1,722,770 research outputs found

    Technical Report 0-6766-P2

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    Summary of workshop presentations on TxDOT Project 0-6766: A Generic Mode Choice Model Applicable for Small and Medium-Sized MPOs

    Genome sequence of Wickerhamomyces anomalus DSM 6766 reveals genetic basis of biotechnologically important antimicrobial activities

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    Schneider J, Rupp O, Trost E, et al. Genome sequence of Wickerhamomyces anomalus DSM 6766 reveals genetic basis of biotechnologically important antimicrobial activities. FEMS Yeast Research. 2012;12(3):382-386.The ascomycetous yeast Wickerhamomyces anomalus (formerly Pichia anomala and Hansenula anomala) exhibits antimicrobial activities and flavoring features that are responsible for its frequent association with food, beverage and feed products. However, limited information on the genetic background of this yeast and its multiple capabilities are currently available. Here, we present the draft genome sequence of the neotype strain W. anomalus DSM 6766. On the basis of pyrosequencing, a de novo assembly of this strain resulted in a draft genome sequence with a total size of 25.47 Mbp. An automatic annotation using RAPYD generated 11 512 protein-coding sequences. This annotation provided the basis to analyse metabolic capabilities, phylogenetic relationships, as well as biotechnologically important features and yielded novel candidate genes of W. anomalus DSM 6766 coding for proteins participating in antimicrobial activities

    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

    Abstract 3476: Mechanistic evaluation of VS-6766 (dual RAF/MEK inhibitor) and defactinib (FAK inhibitor) in low-grade serous ovarian cancer models with correlations to clinical response

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    Background: Low-grade serous ovarian cancer (LGSOC) constitutes up to 10% of all ovarian cancer and has clinical and molecular characteristics (resistance to chemotherapy, presence of RAS/RAF mutations, lack of TP53 mutations) distinct from high-grade serous ovarian cancer. Here, we characterized the effects of the dual RAF/MEK inhibitor VS-6766 and the FAK inhibitor defactinib on signal transduction and viability in LGSOC cell lines and patient-derived organoids. To correlate molecular characteristics with clinical response, we characterized genomic alterations in archival tumor samples from patients with LGSOC treated with the combination of VS-6766 and defactinib on a clinical trial (FRAME).Material and Methods: We exposed 5 LGSOC cell lines to clinical Cmax concentrations adjusted for protein binding of VS-6766 and defactinib. We quantified phospho- and total proteins (n=66) with an antibody-bead based assay normalized to GAPDH. We also studied growth inhibitory effects of the combination on KRAS mutant (mt) LGSOC patient-derived organoids. We performed next generation sequencing on archival samples from LGSOC patients treated with VS-6766 in combination with defactinib.Results: Signal transduction changes at 1 hr included reduction of p-FAK in 5/5 cell lines in response to defactinib. Cells exposed to VS-6766 showed a reduction in p-ERK and p-p90-RSK in 4/5 cell lines. Additionally, VS-6766 decreased p-cJUN and increased p-IκB in 4/5 cell lines, changes correlated with apoptosis. At 24 hrs, p-ERK and p-p90-RSK inhibition were maintained in 3/5 cell lines. Both drugs increased cleaved PARP in 4/5 cell lines and VS-6766 increased p-SMAD3 and BIM levels, indicating an increase in cell death/apoptosis. The combination of VS-6766 + defactinib showed synergistic growth inhibition in a KRAS mt LGSOC organoid model (combination index 0.51). The clinical combination of VS-6766 and defactinib (September 2021 cut-off) has shown an objective response rate (ORR) of 11/24 (46%) across all patients with LGSOC, and an ORR of 64% (7/11) for patients with KRAS mt LGSOC (n=11). In addition to mutations in KRAS, emerging data may suggest a correlation of U2AF1 and MED12 mutations with response.Conclusions: VS-6766, the dual RAF/MEK inhibitor, induces significant inhibition of ERK pathway signaling in addition to perturbations in TNF/NFκB signaling. Both defactinib and VS-6766 induce apoptosis in LGSOC models. The results provide mechanistic insights into the encouraging response rates observed in patients with LGSOC treated with VS-6766 and defactinib (NCT03875820). These data support the ongoing randomized phase II ENGOTov60/GOG3052/RAMP201 study (NCT04625270).Citation Format: Adam R. Stewart, Lisa Pickard, Ekta Paranjape, Victoria Sanchez Perez, Sanjib Chowdhury, Stephanie Lustgarten, Silvia Coma, Jonathan A. Pachter, Mark S. Carey, Gabriel DiMattia, Hannah C. Badham, Toby Prout, Mona Parmar, Muneeb Mahmud, Christina Yap, Matthew G. Krebs, Susana Banerjee, Udai Banerji. Mechanistic evaluation of VS-6766 (dual RAF/MEK inhibitor) and defactinib (FAK inhibitor) in low-grade serous ovarian cancer models with correlations to clinical response [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 3476

    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

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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