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000179288 1001_ $$0P:(DE-He78)dc4247d1e899d0fd333732064f422a0f$$aLiew, Hans$$b0$$eFirst author$$udkfz
000179288 245__ $$aThe Impact of Sub-Millisecond Damage Fixation Kinetics on the In Vitro Sparing Effect at Ultra-High Dose Rate in UNIVERSE.
000179288 260__ $$aBasel$$bMolecular Diversity Preservation International$$c2022
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000179288 520__ $$aThe impact of the exact temporal pulse structure on the potential cell and tissue sparing of ultra-high dose-rate irradiation applied in FLASH studies has gained increasing attention. A previous version of our biophysical mechanistic model (UNIVERSE: UNIfied and VERSatile bio response Engine), based on the oxygen depletion hypothesis, has been extended in this work by considering oxygen-dependent damage fixation dynamics on the sub-milliseconds scale and introducing an explicit implementation of the temporal pulse structure. The model successfully reproduces in vitro experimental data on the fast kinetics of the oxygen effect in irradiated mammalian cells. The implemented changes result in a reduction in the assumed amount of oxygen depletion. Furthermore, its increase towards conventional dose-rates is parameterized based on experimental data from the literature. A recalculation of previous benchmarks shows that the model retains its predictive power, while the assumed amount of depleted oxygen approaches measured values. The updated UNIVERSE could be used to investigate the impact of different combinations of pulse structure parameters (e.g., dose per pulse, pulse frequency, number of pulses, etc.), thereby aiding the optimization of potential clinical application and the development of suitable accelerators.
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000179288 650_7 $$2Other$$aFLASH
000179288 650_7 $$2Other$$aUNIVERSE
000179288 650_7 $$2Other$$aelectrons
000179288 650_7 $$2Other$$aionizing radiation
000179288 650_7 $$2Other$$amodeling
000179288 650_7 $$2Other$$atemporal pulse structure
000179288 650_7 $$2Other$$aultra-high dose rate
000179288 7001_ $$0P:(DE-HGF)0$$aMein, Stewart$$b1
000179288 7001_ $$0P:(DE-He78)b907c008f5a279f1f3539ca77ec858dc$$aTessonnier, Thomas$$b2$$udkfz
000179288 7001_ $$0P:(DE-He78)360c5bc2b71a849e35aca747c041dda7$$aAbdollahi, Amir$$b3$$udkfz
000179288 7001_ $$0P:(DE-He78)8714da4e45acfa36ce87c291443a9218$$aDebus, Jürgen$$b4$$udkfz
000179288 7001_ $$0P:(DE-He78)e24b607ded082a3089a1f6bf326a7a8e$$aDokic, Ivana$$b5$$udkfz
000179288 7001_ $$0P:(DE-He78)8d6c2aceda79e88defe1e8c0fcc39d59$$aMairani, Andrea$$b6$$eLast author$$udkfz
000179288 773__ $$0PERI:(DE-600)2019364-6$$a10.3390/ijms23062954$$gVol. 23, no. 6, p. 2954 -$$n6$$p2954$$tInternational journal of molecular sciences$$v23$$x1422-0067$$y2022
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