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- Menden, MP, et al.
(författare)
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Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2674-
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Tidskriftsartikel (refereegranskat)abstract
- The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
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| 2. |
- Gut, C., et al.
(författare)
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Stationary optomechanical entanglement between a mechanical oscillator and its measurement apparatus
- 2020
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Ingår i: PHYSICAL REVIEW RESEARCH. - 2643-1564. ; 2:3
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Tidskriftsartikel (refereegranskat)abstract
- We provide an argument to infer stationary entanglement between light and a mechanical oscillator based on continuous measurement of light only. We propose an experimentally realizable scheme involving an optomechanical cavity driven by a resonant, continuous-wave field operating in the non-sideband-resolved regime. This corresponds to the conventional configuration of an optomechanical position or force sensor. We show analytically that entanglement between the mechanical oscillator and the output field of the optomechanical cavity can be inferred from the measurement of squeezing in (generalized) Einstein-Podolski-Rosen quadratures of suitable temporal modes of the stationary light field. Squeezing can reach levels of up to 50% of noise reduction below shot noise in the limit of large quantum cooperativity. Remarkably, entanglement persists even in the opposite limit of small cooperativity. Viewing the optomechanical device as a position sensor, entanglement between mechanics and light is an instance of object-apparatus entanglement predicted by quantum measurement theory.
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