogenetics, Senckenberg Center for Human Evolution and Paleoenvironment, University of Tubingen, D-72070 Tubingen, Germany. ; State Office for Heritage Management and Archaeology Saxony-Anhalt and State Museum of Prehistory, D-06114 Halle, Germany. ; Departamento de Prehistoria y Arqueologia, Facultad de Filosofia y Letras, Universidad Autonoma de Madrid, E-28049 Madrid, Spain. ; The Cultural Heritage Foundation, Vasteras 722 12, Sweden. ; Peter the Great Museum of Anthropology and Ethnography (Kunstkamera) RAS, St Petersburg 199034, Russia. ; Volga State Academy of Social Sciences and Humanities, Samara 443099, Russia. ; Deutsches Archaeologisches Institut, Abteilung Madrid, E-28002 Madrid, Spain. ; 1] Institute of Anthropology, Johannes Gutenberg University of Mainz, D-55128 Mainz, Germany [2] State Office for Heritage Management and Archaeology Saxony-Anhalt and State Museum of Prehistory, D-06114 Halle, Germany [3] Danube Private University, A-3500 Krems, Austria. ; Institute for Prehistory and Archaeological Science, University of Basel, CH-4003 Basel, Switzerland. ; Departamento de Prehistoria, Universitat Autonoma de Barcelona, E-08193 Barcelona, Spain. ; Departamento de Prehistoria y Arqueolgia, Universidad de Valladolid, E-47002 Valladolid, Spain. ; 1] Institute of Anthropology, Johannes Gutenberg University of Mainz, D-55128 Mainz, Germany [2] Institute of Archaeology, Research Centre for the Humanities, Hungarian Academy of Science, H-1014 Budapest, Hungary. ; State Office for Cultural Heritage Management Baden-Wurttemberg, Osteology, D-78467 Konstanz, Germany. ; Max Planck Institute for Evolutionary Anthropology, D-04103 Leipzig, Germany. ; 1] Institute for Archaeological Sciences, University of Tubingen, D-72070 Tubingen, Germany [2] Departments of Paleoanthropology and Archaeogenetics, Senckenberg Center for Human Evolution and Paleoenvironment, University of Tubingen, D-72070 Tubingen, Germany [3] Max Planck Institute for the Science of Human History, D-07745 Jena, Germany. ; Anthropology Department, Hartwick College, Oneonta, New York 13820, USA. ; 1] Institute of Anthropology, Johannes Gutenberg University of Mainz, D-55128 Mainz, Germany [2] State Office for Heritage Management and Archaeology Saxony-Anhalt and State Museum of Prehistory, D-06114 Halle, Germany [3] Danube Private University, A-3500 Krems, Austria [4] Institute for Prehistory and Archaeological Science, University of Basel, CH-4003 Basel, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25731166" target="_blank"〉PubMed〈/a〉
    Keywords: Cultural Evolution/*history ; Europe/ethnology ; Genome, Human/genetics ; *Grassland ; History, Ancient ; Human Migration/*history ; Humans ; Language/*history ; Male ; Polymorphism, Genetic/genetics ; Population Dynamics ; Russia
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2013-10-12
    Description: The processes that shaped modern European mitochondrial DNA (mtDNA) variation remain unclear. The initial peopling by Palaeolithic hunter-gatherers ~42,000 years ago and the immigration of Neolithic farmers into Europe ~8000 years ago appear to have played important roles but do not explain present-day mtDNA diversity. We generated mtDNA profiles of 364 individuals from prehistoric cultures in Central Europe to perform a chronological study, spanning the Early Neolithic to the Early Bronze Age (5500 to 1550 calibrated years before the common era). We used this transect through time to identify four marked shifts in genetic composition during the Neolithic period, revealing a key role for Late Neolithic cultures in shaping modern Central European genetic diversity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039305/" 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/PMC4039305/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brandt, Guido -- Haak, Wolfgang -- Adler, Christina J -- Roth, Christina -- Szecsenyi-Nagy, Anna -- Karimnia, Sarah -- Moller-Rieker, Sabine -- Meller, Harald -- Ganslmeier, Robert -- Friederich, Susanne -- Dresely, Veit -- Nicklisch, Nicole -- Pickrell, Joseph K -- Sirocko, Frank -- Reich, David -- Cooper, Alan -- Alt, Kurt W -- Genographic Consortium -- R01 GM100233/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Oct 11;342(6155):257-61. doi: 10.1126/science.1241844.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Anthropology, Johannes Gutenberg University of Mainz, Mainz, Germany. brandtg@uni-mainz.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24115443" target="_blank"〉PubMed〈/a〉
    Keywords: Agriculture/history ; Base Sequence ; DNA, Mitochondrial/*genetics/history ; Europe ; *Genetic Drift ; *Genetic Variation ; History, Ancient ; Humans ; Molecular Sequence Data ; Population/*genetics ; Transients and Migrants
    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: 2005-11-15
    Description: The ancestry of modern Europeans is a subject of debate among geneticists, archaeologists, and anthropologists. A crucial question is the extent to which Europeans are descended from the first European farmers in the Neolithic Age 7500 years ago or from Paleolithic hunter-gatherers who were present in Europe since 40,000 years ago. Here we present an analysis of ancient DNA from early European farmers. We successfully extracted and sequenced intact stretches of maternally inherited mitochondrial DNA (mtDNA) from 24 out of 57 Neolithic skeletons from various locations in Germany, Austria, and Hungary. We found that 25% of the Neolithic farmers had one characteristic mtDNA type and that this type formerly was widespread among Neolithic farmers in Central Europe. Europeans today have a 150-times lower frequency (0.2%) of this mtDNA type, revealing that these first Neolithic farmers did not have a strong genetic influence on modern European female lineages. Our finding lends weight to a proposed Paleolithic ancestry for modern Europeans.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Haak, Wolfgang -- Forster, Peter -- Bramanti, Barbara -- Matsumura, Shuichi -- Brandt, Guido -- Tanzer, Marc -- Villems, Richard -- Renfrew, Colin -- Gronenborn, Detlef -- Alt, Kurt Werner -- Burger, Joachim -- New York, N.Y. -- Science. 2005 Nov 11;310(5750):1016-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut fur Anthropologie, Johannes Gutenberg Universitat Mainz, Saarstrasse 21, D-55099 Mainz, Germany. haakw@uni-mainz.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16284177" target="_blank"〉PubMed〈/a〉
    Keywords: Agriculture/*history ; Austria ; Base Sequence ; Computer Simulation ; Cultural Evolution ; DNA, Mitochondrial/chemistry/classification/*genetics/history ; Emigration and Immigration ; Europe ; European Continental Ancestry Group/*genetics/history ; Female ; Gene Frequency ; Genetic Drift ; Genetics, Population ; Germany ; Haplotypes ; History, Ancient ; Humans ; Hungary ; Male ; Molecular Sequence Data ; Population Dynamics
    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: 2019
    Description: 〈div data-abstract-type="normal"〉〈p〉We present a study of Lagrangian intermittency and its characteristic time scales. Using the concepts of flying and diving residence times above and below a given threshold in the magnitude of turbulence quantities, we infer the time spectra of the Lagrangian temporal fluctuations of dissipation, acceleration and enstrophy by means of a direct numerical simulation in homogeneous and isotropic turbulence. We then relate these time scales, first, to the presence of extreme events in turbulence and, second, to the local flow characteristics. Analyses confirm the existence in turbulent quantities of holes mirroring bursts, both of which are at the core of what constitutes Lagrangian intermittency. It is shown that holes are associated with quiescent laminar regions of the flow. Moreover, Lagrangian holes occur over few Kolmogorov time scales while Lagrangian bursts happen over longer periods scaling with the global decorrelation time scale, hence showing that loss of the history of the turbulence quantities along particle trajectories in turbulence is not continuous. Such a characteristic partially explains why current Lagrangian stochastic models fail at reproducing our results. More generally, the Lagrangian dataset of residence times shown here represents another manner for qualifying the accuracy of models. We also deliver a theoretical approximation of mean residence times, which highlights the importance of the correlation between turbulence quantities and their time derivatives in setting temporal statistics. Finally, whether in a hole or a burst, the straining structure along particle trajectories always evolves self-similarly (in a statistical sense) from shearless two-dimensional to shear bi-axial configurations. We speculate that this latter configuration represents the optimum manner to dissipate locally the available energy.〈/p〉〈/div〉
    Print ISSN: 0022-1120
    Electronic ISSN: 1469-7645
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
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  • 7
    Publication Date: 2013-07-13
    Description: Author(s): Erik G. Brandt The stochastic Eulerian-Lagrangian method (SELM) is used to simulate coarse-grained lipid membrane models under steady-state conditions and in shear flow. SELM is an immersed boundary method which combines the efficiency of particle-based simulations with the realistic solvent dynamics provided by f... [Phys. Rev. E 88, 012714] Published Fri Jul 12, 2013
    Keywords: Biological Physics
    Print ISSN: 1539-3755
    Electronic ISSN: 1550-2376
    Topics: Physics
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  • 8
    Publication Date: 2013-03-13
    Description: Isoprenyl diphosphate synthases (IDSs) produce the ubiquitous branched-chain diphosphates of different lengths that are precursors of all major classes of terpenes. Typically, individual short-chain IDSs (scIDSs) make the C10, C15, and C20 isoprenyl diphosphates separately. Here, we report that the product length synthesized by a single scIDS shifts depending on...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 9
    Publication Date: 2018-03-06
    Description: Previous studies suggest that the growth of supermassive black holes (SMBHs) may be fundamentally related to host-galaxy stellar mass ( M ⋆ ). To investigate this SMBH growth– M ⋆ relation in detail, we calculate long-term SMBH accretion rate as a function of M ⋆ and redshift [$\overline{\rm BHAR}(M_{\star }, z)$] over ranges of log ( M ⋆ /M ⊙ ) = 9.5–12 and z  = 0.4–4. Our $\overline{\rm BHAR}(M_{\star }, z)$ is constrained by high-quality survey data (GOODS-South, GOODS-North and COSMOS), and by the stellar mass function and the X-ray luminosity function. At a given M ⋆ , $\overline{\rm BHAR}$ is higher at high redshift. This redshift dependence is stronger in more massive systems [for log ( M ⋆ /M ⊙ ) ≈ 11.5, $\overline{\rm BHAR}$ is three decades higher at z  = 4 than at z  = 0.5], possibly due to AGN feedback. Our results indicate that the ratio between $\overline{\rm BHAR}$ and average star formation rate ($\overline{\rm SFR}$) rises towards high M ⋆ at a given redshift. This $\overline{\rm BHAR}/\overline{\rm SFR}$ dependence on M ⋆ does not support the scenario that SMBH and galaxy growth are in lockstep. We calculate SMBH mass history [ M BH ( z )] based on our $\overline{\rm BHAR}(M_{\star }, z)$ and the M ⋆ ( z ) from the literature, and find that the M BH – M ⋆ relation has weak redshift evolution since z ≈ 2. The M BH / M ⋆ ratio is higher towards massive galaxies: it rises from ≈1/5000 at log  M ⋆ ≲ 10.5 to ≈1/500 at log  M ⋆ ≳ 11.2. Our predicted M BH / M ⋆ ratio at high M ⋆ is similar to that observed in local giant ellipticals, suggesting that SMBH growth from mergers is unlikely to dominate over growth from accretion.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
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  • 10
    Electronic Resource
    Electronic Resource
    Bradford : Emerald
    Industrial lubrication & tribology 52 (2000), S. 165-173 
    ISSN: 0036-8792
    Source: Emerald Fulltext Archive Database 1994-2005
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: The paper discusses the setup of a light duty axle efficiency test in evaluating gear lubricants for their fuel economy performance. Data collected with an internal reference oil highlight the repeatability of the test in different axles. Comparisons between single grade SAE 90 to multigrade gear lubricants were made under a variety of pinion torques and speeds to simulate highway and city driving conditions. A discussion of lubricant rheology and its importance to maintaining film strength for adequate bearing and gear lubrication for optimum torque efficiency and axle temperature is provided.
    Type of Medium: Electronic Resource
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