1,725,147 research outputs found
Block Card 4827 Thobe Road
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: Dwelling | 4827 Thobe Road (Toledo, Ohio) | attached garage | Ranch houses | Edgewood Addition (Toledo, Ohio) | Reynolds Corners Area (Toledo, Ohio
Block Card 4827 Rambo Lane
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: Dwelling | 4827 Rambo Lane (Toledo, Ohio) | Ranch houses | Monroe Acres (Toledo, Ohio) | Franklin Park Area (Toledo, Ohio) | West Toledo Area (Toledo, Ohio
Poly (ADP-Ribose) polymerase inhibitor MK-4827 together with radiation as a novel therapy for metastatic neuroblastoma
Get PDFTo assess poly (ADP-ribose) polymerase (PARP) inhibitor MK-4827 together with radiation for the treatment of neuroblastoma. Clonogenic survival assays were used to assess MK-4827, radiation and combination thereof in four neuroblastoma cell lines. In vivo efficacy was tested in a murine xenograft model of metastatic neuroblastoma. In vivo targeted inhibition and biological effects included measurement of cleaved caspase-3, γ-H2AX, and Ki 67 by immunohistochemistry (IHC) and poly-ADP-ribose by Enzyme-Linked Immunosorbent Assay. Treatment of neuroblastoma cell lines reduced clonogenicity and resulted in additive effects with radiation. In vivo treatment with MK-4827 and radiation prolonged survival (p <0.01) compared to single modalities. In vivo superiority of MK-4827 plus radiation was further documented by significant elevations of cleaved caspase-3 and γ-H2AX in tumors from the combination group compared to single modality cohorts. Combination of MK-4827 and radiation might provide effective therapy for children with high-risk neuroblastom
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
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe 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
Abstract 685: PARP inhibitor MK-4827 is synthetic lethal for tumors with homologous recombination defects associated with ATM-deficiency, PTEN-deletion and microsatellite instability (MSI)
No full textAbstract
Poly(ADP-ribose) polymerase (PARP) −1 and −2 enzymes play a critical role in the base excision DNA repair (BER) pathway. PARP inhibition in oncology has the potential to target pre-defined sub-populations with higher sensitivity and to widen the therapeutic index of chemotherapy and radiotherapy. Pre-clinical and clinical evidence demonstrated that PARP inhibitors are synthetic lethal for tumors with defects in the homologous recombination (HR) pathway, such as tumors with mutations in the BRCA1 or BRCA2 genes.
MK-4827 is a potent and selective orally available PARP-1/2 inhibitor currently in Phase 1 development. In pre-clinical models, MK-4827 displays excellent monotherapy activity in a large panel of BRCA mutant cell lines (10 nM ≤ CC50 ≤ 90nM) with at least 10-fold selectivity over BRCA wild-type celllines (CC50 ≥ 1.5 uM). We have explored the potential of MK-4827 for the therapy of tumors with defects in the HR pathway in addition to mutation in the BRCA genes.
In this study we have evaluated the activity of MK-4827 on tumor cell lines with defects in the homologous recombination pathway as a consequence of 1) inactivation of ATM gene in melanoma and mantle cell lymphoma cell lines; 2) PTEN gene deletion in prostate cancer cells; 3) MRE11 expression level defects associated with the Microsatellite Instability (MSI) phenotype in colorectal cancer cells (CRCs).
We demonstrated that cancer cells with an inactive ATM pathway as a consequence of homozygous ATM gene inactivation are very sensitive to MK-4827 inhibition (CC50 ≤ 50nM). MK-4827 also displays strong activity in ATM-deficient xenograft models. Heterozygous ATM inactivation is not sufficient to confer sensitivity to MK-4827.
Our studies also showed that prostate cancer cells with homozygous-deletion of PTEN gene are sensitive to MK-4827 inhibition (100nM ≤ CC50 ≤ 600nM) as measured by long-term cell growth and proliferation assays. Homozygous, but not heterozygous, PTEN-deletion is required for MK-4827 sensitivity in agreement with data available for sensitivity of BRCA- and ATM-deficient cells to MK-4827.
Finally, we have screened a panel of CRC cells with known Microsatellite Instability and have observed that MSI+ cells are sensitive to MK-4827 in long term proliferation assays, in contrast to Microsatellite stable (MSS) CRC cells which are resistant. In agreement with previous reports, we observed that MSI+ CRC cells show low expression levels of MRE11, a key protein for homologous recombination.
Conclusion: Our pre-clinical data demonstrate that MK-4827 is synthetic lethal for tumors with ATM-deficiency, PTEN-deletion or MSI+ instability and suggest that patients with tumors carrying these genetic defects might benefit from treatment with PARP inhibitors
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 685.</jats:p
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe 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
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