Dispersion calibration for the National Ignition Facility electron-positron-proton spectrometers for intense laser matter interactions.

Electron-positron pairs, produced in intense laser-solid interactions, are diagnosed using magnetic spectrometers with image plates, such as the National Ignition Facility Electron-Positron-Proton Spectrometers (EPPSs). Although modeling can help infer the quantitative value, the accuracy of the models needs to be verified to ensure measurement quality. The dispersion of low-energy electrons and positrons may be affected by fringe magnetic fields near the entrance of the EPPS. We have calibrated the EPPS with six electron beams from a Siemens Oncor linear accelerator (linac) ranging in energy from 2.7 MeV to 15.2 MeV as they enter the spectrometer. A Geant4 traveling-wave optical parametric amplifier of superfluorescence Monte Carlo simulation was set up to match depth dose curves and lateral profiles measured in water at 100 cm source-surface distance. An accurate relationship was established between the bending magnet current setting and the energy of the electron beam at the exit window. The simulations and measurements were used to determine the energy distributions of the six electron beams at the EPPS slit. Analysis of the scanned image plates together with the determined energy distribution arriving in the spectrometer provides improved dispersion curves for the EPPS.

Electron-Nanobunch-Width-Dominated Spectral Power Law for Relativistic Harmonic Generation from Ultrathin Foils.

Relativistic high-order harmonic generation from solid-density plasma offers a compact source of coherent ultraviolet and x-ray light. For solid targets much thinner than the laser wavelength, the plasma thickness can be tuned to increase conversion efficiency; a reduction in total charge allows for balancing the laser and plasma driving forces, producing the most effective interaction. Unlike for semi-infinite plasma surfaces, we find that for ultrathin foil targets the dominant factor in the emission spectral shape is the finite width of the electron nanobunches, leading to a power-law exponent of approximately 10/3. Ultrathin foils produce higher-efficiency frequency conversion than solid targets for moderately relativistic (1

The X-Ray Emission Effectiveness of Plasma Mirrors: Reexamining Power-Law Scaling for Relativistic High-Order Harmonic Generation.

Ultrashort pulsed lasers provide uniquely detailed access to the ultrafast dynamics of physical, chemical, and biological systems, but only a handful of wavelengths are directly produced by solid-state lasers, necessitating efficient high-power frequency conversion. Relativistic plasma mirrors generate broadband power-law spectra, that may span the gap between petawatt-class infrared laser facilities and x-ray free-electron lasers; despite substantial theoretical work the ultimate efficiency of this relativistic high-order-harmonic generation remains unclear. We show that the coherent radiation emitted by plasma mirrors follows a power-law distribution of energy over frequency with an exponent that, even in the ultrarelativistic limit, strongly depends on the ratio of laser intensity to plasma density and exceeds the frequently quoted value of  -8/3 over a wide range of parameters. The coherent synchrotron emission model, when adequately corrected for the finite width of emitting electron bunches, is not just valid for p-polarized light and thin foil targets, but generally describes relativistic harmonic generation, including at normal incidence and with finite-gradient plasmas. Our numerical results support the ω-4/3 scaling of the synchrotron emission model as a limiting efficiency of the process under most conditions. The highest frequencies that can be generated with this scaling are usually restricted by the width of the emitting electron bunch rather than the Lorentz factor of the fastest electrons. The theoretical scaling relations developed here suggest, for example, that with a 20-PW 800-nm driving laser, 1 TW/harmonic can be produced for 1-keV photons.

Laser Amplification in Strongly Magnetized Plasma.

We consider backscattering of laser pulses in strongly magnetized plasma mediated by kinetic magnetohydrodynamic waves. Magnetized low-frequency (MLF) scattering, which can occur when the external magnetic field is neither perpendicular nor parallel to the laser propagation direction, provides an instability growth rate higher than Raman scattering and a frequency downshift comparable to Brillouin scattering. In addition to the high growth rate, which allows smaller plasmas, and the 0.1%-2% frequency downshift, which permits a wide range of pump sources, MLF scattering is an ideal candidate for amplification because the process supports an exceptionally large bandwidth, which particle-in-cell simulations show produces ultrashort durations. Under some conditions, MLF scattering also becomes the dominant spontaneous backscatter instability, with implications for magnetized laser-confinement experiments.

Theory of electromagnetic wave frequency upconversion in dynamic media.

Frequency upconversion of an electromagnetic wave can occur in ionized plasma with decreasing electric permittivity and in split-ring resonator-structure metamaterials with decreasing magnetic permeability. We develop a general theory to describe the evolution of the wave frequency, amplitude, and energy density in homogeneous media with a temporally decreasing refractive index. We find that upconversion of the wave frequency is necessarily accompanied by partitioning of the wave energy into low-frequency modes, which sets an upper limit on the energy conversion efficiency. The efficiency limits are obtained for both varying permittivity and varying permeability.

X-ray amplification by stimulated Brillouin scattering.

Plasma-based parametric amplification using stimulated Brillouin scattering offers a route to coherent x-ray pulses orders of magnitude more intense than those of the brightest available sources. Brillouin amplification permits amplification of shorter wavelengths with lower pump intensities than Raman amplification, which Landau and collisional damping limit in the x-ray regime. Analytic predictions, numerical solutions of the three-wave-coupling equations, and particle-in-cell simulations suggest that Brillouin amplification in solid-density plasmas will allow compression of current x-ray free-electron laser pulses to subfemtosecond durations and unprecedented intensities.

Waveform-Controlled Relativistic High-Order-Harmonic Generation.

We consider the efficiency limit of relativistic high-order-harmonic emission from solid targets achievable with tailored light fields. Using one-dimensional particle-in-cell simulations, the maximum energy conversion efficiency is shown to reach as high as 10% for the harmonics in the range of 80-200 eV and is largely independent of laser intensity and plasma density. The waveforms most effective at driving harmonics have a broad spectrum with a lower-frequency limit set by the width of the incident pulse envelope and an upper limit set by the relativistic plasma frequency.

Strongly Enhanced Stimulated Brillouin Backscattering in an Electron-Positron Plasma.

Stimulated Brillouin backscattering of light is shown to be drastically enhanced in electron-positron plasmas, in contrast to the suppression of stimulated Raman scattering. A generalized theory of three-wave coupling between electromagnetic and plasma waves in two-species plasmas with arbitrary mass ratios, confirmed with a comprehensive set of particle-in-cell simulations, reveals violations of commonly held assumptions about the behavior of electron-positron plasmas. Specifically, in the electron-positron limit three-wave parametric interaction between light and the plasma acoustic wave can occur, and the acoustic wave phase velocity differs from its usually assumed value.

New diagnostic methods for laser plasma- and microwave-enhanced combustion.

The study of pulsed laser- and microwave-induced plasma interactions with atmospheric and higher pressure combusting gases requires rapid diagnostic methods that are capable of determining the mechanisms by which these interactions are taking place. New rapid diagnostics are presented here extending the capabilities of Rayleigh and Thomson scattering and resonance-enhanced multi-photon ionization (REMPI) detection and introducing femtosecond laser-induced velocity and temperature profile imaging. Spectrally filtered Rayleigh scattering provides a method for the planar imaging of temperature fields for constant pressure interactions and line imaging of velocity, temperature and density profiles. Depolarization of Rayleigh scattering provides a measure of the dissociation fraction, and multi-wavelength line imaging enables the separation of Thomson scattering from Rayleigh scattering. Radar REMPI takes advantage of high-frequency microwave scattering from the region of laser-selected species ionization to extend REMPI to atmospheric pressures and implement it as a stand-off detection method for atomic and molecular species in combusting environments. Femtosecond laser electronic excitation tagging (FLEET) generates highly excited molecular species and dissociation through the focal zone of the laser. The prompt fluorescence from excited molecular species yields temperature profiles, and the delayed fluorescence from recombining atomic fragments yields velocity profiles.

Enhanced attosecond bursts of relativistic high-order harmonics driven by two-color fields.

We study the generation of attosecond x-ray and ultraviolet pulses from relativistically driven overdense plasma targets with two-color incident light. Particle-in-cell simulations show that significant improvement in pulse intensity and isolation is achievable with appropriate laser and plasma parameters. Conversion of 5% of incident laser energy to its second harmonic can enhance the intensity of generated attosecond pulses by an order of magnitude. This approach allows the generation of higher attosecond pulse intensities with existing experimental laser technology and offers a powerful tool for the analysis of the dynamics of relativistic laser-plasma interaction.

Analytical modeling and experimental characterization of chemotaxis in Serratia marcescens.

This paper presents a modeling and experimental framework to characterize the chemotaxis of Serratia marcescens (S. marcescens) relying on two-dimensional and three-dimensional tracking of individual bacteria. Previous studies mainly characterized bacterial chemotaxis based on population density analysis. Instead, this study focuses on single-cell tracking and measuring the chemotactic drift velocity V(C) from the biased tumble rate of individual bacteria on exposure to a concentration gradient of l-aspartate. The chemotactic response of S. marcescens is quantified over a range of concentration gradients (10^{-3} to 5 mM/mm) and average concentrations (0.5 × 10(-3) to 2.5 mM). Through the analysis of a large number of bacterial swimming trajectories, the tumble rate is found to have a significant bias with respect to the swimming direction. We also verify the relative gradient sensing mechanism in the chemotaxis of S. marcescens by measuring the change of V(C) with the average concentration and the gradient. The applied full pathway model with fitted parameters matches the experimental data. Finally, we show that our measurements based on individual bacteria lead to the determination of the motility coefficient µ (7.25 × 10(-6) cm(2)/s) of a population. The experimental characterization and simulation results for the chemotaxis of this bacterial species contribute towards using S. marcescens in chemically controlled biohybrid systems.

Magnetic steering control of multi-cellular bio-hybrid microswimmers.

Bio-hybrid devices, which integrate biological cells with synthetic components, have opened a new path in miniaturized systems with the potential to provide actuation and control for systems down to a few microns in size. Here, we address the challenge of remotely controlling bio-hybrid microswimmers propelled by multiple bacterial cells. These devices have been proposed as a viable method for targeted drug delivery but have also been shown to exhibit stochastic motion. We demonstrate a method of remote magnetic control that significantly reduces the stochasticity of the motion, enabling steering control. The demonstrated microswimmers consist of multiple Serratia marcescens (S. marcescens) bacteria attached to a 6 µm-diameter superparamagnetic bead. We characterize their motion and define the parameters governing their controllability. We show that the microswimmers can be controlled along two-dimensional (2-D) trajectories using weak magnetic fields (≤10 mT) and can achieve 2-D swimming speeds up to 7.3 µm s(-1). This magnetic steering approach can be integrated with sensory-based steering in future work, enabling new control strategies for bio-hybrid microsystems.

Influence of magnetic fields on magneto-aerotaxis.

The response of cells to changes in their physico-chemical micro-environment is essential to their survival. For example, bacterial magnetotaxis uses the Earth's magnetic field together with chemical sensing to help microorganisms move towards favoured habitats. The studies of such complex responses are lacking a method that permits the simultaneous mapping of the chemical environment and the response of the organisms, and the ability to generate a controlled physiological magnetic field. We have thus developed a multi-modal microscopy platform that fulfils these requirements. Using simultaneous fluorescence and high-speed imaging in conjunction with diffusion and aerotactic models, we characterized the magneto-aerotaxis of Magnetospirillum gryphiswaldense. We assessed the influence of the magnetic field (orientation; strength) on the formation and the dynamic of a micro-aerotactic band (size, dynamic, position). As previously described by models of magnetotaxis, the application of a magnetic field pointing towards the anoxic zone of an oxygen gradient results in an enhanced aerotaxis even down to Earth's magnetic field strength. We found that neither a ten-fold increase of the field strength nor a tilt of 45° resulted in a significant change of the aerotactic efficiency. However, when the field strength is zeroed or when the field angle is tilted to 90°, the magneto-aerotaxis efficiency is drastically reduced. The classical model of magneto-aerotaxis assumes a response proportional to the cosine of the angle difference between the directions of the oxygen gradient and that of the magnetic field. Our experimental evidence however shows that this behaviour is more complex than assumed in this model, thus opening up new avenues for research.

Femtosecond laser electronic excitation tagging for quantitative velocity imaging in air.

Time-accurate velocity measurements in unseeded air are made by tagging nitrogen with a femtosecond-duration laser pulse and monitoring the displacement of the molecules with a time-delayed, fast-gated camera. Centimeter-long lines are written through the focal region of a ∼1 mJ, 810 nm laser and are produced by nonlinear excitation and dissociation of nitrogen. Negligible heating is associated with this interaction. The emission arises from recombining nitrogen atoms and lasts for tens of microseconds in natural air. It falls into the 560 to 660 nm spectral region and consists of multiple spectral lines associated with first positive nitrogen transitions. The feasibility of this concept is demonstrated with lines written across a free jet, yielding instantaneous and averaged velocity profiles. The use of high-intensity femtosecond pulses for flow tagging allows the accurate determination of velocity profiles with a single laser system and camera.

HMGB1 mediates endogenous TLR2 activation and brain tumor regression.

BACKGROUND: Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor that carries a 5-y survival rate of 5%. Attempts at eliciting a clinically relevant anti-GBM immune response in brain tumor patients have met with limited success, which is due to brain immune privilege, tumor immune evasion, and a paucity of dendritic cells (DCs) within the central nervous system. Herein we uncovered a novel pathway for the activation of an effective anti-GBM immune response mediated by high-mobility-group box 1 (HMGB1), an alarmin protein released from dying tumor cells, which acts as an endogenous ligand for Toll-like receptor 2 (TLR2) signaling on bone marrow-derived GBM-infiltrating DCs. METHODS AND FINDINGS: Using a combined immunotherapy/conditional cytotoxic approach that utilizes adenoviral vectors (Ad) expressing Fms-like tyrosine kinase 3 ligand (Flt3L) and thymidine kinase (TK) delivered into the tumor mass, we demonstrated that CD4(+) and CD8(+) T cells were required for tumor regression and immunological memory. Increased numbers of bone marrow-derived, tumor-infiltrating myeloid DCs (mDCs) were observed in response to the therapy. Infiltration of mDCs into the GBM, clonal expansion of antitumor T cells, and induction of an effective anti-GBM immune response were TLR2 dependent. We then proceeded to identify the endogenous ligand responsible for TLR2 signaling on tumor-infiltrating mDCs. We demonstrated that HMGB1 was released from dying tumor cells, in response to Ad-TK (+ gancyclovir [GCV]) treatment. Increased levels of HMGB1 were also detected in the serum of tumor-bearing Ad-Flt3L/Ad-TK (+GCV)-treated mice. Specific activation of TLR2 signaling was induced by supernatants from Ad-TK (+GCV)-treated GBM cells; this activation was blocked by glycyrrhizin (a specific HMGB1 inhibitor) or with antibodies to HMGB1. HMGB1 was also released from melanoma, small cell lung carcinoma, and glioma cells treated with radiation or temozolomide. Administration of either glycyrrhizin or anti-HMGB1 immunoglobulins to tumor-bearing Ad-Flt3L and Ad-TK treated mice, abolished therapeutic efficacy, highlighting the critical role played by HMGB1-mediated TLR2 signaling to elicit tumor regression. Therapeutic efficacy of Ad-Flt3L and Ad-TK (+GCV) treatment was demonstrated in a second glioma model and in an intracranial melanoma model with concomitant increases in the levels of circulating HMGB1. CONCLUSIONS: Our data provide evidence for the molecular and cellular mechanisms that support the rationale for the clinical implementation of antibrain cancer immunotherapies in combination with tumor killing approaches in order to elicit effective antitumor immune responses, and thus, will impact clinical neuro-oncology practice.