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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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- Carter, J. A., et al.
(författare)
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Ground-based and additional science support for SMILE
- 2024
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Ingår i: Earth and Planetary Physics. - : Science Press. - 2096-3955. ; 8:1, s. 275-298
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Tidskriftsartikel (refereegranskat)abstract
- The joint European Space Agency and Chinese Academy of Sciences Solar wind Magnetosphere Ionosphere Link Explorer (SMILE) mission will explore global dynamics of the magnetosphere under varying solar wind and interplanetary magnetic field conditions, and simultaneously monitor the auroral response of the Northern Hemisphere ionosphere. Combining these large-scale responses with medium and fine-scale measurements at a variety of cadences by additional ground-based and space-based instruments will enable a much greater scientific impact beyond the original goals of the SMILE mission. Here, we describe current community efforts to prepare for SMILE, and the benefits and context various experiments that have explicitly expressed support for SMILE can offer. A dedicated group of international scientists representing many different experiment types and geographical locations, the Ground-based and Additional Science Working Group, is facilitating these efforts. Preparations include constructing an online SMILE Data Fusion Facility, the discussion of particular or special modes for experiments such as coherent and incoherent scatter radar, and the consideration of particular observing strategies and spacecraft conjunctions. We anticipate growing interest and community engagement with the SMILE mission, and we welcome novel ideas and insights from the solar-terrestrial community.
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- Wang, ZJ., et al.
(författare)
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Metabolic flux analysis of the central carbon metabolism of the industrial vitamin B-12 producing strain Pseudomonas denitrificans using C-13-labeled glucose
- 2012
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Ingår i: Journal of the Taiwan Institute of Chemical Engineers. - : Elsevier BV. - 1876-1070. ; 43:2, s. 181-187
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Tidskriftsartikel (refereegranskat)abstract
- The network topology and metabolic fluxes of central carbon metabolism in the industrial vitamin B-12 producing strain Pseudomonas denitrificans were characterized under oxygen limiting levels. Cultivations were carried out with 100% [1-C-13] or 20% [U-C-13] glucose as substrates under different oxygen supply conditions. The labeling patterns of the proteinogenic amino acids of exponentially growing cells were used to accurately estimate the fluxes in the central carbon metabolism of P. denitrificans. Metabolic flux analysis showed that glucose was mostly catabolized by the Entner-Doudoroff and pentose phosphate pathways. Up to 33% of glucose was consumed via the PP pathway under high specific oxygen uptake rate (SOUR) conditions. This amount was 77.9% higher than that under low oxygen uptake conditions. Quantitative evidence was also found for reversible serine hydroxymethyl transferase and threonine aldolase activities. Metabolic flux and cofactor analyses further showed that higher SOUR accelerated the supply of precursors and methyl groups. SOUR also provided more NADPH for higher vitamin B12 production under the same glucose consumption.
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- Whitlow, Harry J, et al.
(författare)
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Fundamental effects and non-linear Si detector response
- 2002
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Ingår i: Nuclear Instruments & Methods in Physics Research. Section B: Beam Interactions with Materials and Atoms. - 0168-583X. ; 190:1-4, s. 375-378
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Tidskriftsartikel (refereegranskat)abstract
- Non-linearity in the energy response of a Si p-i-n charged particle detector has been studied for incident particles with Z(1) between 3 and 26, and energies between 0.1 and 0.7 MeV per nucleon. Although the data closely followed a straight line relations, fitting of the data to a third order polynomial revealed that the response exhibited a persistent curvature that acted to reduce the energy interval spanned by a channel as the energy increased. The curvature increased as Z(1) increased from 4 to 8 and then systematically decreased. The curvature is larger and has the opposite energy dependence to the stopping in a dead entrance window and the energy deposited in non-ionising processes within the active layer. The plasma recombination dependence on the average stopping along the plasma column may account for the reduction in curvature as Z(1) increases from 9 to 25 but cannot explain the net effect. The low-energy increase in energy channel span, which has also been reported by others, might be associated with electron excitation in resonant and direct classical quasi-elastic collisions for low-energy ions, or less likely, electronic non-linearity's associated with Z(1) and energy dependent time structure in the current pulse from the detector. Simple interpolation of the window-loss corrected polynomial coefficients is the best approach if the calibration for Z(1) cannot be established directly.
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- Whitlow, Harry J, et al.
(författare)
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Measurement and uncertainties of energy loss in silicon over a wide Z(1) range using time of flight detector telescopes
- 2002
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Ingår i: Nuclear Instruments & Methods in Physics Research. Section B: Beam Interactions with Materials and Atoms. - 0168-583X. ; 195:1-2, s. 133-146
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Tidskriftsartikel (refereegranskat)abstract
- The energy loss of projectiles with Z(1) in the range 3-26 has been experimentally measured in the 0.1-0.7 MeV per nucleon energy range in the same Si stopping foil of 105.5 mug cm(-2) thickness using a time of flight-energy (ToF-E) elastic recoil detection analysis (ERDA) setup. A detailed study of the experimental uncertainties for ToF-E and ToF-ToF-E configuration has been made. For ERDA configurations where the energy calibration is taken against the edge positions small uncertainties in the angle at which recoils are detected can introduce significant, absolute uncertainty. The relative uncertainty contribution is dominated by the energy calibration of the Si E detector for the ToF-E configuration and the position of the second ToF detector in ToF-ToF-E measurements. The much smaller calibration uncertainty for ToF-ToF-E configuration implies this technique is superior to ToF-E measurements with Si E detectors. At low energies the effect of charge changing in the time detector foils can become important. It was found that empirical stopping numbers which include the effect of effective-charge were more closely clustered about a trend line when plotted against the Bohr parameter than the corresponding Bethe parameter. Study of the deviations from the trend line showed evidence of a shell dependant effect that exceeded the anticipated maximum relative uncertainties.
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| 10. |
- Zhang, YW, et al.
(författare)
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Electronic stopping powers for heavy ions in silicon
- 2004
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Ingår i: Nuclear Instruments & Methods in Physics Research. Section B: Beam Interactions with Materials and Atoms. - : Elsevier BV. - 0168-583X. ; 215:1-2, s. 48-56
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Tidskriftsartikel (refereegranskat)abstract
- The stopping powers in silicon of heavy ions, with atomic numbers ranging from 4 to 29, have been determined using a time-of-flight elastic recoil detection analysis (TOF ERDA) set-up. In transmission geometry, the energy loss of heavy elastic recoils in the self-supporting silicon foil of known thickness is measured over a continuous range of recoil energies using time-of-flight (TOF) spectrometry. By essentially calibrating the Si detector for each channel over the measured energy region using the TOF spectrometer, an uncertainty of less than 4% is achieved. The stopping powers are parameterized using a sixth order polynomial and compared with the limited experimental data in the literature. In the energy regimes Where experimental data exist, the present data exhibit good agreement with most data. Stopping powers predicted by SRIM (the stopping and range of ions in matter) are in reasonable agreement with much of the experimental data, and SRIM-2003 predictions are in somewhat better agreement than SRIM-2000. There are, however, still some discrepancies between SRIM predictions and the experimental data. (C) 2003 Elsevier B.V. All rights reserved.
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