Finite-Difference and Pseudo-Sprectral Methods for the Numerical Simulations of In Vitro Human Tumor Cell Population Kinetics

Pseudo-spectral approximations are constructed for the model equations which describe the population kinetics of human tumor cells in vitro and their responses to radiotherapy or chemotherapy. These approximations are more efficient than finite-difference approximations. The spectral accuracy of the pseudo-spectral method allows us to resolve the model with a much smaller number of spatial grid-points than required for the finite-difference method to achieve comparable accuracy. This is demonstrated by numerical experiments which show a good agreement between predicted and experimental data

Modelling radiation-induced cell cycle delays

Ionizing radiation is known to delay the cell cycle progression. In particular after particle exposure significant delays have been observed and it has been shown that the extent of delay affects the expression of damage such as chromosome aberrations. Thus, to predict how cells respond to ionizing radiation and to derive reliable estimates of radiation risks, information about radiation-induced cell cycle perturbations is required. In the present study we describe and apply a method for retrieval of information about the time-course of all cell cycle phases from experimental data on the mitotic index only. We study the progression of mammalian cells through the cell cycle after exposure. The analysis reveals a prolonged block of damaged cells in the G2 phase. Furthermore, by performing an error analysis on simulated data valuable information for the design of experimental studies has been obtained. The analysis showed that the number of cells analyzed in an experimental sample should be at least 100 to obtain a relative error less than 20%.Comment: 19 pages, 11 figures, accepted for publication in Radiation and Environmental Biophysic

Global gene expression profiling of brown to white adipose tissue transformation in sheep reveals novel transcriptional components linked to adipose remodeling

BACKGROUND: Large mammals are capable of thermoregulation shortly after birth due to the presence of brown adipose tissue (BAT). The majority of BAT disappears after birth and is replaced by white adipose tissue (WAT). RESULTS: We analyzed the postnatal transformation of adipose in sheep with a time course study of the perirenal adipose depot. We observed changes in tissue morphology, gene expression and metabolism within the first two weeks of postnatal life consistent with the expected transition from BAT to WAT. The transformation was characterized by massively decreased mitochondrial abundance and down-regulation of gene expression related to mitochondrial function and oxidative phosphorylation. Global gene expression profiling demonstrated that the time points grouped into three phases: a brown adipose phase, a transition phase and a white adipose phase. Between the brown adipose and the transition phase 170 genes were differentially expressed, and 717 genes were differentially expressed between the transition and the white adipose phase. Thirty-eight genes were shared among the two sets of differentially expressed genes. We identified a number of regulated transcription factors, including NR1H3, MYC, KLF4, ESR1, RELA and BCL6, which were linked to the overall changes in gene expression during the adipose tissue remodeling. Finally, the perirenal adipose tissue expressed both brown and brite/beige adipocyte marker genes at birth, the expression of which changed substantially over time. CONCLUSIONS: Using global gene expression profiling of the postnatal BAT to WAT transformation in sheep, we provide novel insight into adipose tissue plasticity in a large mammal, including identification of novel transcriptional components linked to adipose tissue remodeling. Moreover, our data set provides a useful resource for further studies in adipose tissue plasticity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1405-8) contains supplementary material, which is available to authorized users

Role of IL-6 in Exercise Training- and Cold-Induced UCP1 Expression in Subcutaneous White Adipose Tissue

Expression of brown adipose tissue (BAT) associated proteins like uncoupling protein 1 (UCP1) in inguinal WAT (iWAT) has been suggested to alter iWAT metabolism. The aim of this study was to investigate the role of interleukin-6 (IL-6) in exercise training and cold exposure-induced iWAT UCP1 expression. The effect of daily intraperitoneal injections of IL-6 (3 ng/g) in C57BL/6 mice for 7 days on iWAT UCP1 expression was examined. In addition, the expression of UCP1 in iWAT was determined in response to 3 days of cold exposure (4°C) and 5 weeks of exercise training in wild type (WT) and whole body IL-6 knockout (KO) mice. Repeated injections of IL-6 in C57BL/6 mice increased UCP1 mRNA but not UCP1 protein content in iWAT. Cold exposure increased iWAT UCP1 mRNA content similarly in IL-6 KO and WT mice, while exercise training increased iWAT UCP1 mRNA in WT mice but not in IL-6 KO mice. Additionally, a cold exposure-induced increase in iWAT UCP1 protein content was blunted in IL-6 KO mice, while UCP1 protein content in iWAT was lower in both untrained and exercise trained IL-6 KO mice than in WT mice. In conclusion, repeated daily increases in plasma IL-6 can increase iWAT UCP1 mRNA content and IL-6 is required for an exercise training-induced increase in iWAT UCP1 mRNA content. In addition IL-6 is required for a full induction of UCP1 protein expression in response to cold exposure and influences the UCP1 protein content iWAT of both untrained and exercise trained animals

Structured models of cell migration incorporating molecular binding processes

The dynamic interplay between collective cell movement and the various molecules involved in the accompanying cell signalling mechanisms plays a crucial role in many biological processes including normal tissue development and pathological scenarios such as wound healing and cancer. Information about the various structures embedded within these processes allows a detailed exploration of the binding of molecular species to cell-surface receptors within the evolving cell population. In this paper we establish a general spatio-temporal-structural framework that enables the description of molecular binding to cell membranes coupled with the cell population dynamics. We first provide a general theoretical description for this approach and then illustrate it with two examples arising from cancer invasion

Ohmic energy confinement saturation and core toroidal rotation reversal in Alcator C-Mod plasmas

Ohmic energy confinement saturation is found to be closely related to core toroidal rotation reversals in Alcator C-Mod tokamak plasmas. Rotation reversals occur at a critical density, depending on the plasma current and toroidal magnetic field, which coincides with the density separating the linear Ohmic confinement regime from the saturated Ohmic confinement regime. The rotation is directed co-current at low density and abruptly changes direction to counter-current when the energy confinement saturates as the density is increased. Since there is a bifurcation in the direction of the rotation at this critical density, toroidal rotation reversal is a very sensitive indicator in the determination of the regime change. The reversal and confinement saturation results can be unified, since these processes occur in a particular range of the collisionality.United States. Dept. of Energy (Contract DE-FC02-99ER54512

Multi-dimensional parameter estimation of heavy-tailed moving averages

In this paper we present a parametric estimation method for certain multi-parameter heavy-tailed L\'evy-driven moving averages. The theory relies on recent multivariate central limit theorems obtained in [3] via Malliavin calculus on Poisson spaces. Our minimal contrast approach is related to the papers [14, 15], which propose to use the marginal empirical characteristic function to estimate the one-dimensional parameter of the kernel function and the stability index of the driving L\'evy motion. We extend their work to allow for a multi-parametric framework that in particular includes the important examples of the linear fractional stable motion, the stable Ornstein-Uhlenbeck process, certain CARMA(2, 1) models and Ornstein-Uhlenbeck processes with a periodic component among other models. We present both the consistency and the associated central limit theorem of the minimal contrast estimator. Furthermore, we demonstrate numerical analysis to uncover the finite sample performance of our method

Non-neoclassical up/down asymmetry of impurity emission on Alcator C-Mod

We demonstrate that existing theories are insufficient to explain up/down asymmetries of argon x-ray emission in Alcator C-Mod ohmic plasmas. Instead of the poloidal variation, ñ[subscript z]/〈n[subscript z]〉, being of order the inverse aspect ratio, ϵ, and scaling linearly with B[subscript t][superscript _ over n][subscript e]/I[2 over p], it is observed over 0.8 < r/a < 1.0 to be of order unity and exhibits a threshold behaviour between 3.5 <B[subscript t][superscript _ over n][subscript e]/I[subscript p] < 4.0 (T10[superscript 20] m[superscript −3] MA[superscript −1]). The transition from a poloidally symmetric to asymmetric impurity distribution is shown to occur at densities just below those that trigger a reversal of the core toroidal rotation direction, thought to be linked to the transition between the linear and saturated ohmic confinement regimes. A possible drive is discussed by which anomalous radial transport might sustain the impurity density asymmetry as the ratio of the perpendicular to parallel equilibration times, τ[subscript ⊥,z]/τ[subscript ∥,z], approaches unity. This explanation requires a strong up/down asymmetry in radial flux which, while not observable on C-Mod, has been measured in TEXT and Tore Supra ohmic plasmas.United States. Dept. of Energy (Contract DE-FC02-99ER54512)United States. Dept. of Energy (Fusion Research Postdoctoral Research Program

Neutrino cosmology and Planck

Relic neutrinos play an important role in the evolution of the Universe, modifying some of the cosmological observables. We summarize the main aspects of cosmological neutrinos and describe how the precision of present cosmological data can be used to learn about neutrino properties. In particular, we discuss how cosmology provides information on the absolute scale of neutrino masses, complementary to beta decay and neutrinoless double-beta decay experiments. We explain why the combination of Planck temperature data with measurements of the baryon acoustic oscillation angular scale provides a strong bound on the sum of neutrino masses, 0.23 eV at the 95% confidence level, while the lensing potential spectrum and the cluster mass function measured by Planck are compatible with larger values. We also review the constraints from current data on other neutrino properties. Finally, we describe the very good perspectives from future cosmological measurements, which are expected to be sensitive to neutrino masses close the minimum values guaranteed by flavour oscillations