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  • 1
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    Repression of the IgH enhancer in teratocarcinoma cells associated with a novel octamer factor (1989)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1989-01-27
    Description: Embryonal carcinoma (EC) cell lines are models for early cells in mouse embryogenesis. A 300-base pair fragment of the heavy chain enhancer was inactive in F9 EC cells, unlike in other nonlymphoid cells where it has significant activity. Alterations of the octamer motif increased enhancer activity. Nuclear extracts from F9 cells contained an octamer binding protein (NF-A3) that was unique to EC cells; the amount of NF-A3 decreased upon differentiation. It is proposed that NF-A3 represses specific regulatory sequences that contain the octamer motif. Thus, the same DNA sequence mediates either negative or positive transcriptional effects, depending on the cell type.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lenardo, M J -- Staudt, L -- Robbins, P -- Kuang, A -- Mulligan, R C -- Baltimore, D -- CA 01074/CA/NCI NIH HHS/ -- HD0063/HD/NICHD NIH HHS/ -- HL37569/HL/NHLBI NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1989 Jan 27;243(4890):544-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research, Cambridge, MA 02142.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2536195" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bucladesine/pharmacology ; Cell Differentiation ; DNA/metabolism ; Embryonal Carcinoma Stem Cells ; *Enhancer Elements, Genetic ; Immunoglobulin Heavy Chains/*genetics ; Macromolecular Substances ; Mice ; Mutation ; Neoplastic Stem Cells/*metabolism ; RNA, Messenger/biosynthesis ; Regulatory Sequences, Nucleic Acid ; Repressor Proteins/genetics ; Transcription, Genetic ; Transfection ; Tretinoin/pharmacology ; Tumor Cells, Cultured
    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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  • 2
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    Demonstration that CFTR is a chloride channel by alteration of its anion selectivity (1991)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1991-07-12
    Description: Expression of the cystic fibrosis transmembrane conductance regulator (CFTR) generates adenosine 3',5'-monophosphate (cAMP)-regulated chloride channels, indicating that CFTR is either a chloride channel or a chloride channel regulator. To distinguish between these possibilities, basic amino acids in the putative transmembrane domains were mutated. The sequence of anion selectivity of cAMP-regulated channels in cells containing either endogenous or recombinant CFTR was bromide greater than chloride greater than iodide greater than fluoride. Mutation of the lysines at positions 95 or 335 to acidic amino acids converted the selectivity sequence to iodide greater than bromide greater than chloride greater than fluoride. These data indicate that CFTR is a cAMP-regulated chloride channel and that lysines 95 and 335 determine anion selectivity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Anderson, M P -- Gregory, R J -- Thompson, S -- Souza, D W -- Paul, S -- Mulligan, R C -- Smith, A E -- Welsh, M J -- New York, N.Y. -- Science. 1991 Jul 12;253(5016):202-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1712984" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Chloride Channels ; Chlorides/*physiology ; Cyclic AMP/physiology ; Cystic Fibrosis/physiopathology ; Cystic Fibrosis Transmembrane Conductance Regulator ; DNA Mutational Analysis ; Electric Conductivity ; HeLa Cells ; Humans ; In Vitro Techniques ; Ion Channels/genetics/*physiology ; Membrane Glycoproteins/genetics/physiology ; Membrane Potentials ; Membrane Proteins/genetics/*physiology ; Molecular Sequence Data ; Transfection
    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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    Implantation of vascular grafts lined with genetically modified endothelial cells (1989)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1989-06-16
    Description: The possibility of using the vascular endothelial cell as a target for gene replacement therapy was explored. Recombinant retroviruses were used to transduce the lacZ gene into endothelial cells harvested from mongrel dogs. Prosthetic vascular grafts seeded with the genetically modified cells were implanted as carotid interposition grafts into the dogs from which the original cells were harvested. Analysis of the graft 5 weeks after implantation revealed genetically modified endothelial cells lining the luminal surface of the graft. This technology could be used in the treatment of atherosclerosis disease and the design of new drug delivery systems.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wilson, J M -- Birinyi, L K -- Salomon, R N -- Libby, P -- Callow, A D -- Mulligan, R C -- New York, N.Y. -- Science. 1989 Jun 16;244(4910):1344-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute, Cambridge, MA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2734614" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Blood Vessel Prosthesis ; Carotid Arteries/surgery ; Cells, Cultured ; Dogs ; Endothelium, Vascular/*cytology/physiology/transplantation ; Genetic Vectors ; Retroviridae/genetics ; *Transfection
    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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    An aneuploid mouse strain carrying human chromosome 21 with Down syndrome phenotypes (2005)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2005-09-24
    Description: Aneuploidies are common chromosomal defects that result in growth and developmental deficits and high levels of lethality in humans. To gain insight into the biology of aneuploidies, we manipulated mouse embryonic stem cells and generated a trans-species aneuploid mouse line that stably transmits a freely segregating, almost complete human chromosome 21 (Hsa21). This "transchromosomic" mouse line, Tc1, is a model of trisomy 21, which manifests as Down syndrome (DS) in humans, and has phenotypic alterations in behavior, synaptic plasticity, cerebellar neuronal number, heart development, and mandible size that relate to human DS. Transchromosomic mouse lines such as Tc1 may represent useful genetic tools for dissecting other human aneuploidies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1378183/" 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/PMC1378183/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉O'Doherty, Aideen -- Ruf, Sandra -- Mulligan, Claire -- Hildreth, Victoria -- Errington, Mick L -- Cooke, Sam -- Sesay, Abdul -- Modino, Sonie -- Vanes, Lesley -- Hernandez, Diana -- Linehan, Jacqueline M -- Sharpe, Paul T -- Brandner, Sebastian -- Bliss, Timothy V P -- Henderson, Deborah J -- Nizetic, Dean -- Tybulewicz, Victor L J -- Fisher, Elizabeth M C -- 076700/Wellcome Trust/United Kingdom -- MC_U117512674/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2005 Sep 23;309(5743):2033-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurodegenerative Disease, Institute of Neurology, Queen Square, London WC1N 3BG, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16179473" target="_blank"〉PubMed〈/a〉
    Keywords: *Aneuploidy ; Animals ; Behavior, Animal ; Brain/pathology ; Cell Count ; Cell Line ; Chimera ; *Chromosomes, Human, Pair 21 ; *Disease Models, Animal ; *Down Syndrome/genetics/physiopathology ; Embryo, Mammalian/cytology ; Facial Bones/pathology ; Female ; Gene Expression ; *Genetic Engineering ; Genetic Markers ; Heart Defects, Congenital/embryology ; Hippocampus/physiopathology ; Humans ; Long-Term Potentiation ; Lymphocyte Activation ; Male ; Maze Learning ; Memory ; Mice ; Mice, Inbred Strains ; *Mice, Transgenic ; Neurons/cytology ; Oligonucleotide Array Sequence Analysis ; Phenotype ; Skull/pathology ; Stem Cells ; Synaptic Transmission ; T-Lymphocytes/immunology
    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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    "Stemness": transcriptional profiling of embryonic and adult stem cells (2002)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2002-09-14
    Description: The transcriptional profiles of mouse embryonic, neural, and hematopoietic stem cells were compared to define a genetic program for stem cells. A total of 216 genes are enriched in all three types of stem cells, and several of these genes are clustered in the genome. When compared to differentiated cell types, stem cells express a significantly higher number of genes (represented by expressed sequence tags) whose functions are unknown. Embryonic and neural stem cells have many similarities at the transcriptional level. These results provide a foundation for a more detailed understanding of stem cell biology.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ramalho-Santos, Miguel -- Yoon, Soonsang -- Matsuzaki, Yumi -- Mulligan, Richard C -- Melton, Douglas A -- P60 HL54785/HL/NHLBI NIH HHS/ -- R24 DK56947/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2002 Oct 18;298(5593):597-600. Epub 2002 Sep 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology and Howard Hughes Medical Institute (HHMI), Harvard University, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12228720" target="_blank"〉PubMed〈/a〉
    Keywords: ATP-Binding Cassette Transporters/genetics/metabolism ; Animals ; Bone Marrow Cells/physiology ; Cell Differentiation ; DNA Helicases/genetics/metabolism ; Embryo, Mammalian/*cytology ; Expressed Sequence Tags ; *Gene Expression ; *Gene Expression Profiling ; Gene Expression Regulation ; Hematopoietic Stem Cells/*physiology ; Lateral Ventricles/cytology ; Mice ; Mice, Inbred C57BL ; Neurons/*cytology ; Oligonucleotide Array Sequence Analysis ; Oxidative Stress ; Reproducibility of Results ; Signal Transduction ; Stem Cells/*physiology ; Transcription, Genetic
    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
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    The basic science of gene therapy (1993)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1993-05-14
    Description: The development over the past decade of methods for delivering genes to mammalian cells has stimulated great interest in the possibility of treating human disease by gene-based therapies. However, despite substantial progress, a number of key technical issues need to be resolved before gene therapy can be safely and effectively applied in the clinic. Future technological developments, particularly in the areas of gene delivery and cell transplantation, will be critical for the successful practice of gene therapy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mulligan, R C -- New York, N.Y. -- Science. 1993 May 14;260(5110):926-32.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge 02142.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8493530" target="_blank"〉PubMed〈/a〉
    Keywords: Adenoviridae/genetics ; Animals ; *Genetic Therapy ; Genetic Vectors ; Hematologic Diseases/therapy ; Hematopoietic Stem Cells ; Humans ; Liver Diseases/therapy ; Lung Diseases/therapy ; Neoplasms/therapy ; Retroviridae/genetics ; Tissue Transplantation ; *Transfection ; Viruses/genetics
    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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  • 7
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    PTH/PTHrP receptor in early development and Indian hedgehog-regulated bone growth (1996)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1996-08-02
    Description: The PTH/PTHrP receptor binds to two ligands with distinct functions: the calcium-regulating hormone, parathyroid hormone (PTH), and the paracrine factor, PTH-related protein (PTHrP). Each ligand, in turn, is likely to activate more than one receptor. The functions of the PTH/PTHrP receptor were investigated by deletion of the murine gene by homologous recombination. Most PTH/PTHrP receptor (-/-) mutant mice died in mid-gestation, a phenotype not observed in PTHrP (-/-) mice, perhaps because of the effects of maternal PTHrP. Mice that survived exhibited accelerated differentiation of chondrocytes in bone, and their bones, grown in explant culture, were resistant to the effects of PTHrP and Sonic hedgehog. These results suggest that the PTH/PTHrP receptor mediates the effects of Indian Hedgehog and PTHrP on chondrocyte differentiation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lanske, B -- Karaplis, A C -- Lee, K -- Luz, A -- Vortkamp, A -- Pirro, A -- Karperien, M -- Defize, L H -- Ho, C -- Mulligan, R C -- Abou-Samra, A B -- Juppner, H -- Segre, G V -- Kronenberg, H M -- DK 47038/DK/NIDDK NIH HHS/ -- DK 47237/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1996 Aug 2;273(5275):663-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8662561" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Bone Development ; Cartilage/*cytology/metabolism ; Cell Differentiation ; Cell Division ; Cloning, Molecular ; Culture Techniques ; Feedback ; Gene Deletion ; Gene Targeting ; Growth Plate/*cytology/metabolism ; Hedgehog Proteins ; Mice ; Mice, Inbred C57BL ; Osteoblasts/cytology ; *Osteogenesis ; Parathyroid Hormone ; Parathyroid Hormone-Related Protein ; Protein Biosynthesis ; Proteins/pharmacology/physiology ; Receptor, Parathyroid Hormone, Type 1 ; Receptors, Parathyroid Hormone/genetics/*physiology ; Stem Cells ; *Trans-Activators
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
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    Expression of a bacterial gene in mammalian cells (1980)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1980-09-19
    Description: Transfection of cultured monkey kidney cells with recombinant DNA constructed with a cloned Escherichia coli gene that codes for xanthine-guanine phosphoribosyltransferase and several different SV40 DNA-based vectors, results in the synthesis of readily measurable quantities of the bacterial enzyme. Moreover, the physiological defect in purine nucleotide synthesis characteristic of human Lesch-Nyhan cells can be overcome by the introduction of the bacterial gene into these cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mulligan, R C -- Berg, P -- New York, N.Y. -- Science. 1980 Sep 19;209(4463):1422-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6251549" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cells, Cultured ; Cloning, Molecular/methods ; DNA, Bacterial/*genetics ; *DNA, Recombinant ; Escherichia coli ; *Genes ; Haplorhini ; Humans ; Hypoxanthine Phosphoribosyltransferase/genetics ; Lesch-Nyhan Syndrome/*genetics ; Pentosyltransferases/*genetics ; Simian virus 40/genetics ; Transduction, Genetic ; Transformation, Genetic
    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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    Tissue-specific and ectopic expression of genes introduced into transgenic mice by retroviruses (1986)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1986-12-12
    Description: Recombinant retroviruses containing the complete genomic human beta globin gene (under the control of its own promoter) and the bacterial neomycin phosphotransferase gene (under the control of the normal or enhancerless viral promoter) were used to derive transgenic mouse strains by infection of preimplantation embryos. Expression of the beta globin gene in hematopoietic tissues was observed in all transgenic strains. In addition, one strain showed ectopic expression of beta globin in the same tissues that also expressed high levels of RNA from the viral promoter. It is likely that expression from the long terminal repeat (LTR), in contrast to expression from the internal promoter, is dependent on the site of integration. Thus, retroviral vectors can be used for tissue-specific expression of foreign genes in transgenic mice, as well as for the identification of loci that allow developmental activation of a provirus.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Soriano, P -- Cone, R D -- Mulligan, R C -- Jaenisch, R -- HD-19105/HD/NICHD NIH HHS/ -- P01-CA38497/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1986 Dec 12;234(4782):1409-13.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3024318" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Gene Expression Regulation ; Globins/genetics ; Humans ; Kanamycin Kinase ; Mice/genetics ; Phosphotransferases/genetics ; Promoter Regions, Genetic ; RNA, Viral/immunology ; Repetitive Sequences, Nucleic Acid ; Retroviridae/*genetics
    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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  • 10
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    Tissue-specific expression of functionally rearranged lambda 1 Ig gene through a retrovirus vector (1987)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1987-05-22
    Description: To explore the potential use of retrovirus vectors for the transfer of genomic DNA sequences into mammalian cells, recombinant retroviral genomes were constructed that encode a functionally rearranged murine lambda 1 immunoglobulin gene. Several of these genomes could be transmitted intact to recipient cells by viral infection, although successful transmission depended both on the orientation of the lambda 1 sequences and on their specific placement within vector sequences. The lambda 1 gene transduced by viral infection was expressed in a cell lineage-specific manner, albeit at lower levels than endogenous lambda 1 gene expression in cells from the B-lymphocyte lineage. Vectors yielding integrated proviruses that lacked viral transcriptional enhancer sequences were used to show that neither viral transcription nor the viral transcriptional sequences themselves had any effect on the tissue specificity of lambda 1 gene expression or the absolute amount of lambda 1 transcription. Vector transcription did, however, dramatically decrease the amount of lambda 1 protein that could be detected in tranduced cells. These results suggest that retrovirus vectors may be useful reagents not only for the expression of complementary DNA sequences but also for studies of tissue-specific transcription in mammalian cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cone, R D -- Reilly, E B -- Eisen, H N -- Mulligan, R C -- CA26712/CA/NCI NIH HHS/ -- CA38497/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1987 May 22;236(4804):954-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3107128" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; B-Lymphocytes/immunology ; Cells, Cultured ; Enhancer Elements, Genetic ; *Genes ; *Genes, Viral ; Genetic Vectors ; Immunoglobulin lambda-Chains/*genetics ; Retroviridae/*genetics ; *Transcription, Genetic
    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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