Dynamic remodeling of the intrahepatic biliary epithelial tissue plays key roles in liver regeneration, yet the cellular basis for this process remains unclear. We took an unbiased approach based on in vivo clonal labeling and tracking of biliary epithelial cells in the three-dimensional landscape, in combination with mathematical simulation, to understand their mode of proliferation in a mouse liver injury model where the nascent biliary structure formed in a tissue-intrinsic manner. An apparent heterogeneity among biliary epithelial cells was observed: whereas most of the responders that entered the cell cycle upon injury exhibited a limited and tapering growth potential, a select population continued to proliferate, making a major contribution in sustaining the biliary expansion. Our study has highlighted a unique mode of epithelial tissue dynamics, which depends not on a hierarchical system driven by fixated stem cells, but rather, on a stochastically maintained progenitor population with persistent proliferative activity.DOI: http://dx.doi.org/10.7554/eLife.15034.001

We report the demonstrated irradiation effect of laser-accelerated protons on human cancer cells. In vitro (living) A549 cells are irradiated with quasimonoenergetic proton bunches of 0.8–2.4 MeV with a single bunch duration of 15 ns. Irradiation with the proton dose of 20 Gy results in a distinct formation of γ-H2AX foci as an indicator of DNA double-strand breaks generated in the cancer cells. This is a pioneering result that points to future investigations of the radiobiological effects of laser-driven ion beams. Unique high-current and short-bunch features make laser-driven proton bunches an excitation source for time-resolved determination of radical yields.

Human cancer cells are irradiated by laser-driven quasimonoenergetic protons. Laser pulse intensities at the 5×1019 W/cm2 level provide the source and acceleration field for protons that are subsequently transported by four energy-selective dipole magnets. The transport line delivers 2.25 MeV protons with an energy spread of 0.66 MeV and a bunch duration of 20 ns. The survival fraction of in vitro cells from a human salivary gland tumor is measured with a colony formation assay following proton irradiation at dose levels of up to 8 Gy, for which the single bunch dose rate is 1×107 Gy/s and the effective dose rate is 0.2 Gy/s for 1 Hz repetition of irradiation. Relative biological effectiveness at the 10% survival fraction is measured to be 1.20±0.11 using protons with a linear energy transfer of 17.1 keV/μm.

Optical parametric chirped-pulse amplification (OPCPA) operation with low gain by seeding with high-energy, clean pulses is shown to significantly improve the contrast to better than 10(-10) to 10(-11) in a high-intensity Ti:sapphire laser system that is based on chirped-pulse amplification. In addition to the high-contrast broadband, high-energy output from the final amplifier is achieved with a flat-topped spatial profile of filling factor near 77%. This is the result of pump beam spatial profile homogenization with diffractive optical elements. Final pulse energies exceed 30 J, indicating capability for reaching peak powers in excess of 500 TW.

Laser light reflection by a relativistically moving electron density modulation (flying mirror) in a wake wave generated in a plasma by a high intensity laser pulse is investigated experimentally. A counterpropagating laser pulse is reflected and upshifted in frequency with a multiplication factor of 37-66, corresponding to the extreme ultraviolet wavelength. The demonstrated flying mirror reflectivity (from 3 x 10(-6) to 2 x 10(-5), and from 1.3 x 10(-4) to 0.6 x 10(-3), for the photon number and pulse energy, respectively) is close to the theoretical estimate for the parameters of the experiment.