1,727,526 research outputs found

    Steam engine #2384, Nelson

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    Engine #2384 at Nelson, July 1st, 1950

    Mandurama photograph collection [2384] [picture] /

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    Also available in an electronic version via the Internet at: http://nla.gov.au/nla.pic-an8526486-2384

    2384. Jacques de Vitry

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    2384. Jacques de Vitry. In: Molinier Auguste. Les Sources de l'histoire de France - Des origines aux guerres d'Italie (1494). III. Les Capétiens, 1180-1328. Paris : A. Picard et fils, 1903. pp. 49-50

    The synthetic diazonamide DZ-2384 has distinct effects on microtubule curvature and dynamics without neurotoxicity

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    Microtubule-targeting agents (MTAs) are widely used anticancer agents, but toxicities such as neuropathy limit their clinical use. MTAs bind to and alter the stability of microtubules, causing cell death in mitosis. We describe DZ-2384, a preclinical compound that exhibits potent antitumor activity in models of multiple cancer types. It has an unusually high safety margin and lacks neurotoxicity in rats at effective plasma concentrations. DZ-2384 binds the vinca domain of tubulin in a distinct way, imparting structurally and functionally different effects on microtubule dynamics compared to other vinca-binding compounds. X-ray crystallography and electron microscopy studies demonstrate that DZ-2384 causes straightening of curved protofilaments, an effect proposed to favor polymerization of tubulin. Both DZ-2384 and the vinca alkaloid vinorelbine inhibit microtubule growth rate; however, DZ-2384 increases the rescue frequency and preserves the microtubule network in nonmitotic cells and in primary neurons. This differential modulation of tubulin results in a potent MTA therapeutic with enhanced safety

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Art. 2384 - Poteri di rappresentanza

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    Commento all'art. 2384 del Codice Civile: 1. Il potere di rappresentanza: titolarità ed esercizio fra autonomia statutaria e disciplina legale. 2. Il congegno rappresentativo di società per azioni: premesse teoriche e cenni evolutivi. 3. Atti estranei all’oggetto sociale. 4. Il difetto di titolarità del potere di rappresentanza. Rappresentanza e gestione per delega. La clausola di firma congiunta. 5. Tutela del terzo ed exceptio doli. 6. Rappresentanza e limiti legali. Premessa. 7. (Segue). La rilevanza esterna del procedimento decisorio consiliare. Il problema delle autorizzazioni assembleari

    MLS-2384, a new 6-bromoindirubin derivative with dual JAK/Src kinase inhibitory activity, suppresses growth of diverse cancer cells

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    Janus kinase (JAK) and Src kinase are the two major tyrosine kinase families upstream of signal transducer and activator of transcription (STAT). Among the seven STAT family proteins, STAT3 is constitutively activated in many diverse cancers. Upon activation, JAK and Src kinases phosphorylate STAT3, and thereby promote cell growth and survival. MLS-2384 is a novel 6-bromoindirubin derivative with a bromo-group at the 6-position on one indole ring and a hydrophilic group at the 3'-position on the other indole ring. In this study, we investigated the kinase inhibitory activity and anticancer activity of MLS-2384. Our data from in vitro kinase assays, cell viability analyses, western blotting analyses, and animal model studies, demonstrate that MLS-2384 is a dual JAK/Src kinase inhibitor, and suppresses growth of various human cancer cells, such as prostate, breast, skin, ovarian, lung, and liver. Consistent with the inactivation of JAK and Src kinases, phosphorylation of STAT3 was inhibited in a dose-dependent manner in the cancer cells treated with MLS-2384. STAT3 downstream proteins involved in cell proliferation and survival, such as c-Myc and Mcl-1, are downregulated by MLS- 2384 in prostate cancer cells, whereas survivin is downregulated in A2058 cells. In these two cancer cell lines, PARP is cleaved, indicating that MLS-2384 induces apoptosis in human melanoma and prostate cancer cells. Importantly, MLS- 2384 suppresses tumor growth with low toxicity in a mouse xenograft model of human melanoma. Taken together, MLS-2384 demonstrates dual JAK/Src inhibitory activity and suppresses tumor cell growth both in vitro and in vivo. Our findings support further development of MLS-2384 as a potential small-molecule therapeutic agent that targets JAK, Src, and STAT3 signaling in multiple human cancer cells. © 2014 Landes Bioscience

    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

    Loney, Lewis B., 1851-1922 (SC 2384)

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    Finding aid only for Manuscripts Small Collection 2384. Diary of daily events recorded by Lewis B. Loney, who was a young man still working on his father\u27s Ohio County, Kentucky farm. He records farming activities, social occasions, church and school attendance, medical issues, and other happenings that occurred in the area near his home. The manuscript is only partially legible due to oil damage
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