Cell survival responses after exposure to modulated radiation fields.

In the present study survival responses were determined in cells with differing radiosensitivity, specifically primary fibroblast (AG0-1522B), human breast cancer (MDA-MB-231), human prostate cancer (DU-145) and human glioma (T98G) cells, after exposure to modulated radiation fields delivered by shielding 50% of the tissue culture flask. A significant decrease (P < 0.05) in cell survival was observed in the shielded area, outside the primary treatment field (out-of-field), that was lower than predicted when compared to uniform exposures fitted to the linear-quadratic model. Cellular radiosensitivity was demonstrated to be an important factor in the level of response for both the in- and out-of-field regions. These responses were shown to be dependent on secretion-mediated intercellular communication, because inhibition of cellular secreted factors between the in- and out-of-field regions abrogated the response. Out-of-field cell survival was shown to increase after pretreatment of cells with agents known to inhibit factors involved in mediating radiation-induced bystander signaling (aminoguanidine, DMSO or cPTIO). These data illustrate a significant decrease in survival out-of-field, dependent upon intercellular communication, in several cell lines with varying radiosensitivity after exposure to a modulated radiation field. This study provides further evidence for the importance of intercellular signaling in modulated exposures, where dose gradients are present, and may inform the refinement of established radiobiological models to facilitate the optimization of advanced radiotherapy treatment plans.

The VLT-FLAMES survey of massive stars: observations centered on the Magellanic Cloud clusters NGC 330, NGC 346, NGC 2004, and the N11 region

We present new observations of 470 stars using the Fibre Large Array Multi-Element Spectrograph ( FLAMES) instrument in fields centered on the clusters NGC330 and NGC346 in the Small Magellanic Cloud (SMC), and NGC2004 and the N11 region in the Large Magellanic Cloud (LMC). A further 14 stars were observed in the N11 and NGC330 fields using the Ultraviolet and Visual Echelle Spectrograph (UVES) for a separate programme. Spectral classifications and stellar radial velocities are given for each target, with careful attention to checks for binarity. In particular, we have investigated previously unexplored regions around the central LH9/LH10 complex of N11, finding similar to 25 new O-type stars from our spectroscopy. We have observed a relatively large number of Be-type stars that display permitted Fe II emission lines. These are primarily not in the cluster cores and appear to be associated with classical Be-type stars, rather than pre main-sequence objects. The presence of the Fe II emission, as compared to the equivalent width of Ha, is not obviously dependent on metallicity. We have also explored the relative fraction of Be- to normal B-type stars in the field-regions near to NGC330 and NGC2004, finding no strong evidence of a trend with metallicity when compared to Galactic results. A consequence of service observations is that we have reasonable time-sampling in three of our FLAMES fields. We find lower limits to the binary fraction of O- and early B-type stars of 23 to 36%. One of our targets (NGC346-013) is especially interesting with a massive, apparently hotter, less luminous secondary component.

Spectral modification of laser-accelerated proton beams by self-generated magnetic fields

Target normal measurements of proton energy spectra from ultrathin (50-200 nm) planar foil targets irradiated by 10(19) W cm(-2) 40 fs laser pulses exhibit broad maxima that are not present in the energy spectra from micron thickness targets (6 mu m). The proton flux in the peak is considerably greater than the proton flux observed in the same energy range in thicker targets. Numerical modelling of the experiment indicates that this spectral modification in thin targets is caused by magnetic fields that grow at the rear of the target during the laser-target interaction.

Temporally and spatially resolved measurements of multi-megagauss magnetic fields in high intensity laser-produced plasmas

We report spatially and temporally resolved measurements of self-generated multi-megagauss magnetic fields produced during ultrahigh intensity laser plasma interactions. Spatially resolved measurements of the magnetic fields show an asymmetry in the distribution of field with respect to the angle of laser incidence. Temporally resolved measurements of the self-generated third harmonic suggest that the strength of the magnetic field is proportional to the square root of laser intensity (i.e., the laser B-field) during the rise of the laser pulse. The experimental results are compared with numerical simulations using a particle-in-cell code which also shows clear asymmetry of the field profile and similar magnetic field growth rates and scalings.

Lateral electron transport in high-intensity laser-irradiated foils diagnosed by ion emission

An experimental investigation of lateral electron transport in thin metallic foil targets irradiated by ultraintense (>= 10(19) W/cm(2)) laser pulses is reported. Two-dimensional spatially resolved ion emission measurements are used to quantify electric-field generation resulting from electron transport. The measurement of large electric fields (similar to 0.1 TV/m) millimeters from the laser focus reveals that lateral energy transport continues long after the laser pulse has decayed. Numerical simulations confirm a very strong enhancement of electron density and electric field at the edges of the target.

Laboratory measurements of 0.7 GG magnetic fields generated during high-intensity laser interactions with dense plasmas

We report measurements of ultrahigh magnetic fields produced during intense (similar to10(20) Wcm(-2) mum(2)) laser interaction experiments with solids. We show that polarization measurements of high-order vuv laser harmonics generated during the interaction (up to the 15th order) suggest the existence of magnetic field strengths of 0.7+/-0.1 GG in the overdense plasma. Measurements using higher order harmonics indicate that denser regions of the plasma can be probed. This technique may be useful for measurements of multi-GG level magnetic fields which are predicted to occur at even higher intensities.

A computational model of cellular response to modulated radiation fields

Purpose:
To develop a model to describe the response of cell populations to spatially modulated radiation exposures of relevance to advanced radiotherapies.

Materials and Methods:
A Monte Carlo model of cellular radiation response was developed. This model incorporated damage from both direct radiation and intercellular communication including bystander signaling. The predictions of this model were compared to previously measured survival curves for a normal human fibroblast line (AGO1522) and prostate tumor cells (DU145) exposed to spatially modulated fields.

Results:
The model was found to be able to accurately reproduce cell survival both in populations which were directly exposed to radiation and those which were outside the primary treatment field. The model predicts that the bystander effect makes a significant contribution to cell killing even in uniformly irradiated cells. The bystander effect contribution varies strongly with dose, falling from a high of 80% at low doses to 25% and 50% at 4 Gy for AGO1522 and DU145 cells, respectively. This was verified using the inducible nitric oxide synthase inhibitor aminoguanidine to inhibit the bystander effect in cells exposed to different doses, which showed significantly larger reductions in cell killing at lower doses.

Conclusions:
The model presented in this work accurately reproduces cell survival following modulated radiation exposures, both in and out of the primary treatment field, by incorporating a bystander component. In addition, the model suggests that the bystander effect is responsible for a significant portion of cell killing in uniformly irradiated cells, 50% and 70% at doses of 2 Gy in AGO1522 and DU145 cells, respectively. This description is a significant departure from accepted radiobiological models and may have a significant impact on optimization of treatment planning approaches if proven to be applicable in vivo.

Weibel-induced filamentation during an ultrafast, laser-driven plasma expansion

The development of current instabilities behind the front of a cylindrically expanding plasma has been investigated experimentally via proton probing techniques. A multitude of tubelike filamentary structures is observed to form behind the front of a plasma created by irradiating solid-density wire targets with a high-intensity (I~1019??W/cm2), picosecond-duration laser pulse. These filaments exhibit a remarkable degree of stability, persisting for several tens of picoseconds, and appear to be magnetized over a filament length corresponding to several filament radii. Particle-in-cell simulations indicate that their formation can be attributed to a Weibel instability driven by a thermal anisotropy of the electron population. We suggest that these results may have implications in astrophysical scenarios, particularly concerning the problem of the generation of strong, spatially extended and sustained magnetic fields in astrophysical jets.

Large quasistatic magnetic fields generated by a relativistically intense laser pulse propagating in a preionized plasma

Two spatially separated toroidal magnetic fields in the megagauss range have been detected with Faraday rotation during and after propagation of a relativistically intense laser pulse through preionized plasmas. Besides a field in the outer region of the plasma oriented as a conventional thermoelectric field, a field with the opposite orientation closely surrounding the propagation axis is observed, in conditions under which relativistic channeling occurs. A 3D particle-in-cell code was used to simulate the interaction under the conditions of the experiment.