Dynamics of Nanosecond Laser Pulse Propagation and of Associated Instabilities in a Magnetized Underdense Plasma.

The propagation and energy coupling of intense laser beams in plasmas are critical issues in inertial confinement fusion. Applying magnetic fields to such a setup has been shown to enhance fuel confinement and heating. Here we report on experimental measurements demonstrating improved transmission and increased smoothing of a high-power laser beam propagating in a magnetized underdense plasma. We also measure enhanced backscattering, which our kinetic simulations show is due to magnetic confinement of hot electrons, thus leading to reduced target preheating.

[Leptospirosis: A growing health threat to fish farming and recreational activities]. / La leptospirose : une menace sanitaire croissante pour les activités piscicoles et récréatives.

Leptospirosis is a cosmopolitan infectious disease caused by the bacteria Leptospirainterrogans, which is worldwide increasing as the result of climate changes favoring the reproduction of asymptomatic reservoir rodents and also flooding that brings mammals and humans into contact with contaminated water. This disease affects many mammals among wild, domestic or farmed animals. In humans, it is manifested through frustrated to severe forms that can lead to liver and kidney failure and death in about one in ten severe cases. Diagnostic methods and treatments are satisfactory. Prophylaxis is based on individual protective measures including vaccination. The single human vaccine that is available is expensive and it protects 97% against about a third of human pathogenic serovars. Moreover, this vaccine is not covered by health insurance. Better epidemiological knowledge, particularly at European level, could stimulate research in this area in order to obtain a vaccine that would protect more comprehensively against serovars pathogenic to humans.

Crystal growth, spectroscopy and laser performances of Pr3+:Sr0.7La0.3Mg0.3Al11.7O19 (Pr:ASL).

We report on the crystal growth, spectroscopic properties and visible laser performances of Pr3+-doped Sr0.7La0.3Mg0.3Al11.7O19 (ASL). ASL crystals doped with 2 at.% and 4 at.% Pr3+ were grown by Czochralski method. The laser experiments were carried out in a plane-concave resonator under excitation at 486 nm, provided from a 2ω-OPSL. Efficient laser emission was obtained with an 8 mm long sample of Pr(2at.%):ASL. The maximum output power amounted to 267 mW, 52 mW, and 318 mW at an absorbed power of 1.2W for red, orange, and deep red emission, respectively.

Spatial and Transient Effects during the Amplification of a Picosecond Pulse Beam by a Nanosecond Pump.

Amplification of a picosecond pulse beam by a lower intensity nanosecond pulse beam was experimentally observed in a flowing plasma. Modifications of intensity distributions in beam focal spots due to nonhomogeneous energy transfer and its transient regime were investigated. The mean transferred power reached 57% of the incident power of the nanosecond pulse beam. An imaging diagnostic allowed the intensity profile of the picosecond pulse beam to be determined, bringing to evidence the spatial nonuniformity of energy transfer in the amplified beam. This diagnostic also enabled us to observe the temporal evolution of the speckle intensity distribution because of the transfer. These results are reproduced by numerical simulations of two complementary codes. The method and the observed effects are important for the understanding of experiments with multiple crossing laser beams in plasmas.

Experimental Investigation of the Collective Raman Scattering of Multiple Laser Beams in Inhomogeneous Plasmas.

Experiments have been performed evidencing significant stimulated Raman sidescattering (SRS) at large angles from the density gradient. This was achieved in long scale-length high-temperature plasmas in which two beams couple to the same scattered electromagnetic wave further demonstrating for the first time this multiple-beam collective SRS interaction. The collective nature of the coupling and the amplification at large angles from the density gradient increase the global SRS losses and produce light scattered in novel directions out of the planes of incidence of the beams. These findings obtained in plasmas conditions relevant of inertial confinement fusion experiments similarly apply to the more complex geometry of these experiments where anomalously large levels of SRS were measured.

New heterocyclic compounds: Synthesis and antitrypanosomal properties.

Three new series of quinoline, quinolone, and benzimidazole derivatives were synthesized and evaluated in vitro against Trypanosoma brucei gambiense. In the quinoline series, the metallo antimalarial drug candidate (ferroquine, FQ) and its ruthenium analogue (ruthenoquine, RQ, compound 13) showed the highest in vitro activities with IC50 values around 0.1 µM. Unfortunately, both compounds failed to cure Trypanosoma brucei brucei infected mice in vivo. The other heterocyclic compounds were active in vitro with IC50 values varying from 0.8 to 34 µM. One of the most interesting results was a fluoroquinolone derivative (compound 2) that was able to offer a survival time of 8 days after a treatment at the single dose of 100 µmol/kg by intraperitoneal route. Although no clear-cut structure-activity relationships emerged, further pharmacomodulations are worth to be developed in this series.

HLA phenotypes of candidates for HSCT: comparing transplanted versus non-transplanted candidates, resulting in the predictive estimation of the probability to find a 10/10 HLA matched donor.

In order to study the impact of human leucocyte antigen (HLA) polymorphism distribution in identifying a matched haematopoietic stem cells unrelated donor (UD), we performed a multi-centric retrospective analysis with the aim of comparing the HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 phenotypes of 2126 patients (772 patients for whom a donor search failed to identify a matched UD, and 1354 patients who received a 10/10 allele level matched UD). Our results showed that rare HLA-C is often responsible for difficulty in identifying a donor. This locus may add a degree of complexity to a supposed 'frequent' HLA-A HLA-B and HLA-DRB1 phenotype, turning this phenotype into a less frequent one. For example, 32.5% of the phenotypes in the non-transplanted patients could not be explained by any of the pairs of known HLA-A, HLA-B, HLA-C and HLA-DRB1 haplotypes while this percentage dropped to less than 2% if combinations of only HLA-A, HLA-B and HLA-DRB1 haplotypes were considered. Such situations can be anticipated by computing an index, based on HLA haplotype frequency, the average registry sample size (ARS). ARS is defined as the inverse of the phenotype frequency computed using all corresponding pairs of haplotype frequencies. ARS confirmed that the most significant difference between transplanted and non-transplanted patients was correlated with the introduction of the locus HLA-C in the analysis (median: 8.3e + 4 vs 3.1e + 6, P < 0.0001). The higher the ARS the lower the likelihood of finding a 10/10 match UD reflecting the rareness of the patient's HLA. The area under receiver operator characteristics (AUROC) values of the ARS computation for HLA-A, HLA-B and HLA-DRB1 was 0.82 (0.80; 0.84) at a low-resolution level (two digits). Overall, our study promotes the use of haplotype frequency-based computations to develop computer-assisted donor search.

[Impact of anti-HLA antibodies on outcomes of allogeneic stem cell transplantation: a report by the SFGM-TC]. / Impact des anticorps anti-HLA sur le devenir de l'allogreffe de cellules souches hématopoïétiques : un rapport par la SFGM-TC.

The role of anti-HLA antibodies in allogeneic stem cell transplantation setting is still unclear. In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC) set up its fourth annual series of workshops which brought together practitioners from all of its member centers. These workshops took place in September 2013 in Lille. This article offers the recommendations of the group that considered the impact that have anti-HLA antibodies on outcomes in allogeneic stem cell transplantation.

Nonlinear kinetic estimate of Raman reflectivity in a hohlraum plasma with a radiation hydrodynamics code.

In this Letter, we introduce an inline model for stimulated Raman scattering (SRS), which runs on our radiation hydrodynamics code troll. This model accounts for nonlinear kinetic effects and for the SRS feedback on the plasma hydrodynamics. We dubbed it PIEM because it is a fully "PredIctivE Model," because no free parameter is to be adjusted a posteriori in order to match the experimental results. PIEM predictions are compared against experimental measurements performed at the Ligne d'Intégration Laser. From these comparisons, we discuss the PIEM ability to correctly catch the impact of nonlinear kinetic effects on SRS.

Antiprotozoal activity of ferroquine.

Ferroquine (FQ, SSR97193) is a synthetic compound currently in development for the treatment of malaria. The use of a single compound to treat several parasitoses would be very convenient for multi-infected patients and also for financial considerations. In this work, the activity of FQ was investigated on three other Protista parasites: Kinetoplastidae (Leishmania and Trypanosoma) and the cosmopolite parasite Trichomonas vaginalis. FQ exhibited a significant in vitro activity on Trypanosoma brucei brucei and Trypanosoma brucei gambiense, the agents of African trypanosomiasis in a range from 0.2 to 3.1 µM. In vivo, intraperitoneally administered FQ demonstrated a weak but significant trypanocidal activity at 100 µmol/kg, which is however higher than the maximum tolerated dose. The drop of the parasitemia of the treated mice was significantly related to the amount of injected FQ. Furthermore, this organometallic compound was responsible for a delay in the appearance of bloodstream parasites at 50 µmol/kg. However, it was not able to cure infected mice. Although no synergy was identified in vitro between FQ and pentamidine, these results justify further investigations by evaluating analogues in this chemical series.

Influence of a random phase plate on the growth of the backward stimulated Brillouin scatter.

We derive the analytical dispersion relation of a high-energy laser beam's backward stimulated Brillouin scattering (BSBS) in a hot plasma, that accounts both for the random phase plate (RPP) induced spatial shaping and its associated phase randomness. Indeed, phase plates are mandatory in large laser facilities where a precise control of the focal spot size is required. While the focal spot size is well controlled, such techniques produce small scale intensity variations that can trigger laser-plasma instabilities such as BSBS. Quantifying the resulting instability variability is shown to be crucial for understanding accurately the backscattering temporal and spatial growth as well as the asymptotic reflectivity. Our model, validated by means of a large number of three-dimensional paraxial simulations and experimental data, offers three quantitative predictions. The first one addresses the temporal exponential growth of the reflectivity by deriving and solving the BSBS RPP dispersion relation. A large statistical variability of the temporal growth rate is shown to be directly related to the phase plate randomness. Then, we predict the portion of the beam's section that is absolutely unstable, thus helping to precisely assess the validity of the vastly used convective analysis. Finally, a simple analytical correction to the plane wave spatial gain is extracted from our theory giving a practical and effective asymptotic reflectivity prediction that includes the impact of phase plates smoothing techniques. Hence, our study sheds light on the long-time studied BSBS, deleterious to many high-energy experimental studies related to the physics of inertial confinement fusion.

Femtosecond Yb:CaGdAlO4 thin-disk oscillator.

A mode-locked thin-disk laser based on Yb:CALGO is demonstrated for the first time. At an average output power of 28 W we obtained pulses with a duration of 300 fs and a pulse energy of 1.3 µJ. 197 fs pulses with 0.9 µJ of energy were achieved at an average output power of 20 W. The shortest pulse duration measured in our experiments was 135 fs with a spectrum centered at 1043 nm. The experiments also revealed a very broad tunability from 1032 to 1046 nm with sub-200 fs pulses.

Experiment in planar geometry for shock ignition studies.

The capacity to launch a strong shock wave in a compressed target in the presence of large preplasma has been investigated experimentally and numerically in a planar geometry. The experiment was performed on the LULI 2000 laser facility using one laser beam to compress the target and a second to launch the strong shock simulating the intensity spike in the shock ignition scheme. Thanks to a large set of diagnostics, it has been possible to compare accurately experimental results with 2D numerical simulations. A good agreement has been observed even if a more detailed study of the laser-plasma interaction for the spike is necessary in order to confirm that this scheme is a possible alternative for inertial confinement fusion.

Identification of phospholipid species affected by miltefosine action in Leishmania donovani cultures using LC-ELSD, LC-ESI/MS, and multivariate data analysis.

Leishmaniasis is a widespread parasitic disease principally treated by intravenous drugs. Hexadecylphosphocholine (miltefosine) has recently proved its efficacy by oral route. Although its mechanism of action has been investigated, and principally relies on perturbations of the metabolism of lipids and especially phospholipids, further studies need to be conducted to detect precisely which metabolic pathways are impacted. For this purpose, the present work proposes a complete lipidomic study focused on membrane phospholipids of clones of Leishmania donovani non-treated (NT), treated (T) and resistant (R) to miltefosine. Firstly, a separation of phospholipids in normal phase high-performance liquid chromatography (NP-HPLC) was coupled to a mass spectrometer (MS) equipped with an electrospray (ESI) ion source, and response was compared to evaporative light scattering detection (ELSD). Secondly, a quantification of phospholipid classes was performed using NP-HPLC/ESI/MS on NT, T and R clones of L. donovani. Thirdly, full-scan acquisitions of analyzed samples were compared using orthogonal signal correction-partial least square-discriminant analysis (OSC-PLS-DA) to highlight phospholipid molecular species of interest between the three types of clones. Structural determination of the most relevant species has finally been performed using tandem mass spectrometry. A first hypothesis on the effect of miltefosine on lipid metabolic pathways is then proposed.

In vitro antileishmanial and antitrypanosomal activities of five medicinal plants from Burkina Faso.

After ethnobotanical surveys in central and western regions of Burkina Faso, five plants namely Lantana ukambensis (Verbenaceae), Xeoderris sthulmannii (Fabaceae), Parinari curatellifollia (Chrysobalanaceae), Ozoroa insignis (Anacardiaceae), and Ficus platyphylla (Moraceae) were selected for their traditional use in the treatment of parasitic diseases and cancer. Our previous studies have focused on the phytochemical, genotoxicity, antioxidant, and antiproliferative activities of these plants. In this study, the methanol extract of each plant was tested to reveal probable antileishmanial and antitrypanosomal activities. Colorimetric and spectrophotometric methods were used for the detection of antileishmanial and antitrypanosomal activities. Leishmania donovani (LV9 WT) and Trypanosoma brucei brucei GVR 35 were used to test the antileishmanial and antitrypanosomal activities, respectively. All extracts of tested plants showed a significant antitrypanosomal activity with minimum lethal concentrations between 1.5 and 25 µg/ml, the L. ukambensis extract being the most active. In the antileishmanial test, only the extract from L. ukambensis showed significant activity with an inhibitory concentration (IC(50)) of 6.9 µg/ml. The results of this study contribute to the promotion of traditional medicine products and are preliminary for the isolation of new natural molecules for the treatment of leishmaniasis and trypanosomiasis.

In silico analysis of a therapeutic target in Leishmania infantum: the guanosine-diphospho-D-mannose pyrophosphorylase.

Leishmaniases are tropical and sub-tropical diseases for which classical drugs (i.e. antimonials) exhibit toxicity and drug resistance. Such a situation requires to find new chemical series with antileishmanial activity. This work consists in analyzing the structure of a validated target in Leishmania: the GDP-mannose pyrophosphorylase (GDP-MP), an enzyme involved in glycosylation and essential for amastigote survival. By comparing both human and L. infantum GDP-MP 3D homology models, we identified (i) a common motif of amino acids that binds to the mannose moiety of the substrate and, interestingly, (ii) a motif that is specific to the catalytic site of the parasite enzyme. This motif could then be used to design compounds that specifically inhibit the leishmanial GDP-MP, without any effect on the human homolog.

Cylindrical implosion platform for the study of highly magnetized plasmas at Laser MegaJoule.

Investigating the potential benefits of the use of magnetic fields in inertial confinement fusion experiments has given rise to experimental platforms like the Magnetized Liner Inertial Fusion approach at the Z-machine (Sandia National Laboratories) or its laser-driven equivalent at OMEGA (Laboratory for Laser Energetics). Implementing these platforms at MegaJoule-scale laser facilities, such as the Laser MegaJoule (LMJ) or the National Ignition Facility (NIF), is crucial to reaching self-sustained nuclear fusion and enlarges the level of magnetization that can be achieved through a higher compression. In this paper, we present a complete design of an experimental platform for magnetized implosions using cylindrical targets at LMJ. A seed magnetic field is generated along the axis of the cylinder using laser-driven coil targets, minimizing debris and increasing diagnostic access compared with pulsed power field generators. We present a comprehensive simulation study of the initial B field generated with these coil targets, as well as two-dimensional extended magnetohydrodynamics simulations showing that a 5 T initial B field is compressed up to 25 kT during the implosion. Under these circumstances, the electrons become magnetized, which severely modifies the plasma conditions at stagnation. In particular, in the hot spot the electron temperature is increased (from 1 keV to 5 keV) while the density is reduced (from 40g/cm^{3} to 7g/cm^{3}). We discuss how these changes can be diagnosed using x-ray imaging and spectroscopy, and particle diagnostics. We propose the simultaneous use of two dopants in the fuel (Ar and Kr) to act as spectroscopic tracers. We show that this introduces an effective spatial resolution in the plasma which permits an unambiguous observation of the B-field effects. Additionally, we present a plan for future experiments of this kind at LMJ.

Yb:CaGdAlO4 thin-disk laser.

We present the first demonstration of a Yb:CALGO thin-disk laser. In a slightly multimode configuration, we obtained up to 30 W of average power at a slope efficiency of 40% and an optical-to-optical efficiency of 32%. With a single-mode cavity, an average power of 25 W was achieved. A tuning range from 1018 to 1052 nm could be demonstrated by inserting a prism into the cavity. In the Q-switched regime, we obtained 1 mJ of pulse energy at a repetition rate of 100 Hz.

HLA polymorphism in a Guarani-Indian population from Paraguay and its usefulness for the Hispano-Indian admixture study in Paraguay.

In this study we investigated the human leucocyte antigen-A (HLA-A), -B and DRB1 polymorphism of Native American population of Paraguay, the Guarani Indians. We found that the HLA variability consisted of 5 HLA-A, 7 HLA-B and 6 HLA-DRB1 groups of alleles and of several specific alleles (B*1504, B*3505, B*3912, B*4004, B*5104, DRB1*0411, DRB1*1413) common in other Native American populations. The comparison of the HLA polymorphism of the Guaranis from Paraguay with the «Mestizos¼ of Paraguay and the Spaniards showed that the «Mestizos¼ of Paraguay are genetically very distant from the Guarani Indians of Paraguay but much more close to the Spaniards. This can be explained, at least in part, by the history of the country. Our results are of importance in transplantation, in particular in the search for an unrelated donor for a Paraguayan patient requiring hematopoietic stem cell transplantation.

Sitamaquine as a putative antileishmanial drug candidate: from the mechanism of action to the risk of drug resistance.

Sitamaquine is a 8-aminoquinoline in development for the treatment of visceral leishmaniasis by oral route, no activity being observed on the experimental cutaneous leishmaniasis experimental models. Recent data explain how sitamaquine accumulate in Leishmania parasites, however its molecular targets remain to be identified. An advantage of sitamaquine is its short elimination half-life, preventing a rapid resistance emergence. The antileishmanial action of its metabolites is not known. The selection of a sitamaquine-resistant clone of L. donovani in laboratory and the phase II clinical trials pointing out some adverse effects such as methemoglobinemia and nephrotoxicity are considered for a further development decision.