5,325 research outputs found

    Providence College Faculty Author Series 2018-2019: Jeffrey Johnson

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    In this installment of the Faculty Authors Series, Jeffrey Johnson (History, Providence College) discusses his newest book, The 1916 Preparedness Day Bombing: Anarchy and Terrorism in Progressive Era America

    Providence College Faculty Author Series 2018-2019: Jeffrey Johnson

    No full text
    In this installment of the Faculty Authors Series, Jeffrey Johnson (History, Providence College) discusses his newest book, The 1916 Preparedness Day Bombing: Anarchy and Terrorism in Progressive Era America

    EWS-­FLI1 as a molecular target: Small molecule inhibitors for a disordered protein

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    Ph.D.Ewing sarcoma family of tumors (ESFT) consists of highly malignant tumors of the bone and soft tissue. Ninety-five percent of cases contain a balanced t(11;22) or t(21;22) rearrangement, combining the amino-terminus of EWS to the carboxy-terminus of FLI1 or ERG, which contain the highly conserved ets DNA binding domain. As the EWS-FLI1 protein is found only in ESFT cells and its expression is required for the oncogenic phenotype, it presents a promising molecular target for anti-cancer therapies. EWS-FLI1 is a hydrophobic disordered protein with unknown three-dimensional structure, precluding standard structure-based drug design. RNA Helicase A (RHA) enhances EWS-FLI1 driven oncogenesis and interruption of this protein-protein complex validates this interaction as a unique therapeutic target. Surface plasmon resonance screening identified compounds that bind to EWS-FLI1, including a lead compound that induces apoptosis in ESFT cells and reduces the growth of xenografts. Our compound, YK-4-279, has a chiral center and can be separated into enantiomers, only one of which is able to specifically target the protein-protein interaction. This work is significant for its identification of a single enantiomer effect upon a protein-protein interaction suggesting that small molecule targeting of intrinsically disordered proteins can be highly specific. Given the challenges of drug design targeted to EWS-FLI1, we proposed that characterization of the physical interaction points between EWS-FLI1 and RHA would allow us to better alter the lead compound to block this protein-protein interaction. While full length EWS-FLI1 is able to pull down RHA, fragments of the protein are not. Although we can successfully crosslink EWS-FLI1 and RHA, we have yet to identify what region of EWS-FLI1 is involved. We are able to show specific regions of order and disorder of EWS-FLI1, which may lead to the identification of the binding site for YK-4-279. The development of higher-throughput methods for testing small molecules that bind to or inhibit EWS-FLI1 function will allow us to further investigate protein structure and function. These data are a contribution to the future development of small molecules in an era where novel approaches to cancer therapy are critical for improving patient care

    Dr. Jeffrey Hass – Faculty Author Interview

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    Dr. Jeffrey Hass, Associate Professor of Sociology, discusses his new book, Power, Culture, and Economic Change in Russia: To the Undiscovered Country of Post-Socialism, 1988-2008. Utilizing cutting-edge theory and unique data, this book examines the role of power, culture, and practice in Russia’s story of post-socialist economic change, and provides a framework for addressing general economic change

    Cassette Exon RNA Splicing Altered in Ewing Sarcoma Is Characterized by Higher Guanine-Cytosine Content and Lower Splice Site Strength Indicative of Intron-Definition Splicing

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    Ph.D.Ewing sarcoma (EwS) is a pediatric cancer that typically presents at a mean of 15 years of age and is the second most common bone tumor in children and adolescents. While there have been substantial investigations into the mechanism of EwS oncogenesis, few of these findings have translated to improved therapeutics, and treatment of EwS has largely remained static for the last 30 years. Patients that present with localized EwS have an approximately 70% 5-year survival rate whereas patients that present with metastatic EwS have only a 30% 5-year survival rate. New approaches to understanding the oncogenic process and potential vulnerabilities behind EwS are badly needed, as targeted therapeutics for EwS patients have the opportunity to drastically improve long-term outcomes and reduce systemic effects. In this dissertation I present first the creation of a model to study EwS using bone marrow-derived human mesenchymal stem cells (hMSC-BM), as the lack of patient samples presents a substantial barrier to EwS research. I then describe my efforts to create a reference transcriptome using long-read sequencing that is more comprehensive than commonly used reference transcriptomes. I use this transcriptome to quantify mRNA splicing in tumor samples, followed by a detailed analysis of sequence features associated with altered RNA splicing in EwS

    Books piece on a reading by Jeffrey Lent, author of Lost Nation, that will b

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    Books piece on a reading by Jeffrey Lent, author of Lost Nation, that will be presented at the Portland Public Library July 31

    University of Texas at Arlington (U. T. A.) President Spaniolo with author Jeffrey Toobin

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    University of Texas at Arlington (U. T. A.) President Spaniolo with author Jeffrey Toobin, legal analyst for The New Yorker, 03/2010https://mavmatrix.uta.edu/specialcollections_spaniolomaterials/1038/thumbnail.jp

    An Ethnographer in Poland: On Experience as a Mode of Engaging Jewishness

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    Museums have become especially prominent sites of Jewish experience—not only in Poland but elsewhere, including cities with large Jewish populations—as permanent and very publicly visible institutions. Their presence looms large despite the fact that many, if not most, people will visit a given museum only once, spending an hour or two there. Given its scope and salience, the POLIN Museum of the History of Polish Jews is poised to become the keystone in the arch of Polish Jewish experience

    Enacting Ethnicity: Yiddishkeit Masked and Unmasked on the Contemporary American Stage

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    Two recent productions of American dramas employed provocative strategies for enacting Jewish ethnicity: National Asian American Theatre Company’s performance of Clifford Odets’s Awake and Sing! with an all-Asian American cast and New Yiddish Rep’s staging of Toyt fun a seylsman, a Yiddish translation of Arthur Miller’s Death of a Salesman. Each production entails a different approach to performing Jewishness that exemplifies these companies’ respective artistic agendas regarding the enactment of ethnicity, resulting in complex performances of masking and unmasking Jewishness. Moreover, their analysis illuminates how ethnicity is conceptualized and realized in the United States in the early decades of the twenty-first century. Yiddish appears strategically, if often obliquely, in the histories of composition, production, and reception for both dramas, emblematic of shifting notions of enacting ethnicity.Peer reviewe

    New Insights into Materialism and Conspicuous Consumption in China

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    This paper provides insights based on recent literature and findings that relate to materialism and conspicuous consumption among Chinese consumers. There is a specific focus on gender related issues and implications on consumer well-being. Our work is intended to assist in both conceptual and hypothesis development for other interested scholars.Peer reviewe
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