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Block Card 3775 Airport Highway
No full textThis image was produced by the Auditor's Office in Lucas County, Ohio for tax assessment purposes. Associated dates are approximate. Descriptive terms related to this photograph include: Ranch houses | 3775 Airport Highway (Toledo, Ohio) | Dwelling | South Toledo Area (Toledo, Ohio
Travelers Aid Annual Survey Reveals 3775 Dayton Volunteers Assisted Organization
Get PDFNews release announcing 3775 Dayton residents volunteered to aid Dayton Travelers Aid Society, as reported in an annual survey
Santa Fe (ATSF) 3775 on "Grand Canyon Limited"
No full textA photograph postcard showing the Santa Fe (ATSF) 3775, 4-8-4, on No. 23, "Grand Canyon Limited", passing Heman, OK, 14 cars, 65 mph
Conformisme, radicalisme en machteloosheid: een onderzoek naar de sociaal-culturele en sociaal-economische opvattingen van arbeiders in Vlaanderen
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3775.pdf (Publisher’s version ) (Open Access
Block Card 3775 Green Valley Drive
No full textThis image was produced by the Auditor's Office in Lucas County, Ohio for tax assessment purposes. Associated dates are approximate. Descriptive terms related to this photograph include: 3775 Green Valley Drive (Toledo, Ohio) | Green Valley Addition (Toledo, Ohio) | South Toledo Area (Toledo, Ohio) | Ranch houses | Dwellin
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Abstract 3775: Inhibition of mitochondrial translation by the marine natural product elatol shows potent antileukemia activity
No full textAbstract Targeted signaling inhibitors for hematologic malignancies may lead to limited clinical efficacy due to the outgrowth of subpopulations with alternative pathways independent of the drug target. Recent studies have shown that some forms of hematologic malignancies (Ashton et al., 2018) and solid tumors (Molina et al., 2018) have an energy metabolism highly dependent on mitochondrial oxidative phosphorylation. Tigecycline, a US FDA approved antibiotic, has been shown to inhibit synthesis of mitochondrion-encoded proteins leading to selective lethality in hematologic malignancies reliant on oxidative phosphorylation (Norberg et al., 2017). Combination treatment with the tyrosine-kinase inhibitor (TKI) imatinib and tigecycline eradicated therapy-resistant chronic myelogenous leukemia (CML), both in vitro and in vivo (Kuntz et al., 2017). We have previously reported that elatol, the major compound from algae Laurencia microcladia, is effective against several non-Hodgkin lymphomas and primary CML cells (Peters et al., 2018). In vitro studies showed that elatol inhibits eIF4A1 helicase activity, suppressing cytoplasmic cap-dependent translation initiation. Further assessments using 35-S-methionine incorporation in HEK293T cells treated with single-digit micromolar concentrations of elatol for short periods revealed strong downregulation of mitochondrion-encoded proteins (no transcriptional effect). This was confirmed in CML and acute lymphoblastic leukemia (ALL) cell lines whose 24-hour elatol LD50 ranged from high nanomolar to low micromolar concentrations. This potency was 2-10x higher than for tigecycline in side-by-side comparisons across several leukemia cell lines. Through sedimentation property analysis using sucrose gradients, we established that elatol does not affect integrity of small and large mitochondrial ribosomal units. Although the specific target on the mitochondrial translation apparatus remains elusive, we have uncovered that its mechanism of action differs from that of chloramphenicol, which inhibits translation elongation. Moreover, elatol treatment leads to activation of the integrated stress response (ISR) evidenced by induction of ATF4 and CHOP. We found that elatol activates the ISR through mitochondrial stress in which cleaved DELE1 binds to HRI to phosphorylate eIF2α, a mechanism described in Fessler et al., 2020. In summary, we have performed proof-of-concept studies using HEK293T and HeLa cell lines, isolated mitochondria, and CML and ALL cell lines to reveal that elatol is a potent inhibitor of mitochondrial protein synthesis and mechanistically different from chloramphenicol. Tigecycline’s compelling preclinical data in combination with TKI informed design of a pending clinical trial (NCT02883036). Elatol’s greatly improved potency provides a potential starting point for further optimization of this paradigm. Citation Format: Tyler A. Cunningham, Priyanka Maiti, Antonio Barrientos, Jonathan H. Schatz. Inhibition of mitochondrial translation by the marine natural product elatol shows potent antileukemia activity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3775
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Variations on the Author
Get PDF“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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