Demonstration of a Circularly Polarized Plasma-Based Soft-X-Ray Laser.

We report the first experimental demonstration of a laser-driven circularly polarized soft-x-ray laser chain. It has been achieved by seeding a 32.8 nm Kr ix plasma amplifier with a high-order harmonic beam, which has been circularly polarized using a four-reflector polarizer. Our measurements testify that the amplified radiation maintains the initial polarization of the seed pulse in good agreement with our Maxwell-Bloch modeling. The resulting fully circular soft-x-ray laser beam exhibits a Gaussian profile and yields about 10^{10} photons per shot, fulfilling the requirements for laboratory-scale photon-demanding application experiments.

Angular-momentum evolution in laser-plasma accelerators.

The transverse properties of an electron beam are characterized by two quantities, the emittance which indicates the electron beam extent in the phase space and the angular momentum which allows for nonplanar electron trajectories. Whereas the emittance of electron beams produced in a laser-plasma accelerator has been measured in several experiments, their angular momentum has been scarcely studied. It was demonstrated that electrons in a laser-plasma accelerator carry some angular momentum, but its origin was not established. Here we identify one source of angular-momentum growth and we present experimental results showing that the angular-momentum content evolves during the acceleration.

Single shot phase contrast imaging using laser-produced Betatron x-ray beams.

Development of x-ray phase contrast imaging applications with a laboratory scale source have been limited by the long exposure time needed to obtain one image. We demonstrate, using the Betatron x-ray radiation produced when electrons are accelerated and wiggled in the laser-wakefield cavity, that a high-quality phase contrast image of a complex object (here, a bee), located in air, can be obtained with a single laser shot. The Betatron x-ray source used in this proof of principle experiment has a source diameter of 1.7 µm and produces a synchrotron spectrum with critical energy E(c)=12.3±2.5 keV and 109 photons per shot in the whole spectrum.

Controlled betatron x-ray radiation from tunable optically injected electrons.

The features of Betatron x-ray emission produced in a laser-plasma accelerator are closely linked to the properties of the relativistic electrons which are at the origin of the radiation. While in interaction regimes explored previously the source was by nature unstable, following the fluctuations of the electron beam, we demonstrate in this Letter the possibility to generate x-ray Betatron radiation with controlled and reproducible features, allowing fine studies of its properties. To do so, Betatron radiation is produced using monoenergetic electrons with tunable energies from a laser-plasma accelerator with colliding pulse injection [J. Faure et al., Nature (London) 444, 737 (2006)]. The presented study provides evidence of the correlations between electrons and x-rays, and the obtained results open significant perspectives toward the production of a stable and controlled femtosecond Betatron x-ray source in the keV range.

Mapping the x-ray emission region in a laser-plasma accelerator.

The x-ray emission in laser-plasma accelerators can be a powerful tool to understand the physics of relativistic laser-plasma interaction. It is shown here that the mapping of betatron x-ray radiation can be obtained from the x-ray beam profile when an aperture mask is positioned just beyond the end of the emission region. The influence of the plasma density on the position and the longitudinal profile of the x-ray emission is investigated and compared to particle-in-cell simulations. The measurement of the x-ray emission position and length provides insight on the dynamics of the interaction, including the electron self-injection region, possible multiple injection, and the role of the electron beam driven wakefield.

Coherence-based transverse measurement of synchrotron x-ray radiation from relativistic laser-plasma interaction and laser-accelerated electrons.

We observe Fresnel edge diffraction of the x-ray beam generated by the relativistic interaction of a high-intensity laser pulse with He gas. The observed diffraction at center energy 4.5 keV agrees with Gaussian incoherent source profile of full-width-half-maximum (FWHM) < 8 microm. Analysis indicates this corresponds to an upper limit on the transverse profile of laser-accelerated electrons within the plasma in agreement with three-dimensional, particle-in-cell results (FWHM = 4 microm).

Influence of Bcl-2 overexpression on the ceramide pathway in daunorubicin-induced apoptosis of leukemic cells.

We have previously demonstrated that daunorubicin (DNR) induces apoptosis in some leukemic myeloid cell lines. We investigated a potential protective role for Bcl-2 in apoptosis induced by DNR in two leukemic cell lines, one myeloid and one lymphoid, overexpressing the anti-apoptotic gene Bcl-2. Parental cells treated with DNR exhibited classical features of apoptosis 6 h after drug exposure, all the cells being dead after 30-48 h. In contrast, overexpression of Bcl-2 significantly delayed, but did not prevent the occurrence of DNR-induced apoptosis, with no surviving cells 96 h after drug exposure. To elucidate the mechanism of the protection mediated by Bcl-2, we explored the signaling pathway which initiates DNR-induced apoptosis. In this report, we show that, in both the myeloid and lymphoid parental cell lines, DNR triggered a sphingomyelin (SM) hydrolysis after 10-15 min with a concomitant ceramide generation. Moreover, exogenous ceramide induced DNA fragmentation in these cells, with levels similar to those observed with DNR treatment. In contrast, Bcl-2 overexpression protected the cells against apoptosis induced by ceramide treatment, without preventing the early SM hydrolysis nor the ceramide generation in these cells. Our results strongly suggest that Bcl-2-mediated protection of DNR-induced apoptosis is effected downstream of the SM-ceramide signaling pathway.

Demonstration of relativistic electron beam focusing by a laser-plasma lens.

Laser-plasma technology promises a drastic reduction of the size of high-energy electron accelerators. It could make free-electron lasers available to a broad scientific community and push further the limits of electron accelerators for high-energy physics. Furthermore, the unique femtosecond nature of the source makes it a promising tool for the study of ultrafast phenomena. However, applications are hindered by the lack of suitable lens to transport this kind of high-current electron beams mainly due to their divergence. Here we show that this issue can be solved by using a laser-plasma lens in which the field gradients are five order of magnitude larger than in conventional optics. We demonstrate a reduction of the divergence by nearly a factor of three, which should allow for an efficient coupling of the beam with a conventional beam transport line.

The phosphoinositide 3-kinase/Akt pathway is activated by daunorubicin in human acute myeloid leukemia cell lines.

Daunorubicin induces apoptosis in myeloid leukemia cells by activation of neutral sphingomyelinase and ceramide generation occurring 4-10 min after daunorubicin addition. We show here that daunorubicin is able to increase the phosphoinositide 3-kinase activity and enhance intracellular phosphoinositide 3-kinase lipid products prior to ceramide generation. Daunorubicin activates Akt, a downstream phosphoinositide 3-kinase effector. Interestingly, the phosphoinositide 3-kinase inhibitors wortmannin and LY294002 accelerate daunorubicin-induced apoptosis in U937 cells. The phosphoinositide 3-kinase/Akt pathway has been involved in cell survival following serum deprivation, tumor necrosis factor alpha, anti-Fas and UV radiations. Our results suggest that anti-tumor agents such as daunorubicin may also activate anti-apoptotic signals that could contribute to drug resistance.

Clinical and histological kidney involvement in human kala-azar.

A 19-year-old women developed prolonged fever, weight loss, hepatosplenomegaly, anemia, leukopenia, and hyperglobulinemia. Appropriate tests indicated that she had visceral leishmaniasis (kala-azar). Urinalysis demonstrated significant proteinuria and microhematuria with the presence of red cell casts. A kidney biopsy was performed. Light microscopy showed a slight mesangial thickening and segmental mesangial proliferation. Immunofluorescence demonstrated deposits of immunoglobulins A and M, complement, and fibrinogen. Electron microscopy showed subendothelial and intramembranous deposits. After treatment with N-methylglucamine antimonate the proteinuria and microhematuria disappeared and the patient recovered uneventfully.

High-energy electron beam production by femtosecond laser interactions with exploding-foil plasmas.

The interaction of an ultraintense, 30-fs laser pulse with a preformed plasma was investigated as a method of producing a beam of high-energy electrons. We used thin foil targets that are exploded by the laser amplified spontaneous emission preceding the main pulse. Optical diagnostics show that the main pulse interacts with a plasma whose density is well below the critical density. By varying the foil thickness, we were able to obtain a substantial emission of electrons in a narrow cone along the laser direction with a typical energy well above the laser ponderomotive potential. These results are explained in terms of wake-field acceleration.

Observation of longitudinal and transverse self-injections in laser-plasma accelerators.

Laser-plasma accelerators can produce high-quality electron beams, up to giga electronvolts in energy, from a centimetre scale device. The properties of the electron beams and the accelerator stability are largely determined by the injection stage of electrons into the accelerator. The simplest mechanism of injection is self-injection, in which the wakefield is strong enough to trap cold plasma electrons into the laser wake. The main drawback of this method is its lack of shot-to-shot stability. Here we present experimental and numerical results that demonstrate the existence of two different self-injection mechanisms. Transverse self-injection is shown to lead to low stability and poor-quality electron beams, because of a strong dependence on the intensity profile of the laser pulse. In contrast, longitudinal injection, which is unambiguously observed for the first time, is shown to lead to much more stable acceleration and higher-quality electron beams.

Small atomic displacements recorded in bismuth by the optical reflectivity of femtosecond laser-pulse excitations.

Subtle atomic motion in a Bi crystal excited by a 35 fs-laser pulse has been recovered from the transient reflectivity of an optical probe measured with an accuracy of 10(-5). Analysis shows that a novel effect reported here-an initial negative drop in reflectivity-relates to a delicate coherent displacement of atoms by the polarization force during the pulse. We also show that reflectivity oscillations with a frequency coinciding with that of cold Bi are related to optical phonons excited by the electron temperature gradient through electron-phonon coupling.

Observation of synchrotron radiation from electrons accelerated in a petawatt-laser-generated plasma cavity.

The dynamics of plasma electrons in the focus of a petawatt laser beam are studied via measurements of their x-ray synchrotron radiation. With increasing laser intensity, a forward directed beam of x rays extending to 50 keV is observed. The measured x rays are well described in the synchrotron asymptotic limit of electrons oscillating in a plasma channel. The critical energy of the measured synchrotron spectrum is found to scale as the Maxwellian temperature of the simultaneously measured electron spectra. At low laser intensity transverse oscillations are negligible as the electrons are predominantly accelerated axially by the laser generated wakefield. At high laser intensity, electrons are directly accelerated by the laser and enter a highly radiative regime with up to 5% of their energy converted into x rays.

X-ray radiation from nonlinear Thomson scattering of an intense femtosecond laser on relativistic electrons in a helium plasma.

We have generated x-ray radiation from the nonlinear Thomson scattering of a 30 fs/1.5 J laser beam on plasma electrons. A collimated x-ray radiation with a broad continuous spectrum peaked at 0.15 keV with a significant tail up to 2 keV has been observed. These characteristics are found to depend strongly on the laser strength parameter a(0). This radiative process is dominant for a(0) greater than unity at which point the relativistic scattering of the laser light originates from MeV energy electrons inside the plasma.

Daunorubicin-induced apoptosis: triggering of ceramide generation through sphingomyelin hydrolysis.

The nature of the signaling pathway(s) which initiate drug-triggered apoptosis remains largely unknown and is of fundamental importance in understanding cell death induced by chemotherapeutic agents. Here we show that in the leukemic cell lines U937 and HL-60, daunorubicin, at concentrations which trigger apoptosis, stimulated two distinct cycles of sphingomyelin hydrolysis (approximately 20% decrease at 1 microM) within 4-10 min and 60-75 min with concomitant ceramide generation. We demonstrate that the increase in ceramide levels, which precedes apoptosis, is mediated by a neutral sphingomyelinase and not by ceramide synthase. Indeed, potent ceramide synthase inhibitors such as fumonisin B1 did not affect daunorubicin-triggered sphingomyelin hydrolysis, ceramide generation or apoptosis. In conclusion, we provide evidence that daunorubicin-triggered apoptosis is mediated by a signaling pathway which is initiated by an early sphingomyelin-derived ceramide production.

Frequency-domain interferometer for measuring the phase and amplitude of a femtosecond pulse probing a laser-produced plasma.

A frequency-domain interferometer for probing the variations of the dielectric constant of a plasma with sub-100- fs temporal resolution and lambda/2000 phase resolution is described. Imaging the plasma on the entrance slit of a spectrograph provides spatial resolution along a diameter of the focal spot. The technique is used to map out the expansion of the critical density surface of a femtosecond laser-produced plasma with subnanometer spatial resolution along the laser axis.

Global optimization of high harmonic generation.

We investigate the relevance of the absorption limit concept in the optimization of high harmonic generation. Thanks to the first direct observation of the coherence length of the process from high-contrast Maker fringes, we unravel experimental conditions for which the harmonic dipole response is enhanced when phase matching is realized within the absorption limit, leading to record conversion efficiencies in argon. Moreover, we show that harmonic generation in guided or freely propagating geometries are equivalent in the loose focusing regime. This analysis is generalized to other advanced phase-matching schemes, thereby predicting the possibility to boost the conversion efficiencies using light noble gases.

Non-thermal melting in semiconductors measured at femtosecond resolution.

Ultrafast time-resolved optical spectroscopy has revealed new classes of physical, chemical and biological reactions, in which directed, deterministic motions of atoms have a key role. This contrasts with the random, diffusive motion of atoms across activation barriers that typically determines kinetic rates on slower timescales. An example of these new processes is the ultrafast melting of semiconductors, which is believed to arise from a strong modification of the inter-atomic forces owing to laser-induced promotion of a large fraction (10% or more) of the valence electrons to the conduction band. The atoms immediately begin to move and rapidly gain sufficient kinetic energy to induce melting--much faster than the several picoseconds required to convert the electronic energy into thermal motions. Here we present measurements of the characteristic melting time of InSb with a recently developed technique of ultrafast time-resolved X-ray diffraction that, in contrast to optical spectroscopy, provides a direct probe of the changing atomic structure. The data establish unambiguously a loss of long-range order up to 900 A inside the crystal, with time constants as short as 350 femtoseconds. This ability to obtain the quantitative structural characterization of non-thermal processes should find widespread application in the study of ultrafast dynamics in other physical, chemical and biological systems.