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Conventional computing architectures have no known efficient algorithms for combinatorial optimization tasks such as the Ising problem, which requires finding the ground state spin configuration of an arbitrary Ising graph. Physical Ising machines have recently been developed as an alternative to conventional exact and heuristic solvers; however, these machines typically suffer from decreased ground state convergence probability or universality for high edge-density graphs or arbitrary graph weights, respectively. We experimentally demonstrate a proof-of-principle integrated nanophotonic recurrent Ising sampler (INPRIS), using a hybrid scheme combining electronics and silicon-on-insulator photonics, that is capable of converging to the ground state of various four-spin graphs with high probability. The INPRIS results indicate that noise may be used as a resource to speed up the ground state search and to explore larger regions of the phase space, thus allowing one to probe noise-dependent physical observables. Since the recurrent photonic transformation that our machine imparts is a fixed function of the graph problem and therefore compatible with optoelectronic architectures that support GHz clock rates (such as passive or non-volatile photonic circuits that do not require reprogramming at each iteration), this work suggests the potential for future systems that could achieve orders-of-magnitude speedups in exploring the solution space of combinatorially hard problems. 

Abstract Organophosphate nerve agents rapidly inhibit cholinesterases thereby destroying the ability to sustain life. Strong nucleophiles, such as oximes, have been used as therapeutic reactivators of cholinesterase‐organophosphate complexes, but suffer from short half‐lives and limited efficacy across the broad spectrum of organophosphate nerve agents. Cholinesterases have been used as long‐lived therapeutic bioscavengers for unreacted organophosphates with limited success because they react with organophosphate nerve agents with one‐to‐one stoichiometries. The chemical power of nucleophilic reactivators is coupled to long‐lived bioscavengers by designing and synthesizing cholinesterase‐polymer‐oxime conjugates using atom transfer radical polymerization and azide‐alkyne “click” chemistry. Detailed kinetic studies show that butyrylcholinesterase‐polymer‐oxime activity is dependent on the electrostatic properties of the polymers and the amount of oxime within the conjugate. The covalent coupling of oxime‐containing polymers to the surface of butyrylcholinesterase slows the rate of inactivation of paraoxon, a model nerve agent. Furthermore, when the enzyme is covalently inhibited by paraoxon, the covalently attached oxime induced inter‐ and intramolecular reactivation. Intramolecular reactivation will open the door to the generation of a new class of nerve agent scavengers that couple the speed and selectivity of biology to the ruggedness and simplicity of synthetic chemicals.