1,725,510 research outputs found
Santa Fe (ATSF) 4059
No full textA photograph print showing the Santa Fe (ATSF) 4059, 2-8-2, on mixed freight train No. 37, passing through Shawnee, OK
Chicago, Rock Island & Pacific (RI) 4059
No full textA photograph print showing the Chicago, Rock Island & Pacific (CRIP, RI, or ROCK) 4059, 4-8-2, Chicago. IL
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Abstract 4016: Homogeneous BTK occupancy assay for pharmacodynamic assessment of GS-4059 target engagement
No full textAbstract
Burton’s Tyrosine Kinase (BTK) plays an important role in B cell signaling, cell proliferation and survival. Hence, it is an attractive target for therapeutic intervention in B cell malignancies and autoimmune disorders. GS-4059 (ONO-4059) is a covalent, potent and selective inhibitor of BTK in clinical development for CLL, NHL, and rheumatoid arthritis. Accurate measurement of target coverage in early stage clinical studies is critical to informing dose selection for GS-4059 in more advanced clinical studies. We developed a novel duplex homogeneous BTK occupancy assay to enable quantitative measurement of GS-4059 binding to human BTK for assessing target coverage in the clinic. The assay is based on Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) and simultaneously measures the levels of free BTK (BTK that is not bound to GS-4059 in treated human PBMCs ex vivo or PBMCs from patients treated with GS-4059 in clinical studies) as well as the levels of total BTK protein. We took advantage of the dual wavelength emission property of Terbium (Tb) to serve as energy donor for 2 fluorescent energy acceptors with distinct excitation and emission spectra. We designed and synthesized a GS-4059 analog with biotin conjugate which showed equal potency to GS-4059, suggesting that it binds in the same BTK pocket. To detect free BTK, a Tb-coupled anti-BTK antibody was used as the FRET energy donor and G2-strepavidin-bound biotinylated GS-4059 as the energy acceptor. Total BTK was detected in the same well with a second D2-coupled anti-BTK antibody that binds to a different BTK epitope as the FRET energy acceptor. The use of a common detection reagent in this multiplexed format allows measurement of free and total BTK levels in the same well data. The assay was characterized and qualified using full length purified recombinant human BTK protein and PBMCs derived from healthy volunteers and CLL patients. Preliminary data indicate the assay is also suitable for assessing BTK occupancy in bone marrow derived cells. Using this assay, we evaluated the BTK synthesis rate following a 1 hour high dose (5 μM) treatment of GS-4059 in BTK inhibitor resistant ABC-DLBCL and GCB-DLBCL tumor cells. While negligible new BTK synthesis was observed in BTK inhibitor sensitive DLBCL cells, the free BTK level in the inhibitor resistant tumor cells recovered rapidly post-treatment. In summary, we have established a homogeneous TR-FRET based BTK occupancy assay that simultaneously measures free and total BTK levels in the same well, yielding quantitative BTK occupancy data to support GS-4059 clinical development.
Citation Format: Helen Yu, Hoa Truong, Scott A. Mitchell, John J. Gosink, Julie Lin, Joy Y. Feng, Juliane M. Jürgensmeier, Andrew N. Billin, Ren Xu, Siddhartha Mitra. Homogeneous BTK occupancy assay for pharmacodynamic assessment of GS-4059 target engagement [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4016. doi:10.1158/1538-7445.AM2017-4016</jats:p
Linked collectors and determiners for: Sagehen Creek Field Station (UC-Berkeley) - Birds.
No full textNatural history specimen data linked to collectors and determiners held within, "Sagehen Creek Field Station (UC-Berkeley) - Birds". Claims or attributions were made on Bionomia by volunteer Scribes, <a href="http://bionomia.net/dataset/dc1126b3-4d7d-4059-8108-86d52af10473">https://bionomia.net/dataset/dc1126b3-4d7d-4059-8108-86d52af10473</a> using specimen data from the dataset aggregated by the Global Biodiversity Information Facility, <a href="https://gbif.org/dataset/dc1126b3-4d7d-4059-8108-86d52af10473">https://gbif.org/dataset/dc1126b3-4d7d-4059-8108-86d52af10473</a>. Formatted as a Frictionless Data package
Linked collectors and determiners for: Review of the Inca irroratus species group with description of two new species of Inca LePeletier & Serville, 1828 (Coleoptera, Scarabaeidae, Cetoniinae).
No full textNatural history specimen data linked to collectors and determiners held within, "Review of the Inca irroratus species group with description of two new species of Inca LePeletier & Serville, 1828 (Coleoptera, Scarabaeidae, Cetoniinae)". Claims or attributions were made on Bionomia by volunteer Scribes, <a href="http://bionomia.net/dataset/04bf840b-8ba9-4059-8190-f2454630a714">https://bionomia.net/dataset/04bf840b-8ba9-4059-8190-f2454630a714</a> using specimen data from the dataset aggregated by the Global Biodiversity Information Facility, <a href="https://gbif.org/dataset/04bf840b-8ba9-4059-8190-f2454630a714">https://gbif.org/dataset/04bf840b-8ba9-4059-8190-f2454630a714</a>. Formatted as a Frictionless Data package
Variations on the Author
Full text link“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
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