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@ARTICLE{Liew:179288,
      author       = {H. Liew$^*$ and S. Mein$^*$ and T. Tessonnier and A.
                      Abdollahi$^*$ and J. Debus$^*$ and I. Dokic$^*$ and A.
                      Mairani$^*$},
      title        = {{T}he {I}mpact of {S}ub-{M}illisecond {D}amage {F}ixation
                      {K}inetics on the {I}n {V}itro {S}paring {E}ffect at
                      {U}ltra-{H}igh {D}ose {R}ate in {UNIVERSE}.},
      journal      = {International journal of molecular sciences},
      volume       = {23},
      number       = {6},
      issn         = {1422-0067},
      address      = {Basel},
      publisher    = {Molecular Diversity Preservation International},
      reportid     = {DKFZ-2022-00570},
      pages        = {2954},
      year         = {2022},
      note         = {#EA:E050#LA:E210#},
      abstract     = {The 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.},
      keywords     = {FLASH (Other) / UNIVERSE (Other) / electrons (Other) /
                      ionizing radiation (Other) / modeling (Other) / temporal
                      pulse structure (Other) / ultra-high dose rate (Other)},
      cin          = {E050 / E210 / HD01},
      ddc          = {540},
      cid          = {I:(DE-He78)E050-20160331 / I:(DE-He78)E210-20160331 /
                      I:(DE-He78)HD01-20160331},
      pnm          = {315 - Bildgebung und Radioonkologie (POF4-315)},
      pid          = {G:(DE-HGF)POF4-315},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:35328377},
      pmc          = {pmc:PMC8954991},
      doi          = {10.3390/ijms23062954},
      url          = {https://inrepo02.dkfz.de/record/179288},
}