2,324 research outputs found

    Perspectives on the COVID-19 Pandemic: Truth and Trust

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    When one examines life in various countries of the world regardless of type of government, health system, or even culture, one sees the great diversity of the world but also large areas of commonality among all people and all places.  The twentieth century’s history is one of almost constant war, two of those wars having affected the majority of the global population, but only one event parallels today’s pandemic in impact on almost every individual on planet Earth: the great pandemic of 1918, which by various accounts took between 20 to 100 million lives over a three-year period

    Sweat, Cigs and A Ball of Noise

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    Corduroy Jones is contacted by a local promoter to reunite his band Streetwise Preacher. Over a three week span, Corduroy and his bandmates Tony and Johnny go through a series of events leading up to their Halloween Night reunion show

    How party polarization makes the legislative process even slower when government is divided

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    Since 2010, the U.S. has experienced divided government, with the Democrats holding the White House, and The Republican Party controlling the House of Representatives, and since January, the Senate. In new research which analyses the passage of 2,200 bills from 1949 to 2010, Tyler Hughes and Deven Carlson find that divided government slows down the legislative process by 60 days, on average. This delay is made even worse when the level of party polarization is higher, which makes partisan compromises even more difficult

    Modeling reactivity to biological macromolecules with a deep multitask network

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    Most small-molecule drug candidates fail before entering the market, frequently because of unexpected toxicity. Often, toxicity is detected only late in drug development, because many types of toxicities, especially idiosyncratic adverse drug reactions (IADRs), are particularly hard to predict and detect. Moreover, drug-induced liver injury (DILI) is the most frequent reason drugs are withdrawn from the market and causes 50% of acute liver failure cases in the United States. A common mechanism often underlies many types of drug toxicities, including both DILI and IADRs. Drugs are bioactivated by drug-metabolizing enzymes into reactive metabolites, which then conjugate to sites in proteins or DNA to form adducts. DNA adducts are often mutagenic and may alter the reading and copying of genes and their regulatory elements, causing gene dysregulation and even triggering cancer. Similarly, protein adducts can disrupt their normal biological functions and induce harmful immune responses. Unfortunately, reactive metabolites are not reliably detected by experiments, and it is also expensive to test drug candidates for potential to form DNA or protein adducts during the early stages of drug development. In contrast, computational methods have the potential to quickly screen for covalent binding potential, thereby flagging problematic molecules and reducing the total number of necessary experiments. Here, we train a deep convolution neural networkthe XenoSite reactivity modelusing literature data to accurately predict both sites and probability of reactivity for molecules with glutathione, cyanide, protein, and DNA. On the site level, cross-validated predictions had area under the curve (AUC) performances of 89.8% for DNA and 94.4% for protein. Furthermore, the model separated molecules electrophilically reactive with DNA and protein from nonreactive molecules with cross-validated AUC performances of 78.7% and 79.8%, respectively. On both the site- and molecule-level, the model’s performances significantly outperformed reactivity indices derived from quantum simulations that are reported in the literature. Moreover, we developed and applied a selectivity score to assess preferential reactions with the macromolecules as opposed to the common screening traps. For the entire data set of 2803 molecules, this approach yielded totals of 257 (9.2%) and 227 (8.1%) molecules predicted to be reactive only with DNA and protein, respectively, and hence those that would be missed by standard reactivity screening experiments. Site of reactivity data is an underutilized resource that can be used to not only predict if molecules are reactive, but also show where they might be modified to reduce toxicity while retaining efficacy. The XenoSite reactivity model is available at http://swami.wustl.edu/xenosite/p/reactivity

    Privacy-preserving scoring of tree ensembles : a novel framework for AI in healthcare

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    Machine Learning (ML) techniques now impact a wide variety of domains. Highly regulated industries such as healthcare and finance have stringent compliance and data governance policies around data sharing. Advances in secure multiparty computation (SMC) for privacy-preserving machine learning (PPML) can help transform these regulated industries by allowing ML computations over encrypted data with personally identifiable information (PII). Yet very little of SMC-based PPML has been put into practice so far. In this paper we present the very first framework for privacy-preserving classification of tree ensembles with application in healthcare. We first describe the underlying cryptographic protocols that enable a healthcare organization to send encrypted data securely to a ML scoring service and obtain encrypted class labels without the scoring service actually seeing that input in the clear. We then describe the deployment challenges we solved to integrate these protocols in a cloud based scalable risk-prediction platform with multiple ML models for healthcare AI. Included are system internals, and evaluations of our deployment for supporting physicians to drive better clinical outcomes in an accurate, scalable, and provably secure manner. To the best of our knowledge, this is the first such applied framework with SMC-based privacy-preserving machine learning for healthcare
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