Proton Probing Measurement of Electric and Magnetic Fields Generated by ns and ps Laser-Matter Interactions

The use of laser-accelerated protons as a particle probe for the detection of electric fields in plasmas has led in recent years to a wealth of novel information regarding the ultrafast plasma dynamics following high intensity laser-matter interactions. The high spatial quality and short duration of these beams have been essential to this purpose. We will discuss some of the most recent results obtained with this diagnostic at the Rutherford Appleton Laboratory (UK) and at LULI - Ecole Polytechnique (France), also applied to conditions of interest to conventional Inertial Confinement Fusion. In particular, the technique has been used to measure electric fields responsible for proton acceleration from solid targets irradiated with ps pulses, magnetic fields formed by ns pulse irradiation of solid targets, and electric fields associated with the ponderomotive channelling of ps laser pulses in under-dense plasmas.

Laser-Driven Proton Beams: Acceleration Mechanism, Beam Optimization, and Radiographic Applications

This paper reviews recent experimental activity in the area of optimization, control, and application of laser accelerated proton beams, carried out at the Rutherford Appleton Laboratory and the Laboratoire pour l’Utilisation des Lasers Intenses 100 TW facility in France. In particular, experiments have investigated the role of the scale length at the rear of the plasma in reducing target-normal-sheath-acceleration acceleration efficiency. Results match with recent theoretical predictions and provide information in view of the feasibility of proton fast-ignition applications. Experiments aiming to control the divergence of the proton beams have investigated the use of a laser-triggered microlens, which employs laser-driven transient electric fields in cylindrical geometry, enabling to focus the emitted
protons and select monochromatic beam lets out of the broad spectrum beam. This approach could be advantageous in view
of a variety of applications. The use of laser-driven protons as a particle probe for transient field detection has been developed and
applied to a number of experimental conditions. Recent work in this area has focused on the detection of large-scale self-generated magnetic fields in laser-produced plasmas and the investigation of fields associated to the propagation of relativistic electron both on the surface and in the bulk of targets irradiated by high-power laser pulses.

Stable GeV Ion Beam Acceleration from Thin Foils by Circularly Polarized Laser Pulses

A stable relativistic ion acceleration regime for thin foils irradiated by circularly polarized laser pulses is suggested. In this regime, the "light-sail" stage of radiation pressure acceleration for ions is smoothly connected with the initial relativistic "hole-boring" stage, and a defined relationship between laser intensity I(0), foil density n(0), and thickness l(0) should be satisfied. For foils with a wide range of n(0), the required I(0) and l(0) for the regime are theoretically estimated and verified with the particle-in-cell code ILLUMINATION. It is shown for the first time by 2D simulations that high-density monoenergetic ion beams with energy above GeV/u and divergence of 10 degrees are produced by circularly polarized lasers at intensities of 10(22) W/cm(2), which are within reach of current laser systems.

Time-dependent R -matrix theory for ultrafast atomic processes

We describe an ab initio nonperturbative time-dependent R-matrix theory for ultrafast atomic processes. This theory enables investigations of the interaction of few-femtosecond and -attosecond pulse lasers with complex multielectron atoms and atomic ions. A derivation and analysis of the basic equations are given, which propagate the atomic wave function in the presence of the laser field forward in time in the internal and external R-matrix regions. To verify the accuracy of the approach, we investigate two-photon ionization of Ne irradiated by an intense laser pulse and compare current results with those obtained using the R-matrix Floquet method and an alternative time-dependent method. We also verify the capability of the current approach by applying it to the study of two-dimensional momentum distributions of electrons ejected from Ne due to irradiation by a sequence of 2 as light pulses in the presence of a 780 nm laser field.

Presence of arsenic in agricultural products from arsenic-endemic areas and strategies to reduce arsenic intake in rural villages

About 100 million rural people in Asia are exposed to arsenic (As)-polluted drinking water and agricultural products. Total and inorganic arsenic (t-As and i-As) intake mainly depend on the quality of drinking and cooking waters, and amounts of seafood and rice consumed. The main problems occur in countries with poor water quality where the population depends on rice for their diet, and their t-As and i-As intake is high as a result of growing and cooking rice in contaminated water. Workable solutions to remove As from water and breeding rice cultivars with low As accumulation are being sought. In the meantime, simple recommendations for processing and cooking foods will help to reduce As intake. For instance, cooking using high volumes of As-free water may be a cheap way of reducing As exposure in rural populations. It is necessary to consider the effects of cooking and processing on t-As and i-As to obtain a realistic view of the risks associated with intake of As in Asendemic areas.

What role for DNA damage and repair in the bystander response?

The radiation-induced bystander effect challenges the accepted paradigm of direct DNA damage in response to energy deposition driving the biological consequences of radiation exposure. With the bystander response, cells which have not been directly exposed to radiation respond to their neighbours being targeted. In our own studies we have used novel targeted microbeam approaches to specifically irradiate parts of individual cells within a population to quantify the bystander response and obtain mechanistic information. Using this approach it has become clear that energy deposited by radiation in nuclear DNA is not required to trigger the effect, with cytoplasmic irradiation required. Irradiated cells also trigger a bystander response regardless of whether they themselves live or die, suggesting that the phenotype of the targeted cell is not a determining factor. Despite this however, a range of evidence has shown that repair status is important for dealing with the consequences of a bystander signal. Importantly, repair processes involved in the processing of dsb appear to be involved suggesting that the bystander response involves the delayed or indirect production of dsb-type lesions in bystander cells. Whether these are infact true dsb or complexes of oxidised bases in combination with strand breaks and the mechanisms for their formation, remains to be elucidated.

Gamma ray-induced bystander effect in tumour glioblastoma cells: a specific study on cell survival, cytokine release and cytokine receptors.

Recent experimental evidence has challenged the paradigm according to which radiation traversal through the nucleus of a cell is a prerequisite for producing genetic changes or biological responses. Thus, unexposed cells in the vicinity of directly irradiated cells or recipient cells of medium from irradiated cultures can also be affected. The aim of the present study was to evaluate, by means of the medium transfer technique, whether interleukin-8 and its receptor (CXCR1) may play a role in the bystander effect after gamma irradiation of T98G cells in vitro. In fact the cell specificity in inducing the bystander effect and in receiving the secreted signals that has been described suggests that not only the ability to release the cytokines but also the receptor profiles are likely to modulate the cell responses and the final outcome. The dose and time dependence of the cytokine release into the medium, quantified using an enzyme linked immunosorbent assay, showed that radiation causes alteration in the release of interleukin-8 from exposed cells in a dose-independent but time-dependent manner. The relative receptor expression was also affected in exposed and bystander cells.

The use of microbeams to investigate radiation damage in living cells.

The micro-irradiation technique continues to be highly relevant to a number of radiobiological studies in vitro. In particular, studies of the bystander effect show that direct damage to cells is not the only trigger for radiation-induced effects, but that unirradiated cells can also respond to signals from irradiated neighbours. Furthermore, the bystander response can be initiated even when no energy is deposited in the genomic DNA of the irradiated cell (i.e. by targeting just the cytoplasm).

Microbeam studies of the bystander response.

Microbeams have undergone a renaissance since their introduction and early use in the mid 60s. Recent advances in imaging, software and beam delivery have allowed rapid technological developments in microbeams for use in a range of experimental studies. The resurgence in the use of microbeams since the mid 90s has coincided with major changes in our understanding of how radiation interacts with cells. In particular, the evidence that bystander responses occur, where cells not directly irradiated can respond to irradiated neighbours, has brought about the evolution of new models of radiation response. Although these processes have been studied using a range of experimental approaches, microbeams offer a unique route by which bystander responses can be elucidated. Without exception, all of the microbeams currently active internationally have studied bystander responses in a range of cell and tissue models. Together these studies have considerably advanced our knowledge of bystander responses and the underpinning mechanisms. Much of this has come from charged particle microbeam studies, but increasingly, X-ray and electron microbeams are starting to contribute quantitative and mechanistic information on bystander effects. A recent development has been the move from studies with 2-D cell culture models to more complex 3-D systems where the possibilities of utilizing the unique characteristics of microbeams in terms of their spatial and temporal delivery will make a major impact.

Bystander effects induced by diffusing mediators after photodynamic stress.

The bystander effect, whereby cells that are not traversed by ionizing radiation exhibit various responses when in proximity to irradiated cells, is well documented in the field of radiation biology, Here we demonstrate that considerable bystander responses are also observed after photodynamic stress using the membrane-localizing dye deuteroporphyrin (DP). Using cells of a WTK1 human lymphoblastoid cell line in suspension and a transwell insert system that precludes contact between targeted and bystander cells, we have shown that the bystander signaling is mediated by diffusing species. The extranuclear localization of the photosensitizer used suggests that primary DNA damage is not the trigger for initiating these bystander responses, which include elevated oxidative stress, DNA damage (micronucleus formation), mutagenesis and decreased clonogenic survival. In addition, oxidative stress in the bystander population was reduced by the presence of the membrane antioxidant vitamin E in the targeted cells, suggesting that lipid peroxidation may play a key role in mediating these bystander effects. The fluence responses for these bystander effects are non-linear, with larger effects seen at lower fluences and toxicity to the target cell population. Hence, when considering outcomes of photodynamic action in cells and tissue, bystander effects may be significant, especially at sublethal fluences.

The 0.5M(J) transiting exoplanet WASP-13b

We report the discovery of WASP-13b, a low-mass M-p = 0.46(-0.05)(+0.06) M-J transiting exoplanet with an orbital period of 4.35298 +/- 0.00004 days. The transit has a depth of 9 mmag, and although our follow-up photometry does not allow us to constrain the impact parameter well (0 <b <0.46), with radius in the range R-p similar to 1.06-1.21 R-J the location of WASP-13b in the mass-radius plane is nevertheless consistent with H/He-dominated, irradiated, low core mass and core-free theoretical models. The G1V host star is similar to the Sun in mass (M-* = 1.03(-0.09)(+0.11) M-circle dot) and metallicity ([M/H] = 0.0 +/- 0.2), but is possibly older (8.5(-4.9)(+5.5) Gyr).

Coherent X-ray production via pulse reflection from laser-driven dense electron sheets

A scheme to obtain brilliant x-ray sources by coherent reflection of a counter-propagating pulse from laser-driven dense electron sheets is theoretically and numerically investigated in a self-consistent manner. A radiation pressure acceleration model for the dynamics of the electron sheets blown out from laser-irradiated ultrathin foils is developed and verified by PIC simulations. The first multidimensional and integral demonstration of the scheme by 2D PIC simulations is presented. It is found that the reflected pulse undergoes Doppler-upshift by a factor 4?z2, where ?z = (1- vz2/c2)-1/2 is the effective Lorentz factor of the electron sheet al ong its normal direction. Meanwhile the pulse electric field is intensified by a factor depending on the electron density of the sheet in its moving frame ne/?, where ? is the full Lorentz factor.

ATM acts downstream of ATR in the DNA damage response signaling of bystander cells.

This study identifies ataxia-telangiectasia mutated (ATM) as a further component of the complex signaling network of radiation-induced DNA damage in nontargeted bystander cells downstream of ataxia-telangiectasia and Rad3-related (ATR) and provides a rationale for molecular targeted modulation of these effects. In directly irradiated cells, ATR, ATM, and DNA-dependent protein kinase (DNA-PK) deficiency resulted in reduced cell survival as predicted by the known important role of these proteins in sensing DNA damage. A decrease in clonogenic survival was also observed in ATR/ATM/DNA-PK–proficient, nonirradiated bystander cells, but this effect was completely abrogated in ATR and ATM but not DNA-PK–deficient bystander cells. ATM activation in bystander cells was found to be dependent on ATR function. Furthermore, the induction and colocalization of ATR, 53BP1, ATM-S1981P, p21, and BRCA1 foci in nontargeted cells was shown, suggesting their involvement in bystander DNA damage signaling and providing additional potential targets for its modulation. 53BP1 bystander foci were induced in an ATR-dependent manner predominantly in S-phase cells, similar to ?H2AX foci induction. In conclusion, these results provide a rationale for the differential modulation of targeted and nontargeted effects of radiation.

New molecular targets in radiotherapy: DNA damage signalling and repair in targeted and non-targeted cells

Ionising radiation plays a key role in therapy due to its ability to directly induce DNA damage, in particular DNA double-strand breaks leading to cell death. Cells have multiple repair pathways which attempt to maintain genomic stability. DNA repair proteins have become key targets for therapy, using small molecule inhibitors, in combination with radiation and or chemotherapeutic agents as a means of enhancing cell killing. Significant advances in our understanding of the response of cells to radiation exposures has come from the observation of non-targeted effects where cells respond via mechanisms other than those which are a direct consequence of energy-dependent DNA damage. Typical of these is bystander signalling where cells respond to the fact that their neighbours have been irradiated. Bystander cells show a DNA damage response which is distinct from directly irradiated cells. In bystander cells, ATM- and Rad3-related (ATR) protein kinase-dependent signalling in response to stalled replication forks is an early event in the DNA damage response. The ATM protein kinase is activated downstream of ATR in bystander cells. This offers the potential for differential approaches for the modulation of bystander and direct effects with repair inhibitors which may impact on the response of tumours and on the protection of normal tissues during radiotherapy. (C) 2009 Elsevier B.V. All rights reserved.

Differential modulation of a radiation-induced bystander effect in glioblastoma cells by pifithrin-alpha and wortmannin

The implication of radiation-induced bystander effect (RIBE) for both radiation protection and radiotherapy has attracted significant attention, but a key question is how to modulate the RIBE. The present study found that, when a fraction of glioblastoma cells in T98G population were individually targeted with precise helium particles through their nucleus, micronucleus (MN) were induced and its yield increased non-linearly with radiation dose. After co-culturing with irradiated cells, additional MN could be induced in the non-irradiated bystander cells and its yield was independent of irradiation dose, giving direct evidence of a RIBE. Further results showed that the RIBE could be eliminated by pifithrin-alpha (p53 inhibitor) but enhanced by wortmannin (PI3K inhibitor). Moreover, it was found that nitric oxide (NO) contributed to this RIBE, and the levels of NO of both irradiated cells and bystander cells could be extensively diminished by pifithrin-alpha but insignificantly reduced by wortmannin. Our results indicate that RIBE can be modulated by p53 and PI3K through a NO-dependent and NO-independent pathway, respectively. (C) 2009 Elsevier B.V. All rights reserved.