In silico analysis of cell cycle synchronisation effects in radiotherapy of tumour spheroids
- 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.
From p+p to Pb+Pb collisions: wounded nucleon versus statistical models
- System size dependence of hadron production properties is discussed within the Wounded Nucleon Model and the Statistical Model in the grand canonical, canonical and micro-canonical formulations. Similarities and differences between predictions of the models related to the treatment of conservation laws are exposed. A need for models which would combine a hydrodynamicallike expansion with conservation laws obeyed in individual collisions is stressed.
Generating functionals for autonomous latching dynamics in attractor relict networks
- Coupling local, slowly adapting variables to an attractor network allows to destabilize all attractors, turning them into attractor ruins. The resulting attractor relict network may show ongoing autonomous latching dynamics. We propose to use two generating functionals for the construction of attractor relict networks, a Hopfield energy functional generating a neural attractor network and a functional based on information-theoretical principles, encoding the information content of the neural firing statistics, which induces latching transition from one transiently stable attractor ruin to the next. We investigate the influence of stress, in terms of conflicting optimization targets, on the resulting dynamics. Objective function stress is absent when the target level for the mean of neural activities is identical for the two generating functionals and the resulting latching dynamics is then found to be regular. Objective function stress is present when the respective target activity levels differ, inducing intermittent bursting latching dynamics.
Neuropsychological constraints to human data production on a global scale
- Which are the factors underlying human information production on a global level? In order to gain an insight into this question we study a corpus of 252–633 mil. publicly available data files on the Internet corresponding to an overall storage volume of 284–675 Terabytes. Analyzing the file size distribution for several distinct data types we find indications that the neuropsychological capacity of the human brain to process and record information may constitute the dominant limiting factor for the overall growth of globally stored information, with real-world economic constraints having only a negligible influence. This supposition draws support from the observation that the files size distributions follow a power law for data without a time component, like images, and a log-normal distribution for multimedia files, for which time is a defining qualia.
Author summary: The generation of new information is limited by two key factors, by the incurring economic costs and by the capacity of the human brain to process and store data and information; the controlling agent needs to retain an overall understanding even when data is generated by semiautomatic processes. These processes are reflected in the statistical properties of the data files publicly available on the Internet. Collecting a corpus of 252–633 mil. files we find that the statistics of the file size distribution are consistent with the supposition that data production on a global level is shaped and limited by the neuropsychological information processing capacity of the brain, with economic and hardware constraints having a negligible influence.
Are v1 simple cells optimized for visual occlusions? : A comparative study
- Abstract: Simple cells in primary visual cortex were famously found to respond to low-level image components such as edges. Sparse coding and independent component analysis (ICA) emerged as the standard computational models for simple cell coding because they linked their receptive fields to the statistics of visual stimuli. However, a salient feature of image statistics, occlusions of image components, is not considered by these models. Here we ask if occlusions have an effect on the predicted shapes of simple cell receptive fields. We use a comparative approach to answer this question and investigate two models for simple cells: a standard linear model and an occlusive model. For both models we simultaneously estimate optimal receptive fields, sparsity and stimulus noise. The two models are identical except for their component superposition assumption. We find the image encoding and receptive fields predicted by the models to differ significantly. While both models predict many Gabor-like fields, the occlusive model predicts a much sparser encoding and high percentages of ‘globular’ receptive fields. This relatively new center-surround type of simple cell response is observed since reverse correlation is used in experimental studies. While high percentages of ‘globular’ fields can be obtained using specific choices of sparsity and overcompleteness in linear sparse coding, no or only low proportions are reported in the vast majority of studies on linear models (including all ICA models). Likewise, for the here investigated linear model and optimal sparsity, only low proportions of ‘globular’ fields are observed. In comparison, the occlusive model robustly infers high proportions and can match the experimentally observed high proportions of ‘globular’ fields well. Our computational study, therefore, suggests that ‘globular’ fields may be evidence for an optimal encoding of visual occlusions in primary visual cortex.
Author Summary: The statistics of our visual world is dominated by occlusions. Almost every image processed by our brain consists of mutually occluding objects, animals and plants. Our visual cortex is optimized through evolution and throughout our lifespan for such stimuli. Yet, the standard computational models of primary visual processing do not consider occlusions. In this study, we ask what effects visual occlusions may have on predicted response properties of simple cells which are the first cortical processing units for images. Our results suggest that recently observed differences between experiments and predictions of the standard simple cell models can be attributed to occlusions. The most significant consequence of occlusions is the prediction of many cells sensitive to center-surround stimuli. Experimentally, large quantities of such cells are observed since new techniques (reverse correlation) are used. Without occlusions, they are only obtained for specific settings and none of the seminal studies (sparse coding, ICA) predicted such fields. In contrast, the new type of response naturally emerges as soon as occlusions are considered. In comparison with recent in vivo experiments we find that occlusive models are consistent with the high percentages of center-surround simple cells observed in macaque monkeys, ferrets and mice.
Nonthermal phase transitions in semiconductors induced by a femtosecond extreme ultraviolet laser pulse
Harald O. Jeschke
- Part of Focus on High Energy Density Physics. In this paper, we present a novel theoretical approach, which allows the study of nonequilibrium dynamics of both electrons and atoms/ions within free-electron laser excited semiconductors at femtosecond time scales. The approach consists of the Monte-Carlo method treating photoabsorption, high-energy-electron and core-hole kinetics and relaxation processes. Low-energy electrons localized within the valence and conduction bands of the target are treated with a temperature equation, including source terms, defined by the exchange of energy and particles with high-energy electrons and atoms. We follow the atomic motion with the molecular dynamics method on the changing potential energy surface. The changes of the potential energy surface and of the electron band structure are calculated at each time step with the help of the tight-binding method. Such a combination of methods enables investigation of nonequilibrium structural changes within materials under extreme ultraviolet (XUV) femtosecond irradiation. Our analysis performed for diamond irradiated with an XUV femtosecond laser pulse predicts for the first time in this wavelength regime the nonthermal phase transition from diamond to graphite. Similar to the case of visible light irradiation, this transition takes place within a few tens of femtoseconds and is caused by changes of the interatomic potential induced by ultrafast electronic excitations. It thus occurs well before the heating stimulated by electron–phonon coupling starts to play a role. This allows us to conclude that this transition is nonthermal and represents a general mechanism of the response of solids to ultrafast electron excitations.
CAST constraints on the axion-electron coupling
José Manuel Carmona
Juan I. Collar
Luigi Di Lella
J. A. García
Michael D. Hasinoff
Fritz Herbert Heinsius
Dieter H.H. Hoffmann
Igor Garcia Irastorza
David W. Miller
Mike J. Pivovaroff
Karl van Bibber
Joaquin D. Vieira
José A. Villar
Julia K. Vogel
- In non-hadronic axion models, which have a tree-level axion-electron interaction, the Sun produces a strong axion flux by bremsstrahlung, Compton scattering, and axiorecombination, the “BCA processes.” Based on a new calculation of this flux, including for the first time axio-recombination, we derive limits on the axion-electron Yukawa coupling gae and axion-photon interaction strength ga using the CAST phase-I data (vacuum phase). For ma <~ 10 meV/c2 we find ga gae < 8.1 × 10−23 GeV−1 at 95% CL. We stress that a next-generation axion helioscope such as the proposed IAXO could push this sensitivity into a range beyond stellar energy-loss limits and test the hypothesis that white-dwarf cooling is dominated by axion emission.
Electron supersurface scattering on polycrystalline Au
Wolfgang S. M. Werner
- Supersurface electron scattering, i.e., electron energy losses and associated deflections in vacuum above the surface of a medium, is shown to contribute significantly to electron spectra. We have obtained experimental verification (in absolute units) of theoretical predictions that the angular distribution of the supersurface backscattering probability exhibits strong oscillations which are anticorrelated with the generalized Ramsauer-Townsend minima in the backscattering probability. We have investigated 500-eV electron backscattering from an Au surface for an incidence angle of 70° and scattering angles between 37° and 165°. After removing the contribution of supersurface scattering from the experimental data, the resulting angular and energy distribution agrees with the Landau-Goudsmit-Saunderson (LGS) theory, which was proposed about 60 years ago, while the raw data are anticorrelated with LGS theory. This result implies that supersurface scattering is an essential phenomenon for quantitative understanding of electron spectra.
Spin modulation instabilities and phase separation dynamics in trapped two-component Bose condensates
Nicolaas Jan van Druten
- In the study of trapped two-component Bose gases, a widely used dynamical protocol is to start from the ground state of a one-component condensate and then switch half the atoms into another hyperfine state. The slightly different intra-component and inter-component interactions can then lead to highly non-trivial dynamics, especially in the density mismatch between the two components, commonly referred to as 'spin' density. We study and classify the possible subsequent dynamics, over a wide variety of parameters spanned by the trap strength and by the inter- to intra-component interaction ratio. A stability analysis suited to the trapped situation provides us with a framework to explain the various types of dynamics in different regimes.
Visual working memory contents bias ambiguous structure from motion perception
Karl R. Gegenfurtner
- The way we perceive the visual world depends crucially on the state of the observer. In the present study we show that what we are holding in working memory (WM) can bias the way we perceive ambiguous structure from motion stimuli. Holding in memory the percept of an unambiguously rotating sphere influenced the perceived direction of motion of an ambiguously rotating sphere presented shortly thereafter. In particular, we found a systematic difference between congruent dominance periods where the perceived direction of the ambiguous stimulus corresponded to the direction of the unambiguous one and incongruent dominance periods. Congruent dominance periods were more frequent when participants memorized the speed of the unambiguous sphere for delayed discrimination than when they performed an immediate judgment on a change in its speed. The analysis of dominance time-course showed that a sustained tendency to perceive the same direction of motion as the prior stimulus emerged only in the WM condition, whereas in the attention condition perceptual dominance dropped to chance levels at the end of the trial. The results are explained in terms of a direct involvement of early visual areas in the active representation of visual motion in WM.