30 research outputs found

    Suspense-optimal college football play-offs

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    U.S. college football’s traditional bowl system, and lack of a postseason play-off tournament, has been controversial for years. The conventional wisdom is that a play-off would be a more fair way to determine the national champion, and more fun for fans to watch. The colleges finally agreed to begin a play-off in the 2014-2015 season, but with just four teams, and speculation continues that more teams will be added soon. A subtle downside to adding play-off teams is that it reduces the significance of regular season games.We use the framework of Ely, Frankel, and Kamenica (in press) to directly estimate the utility fans would get from this significance, that is, utility from suspense, under a range of play-off scenarios. Our results consistently indicate that play-off expansion causes a loss in regular season suspense utility greater than the gain in the postseason, implying the traditional bowl system (two team play-off) is suspense-optimal. We analyze and discuss implications for TV viewership and other contexts

    Learning from the Past, Looking to the Future: Modeling Social Unrest in Karachi, Pakistan

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    Social unrest represents a major challenge for policy makers around the globe, as it can quickly escalate from small scale disturbances to highly public protests, riots and even civil war. This research was motivated by a need to understand social instability and to unpack the comments made during a spring 2013 conference hosted by Pacific Northwest National Laboratory’s Center for Global Security and the U.S. Institute for Peace, where policymakers noted that models considering social instability are often not suitable for decision-making. This analysis shows that existing state level models of instability could be improved in spatial scale to the city level, even without significantly improved data access. Better data would make this analysis more complete and likely improve the quality of the model. Another challenge with incorporating modeling into decision-making is the need to understand uncertainty in a model. Policy makers are frequently tasked with making decisions without a clear outcome, so characterization of uncertainty is critical. This report describes the work and findings of the project. It took place in three phases: a literature review of social stability research, a “hindsight scan” that looked at historical data, and a “foresight scan” looking at future scenarios

    Technology and Research Requirements for Combating Human Trafficking: Enhancing Communication, Analysis, Reporting, and Information Sharing

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    DHS’ Science & Technology Directorate directed PNNL to conduct an exploratory study on the domain of human trafficking in the Pacific Northwest in order to examine and identify technology and research requirements for enhancing communication, analysis, reporting, and information sharing – activities that directly support efforts to track, identify, deter, and prosecute human trafficking – including identification of potential national threats from smuggling and trafficking networks. This effort was conducted under the Knowledge Management Technologies Portfolio as part of the Integrated Federal, State, and Local/Regional Information Sharing (RISC) and Collaboration Program

    Vol. 2 Ch. 4 Material Choice and Interaction on Brown\u27s Bottom

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    https://ideaexchange.uakron.edu/encountering_hopewell/1014/thumbnail.jp

    Utility of Social Modeling in Assessment of a State’s Propensity for Nuclear Proliferation

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    This report is the third and final report out of a set of three reports documenting research for the U.S. Department of Energy (DOE) National Security Administration (NASA) Office of Nonproliferation Research and Development NA-22 Simulations, Algorithms, and Modeling program that investigates how social modeling can be used to improve proliferation assessment for informing nuclear security, policy, safeguards, design of nuclear systems and research decisions. Social modeling has not to have been used to any significant extent in a proliferation studies. This report focuses on the utility of social modeling as applied to the assessment of a State's propensity to develop a nuclear weapons program

    Covalent targeting of remote cysteine residues to develop CDK12 and CDK13 inhibitors

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    Cyclin-dependent kinases 12 and 13 (CDK12 and CDK13) play critical roles in the regulation of gene transcription. However, the absence of CDK12 and CDK13 inhibitors has hindered the ability to investigate the consequences of their inhibition in healthy cells and cancer cells. Here we describe the rational design of a first-in-class CDK12 and CDK13 covalent inhibitor, THZ531. Co-crystallization of THZ531 with CDK12–cyclin K indicates that THZ531 irreversibly targets a cysteine located outside the kinase domain. THZ531 causes a loss of gene expression with concurrent loss of elongating and hyperphosphorylated RNA polymerase II. In particular, THZ531 substantially decreases the expression of DNA damage response genes and key super-enhancer-associated transcription factor genes. Coincident with transcriptional perturbation, THZ531 dramatically induced apoptotic cell death. Small molecules capable of specifically targeting CDK12 and CDK13 may thus help identify cancer subtypes that are particularly dependent on their kinase activities.United States. National Institutes of Health (HG002668)United States. National Institutes of Health (CA109901

    Covalent targeting of remote cysteine residues to develop CDK12 and CDK13 inhibitors

    Get PDF
    Cyclin-dependent kinases 12 and 13 (CDK12 and CDK13) play critical roles in the regulation of gene transcription. However, the absence of CDK12 and CDK13 inhibitors has hindered the ability to investigate the consequences of their inhibition in healthy cells and cancer cells. Here we describe the rational design of a first-in-class CDK12 and CDK13 covalent inhibitor, THZ531. Co-crystallization of THZ531 with CDK12–cyclin K indicates that THZ531 irreversibly targets a cysteine located outside the kinase domain. THZ531 causes a loss of gene expression with concurrent loss of elongating and hyperphosphorylated RNA polymerase II. In particular, THZ531 substantially decreases the expression of DNA damage response genes and key super-enhancer-associated transcription factor genes. Coincident with transcriptional perturbation, THZ531 dramatically induced apoptotic cell death. Small molecules capable of specifically targeting CDK12 and CDK13 may thus help identify cancer subtypes that are particularly dependent on their kinase activities.United States. National Institutes of Health (HG002668)United States. National Institutes of Health (CA109901
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