89,917 research outputs found

    The stem cell E3-ligase Lin-41 promotes liver cancer progression through inhibition of microRNA-mediated gene silencing

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    Lin-41 is a stem cell-specific E3 ligase and a known target of the tumour suppressor microRNA (miRNA) let-7. Lin-41 was recently reported to mediate ubiquitylation and degradation of the miRNA pathway protein Ago2. We demonstrate that Lin-41 is over-expressed in hepatocellular carcinoma (HCC). Lin-41 over-expression correlates with high a-fetoprotein level, high tumour grade and high tumour stage and predicts early tumour recurrence. Lin-41 is a strong predictor of poor long-term survival for patients with HCC. Lin-41 knock-down by RNA interference in HCC cell lines Huh7 and Hep3B suppressed proliferation in vitro and reduced in vivo tumour growth in NOD/SCID mice. On the other hand, over-expression of Lin-41 in the HCC cell line SK-Hep1 enhanced tumourigenicity. Over-expression and knock-down of Lin-41 led to inverse changes in the levels of Ago1 and Ago2 proteins. Over-expression of Ago1 and Ago2 reduced in vivo tumour growth. Lin-41 over-expression suppressed let-7 activity in HCC cell lines and expression of Lin-41 enhanced the expression of let-7-regulated oncogenes c-Myc, Lin-28B, HMGA2 and type 1 insulin-like growth factor receptor (IGF1R). Expression of Lin-28B and c-Myc enhanced the expression of Lin-41. Chromatin immunoprecipitation and reporter assays revealed direct association of c-Myc with the Lin-41 promoter, resulting in transcriptional transactivation. Our results indicate that Lin-41 plays an important role in the growth of HCC by regulating RISC complex proteins Ago1 and Ago2 to inhibit miRNA-mediated gene silencing and promote the expression of oncogenic proteins. Lin-41 is also a strong prognostic factor for patients with HCC. Copyright (C) 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd

    Society of Composers Region VI Conference - Concert 2 Thursday. February 9. 2006 8:00 p.m. Lillian H. Duncan Recital Hall

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    Program: Falling through Crimson and Lead / Suzanne Sorkin -- Madison Sketchbook / John G. Bilotta -- Nocturne No.3 / Francisco Castillo Trigueros -- Schematic Nocturne / Bruce Bennett -- Turning / Derek Bermel -- Once It Was / Trent Hanna -- Interaction / Mei-Fang Lin -- Dialogue for two pianos / Florie Namir.No program is available for this performance

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    "Third Generation"-Type Functional Tris(2-pyridyl)borate Ligands and their Transition-Metal Complexes

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    Phenyltris(2-pyridyl)borates (Tpyb) are a promising class of tripodal “scorpionate”-type ligands with potential utility in the development of transition metal complexes with interesting optical, electronic or magnetic properties, and as building blocks to metallosupramolecular polymers. We report here a new class of “third generation”-type Tpyb ligands that contain different functional groups attached to the boron-bound aryl moiety. The synthesis, characterization and metal ion complexation behavior of ligands with iodo and trimethylsilyl groups is discussed. The electrochemical and absorption characteristics of the corresponding low-spin Fe(II) and Ru(II) complexes are compared. We demonstrate the further elaboration of the iodo derivatives with alkynes via Sonogashira-Hagihara coupling, a process that proceeds with high yield for the Fe(II) and Ru(II) complexes, but not for the free ligand. The borylation of the silyl-substituted Ru(II) complex with BBr3 was also investigated. In addition to the expected borylation product, Ru(Tpyb-Bpin)2, the replacement of one (major product) or two phenyl groups is observed, suggesting that electrophilic borylation occurs at both the C(Ph)-Si and the C(Ph)-B aromatic carbons. The successful attachment of a range of different functional groups at the periphery of the Tpyb metal complexes is expected to provide opportunities to access new polymeric materials via C-C coupling or click-type reactions.Peer reviewe

    The road from London to Chichester in com, Suffex : containing 63 mile 2 furlongs vizt. : from ye standard in Cornhill London to Guilford in com Surry ...

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    Relief shown pictorially.; Road strip map in six sections, with numbered distances along road.; Orientation of north shown in each section..; Derived from John Ogilby's Britannia.; 39 in lower right corner.; Decorative cartouche around title statement

    Citizen piece by Portland author John Preston on censorship.

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    Citizen piece by Portland author John Preston on censorship

    Feature article on AIDS by Portland author John Preston.

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    Feature article on AIDS by Portland author John Preston

    Polynesia [cartographic material] /

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    Map of Polynesia, with eastern Australia as Terra Australis, showing the Pacific islands, population, religions, number of missionaries and native assistants.; Imprint on map: London: Published by John Snow, 35 Paternsoter Row.; Prime meridian: Greenwich.; Plate from: A narrative of missionary enterprises in the South Sea Islands / John Williams. London : Published for the author, by J. Snow, 1837.; Also available in an electronic version via the internet at: http://nla.gov.au/nla.map-rm3970

    Chili.

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    Relief shown pictorially.; Oriented with north to the left.; Representing part of Chile. East of the Andes is filled with decoration to make up for lack of knowledge. It includes a compass rose, rhumb lines, sailing ships and a large cartouche on top combining title and scales.; Arnold Montanus's maps from his atlas were sold separately and were included in John Ogilby's "America: being the latest and most accurate description of the New World adorned with maps and sculptures by John Ogilby.

    Seeing the world anew : the radical vision of Martin Waldseemüller's 1507 & 1516 world maps /

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    9781929154470 (ISBN). 192915447X (ISBN). First edition 2012. Accompanied by 2 foldeds map in front and back pockets: 1507 map -- 1516 map.; Includes bibliographical references: pages 98-107.; Maps from pockets also available online http://nla.gov.au/nla.map-vn6254227; Original version of the 1507 map: Universalis cosmographiae secundum Ptholomaei traditionem et Americi Vespucii alioru que lustrationes. [St. Dié, France? : s.n., 1507]; Original version of the 1516 map: Carta marina, navigatoria Portugallen, navigationes atque tocius cogniti orbis terre marisque formam naturamq[u]e situs et terminos nostris temporibus recognitos et ab antiquorum traditione differentes eciam quor[um] vetusti non meminerunt auctores hec generaliter indicat / consumatum est in oppido S. Deodati compositione et digestione Martini Waldseemuller Ilacomili. [St. Dié, France? : s.n., 1516]. Prologue: In a Renaissance Vision, a Glimpse of the Modern / John W. Hessler -- "An island surrounded on all sides by sea" : The World Map, 1507 / John W. Hessler -- "Land of Cuba, part of Asia" : The Carta marina, 1516 / Chet Van Duzer -- Epilogue: A Renaissance That Resonates Still / John W. Hessler -- Notes -- Afterword / Ralph E. Ehrenberg -- About the authors -- Acknowledgments -- The Maps: The 1507 World Map, 12 sheets, with commentary -- Composite: front pocket -- The 1516 Carta marina, 13 sheets, with commentary -- Composite: back pocket
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