23,751 research outputs found

    Machine learning-guided directed evolution for protein engineering

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    Machine learning (ML)-guided directed evolution is a new paradigm for biological design that enables optimization of complex functions. ML methods use data to predict how sequence maps to function without requiring a detailed model of the underlying physics or biological pathways. To demonstrate ML-guided directed evolution, we introduce the steps required to build ML sequence-function models and use them to guide engineering, making recommendations at each stage. This review covers basic concepts relevant to using ML for protein engineering as well as the current literature and applications of this new engineering paradigm. ML methods accelerate directed evolution by learning from information contained in all measured variants and using that information to select sequences that are likely to be improved. We then provide two case studies that demonstrate the ML-guided directed evolution process. We also look to future opportunities where ML will enable discovery of new protein functions and uncover the relationship between protein sequence and function.Comment: Made significant revisions to focus on aspects most relevant to applying machine learning to speed up directed evolutio

    Optimization of the magnetic dynamo

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    In stars and planets, magnetic fields are believed to originate from the motion of electrically conducting fluids in their interior, through a process known as the dynamo mechanism. In this Letter, an optimization procedure is used to simultaneously address two fundamental questions of dynamo theory: "Which velocity field leads to the most magnetic energy growth?" and "How large does the velocity need to be relative to magnetic diffusion?" In general, this requires optimization over the full space of continuous solenoidal velocity fields possible within the geometry. Here the case of a periodic box is considered. Measuring the strength of the flow with the root-mean-square amplitude, an optimal velocity field is shown to exist, but without limitation on the strain rate, optimization is prone to divergence. Measuring the flow in terms of its associated dissipation leads to the identification of a single optimal at the critical magnetic Reynolds number necessary for a dynamo. This magnetic Reynolds number is found to be only 15% higher than that necessary for transient growth of the magnetic field.Comment: Optimal velocity field given approximate analytic form. 4 pages, 4 figure

    Event-based simulation of interference with alternatingly blocked particle sources

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    We analyze the predictions of an event-based corpuscular model for interference in the case of two-beam interference experiments in which the two sources are alternatingly blocked. We show that such experiments may be used to test specific predictions of the corpuscular model.Comment: FPP6 - Foundations of Probability and Physics 6, edited by A. Khrennikov et al., AIP Conference Proceeding

    Rocket- and aircraft-borne trace gas measurements in the winter polar stratosphere

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    In January and February 1987 stratospheric rocket- and aircraft-borne trace gas measurements were done in the North Polar region using ACIMS (Active Chemical Ionization Mass Spectrometry) and PACIMS (PAssive Chemical Ionization Mass Spectrometry) instruments. The rocket was launched at ESRANGE (European Sounding Rocket Launching Range) (68 N, 21 E, Northern Sweden) and the twin-jet research aircraft operated by the DFVLR (Deutsche Forschungs- und Versuchs-anstalt fuer Luft- und Raumfahrt), and equipped with a mass spectrometer laboratory was stationed at Kiruna airport. Various stratospheric trace gases were measured including nitric acid, sulfuric acid, non-methane hydrocarbons (acetone, hydrogen cyanide, acetonitrile, methanol etc.), and ambient cluster ions. The experimental data is presented and possible implications for polar stratospheric ozone discussed

    Engineered bidirectional communication mediates a consensus in a microbial biofilm consortium

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    Microbial consortia form when multiple species colocalize and communally generate a function that none is capable of alone. Consortia abound in nature, and their cooperative metabolic activities influence everything from biodiversity in the global food chain to human weight gain. Here, we present an engineered consortium in which the microbial members communicate with each other and exhibit a “consensus” gene expression response. Two colocalized populations of Escherichia coli converse bidirectionally by exchanging acyl-homoserine lactone signals. The consortium generates the gene-expression response if and only if both populations are present at sufficient cell densities. Because neither population can respond without the other's signal, this consensus function can be considered a logical AND gate in which the inputs are cell populations. The microbial consensus consortium operates in diverse growth modes, including in a biofilm, where it sustains its response for several days

    Magnetic permeability of near-critical 3d abelian Higgs model and duality

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    The three-dimensional abelian Higgs model has been argued to be dual to a scalar field theory with a global U(1) symmetry. We show that this duality, together with the scaling and universality hypotheses, implies a scaling law for the magnetic permeablity chi_m near the line of second order phase transition: chi_m ~ t^nu, where t is the deviation from the critical line and nu ~ 0.67 is a critical exponent of the O(2) universality class. We also show that exactly on the critical lines, the dependence of magnetic induction on external magnetic field is quadratic, with a proportionality coefficient depending only on the gauge coupling. These predictions provide a way for testing the duality conjecture on the lattice in the Coulomb phase and at the phase transion.Comment: 11 pages; updated references and small changes, published versio
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