We developed a de novo protein design strategy to swiftly engineer decoys for neutralizing pathogens that exploit extracellular host proteins to infect the cell. Our pipeline allowed the design, validation, and optimization of de novo hACE2 decoys to neutralize SARS-CoV-2. The best decoy, CTC-445.2, binds with low nanomolar affinity and high specificity to the RBD of the spike protein. Cryo-EM shows that the design is accurate and can simultaneously bind to all three RBDs of a single spike protein. Because the decoy replicates the spike protein target interface in hACE2, it is intrinsically resilient to viral mutational escape. A bivalent decoy, CTC-445.2d, shows ~10-fold improvement in binding. CTC-445.2d potently neutralizes SARS-CoV-2 infection of cells in vitro and a single intranasal prophylactic dose of decoy protected Syrian hamsters from a subsequent lethal SARS-CoV-2 challenge.
Printed on paper containing at least 50% wastepaper, including 10% post consumer waste.iii
ForewordThe purpose of this techno-economic analysis is to compare a set of biofuel conversion technologies selected for their promise and near-term technical viability. Every effort is made to make this comparison on an equivalent basis using common assumptions. The process design and parameter value choices underlying this analysis are based on public domain literature only. For these reasons, these results are not indicative of potential performance, but are meant to represent the most likely performance given the current state of public knowledge.
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Executive SummaryThis study compares capital and production costs of two biomass-to-liquid production plants based on gasification. The goal is to produce liquid transportation fuels via Fischer-Tropsch synthesis with electricity as a co-product. The biorefineries are fed by 2,000 metric tons per day of corn stover. The first biorefinery scenario is an oxygen-fed, low-temperature (870°C), nonslagging, fluidized bed gasifier. The second scenario is an oxygen-fed, high-temperature (1,300°C), slagging, entrained flow gasifier. Both are followed by catalytic Fischer-Tropsch synthesis and hydroprocessing to naphtha-range (gasoline blend stock) and distillate-range (diesel blend stock) liquid fractions. (Hydroprocessing is a set of refinery processes that removes impurities and breaks down large molecules to fractions suitable for use in commercial formulations.)Process modeling software (Aspen Plus) is utilized to organize the mass and energy streams and cost estimation software is used to generate equipment costs. Economic analysis is performed to estimate the capital investment and operating costs. A 20-year discounted cash flow rate of return analysis is developed to estimate a fuel product value (PV) at a net present value of zero with 10% internal rate of return. All costs are adjusted to the year 2007. The technology is limited to commercial technology available for implementation in the next 5-8 years, and as a result, the process design is restricted to available rather than projected data.Results show that the total capital investment required for n th plant scenarios is $610 million and $500 million for high-temperature and low-temperature scenarios, respectively. PV for the hightemperature and low-temperature scenarios is estimated to be $4.30 and $4.80 per gallon of gasoline equivalent (GGE), respectively, based on a feedstock cost of $75 per dry short ton. The main reason for a difference in PV between the scenarios is because of a higher carbon efficiency and subsequent higher fuel yield for the high-temperature scenario. Sensitivity analysis is also performed on process and economic parameters. This analysis shows that total capital investment and feedstock cost are among the most influential parameters affecting the PV, while least influential parameters include per-pass Fischer-Tropsch-reaction-conversion extent, inlet feedstock moisture, and ...
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