Renormalization of radiobiological response functions by energy loss fluctuations and complexities in chromosome aberration induction: deactivation theory for proton therapy from cells to tumor control

We employ a multi-scale mechanistic approach to investigate radiation induced cell toxicities and deactivation mechanisms as a function of linear energy transfer in hadron therapy. Our theoretical model consists of a system of Markov chains in microscopic and macroscopic spatio-temporal landscapes, i.e., stochastic birth-death processes of cells in millimeter-scale colonies that incorporates a coarse-grained driving force to account for microscopic radiation induced damage. The coupling, hence the driving force in this process, stems from a nano-meter scale radiation induced DNA damage that incorporates the enzymatic end-joining repair and mis-repair mechanisms. We use this model for global fitting of the high-throughput and high accuracy clonogenic cell-survival data acquired under exposure of the therapeutic scanned proton beams, the experimental design that considers $\gamma$-H2AX as the biological endpoint and exhibits maximum observed achievable dose and LET, beyond which the majority of the cells undergo collective biological deactivation processes. An estimate to optimal dose and LET calculated from tumor control probability by extension to $~ 10^6$ cells per $mm$-size voxels is presented. We attribute the increase in degree of complexity in chromosome aberration to variabilities in the observed biological responses as the beam linear energy transfer (LET) increases, and verify consistency of the predicted cell death probability with the in-vitro cell survival assay of approximately 100 non-small cell lung cancer (NSCLC) cells

Robust H8 design for resonant control in a CVCF inverter application over load uncertainties

CVCF (constant voltage, constant frequency) inverters are electronic devices used to supply AC loads from DC storage elements such as batteries or photovoltaic cells. These devices are used to feed different kinds of loads; this uncertainty requires that the controller fulfills robust stability conditions while keeping required performance. To address this, a robust H8 design is proposed based on resonant control to track a pure sinusoidal voltage signal and to reject the most common harmonic signals in a wide range of loads. The design is based on the definition of performance bounds in error signal and weighting functions for covering most uncertainty ranges in loads. Experimentally, the H8 controller achieves high-quality output voltage signal with a total harmonic distortion less than 2%Peer ReviewedPostprint (published version

Thermostatistics of extensive and non-extensive systems using generalized entropies

We describe in detail two numerical simulation methods valid to study systems whose thermostatistics is described by generalized entropies, such as Tsallis. The methods are useful for applications to non-trivial interacting systems with a large number of degrees of freedom, and both short-range and long-range interactions. The first method is quite general and it is based on the numerical evaluation of the density of states with a given energy. The second method is more specific for Tsallis thermostatistics and it is based on a standard Monte Carlo Metropolis algorithm along with a numerical integration procedure. We show here that both methods are robust and efficient. We present results of the application of the methods to the one-dimensional Ising model both in a short-range case and in a long-range (non-extensive) case. We show that the thermodynamic potentials for different values of the system size N and different values of the non-extensivity parameter q can be described by scaling relations which are an extension of the ones holding for the Boltzmann-Gibbs statistics (q=1). Finally, we discuss the differences in using standard or non-standard mean value definitions in the Tsallis thermostatistics formalism and present a microcanonical ensemble calculation approach of the averages.Comment: Submitted to Physica A. LaTeX format, 38 pages, 17 EPS figures. IMEDEA-UIB, 07071 Palma de Mallorca, Spain, http://www.imedea.uib.e

Lineal Trails of D2-D2bar Superstrings

We study the superstrings suspended between a D2- and an anti-D2-brane. We quantize the string in the presence of some general configuration of gauge fields over the (anti-)D-brane world volumes. The interstring can move only in a specific direction that is normal to the difference of the electric fields of each (anti-)D-branes. Especially when the electric fields are the same, the interstring cannot move. We obtain the condition for the tachyons to disappear from the spectrum.Comment: 15 pages with 4 figures, referenced added, Sec. 5 on the spectrum made cleare

Analytical and numerical study of some variants of Koiter's linear model of thin shells

Koiter's linear model for thin shells is obtained from the classic equations of the three-dimensional linear elasticity with the Kirchhoff-Love hypothesis; the variety of formulations of this model is based on the precision of the analysis carried out. In this work we detail these simplifications, and analyse the origin and the error of some variations of the model. We also approximate some of these versions by a nonconforming finite element method and compare the numerical results over some classical bench-marks