Chemical-vapor deposited ultra-fast diamond detectors for temporal measurements of ion bunches.

This article reports on the development of thin diamond detectors and their characterization for their application in temporal profile measurements of subnanosecond ion bunches. Two types of diamonds were used: a 20 µm thin polycrystalline chemical vapor deposited (CVD) diamond and a membrane with a thickness of (5 ± 1) µm etched out of a single crystal (sc) CVD diamond. The combination of a small detector electrode and an impedance matched signal outlet leads to excellent time response properties with a signal pulse resolution (FWHM) of τ = (113 ± 11) ps. Such a fast diamond detector is a perfect device for the time of flight measurements of MeV ions with bunch durations in the subnanosecond regime. The scCVD diamond membrane detector was successfully implemented within the framework of the laser ion generation handling and transport project, in which ion beams are accelerated via a laser-driven source and shaped with conventional accelerator technology. The detector was used to measure subnanosecond proton bunches with an intensity of 108 protons per bunch.

CVD diamond detector with interdigitated electrode pattern for time-of-flight energy-loss measurements of low-energy ion bunches.

Ion stopping experiments in plasma for beam energies of few hundred keV per nucleon are of great interest to benchmark the stopping-power models in the context of inertial confinement fusion and high-energy-density physics research. For this purpose, a specific ion detector on chemical-vapor-deposition diamond basis has been developed for precise time-of-flight measurements of the ion energy loss. The electrode structure is interdigitated for maximizing its sensitivity to low-energy ions, and it has a finger width of 100 µm and a spacing of 500 µm. A short single α-particle response is obtained, with signals as narrow as 700 ps at full width at half maximum. The detector has been tested with α-particle bunches at a 500 keV per nucleon energy, showing an excellent time-of-flight resolution down to 20 ps. In this way, beam energy resolutions from 0.4 keV to a few keV have been obtained in an experimental configuration using a 100 µg/cm2 thick carbon foil as an energy-loss target and a 2 m time-of-flight distance. This allows a highly precise beam energy measurement of δE/E ≈ 0.04%-0.2% and a resolution on the energy loss of 0.6%-2.5% for a fine testing of stopping-power models.

PO and ID BCG vaccination in humans induce distinct mucosal and systemic immune responses and CD4+ T cell transcriptomal molecular signatures.

Protective efficacy of Bacillus Calmette-Guérin (BCG) may be affected by the methods and routes of vaccine administration. We have studied the safety and immunogenicity of oral (PO) and/or intradermal (ID) administration of BCG in healthy human subjects. No major safety concerns were detected in the 68 healthy adults vaccinated with PO and/or ID BCG. Although both PO and ID BCG could induce systemic Th1 responses capable of IFN-γ production, ID BCG more strongly induced systemic Th1 responses. In contrast, stronger mucosal responses (TB-specific secretory IgA and bronchoalveolar lavage T cells) were induced by PO BCG vaccination. To generate preliminary data comparing the early gene signatures induced by mucosal and systemic BCG vaccination, CD4+ memory T cells were isolated from subsets of BCG vaccinated subjects pre- (Day 0) and post-vaccination (Days 7 and 56), rested or stimulated with BCG infected dendritic cells, and then studied by Illumina BeadArray transcriptomal analysis. Notably, distinct gene expression profiles were identified both on Day 7 and Day 56 comparing the PO and ID BCG vaccinated groups by GSEA analysis. Future correlation analyses between specific gene expression patterns and distinct mucosal and systemic immune responses induced will be highly informative for TB vaccine development.

Determination of Hydrogen Density by Swift Heavy Ions.

A novel method to determine the total hydrogen density and, accordingly, a precise plasma temperature in a lowly ionized hydrogen plasma is described. The key to the method is to analyze the energy loss of swift heavy ions interacting with the respective bound and free electrons of the plasma. A slowly developing and lowly ionized hydrogen theta-pinch plasma is prepared. A Boltzmann plot of the hydrogen Balmer series and the Stark broadening of the H_{ß} line preliminarily defines the plasma with a free electron density of (1.9±0.1)×10^{16} cm^{-3} and a free electron temperature of 0.8-1.3 eV. The temperature uncertainty results in a wide hydrogen density, ranging from 2.3×10^{16} to 7.8×10^{18} cm^{-3}. A 108 MHz pulsed beam of ^{48}Ca^{10+} with a velocity of 3.652 MeV/u is used as a probe to measure the total energy loss of the beam ions. Subtracting the calculated energy loss due to free electrons, the energy loss due to bound electrons is obtained, which linearly depends on the bound electron density. The total hydrogen density is thus determined as (1.9±0.7)×10^{17} cm^{-3}, and the free electron temperature can be precisely derived as 1.01±0.04 eV. This method should prove useful in many studies, e.g., inertial confinement fusion or warm dense matter.

Experimental discrimination of ion stopping models near the Bragg peak in highly ionized matter.

The energy deposition of ions in dense plasmas is a key process in inertial confinement fusion that determines the α-particle heating expected to trigger a burn wave in the hydrogen pellet and resulting in high thermonuclear gain. However, measurements of ion stopping in plasmas are scarce and mostly restricted to high ion velocities where theory agrees with the data. Here, we report experimental data at low projectile velocities near the Bragg peak, where the stopping force reaches its maximum. This parameter range features the largest theoretical uncertainties and conclusive data are missing until today. The precision of our measurements, combined with a reliable knowledge of the plasma parameters, allows to disprove several standard models for the stopping power for beam velocities typically encountered in inertial fusion. On the other hand, our data support theories that include a detailed treatment of strong ion-electron collisions.

Temperature measurement of hohlraum radiation for energy loss experiments in indirectly laser heated carbon plasma.

For ion energy loss measurements in plasmas with near solid densities, an indirect laser heating scheme for carbon foils has been developed at GSI Helmholtzzentrum für Schwerionenforschung GmbH (Darmstadt, Germany). To achieve an electron density of 10^{22}cm^{3} and an electron temperature of 10-30eV, two carbon foils with an areal density of 100µg/cm^{2} heated in a double-hohlraum configuration have been chosen. In this paper we present the results of temperature measurements of both primary and secondary hohlraums for two different hohlraum designs. They were heated by the PHELIX laser with a wavelength of 527nm and an energy of 150J in 1.5ns. For this purpose the temperature has been investigated by an x-ray streak camera with a transmission grating as the dispersive element.

Predictions for the energy loss of light ions in laser-generated plasmas at low and medium velocities.

The energy loss of light ions in dense plasmas is investigated with special focus on low to medium projectile energies, i.e., at velocities where the maximum of the stopping power occurs. In this region, exceptionally large theoretical uncertainties remain and no conclusive experimental data are available. We perform simulations of beam-plasma configurations well suited for an experimental test of ion energy loss in highly ionized, laser-generated carbon plasmas. The plasma parameters are extracted from two-dimensional hydrodynamic simulations, and a Monte Carlo calculation of the charge-state distribution of the projectile ion beam determines the dynamics of the ion charge state over the whole plasma profile. We show that the discrepancies in the energy loss predicted by different theoretical models are as high as 20-30%, making these theories well distinguishable in suitable experiments.

Role of charge transfer in heavy-ion-beam-plasma interactions at intermediate energies.

In this paper we investigate the influence of the plasma properties on the charge state distribution of a swift heavy ion beam interacting with a plasma. The main finding is that the charge state in plasma can be lower than in cold matter. The charge state distribution is determined by the ionization and recombination rates which are balancing each other out. Both, ionization and recombination rates, as well as atomic excitation and decay rates, depend on the plasma parameters in different ways. These effects have been theoretically studied by Monte Carlo simulations on the example of an argon ion beam at an energy of 4MeV/u in a carbon plasma. This study covers a plasma parameter space ranging from ion densities from 10(18) to 10(23) cm(-3) and electron temperatures from 10 to 200 eV.

Severe hypophosphataemia after intravenous iron administration.

Currently, in many centres, intravenous administration of iron is becoming increasingly popular because of higher efficacy and decreased side effects, mainly gastrointestinal, compared with oral iron therapy. Studies of intravenous ferric carboxymaltose administration in the postpartum setting and in patients with non-dialysis-dependent chronic kidney disease revealed a decrease in serum phosphate levels that was generally asymptomatic and transient. Here, we report four cases of severe and symptomatic hypophosphataemia after intravenous iron administration. All patients received this as therapy for iron deficiency anaemia due to heavy menstrual bleeding. In most cases, a pre-existent disorder in the phosphate homeostasis existed, such as a secondary (cases 3 and 4) or tertiary hyperparathyroidism (case 1). However, in the second case there were no risk factors for a dysregulation of the phosphate homeostasis. Based on these findings, we conclude that severe and symptomatic hypophosphatemia can occur as a side effect of intravenous iron administration and can persist for months after administration. Especially patients with low phosphate levels prior to therapy due to concomitant disorders in phosphate homeostasis (e.g. hyperparathyroidism, vitamin D deficiency) are at risk.

Probing the complex ion structure in liquid carbon at 100 GPa.

We present the first direct experimental test of the complex ion structure in liquid carbon at pressures around 100 GPa, using spectrally resolved x-ray scattering from shock-compressed graphite samples. Our results confirm the structure predicted by ab initio quantum simulations and demonstrate the importance of chemical bonds at extreme conditions similar to those found in the interiors of giant planets. The evidence presented here thus provides a firmer ground for modeling the evolution and current structure of carbon-bearing icy giants like Neptune, Uranus, and a number of extrasolar planets.

Energy loss and charge transfer of argon in a laser-generated carbon plasma.

This Letter reports on the measurement of the energy loss and the projectile charge states of argon ions at an energy of 4 MeV/u penetrating a fully ionized carbon plasma. The plasma of n(e)≈10(20) cm(-3) and T(e)≈180 eV is created by two laser beams at λ(Las)=532 nm incident from opposite sides on a thin carbon foil. The resulting plasma is spatially homogenous and allows us to record precise experimental data. The data show an increase of a factor of 2 in the stopping power which is in very good agreement with a specifically developed Monte Carlo code, that allows the calculation of the heavy ion beam's charge state distribution and its energy loss in the plasma.

Development of a Nomarski-type multi-frame interferometer as a time and space resolving diagnostics for the free electron density of laser-generated plasma.

This article reports on the development and set-up of a Nomarski-type multi-frame interferometer as a time and space resolving diagnostics of the free electron density in laser-generated plasma. The interferometer allows the recording of a series of 4 images within 6 ns of a single laser-plasma interaction. For the setup presented here, the minimal accessible free electron density is 5 × 10(18) cm(-3), the maximal one is 2 × 10(20) cm(-3). Furthermore, it provides a resolution of the electron density in space of 50 µm and in time of 0.5 ns for one image with a customizable magnification in space for each of the 4 images. The electron density was evaluated from the interferograms using an Abel inversion algorithm. The functionality of the system was proven during first experiments and the experimental results are presented and discussed. A ray tracing procedure was realized to verify the interferometry pictures taken. In particular, the experimental results are compared to simulations and show excellent agreement, providing a conclusive picture of the evolution of the electron density distribution.

Time- and spectrally resolved measurements of laser-driven hohlraum radiation.

At the GSI Helmholtz center for heavy-ion research combined experiments with heavy ions and laser-produced plasmas are investigated. As a preparation to utilize indirectly heated targets, where a converter hohlraum provides thermal radiation to create a more homogeneous plasma, this converter target has to be characterized. In this paper the latest results of these measurements are presented. Small spherical cavities with diameters between 600 and 750 µm were heated with laser energies up to 30 J at 532-nm wavelength. Radiation temperatures could be determined by time-resolved as well as time-integrated diagnostics, and maximum values of up to 35 eV were achieved.

Energy loss of argon in a laser-generated carbon plasma.

The experimental data presented in this paper address the energy loss determination for argon at 4 MeV/u projectile energy in laser-generated carbon plasma covering a huge parameter range in density and temperature. Furthermore, a consistent theoretical description of the projectile charge state evolution via a Monte Carlo code is combined with an improved version of the CasP code that allows us to calculate the contributions to the stopping power of bound and free electrons for each projectile charge state. This approach gets rid of any effective charge description of the stopping power. Comparison of experimental data and theoretical results allows us to judge the influence of different plasma parameters.

Radiochromic film imaging spectroscopy of laser-accelerated proton beams.

This article reports on an experimental method to fully reconstruct laser-accelerated proton beam parameters called radiochromic film imaging spectroscopy (RIS). RIS allows for the characterization of proton beams concerning real and virtual source size, envelope- and microdivergence, normalized transverse emittance, phase space, and proton spectrum. This technique requires particular targets and a high resolution proton detector. Therefore thin gold foils with a microgrooved rear side were manufactured and characterized. Calibrated GafChromic radiochromic film (RCF) types MD-55, HS, and HD-810 in stack configuration were used as spatial and energy resolved film detectors. The principle of the RCF imaging spectroscopy was demonstrated at four different laser systems. This can be a method to characterize a laser system with respect to its proton-acceleration capability. In addition, an algorithm to calculate the spatial and energy resolved proton distribution has been developed and tested to get a better idea of laser-accelerated proton beams and their energy deposition with respect to further applications.

Development and calibration of a Thomson parabola with microchannel plate for the detection of laser-accelerated MeV ions.

This article reports on the development and application of a Thomson parabola (TP) equipped with a (90x70) mm(2) microchannel-plate (MCP) for the analysis of laser-accelerated ions, produced by a high-energy, high-intensity laser system. The MCP allows an online measurement of the produced ions in every single laser shot. An electromagnet instead of permanent magnets is used that allows the tuning of the magnetic field to adapt the field strength to the analyzed ion species and energy. We describe recent experiments at the 100 TW laser facility at the Laboratoire d'Utilization des Lasers Intenses (LULI) in Palaiseau, France, where we have observed multiple ion species and charge states with ions accelerated up to 5 MeV/u (O(+6)), emitted from the rear surface of a laser-irradiated 50 microm Au foil. Within the experiment the TP was calibrated for protons and for the first time conversion efficiencies of MeV protons (2-13 MeV) to primary electrons (electrons immediately generated by an ion impact onto a surface) in the MCP are presented.

Controlled transport and focusing of laser-accelerated protons with miniature magnetic devices.

This Letter demonstrates the transporting and focusing of laser-accelerated 14 MeV protons by permanent magnet miniature quadrupole lenses providing field gradients of up to 500 T/m. The approach is highly reproducible and predictable, leading to a focal spot of (286 x 173) microm full width at half maximum 50 cm behind the source. It decouples the relativistic laser-proton acceleration from the beam transport, paving the way to optimize both separately. The collimation and the subsequent energy selection obtained are perfectly applicable for upcoming high-energy, high-repetition rate laser systems.

Enhancement of innate and cell-mediated immunity by antimycobacterial antibodies.

We investigated the ability of human antibodies induced by Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccination to protect against mycobacterial infections. Serum samples containing mycobacterium-specific antibodies were obtained from volunteers who had received two intradermal BCG vaccinations 6 months apart. Significant increases in lipoarabinomannan (LAM)-specific immunoglobulin G (IgG) were detected after both the primary and booster vaccinations. Effects of mycobacterium-specific antibodies on surface binding and internalization of BCG by neutrophils and monocytes/macrophages were studied, using green fluorescent protein (gfp)-expressing BCG. Surface-bound gfp-expressing BCG were distinguished from intracellular BCG by surface labeling with LAM-specific monoclonal antibody. Internalization of BCG by phagocytic cells was shown to be significantly enhanced in postvaccination serum samples. Furthermore, the inhibitory effects of neutrophils and monocytes/macrophages on mycobacterial growth were significantly enhanced by BCG-induced antibodies. The growth-inhibiting effects of postvaccination sera were reversed by preabsorption of IgG with Protein G. Finally, the helper effects of antimycobacterial antibodies for the induction of cell-mediated immune responses were investigated. BCG-induced antibodies significantly enhanced proliferation and gamma interferon production in mycobacterium-specific CD4(+) and CD8(+) T cells, as well as the proportion of proliferating and degranulating CD8(+) T cells. We conclude that mycobacterium-specific antibodies are capable of enhancing both innate and cell-mediated immune responses to mycobacteria.

Comparison of laser ion acceleration from the front and rear surfaces of thin foils.

The comparative efficiency and beam characteristics of high-energy ions generated by high-intensity short-pulse lasers (approximately 1-6 x 10(19) W/cm2) from both the front and rear surfaces of thin metal foils have been measured under identical conditions. Using direct beam measurements and nuclear activation techniques, we find that rear-surface acceleration produces higher energy particles with smaller divergence and a higher efficiency than front-surface acceleration. Our observations are well reproduced by realistic particle-in-cell simulations, and we predict optimal criteria for future applications.

Ultralow emittance, multi-MeV proton beams from a laser virtual-cathode plasma accelerator.

The laminarity of high-current multi-MeV proton beams produced by irradiating thin metallic foils with ultraintense lasers has been measured. For proton energies >10 MeV, the transverse and longitudinal emittance are, respectively, <0.004 mm mrad and <10(-4) eV s, i.e., at least 100-fold and may be as much as 10(4)-fold better than conventional accelerator beams. The fast acceleration being electrostatic from an initially cold surface, only collisions with the accelerating fast electrons appear to limit the beam laminarity. The ion beam source size is measured to be <15 microm (FWHM) for proton energies >10 MeV.