Demonstration of a compact plasma accelerator powered by laser-accelerated electron beams.

Plasma wakefield accelerators are capable of sustaining gigavolt-per-centimeter accelerating fields, surpassing the electric breakdown threshold in state-of-the-art accelerator modules by 3-4 orders of magnitude. Beam-driven wakefields offer particularly attractive conditions for the generation and acceleration of high-quality beams. However, this scheme relies on kilometer-scale accelerators. Here, we report on the demonstration of a millimeter-scale plasma accelerator powered by laser-accelerated electron beams. We showcase the acceleration of electron beams to 128 MeV, consistent with simulations exhibiting accelerating gradients exceeding 100 GV m-1. This miniaturized accelerator is further explored by employing a controlled pair of drive and witness electron bunches, where a fraction of the driver energy is transferred to the accelerated witness through the plasma. Such a hybrid approach allows fundamental studies of beam-driven plasma accelerator concepts at widely accessible high-power laser facilities. It is anticipated to provide compact sources of energetic high-brightness electron beams for quality-demanding applications such as free-electron lasers.

Coherent Optical Signatures of Electron Microbunching in Laser-Driven Plasma Accelerators.

We report observations of coherent optical transition radiation interferometry (COTRI) patterns generated by microbunched ∼200-MeV electrons as they emerge from a laser-driven plasma accelerator. The divergence of the microbunched portion of electrons, deduced by comparison to a COTRI model, is ∼9× smaller than the ∼3 mrad ensemble beam divergence, while the radius of the microbunched beam, obtained from COTR images on the same shot, is <3 µm. The combined results show that the microbunched distribution has estimated transverse normalized emittance ∼0.4 mm mrad.

Hybrid LWFA-PWFA staging as a beam energy and brightness transformer: conceptual design and simulations.

We present a conceptual design for a hybrid laser-driven plasma wakefield accelerator (LWFA) to beam-driven plasma wakefield accelerator (PWFA). In this set-up, the output beams from an LWFA stage are used as input beams of a new PWFA stage. In the PWFA stage, a new witness beam of largely increased quality can be produced and accelerated to higher energies. The feasibility and the potential of this concept is shown through exemplary particle-in-cell simulations. In addition, preliminary simulation results for a proof-of-concept experiment in Helmholtz-Zentrum Dresden-Rossendorf (Germany) are shown. This article is part of the Theo Murphy meeting issue 'Directions in particle beam-driven plasma wakefield acceleration'.

Making spectral shape measurements in inverse Compton scattering a tool for advanced diagnostic applications.

Interaction of relativistic electron beams with high power lasers can both serve as a secondary light source and as a novel diagnostic tool for various beam parameters. For both applications, it is important to understand the dynamics of the inverse Compton scattering mechanism and the dependence of the scattered light's spectral properties on the interacting laser and electron beam parameters. Measurements are easily misinterpreted due to the complex interplay of the interaction parameters. Here we report the potential of inverse Compton scattering as an advanced diagnostic tool by investigating two of the most influential interaction parameters, namely the laser intensity and the electron beam emittance. Established scaling laws for the spectral bandwidth and redshift of the mean scattered photon energy are refined. This allows for a quantitatively well matching prediction of the spectral shape. Driving the interaction to a nonlinear regime, we spectrally resolve the rise of higher harmonic radiation with increasing laser intensity. Unprecedented agreement with 3D radiation simulations is found, showing the good control and characterization of the interaction. The findings advance the interpretation of inverse Compton scattering measurements into a diagnostic tool for electron beams from laser plasma acceleration.

Demonstration of a beam loaded nanocoulomb-class laser wakefield accelerator.

Laser-plasma wakefield accelerators have seen tremendous progress, now capable of producing quasi-monoenergetic electron beams in the GeV energy range with few-femtoseconds bunch duration. Scaling these accelerators to the nanocoulomb range would yield hundreds of kiloamperes peak current and stimulate the next generation of radiation sources covering high-field THz, high-brightness X-ray and γ-ray sources, compact free-electron lasers and laboratory-size beam-driven plasma accelerators. However, accelerators generating such currents operate in the beam loading regime where the accelerating field is strongly modified by the self-fields of the injected bunch, potentially deteriorating key beam parameters. Here we demonstrate that, if appropriately controlled, the beam loading effect can be employed to improve the accelerator's performance. Self-truncated ionization injection enables loading of unprecedented charges of ∼0.5 nC within a mono-energetic peak. As the energy balance is reached, we show that the accelerator operates at the theoretically predicted optimal loading condition and the final energy spread is minimized.Higher beam quality and stability are desired in laser-plasma accelerators for their applications in compact light sources. Here the authors demonstrate in laser plasma wakefield electron acceleration that the beam loading effect can be employed to improve beam quality by controlling the beam charge.

Identifying the linear phase of the relativistic Kelvin-Helmholtz instability and measuring its growth rate via radiation.

For the relativistic Kelvin-Helmholtz instability (KHI), which occurs at shear interfaces between two plasma streams, we report results on the polarized radiation over all observation directions and frequencies emitted by the plasma electrons from ab initio kinetic simulations. We find the polarization of the radiation to provide a clear signature for distinguishing the linear phase of the KHI from its other phases. During the linear phase, we predict the growth rate of the KHI radiation power to match the growth rate of the KHI to a high degree. Our predictions are based on a model of the vortex dynamics, which describes the electron motion in the vicinity of the shear interface between the two streams. Albeit the complex and turbulent dynamics happening in the shear region, we find excellent agreement between our model and large-scale particle-in-cell simulations. Our findings pave the way for identifying the KHI linear regime and for measuring its growth rate in astrophysical jets observable on earth as well as in laboratory plasmas.

High resolution energy-angle correlation measurement of hard x rays from laser-Thomson backscattering.

Thomson backscattering of intense laser pulses from relativistic electrons not only allows for the generation of bright x-ray pulses but also for the investigation of the complex particle dynamics at the interaction point. For this purpose a complete spectral characterization of a Thomson source powered by a compact linear electron accelerator is performed with unprecedented angular and energy resolution. A rigorous statistical analysis comparing experimental data to 3D simulations enables, e.g., the extraction of the angular distribution of electrons with 1.5% accuracy and, in total, provides predictive capability for the future high brightness hard x-ray source PHOENIX (photon electron collider for narrow bandwidth intense x rays) and potential gamma-ray sources.

Electron temperature scaling in laser interaction with solids.

A precise knowledge of the temperature and number of hot electrons generated in the interaction of short-pulse high-intensity lasers with solids is crucial for harnessing the energy of a laser pulse in applications such as laser-driven ion acceleration or fast ignition. Nevertheless, present scaling laws tend to overestimate the hot electron temperature when compared to experiment and simulations. We present a novel approach that is based on a weighted average of the kinetic energy of an ensemble of electrons. We find that the scaling of electron energy with laser intensity can be derived from a general Lorentz invariant electron distribution ansatz that does not rely on a specific model of energy absorption. The scaling derived is in perfect agreement with simulation results and clearly follows the trend seen in recent experiments, especially at high laser intensities where other scalings fail to describe the simulations accurately.

Electron bunch length measurements from laser-accelerated electrons using single-shot THz time-domain interferometry.

Laser-plasma wakefield-based electron accelerators are expected to deliver ultrashort electron bunches with unprecedented peak currents. However, their actual pulse duration has never been directly measured in a single-shot experiment. We present measurements of the ultrashort duration of such electron bunches by means of THz time-domain interferometry. With data obtained using a 0.5 J, 45 fs, 800 nm laser and a ZnTe-based electro-optical setup, we demonstrate the duration of laser-accelerated, quasimonoenergetic electron bunches [best fit of 32 fs (FWHM) with a 90% upper confidence level of 38 fs] to be shorter than the drive laser pulse, but similar to the plasma period.

Estimation and assessment of Mars contamination.

Since the beginning of the exploration of Mars, more than fourty years ago, thirty-six missions have been launched, including fifty-nine different space systems such as fly-by spacecraft, orbiters, cruise modules, landing or penetrating systems. Taking into account failures at launch, about three missions out of four have been successfully sent toward the Red Planet. The fact today is that Mars orbital environment includes orbiters and perhaps debris, and that its atmosphere and its surface include terrestrial compounds and dormant microorganisms. Coming from the UN Outer Space Treaty [United Nations Treaty on Principles Governing the Activities of States in the Exploration and Use of Outer Space, including the Moon and Other Celestial Bodies (the "Outer Space Treaty") referenced 610 UNTS 205 - resolution 2222(XXI) of December 1966] and according to the COSPAR planetary protection policy recommendations [COSPAR Planetary Protection Policy (20 October 2002), accepted by the Council and Bureau, as moved for adoption by SC F and PPP, prepared by the COSPAR/IAU Workshop on Planetary Protection, 4/02 with updates 10/0, 2002], Mars environment has to be preserved so as not to jeopardize the scientific investigations, and the level of terrestrial material brought on and around Mars theoretically has to comply with this policy. It is useful to evaluate what and how many materials, compounds and microorganisms are on Mars, to list what is in orbit and to identify where all these items are. Considering assumptions about materials, spores and gas location and dispersion on Mars, average contamination levels can be estimated. It is clear now that as long as missions are sent to other extraterrestrial bodies, it is not possible to keep them perfectly clean. Mars is one of the most concerned body, and the large number of missions achieved, on-going and planned now raise the question about its possible contamination, not necessarily from a biological point of view, but with respect to all types of contamination. Answering this question, will help to assess the potential effects of such contamination on scientific results and will address concerns relative to any ethical considerations about the contamination of other planets.

Chemists, physicians, and changing perspectives on the scientific revolution.

Positivism in the history of science and medicine was challenged by Walter Pagel more than fifty years ago. He sought to understand early modern figures such as Harvey, Paracelsus, and van Helmont by looking at all their work, including nonscientific material generally ignored by other scholars. Of special importance in the sixteenth and seventeenth centuries was the chemistry found in the writings of Paracelsus and his followers. These "chemical philosophers" offered a new philosophy based on chemistry and chemical analogies that was to replace the works of the ancients. As physicians, they debated first with Galenists and Aristotelians and later with mechanists. The essay argues that these debates were an essential chapter in the development of the Scientific Revolution and important for understanding the Chemical Revolution of the eighteenth century.

Detection of genomic polymorphisms among isolates of the intracellular bacterium Cowdria ruminantium by random amplified polymorphic DNA and Southern blotting.

Sixteen primers were successfully used in a RAPD assay to generate reproducible fingerprints for six isolates of Cowdria ruminantium, a tick-transmitted rickettsia of ruminants. Distinction between stocks was possible by using one or at most two primers. Two stocks were very similar although originating from widely distant geographical regions. A genetic distance tree was constructed by analysing 108 fragments in pairwise comparison between stocks. Three amplification fragments probed with C. ruminantium genomic DNA determined a restriction fragment length polymorphism which allowed the distinction between stocks except for the two stocks that had similar RAPD patterns. The potential of RAPD to determine the extent of genetic diversity of C. ruminantium and to develop probes or PCR primers for diagnostic purposes is discussed.

Development of an in vitro cloning method for Cowdria ruminantium.

Cowdria ruminantium is a tick-borne rickettsia which causes severe disease in ruminants. All studies with C. ruminantium reported so far were carried out with stocks consisting of infective blood collected from reacting animals or from the same stocks propagated in vitro. Cloned isolates are needed to conduct studies on immune response of the host, on genetic diversity of the parasite, and on mechanisms of attenuation and the development of vaccines. A method of cloning based on the particular chlamydia life cycle of Cowdria was developed. Instead of cloning extracellular elementary bodies, it appeared more convenient to clone endothelial cells infected by one morula resulting from the infection of the cell by one elementary body of Cowdria. Two hundred and sixteen clones were obtained by limiting dilution of infected cells. The method was experimentally validated by comparing randomly amplified polymorphic DNA fingerprints from individual clones obtained from endothelial cell cultures coinfected with two different stocks of C. ruminantium.

Enhanced pulmonary accumulation of liposomal amphotericin B (AmBisome) in acute liver transplant failure.

Plasma and tissue concentrations of amphotericin B were determined in a patient treated with liposomal amphotericin B during liver transplant failure. A cumulative rise in amphotericin B plasma concentrations was observed accompanied by an enhanced pulmonary deposition of the drug. Failure of the liver as a major component of the reticuloendothelial system may cause elevated plasma concentrations of liposomal amphotericin B and may consequently enhance deposition of liposomes in the lungs as a substitutive clearing organ.

Pharmacokinetics of liposomal amphotericin B (Ambisome) in critically ill patients.

The liposomal formulation of amphotericin B (AmBisome) greatly reduces the acute and chronic side effects of the parent drug. The present study describes the pharmacokinetic characteristics of AmBisome applied to 10 patients at a dose of 2.8 to 3.0 mg/kg of body weight and compares them to the pharmacokinetics observed in 6 patients treated with amphotericin B deoxycholate at the standard dose of 1.0 mg/kg. Interpatient variabilities of amphotericin B peak concentrations (Cmax) and areas under concentration-time curves (AUC) were 8- to 10-fold greater for patients treated with AmBisome than for patients treated with amphotericin B deoxycholate. At the threefold greater dose of AmBisome, median Cmaxs were 8.4-fold higher (14.4 versus 1.7 microg/ml) and median AUCs exceeded those observed with amphotericin B deoxycholate by 9-fold. This was in part explained by a 5.7-fold lower volume of distribution (0.42 liters/kg) in AmBisome-treated patients. The elimination of amphotericin B from serum was biphasic for both formulations. However, the apparent half-life of elimination was twofold shorter for AmBisome (P = 0.03). Neither hemodialysis nor hemofiltration had a significant impact on AmBisome pharmacokinetics as analyzed in one patient. In conclusion, the liposomal formulation of amphotericin B significantly (P = 0.001) reduces the volume of drug distribution, thereby allowing for greater drug concentrations in serum. The low toxicity of AmBisome therefore cannot readily be explained by its serum pharmacokinetics.

Serum pharmacology of amphotericin B applied in lipid emulsions.

Application of amphotericin B in lipid emulsions (AmB/L) reduced membrane toxicity in vitro and decreased amphotericin B-associated toxic side effects in vivo when compared to that of amphotericin B applied in 5% glucose (AmB/G). Therefore, a comparative analysis of the pharmacological parameters of AmB/L and AmB/G was performed. Thirteen patients were analyzed, and nine of these patients received a subsequent treatment with AmB/G and AmB/L. In patients in both treatment groups amphotericin B showed a biphasic elimination from serum, with a prolonged terminal half-life of approximately 27 h. Patients treated with AmB/L showed significantly lower peak concentrations (44.2%; P = 0.008) and correspondingly lower area under the drug concentration-time curve (AUC) values (64.3%; P = 0.015) compared to the values for the same patients treated with AmB/G at a dose range of 0.6 to 1.5 mg/kg of body weight. The enhanced clearance of AmB/L may be due to a faster initial elimination of amphotericin B-lipid aggregates by the reticuloendothelial system. Lower peak concentrations and AUC values in serum and a correspondingly faster deposition of AmB/L in tissues may at least partly explain the lower toxicity of AmB/L. A comparative pharmacokinetic analysis with data for a single patient treated with AmB/L demonstrated that hemodialysis did not significantly affect the disposition of amphotericin B.

Comparative efficacy of Freund's and Montanide ISA50 adjuvants for the immunisation of goats against heartwater with inactivated Cowdria ruminantium.

Two vaccines, based on inactivated elementary bodies of Cowdria ruminantium, one formulated in Montanide ISA50, the other in Freund's adjuvant, were compared in goats. Administered twice subcutaneously with an interval of 81 days, both protected three out of five goats against a very severe challenge, lethal for all 14 control goats, 3.5 months after the second injection. Both vaccines elicited similar antibody levels. The protection afforded by the Montanide ISA50 vaccine was tested 15 and 17 months after the second injection of the vaccine. Three out of six and five out of six goats, respectively, survived a challenge which killed all four control goats used on each occasion. Antibodies were still detectable in the immunised goats. The level of protection appears to be influenced by the dose of virulent C. ruminantium used for the challenge. As any stock of C. ruminantium can be incorporated in order to cover the antigenic repertoire of the organism, this kind of inactivated vaccine can now be tested in the field.

Planetary protection program for Mars 94/96 mission.

Mars surface in-situ exploration started in 1975 with the American VIKING mission. Two probes landed on the northern hemisphere and provided, for the first time, detailed information on the martian terrain, atmosphere and meteorology. The current goal is to undertake larger surface investigations and many projects are being planned by the major Space Agencies with this objective. Among these projects, the Mars 94/96 mission will make a major contributor toward generating significant information about the martian surface on a large scale. Since the beginning of the Solar System exploration, planets where life could exist have been subject to planetary protection requirements. Those requirements accord with the COSPAR Policy and have two main goals: the protection of the planetary environment from influence or contamination by terrestrial microorganisms, the protection of life science, and particularly of life detection experiments searching extra-terrestrial life, and not life carried by probes and spacecrafts. As the conditions for life and survival for terrestrial microorganisms in the Mars environment became known, COSPAR recommendations were updated. This paper will describe the decontamination requirements which will be applied for the MARS 94/96 mission, the techniques and the procedures which are and will be used to realize and control the decontamination of probes and spacecrafts.

Pharmacokinetics of liposomal amphotericin B (AmBisome) versus other lipid-based formulations.

To lower amphotericin B-associated toxicity, amphotericin B may be integrated into liposomes (AmBisome) or can be administered in Intralipid 20% emulsions (Ampho-B/Lipid). The present study compares the pharmacokinetic characteristics of standard amphotericin B dissolved in glucose 5% (Ampho-B/G) (n = 6) to the alternative formulations Ampho-B/Lipid (n = 8) and Ambisome (n = 10). Ampho-B/G and Ampho-B/Lipid were infused at a dose of 1 mg/kg, while the dose of AmBisome was increased to 3 mg/kg. Infusion duration was 1 h. Pharmacokinetics of Ampho-B/G, AmB/Lipid and AmBisome showed striking differences, specifically with regard to the respective Cmax and AUC values. In fact, after application of AmB/Lipid mean Cmax values were reduced to 39% and mean AUC values were lowered to 57% compared with application of Ampho-B/G in the same patients. This compares with a 1.8-fold greater Vss for Ampho-B/Lipid and a clearance rate which was 2.1-fold faster. By contrast, application of AmBisome (at a three-fold greater dose) resulted in Cmax and AUC values eight-fold and 12-fold greater than those reached by Ampho-B/G. The higher Cmax values achieved by AmBisome relate to a four-fold smaller Vss compared with Ampho-B/G. Assuming a linear relationship between AmBisome dose and Cmax, it was concluded that even at equal doses the liposomal formulation of amphotericin B would result in significantly greater Cmax and AUC values than Ampho-B/G or Ampho-B/Lipid.