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  • 1
    Publication Date: 2013-12-07
    Description: Type II topoisomerases (Top2s) alter DNA topology via the formation of an enzyme–DNA adduct termed cleavage complex, which harbors a transient double-strand break in one DNA to allow the passage of another. Agents targeting human Top2s are clinically active anticancer drugs whose trapping of Top2-mediated DNA breakage effectively induces genome fragmentation and cell death. To understand the structural basis of this drug action, we previously determined the structure of human Top2 β-isoform forming a cleavage complex with the drug etoposide and DNA, and described the insertion of drug into DNA cleavage site and drug-induced decoupling of catalytic groups. By developing a post-crystallization drug replacement procedure that simplifies structural characterization of drug-stabilized cleavage complexes, we have extended the analysis toward other structurally distinct drugs, m -AMSA and mitoxantrone. Besides the expected drug intercalation, a switch in ribose puckering in the 3'-nucleotide of the cleavage site was robustly observed in the new structures, representing a new mechanism for trapping the Top2 cleavage complex. Analysis of drug-binding modes and the conformational landscapes of the drug-binding pockets provide rationalization of the drugs’ structural-activity relationships and explain why Top2 mutants exhibit differential effects toward each drug. Drug design guidelines were proposed to facilitate the development of isoform-specific Top2-targeting anticancer agents.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 2
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    Geological Society (of London)
    Publication Date: 2017-09-30
    Description: A review of Permian fusuline biostratigraphy is made in this paper in order to improve the correlation of Permian strata globally. Permian fusuline biostratigraphy in the Tethyan and Panthalassan regions can be correlated roughly because the fusulines had good faunal communications between these two regions. However, fusuline faunas from the North American Craton region were devoid of almost all neoschwagerinids and dominated exclusively by schwagerinids during the Guadalupian (Middle Permian) because of the blockage caused by the vast Pangaea supercontinent. This renders the correlation of Middle Permian biostratigraphy and chronostratigraphy between the Tethyan region and North American region challenging. Significant evolutionary key points in fusulines include the first occurrence of Pseudoschwagerina or Sphaeroschwagerina during the earliest Permian, first occurrence of Pamirina and Misellina during the Yakhtashian and Bolorian, and the extinction of all schwagerinids and neoschwagerinids by the end of the Midian.
    Print ISSN: 0305-8719
    Electronic ISSN: 2041-4927
    Topics: Geosciences
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  • 3
    Publication Date: 2017-05-10
    Description: High speed BLDC has the characteristic as larger air gap smaller armature inductance, traditional PWM modulation will produce a great number of high frequency current harmonics which led problem like large torque ripple and serious motor heat. In the meantime traditional PWM modulation use the diode rectifier which cause harmonic pollution in electric power net. To solve the problem above, proposes a new motor controller topology. Using the IGBT device to replace the diode on frequency converter rectifier side, apply the power factor correction technology, reduce the pollution on the grid. Using busbar current modulation on the inverter, driving bridge-arm use 3-phase 6-state open as driving Mode, realize the control on a 10000r/min,10kw BLDC. The results of Simulation on matlab show the topological structure as proposed can effectively improve the network side power factor and reduce the motor armature winding harmonic and motor torque ripple.
    Print ISSN: 1755-1307
    Electronic ISSN: 1755-1315
    Topics: Geography , Geosciences , Physics
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  • 4
    Publication Date: 2013-06-23
    Description: With the rapid accumulation of our knowledge on diseases, disease-related genes and drug targets, network-based analysis plays an increasingly important role in systems biology, systems pharmacology and translational science. The new release of VisANT aims to provide new functions to facilitate the convenient network analysis of diseases, therapies, genes and drugs. With improved understanding of the mechanisms of complex diseases and drug actions through network analysis, novel drug methods (e.g., drug repositioning, multi-target drug and combination therapy) can be designed. More specifically, the new update includes (i) integrated search and navigation of disease and drug hierarchies; (ii) integrated disease–gene, therapy–drug and drug–target association to aid the network construction and filtering; (iii) annotation of genes/drugs using disease/therapy information; (iv) prediction of associated diseases/therapies for a given set of genes/drugs using enrichment analysis; (v) network transformation to support construction of versatile network of drugs, genes, diseases and therapies; (vi) enhanced user interface using docking windows to allow easy customization of node and edge properties with build-in legend node to distinguish different node type. VisANT is freely available at: http://visant.bu.edu .
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 5
    Publication Date: 2013-09-06
    Description: Intravenous immunoglobulin suppresses NLRP1 and NLRP3 inflammasome-mediated neuronal death in ischemic stroke Cell Death and Disease 4, e790 (September 2013). doi:10.1038/cddis.2013.326 Authors: D Yang-Wei Fann, S-Y Lee, S Manzanero, S-C Tang, M Gelderblom, P Chunduri, C Bernreuther, M Glatzel, Y-L Cheng, J Thundyil, A Widiapradja, K-Z Lok, S L Foo, Y-C Wang, Y-I Li, G R Drummond, M Basta, T Magnus, D-G Jo, M P Mattson, C G Sobey & T V Arumugam
    Keywords: IVIgischemic strokeinflammasomecell deathcaspase
    Electronic ISSN: 2041-4889
    Topics: Biology , Medicine
    Published by Springer Nature
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  • 6
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    In:  Pageoph, Edmonton, Conseil de l'Europe, vol. 159, no. 10, pp. 2525-2536, pp. B10410, (ISSN: 1340-4202)
    Publication Date: 2002
    Keywords: Modelling ; Earthquake precursor: prediction research ; accelerating ; seismic Moment ; Energy (of earthquakes) ; release ; cells ; Strain ; Stress ; PAG
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  • 7
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    In:  Pageoph, Taipei, AGU, vol. 157, no. 11/12, pp. 1905-1928, pp. L06307, 2 pp., (ISSN: 1340-4202)
    Publication Date: 2000
    Keywords: Modelling ; Fracture ; Discrete / Distinct Element Method ; Source ; PAG ; Matsuura
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  • 8
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    In:  Pageoph, Corvallis, x + 406 pp., Oregon State University Press, vol. 157, no. 11/12, pp. 2365-2383, pp. L13610, (ISSN: 1340-4202)
    Publication Date: 2000
    Keywords: Modelling ; Earthquake precursor: prediction research ; Non-linear effects ; Tectonics ; SOC ; Stress ; triggering ; Earth tides ; PAG ; Matsuura
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  • 9
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    In:  Pageoph, Corvallis, x + 406 pp., Oregon State University Press, vol. 159, no. 10, pp. 2511-2523, pp. L13610, (ISSN: 1340-4202)
    Publication Date: 2002
    Keywords: Modelling ; Earthquake precursor: prediction research ; seismic Moment ; Energy (of earthquakes) ; release ; critical-point ; hypothesis ; load-unload ; response ; ratio ; PAG
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  • 10
    Publication Date: 2010-08-14
    Description: Dendritic cells (DCs) play a vital role in initiating robust immunity against pathogens as well as maintaining immunological tolerance to self antigens. However, the intracellular signaling networks that program DCs to become tolerogenic remain unknown. We report here that the Wnt-beta-catenin signaling in intestinal dendritic cells regulates the balance between inflammatory versus regulatory responses in the gut. beta-catenin in intestinal dendritic cells was required for the expression of anti-inflammatory mediators such as retinoic acid-metabolizing enzymes, interleukin-10, and transforming growth factor-beta, and the stimulation of regulatory T cell induction while suppressing inflammatory effector T cells. Furthermore, ablation of beta-catenin expression in DCs enhanced inflammatory responses and disease in a mouse model of inflammatory bowel disease. Thus, beta-catenin signaling programs DCs to a tolerogenic state, limiting the inflammatory response.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3732486/" 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/PMC3732486/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Manicassamy, Santhakumar -- Reizis, Boris -- Ravindran, Rajesh -- Nakaya, Helder -- Salazar-Gonzalez, Rosa Maria -- Wang, Yi-Chong -- Pulendran, Bali -- HHSN266 200700006C/PHS HHS/ -- N01 AI50019/AI/NIAID NIH HHS/ -- N01 AI50025/AI/NIAID NIH HHS/ -- R01 AI048638/AI/NIAID NIH HHS/ -- R01 AI056499/AI/NIAID NIH HHS/ -- R01 DK057665/DK/NIDDK NIH HHS/ -- R01DK057665,/DK/NIDDK NIH HHS/ -- R37 AI048638/AI/NIAID NIH HHS/ -- R37 DK057665/DK/NIDDK NIH HHS/ -- R37AI48638,/AI/NIAID NIH HHS/ -- U19 AI057266/AI/NIAID NIH HHS/ -- U19AI057266,/AI/NIAID NIH HHS/ -- U54 AI057157/AI/NIAID NIH HHS/ -- U54AI057157/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2010 Aug 13;329(5993):849-53. doi: 10.1126/science.1188510.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Emory Vaccine Center, and Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, GA 30329, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20705860" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cytokines/metabolism ; Dendritic Cells/*immunology/metabolism ; Gene Expression Profiling ; *Inflammation ; Inflammatory Bowel Diseases/*immunology ; Intestinal Mucosa/cytology/*immunology/metabolism ; Macrophages/immunology/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Oligonucleotide Array Sequence Analysis ; *Self Tolerance ; Signal Transduction ; T-Lymphocytes, Helper-Inducer/cytology/*immunology ; T-Lymphocytes, Regulatory/*immunology ; Tretinoin/metabolism ; Wnt Proteins/metabolism ; beta Catenin/*metabolism
    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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