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1.
Nat Commun ; 15(1): 4229, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38762499

RESUMO

Squeezed states of light have been used extensively to increase the precision of measurements, from the detection of gravitational waves to the search for dark matter. In the optical domain, high levels of vacuum noise squeezing are possible due to the availability of low loss optical components and high-performance squeezers. At microwave frequencies, however, limitations of the squeezing devices and the high insertion loss of microwave components make squeezing vacuum noise an exceptionally difficult task. Here we demonstrate direct measurements of high levels of microwave squeezing. We use an ultra-low loss setup and weakly-nonlinear kinetic inductance parametric amplifiers to squeeze microwave noise 7.8(2) dB below the vacuum level. The amplifiers exhibit a resilience to magnetic fields and permit the demonstration of large squeezing levels inside fields of up to 2 T. Finally, we exploit the high critical temperature of our amplifiers to squeeze a warm thermal environment, achieving vacuum level noise at a temperature of 1.8 K. These results enable experiments that combine squeezing with magnetic fields and permit quantum-limited microwave measurements at elevated temperatures, significantly reducing the complexity and cost of the cryogenic systems required for such experiments.

2.
Sci Adv ; 7(33)2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34389538

RESUMO

Spin-based silicon quantum electronic circuits offer a scalable platform for quantum computation, combining the manufacturability of semiconductor devices with the long coherence times afforded by spins in silicon. Advancing from current few-qubit devices to silicon quantum processors with upward of a million qubits, as required for fault-tolerant operation, presents several unique challenges, one of the most demanding being the ability to deliver microwave signals for large-scale qubit control. Here, we demonstrate a potential solution to this problem by using a three-dimensional dielectric resonator to broadcast a global microwave signal across a quantum nanoelectronic circuit. Critically, this technique uses only a single microwave source and is capable of delivering control signals to millions of qubits simultaneously. We show that the global field can be used to perform spin resonance of single electrons confined in a silicon double quantum dot device, establishing the feasibility of this approach for scalable spin qubit control.

4.
Eur J Med Chem ; 45(11): 5309-17, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20850205

RESUMO

The tertiary structure of the Leu308Val mutant of human 20α-hydroxysteroid dehydrogenase (AKR1C1) in complex with the inhibitor 3,5-dichlorosalicylic acid (DCL) has been determined. Structures and kinetic properties of the wild-type and mutant enzymes indicate that Leu308 is a selectivity determinant for inhibitor binding. The Leu308Val mutation resulted in 13-fold and 3-fold reductions in the inhibitory potencies of DCL and 3-bromo-5-phenylsalicylic acid (BPSA), respectively. The replacement of Leu308 with an alanine resulted in 473-fold and 27-fold reductions in the potencies for DCL and BPSA, respectively. In our attempts to optimize inhibitor potency and selectivity we synthesized 5-substituted 3-chlorosalicylic acid derivatives, of which the most potent compound, 3-chloro-5-phenylsalicylic acid (K(i) = 0.86 nM), was 24-fold more selective for AKR1C1 relative to the structurally similar 3α-hydroxysteroid dehydrogenase (AKR1C2). Furthermore, the compound inhibited the metabolism of progesterone in AKR1C1-overexpressed cells with an IC(50) value equal to 100 nM.


Assuntos
20-Hidroxiesteroide Desidrogenases/antagonistas & inibidores , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Ácido Salicílico/química , Ácido Salicílico/farmacologia , 20-Hidroxiesteroide Desidrogenases/genética , Animais , Bovinos , Células Cultivadas , Cristalização , Humanos , Concentração Inibidora 50 , Cinética , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Estrutura Molecular , Mutagênese Sítio-Dirigida , Proteínas Recombinantes/antagonistas & inibidores , Proteínas Recombinantes/genética , Espectrometria de Massas por Ionização por Electrospray , Relação Estrutura-Atividade
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