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  • American Association for the Advancement of Science (AAAS)  (9)
  • 1
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    Complexity in natural landform patterns (1999)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1999-04-02
    Description: Patterns in nature, such as meandering rivers and sand dunes, display complex behavior seemingly at odds with their simplicity of form. Existing approaches to modeling natural landform patterns, reductionism and universality, are incompatible with the nonlinear, open nature of natural systems. An alternative modeling methodology based on the tendency of natural systems to self-organize in temporal hierarchies is described.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Werner -- New York, N.Y. -- Science. 1999 Apr 2;284(5411):102-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Complex Systems Laboratory, Cecil and Ida Green Institute of Geophysics and Planetary Physics, University of California-San Diego, La Jolla, CA 92093-0225, USA. E-mail: bwerner@ucsd.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10102803" 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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  • 2
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    Tracking cancer drugs in living cells by thermal profiling of the proteome (2014)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2014-10-04
    Description: The thermal stability of proteins can be used to assess ligand binding in living cells. We have generalized this concept by determining the thermal profiles of more than 7000 proteins in human cells by means of mass spectrometry. Monitoring the effects of small-molecule ligands on the profiles delineated more than 50 targets for the kinase inhibitor staurosporine. We identified the heme biosynthesis enzyme ferrochelatase as a target of kinase inhibitors and suggest that its inhibition causes the phototoxicity observed with vemurafenib and alectinib. Thermal shifts were also observed for downstream effectors of drug treatment. In live cells, dasatinib induced shifts in BCR-ABL pathway proteins, including CRK/CRKL. Thermal proteome profiling provides an unbiased measure of drug-target engagement and facilitates identification of markers for drug efficacy and toxicity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Savitski, Mikhail M -- Reinhard, Friedrich B M -- Franken, Holger -- Werner, Thilo -- Savitski, Maria Falth -- Eberhard, Dirk -- Martinez Molina, Daniel -- Jafari, Rozbeh -- Dovega, Rebecca Bakszt -- Klaeger, Susan -- Kuster, Bernhard -- Nordlund, Par -- Bantscheff, Marcus -- Drewes, Gerard -- New York, N.Y. -- Science. 2014 Oct 3;346(6205):1255784. doi: 10.1126/science.1255784. Epub 2014 Oct 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cellzome GmbH, Molecular Discovery Research, GlaxoSmithKline, Meyerhofstrasse 1, Heidelberg, Germany. mikhail.m.savitski@gsk.com marcus.x.bantscheff@gsk.com gerard.c.drewes@gsk.com. ; Cellzome GmbH, Molecular Discovery Research, GlaxoSmithKline, Meyerhofstrasse 1, Heidelberg, Germany. ; Division of Biophysics, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden. ; Department of Proteomics and Bioanalytics, Technische Universitat Munchen, Emil Erlenmeyer Forum 5, Freising, Germany. German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany. ; Division of Biophysics, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden. Centre for Biomedical Structural Biology, Nanyang Technological University, Singapore.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25278616" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphatases/metabolism ; Antineoplastic Agents/*pharmacology ; Hot Temperature ; Humans ; K562 Cells ; Ligands ; Protein Binding ; Protein Denaturation ; Protein Stability ; Proteome/*drug effects ; Proteomics/*methods
    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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  • 3
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    Self-organization of sorted patterned ground (2003)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2003-01-18
    Description: Striking circular, labyrinthine, polygonal, and striped patterns of stones and soil self-organize in many polar and high alpine environments. These forms emerge because freeze-thaw cycles drive an interplay between two feedback mechanisms. First, formation of ice lenses in freezing soil sorts stones and soil by displacing soil toward soil-rich domains and stones toward stone-rich domains. Second, stones are transported along the axis of elongate stone domains, which are squeezed and confined as freezing soil domains expand. In a numerical model implementing these feedbacks, circles, labyrinths, and islands form when sorting dominates; polygonal networks form when stone domain squeezing and confinement dominate; and stripes form as hillslope gradient is increased.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kessler, M A -- Werner, B T -- New York, N.Y. -- Science. 2003 Jan 17;299(5605):380-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Complex Systems Laboratory, Cecil and Ida Green Institute of Geophysics and Planetary Physics, University of California, San Diego, La Jolla, CA 92093, USA. mkessler@es.ucsc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12532013" 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
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  • 4
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    Requirement for a peptidoglycan recognition protein (PGRP) in Relish activation and antibacterial immune responses in Drosophila (2002)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2002-03-02
    Description: Components of microbial cell walls are potent activators of innate immune responses in animals. For example, the mammalian TLR4 signaling pathway is activated by bacterial lipopolysaccharide and is required for resistance to infection by Gram-negative bacteria. Other components of microbial surfaces, such as peptidoglycan, are also potent activators of innate immune responses, but less is known about how those components activate host defense. Here we show that a peptidoglycan recognition protein, PGRP-LC, is absolutely required for the induction of antibacterial peptide genes in response to infection in Drosophila and acts by controlling activation of the NF-kappaB family transcription factor Relish.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Choe, Kwang-Min -- Werner, Thomas -- Stoven, Svenja -- Hultmark, Dan -- Anderson, Kathryn V -- New York, N.Y. -- Science. 2002 Apr 12;296(5566):359-62. Epub 2002 Feb 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Biology Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11872802" target="_blank"〉PubMed〈/a〉
    Keywords: Active Transport, Cell Nucleus ; Alternative Splicing ; Animals ; Antimicrobial Cationic Peptides/genetics/metabolism ; Carrier Proteins/genetics/*metabolism ; Cell Nucleus/metabolism ; Drosophila/genetics/*immunology/metabolism/microbiology ; Drosophila Proteins/*metabolism ; Escherichia coli/immunology ; Exons ; Expressed Sequence Tags ; Gene Expression Regulation ; Genes, Insect ; *Immunity, Innate ; Insect Proteins/genetics/metabolism ; Lipopolysaccharides/immunology/metabolism/pharmacology ; Mutation ; Peptidoglycan/immunology/metabolism/pharmacology ; Phenotype ; Protein Isoforms ; RNA, Double-Stranded ; Transcription Factors/*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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  • 5
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    Beach cusps as self-organized patterns (1993)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1993-05-14
    Description: Computer simulations of flow and sediment transport in the swash zone on a beach demonstrate that a model that couples local flow acceleration and alongshore surface gradient is sufficient to produce uniformly spaced beach cusps. The characteristics of the simulated cusps and the conditions under which they form are in reasonable agreement with observations of natural cusps. The self-organization mechanism in the model is incompatible with an accepted model in which standing alongshore waves drive the regular pattern of erosion and deposition that gives rise to beach cusps. Because the models make similar predictions, it is concluded that currently available observational data are insufficient for discrimination between them.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Werner, B T -- Fink, T M -- New York, N.Y. -- Science. 1993 May 14;260(5110):968-71.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17818387" target="_blank"〉PubMed〈/a〉
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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
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    The architecture of transcription elongation (2017)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2017-09-01
    Keywords: Biochemistry
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
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    Peace and virtue (1986)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1986-12-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Werner, B T -- New York, N.Y. -- Science. 1986 Dec 12;234(4782):1312.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17755050" target="_blank"〉PubMed〈/a〉
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    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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    The Mitsunobu reaction, reimagined (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
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  • 9
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    Click chemistry enables preclinical evaluation of targeted epigenetic therapies (2017)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2017-06-30
    Description: The success of new therapies hinges on our ability to understand their molecular and cellular mechanisms of action. We modified BET bromodomain inhibitors, an epigenetic-based therapy, to create functionally conserved compounds that are amenable to click chemistry and can be used as molecular probes in vitro and in vivo. We used click proteomics and click sequencing to explore the gene regulatory function of BRD4 (bromodomain containing protein 4) and the transcriptional changes induced by BET inhibitors. In our studies of mouse models of acute leukemia, we used high-resolution microscopy and flow cytometry to highlight the heterogeneity of drug activity within tumor cells located in different tissue compartments. We also demonstrate the differential distribution and effects of BET inhibitors in normal and malignant cells in vivo. This study provides a potential framework for the preclinical assessment of a wide range of drugs.
    Keywords: Medicine, Diseases
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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