Escape of cosmic rays from perpendicular shocks in the circumstellar magnetic field

We investigate the escape process of cosmic rays (CRs) from perpendicular shock regions of a spherical shock propagating to a circumstellar medium with the Parker-spiral magnetic field. The diffusive shock acceleration in perpendicular shocks of supernova remnants (SNRs) is expected to accelerate CRs up to PeV without upstream magnetic field amplification. Red supergiants (RSGs) and Wolf-Rayet (WR) stars are considered as progenitors in this work. We perform test particle simulations to investigate the escape process and escape-limited maximum energy without magnetic field amplification in the upstream region, where the magnetic field strength and rotation period expected from observations of RSGs and WR stars are used. We show that particles escape to the far upstream region while moving along the equator or poles and the maximum energy is about $10-100~{\rm TeV}$ when SNRs propagate to free wind regions of RSGs and WR stars. In most cases, the escape-limited maximum energy is given by the potential difference between the equator and pole. If progenitors are oblique rotators and SNRs are in the early phase just after the supernova explosion, the escape-limited maximum energy is limited by the half wavelength of the wavy current sheet. In addition, for RSGs, we show that the luminosity of CRs accelerated in the wind region is sufficient to supply the observed CR flux above $10~{\rm TeV}$ if a strong magnetic field strength is sustained in most RSGs. In terms of the CR luminosity, SNRs propagating to the free wind of WR stars can contribute to PeV CRs. As long as no magnetic field amplification works around SNR shocks, the maximum energy is decided by the magnetic field strength in the wind region, which depends on the rotation period, stellar wind, and surface magnetic field of RSGs and WR stars. Therefore, we need to observe these quantities to understand the origin of CRs.Comment: 20 pages, 19 figures, accepted for publication in PR

Thermodynamic Uncertainty Relations for Steady-State Thermodynamics

A system can be driven out of equilibrium by both time-dependent and nonconservative forces, which gives rise to a decomposition of the dissipation into two non-negative components, called the excess and housekeeping entropy productions. We derive thermodynamic uncertainty relations for the excess and housekeeping entropy. These can be used as tools to estimate the individual components, which are in general difficult to measure directly. We introduce a decomposition of an arbitrary current into excess and housekeeping parts, which provide lower bounds on the respective entropy production. Furthermore, we also provide a geometric interpretation of the decomposition, and show that the uncertainties of the two components are not independent, but rather have to obey a joint uncertainty relation, which also yields a tighter bound on the total entropy production. We apply our results to two examples that illustrate the physical interpretation of the components of the current and how to estimate the entropy production.Comment: 14 pages, 10 figure

Radiosensitization of gliomas by intracellular generation of 5-fluorouracil potentiates prodrug activator gene therapy with a retroviral replicating vector.

A tumor-selective non-lytic retroviral replicating vector (RRV), Toca 511, and an extended-release formulation of 5-fluorocytosine (5-FC), Toca FC, are currently being evaluated in clinical trials in patients with recurrent high-grade glioma (NCT01156584, NCT01470794 and NCT01985256). Tumor-selective propagation of this RRV enables highly efficient transduction of glioma cells with cytosine deaminase (CD), which serves as a prodrug activator for conversion of the anti-fungal prodrug 5-FC to the anti-cancer drug 5-fluorouracil (5-FU) directly within the infected cells. We investigated whether, in addition to its direct cytotoxic effects, 5-FU generated intracellularly by RRV-mediated CD/5-FC prodrug activator gene therapy could also act as a radiosensitizing agent. Efficient transduction by RRV and expression of CD were confirmed in the highly aggressive, radioresistant human glioblastoma cell line U87EGFRvIII and its parental cell line U87MG (U87). RRV-transduced cells showed significant radiosensitization even after transient exposure to 5-FC. This was confirmed both in vitro by a clonogenic colony survival assay and in vivo by bioluminescence imaging analysis. These results provide a convincing rationale for development of tumor-targeted radiosensitization strategies utilizing the tumor-selective replicative capability of RRV, and incorporation of radiation therapy into future clinical trials evaluating Toca 511 and Toca FC in brain tumor patients

Eщё paз o H. C. Xpyщёвe

長砂賓教授古稀記念特

Mixing time and simulated annealing for the stochastic cellular automata

Finding a ground state of a given Hamiltonian on a graph $G=(V,E)$ is an important but hard problem. One of the potential approaches is to use a Markov chain Monte Carlo to sample the Gibbs distribution whose highest peaks correspond to the ground states. In this paper, we investigate a particular kind of stochastic cellular automata, in which all spins are updated independently and simultaneously. We prove that (i) if the temperature is fixed sufficiently high, then the mixing time is at most of order $\log|V|$, and that (ii) if the temperature drops in time $n$ as $1/\log n$, then the limiting measure is uniformly distributed over the ground states.Comment: 16 pages, 8 figure