Year of publication
- In silico analysis of cell cycle synchronisation effects in radiotherapy of tumour spheroids (2013)
- Abstract: Tumour cells show a varying susceptibility to radiation damage as a function of the current cell cycle phase. While this sensitivity is averaged out in an unperturbed tumour due to unsynchronised cell cycle progression, external stimuli such as radiation or drug doses can induce a resynchronisation of the cell cycle and consequently induce a collective development of radiosensitivity in tumours. Although this effect has been regularly described in experiments it is currently not exploited in clinical practice and thus a large potential for optimisation is missed. We present an agent-based model for three-dimensional tumour spheroid growth which has been combined with an irradiation damage and kinetics model. We predict the dynamic response of the overall tumour radiosensitivity to delivered radiation doses and describe corresponding time windows of increased or decreased radiation sensitivity. The degree of cell cycle resynchronisation in response to radiation delivery was identified as a main determinant of the transient periods of low and high radiosensitivity enhancement. A range of selected clinical fractionation schemes is examined and new triggered schedules are tested which aim to maximise the effect of the radiation-induced sensitivity enhancement. We find that the cell cycle resynchronisation can yield a strong increase in therapy effectiveness, if employed correctly. While the individual timing of sensitive periods will depend on the exact cell and radiation types, enhancement is a universal effect which is present in every tumour and accordingly should be the target of experimental investigation. Experimental observables which can be assessed non-invasively and with high spatio-temporal resolution have to be connected to the radiosensitivity enhancement in order to allow for a possible tumour-specific design of highly efficient treatment schedules based on induced cell cycle synchronisation. Author Summary: The sensitivity of a cell to a dose of radiation is largely affected by its current position within the cell cycle. While under normal circumstances progression through the cell cycle will be asynchronous in a tumour mass, external influences such as chemo- or radiotherapy can induce a synchronisation. Such a common progression of the inner clock of the cancer cells results in the critical dependence on the effectiveness of any drug or radiation dose on a suitable timing for its administration. We analyse the exact evolution of the radiosensitivity of a sample tumour spheroid in a computer model, which enables us to predict time windows of decreased or increased radiosensitivity. Fractionated radiotherapy schedules can be tailored in order to avoid periods of high resistance and exploit the induced radiosensitivity for an increase in therapy efficiency. We show that the cell cycle effects can drastically alter the outcome of fractionated irradiation schedules in a spheroid cell system. By using the correct observables and continuous monitoring, the cell cycle sensitivity effects have the potential to be integrated into treatment planing of the future and thus to be employed for a better outcome in clinical cancer therapies.
- Hadronization, chemical equilibrium and chemical freeze-out (2013)
- Recent results on baryon production in relativistic heavy ion collisions show that a revision of the chemical freeze-out conditions is necessary. Particularly, there is evidence that chemical freezeout does not occur at full chemical equilibrium. We present a method to reconstruct original hadronization conditions and show that the newly found points in the T − µB plane are in very good agreement with extrapolations of the lattice QCD critical line.
- Hadronic freeze-out in A+A collisions meets the lattice QCD parton-hadron transition line (2013)
- We analyze hadrochemical freeze-out in central Pb+Pb collisions at CERN SPS and LHC energies. Employing the UrQMD hybrid transport model we study the effects of the final hadron/resonance expansion phase on the hadron multiplicities established at hadronization. The bulk meson yields freeze out directly at hadronization whereas the baryon-antibaryon sector is subject to significant alterations, due to annihilation and regeneration processes. We quantify the latter changes by survival factors for each species which are applied to modify the statistical model predictions for the data. The modified SM analysis recovers the hadronization points, which coincide with the recent lattice QCD predictions of the parton-hadron transition line at finite baryochemical potential.
- Studies of dilepton production in coarse-grained transport dynamics (2013)
- As microscopic transport models usually have difficulties to deal with in-medium effects in heavy-ion collisions, we present an alternative approach that uses coarse-grained output from transport calculations with the UrQMD model to determine thermal dilepton emission rates. A four-dimensional space-time grid is set up to extract local baryon and energy densities, respectively temperature and baryon chemical potential. The lepton pair emission is then calculated for each cell of the grid using thermal equilibrium rates. In the current investigation we inlcude the medium-modified r spectral function by Eletsky et al., as well as contributions from the QGP and four-pion interactions for high collision energies. First dielectron invariant mass spectra for Au+Au collisions at 1.25 AGeV and for dimuons from In+In at 158 AGeV are shown. At 1.25 AGeV a clear enhancement of the total dilepton yield as compared to a pure transport result is observed. In the latter case, we compare our outcome with the NA60 dimuon excess data. Here a good agreement is achieved, but the yield in the low-mass tail is underestimated. In general the results show that the coarse-graining approach gives reasonable results and can cover a broad collision-energy range.
- Correlated D-meson decays competing against thermal QGP dilepton radiation (2013)
- The QGP that might be created in ultrarelativistic heavy-ion collisions is expected to radiate thermal dilepton radiation. However, this thermal dilepton radiation interferes with dileptons originating from hadron decays. In the invariant mass region between the f and J=y peak (1GeV <= M l+l <=. 3GeV) the most substantial background of hadron decays originates from correlated DD¯ -meson decays. We evaluate this background using a Langevin simulation for charm quarks. As background medium we utilize the well-tested UrQMD-hybrid model. The required drag and diffusion coefficients are taken from a resonance approach. The decoupling of the charm quarks from the hot medium is performed at a temperature of 130MeV and as hadronization mechanism a coalescence approach is chosen. This model for charm quark interactions with the medium has already been successfully applied to the study of the medium modification and the elliptic flow at FAIR, RHIC and LHC energies. In this proceeding we present our results for the dilepton radiation from correlated D¯D decays at RHIC energy in comparison to PHENIX measurements in the invariant mass range between 1 and 3 GeV using different interaction scenarios. These results can be utilized to estimate the thermal QGP radiation.
- Dynamic enhancement of fluctuation signals at the QCD phase transition (2013)
- We study the impact of nonequilibrium effects on the relevant signals within a chiral fluid dynamics model including explicit propagation of the Polyakov loop. An expanding heat bath of quarks is coupled to the Langevin dynamics of the order parameter fields. The model is able to describe relaxational processes, including critical slowing down and the enhancement of soft modes near the critical point. At the first-order phase transition we observe domain formation and phase coexistence in the sigma and Polyakov loop field leading to a significant amount of clumping in the energy density. This effect gets even more pronounced if we go to systems at finite baryon density. Here the formation of high-density clusters could provide an important observable signal for upcoming experiments at FAIR and NICA.We conclude that improving our understanding of dynamical symmetry breaking is important to give realistic estimates for experimental observables connected to the QCD phase transition.
- Nanolesions induced by heavy ions in human tissues: experimental and theoretical studies (2012)
- The biological effects of energetic heavy ions are attracting increasing interest for their applications in cancer therapy and protection against space radiation. The cascade of events leading to cell death or late effects starts from stochastic energy deposition on the nanometer scale and the corresponding lesions in biological molecules, primarily DNA. We have developed experimental techniques to visualize DNA nanolesions induced by heavy ions. Nanolesions appear in cells as “streaks” which can be visualized by using different DNA repair markers. We have studied the kinetics of repair of these “streaks” also with respect to the chromatin conformation. Initial steps in the modeling of the energy deposition patterns at the micrometer and nanometer scale were made with MCHIT and TRAX models, respectively.
- Hybrid approaches to heavy ion collisions and future perspectives (2011)
- We present the current status of hybrid approaches to describe heavy ion collisions and their future challenges and perspectives. First we present a hybrid model combining a Boltzmann transport model of hadronic degrees of freedom in the initial and final state with an optional hydrodynamic evolution during the dense and hot phase. Second, we present a recent extension of the hydrodynamical model to include fluctuations near the phase transition by coupling a chiral field to the hydrodynamic evolution.
- Multi-particle interactions within the UrQMD approach (2011)
- A mechanism for locally density-dependent dynamic parton rearrangement and fusion has been implemented into the Ultrarelativistic Quantum Molecular Dynamics (UrQMD) approach. The same mechanism has been previously built in the Quark Gluon String Model (QGSM). This rearrangement and fusion approach based on parton coalescence ideas enables the description of multi-particle interactions, namely 3 -> 3 and 3 -> 2, between (pre)hadronic states in addition to standard binary interactions. The UrQMD model (v2.3) extended by these additional processes allows to investigate implications of multi-particle interactions on the reaction dynamics of ultrarelativistic heavy ion collisions. The mechanism, its implementation and first results of this investigation are presented and discussed.
- HBT radii from the UrQMD transport approach at different energies (2011)
- We present results on Hanbury Brown-Twiss (HBT) radii extracted from the Ultra-relativistic Molecular Dynamics (UrQMD) approach to relativistic heavy ion collisions. The present investigation provides a comparison of results from pure hadronic transport calculations to a Boltzmann + Hydrodynamic hybrid approach with an intermediate hydrodynamic phase. For the hydrodynamic phase different Equations of State (EoS) have been employed, i.e. bag model, hadron resonance gas and a chiral EoS. The influence of various freeze-out scenarios has been investigated and shown to be negligible if hadronic rescatterings after the hydrodynamic evolution are included. Furthermore, first results of the source tilt from azimuthal sensitive HBT and the direct extraction from the transport model are presented and exhibit a very good agreement with E895 data at AGS.