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1.
bioRxiv ; 2021 Apr 09.
Article in English | MEDLINE | ID: mdl-33851158

ABSTRACT

The ongoing evolution of SARS-CoV-2 into more easily transmissible and infectious variants has sparked concern over the continued effectiveness of existing therapeutic antibodies and vaccines. Hence, together with increased genomic surveillance, methods to rapidly develop and assess effective interventions are critically needed. Here we report the discovery of SARS-CoV-2 neutralizing antibodies isolated from COVID-19 patients using a high-throughput platform. Antibodies were identified from unpaired donor B-cell and serum repertoires using yeast surface display, proteomics, and public light chain screening. Cryo-EM and functional characterization of the antibodies identified N3-1, an antibody that binds avidly (Kd,app = 68 pM) to the receptor binding domain (RBD) of the spike protein and robustly neutralizes the virus in vitro. This antibody likely binds all three RBDs of the trimeric spike protein with a single IgG. Importantly, N3-1 equivalently binds spike proteins from emerging SARS-CoV-2 variants of concern, neutralizes UK variant B.1.1.7, and binds SARS-CoV spike with nanomolar affinity. Taken together, the strategies described herein will prove broadly applicable in interrogating adaptive immunity and developing rapid response biological countermeasures to emerging pathogens.

2.
Science ; 356(6337): 508-513, 2017 05 05.
Article in English | MEDLINE | ID: mdl-28254783

ABSTRACT

Artificial intelligence has seen several breakthroughs in recent years, with games often serving as milestones. A common feature of these games is that players have perfect information. Poker, the quintessential game of imperfect information, is a long-standing challenge problem in artificial intelligence. We introduce DeepStack, an algorithm for imperfect-information settings. It combines recursive reasoning to handle information asymmetry, decomposition to focus computation on the relevant decision, and a form of intuition that is automatically learned from self-play using deep learning. In a study involving 44,000 hands of poker, DeepStack defeated, with statistical significance, professional poker players in heads-up no-limit Texas hold'em. The approach is theoretically sound and is shown to produce strategies that are more difficult to exploit than prior approaches.

3.
Science ; 347(6218): 145-9, 2015 Jan 09.
Article in English | MEDLINE | ID: mdl-25574016

ABSTRACT

Poker is a family of games that exhibit imperfect information, where players do not have full knowledge of past events. Whereas many perfect-information games have been solved (e.g., Connect Four and checkers), no nontrivial imperfect-information game played competitively by humans has previously been solved. Here, we announce that heads-up limit Texas hold'em is now essentially weakly solved. Furthermore, this computation formally proves the common wisdom that the dealer in the game holds a substantial advantage. This result was enabled by a new algorithm, CFR(+), which is capable of solving extensive-form games orders of magnitude larger than previously possible.

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