Search

Technical challenges remain in the sequencing of RNA viruses due to their high intra-host diversity. This bottleneck is particularly pronounced when interrogating long-range co-evolved genetic interactions given the read-length limitations of next-generation sequencing platforms. This has hampered the direct observation of these genetic interactions that code for protein-protein interfaces with relevance in both drug and vaccine development. Here we overcome these technical limitations by developing a nanopore-based long-range viral sequencing pipeline that yields accurate single molecule sequences of circulating virions from clinical samples. We demonstrate its utility in observing the evolution of individual HIV Gag-Pol genomes in response to antiviral pressure. Our pipeline, called Multi-read Hairpin Mediated Error-correction Reaction (MrHAMER), yields >1000s of viral genomes per sample at 99.9% accuracy, maintains the original proportion of sequenced virions present in a complex mixture, and allows the detection of rare viral genomes with their associated mutations present at

PURPOSE Opioid prescribing trends in medical oncology are poorly defined past 2017, the year after the CDC updated opioid prescription guidelines in noncancer settings. We aim to characterize pain management by medical oncologists by analyzing opioid and gabapentin prescribing trends from 2013 to 2019, identify physician-related factors associated with prescribing patterns, and assess whether CDC guidelines for nononcologic settings changed prescribing patterns. METHODS The Centers for Medicare & Medicaid Services (CMS) Medicare Part D Prescribers--by Provider, CMS Medicare Part D Prescribers--by Provider and Drug, and CMS Medicare Physician National Downloadable files from 2013 to 2019 were merged by National Provider Identification. The database included physicians' sex, years of practice, regions, and practice settings. Multivariable binary logistic regression identified significant predictors of total opioid, longacting opioid, and gabapentin prescriptions. RESULTS Binary logistic regression modeling revealed no significant difference in mean daily total opioid prescriptions from 2013 to 2017. Daily opioid prescriptions by medical oncologists decreased significantly after 2017 (P < .001). Increased opioid prescribing was associated with physician male sex (P < .001), practicing over 10 years (P < .001), and practice in nonurban areas (P < .001). Opioid prescribing was greatest in the South and Midwest United States (P < .001). The same patterns were observed with total longacting opioid prescriptions, whereas gabapentin prescribing increased from 2013 to 2019 (P < .001). CONCLUSION Opioid prescriptions by medical oncologists decreased significantly from 2013 to 2019, but this decrease was most substantial from 2017 to 2019. These results may imply that the 2016 CDC guidelines influenced medical oncologists, particularly more junior physicians in urban settings, to manage chronic cancer pain with alternative therapies. [ABSTRACT FROM AUTHOR]

Recent studies suggest that research participants show reduced distortion of their taboo attitudes and behaviors when they take part in Internet-based procedures from outside the laboratory. We explored whether such procedures would reduce distortion in the assessment of racial bias. In Study 1, White participants who completed the study in the laboratory evaluated Black targets more favorably than White targets. This unexpected 'outgroupfavoring' pattern occurred in both pencil-and-paper and Internet versions of the study, showing that modality did not produce it; but when participants worked outside the laboratory via the Internet, this pattern disappeared. Study 2 replicated the above findings and further indicated that the reduced distortion in Internet-based studies was due to the removal of the experimenter rather than removing the participants from the laboratory environment. The implications of these findings for the study of controlled processes of prejudice and the nature of Internet-based social communication are discussed. Keywords: social desirability distortion; controlled processes; Internet research; racism; reverse racism

A 30 year-old PuF4 sample consisting of brown powder (PuF4-b) and pink granules (PuF4-p) was analyzed. X-ray diffraction shows the bulk is comprised of three compounds: PuF4, PuO2, and PuF4·1.6H2O. Broadening of PuF4 XRD peaks suggests possible α -damage. After annealing at 650 °C, crystalline PuF4 and PuO2 remain. Thermogravimetric analysis and differential scanning calorimetry—with simultaneous evolved gas analysis—of the separated PuF4-p and PuF4-b components reveal a distinct sequence of reactions. Dehydration occurs between ~ 90 and 300 °C. Exothermic annealing of the α -damage occurs in two stages: at 350–355 °C and at 555–558 °C. Hydrofluoric acid, fluorine and helium desorb during the first exotherm. Above 700 °C, PuF4 reacts with PuO2, resulting in oxygen release and mass loss. [ABSTRACT FROM AUTHOR]

Cyber-physical systems (CPS) enable unprecedented communication between product designers and manufacturers. Effective use of these technologies both enables and requires a new paradigm of methods and models to identify the most profitable and environmentally friendly production plans for a manufacturing network. The operating system for cyber-physical manufacturing (OSCM) and the paired network operations administration and monitoring (NOAM) software are introduced. These technologies guide our development of a mixed integer bilevel programming (BP) model that models the hierarchy between designers and manufacturers as a Stackelberg game while considering multiple objectives for each of them. Designers select and pay manufacturers, while manufacturers decide how to execute the order with the payment provided by the designer. To solve the model, a tailored solution method combining a decomposition-based approach with approximation of the lower level Pareto-optimal solution set is proposed. The model is applied to a case study based on a network of manufacturers in Wisconsin and Illinois. With the proposed model, designers and manufacturers alike can take full advantage of CPS to increase profits and decrease environmental impacts. [ABSTRACT FROM AUTHOR]

The water footprint of energy systems must be considered, as future water scarcity has been identified as a major concern. This work presents a general life cycle network modeling and optimization framework for energy-based products and processes using a functional unit of liters of water consumed in the processing pathway. We analyze and optimize the water-energy nexus over the objectives of water footprint minimization, maximization of economic output per liter of water consumed (economic efficiency of water), and maximization of energy output per liter of water consumed (energy efficiency of water). A mixed integer, multiobjective nonlinear fractional programming (MINLFP) model is formulated. A mixed integer linear programing (MILP)-based branch and refine algorithm that incorporates both the parametric algorithm and nonlinear programming (NLP) subproblems is developed to boost solving efficiency. A case study in bioenergy is presented, and the water footprint is considered from biomass cultivation to biofuel production, providing a novel perspective into the consumption of water throughout the value chain. The case study, optimized successively over the three aforementioned objectives, utilizes a variety of candidate biomass feedstocks to meet primary fuel products demand (ethanol, diesel, and gasoline). A minimum water footprint of 55.1 ML/year was found, economic efficiencies of water range from -$1.31/L to $0.76/L, and energy efficiencies of water ranged from 15.32 MJ/L to 27.98 MJ/L. These results show optimization provides avenues for process improvement, as reported values for the energy efficiency of bioethanol range from 0.62 MJ/L to 3.18 MJ/L. Furthermore, the proposed solution approach was shown to be an order of magnitude more efficient than directly solving the original MINLFP problem with general purpose solvers. [ABSTRACT FROM AUTHOR]

A comprehensive optimization model that can determine the most cost-effective and environmentally sustainable production pathways in an integrated processing network is needed, especially in the bioconversion space. We develop the most comprehensive bioconversion network to date with 193 technologies and 129 materials/compounds for fuels production. We consider the tradeoff between scaling capital and operating expenditures (CAPEX and OPEX) as well as life cycle environmental impacts. Additionally, we develop a general network-based modeling framework with nonconvex terms for CAPEX. To globally optimize the nonlinear program with high computational efficiency, we develop a specialized branch-and-refine algorithm based on successive piecewise linear approximations. Two case studies are considered. The optimal pathways have profits from −$12.9 to $99.2M/yr, and emit 791 ton CO2-eq/yr to 31,571 ton CO2-eq/yr. Utilized technologies vary from corn-based fermentation to pyrolysis. The proposed algorithm reduces computational time by up to three orders of magnitude compared to general-purpose global optimizers. © 2014 American Institute of Chemical Engineers AIChE J, 61: 530-554, 2015 [ABSTRACT FROM AUTHOR]

A 30 year-old PuF4 sample consisting of brown powder (PuF4-b) and pink granules (PuF4-p) was analyzed. X-ray diffraction shows the bulk is comprised of three compounds: PuF4, PuO2, and PuF4·1.6H2O. Broadening of PuF4 XRD peaks suggests possible α -damage. After annealing at 650 °C, crystalline PuF4 and PuO2 remain. Thermogravimetric analysis and differential scanning calorimetry—with simultaneous evolved gas analysis—of the separated PuF4-p and PuF4-b components reveal a distinct sequence of reactions. Dehydration occurs between ~ 90 and 300 °C. Exothermic annealing of the α -damage occurs in two stages: at 350–355 °C and at 555–558 °C. Hydrofluoric acid, fluorine and helium desorb during the first exotherm. Above 700 °C, PuF4 reacts with PuO2, resulting in oxygen release and mass loss. [ABSTRACT FROM AUTHOR]